key: cord- -cxr ul q authors: cianchi, giovanni; bonizzoli, manuela; pasquini, andrea; bonacchi, massimo; zagli, giovanni; ciapetti, marco; sani, guido; batacchi, stefano; biondi, simona; bernardo, pasquale; lazzeri, chiara; giovannini, valtere; azzi, alberta; abbate, rosanna; gensini, gianfranco; peris, adriano title: ventilatory and ecmo treatment of h n -induced severe respiratory failure: results of an italian referral ecmo center date: - - journal: bmc pulm med doi: . / - - - sha: doc_id: cord_uid: cxr ul q background: since the first outbreak of a respiratory illness caused by h n virus in mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ecmo) assistance in young and often healthy patients. here we describe our experience in h n -induced ards using both ventilation strategy and ecmo assistance. methods: following italian ministry of health instructions, an emergency service was established at the careggi teaching hospital (florence, italy) for the novel pandemic influenza. from sept to jan , all patients admitted to our intensive care unit (icu) of the emergency department with ards due to h n infection were studied. all ecmo treatments were veno-venous. h n infection was confirmed by pcr assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage. lung pathology was evaluated daily by lung ultrasound (lus) examination. results: a total of patients were studied: underwent ecmo treatment, and responded to protective mechanical ventilation. two patients had co-infection by legionella pneumophila. one woman was pregnant. in our series, pcr from bronchoalveolar lavage had a % sensitivity compared to % from pharyngeal swab samples. the routine use of lus limited the number of chest x-ray examinations and decreased transportation to radiology for ct-scan, increasing patient safety and avoiding the transitory disconnection from ventilator. no major complications occurred during ecmo treatments. in three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. overall mortality rate was . %. conclusions: in our experience, early ecmo assistance resulted safe and feasible, considering the life threatening condition, in h n -induced ards. lung ultrasound is an effective mean for daily assessment of ards patients. since the first outbreak of a respiratory illness caused by influenza a (h n ) virus in mexico [ ] , several reports have described the need of intensive care [ ] [ ] [ ] or extracorporeal membrane oxygenation (ecmo) assistance [ ] in young and often healthy patients. beginning august , the italian ministry of health and the tuscany ministry of health issued instructions to identify and establish referral centers able to care for the more severely ill influenza patients. therefore, several referral centers were identified throughout the national territory among the hospitals already experienced in extracorporeal respiratory support techniques. the referral ecmo centres, in addition to being capable of guaranteeing the most advanced treatment in influenza related respiratory failure, were also entrusted with providing support to the nearby hospitals and assuring safe transportation. in the present investigation we report our experience, as an ecmo referral center, in h n -induced acute respiratory distress syndrome (ards) and we present the critical care service planning in response to the h n pandemic. following the instructions of the italian ministry of health and tuscany regional ministry of health, an emergency medical service was established in the careggi hospital in florence italy for the novel pandemic influenza. the careggi hospital ecmo team is composed of: an intensivist, a cardiac surgeon, a cardiologist, a nurse, and a perfusionist. all of the members of the team are properly trained in ecmo treatment. an ambulance and a car are equipped with an ecmo circuit, a transport ventilator and all of the materials needed to initiate extracorporeal support in the peripheral hospitals, and permit safe transportation while on extracorporeal circulation to our referral hospital. the requirement of ecmo was decided based on the italian ministry of health criteria (table ) . from september to january , all patients admitted to our icu with severe respiratory failure due to h n infection were included in this study. patient demographics and clinical characteristics were collected from institutional icu database (filemaker pro, file-maker, inc, usa), from italian group for the evaluation of interventions in intensive care medicine database (giviti margherita project, istituto mario negri, bergamo, italy) and from ecmo national network database. discrete variables are expressed as counts and percentages, whereas continuous variables are reported as medians with th to th interquartile range (iqr). the internal review board approved this retrospective study and informed consent for data publication was obtained from the patients or relatives. pressure volume curves were calculated with ventilator's built in application (draeger evita xl, draeger medical ag, lubeck germany) starting from a peep level of cm h o, with a pressure limit of . ventilation parameters were set on the basis of this calculation, with a peep of cmh o above the lower inflection point of the pressure-volume curve, and a peek pressure below the upper inflection point. in all cases, pressure plateau was limited to cmh o and the tidal volume was kept below ml/kg [ ] . recruitment manoeuvres ( sec at cmh o) were performed twice a day, if needed, to improve pulmonary gas exchange. cannulation was conducted percutaneously with seldinger technique in all cases, and cannulas position was confirmed by transesophageal echocardiography. heparin infusion during extracorporeal lung assistance was monitored every two hours by bedside aptt measurement (hemochron jr. signature plus, itc europe, milan, it), which was maintained between and seconds. in case of renal replacement therapy requirement in ecmo patients, a continuous veno-venous hemodiafiltration circuit was assembled on the ecmo circuit (aspiration on pre-pump line, restitution on preoxygenation line). ecmo patients were ventilated with protective parameters, and respiratory rate and ecmo flow were adjusted to achieve normocarbia and oxygen saturation above %. assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage in accordance with published guidelines [ ] . bronchoalveolar specimens were obtained with a mini-invasive system (kimberly-clark bal cath, kimberly-klark n.v. zaventem -belgium), or by bronchoscopy. patients were isolated in negative pressure atmosphere rooms, and staff wore full protective garments (including ffp respirators, m italia spa, segrate, italy), until consecutive tests were confirmed negative. during the study period only one case of suspected transmission of influenza to a nurse occurred. antiviral therapy consisted in oral oseltamivir ( mg twice daily) and inhaled zanamivir ( mg twice daily). blood and urinary cultures, tracheal aspirate, and pharyngeal swab were obtained upon patient admission. empiric antimicrobial regimen at icu admission was initiated with levofloxacin and amoxicillin/clavulanate; eventually specific antimicrobial therapy was varied or ended on the basis of microbiological results. steroids were administered at low dosage ( mg metilprednisolon twice per day) to prevent lung fibrosis. diuretics were administered at different dosages, depending on clinical judgment and the patient's renal function. lung ultra sound (lus) examinations were daily performed by the attending physician, with a multifrequency convex probe ( . - mhz, mylab tm cv, esaote, genova, it). with the patient in semirecumbent position, lateral and anterior views were obtained from base to apex of the chest. posterior axillary line was followed during lateral transversal examinations. chest quadrants defined by the intercostal spaces and the parasternal, mid-clavicular, and anterior axillary lines were scanned on the anterior chest wall [ ] . the occurrence and extension of parenchymal consolidations, alveolar interstitial syndrome (measured by the number of b-lines), and morphology of pleural line were evaluated [ ] [ ] [ ] . pleural effusions were estimated by using balik's formula [ , ] . in order to ensure a uniform record, and allow to follow the evolution of the findings over time, all exams were recorded in an electronic form, in which the description of the main lus features was predetermined [ ] . during the study period, patients requiring invasive ventilation treatment and/or ecmo were admitted or transferred to our icu. baseline and clinical characteristics of patients admitted for h n -induced severe respiratory failure are summarized in table . the median time between initial, non specific, symptoms and respiratory failure was days (iqr - . ), and severe hypoxia, unresponsiveness to non-invasive ventilation, was the main clinical feature. our patients were young, median age . years, none of them older than years, and eight ( %) younger than . two patients were severely obese (bmi > ), one woman was pregnant ( weeks), two patients had a history of chronic obstructive respiratory disease (copd), and one had diabetes. two patients had legionella pneumophila coinfection at admission, and one young patient ( years old) with suspect viral myocarditis and heart failure. at admission the patients, with the exception of the two coinfected, presented low leukocyte and platelet count and low plasma procalcitonin levels, significant levels of lactate dehydrogenase (ldh), creatine kinase (ck), and c-reactive protein ( table ). median duration of mechanical ventilation (days) was . (iqr . - . ) and median icu length of stay (days) was (iqr - . ). the pregnant woman continued the pregnancy without significant complications. in icu infection rate was low with two ventilator associated pneumonia and two asymptomatic positive blood cultures in two ecmo patients. one ecmo patient died due to a systemic secondary infection by aspergillus: this patient was the only non-surviving patient (overall mortality rate . %). rt-pcrs from bronchoalveolar lavage samples were positive in all patients included in this study. on the contrary, rt-pcr dosed on pharyngeal swab resulted positive in less than % of patients at icu admission, and in % of patients in the second day ( figure ). also efficacy of antiviral therapy was reliably followed through rt-pcr from bronchoalveolar samples, since analysis on pharyngeal swabs became negative quite early. finally, no rt-pcr significant for h n infection from subglottic aspirate sample was found. in one patient, intravenous administration of zanamivir was needed, since the patient remained positive to viral infection after two weeks of therapy. intravenous formulation of zanamivir is still subjected to pre-phase clinical trial investigation, even if some reports on its safety profile are already available in literature. therefore, local ethical committee approval was requested and the manufacturer provided the drug for use. zanamivir was administered intravenously for five days ( mg twice daily), as indicated by the producer. the patient's respiratory function improved and rt-pcr became negative after the third day. no adverse reaction was noted. a total of lus have been performed. during every lus, the following parameters were considered: pleural line aspect and motility, presence of consolidations, occurrence and severity of alveolar interstitial syndrome (based on the number of b-lines), presence of pleural effusion and occurrence of pneumothorax. pleural thickness was described in % of cases and mostly bilaterally. lung base was always involved. lung gliding was present in % of lus, even if decreased ( %). pathological lung pulse was found in % of lus, often in proximity to large parenchyma consolidations. pleural effusion occurred in patients. two spontaneous pneumothorax have been detected with lus during icu treatment. alveolar interstitial syndrome was present in all ultrasound examinations, with the presence of normal lung pattern (spared areas). in % of cases, b-lines were described as moderate/many. at lung recovery, residual b-lines patterns were found mostly at both bases. white lung feature occurred in about % of lus performed, mostly in the anterior and lateral scans. white lung was never uniformly distributed, but it was alternated to spared areas, or areas with a limited number of b-lines. consolidations were found in % of cases. most of them were multiple ( %), and lung bases were always involved. contiguous subpleural consolidations were also present, increasing the pleural thickness laterally, mostly at the base and the apical part. aerial bronchograms were always found within the consolidation pattern. the routine use of lus limited the number of conventional radiology examinations (table ). in ecmo patients group, the higher number of chest x-ray examinations was needed to verify the correct cannulae positioning. in both groups, bedside lus limited the transportation to the ct-scan room, increasing patient safety and avoiding the transitory disconnection of the patient from the ventilator. ecmo was needed in patients (table ). in cases, the ecmo team was alerted and extracorporeal oxygenation was implanted directly at peripheral icus. no major transportation related problems were faced, even in the case of a long distance journey ( km). median duration of ecmo support was days (iqr - . ), with a median duration of mechanical ventilation (days) of (iqr - ). main clinical features and ventilatory and ecmo parameters of patients treated with ecmo are presented in table . bleeding was the most important complication. in three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. three patients presented prolonged oropharyngeal bleeding and transfusions were required. among them, one needed electrical coagulation of a palatine injury, probably related to nursing manoeuvres. two patients presented severe intra-bronchial bleeding, and several flexible bronchoscopy examinations and clot suctions were required. in one of these patients, bleeding from the lower airways during the weaning phase from ecmo, and ecmo removal has been hastened. table summarizes the main differences between patients who underwent to ecmo treatment and patients only ventilated. despite the small sample, ecmo patients clearly showed a higher critical illness score (saps ii), and worst pulmonary gas exchange compared to patients who did not required extracorporeal lung assistance. coinfection and comorbidities at admission were present only in ecmo patients. our study population is young, comprising mainly healthy subjects, as previously reported [ , , ] . risk factors are similar to other studies, such as obesity, diabetes and pregnancy. in the present case series, bacterial infection rate at presentation was low. previous reports showed incidence of secondary superinfection by streptococcus pneumoniae, staphylococcus aureus, pseudomonas aeruginosa, acinetobacter baumannii, escherichia coli [ , , ] . in our experience, we found two cases ( . %) of co-infection with legionella pneumophila, which is, to the best of our knowledge, a new epidemiological data, since no other case has been reported in literature. it is questionable whether legionella pneumophila infection occurred before or after h n pneumonia. however, it could be that h n pneumonia was associated with a lower reactivity of the immune system, as suggested by the low leucocytes count reported in our sample and by other authors [ , , ] . one young patient presented heart failure, and viral myocarditis was suspected. the association of influenza with myocarditis is debated [ ] , and h n related myocarditis, has rarely been reported [ ] . furthermore, in our patient prolonged pre-hospital hypoxia was present and myocardial hypoxemia damage might have been involved. the patient required inotrope/vasoactive support for several days and eventually recovered fully with normal heart function. our observations confirm the responsiveness of this infection to antiviral therapy. we adopted a two-modality administration, both oral and inhaled. our choice was made in consideration of the decrease in gut motility and adsorption usually observed in critically ill patients. the world health organization (who) has questioned the sensibility of rt-pcr analysis for h n in pharyngeal swab sample, encouraging analysis on samples from the lower respiratory tract. we routinely monitor h n infection on three compartments: pharyngeal swab, subglottic aspiration, and bronchoalveolar lavage. in our experience, bronchoalveolar lavage at admission was positive in all patients while pharyngeal swab resulted positive in only % of cases. as shown in figure , rt-pcr from pharyngeal swab at icu admission failed to demonstrate the viral infection in patients. similarly, the time course showed that rt-pcr from pharyngeal swab resulted negative in an average time of days after therapy start. conversely rt-pcrs from bronchoalveolar lavage remained positive for a longer period and resulted more reliable for infection monitoring and assessment of the efficacy of administered therapy. based on our experience, rt-pcr from bronchoalveolar lavage resulted to be the most reliable method to diagnose and monitor h n infection, since pharyngeal swab does not offer enough sensibility, neither for antiviral therapy initiation nor for antiviral therapy management. as subglottic aspiration resulted persistently negative, we do not recommend this sampling for diagnosis and monitoring of h n infection. despite the severe clinical pictures, we experienced a very low mortality rate: only one patient out of died ( , %). one of the surviving patients presented a lung cavern for a past pulmonary infection, and deceased for a secondary superinfection by aspergillus, probably already colonizing lung parenchyma before the onset of viral infection. our mortality rate is surprisingly low in comparison to a larger series of h n patients, even when extracorporeal support technique were employed [ , ] . our finding can be related to the small number of patients included the study and definitive comparison with larger studies could be misleading. however, despite the severity of symptoms and the rapid progression to ards, h n respiratory failure presents a relatively benign course when adequately treated, if compared to non-h n induced ards, reported to have a mortality rate from % to % [ ] [ ] [ ] [ ] . several factors may account for the favourable outcome in our series. all patients received protective ventilation. in particular, ecmo support permitted the maintenance of patients under a protective tidal volume with a respiratory rate below per min, and a fio below %, compared with non-ecmo patients who needed a higher respiratory rate and fio to maintain an acceptable pulmonary gas exchange. the availability of easily accessible tools for pulmonary mechanics evaluations on modern ventilators allowed an individualized and appropriate setting of ventilation pressure within the thresholds of so called "protective ventilation" [ ] . furthermore, early access to ecmo resource allowed the maintenance of protective ventilation even in more severe patients (table ). in this regard, lactate dehydrogenase is commonly considered a marker of lung damage, and in h n pneumonia is reported as high [ ] . in our ecmo patients, lactate dehydrogenase values presented lower levels than in non-ecmo patients ( u/l vs iu/l, respectively), suggesting that in ecmo patients the reduced need of pulmonary ventilation could reduce lung ventilatory stress and enhance healing, regardless of the more impaired lung condition. however, it is possible that, since the technique has gained popularity and experience gathered to demonstrate its feasibility, we used ecmo also in patients who might previously have been successfully treated conventionally, and this may have influenced mortality. moreover, more than half of our ecmo patients needed to be land-transported from other hospitals in an advanced stage of respiratory failure. this may have further encouraged an early treatment with ecmo to ensure the safest transport. bleeding is commonly reported during ecmo treatment [ ] , and either anticoagulation or platelet and coagulation cascade activation through oxygenator and pump is involved [ ] . in our population bleeding also occurred more frequently in ecmo patients, and they required more transfusions compared to non ecmo patients. nevertheless, in our experience, bleeding from cannulas insertion site or from upper airways, despite requiring transfusion, were not life threatening, and could be managed. in only two cases did severe bleeding occur in the lower respiratory tract. fortunately in one case it occurred during weaning from ecmo, and it ceased after extracorporeal support removal. the other patient died from pulmonary aspergillosis and the haemorrhage could be also related to parenchyma disruption caused by the fungus. monitoring heparin regimen is extremely important during extracorporeal circulation, and activated clotted time is commonly measured bedside. some debate exists regarding the optimal range and the accuracy of pointof-care measuring devices [ ] [ ] [ ] . in our protocol, we usually measured aptt every two hours with hemochron jr. in order to closely monitor heparin administration in the low range of dosage. in our clinical practice, lung recovery and response to treatment are daily assessed by lus examination, following several recent reports which underline the reliability of lus in the evaluation and management of chest disorders [ , ] . despite ct-scan is the reference technique for evaluating lung lesions, it requires a transitory disconnection of the patient from the ventilator to permit the transportation radiology suite with potential risk of alveolar de-recruitment and worsening of oxygenation. moreover, severe complications have been reported in intra-hospital transportation of critically ill patients [ , ] . as we recently reported [ ] , the routine use of bedside lus has significantly reduce of the number of ct-scan and chest x-ray examinations in critical patients. the potential clinical benefit of reducing in-hospital transport for diagnostic radiology, it can be particularly relevant in patients with ecmo. in these patients, in fact, transportation requires time and a significant commitment of resources, although it was proved feasible both for inhospital [ , ] and for inter-hospital long distance transportations [ , ] . another advantage of lus is the ability to evaluate the effectiveness of alveolar recruitment manoeuvres with the possibility to visualize real-time imagines of lung parenchyma re-aeration [ , , ] . finally, pleural effusions can be accurately diagnosed and monitored with lus and in case of need for treatment an ultra-sound guided technique is recommended [ , ] . this option seems to be particularly appropriate ecmo patients, where bleeding for conventional chest tube placement can occur in consideration of the need of heparin infusion. the present case series comprises a small number of patients, and naturally, it cannot be considered a high grade of evidence trial. however, our experience might be helpful for intensivists challenging h n -induced ards. for h n infection monitoring (or diagnosis, if patient was intubated before) bronchoalveolar lavage can be more reliable than pharyngeal swab in order of the higher sensitivity. in our clinical practice, ecmo therapy resulted safe and feasible in the context of a life threatening condition, and it might be taken into consideration as a therapeutic choice rather than a rescue solution in experienced centers. • ecmo might be taken into consideration as a safe therapeutic choice rather than a rescue solution in ards. • rt-pcr from bronchial lavage is more accurate than from pharyngeal swab, in h n diagnosis. • lung ultrasonography is a safe and reliable method to follow the pathology evolution/recovery of lung. • lung ultrasonography can limit the need of ct-scan and chest x-ray examinations. list of abbreviations ards: acute respiratory distress syndrome; bmi: body mass index; cvvh: continuous veno-venous hemofiltration; ecmo: extracorporeal membrane oxygenation; icu: intensive care unit; los: length of stay; lus: lung ultrasound; rt-pcr: real-time reverse transcriptase-polymerase-chain-reaction; saps: simplified acute physiology score. pneumonia and respiratory failure from swine-origin influenza a (h n ) in mexico intensive care adult patients with severe respiratory failure caused by influenza a (h n )v in spain hospitalized patients with h n influenza in the united states severe respiratory disease concurrent with the circulation of h n influenza acute respiratory distress syndrome higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome cdc protocol of realtime rt-pcr for influenza a (h n ). geneva: world health organization the value of lung ultrasound monitoring in h n acute respiratory distress syndrome ultrasound diagnosis of alveolar consolidation in the critically ill lung ultrasound in acute respiratory distress syndrome and acute lung injury the coming boom ultrasound estimation of volume of pleural fluid in mechanically ventilated patients the use of point-of-care bedside lung ultrasound significantly reduces the number of radiographs and computed tomography scans in critically ill patients time needed to achieve completeness and accuracy in bedside lung ultrasound reporting in intensive care unit h n influenza in australia and new zealand influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review myocarditis in a juvenile patient with influenza a virus infection extracorporeal lung support for patients who had severe respiratory failure secondary to influenza a (h n ) infection in canada efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial mortality rates for patients with acute lung injury/ ards have decreased over time has mortality from acute respiratory distress syndrome decreased over time?: a systematic review extracorporeal life support for management of refractory cardiac or respiratory failure: initial experience in a tertiary centre ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. the acute respiratory distress syndrome network extracorporeal membrane oxygenation in adults with severe respiratory failure: a multicenter database coagulation and anticoagulation in extracorporeal membrane oxygenation long-term extracorporeal circulation management: the role of low-and high-range heparin act tests maintaining adequate anticoagulation on extracorporeal membrane oxygenation therapy: hemochron junior low range versus hemochron activated clotting time systems vary in precision and bias and are not interchangeable when following heparin management protocols during cardiopulmonary bypass ultrasound assessment of antibiotic-induced pulmonary reaeration in ventilator-associated pneumonia* intrahospital transport of critically ill patients review of a large clinical series: intrahospital transport of critically ill patients: outcomes, timing, and patterns chest and abdominal ct during extracorporeal membrane oxygenation: clinical benefits in diagnosis and treatment management benefits and safety of computed tomography in patients undergoing extracorporeal membrane oxygenation therapy: experience of a single centre inter-hospital transportation of patients with severe acute respiratory failure on extracorporeal membrane oxygenation-national and international experience transportation of critically ill patients on extracorporeal membrane oxygenation safety of ultrasound-guided thoracentesis in patients receiving mechanical ventilation the study was supported by institutional funds only. authors' contributions ap, mb, gc, ap, sb, mc, gs, mb, vg, gg organized the ecmo center. ap, mb, gc, gs, vg, gg designed the study. ap, mb, gc, ap, mc, sb, mb, sb reviewed the literature. sb collected data. pb and cl performed cardiologic and transesophageal assistance. mb performed ecmo invasive procedures. aa and ra performed laboratory and microbiological analysis; gc, gz, sb, cl wrote the draft. all authors have read, revised and approved the manuscript. the authors declare that they have no competing interests. key: cord- - ki dzwb authors: patel, sunil; shah, neeraj m.; malhotra, akanksha m.; lockie, christopher; camporota, luigi; barrett, nicholas; kent, brian d.; jackson, david j. title: inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation date: - - journal: erj open res doi: . / . - sha: doc_id: cord_uid: ki dzwb patients with near-fatal asthma requiring ecmo are more likely to be younger and female and are also likely to have positive viral and fungal isolates on bronchoalveolar lavage when compared to those receiving conventional mechanical ventilation http://bit.ly/ s sac incidence of positive bacterial isolates. compared to the mechanical ventilation group, days on mechanical ventilation were significantly greater in the ecmo cohort ( ± versus ± days, p= . ). in addition, length of stay (los) in the icu ( ± versus ± days, p= . ) and in hospital ( ± versus ± days, p< . ) were significantly longer in the ecmo group. higher crp levels on admission to hospital were associated with a more prolonged hospital and icu stay in the mechanical ventilation group only ( p< . ). all ecmo patients survived to hospital discharge; however, two mechanically ventilated patients died during their icu admission. in this retrospective review of adult asthmatics admitted to intensive care for a near-fatal acute exacerbation, we report that the requirement for ecmo was associated with younger age, female sex and the presence of either fungal or rhinoviral infection in the lower airway. in addition, a higher white cell count, a more profound degree of hypercapnia and acidaemia, as well as an increased los in the icu and hospital overall, were observed in those requiring ecmo support. these findings may suggest the possibility of complex inflammatory cascades that lead to lung injury, refractory hypercapnic respiratory failure and failure of mechanical ventilation. from review of the clinical notes, ecmo was indicated in all cases due to maximal mechanical ventilatory support being reached or deemed extremely detrimental to the individual (i.e. leading to ventilator-induced lung injury) rather than overwhelming infection. despite this finding, all patients received empirical antibacterial and/or targeted anti-influenza treatment (if confirmed as positive or deemed high risk) on admission to hospital before antimicrobial regimes were rationalised based on positive isolates, a practice that is common when respiratory/ventilatory failure is unexplained or deteriorating. single-site positive isolates of candida species were not treated. there were no cases of fungaemia and antifungal therapy was only started in the presence of raised peripheral blood markers (i.e. β-d-glucan) or high index of suspicion of fungal infection. all patients with bal isolates of aspergillus species were treated. in addition, we did not collect data relating to prehospital use of antimicrobial therapy. studies have shown that virally mediated inflammatory pathways (acute or quiescent) are implicated in near-fatal asthma and occur in as much as % of patients [ ] . the association of fungal isolates with near-fatal asthma is a novel finding but consistent with the association of these organisms in acute asthma [ , ] . this finding suggests the possibility of defective antifungal and/or antiviral immune pathways in these patients. rhinovirus is well recognised as a trigger for acute asthma, and deficient antiviral type and interferons has been reported in asthma [ ] [ ] [ ] . a limitation of this study is its retrospective design, which introduces the possibility of information bias. additionally, some important clinical background characteristics, including prior exacerbation frequency and information regarding adherence to maintenance inhaled therapies, were not available. however, we were able to partially acquire data relating to prehospital corticosteroid use (table ) . from these data, we found that a greater percentage of patients without any formal treatment for their asthma required ecmo ( % versus %). interestingly, a lower percentage of patients receiving moderate and high-dose inhaled corticosteroids (ics) and/or long-acting β-agonists required ecmo compared to those requiring mechanical ventilation only (moderate: % versus %; high: % versus %). furthermore, no patient in either treatment group required long-term oral corticosteroids or biologic agents. in those requiring ecmo, we found that in the year preceding acute admission, only % (seven out of ) received regular ics, % had documentation of regular short-acting β-agonist use and % had received at least one -day course of oral corticosteroids (data not shown). similar data in the mechanical ventilation-only group were not collected and therefore, in this cohort, we cannot comment on whether levels of treatment are associated with need for ecmo. of note, no patient had an indication other than asthma for corticosteroid use or other immunosuppression of any form; thus, the microbiological isolates are unlikely to have been influenced by secondary factors. to date, this is the first case series investigating inflammatory and microbial factors associated with the need for ecmo in near-fatal asthma and highlights rhinovirus infection as well as positive fungal isolates as being particularly associated with the need for ecmo. it is noteworthy that despite the severity of illness and inability to mechanically ventilate these patients, ecmo was associated with % survival and widespread access to this life-saving therapy should be made a priority. extracorporeal membrane oxygenation in severe acute respiratory failure. a randomized prospective study mechanically ventilating the severe asthmatic epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma fungal sensitization is associated with increased risk of life-threatening asthma viral infections in allergy and immunology: how allergic inflammation influences viral infections and illness il- -dependent type inflammation during rhinovirus-induced asthma exacerbations in vivo the role of viruses in acute exacerbations of asthma key: cord- -furt xcn authors: hraiech, sami; bonnardel, eline; guervilly, christophe; fabre, cyprien; loundou, anderson; forel, jean-marie; adda, mélanie; parzy, gabriel; cavaille, guilhem; coiffard, benjamin; roch, antoine; papazian, laurent title: herpes simplex virus and cytomegalovirus reactivation among severe ards patients under veno-venous ecmo date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: furt xcn background: herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ards). however, little is known about herpes simplex virus (hsv) and cytomegalovirus (cmv) reactivation occurring in patients with severe ards under veno-venous extracorporeal membrane oxygenation (ecmo). we tried to determine the frequency of herpesviridae reactivation and its impact on patients’ prognosis during ecmo for severe ards. results: during a -year period, non-immunocompromised patients with a severe ards requiring a veno-venous ecmo were included. sixty-seven patients ( %) experienced hsv and/or cmv reactivation during ecmo course ( viral co-infection, hsv alone, and cmv alone). hsv reactivation occurred earlier than cmv after the beginning of mv [( – ) vs. ( – ) days; p < . ] and after ecmo implementation [( – ) vs. ( – ) days; p < . ]. in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation [( – . ) vs. . ( – ) days; p < . ], a longer duration of ecmo [ ( – . ) vs. ( – ) days; p < . ], and a prolonged icu [ ( . – . ) vs. ( – ) days; p < . ] and hospital stay [ ( – . ) vs. ( – ) days; p < . ] as compared to non-reactivated patients. however, in multivariate analysis, viral reactivation remained associated with prolonged mv only. when considered separately, both hsv and cmv reactivation were associated with a longer duration of mv as compared to non-reactivation patients [ ( . – ) and ( . – ), respectively, vs. . ( – ) days; p < . ]. co-reactivation patients had a longer duration of mv [ . ( – . ); p < . ] and icu stay [ . ( . – ) vs. . ( . – . ) and ( – . ), respectively] as compared to patients with hsv or cmv reactivation alone. in multivariate analysis, hsv reactivation remained independently associated with a longer duration of mv and hospital length of stay. conclusions: herpesviridae reactivation is frequent among patients with severe ards under veno-venous ecmo and is associated with a longer duration of mechanical ventilation. the direct causative link between hsv and cmv reactivation and respiratory function worsening under ecmo remains to be confirmed. herpes simplex virus (hsv) and cytomegalovirus (cmv) belong to the herpesviridae family and are characterized by an often asymptomatic primo-infection generally during childhood followed by a latency phase. in immunocompromised subjects, herpesviridae are common viral causes of opportunistic infections. but hsv and cmv reactivations are also frequently reported in intensive care unit (icu) non-immunocompromised patients [ , ] . reactivation ranges from to % and to % for hsv and cmv, respectively [ , ] . herpesviridae reactivation in immunocompetent icu patients is associated with poorer outcome [ ] . hsv pulmonary reactivation has been described to be associated with a longer mechanical ventilation (mv) duration, icu stay and mortality [ , , ] . cmv reactivation is also associated with a higher mortality, mv duration and icu length of stay [ ] . in particular, cmv has been identified as a cause of persistent acute respiratory distress syndrome (ards) [ ] and has also been shown to increase the mortality in ards patients [ ] . however, despite these associations, the debate on the proper pathogen role of herpesviridae rather than being a witness of patients' severity is still ongoing. studies failed to demonstrate that cmv prophylaxis was able to decrease il- plasma levels in cmv seropositive critically ill patients [ ] or to decrease mortality [ ] . the role of herpesviridae pre-emptive treatment among icu patients has been recently evaluated in a randomized controlled trial (rct) (nct ). the data concerning hsv showed that preemptive acyclovir did not decrease the duration of mv although a trend towards lower mortality was found in treated patients [ ] . the most frequent risk factors for cmv and hsv reactivation in the icu are patients severity, sepsis, prolonged mv [ ] , high-dose corticosteroid therapy, acute renal failure or massive transfusion [ ] , with a strong association for mv and sepsis [ ] . patients under veno-venous extracorporeal membrane oxygenation (vv ecmo) for severe ards [ ] often combine several or all of these risk factors [ ] . despite the uncertainties regarding the exact role of herpesviridae reactivation in immunocompetent critically ill patients, it might add to the pulmonary pathology in patients with ards. in experimental studies, cmv reactivation led to increased pulmonary fibrosis [ ] and accessing bacterial pneumonia [ ] . these findings suggest that herpesviridae-related pulmonary pathology may be causally linked to the clinical disease course following ards onset, especially in the most severely ill patients who require prolonged mechanical ventilation, and might particularly concern patients under ecmo. however, despite the tight link that seems to exist between herpesviridae, mechanical ventilation and ards, no study has investigated the occurrence of hsv and/or cmv reactivation in patients under vv ecmo. in this study, we aimed to assess the frequency of herpesviruses reactivation during ecmo course and to determine its impact on patients' prognosis. we conducted an observational, retrospective study in a medical icu (ards and ecmo referee center) at the marseille university hospital between december and april . patients aged or more, hospitalized in the icu for severe ards requiring a vv ecmo for days or more were included. hsv and/or cmv reactivation (see definition below) occurring after ecmo insertion was screened for these patients. patients with immunosuppression (immunosuppressive treatments including corticosteroids > . mg/kg/day prednisoneequivalent within days prior to inclusion, severe neutropenia < . g/l of neutrophils, hiv seropositivity, bone marrow or solid organ transplantation), antiviral therapy against hsv and/or cmv prior to inclusion, or hsv/cmv reactivation known at the time of ecmo insertion were excluded. at the time of the study, hsv and cmv screening were routinely performed twice weekly in all patients under mv. hsv reactivation was defined by a positive qualitative throat sample (virocult ® ) pcr. cmv reactivation was defined by a positive quantitative blood pcr with a copy number > /ml. when a broncho-alveolar lavage (bal) was performed for suspicion of ventilator-associated pneumonia, hsv and cmv pcr were systematically realized in bal and blood. cmv viral loads were converted in iu/ml and qualified as "high reactivation" for viral loads greater than or equal to iu/ml or "low reactivation" for viral loads of - iu/ml [ ] . cmv antigenemia was also researched in case of reactivation suspicion. the following data were retrospectively recorded from the patients' medical file: age, sex, simplified acute physiologic score ii (saps ii) [ ] , sequential organ failure assessment (sofa) score [ ] , presence of co-morbidities, presence of previous immunosuppression, cause of ards, date of mv initiation, date of ecmo implementation, other organ failure associated with ards during icu stay (in particular need for catecholamines or renal replacement therapy), blood transfusion, post-aggressive pulmonary fibrosis (defined by an alveolar procollagen iii higher than µg/l) [ ] , time of hsv/cmv reactivation, delay between mv and hsv/cmv reactivation, delay between ecmo and hsv/cmv reactivation, duration of mv (from the day of intubation to the day of mv weaning), ecmo duration (from the day of ecmo implementation to its removal or death), ecmo-free days at day , ventilator-free days (vfd) at day , icu length of stay [from the day of icu admission (in the first icu if the patient was referred from another hospital) to discharge], hospital length of stay [from the admission to hospital (in the original hospital if the patient was referred from another hospital) to discharge to home or to rehabilitation ward], icu and hospital mortality, acyclovir or ganciclovir treatment after reactivation under ecmo. statistical analysis was performed using ibm spss statistics version . (ibm spss inc., chicago, il, usa). first, a univariate analysis was performed. data were expressed as mean ± the standard deviation or median with interquartile range for the quantitative variables, and as numbers and percentages for the categorical variables. patient characteristics and clinical outcomes were compared to the viral reactivation status of the patients or antiviral treatment. groups were compared using the chi-square or fisher's exact test for categorical characteristics, and using the student's t test or mann-whitney u test for continuous ones, as appropriate. then a multivariate analysis was performed to assess the independent effect of viral reactivation on different outcomes. multiple linear regression was used to construct models. variables that were marginally significant (p < . ) in the univariate analysis, and that had clinical relevance were included in the regression models. beta coefficients and their p values were presented. a two-sided p value less than . was considered statistically significant. during the study period, patients were admitted to our icu for severe ards requiring a vv ecmo for days or more (see flowchart, fig. ). of these, patients were excluded because of immunosuppression ( patients), hsv/cmv reactivation at the time of ecmo implementation ( patients) or acyclovir/ganciclovir treatment before ecmo ( patients). among the patients included, patients ( %) experienced hsv and/or cmv reactivation during the icu stay and ( %) were free from hsv/cmv reactivation at the time of icu discharge or death. population's characteristics are presented in table . patients with hsv/cmv reactivation had a longer mv before ecmo than non-reactivated patients (p < . ). mean cmv viral loads (in blood or bal) were ± iu/ml with a high reactivation for ( %) patients. clinical outcomes are presented in table . patients exhibiting hsv/cmv reactivation received more transfusion [ ( - . ) vs. ( - ) red cells pellets; p = . ]. pulmonary fibrosis, diagnosed by an alveolar procollagen iii > µg/l, was not different between both groups. in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation [ ( - when separating patients according to hsv, cmv, and co-reactivation (hsv and cmv), we found that hsv reactivation was associated with a longer duration of in multivariate analysis (table ) , only hsv reactivation remained independently associated with a longer duration of mv and hospital length of stay but a shorter icu stay. thirty-four patients ( %) received an antiviral treatment (acyclovir or ganciclovir) during ecmo course. no difference in clinical outcomes was found between treated and untreated patients except a trend towards longer duration of mv for treated patients (additional file : table s ). multivariate analysis evaluating, after adjustment on patients' severity and length of mv and ecmo duration before reactivation, the clinical impact of hsv/ cmv reactivation. the coefficient designates the number of days by which the different endpoints are affected data are presented as median and interquartile range or absolute value and percentage a p < . compared with non-reactivation group until today, no data have been published concerning herpesviridae reactivation in icu patients under vv ecmo for severe ards. in this retrospective study covering a -year period, we found that hsv/ cmv reactivation was frequent and concerned more than half non-immunocompromised patients, which is higher than that described in previous studies including all icu patients [ , , ] . this might be explained by several reasons: the use of pcr to diagnose reactivation with a higher sensitivity than older technics, the age of our cohort of patients (with a high probability of seropositivity for hsv and cmv at icu admission) and the frequency of sepsis with a probable induced "immunoparalysis" [ ] . in our cohort, hsv reactivation occurred earlier than cmv reactivation and the median time of reactivation for both viruses was comparable to what is described in "non-ecmo" patients [ ] . cmv viral loads in blood and bal were high in almost all patients. elevated cmv viremia is associated with a higher risk of death or prolonged hospitalization [ ] . patients included were comparable except for the duration of mv before ecmo that was longer in the reactivation group. it is well known that mv is a risk factor for herpesviridae reactivation with a strong association for cmv [ ] . we found that herpesviridae reactivation was associated with a prolonged mv, this association persisting in multi-variate analysis. we also found in these patients a prolonged ecmo duration, icu, and hospital stay, although not confirmed in multivariate analysis. in a recently published meta-analysis, li et al. [ ] showed that cmv reactivation was associated with an increase of days in mv and a days increase in icu stay. these results confirmed those published by limaye et al. [ ] , which showed that cmv viremia among icu patients was associated with a higher risk of death or prolonged icu stay > days. similarly, in a case-control study [ ] , cmv reactivation was associated with a prolonged duration of mv and icu stay. in a specific population of ards patients, ong et al. [ ] demonstrated that patients with cmv reactivation had a ( - ) days median duration of mv as compared to ( - ) days for non-reactivated patients. icu length of stay was also longer [ ( - ) vs. ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days] for reactivated patients. same results have been published concerning hsv reactivation [ , ] , especially during ards. our findings suggest that herpesviridae reactivation is associated with worse outcomes for ards patients including when they are under ecmo. when examining the impact of each virus separately, we found that both hsv and cmv were associated with a prolonged mv, and also ecmo duration for hsv. coreactivation had a negative effect not only on mv and ecmo duration but also on icu and hospital stay, as compared to patients free from reactivation or with only one virus. hsv was independently associated with a longer duration of mv and hospital length of stay but, surprisingly, a shorter icu stay. these results highlight the potential negative role of hsv in ards patients under ecmo. very recently, luyt et al. [ ] showed that preemptive treatment with acyclovir, compared to placebo, for mechanically ventilated patients with oropharyngeal hsv reactivation, was not associated with shorter mv duration. however, a trend towards lower day- mortality was observed in the acyclovir group. in our cohort, more than half of the patients were treated after the diagnosis of viral reactivation. treatment with acyclovir or ganciclovir did not improve the outcomes, with a trend for longer duration of mv in the sub-group of treated patients. these results might be explained by the fact that anti-viral treatment was decided by clinicians more frequently in case of worsening respiratory status, persisting fever or end-organ hsv/cmv disease, and so reserved for the most severe patients. we did not find any increase in renal failure in patients receiving antiviral drugs, which was also noticed in luyt et al. 's study [ ] . however, we cannot exclude any other side effects. our study has some limitations. first, the retrospective design of our cohort, counterbalanced by the important number of patients included during this -year period. second, the applicability of our results to the general population of patients under ecmo must be considered cautiously considering the high rate of patients treated with antiviral drugs after reactivation. however, in non-emco patients, routine screening of herpesviridae has been reported as well as the use of antiviral treatment despite the lack of recommendation [ , , ] . third, few patients developed an isolated cmv reactivation. this precludes to conclude clearly on the specific impact of cmv in our cohort of patients. fourth, our methods do not prevent competing risks. in particular, the difference in mv duration between reactivated and non-reactivated patients might have been influenced by the high mortality reported. however, this mortality was similar in both groups and the difference of mv duration persisted when considering only the patients discharged alive from the icu. finally, despite the statistical association, it is not possible to conclude whether herpesviridae reactivation is directly responsible for worse clinical outcomes or if it is a consequence and a witness of the severity of the disease, as in non-ecmo populations [ ] . herpesviridae reactivation is frequent among patients with severe ards under veno-venous ecmo and is associated with a prolonged mechanical ventilation. this association is present for hsv as well as cmv and also for co-reactivation. the direct causative link between hsv and cmv reactivation and respiratory function worsening under ecmo remains to be confirmed. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file : table s . clinical outcomes according to anti-viral treatment. abbreviations ards: acute respiratory distress syndrome; bal: broncho-alveolar lavage; cmv: cytomegalovirus; ecmo: extracorporeal membrane oxygenation; hiv: human immunodeficiency virus; hsv: herpes simplex virus; icu: intensive care unit; il- : interleukine ; iu/ml: international units/milliliter; mv: mechanical ventilation; pcr: polymerase chain reaction; saps ii: simplified acute physiologic score ii; sofa: sequential organ failure assessment; vfd: ventilator free days; vs.: versus; vv: veno-venous. active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation cytomegalovirus reactivation in icu patients cytomegalovirus reactivation in critically-ill immunocompetent patients cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients is acyclovir effective among critically ill patients with herpes simplex in the respiratory tract? cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis a contributive result of open-lung biopsy improves survival in acute respiratory distress syndrome patients cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome effect of ganciclovir on il- levels among cytomegalovirus-seropositive adults with critical illness: a randomized clinical trial safety and efficacy of antiviral therapy for prevention of cytomegalovirus reactivation in immunocompetent critically ill patients: a randomized clinical trial acyclovir for mechanically ventilated patients with herpes simplex virus oropharyngeal reactivation: a randomized clinical trial prevalence and mortality associated with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit cytomegalovirus infection in critically ill patients: associated factors and consequences cytomegalovirus infection in immunocompetent critically ill adults: literature review formal guidelines: management of acute respiratory distress syndrome long-term neurocognitive outcome is not worsened by of the use of venovenous ecmo in severe ards patients pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice cytomegalovirus reactivation enhances the virulence of staphylococcus aureus pneumonia in a mouse model a new simplified acute physiology score (saps ii) based on a european/north american multicenter study the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine type iii procollagen is a reliable marker of ards-associated lung fibroproliferation early herpes and ttv dnaemia in septic shock patients: a pilot study cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we acknowledge mrs claudine marion and sabine depetris for their help.authors' contributions sh, eb, cg, ma, gp, gc and bc collected and analyzed the data. sh, eb, cg, ar and lp analyzed and interpreted more precisely the data. cf, al, sh and cg performed the statistical analysis. sh, eb and lp wrote the manuscript. all authors read and approved the final manuscript. the authors received no funding for this work. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. patients and their relatives were informed of the possibility of the use of medical data for retrospective studies and did not manifest opposition. the study was approved by the "portail d'accès aux données de santé de l' assistance publique des hopitaux de marseille" ("règlement général pour la protection des données" registration number - ). not applicable. the authors declare that they have no competing interests. key: cord- - sscf lq authors: shi, jingyi; wang, chunxia; cui, yun; zhang, yucai title: extracorporeal membrane oxygenation with prone position ventilation successfully rescues infantile pertussis: a case report and literature review date: - - journal: bmc pediatr doi: . /s - - - sha: doc_id: cord_uid: sscf lq background: bordetella pertussis can cause fatal illness with severe acute respiratory distress syndrome (ards) and pulmonary hypertension (pht). case presentation: a -month-old non-vaccinated boy with b. pertussis infection who developed ards was treated by extracorporeal membrane oxygenation (ecmo). during his ecmo support stage, sudden occurred decreasing of ecmo flow implied increasing intrathoracic pressure. the airway spasm followed caused sudden drop of ventilator tidal volume as well as poor lung compliance. prone position ventilation and bundle care were conducted as lung protection ventilator strategy. after -h of ecmo support, the patient was weaned off ecmo, and extubated one week later. conclusions: in this patient with severe ards caused by bordetella pertussis, ecmo was performed for cardiopulmonary support and rescued the infant with severe pertussis. during ecmo support period, prone position ventilation and care bundle nursing strategy contributed to the relief of continuous airway spasm. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. pertussis, caused by bordetella pertussis infection, is the fifth leading cause of vaccine preventable deaths in children under years of age and remains a public health concern worldwide [ ] . for the infant with pertussis, the prognosis is worse if the child develops pneumonia, worsening respiratory failure, pht and requires mechanical ventilation [ ] . for the critical care management of the infant with pertussis, strategies include conventional ventilation, high-frequency oscillatory ventilation, plasmapheresis, inhaled nitric oxygen, leukodepletion, and more recently, extracorporeal membrane oxygenation (ecmo) [ , ] . prior reports from the extracorporeal life support organization (elso) registry demonstrated survival rates of % for pertussis patients receiving ecmo support [ , ] , which is rather lower than other ecmo respiratory indications. recent report based on data from elso registry and expanded dataset from individual institutions demonstrated that younger age, vasoactive use, pht and a rapidly progressive course were independently and significantly associated with higher mortality [ ] . the patient with pertussis is characterized by increased mass of leukocytes and high level of pertussis toxin. pertussis toxin can cause the occlusion of the pulmonary vessels by the increased mass of leukocytes, which leads to pht, and even includes acute pulmonary vasoconstriction. the refractory airway spasm is the most common clinical manifestation. until now, there has no report about the effect of recurrent pertussis toxins-induced airway spasm on the management of ecmo in infantile fetal pertussis. we report the successful outcome of a -month-old infant diagnosed as severe pertussis treated by early initiation of ecmo. both prone position ventilation and care bundle might be considered as key factors of the lifesaving support under ecmo in infant with severe pertussis complicated with recurrent airway spasm. a -month old, . kg, male baby born at weeks of gestation was admitted to a local hospital with a -day history of cough, wheezing, -day history of fever and with pleural effusion indicated by chest x-ray. detection of bordetella pertussis by polymerase chain reaction was positive with the nasopharyngeal specimen. the child was admitted to pediatric intensive care unit (picu) in shanghai children's hospital with breathless with a temperature of . °c and heart rate to beats/ min, who developed respiratory failure requiring intubated and mechanical ventilation [positive end-expiratory pressure (peep) of cmh o; a pressure support of cmh o; a respiratory rate (rr) of /min; and a fraction of inspired oxygen of . ; peak inspiratory pressures (pips) were between and cmh o]. meanwhile, laboratory studies revealed the presence of leukocytosis [ , white blood cells (wbcs)/μl] with mg/l c-reactive protein (crp). a chest x-radiograph showed dense opacification of the right upper and right middle lobe and patchy opacification of the left upper lobe (fig. a) . over the next h, despite application of lung protective strategies and a restrictive fluid strategy, the patient deteriorated with worsening lung compliance and hypoxemia, as well as the dense opacification of the right upper and right middle lobe enlarged (fig. b) . at the same time, the tidal volume decreased from ml/kg to . ml/kg, and cdyn (pulmonary dynamic compliance) decreased from . ( . /kg) to . ( . /kg). the patient's pips continued to rise to cmh o with a plateau pressure of cmh o, pao /fio dropped to mmhg and oxygen index (oi) raised to lasting for h. importantly, the echocardiography (performed rd day after admission) demonstrated pht ( mmhg) with a normal left ventricular function. the diameter of the pulmonary artery was cm, pulmonary artery blood flow was . m/s, the tricuspid regurgitation flow was . m/s, the tricuspid annulus was . cm, and tapse was . furthermore, septic shock occurred, norepinephrine ( . μg/kg.min) and dobutamine ( μg/kg.min) were needed to maintain his blood pressure. considering in anticipation of a rapid hemodynamic collapse resulting from severe pht in pertussis, the initiation of ecmo was performed with an arterial blood gas noted as ph . , paco . mmhg and pao mmhg. the ecmo support was equipped with a centrifugal pump and an artificial lung was used (medtronic bio-medicus, minneapolis, mn, usa). the patient inserted cannula through right neck vessels, and was placed on veno-arterial (va) ecmo support with a during the first days of ecmo support, the tidal volume of this patient was only . ml/kg, and lung compliance was poor. prone position ventilation was conducted. a team requires staff members participated. a doctor positioned up to the patient's head and fixed the catheters, one nurse positioned on each side of the bed to manage the lines and tubes. we firstly placed a blanket around the patient's arms and turned the patient toward the ventilator. then, the doctor held the patient's head and fixed the catheters, while two nurses turned the patient prone. lastly, we straightened the blanket and adjusted lines and tubes, and placed the patient's arms in the swimmers position (the arms were positioned up toward the baby's shoulders). during this process, another doctor was responsible for monitoring the ecmo and a third nurse was responsible for administering drugs. to supine the patient, the process was performed reversely. there was no change in cannula position shown by x-ray when changing position (fig. a, b) , and there was no malfunction of blood access due to bending or dislodgement of the cannula when changing position. at day after ecmo initiation, exhaled tidal volumes were increased to ml/kg and effusion in lung were improved indicated by chest radiographs (figs. c). during the first days of ecmo support, the patient was characterized by recurrent attacks of airway spasm lasting for s to min each time. consequently, the airway spasm resulted in sudden declined ecmo flow ( . l/min), decreased blood oxygen saturation ( %), and decreased ventilator tidal volume ( ml/kg). except for prone position, magnesium sulfate was given and care bundles including hand washing, heightened focus on oral hygiene, closed endotracheal suctioning, prone position ventilation, appropriate sedation, reducing unnecessary stimulus (eg. assess the state of consciousness when put the position), following the nursing sequence of sputum aspiration, diapering and feeding, using full-barrier precautions during the insertion of all catheters were performed to help improving lung compliance and reduce airway spasm. the ecmo flow started around . l/min and was adjusted according to the hemodynamic status (maintained mean airway pressure [map] at - mmhg). the target blood flow was ml/kg/min, and coagulation profile was monitored the values of act were detected once - h and aptt were detected once per - h. according to the results of act and aptt, the dose of heparin was regulated to maintain an act of - s or aptt with . - fold of normal value. during ecmo therapy, ecmo flow was adjusted to keep the serum scvo > % and lactate level < mmol/l. the target oxygenation was a normal arterial partial pressure of carbon dioxide (paco ) and partial pressure of oxygen (pao ) (fig. ) . from the th day of ecmo therapy, the clinical feature of airway spasm was improved. and ventilator setting was gradually reduced. after -h of ecmo support, the patient was weaned off v-a ecmo. during the period of ecmo therapy, respiratory mechanical parameters were monitored as shown in fig. . and the ecmo flow dropped with the occurrence of airway spasm, the relationship between tidal volume and ecmo flow were shown in fig. , which represented the onset and impact of airway spasm, as well as the duration of prone position. the enteral nutrition (infatrini, nutricia) was conducted through nasogastric tube which provided - kcal/kg.d. one week later, the child was successfully extubated. after a -day high flow nasal cannula oxygen therapy, he was transferred to the escort ward on days after picu admission, and eventually discharged with a near normal neurologic examination. the time line of this case can be consulted in the additional file . patients infected bordetella pertussis were characterized by cough-associated apnea, cyanosis, pht and encephalopathy [ ] . when these infants with severe respiratory failure is poorly responsive to conventional and alternative therapies, ecmo can be considered as a promising rescue therapy [ ] , even if pertussis itself implies worse outcome among the indications for ecmo initiation for pediatric respiratory failure [ ] . based on elso registry data, younger age, lower pao /fio ratio, vasoactive use, pht, and a rapidly progressive course were associated with increased mortality [ ] . in this case report, the male child of -month-old was successfully recovered by v-a ecmo supporting. prone position ventilation and care bundle played crucial role in the management of ecmo flow influenced by pertussis toxin-induced airway spasm. pertussis toxin produces lymphocyte proliferation and results in a hyper viscosity, is thought to be responsible for the leukocytosis observed with pertussis infection [ ] , and results in a hyper viscosity syndrome that leads to obstruction of the pulmonary arterioles [ ] . here, we describe a -month-old boy who developed respiratory failure and septic shock induced by b. pertussis infection. the wbc count was , /μl, which was lower than the reported hyperleucocytosis (> , /μl) [ , ] . it was also reported that young infants infected with b. pertussis exhibit prolonged apneic pauses [ ] . according to the previous report [ ] , increased airway pressure decreases the transmural pressure of the right atrium and superior vena cava through lung-heart interaction. airway spasm causes airway pressure shoot up, then intrathoracic pressure increases and affect the venous return, thus decrease the preload of heart. another hypothesis is that by previous point of view b. pertussis pneumonia triggers acute pulmonary vasoconstriction resulting in the increased afterload of right heart [ ] . given that ecmo flow is affected by the preload and afterload of heart, we speculate that b. pertussis-induced bronchospasm might contribute to a sharp increase of intrathoracic pressure which reduce the venous return, as well as acute pulmonary vasoconstriction reduced ecmo flow through influencing both the preload and afterload of right heart. importantly, pertussis toxin-induced recurrent airway spasm brought the challenging for the ecmo flow management during emco support, which was the specific clinical feature in this case. during the first days of ecmo therapy, recurrent airway spasm resulted in a sudden decline in ecmo flow, decreased blood oxygen saturation, and decreased ventilator tidal volume. it is the first report about the clinical features about pertussis during emco supporting according to our knowledge. magnesium sulfate was used to relieve bronchial spasm, and had some auxiliary functions. magnesium has an effect on smooth muscle cells, with hypomagnesemia causing contraction and hypermagnesemia causing relaxation. it has been reported that intravenous magnesium sulfate benifit patients with acute severe asthma who do not respond to standard therapeutic medications [ ] . in addition, a strict following of nursing sequence of sputum aspiration, diapering and feeding, along with appropriate sedative, benefited. anti-pressure ulcer pads were put under chest and abdomen to preventing possible pressure injury while in prone position. the greatest contribution of care bundle in this patient was minimization of unnecessary stimulus thus gain the time to waiting and recovering from airway spasm. what we concerned most is that frequently sudden drop of ecmo blood flow will cause blood clotting in ecmo circulation, so we monitor both activated [ ] . in our study, the values of act and aptt were correlated well during ecmo therapy. based on our clinical experience from this case, there was no correlation between the drop of ecmo flow or the shorten of act or aptt, which need further investigation in the future. pertussis toxin-induced recurrent airway spasm resulted in decreased arterial oxygen saturation and the increased circulating leukocyte caused by pertussis toxin may restrict pulmonary blood flow, which cause cardiac failure, shock, and acute respiratory distress [ ] . prone position ventilation is an effective method for improving oxygenation in patients with acute respiratory distress syndrome (ards) [ , ] . importantly, prone positioning can be safely performed and managed among critically ill pediatric patients with ards [ ] [ ] [ ] . it has been proved that when changed from a supine to prone position, ards patients demonstrate a dramatic redistribution of ct lung densities because of re-expansion of previously atelectatic posterior regions. after perfusion improves in these previously hypoxic, vasoconstricted posterior lung regions when turn to prone position, ventilation/ perfusion improves [ ] . when the patient ventilated prone position, the central blood volume increased by shift of splanchnic blood volume to the thorax, which could induce pulmonary vascular recruitment, then airway spasm relief, thus help to prevent reductions in ecmo flow. on the other hand, prone position may facilitate sputum drainage. so we assume that prone position ventilation does not directly relief airway spasm, but it improves ventilation/ perfusion, facilitate sputum drainage, thus improves lung compliance. the effect of prone position on oxygenation-lung compliance of pediatric ards patients may be in doubt. from the research in adult ards patients, both low tidal volumes and increased proning duration contribute to a lower mortality in ards patients, and the effects were marked in the subgroup in which the duration of prone positioning was more than h/session [ ] [ ] [ ] . recent study indicated that prone positioning was performed for h, every h, for days in a -day-old infant with severe pertussis under ecmo support [ ] . thus, for pediatric ards patients, the duration and efficacy of prone position need to be verified through more clinical trials. in this case, prone ventilation proved to be effective for improving compliance indicated by significantly increased low cdyn after supine to prone and then prone to supine position. and cannula-related complications such as accidental removal or dislodgement of a central venous catheter, tracheal tube and cannula for extracorporeal circulation did not happened during prone positioning. these results suggested that prone positioning is a safe and effective procedure in patients with severe pertussis receiving extracorporeal circulation. there were some limitation in this case report. we did not continuously detect the wbc counts during ecmo support. since the patient was born premature, we are now unable to report on the long-term outcome of the patient's neurodevelopment. these need further investigation in cased with severe pertussis treated by ecmo supporting. from this case review, we speculated that ecmo management is challenging in patients with pertussis contributing to the high mortality of these patients under ecmo support. prone position ventilation contributes to better oxygenation and lung compliance. and detailed care bundle is essential for patients with pertussis challenged by recurrent airway spasm. an update of the global burden of pertussis in children younger than years: a modelling study pertussis: should we improve intensive care management or vaccination strategies? extracorporeal membrane oxygenation for pertussis: predictors of outcome including pht and leukodepletion fatal pht associated with pertussis in infants: does extracorporeal membrane oxygenation have a role? impact of rapid leukodepletion on the outcome of severe clinical pertussis in young infants burden and outcomes of severe pertussis infection in critically ill infants extracorporeal life support in pertussis development and validation of a score to predict mortality in children undergoing extracorporeal membrane oxygenation for respiratory failure: pediatric pulmonary rescue with extracorporeal membrane oxygenation prediction score bordetella pertussis infection: pathogenesis, diagnosis, management, and the role of protective immunity severe neonatal pertussis treated by leukodepletion and early extra corporeal membrane oxygenation is leukocytosis a predictor of mortality in severe pertussis infection? leukocytosis as a predictor for noninfective mortality and morbidity exchange blood transfusion in the management of severe pertussis in young infants mechanical ventilation-induced intrathoracic pressure distribution and heart-lung interactions* pathology and pathogenesis of fatal bordetella pertussis infection in infants intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy anticoagulation and coagulation management for ecmo effect of prone positioning in patients with acute respiratory distress syndrome: a meta-analysis effect of prone positioning on the survival of patients with acute respiratory failure prone position and positive end-expiratory pressure in acute respiratory distress syndrome prone positioning can be safely performed in critically ill infants and children effect of prone positioning on cannula function and impaired oxygenation during extracorporeal circulation adjunctive treatments in pediatric acute respiratory distress syndrome a comprehensive review of prone position in ards prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis prone positioning of patients in acute respiratory failure not applicable.ethical approval and consent to participate not applicable. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. authors' contributions y cui and yc zhang were the main administrators of ecmo management. jy shi and cx wang analyzed and interpreted the patient data, and are major contributors in writing the manuscript. all authors read and approved the final manuscript. our manuscript contains individual person's data in form of individual details and images. written informed consent was obtained from the parents of the patient for publication of this case report and any accompanying images. a copy of the written consent is available for review by the editor-in-chief of this journal. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -fkh fzbr authors: bednarczyk, joseph m.; kethireddy, shravan; white, christopher w.; freed, darren h.; singal, rohit k.; bell, dean; ahmed, syed zaki; kumar, anand; light, bruce title: extracorporeal membrane oxygenation for blastomycosis-related acute respiratory distress syndrome: a case series date: - - journal: can j anaesth doi: . /s - - -z sha: doc_id: cord_uid: fkh fzbr purpose: blastomyces dermatitidis is a dimorphic fungus endemic to north america capable of causing fatal respiratory failure. acute respiratory distress syndrome (ards) complicates up to % of pulmonary blastomycosis in hospitalized patients and carries a mortality of - %. this report describes the clinical course of four consecutive patients with blastomycosis-related ards treated with venovenous extracorporeal membrane oxygenation (ecmo) during - . clinical features: four adults were referred from northwestern ontario, canada with progressive respiratory illnesses. all patients developed diffuse bilateral opacities on chest radiography and required mechanical ventilation within - hr. patients satisfied berlin criteria for severe ards with trough p(a)o( )/f(i)o( ) ratios of - on positive end-expiratory pressure of - cm h( )o. wet mount microscopy from respiratory samples showed broad-based yeast consistent with b.dermatitidis. despite lung protective ventilation strategies with maximal f(i)o( ) (patients a-d), neuromuscular blockade (patients a-d), inhaled nitric oxide (patients a and d), and prone positioning (patient d), progressive hypoxemia resulted in initiation of venovenous ecmo by hours - of mechanical ventilation with subsequent de-escalation of ventilatory support. in all four cases, ecmo decannulation was performed ( - days), mechanical ventilation was withdrawn ( - days), and the patients survived to hospital discharge ( - days). conclusion: this report describes the successful application of ecmo as rescue therapy in aid of four patients with refractory blastomycosis-associated ards. in addition to early appropriate antimicrobial therapy, transfer to an institution experienced with ecmo should be considered when caring for patients from endemic areas with rapidly progressive respiratory failure. conclusion this report describes the successful application of ecmo as rescue therapy in aid of four patients with refractory blastomycosis-associated ards. in addition to early appropriate antimicrobial therapy, transfer to an institution experienced with ecmo should be considered when caring for patients from endemic areas with rapidly progressive respiratory failure. objectif blastomyces dermatitidis est un champignon dimorphique endémique en amérique du nord, susceptible de provoquer une défaillance respiratoire fatale. le syndrome de détresse respiratoire aiguë (sdra) complique jusqu'à % des cas de blastomycose pulmonaire chez les patients hospitalisés avec un taux de mortalité de % à %. ce compte rendu décrit l'évolution clinique de quatre patients consécutifs atteints de sdra lié à une blastomycose et traités par oxygénation par membrane extracorporelle (ecmo) par voie veinoveineuse entre et . cliniques quatre adultes en provenance du nord-ouest de l'ontario (canada) ont été transférés pour des maladies respiratoires évolutives. tous les patients ont développé des opacités diffuses bilatérales sur les radiographies de thorax et une ventilation mécanique a été nécessaire dans un délai de à heures. les patients répondaient aux critères de berlin pour un sdra sévère avec des rapports minimums p a o /c i o de à sur une pression positive de fin d'expiration de à cm h o. un examen microscopique sur lame humide des échantillons respiratoires a montré une levure à base large compatible avec b. dermatitidis. en dépit de stratégies ventilatoires protégeant le poumon avec une f i o maximum (patients a à d), un bloc neuromusculaire (patients a à d), du monoxyde d'azote inhalé (patients a et d), et une position en procubitus (patient d), la progression de l'hypoxémie a nécessité l'instauration d'une ecmo veinoveineuse dans un délai de à heures après l'instauration de la ventilation mécanique, suivie d'une désescalade progressive du soutien ventilatoire. dans ces quatre cas, la décanulation de l'ecmo a pu avoir lieu (entre et jours), la ventilation mécanique a été retirée (entre et jours) et les patients ont survécu après leur congé de l'hô pital ( à jours). conclusion ce compte rendu décrit la réussite de l'utilisation de l'ecmo comme traitement de secours visant à aider quatre patients atteints d'un sdra réfractaire associé à une blastomycose. en plus du traitement antimicrobien adapté, le transfert des patients vers un établissement ayant l'habitude de l'ecmo doit être envisagé au cours de la prise en charge de patients vivant en zone d'endémie et présentant une défaillance respiratoire rapidement évolutive. blastomyces dermatitidis, a dimorphic fungus endemic to well-described regions in north america, is capable of causing life-threatening disease in young immunocompetent adults. , blastomycosis remains a rare disease, but incidence reaches seven cases per , annually in northwestern ontario. although % of affected patients have primarily pulmonary involvement, clinical manifestations vary widely. [ ] [ ] [ ] up to % of hospitalized patients with pulmonary blastomycosis develop acute respiratory distress syndrome (ards). , in contrast to ards of other etiologies, patients with blastomycosis-related ards have disproportionately high reported mortality ( - %) and may be more likely to die from early refractory respiratory failure. , , expert consensus supports early aggressive treatment; however, a specific strategy has yet to be developed. venovenous extracorporeal membrane oxygenation (ecmo) has been utilized for the management of severe ards to facilitate gas exchange, allow lung rest by deescalation of ventilatory support, and provide time for resolution of the underlying disease. extracorporeal membrane oxygenation is generally considered in ards patients with refractory hypoxemia or hypercapnia despite a lung protective ventilation strategy or in those where the maintenance of adequate gas exchange requires potentially injurious applied volumes or pressures. selective application of ecmo may have resulted in a reduction in mortality among patients with severe ards secondary to h n infection. [ ] [ ] [ ] nevertheless, uncertainty exists regarding the appropriateness of ecmo during disseminated fungal infection or septic shock in adults. we describe a case series of four critically ill patients with blastomycosis-related ards treated with venovenous ecmo. ethics approval was provided by the university of manitoba health research ethics board (registration number: university of manitoba h : , june, ), and informed consent was obtained in three of four cases in which contact information was available. a retrospective cohort study was performed on all patients with blastomycosis-related ards treated with ecmo at a single canadian site during - . the ecmo referral centre is a regional tertiary care -bed academic facility that performs approximately ten venovenous ecmo cannulations for respiratory failure annually. patient demographics, ecmo-related variables, and clinical data were obtained from the medical record. descriptive statistical analysis was performed with graphpad prism v . c (graphpad software inc., la jolla, ca, usa). four adults aged - were referred from northwestern ontario, canada with progressive respiratory symptoms, including coughing, sputum production, fever, and dyspnea. three of four patients were previously healthy and immunocompetent. one patient had complex comorbidities, including hemochromatosis, type diabetes mellitus, stiff person syndrome (a rare autoimmune disorder of progressive muscle rigidity), and addison's disease. all patients required tracheal intubation and mechanical lung ventilation for hypoxemic (patient c) or mixed hypoxemic/hypercapneic (patients a, b, d) respiratory failure. on admission to the intensive care unit, the patients were hemodynamically unstable requiring vasopressor support, with apache ii scores ranging from - . the patients initially received antimicrobial therapy for community-acquired bacterial pneumonia at local emergency departments or nursing stations. upon arrival at the tertiary facility, bronchoscopy with bronchoalveolar lavage was performed. wet mount microscopy of respiratory samples showed yeast morphology consistent with b. dermatitidis, subsequently confirmed by culture. accordingly, in patients a-c, liposomal intravenous amphotericin b mgÁkg - Áday - was initiated within the first hr of hospital care. patient d was given conventional amphotericin b infusion mgÁkg - Áday - commencing at hour . three of four patients received systemic corticosteroids (methylprednisone - mg every six hours) within the first hr of mechanical ventilation. additional baseline characteristics are summarized in table . patients developed four-quadrant airspace opacification on chest radiography ( fig. ) with murray lung injury scores of . - . berlin criteria for severe ards were satisfied with trough p a o /f i o ratios of - on positive end-expiratory pressure (peep) levels of - cm h o. positive end-expiratory pressure was titrated based on observation of gas exchange during bedside peep trials. a low tidal volume ventilation strategy ( - mlÁkg - of predicted body weight) with permissive hypercapnia was used. life-threatening hypoxemia, acidosis, and injurious airway pressures developed despite % f i o (patients a-d), neuromuscular blockade (patients a-d), inhaled nitric oxide at ppm (patients a and d), and prone positioning (patient d) ( table ). in two cases, these conditions prompted dispatch of an aeromedical ecmo transport team, consisting of a cardiothoracic surgeon, perfusionist, critical care nurse, and critical care fellow, to facilitate ecmo cannulation in the peripheral hospital. in the remaining cases, the cannulation procedure was performed on-site at the ecmo facility. patients were considered for ecmo support if they had ards and satisfied one of the following three conditions: (i) a p a o /f i o ratio \ on a peep of at least cm h o, (ii) a ph \ . or p a co [ mmhg despite an optimal lung protective ventilation strategy, or (iii) plateau pressures [ cm h o despite optimal ventilatory management; and if they were within seven days of the onset of ards. if strict inclusion criteria were not met but rapid clinical deterioration was apparent, patients could be considered for aeromedical ecmo retrieval from distant sites within the centre's catchment region at the discretion of the receiving intensivist and cardiothoracic surgeon. following informed consent by the substitute decision maker, venovenous peripheral ecmo cannulation was performed at the patient's bedside under sterile conditions. one of two circuit configurations was selected at the cardiothoracic surgeon's discretion ( table ). the bifemoral configuration consisted of drainage via the left common femoral vein (lcfv) with return via a long single-stage right common femoral vein cannula directed to the atrial-caval junction. the right internal jugular configuration consisted of a single fr bicaval duallumen catheter (avalon laboratories, rancho dominguez, ca, usa) capable of drainage via the superior and inferior venae cavae and return via the right atrial inlet. in either configuration, an additional venous drainage catheter could be added at an available site to achieve adequate flows and oxygenation, if required. the circuit was connected to a biomedicus Ò centrifugal pump (medtronic, minneapolis, mn, usa) and a maquet quadrox-id oxygenator/heat exchanger (maquet cardiovascular, san jose, ca, usa). the circuits were heparin coated and primed with lactated ringer's solution ml at room temperature. the cannula position was confirmed via transthoracic or transesophageal echocardiography and chest radiography. following confirmation of adequate flow and favourable gas exchange on ecmo, inspired f i o was weaned and lung rest settings were applied to facilitate peak inspiratory pressures \ cm h o, peep - cm h o, and respiratory rate * breathsÁmin - , as described in the cesar trial. weaning from extracorporeal support was considered after a global assessment of disease resolution based on chest radiography, respiratory mechanics and work of breathing, and adequacy of gas exchange while delivering a lung protective ventilation strategy. at this point, a weaning trial of extracorporeal f i o and/or ecmo blood flow was initiated prior to release from ecmo. use of ecmo resulted in rapid improvements in oxygenation, ventilation, and acid-base status (table ) . this facilitated reductions in tidal volume and peep which resulted in significantly lower airway pressures. vasopressor requirements, hemodynamic parameters, and serum lactate levels also improved within hr of ecmo support. in three cases, continuous venovenous hemodiafiltration was incorporated into the ecmo circuit due to acute kidney injury and volume overload. this facilitated achievement of a negative fluid balance and recruitment of the native lung. a timeline of in-hospital events is presented in fig. . the duration of ecmo ranged from seven to days (table ). patients a, b, and d were relieved of mechanical ventilation at - days and were subsequently discharged with a cerebral performance category score obtained via chart review. patient c sustained a -min cardiac arrest due to tension pneumothorax seven days after ecmo decannulation. despite targeted temperature management, the patient experienced an anoxic cerebral injury that required prolonged rehabilitation. three months later, the patient returned home and was independent with several activities table . two reports have previously described attempts to rescue patients with refractory blastomycosis-related ards with ecmo. , resch et al. reported a case of a -yr-old previously healthy male with blastomycosis-related ards in germany. venovenous ecmo was initiated on the fourth day of illness; however, bilateral pneumothoraces and multi-system organ failure resulted in death on ecmo at day . due to a delay in diagnosis, antifungal therapy was initiated only on the final days in the course of the illness. dalton et al. reported a case of a -yr-old male with blastomycosis-related ards in which veno-arterial ecmo was initiated at day five of mechanical ventilation. although amphotericin b was initiated after approximately seven days of hospital contact, the patient developed progressive pulmonary necrosis and sustained a cardiac arrest due to bilateral tension pneumothoraces on ecmo day . a single reported case of central venoarterial ecmo for blastomycosis-related septic shock in a -yr-old was similarly unsuccessful. post-mortem specimens from affected patients have shown the classic pathologic features of ards, but they have also shown severe necrosis, abscess formation, hemorrhagic cysts, and invasive parenchymal destruction. , this raises the possibility that blastomycosis-related ards may be a uniquely severe disease entity due to virulence factors of an organism, pronounced host inflammatory response, or late recognition and treatment of the disease. it is possible that previous applications of ecmo in refractory blastomycosis-related ards failed due to delays in diagnosis and antimicrobial therapy or late initiation of extracorporeal support. , in contrast to previous reports, this case series describes the successful application of ecmo as a rescue therapy in blastomycosis-related ards. all patients in this series had severely impaired gas exchange, reduced pulmonary compliance, and rapid deterioration despite respiratory support consistent with the standard of care. extracorporeal membrane oxygenation facilitated improved gas exchange, as evidenced by increased p a o /f i o ratios and normalization of ph and p a co , and allowed lung rest as shown by reductions in potentially injurious airway pressures. although the therapy was resource intensive and necessitated prolonged admissions to hospital and the intensive care unit, in all four cases, ecmo decannulation ards = acute respiratory distress syndrome; ecmo = extracorporeal membrane oxygenation; f i o = fraction of inspired oxygen; p a o = partial pressure of oxygen; p a co = partial pressure of carbon dioxide; pbw = predicted body weight; peep = positive endexpiratory pressure ast = aspartate aminotransferase; ecmo = extracorporeal membrane oxygenation; f i o = fraction of inspired oxygen; p a co = partial pressure of carbon dioxide; p a o = partial pressure of oxygen; pbw = predicted body weight; peep = positive end-expiratory pressure; pip = peak inspiratory pressure; pplateau = plateau pressure; s v o = central venous oxygen saturation was performed, mechanical ventilation was withdrawn, and the patients were discharged home with acceptable quality of life. these outcomes are exceptional given the uniquely high mortality of blastomycosis-related ards. indications for ecmo among patients with ards are evolving. , , in addition to providing rescue therapy for patients with refractory hypoxemia, hypercapnia, or acidosis, when instituted early, ecmo may prevent ventilator-induced lung injury by allowing de-escalation of mechanical ventilatory support. , observational trials of ecmo among patients with ards due to h n virus have shown survival rates as high as %, though data from high-quality randomized controlled trials are lacking. with its inherently severe clinical course, blastomycosisrelated ards has thus been considered a therapeutic target for ecmo. maintaining a lung protective ventilation strategy may have greater clinical importance in this setting due to the pathologic severity of blastomycosisrelated ards. several factors may have contributed to the favourable outcomes in our cohort. first, diagnoses were made relatively early due to high clinical suspicion and experienced laboratory personnel. accordingly, appropriate antimicrobial agents were instituted early in the clinical course. it is well established that the administration of early appropriate antimicrobials reduces mortality in septic shock. second, ecmo support was initiated within hr in all patients. extracorporeal membrane oxygenation may confer greater therapeutic benefit in ards when initiated within seven days. , in addition, three patients in this series received early systemic corticosteroids, a therapy which may limit the inflammatory response and possibly reduce mortality in the paucity of published attempts at ecmo rescue in this setting may reflect clinicians' reluctance to apply ecmo in the context of septic shock and possible fungemia, both of which are considered relative contraindications to the use of ecmo. , we observed a decline in vasopressor requirement within the first - hr of ecmo support. although ecmo flows upon peripheral cannulation were - lÁmin - , this would not have matched patients' cardiac output prior to cannulation in the setting of septic shock, nor would ecmo be expected to deliver direct improvement in hemodynamics in a venovenous configuration. thus, we speculate that ecmo indirectly improved hemodynamics by improving oxygen delivery to vital organs and restoring physiologic acid-base balance. accordingly, ecmo may still have a therapeutic role in the setting of primary pulmonary disease with concomitant septic shock. our findings should be interpreted with several considerations. the previously reported mortality of blastomycosis-related ards largely reflects case series predating the arma study, representing an era in which lung protective ventilation was not standard practice. thus, with modern ventilatory strategies and possibly prone positioning, it is possible that more patients with blastomycosis-related ards may be salvageable and not require ecmo rescue. , our case series was small, retrospective, and lacked a control group; however, no patients referred for ecmo for pulmonary blastomycosis were refused during the study period. last, our aeromedical transport team provided several patients with early aggressive care and extracorporeal support. we acknowledge that our findings may lack generalizability because many centres lack such a service. extracorporeal membrane oxygenation may be an effective treatment modality for patients with blastomycosis-related ards and refractory hypoxemia despite optimal mechanical ventilation. early application of ecmo and timely appropriate antimicrobial therapy may contribute to favourable patient outcomes. when blastomycosis-related ards is identified or suspected, transport to an ecmocapable centre should be considered. epidemiology and clinical spectrum of blastomycosis diagnosed at manitoba hospitals acute respiratory distress syndrome and blastomycosis: presentation of nine cases and review of the literature endemic blastomycosis in mississippi: epidemiological and clinical studies corticosteroids for blastomycosis-induced ards: a report of two cases and review of the literature overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome blastomycosis in northeast tennessee extracorporeal life support for adults with severe acute respiratory failure extracorporeal membrane oxygenation for ards in adults efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for, influenza a(h n ) acute respiratory distress syndrome extracorporeal lung support for patients who had severe respiratory failure secondary to influenza a (h n ) infection in canada extracorporeal membrane oxygenation resuscitation in adult patients with refractory septic shock extracorporeal membrane oxygenation (ecmo) for severe acute respiratory distress syndrome (ards) in fulminant blastomycosis in germany extracorporeal membrane oxygenation for overwhelming blastomyces dermatitidis pneumonia central extracorporeal membrane oxygenation support for disseminated blastomycosis septic shock a systematic review to inform institutional decisions about the use of extracorporeal membrane oxygenation during the h n influenza pandemic duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock the italian ecmo network experience during the influenza a(h n ) pandemic: preparation for severe respiratory emergency outbreaks continuous cardiac output in septic shock by simulating a model of the aortic input impedance: a comparison with bolus injection thermodilution ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. the acute respiratory distress syndrome network prone positioning in severe acute respiratory distress syndrome reliability of the cerebral performance category to classify neurological status among survivors of ventricular fibrillation arrest: a cohort study acknowledgement the authors gratefully acknowledge the contributions of louise dyck who provided quality assurance regarding the reporting of technical aspects of ecmo conduct and equipment. disclosures no funding sources, commercial or non-commercial affiliations, associations, or consultancies apply to the corresponding author or author group. key: cord- -c kw f authors: baek, moon seong; lee, sang-min; chung, chi ryang; cho, woo hyun; cho, young-jae; park, sunghoon; koo, so-my; jung, jae-seung; park, seung yong; chang, youjin; kang, byung ju; kim, jung-hyun; oh, jin young; park, so hee; yoo, jung-wan; sim, yun su; hong, sang-bum title: improvement in the survival rates of extracorporeal membrane oxygenation-supported respiratory failure patients: a multicenter retrospective study in korean patients date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: c kw f background: although the utilization of extracorporeal membrane oxygenation (ecmo) is increasing and its technology is evolving, only a few epidemiologic reports have described the uses and outcomes of ecmo. the aim of this study was to investigate the changes in utilization and survival rate in patients supported with ecmo for severe respiratory failure in korea. methods: this was a multicenter study on consecutive patients who underwent ecmo across hospitals in korea. the records of all patients who required ecmo for acute respiratory failure between and were retrospectively reviewed, and the utilization of ecmo was analyzed over time. results: during the study period, patients received ecmo in korea as a whole, and a total of patients received ecmo at the participating hospitals. we analyzed ( . %) patients who received ecmo for respiratory failure. the number of ecmo procedures provided for respiratory failure increased from to during the study period. the in-hospital survival rate increased from . % to . %. the use of prone positioning increased from . % to . % (p < . ), and the use of neuromuscular blockers also increased from . % to . % (p < . ). multiple regression analysis showed that old age (or . ( % ci . , . )), use of corticosteroid (or . ( % ci . , . )), continuous renal replacement therapy (or . ( % ci . , . )), driving pressure (or . ( % ci . , . )), and prolonged ecmo duration (or . ( % ci . , . )) were associated with increased odds of mortality. conclusions: utilization of ecmo and survival rates of patients who received ecmo for respiratory failure increased over time in korea. the use of pre-ecmo prone positioning and neuromuscular blockers also increased during the same period. extracorporeal membrane oxygenation (ecmo), which provides respiratory and/or cardiac support, allows treatment of patients with refractory gas-exchange abnormalities [ ] . the use of ecmo to support patients with respiratory failure is increasing worldwide following the use of ecmo for severe acute respiratory failure during the influenza a pandemic [ ] [ ] [ ] [ ] . recently, the eolia trial reported that in patients with severe acute respiratory distress syndrome (ards) there was no significant difference in -day mortality between patients who received early ecmo and those who received conventional mechanical ventilation that included ecmo as rescue therapy [ ] . however, crossover to ecmo occurred in % of patients in the conventional group, who showed a high mortality rate of %. this suggests that ecmo can be used in severe ards patients who do not benefit from conventional treatment. survival of patients who received ecmo is also gradually increasing over time [ ] . a recent epidemiologic report in germany showed that ecmo utilization for severe respiratory failure significantly increased from until , and in-hospital survival increased over time as well [ ] . sauer et al. [ ] reported that the annual rates of ecmo cases increased by % from to in the united states, and that, albeit not statistically significant, there was an improving trend in the survival rate as well. in a single-center study in korea, the survival rates associated with the ecmo procedure increased between and [ ] . however, as we have previously reported, there was a discrepancy in the survival rate between those of the extracorporeal life support organization (elso) registry and korean ecmo patients [ ] . the in-hospital survival rate of ecmotreated patients with acute respiratory failure was % from to in korea, whereas the survival rate was % in the elso registry patients [ ] . also, we have suggested that age is an important factor in the survival of patients who received ecmo. therefore, we sought to determine whether there has been an improvement in the survival rate of patients who received ecmo support for acute respiratory failure in korea. specifically, we evaluated the changes over time in the survival rates of patients supported with ecmo for severe respiratory failure and the factors associated with the survival rate. this was a multicenter study of consecutive patients who received ecmo at hospitals in korea. the records of all patients who required ecmo for acute respiratory failure between and were retrospectively reviewed and the utilization of ecmo was analyzed over time. the decision to use ecmo was made at the discretion of the attending physicians at each center without standardization. the study protocol was approved by the institutional review board of asan medical center, and by the local institutional review boards of all other participating centers. the requirement for informed consent was waived due to the retrospective design of the study. data were collected from electronic medical records of patients older than years who received ecmo support. included variables were as follows: demographic information, acute physiology and chronic health evaluation (apache) ii and sequential organ failure assessment (sofa) scores at intensive care unit (icu) admission, etiology of respiratory failure, cardiac arrest, immunocompromised status, central nervous system (cns) dysfunction, pre-ecmo hemodynamic data, mechanical ventilation parameters, and arterial blood gas data. immunocompromised status and cns dysfunction were defined according to the resp study [ ] . immunocompromised status included hematological malignancies, solid tumors, solid-organ transplantation, high-dose or long-term corticosteroid and/or immunosuppressant use, and human immunodeficiency virus infection. cns dysfunction included diagnoses of neurotrauma, stroke, encephalopathy, cerebral embolism, seizure, and epileptic syndrome. we collected information on adjunctive therapy such as the use of vasopressors, steroids, continuous renal replacement therapy (crrt), prone positioning, nitric oxide, bicarbonate infusion, and neuromuscular blockers. we also collected data such as the ecmo mode, ecmo duration, duration of mechanical ventilation to ecmo initiation, hospital stay, and tracheotomy. the ecmo mode was categorized as veno-venous, veno-arterial, and veno-arteriovenous. outcome variables of the study were survival at discharge and ecmo weaning (survival within h after weaning from ecmo). demographics, pre-ecmo parameters, and outcomes were compared between and . differences with p < . were considered statistically significant. categorical variables are expressed as the number (percentage). continuous variables are expressed as the median (interquartile range). pearson's chi-square test or fisher's exact test was used to compare categorical data. the kruskal-wallis test was used to compare medians between groups. multiple logistic regression analysis using the backward elimination method was performed to identify the factors associated with survival at discharge. candidate variables for inclusion in the multiple logistic regression model were chosen from the univariate analysis; variables with p < . in the univariate analyses were included in the multivariate analysis, and collinearity was assessed before the multivariate analysis. calibrations of the models were evaluated with the hosmer-lemeshow goodness-of-fit test. statistical analyses were performed using the statistical package for the social sciences (spss) version . (ibm corporation, armonk, ny, usa). during the study period ( - ), patients received ecmo support in korea. ecmo support was given to patients in the participating hospitals. we analyzed ( . %) patients who received ecmo specifically for respiratory failure. the annual number of ecmo cases at institutions varied widely: eight centers had fewer than cases per year and the other eight survival prediction, arf acute respiratory failure, ards acute respiratory distress syndrome, copd chronic obstructive pulmonary disease, ild interstitial lung disease, cns central nervous system, crrt continuous renal replacement therapy, map mean arterial pressure, pao partial pressure of arterial oxygen, paco partial pressure of arterial carbon dioxide, hco − bicarbonate, sao oxygen saturation, fio fraction of inspired oxygen, peep positive endexpiratory pressure, pip peak inspiratory pressure, mv mechanical ventilation a "immunocompromised" included hematological malignancies, solid tumors, solid-organ transplantation, high-dose or long-term corticosteroid and/or immunosuppressant use, and human immunodeficiency virus infection b "cns dysfunction" included diagnoses of neurotrauma, stroke, encephalopathy, cerebral embolism, seizure, and epileptic syndrome centers had more than cases per year, with two of those centers having had more than cases per year. the patients' median age was years (range - years), and the median body mass index was . kg/m (range . - . kg/m ). pre-ecmo mechanical ventilation was provided in . % of patients and corticosteroid therapy was used in . % of patients. prone positioning was applied in . % of patients and neuromuscular blockers were used in . % of patients. the majority of patients were initially supported with veno-venous ecmo ( . %), and the median duration of support was days (interquartile range (iqr) , days). survival and weaning rates were . % and . %, respectively (table ) . the number of ecmo procedures for respiratory failure increased from to during the study period ( fig. ). there were no significant differences in age, sex, apache ii score, sofa score, immunocompromised status, cns dysfunction, cardiac arrest, crrt, use of nitric oxide and bicarbonate infusion, pao /fio ratio, ecmo duration, and duration of mechanical ventilation to ecmo initiation between groups. use of prone positioning increased from . % to . % (p < . ) and the use of neuromuscular blockers also increased from . % to . % (p < . ; table ). although the survival rate remained relatively low, it increased over time from . % to . % (p = . ; table ). post-hoc analysis showed that the survival rate in was significantly higher than the rates in and . factors associated with mortality in patients supported with ecmo multiple regression analysis was performed using age, sex, year, apache ii score, sofa score, immunocompromised status, cns dysfunction, corticosteroid, crrt, prone positioning, nitric oxide, neuromuscular blocker, . , . ) ), and prolonged ecmo duration (or . ( % ci . , . )) were associated with increased odds of mortality ( table ). the median age was older in the nonsurvivors ( years; iqr , years) than in survivors ( years; iqr , years) (p < . ). the survival rate decreased with age, with patients older than years having a survival rate of . % (fig. ) . ecmo duration was significantly longer in the nonsurvivors ( days; interquartile range (iqr) , days) than in survivors ( days; iqr , days) (p = . ). compared with the survival rate within weeks of ecmo support, the overall survival rate after weeks of ecmo support showed a significant decrease from . % to . % (p = . ). this multicenter study was conducted to evaluate the change in survival rates of patients who received ecmo support for acute respiratory failure in korea. utilization of ecmo for respiratory failure increased over time, and the survival rate was improved with increasing use of adjunctive management. also, patient age and the duration of ecmo were significantly associated with survival. a notable change during the study period was that the administration of neuromuscular blockades and use of prone positioning before ecmo had significantly increased from . % to . % and from . % to . %, respectively. papazian et al. [ ] reported that early use of neuromuscular blockades in patients with severe ards may improve survival. in the elso registry-based resp study, neuromuscular blockade agents before ecmo were independently associated with hospital survival [ ] . in addition, in patients with severe ards, early application of prolonged prone positioning was significantly associated with improved survival [ ] . schmidt et al. [ ] demonstrated that use of prone positioning before ecmo was also associated with survival. these results are in accordance with those in a recent systematic review and meta-analysis [ ] . moreover, for patients with severe ards, prone positioning before and during ecmo may be helpful for weaning from ecmo [ , ] . another distinctive finding was the change in pre-ecmo ventilator parameters. in recent years, the driving pressure was lower and minute ventilation was decreased. therefore, improvement in hospital survival of ecmo-supported patients with respiratory failure might be the result of increasing experience with ecmo over time, including evolving adjuvant therapies and improved management of mechanical ventilation. the results of this study showed that the number of ecmos carried out for respiratory failure increased from to from to , and that the in-hospital survival rate increased from . % to . % during the same period. the overall survival rate of % in "cns dysfunction" included diagnoses of neurotrauma, stroke, encephalopathy, cerebral embolism, seizure, and epileptic syndrome ecmo-supported respiratory failure patients in korea is lower than the reported rate of % in the elso registry [ ] . meanwhile, an ecmo epidemiologic study performed in germany reported that from to the in-hospital survival had steadily increased and the rate of survival was approximately %, which is similar to our findings [ ] . in addition, sauer et al. [ ] reported that in the united states the survival rate of the patients who received ecmo was approximately %. in the german study, approximately % of patients were older than years and increasing numbers of older patients had received ecmo. in the us study, the mean age of the patients who received ecmo was years, which is higher than that of the patients included in the elso registry. taken together, the discrepancies in demographics between the patients of ecmo centers not included in the elso and those in the elso registry may explain the difference in survival rates. also, another explanation for the relatively low survival rate of korean ecmo patients could be the infrequent use of prone positioning. the use of prone positioning and use of neuromuscular blockers were low compared with those in the eolia trial [ ] , in which prone positioning was applied in % of patients in the conventional ventilator support group, who showed a % survival rate. the relatively low survival rate in korean ecmo patients may be due to excessive use of ecmo in patients who may have shown good response to prone positioning. accordingly, the use of prone positioning is gradually increasing in korea. another interesting finding of our study was that the survival rate was associated with the ecmo duration. the survival rate of patients who required prolonged ecmo (longer than days) was significantly lower than that of patients who had shorter ecmo duration ( % vs %, respectively, p = . ). recently, posluszny et al. [ ] reported that ecmo duration was inversely correlated with the survival rate in ecmo-supported patients with respiratory failure; the survival rate in patients who had longer ecmo duration was % lower than that in those with shorter ecmo duration. nonetheless, the investigators suggested that prolonged ecmo was not futile because there was a significant improvement in survival from % to % in recent years. on the other hand, the aforementioned german epidemiologic study reported that prolonged ecmo was associated with poorer outcome; that the survival rate rapidly declined to % within days after ecmo initiation [ ] . therefore, further studies are needed to provide a more solid association between ecmo duration and the survival rate. our study has several limitations. this study was retrospective and had a relatively short study period. because not all patients treated with ecmo for respiratory failure in korea were included, selection bias is possible. in addition, long-term outcomes and quality of life could not be assessed, which warrants an extended observation period of our study populations or further epidemiologic studies. despite such limitations, our current multicenter study, which is not based on the elso registry, provides information on the change in the survival rate of ecmo patients with respiratory failure and the factors associated with survival, and adds to the understanding of survival in patients who receive ecmo due to respiratory failure. this multicenter study performed in korea showed that utilization of ecmo for respiratory failure had increased over time, and that the survival rates of ecmo-supported respiratory failure patients had improved with increasing utilization of adjunctive management. patient age and duration of ecmo were significantly associated with survival at discharge. extracorporeal membrane oxygenation for ards in adults extracorporeal membrane oxygenation for influenza a(h n ) acute respiratory distress syndrome extracorporeal membrane oxygenation for pandemic h n respiratory failure the italian ecmo network experience during the influenza a(h n ) pandemic: preparation for severe respiratory emergency outbreaks referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza a(h n ) extracorporeal membrane oxygenation for severe acute respiratory distress syndrome extracorporeal life support organization registry international report extracorporeal membrane oxygenation: evolving epidemiology and mortality extracorporeal membrane oxygenation use has increased by % in adults in the united states from the effect of an improvement of experience and training in extracorporeal membrane oxygenation management on clinical outcomes age is major factor for predicting survival in patients with acute respiratory failure on extracorporeal membrane oxygenation: a korean multicenter study predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. the respiratory extracorporeal membrane oxygenation survival prediction (resp) score neuromuscular blockers in early acute respiratory distress syndrome prone positioning in severe acute respiratory distress syndrome the preserve mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome prone positioning before extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: a retrospective multicenter study prone positioning during veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults outcome of adult respiratory failure patients receiving prolonged (>/= days) ecmo not applicable. this study was supported by a grant from the korea health technology r&d project through the korea health industry development institute funded by the ministry of health & welfare, republic of korea (hc c ). the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -d sid gd authors: varnholt, v.; lasch, p.; suske, g.; koelfen, w.; kachel, w. title: ards infolge schwerer rsv-infektion therapeutische optionen: therapeutische optionen date: journal: monatsschr kinderheilkd doi: . /s sha: doc_id: cord_uid: d sid gd we report on a strikingly frequent referral of former preterm babies with respiratory syncytial virus (rsv) infection and subsequent ards in our hospital during the winter / with regard to the clinical course under application of alternative treatment modalities. treatment modalities like inhalational ribavirin, use of bronchodilators and instillation of surfactant had been tried without success. all children (age: – months) were ventilated for . ( – ) days with fio( ) = . and a mean airway pressure of . ( – ) cm h( )o. mean arterial blood gases were (pao( )) and (pco( )) mm hg, the oi was . . by inhalational no in combination with ippv or hfov patients could be stabilized, in the other ecmo became necessary. two of them died in spite of several weeks on ecmo; children survived and could be discharged home after a mean hospital stay of months. even in very severe cases of rsv infection treatment modalities like no, hfov and ecmo can be used successfully. the use of these treatment modalities must be considered before the lung damage is irreversible; in those cases a pre-existing bpd is no contraindication even for extracorporeal lung support. infektionen mit dem respiratory syncytial virus (rsv) sind im sä uglingsund kleinkindalter die hä ufigste ursache fü r erkrankungen der tiefen atemwege: bronchiolitis und (broncho-) pneumonie [ ] . das rs-virus kommt in subtypen (a und b mit mehreren untergruppen) vor, von denen jeweils wä hrend einer saison (oktober-mä rz) dominiert [ ] . risikofaktoren fü r schwere verlä ufe (hospitalisierung, intensivtherapiestation, o -gabe, beatmung) sind: alter < wochen, zustand nach frü hgeburt, herzvitium, immundefekt und bronchopulmonale dysplasie [ ] . mit einfü hrung der ribavirinaerosolinhalation als kausale therapie sowie fortschritten in der pädiatrischen intensivmedizin sind lebensbedrohliche und letale verlä ufe bei rsv-infektionen in den letzten jahren sehr selten geworden [ , ] . wir berichten im folgenden ü ber eine auffallende hä ufung schwerster rs-virus-pneumonien mit konsekutivem ards im winterhalbjahr / in unserer klinik und den verlauf bei den betroffenen patienten -nach der vergeblichen anwendung "ü blicher" behandlungsmethoden -wä hrend der anwendung alternativer therapieverfahren [no-inhalation, hochfrequenzoszillationsbeatmung (hfov), extrakorporale membranoxygenierung (ecmo)]. im zeitraum von juli bis mä rz wurden patienten mit drohendem lungenversagen infolge schwerer rs-virus-pneumonie in unsere klinik verlegt, alle ü berwiesen von anderen kinderkliniken nach versagen konventioneller therapiemaßnahmen. vier kinder erkrankten noch wä hrend des postpartalen stationä ren aufenthalts, auch diese waren bei beginn der rs-virus-infektion extubiert und spontan atmend. die diagnose rsv-infektion wurde durch einen positiven qualitativen antigennachweis im nasen-oder rachenabstrich gesichert (schnelltest directigen r rsv; becton dickinson). bei kindern wurde eine bakterielle superinfektion (klebsiellen bzw. gramnegative stä bchen im trachealsekret) nachgewiesen. der ards-schweregrad wurde entsprechend dem score-system von murray et al. [ ] eingeschä tzt. [ ] , verwendet wurden die gerä te stephan (stephan/ gackenbach) und sensormedics a (sensormedics bv, bilthoven/nl). fü hrte auch diese nicht zu einer besserung, wurde die hfov mit no kombiniert. indikationen fü r die ecmo waren -nach scheitern aller vorangegangenen therapieverfahren einschließlich dem versuch der ventilation in bauchlage -eine akute hypoxie (pao < mm hg fü r > h bzw. pao < mm hg fü r > h) oder eine fehlende besserungstendenz nach mindestens sieben tagen maximalbeatmung [ ] . bevorzugte ecmo-technik war das venovenö se verfahren unter verwendung einer doppellumenkanü le [ ] . alle alternativen therapieverfahren (no, hfov, ecmo) wurden so lange angewandt, bis eine konventionelle beatmung mit atemwegsmitteldrü cken < cm h o und einem fio < , wieder mö glich war. die therapie der grundkrankheit wurde im wesentlichen unverä ndert fortgesetzt. die antibiotische behandlung bestand -bei zumindest initial meist fehlendem keimnachweis -aus einer dreier-kombination (vancomycin, azlocillin, gentamycin), ergä nzend wurden malig immunglobuline substituiert (falls in der verlegenden klinik noch nicht gegeben). angestrebt wurde ein hb-wert von g/dl, hierzu wurde -meist mehrfach -erythrozytenkonzentrat gegeben. sedierung we report on a strikingly frequent referral of former preterm babies with respiratory syncytial virus (rsv) infection and subsequent ards in our hospital during the winter / with regard to the clinical course under application of alternative treatment modalities. treatment modalities like inhalational ribavirin, use of bronchodilators and instillation of surfactant had been tried without success. all children (age: - months) were ventilated for . ( - ) days with fio = . and a mean airway pressure of . ( - ) cm h o. mean arterial blood gases were (pao ) and (pco ) mm hg, the oi was . . by inhalational no in combination with ippv or hfov patients could be stabilized, in the other ecmo became necessary. two of them died in spite of several weeks on ecmo; children survived and could be discharged home after a mean hospital stay of months. even in very severe cases of rsv infection treatment modalities like no, hfov and ecmo can be used successfully. the use of these treatment modalities must be considered before the lung damage is irreversible; in those cases a pre-existing bpd is no contraindication even for extracorporeal lung support. respiratory syncytial virus (rsv) -ards -inhaled nitric oxide (no) -high frequency oscillatory ventilation (hfov) -extracorporeal membrane oxygenation (ecmo) [ ] . nach -bis tägiger ecmo-therapie konnte bei von patienten erfolgreich dekanüliert werden, diese patienten ü berlebten. zwei kinder starben trotz -bzw. wö chiger ecmo-therapie infolge fehlender erholung der lungenfunktion, von ihnen erlitt unter ecmo einen hä morrhagischen hirninfarkt (einzige zerebrale komplikation aller ecmo-patienten). die gesamtletalitä t lag in unserem kollektiv somit bei %. die ü berlebenden kinder konnten alle extubiert und nach einem im mittel monatigen krankenhausaufenthalt nach hause entlassen werden. zwei kinder benö tigten infolge einer bpd sauerstoff auch nach der klinikentlassung, das neurologische follow-up (alter der kinder zum untersuchungszeitpunkt , - , jahre, - monate nach erkrankungsbeginn) ergab bei allen kindern eine leichte bis mä ßige entwicklungsretardierung in dem ausmaß, wie sie auch schon vor der rs-virus-erkrankung bestanden hatte. saisonale unterschiede in der häufigkeit und schwere von rs-virus-infektionen sind bekannt [ , , ] . wurden vor - jahren bei hospitalisierten risikokindern noch letalitä tsraten zwischen und % angegeben [ ] , verzeichnet eine neuere arbeit [ ] auch in einem hochrisikokollektiv nur noch eine sterblichkeit von , % (bei kindern mit pulmonaler vorerkrankung). diese deutlich verbesserte prognose ist einerseits auf die in den letzten jahren erzielten fortschritte im bereich der pä diatrischen intensivmedizin zurü ckzufü hren, andererseits auch auf die einfü hrung der ribavirininhalation als kausale therapie der rs-virus-infektion bei risikokindern [ ] . in etlichen fä llen hat allerdings die ribavirintherapie nur einen begrenzten oder keinen effekt [ , ] . von uns wurde -nach meist schon lä ngerem krankheitsverlauf und ausbildung eines ards -ribavirin nicht mehr eingesetzt, in den verlegenden kliniken nur in % der fä lle: von diesen wurde in keinem fall ü ber eine auch nur kurzfristige besserung berichtet. darü ber, ob die anderen kinder, fü r die ribavirin oder die apparatur zur anwendung des medikaments bei beatmungspatienten nicht zur verfü gung standen, von dessen einsatz profitiert hä tten, ist keine aussage mehr mö glich. auch andere therapiemaßnahmen (kortikosteroide, bronchodilatatoren, antibiotika, immunglobuline), die bei schweren rs-virus-pneumonien ü blicherweise [ ] wie bei unseren patienten (tabelle ) -zum einsatz kommen, kö nnen schwerste verlaufsformen nicht sicher verhindern. bronchodilatatoren abb. . krankheitsverlauf bei patienten mit rsv-pneumonie unter alternativen therapieverfahren wurden -in den verlegenden institutionen -in % der fä lle eingesetzt, nach Ü bernahme von uns nur noch bei kindern: die mö gliche obstruktive komponente einer rsv-infektion stand bei unseren patienten nicht im vordergrund, ersichtlich auch an den teilweise sehr niedrigen pco -werten. ob surfactantapplikationen, wie vorgeschlagen [ ] , beim pä diatrischen ards hilfreich sind, werden erst weitere beobachtungen zeigen: bei unserer patienten hatte die -mehrfache -surfactantinstillation allenfalls einen passageren positiven effekt. obwohl bei schwerer rsv-infektion mö glicherweise hilfreiche therapieverfahren nicht in allen fä llen zur anwendung kamen, ließ sich -in unserem kleinen kollektiv -anhand der beiden verstorbenen kinder keine maßnahme und kein medikament evaluieren, die letale verlä ufe verhindern kö nnten; auch eine prognostische aussage anhand der patientenvorgeschichte und des krankheitsverlaufs vor verlegung war nicht mö glich. mit steigender Ü berlebensrate sehr kleiner frü hgeborener wird die zahl von kindern mit chronischen pulmonalen erkrankungen noch zunehmen; diese haben ein sehr hohes risiko fü r virusinfektionen der unteren atemwege [ ] : % dieser kinder mü ssen in den ersten beiden lebensjahren deshalb rehospitalisiert werden. eine monatliche prophylaktische gabe von mit rsv-antikö rpern angereichertem immunglobulin an hochrisikokinder (ehemalige fg mit und ohne bpd) zeigte nur eine begrenzte schutzwirkung [ ] . so wird man auch in zukunft immer wieder kinder mit lebensbedrohlichen rs-virus-infektionen und nachfolgendem ards therapieren mü ssen, fü r welche konventionelle beatmungs-und behandlungsmethoden nicht ausreichen. dabei ist einschrä nkend festzustellen, daß die behandlung der schweren rsv-infektion und die beatmungsstrategie beim ards in verschiedenen institutionen unterschiedlich durchgefü hrt werden. auch bei durchsicht der krankenakten der verlegenden kliniken ließ sich nicht sagen, ob durch den frü heren einsatz einer modifizierten respiratortherapie (z. b. peep-erhö hung, irv-anwendung, ventilation in bauchlage) das schwere lungenversagen, das zur verlegung in unsere klinik fü hrte, hä tte verhindert werden kö nnen. positiv ist zu vermerken, daß exzessive beatmungsspitzendrü cke und zu hohe atemzugvolumina (gefahr der baro-und volutraumatischen lungenschä digung) meist vermieden wurden ( tabelle ) . die extrakorporale membranoxygenierung (ecmo), seit erfolgreich bei pphn-assoziierten erkrankungen des neugeborenen eingesetzt, wird seit den frü hen er jahren auch beim schweren lungenversagen des kindes angewandt. steinhorn u. green [ ] durch hfov kann -ebenso wie bei der pphn im neugeborenenalter -beim kindlichen lungenversagen eine ausreichende oxygenierung auch nach dem scheitern einer konventionellen beatmung erreicht werden [ , ] . gutierrez et al. [ ] berichteten ü ber erfolgreich mit hfov behandelte sä uglinge mit rsv-infektion. trotzdem muß auch bei der hfov mit therapieversagern gerechnet werden: arnold et al. [ ] berichteten ü ber eine mortalitä t von % (ohne ecmo-backup): bei unseren patienten zeigte nur von eine dauerhafte verbesserung seiner respiratorischen situation unter hfov, weitere besserten sich immerhin vorü bergehend. eine weitere mö glichkeit bei der behandlung des kindlichen lungenversagens stellt die kombination von hfov mit no dar: die vorteile beider therapieverfahren (rekrutierung und beibehaltung eines optimalen lungenvolumens unter vermeidung hoher beatmungsspitzendrü cke bei gleichzeitiger senkung des pulmonalen widerstands und damit besserer alveolä rer durchblutung) kö nnen gleichzeitig genutzt werden. dies wurde in fall (ehemaliges frü hgeborenes der . ssw mit rsv-pneumonie) schon beschrieben [ ] und fü hrte auch bei unserer patienten zu einer dauerhaften besserung. durch den einsatz von no oder/und hfov kann bei schwer verlaufenden rsv-infektionen -wie bei anderen formen des kindlichen lungenversagens -eine ecmo-therapie manchmal vermieden werden. ob zuerst die no-inhalation oder die oszillationsbeatmung zur anwendung kommen sollte, lä ßt sich nach dem gegenwä rtigen wissensstand nicht eindeutig beantworten: die anwendung der hfov beinhaltet mehrere risiken [ ] ; die no-applikation verlä uft -wie auch bei un-seren patienten -zwar meist kompli- acute effects of inhaled nitric oxide in children with severe hypoxemic respiratory failure prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure zur epidemiologie und therapie der rs-virusinfektion high frequency ventilation respiratory syncytial virus infection in children with bronchopulmonary dysplasia die rolle des respiratory-syncytial-virus-immunglobulins (rsvig) in der prä vention von rs-virusinfektionen bei hochrisikokindern successful high-frequency oscillatory ventilation in small infants with respiratory syncytial virus infection. th conference on high-frequency ventilation of infants respiratory syncytial virus puzzle: clinical features, pathophysiology, treatment, and prevention extrakorporale membranoxygenierung mit venovenö ser doppel-lumen-kanü len-technik respiratory syncytial virus infection in children surfactantbehandlung des respiratorischen versagens im kindesalter jenseits der neugeborenenperiode die behandlung der persistierenden pulmonalen hypertonie des neugeborenen (pphn) durch stickoxidinhalation (no) an expanded definition of the adult respiratory distress syndrome improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of canadian children pediatric ecmo registry of the extracorporeal life support organization (elso) a controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection use of extracorporeal membrane oxygenation in the treatment of respiratory syncytial virus bronchiolitis: the national experience, to treatment of respiratory failure in an infant with bronchopulmonary dysplasia infected with respiratory syncytial virus using inhaled nitric oxide and high frequency ventilation hochfrequenzoszillationsbeatmung bei sä uglingen mit schwersten atemstö rungen: mö glichkeiten kationslos [ ] , jedoch bildet sich häufig eine tage bis wochen bestehende no-abhä ngigkeit der patienten aus, ü ber deren mö gliche gefä hrdung durch langdauernde no-anwendung noch zu wenig bekannt ist [ ] .unserer ansicht nach haben alle alternativen therapieverfahren (hfov, no, ecmo) ihre berechtigung bei der behandlung des schweren kindlichen lungenversagens. wann welche therpaie zum einsatz kommen sollte, ist je nach dem klinischen zustand des patienten zu entscheiden; bei nicht akuter hypoxie kann aber mit dem einsatz von ecmo etwa woche lang abgewartet werden, ob nicht mit anderen maßnahmen eine besserung eintritt [ ] . dann aber sollte -vor dem eintritt einer irreversiblen lungenschädigung -ü ber eine verlegung in ein ecmo-zentrum entschieden werden: die beiden todesfä lle in unserem kollektiv mit rsv-pneumonie traten bei den kindern auf, die erst nach -bzw. tä giger vorbeatmungszeit zu uns verlegt worden waren.kinder mit schwerer rsv-infektion und nachfolgendem ards unterscheiden sich von anderen ards-patienten, fü r welche konventionelle beatmungs-und behandlungsmethoden nicht mehr ausreichen, durch jü ngeres alter bei erkrankungsbeginn, hä ufig zustand nach frü hgeburt mit postpartaler respiratortherapie sowie eine insgesamt bessere Ü berlebensrate [ ] . eine vorbestehende bpd stellt keine kontraindikation fü r den einsatz von hfov, no und ecmo dar, wie unsere ergebnisse und berichte in der literatur [ , , , ] belegen (allerdings ist mit langwierigen verläufen und einem mehrwö chigem bis evtl. mehrmonatigem klinikaufent-halt zu rechnen). ob bei beatmungspflichtigen kindern mit rsv-pneumonie ein frü herer einsatz von no und/oder hfov zu einer weiteren senkung der letalität fü hrt, mü ssen weitere beobachtungen zeigen. key: cord- -ml mgyf authors: huang, linna; zhang, wei; yang, yi; wu, wenjuan; lu, weihua; xue, han; zhao, hongsheng; wu, yunfu; shang, jia; cai, lihua; liu, long; liu, donglin; wang, yeming; cao, bin; zhan, qingyuan; wang, chen title: application of extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome induced by avian influenza a (h n ) viral pneumonia: national data from the chinese multicentre collaboration date: - - journal: bmc infect dis doi: . /s - - -x sha: doc_id: cord_uid: ml mgyf background: evidence concerning the efficacy and safety of extracorporeal membrane oxygenation (ecmo) in patients with influenza a (h n ) has been was limited to case reports. our study is aimed to investigate the current application, efficacy and safety of ecmo in for severe h n pneumonia-associated acute respiratory distress syndrome (ards) in the chinese population. methods: a multicentre retrospective cohort study was conducted at hospitals that admitted patients with avian influenza a (h n ) viral pneumonia patients’ admission from provinces in china between october , , and march , . data from the national health and family planning commission of china, including general conditions, outcomes and ecmo management, were analysed. then, successfully weaned and unsuccessfully weaned groups were compared. results: a total of patients, aged ± years, were analysed; . % of patients were male with % mortality. all patients underwent invasive positive pressure ventilation (ippv), and rescue ventilation strategies were implemented for cases ( . %) with an average ippv duration of ± d, pao( )/fio( ) of ± mmhg, tidal volume (vt) of ± ml and plateau pressure (p(plat)) of ± cmh( )o pre-ecmo. after h on ecmo, pao( ) improved from ± mmhg to ± mmhg and paco( ) declined from ± mmhg to ± mmhg. haemorrhage, ventilator-associated pneumonia (vap) and barotrauma occurred in . %, % and . % of patients, respectively. compared with successfully weaned patients (n = ), the unsuccessfully weaned patients had a longer duration of ippv pre-ecmo ( ± d vs. ± d, p < . ) as well as a higher p(plat) ( ± cmh( )o vs. ± cmh( )o, p < . ) and vt ( ± ml vs. ± ml, p < . ) after h on ecmo support. furthermore, the unsuccessfully weaned group had a higher mortality ( % vs. . %, p < . ) with more haemorrhage ( . % vs. . %, p < . ). conclusions: ecmo is effective at improving oxygenation and ventilation of patients with avian influenza a (h n ) induced severe ards. early initiation of ecmo with appropriate ippv settings and anticoagulation strategies are necessary to reduce complications. conclusions: ecmo is effective at improving oxygenation and ventilation of patients with avian influenza a (h n ) induced severe ards. early initiation of ecmo with appropriate ippv settings and anticoagulation strategies are necessary to reduce complications. keywords: extracorporeal membrane oxygenation (ecmo), avian influenza a (h n ), acute respiratory distress syndrome (ards), complications, mortality background avian influenza a (h n ) viral pneumonia can manifest with varying degrees of dyspnea and is associated with a mortality of~ % [ ] . in particular, % of patients develop rapidly progressive pneumonia and % progress to acute respiratory distress syndrome (ards). the mortality of severe ards is as high as % [ ] . timely and effective respiratory support is particularly important to treat severe ards caused by avian influenza a (h n ) pneumonia. however, severe ards induced by avian influenza a (h n ) pneumonia might manifest as refractory hypoxaemia even with appropriate invasive positive pressure ventilation (ippv) support. extracorporeal membrane oxygenation (ecmo) is the ultimate respiratory support method and directly improves the oxygenation and ventilation of patients as well as enables implementation of the "lung protective ventilation strategy" [ ] . ecmo was the breakthrough treatment for the severe avian influenza a (h n ) outbreak of and reduced mortality from this outbreak [ ] [ ] [ ] . therefore, we believe that ecmo could also be effective for other types of severe viral pneumonia. existing studies of ecmo treatment for avian influenza a (h n ) pneumonia are primarily limited to case reports [ ] [ ] [ ] , and no study has systematically reviewed the efficacy or safety of ecmo to treat such diseases. therefore, it is particularly important to understand the current application of ecmo for avian influenza a (h n ) pneumonia-induced severe ards, investigate the application timing and management strategies of ecmo, and explore the possible reasons for treatment failure. based on the current study, we expect to standardize the management of ecmo and provide a description of our experiences using ecmo to treat patients with avian influenza a (h n ) pneumoniainduced severe ards. patients who had laboratory-confirmed avian influenza a (h n ) virus-induced pneumonia were included in this study. patients were admitted to hospitals in provinces of china between october , , and march , , and were reported to the national health and family planning commission of china. we included patients aged > ys who were supported by ecmo. patients who were lacking key detailed records of parameters during ecmo, such as ventilator or laboratory findings, were excluded. the included patients were divided into groups, namely, the "successfully weaned group" and "unsuccessfully weaned group". the former refers to a group of patients whose condition improved and were weaned from ecmo for at least h; the "unsuccessfully weaned group" refers to those who died or voluntarily discontinued treatment due to lack of improvement during ecmo support. the general conditions included age, gender, pregnancy status, underlying disease, time from onset to antiviral drug administration, vasoactive drug administration pre-ecmo, duration of ippv pre-ecmo, whether rescue ventilation strategies (including lung recruitment maneuvre, prone-position ventilation, and high-frequency oscillation ventilation) were implemented pre-ecmo, disease severity score, total duration of ecmo and ippv. we collected the ecmo blood flow at , , , and h on ecmo. improvement in circulatory and respiratory physiological indicators were considered, as well as ippv parameters at h pre-ecmo and , , and h on ecmo. furthermore, anticoagulation indicators during ecmo, including the types of anticoagulant drugs and methods of use; the maximum and minimum values of the activated coagulation time (act) and activated partial thromboplastin time (aptt); and the differences between the maximum and minimum act and aptt at , , and h on ecmo were recorded. finally, data regarding complications during ecmo therapy, including ecmo and ippv-related complications and nosocomial infections, were collected. the primary outcome was in-hospital mortality. the secondary outcomes were the length of stay in the intensive care unit (icu) and total length of hospitalization. three methods were used for a laboratory diagnosis, namely, the real-time reverse transcription-polymerase chain reaction (rt-pcr), viral isolation, and serological testing for the avian influenza a (h n ) virus using a modified haemagglutinin inhibition assay [ ] [ ] [ ] . we defined ards according to the berlin definition in [ , ] . pneumonia was diagnosed as an acute illness with fever, cough, or dyspnea/tachypnea, and at least one new focal chest sign that was supported by a finding of lung shadowing on a chest radiograph and without other noninfectious causes. the primary criteria for severe pneumonia were as follows: < > need for tracheal intubation and mechanical ventilation (mv) and < > need for vasoactive drugs after the active fluid resuscitation due to septic shock. the secondary criteria were as follows: < > respiratory rate ≥ times/ min; < > pao /fio ≤ mmhg; < > multiple lobe infiltration; < > disturbances of consciousness, disorientation, or both; < > blood urea nitrogen ≥ . mmol/l; and < > systolic blood pressure ≤ mmhg that required active fluid resuscitation. patients who met one primary criterion or at least three secondary criteria were diagnosed as having severe pneumonia [ ] . the criteria for the diagnosis of vap are in accordance with the european centre for disease prevention and control [ ] and included the following: < > two or more sequential chest x-rays or ct scans with a suggestive image of pneumonia for patients with underlying cardiac or pulmonary disease, or one definitive chest x-ray or ct scan in patients without underlying cardiac or pulmonary disease; < > a fever greater than °c and/ or leukocytosis greater than or equal to , wbc/ mm or leukopenia less than or equal to wbc/ mm ; and < > at least one of the following: <a > new onset of purulent sputum or change in the characteristics of the sputum; <b > cough, dyspnea, or tachycardia; <c > auscultatory findings, such as rales, bronchial breath sounds, ronchi, or wheezing; or <d > worsening gas exchange (e.g., oxygen desaturation or increased oxygen requirements or increased ventilation demand). for all included patients, we first described the general conditions, ecmo model and parameters, ippv parameters, the changes in circulation and respiratory physiological indicators from pre-ecmo to on ecmo status, anticoagulation on ecmo, and complications during ecmo therapy in all included patients. then, we compared patients who were successfully or unsuccessfully weaned from ecmo with regard to above items. all of the analyses were performed using spss . software. normally distributed continuous variables are expressed as the means ± sd and were compared using the t-test or chi-square test. non-normally distributed continuous variables are expressed as medians and quartiles and were compared using the wilcoxon rank-sum test. categorical variables were compared using the x test. p-values < . were considered significant. a total of patients were diagnosed with avian influenza a (h n ) virus-related pneumonia. patients were admitted to hospitals in provinces of china between october , , and march , , and were reported to the national health and family planning commission of china. the medical records of patients were available, and patients were reported to be supported by ecmo. one of the patients lacked ippv and ecmo parameters pre-ecmo and on ecmo and was eliminated as a participant; therefore, patients were ultimately selected ( fig. ) . data from patients ( . % males), with an average age of ± years, were analysed. there was no patient under the age of . a total of patients had underlying diseases, patients were treated with steroids and immunosuppressive agents within month of admission to the hospital, and patient was pregnant. the sequential organ failure assessment (sofa) score was ± points, and the murray score was . ± . points. the time from onset to antiviral drug administration was approximately ± d, and the time from onset to ecmo support was approximately ± d. high-dose vasoactive drugs [ ] were needed to maintain blood pressure in patients ( . %). the duration of ippv pre-ecmo was approximately ± d. rescue ventilation strategies, including the recruitment manoeuvre (rm), prone-position ventilation (pp) and high frequency oscillatory ventilation (hfov), were needed for patients ( . %) pre-ecmo. the total durations of ippv and ecmo were approximately ± d and d ( - d), respectively. of the patients, ( %) were successfully weaned from ecmo, and the other patients died due to an uncontrolled haemorrhage ( patients), septic shock ( patients due to progressive lung infection, patients due to bloodstream infection), heart failure ( patients) and discontinuation of treatment because of no improvement ( patients). one of patients showed an aggregated lung infection after weaning and eventually died due to septic shock. the inhospital mortality was %. the length of icu stay was ± d, and the total length of hospitalization was ± d (table ) . of the patients, were treated using the veno-venous ecmo (v-v ecmo) model. a total of patients with severe cardiac insufficiency and cardiogenic shock were treated using the venous-arterial ecmo (v-a ecmo) model. the ecmo equipment was mainly provided by maquet (shanghai) medical equipment co., ltd. and sorin (shanghai) medical equipment co., ltd. the pump from sorin was the stockert centrifugal pump system (scp/scpc), and the oxygenator was the d eos ecmo. the pump from maquet was the rota-flow, and the oxygenator was the quadrox pls. changes in ippv parameters and physiological indicators in patients on ecmo the ventilator parameters, including fio , positive end-expiratory pressure (peep), p plat , and vt, were significantly decreased in patients on ecmo. the vital signs, which included the heart rate, respiratory rate, and spo , and the arterial blood gas analysis (abg), which included the ph, paco , and pao levels, were improved in patients after ecmo support ( table ) . monitoring of anticoagulation all patients received a continuous infusion of unfractionated heparin for anticoagulation. however, heparin was discontinued for patients with cerebral haemorrhage and with active gastrointestinal haemorrhage. the act was ± to ± s at h, ± to ± s at h, and ± to ± s at h on ecmo. the aptt was ± to ± s and ± to ± s at and h on ecmo, respectively. complications during ecmo therapy in this study, the rates of gastrointestinal haemorrhage, cerebral haemorrhage, brain death, renal insufficiency, disseminated intravascular coagulation (dic), hyperglycaemia, and ecmo oxygenator thrombosis were higher compared to the relevant data from the ecls registry report [ , ] . new cases of vap developed in patients during ecmo, with an incidence rate of %. new cases of barotrauma occurred in patients, accounting for . % of cases. in addition, patients had a urinary infection, with an incidence rate of . %, and patients had a catheter-related blood stream infection (crbsi), with an incidence rate of . % (table ) . comparison between the patients successfully and unsuccessfully weaned from ecmo group contained patients who were successfully weaned from ecmo, and group included patients who were unsuccessfully weaned from ecmo. compared with patients successfully weaned from ecmo, the unsuccessfully weaned group had a higher mortality ( % vs. . %, respectively, p < . ), and was older ( ± years vs. ± years, respectively, p = . ), and more likely to have diabetes mellitus ( . % vs. . %, respectively, p < . ), had more frequent severe conditions (sofa: ± points vs. ± points, respectively, p < . ) pre-ecmo. meanwhile, they had a longer duration of ippv ( ± d vs. ± d, respectively, p < . ), had lower pao /fio levels ( . ± . mmhg vs. . ± . mmhg, respectively, p < . ), and higher rate of rescue ventilation strategies ( % vs. . %, respectively, p < . ) before ecmo support. no significant differences were found in the total duration of ippv, total duration of ecmo, length of icu stay and length of hospitalization between the two groups (table ) . ecmo blood flow did not significantly differ between the two groups during the initiation of ecmo support. however, in the successfully weaned group vs. the unsuccessfully weaned group, a significant decrease in blood flow correlated with an increase in the duration of support, which was . ± . l/min vs. . ± . l/min, respectively, (p < . ) at h on ecmo and . ± . l/ min vs. . ± . l/min, respectively, (p < . ) at h on ecmo (additional files and ). in the successfully weaned group compared to the unsuccessfully weaned group, fio was ± % vs. ± (fig. , additional file ). the vital signs were improved but did not significantly differ between the two groups pre-ecmo and during ecmo support (additional file ). patients who were unsuccessfully weaned from ecmo compared to patients who were successfully weaned from ecmo had severe acidosis (ph: . ± . vs. . ± . , respectively, (p < . ), a higher paco ( . ± . mmhg vs. . ± . mmhg, respectively, (p < . ), and a higher lactate concentration ( . ± . mmol/l vs. . ± . mmol/l, p < . ) pre-ecmo. ph and paco did not differ significantly between the two groups during ecmo support, while patients who were eventually successfully weaned from ecmo had a gradual ascending tendency of pao at and h on ecmo and a sustained low level of lactate (fig. , additional file ) . during the early stage of ecmo ( and h), the successful weaning group showed smaller differences between the act max and act min than the unsuccessful weaning group, which was ± s vs. ± s at h (p < . ) and ± s vs. ± s at h (p < . ). however, this trend was not found with regard to the difference between the maximum and minimum aptt. there were no differences between the two groups in mechanical complications associated with ecmo, vap and barotrauma. the successfully weaned group compared to the unsuccessfully weaned group had a lower haemorrhage rate ( . % vs. . %, respectively, p < . ), lower rate of renal insufficiency ( . % vs. . %, respectively, p < . ), lower rate of liver failure ( % vs. . %, respectively, p < . ) and lower heart failure rate ( . % vs. . %, respectively, p < . ). this study was the first to systematically and comprehensively discuss as well as elaborate on the current application of the efficacy and safety of ecmo in patients with h n pneumonia-related ards. a few studies [ , , , ] have shown that the mortality of ph n -induced ards was reduced to - % following ecmo treatment. presently, no studies with large samples have investigated the mortality of h n -induced ards, while the in-hospital mortality was as high as % in our study. late initiation of ecmo, inappropriate ippv settings during ecmo, and more ecmo complications might explain the relatively high mortality. moreover, as a multicentre collaboration study, the experiences of ecmo varied among the centres (additional file ), which might be another reason for the high mortality. according to the extracorporeal life support organization (elso) data [ , ] , ecmo is indicated when death risk exceeds %, i.e., when pao /fio < mmhg on fio > % and the murray score is - . our patients met the indications for ecmo support. the duration of mv for more than days pre-ecmo is an important prognostic factor for death [ ] . for patients in the successfully weaned group, the duration of ippv pre-ecmo was ± d; however, the duration was even longer among patients in the unsuccessfully weaned group ( ± d). moreover, rescue ventilation strategies were implemented for most patients before ecmo, which partially delayed the timing of ecmo. in comparison, ecmo was initiated at h ( - h) after ippv among patients with ph n in australia and new zealand in [ ] , which was significantly shorter than that in our cases. therefore, we emphasized early implementation of ecmo in our patients. the principle of ippv during ecmo is the "lung rest strategy" [ ] . the reva registry study examined patients with ph n -induced ards [ ] and showed that the high p plat ( cmh o) on day of ecmo was related to high mortality. in our study, the pre-ecmo p plat level was high ( ± cmh o). high p plat can lead to overdistension of the alveoli and cause lung volutrauma. the shear force between the overdistended and collapsed alveoli further aggregates vili [ ] , which ultimately increases mortality. although the p plat values [ ] showed that a high peep level within d of being on ecmo was related to decreased mortality. although no difference was observed in the peep levels between the two groups, we speculated that the down-regulation of peep during ecmo might have further aggravated the occurrence of collapse-induced injury, which led to atelectasis and sputum discharge obstacles. therefore, the ippv parameters, including high p plat and vt levels and low peep settings, might have been unreasonable in our study; lung rest or the maintenance of open alveoli was not achieved. the incidence of an ecmo oxygenator thrombus, haemorrhage, and organ failure in our study was high, which suggests that some problems existed in the anticoagulation management and organ supportive treatment of ecmo. we found that the unsuccessfully weaned group had larger fluctuations in act (the difference between act max and act min were larger) during the early stage of anticoagulation. this effect might suggest relatively unstable anticoagulation and a higher risk of haemorrhage. moreover, the incidence rate of vap during ecmo was as high as % and was partially attributed to the long course of h n pneumonia and the prolonged duration of ippv. therefore, intensification of airway management was extremely necessary. our study had limitations. the nature of the study required the collection of data at multiple consecutive time points to evaluate the efficacy of ecmo. as a retrospective study with some missing data, we were unable to successfully collect data at h pre-ecmo and , , and h post-ecmo. additionally, the number of subjects was too small to perform a multiple regression analysis to explore the risk factors for unsuccessful weaning from ecmo. ecmo is effective at improving oxygenation and ventilation of patients with avian influenza a (h n )-induced severe ards. early initiation of ecmo with appropriate ippv settings and anticoagulation strategies are necessary to reduce complications. fig. comparison of ippv parameters and abgs between two groups of patients on ecmo. for the successfully weaned group compared to the unsuccessfully weaned group, fio was ± % vs. ± %, respectively, at h (p < . ) and ± % vs. ± %, respectively, at h (p < . ). the monitored p plat was ± cmh o vs. ± cmh o, respectively, at h (p < . ) and ± cmh o vs. ± cmh o, respectively, at h (p < . ). the monitored vt was ± ml vs. ± ml, respectively, at h (p < . ) and ± ml vs. ± ml, respectively, at h (p < . ) after ecmo support. however, there were no differences in peep during ecmo between the two groups. patients who were in the unsuccessfully weaned group compared to patients in the successfully weaned group had severe acidosis (ph: . ± . vs. . ± . , respectively, (p < . ), a higher paco ( . ± . mmhg vs. . ± . mmhg, respectively, (p < . ), and a higher lactate concentration ( . ± . mmol/l vs. . ± . mmol/l, respectively (p < . ), pre-ecmo. the ph and paco did not significantly differ between the two groups during ecmo therapy, while patients who eventually weaned successfully from ecmo had a gradual ascending tendency in pao at and h on ecmo and a sustained low level of lactate after ecmo therapy people's republic of china. department of intensive care unit, the first affiliated hospital of wannan medical college people's republic of china. department of intensive care unit clinical findings in cases of influenza a (h n ) virus infection the new definition for acute lung injury and acute respiratory distress syndrome: is there room for 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a (h n ) viral pneumonia epidemiology of human infections with avian influenza a (h n ) virus in china human infection with a novel avian-origin influenza a (h n ) virus acute respiratory distress syndrome: the berlin definition the berlin definition of ards: an expanded rationale, justification, and supplementary material guidelines for the management of adult lower respiratory tract infections-summary surveillance of nosocomial infections in intensive care units: hos-pital in europe link for infection control through surveillance (helics) (versión . extracorporeal membrane oxygenation for influenza-associated acute respiratory distress syndrome fifty years of research in ards. is extracorporeal circulation the future of acute respiratory distress syndrome management? extracorporeal life support organization registry report use of extracorporeal life support to support patients with acute respiratory distress syndrome due to h n / influenza and other respiratory infections extracorporeal membrane oxygenation for acute respiratory distress syndrome: is the configuration mode an important predictor for the outcome? extracorporeal lung support for patients who had severe respiratory failure secondary to influenza a (h n ) infection in canada extracorporeal life support organization registry report extracorporeal life support organization registry international report extracorporeal life support for severe acute respiratory distress syndrome in adults extracorporeal membrane oxygenation in adult patients with acute respiratory distress syndrome mechanical ventilation in ards: one size does not fit all mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study not applicable. dr. zhan was supported by a grant from the national key research and development programme-major chronic non-communicable diseases' prevention and control (qml yfc ). dr. cao was supported by a grant from the national science fund for distinguished young scholars (grant number /h ) and grants from the national natural science foundation of china ( / h and /h ), and the national program for the prevention and control of human infections by avian-origin h n influenza a virus (kjyj- - - ). the funding sources had no role in the design, conduct, or reporting of the study or the decision to submit the manuscript for publication. the remaining authors have disclosed that they do not have any potential conflicts of interest. the datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. department of infectious diseases, henan provincial people's hospital, zhengzhou, henan province, people's republic of china. additional file : blood flow during ecmo, changes in ippv parameters and physiological indicators pre-ecmo and during ecmo. (docx kb) additional file : blood flow during ecmo between the two groups. in the successfully weaned group vs. the unsuccessfully weaned group, a significant decrease in ecmo blood flow correlated with an increase in the duration of support, which was . ± . l/min vs. . ± . l/ min, respectively, at h (p < . ) and . ± . l/min vs. . ± . l/ min, respectively, at h (p < . ). (tiff kb) additional file : changes in vital signs pre-ecmo and during ecmo between the two groups. vital signs were improved and did not significantly differ between the two groups during ecmo. authors' contributions all authors made substantial contributions to the conception and design of the study, data acquisition, analysis or interpretation of data, and review and approval of the final manuscript. drs. lh, wz, yy, ww and wl contributed equally to the article. drs. bc and qz assumed full responsibility for the integrity of the submission and publication and were involved in the study design. drs. wz, yy, ww, wl, hx, hz, yunfu wu (yw), js, lc, and ll were responsible for caring for the influenza a (h n ) cases and have been involved in gathering data. drs. lh, bc, qz, cw, dl, and yw had full access to all of the data in the study, assume responsibility for the integrity of the data and the accuracy of the data analysis and were responsible for data verification and analysis, as well as the drafting of the manuscript.ethics approval and consent to participate all patients gave written informed consent before ecmo treatment. as a highly pathogenic disease, the chinese national health and family planning commission approved the collection of the data from the patients with h n virus-induced pneumonia. the informed consent was waived to allow for exploration of the characteristics of the emerging infectious disease after rigorous contemplation and discussion by the chinese national health and family planning commission. not applicable. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. submit your next manuscript to biomed central and we will help you at every step: key: cord- -x jyu z authors: ko, ryoung-eun; lee, jin gu; kim, song yee; kim, young tae; choi, sun mi; kim, do hyung; cho, woo hyun; park, seung-il; jo, kyung-wook; kim, hong kwan; paik, hyo chae; jeon, kyeongman title: extracorporeal membrane oxygenation as a bridge to lung transplantation: analysis of korean organ transplantation registry (kotry) data date: - - journal: respir res doi: . /s - - - sha: doc_id: cord_uid: x jyu z background: the use of extracorporeal membrane oxygenation (ecmo) as a bridge to lung transplantation has greatly increased. however, data regarding the clinical outcomes of this approach are lacking. the objective of this multicenter prospective observational cohort study was to evaluate lung transplantation outcomes in korean organ transplantation registry (kotry) patients for whom ecmo was used as a bridge to transplantation. methods: between march and december , a total of patients received lung transplantation and were registered in the kotry, which is a prospective, multicenter cohort registry. the entire cohort was divided into two groups: the control group (n = , . %) and bridge-ecmo group (n = , . %). results: there were no significant differences in pre-transplant and intraoperative characteristics except for poorer oxygenation, more ventilator use, and longer operation time in the bridge-ecmo group. the prevalence of primary graft dysfunction at , , , and h after transplantation did not differ between the two groups. although postoperative hospital stays were longer in the bridge-ecmo group than in the control group, hospital mortality did not differ between the two groups ( . % vs. . %, p = . ). the majority of patients ( . % of the bridge-ecmo group and . % of the control group) were discharged directly to their homes. finally, the use of ecmo as a bridge to lung transplantation did not significantly affect overall survival and graft function. conclusions: short- and long-term post-transplant outcomes of bridge-ecmo patients were comparable to recipients who did not receive ecmo. lung transplantation has become an accepted treatment for carefully selected patients with end-stage lung disease [ , ] . however, due to a shortage of donors, the number of patients on waiting lists is growing rapidly and the average waiting time to lung transplantation has increased [ , ] . given these circumstances, there has been a corresponding increase in demand for mechanical ventilation (mv) and extracorporeal membrane oxygenation (ecmo) support to bridge these critically ill patients to lung transplantation. mv is associated with risks of ventilator-associated pneumonia, ventilator-induced lung injury, and hemodynamic instability [ ] [ ] [ ] [ ] . furthermore, recent reports have indicated that waiting for lung transplantation with mv support is a risk factor for increased mortality compared without mv [ , ] . recently, due to advances in critical care management and improvements in technology regarding the safety profile and management of ecmo, the use of ecmo as a bridge to lung transplantation has steadily increased [ ] [ ] [ ] . however, bridging to transplantation with ecmo has also been associated with major complications and increased in-hospital mortality [ , ] . in addition, ecmo is invasive, requires anticoagulation for the duration of therapy, and can be associated with serious complications [ , ] . therefore, concerns remain about bridging patients with ecmo to lung transplantation. however, most data on lung transplantation after bridging with ecmo is drawn from retrospective, single-institution studies, and data describing long-term outcomes after lung transplantation are limited. the objective of this study was to evaluate the mortality and long-term post transplantation outcomes of patients undergoing lung transplantation after bridging with ecmo by comparing them with non-bridge-ecmo patients through an analysis of korean organ transplantation registry (kotry) data. kotry is a prospective, multicenter cohort registry that includes kidney, liver, pancreas, heart, and lung transplantations in korea [ ] . lung transplanted patients from institutions are enrolled in kotry. patients are enrolled at the time of transplantation and then followed-up accordingly. each participating institution inputs data through a web-based case report form according to a standardized protocol. between march and december , a total of patients received lung transplantation and were registered in the kotry database. written informed consent is obtained from each patient prior to transplantation. if patients are unable to provide consent due to disease severity, informed consent is obtained from a relative or legal representative. this kotry study was reviewed and approved by the institutional ethics committees of each participating organization. the clinical data of patients received lung transplantation during study period were followed up until june . the entire cohort was divided into two groups: the control group (n = ) comprised recipients who did not require ecmo before lung transplantation and the bridge-ecmo group (n = ) comprised recipients who were bridged to lung transplantation with ecmo. post-transplant outcomes, including primary graft dysfunction (pgd) assessed and graded by the international society for heart and lung transplantation lung transplant injury grades [ ] , functional status at discharge, graft function, and survival up to months after lung transplantation were assessed. information about transplant recipients, donors, transplant operations, and postoperative follow-up results were prospectively collected. data for recipients including general demographic information, primary diagnosis, and pre-transplantation status, and data for donors including general demographic information, cause of brain death, and smoking status, were collected. transplant surgery data including unilateral or bilateral lung transplantation, operation time, ischemic time, need for intraoperative hemodynamic support, and hemodynamic support type were collected. kotry also includes data about post-transplantation results including immediate complications, need for organ support, prevalence of primary graft dysfunction, serial pulmonary function, and outcomes such as the length of hospital stay, in-hospital and -month mortality, function status at discharge, and comorbidities. the most recent information for each patient was collected at , , , and months after discharge, and then annually. the follow-up data were collected from patients by the attending physician and stored using the web-based case report form. all data are presented as medians and interquartile ranges for continuous variables, and as numbers and percentages for categorical variables. we compared the clinical characteristics and outcomes of the two groups using the mann-whitney u test or student's t-test, as appropriate, for continuous variables and the chi-square test or fisher's exact test for categorical variables. probability of survival curves for each group were estimated by the kaplan-meier method and compared by the logrank test. data were analyzed using ibm spss statistics for windows, version . (armonk, ny, usa). during the study period, a total of patients underwent lung transplantation and were registered in kotry. the baseline characteristics of the patients are shown in table . among them, ( . %) were male and the median age of all patients was . (interquartile range, iqr . - . ) years. idiopathic pulmonary fibrosis ( . %) was the most common reason for lung transplantation, followed by connective tissue disease associated interstitial lung disease ( . %) and bronchiolitis obliterans after hematopoietic stem cell transplantation ( . %). one patient received simultaneous heart-lung transplantation due to eisenmenger syndrome. all patients were receiving their first lung transplants. the pretransplant oxygenation with partial pressure of arterial oxygen (pao )/fraction of inspired oxygen (fio ) ratio (pao /fio ratio) was . (iqr . - . ). thirty-nine patients ( . %) received mv before lung transplantation and all patients in the bridge-ecmo group received mv simultaneously before lung transplantation. the median duration of bridging with ecmo was . (iqr . - . ) days in the bridge-ecmo group. veno-venous mode (n = , %) was the most common type of ecmo used in ecmo-bridge group, followed by veno-venousarterial in two and veno-arterial in one. all but four of cannulation configurations for veno-venous ecmo was femoro-femoral cannulation. the median age of donors was . (iqr . - . ) years and the most common cause of brain death was trauma ( . %). forty-six ( . %) donors were current smokers. all organs were from deceased donors. the intra-operation characteristics of the enrolled patients are shown in table the hospital mortality for all patients was . %, with no significant difference between the two groups ( . % in bridge-ecmo group and . % in non-bridge-ecmo group, p = . ). partially dependent ( . %) was the most common functional status at discharge, followed by fully independent ( . %), and was not different between the two groups. the majority of patients ( . % of bridge-ecmo group and . % of nonbridge-ecmo group) were discharged to their homes. only patients ( . %) required tracheostomy at discharge. as shown in table , the prevalence of pgd was not significantly different between the bridge-ecmo group and non-bridge-ecmo group at h, h, h, and h after lung transplantation (p = . , p = . , p = . , and p = . respectively). survival rate at months after lung transplantation was . %, and was not significantly different between the bridge-ecmo group ( . %) and non-bridge-ecmo group ( . %) (p = . ). bridging with ecmo prior to lung transplantation did not significantly affect overall survival (fig. ) . although the probability of survival for the bridge-ecmo group appeared to decrease in the first few months post-transplantation, this difference was not statistically significant (p = . , log-rank test). in addition, there were no significant differences in posttransplant lung function between the two groups at months, months, months, months, or months postoperatively (fig. ). in this multicenter prospective observational study, we found that there were no significant differences in immediate postoperative complications, development and severity of pgd, functional status at discharge, longterm survival, or lung function in patients who received bridging with ecmo compared with the control group, despite longer operation time, longer icu stay, and longer hospitalization after lung transplantation in the former group. ecmo support improves outcomes in patients with life-threatening respiratory failure [ ] and the application of ecmo as a rescue therapy is expanding in clinical practice [ ] . in addition, ecmo has become a lifesaving intervention for a subset of rapidly deteriorating patients with end-stage lung disease, which offers optimizing gas exchange and end-organ perfusion to patients who might otherwise die before a suitable donor [ ] . in contrast, inci et al. showed worse overall and month conditional survivals in the bridge-ecmo group (n = ) versus the non-bridge-ecmo group (n = ) ( % versus %, p = . ; % versus %, p = . , respectively) [ ] . in the present study, the -month mortality of all patients was . % and there was no significant difference between the bridge-ecmo group and non-bridge-ecmo group in this respect ( . and . %, p = . ). the strength of our study is that recent, multi-institutional data for lung transplantation and a large sample of bridge-ecmo patients were included. these results indicate that bridging with ecmo is effective for patients awaiting lung transplantation due to the recent evolution of icu care and ecmo management. in this study, we also provide valuable information about short-term post transplantation outcomes. despite technical improvements, ecmo is associated with risks of complications including hemolysis and need for transfusion, cardiovascular dysfunction, bleeding due to anticoagulation, and thrombosis formation. furthermore, icu admission for ecmo management leads to icu-acquired weakness and infection associated with catheter or icu care [ , ] . our results indicate that post-operative bleeding ( . %) is the most common immediate co-morbidity evaluated at months after lung transplantation complication in bridge-ecmo patients, while infection ( . %) is the most common in the non-bridge-ecmo group, although there were no significant differences in number of immediate complications after transplantation including post-operative bleeding, infection, and airway complications between the two groups. all patients but two showed feasible functional status at discharge and all patients but one were discharged home in the bridge-ecmo group. these results indicate that bridging with ecmo is feasible for patients awaiting lung transplantation by considering not only survival but also quality of life after discharge. in the present study, the long-term outcomes of lung transplantation after bridging with ecmo were considered acceptable. kotry collects data for each patient serially at , , , months after discharge, and then annually. however, our analysis includes only years of follow-up data since the inclusion of lung transplant patients in kotry was initiated only in . pulmonary function, including predicted fev and fvc, showed no significant differences between the bridge-ecmo group and non-bridge-ecmo group at months, months, months, months, or months follow-up. comorbidities including hypertension, diabetes, and maintenance hemodialysis that developed within years after lung transplantation did not significantly differ between the two groups. these findings suggest that long-term prognosis for lung transplant patients after bridge ecmo is acceptable, if lung transplantation is successful. although the results of this study provide additional information on short-and long-term outcomes of lung transplantation after bridging with ecmo in a relatively large sample from a prospective multicenter registry, the study has several limitations that should be acknowledged. first, because of the observational ecmo extracorporeal membrane oxygenation, pgd primary graft dysfunction nature of the study, our findings remain prone to various biases. we used a national multicenter designed to improve the generalizability of our findings, but there is a potential risk of selection bias. in addition, differences in pre-transplantation status between the two groups should be considered, which might influence the clinical outcomes. although the bridge-ecmo group was more severely ill before transplantation, however, transplantation outcomes was comparable. second, because kotry was designed to collect the follow up data of lung transplantation, detailed information on the clinical status prior to ecmo, ecmo management including case selection, and rehabilitation prior to transplantation was not systematically collected. third, kotry includes a large number of bridge-ecmo patients compared to other studies [ ] [ ] [ ] . the high rate of bridge with ecmo in our study may reflect the korean lung allocation system based firstly on urgency of transplant [ ] , which is different from the european lung allocation score system based on the expected benefit after lung transplantation as well as the disease severity. under a medical urgency- in conclusion, lung transplantation after bridging with ecmo leads to acceptable patient outcomes. however, current evidence does not permit firm conclusions regarding the efficacy of bridging with ecmo and further systematic multicenter trials among carefully selected patients with end-stage lung disease are needed. lung transplantation lung transplantation current status and future of lung donation in korea organ donation and utilization in the united states intensive care unit management of patients with severe pulmonary hypertension and right heart failure ventilator-associated pneumonia in the icu adverse heart-lung interactions in ventilator-induced lung injury ventilator-induced lung injury should lung transplantation be performed for patients on mechanical respiratory support? the us experience the impact of pretransplant mechanical ventilation on short-and long-term survival after lung transplantation efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial bridge to lung transplantation with extracorporeal membrane oxygenation support outcomes of extracorporeal membrane oxygenation as a bridge to lung transplantation extracorporeal membrane oxygenation as a bridge to lung retransplantation: is there a role? outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation: an institutional experience and literature review extra corporeal membrane oxygenation (ecmo) review of a lifesaving technology extracorporeal life support as bridge to lung transplantation: a systematic review first report of the korean lung transplantation registry report of the ishlt working group on primary lung graft dysfunction part ii: definition. a consensus statement of the international society for heart and lung transplantation extracorporeal life support organization registry international report -year experience of prolonged extracorporeal membrane oxygenation in critically ill children with cardiac or pulmonary failure efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation spontaneously breathing extracorporeal membrane oxygenation support provides the optimal bridge to lung transplantation incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis icu-acquired weakness and recovery from critical illness extracorporeal membrane oxygenation as a bridge to lung transplantation in the united states: an evolving strategy in the management of rapidly advancing pulmonary disease bridge to lung transplantation and rescue post-transplant: the expanding role of extracorporeal membrane oxygenation characteristics of lung allocation and outcomes of lung transplant according to the korean urgency status publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. authors' contributions rek conceived and designed the study, analyzed the data and drafted this manuscript. jgl, syk, ytk, smc, dhk, whc, sip, kwj, hkk, and hcp contributed to the design of this study, analysis of the data, and revising of the manuscript. kj conceived and designed the study, analyzed the data, and wrote the final manuscript. all authors have read and approved the final manuscript. the data that support the findings of this study are available on request from the corresponding author. the data are not publicly available due to privacy or ethical restrictions. the institutional review boards of each participating organization approved this study. written informed consent is obtained from each patient prior to transplantation. the authors declare that they have no competing interests.author details key: cord- -gsy f y authors: nair, priya; davies, andrew r.; beca, john; bellomo, rinaldo; ellwood, david; forrest, paul; jackson, andrew; pye, roger; seppelt, ian; sullivan, elizabeth; webb, steve title: extracorporeal membrane oxygenation for severe ards in pregnant and postpartum women during the h n pandemic date: - - journal: intensive care med doi: . /s - - -z sha: doc_id: cord_uid: gsy f y purpose: to describe the technical challenges, efficacy, complications and maternal and infant outcomes associated with extracorporeal membrane oxygenation (ecmo) for severe adult respiratory distress syndrome (ards) in pregnant or postpartum patients during the h n pandemic. methods: twelve critically ill pregnant and postpartum women were included in this retrospective observational study on the application of ecmo for the treatment of severe ards refractory to standard treatment. the study was conducted at seven tertiary hospitals in australia and new zealand. results: of the patients treated with ecmo, ( %) were pregnant and ( %) were postpartum. their median (interquartile range [iqr]) age was ( – ) years, ( %) were obese. two patients were initially treated with veno-arterial (va) ecmo. all others received veno-venous (vv) ecmo with one or two drainage cannulae. ecmo circuit-related complications were rare, circuit change was needed in only two cases and there was no sudden circuit failure. on the other hand, bleeding was common, leading to relatively large volumes of packed red blood cell transfusion (median [iqr] volume transfused was , [ , – , ] ml) and was the main cause of death (three cases). eight ( %) patients survived to discharge and seven were ambulant, with normal oxygen saturations. the survival rate of infants whose mothers received ecmo was % and surviving infants were discharged home with no sequelae. conclusions: the use of ecmo for severe ards in pregnant and postpartum women was associated with a % survival rate. the most common cause of death was bleeding. infants delivered of mothers who had received ecmo had a % survival rate and, like their mothers, had no permanent sequelae at hospital discharge. electronic supplementary material: the online version of this article (doi: . /s - - -z) contains supplementary material, which is available to authorized users. extracorporeal membrane oxygenation (ecmo) for severe adult respiratory distress syndrome (ards) in pregnant or postpartum patients during the h n pandemic. methods: twelve critically ill pregnant and postpartum women were included in this retrospective observational study on the application of ecmo for the treatment of severe ards refractory to standard treatment. the study was conducted at seven tertiary hospitals in australia and new zealand. results: of the patients treated with ecmo, ( %) were pregnant and ( %) were postpartum. their median (interquartile range [iqr]) age was ( - ) years, ( %) were obese. two patients were initially treated with veno-arterial (va) ecmo. all others received venovenous (vv) ecmo with one or two drainage cannulae. ecmo circuitrelated complications were rare, circuit change was needed in only two cases and there was no sudden circuit failure. on the other hand, bleeding was common, leading to relatively large volumes of packed red blood cell transfusion (median [iqr] volume transfused was , [ , ] ml) and was the main cause of death (three cases). eight ( %) patients survived to discharge and seven were ambulant, with normal oxygen saturations. the survival rate of infants whose mothers introduction extracorporeal membrane oxygenation (ecmo) is a method for supporting patients with severe adult respiratory distress syndrome (ards) refractory to mechanical ventilation [ ] [ ] [ ] . ecmo has been used in neonates and children with satisfactory outcomes [ , ] . more recently, technical advances have enabled its safer application in adults [ , ] . among such adults, occasional patients have been supported with ecmo while pregnant or in the postpartum period. such treatments have led to individual case reports only [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . this lack of information makes it difficult to assess the safety and efficacy of this procedure in pregnant women and to estimate how it might affect maternal and/or infant outcome. in the winter of , patients were admitted to intensive care units (icus) in australia and new zealand with the pandemic swine-origin (h n ) influenza [ ] . ecmo was used in adult patients who had either h n influenza or strongly suspected h n influenza [ ] . of these, were pregnant or postpartum, which were described as part of the published cohort [ ] . two patients presented immediately subsequent and were added to aggregate to a series of , thereby providing the largest source of information to date on the safety and efficacy of ecmo during pregnancy. accordingly, we now report on the various technical aspects and challenges of ecmo therapy in this cohort of pregnant and postpartum women with severe respiratory failure and describe maternal and infant outcomes. data collection was approved by the relevant human research ethics committees. we collected information on all pregnant and postpartum women (within days of delivery) treated with ecmo for confirmed or strongly suspected h n influenza-associated respiratory failure during the winter period (june st through september th) in the icus that provided ecmo support in australia and new zealand. women who were postpartum at the time of ecmo commencement, but pregnant at the onset of influenza were included as they still had the anatomical, physiological and immunological alterations associated with pregnancy. please see the electronic supplementary material (esm) for details of data collection and statistical analysis. of the patients treated with ecmo, ( %) were pregnant and ( %) were postpartum. the median (iqr) age was ( - ) years. the associated comorbidities are summarized in table . a diagnosis of h n infection was confirmed in ( %) patients, had positive serology for influenza a and had clinical features highly suggestive of influenza during a pandemic. details regarding the severity of ards and the ecmo technical characteristics are described in the esm and table . the median (iqr) duration of mechanical ventilation was ( - ) days. seven ( %) patients required a tracheostomy to facilitate weaning from ventilation. all patients received packed red blood cell transfusion during ecmo therapy. the median (iqr) volume of blood transfused per patient during ecmo therapy was , ( , - , ) ml. five patients required platelet transfusions, of who also required fresh frozen plasma. all patients received vasoactive drug infusions at some time during ecmo therapy. the median (iqr) duration of ecmo support was ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days. the length of icu stay and hospital stay is reported in table . ten ( %) patients initially received vv ecmo and ( %) received va ecmo (table ) . va ecmo was the initial choice in the two patients due to the finding of moderate or severe left ventricular dysfunction on echocardiography. all patients had vascular cannulae inserted peripherally by a percutaneous seldinger technique. six ( %) patients received an additional venous drainage line ( drainage lines and return line) as blood flow rates through the circuit were deemed inadequate for effective therapy ( table ) . all circuits used a quadrox d oxygenator (maquet, rastatt, germany) and in ( %) patients, a jostra pump head (maquet, rastatt, germany). all patients received therapeutic anticoagulation ( table ). in ( %) patients, a single circuit was utilized for the duration of the entire treatment, whereas two patients required a circuit change due to progressive failure of the initial circuit. blood flow through the ecmo circuit at and h is reported in table . eight ( %) patients were successfully weaned from ecmo, all of who survived to hospital discharge (table ) . of these, ( %) were discharged home and patient was discharged to a rehabilitation facility. all eight patients were ambulant at discharge with a median room air oxygen saturation of % ( - ). six of the eight survivors were assessed for quality of life between and months after hospital discharge using the short form (sf v Ò ) tool. their summary scores in both the physical health and mental health components were found to be similar to the australian norms for an ageand sex-matched population. two non-survivors were pregnant and two were postpartum. of the four non-survivors, two died of bleeding (other than intracranial; one pulmonary and one from multiple sites), one died from intracranial haemorrhage and one of overwhelming fungal infection. details of bleeding complications are included in table . table shows comparative outcomes between this cohort of patients and the non-pregnant cohort of women of childbearing age ( - years) who received ecmo support during the same time period. eight ( %) patients suffered from bleeding complications (requiring transfusion) during ecmo support (table ). seven ( %) patients acquired one or more nosocomial infection. of the infections encountered, one was bloodstream, four were respiratory, one was urinary tract, one was line-related and five were wound infections. one maternal death was attributed to infection. other significant complications noted were limb ischaemia in two cases in patients receiving va ecmo (neither of which required amputation or embolectomy), and venous thromboembolism ( ) . no technical difficulties, such as accidental decannulation, disconnection, oxygenator failure, pump failure, haemolysis, air embolism or other circuit complications, were noted in this cohort of patients. there were no thrombotic complications. three patients ( %) were primigravida. the median (iqr) gestational age at the time of icu admission for the seven pregnant patients was ( - ) weeks. none of the pregnant patients were in the first trimester of pregnancy. of the five postpartum patients, all received ecmo therapy within a week of delivery. three of the pregnancies ( %) were complicated by pre-eclampsia and one patient had a placenta praevia. there were no multiple pregnancies. three patients ( %) had a preterm operative delivery due to the severity of the maternal illness. of the patients, delivered spontaneously, had vacuum-assisted delivery and had caesarean sections ( patients after ecmo therapy was completed, just after ecmo was commenced due to extreme severity of maternal illness and prior to the commencement of ecmo therapy). five of the ( %) infants delivered after commencement of ecmo were live births (table ) . of the two stillborn infants, pregnancy was terminated due to the severity of maternal illness in one case and in the second, there was a spontaneous birth of a stillborn infant shortly after commencing ecmo treatment. the median gestational age at birth was ( - ) weeks. the median birth weight was , ( - , ) g. two of the liveborn infants had a low apgar score (between and ) min after birth. four of live-born infants were admitted to a special care unit for respiratory support. no congenital abnormalities were noted. all the live-born infants survived. we studied the technical challenges, efficacy, complications and maternal and infant outcomes in a cohort of critically ill pregnant and postpartum patients with severe, hypoxic respiratory failure secondary to ards during the h n pandemic who were treated with ecmo. we found that obesity (pre-pregnancy bmi [ ) was common and that, despite significant right ventricular dysfunction in four patients, only two were initially treated with va ecmo and that adequate gas exchange was achieved in all cases. circuit-related complications were rare; circuit change was needed in only two cases and there was no sudden circuit failure. on the other hand, bleeding was common and responsible for the transfusion of large volumes of packed red blood cells and significantly contributed to three of the four deaths. eight ( %) patients survived and seven were ambulant and comparison with previous studies publications regarding the use of ecmo in pregnancy have, so far, only been single case reports. of the five patients described with respiratory failure [ ] [ ] [ ] [ ] [ ] , four survived and of the five infants, three survived. in the recent cesar study [ ] , a multi-centre randomized control trial comparing transfer to an ecmo centre for ecmo therapy to conventional mechanical ventilation alone in severe ards (but not pregnant patients), the survival rate for ecmo therapy was % overall. the australian and new zealand observational study [ ] of adult patients treated with ecmo for severe respiratory failure during the winter of (of which some the patients reported in this study are a subset) reported an overall survival of % ( % ci - %) [ ] . our study suggests that ecmo is an appropriate life supportive option in pregnant and postpartum patients with severe respiratory failure and extreme levels of hypoxia, and that when utilized in this setting, it can deliver acceptable maternal and infant outcomes. such outcomes may be related to the very early use of ecmo, thereby limiting the duration of maternal hypoxia, hypercarbia and acidosis as well as limiting the duration of ventilator-associated lung injury. bleeding was the most common complication of therapy and it was the major contributing factor in three deaths. this finding, the concurrent observations that no patient experienced thrombotic complications, that only two circuits required change and that none failed suddenly all indicate that these patients were likely relatively over-anticoagulated during ecmo. this may suggest the need for a conservative approach to anticoagulation during ecmo treatment in pregnant women. also, of clinical relevance is the observation that the presence of right ventricular dysfunction does not necessarily require va ecmo support and that once mechanical ventilation is minimized and the right heart decompressed, the systemic circulation remains stable. our study is a retrospective case series, with the associated inherent shortcomings, including the lack of randomization of treatment to ecmo or standard care. patient selection for ecmo and subsequent management of these challenging cases was determined by clinicians based on experience, limited current literature and local guidelines. however, equipment, policies and practices remained relatively homogenous owing to integrated intensive care services and training in our two countries. our study does not report on the long-term pulmonary function tests of the mothers or the long-term neurological sequelae in the infants. consequently, these results may not be generalisable to pregnant and postpartum patients who receive ecmo for other conditions. to our knowledge, however, this is the largest published series of pregnant and/or postpartum patients treated with ecmo. it includes the complete experience from our two countries during the pandemic. the propensity of the h n virus to cause severe respiratory failure in young adults with an increased risk in pregnant and postpartum women [ , ] enabled us to study a number of patients with similar lung pathology over a relatively short time span. the findings of our study have relevance to the treatment of future patients who may present with severe h n ards in subsequent outbreaks. ecmo support for severe respiratory failure is technically feasible in pregnant and postpartum patients-femoral vascular cannulation and prolonged circuit life are possible and adequate oxygenation is achievable despite the recognised augmented cardiac output. ecmo is effective, with outcomes comparable to those of non-pregnant patients, and acceptable infant outcomes. although ecmo was relatively safe, with complication rates similar to other groups, major bleeding contributed to significant morbidity and mortality suggesting that a low anticoagulation or anticoagulation-free approach in future patients may be prudent. extracorporeal membrane oxygenation for adult respiratory failure extracorporeal life support for severe acute respiratory distress syndrome in adults extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database impact of ecmo on neonatal mortality in michigan ( - ) extracorporeal membrane oxygenation for the treatment of neonatal respiratory failure efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation in pregnancy prolonged extracorporeal life support (ecls) for varicella pneumonia staphylococcal septicaemia and adult respiratory distress syndrome in pregnancy treated with extracorporeal carbon dioxide removal chicken-pox pneumonia, its complications and management. a report of three cases, including the use of extracorporeal membrane oxygenation extracorporeal membrane oxygenation in pregnancy extracorporeal membrane oxygenation for ards due to influenza a (h n )-reply (letter to editor) extracorporeal membrane oxygenation for circulatory arrest due to postpartum haemorrhage a potentially preventable case of severe influenza infection in a pregnant patient severe transfusionrelated acute lung injury managed with extracorporeal membrane oxygenation (ecmo) in an obstetric patient critical care services and h n influenza in australia and new zealand extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome anzic influenza investigators pandemic (h n ) influenza (''swine flu'') in australian and new zealand intensive care prone positioning of influenza h n patients with acute respiratory distress syndrome we also thank all the physicians, nurses and perfusionists who cared for these complex patients.conflict of interest none reported. key: cord- - fxpn qf authors: cantwell, tamara; ferre, andrés; van sint jan, nicolette; blamey, rodrigo; dreyse, jorge; baeza, cristian; diaz, rodrigo; regueira, tomás title: leptospirosis-associated catastrophic respiratory failure supported by extracorporeal membrane oxygenation date: - - journal: j artif organs doi: . /s - - -x sha: doc_id: cord_uid: fxpn qf a previously healthy, -year-old obese farmer, arrived hypotensive and tachycardic, with fever, myalgia, headache, abdominal pain, diarrhea, and progressive dyspnea. ten days before symptoms onset, he was in direct contact with mice and working in a contaminated drain. patient laboratory showed acute kidney injury and thrombocytopenia. chest x-ray exhibited bilateral diffuse interstitial infiltrates. first-line empirical antibiotics were started and influenza discarded. patient evolved with severe respiratory failure, associated with hemoptysis, and rapidly severe hemodynamic compromise. despite neuromuscular blockade and prone positioning, respiratory failure increased. accordingly, veno-venous ecmo was initiated, with bilateral femoral extraction and jugular return. after ecmo connection, there was no significant improvement in oxygenation, and low pre-membrane saturations and low arterial pao( ) of the membrane showed that we were out of the limits of the rated flow. thus, a second membrane oxygenator was installed in parallel. afterward, oxygenation improved, with subsequent perfusion enhancement. regarding etiology, due to high suspicion index, leptospira serology was performed, coming back positive and meropenem was maintained. the patient ultimately recovered and experience excellent outcome. the clinical relevance of the case is the scared evidence of leptospirosis-associated severe respiratory failure treated with ecmo. this experience emphasizes the importance of an optimal support, which requires enough membrane surface and flow for an obese, highly hyperdynamic patient, during this reversible disease. a high index of suspicion is needed for an adequate diagnosis of leptospirosis to implement the correct treatment, particularly in the association of respiratory failure, pulmonary hemorrhage, and an epidemiological-related context. leptospirosis is a zoonosis caused by pathogenic spirochetes of the genus leptospira that typically occurs in tropical and temperate regions. the global incidence is not well established, but the world health organization estimates that there are , cases per year in the world, causing with , deaths [ ] . although its incidence rate is increasing, with multiple outbreaks and significant morbidity, it remains an elusive diagnosis [ ] . it is under national surveillance in chile since , but the scarce number of cases per year is probably explained because of underdiagnoses. leptospira infects both wild and domestic mammalsrodents, cows, and dogs, among others, but rodents are the most important vectors [ ] . infection is acquired via direct patient skin or mucosa contact with infected animals; or indirectly, through contact with contaminated urine (environmental contamination, particularly in stagnant water) [ ] . exposure is common among farmers and septic drain clean up crews. symptoms usually begin or weeks after infection, and are characterized by fever accompanied by a broad abstract a previously healthy, -year-old obese farmer, arrived hypotensive and tachycardic, with fever, myalgia, headache, abdominal pain, diarrhea, and progressive dyspnea. ten days before symptoms onset, he was in direct contact with mice and working in a contaminated drain. patient laboratory showed acute kidney injury and thrombocytopenia. chest x-ray exhibited bilateral diffuse interstitial infiltrates. first-line empirical antibiotics were started and influenza discarded. patient evolved with severe respiratory failure, associated with hemoptysis, and rapidly severe hemodynamic compromise. despite neuromuscular blockade and prone positioning, respiratory failure increased. accordingly, veno-venous ecmo was initiated, with bilateral femoral extraction and jugular return. after ecmo connection, there was no significant improvement in oxygenation, and low pre-membrane saturations and low arterial pao of the membrane showed that we were out of the limits of the rated flow. thus, a second membrane oxygenator was installed in parallel. afterward, oxygenation improved, with subsequent perfusion enhancement. regarding etiology, due to high suspicion index, leptospira serology was performed, coming back positive and meropenem was maintained. the patient ultimately recovered and experience excellent outcome. the clinical relevance of the case is the scared a high index of suspicion is required for diagnosis, based mainly in epidemiological data of exposure and the previously described symptoms. since clinical and laboratory findings are non-specific, serological test is needed for diagnostic confirmation. culture and molecular diagnosis are available in some reference laboratories only. previously healthy, -year-old ( kg and cm) obese farmer, arrived at the emergency department (ed) with fever, retro-orbital headache, and intense muscular pain. on interrogation, days before symptom onset, he was in direct contact with mice and working in a contaminated drain. after initial evaluation, he receives symptomatic treatment and was discharged. he evolved with abdominal pain, vomiting, diarrhea and dyspnea, reason why he consults at the ed h later. on admission, he was hypotensive, tachycardic, non-febrile, with % pulse oximetry saturation breathing room air. chest x-ray showed bilateral diffuse interstitial infiltrates. initial laboratory findings are presented in table . due to local chilean epidemiology, rapid test for hantavirus and influenza a and b were performed, which where negative for these pathogens. with presumptive diagnosis of multiorgan dysfunction due to septic shock secondary to interstitial pneumonia, he was admitted the icu. first-line empirical antibiotics were started (ceftriaxone and metronidazole). during the following hours, severe dyspnea, with progressive oxygen requirement and hemoptysis ensued. he was intubated, sedated, and protective invasive mechanical ventilation initiated. rapidly severe hemodynamic compromise presented (noradrenaline requirement up to . mcg/kg/min and adrenaline up to . mcg/kg/min). in addition, oxygenation parameters dropped to a pao :fio ratio (pa/fio ) of ; leading to neuromuscular blockade initiation and peep adjustments. control laboratory parameters are shown in table . at this point, due to progressive respiratory failure, transferred was requested to a center with ecmo availability, thus being transferred to our hospital. upon admission, the patient exhibited severe hemodynamic instability with high vasoactive drug requirements, catastrophic respiratory failure, with a pa/fio ratio of , and oliguric renal failure. calculated apache ii score was . initial bedside echocardiography was suggestive of hypovolemia, with no right cavities dilatation and good left ventricle contractility. pulmonary imaging showed diffuse bilateral opacities (fig. ) . preload was optimized, profound sedation and neuromuscular blockade were adjusted, and high-volume hemofiltration (hvhf) was initiated, with a good clinical response associated with a % reduction in vasoactive drugs. admission blood cultures, bronchial secretion, and urine cultures came back negative, but herpes simplex virus type i was detected on respiratory tract, interpreted as an epiphenomenon. hiv and repeated hantavirus serology were negative. due to profound septic shock and considering its catastrophic course, empirical second-line antibiotics were started (meropenem, vancomycin, amikacin, plus iv. acyclovir). an initial good respiratory and hemodynamic response was observed for h; however, after one episode of hemoptysis, abrupt deterioration in gas exchange, mainly oxygenation, ensued. prone maneuver was attempted, but pa/ fio ratio remained below with a murray score of . accordingly, veno-venous ecmo was initiated, with bilateral femoral extraction ( f and f) and jugular return ( f). a euroset polymethylpentene oxygenator was used. after ecmo connection, there was not a significant improvement in oxygenation, although all usual parameters were optimized. low pre-membrane saturations and low arterial pao of the membrane showed that we were out of the limits of the rated flow. thus, a second membrane oxygenator was installed (in parallel- fig. ) . afterward, oxygenation improved, with subsequent perfusion enhancement, evidenced by a positive lactate clearance. a second bedside echocardiography showed a drop in left ventricular ejection fraction, but without pulmonary hypertension, and it was interpreted as septic/hypoxic cardiomyopathy. on the following days, several transfusions were required due to anemia and thrombocytopenia, and numerous bronchoscopies were also necessary for airway clots toilette. alteration on hepatic laboratory values was initially interpreted as septic shock hepatitis. regarding etiology, due to high suspicion index, leptospira serology was performed, coming back positive; thus, meropenem was maintained. acyclovir therapy was administered for days. during his evolution, a tracheobronchitis due to resistant klebsiella oxytoca was treated, and an important epistaxis required posterior tamponade for days, both pathologies resolved without further complications. uveitis was discarded by ophthalmologic evaluation. initially, high ecmo flows were necessary, up to l with oxygenators, without evidence of mechanical complications. progressive improvement in pulmonary function and images (fig. ) allowed for ecmo withdrawal on day . afterward, pseudoaneurism of the right femoral artery, which was not cannulated, became evident, and was surgically repaired without complications. the patient was discharged home on day , completely recovered and with no sequalae. leptospirosis can present with a wide range of symptoms, mimicking flu, hepatitis, dengue, hanta virus cardiopulmonary syndrome, meningitis, among others, and has a specific treatment; thus, clinical suspicion must remain high and serological diagnosis should be performed. in chile, hanta virus [ ] and influenza are the most common differential diagnosis of patients presenting with flu-like symptoms and respiratory failure in the right epidemiological setting. fig. chest x-ray and ct evolution of the patients a before and b after ecmo classic manifestations of leptospirosis are mainly due to its pathogenic mechanism, in which a bacterial glycoprotein acts as endotoxin and perforates cell membranes [ ] . later, via hematogenous dissemination, small blood vessel vasculitis can develop [ , ] . due to its multi-systemic involvement, severe disease can exhibit a wide variety of signs and symptoms. among these, our patient presented with hepatitis, acute kidney injury, acute respiratory distress syndrome (ards), pulmonary hemorrhage, which is present in up to . % of cases [ ] , myocarditis, and rhabdomyolysis. the most severe clinical form of leptospirosis is known as weil's disease, which is uncommon ( - % of cases), and is characterized by hepatic, renal, and pulmonary involvement [ ] [ ] [ ] [ ] [ ] . other possible complications, not presented in our patient, include lymphocytic meningitis, and uveitis [ ] [ ] [ ] . characteristic associated vasculitis of the severe form of the disease can be extremely severe, in some cases leading to limb necrosis [ ] . acute kidney injury is due to tubular-interstitial nephritis and is often non-oliguric, and only sometimes requires renal replacement therapy. among survivors, renal function commonly recovers [ ] [ ] [ ] . in the presented case, intermittent high-volume hemofiltration was used in the setting of profound shock to decrease vasoplegia intensity. leptospirosis mortality rates in hospitalized patients range from to % [ ] . pulmonary and central nervous system involvement are described as predictors of mortality. in the case of pulmonary involvement, mortality rises to % [ ] . other series also suggest that jaundice, renal failure, and an age above are mortality risk factors [ , ] . in one series of cases, % of the patients present with specific organ involvement, with the other % of cases presenting with only a non-specific febrile syndrome [ , ] . many antibiotics are effectives for leptospirosis, including penicillin, rd generation cephalosporins, carbapenems, macrolides, and tetracyclines. in severe presentations, supportive therapies are essentials for survival, considering that multiorgan failure (mof) is typically completely reversible [ ] . veno-venous ecmo provides immediate support of oxygenation and ventilation and helps ensure protective ventilation without further compromising oxygen delivery nor acid base balance [ ] . in the case presented, profound septic shock, with mof and catastrophic ards, made it impossible to ventilate the patient protectively and simultaneously supply adequate oxygenation and ventilation; thus, ecmo was initiated. ecmo is increasingly being used for this type of patients with severe ards, but it is important to understand ecmo physiology, in particularly in obese and hyperdynamic patients, such as the presented case [ ] . this obese patient, with a body surface area of . - . m and an estimate required cardiac index of at least l/min/m , needs approximately to l min of oxygenated cardiac output. initially, with only one oxygenator, ecmo flow was . l min, with a fully oxygenated blood (pao after oxygenator of mmhg); accordingly, even with no recirculation, this table patient arterial and post oxygenator's blood gas evolution paco carbon dioxide partial pressure in patient's arterial blood gas (mmhg), pao oxygen partial pressure in patient's arterial blood gas (mmhg), ecmo negative pressure: circuit pressure before pump (mmhg), day * h post-second oxygenator; ox / pco carbon dioxide partial pressure in post oxygenator's blood gas (mmhg), ox / po oxygen partial pressure in post oxygenator's blood gas (mmhg) flow was insufficient to meet patient requirements. the addition of a second oxygenator allow us to increase oxygenated blood flow to l/min, increasing oxygen delivery, and better meet patient oxygen demands (table ). in parallel we try to decrease oxygen consumption by decreasing the patient hyperdynamic state with high flow hemofiltration and temperature management. the need of double oxygenators in veno-venous ecmo is not frequently reported [ ] , but it could be highly useful as a strategy to reach adequate oxygen delivery (do ) to surpass the patient vo , thus stopping the oxygen debt and the shock vicious cycle. to our knowledge, this is one of the few cases that describes the need of ecmo in weil disease, and in addition, with a good outcome [ , ] . all cases have in common the presence of pulmonary hemorrhage as a cause of pulmonary insufficiency, as is our case. a high index of suspicious, combined with the appropriated supportive therapy, was essential for patient survival. world health organization. global burden of human leptospirosis and cross-sectoral interventions for its prevention and control emergence, control and re-emerging leptospirosis: dynamics of infection in the changing world leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen leptospirosis: an emerging disease in travellers cardio-pulmonary manifestations of hantavirus pulmonary syndrome leptospirosis in latin america anicteric leptospirosis-associated severe pulmonary hemorrhagic syndrome: a case series study epidemic leptospirosis associated with pulmonary hemorrhage-nicaragua role of nonesterified unsaturated fatty acids in the pathophysiological processes of leptospiral infection leptospirosis renal disease identification of leptospira species in the pathogenesis of uveitis and determination of clinical ocular characteristics in south india leptospirosis: análisis de casos - uveitis associated with an epidemic outbreak of leptospirosis leptospirosis: a childhood disease acute renal failure: a common manifestation of leptospirosis acute kidney injury requiring hemodialysis in patients with anicteric leptospirosis pattern of renal function recovery after leptospirosis acute renal failure leptospirosis: prognostic factors associated with mortality clinical spectrum of pulmonary involvement in leptospirosis in a region of endemicity, with quantification of leptospiral burden epidemic of leptospirosis: an icu experience risk factors for mortality in patients with leptospirosis during an epidemic in northern kerala leptospirosis during dengue outbreak a systematic review of the mortality from untreated leptospirosis soporte cardio respiratorio avanzado rescue therapies for acute hypoxemic respiratory failure use two oxygenators during extracorporeal membrane oxygenator for a patient with acute respiratory distress síndrome, high-pressure ventilation, hipercapnia, and traumatic brain injury veno-arterial extracorporeal membrane oxygenation in acute respiratory distress syndome caused by leptospiresepsis leptospirosis: a case report os a petient with pulmonay haemorrhage successfully managed with extracorporeal membrane oxygenation key: cord- - q xdv authors: jacquet, l. -m. title: conduite et complications de l’oxygénation extracorporelle veinoveineuse date: - - journal: reanimation doi: . /s - - - sha: doc_id: cord_uid: q xdv this article reviews the management of patients treated with venovenous extracorporeal membrane oxygenation (ecmo) for acute respiratory failure refractory to the conventional therapies. the period of extracorporeal respiratory support can be divided in three successive periods: the period of ecmo initiation, the period of treatment with ecmo, and the period of ecmo weaning. we will describe the main technical aspects of ecmo as well as the monitoring of the extracorporeal circuit and the ecmo-treated patient. the most frequent complications in each period of the management of ecmo-treated patients will be described and the possible adequate solutions will be considered. le traitement de l'insuffisance respiratoire du syndrome de détresse respiratoire aiguë (sdra) par échanges gazeux extracorporels fait le plus souvent appel à une technique veinoveineuse d'oxygénation extracorporelle par membrane (ecmo vv). comme décrit antérieurement, plusieurs for mes de canulation sont possibles, le drainage par une longue canule en veine fémorale avec retour par une plus courte canule en veine jugulaire étant la technique la plus fréquem ment utilisée chez l'adulte. l'utilisation d'une canule uni que à double lumière placée en veine jugulaire interne sous contrôle radioscopique ou échocardiographique est, cepen dant, en augmentation constante depuis [ ] . au début du traitement, le débit du circuit est réglé pour être le plus proche possible du débit cardiaque du patient. en effet, le sang qui arrive dans l'artère pulmonaire est un mélange du sang qui a traversé le circuit extracorporel et du sang veineux désaturé qui n'a pas circulé en dehors de l'orga nisme. considérant la gravité habituelle de l'atteinte pulmonaire et la volonté de réduire au maximum l'agres sivité de la ventilation mécanique, la contribution des pou mons à l'oxygénation sanguine est généralement très faible, et la saturation artérielle systémique est fort proche de la saturation dans l'artère pulmonaire. l'oxygénation du sang du circuit externe dépend essentiellement de la fraction d'oxygène dans le gaz délivré à l'oxygénateur membra naire (f d o ) qui sera de au départ permettant de saturer l'hémoglobine à % (pour autant que le débit sanguin à travers l'oxygénateur soit inférieur au débit nominal de l'oxygénateur choisi). la saturation en oxygène du sang de l'artère pulmonaire sera dès lors fonction du rapport entre le débit du circuit, dont l'hémoglobine est saturée à %, et le débit veineux résiduel, dont la saturation devrait être de l'ordre de %. comme le débit cardiaque est la somme de ces deux débits, plus le rapport entre le débit du circuit et le débit cardiaque sera élevé, plus la saturation dans l'artère pulmonaire et la saturation artérielle systémique seront hau tes. il est dès lors primordial de pouvoir délivrer un débit extracorporel proche du débit cardiaque du patient en choi sissant une vitesse de rotation de la pompe adéquate. la plupart des pompes utilisées pour le support extra corporel de patients adultes étant des pompes centrifuges, il faudra toutefois éviter des vitesses de rotation trop éle vées qui peuvent engendrer des pressions d'aspiration trop négatives et/ou d'éjection trop élevées. lorsque la ligne de drainage est occluse, la pression d'aspiration ne devrait pas descendre en dessous de - mmhg [ ] . À ce niveau de pression, qui peut survenir en cas de succion (l'aspiration trop importante par rapport au retour veineux se manifes tant par des tremblements de la ligne de drainage), des phénomènes de cavitation peuvent s'observer. sous l'effet de la dépression, les gaz dissous peuvent passer en phase gazeuse, et l'interface gaz/sang ainsi créée est un puissant agent inducteur d'hémolyse [ ] . des pressions d'éjection élevées, audelà de mmhg, peuvent également être responsables d'épisodes hémolytiques suite aux forces de cisaillement élevées ainsi crées, sans compter le risque de rupture des lignes ou des connexions que de telles pres sions font courir. rappelons ici qu'un débitmètre doit être placé et calibré sur le circuit pour en mesurer le débit exact qui ne peut être estimé à partir de la vitesse de rotation. les saturations artérielles visées en début de traitement seront donc relativement faibles. les recommandations de l'extracorporeal life support organization (elso) sont de tendre vers une saturation artérielle de % et une satu ration veineuse de % [ ] . la plupart des équipes visent une saturation artérielle supérieure à %, mais il est vrai que dans des situations de haut débit cardiaque qu'on peut rencontrer dans les états septiques ou toxiques, il faut par fois se contenter de saturations bien inférieures. lorsqu'il n'est pas possible d'atteindre une oxygénation acceptable, il est parfois nécessaire d'ajouter une canule de drainage supplémentaire pour pouvoir augmenter le débit extérieur. un élément important dans l'évaluation du débit et de l'efficience du circuit est de tenir compte de la recirculation, c'estàdire de la quantité de sang oxygéné et décarboxylé envoyé par la canule de réinjection qui est immédiatement réaspiré par la canule de drainage et qui ne circule donc pas dans l'organisme. la quantité de sang qui recircule doit être soustraite du débit du circuit pour quantifier le débit réel lement efficace [ ] . il sera donc recommandé de contrôler rapidement par radiographie le positionnement correct des deux canules et la distance entre les deux extrémités. la recirculation peut être calculée en comparant la satura tion du sang veineux, prélevé, par exemple, par une voie centrale en amont de la canule de retour, avec la saturation du sang dans la branche de drainage du circuit. l'utilisation d'une seule canule à double lumière drainant le sang dans les deux veines caves pour le réinjecter en face de l'orifice de la valve tricuspide est, à ce point de vue, particulièrement intéressante même si la mise en place est un peu plus com plexe [ , ] . l'élimination du co est beaucoup moins dépendante du débit du circuit, tant l'efficacité des oxygénateurs membra naires est élevée pour l'extraction de ce gaz. avec des débits sanguins de à l/min, il est possible d'éliminer pratique ment la totalité du co produit par minute. la quantité de co éliminée est déterminée par le débit de gaz frais qui entre dans l'oxygénateur (communément appelé balayage) qui est réglé au niveau du mélangeur de gaz. au départ, puisque le débit sanguin dans le circuit est élevé pour main tenir l'oxygénation, il est recommandé de choisir un flux de balayage égal au débit sanguin extracorporel puis d'adapter le balayage en fonction de la paco . en cas d'hypercapnie préexistante, la correction peut être très rapide, mais il est prudent de viser une correction progressive pour éviter le développement d'une alcalose et de modifications de la per fusion cérébrale [ ] . c'est en profitant de la haute efficacité des membranes à éliminer le co que se sont développées des techniques d'épuration du dioxyde de carbone artérioveineuse ou veino veineuse à bas débit. nous y reviendrons plus loin. pour surveiller l'efficacité de l'oxygénateur membra naire, il sera nécessaire de faire des prélèvements sanguins chez le patient ainsi que sur les branches de drainage et de réinjection du circuit. il est possible sur certains circuits de suivre en continu les saturations avant et après la membrane par oxymétrie de transmission. de cette façon, l'adéquation du transport d'oxygène par rapport aux besoins, reflétée par la saturation veineuse, peut être monitorisée en permanence de même que l'efficience de l'oxygénateur. le nombre de prélèvements pourra dès lors être réduit. la paco sera sui vie sur les prélèvements artériels du patient et ne devra être vérifiée sur le circuit qu'en cas de modification inexpliquée. lors des prélèvements sur le circuit, principalement sur la branche de drainage, une prudence extrême est requise pour éviter toute entrée d'air dans le circuit qui pourrait avoir des conséquences désastreuses. toujours au niveau du circuit, on s'assurera de la connexion correcte et du réglage adéquat de l'échangeur thermique. une proportion significative du sang circule en dehors de l'organisme, et des dérèglements thermiques rapides sont possibles si, par exemple, le circulateur entre l'échangeur thermique et l'oxygénateur ne fonctionne pas correctement. les principaux éléments du circuit à sur veiller ainsi que les complications rencontrées avec ces composants sont repris dans la tableau . la conduite de la ventilation doit principalement per mettre de limiter au maximum les effets secondaires de la ventilation mécanique. quel que soit le mode de ventilation choisi, il faudra limiter la pression inspiratoire maximale à cmh o, le volume courant à ml/kg de poids idéal en maintenant une pression positive de fin d'expiration à - cmh o. la fréquence respiratoire pourra être dimi nuée à moins de dix ventilations par minute, tandis que la f i o sera réduite progressivement en dessous de , . la question reste débattue de savoir si une ventilation encore moins agressive en utilisant des volumes inférieurs à ml/kg, par exemple, ou des fréquences respiratoires de quatre à six par minute devrait être recommandée pour pro mouvoir la guérison pulmonaire [ , ] . durant la mise en place du circuit, il est souvent néces saire de placer le patient sous sédation et de maintenir une sédation dans les heures qui suivent. parfois, il est même nécessaire d'ajouter une curarisation pour assurer l'adap tation du patient au respirateur, mais l'administration de curares n'est à envisager qu'en cas de désaturation artérielle sous %. la mise en contact du sang avec le matériel étranger du circuit nécessite la mise en route d'une anticoagulation systémique. une dose de charge d'héparine est administrée lors de la mise en place des canules, et une perfusion conti nue doit être poursuivie en visant un allongement du temps de coagulation du sang total à - secondes et/ou du temps de thromboplastine partiel activé à , - fois la limite supérieure de la normale. les doses d'héparine nécessaires varient grandement en fonction de l'état du patient (throm bopénie, insuffisance rénale, état hyper coagulable…), de sorte qu'une dose standard est impossible à déterminer. puisque l'héparine agit par l'intermédiaire de l'activa tion de l'antithrombineiii plasmatique, des dosages de cette molécule sont utiles. un déficit en antithrombineiii doit être suspecté si l'anticoagulation souhaitée n'est pas atteinte ou si des signes de coagulation du circuit appa raissent malgré de hautes doses d'héparine. il peut être utile d'administrer du plasma frais congelé, voire des concentrés d'antithrombineiii dans ces situations [ , ] . les circuits couverts soit d'héparine, soit d'autres agents chimiques (phosphorylcholine, poly méthoxyéthyl acrylate, etc.) semblent diminuer l'intensité des interactions sang/ biomatériaux, et ils permettent, si des saignements importants apparaissent, de diminuer, voire d'arrêter l'anti coagulation systémique avec des risques limités de formation de throm bus pour autant que le débit dans le circuit ne soit pas trop faible [ , ] . À moins d'avoir eu le temps de remplir le circuit avec du sang, il faut s'attendre à une chute significative de l'héma tocrite suite à l'hémodilution par le liquide de remplissage et, donc, à la nécessité de transfuser le patient. les recom mandations de l'elso sont de transfuser des globules rou ges pour maintenir un hématocrite normal. si la saturation artérielle est acceptable (> %) et que le débit cardiaque est normal, voire élevé, des taux d'hémoglobine inférieurs sont tolérables pour autant que le transport d'oxygène reste adéquat [ ] . puisque l'hémodynamique n'est que peu influencée par la mise en route du circuit externe, la prise en charge hémo dynamique suivra les directives généralement appliquées en réanimation. du fait de l'augmentation du volume sanguin circulant et de l'adsorption possible de certaines molécules pharmacologiques sur les polymères du circuit, il peut être nécessaire d'adapter les doses de certaines médications administrées pour en maintenir l'effet thérapeutique sou haité [ , ] . dès que l'état clinique le permet, la sédation sera dimi nuée, l'idéal étant d'avoir un patient réveillé mais légère ment sédaté pour éviter des mouvements intempestifs qui pourraient provoquer une mobilisation des canules et les complications qui ne manqueraient pas de se manifester. les efforts de toux importants et répétés peuvent parfois empêcher un drainage correct vers le circuit dont le débit ne peut alors plus être maintenu, ce qui nécessite parfois de garder une sédation plus profonde que souhaité. différents modes de ventilation sont utilisés (ventilation contrôlée, pression positive continue des voies aériennes, ventilation avec relâchement de la pression des voies aériennes…). aucune étude n'a comparé les modes ventilatoires au cours de l'ecmo, et la seule recommandation qui peut être faite est de limiter les pressions, les volumes et la fraction inspi rée d'oxygène pour ne pas léser davantage les poumons. la saturation artérielle en oxygène de même que les saturations des branches de drainage et de réinjection du circuit continueront à être monitorisées pour s'assurer que les objectifs visés sont atteints et que l'oxygénateur mem branaire fonctionne correctement. des prélèvements pour analyse des gaz sanguins seront effectués au besoin, mais au minimum une fois par jour. une chute de pression partielle en oxygène à moins de mmhg après l'oxygénateur avec une fraction d'oxygène délivré égale à nécessite le rem placement de l'oxygénateur. les oxygénateurs récents sont conçus pour être utilisés plusieurs semaines, et il est devenu rarement nécessaire de changer l'oxygénateur sauf pour des supports de durée très prolongée ou en cas d'anticoagula tion nettement insuffisante. la perte d'efficience est, en effet, très souvent causée par l'obstruction des fibres par des caillots en formation. les paramètres de coagulation seront régulièrement évalués et particulièrement le temps de coagulation et/ou le temps de thromboplastine partiel activé pour ajuster les doses d'héparine. la numération des plaquettes san guines sera suivie de près, car une thrombopénie apparaît quasi systématiquement suite à l'activation des plaquettes au contact du matériel étranger. les plaquettes activées ont tendance à former des microaggrégats qui sont cap tés par le système réticuloendothélial du foie et de la rate. l'anticoagulation nécessaire associée à la consommation de plaquettes et de facteurs de coagulation dans le circuit expli quent la fréquence des complications hémorragiques ren contrées. récemment, la survenue d'un syndrome de von willebrand acquis a été mise en évidence dans une série de patients sur sous support extracorporel. les forces de cisaillement élevées dans la pompe pourraient favoriser le déplissement des multimères de haut poids moléculaire du facteur von willebrand et favoriser leur destruction par la protéine adamst . la disparition des multimères de haut poids moléculaire diminuerait les interactions entre les plaquettes et l'endothélium lésé, ce qui pourrait favo riser la survenue d'accidents hémorragiques [ ] . selon les définitions et les séries, l'incidence des hémorragies oscille entre et % des cas [ , , ] . elles peuvent survenir en de nombreuses localisations, mais les plus dévastatrices sont les saignements intracrâniens qui surviennent chez à % des patients et sont associés à une augmentation signi ficative de la mortalité [ , ] . les sites de canulation sont une source fréquente d'hémorragie avec des incidences rap portées entre et %. on relèvera également la survenue fréquente de saignements du tractus respiratoire supérieur ( à %) et du tube digestif ( à %). en cas de sai gnement significatif, l'anticoagulation peut être diminuée et même totalement arrêtée le temps de contrôler la situation. la diminution de l'anticoagulation sera plus sécure si le circuit est couvert d'héparine ou possède une surface trai tée. des globules rouges seront transfusés pour maintenir l'hématocrite proche de la normale. du plasma frais congelé sera administré en cas d'anomalie de l'hémostase (interna tional normalized ratio [inr] > , ), et du fibrinogène sera donné si la fibrinogénémie est inférieure à mg/dl. il faudra souvent transfuser des plaquettes pour maintenir leur taux à plus de /µl. même si le nombre de pla quettes n'est pas effondré, il existe souvent une thrombopa thie qui peut être mise en évidence par des tests de réactivité plaquettaire (multiplate…). des agents antifibrinolytiques (acide tranexamique, acide aminocaproïque) peuvent aider à contrôler un saignement surtout au niveau de sites chirur gicaux. le facteur vii recombinant activé a quelquefois été utilisé avec succès pour tarir un saignement grave, mais le risque thromboembolique n'est pas négligeable. l'utilisation d'héparine non fractionnée peut entraîner la synthèse d'anticorps dirigés contre le complexe héparinefacteur plaquettaire. ces anticorps se lient aux plaquettes entraînant leur activation et leur consommation (throm bopénie induite par l'héparine ou tih). une diminution soudaine du nombre de plaquettes doit pousser à réaliser les tests immunologiques et/ou fonctionnels plaquettaires pour confirmer le diagnostic. la survenue d'une tih, qui compliquerait à % des cas, nécessite l'arrêt de l'admi nistration d'héparine et l'utilisation d'autres anticoagulants (argatroban, lépirudine, bivalirudine…) [ , ] . des don nées contradictoires ont été publiées concernant l'utilisa tion de circuits couverts d'héparine dans ces circonstances, mais il nous paraît plus prudent d'éliminer également ces circuits qui pourraient entretenir la réaction immunolo gique [ , ] . des complications thrombotiques peuvent survenir suite à l'incapacité de moduler l'activation de la coagulation mal gré le traitement anticoagulant. l'apparition de caillots dans le circuit est rapportée dans % des cas et est favorisée par une anticoagulation insuffisante et/ou un bas débit dans le circuit. des caillots peuvent se former à tout endroit du circuit, mais ils apparaissent le plus souvent du côté veineux (en amont de l'oxygénateur membranaire), dans l'oxygéna teur ou dans la tête de pompe. le composant atteint doit être remplacé, et il est parfois nécessaire de remplacer tout le circuit. même s'ils ne sont pas visibles, les caillots dans le circuit entraînent fréquemment une hémolyse significative. le changement du circuit ou d'un de ses composants peut se faire rapidement lorsque le personnel est formé et entraîné. il faudra toutefois anticiper l'arrêt de la circulation externe et majorer le support ventilatoire avant de clamper les lignes du circuit. un double clampage est recommandé, un clamp étant placé près du patient sur chacune des lignes, et un deuxième clamp est fixé de part et d'autre du compo sant à changer. il faut bien sûr être très attentif et rigoureux pour éviter toute pénétration d'air dans le circuit, surtout du côté de la réinjection. des désordres plus profonds de la coagulation sont décrits chez - % des patients, en particulier, une coagula tion intravasculaire disséminée responsable d'une consom mation de tous les facteurs de coagulation, du fibrinogène et des plaquettes. une hémolyse éventuelle doit être recherchée active ment par le dosage de l'hémoglobine plasmatique qui est normalement inférieur à mg/dl. une élévation des lacti codéshydrogénases (ldh), de la bilirubine non conjuguée et des schizocytes de même que la coloration des urines sont également évocateurs d'une destruction trop impor tante des hématies. l'hémolyse peut être liée à des forces de cisaillement trop élevées si la pression d'aspiration est trop négative, ce qui peut se produire si l'aspiration de la pompe dépasse le retour veineux. si les pressions d'éjection sont trop élevées parce que la canule de réinjection offre une résistance trop importante (canule trop étroite pour le débit souhaité ou caillot en formation dans la canule), les forces de cisaillement créées peuvent aussi être responsa bles d'une hémolyse. très fréquemment, la destruction des globules rouges est due à la formation de caillots dans la tête de pompe et particulièrement au niveau de l'axe de support du rotor. ce risque est évidemment moindre pour les pom pes dépourvues d'axe mécanique dont le maintien du rotor est assuré par une suspension magnétique. même si la ventilation mécanique est maintenue à un niveau d'agression minimal, il n'est pas rare de voir appa raître des pneumothorax que l'on pourrait presque qualifier de spontanés. un pneumothorax de petite taille (< % du champ pulmonaire) ne doit pas nécessairement être drainé et peut se résorber spontanément. les pneumothorax de plus les complications infectieuses, bien que non spécifiques, sont particulièrement fréquentes. la publication austra lienne et néozélandaise sur l'utilisation de l'ecmo pen dant l'épidémie de grippe en rapporte une incidence de % d'infections [ ] . la plupart sont des infections ou des surinfections pulmonaires et des septicémies. une infec tion débutante n'est pas toujours facile à diagnostiquer chez le patient sous assistance extracorporelle du fait du contrôle de la température par l'échangeur thermique externe et des multiples causes possibles aux anomalies biologiques habi tuellement observées en cas d'infection (hyperleucocytose, thrombopénie, syndrome inflammatoire). en cas de septicé mie, un point d'entrée au niveau des canules doit être recher ché systématiquement, et les canules doivent être changées s'il y a une haute suspicion d'infection à ce niveau. l'insuffisance rénale est également fréquente et, généra lement, associée à un mauvais pronostic. l'incidence réelle est difficile à évaluer du fait de l'utilisation de critères dif férents selon les études mais, de façon assez constante, le recours à des thérapeutiques d'épuration extrarénale survient dans plus de % des cas [ , ] . la mortalité des patients traités par ecmo associée à une épuration extrarénale serait significativement plus élevée que celle des patients n'ayant pas nécessité une substitution de la fonction rénale [ ] . il est possible de tirer profit du circuit d'oxygénation extracorporelle pour y brancher un circuit d'ultrafiltration ou de dialyse. les principales complications et leurs incidences res pectives rapportées dans la littérature sont reprises dans la tableau . assez souvent, une trachéotomie est réalisée pour faci liter la levée de la sédation et envisager le sevrage de l'ecmo. la trachéotomie peut être percutanée ou chirurgi cale en fonction de l'anatomie du patient et de l'expérience des équipes. les investigateurs australiens et néozélandais rapportent la réalisation d'une trachéotomie chez % des patients traités par ecmo pour pneumonie à virus influenza h n [ ] . l'amélioration de la fonction pulmonaire apparaît assez simultanément sur les paramètres de la mécanique venti latoire (augmentation de la compliance pulmonaire), des échanges gazeux (meilleure oxygénation et rapport pao / fio ) et de la radiographie pulmonaire (éclaircissement des champs pulmonaires). quand ces signes apparaissent, il est possible de diminuer progressivement le débit de la circulation extracorporelle. si l'on suit la recommandation d'utiliser le débit le plus bas possible qui permet d'obtenir des valeurs de pao et p a co satisfaisantes, ce sevrage se fait assez automatiquement au fur et à mesure de la récu pération de la fonction pulmonaire. lorsque le débit atteint lorsque l'option thérapeutique est de diminuer au maxi mum l'agressivité de la ventilation mécanique sans recher cher à améliorer l'oxygénation, des techniques d'extraction du co par bas débit extracorporel ont été développées grâce à l'utilisation d'oxygénateurs membranaires offrant peu de résistance à l'écoulement sanguin et étant très effi caces pour l'élimination du co . la première technique consiste à utiliser un circuit externe d'assistance sans pompe (pumpless extracorporeal lung assist ou pecla) en créant un circuit artérioveineux et en utilisant le coeur du patient pour créer le débit et sa pression sanguine arté rielle comme pression de perfusion du circuit. il est, dès lors, indispensable que le patient génère un index car diaque minimal de l/min par m avec une pression arté rielle moyenne de mmhg. le flux dans le circuit dépend des paramètres hémodynamiques du patient, de la taille des canules artérielles de drainage et veineuse de retour ainsi que de la résistance de l'oxygénateur. avec une canule artérielle de - fr et une canule veineuse de - fr, des débits de l'ordre de - l/min sont obtenus. dès la mise en route du circuit, on observe une modeste amélioration de l'oxygénation, mais une normalisation rapide de la paco permettant de réduire les pressions et la fréquence du respirateur. dans une série de patients traités pour sdra ou pneumonie pour une durée moyenne de ± , jours, flörchinger et al. rapportent la néces sité de changer d'oxygénateur fois, suite à l'apparition de thrombus, la rétention de bulles d'air et de rares fuites plasmatiques. une thrombose complète du circuit est sur venue chez % des patients principalement du fait d'une anticoagulation insuffisante. une ischémie de membre est apparue dans % des cas nécessitant un changement de dimension de la canule ou de positionnement. un patient a dû subir une amputation de la jambe [ ] . dans une étude plus récente où le diamètre de la canule artérielle était choisi en fonction du diamètre échographique de l'artère et ne dépassait pas fr, l'incidence de complications ischémiques est tombée à % [ ] . la place exacte de cette approche reste cependant largement à préciser. une autre possibilité est d'utiliser un circuit veino veineux avec un cathéter unique à double lumière, une pompe créant des débits de , à l/min et un oxygénateur membranaire. cette technique a montré sa capacité à élimi ner une grande partie du co produit et à réduire la ventila tion mécanique, mais sa place dans le traitement du sdra reste à démontrer [ ] [ ] [ ] . conflit d'intérêt : le dr l. jacquet est consultant pour thoratec. extracorporeal life support organization registry report extracorporeal life support organization (elso) general guide lines for all ecls cases extreme nega tive pressure does not cause erythrocyte damage in flowing blood extracorporeal membrane oxyge nation for ards in adults wangzwische double lumen cannulatoward a percutaneous and ambulatory paracorporeal artificial lung insertion of bicaval dual lumen extracorporeal membrane oxygenation cathe ter with image guidance lowfrequency positive pressure ventilation with extracorporeal carbon dioxyde removal (lfppvecco r): an experimental study lower tidal volume strategy (~ ml/kg) combined with extracorporeal co removal versus "conventional" protective ventilation ( ml/kg) in severe ards. the prospective randomized xtraventstudy antithrombin deficiency in special clinical syndromes part i: extracorporeal membrane oxygenation atiii replacement during infant extracorporeal support comparison of a new heparincoated dense membrane lung with nonheparincoated dense membrane lung for prolonged extracorporeal lung assist in goats hemocompatibility of pmea coated oxygenators used for extracorporeal circulation procedures contemporary extra corporeal membrane oxygenation for adult respiratory failure: life support in the new era potential drug seques tration during extracorporeal membrane oxygenation: results from an exvivo experiment modified surface coa tings and their effect on drug adsorption within the extracorporeal life support circuit acquired von willebrand syndrome in patients with extracorporeal life support (ecls) current status of extracorporeal life support (ecmo) for cardiopulmonary failure referral to an extra corporeal membrane oxygenation center and mortality among patients with severe influenza a(h n ) the australia and new zealand extracorporeal membrane oxy genation (anz ecmo) influenza investigators ( ) extra corporeal membrane oxygenation for influenza a(h n ) acute respiratory distress syndrome argatroban usage for anticoagulation for ecmo on a postcardiac patient with hepa rininduced thrombocytopenia bioline hepa rincoated ecmo with bivalirudine anticoagulation in a patient with acute heparininduced thrombocytopenia: the immune reac tion appeared to continue impact of heparinin duced thrombocytopenia on outcome in patients with ventricular assist device support: a singleinstitution experience in conse cutive patients renal function and survival in patients undergoing ecmo therapy pumpless extracor poreal lung assist: a year institutional experience a novel extracorporeal co removal system. results of a pilot study of hypercapnic respira tory failure in patients with copd respiratory dialysis: reduction in dependence on mechanical ventilation by venovenous extracorporeal co removal single doublelumen venousvenous pumpdriven extracorporeal lung membrane support key: cord- -mgrxo j authors: lee, james c.; diamond, joshua m.; christie, jason d. title: critical care management of the lung transplant recipient date: - - journal: curr respir care rep doi: . /s - - - sha: doc_id: cord_uid: mgrxo j lung transplantation provides the prospect of improved survival and quality of life for patients with end stage lung and pulmonary vascular diseases. given the severity of illness of such patients at the time of surgery, lung transplant recipients require particular attention in the immediate post-operative period to ensure optimal short-term and long-term outcomes. the management of such patients involves active involvement of a multidisciplinary team versed in common post-operative complications. this review provides an overview of such complications as they pertain to the practitioners caring for post-operative lung transplant recipients. causes and treatment of conditions affecting early morbidity and mortality in lung transplant recipients will be detailed, including primary graft dysfunction, cardiovascular and surgical complications, and immunologic and infectious issues. additionally, lung donor management issues and bridging the critically ill potential lung transplant recipient to transplantation will be discussed. since the modern era of lung transplantation began in with the first series of successful human lung transplants [ ], there have been remarkable advances in this potentially lifesaving procedure for thousands of patients with end-stage lung and pulmonary-vascular diseases. however, the overall survival rates of lung transplant recipients in comparison to other solid organ transplant recipients is lagging, due in part to the unique technical, immunogenic, and infectious aspects of transplanting human lungs [ ] . in more recent eras, survival has improved, largely due to improvements affecting the early post-transplant period [ ] . despite these improvements, early morbidity and mortality remain important limiting factors for long term success; therefore, early recognition and management of problems that arise before and after lung transplantation in the intensive care unit setting are key to the long term success of the recipient. this review aims to summarize the most important aspects of the critical care management of the lung transplant recipient in the peri-operative time period [ ] [ ] [ ] [ ] . donor management in the icu the continued relative lack of supply of organs in contrast to the increasing demand for lung transplantation has spurred interest in expanding the traditionally accepted definition of the "ideal" lung donor, whose criteria of age < , pao > , minimal smoking history, and clear chest x-rays have contributed to lung acceptance rates of less than % [ ] . one avenue to expand the pool beyond this seemingly restrictive definition is the use of "extended donors" with liberalized selection criteria. some transplant centers have shown that the use of these donors have comparable shortterm outcomes to "ideal donors." other centers have described prolonged icu stays and increased early mortality with the use of donor lungs with infiltrates and/or purulent secretions [ ] [ ] [ ] [ ] [ ] . aggressive donor management by the team caring for a potential lung donor may result in the improvement of the function of "extended" donor lungs closer to the range of "ideal" organ and thus increasing lung donor conversion rates [ ] [ ] [ ] . a protocol-based approach for the management of potential organ donors, and particularly the ventilator management of potential lung donors, is an effective way to standardize variation in practice styles in the community as well as improve donor conversion rates. the university of texas at san antonio showed that with protocols designed to incorporate standardized lung recruitment maneuvers, aggressive donor fluid management, and aspiration-reduction precautions, rates of lung procurement can be significantly increased. of actual donors during a year protocol period, % were lungs from patients initially considered poor donors [ ] . a similar experience in quebec showed that simple lung recruitment protocols can be instituted safely and effectively to increase procurement rates and organ availability, of particular importance in large geographic areas with limited donors [ ] . education of intensivists on care of the brain dead patient is key, as proper management of such patients may affect both procurement rates as well as lead to improved immediate post-transplant outcomes. reviewed recently by naik and angel [ • ], brain death elicits hemodynamic instability, activation of inflammatory pathways, and endocrine dysfunction that can profoundly impacts the quality and function of the donated lungs. in conjunction with an active local donor procurement organization, active donor management is necessary to treat these homeostatic derangements. mascia et al. showed in a survey of icus in italy, that there is a clear tendency towards maintaining potentially injurious ventilatory management strategies and not performing recruitment maneuvers after the pronouncement of brain death [ ] . this same group also recently demonstrated beneficial effects of employing lung protective ventilatory strategies (tidal volume - mg/kg predicted body weight, peep - cm h o) on potential lung donors in a randomized controlled trial compared to conventional ventilatory parameters (tidal volume - mg/kg predicted body weight, peep - cm h o) [ ] . of patients enrolled into the study, % of donors from the lung protective ventilator strategy group went on to donate lungs vs. % of conventional ventilatory strategy group. six month outcomes of lung recipients from both groups did not differ [ ] . the management of the predisposing advanced lung diseases in lung transplant candidates who become acutely ill while awaiting lung transplantation can pose a challenge to the critical care practitioner. given the sometimes unpredictable nature of donor availability, the icu care of such patients has the potential to be prolonged, during which time-sensitive issues such as nutritional status, functional capacity, and infection avoidance in an effort to maintain listing eligibility become the focus of care. since the institution of the lung allocation score (las) in in the u.s. [ ] , the concept of net survival benefit as a balance of risk of death on the waitlist vs. chance of survival at year has driven organ allocation, often assigning the highest scores to patients who are acutely ill and mechanically ventilated. traditionally, requirement for mechanical ventilation had been viewed as a contraindication for active listing at most lung transplant centers due to the fear for poor outcomes. as described by mason et al., after querying the united network for organ sharing for lung transplantation from october through january , these fears are not unfounded [ ••] . the authors showed that of , transplants performed, patients were on mechanical ventilation and were on extracorporeal membrane oxygenation (ecmo) at the time of transplantation, both factors that contribute to the highest las scores. survival rates at , , , and months were significantly worse in both mechanical ventilation and ecmo supported; patients; for example, year survival was % for the ecmo bridged patients vs. % for the unsupported patients. those patients that received mechanical ventilation tended to be younger, have higher oxygen requirement, poorer renal function, and diagnoses other than emphysema such as cystic fibrosis. of note, the increase in mortality seen in patients with pre-operative mechanical ventilation or ecmo support seemed to be limited to the early time period after lung transplant; patients who required aggressive support pretransplant who survived the first months had comparable long-term survival to those not requiring pre-transplant support [ ••] . therefore, these historical administrative data suggest that improvements in the pre-operative morbidity of these procedures, such as reducing sedation, paralytics, or immobility in the pre-operative critical-ill patients, could lead to reasonable long-term outcomes. in recent years, pre-operative life support of the potential recipient has evolved. the concept of "bridging to transplantation" involves the use of mechanical support systems to sustain a patient in respiratory failure until the lung transplant can be performed, often with concurrent aggressive rehabilitation and physical therapy if at all possible [ ••, ] . similar to advances in mechanical circulatory support in heart transplantation, technical advances in the redesign of circulatory pumps, membrane oxygenators, and venous catheters has now made less invasive ecmo support feasible without immobilizing or paralyzing the patient in most cases. smaller, bilumen catheters, introduced into the jugular vein and the inferior and superior vena cava to drain venous blood and simultaneously provide oxygenated blood into the right atrium [ ] , may potentially allow patients to be awake, nonventilated, and ambulatory during ecmo support. as this field is rapidly evolving, further research will need to be done on selection of appropriate patients [ , •, - ] . the immediate post-operative period in the icu remains the most critical for the lung transplant recipient, requiring continuous hemodynamic monitoring, often maximal ventilatory support, and close observation of chest tube output for evidence of bleeding or other surgical complications. aggressive peri-operative antibiotic coverage is employed, often tailored to pre-transplant culture data, with consideration of induction immunosuppression. often, newly instituted transplant medications have the potential for unforeseen side effects on the kidneys, central nervous system, and other organs. the following sections highlight the most important critical care issues in the post-operative lung transplant recipient. a comprehensive list of peri-operative complications is listed in table . the various etiologies of respiratory failure following lung transplantation have been reviewed [ ••, , ] and will also be addressed in sections below. the most frequent and significant cause of early mortality after lung transplantation is primary graft dysfunction (pgd), a form of injury to the allograft resulting in large part from ischemia-reperfusion injury from the transplant process itself. pgd affects up to % of all lung transplants, and it leads to prolonged mechanical ventilation and icu length of stay, poor functional outcomes, and an increased risk of bronchiolitis obliterans syndrome (bos) [ , ] . in its most severe form, pgd presents as diffuse alveolar infiltrates in the allograft in the absence of cardiogenic pulmonary edema, infection, or cellular rejection that can lead to refractory hypoxia. several clinical risk factors for pgd have been described, to which malnutrition the icu physician should be attuned in order to assess the possibility of pgd in the critically ill lung transplant recipient. these include donor characteristics such as female gender, african-american race, extremes of donor age, elevated pulmonary arterial systolic pressure at the time of transplant, obesity and pre-existing diagnoses of pulmonary arterial hypertension and idiopathic pulmonary fibrosis [ ] [ ] [ ] [ ] . surgical and intra-operative risk factors for pgd include blood product administration, single transplant procedure and use of cardiopulmonary bypass [ ] [ ] [ ] [ ] [ ] . as most prior studies are hampered by small numbers, several of these risk factors have been inconsistently reported. ongoing multi-centered prospective studies are underway to better understand the clinical risk factors for severe pgd. treatment of pgd is supportive. other potentially reversible etiologies (table ) should be ruled-out utilizing the information available to the icu physician such as pulmonary arterial catheter measurements, cvp, radiographs, bronchoscopy, and echocardiography. mechanical ventilator support should be continued while simultaneously avoiding excessive colloid or crystalloid administration. diuresis should be initiated with blood pressure support if needed, as the lung parenchyma is damaged with evidence of capillary leak [ ] . theoretical benefits of lung protective ventilator strategies (low stretch, high peep) are extrapolated from the ards literature. as a rescue therapy, pressurecontrolled ventilation modes may be preferentially utilized to minimize barotrauma and airway/anastomosis complications. inhaled nitric oxide, while not proven to be effective in preventing pgd [ ] , may have benefit in improving oxygenation, reducing mean pulmonary arterial pressure, and increasing mean systemic arterial pressure in the first - h after transplant [ ] . ventilator management of pgd in single lung transplants with copd can be challenging. acute hyperinflation and significant v/q mismatch can occur, perhaps necessitating dual-lumen independent lung ventilation which can be logistically challenging for the icu staff. in severe and refractory cases, ecmo has been applied in those pgd cases not responsive to traditional mechanical ventilation. in the university of pittsburgh published their experience with ecmo in heart-lung and lung transplant recipients over a year period. of patients, . % required ecmo, instituted within the first days after transplant; of patients were successfully weaned off ecmo. thirty day-, year-, and year-survival in this group was %, %, and % respectively [ •] . in this severely ill population, it has been shown that late institution of ecmo, or inability to wean off ecmo, has led to near universal poor outcomes [ •, ] . most recently, hartwig et al. have investigated whether the use of venovenous ecmo and improvements in icu technology have affected outcomes. at a center where venovenous ecmo was the routine treatment for severe pgd, over a year period of time, of patients required ecmo. patients were able to be weaned from ecmo % of the time, and survival was better than in previous reports: %, %, and % at day, year and years, respectively. while encouraging, the authors did notice worse allograft function in ecmo survivors at years [ ••] . this study illustrates that with evolving technology and increased experience, venovenous ecmo may be successfully utilized in very select cases of profound respiratory failure following lung transplantation. the lung transplant recipient with elevated pulmonary arterial pressures at the time of transplant or an underlying diagnosis of pulmonary arterial hypertension requires particularly close attention immediately after lung transplantation. the proper care of such patients begins prior to surgery, as the anesthesiologist should be vigilant to avoid sudden rises in pulmonary vascular resistance and subsequent right heart failure [ •]. intra-operative transesophageal echocardiography can be a useful tool to evaluate right ventricular function. pulmonary vasodilators such as inhaled nitric oxide, milrinone, and inhaled prostacyclin can reduce right ventricular afterload and expedite recovery of the rv in the post-operative state [ • ]. most transplant recipients will require vasopressors during the surgical procedure, and it is not uncommon to return to the icu with vasopressors being administered with the expectation of quick weaning of such agents. fluid management should be aimed at maintaining cardiac output but also minimizing pulmonary edema with active use of pulmonary arterial catheter measurements or echocardiography if available. arrhythmias after lung transplant are typically supraventricular in origin and are common, ranging between % and %. older patients seem particularly at risk for this complication [ ] . in a recent review of lung transplant recipients, atrial fibrillation occurred in % of patients within days after surgery, with a mean onset at . +/- days. mean icu stay and hospital stays are lengthened when atrial arrhythmias are experienced [ ] . in the icu, hemodynamically significant arrhythmias should be treated aggressively with cardioversion when indicated; otherwise, medical management will usually suffice. if these issues persist, consideration should be given to antiarrhythmic administration such as amiodarone, as well as initiation of anticoagulation. when bleeding complications are concurrent, this can be problematic. the propensity for intra-operative bleeding in lung transplant recipients can often be anticipated prior to the surgical procedure, with proper precautions taken. recipients with an underlying history of heart disease with coronary stents in place may chronically be on antiplatelet agents such as clopidogrel, which will increase the risk of bleeding substantially. additionally, patients with severe pulmonary hypertension may be on warfarin therapy that requires reversal. the explantation of native lungs can also lead to substantial bleeding; scarred lung parenchyma may be fibrotic and adherent to pleural surfaces, or inflamed and associated with chronic foci of infection such as in sarcoidosis or cystic fibrosis patients. other infections such as aspergillomas with reactive pleural involvement sometimes pose a prohibitive risk for bleeding during the explantation of native lungs and can lead to operative demise if significant. in the post-operative setting, bleeding risk must be monitored through serial laboratory studies, chest tube drainage measurements, and radiographs. rapidly enlarging effusions or "white out" of a lung field may indicate a significant pleural bleed, which may not be appreciated based on recorded output alone should the chest tube malfunction or be improperly positioned. differences in size matching present special challenges for management of the lung transplant recipient. lung transplant recipients with fibrotic lung diseases will tend to have smaller thoracic cavities for their height, and because of this, there may be difficulties finding properly size-matched donors. donor lungs may be volume reduced intraoperatively using linear stapling, though potential complications from this type of procedure include air leaks and bronchopleural fistula formation [ ] . if lungs are too big for the chest cavity in the immediate postoperative period, the team may choose to delay chest closure if the median sternotomy approach is used, for instance. in the post-operative state, patients with open chests require specialized nursing attention and broadened antibiotic and antifungal coverage. size mismatches of donor lungs that are too small for a thoracic cavity may lead to persistent pleural effusions and high chest tube output. in these situations, chest wall remodeling may occur over time or the recipient may be left with chronic post-operative effusions. vascular anastomotic complications can lead to severe and sudden compromise in the lung transplant recipient. fortunately, these are rare, but may carry high mortality. pulmonary arterial stenosis or thrombus formation typically presents with hypotension and evidence of right heart failure. pulmonary venous thrombosis, usually in proximity to the pulmonary vein-left atrial anastomosis typically presents with hypotension and either lobar or diffuse pulmonary edema with refractory hypoxemia (fig. ) [ ] . because of the rarity of these conditions, diagnosis can be difficult and requires a high index of suspicion. urgent transesophageal echocardiography should be performed at the bedside for patients with a rapid change of course for diagnosis before potential surgical intervention. thrombolysis is a high-risk intervention that can be considered for pulmonary vein thrombosis [ ] ; however, management usually involves surgical re-exploration. in the immediate post-operative state, the bronchial anastomoses are prone to complications due to the bronchial circulation being sacrificed during the transplant procedure. this relative ischemia may then be exacerbated by intra-or post-operative hypotension or other hemodynamic fluctuations, making the anastomosis susceptible to necrosis, dehiscence, and infection. frank bronchial dehiscence is rare, on the order of %; partial dehiscence can be addressed with the temporary placement of self-expanding wire stents to encourage granulation tissue growth and healing [ ••, , ] . in most lung transplant programs, it is the general practice to sacrifice the bronchial arterial supply when implanting the newly transplanted lung. in spite of concerns that bronchial artery revascularization (bar) prolongs ischemic time and increases operative risk of bleeding, centers who routinely employ bar argue for potential benefits of fewer airway complications and reduced bos risk [ ] [ ] [ ] [ ] . before bar can be advocated for widespread use, extension of these techniques to a broader range of centers with consistent surgical competency needs to be addressed. hyperacute and acute rejection hyperacute rejection is a distinct and rare form of lung rejection and is described mostly in case reports [ ] [ ] [ ] [ ] [ ] [ ] . it is characterized by an early and rapid onset, minutes to hours after reperfusion, and is the result of preformed recipient antibodies causing profound allograft dysfunction via mechanisms such as complement activation from abo incompatibility or unrecognized significant anti-hla antibodies to the donor. clinically, one sees pink frothy sputum, profound hypoxemia, and pathologically a coagulopathy with fibrin and platelet thrombi formation within minutes to hours of reimplantation. the first case report appeared in as described by frost et al. and illustrates the typical presentation: the patient described was a single lung recipient who tolerated a few hours of hyperacute rejection [ ] . the patient had a history of two pregnancies, no blood transfusions, and a calculated pra was approximately %. three hours after implantation a donor specific class i antibody to b was identified. the patient underwent treatment with plasmapheresis, cytoxan, and ultimately the allograft was removed and the patient relisted for re-transplant. the recipient died days later before another donor could be identified [ ] . other case reports detail patient survival after suspected hyperacute rejection with similarly aggressive immunosuppression regimens [ ] . although traditionally thought not to occur in the days following transplantation, acute cellular rejection can be seen as early as a week after transplant, and it can make treatment of other icu complications difficult. for instance, during treatment of profound infections in critically ill lung transplant recipients, targeted immunosuppression levels may be lowered or agents stopped altogether in efforts to allow the patient to fend off the current infection. beyond the initial hospitalization, acute cellular rejection is a common occurrence especially in the first year post-transplant, monitored with surveillance bronchoscopy with transbronchial biopsies. the initiation of several immunosuppressive agents in the early post-operative period not only predisposes the transplant recipient to infectious complications, but can cause transient renal dysfunction that may be exacerbated by other concurrent medical complications. the calcineurin inhibitors tacrolimus and cyclosporine are the main culprits for acute renal dysfunction. these agents induce vasoconstriction of the afferent renal arteriole leading to reduction of renal blood flow and glomerular filtration rate. if the critically ill lung transplant recipient experiences peri-operative hypotension, aggressive diuresis for pgd, and is on numerous potentially other nephrotoxic medications, renal dysfunction may be prolonged and severe, leading to serious long-term complications. in a series of lung and heartlung transplant recipients surviving at least months, . % had a decrease in kidney function, and end stage renal disease occurred in . % at a median duration of months [ ] . infectious complications are a frequent and important cause of morbidity and mortality in the post-operative lung transplant recipient. in addition to the relatively high levels of immunosuppression required by lung transplant recipients, the lungs are unique when compared to other solid organ transplants in that they are continually exposed to the external environment, thereby putting the allografts at risk for many more potential infectious insults. this section will focus on the infectious issues surrounding the care of the lung transplant recipient in the immediate post-operative time period. pre-transplant culture data are vitally important when caring for lung transplant recipients in the icu. ideally patients with underlying suppurative lung diseases such as bronchiectasis or cystic fibrosis will have recent culture data with which to guide immediate antibiotic therapy choices in the post-operative period. organisms such as multi-drug resistant pseudomonas species, methicillin resistant staph aureus, rapidly-growing nontuberculous mycobacteria (ntmb), and fungal organisms will directly impact peri-operative antibacterial and antifungal choices and will likely affect treatment duration as well. in patients with cystic fibrosis, the sinuses and upper respiratory tract may be a reservoir for ongoing infections and therefore aggressive antibiosis and prolonged therapy is often necessary. cultures taken intra-operatively, from bronchoscopy performed after bronchial anastomoses are completed, as well as pleural and chest wall cultures can be very useful as well. the former provide up-to-date sampling of the potential donor flora, which can be used in conjunction with cultures obtained from the donor site to help guide antibiotic therapy. chest cavity cultures can be helpful in recipients with structurally abnormal lungs (e.g. cavitary lesions) or parenchymal pulmonary nodules that may be suspicious for chronic infections such as aspergillus species or ntmb. culture data from the organ donor may potentially affect post-transplant care in the icu. as lung donors are ventilator-dependent, tracheal aspirate cultures are routinely performed, as well as blood and urine cultures. however, such information may not be readily available at the time of transplant, so any significant change in postoperative course or concern for progressing infection in the recipient should prompt an investigation into the results of donor cultures. empiric broad spectrum perioperative antibiotic prophylaxis is often employed, but the decision to continue such treatment is on a case-bycase basis, often impacted by information derived from donor culture results. viral infections in the post-operative state are rare, but conceivably can either be transmitted via the donor or result from an early or subclinical respiratory virus in the recipient at the time of surgery and induction immunosuppression. recipients may have been exposed to community acquired viruses such as respiratory syncytial virus, adenovirus, parainfluenza, and influenza, which may become clinically apparent in the peri-operative period as fulminant respiratory or systemic infections. in contrast, although cmv is a commonly seen viral pathogen in post-transplant patients, overwhelming cmv infection is rare in the immediate post-operative state in the modern era. most centers will institute cmv prophylaxis of varying duration depending on the cmv status of the donor and recipient. due to the wide variety of common and opportunistic infections to which the lung transplant population is susceptible, it is often prudent for the icu practitioner to employ the expertise of transplant infectious disease specialists to help manage such cases. in addition, the presence of a dedicated transplant pharmacist as part of the multidisciplinary team is helpful in monitoring for significant medication interactions that affect serum drug levels and for side effects such as nephrotoxicity. the care of the lung transplant recipient in the immediate post-operative period is a complex undertaking that requires a multidisciplinary team led by the icu practitioner working in conjunction with the transplant medical and surgical teams. the lung transplant recipient is at risk for several categories of complications. with donor supply shortages and increasing numbers of patients awaiting transplant, the scenario of employing more extended criteria lungs in increasingly critically ill recipients at the time of transplant is becoming more likely. great care must be taken to reduce the impact of immediate post-operative morbidity on long term outcomes in this population. disclosure no potential conflicts of interest relevant to this article were reported. lung transplantation for pulmonary fibrosis. toronto lung transplant group the registry of the international society for heart and lung transplantation: twentyeighth adult lung and heart-lung transplant report management of the patient undergoing lung transplantation: an intensive care perspective critical care aspects of lung transplantation lung transplantation: donor and recipient critical care aspects perioperative management 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blood transfusion, and risk of primary graft dysfunction cardiopulmonary bypass is associated with early allograft dysfunction but not death after double-lung transplantation early lung allograft function in twin recipients from the same donor: risk factor analysis lung transplant for interstitial lung disease: outcomes for single versus bilateral lung transplantation report of the ishlt working group on primary lung graft dysfunction part vi: treatment a randomized trial of inhaled nitric oxide to prevent ischemia-reperfusion injury after lung transplantation effects of inhaled nitric oxide following lung transplantation extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival institution of extracorporeal membrane oxygenation late after lung transplantation -a futile exercise? improved survival but marginal allograft function in patients treated with extracorporeal membrane oxygenation after lung transplantation anesthetic management for lung transplantation atrial fibrillation, atrial flutter, or both after pulmonary transplantation systemic recombinant tissue plasminogen activator lysis for left atrial thrombus formation after single-lung retransplantation endobronchial stent placement for the management of airway complications after lung transplantation short-term deployment of self-expanding metallic stents facilitates healing of bronchial dehiscence lung transplant airway hypoxia: a diathesis to fibrosis? airway complications after lung transplantation can be avoided without bronchial artery revascularization bronchial blood supply after lung transplantation without bronchial artery revascularization bronchial artery revascularization in lung transplantation: techniques, experience, and outcomes hyperacute rejection in single lung transplantation-case report of successful management by means of plasmapheresis and antithymocyte globulin treatment fulminant hyperacute rejection after unilateral lung transplantation hyperacute rejection of a pulmonary allograft. immediate clinical and pathologic findings hyperacute rejection after single lung transplantation: a case report hyperacute rejection following lung transplantation hyperacute rejection after lung transplantation caused by undetected low-titer anti-hla antibodies predictors of renal function following lung or heart-lung transplantation key: cord- - q cno authors: pham, t.; richard, j. -c.; brochard, l. title: assistance par circulation extracorporelle veinoveineuse dans le traitement du syndrome de détresse respiratoire aiguë : rationnel et objectifs cliniques date: - - journal: reanimation doi: . /s - - - sha: doc_id: cord_uid: q cno extracorporeal circulation techniques can be used for the management of severe respiratory failure complicating the acute respiratory distress syndrome with three objectives: ) to ensure satisfying oxygenation by bypassing the sick lung using a veno-venous circulation with high blood flows; this technique easily extracorporeal permit co( ) elimination; ) to ensure partial elimination of co( ) with the aim to protect the lungs from risky mechanical ventilation. four to five times lower blood flows are sufficient with a veno-venous circulation or pumpless arterio-venous techniques; ) associated cardiac failure may exceptionally require veno-arterial extracorporeal circulation. physiological studies and clinical trials are absolutely needed to better delineate the indications of these techniques. l'assistance respiratoire par circulation extracorporelle (cec) veinoveineuse dans le traitement du syndrome de détresse respiratoire aiguë (sdra) répond à un certain nombre d'objectifs qui ont évolué au cours du temps et en fonction des techniques. dans cette optique, il est important de distinguer brièvement les trois types de techniques qui ont été parfois mélangées sous le terme d'assistance et d'oxygénation extracorporelle ou extracorporeal membrane oxygenation (ecmo). l'acronyme arec pour « assistance respiratoire extracorporelle » regroupe aussi ces différentes méthodes. ces techniques sont des versions simplifiées et améliorées des systèmes de cec développés pour la chirurgie cardiaque depuis les années et utilisant le plus souvent une canulation dans l'aorte et les veines caves : • l'assistance par cec veinoartérielle a pour objectif de soutenir et/ou remplacer une circulation défaillante tout en apportant du sang oxygéné [ ] . elle est posée le plus souvent en percutané, par opposition à la pose centrale telle qu'elle est effectuée en chirurgie cardiaque lors d'une cec. elle nécessite des débits relativement élevés ( - l/min), une anticoagulation, et court-circuite à la fois les poumons et le coeur en renvoyant le sang oxygéné directement dans la circulation artérielle à contre-courant. en position fémorofémorale et malgré une reperfusion systématique de l'artère fémorale, la canule artérielle a un diamètre limité afin d'éviter l'une des complications principales, l'ischémie fémorale ; c'est le principal paramètre limitant le débit ; • l'assistance par cec veinoveineuse a pour objectif de soutenir et/ou remplacer une oxygénation pulmonaire défaillante [ ] . afin d'éviter que le débit de sang natif passant par les poumons malades ne reste élevé et rentre en compétition avec l'oxygénation extracorporelle, des canules de gros calibre permettant un débit d'extraction de sang veineux élevé ( - l/min) sont nécessaires. les deux principales limitations à l'obtention des objectifs d'oxygénation sont un débit sanguin insuffisant par rapport à la circulation propre du patient et le phénomène de recirculation : lorsque les extrémités des deux canules insérées dans le système cave sont trop proches, le sang oxygéné réinjecté peut être réaspiré plutôt que de retourner dans la circulation du patient via l'oreillette droite. ce phénomène est majoré en cas d'hypovolémie et de faible débit cardiaque. une surveillance échographique est nécessaire afin de régulièrement vérifier la position des canules. l'assistance par cec veinoveineuse avec une pompe ou artérioveineuse sans pompe (la pression artérielle du patient assurant la circulation) peut avoir pour objectif principal de soutenir et/ou remplacer une élimination de co pulmonaire insuffisante [ ] [ ] [ ] [ ] . cet objectif peut être en général assez facilement atteint avec des débits sanguins proches de ceux d'une hémofiltration, beaucoup moins importants que l'indication précédente si l'indication principale de la technique semble être d'assurer l'oxygénation, c'est en fait le plus souvent d'assurer cette oxygénation à moindre risque que par une prise en charge traditionnelle. les possibles indications de la technique dans le sdra sont résumées dans le tableau . cette indication apparemment simple pose en fait deux questions essentielles : quelles sont les limites tolérables de l'hypoxémie artérielle et quels sont les risques respectifs des deux types de prise en charge (traditionnelle versus ecmo). on n'a guère avancé sur la première question en termes d'évidence scientifique. À l'inverse, d'une part l'état des connaissances a considérablement évolué sur les risques de la prise en charge traditionnelle par ventilation mécanique, et d'autre part les améliorations technologiques ont permis une réduction des complications. ainsi, de façon générale, bien que le pronostic des patients les plus graves pris en charge avec une ventilation conventionnelle se soit significativement amélioré, le rapport risque/bénéfice, central dans cette indication, semble avoir un peu évolué en faveur de l'ecmo [ ] [ ] [ ] . de plus, beaucoup de données suggèrent que le pronostic des patients mis en ecmo après une durée prolongée de ventilation est nettement moins bon que celui de ceux chez qui la technique est débutée précocement [ ] . ces données sont difficiles à interpréter, car il existe un biais de sélection évident, mais elles incitent à prendre des décisions rapidement avant que des seuils de sévérité évidents ne soient atteints. enfin, si les données sur la survie ne sont pas tranchées, l'ecmo ne semble pas avoir d'effets à long terme plus négatifs que la ventilation mécanique traditionnelle [ , ] . ce sont donc les complications à court terme qui vont avant tout peser dans la balance. la première indication est d'assurer une oxygénation défaillante. cet objectif apparemment intuitif se heurte à plusieurs éléments objectifs qui nous manquent. la limite de l'hypoxémie artérielle tolérable est difficile à déterminer de même que les risques de fraction inspirée d'oxygène (fio ) élevée. la pente de la courbe de dissociation de l'hémoglobine suggère qu'en dessous de % de saturation artérielle, le contenu en oxygène chute de manière directement et quasi linéairement proportionnelle à la pao . mais la survie à des niveaux d'hypoxémie artérielle apparemment très bas est possible. les limites semblent même repoussées lorsqu'on constate que les pao artérielles au sommet de l'everest (en hypoxie hypobare, avec une pression atmosphérique de mmhg) sont inférieures à mmhg et une saturation artérielle proche de % [ ] . il est vrai qu'il s'agit alors de sujets en bonne santé, entraînés et s'étant accoutumés à l'altitude avec des taux d'hémoglobine proches de g/dl, amenant le contenu artériel à un peu moins de ml d'o /l, soit l'équivalent du contenu du sang veineux chez l'adulte. pour mémoire, un patient de soins intensifs avec un taux d'hémoglobine de g/dl, une pao de mmhg et une sao de % a un contenu artériel de ml d'o /l. comme on le voit, le contenu est souvent ignoré et encore plus le transport en oxygène sous la dépendance du débit cardiaque. indiscutablement, l'hypoxémie sévère associée à des difficultés ventilatoires majeures a été à l'origine de la « redécouverte » de cette technique à l'occasion des épidémies de sdra liées au virus h n [ , , ] . si l'hypoxémie permissive est donc un concept régulièrement discuté, il n'est pas accepté en pratique clinique, et l'indication d'hypoxémie concernant des pao inférieures à mmhg et/ou des sao inférieures à - % pour des fio quasi maximales (≥ %) reste très largement admise comme une possible indication d'ecmo. celle-ci devrait être idéalement adaptée au transport en oxygène (hémoglobine, débit cardiaque) et aux conséquences tissulaires (lactates élevés, ischémie coronaire, insuffisance rénale [ ] ). enfin, il semble que la sévérité de l'hypoxémie dans l'insuffisance respiratoire aiguë soit corrélée à la survenue de dysfonction cérébrale à distance [ ] , ce qui tendrait à être prudent sur le degré d'hypoxémie tolérable. les recommandations faites par le réseau de recherche reva au moment de l'épidémie de grippe h n et des [ ] . parallèlement, d'autres données observationnelles suggéraient qu'une stratégie de ventilation conventionnelle limitant le recours à l'ecmo dans cette indication permettait d'obtenir une survie très acceptable chez des malades au sdra apparemment très sévère [ , ] . les résultats cliniques en france ont montré que les cliniciens ont plutôt suivi ces indications avec cependant une probable sous-utilisation du décubitus ventral et un recours plus rapide chez les patients jeunes et les femmes enceintes [ , [ ] [ ] [ ] . les résultats n'ont pas été aussi favorables que dans les séries d'océanie. cela pourrait s'expliquer par une utilisation trop large avec moins de sélection sur l'âge et les comorbidités, voire un manque d'expérience reflété par exemple par le recours dans % des cas aux ecmo veinoartérielles qui ont de nettement moins bons résultats dans cette indication en dehors d'une dysfonction cardiaque sévère associée. le projet multicentrique eolia (http://clinicaltrials. gov/show/nct ) cherche à tester si l'utilisation de l'ecmo en technique de sauvetage diminue la mortalité. les indications de la technique dans le bras ecmo sont données dans le tableau . cette étude, dirigée par le pr a. combes, est en cours et devrait apporter des réponses importantes dans les deux prochaines années. la vision traditionnelle est de considérer qu'une pression de plateau supérieure à - cmh o est très fortement liée à la survenue de lésions liées à la ventilation et peut donc faire discuter le passage à l'ecmo si la paco n'est plus maîtrisée. sur ce dernier point, les limites de la paco tolérables ne sont pas connues et dépendent certainement de la vitesse d'installation d'une hypercapnie. en effet, à la vasodilatation systémique s'oppose une vasoconstriction pulmonaire particulièrement risquée dans les situations de coeur pulmonaire aigu ou même simplement d'hypertension artérielle pulmonaire [ ] . enfin, on a connu un enthousiasme initial sur l'acceptabilité de l'hypercapnie permissive [ , ] , puis la notion d'une possible hypercapnie thérapeutique [ ] [ ] [ ] [ ] . on est aujourd'hui redevenu beaucoup plus prudent, en particulier à cause des effets de l'hypercapnie altérant les fonctions des polynucléaires neutrophiles et favorisant l'infection [ ] [ ] [ ] . À l'inverse, on est aujourd'hui de plus en plus tenté d'imaginer qu'une technique d'épuration de co (il existe des systèmes artérioveineux sans pompe ou des systèmes veinoveineux avec pompes) puisse être utilisée pour réduire la demande faite au système respiratoire et les risques de la ventilation mécanique. la limite de pression tolérable est peut-être souvent en dessous des - cmh o classiques comme suggéré par certaines études [ , ] [ ] . les résultats n'ont pas montré de différence de survie (environ , % de mortalité) ou de durée de séjour, mais ont montré la faisabilité de la technique. ces résultats très préliminaires sont encourageants pour lancer des projets prospectifs multicentriques dans cette indication. aujourd'hui, l'impossibilité de maintenir des pressions raisonnables (≤ , ou cmh o ?) avec une paco déjà élevée (≥ mmhg) est acceptée comme un critère de mise possible sous ecmo. dans l'avenir, la possibilité de délivrer des ventilations ultraprotectrices (peep élevée pour maintenir le poumon relativement ouvert et réduire les risques de lésions d'ouverture-fermeture) et un vt suffisamment petit (≤ ml/kg de poids prédit) pour maintenir des pressions de plateau inférieures à cmh o est une stratégie intéressante, mais dont le bénéfice n'a pas été formellement démontré. cela doit être modulé par l'état des connaissances qui nous apportent deux éléments importants. le premier est l'intérêt majeur de la mesure de la pression transpulmonaire afin d'évaluer la réelle pression de distension du poumon sans s'arrêter à la pression de plateau mesurée dans les voies aériennes. comme l'a suggéré le travail de grasso et al. [ ] , cette mesure doit pouvoir éviter des mises sous ecmo inappropriées. en effet, les patients chez qui la paroi thoracoabdominale influence fortement les pressions statiques des voies aériennes peuvent bénéficier de pressions supplémentaires en restant dans une zone peu à risque de distension. cette mesure peut également permettre un meilleur réglage de la peep, et donc une meilleure oxygénation [ ] . sur malades avec un sdra répondant aux critères de recours à l'ecmo, ces auteurs montraient que l'augmentation de la peep guidée par la mesure de la pression transpulmonaire permettait d'éviter l'ecmo dans % des cas, car une proportion importante des pressions étaient expliquées par la paroi et non par la distension pulmonaire ( ) . la seconde réserve dans l'indication de l'ecmo est le bénéfice apporté par le décubitus ventral aux patients atteints d'un sdra sévère [ ] , qui peut faire fréquemment repousser l'indication de cette technique. tableau indications de l'ecmo testées dans l'étude eolia (clinicaltrials.gov identifier : nct . promoteur : assistance publique-hôpitaux de paris) un des trois critères de gravité suivants : . pao /fio < mmhg en fio > % pendant plus de trois heures malgré optimisation de la ventilation mécanique protectrice (peep ≥ cmh o, vt < ml/kg de poids prédit, pplat < cmh o) et recours aux thérapeutiques adjonctives habituelles (no inhalé, décubitus ventral, perfusion d'almitrine) ou . pao /fio < mmhg en fio > % pendant plus de six heures malgré optimisation de la ventilation mécanique protectrice (peep ≥ cmh o, vt < ml/kg de poids prédit, pplat < cmh o) et recours aux thérapeutiques adjonctives habituelles (no inhalé, décubitus ventral, perfusion d'almitrine) ou . ph < , pendant plus de six heures (malgré augmentation de la fr jusqu'à /minute) avec paramètres de ventilation mécanique ajustés pour maintenir une pplat ≤ cmh o (réduction du vt à ml/kg par paliers de ml/kg ≤ ml/kg puis de la peep à un minimum si l'indication d'une ecmo a été posée dans le cadre d'un sdra, le ventilateur doit être réglé de façon à minimiser le traumatisme induit par la ventilation mécanique. comme on l'a vu, le contrôle de la paco est obtenu très facilement avec l'ecmo et permet de réduire le vt, élément clé de la stratégie. les paramètres suivants sont alors proposés pendant la période initiale d'assistance par ecmo : mode assisté-contrôlé en pression ou en volume, fio entre et %, peep maintenue pour éviter trop de dérecrutement du poumon, vt réduit afin d'obtenir une pression de plateau inférieure à cmh o et une fréquence respiratoire basse. À ce titre, les données obtenues à partir de la cohorte française d'ecmo lors de l'épidémie de grippe h n sont importantes [ ] . elles suggèrent en effet que le maintien d'une pression de plateau inférieure ou égale à cmh o est un facteur indépendamment associé à un meilleur pronostic. cela indique d'une part que la protection pulmonaire est un élément majeur de la prise en charge sous ecmo, et d'autre part que cette protection pulmonaire ne peut être réalisée que si l'ecmo est efficace, et vraisemblablement avec des débits sanguins suffisants. le maintien d'une ventilation spontanée dans cette période n'est pas impossible, mais n'est pas la règle. ces patients ont en effet une stimulation des centres respiratoires très importante qui peut rester élevée malgré la baisse de la paco sous ecmo et sont d'autre part extrêmement restrictifs et difficiles à ventiler dans ces conditions [ ] . on pourra essayer des modes proportionnels ou des modes non synchronisés en se méfiant des volumes courants possiblement élevés qui peuvent être générés. possiblement, on tentera des modes en pressions non synchronisées en se méfiant des volumes courants qui peuvent être générés, ou des modes proportionnels. la membrane d'oxygénation et le circuit d'ecmo ne doivent être remplacés que si l'on soupçonne son dysfonctionnement (dépôts de fibrine ou de caillots sur la membrane, caillotage, augmentation du gradient de pression transfiltre, défaut d'oxygénation ou d'épuration du co par la membrane, hémolyse intravasculaire) ou systématiquement après une à trois semaines de fonctionnement. des gaz du sang peuvent être prélevés à la sortie de l'oxygénateur en cas de doute sur son fonctionnement. en cas d'hypoxémie (pao < mmhg) mesurée à la sortie de l'oxygénateur malgré une fio à %, il est recommandé de changer le circuit [ ] . le sevrage d'une ecmo veinoveineuse implantée dans le cadre d'une défaillance respiratoire peut être envisagé lorsqu'une amélioration clinique, gazométrique, radiologique et de la compliance pulmonaire est constatée. ce test de sevrage de l'ecmo doit être envisagé très précocement et quotidiennement, car une prolongation inutile de l'ecmo peut être délétère. une épreuve de sevrage de l'ecmo peut être réalisée en arrêtant la ventilation de la membrane et en ajustant la fio de l'ecmo à % et le débit d'assistance à - , l/min. parallèlement, les réglages du ventilateur doivent être réadaptés selon un mode conventionnel. en cas d'épreuve de sevrage prolongée, l'oxygénateur à membrane sera balayé par l'admission de mélange gazeux à fort débit toutes les heures pendant secondes. le retrait de l'ecmo peut être envisagé en fonction de la pao avec une fio sur le respirateur inférieure à %, de la pression plateau, de la paco , du ph artériel et s'il n'apparaît pas de signes de coeur pulmonaire aigu à l'échographie cardiaque (tableau ). les techniques d'oxygénation par cec ou ecmo se sont améliorées et miniaturisées, et nécessitent aujourd'hui moins d'anticoagulation exposant les patients à un risque de complication hémorragique moindre. elles permettent de réoxygéner le sang en cas de défaillance respiratoire sévère, à condition de fonctionner avec un débit sanguin élevé nécessitant des canules de fort calibre. leur autre intérêt majeur est de permettre une ventilation résiduelle beaucoup moins agressive et protégeant le poumon. dans cette optique, une canulation adéquate et un circuit veinoveineux sont recommandés. si la technique semble intéressante à titre de sauvetage, l'amélioration de la prise en charge par ventilation mécanique et techniques adjuvantes a permis d'améliorer la mortalité, remettant perpétuellement en balance les bénéfices/risques des deux techniques. la facilité avec laquelle cette technique peut participer à l'élimination de co en fait également un outil très attractif en vue de réduire les risques de la ventilation. les indications pourraient être potentiellement nettement plus larges que l'hypoxémie réfractaire, en particulier parce que les débits sanguins nécessaires nettement plus faibles rendent la technique potentiellement plus simple à utiliser. là non plus, cependant, nous ne disposons pas de preuves d'un bénéfice/ risque clairement en faveur des techniques. dans tous les cas, des études physiologiques et des essais contrôlés paraissent indispensables pour avancer dans les indications. extracorporeal membrane oxygenation for ards in adults extracorporeal carbon dioxide removal for refractory status asthmaticus: experience in distinct exacerbation phenotypes treatment of acute respiratory failure with low-frequency positive-pressure ventilation and extracorporeal removal of co tidal volume lower than ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial 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outcomes study: long-term neuropsychological function in survivors of acute lung injury should we "rescue" patients with influenza a(h n ) and lung injury from conventional mechanical ventilation? clinical findings and demographic factors associated with icu admission in utah due to novel influenza a(h n ) infection french experience of a/h n v influenza in pregnant women adult intensive-care patients with pandemic influenza a(h n ) infection interest of a simple on-line screening registry for measuring icu burden related to an influenza pandemic impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome low mortality rate in adult respiratory distress syndrome using lowvolume, pressure-limited ventilation with permissive hypercapnia: a prospective study bench-to-bedside review: carbon dioxide therapeutic hypercapnia: careful science, better trials permissive hypercapnia: role in protective lung ventilatory strategies hypercapnia in acute illness: sometimes good, sometimes not hypercapnia impairs lung neutrophil function and increases mortality in murine pseudomonas pneumonia elevated co suppresses specific drosophila innate immune responses and resistance to bacterial infection tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome tidal recruitment and overinflation in acute respiratory distress syndrome: yin and yang lower tidal volume strategy ( approximately ml/kg) combined with extracorporeal co removal versus "conventional" protective ventilation ( ml/kg) in severe ards: the prospective randomized xtravent-study ecmo criteria for influenza a(h n )-associated ards: role of transpulmonary pressure mechanical ventilation guided by esophageal pressure in acute lung injury prone positioning in severe acute respiratory distress syndrome patient-ventilator interaction in ards patients with extremely low compliance undergoing ecmo: a novel approach based on diaphragm electrical activity assistance cardiorespiratoire par extracorporeal membrane oxygenation (ecmo) key: cord- -a bspoii authors: roch, antoine; hraiech, sami; masson, elodie; grisoli, dominique; forel, jean-marie; boucekine, mohamed; morera, pierre; guervilly, christophe; adda, mélanie; dizier, stéphanie; toesca, richard; collart, fréderic; papazian, laurent title: outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center date: - - journal: intensive care med doi: . /s - - - sha: doc_id: cord_uid: a bspoii purpose: patients with severe acute respiratory distress syndrome (ards) are candidates for extracorporeal membrane oxygenation (ecmo) therapy. the evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. this study was designed to identify early factors associated with hospital mortality in ards patients treated with ecmo and retrieved from referring hospitals. methods: data from consecutive ards patients equipped with ecmo by our mobile team and consequently admitted to our icu were prospectively collected and analyzed. results: the main ards etiologies were community-acquired bacterial pneumonia ( %), influenza pneumonia ( %) (with patients having been treated during the first half of the study period), and nosocomial pneumonia ( %). the median (interquartile range) time between contact from the referring hospital and patient cannulation was ( – ) h. ecmo was venovenous in ( %) patients. no complications occurred during transport by our mobile unit. forty-eight patients died at the hospital ( %). based on a multivariate logistic regression, a score including age, sofa score, and a diagnosis of influenza pneumonia was constructed. the probability of hospital mortality following ecmo initiation was % in the – score class (n = ) and % in the – score class (n = ). patients with an influenza pneumonia diagnosis and a sofa score before ecmo of less than had a mortality rate of %. conclusions: age, sofa score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ards patients considered for retrieval under ecmo from distant hospitals. abstract purpose: patients with severe acute respiratory distress syndrome (ards) are candidates for extracorporeal membrane oxygenation (ecmo) therapy. the evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. this study was designed to identify early factors associated with hospital mortality in ards patients treated with ecmo and retrieved from referring hospitals. methods: data from consecutive ards patients equipped with ecmo by our mobile team and consequently admitted to our icu were prospectively collected and analyzed. results: the main ards etiologies were community-acquired bacterial pneumonia ( %) , influenza pneumonia ( %) (with patients having been treated during the first half of the study period), and nosocomial pneumonia ( %) . the median (interquartile range) time between contact from the referring hospital and patient cannulation was ( ) ( ) ( ) ( ) h. ecmo was venovenous in ( %) patients. no complications occurred during transport by our mobile unit. forty-eight patients died at the hospital ( %). based on a multivariate logistic regression, a score including age, sofa score, and a diagnosis of influenza pneumonia was constructed. the probability of hospital mortality following ecmo initiation was % in the - score class (n = ) and % in the - score class (n = ). patients with an influenza pneumonia diagnosis and a sofa score before ecmo of less than had a mortality rate of %. conclusions: age, sofa score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ards patients considered for retrieval under ecmo from distant hospitals. the technique of extracorporeal membrane oxygenation (ecmo) for patients with severe acute respiratory distress syndrome (ards) involves placing them on a venovenous or venoarterial life-support circuit with a membrane oxygenator to temporarily take over the gas exchange and, sometimes, cardiac function [ ] . over the last two decades, the technique has progressed significantly, and several studies have reported encouraging survival rates using mainly venovenous ecmo in adults with ards [ ] [ ] [ ] [ ] [ ] [ ] [ ] . recently, an ecmo-based management protocol for selected ards patients transferred to a referral center was shown to improve -month disability-free survival [ , ] . however, owing to recent advances in the management of ards [ , ] , ecmo remains a salvage therapy in a limited number of patients with life-threatening hypoxemia or respiratory acidosis [ ] . moreover, because of its additional costs and the need for trained expertise [ , ] , a rational allocation of this limited resource is critical, and indications must be further explored. ecmo centers have developed and have long been associated with mobile units that retrieve patients from distant hospitals immediately after cannulation [ , ] . approximately half of the patients treated with ecmo for ards are cannulated in distant hospitals and transported on ecmo [ , , ] . for these patients, the decision to initiate ecmo is often made by phone and is based on the severity of respiratory failure, which is often evaluated by blood gas results or the lung injury score [ , ] . although some patients do not present with other organ failures, most of them present with septic shock and associated organ dysfunction. because they may contribute significantly to ecmo outcomes, an understanding of the impact of preexisting organ dysfunction on ecmo-associated mortality is helpful in modifying the current strategies of ecmo in the resuscitation of these high-risk patients [ ] . in the present study, we evaluated early prognostic factors in ards patients treated with ecmo in distant hospitals by our mobile team and brought to our center during a -year period. the goal was to establish simple decision rules that could aid the clinician in the decision regarding whether to treat patients with ecmo. marseille north hospital is a general acute-care, university hospital. it is a regional referral center for the treatment of severe respiratory infections. we established an ecmobased protocol in autumn that included a mobile unit that could initiate ecmo in referring hospitals of our region before transfer to our center [ , ] . we prospectively included all consecutive adult patients treated with ecmo in distant hospitals (a , -km region) by our mobile team and immediately brought to our center between october and march . only patients with ards were included. patients treated with ecmo as a bridge to or following lung transplantation or any surgery were not included. the protocol was approved by the local research ethics committee, who waived the need for informed consent, according to french legislation. referring hospitals were informed twice a year of ecmo criteria. the indication was discussed with one of three referees from our center who were contactable / through a hotline. a standardized form including ventilatory and blood gas parameters and sequential organ failure assessment (sofa) score parameters was prospectively completed. before consideration for ecmo, patients were all sedated using continuous neuromuscular blockade [ ] and ventilated with volume-controlled ventilation using a tidal volume (vt) of - ml/kg of predicted body weight. ecmo therapy was indicated if patients presented a pao to fio ratio of less than mmhg for at least h under an fio of and a peep level adjusted to obtain a plateau pressure (pplat) of cmh o, a pao to fio ratio of less than mmhg associated with a pplat value greater than cmh o, or respiratory acidosis with ph less than . despite a respiratory rate greater than /min. absolute contraindications included the following: any contraindication to heparin treatment, a chronic disease expected to be fatal within years, a sofa score greater than , and age over years. the sofa score [ ] was always precisely calculated before ecmo consideration. when feasible in the referring hospital, prone positioning was systematically performed before considering ecmo. relative contraindications were body mass index (bmi) greater than kg/m and duration of ards greater than days. venovenous ecmo was instituted using surgical cannulation, usually in a femoral-jugular configuration. echocardiography was performed in all patients before cannulation and each day under ecmo. this procedure enabled venoarterial cannulation to be performed initially or later in patients presenting with left heart failure on the basis of echocardiography, defined as a less than % left ventricular ejection fraction. we used centrifugal pumps (bio-console ; medtronic perfusion systems, minneapolis, mn, usa) with a flow of - l/min in all patients. circuits were heparin-coated and composed of quadrox d with bioline coating oxygenators (maquet, hirrlingen, germany), - fr cannulae (edwards lifesciences, irvine, ca, usa), and intersept polyvinyl chloride (pvc) class vi tubing (medtronic). initial ventilator settings were as follows: pplat, - cmh o; peep, - cmh o; respiratory rate, - breaths/min; and fio adjusted to obtain an arterial o saturation of - %, whereas the fio was set at on the oxygenator. the patients were transferred to our icu immediately after ecmo initiation by a team comprising one physician from our icu, the cardiac surgeon who cannulated the patient, and a perfusionist. continuous heparin infusion maintained the activated partial thromboplastin time (aptt) at - s. the triggering limits for transfusion were /ml for platelets and g/dl for hemoglobin. ecmo was continued until lung recovery or until irreversible multiorgan failure leading to death. patients were weaned from venovenous ecmo when the following criteria were met: pao to fio ratio greater than mmhg with peep less than cmh o, pplat less than cmh o with a vt of - ml/kg, fio of . on ecmo, blood flow of l/min, and gas flow of l/min. prospectively collected data included demographic data; presence of identified risk factors for ards and major co-morbidities; respiratory and hemodynamic parameters at admission, before ecmo initiation, and throughout ards evolution; duration of ecmo and of mechanical ventilation; complications; and outcome. icu and hospital mortality were recorded. the severity of the illness was assessed based on the simplified acute physiology score (saps) ii [ ] at icu admission and the sofa [ ] score before ecmo initiation and at days , , and of ecmo. the neurological score was calculated on the basis of the glasgow coma scale just before intubation. biological parameters were obtained in the h preceding cannulation for all patients. the number of ecmo-free days at day was defined as the number of days alive and free from ecmo at this time point. descriptive statistics included percentages for categorical variables and medians and interquartile ranges (iqrs) for continuous variables. comparisons were made using either the chi-square test or the fisher exact test for categorical variables and the student's t test or mann-whitney u test for continuous variables, according to their distribution. parameters significantly associated with hospital mortality on the basis of univariate analysis (p \ . ) were introduced into a logistic regression analysis. the final model expressed the odds ratios (or) and % confidence intervals (ci). to derive a simple and practical score to predict hospital mortality, we combined the logistic regression and the recursive partitioning analysis (rpa) [ , ] conducted using the rpart routine in r software [ ] . briefly, rpa accepts predictor and response values as the inputs. as the output, this function generates a decision tree using a recursive partitioning algorithm. each partitioning step selects the tree-branching criterion based on the predictor variables that will split the parent data set into two daughter data sets, with the daughter sets being as ''pure'' (homogeneous) as possible as approximated according to a heuristic. here, purity is measured with the gini statistic with respect to the response variable, such that the more homogeneous a daughter set, the higher the purity. partition steps are repeated, adding branches to the tree, until the subgroups reach a minimum size or until no improvement can be obtained. firstly, the significant variables in the multivariate logistic regression were selected into an rpa to build a decision tree. then the optimal cutoff in the tree associated with each variable was used to transform the continuous variables into categorical variables (named partial scoreps i ). with the aim to be as intuitive as possible, the score was constructed to give a result between and where is a lower risk of hospital mortality and a higher risk. the score can be calculated with the following formula: score = p ps i , where ps i is the partial score assigned to each categorical variable. the discriminative performance of the score was evaluated with a receiver operating characteristics (roc) curve and quantified by calculating the area under the curve and % ci. the best cutoff value was identified as the point with the highest sensitivity and specificity (youden index: se ? sp - ). lastly, kaplan-meier survival analysis was used to estimate the probability of survival after ecmo initiation for groups under and over the best cutoff value of the score. the log-rank test was used. statistical analysis was performed using the spss statistics software. during the study period, the referee from our center was contacted for consideration for ecmo by a referring hospital for patients with ards ( fig. ). among them, patients did not meet criteria for ecmo and were not referred and consecutive patients treated with ecmo were included. six of them had been included in a previous cohort study [ ] . patients' demographic characteristics are provided in table . no patient had a history of chronic heart, renal, or respiratory insufficiency. the main cause of ards was documented as communityacquired bacterial pneumonia (n = ). twenty patients presented with influenza pneumonia, of whom had been treated in the first half of the study period. the median (interquartile range) time between contact from the referring hospital and patient cannulation was ( - ) h; transfer to our center occurred within ( - ) h. no serious complications (including vascular or chest tube displacement, ecmo malfunction, cardiac arrest, or death) occurred during transport by our mobile unit. for venovenous ecmo, femoral-jugular vein cannulation was performed in patients, and femoral-femoral cannulation was performed in patients. femoral-femoral cannulation was performed in the eight patients treated with venoarterial ecmo. in all cases, venoarterial ecmo was used for left heart failure and severe shock complicating ards-associated disease. prior to ecmo, all patients had refractory hypoxemia, had a paco greater than mmhg, and had an arterial ph less than . . forty-eight patients died in the icu or at the hospital ( %). causes of death were multiorgan failure frequently associated with refractory hypoxemia (n = ); hemorrhagic complications secondary to cannulation (n = ); and intracerebral hemorrhage (n = ). forty-two nonsurvivors died during therapy after a median (range) of ( - ) days of ecmo, and of them died after successful ecmo weaning after a median (range) of ( - ) days of ecmo. survivors had a median (range) duration of ecmo therapy of ( - ) days and were mechanically ventilated for a median (interquartile range) duration of ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days. after univariate analysis, factors potentially collected before ecmo that were associated with hospital mortality were age, sofa score, lactate level, and a diagnosis of influenza pneumonia ( table ). saps ii was not considered for multivariate analysis because it could not constantly be obtained at this time and because sofa score is easier to use at the bedside. age, sofa score, and a diagnosis of influenza pneumonia were introduced into the logistic regression analysis, which showed that these three parameters were independently associated with hospital mortality. mortality increased with age [or . , ci ( . ; . ), p = . ] and sofa score [or . , ci ( . ; . ), p = . ] whereas a diagnosis of influenza pneumonia was associated with a lower risk of death [or . , ci ( . ; . ), p = . ]. lactate level was not introduced into the multivariate analysis because it was not available for all patients in the h before considering ecmo. the distribution of sofa subscores just before ecmo is presented in fig. . hemodynamic and liver scores were higher in nonsurvivors (p = . and p = . , respectively). the score developed after transforming continuous into categorical variables is displayed in table . the optimal cutoff for the score was identified as . . finally, the probability of hospital mortality following ecmo initiation was % in the - score class (n = ) and % in the - score class (n = ) ( fig. ; p \ . ). the area under the roc curve of the performance of this scoring system was . , ic [ . ; . ], p \ . . during ecmo therapy, patients were treated with high-frequency oscillatory ventilation, with prone positioning, and with corticosteroids for ards ( table ) . sofa scores at day , , or of ecmo were higher in hospital nonsurvivors than in survivors. renal replacement therapy during ecmo was used more frequently in nonsurvivors than in survivors. hemorrhagic complications occurred in patients ( %) under ecmo. major hemorrhagic complications were retroperitoneal hematoma secondary to cannulation (n = ), intracerebral hemorrhage (n = ), and hemothorax due to fibrinolysis requiring ecmo weaning (n = ). other hemorrhagic complications were limited or moderate respiratory tract hemorrhage (n = ), epistaxis requiring nasal packing (n = ), and limited hemorrhage at cannulation sites (n = ). while under ecmo, patients were transfused with a median (iqr) of ( - ) units of red blood cells [ ( - ) u/day], ( - ) units of frozen plasma, and ( - ) unit of platelets. in eight cases, membrane exchange was required during ecmo therapy because of acute hemolysis. the results of the present study show that age, sofa score calculated in the h before ecmo, and a diagnosis of influenza pneumonia are independently associated with hospital mortality in ards patients retrieved under ecmo from distant hospitals and brought to our ecmo fig. distribution of sofa score and subscores before ecmo in survivors (white bars) and in nonsurvivors (black bars). the neurological score was and the respiratory score was in all patients center. these simple criteria can be included in a simple score to help clinicians make decisions regarding whether to treat patients with ecmo. our study is the first to analyze prognostic factors prior to ecmo in patients who have all been cannulated in distant hospitals. this population is likely to represent the majority of patients considered for ecmo in the future. those patients are often considered for ecmo under rescue conditions, and the decision to initiate ecmo is often difficult. our results show that simple criteria can be useful in predicting the prognosis in those patients despite the rapid evolution of their organ dysfunctions. another strength of the present study is that it only includes patients with ards. previous studies have frequently mixed patients with ards and cardiogenic shock [ , , [ ] [ ] [ ] , whereas these diseases are likely to affect different populations and to have different prognostic factors. most studies have shown that ecmo can be applied with encouraging survival rates [ ] [ ] [ ] [ ] [ ] [ ] [ ] . although the % mortality rate found in the present study is in agreement with most other studies, some studies have reported lower rates. in the cesar trial [ ] , % of patients treated with ecmo survived. of note, most of our patients had pneumonia with severe septic shock requiring vasopressors, and half of them required renal replacement therapy during the icu stay, which has been shown to have an important prognostic impact in ecmo patients [ , ] . moreover, mortality rate is most likely largely influenced by indications and contraindications defined by each center. in the present study, indications were quite liberal regarding the evolution of organ dysfunctions, making it possible to accurately evaluate their prognostic impact. to date, decision criteria given for ecmo initiation in guidelines and studies are still undefined. nevertheless, a recent study [ ] showed that the application of new criteria based on extracorporeal life support organization (elso) guidelines [ ] resulted in a higher mortality compared with previous criteria used at the same center, suggesting a strong influence of these criteria on the reported outcomes. studies, some with large numbers of patients, have identified early prognostic factors in patients treated with ecmo [ , , , , , , , ] . the analysis of the elso multicenter database has notably identified age as a pre-ecmo factor associated with prognosis in patients with acute respiratory failure [ ] . for this reason, only a few patients over years of age are treated with ecmo [ , , ] . recently, schmidt et al. [ ] reported that age over years was associated with a higher mortality. in the present study, we also observed that patients less than years old had a markedly better prognosis and that outcome was independent of other organ dysfunctions in those very young patients. this important finding suggests that ecmo should not be contraindicated on the basis of organ dysfunction in young patients. we found that the sofa score before ecmo was associated with mortality. the sofa score is simple to calculate and has been validated as a marker of organ dysfunction and of mortality in large multicenter studies in different patient populations [ ] . in a cohort of patients treated with ecmo for respiratory or heart failure, wu et al. [ ] suggested the prognostic value of sofa calculated before ecmo. recently, lindskov et al. [ ] showed that the sofa score calculated at day after ecmo initiation was predictive of death. in this latter study, a sofa score of or less was associated with % survival. in the study by wu et al. [ ] , the mean sofa score before ecmo was ± in ards patients, whereas it was ± in our study. however, as in the study by lindskov et al. [ ] , a higher score was associated with higher hospital mortality sofa sequential organ failure assessment fig. kaplan-meier estimates of cumulative probabilities of survival for patients with pre-ecmo score classes - (n = ), and - (n = ). ecmo extracorporeal membrane oxygenation sofa was not calculated in the same way as in the present study. notably, the glasgow coma scale score was set arbitrarily to points. no patient presented with impaired consciousness at the time of sedation in our study, resulting in a -point neurological score in all patients. pappalardo et al. [ ] proposed a prognostic score in patients with h n -associated ards treated with ecmo that was based on biological and clinical data similar to the data used to determine the sofa score. more recently, schmidt et al. [ ] proposed a prognostic score in ards patients treated with ecmo in which sofa had a quite similar weight to that in the present study. we found that a diagnosis of influenza-associated ards was associated with a better prognosis. our % mortality rate is in agreement with recent studies in patients with influenza h n -associated ards treated with ecmo [ , ] . our results also confirm those of previous observational studies suggesting that patients treated with ecmo for influenza pneumonia have a lower risk of death than patients presenting with other causes of ards [ ] . however, no study had previously clearly shown a protective effect of influenza in ecmo patients. unfortunately, the diagnosis of influenza is inconsistently confirmed but rather suspected at the time the ecmo decision is made. therefore, this parameter cannot be taken into account in all patients when making ecmo decisions. of note, all patients in our study who had confirmed influenza had been suspected of having influenza at ecmo initiation, and only three patients with suspected influenza were not confirmed. some studies have shown that the duration of mechanical ventilation before ecmo is associated with mortality [ , , , ] . in our study, the duration of mechanical ventilation prior to ecmo was not longer in nonsurvivors. however, it is notable that our duration of ventilation before ecmo was short. the analysis of the elso database showed that the duration of mechanical ventilation was no longer associated with mortality in the most recently treated patients [ ] , whereas the number of patients treated after days of mechanical ventilation decreased with time. further studies are necessary to clearly address this question. the present study is a single-center study, which could limit the translation of our results to other centers. however, our population has been stringently selected on the basis of predefined criteria and has benefited from protocolized treatments, including medical and technical maintenance of ecmo support. it is notable that the predefined indications that we used for ecmo based on gas exchange and ventilator pressure are not universally standardized and remain an important topic of discussion. in ards patients treated mainly with venovenous ecmo and retrieved after cannulation from referring hospitals, age, sofa score just before considering ecmo, and a diagnosis of influenza pneumonia can be used to aid the clinician in the decision about whether to initiate ecmo. prognosis is much less dependent on organ dysfunction in young patients. a diagnosis of influenza-associated ards is associated with a lower mortality rate. extracorporeal membrane oxygenation for respiratory failure in adults extracorporeal membrane oxygenation for influenza a(h n ) acute respiratory distress syndrome extracorporeal life support for severe acute respiratory distress syndrome in adults extracorporeal membrane oxygenation for severe influenza a (h n ) acute respiratory distress syndrome: a prospective observational comparative study extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-centre database high survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange support timedependent outcome analysis for venovenous extracorporeal membrane oxygenation efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza a(h n ) neuromuscular blockers in early acute respiratory distress syndrome prone positioning in severe acute respiratory distress syndrome what is the niche for extracorporeal membrane oxygenation in severe acute respiratory distress syndrome? extracorporeal life support organization ( ) elso guidelines for ecmo centers increased extracorporeal membrane oxygenation center case volume is associated with improved extracorporeal membrane oxygenation survival among pediatric patients interhospital transport of the patient on extracorporeal cardiopulmonary support inter-hospital transportation of patients with severe acute respiratory failure on extracorporeal membrane oxygenation-national and international experience extracorporeal membrane oxygenation in adult patients with severe acute respiratory failure predicting mortality risk in patients undergoing venovenous ecmo for ards due to influenza a (h n ) pneumonia: the ecmonet score contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era an expanded definition of the adult respiratory distress syndrome acute respiratory distress syndrome following h n virus pandemic: when ecmo come to the patient bedside the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine a new simplified acute physiology score (saps ii) based on a european/north american multicenter study an introduction to recursive partitioning using the rpart routines. mayo foundation, rochester evaluation of outcome scoring systems for patients on extracorporeal membrane oxygenation impact of preexisting organ dysfunction on extracorporeal life support for nonpostcardiotomy cardiopulmonary failure predictors of mortality in patients successfully weaned from extracorporeal membrane oxygenation prognosis of patients on extracorporeal membrane oxygenation: the impact of acute kidney injury on mortality is it possible to predict outcome in pulmonary ecmo? analysis of preoperative risk factors extracorporeal membrane oxygenation in acute adult respiratory distress syndrome mortality is directly related to the duration of mechanical ventilation before the initiation of extracorporeal life support for severe respiratory failure the preserve mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome key: cord- -xehwgzdn authors: pilarczyk, k.; trummer, g.; jakob, h.-g.; dusse, f.; marggraf, g. title: extrakorporale herz- und lungenersatzverfahren: „extracorporeal membrane oxygenation“, „extracorporeal life support“ und „pumpless extracorporeal lung assist“ date: - - journal: z herz thorax gefasschir doi: . /s - - - sha: doc_id: cord_uid: xehwgzdn the use of extracorporeal support systems in cardiac and/or pulmonary failure is an established treatment option. although scientific evidence is limited there is an increasing amount of data from individual studies, e.g. conventional ventilation or ecmo for severe adult respiratory failure (cesar) trial , suggesting that extracorporeal membrane oxygenation (ecmo) as a veno-venous pump-driven system is a life-saving procedure in severe respiratory failure. initially established as a rescue option for postcardiotomy cardiac failure extracorporeal life support (ecls) as a pump-driven veno-arterial cardiovascular support system is increasingly being used in cardiogenic shock after myocardial infarction, as bridging to transplantation or as part of extended cardiopulmonary resuscitation. the pumpless extracorporeal lung assist (pecla) as an arterio-venous pumpless system is technically easier to handle but only ensures sufficient decarboxylation and not oxygenation. therefore, this method is mainly applied in primarily hypercapnic respiratory failure to allow lung protective ventilation. enormous technical improvements, e.g. extreme miniaturization of the extracorporeal assist devices must not obscure the fact that this therapeutic option represents an invasive procedure frequently associated with major complications. with this in mind a widespread use of this technology cannot be recommended and the use of extracorporeal systems should be restricted to centers with high levels of expertise and experience. "extracorporeal membrane oxygenation", "extracorporeal life support" und "pumpless extracorporeal lung assist" begriffsbestimmungen da es viele verschiedene begriffe rund um das thema temporäre lungen-und herz-kreislauf-ersatzverfahren gibt und diese häufig irreführend sowie uneinheitlich sind, hat die deutsche interdisziplinäre vereinigung für intensivmedizin (divi) sich auf die im folgenden ausgeführten empfehlungen geeinigt ( [ ] ; . abb. ): als "extracorporeal membrane oxygenation" (ecmo) wird die venovenös angeschlossene, pumpenbetriebene lungenunterstützungstherapie mit oxygenator bezeichnet. sie zeichnet sich durch oxygenierung sowie decarboxylierung aus dem venösen blut aus und wird zur therapie von konservativ nichtbeherrschbarem, hpyoxämischem lungenversagen eingesetzt. eine herz-kreislauf-unterstützung ist mit diesem verfahren aufgrund der kanülierung nicht möglich. abzugrenzen davon ist die "pumpless extracorporeal lung assist" (pecla), ein arteriovenös angeschlossenes, nichtpumpenbetriebenes lungenunterstützungsystem mit einem "low-resistance"-oxygenator, das aufgrund der arteriovenösen blutdruckdifferenz und damit abhängig vom herzzeitvolumen (hzv) des patienten eine suffiziente decarboxylierung, jedoch keine ausreichende oxygenierung gewährleistet. somit wird dieses system nahezu ausschließlich beim primär hyperkapnischen lungenversagen eingesetzt. als "extracorporeal life support" (ecls) -früher u. a. als venoarterielle ecmo bezeichnet -wird ein venoarteriell angeschlossenes pumpenbetriebenes herz-kreislauf-unterstützungsystem bezeichnet, das nicht nur den gasaustausch gewährleistet, sondern nahezu das gesamte hzv des patienten übernehmen kann. zentrifugalpumpen arbeiten nichtokklusiv. daher kann es bei stehender pumpe oder einer zu geringen drehzahl beim ecls-system zum rückfluss vom arteriellen in den venösen schenkel kommen. aus diesem grund müssen die schläuche bei stehender pumpe immer abgeklemmt werden. der vorteil der zentrifugalpumpe liegt in der geringeren blutschädigung. in der regel werden ecmo-systeme nichtpulsatil betrieben, zentrifugalpumpen mit impellern können jedoch auch pulsatil betrieben werden. die verfügbaren systeme sind alle kompakt und mit einem akku ausgestattet, sodass sie für transporte geeignet, aber noch nicht alle für alle arten des transports zugelassen sind. die unterschiede der einzelnen systeme betreffen insbesondere ihre beschichtungen: während einige systeme bioaktive heparinbeschichtungen besit-zen, sind andere biopassiv mit einer "physio" (phosphorylcholin) beschichtet. schlüsselwörter "acute respiratory distress syndrome" · "acute lung injury" · oxygenierung · decarboxylierung · kardiopulmonale reanimation extracorporeal heart and lung replacement procedures. the use of extracorporeal support systems in cardiac and/or pulmonary failure is an established treatment option. although scientific evidence is limited there is an increasing amount of data from individual studies, e.g. conventional ventilation or ecmo for severe adult respiratory failure (cesar) trial , suggesting that extracorporeal membrane oxygenation (ecmo) as a veno-venous pump-driven system is a life-saving procedure in severe respiratory failure. initially established as a rescue option for postcardiotomy cardiac failure extracorporeal life support (ecls) as a pump-driven veno-arterial cardiovascular support system is increasingly being used in cardiogenic shock after myocardial infarction, as bridging to transplantation or as part of extended cardiopulmonary resuscitation. the pumpless extracorporeal lung assist (pecla) as an arterio-venous pumpless system is technically easier to handle but only ensures sufficient decarboxylation and not oxygenation. therefore, this method is mainly applied in primarily hypercapnic respiratory failure to allow lung protective ventilation. enormous technical improvements, e.g. extreme miniaturization of the extracorporeal assist devices must not obscure the fact that this therapeutic option represents an invasive procedure frequently associated with major complications. with this in mind a widespread use of this technology cannot be recommended and the use of extracorporeal systems should be restricted to centers with high levels of expertise and experience. acute respiratory distress syndrome · acute lung injury · oxygenation · decarboxylation · cardiopulmonary resuscitation primärziel der beatmung unter ecmo-therapie ist die vermeidung einer weiteren "ventilatorassoziierten lungenschädigung" ("ventilator-associated lung injury", vali). daher sollte eine maximal-lungenprotektive beatmung durchgeführt werden. zugleich sollte eine zeitnahe spontaneisierung ggf. mit frühzeitiger tracheotomie des patienten erfolgen, um unerwünschte effekte einer prolongierten invasiven beatmung [ventilatorassoziierte pneumonie (vap), hypotrophie der atemhilfsmuskulatur etc.] zu reduzieren. auch wenn in den letzten jahren auf dem gebiet der extrakorporalen systeme ei-ne rasante technische entwicklung stattgefunden hat, sind komplikationen während der ecmo-therapie nicht selten. eine Übersicht über art und häufigkeit von komplikationen unter ecmo-therapie gibt . tab. (http://www.eslonet.com). der aufbau eines "extracorporeal life support" (ecls) entspricht prinzipiell dem der ecmo; lediglich die kanülierung unterscheidet sich: bei einer ecls als herzoder herz-lungen-ersatz wird venöses blut aus der v. cava inferior entnommen und arteriell zurückgeführt. die ecls kann sowohl zentral, d. h. im bereich der thorakalen aorta und des rechten vorhofs, als auch peripher im bereich der a. femoralis oder a. subclavia angeschlossen werden. insgesamt existieren kanülierungskonfigurationen, die durch spezifische hämodynamische verhältnisse und komplikationen charakterisiert sind. so kann es je nach art der kanülierung zu einer mehr oder weniger stark ausgeprägten mischung von sauerstoffreichem und -armem blut in der oberen körperhälfte kommen. venöser abfluss über die v. femoralis, arterieller zufluss peripher über die a. femoralis. das einbringen einer großlumigen kanüle in das periphere arterielle gefäßsystem kann zu perfusionsstörungen distal der kanüle führen. zur prophy-laxe kann distal der arteriellen ecls-kanüle eine beinperfusionskanüle ( - f) in seldinger-technik eingebracht werden. alternativ besteht die möglichkeit, den peripheren arteriellen gefäßzugang chirurgisch mithilfe der aufnaht einer gefäßprothese (meist mm) herzustellen. das linke herz sollte unter ecls-therapie zwar weitgehend entlastet werden, dennoch leicht auswerfen, um thrombenbildungen an der ansonsten verschlossenen aortenklappe zu vermeiden und um den linken ventrikel zu entleeren. je nach ausmaß der linksventrikulären auswurfleistung resultiert somit eine unterschiedlich stark ausgeprägte mischperfusion der körpers (. abb. ): auch bei deutlich eingeschränkter eigener kardialer auswurfleistung findet unter ecls-therapie die koronardurchblutung hauptsächlich über das linksventrikulär ausgeworfene blut statt. bei zunehmender auswurfleistung werden die gesamte obere körperhälfte über das ausgeworfene blut, die untere körperhälfte über das retrograd von der ecls zurückgeführte blut perfundiert. im fall eines begleitenden lungenversagens ist das vom herzen ausgeworfene blut schlecht oxygeniert, sodass sowohl die koronargefäße -mit konsekutiver myokardialer hypoxie -als auch ggf. die oberen extremitäten und der kopf des patienten einer sauerstoffunterversorgung unterliegen ("harlekin-phänomen"). dies kann dazu führen, dass zwischen rechtem und linkem arm sowie den unteren extremitäten die arteriellen sauerstoff-und kohlendioxidpartialdrücke und auch die arterielle sauerstoffsättigung stark differieren können. da der ort des höchsten mischblutanteils aufgrund der anatomischen situation der rechte arm ist, sollten sowohl das monitoring der sauerstoffsättigung als auch die blutgasentnahme an dieser stelle erfolgen, um eine lokale hypoxämie frühzeitig detektieren zu können. des weiteren kann es -insbesondere bei einer insuffizienz der aortenklappe -zu einer massiven volumenbelastung des linken ventrikels mit linksventrikulärer distension kommen. in diesem fall muss ein "vent" im linken ventrikel für entlastung sorgen, der das system allerdings verkompliziert und es anfälliger für u m s c h l a g p u n k t e c l s -f l u s s / l v -p u l s a t io n abb. hämodynamische bedingungen bei zunehmender kardialer pumpfunktion unter "extracorporeal-life-support"(ecls)-therapie bei femorofemoraler kanülierung. lv linksventrikulär luftembolien macht. alternativ kann eine vorhofseptostomie erfolgen [ ] . im gegensatz zur ecmo hat sich das verfahren der ecls außerhalb der herzchirurgie im rahmen eines postkardiotomielow-output-syndroms erst in den letzten jahren etabliert. daher existieren bisher kaum empfehlungen zum einsatz der ecls [ ] . im allgemeinen ist die ecls-implantation bei patienten mit therapierefraktärem kardiogenem schock zu erwägen, wenn diese trotz maximaler konservativer therapie einschließlich volumen-, vasopressor-, inotropikagabe sowie intraaortaler-ballonpumpen(iabp)-implantation keine ausreichende systemische perfusion aufbauen [ ] . des weiteren ist die ecls unter gewissen umständen im rahmen einer erweiterten kardio-pulmonalen reanimation ("cardiopulmonary resuscitation", cpr) zu erwägen. die entscheidung zur ecls-implantation muss immer im team und individuell von fall zu fall getroffen werden. dabei müssen v. a. patientenalter, prognose des patienten, begleiterkrankungen, ziel der ecls-therapie, neurologischer status und bereits vorliegende endorganschäden (multiorganversagen?) berücksichtigt werden. folgende erkrankungen gelten als grundlage der ecls-implantation: f "post-perfusion low-cardiac output" bzw. "weaning"-versagen nach extrakorporaler zirkulation, f akute exazerbation einer chronischen herzinsuffizienz, f akute massive lungenemboli, f akutes kardiales versagen nach intoxikation, f kühlung von patienten nach herz-kreislauf-stillstand, f kardiogener schock bei akutem myokardinfarkt und f akute transplantatabstoßung. da es sich bei der ecls nicht um eine dauerhafte therapieoption, sondern um eine Überbrückungsmaßnahme handelt, kann die ecls-therapie aufgrund ihrer zielsetzung, wie folgt, klassifiziert werden: f "bridge to recovery": Überbrückung bis zur erholung der myokardialen funktion, v. a. bei myokarditispatienten. f "bridge to decision": in der akutsituation ist die entscheidung für eine weiterführende, eskalierende therapie oft schwierig, z. b. bei unklarer neurologischer situation nach reanimation. die ecls bietet die möglichkeit der stabilisierung in der akutphase, um zeit für die weitere therapieplanung [z. b. "left-ventricle-assistent-device"(lvad)-implantation] zu gewinnen. f "bridge to bridge": die Überbrückung zur implantation eines kardialen assist device [lvad, rcad, bvad), um dann eine herztransplantation anzustreben. f "bridge to transplantation": Überbrückung zur herztransplantation. in den aktuellen nationalen und internationalen leitlinien zur cpr wird die ecls als bevorzugte methode zur aktiven internen wiedererwärmung bei hypothermen patienten mit atem-und herz-kreislauf-stillstand sowie patienten nach intoxikation mit kardiodepressiven substanzen und konsekutivem herz-kreislauf-versagen empfohlen [ ] . zahlreiche studien belegen jedoch, dass der einsatz eines ecls-systems unter cpr prinzipiell bei jeder potenziell kurativ behandelbaren grundkrankheit zu überlegen ist. anhand kleiner fallzahlen ist eine Überlebensrate nach herz-kreislauf-stillstand und cpr durch den ecls-einsatz von % beschrieben, bei patienten, die sonst keine therapiemöglichkeit mehr gehabt hätten [ ] . andere untersuchungen berichten von einer krankenhausüberlebensrate nach einsatz eines ecls-systems bei cpr von - % [ ] . eine prospektive, randomisierte studie zum ecls bei "outof-hospital cardiac arrest" ist in planung (prague ohca study). möglichkeit und sinnhaftigkeit der ecls-implantation während der cpr bleiben individuell im einzelfall abzuwägen und hängen von der prognose des patienten sowie dauer, art und grund der cpr ab. die ecls-implantation erfordert einen hohen logistischen aufwand sowie ein ecls-team im "standby" ( / ). ein möglicher algorithmus zur evaluation von patienten unter cpr hinsichtlich der indikation zur ecls-implantation ist in . abb. zu sehen. ein ausschlusskriterium ist der hypoxische herz-kreislauf-stillstand. moderne ecmo-/ecls-systeme sind leicht zu implantieren, hoch effektiv und transportabel. dennoch dürfen rasante entscheidend für den erfolg der pec-la-therapie scheint, ähnlich wie bei der ecmo-therapie, der frühzeitige einsatz zu sein, um der lungenschädigung durch eine aggressive beatmung vorzubeugen: so ist dem "ila-registry" zufolge die Überlebensrate bei patienten mit "chronic obstructive pulmonary disease" (copd) im fall einer frühzeitigen pec-la-implantation (< h nach respiratorischer acidose, ph < , ) mit % signifikant besser als bei patienten mit verspäteter ila-therapie (http://www.novalung. com). prospektiv-randomisierte studien zum einsatz der pecla existieren nicht. die mortalität lag in den bisher publizierten fallserien mit % ( von patienten) unter der erwarteten sterblichkeit. in allen studien konnte die suffiziente decarboxylierung mit konsekutiver deeskalation der mechanischen beatmung erreicht werden. die inzidenz von lokalen komplikationen an der arteriellen kanülierungsstelle konnte im zeitraum von bis von , auf , % gesenkt werden; es traten keine pecla-assozierten todesfälle auf [ ] . aufgrund ständiger technischer weiterentwicklung, insbesondere im bereich der systemminiaturisierung, sind die weitere zunahme der implantationszahlen und auch die ausweitung auf weitere indikationsgebiete im bereich der kurz-und längerfristigen herz-/lungenunterstützungssysteme zu erwarten. im bereich der ecls-therapie hat der bereits stattgefundene wandel der lvad-therapie weg vom "bridging to transplant" hin zur "destination"-therapie zu einer breiteren anwendung an patienten, die keine transplantationskandiaten sind, diagnostik und interventionelle therapie köln: deutscher Ärzte-verlag , s., abb., (isbn - - - - ) , . eur mit dem herzkatheter-manual von raimund erbel, björn pflicht, philipp kahlert und thomas konorza aus essen wurde ein buch aufgelegt, welches sich nach -jähriger entwicklungs-und reifungsphase ohne weiteres in die reihe der großen lehrbücher der invasiven kardiologie einfügt. das buch beginnt mit einer aufarbeitung der durchaus nicht immer geradlinigen geschichte der interventionellen kardiologie, welche durch das geleitwort von professor jürgen meyer, einem der pioniere der ptca, eingerahmt wird. schon beim durchblättern des seiten starken lehrbuchs erkennt man die reize dieses werks. die autoren haben auf basis einer langen beruflichen und praktischen erfahrung die zentralen aspekte der invasiven kardiologie im herzkatheterlabor herausgearbeitet und didaktisch hervorragend aufbereitet. mit einer beeindruckenden anzahl an grafiken, bildern und diagrammen wird einem das komplette spektrum der diag nostischen und therapeutischen verfahren der interventionellen kardiologie veranschaulicht. angefangen bei den zugrunde liegenden pathologien werden krankheitsbilder, diagnostik und die hoch technisierten, tagesaktuellen therapieverfahren erläutert. von der instabilen angina pectoris über den infarkt und die aortendissektion bis hin zu neuesten interventionellen verfahren, wie der transfemoralen und transapikalen aortenklappenimplantation, sind alle bereiche vertreten, mit denen man sich als interventionell tätiger kardiologe konfrontiert sehen könnte. zusätzlich bekommt man praxisbezogene tipps und tricks an die hand, sowie einleuchtende handlungsleitfäden, die für das eigene katheterlabor technisch und organisatorisch umgesetzt werden können. auf dem weg zum interventionellen kardiologen kann das buch ein wertvoller begleiter sein. allen aktuellen leitlinien, studienprotokollen und "standard operating procedures" zum buchbesprechungen trotz schaffen es die autoren dank des lebendigen schreibstils, die neugier des lesers immer wieder neu zu entfachen. einzig die beigefügte cd mag ein wenig enttäuschen, wenn man das ein oder andere video einer intervention erwartet hat. der datenträger liefert "lediglich" das im herzinfarktverbund essen verwendete material zur patienteninformation über das akute koronarsyndrom, seiner diagnose und der therapieverfahren sowie das handbuch mit den "standing orders" der essener katheterlabore. am ende stehen zwei dinge fest: es war eine freude, dieses werk rezensieren zu dürfen, und wer invasiv kardiologisch tätig sein möchte, dem sei dieses lehrbuch herzlich empfohlen. einteilung mechanischer herz-, lungen und/oder kreislaufunterstützungssysteme ambulatory veno-venous extracorporeal membrane oxygenation: innovation and pitfalls bedside exclusion of clinically significant recirculation volume during venovenous ecmo using conventional blood gas analyses extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database extracorporeal membrane oxygenation in severe acute respiratory failure. a randomized prospective study randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal co removal for adult respiratory distress syndrome efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for pandemic influenza a(h n ) induced acute respiratory distress syndrome. a cohort study and propensity-matched analysis the american-european consensus conference on ards. definitions, mechanisms, relevant outcomes, and clinical trial coordination acute respiratory distress syndrome: the berlin definition current approaches to the treatment of severe hypoxic respiratory insufficiency (acute lung injury; acute respiratory distress syndrome) evidence-based therapy of severe acute respiratory distress syndrome: an algorithm-guided approach percutaneous left-heart decompression during extracorporeal membrane oxygenation: an alternative to surgical and transeptal venting in adult patients position article for the use of extracorporeal life support in adult patients part : executive summary: international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations a -year experience with cardiopulmonary resuscitation using extracorporeal life support in non-postcardiotomy patients with cardiac arrest assessment of outcomes and differences between inand out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal life support société française d'anesthésie et de réanimation, société française de cardiologie, et al ( ) guidelines for indications for the use of extracorporeal life support in refractory cardiac arrest. french ministry of health a new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia pumpless extracorporeal interventional lung assist in patients with acute respiratory distress syndrome: a prospective pilot study geführt. darüber hinaus gibt es zunehmend bemühungen zur etablierung von netzwerken, um patienten im schwersten kardiogenen schock oder sogar im rahmen einer cpr auch jenseits des herzchirurgischen settings mit einer ecls zu versorgen und anschließend in ein zentrum der maximalversorung mit herzchirurgischer expertise zu verlegen. des weiteren gibt es erste positive berichte über den einsatz eines ecls in der therapie des septischen schocks; eine asiatische retrospektive observationsstudie wird voraussichtlich ende vorgestellt.die pecla hat sich in den letzten jahren weg vom rescue-verfahren beim schwersten hyperkapnischen lungenversagen hin zum tool zur vermeidung einer lungenschädigenden beatmung entwickelt. so wird dieses verfahren zunehmend beim wachen ansprechbaren patienten angewendet, um die endotracheale intubation mit all ihren negativen effekten zu vermeiden. Ähnliches lässt sich von der ecmo-therapie berichten: aufgrund des wissens um dies lungenschädigenden effekte einer aggressiven beatmung wird die indikation zur ecmo-therapie immer früher gestellt. eine prospektive randomisierte studie zum frühen einsatz der ecmo - - h nach diagnose eines schweren ards -befindet sich in der rekrutierungsphase (extracorporeal membrane oxygenation for severe acute respiratory distress syndrome, eolia).insbesondere die anwendung einer doppellumenkanüle ermöglicht den langzeiteinsatz in wachen und mobilen patienten, z. b. als bridging zur lungentransplantation. die ergebnisse einer prospektiven studie zur ecmo-therapie in wachen patienten vor lungentransplantation werden erwartet. zusammengefasst handelt es sich daher bei der extrakorporalen herz-und/oder lungenunterstützung um ein gebiet mit großem entwicklungspotenzial, das nicht nur zahlenmäßig immer mehr in den fokus der herzchirurgen und der intensivmediziner tritt. key: cord- - iwsvku authors: lindén, viveka; palmér, kenneth; reinhard, jarl; westman, reino; ehrén, henrik; granholm, tina; frenckner, björn title: high survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation date: - - journal: intensive care med doi: . /s sha: doc_id: cord_uid: iwsvku objectives: to evaluate the results of treatment of severe acute respiratory distress syndrome (ards) with extracorporeal membrane oxygenation (ecmo), minimal sedation, and pressure supported ventilation. design and setting: observational study in a tertiary referral center, intensive care unit, astrid lindgren children's hospital at karolinska hospital, stockholm, sweden. subjects and methods: seventeen adult patients with ards were treated with venovenous or venoarterial ecmo after failure of conventional therapy. the murray score of pulmonary injury averaged . ( . – . ) and the mean pao( )/fio( ) ratio was ( – ). a standard ecmo circuit with nonheparinized surfaces was used. the patients were minimally sedated and received pressure-supported ventilation. high inspiratory pressures were avoided and arterial saturation as low as % was accepted on venovenous bypass. results: in one patient a stable bypass could not be established. among the remaining patients survived (total survival rate %) after – days (mean ) on bypass. major surgical procedures were performed in several patients. the cause of death in the three nonsurvivors was intracranial complications leading to total cerebral infarction. conclusion: a high survival rate can be obtained in adult patients with severe ards using ecmo and pressure-supported ventilation with minimal sedation. surgical complications are amenable to surgical treatment during ecmo. bleeding problems can generally be controlled but require immediate and aggressive approach. it is difficult or impossible to decide when a lung disease is irreversible, and prolonged ecmo treatment may be successful even in the absence of any detectable lung function. abstract objectives: to evaluate the results of treatment of severe acute respiratory distress syndrome (ards) with extracorporeal membrane oxygenation (ecmo), minimal sedation, and pressure supported ventilation. design and setting: observational study in a tertiary referral center, intensive care unit, astrid lindgren children's hospital at karolinska hospital, stockholm, sweden. subjects and methods: seventeen adult patients with ards were treated with venovenous or venoarterial ecmo after failure of conventional therapy. the murray score of pulmonary injury averaged . ( . ± . ) and the mean pao /fio ratio was ( ± ). a standard ecmo circuit with nonheparinized surfaces was used. the patients were minimally sedated and received pressure-supported ventilation. high inspiratory pressures were avoided and arterial saturation as low as % was accepted on venovenous bypass. results: in one patient a stable bypass could not be established. among the remaining patients survived (total survival rate %) after ± days (mean ) on bypass. major surgical procedures were performed in several patients. the cause of death in the three nonsurvivors was intracranial complications leading to total cerebral infarction. conclusion: a high survival rate can be obtained in adult patients with severe ards using ecmo and pressure-supported ventilation with minimal sedation. surgical complications are amenable to surgical treatment during ecmo. bleeding problems can generally be controlled but require immediate and aggressive approach. it is difficult or impossible to decide when a lung disease is irreversible, and prolonged ecmo treatment may be successful even in the absence of any detectable lung function. and a high concentration of inspired oxygen may be mandatory but is harmful to the lungs and may cause further damage [ , , , ]. extracorporeal membrane oxygenation (ecmo) involves gas exchange through an extracorporeal oxygenator and provides oxygenation and carbon dioxide removal without interfering with the lungs. although initial results were disappointing [ , ] , encouraging reports have recently been published [ , , ]. our present ecmo program started in with neonatal patients. pediatric patients have been accepted since and in the program also opened for adult patients (a former program at karolinska institutet for adult patients had been closed a few years earlier [ ] ). the aim of this report was to analyze results from the first adult patients with ards treated with ecmo in our center. indications for ecmo patients were accepted for ecmo if there was an acute, reversible, life-threatening form of respiratory failure unresponsive to conventional therapy [ ] . the criteria for fast entry were: pao /fio ratio below mmhg and transpulmonary shunt higher than on fio above . for h, chest radiography with diffuse infiltrates in all quadrants. unresponsiveness to prone position, inhaled no, or high-frequency oscillatory ventilation (since ) and persistent hypercapnia were used as slow entry criteria. exclusion criteria were: age above years, advanced multiple organ failure, underlying severe disease, or severe immune suppression. a standard ecmo technique was used [ ] . in venoarterial (v-a) ecmo blood was drained from the right atrium via a cannula in the right internal jugular vein and returned to the right common carotid artery, which was ligated cranial to the cannula. in venovenous (v-v) ecmo blood was normally drained from the right atrium and returned to one femoral or external iliac vein, although the opposite direction was used on a few occasions. normally v-v ecmo was preferred, but if the patient was hemodynamically unstable or was to be transported on bypass, v-a ecmo was used [ ] . the blood was pumped with a stöckert roller pump through two membrane oxygenators ( . or . m ) and heat exchangers (avecor) in parallel. nonheparinized polyvinylchloride tubing was used except for the raceway, where supertygon was used. the standard ecmo cart was equipped with a battery backup, thus being mobile and useful for transports within the hospital. at the beginning of the series and in all cases of v-a bypass the cannulation was performed as an open surgical cut-down procedure. the last patients in the series on v-v bypass were cannulated using a percutaneous or a semipercutaneous technique. bypass was maintained at a rate necessary to provide adequate gas exchange or at a rate equal to the maximal venous return. the membrane lungs were ventilated with oxygen and co less than % at a flow of ± l/min. as soon as the patient was stable on bypass, ventilator settings were reduced to rest settings (approx. fio . , peak inspiratory pressure , positive end-expiratory pressure ± , rate ; siemens ). et tubes were avoided in order to decrease the need of sedation. patients, who were not tracheotomized, received a tracheostoma within a few days on ecmo to facilitate airway management. initially during the ecmo run when gas exchange over the lungs was minimal, arterial saturations as low as % had to be accepted when the patient was on v-v bypass. patients on v-v bypass were weaned to a flow rate of approx. l/min, after which the sweep gas was decreased and turned off several hours before decannulation. patients on v-a bypass were weaned to a flow rate of about . l/ min and kept on this low flow for several hours before decannulation. decannulation was performed with the patients only slightly sedated and under local anesthesia, when the patient had been cannulated by an open surgical procedure. cannulas inserted percutaneously or semipercutaneously were simply withdrawn without anesthesia and with a gentle pressure applied afterwards. no bridges were used in the circuit. anticoagulant therapy was kept between and s by a continuous heparin infusion. apart from standard blood chemistry, coagulation parameters (pk, activated partial thromboplastin time, fibrinogen, d-dimers, antithrombin iii, fibrin monomers) were analyzed daily. when there were signs of consumption coagulopathy, intravascular coagulation or fibrinolysis the circuit was changed. patient management and monitoring on ecmo at initiation of ecmo the patients were normally sedated and often paralyzed as well. muscle relaxation was withdrawn as soon as the patients were on bypass. the degree of sedation was gradually decreased, and by the end of the run the patients were only mildly sedated at night. during the day they were generally awake, able to communicate with the staff and with their family, watching television, etc. paco was adjusted by adding co to the sweep gas to stimulate spontaneous breathing in pressure-supported ventilation. tidal volumes as measured by the siemens ventilator were recorded on an hourly basis. initially most patients were on total parenteral nutrition. this was gradually withdrawn, and enteral feeding was given through a nasogastric tube as soon as possible. great effort was made to diurese the patients to dry weight. if necessary continuous v-v hemofiltration and/or hemodialysis (cvvhdf) was initiated via the ecmo circuit. during bypass the hemoglobin was kept higher than g/l and the platelets higher than , /ml. antibiotics were selected by results from bacterial cultures performed daily from blood and weekly from cannulation sites, urine, and nasopharynx. examinations for fungus and virus were performed when needed. corticosteroids were not used routinely. in two patients with ecmo duration exceeding days it was given before decannulation. chest radiography was performed every ± days, echocardiography weekly for cannula position, and level of pulmonary hypertension and computed tomography of head, thorax, and abdomen when needed. the patients were monitored and nursed continuously h/day by an ecmo specialist familiar with the principles of ecmo and with detailed knowledge of all the technical equipment and management of patients on ecmo. an ecmo physician or another ecmo specialist was in house h/day during the ecmo run for safety and back-up reasons. the technical monitoring of the patient resembles that of a standard icu patient. since it has been possible for the team to transport patients between hospitals while on ecmo. a special mobile ecmo cart for transportation has been developed. the components are principally the same as described above but include a more powerful battery back-up. a team consisting of one ecmo physician, one ecmo specialist, and one cannulating surgeon initiated ecmo at the referring hospital. the patient is brought back to our institution by ground, helicopter, or fixed-wing craft [ , ] . maximal extracorporeal o delivery expressed in ml/min was calculated in each patient according to ecc . ( -s v o ) hb, where ecc is the extracorporeal flow in l/min, s v o is the mixed venous saturation obtained from the venous return from the patient (before the blood enters the membrane oxygenator) and hb is the hemoglobin concentration in grams/liter. data are presented as mean sd unless otherwise stated. between december and october we have treated adults ( men, women) aged ± years (mean ) for ecmo in our institution. patient data are given in table . they had all been referred to us from other hospitals in sweden and norway. twelve patients had previously been healthy. among the others there was a history of mild diabetes, obesity, psychiatric disorder, crohn's disease, or alcohol abuse. ards was caused by pneumonia/septicemia in ten, by trauma and postpartum pulmonary embolism in two each, and by wegner granulomatosis, aspiration, and nortriptylin intoxication in one each. before ecmo the patients had been ventilated for ± days (mean ). inhaled no had been tried in patients, and had also been treated in the prone position. the mean p a o /fio ratio was ( ± ). the murray score [ ] was . ± . (mean . ). many patients were extremely edematous before the start of ecmo. in of the patients we had access to data on the pre-ecmo weight as well as their normal weight. their pre-ecmo overweight averaged (± to ) kg. of the patients cannulated for ecmo, stable bypass was established in . one patient (no. ), who had unstable hemodynamics by the time of cannulation, rapidly deteriorated with arrythmias and ventricular fibrillation after cannulation. adequate venous return was never achieved, and in spite of rapid conversion to v-a bypass the patient could not be saved. autopsy showed massive pulmonary embolism. data from this patient are excluded in statistical calculations except in calculation of survival. of the remaining patients survived to hospital discharge. the average length of bypass was . days (range ± ; table ). there was no significant difference in this respect between survivors (mean . days, range ± ) and nonsurvivors (mean days, range ± ). table pre-cmo patient data, including which patients were treated with inhaled no, hfov, and prone position (pip peak inspiratory pressure, peep positive end-expiratory pressure, hfov high-frequency oscillatory ventilation, pneu/sept pneumonia or septicemia, wg wegner's granulomatosis, over-weight weight at ecmo start ± normal weight, pre-ecmo pip/peep the last values before ecmo; tidal volume the value obtained from the ventilator also including dead space) eight patients were initially cannulated for v-a bypass and nine for v-v bypass. of the last nine patients only three were put on v-a bypass. the mode of bypass was changed in two cases. one patient initially on v-v bypass was recannulated for v-a bypass because of substantial increase in pulmonary vascular resistance leading to right heart failure and hepatic malfunction. another patient treated with v-a bypass for days was electively decannulated after pulmonary improvement, but deteriorated the following hours and was then recannulated for v-v bypass for additional days. the maximal extracorporeal blood flow during the ecmo run was . . l/min and the maximal extracorporeal oxygen delivery was ml/min, with no significant difference between survivors ( ) and nonsurvivors ( ). surgical procedures during the ecmo run were performed in one-half of the patients. four patients needed revision of the cannulation site or adjustment of the position of one or both of the cannulas. six patients had a tracheostomy performed during bypass. in one case a subsequent revision was necessary because of bleeding. thoracotomy was performed in three of the patients because of pleural effusion or hemothorax as a complication of insertion of pleural drainage. in one of them (no. ) the bleeding was controlled after the first procedure. the next (no. ) required another thoracotomy due to rebleeding after days. after meticulous surgical control of the bleeding, the hemithorax was packed with sponges instilled with e-aminocaproic acid [ ] . the sponges were removed h later and the wound closed. the third patient subjected to a thoracotomy during bypass (no. ) had the hemithorax packed with sponges in the same way during the first procedure and subsequently removed. the bleeding was then controlled and further surgery in these patients unnecessary. two patients had hemopericardium (detected on ecmo day in no. and on day in no. ), and drainage was inserted and kept in place until decannulation. in patient no. ultrasonography showed a perforation of the venous cannula through the wall of the right atrium. the cannula was withdrawn approximately position of one or both cannulas adjusted cm. eventually the perforation closed spontaneously, and surgical repair was unnecessary. eight patients required cvvhdf during a part of the ecmo run due to renal failure. in one patient (no. ) the renal dysfunction was a side effect of treatment with aprotinin peri-and postoperatively. in all patients the renal function recovered during bypass and dialysis/hemofiltration could be withdrawn before decannulation. during a total of days of ecmo there were no technical complications. in cases oxygenators or complete circuits were changed due to signs of intravascular (intracircuit) coagulation and/or fibrinolysis. the average duration of one ecmo circuit (oxygenator) was consequently . days. on occasions patients on ecmo were transported within the hospital for computed tomography. the total transfusion of packed red cells was l, fresh frozen plasma l, and platelets l during the ecmo days. the mean average daily transfusion packed red cells per patient was ml, fresh frozen plasma ml, and platelets ml. the mean average daily transfusion of blood products was ml per patient. the lowest tidal volume averaged ml, which increased to a maximum of during the ecmo course. the highest value was higher among survivors ( ml) than among nonsurvivors ( ml). all surviving patients were able to communicate with the staff and their family within ± days after initiation of ecmo. three patients developed severe intracranial complications. all of these patients subsequently died. none of the nonsurvivors ever woke up during the ecmo run. one of them (no. ) had pre-ecmo episodes of hypotension, pronounced hypoxemia, and circulatory arrest. her pulmonary function improved, but she developed cerebral edema and subsequently a total cerebral infarction day after decannulation. one patient developed a cerebral hemorrhage despite stable coagulation parameters and another a cerebral infarction, both on ecmo. both lesions increased in extension, and ecmo had to be withdrawn due to total cerebral infarction. five of the patients were cannulated in the referring hospital and transported on ecmo by ground, helicopter, or fixed-wing craft ( table ). the transports were uneventful and all patients transported on ecmo subsequently survived. successful use of ecmo was first reported in [ ] , and this has been followed by other encouraging reports [ , , ] . a multicenter study of adult ecmo spon-sored by the national institutes of health was completed in , but the results were disappointing as fewer than % of patients in both the ecmo group and the control group survived [ ] . a prospective randomized study [ ] comparing extracorporeal support and advanced conventional treatment showed a slightly lower ( %; but not statistically significant) survival in the treatment group than in the control group ( %). several other reports have shown a higher survival rate in the treatment of ards with extracorporeal support (table ). in the two largest recently published series the survival was of patients [ ] and of patients [ ] . with regard to the murray score [ ] and pao /fio ratio no difference was detected vs. the patients' pre-ecmo condition (table ) . ecmo does not cure the underlying disease of the lungs, but supports the patient and provides gas exchange until the lungs are again capable of this. as a result of this support the lungs can be ventilated at lower inspiratory pressures and with a lower fraction of oxygen and thus further iatrogenic trauma is avoided. treatment of the primary disease and method of patient care such as mode of ventilation on ecmo may differ between centers and may to some extent explain differences in the results. furthermore, the extracorporeal life support can be performed in various ways, which also may explain discrepancies in results. gattinoni et al. [ ] focused principally upon co removal and an almost apnoeic oxygenation, which was also the case in the study by morris et al. [ ] . after initiation of ecmo, however, there is often an increased opacification of the lungs [ ] and decreased compliance, resulting in less oxygenation and a demand for higher inspiratory pressures, which again may become harmful to the lungs. with a higher extracorporeal flow the extracorporeal support may also contribute substantially to the oxygenation of the patient. v-a bypass may provide a nearly total extracorporeal gas exchange if the flow is high enough. with v-v bypass a nearly total oxygenation can also be obtained if the cannulas are positioned so that the recirculation is min- imized, and if a slightly lower arterial saturation is accepted than normally. in the present series of patients survived. ventilatory ªrest settingsº were used after stabilization on bypass and high ventilator pressures were avoided in order not to cause further barotrauma to the lungs throughout the entire ecmo runs. peak inspiratory pressures never exceeded cmh o during ecmo compared to mean value of cmh o before ecmo (table ) . initially on v-v bypass, when the lungs were unable to contribute to any substantial gas exchange, low arterial saturation values were accepted instead. great care was taken to sedate the patients minimally and maintain co values at levels so that patients triggered in pressure-supported ventilation [ ] . although not experimentally confirmed, we have gained the impression that pressure-supported spontaneous breaths are superior to intermittent mandatory positive pressure ventilation. this is based mainly on clinical observations when patients on ecmo are subjected to various surgical procedures and require deep anesthesia including muscle relaxation. as soon as spontaneous breaths ceased, gas exchange over the lungs deteriorates, and the patient requires higher extracorporeal flow. when on spontaneous pressure-supported ventilation, the flows can again be decreased. a randomized multicenter trial [ ] has recently shown beneficial effects of ventilation with lower inspiratory pressures and lower tidal volumes than conventional in the treatment of ards without ecmo. mortality was lower among patients ventilated with an initial tidal volume of ml/kg bodyweight than those ventilated with a tidal volume of ml/kg. inflammatory mediators were more elevated in ards patients ventilated with high inspiratory pressures than in patients ventilated with lower pressures in another randomized study [ ] . these data together with the present results suggest that a lung protective strategy regarding ventilation is important in the treatment of ards. four patients in the present series died. in the first patient a stable bypass could never be established. at autopsy massive thrombotic masses were seen in the right atrium and emboli in the pulmonary artery. although the cannulation may have contributed to pulmonary embolization, the thrombotic masses in the right atrium could hardly be compatible with life for an extended period, an opinion supported by the fact that the circulation was unstable prior to cannulation. the other three patients who succumbed had intracranial complications incompatible with life. they never regained consciousness during ecmo despite withdrawal of sedatives. computed tomography was therefore performed, and this showed the intracranial complication. theoretically, cerebral infarction is the only complication that cannot be treated while on ecmo, and a total cerebral infarction is an obvious indication for withdrawal of extracorporeal therapy. irreversible lung dis-ease has been considered an indication for withdrawal of extracorporeal support [ , ] . for the same reason, a pre-ecmo ventilatory treatment exceeding ± days is considered a contraindication for ecmo in several centers as the ventilator injury may have caused irreversible lung damage. seven of the patients in the present series had been ventilated at least days before initiation of ecmo. two of them subsequently died for the reasons given above. to date, however, we know of no method to determine when the disease is irreversible. lung biopsy shows only the condition of the tissue being examined, and a diagnosis of irreversibility based on this specimen presupposes that the disease is uniform in all parts of both lungs [ ] . the present findings also illustrate that total lack of pulmonary function and pulmonary hypertension does not indicate irreversibility. in of the patients reported the ecmo run time was or exceeded weeks. in all of these patients practically no pulmonary function was demonstrable during the first weeks. in the patient with the longest extracorporeal life support (no. ), the first signs of any significant gas exchange over the lungs were seen after days on bypass. bleeding has been a significant problem during ecmo treatment, with average blood losses up to ml/day [ ] , and uncontrolled bleeding has been considered an indication for withdrawal of therapy [ ]. use of heparinized surfaces (carmeda bioactive surface) is also accomplished with a need of substantial blood product transfusions (mean . u packed red blood cells and . u fresh frozen plasma) [ ] . in another study using nonheparinized equipment the daily need of transfusions averaged . u red blood cells and . u fresh frozen plasma (median . and . , respectively) [ ] . although the exact volume was not given in these reports, the need of transfusion seems to have exceeded ml/day, suggesting that the volume of an average unit exceeded ml. in the present study the mean daily need for blood products (red blood cells, plasma, and platelets) was only ml. this comparatively low bleeding may be explained by the combination of active surgery and the fact that coagulation parameters were monitored daily, and that the circuits were changed when there were signs of intravascular (intracircuit) coagulation and/or fibrinolysis. patient complications demanding surgical intervention were seen in several of the patients. three patients were subjected to thoracotomies due to hemothorax. although one patient required reoperation due to continued bleeding, the hemothorax was eventually controlled in all cases, and the surgical procedures well tolerated by all patients. from our experience therefore, fear of bleeding complications should not prevent the patients from having necessary surgical procedures. in the multicenter study on hospital survival rates in patients with ards reported by vasilyev et al. [ ] there were patients with a pao /fio ratio of less than . only of these patients survived. provided that their patient group was similar to ours, the difference in survival between ªconventionalº treatment according to the different centers' protocols ( . %) and ecmo treatment according to the protocol described in our present report ( / , %) is highly significant (p < . , c test). standardized treatment protocols for ards including ecmo have also shown a high survival [ , ] . a prospective randomized controlled trial similar to that performed in neonates [ ] is necessary definitely to evaluate whether ecmo for ards in adult patients is life saving and will shortly be initiated [ ] . follow-up investigations regarding pulmonary function, physical performance, and quality of life of the surviving patients in the present material will be performed. experience reported from other centers, however, indicates that long-term survivors after ecmo have an almost equal quality of life as survivors from ards without ecmo and as control patients [ ] . ecmo is a highly invasive procedure and should only be used when so-called conventional treatment fails. v-a is more invasive than v-v bypass as it carries the potential risk of infusing arterial emboli. furthermore, v-a bypass involves ligation of the right common carotid artery in order to infuse to oxygenated blood in the aortic root. before ligation we normally clamp the artery and measure the pressure above the clamp to ensure an adequate collateral circulation, either through the circle of willis or via the right external carotid artery. in the present series v-a ecmo was used only in cases of hemodynamic instability or transportation on bypass. in none of the nine patients on v-a bypass were there any neurological complications which could be attributed to the carotid ligation or arterial embolism. the four nonsurvivors in the overall series were all initially on v-v bypass (one was eventually converted to v-a). bleeding complications are among the most common complications in ecmo [ ] but can generally be managed as outlined above. an immediate and aggressive approach is mandatory even if it involves a major surgical procedure. extracranial bleeding should not be regarded as an indication for withdrawal of ecmo. in conclusion, it has been shown that a high survival rate, far exceeding that which is expected with conventional therapy, can be obtained in adult patients with severe ards using ecmo and spontaneous pressuresupported ventilation with minimal sedation. surgical complications are amenable for surgical treatment during ecmo, and bleeding problems can generally be controlled. it is difficult or impossible to decide when a lung disease is irreversible, and prolonged ecmo treatment may be successful even in the absence of any detectable lung function. ecmo ± extracorporeal cardiopulmonary support in critical care. extracorporeal life support organization ecmo ± extracorporeal cardiopulmonary support in critical care. extracorporeal life support organization management of ecls in adult respiratory failure ecmo ± extracorporeal cardiopulmonary support in critical care. extracorporeal life support organization inflight use of extracorporeal membrane oxygenation for severe neonatal respiratory failure inter-hospital transport of neonatal patients on extracorporeal membrane oxygenation: mobile-ecmo an expanded definition of the adult respiratory distress syndrome local treatment with tranexamic acid decreases the risk of hemorrhagic complications after thoracotomy during ecmo treatment. presented at the th annual children's extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome): use of the bramson membrane lung clinical effects of membrane lung support for acute respiratory failure ten years of use of extracorporeal membrane oxygenation (ecmo) in the treatment of acute respiratory insufficiency (ari) membrane oxygenators in prolonged assisted extracorporeal circulation extracorporeal membrane oxygenation: potential for adults and children extracorporeal membrane oxygenation in adults: radiographic findings and correlation of lung opacity with patient mortality successful extracorporeal membrane oxygenation in four children with malignant disease and severe pneumocystis carinii pneumonia ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial open lung biopsy in pediatric patients on extracorporeal membrane oxygenation low-frequency positive-pressure ventilation with extracorporeal co removal in severe acute respiratory failure an approach to the treatment of severe adult respiratory failure uk collaborative randomised trial of neonatal extracorporeal membrane oxygenation. uk collaborative ecmo trial group presentation at the th annual meeting of the extracorporeal life support organization health-related quality of life. long-term survival in patients with ards following extracorporeal membrane oxygenation (ecmo) extracorporeal life support. the university of michigan experience venovenous extracorporeal membrane oxygenation (ecmo) with a heparin-lock bypass system extracorporeal carbon dioxide removal and low-frequency positive-pressure ventilation. improvement in arterial oxygenation with reduction of risk of pulmonary barotrauma in patients with adult respiratory distress syndrome extracorporeal gas exchange in adult respiratory distress syndrome: associated morbidity and its surgical treatment key: cord- -danl io authors: jansen, oliver; kamp, oliver; waydhas, christian; rausch, valentin; schildhauer, thomas armin; strauch, justus; buchwald, dirk; hamsen, uwe title: extracorporeal membrane oxygenation in spina bifida and (h n )-induced acute respiratory distress syndrome date: - - journal: j artif organs doi: . /s - - - sha: doc_id: cord_uid: danl io acute respiratory distress syndrome (ards) is characterized as an acute hypoxemic and/or hypercapnic respiratory failure seen in critically ill patients and is still, although decreased over the past few years, associated with high mortality. furthermore, ards may be a life-threatening complication of h n pneumonia. we report on a -year-old spina bifida patient with confirmed h n influenza virus infection causing acute respiratory failure, who was successfully weaned from -day veno-venous extracorporeal membrane oxygenation (vv-ecmo) treatment with an excellent outcome. due to the physical constitution of spina bifida patients, we experienced challenges concerning cannula positioning and mechanical ventilation settings during weaning. acute respiratory distress syndrome (ards) is a severe respiratory condition characterized by diffuse inflammation of alveolar and vascular (capillary) lung structures leading to progressive hypoxemia and/or hypercapnia. the american-european consensus conference definition has been applied since its publication in and has helped to improve knowledge about ards. however, in , the european intensive medicine society agreed on the berlin definition, which is now widely applied and accepted in diagnosis of ards [ ] . in the management of patients with ards, extracorporeal membrane oxygenation (ecmo) has been successfully used as salvage therapy. ards severe enough to require ecmo therapy is estimated to occur in nearly - cases per million population per year [ ] . the effectiveness of ecmo in ards patients with pneumonia, influenza a (h n ), and/or trauma has recently been described and considered promising [ , ] , although is still associated with higher mortality [ ] . the addition of prone positioning therapy to ecmo may improve alveolar recruitment and, therefore, reduce ventilator-induced lung injury [ , ] . adding prone positioning therapy to ecmo patients is recommended by the guidelines for adult respiratory failure from the extracorporeal life support organization if radiological imaging shows posterior consolidation of the lung fields [ ] . a -year-old (height cm and kg bodyweight) chronic paraplegic patient due to spina bifida presenting an extraordinary kyphoscoliosis (see fig. ) was admitted to the intensive care unit (icu) after onset of an acute respiratory failure due to h n influenza. prior to ards onset, the patient underwent urologic treatment for pyelonephritis that had led to sepsis and required intensive medical care. as respiratory failure proceeded and pulmonary function could not be maintained despite extensive mechanical ventilation (mv), the patient met the criteria for extracorporeal membrane oxygenation (ecmo) and has, therefore, been transferred to our hospital (ecmo center). according to the patients' medical history, a magnetic resonance imaging (mri) conducted years ago showed no signs of chiari malformation. microbial testing revealed h n virus infection as the probable cause for the ongoing ards. his chest x-ray and computed tomography (ct) showed diffuse bilateral infiltration, and blood gas test showed a severe hypoxemia and hypercapnia refractory to the conventional mv (table ; fig. ). on the day of admission and after completion of diagnosis, we percutaneously (right jugular vein french size + right femoral vein french size) administered a veno-venous extracorporeal membrane oxygenation. cannula (maquet hls, rastatt, germany) positioning has been verified immediately using ultrasound, but was challenging due to a monstrous thoracic scoliosis. the cannulation is always performed in cooperation with the cardiotechnology following a standardized protocol. subsequently, mv settings were adjusted to ensure protective ventilation. because of the patients distinct physical constitution, the pump flow strongly depended on the positioning of the patient. very small positional changes (head tilt and rotation, hip flexion, or rotation) caused severe, recurrent, and prolonged episodes of decreased blood flow rate and increased negative pressure of the venous inflow, leading to an inadequate systemic oxygenation and to an increased risk of intraoxygenator blood clotting. therefore, patient and cannula positioning had to be adapted constantly. once the negative pressure exceeded a limit value and subsequently ecmo blood flow decreased, we immediately tried to ensure optimal suction of the ecmo cannula by small changes in the position of the body. in the event of persistent insufficient blood flow, we performed whole body position changes (e.g., head-low, legs-up, / / °). due to the enormous physical deformation, especially, whole body changes proved to be challenging and required partly improvised support aids. due to that there is no standardized protocol/regimen available, concerning ecmo therapy and positioning therapy in patients suffering challenging deformity, we adapted to incident by trial and error but agreed on the following scheme to solve the recurrent inflow pressure problems: st step checking for kinking of the cannules; nd step minimal body changes, e.g., head tilt and rotation, hip flexion, or rotation; rd step whole body position changes, e.g., head-low, legs-up, / / °. in the initial stage, moving the patients' body/body positioning therapy was conducted only to maintain or improve ecmo blood flow (see scheme above). on the th day of ecmo therapy as episodes of decreased blood flow rates persisted and one oxygenator already had to be replaced, the blood flow direction was reversed. although the pump flow remained strongly dependent on the patients position, the incidence and duration of decreased blood flow periods decreased. however, until termination of ecmo therapy and due to clotting, a total of three oxygenators had to be replaced as the patient highly depended on the extracorporeal oxygenation. meanwhile, the patients underwent percutaneous dilatational tracheostomy and as septic multi organ failure proceeded received continuous renal replacement. as ecmo blood flow could be reduced and, therefore, resulted in less inflow pressure problems and less dependency on the patients' position, we began to establish a regimen of intermittent prone positioning therapy to improve alveolar recruitment of the posterior consolidated lung fields and, therefore, pulmonary capacity (fig. ) . as the respiratory function improved, ecmo support was gradually decreased and terminated after days. prior to ecmo termination, blood flow has been lowered to two l/ min and oxygen flow down to l/min (withdrawal trial). days after ecmo removal, we transferred the patient at his own wish closer to his home to a clinic specialized on prolonged weaning from mv. at the time of discharge from our hospital, he was able to breath spontaneously for short periods of time depending after additional weeks, the patient was discharged to a rehabilitation center, breathing spontaneously and being able to mobilize himself in his wheelchair. severe kyphoscoliosis causing restrictive respiratory impairment may result or predispose acute respiratory failure [ ] . in addition, spinal cord injury (sci), due to several factors, e.g., reduction in respiratory muscle strength, fatigue (motor impairment), retention of secretions (ineffective coughing) [ ] aggravate the risk of respiratory failure. although pulmonary complications in sci patients are common, yet, there is insufficient evidence about their management; current practice is mainly based on clinical experience and expert opinion [ ] . ecmo is increasingly emerging into the icus and ards therapy. depending on the physical constitution of the patient, ecmo therapy and/or cannula positioning may be more challenging in patients suffering physical deformities. technical complications of ecmo therapy responsible for acute pump or circuit dysfunction are fortunately not common, but if so may cause devastating ecmo therapy failure [ ] . literature review on ecmo in sci, spina bifida, or severe kyphoscoliosis reveals a lack of evidence. to our knowledge, only one case series (n = ) of ecmo in sci addresses this specific issue [ ] . the intention was to provide the experiences of long-term ecmo therapy in a spina bifida patient. although the patient of this present case suffered severe technical complications due to spina bifida deformity, ecmo is feasible and the outcome was excellent. while experiencing recurrent episodes of increased negative pressure of the venous inflow and decreased blood flow rates in the initial stage, we applied positioning therapy (e.g., / and ° positioning) to resolve the inflow complications. alternatively, the addition of a second venous inflow cannula may significantly increase blood flow rate and decrease negative pressure (suction) of the venous inflow line [ ] . however, at the end of the ecmo treatment and once the patients' pulmonary function had been improved/partially restored and the patient showed less dependency on ecmo, we were able established a positioning therapy regimen including the prone position as an adjunct to ecmo without experiencing any technical problems. similarly, a systematic review by culbreth et al. also reported limited complications and highlighted the clinical efficacy, although evidence is still insufficient [ ] . however, both prone positioning and ecmo are well established in treating refractory hypoxemia in ards. combining these therapies may increase the potential risk of cannula dislodgement. this case report suggests that these therapy options can be used in tandem despite considerable physical deformities. acute respiratory distress syndrome: the berlin definition international ecmo network (ecmonet). position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome cesar trial collaboration. efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomized controlled trial mortality trends of acute respiratory distress syndrome in the united states from to prone positioning in severe acute respiratory distress syndrome prone position during ecmo is safe and improves oxygenation nocturnal mechanical ventilation improves exercise capacity in kyphoscoliostic patients with respiratory impairment extracor poreal life suppor t organization. guidelines for adult respiratory failure. . https:// w w w respiratory management during the first five days after spinal cord injury respiratory management following spinal cord injury: a clinical practice guideline for health-care professionals technical complications during veno-venous extracorporeal membrane oxygenation and their relevance predicting a system-exchangeretrospective analysis of cases extracorporeal lung support in patients with spinal cord injury: single center experience double-stage venous cannulation combined with avalon® cannula for potential prolongation of respiratory ecmo in end-stage pulmonary disease complications of prone positioning during extracorporeal membrane oxygenation for respiratory failure: a systematic review key: cord- - b zaur authors: buchtele, nina; staudinger, thomas; schwameis, michael; schörgenhofer, christian; herkner, harald; hermann, alexander title: feasibility and safety of watershed detection by contrast-enhanced ultrasound in patients receiving peripheral venoarterial extracorporeal membrane oxygenation: a prospective observational study date: - - journal: crit care doi: . /s - - -y sha: doc_id: cord_uid: b zaur nan in bifemoral venoarterial extracorporeal membrane oxygenation (va ecmo), the transition point at which the antegrade pulsatile output from the left ventricle and the retrograde non-pulsatile ecmo output collide is referred to as watershed [ ] . currently, no standard method is available to determine its location. occasionally, contrast-enhanced computed tomography (ct) or angiography has been used [ ] [ ] [ ] . both techniques, however, bear disadvantages including radiation exposure and use of iodinated contrast media. we assessed the feasibility and safety of contrast-enhanced ultrasound (ceus) to detect the watershed at the bedside in patients on bifemoral va ecmo at three icus of a european tertiary care facility. ceus was performed as soon as possible after ecmoinitiation (cardiohelp, maquet, germany) using sono-vue contrast media (bracco, italy). transesophageal echocardiography (x - t probe) and transabdominal sonography ( - mhz curvilinear probe) were performed concomitantly to display mid-esophageal aortic valve, ascending, descending aorta, and upper esophageal aortic arch long-axis views as well as longitudinal views of the proximal (below diaphragm), mid (level of renal arteries), and distal (above iliac bifurcation) abdominal aorta. the mechanical index was set to . - . field of view. prior to ceus, the arterial bubble sensor activating zero-flow mode was disabled. the acoustic alarm was kept active. the presence or absence of pulsatility in the left radial artery was documented. one milliliter of sonovue was administered via the venous drainage cannula, followed by a flush of ml normal saline. the obtained images were evaluated qualitatively. if a watershed area was not able to be visualized, contrast-enhanced blood flow was classified into "pulsatile" or "continuous" to discriminate between cardiac and ecmo blood flow. the feasibility of ceus was assessed based on qualitative image evaluation, the amount of contrast media administered, and the rate of bubble detection. secondary outcomes were safety and frequency of radial arterial pulsatility. safety variables included ecmo settings, hemodynamics, and neurologic assessment and were obtained over a -h period after ceus. the variables are presented as absolute values (n), relative frequencies (%), and median ( - % iqr). we used random-effects general linear regression models to estimate mean changes for each safety variable (mean ± sd). between august and april , ten patients were enrolled (table ) . qualitative detection of watershed location by ceus was feasible using ml contrast media. in five patients, the watershed could be clearly shown in the abdominal aorta, seconds after contrast media administration (fig. ). in the remaining five patients, contrast-enhanced continuous blood flow was visible throughout the abdominal and thoracic aorta indicating watershed location close to the aortic root. the pulsatility of the left radial arterial waveform and opening of the aortic valve was present in all patients. acoustic bubble detection occurred in all patients after ceus. no changes in the safety variables related to ceus occurred (table ) . ct imaging of the brain ( / patients) showed no cerebral lesions suggesting particle embolism. this study assessed the feasibility of ceus for watershed detection at the bedside in patients on bifemoral va ecmo. ceus was apparently safe and provided realtime assessment of the watershed or contrast-enhanced continuous blood flow in the aorta. increasing evidence indicates that ceus is safe in critically ill patients, and application areas are ever-expanding [ ] [ ] [ ] . in bifemoral va ecmo, ceus may help to identify patients at risk for differential hypoxia, given that left radial arterial pulsatility was present in all study patients, including those in whom the watershed was located near the aortic root. transthoracic suprasternal echocardiography may be useful to localize the watershed in the aortic arch but has not been tested. furthermore, no reference imaging technique has been used to assess the performance of ceus, because no standard method for the detection of the watershed is available, and no repeated measurements were performed. abbreviations ceus: contrast-enhanced ultrasound; ct: computed tomography; va ecmo: venoarterial extracorporeal membrane oxygenation fig. visualization of contrast-enhanced retrograde non-pulsatile ecmo blood flow. the watershed is marked with an arrow and located distal to the superior mesenteric artery extracorporeal membrane oxygenation watershed heart against venoarterial ecmo: competition visualized hemodynamic changes in patients with extracorporeal membrane oxygenation (ecmo) demonstrated by contrast-enhanced ct examinations -implications for image acquisition technique safety and feasibility of contrast echocardiography for ecmo evaluation safety and feasibility of contrast echocardiography for lvad evaluation acute kidney injury is associated with a decrease in cortical renal perfusion during septic shock publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we gratefully thank our collaborators gerhard ruzicka, christoph weiser, hans domanovits, alexander o. spiel, peter schellongowski, andja bojic, anne merrelaar, and monika schmid for their valuable help with patient recruitment, performing ultrasound and study flow throughout the study. we thank sarah ely for the thorough revision of the manuscript. authors' contributions nb, ms, and ts designed the study. nb, ms, cs, and ah enrolled the study patients and/or performed the ultrasound. nb, ms, and cs collected the data together with the trained study nurses. nb, ms, and ts analyzed and interpreted the data. hh did the statistical analysis. nb and ms wrote the first draft of the manuscript and drew the figure and table. all authors critically revised the manuscript for important intellectual content and approved its current version. all authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. the manuscript has not been previously published and is not under consideration for publication in the same or substantially similar form in any other peerreviewed media. this study was supported by the austrian society for internal medicine and general intensive care and emergency medicine (Ögiain). the datasets analyzed during the current study are available from the corresponding author on reasonable request. complete results from safety data are available with the main manuscript. exemplary ultrasound loops are available from the corresponding author on request. the study was approved by the ethics committee of the medical university of vienna (ec# / ) and conducted in accordance with helsinki declarations. according to austrian law regulations, prior to the study enrolment, a waiver was obtained and patients were informed about their participation after regaining consciousness. the authors declare that they have no competing interests. key: cord- - gpwf z authors: nan title: abstracts from the first international conference on heart failure in children and young adults date: journal: pediatr cardiol doi: . /s - - - sha: doc_id: cord_uid: gpwf z nan safety of endomyocardial biopsy in children < years of age with dilated cardiomyopathy or myocarditis. debra a. dodd, md and thomas p. doyle, md., vanderbilt children's hospital, nashville, tn. concerns have been raised by others regarding the safety of biopsy in infants and young children with dilated cardiomyopathy (dcm) or myocarditis, with risk of perforation being reported as high as % in this group. at the same time, the utilization of heart transplantation for dcm, the availability of immunosuppression and prolonged extracorporeal membrane oxygenation (ecmo) for the management of myocarditis, and the lack of reliable noninvasive methods to separate these two diagnoses, make biopsy more imperative. since we have planned to biopsy all infants outside the immediate newborn period ( > days) presenting with ventricular dilatation and low ejection fraction. charts were reviewed retrospectively. infants underwent cardiac biopsy from the femoral approach while sedated at a median age of months (range weeks- . years), and median weight of . kg (range . - . kg). biopsies were done at a median days (range - days) after the diagnosis. this included patients with delayed referral from elsewhere. / were on inotropic support at the time of the biopsy. / underwent a nondiagnostic skeletal muscle biopsy prior to endomyocardial biopsy. two other infants met the above criteria for biopsy but were felt to be too unstable, with both being placed on ecmo within hours of presentation. four infants presented in the first month of life at a median age of days (range - days) and a median weight of . kg (range . - . kg) and did not undergo biopsy. in the patients who underwent biopsy, the only complication was an episode of svt converted with adenosine. there were no cardiac perforations. a median of pieces (range - ) was obtained from the right ventricle in each patient. lymphocytic infiltrate was seen in two patients, mito- abstracts-heart failure in children and adults chondrial abnormalities diagnostic of barth's syndrome in one patient, vacuole laden macrophages diagnostic of a storage disease in one patient, no abnormalities on routine stains but significant myofilament loss on electron microscopy in two patients, and nonspecific findings of hypertrophy and/or fibrosis in the remaining patients. our results suggest that endomyocardial biopsy can be done safely in most infants with dcm or myocarditis, and we feel it does contribute to optimal management of these patients. purpose: endomyocardial biopsy (emb) is routinely carried out in adults prior to cardiac transplantation but remains controversial in children. this study aims to determine the incidence of myocarditis in paediatric patients transplanted following a clinical diagnosis of dilated cardiomyopathy (dcm). methods: archived slides were examined from the explanted hearts of all paediatric patients transplanted for a diagnosis of dcm at the freeman hospital since the transplant programme began, between and . control slides were examined from the explanted hearts of patients transplanted for a diagnosis of congenital heart disease. slides were examined by two specialist histopathologists using a light microscope, in a blinded manner, and scored according to the dallas criteria. results: hearts were examined ( with dcm and controls). the control patients showed no evidence of myocarditis. on examination active myocarditis was found in two patients ( %). some evidence of inflammation was found in a further patients ( %). we divided these into ''borderline'' myocarditis ( %) and minimal inflammation ( %). this might suggest previous myocarditis. the results of this study indicate a high prevalence of inflammation in the explanted hearts of children who have undergone transplantation for a diagnosis of dcm. only % had acute myocarditis. there is a need for an improved classification of the common intermediate changes that may help elucidate the cause of heart failure in this group. this has important implications on many aspects of management of sick children with heart failure with presumed dcm. when discussing the issue of biopsy for these seriously ill children the meaning of the intermediate forms of inflammation needs to be better understood. purpose: to investigate whether n terminal pro-brain natriuretic peptide (ntpro-bnp) is elevated in children with dilated cardiomyopathy (dcm), and therefore to assess whether ntpro-bnp is applicable as a marker of heart failure in children as it is in adults. methods: eight children under years with cardiac failure (fs results: plasma ntpro-bnp levels were significantly elevated in children with dcm (mean pg/ml, range: pg/ml to pg/ml) compared to control children (mean pg/ml, range: pg/ml to pg/ml), p = . . the number of patients recruited was not sufficient to determine any correlation of ntpro-bnp with disease severity. conclusion: the findings of this study suggest that plasma levels of ntpro-bnp are elevated in children with dcm and its use as a marker of heart failure in adults may also be applicable to children. this was previously unreported in the paediatric population. the wide separation of ntpro-bnp levels between the normal children and those with clinical heart failure, with no healthy control child having an ntpro-bnp level > pg/ml and no heart failure patient having an ntpro-bnp level < pg/ml, suggests that this may be a useful clinical tool in the diagnosis of less severe forms of heart failure and a means of monitoring progress in children. abbreviations: dilated cardiomyopathy (dcm), n terminal pro-brain natriuretic peptide (ntpro-bnp), fractional shortening (fs) key words: heart failure, pediatrics, dilated cardiomyopathy, and brain natriuretic peptide background: nesiritide (r-bnp) has been shown to rapidly improve hemodynamics and induce diuresis in adults with moderate to severe congestive heart failure (chf). however, description of its use in pediatric patients is scarce. purpose: review and analysis of our experience with r-bnp in pediatric patients with chf. methods: review of instances of use in patients based on their response in urine output (uop), weight change, dyspnea (nyha classification), and renal indices (bun/cr). results: the etiologies of heart failure were varied: (a) systolic dysfunction in a year-old male with dilated cardiomyopathy secondary to duchenne muscular dystrophy, (b) ''failed fontan'' in a year-old female with complex congenital heart disease, and (c) severe diastolic dysfunction in a year-old male heart transplant recipient ( administrations). each received r-bnp ( mcg/kg bolus followed by . mcg/kg/min infusion) for hours while continuing intravenous bolus diuretics. patient c also received continuous infusions of torsemide, milrinone, and ''renal-dose'' dopamine prior to and during r-bnp. three administrations were in the icu with frequent, non-invasive vital sign monitoring, with the other (c ) receiving continuous central venous and intra-arterial pressure monitoring. in cases (a, c , and c ), improved uop, bun/cr, weight loss, and decreased dyspnea were seen. in cases (a and c ) the changes were sustained. subject a had no change until hours after discontinuation of r-bnp at which point uop increased from . to > . cc/kr/hr and was sustained over the ensuing hours. his nyha class decreased from iii to ii. subject c's uop increased from . to > . cc/kg/hr within hours of initiating r-bnp. improvement in bun/cr and nyha scale (iii to ii) was sustained for days after discontinuation of r-bnp despite weaning of additional therapies. chf symptoms relapsed and days later, he received a second infusion (for hours). all parameters improved in the initial hours followed by a blunted response with a decline in uop, increased dyspnea, weight gain, and worsened bun/cr despite addition of dopamine. subject b (nyha ii) had no response to any of the parameters. subject a developed asymptomatic hypotension that resolved within hours of holding r-bnp. otherwise, vital signs were stable in all subjects and improved, in general, in those who responded favorably to r-bnp. no arrhythmia or increased ectopy was seen in any of the subjects. baseline hyponatremia in subjects a and c worsened from to and to meq/l, respectively, but later recovered. patients a and b survived to discharge and patient c survived to re-transplant. conclusions: nesiritide can be used safely in pediatric subjects with moderately severe decompensated heart failure. the clinical response varies from rapid and sustained to delayed and blunted. the lack of response in the subject with fontan physiology may be secondary to a different mechanism of chf. key words: nesiritide, b-type natriuretic peptide, pediatric congestive heart failure outcome of fulminant viral myocarditis in the pediatric population. n amabile, a fraisse, p chetaille, f aubert, j camboulives, jf pellissier, p djiane., hopital de la timone, marseille, france. background: in the adult population, fulminant myocarditis is characterized by critical illness at presentation but excellent long-term survival. we sought to highlight clinical features and outcome in the pediatric population. methods: we report the evolution of children admitted for fulminant myocarditis to our institution since . inclusion criteria were the presence of an acute and severe heart failure associated with a history consistent with the presence of a viral illness within the weeks before admission, without personal or familial antecedent of cardiomyopathy. results: the median age at presentation was year ( - years). initial left ventricular ejection fraction by echocardiography ranged from to % (mean: %). endomyocardial biopsy was performed in patients and revealed histological signs of active myocarditis. a viral agent was identified in cases on serological studies: human parvovirus b (n = ), epstein barr virus (n = ), varicella zoster virus (n = ) and coxsackie (n = ). all children were admitted in intensive care unit. nine patients required intravenous inotropic support and children were intubated. all patients received corticosteroid therapy. in cases, intravenous immunoglobulin infusions ( g/kg) were associated. five subjects experienced cardio-pulmonary arrest during their hospital course with one death. four children had sustained ventricular arrhythmia. median hospitalization time in intensive care unit was days (ranging from to days). subsequent evolution was favourable in the surviving patients. after . years ( . to . ) of median follow-up time, no child has any residual cardiovascular symptom or requires any cardiac medication. no neurologic impairment was observed. left ventricular ejection fraction by echocardiography is normal in all cases (mean: %). conclusions: this study illustrates initial gravity of fulminant myocarditis in pediatric patients and subsequent favourable evolution. aggressive hemodynamic support is warranted for patients with this condition. background: mechanical circulatory support in the postoperative period after pediatric cardiac surgery may be associated with a higher hospital mortality, especially in centers with a low rate of usage. we retrospectively studied all the postoperative patients who required mechanical support in emergency in our institution. since january , children underwent mechanical circulatory support at a median age of ( to ) months, after a median intensive care unit course of ( to ) hours. the surgical procedure was congenital heart disease repair in cases and a cardiac transplantation in one child. five patients were supported with a centrifugal pump whereas a roller pump was used in one case. five patients required support though a veno-arterial cannulation for poor cardiac output with a cardiac arrest in cases. one patient had a veno-venous cannulation for an acute respiratory distress syndrome on the th postoperative day after repair of a tetralogy of fallot. after a median duration of ( to ) days, patients were successfully weaned from support. one patient could not be weaned and died from multiple organ failure. three patients had renal failure, treated successfully with hemofiltration (n = ) or peritoneal dialysis (n = ). no patient had neurological complications. all the survivors were discharged from the hospital. conclusion: emergency post-cardiotomy mechanical support can offer a favorable outcome to selected patients even in centers with a low rate of usage of this procedure. despite prolonged periods of support, our patients did not experienced irreversible neurological events, hemorrhages or infections. there were five children ( patients with chd and patient with ards) who were unable to wean off of ino and mv (avg. days). after initiation of oral sildenafil, all children were weaned off ino (avg. days) and all were successfully weaned from mv (avg. days). two children with severe bpd, requiring chronic ventilation (data not included in table ) were placed on sildenafil. both children were on high mv settings since birth and had failed all other medical management for their phtn. within four months after initiation of sildenafil, one child was discharged to home on low mv settings and the other child had complete reversal of his phtn by echo. no adverse effects of sildenafil, including systemic hypotension, adverse drug interaction, dysrhythmias, anaphylaxis, or headaches occurred in any patients. treatment range was day to several months (some children remain on sildenafil). conclusions: sildenafil appeared to be safe and efficacious at the doses used in this pediatric population. after the initiation of sildenafil, of patients were weaned from ino and of patients were weaned off mv regardless of the etiology of the phtn. prospective trials evaluating the use of sildenafil in pediatric phtn are needed looking at dosing, safety, efficacy, and decreased need for ino. key words: sildenafil, pulmonary hypertension, children. the natriuretic peptide type b (bnp) which is produced in the ventricles of the heart, has been shown to be increased in plasma (p) during different types of hemodynamic overload of the heart. the clinical use of this peptide as a marker of cardiac strain and ventricular dysfunction, however, has not yet been fully established in children with congenital heart defects. aim: to study p-bnp levels in children with congenital heart disease with pressure or volume overload of different morphological ventricles. methods: consecutive blood samples for analysis of p-bnp and p-anp were taken during regular pre-operative investigations (surgery/catheter) in children with congenital heart defects. the hemodynamic load of the heart was evaluated by echo-doppler investigation (echo) and/or during catheterisation. hemodynamic overload of the heart was classified as: pressure overload of the left (pres lv) (aortic stenosis, coarctation of the aorta) or right (pres rv) (pulmonary stenosis) ventricle, volume overload of the left (vol lv) (ventricular septal defect, patent ductus arteriosus) or right (vol rv) (atrial septal defect) ventricle, sufficient to indicate surgery/catheter intervention according to local practice. patient with depressed ventricular function was excluded. twenty-three children without heart disease aged two weeks to . years served as a control group for the natriuretic peptide measurements. the reference intervals for bnp were - . ng/l and for anp - ng/l. results: blood samples were obtained from patients ( boys, girls), mean age , years ( months- . years). the p-bnp was significantly higher in the vol lv group, median . ng/l ( . - ) (n = ), as compared with the vol rv group . ( - . ) (n = ), pres rv group . ( . - . ) (n = ), pres lv group . ( . - ) (n = ) and control group . ( - . ), respectively (p< . ; kruskal wallis). the p-bnp levels were significantly higher compared with the control group for all the groups except for the pres lv group (p< . ). p-bnp correlated with the left ventricle inner diameter in diastole (p = . ) and the ratio of the left atrium/aortic root dimension (p = . ) (spearman rank correlation). the fractional shortening of the left ventricle (fs) was within the normal range in all the groups mean % ( - ). no significant correlation was observed between p-bnp and the fs (p = . ). conclusion: the p-bnp levels increase in children with congenital heart defects during increased hemodynamic load of the heart even in the absence of systolic dysfunction. this increase is particularly pronounced in defects resulting in volume overload and dilation of the left ventricle. key words: bnp, congenital heart defect, volume overload purpose: mechanical support may be required in pediatric patients undergoing open-heart surgery. the target of this short-term support is to maintain adequate end-organ perfusion and to allow the heart to recover. we report our experience with iabp to support pediatric cardiac patients. methods: from / to / , children required iabp support in our institution. eight were infants less than months of age, and the rest were over months. infants' mean age at operation was . ± . ( % ci: . - . ) weeks, and median body weight (bw) was . (range: . - ) kg. children's mean age at operation was . ± . ( % ci: . - . ) years, and median bw was (range: - ) kg. the duration of iabp support was . ± . h in infants, and . ± . h in children. iabp was established: i. due to failure to wean of cardiopulmonary bypass-cpb (n = , infants, children); ii. prophylactically, before weaning of cpb (n = , all infants); iii. postoperatively in the icu, due to hemodynamic deterioration (n = , infant, children). iabp was inserted through the ascending aorta in infants, and through the femoral artery in children. results: there were four early deaths (mortality %). six infants ( %) and nine children ( %) weaned of iabp successfully. two patients required re-exploration for bleeding unrelated to iabp, and for drainage of recurrent loculated pneumothoraces. two infants developed thrombocytopenia. there were two late deaths, one due to mesenteric ischaemia and the other due to svc thrombosis. at a mean follow-up of (range: - ) months all long-term survivors ( . %) showed normal ventricular function. conclusion: iabp is an effective modality of cardiac support in pediatric patients undergoing cardiac surgery. it can be safely used in children as well as in infants. in the latter, iabp insertion through the ascending aorta eliminates possible complications. - introduction: anomalous origin of the left coronary artery from the pulmonary artery (alcapa) is a rare congenital lesion that results in myocardial ischemia. patients with alcapa usually present in infancy but may not be compromised until the second or third decade. impaired cardiac function combined with progressive mitral regurgitation leads to severe congestive cardiac failure or cardiogenic shock. early surgical repair to establish a two coronary system is indicated either by direct coronary reimplantation or intrapulmonary baffling together with mitral valve repair if necessary. long-term results are excellent. methods: between august to september , ten patients with alcapa underwent surgical repair. age was between months and year. m/f was / . eight patients were under months; one years and another years. five infants presented with cardiogenic shock on inotropic support and intubated prior to the surgery. all the patients were associated with moderate to severe mitral regurgitation. the entire group exhibited reduced left ventricular function with minimal ejection fraction of % ( %- %). four patients underwent direct coronary artery reimplantation. five patients were corrected by intrapulmonary baffling whilst the -year-old boy associated with pda and coarctation required a short gortex conduit. results: one infant who presented with cardiogenic shock and gross metabolic acidosis died from multiorgan failure. all survivors showed significant improvement of left ventricular function. one patient who had intrapulmonary baffling repair initially subsequently found baffle leak and pulmonary stenosis due to large baffle underwent reoperation for baffle repair and pulmonary artery augmentation. follow up of all the survivors showed satisfactory left ventricular function (ef %- %) and grade - / mitral valve regurgitation. discussion: alcapa often presents with cardiogenic shock during infancy. surgical repair to establish two coronary systems is the goal of treatment. the results of operation with direct coronary reimplantation or intrapulmonary baffling are excellent. recover of left ventricular function and satisfactory mitral valve function is usual in long-term. intrapulmonary artery baffling may result in supravalvar pulmonary stenosis and baffle leak, which needs close follow up and may require further operation. the left ventricle (lv) has a greater ability to tolerate hemodynamic load than the right ventricle (rv). regulation of this differential response is not known. methods: hypertrophied myocardium was obtained at surgery from acyanotic pediatric pts, lv hypertrophy (lvh) and rv hypertrophy (rvh), age range . - . yrs. diagnoses included subaortic stenosis, subpulmonary stenosis, and hypertrophic cardiomyopathy. gene expression (ge) with affymetrix dna microarray gene chips was performed. after log transformation, differences in mean ge between lvh and rvh groups with p value < . was considered significant. genes with ‡ -fold difference between the groups were characterized and correlated with severity of obstruction. immunohistochemical staining was performed to detect myocyte apoptosis with tunel assay, and fibrosis with trichrome stain in myocardium from pts with lvh and/or rvh. results: there were genes with significant differences in expression between lvh and rvh myocardial samples. genes associated with myocardial hypertrophy, cytoskeleton, apoptosis, and ion channels were up regulated in lvh. rvh group had genes relatively over expressed: extracellular matrix components, phospholipase a and c, and mitochondrial transporter proteins. fetal gene activation was present in both lvh and rvh, with relative over expression of canf and dystrophin in the lv compared to rv (p values <. ). severity of obstructive gradients in both groups correlated positively with actin and myosin ge, and negatively with apoptosis related genes (r = . - . ). anp ge correlated with lv obstruction only. fibrosis and myocyte apoptosis was present in both lvh and rvh specimens, but was greater in pts with hcm than those with isolated outflow tract lesions. conclusion: myocardium from hypertrophied lv and rv has different genomic profiles. upregulation of genes in the lvh group that activate adaptive pathways may contribute to the functional advantage observed in the lv vs. the rv with hemodynamic load, especially in pts with congenital heart disease. further analysis of these candidate genes and downstream signaling effects are warranted. key words: gene expression, ventricular hypertrophy, and congenital heart disease background: extracorporeal membrane oxygenation (ecmo) can be used to support children with severe graft failure after heart transplant (tx). severe graft failure may result from poor myocardial preservation, high pulmonary vascular resistance (pvri) or acute hemodynamic rejection. the use of ecmo as therapy for acute hemodynamic rejection has not been well described. methods: medical records of all patients (pts) requiring ecmo post-tx were reviewed. results: from to , / ( %) pts required ecmo post-tx; age range . wks to yrs. pre-tx diagnoses included: cardiomyopathy ( pts), congenital heart disease ( pts) and lv tumor ( pt). initiation of ecmo occurred - days post-tx. ecmo was necessary to wean from cardiopulmonary bypass in pts; with high pvri, with poor myocardial preservation, and with severe branch pulmonary stenosis. ecmo was initiated in pts< days post-tx for an anaphylactic reaction ( pt) and aspiration pneumonia with high pvri ( pt). two pts with acute hemodynamic rejection required ecmo at month (mo) and . mos post-tx. median ecmo duration was days (range - ). one pt with high pvri died on ecmo day from hemorrhage. eight pts were successfully decannulated and survived to hospital discharge, with a mean follow-up of . ± . yrs (range . - ). one pt with poor myocardial preservation was supported for days as a bridge to retransplant, and pts died from sepsis at mo. and yrs post-tx. ecmo morbidities included: stroke ( pts, with complete resolution of deficits in ), pulmonary hemorrhage ( pts), and cardiac tamponade ( pts). in the pts with graft failure from acute rejection, ecmo duration was and days; both regained normal heart function and were successfully decannulated without complications. conclusions: ecmo is an effective therapy in the child with severe graft failure post-tx, with / pts ( %) surviving to discharge. the indications for ecmo post-tx include treatment of immediate graft failure as well as rescue therapy in the patient with severe acute hemodynamic rejection. key words: ecmo, heart transplant, graft failure, acute hemodynamic rejection background: ventricular assist device (vad) support is well established in treating adults with end-stage heart disease. there are limited data on using vad support in children with acquired or congenital heart disease (chd), or adults with chd. this study describes a single center's experience using vads in this patient (pt) population. methods: retrospective review of pts with chd or cardiomyopathy (cm) who required vad support. results: seven pts were identified. there were pediatric pts, with a mean age of . years ( - )) and mean weight of . kg ( - ); and adult pts ( and years) with a mean weight of . kg. diagnoses in pediatric pts were dilated cm in four, and corrected transposition of the great arteries (ctga) in one pt. one adult pt had ebstein's anomaly of the tricuspid valve and the other had single ventricle and failed fontan. pts were supported for a median duration of days (range to ). devices used were vented-electric heartmate (n = ), thoratec (n = ) and novacor (n = ). routine cannulation was performed for lvad (n = ) or rvad ( pt with ebstein's). the pt with ctga required modified orientation of the device (''back-to-front''). the failed fontan pt had systemic venous and main pulmonary arterial cannulation. outcomes: four pts survived to hospital discharge ( bridged to recovery, bridged to transplant), and died on vad. two deaths were due to neurological complications and one due to fungal sepsis. there was one late death seven months post-transplant due to rejection. at a median follow up of months after vad explantation, the survivors are in nyha class i (n = ) and ii (n = ). conclusions: vads may be used to provide support for pediatric pts with chd or cm, or adults with chd. pathophysiology, anatomy, and size constraints in younger pts impact device implantation, orientation, and management. shortterm survival ( / , %) is similar to that of adult pts with acquired heart disease. key words: mechanical circulatory support, pediatric, vad, congenital heart disease, and cardiomyopathy background: measurement of whole blood b-type natriuretic peptide (bnp) levels has been shown to detect heart failure in adults presenting with dyspnea in the acute setting. because heart failure has varied etiologies and can be difficult to differentiate, and bnp levels are age-dependent, the utility of this test was assessed in children. methods: bnp levels obtained over an -month period were reviewed. indications were known active heart disease compared to unknown etiology of dyspnea or hemodynamic abnormality. the triage Ò bnp bedside elisa test was used. results: of subjects tested (range . - yrs of age), were above yrs and all had childhood forms of heart disease. controls (n = , median age yrs) were later proven to not have active heart disease and bnp was ordered to query presence of cardiac disease/dysfunction. heart disease group (hd, n = , median age yrs) include with restrictive and ( also with single ventricle physiology) with dilated cardiomyopathy (dcar), with shunt or outflow obstruction, and have a fontan. all had normal systolic function except for the dcar group. / controls and / hd were inpatients; and required inotropes/decongestion medications, respectively. excluding the fontan group, the median bnp level was for controls and pgm/ml for hd. using a bnp cutoff of , the sensitivity for active hd in this population was % and specificity %. the positive predictive value was % and negative predictive value %. subjects with a fontan (median age yrs) were separately assessed because they had normal ventricular function and bnp is thought to derive mainly from the ventricles. their bnp's ranged from - , mean , even though were hospitalized and on decongestive drugs for ''failed fontan heart failure''. a total of subjects had concurrent hemodynamic studies. using an rvedp < and pulmonary artery wedge pressure< mmhg as normal filling pressures, the group with normal rvedp and wedge (n = , mean bnp pgm/ml) had a specificity of % and npv % (vs. one high pressure group) and % npv (vs. two high pressures group). the group with high rvedp and wedge (n = , mean bnp pgm/ml) sensitivity was % and ppv %. the group with high rvedp or wedge had a sensitivity of % and ppv %. analyzed by severity of presentation, low severity having< of the following criteria hospitalized, on medication, or dyspnea with routine activity, controls with low severity had a mean bnp vs. hd low severity (ns); high severity control vs. hd high severity pgm/ml (p<. ). the p value between hd high severity vs. hd low severity group was <. . conclusion: elevated bnp is associated with severity, filling pressures, and active heart disease in the pediatric population. the sensitivity of the test appears to be stronger than the specificity. however, heart failure specific to the cavopulmonary connection does not appear to be associated with an elevated bnp. key words: bnp, heart failure, pediatrics vasodilatory shock after cardiopulmonary bypass in children: use of low-dose vasopressin. lechner e, mair r, tulzer g, fraser cd*, chang ac*, children's heart center linz *texas children's hospital. systemic vasodilation and severe hypotension can occur due to septic shock or from systemic inflammatory response after cardiopulmonary bypass. successful vasopressin -therapy of vasodilatory shock secondary to sepsis or systemic inflammatory response syndrome after cardiopulmonary bypass in adults has been reported previously. data on the use of vasopressin in children with vasodilatory shock, however, is very limited and indications as well as dosing have not been established. we want to report two cases, which demonstrate the successful and save use of vasopressin in the treatment of vasodilatory shock following cardiac surgery in children. the first case is a year-old male who developed vasopressor-resistant hypotension after cardiac surgery for endocarditis. as norepinephrine resulted in aggravation of the preexisting ventricular arrhythmia, vasopressin was used to maintain blood pressure. the vasopressin continuous infusion was started at . uaekg ) aemin ) and titrated up to . uaekg ) aemin ) . this low dose led to resolution of hypotension without causing side effects. the second case report is about a newborn that developed severe vasopressor-resistant vasodilatory shock following an arterial switch operation. vasopressin was started at an infusion rate of . uaekg ) aemin ) and minutes later increased to . uaekg ) aemin ) . this dose led to resolution of the hypotension and increased urine output within minutes. there were no side effects observed. in selected patients with vasodilatory shock after cardiac surgery, low-dose vasopressin seems to be a very potent agent compared to traditional vasopressors. (even when traditional vasopressors fail) since indications, dosing and duration of intravenous vasopressin therapy have not been established, its cautious use in children is recommended. often, due to the severity of illness and rapid deterioration, there is no opportunity to prepare or educate the child prior to implantation of the device. we wish to report our experience of helping pediatric patients adjust to the postoperative psychological and psychosocial impact of the device. methods: recognizing the importance of human growth and development, a multidisciplinary team worked with patients and families to increase familiarity with the device, encourage mastery, coping and expression of feelings. age and developmental level of the patients were considered and individual teaching plans were implemented. four categories of education emerged: breaking the news, living with the lvad, normalizing the experience, and preparing for transplant. beginning when the child emerged from anesthesia, the child life specialist and bedside nurse began explaining why the device was placed and its importance in their treatment. the child life specialist, with parental involvement, used ageappropriate materials to give the child an understanding of how the machine worked. pictures and mirrors were used to demonstrate how the device looked on their body. as patients recovered, the multidisciplinary team assisted patients and families manage life with the lvad. this included using distraction and guided imagery during daily dressing changes, pt/ ot therapies, ambulation, and transfer to the portable device to allow patients fewer restrictions and more mobility. normalizing the experience of living with an lvad is critical. a daily schedule was created including tutoring, participation in music and art therapy as well as cardiac rehabilitation in the exercise lab. visits to the ward and playroom with nursing staff were coordinated to foster peer relationships and to aid in social adjustment. results: since eight children have undergone lvad placement ( heartmate/ thoratec). median age at implantation was years (range to years). three were female and five were male. dilated cardiomyopathy existed in seven patients and ventricular tachycardia induced heart failure in one. one patient was bridged to recovery, five patients were successfully bridged to heart transplantation, one patient expired, and one is awaiting transplant. average duration of support on lvad was weeks (range of days to months). complications included bacteremia, endocarditis, cutaneous vad site infections, postoperative bleeding, and stroke. transition to the ward with the lvad was possible for five patients. school instruction was arranged for six patients and five attended school. all received child life services, art and music therapy, physical and occupational therapy. six patients participated in cardiac rehabilitation, four in the cardiac rehabilitation center. no intentional manipulation or disruption of lvad function occurred. working collaboratively with patients and families, the multidisciplinary team successfully helped patients cope and emotionally prepare for transplantation. conclusions: despite a lack of opportunity for preoperative teaching and preparation prior to placement of the lvad, pediatric patients can be successfully supported and can adjust with age appropriate and developmental educational strategies provided by a multidisciplinary care team. . adult pts requiring ventricular assist device (vad) support prior to ctx are at increased risk for high pra compared with pts not on support. purpose: we report one pediatric ctx centers experience with high pra in pts on vads. methods: we reviewed the histories of all pts who received pulsatile vad support between and . results: we identified pts, age to yrs (median yrs); pts were supported with heartmate and pts with thoratec vads. prior to vad, pra was negative to weakly positive for class i and class ii antigens in all pts. serial pras were obtained every - wks. all pts had multiple transfusions of red cells and other products during and after vad placement, averaging exposures per pt (range to ). four pts had infections requiring treatment while on vad support: candidemia ( ), candidal endocarditis ( ), pseudomonas bacteremia ( ), paronychia ( ) and cutaneous vad site infection ( ). two pts (both with thoratec vads) developed high pras: spontaneously resolved in wks; the other remained elevated to % class i and % class ii antigens, and received a favorable prospective cross match at ctx. this pt had intensive immunotherapy at induction and post-ctx with plasmapheresis, ivig, atg, steroids, tacrolimus, sirolimus and mycophenolate. despite these measures, the pt had x rej > a early post-ctx, treated with steroids and daclizumab; rej is now controlled and heart function is good. the average rej frequency for vad patients without high pra was . rej/pt/yr. of the pts, received ctx and are alive, pt awaits ctx, pt died while waiting, and pt recovered and vad was explanted. conclusions: pra elevation, in pediatric pts on vad support, occurs infrequently despite common post-vad complications including multiple transfusions and infections. prospective crossmatching may not protect against severe rej in pts with high pra. further study is necessary to determine specific immunologic contributions of underlying risk factors. key words: ventricular assist devices, heart transplantation, pediatrics, and panel reactive antibody. pulsatile ventricular assist devices (pvads) are commonly used in adults with end stage heart failure. experience with pvad support in children is limited. purpose: we report one pediatric cardiac transplant (ctx) center's experience with pvad support. methods: we reviewed the charts of all patients (pts) on pvad support between and . results: we identified pts, age to years (median yr, avg . yr) who received pvad therapy. weight ranged from to kg, pts were< kg. bsa ranged from . to . m , median . m . diagnosis in pts was dilated cardiomyopathy; pt had heart failure associated with ventricular tachycardia. vad inflow cannulation was via the left ventricular apex in pts, and via the left atrial appendage in pt. post-vad implant bleeding occurred in all pts, with an average of donor exposures (range, - units, all blood products including platelets, plasma, and cryoprecipitate) per pt. two pts required reoperation for bleeding. two pts developed early right ventricular failure on vad, but neither required bi-vad support. four pts had infections requiring treatment while on vad support: candidemia ( ), candidal endocarditis ( ), pseudomonas bacteremia ( ), paronychia ( ) and cutaneous vad site infection ( ). thromboembolic stroke occurred in pt. two pts developed elevated panel reactive antibody levels. no pt suffered vad malfunction. average time on vad was wks (range days to . months, median days). of the pts, received ctx and are alive, pt is awaiting ctx, pt died (of stroke) while waiting, and pt recovered and vad was explanted. kaplan-meier survival estimate was % at years post-vad insertion ( % confidence interval % to % survival at years). conclusions: pvad support can be used in pediatric pts as a bridge to transplant or to recovery. complications of pvad therapy are similar to those seen in adult pts. survival for pediatric pts on pvad is similar to, if not better than, that reported in adults. key words: ventricular assist devices, pediatrics, heart failure, and heart transplantation. background: an abnormal origin of the left main coronary artery from the pulmonary trunk (alcapa) causes chronic global left ventricular (lv) ischemia and secondary lv dysfunction. after coronary reimplantation, good recovery of lv function is generally described. however, few data are available on residual regional myocardial dysfunction. strain () (%) and strain rate (sr) ( /sec) imaging, derived by ultrasound allows quantification of regional myocardial function. methods: patients after alcapa repair were included. ventricular function was assessed by both standard echocardiographic indices and sr/ imaging. aim: to evaluate right ventricular (rv) and lv longitudinal and radial function in alcapa patients late after repair (> year) and to compare these data with age comparable healthy children. results: lv and rv dimensions as well as lv fractional shortening were within normal range. mitral ring displacement was reduced for both lateral and septal motion (p < . ). tricuspid ring displacement was normal. radial function in alcapa patients was normal as assessed by ultrasonic /sr imaging (patients: = ± ; sr = . ± . vs. normals: = ± ; sr = . ± . , p = ns). regional longitudinal function, assessed by /sr imaging, was significantly reduced in alcapa patients (p< . ). this reduction was homogeneous for each wall studied. rv regional deformation assessed in the rv free wall was normal. conclusions: late after coronary reimplantation, lv longitudinal function remains significantly reduced in alcapa patients while regional radial function completely normalizes. prolonged chronic global ischemia may have produced local subendocardial fibrosis selectively impairing long axis function. long-term consequences of reduced long-axis function must be followed. this study examines the use of ultrasound-based strain and strain rate imaging for detecting early regional changes in myocardial function in patients with duchenne muscular dystrophy (dmd). we examined dmd patients aged . ± . years (range to years). data were compared with measurements in age-matched normal controls (mean age . ± . years, range - years). both standard gray-scale echocardiographic measurements as well as doppler myocardial imaging data were obtained. doppler myocardial velocities, peak systolic strain rate and strain were estimated both in the radial (inferolateral wall) and longitudinal directions from the lv lateral wall, interventricular septum and rv lateral wall. standard scale-scale ultrasound indices of left ventricular function (e.g. fractional shortening; diastolic function parameters, etc.) were not different in the patient group compared to normal controls. myocardial tissue velocities were only significantly reduced in the lv lateral wall. a highly significant decrease in radial peak strain rate and strain was found in the inferolateral wall (sr . ± . )s vs. . ± . -s , p < . strain ± vs. ± , p < . ). longitudinal strain rate was also reduced in the lv lateral wall () . ± . )s vs. - . ± . )s , p < . ) but not in the interventricular septum. longitudinal strain was significantly reduced in the lv lateral wall () ± vs. - ± , p < . ) as well as in the interventricular septum (- ± vs. - ± , p < . ). the doppler myocardial imaging parameters measured in the rv lateral wall were normal. we conclude that by using strain rate and strain imaging in young duchenne patients a decrease in deformation parameters can be observed especially in the lv inferolateral wall. this suggests early cardiac involvement in the disorder. this has possible implications for the medical treatment of this patient group. moreover the technique has the potential to be used in clinical practice for detecting early myocardial dysfunction. purpose: levosimendan (ls) is a novel cardiovascular drug for the treatment of heart failure. ls improves myocardial contractility without causing an increase in myocardial oxygen demand. ls sensitizes troponin c to calcium, thus improving contractility. this sensitization is lost during diastole, allowing normal or improved diastolic function. ls also leads to vasodilatation through the opening of atp-sensitive potassium channels. the maximum recommended dose for intravenous administration is a bolus dose of - lg/kg followed by an infusion of . lg/kg/min for hours in adults. the intravenous formulation of ls is indicated for short-term treatment of acutely decompensated severe chronic heart failure in adults. the purpose of this study is to evaluate our initial experience of ls in pediatric cardiac patients. methods: patient data and dosing by september th , ls has been given to patients in our hospital, - times per patient, total amount of times. data of patients is presently included in this study. / patients received ls after cardiac operation or during weaning from perfusion. / patients had dilated cardiomyopathy and have received several doses of ls. one patient with earlier operated fontan received ls for acute heart failure. one patient with previously transplanted liver received ls for pulmonary hypertension. the mean age of the post operatively treated group was . years (range . - . ) and the mean age of the cardiomyopathy group was . years (range . - . ). the post op group received mean of . infusion (range - ) and the cardiomyopathy group mean of . infusions (range - ). all patients had other vasoactive drugs parallel with ls. loading dose of lg/kg was given in / treatments. infusion of . - . lg/kg/ min was given following the loading dose. results: a loading dose of lg/kg followed by an infusion of . to . lg/kg/min for h was well tolerated. most patients had no clinically important effect on blood pressure or heart rate. however, / patients had mild hypotension, / mild headache and / sinus tachycardia. all these patients were from the cardiomyopathy group. / patients died with no connection to levosimendan treatment. of these patients were from the postoperative group and one with late heart failure after fontan operation. ls was used for weaning from cardiopulmonary perfusion in patients, with a failure to wean with normally used inotropes. / patients were weaned successfully after initiation of ls treatment, / patients were converted to left ventricular assisting device (lvad). both of these patients were weaned from lvad with ls. conclusion: early experience of ls in children after cardiac surgery or dilated cardiomyopathy indicates that ls is well tolerated. however, prospective pediatric studies are needed to evaluate possible advantages of ls compared with currently used vasoactive drugs. key words: levosimendan, heart failure, cardiomyopathy methods: children were studied, age range from to months (median . months). the ted transducer emitting a -mhz continuous wave doppler signal was introduced orally and advanced until the characteristic descending aorta waveform was obtained on the monitor (edm ii, deltex ltd, chichester, uk). seven consecutive values of minute distance (md) were calculated and the mean taken. simultaneously the heart rate, mean blood pressure, central venous pressure and lab variables such as base deficit (arterial blood gas analysis) and blood lactate were measured and the mean for consecutive values was taken for each parameter. following a fluid challenge, seven repeat pairs of measurement were made. results: scatter plot of the mean percentage difference of md against the other variables showed that there was minimal degree of linearity between the heart rate, mean blood pressure, lactate level and base deficit for the difference pre and post fluid infusion. however central venous pressure percentage difference showed more marked negative linearity. linear regression univariate analysis showed that there was no correlation between md and heart rate, mean blood pressure, lactate level and base deficit. in the case of central venous pressure percentage changes there was a definite correlation but with borderline significance (p = . ). our ted data showed consistent values with excellent reproducibility, confirming the accuracy of the technique. conclusions: clinical and laboratory assessment of hemodynamic status is not always reliable in critically ill children. it is therefore important to have an accurate estimate of cardiac output using a noninvasive technique such as ted, which avoids the risks associated with pulmonary artery catheterization. introduction: levosimendan is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of atp-dependent potassium channels. unlike inotropic drugs (b adrenergic agents and phosphodiesterase inhibitors) these drugs improve cardiac performance without intracellular calcium and camp elevation. patients and methods: we show our first two patient experience using levosimendan in our cicu. data was obtained from the patient's medical charts. intravenous loading dose was mcg/ kg, followed with a continuous infusion of . - . mcg/ kg/ min during a -hour period. clinical response was estimated through the patient's clinical condition and continuous monitoring, including heart rate and rhythm, cvp, invasive ap, urine output, arterial lactic acid and acid-base status, together with mechanical ventilation (mv) requirements and daily blood creatinine. informed consent was obtained from both parents. case : twelve-month-old girl, with diagnosis of dilated myocardiopathy, waiting for cardiac transplantation. referred to our unit from another institution, she was admitted in severe cardiac failure in spite of a dopamine infusion of mcg/ kg/ min. milrinone was added without any significant clinical improvement. ten days after she progressed to cardiogenic shock and multiple organ dysfunction. mv together with peritoneal dialysis (pd) and an epinephrine infusion ( . mcg/ kg/ min) were started. twelve hours later she was still hemodynamically unstable and levosimendan was introduced in the aforementioned doses. forty-eight hours later the girl had improved significantly, being hemodynamically compensated, requiring less mv pressures and with a normal diuretic response, without any pd requirements. levosimendan was re-infused days later, allowing the patient to get her heart transplant days after the infusion. case : five-year-old girl with l-tgv, multiple vsd (perimembranous and apical) and pulmonary atresia. she had undergone two previous b-t shunts (right and left, at age days and years). she also had light systemic a-v valve insufficiency. a rastelli surgical procedure was performed. pos-op she developed a severe low cardiac output syndrome progressing to a multiple organ dysfunction requiring mv, epinephrine and milrinone infusions. seven days later she was extubated but had to be reintubated hours later. cardiac catheterization was performed which showed no significant residual defects but little muscular vsd (qp/ qs . / ). end diastolic pressure was high in both ventricles ( mm hg). levosimendan was started using usual doses. forty-eight hours later she was successfully weaned from the ventilator, and discharged home a week later. follow up shows nyha class i -ii. conclusion: our short experience with the use of levosimendan shows a satisfactory clinical response, successfully bridging a patient to undergo cardiac transplantation in one patient, and helping in weaning a patient from mv and consequently discharging her home. more studies are needed in order to confirm levosimendan´s usefulness in congestive heart failure in children. cardiac transplantation is the end result of treatment of heart failure in many affected children. despite good early survival following heart transplantation in children, death or re-transplantation may occur from a variety of reasons including graft failure (gf) due to acute and chronic rejection. late gf in the pediatric heart transplant recipients is of great concern due to the reasonable expectation of greater longevity for these patients. the time related incidence of gf defined as death or retransplantation due to primary graft dysfunction, acute rejection, or chronic rejection has not been examined in pediatric patients. we hypothesized that the probability of gf would increase over time due to chronic rejection with graft atherosclerosis. methods: data from the centers participating of the pediatric heart transplant study was analyzed to determine the incidence of gf over time and risk factors for gf. all patients ranging in age from to years who underwent transplantation from jan. , , through dec. , were included in the analysis. actuarial and parametric methods were used to determine time-related incidence of gf. recipient and donor variables were included in both a univariate and multivariable risk factor analysis. results: patients underwent transplantation with patients dying and requiring re-transplantation for gf. freedom from gf was % at one year, % at years, and % at years. parametric survival analysis demonstrated an early phase and an accelerating late phase of risk for gf. the late phase was most apparent in recipients greater than yrs of age at transplant with % freedom from gf at years post transplant compared to % for recipients less than yrs of age at transplant. this late phase of accelerating risk was not seen in infants transplanted at less than mos. risk factors for early graft failure included younger patient age at transplant, failure to use induction therapy, and longer ischemic. late phase risk factors were older patient age at transplant, black recipient race, and previous cardiac surgery. black recipients were nearly twice as likely to die of graft failure by years post transplant compared to white and hispanic recipients. conclusions: almost one third of pediatric heart transplant recipients will experience gf within yrs of transplant. the presence of a late phase of accelerating gf is an important limitation on survival following heart transplantation in children. the absence of a late phase for gf in infants may reflect the development of graft tolerance in this group. late gf is more likely in older patients and black recipients. high-risk groups warrant enhanced rejection surveillance and immunosuppression to prevent gf due to acute and chronic rejection. background: information on myocardial remodeling in pediatric heart disease is sparse. our aim was to study whether expression of the cardiac sarcoplasmic reticulum ca +-atpase (serca) and phospholamban (plb) is different in volume overloaded compared to not overloaded atrial myocardium and wether this is different in younger vs. older patients. methods: rt-pcr was used to measure mrna expression of serca and plb in atrial myocardium from pediatric patients with volume overloaded right atrium and patients with not overloaded atria. results: amount of transcripts was expressed as mrna molecules per s rrna molecules. in the entire group serca mrna was lower in the volume overloaded (vo, ± ) compared to the not overloaded (no) atrial myocardium ( ± , p = . ). there was no more difference if only the patients older than (n = ) months of age were compared (vo group ± vs. ± in the no group, p = . ), in the younger patients (n = ) there was still a significant difference (vo group ± vs. ± , p = . ). the plb mrna did not differ between vo ( ± ) and no group ( ± , p = . ), again, there was a tendency to lower mrna expression in the vo group ( ± ) vs. the no group ( ± , p = . ) if only patients under months of age were investigated. comparing the overall group regardless of hemodynamic overload in regard to age no statistical significant difference was found between patients older than months of age vs. patients younger than months of age, neither for serca (p = . ) nor for plb (p = . ). conclusions: in this study we could show a significant difference of serca mrna expression in volume overloaded atrial myocardium only in patients younger than months of age, also for plb there was a tendency to diminished mrna expression only in the younger patient group. this is in contrast to former reports comparing pressure overloaded ventricular myocardium in sheep (aoyagi t et al., ped res, , : - ) , which showed reduced serca mrna only in adult sheep. these results are of importance as we know of age dependent differences in expression of serca in different species and in the neonate, however this study is the first investigating the combined influence of age and hemodynamic overload on pediatric atrial myocardium. as molecular changes in animal and even in adult human cardiac disease can not be adopted to the situation in infants and young children this paper adds further insights in in pediatric cardiac disease. purpose: myocardial ischemia-reperfusion (ir) stimulates the activity of cysteine proteases called calpains. calpain activity is associated with interruption of calcium-regulated contraction, degradation of contractile proteins, and enhanced cell death. immature myocardium has been shown to have elevated levels of calpain suggesting an enhanced role in neonatal ir. we hypothesized that calpain inhibition could reduce myocardial injury during ir. methods: a model of deep hypothermic circulatory arrest with cpb (dhca-cpb) was utilized. eight neonatal piglets (controls) were cooled to °c on cpb, underwent hours of dhca, re-warmed, and recovered for hours. hemodynamics were monitored and myocardial tissue analyzed for activation of nf-kb and pro-death pathways. an additional animals received mg/kg of the peptide calpain inhibitor (z-leu-leutyr-fmk) hour before cpb and dhca. results: oxygen delivery was significantly depressed in controls at end-recovery ( +/) ml/min), but was maintained in treated animals ( +/) ml/min, p <. ). calpain activity was decreased in treated animals compared with controls ( +/) vs. +/) fluorescent units, p <. ) calpain inhibitor animals had higher ikb protein levels ( . +/) . vs. . +/) . ikb/gapdh protein ratio, p <. ), and decreased nf-kb activity ( +/) vs. +/) densitometry units, p <. ) at end-recovery compared to controls. treated animals also demonstrated less bid cleavage and decreased caspase activity compared with controls: +/) vs. +/) . expressed as % kd of total bid protein, p <. ; and . +/). vs. . +/). devdase activity, p <. , respectively. conclusions: calpain inhibition resulted in maintenance of ikb and decreased nf-kb activity, which would be expected to correlate with decreased acute injury, and improved function as evident by improved oxygen delivery. decreased bid cleavage and decreased caspase activity were evident with calpain inhibition, which along with decreased nf-kb activity would likely correlate with a decrease in apoptosis and hence, decreased permanent myocardial injury. calpain inhibition decreases both acute and permanent myocardial ischemia-reperfusion injury through at least two separate pathways. background: magnetic resonance imaging (mri) facilitates a true simpson's rule approach to determination of ventricular volume indices, an approach that does not depend on geometric assumptions often invalid in the presence of cardiomyopathy. however, evaluation of cardiovascular function with mri has previously required prolonged imaging times. prolonged studies are particularly difficult for pediatric patients. purpose: to determine the feasibility of performing rapid assessment of ventricular function by mri in a pediatric population with known or suspected dilated cardiomyopathy. methods: twenty-five unsedated pediatric patients (ages - yr, m = ± . ) underwent ventricular functional evaluation with a balanced fast field echo mri technique. parallel data acquisition with sensitivity encoding (sense) technique was employed with sense of . sequence parameters were te/tr = . ms/ . ms, flip angle °, slices. studies were performed on a phillips . tesla scanner. a real-time interactive method was employed to achieve true short axis positioning of the contiguous slices. vectorcardiographic electrocardiographic synchronization of the measurement sequences was utilized. free breathing (free) mri ventricular functional assessment was compared to mri assessment during very short (less than second) sequential breath holds (bh). a computer assisted simpson's rule technique was employed to calculate left ventricular end systolic (lvesv) and end diastolic (lvedv) volumes, ejection fractions (lvef), and mass (lvmass) from the mri data. two-dimensional echocardiographic (echo) measurements of these parameters were performed for correlation using a biplane method. results: actual mri cardiac volume data acquisition time was less than seconds in each case. denfield, m.d , , ., department of pediatrics (cardiology), texas children's hospital and texas heart institute, houston, tx. background: advanced heart failure in children is associated with high morbidity and mortality and is often refractory to standard medical therapy. acute exacerbations of chronic decompensated heart failure can be successfully ameliorated by the use of parenteral inotropic therapy (pit); however, its use in children in the outpatient setting has not been described. the purpose of this study was to review our institutional experience with the use of outpatient pit for advanced heart failure in children as bridge to transplant. methods: we performed a retrospective review of our medical records for all patients treated with pit as outpatients. results: seven patients received outpatient pit from / to / (male = , female = , mean age = . years ± . ). etiology of heart failure included idiopathic dilated cardiomyopathy (n = ), congenital heart disease (n = ) and ischemic cardiomyopathy (n = ). all patients were listed for cardiac transplantation. inotropic medications used included dopamine alone (n = ), milrinone alone (n = ) and dopamine and milrinone in combination (n = ). mean dose of dopamine was . mcg/kg/min ± . . mean dose of milrinone was . mcg/kg/min ± . . therapy was initiated as inpatients. doses were not adjusted during outpatient therapy. median duration of therapy was weeks (range to weeks). the mean number of emergency department visits per patient was greater before starting pit than after starting pit for the same duration of time ( . ± . vs . ± . , p = . ). the mean number of hospital admissions per patient was greater prior to therapy than after starting therapy ( . ± . vs. . ± . , p = . ). the mean ef% in patients with systolic dysfunction improved while on therapy ( ± % before vs. ± % after, p = . ). there was death and complications in patients. the mortality occurred suddenly at home. complications included catheter occlusion (n = ), extravasation of catheter (n = ) and line infection (n = ). six patients underwent transplantation. conclusions: these data show that continuous parenteral inotropic therapy can reduce the frequency of emergency department visits and hospital admissions and improves ventricular systolic function in children with advanced heart failure. the mortality rate did not exceed the reported frequency of death in patients awaiting cardiac transplantation. key words: heart failure, outpatient, and inotropic therapy congestive heart failure is still a major health problem in pediatric patients. it is a complex syndrome with various neuro-hormonal and neuro-humeral activation. some investigators found that cytokines as tumor necrosis factor alpha and interleukin- are elevated in adult cases of congestive heart failure due to ischemic and cardiomyopathic heart failure; others mentioned that they are elevated in heart failure whatever the etiology of heart failure. we aimed to determine the serum level of one of these as il- in cardiomyopathic heart failure and rheumatic heart disease with heart failure and to detect the correlation between its serum level with functional stage of heart failure, cause of heart failure and left ventricular systemic dysfunction. we conducted a study involving of heart failure ( cardiomyopathic and rheumatic heart disease) matched with healthy control group in the same age range. cases and controls were subjected to history taking particularly for duration of illness, anthropometric measures, clinical assessment especially for stage of heart failure, echocardiography and measurement of serum level of il- using elisa test. we found that serum level was significantly higher in cases ( . ± . sd ng/dl) than in control group ( . ± sd ng/dl), significantly higher in rheumatic ( . ± . sd ng/dl) versus cardiomyopathic ( . ± . sd ng/dl) heart failure, no significant correlation with left ventricular systolic dysfunction, age, sex or esr. there was significant correlation between functional class of heart failure and the serum level of il . serum level of il was significantly higher in cases of heart failure with shorter duration (< months, mean serum il was . ng/dl)) than those with longer duration (> months mean serum il level was ng/dl). we concluded that il- is significantly elevated in heart failure and the plasma concentration of il- may be a clinically useful prognostic marker for longterm survival. methods: cases of tof (age . ± . ) who underwent corrective procedure were selected. patients were divided into two groups according to the inotropic agents administrated, dopamine or milrinone. cardiac index (ci), the mixed venous oxygen saturation (svo ), systemic and pulmonary vascular resistance index (svri, pvri) were estimated by the thermodilution method at , , , hours after operation. the data of h post-operation was considered as the baseline. results: hours after surgery, cardiac index (ci) decreased . % and . % in dopamine group and milrinone group respectively, compared with the baseline value (p < . , p < . ). hours after surgery, ci of both groups had no difference compared to the baseline values (p > . ). milrinone group had higher ci(p < . ) and lower svri, pvri (p < . ,p < . ) than dopamine group (tab. ). conclusion: tendency of lco will happen with different extent in the early post-operative period of tof. using milrinone, a phosphodiesterase-iii (pde-iii) inhibitor will benefit to prevent and treat the postoperative lco. amineva kh, gudkova a, shlyakhto e. and sejersen t,, karolinska institutet, stockholm, sweden during the past years mutation of several structural and sarcomeric proteins have been identified as causes of cardiomyopathies. among these, desmin are associated with dilated and restricted cardiomyopathies. desmin is implicated in the sarcomeric organisation, and, being associated with z-bands and intercalated disks, presents a key structure of the cytoskeleton in muscle cells. recently, we reported a desmin mutation, transmitted over several generations. this l p missense mutation has a dominant-negative effect on filament formation, causing myopathy and cardiomyopathy. a transgenic mouse strain (dm), carrying the desmin l p mutation, was developed in order to evaluate the effect of this mutation on cardiac and skeletal muscle pathology and function. transgenic animals with normal desmin gene were used as a control (ds mice). expression of transgenic desmin was confirmed by immunohistochemistry and western blot analysis using ha-tag antibody. here, we present data on morphological and functional analyses of heart muscle in dm and ds animals. results: in week old dm mice an increase of stromal cell number, due to lymphocyte and fibroblast-like cell infiltration, was observed. cardiomyocytes, embedded in collagen fibers, and focal amorphic protein depositions in arterial adventitia and perivascular spaces were often found. in week old dm mice these depositions were more prominent, being present in vascular walls, perivascular space and between muscle fibers. the latter were accompanied by granuloma formations, and caused a disruption of tissue architecture. histiocyte-like and macrophage-like cells were observed in perivascular and intermyocyte spaces. enlarged cardiomyocyte nuclei contained - nucleoli. in some myocytes perinuclear vacuolisation were observed. degree of cardiomyocyte disarray varied from mild to moderate, being more prominent in areas of fiber disruption and protein depositions. in these areas cardiomyocyte nuclei were enormously big, containing - nuclei. most of these changes were not found in ds mice, except slight variation of nuclear size and microfoci of protein depositions. conclusions: the l p desmin mutation causes focal protein deposition in vascular walls, perivascular areas and intermyocyte spaces, accompanied by an increase in stromal cell numbers and formation of granulomas. these changes may be responsible for the development of desmin-related cardiomyopathy. remarkable progress has been made over the last years on ventricular assist devices (vad) for adults with failing ventricle. but only small series describe vad as a system to keep children with otherwise intractable heart failure alive until myocardial recovery or transplantation. the berlin heart: consists of extracorporeal pneumatically driven blood pumps made out of polyurethane ( , , , , , ml stroke volume), within a multi-layer flexible polyurethane membrane separating this pump-chamber into a blood and an air chamber. three-leaflet polyurethane valves in the small and mechanical valves in the larger pumps prevent blood reflux. four silicon cannulae connect the blood pumps with the right atrium and pulmonary artery, and the left atrium or apex and ascending aorta. a dacron cover in the middle part of the cannulae allows a rapid ingrowth of patient's tissue as a biologic barrier against ascending infections. the pumps are driven by a pulsatile electro pneumatic system, all bloodcontacting surfaces are heparin-coated. the drive units (ikus and heimes hd ) are both with complete back-up. patients: in children, age days - years (median y), artificial replacement of heart function with vad (berlin heart) had been applied for long-term support ( - , mean days) to offer life-saving support in our hospital between and july . twenty-five had lvad support and were on bvad. they all were in cardiogenic shock with multiorgan failure, with fulminant myocarditis, cardiomyopathy without surgery before, chronic stage of congenital heart disease and in weaning from bypass had failed after surgery. six children were weaned from the system, reached heart transplantation, died on vad and one is still on the system. the overall survival of the myocarditis group is % and survival of the children with cardiomyopathy is %. causes of death were loss of peripheral circulatory resistance, multiorgan failure and shock ( ), hemorrhagic and thromboembolic complications ( ) and one brain death. the problems were thrombosis, bleeding and rethoracotomy. there were no severe problems with infection of the system or pump dysfunction. one child has mild cerebral residuals after cerebral infarction; the other survivors are without sequel. conclusion: prolonged circulatory support with vad is an effective method for bridging until cardiac recovery even in newborns and small children. it offers time to restore organ function. extubation, mobilisation and enteral nutrition is mostly successful and if no spontaneous improvement occurs, vad increases the chance for transplantation. compared to ecmo, ventricular assist devices can be used in with low device related morbidity and satisfying results in the myocarditis and the cardiomyopathy group. background: mechanical support with a pulsatile pneumatic ventricular assist device is a complex rescue procedure performed in children with untreatable cardiogenic shock. its impact on early and long-term survival after subsequent heart transplantation remains to be determined. methods: we reviewed retrospectively the course of children (median age years, range days - years, body weight kg, range - kg) with heart transplantation. the elective-htx group (a) consists of children who were treated as outpatients before transplantation. the emergency-htx group (b) comprises children who were critically ill and in hospital before transplantation but without a ventricular assist device, whereas the vad-htx group (c) consists of children resuscitated and supported with a pulsatile pneumatic ventricular assist device for a median time of days. results: overall actuarial survival after cardiac transplantation was % at month, % at year, and % at years without significant differences between the three subgroups. group a had the best long-term survival rate with / / %, b had a survival rate of / / % and c / / %. there were no differences in neurological outcome, acute cardiac rejections or transplant failure. the survival rate was significantly better in the children with cardiomyopathy compared to those with congenital heart defects (p = . ). conclusions: bridging to heart transplantation by pulsatile pneumatic assist device is a safe procedure in pediatric patients. after heart transplantation overall survival of these children is similar to that of patients who were bridged with inotropes, or were electively awaiting heart transplantation. background: in its most severe forms, cellular rejection in the heart transplant patient may present with severe cardiac failure, cardiac arrest or multiple organ failure. we present a case of acute rejection causing such problems in a -year-old female, managed with veno-arterial (va) ecmo. case report and methods: a -year-old female patient presented to our regional cardiothoracic center with complaints of increasing shortness of breath and lower abdominal pain. she had undergone cardiac transplantation months previously for acute myocarditis, and was receiving tacrolimus/azathioprine immunosuppression. echocardiogram showed a significant pericardial effusion. she underwent general anesthesia for drainage of effusion and endomyocardial biopsy. during this she developed complete heart block requiring multiple cardiopulmonary resuscitation episodes and temporary pacing. she was then transferred, ventilated, to the pediatric intensive care unit (picu). she subsequently developed a low cardiac output state that required escalating inotropic therapy, accompanied by acute renal failure and hepatic dysfunction. she was given pulsed methylprednisolone therapy, as the biopsy showed acute rejection. in order to achieve hemodynamic stability and prevent progression of her multiple organ failure she was placed onto va+v ecmo, via surgically placed f right internal jugular vein cannula, f right common carotid artery cannula and f right femoral vein cannula. she was heparinized to an activated clotting time of - seconds. pump flow was . l/min ( ml/kg/min). a minntech hemofilter allowed hemodialysis. we used a medos oxygenator. inotropic support was subsequently rapidly weaned. there were no ecmo-related complications. total duration of ecmo was hours. this allowed anti-thymocyte globulin (atg) immunosuppression. ecmo was weaned with a modest dose of inotropic support. the patient was transferred to the ward after picu days (total duration of mechanical ventilation days). her cardiac function remains borderline (echocardiogram shows % fractional left ventricular shortening). conclusion: ecmo has been used in other centers under similar circumstances but this is to our knowledge the first description of such a case in the literature. our patient progressed rapidly from non-specific symptoms to multiple organ failure as a result of acute rejection and cardiac arrest. although her condition was potentially reversible by prompt aggressive immunosuppressive therapy, this takes some days to take effect. the pace of her deterioration suggested to us that mechanical circulatory support would be required as a bridge to recovery. it is our opinion that the use of ecmo arrested the progression of her multiple organ failure pending cardiac recovery. al throckmorton , a untaroiu , pe allaire , hg wood , db olsen , university of virginia, charlottesville, va, usa utah artificial heart institute, salt lake city, ut, usa. purpose: extracorporeal membrane oxygenation (ecmo), balloon pumps, and pediatric cardiopulmonary bypass (cpb) devices, which are intended for short-term use (less than weeks at most), represent the only pediatric mechanical circulatory support options for infants, children, and young adults awaiting heart transplantation. the majority of these pediatric patients suffer from cardiomyopathy and congenital heart defects, often complicated by congenital heart disease. since donor organ waiting periods may be as long as months in some cases, these patients could benefit tremendously from the availability of a mechanical circulatory support device for longer-term, bridge-to-transplant (btt) situations. in order to provide a viable, longer-term btt option for these patients, we have designed an implantable axial flow pediatric vad (pvad) with an impeller that is fully suspended by magnetic bearings. this pvad is a geometrically smaller scaled version of our adult axial flow pump and has a design point of . lpm to deliver mmhg at rpm. this pump's design has been refined and optimized with consideration for rapid prototype manufacturing and magnetic suspension / motor component placement. methods: conventional axial pump design equations with non-dimensional scaling provided initial pump dimensions. a computational model of the pvad was created and analyzed under steady state flow conditions for rotational speeds of to rpm using these dimensions. state-of-the-art computational fluid dynamics (cfd) software enabled several stages of optimization to ensure performance and minimization of irregular flow patterns. results: cfd analysis of the optimized axial flow pvad, which measures approximately mm in length by mm in diameter, predicts the pump will produce . lpm at mmhg for a rotational speed of approximately rpm. fluid forces exerted on the rotor under steady state conditions were also estimated to be approximately newton, and the fluid efficiency was calculated to range from % to %, which are typical values for blood pumps. scalar stress estimations throughout the fluid field were performed with levels remaining below pa with short residence times. conclusions: this optimized design illustrated excellent performance and will be the basis for prototype manufacturing and extensive experimental validation. prototype manufacturing will also facilitate initial, acute animal implant experiments. akintuerk h, valeske k, schranz d, children's heart center, university of giessen/germany elevated pulmonary vascular resistance (pvr) secondary to left heart failure and pulmonary venous hypertension may cause donor right heart failure after orthotopic heart transplantation. we report of children with elevated pvr, who were placed on ecmo immediately after htx as a prophylactic treatment against right heart failure. patients: age at htx: , , months. diagnoses: aortic stenosis with endocardial fibroelastosis ( ), dilated cardiomyopathy ( ). preop. pvr index: . , . , . wuxm , pvr/svr-ratio . , . , . . inhalative prostacyclin reduced pvr only in of children. results: ecmo-duration: , , hrs. weaning with inhalative-no, iv-prostacyclin and inotropic support. pap/sapratio after ecmo-expl.: . , . , . . pvr index months after htx: . , . , . wuxm . uneventful follow up over , , months. discussion: ecmo allows the right ventricle to recover from ischemic disorder following htx and to adapt to elevated pulmonary pressures. in young children a marked reduction of elevated pvr due to left heart failure could be expected after htx. failing response to inhalative prostacyclin in the preoperative testing does not exclude this change in pvr. the level at which pvr becomes an absolute contraindication against htx in children remains unknown. conclusion: with prophylactic use of ecmo htx is feasible in children with highly elevated pvr. children's heart center, university giessen/germany comparative evaluation of clinical experience with ecmo (centrifugal pump, biomedicus) and the medosÒ-vad (displacement pump, pulsatile flow). months); postcardiotomy , primary organ failure after htx , prophylactic ecmo after htx in children with elevated pvr , rescue-ecmo in cardiac shock . vad: n = results: ecmo: duration - d (median . days); complications: bleeding , sepsis , thromboembolic , myocardial infarction background: isolated ventricular noncompaction (ivnc) to measure noncompacted:compacted segment ratio, left ventricle (lv) size, ejection fraction (ef), and tei index, both at presentation and at most recent visit. medical records, electrocardiograms, holter recordings and heart rate variability (hrv) data were also reviewed. results: twenty-words: isolated ventricular noncompaction, cardiomyopathy, heart failure urine output increased from cc/kg/hr to cc/kg/hr with discontinuation of the intravenous furosemide infusion. serum sodium increased to , bun decreased to , and serum creatinine decreased to . . the minimum dose of nesiritide was utilized through the entire course with no titration being necessary. serum monitoring of bnp demonstrated elevated bnp levels prior to starting the infusion. the levels increased appropriately with infusion and decreased to below baseline following infusion discontinuation. it was also noted that hypertensive blood pressure control improved with weaning from vasoactive drips being accomplished while on nesiritide infusion. conclusions: nesiritide was safely administered to a sick pediatric orthotopic heart transplant patient. the favorable effects noted were compensation of heart failure, improvement of renal function, and correction of hyponatremia. no hypotension or arrhythmias were noted. nesiritide was administered concomitantly with intravenous vasoactive medications without difficulty and allowed for the wean and discontinuation of these medications that have inherent side effects relating to blood pressure and arrhythmogenicity. nesiritide may become another option for the safe and efficacious treatment of decompensated heart failure or post-operative complications in the pediatric population. key words: nesiritide, heart failure, pediatric he developed hemodynamic compromise on post-operative day and had evidence of humoral rejection on endomyocardial biopsy. he was treated with a steroid pulse ( mg x and x ) and plasmapheresis therapy for a total of consecutive days followed by high dose ivig. he was also maintained on an immunosuppression regimen of neoral ( . mg/kg/day divided every hours), prednisone ( . mg/kg/day), and cyclophosphamide ( mg/kg/ day) key: cord- - t ai e authors: pappalardo, federico; pieri, marina; greco, teresa; patroniti, nicolò; pesenti, antonio; arcadipane, antonio; ranieri, v. marco; gattinoni, luciano; landoni, giovanni; holzgraefe, bernhard; beutel, gernot; zangrillo, alberto title: predicting mortality risk in patients undergoing venovenous ecmo for ards due to influenza a (h n ) pneumonia: the ecmonet score date: - - journal: intensive care med doi: . /s - - - sha: doc_id: cord_uid: t ai e purpose: the decision to start venovenous extracorporeal membrane oxygenation (vv ecmo) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. the aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of vv ecmo initiation. methods: this was a prospective multicenter cohort study on patients with influenza a (h n )-associated respiratory distress syndrome participating in the italian ecmonet data set in the pandemic. criteria for ecmo institution were standardized according to national guidelines. results: the survival rate in patients treated with ecmo was %. significant predictors of death before ecmo institution by multivariate analysis were hospital length of stay before ecmo institution (or = . , % ci . – . , p = . ); bilirubin (or = . , % ci . – . , p < . ), creatinine (or = . , % ci . – . , p = . ) and hematocrit values (or = . , % ci . – . , p = . ); and mean arterial pressure (or = . , % ci . – . , p < . ). the ecmonet score was developed based on these variables, with a score of . being the most appropriate cutoff for mortality risk prediction. the high accuracy of the ecmonet score was further confirmed by roc analysis (c = . , % ci . – . , p < . ) and by an independent external validation analysis (c = . , % ci . – . , p = . ). conclusions: mortality risk for patients receiving vv ecmo is correlated to the extrapulmonary organ function at the time of ecmo initiation. the ecmonet score is a tool for the evaluation of the appropriateness and timing of vv ecmo in acute lung failure. electronic supplementary material: the online version of this article (doi: . /s - - - ) contains supplementary material, which is available to authorized users. abstract purpose: the decision to start venovenous extracorporeal membrane oxygenation (vv ecmo) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. the aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of vv ecmo initiation. methods: this was a prospective multicenter cohort study on patients with influenza a (h n )-associated respiratory distress syndrome participating in the italian ecmonet data set in the pandemic. criteria for ecmo institution were standardized according to national guidelines. results: the survival rate in patients treated with ecmo was %. significant predictors of death before ecmo institution by multivariate analysis were hospital length of stay before ecmo institution (or = . , % ci . - . , p = . ); bilirubin (or = . , % ci . - . , p \ . ), creatinine (or = . , % ci . - . , p = . ) and hematocrit values (or = . , % ci . - . , p = . ); and mean arterial pressure (or = . , % ci . - . , p \ . ). the ecmonet score was developed based on these variables, with a score of . being the most appropriate cutoff for mortality risk prediction. the high accuracy of the ecmonet score was further confirmed by roc analysis (c = . , % ci . - . , p \ . ) and by an independent external validation analysis (c = . , % ci . - . , p = . ). conclusions: mortality risk for patients receiving vv ecmo is correlated to the extrapulmonary organ function at the time of ecmo initiation. the ecmonet score is a tool for the evaluation of the appropriateness and timing of vv ecmo in acute lung failure. extracorporeal membrane oxygenation (ecmo) is a valuable therapeutic option for patients with acute lung failure [ ] . during the h n influenza a pandemic, the use of venovenous (vv) ecmo represented a successful rescue treatment for acute respiratory distress syndrome (ards) in patients failing conventional ventilation techniques [ ] . due to its additional costs and the need for trained expertise, however, a rational allocation of this limited resource is of fundamental importance. referral and transfer of patients with h n -related ards to specialized ecmo centers have been shown to be associated with a lower risk of death compared to non-ecmo-referred patients [ ] . currently, the decision to start ecmo is based on commonly used pulmonary scores assessing the severity of respiratory failure, such as murray's acute lung injury score and the oxygenation index. a murray score [ was used for enrollment and randomization in the ''conventional ventilation versus ecmo for severe adult respiratory failure'' (cesar) trial [ ] , as it identifies severely hypoxemic patients failing protective mechanical ventilation with an estimated mortality risk higher than % in comparison to conventional treatment. oxygenation failure, however, is rarely the direct cause of death in ecmo patients. on the contrary, a poor outcome is more likely to be determined by the presence of complications [ ] . besides bleeding complications, most directly linked to the procedure itself, the most common causes of death are related to non-protective mechanical ventilation or to infectious or non-infectious inflammation [ ] , leading to various degrees of organ dysfunction. the aim of our study was to identify predictors of mortality in patients treated with ecmo in referral centers and to develop a score in order to better allocate resources and to define the best timing of ecmo institution. the present study is in compliance with the declaration of helsinki. in all patients ecmo was started emergently, and informed consent was waived according to italian legislation. individual data were anonymous according to the health ministry mandate for epidemiological and outcome surveillance of the ecmonet program. the approval of the local ethics committees was therefore waived with no further informed consent required from the patients. the data set from the ecmonet was used to set up a prospective multicenter cohort study. the ecmonet is a national network that includes all severely ill patients with suspected h n virus infection admitted to the intensive care units (icu) of italian tertiary care centers, endorsed and supported by the italian ministry of health [ ] . the ecmonet data set collected the epidemiological and clinical features, treatment data and outcomes of patients with ards suffering from confirmed or suspected h n influenza a who received ecmo according to predefined ecmonet eligibility criteria between august and march [ ] . baseline parameters were collected before ecmo cannulation. all patients with severe ards related to suspected h n influenza a were included if at least one of the inclusion criteria was fulfilled despite the use of available rescue therapies: oxygenation index (oi) [ , pao /fio \ with peep c cmh o (in patients already admitted to one of the ecmonet centers) or pao /fio \ with peep c cmh o (in patients still to be transferred), ph \ . for at least h or hemodynamic instability. exclusion criteria were intracranial bleeding or another major contraindication to anticoagulation, pre-existing severe disability and poor prognosis because of the underlying disease. mechanical ventilation for more than days was considered a relative exclusion criterion [ ] . all adult patients were admitted to the icu of of the italian tertiary care centers. the ecmo circuit setup consisted of a centrifugal pump and a coated polymethylpentene oxygenator. percutaneous cannulation was performed using the seldinger technique: patients received vv ecmo (femoral-jugular in cases, femoral-femoral in , jugular-jugular in ); in patient vv ecmo was initiated and sequentially transitioned to va ecmo triggered by refractory hemodynamic impairment. all patients received intravenous continuous infusion of unfractionated heparin, antiviral therapy with oseltamivir mg twice a day and broad-spectrum antibiotics. continuous variables are reported as mean ± standard deviation or median and interquartile range, whereas categorical variables are reported as absolute numbers and percentages. unadjusted univariate analyses were based on the mann-whitney u or median test and fisher's exact test, respectively, with the computation of % confidence intervals. for building a model predicting intrahospital mortality, multivariable analyses were performed. in detail, we modeled data using generalized estimating equations (gee) to consider correlating features within the center, assuming the same correlation between any two elements of a cluster (exchangeable correlation matrix) [ , ] . as the performance of the multivariate model depends on the initial number of variables [ ] , we included all the variables that were statistically associated with a p value b . in the univariate models. in addition, we compared models within a nested subgroup of selected variables by quasi-likelihood under the independence model criterion (qic) [ ] . we started with factors revealing high significance (p = . ) in the univariate model and proceeded with forward selection. in multivariate regression, statistical significance was set at the two-tailed . level. when gee regression coefficients could not be estimated (i.e., in case the generalized hessian matrix was not positively definite) [ ] , we limited the analysis to the association performed by the fisher exact test or mann-whitney u test for categorical or continuous variables, respectively. based on the coefficients of the multivariate analysis, we combined predictors for the assessment of mortality risk in patients who presented as ecmo candidates into a new score-the ecmonet score. with the aim to be as intuitive as possible, the score was constructed to give a result between and . thus, the number resulting from score calculation can be easily associated with the mortality risk. in addition, each of the five parameters is given weight by the value measured (partial score). the partial score for each parameter was established according to its frequency distribution and its weight in the final gee model. the ecmonet score can be calculated with the following formula where ps i is the partial score assigned to each parameter. the goodness-of-fit of the model, plotting mortality status versus ecmonet score, was confirmed by the gee model and qic statistic. besides, c-statistics (area under roc curve) were calculated as a measure of a model's ability to discriminate between survivors and non-survivors [ ] . from the roc curve analysis, the best cutoff value was identified as the point with the highest value sensitivity and specificity (youden index: se ? sp - ) [ ] . the % confidence interval for accuracy, sensitivity and specificity was calculated with normal approximation. in order to provide further external validation of the accuracy of the ecmonet score, we used an external test set containing patients suffering from ards because of h n who received ecmo treatment in other countries [ , ] or in the italian ecmonet centers during the h n influenza a epidemics. the full data set was available for patients in the validation group. fifty-nine patients received vv ecmo, and one patient received va ecmo. four were converted from vv to va ecmo because of circulatory failure during treatment [ ] . two examples of the ecmonet score calculation on paradigmatic clinical cases are also available as supplementary online material. statistical significance was set at the two-tailed . level for all hypothesis testing. data were analyzed with sas . (sas institute inc., cary, nc, usa). among the patients of the h n pandemic, ( %) had confirmed h n -associated ards with a survival rate of %. the remaining ( %) patients without confirmed h n -associated ards presented a survival rate of %. twenty-eight patients were referred from remote hospitals to the ecmonet referral centers and treated with ecmo. multiple organ failure associated with sepsis was the most common cause of death ( %), followed by septic shock ( %). all nonsurvivors were still on ecmo at the time of death. as shown in table , all baseline characteristics, clinical parameters and vital signs were tested by univariate analysis. using multivariate analysis, we identified five statistically significant predictors of death: bilirubin value (or = . , % ci . - . , p \ . ), systemic mean arterial pressure (or = . , % ci . - . , p \ . ), hematocrit value (or = . , % ci . - . , p = . ), preecmo hospital length of stay (or = . , % ci . - . , p = . ) and creatinine level (or = . , % ci . - . , p = . ). these five parameters were then entered into the ecmonet score (table ). when evaluated in the univariate gee model, the ecmonet score was a statistically significant predictor of mortality (or = . , % ci . - . , p \ . ). the roc analysis further confirmed the high accuracy of the ecmonet score (c = . , % ci . - . , p \ . ) for the prediction of the mortality risk in patients on ecmo. an ecmonet score of . was found to be the most appropriate cutoff for mortality risk prediction. continuous parameters presented as mean ± sd, categorical data as n (%) bmi body max index, bsa body surface area, pbw partial weight bearing, ecmo extracorporeal membrane oxygenation, icu intensive care unit, mv mechanical ventilation, els extracorporeal life support, copd chronic obstructive pulmonary disease, bipap bilevel positive airway pressure, hfov high-frequency oscillatory ventilation, cpappsv continuous positive airway pressure and pressure support ventilation, crrt continuos renal replacement therapy, simv invasive mechanical ventilation synchronized, sofa sequential organ failure assessment, paco partial pressure of carbon dioxide, map mean arterial pressure, pcv pressure control ventilation, peep positive end expiratory pressure, cvp central venous pressure, vt tidal volume revealed a lower performance in the evaluation of preimplant mortality risk compared to the ecmonet score. we further analyzed the performance of the ecmonet score to the subgroups of patients referred or not referred from remote hospitals. not only was the prediction of mortality risk excellent in the patients with h n infection (c = . , % ci . - . , p \ . ), but also the ecmonet score performed well in both groups of patients (n = ), referred (c = . , % ci . - . , p = . ) or not referred (n = ) from remote hospitals (c = . , % ci . - . , p \ . ).furthermore, we examined the reliability of the ecmonet score by an external validation analysis: the validation group consisted of patients with ards ( male and female), of whom % ( / ) had confirmed h n infection, and % ( / ) were transferred from remote hospitals to the tertiary referral centers after the initiation of treatment with extracorporeal support. mean age was ± years; overall survival rate was % ( / ).the roc analysis (fig. ) of this external test set revealed a strong capacity of the ecmonet score to distinguish survivors from nonsurvivors (c = . , % ci . - . , p = . ). the accuracy was % ( % ic - %), and sensitivity and specificity were % ( % ic - %) and % ( % ic - %), respectively. this study shows that mortality of adult patients suffering from influenza a (h n )-related ards undergoing vv ecmo is related to extrapulmonary organ function at the time of cannulation. preecmo hospital length of stay; creatinine, bilirubin and hematocrit values; and systemic mean arterial pressure were significantly associated with mortality as assessed by multivariate analysis, while respiratory parameters were not associated with survival. to improve risk stratification and prediction of mortality risk at the time of vv ecmo initiation, we developed a multifactorial scoring system-the ecmonet score. up to now, most data explaining the rates and causes of death refer to the time point after the start of ecmo: in a large multicenter database of , adult patients supported with ecmo for respiratory failure, survival at hospital discharge was % [ ] . non-survivors displayed a higher rate of complications, including mechanical circuit complications; renal complications; surgical, gi and pulmonary hemorrhages; hyperglycemia, infections, arrhythmias and pneumothorax [ ] . in a population of pediatric patients undergoing va ecmo, morris and colleagues found that the development of renal and hepatic dysfunction during ecmo predicted mortality in postoperative patients with statistical significance [ ] . recently, smalley et al. [ ] performed a retrospective study on children with pneumonia and managed with ecmo. in their study, the need to change the ecmo circuit and the need for continuous renal replacement therapy were predictors of death. wagner et al. [ ] found that, among risk factors analyzed in a total of patients receiving pulmonary ecmo, only preecmo serum creatinine levels correlated with survival. this result is in line with our findings, even if in their study adults, children and neonates suffering from different pulmonary diseases and treated with either vv or va ecmo were all analyzed as a unique study group. however, studies on this topic are few and potentially biased by the multiple etiologies of respiratory failure. in contrast, our patients presented as an homogeneous population with h n -associated pneumonia (confirmed in . %) referred to tertiary ecmo centers. furthermore, patients enrolled in our study were stringently treated with vv ecmo according to a national protocol with definite inclusion and exclusion criteria. accordingly patient management was similar in the tertiary centers, as the ecmonet organized multiple ecmo training courses open to physicians, perfusionists and nurses [ ] . the parameters identified in our study are very simple to implement clinically, and the use of the ecmonet score for the evaluation of critically ill patients for vv ecmo institution can be applied easily to patients referred from remote hospitals. external validation indicates that the information provided by the ecmonet score is statistically robust in further patient groups. the potential benefits of the new score, however, may be not limited to the setting of h n influenza a virusrelated acute lung failure. after further validation in different settings of acute respiratory distress syndrome, endorsing this score in clinical practice would allow cannulation of patients in the presence of organ dysfunction before strict respiratory criteria are met and refusal of ecmo in patients with high predicted mortality. protective ventilation was shown to improve survival in patients with ards by the ards network [ ] . besides its lung-protective effects, the favorable effects of ecmo appear to be related to its beneficial hemodynamic impact on preserving distal perfusion (i.e., kidney, liver), particularly if focusing on causes of death. ecmo is safer, cheaper and simpler than in previous eras [ ] . while the cesar trial showed an improvement in survival [ ] , the ecmonet experience demonstrated that its application is feasible and effective [ ] . moreover, the ecmonet data set analysis allowed the development of the ecmonet score, and the validation analysis revealed a potentially strong impact on clinical practice. some limitations of this study should be acknowledged. first, complications occurring during ecmo have a strong impact on the outcome, and these are not addressed with baseline parameters. our study used predefined indications for ecmo based on gas exchange and ventilator pressure, which are not universally standardized and remain an important matter of discussion. another limitation is the inability to provide a distinction between patients with viral sepsis at baseline and those who had superinfection, as the majority of deaths in our population were related to multiple organ failure associated with sepsis and septic shock. however, the facts should not be underestimated that the overlap between shock, sirs, ecmo itself and sepsis is always part of the clinical scenario in patients undergoing extracorporeal support [ ] and that all patients were already septic at baseline. finally, the accuracy of the ecmonet score [ % ( % ic - %)], and the sensitivity and specificity [ % ( % ic - %) and % ( % ic - %), respectively] should be further validated in larger ards populations. our data provide new perspectives concerning the allocation of resources for vv ecmo. we confirm the strong clinical perception that survival is strongly correlated to extrapulmonary organ function at the time of ecmo initiation. this knowledge may help to identify potential candidates for ecmo support according to their mortality risk and provides guidance to solve crucial economic and ethical issues. pain therapy, federico ii university, naples, italy); f. bruno, s. grasso (anesthesiology and intensive care unity, department of emergency medicine and organ transplants, bari university, bari, italy); l. lorini (department of anesthesiology and intensive care, ospedali riuniti, bergamo, italy); c. ori, s. rossi, p. persona (institute of anesthesiology and intensive care, university hospital of padua, padua, italy). the ecmonet is a national network instituted by the italian ministry of health in response to the h n pandemic. the italian ministry of health allocated all economic, human and technological resources required for the development and activity of the ecmonet. our study used the ecmonet registry as the main data source. we did not receive funds from the italian ministry of health for the present study. the analysis presented in this study was entirely supported by departmental funds. the authors had full control of primary data, and they agree to allow the journal to review their data if requested. cesar: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure the australia new zealand extracorporeal membrane oxygenation (anz ecmo) influenza investigators extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome referral to an extractorporeal membrane oxygenation center and mortality among patients with severe influenza a (h n ) extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database virusassociated hemophagocytic syndrome as a major contributor to death in patients with influenza a (h n ) infection the italian ecmo network experience during the influenza a(h n ) pandemic: preparation for severe respiratory emergency outbreaks regression analysis for correlated data longitudinal data analysis using generalized linear models multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors akaike's information criterion in generalized estimating equations what to do when your hessian is not invertible: alternatives to model respecification in nonlinear estimation roc analysis estimation of the youden index and its associated cutoff point extracorporeal membrane oxygenation for pandemic h n respiratory failure risk factors for mortality in pediatric cardiac intensive care unit patients managed with extracorporeal membrane oxygenation butt w ( ) outcomes in children with refractory pneumonia supported with extracorporeal membrane oxygenation is it possible to predict outcome in pulmonary ecmo? analysis of preoperative risk factors simulation-based training of extracorporeal membrane oxygenation (ecmo) during h n influenza pandemic: the italian experience ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome: the acute respiratory distress syndrome network contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era diagnosis of infection in patients undergoing extracorporeal membrane oxygenation: a case-control study key: cord- -hya ch authors: nan title: abstracts der . jahrestagung der gesellschaft für neonatologie und pädiatrische intensivmedizin date: - - journal: monatsschr kinderheilkd doi: . /s - - -y sha: doc_id: cord_uid: hya ch nan von der körperhöhe der mutter beeinflusst wird. dieses hat dann auch folgen für das ursachenspektrum von schwangerschafts-und geburtsrisiken bei hypotophen, eutrophen und hypertrophen neugeborenen. maternal prepregnancy weight and neonatal outcome: does adiposity really matter? ziel. es werden die bedeutung ausgewählter mütterlicher merkmale (alter, körpergewicht, körperhöhe, bmi, gewichtszunahme während der schwangerschaft, gestationsdiabetes, rauchverhalten, parität, alleinstehend/nicht alleinstehend) für das auftreten einer neonatalen makrosomie bei reifgeborenen analysiert. methode. die daten von . neugeborenen der jahre - aus der deutschen perinatalerhebung von bundesländern werden analysiert. die maternalen daten von kinder > . geburtsgewichtsperzentile (n= . ) wurden mit den von eutrophen termingeborenen (n= . ) verglichen. die statistische auswertung erfolgte deskriptiv sowie mittels χ -test. die risikokalkulation erfolgte mittels univariater und multivariablen logistischer regression mit dem programmpaket "spss" im rechenzentrum der universität rostock. ergebnisse. risikofaktoren für ein hypertrophes neugeborenes sind ( ) ein maternales gewicht > kg (or , % ci , - , ) und mütterliche adipositas (bmi> ). (or , ). ( ) ein schwangerschaftsdiabetes (or , ), ( ) eine überstarke gewichtszunahme > kg während der schwangerschaft (or , ). ( ) mehrgebärende haben häufiger hypertrophe neugeborene (or , ). Überraschender weise stellen das mütterliche alter und alleinstehende mütter keine wesentlichen unabhängigen risikofaktoren dar. schlussfolgerung. es konnten für eine mitteleuropäische population risikofaktoren definiert werden, die für die primär-und sekundärprävention von fetalen makrosomien ansatzpunkte geben können. background. hypoxic-ischemic encephalopathy (hie) still is a major cause of neonatal mortality and morbidity. the amplitude-integrated electroencephalogram (aeeg) is reliable for prediction of outcome in asphyxiated neonates. near-infrared spectroscopy (nirs) offers the possibility to continuously monitor cerebral oxygen saturation. only few data have been published on the combined use of nirs and aeeg in neonates cooled for hie. the aim of this study was to investigate the correlation between continuous aeeg and nirs during the first days of life in hie. methods. aeeg: brain function was measured continuously immediately after the hypoxic event, during hypothermia, until the end of rewarming using a olympic (natus©). aeeg tracings were analysed for background patterns, appearance of sleep-wake cycling and the presence of seizure activity. furthermore, a combined aeeg-score was calculated for the timeperiod before, during and after hypothermia. nirs: patients were monitored using nirs (invos system by covidien©) for the mentioned time period. changes in regional cerebral oxygen saturation (rcso ) were measured. fractional tissue oxygen extraction (ftoe) was calculated for the entire duration of the measurement in order to investigate the balance between oxygen delivery and oxygen supply. results. a significant correlation coefficient (corrc) was found between swz and rcso post cooling (corrc: . ) as well as ftoe during (corrc: . ) and post cooling (corrc: . ). furthermore, a significant corrc was found between the total aeeg score and rcso post cooling (corrc: . ) as well as ftoe during (corrc: . ) and post cooling (corrc: . ). conclusion. our data show a significant correlation between continuous aeeg monitoring, which is a valuable and reliable method for prediction of neurodevelopmental outcome in neonates with hie, and nirs measurements. therefore, we suggest that nirs can serve as an additional prognostic tool in hie. n. baik , b. urlesberger , b. schwaberger , g. schmölzer , l. mileder , a. avian , g. pichler universitätsklinik für kinder-und jugendheilkunde, klinische abteilung für neonatologie, graz, Österreich, department of neonatology, royal alexandra hospital, edmonton, canada, edmonton, kanada, medizinische universität graz, medizinische informatik und statistik, graz, Österreich hintergrund. nichtinvasive Überwachung des gehirns mit nahinfrarot-spektroskopie (nirs) während der adaptationsphase nach der geburt ist von wachsendem interesse. die referenzwerte von crso und cftoe gemessen mit invos c wurden daher bereits etabliert. fragestellung. das ziel dieser prospektiven beobachtungsstudie war es die referenzwerte und perzentilen der regionalen zerebralen oxygenierung (ctoi) und der zerebralen sauerstoffgewebsextraktion (cftoe)gemessen mit niro nx -während der ersten minuten nach der geburt bei früh-und neugeborenen mit unauffälliger adaptationsphase zu definieren. material und methoden. ctoi wurde mit niro nx in den ersten minuten nach der kaiserschnittentbindung in früh-und neugeborenen gemessen. der nirs sensor wurde an der stirn rechts frontal angelegt. periphere arterielle sauerstoffsättigung (spo ) und die herzfrequenz (hf) wurden kontinuierlich mittels pulsoxymetrie gemessen. cftoe wurde aus ctoi und spo berechnet. neugeborene, die während der adaptationsphase sauerstoff-und/oder respiratorische unterstützung erhielten, wurden ausgeschlossen. hintergrund. nahinfrarotspektroskopie (nirs) ermöglicht eine kontinuierliche, nichtinvasive messung der zerebralen konzentrationsänderungen von oxygeniertem (Δo hb) und desoxygeniertem hämoglobin (Δhhb) bei neugeborenen. veränderungen des totalen hämoglobins (Δchb=Δo hb+Δhhb) können unter berücksichtigung der hämoglobinkonzentration in den großen gefäßen in veränderungen des zerebralen blutvolumens (Δcbv) umgerechnet werden. unsere studiengruppe zeigte einen signifikanten abfall des cbv bei gesunden reifgeborenen in den ersten lebensminuten. bislang gibt es jedoch keine daten, wie sich das cbv während der postnatalen adaptationsphase von früh-und reifgeborenen mit und ohne atemunterstützung verhält. fragestellung. wie verändert sich das Δcbv in der adaptationsphase von früh-und reifgeborenen mit und ohne atemunterstützung? material und methode. diese sin gle-center-studie wurde als prospektive beobachtungsstudie durchgeführt. inkludiert wurden früh-und reifgeborene mit und ohne notwendigkeit einer atemunterstützung nach schnittentbindung. für die nirs-messungen wurde ein "niro- -nx" (hamamatsu; japan) verwendet. der nirs-sensor wurde rechts frontal mit elastischer binde fixiert. der verlauf des Δcbv wurde für die unmittelbare postnatale adaptationsphase über minuten berechnet. ergebnisse. es wurden insgesamt neugeborene inkludiert, davon waren frühgeborene ( mit und ohne atemunterstützung) mit einem mittleren gestationsalter von ± wochen und reifgeborene ( mit und ohne atemunterstützung) mit einem mittleren gestationsalter von ± wochen. Δcbv bei früh-und reifgeborenen zeigte sich ein signifikanter abfall des cbv in den ersten lebensminuten. bei frühgeborenen ohne atemunterstützung ist das cbv um , (± , ) ml/ g gehirngewebe, bei frühgeborenen mit atemunterstützung um , (± , ) ml/ g gehirngewebe abgefallen. bei reifgeborenen ohne atemunterstützung ist das cbv um , (± , ) ml/ g gehirngewebe, bei reifgeborenen mit atemunterstützung um , (± , ) ml/ g gehirngewebe abgefallen. schlussfolgerung. bei früh-und reifgeborenen findet man unmittelbar postnatal einen abfall des cbv, wobei dieser bei gesunden reifgeborenen ohne atemunterstützung am stärksten ausgeprägt ist. inwieweit diese beobachtung vor allem bei frühgeborenen mit risiko einer zerebralen schädigung von klinischer relevanz ist, muss in zukünftigen studien geklärt werden. introduction. the amplitude-integrated eeg (aeeg) is becoming more important to monitor brain activity in premature infants. studies have shown that early aeegs correlate with later neurodevelopmental outcome. various scoring systems for the assessment of aeegs are being used, which complicates the comparison of published data. the aim of our study was to compare two scoring systems for aeeg and correlate with the neurodevelopmental outcome. methods. preterm infants [gestational age (ga) < weeks of gestation] who had an aeeg within the first days of life and a neurodevelopmental outcome at the age of were retrospectively included into the study. the aeegs had been analyzed with the aeeg sum score [background activity (ba) = percentage of different background patterns based on gestational age related standard values, the occurrence of sleep-wake cycles (swc) and seizure activity] and the burdjalov score [continuity (co), cyclicity (cy), amplitude of lower border (lb) and bandwidth span and amplitude of lower border (b) of the aeegs -regardless of gestational age] and the results had been correlated with the outcome [bayley scales (mdi and pdi) at the age of ]. results. both total scores (p≤ . ) and the different subscores correlated statistically significant (p≤ . ) with each other. both total scores showed significant correlation (burdjalov score p= , and aeeg sum score p≤ . ) with the outcome. the burdjalov score showed increasing values with increasing ga, while the aeeg sum score showed no differences in the various ga. conclusion. both scoring systems allow a simple classification of aeegs. the burdjalov score shows specific differences for the ga, while the aeeg sum score correlates better with the later outcome. universitätsklinik für kinder-und jugendheilkunde, klinische abteilung für neonatologie, graz, Österreich, department of neonatology, royal alexandra hospital, edmonton, canada, edmonton, kanada, medizinische universität graz, medizinische informatik und statistik, graz, Österreich fragestellung. ziel dieser studie war es, einen möglichen zusammenhang zwischen regionaler zerebraler oxygenierung (crso ) und mittlerem arteriellen druck (mad) bei früh-und reifgeborenen während der adaptationsphase zu untersuchen. material und methode. in diese prospektive beobachtungsstudie wurden früh-und reifgeborene eingeschlossen. die zerebrale regionale oxygenierung (crso ) wurde mittels nahinfrarot-spektroskopie (nirs) mit dem invos c während der neonatalen adaptationsphase ( minuten unmittelbar nach der geburt) gemessen. der nirs sensor wurde an der stirn links frontal angelegt. ferner wurde ein pulsoxymeter angelegt, um die arterielle sauerstoffsättigung (spo ) und die herzfrequenz (hf) zu überwachen. in der . lebensminute wurde einmalig der blutdruck am linken oberarm gemessen. die zerebrale sauerstoffgewebsextraktion (cftoe) wurde aus spo und crso berechnet. um den zusammenhang zwischen cftoe und mad zu untersuchen, wurde eine korrelationsanalyse durchgeführt. ergebnisse. es wurden insgesamt früh-(n= ) und reifgeborene (n= ) eingeschlossen. das mittlere gestationsalter betrug , ± , wochen bei frühgeborenen, , ± , wochen bei reifgeborenen, das mittlere geburtsgewicht ± g bei frühgeborenen, ± g bei reifgeborenen. die korrelationsanalyse zeigte keinen statistisch signifikanten zusammenhang zwischen mad und cftoe bei reifgeborenen, im gegensatz dazu gab es aber eine statistisch signifikante negative korrelation bei frühgeborenen zwischen mad und cftoe (p= , ). diskussion. die vorliegende beobachtungsstudie zeigt einen statistisch signifikanten zusammenhang zwischen cftoe und mad bei frühgeborenen, obwohl es keinen zusammenhang bei reifgeborenen gibt. dies könnte darauf hindeuten, dass bei reifgeborenen eine funktionierende gefäßautoregulation bereits während der adaptationsphase existiert, während diese bei frühgeborenen fehlt. schlussfolgerung. mad hat einen einfluss auf zerebrale oxygenierung bei frühgeborenen. die Überwachung des mads bereits während der erstversorgung der frühgeborenen könnte für den klinischen alltag relevant sein, um mit der eventuellen therapie die zerebrale oxygenierung positiv zu beeinflussen. peri-/intraventrikuläre blutung bei frühgeborenen: einfluss der zerebralen oxygenierung während der adaptationsphase tationsphase ( minuten unmittelbar nach der geburt) gemessen. der sensor wurde an der stirn links frontal angelegt. ferner wurde präduktal ein pulsoxymeter angelegt, um die arterielle sauerstoffsättigung (spo ) und die herzfrequenz (hf) zu überwachen. ultraschalluntersuchungen des gehirns wurden am tag , , nach der geburt und vor der entlassung durchgeführt, um peri-/intraventrikuläre blutung zu identifizieren. je nach ultraschalluntersuchungsergebnissen wurden die fg in zwei gruppen eingeteilt: ivh-gruppe und non-ivh-gruppe. um die zwei gruppen vergleichbar zu machen, wurden fg mit ivh zu den fg ohne ivh im bezug auf gestationsalter (± woche) und geburtsgewicht (± g) gepaart. ergebnisse. fg wurden in die studie eingeschlossen: der fg entwickelten ivh. diese wurden mit fg ohne ivh aus der non-ivh-gruppe (n= ) verglichen. es gab keinen unterschied zwischen den zwei gruppen in bezug auf spo und hf. die ivh gruppe zeigte statistisch signifikant niedrigere crso -werte als die non-ivh-gruppe ab der minute bis zum ende der beobachtungsphase. schlussfolgerung. die frühgeborenen der ivh-gruppe zeigten signifikant niedrigere crso -werte während der adaptationsphase, obwohl es keinen unterschied in spo und hf gab. das zusätzliche monitoring der zerebralen regionalen oxygenierung mittels nahinfrarot-spektroskopie während der adaptationsphase könnte hilfreich sein, um die frühgeborenen mit einem höheren risiko für spätere ivh-entwicklung bereits während der adaptationsphase zu erkennen. s. herber-jonat hintergrund. ein schweres neonatales lungenversagen führt zum einsatz von additiven therapien, wie der applikation von surfactant, inhalativem stickstoffmonoxid (ino), hochfrequenz-oszillationsbeatmung (hfov) oder der extrakorporalen membranoxygenierung (ecmo). ziel dieser studie war es anwendung und effektivität dieser additiven therapien zu dokumentieren. patienten und methodik. einschlusskriterien waren gestationsalter > ssw, akutes lungenversagen unter invasiver beatmung mit fio > , und anwendung mindestens einer additiven therapie. Über die erhebungseinheit für seltene pädiatrische erkrankungen in deutschland (esped) wurden n= patienten innerhalb von jahren in die studie aufgenommen. die effektivität der jeweiligen additiven therapie wurde durch den behandelnden arzt beurteilt. vorgabe für einen positiven effekt war eine senkung des oxygenierungsindex um oder anstieg der pao /fio ratio um mmhg. ergebnisse. die häufigste diagnose war der surfactantmangel mit , %, gefolgt von pneumonie/sepsis ( , %), mekoniumsaspirationssyndrom und der kongenitalen zwerchfellhernie. surfactant wurde in , % appliziert mit einer effektivität von , %. , % aller patienten wurden mit ino behandelt, mit einer wirksamkeit von , %. hfov wurde bei , % aller fälle mit einer wirksamkeit von , % angewendet. die ec-mo-therapie kam bei , % der patienten zum einsatz und war in , % erfolgreich. die gesamtsterblichkeit innerhalb der kohorte lag bei , %. signifikante einflussfaktoren auf das Überleben waren: die zugrundeliegende diagnose, die anzahl additiver therapien und der initiale effekt additiver therapien ohne ecmo. patienten starben ohne ecmo-therapie. davon lag in fällen eine ecmo kontraindikation vor. die restlichen patienten, die womöglich von einer ecmo-therapie profitiert hätten wurden nicht in ein ecmo-zentrum überwiesen. schlussfolgerung. die anwendung und effektivität additiver therapien beim lungenversagen des neugeborenen entspricht in deutschland den international vorliegenden daten. jedoch zeigt sich, dass jährlich eine bedeutende anzahl neugeborener mit ecmo-indikation nicht an ein entsprechendes zentrum verlegt wird. hintergrund. beim lungenversagen des neugeborenen haben schonende beatmung und die additiven therapien surfactant und stickstoffmonoxid den bedarf für die extrakorporale membranoxygenierung (ecmo) reduziert. die erworbenen atemstörungen mekoniumaspiration und pneumonie/sepsis sind dadurch beherrschbarer geworden, womit die angeborenen atemstörungen mehr ins visier für die ecmo treten. die folgende analyse soll die frage beantworten wie das diagnoseprofil für ein ecmo zentrum heutzutage aussieht und ob sich dadurch die Überlebenszahlen geändert haben. patienten und methodik. in den jahren - wurden an unserem zentrum neugeborene mit der ecmo behandelt. diese patienten wurden hinsichtlich der ursächlichen diagnose und des Überlebens ausgewertet. für die angeborene zwerchfellhernie wurde konsequent ein standardisierter therapiealgorithmus angewendet. ergebnisse. von ecmo patienten ( , %) haben überlebt und konnten nach hause entlassen werden. damit hat sich die gesamtüberlebensrate im vergleich zu früheren daten und den daten der extracorporeal life support organisation (elso) leicht verbessert. und das obwohl die angeborene zwerchfellhernie (cdh) mit fällen noch deutlicher zur führenden diagnose geworden ist. die Überlebensrate der cdh liegt mit , % sogar minimal über dem durchschnitt und deutlich über den ergebnissen der elso. es zeigt sich die besonderheit unseres zentrums mit der spezialisierung auf die diagnose cdh mit durchschnittlich ecmo fällen bei dieser diagnose pro jahr, wobei ca. ein drittel der prä-und postnatal verlegten cdh-kinder mit ecmo behandelt werden. aus allen anderen diagnosegruppen ergaben sich zusammen durchschnittlich ecmo fälle pro jahr. hierbei erfüllten zwei drittel der seit abgeholten neugeborenen die ecmo-kriterien und ein drittel konnte mittels optimierung der therapie stabilisiert werden konnten. die mekoniumaspiration (mas) ist mit , % der ecmo fälle die zweithäufigste diagnose nach der cdh und hierbei überlebten % der patienten. deutlich schlechtere Überlebensraten zeigten die diagnosen primäre persistierende pulmonale hypertension (pphn) [ , % der patienten] mit nur % und die pneumonie/ sepsis [ , %] mit , %. von kindern mit sonstigen diagnosen überlebten . gerade bei der pphn fällt der mit durchschnittlich lebenstagen relativ späte verlegungszeitpunkt auf. schlussfolgerung. ein optimierter therapiealgorithmus und die hohe spezialisierung mit hohen fallzahlen haben bei der diagnose cdh zu deutlich verbesserten ecmo-Überlebensraten geführt. bei allen anderen diagnosen sind die fallzahlen für ecmo rückläufig und es zeigt sich, dass die therapieabläufe für die pphn verbessert werden sollten. täglich wird ab dem zweiten lebenstag bis zum zehnten lebenstag der pda-score erhoben, wobei definierte klinische parameter beurteilt werden: herzgeräusch, sichtbare präkordiale pulsationen, herzfrequenz > /min (ohne hypovolämie), apnoen oder respiratortherapie, kräftige periphere pulse, hepatomegalie, metabolische azidose, respiratorische verschlechterung. es wird pro positivem merkmal ein punkt im score-system vergeben. bei erreichen eines ductus-scores von ≥ punkten wird eine echokardiographische untersuchung (als goldstandard in der diagnostik des pda) initiiert. ergebnisse. das mittlere gestationsalter der studiengruppe beträgt , ssw (σ , ssw). das mittlere geburtsgewicht liegt bei , g (σ , g). die gruppe setzt sich zusammen aus , % männlichen sowie , % weiblichen neonaten. um die einzelnen parameter des vereinfachten pda-scores zu wichten, wurden mittels kreuztabellen die klinischen bestandteile des scores jeweils einzeln der entwicklung eines echokardiogaphisch bestätigten hrpda gegenübergestellt. durch die ermittlung des angepassten residuums, sowie der exakten signifikanz mittels fisher-test konnten die signifikanten, statistisch stärksten einzelparameter ermittelt werden. ein versuch der zusammenfassung der klinischen merkmale mittels logistischer regressionsanalyse konnte einzelne kernmerkmale, wie metabolische azidose, präkordiale pulsationen, periphere pulse sowie apnoe bzw. respiratortherapie (pulmonale verschlechterung) herauskristallisieren. am dritten und vierten lebenstag korrelieren diese parameter am besten mit der entwicklung eines echokardiographisch bestätigten hrpda. schlussfolgerung. der von uns getestete klinische pda-score ist in der anwendung einfach, nichtinvasiv und schnell durchführbar. in kombination mit der kontinuierlichen erfassung dieses klinischen pda-scores lässt sich die echokardiographie gezielter einsetzen und gegebenenfalls die anzahl der notwendigen echokardiografischen untersuchungen reduzieren. hintergrund. der verschluss des ductus arteriosus bei reifen neugeborenen ist mit der bildung eines stabilen thrombus assoziiert. bei frühgeborenen unter g geburtsgewicht verschließt sich ein offener duktus arteriosus (pda) häufig nicht spontan, so dass bei hämodynamischer relevanz ein medikamentöser oder operativer verschluss notwendig werden kann. es ist bisher unklar, ob die postnatale transfusion von adulten thrombozyten den spontanen oder medikamentös induzierten verschluss des pda beeinflusst. fragestellung. in einer retrospektiven datenbankanalyse wurde untersucht, ob die transfusion adulter spender-thrombozyten innerhalb der ersten lebenstage den verschluss eines hämodynamisch relevanten persistierenden duktus arteriosus (hrpda) bei frühgeborenen mit extrem geringem geburtsgewicht und bereits begonnener indomethacin-therapie begünstigt. material und methoden. frühgeborene mit einem geburtsgewicht unter g und einem gestationsalter von bis zu wochen, die zwischen und geboren wurden, wurden retrospektiv untersucht (n= ; ausgangspopulation). für / ( %) lagen alle erforderlichen daten für eine analyse vor. wir definierten eine thrombozytenzahl unter g/l als thrombozytopenie. die dateneingabe sowie die statistische auswertung wurden mittels excel (microsoft corp., usa) und spss (ibm inc., usa) durchgeführt. ergebnisse. von den kindern entwickelten ( , %) einen hrpda und erhielten eine therapie mit indomethacin. zehn dieser kinder verstarben postnatal ( , %) . es bestand kein zusammenhang zwischen der schwere der thrombozytopenie und dem auftreten eines hrpda. der erfolgreiche medikamentöse verschluss eines hrpda war unabhängig von einer postnatal beobachteten thrombozytopenie ( . % vs. . %, mit/ohne thrombozytopenie, p= , ). die transfusion von adulten thrombozyten hatte keinen einfluss auf die notwendigkeit einer duktusligatur ( , % mit vs. , % ohne transfusionen, p= , ). eine analyse nur der überlebenden kinder erbrachte ein ähnliches ergebnis ( , % mit vs. , % ohne transfusionen; p= , ). wesentlicher prädiktiver faktor für das versagen einer medikamentösen duktus-therapie war das postmenstruelle alter bei geburt (p< , ). diskussion. unsere daten zeigen, dass eine postnatale transfusion von adulten thrombozyten keinen effekt auf den erfolg oder misserfolg einer indomethacin-therapie bei hrpda hat. unsere daten widerlegen außerdem frühere beobachtungen, die einen zusammenhang einer thrombozytopenie mit dem auftreten eines hrpda implizierten. eine limitation dieser retrospektiven analyse ist, dass ein signifikanter unterschied zwischen thrombozytopenen und nicht-thrombozytopenen kindern hinsichtlich wesentlicher klinischer parameter (gestationsalter, geburtsgewicht, hirnblutungsrate und mortalität) bestand, so dass anhand der vorgelegten daten keine abschließenden schlüsse gezogen werden können. background. our "artificial placenta" neonatal lung assist device is a stacked array of microfluidic polydimethylsiloxane (pdms) sous (abb. p . . ; schematic of a sou). blood contacting surfaces within the sous need to be hemocompatible, a method using pda as a 'bioglue' to attach a covalent ath complex, a potent anticoagulant, has been developed to achieve hemocompatibility. objective. to quantify ath binding and bioactivity on pda modified sous. methods. quantification and evaluation of surface bound ath was carried out through blood exposure. two sets of oxygenators (n= total) were incubated in dopamine hydrochloride ( mg/ml in pbs, ph . , hrs) which oxidizes to pda. subsequent ath incubation formed the pdms-pda-ath complex ( . mg/ml in pbs, ph . , hrs). i-labeled ath was used as a tracer. one set of sous (n= ) was then exposed whole blood (hematocrit . ) for days. the heparin component of ath, if active, selectively binds antithrombin (at); therefore, the anticoagulant activity of ath modified sous was evaluated by measuring at uptake from plasma ( hrs, n= ) to pdms-pda-ath. i-labeled at was added to plasma as a tracer. results. initially, . µg/cm of ath was bound to the pdms-pda oxygenators after hours. this level suggests monolayers were formed. subsequent exposure to blood removed % after hours, with . µg/ cm of ath remaining on the surface. this indicates the binding of ath to pdms-pda was relatively stable. abb. p - . shows that pdms-pda-ath sous bound . ng/cm of at from plasma, significantly higher than the precursor pdms-pda, at . ng/cm . this demonstrates that the anticoagulant activity of heparin in ath remains active when attached through pda. conclusions. pda, used as an adhesive agent to attach ath to pdms microfluidic sous, provides high ath surface density, increased stability, and increased anticoagulant activity. introduction. in neonatal intensive care units, respiratory insufficiency among low-birth weight infants has been a major cause of mortality. for preterm infants, central umbilical cannulation has been widely performed for administering antibiotics, electrolytes, and nutrients. these umbilical vessels can become a source of vascular access to connect the preterm infant to an artificial placenta (ap) that provides sufficient gas exchange to overcome respiratory distress. the concept of an ap requires large bore access via umbilical vessels. in utero, umbilical artery (ua) and vein (uv) have wide diameters ( - and - mm, respectively). after birth, these vessels constrict, and need to be re-expanded to maintain high extracor- background. respiratory adaptation comprises the fundamental transition from a hydrospheric to an atmospheric environment at birth, realized by different, highly regulated physiologic changes in the cardiorespiratory system. if these are disturbed or delayed, cardiorespiratory disorders occur, frequently appearing as respiratory distress in the first hours of life. the management of respiratory transitional disorders is focused mainly on respiratory support. in addition to conventional therapies, anthroposophically extended medicine offers the possibility of treatment options based on an integrative approach to man and nature, to illness and healing. the anthroposophic medication pulmo/vivianit comp. proved to be effective in the treatment of pulmonary disorders in children and adults without indication of safety problems. therefore, we hypothesized a possible effect in neonatal respiratory transitional disorder. case report . a newborn girl presented progressive signs of respiratory distress after birth. pregnancy, delivery by elective cesarean section at a gestational age of / weeks and primary adaptation had been normal. after repetitive application of pulmo/vivianit comp. orally signs of respiratory distress disappeared within minutes and the girl could stay with the mother under continuous monitoring, that did not reveal abnormal findings until discharge on day five. case report . twin boys were delivered by cesarean section at / weeks of gestation. only the second twin developed signs of respiratory distress including the need for supplemental oxygen. to support the child's own effort in managing the respiratory transition, pulmo/ vivianit comp. was given orally. within minutes this was followed by a gradual improvement of respiratory symptoms. the sustainable effect was confirmed by normal findings during monitoring and regular examinations until discharge on day seven. discussion. respiratory transitional disorders have a high incidence and there is an urgent need for preventive and therapeutic interventions. based on the anthroposophic knowledge of human, nature and substance, the treatment with pulmo/vivianit comp. supports specifically the transitional changes in the respiratory system at birth. the rapid and sustainable improvement of respiratory symptoms and the overall functional state of the babies in both cases following the application of pulmo/vivianit comp. gives reason to be attributed to this specific treatment. no adverse effects could be observed. the idea of specifically supporting the infants own regulative forces in managing the disorder is confirmed by the fact, that the observable development after application of the medication resembles exactly the natural course of the disease, however in an accelerated mode. conclusion. according to the encouraging results presented here, the treatment of respiratory tranistional disorders with pulmo/vivianit comp. merits further attention in clinical practice and research. introduction. necrotizing enterocolitis, an idiopathic inflammatory bowel necrosis, is a common gastrointestinal emergency in very low birth weight premature neonates. neonatal intestinal macrophages progressively acquire a gestational age-dependent non-inflammatory profile. thus, the higher proinflammatory activity of premature intestinal macrophages might contribute to inflammatory mucosal injury leading to nec. lactoferrin, a mammalian milk glycoprotein, has various effects on the host innate immune defense and showed promising results in clinical studies to prevent late-onset sepsis and nec in premature infants. therefore, the aim of the study was to investigate the effect of human lactoferrin on lps and lta stimulated cord blood monocyte-derived macrophages of term and preterm neonates compared to healthy adults. methods. cord blood and peripheral blood monocytes were differentiated in the presence or absence of lactoferrin and then stimulated with the tlr agonist lta or the tlr agonist lps. the surface expression of tlr /tlr , tlr-signaling, intracellular tnfα production and secretion were evaluated by flow cytometry. results. lactoferrin attenuates in a dose-dependent manner the tnfα production of monocyte-derived macrophages among the age groups. this effect is mediated by a decreased tlr-expression of lactoferrin treated macrophages and resulted in diminished tlr-signaling of p and erk / upon stimulation with lps and lta. conclusion. in summary, human lactoferrin attenuates the proinflammatory response upon tlr /tlr activation of neonatal macrophages. these data show that lactoferrin mediates anti-inflammatory effects by down-regulation of tlr and tlr expression on neonatal macrophages. we thus conclude that these anti-inflammatory properties might be a potential mechanism contributing to the preventive effects of lactoferrin in the premature gut. background. very early life pain exposure and stress induces alterations in the developing brain and leads to altered pain sensitivity. in premature infants with a history of numerous early postnatal adverse events, behavioral responsiveness and hypothalamic-pituitary-adrenal (hpa) axis reactivity may show alterations as well. aims. we compared a multidimensional response to a painful situation (vaccination) in three month old infants. the study involved very preterm, moderate to late preterm infants and full-term infants with varying exposure to pain and stress within the first weeks of life. study design. at the age of three months, we evaluated the infants' reactivity to intramuscular injections for immunization. subjects. the study included very preterm infants, moderate to late preterm infants and full-term infants. outcome measures. we assessed heart rate recovery, bernese pain score and increase of salivary cortisol following vaccination. we also evaluated the flexor withdrawal reflex threshold as well as prechtl's general movements. secondly, we assessed factors potentially influencing pain reactivity such as exposure to pain/stress, gender, use of steroids or opioids and mechanical ventilation. results. very preterm, moderate to late preterm and full-term infants showed different reactivity to pain in all analyzed aspects. very preterm infants showed a lower level of behavioral and physiologic reactivity and exposure to pain/stress predicted lower cortisol increase. conclusion. at three months of age, very preterm infants show an altered level of hpa axis reactivity. efforts aiming at minimizing pain and stress in premature infants should be taken. background. moderately and late preterm infants represent a considerable and increasing proportion of infants cared for in neonatal departments worldwide. preterm infants parents are at risk for postpartal depression (ppd) and traumatization (ptsd) and preterm infants are at risk for developmental impairment. aim. to assess the correlation of parental ppd and ptsd and infants' neurologic abnormalities and illness severity. subjects. we studied mothers and fathers of preterm infants (born at to weeks of gestation) and mothers and fathers of fullterm infants. we assessed parental ppd, ptsd and perceived social support and infants' neurologic development at birth, term and three months corrected age. results. preterm mothers and fathers had significant higher depression scores after birth compared to fullterm parents (p= . and . ). preterm fathers also had higher traumatization scores compared to fullterm fathers (p< . ). probable or possible ppd/ptsd was not correlated to infant's illness severity. no differences in neurologic development were found between preterm and fullterm infants. conclusion. moderate to late preterm infants' parents are at increased risk for ppd irrespective of infants' neurologic development or illness severity. aim. this study evaluated the impact of blood sampling via peripheral arterial catheters on cerebral oxygenation and blood volume as a function of blood sampling velocity. methods. near infrared spectroscopy was applied to very low birth weight infants during peripheral arterial blood sampling. changes in cerebral oxygenated, deoxygenated and total haemoglobin, cerebral blood volume and cerebral oxygenation index were recorded. heart rate and oxygen saturation were measured continuously. to assess the impact of blood sampling velocity, both fast second and slow second sampling procedures were performed in a cross-over study design, in which the order of sampling velocities was randomised for each patient. results. both fast and slow blood sampling procedures resulted in a significant decrease in cerebral oxygenation index (fast, p= . , slow, p= . ), and an increase in mean heart rate (both p= . ) and mean blood pressure (p= . and . ). oxygenated and total haemoglobin and cerebral blood volume only decreased significantly after slow blood sampling (p< . ). conclusion. blood sampling from peripheral arterial catheters leads to significant fluctuations in cerebral oxygenation independent of the sampling velocity. changes are comparable to those reported from umbilical blood sampling. we advise that blood sampling should be restricted as much as possible. l vapotherm l vapotherm l optiflow l optiflow background. there are different organisational models to manage a nicu. we recently introduced "microsystems" and cohorting of patients according to acuity in our level iii unit. one outcome parameter to assess the impact of this change is the noise level as this implementation will create designated areas with more and less intensive care within the nicu. we hypothesize that noise levels will be different in both areas before and after introduction. weekends: compared to weekdays, average noise levels were significantly reduced by at least dba to ± . dba (day) and ± . dba (night). conclusion. measured noise levels are higher than current recommendations for nicus (aap: < dba). noise level seems to be more affected by organisational conditions (e.g. handover, day/night and weekends). overall, ms seems to lower the noise exposition significantly; it does not increase the noise exposition in the acute area but reduces it in the intermediate area. acknowledgement. the project is funded by hahso. background. there are different organisational models to manage a nicu. we recently introduced "microsystems" and cohorting of patients according to acuity in our level iii unit. one outcome parameter to assess the impact of this introduction is the length of rounds. this implementation will create designated areas with more and less intensive care within the nicu. we hypothesize that round length will be shorter after introduction of the new model. introduction. evidence is inconsistent to support checking gastric residual volumes (grv) in predicting feeding intolerance in preterm infants. checking of gastric residual volume remains standard practice in guiding feeding advancement in several neonatal centers. we hypothesizes that this practice delays establishment of full enteral feeding with associated complications. objective. the effect on time to reach full feeds ( ml/k/day) of not checking gastric residual volume in advancing feeds in preterm infants. results. infants were enrolled. there was no difference in time to reach full feeds in both groups. there was no difference in episodes of feeding interruptions, incidence of sepsis, reaching bw, and % of bw between two groups. however, two infants in the control group developed nec. please see table and for results. conclusion. there were no adverse events noted. the time to achieve full enteral feeds was short in both groups. in clinical practice, vlbw babies take longer time to reach full enteral feeds and gastric residuals could be a significant barrier to advancement of feeds. this study serves as a feasibility trial to do multicenter rct to study effect of not checking gastric residual on time to reach full feeds and incidence of nec in vlbw babies. application of fortifier during breastfeeding -a new perspective for the discharged premature infant? background. to meet the nutritional needs of preterm infants and to establish adequate growth, multicomponent fortifiers are added to expressed human milk until term or in growth restriction up to weeks of gestation according to the espghan guidelines. this is in conflict with direct breastfeeding. we established a method of feeding fortifier with finger feeder during breastfeeding and investigated the impact of this new method on weight gain in preterm born infants after discharge. furthermore, acceptance and practicability of fortification with the finger feeder were evaluated. materials und methods. infants born < weeks were included in this observational study. before discharge mothers were trained by lactation consultants to feed fortifier with finger-feeder during breastfeeding. therefore the fortifier was dissolved in ml of warm water. the mixture was drawn up in a syringe attached to a finger-feeder and injected slowly in the mouth corner of the infant during breastfeeding. primary outcome of the study was weight gain; secondary outcomes were acceptance and practicability of this new method. results. in total, infants were analysed and divided into "fortifier acceptors" (n= ) and "non-fortifier acceptors" (n= ). demographic parameters were similar between the two groups. weight gain per day after discharge was higher in the fortifier acceptors (median weight gain: , g/d vs. , g/d, p= , ) without reaching statistical significance. in % of the study population, the acceptance was very high; the other half reported feeding problems and irritation of the infant due to fingerfeeder use. discussion. finger-feeder use for fortifier application in preterm infants enables mothers to exclusively breastfeed their baby. weight gain of premature infants after discharge was higher in the group where mothers used this new method. a after passage through the ngt (a total of runs and measurements using a new ngt for each individual run), concentrations of retinol palmitate were measured. the same measurements were performed with droplets of vitamin a mixed in ml of the same preterm formula feeds over a -minute period. these measurements were then compared to and droplets of vitamin a in ml and ml of preterm formula feeds without prior passage through a ngt ( runs each). all measurements were performed in preterm formula after a run through the ngt and not in a blood sample. retinyl palmitate was extracted from formula and oil samples ( µl each) by adding tetrahydrofuran (thf; , ml), vortexing and centrifugation. hplc buffer ( % acetonitril; % thf; mg butylhydroxytoluol as antioxidant) was added to supernatant of milk samples ( , ml) and oil samples ( µl). analysis was performed using standard hplc method using uv-detection at nm. results. the measurements were as follows: droplets of vitamin a in ml of feeds: ± µm; droplets of vitamin a in ml of feeds: ± µm; droplets of vitamin a in ml of preterm formula without prior passage through ngt: ± µm, and droplets of vitamin a in ml of preterm feeds ± µm. no significant differences were seen between the measurements (p> . ). conclusions. we conclude that vitamin a can be given as an oral solution with preterm formula feeds through a ngt, yielding similar concentrations when compared to oral administration. this finding may be of relevance to the conceptualization of future studies in the field of neonatology and pediatrics using vitamin a preparations. background and aim. studies show that more than two thirds of perinatal death could be attributed to insufficient or ineffective team communication [ ] . therefore, it has been suggested to include simulationbased learning methods to acquire and enhance important skills for high-risk events such as neonatal resuscitation [ ] . high fidelity simulation training is an ideal tool to improve team behavior [ ] . we aim to examine if targeted simulation training improves skills, the postnatal management of extremely preterm infants, teamwork and communication during simulated neonatal scenarios. methods. physicians and nurses from several international hospitals are invited to our simulation centre. during a two-day workshop(ws), participants are exposed to different simulation scenarios. the ws includes delivery room management as well as less invasive surfactant administration. after a theoretical session, the participants are actively involved in simulation scenarios using the premiehal®/newbornhal®. all simulations are video recorded using simstation. the simulation room is fully equipped and resembles a neonatal intensive care unit (nicu). after each simulation, participants receive feedback using structured debriefing and video analysis. all participants have to complete a preand post-ws questionnaire. follow-up-questionnaires after three and months post-ws are sent by e-mail. these questionnaires are used to evaluate the clinical benefit of the training. the pre-ws questionnaire includes demographic data of participants (e.g. home institutional guidelines), current teamwork and communication during emergency situations in their nicu. post-ws questionnaires assess their experience with the ws and their own learning effect. the follow-up questionnaires aim to determine whether the ws impacts the participants' approach of neonatal emergencies, teamwork, and communication or improves patient safety at the participants home nicu. results. this is an ongoing study. by comparing pre-, post-and followup questionnaires we can identify if the participants changed the management in their home hospitals and if these changes are related to a better outcome. furthermore, we can identify what problems and obstacles occur during this process of change. the first analysis showed that our ws led to the introduction of regular simulation team trainings at the participant's hospital, to a change of teamwork and communication (e.g. identification of the team-leader) and to a better cooperation with the department of obstetrics and gynaecology. also, participants wish to introduce special skills(e.g. developmental care handling procedures, less invasive surfactant administration procedure)in their nicus. discussion. we employed a new approach of ongoing education and skills enhancement during the immediately newborn care. global rating scales should be used for the objective measurement of teamwork before and after the ws. on-site visits after the ws for evaluating the benefit of the changes and to help introducing new methods locally would be preferable. intuitive parenting: a dialectic counterpart to the infant's integrative competence diagnostic interview to assess regulatory disorders in infancy and toddlerhood (baby-dips) eltern-belastungs-inventar. deutsche version des parenting stress index (psi) the utility of simulation in medical education: what is the evidence? team training in the neonatal resuscitation program for interns: teamwork and quality of resuscitations münster schlaganfallregister unterscheiden sich anzahl der intubationsversuche und gesamtdauer der intubation zwischen zwei perinatalzentren (pnz) mit unterschiedlichen prämedikationsrichtlinien? material und methoden. an zwei level -pnz (pnz und pnz ) wurden prospektiv in einem zeitraum von monaten früh-und reifgeborene untersucht, die endotracheal intubiert wurden. anhand einer videodokumentation wurden anzahl der intubationsversuche und gesamtdauer vom erstmaligen einführen des tubus in die nase bis erreichen der lage der fixierung evaluiert. ein intubationsversuch begann und endete jeweils mittelwert (quartilen) und an pnz , ( ; ) (p= , ). die gesamtdauer der intubation mit prämedikation war an anzahl der intubationsversuche (nicht signifikant) und gesamtdauer (signifikant) der intubation waren bei pnz geringer als bei pnz . ohne prämedikation (nur an pnz durchgeführt) dauerten elektive intubationen kürzer als mit. dies spiegelt vermutlich die anweisung in pnz wider, dass prämedikation nur bei abwehr/ schmerzreaktion des kindes gegeben werden sollte, so dass wartezeiten zur applikation entstanden. schlussfolgerung. an pnz erhielten % der kinder zwei, % drei und % vier medikamente, an pnz erhielten % kein medikament, % eines acknowledgements. we wish to acknowledge the contribution of medical and nursing staff at neonatal intensive care unit at mcmaster children hospital to conduct the study. abstracts scheint demnach eine größere bedeutung für das belastungserleben zu haben, als das kindliche regulationsverhalten. schlussfolgerung. für das langfristige gelingen der co-regulation zwischen eltern und kind spielt das elterliche selbstvertrauen eine wesentliche rolle (papoušek u. papoušek, ) . so ergibt sich für die nachsorge der frühgeborenen und ihrer familien der anspruch, neben entwicklungsthemen des kindes, auch die psychische anpassung der eltern und insbesondere deren elterliche kompetenzwahrnehmung in den blick zu nehmen. methoden. alle studierenden des reformstudiengangs medizin des . semesters wurden befragt, um freiwillig an der studie teilzunehmen. studierende wurden eingeschlossen und in zwei gruppen randomisiert: simmed-gruppe (n= ) und campus-gruppe (n= ). den gruppen wurde eine typische anamnese eines kleinkindes mit meningokokken-sepsis präsentiert und die studierenden hatten minuten zeit, den virtuellen patienten (simmed bzw. campus) zu untersuchen, diagnostische maßnahmen durchzuführen und entsprechend zu behandeln. zwei wochen später wurde ein -minütiger osce-test (objective structured clinical examination) anhand einer kleinkindpuppe mit den klinischen zeichen einer meningokokkensepsis durchgeführt. im osce war gefordert, eine körperliche untersuchung und diagnostische/therapeutische maßnahmen durchzuführen. anhand einer checkliste mit items wurde geprüft (maximal zu erreichende gesamtpunktzahl , - punkte je item). verglichen wurde die im osce erreichte gesamtpunktzahl und die punktzahl der einzelnen items mittels t-test. die osce-prüfer waren hinsichtlich der gruppenzuordnung geblindet. ergebnisse. die simmed-gruppe erreichte im osce-test signifikant mehr gesamtpunkte (mw , ; sd± , ) als die campus-gruppe (mw , ; sd± , ; p< . ). insbesondere bei den therapeutischen maßnahmen wie volumengabe und kortikosteroidgabe erreichten die studierenden der simmed-gruppe bessere ergebnisse. bei den diagnostischen maßnahmen, wie auskultation, blutdruckmessen, sauerstoffsättigung messen zeigte sich kein signifikanter unterschied zwischen den gruppen. diskussion. die ergebnisse dieser studie zeigen, dass die schulung am simmed-tisch eine geeignete möglichkeit darstellt, das theoretisch erworbene wissen in konkrete handlungen bei einer patienten-simulation umzusetzen (abb. p - ). s. meyer , s. gottschling , e. tutdibi , l. gortner , i. oster universitätsklinikum des saarlandes, klinik für allgemeine pädiatrie und neonatologie, homburg, deutschland, universitätsklinikum des saarlandes, klinik für kinder-und jugendmedizin, zentrum für kinderschmerztherapie und palliativmedizin, homburg, deutschland, unversitätsklinik für kinder und jugendmedizin gebäude , homburg, deutschland, universitätskinderklinik homburg, homburg, deutschland hintergrund. die verwendung von komplementär-und alternativmedizin (cam) findet bei pädiatrischen patienten mit bösartigen erkrankungen nicht selten statt. patienten und methodik. fallbericht. ergebnisse. hier berichten wir über einen -jährigen jungen mit einem metastasierten ependymom, bei welchem es im rahmen einer cam-behandlung zu einer schweren iatrogenen zyanidvergiftung gekommen war. klinisch imponierte ein encephalopathisches krankheitsbild mit agitation und einer schweren initialen bewusstseinsstörung (gcs: ) . die bei aufnahme durchgeführte blutgasanalyse zeige eine schwere metabolische azidose mit ausgeprägter laktaterhöhung. nach intensiver befragung der eltern berichteten diese über die inanspruchnahme von cam-therapien. hierbei wurden über einen zeitraum von rund einer woche tägliche infusionstherapien sowie orale gaben mit soge-nanntem "vitamin b " durchgeführt. nach gabe von natriumthiosulphat kam es zu einer raschen besserung der klinischen symptomatik ohne auftreten von residuen. die toxikologische bestimmung der serumzyanidkonzentration ergab einen hochpathologischen befund. schlussfolgerung. bei kindern, bei denen es zum auftreten eines akuten encephalopatischen krankheitsbildes kommt, sollte differenzialdiagnostisch an eine iatrogene zyanidintoxikation gedacht werden. diese kann im rahmen einer cam-therapie mit amydalin und aprikosenkernen auftreten. hintergrund. ein substratmangel, wie hypoxie oder hypoglykämie, können cerebral zum zellschaden oder gar zelluntergang führen. nach schwerer perinataler asphyxie kommt es bei reifen neugeborenen typischerweise zu einer parenchymschädigung im bereich der basalganglien. weniger bekannt ist aber, dass durch einen mangel an glucose, im gehirn verursachte schädigungsmuster, welches so bei reifen neugeborenen vorkommt. durch bildgebende verfahren ist jedoch ein unterschied der beschädigten cerebralen areale, je nach substratmangel, festzustellen. kasuistik. wie berichten von einem reifen weiblichen neugeborenen der . ssw. die geburt erfolgte mittels vakuumextraktion. postnatal fielen bis auf eine kleine ve-marke keine weiteren auffälligkeiten auf. am dritten lebenstag zeigte sich das kind in der geburtsklinik zunehmend schlapp und trinkfauler bei gleichzeitig bestehender hyperbilirubinämie. aufgrund eines serum-bilirubinwertes von mg/dl wurde das kind zur weiteren therapie auf unsere neonatologische intensivstation überwiesen. bereits im verlauf des transportes kam es zu einem generalisierten tonisch klonischen krampfereignis. der erste gemessene blutzucker bei ankunft lag bei mg/dl. nach glucose-bolus und dauerinfusion, sistierten die klinischen zeichen einer hypoglykämie und die blutzuckerwerte waren im verlauf stets im normbereich. ein erweitertes neugeborenen screening zum ausschluss einer gluconeogenesestörung oder anderer ursachen einer postnatalen hypoglykämie oder stoffwechselstörung war unauffällig. das initiale aeeg zeigte ein anfallsgeschehen. im mrt zeigten sich parietooccipital bilaterale diffusionsrestriktionen und eine verminderte mark-rindendifferenzierung. auch im verlauf konnte bis auf die anamnestisch berichtete malnutrition keine ursache für die hypoglykämie gefunden werden. schlussfolgerung. in der neonatalperiode kann eine protrahierte, nicht erkannte und zu spät therapierte hypoglykämie zu einer irreversiblen okzipitalen parenchymschädigung des kindlichen gehirns führen. warum es ausgerechnet in dieser region bei hypoglykämie in der neonatalperiode zu einem lokalisierten zelluntergang kommt, bleibt unklar. results. neonates with normal mdi or mild disability show significantly lower wms, gms and cs compared to infants with moderate or severe mental disability at year corrected age. the same is true for pdi at year corrected age for wms, gms and cs and years corrected age for wms and cs. conclusion. there is currently not much evidence with regard to the relevance of topography of injury when trying to predict long-term outcome in preterm infants with ivh. the proposed score might serve as a prognostic tool with regard to the severity of brain damage and longterm neurological outcome in preterm infants with ivh. gestational age related reference values in preterm infants < weeks of gestation for the amplitude-integrated eeg using the burdjalov score introduction. the amplitude-integrated eeg (aeeg) is becoming more important to monitor brain activity in premature infants. studies have shown that early aeegs correlate with later neuro-developmental outcome. various scoring systems and missing gestational age related reference values for the aeegs complicate the comparison of published data. the aim of our study was to establish gestational age related reference values for the aeegs using the burdjalov score in preterm infants < weeks of gestation. methods. preterm infants [gestational age (ga) < weeks of gestation] who had an aeeg within the first days of life were retrospectively included into the study. the aeegs had been analyzed using the burdjalov score [continuity (co), cyclicity (cy), amplitude of lower border (lb) and bandwidth span and amplitude of lower border (b)] and correlated with the gestational age. results. the analysis of aeegs showed increasing total burdjalov scores at higher ga. the subscores [continuity (co), cyclicity (cy), amplitude of lower border (lb) and bandwidth span and amplitude of lower border (b)] also increased with increasing ga. conclusion. gestational age related reference values for the burdjalov score were determined in preterm infants < weeks ga. increasing total burdjalov scores correlate with increasing ga. background. hypoxic-ischemic injury (hi) to the developing brain occurs in in live births and remains a major cause of significant morbidity and mortality. a large number of survivors have long-term sequelae including seizures and neurological deficits. however the pathophysiological mechanisms of recovery after hi are not clearly understood and preventive measures or clinical treatments are non-existent or not highly effective in the clinical setting. sildenafil as a specific pde inhibitor leads to increased levels of the second messenger cgmp and has the ability to promote neuroprotection. objective. in this study we investigated the effect of sildenafil treatment on activation of histological recovery and neurogenic response after an ischemic insult to the developing brain. methods. -day-old c bl/ -mice were subjected to sham-operation or underwent ligation of the right common carotid artery followed by hypoxia ( %) for minutes. animals were administered either a single dose of sildenafil ( mg/kg, ip) or received multiple doses on consecutive days starting h after hypoxia. animals treated with vehicle served as controls. furthermore pups received brdu ( mg/kg, daily) from p to p and were either perfusion-fixed at p for immunohistochemical analysis or brains were dissected and h after hypoxia and analyzed for cgmp by means of elisa. results. based on cresylviolet staining, single and multiple sildenafil injections revealed no differences in histological injury compared to sham animals. in addition animals treated with sildenafil showed no increase in brdu positive cells in the striatum. nevertheless doublecortin x as a marker for neuronal precursor cells, was enhanced after sildenafil therapy. furthermore cgmp was enhanced after sildenafil therapy. here we report that single or multiple treatment with sildenafil after hi showed no improvement in histological brain injury or promotion of cell proliferation but enhanced neuronal precursors. our results suggest involvement of the cgmp signaling pathway after hi and contribute to a better understanding of neonatal hi. background. hypoxic-ischemic injury (hi) to the developing brain occurs in in live births and remains a major cause of significant morbidity and mortality. a large number of survivors have long-term sequelaes including seizures and neurological deficits. however the pathophysiological mechanisms of recovery after hi are not clearly understood and preventive measures or clinical treatments are nonexistent or not highly effective. sildenafil as a specific phosphodiesterase- (pde ) inhibitor leads to increased levels of the second messenger cgmp and has the ability to promote neuroprotection. objective. in this study we investigated the effect of sildenafil treatment on activation of intracellular signaling pathways, especially the involvement of the pi /akt and gsk- β pathway after an ischemic insult to the developing brain. methods. -days-old c bl/ -mice were subjected either to shamoperation or underwent ligation of the right common carotid artery followed by hypoxia ( %) for minutes. animals were administered sildenafil ( mg/kg, ip) or vehicle hrs after hypoxia and brains were dissected or h after sildenafil injection. pde expression was analyzed using pcr and pkg-i, p-akt, p-gsk- β and β-catenin were quantified using western blot analysis. results. here we show that the expression of pde in injured animals is decreased at and h. animals treated with sildenafil, who underwent hi showed no further difference compared to controls. furthermore pgsk- β is increased after hi at h. sildenafil enhanced p-akt in treated animals whereas there was no detectable difference in pkg-i and β-catenin levels. conclusions. although pkg-i and β-catenin were not upregulated at h, our data suggest that sildenafil activates the pi /akt signaling pathway through pde inhibition. einleitung. rm sind die häufigsten herztumore im kindesalter und meist mit einer tuberösen sklerose assoziiert. in der regel zeigen sie ein gutartiges verhalten mit einer spontanen regredienz nach der geburt. sie können jedoch auch zu intrakardialen stenosen und/oder arrhythmien führen, die einer spezifischen therapie bedürfen. everolimus wird seit einigen jahren erfolgreich in der behandlung cerebraler tumoren bei kindern mit tuberöser sklerose eingesetzt. kasuistik. bei einem männlichen feten waren multiple kardiale rm festgestellt worden, die während der schwangerschaft ein deutliches wachstum zeigten. der größte tumor füllte das cavum des linken ventrikels nahezu vollständig aus. eine tuberöse sklerose wurde genetisch gesichert (mutation im tsc -gen). nach ausführlicher aufklärung und beratung der eltern erfolgte die geburt spontan beim gestationsalter von + ssw (gg g, gl cm, na-ph , ) in einem perinatalzentrum. die postnatale anpassung verlief regelrecht (apgar / / ). nach anlage eines nabelvenenkatheters und beginn einer dauerinfusion mit alprostadil wurde das neugeborene im alter von stunden in unsere klinik verlegt. klinisch war das kind stabil. auskultatorisch war ein / -systolikum nachweisbar. obwohl dopplersonographisch nur eine milde flussbeschleunigung von , m/s im linksventrikulären ausflusstrakt (lvot) messbar war, wurde aufgrund des morphologischen befundes mit dem potential einer vollständigen obstruktion des lvot u.a. die indikation zur chirurgischen resektion diskutiert. mit dem einverständnis der eltern wurde stattdessen am . lebenstag ein therapieversuch mit everolimus begonnen. die erhaltungsdosis für den angestrebten serum-talspiegel von - ng/ml lag bei mg/m /d. zusätzlich wurden prophylaktisch trimethoprim-sulfamethoxazol und nystatin gegeben. unter der behandlung kam es zu einer raschen und deutlichen größenregredienz der tumore. die infusion mit alprostadil erfolgte bis zum . lebenstag; der ductus arteriosus verschloss sich spontan. die behandlung mit everolimus konnte nach tagen beendet werden. klinisch wurden keine nebenwirkungen beobachtet. laborchemisch war eine leichte hypertriglyceridämie nachweisbar. in der durchflusszytometrie zeigte sich eine lymphopenie mit verminderter anzahl von b-zellen sowie cd -und cd -positiven t-zellen. bei entlassung am . lebenstag war der knabe in sehr gutem allgemeinzustand. ein herzgeräusch war nicht mehr nachweisbar. bei den nachuntersuchungen über einen zeitraum von wochen konnte ein erneutes tumorwachstum ausgeschlossen werden. schlussfolgerung. die behandlung mit everolimus führte bei unserem patienten zu einer regredienz eines riesigen rm im linken ventrikel, die erheblich schneller verlief als sie im rahmen des spontanen verlaufs zu erwarten gewesen wäre. ein komplizierter herzchirurgischer eingriff konnte vermieden werden. die dokumentierten immunologischen nebenwirkungen sollten sich im verlauf zurückbilden. möglicherweise ist die behandlung mit everolimus auch für patienten mit therapiepflichtigen kardialen rm geeignet. eine seltene differentialdiagnose der pulmonalen hypertonie: diffuse kapilläre pulmonale hämangiomatose key: cord- -hmzoxqu authors: alibrahim, omar s.; heard, christopher m.b. title: extracorporeal life support: four decades and counting date: - - journal: curr anesthesiol rep doi: . /s - - - sha: doc_id: cord_uid: hmzoxqu extracorporeal membrane oxygenation (ecmo) or extracorporeal life support (ecls) is a form of heart lung bypass that is used to support neonates, pediatrics, and adult patients with cardiorespiratory failure for days or weeks till organ recovery or transplantation. venoarterial (va) and venovenous (vv) ecls are the most common modes of support. ecls circuit components and monitoring have been evolving over the last years. the technology is safer, simpler, and more durable with fewer complications. the use of neonatal respiratory ecls use has been declining over the last two decades, while adult respiratory ecls is growing especially since the h n influenza pandemic in . this review provides an overview of ecls evolution over the last four decades, its use in neonatal, pediatric and adults, description of basic principles, circuit components, complications, and outcomes as well as a quick look into the future. ecmo or ecls has been around for more than four decades. ecls, which is the name better describes this technology, is a modified form of cardiopulmonary bypass that is used to support patients with cardiopulmonary failure unresponsive to conventional treatment. ecls is performed to drain blood from the venous system, remove carbon dioxide (co ), add oxygen (o ) through an artificial lung (the oxygenator), and return the blood using a pump to the body via an artery as in va ecmo or a vein as in vv ecmo [ ••, - ] . it is important to recognize that ecls is a support modality but not a cure. it provides time for other diagnostic and therapeutic measures to be pursued allowing injured organs to recover meanwhile abundance of oxygenation and optimum tissue perfusion is guaranteed. ecls is a complex, invasive, highrisk, and costly technology, and it should only be conducted in centers with sufficient experience, knowledge, and expertise in that field. the use of silicone rubber membrane in the 's [ , ] provided a strong framework until kolobow perfected the development of the silicone membrane oxygenator in the 's [ ] . this invention allowed the prolonged use of the heart lung bypass machine by clinicians outside the operating room. several groups were working on this concept in the 's and 's. dr. bartlett and bioengineer drinker successfully applied ecls in the laboratory for days using the newly developed membrane oxygenator with lower heparin dosage to minimize bleeding. dr. bartlett, who is considered by many as the father of ecmo, moved to the university of california at irvine in , where he continued to do his work in the laboratory to optimize cardiopulmonary bypass for prolonged use. in , dr. hill reported the first successful use of ecls in a young adult who suffered from severe hypoxic respiratory failure secondary to motorcycle accident in santa barbara, california [ ] . same year, dr. bartlett performed the first successful use of va ecmo on a baby who suffered from low cardiac output syndrome immediately after mustard atrial baffle operation for transposition of great vessels. the first neonatal respiratory survival was not reported until when drs bartlett and gazzaniga successfully used va ecmo for a full-term newborn who was suffering from severe hypoxic lung disease thought to be secondary to meconium aspiration (ma) [ ] . in , dr. bartlett and colleagues published their experience in the use of ecmo for newborn respiratory failure [ ] . he described the use of ecmo in moribund newborn infants; patients survived. all were deemed unresponsive to conventional therapy. the right atrium (ra) and the aortic arch (aa) were cannulated via the internal jugular vein (ijv) and the carotid artery (ca), respectively. primary diagnoses were hyaline membrane disease, sepsis, and persistent fetal circulation including congenital diaphragmatic hernia (cdh) and ma. this paper concluded that ecmo use has decreased mortality and morbidity in newborn respiratory failure, and that ecmo may be used effectively in older patients with respiratory failure if used before irreversible lung damage occurs. this report was a milestone in the evolution of ecmo around the world. many clinicians took notice and came to michigan to learn ecmo. they took this technology back to their hospitals which lead to the widespread use of ecls globally especially in neonatal respiratory failure. va and vv ecls are the most commonly used modes of support [ ••, , , , . va ecls provides cardiac and pulmonary support. therefore, this can be used in ards patients suffering from cardiac or circulatory failure as in severe septic shock. it is the ideal mode of support in cases of severe cardiogenic shock (e.g., cardiomyopathy, myocarditis). support can be partial or total depending on site of cannulation, size and position of the cannulae used, and the native cardiac function. oxygen delivery (do ) is the amount of oxygen delivered to the tissues each minute. it equals the oxygen content times the cardiac output. the more blood diverted to the ecls circuit (maximum cardiac output) with the presence of normal hemoglobin (maximizing oxygen content); do is maximized. va ecls cannulation can be done using one of three access points: first by using the transcervical approach, placing the venous cannula in the ra via the right ijv and the arterial cannula in the aa via the right ca. it is important to assure that the tip of the arterial cannula is away from the aortic valve as this can damage the valve and hinders the myocardial recovery. this approach may provide - % extracorporeal support as part of the blood volume still passes through the patient's native heart and lung. the second approach is the central or transthoracic approach with direct venous cannula placement in the right atrial appendage and arterial cannula placement in the aa. this approach is typically used in postoperative cardiac patients once they fail coming off cpb. this may provide total ecls support as the ecls circuit captures all blood volume and none passes through the native heart. it also has been described in patients with severe septic shock [ ] . the third approach is cannulating the femoral artery and the femoral vein. this approach has been described in adults and older children and has been used in cases of emergency cannulation or extracorporeal cardiopulmonary resuscitation (ecpr). va ecls provide circulatory support. in most cases, inotropes and vasopressors are weaned off soon after ecls initiation. coronary perfusion is provided by retrograde flow via the arterial cannula, which emphasizes the importance to have its tip accurately placed in the aortic arch away from the aortic valve. on the other hand, va ecls requires accessing and mostly ligating the carotid artery. there is an increased risk of systemic embolization with potential end organ damage mainly brain strokes. left ventricular afterload is increased, which may hinder myocardial recovery. vv ecls is ideal for pulmonary support in cases of severe respiratory failure. it does not provide cardiac nor circulatory support. blood is typically drained from the venae cavae and retained to the right atrium. that can be done either by multisite cannulation; usually by draining from a venous cannula in the inferior vena cava via the femoral vein and returning to the ra via the ijv; or single-site cannulation with the use of a double lumen catheter, draining the blood from the venae cavae and returning it to the ra. currently, most of venovenous access is achieved by cannulating the right ijv using a double lumen catheter, which minimizes the problem of recirculation that dominates the multisite access approach. other than sparing the carotid artery and minimizing the risk of systemic embolization especially embolic strokes [ ] , the benefits of vv ecls for pediatric respiratory ecls are evident. the pulmonary blood flow is maintained in vv ecls with well-oxygenated blood, which is considered a great vasodilator of the pulmonary circulation that leads to reduction of pulmonary vascular resistance (pvr). as a result, the afterload of the rv will decrease, augmenting its systolic and diastolic function. these effects continue through to the left side of the heart as the lv preload is optimized and coronary perfusion is maintained with highly oxygenated blood. there is no increase in lv afterload, and the risk of "myocardial stun" in minimized, with resulting improvement in myocardial oxygen delivery and myocardial performance [ , ] . other modes of ecls support are used. venovenoarterial or vva ecls has been increasingly used as a hybrid between va and vv ecls. this is typically used in older pediatric and adult patients with initial va ecls using femoral vein and artery. coronary and upper body perfusion may be inadequate. this can be overcome by adding another venous cannula in the ra via the ijv and connecting it via a y-connection to the returning "arterial" limb, so oxygenated blood is returned to the ra, passes through the native heart to perfuse the coronaries, the carotid arteries and the upper body, meanwhile providing circulatory support via the femoral arterial access. arteriovenous or av ecls is not commonly used in pediatrics. this method can be very effective for co removal utilizing only - % of the cardiac output. the femoral artery and vein are accessed; blood flows through a membrane lung (oxygenator) without a pump using the gradient difference between the arterial and venous pressures. this method, also known as the extracorporeal co removal (ecco r), is ideal for adults with chronic obstructive pulmonary disease (copd) with exacerbation and patients with near-fatal asthma where hypercapnia is the main problem [ , ] . the circuit is usually very simple which potentially makes it safer to maintain. vascular access and cannulae placement has evolved over the years. open surgical technique using the neck vessels and through the chest have been the main traditional methods especially for va support in neonates and young children with cardiorespiratory failure. percutaneous cannulation is becoming more popular and is currently considered the standard of care for vv ecls in pediatrics and adults using the current double lumen cannulae and for va support when accessing the femoral vein and artery. the open surgical approach provide the advantage of visualizing the vessel(s), estimating the appropriate-size cannula, and placement under vision. however, this approach is more time consuming, can lead to more bleeding at the site, and in many instances, requires ligation of the distal end of the vessel [ ••] . percutaneous techniques is faster, may decrease the risk of surgical site bleeding, no distal ligation of vessel is required, and provides a simpler way of decannulation without the need to explore the cannulation site or ligating the vessel. the semi-open technique or the percutaneous-assisted technique has been described especially for vascular access in neonates requiring vv support using double lumen catheter. a small transverse incision is made just above the right clavicle, the right ijv is visualized and then a percutaneous approach is used by accessing the vein cm distally using seldinger technique. transthoracic cannulation is used as an extension of cardiopulmonary bypass if the patient is not able to come off bypass in the operating room. the chest is open via median sternotomy; cannulae are placed directly in the ra and the aorta. decannulation is the procedure that is needed to terminate ecls. cannulae that are surgically placed have to be removed by exploring the surgical site, carefully pulling them out while maintaining homeostasis and ligating the vessels. cannulae placed percutaneously can be withdrawn at the bedside with pressure applied over the site for - min. there is no need for vessel ligation. however, percutaneously placed arterial cannulae may need surgical exploration and vessel repair. ecls circuit designs differ among institutions, although the main components and principles are similar. these components experienced significant evolution especially over the last decade [ •, •] . roller head (semi-occlusive) pumps have been traditionally used in ecls. they are similar to the pumps used in cpb. the blood is squeezed forward through the tubing "the raceway" against a plate at two pressure points in the pump housing while the roller head is rotating. this provides continuous forward motion of the blood towards the oxygenator and then back to the body. these pumps depend on gravity for the venous drainage into the pump (preload), so the patient has to be at a certain height ( - cmh o) from the pump and the bladder reservoir for it to work. whenever there is an interruption to that flow either secondary to hypovolemia, pleural or pericardial tamponade pathology, or kinking in the tubing; the pump will just slow down or stop till the venous return is reestablished or the cause of the problem is corrected. newer pumps have servo-regulation capabilities that allow the ecls specialists to set the alarms so the pump will slow down once certain negative venous (access) pressures are reached. this allows the specialist to troubleshoot and address the problem preventing many interruptions and stoppage of pump flow [ , •, fuhrman, ] . the centrifugal pumps are also used for ecls support. they are used in most pediatric and all adult patients ecls supported. many centers have transitioned from roller head to centrifugal pumps over the last years. centrifugal pumps are non-occlusive. earlier designs used spinning rotor with bearings and seals that lead to excessive head generation. those pumps needed to be replaced frequently, adding to the morbidity and mortality of these patients. with advancement in technology, the newer pumps utilize magnetic levitation to suspend and spin the impeller. their blood-handling qualities have also improved, minimizing heat generation that lead to reduction in circuit related hemolysis and air cavitation. the blood enters these pumps at the apex and gets expelled at the base towards the membrane oxygenator. other advantages include easy set up, small priming volume, ability to trap air and debris within the vortex, and lack of dependency on gravity for blood drainage. these pumps can be placed at any level relative to the patient, which make them suitable for inter and intrahospital transport. the membrane oxygenator, also known as the artificial lung, is responsible for gas exchange in ecls. the kolobow silicone membrane oxygenator was, for decades, the only available gas exchange device in the market. it was constructed of a flat, reinforced silicone membrane envelope that is wound in a spiral coil around a polycarbonate spool. there was a highly gas-permeable barrier separating blood and gas compartments, with no direct blood-gas interface. gas transfer occurs by molecular diffusion as it does in the human lung. the silicone membrane oxygenator was effective in gas exchange, but its compact design created long blood path and high resistance that made it harder to de-air and more challenging to prime. a separate blood warmers (heat exchanger) was needed for most of these devices. it was not unusual to replace these devices during ecls or to need more than one oxygenator to support older pediatric and adult patients. the silicone membrane oxygenators are not available in the market anymore. these hurtles lead to the development of newer generation of devices, the hollow fiber oxygenators. these devices consist of micro porous material where gas exchange takes place by bulk gas transfer via a direct gas to blood interface. these devices are easy to prime, have low resistance, and provide efficient gas exchange. but the longevity of these devices is limited, plasma leak into the gas phase would occur as early as few hours from ecls initiation, that lead to early failure of these devices and the need to be replaced urgently. in the early s, a newer design of these devices became available [ ] . these new devices incorporate the advantageous characteristics of the membrane oxygenator and the hollow fiber oxygenator together using polymethylpentene (pmp) and polyurethane fibers. the pmp is a micro porous material that is very efficient in gas exchange for extended period of time. these devices are durable and may attenuate the inflammatory response during ecls initiation. they have low resistance to blood flow, which makes them easy to prime, reducing the potential for thrombus formations and oxygenator failure. the rated flow is a measure that is used to describe the function of all gas exchange devices. the rated flow, which is the amount of normal venous blood that can be raised from to % oxyhemoglobin saturation in a given period of time, is high which allows many centers to use onesize device for all patients regardless of their size and weight [ , •] . neonatal ecls ( - days) neonates are still compromise the majority of patient population supported by ecls. as of july extracorporeal life support organization's (elso) report, a total of , neonates were supported by ecls, the majority ( , ) with severe respiratory failure with a survival rate of % [ ] . the most common diagnoses are meconium aspiration syndrome (mas), cdh, sepsis [ ] , persistent pulmonary hypertension of the newborn, and respiratory distress syndrome. mas used to be the most common diagnosis till recently. in the early 's, other treatment options such as high frequency ventilation (hfv), surfactant, and inhaled nitric oxide (ino) became more available [ ] [ ] [ ] . it is believed that the increasing use of these therapies has led to the significant reduction of ecls use in this patient population [ , , , ] especially in neonates with mas. there were around neonatal ecls runs reported every year for the last years compared to almost annual cases in the early s. the use of neonatal ecls peaked in with a total of neonates that year from approximately centers around the globe. va ecls is still the most common mode used in neonates, followed by vv ecls using the double lumen cannula [ ] . therapeutic hypothermia during neonatal ecls did not result in improved outcome up to years of age [ ] . in contrast to neonatal respiratory ecls; neonates requiring ecls for cardiac reasons have poorer survival rate of % [ ••] . mortality in neonates with congenital heart disease requiring ecls has not significantly changed over the last - years, despite the dramatic increase in its use for that purpose [ ] . in a recent study, low body weight, single ventricular physiology, lower ph before ecls, and longer time from intubation and mechanical ventilation to ecls deployment were associated with increased mortality in neonates requiring ecls for cardiac indications. mortality in this category is similar in surgical and nonsurgical patients. this data highlighted the importance of early initiation of ecls before acidosis and organ dysfunction occur [ ••, , ••, , ] . this concept was described previously; there is no welldefined criteria defining the optimal timing of ecls initiation in this population. cdh occurs in about : live births. the presence of pulmonary hypoplasia may result in pulmonary hypertension (phtn) with hypoxia, hypercapnia, and acidosis that could be evident soon after birth. variety of ventilation strategies and other treatment modalities (e.g., ino) may be needed in the first few days of life [ ••, ] . ecls have been used for more than three decades in cdh patients with phtn unresponsive to maximum conventional therapy. va and vv ecls have been used effectively; however, va ecls is more commonly used as it unloads the rv that may aid in restoring myocardial function. looking at elso data, cdh mortality did not change significantly over the last two decades. overall, the reported survival rates for cdh and ecls is about - % [ ] . as in other neonatal ecls, the oxygenation index (oi) has been used to determine need for ecls support. oi more than for more than h is considered an indication for ecls. pre-ecls factors (e.g., apgar score, pao , pco , ph) failed to predict outcome or prognosis [ ••] and clinicians should reevaluate selection criteria for not offering ecls to this selected group of patients. the timing of defect repair of ecls-managed patients is controversial. there are two main groups, on or off ecls. surgery performed during ecls can be either early in the ecls course or when phtn is resolved just before decannulation. a review of over cases from the cdh study group (cdhsg) registry [ ] over a -year period evaluated the outcome of surgery either during or after ecls. taking into account other outcome-associated variables such as duration of ecls run, type of surgical repair, and patient factors, patients repaired post ecls had a significantly better outcome. the odds of dying were . times greater if the repair was performed during ecls. this may be associated with a reduced bleeding risk as well as bias towards patients who have improved more quickly allowing ecls decannulation. the ability to wean off ecls within a two-week period may contribute positively to the outcome with respect to the timing of surgery [ ] . if the patient was weaned off ecmo within weeks, surgical correction post ecmo was associated with a significantly better outcome and a significantly reduced risk of bleeding when compared to patients at that institution who were repaired on ecls. the early repair on ecls has been suggested to offer the benefit of surgery before the anasarca becomes extensive and allows recovery from the physiologic insult while on ecls, hopefully without prolonging the ecls duration. a review of repair within days of ecls [ ] demonstrated that the risk of bleeding at surgical site was < %, the operative repair took less than h with a survival rate of %. other ecls-related bleeding complications were no different from those reported to the elso registry. anticoagulation management during ecls for cdh is pivotal especially if cdh repair is performed during ecls run. a review of atiii use in (target activity > %) cdh ecls patients [ ] when compared to the institutions historical control demonstrated that the use of atiii lead to significant reduction in the utilization of ffp, packed red cells, and platelets in the first days of ecls. the use of large volumes on blood products may adversely affect lung mechanics and delay recovery. amicar and tranexamic acid used peri-operatively could be helpful to minimize bleeding. pulmonary hypoplasia is an important component with respect to the need for ecls support related to hypoxia and hypercapnia. there have been case reports on the use of perfluorocarbons (pfc) to support alveolar maturation. a prospective randomized study of cdh patients on ecls [ ] with or without pfc use evaluated lung growth using l vertebral body size for comparison. there was about % increase in the left (affected) lung size during the pfc use. there were no noted side effects or complications from the pfc use. however, there was no comment on the lung growth in the non pfc group, and mortality was not significantly different (small n = ). viral and bacterial pneumonia causing acute respiratory failure and acute respiratory distress syndrome (ards) are common causes of morbidity and mortality in the picu. ecls has been successfully used as a rescue therapy for these patients unresponsive to conventional methods [ ] [ ] [ ] [ ] . as of july , a total of , pediatric patients received ecls, with patients supported for respiratory indications with a survival rate of % (elso) and in one report up to % [ ] . patients with respiratory syncytial virus infection, aspiration pneumonia, and near-fatal asthma [ ] has better chances to survive while those with ards related to sepsis, pertussis, fungal pneumonia, disseminated herpes simplex virus infection, immunodeficiency, multiorgan failure, and longer duration of mechanical ventilation (> days) before ecls deployment have higher odds of mortality [ , , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . pre-ecls severe acidosis in addition to renal failure and need for continuous renal replacement therapy (crrt) have been related to lower survival, longer ecls duration, and higher complication rate [ , ] . ecls utilization in pediatric population has slightly increased over the last - years [ , ] . this increase has been steadier since with a total of cases reported that year, later peaked in with pediatric ecls in total. this increase is believed to be due to expanding the inclusion criteria for this patient population [ , ] , increase use of ecls in patients after congenital heart surgery, widespread of use of vv ecls, the advancement and the use of double lumen cannula in children, in addition to the expansion in extracorporeal cardiopulmonary resuscitation (ecpr) use [ , ] . conditions and comorbidities like immunosuppression, malignancy, and sepsis are considered acceptable indications for ecls these days, but would have been contraindications to ecls - years ago [ , , , [ ] [ ] [ ] [ ] [ ] [ ] . patients are more complex with more comorbidities. paden et al. [ ] reported an increase in pediatric ecls comorbidities from % in to % in . recent reports showed that pediatric ecls patients with malignancies and immunodeficiency could have a reasonable outcome with a survival rate - % [ , , ] . patients with bone marrow (bmt) and stem cell transplant present a particular challenge. gow et al. [ ] showed ecls survival rate of % based on the elso registry data in . of those four patients who survived ecls in that study, only one patient was able to leave the hospital. the development of renal failure and multiorgan dysfunction were considered risk factors for death. there are few case reports that described successful use of ecls in bmt and stem cell transplant patients secondary to different etiologies [ ] . the decision to offer ecls in this patient population should be on a case-by-case basis. providers should take into consideration the overall patient prognosis from the underlying illness, assess the presence of multiorgan dysfunction and understand the family wishes for their loved ones before considering ecls as an option. va support has been for many years the mode of choice for pediatrics respiratory ecls [ ] . it is still the predominant mode found in the elso registry. the utilization of vv ecls is gaining popularity in pediatrics [ , , , , ••, ] . in , vv ecls cases outnumbered va ecls cases in pediatric respiratory indications. now, in , vv ecls is considered the standard of care in pediatric patients with severe respiratory failure unresponsive to conventional therapies. pettignano et al. [ ] reported the early successful use of vv ecls for this patient population. eighty patients received ecls in his center over a period of years ( - ) . sixty-eight patients received vv ecls with a survival rate of % compared to va ecls patients with a survival rate of %. the cannulation techniques for vv ecmo in pediatrics have also evolved over the last years. multisite venovenous cannulation was the preferred method used in pediatric respiratory ecls. the continued advancement of vvdl, especially in the late 's when the bicaval wire-reinforced catheters was approved by the food and drug administration, single-site cannulation using these cannulas became a common practice [ ••, ] . in , vvdl cannulation for vv ecls represented % of the total cannulation. the use of vvdl cannulas have provided improved vv ecls pump performance with evidence suggesting reduction of the risk of recirculation traditionally related to the multisite approach. these cannulas can be inserted percutaneously, but need to be performed under imaging guidance to avoid the risk of atrial perforation or disruption to the hepatic vein [ , ] . using fluoroscopy, ultrasonography, or a combination of both is recommended. ards in adults is well described in the literature with high rates of morbidities and mortality that can exceed %. many conventional methods were studied to minimize this risk with mixed results [ ] . ecls use in adults with ards was first described in with dr. hill's experience. this was followed by the first multicenter randomized trial of the use of ecls in adults with ards conducted by zapol et al. [ ] at the national institute of health (nih) in . the results were disappointing as the mortality rate was > %. this put the brakes on using ecls for adult population for two decades. in , dr. bartlett and colleagues [ ] described their experience at the university of michigan in the largest retrospective study discussing the use of ecls in adult patients with ards between and with a survival rate of %. a protocol-driven algorithm was used in their institution since guiding the treatment of severe ards including the use of ecls. while on ecls, lung rest strategies, minimal anticoagulation, and optimization of oxygen delivery were the key factors. these results were encouraging, and ecls was perceived again as a viable and successful option for adults with ards not responsive to maximum conventional therapy. this regained confidence in adult respiratory ecls was boosted by the encouraging results of the cesar trial (efficacy and economics assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure) by peek and colleagues in the uk [ ] . this study showed improved survival rate without disability at months after discharge from the hospital ( vs %; rr= . ; ci . - . , p = . ) in adult patients with ards transferred to ecls center. sixty-eight patients were supported by ecls of whom ( %) survived. as considered by many, the real rebirth of adult respiratory ecls occurred in . this milestone was driven by two major events: the influenza a (h n ) pandemic and by the availability of adult-size bicaval dual-lumen cannula. these cannulae are inserted percutaneously using seldinger technique under ultrasound or fluoroscopy in the right ijvand positioned to allow drainage of venous blood from the venae cavae and reinfusing to the ra. looking at the elso registry, there were less than reported cases of adult respiratory ecls per year, with then a substantial increase in with cases. this increase continued and peaked in with cases. more than % of the total runs in these reports are venovenous ecls mode (vv, vvdl, and vvdl-v) with overall survival rate of % [ ] . patients with viral or bacterial pneumonia, asthma, and trauma are more likely to survive [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . longer duration on mechanical ventilation before ecls, multiorgan failure, central nervous system (cns) events, fluid overload [ , , ] , non-pulmonary infections, higher peak inspiratory pressures, acidosis (ph < . ) and higher paco are associated with poor outcome. interestingly, the use of neuromuscular blockade and prone positioning before ecls was favorable. this initial experience of adult respiratory ecls with h n -induced ards came from australia and new zealand [ ] with survival rate up to % at the end of the study period. other reports from other countries came out describing their experience during the h n pandemic in adults with variable result, but mostly with survival rates - % [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the review of these reports revealed the importance to emphasize on the fact that ecls is a complex, high-risk, and costly technology, and it should only be conducted in centers with sufficient experience, knowledge, and expertise in managing ecls. as a result, a position paper [ ••] was published in july by an international group of physician and health care providers in order to provide physicians, care providers, hospital administrators, and policy makers a description of the optimal approach to organizing ecls program for adults with respiratory failure to ensure safety and proficiency. vv ecls using the bicaval dual-lumen cannula is the most common practice in adult respiratory indications [ , ] . ecls flow of - l/min would be ideal to provide adequate oxygenation and ventilation for an adult with severe ards. additional venous drainage cannula (usually in the femoral vein) may be warranted to achieve this goal. arterial oxygen saturation more than % would be acceptable given that clinical and laboratory evidence of adequate oxygen delivery to the tissues is achieved. ecco r is a modality of extracorporeal support that is increasingly utilized in adult respiratory population when hypercapnia is the main drive behind the need for excessive minute ventilation and ecls support. ecco r allows the use of low blood flow ( . - l/min) via a pumpless device to remove co efficiently. this typically is achieved by av support accessing the femoral artery on one side and the femoral vein on the other side. this approach is ideal for patients with copd exacerbation and hypercapnia. once on vv ecls or ecco r, patients can soon be placed on minimal ventilator settings "rest settings," continuous positive airway pressure (cpap), or even get extubated to protect their lungs from further injury [ ] [ ] [ ] . early tracheostomy provides patients with less discomfort and allows early mobilization that would be beneficial to facilitate recovery. early mobilization and rehabilitation is considered mandatory while patients on vv ecls as a bridge to lung transplantation [ , [ ] [ ] [ ] . there are few contraindications for ecls that include advanced age, severe disability (wheelchair bound), intracranial bleeding, uncontrolled coagulopathy, mechanical ventilation more than a week with high peak pressure and oxygen requirements [ ] . the use of ecls in pregnancy is uncommon; there are significant concerns regarding bleeding, fetal demise, and thrombotic complications. pregnant women with h n infection have higher risk of mortality and morbidity compared to nonpregnant women [ ] . over the last few years, especially during the h n influenza pandemic, there have been many reports of successful ecls use in pregnancy or postpartum period related to ards [ , , , •] . in the case series from australia and new zealand [ ] , they reported the use of ecls in pregnant thirty-one reports were found, reports of va ecls and of vv ecls with a total of patients. overall maternal survival rate was % while fetal survival was slightly lower than %. most common indications were severe ards, postpartum cardiogenic shock, and amniotic fluid embolism. in one case, delivery by cesarean section was performed during ecls; otherwise, delivery of the fetus was deferred. anticoagulation management was conservative maintaining lower therapeutic levels of activated clotting time (act) and activated partial thromboplastin time (aptt). the author recommends using act levels - s and aptt - s. there were few cases with mild to moderate amounts of postpartum vaginal bleeding with one case of catastrophic hemorrhage. the most common bleeding sites were around tracheostomy and ecls cannulation sites. the use of ecls in pregnancy is controversial. there are no guidelines for its use in this patient population yet, however recent reports over the last years showed that ecls has been successfully used in pregnancy and postpartum patients for cardiopulmonary failure with good maternal and fetal outcomes. ecls seems to be underutilized in this patient population. careful patient selection and cautious anticoagulation management can reasonably minimize bleeding risk. acute hypoxic respiratory failure and ards secondary to trauma is well recognized and is associated with high mortality and morbidity. pulmonary contusions occur in % in these patients. reid et al. [ •] reported their experience over years (april to april ) utilizing ecls for respiratory indications in trauma patients. fifty-two patients were included in that review with moderate to severe head injury in ( %) cases. all patients had multiple traumas and most of them ( %) had rib fractures with hemothorax and pneumothorax. thirty-one percent of these patients underwent surgical procedure while on ecls. vv ecls and ecco r were the main modes of support. their overall survival rate was %. out of the patients with intracranial bleeding, ended up with an external ventricular drain and three underwent craniotomies. multiorgan failure was the major cause of mortality; only one patient suffered from catastrophic bleeding and one with severe brain damage who eventually died. other reports [ , ] including more recent study by guirand et al. [ ] supported the use of ecls mostly by vv support in trauma ards patients with favorable outcomes. ecls is still considered the most common form of mechanical circulatory support in patients with cardiac failure unresponsive to conventional therapies. cardiac ecls has been consistently growing among different age groups over the last few years [ , , ••, , ] . as of july , a total of , cardiac ecls cases reported at the registry with an overall survival rate of . %, with % in neonates, % in pediatrics, and % in adults (elso). most of these patients (> %) is supported by va ecls either via cervical or central cannulation, the later being more common in the immediate post-operative period in neonates. pediatric patients with myocarditis have the best chances to survive (up to %). cardiac ecls is provided as a mean to organ recovery or as a bridge to transplant. newer devices like ventricular assist devices (vad) are more durable. its use for cardiac support is growing over the last years. vads are smaller and simpler devices compared to ecls, which allows early mobilization. ecpr is defined as applying ecls during cardiac arrest while performing cardiopulmonary resuscitation, or when repetitive arrest events occur without return of spontaneous circulation for > min [ ] . as of july , there are cases of ecpr reported to the elso registry with in neonates, in pediatrics, and in adults with overall survival rate of % ( % in neonates and pediatrics and % in adults) [ ] . the use of ecpr has increased over the years [ ] . pre ecpr acidosis, prematurity, and complication during ecls (crrt, intracranial bleeding, persistent metabolic acidosis) are associated with increase odds of death, while cardiac disease (e.g., arrhythmias, myocarditis) and neonatal respiratory illness are associated with improved outcome [ , , ••, , ] . recent reports showed the increasing use of ecpr in adult population with a trend towards decreased survival in recent years ( %). ecpr practice is institution dependant and it has been mainly limited to cardiac icus and for in-house arrest only. there have been few reports of ecpr use for out-of-hospital cardiac arrest with documented survival and intact neurological outcome [ , ] . the extracorporeal life support organization (elso) was founded in (https://www.elso.org). it is an international non-profit consortium of health care centers and individuals who are dedicated to the development, evaluation, and improvement of ecls. elso maintains the world's largest registry of data on ecls patients, with voluntary submission of this data. it provides elso centers with biannual reports on center-specific as well as worldwide number of cases, outcomes, and complications. other functions of elso include providing data for quality assurance and research, which has been growing. there are just fewer than , ecls publications listed in pubmed as of january . it also publishes the elso redbook, which is considered the definitive reference for ecls. elso has been partnering with its global chapters (euroelso, asia-pacific elso, latin american elso, and south and west asia elso) to advance ecls support internationally. there are published guidelines that are available for public describing useful and safe ecls practice; these guideline are revised regularly. bleeding is still a major complication during ecls. forty-six mechanical and patient related complications are recorded through the registry every year. oxygenator failure is the most common mechanical complication. table summarizes the most common events reported to elso as of july [ ] . ecls patient management is complex. it starts with patient selection and initiation of ecls. this is a large topic to cover in this context, so for that reason; we will briefly cover four major areas: ventilator management, anticoagulation, fluid and nutrition, and neurological management. understanding the role of ecls in respiratory indications is the key. it is important to mention that ecls is a support modality not a cure. it provides efficient gas exchange using an artificial lung, allows time for ecls providers to treat the underlying lung disease and prevent further iatrogenic lung injury. gentile ventilation is a very important principle in respiratory ecls. using high pressures trying to "open the lungs" is a dangerous maneuver that can lead to further lung injury and poor outcomes [ ] . applying lung "rest settings" on the ventilator should occur within the first few hours after initiation of ecls [ •] . this can be achieved in many formats. conventional ventilation using synchronized intermittent mandatory ventilation (simv) pressure control (pc) with pressure support (ps) is one way. minute ventilation will be brought down to a minimum. pc of cmh o above positive end expiratory pressure (peep) with a rate of , peep of - cmh o and ps of - is acceptable as long as the peak inspiratory pressure (pip) stays below and never exceeds cmh o. in addition to being protective of further iatrogenic lung injury, the use of this mode allows the providers to prevent any swings in pip that may occur using a volume control mode and enable them to objectively calculate the dynamic compliance of the lung as a measure of daily progress. hfov can also be used during ecls. it can be advantageous in cases of severe air leak syndrome, severe pulmonary edema, and pulmonary hemorrhage. it is important to minimize the minute ventilation and bring ventilation settings (amplitude and frequency) to a minimum. mean airway pressure should be kept below cmh o and never exceeds . it is uncommon to maintain patients on hfov during ecls course; its use could make it difficult to perform pulmonary toilet, assess tidal volumes, and patient might need heavy sedation. airway pressure release ventilation (aprv) or bi-level mode can be used emphasizing the same principles. p high can be set at - cmh o as long as the total pressures stay below cmh o and never exceeds . t high (time allowed for p high to be delivered) can be extended ( - s) to guarantee further recruitment as patient can breathe spontaneously during this. cpap with ps is a modality that is more acceptable now especially in awake patients with or without tracheostomy. patients, especially adults, can be extubated early in the ecls course. pulmonary toilet is pivotal in managing these patients, by frequent suctioning of mucous plugs and secretion. bronchoscopy should be used liberally for that purpose. saline installation in the endotracheal tube can facilitate that. other materials like pulmozyme and perfluorocarbon liquid have been used with variable results. the interaction between the blood and the biomaterials of the ecls circuit can lead to unwarranted effects by activating platelets and coagulation factors that promotes thrombosis and consumptive coagulopathy [ ] . as a result, using anticoagulation therapy is needed. the use of unfractionated heparin (ufh) has been the gold standard. it is cheap, available, has a short half-life, and can be reversed with protamine sulfate if needed. on the other hand, ufh is an indirect anticoagulant; it works by potentiating antithrombin (at) effect to inhibit "free" thrombin; it does not inhibit clot-bound or circuitbound thrombin. monitoring and managing anticoagulation therapy during ecls is challenging especially in neonates and young children. laboratory monitoring is typically done act has been, for decades, the most commonly used routine whole blood test [ ] . it measures how many seconds that takes a blood sample to form a clot. it is inexpensive, and can be performed quickly at bedside test, but it is not specific and provides a general idea about coagulation. for example, a prolonged act (> ) could indicate thrombocytopenia, platelet dysfunction, consumptive coagulopathy, excessive heparin, or a combination of these events. more detailed testing is needed to determine the next appropriate action [ ] . acceptable range is - s. that can be lower ( s) if there are concerns about bleeding. aptt is a plasma-based test that measures time to fibrin formation. it has been an acceptable mean to titrate anticoagulation therapy, and there is decent experience among providers, but it could show a lot of variability, and its use in critical conditions might be questionable [ ••] . acceptable range of . - . x patient baseline or - s is reasonable. anti-xa assay (heparin level, heparin assay) is a plasmabased test that measures the ufh effects based on its ability to catalyze at inhibition on factor xa. appropriate anti-xa levels of . - . unit/ml correlate well with ufh effects and showed to minimize blood sampling, blood products transfusions with less bleeding and clotting complications. thromboelastogram (teg) is another whole blood point of care test that examines the clot formation, strength, and fibrinolysis. it is not widely available; there is an element of subjectivity to the results interpretation, and there is limited data on improved outcomes with its use. direct antithrombin inhibitors' use has been documented in ecls in cases of heparin induced thrombocytopenia (hit) or heparin resistance. bivalirudin and argatroban have been used with some promising results [ , ] . for more details on this topic, please visit elso website-guidelines https:// www.elso.org/resources/guidelines.aspx. optimal sedation and analgesia during ecls remains poorly defined. many studies have demonstrated the need to escalate sedation requirement during ecls [ ] [ ] [ ] [ ] [ ] . fentanyl and morphine [ ] are the most commonly used opioids in ecls. escalation of these medications have been documented and attributed to an increase in the volume of distribution, increased sequestration in the circuit tubing and oxygenator, and decreased metabolism, at least in the case of morphine use [ ] , to its active metabolites. the use of benzodiazepine (e.g., midazolam and lorazepam) and dexmedetomidine [ , ] are common practices in different age groups. dexmedetomidine is an α- adrenergic receptor agonist that has analgosedative effects that may facilitate weaning heavy sedation. it is not uncommon for ecls patients to be heavily sedated during the first few days. the use of muscle relaxation is commonly used in cannulation, decannulation, and during procedures. it should not be a routine practice. nondepolarizing agents are commonly used in picu settings including ecls patients when necessary. these agents can be used as continuous infusion (e.g., cisatracurium, atracurium, vecuronium) or bolus dosing (rocuronium, vecuronium). cisatracurium is considered an appropriate agent to use in ecls patients because of its reasonable recovery time once turned off ( - min), safety profile, and ability to use in patients with multiorgan failure. cisatracurium is eliminated by ester hydrolysis and hofmann elimination. it is recommended to perform regular neurological examination on heavily sedated patients early in their course once or twice a day by lifting off the muscle relaxation and possibly reducing the sedation infusion. the goal of minimizing sedation while maintaining comfort is ideal. non-medical maneuvers including child life support, music, playing games, reading books, and family involvement play a major role in caring for these patients with less sedation, less withdrawal, and faster recovery. frequent neurological examination is critical during ecls. intracranial complications especially during va ecls are serious [ ] [ ] [ ] . clinicians should be vigilant, performing neurological assessments daily. a sudden unilateral change in the diameter of one pupil should prompt an aggressive investigation for an acute intracranial pathology especially bleeding. serial head ultrasound can be performed at the bedside for neonates and young infants receiving ecls to assess for intracranial abnormalities. adequate nutrition is pivotal for recovery in critical illness. enteral nutrition, even at trophic amounts, is preferred [ ] to maintain gut integrity, reduce risk of bacterial translocation and risk of tpn-related cholestasis, but total parenteral nutrition can be used if needed. maintaining strict fluid balance in ecls patients is crucial. fluid overload has been associated with increased mortality [ , ••] . it is not unusual to require large volume of fluids at the initiation of ecls, but clinician should be proactive instead of reactive in fluid management. the use of diuretics, concentrating medication infusion, and the judicious early initiation of ultrafiltration and crrt has proven to reduce ecls duration and length of stay [ , , , ] . ecls or ecmo is an acceptable mode of support in neonates, pediatrics, and adults with acute cardiorespiratory failure unresponsive to conventional therapies with an overall survival of %. the use of ecls is growing especially in adult respiratory indications, and will continue to grow. bleeding is still one of the most challenging complications. the development of new devices over the last few years resulted in a much simpler, safer, and prolonged ecls support. new styles of patient management including minimal sedation, spontaneous breathing, early tracheostomy, and early mobilization are becoming more common. the next generation of ecls devices will be easier to manage by caregivers, less thrombogenic, and more durable with less or no need for systemic anticoagulation. as per dr. bartlett, these are the highlights of the next era in ecls care "ecmo iii." conflict of interest omar al-ibrahim and christopher m.b. heard declare they have no conflict of interest. human and animal rights and informed consent this article does not contain any studies with human or animal subjects performed by any of the authors. wb saunders. neonatal ecmo has resulted in significant improvement the survival of neonates with cardiorespiratory failure unresponsive to conventional therapy 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growing rapidly. ecls care is complex, high risk and costly modality. adult ecls should be conducted in centers with experience extracorporeal membrane oxygenation for respiratory failure in adults contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era emerging indications for extracorporeal membrane oxygenation in adults with respiratory failure extracorporeal life support for adults with severe acute respiratory failure active rehabilitation and physical therapy during extracorporeal membrane oxygenation while awaiting lung transplantation: a practical approach concept of "awake venovenous extracorporeal membrane oxygenation" in pediatric patients awaiting lung transplantation extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. american journal of respiratory and critical care medicine h n influenza virus infection during pregnancy in the usa pandemic (h n ) influenza, pregnancy and extracorporeal membrane oxygenation extracorporeal membrane oxygenation for severe ards in pregnant and postpartum women during the h n pandemic modern use of extracorporeal life support in pregnancy and postpartum ecls use in well-selected pregnant and postpartum patients appears to be safe and associated with encouraging maternal and fetal survival rate with low complications ):r . the use of vv ecls and pumpless (av) in patients with acute respiratory failure and severe thoracic trauma represents an excellent support modality traumatic lung injury treated by extracorporeal membrane oxygenation (ecmo) application of ecmo in multitrauma patients with ards as rescue therapy venovenous extracorporeal life support improves survival in adult trauma patients with acute hypoxemic respiratory failure: a multicenter retrospective cohort study extracorporeal membrane oxygenation to support cardiopulmonary resuscitation in adults extracorporeal membrane oxygenation to aid cardiopulmonary 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children: clinical article brain injury associated with neonatal extracorporeal membrane oxygenation in the netherlands: a nationwide evaluation spanning two decades positive fluid balance at day of adult ecls is an independent predictor of -day mortality. that may reflect disease severity continuous renal replacement therapy with an automated monitor is superior to a free-flow system during extracorporeal life support enhanced fluid management with continuous venovenous hemofiltration in pediatric respiratory failure patients receiving extracorporeal membrane oxygenation support key: cord- -oujgcciq authors: gupta, ena; awsare, bharat; hiroshi, hitoshi; cavarocchi, nicholas; baram, michael title: don’t drive blind: driving pressure to optimize ventilator management in ecmo date: - - journal: lung doi: . /s - - -y sha: doc_id: cord_uid: oujgcciq introduction: driving pressure (dp) while on ecmo has been studied in acute respiratory distress syndrome (ards) but no studies exist in those on ecmo without ards. we aimed to study association of mortality with dp in all patients on ecmo and compare change in dp before and after initiation of ecmo. methods: consecutive patients placed on ecmo either veno-arterial ecmo or veno-venous ecmo between august and february were reviewed. the outcomes were compared based on dp before and after ecmo initiation. results: a total of patients were included: ( %) had ards while ( %) did not. there were individuals for whom dp was available, ( %) had a decrease in dp, whereas ( %) had an increase in dp and ( %) had no change in dp after ecmo initiation. those with an increase in dp had a higher initial peep ( vs cm h( )o, p < . ) and a higher peep decrease after ecmo ( . cm h( )o vs by . cm h( )o, p < . ). those with an increase in dp had a significantly longer stay on ecmo than those without (p = . ). on multivariable analysis, higher dp h after ecmo initiation was associated with an increase in -day mortality (or . , % ci . – . , p ≤ . ). conclusion: a significant proportion of patients experienced an increase in driving pressure and decrease in compliance after initiation of ecmo. higher driving pressure after initiation of ecmo is associated with increased adjusted -day mortality. individualized ventilator strategies are needed to reduce mechanical stress while on ecmo. the past decade has seen an increased utilization of extracorporeal membrane oxygenation (ecmo) as a life sustaining strategy for respiratory and/or cardiac failure [ ] . veno-venous (vv)-ecmo is used to provide temporary gas exchange support in patients with primary respiratory failure and preserved cardiac function. however, veno-arterial (va)-ecmo is used for temporary circulatory assistance in patients with cardiogenic shock or refractory cardiac arrest. despite the increasing use, optimal management of mechanical ventilation on ecmo is not well established [ ] . research has focused on indications, timing, and outcomes in patients requiring ecmo; however, there are no large randomized control trials focusing on a preferred mechanical ventilatory strategy during ecmo. ecmo support theoretically allows for a reduction in intensity of mechanical ventilation. the resultant decrease in lung stress and strain permits lung rest with potentially improvement in outcomes. ultra-low tidal volume ventilation for lung protection is well accepted as best practice during ecmo [ ] . however, how best to achieve this remains unclear. an international survey of all elso-registered ecmo centers showed a huge variability in the approach to mechanical ventilation during ecmo for acute respiratory distress syndrome (ards) [ ] . the majority of these centers ( %) reported "lung rest" to be the primary goal of mechanical ventilation, whereas % reported "lung recruitment" to be their ventilation strategy. various trials of ecmo have also used variable settings in both the treatment and control arms. this variability may impact outcomes in ecmo-supported patients. there has been mounting evidence of the direct relationship of mechanical power applied to the lung and worsening injury [ ] . however, a safety limit or the ideal titration method is unclear. in ards, driving pressure (dp) has emerged as a target to adjust tidal volume and peep to limit cyclic and dynamic strain during mechanical ventilation. several retrospective studies following the initial analysis by amato et al. have found dp as the variable that is most associated with mortality in ards [ ] . even though there are no prospective studies for dp as a target for ventilator management, it has consistently been replicated, is physiologically sound and easily measured at the bedside, making dp an increasingly accepted target for monitoring during mechanical ventilation in ards. however, dp while on ecmo has not been well studied. one retrospective study of ards patients by cheu et al. has shown that dp during first days of ecmo initiation was an independent predictor of mortality [ ] . also, even though dp is a term defined for ards, individuals requiring va-ecmo support for cardiac failure are also at risk for atelectrauma and barotrauma, and dp may play a role in the ventilation in the setting of pulmonary edema due to acute cardiac failure. prolonged mechanical ventilation while on ecmo support makes this group highly susceptible to ventilator-induced lung injury. there are no studies evaluating role of driving pressure in this subset of ecmo patients. we aimed to study driving pressures before and after initiation of ecmo to compare groups with increase and decrease in driving pressure and their outcomes. we also aimed to study association of dp with mortality in patients on both va-and vv-ecmo. we hypothesized that a shift to ecmo would lead to a decrease in driving pressure as it allows for ultra-lung protective ventilation. in conjunction, higher driving pressure while on ecmo would be associated with higher mortality. a retrospective study was performed including all the patients placed on either va-or vv-ecmo between august and february at our tertiary care referral center. patients who were cannulated at an outside facility and transferred to our hospital were also included. those who had ecmo duration shorter than h from cannulation were excluded in this study. the local institutional review board for human research approved this study (irb # d ) and the need for informed consent was waived due to the retrospective nature of the study. before consideration of ecmo initiation, all patients were sedated and ventilated with lung protective ventilation based on the mechanism of their disease process, arterial blood gas, and ventilator mechanics. the decision to initiate ecmo was made by the treating intensive care specialist [ ] . majority of patients received the rotaflow pump (n = , %), whereas ( . %) received biomedicus and ( . %) received the cardiohelp pump for ecmo cannulation. initial mechanical ventilator setting protocol after ecmo support was as follows: tidal volume - ml/ kg pbw; peep - cm h o; peak inspiratory pressure - cm h o; respiratory rate - breaths per minute; and fio adjusted to maintain arterial oxygen saturation above %. plateau pressure was measured by performing an end inspiratory hold maneuver on the ventilator. dp was calculated as the plateau pressure minus peep. static respiratory system compliance was measured by tidal volume divided by dp. murray score was calculated before and after ecmo initiation to stratify severity of acute lung injury [ ] . data were collected retrospectively on baseline characteristics, comorbidities, ards status, severity of illness score like apache ii score among all included ecmo patients. information regarding the ecmo circuit and ventilation parameters before and after initiation of ecmo was also recorded. data collected included duration on ecmo, death on ecmo, status at hospital discharge, and status at days after termination of ecmo. all individuals who had dp measured both before and after initiation of ecmo were identified. among those individuals, change in driving pressure was calculated as dp after ecmo minus dp before ecmo. group a was defined as those who had an increase in dp and group b was defined those who had a decrease in dp h after initiation of ecmo. those with no change in driving pressure were not included in this analysis. we described baseline characteristics of all patients on ecmo by ards status. categorical variables were reported as numbers (percentages) and continuous variables as means ± standard deviation. single-variable comparison was performed by student t test for continuous variables and chisquare or fisher exact tests for categorical variables. we then compared ventilatory parameters before and after initiation of ecmo by ards status. we performed single-variable and multivariable logistic regression analyses to evaluate association of driving pressure on ecmo with -day mortality in all patients. known risk factors for mortality were included in the regression model for adjustment. we adjusted for age, sex, va/vv-ecmo, days in the hospital before ecmo initiation, steroid use before ecmo, and cardiac arrest. odd's ratio (or) was expressed with % confidence interval (ci) and p value less than . was considered to be significant. we also performed comparative analyses of characteristics and outcomes between groups a and b. analyses were conducted in stata . (stat corp, college station, texas). a total of patients including ( . %) with ards and ( . %) with no ards were reviewed. a majority of ards patients (n = , . %) were on vv-ecmo and a majority of non-ards patients (n = , . %) were on va-ecmo. a schematic distribution of the study population is shown in fig. . the indication for ecmo initiation is listed in table for both va-and vv-ecmo. the patient's characteristics are shown in table based on the presence or absence of ards. patients with ards were younger and had a higher bmi. no difference seen in apache ii score between those with ards and without ards. before staring ecmo, individuals were ventilated with an average peep of . cm h o and average plateau pressure of . cm h o. both plateau pressure and peep were higher in those with ards than those without ards before initiation of ecmo as shown in table . plateau pressure and peep decreased significantly after initiation of ecmo in both ards (p < . ) and non-ards individuals (p = . ). however, dp showed no change in both ards and non-ards after initiation of ecmo. murray score among those without ards was . ± . before ecmo and . ± . after ecmo indicating a mild/moderate lung injury. further comparisons of ventilatory parameters before initiation of ecmo and h after ecmo among ards and non-ards patients are shown in table . overall outcomes in the entire cohort of ecmo patients comparing those with ards and those without ards are shown in table . the overall -day mortality of the entire study cohort was %. the -day mortality was higher in those without ards as compared to those with ards ( % vs %, p = . ). in single-variable analysis, higher dp on ecmo was associated with an increase in odds of -day mortality (or . , % ci . - . , p = . ) among all ecmo patients. this association was significant among those with ards (or . , % ci . - . , p = . ) and those without ards (or . , % ci . - . , p = . ). on multivariable analysis, higher dp on ecmo was significantly associated with an increase in mortality after adjusting for age, sex, va/vv-ecmo, days in the hospital before ecmo initiation, steroid use before ecmo, cardiac arrest (or . , % ci . - . , p ≤ . ). among the individuals for whom dp was available both before and after ecmo, group a (those with increase in dp) consisted of patients ( %), group b (those with decrease in dp) consisted of patients ( %), and the rest ( %) had no change in dp after ecmo initiation. table shows comparisons of the groups of the patients. group a had ( %) patients with ards and ( %) without ards as compared to ( %) with ards and ( %) without ards in group b. group a had a significantly longer stay on ecmo than group b ( ± days in group a vs ± . days in group b, p = . ). this trend was similar among those with ards ( ± days in group a vs ± . days in group b, p = . ) and those without ards ( ± days in group a vs ± . days in group b, p = . ). death on ecmo and -day mortality was not significantly different between the two groups (table ). in this study, % of patients had an increase in driving pressure (group a) after initiation of ecmo. these patients were more likely to be on vv-ecmo as compared to va-ecmo. they also had a significantly higher drop in peep as compared to those in group b (p < . ). all patients on ecmo in our institution were ventilated at a tidal volume of cc/kg ibw. the increase in driving pressure after ecmo is likely related to a protocolized application of ventilator settings including lower peep after initiation of ecmo. this implies that those maintained on high peep setting before ecmo were also ventilated with peep between and cm h o leading to decrease in compliance and increase in driving pressure. both groups had a similar initial static compliance, but group a had a lower compliance after ecmo. this decrease in compliance is likely due to an increase in atelectasis and decrease in lung recruitment. even though ultra-lung protective ventilation while on ecmo is protective against barotrauma, there may be an increased risk of atelectrauma due to under-recruitment. alveolar o tension decreases rapidly in an atelectatic lungs [ ] leading to alveolar hypoxia, a potent inducer of lung inflammation [ ] . atelectasis can therefore lead to worsening of ventilator-associated lung injury. these factors apply to patients on vv-or va-ecmo. in our study, those without ards were also noted to have a decreased compliance and an elevated murray score. patients on va-ecmo have risk factors including cardiogenic pulmonary edema, postoperative lung damage, and thoracic compliance reduction after cardiac surgery making them susceptible to worsening lung injury and ards. hence, atelectrauma can have deleterious consequences in both ards and non-ards patients. in this study, those with an increase in driving pressure after ecmo had a significantly longer length of ecmo stay as compared to those with a decrease in driving pressure. along with the mechanisms of lung injury and atelectrauma described above, it is also possible that those with underrecruitment have slower weaning due to worse oxygenation on weaning trials and also worse appearance of radiological abnormalities due to atelectasis impacting decision to wean by physicians. although this group had higher initial peep which could represent higher severity of illness, initial compliance was similar in both groups and decreased after ecmo in this group with an increase in driving pressure. this highlights the importance of individualizing peep for adequate recruitment especially for those with severe disease requiring high initial levels of peep. some patients especially those on va-ecmo and right heart failure can be adversely affected by high peep [ , ] . caution must be experienced in these patients and merits of high peep must be balanced with deleterious effects of positive pressure on right heart. on the other hand, patients with left heart failure on va-ecmo who have a propensity for pulmonary edema may benefit from higher peep [ ] . this further supports the fact that if ultra-lung protective ventilation is applied it should be applied with higher peep [ ] . a recent study showed that near apneic ventilation in a pig model of acute lung injury supported by ecmo when compared to conventional protective ventilation decreased driving pressure by % and reduced mechanical power times [ ] . this resulted in less histologic lung injury and metalloproteinases activity as compared to conventional protective ventilation or non-protective ventilation. therefore, reducing intensity of mechanical ventilation by reducing mechanical power and driving pressure is essential for prevention of ventilator-induced lung injury [ , ] . in our study, a higher driving pressure on ecmo was an independent predictor of -day mortality in both unadjusted and adjusted analysis among all patients on ecmo. driving pressure has previously been shown to be an independent predictor of mortality in ards patients [ ] , however, has not been evaluated in non-ards patients. pham and colleagues also showed, in a cohort of patients with influenza a(h n )-induced ards, that a higher plateau pressure on the first day of vv-ecmo for acute respiratory failure was significantly associated with icu death (odds ratio = . , % confidence interval = . to . , p < . ) [ ] . our study further demonstrates that ventilation during ecmo may have an impact on mortality in both ards and non-ards patients. overall mortality among all patients with ecmo was %, higher among non-ards ( %) than those with ards ( %). this is because the non-ards patients include patients on va-ecmo due to post-cardiotomy failure, acute myocardial infarction, and post-cardiac arrest including those who received cardiopulmonary resuscitation ( %) before ecmo. we acknowledge the limitations of this study. the retrospective nature of analysis lends itself to misclassification and bias. also, we only collected mortality information at days after ecmo termination and no long-term outcomes were assessed, although we consider this short-term mortality as relevant and more directly related to the variable of interest, i.e., mechanical ventilation on ecmo. secondly, we acknowledge that this is a very heterogenous group of patients as this includes all patients on ecmo including ards and non-ards patients. these groups have differences in their lung mechanics and different pathophysiological risks for lung injury. we note ventilatory parameters and murray scores before and after initiation of ecmo but lack serial measurements of volume status or wedge pressures among those without ards. however, we showed that driving pressure was associated with mortality in both the subgroups of ards and non-ards patients. third, we did not have direct information on the tidal volumes used in these patients. our institution protocol mandated tidal volume of - ml/kg ibw for patients on ecmo; however, we are unable to evaluate protocol deviations in this cohort. also, initial driving pressure before ecmo initiation is not available for all patients. this is due to the high volume of patients transferred from outside hospitals for ecmo or cannulated at an outside facility for ecmo. these patients did not have full ventilator mechanics recorded before ecmo. in spite of these shortcomings, this study is unique in evaluating driving pressures in both va-and vv-ecmo population and one of the first studies to compare at driving pressure before and after initiation of ecmo. current elso guidelines published in now recommend using peep as high as tolerated in the first h of ecmo [ ] . this is a change from the guidelines when no peep recommendations were provided. however, protocol and practices continue to vary. also, there are no set guidelines on driving pressures on ecmo. this study points towards targeting low driving pressure on ecmo in both ards and non-ards patients. more controlled studies are needed to establish exact targets while on ecmo. at our institution, we have now moved away from a uniform application of peep in patients on ecmo and focus on titrating peep based on lung compliance, adequate recruitment, and driving pressure. a significant proportion of the patients had an increase in driving pressure and decrease in compliance after initiation of ecmo despite ultraprotective ventilation. this may be due to inadequate recruitment while on ecmo. those with increase in driving pressure had a longer length of stay on ecmo. elevated driving pressure after ecmo initiation was associated with increased adjusted -day mortality among both va-and vv-ecmo. adequate recruitment with individualized application of peep along with ultraprotective ventilation may improve outcome while on ecmo. author contributions all authors listed have contributed sufficiently to the project to be included as authors, and all those who are qualified to be authors are listed in the author by-line. data availability raw data can be made available on request. trends in u.s. extracorporeal membrane oxygenation use and outcomes mechanical ventilation during extracorporeal membrane oxygenation in patients with acute severe respiratory failure a extracorporeal life support organization: elso guidelines for cardiopulmonary extracorporeal life support and patient specific supplements to the elso general guidelines mechanical ventilation during extracorporeal membrane oxygenation. an international survey near-apneic ventilation decreases lung injury and fibroproliferation in an acute respiratory distress syndrome model with extracorporeal membrane oxygenation association of driving pressure with mortality among ventilated patients with acute respiratory distress syndrome: a systematic review and meta-analysis dynamic driving pressure associated mortality in acute respiratory distress syndrome with extracorporeal membrane oxygenation an expanded definition of the adult respiratory distress syndrome magnitude and time course of acute hypoxic pulmonary vasoconstriction in man hypoxia-induced inflammation in the lung: a potential therapeutic target in acute lung injury? acute leftward septal shift by lung recruitment maneuver monitoring of right-sided heart function high inflation pressure pulmonary edema. respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure mechanical ventilation during extracorporeal membrane oxygenation driving pressure and survival in the acute respiratory distress syndrome ventilator-related causes of lung injury: the mechanical power extracorporeal membrane oxygenation for pandemic influenza a(h n )-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis the authors declare that they have no conflict of interest. key: cord- -yv x viu authors: shekar, kiran; badulak, jenelle; peek, giles; boeken, udo; dalton, heidi j.; arora, lovkesh; zakhary, bishoy; ramanathan, kollengode; starr, joanne; akkanti, bindu; antonini, m. velia; ogino, mark t.; raman, lakshmi; barret, nicholas; brodie, daniel; combes, alain; lorusso, roberto; maclaren, graeme; müller, thomas; paden, matthew; pellegrino, vincent title: extracorporeal life support organization coronavirus disease interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers date: - - journal: asaio j doi: . /mat. sha: doc_id: cord_uid: yv x viu the extracorporeal life support organization (elso) coronavirus disease (covid- ) guidelines have been developed to assist existing extracorporeal membrane oxygenation (ecmo) centers to prepare and plan provision of ecmo during the ongoing pandemic. the recommendations have been put together by a team of interdisciplinary ecmo providers from around the world. recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. this is a living document and will be regularly updated when new information becomes available. elso is not liable for the accuracy or completeness of the information in this document. these guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ecmo specifically, in the context of the covid- pandemic. the tulip bulbs i planted last fall are now blooming red and yellow, and the cherry trees are covered with blossoms. i am elated for mother nature's annual gift, yet i know that this season is already unlike any others. the emergence of severe acute respiratory syndrome coronavirus (sars-cov- ) and the disruption in our routines and expectations have made it spring, interrupted. still, as history teaches us during times of great challenge, we find our heroes. the frontline hospital team members and hospital support staff are performing heroically as the medical community struggles to understand and manage a new illness. despite the many variables and unknowns related to coronavirus disease (covid- ) , extracorporeal membrane oxygenation (ecmo) professionals have faced the challenge of treating the most seriously ill patients with ingenuity and dedication. this guideline exemplifies the priorities of the global ecmo community to share the knowledge gained through our experiences of success and-just as importantly-failure. i am grateful to the extracorporeal life support organization (elso) covid- working group, a collaboration of interdisciplinary ecmo providers from around the world, and the elso staff for their hard work. i also thank the reviewers for lending their time and expertise while leading the fight in some of the most severely affected parts of the world. our hearts go out to the families affected by this unprecedented pandemic. the team of experts who authored the guideline is resolute in defining "best practices" to fulfill our responsibilities to our fellow clinicians, our patients, and their families. in the months and years to come, we will be proud of our response to the call to serve. the resilience of the human spirit will prevail. spring will continue to thrill us. society will adapt and endure. mark t. ogino, md president, elso the world health organization declared the severe acute respiratory syndrome coronavirus (sars-cov- ) outbreak a pandemic on march , . patients infected with the novel virus develop coronavirus disease (covid- ) leading to a significant increase in hospital and intensive care unit (icu) admissions globally. a vast majority of intensive care admissions are due to hypoxaemic respiratory failure with up to % of patients (n = , ) requiring invasive mechanical ventilation in the italian cohort. invasive ventilation rates of - % have been reported in other settings. - a small proportion of these patients fail maximal conventional therapies and may require extracorporeal membrane oxygenation (ecmo) support. as the pandemic has evolved, there has been a steady increase in ecmo use. , at the time of writing this guideline, there were covid- patients supported with ecmo. , (mean age years, % vv ecmo, % va ecmo and other configurations). the pandemic of a novel and highly transmissible respiratory virus is placing significant stress on health care systems around the world. icus are forced to rapidly increase capacity to accommodate a large number of critically ill patients requiring organ support, most notably mechanical ventilation. in this setting, provision of ecmo may be challenging from both resource and ethical points of view. the interim recommendations presented here balance the need to provide high-quality ecmo care to those who may benefit most while being cognizant of available resources and maintaining an environment of patient and staff safety (figure ) . although there is paucity of high-quality evidence to guide ecmo practice in many areas, these recommendations are based on available evidence, [ ] [ ] [ ] existing best practice guidelines, - experience from previous infectious disease outbreaks, [ ] [ ] [ ] [ ] [ ] ethical principles, [ ] [ ] [ ] [ ] [ ] [ ] and consensus opinion from experts. in addition, the extracorporeal life support organization (elso) covid- working group members completed a survey on patient selection criteria for ecmo to build consensus. the guidelines fall into these three categories as follows: recommended: the technique/intervention is beneficial (strong recommendation) or the intervention is a best practice statement. not recommended: the technique/intervention is not beneficial or harmful. consider: the technique/intervention may be beneficial in selected patients (conditional recommendation) or exercise caution when considering this intervention. the guidelines provided here pertain to key areas specific to covid- related cardiopulmonary failure and apply to neonatal, pediatric, and adult patient populations. we refer the readers to existing elso guidelines, the elso red book, published literature, and reliable printed or online resources for additional information regarding the provision and practice of ecmo. the current work is a "living document" developed by the elso covid- working group. the group will remain active for the duration of the pandemic and during any future covid- outbreaks to revise the guidelines as new information and evidence become available. the most up-todate version of the guideline document and all previous iterations can be found on the elso website www.elso.org. we refer readers to published literature , including existing guidelines to assist with organization of ecmo programs outside the context of covid- . • during the pandemic, covid- and non-covid- patients should receive ecmo in established ecmo centers using available resources to maximize benefits. , • we do not recommend the commissioning of new ecmo centers for the purposes of treating covid- patients. • we recommend responsible ecmo use based on system capacity for ecmo. when in crisis capacity (figure ), health care services will be overwhelmed, making resource allocation more challenging and limiting ecmo utilization. resources are dynamic and ecmo centers may transition from conventional to crisis capacity rapidly. • centers should preferentially offer ecmo to patients in whom outcomes are favorable or ecmo runs are relatively short (e.g., meconium aspiration syndrome, near-fatal asthma, non-covid- myocarditis, massive pulmonary embolism, cardiotoxic medication overdose, etc.). • the international cooperation during the covid- pandemic has allowed for real-time communication of clinical experience, data, and outcomes in an unprecedented fashion. ecmo centers are encouraged to submit data to the elso registry to enable accurate reporting of realtime reporting of ecmo utilization during the pandemic and enroll in ongoing studies such as the elso endorsed ecmo for novel coronavirus acute respiratory disease (ecmocard) study led by the asia-pacific elso and the euro elso ecmo survey. • elso chapters should regularly liaise with all relevant industry partners, regional distributors, and local manufacturers to maximize resources and maintain supply chains. • ecmo organization on a national level is encouraged to optimize resource utilization via coordination of government and private supply chains. centralization through existing public bodies such as the united kingdom national health service and private entities such as japan's ecmo network (ecmonet) are crucial. ecmo provision based on system capacity. covid- , coronavirus disease ; ecmo, extracorporeal membrane oxygenation; ecpr, extracorporeal cardiopulmonary resuscitation; icu, intensive care unit; va, venoarterial; vv, venovenous. • we recommend central coordination of ecmo services via regional networks while utilizing existing hub and spoke models of care and ecmo retrieval to service the ecmo needs of the region. when individual institutions are overwhelmed or understaffed, it may be possible to enlist staff from areas with ongoing reserve. • we recommend similar selection criteria be utilized in regional networks to provide equitable care across the programs. • ecmo programs should keep a manifest of all team members who are trained to care for ecmo patients. • regular and frequent communication among ecmo directors and coordinators can help predict and prepare for ecmo needs with the possibility to centrally coordinate resources (personnel and equipment). • the ecmo director(s) should lead the team to ensure consistency in ecmo patient selection and daily patient management at an institutional level. • capacity can be increased by adapting equipment usage and staffing ratios. this will depend on the care model already in use at local hospitals. • coordination and communication between medical, nursing, and allied health staff is critical to quality ecmo outcomes. • ecmo has been mainly used for adult patients with covid- infection. in the event that adult ecmo programs exceed capacity, institutional, local, or regional pediatric ecmo programs can be valuable resources. • we recommend maintaining a : patient: nurse ratio when patients are on ecmo. when capacity is at conventional or contingency tier levels, ecmo specialist ratio should follow institutional norms. • when capacity is at contingency tier and crisis levels, transitioning to a patient: specialist : ratio with the ecmo specialist overseeing more than one circuit whilst maintaining a : bedside nursing ratio may be considered. this may be achieved by cohorting of ecmo patients where possible. • redeployment of perfusionists to bedside ecmo care and reintegration of former ecmo specialists can expand the personnel pool. • teams are encouraged to maintain a senior ecmo specialist without a patient assignment to act as a float for emergency contingency management. • simplification of the ecmo circuit may be used to increase circuit safety and reduce ecmo specialist workload in some settings. examples include omitting negative pressure side pigtails, to reduce the risk of air entrainment, or blood monitoring devices, to reduce the need for calibration samples. any such changes to standard circuitry should be communicated widely to staff. • redeployment of devices previously used in the hospital and familiar to staff can increase capacity. for instance, pumps being used as a paracorporeal ventricular assist device may also be used for ecmo when coupled with a membrane lung. the us food and drug administration has issued guidance to help expand the availability of devices (e.g., cardiopulmonary bypass devices, accessories, and components) used in ecmo therapy to address this public health emergency. • fresh supplies of ecmo circuits and cannulas may be increasingly difficult to obtain. communication through elso with manufacturers may help to identify options for resupply. cardiac surgery and perfusion departments may be able to help with tubing and cannula supplies. • the shelf life of primed circuits may be extended to days to conserve circuitry, provided as follows: ) the circuit is constructed and primed using standard sterile techniques and ) the prime is electrolyte solution-based, and no glucosecontaining solutions or albumin are used within the prime. this may be more relevant to centers with smaller case volume. there is a clear indication of increased mortality with increasing age and comorbidities that should not be overlooked. , specific considerations for patient selection will inherently be different during a pandemic due to a limited capacity to offer this resource-intensive mode of support, and thus the following should be taken into consideration. • as disease burden increases and systems move to escalating levels of surge capacity (contingency capacity tier and beyond), we recommend that selection criteria become more stringent ( table ) to use this resource for those most likely to benefit and return to an acceptable quality of life (figure , refer to "ethics" section). • when decompression of an overwhelmed hospital within a region is needed, preferentially relocate suitable ecmo candidates (young, single organ failure, previously healthy) to available ecmo centers. indications for venovenous (vv) ecmo should not deviate from usual indications per elso and other existing guidelines. we recommend the following additional covid- pandemic considerations for vv ecmo: • we recommend against initiation of ecmo before maximizing traditional therapies for acute respiratory distress syndrome (ards), in particular prone positioning (figure ). • our understanding of ards in covid- is still evolving. there is considerable debate on the "atypical" nature of ards in this patient population , and on best mechanical ventilation strategy including adjuncts to be applied. although ventilation management before vv ecmo initiation may have a significant bearing on outcomes, there is insufficient data to make any specific recommendations for mechanical ventilation strategies in context of covid- ards and as such they are beyond the scope of this work. • if mobile ecmo is unavailable, consider referring patients to ecmo centers "early," such as when partial pressure of oxygen (pao ): fraction of inspired oxygen (fio ) ≤ mm hg. if the decision to transport is made too late, patients may be too unstable for transport. in patients with covid- , the development of multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, pericardial effusions, and venous thromboembolism have been reported in up to % of patients requiring icu care. [ ] [ ] [ ] [ ] elevation in high sensitivity troponin above the th percentile upper reference limit has been reported in % of nonsurvivors as opposed to % of survivors and a continual rise in high sensitivity troponin has been associated with mortality. covid- may also be associated with hypercoagulability, increasing the risk of pulmonary thromboembolism. [ ] [ ] [ ] • indications and patient selection criteria for venoarterial (va) ecmo should not deviate from per existing guidelines. timely provision of va ecmo is recommended before development of multiple organ failure. • consider va ecmo in selected patients with refractory cardiogenic shock (persistent tissue hypoperfusion, systolic blood pressure < mm hg, cardiac index < . l/ min/m , while receiving noradrenaline > . mcg/kg/min, dobutamine > mcg/kg/min or equivalent). • the need for hybrid configuration such as veno-venous arterial (v-va) ecmo (venous drainage with both venous and arterial returns) is relatively infrequent. it may be considered in experienced centers for patients with ards in addition to suspected acute stress/septic cardiomyopathy or massive pulmonary embolism with associated cardiogenic/obstructive shock failing medical therapies. • patients requiring va ecmo support who incidentally test positive for covid- but are not thought to be critically ill due to the virus should be considered for ecmo support in the usual fashion. • we recommend against provision of extracorporeal cardiopulmonary resuscitation (e-cpr) in less experienced centers or centers without an existing e-cpr program before the pandemic. e-cpr in patients with out-of-hospital cardiac arrest is not recommended when systems are experiencing surge situations (contingency capacity > tier ). we recommend against the provision of prehospital e-cpr. • at experienced centers, e-cpr may be considered for highly selected non-covid- patients with in-hospital cardiac arrest depending on resource availability. however, in patients with covid- , the potential for cross-contamination of staff and the use of personal protective equipment (ppe) by multiple practitioners when in short supply should be considered in the risk-to-benefit ratio of performing e-cpr. poor outcomes with conventional cpr have been reported in covid- patient population. • emergency conversion from vv to va ecmo in patients who suffer cardiac arrest during cannulation for vv ecmo may increase risk to staff, is unlikely to result in a favorable outcome for the patient, and is thus not recommended. we recommend the following contraindications for ecmo in patients with cardiopulmonary failure due to covid- (table ) in centers functioning under significant resource constraints, for example, contingency capacity ≥ tier . these recommendations are based on data available from conventionally managed critically ill covid- infected patients admitted to icu and existing ecmo risk prediction models derived from non-covid- patients. - , - data from covid- patients supported with ecmo should soon become available to further guide patient selection. • the cannulation consent process should explicitly involve discontinuation of ecmo care in the absence of recovery of lungs, heart, or both within an acceptable time frame as system capacity allows , or if ecmo is actively harming the patient (e.g., severe bleeding or clotting). • consider performing ecmo cannulation within a designated covid- environment and avoid transfers to catheterization lab or operating rooms where possible. cannulation should be performed by trained cannulators. • a dedicated person should be allocated to medically manage the patient during the cannulation process. we recommend a maximum of five team members in the room/ bedspace during cannulation. cannulation team members should wear standard, contact, and airborne ppe. • awake cannulation is strongly discouraged. we recommend that the airway be secured before cannulation to avoid unplanned emergent intubations during the procedure that may pose an undue risk to staff present. appropriate use of sedation and neuromuscular blockade is recommended during cannulation. • centers should develop a checklist for cannulation and cannulation team members should ensure they take all necessary supplies with them before entering the room. we recommend preparing a cannulation covid- sprinter bag that contains all cannulae, guide wires, fluids, heparin, sterile sleeves for ultrasound probe, etc. • prepare a medication bag and resuscitation trolley outside the cannulation room. we recommend having a dedicated person in full ppe be stationed outside the cannulation room to bring additional supplies as needed. • placement of a mechanical chest compression device beforehand if the patient is expected to deteriorate before cannulation and offering va/v-va ecmo is considered appropriate in those circumstances. • we recommend the use of plain x-ray, vascular ultrasound, and echocardiography (transthoracic or transesophageal) or fluoroscopy over a blind cannulation. , cannulation • we recommend that large multistage, drainage cannula be used (e.g., fr or greater for adults) where possible to minimize the need for insertion of an additional drainage cannula at later stage. we suggest a single stage, return cannula ( - fr for adults). • dual lumen cannulae should be avoided if possible as they take relatively longer time to insert, are associated with higher risk of thrombotic complications and malpositioning requiring repeat echocardiography with associated increased resource utilization and personnel exposure. • we recommend that either the femoro-femoral or femorointernal jugular configuration be used. the femoro-femoral approach allows for more rapid surgical field preparation, creates efficiency of movement around the bed, and keeps the operator away from the patient's airway. • we recommend a femoro-femoral configuration for va ecmo cannulation. a distal limb perfusion catheter is strongly recommended to reduce the risk of limb ischemia. • we suggest placement of three separate single lumen cannulae for the utilization of v-va ecmo and do not recommend the use of a double-lumen cannula for v-va ecmo. • we do not recommend the initiation of v-va ecmo as a preemptive strategy. if a patient requires vv ecmo but has no evidence of cardiac dysfunction or cardiac dysfunction is medically supportable with inotropes, placement of an arterial cannula is strongly discouraged. optimal supportive care on ecmo is critical to ensure positive outcomes. this should be guided by existing evidence and recommendations. offer best practice guidance. ventilator dyssynchrony in setting of a high respiratory drive may lead to secondary lung injury and should be avoided. • centers should follow existing anticoagulation guidelines and institutional protocols with appropriate monitoring and dose adjustments (figure ). • since covid- patients may be associated with a hypercoagulable state, consider targeting anticoagulation at the higher end of normal ecmo parameters. • caution should be exercised when using lower ecmo blood flow rates (< l in adults) given the greater risk of circuit thrombosis in this patient population. • patients with a hypercoagulable status may benefit from antiplatelet agents (such as aspirin, clopidogrel, prasugrel, ticagrelor), but there is little data to recommend or refute. both thrombocytopenia as well as prothrombotic states have been reported in patients with covid- . • patients with covid- may have secondary hemophagocytic lymphohistiocytosis. screening should be considered for this condition, and a hematology service should be consulted for appropriate therapies. • there is no evidence to guide the transfusion thresholds in patients with covid- . • we recommend judicious use of blood products, due to anticipated blood product shortages during a pandemic. reasonable transfusion thresholds may include as follows: hemoglobin (hb) ≥ - gm/dl ; platelet > , /l, and fibrinogen > mg/dl. if there is no clinically significant bleeding, lower platelet counts and fibrinogen concentrations may be tolerated. • routine use of antifibrinolytics is not recommended due to the risk of potential thrombosis in covid- patients, as there have been reports of a hypercoagulable state. • there are emerging reports of convalescent plasma transfusion use in patients with covid- . there is no current evidence for or against such plasma transfusion therapies in patients with covid- supported on ecmo. • we recommend early enteral nutrition (within hours) commencing at low doses and advancing to target over - days. we recommend avoidance of prolonged nutrition deficit where it is anticipated the patient will recover. - • we recommend cautious use of prokinetics (metoclopramide) for delayed gastric emptying due to risk of prolonged qtc interval. • we recommend standard, contact, and airborne precautions if evaluating gastric residual volume, due to the unknown risk of exposure to sars-cov- via gastric secretions. • we recommend standard, contact, and airborne precautions while handling diarrheal stool or vomitus. there is a potential, but currently unknown, risk of sars-cov- transmission from stools or vomitus. a bowel management system may be used. • currently, there is not enough evidence to recommend for or against the use of covid- specific therapies (hydroxychloroquine, azithromycin, steroids, lopinavir/ ritonavir, remdesivir, or tocilizumab). decisions to utilize such therapies should be based on a case-by-case basis. • there is not enough evidence to recommend routine steroids in covid- -associated respiratory failure or ards. steroids may be used in the context of septic shock. , role for cytokine hemadsorption devices • currently, we lack definite evidence to recommend for or against the use of extracorporeal cytokine hemadsorption devices in covid- patients who develop septic shock. additionally, the effect of such devices on drug elimination or virus clearance is unknown. • early mobilization when safe and feasible may help improve recovery and maintain neuromuscular function. however, in the setting of covid- , early mobilization of patients during their ecmo course is unlikely to be feasible at most centers and is of unclear benefit and definite risks, which include as follows: hemodynamic instability, dislodgement of tubes/catheters, availability of resources to facilitate mobilization, and viral transmission. bedside nurses may be instructed on in-bed physical therapy maneuvers in an attempt to maintain standard of care while limiting personnel exposure and ppe use. • judicious decisions regarding the need and timing of procedures is important in covid- patients to avoid unnecessary staff-exposure. • we recommend bronchoscopy only if it can provide diagnostic or therapeutic benefit to the patient (with appropriate ppe required). patients can be made apneic during the procedure to minimize aerosol generation if tolerated. • percutaneous tracheostomy should be performed with caution after careful consideration of risk-to-benefit ratio in an individual patient. • based on current knowledge, existing weaning guidelines • it is anticipated that most va ecmo runs in the context of covid- will bridge to recovery. we recommend the use of existing va ecmo weaning protocols. , • bridge to durable device or to transplant can be challenging in the setting of a pandemic. as such, we recommend that multidisciplinary teams discuss exit strategies before cannulation for va ecmo. family should be involved in the decision-making process along with ethics/palliative teams, if possible. • full ppe precautions should be observed. adequate care should be taken to prevent contact with bodily fluids. • careful assessment of bleeding and thrombotic risks is recommended before decannulation. cannulas placed by cut down should be surgically removed at the bedside, if possible. the risks of aerosol generation during electrocautery is unclear and optimal ppe should be used. • venous cannulae placed by percutaneous access can be removed at the bedside and bleeding controlled by topical pressure or sutures. smaller arterial cannulas (e.g., ≤ fr) placed percutaneously may also be removed nonsurgically through close coordination with relevant surgical teams is recommended. • if adequate resources are available, centers with established mobile ecmo programs should offer ecmo transport to appropriately selected covid- patients. during the covid- pandemic, critically ill patients with cardiorespiratory failure can present at non-ecmo centers and exhaust local resources. societal recommendations include institution of ecmo or referral for ecmo in appropriately selected covid- patients. , as such, programs with established mobile ecmo programs and with sufficient resources to maintain it, should continue to offer this highly specialized therapy to surrounding hospitals. commercial support for transport between sites also exists for areas where local transport is not available. • covid- specific criteria for ecmo cannulation should be extended for mobile ecmo candidates. ecmo application may also be considered to facilitate transport of unstable covid- patients being referred to external hospitals. patients with covid- may require transfer to other centers either for specialized procedures and consultation or due to local resource limitation and bed capacity. although not immediately indicated for ecmo, if such patients are not stable for transport, ecmo deployment may facilitate safe transport. • if performed, ecmo cannulation at remote sites should be performed with full ppe. cannulation of patients at external sites carries a risk of exposure to the transport team and requires strict adherence to ppe precautions. cannulation practices should follow the cannulation guidelines outlined in this document. • all transport team members, including ems personnel and driver or pilot, should have ppe training and wear ppe throughout the ecmo transport. the transport of infectious patients carries significant risk to transport personnel. accidental exposure and contamination, with subsequent quarantine, can lead to strain on already limited personnel and resources. appropriate training has been shown to reduce self-contamination. • minimize aerosol generating procedures (agps) during transport and consider the use of high-efficiency particulate air (hepa) filters on the expiratory limbs of mechanical ventilators. there is no evidence to support the routine use of a viral filter on the exhaust of the commonly used polymethylpentene based ecmo membrane lungs. • develop a plan to disinfect transport vehicles and to manage waste materials generated during transport in accordance with local regulations and in line with transport service providers. • intrahospital transport of covid- patients should be limited to vital diagnostic and therapeutic purposes and appropriate planning and protective precautions should be taken to prevent exposure to staff and other patients. • covid- is not a contraindication to ecmo in this patient population. • we recommend using existing indications and thresholds for consideration of ecmo as per currently published elso guidelines. - some of the covid- specific indications and contraindications are summarized in table . • candidacy for ecmo should be preemptively made before reaching the stage of need for ecmo. this is based on the information that children with covid- admitted to pediatric intensive care unit (picu) are likely to have multiple comorbidities, and this may influence consideration of ecmo support. • e-cpr in pediatric covid- patients with severe ards is likely to have a poor prognosis, poses significant infection risks to staff due to aerosolization and is not recommended. however, ecmo centers may wish to define e-cpr candidacy for in-hospital cardiac arrest upon admission of a covid- positive patient to their unit. • the cannulation consent process should explicitly involve discontinuation of ecmo care in the absence of recovery of lungs, heart or both within an acceptable time frame , or if ecmo is actively harming the patient (e.g., severe bleeding or clotting) • consent process should take into consideration the possibility that the parents/care providers may not be present for a face-to-face discussion. • the ecmo consent should involve the standard components: benefits, risks, and complications but should also refer to the current unavailability of published ecmo outcomes that would guide the length of ecmo run, particularly in the event of no lung recovery or irreversible multiple organ failure. we recommend following standard cannulation techniques. cannulation team members should wear standard, contact, and airborne ppe. • surgery (especially sternotomy and electrocautery) is an agp, and as such, the use of p /n respirators (without valves) along with a smoke evacuation device and eye protection is recommended. powered air purifying respirators (paprs) are highly desirable in this setting. • surgical loupes are not a substitute for protective eyewear and may preclude the use of goggles or face shields. each program will need to determine if surgical cannulation techniques can be performed while maintaining ppe requirements. if not feasible, consideration for exclusive use of percutaneous cannulation should be discussed for patients with suspected and confirmed covid- infection. general supportive measures • management of ecmo in covid- patients is similar to standard ecmo patients. • anticoagulation guidelines as per institutional policy should be followed. higher than usual intensity of anticoagulation may be indicated. a case-by-case assessment of bleeding versus thrombotic risks is recommended pending further evidence. • the role of chest physiotherapy and bronchoscopy during ecmo should be determined on case-by-case basis. inline suction catheters are strongly recommended. • the covid- pandemic may result in a shortage of blood products. we recommend the development of a blood conservation plan which aligns with institutional and blood supply chain emergency/disaster blood supply guidelines. consider the following for your local plan: -restrictive transfusion thresholds, based hb concentration and physiologic metrics and biomarkers of oxygen delivery -reduced frequency of blood tests -a staged approach with phases for immediate introduction of blood conservation strategies and for when fresh product supplies are impacted. • therapeutic plasma exchange and ivig are currently not recommended for covid- patients unless part of a clinical trial. • use of medical therapies such as antivirals/hydroxychloroquine/azithromycin/zinc/vitamin c/steroids in pediatric patients should be individualized, based upon best available evidence at the time and is beyond the scope of this document. • refer to elso weaning guidelines - and ecmo weaning and decannulation in adult patients for covid- specific recommendations (refer to weaning and decannulation section). • although hospitals may be limiting or restricting visitation during the pandemic, neonatal and pediatric patients may benefit from parental presence at the bedside. we recommend one parent, with a maximum of two (depending on local institutional guidelines), be allowed to be present at the bedside. use of videoconferencing to connect with family members or support systems (religious personnel, etc.) may be beneficial. • resource availability and lack of improvement over time may necessitate reassessment of treatment goals and redirection of care. • parents and family members should be made aware of this plan during the consent process. • during a pandemic, pediatric hospitals associated with adult hospitals should reserve ecmo equipment for potential non-covid- neonatal and pediatric ecmo use, taking into special consideration, those diagnoses with historically excellent outcomes when supported with ecmo including but not limited to meconium aspiration syndrome and postcardiotomy support for lesions with good outcomes. for example, anomalous left coronary artery from the pulmonary artery (alcapa). the modes of transmission of sars-cov- are primarily through the respiratory tract and mucous membranes. there is a potential, but currently unknown, risk of sars-cov- transmission from stools or vomitus. all high-risk procedures on ecmo should be performed by experienced staff. key infection control and staff safety measures relevant to ecmo use in covid- infected patients are summarized in tables and . optimal ppe recommendations are subject to change as more data becomes available. patient selection and timing of discontinuation of ecmo support pose significant ethical and moral challenges in regular ecmo care, but especially so during a pandemic. , , ecmo centers should develop predetermined "consensus criteria" encompassing all aspects of ecmo care in covid- patients. in addition, communication with local and regional ecmo and non-ecmo programs would be advantageous in caring for potential covid- patients that would benefit from ecmo support. reassessment of patient selection criteria and care should be continually assessed through the pandemic and may change as capacity status changes and more is learned about the disease. • ecmo should only be considered in carefully selected covid- patients. (refer to patient selection section). ecmo should not be considered in patients who are unlikely to benefit and in those with significantly reduced life expectancy from preexisting disease. , • ecmo is a highly technical therapy and is resource intensive. although the distribution of this therapy should be as equitable as possible, during a pandemic such as covid- , distribution should focus on optimal candidates for recovery. • we recommend involvement of supportive and palliative care teams, before cannulation and throughout the ecmo course, in situations where centers are running at contingency or crisis capacity. virtual meetings with use of videoconferencing tools to limit need for exposure to covid- may be beneficial. • futility is a decision made at the bedside by the treatment team on a case-by-case basis. definitions of futility may change as we learn more about the trajectory of disease and recovery profiles in patients supported with ecmo. • ecmo should be discontinued if poor quality of survival is highly likely (severe neurologic insult, no heart or lung recovery with no possibility of a durable device implantation or transplant). • progressive multiple organ failure despite timely and optimal cardiopulmonary support indicates a poor prognosis, and we recommend that goals of care be reassessed and ecmo discontinued after discussion with family. • quality assurance and clinical governance frameworks must be maintained with ecmo quality reviews conducted frequently to measure overall outcomes, identify problems, and formulate plans for corrective actions. • we recommend that elso develop validated quality and process metrics specific to ecmo use during pandemics. • collection and sharing of data is important to ensure preparedness and patient care, especially in parts of the world yet to be affected. • the elso registry should continue to serve as useful resource during a pandemic and provide valuable real-time data to track global ecmo activity and to provide preliminary guidance on patient selection and outcomes. elso member centers are encouraged to enter minimum data prospectively at the initiation of the ecmo so that valuable real-time preliminary guidance may be obtained from the elso registry. • centers that are providing ecmo and are not elso members are encouraged to join elso and enter covid- cases into the registry. membership fee is waived during this pandemic. • understandably, ecmo centers are likely to face an increase in research participation requests during the pandemic. we recommend that elso and global ecmo research networks such as the international ecmo network develop a system of expedited endorsement of clinical studies during the pandemic. this is important to ensure that ecmo centers prioritize participation in global data collection, clinical trials, elso registry-based studies or other clinical studies that are most likely to yield meaningful results to guide ecmo practice. • we recommend ecmo centers participate in the elso and the ecmonet endorsed ecmocard study coordinated by the asia-pacific elso and the euroelso ecmo survey. • we recommend that elso develop a pandemic research plan with ready-to-go research proposals and preapproved ethics in place so that evidence-based guidance is generated in the quickest possible time to benefit most patients. adhere to local or institutional policies on ppe use for covid- patients ecmo initiation, and decannulation and bedside care should be performed with appropriate airborne plus contact precaution ppe including n /ffp mask, gown, cap, eye protection (e.g., goggles or visor) ecmo initiation, decannulation, and all agps be performed with ppe and n masks or papr with full contact precautions although caring for covid- ecmo patients wear appropriate ppe including n /ffp masks, gowns, cap, eye protectors (e.g., goggles, visor) and follow contact precautions for procedures in which splashing or aerosol generation is anticipated, a higher level of protection (e.g., gown at aami level or equivalent) should be considered labor-intensive procedures (e.g., mobilization, prone positioning, transport) carry significant risk of infection control breach to staff. we recommend that careful planning and team briefing be conducted beforehand while keeping the number of staff performing the procedure to the minimum simulation training on management of ecmo emergencies (e.g., cardiac arrest, pump failure) while wearing ppe or papr, since infection control breaches are more likely to occur in a stressful environment, should be scheduled. additionally, performing procedures in full ppe should also be considered in the event of ppe shortage adhere to the local hospital policies use papr after appropriate training extending the use of n /ffp masks could also be considered aami, association for the advancement of medical instrumentation; agp, aerosol generating procedure; covid- , coronavirus disease ; ecmo, extracorporeal membrane 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guidelines_and_clinical_resources/nutrition% therapy % covid- _sccm-aspen.pdf hydroxychloroquine and azithromycin as a treatment of covid- : results of an openlabel non-randomized clinical trial a trial of lopinavir-ritonavir in adults hospitalized with severe covid- using pk/pd to optimize antibiotic dosing for critically ill patients antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease pneumonia in wuhan, china saudi critical care trial group: corticosteroid therapy for critically ill patients with middle east respiratory syndrome extracorporeal membrane oxygenation and cytokine adsorption early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study cannula and circuit management in peripheral extracorporeal membrane oxygenation: an international survey of countries how i wean patients from veno-venous extra-corporeal membrane oxygenation weaning from veno-venous extracorporeal membrane oxygenation: how i do it predictors of successful extracorporeal membrane oxygenation (ecmo) weaning after assistance for refractory cardiogenic shock safe patient transport for covid- incidence of complications in intrahospital transport of critically ill patients-experience in an austrian university hospital improving the use of personal protective equipment: applying lessons learned available at: www.elso.org/portals/ /elsoguidelinesneonatal respiratoryfailurev _ _ initiation of a new infection control system for the covid- outbreak available at: unesdoc.unesco.org/ark:/ /pf available at: internationalecmonetwork.org we would like to thank dr. robert bartlett and dr. michael mcmullen from the executive committee for their invaluable comments for the guideline. our immense gratitude goes to the extracorporeal life support organization (elso) staff elaine cooley, peter rycus, and christine stead, who have worked tirelessly through these trying times to help get the guideline published on time. key: cord- -fh tj qr authors: lim, jae hong; kwak, jae gun; min, jooncheol; kwon, hye won; song, mi kyung; kim, gi beom; bae, eun jung; kim, woong-han; lee, jeong ryul title: experience with temporary centrifugal pump bi-ventricular assist device for pediatric acute heart failure: comparison with ecmo date: - - journal: pediatr cardiol doi: . /s - - - sha: doc_id: cord_uid: fh tj qr though ventricular assist devices (vads) are an important treatment option for acute heart failure, an extracorporeal membrane oxygenator (ecmo) is usually used in pediatric patients for several reasons. however, a temporary centrifugal pump-based bi-vad might have clinical advantages versus ecmo or implantable vads. from january to july , we retrospectively reviewed pediatric patients who required mechanical circulatory support (mcs) for acute heart failure. cases with postoperative mcs were excluded. since , we have tried to immediately add a right vad rather than ecmo, when the patients begin to present features of right heart failure after left vad support started in cases that the patients’ respiratory function did not require an oxygenator. original diagnoses included dilated cardiomyopathy (n = ), myocarditis (n = ), and others (n = ). eleven patients were supported by bi-vad, and patients were supported by ecmo; of these. four patients were successfully weaned from vad, and patients were weaned from ecmo. eleven patients underwent heart transplantation. overall, we have ( . %) early mortalities. there were no significant differences in early mortality, morbidity, and weaning rate between the bi-vad group and the ecmo group. during the support, patients with bi-vads significantly required fewer platelets and showed less hemolysis than ecmo patients. patients with myocarditis were successfully weaned from bi-vad support and bridged to transplantation thereafter. a temporary centrifugal pump-based bi-vad was clinically comparable to ecmo for pediatric patients with acceptable pulmonary function. mechanical circulatory support (mcs) has become an important treatment option for patients with acute decompensated heart failure that is refractory to other medical therapies [ ] . many studies reported various results of mcs including extracorporeal membrane oxygenation (ecmo) and ventricular assist device (vad) [ ] [ ] [ ] [ ] [ ] . some authors have reported that vad confers a statistically significant increase in survival after heart transplantation over ecmo for children with end-stage heart failure [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . however, most of these studies have focused on implantable vads. there are limitations to the use of vads in pediatric patients due to their diminutive sizes, especially in cases requiring bi-ventricular support. therefore, historically ecmo has been the traditional course of action for pediatric patients regardless of their respiratory function. a variety of implantable vads are available worldwide, however, the temporary centrifugal pump vad system is still used in this topic was presented in poster session in th "the society of thoracic surgeons" annual meeting in san diego, ca, january , -january , . selected cases or specific situations, for examples, in a case that patient's heart failure is anticipated to be recovered fast with just a short-term mechanical support, or in a situation that a sufficient financial support for durable vad by private of national insurance system is not available. in korea, implantable vads were not available before . however, even though "korean ministry of food and drug safety" approved to use implantable vads, we still have many restrictions to apply an implantable vad because of highly appropriated medical expenses to use with limited indications for being supported by a national insurance system. the use of biventricular assist devices (bi-vads) has been associated with decreased survival rates in many studies [ , , , ] . in these studies, the addition of right vad (rvad) support in patients already supported by left vad (lvad) was in response to disease progression, i.e., right ventricular (rv) failure and, as such, was linked to poor patient outcome. however, given this selective application, it remains unclear whether bi-vad themselves are a risk factor. in fact, the implantation of a rvad prior to rv failure could contribute to better patient outcomes for those with belated rvad deployment or receiving ecmo support, even in small pediatric patients. therefore, the goal of this study was to examine the clinical outcomes after bi-vad and ecmo-based interventions for medically intractable acute decompensated heart failure in a young patient population. we enrolled patients from january to july who were assisted by mcs for medically intractable acute decompensated heart failure. baseline and follow-up data were collected from the patients' medical chart. this study was approved by the seoul national university hospital institutional review board (irb) with waived patient consent (irb number: c- - - ). all procedures were performed in accordance with the principles outlines in the declaration of helsinki. we excluded postoperative patients with mcs. all of the patients received temporary centrifugal pump-based bi-vads assembled with bio pump (medtronic, inc., minneapolis, mn, usa) and rotaflow (maquet, jostra medizintechnik ag, hirrlingen, germany). all of the patients in the bi-vad group were centrally cannulated under median sternotomy. drainage and perfusion catheters were usually cannulated at the left atrium through the right upper pulmonary vein and ascending aorta for the lvad, and the right atrium and main pulmonary artery for the rvad. ecmo (veno-arterial only) patients were cannulated either centrally or peripherally (neck or groin vessels) depending on the patient's body weight or situations that patients encountered, for example, emergent status or not, the patient's cardiac operation (chest open) history. peripheral vascular accessibility was determined by ultrasonography prior to the procedure. if the left ventricle (lv) was not decompressed efficiently, then we placed an additional cannula in left atrium and ventricle through right upper pulmonary vein or left atrial appendage. we divided the patients into two cohorts, the bi-vad group and ecmo group, according to which device the patients were supported with initially. outcome data were compared and analyzed for statistical significance. we also looked at patient outcomes over time (before and after ). since , of ( . %) patients, we have tried to add a rvad rapidly and immediately for the patients who were already being supported by a lvad if the patients began to show the features of rv failure. before , conversion from ecmo to vads or early rvad application was not considered or performed as actively as after . we also immediately changed from ecmo to bi-vad-based support for patients whose pulmonary function recovered after initial ecmo intervention. chest x-ray and arterial blood gas analysis (abga) were the primary evaluation tools used to assess pulmonary function. if the patient presented a clear lung field on their chest x-ray, a partial pressure of o over mmhg, and less than mmhg of co on the abga with a - % of fraction of inspired o (fio ), we applied rvad rather than ecmo for rv failure. we opted for a rvad in patients who had just begun to present clinical symptoms of rv failure (e.g., ascites, pleural effusions, renal or hepatic dysfunction, progression of tricuspid regurgitation, or frequent ventricular arrhythmias) rather than increasing medical treatment efforts (e.g., increasing dosage of milrinone [more than . mcg/kg/min] or nitric oxide gas [more than mmhg] or adding additional pharmaceutical agents). for patients already supported by ecmo due to accompanied respiratory problems or easy access through peripheral vessels in an emergency situation, we sought to switch to bi-vad as soon as the patients' pulmonary function improved from its initial deteriorated state or was considered tolerable and no longer required the support of an oxygenator. in the operating room, after lvad insertion, we monitored rv function using transesophageal echocardiography (change in tricuspid valve regurgitation amount, rv contraction and regional wall motion, and pulmonary hypertension), and central venous pressure. if rv function began to deteriorate, we insufflated nitric oxide gas and infused intravenous milrinone; however, when rv function did not improve despite these efforts, we did not hesitate to apply the rvad for patients with acceptable lung function. these decisions were reached by a multidisciplinary team of cardiologists, cardiac surgeons and anesthesiologists. after mcs, all of the patients received anticoagulation therapy using intravenous heparin without other oral agents, such as warfarin or antiplatelet agents. the target for ecmo was to s for the activated prothrombin time (aptt) and the activated clotting time (act) target was to s. for vad, the aptt target is to s (act of to s). we checked the aptt every h and act once daily. heparin infusion was temporarily suspended in patients with bleeding tendencies until these improved. the circuit of the mcs was checked every h to detect thrombus formation in the line by nursing staffs, and if we had thrombi in the circuit, we increased the dosage of heparin slowly even though the lab findings were in tolerable range. when the amounts of thrombi increased despite increasing heparin, we considered changing of the circuit. recently, we try to keep a patient's consciousness to be awake and to provide an enteral feeding unless a patient complains severe pain. we consult a bed-side physical rehabilitation therapy to the department of rehabilitation to prevent possible musculoskeletal problems caused by a long-term bed-ridden status. we enlisted patients for transplantation; eight patients in the bi-vad group and twelve patients in the ecmo group. all data were analyzed using the spss software for windows (spss, chicago, il, usa), and p < . was considered statistically significant. continuous data are expressed as a mean ± standard deviation or median with range and compared by student's t test or the mann-whitney u test. the categorical variables were subject to univariate analysis using the chi-squared test or fisher's exact test for categorical variables. the multivariate analysis was based on logistic regression. the survival was estimated using the kaplan-meier method and defined as the time elapsed from mcs date to death or last follow-up. the preoperative patient characteristics are shown in table . the median age of patients with mcs was . years (range: . - . years) in the bi-vad group (n = ) and . years (range: - . years) in the ecmo group (n = ). among eleven patients in the bi-vad group, five were supported by a bi-vad initially and then maintained until weaning or transplantation. another five were initially supported by ecmo that was eventually converted to bi-vad after median . days (iqr: . - . days) of ecmo support, and the other one was supported by ecmo initially, and then converted with lvad after pulmonary function was restored, however, eventually rvad was added. in the ecmo group, there was no case that was supported by bi-vad initially and then was converted to ecmo support in the end. we added a rvad days and days after prior lvad support, respectively, in cases. the median body weight was . kg (range: . - . kg). diagnoses included dilated cardiomyopathy (dcmp, n = , %), myocarditis (n = , . %), and others (n = , . %); two cases of cardiomyopathy from autoimmune origin and stress-induced by chemotherapy, two cases of acutely progressive cardiac dysfunction by congenital valvular diseases (tricuspid regurgitation and mitral regurgitation), case of acute biventricular dysfunction accompanying with persistent pulmonary artery hypertension, case of acutely aggravated right heart failure with pulmonary edema accompanying with viral pneumonia and significant pulmonary vein stenosis that had been progressed after repair of total anomalous pulmonary venous return for several months, and case of acute right heart dysfunction accompanying with tricuspid regurgitation and borderline left ventricular dysfunction that we failed to find out specific reasons for this patient's cardiac dysfunction. renal impairment was found preoperatively in subjects from the bi-vad group and from the ecmo group (p = . ). preoperative hepatic impairment was present in patients from the bi-vad group and from the ecmo group (p = . ). clinical features before mcs are shown in table . three patients in the bi-vad group and patients in the ecmo group were supported by a mechanical ventilator before the operation (p = . ). there were no differences in metabolic acidosis, pao , paco , bicarbonate, and base excess between the two groups. table shows the clinical outcomes of the two groups. we were able to support patients longer with bi-vad (median days, iqr: - days) than with ecmo (median days iqr: - days), even though this difference did not reach statistical significance (p = . ). in-hospital mortality was seen in patients ( . %) from the bi-vad group and ( . %) from the ecmo group (p = . ). patients with bi-vad support had similar rates of mcs rate and successful transplantation after mcs ( . %) with patients with ecmo support ( . %). figure shows comparison of overall numbers of the patients who underwent transplantation (including mortality cases, in bi-vad group, in ecmo group), who expired, and survived after mcs, from bi-vad group (blue) and ecmo group (orange). the total transfusion amount, which was adjusted by body surface area, also did not differ between the two groups. however, the amounts of platelets transfused was significantly different between the two groups; median: . ml/m /day, iqr: . - . ml/m /day in bi-vad group; median: . ml/m /day, iqr: . - . ml/m /day in ecmo group, p = . , table ). the hemolysis, that is considered as a positive finding when indirect bilirubin, plasma hemoglobin, or ldh increased, rate was lower in the bi-vad group compared with the ecmo group (p = . , table ). the nadir pao was significantly lower in the ecmo group than the bi-vad group during the mcs despite the use of an oxygenator ( table ). the kaplan-meier analysis indicated there was no overall survival difference between the two groups during median . months of follow-up (iqr: . - . months) (fig. a) . mortality was occurred median . days (iqr: . - . days) after mcs was started in bi-vad group, and median . days (iqr: . - . days) after mcs started in ecmo group. several parameters were compared and analyzed between the two groups, patients who had successfully weaned from mcs and patients who failed to wean from mcs or heart transplantation ( table ). the patients with dcmp (p = . ) and heart failure before mcs (p = . ) had a lower rate of successful weaning. peak creatinine (p = . ) and bun (p < . ) levels were also significantly different between the successfully weaned and failure to wean groups. the multivariable analysis when we considered "heart transplantation after mcs support" and "successful weaning" as an "eventual successful mcs", although the numbers did not reach statistical significance, we had a greater proportion of patients with myocarditis successfully weaned from mcs or successfully underwent transplantation after mcs ( of , . %). regarding dilated cardiomyopathy, though we have small numbers of patients who were supported by bi-vad initially, we have more patients who were supported by bi-vad from the beginning of the mechanical support in the successful intervention group ( . %) than the failed intervention group ( . %). there were cases of mcs before and after . figure shows the case numbers of mcs after . after , complication rate of mcs was significantly decreased (p = . ). bleeding complications were particularly lower than before (p = . ). the early morality rate tended to improve after , but it did not reach statistical significance (p = . ). analyses of outcomes by era are shown in table . this study investigated differences between the clinical outcomes of temporary centrifugal pump-based bi-vad and ecmo as rescue treatments for medically intractable acute decompensated heart failure in pediatric patients. traditionally, to support small pediatric patients with medically intractable heart failure, ecmo is preferred over a vadbased system even when the patients have no respiratory issues and do not require an oxygenator; the limitations that underlie this treatment choice are largely associated with the challenges of applying vad systems to small patients. for example, vads require a central approach via sternotomy and this can induce more bleeding complications than the peripheral approach frequently used for ecmo insertion. for the bi-vad specifically, the operative field is particularly complicated, especially in small patients, as at least four cannulae are required. however, in , we started favoring a centrifugal pump-based vad over ecmo for its longevity and to avoid the complications associated with ecmo, in cases that do not require immediate peripheral vessel approaches. even though the ecmo was applied initially, after the patient's respiratory function recovered and no longer required oxygenator support, we tried to change the ecmo to a vad as soon as possible. this approach was also applied in cases of pediatric patients' rv dysfunction appearing or progressing after lvad insertion despite nitric oxide gas or milrinone treatment. if the patient's lung condition allowed, we added a rvad rather than an ecmo for rv support. implantable vads have only been approved for use in pediatric patients in korea since , and the medical insurance system still does not provide sufficient financial support for the patient's family. therefore, implantable vad is still not a straightforward option in korea. given this situation, applying a temporary vad using centrifugal pumps has some financial advantages than immediately applying the implantable is more durable than ecmo-based system because we generally maintain the mcs in the presence of low levels of anticoagulants in the vad-based system, which results in less hemorrhagic, fewer hemolytic complications and smaller transfusion volumes. previous studies reported that the bi-vad represents a significant risk factor for poor outcomes [ , , ] because adding a rvad after lvad insertion means that the patients' right heart is unable to endure the preload produced by the mechanically-assisted left heart, even with ample pharmaceutical support for right heart. for the present study, we chose a different approach that involved applying the rvad earlier than previous studies described. when a patient with no major respiration issues began to present with rv dysfunction despite continued medical treatment, we chose to add the rvad rather than adding more medicine. given that the aggravation of rv dysfunction after lvad support over time is not uncommon [ ] [ ] [ ] , some authors have emphasized the importance of appropriately timing unloading both ventricles for successfully bridging to recovery [ , ] . we expected that our early bi-vad application strategy would lead to better outcomes in terms of successfully bridging to recovery or transplantation, with lower complication and mortality rates than ecmo-treated patients; however, there were no significant differences in the mortality rate and weaning rates between the bi-vad and ecmo groups in this study. this might be due to the small number of patients for whom this strategy was applied since our early rvadapply strategy has only been used for to years. repeating this analysis in the future on a larger patient cohort should provide more statistically meaningful information regard the effect of our strategy on patient outcomes, because, in terms of hemolysis and cryoprecipitate transfusion amounts, the bi-vad group required significantly less than the ecmo group, despite the small sample size. we also found that rates of early mortality, bleeding complications, and rbc, ffp transfusion amounts tended to improve by time ( [ ] . in our study, patients with hepatic and renal dysfunction that progressed during the mcs had lower rates of weaning compared with patients without these complications; however, preoperative hepatic and renal dysfunction were not risk factors for bi-vad-based intervention. this could be due, in part at least, to our approach of implanting the rvad earlier than previous studies, namely, before hepatic or renal function became aggravated; however, it could also be that earlier application of the rvad, or bi-vad support, might prevent the development of renal or hepatic dysfunction, and this could lead to improved weaning rates or successfully bridging to next treatment stage, (i.e., heart transplantation). implantable vad systems are an effective treatment for heart failure. this study showed that a temporary centrifugal pump-based bi-vad remains relevant in selected cases of medically intractable acute decompensated heart failure, particularly in patients with myocarditis with acceptable pulmonary function. it enables effective biventricular unloading for myocardial recovery while buying additional time to determine the best-suited treatment option (i.e., an implantable vad system or transplantation) and is relatively cost-effective. especially when treating myocarditis, it represents an affordable option for recovery before considering the implantable vad system as the recovery period of this particular disease is shorter than most other causes of heart failure. this retrospective, non-randomized, single-center study has several limitations. the small size of the sample population prevented high power statistical analyses and restricted the interpretation of the results. regardless, we were nonetheless able to establish that the rapid application of a temporary centrifugal pump-based bi-vad was not clinically inferior to the traditional ecmo-based treatment regimen in terms of pediatric patients. furthermore, our findings illuminated some benefits and advantages including the decreased hemolysis and transfusion required with the bi-vad approach. based on these results, we will continue to employ our strategy of early rvad addition for patients already supported by lvad with acceptable levels of respiratory function when the patient initially shows signs of rv deterioration instead of increasing medical treatment efforts up to its' maximal level. conflicts of interest none. improved survival in patients with ventricular assist device therapy: the university of wisconsin experience pediatric heart failure: current state and future possibilities venoarterial extracorporeal membrane oxygenation for treatment of cardiogenic shock: clinical experiences in adult patients ventricular assist devices in pediatrics early biventricular assist device use in children: a single-center review of patients berlin heart study i ( ) prospective trial of a pediatric ventricular assist device excor pediatric ventricular assist device for bridge to heart transplantation in us children a longer waiting game: bridging children to heart transplant with the berlin heart excor device: the united kingdom experience bridging children of all sizes to cardiac transplantation: the initial multicenter north american experience with the berlin heart excor ventricular assist device pediatric heart transplant study i ( ) outcomes of children bridged to heart transplantation with ventricular assist devices: a multi-institutional study interagency registry for mechanically assisted circulatory support (intermacs)-defined morbidity and mortality associated with pediatric ventricular assist device support at a single us center: the stanford experience outcomes with ventricular assist device versus extracorporeal membrane oxygenation as a bridge to pediatric heart transplantation right ventricular dysfunction in children supported with pulsatile ventricular assist devices preliminary single center north american experience with the berlin heart pediatric excor device diagnosis, medical treatment, and stepwise mechanical circulatory support for fulminat myocarditis the achilles' heel of left ventricular assist device therapy: right ventricle outcomes of contemporary mechanical circulatory support device configurations in patients with severe biventricular failure key: cord- - ea vvsz authors: chu, yanan; li, tong; fang, qiang; wang, xingxiang title: clinical characteristics and imaging manifestations of the novel coronavirus disease (covid- ): a multi-center study in wenzhou city, zhejiang, china date: - - journal: j infect doi: . /j.jinf. . . sha: doc_id: cord_uid: ea vvsz nan we read with great interest the article by wenjie yang and colleagues , accepted for publication in the journal of infection. the authors performed a retrospective multi-center cohort study and presented important data regarding the observation that most patients of novel coronavirus disease (covid- ) from wenzhou city, zhejiang, exhibited mild infection. however, the information of critically ill patients, especially with icu care and extracorporeal membrane oxygenation (ecmo) treatment, were scare. no study to date has provided evidence that the clinical features of critically ill patients with confirmed covid- from zhejiang province. we performed a single-centered, retrospective, observational study to investigate the clinical characteristics and ventilation conditions of critically ill patients infected with sars-cov- . from late january, , to february , , critically ill patients in the icu of the first affiliated hospital of zhejiang university who were diagnosed as covid- in accordance with the diagnosis and treatment guidance published by the chinese government were enrolled in the study . we obtained patients demographics, epidemiology data, and details of laboratory tests, treatments, and ecmo implantation. the baseline epidemiological characteristics and clinical features of studied patients as classified by with or without ecmo treatment, were shown in table . most of the patients admitted to the icu were older and had several common comorbid conditions, which demonstrated that age and comorbidities might be the indicators for severely ill one and poor prognosis. of all patients, the mean age was . ± . years, and most of the patients were aged years and older. of the seven patients who received ecmo, the mean age was . ± . years. observed man probably had more complicated clinical conditions and worse inhospital outcomes as compared to women in severe covid- patients. the median time from onset of symptoms to hospital admission was days (iqr - days) which was longer than wenjie yang and colleagues' study. in terms of baseline laboratory data of severely confirmed covid- patients, three ( %) and ( . %) of patients exhibited leucopenia and lymphopenia, respectively. platelets levels on admission were lower in patients with ecmo treatment than non-ecmo patients. also, a recent case report verified the counts of peripheral cd and cd t cells were both decreased in a -year-old man with sars-cov- infection through the technology of flow cytometric analysis . specifically, the levels of aspartate aminotransferase (ast) and alanine aminotransferase (alt) on admission were higher in ecmo treated patients (median ast . table ). besides, admission levels of total bilirubin were increased substantially in ecmo treated patients. these abnormalities suggested that sars-cov- might be related to hepatic injury. however, almost all of the included patients received antivirus treatment, the drug induced liver injury could not be excluded. huang et al. reported that increased level of ast was found in about % of the icu patients in their study . therefore, damaged liver function is more common in serious covid- patients. up to now, there was no sufficient evidence to clarify sars-cov- as the main reason of damaged liver function. further studies should concentrate on the reasons of liver function damage in patients with covid- . the level of procalcitonin increased in more than % of included patients, and most of patients in our study received antibacterial and antifungal agents. one possible explanation for the results may be that many of the critically ill patients were associated with combined infection of bacterial or fungal before the commencement of ecmo. ecmo has been increasingly being used as a rescue treatment for refractory hypoxemia in patients with severe acute respiratory distress syndrome . the initial mode was veno-venous (vv) ecmo in the patients. initiation of ecmo was accompanied by a significant improvement in pao /fio ratio, and a significant decreases in paco , fio (table ). research showed too high level of fio was related to increased production of reactive oxygen-derived free radicals which are noxious to the humans health . in summary, our data indicate that sars-cov- infection might cause damage to the immune and liver function of covid- patients. ecmo support was associated with improved ventilation conditions in covid- patients with refractory hypoxemia. the study may be helpful to providing evidence of the appropriate time to initiate ecmo for critically ill patients with covid- , and add further evidence for critically ill patients characteristics by wenjie yang et al. clinical characteristics and imaging manifestations of the novel coronavirus disease (covid- ):a multi-center study in wenzhou city national administration of traditional chinese medicine. guidelines for the diagnosis and treatment of novel coronavirus pneumonia (trial version sixth) pathological findings of covid- associated with acute respiratory distress syndrome clinical features of patients infected with efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial bench-to-bedside review: the effects of hyperoxia during critical illness the authors would like to thank all participants of the study , the nurses and clinical staff who are providing care for the patients, and thanked for the guidance and help from hdh, wyk. this work was supported by the department of science and technology of zhejiang province. the authors of this study declared no conflict of interest. key: cord- - be d authors: nan title: abstracts der . gemeinsamen jahrestagung der dgiin und Ögiain. der mensch – ein anspruchsvoller arbeitsplatz. .- . juni in berlin, estrel berlin date: - - journal: med klin intensivmed notfmed doi: . /s - - - sha: doc_id: cord_uid: be d nan the slope-intercept of lactate increase over the observational period was significantly higher in patients with citrate accumulation (+ . mmol/l/h vs. − . mmol/l/h, p < . ). in the group of patients with initially severe lactatemia (> = mmol/l) the calculated lactate clearance at h, h and h was at each time-point significantly higher in the non-accumulation group (median . %, . % and . %) , than in patients with citrate accumulation (median − . %, − . % and . %, respectively; p < . ). among the serum lactate clearance at , or hours the highest roc-auc values for citrate accumulation were observed for h lactate clearance (auc = . ; % ci . - . ) with the best cut-off value of . %. conclusion: risk of citrate accumulation during rca-crrt even in patients with initially severe hyperlactatemia remains low. lactate kinetics over time rather than initial lactate levels is a predictor of citrate accumulation. ander folgenden tagen wurden plasmaproben (n = ) entnommen und die meropenem-konzentrationen mittels hplc-uv gemessen. die anschließende populations-pharmakokinetische analyse erfolgte mittels des nonparametric adaptive grid (npag) algorithmus in pmetrics®. es wurden monte carlo simulationen für die ersten h und für eine h sled sitzung durchgeführt. hiermit wurde das fraktionierte target attainment (fta) gegen die mhk verteilung von p. aeruginosa isolaten mit einem pharmakodynamischen ziel von und % f t > mhk berechnet. ergebnisse: ein zwei-kompartiment-model erwies sich zur beschreibung der population als am besten geeignet. die restdiurese (rd) wurde als variable für die verbleibende meropenem-clearance (cl) in das finale model aufgenommen und führte zu einer signifikanten verbesserung der goodness-of-fit plots. die mittlere meropenem cl unter sled sowie das zentrale verteilungsvolumen betrugen im mittel , l/h (std.abw.: , ) und , l/kgkg ( , ). sofa score, alter und gewicht lagen im median bei [ ] [ ] [ ] [ ] [ ] , jahren und kg [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . die mittlere restdiurese (rd) und die zeit unter sled betrugen ml/d ( . ) und min ( . ). eine dosis von mg alle h und eine rd von ml/d erzielten eine fta von % für das konventionelle target von % f t > mhk. ausgehend von einem target von % f t > mhk werden nur % der sensiblen p. aeruginosa stämme abgedeckt. zusammenfassung: die studie zeigt eine hohe inter-und intra-individuelle pharmakokinetische variabilität im kollektiv. auch die restdiurese hat einen deutlichen einfluss auf die cl von meropenem. daher erscheint ein therapeutisches drug monitoring weiterhin essentiell, um die behandlung der patienten, insbesondere bei intermediär sensiblen keimen optimal zu kontrollieren und zu steuern. hyperlactatemia as a predictor for citrate accumulation in critically ill patients undergoing cvvhd with regional citrate anticoagulation d. khadzhynov; o. staeck; a. dahlinger ; f. halleck; h. peters ; k. budde; t. slowinski medizinische klinik mit schwerpunkt nephrologie, innere medizin mit schwerpunkt nephrologie, campus charité mitte, charité -universitätsmedizin berlin, berlin; objective: regional citrate anticoagulation (rca) for continuous renal replacement therapy (crrt) is widely used on intensive care units (icus) . systemic citrate accumulation is a complication of rca-crrt. the objective of the present study was to investigate the predictive capability of lactate concentrations and time-dependent lactate kinetic regarding citrate accumulation and to describe the feasibility of rca-crrt in patients with severe lactatemia. method: retrospective, observational study at a university hospital with icus. all patients treated with rca-crrt during the -year study period were screened for signs of citrate accumulation. results: among patients treated with rca-crrt overall incidence of citrate accumulation during the first hour of therapy was . %. regarding lactate concentrations at time of initiation of rca-crrt, incidence of citrate accumulation was . % and . % among patients with elevated lactate concentration (> . mmol/l) and severe hyperlactatemia (≥ mmol/l), respectively and . % in patients with normal lactate concentration. initial lactate concentration showed a receiver-operating-characteristics area under the curve (roc-auc) of . for prediction of citrate accumulation. however, the optimal cut-off calculated from roc ( . mmol/l) had strong negative predictive value of . % ( % ci . - . %), whereas positive predictive value was only . % ( % ci . - . %). verfolgt das ziel, in den gesamten prozessabläufen der ina für diese zielgruppen intelligente assistenzdienste zur bedarfsorientierten "in situ" unterstützung in der notfallversorgung web-basiert zur verfügung zu stellen. methode: mit hilfe strukturierter fragebögen und experteninterviews wurde zunächst eine bedarfsanalyse in bezug auf prozesse, rollen und dienste in der notfallversorgung der ina durchgeführt. in kooperation mit den zuständigen fachgesellschaften wurden informationen zu vorhandenen qualifizierungsmaßnahmen ermittelt. nachfolgend wurden die lehr-/lerninhalte festgelegt und exemplarisch einsatzszenarien definiert. technologisch erfolgten eine digitalisierung definierter lehr-lerninhalte sowie die entwicklung von systemdiensten für eine intelligent-adaptive lernumgebung. ergebnisse: in der ersten projektphase wurden die prozessabläufe in der präklinischen und klinischen phase der notfallmedizin detailliert analysiert, der jeweilige prozess-spezifische informationsbedarf für die zielgruppen ermittelt und in bpmn modelliert. die ergebnisse zur mediennutzung zeigen, dass die mehrheit der teilnehmer bereits mobile endgeräte nutzen und die informationstechnologie als nützliches hilfsmittel für schnelle und effektive informationsgewinnung ansehen. die analyse der qualifizierungsmaßnahmen ergab für den bereich der notfallpflege einen dringenden bedarf zur definition von lernzielen. nach erstellung eines benutzermodells wurden definierte lehr-/lerninhalte digitalisiert und erste assistenzdienste programmiert. zusammenfassung: mit hilfe einer detaillierten grundlagenanalyse wurde der bedarf an intelligenten unterstützungsdiensten in der ina für die stetige berufliche qualifizierung von rettungsdienst-und notfallpflegekräften ermittelt. auf basis etablierter techniken der künstlichen intelligenz sind nachfolgend erste assistenzdienste und systemdienste für ein intelligent-adaptives lernsystem entwickelt worden, die zeit-und ortsunabhängig eingesetzt werden können. j. frick; a. slagman; j. searle; m. möckel notfallmedizin/rettungsstellen nordcampi, campus virchow-klinikum und campus charité mitte, charité -universitätsmedizin berlin, berlin; hintergrund: das ziel ist die beschreibung der fallbezogenen prävalenz und mortalität von stationär aufgenommenen herzinsuffizienzpatienten c. reithmann; b. herkommer; m. fiek medizinische klinik , helios klinikum münchen west, münchen; hintergrund: der elektrische sturm (es) mit häufigen adäquaten icd schockabgaben stellt ein traumatisierendes ereignis mit hoher sterblichkeit dar. die dringlich oder notfallmäßig durchgeführte ablation ventrikulärer tachykardien (vt) ist die therapie der wahl mit nachgewiesener mortalitätssenkung. die bestmögliche interaktion zwischen prä-interventioneller intensivmedizin und vt ablation ist nicht etabliert. methode: konsekutive patienten ( m, w, ± jahre) mit häufigen icd interventionen oder es unterzogen sich insgesamt ablationsprozeduren. die patienten wurden vor der dringlichen oder notfallmäßigen vt ablation in der regel auf intensiv-oder imc station behandelt. als grunderkrankung bestand bei patienten eine ischämische kardiomyopathie (cmp), bei eine nichtischämische cmp, bei eine ar-vc/d, bei eine kardiale sarkoidose und bei keine nachweisbare herzerkrankung. folgende spezifische maßnahmen wurden in der regel auf intensivstation durchgeführt: . de-aktivierung der icd therapien oder umprogrammierung, um weitere icd schockabgaben zu vermeiden und zur vt dokumentation. . -kanal ekg dokumentation von spontan auftretenden vt oder ves als zielarrhythmie für die nachfolgende ablation. amiodaron, wenn klinisch vertretbar, um die induzierbarkeit der klinischen vt bei der ablation zu verbessern. . schmerzlose terminierung von spontan auftretenden vts mittels Überstimulation über das icd programmiergerät, durch transthorakale elektrokardioversion in kurznarkose oder durch antiarrhyth mika. ergebnisse: bei patienten ( %) wurden auf intensivstation spontane vt episoden dokumentiert und ohne automatische icd schocks terminiert. kein patient verstarb vor der elektrophysiologischen intervention. bei der ablation wurden bei patienten narben-abhängige reentry vts (vorherrschend lv: , rv: ), bei fokale non-reentry vts, bei vts bei purkinje disease und bei durch monomorphe ves induziertes kammerflimmern behandelt. bei patienten erfolgte eine epikardiale ablation und bei eine transkoronare alkoholablation. kein patient verstarb intraprozedural. im post-interventionellen in-hospital verlauf verstarben patienten ( , %) an einem therapierefraktären es (n = ) oder dekompensierter herzinsuffizienz (n = ). zusammenfassung: abgestimmte therapie-und monitoring-strategien auf der intensivstation können zur verbesserung der erfolgschancen der katheterablation bei elektrischem sturm beitragen. min) noch , % bzw. , % und sank nach weiteren fünf stunden o -therapie auf , % bzw. , % ab. die inhalative sauerstofftherapie wurde zur prophylaxe neurologischer spätschäden für insgesamt stunden fortgeführt. beide patienten konnten am folgetag ohne neurologische auffälligkeiten oder laborchemischen bzw. elektrokardiographischen hinweis auf eine kardiale beteiligung in beschwerdefreiem zustand nach hause entlassen werden. zusammenfassung: angesichts ihres multiplen, unter umständen sehr unspezifischen erscheinungsbildes stellt die co-vergiftung für den notfallmediziner vor allem bei fehlenden richtungsweisenden begleitumständen eine herausforderung dar, sollte jedoch zur einleitung einer adäquaten therapie, aber auch aus gründen des eigenschutzes für die helfer bei unklarer vigilanzminderung differentialdiagnostisch in betracht gezogen werden. a. kamp; n. paquet ; j. peter; f. trudzinski; c. metz; f. seiler; k. rentz; h. wilkens; r. bals; p. lepper pneumologie, allergologie, objective: following successful resuscitation from cardiac arrest (ca), neurological impairment and other types of organ dysfunction cause significant morbidity and mortality -a condition termed post-cardiac arrest syndrome. whole-body ischemia/reperfusion with oxygen debt activates immunologic and coagulation pathways increasing the risk of multiple organ failure and infection. we here examined the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (mif) in post-cardiac arrest syndrome. method: mif plasma levels of n = patients with return of spontaneous circulation (rosc) after ca were assessed with a previously validated method and compared to markers of systemic inflammation and cellular damage. icu patients without former ca and healthy volunteers served as controls. results: mif levels in patients after rosc were higher compared to those in healthy volunteers and icu patients without ca. kaplan-meyer analysis revealed a distinctly elevated mortality since day one that further increased towards an elevated -days-mortality in patients with high plasma mif. roc curve identified plasma mif as a predictor for mortality in patients after ca. correlation with inflammatory parameters revealed that high mif levels did not mirror post ca inflammatory syndrome, but distinctive cellular damage after rosc as there were strong correlations with markers of cellular damage like ldh and got/gpt. conclusion: high mif levels were associated with elevated -days-mortality and high mif predicted mortality after ca. we found a close relation between circulating mif levels and cellular damage, but not with an inflammatory syndrome. t. arnold; a. slagman; m. möckel notfallmedizin/rettungsstellen nordcampi, campus virchow-klinikum und campus charité mitte, charité -universitätsmedizin berlin, berlin; objective: cardiovascular disease is the main cause of death in germany. the new european society of cardiology (esc) guidelines recommend a rapid initiation of a dual antiplatelet therapy in acute coronary syndromes with acetylsalicylicacid and one of the new generation p y -inhibitors. aim of the study: to investigate whether the use of ticagrelor in comparison to other platelet-inhibitors is associated with a greater risk of bleeding or death in patients with acute myocardial infarction in the emergency room. method: in our retrospective multicenter trial we included all patients who were presentingto one of the three emergency departments of the charité berlin university hospitals in with the diagnosis of stemi or nstemi, corresponding to the icd-codes i . to i . . primary endpoints were the icd-codes d btw. t . as well as the need to transfuse blood products. secondary endpoint was in-hospital death of any cause. as combined endpoint we chose death and bleeding. results: overall bleeding rate was . % ( %-confidence interval (ci): . - . %). clopidogrel had a bleeding rate of . % ( % ci: . - . %), whereas it was . % ( %-ci: . - . %) for ticagrelor and . % ( %-ci: . - . %) for prasugrel with no statistical significant difference between the groups (p = . ). . % ( %-ci: . - . %) of all patients died, whereas it was higher for clopidogrel ( . % ( %-ci: . - . %)) than for ticagrelor ( . %; %-ci: . - . %) and for prasugrel ( . %; ( %-ki: . - . ; p = . ). . % ( %-ci: . - . %) in the clopidogrel-group reached the combined endpoint death and bleeding, for ticagrelor it was . % ( %-ci: . - . %) and % ( %-ci: . - . %) in the prasugrel-group without any statistical differences between the groups (p = . ). conclusion: patients with acute myocardial infarction and mostly acute interventional treatment have a high risk of bleeding compared to the published data. the new platelet inhibitors ticagrelor and prasugrel are safe substances in the acute treatment of myocardial infarction in the emergency room. the potential reduction in mortality in comparison to the older drug clopidogrel is facing the same bleeding risk on the other hand. our data support the actual guidelines in their favored use of prasugrel and ticagrelor. hintergrund: anamnese: eine jährige frau patientin mit langjähriger schizophrenie wird nach in suizidaler absicht erfolgter einnahme von mg risperidon ( tbl. á mg) mit laufender flüssigkeits-und noradrenalin (na)-therapie ( , µg/kg/min) komatös (gcs ) und extrem hypoton (rr / mmhg) durch den notarzt eingewiesen. initiale laborwerte: ph , , po , kpa (unter l o /min), pco , kpa, be - , hco ; k+ , ; na ; hb , ; kreatinin ; harnstoff , ; lactat , ; glucose (je mmol/l); leukozyten: (je gpt/l); methode: therapie in den ersten stunden: Übernahme auf die intensivstation, dort intubation, rasch sich entwickelnder exzessiver katecholaminbedarf mit kreislaufstillstand und reanimation. auch unter na-dosen von über , µg/kg/min lässt sich kaum ein mad > mmhg erzielen. deutlicher lactatanstieg bis , mmol/ l. ein probatorischer wechsel des katecholamins auf adrenalin als ultima ratio bleibt ohne effekt. ergebnisse: nach etwa stunden kann die zufuhr von na reduziert werden, die metabolische azidose ist rückläufig. unter na-dosis von , µg/ kg/min können jetzt arterielle mitteldrücke von mmhg erreicht werden. auch nach stunden sind jedoch noch na-dosen > µg/kg/min erforderlich. die extubation ist stunden nach der intoxikation möglich, die stellung, die vital-und laborwerte sowie die gewünschte fachdisziplin für die beschwerden dieser patienten und die zeitdifferenz zwischen aufnahmezeit und dem triagezeitpunkt und dem aufrufen durch den arzt bzw. dem zeitpunkt des verlassens der rettungsstelle. ergebnisse: es waren patienten, die vor arztkontakt die notaufnahme verließen. diese patientengruppe hatte überwiegend keine akut-behandlungsrelevanten vital-und laborwerte. es handelte sich eher um junge patienten (median - jahre) und die patienten waren häufig in einer niedrigen triagekategorie ( %). sie waren überwiegend deutscher staatsangehörigkeit ( %), wohnten hauptsächlich in berlin ( %), kamen vorwiegend selbständig zu fuß in die rettungsstelle ( %) und stellten sich vornehmlich freitags, samstags und montags (insgesamt % der patientengruppe) sowie tagsüber ( - uhr: % der patientengruppe) in der rettungsstelle vor, bevor sie diese vor arztkontakt wieder verließen. zusammenfassung: patienten, welche die rettungsstelle vor arztkontakt verließen sind charakterisiert durch eine überwiegend geringere behandlungsdringlichkeit ihrer beschwerden und es scheint sich nicht um akut-lebensbedrohlichen notfälle im klassischen sinne zu handeln. in einer aktuell laufenden folgestudie werden diese patienten in drei rettungsstellen der charité über einen längeren zeitraum erfasst und charakterisiert. c. thomas objective: we sought to investigate whether and to what extent similarities and differences in routinely collected hospital data exist between men and women presenting to a non-surgical ed. method: routinely available data of patients who attended one of two eds of the charité berlin within one year were retrieved from the hospital information system. patient's sex was assessed by the medical insurance card or obtained by patient interrogation. a descriptive data analysis was performed stratified by patient's sex in all patients and in subgroups with different leading symptoms: "chest pain", "dyspnea", "abdominal pain", "headache" and "none of these symptoms". results: within one year, , patients visited the participating eds, , women and , men. the majority of patients had no specific leading symptom at admission ( %). the leading symptom at admission differed significantly between men and women, with a higher proportion of men with chest pain ( % vs. %) and dyspnea ( % vs. %) and a higher proportion of women with abdominal pain ( % vs. %) and headache ( % vs. %; p < . ). patient characteristics and the association between the leading symptom at admission and underlying diagnosis were in general very similar in women and men. women were less frequently admitted for in-patient treatment ( . % women vs . % men; p < . ). this difference was significant in all symptom-groups (p < . for all) except headache (p = . ). women were also less frequently transferred to intensive care units (icu; . % vs. %; p < . ). this difference was again significant in all symptom-groups except headache. mortality in general was low in women and men ( . % vs. . %, p = . ) and did also not differ in symptom-based subgroups. conclusion: the use of secondary data is associated with limitations regarding data quality and completeness. in contrast to artificial study populations routine data reflect a real-life scenario as no in-or exclusion criteria are applied. despite the absence of major differences in the association between leading symptom at admission and underlying disease, women presenting to the ed receive less frequently inpatient-as well as icu-treatment. this difference does not lead to higher in-hospital mortality as compared to men in hintergrund: akute herzinsuffizienzsyndrome (ahfs) sind die häufigste ursache für hospitalisierungen in deutschland, verursachen enorme kosten und zeigen eine hohe mortalität. die prognose betroffener patient*innen lässt sich aktuell am ehesten aus der klinischen präsentation ableiten, was auch daran liegt, dass keine paraklinischen parameter verfügbar sind, die zuverlässig die mortalität der ahfs vorhersagen können. es gibt hinweise darauf, dass der il- -rezeptor soluble suppression of tumorigenicity (sst- ) ein hilfreicher biomarker für die risikostratifizierung sein könnte. methode: in der internistischen notaufnahme des campus virchow klinikums der charité wurden patient*innen mit akuter herzinsuffizienz (nyha iii-iv) im rahmen der birth-studie eingeschlossen. von der aufnahme bis zur entlassung wurden bis zu blutentnahmen (tag , , , , , entlassungstag) durchgeführt, aus denen sst- und bnp bestimmt wurden (st : presage® st ; critical diagnostics; san diego; prognostic cut-off: ng/ml; bnp: advia centaur; bayer healthcare; germany). primärer endpunkt war die -jahres mortalität durch kardiale ursachen. ergebnisse: daten von patient*innen mit akuter herzinsuffizienz mit vollständigen follow-up-informationen gingen in die analyse ein. die mediane sst- konzentration bei aufnahme lag bei , ( , - , ) (Überlebende) vs. , ( , - , ) (verstorbene), p = , . die roc-analyse ergab eine auroc von , ( , - , ) für bnp und , ( , - , ) für sst- , jeweils gemessen bei aufnahme bezogen auf die -jahres-mortalität. die kombination beider werte ergab eine auroc von our data indicate, that egc breakdown is mediated by angpt- , probably in a non-redundant manner. the results advance our understanding of the angpt/tie ligand-receptor system as a shared and concurrent gatekeeper of both layers of the vascular double barrier -the endothelial cell and the egc. given that tie axis drugs will be available in the future, therapeutic protection of the egc might become a feasible and important treatment goal to prevent vascular leakage in critical care nephrology. objective: angiopoietin- (angpt- ), an antagonist of the endothelium-stabilizing receptor tie secreted by endothelial cells, promotes vascular permeability. we have previously shown that administration of tie agonistic molecules, which counteract the devastating effects of angpt- , prevent ischemic and septic acute kidney injury, probably through endothelial-cell contraction and junctional disintegration. here we hypothesized that angpt- might mediate the breakdown of the endothelial glycocalyx (egc), a carbohydrate-rich vasoprotective layer lining the luminal surface of the endothelium, as well. method: confocal and atomic force microscopy were used to visualize and analyze the thickness of the egc on living endothelial cells. the miles assay, an in vivo permeability assay was used to quantify vascular permeability and edema formation in murine back skins. we show that exogenous angpt- induces a rapid loss of the egc in endothelial cells in vitro. glycocalyx deterioration involved the specific loss of its main constituent heparan sulfate paralleled by the secretion of the heparan sulfate-specific glucuronidase heparanase from late lysosomal stores. corresponding in vivo experiments revealed that exogenous angpt- leads to heparanase-dependent egc breakdown, which contributed to plasma leakage. objective: specific indication, timing, and clinical outcome of extracorporeal membrane oxygenation (ecmo) in patients with hematologic or oncologic disease are still under investigation. here, we report on the successful use of extracorporeal membrane oxygenation (ecmo) in a patient with mediastinal tumor mass compressing central airways. in an otherwise healthy -year old man suffered from thoracic pain and cough. ct scan revealed a large mediastinal mass with compression of the trachea, bronchial tubes and upper venous congestion, mediastinal shift, and massive pleural effusion. despite chest tube management ( ml serous exudate), respiratory situation worsened with intubation and mechanical ventilation needed. nevertheless, the patient developed progressive hypercapnia (paco mmhg) and respiratory acidosis (ph . ) caused by bronchoscopically confirmed slit-shaped airway compression. on admission to our quaternary center patient was ventilated using intermittent positive pressure (ippv) with . fio , cmh o peep and cmh o pmax. however, during the next hours even with maximum escalation of ventilator settings hypercapnia worsened. to stabilize respiratory situation we decided to implant va-ecmo as a bridging strategy. as the veins of the upper half of the body were compressed by tumor mass, femoral access was used for both, arterial and venous cannula. results: after respiratory stabilization, tumor biopsy was performed and revealed a t-cell lymphoblastic lymphoma. for initial debulking of the mediastinal mass emergency radiation and corticosteroids were used, leading to anatomic reconstitution of the upper airways, so ecmo could be explanted by day after admission. however, further course was aggravated by numerous complications and therefore final decannulation could not be done earlier than day . after multiple courses of systemic chemotherapy the patient received a final consolidation by allogeneic stem cell transplantation. after . years of long term follow up the patient showed a relapse free survival with % chimerism and without clinical signs of graft-vs-hostdisease. the present report demonstrates a clear benefit of temporary use of ecmo as a bridging strategy in patients suffering from a potentially reversible compression or obstruction of airways by malignant disease responding to anti-neoplastic treatment. objective: we present the case of a man who was admitted with a sudden onset of upper gastrointestinal bleeding after being treated for a bleeding esophageal ulcer. method: case presentation: a -year-old man presented with recurrent hematemesis to our hospital. he was managed in another hospital a few days earlier for the same reason, where endoscopic work-up revealed an esophageal ulcer, for which an over-the-scope clip (otsc) was applied. emergency endoscopy revealed the otsc in situ but no active bleeding. a hemoclip was applied over a vessel stump. the patient suffered from a hematemesis again three days later, when repeated endoscopy showed a spurting bleeding at the same site. a digital subtraction angiography did not show any active source of bleeding. re-assessment of the original ct scan led to the suspicion of an aorto-esophageal fistula due to a penetrating aortic ulcer (pau) at the site of the otsc placement. due to the massive bleeding, bridging to surgery seemed unfeasible, thus emergency angiography was performed to temporarily close the fistula. an aortic stent graft was inserted for definite treatment the following day. in the absence of mediastinitis and due to the good healing tendency of the ulcer, open surgical repair was avoided, considering the high mortality and post-surgical risk of infection. the patient recovered gradually and could be discharged home a month later. results: aorto-esophageal fistula is rare and it is associated with a high mortality. in our patient, the fistula was most likely due to pau at the site of the otsc application for an esophageal ulcer. either open surgical repair of the aorta and esophagus or endovascular stent grafting can be considered for fistula repair. in our case, the surgical option was considered risky. to date no data exist comparing both strategies regarding complications. the aorto-esophageal fistula in our patient may have been due to the otsc application. use of otsc for mid-esophageal ulcers should thus be critically evaluated due to the high risk of damaging neighboring structures. objective: a pheochromocytoma is a rare, mostly benign tumor of chromaffin cells in the adrenal medulla. it produces catecholamines that, once released, cause symptoms like episodic headache, hypertension, palpitations and augmented sweating. life-threatening events like acute cardiomyopathy, myocardial infarction or acute pulmonary edema and even multi-organ failure were described occasionally before. the gravity of complications seems to depend on the size of the pheochromocytoma and the blood level of catecholamines. results: we report the case of a -year old woman admitted to our institution with immense chest pain and dyspnea. shortly after arrival in our emergency department she developed a cardiogenic shock with a severe reduction of the left ventricular function. a pulmonary edema with respiratory insufficiency made an intubation necessary and inotropic agents were started. despite this treatment the patient became pulseless and was resuscitated for a couple of minutes. in order to stabilize the hemodynamic parameters a peripheral va-ecmo (cardiohelp, maquet®) was implanted via the femoral vessels. to prevent an aggravation of the pulmonary edema under va-ecmo therapy we decided to perform left ventricular decompression with an impella cp (abiomed® computer tomography of the whole body were passed. finally a × cm tumor in the left adrenal medulla was detected. the blood values presented extremely high levels of catecholamines. the synopses of all our examination results led us to the diagnosis of a pheochromocytoma. after medicinal alpha and beta-blockade the resection of the left adrenal medulla was performed. five days after the surgery the blood levels of catecholamines had normalized. one month after hospitalization the patient was discharged to a rehabilitation center. we are presenting in this case report, to the best of our knowledge, the first successful use of the combination of a peripheral va-ecmo with an impella cp to treat a patient with a cardiogenic shock and multi organ failure due to a pheochromocytoma. presence of a fragmented qrs complex, reduced glomerular filtration rate and lower blood pressure were more common in the ihca group compared to controls. conclusion: risk stratification of cardiologic in-patients based on routinely obtained parameters such as ecg and laboratory values seems practical and relatively easy. established early warning systems may therefore be adjusted for in-patients in cardiology in order to prevent sudden cardiac arrest. zusammenfassung: das pneumopericard kann also bettseitig sicher und schnell diagnostiziert werden. wegweisend ist dabei die auffällig schlechte beschallbarkeit (luftbedingt) und der nachweis des so genannten "gap signs", das einem pulssynchronen "comet-sign"-artefakt aus dem pericard entspricht. huvecs with tnfa (modelling the vascular response to sepsis in vitro) we found that significant tie shedding occurs in an mmp -dependant manner. an observation that we confirmed cross-species in mice and humans. however, given the dramatic reduction in tie transcription (− % in hrs) we further experimentally modelled a common feature of critical illnesses -i. e. hemodynamic shock -by investigating the effect of flow on tie transcription. we identified a novel pathway involving gata as a flow-dependent transcription factor regulating tie in sepsis. palliative häusliche versorgung mittels high-flow sauerstofftherapie eine dieser studien liefert eine gedvi-korrekturformel ( ). daher ist bei einem der kommerziell erhältlichen tptd-geräte (picco, pulsion medical systems se) die eingabe der venösen katheterposition nötig. es war ziel unserer studie, bei patienten mit venösem katheter sowohl in v korrekte eingabe der femoralen zvk-position) und den unkorrigierten gedvi-fem-unkor inkorrekte eingabe einer jugulären trotz femoraler zvk-position) mit dem goldstandard des gedvi-jug aus tptd über einen jugulären zvk zu vergleichen wilcoxon-test für verbundene stichproben, spss . ) ergebnisse: männliche, weibliche patienten; alter ± jahre, größe ± cm, gewicht ± kg. der gedvi-fem-unkor überschätzte den gedvi-jug ( ± vs. ± ml/m ; p < , ) erheblich. bias (+ ± ml/m ) und percentage error (pe: %) waren inakzeptabel. der gedvi-fem-kor unterschied sich zwar signifikant von gedvi-jug ( ± vs. ± ml/m ; p = , ), allerdings waren bias ( ± ml/m ) und pe ( %) klinisch akzeptabel. die korrektur wie in der o. g. studie ( ) vorgeschlagen lieferte ged-vi-fem-formel, der auch signifikant höher als gedvi-jug war ( ± vs. ± ml/m ; p = , ), allerdings einen noch geringfügig kleineren bias ( ± ml/m ) und pe ( %) als gedvi-fem-cor lieferte. gedvi-fem-cor und gedvi-fem-formel zusammenfassung: .) ein unkorrigierter gedvi aus femoraler tptd ist klinisch unbrauchbar. .) die in der letzten picco-software gebrauchte korrektur reduziert bias und pe erheblich und resultiert in klinisch akzeptabler genauigkeit und präzision. .) sie scheint der korrektur in o. g. studie sehr ähnlich zu sein. abstracts sagen bei schwerer herzinsuffizienz, bei dekompensierten klappenerkrankungen, mit elektrischen sturm) und mit septischem schock mit hochgradig eingeschränkter lvef der noradrenalin-verbrauch stieg unter der therapie (p = , )-von ± , auf ± , µg/kg/ h. elf ( %) patienten verstarben. zusammenfassung: durch zusätzliche gabe von levosimendan zu einer hochdosierten katecholamintherapie konnte eine sign. erhöhung des ci, jedoch ohne sign. senkung des peripheren widerstandes unabhängig von der ursache des schocks erreicht werden allerdings sind die effekte der levosimendan-und der noradrenalin-therapie schwer voneinander zu trennen der abstand der messungen mit beiden methoden betrug ± drei patienten sind im verlauf verstorben. die messungen des hi korreliert signifikant (r = . , p < . ) mit einer mittleren differenz (pac-picco) von , ± , l/min. auch das sv korreliert signifikant (r = . , p < . ) mit einer mittleren differenz von − . ± . ml. die messwerte für den svri korrelieren ebenfalls signifikant (r = . , p < . ) mit einer mittleren differenz von ± dyn sec cm- . zusammenfassung: in dieser nicht-systematischen unkontrollierten untersuchung stimmen die ergebnisse der hi, sv und svri messungen beider methoden recht gut überein. somit scheint eine picco-basierte messung hämodynamischer parameter auch unter perkutaner linksventrikulärer unterstützung möglich zu sein beginn mit kalkulierter antibiose bei v. a. tracheobronchitis; nach etwa stunden befundmitteilung: legionellen-schnelltest positiv im rö-thorax am tag deutliches infiltrat im linken oberfeld. passagere delirante symptomatik. eeg am tag ohne herdbefund oder epilepsietypische veränderungen kontroll-mrt am tag ohne befundwandel; entlassung nach hause am tag . zusammenfassung: neurologische komplikationen im rahmen von legionellen-pneumonien sind bekannt, bereiten allerdings durch ihre atypischen erscheinungsformen diagnostische schwierigkeiten hintergrund: invasive mykosen (im) sind mit einer hohen sterblichkeit assoziiert. eine frühe diagnose durch nicht-kulturbasierte nachweismethoden könnte eine zeitnahe therapie ermöglichen. ziel der studie ist es den fungalen biomarker , -beta-d-glucan (bdg) hinsichtlich einer frühen detektion einer im und als outcome-parameter bei immunsupprimierten intensivpatienten mit septischen schock zu evaluieren. methode: erhebung der bdg parameter (fungitell assay) und vergleich mit konventionellen mikrobiologischen befunden. vergleich von apa-che ii und sofa score sowie mortalität in bezug auf bdg parameter. ergebnisse: von patienten wurden ( %) immunsupprimierte patienten mit septischen schock identifiziert. ( %) patienten hatten bdg werte oberhalb des cut-off von > pg/ml (mittelwert pg/ml). ( %) patienten hatten aspergillus spp. in der bronchoalveolären lavage (bdg mittelwert pg/ml). den eortc/msg guidelines folgend wurden diese als "probable" invasive aspergillose (ia) gewertet. ( %) patienten hatten eine candidämie (bdg mittelwert pg/ml). patienten hatten deutlich erhöhte bdg parameter die den guidelines folgend auch ohne kulturelles korrelat zumindest den verdacht auf eine im nahe legen. es besteht eine allgemeine sensitivität (s) von % ( % ci - %) und spezifität (sp) von % ( % ci - %) für den bdg fungitell assay. für eine ia ergibt sich eine s von % ( % ci - %) und sp von % ( % ci - %), für eine candidämie eine s von % (ci % - %) und sp von % ( % ci - %). hinsichtlich der rolle als outcome-parameter zeigten sich im vergleich von patienten mit erhöhten bzw. nicht erhöhten bdg parametern signifikante unterschiede: apache ii score ( versus , p < , ), sofa score ( versus , p < , ) und mortalitätsrate ( % versus %, p < , ). zusammenfassung: mittels dem , -beta-d-glucan fungitell assay können frühzeitig invasive mykosen detektiert werden. darüber hinaus sind patienten mit einem erhöhten bdg dem apache ii und sofa score folgend deutlich kränker und haben eine erhöhte mortalitätsrate als solche ohne erhöhte bdg parameter. somit ist das , -beta-d-glucan nicht nur ein hilfreicher marker zur detektion von invasiven mykosen, sondern dient auch als outcome-parameter bei intensivpatienten. einen hypodynamen schock in frage. da eine vaecmo therapie keine kausale therapie darstellt, ist die prognose von der behandlung der ursache abhängig, kann als bridging therapie eine lebensrettende massnahme bei versagen einer konventionellen sepsis therapie darstellen. flunarizine suppresses endothelial angiopoietin- synthesis in a calcium -dependent fashion in sepsis j. retzlaff; k. thamm; h. haller; s. m objective: sepsis is an overwhelming systemic inflammatory response of the host to an infection. the overwhelming host response regularly leads to endothelial inflammation, barrier breakdown and multiple organ dysfunction. the vascular destabilizing factor angiopoietin- (angpt- ) has been implicated in these processes in human sepsis. here we screened in an unbiased approach fda-approved compounds with respect to endothelial angpt- suppression and investigated the underlying molecular mechanism. method: fda-library screening, in vitro analysis with standard molecular biology tools, in vivo murine endotoxemia (lps) results: we identified the t-type calcium channel (cc) blocker flunarizine being capable of suppressing angpt- release in human umbilical vein endothelial cells (huvecs) in a dose-and time-dependent fashion. moreover, flunarizine protected ecs from tnfa-induced increase in both angpt- release and biosynthesis (i. e. cellular protein and mrna). we found that compound-independent t-type cc blockade, but not l-type, was sufficient to lower angpt- and that flunarizine was ineffective when cytosolic [ca + ] concentra tion was experimentally increased by blocking the sarcoplasmic reticulum (serca) pump. of note, flunarizine was also able to block the pathological increase of angpt- transcription as well as circulating angpt- levels in murine endotoxemia in vivo. this resulted in reduced pulmonary adhesion molecule expression (icam- ) and tissue infiltration of inflammatory cells (gr- ). conclusion: in summary, we identified flunarizine to lower injurious angpt- in sepsis both in vitro and in vivo. mechanistically, this effect might be promoted via endothelial t-type cc blockade. our finding could have therapeutic implications as side effects of flunarizine are low and specific sepsis therapeutics are highly desirable. objective: tie is a receptor tyrosine kinase almost exclusively expressed on endothelial cells (ecs) that controls vascular quiescence and its response to distinct injuries. besides tie deactivation it has recently been recognized that also receptor expression per se can dramatically decrease upon various critical illnesses. importantly, we could recently show that experimental tie reduction is sufficient to mimic the septic endothelial phenotype. here we investigate putative underlying mechanisms in vivo and in vitro that might count responsible for this broad tie suppressive effect. method: standard molecular biology tools (if, wb, qpcr, elisa, sirna) in vitro, + endothelial flow experiments in vivo models of sepsis (clp and lps) human cross-sectional sepsis cohort (elisa serum stie ) results: we observed that tie was indeed rapidly suppressed both on the protein and mrna level in different murine sepsis models. challenging abstracts ergebnisse: im jahr wurde im universitätsklinikum hamburg-eppendorf bei insgesamt erwachsenen patienten ( % männlich) mit einem medianen alter von jahren (spanne - ) ein perkutanes extrakorporales kardiopulmonales unterstützungssystem (ecls) mit folgenden verfahren initiiert: va-ecmo (n = ), vv-ecmo (n = ; blutfluss > , l/min), vv-ecco r (n = ; blutfluss < , l/min), av-ecco r (n = ) und rvad (n = ). bei patienten ( , %) erfolgte eine wach-ec-mo/-ecco r zur intubationsvermeidung, bei den übrigen patienten wurde eine begleitende invasive beatmung durchgeführt. während des untersuchungszeitraumes wurden patienten ( , %) während der gesamten ecls-behandlung mindestens einmal mobilisiert. in der summe erfolgten mobilisierungen an ( , %) von insgesamt ecls-behandlungstagen. die mobilisierungen erfolgten bei episoden auf die bettkante ( , %), bei episoden in den stand ( , %), bei episoden in den sessel ( , %) und bei episoden wurden die patienten gehend auf den flur mobilisiert. die dauer der mobilisation betrug im median minuten (iq / - ). in einem fall kam es zu einer akzidentellen dislokation einer femoralen ecmo-kanüle mit erfolgreicher und folgenloser neuanlage. die seitens des ärztlich-pflegerischen behandlungsteams angegebenen gründe für ecls-behandlungstage ohne mobilisierung waren analgosedierung ( %), schlechter allgemeinzustand ( , %), komatöser zustand ohne analgosedierung ( , %), knappe personalbesetzung ( , % ergebnisse: das mittlere alter der studienpopulation lag bei , ± , jahre, der mittlere bmi bei , ± , kg/m . eine definitive abschätzung hinsichtlich des beatmungsausgangs anhand der grunderkrankung ergab sich in unserem zentrum nicht. betrachtet man in einer weitergehenden analyse die pco -werte beim ersten spontanatemversuch, so zeigt sich ein signifikant erniedrigter pco -wert (*p = , ) bei patienten, die ohne beatmung den weaningprozess abgeschlossen haben, im vergleich zu den patienten, die eine nicht-invasive ventilationstherapie im weaning benötigt haben. ein unterscheid zwischen invasiver beatmung und ohne beatmung war nicht dokumentierbar, wobei andere weaninghindernisse wie die persistierende dysphagie keine beachtung fanden. m. ritzka; s. schweiger; d. zonies ; a. philipp ; a. pross; i. göcze; t. bein operative intensivstation, klinik für chirurgie, klinik für herzchirurgie, klinik für anästhesiologie, universitätsklinikum regensburg, regensburg; landstuhl regional medical center, landstuhl;hintergrund: q-fieber ist eine weltweit verbreitete zoonose, ausgelöst vom intrazellulär lebenden, gramnegativen coxiella burnetii, und verursacht zwei syndrome: die akute und die seltene, chronifizierte erkrankung. methode: wir berichten über den dramatischen verlauf eines akuten q-fiebers, das ein -jähriger offizier in afghanistan entwickelte. nach -tägiger symptomatik mit kontinuierlichem fieber, schwitzen, erschöpfung, erbrechen und retroorbitaler cephalgie wurde er stationär aufgenommen. differentialdiagnostisch wurde sogleich ein sog. "helmand fever" erwogen. therapiert wurde mit antiphlogistika, amoxicillin und doxycyclin. bei klinischer verschlechterung mit hepatosplenomegalie und fulminant erhöhten transaminasen sowie thrombozytopenie wurde tage später levofloxacin verabreicht. es folgte eine schocksymptomatik mit schwerer hypotension, dyspnoe, azidose, gerinnungsversagen und fazial betonten Ödemen, die neben einer beatmungstherapie den kombinierten einsatz von hochdosierten vasopressoren erforderlich machte. eskalation der therapie mit ceftriaxon, doxycycline und oseltamivir. da das fortschreitende, kombinierte respiratorische versagen mit der eingeleiteten differenzierten beatmungstherapie (peep von , fio = , ) nicht mehr beherrschbar war, wurde eine veno-venöse ecmo implantiert und der patient an unser ecmo-zentrum transferiert. das ct des thorax wies die zeichen eines schweren ards sowie beidseits massive pleuraergüsse auf. einzig in einer bal vom aufnahmetag konnte coxiella burnetii (pcr-nachweis: htpab-gen) nachgewiesen werden, andere serologische und mikrobiologische untersuchungen erbrachten keine positiven befunde. aufgrund eines passageren akuten nierenversagens wurde über die ecmo auch eine sled angeschlossen. nach tagen unter ultraprotektiver beatmung und klinischer erholung mit fortgesetzter doxycyclin-und meropenem-applikation konnte der patient von der vvecmo geweant und einen tag später extubiert werden. ergebnisse: ein fulminant verlaufendes akutes q-fieber ist ein seltenes ereignis. Über den erfolgreichen einsatz einer ecmo bei q-fieber-pneumonie, die notwendig war, um mit intensivmedizinischen maßnahmen die infektion bekämpfen zu können, wurde bislang unseres wissens nach noch nicht berichtet. initial wurde die symptomatik mit kardiopulmonalem versagen als septischer schock, kompliziert durch eine anaphylaktische reaktion, gewertet. differentialdiagnostisch kann aber eine jarisch-herxheimer-reaktion nach antibiotikagabe nicht ausgeschlossen werden. hintergrund: anamnese: ein jähriger patient mit langjähriger rheumatioder arthritis und rechts-posteriorem apoplex vor monaten wird wegen seit zwei tagen bestehenden grippalen infektes und neu aufgetreter dysarthrie und ataxie eingewiesen. methode: klinischer aufnahmebefund: wacher, orientierter patient. dysarthrie und ataxie, sonst keine neurologischen pathologien. pulmo mit verschärftem atemgeräusch über dem linken oberfeld. initiale laborwerte: leukozyten , , thrombozyten (je gpt/l); ph , , po , kpa (unter l o /min), pco , kpa, be + , hco ; k+ , ; na ; hb , , kreatinin ; harnstoff , ; lactat , ; glucose (je mmol/l); crp mg/ l, pct , ng/ml, lipase, transaminasen und troponin im normbereich; liquor-diagnostik: zellzahl, lactat und glucose unauffällig, normaler albuminquotient bildgebende diagnostik: cct: z. n. posteriorinfarkt rechts ohne veränderungen zu den vorbefunden; angio-mrt: unauffällige blutversorgung des gehirns, keine blutung, keine ischämie; rö-thorax: unauffälliger herz-lungen-befund; abdomen-sono und tee ohne pathologische befunde. ergebnisse: Übernahme auf die intensivstation. dort entnahme von blutkulturen, nasenabstrich und urin zur mikrobiologischen diagnos- key: cord- -pvijxcgi authors: zhang, joe; merrick, blair; correa, genex l.; camporota, luigi; retter, andrew; doyle, andrew; glover, guy w.; sherren, peter b.; tricklebank, stephen j.; agarwal, sangita; lams, boris e.; barrett, nicholas a.; ioannou, nicholas; edgeworth, jonathan; meadows, christopher i.s. title: veno-venous extracorporeal membrane oxygenation in coronavirus disease : a case series date: - - journal: erj open res doi: . / . - sha: doc_id: cord_uid: pvijxcgi rationale: the use of veno-venous extracorporeal membrane oxygenation (vv-ecmo) in severe hypoxaemic respiratory failure from coronavirus disease (covid- ) has been described, but reported utilisation and outcomes are variable, and detailed information on patient characteristics is lacking. we aim to report clinical characteristics, management, and outcomes of covid- patients requiring vv-ecmo, admitted over months to a high-volume uk centre. methods: patient information, including baseline characteristics and clinical parameters, was collected retrospectively from electronic health records for covid- vv-ecmo admissions between rd march and nd may . clinical management is described. data are reported for survivors and non-survivors. results: we describe consecutive patients with covid- who received vv-ecmo. median age was years [iqr . – . ], . % were male. median time from symptom onset to vv-ecmo was days [iqr – . ]. all patients underwent computed tomography imaging, finding extensive pulmonary consolidation in . %, and pulmonary embolus in . %. . % received immunomodulation with methylprednisolone for persistent maladaptive hyperinflammatory state. vasopressors were used in %, and . % received renal replacement therapy. median duration on vv-ecmo was days [iqr – ]. fourteen patients died ( . %) and survived ( . %) to hospital discharge. non-survivors had significantly higher d-dimer ( . versus . mg·l(− ), fibrinogen equivalent units; p= . ) and creatinine ( versus umol·l(− ); p= . ) at commencement of ecmo. conclusions: our data supports the use of vv-ecmo in selected covid- patients. the cohort was characterised by high degree of alveolar consolidation, systemic inflammation, and intravascular thrombosis. a significant cohort of patients with coronavirus disease (covid- ) go on to develop severe respiratory failure, requiring critical care admission. reports have described the use of veno-venous extracorporeal membrane oxygenation (vv-ecmo) in a subset of critically ill patients, with utilisation ranging from % to % ( ) ( ) ( ) . vv-ecmo is indicated for patients with potentially reversible, refractory, lifethreatening hypoxaemia or hypercapnia, or in patients where acceptable oxygenation or decarboxylation can be obtained only with injurious ventilatory settings. while vv-ecmo was associated with improved outcome during the h n influenza pandemic ( , ) , covid- demonstrates features unique from other respiratory infections and early case-series have reported high mortality in patients on ecmo ( ) ( ) ( ) . given the lack of detailed information about patient characteristics and their clinical course, balanced with the need for judicious use of resources in the context of a pandemic, it is important to understand the role of vv-ecmo in covid- . we aim to describe, in detail, the clinical characteristics, management and outcomes of covid- vv-ecmo patients from a high-volume uk ecmo centre, over a twomonth period of the pandemic. all covid- patients admitted for vv-ecmo to guy's and st thomas' nhs foundation trust (gstft) in london, over a two-month period ( rd march to nd may ) covering the peak of the pandemic, are included. suitability for vv-ecmo was assessed in line with uk national commissioning criteria ( ) , requiring a lung injury (murray) score ≥ ( ) , or uncompensated hypercapnic acidosis with ph < . . national criteria were adapted for the covid- pandemic on the th of april ( ) to include clinical frailty scale ≤ ( ) , the use of the respiratory ecmo survival prediction (resp) score ( ) to aid pre-ecmo decision-making (with resp score ≤ requiring agreement between at least two centres), and an exclusion of "refractory multi-organ failure". at the time of this series, detection of sars-cov- rna on nose and throat swabs or bronchoalveolar lavage (bal) using multiplexedtandem polymerase chain reaction technology for detection of gene targets, orf a and orf (ausdiagnostics, mascot, australia), remained gold standard. all patients, at point of referral, had either laboratory confirmed or clinically suspected covid- pneumonia; four patients without a positive result at time of referral subsequently tested positive from admission samples at gstft. gstft is a national vv-ecmo centre commissioned to provide regional ecmo retrieval and provision ( ) . at the start of the pandemic, gstft ecmo capacity was doubled through adaptation of each bedspace to accommodate two patients on ecmo. patients were retrieved from referring hospitals via a previously described standard pathway ( ) , with no deviation in practice aside from use of recommended personal protective equipment. standard gstft practice is bifemoral percutaneous cannulation at the referring hospital, and use of maquet cardiohelp (maquet, rastatt, germany) consoles. following retrieval, all patients underwent computed tomography (ct) imaging of head, thorax (including ct pulmonary angiogram), abdomen and pelvis. lung recruitment ct imaging at ventilator pressures of cmh o and cmh o were performed, unless pneumothorax was detected on initial scan or pulmonary air leak was suspected, to assess lung recruitment potential and delineate underlying lung parenchyma ( ) . diagnostic bronchoscopy and bal for bacterial culture, viral and sars-cov- pcr was performed on all patients within the first hours. patients without haemorrhagic complications were anticoagulated with unfractionated heparin infusion, targeting anti-xa levels ( . - . ui/ml). patients were ventilated with protective lung parameters. mechanical ventilation was generally initiated using standardised settings: peep - cmh o, tidal volume - ml/kg of predicted body weight provided that driving pressure (plateau minus peep total) could be kept at cmh o, and plateau pressure < cmh o. initial respiratory rate was generally maintained at breaths/minute to limit overall mechanical power ( ) . in patients with high potential for lung recruitmentas patients received a course of broad-spectrum antibiotics on arrival, targeted to known microbiology where possible. a subset of patients with failure to progress and signs of a sustained hyperinflammatory state (fevers, persistently elevated creactive protein and/or ferritin, sustained organ dysfunction and hypoxaemia), in the absence of untreated active infection (bacteria or fungal species detected on blood culture and bal, low procalcitonin and galactomannan), were treated with low dose methylprednisolone regimens of - mg/kg/day for - days, with halving in dose every - days, similar to published protocol ( ) . this dosing regimen was chosen for its relative safety profile ( , ) . patients with persistent hyperinflammatory disease behaviour despite corticosteroids, or those with an "h score" greater than suggesting secondary haemophagocytic lymphohistiocytosis ( , ) were considered for treatment with the il- receptor antagonist anakinra ( , ) . patients with persistent hypoxaemia and radiological abnormality despite low dose corticosteroids, or patients who demonstrated early fibrosis on ct, were treated with high dose "pulsed" methylprednisolone at doses of g for days, followed by mg/kg per day, followed by a weaning regimen. treatments were given in consultation with local lung inflammation specialists. patients generally remained paralysed for an initial hours, particularly if strong inspiratory efforts persisted despite adequate sedation, or if asynchronies due to deep sedation were noted (e.g. reverse triggering). daily sedation wean was then undertaken in stable patients to maximise wakefulness. a specialist physiotherapy team assessed patients on a daily basis for both secretion clearance, and early rehabilitation. ventilation weaning was based on daily assessment of lung mechanics, as well as ability to spontaneously ventilate without injurious tidal volumes, respiratory rate and inspiratory effort (including measurements of p . - ms airway occlusion pressure), that might contribute to patient self-inflicted lung injury (p-sili). criteria for decannulation from vv-ecmo in this cohort included maintained fractional inspired oxygen < . and non-injurious ventilatory effort, with ecmo sweep gas turned off for at least hours. the full protocol of weaning from vv-ecmo is described and available ( ) . data was collected retrospectively from electronic records, including the intellivue clinical information portfolio (phillips, eindhoven, the netherlands). pre-ecmo data were obtained from ecmo referral systems( ), paper records, or direct interview with members of retrieval teams. resp score was calculated at the time of referral. forty-three patients with covid- were accepted and admitted for vv-ecmo based on the listed criteria, out of patients referred to gstft during the study - ] days, and median from invasive ventilation to vv-ecmo was days [ - ] . the acute kidney injury (creatinine ≥ umol/l) was a common feature ( patients, . %). data is shown in table . twenty-nine patients ( . %) were successfully decannulated from vv-ecmo and survived until hospital discharge. twelve ( . %) patients died on ecmo, and two the mortality described in this vv-ecmo series ( of , . %) is lower than in early descriptions. patients exhibited particular characteristics including poor lung compliance, persistent hyperinflammation, and high incidence of thrombosis. survival in this series is comparable to more recent data from the usa( ) and france ( ) . since the study period, a further patients have completed vv-ecmo at gstft, with overall survival to icu discharge at . %. the pattern of disease seen in our cohort has been previous described. exudative lung disease with poor compliance (as described by gattinoni et al( ) ), persistent hyperinflammation ( , ) , and increased thrombosis incidence may demonstrate a particular phenotype that defines a later stage of the disease process. median ferritin and d-dimer seen at ecmo initiation were comparable to values seen after two weeks in a cohort of non-surviving hospitalised patients ( ) . a majority of our patients were given immunomodulation ( ) after risks of immunosuppressing critically ill patients ( ) the incidence of pe ( . %) was substantially higher than in pre-covid- ( . %) in the same centre ( ) , carrying substantial morbidity in our cohort with rv dysfunction in %. cannula-related thrombosis rates ( . %) were greater than baseline prevalence ( ) , and ecmo membrane complication rate was similarly high. thrombosis risk is a known entity in severe covid- ( ) , but adjusted anticoagulation targets must be balanced against higher risk of haemorrhagic complication in ecmo ( ) , the cause of multiple complications and one death in our cohort. at time of writing, no published literature specifically addresses secondary or coinfection in covid- ecmo. these individuals may represent a distinct cohort microbiologically. the unusual predominance of klebsiella spp has been seen elsewhere, as has candida spp ( , ) , but remains a focus of further analysis in gstft regarding infection control consequences of doubling bedspace usage. admission procalcitonin was elevated in all patients, but significantly greater procalcitonin in the non-survivor group may have limited earlier use of steroids. reactivation or flares of chronic viral infections including cmv must also be considered, especially in those receiving immunomodulation. following new commissioning criteria in the uk, the threshold for acceptance of patients onto vv-ecmo has been reinforced by the inclusion of the resp score. this predictive score is validated in patients already on ecmo( , ), but not as a pre-ecmo decision tool. the resp score was one component of a multi-tool assessment process when deciding which patients should be offered vv-ecmo, and cases with low resp scores were discussed with a second centre if ecmo was felt to be indicated. validation of this tool in the uk ecmo population may help guide future usage. this series has the inherent limitations of a single-centre study, conducted in a wellresourced and experienced centre, during the early stages of our understanding in a new disease. it is likely that aspects of management will differ over time and between centres, as our understanding of how to treat particular phenotypes improves in any future pandemic waves. this case series suggests that vv-ecmo, when offered to patients with covid- respiratory failure refractory to conventional ventilatory management, can be associated with a favourable outcome. in covid- patients with severe respiratory failure, early consultation with an ecmo centre and joint decision-making on suitable support modality is a key strategy. 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cytokines including interleukin- in covid- induced pneumonia and macrophage activation syndrome-like disease the pathogenesis and treatment of the `cytokine storm' in covid- clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study immunosuppression for hyperinflammation in covid- : a double-edged sword? chief investigators of the randomised evaluation of covid- therapy (recovery) trial on dexamethasone. low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of covid- screening pulmonary angiogram and the effect on anticoagulation strategies in severe respiratory failure patients on venovenous extracorporeal membrane oxygenation prevalence of venous thrombosis following venovenous extracorporeal membrane oxygenation in patients with severe respiratory failure clinical research in intensive care and sepsis trial group for global evaluation and research in sepsis) high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study bacterial and fungal co-infection in individuals with coronavirus: a rapid review to support covid- antimicrobial prescribing co-infection with respiratory pathogens among covid- cases predicting survival after extracorporeal membrane oxygenation for ards: an external validation of resp and preserve scores key: cord- - uty rwi authors: joyce, david l. title: mechanical ventilation: a necessary evil? date: - - journal: j thorac cardiovasc surg doi: . /j.jtcvs. . . sha: doc_id: cord_uid: uty rwi nan a necessary evil? to the editor: the avoidance of ventilatorassociated lung injury has been a hallmark of acute respiratory distress syndrome management for the past years. although recent clinical trials have failed to establish the superiority of mechanical circulatory support over mechanical ventilation in these patients, extracorporeal membrane oxygenation (ecmo) has traditionally been reserved for refractory cases and most often performed through femoral cannulation. with a surgical volume of over cases, our program has one of the largest experiences with the protek duo right ventricular assist device cannula (livanova, london, united kingdom). percutaneous cannulation via the right internal jugular vein allows for full right ventricular and pulmonary support in which blood is withdrawn from the right atrium, oxygenated, and returned directly to the pulmonary artery ( figure ). as with other disruptive transcatheter technologies, the skill set required for procedural success exists at the intersection of interventional cardiology and cardiac surgery. a collaborative approach between these disciplines was critical during our initial implants and can effectively negate the risks of inexperience. early in our experience, we observed that right ventricular dysfunction was frequently attributed to distributive shock. recognizing that acute respiratory distress syndrome in the context of covid- frequently leads to increasing pressor requirements and progression to multiple organ dysfunction syndrome, we hypothesized that early intervention with a percutaneous right ventricular assist device/ecmo approach might improve outcomes in these patients. in consecutive patients, we have not had any secondary organ failure, with only mortality. pressor requirements have been eliminated with this approach, and our practice has been to extubate while on ecmo support to facilitate rehabilitation and avoid ongoing barotrauma. at the time of this submission, of the patients have been decannulated. although all the patients met extracorporeal life support organization criteria for support, attempts were made to intervene at the time of intubation to minimize the adverse effects of mechanical ventilation. cost considerations weigh heavily on the decision to proceed with any form of mechanical circulatory support, and the pandemic-induced economic uncertainty facing hospitals has only added to the complexity of these decisions. charges for a -day hospital stay in of our patients totaled $ , . although supply chain limitations would likely impair the widespread adoption of this approach, the current spoke-hub model for ecmo referral potentially could mitigate many of the economic disparities between hospitals. anecdotal evidence should always be viewed with a degree of skepticism, and our team is currently preparing for a multicenter prospective randomized clinical trial to evaluate the merits of this approach compared with conventional management strategies. nevertheless, cardiothoracic surgeons who are asked to cannulate a patient for covid- in the setting of increasing pressor requirements or secondary organ failure should carefully evaluate the potential for right ventricular dysfunction as a contributor. the author reported no conflicts of interest. the journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. the editors and reviewers of this article have no conflicts of interest. acute respiratory distress syndrome key: cord- -ql moyi authors: hong, david; choi, ki hong; cho, yang hyun; cho, su hyun; park, so jin; kim, darae; park, taek kyu; lee, joo myung; song, young bin; choi, jin-oh; hahn, joo-yong; choi, seung-hyuk; choi, jin-ho; sung, kiick; gwon, hyeon-cheol; jeon, eun-seok; yang, jeong hoon title: multidisciplinary team approach in acute myocardial infarction patients undergoing veno-arterial extracorporeal membrane oxygenation date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: ql moyi background: limited data are available on the impact of a specialized extracorporeal membrane oxygenation (ecmo) team on clinical outcomes in patients with acute myocardial infarction (ami) complicated by cardiogenic shock (cs). this study evaluated whether specialized ecmo team is associated with improved in-hospital mortality in ami patients undergoing veno-arterial (va) ecmo. methods: a total of ami patients who underwent va-ecmo were included. in january , a multidisciplinary ecmo team was founded at our institution. eligible patients were classified into a pre-ecmo team group (n = ) and a post-ecmo team group (n = ). the primary outcome was in-hospital mortality. results: in-hospital mortality (pre-ecmo team vs. post-ecmo team, . % vs. . %; p = . ) and cardiac intensive care unit mortality (pre-ecmo team vs. post-ecmo team, . % vs. . %; p = . ) were significantly lower after the implementation of a multidisciplinary ecmo team. on multivariable logistic regression model, implementation of the multidisciplinary ecmo team was associated with reduction of in-hospital mortality [odds ratio: . , % confidence interval (ci) . – . ; p = . ]. incidence of all-cause mortality [ . % vs. . %; hazard ratio (hr): . , % ci . – . ; p < . ) and readmission due to heart failure ( . % vs. . %; hr: . , % ci . – . ; p = . ) at months of follow-up were also significantly lower in the post-ecmo team group than in the pre-ecmo team group. conclusions: implementation of a multidisciplinary ecmo team was associated with improved clinical outcomes in ami patients complicated by cs. our data support that a specialized ecmo team is indispensable for improving outcomes in patients with ami complicated by cs. cardiogenic shock (cs) is the main cause of mortality in patients with acute myocardial infarction (ami) [ , ] . despite advancements in reperfusion and pharmacological therapy, the short-term mortality rate of patients with ami complicated by cs remains unacceptably high [ , ] . particularly, in refractory cs not responding to open access *correspondence: jhysmc@gmail.com † david hong and ki hong choi contributed equally to this work division of cardiology, department of internal medicine, heart vascular stroke institute, samsung medical center, sungkyunkwan university school of medicine, irwon-ro, gangnam-gu, seoul , republic of korea full list of author information is available at the end of the article conventional medical therapies, in-hospital mortality rate reaches % to % [ , ] and mechanical support such as veno-arterial (va) extracorporeal membrane oxygenation (ecmo) is recommended in both the latest american heart association and the european society of cardiology guidelines (classes iia and iib, respectively) [ , ] . these poor outcomes are due to complex and hemodynamically diverse state of cardiogenic shock [ , ] . the high-acuity of maintaining ecmo and the interaction between native heart and va-ecmo may also be related to the poor outcomes [ , ] . in particular, running va-ecmo is associated with many serious complications, which may contribute to further increase in morbidity and mortality [ , [ ] [ ] [ ] . accordingly, related organizations recommended that these patients be managed by a collaborative multidisciplinary team with trained specialists [ , ] . however, for ami complicated by cs, which is the most common cause for the use of va-ecmo [ ] , the impact of a multidisciplinary approach on the clinical outcome has not been investigated. therefore, we sought to identify whether a multidisciplinary ecmo team is associated with improvements in in-hospital mortality among patients with ami complicated by cs who underwent va-ecmo. the study population was derived from the prospective institutional va-ecmo registry of samsung medical center in seoul, republic of korea from may to july (fig. ) . from this registry, ami patients complicated by cs were included in the analysis. ami was defined as evidence of myocardial injury (defined as an elevation of cardiac troponin values, with at least one value above the th-percentile upper-reference limit) with necrosis in a clinical setting, consistent with myocardial ischemia [ ] . cs was defined as persistent hypotension (systolic blood pressure < mmhg) for min or a state that required inotrope or vasopressor support to achieve a systolic blood pressure of more than mmhg despite adequate filling status, with signs of hypoperfusion [ ] . va-ecmo was applied to patients with medically refractory cs that did not respond to inotropes and vasopressors, or cardiac arrest that was not resuscitated with advanced cardiac life support [ , ] . patients who received va-ecmo due to stable angina, unstable angina, and variant angina were excluded from this study. patients, who were clinically stable before revascularization, but received va-ecmo for prophylactic purpose because of their poor cardiac function and high risk of expected treatment, were also excluded from the study. finally, patients were analyzed. as of the date the multidisciplinary ecmo team was founded at our institution, patients were classified into two groups: a pre-ecmo team group (before january , n = ) and a post-ecmo team group (after january , n = ). the institutional review board of samsung medical center approved this study, and written informed consent was obtained. our institution is a tertiary referral hospital with a tertiary-level intensive care unit. since the initiation of the use of ecmo in , the number of patients treated with ecmo had increased gradually. currently, more than patients are treated with ecmo each year at our institution. cardiac surgeons or interventional cardiologists inserted va-ecmo at bedside or in the catheterization laboratory. as far as there were no special indications, peripheral cannulation with percutaneous approach using the seldinger technique was chosen as the initial implant method. the capiox emergency bypass system (capiox ebs ™ ; terumo, inc., tokyo, japan) and permanent life support (pls; maquet, rastatt, germany) were used in our hospital. all patients received unfractionated heparin as an anticoagulant unless there was active bleeding. through our hospital's own protocol, the heparin infusion rate was adjusted to achieve the target activated clotting time of to s and activated partial thromboplastin time of to s, respectively. in the event of persistent pulmonary edema after ecmo initiation despite diuresis and inotropes, left ventricular decompression was achieved by either percutaneous atrial septostomy or surgical venting. in january , a multidisciplinary ecmo team was founded at our institution. our ecmo team consists of interventional cardiologists, critical care physicians, cardiovascular surgeons, heart failure physicians, a pharmacist, a nutritionist, and perfusionists who were formal intensive care registered nurses and received specific ecmo training. before the team's establishment, attending physician, who was capable of inserting and maintaining ecmo, was responsible for running ecmo. most of the ecmo-related decisions, from initiation to weaning, were made solely by the attending physician. instaff training was in charge of attending physician as well. no protocol existed for maintaining ecmo. only elective consultation to experienced cardiothoracic surgeons was possible in difficult clinical situations, with no -h on-call coverage by an ecmo specialist. however, after the foundation of the ecmo team, team members readily participated in the management of ecmo patients and all ecmo-related decisions, as described below. first, both the initiating and weaning of ecmo were performed under the supervision of the ecmo team. based on our institutional ecmo protocols for indications and contraindications (additional file : table s ), the ecmo team evaluated the eligibility of the patient for ecmo and made the final decision of whether to initiate ecmo or not. the decision of weaning was also made together by the attending physician and ecmo team based on our institutional weaning criteria. second, as part of daily rounds, echocardiography was performed to evaluate cardiac function and recovery. the pharmacist and nutritionist adjusted prescribed medications and nutritional plan in accordance with alterations of pharmacokinetics and metabolic status due to running ecmo and the critically ill status of the patient. also, the ecmo team checked the functional status of the ecmo device including the pump, oxygenator, and cannula daily, and assessed the occurrence of ecmo-related complications and the adequacy of relevant management. third, ecmo-trained physicians, cardiovascular surgeons, and perfusionists provided -h on-call coverage for ecmo patients and potential candidates. fourth, the ecmo team was responsible for staff training. doctors and nurses who were in charge of ecmo patients were educated by the ecmo team in order to properly manage patients according to their complicated clinical situations. fifth, a weekly meeting was held to discuss the issues of current ecmo patients as well as review previous cases for quality assurance. patient management was performed according to current standard guidelines [ , , , ] . the choice of treatment strategy of percutaneous coronary intervention (pci) (type, diameter, and length of stents; use of intravascular ultrasound; glycoprotein iib/iiia inhibitor use; and thrombus aspiration) was left to the discretion of the attending physicians. unless there was an undisputed reason for discontinuing dual-antiplatelet therapy, all patients were recommended to take aspirin indefinitely plus a p y inhibitor for at least year after the index procedure. coronary artery bypass graft (cabg) was performed using current standard methods. the left internal mammary artery was considered preferential for revascularization of the left anterior descending artery. patients who underwent cabg were recommended to take aspirin indefinitely. if intolerant to aspirin, taking clopidogrel as an alternative was also allowed. patients were prospectively registered at the time of index hospitalization. demographic feature and cardiovascular risk factor data were collected by detailed interview with patients or their families at admission. coronary angiographic findings and procedural history of pci, cabg, and ecmo were gathered during hospitalization. information about adjunctive therapies in addition to ecmo such as inotropes, mechanical ventilation, and continuous renal replacement therapy was collected at the time of discharge. follow-up outcomes were obtained from the review of patients' electronic medical records by research coordinators of the dedicated registry. clinical events that occurred within a -month follow-up period were analyzed. the primary outcome was in-hospital mortality. secondary outcomes included cardiac intensive care unit (cicu) mortality, -month all-cause death, -month readmission due to heart failure, successful weaning of ecmo, complications in the cicu, length of cicu stay, duration of ecmo, duration of mechanical ventilation, and duration of continuous renal replacement therapy. all clinical outcomes were defined according to the academic research consortium [ ] . all deaths were considered cardiac-related unless a definite non-cardiac cause could be established. successful weaning of ecmo was defined as maintaining hemodynamic stability after ecmo removal with or without getting durable left ventricular assist device or heart transplantation. included complications were major bleeding, vascular complications, infection, and limb ischemia. major bleeding was defined as bleeding in the brain, thorax, mediastinum, gastrointestinal tract, or abdomen or any fatal bleeding requiring transfusion or intervention. vascular complications included vessel perforation, arterial dissection, and site bleeding. site bleeding that was fatal was not included in vascular complications and included in major bleeding. minor complications such as local hematoma were not recorded in vascular complications. infection was defined as the presence of clinical symptoms or signs of infection with concurrent microbiological evidence of infection confirmed by blood culture during cicu stay. limb ischemia was defined as cases requiring surgical management or having dependent performance from to scale on functional ambulation classification resulting from limb ischemia at discharge [ ] . categorical variables were presented as numbers and relative frequencies and compared using the chi-square test or fisher's exact test, as appropriate. continuous variables were presented as mean ± standard deviation or median with interquartile range (q to q ) and compared using the student's t test or the wilcoxon rank-sum test, as appropriate. the risk of in-hospital mortality was compared using logistic regression analysis and was presented as odds ratios (or) and % confidence intervals (ci). to identify independent predictors of in-hospital mortality, multivariable logistic regression analysis was performed. variables were included in the analysis if they showed a significant relation in the univariate analysis with a p value of less than . and were considered clinically relevant. cumulative incidences of clinical outcomes were calculated by kaplan-meier estimates and compared using a log-rank test. cox proportional hazards regression analysis was performed to compare the risk of clinical events before and after the ecmo team establishment. risks of clinical events were presented with hazard ratios (hr) and % cis. all probability values were two-sided and p-values of less than . were considered statistically significant. statistical analyses were performed using the r statistical software (version . . ; r foundation for statistical computing, vienna, austria). baseline clinical and angiographic characteristics are shown in table . of the total patients, . % presented with st-segment elevation myocardial infarction (stemi), . % had out-of-hospital cardiac arrest, and . % had in-hospital cardiac arrest. as for angiographic profile, the left anterior descending artery and left main coronary artery accounted for . % and . % of the culprit vessels, respectively. a total of . % of patients presented with multivessel disease. nevertheless, there were no differences in baseline clinical and angiographic characteristics between the two groups, except for body mass index, previous history of myocardial infarction and pci, and baseline total bilirubin. also, indicators of severity in ecmo patients such as encourage score, ami-ecmo score, and sofa score were not different between the two groups. regarding treatment characteristics (table ) , successful revascularization through either pci or cabg was higher in the post-ecmo team group than in the pre-ecmo team group ( . % vs. . %; p = . ). in stemi patients, door-to-balloon time was shorter in the post-ecmo team group than in the pre-ecmo team group ( . vs. . , p = . ). extracorporeal cardiopulmonary resuscitation was performed in . % of study population and there was no significant difference in proportion between the two groups. arrest to ecmo pump-on time (for extracorporeal cpr patients only) and shock to ecmo pump-on time (for non-extracorporeal cpr patients only) were numerically shorter in the post-ecmo group than the pre-ecmo group, with no statistical significance. for supplementary treatments after ecmo insertion, the use of inotropes or vasopressors, intra-aortic balloon pump, and mechanical ventilation was significantly lower, whereas distal perfusion was more frequently performed in the post-ecmo team group than in the pre-ecmo team group. clinical outcomes are presented in table . in-hospital mortality occurred in patients ( . %) and cicu mortality occurred in patients ( . %). in-hospital mortality ( . % vs. . %; p = . ) and cicu mortality ( . % vs. . %; p = . ) were significantly lower in the post-ecmo team group than in the pre-ecmo team group (fig. ) . the lower rate of in-hospital mortality in the post-ecmo team group was mainly driven by the lower rate of cardiovascular death ( . % vs. . %; p = . ). however, there were no significant differences between the two groups regarding non-cardiovascular death ( . % vs. . %; p > . ). clinical outcomes at months of follow-up showed consistent findings in relation with the primary outcome (fig. ) . the multidisciplinary team approach was associated with significantly lower risk of all-cause death ( . % vs. . %; hr: . , % ci . - . ; p < . ) and readmission due to heart failure ( . % vs. . %; hr: . , % ci . - . ; p = . ) at months of follow-up. regarding the management of va-ecmo patients in the cicu, specific parameters are compared in table and additional file : table s . the successful weaning of va-ecmo ( . % vs. . %; p = . ) was higher in the post-ecmo team group than in the pre-ecmo team group. however, the length of cicu stay did not differ significantly between the two groups. also, the duration of ecmo, mechanical ventilation, and continuous renal replacement therapy were longer in the post-ecmo team group than in the pre-ecmo team group. as for complications (i.e., major bleeding, vascular complication, infection, limb ischemia), each component tended to be lower in the post-ecmo team group than in the pre-ecmo team group, resulting in a statistically significant decrease in overall complications in the post-ecmo team group ( . % vs. . %; p = . ). age, out-of-hospital cardiac arrest, successful revascularization, use of mechanical ventilation, use of continuous renal replacement therapy, annual ecmo volume and the multidisciplinary ecmo team approach showed significant relation in the univariable analysis and were included in multivariable logistic regression model (table ). in this model, the multidisciplinary ecmo team approach was associated with decreased risk of in-hospital mortality (adjusted or: . , % ci . - . ; p = . ). the current study is the first to evaluate the impact of a multidisciplinary ecmo team approach on clinical outcomes in ami patients complicated by cs using data from a prospective va-ecmo registry. the main findings were as follows. first, in-hospital mortality and cicu mortality were significantly lower in the post-ecmo team group than in the pre-ecmo team group. second, the risks of all-cause death and readmission due to heart failure at -month follow-up were also significantly lower in the post-ecmo team group than in the pre-ecmo team group. third, in a multivariable logistic regression model, multidisciplinary team approach was associated with decreased risk of in-hospital mortality in ami patients with cs undergoing va-ecmo. although multidisciplinary team approach has been recommended in the care of critically ill patients, only a few studies to date have addressed its effects on clinical outcomes [ , ] . also, even though the american heart association recommended that patients with cs be managed by a multidisciplinary team [ ] , nonetheless, this recommendation was primarily based on expert opinions and research regarding the association of hospital volume with clinical outcomes in cs patients, not the multidisciplinary approach [ , ] . furthermore, considering that inserting ecmo is a high-risk intervention and maintaining ecmo requires highly sophisticated measures, the extracorporeal life support organization guidelines recommended that ecmo be operated by multidisciplinary team including trained specialists [ ] . however, there are no data about the relationship between multidisciplinary care and clinical outcomes in ami patients complicated by cs undergoing va-ecmo. therefore, we aimed to investigate the impact of multidisciplinary approach in this setting and demonstrated its beneficial effect, including reduction in mortality. our study has several strengths. a large number of patients were observed for a sufficient follow-up period of months considering that the study population was extremely severely ill patients with cs. also, mortality as well as various treatment strategies and secondary outcomes were compared before and after the introduction of the multidisciplinary ecmo team. lastly, the study population was extracted from a large prospective registry of a tertiary university hospital that reflects the real-world population and practices. the in-hospital mortality in our study before multidisciplinary team introduction was . %, similar to that of other multicenter studies ( - %) [ , ] . therefore, our study suggested that, in addition to contemporary practice of cs, the additional benefit of a multidisciplinary approach might exist. the reasons how the multidisciplinary approach improved clinical outcomes are multifactorial in the current study. first, the multidisciplinary team consisted of experts from diverse fields. thereby, the multidisciplinary approach enabled critically ill cs patients to receive systematic care and at the same time appropriate treatment for each problem. as a team leader, the critical care physician was closely involved and coordinated the multidisciplinary approach in order to properly manage multifaceted acute critical care [ ] . heart failure physicians were also involved in the treatment from the beginning of the initial state of shock and contributed to improve mortality not only by providing acute heart failure care, but also by maintaining the patient's long-term cardiac function and stably directing the process toward implementing exit strategies such as ventricular assist devices and heart transplantation for indicated patients [ ] . furthermore, a pharmacist and nutritionist were included in the multidisciplinary team. the adjustment of medications according to the altered pharmacokinetics of ecmo patients led to the maintenance of drugs at the appropriate therapeutic levels without side effects [ , ] . likewise, customizing nutritional delivery according to table predictors of in-hospital mortality c-statistic of the logistic regression model for in-hospital mortality was . ( % ci . - . ) entered variables in univariate analysis for evaluating significant relation with the primary outcome included multidisciplinary approach, age, male, body mass index, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, history of myocardial infarction, history of percutaneous coronary intervention, history of cerebrovascular accident, st-segment elevation myocardial infarction, out-of-hospital cardiac arrest, left ventricular ejection fraction, laboratory findings in table , anterior infarction, multivessel disease, percutaneous coronary intervention, coronary artery bypass graft, extracorporeal cardiopulmonary resuscitation, insertion of ecmo before revascularization, distal perfusion, use of inotropes or vasopressors, use of intra-aortic balloon pump, use of mechanical ventilation, use of continuous renal replacement therapy, overall complications and annual ecmo volume ci confidence interval, ecmo extracorporeal membrane oxygenation, or odds ratio [ , ] . second, our institutional maintenance strategies of ecmo patients were changed in order to reduce ischemic time after multidisciplinary team implantation. if cardiopulmonary resuscitation (cpr) persisted for longer than min without the return of spontaneous circulation, the ecmo team was activated and extracorporeal cpr was immediately started, unless a patient was contraindicated to receive ecmo. also at least one primed ecmo circuit was always prepared in advance at our institution. as a result, in stemi patients, doorto-balloon time was significantly shorter in the post-ecmo group than in the pre-ecmo group. also arrest to ecmo pump-on time and shock to ecmo pump-on time showed shorter tendency in the post-ecmo team group than in the pre-ecmo team group. third, various efforts were made to reduce ecmorelated complications. during daily rounds, evaluation of cardiac function through echocardiography and modifications of clinical settings were made in order to maintain appropriate hemodynamic status. these efforts have contributed to prevent organ damage due to ischemia or overperfusion. also, multidisciplinary team assessed the risk of ecmo-related complications by checking physical examinations and related laboratory results on a daily basis. in addition, as one of the changes in our institution's ecmo maintenance strategies, awake ecmo was pursued unless pulmonary gas exchange was insufficient to cause upper body hypoxia. in our study, the use of mechanical ventilation was significantly lower in the post-ecmo team group and this may have played an important role in avoiding complications related to mechanical ventilation and sedation [ ] . lastly, mandatory distal perfusion, which was reported to reduce limb ischemia and even improve `survival [ ] , was strongly recommended. as a result, all of these diverse efforts significantly reduced the incidence of complications after the team establishment, which was considerably lower than the values shown in other studies [ ] . as limitations, first, this study was an observational, prospective registry based, single-center study. consequently, the influence of confounding bias or selection bias affecting the results of the research cannot be excluded. although multivariable adjusted analysis was performed by adding various variables, the effects of confounding variables, such as annual ecmo volume or the learning curve of ecmo, were not completely corrected. therefore, the results may be influenced by multifactorial causes other than multidisciplinary team. furthermore, there might be concern about differences between the two groups when selecting patients who were appropriate candidates for using va-ecmo. however, considering that selecting appropriate patient with team-based and protocolized decision is the effect of the multidisciplinary team, this can be considered as one of benefit of multidisciplinary team rather than the selection bias. second, the advances in the treatment of shock patients or accumulation of experiences over time may have served as potential bias in the study. during the study period, three major randomized trials in ami patients by cs were done [ , , ] . first two studies were conducted to investigate the prognostic implications of immediate multivessel pci and iabp, respectively, and showed no significant difference in mortality [ , ] . on the other hand, subgroup analysis of the other study, that compared the effects of vasopressors in patients with cs, showed survival benefit of norepinephrine over dopamine [ ] . these advancements seemed to have played some role in improving the clinical results. however, as shown in fig. , when the patients who were treated before the multidisciplinary team establishment ( - ) were divided into two groups according to time, there was no significant difference in clinical outcomes between the two groups. on the other hand, there was a significant improvement in mortality between before and after . considering there was no major change in patient management other than the foundation of the multidisciplinary team, this improvement could be regarded as an additional benefit of multidisciplinary approach on the top of other advances in practice strategy or the accumulation of experiences. third, our data could not show in detail how multidisciplinary approach affected mediating outcomes and which mediating outcomes were improved, that led to decreased mortality. this is a limitation of our retrospective study, in which data were insufficiently investigated. further thoroughly investigated prospective study is needed to elucidate the detailed influence of multidisciplinary approach. fourth, the multidisciplinary approach did not show a significant reduction in the duration of cicu stay and adjunctive treatment. nonetheless, the interpretation of this result should be done with caution. this result might be related with the ability of multidisciplinary team to maintain patients stable 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statement from the american heart association awake" extracorporeal membrane oxygenation (ecmo): pathophysiology, technical considerations, and clinical pioneering fluoroscopyguided simultaneous distal perfusion as a preventive strategy of limb ischemia in patients undergoing extracorporeal membrane oxygenation comparison of dopamine and norepinephrine in the treatment of shock one-year outcomes after pci strategies in cardiogenic shock publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : table s . indications and contraindications for va-ecmo deployment. table s . duration of organ support and cicu stay. ami: acute myocardial infarction; cabg: coronary artery bypass graft; cicu: cardiac intensive care unit; cpr: cardiopulmonary resuscitation; cs: cardiogenic shock; ecmo: extracorporeal membrane oxygenation; pci: percutaneous coronary intervention; stemi: st-segment elevation myocardial infarction; va: veno-arterial. key: cord- -m zgn authors: stokes, john w.; gannon, whitney d.; sherrill, wren h.; armistead, leslie b.; bacchetta, matthew; rice, todd w.; semler, matthew w.; casey, jonathan d. title: bleeding, thromboembolism, and clinical outcomes in venovenous extracorporeal membrane oxygenation date: - - journal: crit care explor doi: . /cce. sha: doc_id: cord_uid: m zgn objectives: bleeding and thromboembolism are common during venovenous extracorporeal membrane oxygenation. the relative frequency of these complications and their impact on clinical outcomes have not been described, and no randomized trials exist to guide anticoagulation strategies in extracorporeal membrane oxygenation. our objective was to examine the relative frequencies of bleeding and thromboembolic events and their associations with survival among a cohort of consecutive patients receiving venovenous extracorporeal membrane oxygenation. design: retrospective cohort study. setting: a single academic medical center. patients: adult patients receiving venovenous extracorporeal membrane oxygenation and anticoagulation. eligibility criteria for this analysis were selected to emulate the population that would be recruited for a randomized trial of anticoagulation strategies during venovenous extracorporeal membrane oxygenation. patients were excluded if they had active bleeding or thromboembolism prior to extracorporeal membrane oxygenation initiation, a history of trauma or surgery in the days prior to extracorporeal membrane oxygenation initiation, an arterial extracorporeal membrane oxygenation cannula, or if they received greater than hours of extracorporeal membrane oxygenation support at another institution interventions: none. measurements and main results: outcomes included bleeding and thromboembolic events, duration of extracorporeal membrane oxygenation support, hospital length of stay, and in-hospital survival among patients receiving venovenous extracorporeal membrane oxygenation. bleeding events occurred in patients ( . %), and thromboembolism occurred in eight patients ( . %). bleeding events were associated with longer duration of extracorporeal membrane oxygenation support (p = . ) and worse in-hospital survival (p = . ). thromboembolic events did not appear to be associated with clinical outcomes. conclusions: in this cohort of patients receiving venovenous extracorporeal membrane oxygenation and anticoagulation, bleeding occurred more frequently than thromboembolism and was associated with worse survival. these results highlight the need for randomized trials to evaluate the safety and efficacy of continuous iv anticoagulation among patients receiving venovenous extracorporeal membrane oxygenation. objectives: bleeding and thromboembolism are common during venovenous extracorporeal membrane oxygenation. the relative frequency of these complications and their impact on clinical outcomes have not been described, and no randomized trials exist to guide anticoagulation strategies in extracorporeal membrane oxygenation. our objective was to examine the relative frequencies of bleeding and thromboembolic events and their associations with survival among a cohort of consecutive patients receiving venovenous extracorporeal membrane oxygenation. design: retrospective cohort study. setting: a single academic medical center. patients: adult patients receiving venovenous extracorporeal membrane oxygenation and anticoagulation. eligibility criteria for this analysis were selected to emulate the population that would be recruited for a randomized trial of anticoagulation strategies during venovenous extracorporeal membrane oxygenation. patients were excluded if they had active bleeding or thromboembolism prior to extracorporeal membrane oxygenation initiation, a history of trauma or surgery in the days prior to extracorporeal membrane oxygenation initiation, an arterial extracorporeal membrane oxygenation cannula, or if they received greater than hours of extracorporeal membrane oxygenation support at another institution interventions: none. measurements and main results: outcomes included bleeding and thromboembolic events, duration of extracorporeal membrane oxygenation support, hospital length of stay, and in-hospital survival among patients receiving venovenous extracorporeal membrane oxygenation. bleeding events occurred in patients ( . %), and thromboembolism occurred in eight patients ( . %). bleeding events were associated with longer duration of extracorporeal membrane oxygenation support (p = . ) and worse in-hospital survival (p = . ). thromboembolic events did not appear to be associated with clinical outcomes. conclusions: in this cohort of patients receiving venovenous extracorporeal membrane oxygenation and anticoagulation, bleeding occurred more frequently than thromboembolism and was associated with worse survival. these results highlight the need for randomized trials to evaluate the safety and efficacy of continuous iv anticoagulation among patients receiving venovenous extracorporeal membrane oxygenation. key words: adult; critical care; extracorporeal membrane oxygenation; hemorrhage; respiratory distress syndrome; thromboembolism b leeding and thromboembolism are common during venovenous extracorporeal membrane oxygenation (ecmo) ( ). reported frequencies and associations with clinical outcomes vary and available data are limited by heterogenous study populations ( ) ( ) ( ) . multiple anticoagulation strategies have been proposed to balance the risks of bleeding and thromboembolism during venovenous ecmo ( , ) , but which strategy is most effective remains unknown. data on the relative frequencies of bleeding and thromboembolism during venovenous ecmo, and their respective associations with survival, are needed to provide preliminary data and inform equipoise for future randomized trials. our objective was to evaluate the frequency and clinical significance of bleeding and thromboembolic events during venovenous ecmo. we hypothesized that bleeding events, but not thromboembolic events, would be associated with worse in-hospital survival. we performed a retrospective cohort study examining data from all patients who received venovenous ecmo at the adult hospital at vanderbilt university medical center between january , , and may , . prespecified exclusion criteria were used with the goal of including a patient population similar to those who would be included in a randomized trial comparing anticoagulation strategies, a technique known as "target trial emulation" ( ) . we excluded patients who had active bleeding or thromboembolism prior to ecmo initiation, experienced trauma or surgery in the days prior to ecmo initiation, received greater than hours of ecmo support at another institution, or received arterial cannulation. the study was approved by the vanderbilt university medical center institutional review board (irb no ). we collected the following data from the electronic health record: patient characteristics in the hours prior to ecmo initiation; bleeding and thromboembolic events during venovenous ecmo as previously defined ( ); and clinical outcomes, including in-hospital survival, ecmo duration, and hospital length of stay. bleeding events were defined as overt bleeding associated with either a drop in hemoglobin concentration by g/dl or a transfusion of at least two units of packed rbcs in hours, bleeding at any critical site (e.g. intracranial bleeding), or bleeding requiring a procedural intervention ( ) . thromboembolic events were defined as cerebral stroke, intracardiac thrombus, acute pump head thrombosis, acute oxygenator failure, pulmonary emboli, or deep vein thrombosis (dvt) ( ) . cannula-associated dvts following decannulation did not meet the composite definition for thromboembolic event and were omitted from the survival analysis to limit immortal time bias. continuous variables are presented as median with interquartile range (iqr). categorical variables are summarized as frequencies and percentages. differences between groups were compared using a chi-square test, fisher exact test, or wilcoxon rank-sum test as appropriate. log-rank tests were used to compare time with hospital discharge between groups. all analyses were performed using stata . (statacorp, college station, tx), and a twosided p value of . was considered to be statistically significant. no adjustments were made for multiple testing. of the patients who received venovenous ecmo during the study period, met exclusion criteria. a total of patients were excluded for recent trauma or surgery, patients were excluded for active bleeding, patients were excluded for recent thromboembolism, five patients were excluded for receiving ecmo at an another institution for greater than hours, and three patients were excluded for arterial cannula placement while receiving venovenous ecmo. a total of patients were included in the analysis. the median age was years (iqr, - yr), and % were women. according to institutional protocols, all patients received a continuous infusion of unfractionated heparin following ecmo cannulation, titrated to either antifactor xa levels of . - . u/ml or a partial thromboplastin time of - seconds. a total of bleeding events occurred among patients ( . %), including eight gastrointestinal bleeds, seven intracranial hemorrhages, four cannula site bleeds, four episodes of hemoptysis, three tracheostomy bleeds, two hemothoraces, and two episodes of epistaxis. of these, six ( intracranial hemorrhages and gastrointestinal bleed) were considered the primary cause of death. the median time from ecmo cannulation to first bleeding event was days (iqr, - d). eight patients ( . %) experienced a thromboembolic event during ecmo, including five deep venous thromboses (dvt), two acute circuit thromboses requiring circuit exchange, and one brachial artery thrombosis. the median time from ecmo cannulation to first thromboembolic event was days (iqr, - d). no thromboembolic events were considered the primary cause of death. a total of additional cannula-associated dvts were identified on protocolized ultrasound screening following decannulation. baseline characteristics and serum markers of coagulation and thrombocytopenia were similar between groups ( table ) . anticoagulation monitoring did not vary between groups. rbc transfusion requirement was greater among patients with a bleeding event than patients without a bleeding event (p = . ). in univariate analysis, patients who experienced a bleeding event had a longer duration of ecmo support (p = . ) and worse inhospital survival compared with patients who did not experience a bleeding event (p = . ) ( table and fig. ) . thromboembolic events did not appear to be associated with any differences in duration of ecmo support, hospital length of stay, or in-hospital survival (table and fig. ). in this retrospective cohort study of patients receiving venovenous ecmo for respiratory failure, all of whom received continuous anticoagulation, nearly half of patients experienced a bleeding event. patients who experienced a bleeding event experienced worse survival than patients who did not experience a bleeding event. in contrast, thromboembolic events were less frequent and did not appear to affect survival. this is the first study to examine the relative impact of bleeding or thromboembolism during venovenous ecmo only. these results should prompt further research to evaluate the safety and efficacy of continuous iv anticoagulation in such patients. several factors may contribute to bleeding and thromboembolism in patients receiving ecmo. the interface of blood and nonbiologic circuit components causes activation of the coagulation system and the consumption and degradation of hemostatic factors ( , ) . underlying critical illness compounds the risks of bleeding and thromboembolism ( ) . continuous anticoagulation during ecmo may increase the risk of bleeding ( ), and prior retrospective data suggest a dose-response relationship between anticoagulation and bleeding events ( , ). conducting venovenous ecmo without continuous systemic anticoagulation has been proposed ( , ). although confounded by indication bias, recent observational studies suggest that strategies using only prophylactic doses of anticoagulation appear safe in venovenous ecmo ( , ) . further, a recent systematic review suggested that the rates of thromboembolism and circuit thrombosis among patients who did not receive systemic anticoagulation during venovenous ecmo were comparable with the rates reported among patients treated with systemic anticoagulation ( ) . it is possible that avoidance of systemic anticoagulation might improve outcomes for some patients receiving venovenous ecmo. our study has several strengths. by including only patients without a pre-existing indication or contraindication to anticoagulation, the population in our study emulates the population that would be recruited for a randomized trial of anticoagulation strategies during venovenous ecmo. further, we used previously published, objective criteria to define bleeding and thromboembolism. our study has several limitations. the study was conducted at a single center using a retrospective design. although we used structured and prespecified eligibility criteria, selection bias remains possible. the risks of bleeding and thromboembolism may be confounded by severity of illness and immortal time bias. finally, this study was largely conducted prior to the coronavirus disease (covid- ) pandemic. only one patient in the study cohort experienced respiratory failure as a consequence of covid- . emerging data describe both hypercoagulability ( ) and a higher risk of bleeding for patients receiving venovenous ecmo for covid- ( ) . it is unknown if the results of this analysis would be different if conducted entirely among a population of patients receiving venovenous ecmo for covid- . our data include only patients who received anticoagulation and do not inform the risks of thromboembolism among patients receiving venovenous ecmo without anticoagulation or with prophylactic-dose anticoagulation. this purely descriptive univariate analysis does not attempt to account for potential confounders and does not infer a causal relationship between bleeding or thromboembolism and survival. in this cohort of patients receiving venovenous ecmo and anticoagulation, bleeding occurred more frequently than thromboembolism and was associated with worse survival. these results provide preliminary data for a randomized trial examining the safety and efficacy of systemic anticoagulation in select patients receiving venovenous ecmo. drs. stokes and gannon contributed equally to this work. drs. stokes, gannon, sherrill, bacchetta, rice, semler, and casey contributed to conception and design of the study. drs. stokes, gannon, sherrill, and armistead contributed to data acquisition. drs. stokes, gannon, and sherrill contributed to analysis of the data. drs. stokes and gannon drafted the initial article. all authors contributed to the data interpretation and edited the article for important scientific content. all of the authors agree to be accountable for all aspects of the work in regards to accuracy and integrity. bacchetta was supported, in part, by the national institutes of health (nih) jr chair in surgery no . dr. rice was supported, in part, by the nih (ul rr ). dr. semler was supported, in part, by the national heart, lung, and blood institute (k hl ). dr. casey was supported predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation severe respiratory failure, extracorporeal membrane oxygenation, and intracranial hemorrhage anticoagulation practices during venovenous extracorporeal membrane oxygenation for respiratory failure. a systematic review extracorporeal life support organization: elso anticoagulation guideline low-dose versus therapeutic anticoagulation in patients on extracorporeal membrane oxygenation: a pilot randomized trial using big data to emulate a target trial when a randomized trial is not available clinical controversies in anticoagulation monitoring and antithrombin supplementation for ecmo kaplan-meier in-hospital survival curves from time of venovenous extracorporeal membrane oxygenation for patients who did and did not experience a bleeding event and for patients who did and did not experience a thromboembolic event current understanding of how extracorporeal membrane oxygenators activate haemostasis and other blood components feasibility of veno-venous extracorporeal membrane oxygenation without systemic anticoagulation venovenous extracorporeal membrane oxygenation with prophylactic subcutaneous anticoagulation only: an observational study in more than patients thrombosis and bleeding in extracorporeal membrame oxygenation (ecmo) without anticoagulation: a systematic review covid- : the vasculature unleashed extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with covid- : a retrospective cohort study key: cord- -wid qas authors: le guen, m.; parquin, f. title: place de l’assistance extracorporelle en pathologie respiratoire()() date: - - journal: nan doi: . /j.jeurea. . . sha: doc_id: cord_uid: wid qas extra-corporeal membrane oxygenation (ecmo) effectively replaces the lung in providing oxygenation and carbon dioxide (co( )) removal. for some years, and in parallel to the h n influenza pandemic, this technique has gained interest in relation to significant technological improvements, leading to new concepts of “awake and mobile ecmo” or rehabilitation with ecmo. finally, the publication of randomized controlled trials giving encouraging results in the adult respiratory distress syndrome (ards) has helped to validate this technique and further studies are warranted. this general review aims to outline the definition, classification and principles of ecmo and to give some current information about the indications and possibilities of the technique to the pulmonologist and intensivist. further possible uses for this technique include extra-corporeal removal of co( ) during hypercapnic respiratory failure and assistance during lung transplantation from the preoperative to the early postoperative period. esperanza, tel est le prénom donné par l'équipe soignante à ce nouveau-né, qui en bénéficia de la première fois avec succès d'un échangeur pulmonaire dans le traitement d'une détresse respiratoire néonatale. sa survie inespérée augura les possibilités thérapeutiques offertes par cette technique d'assistance respiratoire extracorporelle. l'oxygénation extracorporelle (extra-corporeal membrane oxygenation, ecmo) désigne à l'origine une technique de suppléance complète de l'échangeur respiratoire (épuration du co couplée à l'oxygénation) et se différencie de la circulation extracorporelle (cec) qui pallie une défaillance cardiaque [ ] . dans les années qui ont suivi ce succès, les développements de cette nouvelle technique « déportée » au lit du patient furent parallèles aux développements technologiques. toutefois, à la fin des années , on observa un arrêt quasi complet de cette technique de suppléance suite à la parution d'un essai thérapeutique chez l'adulte atteint de syndrome de détresse respiratoire aiguë (sdra). en effet, zapol et al. n'ont montré aucune amélioration de la survie des patients sous ecmo comparativement au traitement médical avec ventilation conventionnelle [ ] . même si de nombreuses critiques méthodologiques peuvent être portées à cet essai, il conduisit au quasi-abandon de cette technique chez l'adulte, laquelle fut remplacée par la ventilation oscillométrique à haute fréquence ou encore la ventilation « liquide » totalement abandonnée aujourd'hui. vingt ans plus tard, des améliorations techniques ou des essais cliniques favorables chez des patients en impasse thérapeutique concourent au renouveau de cette technique en réanimation [ ] . deux grandes études à la fin des années vont jouer un rôle déterminant : l'étude cesar en [ ] qui a montré une amélioration significative de la survie en bonne santé à mois des patients bénéficiant de cette technique en cas de sdra sévère. ensuite, l'étude néo-zélandaise et australienne montrant l'intérêt de l'ecmo dans les formes graves avec des taux de mortalité attendus proches de % de sdra lié à la pandémie grippale h n [ , ] . ces résultats ont conduit à un équipement national massif dans l'ensemble des réanimations [ ] . récemment encore, l'atteinte respiratoire liée au coronavirus (mers-cov) a conduit à la mise en oeuvre d'ecmo [ ] . enfin, les progrès technologiques (échangeur, miniaturisation. . .) ont été réalisés dans l'intervalle et ont permis également la réduction significative de la morbidité propre à cette thérapeutique [ ] . dès lors une meilleure connaissance de la technique, de ces dénominations et de sa place dans l'arsenal thérapeutique est nécessaire pour poser justement et sans retard l'indication d'une assistance respiratoire extracorporelle qu'il s'agisse d'optimiser l'oxygénation par technique d'ecmo ou qu'il s'agisse de décarboxylation par épuration extracorporelle du co . l'objectif de cette revue est de dresser le portrait actuel de cette technique encore réservée aux situations les plus graves et les challenges qu'elle pose au pneumologue et au réanimateur aujourd'hui. nous aborderons notamment la place de l'ecmo dans la prise en charge du sdra qui a fait l'objet d'une conférence de consensus nationale très récente [ ] , ainsi que les indications de l'assistance respiratoire extracorporelle (ecmo ou décarboxylation) au cours des décompensations respiratoires terminales hypercapniques et de la transplantation pulmonaire. quelles que soient leur dénomination, il s'agit dans tous les cas de techniques d'assistance reposant sur une circulation extracorporelle qui permet le remplacement temporaire total ou partiel et de la pompe cardiaque et/ou de l'échangeur respiratoire. la cec avec son abord classique intra-thoracique ou central reste largement associée à l'environnement de bloc opératoire (chirurgie cardiaque ou thoracique) et présente pour avantages de pouvoir suppléer complètement le bloc « coeur-poumon » ou de suppléer la pompe cardiaque partiellement. en ce qui concerne les assistances extracorporelles périphériques, elles s'appliquent à deux domaines distincts. le premier est la suppléance partielle et transitoire de la pompe cardiaque dans le cadre de défaillances cardiogéniques (post-chirurgie cardiaque, post-ressuscitation ou post-ischémique) par un double abord veineux et artériel ainsi que des débits de pompes élevés (ecmo veino-artérielle). le second domaine d'application est de pallier une défaillance respiratoire au premier plan via un échangeur à membrane, soit dans le cadre d'une hypoxémie sévère (sdra. . .) avec la mise en oeuvre d'une ecmo veino-artérielle ou veino-veineuse, soit dans le cadre d'une défaillance hypercapnique avec la mise en oeuvre d'une ecmo veino-veineuse ou d'une technique d'épuration extracorporelle de co . dans ce dernier cas, la décarboxylation est l'objectif principal et des débits plus faibles sont nécessaires. ainsi l'ecmo présente comme différence avec la cec : un accès vasculaire périphérique le plus souvent, un volume réduit des circuits et des canules, des faibles besoins en anticoagulants et des débits d'assistance moindres. ces différentes caractéristiques font de l'ecmo un outil « mobile » permettant le transport du patient ou encore sa mobilisation dans le cadre de programme de réhabilitation. par ailleurs, si l'ecmo est particulièrement adaptée au traitement de défaillance respiratoire, elle peut également représenter une technique de suppléance hémodynamique (sdra avec défaillance cardiogénique. . .). le principal déterminant dans ce cas est le débit sanguin. cette différenciation détermine les indications thérapeutiques du système. en effet, un bas débit (par convention entre ml et , l/min) ne peut assurer une oxygénation optimale ni une suppléance cardiaque et sera donc essentiellement une technique de décarboxylation avec ou sans pompe centrifuge. en effet, la production de co pour un individu sain est d'environ ml/min et elle augmente de % en cas de détresse vitale. les propriétés de diffusion élevées du co font que son élimination peut donc être complète pour des débits de l'ordre de ml/min associée à un flux de lavage élevé au travers d'une membrane d'échange [ ] . avec des débits de pompes plus élevés au-delà de l/min et des canules de plus gros diamètre, on peut en plus améliorer l'oxygénation. ces techniques à haut débit permettent de faciliter la mise en oeuvre de stratégies de ventilation protectrice voire, « ultra-protectrice ». si on augmente encore les débits dans le cas d'une assistance veino-artérielle, il devient alors possible d'assurer une suppléance cardiaque gauche en plus des objectifs d'oxygénation et de décarboxylation [ ] . la terminologie de l'ecmo comprend quelques codes pour être comprise de tous et il convient actuellement de préciser (fig. ) . la localisation des canules (veineuse et/ou artérielle) en débutant par le site de prélèvement du sang veineux puis le site de réinjection du sang oxygéné/décarboxylé qui peut être soit veineux (on parle alors d'ecmo veino-veineuse ou v-v) soit artériel (ecmo veino-artérielle ou v-a). ainsi, une ecmo v-a fémoro-fémorale signifie un prélèvement par une canule longue disposée dans la veine fémorale qui draine au mieux l'oreillette droite et une réinjection de sang oxygéné dans l'artère fémorale à contre-courant. par défaut, on considère aujourd'hui que l'ecmo est une technique avec des abords vasculaires exclusivement périphériques, c'est-à-dire avec une canulation en dehors de la cavité thoracique, même si dans de rares cas un abord central est la force motrice génératrice de débit peut être uniquement hydrostatique (système tel que le modèle de type novalung tm ) mais qui est le plus souvent développée par l'utilisation d'une pompe centrifuge non occlusive. le type d'assistance attendue : épuratrice de co uniquement, amélioration de l'oxygénation ou assistance cardiaque partielle ou totale. les quatre constituants principaux d'une ecmo sont les canules (prélèvement et réinjection de sang au patient), l'oxygénateur, la pompe non occlusive et la console de contrôle (fig. ) . les canules existent avec des calibres différents, à adapter à la morphologie du patient pour limiter les risques de thrombose et d'ischémie de membre. elles comportent le plus souvent une armature métallique leur conférant souplesse tout en évitant la survenue de plicature. désormais la plupart des canules sont héparinées, ce qui limite significativement le recours aux anticoagulants en cours de pose et d'entretien. le diamètre de la canule de drainage est le principal déterminant du débit et de l'oxygénation. en cas d'abord de l'artère fémorale, il est actuellement fortement recommandé de mettre en place, malgré l'emploi de canules de petits calibres, un cathéter artériel de reperfusion du membre inférieur pour limiter la survenue d'ischémie de membre secondaire. récemment est apparue sur le marché une canule double lumière pour une pose en jugulaire : canule avalon tm [ ] . elle possède un canal de prélèvement avec des orifices situés à l'extrémité distale dans le territoire cave inférieur et un canal de réinjection en auriculaire. la plus grosse série observationnelle démontre une efficacité très satisfaisante en épuration du co tout en étant grevée d'une morbidité faible [ ] . elle permet donc d'envisager une pose chez un patient vigile bénéficiant d'un programme de réhabilitation en attente d'une transplantation par exemple [ ] . ces canules sont reliées aux autres éléments constitutifs de l'ecmo par le circuit à proprement parler : celui-ci, le plus court possible, est constitué également de tuyaux pré-héparinés le plus souvent (fig. ) . le second constituant majeur est l'oxygénateur, le plus souvent en polyméthyl-pentène, membrane fortement perméable aux gaz. il permet par une surface d'échange considérable (entre et m sur un principe proche de la dialyse rénale) d'épurer le co présent en veineux par un gradient de pression transmembranaire favorisé par un balayage constant de cette membrane en oxygène. par ailleurs, selon le même principe, il permet d'oxygéner le sang veineux admis à l'entrée. la présence d'un flux laminaire réduit l'activation plaquettaire et la formation d'embols. la durée de vie de la membrane est maintenant prolongée avec les nouvelles générations. le troisième élément qui a bénéficié d'apports technologiques novateurs est la pompe rotative centrifuge, constituée d'un rotor mobile. cette pompe est facultative en cas de systèmes à bas débits à fonctionnement exclusivement hydrostatique (novalung tm ) [ ] . elle présente comme caractéristique d'être une pompe non occlusive (contrairement à la pompe utilisée en cec) qui comprend deux disques de diamètres différents tournant à des vitesses différentes et provoquant par cette occasion un effet vortex à l'origine du débit. comme toute pompe non occlusive, son fonctionnement dépend directement de la précharge et de la postcharge. en outre, une moindre activation des facteurs de la coagulation en l'absence d'application d'un stress cellulaire répété (occlusion du circuit) est obtenue. l'ensemble de ces éléments rend possible le transport du patient ou sa mobilisation dans le cadre de procédures de réhabilitations pré-ou postopératoire. le dernier élément est la console de commande et de surveillance. elle permet de régler en particulier le nombre de tours/minutes générés par la pompe et ainsi de prescrire le débit de pompe. dans certains cas, la mesure des pressions d'entrée et de sortie sont relevées. au total, le débit d'ecmo va dépendre des pressions d'amont et d'aval, du calibre des canules et du nombre de tours/minute de la pompe. il est possible d'ajouter au circuit d'ecmo un réchauffeur pour limiter la survenue d'hypothermie. ceci se discute surtout pour les ecmo à haut débit avec un risque majoré de déperdition thermique par convection et lorsque la durée d'assistance est non connue. en pratique, la mise en place d'une ecmo se fait par un abord percutané selon la méthode de seldinger (repérage vasculaire via une aiguille, puis maintien d'un guide métallique pour la montée des canules). dans certaines situations comme l'obésité ou les techniques veino-artérielles, une technique combinée seldinger et abord direct du scarpa ou de la région axillaire est nécessaire pour une meilleure visualisation des vaisseaux. cette étape est le plus souvent dévolue aux chirurgiens, plus compétents dans la gestion d'une complication décrite dans près de % des cas (dissection, traumatisme vasculaire), même si certaines équipes de réanimation ont acquis ces dernières années une vraie expertise. par ailleurs, se sont développées en parallèle les équipes mobiles de pose d'ecmo qui sont disponibles à tout moment, se déplacent sur des sites extérieurs et assurent le transfert inter-hospitalier de ces patients. ce type de structure va probablement se généraliser dans les années à venir en labellisant des centres de références et des équipes mobiles spécialisées dans la pose et les transferts. la préparation du circuit d'ecmo est sous la responsabilité d'un médecin ou infirmier perfusionniste, et le maintien nécessite un référent qui peut assurer localement la surveillance et la formation à cette technique des personnels de réanimation ou de bloc opératoire. la position des canules, plus particulièrement l'extrémité de la canule de prélèvement, est vérifiée au mieux par l'échographie trans-oesophagienne en cas de pose sous anesthésie générale ou sous amplificateur de brillance car elle permet de visualiser directement le flux sanguin de la canule de réadministration et d'optimiser son placement. quel que soit l'abord (fémoral ou jugulaire), l'orifice sera positionné en territoire cave inférieur avec un passage transauriculaire dans le second cas ou à l'abouchement auriculaire droit [ ] . la réalisation d'une radiographie pulmonaire en fin de procédure reste indispensable même si seule la partie armée des canules est visualisée, ce qui ne correspond pas exactement à l'extrémité distale des canules. l'échographie cardiaque permet également d'optimiser le débit de la pompe, permettant une préservation minimale de la circulation pulmonaire en cas de transplantation pulmonaire. l'une des limites de l'ecmo veino-veineuse est la possibilité de recirculation, c'est-à-dire qu'une partie du sang prélevé correspond à du sang artérialisé qui vient d'être réinjecté [ ] . pour limiter cet effet, il convient de maintenir une certaine distance entre les deux sites, évaluée par certains à cm. en cas de canulation artérielle fémorale, il convient de réaliser les gazométries artérielles au niveau de l'artère radiale droite [ ] . en effet, la réinjection de sang artérialisé se fait de manière rétrograde, ce qui a pour conséquence un mélange de sang très oxygéné par la membrane avec le sang peu oxygéné venant du coeur. les prélèvements au membre supérieur droit seront donc le reflet de ce mélange de sang et permettront d'estimer l'oxygénation cérébrale en cas de polygone de willis imparfaitement efficace. une oxygénation satisfaisante à la gazométrie assure la présence de sang oxygéné jusqu'à l'artère sous-clavière droite et donc dans l'ensemble des troncs supra-aortiques. en cas de canulation dans l'artère axillaire ou sous-clavière, cette problématique se pose peu puisque la réinjection intervient dans le sens du flux sanguin antérograde, en amont des troncs supra-aortiques. au maximum, en cas de débit cardiaque largement supérieur au débit de pompe, on observera un syndrome dit d'arlequin (bas du corps « rouge » et portion céphalique « bleue ») [ ] (fig. ) . par ailleurs, ce flux rétrograde peut occasionner une augmentation de la postcharge. en cas de dysfonction myocardique préalable (sepsis. . .), elle peut aboutir à un oedème pulmonaire par dysfonction du ventricule gauche, voire dans certaine situation à une dilatation aiguë du ventricule gauche nécessitant une « décharge » urgente (fig. ) . ces éléments font préférer à la technique veino-artérielle la technique veino-veineuse, par une canule de prélèvement dont l'extrémité se situe en territoire cave inférieur proche de l'oreillette droite ( - cm) et une réinjection le plus proche de l'oreillette droite ou en territoire cave supérieur avec la possibilité de débits d'assistance élevés (jusque - l/min) adaptés aux objectifs thérapeutiques : ecmo v-v fémoro-jugulaire interne, utilisée dans le sdra. la surveillance d'un patient sous ecmo comporte un certain nombre de spécificités et doit être formalisée par l'utilisation de checklists. si la surveillance hémodynamique, souvent invasive dans ces situations, ne présente pas de particularité, il convient de surveiller la saturation artérielle (membre supérieur droit en cas d'ecmo v-a fémoro-fémorale), la température corporelle et la perfusion du membre inférieur canulé si c'est le cas (chaleur, pouls pédieux doppler, aspect cutané). une surveillance spécifique des sites d'insertion à la recherche de complications locales comme les hématomes, les saignements est nécessaire, ainsi que la recherche de signes cliniques d'hémolyse. d'un point de vue paraclinique, la gazométrie artérielle reste l'élément de surveillance principal tandis que la mesure de la saturation veineuse en o sur le circuit en amont de la membrane semble le monitorage minimal de l'ecmo. il permet de s'assurer d'un apport d'oxygène minimal au tissu et une chute brutale de la valeur doit alerter sur la survenue d'une complication (hémorragie, défaillance cardiogénique, sepsis. . .) ou sur la constitution d'une hypovolémie [ ] . enfin, la surveillance de l'ensemble du circuit d'ecmo requiert une certaine expertise et du personnel formé pour éviter tout retard diagnostique. on vérifiera l'absence de plicature du circuit, l'absence de balancement rythmique des tubulures signant une éventuelle hypovolémie, l'absence de baisse du débit non prescrit, l'absence de thrombus dans le circuit et sur la membrane d'oxygénation. la mesure des pressions d'entrée et de sortie, tout comme sur les appareils d'hémofiltration, est un outil complémentaire utile pour la détection rapide d'anomalie au sein du circuit ou chez le patient. les réglages reposent sur la vitesse de balayage du circuit (débitmètre en l/min) fonction de la paco , la fraction délivrée en oxygène selon l'hypoxémie du patient et enfin le débit de pompe selon le niveau d'assistance ou de shunt à contrecarrer. une étude récente comparant différents régimes d'ecmo (variation de débit, de fio ) a pu préciser les paramètres d'optimisation de l'assistance [ ] . ainsi, il apparaît que l'anémie doit être corrigée et avec des seuils de transfusion élevés pour un hématocrite > % (cesar) ou une hémoglobinémie > g/dl [ ] . comme précisé dans la définition, l'ecmo est une technique de suppléance transitoire et l'objectif est donc le retrait dès que la fonction respiratoire s'améliore, le plus souvent avant le sevrage de la ventilation mécanique. aujourd'hui, plusieurs techniques visent à déterminer le moment optimal de l'ablation mais les principes restent les mêmes : diminution progressive du débit de balayage, puis du débit de pompe et de la fraction délivrée en oxygène de l'ecmo, en mesurant régulièrement les capacités de l'échangeur du patient par des gazométries répétées. en cas d'assistance veinoartérielle, cette décroissance du débit s'accompagnera d'échographie cardiaque afin d'évaluer parallèlement la fonction myocardique. puis un test de sevrage est réalisé avant l'ablation complète [ ] , le plus souvent précédant le sevrage. [ ] . enfin, la décision en cas de défaillance respiratoire primaire chez un patient sous ventilation mécanique doit intervenir le plus tôt possible après l'échec d'optimisation de la ventilation conventionnelle, comprenant notamment le recours au décubitus ventral si balance bénéfice/risque de cette technique le permet. par conséquent, la pose d'une indication d'ecmo est le plus généralement collégiale impliquant les réanimateurs, les pneumologues en cas de pathologies respiratoires (tableau ). les situations pour lesquelles le recours à l'ecmo constitue une balance défavorable sont la présence de lésions intracrâniennes hémorragiques ou potentiellement hémorragiques, les comas post-anoxiques, les sdra avec une ventilation mécanique préalable prolongée et la préexistence d'un sepsis ou d'une immunosuppression sévère. la défaillance hypoxémique et plus particulièrement le syndrome de détresse respiratoire aiguë (sdra) constitue la principale indication de l'ecmo et a été le moteur du développement récent de cette technique [ ] . la plupart des études reposent sur les critères de définition du sdra de , lesquels viennent d'être modifiés selon la conférence de berlin pour proposer trois niveaux de gravité de sdra : mineur, modéré et majeur [ ] . les premiers succès d'assistance extracorporelle ont été décrits en néonatologie dans le traitement des détresses respiratoires par inhalation de méconium puis quelques séries sont parues chez l'adulte en proposant cette technique en sauvetage [ ] . ceci a conduit à la publication de l'étude clinique princeps (cesar), qui a en particulier réhabilité l'ecmo chez l'adulte dans le sdra, est parue en dans le lancet [ ] . elle faisait suite à la publication de résultats sur des séries de patients avec des résultats encourageants [ ] et visait à comparer chez des patients en réanimation atteints de sdra le traitement conventionnel (ventilation protectrice) [ ] et la mise en oeuvre d'une ecmo veino-veineuse (fig. ) . les patients au total étaient sévèrement atteints dans chaque groupe et les résultats ont montré un avantage de cette nouvelle technique, puisque % des patients ont survécu à mois avec une bonne autonomie comparativement à % dans le groupe témoin (p = , ). ces résultats positifs étaient par ailleurs associés à des critères de tolérance satisfaisants puisqu'aucun accident hémorragique, en particulier cérébral, n'a été relevé [ ] . la même année dans l'hémisphère sud, la pandémie de grippe issue de la souche influenza a (h n ) à l'origine de sdra très sévères a conduit nombre d'équipes à la pose d'ecmo chez ces patients. ainsi deux études prospectives observationnelles depuis la nouvelle-zélande et l'australie [ , ] ont montré des résultats encourageants avec plus des deux tiers des patients survivant dans le groupe ecmo alors que l'indication était souvent une thérapeutique de sauvetage devant une mortalité attendue proche de %. toutefois, les thérapeutiques (ecmo ou traitement conventionnel) n'étaient pas randomisées, ce qui limite la portée des conclusions [ , ] . ces différentes études ont permis également d'envisager dans cette indication une ecmo veino-veineuse le plus souvent fémoro-jugulaire, voire avec une canule coaxiale double lumière [ ] . en effet, cet abord ne provoque pas de majoration de la postcharge cardiaque gauche (potentiellement défaillant sur myocardiopathie septique) et permet une mise au repos du poumon lésé (ventilation protectrice) en assurant une décarboxylation efficace [ ] . par ailleurs, le profil de tolérance est largement supérieur en l'absence de complication grave comme la description récente de perforation myocardique [ , ] (tableau ). la même année en france, les services de réanimation ont bénéficié d'un équipement large en ecmo [ ] . un registre national a été établi sous l'égide du groupe reva (réseau européen de recherche en ventilation artificielle). en analyse multivariée réalisée à partir d'un groupe de patients traités par ecmo, les facteurs de risque associés à la mortalité en réanimation étaient l'âge, le niveau de lactates à j de l'ecmo, une pression de plateau plus élevée [ ] . l'étude preserve (predicting death for severe ards ou vv-ecmo) a proposé récemment un score tenant en particulier compte de huit facteurs dont le statut d'immunocompétence, l'origine infectieuse et les paramètres ventilatoires pour mieux sélectionner les indications [ ] . une autre piste prometteuse dans le traitement du sdra est le recours à une ventilation hyperprotectrice utilisant des volumes courants de ml/kg environ associée à une décarboxylation par un système d'assistance extracorporelle à bas débit en vue de réduire les atteintes pulmonaires induites par la ventilation [ ] . aujourd'hui, dans le sdra majeur [ ] , un accord global préconise donc une ecmo veino-veineuse à haut débit ( - l/min) en cas d'hypoxémie majeure (rapport pao /fio < mmhg sous fio = ) pendant au moins heures et réfractaire à une ventilation protectrice optimisée (pression de plateau < cmh o, paco < mmhg) comportant notamment le décubitus ventral [ ] . par ailleurs, la réflexion sur cette stratégie peut s'envisager dans une situation où un patient présente un rapport pao /fio < mmhg pendant heures et/ou une acidose respiratoire avec un ph < , (conférence de consensus sdra) [ ] . des réflexions pour proposer cette technique en cas d'atteinte de la mécanique respiratoire avec l'existence de pressions de plateau élevées sont en cours. par ailleurs, le recours à l'ecmo au sein de centres de référence est également régulièrement mis en avant [ ] . comme la ventilation non invasive à ses débuts, l'ecmo veino-veineuse a d'abord démontré son efficacité en cas de défaillance hypercanique aiguë sévère. les premiers pas ont été réalisés par pesenti avec une assistance bas-débit à visée d'épuration de co exclusive chez un patient emphysémateux bulleux responsable de pneumothorax bilatéraux récidivant [ ] . le développement a suivi avec l'équipe italienne de ranieri qui a montré que l'épuration du co par assistance extracorporelle en cas d'acidose hypercapnique sévère permettait une ventilation ultra-protectrice (volume courant inférieur à ml/kg) avec nette réduction des marqueurs de l'inflammation [ ] . dès lors, le champ de l'exacerbation du patient atteint de bronchopneumopathie chronique obstructive (bpco) s'ouvre. cette thérapeutique est d'autant plus aisée à concevoir qu'elle est possible désormais avec l'utilisation d'une seule canule veineuse à double lumière disposée par voie percutanée en jugulaire interne [ ] . une étude pilote a ainsi montré que l'ecmo veino-veineuse par canule unique double lumière avait permis d'éviter l'intubation chez des patients bpco en exacerbation aiguë et qu'elle avait même permis de sevrer de la ventilation non invasive un autre groupe de patient totalement dépendant [ ] . aussi, la réflexion est-elle aujourd'hui de préciser les critères de décision tels qu'une décompensation respiratoire hypercapnique réversible (facteurs déclenchant connus) afin de ne retarder ni la pose d'une ecmo éventuelle, ni la mise sous ventilation mécanique et de démontrer l'impact de cette technique sur la mortalité de ces patients. dans ce contexte, les canules double lumière coaxiales présentent comme points d'amélioration : un meilleur repérage de la localisation des orifices de drainage et de réinjection, et une amélioration de leur souplesse pour limiter le risque de plaie myocardique [ ] . À ce titre, un essai randomisé multicentrique est en cours (essai decopd-extracorporeal co removal in copd exacerbation : nct ). par ailleurs, un nouveau dispositif d'épuration du co exclusif dérivé des techniques d'épuration rénale vient d'obtenir le marquage ce en france. il possède comme particularités : un circuit interne réduit, une membrane d'échange très performante, une canule ou cathéter souple et une mesure précise de l'épuration du co : système hemolung ® [ ] . les principaux écueils de cette technique restent la nécessité d'une surveillance continue en soins intensifs et la compétence nécessaire de l'équipe en charge. dans le cas de défaillance hypercapnique non réversible chez des patients très sélectionnés, l'ecmo pourrait être proposée comme technique de suppléance, à condition d'une réversibilité attendue de l'exacerbation clinique ou d'un plan thérapeutique. cette réflexion est nouvelle et doit faire l'objet d'études complémentaires bien conduites. une place particulière concerne les cas d'embolie pulmonaire massive. en effet, une publication récente démontre l'intérêt de cette technique, notamment en cas d'arrêt cardiaque [ ] . ainsi, les auteurs rapportent à propos de arrêts cardiaques sur embolie pulmonaire massive une récupération circulatoire pour l'ensemble des patients sous ecmo veino-artérielle posée rapidement, moyennant une complication hémorragique dans % (fibrinolyse). dix d'entre eux ont survécu, sept avec un bon pronostic neurologique. cet article compare par ailleurs la qualité de survie à des ecmo posées dans le cas d'infarctus du myocarde étendu et montre un pronostic plus favorable dans le cadre de l'embolie pulmonaire grave [ ] . ces résultats sont confortés par une étude récente [ ] . l'asthme aigu grave peut aussi constituer une indication de sauvetage [ , ] . l'ecmo assure une oxygénation minimale, une épuration efficace du co et surtout permet une ventilation protectrice du poumon en limitant sans difficulté les pressions de crête et de plateau. une seule étude historique sur un collectif de enfants et adolescents existe. elle a montré une survie dans % des cas avec des indices de sévérité majeure lors de la prise en charge : médiane de paco = mmhg ( - ). le délai de maintien de la technique est globalement supérieur à jours [ ] . • l'ecmo veino-veineuse, le plus souvent fémorojugulaire, est une technique de suppléance efficace en cas de sdra sévère ou de décompensation respiratoire sur le mode d'une acidose hypercapnique. • en l'absence de défaillance cardiaque, l'utilisation d'une canule double lumière veino-veineuse disposée en territoire jugulaire est une stratégie envisageable. • l'efficacité de la technique pour décarboxyler le sang du patient tant en bas qu'à haut débit permet de mettre en place des stratégies de ventilation protectrice, voire hyperprotectrice. • d'autres indications pneumologiques peuvent être discutées telles que l'embolie pulmonaire massive, l'asthme aigu grave. en transplantation pulmonaire, l'ecmo est assez largement utilisée depuis quelques années. on distingue trois situations bien distinctes : le bridge à la transplantation, l'ecmo peropératoire et l'ecmo postopératoire pour la prise en charge des défaillances primaires du greffon les plus graves. l'objectif de ce chapitre est de présenter brièvement les éléments de la littérature et l'expérience des auteurs. il n'existe pas de consensus établi actuellement. la place de l'ecmo dans cette indication et surtout les conditions de mise en oeuvre ont beaucoup évolué récemment avec l'introduction du concept d'ecmo vigile [ , ] . les patients concernés sont des candidats inscrits sur la liste nationale d'attente de transplantation ou connus des centres de transplantation qui présentent une décompensation de leur insuffisance respiratoire terminale ne pouvant être améliorée par d'autres traitements tels que la ventilation non invasive ou l'oxygénothérapie à hauts débits en cas d'hypoxie prédominante. l'objectif est de les amener à la transplantation dans les meilleures conditions en évitant toute défaillance extra-respiratoire. le concept d'ecmo vigile repose sur l'absence de sédation, une extubation rapide, la mise en oeuvre d'une stratégie de réhabilitation associant une kinésithérapie motrice et respiratoire intensives, une renutrition par voie digestive. les séries publiées d'ecmo en bridge à la transplantation pulmonaire sont de petite taille ( à patients) le plus souvent monocentriques [ ] [ ] [ ] avec une transplantation pulmonaire réalisée dans et % des cas [ ] . la survie à an est comprise entre et %. À ce jour, seule une étude rétrospective conduite par fuehner a comparé le devenir d'un groupe ecmo vigile de patients avec un groupe historique de patients intubés-ventilés [ ] . au total, % des patients ont été transplantés dans le groupe ecmo vigile contre % dans le groupe ventilation mécanique (non statistiquement significatif). la durée de ventilation mécanique postopératoire était significativement réduite dans le groupe ecmo vigile, de même la survie à mois était meilleure ( vs %, p = , ). par ailleurs, crotti et al. ont montré que le pronostic de ces patients était corrélé à la durée d'ecmo pré-transplantation [ ] : % pour une durée d'ecmo inférieure à jours contre % au-delà. les meilleures indications actuelles semblent être les défaillances respiratoires à dominance hypercapnique. c'est le cas des patients atteints de mucoviscidose en exacerbation très sévère dépendants de la ventilation non invasive évoluant vers l'épuisement ventilatoire. on privilégie alors une ecmo veino-veineuse, si possible sur canule jugulaire unique à double courant. dès la fin de la procédure, le patient est réveillé, si possible extubé. il sera alors possible de débuter très rapidement la réhabilitation respiratoire puis motrice (mobilisation au lit, mise au fauteuil et reprise de la marche). parallèlement, le patient peut être nourri per os et/ou par sonde d'alimentation [ ] . en cas d'extubation difficile, le recours à une trachéotomie peut s'avérer nécessaire. pour atteindre cet objectif d'ecmo vigile, une équipe médicale soignante et des kinésithérapeutes entraînés sont indispensables. dans les autres pathologies avec ou sans défaillance cardiaque associée (fibrose pulmonaire, hypertension artérielle pulmonaire primitive), la stratégie d'ecmo vigile est possible mais de réalisation plus complexe [ , ] . en france, cette situation de bridge ouvre l'accès depuis à l'inscription en super-urgence et donc à une priorité. pour obtenir de bons résultats et les améliorer, il faut respecter les deux points suivants : • la survenue de complications, en particulier d'autres défaillances que respiratoires, un saignement non contrôlé, une détérioration de l'état nutritionnel à l'origine de complications cutanées contre-indiquent le plus souvent définitivement le recours à la transplantation pulmonaire et rendent même futile la poursuite de l'ecmo. en cas de sepsis respiratoire, celui-ci devra être contrôlé avant l'inscription en super-urgence ; • ces procédures d'ecmo, en particulier vigile, nécessitent d'être réalisées par des équipes médicales, paramédicales et kinés formées et entraînées aux spécificités de cette prise en charge et à la prévention des complications. en peropératoire, l'ecmo a quasi remplacé la cec conventionnelle en transplantation mono-ou bipulmonaire. elle a permis de diminuer les besoins transfusionnels et les complications postopératoires [ ] . une autre utilisation de l'ecmo de développement récent concerne la « réhabilitation » pulmonaire du poumon du donneur par technique dite ex vivo [ ] . les résultats encourageants des équipes canadienne et scandinave a conduit à un protocole d'utilisation en france validé par l'agence de biomédecine. les défaillances primaires du greffon les plus sévères constituent l'indication principale de l'ecmo postopératoire. elles surviennent le plus souvent dès la fin de l'intervention, se manifestent par un oedème pulmonaire majeur, des opacités pulmonaires bilatérales et une altération des gaz du sang avec des rapports p/f inférieurs à mmhg malgré l'optimisation de la ventilation mécanique, et souvent une défaillance cardiaque associée. elles sont essentiellement liées à des phénomènes d'ischémie-reperfusion. dans ce cas, l'ecmo sera plutôt veino-artérielle fémoro-fémorale. il existe en effet souvent une part de défaillance cardiaque associée. le débit d'ecmo sera fixé autour de à % du débit cardiaque pour limiter le temps d'ischémie chaude du greffon. les débits de gaz doivent permettre une ventilation protectrice comme dans la prise en charge des sdra classiques. les anticoagulants sont utilisés à faible dose, voire introduits à la e heure, vu le risque élevé de saignement. l'évolution est souvent favorable en quelques jours, permettant le sevrage et le retrait de l'ecmo. certaines équipes telles celle de vienne ont montré l'intérêt de poursuivre l'ecmo v-a en postopératoire pendant quelques heures pour prévenir et limiter le développement de défaillance respiratoire sévère en cas de situation jugée à haut risque [ ] . en cas de pose d'ecmo postopératoire, la survie avoisine % à un an [ , ] et diminue encore lorsque l'ecmo est instituée à distance de la transplantation [ ] , en particulier en cas de tableau infectieux ou de pneumopathie [ ] . toutefois, ces séries portent sur de petits nombres de patients ou couvrent de grandes périodes prenant mal en compte l'évolution des pratiques péri-opératoires et les progrès techniques des assistances. • l'ecmo en bridge pré-transplantation permet une réhabilitation préopératoire chez un patient vigile avec des résultats initiaux encourageants. • l'ecmo tend actuellement à remplacer la cec dans ses indications peropératoires en transplantation uni-ou bipulmonaire. • en postopératoire, la décision de pose d'ecmo doit intervenir rapidement pour réduire la morbimortalité des défaillances primaires du greffon les plus graves. l'ecmo a repris un nouvel essor depuis quelques années avec des résultats encourageants dans un bon nombre d'indications. la connaissance de cette thérapeutique par le pneumologue est essentielle car elle peut aujourd'hui se discuter pour différentes atteintes respiratoires aiguës. les progrès techniques font même espérer le développement d'une véritable assistance respiratoire de longue durée à l'instar de l'assistance cardiaque. dans ce cadre, la réalisation d'études multicentriques complémentaires et la tenue de registres nationaux devraient permettre de préciser les indications de l'ecmo vv dans le sdra. les auteurs déclarent ne pas avoir de conflits d'intérêts en relation avec cet article. prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome) extracorporeal membrane oxygenation in severe acute respiratory failure. a randomized prospective study extracorporeal life support for severe acute respiratory distress syndrome in adults cesar trial collaboration. efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for influenza a(h n ) acute respiratory distress syndrome critical care services and h n influenza in australia and new zealand extracorporeal membrane oxygenation for severe influenza a (h n ) acute respiratory distress syndrome: a prospective observational comparative study transmission and evolution of the middle 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in awake patients as bridge to lung transplantation organ allocation waiting time during extracorporeal bridge to lung transplant affects outcomes active rehabilitation and physical therapy during extracorporeal membrane oxygenation while awaiting lung transplantation: a practical approach experience of extracorporeal membrane oxygenation as a bridge to lung transplantation in france bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device lung transplantation on cardiopulmonary support: venoarterial extracorporeal membrane oxygenation outperformed cardiopulmonary bypass ecmo et transplantation pulmonaire foch lung transplant group. techniques and results of lobar lung transplantations normothermic ex vivo lung perfusion in clinical lung transplantation institutional experience with extracorporeal membrane oxygenation in lung transplantation extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the extracorporeal life support organization (elso) registry early institution of extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation improves outcome extended use of extracorporeal membrane oxygenation after lung transplantation key: cord- -niy bgg authors: dai, qing-qing; liu, yan; ren, yu-dong; yu, kai-jiang; wang, hong-liang title: clinical efficacy of extracorporeal membrane oxygenation in cardiogenic shock patients: a multi-center study date: - - journal: chin med j (engl) doi: . /cm . sha: doc_id: cord_uid: niy bgg nan the design is a multi-center cross-sectional study with the aim to assess the clinical therapeutic efficacy of ecmo and investigate the influence on key parameters. all the cs patients who received ecmo from six hospitals in china from january to january were selected (n = ) as ecmo group, and the control group of cs patients were randomly selected from all the patients who also developed cs in the same period and received conventional therapy. however, due to the fact that five patients in control group abandoned the treatment after initiating treatment, those patients were excluded in the final analysis (n = in the control group). the study was conducted in accordance with the ethical guidelines of the declaration of helsinki. the study was also approved by the ethics committee of the second affiliated hospital of harbin medical university (no. -research- ) and all subjects signed written informed consent. in ecmo group, all the patients received standard ecmo treatment. the patients in control group received conventional treatment including inotropes, diuresis, coronary artery dilation, heart preload, and afterload improvement. meanwhile, intra-aortic balloon pump counterpulsation, blood purification, or mechanical ventilation was also applied when necessary in both groups. all statistical analyses were performed using statistical analysis system (sas) (version . . , sas institute inc., cary, nc, usa). spearman rank correlation coefficient was used to analyze the correlation of acute physiologic assessment and chronic health evaluation ii (apache ii) score with survival and survival time. logistic regression analysis was used to analyze the influence of treatment, age, gender, and apache ii score on survival time. the dynamic changes of variables were analyzed by running repeated measures analysis of variance (anova). a p < . was considered as statistically significant. the results showed that the baseline data were not statistically different between the two groups. however, acute physiology and chronic health evaluation ii (apache ii) score in ecmo group was higher than that of control group (z = . , p = . ), suggesting that the ecmo patients were more severe than the control patients. the mortality rate was / ( . %) in ecmo group and / ( . %) in control group. however, the mortality rates and survival time were not statistically different between two groups. in addition, apache ii score in the non-survivors in ecmo group was higher than non-survivors in control group (t = . , p = . ). in non-survivors, spearman rank correlation analysis showed that apache ii score was negatively correlated with survival time (r s = À . , p = . ), indicating that higher apache ii score was correlated with shorter survival time. multivariant logistic regression analysis of risk factors for survival time of non-survivors showed that only apache ii score was statistically significant (odds ratio = . ; % confidence interval . - . ; p = . ), suggesting that higher apache ii score was a risk factor for shorter survival time. it indirectly suggested that the clinical efficacy of ecmo treatment was better compared to the conventional treatment of control group. from clinical experience, ecmo has a great significance in improving systemic circulation and providing gas exchange, which has also been supported in other studies. [ ] repeated measures anova showed that the dynamic changes of mean arterial pressure (map), central venous pressure (cvp) and pao /fio and creatinine were significantly different between ecmo group and control group. the improvement on map, pao /fio , and cvp demonstrated that ecmo was more effective than the conventional treatment. the baseline of creatinine in ecmo group was higher than that of control group (p < . ). however, the ecmo did not show significant improvement on creatinine. the reason might be that there was already severe kidney dysfunction so it was hard to restore the kidney function even when the perfusion was improved [ figure a -d]. heart rate (hr), map, central venous oxygen saturation (scvo ), and hemoglobin (hb) were significantly different between non-survivors and survivors in ecmo group. hb level can be easily affected by transfusion history. thus, we did not focus on hb in the discussion. the generalized linear model for repeated measurement analysis of hr, map, and scvo showed that the outcome of ecmo patients could be estimated based on those factors. in other words, if the factors were not improved within the st day, the patient was most probably not going to survive [ figure e -h]. in conclusion, ecmo can improve the survival of cs patients compared with conventional therapy. the dynamic change of map, pao /fio , and cvp demon-strated that ecmo was more effective than the conventional treatment. the dynamic changes of hr, map, and scvo have certain guiding significance to assess the clinical efficacy and evaluate the prognosis after ecmo application. the work was supported by grants from the coronavirus disease outbreak special project of from heilongjiang provincial association for science and technology innovation: research on coping strategies of coronavirus disease on the platform of critical medicine and international medical exchange foundation of china (no. z- (no. z- - - . the percutaneous ventricular assist device in severe refractory cardiogenic shock intra-aortic balloon pump counterpulsation (iabp) for myocardial infarction complicated by cardiogenic shock extracorporeal membrane oxygenation support for incessant tachyarrhythmia-induced severe cardiogenic shock extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis survival analysis after extracorporeal membrane oxygenation in critically ill adults: a nationwide cohort study clinical efficacy of extracorporeal membrane oxygenation in cardiogenic shock patients: a multi-center study figure : the generalized linear mode for repeated measurement analysis of different parameters of extracorporeal membrane oxygenation and control groups (n = ) b) central venous pressure pao /fio ; (d) creatinine; (e) heart rate (hr) f) mean arterial pressure (map); (g) scvo ; (h) hemoglobin (hb) none. key: cord- -ja b vy authors: waterer, g. w.; wunderink, r. g. title: adjunctive and supportive measures for community-acquired pneumonia date: - - journal: infectious diseases in critical care doi: . / - - - - _ sha: doc_id: cord_uid: ja b vy the widespread introduction of penicillin in the s resulted in a substantial reduction in mortality from community-acquired pneumonia (cap). however, despite significant advances in medical science, only a small improvement has occurred since, particularly in patients with bacteremic pneumococcal pneumonia [ , ]. even modern intensive care has only made a small difference to the mortality in patients with severe pneumonia [ , ]. while the aging population, increased number of patients with severe co-morbid illnesses, and the human immunodeficiency virus (hiv) epidemic have certainly contributed to the persistently high mortality rate [ , , ], apparently healthy, immunocompetent patients continue to die from cap. disturbingly, a recent british thoracic society study concluded that no available therapy could substantially reduce the mortality rate from severe cap in young adults [ ]. the widespread introduction of penicillin in the s resulted in a substantial reduction in mortality from community-acquired pneumonia (cap). however, despite significant advances in medical science, only a small improvement has occurred since, particularly in patients with bacteremic pneumococcal pneumonia [ , ] . even modern intensive care has only made a small difference to the mortality in patients with severe pneumonia [ , ] . while the aging population, increased number of patients with severe co-morbid illnesses, and the human immunodeficiency virus (hiv) epidemic have certainly contributed to the persistently high mortality rate [ , , ] , apparently healthy, immunocompetent patients continue to die from cap. disturbingly, a recent british thoracic society study concluded that no available therapy could substantially reduce the mortality rate from severe cap in young adults [ ] . while some causative microorganisms, such as pseudomonas, and some strains of common causative microorganisms appear to be more virulent, the majority of cap patients who die are infected with organisms sensitive to commonly prescribed antibiotics. even the recent emergence of high level penicillin-resistant strains of s. pneumoniae has not significantly increased the mortality of cap. given that most cap patients die despite microbiological confirmation that they received appropriate antibiotic therapy, the introduction of new antibiotic classes is unlikely to reduce mortality further. for this reason, research has been directed into non-antibiotic therapeutic measures. generally, supportive measures for cap can be separated into two categories -( ) immunomodulatory therapy for the systemic inflammatory response induced by pneumonia and ( ) support for the gas exchange abnormalities unique to a pulmonary source of sepsis. chapter focuses on potential immunomodulatory therapies in patients with sepsis, including pneumonia. this chapter will focus on a few pneumoniaspecific immunomodulatory therapies and other advances in the intensive care management of patients with severe cap. although discussed in chapter , a more detailed discussion of the recent controversy over high dose corticosteroids in patients with cap is warranted. the best evidence of benefit for corticosteroids comes from studies in specific, narrowly defined groups of cap patients caused by less common agents. randomized, controlled trials have shown corticosteroids reduce mortality in aids patients with pneumocystis carinii pneumonia and significant hypoxia, if instituted at or prior to the onset of anti-pneumocystis therapy [ , ] . based on a small, retrospective study of subjects, corticosteroids may also improve the outcome of severe varicella pneumonia [ ] . anecdotally, corticosteroids are frequently used in the setting of severe fungal pneumonia, particularly due to histoplasmosis [ , ] , and a small controlled trial of patients supported their use in miliary tuberculosis [ ] . following the success of pre-antibiotic corticosteroids in children with meningitis [ ] , marik and colleagues [ ] studied the effect of a single dose of hydrocortisone ( mg/kg) min prior to antibiotic therapy in a small randomized placebo controlled trial of adult patients with severe cap (scap). hydrocortisone had no detectable effect on tumor necrosis factor alpha (tnf) production in the following h, mortality (only four deaths) or length of stay in the icu. while not encouraging, the small number of subjects studied ( received hydrocortisone), the use of only a single dose and the measurement of only a single pro-inflammatory cytokine for only h does not qualify this study to be a definitive statement on the role of corticosteroids in cap. an important finding of this study was that beta-lactam antibiotics did not result in a significant increase in serum tnf levels, as rapid antigen release due to bacterial lysis has been postulated as a potential cause of deterioration in patients with severe cap [ ] . also supporting a possible role for corticosteroids in severe cap, montón and co-workers [ ] studied the effect of intravenous methylprednisolone on bronchoalveolar lavage fluid (balf) and serum cytokines in patients with severe nosocomial pneumonia or cap. the patients who received methylprednisolone had significantly lower serum and balf tnf, interleukin (il)- q , il- and c-reactive protein. there was also a non-significant trend to lower mortality in the steroid treated group ( % vs. %). recently, confalonieri and colleagues compared intravenous hydrocortisone ( mg bolus followed by mg/h for days) with placebo in patients with severe cap admitted to the icu [ ] . the trial was stopped early after an interim analysis showed a significant mortality benefit in the steroid group ( % vs %, p = . ). however, the mortality difference was driven by deaths after day and a high incidence of "delayed septic shock". the marked incidence of this scenario has not been seen in any other scap study. significant differences in the percent of patients who received noninvasive ventilation rather than intubation and mechanical ventilation also compromise the data regarding a beneficial effect of steroids on gas exchange. noninvasive ventilation has been shown by the same group to decrease mortality compared to invasive ventilation [ ] . the statistical design of the study led to an early closure of the study, limiting the ability to exclude the possibility that other factors explain the mortality difference. the complete absence of any mortality in the corticosteroid group has also raised significant concerns about potential bias in patient selection and whether either the control or case cohort were truly representative of the general group of patients with severe cap. despite the reservations, all three pilot studies suggested a trend toward benefit with steroids so further clinical studies clearly need to be conducted. prostaglandin antagonists are worth special comment as they have been studied in animal and human patients with pneumonia. ibuprofen reduced the intrapulmonary shunt fraction from % to % in dogs with lobar pneumonia [ ] , with a corresponding decrease in the consolidated area of lung. acetylsalicylic acid had a similar effect, reducing the shunt fraction from % to % [ ] . the mechanism is unclear but may be due to reversal of prostaglandin inhibition of the hypoxia-induced pulmonary vasoconstriction. in a small study of ten subjects with pneumonia requiring mechanical ventilation, hanley et al. [ ] studied the effect of indomethacin ( mg/kg oral or rectal) on arterial oxygenation. five subjects had substantial improvement in oxygenation with a small improvement in three additional patients. improvement tended to occur in the patients with the greatest degree of hypoxemia. as ibuprofen administration appears to be relatively safe, even in the setting of sepsis [ ] , further studies are warranted. in contrast, ferrer et al. found a g infusion of acetylsalicylic acid (asa) had no effect on arterial oxygenation in seven patients with severe unilateral pneumonia [ ] . although intrapulmonary shunting did reduce by a small amount ( ± % vs. . ± %), the lack of clinically apparent benefit was discouraging. several possible explanations were advanced to explain the discrepancy between this study and that of hanley et al. clearly, a difference in efficacy between asa and indomethacin may be the cause. however, the subjects in the study by hanley et al. were also more severely hypoxic, with a mean pa /fi of compared to . in any event, it would seem reasonable for future studies to use indomethacin in preference to asa. before the advent of antibiotic therapy, passive immunization with serum was used with some success in patients with pneumonia [ ] . mortality was reduced by approximately % in most age groups with a diminishing effect in patients over the age of . with the exception of patients with specific immunoglobulin deficiencies, this therapy has largely been abandoned due to the much greater efficacy of antibiotics in addition to the difficulty, and cost, of obtaining sufficient serum. the development of new antiviral drugs has also largely obviated the anecdotal use of hyper-immune serum in cytomegalovirus and varicella pneumonitis. while the overall efficacy of pneumococcal immunization is unclear, especially in the elderly with some comorbid illnesses, several studies and a meta-analysis have suggested that even if pneumococcal pneumonia is not prevented, the incidence of invasive pneumococcal disease is decreased. the use of specific anti-pseudomonal exotoxin antibodies has been tried as an adjunct to antibiotics with some success in mice [ ] and guinea pigs [ ] , and pseudomonas specific vaccines have enhanced antibiotic response in guinea pigs [ ] . anti-pseudomonal antibodies appeared safe in human subjects with evidence of increased opsonophagocytic activity in a small phase i study of subjects [ ] , but further studies are required to determine whether they have any clinically relevant effect. in human sepsis studies, generic anti-endotoxin strategies have so far been disappointing [ , ] . although they have not specifically been studied in pneumonia, the primary site of sepsis in many of the patients in these studies was the lung, indicating a low likelihood of benefit. legionella pneumophila is consistently identified as a leading cause of cap, particularly in patients with severe cap [ - ] . unlike pneumococcal pneumonia, the immune response to legionella infection is predominantly of a th type [ ] and bacterial killing is predominantly by macrophages [ ] . skerrett and martin studied the effect of interferon gamma (ifn * ), a potent stimulator of macrophage function [ , ] , given as an intratracheal bolus in rats with experimental l. pneumophila pneumonia [ ] . intratracheal ifn * markedly reduced the replication of l. pneumophila in corticosteroid treated rats, but had no detectable effect in immunocompetent rats or when given intraperitoneally. the ability to give ifn * by aerosol is particularly appealing since not only are systemic side effects avoided, but also a much greater effect on intrapulmonary macrophage function is seen compared to systemic administration [ ] . aerosolized ifn * has also been shown to be safe in patients with drug resistant tuberculosis [ ] , and may have a role in treatment of this condition. further studies of nebulized ifn * , especially in patients with pulmonary legionellosis, are awaited. after many unsuccessful trials of non-antibiotic agents designed to disrupt or ameliorate the pro-inflammatory process driving septic shock and associated organ failure, activated protein c (drotrecogin alpha activated) was the first successful agent to reduce mortality in a large randomized, double blind, placebo controlled trial [ ] . while -day mortality was clearly better in sub-groups of patients who received drotrecogin alpha activated [ ] , the subgroup with community-acquired pneumonia drove most of the benefit of the drug [ ] , with the greatest reduction in mortality seen with streptococcus pneumoniae infection (rr= . ; % ci . - . ). the availability of rapid urinary antigen detection for s. pneumoniae allows this association to enter clinical decision-making (several references for urinary antigen). drotrecogin alpha activated appeared to have a greater effect in single organ failure than waiting for multiple ( & two) organ failure but clearly has its greatest benefit in patients who have the highest acuity of illness. worsening thrombocytopenia, suggestive of early disseminated intravascular coagulation, appears to be another important indicator for patients likely to respond to drotrecogin alpha activated [ ] . while different criteria for the administration of drotrecogin alpha activated have been established in different institutions around the world, the presence of pneumonia and shock should prompt physicians to consider its use as early as is possible. the main additional supportive therapy unique to cap is improved oxygenation and secretion clearance. the remainder of supportive care is not different than that of other critically ill patients with infection. cap is one of the more common causes of severe hypoxic respiratory failure. a common method to improve oxygenation, the addition of positive end expiratory pressure, may actually make oxygenation worse in patients with severe asymmetrical lung disease like cap. the peep will tend to overdistend the unaffected lung, increasing pulmonary vascular resistance on the local area. this overdistension may then direct greater blood flow to the pneumonic area, especially if hypoxic vasoconstriction has been blocked by some bacterial product. with extensive unilateral pneumonia, positioning the ventilated patient in the lateral decubitus position with the affected lung up has been demonstrated to improve oxygenation [ ] . positioning increases perfusion to the dependent, non-involved lung, increases secretion clearance from the affected lung, and may allow addition of peep without increasing shunt because the dependent lung is now less compliant and less likely to become overdistended. the combination of positioning and prostaglandin inhibitors is usually adequate to temporarily improve oxygenation until hypoxic vasoconstriction is restored. differentially ventilating each lung by means of a dual lumen endotracheal tube may also be beneficial [ , ] . this allows the use of higher levels of peep in the affected, less compliant, lung and lower levels of peep in the normal lung, thus reducing the risk of barotrauma. a study by ranieri et al. showing a correlation between the level of peep and pro-inflammatory cytokine production further supports this approach to protect the 'normal' lung [ ] . the point at which differential ventilation is worth commencing is not clear, but carlon and colleagues [ ] suggest optimal benefit occurs when there is a ml or greater difference in distribution of tidal volume between each lung. ecmo, a modification of cardiopulmonary bypass, was designed to provide oxygenation in patients with severe respiratory failure. although available since the s, initial poor results from a national institutes of health sponsored prospective, multicenter randomized trial [ ] limited the use of ecmo to research centers. however, a significant reduction in complications has led to resurgence in interest in ecmo as a means of providing oxygenation when all other means have failed. the role of ecmo has most extensively been studied in neonates. in newborn infants with respiratory failure unresponsive to other therapy it has proven highly effective, having an overall survival of % in over , neonates where nearly % mortality would be expected [ ] . modification of the neonatal ecmo technique has also been effective in some pediatric patients with respiratory failure [ ] , including those with pneumonia from both bacterial [ ] and viral [ ] pathogens. as would be expected, as the duration of ecmo required increases, the prognosis decreases [ ] . in the nih-sponsored ecmo trial, adults with viral pneumonia did particularly poorly. in a retrospective review of adults with severe acute respiratory failure supported with ecmo by kolla and colleagues [ ] , a % survival rate was found in the patients with a primary diagnosis of pneumonia. although this mortality seems high, patients selected for ecmo had an expected mortality in excess of %. predictors of poor response to ecmo were increasing age, days of ventilation prior to commencement of ecmo and the degree of respiratory failure as measured by the pa /fi ratio. cases of successful intervention in adults with severe legionella [ , ] , pneumococcal [ ] and varicella pneumonia [ ] have all been reported. the clearest indication for ecmo in adults may be the hantavirus pulmonary syndrome (hps). with no effective antiviral therapy, care is entirely supportive. in a small series, the dramatic but time-limited cardiovascular and pulmonary hemorrhagic manifestations of hps appeared to be well supported by ecmo [ ] . ecmo would appear to have a role in some patients with severe respiratory failure secondary to pneumonia. the timing, duration and patient selection for what is an expensive, labor intensive therapy remain to be determined by prospective studies. liquid ventilation with volatile hydrocarbons has been studied in the management of ards. little data is currently published on its use specifically in human sub-jects with pneumonia. in rats given lethal doses of pneumococci, partial liquid ventilation in combination with perfluorocarbon doubled survival compared to antibiotics alone [ ] . nitric oxide (no) inhalation has also been studied as adjunctive therapy of ards, as well as some other forms of severe pulmonary hypertension. while no studies specifically address human patients with pneumonia, in dogs with escherichia coli pneumonia, inhaled no had a minimal effect on oxygenation and no effect on sepsis induced pulmonary hypertension [ ] . since no is one of the effector molecules released by macrophages to kill bacteria [ ] , inhaled no has a potential antibacterial effect. hoehn and colleagues studied the bacteriostatic effect of no on bacterial cultures from neonates [ ] . at ppm (greater than the usual dose range of - ppm) no inhibited the growth group b streptococcus, staphylococcus epidermidis and e. coli but not pseudomonas aeruginosa or staphylococcus aureus. further studies will be required to determine whether inhaled no has any real bacteriostatic effect in vivo, particularly as it may have deleterious effects on the function of neutrophils [ ] . aerosolized prostacyclin has also been shown by walmrath et al. to improve oxygenation by reducing shunt and pulmonary hypertension in patients with pneumonia [ ] . twelve patients with severe pneumonia (pa /fi < ), six of whom had interstitial lung disease (ild), received varying doses of prostacyclin. patients with ild required substantially larger doses of prostacyclin to produce a clinical effect. although its efficacy has not been compared to no in patients with pneumonia, its greater cost is a significant disadvantage. significant accumulation of mucopurulent secretions can occur in cap, particularly in patients on mechanical ventilation. mucus impaction can lead to obstruction, ranging in severity from linear atelectasis to lobar collapse. clearly the most effective secretion clearance is a spontaneous cough. however, the respiratory compromise often attendant to severe cap may prevent an effective cough. support with noninvasive ventilation (niv) may benefit the patient by both improving respiratory mechanics while allowing the patient to spontaneously expectorate [ ] . however, retained secretions is also one of the causes of failure of niv. an important strategy to avoid this complication is to avoid continuous ap-plication of niv and actively encourage the patient to cough during periods off niv. in mechanically ventilated cap patients, removal of secretions by regular suctioning is essential. the use of percussion or vibration in ventilated patients has been associated with worsening of gas exchange and the benefit in cap patients in general is unclear. the benefit of bronchoscopy for secretion removal is also poorly supported. bronchoscopy for secretion removal has been associated with an increased risk of development of subsequent nosocomial pneumonia [ ] . therefore its therapeutic use should be limited. one of the few studies on this area has suggested that if lobar atelectasis is accompanied by an air bronchogram, bronchoscopy is unlikely to find a mucus plug or benefit the patient. changing the rheologic properties of thick tenacious mucus is often attempted with little scientific support. avoidance of dessication and inspissation of secretions does appear to be important. adequate hydration may be the most effective therapy. intubated cap patients with significant secretions are poor candidates for heat and moisture exchangers and should usually have ventilation initiated with heated humidification. the pharmacologic intervention most often ordered is n-acetylcysteine. most support for this therapy is an extension of results in some cystic fibrosis patients. whether the same benefit can be achieved in cap patients is unclear as there is no published data of n-acetylcysteine use in this setting. the potential benefit is also partially offset by induction of bronchial irritation and bronchospasm in some patients. preliminary data on agents with more physiologic support, such as utp [ ] , are encouraging but need further study. guaifenesin has limited data in non-pneumonia patients and is unlikely to have a major benefit in intubated cap patients. although a variety of other mucolytic agents are available, including bromhexine, rhdnase and polymyxin b, there is no data to support their use in patients with pneumonia. cap remains a significant health problem and patients continue to die despite receiving appropriate antibiotic therapy. modification of the host immune response, both anti-and pro-inflammatory approaches, has yet to live up to the promise of improved outcome. despite this, there is significant reason for optimism. some immunomodulatory therapies clearly have efficacy in some patients. as our understanding of the immune response to pneumonia 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complications associated with veno-arterial extra-corporeal membrane oxygenation: a comprehensive review date: - - journal: crit care doi: . /s - - -z sha: doc_id: cord_uid: eutz xy veno-arterial extracorporeal membrane oxygenation (va-ecmo) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. among its potential complications, va-ecmo may adversely affect lung function through various pathophysiological mechanisms. the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. also, va-ecmo increases the afterload of the left ventricle (lv) through reverse flow within the thoracic aorta, resulting in increased lv filling pressure and pulmonary congestion. furthermore, va-ecmo may result in long-standing pulmonary hypoxia, due to partial shunting of the pulmonary circulation and to reduced pulsatile blood flow within the bronchial circulation. ultimately, these different abnormalities may result in a state of persisting lung inflammation and fibrotic changes with concomitant functional impairment, which may compromise weaning from va-ecmo and could possibly result in long-term lung dysfunction. this review presents the mechanisms of lung damage and dysfunction under va-ecmo and discusses potential strategies to prevent and treat such alterations. veno-arterial extracorporeal membrane oxygenation (va-ecmo) is a life-saving technology providing respiratory and circulatory support in patients with refractory cardiogenic shock or cardiac arrest [ ] and which may give time to plan future therapeutic decisions such as the insertion of long-term cardiac assist devices or heart transplantation (htx) [ ] . notwithstanding its potential benefits, va-ecmo remains associated with significant morbidity and mortality [ ] . this is partly due to the patients' critical condition, but also to complications related to va-ecmo, notably renal failure, sepsis, bleeding, thromboembolism, limb ischemia, and multiorgan failure [ , ] . va-ecmo-induced pulmonary complications are much less recognized, except from the pulmonary congestion related to left ventricle pressure overload induced by retrograde va-ecmo flow within the thoracic aorta [ ] . beside this particular aspect, several additional mechanisms may contribute to lung damage and dysfunction in the setting of va-ecmo. the latter may be assimilated to a simplified cardiopulmonary bypass (cpb) circuit, and both techniques share common pitfalls with respect to lung physiology. cpb may alter pulmonary function after cardiac surgery by promoting an inflammatory response via biomaterial-dependent and biomaterial-independent factors, the collapse of lungs during the procedure, the shunting of pulmonary circulation, and the phenomenon of lung reperfusion injury which takes place once cpb is weaned [ ] . during va-ecmo, although such processes are attenuated, they still occur at different stages of support and at various degrees, and they may persist for days or weeks. in such conditions, the combination of a chronic inflammatory response, pulmonary congestion, and lung ischemia could foster a wealth of morphological and functional alterations which could interfere with patient's recovery and compromise the overall planned therapeutic strategy. in this review, we discuss the pathophysiological mechanisms and potential clinical implications of the pulmonary complications associated with va-ecmo. the induction of a systemic inflammatory response syndrome (sirs) by the contact of blood with biomaterial is a typical consequence of extracorporeal circulation [ ] . while extensively studied in the field of cpb, this is also witnessed during va-ecmo, as recently reviewed [ ] . in addition, patients undergoing va-ecmo are critically ill and suffer from profound cardiogenic shock, which by themselves contribute to the development of sirs [ ] . the lung is a major target of inflammatory injury in the context of sirs, owing to its extensive capillary bed and the presence of abundant immune cells within the lung parenchyma. therefore, the occurrence of sirs in the context of ecmo provides a highly favorable environment for the development of acute lung injury [ , ] . the main mechanisms triggering the inflammatory response to biomaterials are presented below. blood contact with va-ecmo circuitry activates the contact system (cs) and the complement system ( fig. ) . cs generates kallikrein [ ] , which activates monocytes fig. main va-ecmo-induced mechanisms of lung damage and dysfunction. left side: sirs is initiated by the blood contact with the circuitry surface. it activates humoral cascades, platelets, and leukocytes, leading eventually to ec injury and activated pmn sequestration into the lung parenchyma. right side: ec injury favors fluid infiltration into both alveolar space and lung parenchyma, leading to pulmonary edema, which is aggravated by the increase of pulmonary vein pressure. alveolar edema and decreased pulmonary artery perfusion lead to lung parenchymal ischemia which in turn maintains chronic inflammation and promotes neoangiogenesis and fibrosis generation and polymorphonuclear cells (pmns), and triggers the intrinsic coagulation cascade, resulting in the rapid generation of thrombin and fibrin within the systemic circulation [ ] . thrombin activates platelets and endothelial cells (ecs) and induces the secretion of pro-inflammatory mediators and growth factors, such as interleukin- (il- ), interleukin- (il- ), or platelet-derived growth factor (pdgf) [ ] . the extrinsic coagulation pathway is activated to a lesser extent, mainly through the release of tissue factor (tf) by activated monocytes and ecs. cs also generates bradykinine [ ] , which activates ecs and leukocytes, and elicits hemodynamic alterations including systemic vasodilation and pulmonary vasoconstriction [ ] . complement activation occurs via the alternative pathway, generating the anaphylatoxins c a and c a, which activate ecs. c a is also a potent mediator of leukocyte chemotaxis. a peak of complement activation occurs within - h of ecmo onset, followed by a progressive decreases over the next to days [ ] . the humoral response triggered by blood-biomaterial interaction comprises the release of multiple cytokines [ ] . whereas a balance between pro-and anti-inflammatory cytokines is reached several hours after va-ecmo initiation [ ] , an initial imbalance in favor of pro-inflammatory tnf-α, il- β, and il- leads to the activation of ecs and promotes the release of multiple inflammatory proteins by the liver such as fibrinogen, complement, and c-reactive protein. tnf-α plays a major role in the amplification of the early inflammatory response, by upregulating proinflammatory cytokines and prostaglandin synthesis, activating pmns and ecs, and stimulating reactive oxygen species (ros) production [ , ] . platelets are activated by contact with the tubing surface and by thrombin and complement. activated platelets foster the generation of pro-inflammatory cytokines, thromboxane a (txa ), platelet-activating factor (paf), pselectin, and serotonin. txa induces ecs activation and local vasoconstriction, while serotonin and p-selectin promote pmn-endothelial interactions [ ] . platelet activation is maximal at the initiation of va-ecmo and progressively decreases over hours to days but remains persistent [ ] . ec activation leads to their detachment from the basal membrane and disassembly of tight junctions, increasing vascular permeability with the development of sub-endothelial edema [ ] . moreover, activated ecs display an upregulated expression of adhesion molecules favoring pmn adhesion and transendothelial migration [ ] , and they also release cytokines, tissue factor, and ros. circulating pmns, monocytes, and macrophages are spontaneously activated by tubing surfaces [ ] . furthermore, pmns are activated by complement, histamine, serotonin, and paf, which facilitate their adhesion to ecs, diapedesis, tissue infiltration [ ] , and the release of cytotoxic mediators, including proteases, cytokines, and ros. at variance with cpb, va-ecmo is generally maintained over several days. the initial significant sirs gradually decreases [ , ] , mostly through the progressive build-up of counter-regulatory mechanisms leading to compensatory anti-inflammatory response and of possible biomaterial inactivation [ ] . still, a delayed persisting inflammatory response can be observed several days after va-ecmo implementation, whose underlying mechanisms may involve the presence of low concentration of endotoxin within the circulation, which may sustain complement activation, cytokine release, and ros generation, to elicit a sepsis-like inflammation [ , ] . the low-level inflammatory response induced by pulmonary low flow is another potential mechanism (see below). some potential therapies have been proposed to downregulate inflammation and possibly improve lung outcome in this setting. the replacement of a silicon oxygenator by a poly-methyl pentene oxygenator has been associated with reduced radiological signs of pulmonary inflammation on chest x-ray [ ] , while the administration of steroids in patients undergoing va-ecmo has been associated with shortened mechanical ventilation time, although without any survival benefit [ ] . pathophysiology peripheral (femoro-femoral) va-ecmo provides a non-physiological blood flow promoting significant hemodynamic perturbations (fig. ). the retrograde reinjection of blood into the thoracic aorta increases lv afterload and impedes aortic valve opening, while increasing myocardial oxygen demand [ ] . in the setting of cardiogenic shock, these disturbances may worsen lv performance and dramatically reduce lv stroke volume [ , ] . in addition, if lv residual function is insufficient to permit aortic valve opening, progressive lv distension will occur, due to persisting venous return through pulmonary and bronchial veins into the left atrium and through thebesian veins into the lv, with concomitant increase of lv end-diastolic pressure. at worst, stagnation of blood within dilated left cardiac chambers may favor the formation of clots and induce pulmonary vein thrombosis [ ] . pulmonary congestion develops consecutively to the passive upstream transmission of elevated lv pressure [ ] . lung extravascular water accumulation is potentiated by the increased vascular permeability in the context of va-ecmo-induced sirs. the magnitude of afterload increase, lv distension, and pulmonary congestion is dependent on several parameters, including va-ecmo flow, systemic vascular resistance, and lv residual function [ , ] . pulmonary congestion may jeopardize lung parenchymal cell oxygenation through two mechanisms. firstly, interstitial edema increases the thickness of the alveolarcapillary barrier, hence the diffusion distance for oxygen between alveoli and parenchymal cells, whose oxygenation primarily depends on oxygen diffusing from alveolar spaces [ ] . secondly, alveolar edema results in a marked reduction of local alveolar po (pao ). alveolar epithelial cells, normally exposed to pao above mmhg, are sensitive to hypoxia from pao below mmhg, which may occur in alveoli flooded by pulmonary edema [ ] . alveolar hypoxia can destabilize intercellular junctions, impair barrier permeability, impede alveolar fluid clearance and surfactant production by pneumocytes, induce local vasoconstriction and neoangiogenesis, and finally trigger local and systemic inflammation [ ] [ ] [ ] . therefore, pulmonary congestion during va-ecmo creates a vicious circle in which va-ecmoinduced sirs and lv pressure overload promote pulmonary edema, leading to alveolar hypoxia which maintains sirs [ ] . alveolar hemorrhages are another frequent consequence of the combination of pulmonary congestion and the requirement of anticoagulation during ecls. even if massive hemoptysis is rare [ ] , local alveolar hemorrhages are frequent and sustain local inflammatory changes [ , ] . chest x-ray is the simplest exam to assess pulmonary congestion, although its interpretation is complicated by frequently associated abnormalities, such as pneumonia, atelectasis, or alveolar hemorrhages. chest ultrasound is an effective and reliable alternative method to assess interstitial edema, pleural effusion, and parenchymal consolidation [ ] . echocardiographic examination is mandatory, as it may show left heart dilation and indirect signs of cardiac congestion, such as spontaneous contrast echoes or the presence of "sludge" in heart chambers, as well as the absence of aortic valve opening [ ] . hemodynamic monitoring using pulmonary artery catheter (pac) has been associated with improved survival in cardiogenic shock [ ] , notably in the context of mechanical cardiac support. pac is particularly helpful to identify patients with cardiac distension, by demonstrating elevated left-sided filling pressure [ ] . it has been shown that combining a value of pulmonary artery diastolic pressure > mmhg (as a surrogate of pulmonary capillary wedge pressure) with evidence of pulmonary edema on chest x-ray could identify patients with subclinical lv distension [ ] . although these data need further validation, pac is now advocated by most experts to help manage patients under va-ecmo [ ] . severe pulmonary congestion during va-ecmo is associated with a dismal prognosis, and its treatment is mandatory [ , ] . inotropic agents increase cardiac contractility, promote aortic valve opening, and reduce lv dilation and filling pressure. reducing va-ecmo flow to decrease lv afterload, as long as residual lv ejection is present and peripheral perfusion maintained, should also be considered. the insertion of an intra-aortic balloon pump (iapb) is a further option to decrease lv afterload. as demonstrated by bréchot et al., iabp in combination with va-ecmo versus va-ecmo alone is independently associated with less frequent hydrostatic pulmonary edema and a shorter duration of mechanical ventilation [ ] . a recent meta-analysis found concomitant iabp to reduce in-hospital death and length of stay [ ] . if previous steps fail to reduce pulmonary edema, the left heart chambers must be directly unloaded ("vented"), either by percutaneous atrial transseptal approach or by using a venting cannula inserted into the left atrium or the lv apex by surgical or trans-aortic approach [ ] . in addition, the catheter-mounted microaxial pump impella® (abiomed, danvers, ma) may represent a further efficient device to permit lv unloading [ ] . eliet et al. have recently observed that impella® not only decreases lv diastolic diameter but also increases pulmonary flow [ ] . these different modalities of cardiac unloading during va-ecmo have been the matter of several extensive recent reviews [ , ] . the lung is characterized by a dual circulation, comprising the pulmonary circulation, which supplies the alveoli for gas exchange, and the bronchial circulation, which conveys oxygen and nutrients to the airways, but not alveoli, whose oxygen supply is almost exclusively provided by direct diffusion from the alveolar spaces [ ] . bronchopulmonary anastomoses allow collateralization between these two circulations. in case of chronic decrease of pulmonary blood flow (e.g., in chronic thromboembolic disease or pulmonary stenosis), the bronchial flow may increase from to % of the cardiac output, permitting to compensate this decrease and participate to gas exchange, providing a kind of "rescue flow" to the ischemic areas [ , ] . as depicted in fig. , venous blood during va-ecmo is derived from the vena cava and the right atrium through the venous canula, resulting in a reduction of right ventricle (rv) filling, pulmonary blood flow, and pulmonary arterial pulsatility [ ] . in a porcine model, vardi et al. demonstrated that the pulmonary capillary blood flow decreases dramatically as the va-ecmo flow increases [ ] . moreover, in case of pulmonary congestion (see above), the upstream transmission of increased left atrial pressure reduces the transpulmonary perfusion gradient. ventilation with high positive end-expiratory pressure (peep) might also impede pulmonary blood flow by compression of alveolar vessels [ ] . several additional mechanisms, including alveolar hypoxia, reduction of local no production, and the actions of inflammatory mediators can promote vasoconstriction and the subsequent increase of pulmonary vascular resistance, with a reduction of pulmonary blood flow [ ] . it is also noteworthy that blood flow through the bronchial arteries (bas) is also reduced during va-ecmo, due to attenuated pulsatility of the systemic circulation (which supplies the bas). this can further limit blood supply to ischemic areas within the congested lung [ ] . eventually, these various hemodynamic changes may lead to hypoperfusion of the entire pulmonary vasculature, which, superimposed to alveolar hypoxia, can promote a state of global, persistent lung ischemia. the best way to overcome such alterations is, of course, the withdrawal of va-ecmo. if this is not possible, va-ecmo flow may be reduced to maintain partial pulmonary perfusion. in early experimental studies in pigs, prolonged ( h) ecmo at full support (with no residual pulmonary blood flow) promoted massive pulmonary parenchymal damage [ ] , which was not observed at a residual pulmonary blood flow reaching % of the systemic cardiac output [ ] . an additional strategy relies in the upgrading of va-ecmo to a hybrid system of veno-veno-arterial support, with an additional cannula inserted into the jugular vein, which provides oxygenated blood within the pulmonary arteries. this approach is sometimes used to treat the harlequin syndrome (see below), but has not yet been evaluated to prevent lung injury during va-ecmo. although no dedicated study has specifically focused on pulmonary histological consequences of va-ecmo, data from animal models and small human necropsy series have reported several pathological alterations. koul et al. maintained pigs under total cpb for h before weaning. all the animals died within the next h, and on histological examination, more than % of the pulmonary parenchyma displayed edema, hyaline membranes, alveolar hemorrhages, thrombi, and focal necrotic changes [ ] . in another experimental study exploring the effects of long-term va-ecmo without anticoagulation, mizuno et al. succeeded to maintain a goat up to months under va-ecmo with a pulmonary blood flow reduced to %. at autopsy, diffuse interstitial fibrosis and swelling of endothelial cells with thickening of their basal membrane were noted [ ] . in humans, ratliff et al. reported postmortem findings in patients undergoing va-ecmo for to days. in two patients, diffuse lung fibrosis was noted, together with liquefaction necrosis of the lower lobes. the authors hypothesized that the combination of an increase in metabolically active cell mass together with partial pulmonary shunting concurred to establish ischemic areas with subsequent necrosis [ ] . in an autopsy series of infants supported by va-ecmo, chou et al. reported hyaline membrane formation, interstitial and intra-alveolar hemorrhages, and reactive hyperplasia of epithelial and smooth muscle cells, developing already after to days of va-ecmo support, whereas interstitial fibrosis was noted beyond days [ ] . to sum up, va-ecmo appears mostly associated with signs of protein-rich edema, alveolar hemorrhages, tissue necrosis, and fibrosis, which are reminiscent of the damage noted in the acute respiratory distress syndrome. these changes are likely the result of the combination of inflammatory injury, pulmonary congestion, and hypoxia, with the progressive development of epithelialendothelial injury, increased vascular permeability, and interstitial collagen deposition [ ] . furthermore, some degree of angiogenesis and vascular remodeling may also play some role, as alveolar hypoxia and chronic ischemia (typical of long-lasting va-ecmo) can activate several pro-angiogenic cascades in alveolar cells, relying on the hypoxia-inducible factor family or the resistin-like molecule-α [ ] . such alterations could result in longterm changes in pulmonary vascular physiology, with possible detrimental consequences on the right ventricle. pulmonary dysfunction during va-ecmo the impaired pulmonary function induced by va-ecmo may require long-lasting mechanical ventilation (mv) which may further alter the lung through ventilatorinduced lung injury (vili). although there is presently no consensus regarding optimal ventilator settings for mv during va-ecmo, the principles of lung-protective ventilation should be applied [ ] . furthermore, prolonged mv increases the risk of ventilator-associated pneumonia (vap), which occurs in up to % of patients under ecmo, as recently reviewed [ ] , with risk factors including an age > years, a higher sofa score on admission, and a history of copd or hypertension [ ] . causative microorganisms comprise primarily gram-negative bacilli, with pseudomonas aeruginosa isolated in - % of cases [ ] . diagnosis of vap may be particularly troublesome, as the usual criteria of vap are difficult to interpret in the setting of ecmo, and a high clinical index of suspicion coupled to early microbiological sampling are major clues to diagnosis [ ] . treatment of vap on ecmo is challenging, notably because of the alterations of antibiotic pharmacokinetics occurring in this setting, and frequent therapeutic drug monitoring is therefore recommended [ ] . preventive measures to reduce the risk of vap include primarily the reduction of mv duration. in this regard, a strategy of early extubation and awake ecmo support is emerging as a promising strategy [ ] . in properly selected patients, such strategy not only significantly reduces the incidence of vap [ ] , but also permits active mobilization, reduces the overall rate of complications, and increases survival [ ] . the prototypical consequence of va-ecmodependent impairment of lung function is the development of the "harlequin syndrome," reflecting the opposing flows from the heart (antegrade, poorly oxygenated blood flow) and from the peripheral ecmo (retrograde, highly oxygenated blood flow), resulting in differential hypoxia (upper body hypoxemia, lower body normo/ hyperoxemia). the level of mixing of the two flows within the aorta is termed the "watershed," which can be identified in contrast-enhanced ct scan of the chest (fig. ) . the harlequin syndrome may be treated by increasing va-ecmo flow or adding a venous injection cannula either as a hybrid ecmo (veno-veno-arterial ecmo, fig. ) or as pure veno-venous ecmo if the function of the heart allows withdrawal of the arterial cannula. another option consists of switching the arterial cannulation site from femoral to axillary or central (aorta) location, in order to avoid the retrograde flow from the peripheral femoral cannula [ ] . finally, bronchoscopy with bronchial hygiene may be considered routinely in order to maximize chances of successful weaning from va-ecmo when cardiac function recovers [ ] . pulmonary dysfunction after weaning from va-ecmo va-ecmo-induced lung alterations may only appear after weaning and the restoration of physiological pulmonary artery blood flow. in a series of patients who underwent long-term mechanical assist device implantation under va-ecmo (l-vad, bi-vad, or total artificial heart), boulate et al. noticed that % of patients develop acute lung injury (ali) few hours after restoration of pulmonary blood flow, with a significant impact on mortality. the authors hypothesized that chronic lung ischemia during va-ecmo support could promote alveolar frailty and that the sudden restoration of an antegrade pulsatile pulmonary blood flow creates a massive pulmonary bed overload responsible of ali [ ] . accordingly, one of the identified risk factors of ali in this study was the occurrence of a pulmonary edema during the week preceding the implantation of the mechanical device, featuring a preexisting lung frailty. this form of ali is reminiscent of reperfusion pulmonary edema, a well-known and described condition that occurs after reperfusion of a chronic low pulmonary blood flow situation, as in correction of tetralogy of fallot [ ] or pulmonary endarteriectomy for chronic embolism [ ] . such reperfusion pulmonary edema relies both on ischemia-induced chronic inflammation and reperfusion injury that involves similar mechanisms than those described above [ ] . fig. the watershed. a axial. b sagittal. contrast in the aorta indicates blood flow from the va-ecmo arterial cannula, whereas absence of contrast within the ascending aorta indicates blood flow from the native heart. the level of blood mixing in the thoracic aorta represents the va-ecmo watershed (arrows) in order to help the decision-making process in patients under va-ecmo, chen et al. developed a risk factorcalling score (rfss) to select patients eligible for l-vad or htx. the rfss has items and points, of which are allocated to pulmonary dysfunction. a rfss > predicted a poor outcome, which emphasizes the relative burden of pulmonary dysfunction in the outcome of patients under va-ecmo in a bridge strategy [ ] . it is currently unknown whether lung damage and dysfunction induced by va-ecmo have an impact on long-term outcome, the more so that many unrelated factors may interfere with such outcome, such as prolonged icu stay, previous health condition, or reduced lv ejection fraction. a few studies focused on long-term health-related quality of life (hrql) in va-ecmo survivors after cardiogenic shock. combes et al. questioned va-ecmo survivors about their hrql via the short-form questionnaire (sf- ). mean va-ecmo duration and follow-up were respectively days ( to ) and months ( to ). in comparison to sex-and agematched controls, va-ecmo survivors disclosed significantly lower role-physical score and a trend to a lower physical function, even though most patients recovered a good cardiac function with mean lvef % or underwent htx [ ] . these results were confirmed by other studies showing lower sf- values of physical functioning and role-physical scores in va-ecmo survivors compared to standard population [ , ] . these data however do not give any information with respect to the potential long-term burden of pulmonary alterations associated with va-ecmo, and future studies should be designed to address this issue, for example by performing delayed lung functional tests in long-term survivors of va-ecmo. va-ecmo elicits several pathophysiological disturbances which may significantly impact on lung integrity and function. first, the rapid development of a systemic inflammatory response with pulmonary involvement is an unavoidable consequence of the artificial va-ecmo circuitry. second, due to retrograde blood flow within the thoracic aorta, peripheral va-ecmo has the propensity to increase lv afterload, which may favor the congestion of alveoli already affected by the ongoing inflammation. third, persistent lung ischemia due to the partial shunting of the pulmonary circulation and reduced pulsatility of the bronchial circulation may elicit further cytotoxicity within the whole lung parenchyma. limited evidence from human observational studies and animal models indicates that va-ecmo support for more than a few days may lead to severe structural changes of the lung parenchyma and interstitial fibrosis, which could result in long-term functional limitation. clinicians in charge 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clinical significance techniques and outcomes of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension lung ischemia reperfusion injury: a bench-to-bedside review risk factor screening scale to optimize treatment for potential heart transplant candidates under extracorporeal membrane oxygenation outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock survival, quality of life and impact of right heart failure in patients with acute cardiogenic shock treated with ecmo health related quality of life after extracorporeal cardiopulmonary resuscitation in refractory cardiac arrest publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. authors' contributions ar and mk designed and conceived the paper. ar wrote the manuscript. ll provided figures and was a major contributor in writing manuscript. all authors contributed to the content of this paper and critically reviewed the final manuscript. ar edited individual contributions and finalized the manuscript. all authors read and approved the final manuscript. lucas liaudet is supported by a grant from the swiss national fund for scientific research (nr _ ).availability of data and materials not applicable.ethics approval and consent to participate not applicable. not applicable. the authors declare they have no competing interests. key: cord- -ny k k j authors: yeo, hye ju; kim, yun seong; kim, dohyung; cho, woo hyun title: risk factors for complete recovery of adults after weaning from veno-venous extracorporeal membrane oxygenation for severe acute respiratory failure: an analysis from adult patients in the extracorporeal life support organization registry date: - - journal: j intensive care doi: . /s - - - sha: doc_id: cord_uid: ny k k j background: as extracorporeal membrane oxygenation (ecmo) has been widely used, the patient quality of life following ecmo termination has become an important issue as same as the patient’s survival. to date, the factors affecting complete recovery of adult survivors from ecmo have not been investigated. methods: data from adult patients in the extracorporeal life support organization registry who received veno-venous ecmo between and were analyzed. multivariate logistic regression analyses were conducted. results: in total, patients with , days of veno-venous ecmo were reviewed. the overall survival to discharge rate after weaning from ecmo was . % (n = ), and . % (n = ) of the patients died during hospitalization. the discharge location varied as follows: . % (n = ) returned home, . % (n = ) were transferred to a referral hospital, . % (n = ) required hospital services, and . % (n = ) were discharged to other places. the patients were divided into two groups according to the discharge location: a complete recovery group (n = ) and a partial recovery group (n = ). in the multivariate analyses, age (≥ years) (odds ratio (or) . , % confidence interval (ci) . – . , p = . ), cardiac arrest before ecmo (or . , % ci . – . , p = . ), vasopressor use (or . , % ci . – . , p < . ), renal replacement therapy (or . , % ci . – . , p < . ), ecmo-related complications (or . , % ci . – . , p < . ), and long-term ecmo support (≥ weeks) (or . , % ci . – . , p < . ) were significantly associated with complete recovery. conclusion: complete recovery after veno-venous ecmo support is associated with the patient’s baseline condition, ecmo duration, and ecmo-related complications. respiratory ecmo should aim to increase both the survival and the quality of life after weaning from ecmo. survivors of acute respiratory distress syndrome (ards) often experience mental, physical, social, and functional impairments following hospital discharge [ ] [ ] [ ] . in previous studies, a substantial discrepancy between survival to discharge and long-term survival after ards was observed, and late mortality was increased by age and comorbidities, not the initial severity of the ards [ , ] . since then, many studies have focused on the quality of life of ards survivors [ ] [ ] [ ] [ ] . ecmo is recommended for the most severe form of ards as a lifesaving treatment. it is clear that this subset of patients will experience the sequelae of ards and critical illness, but data is lacking. in a previous multicenter cohort study of respiratory ecmo, . % of the patients died in hospital after weaning from ecmo, and a further . % died in the first months following hospital discharge [ ] . a substantial proportion of patients experienced significant unexpected re-exacerbation of ards after weaning from ecmo and were at risk of physical, functional, and psychological complications [ ] [ ] [ ] [ ] . accordingly, as same as the patient's survival, the patient's quality of life after ecmo termination has become an important issue as its use has increased. understanding the outcome after ecmo weaning and identifying the risk factors affecting complete recovery are crucial for the improvement of the long-term outcome of ecmo support. there have been several studies of the factors associated with mortality after weaning from ecmo, but the focus was not on complete recovery [ ] [ ] [ ] . in this study, we evaluated the unfavorable factors for complete recovery of adults after weaning from veno-venous (vv) ecmo for severe acute respiratory failure. the study design and data protection methods were presented to the extracorporeal life support organization (elso) steering committee, which allowed us to conduct a retrospective analysis of the elso registry data. this voluntary database collects baseline and outcome data on patients undergoing ecmo treatment in participating centers, with a total of centers contributing until . the data include age, sex, weight, primary and other diagnoses, discharge location, basic ventilation data, hemodynamic variables, arterial blood gas results, and clinical outcomes, including ecmo complications. all vv ecmo records between the years and were extracted from the elso database, excluding those for pediatric and neonatal patients, patients on venoarterial ecmo (n = , ). for the analysis of the postweaning outcomes, we excluded patients who were discharged with ecmo (n = ) and those who died while receiving ecmo (n = ). the other exclusion criteria included multiple ecmo runs, where ecmo was used as a bridge to transplantation, and unknown discharge location (n = ). missing data were not imputed. postweaning outcomes were presented as survival to discharge or death. survivors were classified into two groups, namely, complete recovery or partial recovery, depending on the discharge location. the complete recovery (cr) group comprised patients who were discharged to home, whereas the partial recovery (pr) group comprised patients who required hospital services, were transferred to a referral hospital, or were discharged to other places (fig. ) . the analysis was approved by the institutional review board (pusan national university yangsan hospital, - - ), and the need for informed consent was waived. continuous variables were examined for normality using the shapiro-wilk test. normally distributed variables were compared using the student's t test, whereas nonnormally distributed variables were compared using the kruskal-wallis test. categorical variables were examined using fisher's exact test or the chi-squared test. a value of p < . was defined as statistically significant. to evaluate the factors associated with cr after weaning from ecmo, logistic regression analysis was conducted. all potential clinical factors were evaluated using univariate analysis, and multivariate logistic regression analysis was conducted for variables with p value < . . the backward stepwise method was used for multivariate analysis, with entry and removal p values set at . . statistical analysis was performed using the r software (r foundation for statistical computing, vienna, austria, ). in total, patients with , days of vv ecmo were analyzed (fig. ). the overall survival to discharge rate after weaning from ecmo was . % (n = ), and . % (n = ) of the patients died during hospitalization. the discharge location varied as follows: . % (n = ) returned home, . % (n = ) were transferred to a referral hospital, . % (n = ) required hospital services, and . % (n = ) were discharged to other places. the patients were divided into two groups: the cr group (n = ) and the pr group (n = ). summary characteristics are presented and compared between the groups in table . significant differences in sex, age, and body weight were observed when the cr group was compared with the pr group (males . % vs . %, p = . ; mean age . vs . years, p < . ; mean body weight . vs . kg; p < . ). the distribution of primary diagnosis was different between two groups (p < . ). in the cr group, bacterial pneumonia and viral pneumonia were less common (bacterial . % vs . %, viral . % vs . %, p < . ). the ventilator settings and hemodynamics before ecmo initiation were significantly different between the two groups: the mean peak inspiratory pressure, pf ratio, and arterial blood pressure were higher in the cr group (p = . , p = . , and p < . , respectively). cardiac arrest before ecmo initiation, renal replacement therapy (rrt) use, and a vasopressor requirement were less common in the cr group (p = . , p < . , and p < . , respectively). the use of rescue therapies before ecmo initiation significantly differed between the cr and pr groups (inhaled no % vs . %, p = . ; neuromuscular block (nmb) agent . % vs . %, p = . ). the clinical outcomes of ecmo are outlined in table . the mean ecmo duration (days) was shorter (p < . ), and the proportion of long-term ecmo support (≥ weeks) was significantly lower in the cr group (p < . ). the rate of ecmo-related complications was significantly lower in the cr group ( . % vs . %, p < . ), including cardiovascular, mechanical, neurological, pulmonary, and renal complications ( table ) . the rates of cr and ecmo complications were inversely related to ecmo duration (fig. ) . as the ecmo duration increased, the cumulative incidence of ecmo complications increased, but the cumulative proportion of cr decreased. ci . - . , p < . ), ecmo-related complications (or . , % ci . - . , p < . ), and long-term ecmo support (≥ weeks) (or . , % ci . - . , p < . ) were significantly associated with cr (fig. ) . the odds ratio of each of the ecmo-related complications for cr is presented in additional file . this study revealed that only one third of patients returned home, and a substantial proportion of patients required additional hospitalization or hospital services despite surviving to discharge. the age, cardiac arrest before ecmo, severity of organ failure (vasopressor or rrt use), ecmo-related complications, and long-term ecmo support had unfavorable effects on cr. these results indicate that not only the patient's baseline condition but also the ecmo duration and ecmo-related complications are important for cr following ecmo support, and survival does not guarantee cr. in this study, the proportion of ecmo survivors who required transfer to another hospital or continued hospital services was higher than in other critical care populations [ ] [ ] [ ] . the prolonged use of medical services in many survivors implied that a substantial proportion of survivors did not achieve a cr when compared with survivors of other critical illnesses. the long-term prognosis of ards in the pre-ecmo era is mainly affected by non-modifiable factors, such as age and initial comorbidities [ ] [ ] [ ] . these are different from those in a specific population of respiratory ecmo patients. recovery status was associated with ecmo-related factors in values are expressed as mean ± standard deviation or n (%) copd chronic obstructive pulmonary disease, ards acute respiratory distress syndrome; ecmo extracorporeal membrane oxygenation, pip peak inspiratory pressure, peep positive end expiratory pressure, abp arterial blood pressure, rrt renal replacement therapy, no nitric oxide, nmb neuromuscular blockade values are expressed as mean ± standard deviation or n (%) cr complete recovery, pr partial recovery, ecmo extracorporeal membrane oxygenation addition to baseline characteristics, such as age and initial severity. in clinical practice, long-term maintenance of ecmo means that the patient's lung recovery is slow, which could be related to the underlying pathology requiring ecmo. however, the extended use of ecmo could inevitably be followed by several ecmo complications, as we and others have found (fig. ) [ , ] . ecmo complications have a significant adverse impact on the long-term prognosis of survivors, failure to wean from ecmo, and early mortality [ ] [ ] [ ] . this is a noteworthy point in that ecmo-related complications are potentially modifiable and could be improved. our findings could be the basis of further improvements in ecmo care by focusing on the reduction of cardiovascular, neurological, and renal complications (supplement ). this study has several limitations. first, this registry relies on voluntary reporting and may have a selection bias with such a heterogeneous group of patients. there are concerns that cases with poor clinical outcomes may be underreported, but this data reflect the clinical course after respiratory ecmo. secondly, the functional status of the patient after discharge was only estimated on the basis of the discharge locations, and the health-related quality of life or respiratory function of the survivors was not evaluated. due to limited information from the original registry, the possibility of overestimates of cr exists. third, this registry did not include information regarding specific treatments for the primary diagnosis. therefore, we cannot evaluate the impact of specific treatments for primary diagnosis on patient outcomes. fourth, this registry did not include information about weaning strategy of ecmo and other adjunctive strategies of mechanical ventilation. despite these limitations, the main strength of our study is the large scale of the cohort. the long-term maintenance of ecmo and in conclusion, on the basis of a large scale international cohort, a substantial number of patients with severe acute respiratory failure who successfully terminated ecmo did not achieve cr. the overall home discharge rate was only . %, and old age, baseline organ failure, delayed resolution of respiratory dysfunction, and ecmo complications hindered recovery after weaning from ecmo. future research should focus on the reduction of the modifiable risk factors to facilitate the cr of patients after ecmo. supplementary information accompanies this paper at https://doi.org/ . /s - - - . additional file . logistic regression odds ratio for complete recovery of each ecmo 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caregivers threeyear outcomes for medicare beneficiaries who survive intensive care what's next after ards: longterm outcomes determinants of long-term outcome in icu survivors: results from the frog-icu study determinants of mortality after hospital discharge in icu patients: literature review and dutch cohort study duration of ecmo is an independent predictor of intracranial hemorrhage occurring during ecmo support hemorrhagic complications during extracorporeal membrane oxygenation -the role of anticoagulation and platelets extracorporeal membrane oxygenation for life-threatening asthma refractory to mechanical ventilation: analysis of the extracorporeal life support organization registry impact of bloodstream infections on catheter colonization during extracorporeal membrane oxygenation low-dose heparin during extracorporeal membrane oxygenation treatment in adults publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we received data from the extracorporeal life support organization (elso) registry committee. we thank the elso and peter rycus for their support. we also appreciate all elso centers for their elaborate work and patient assistance. received: april accepted: august authors' contributions hy analyzed and interpreted the data. dk and yk were validated the results. hy and wc were major contributors in writing the manuscript. all authors read and approved the final manuscript. ethics approval and consent to participate the analysis was approved by the institutional review board (pusan national university yangsan hospital, - - ), and the need for informed consent was waived. the authors report no conflicts of interest.author details key: cord- - xmibi authors: gimeno-costa, ricardo; barrios, marcos; heredia, tomás; garcía, carmen; hevia, luis de title: covid- respiratory failure: ecmo support for children and young adult patients() date: - - journal: an pediatr (engl ed) doi: . /j.anpede. . . sha: doc_id: cord_uid: xmibi nan severe acute respiratory syndrome coronavirus (sars-cov- ) affects adults predominantly, with the greatest number of admissions to the intensive care unit (icu) and highest mortality found in this age group. although coronavirus disease (covid- ) in children has been described as being less severe with a shorter recovery time, we present the case of a female patient aged years, previously healthy and with no known contacts with covid- , that suffered severe pneumonia due to infection by sars-cov- requiring venovenous extracorporeal membrane oxygenation (ecmo) and experienced a full recovery. the patient presented to the emergency department of the regional hospital in her area with cough and fever of days' duration. the chest radiograph evinced pneumonia (figure a), which prompted admission to the inpatient ward. at hours, the pcr test for detection of sars-cov- turned out positive, so prescriptions were made for ritonavir/lopinavir (for up to days), hydroxychloroquine (for up to days), azithromycin (for up to days) and interferon - b (for up to days). on the same day, the condition of the patient worsened, as she developed tachycardia, tachypnoea, dyspnoea, fever ( . c) and her oxygen saturation (sao ) dropped to % ( l/min of supplemental oxygen). the patient was transferred to the icu and immediately required orotracheal intubation and invasive mechanical ventilation ( figure b ). in the hours that followed, the patient was managed with neuromuscular blocking agents, a positive end-expiratory pressure (peep) of to cmh o, inhaled nitric oxide and ventilation in the prone position ( sessions). after days in the picu, the partial pressure of oxygen (pao ) and the pao /fraction of inspired oxygen (fio ) worsened (the latter dropped to mmhg for h), which prompted activation of the mobile ecmo team of the tertiary care referral hospital in our autonomous community. the patient was connected to a portable ecmo system (cardiohelp ® , maquet cardiopulmonary ag, hirrlingen, germany) with a femoral-jugular veno-venous configuration (figure c): f multistage drainage cannula and f return cannula. after connection to the ecmo system, the patient was transferred to the icu of the referral hospital. on arrival, she had a heart rate of bpm and a blood pressure of / mmhg with administration of noradrenaline at a dose of . μg/kg/minute. she received ventilation with a tidal volume of ml/kg of body weight, a fio of % and a peep of cmh o. the initial ecmo blood flow was . l/min with a fio of % (with a sweep of l/min). the salient findings were lymphopaenia, marked elevation of interleukin , c-reactive protein, ferritin and d-dimer levels, and a negative troponin test (table ) . at admission in the icu of our referral hospital, we initiated treatment with tocilizumab (initial dose of mg followed by mg/ h after), methylprednisolone ( mg/kg/ h, doses) and switched antiviral treatment to remdesivir (initial dose of mg followed by mg/ h for days). the patient responded favourably. the levels of proinflammatory cytokines went down and pulmonary function improved: increase in the pao :fio ratio and improvement in dynamic compliance with a lower peep (table ) . after hours, it became possible to discontinue ecmo and extubate the patient. after days in the icu and in the inpatient ward of the referral hospital, the patient was discharged home without need of supplemental oxygen and was able to walk unassisted (negative pcr test for sars-cov- ) ( figure d ). extracorporeal membrane oxygenation should be considered salvage therapy in cases refractory to conventional mechanical ventilation, ventilation in the prone position and/or recruitment manoeuvres. the frequency of ecmo utilization during the covid- pandemic has been of . % to % of all hospitalised patients. in europe, as of may , , adult patients have required support with ecmo. although cases of pneumonia due to sars-cov- have been reported in infants , children and young adults, these patients have generally had good outcomes and rarely required extracorporeal life support. our patient developed severe pneumonia refractory to standard therapy and required ecmo. the european survey of neonatal/paediatric covid- patients in ecmo includes few patients, including ours. adult patients with covid- need between and days of ecmo to recover. in the case of our patient, days of ecmo sufficed to maintain oxygenation and allowed delivery of ultra-protective ventilation until the inflammatory response abated. we did not detect any adverse effects of the combination of antiviral and anti-inflammatory treatments used in the patient. we also did not need to adjust the usual dosage, so we surmise that there were no pharmacokinetic alterations associated with the use of the circuit or the extracorporeal membrane. many articles published during the current pandemic describe the course of disease in patients that remain in the icu (even under ecmo). ours is the first case of a paediatric patient managed with veno-venous ecmo that has fully recovered and been discharged home free of sequelae. in this case, extracorporeal life support proved safe (including an interhospital transfer), so it can be contemplated as an option in children and adolescents for management of covid- if their condition requires such support. figure plain chest radiograph. a) chest radiograph in emergency department of the regional hospital b) chest radiograph at admission in icu of regional hospital (prone position). c) chest department at admission to icu after transfer to referral hospital (day of ecmo). d) chest radiograph in inpatient ward of referral hospital (discharge day). clinical characteristics of coronavirus disease in china sars-cov- infection in children planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases european survey on ecmo in covid- pts at / / primer caso de infección neonatal por sars-cov- en españa coronavirus disease in critically ill children: a narrative review of the literature. pediatr crit care med key: cord- - tgo authors: yang, yang; rali, aniket s; inchaustegui, christian; alakbarli, javid; chatterjee, subhasis; herlihy, james p; george, joggy; shafii, alexis; nair, ajith; simpson, leo title: extracorporeal membrane oxygenation in coronavirus disease -associated acute respiratory distress syndrome: an initial us experience at a high-volume centre date: - - journal: card fail rev doi: . /cfr. . sha: doc_id: cord_uid: tgo nan ecmo is a well-established salvage therapy in the treatment of severe refractory ards. however, its role in the treatment of covid- associated ards currently remains unknown. our report describes the clinical course of covid- patients treated with ecmo at a major highvolume academic medical centre in the us. the key findings of our study are as follows. first, the majority of our patients were successfully weaned off ecmo and continue to show clinical improvement. second, covid- patients require a prolonged runtime on ecmo prior to being weaned off. third, the resp score appears to be a reliable measure in predicting outcomes among covid- patients treated with ecmo. intensive care unit (icu) patients. as previously mentioned, ecmo renders clinical benefit by allowing 'lung rest' ventilation, and thus minimising the risk of ventilator-induced lung injury in non-complaint lungs. therefore, it is imperative that ecmo be initiated early on in the disease process before irreversible lung damage ensues. the average number of days on mechanical ventilation prior to ecmo in the shanghai cohort was just over days, whereas that of our cohort was significantly lower at . days. the optimal selection of patients most likely to benefit from ecmo also appears to have contributed to the differences in outcomes between our cohort and the shanghai cohort. in our study, we used the resp score to calculate the probability of hospital survival and used % as our arbitrary cut-off for who was offered treatment with ecmo. on the contrary, ecmo was offered more broadly in the shanghai cohort to any patient that met any of the following criteria, despite optimal mechanical ventilation: pao /fio < mmhg for > hour; pao /fio < mmhg for > hours; and the existence of uncompensated respiratory acidosis with ph < . for > hour. it is crucial to appreciate that ecmo is a resource-intensive, highly-specialised and expensive form of life support, with the potential of significant complications, and thus should only be reserved for truly refractory cases that are most likely to benefit from it. while the resp score has not been directly validated in the apache = acute physiology and chronic health evaluation ecmo = extracorporeal membrane oxygenation sofa = sequential organ failure assessment extracorporeal membrane oxygenation (ecmo) in patients with h n influenza infection: a systematic review and meta-analysis including studies and patients receiving ecmo clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china extracorporeal membrane oxygenation for coronavirus disease extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in covid- : experience with patients clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected: interim guidance. geneva: who surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. the respiratory extracorporeal membrane oxygenation survival prediction (resp) score key: cord- -kcu guxa authors: laimoud, mohamed; alanazi, mosleh title: the clinical significance of blood lactate levels in evaluation of adult patients with veno-arterial extracorporeal membrane oxygenation date: - - journal: egypt heart j doi: . /s - - - sha: doc_id: cord_uid: kcu guxa background: veno-arterial ecmo is a life-supporting procedure that can be done to the patients with cardiogenic shock which is associated with hyperlactatemia. the objective of this study was to detect the validity of serial measurements of arterial lactate level in differentiating hospital mortality and neurological outcome after va-ecmo support for adult patients with cardiogenic shock. all consecutive patients ≥ years admitted with cardiogenic shock and supported with va-ecmo between and in our tertiary care hospital were retrospectively studied. results: the study included patients with a mean age of . ± . years, a mean bmi of . ± and mostly males ( . %). the in-hospital mortality occurred in . % and acute cerebral strokes occurred in . % of the enrolled patients. the non-survivors and the patients with acute cerebral strokes had significantly higher arterial lactate levels at pre-ecmo initiation, post-ecmo peak and after h of ecmo support compared to the survivors and those without strokes, respectively. the peak arterial lactate ≥ . mmol/l measured after ecmo support had . % sensitivity and . % specificity for predicting hospital mortality [auroc . , p < . ], while the arterial lactate level ≥ . mmol/l after h of ecmo support had . % sensitivity and . % specificity for predicting hospital mortality [auroc . , p < . ]. the peak lactate ≥ . mmol/l measured after ecmo support had . % sensitivity and % specificity for predicting cerebral strokes [auroc . , p < . ], while the lactate level ≥ . mmol/l after h of ecmo support had . % sensitivity and . % specificity for predicting cerebral strokes [auroc . , p < . ]. progressive hyperlactatemia (or = . , % ci . – . , p = . ) and increasing sofa score after h (or = . , % ci . – . , p < . ) were significantly associated with in-hospital mortality after va-ecmo support. post hoc analysis detected a significantly high frequency of hypoalbuminemia in the non-survivors and in the patients who developed acute cerebral strokes during va-ecmo support. conclusion: progressive hyperlactatemia after va-ecmo initiation for adult patients with cardiogenic shock is a sensitive and specific predictor of hospital mortality and acute cerebrovascular strokes. according to our results, we could recommend early va-ecmo initiation to achieve adequate circulatory support and better outcome. veno-arterial extracorporeal membrane oxygenation (va-ecmo) is a life-supporting procedure that can be given to the patients with cardiac dysfunctions requiring urgent cardiopulmonary support [ ] . cardiogenic shock is an emergency with a high mortality despite all efforts in diagnostic and therapeutic managements. the critical reduction of oxygen supply and organ perfusion during the shock state are associated with affection of the end organs like the brain, kidney and gastrointestinal tract resulting in multi-organ dysfunction syndrome [ ] [ ] [ ] . lactate is a metabolite produced during anaerobic glycolysis with impaired oxygen delivery and tissue perfusion. hyperlactatemia was described in cardiogenic shock due to sympathetic nervous activation, accelerated glycolysis and metabolism with the use of inotropic drugs [ , ] . hyperlactatemia has been proven to be associated with increased mortality among different critically ill patients including those after cardiac surgeries [ ] [ ] [ ] . the objective of this study was to detect the validity of serial measurements of arterial lactate level in differentiating in-hospital mortality and neurological outcome after va-ecmo support for patients with cardiogenic shock. all consecutive patients ≥ years old with cardiogenic shock who received va-ecmo support at our tertiary care hospital between and were retrospectively enrolled in this study. we excluded the patients who had cardiac arrest and cardiopulmonary resuscitation (cpr). our study was approved by the hospital ethics committee without a need to get informed consents because of being retrospective. the integrated compliance information system (icis) provided the database to get the clinical and laboratory variables of the enrolled patients. the studied patients got extracorporeal cardiopulmonary support via maquet cardiohelp and rotaflow ecmo machines (getinge group, germany). our hospital has ecmo machines restricted to the cardiac critical care units. there are cardiohelp devices with the serial numbers , and and rotaflow devices with the serial numbers , , , and . we have used maquet heart-lung support (hls) module advanced and cannulae which are biocompatible with bioline coating. the module consist of a low-damage centrifugal pump with an oxygenator and integrated sensors that allow bubble detection and continuous measurements of haemoglobin, haematocrite, venous oxygen saturation, module internal pressure, venous and arterial pressures and temperatures. veno-arterial ecmo support was indicated during cardiac surgery due to either failed weaning from cardiopulmonary bypass or rapid haemodynamic deterioration after weaning. pre-operative va-ecmo or ecmo without cardiotomy were initiated for refractory cardiogenic shock despite optimal resuscitation efforts. after ecmo initiation, the blood flow was adjusted according to clinical assessments including urine output, clearance of hyperlactatemia and mixed venous oxygen saturation. blood lactate levels were measured by arterial blood gas analysis which had been done hourly in the first few hours after ecmo initiation till haemodynamics stabilization then every h till clearance. titration of oxygen flow and sweep flow were gradually done to achieve acceptable blood gases. the temperature of heat exchanger was adjusted to maintain the normal body temperature and avoiding hypothermia especially post-cardiotomy. minimizing the doses of inotropic drugs was done to help myocardial recovery but keeping ventricular ejection to avoid ventricular thrombosis. midazolam and morphine intravenous infusions were routinely used to achieve adequate sedation and analgesia. all studied patients were mechanically ventilated on the pressure regulated volume-controlled (prvc) mode at breaths/ min with a low tidal volume of - ml/kg, a positive endexpiration pressure (peep) of - mmhg and the inspired oxygen fraction was - %. anticoagulation was done via intravenous unfractionated heparin infusion which was adjusted according to heparin assay (target . - . units/ml), antithrombin iii (goal - %) and clinical tolerance. platelets were transfused to keep count more than ( /l), packed red blood corpuscles were transfused to maintain the haematocrite at - % and cryoprecipitate transfusions were given to keep fibrinogen level more than (gm/l). all studied patients underwent daily neurological evaluation after withdrawal of sedation including glasgow coma scale assessment, pupil sizes and reactivity to light and brain stem reflexes. continuous brain oxygenation monitoring (rso %) was routinely done to our va-ecmo-supported patients using the near-infrared spectroscopy (nirs) technique via frontal probes. if any neurological manifestations after sedation withdrawal or significant rso % change happened, brain computed tomography (ct) imaging was done as early as possible. the clinical and laboratory data of studied patients were collected. the blood lactate levels were collected at points: pre-ecmo initiation, peak level and h after ecmo support. the sequential organ failure assessment (sofa) score was calculated on icu admission and ecmo initiation then after h to get the Δ sofa. the worst values for each variable were used during sofa calculation. all studied patients were divided according to mortality into the survivors and non-survivors and according to neurological manifestations into groups: cerebral damage and non-cerebral damage groups. data were analysed using the statistical package of social science software program, version (spss). the continuous variables were described as mean ± standard deviation (sd) or median with interquartile range (iqr), while the nominal variables were reported as total number and percentages. p value of less than . was considered statistically significant. kolmogorov-smirnov test was used as a normality test to evaluate the variables and choose the type of statistical tests. receiver operating characteristic (roc) curves were done to evaluate the ability of blood lactate level to predict hospital mortality and neurological damage. in this analysis, area under roc curve (auroc) was calculated to quantify the accuracy of the predictive model. we studied consecutive adult patients with cardiogenic shock that failed medical management and required va-ecmo support. the mean age of studied the non-survivors group had significantly frequent chronic kidney disease (ckd), cardiac surgeries, aki, renal replacement therapy and longer icu stay compared to the survivors group. the non-survivors had higher mean initial sofa score with an increased trend after h compared to the survivors. the patients with acute cerebral strokes had significantly frequent ckd, cardiac surgeries, longer cpb and aortic cross clamping times, lesser bmi and longer icu stay compared to the patients without cerebral damage. the patients who developed acute cerebral strokes had higher mean initial sofa score with an increased trend after h compared to those who did not develop brain damage. atrial fibrillation was a significant finding in the non-survivors and the patients with cerebral damage. the non-survivors had significantly frequent intracerebral bleeding and the patients with cerebral damage had significantly high hospital mortality. central va-ecmo cannulation was significantly frequent in the non-survivors and those with cerebral damage (table ) . the pre-ecmo mean blood lactate level was . ± . vs . ± (p < . ) and the median base excess was − . [− . to − . ] vs − . [− to − . ] (p < . ) in the survivors and non-survivors, respectively. the pre-ecmo mean blood lactate level was . ± . vs . ± . (p = . ) and the median base excess was − . [− . to − . ] vs − [− . to − . ] (p = . ) in the patients with and without cerebral damage, respectively. after ecmo support, the mean peak arterial blood lactate level was ± vs . ± . (p < . ) and mean blood lactate after h was . ± . vs . ± . (p < . ) in the survivors and non-survivors groups, respectively. the mean peak lactate level was ± . vs . ± (p < . ) and mean lactate level after h was . ± vs . ± . (p < . ) in the patients with and without cerebrovascular strokes, respectively ( table , fig. ) . as compared to the survivors, the non-survivors had significant hypoalbuminemia (p = . ) and higher serum creatinine level (p = . ). as compared to the patients without cerebral damage, the patients with cerebrovascular strokes had significant hypoalbuminemia (p = . ) and hypofibrinogenemia (p = . ) ( table ) . fig. ). a multivariable regression analysis was done to get the odds ratio with the hospital mortality as the dependent variable. progressive hyperlactatemia (or = . , % ci . - . , p = . ) and increasing sofa score after h (or = . , % ci . - . , p < . ) were significantly associated with in-hospital mortality after va-ecmo support. despite haemodialysis central ecmo cannulation, af and cardiac surgeries were significant in the non-survivors group in the univariate analysis, there were not significantly associated with mortality in the multivariable regression analysis (table ). veno-arterial ecmo is used in cases of refractory cardiogenic shock including post-cardiotomy shock to rapidly achieve circulatory support and protect organs perfusion allowing time for cardiac recovery and avoiding multiorgan system failure. our study revealed in-hospital mortality of . % which is consistent with other large ecmo registries [ ] [ ] [ ] . progressive hyperlactatemia and delayed clearance during the first h after ecmo support were associated with the increased mortality in our both univariate and multivariate analysis (or = . , % ci . - . , p = . ). the non-survivors had significantly higher pre-ecmo lactate level and metabolic acidosis as compared to the survivors. schmidt et al. [ ] described the association of pre-ecmo significant metabolic acidosis and mortality but did not describe the lactate level in those patients. chen et al. [ ] described the pre-ecmo greater metabolic acidosis and hyperlactatemia in the non-survivors supported with va-ecmo and used pre-ecmo lactate level to develop the modified save score. our results showed that the peak blood lactate had a better performance (auroc . , % ci . - . ; p < . ) and lactate level after h of ecmo initiation had the best performance regarding sensitivity and specificity in differentiating mortality (auroc . , % ci . - . ; p < . ) . this finding can be explained by impaired tissue perfusion despite achieving haemodynamic stabilization and the use of inotropic drugs. the use of β adrenergic stimulants accelerates glycolysis and gluconeogenesis with increases in blood lactate levels [ , ] . li et al. [ ] described the negative correlation between blood levels of lactate after ecmo initiation and the mean arterial blood pressure (map) and suggested that achieving higher map might reduce lactate levels. rastan et al. [ ] studied va-ecmo support for postcardiotomy shock and described blood lactate level more than mmol/l immediately after ecmo initiation as a significant predictor of mortality (mortality . %; or . ; p < . ) while persistently high lactate levels more than mmol/l after and h of ecmo initiation were associated with the highest mortalities of . % and . %, respectively. in our analysis, we found the presence of pre-ecmo chronic renal impairment or development of post-ecmo acute kidney injury and haemodialysis were highly significant in the non-survivors. schmidt et al. [ ] described the presence of renal failure as a significant variable in the mortality group after va-ecmo support. however aso et al. [ ] found that renal impairment was not a significant variable but the use of haemodialysis was significantly associated with mortality in va-ecmo-treated patients. rastan et al. [ ] described the development of acute renal failure or acute hepatic failure as predictors of mortality. we used the sofa scoring to assess the magnitude of organ failure and to detect the trend after ecmo support. the non-survivors had higher mean initial sofa score with an increasing trend compared to the survivors. together with rising blood lactate level, the increasing sofa score after h of va-ecmo support were the predictors of hospital mortality in our multivariate regression analysis. ferreira et al. [ ] described our results showed that acute cerebrovascular strokes occurred in . % of patients which is comparable to other studies of acute cerebral strokes during va-ecmo support especially post-cardiotomies [ , ] . the blood lactate level after ecmo support was linked to the neurological injury and other outcomes in different studies but with different cut-off values [ , , ] . our post hoc analysis detected a significantly high frequency of hypoalbuminemia in the non-survivors and in the patients who developed acute cerebral strokes during va-ecmo support. the hypoalbuminemia was linked to a higher mortality in all hospitalized patients in some studies [ , ] . other studies described the occurrence of hypoalbuminemia in some patients admitted with acute large cerebrovascular strokes in haemodynamically stable patients and the low albumin level was linked to mortality of those patients [ , ] . recently, huang et al. described hypoalbuminemia as being strongly associated with mortality of va-ecmo-treated patients [ ] . finally, our study revealed that the hospital mortality and neurological outcome of va-ecmo were significantly associated with the severity of pre-ecmo shock state and the appropriate recovery of organs perfusion after ecmo support as indicated with changes of blood lactate levels. repeated blood lactate measurements after va-ecmo initiation help to detect the magnitude and duration of impaired tissue oxygenation and organs perfusion and predict outcome. progressive hyperlactatemia after va-ecmo initiation for adult patients with cardiogenic shock is a sensitive and specific predictor of hospital mortality and cerebrovascular strokes. according to our results, we recommend early va-ecmo initiation to achieve adequate circulatory support and better outcome. our work was a single-centre retrospective study. extracorporeal life support in critically ill adults ecmo in cardiac arrest and cardiogenic shock cardiogenic shock: pathophysiology, clinics, therapeutical options and perspectives cardiogenic shock preface biomarkers in critical illness effects of cardiogenic shock on lactate and glucose metabolism after heart surgery serum lactate as a predictor of mortality in emergency department patients with infection occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients lactate clearance time and concentration linked to morbidity and death in cardiac surgical patients predicting survival after ecmo for refractory cardiogenic shock: the survival after veno-arterial-ecmo (save)-score resource use trends in extracorporeal membrane oxygenation in adults: an analysis of the nationwide inpatient sample - ecmo use and mortality in adult patients with cardiogenic shock: a retrospective observational study in u the modified save score: predicting survival using urgent veno-arterial extracorporeal membrane oxygenation within hours of arrival at the emergency department comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. a prospective, randomized pilot study relation between muscle na+k+ atpase activity and raised lactate concentrations in septic shock: a prospective study the early dynamic behavior of lactate is linked to mortality in postcardiotomy patients with extracorporeal membrane oxygenation support: a retrospective observational study early and late outcomes of consecutive adult patients treated with extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock in-hospital mortality and successful weaning from venoarterial extracorporeal membrane oxygenation: analysis of , patients using a national inpatient database in japan serial evaluation of the sofa score to predict outcome in critically ill patients acute neurological complications in adult patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation support hypoalbuminemia is a strong predictor of -day all-cause mortality in acutely admitted medical patients: a prospective, observational, cohort study low albumin levels are associated with mortality risk in hospitalized patients hypoalbuminemia in acute ischemic stroke patients: frequency and correlates relationship between admission hypoalbuminemia and inhospital mortality in acute stroke prognostic factors for survival after extracorporeal membrane oxygenation for cardiogenic shock publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we would like to thank the cardiac surgical intensive care unit (adult csicu) team of our hospital for their excellent work. all authors contributed to the research and approved the final manuscript. ml has taken part in the design of the study; collection, analysis and interpretation of the data; and drafting of the manuscript. ma has taken part in the design of the study and analysis, collection and interpretation of the data. the authors did not receive any funding for this study. the data used in this study are available from the corresponding author upon a reasonable request. the study was approved by the ethical committee of king faisal specialist hospital and research center and exempted from a specific consent, being a retrospective analytic study that reveals no identifiable private information.the study was given a reference number . the authors had no competing interests to declare.received: june accepted: october key: cord- - ghjewxc authors: douedi, steven; alshami, abbas; costanzo, eric title: extracorporeal membrane oxygenation as treatment of severe covid- infection: a case report date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ghjewxc novel coronavirus (covid- ) is a severe respiratory infection leading to acute respiratory distress syndrome (ards) accounting for thousands of cases and deaths across the world. several alternatives in treatment options have been assessed and used in this patient population. however, when mechanical ventilation and prone positioning are unsuccessful, venovenous extracorporeal membrane oxygenation (vv-ecmo) may be used. we present a case of a -year-old female, with no significant medical history and no recent history of exposure to sick contacts, presented to the emergency department (ed) with fever, severe shortness of breath, and flu-like symptoms with a positive covid- test. ultimately, she worsened on mechanical ventilation and prone positioning and required vv-ecmo. the use of vv-ecmo in covid- infected patients is still controversial. while some studies have shown a high mortality rate despite aggressive treatment, such as in our case, the lack of large sample size studies and treatment alternatives places healthcare providers against a wall without options in patients with severe refractory ards due to covid- . the novel coronavirus (covid- ) is a respiratory tract infection that has resulted in a pandemic, infecting more than , , humans and claiming the lives of over , in less than six months [ ] . the disease classically results in hypoxemic respiratory failure requiring oxygen supplementation using low and high delivery systems, as well as mechanical ventilation. however, when all these measures fail, options become very limited. one of these potential alternatives is the extracorporeal membrane oxygenation (ecmo). evidence on ecmo in covid- patients remains controversial, as the immunological side effects of ecmo can further compromise the already debilitated immune system fighting covid- [ ] . we report a case of a covid- -positive patient who was managed with ecmo after no response to mechanical ventilation and prone positioning. a -year-old female with no significant medical history and no recent history of travel or exposure to sick contacts presented to the emergency department (ed) with a worsening dry cough, shortness of breath, and chest tightness, followed by fever, chills, and myalgias for four days duration. other reported symptoms included a mild sore throat and watery diarrhea. vital signs on admission were a temperature of . °fahrenheit (measured orally), a heart rate of beats per minute, a blood pressure of / mm hg, respiratory rate of breaths per minute, and oxygen saturation of % on room air ( % on liters nasal cannula). physical examination was pertinent for ill appearance and rhonchi over the left lung base. blood tests showed a white blood cell count of . cells/mm , lymphopenia of cells/mm , hemoglobin of . g/dl, potassium of . meq/l, aspartate aminotransferase (ast) of iu/l, alanine aminotransferase (alt) of iu/l, lactate of . mmol/l, and procalcitonin . ng/ml. polymerase chain reaction (pcr) tests for influenza a and b, metapneumovirus, adenovirus, parainfluenza, respiratory syncytial virus, and coronaviruses hku , nl , e, and oc were all negative. given the current pandemic, covid- was suspected, and a nasal swab was sent to be tested. a computed tomography scan of the chest was obtained and showed bilateral infiltrates ( figure ). bilateral diffuse scattered patchy ground-glass opacities throughout the lungs with more geographic mixed ground-glass and consolidative opacities in the lingular and superior segment of the left lower lobe extending to the posterior left lower lobe. mild to moderate patchy scattered ground-glass opacities were seen in the right lower lobe, as well as a perihilar right upper lobe with areas of peripheral ground-glass opacities the patient was started empirically on intravenous (iv) vancomycin, piperacillin-tazobactam, azithromycin, and hydroxychloroquine. over a one-day period, the patient's respiratory status progressively deteriorated, and she was subsequently intubated. on the following day, the covid- test came back positive, and the patient was continued on mg daily of hydroxychloroquine and mg twice daily of azithromycin. she was also started on high-dose vitamin c at a rate of grams iv twice daily, and mg of zinc sulfate via orogastric tube once daily. despite aggressive management, she developed severe acute respiratory distress syndrome (ards) and was requiring higher mechanical ventilation settings ( % fraction of inspired oxygen and of positive end-expiratory pressure). the decision was also made to begin prone positioning of the patient for hours a day for a ratio of arterial oxygen partial pressure to fractional inspired oxygen (p/f ratio) of < . liver enzymes continued to trend up (ast and alt ), and the patient developed acute kidney injury due to decreased organ perfusion. she was started on levophed for hemodynamic stability and to maintain a mean arterial pressure > . she was also given one dose ( mg/kilogram body weight) of tocilizumab, an anti-interleukin- receptor monoclonal antibody, in order to help control her cytokine storm. despite this, she continued to decompensate, and the patient was started on continuous venovenous hemodialysis (cvvhd) for renal failure and on venovenous extracorporeal membrane oxygenation (vv-ecmo). prior to vv-ecmo, an echocardiogram was performed which showed an ejection fraction of % - %, moderate pulmonary hypertension, and grade (mild) diastolic dysfunction. two days after starting vv-ecmo, the patient lymphocyte count was cells/mm , white blood cell count was . cells/mm , fibrinogen level < , and d-dimer , . she was started on lovenox, mg/kg, due to a severely elevated d-dimer; however, her platelet count decreased by greater than %, and she was switched to argatroban. heparininduced thrombocytopenia (hit) panel was sent and returned negative, but she remained on argatroban for anticoagulation due to the significant drop in her platelet count on heparin products. she began to develop ischemia in her fingers and toes bilaterally but was continued on levophed for hemodynamic stability and vv-ecmo. four days after the initiation of vv-ecmo, the patient developed an asystole rhythm and ultimately passed away. extracorporeal membrane oxygenation (ecmo) has remarkably progressed over recent years and became a reliable tool in severe cardiac and pulmonary dysfunction [ ] [ ] . venovenous ecmo (vv-ecmo) can be considered in patients with a pf ratio of - mm hg, murray score > , and a ph of < . on arterial blood glass [ ] . vv-ecmo allows deoxygenated blood to be pulled from the right atrium through a cannula allowing it to pass through an oxygenator and heat exchanger before being pumped back into the right atrium through another cannula [ , ] . there are no relative contraindications to vv-ecmo as the decision is made on a case-by-case basis; however, the patient's age and comorbidities must be taken into consideration and an echocardiogram should be performed prior to initiation to evaluate for right or left ventricular failure to confirm the nature of pulmonary failure [ , ] . complications of vv-ecmo include bleeding, infection, air embolism, heparin-induced thrombocytopenia (hit), and catheter/machine-associated dysfunction [ ] . despite these complications, some studies have shown that vv-ecmo significantly improves survival in severe acute respiratory failure, including patients with influenza a (h n )-related acute respiratory distress disease [ ] [ ] [ ] . vaquer et al. reported that % of patients who received vv-ecmo were successfully discharged from the hospital despite severe refractory ards [ ] . the use of ecmo in covid- patients is still controversial and has mixed results. li et al. reported seven covid- infected patients with p/f ratios < on vv-ecmo and was able to successfully wean three patients thus far; however, they had a mortality rate of % [ ] . yang et al. had similar results where five of six patients receiving ecmo for covid- infection died [ ] . it was found that a decreased lymphocyte count was associated with poor outcomes and death from covid- infections [ , ] . in our case presented, our patient did not respond to mechanical ventilation. due to a lack of alternatives, her young age, and no comorbidities, vv-ecmo was considered in our patient with severe ards (p/f ratio < ) due to the covid- infection. ultimately, her lymphocyte count was cells/mm and she did not respond to vv-ecmo and passed away. while most studies lack a significant sample size, this case adds to the concern on the use of ecmo in covid- patients. in patients with severe ards unresponsive to mechanical ventilation, prone positioning, and other alternatives, the need for further studies and understanding the role of ecmo in respiratory failure need to be assessed. vv-ecmo use in patients with severe refractory ards due to covid- infections is still controversial. while some studies have shown a high mortality rate despite aggressive treatment, such as in our case, they lack sufficient sample sizes. due to limited alternatives and treatment options for patients with severe refractory ards, studies evaluating the use of ecmo in covid- are desperately needed. human subjects: consent was obtained by all participants in this study. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. covid- ) outbreak covid- , ecmo, and lymphopenia: a word of caution veno-venous extracorporeal membrane oxygenation: cannulation techniques extra corporeal membrane oxygenation (ecmo) review of a lifesaving technology venovenous extracorporeal membrane oxygenation in intractable pulmonary insufficiency: practical issues and future directions extracorporeal membrane oxygenation rescue for h n acute respiratory distress syndrome: equipoise regained systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome. ann intensive care extracorporeal membrane oxygenation for coronavirus disease clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china key: cord- -zjfhpum authors: patangi, sanjay orathi; shetty, riyan sukumar; shanmugasundaram, balasubramanian; kasturi, srikanth; raheja, shivangi title: veno-arterial extracorporeal membrane oxygenation: special reference for use in ‘post-cardiotomy cardiogenic shock’ — a review with an indian perspective date: - - journal: indian j thorac cardiovasc surg doi: . /s - - - sha: doc_id: cord_uid: zjfhpum the ultimate goals of cardiovascular physiology are to ensure adequate end-organ perfusion to satisfy the local metabolic demand, to maintain homeostasis and achieve ‘milieu intérieur’. cardiogenic shock is a state of pump failure which results in tissue hypoperfusion and its associated complications. there are a wide variety of causes which lead to this deranged physiology, and one such important and common scenario is the post-cardiotomy state which is encountered in cardiac surgical units. veno-arterial extracorporeal membrane oxygenation (va-ecmo) is an important modality of managing post-cardiotomy cardiogenic shock with variable outcomes which would otherwise be universally fatal. va-ecmo is considered as a double-edged sword with the advantages of luxurious perfusion while providing an avenue for the failing heart to recover, but with the problems of anticoagulation, inflammatory and adverse systemic effects. optimal outcomes after va-ecmo are heavily reliant on a multitude of factors and require a multi-disciplinary team to handle them. this article aims to provide an insight into the pathophysiology of va-ecmo, cannulation techniques, commonly encountered problems, monitoring, weaning strategies and ethical considerations along with a literature review of current evidence-based practices. inability to wean off cardio-pulmonary bypass (cpb) is a morbid condition associated with cardiogenic shock secondary to impaired myocardial contractility. once the vicious cycle sets in, vital organ perfusion is compromised, culminating in severe metabolic derangement. the incidence of refractory cardiogenic shock post cardiotomy ranges from . to % [ , ] with a mortality rate as high as % [ ] . veno-arterial extracorporeal membrane oxygenation (va-ecmo) has gained popularity over the years as a 'bailout' option after conventional circulatory support methods have proved refractory in the operating room (or)/intensive care unit (icu). va-ecmo facilitates luxurious end-organ perfusion and adequate gas exchange and supports organ functionality allowing time for recovery/ bridge to decision. however, its usage has not been directly linked with early positive outcomes with few articles reporting increased mortality [ ] [ ] [ ] . post-cardiotomy va-ecmo is used in both adult and paediatric populations [ ] . the worldwide incidence of instituting post-cardiotomy va-ecmo varies between . and . % [ ] . the extracorporeal life support organization (elso) database states a substantial increase in its use over the last decade. the patient population in which this therapy has been used for dealing with post-cardiotomy cardiogenic shock (pccs) included those with renal insufficiency, prior myocardial infarction, critical left main coronary artery disease, redo-surgery and severe left ventricular (lv) dysfunction [ ] . age is not a contraindication for this therapy. va-ecmo has been used to tide over patients with pccs covering the ambit of cardiac surgery and transplantation. cannulation is the first decisive step for a smooth ecmo run that can be either central (atria-aortic) or peripheral (femoral veinfemoral artery/axillary artery) (fig. ) . a meta-analysis favours the peripheral route due to lesser transfusions, bleeding/ tamponade events and lower mortality [ ] . however, these observational studies were based on a small sample size without accounting for confounding factors like the patient pre-initiation condition, effect of lv unloading and the timing of ecmo initiation. notably, the use of temporary mechanical support following pccs is associated with higher vascular complications when the duration exceeds days [ ] and incidence of amputation even with distal limb perfusion is . % [ ] . offloading the lv reduces the myocardial oxygen demand and allows for quicker myocardial recovery with higher survival rates. the decision on cannulation should be expeditious with minimal blood loss ensuring the myocardium is fully rested to hasten recovery and is fundamental in ensuring survival following pccs. techniques of venting include insertion of an intra-aortic balloon pump (iabp), atrial septostomy, percutaneous ventricular assist device (vad) or direct cannulation of the lv apex [ ] . monitoring and maintenance on va-ecmo standard monitoring includes mean arterial pressure (map), central filling pressures, temperature, pulse oximetry and urine output. cardiac output (co) measurement by thermodilution technique is overestimated whereas pulse contour analysis is unreliable due to non-pulsatility [ ] . abnormal rhythm leads to ineffective lv ejections resulting in lv distension and myocardial injury. presence of an lv vent prevents distension while reversal to sinus rhythm can be achieved by cardioversion, antiarrhythmics, pacing or ablation [ ] . lv pulsatility is assessed by arterial pressure waveform. map is maintained in a range of - mmhg to ensure vital organ perfusion [ ] . temperature monitoring is crucial as ecmo has cooling effects and temperature elevations beyond the 'defined temperature regulated range' signal infection. vascular access, urinary catheter, pneumonia and surgical wound sites are potential sources of infection [ ] . hypothermia worsens coagulopathy and platelet dysfunction [ ] . transcranial doppler, near-infrared spectroscopy (nirs) and cerebral oximetry monitoring can detect cerebral hypoperfusion and upper body hypoxaemia. nirs helps to identify lower-extremity ischaemia in peripheral arterial cannulation [ ] . in va-ecmo, total systemic flow equals the sum of pump flow plus native co. cannulae selected should provide - ml/kg/min of flow, and when flows are maintained at %, it avoids stasis in the pulmonary vasculature [ ] . sweep gas flow titration regulates carbon dioxide (co ) levels while oxygenation depends on the fraction of delivered oxygen (o ), oxygenator blood flow and exposed surface area [ ] . va-ecmo is not an indication for mechanical ventilation, and patients may be extubated on va-ecmo support [ ] . for patients who require mechanical ventilation, there is limited data on optimal ventilation strategies. extrapolating veno-venous ecmo (vv-ecmo) literature, lung protective ventilation is commonly recommended, with - ml/kg tidal volume, cm h o positive end expiratory pressure (peep) and plateau pressure < cmh o to maintain < cmh o driving pressure (inspiratory pleural pressure-peep) [ ] . unfractionated heparin (ufh) remains the mainstay of anticoagulation due to quick onset of action and rapid reversibility. heparin monitoring relies on activated partial thromboplastin time (aptt) and anti-xa activity while activated clotting time (act) is unreliable in low to moderate doses of heparin ( . to iu/kg/h) [ ] . echocardiography enables assessment of biventricular function, aortic valve opening, cannula position, pericardial and pleural effusions and ventricular thrombus formation [ ] . mixed venous saturations (scvo ) and lactate levels are monitored for adequacy of tissue perfusion and o delivery to end organs. elevated lactate levels reflect tissue hypoxia and are associated with mortality [ ] . plasma free haemoglobin (pfhb) monitoring indicates haemolysis occurring in the ecmo circuit. pfhb levels > mg/dl increase risk of thrombosis due to affinity of the von willebrand factor to platelet glycoprotein gpib [ ] . no guidelines exist to decide the optimal time of weaning. recovery of adequate cardiac and respiratory function is a pre-requisite. some authors suggest weaning as early as - h [ ] but rarely beyond days, except in cases of postheart transplantation for resolution of pulmonary hypertension [ ] . recovery of cardiac function in the post-cardiotomy setting is limited and rare beyond days [ , ] . a longer duration of support is associated with increased complications and mortality [ ] . weaning is by a multidisciplinary consensus. cardiac index, pulmonary capillary wedge pressure, central venous pressure, pulse pressure > mmhg and map > mmhg with minimal haemodynamic support are indicators of cardiac function recovery [ ] . resolution of pulmonary oedema, lung recruitment manoeuvres and clearing of airway secretions by bronchoscopy to ensure partial pressure of o (pao )/fraction of inspired o (fio ) ratio > , fio < % on the ventilator and fio < % on ecmo circuit are desirable [ , ] . although end-organ recovery to pre-ecmo levels is important [ ] , complete recovery from acute tubular necrosis can take weeks; hence, complete resolution of renal function is not mandatory before weaning. the patient can be supported with haemodiafiltration during this period [ ] . a weaning trial assesses suitability to separate from the ecmo machine. assessment of right ventricular (rv) function is crucial [ ] . ecmo flows are reduced gradually with inotropic and respiratory support whilst being monitored by clinical and echocardiographic variables. cavarocchi et al. [ ] described a -stage weaning trial using a miniaturized transoesophageal echocardiogram (tee) with % positive predictive value. lv ejection fraction (lvef) > - %, aortic velocity time integral (vti) > cm, mitral lateral annulus systolic velocity > cm/s, rv ejection fraction > . %, no lv or rv distension and ability to maintain map with minimal inotropic supports indicate the possibility of a successful wean. assessments of tricuspid regurgitation, tricuspid annular plane systolic excursion or lv filling parameters are not reliable [ ] . among clinical variables analysed, pulsatility and lactate clearance predicted a successful wean. however, no threshold was identified [ , ] . biomarkers such as nterminal fragment of the b-type natriuretic peptide (bnp), troponin i, the mid regional fragment of the proatrial natriuretic peptide, proadrenomedullin and copeptin have poor predictive ability in va-ecmo weaning [ ] . fast and slow weaning strategies have been proposed [ , ] . westrope et al. described a unique technique of pump-controlled retrograde trial off. here, the pump speed is gradually decreased to encourage reversal of flow into the ecmo circuit which creates a controlled arterio-venous (a-v) shunt without a steep drop in systemic vascular resistance [ ] . the pulmonary artery catheter is a useful monitoring tool in the weaning/post-weaning phase [ ] . levosimendan improves weaning success. it works via non-adrenergic pathways with active metabolites producing effects that last - days [ ] . inhaled nitric oxide improves rv function by reducing pulmonary vascular resistance [ ] . total vessel density and perfused vessel density monitoring of sublingual microcirculation have been found to have a good association with aortic vti, lvef parameters during ecmo wean [ ] . pccs is an uncommon occurrence with high morbidity and mortality in cardiac surgery. this low co state is refractory to high inotropic and iabp use. in this scenario, va-ecmo is a bridge to decision/recovery. va-ecmo drains blood from the venous system and inputs into the arterial system causing a reduction in rv and lv preload and improving endocardial blood flow by decreasing lv end diastolic pressure. lv afterload is increased in higher map states which distends the lv and leads to pulmonary congestion [ ] . the higher flows via ecmo improve macroand micro-circulation [ ] . non-pulsatile flow produces atrophic changes in the medial layer of the aorta and reduces vascular contractility [ ] . the ecmo oxygenator is made of microporous polypropylene membrane containing hollow fibre bundles. the input gas flows within these bundles while blood passes over it. gas exchange is by diffusion. the o uptake is determined by fio , gradient across membrane fibres, surface area of oxygenator and ecmo flow while sweep gas controls co elimination. as co transfer is six times faster compared to o , failure to clear co indicates oxygenator failure [ ] . ischaemic damage due to shunting of pulmonary blood flow, inflammatory activation, collapsed lungs, ischaemiareperfusion damage and passive congestion from lv distension contribute to ecmo-induced lung damage [ ] . extubation is recommended to reduce lung damage. however, patients have reduced alveolar ventilation secondary to co clearance by ecmo. to prevent post-extubation atelectasis, it is important to maintain co and ph levels by non-invasive ventilation along with sweep gas flow titration [ ] . although va-ecmo provides gas exchange in addition to circulatory support, native lung function is important in peripheral ecmo as myocardial and cerebral oxygen delivery is determined by o content of blood exiting the lv [ ] . studies comparing pulsatile with non-pulsatile flows have found maintained cerebral metabolism and autoregulation with both patterns provided map is > mmhg [ ] . varying levels of organ damage prior to ecmo improve after establishing adequate flows. effective venous drainage relieves congestion, further improving organ circulation. pulsatile flow enhances end organ recovery and splanchnic circulation compared to non-pulsatile flows although microcirculation is maintained in both patterns [ ] . rate of renal recovery is comparable in either flow patterns [ ] . there is no difference in clinical outcomes in either pattern provided adequate flows are maintained [ ] . lymph flow is dependent on muscle activity and pulsatility. arterial pulsation is a primary determinant of lymphatic drainage in supine patients. non-pulsatile flows lead to peripheral oedema and intestinal congestion [ ] . the blood-material interface activates coagulation, fibrinolytic and inflammatory systems releasing proinflammatory mediators that lead to endothelial injury and neutrophil activation affecting other organ systems. mast cell degranulation produces vasoplegia requiring vasoconstrictors to maintain map [ ] . major complications can be broadly divided into circuitrelated and patient-related factors ( table ). the commonest mechanical complication is thrombosis within the circuit [ ] . thrombosis starts in areas of low flow and increases turbulence. clots on the arterial side of the circuit have a risk of embolization into systemic circulation and should be immediately addressed. clots on the venous side can cause coating of oxygenator and its failure [ ] . even when visible clots are absent, microthrombi and fibrin deposits on the oxygenator reduce its efficiency over time due to suboptimal gas exchange. this is more common, but not limited to long ecmo runs. air can enter into the circuit via loosely attached connectors, inadvertently open access ports or tube defects. this can be catastrophic by bringing the pump to a halt. air on the arterial side can embolize as well. in view of the critical nature of the patient subset undergoing ecmo therapy, complications can have a significant impact on outcomes [ ] . disseminated intravascular coagulation and acquired von willebrand disease are seen in patients on ecmo due to activation of the coagulation cascade with resultant consumption coagulopathy with a - % incidence of bleeding [ ] . the commonest sources of bleed are surgical and cannulation sites. intra-thoracic, intra-abdominal and intra-cranial bleeds can also occur [ ] . incidence of reopening for tamponade or haemorrhagic complications can be as high as %, paving the way for low-dose heparin protocols during the maintenance phase of ecmo [ ] . lower antithrombin iii levels are associated with higher transfusion requirements and mortality rates [ ] . replacement of blood components is based on haematocrit (hct), act, prothrombin time (pt) and aptt ratios. point-of-care testing like thromboelastography (teg) and rotational thromboelastometry allows for quick intervention and specific corrections thereby reducing risk of volume overload and inflammatory/immunological activation. the recommended target act is - s which is reduced to - s in the event of bleeding. an international normalized ratio (inr) of > . warrants correction with fresh frozen plasma, and maintaining platelet count of > , /mm is recommended. activated factor vii (viia) is used as a last measure when other modalities have failed. extreme care is exercised when viia is used and a lower dose of - μg/kg is recommended as opposed to a conventional dose of - μg/kg to avoid an inadvertent pro-thrombotic state [ ] . ufh is the anticoagulant recommended for initiating and maintaining ecmo support as per elso guidelines [ ] . heparin-induced thrombocytopenia (hit) is associated with usage of ufh. hit is an immune-mediated pro-thrombotic condition characterized by antibodies to the heparin-pf complex on platelet surfaces which induces thrombosis. it has an incidence of . - % and mortality rate of % [ ] . bivalarudin, a direct thrombin inhibitor, is an alternative anticoagulant for hit-positive patients. teg and aptt ratio are used to monitor anticoagulation [ ] . the incidence of gastrointestinal (gi) bleeding is - . % secondary to reduced gut perfusion, decreased gastric ph leading to stress ulcers and a-v malformations in the small bowel as a result of non-pulsatile flows [ ] . other contributing factors for gi bleeding include anticoagulation, coagulopathy, thrombocytopenia, platelet dysfunction, acquired von willebrand syndrome and hyperfibrinolysis. gi bleed commonly occurs around the th day of ecmo [ ] . elderly patients and need of high-volume red blood cell transfusion were associated with higher mortality [ ] . elso registry data showed high mortality from gi bleed in contrast to recent studies [ , ] . no specific guidelines for prevention of gi bleeding are available. a meta-analysis in critically ill patients showed that proton pump inhibitor prophylaxis reduces incidence of gi bleed, albeit with higher risk of ventilatorassociated pneumonia (vap) [ ] . elso guidelines recommend correction of coagulation followed by endoscopy and endotherapy. endotherapy using haemospray, fibrin glue, cyanoacrylate, cautery and clips has been used to control gi bleeding successfully [ ] . hyperbilirubinaemia and elevated liver enzymes are commonly seen in patients on ecmo and are challenging to manage due to limited therapeutic options. pre-existing liver disease can manifest as acute liver dysfunction on ecmo. when associated with cardiorespiratory problems, passive hepatic congestion can lead to chronic changes and fibrosis [ ] . the current concept of 'two hit' ischaemic liver injury happens when a liver primed by such chronic congestion experiences acute hypoperfusion causing a rapid spike in aspartate transaminase (ast) and alanine transaminase (alt) levels followed by hyperbilirubinaemia [ ] . hyperbilirubinaemia, an independent predictor of poor outcomes, occurs due to a combination of extracorporeal haemolysis and liver dysfunction [ ] . elevated alkaline phosphatase, lactate and bnp are associated with poor outcomes [ ] , while elevated ast and alt levels do not seem to be predictive. [ ] . in cases where va-ecmo was used as a bridge to heart transplant, pre-existing liver dysfunction with total bilirubin ≥ μmol/l and inr ≥ . was a predictor of mortality [ ] . similarly, a meld unos score > has also been noted to be associated with high mortality [ ] . ischaemic hepatitis and liver congestion are self-limiting, and measures which improve cardiac function can restore liver perfusion and aid recovery [ ] . molecular adsorbent recirculation system therapy may be considered in the setting of alf as it has been noted to accelerate recovery of liver function and improve survival [ ] . acute kidney injury (aki) is seen in % of patients undergoing ecmo with complex multifactorial aetiology and pathophysiology with majority of them requiring renal replacement therapy (rrt) [ ] . the most common indication for initiating rrt is to achieve fluid balance in patients unresponsive to diuretic therapy. intermittent therapies of rrt are effective in haemodynamically stable patients; however, the most common modality used is continuous rrt (crrt). a large meta-analysis has shown higher mortality when rrt was used sparingly in patients on ecmo [ ] . rrt can be provided using either an 'integrated system' or a 'parallel system'. the integrated system could be an 'in-line' haemofilter or an rrt circuit incorporated into the ecmo circuit. however, when an integrated rrt circuit is used, there is a risk of micro-clot formation within the circuit clogging the oxygenator. hence, knowledge of intra-circuit pressures, appropriate modifications in connections of the rrt circuit and additional regional anticoagulation would be necessary. on the other hand, a 'parallel system' involves a separate indwelling vascular catheter to provide rrt, obliviating the need for additional anticoagulation as patients are already anticoagulated for ecmo. close review and readjustment of prescription is crucial as per changing needs of the patient. most studies have shown that use of crrt with ecmo is not associated with increased mortality, and in fact, when used, these subset of patients needed shorter duration of ecmo. data from large ecmo centres have shown that ecmo survivors who have received rrt have similar renal outcomes with no increase in incidence of endstage renal disease in comparison to patients who did not receive rrt [ ] . neurological complications in va-ecmo are associated with high mortality and morbidity, with high incidence ( . - %) across all age groups [ ] . this has been attributed to nonpulsatile flow, low arterial o saturation in the upper half of the body and entrainment of unfiltered thrombi into the systemic circulation [ ] . risk factors associated with neurological injury in neonates are low birth weight < kg, gestational age < weeks, pre-ecmo cardio-pulmonary resuscitation (cpr), metabolic acidosis, bicarbonate use and prior ecmo exposure [ ] . neonates are more susceptible to intracranial haemorrhage (ich) ( . %) as opposed to the paediatric group ( . %) and adults ( . %) [ ] . risk factors in adults include female gender, central cannulation during cardiac surgery, thrombocytopenia, serum creatinine > . mg/dl, hypercapnia while initiating ecmo, duration of ecmo and use of anticoagulants. incidence of acute ischaemic stroke is . - % across all age groups which is multifactorial in origin [ ] . thrombocytosis at ecmo initiation is a potentially modifiable factor [ ] . brain computed tomography scan (fig. ) is the recommended imaging modality when neurological deficits are identified since magnetic resonance imaging, despite being more sensitive, is contraindicated during ecmo [ ] . use of va-ecmo is associated with a higher incidence of electrographic seizures (fig. ) in neonates ( . %) and children ( . %) as compared to adults ( . %) [ ] . nosocomial infection is a major cause of morbidity and mortality on ecmo, with an incidence of - % [ ] [ ] [ ] . the fig. non-contrast computed tomography of the brain showing rightsided intra-parenchymal haemorrhage with peri-haemorrhagic cerebral oedema and midline shift on day of starting va ecmo rate of infection was highest in adults, followed by paediatric and neonatal age groups [ , ] . it is crucial to practice meticulous infection prevention measures. longer duration of ecmo support is an independent risk factor for infection [ ] . bizzarro et al. reported a prevalence of . % in patients on ecmo > days compared to . % in patients with < days support [ ] . bloodstream infections and vap were commonly encountered [ ] . the median time interval between initiation of ecmo and occurence of a bloodstream infection was - days [ ] . these infections were predominantly caused by gram-positive organisms (coagulase-negative stapylococcus, enterococcus and staphylococcus aureus), candida and pseudomonas species [ , ] . vascular complications stem from difficult cannulation, low flow states and high use of vasoconstrictors. percutaneous cannulation techniques in peripheral va-ecmo can be associated with posterior vessel wall perforation resulting in inadequate perfusion and subsequent development of a compartment syndrome/retro-peritoneal haematoma [ ] . larger-size cannulae (> f) usage, female gender and associated peripheral vascular disease are proven risk factors [ ] . insertion of a distal perfusion cannula should be considered to augment perfusion [ ] . differential hypoxia, north-south/harlequin syndrome, occurs in peripheral va-ecmo when the heart has recovered on the backdrop of a lung still lagging behind. the peripheral ecmo cannot compete with native co, which causes poorly oxygenated blood supply to the upper half of the body while the lower half of the body receives well-oxygenated blood from the circuit [ ] . monitoring the patient's arterial saturation in the right upper limb helps in diagnosis. remedial measures include advancement of inferior vena caval cannula and delivery of oxygenated blood into the right atrium by venoarterial-venous ecmo/ hybrid circuit [ ] . the incidence of pccs va-ecmo is . % in paediatric cardiac surgery [ ] . operative stress and residual lesions added on to a physiologically compromised heart in congenital heart disease can predispose to poor cardiac function post-operatively. there is no consensus on the timing to initiate ecmo in the paediatric population. the indications and contraindications of post-cardiotomy ecmo are listed in table . oxygen extraction ratio (o er) is the ratio between oxygen consumption (vo ) and o delivery (do ). normal o er is : or %, derived from scvo . do reduces in low perfusion states. up to a certain point, tissues maintain aerobic metabolism by extracting o from blood, increasing the central venous extraction and o er. at an o er of : , there is an imbalance between metabolic demand and aerobic metabolism thereby initiating anaerobic metabolism, producing lactate and metabolic acidosis. o consumption in infants and children ( - ml/kg/min) is more in comparison to that in fig. an excerpt of continuous eeg monitoring of the patient depicted in fig. showing right hemispheric epileptic activity adults ( - ml/kg/min); hence, anaerobic metabolism and organ damage occur earlier [ ] . ufh is the mainstay for anticoagulation in children on ecmo. as hit is rare in children [ ] , the need for alternative anticoagulants seldom arises. elso guidelines [ ] suggest a bolus dose of - units/kg of ufh before cannulation and an infusion of - units/kg/h for maintenance. besides act, aptt ratio, teg, antithrombin and activated factor xa levels are used for titration of anticoagulant. transthoracic echocardiography (tte), and catheterbased diagnostic studies aid in detection of postoperative residual lesions which, when addressed, help in weaning from ecmo [ ] . the decision to vent the heart is based on tte findings. tte assists in documenting serial ventricular function improvement, identifying pericardial/ pleural effusions, assessing pulmonary hypertension and shunting at atrial or ventricular levels [ ] . all inotropes are stopped when complete myocardial rest is indicated. map targets are achieved using vasoconstrictors and vasodilators. although there is limited experience, levosimendan ( . - . mcg/kg/min for h) can be used during ecls to aid weaning [ ] . map, capillary refill time, urine output, lactate levels and scvo trends are reliable monitoring tools. a hct of % is targeted if scvo > %. in situations of do /vo mismatch/ palliated single-ventricle patients, a higher hct (> %) is targetted. gentle ventilation to achieve - ml/kg tidal volume and a peep of up to mmhg is preferred to avoid barotrauma [ ] . ecmo circuitry triggers an inflammatory response and capillary leak, causing fluid to shift out of the intravascular compartment. in the backdrop of intravascular volume depletion secondary to bleeding, patients are predisposed to prerenal aki aggravating a pre-existing hypoxic kidney injury. once volume status is normalized within - h, the capillary leak subsides and diuresis improves [ ] . treatment options for inadequate diuresis are diuretics, peritoneal dialysis (pd) and modified ultrafiltration on the circuit. rrt has not shown to improve mortality in children on ecmo [ ] . bowel hypoperfusion secondary to low co, sedative and paralytic agent usage, vasoconstrictive drugs and gut inflammation can predispose to gastric dysmotility and feed intolerance in a child on ecmo [ ] . regional gi ischaemia causes hyperlactaemia. withholding enteral feeds translocates gut bacteria thereby increasing the risk of sepsis. starting of trophic feeds once lactate has normalized is a recommended strategy [ ] . parenteral nutrition is considered when there is persistent hyperlactataemia or feed intolerance taking on board the risk of infection [ ] . severe irreversible brain injury extremely low gestational and weight (< weeks gestation or < . kg) uncontrollable haemorrhage fig. a-v bridging on ecmo consists of a circuit that runs parallel to the patient with the cannulae in situ but clamped. heparin flush is constantly circulated through the cannulae during the clamped interval to prevent clotting. if there is haemodynamic or respiratory instability, va-ecmo is recommenced by just removing the clamps on the venous and arterial cannulae the timing and sequence of weaning off ecmo is not standardized. once the myocardium shows signs of recovery, organ functions have improved and residual lesions are ruled out or corrected, full ventilatory support is commenced, inotropes started to augment cardiac contractility and ecmo flows are gradually reduced. the left-sided vent, if present, is removed when sustained ejections are seen. on further weaning to minimal ecmo flows ( ml/min), tte is done. decision is then taken to decannulate the patient. in borderline cases, a-v bridging with a trial period off ecmo ( - h) is an option. this consists of a circuit that runs parallel to the patient with the cannulae in situ but clamped (fig. ) . during a-v bridging, if there is haemodynamic or respiratory instability, va-ecmo is recommenced. if the trial period off ecmo is uneventful, the patient is decannulated [ ] . tte plays a pivotal role during various stages of weaning and in the post-wean phase [ ] . palliative surgery for univentricular hearts poses special challenges on ecmo. in infants with single ventricular physiology and systemic to pulmonary shunts, the shunt has to be partially occluded to counter pulmonary steal. the alternative is to target higher flows [ ] . the success rate for ecls, post glenn and fontan procedures is lower. the reasons are multifactorial, including complex physiology and altered cardiac anatomy, the presence of atrioventricular valve regurgitation, previous surgeries, the need for multiple drainage cannulae and the inability to achieve full flows on ecmo [ ] . success after ecmo typically is defined as survival to hospital discharge after a successful wean [ ] . for pccs va-ecmo, the average survival rate across all age groups is . % [ ] . the indicators of poor outcome have been outlined as advanced age, redo-valve surgery and climbing lactate levels. pre-operative pulmonary hypertension had no bearing on mortality [ ] . the -year survival rate was % for patients discharged from the hospital while % for patients surviving at days [ ] . discharge from hospital is the most important predictor of successful outcome [ ] . lai et al. concluded that a small percentage of patients especially in a high-volume centre would benefit from additional ecmo therapy if their cardiopulmonary function declined. additionally, a higher incidence of infection and need for rrt was reported in this subset [ ] . literature per se is nebulous about the quality-of-life predictors after ecmo. studies have shown % mortality within months of hospital discharge and this increases to % over a -year period [ ] . on the contrary, studies have depicted . % survival at months without elaborating on the quality of life [ ] . the new york heart association (nyha) class is a good tool for ascertaining functional status in ecmo survivors [ ] . functionality status of survivors have been diverse, ranging from nyha class i-iv indicating survivors can achieve a reasonable quality of life. chen et al. have reported a higher readmission rate during the first year of follow-up resulting in higher medical expenditure. infections and cardiac events were stated as common causes of mortality/morbidity in the follow-up period [ ] . literature has extensively debated on the cost-effectiveness of ecmo. several analyses have deemed ecmo to be an expensive therapy amounting to an average of $ , per case in the usa and have recommended package payments to buoy individual institutes delivering this service [ ] . in the uk, mechanical support is funded only when it has been advocated as a bridge to transplantation [ ] . there has been no such cost analysis done in the indian subcontinent. the average cost of initiating ecmo in india is meagre compared to the west. however, additional costing gets added on to patient maintenance in the icu, which could include rrt, medication, imaging, laboratory and transfusion costs. by advocating a wholesome package module, the implications of cost can be negated with the outcome benefits. from an ethical viewpoint, three perspectives have to be considered: surgeons, the patient's family and financial implications. a surgeon would look forward to successful outcomes, but, when faced with a situation of inability to wean off cpb, it is normal to consider options for recovery even if chances of successful outcome is low. the patient's family should be briefed about the condition and given an opportunity to partake in the decision-making. financial implications of ecmo need be explained as healthcare in india is not funded. though the cost of initiation of ecmo is finite, duration and end-point are difficult to ascertain and costs are impractical to calculate. there are situations where hospitals or other payers like insurance will meet the additional expense, but that is the exception rather than the rule. these nuances should be discussed and documented to enable the family to make an informed decision. counselling and communication is key to supporting the family through this tumultuous phase. va-ecmo has made inroads into the management of pccs in india. bearing its cost implications, it has yet to make a significant impact in the management of these subset of patients. at narayana institute of cardiac sciences (nics), bangalore, india, we on an average perform about - ecmo runs a year, a majority of which are post-cardiotomy ecmo runs. considering the factors influencing cannulation, our institutional preference is the central route. if the patient presents with pccs, our cannulation sites are the right atrial appendage and the ascending aorta close to the sino-tubular junction. we have observed harlequin syndrome in those patients with high aortic cannulation, and these patients presented with persistent ventricular fibrillation and altered sensorium. this was due to deoxygenated blood from the lv selectively streaming into coronaries and the right innominate artery. this was promptly reversed by changing to a lower cannula position. cannulae are snugged using rubber spigots, following which they are tunnelled sub-xiphoid and chest closed with sternal wires. absolute haemostasis is imperative. a common bleeding point is the aortic cannulation site. for this, rows of purse strings are used that encompass the cannula twice causing a cuff of adventitia to evert around the cannula to stop further bleeding. for lv venting, our strategy is to cannulate the lv apex directly with a separate limb to the inflow circuit (fig. ) . we keep a dedicated flow sensor on this limb to detect low flow. an obvious disadvantage of this is formation of a lv clot around the cannula inflow. this is prevented by maintaining a higher aptt ratio and using a larger-sized cannula. the decision to vent the left heart is based upon the disappearance of ejections on the arterial trace, presence of spontaneous echo contrast on tee, inadequate flows with obvious signs of lv distention and to prevent harlequin syndrome in peripheral cannulation. we strongly believe in central cannulation for the following reasons: at our institute, the weaning process starts in the icu and the final stage happens in the or under tee guidance. the patient is primed with levosimendan overnight without a loading dose. the ventilator is adjusted for optimal gas exchange. haemodynamic variables are monitored using echocardiography and a pulmonary artery catheter. metabolic stability is monitored by trends in lactate level, base excess in arterial gases and scvo monitoring. anticoagulation is maintained with aptt - s or act - s. flows are reduced by . l/min every nd hourly till a flow of % is achieved. if a lv vent is in situ, a gated clamp regulates the lv vent flows. flows are reduced in aliquots of ml every second hour till a flow of ml is reached. the patient is idled at this flow till transfer to the or for final wean and decannulation. weaning is aborted at any stage if there is ventricular distension, increase in inotropic levels to maintain haemodynamics, worsening gas exchange or metabolic parameters. we performed a total of , cardiac surgeries in and . pccs va-ecmo was instituted in ( . %) of these patients. our results are broadly outlined in table . bleeding was a significant problem. major transfusions were needed in the initial -h period. the transfusion requirements were monitored with th hourly clotting screens and teg. the incidence of aki with rrt requirements were comparable across age groups which is similar to published data [ ] . our preference for instituting rrt is using a parallel circuit to prevent possible air embolism. rrt in the paediatric patients was provided by pd. a rising trend of total bilirubin was associated with failure to wean and mortality. overall mortality of ecmo patients with limb ischaemia was . %. literature has shown higher incidence of neurological [ ] [ ] [ ] in contrast to our data. the incidence of gi bleed in our cohort was . % which compares favourably with published data [ , ] . better weaning results were observed between and (table ) a review of the bloodstream infections in patients on pccs va-ecmo revealed a predominance in gramnegative bacilli (gnb) ( %), followed by candida species ( %) and gram-positive organisms ( %). klebsiella species constituted the majority of the gnb bacteraemias. carbapenem resistance was present in % of the gramnegative organisms isolated ( % carbapenem resistance in klebsiella species alone). most of the blood culture isolates grew within the first h of incubation. however, % of the organisms grew only after days of incubation, highlighting the 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experience of cases outcomes of venoarterial extracorporeal membrane oxygenation patients requiring multiple episodes of support longterm survival in adults treated with extracorporeal membrane oxygenation for respiratory failure and sepsis long-term prognosis after extracorporeal life support in refractory cardiogenic shock -results from a real-world cohort patients' self-assessed functional status in heart failure by new york heart association class: a prognostic predictor of hospitalizations, quality of life and death long-term outcomes of extracorporeal membrane oxygenation support for postcardiotomy shock financial and clinical outcomes of extracorporeal mechanical support the comparative use of ventricular assist devices: differences between europe and the united states publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgements we would like to acknowledge the help and insights provided by dr. julius punnen, dr. varun shetty, dr. rammohan sripad bhat, dr. vijay samuel richard, dr. rangarajan kasturi, dr. radhika manohar, dr. shrinivas hittalamani and dr. anup daniel varghese who are specialists in their fields in writing this document. we would also like to mention the assistance provided by mr. selvakumar, senior key: cord- -mkzw nya authors: le guennec, loïc; shor, natalia; levy, bruno; lebreton, guillaume; leprince, pascal; combes, alain; dormont, didier; luyt, charles-edouard title: spinal cord infarction during venoarterial-extracorporeal membrane oxygenation support date: - - journal: j artif organs doi: . /s - - - sha: doc_id: cord_uid: mkzw nya spinal cord infarction (sci) is a rare disease among central nervous system vascular diseases. only a little is known about venoarterial extracorporeal membrane oxygenation (va-ecmo)-related sci. retrospective observational study conducted, from to , in a tertiary referral center on patients who developed va-ecmo-related neurovascular complications, focusing on sci. during this period, among the patients requiring va-ecmo support, ( . %) developed an ecmo-related neurovascular injury: ( . %) ischemic strokes, ( . %) intracranial bleeding, one cerebral thrombophlebitis ( . %) and ( . %) spinal cord infarction. herein, we report a series of six patients with refractory cardiogenic shock or cardiac arrest receiving circulatory support with va-ecmo who developed subsequent sci during ecmo course, confirmed by spine mri after ecmo withdrawal. all six patients had long-term neurological disabilities. va-ecmo-related sci is a rare but catastrophic complication. its diagnosis is usually delayed due to sedation requirement and/or icu acquired weakness after sedation withdrawal, leading to difficulties in monitoring their neurological status. even if no specific treatment exist for sci, its prompt diagnosis is mandatory, to prevent secondary spine insults of systemic origin. based on these results, we suggest that daily sedation interruption and neurological exam of the lower limbs should be performed in all va-ecmo patients. large registries are mandatory to determine va-ecmo-related sci risk factor and potential therapy. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. spinal cord infarction (sci) is a rare disease among central nervous system vascular diseases. causes of sci can be idiopathic ( %), degenerative spine disease ( . %), associated to aortic pathology with or without surgery ( . %), epidural anesthesia ( . %), arteriosclerosis ( . %), cardiac embolism ( . %), or secondary to an acute systemic hypoperfusion ( . %) [ ] . it is often associated with severe prognosis and permanent sequelae [ , ] . coronary angiography and intra-aortic balloon pump (iabp) may cause sci [ ] [ ] [ ] , as well as venoarterial-extracorporeal membrane oxygenation (va-ecmo). this latter condition has only been reported as small case series; one patient with refractory cardiac arrest due to myopericarditis [ ] , and a short case series of three patients with a combination of va-ecmo and iabp [ ] . these sci were documented by mri after circulatory support withdrawal, and multifactorial origin was retained by the authors to explain the pathophysiological process that led to ischemia (hypoperfusion, vasoconstriction, thromboembolism of adamkiewicz artery, etc.…). in this study, we retrospectively identified in our database six cases of sci (documented by mri) after va-ecmo (± iabp) withdrawal, and discussed its potential risk factors. characteristics of patients are resumed in table . intracranial bleeding, cerebral thrombophlebitis ( . %) and ( . %) spinal cord infarction. anticoagulation protocol, membrane oxygenator and its circuitry management are reported in the appendix (online supplement). anticoagulation was performed according to this protocol in all patients. patients were sedated with propofol infusion. a -year-old man presented with refractory cardiac arrest after cocaine consumption. va-ecmo was inserted during chest compression (no-and low-flow duration of and min, respectively). coronary angiography was normal. patient's cardiac condition improved rapidly, and va-ecmo was removed on day . since the patient required prolonged sedation, the first neurological assessment was performed on day . at that time, he was found to have a normal sensory examination, but suffered from icu acquired weakness. seven weeks later, motor strength improved at the upper limbs, but because of lower limbs weakness persistence, a spinal cord mri (fig. a, b) was performed, days after va-ecmo withdrawal. a longitudinal anterior high t -weighted signal with owl-eyes sign extending from t to the conus medullaris was observed, consistent with anterior spinal artery infarction. after extubation, the patient was discharged from icu at day . at -year follow-up, patient had to use wheelchair and to catheterize his own urinary tract to manage the neurogenic bladder. a -year-old man presented with septic shock and acute respiratory distress syndrome due to pneumococcal pneumonia. echocardiography showed severe biventricular dysfunction, with left ventricular ejection fraction of %. he developed refractory cardiogenic shock, and va-ecmo was placed. coronary angiogram showed no abnormality, and diagnosis of septic cardiomyopathy was retained. cardiac condition started to improve at day and va-ecmo was removed on day . a few minutes after va-ecmo removal, the patient presented cardiac arrest. va-ecmo was reimplanted. patient was extubated on day and suffered icu acquired weakness. his cardiac condition slowly improved, and month later, va-ecmo was removed. motor strength started to improve within the upper limbs, with persistence of lower limbs sensorimotor deficiency. spinal cord mri (fig. c, d) was performed, which showed a longitudinally extensive anterior high t -weighted signal extending from t to the conus medullaris, confirming sci diagnosis. oneyear follow-up showed no neurologic recovery. patient was always awake without sedation icu intensive care unit, va-ecmo venoarterial-extracorporeal membrane oxygenation, saps simplified acute physiology score, sofa sequential organ-failure assessment, sci spinal cord infarction, iabp intra-aortic balloon counterpulsation, aptt activated partial thrombin time, na not applicable, nk not known a -year-old man had refractory cardiac arrest complicating acute myocardial infarction. implantation of va-ecmo was performed during chest compression (no-and low-flow duration of and min, respectively). coronary angiography showed occlusion of the circumflex and right coronary arteries, which were successfully stented. va-ecmo was removed on day . after sedation withdrawal on day , patient was alert and weaned from mechanical ventilation. he displayed a sensorimotor impairment of the lower limbs. spinal cord mri (fig. e, f) showed a t -signal abnormality confined to anterior horns extending from t to the conus medullaris consistent with anterior spinal artery infarction. one-year follow-up showed no neurologic recovery. a -year-old man with medical history of ischemic dilated cardiomyopathy was admitted to icu for cardiogenic shock. despite optimal medical therapy, his condition worsened and he underwent heart transplantation few days later. due to primary heart graft dysfunction and inability to wean off cardiopulmonary bypass during surgery, va-ecmo was inserted. the patient received sedatives and the first neurological assessment was performed on day . he was alert but suffered from icu acquired weakness. patient's cardiac condition progressively improved, and va-ecmo was removed on day . one week later, he started to regain motor function, but only within the upper limbs, with lower limbs proprioceptive deficit. spinal cord mri (fig. g, h) was performed days after va-ecmo withdrawal, showing a longitudinally extensive posterior intramedullary hight weighted signal extending from t to the conus medullaris. ten days after va-ecmo withdrawal, the patient suffered from a new ventilator-associated pneumonia with septic shock, and died of refractory multiorgan failure. a -year-old man presented with acute myocardial infarction. coronary angiography showed proximal left anterior descending artery occlusion, that was successfully stented. because of refractory cardiogenic shock, va-ecmo and were inserted. cardiac condition improved on day , and both va-ecmo/iabp were removed on day . after sedation withdrawal on day , he was alert and weaned from mechanical ventilation. neurological examination revealed weakness of the lower limbs. spinal cord mri (fig. i , j) showed a longitudinally extensive anterior hypert weighted signal within the conus medullaris. at -year follow-up, patient was moving in wheelchair. a -year-old man with medical history of ischemic dilated cardiomyopathy was admitted to the icu for cardiogenic shock. despite medical therapy, his condition worsened and va-ecmo was inserted with concomitant iabp. patient was scheduled for heart transplantation. seven days after va-ecmo/iabp start, he had pain in the lower limb, with sensory abnormalities during neurological examination, but without any motor weakness. he underwent heart transplantation on day after va-ecmo/iabp initiation, but due to primary graft dysfunction and the inability to wean off cardiopulmonary bypass, va-ecmo was left in place. on day post heart transplantation, iabp was removed and mechanical ventilation was weaned. va-ecmo was removed on day ( days after heart transplantation). thirty-seven days after va-ecmo withdrawal, since no neurological change was observed regarding the lower limbs sensory abnormalities, and a spinal cord mri was performed (fig. k, l) . it showed a longitudinally extensive posterior t -weighted signal abnormality extending from t to the conus medullaris. at -month follow-up, patient still had pain in the lower limbs. we described here the largest case series of va-ecmorelated sci patients. medullary infarction is a rarely described complication of va-ecmo support [ , ] , with only four cases in the literature. however, va-ecmo was not the only risk factor for ischemic events in our patients; coronary angiography, iabp use and low cardiac output consecutive to heart failure/cardiac arrest may also be responsible for sci. thus, it is difficult to assess the respective impact of underlying disease(s) and va-ecmo itself. however, ecmo might play a role, regarding the high rate of systemic thromboembolic events in this population [ ] . sci is usually suspected on clinical examination. as shown in four of our six cases, late awakening and severe critical illness polyneuropathy may delay its diagnosis. because only awake patients with clinical symptoms who were explanted of their va-ecmo underwent spine mri, we perhaps may have missed some events in other patients. indeed, as it is difficult to neurologically assess patients with severe disability after cardiac arrest-related brain injury, simultaneous sci could have potentially remained unidentified in this population. moreover, patients who died under va-ecmo and remained sedated during their icu stay might have been undiagnosed. lastly, as shown with patient , atypical presentation with isolated sensory deficit can delay sci diagnosis. the pathogenesis of sci following va-ecmo remains unclear. prolonged hypoperfusion can cause spinal cord ischemia [ ] . another mechanism described in autopsy reports is small arterioles occlusion by cholesterol or atheromatous emboli [ , , ] , that could results from aortic atheroma disruption and fragmentation during va-ecmo/ iabp implantation or coronary angiography, but also during withdrawal of the former, with subsequent occlusion of small vessels. as a matter of fact, this mechanism has been previously described in patients with iabp alone [ ] [ ] [ ] [ ] . in our patients, sci could have been consecutive to multiple injuries or different injury from one patient to another, such as mechanical trauma and/or arterial embolism of a spinal artery caused by the ecmo itself, coronary angiography or iabp, prolonged hypoperfusion and/or vasopressor use being precipitating, aggravating or triggering factors. to the best of our knowledge, no large study evaluating sci treatment has been published to date. however, prevention of secondary neurologic damage (i.e., hypotension, fever, etc.), antiplatelet therapy and steroids are usually given [ , ] . removal of the potential cause of sci (va-ecmo and/or iapb), when possible, could be part of the treatment, as one case of neurological medullary improvement after iabp removal have been reported [ ] . finally, the most important issue is the rehabilitation program; for patient education, bladder management, and occupational therapy. va-ecmo-related sci is a rare but catastrophic complication, with high rate of long-term neurological disabilities. even if neurological examination is difficult in sedated patients or in patients with critical illness polyneuropathy, regular neurologic examinations of lower limbs should be performed for prompt sci diagnosis and prevent secondary spine insults of systemic origin. spinal cord infarction: prognosis and recovery in a series of patients long-term outcome of acute spinal cord ischemia syndrome a rare but serious complication of percutaneous coronary intervention: spinal cord embolism paraplegia as a result of intra-aortic balloon counterpulsation paraplegia caused by aortic dissection after intraaortic balloon pump assist a case of fulminant perimyocarditis leading to extensive ecmo treatment and spinal injury resulting in paraplegia spinal cord infarct during concomitant circulatory support with intra-aortic balloon pump and veno-arterial extracorporeal membrane oxygenation brain injury during venovenous extracorporeal membrane oxygenation ischemic and hemorrhagic brain injury during venoarterial-extracorporeal membrane oxygenation autopsy findings in patients on postcardiotomy extracorporeal membrane oxygenation (ecmo) thoracic spinal cord ischemia following acute myocardial infarction and cardiac arrest in a young male spinal cord infarction following intraaortic balloon support spinal cord infarction due to cholesterol emboli complicating intra-aortic balloon pumping (case report and review of the literature) possible intra-aortic balloon pump "functionrelated" mechanism of embolic events in patient with protruding atheroma in the thoracic aorta intra-aortic balloon pump related thrombus in the proximal descending thoracic aorta with peripheral emboli paraplegia due to spinal cord infarction after coronary artery bypass graft surgery acute spinal cord ischemia during aortography treated with intravenous thrombolytic therapy thrombolysis in anterior spinal artery syndrome paraplegia associated with intraaortic balloon pump counterpulsation key: cord- - gge e authors: yusuff, hakeem; zochios, vasileios; brodie, daniel title: thrombosis and coagulopathy in covid- patients requiring extracorporeal membrane oxygenation date: - - journal: asaio j doi: . /mat. sha: doc_id: cord_uid: gge e nan the coronavirus disease (covid- ) pandemic has challenged intensivists caring for patients with severe respiratory disease, associated multiorgan dysfunction, and high mortality. extracorporeal membrane oxygenation (ecmo) has been used to manage patients with covid -associated severe respiratory or cardiac failure with mortality in excess of %. , a significant feature of this disease appears to be an excess of thrombosis and there have been reports of an incidence of more than % of intensive care unit (icu) admissions. the etiology of thrombosis in this setting may be closely linked with the hyperinflammatory response of the immune system when exposed to severe acute respiratory syndrome coronavirus- (sars-cov- ). in addition, there is early development of a disseminated intravascular coagulation (dic)-like picture in a subset of patients, the management of which is made more complicated if providing systemic anticoagulation to prevent thrombosis and maintain the extracorporeal circuit. the purpose of this editorial is to briefly discuss covid- -associated procoagulant and anticoagulant states in the context of ecmo support. sars-cov- infection shares pathophysiological characteristics with other coronaviruses (severe acute respiratory syndrome and middle east respiratory syndrome). the initial manifestation of the infection is characterized by endotheliopathy and pulmonary vascular microthrombosis, which may present with hypoxemia and a need for oxygenation or ventilatory support. endotheliopathy activates two independent molecular pathways: inflammatory and microthrombotic. [ ] [ ] [ ] [ ] the former pathway triggers the release of inflammatory cytokines and the latter promotes exocytosis of unusually large von willebrand factor multimers (ulvwf) and platelet activation. the inflammatory pathway initiates inflammation, but the microthrombotic pathway produces "microthrombi strings" composed of platelet-ulvwf complexes, which become anchored on the injured endothelial cells and trigger disseminated intravascular microthrombosis. [ ] [ ] [ ] [ ] high plasma levels of proinflammatory cytokines (interleukin- , , , and , granulocyte colony-stimulating factor and tumor necrosis factor-α) have been observed in covid- patients admitted to icu. this is consistent with, although not diagnositic of, a "cytokine storm" associated with the secondary development of a hemophagocytic lymphohistiocytosis. this contributes to fibrinogen generation and an overwhelming of the profibrinolytic pathway causing increased expression on plasminogen activator inhibitor- . a recent postmortem evaluation of covid- patients reported the presence of diffuse alveolar damage and fibrin-platelet thrombi in small arteries in the lungs and other organs. however, the generalizability of these findings to a wide range of covid- patients is unclear. this initial prothrombotic insult and inflammation in combination with other risk factors including immobility, obesity, and hypovolemia may contribute to an increased incidence of arterial and venous thromboembolism. there are reports of deep vein thrombosis, pulmonary emboli, ecmo cannula, and circuit thrombosis and ischemic strokes among others. , this could potentially have a contributory effect on the severity of respiratory failure and consequently multiorgan failure. a lack of resolution of the widespread thrombi may be an important factor in the prognosis of covid- patients in icu and various studies in patients with covid- have consistently shown a strong association between elevated d-dimer levels and adverse overall outcomes. , although this association is real, it remains uncertain whether the mechanistic explanation of the links between elevated d-dimer levels and outcomes in this context is increased fibrin generation and degradation or hyperinflammation. , , the extracorporeal circuit, covid- , and bleeding covid- -associated coagulopathy (cac) has been recently described and shares similarities with classic dic. the degree of activated partial thromboplastin time elevation in cac is often less than prothrombin time (pt) elevation (likely due to elevated factor viii levels), thrombocytopenia is usually mild (approximately × /l), and microangiopathy is not present. , in most patients, overt bleeding is not evident with only mild derangements in the usual laboratory tests of coagulation, which do not fulfil usual clinical definition of coagulopathy. however, the patients with the worst outcomes have early coagulopathy, raised pt, and increased d-dimer. a review of the coagulation profile of hospitalized patients revealed a median onset of dic at days in over % of the nonsurvivors while only of the survivors had evidence of dic. one of the most common late complications of ecmo support in covid- patients is bleeding, which has been associated with poor outcomes, albeit with very limited data. , given the context described above, it is possible that any coagulopathy associated with the extracorporeal circuit would have a synergistic effect with cac, although there is currently little evidence to support this. the initial effect of establishing ecmo creates an overall procoagulant effect. , there is contact activation of the coagulation cascade, thrombin generation, and fibrin deposition on the artificial surfaces. , there is also an inflammatory response at initiation of extracorporeal support, which leads to upregulation of prothrombotic pathways and, to a lesser degree, the fibrinolytic pathways. [ ] [ ] [ ] [ ] [ ] this underscores the role of anticoagulation in maintaining circuit patency; however, given the dynamic nature of the extracorporeal support, the coagulation state is also dynamic. as the ecmo support proceeds, the anticoagulant factors have an increased influence due to loss of large-molecule von-willebrand factor and decreased platelet adhesion (due to glycoprotein b and glycoprotein vi loss), which may increase bleeding risk. [ ] [ ] [ ] [ ] in addition, there is consumption of coagulation factors and reduction in the effect of contact activation over time as protein adsorption to the artificial surfaces develops. in most patients, the procoagulant effects predominate hence the need for continued anticoagulation. it is well established that the significant inflammation associated with sepsis can alter this balance by initially producing an aggravated prothrombotic response at the start of extracorporeal support with consequent rapid transition to an anticoagulant state, characterized by a dic-type picture and hyperfibrinolysis (figure ) . this state is associated with an increased risk of death. the hyperinflammatory state associated with covid- disease may create these effects as well, potentially contributing to hemorrhagic complications encountered during ecmo support. hemorrhage in this context is very difficult to manage as the circuit remains prothrombotic while the patient is bleeding. given the complex nature of this problem, early consultation with hematology may be prudent as part of a multidisciplinary team approach. this effect has practical implications when caring for covid- patients requiring ecmo support. the varying and dynamic heparin requirements can be difficult to monitor and manipulate. thrombotic complications such as acute pulmonary embolism, ecmo cannula thrombosis and oxygenator thrombosis have been reported in covid- patients requiring ecmo. higher rates of bleeding are encountered when procedures are carried out with attendant increased use of blood products. some have suggested that planned invasive procedures (e.g., percutaneous tracheostomy) should be performed in the early procoagulant phase, preferably in the first - hours of the ecmo run, especially in patients with early evidence of cac. however, evidence for this is lacking. in the case of necessary emergency procedures, the increased risk of bleeding and its effect on outcomes must be strongly considered when making a risk-to-benefit judgment, especially in patients who are late into their ecmo support. covid- presents with a hyperinflammatory immune reaction in patients requiring intensive care and extracorporeal support. the associated increased risk of thrombosis and coagulopathy in ecmo patients is a result of a combination of processes driven by the disease occurring in synergy with the effect of the extracorporeal circuit on the coagulation system. large-scale prospective data on hemorrhagic and thrombotic complications in the covid- patient population requiring ecmo support may provide insights into these pathophysiological processes and the effective management strategies. ongoing analysis of the extracorporeal life support organization registry data and data from ecmo centers around the world (extracorporeal membrane oxygenation for novel coronavirus acute respiratory disease (ecmocard study) will hopefully help to better characterize and understand these pathologic derangements of coagulation. asian critical care clinical trials group: intensive care management of coronavirus disease (covid- ): challenges and recommendations initial elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure ecmo in covid- : extracorporeal life support organization incidence of thrombotic complications in critically ill icu patients with covid- thrombocytopenia in critically ill patients due to vascular microthrombotic disease: pathogenesis based on "two activation theory of the endothelium sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease acute respiratory distress syndrome as an organ phenotype of vascular microthrombotic disease: based on hemostatic theory and endothelial molecular pathogenesis diagnosis, prevention, and treatment of thromboembolic complications in covid- : report of the national institute for public health of the netherlands high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study post-mortem examination of covid patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction china medical treatment expert group for covid- : clinical characteristics of coronavirus disease in china japanese association for acute medicine disseminated intravascular coagulation study group: predicting the severity of systemic inflammatory response syndrome (sirs)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers covid- and its implications for thrombosis and anticoagulation abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia prognosis when using extracorporeal membrane oxygenation (ecmo) for critically ill covid- patients in china: a retrospective case series current understanding of how extracorporeal membrane oxygenators activate haemostasis and other blood components multi-modal characterization of the coagulopathy associated with extracorporeal membrane oxygenation ecmo and anticoagulation: a comprehensive review activation of hemostasis after coronary artery bypass grafting with or without cardiopulmonary bypass contact system revisited: an interface between inflammation, coagulation, and innate immunity mechanical circulatory support is associated with loss of platelet receptors glycoprotein ibα and glycoprotein vi extracorporeal life support: the precarious balance of hemostasis early changes in coagulation profiles and lactate levels in patients with septic shock undergoing extracorporeal membrane oxygenation ecmo for covid- associated severe ards and risk of thrombosis percutaneous tracheostomy on veno-venous extracorporeal membrane oxygenation: balancing the risk of bleeding with thrombosis extracorporeal life support organization key: cord- -yhnpskb authors: kasai, takehiko; bunya, naofumi; wada, kenshiro; kakizaki, ryuichiro; mizuno, hirotoshi; inoue, hiroyuki; uemura, shuji; takahashi, satoshi; narimatsu, eichi; takeda, shinhiro title: veno‐venous extracorporeal membrane oxygenation and prone ventilation for therapeutic management of covid‐ date: - - journal: acute med surg doi: . /ams . sha: doc_id: cord_uid: yhnpskb background: the efficacy and safety of the combined use of veno‐venous extracorporeal membrane oxygenation (ecmo) and prone ventilation are currently not known for coronavirus disease (covid‐ ). case presentation: we report two cases in which the combination of veno‐venous ecmo and prone ventilation for severe acute respiratory syndrome coronavirus (sars‐cov‐ ) pneumonia were successfully carried out. both patients had developed severe respiratory failure due to sars‐cov‐ pneumonia, thus requiring veno‐venous ecmo. prone ventilation was also administered safely. conclusion: oxygenation and lung compliance gradually improved during prone ventilation, and both patients were successfully extubated. for patients with severe sars‐cov‐ pneumonia who require veno‐venous ecmo, the use of prone ventilation could be beneficial, and should be considered. a t the end of , acute respiratory disease caused by the severe acute respiratory syndrome coronavirus (sars-cov- ) began to spread in wuhan, china. this respiratory illness, named coronavirus disease (covid- ), gradually spread globally, and the who declared covid- as a pandemic in march . prone ventilation has been reported to reduce mortality among patients with moderate-to-severe acute respiratory distress syndrome (ards) when used for at least h daily. furthermore, veno-venous extracorporeal membrane oxygenation (ecmo) is the standard treatment for severe ards. however, the efficacy of the combination of venovenous ecmo and prone ventilation is currently not known. here, we report two cases in which the combination of veno-venous ecmo and prone ventilation was successful in treating sars-cov- pneumonia. a -year-old man with a history of hypertension, diabetes, and chronic atrial fibrillation was admitted to a local hospital days after developing a fever and tested positive for the sars-co-v- . fourteen days after the onset of symptoms, his respiratory status deteriorated, and he was intubated. two days later, he was referred to our hospital to receive veno-venous ecmo. the patient's vital signs on admission to our hospital were as follows: respiratory rate, breaths/min; oxygen saturation, % under positive end-expiratory pressure (peep) of cmh o and fraction of inspiratory oxygen (fio ) of . ; heart rate, b.p.m.; and blood pressure, / mmhg using noradrenaline . lg/kg/min and vasopressin units/h. the arterial blood gas analysis results were: ph . ; pao , . ; and paco , . . laboratory data showed elevation of n-terminal pro-brain natriuretic peptide ( , pg/ml) and creatinine ( . mg/dl). left ventricular ejection fraction was % by echocardiogram and the daily urine output was approximately ml. hypoxia due to heart failure or renal failure was also considered, but we determined that sars-cov- pneumonia was the leading cause of hypoxia. therefore, we decided to treat with venovenous ecmo and continuous renal replacement therapy. veno-venous ecmo was administered through the right internal jugular vein for blood drainage with a french gauge (fr) heparin-coated cannula, and the right femoral vein for blood return with a fr heparin-coated cannula. the procedure was carried out safely, and the patient experienced no complications. computed tomography (ct) showed bilateral ground-glass opacities and bilateral dorsal consolidation (fig. ) . after hemodynamic stabilization, prone ventilation was implemented safely from day to day (prone position for h, supine position for h). the patient's pao and lung compliance were gradually improved within h of prone ventilation: pao from . to . mmhg; and lung compliance from ml/cmh o to ml/cmh o. the use of ecmo was stopped on day ( table ) . the patient was extubated on day . emergency medical services found a -year-old woman collapsed at her home. she was lethargic, and her blood pressure could not be measured. on arrival at our hospital, her vital signs were as follows: consciousness, glasgow coma scale of (e v m ); respiratory rate, breaths/min; oxygen saturation, % with reservoir face mask at l/min oxygen; blood pressure, / mmhg; heart rate, b.p.m.; and body temperature, . °c. the patient's laboratory data were as follows: hematocrit, . %; n-terminal pro-brain natriuretic peptide, , pg/ml; creatinine, . mg/dl. the ct imaging revealed bilateral ground-glass opacities, and the patient tested positive for sars-cov- . the patient had a medical history of diabetes and depression. the day after admission, the patient's respiratory status had deteriorated, and she was intubated. the arterial blood gas analysis on day was as follows: ph, . ; pao , . ; and paco , . (fio . , peep cmh o). the ratio of arterial oxygen partial pressure to the fractional inspired oxygen was at . and continued to decrease gradually. the patient's blood pressure was / mmhg using noradrenaline . lg/kg/min and vasopressin units/ h. left ventricular ejection fraction was % by echocardiogram and the daily urine output was approximately ml. we decided to treat the patient with ecmo. the veno-venous ecmo was established through the right internal jugular vein for blood drainage with a fr heparin-coated cannula, and the right femoral vein for blood return with a fr heparin-coated cannula. the procedure was carried out safely, and no complications occurred. the ct imaging showed a deteriorating bilateral dorsal consolidation (fig. ) . prone ventilation was administered safely from day to day . the patient's pao and lung compliance were gradually improved within h of prone ventilation: pao from . to . mmhg and lung compliance from to ml/cmh o. the veno-venous ecmo treatment was stopped on day ( table ) . the patient was extubated on day . t he guidelines for the management of covid- in mechanically ventilated adult patients with refractory hypoxemia by the society of critical care medicine and the european society of intensive care medicine suggest the use of veno-venous ecmo. the guidelines also state optimizing the ventilation and using prone ventilation for moderate-to-severe ards. there is no recommendation for a therapeutic combination of veno-venous ecmo and prone ventilation. our cases show that prone ventilation is possible even when using veno-venous ecmo. the advanced critical care and emergency center at sapporo medical university is a referral center for adult patients requiring ecmo in hokkaido, japan. the center has six beds in the intensive care unit and full-time doctors. we treat approximately cases of respiratory ecmo annually. in a report of radiological date from patients with covid- pneumonia, ct images showed that covid- pneumonia was manifested with chest abnormalities, even in asymptomatic patients, with a rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities, that progressed to or coexisted with consolidations within - weeks. therefore, prone ventilation is likely to be effective in gradually decreasing the ventral alveolar distension and dorsal alveolar collapse in covid- cases. in our cases, ct images after veno-venous ecmo placement showed bilateral dorsal consolidation. these findings suggest that prone ventilation could be beneficial. there are two main safety concerns related to the use of combined veno-venous ecmo and prone ventilation for covid- treatment. the first concern is tube displacement. this problem has been discussed both in veno-venous ecmo combination therapy and prone ventilation. as the blood drainage cannula and blood return cannula of ecmo have a large diameter, in the event of displacement, the risk of a fatal bleeding complication increases. additionally, displacement could also be fatal due to the use of a discontinued ecmo machine. however, the application of prone ventilation during veno-venous ecmo has been shown to be a safe and reliable technique when undertaken in an ecmo center by trained staff and following standard procedures. the second concern is the spread of sars-cov- as a result of an accidental disconnection of the intubation tube from the ventilator. there is a possibility that the virus persists through aerosol for a substantially long period, rendering the medical personnel at risk of infection. therefore, the disconnection of the intubation tube from the ventilator must be minimized. in order to address these concerns, we assigned qualified personnel to manage the connection between the intubation tube and the ventilator and the blood drainage and return cannulas in veno-venous ecmo when patients were shifted from the spine to prone position. there was no tube displacement in either case, and the risk of spreading sars-cov- was minimized. we have used airfluidized bed when patients were shifted from the spine to prone position. by using air-fluidized bed, the shift from the spine to prone position can be carried out by four medical staff. in conclusion, the combination therapy of veno-venous ecmo and prone ventilation is possible in patients with sars-cov- pneumonia without any complication. for severe sars-cov- pneumonia requiring ecmo, prone ventilation could be useful, as evidenced by radiographic data. prone ventilation should be considered for use by medical personnel. clinical characteristics of coronavirus disease in china prone position for acute respiratory distress syndrome. a systematic review and meta-analysis venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study application of prone position in hypoxaemic patients supported by veno-venous ecmo aerosol and surface stability of sars-cov- as compared with sars-cov- acknowledgements w e thank japan ecmonet for covid- for advice on ecmo management. we would also like to thank editage for their english language editing services. approval of the research protocol: formal ethical approval from the university research ethics board was not required for the completion of this study.informed consent: written informed consent for publication of this case report was obtained from the patients. registry and registration no. of the study: n/a. animal studies: n/a. conflict of interest: none. key: cord- -dxk i t authors: papa, joey c.; stolar, charles j. h. title: extracorporeal membrane oxygenation date: journal: pediatric surgery doi: . / - - - - _ sha: doc_id: cord_uid: dxk i t extracorporeal membrane oxygenation (ecmo) is a life-saving technology that uses partial heart and lung bypass for extended periods. it is not a therapeutic modality, but rather a supportive tool that provides suf-fi cient gas exchange and perfusion for patients with acute, reversible cardiac or respiratory failure. this affords the patient's cardiopulmonary system time to rest, sparing them from the deleterious effects of traumatic mechanical ventilation and perfusion impairment. the extracorporeal life support organization (elso) was formed in by a collaboration of physicians, nurses, perfusionists, and scientists with an interest in ecmo. the group provides an international registry that collects data from almost all ecmo centers in the united states and throughout the world. at the end of , elso registered nearly , neonatal and pediatric patients treated with ecmo for a variety of cardiopulmonary disorders with an overall survival rate of %. extracorporeal membrane oxygenation (ecmo) is a life-saving technology that uses partial heart and lung bypass for extended periods. it is not a therapeutic modality, but rather a supportive tool that provides suffi cient gas exchange and perfusion for patients with acute, reversible cardiac or respiratory failure. this affords the patient's cardiopulmonary system time to rest, sparing them from the deleterious effects of traumatic mechanical ventilation and perfusion impairment. the extracorporeal life support organization (elso) was formed in by a collaboration of physicians, nurses, perfusionists, and scientists with an interest in ecmo. the group provides an international registry that collects data from almost all ecmo centers in the united states and throughout the world. at the end of , elso registered nearly , neonatal and pediatric patients treated with ecmo for a variety of cardiopulmonary disorders with an overall survival rate of %. neonates are the patients who benefi t most from ecmo. cardiopulmonary failure in this population can arise from meconium aspiration syndrome (mas), congenital diaphragmatic hernia (cdh), persistent pulmonary hypertension of the newborn (pphn), as well as several congenital cardiac diseases. for the pediatric population, the most common disorders treated with ecmo are bacterial and viral pneumonia, acute respiratory failure, ards, sepsis, and cardiac disease. the experience with pediatric cardiac ecmo has been increasing over the past few years. its use for treating postcardiotomy patients who are unable to wean from bypass as well as cardiac failure with bridge to transplantation have expanded greatly in the last decade. some indications for ecmo that are not yet established clinically include emergency cardiopulmonary bypass and ecmo during cpr (ecpr) respiratory failure second to mediastinal compression (mass effect), smoke inhalation, severe asthma, or rewarming of hypercoagulopathic and hypothermic trauma patients (see fig. . ). the selection of patients as potential ecmo candidates continues to remain controversial. the selection criteria are based on data from multiple institutions, patient safety, and mechanical limitations related to equipment. the risk of performing an invasive procedure that requires systemic heparinization of a critically ill child must be weighted against the estimated mortality of the patient with conventional therapy alone. a predictive mortality of greater than % despite maximal medical management is the criterion most institutions use to select patients for ecmo. ecmo is indicated when a reversible disease process is present, tissue oxygenation requirements are not being met, and ventilator treatment is causing more harm than good. all ecmo centers must develop their own criteria and continually evaluate their patient selection based on ongoing outcomes data. a discussion of generally accepted selection criteria for using ecmo follows. reversible disease process: the underlying principle of ecmo relies on the premise that the patient has a reversible disease process that can be corrected with either therapy or "rest" within a relatively short period of time. exposure to high pressure mechanical ventilation with high concentrations of oxygen will frequently lead to the development of bronchopulmonary dysplasia (bpd) . bpd can result from as little as days of high-level ventilatory support. the pulmonary dysfunction following barotrauma and oxygen toxicity from mechanical ventilation can take weeks to months to resolve. therefore, patients who have received aggressive ventilation for greater than - days are not considered ecmo candidates due to the high probability of established, irreversible lung injury. gestational age: the gestational age should be at least weeks. signifi cant morbidity and mortality related to intracranial hemorrhage (ich) is associated with infants less than weeks gestational age. in preterm infants, ependymal cells within the brain are not fully developed, thus making them susceptible to hemorrhage. in addition, the systemic heparinization necessary to maintain a thrombus-free ecmo circuit also increases the risk of hemorrhagic complications ( fig. . ). birth weight: technical consideration and limitation of cannula size restrict ecmo candidates to a birth weight of , g. the smallest single lumen ecmo cannula is french (fr), and fl ow through the tube is related to the radius of the tube by a power of . babies that weigh less than kg provide technical challenges in performing cannulation and in maintaining adequate fl ow through small catheters. bleeding complications: babies with ongoing, uncontrollable bleeding or an uncorrectable bleeding diathesis pose a relative contraindication to ecmo. coagulopathy should be corrected before initiation of ecmo as the circuit requires continuous systemic heparinization. intracranial hemorrhage: patients who pose a high risk for ich are those with previous history of seizures, intracranial bleed, cerebral infarction, prematurity, coagulopathy, ischemic central nervous system injury, or sepsis. consideration of these patients for ecmo should be individualized. in general, candidates for ecmo should not have an ich. a preexisting ich may be exacerbated by the use of heparin and the unavoidable alterations in cerebral blood fl ow while on ecmo support. patients with small intraventricular (grade i or ii) or intraparenchymal hemorrhages can be successfully treated on ecmo by maintaining a lower than optimal activated clotting time (act) between and s. these patients should be closely observed for extension of intracranial bleeding with frequent neurologic exams and daily cranial ultrasonography. coexisting anomalies: the patient should have no congenital anomalies that are incompatible with life. however, many lethal pulmonary conditions such as congenital alveolar proteinosis, alveolar capillary dysplasia, and overwhelming pulmonary hypoplasia may present as reversible diseases. every effort should be made to establish a clear diagnosis before the initiation of ecmo as it is not intended to delay an inevitable death. other treatable conditions, such as total anomalous venous line pulmonary venous return and transposition of the great vessels, may initially manifest with respiratory failure but should be diagnosed with preoperative echocardiography. failure of medical management/risk assessment: ecmo candidates are expected to have a reversible cardiopulmonary disease process with a predictive mortality of greater than % despite maximal medical management. the pharmacologic agents that comprise part of the medical management include vasoconstrictive, inotropic and chronotropic agents, sedatives, and analgesics. ventilatory management usually begins with conventional support but may also include the administration of surfactant, inhaled nitric oxide, inverse inspiratory-expiratory (i/e) ratios, or high-frequency oscillation. because of the invasive nature of ecmo and the potential life-threatening complications, investigators have worked to develop an objective set of criteria to predict which infants and children have % mortality without ecmo. pulmonary insuffi ciency with associated hypoxia, hypercarbia, and acidosis is not an indication for ecmo unless tissue oxygen requirements are not being met, as evidenced by progressive metabolic acidosis, decreased mixed-venous oxygen saturation (svo ), and early evidence of multiple organ failure. the two most commonly used measurements for respiratory failure are the alveolar-arterial oxygen gradient (aado ) and the oxygenation index (oi), which are calculated as follows: aado = (p atm − ) (fio ) -[(paco )/ . ] -pao where p atm is the atmospheric pressure and fio is the inspired concentration of oxygen. where map is the mean airway pressure. although institutional criteria for ecmo vary, it is generally accepted that for neonates with an aado greater than mmhg for more than h, an aado greater than for h, or an oi greater than establishes both relatively sensitive and specifi c predictors of mortality. other criteria used by many institutions include a preductal pao less than - mmhg for - h or a ph of less than . for at least h with intractable hypotension. these are sustained values measured over a period of time and are not accurate individual predictors of mortality. older infants and children do not have such welldefi ned criteria for high mortality risk. the combination of a ventilation index respiratory ´ rate paco ´ peak inspiratory pressure , greater than and an oi greater than correlates with a - % mortality risk. a mortality of - % is associated with an aado greater than mmhg and a peak inspiratory pressure (pip) of cm h o. indications for support in patients with cardiac pathology are based on clinical signs of decreased peripheral perfusion, including hypotension, despite the administration of fl uid resuscitation and inotropes, oliguria (urine output < . ml/kg/h), an elevated arterial lactate, and a decreased svo . special mention should be made of infants with cdh who develop respiratory failure. before ecmo is initiated in an infant with cdh, the infant must fi rst demonstrate some evidence of adequate lung parenchyma. this includes maintaining a preductal oxygen saturation ≥ % for a sustained period of at least h and at least one recorded paco of less than mmhg. the goal of ecmo support is to provide oxygen delivery. many different cannula confi gurations are possible, but the three most commonly used clinically include venoarterial (va), venovenous (vv), and double-lumen venovenous (dlvv). veno-venous (vv), including single cannula, dual-lumen vv (dlvv): dlvv is used in neonates, infants, and children less than kg due to limitations of fl ow based on cannula size. the catheter is inserted into the rij, with the tip in the ra. vv ecmo bypass is established by draining the ra via the rij, with reinfusion into a femoral vein. the advantages of vv and dlvv over va ecmo include avoidance of arterial cannulation and permanent ligation of the carotid artery, maintaining pulsatile fl ow to the patient, continued blood fl ow to the lungs, and avoiding arterial emboli. a major limitation of dlvv ecmo is that there is mixing of unsaturated and saturated blood in the ra, because blood is both withdrawn and returned to the right atrium (ra). in addition, a fraction of the reinfused, oxygenated blood reenters the pump, called recirculation. recirculation artifi cially raises the svo measurement on the pump and may limit oxygen delivery at higher fl ow rates. veno-arterial (va): va ecmo offers the ability to replace both cardiac and pulmonary function. venous blood is drained from the ra through the right internal jugular vein (rij) and oxygenated blood is returned via the right common carotid artery (rcca) to the ascending aorta. there are many potential disadvantages associated with va ecmo. a major artery must be cannulated and therefore sacrifi ced. the risk of gas and particulate emboli being introduced into the systemic circulation is substantial. a decrease in the preload and an increase in the afterload may reduce cardiac output, resulting in nonpulsatile fl ow. pulmonary perfusion is reduced and the coronary arteries are largely perfused by hypoxic left ventricular blood. transthoracic cannulation is the preferred mechanism of support for cardiac surgery patients who are unable to wean off bypass postcardiotomy or in cases of cardiac arrest in the immediate to early postoperative period. the venous cannula is placed directly into the right atrial appendage and the arterial cannula in the ascending aorta. the chief disadvantages to open-chest cannulation include signifi cant risk of hemorrhage and infection (mediastinitis). patients with left heart or bi-ventricular failure are at risk of left ventricular distention. left heart decompression is needed to reduce pulmonary edema, prevent pulmonary hemorrhage, and reduce ventricular distention that may aid in recovery of function. this can be avoided with a surgically created atrial septostomy or a cannula placed directly in the left atrium via open chest cannulation; patients with a preexisting atrial septal or ventricular septal defect (asd or vsd) do not need further surgical intervention. at our institution, all patients with cardiac failure receive prophylactic atrial septostomy to prevent left-sided dilation and potential worsening cardiac function. with proper monitoring, cannulation can be performed in the neonatal or pediatric intensive care units under adequate sedation and intravenous anesthesia. the child is positioned supine with the head at the foot of the bed. the head is turned to the left and the neck is hyperextended over a shoulder roll. after local anesthesia is administered over the incision site, a transverse cervical incision is made along the anterior border of the sternocleidomastoid muscle, one fi ngerbreadth above the right clavicle. the platysma muscle is divided, the sternocleidomastoid muscle is retracted laterally, and dissection is carried down to the carotid sheath. the sheath is opened and the internal jugular vein, common carotid artery, and vagus nerve are identifi ed. the vein is dissected fi rst and isolated with vessel loops. the common carotid lies medial and posterior, contains no branches, and is mobilized in a similar fashion. the vagus nerve should be identifi ed only to protect it from injury. once the vessels have been isolated, the patient is given a bolus of u/kg of heparin sulfate, which is allowed to circulate for - min. an act level should be drawn and should be greater than s. for va bypass, the arterial cannula is placed fi rst. the carotid artery is ligated distally and once proximal control is obtained with a vessel loop a transverse arteriotomy is made near the distal ligature. stay sutures can be placed in the artery to retract and to help prevent intimal dissection. the saline-fi lled cannula is inserted to its premeasured position (tip at the junction of the brachiocephalic artery and the aorta) and secured in the vessel with - silk ligatures. additionally, a small piece of vessel loop may be placed under the ligature on the anterior aspect of the carotid to protect the vessel from injury during decannulation. the patient must be paralyzed with succinylcholine before venous cannulation to inhibit spontaneous respiration and prevent air emboli. the jugular vein is then ligated and a venotomy is made close to the ligature. the saline-fi lled venous catheter is passed to a measured level of the ra and secured as described above. any bubbles are aspirated from the cannulas, which are then connected to the preprimed ecmo circuit and bypass is initiated. the cannulae should then be secured to the patient's skin above the wound and the skin closed in layers to ensure meticulous hemostasis. for vv and dlvv bypass, the procedure is exactly as described above, including dissection of the artery with the placement of a vessel loop to facilitate conversion to va ecmo should the need arise. the venous catheter tip should be positioned in the mid-right atrium with the arterial portion of the dlvv catheter oriented medially to direct the fl ow of oxygenated blood toward the tricuspid valve. the cannula position is confi rmed by chest radiography and transthoracic echocardiogram and readjusted as needed. venous blood is drained from the infant or child by gravity into a small reservoir or bladder. an in-line oxymetric probe is located between the venous return cannula and the bladder to continuously monitor the svo saturation. the bladder is a -to -ml reservoir that acts as a safety valve. in the event venous drainage does not keep up with the arterial fl ow from the pump, the bladder volume will be depleted, the pump will be automatically shut off, and an alarm will be sounded. this serves to limit the potential for injury to the ra, rij, or cavitation of air and high negative pressures within the circuit. hypovolemia is one of the common causes of decreased venous infl ow into the circuit, but kinking with occlusion of the venous line should be suspected fi rst. in addition, the height of the patient's bed can be raised to improve venous drainage by gravity. a displacement roller pump pushes blood through the membrane oxygenator. the roller pumps are designed with microprocessors that allow calculation of the blood fl ow based on roller-head speed and tubing diameter of the circuit. in other words, the speed at which the pump is set determines what proportion of the patient's cardiac output will be diverted into the circuit and is adjusted according to how much support the patient requires. the pumps are connected to continuous pressure monitoring throughout the circuit and are servoregulated if pressures within the circuit exceed preset parameters. another safety device, the bubble detector, is interposed between the pump and the membrane oxygenator and will stop fl ow if air is detected within the circuit. the blood enters the membrane lung, after exiting the pump. the oxygenator consists of a long, two-compartment chamber composed of a spiral-wound silicone membrane and a polycarbonate core. this provides a large surface area across which blood and gas come into close contact, with blood fl owing in one direction and gas fl owing in the opposite direction. oxygen diffuses through the membrane into the blood circuit and carbon dioxide and water vapor diffuse from the blood into the sweep gas. the size (surface area) of the oxygenator chosen is based on the patient's weight and size. the blood emerges from the upper end of the oxygenator and passes through the countercurrent heat exchanger returning to the body at physiologic temperature into the ra (via dlvv cannulation) or the aortic arch via the rcca. prime management: the tubing of the ecmo circuit is initially circulated with carbon dioxide gas. this is followed by the addition of crystalloid and % albumin solution. the albumin coats the tubing to decrease its reactivity to circulating blood. the carbon dioxide gas dissolves into the fl uid. approximately two units of packed red blood cells are required for initial priming of the pump, which displaces the crystalloid and colloid in the circuit. the initial ph, oxygen content, and carbon dioxide content of the circuit are then measured and adjusted to physiologic parameters. if the prime blood is acidotic, this may exacerbate the infant's condition; or if the primed circuit has low carbon dioxide content, this may cause metabolic problems for the neonate. additionally, a heat exchanger warms the prime to normal body temperature. in sum, the primed circuit must be physiologically compatible with life prior to initiating ecmo to maximize support and prevent initial worsening of the child's condition. pump management: the goal of ecmo is to maintain adequate pump fl ow, which will result in good oxygen delivery to the tissues and organs. oxygen delivery to the infant is dependent on the speed or rotations per minute (rpm) of the roller pump. full bypass support is considered cc/kg/min on vv ecmo and cc/kg/min on va ecmo. to increase a patient's oxygen level on ecmo, one can either increase the fl ow rate (∼cardiac output) or increase oxygen carrying capacity with transfusion of prbc to maintain a hemoglobin level of g/dl (∼oxygen content). with va ecmo, adequate perfusion and oxygen delivery can be monitored by the ph and po of a mixed venous blood sample (pre-oxygenator blood sample). the fl ow of the roller pump should be adjusted to maintain a mixed venous po of - mmhg and svo of - %. with vv ecmo, the mixed venous sample may not be a reliable indicator of perfusion as recirculation may produce a falsely elevated po . therefore, other indicators of poor perfusion should be followed, such as persistent metabolic acidosis, oliguria, seizures, elevated liver function tests, and hypotension. if oxygen delivery is found to be inadequate, then the rpm of the pump may need to be increased to improve perfusion. roller pumps roll against the tubing to propel the blood towards the oxygenator. this area of contact is at risk of tubing rupture over time. to reduce the risk of rupture, the raceway is advanced every - days after temporarily stopping the pump flow. tubing rupture is a rare event because of modern materials such as supertygon (norton performance plastics corp., akron, oh), a chemically altered polyvinyl chloride (pvc). the tubing should be inspected daily and all connections secured properly and replaced if defective. when a raceway rupture does occur, the pump must be turned off immediately, the patient must be ventilated and perfused with conventional methods (increased ventilator pressures and fio ), and cpr performed if necessary. the raceway tubing is then replaced or the entire circuit can be changed. oxygenator management: the silicone membrane (envelope) oxygenator (avecor, inc., minneapolis, mn) is critical to the success of ecmo and long-term bypass. the mechanism of gas exchange occurs when blood in the tubing enters a manifold region and is distributed around the envelope of a silicone membrane lung. oxygen, which is mixed with a small amount of carbon dioxide to prevent hypocapnea, fl ows through the inside of the membrane envelope in a countercurrent direction to the fl ow of blood. oxygen diffuses across the silicone membrane into the blood as carbon dioxide is eliminated. the oxygenated blood drains into a manifold and is returned to the infant via a heat exchanger. thrombus may form in the oxygenator over time. as the thrombus extends, the membrane surface area decreases, resulting in decreased oxygenation, increased carbon dioxide retention, and increased resistance to blood fl ow. signs of clot formation can be detected by direct visualization of the top or bottom of the membrane, but the extent of the clot cannot be determined. another sign of clot formation within the oxygenator is progressive consumption of clotting factors such as platelets and fi brinogen. the gaseous portion of the oxygenator may also develop obstructions, which may lead to air emboli. long-term use may wear out the silicone membrane resulting in blood and water in the gas phase causing water condensation. therefore, the oxygenator should be replaced when the postoxygenator po decreases to < mmhg or pre-oxygenator circuit pressures increase to over mmhg at fl ow rates required to support the patient. in addition, a larger oxygenator may also be required if the gas and blood fl ow rating of the old oxygenator are exceeded in order to maintain adequate perfusion. volume management: while on ecmo, maintenance fl uids for a term newborn under a radiant warmer are estimated at cc/kg/day. water loss through the oxygenator may approach cc/m /h. for a kg baby, this would be about cc/kg/day. fluid losses from urine, stool, chest tubes, nasogastric tubes, ostomies, mechanical ventilation, radiant fl uid loss, and blood draws should be carefully recorded and repleted. fluid management may become diffi cult in the ecmo baby as fl uid extravasates into the soft tissues during the early ecmo course. therefore, meticulous recordings of the net fl uid balance should be maintained on ecmo. classically, the weight increases in the fi rst - days as the patient becomes increasingly edematous. starting the third day on ecmo, diuresis of the excess edema fl uid begins, and can be facilitated with the use of furosemide. this diuretic phase is often the harbinger of recovery. in the event of renal failure on ecmo, hemofi ltration or hemodialysis can be added to the ecmo circuit for removal of excess fl uid and electrolyte correction. respiratory management: once the desired fl ow is attained, the ventilator should be promptly weaned to avoid further oxygen toxicity and barotrauma. such "rest settings" have been studied and debated. at our institution, we decrease the fio to . , peep to cm h o, pip to - cm h o, a rate of breaths/min, and inspiratory time of . s if the infant's arterial and venous oxygenation are adequate. if the baby remains hypoxic despite maximal pump fl ow, then higher ventilator settings may be temporarily required. alternatively, hypoxic neonates on vv ecmo may need to be converted to va ecmo for full cardio-respiratory support. on occasion, the chest x-ray will worsen in the fi rst h independent of ventilator settings and will improve after diuresis. as the patient improves on ecmo and the pump fl ow is weaned, ventilator settings are then modestly increased to support the baby off ecmo. in addition, during the course of ecmo, pulmonary toilet is essential to respiratory improvement and includes gentle chest percussion and postural drainage. special attention should be paid to the ecmo catheters and to keep the head and body aligned. endotracheal suctioning is also recommended every h and as needed based on the amount of pulmonary secretions present. medical management: after the initiation of ecmo, vasoactive medications should be quickly weaned down if the blood pressure remains stable. low-dose dopamine ( mcg/kg/min) can be administered for renal protection, although its use is controversial. in the event of seizures, phenobarbital is usually given and maintained to prevent further seizures. in addition, gastrointestinal prophylaxis with an h -blocker, such as ranitidine, is instituted. fentanyl and midazolam is usually administered for mild sedation; however, the use of paralytics should be avoided as muscle activity is not only important for fl uid mobilization but also to monitor neurologic activity. infectious prophylaxis is provided by the use of ampicillin and gentamicin, which covers most common bacterial infections. with the use of gentamicin, attention should be directed to renal function. for this reason, cefotaxime may be used for gram-negative coverage instead of gentamicin. because of the cannula and manipulation of the circuit at stopcocks, the risk of infection is a constant concern; therefore, strict observance to aseptic technique when handling the ecmo circuit should be maintained. daily routine blood, urine, and tracheal cultures should be obtained to monitor for infection. caloric intake on ecmo should be maximized using standard hyperalimentation. for a newborn, total parenteral nutrition (tpn) should be started at kcal/ kg/day. normally, this should be supplied as % carbohydrates ( . gm/kg/day) and % fat ( . gm/kg/ day). intralipid infusions may be used as a fat source, although there is some controversy with its use in the setting of severe lung disease. as a result, the percentage of fat in the hyperalimentation may be lowered. amino acids may be added but must be considered in the setting of poor renal function and increasing bun levels. with normal renal function, approximately . gm protein/kg/day should be provided in the tpn mixture. electrolytes should be closely monitored with potassium, calcium, and magnesium repleted as necessary. while on ecmo, the patient's hemoglobin is maintained at gm/dl to maximize the oxygen carrying capacity of the blood. platelet destruction during ecmo is anticipated and is secondary to the fl ow through the oxygenator. in order to reduce the risk of bleeding during ecmo, the platelet count should be kept above , /mm. we recommend using "hyperspun" platelets in neonates to avoid the excess administration of fl uid, and thus prevent further problems with volume overload and edema. heparin is initially administered as a bolus ( - mg/kg) followed by constant heparin infusion ( - mg/kg/h) to maintain a thrombus-free circuit. the level of anticoagulation is monitored hourly by the activated clotting time (act). the heparin infusion is adjusted to maintain an act of - s. after decannulating, the heparin infusion is stopped and not reversed with protamine sulfate. operative procedures on ecmo: surgical procedures, such as cdh repair, may be safely performed while the child remains on bypass. however, care must be taken to obtain meticulous hemostasis to avoid hemorrhagic complications. before any invasive procedure, platelets should be transfused to a level greater than , /mm and the act level dropped to - s. the fi brinolysis inhibitor aminocaproic acid is administered as a mg/kg bolus min prior to incision and maintained at a continuous drip at ml/kg/h for h postoperatively. weaning and decannulation: as the patient's underlying process improves, less blood fl ow is required to pass through the ecmo circuit in order to maintain adequate tissue oxygenation. the fl ow rate may be weaned slowly ( - ml/h) as long as the patient maintains oxygen saturations with evidence of adequate perfusion. the most important guide to weaning on va ecmo is the svo and for vv ecmo, the sao . when fl ow levels have decreased until they approximate % of the patient's cardiac output (∼ - cc/kg/min), the patient is usually ready for decannulation. as fl ow levels are decreased, the heparin drip should be increased for an act of - s to prevent thrombotic complications. ventilator settings can be increased moderately if saturations drop during weaning, but should not revert to pre-ecmo settings. if the child continues to tolerate low fl ow, all medications and fl uids should be switched to vascular access on the patient side and the cannulas can be clamped and fl ushed with heparanized saline ( u/ml). flow is maintained within the circuit with the bridge open as the possibility that the child may not tolerate clamping and may need to be placed back on bypass remains. once the cannulas are clamped, the child is observed for - h. if he or she remains hemodynamically stable, with adequate saturations and does not become acidotic during this period, decannulation can safely be accomplished. decannulation is performed in the icu using a near-identical manner as cannulation. this should be done under sterile conditions in the trendelenburg position using a muscle relaxant to prevent air aspiration into the vein. once the cannula is withdrawn, the vessel is ligated, the wound irrigated, and closed over a small drain. complications on ecmo can be divided into technical, mechanical, or pump-related and patient-related. the most common technical complications include vessel injury or dissection during cannulation, cannula malposition and kinking, accidental decannulation, and limb ischemia from occlusion of distal fl ow. most technical complications can be avoided with proper surgical technique and securing of the cannulas. limb ischemia can be avoided with the placement of a distal perfusion catheter when signs of ischemia develop (loss of pulse, cool, mottled, or swollen extremity). mechanical complications include oxygenator failure, tubing rupture in the raceway (both described above), clot formation within the circuit tubing, and the introduction of air into the circuit. if clot is detected on the venous or pre-oxygenator side of the circuit, it can often be observed or segments of tubing can be selectively replaced. clots on the arterial or postoxygenator side of the circuit are cause for concern as they can break off and cause emboli with pulmonary and neurologic complications. when a clot is detected on the arterial side, the entire circuit should be exchanged for a fresh preprimed circuit. the introduction of air into the circuit is possible during the initial cannulation as well as through several connectors, tubing stop-cocks, and the membrane oxygenator. prevention of air embolism is vital; when setting up the circuit, all air must be removed and all connections made tight and thoroughly inspected and the circuit must be continuously monitored. if air is detected on the venous side, it can often be aspirated from one of the ports without coming off bypass. air on the arterial side is an emergency and requires the patient to be taken off bypass immediately until it can be safely aspirated. in the event that an air embolism reaches the patient, ecmo should be stopped, the patient placed in trendelenburg position, and an attempt should be made to aspirate any air out of the arterial cannula. if air enters the coronary circulation, inotropic support may be necessary. the most common patient complications are bleeding (cannula site . - . %, surgical site . - . %, intracranial . - . %, gi . - . %, tracheal, urinary) and coagulation disorders (hemolysis %, dic . %). contact of blood with the foreign surface of the circuit activates the coagulation cascade. platelets are consumed by the circuit and their function is also affected. constant monitoring for signs of bleeding include observing for tachycardia, hypotension, a decreased hematocrit, or inadequate venous return are signs of hemorrhage. treatment includes replenishing lost blood products, including platelets and coagulation factors, if necessary. patients on ecmo may also have hemodynamic compromise, including hypotension or hypertension. according to the elso registry, . % of neonates and % of pediatric patients treated with ecmo for respiratory failure required the use of inotropes while on bypass. hypotension can be from volume depletion (including blood loss) as well as decreased myocardial function from hypoxia prior to the initiation of ecmo support. inotropes are often easily weaned when hypoxia is reversed, but euvolemia and adequate hct should be maintained. hypertension requiring the use of vasodilators was reported in . % of neonates and . % of pediatric patients. the patient should be assessed for reversible causes of hypertension such as pain, hypercarbia, and hypoxia. hypertension should be aggressively treated due to the increased risk of intracerebral hemorrhage in ecmo patients. neurologic complications including intracerebral hemorrhage (ich), infarct and stroke, and seizures can occur with an overall incidence of - %. seizures are widely reported among ecmo neonates, ranging from % to %. however, only % had a continued diagnosis of epilepsy at years of age. seizures in the neonatal ecmo population are associated with neurologic disease and poorer outcomes, including epilepsy and cerebral palsy. the incidence of ich and infarct is recorded at % in neonates and % in pediatric patients on ecmo. as stated earlier, the risk is increased in low birth weight infants and premature infants < weeks gestation. patients with small interventricular (grade i or ii) or intraparenchymal hemorrhages can be successfully treated on ecmo by maintaining a lower than optimal activated clotting time (act) between and s. these patients should be closely observed for extension of intracranial bleeding with frequent neurologic exams and daily cranial ultrasonography. any progression or change in neurologic status requires cessation of anticoagulation and thus removal from ecmo support. oliguria and a slight rise in creatinine are common in ecmo patients and are often seen during the fi rst - h. the capillary leak seen after placing a child on ecmo may cause decreased renal perfusion, or it may be due to the nonpulsatile nature of blood fl ow seen in va ecmo. once the patient is adequately volume resuscitated, furosemide can be used to improve urine output. the incidence of acute renal failure was % in neonates and % in pediatric patients on ecmo for respiratory support, with - % requiring hemofi ltration or dialysis. continuous hemofi ltration can be easily added in-line to the ecmo circuit and provides assistance with fl uid balance, hyperkalemia, and azotemia, which is often not needed after ecmo support is withdrawn. hemofi ltration removes plasma water and dissolved solutes while retaining proteins and cellular components of the intravascular space. the incidence of acquiring a nosocomial infection on ecmo has been reported at - %. associated risk factors include the duration of the ecmo run, the length of hospitalization, type of cannulation (open chest vs neck), and surgical procedures performed before or during ecmo. fungal infections and sepsis carry a signifi cantly higher morbidity and mortality rates. in addition, because of the large volume of blood products transfused into ecmo patients, the risk of developing a bloodborne infectious disease is significant. one study states that approximately % of children who were treated with ecmo as neonates were seropositive for antibodies to the hepatitis c virus. there has been a decline in the use of ecmo for neonatal respiratory failure secondary to improved medical management (permissive hypercapnea and spontaneous ventilation, ino, surfactant, and hfov). inhaled nitric oxide (ino), a selective pulmonary vasodilator, improves oxygenation and has signifi cantly contributed to the recent decrease in the need for extracorporeal membrane oxygenation (ecmo) in neonates with respiratory failure. in addition to ino, high-frequency ventilation, the adjunct use of surfactant therapy, and improved cardiovascular support have recently been shown to decrease the need for ecmo in this patient population. according to a -year retrospective review of the elso registry data published in , the use of surfactant, high-frequency ventilation, and inhaled nitric oxide in patients with respiratory failure who required ecmo increased from % in to %, %, and %, respectively, in . the proportion of neonates with cdh requiring ecmo increased from % to %, while the proportion with respiratory distress syndrome decreased from % to %. in contrast, the number of cardiac cases had steadily increased over years with a peak in ; however, there was a notable decline in and . this could be due to decreased use secondary to the poor overall survival reported, increased organ procurement and transplantation, or use of other methods of support, including the berlin heart excor (berlin heart ® , berlin heart ag, berlin, germany), lvad, and bivad. in a recent study at our institution, we reviewed all transplant-related use of ecmo in patients who were placed on extracorporeal life support as a bridge to cardiac transplantation. the aggregate survival of these patients was % ( / ) but those who were successfully bridged to a cardiac transplant (i.e., survived on ecmo until transplanted) had % ( / ) survival. overall survival to discharge for neonates and pediatric patients treated with ecmo is dependent again on initial diagnosis. higher survival rates are seen in neonates with respiratory diseases ( %) than cardiac diseases ( %). within the neonatal population, newborns with mas that require ecmo have the highest survival rate at %, whereas survival for infants with cdh is %. the pediatric population of ecmo patients represents a diverse group with regard to patient age as well as diagnosis. over double the number of cardiac cases have been reported in the pediatric population compared to the respiratory cases ( , vs , at the end of ). higher complication rates exist with the pediatric patients, refl ecting the more complicated disease states as well as the longer duration of bypass required for reversal of the respiratory or cardiac failure. common long-term problems in ecmo-treated infants and children include feeding and growth sequelae, respiratory complications, and neurodevelopmental delays. these children are at increased risk for complications both as a consequence of ecmo itself and from antecedent hypoxia, acidosis, and reperfusion injury. approximately, one-third of infants treated with ecmo have feeding problems. the possible causes are numerous and include tachypnea, generalized central nervous system depression, poor hunger drive, postsurgical neck soreness (possibly from compression of the vagus nerve), and poor oral-motor coordination. cdh babies have a higher incidence of feeding diffi culties as compared with infants with mas secondary to foregut dysmotility, which leads to signifi cant gerd and delayed gastric emptying. respiratory compromise and chronic lung disease compound the problem. normal growth is most commonly reported in ecmo-treated patients; yet these children are more likely to experience problems with growth than agematched normal controls. head circumference below the fi fth percentile occurs in % of ecmo-treated children. growth problems are most commonly associated with ecmo children who have suffered from cdh or residual lung disease. neonatal ecmo survivors have a relatively high incidence of respiratory abnormalities initially with % requiring supplemental oxygen at days of age and % having at least one episode of pneumonia by the age of years as compared with controls ( %). these children with pneumonia are more likely to require hospitalization, and pneumonia occurs at a younger age, with over half diagnosed in the fi rst year of life. cdh infants, in particular, have been found to have severe lung disease after ecmo and may require supplemental oxygen therapy at home. probably the most serious post-ecmo morbidity is neuromotor handicap. most studies show approximately % ( - %) ecmo survivors exhibit some type of handicap, with an - % incidence of moderate-to-severe cognitive delay. auditory defects are noted in over one-fourth of ecmo neonates at discharge, with sensorineural hearing loss in ∼ %, speech and language delay in ∼ % with roughly - % requiring speech and language therapy. healthcareassociated infection in pediatric patients on extracorporeal life support: the role of multidisciplinary surveillance international registry report of the extracorporeal life support organization extracorporeal membrane oxygenation neurodevelopmental outcome of infants supported with extracorporeal membrane oxygenation after cardiac surgery ecmo in the newborn pediatric surgery how low can you go? effectiveness and safety of extracorporeal membrane oxygenation in lowbirth-weight neonates key: cord- -jby btv authors: rilinger, jonathan; zotzmann, viviane; bemtgen, xavier; schumacher, carin; biever, paul m.; duerschmied, daniel; kaier, klaus; stachon, peter; von zur mühlen, constantin; zehender, manfred; bode, christoph; staudacher, dawid l.; wengenmayer, tobias title: prone positioning in severe ards requiring extracorporeal membrane oxygenation date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: jby btv background: prone positioning (pp) has shown to improve survival in patients with severe acute respiratory distress syndrome (ards). to this point, it is unclear if pp is also beneficial for ards patients treated with veno-venous extracorporeal membrane oxygenation (vv ecmo) support. methods: we report retrospective data of a single-centre registry of patients with severe ards requiring vv ecmo support between october and may . patients were allocated to the pp group if pp was performed during vv ecmo treatment or the supine positioning group. vv ecmo weaning success and hospital survival were analysed before and after propensity score matching. results: a total of patients could be analysed, and patients ( . %) received pp. there were no significant differences in vv ecmo weaning rate ( . % vs. . %, p = . ) and hospital survival ( . % vs. . %, p = . ) between the prone and supine groups, respectively. the analysis of propensity score matched pairs also showed no difference in hospital survival ( . % vs. . %, p = . ) or vv ecmo weaning rate ( . % vs. . %, p = . ). hospital survival was superior in the subgroup of patients treated with early pp (cutoff < h via youden’s index) as compared to late or no pp ( . % vs. . %, p = . ). conclusion: in this propensity score matched cohort of severe ards patients requiring vv ecmo support, prone positioning at any time was not associated with improved weaning or survival. however, early initiation of prone positioning was linked to a significant reduction of hospital mortality. in case of severe acute respiratory distress syndrome (ards), veno-venous extracorporeal membrane oxygenation (vv ecmo) support may be considered when lung-protective mechanical ventilation is not able to prevent hypoxia or hypercapnia [ ] [ ] [ ] . nevertheless, mortality of severe ards remains high-even with ecmo support. the eolia trial for instance showed a mortality rate of % in patients treated with ecmo compared to % in patients without ecmo support in very severe ards [ ] . moreover, several studies showed that prone positioning (pp) is able to improve survival in these critically ill patients [ , ] . pp provides various positive effects on oxygenation and lung compliance [ , ] . furthermore, pp can reduce ventilator-induced lung injury [ ] and is associated with less days on mechanical ventilation (mv) and shorter length of intensive care unit (icu) stay [ ] . hence, pp might be beneficial for patients receiving ecmo support. it has been demonstrated that pp can be performed safely [ ] [ ] [ ] [ ] [ ] during ecmo support and improves oxygenation and lung compliance [ ] . so far, there is little evidence about the outcome of these patients. we performed a retrospective analysis of ards patients treated with pp during ecmo support at our centre. we report retrospective data of a single-centre registry of patients with severe ards treated with vv ecmo. all patients treated at the interdisciplinary medical intensive care unit at the medical centre, university of freiburg, germany, between october and may were registered. patient identity data derived from the registry were blinded, and the study plan was approved by the local ethics committee (ek-freiburg / ). all patients suffered from severe ards. vv ecmo support was initiated in cases of severe hypoxic respiratory failure or co retention despite of mechanical ventilation as suggested by the elso guidelines. patients receiving pp during ecmo support were allocated to the prone group, whereas the remaining patients formed the supine group. pp before initiation of ecmo support did not influence the allocation of patients in one or the other group. primary endpoints were successful ecmo weaning, and icu and hospital survival. successful ecmo weaning was defined as being free from ecmo and alive for at least h after decannulation. unsuccessful weaning was defined as the inability to explant the ecmo device because of persistent respiratory failure or death during ecmo support and the need for recannulation within h. moreover, ventilator settings of the first days after ecmo initiation were analysed. to compare the patients' disease severity, the resp [ ] , sofa [ ] , and apache ii scores [ ] as well as the horowitz index (pao /fio ) were analysed. our institution features a / ecmo centre localised within a tertiary hospital with a -bed medical intensive care unit. cannulations in our ecmo centre are performed by two experienced intensivists and a perfusionist in seldinger's technique without primary surgical cut down. all member of the ecmo team can be gathered within min. typical numbers for veno-arterial and veno-venous cannulations are and per year, respectively. there is a h/ days outreach team. for this research, only in-house cases were considered. as ecmo system, either scpc (sorin centrifugal pump console, livanova, london, uk) or cardiohelp (maquet getlinge group, rastatt, germany) was used. cannulation was predominantly performed with dual-lumen cannula (avalon, maquet, rastatt, germany). for patients without life-threatening bleeding, anticoagulation was provided by intravenous unfractionated heparin aiming at a partial thromboplastin time . times upper normal limit. the management of vasopressors and fluid therapy was driven by clinical judgement of the ecmo experienced intensivist in charge and has been reported earlier [ ] . treatment algorithms and standard operating procedures were subject to optimizations during the observational period, reflecting current state-of-the-art recommendations and scientific knowledge. controlled mv mode used at our institution mostly was biphasic positive airway pressure (bipap). in few patients, airway pressure release ventilation (aprv) was used, when considered beneficial. vv ecmo support was implemented in case of severe but potentially reversible respiratory failure, when lung-protective mv resulted in hypoxemia or hypercapnia. lung-protective mv was defined as positive end expiratory pressure (peep) ≤ cmh o, plateau pressure ≤ cmh o, driving pressure ≤ cmh o, and fio ≤ %. cannulation was performed predominately jugulary using a duallumen cannula. after initiation of the vv ecmo support, invasivity of mv was reduced and ecmo flow was adjusted aiming for a peripheral oxygen saturation of - % and partial pressure arterial oxygen of approximately mmhg, respectively. typical ventilator settings were as follows: peep cmh o, plateau pressure cmh o, fio %, and respiratory rate /min. indications and performance of prone positioning during ecmo support ards treatment was carried out according to the currently valid guidelines [ ] . the decision on whether to perform pp in the individual case lays with the treating medical team's judgement. prone positioning was done face down. sedation for pp patients at our institution was titrated to preserve spontaneous breathing if possible. neuromuscular blockade was not given on a routine basis for executing pp. however, in individual cases, especially in cases of strong respiratory drive and concerns about a self-inflicted lung injury [ ] , neuromuscular blocking agents were used. summary results for categorical variables are presented as frequency and percentage. results for numeric variables are presented as median with interquartile range (iqr). fisher's exact test and pearson's chisquared test were used for analysing nominal variables. in dependence of normal distribution, student's t test or mann-whitney u test was performed for continuous variables. multivariate regression analysis was performed for univariate (dependent) predictors of hospital survival. results are given as odds ratio [(or), % confidence interval (ci)], and a p value of ≤ . was considered statistically significant. roc analysis and youden's index (youden's index = sensitivity + specificity − ) were used for reaching the optimal cutoff of survival-associated factors with highest discrimination of sensitivity and specificity. propensity score matching was performed using spss with a nearest neighbour matching algorithm using a calliper of . . matching was performed for age, sex, sofa score, the duration of mv before ecmo, and performance of prior pp before ecmo. cumulative incidences of -day mortality were calculated using competing risk regression (fine and gray method) with discharge alive considered a competing event [ ] . statistical calculations were performed using ibm spss statistics . (armonk, ny: ibm corp, ). a total of patients with complete medical data could be analysed (age . ( . - . ) years, % male). the collective showed a relatively high rate of comorbidities, and this was especially true for immunosuppression ( %, table ) . thirty-eight patients ( . %) received pp during ecmo therapy. no relevant complications (e.g. decannulation) occurred during the positioning procedures. patients with pp during ecmo support had a higher rate of pre-existing chronic renal failure and pneumoniainduced ards. patients in the prone group displayed a different pulmonary pathogen spectrum (more viral and fungal infections, especially pneumocystis jirovecii, table ). survival prediction scores (sofa, apache ii, and resp) did not differ between both groups. pp before ecmo initiation was performed in . % of the patients in both groups. on average, the first pp during ecmo support was performed after . ( . - . ) days on ecmo support, with . ( . - . ) pp manoeuvres performed per patient. average pp duration was . ( . - . ) h (additional file , table e ). patients with pp during ecmo support showed higher peep levels from day and higher plateau pressures from day to (additional file , figure e ). there was no difference in driving pressures as well as in tidal volumes. however, patients with pp during ecmo support showed less spontaneous breathing on day and day to . there were no differences in ecmo weaning rate ( . % vs. . %, p = . ), and icu or hospital survival ( . % vs. . %, respectively, p = . ) between the prone and the supine groups (table ) . cumulative incidences of -day in-hospital death were % and % for the prone and supine groups, respectively (p = . , fig. ). thirty-eight propensity score matched pairs ( patients) with similar baseline characteristics could be analysed (fig. , see also additional file , table e ). successful ecmo weaning rate was . % vs. . % (p = . ) in patients with and without pp during ecmo support, respectively. furthermore, there was no difference in survival between both groups ( . % vs. . %, p = . ). cumulative incidences of -day in-hospital death were % and % for the prone and supine groups, respectively (p = . , additional file , figure e ). underlying lung fibrosis, status of immunosuppression, and aspiration were associated with death, whereas proof of bacterial infections was associated with survival (table ) . moreover, a high proportion of spontaneous breathing in the first days was strongly associated with survival. in multivariate analysis, only underlying lung fibrosis (odds ratio . [ % ci . - . ]) and a high proportion of spontaneous breathing in the first days (odds ratio . [ % ci . - . ]) were independent predictors for death and survival, respectively. in patients with pp, higher age, acute renal failure, and underlying pulmonary disease were associated with death. proof of pulmonary bacterial infection and timing of the first pp after ecmo initiation were associated with survival in a univariate analysis (additional file , table e ). in a multivariate analysis, only early initiation of pp (< h) was associated with survival (odds ratio . [ % ci . - . ], fig. ). optimal cutoff value for duration from ecmo initiation to first pp was calculated using roc analysis (auc = . ) and youden's index. highest sensitivity and specificity for beneficial survival were achieved for initiation of pp in < h. next to this optimal cutoff, a clinical cutoff of day ( h) also was associated with improved survival (p = . ). patients treated with early pp during ecmo (n = ) showed a superior survival to patients treated with late pp or without pp during ecmo support ( . % vs. . %). cumulative incidences of -day in-hospital death were % for the early pp group and % for the late and no pp group, respectively (p = . , fig. ) . also, in a separate comparison of patients with late pp as well as patients without pp, early pp showed superior survival rates ( . % vs. . % and . %, p < . and p = . , respectively). patients in the early pp group were younger than patients with late or without pp during ecmo support ( . vs. . years, p = . ). the groups did not differ concerning vasoactive support or in sofa and apac he ii scores at the time of ecmo implantation. moreover, there was no difference in the sofa score between both groups in the first days (additional file , table e ). the resp score of the patients with early pp was higher ( . ( . - . ) vs. (− . - . ), p = . , additional file , table e ). the resp score without including age was ( . - . ) vs. ( - . ), p = . ). prone positioning has shown to improve survival in non-ecmo ards patients [ ] . there is sparse data on pp in ards patients with vv ecmo support. we therefore retrospectively analysed a large cohort of ecmo patients suffering from severe ards treated with or without pp at our centre. our results do not indicate an overall survival benefit for pp during ecmo support per se. however, timing of pp may be crucial when designing future studies. in comparison to previous pp studies, technical execution of pp in this analysis showed favourable characteristics. beginning of pp after ecmo initiation was earlier than in other studies ( . vs. or days, respectively) [ , ] . moreover, the average duration of each performed pp was longer ( . h) and more pp manoeuvres were performed per patient ( . ) than described before [ , , ] . this is especially important, as the survival benefit for pp in ards without ecmo support shown by guerin et al. was achieved with long pp periods ( h) [ ] . patients treated with pp in our patient collective showed increased peep and plateau pressure levels but still remained in the recommended limits of the elso guideline [ ] . as intended by the treating medical team, driving pressure was kept below cmh o, as high driving pressures are strongly associated with increased mortality [ ] . furthermore, no differences in driving pressure were found between both groups. patients with pp during ecmo showed a reduced rate of spontaneous breathing compared to patients without pp, despite the fact that neuromuscular blocking agents were not used on a routine basis during pp periods. however, it seems reasonable that pp patients might have been on deeper sedation levels than patients in the supine group. in contrast to this, the elso guidelines recommend an early reduction of sedation levels and a switch to spontaneous breathing after to h after ecmo initiation [ ] . furthermore, low proportions of spontaneous breathing episodes were associated with a higher mortality. however, this only allows hypothesis generating, since causality between a reduced rate of spontaneous breathing and increased mortality cannot be proven in this analysis and could also be an expression of higher disease severity. nevertheless, the reduced rate of spontaneous breathing in patients with pp should be considered in the discussion of benefits and disadvantages of this additional treatment. our results are in contrast to the study of guervilly et al. their retrospective study of additional pp showed an encouraging survival benefit [ ] . survival rate in the pp group was markedly higher than in the supine group ( -day survival % vs. %). in terms of age, sex, and pp manoeuvres performed per patient, the cohort of guervilly et al. and our patients did not differ. however, our patients were sicker than those of guervilly and coworkers (predicted mortality by sofa score approx. % vs. % [ ] ) and showed a much lower rate of fig. in-hospital death of ecmo patients with vs. without prone positioning during ecmo. the fine-gray model for in-hospital death (shr . , p = . , cumulative incidence of -day death % vs. %). ecmo, extracorporeal membrane oxygenation fig. propensity score matched pair patient assignment. *matching was performed for age, sex, sofa score, the duration of mv before ecmo, and performance of prior pp before ecmo. ecmo, extracorporeal membrane oxygenation; mv, mechanical ventilation; pp, prone positioning; sofa, sequential organ failure assessment prior pp before ecmo ( % vs. %). furthermore, guervilly et al. reported deep sedation and routine use of neuromuscular blocking agents during pp which is in contrast to our approach. to compare our findings with those from guervilly et al., we used the same matching parameters for propensity score matching, which did not alter our findings. timing of pp was an independent predictor of survival in our cohort. early initiation of pp after ecmo cannulation was strongly associated with improved survival. a beginning of pp in less than day (cutoff < h via youden's index) in comparison to late or no pp showed a strong survival benefit ( % vs. %). this finding is in line with the study protocol of the proseva trial [ ] , where the survival benefit for pp in non-ecmo ards patients was achieved with an early beginning of pp (initiated in average h after beginning of mechanical ventilation). this association suggests that an early beginning of pp after initiation of ecmo support could be an important factor for survival, which requires further investigation. because of the retrospective design of this study, the reasons why patients were treated with pp or not, or received early or late pp, cannot be pinned down. patients receiving early pp were younger, but they did not differ in terms of haemodynamic stability and showed no difference regarding the sofa and apache ii scores. patients of the early pp group showed a higher resp score ( . vs. ), indicating a certain difference in predicted mortality rate ( % vs. %). nevertheless, the factor age could have influenced the team's decisionmaking for or against early pp. interestingly, in the early pp group, in contrast to the whole pp group, a higher rate of spontaneous breathing within the first days was observed (not significant), which could be one factor that may improve survival rate for early pp. from a theoretical standpoint, there are many positive effects of additional pp in patients receiving ecmo support, like improving oxygenation and lung compliance as well as reducing ventilator-induced lung injury [ ] [ ] [ ] . in clinical practice, patient-safety concerns often prevent prone positioning during ecmo therapy, even though feasibility and safety have been demonstrated in several studies. in this retrospective analysis, pp at any time was not associated with improved survival per se. however, our results indicate that a very early initiation of pp therapy (within day after cannulation) could be beneficial. no complications related to pp were detected. in consideration of the retrospective design of this study, we think that a randomised controlled trial is imperatively needed for further evaluation of pp in ecmo patients. considering the pros and cons of a pp therapy, pp should not be withheld from ards patients requiring ecmo support. our data suggest that pp should be initiated very early in the clinical course. this is a retrospective observational study and therefore contains the risk of selection and reporting bias. another limitation is the small sample size of only patients with pp and patients in the matched pair analysis, respectively. moreover, this is a single-centre report and specific processes may influence the presented results. the same internal standard operating procedures applied to the entire treating physician team. however, the indication for performing pp during ecmo support was on basis of the treating ecmo physician and therefore was not standardised. despite using propensity score matching for outcome analysis, this among other factors might be remaining confounders that we did not control for. together, due to these limitations, our findings should be considered as hypothesis generating and should not prompt clinical decision-making. this retrospective analysis did not reveal an overall survival benefit associated with pp in patients with ards requiring ecmo support. however, a subgroup analysis suggested that early initiation of pp may improve survival and should be considered in the design of a randomised controlled trial for further evaluation. supplementary information accompanies this paper at https://doi.org/ . /s - - - . efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for severe acute respiratory distress syndrome guidelines for adult respiratory failure effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis prone positioning in severe acute respiratory distress syndrome prolonged prone positioning under vv-ecmo is safe and improves oxygenation and respiratory compliance the effect of prone positioning in acute respiratory distress syndrome or acute lung injury: a meta-analysis. areas of uncertainty and recommendations for research prone position augments recruitment and prevents alveolar overinflation in acute lung injury complications of prone positioning during extracorporeal membrane oxygenation for respiratory failure: a systematic review prone positioning during veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults application of prone position in hypoxaemic patients supported by veno-venous ecmo prone positioning use to hasten veno-venous ecmo weaning in ards prone position during ecmo is safe and improves oxygenation combination of positioning therapy and venovenous extracorporeal membrane oxygenation in ards patients predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. the respiratory extracorporeal membrane oxygenation survival prediction (resp) score prognostic accuracy of the sofa score, sirs criteria, and qsofa score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit apache ii: a severity of disease classification system early fluid resuscitation and volume therapy in venoarterial extracorporeal membrane oxygenation deutsche gesellschaft für anästhesiologie und intensivmedizin (dgai). s -leitlinie -invasive beatmung und einsatz extrakorporaler verfahren bei akuter respiratorischer insuffizienz. . auflage mechanical ventilation to minimize progression of lung injury in acute respiratory failure a proportional hazards model for the subdistribution of a competing risk effect of prone positioning on cannula function and impaired oxygenation during extracorporeal circulation driving pressure and survival in the acute respiratory distress syndrome prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: time for a randomized trial publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. authors' contributions jr and tw contributed to the conception of the study; jr, cs, and tw contributed to the data collection; jr, vz, xb, pmb, dd, kk, ps, cm, mz, cb, dls, and tw contributed to the data analysis and interpretation; jr and tw drafted the manuscript; vz, xb, pmb, dd, kk, ps, cm, mz, cb, and dls revised the manuscript for important intellectual content. all authors approved the final version of the manuscript. none. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. not applicable. the authors declare that they have no competing interests.author details key: cord- - j vn authors: worku, elliott; gill, denzil; brodie, daniel; lorusso, roberto; combes, alain; shekar, kiran title: provision of ecpr during covid- : evidence, equity, and ethical dilemmas date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: j vn the use of extracorporeal cardiopulmonary resuscitation (ecpr) to restore circulation during cardiac arrest is a time-critical, resource-intensive intervention of unproven efficacy. the current covid- pandemic has brought additional complexity and significant barriers to the ongoing provision and implementation of ecpr services. the logistics of patient selection, expedient cannulation, healthcare worker safety, and post-resuscitation care must be weighed against the ethical considerations of providing an intervention of contentious benefit at a time when critical care resources are being overwhelmed by pandemic demand. extracorporeal cardiopulmonary resuscitation (ecpr) describes the emergent use of extracorporeal membrane oxygenation (ecmo) to restore circulation in patients during cardiac arrest [ ] . optimal patient selection, timing of initiation, post-ecpr patient management, and logistical feasibility of providing an ecpr service remain ongoing challenges to securing good outcomes [ , ] . among patients suffering either an out-of-hospital or an in-hospital cardiac arrest (ohca or ihca), few meet established and generally agreed upon eligibility criteria, and even fewer can be successfully cannulated for ecmo within acceptable timeframes. this makes ecpr a low-volume, high-risk, and resource-intensive intervention, of contentious benefit. with mainly observational data to support the use of ecpr, much remains to be studied in the field. the coronavirus disease (covid- ) pandemic poses additional challenges to the safe and appropriate use of ecpr. prioritising healthcare worker safety whilst facilitating expedient cannulation is fraught with complexity and presents a considerable barrier to the effective implementation of ecpr in this setting [ ] . appropriate candidate selection is a prerequisite for successful ecpr and is challenging under the best of circumstances [ ] . currently, identifying patients with the greatest potential to benefit from this resourceintense intervention is limited by the evolving understanding of the natural history of covid- and the ability to prognosticate at an individual patient level. finally, increased demand for critical care resources, the institution of crisis standards, and limitations on staffing and equipment are forcing the critical care community to confront the ethical boundaries between individual patient benefit, distributive justice, and resource allocation [ ] [ ] [ ] . rational decision-making must prevail in order to maximise both individual patient, and societal benefits. interventions pertaining to the resuscitation of a patient in cardiac arrest are time critical. when cardiac arrest occurs, blood flow ceases and the resulting "no-flow" state rapidly produces irreversible neurological and multiorgan damage, if not promptly ameliorated. conventional cpr (ccpr) produces a "low-flow" state that can temporarily sustain organ function. however, the longer the patient remains in cardiac arrest receiving ccpr, the less likely the patient is to achieve return of spontaneous circulation (rosc), even when advanced life support measures are applied [ ] . the application of ecmo to maintain organ perfusion is a well-established technique extrapolated from the use of cardiopulmonary bypass in cardiothoracic surgery, where an anesthetised patient is cannulated and mechanical circulatory support is initiated before the heart is arrested. in the case of ecpr, the patient is unconscious due to loss of cardiac output, and in this uncontrolled situation, the cannulation and establishment of mechanical circulatory support must occur rapidly. the american heart association (aha), in their update, support consideration of ecpr for those failing ccpr, where it can be "expeditiously implemented, and supported by skilled providers" [ ] . however, even with well-performed ecpr under non-pandemic conditions, the majority of patients will fail to survive with a good neurological outcome [ , ] . there are currently two main models of ecpr provision [ ] (fig. ). the first is in-hospital cannulation, whereby patients suffering an ihca or ohca who fail to achieve rosc with standard ccpr and advanced cardiac life support (acls) may be cannulated for ecpr. the site of cannulation is often the emergency department (ed), or cardiac catheterisation laboratory for ohca, or the intensive care unit (icu), operating theatre, or cardiac catheterisation laboratory for patients with ihca. the second is pre-hospital cannulation of patients suffering ohca refractory to acls and who are attended at scene by a mobile ecpr cannulation team. current data suggest that time to cannulation is a more important determinant of ecpr outcome than the site where cannulation occurs per se [ ] , and that stringent selection criteria applied rapidly at the scene may improve the yield of this intervention [ ] . identifying the group of patients who might benefit from ecpr is difficult. having a reversible (predominantly cardiac) underlying aetiology for the arrest [ ] , the receipt of effective bystander cpr, the presenting arrest rhythm, and the time to initiation of ecpr [ ] are important determinants of ecpr outcome [ ] . patients should also be free from precluding conditions, such as untreatable metastatic malignancy or life-limiting, endstage, chronic disease [ ] . the timing of transition from ccpr to the institution of ecpr is not universally agreed on. this conversion may be facilitated by the application of a mechanical cpr device to continue chest compressions whilst cannulation for ecpr is performed. following restoration of organ perfusion with ecpr, a targeted intervention to address the underlying aetiology of arrest must be performed. cardiac arrests of presumed cardiac origin have been disproportionately represented in ecpr studies; hence, high rates of angiography and subsequent percutaneous coronary intervention (pci) are often seen [ ] . this reflex resort to coronary angiography (intraarrest pci) may be challenged during the current pandemic, particularly in the absence of compelling st elevation [ , ] . severe acute respiratory syndrome coronavirus (sars-cov- ) may lead to a multisystem illness, covid- , in many patients. the majority of infected individuals either are asymptomatic or suffer a mild respiratory tract infection. approximately % of individuals with covid- will develop a more severe illness, and - % will develop critical illness characterised by severe respiratory failure with acute respiratory distress syndrome (ards) [ ] . additionally, sars-cov- can directly infect and impair other organ systems including the cardiac, gastrointestinal, renal, and central nervous systems, with the angiotensin-converting enzyme (ace ) receptor possibly implicated in viral tropism for these tissues. other sequelae of covid- disease may include a prothrombotic state, or immunodepression with superinfection, which in turn may potentiate acute pulmonary embolism, with ensuing acute cor pulmonale, or septiclike circulatory compromise. the number of critically unwell patients with covid- who require icu admission and organ support has overwhelmed health services in many countries globally, necessitating the rationing of critical care resources [ ] . ecpr is complex, and efficient deployment relies on finely honed processes that may be significantly impacted by pandemic conditions. in acknowledging these circumstances, the current guidance on ecpr provided by elso [ ] states the following: a) centres with lesser experience or without established ecpr programmes are discouraged from initiating ecpr for ohca during surge situations. b) experienced centres may offer ecpr for ihca for highly selected non-covid- patients depending on resource availability, whilst ecpr use in covid- -positive patients requires reflection on the risk-benefit ratio. c) emergency conversion of venovenous ecmo to venoarterial ecmo in the setting of a cardiac arrest in a patient receiving venovenous ecmo or during cannulation is not recommended-due to the poor outcomes anticipated. there are two scenarios that might be used to describe the aetiology of cardiac arrest during the covid- pandemic. first, a cardiac arrest occurring in a patient who does not have covid- would be presumed to be due to one of the currently understood aetiologies of ohca and ihca. these patients would be eligible for consideration of ecpr based on currently used criteria where resources are not constrained by the pandemic. the second is cardiac arrest in a patient who is known, or suspected, to have covid- . in this case, the aetiology of cardiac arrest may be related to the effects of the sars-cov- virus, as abovementioned, or the virus may simply be a bystander. in all circumstances, as community transmission of covid- increases, it will become difficult to differentiate patients at presentation with respect to infectious status and the default will be a presumption of positivity. irrespective of their infectious status and the aetiology of the cardiac arrest, the resource constraints imposed by the pandemic may limit usual processes of care. delays in ccpr initiation due to the reluctance of members of the public and healthcare workers to initiate out-of-hospital resuscitation attempts, fig. current models for ecpr provision in ohca. in all comers with ohca, the vast majority will be pronounced dead at scene or on arrival to hospital. a in select patients with refractory cardiac arrest, ecpr may be advocated; this demands consideration of the predominant arrest rhythm (shockable preferable), the presence of bystander cpr, and the logistics of cannulation, icu capacity, and availability of services such as pci to determine and treat potential aetiologies. b expedient cannulation and establishment of extracorporeal perfusion is a requisite of an effective ecpr; for ohca, this may occur: (i) on-scene cannulation by mobile ecmo practitioners and (ii) rapid retrieval to ecpr hospital recognising those patients who might benefit from ecpr, requirements for donning personal protective equipment (ppe), impaired ambulance response times, and lack of critical care resources, may preclude the use of ecpr even in those who would otherwise be eligible. hypoxaemic respiratory failure leading to cardiac arrest appears to be common in covid- patients. in a retrospective cohort study of patients suffering ihca in wuhan, china, . % of arrests were due to a respiratory aetiology. the vast majority occurred outside of an icu setting, and shockable rhythms were observed in only . % of this cohort. survival outcomes were dismal in this cohort with only one patient surviving to days with a favourable neurologic outcome (cerebral performance category (cpc) [ , , ] ). it is also reported that the interplay between patient comorbidities, in particular cardiovascular risk factors, and the aetiologic virus may give rise to a range of cardiovascular pathological insults [ ] . acute myocardial infarction, myocarditis, and coronary spasm fuelled by hyperinflammation, multiorgan dysfunction, thrombotic phenomena, and severe hypoxaemia resulting in cardiac arrest have been described [ ] . cardiac arrhythmias are also frequently reported and may reflect direct effects of the disease or cardiotoxicity from agents [ ] repurposed to treat covid- . in a true surge crisis, critical care demand outstrips capacity, and it becomes untenable to provide ecpr and post-resuscitative support. establishing even basic ccpr may be hindered by delayed response times, time to allow ppe donning, and system pressures diverting the resuscitation team. exceptions would include patients who arrest during coronary angiography, for instance, in which case rapid cannulation is possible, the aetiology may be more amenable to reversal, and there is the added benefit of advanced imaging available to confirm cannula placement should ecpr be initiated. continuing access to ecpr during the coivd- pandemic requires adherence to surge-specific protocols and prompt involvement of senior decision-makers at the time of an arrest in order to promote acceptable outcomes. local tools could be developed to aid with rapid assessment of ecpr candidacy and feasibility [ ] . as with ccpr, ad hoc decision-making regarding ecpr should be discouraged. goals of care and resuscitation status should be addressed transparently with patients and surrogate decision-makers, so that any limitations dictated by patient or system factors are explicit. the nature of ecpr often precludes such discussions from happening in real-time, only adding to the burden of responsibility on clinicians. the ecpr team response in covid- (fig. ) is complicated by the need for ppe arising from the heightened risk of healthcare worker infection and contamination of clinical areas and equipment by aerosolised fomites [ ] and blood [ ] . provision of ecpr should ideally be an interdisciplinary decision and is best prepared for via high-fidelity simulation and streamlined cannulation teams [ , ] . for example, situations such as ecpr in the covid- patient who is in the prone position would need to be anticipated and rehearsed, if such a scenario is to be considered. there also needs to be an appreciation for wider system demands. for example, there are critical blood product shortages (due in part to a shrinking pool of healthy donors), and so conservation strategies such as percutaneous over surgical cannulation are important [ ] . patient transfer after ecpr necessitates predesignated egress routes from the place of cannulation to other destinations, to mitigate the risks of crosscontamination of "clean" areas. ideally, in already experienced ecmo centres, patients treated for covid- disease and related complications should have a clearly declared escalation status, including candidacy for ecmo support and ecpr if the need were to arise. such decisions must take into account the local protocols, the equipment availability, and the readiness of the system to accommodate sudden and dramatically increased demands. a fundamental principle underpinning all pandemic responses is the maximisation of benefit from scarce resources [ ] . resource scarcity and resource saturation are fluid judgements, relying on continual cycles of appraisal, integrating real-time data, and epidemiological projections [ ] . maximising benefit refers not only to enhancing survival in individuals, but also to extending this opportunity to as many patients as possible or most appropriate candidates to benefit from. ecpr exacts a heavy toll on equipment (membrane oxygenator and ecmo circuit, blood products, ultrasound devices, and ppe among them) and staff (intensified nursing and other key supports, ecmo specialists, senior intensivist oversight, and others). personnel siphoned to support ecpr might be better deployed caring for several other less critical patients with a better chance of helping a greater number; similarly, the ecmo circuit may provide respiratory support for a patient with single organ dysfunction. beyond the immediate intervention, there are ongoing costs to convalescence. although survivors of ecpr may demonstrate favourable neurologic outcome, the covid- cohort cannot be assumed to be typical. the potential for generating dependent survivors is a burden ecpr may impose, and the benefits of ecpr may be overestimated in the covid- cohort. there may be fig. possible management of the confirmed or suspected covid- -positive patient with oohca. a bystander ccpr, with risk of aerosolisation and viral transmission: in many cases, this may not be performed on patients with known infectious status. b ambulance service provides defibrillation and early airway securement to minimise aerosol generation. time to don ppe and elevated system demands may delay attendance. in sustained non-shockable cardiac arrest, it may be appropriate to curtail resuscitation and avoid hospital transfer. c e-cpr if appropriate, in an isolated negative pressure environment with mechanical compressions. ecmo team should be in high-level ppe including papr. in non-ecpr centres, the patient may proceed to coronary angiography if appropriate intra-arrest or more typically post-rosc. inter-hospital transfer for ecpr or pci would not be routine. d icu admission is contingent upon patient prognosis and system capacity. it may be reasonable to admit only if rosc has been achieved. good neurological survival remains the desired outcome. patients may receive ttm/hypothermia and ongoing mechanical circulatory support for an agreed duration. outcomes include recovery, wlst, or brain death. organ donation may only be considered in patients confirmed to be covid- negative. ccpr, compression only cpr; ppe, personal protective equipment; ttm, targeted temperature management; wlst, withdrawal of life-sustaining therapy survivors with ecpr during the coivd- pandemic, but at what individual and health opportunity cost? if resources are committed to ecpr early during a surge, ongoing availability of icu resources may be further limited to other patients, infected or not [ ] , who have a greater probability of benefit. whilst it is important to support the individuals' right to treatment, equity during a pandemic dictates a process of triage and prioritisation, ensuring that healthcare allocation is contingent on anticipated utility and maximum benefit. many scenarios may arise without a clear right answer. best judgement necessarily depends on dispassionate, open communication, triage, and frequent re-evaluation of the healthcare landscape. the right to withhold life-sustaining treatment varies globally [ ] . in denmark, ccpr initiation by paramedics is a mandatory practice as the absence of a circulation defines a patient with cardiac arrest, not death [ ] . in some jurisdictions, it is only when "inconsistent with good medical practice" that it is permissible to withdraw therapy without consent [ ] . with respect to life-sustaining treatment, the concept of futility is illdefined, and often there is poor agreement between the physician and patient or surrogate decision-maker. furthermore, public perception of ccpr is skewed through media portrayals. the most appropriate argument for withholding or withdrawing ccpr and ecpr in covid- patients must be non-maleficence to the patient and others. it is accepted that extended resuscitation can be curtailed during crises, and since ecpr is not yet the standard of resuscitative care, whether access to ecpr may be refused is not nearly as contentious as reluctance to provide ccpr. a number of health systems are declining resuscitation of covid- -positive patients as a rule [ ] , discerning risks to the system and healthcare workers from potential aerosolisation to exceed individual benefit of attempted resuscitation. although resuscitation is sometimes performed to alleviate family suffering, by providing assurances that "everything was done", this practice should be questioned during a crisis. emotions should be tempered, and objectivity should dictate actions [ ] . some centres routinely mandate ethicist consultations in the withdrawal of ecmo support [ ] . the urgency of ecpr necessitates expediency, so limited opportunities exist to fully explore outcome scenarios with surrogate decision-makers at the time of cannulation; the decision to offer and subsequently limit ecpr rests heavily on the clinicians' shoulders. ecpr initiation is an organisational decision, requiring support from multiple specialties. this impacts on attendance to other clinical priorities, risks to other hospitalised patients, and to the hospital infrastructure; therefore, cannulation should be by consensus; equally, withdrawal should incorporate multiple stakeholders. fairness and equity dictate that objective criteria motivate both treatment escalation and withdrawal of life-sustaining therapies. where ecpr has been offered, evolving multiorgan dysfunction or signs of poor neurological recovery must prompt the treating team to approach the subject of withdrawal [ ] , in systems where this is considered acceptable, not only to prevent burdensome treatment to the patient, but also to make available resources for those who may yet benefit. these hard truths would ideally be explicit before cannulation commences and will require empathy and transparency with families [ ] . staff morale is an important but secondary consideration, and both moral and psychological injuries [ ] to the workforce are significant risks when embarking upon interventions with limited potential for therapeutic benefit. observational data suggests that ecpr provides an improved opportunity for favourable neurological survival in highly selected patients experiencing cardiac arrest compared with ccpr. whilst there is a need for prospective study and high-quality randomised trials in this area [ ] , the current covid- pandemic presents practical and ethical challenges to the ongoing provision and implementation ecpr programmes. at a time when critical care faces heavy constraints, it is important to work within ethical and legal frameworks to espouse equity and consistency in healthcare allocation, remembering not to inadvertently disadvantage non-covid- patients. the 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compared with sars-cov- covid- may transmit through aerosol. ireland: ir protecting health-care workers from subclinical coronavirus infection tackling covid- : are the costs worth the benefits? considerations for ventilator triage during the covid- pandemic termination of prehospital resuscitative efforts: a study of documentation on ethical considerations at the scene the legal role of medical professionals in decisions to withhold or withdraw life-sustaining treatment: part (queensland) covid- : doctors are told not to perform cpr on patients in cardiac arrest understanding ethical decisions for patients on extracorporeal life support managing mental health challenges faced by healthcare workers during covid- pandemic early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: design and rationale of the inception trial publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations ks acknowledges research support from the metro north hospital and health service. authors' contributions db, ks, and rl conceptualised the paper. ew wrote the first draft and coordinated the writing process. dg contributed substantially to the writing of the manuscript and designed the figures. db, ks, rl, and ac critically evaluated and made significant edits to the subsequent versions of the manuscript. all authors approved the final version of the manuscript prior to submission. not applicable. not applicable.availability of data and materials not applicable.ethics approval and consent to participate not applicable to this work. competing interests db is on the medical advisory boards for breethe, xenios, and hemovent and is a past medical advisory board member for baxter and alung technologies; he is currently on the trial steering committee for the vent-avoid trial sponsored by alung technologies; he is a member of the board of directors of elso and is chairman of the executive committee of ecm-onet. rl is a consultant for medtronic and livanova, and a member of the medical advisory board of eurosets and pulsecath. ac reports grants and personal fees from getinge and baxter; he was the president of euroelso and is a member of the executive and scientific committees of the international ecmo network (ecmonet). ks is a member of the ecmonet scientific committee and the asia-pacific elso steering and educational committees and is the research lead for the elso educational taskforce (ecmoed). key: cord- -uvajk ea authors: ahmadi, zargham hossein; jahangirifard, alireza; farzanegan, behrooz; tabarsi, payam; abtahian, zahra; abedini, atefeh; sharifi, mehrzad; jadbabaei, amir naser; mafhumi, yadollah; moslem, ali; sistani, marjan; yousefian, sahar; saffaei, ali; dastan, farzaneh title: extracorporeal membrane oxygenation and covid‐ : the causes of failure date: - - journal: j card surg doi: . /jocs. sha: doc_id: cord_uid: uvajk ea introduction: venovenous extracorporeal membrane oxygenation (vv‐ecmo) is a therapeutic strategy for the coronavirus disease (covid‐ ) induced acute respiratory distress syndrome (ards). there are inconclusive data in this regard and causes of vv‐ecmo failure are not yet understood well. case series: here, seven patients with covid‐ ‐induced ards who underwent vv‐ecmo introduced and causes of vv‐ecmo failure discussed. medical records of seven covid‐ patients treated with vv‐ecmo were retrospectively evaluated to determine the clinical outcomes of vv‐ecmo. oxygenator failure occurred in four patients whom needed to oxygenator replacement. successful vv‐ecmo decannulation was done in three patients, however finally one patient survived. conclusions: hypercoagulability state and oxygenator failure were the most main etiologies for vv‐ecmo failure in our study. all patients with covid‐ undergoing vv‐ecmo should be monitored for such problems and highly specialized healthcare team should monitor the patients during vv‐ecmo. and middle east respiratory syndrome coronavirus-related ards. since the efficacy and safety of vv-ecmo in patients with covid- -induced ards are still unclear, here we report seven patients with covid- induced ards who underwent vv-ecmo. this is a single-center study, based on a retrospective cohort analysis of cases treated at the dr. masih daneshvari hospital, tehran, iran, which is the main referral center for patients with covid- in iran. the vv-ecmo procedure was the same for all patients. in all patients with refractory hypoxemia not responding to noninvasive ventilation, endotracheal intubation was performed, using low tidal volume, with a maximum plateau airway pressure of cm h o. when necessary, the respiratory rate was increased to a maximum of breath/min, which was the mainstay of lung protective ventilation. patients with a pao / fio ratio inferior to for hours, or a pao /fio ratio inferior to for hours, were candidate for vv-ecmo, regardless of having high positive end-expiratory pressure and neuromuscular blockage. transthoracic echocardiography was performed, and if left ventricular ejection fraction was less than %, va-ecmo would be applied. the console of the vv-ecmo was centrifugal pump system (liva nova deutschland gmbh, münchen, germany). the oxygenator was eos hollow fiber oxygenator intended for long duration procedures (liva nova, mirandola, modena, italy). the drainage femoral cannula was rap fv two stage out of (liva nova), which was inserted by close seldinger's maneuver in the left or right femoral vein. the return cannula was a -f easy flow duo arterial femoral cannula (liva nova), inserted by close seldinger's maneuver in the right internal jugular vein. the position of the cannula was verified by chest x-ray, as well as by evaluating the efficacy of the system, by increasing the arterial oxygen saturation and partial pressure of arterial oxygen. the bolus dose of heparin ( units/kg) was injected before cannulation. ecmo was initiated if activated clotting time (act) was in the range of to seconds. the heparin infusion would be continued at dose of to units/kg to maintain aptt between to seconds. the rate of infusion was adjusted according to aptt result, which was checked every hours. during the index period, patients with severe ards were referred to our institution. we evaluated seven covid- cases that underwent vv-ecmo because of severe ards. the median age of patients at the time of hospitalization was years (range, - years). one patient was female and the rest were male. all patients complained of high-grade fever, cough, and dyspnea at admission time. the median time from symptom onset to hospitalization was days (range, - days). all patients had at least one underlying disease. a combination of hydroxychloroquine and lopinavir/ritonavir were administered to all patients according to iranian national guideline. during the implantation of vv-ecmo, all patients had severe hypoxemia (peripheral oxygen saturation between %- %). only patient was discharged with a stable condition. clotting formation in the oxygenator was seen in four patients, in first -day of vv-ecmo. patients' details are summarized in table and the chest x-ray findings of patients at first day of vv-ecmo starting is shown in figure . a -year-old male nurse with severe covid- pneumonia was referred to the hospital. he complained of fever, cough, and dyspnea from days before admission. for days, he was intubated for invasive mechanical ventilation due to severe ards. his medical history showed a diagnosis of influenza h n months before. he developed a worsening hypoxemia refractory to conventional ventilation. chest x-ray showed a severe bilateral infiltration in both upper and lower lobes; therefore, he was treated with vv-ecmo. the patient died after days because of sudden hypoxia due to oxygenator failure of the vv-ecmo, causing clotting and subsequent cardiac arrest. a -year-old man diagnosed with severe covid- pneumonia was referred to the hospital. he complained of fever, cough, dyspnea, myalgia, and diarrhea from days before. at admission, patient had severe hypoxemia and he was intubated for invasive mechanical ventilation due to ards. chest x-ray showed a severe bilateral infiltration in both upper and lower lobes. after days of invasive mechanical ventilation, hypoxemia persisted. the patient became oliguric (urine output less than ml/h) and developed hemodynamic instability. serum creatinine increased to . mg/dl. he was treated with vv-ecmo and continuous renal replacement therapy. then, oxygen saturation increased to %, whereas creatinine decreased to . mg/dl. however, after days, the serum creatinine increased again from . mg/dl to . mg/dl, serum lactate dehydrogenase (ldh) increased to u/l, hemoglobin decreased to . mg/dl, and platelet decreased to /l. the patient died due to multisystem organ failure. a -year-old woman with severe covid- pneumonia was referred to the hospital. she complained of fever, cough, dyspnea, myalgia, and diarrhea from days before admission. dyspnea persisted for the next days and chest x-ray revealed progressive infiltration. because of severe persistent hypoxemia, the patient was intubated for invasive mechanical ventilation; however, due to progressive hypoxemia, the vv-ecmo was applied days later, and oxygen saturation increased to %. in the th day of vv-ecmo, she showed gradual hypoxia and elevated d-dimer, and the oxygenator was changed in the th day. hypoxia was reversed and the patient's condition improved. after days, she was weaned of vv-ecmo successfully. however, hours after the removal of vv-ecmo, she a -year-old physician diagnosed with severe covid- pneumonia was referred to the hospital. he complained of fever, cough, dyspnea, and myalgia from days before admission. he was the chest x-ray imaging of patients at first day of venovenous extracorporeal membrane oxygenation starting intubated due to severe ards. chest x-ray showed a severe bilateral infiltration in both upper and lower lobes. the hypoxemia and lung infiltration progressed during hospitalization; therefore, the patient was treated with vv-ecm. oxygen saturation increased to %. on the th day of vv-ecmo, the oxygenator was changed due to decreased oxygenation and hypercarbia. after days, the patient's clinical condition improved and no metabolic disturbances occurred. he was decannulated from extracorporeal support, although he developed convulsions after decannulation of vv-ecmo. convulsions were not controlled by pharmacological interventions and extensive cerebrovascular accident happened and finally the patient died despite all efforts. a -year-old man, diagnosed with severe covid- pneumonia was referred to the hospital. he complained of fever, cough, dyspnea, and myalgia from days before admission. after days of hospitalization, hypoxemia occurred, and oxygen saturation decreased to %. chest x-ray showed a severe bilateral infiltration in both upper and lower lobes. hence, the patient was intubated for invasive mechanical ventilation due to severe hypoxemia. however, hypoxemia persisted and he was treated with vv-ecmo. following vv-ecmo, oxygen saturation increased to %. on the th day of vv-ecmo, oxygen saturation decreased and partial pressure of carbon dioxide increased. the oxygenator was changed immediately and the aptt was maintained in therapeutic range. the patient tolerated days of vv-ecmo, and no significant complications occurred. the tracheotomy was performed and patient was transferred to ward under acceptable medical conditions. the management of this patient was improved in comparison with previous cases due to achievement of more experiences. coagulopathies and oxygenator failure did not occur and finally the patient was discharged after days. in some patients with ards, positive pressure ventilation may worsen the clinical condition and even multisystem organ failure may occur. vv-ecmo will benefit a selected patient population, such as those with severe ards. vv-ecmo is a highly specialized and very expensive form of advance life support and there are some guidelines, such as emprove protocol, with proven outcomes in this regard. the treatment of severe ards due to covid- with vv-ecmo remains a challenge and controversial. , since some studies showed a higher mortality rate, compared with patients receiving only conventional respiratory care ( % vs %, respectively). , the most important finding in these cases was the hypercoagulability state, with high rate of oxygenator failure, and the necessity to change it, which occurred at least twice than in other studies. on the other hand, all patients were treated with continuous intravenous heparin to maintaining the aptt between and seconds. also, according to the results, our protocol changed and we suggest that for anticoagulation management of patients with covid- under ecmo, aptt should not be used. instead of aptt, act should be monitored and kept between and seconds. we examined this protocol in two patients with satisfactory results. oxygenator dysfunction leading to oxygenator replacement was seen in % to % of vv-ecmo patients. nevertheless, such rate was unusual, particularly among those without hepatic failure. the fourth patient developed hepatic failure, probably due to a hypercoagulability state. the persistent hypoxemia in most patients might lead to rapid clinical deterioration, multi system organ failure and death. another main issue was the late diagnosis of oxygenator failure, due to excess work load of nurses. on the basis of our study, and considering the evidence from chinese patients, we think that the hypercoagulability state might be a phenomenon among severe cases of covid- that requires to be carefully monitored. previous studies showed that the mortality rate related to vv-ecmo could be reduced if vv-ecmo is introduced within the first days of mechanical ventilation. in our cases, the high rate of mortality may be explained by the delayed implantation of vv-ecmo in patients under critical conditions. future investigations should consider that since vv-ecmo is unlikely to improve patients' overall outcomes, if potentially fatal complications cannot be prevented. hypercoagulability state and oxygenator failure were the most important etiologies for vv-ecmo failure in covid- patients with severe ards in our study. all patients with covid- undergoing vv-ecmo should be monitored for such a phenomenon and managed meticulously to improve their survival. moreover, the implementation of highly specialized healthcare team, state-of-the-art medical devices, and diagnostic laboratories are deemed indicated for enhancing care delivery. payam tabarsi yadollah mafhumi sahar yousefian risk factors for severity and mortality in adult covid- inpatients in wuhan continues renal replacement therapy (crrt) with disposable hemoperfusion cartridge: a promising option for severe covid- planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases extracorporeal membrane oxygenation for pandemic influenza a(h n )-induced acute respiratory distress syndrome a fourteen-day experience with coronavirus disease covid- ) induced acute respiratory distress syndrome (ards): an iranian treatment protocol the impact of an advanced ecmo program on traumatically injured patients ecmo for ards due to covid- association between hypoxemia and mortality in patients with covid- bleeding, thrombosis, and transfusion with two heparin anticoagulation protocols in venoarterial ecmo patients heparin-sparing anticoagulation strategies are viable options for patients on veno-venous ecmo abo blood group and risk of thromboembolic and arterial disease abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia mechanical ventilation during extracorporeal membrane oxygenation in patients with acute severe respiratory failure the authors would like to thank dr. yousef rezaei, ms. mandana hosseinzadeh, and miss sepideh nazari for their sincere cooperations. the authors declare that there are no conflict of interests. all authors collected the clinical data, drafted and revised the manuscript. ahmadi et al. | https://orcid.org/ - - - xfarzaneh dastan http://orcid.org/ - - - key: cord- - ah cdph authors: bartlett, robert h.; ogino, mark t.; brodie, daniel; mcmullan, david m.; lorusso, roberto; maclaren, graeme; stead, christine m.; rycus, peter; fraser, john f.; belohlavek, jan; salazar, leonardo; mehta, yatin; raman, lakshmi; paden, matthew l. title: initial elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure date: - - journal: asaio j doi: . /mat. sha: doc_id: cord_uid: ah cdph disclaimer: ecmo has, and will certainly continue, to play a role in the management of covid- patients. it should be emphasized that this initial guidance is based on the current best evidence for ecmo use during this pandemic. guidance documents addressing additional portions of ecmo care are currently being assembled for rapid publication and distribution to ecmo centers worldwide. disclaimer: ecmo has, and will certainly continue, to play a role in the management of covid- patients. it should be emphasized that this initial guidance is based on the current best evidence for ecmo use during this pandemic. guidance documents addressing additional portions of ecmo care are currently being assembled for rapid publication and distribution to ecmo centers worldwide. the extracorporeal life support organization (elso) and all of the elso worldwide chapters have prepared this document to describe when and how to use extracorporeal membrane oxygenation (ecmo) in covid- patients during this pandemic. it is a consensus guideline intended for experienced ecmo centers. covid- is a disease caused by the novel sars-cov- virus which appeared in december and is now a worldwide pandemic. because it is a new viral disease, this guidance document is based on limited experience and written with the intention to be updated frequently as new information becomes available. a link to the latest version of this document will be found at http://covid .elso.org. although most covid- patients have moderate symptoms and recover quickly, some patients develop severe respiratory failure and acute respiratory distress syndrome (ards) requiring intensive care admission. the mortality in covid- patients who require mechanical ventilation is high. extracorporeal membrane oxygenation can be lifesaving in patients with severe forms of ards, or refractory cardio-circulatory compromise. initial experience in japan and south korea with ecmo in > covid- cases has had survivors, with many still receiving treatment. an overview article in lancet respiratory medicine examines the role of ecmo and ecmo centers during the covid- pandemic. additionally, guides detailing the requirements for an ecmo program are available in both the medical literature and the elso website. the society of critical care medicine also has promulgated guidelines for the management of covid- patients and recommends the use of ecmo when conventional management fails. due to the intensive hospital resource utilization, substantial staff training, and multidisciplinary needs associated with starting an ecmo program, elso recommends against starting new ecmo centers for the sole purpose of treating patients with covid- . as mentioned in a recent article by elso leaders in jama, for inexperienced centers, "ecmo is not a therapy to be rushed to the front lines when all resources are stretched during a pandemic." a list of experienced ecmo centers is provided on the elso website. during the covid- surge, it is reasonable to concentrate those patients with the greatest chance of benefit from receiving ecmo in a hospital where an experienced ecmo team is available. extracorporeal membrane oxygenation indications, access, and management are described in the elso guidance for adult respiratory and cardiac failure on the elso web site (https:// elso.org). extracorporeal membrane oxygenation is indicated in patients who have a high risk of mortality. there are several ways to measure mortality risk in ards. all include pao /fio below , despite and after optimal care. for adult respiratory failure, the recently published eolia trial contains three indications that define severe ards where ecmo may be useful. many standardized algorithms for ards therapies, such as figure below, have been published and may be of aid to clinicians. when patients meet indications, ecmo should be initiated immediately in an experienced center, and not days later. because the use of ecmo for covid- is occurring during a pandemic which can overwhelm hospital resources, unique considerations for ecmo in covid- patients are: this decision is a local (hospital and regional) responsibility. it is a case by case decision that should be reassessed regularly based on overall patient load, staffing, and other resource constraints, as well as local governmental, regulatory or hospital policies. if the hospital must commit all resources to other patients, then ecmo should not be considered until the resources stabilize. if the hospital feels that ecmo can be safely provided, then it should be offered to patients with a good prognosis with the use of ecmo, and perhaps to other patients who qualify for ecmo support (see below). use of ecmo in patients with a combination of advanced age, multiple co-morbidities, or multiple organ failure should be rare. based on current medical evidence and outcomes, it is not appropriate to state "ecmo will never be considered for covid- patients." due to the complexity and extensive team training associated with doing ecmo during cpr (e-cpr), centers who do not currently provide these services, should not initiate programs during times of limited resources. inexperienced ecmo centers should consider whether to continue these programs during resource-limited times. at experienced centers, e-cpr may be considered for in-hospital cardiac arrest depending on resource availability. however, in patients with covid- , the potential for cross-contamination of staff and the use of personal protective equipment by multiple practitioners when in short supply, should be considered in the risk-to-benefit ratio of performing e-cpr. initiating e-cpr in patients with multiple co-morbidities or multiple organ failure should be rare. during the covid- pandemic? understanding hospital resource limitations as above, standard ecmo should continue when that is possibly related to overall hospital resources. exclusion used in the eolia trial can be taken as a conservative approach to contraindications to ecmo. ∫eg neuromuscular blockade, high peep strategy, inhaled pulmonary vasodilators, recruitment maneuvers, high-frequency oscillatory ventilation. ¶recommend early ecmo as per eolia trial criteria; salvage ecmo, which involves deferral of ecmo initiation until further decompensation (as in the crossovers to ecmo in the eolia control group), is not supported by the evidence but might be preferable to not initiating ecmo at all in such patients. peep, positive end-expiratory pressure; pao :ho , ratio of partial pressure of oxygen in arterial blood to the fractional concentration of oxygen in inspired air; ecmo, extracorporeal membrane oxygenation; paco , partial pressure of carbon dioxide in arterial blood. younger patients with minor or no co-morbidities are the highest priority while resources are limited. health care workers are a high priority. it should be acknowledged that this is a dynamic prioritization. as resources change, priorities should shift based on what can be safely done in the hospital-specific setting. standard contraindications apply terminal disease, severe central nervous system damage, do not resuscitate status, or advanced directives refusing such therapy. . exclusions for covid- during limited resources are hospital or region-specific. . because prognosis is worse with comorbidity, patients with significant co-morbidities should be excluded. . because prognosis is worse with age, older age should be considered when balancing resource availability with the potential to improve outcomes. . because prognosis is worse with time on invasive mechanical ventilation, patients on mechanical ventilation greater than days (these are general guidelines which may not apply to specific covid- patients depending on local circumstances) should be excluded. . renal failure is not an exclusion. . use of ecmo in patients with a combination of advanced age, multiple co-morbidities, or multiple organ failure should be rare. standard covid- precautions as recommended by who and national health organizations should be used. there are currently no special precautions recommended for blood contact. not all patients will improve with ecmo support. as is standard with usual ecmo care, clinicians should be continuously evaluating when ecmo no longer provides a positive benefit:risk ratio and should at that point return to conventional management regardless of how long the patient has been on ecmo. during times of limited resources, this becomes especially important and while the definition will be hospital or region-specific, observing no lung or cardiac recovery after approximately days (these are general guidelines which may not apply to specific covid- patients depending on local circumstances) on ecmo can be considered futile, and the patient can be returned to conventional management (note: for situations where withdrawal of life-sustaining therapies is not an option, this change of management does not constitute withdrawal.). what is the incidence of cardiac failure and how is it managed? as in any patient, cardiac failure is defined as sustained hypotension despite other management. failure is confirmed and measured by physiologic parameters and echocardiography. va access is indicated, perhaps in the form of v-va. therefore, timely echocardiographic assessment in the presence of any clinical suspicion of cardiac dysfunction or sign of circulatory compromise should be undertaken. for elso member centers, when you use ecmo for covid- , please enter your patient in the registry at the time they go on (and later when discharged). early registry entry allows elso to be able to provide member centers with real-time and up to date outcome and complication data. centers that are using ecmo and are not elso members are encouraged to join elso and enter covid- cases. membership fee is waived during this pandemic. planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases international ecmo network (ecmonet) and the extracorporeal life support organization (elso): position paper for the organization of ecmo programs for cardiac failure in adults extracorporeal life support organization surviving sepsis campaign covid- guidelines preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation extracorporeal life support organization extracorporeal membrane oxygenation for severe acute respiratory distress syndrome ecmo for ards: from salvage to standard of care? key: cord- - duu c n authors: maclaren, graeme; combes, alain; brodie, daniel title: what’s new in ecmo for covid- ? date: - - journal: intensive care med doi: . /s - - -z sha: doc_id: cord_uid: duu c n nan the first studies of coronavirus disease (covid- ) from china reported high mortality rates in patients supported with extracorporeal membrane oxygenation (ecmo) [ ]. very little was known about the natural history of the virus, prompting both speculation about the precise role of ecmo [ ] and recommendations for its use [ , ] . many clinicians were concerned about using high-cost, resource-intensive therapies for a small, select proportion of critically ill patients if national healthcare systems were in danger of being overwhelmed. it was unclear whether the reasons underlying these initial, apparently high mortality rates related to the pathophysiology of the virus itself or the use of ecmo by overburdened clinicians in suboptimal circumstances. data has recently emerged outlining the potential role of ecmo for covid- with greater clarity. a multicentre french study captured the early experience with critically ill covid- patients after the first wave of the pandemic hit western europe [ ]. eightythree ( %) of intensive care patients with covid- -related acute respiratory distress syndrome (ards) received ecmo and were ultimately assessed to have an estimated probability of -day mortality of % ( % ci - ). the patients were similar in many regards to those in the 'ecmo to rescue lung injury in severe ards' (eolia) trial [ ] , with a median partial pressure of arterial oxygen to fraction of inspired oxygen (pao / fio ) ratio of (iqr - ) prior to ecmo. they were also managed along similar evidence-based principles [ ] to the eolia cohorts and % received prone positioning prior to ecmo. bleeding and thrombotic events were common, with % of patients suffering a major bleeding episode and % having pulmonary emboli during ecmo. in comparison, no patients in the eolia trial were reported to have pulmonary emboli during ecmo. this apparent increase in the risk of life-threatening thromboembolism has also been documented in critically ill covid- patients not receiving ecmo [ ] . nosocomial infections were also frequently seen. eightyseven percent of patients developed ventilator-associated pneumonia and % had bacteraemia. this report provided insights into the use of ecmo for covid- in experienced centres, including those which had participated in the eolia trial, and had consistent protocols and standardized ards management practices in place prior to the pandemic. the largest report to date from the extracorporeal life support organization (elso) registry included patients from centres across countries [ ] . data on patients with covid- supported with ecmo showed an estimated cumulative incidence of in-hospital mortality days after ecmo initiation of % ( % ci - ). in those who had a final disposition of death or hospital discharge, % had died. this report detailed patients with covid- supported with ecmo regardless of clinical indication, not only those with ards. six percent of patients received ecmo for mechanical circulatory support, which was associated with higher mortality (hazard ratio (hr) . , % ci . - . ). a higher risk of mortality was also seen in those over years old (hr . , % ci . - . ). median pao /fio ratio prior to cannulation was (iqr - ) and % had a trial of prone positioning prior to ecmo initiation. there were no significant differences in the rates of circuit clot or malfunction when compared to centre data from the registry, once normalized for the longer median times on ecmo in the covid- patients. some reports highlighted the use of relatively novel management strategies consisting of bundled treatment elements, each of which had been applied in patients prior to the pandemic, but were now being trialed more systematically in patients with covid- . for example, *correspondence: gmaclaren@iinet.net.au in the multicentre french study cited earlier [ ], % of the patients were nursed in the prone position during ecmo. it is unknown whether this practice leads to better outcomes but there is preliminary evidence suggesting that it may be associated with lower mortality [ , ]. an american report described covid- patients meeting eolia entry criteria, % of whom received prone positioning prior to ecmo initiation. these patients were all cannulated for ecmo using a specific dual-lumen cannula (protek-duo tandemheart cannula, cardiacassist inc, pittsburgh, pa) inserted into the pulmonary artery under echocardiographic guidance, providing venovenous ecmo with right ventricular mechanical circulatory support by draining right atrial blood and returning oxygenated blood directly into the pulmonary artery [ ] . patients were able to be weaned from invasive mechanical ventilation during ecmo a mean of days after ecmo initiation and physical therapy was provided thereafter. six ( %) patients had died and ( %) were discharged at the time of the report. despite this encouraging early signal that the majority of selected patients with covid- severe enough to require ecmo survive, many uncertainties remain (table ) . although the tropism for severe respiratory failure is obvious, the virus can cause disease in other organ systems, the long-term effects of which are unknown [ ] . in some other ecmo patient populations, there is a small but demonstrable risk of late mortality more than days following initiation of ecmo, as well as risks of physical and psychological debility. further study will be needed to ascertain the proportion of patients who suffer from these late complications after ecmo in the setting of covid- and what can be done to mitigate them. in summary, ecmo appears to have a role in the management of adult patients with covid- who suffer from ards refractory to other management strategies. there is greater uncertainty about the role of ecmo in other populations with covid- , such as patients requiring mechanical circulatory support, extracorporeal cardiopulmonary resuscitation (ecpr) [ ] , or those with multisystem inflammatory syndrome in children. nonetheless, preliminary data appear to support the use of ecmo in many of these conditions as well [ , ] . the initial concerns that ecmo for covid- was associated with unacceptable short-term outcomes have been assuaged, at least when ecmo is used in experienced centres. what is required now are data concerning long-term morbidity and mortality, and whether any practices-including prone positioning, optimal anticoagulation, early extubation and use of mechanical right ventricular support-during ecmo can improve these outcomes. pre-ecmo does the use of a particular combination of immunomodulants (e.g. corticosteroids) ± antiviral agents (e.g. remdesivir) reduce the need for ecmo? should the eolia inclusion criteria be used to decide the timing of ecmo initiation? is there a role for ecpr and how safe is it for the treating teams? are the longer ecmo runs seen in covid- associated with an increase in the risk of ecmo-related complications and morbidity, e.g. nosocomial infection? is there an increase in bleeding or thrombotic complications despite optimal anticoagulation and is this associated with an increase in the risk of mechanical circuit problems or failure? should we screen for dvt/pe during ecmo? are there strategies during ecmo associated with improved long-term outcomes, such as prone positioning; full-dose anticoagulation; awake ecmo (i.e. endotracheal extubation of conscious patients while receiving ecmo); or mechanical right ventricular support during ecmo? if so, what are the mechanisms? is tracheostomy needed in these patients? if yes, what is the optimal timing for the procedure? what are the long-term outcomes of patients with covid- supported with ecmo? should we routinely and systematically screen for dvt/pe after ecmo? what is the maximum duration of ecmo where recovery is still possible and is lung transplantation an option beyond that? covid- : a retrospective cohort study extracorporeal membrane oxygenation for severe acute respiratory distress syndrome how severe covid- infection is changing ards management high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study extracorporeal membrane oxygenation support in covid- : an international cohort study of the extracorporeal life support organization prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: time for a randomized trial prone positioning during venovenous extracorporeal membrane oxygenation in acute respiratory distress syndrome: a multicenter cohort study and propensity-matched analysis extracorporeal membrane oxygenation for patients with covid- in severe respiratory failure integrating the evidence: confronting the covid- elephant provision of ecpr during covid- : evidence, equity, and ethical dilemmas acute heart failure in multisystem inflammatory syndrome in children (mis-c) in the context of global sars-cov- pandemic key: cord- -o isx k authors: ikuyama, yuichi; wada, yosuke; tateishi, kazunari; kitaguchi, yoshiaki; yasuo, masanori; ushiki, atsuhito; urushihata, kazuhisa; yamamoto, hiroshi; kamijo, hiroshi; mita, atsuyoshi; imamura, hiroshi; hanaoka, masayuki title: successful recovery from critical covid- pneumonia with extracorporeal membrane oxygenation: a case report date: - - journal: respir med case rep doi: . /j.rmcr. . sha: doc_id: cord_uid: o isx k a public health emergency of current international concern is the outbreak of a severe respiratory illness, that is, coronavirus disease (covid- ). the disease initially started in wuhan, china, and it rapidly spread to most regions of the world. herein, we report a case of critical covid- pneumonia treated with extracorporeal membrane oxygenation from symptom onset day (sod# ) to sod# . we describe the patient's clinical course, from mild symptoms at the time of illness onset to symptoms of severe pneumonia as the illness progressed. we provide important information regarding our clinical experience for further understanding of management discrepancies, as treatment with extracorporeal membrane oxygenation or pharmacotherapy (e.g., antivirals, immunomodulators, and glucocorticoids) is often dependent on the severity of symptoms. an outbreak of a severe respiratory illness, coronavirus disease (covid- ) , occurred in wuhan, china, in december . the virus that causes covid- , which has rapidly spread to most regions of the world, is called severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] . so far, there are few reports on critical patients with covid- [ , [ ] [ ] [ ] . here, we report the clinical course of a patient with a severe case of covid- complicated with acute respiratory distress syndrome (ards). we report the patient's response to intensive care, including invasive ventilation in the early stage of the illness and extracorporeal membrane oxygenation (ecmo) with antiviral, immunomodulatory, and glucocorticoid therapies as the illness progressed. on february of , a -year-old woman was referred to our hospital in matsumoto, japan, from another hospital in japan, where she was admitted for sore throat, dry cough, and fever that started on february , (symptom onset day ; sod# ). (the term "symptom onset day" is used to illustrate the patient's clinical course, and the term "hospital day" is used to describe treatment measures.) past medical history was significant for diabetes mellitus, hypertension, and glaucoma, but she was otherwise healthy and did not smoke. the patient, an american living in the united states, was visiting japan and arrived at yokohama harbor aboard the diamond princess cruise ship. due to a covid- outbreak inside the cruise ship, she was kept in the cruise ship and underwent viral testing as part of quarantine inspection. a reverse transcription polymerase chain reaction (rt-pcr) test, performed by the japan ministry of health, labour and welfare, produced a positive result for sars-cov- . one day before admission to our hospital, the patient was started on lopinavir-ritonavir ( mg/ mg twice daily orally) and moxifloxacin ( mg once a daily orally). she was transferred to our hospital on sod# (hospital day ;hd# ). on admission, her body temperature was . °c, and her oxygen saturation (spo ) by pulse oximetry was % on l/min of supplemental oxygen via mask. physical examination revealed coarse crackles in the upper chest on the right. laboratory examination revealed peripheral blood lymphopenia ( /μl) and elevated levels of blood urea nitrogen (bun, . mg/dl), creatinine ( . mg/dl), c-reactive protein (crp, . mg/dl), and lactate dehydrogenase (ldh, u/l) ( table ) . chest computed tomography (ct) images showed ground-glass opacities (ggos) and consolidation (figs. a and b). on hd# (sod# ), the patient's respiratory status progressively deteriorated; she exhibited dyspnea despite fever alleviation. the respirator setting at the time was assist/control (volume-controlled ventilation), tidal volume was ml, positive end-expiratory pressure (peep) was cmh o, and respiratory frequency was per minute. her hypoxemia was not improved even if we regulated peep. we considered whether this deterioration might be due to increased airway dead space caused by pulmonary embolism or acute pulmonary edema; however, these diagnoses could not be confirmed with evidence on chest ct scans, which were unobtainable because there was concern about the risk of infecting other patients in the radiology unit. we conducted a compression ultrasound, but were not able to point out deep vein thrombosis. the patient's respiratory status continued to worsen and, despite optimal ventilator settings, we were unable to maintain her pao /fio above torr. therefore, we decided to proceed to venous-venous extracorporeal membrane oxygenation (v-v ecmo) on hd# (sod# ). for v-v ecmo, venous catheters were placed in the right common femoral vein (for drainage) and right internal jugular vein (for infusion). her hemodynamics were maintained using vasoactive agents; we were able to normalize her body water with diuretics and stabilize her oxygenation by ecmo. on hd# (sod# ), to prevent bacterial infection related to catheterization, the previous antibiotics were replaced with vancomycin. her respiratory status gradually improved. on hd# (sod# ), viral testing of an endotracheal aspirate sample showed that sars-cov- was undetectable using rt-pcr. a tracheotomy was performed on hd# (sod# ); ecmo was discontinued on hd# (sod# ). intravenous meropenem was administered for ventilator-associated pneumonia (vap) prophylaxis. chest ct scans obtained on hd# (sod# ) showed enlarged abnormal shadows, ggos, and consolidation in the upper lobe of the right lung, suggesting organizing pneumonia (figs. c and d), which could result in chronic respiratory failure after ecmo cessation. on hd# (sod# ), the patient was started on methylprednisolone mg daily for three days with improvement of her organizing pneumonia on chest x-ray (figs. e and f). on hd# (sod# ), the patient was taken off the respirator, and her condition was stable. we herein report the clinical features of covid- in a critical patient who met the criteria of ards with refractory hypoxemia. in accordance with the first report of covid- from china, the patient initially presented with mild cough and intermittent fever before rapid progression to severe pneumonia that required mechanical ventilation [ ] . detection of sars-cov- rna in a sputum sample on sod# suggests long-term persistence of viral shedding and potential transmissibility (fig. ) . so far, recent studies have described relatively mild cases of covid- in multiple countries [ , , , ] . in a report from the chinese center for disease control and prevention, five percent of patients with covid- were critical and required intensive care [ ] . in critical cases, ards, septic shock, difficulty in correcting metabolic acidosis, and coagulation disorders may develop rapidly [ ] . the current case did not respond to treatment with lopinavir-ritonavir, necessitating ecmo. accumulating evidence strongly indicates that old age and comorbidities like diabetes mellitus and hypertension are risk factors for poor outcome [ , ] , as seen in this patient. in particular, old age increases risk of ards and death associated with covid- [ ] . the laboratory abnormalities in this case (elevated serum crp, ldh, bun, creatinine, and d-dimer levels) coincide with those noted in previous reports [ , ] . the persistent peripheral blood lymphopenia in this case might be indicative of covid- severity, as previous reports have shown lymphopenia to be common in patients with covid- requiring intensive care [ , ] . therefore, it was debated whether ivig therapy should be performed. however, a few reports have shown that the efficacy and adverse effects of ivig therapy are unclear [ , , ] . the present patient was treated with invasive ventilation, which was later switched to ecmo to manage respiratory failure. an overabundance of body fluid may contribute to refractory hypoxemia in patients with ards. in this case, ecmo showed great effectiveness in treating the patient's rapidly deteriorating respiratory status due to pneumonia. the world health organization generally recommends referring patients with refractory hypoxemia to expert centers that are capable of providing ecmo for treatment of severe ards due to covid- [ , ] . recent evidence has suggested that ecmo use in the most severe ards cases was associated with reduced mortality [ ] . in contrast, the potential harm of ecmo in patients with covid- was described by yang et al., who reported death in five of six patients with severe covid- who were treated with ecmo [ ] . risk factors such as advanced age or other complications (e.g., hypertension, diabetes) may be associated with mortality after ecmo induction rather than ecmo induction itself. while the role of ecmo in the management of covid- remains unclear, we suggest that intensive treatment with ecmo offered clinical benefits in the present case. the present case of covid- pneumonia rapidly progressed to ards. the patient's worst respiratory status was observed on hd# (sod# ), as vascular hyperlucency caused pulmonary edema due to uncontrollable inflammation. ecmo was introduced at that time to manage respiratory failure. continued ecmo was tied to successful treatment in this patient. we assumed that intensive management of body fluid levels and proper enteral nutrition in the critical stage of the illness were strongly associated with our successful treatment (fig. ) . the patient's respiratory status was significantly improved until we started administering glucocorticoids for organizing pneumonia on hd# (sod# ). in light of the comorbidities of diabetes mellitus and infectious disease in this patient, glucocorticoids were administered for three days. of note, a recent report suggested that treatment with methylprednisolone in the recovery phase might have been beneficial for patients with covid- who developed ards [ ] . as we experienced in the treatment of this patient, glucocorticoids may be effective for organizing pneumonia due to covid- . in contrast, a study by lansbury et al. demonstrated that glucocorticoids were associated with an increased risk of mortality in patients with influenza [ ] . although glucocorticoids have been widely used in the management of severe acute respiratory syndrome (sars), some studies have demonstrated adverse effects with both short-and long-term administration [ ] [ ] [ ] . no randomized controlled trials have yet resulted in a recommendation for antiviral treatment for patients with suspected or confirmed covid- . management of patients with covid- currently consists of ensuring appropriate infection control and supportive care [ ] . in clinical practice, antiviral agents, including neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, etc.) and ribavirin, in combination with protease inhibitors (like lopinavir-ritonavir) are often used tentatively [ ] . lopinavir-ritonavir has been proposed for the treatment of covid- due to its potential effectiveness in treating sars, as reported in a series of studies [ , ] . moreover, lopinavir has shown an inhibitive effect on middle east respiratory syndrome coronavirus in an in vitro study [ ] . our patient was treated with lopinavir-ritonavir and peramivir, but the clinical benefits did not seem significant. further studies, including randomized controlled trials, are urgently needed to examine the effectiveness of lopinavir-ritonavir in treating covid- [ ] . in summary, we highlight the clinical course of severe covid- in this critical patient and share important clinical information pertaining to our experience, particularly regarding the effective management of acute respiratory failure using ecmo. china novel coronavirus investigating and research team, a novel coronavirus from patients with pneumonia in china china medical treatment expert group for covid- , clinical characteristics of coronavirus disease in china clinical features of patients infected with novel coronavirus in characteristics of and 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distress syndrome and posterior probability of mortality benefit in a post hoc bayesian analysis of a randomized clinical trial preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease . pneumonia in wuhan, china we thank the patient as well as the nurses and clinical staff who provided intensive care for the patient. we would also like to thank the following members of the first sars-cov and tsuyoshi notake, md, phd. we would like to thank editage (www.editage.com) for english language editing. finally, we would like to thank kenichi nishie, md, phd, and akihiro tsukadaira, md, for their initial treatment of the patient at iida municipal hospital, iida, nagano, japan. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. none. • a critical case of -year-old female with covid- pneumonia.• no significant clinical benefits of lopinavir-ritonavir and peramivir treatment.• the pneumonia rapidly progressed to acute respiratory distress syndrome.• extracorporeal membrane oxygenation from illness day to lead to recovery. ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: key: cord- - a pviol authors: kamilia, chtara; regaieg, kais; baccouch, najeh; chelly, hedi; bahloul, mabrouk; bouaziz, mounir; jendoubi, ali; abbes, ahmed; belhaouane, houda; nasri, oussama; jenzri, layla; ghedira, salma; houissa, mohamed; belkadi, kamal; harti, youness; nsiri, afak; khaleq, khalid; hamoudi, driss; harrar, rachid; thieffry, camille; wallet, frédéric; parmentier-decrucq, erika; favory, raphaël; mathieu, daniel; poissy, julien; lafon, thomas; vignon, philippe; begot, emmanuelle; appert, alexandra; hadj, mathilde; claverie, paul; matt, morgan; barraud, olivier; françois, bruno; jamoussi, amira; jazia, amira ben; marhbène, takoua; lakhdhar, dhouha; khelil, jalila ben; besbes, mohamed; goutay, julien; blazejewski, caroline; joly-durand, isabelle; pirlet, isabelle; weillaert, marie pierre; beague, sebastien; aziz, soufi; hafiane, reda; hattabi, khalid; bouhouri, mohamed aziz; hammoudi, driss; fadil, abdelaziz; harrar, rachid al; zerouali, khalid; medhioub, fatma kaaniche; allela, rania; algia, najla ben; cherif, samar; slaoui, mohamed taoufik; boubia, souhail; hafiani, y.; khaoudi, a.; cherkab, r.; elallam, w.; elkettani, c.; barrou, l.; ridaii, m.; mehdi, rihi el; schimpf, caroline; mizrahi, assaf; pilmis, benoît; le monnier, alban; tiercelet, kelly; cherin, mélanie; bruel, cédric; philippart, francois; bailly, sébastien; lucet, jc; lepape, alain; l’hériteau, françois; aupée, martine; bervas, caroline; boussat, sandrine; berger-carbonne, anne; machut, anaïs; savey, anne; timsit, jean-françois; razazi, keyvan; rosman, jérémy; de prost, nicolas; carteaux, guillaume; jansen, chloe; decousser, jean winoc; brun-buisson, christian; dessap, armand mekontso; m’rad, aymen; ouali, zouhour; barghouth, manel; kouatchet, achille; mahieu, rafael; weiss, emmanuel; schnell, david; zahar, jean-ralph; artiguenave, margaux; sophie, paktoris-papine; espinasse, florence; sayed, faten el; dinh, aurélien; charron, cyril; geri, guillaume; vieillard-baron, antoine; repessé, xavier; kallel, hatem; mayence, claire; houcke, stéphanie; guegueniat, pascal; hommel, didier; dhifaoui, kaouther; hajjej, zied; fatnassi, amira; sellami, walid; labbene, iheb; ferjani, mustapha; dachraoui, fahmi; nakkaa, sabrine; m’ghirbi, abdelwaheb; adhieb, ali; braiek, dhouha ben; hraiech, kmar; ousji, ali; ouanes, islem; zaineb, hammouda; abdallah, saousen ben; ouanes-besbes, lamia; abroug, fekri; klein, simon; miquet, mattéo; thouret, jean-marc; peigne, vincent; daban, jean-louis; boutonnet, mathieu; lenoir, bernard; merhbene, takoua; derreumaux, celine; seguin, thierry; conil, jean-marie; kelway, charlotte; blasco, valery; nafati, cyril; harti, karim; reydellet, laurent; albanese, jacques; aicha, narjess ben; meddeb, khaoula; khedher, ahmed; ayachi, jihene; fraj, nesrine; sma, nesrine; chouchene, imed; boussarsar, mohamed; yedder, soumaya ben; samoud, walid; radhouene, bousselmi; mariem, bousselmi; ammar, asma; cheikh, asma ben; lakhal, hend ben; khelfa, messaouda; hamdaoui, yamina; bouafia, nabiha; trampont, timothée; daix, thomas; legarçon, vincent; karam, henri hani; pichon, nicolas; essafi, fatma; foudhaili, nasreddine; thabet, hafedh; blel, youssef; brahmi, nozha; ezzouine, hanane; kerrous, mahmoud; haoui, saad el; ahdil, soufiane; benslama, abdellatif; abidi, khalid; dendane, tarek; oussama, ssouni; belayachi, jihane; madani, naoufal; abouqal, redouane; zeggwagh, amine ali; ghadhoune, hatem; chaari, anis; jihene, guissouma; allouche, hend; trabelsi, insaf; brahmi, habib; samet, mohamed; ghord, hatem el; habiba, ben sik ali; hajer, nouira; tilouch, najla; yaakoubi, sondes; jaoued, oussama; gharbi, rim; hassen, mohamed fekih; elatrous, souheil; arcizet, julien; leroy, bertrand; abdulmalack, caroline; renzullo, catherine; hamet, maël; doise, jean-marc; coutet, jérôme; cheikh, chaigar mohammed; quechar, zakaria; joris, magalie; beauport, dimitri titeca; kontar, loay; lebon, delphine; gruson, bérengère; slama, michel; marolleau, jean-pierre; maizel, julien; gorham, julie; ameye, lieveke; berghmans, thierry; paesmans, marianne; sculier, jean-paul; meert, anne-pascale; guillot, max; ledoux, marie-pierre; braun, thierry; maestraggi, quentin; michard, baptiste; castelain, vincent; herbrecht, raoul; schneider, francis; couffin, severine; lobo, david; mongardon, nicolas; dhonneur, gilles; mounier, roman; le borgne, pierrick; couraud, sophie; herbrecht, jean-etienne; boivin, alexandra; lefebvre, françois; bilbault, pascal; zelmat, setti-aouicha; batouche, djamila-djahida; mazour, fatima; chaffi, belkacem; benatta, nadia; sik, ali habiba; talik, i.; perrier, maxime; gouteix, eliane; koubi, claude; escavy, annabelle; guilbaut, victoria; fosse, jean-philippe; jazia, rahma ben; abdelghani, ahmed; cungi, pierre-julien; bordes, julien; nguyen, cédric; pierrou, candice; cruc, maximilien; benois, alain; duprez, frédéric; bonus, thierry; cuvelier, grégory; ollieuz, sandra; machayekhi, sharam; paciorkowski, frédéric; reychler, gregory; coudroy, remi; thille, arnaud w.; drouot, xavier; diaz, véronique; meurice, jean-claude; robert, rené; turki, olfa; ben, hmida chokri; assefi, mona; deransy, romain; brisson, hélène; monsel, antoine; conti, filomena; scatton, olivier; langeron, olivier; ghezala, hassen ben; snouda, salah; ben, chiekh imen; kaddour, moez; armel, anwar; youness, lafrikh; abdelhak, bensaid; youssef, miloudi; najib, al harrar; mustapha, amouzoun; noufel, mtioui; mohamed, zamd; salma, el khayat; ghizlane, medkouri; mohamed, benghanam; benyounes, ramdani; montini, florent; moschietto, sébastien; gregoire, emilien; claisse, guillaume; guiot, julien; morimont, philippe; krzesinski, jean-marie; mariat, christophe; lambermont, bernard; cavalier, etienne; delanaye, pierre; benbernou, soumia; ilies, sofiane; azza, abdelkader; bouyacoub, khalida; louail, meriem; mokhtari-djebli, houria; arrestier, romain; daviaud, fabrice; francois, xavier laborne; brocas, elsa; choukroun, gérald; peñuelas, oscar; lorente, josé-angel; cardinal-fernandez, pablo; rodriguez, josé-maria; aramburu, josé-antonio; esteban, andres; frutos-vivar, fernando; bitker, laurent; costes, nicolas; le bars, didier; lavenne, franck; devouassoux, mojgan; richard, jean-christophe; mechati, malika; gainnier, marc; papazian, laurent; guervilly, christophe; garnero, aude; arnal, jean michel; roze, hadrien; richard, jean christophe; repusseau, benjamin; dewitte, antoine; joannes-boyau, olivier; ouattara, alexandre; harbouze, nadia; amine, a. m.; olandzobo, a. g.; herbland, alexandre; richard, marie; girard, nicolas; lambron, lucile; lesieur, olivier; wainschtein, sarah; hubert, sidonie; hugues, albane; tran, marc; bouillard, philippe; loteanu, vlad; leloup, maxime; laurent, alexandra; lheureux, florent; prestifilippo, alessia; cruz, martin delgado maria; romain, rigal; antonelli, massimo; blanch, torra lluis; bonnetain, franck; grazzia-bocci, maria; mancebo, jordi; samain, emmanuel; paul, hebert; capellier, gilles; zavgorodniaia, taissa; soichot, marion; malissin, isabelle; voicu, sebastian; garçon, pierre; goury, antoine; kerdjana, lamia; deye, nicolas; bourgogne, emmanuel; megarbane, bruno; mejri, olfa; hmida, marwa ben; tannous, salma; chevillard, lucie; labat, laurence; risede, patricia; fredj, hana; léger, maxime; brunet, marion; le roux, gaël; boels, david; lerolle, nicolas; farah, souaad; amiel-niemann, hélène; kubis, nathalie; declèves, xavier; peyraux, nicoals; baud, frederic; serafini, micaela; alvarez, jean-claude; heinzelman, annette; jozwiak, mathieu; millasseau, sandrine; teboul, jean-louis; alphonsine, jean-emmanuel; depret, françois; richard, nathalie; attal, pierre; richard, christian; monnet, xavier; chemla, denis; jerbi, salma; khedhiri, wafa; necib, hatem; scarfo, paolo; chevalier, charles; piagnerelli, michael; lafont, alexandre; galy, antoine; mancia, claire; zerhouni, amel; tabeliouna, kheira; gaja, ali; hamrouni, bassem; malouch, abir; fourati, sami; messaoud, rihab; zarrouki, youssef; ziadi, amra; rhezali, manal; zouizra, zahira; boumzebra, drissi; samkaoui, mohamed abdennasser; brunet, jennifer; canoville, bertrand; verrier, pierre; ivascau, calin; seguin, amélie; valette, xavier; du cheyron, damien; daubin, cedric; bougouin, wulfran; aissaoui, nadia; lamhaut, lionel; jost, daniel; maupain, carole; beganton, frankie; bouglé, adrien; dumas, florence; marijon, eloi; jouven, xavier; cariou, alain; poirson, florent; chaput, ulriikka; beeken, thomas; maxime, leclerc; haikel, oueslati; vodovar, dominique; chelly, jonathan; marteau, philippe; chocron, richard; juvin, philippe; loeb, thomas; adnet, frederic; lecarpentier, eric; riviere, antoine; de cagny, bertand; soupison, thierry; privat, elodie; escutnaire, joséphine; dumont, cyrielle; baert, valentine; vilhelm, christian; hubert, hervé; leteurtre, stéphane; fresco, marion; bubenheim, michael; beduneau, gaetan; carpentier, dorothée; grange, steven; artaud-macari, elise; misset, benoit; tamion, fabienne; girault, christophe; dumas, guillaume; chevret, sylvie; lemiale, virginie; mokart, djamel; mayaux, julien; pène, frédéric; nyunga, martine; perez, pierre; moreau, anne-sophie; bruneel, fabrice; vincent, françois; klouche, kada; reignier, jean; rabbat, antoine; azoulay, elie; frat, jean-pierre; ragot, stéphanie; constantin, jean-michel; prat, gwenael; mercat, alain; boulain, thierry; demoule, alexandre; devaquet, jérôme; nseir, saad; charpentier, julien; argaud, laurent; beuret, pascal; ricard, jean-damien; teiten, christelle; marjanovic, nicolas; palamin, nicola; l’her, erwan; bailly, arthur; boisramé-helms, julie; champigneulle, benoit; kamel, toufik; mercier, emmanuelle; le thuaut, aurélie; lascarrou, jean-baptiste; rolle, amélie; de jong, audrey; chanques, gérald; jaber, samir; hariri, geoffroy; baudel, jean-luc; dubée, vincent; preda, gabriel; bourcier, simon; joffre, jeremie; bigé, naïke; ait-oufella, hafid; maury, eric; mater, houda; merdji, hamid; grimaldi, david; rousseau, christophe; mira, jean-paul; chiche, jean-daniel; sedghiani, ines; benabderrahim, a.; hamdi, dhekra; jendoubi, asma; cherif, mohamed ali; hechmi, youssef zied el; zouheir, jerbi; bagate, françois; bousselmi, radhwen; schortgen, frédérique; asfar, pierre; guérot, emmanuel; fabien, grelon; anguel, nadia; sigismond, lasocki; matthieu, henry-lagarrigue; gonzalez, frédéric; françois, legay; guitton, christophe; schenck, maleka; jean-marc, doise; dreyfuss, didier; radermacher, peter; frère, antoine; martin-lefèvre, laurent; colin, gwenhaël; fiancette, maud; henry-laguarrigue, matthieu; lacherade, jean-claude; lebert, christine; vinatier, isabelle; yehia, aihem; joret, aurélie; menunier-beillard, nicolas; benzekri-lefevre, dalila; desachy, arnaud; bellec, fréderic; plantefève, gaëtan; quenot, jean-pierre; meziani, ferhat; tavernier, elsa; ehrmann, stephan; chudeau, nicolas; raveau, tommy; moal, valérie; houillier, pascal; rouve, emmanuelle; lakhal, karim; gandonnière, charlotte salmon; jouan, youenn; bodet-contentin, laetitia; balmier, adrien; messika, jonathan; de montmollin, etienne; pouyet, victorine; sztrymf, benjamin; thiagarajah, abirami; roux, damien; de chambrun, marc pineton; luyt, charles-edouard; beloncle, françois; zapella, nathalie; ledochowsky, stanislas; terzi, nicolas; mazou, jean-marc; sonneville, romain; paulus, sylvie; fedun, yannick; landais, mickael; raphalen, jean-herlé; combes, alain; amoura, zahir; jacquemin, aemilia; guerrero, felipe; marcheix, bertrand; hernandez, nicolas; fourcade, olivier; georges, bernard; delmas, clément; makoudi, sarah; genton, audrey; bernard, rémy; lebreton, guillaume; amour, julien; mazet, charlotte; bounes, fanny; murat, gurbuz; cronier, laure; robin, guillaume; biendel, caroline; silva, stein; boubeche, samia; abriou, caroline; wurtz, véronique; scherrer, vincent; rey, nathalie; gastaldi, gioia; veber, benoit; doguet, fabien; gay, arnaud; dureuil, bertrand; besnier, emmanuel; rouget, antoine; gantois, guillaume; magalhaes, eric; wanono, ruben; smonig, roland; lermuzeaux, mathilde; lebut, jordane; olivier, andremont; dupuis, claire; radjou, aguila; mourvillier, bruno; neuville, mathilde; d’ortho, marie pia; bouadma, lila; rouvel-tallec, anny; rudler, marika; weiss, nicolas; perlbarg, vincent; galanaud, damien; thabut, dominique; rachdi, emna; mhamdi, ghada; trifi, ahlem; abdelmalek, rim; abdellatif, sami; daly, foued; nasri, rochdi; tiouiri, hanene; lakhal, salah ben; rousseau, geoffroy; asmolov, romain; grammatico-guillon, leslie; auvet, adrien; laribi, said; garot, denis; dequin, pierre françois; guillon, antoine; fergé, jean-louis; abgrall, gwénolé; hinault, ronan; vally, shazima; roze, benoit; chaplain, agathe; chabartier, cyrille; savidan, anne-charlotte; marie, sabia; cabie, andre; resiere, dabor; valentino, ruddy; mehdaoui, hossein; benarous, lucas; soda-diop, marième; bouzana, fouad; perrin, gilles; bourenne, jeremy; eon, béatrice; lambert, dominique; trebuchon, agnes; poncelet, géraldine; le bourgeois, fleur; michael, levy; camille, guillot; naudin, jérôme; deho, anna; dauger, stéphane; sauthier, michaël; bergeron-gallant, krystale; emeriaud, guillaume; jouvet, philippe; tiebergien, nicolas; jacquet-lagrèze, matthias; fellahi, jean-luc; baudin, florent; essouri, sandrine; javouhey, etienne; guérin, claude; lampin, marie; mamouri, ouardia; devos, patrick; karaca-altintas, yasemin; vinchon, matthieu; brossier, david; eltaani, redha; teyssedre, sonia; sabine, meyet; bouchut, jean-christophe; peguet, olivier; petitdemange, lucie; guilbert, anne sophie; aoul, nabil tabet; addou, zakaria; aouffen, nabil; anas, benqqa; kalouch, samira; yaqini, khalid; chlilek, aziz; abdou, rchi; gravellier, perrine; chantreuil, julie; travers, nadine; listrat, antoine; le reun, claire; favrais, geraldine; coppere, zoe; blanot, stéphane; montmayeur, juliette; bronchard, régis; rolando, stephane; orliaguet, gilles; leger, pierre-louis; rambaud, jérôme; thueux, emilie; de larrard, alexandra; berthelot, véronique; denot, julien; reymond, marie; amblard, alain; morin-zorman, sarah; lengliné, etienne; pichereau, claire; mariotte, eric; emmanuel, canet; poujade, julien; trumpff, guillaume; janssen-langenstein, ralf; harlay, marie-line; zaid, noorah; ait-ammar, nawel; bonnal, christine; merle, jean-claude; botterel, francoise; levesque, eric; riad, zakaria; mezidi, mehdi; yonis, hodane; aublanc, mylène; perinel-ragey, sophie; lissonde, floriane; louf-durier, aurore; tapponnier, romain; louis, bruno; forel, jean-marie; bisbal, magali; lehingue, samuel; rambaud, romain; adda, mélanie; hraiech, sami; marchi, elisa; roch, antoine; guerin, vincent; rozencwajg, sacha; schmidt, matthieu; hekimian, guillaume; bréchot, nicolas; trouillet, jean louis; besset, sébastien; franchineau, guillaume; nieszkowska, ania; pascal, leprince; loiselle, maud; sarah, chemam; laurence, dangers; guillemette, thomas; jacquens, alice; kerever, sebastien; guidet, bertrand; aegerter, philippe; das, vincent; fartoukh, muriel; hayon, jan; desmard, mathieu; fulgencio, jean-pierre; zuber, benjamin; soufi, a.; khaleq, k.; hamoudi, d.; garret, charlotte; peron, matthieu; coron, emmanuel; bretonnière, cédric; audureau, etienne; audrey, winters; christophe, duvoux; christian, jacquelinet; daniel, azoulay; cyrille, feray; aissaoui, wissal; rghioui, kawtar; haddad, wafae; barrou, houcine; carteaux-taeib, anna; lupinacci, renato; manceau, gilles; jeune, florence; tresallet, christophe; habacha, sahar; fathallah, ines; zoubli, aymen; aloui, rafaa; kouraichi, nadia; jouet, emilie; badin, julie; fermier, brice; feller, marc; serie, mathieu; pillot, jérôme; marie, william; gisbert-mora, chloé; vinclair, camille; lesbordes, pierre; mathieu, pascal; de brabant, fabienne; muller, emmanuel; robaux, marie-aline; giabicani, mikhael; marchalot, antoine; gelinotte, stéphanie; declercq, pierre louis; eraldi, jean-pierre; bougerol, françois; meunier-beillard, nicolas; devilliers, hervé; rigaud, jean-philippe; verrière, camille; ardisson, fanny; kentish-barnes, nancy; jacq, gwenaëlle; chermak, akli; lautrette, alexandre; legrand, matthieu; soummer, alexis; thiery, guillaume; cottereau, alice; canet, emmanuel; caujolle, marie; allyn, jérôme; valance, dorothée; brulliard, caroline; martinet, olivier; jabot, julien; gallas, thomas; vandroux, david; allou, nicolas; durand, arthur; nevière, rémi; delguste, florian; boulanger, eric; preau, sebastien; martin, ruste; cochet, hélène; ponthus, jean pierre; amilien, virginie; tchir, martial; barsam, elise; ayoub, mohsen; georger, jean francois; guillame, izaute; assaraf, julie; tripon, simona; mallet, maxime; barbara, guilaume; louis, guillaume; gaudry, stéphane; barbarot, nicolas; jamet, angéline; outin, hervé; gibot, sébastien; bollaert, pierre-edouard; holleville, mathilde; legriel, stéphane; chateauneuf, anne laure; cavelot, sébastien; moyer, jean-denis; bedos, jean pierre; merle, philippe; laine, aurelie; natalie, de sa; cornuault, mathieu; libot, jérome; asehnoune, karim; rozec, bertrand; dantal, jacques; videcoq, michel; degroote, thècle; jaillette, emmanuelle; zerimech, farid; malika, balduyck; llitjos, jean-françois; amara, marlène; lacave, guillaume; pangon, béatrice; mavinga, josé; makunza, joseph nsiala; mafuta, m. e.; yanga, yves; eric, amisi; ilunga, jp; kilembe, ma; alby-laurent, fanny; toubiana, julie; mokline, amel; laajili, achraf; amri, helmi; rahmani, imene; mensi, nidhal; gharsallah, lazheri; tlaili, sofiene; gasri, bahija; hammouda, rym; messadi, amen allah; allain, pierre-antoine; gault, nathallie; paugam-burtz, catherine; foucrier, arnaud; chatbri, bassem; bourbiaa, yousra; thabet, lamia; neuschwander, arthur; vincent, looten; beck, jennifer; vibol, chhor; amelie, yavchitz; resche-rigon, matthieu; pirracchio, jean mantzromain; bureau, côme; decavèle, maxens; campion, sébastien; ainsouya, roukia; niérat, marie-cécile; prodanovic, hélène; raux, mathieu; similowski, thomas; dubé, bruno-pierre; demiri, suela; dres, martin; may, faten; quintard, hervé; kounis, ilias; saliba, faouzi; andré, stephane; boudon, marc; ichai, philippe; younes, aline; nakad, lionel; coilly, audrey; antonini, teresa; sobesky, rodolphe; de martin, eleonora; samuel, didier; hubert, noemie; nay, mai-anh; auchabie, johann; giraudeau, bruno; jean, reignier; darmon, michaël; ruckly, stephane; garrouste-orgeas, maïté; gratia, elisabeth; goldgran-toledano, dany; jamali, samir; dumenil, anne sylvie; schwebel, carole; brisard, laurent; bizouarn, philippe; lepoivre, thierry; nicolet, johanna; rigal, jean christophe; roussel, jean christian; cheurfa, cherifa; abily, julien; lescot, thomas; page, isaline; warnier, stéphanie; nys, monique; rousseau, anne-françoise; damas, pierre; uhel, fabrice; lesouhaitier, mathieu; grégoire, murielle; gaudriot, baptiste; gacouin, arnaud; le tulzo, yves; flecher, erwan; tarte, karin; tadié, jean-marc; georges, quentin; soares, m.; jeon, kyeongman; oeyen, sandra; rhee, chin kook; gruber, pascale; ostermann, marlies; hill, quentin; depuydt, peter; ferra, christelle; muller, alice; aurelie, bourmaud; niles, christopher; herbert, fabien; pied, sylviane; loridant, séverine; françois, nadine; bignon, anne; sendid, boualem; lemaitre, caroline; dupre, celine; zayene, aymen; portier, lucie; de freitas caires, nathalie; lassalle, philippe; le neindre, aymeric; selot, pascal; ferreiro, daniel; bonarek, maria; henriot, stépahen; rodriguez, julie; taddei, mara; di bari, mauro; hickmann, cheryl; castanares-zapatero, diego; deldicque, louise; van den bergh, peter; caty, gilles; roeseler, jean; francaux, marc; laterre, pierre-françois; dupuis, bastien; machayeckhi, sharam; sarfati, celine; moore, alex; mendialdua, paula; rodet, emilie; pilorge, catherine; stephan, francois; rezaiguia-delclaux, saida; dugernier, jonathan; hesse, michel; jumetz, thibaud; bialais, emilie; depoortere, virginie; michotte, jean bernard; wittebole, xavier; jamar, françois title: proceedings of réanimation , the french intensive care society international congress date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: a pviol nan introduction the study of the bacterial cartography in thoracic surgery is extremely important for the treatment of post-operative infections due to the severity of the underlying pathology, the fragility of patients after surgery in addition to the choice of the empiric antibiotic therapy. we led a prospective study following all the patients who underwent a pulmonary resection surgery for a period of months from january to july , jointly with the microbiology department, chu ibn rochd, casablanca. the bronchial secretions were collected by a protected distal bronchial sample using a (combicath) after the intubation. results during the period of the study, patients underwent a pulmonary resection, % for a neoplastic pathology. the medium age was years ± and % of our sample were male. % of our patients had smoking habits and of them had pulmonary tuberculosis, had repeated respiratory infections. the antibiotics used in pre-operative: % of beta-lactams; % of fluoroquinolones; % of macrolides. moreover, % of our patients were classified asa . of the obtained samples, were positive ( . %). the most frequently observed germs were the acinetobacter baumannii ( . %), pseudomonas aeruginosa ( . %), klebsiella pneumoniae ( . %), staphylococcus aureus ( . %). the acinetobacter baumannii was the most resistant germ ( % sensibility to carbapenem). these patients were followed until their d after surgery, of them developed a post-operative pneumonitis with cases of multi-resistant acinetobacter baumanii, of which deceased. conclusion pneumonitis after pulmonary resection are common and severe that's why it is necessary to establish a global prevention strategy mainly based on general patricians and pneumologists' awareness concerning the choice of the prescribed antibiotics, in order to avoid the spread of multi-resistant germs. introduction carbapenemase-producing enterobacteriaceae (cpec) are increasingly reported worldwide and constitutes a real challenge antibiotic for clinicians to preserve the bacterial ecology. its incidence has remarkably increased in our intensive care unit during the last years. the esbl spread has a major consequence in term of antibiotic choices. carbapenem antibiotic are regarded as the most effective treatment. however numbers of authors suggest that alternatives antibiotics (i.e. noncarbapenems) could be used in esbl-pe infections. there are some conflicting data regarding the use of alternatives in case of esbl-pe infections. moreover as far as we know, there are no data in icu. objectives the aim of this study was to describe esbl-pe infections in icu and therapeutic options chosen in these specific situations. patients and methods prospective multicentric observational cohort study conducted in volunteers icu. all consecutive patients hospitalized in icu with esbl-pe infection according to cdc definitions were included. severity of illness was defines according to bone criteria, saps ii and sofa. demographic datas, empirical and definitive antibiotic therapy (et and dt), clinical evolution, and outcome were recorded. in vitro antimicrobial susceptibility testing was performed by the disk diffusion method or the vitek system according to the guidelines of the antibiogram committee of the french microbiologic society. results during the study period patients with esbl-pe infection met eligibility criteria with respectively a median age and saps ii score of ( - ) and ( - ). the median sofa score at first day of antibiotic therapy and icu admission were ( - ) and ( ) ( ) ( ) ( ) ( ) ( ) ( ) respectively. the most frequent site of infection were respiratory tract ( %), urinary tract ( %) and abdominal ( %). the most frequent isolated species were: escherichia coli ( %), klebsiella sp ( %) and enterobacter sp ( %). respectively , and % patients had septic shock, severe sepsis and sepsis according to bone criteria. among esbl-pe, . % were carbapenem and . were blbi sensitive. among the whole population, ( %) patients received a carbapenems as et. ( %) received a dt with carbapenems and ( %) patients received an alternative dt. the most frequent reasons for maintaining carbapenems as dt were: antibiotic susceptibility tests ( % of cases), severity level ( % of cases) immunosuppression ( % of cases). the median length of icu stay after infection was respectively ( - ) and ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days for carbapenems and alternatives dt (p = . ). the d mortality was % for patients with carbapenems dt and % for patients with alternatives dt (p = . ). surprisingly, there were no differences between the groups (carbapenems vs alternatives) in term of severity. conclusion alternatives are frequently used for esbl-pe infections in icu. in our cohort ( %) patients received antibiotics other than carbapenems regardless of the severity. introduction bacterial resistance to antibiotics is a common problem worldwide. in south america, this prevalence is reported to be the highest in the world. however, in french guyana, there is no data on the epidemiology of colonization and infection caused by extended spectrum b-lactamase producing enterobacteriaceae (esbl-pe). we conducted this study to investigate the prevalence of colonization with esbl-pe and subsequent icu acquired infection in french guiana. introduction the implementation of hemofiltration (hf) as a renal replacement therapy in septic shock patients requires the supply of large quantities of replacement solutions. these solutions are either industrially prepared in autoclaved expensive plastic bags (conventional hemofiltration, chf) or continuously provided in unlimited amounts at the dialysis machine directly from the water treatment plant to form the replacing solutions (on-line hemofiltration, olhf).the aim of our study was to evaluate the safety and effectiveness of on-line hemofiltration compared to conventional hemofiltration in septic shock patients. the investigative protocol was approved by the institutional ethics authorities and all patients or their legally authorized representatives provided written informed consent. it was a prospective, randomized, clinical study, including septic shock patients with acute renal failure. patients were randomized to receive either on-line hemofiltration (n = ) or conventional hemofiltration (n = ) for renal replacement therapy during days. hemodynamic monitoring was conducted by conventional devises, including: electrocardiogram and a radial arterial catheter for invasive arterial pressure every h during period study. we collected serum samples also every h (urea, potassium and sodium levels, troponin, hemoglobin, platelets, c-reactive protein and lactates). results the evolution of heart rate (hr), mean arterial pressure (map), biological markers were comparable between the two groups over time except a significant decrease in map in the olhf group compared to chf group only at h (p = . ) and h (p = . ) and a significant decrease in c-reactive protein level in the olhf group at h (p = . ). conclusion on-line hemofiltration seems to be a safe and reliable method of renal replacement therapy in septic shock patients. it may be associated with attenuated pro-inflammatory cytokine profile (c-reactive protein). none. introduction therapeutic plasma exchange (tpe) is crucial for the management of auto-immune diseases like thrombotic thrombocytopenic purpura or myasthenia gravis. tpe is performed either by centrifugation, with specific machines which are not routinely available in icus, or by using specific plasma separation membranes with widely spread in icus hemofiltration machines. regional citrate anticoagulation for tpe is well established with centrifugation but has been seldom described for membrane tpe. we are reporting the experience of our icu in this field. patients and methods retrospective study including all patients who received tpe with citrate regional anticoagulation between and in an -bed icu. tpe is performed solely in the icu in our institution. results patients were included. tpe was required for thrombotic microangiopathy ( patients), vasculitis ( patients), hyperviscosity syndrome ( patients), guillain-barré syndrome ( cases) and others ( patients) . mean saps score was [standard deviation (sd) . ] . tpe were performed, with a mean number of . (sd . ; range - ) tpe per patients. coagulation of the circuit of tpe occurred in ( %) patients. coagulation of the circuit occurred in . % ( / ) of the tpe. minor adverse events have been reported in two patients: one had a rash during the first tpe (no recurrence during the next tpes) and the other had paresthesia during the first two tpes (the calcium infusion was increased and there had been no recurrence during the next tpes). no serious adverse events related to citrate were observed. conclusion regional anticoagulation with citrate allowed us to perform tpe in patients, without significant adverse events. the rate of circuit coagulation was . % per tpe. none. introduction a reduced incidence of membrane thrombosis after injection of anti-thrombin (at) has been reported in septic patients with acquired deficit in at undergoing continuous hemofiltration. as this strategy was routinely performed in our unit until , we investigated its cost-effectiveness. patients and methods data about the use of hemofiltration, the consumption of at and hemofiltration devices during (period with routine use of at) and (period with use of at only if a membrane thrombosis occurred) were extracted from the administrative database of the institution. a decisional tree was built to modelize the impact of at on the consumption of hemofiltration devices and blood products. the decisional tree took into account the probability of membrane thrombosis with and without at and the probability of transfusion after membrane thrombosis. costs were obtained from the pharmacy of the institution (at, hemofiltration devices) and from the literature (blood products). results during , days of hemofiltration were performed, with the use of doses of at ( , €) and hemofiltration devices ( , €) . during , (− %) days of hemofiltration were performed, with the use of (− %) doses of at ( €) and (+ %) hemofiltration devices ( , €) . the mean cost of day of hemofiltration decreased from € to € with the diminution of the use of at. according to the decisional tree, at was almost never cost-effective. the only circumstances associated with a benefit for the use of at was the association of a probability of thrombosis with at inferior to . , of a probability of thrombosis without at equal , of a probability of transfusion after thrombosis equal and a cost of transfusion of €. in these extremely favorable circumstances, at could decrease the daily cost of hemofiltration of . - . €. discussion the model has several limits: the losses of utility related to transfusion and to interruption of hemofiltration due to thrombosis were not taken into account; the cost of at measurement was not estimated; the work load of changing a membrane and of transfusion after membrane thrombosis was not analyzed. conclusion our results suggest that anti-thrombin is not costeffective to reduce the costs of hemofiltration related to membrane thrombosis. none. introduction in intensive care unit (icu), some patients suffering from acute kidney injury need renal replacement therapy (rrt). it requires the circuit anticoagulation, this could be done by a regional citrate method. today, this is a recommended approach for the everyday care, even if the technique isn't widespread yet [ ] . the ionized calcemia dosing through the filter ("post-filter" ionized-calcemia) is used to monitor the technique efficacy, with a target of . - . mmol/l showing a good filter anticoagulation. the objective of our study was the assessment of efficacy and safety of our regional citrate anticoagulation protocol, with a less restrictive post-filter ionized calcemia target ( . - . mmol/l). the main goal was the analysis of the circuit lifespan, considering a lifespan above h, as well as the search of some clinical and biological factors affecting the technique efficacy. moreover, we analyzed the side effects incidence of the protocol (hypernatremia, metabolic alcalosis), and their consequences. the study received the scientific ethical agreement of university hospital of toulouse, and is registered with number - . patients and methods patients, admitted to one of the two university hospital icus of toulouse, needing a continuous rrt method, without any need for systemic heparin anticoagulation, and without severe hepatocellular failure, were included in the study. filters included over a -year period were analyzed. results results show a mean filter lifespan of h, with a lifespan above h for . % of all filters. coagulation was the cessation reason for . % of filters, most of them before h of the filter use. a value of post-filter ionized calcemia at day below . mmol/l was the main factor influencing a filter lifespan above h. an age older than and a saps ii severity score below were other factors conditioning a filter lifespan of more than h. side effects of citrate were rare and didn't have any clinical impact among our patients. discussion these results suggest that citrate used for anticoagulation in rrt could have an additional anti inflammatory effect through the induced hypocalcemia, as well as an energetic gain which could lead to a renal protection against ischemia-reperfusion mechanism [ ] . moreover, these results call into question the need of post-filter ionized calcemia dosing for the monitoring of citrate anticoagulation efficacy, since the method safety is monitored by the total-to-ionized calcium ratio. conclusion during continuous rrt in icu, a regional citrate anticoagulation protocol with a non-restrictive post-filter ionized calcemia target seems to be efficient and could reduce side effects. these results need to be confirmed with a randomised control study. introduction continuous veno-venous haemofiltration (cvvh) is used to treat acute kidney injury in critically ill patients. to optimize its efficiency, cvvh requires effective anticoagulation. systemic anticoagulation with standard heparin, the most used, can lead to major bleeding complications. hemofilters that are able to adsorb heparin molecules on their surface such as an st and oxiris membranes represent an alternative. the objective of this study was to compare these two types of filters in terms of duration, efficiency, dysfunctions and cost. materials and methods from october to may , we conducted a retrospective, observational, and non-interventional study. all patients admitted in the intensive care unit needing cvvh were included. the primary endpoint was the filter lifespan: an st versus oxiris. the secondary endpoint was the filter efficiency (urea reduction ratio: urr). the main analysis did not consider the anticoagulation type. we conducted a subgroup analysis taking into account the use or not of an anticoagulation. results sessions in patients were carried out using filters representing , h of treatment. the mean an st filter lifespan was ± h and ± h for oxiris filters (p > . ). there is no significant difference in terms of duration between the two filters. the subgroup analysis taking into consideration the use or not of anticoagulation did not show any difference either. the mean urr was ± % in the an st group and ± % in the oxiris group (p > . ). concerning the dysfunctions, there were no significant difference between the two filters. one hundred and seventy-six an st filters were used for a total cost of , euros. two hundred and ten oxiris filters were used for a total cost of , euros. conclusion the an st and oxiris lifespans are not significantly different. they were as efficient in terms of blood epuration and had as many dysfunctions. the use of an oxiris filter rather than an an st to extend the circuit's lifespan in the same clinical conditions is not justified considering the extra cost generated. introduction because oliguria is a poor prognostic sign in patients with acute renal failure (arf), diuretics are often used to increase urine output in patients with or at risk of arf. from a pathophysiological point of view there are several reasons to expect that loop diuretics could have a beneficial effect on renal function. however, a review of literature shows that the use of loop diuretics in patients with arf has been associated with inconclusive results despite the theoretical benefits [ ] . to assess the adjunctive effect of diuretics, to alter the progression to kidney injury or failure, in patients at risk for acute renal failure. patients and methods this is a retrospective chart review of consecutive patients who developed arf with oliguria in the intensive care unit. chart abstractors were well trained residents. two chart reviewers (senior intensivists) studied all the charts. an explicit protocol was used to precise all needed definitions. uniform handling of data was ensured especially for conflicting, missing or unknown data. oliguria was defined as urine output lower than . ml/kg/h for at least h. rifle score was assessed before and after urinary output normalisation. therapeutic intervention to optimize pre-renal perfusion was described. mean arterial blood pressure (mbp) before and after therapeutic initiation, oliguria duration, delay from oliguria onset to diuretic administration, delay from diuretic administration to urinary output normalisation were measured. results patients were studied over a years period. ] h. the delay from diuretic administration to urinary output normalization was [ . , ] h. after resumption of diuresis, rifle score was assessed as (patients without risk, %; r, %; i, %; f, % l, zero; e, zero) (fig. ) . increased serum creatinine level, above . fold normal range, was observed only in ( %) patients. conclusion rapid optimization of pre-renal hemodynamic disturbances associated with short delay administration of diuretics could significantly alter the progression to kidney injury or failure in at risk acute renal failure icu patients. the ventilator associated pneumonia (vap) is a common and severe complication of assisted ventilation. it's the leading cause of nosocomial infections in intensive care unit and remain responsible for a high morbidity and mortality because of the emergence of multidrug resistant (mdr) bacterial agent such us acinetobacter baumannii (ab). the aim of this study was to determine the incidence, risk factors and prognosis of ab vap. patients and methods retrospective study extending over a year period (january -january ) that included all patients over patients were divided into two groups: one consisting of patients who developed vap to ab and the second developed vap to another bacterial pathogen. results one hundred and forty patients developed vap. the incidence rate of ab vap was . % with a density of incidence of . per ventilator days. age, male gender, the time between hospitalization and mechanical ventilation and the medical pathology were risk factors for developing ab vap. ab was resistant to ceftazidime in %, to imipenem in %, tobramycin in % and netilmycin in . %, rifampin in % with a sensitivity to colistin in % of cases. the resistance of this germ to imipenem increased from % in to . % in . the evolution of patients with ab vap developed frequently septic shock compared to other patients ( vs . %; p = . ). the ab vap mortality was higher ( vs %; p = . ). conclusion the increasing incidence of multi-drug resistant ab vap is responsible for a high morbidity and mortality. so we need to identify risk factors and to strengthen the means of prevention of hand contamination and cross transmission during invasive procedures. introduction central line associated bloodstream infections (clabsi) are among the serious hospital-acquired infections. the aim of this study is to determine the incidence of clabsi, the pathogens and the risk factors that play a role in the development of bsi among patients followed in a tunisian medical intensive care unit. patients and methods all patients admitted for more than h were included in the study over a -year period in an -bed medical icu. the enrollment was based on clinical and laboratory diagnosis of bsi. blood samples were collected from catheter hub of all patients for culture, followed by identification and antibiotic sensitivity testing of the isolates. was higher compared with the mean rate of clabsi in icu reported by the nnis system surveillance for , which is . / catheter.days [ ] . duration of catheterization, frequent manipulation of catheter, catheter location, catheter type, underlying diseases, suppression of immune system, and types of fluids administered through the catheter are significant risk factors in development of bsis [ ] . in our study both duration of catheterization and number of attempts are independent factors for clabsi. conclusion in a monocenter cohort, clabsi had a moderate density rate but are associated with poor outcome. identifying the risk factors is necessary to find solutions for this major health problem. introduction according to some studies, field-intubated patients have . - times greater risk of ventilator associated pneumonia (vap). endobronchial intubation (ei) can be unrecognized by the physicians and may result in complications such as atelectasis which in turn could increase the risk of vap. the aim of our study was to confirm this hypothesis. patients and methods this monocentric retrospective study included all consecutive patients > years who underwent an out-of-hospital tracheal intubation before their admission to the intensive care unit (icu) between january and december . exclusion criteria were suspected aspiration or pneumonia on admission, patients who died within the first days of icu stay, extubation in less than h and underlying disease making radiological interpretation difficult for vap diagnosis. vap were divided into early onset (< days) and late onset (≥ days) events and were independently diagnosed by two experienced intensivists who had no access to the initial chest x-ray performed to check the position of the tracheal tube, based on the clinical pulmonary infection score. onset of ventilator associated tracheobronchitis (vat) was also noted. inadvertent endobronchial intubation was determined by another independent physician based on the interpretation of admission chest x-ray. results patients were intubated out-of-hospital. of the patients excluded, had an extubation in less than h, were died within the first days, had a suspicion of pneumonia, a suspicion of aspiration and an underlying disease making radiological interpretation difficult. of the patients included, ( . %) had an ei upon admission. no significant difference was observed between the ei and non-ei group for gender, age, saps , comorbidities and diagnostic category (cardiorespiratory arrest, trauma, coma and cardiorespiratory failure). early-onset vap were diagnosed in % in the ei group and in % of non-ei patients (p = . ). adding early onset vat, the respiratory infection rate was % in the ei group and % in the non-ei group (p = . ) (fig. ). late-onset vap were observed in . % in the non-ei group and . % in the ei group, without difference between groups (p = . ). there was no inter-group difference in the duration of ventilation, duration of icu stay and icu mortality. staphyloccocus aureus was the most prevalent pathogen in patients with early-onset vap ( . %, only one strain was methicillin-resistant). conclusion this study found a high rate of inadvertent prehospital endobronchial intubation with a higher incidence of early-onset vap. these results support the implementation of specific procedures to decrease the incidence of ei. introduction ventilator-associated pneumonia (vap) is associated with increased hospital stay and high morbidity and mortality in critically ill patients. the classic dichotomy between early and late onset vap is no longer helpful available. the aims of this study were to determine the incidence of multidrug-resistant pathogens in the first episodes of vap and to assess potential differences in bacterial profiles of subjects with early-onset versus late-onset vap. patients and methods retrospective cohort study over a period of months including all patients who had a first episode of vap confirmed by positive culture. subjects were distributed into groups according to the number of intubation days: early-onset vap (< days) or late-onset vap (≥ days).the primary endpoint was the nature of causative pathogens and their resistance profiles. results sixty patients were included, men and women. the average age was ± years. the igs at admission was . [ ; ] apache [ ; ] . monomicrobial infections were diagnosed in of patients ( %).two different bacteria were isolated in cases ( %). a. baumannii was the most frequently isolated in % (n = ) of patients; followed by p. aeruginosa in % (n = ), enterobacteriaceae in % (n = ) and s. aureus in % (n = ). the isolated bacteria were multidrug-resistant in most cases ( / ). the vap group comprised episodes ( %) of early-onset vap and episodes ( %) of late-onset vap. a. baumannii was isolated in % of early vap (n = ) versus % of late vap (n = ) (p = ns), p. aeruginosa in % of early vap (n = ) versus % of late vap (n = ) (p = ns) and enterobacteriaceae in % of early vap (n = ) versus % of late vap (n = ) (p = ns). for the resistance profile of the different pathogens isolated, there was no difference between early and late onset vap. conclusion according to new data from the literature, there were no microbiological differences in the prevalence of potential multidrugresistant pathogens or in their resistance profiles associated with early-onset versus late-onset vap. the bacterial nosocomial infection is a major cause of morbidity and mortality in burned. the bacterial ecology in an icu has a major impact in terms of morbidity and mortality, particularly in the center of burned or length of stay of patients is increased compared to a general intensive care. we conducted an observational study spread over months in icu for severe burned burnt including any who have spent more than h with nosocomial infection (modified cdc criteria), and in which all biological and bacteriological samples were taken. the different types of infections studied were: skin, urinary, lung and bloodstream infections. they excluded all patients belatedly supported or having stayed in other healthcare facilities. results one hundred twenty ( ) patients showed nosocomial infection during this period. the sex ratio (m/f) was . and the mean age was ± years. bacteremia was present in . % of cases, followed by the urinary tract infection that was present in . % of cases, followed by the cutaneous infection in . % of cases, and last pulmonary infection in % of cases. infection was polymicrobial in . % of cases. the main bacteria identified were: acinetobacter baumanii ( . %) of which % is resistant to imipenem, enterobacteriaceae ( . %), pseudomonas aeruginosa ( %) of which . % is resistant to ceftazidime and . % is resistant to imipenem, enterococcus ( %) and staphylococcus aureus ( . %). conclusion the incidence of nosocomial infection is very high compared to literature. the rate of resistance to common antibiotics is very high. a drastic management of antibiotics in our context, the selection of patients and the frequent use in the operating room for skincare allow a better management of these patients. introduction acinetobacter baumannii (ab) ventilator-associated pneumonia (vap) is common in critically ill patients. the aims of this study were to describing the epidemiological characteristics of ab-vap, to identify risk factors for acquisition and factors predictive of a poor outcome. materials and methods a retrospective-prospective study was conducted at the medical intensive care unit of the university hospital ibn sina, rabat-morocco from january to december . they were included in the study that all patients developed vap with identified germ. for identification of risk factors of acquisition of ab vap, two groups of patients were compared: patients with ab vap versus patients with vap caused by other germs. to identify factors associated with mortality, two other groups were compared: survivors versus died. results patients presented vap among which were caused by acinetobacter baumannii. among isolates of ab, . % were drug susceptible, and . % were multidrug-resistant while % were extensively drug-resistant. they were independent risk factors for acquisition of ab vap in multivariate analysis: the presence of a central venous catheter before the occurrence of vap, duration of prior hospitalization ≥ days and icu duration of stay ≥ days. the mortality rate of ab vap was %. the independent risk factors for poor outcome in multivariate analysis were: duration of antibiotic treatment > days, the reintubation and the presence of a previous hospitalization. discussion our data were similar to those of the literature with a high incidence of vap due to the ab ( %) and a high rate of resistance to this bacterium particularly to carbapenems. however, and compared to the literature, the vap ab were responsible for a death rate much higher ( %). conclusion our data were similar to those of the literature with a high incidence of vap due to the ab ( %) and a high rate of resistance to this bacterium particularly to carbapenems. however, and compared to the literature, the vap ab were responsible for a death rate much higher ( %). introduction ventilator-associated pneumonia (vap) is common in critically-ill patients. in fact, - % of patients requiring invasive mechanical ventilation develop this complication. the onset of vap has been reported to be associated with increased mortality. however, data related to critically-ill elderly patients are scarce. the aim of this study is to assess the prognostic impact of vap in critically-ill elderly patients. patients and methods mono-center, retrospective study conducted from / to / / . all old patients (age ≥ years) requiring mechanical ventilation were included. two groups were compared: patients who developed vap (vap (+) group) and those who did not develop vap (vap (−) group). results during the study period, patients were included. the causes of admission in the intensive care unit (icu) were shock (n = ), acute respiratory failure (n = ) and disturbed level of consciousness (n = ). diabetes mellitus, hypertension and chronic obstructive pulmonary disease were the most common comorbidities ( . , . and . % respectively). mean age was . ± . years. sex-ratio (m/f) was . . mean apache(ii) score was ± . the mean duration of mechanical ventilation was ± days. thirty patients ( . %) developed vap. icu-mortality was significantly higher in the vap (+) group ( vs . %; p = . ). multivariate analysis identified two independent factors predicting icu mortality: shock on admission (or = . , ci % [ . - . ], p < . ) and vap (or = . , ci % [ . - . ], p = . ). conclusion vap is common in critically-ill elderly patients and is associated with worse outcome. therefore, preventing its onset is of paramount importance. increased health-care costs. among pathogens responsible of vap, acinetobacter baumannii which is characterized by its ability to spread in the hospital environment and to acquire resistance leading sometimes to therapeutic impasses is associated with a particularly high mortality reaching - %. objective to describe the epidemiological characteristics of a. baumannii vap, to determine their prognosis and identify factors associated with mortality. patients and methods it is a monocentric observational study conducted over a period of years in a tunisian intensive care unit (icu) including mechanical ventilated patients for more than h with confirmed a. baumannii vap. results one hundred and twenty-three patients were included in the study. a. baumannii was responsible for % of vap in our icu. the vap were late in % of cases. more than % of isolates pathogens were resistant to ticarcillin, piperacillin, piperacillintazobactam, ceftazidime and ciprofloxacin. sixty percent of germs were sensitive to imipenem. resistance to imipenem has increased consistently from % at the beginning of the study to % in . all pathogens were susceptible to colistin. a. baumannii vap was complicated by septic shock in % of cases. the median duration of mechanical ventilation and of icu stay were (iqr: [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and days (iqr: - ) respectively. the use of parenteral nutrition was the only factor associated with the occurrence of a. baumannii vap resistant to imipenem (odds ratio . , % ci [ . - . ], p = . ). icu mortality was %. it was higher in patients with a. baumannii vap resistant to imipenem ( vs %, p > . ). in the multivariate analysis, the age, the use of renal replacement therapy and the occurrence of vap relapse have been identified as factors associated with mortality. conclusion a. baumannii resistance to imipenem became threatening. the use of parenteral nutrition was the only factor associated with the occurrence of a. baumannii vap resistant to imipenem. the choice of empiric antimicrobial for vap caused by this pathogen must take in consideration the epidemiologic data of each country and each icu. a. baumannii vap was associated with high mortality. the age, the use of renal replacement therapy and the occurrence of vap relapse have been identified as predictive of poor outcome. none. admission in intensive care unit for severe adverse drug event: what finding? julien arcizet , bertrand leroy , caroline abdulmalack , catherine renzullo , maël hamet , jean-marc doise , jérôme coutet introduction adverse drug events (ade) remain a serious public health problem. they represent between . and . % of hospital admissions and between . and . % of intensive care unit (icu) admissions. they are defined as any injury related to a drug, and include both adverse drug reactions, expected or not, but also underuse, overuse and misuse, unintended or undesired, preventable or not. indeed, mortality from iatrogenic event would rise between . and . %, whereas these ade that resulted in icu hospitalization could be prevented in . - . % of cases. these unplanned admissions overload icu, limit access to health care for other patients and have serious economic consequences for the health system. it is therefore necessary to study these ade to know their main causes and attempt to find a solution to avoid them. the main objectives of our study were to clinically and pharmaceutically analyze and stratify the different ade leading to hospitalization in our icu. this is a monocentric prospective study, between june to january , in medico-surgery icu. from all admissions, we had included patients admitted in our hospital for involuntary ade (plausible, likely and very likely causal). we had collected clinical aspects (failure mode, igsii score, mortality in icu) and pharmaceutical aspect (number of drug, offending drugs) at daily medical staff meeting. conclusion hospitalizations in icu for ade are still too common despite their preventability for most cases. many patients with known cognitive disorder manage their treatment themselves and this is probably one of the reasons of iatrogenic events. anticoagulants and antiplatelet agents, by side effects, misuse, underuse or overuse are very often involved. the onset of kidney failure from dehydration and the continuation of nephrotoxic and antidiabetic treatment also remain one of the most common causes. consequently, it is necessary to continue and develop primary, secondary and tertiary prevention strategies to prevent their appearance, to limit their consequences and to reduce recidivism. introduction intensive care unit (icu) is usually identified as a place of acute care, concentrated over a short period. for many reasons, a prolonged stay in the icu has a pejorative connotation for the intensivist physician. the aim of our study is to describe the epidemiological, clinical, paraclinical profile of patients hospitalized for a long time in icu (over days) and to identify the main prognostic factors and those that can predict the duration of stay in icu. we conducted a retrospective study, over a period of years and months (january to june ), enrolling patients whose length of stay was greater than or equal to introduction despite an improvement in prognosis of patients with hematologic malignancies for the last decade, mortality of such patients admitted to the intensive care unit (icu) remains high. yet, it seems that a first icu stay does not modify prognosis of the malignancy. until now, there is no data on readmission in the icu of such patients and its effect on short and long term prognosis impact. patients and methods this retrospective, single-center study conducted on a years period in the medical icu from our university hospital included patients with hematological malignancies admitted for a first stay. objectives were to evaluate the icu, day and months mortality, to identify prognostic factors associated with mortality within uni-and multivariate analysis, to evaluate readmission rate within the days after discharge, to indentify the admission risk factors associated with icu readmission and the prognosis factors associated with mortality during the second icu stay. multivariate analysis poor performance status, igs ii, hlh, mv and anti-fungal administration were associated with increased icu mortality, infections with pseudomonas were associated with higher day mortality. catheter related infections were associated with better icu survival and cr was associated with lower day mortality. of ( . %) candidate patients for icu readmission after a first stay were readmitted within the days following discharge. median overall survival was lower in readmitted versus non readmitted patients. months mortality was . % for readmitted versus . % for no readmitted patients (p < . ). the second icu stay mortality was . % and month mortality was . %. by multivariate analysis, only mv was associated with prognosis. the months mortality rate of patients who survived to the second icu stay was significantly higher than the patients who survived to the first admission but were not readmitted ( . vs . %, p = . ). conclusion main features, short and long term mortality and prognostic factors associated with icu admission are in lines with previous studies. early readmission rate was high with a negative impact on survival. despite admission in the icu of patients with hematologic malignancies seems not to affect long term prognosis, early readmission seems to have a pejorative impact on the course of the malignancy. introduction lung cancer is among all types of cancer, the most common solid tumour admitted in intensive care [ ] . recent studies showed that the prognosis of patients with lung cancer during intensive care unit (icu) stay has improved [ ] . the aim of our study was to determine the causes of icu admission of lung cancer patients, their prognosis and to identify factors predicting hospital mortality and survival after hospital discharge. in fact, temporary full-code icu management in patients with relapsed aml seems to be appropriate. none of the life-sustaining interventions at admission and on day were able to predict survival. an icu trial of days might not be enough to appraise precisely the outcome. bone marrow transplant was associated with a high mortality in our study. in case of relapsed aml with bmt, icu management is still challenging. the growing population of chronically critically-ill patients has a poor prognosis despite all the resources mobilised [ ] . our primary objective was to analyse the prognostic value of different definitions used to describe them. our secondary objective was to look for early clinical and biological factors that could be associated with the in-hospital mortality. we conducted an epidemiological prospective study in intensive care units (neurosurgical, cardiosurgical and medical) of a large french teaching hospital (henri mondor, créteil). we included all the patients hospitalized for at least days. we tested definitions: the prolonged mechanical ventilation, the definition taken up by kahn et al. [ ] , the prolonged length of stay, the persistent critical illness and the persistent inflammation-immunosuppression and catabolism syndrome. two biological examinations were performed: upon entering the study and week later. the study endpoint was the in-hospital mortality. results thirty patients were included between april and july . among them, only % matched the definition of prolonged mechanical ventilation, which is still the most used in the literature. further, it was not associated with the mortality, but the prolonged length of stay was, with % of these patients, that did not survive to their hospital stay. other parameters that were significantly different between the patients who died and those who survived were an advanced age, an elevated igs ii score at hospital admission, an elevated sofa score at study entry, a late healthcare-associated infection and several biological variables: a high c reactive protein, low albumin and prealbumin and a poor percent of monocytes expressing hla-dr, all measured at day . conclusion the in-hospital mortality of chronically critically-ill is still high. a prolonged length of stay is the only definition who may be helpful to identify the patients with the poorest outcome. among the early factors associated with mortality, we found a late healthcareassociated infection and a low percent of monocytes expressing hla-dr, pointing to the value of studying the immune system of these patients. introduction as a result of demographic transition, the proportion of «very elderly» (≥ years) patients is increasing worldwide and more of these patients are nowadays admitted to intensive care units (icu). among physicians the discussion about appropriateness of these icu admissions still remains controversial mostly due to questionable outcome, limited resources and costs. the aim of the study was to determine and evaluate the clinical characteristics and outcome in a very old population admitted to a medical icu in an urban teaching hospital. we present here a monocentric, retrospective and observational study. we reviewed the charts of all patients (≥ years) admitted to a medical icu between and ( years). we collected epidemiological, clinical and biological parameters and all therapeutic measures during the icu stay. a longterm survival follow-up was also performed. two hundred eighty-four patients were included for statistical analysis. multivariate cox regression was also performed to identify risk factors for -day outcome. results a total of patients were included, which represented . % of admissions to the icu during the period of the study. the mean age was . ± . years, the sex ratio was . . most of patients ( %) were admitted from the emergency department. % of these admitted patients suffered of previous dementia. the mean charlson comorbidity score was . ± . and the mean mccabe score was . ± . . the admission diagnosis in the icu was mainly respiratory distress ( %), septic shock ( %), cardiac arrest ( %) and coma ( %). the mean saps-ii score within h of icu admission was . ± . . half of these patients required support by mechanical ventilation (mean duration . days) and vasoactive drugs and % of patients received renal replacement. icu and in-hospital mortality rates were and % respectively. overall survival at months after hospital discharge was %. multivariate regression revealed necessity of catecholamines and mechanical ventilation as independent risk factors and urinary sepsis as protective factor for -day outcome. in fine, for % of these patients, a limitation of active treatment was decided (on average after days of stay). for all others there was no justification for limiting care because of a well-established treatment plan (with family, gp, icu team). conclusion the proportion of elderly patients remains low, but they are increasingly being treated in intensive care units. nevertheless, the in-hospital mortality is high compared to the average mortality in our icu over the same period ( %). the prognosis is often not as poor as initially perceived by physicians. the indication for icu treatment in our study was mostly justified; in the setting of consistent patient care and good clinical practice. it remains therefore appropriate to discuss every single icu admission of elderly patients without any restriction related to age. thus, the ongoing cluster-randomized trial of icu admissions for the elderly patients (ice-cub study) is deeply awaited to confirm or not these results [ ] . keywords intensive care; prognosis; outcome; elderly patients; over -years old. introduction regardless of the route of delivery, the postpartum hemorrhage (pph) is defined as blood loss ≥ ml after childbirth, and severe pph as blood loss ≥ ml. pph is the leading cause of maternal mortality in africa. the aim of this prospective study was to assess the quality of the initial management of pph in algeria in oran ehu and to determine the factors of care with the severity of this complication. we conducted a prospective cohort study between april and september at the ehu oran. all women who delivered vaginally and showed hpp including the suspected cause was uterine atony were included. the severe pph was defined as bleeding that required invasive surgical treatment (hysterectomy, arterial ligation), a transfusion, a transfer to an intensive care unit or death of the patient. the quality of care was evaluated using objective criteria defined by a delay of diagnosis and care and mortality. results among the women who delivered vaginally during the study period, had a pph, link with uterine atony alleged at diagnosis, of which presented signs of severity. in % of cases, the delay in diagnosis of pph was less than min; % of women received oxytocin within min after diagnosis. the tranexanique acid was used in case. the examination of the cervix, uterine exploration and uterine massage was performed in , and %, respectively. the failure of first line treatment involved % of patients. among them, the time between the diagnosis of pph and administration of blood derivatives was greater than h in a third of cases. the administration of oxytocin delay exceeds min multiplied by . the risk of severe pph. however we had deaths in our series. discussion in our study the optimal period of care was not adequate, obtaining blood derivatives in our institution remains among the factors aggravating among the main risk factors for pph, uterine atony was the main source of complication. bleeding postpartum aggravated in our two patients has led to the deaths from late diagnosis and care that was not optimal. these hemorrhages pp is the leading cause of mortality: % of obstetric deaths ( % in the confidential survey - ) [ ] . a hysterectomy was indicated after failure to conservative treatment. the death rate is estimated at % following a disorder complicated hemostasis of disseminated intravascular coagulation (dic). in some series, the mortality rate is estimated between and % [ ] . conclusion the management of pph in obstetrics gynecology service the ehu oran was not optimal. the issue of timing of diagnosis and initial treatment is crucial. solutions must be sought locally to ensure the administration of essential medicines in time, especially the injection of oxytocin within min after diagnosis. introduction chronic obstructive pulmonary disease (copd) is a common pathology that would represent the third cause of death worldwide by . its evolution is interspersed with episodes of acute exacerbations (aecopd) that may indicate an admission in intensive care unit in the most. objective to study the evolution of management modalities of patients admitted in our intensive care unit for aecopd, to determine their prognosis and to identify factors associated with mortality. patients and methods it is a retrospective, monocentric study, performed in a tunisian intensive care unit (icu) over a period of years. we including all patients admitted in icu for aecopd. parameters collected were demographic features, comorbidities, regular treatment, dyspnea assessed by the mrc scale, initial clinical severity reflected by saps ii and apache ii scores, modalities and icu admission deadlines, initial arterial blood gas analysis, management of patients in the icu (ventilation modalities, prescription of antibiotics, use of vasoactive drugs) and their outcomes (incidence of nosocomial infections and their sites, length of stay and icu mortality). results a total of patients, which represents . % of all hospitalizations, with mean age of years (iqr: - ) were admitted for aecopd during the study period. the mean saps ii and apache ii were respectively (iqr: - ) and (iqr: - ). of these, % were ventilated with niv whose overall failure rate was % with a significant decrease between the beginning and the end of the study ( vs % p = . ). sixty-four percent of patients received antibiotics at admission. the prescription rate of antibiotics has decreased significantly over the years from to %. the incidence of nosocomial infections was %. it remained steady between and %. their sites were pulmonary in % of cases. icu mortality was %. in multivariate analysis, icu admission deadlines, niv failure and the use of vasoactive drugs were identified as factors associated with mortality. conclusion our study showed the importance of aecopd in the activity of our icu. the management of these patients has evolved over the years, which was reflected by the significant decrease in the prescription of antibiotics and the enhancement of niv success rate. this result could be attributed to the combination of several factors: precocious management of patients, experience of the healthcare team and the use of efficient ventilators. icu admission deadlines, niv failure and the use of vasoactive drugs were identified as factors associated with mortality. introduction aim. investigate the effect of music therapy on the tolerance of non-invasive ventilation (niv) during its introduction. currently, % of the trauma are intubated. thirty-three percent of the patient admitted in intensive care suffers from acute respiratory distress syndrome (ards). the fmhs chose oxygen concentrator as oxygen source in addition to oxygen pressurized bottles. their supply can be uncertain in conflict areas. insufficient data are available concerning the use of oxygen concentrator in intensive care unit. the primary endpoint was to determine over the total duration of oxygen therapy, the number of days on which the use of pressurized oxygen was needed for patients oxygenated by oxygen concentrator. the secondary endpoints were to identify when pressurized oxygen was needed, describe the characteristics of the population with oxygen therapy and estimate the oxygen quantity economised thanks to the use of oxygen concentrator. the study took place in the forward surgical unit of bouffard. it's a french role located in djibouti republic in africa. all patients over admitted in the intensive care and needing oxygen therapy were included. all the patients were oxygenated with an oxygen concentrator. the oxygen concentrators used were sequaltm integra om, that could deliver up to l/min of normobaric oxygen. the ventilator used were pulmonetictm ltv and . results thirty-six patients were included over the months' study period. sixty percent of the patients were men with an average age of two hundred and fifty-one days represents the total number of days of oxygen therapy divided into days of invasive ventilation, days of noninvasive ventilation and days of oxygen mask. the use of pressurized oxygen was necessary times over the days of oxygen therapy which represents . % of the total time. the causes of its use were in ten cases ( . %) criteria of severe ards, in six cases an emergency intubation and in three cases a transfer. one dysfunction of an oxygen concentrator happened during our study. the oxygen concentrator produced m of oxygen over the study period, which represents oxygen pressurized bottles of litres. this enabled an economy of , euros. conclusion it is safe to use oxygen concentrator to take care of critically ill patients in limited resources environment. the use of pressurized oxygen is still compulsory in two situations: in case of electricity failure and in case of high fio (above %). oxygen concentrators are sufficient in . % of the time. they enable to deliver oxygen any time which is essential when supply is uncertain in conflict areas. none. table ). for the same mv and level of ofr, fdo was in our experiment, with an ofr of l/min, when ifr = l/min (mv = l/min and ti/ttot = . ), the fdo is equal to % (± %) (see table ). to this value of ifr, the fdo is in accordance with the formula of ats, but when ifr increase beyond l/min, the fdo decrease and the formula is not in accordance with ats. this can be explain because during inspiratory phase, air room (fractional oxygen = . ) entry in airway mixes with ofr (fo = ), which modifies the fdo . in this case, when ifr increase then fdo decrease and vice versa. medical and paramedical staff must be aware that with patients who receive ofr by nasal cannula, any change of ofr and/or inspiratory flow changes the fdo . in this case, for maintain the same fdo , it is necessary that modify the value of ofr. the actual fio delivered under oxygen mask in patients with acute respiratory failure and the factors that may influence the fio are poorly known. in clinical practice, different methods including formula or conversion tables based on oxygen flow can be used to estimate delivered fio . we aimed to assess first the factors influencing measured values of fio , and second the best method to estimate fio in patients breathing under oxygen mask. we included icu patients admitted for acute hypoxemic respiratory failure from a previous prospective trial [ ] in whom fio was measured under oxygen mask using a portable oxygen analyzer. we collected demographic variables and respiratory parameters that may influence measured fio . low fio was defined according to the median measured fio . for each patient, measured fio was compared to "calc + %" formula (fio = oxygen flow in liters per minute × . + . ) to "calc + %" formula (fio = oxygen flow in liters per minute × . + . ), and to a conversion table [ ] . a ± % limit of agreement for each estimation method was arbitrarily considered acceptable. results among the patients included, median measured fio was % [ - ]. after adjustment on oxygen flow, the three variables independently associated with low measured fio using multivariate analysis were patient's height, a low paco , and a respiratory rate greater than breaths/min. using paired analysis, each estimation methods differed significantly from measured fio (p < . for each). values outside the limits introduction acute hyperglycemia is common in intensive care. it was associated with poor prognosis and increased mortality. the purpose of our study is to investigate the frequency of hyperglycemia in our icu, to determine the main causes of high blood sugar and to analyze the impact of this hyperglycemia. our study is prospective during months. it was conducted in the intensive care unit of the university hospital habib bourguiba sfax-tunisia. were included in our study all patients admitted to the service during the period of the study. for each patient included were collected from the icu admission, clinical and biological data. results during the study period, patients were hospitalized in our icu and the diagnosis of hyperglycemia (> mmol/l) was admitted in patients ( %). the comparison between patients who developed hyperglycemia and those free hyperglycemia group showed that, the patients of the first group were significantly older (p < . ). additionally, hyperglycemic patients had more medical history including history of diabetes (p < . ), a higher saps ii (p < . ), a more significant frequency of active infections (p < . ). moreover, the presence of hyperglycemia was associated with shock (p < . ) and respiratory distress (p < . ). their evolution was marked by the significantly higher frequency of infectious complications (p < . ), thromboembolic complications (p < . ) and acute renal failure (p < . ). the average duration of mechanical ventilation and the length of stay were also significantly prolonged in hyperglycemia group patients (p < . for both). finally, the presence of hyperglycemia was significantly associated with a higher mortality rate. conclusion we concluded that hyperglycemia is correlated with poor prognosis of morbidity and mortality. but strict glycemic control remain controversial. thus, further studies on this subject will be recommended to define the exact place of glycemic control in intensive care. none. the rrt was prophylactic in four cases started when phophatemia was more than mmol/l, and therapeutic for renal failure and established tls in three cases. the median duration stay in icu was [ ] [ ] [ ] [ ] j. thirteen patients left the icu without major metabolic dysfunction. two patients deceased due to infectious complications. discussion monitoring of electrolytes was done on average, three times a day which is hard to do in onco-hematology unit. the early use of rasburicase and the aggressive iv hydration helped to prevent tls for seven patients. the aggressive iv hydration was made according to echocardiography data and close monitoring of vital signs and urine output which has allowed to avoid volume overload and acute pulmonary edema. the early prophylactic rrt prevented renal failure and metabolic complications. conclusion early management of tls in icu can prevent tls and most of its serious complications and should be considered in tls prophylaxis recommendations. none. the both urinary (expressed as the ratio of ngal on urinary creatinine) and plasma ngal were predictive of aki stage . predictive value of plasmatic measurements was higher than the urinary one (auc of . and . , respectively, p = . between auc), but not higher than either baseline serum creatinine (auc = . ) or h diuresis (auc = . ). backward multivariate regression showed that plasma ngal concentration was associated with serum creatinine, crp and albumin, whereas urinary ngal was associated with leucocyturia and baseline creatinine. discussion previous positive studies with ngal did not compare the performance of this costly biomarker with simple usual clinical parameters to predict aki. moreover, several parameters were associated with ngal concentrations with a high risk of collinearity (crp) and/or false positive results (leucocyturia). our data do not support any added value of ngal concentration over baseline serum creatinine or urine output to predict aki. introduction acute renal failure (arf) is a common entity in intensive care, concern that the heavy morbidity and mortality it is associated [ ] . early diagnosis of this entity remains difficult, neither diuresis and creatinine are early parameters in the diagnosis of arf. the kidney is an organ that suffers long to become faulty, the priority is to recognize renal aggression and to achieve a therapeutic allowing reversibility of the infringement. a number of markers have been developed for the diagnosis of the ira but costs remain high not allowing their routine use. the measurement of resistance index with the renal doppler could be a solution for the diagnosis of aggression and also of the etiology. the elevation of creatinine was seen later within h after the ir > . discussion in our series the resistance index has a value of early diagnosis of renal prognosis aggression in the occurrence and development of renal failure. renal doppler associated with a strictly applied standardized protocol achieves the two goals of monitoring who aid in the diagnosis and guide treatment. although the recommendations of experts to this tool provides that it should probably not use the resistance index measured by renal doppler to diagnose or treat an ira (grade ) [ ] . identifying the cause of kidney aggression is a prerequisite before any therapeutic action. hypovolemia and soda hydro overload are the causes principales. excess filling hyper intra thoracic pressure and hypoxia are the main causes of kidney congestion. conclusion doppler is an early renal medium in the diagnosis of renal aggression. a larger series could assert this observation. none. ), had significantly more pre-eclampsia, / ( %) versus / ( %) p = . . pe were started at an average of . days after foetal extraction, and with an average of sessions. patients of the pe group had significantly lower nadir of hemoglobin but also lower hemoglobin level at day and day . nadir of platelets count was also lower and level remain lower at days , , and . acute kidney injury (using kdigo classification) was more frequent with a higher rate of dialysis in icu, in the pe group ( / ( %) vs / ( %) p = . ) with a more frequent need for dialysis at the exit of icu. proteinuria was significantly higher in the pe group ( . mg/mmol vs . mg/mmol, p = . ). adamts dosage was done only in patients with pe. we find a diminution of adamts activity (before pe) with an average of % [ - ] in this group. there was no death, and adverse effects were not significantly different. discussion this study shows that pe was used when diagnosis was uncertain in the most severe form of pp-tma. low hemoglobin, low platelets, acute kidney injury and high level of proteinuria are the main factors associated with the decision to begin pe. this technique was safe and not associated with major adverse events. several studies show that there are physiopathological crossovers between diseases associated with pp-tma, for example low adamts activity in hellp or mutation in alternative complement pathway which induced hellp. moreover, studies and case reports show a benefit of pe in hellp syndrome. our study did not find significant difference in adverse events (maybe due to a lack of power), but this is another argument to discuss pe in the management of pp-tma in severe patients. the main limits of our study are that none of the patients who had a plasmatic exchange had a diagnosis of ptt and that diagnosis tests were not performed in all patients with pp-tma (complements level, adamts …). conclusion pp-tma treated with pe has lower hemoglobin, lower platelets, higher rate of kidney injury and proteinuria than those treated without pe. no difference were found for adverse events. begining of pe should be discussed for management of a pp-tma without amelioration after foetal extraction. none. introduction diffuse alveolar damage (dad) is the typical histological feature of acute respiratory distress syndrome (ards). however, in a previous study including patients with criteria for ards, we found that only % of them had dad at autopsy exanimation [ ] . it has been shown that patients with ards and dad on open lung biopsy had higher mortality than those without dad [ ] . thus, we aimed to identify markers associated with dad in patients with ards. we included the patients who met criteria for ards at time of death in our large database of clinical autopsies [ ] . we assessed the proportion of dad according to the severity of ards including the degree of hypoxemia and the ancillary variables from the berlin definition: use of high levels of positive endexpiratory pressure (peep at least cmh o), radiographic severity ( or quadrants on chest radiograph), altered respiratory system compliance (≤ ml/cmh o), and large dead space defined as a corrected expired volume per minute (≥ l/min). results dad was associated with all the severity markers abovementioned using univariate analysis. after multivariable logistic regression, the three markers independently associated with presence of dad were the gender with an odds ratio ( conclusion dad was significantly more frequent in females. in addition to the severity of hypoxemia, diffuse infiltrates involving the quadrants was a significant marker of dad. introduction ventilation induced lung injury (vili) is responsible for an increased mortality in ards [ ] . mechanical ventilation may trigger an inflammatory response, comprising alveolar macrophage activation and recruitment, which may be specifically, repeatedly and spatially assessed by functional imaging techniques such as positron emission tomography combined with computerized tomography (pet/ct) [ ] . c-pk is a pet radiotracer with potential to quantify macrophage inflammation. we aim to assess its performance to detect lung macrophage recruitment in an experimental highvolume vili model. materials and methods vili was performed in anesthetized pigs under neuromuscular blockade by rapidly increasing the tidal volume (vt) to obtain a transpulmonary pressure (tpp) between and cmh o under zero end-expiratory pressure. pet/ct acquisitions were performed before (t ) and after h of high-volume ventilation (t ), and image-derived measurements were realized on the whole lungs, and regionally on distinct lung regions (divided along the anteroposterior and the cephalocaudal axes). c-pk lung uptake was estimated using the standardized uptake value (suv), normalized to the ct-derived tissue fraction in the region of interest (roi). mechanical lung aggression was estimated by ct-derived dynamic and static strains, and tidal alveolar hyperinflation (expressed as a fraction of the tidal variation in the roi volume). after euthanasia, alveolar damage and macrophage recruitment were assessed in the lung regions, using semi-quantitative scores. results between t and t , vt and tpp significantly increased from . ± . to . ± . ml/kg and . ± . to . ± . cmh o, respectively. suv on the whole lung significantly increased from . ± . to . ± . between t and t and dynamic strain from . ± to . ± . , whereas static strain did not significantly vary. tidal alveolar hyperinflation significantly increased from ± to ± % on the whole lung between t and t . regionally, dynamic strain, and tidal alveolar hyperinflation significantly differed between regions, as well as between t and t . regional suv differed between t and t but not between regions. regional static strain did not differ between regions, nor between t and t . in multivariate analysis, regional suv was independently and significantly associated with dynamic strain and tidal alveolar hyperinflation. histologic analysis showed significant regional differences in alveolar damage but not in macrophage recruitment. suv was positively associated with macrophage recruitment but not with alveolar damage. discussion in this experimental vili model, c-pk suv was significantly increased after h of injurious ventilation, and was significantly and positively associated with high-volume ct-derived mechanical parameters, such as dynamic strain and tidal alveolar hyperinflation. the radiotracer's specificity for macrophages is confirmed by the suv significant association with macrophage recruitment and the lack of association with alveolar inflammatory edema. conclusion c-pk is a macrophage-specific pet radiotracer, with potential to dynamically and specifically assess alveolar macrophage inflammation induced by high-volume ventilation. research founded by the french society of intensive care medicine (srlf) and la fondation pour la recherche médicale (dea ). the reverse triggering (rt) is the term used to name the contractions reflexes of the muscle diaphragmatic provoked ("triggered") by the periodic insufflations, delivered by the ventilator, at sedated patients under mechanical ventilation [ ] . the rt constitutes a new form of patient-ventilator interaction clinically difficult to detect and little known. the rt could have potential implications during the management of acute respiratory distress syndrome (ards). at present, the management of severe ards consists among others, on the use of an early and systematic perfusion of neuromuscular blockade agents (nmba) during a h' period, continuation to the acurasys essay which showed a reduction of the mortality in the group of the severe ards patient receiving nmba. the reason of the beneficial effect of curare is not perfectly known. it is possible that the phenomenon of rt is a mechanism implied in the deleterious role of the mechanical ventilation during ards. the abolition of this phenomenon by nmba could explain the beneficial effect of nmba in ards [ ] . the objective was to look for the phenomenon of rt in two groups of ards patients: a group receiving nmba and a group not receiving nmba. patients and methods physiological observational and comparative study in intensive care units. we record continuous signals of airflow, airway pressure, and esophageal pressure during h of consecutives patients with ards criteria and pao /fio ratio ≤ at a positive end-expiratory pressure (peep) of cmh o evolving for less than h under mechanical ventilation. recording of esophageal pressure of consecutives moderate to severe ards patients were blinded analyzed (group nmba n = ; group unless nmba n = ). any phenomenon of rt was observed in the group of mild ards patients receiving nmba (fig. a) . we confirmed the existence of rt on patients of in the group of mild ards who not receiving nmba (p = . ) (fig b) . discussion one of the main limits was the quality of the collection of the signal of esophageal pressure. the monitoring of esophageal pressure is technically difficult, and can d influence the quality of the signal and the reliability of the results. conclusion this study confirms the existence of the phenomenon of reverse triggering among deeply sedated patients not receiving nmba with a % incidence. more research is needed to determine if the reverse triggering is a risk factor independent from vili, associated with the bad prognosis of severe sdra patients and, if a strategy of early treatment based on nmba, could improve the prognosis of reached patients. after ecmo removal had a significant median reduction of days in the bipap-aprv group, p = . (fig. ). we reported the feasibility of a protocol based on bipap-aprv aiming at resuming sv as soon as possible in ards patients under ecmo. the occurrence of spontaneous inspiratory efforts in ards patients can major variability of transpulmonary pressure and as result jeopardise vt and driving pressure control. this might be an issue if protective ventilation is not guaranteed anymore. vt with bipap-aprv remains within safe range when the ratio fig. circles are pac group, rhombus are aprv group. mv mechanical ventilation, psv pressure support ventilation. data are presented as median (iqr), comparison between the groups at each time mann-whithney test, *p < . of spontaneous minute ventilation to total minute ventilation is between and % [ ] . bipap-aprv is more efficient than psv to increase lung aeration in patients with ards [ ] . recruitment of dependent region is more likely to achieve if sv is not supported by synchronized positive airway pressure as during bipap-aprv [ ] . our strategy targeting a percentage of sv between and % with high peep could be viewed as a compromise in order to promote sv and protective ventilation at the same time. conclusion protective ventilation combined with sv under ecmo by using a specific protocol based on bipap-aprv is feasible and safe. it may facilitate weaning and thus reduce the time under mv after ecmo. to what extend this beneficial effect is directly due to the presence of sv deserve further investigations. introduction since the first transplant from a patient in a state of brain death conducted in at the university teaching hospital ibn rushd of casablanca, the number of transplants has increased. however, it is still inadequate meet the growing needs of organs. the refusal of families remains the main obstacle to the developpement of organ transplantation in morocco. the aim of our study is to monitor and analyse the evolution of family refusal to organ donation in a brain dead patient. patients and methods this is a retrospective and comparative study from august until december .the data were collected from records of brain dead patients candidates for organ donation at the intensive care units on ibn rushed hospital. the coordination registers were also studied. a questionnaire was distributed to families who refused organ donation to investigate the causes of the refusal. results during this period, patients with brain death have been identified and families had been approached. families ( %) refused organ donation. the main causes of refusal were: fear of body mutilation ( %), lack of will ( %) and religious causes in % of cases. the refusal rate for families decreased from % in to % in . only patients experienced cardiac arrest before transplantation. during this period, cornea transplants from braindead patient were conducted with kidney transplants and two liver transplants. discussion the evolution of the refusal of families saw a decline through awareness and communication campaigns for organ donation. conclusion improvements to our health care system must be proposed including strengthening detection of potential donors and relationships with the donor's family and effective communication policy. in the icu, three major actors are involved in the caring relationship: patient, relatives and caregivers. acting as spontaneous testimonials of the lived experience, thank-you letters from relatives may be considered by icu teams as a source of original information which could help in improving care for critically ill patients and families. this study aimed to investigate the qualitative content of thank-you letters from relatives of patients who stayed in the icu. specifically, our research questions were, with regards to the letters' content, ( ) how is the caring relationship tackled and characterized by relatives? ( ) to what extent does this relationship impact their experience of icu? materials and methods the study took place in a -beds icu during a -month period. the research team consisted in a care assistant, a nurse (also clinical research associate), a psychologist (not working in the icu) and an intensivist. the corpus consisted in twenty thankyou letters received in the icu. we conducted a qualitative study according to the thematic inductive approach. the process of coding was intended to create established meaningful patterns. results two main themes emerged as specific determinants of the caring relationship: ( ) the temporality, comprising the time dedicated to the patients and their family, the time spent with the icu team, the striking time corresponding to significant events for relatives needed to be shared with the staff, the extension of the link with caregivers by evocating a new life after icu stay, the writing time as a countergift to the caregivers; ( ) the caregivers behaviour, including human skills detailed in many core values (kindness, availability, devotion, attention, goodwill, sensitivity) psychological support, emotional sharing, capabilities to give informations. relatives feel to be "at the center of all attention" in the same way as their loved ones. through the narration of icu experience, the caring relationship is characterized as follows: ( ) the caregiver becomes a close person with an equal relationship (feelings of friendship, emotional closeness); ( ) the icu team becomes a new family (contrasting with the poor living environment of icus); ( ) the relative becomes a caregiver (with appropriation of medical terms or speaking of his loved one as a patient); ( ) the caregiver is seen as a "super-hero" through an asymmetrical relationship with an overstatement of personal dedication and investment of the staff members (abnegation, vocation, involvement). the caring relationship impacts relatives' experience of intensive care in several ways: ( ) relatives are deeply touched by caregivers' human behavior, emotional support being a source of solace and resilience in particular for bereaved families; ( ) relatives express the idea that taking care of humans is not a valued and rewarded task and the emerging awareness of hospital realities and difficulties of work in the icu; ( ) the most striking transformational change in relatives is the perception of their own vulnerability and humanity, leading them to exhibit an outward-looking attitude (for example filling out their organ-donation card), and encouraging the icu caregivers to continue their missions for the others. conclusion thank-you letters provide both encouraging and informative messages for icu teams about relational care for patients and families notably the indivisibility of the families and their critically ill loved ones. the relatives' experience of the icu appears strongly influenced by the caring relationship in the way they express an authentic revelation of their own humanity and altruistic thoughts. the thematic content of thank-you letters questions determinants and fundamental values at stake in the patient-relatives-caregivers relationship. introduction far from medical paternalism, the doctor-patient relationship has now evolved to respect "the autonomy and patients' rights". changing behavior has been gradual, while the law offered the patient the freedom to consent to care and then of expressing their wishes regarding the therapeutic intensity they would benefit, in critical situations where consent would not be possible, through advance directives (ad) [ ] . their use is of paramount interest for intensivist in many critical situations. unfortunately, the use of ad remains marginal because of the unfamiliarity of patients with their use and an appropriation default by clinicians [ ] . the aim of our study was to investigate the perspective of the coming family physician generation on advances directives. patients and methods population of interest was general practitioner fellow (gpf) from class of to . we built an online questionnaire survey about knowledge and the place they want to give to ad in their forthcoming daily clinical activity. this questionnaire was sent to gpf emails obtained by universities, unions and via the official mailing lists of different regionals classes provided by the first contacted. descriptive analysis of quantitative data was expressed as mean and standard deviation, qualitative data in number and percentage. the comparison of continuous variables was performed by the student t-test and the comparison of categorical variables by a chi test. analyzes were conducted on biostatgv website and microsoft excel ® . results gpf answered the survey, mainly from ile de france (n = ), toulouse (n = ) and lille (n = ). for gpf the majority of patients do not know the ad ( . %) and % think that those who know do not know how to use it. . % of gpf think writing ad by patients requires better information. according to them, the information should concern the support offered in the icu ( . %), the use of mechanical ventilation ( . %), dialysis ( . %) and the evolution of patients after hospitalization in icu ( . %). nevertheless information on the prognosis of chronic diseases or organ failure seems interesting for only and . % of them respectively. . % of gpf wish to propose the drafting of ad to their patients. however, only . % of them are willing to suggest ad to patients with cancer or hematologic malignancies, . % to patients with neurological and/or degenerative disorders, . % to elderly patients. discussion despite the low proportion of the population we think these observations to be of interest because we probably selected the gpf the most interested in ad as the participation was not mandatory. conclusion a large majority of young of future general practitioner is willing to be involved in the implementation of ad with their patients, however the target population remains very limited, considering that half of them do not want to discuss ad with patients suffering from diseases potentially associated with icu admission or therapeutic intensity discussion. this study was conducted in adult intensive care units in public or private hospitals in four countries: canada, france, italy, spain. in each country, health care professionals were solicited for an exploratory interview about the sources of stress in the work environment: senior physicians, residents, experienced nurses (with more than years of experience in the service) and inexperienced nurses (with less than years of experience in the service). all the interview transcripts were analysed using an inductive coding approach. results one hundred and sixty professionals ( physicians and nurses) were included in the study. eight themes emerged from the analysis, and they concerned the stress linked to ( ) patient ( ) care, ( ) team, ( ) family, ( ) institutional context, ( ) environment, ( ) organizational context, ( ) individual dimensions. in each theme, sub-themes have been identified and determine more precisely the difficulties at work. discussion our findings emphasize the complexity of work in icus and show the specifics factors not taken into account in the generic stress scales such as stress in relation with family relationships, the end of life decisions and inequity of health care. conclusion the specific stress scale should allow to better identified stress in icu and to develop measures of prevention and support and training programs. introduction intensive care units (icu) is a place where caregivers face many constraints that can affect their physical and mental health due to the use of specific care and strong emotional charge related to patient death and pain of the families. the aim of the present study is to detect anxiety disorders and/or depression among staff working in icus. on september , a questionnaire was distributed to staff (medical and paramedical) operating in icus in the university hospital fattouma bourguiba monastir, tunisia ( medical icu, surgical icu, cardiologic ccus and nephrologic intermediate care unit). this questionnaire included demographic data of participants (age, sex, marital status, length of service, psychiatric history, consumption of anxiolytic and/or antidepressant) and the hospital anxiety and depression scale (had: scale composed by items to screen the anxiety (a) and/or depression (d) among hospital staff ). results during the study period, participants completed the questionnaire ( %), % of them were women, the median age was years ± . . forty-nine participants were doctors (the majority of them residents: / ). . % of participants (all paramedics) worked on night shift, seniority of more than a year in the icu was found in % of participants. . % of staff interviewed were married and only . % of them reported consumption of anxiolytics and/or antidepressants. . and . % of the participants had respectively symptoms suggesting anxiety and depression. the median had score was (iqr = ); the medical function seems to be significantly associated with the occurrence of symptoms of anxiety and depression compared to paramedics, however the type of icu (medical/surgical icus vs cordiologic/nephrologic icus) does not appear to be related to the occurrence of symptoms of anxiety or depression (table ) . conclusion anxiety and depression are common symptoms among caregivers in icus. improved conditions of work in these units should be a target to avoid burn out syndrome. none. anxiety, n (%) depression, n (%) introduction carbon monoxide (co) poisoning is one of the common causes of poisoning specially in the cold season, which leads to a significant morbidity and mortality. we retrospectively reviewed the medical data of patients who presented to the toxicology emergency department with co poisoning during january to march . we analyzed patients' characteristics, management, and outcomes. results a total of six hundred and sixty-six patients ( female and male), aged of ± years, were included; poisoning occurred between december and february in % of cases, secondary to an indoor heating system exposure in the majority of cases ( %). the estimated duration of exposure was . ± h [ . - h], with a mean carboxyhaemoglobin (cohb) level on arrival at . ± %. neurological changes were the most presenting symptoms including headache (n = , %), dizziness (n = , %), seizure (n = , . %) and loss of consciousness (n = , . %). digestive disorders involving vomiting and nausea were observed in . % (n = ). one woman without cardiovascular risk factors developed non stsegment elevation myocardial infarction complicated by lung edema. the majority of patients (n = , %) received normobaric oxygen during h (n = ) and h (n = ). hyperbaric oxygen therapy was administered at . ata during h to patients for neurological changes (n = ), pregnancy (n = ) and elevated cohb ≥ % (n = ). mechanical ventilation was required for patients, and admission into intensive care unit in patients ( %). death occurred in cases ( . %). conclusion the carbon monoxide poisoning is a common reason for emergency department visits in winter. the physician should be aware of the serious neurological and cardiovascular complications, if symptomatic treatment and oxygen therapy regimens were not respected. none. neuro-respiratory toxicity of baclofen in the rat: study of the concentrations/effects relationships and role of gabaergic introduction baclofen, a gaba-b receptor agonist is used as muscle relaxant agent and recently for the treatment of alcohol dependence. the number of poisonings has significantly increased since this new indication. clinical presentation of poisoning mainly includes sedation, hypotonia, respiratory depression and seizures. to characterize the neurorespiratory toxicity of this molecule at high doses, we aimed at investigating alterations in sprague-dawley rat ventilation and brain electrical activity after baclofen administration and studied their reversal by gaba-receptor antagonists. materials and methods rat ventilation was investigated using plethysmography and arterial blood gas analysis while brain electrical activity was studied using eeg with one implanted frontal electrode. three baclofen doses were used including . mg/kg ( % lethal dose- %), . mg/kg ( %) and mg/kg ( %). baclofen concentrations were obtained using hplc-msms assay. we modeled baclofen pharmacokinetics and analyzed the doses/effects and effects/concentrations relationships. results baclofen induced early-onset and prolonged dosedependent sedation (p = . ), hypothermia (p = . ), eeg and respiratory depression ( . ) characterized by significant increase in the inspiratory (p = . ) and expiratory times (p = . ). significant increase in paco and decrease in arterial ph and pao were observed at mg/kg (p = . ), peaking at min. eeg showed signal slowing, burst-suppression aspects and spikes peaking at - h post-injection without normalization at the end of the experiment at h. we did reverse baclofen-induced decrease in tidal volume with saclofen (a gaba-b receptor antagonist) and interestingly no alteration of baclofen-induced respiratory depression was observed with flumazenil (a gaba-a receptor antagonist). pharmacokinetic parameters of baclofen were obtained at the three doses and were dose-dependent. significant but non-linear relationships were observed between baclofen-induced effects and concentrations. conclusion baclofen causes dose-dependent neurorespiratory toxicity in rats. however, due to increased poisonings, its safety profile at high doses remains to be established in humans. none. poisoning was deliberate in % of cases. mean ingested dose was . ± mg. the majority of patients presented to the emergency room at . ± h after ingestion. digestive decontamination was performed in . % (n = ) of patients. clinical presentation was dominated by neurological symptoms; including coma (n = ), hypotonia (n = ), hyporeflexia (n = ), agitation (n = ), seizures (n = ) and delirium in case. hemodynamic manifestations included bradycardia in patients, three of them required atropine infusion. one patient presented with hypotension responding to vascular resuscitation. sixteen cases required mechanical ventilation. aspiration pneumonia was noted in cases. mean duration of ventilation was . h ± . mean hospital length of stay was h ± . complications included ventilation associated pneumonia in one case and moderate rhabdomyolysis in cases. all patients evolved favorably. there is no correlation between coma and assumed ingested dose. conclusion baclofen overdose causes mainly neurological effects and except for bradycardia cardiovascular effects were uncommon. prognosis is good if full supportive care is administered properly. none. introduction the lack of an effective treatment for the maintenance of abstinence from alcohol has led physicians to take an interest in baclofen. beyond efficacy, safety of baclofen, prescribed in high doses, is a concern, especially in case of drug overdose. indeed, patients with chronic alcohol abuse frequently develop psychiatric disorders, and are at risk of voluntary drug intoxications. thus, we set up a retrospective study to describe morbidity and mortality associated with baclofen overdose. conclusion baclofen, prescribed in high doses, may lead to severe intoxications: self-poisonings frequently require endotracheal intubation and are associated with an increased risk of death. dialysis decreases baclofen elimination half-time but clinical relevance of this difference could not be determined. none. introduction baclofen, a gaba-b receptor-agonist with muscle relaxant properties established since , has been recently used at elevated doses to treat dependence to ethanol. the number of prescriptions has exponentially increased without an exact evaluation of its toxicity. we aimed to describe acute baclofen poisoning requiring intensive care unit (icu) admission and study the relationships between the toxic encephalopathy and the plasma baclofen concentration. we conducted a single-centre retrospective study including all baclofen-poisoned patients admitted to the icu in - . when requested by the clinical situation, repeated electroencephalograms and measurements of the plasma baclofen concentrations were performed. toxic eeg encephalopathy on a scale of zero to five was graded according to the international rating system (markand, ). plasma baclofen concentration was determined using liquid chromatography coupled to mass spectrometry in tandem developed with a quantum ultra apparatus (thermo fisher scientific) and electrospray source ionization in positive mode (limit of quantification: ng/ml). linear regression and chi- or mann-whitney tests were used as requested for subgroup comparisons. baclofen pharmacokinetics and the relationships between the toxic encephalopathy and the plasma baclofen concentration were modeled using winnonlin software v. ) were closed to the observed values reported at therapeutic doses. the relationship between baclofeninduced encephalopathy as a function of the baclofen concentrations was described using a sigmoidal emax model. conclusion baclofen poisoning may be life-threatening. toxic encephalopathy is well-described with eeg and its grade correlated to the baclofen concentration. prescribers should be aware of the dangers of baclofen which benefits to treat dependence to alcohol are still lacking. none. results initial examination suggested that an illness other than bacterial meningitis was the cause of patients' complaints. first hypothesis was meningitis receiving uncomplete dosage regimen of antibiotics. thereafter owing to apparent loss of consciousness with abnormal eyes movements, non-tonico-clonic seizures were considered meanwhile. the ratio of individuals less y-o to those equal to and greater was / %. the male to female ratio was / %. the mean duration of hospitalisation was . ± . days (extremes - days). extrapyramidal syndrome predominant on the upper part of the body was noted by paediatrician neurologists who suggested considering a genetic disease. however, signs and symptoms were present in people from different families in different areas at the same time. the definitive diagnosis made on pictures and videos of children and adults and was facio-troncular dystonia resulting from drug-induced adverse effect. four urine samples were collected in children and sent to a toxicological laboratory in france. all urine samples were positive for haloperidol meanwhile the other causes of facio-troncular dystonia were excluded, including other neuroleptics, metoclopramide, antidepressants, amodiaquine, anti-histaminic drugs, anti-epileptics, and cocaine. from january to august , hospitalisations were recorded in patients. looking for the source of haloperidol showed that tablets sold as 'diazepam' and consumed by symptomatic patients contained haloperidol as the sole active pharmaceutical ingredient, suggesting that this large outbreak was due to haloperidol toxicity from falsified diazepam. initial treatment was diazepam to relieve severe facio-troncular dystonia which was efficient but resulted in long-lasting sedation more especially in children. a dosage regimen using bipéridène administered by intravenous and oral route was refined to prevent adverse effects related to this anticholinergic agent used in children. the complete reversal of the facio-troncular dystonia was the antidotal evidence supporting the toxicological diagnostic. the mortality rate was less than % meanwhile the direct causal relationship with adr is questionable. an epidemiological study, including toxicological analysis in controls in ongoing. indeed, facio-troncular dystonia induced by haloperidol does not result from a drug overdose but is an adr occurring in about % of patients treated with haloperidol. who is involved in the inquiry related to this counterfeature involving different countries. the cause of the error is presently under investigation. discussion this outbreak emphasizes the need to consider toxicity resulting from counterfeatured medicines when facing collective atypical signs and symptoms in countries with unrestricted access to medication with limited control of qualities of the medicinal drugs. conclusion counterfeatured medicinal drug may result not only in poor efficacy but also in onset of unexpected outbreak of unknown diseases that should suggest a toxic origin. in late -early , médecins sans frontières (msf) had to face an outbreak of severe facio-troncular dystonic syndrome (ftds) in north-east congo. this outbreak resulted from counterfeature of pills sold as diazepam. toxicological analysis revealed one pill contained about mg of haloperidol. ftds induced by haloperidol does not result from a drug overdose but is an adverse drug reaction (adr) occurring in about % of patients treated with haloperidol. nine-hundred and twenty-five individuals were admitted in msf structures for ftds. the ratio of individuals less than y-o and equal to or greater of age was / %, including ( . %) of children less than y-o. initial treatment was based on diazepam which relieved ftds but resulted in long-lasting sedation, preventing given any drug by the oral route. owing to the definitive diagnosis, a shift to the use of a more specific antidote was chosen. biperiden was selected as existing in the intravenous and oral form in the swiss pharmacopea. the study was approved by the ethical committee of the ministery of health of the republic democratic du congo. patients and methods as a whole, biperiden was used in cases ( % of the total). treated children presented with severe dystonia as evidenced by inability to cooperate and to swallow. verbal informed consent was obtained from relatives. the dosage regimen to treat drug-induced dystonic syndrome in the swiss pharmacopea is as follows: for parenteral use in children, intravenously or intramuscularly: . mg/kg or . mg/m bsa every , according to response and tolerance; a maximum of four doses per day should be used. the internal msf recommendations for biperiden use in children were . - . mg/kg of body weight that might be repeated four times a day. initially, biperiden administration was administered under medical supervision by the msf referent at the scene. results there was no pediatric preparation of biperiden. accordingly, the adult preparation was used in children. the preparation contained mg of biperiden in one milliter of solvent. the initial planned dose for children of y-o and less and those up to y-o were and mg, respectively. the mg ( ml) of biperiden was diluted in ml of saline resulting in a final dilution of mg/ml. six children were treated according this dosage regimen. however, the one mg dose was either of limited efficacy while being associated in others of signs suggestive of adr, including agitation, heart rate greater than b/ min, the upper limit for children aged of y-o and less. two children greater than y-o presented severe abnormal behavior resulting in an attempt at escape. owing to question about safety, the dosage regimen was changed, as follows: mg ( ml) of biperiden was diluted with ml of saline resulting in a final dilution of . mg/ml. an initial dose of . mg was administered intravenously as a bolus dose. the effects were looked for over min. in the absence of improvement in facial dystonia, a second bolus dose of . mg was administered, a third dose could be considered min later if the ftds did not resume. the cumulative initial dose should not be greater than mg. in addition to the reversal of facial dystonia, the therapeutic effect of biperiden included the return of swallowing to normal allowing to give further doses of biperiden by the oral route for three days. the first oral dose was administered no less than h after the last initial dose at a dose equal to the efficient initial cumulative dose. the following doses were halved every h. no adr related to biperiden were reported using this dosage regimen. the mean duration of hospitalisation was . ± . days. discussion the bioavailability of biperiden by the oral route is equal to %. accordingly, the corresponding intravenous dose should be divided by a factor three. dosage regimen of anticholinergic drugs in children are poorly documented. the dosage regimen recommended by the pharmacopea resulted in frequent and severe adr. titration of biperiden resulted in efficient and safe dosage. conclusion when biperiden administration is required by intravenous route in children of y-o and less, biperiden should be administered intravenously and titred using bolus dose of . mg till the therapeutic effect is obtained. introduction severe poisoning by rodenticides is frequent. it represents nearly % of patients admitted to the new intensive care unit (icu) of the region. that is why we decided to perform this study. the aim of this work was to describe the epidemiology, clinical features and management of all patients admitted to our unit for acute poisoning with rodenticides. patients and methods it was a retrospective study performed in the year from january to december. the study included all patients admitted in the icu for rodenticide poisoning. results patients were enrolled in the study. our patients were young with a mean age of ± years. poisoning was more common in females (n = ; %). the mean delay between rodenticide poisoning and first medical contact was about ± h in the cases where this information. most of our patients ( %) attended the emergency department of zaghouan with a non-medical transportation. it was a suicide attempt in most cases ( %) and an accidental poisoning in % of patients. the most frequent cause of poisoning in our study was organophosphorus pesticide (n = ; %). the second cause was alpha-chloralose poisoning with seven cases ( %). one patient ingested accidentally an anticoagulant rodenticide. most of patients had ingested (oral route) the rat poison (n = ; %). clinical examination found normal vital signs in ten cases ( %). nine patients ( %) had a shock, eight patients ( %) had an acute metabolic disorder and five patients ( %) had acute respiratory failure or were comatose. all patients enrolled in the study were admitted in the icu for a period of clinical observation of h. stomach pumping (gastric lavage) was performed in patients ( %). an antidote which was atropine was needed in twelve patients. three patients ( %) who ingested alpha-chloralose needed intubation and mechanical ventilation. all patients had a good outcome and were discharged from icu and from hospital. the mean icu length of stay was ± days. conclusion this is the first study of acute poisoning with rodenticides admitted in the new icu. the results of our study were similar to those published in recent literature. cases of acute poisoning with rodenticides reported in this work were not severe. none. introduction the systemic arterial load imposed to the left ventricle (lv) is a major determinant of normal/abnormal cardiovascular function. the lv mean ejection pressure (lvmep) is the best estimate of load faced by the lv throughout ejection. the contribution of the steady and pulsatile blood pressure (bp) component of arterial load to lvmep is debated. we studied the hemodynamic correlates of lvmep using carotid tonometry. intensive care unit patients equipped with an indwelling catheter were studied, thus allowing precise calibration of the tonometer. patients and methods carotid tonometry (complior analyse ® alam medical, france) was prospectively performed on hemodynamically stable, spontaneously breathing patients ( f, mean age ± sd = ± years). carotid waveforms were calibrated from diastolic bp and time-averaged mean bp invasively obtained at the radial (n = ) and femoral (n = ) artery. all patients were free of aortic stenosis. lvmep was the area under the systolic part of the carotid pressure waveform divided by ejection time. results lvmep ( ± mmhg) was strongly related to central systolic bp ( ± mmhg; r = . ) and was also related to mean bp (r = . ), peripheral systolic bp (r = . ), peripheral (r = . ) and central (r = . ) pulse pressure (each p < . ). the lvemp was not related to age, heart rate and stroke volume. systolic pulse wave amplification ratio from carotid to periphery was . ± . . conclusion lvmep was most strongly related to central systolic bp, which combines the influences of the steady and pulsatile components of central arterial load (r = . ). lvmep was less strongly related to peripheral systolic bp, which may be less informative given variable systolic pulse wave amplification across patients. introduction myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to %. many pathological findings were found in the sepsis induced cardiomyopathy including myocardial ischemia, alterations in microcirculation and proinflammatory cytokines. the aim of this study was to assess the prognostic value of a recently developed highly sensitive cardiac troponin i (hstni) assay in patients with septic shock. we performed a prospective observational study in septic shock icu patients within h of admission. exclusion criteria were age > years; pregnancy; post-cardiac arrest and braindead. hstni was measured soon after admission and , , and h after. patients were subjected to transthoracic echocardiography (tte) at study inclusion and regular biochemical and hemodynamic assessments were performed. pearson's chi square and fisher's exact tests were used. p < . was considered significant. conclusion circulating hs-ctni is present in patients with septic shock. a rise of hstni may be an indicator of poor outcome. also, right heart functional abnormalities exist in patients with septic shock. none. evolution of the right distribution width as a pronostic marker during the differents state of shock introduction right distribution width (rdw) has been recently proposed as a pronostic factor in different pathologic situations and especially to the septic patients who stay in icu. some works substantiate the relationship between an alteration of the red blood cell rheology during the septic shock and a severe state of the disease. no one has studied the rdw between the differents shocks yet. we are going to determinate the relationship between rdw and apache ii score, mortality rate in the intensive care unit (icu), at the hospital, at the day and . we investigated those parameters near patients who were admitted at the icu and needed norepinephrine between the first of march and the st of december. they were stratified in différent groups: septic shock n = , cardiogenic shock n = , hemorragic shock n = and obstructive shock n = . results we did not observe any correlation between the rdw and the icu mortality, hospital mortality and at the day and . only a poor significant correlation has been found between the cardiogenic shock and the mortality rate: at the hospital (p = . ), at day (p = . ) and at the day (p = . ) but not in the icu (p = . ). the receiver operating characteristics (roc) curves do not show significant differences between rdw, apache ii score and icu mortality rate or intra hospital. the sample of the hemorrhagic shock and obstructive shock was not usable for this calculation. compared to other studies which were focused on the septic shock where the mortality was approximately %, we determinated a mortality rate near %. conclusion the delta of the rdw d /d did not present any correlation with the mortality rate. in our study, the rdw in the different kind of shocks do not look like to be a good predictive marker of the mortality, except for the patients included in the cardiogenic shock where a poor significant correlation could be highlighted. conclusion cardiogenic shock was the most frequent complication of ami who led to icu admission, whereas mechanical complications are rare at the era of early coronary reperfusion strategies. in addition to severity score, serum creatinine and cardiogenic shock appeared as independent factors of hospital death. none. introduction pulmonary embolism (pe) in high-risk is a partial or total obliteration of the pulmonary arterial network by a fibrin-clot cruoric more than %, the management requires a rapid reduction of pulmonary arterial resistance and right ventricular post load through rapid revascularization by thrombolysis. our aim is to determine the value of thrombolysis in pulmonary embolism and describe the clinical, paraclinical and outcome pulmonary embolism at high risk. patients and methods this is a descriptive study of cases of pulmonary embolism at high risk admitted to the cardiology department to chu oran between and . signs of gravity of (pe) comprising: syncope, circulatory collapse, cardiogenic shock or acute pulmonary sonographic sign of heart. it was confirmed in chest ct. all patients received thrombolysis using the protocol accelerated by two types of molecules: streptokinase or actilyse. the sex ratio was . ; mean age years, ranging from to years; risk factors were dominated by contraception was % and the postoperative % the clinical picture was dominated by cardiogenic shock in % of cases. % cardiovascular collapse and syncope in %; doppler echo all patients had signs of dysfunction of the right ventricle represented by the dilatation of the right cavities and pulmonary hypertension. the cta found a (pe) bilateral in % right in %. thrombolysis using actilyse in patients and streptokinase in cases. the outcome was favorable in patients; with two cases that are complicated by chronic pulmonary heart and the death of patients with cancer. discussion the female predominance is explained by the increase of risk factors hormonal contraception, whose first generation combination hormonal. our patient had a high probability with clinical signs of severity based on the score wells [ ] . this diagnosis was confirmed by chest ct; which shows the vascular bed obstruction degree with a very good sensitivity and specificity. the suspect patients with severe pe and that presented signs of acute pulmonary heart ultrasound have effectively (pe). the indication of thrombolysis was chosen on hemodynamic criteria; success is found in % of patients with improved hemodynamics dice the early hours. this success is explained by the role of thrombolytic in lysis clot to obtain pulmonary arterial revascularization; and reduce pulmonary arterial resistance and the right ventricular afterload which accelerates the healing of right heart failure and improvement of pulmonary capillary volume. the cases who developed a chronic pulmonary heart; it was done immediately a right ventricular dysfunction with pulmonary arterial outset of very high pressures suggestive that the embolism occurred on an already pathological right heart. no cases of massive bleeding were noted in our series. conclusion severe pulmonary embolism is burdened with high mortality; diagnosis is based on the stratification of risk score, was facilitated by the non-invasive strategies that articlent around the doppler echocardiography and ct angiography; thrombolysis can reduce the high mortality related to severe pulmonary embolism. introduction hypertension is a frequent motif for admission to emergencies. the diabetic is increasingly exposed to this risk [ ] . the objective of this study is to evaluate the proportion of diabetic patients presenting to the emergency department with high blood pressure (bp) and to identify their epidemiological and clinical characteristics. introduction sepsis associated liver dysfunction (sld) is usually attributed to systemic and/or microcirculatory disturbance. hypoxic hepatitis, also known as shock liver or ischemic hepatitis, is a life threatening event associated with high morbidity and mortality. doppler ultrasonography is a non invasive method to measure doppler hepatic hemodynamic parameters. the primary objective of this study was to assess the accuracy of the hepatic hemodynamic parameters (portal venous blood flow pvbf and resistance index of the hepatic artery hari) in predicting sld in septic shock patients. the secondary aims were to identify factors associated with sld, investigate the effects of volume expansion (ve) on systemic and intrahepatic hemodynamics and to assess the intra-and interoperator reproducibility. we also analyzed -day mortality. in a prospective design, we included consecutive patients with septic shock ( males; median age: . years) admitted to the icu with septic shock in charles nicolle hospital of tunis from february to july . all patients were resuscitated following the surviving sepsis campaign guidelines. we measured systemic hemodynamic variables (mean arterial pressure (map), and cardiac index (ci)) and performed hepatic doppler before and after volume expansion. we measured pvbf and computed the hari. we recorded the liver function tests (alt, ast and bilirubin) for h. sld was defined as an increase in serum bilirubin ≥ µmol/l (hepatic sofa ≥ ). accuracy of the hepatic hemodynamic parameters to predict sld was measured by the area under the roc curve. p < . was taken to indicate statistical significance. the median sofa score at t was points and the median igs score was points. the sources of infection were as follows: the lungs (n = ), the abdomen (n = ) and the urinary tract (n = ). the incidence of sld in our cohort was . % (n = ). there was no significant difference between "sld group" and "no-sld group" in all hepatic hemodynamic parameters especially the pvbf and the hari. lactate levels were significantly higher in patients with sld (median . vs. . mmol/l). similarly, the platelet count was significantly lower in the "sld group" [mean (± sd) . ± . ( /l) vs. . ± . ( /l); p = . ]. there was no difference in duration of mechanical ventilation, icu length of stay and -day mortality between the groups. the pvbf was significantly lower in patients who died before d (median: vs. l/min in the survivors; p = . ). volume expansion caused a significant increase in ci, mean hepatic artery velocity and the pvbf. the intra-and interoperator reproducibility was good to excellent for the systolic and mean velocities of the hepatic artery, portal vein diameter and the pvbf. conclusion our results don't support the hypothesis that the hepatic sonography is predictive of sld in septic shock. our pilot study showed higher lactate levels and hematologic sofa in sld group. the pvbf was significantly lower in patients who died before d . more experience will be necessary to define the ultimate role of doppler ultrasonography in the evaluation of hepatic perfusion in patients with septic shock. introduction early surgery is the current trend for management of patients with valvular disease. that said many of them, particularly from developing countries, are still operated at a very advanced stage of disease. despite improvements in myocardial protection and surgical techniques, postoperative care after multiple valve surgery (mvs) for advanced rheumatic heart disease (rhd) remains to be a clinical challenge. we conducted a study to determine postoperative complications and morbidity-mortality risk factors in this subgroup of patients. results sixty-two patients were included: with out-of-hospital refractory cardiac arrest and with in-hospital refractory arrest. the initial rhythms was shockable rhythm in ( %) cases. at ecls initiation, the mean no flow was . ± . min and mean low flow (time between the time of refractory cardiac arrest and time at which an ecls flow was provided) was ± min. the mean ecls flow rate was . ± . l/min. initial blood test results were: arterial ph = . ± . and plasma lactate = . ± . mmol/l. eleven ( %) patients survived ( / ( %) acute coronary syndrome, / ( %) severe poisoning due to drug intoxication, / ( %) dilated cardiomyopathy, and / ( %) others). survival was lower for patients with out-of-hospital refractory cardiac arrest, of ( %), than for patients with in-hospital refractory cardiac arrest, of ( %), respectively, p = . . as expected, out-of-hospital refractory cardiac arrest was associated with a more prolonged low flow ( ± min vs ± min, p < . ) and a more profound acidosis (ph . ± . vs . ± . , p = . and arterial lactate . ± . vs ± , p = . ). in univariate analysis, survival was lower for patient with refractory cardiac arrest unrelated to drug intoxication, vs %, respectively, p = . . in addition, mortality was associated with arterial ph ( . ± . vs . ± . , p = . ) and low flow ( ± vs ± min, p = . conclusion in a highly selected group of critically ill patients with refractory cardiac arrest, the potential beneficial effect of ecls could be due only to its clinical impact on reversible causes of circulatory failure (i.e. severe drug intoxication in our cohort). further studies are needed to clarify whether the use of ecls could be considered as a disproportionate tool, specifically in patients with out-of-hospital refractory cardiac arrest due to acute coronary syndrome or associated with prolonged low flow or a profound acidosis. none. post-cardiac arrest shock treated with veno-arterial extracorporeal membrane oxygenation: an observational study and propensity-score analysis wulfran bougouin , nadia aissaoui , alain combes average time between introduction and removed of the ecd was h ( - ). among the esogastroduodenoscopy performed, ( %) were strictly normal. endoscopy showed minor gastric injuries in patients ( %). within these patients, ( %) also presented minor esophageal injuries. esogastric injuries characteristics were mostly similar to usual orogastric probe injuries. one patient ( %) experienced a serious ulcerous esophagitis mimicking a peptic esophagitis, not firmly related to the ecd. no patients necessitated hemostatic local procedure and no significant gastrointestinal bleeding was observed. eight patients ( %) were alive at d , including patients ( %) with a cerebral performance category score of . this compares favorably to outcomes from previous studies. conclusion ecd seems an interesting and safe semi-invasive method of cooling in ohca patients treated with °c-ttm. although it seems slower than more invasive devices to reach °c, ecd was able to strictly maintained the tt within the maintenance phase of ttm. further studies will be necessary to define the exact place of this new device within the cooling strategy in patients necessitating a precise ttm-strategy. none. fig. see text for description introduction since post-cardiac arrest care might influence the outcome, characteristics of receiving hospitals should be integrated in survival evaluation of patients transported in hospital. we aimed at assessing the influence of care level center on survival at discharge in a regional registry of out-of-hospital cardiac arrest (ohca). we prospectively collected utstein and in-hospital data for all non-traumatic ohca patients, in whom a successful return of spontaneous circulation (rosc) had been obtained, from a large metropolitan area (great paris). receiving hospitals were categorized in groups (a, b, c) depending on their respective characteristics (annual volumes, / catheterization availability and temperature management use). we compared patients' characteristics in the groups and performed a multivariable logistic regression using discharge survival at endpoint. results during the study period (may -dec ), patients were admitted in hospitals ( in group a, in group b and in group c). overall survival rate at discharge was / ( %). patients' baseline characteristics significantly differed, as hospitals from group a treated younger patients and more frequent shockable rhythms (p < . ). unadjusted survival rate differed significantly among the groups of hospitals (respectively , and . % for a, b, c, p < . ). however in multivariable analysis, the category of hospital was no longer associated with survival. conclusion in this population-based study, characteristics of receiving hospitals are not associated with survival rate at discharge. this could result from the strategy used for triage, which aims in matching patients' characteristics and resources. introduction acute kidney injury (aki) commonly occurs after cardiac arrest and is associated with an increased mortality and a delayed awaking. early recognition of aki remains challenging, given that serum creatinine increases belatedly after aggression. introduction out-of-hospital cardiac arrests (ohca) are an absolute urgency and have a very poor prognosis. pediatric guidelines differ from adult guidelines for cardiac arrest management. since , adult guidelines apply from the onset of puberty. the main objective was to describe the epidemiological characteristics and outcome of ohca victims while taking puberty into account. the secondary objective was to determine the prognostic factors for survival at d . materials and methods all patients less than years of age, victims of ohca between july , and september , care by a mobile emergency and resuscitation service (smur) participating in french national cardiac arrest registry (réac) were included. patients were split into groups: prepubescent patients (named "children": girls - years, boys - years), pubescent patients (named "adolescents": girls from to years and boys from to years) and "adults" (men and women - years). the "adolescents" group was consecutively compared to the "children" group and to the "adults" group. results children, adolescents and , adults under the age of have been included. ohca in adolescents occurred more often on public roads ( %) or in public places ( %) and were more often traumatic ( %) than those in children and adults. respiratory causes were more frequent in children ( %) than in adolescents ( %) and adults patients ( %). the proportion of shockable rhythm increased with age ( , and % for children, adolescents and adults respectively). survival at d was greater in adolescents ( %) than in children ( %) and adults ( %) (p = . and p = . respectively). in the studied groups, initial shockable rhythm was a survival factor at d (respectively or [ . - . ] for children, adolescents and adults). other risk factors are described in table . conclusion adolescents had better survival at d than the others groups. adolescents and adults had shockable rhythm more often than children. moreover, respiratory failure was less frequent in adolescent and adults patients compared to children. puberty seems to be a good limit to differentiate pediatric patients with ohca. none. introduction non-invasive ventilation (niv) is an effective alternative to endotracheal mechanical ventilation (mv) in the management of acute respiratory failure (arf) patients. nevertheless, it can be still difficult to assess its real feasibility, application and outcome in daily clinical practice. therefore, we report our clinical experience with routine use of niv since the last national recommendations ( ). our aims were to evaluate the clinical efficacy and outcome of niv, and to identify predictive factors for niv failure based on a daily use. patients and methods we conducted an observational retrospective single-center cohort study by reviewing all medical records from january to december in our -bed medical intensive care unit (icu). eligible patients were those having received niv during their icu stay. two groups were defined according to the indication of niv: niv for hypoxemic or hypercapnic arf (arf-niv), and niv used in the post-extubation period for weaning, prevention or treatment of post-extubation arf (post-extubation niv).the main evaluation criteria were the incidence of niv use, success/failure rate of niv and risk factors for niv failure in each group. niv failure was defined as the need for stopping niv whatever the reason (intubation, intolerance, death) within days after its initiation. ( ; ), and was longer in the post-extubation niv group ( days ( ; ) ) than in the arf-niv ( days ( ; ) for hypoxemic arf, ( ; ) for hypercapnic) (p < . ). the overall icu mortality was . % ( . % in hypoxemic group, . % in hypercapnic group, and . % in post-extubation niv group) (p = . ). in multivariate analysis, the main risk factors for arf-niv failure were: saps ii on admission (p < . ), absence of cardiologic history (p = . ) and the cause of arf (p = . ) with a higher failure rate for pulmonary infections than acute cardiogenic pulmonary edema (or . , p = . ). for post-extubation niv, the only independent risk factor for failure was normocapnia before niv initiation (p = . ). conclusion our large longitudinal study demonstrates the feasibility and efficacy of niv applied in daily clinical practice. provided it is performed in a suitable environment by an experienced team, niv should be considered as a first-line ventilatory treatment in various etiologies of arf and a very useful ventilatory support in the postextubation period. nevertheless, risk factors for niv failure should be known by icu clinicians, hypoxemic arf remaining the more difficult indication to manage with niv. réanimation médicale, hôpital saint-louis, paris, france; service de biostatistique et information médicale, hôpital saint-louis, paris, france; réanimation, institut paoli-calmettes, marseille, france; réanimation introduction acute respiratory failure (arf) is the leading cause for icu admission in immunocompromised patients. in these patients, oxygenation strategy is of major interest to avoid the need for mechanical ventilation (mv), which is associated with high mortality rates. in that setting, use of non-invasive ventilation (niv) and oxygen therapy with high flow nasal cannula (hfnc) could be interesting alone or in association, but data about initial ventilation strategy in immunocompromised patients are controversial. to assess how initial oxygenation strategy actually influences the risk of mv on the coming day within the three first days of icu stay. the study end-point was the need for mv on the coming day. we restricted analyses to these first three icu days given, based on our own experience, most of mv was expected to occur by then. we performed a post hoc analysis combining three prospective studies of critically ill immunocompromised patients (two randomized control trials, the ivnictus and the minimax studies and one prospective cohort, the trial-oh study). we only considered patients with arf and a delay between icu admission and study inclusion less than h. we excluded patients who required invasive mv within the first day, those with an icu stay less than day and those with acute pulmonary edema diagnosis at icu admission. in order to estimate and compare the causal effect of daily respiratory management strategy on the probability of intubation in the coming day, we computed inverse probability of treatment weights (iptw) using propensity-score, defined as the probability of actual treatment selection conditionally on observed covariates. to handle confounding in such dynamic regimens, we considered marginal structural models (msm), which have been proposed to estimate the causal effect of a time-dependent exposure when time-dependent covariates that can be affected by the previous treatment are present. two treatment exposure models were considered: niv versus oxygen therapy regardless the device (model ) and hfnc alone, niv alone versus niv + hfnc versus standard oxygen therapy alone (model ). results patients were included in the study. in model , there was no difference between niv and oxygen groups on mv whatever the landmark time. in model , while the unweighted or for intubation at day was significantly higher in the niv group (or . , %ci . - . ) and hfnc group (or . , %ci . - . ) than those in the standard oxygen alone group, these differences disappeared in the weighted samples. using msm, no effect of the oxygenation strategy on mv was found, regardless of the oxygenation devices but the landmark time was associated with a reduced occurrence of mv. conclusion we found no evidence of any significant difference from several oxygenation strategies on mechanical ventilation probability during the first days of icu in a large cohort of immunocompromised patients with arf. none. introduction the role of noninvasive ventilation (niv) is debated in the management of patients with acute hypoxemic respiratory failure. a recent study showed that patients treated with high-flow nasal cannulae oxygen therapy (hfnc) had lower intubation and mortality rates than those treated by the association of hfnc with niv ( ). high tidal volumes (vt) delivewred with niv may be associated with an increased risk of intubation ( ) . we aimed to identify risk factors associated to intubation, in hypoxemic patients with acute respiratory failure and especially the role of vt under niv. patients and methods this is an ancillary study from a multicenter, randomized, controlled trial including patients with acute hypoxemic respiratory failure (florali-study). we focused on only patients with moderate or severe hypoxemia (pao :fio ratio ≤ mmhg) and we excluded those with mild hypoxemia. the criteria for intubation were predetermined including worsened or persisted respiratory failure, impairment of neurologic status and hemodynamic instability. results after adjustment on the oxygenation strategy, the two factors independently associated with intubation were the presence of bilateral pulmonary infiltrates at admission (or . simulation conditions enables to reproduce its occurence, using different types of tools, from physiological parameters to heart rate variability and psychocognitive tests. future research is required to evaluate the impact of these parameters on teaching. none. with stratification by centre and operator experience. an only inclusion criterion was: "patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if: contraindication to orotracheal intubation (e.g., unstable spinal lesion); insufficient time to include and randomize the patient (e.g., because of cardiac arrest); age < years; pregnant or breastfeeding woman; correctional facility inmate; patient under guardianship; patient without health insurance; refusal of the patient or next of kin to participate in the study; previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess occurrence of spo < % during intubation procedure between groups of preoxygenation: bvm (at a minimum flow of l/min, niv ( % fio ), hfnc (at a minimum flow of l/min, with % fio ), and nrm (at a minimum flow of l/min). between-groups difference in desaturation occurrence was adjusted for baseline covariates significantly associated with the group membership (p < . ). multivariate analysis of the occurrence of a desaturation (< %) was performed using logistic regression. bag-valve mask was considered reference. results baseline characteristics were showed in table . groups were similar at baseline except for pao /fio ratio. in univariate analysis, age (p = . ), saps (p = . ), pao /fio ratio (p = . ),spo (p = . ) and method of preoxygenation (p = . ) were associated with occurrence of desaturation below %. in multivariate analysis, spo at randomization and method of preoxygenation were only predictors of desaturation below %. bvm and hrm were associated with similar risk of desaturation occurrence whereas niv (or . introduction intubation procedure is a challenging issue in intensive care unit (icu) [ ] . cardiac arrest related to intubation in critically ill adult patients has been poorly studied. the studies were not powered to conclude on this rare outcome [ ] . the main objective of our study was to establish the incidence of cardiac arrest and to assess the risk factors of cardiac arrest in a large prospective database of intubation procedures performed in icu. five prospective studies were included, with similar data collected before, during and after intubation procedures using the same methodology. the primary outcome was the incidence of cardiac arrest related to intubation. the secondary outcomes were the death (cardiac arrest without return of spontaneous circulation (rosc)), the cardiac arrests with rosc, the complications related to intubation, the length of icu stay and the -day mortality. the factors associated with cardiac arrest related to intubation procedures were assessed by univariate and multivariate analysis based on patient, provider and practice characteristics. results among the intubation procedures included, cardiac arrests ( . %) occurred, including with rosc ( . %) and without rosc ( . %). main patient, provider, procedure characteristics and outcomes according to cardiac arrest related to intubation are presented in table . in multivariate analysis, the independent predictors of cardiac arrest related to intubation were low systolic blood pressure prior to intubation, hypoxemia prior to intubation, no preoxygenation, overweight or obesity and age > years. mortality rate at day was significantly lower in patients intubated without cardiac arrest ( . %, of ) than with cardiac arrests overall ( . %, patients of , p < . ) and cardiac arrest with rosc ( %, patients of , p < . ). conclusion cardiac arrest related to intubation in adult icu is not a rare event occurring in . % of cases with high immediate mortality of . % and at day of . %. we identified five independent risk factors to cardiac arrest which of them could be modifiable. optimal preparation to intubation procedure could help to prevent those cardiac arrests. introduction naasotracheal intubation (nti) has been progressively given up in favour of the orotracheal intubation (oti) in intensive care unit (icu). this could be explained by more frequent infectious (sinusitis and ventilator associated pneumonia) and non-infectious (epistaxis, turbinates bones injury) complications the former being thought to be more frequent with nti. however, whereas infectious sinusitis is a risk factor for vap, no study has yet demonstrated that oti decreases the infectious sinusitis rate compared with nti. furthermore, nasal route could improve patient comfort and decrease auto-extubation. finally nti can be performed without laryngoscopy with less risk of lips and dental injury. in this prospective study, we aimed to compare the complication of nti and oti and to assess the comfort of the patient. we performed a prospective observational study in a -bed medical icu including patients requiring endotracheal intubation. the intubation route was let at the discretion of the physician in care of the patient, however oti was compulsory in case of cardiac arrest, severe hypoxemia (p/f < when available) and clotting perturbation. for each patient, age, sex, sapsii, mechanical ventilation duration. intubation route were recorded as well as complications during the placement of endotracheal tube. infectious and non infectious complications during invasive ventilation period were also recorded. in patients who were successfully extubated, pain, burning feeling, dryness and the wish of tube removal were assessed using visual analogic scales (vas conclusion despite its small size, and the absence of randomization, the present study suggests that nasotracheal intubation improves the comfort and the tolerance of tracheal intubation and is not associated to higher rates of vap. none. effect of mode of hydrocortisone administration in patients with septic shock: a prospective randomized trial oussama jaoued , rim gharbi , najla the baseline characteristics of patients were similar between the two groups. sepsis was secondary to community-acquired infection in % of cases. there was no difference in mortality between groups ( % in continuous groups and % in discontinuous group). sofa score was significantly higher at days , and in discontinuous group. length of stay, duration of mechanical ventilation, number of day without vasopressors, and the occurrence of adverse events were similar in the two groups. conclusion the mode of hydrocortisone administration in patients with septic shock has no influence on morbidity or mortality. the occurrence of adverse events was similar. introduction widespread activation of coagulation with platelet consumption is a pathophysiological feature of severe sepsis and septic shock. thrombocytopenia, either defined by platelet count below g/l or by a significant relative - -percent decrease in platelet count is a potent poor prognostic factor in sepsis. besides their role in hemostasis, platelets also carry various immune and inflammatory functions that are likely to impact on host defense against infections. we aimed to assess whether changes in the platelet count induced by sepsis is associated with the development of subsequent nosocomial infections. patients and methods patients were obtained from two prospective studies about immuno monitoring of dendritic cells and innate-like lymphocytes in critically ill septic patients ( , ) . adult patients with severe sepsis and septic shock were included. exclusion criteria were any immunosuppressive condition (hematological malignancy, hiv infection at any stage, bone marrow or solid organ transplantation, daily corticosteroid therapy > . mg/kg prednisone-equivalent, chemotherapy or any other immunosuppressive treatments), pregnancy, do-not-resuscitate orders on admission. in addition patients who died or who received platelet transfusion during the first week after icu admission were also excluded. platelet counts were collected on the day of sepsis diagnosis (d ) and then on d , d and d . the relative variation in platelet count at day n compared to day was calculated as follows: (count at day n − count at day ) × / (count at day between between d and d , between d and d and between d and d were also similar between patients with and without icuacquired infections (fig. ). discussion in this preliminary study from selected cohorts of nonimmunocompromised patients, sepsis resulted in mild alterations in platelet counts, making it unlikely to become associated with the development of nosocomial infections. it would be relevant to address this question in larger cohorts of non-selected patients, as well as the impact of platelet transfusions in this setting. conclusion changes in platelet counts were not associated with an increased susceptibility towards icu-acquired infections in non-immunocompromised patients with severe sepsis and septic shock. introduction sepsis is the leading cause of mortality in the intensive care unit (icu) patients despite the progress regarding their care. the immunodeficiency due to sepsis with the consequent profound lymphocyte alterations is now well proven. the objective of this work was to determine the prognostic impact of lymphocytopenia in septic patients in icu. retrospective study including all patients hospitalized for sepsis or septic shock between / / and / / . the sepsis and septic shock definitions were adjusted with the third international consensus definitions for sepsis and septic shock. were excluded from the study patients of onco-hematology. lymphocytopenia was defined as an absolute lymphocyte count less than level of /mm during the first h of hospitalization. the prognostic factors analyzed for the lymphopenic and non lymphopenic patients were in hospital mortality, the occurrence of nosocomial infections and hospital length of stay. results among the patients, aged ± years, patients were with septic shock and patients with sepsis. igsii score and sofa score were respectively ± and ± . four patients were immunocompromised due to hiv infection in one case and an immunosuppressive therapy in cases. lymphocytopenia was observed in patients ( %). twenty-eight patients ( %) died within an average of ± days. it was noted the occurrence of nosocomial infections. the median length of stay was days with extremes of one and days. the lymphopenic patients were comparable to non lymphopenic patients in terms of medical history and severity scores. mortality was comparable between the groups with a rate of % (n = ) in lymphopenic patients and % (n = ) in non-lymphopenic patients (p = . ). the earliness of death was correlated with the duration of lymphopenia (r = . , p = . ). the occurrence of nosocomial infections was not different between the two groups: % (n = ) for lymphopenic and % (n = ) for non lymphopenic patients. the hospital length of stay was not different between the two groups but was correlated with the duration of lymphocytopenia (r = . , p = . ). conclusion lymphocytopenia is frequently found in sepsis. lymphocytopenia was not associated with excess of mortality nor with the subsequent occurrence of infectious complications during the icu stay. his persistence was associated with an earlier death and a more prolonged hospitalization. none. introduction relative adrenal insufficiency (rai) is common in icu patients, particularly during septic shock ( ). it has been shown that the rai also occurs during cardiogenic shock ( ) . septic cardiomyopathy occurs in a significant proportion of septic shock patients. the aim of this study was to evaluate the role of rai on septic cardiomyopathy. patients and methods prospective observational study conducted in the intensive care in one university hospital in france. patients meeting the criteria for septic shock without prior corticosteroid therapy and without chronic heart disease were included. total blood cortisol levels were assessed immediately before (t ) a short corticotropin stimulation test ( . mg iv of tetracosactrin) and and min afterward. Δmax was defined as the difference between the maximal value after the test and t . rai was defined as an inappropriate adrenal response with Δmax < µg/dl and septic cardiomyopathy as the appearance of cardiac systolic dysfunction (left ventricle ejection fraction < %) within the first days of septic shock. we performed a multivariable analysis using backward stepwise logistic regression to identify independent predictors of septic cardiomyopathy. discussion although the definition of rai is not consensual, a threshold of Δmax at µg/dl has been widely used in septic shock, with or without the use of t ( ). the usefulness of substitutive doses of steroids in septic shock is controversial, but many authors assume this treatment has a potential in reversing overt vasoplegia. our data suggest an implication of rai in septic cardiomyopathy. conclusion we found rai to be an independent predictor of septic cardiomyopathy. these findings may suggest a new role for substitutive doses of steroids in the hemodynamic management of septic shock. introduction regional perfusion parameters, like lactate, pyruvate and glycerol, may predict outcome in septic shock patients. continuous venovenous haemofiltration (cvvh) has been considered beneficial in septic shock patients. the aim of our study was to investigate whether cvvh, in comparison to intermittent haemodialysis (ihd), is able to improve regional perfusion in septic shock patients studied by muscle microdialysis. patients and methods it was a prospective, randomized, clinical study, including septic shock patients with acute renal failure, aged over years. patients were randomized to receive either cvvh (n = ) or ihd (n = ) for renal replacement therapy. intermittent haemodialysis was carried out during the first h of the h study period. systemic haemodynamics and interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were obtained at baseline, , , and h after initiation of renal replacement by using muscle microdialysis. results regarding systemic haemodynamics parameters, cvvh caused a decrease in heart rate in contrast to ihd after h (− ± vs + ± /mn). there were no changes in vasopressor support throughout the -h study period and so systolic blood pressure remained stable in both groups. during the h of all renal replacement therapies there was no significant change in muscle pyruvate and glucose levels. during cvvh muscle lactate decreased constantly, as did muscle glycerol levels. this decrease reaches a significant levels at h for muscle lactate and at h for muscle glycerol (fig. ) . conclusion our results suggest that among septic shok patients, cvvh may improves regional perfusion in comparison with ihd. none. introduction acquired hypernatremia (h-na) is an independent risk of death among icu patients ( ). in the rct "hyper s" study, we compared normal to % hypertonic saline during the first h in patients with septic shock with normal serum na concentration (sna) at baseline. the study was prematurely stopped for potential harmful effect associated with more frequent h-na. we assessed the role of h-na on mortality. patients and methods data are a post hoc analysis of the "hyper s" study database including patients. sna was measured at h , every h for days and then daily until d . study fluids were stopped if sna > or > mmol/l increase over h. mild, moderate, and severe h-na were defined as sna > mmol/l, > mmol/l and > mmol/l, respectively. sna profiles were compared between d survivors and non-survivors. acute kidney injury (aki) was defined by doubling serum creatinine and/or need for dialysis. results patients with available data were analysed. ( %) developed h-na (mild: %, moderate: %, severe: %). no matter the absence or presence and its severity, h-na did not affect mortality ( , , , and %, respectively without, with mild, moderate, and severe h-na, p = . ). sna profiles were similar between survivors and non-survivors (table ) . a sensitivity analysis performed among survivors at d did not change the results. compared to patients without h-na, aki occurred in % of patients with h-n vs % (p = . ), atelectasis in versus % (p = . ) and icu acquired weakness in versus % (p = . ). conclusion hypernatremia occurrence is not associated with an increased risk of morbidity and mortality during hypertonic fluid resuscitation in septic shock. none. introduction guidelines about the moderate hypokalemia treatment (between . mmol/l and . mmol/l) are based on experts estimations, and non-specific ones for patients in the intensive care units (icu). the aim of this study was to evaluate the correction of the hypokalemia in an icu and the compliance of recommendations. materials and methods an observational epidemiological, retrospective and monocentric trial has been realized during a period of months (from january to february ). the study population included hospitalized patients in the icu who have shown a first moderate hypokalemia episode, all cause considered. patients who have presented an acute renal failure with a kdigo (kidney disease: improving global outcomes) score of three the day of their inclusion were excluded. the main primary study endpoint was percent correction of the serum potassium after h. the secondary study endpoints were the incidence rate of moderate hypokalemia and the efficacy about the hypokalemia correction in accordance with the achieved treatment consistent or not with recommendations. results patients had at least one episode of hypokalemia. the incidence rate of the hypokalemia first episode was . %. the study population included patients. igs score was . (± ). patients required mechanical ventilation at the inclusion. the serum potassium was greater than or equal to . mmol/l after h about patients ( . %) (corrected group). at h one patient had a serum potassium higher than mmol/l. the average total potassium was respectively . infusion of potassium and ( . %) patients have been a management compatible with the most common recommendations (input potassium chloride of mmol, use of the enteral administration and lack of continuous intravenous infusion). the percent correction of the hypokalemia after h was respectively of / ( . %) in the group in which recommendations had been respected and of / ( . %) in the other one (p = . ). discussion in our knowledge there are no previous studies that have specifically focused on the correction of the moderate hypokalemia in critically ill patients. in our study the incidence rate of the moderate hypokalemia was lower than data from the literature because we have only considered the first episode of the hypokalemia [ ] . among patients without contraindication to the enteral administration, this one was used in less than half of the cases. % of these patients received potassium with a continuous intravenous infusion and only patients received medical care conform to the guidelines. the medium potassium quantity provided was very lower to the guidelines. only % of the patients have been corrected after h without any difference in the medium potassium quantity which has been provided in relation to the uncorrected group. conclusion only . % of moderate hypokalemia in icu are corrected after h. the intravenous way is considerably used (in % of cases) with a poor return. a wide-ranging study is necessary to determine the best correction modes. none. results patients were included. mean ± sd age was ± years, % were male, mean ± sd saps ii was ± . icu length of stay was ± days and icu mortality rate was %. during the first days in the icu, % of patients received at least one nephrotoxic drug. % of patients received one, % received two, % received three and % received more than three nephrotoxic medications. diuretics, antibiotics and iodinated contrast media were the nephrotoxic drugs most frequently administered to, respectively, , and % of patients. aki (kdigo stage or higher) occurred in % of patients during the first days in icu. the proportion of patients with aki increased with the number of nephrotoxic drugs received: / ( %) of the patients not exposed to nephrotoxic drugs developed aki whereas, respectively, / ( %), / ( %), / ( %) and / ( %) of the patients receiving one, two, three, and more than three nephrotoxic drugs developed aki. the univariate association between the number of nephrotoxic medication and aki persisted in the multivariate analysis adjusted on baseline saps ii score (p < . ). conclusion the significant proportion of patients exposed to nephrotoxic drugs and the observed association with aki warrants further investigation. statistical adjustments for multiple potential confounders is needed in order to assess a potential causal relationship which would lay foundations for interventional studies. none. ( ) the minimal kidney aggression by current monomeric nonionic low-osmolar contrast media, late serum creatinine increase being explained by the occurrence of later (between the th and the nd hour) kidney injury due to critical illness or its therapy or ( ) insufficient sensitivity of early ( h) measurements of this biomarker to detect contrast-associated aki. competing interests partial financial support, no implication in data analysis and interpretation. introduction diabetic ketoacidosis, generally resulting from an absolute deficiency of insulin, is a frequent cause of hospitalization in intensive care unit. recommendations for diagnosis of diabetic ketoacidosis, care and site of admission have been published by the english society of diabetology. icu admission are recommended if one of the following criteria is present: gcs < , systolic arterial pressure (sap) < mmhg, spo < %, ketosis > mmol/l, hco < mmol/l, ph < . , potassium level < . mmol/l or anion gap > mmol/l. however, it is suspected that adhesion to recommendations remains low. in this study, we aimed at describing patients admitted for diabetic ketoacidosis in icu. we looked at adhesion to published recommendations regarding admission and care. we also described metabolic complications and looked for an association between complications and dose of initial insulin therapy. complications hypoglycemia (< . mmol/l) was observed in % of patients within the first h in which % were < . mmol/l. this was and % of patients between and h of icu stay. hypokalemia below . mmol/l happened in % of patients within the first h and in % between and h. neither hypoglycemia nor hypokalemia were correlated with initial insulin bolus or initial dosage of continuous intravenous insulin. hypophosphatemia < . mmol/l was observed in % of patients. discussion in this study, admission to icu was consistent with british recommendations since most patients presented at least one clinical or biological criterion indicating icu admission. arterial blood gas were sampled in the large majority of patients despite consistent data showing that venous blood gas might be sufficient in non-hypoxemic patients. also, initial insulin bolus and sodium bicarbonate perfusion were performed in a significant subset of patients despite absence of convincing data or recommendations supporting their use. finally, significant hypokalemia and hypoglycemia were frequent in these patients. these complications are in theory favored by insulin therapy but we did not observe a correlation between administration of an insulin bolus or the dose of continuous intravenous insulin perfusion. conclusion in this retrospective multicentre study, patients admitted in icu for diabetic ketoacidosis were correctly oriented regarding the british recommendations. metabolic complications (hypoglycemia and hypokalemia) were frequent but not correlated with initial dose of insulin. the appropriate rate for hypernatremia (h-na) correction is unknown. under-correction could be associated with worse outcome. experts recommend a rapid correction of acute (< days) and sever (> mmol/l) h-na with a rate of − mmol/l/h until na < mmol/l ( ). correction should be, therefore, obtained within h. in patients with septic shock resuscitated with iso-or hypertonic saline and who acquired acute severe h-na, we assessed if the correction rate was associated with mortality. patients and methods data are a post hoc analysis of the rct "hyper s" database comparing normal to % saline for h in septic shock. serum na (sna) was measured at h , every h for days and ) . h-na correction rate was more rapid in non-survivors, p = . (table ). over-correction occurred similarly in survivors ( %) and non-survivors ( %). the time to reach sna normalization was shorter in nonsurvivors (p = . ). after adjustment for sapsii and maccabe scores, more rapid correction rate remained significantly associated with mortality: or . ; % ci ( . - . ), p = . . conclusion in the context of acute severe h-na induced by fluid resuscitation, a rapid correction rate might be associated with even aggravated rather than improved mortality. introduction systemic capillary leak syndrome (slcs) is a rare disease characterized by recurrent life-threatening attacks of capillary hyper permeability in the presence of a monoclonal gammopathy (mg). during acute episodes, the leak of fluid and proteins from the intravascular compartment to the interstitium results in clinical signs of both acute hypovolemia and interstitial edema. biological profile is pathognomonic with marked hemoconcentration and paradoxal hypoproteinemia. hypovolemic shock is the classical feature of severe scls attacks. however, beside this typical hemodynamic profile, several case report described myocardial dysfunction during scls attacks. the objectives of this study were to assess frequency, characteristics and outcome of myocardial involvement during severe scls attacks. ( %) mechanical ventilation, ( %) renal replacement therapy, ( %) veno-arterial extracorporeal membrane oxygenation, ( %) intra-aortic balloon pump and ( %) an impella. compartment syndrome occurred in ( %) patients and ( %) died in icu. we then compared the patients with myocardial involvement to the without clinical and biological manifestations were similar in between groups. however, chest pain ( vs %, p = . ), dyspnea ( vs %, p = . ) and respiratory failure ( vs %, p = . ) were more frequent in patients with myocardial involvement than in others. there was no difference between groups regarding treatment received in icu, complication and outcome except for the use of va-ecmo ( . vs %, p = . ). conclusion myocardial involvement seems frequent in patients with severe scls attack, occurring in % of the cases. such patients exhibited classical features of scls attacks. myocardial involvement was responsible for altered lvef or transient ventricular hypertrophy. myocardial dysfunction could be severe, even requiring mechanical circulatory support. scls attacks should be known as a cause of severe reversible myocardial dysfunction and hypertrophy. none. introduction in refractory cardiorespiratory emergencies, ecmo appears a good alternative to conventional treatment. its extracorporeal circuit justifies curative anticoagulation explaining haemorrhagic and thrombotic complications. activated clotting time (act) is empirically and commonly used to assess anticoagulation but with large inter and intraindividual variabilities. in practice, antixa activity dosage is available to approach anticoagulant effect of heparin and is less expensive, but data during ecmo are missing. we sought to demonstrate the lack of correlation between antixa and act in patients under ecmo support. we prospectively include patients supported by ecmo in chu toulouse, france, between / and / for circulatory/respiratory support. anticoagulation was achieved by unfractionated heparin: initial bolus then continuous intravenous infusion ( - iu/h), for antixa target of . - . . concomitant dosing of antixa (laboratory) and act (hemocron ® ) was conducted two times a day on the same sample throughout the ecmo period. relationship between act and antixa was analyzed by spearman correlation (rho). after transformation into categorical variables (obtained target = ; outside the target = ), analyzes were completed by a concordance study (kappa). as recognized on literature act's targets were between and . results patients were included: men ( %), median age yo ( - ). indications were veno-arterial (n = ) and veno-venous ecmo (n = ). ecmo median duration was days (hours to days). spearman correlation test found low and inconsistent correlation between antixa and act (rho spearman < . ). this correlation lack present from the day one, worsens over time. analyzed kappa showed no discrepancy between the areas "targets" of act and antixa confirming the results (table ) . conclusion use of act for ecmo anticoagulation monitoring doesn't seem appropriate and high price probably justifies preferential use of antixa in clinical practice. analyzes of relationships between antixa and bleeding/thrombotic events are needed to confirm the antixa place and its target in these indications. introduction postcardiotomy cardiogenic shock (cs) has an incidence of % to % after routine adult cardiac surgery. in . - . % of cases, an venoarterial extracorporeal life support (va-ecls) is requested. the -month survival rate is . % ( ). survivors may suffer of physical and psychological impairments as well as an alteration of quality of life. this study was designed to assess the outcomes, long-term health- since icu discharge, % of patients reported physical sequelae., ecls-related limb pain occurs in % of patients while paresthesia occurs in % and chronic-tiredness in %. mean karnofsky score was % (table ) . conclusion after va-ecls for postcardiotomy cardiogenic shock longterm physical and psychological sequelae are frequent in survivor discussion interest for fluid management is growing in critical patients. nevertheless, no study has yet investigated its impact in selected patients with cardiogenic shock treated with va ecmo. our study suggested a possible association between fluid overload and mortality but lack the power to confirm these results with multivariate analysis. conclusion fluid management is a key therapy during va ecmo but fluid overload could be associated with worsen outcomes. further studies with larger population are warranted before considering fluid restriction trials. introduction extracorporeal life support (ecls) has taken an important place in the treatment of cardiogenic shock (cs) or refractory cardiac arrest (ca). however, ecls deplore a high mortality rate in the first days raising important ethic and economic consequences. in this context, continuation of support should be reassessed precociously. the aim of this study was the research of prognostic factors of -days mortality, h after ecls implantation for cs or ca. materials and methods all patients undergoing ecls in our tertiary center during a -year period were prospectively included. the ecls were managed with a multidisciplinary protocol based on consensus. clinico-biological data were collected just before and h after ecls implantation. these data were compared between survivors and deceased at month. , cpc score was respectively for patients, for , for . at months, cpc score changed only for the patients with a cpc score at (one died after another suicide attempt, one changed his cpc score to ). in the group without ca (n = ), had normal neurological status at months and at months (one patient died because of a cancer). among these patients, % returned at home and % returned to work. ( %) patients re-attempted suicide in the year. the major risk factor of mortality is the presence of a cardiac arrest on hanging site. all the other factors found to be related to mortality are well known risk factors in cardiac arrest of other origin. in univariate analysis, risk factors of neurological sequelae at months were a cardiac arrest on hanging site (p = . ) an elevated diastolic blood pressure ( vs mmhg; p = . ), a lower initial glasgow score ( vs ; p = . ), and an elevated blood glucose ( . vs . g/l p < . ) at admission in icu. discussion our cohort of self-hanging patients can be divided in two parts: a) patients with ca in the pre-hospital period with a high mortality and a good neurological recovery in / surviving patient, but with a small group; b) patients without ca with a very low mortality and a very good neurological recovery. these results seem to be better than in the most important cohort [ ] published until now in self-hanging patients without ca and not treated by hbot (mortality at . % and . % of poor neurological recovery). conclusion patients surviving a self-attempted hanging who have not presented ca and treated by hbot have mainly a good neurological outcome. randomized control study should be undertaken to confirm hbot effectiveness in that indication. introduction venoarterial extracorporeal membrane oxygenation (va-ecmo) is increasingly used to treat refractory cardiogenic shock or cardiac arrest. acute brain injury (i.e. ischemic stroke, haemorrhage and/or failure to awaken because of diffuse brain injury) may occur in up to % of patients on va-ecmo and is associated with increased mortality and poor functional outcome in survivors. however, early indicators of neurological outcome are lacking in this population. we aimed to assess the prognostic value of early electroencephalography (eeg) alterations during va-ecmo. we conducted a prospective single-center study in the medical icu of a university hospital on consecutive patients cannulated to va-ecmo. a standardized clinical neurological evaluation including the rass score, the gcs score, the full outline of unresponsiveness (four) score and brainstem reflexes was coupled to an intermittent eeg. eeg was recorded as soon as possible within the first h after va-ecmo cannulation. eeg characteristics were analyzed by a neurophysiologist who was blinded to the patient's condition. a severely altered eeg pattern was defined as a predominant delta frequency, discontinuous, unreactive and/or an isoelectric background. the primary endpoint was poor neurological outcome, defined as the composite of death or acute brain injury on neuroimaging within days. data are presented as median (interquartile range) or number (percentage). false-positive rates (fprs, corresponding to -specificity) of poor neurological outcome were calculated for each significant predictor, using an exact binomial % confidence interval (ci). results sixty-nine (age ( - ) years) patients with a sofa score of ( - ) were included. main indications for ecmo were: post cardiac surgery (n = , %), terminal dilated cardiomyopathy (n = , %), and acute myocardial infarction (n = , %). cardiac arrest before ecmo cannulation was noted in ( %) patients. eeg was recorded ( - ) days after va-ecmo cannulation and ( %) patients were sedated at time of eeg. at day , ( %) had a poor outcome (n = deaths and n = patients alive with acute brain injury). in univariate analysis, a lower rass score (p = . ), a lower four score (p = . ), a lower score on the motor component of the glasgow coma scale (p = . ), and a lack of cough reflex (p = . ) at the time of eeg were significantly associated with a poor outcome. a severely impaired eeg pattern or presence of a discontinuous background activity were also associated with a poor outcome (p = . and p = . , respectively). indicators of poor neurologic outcome are presented in the table . among all parameters, a discontinuous background activity was the only variable that constantly predicted poor outcome (false-positive poor outcome prediction rate of %, % ci - %). conclusion early intermittent eeg has a strong prognostic value for sedated patients on va-ecmo. presence of a discontinuous eeg background activity seems to be more accurate than clinical alterations to predict a bad neurologic outcome at days. none. table ). it was not found a significant association of ctp to mortality ( % in the case group and % in control group, p = . ). other factors that increased mortality were coma, seizures, shock, oedema, cellularity in csf > units/mm . otherwise, the ventilation length was prolonged with ctp group ( . vs . days, p = . ) and neurological sequels namely the epilepsy was more frequent with the group ctp: ( vs %, p = . ). conclusion the occurrence of ctp on bacterial meningitis was significantly associated with ct scan lesions which seems to be an association be in both directions. also, the positive culture predisposed more to the ctp. mortality was higher with the presence of ctp but without real significance. the ctp was a factor that extends the ventilation time and exposed to the post infectious epilepsy. introduction acute bacterial meningitis requires rapid triage and therapeutic decision-making. the aim of this study was to assess the overall ability of a point-of-care glucometer to determine bacterial infection in cerebrospinal fluid (csf). we performed a prospective, observational study. we included patients for whom an analysis of csf was indicated by the physician in charge with blood sampling performed for glucose concentration measurement within h. we simultaneously measured the glucose concentrations in csf and blood using a central laboratory and point-of-care glucometer. the diagnosis of bacterial meningitis was determined by two physicians after reviewing the complete medical chart. we compared csf and blood glucose concentrations and csf/blood glucose ratios obtained at the bed-side with a glucometer versus those obtained by the central laboratory. we determined the performance characteristics of the csf/blood glucose ratio provided by a glucometer to detect bacterial infection in the csf immediately after csf sampling. conclusion we demonstrated that the csf/blood glucose ratio measured by a glucometer can serve as a clinical decision support tool for the early detection of csf with a high probability of bacterial infection. this costless point-of-care method has the potential to expedite medical decision-making for the triage of adult patients with suspected meningitis in the emergency department immediately after lumbar puncture. none. introduction cardiac arrest remains a frequent cause of admission in intensive care unit. a majority of patients will die during their hospital stay mainly from consequences of hypoxic-ischemic brain injury after a decision of withdrawal of life sustaining therapy support by a prediction of poor outcome. the reliability of prognostication is crucial, but is still a difficult and uncertain exercise. eeg is the most widely used prognostic tool to support a clinical examination and is accessible in most hospitals. it is recommended for both prognostication and ruling out subclinical seizures. there is no high-level evidence for predicting poor prognosis using eeg because of the wide variety of classification systems used and the interrater variability. our objective is to assess the prognostic value of simple eeg features based on the recent american clinical neurophysiology society (acns) standardized classification and to study the interrater variability. we conducted a retrospective monocentric observational study in a bed medical intensive care unit of the university hospital la timone, marseille, france. all patients aged of more than year-old admitted for a resuscitated cardiac arrest between november and july who underwent therapeutic hypothermia and a full multimodal prognostic evaluation including a eeg were included in the study. outcome was classified according to the cerebral performance category score measured at day . unfavorable outcome was defined as death (cpc ), persistent vegetative state (cpc ), or severe neurological disability (cpc ). favorable outcome was defined as moderate neurological disability (cpc ), or no disability (cpc ). eeg was performed in all patients still comatose after rewarming between and h after admission and after discontinuation of sedation. eeg interpretation was made by independent senior neurophysiologists, blind to the outcome. eeg features are based on the latest acns classification. for each eeg feature, sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv) for predicting an unfavorable outcome were calculated. results during the study period, cardiac arrest were admitted of which patients went through a full neurologic evaluation and were finally included in the study. according to neurological outcome, % had a favorable evolution, and % had an unfavorable outcome. the presence of burst suppression, and epileptiform activity was constantly associated with an unfavorable prognostic with a % specificity and % false positive. a non-reactive eeg is strongly associated with an unfavorable evolution with a % specificity and % false positive. other features including periodic or rhythmic patterns and low voltage were inconstantly associated with unfavorable outcome. kappa score for all eeg feature was slight or fair and always under . . discussion this study allowed us to identify a homogenous cohort of comatose patient after cardiac arrest who underwent therapeutic hypothermia. we identified simple eeg features based on the new classification of the acns constantly associated with unfavorable outcome. these features must be known by intensivists to better integrate eeg in the multimodal evaluation of neurological prognostic. there is important interrater variability that must lead to caution and to always use multimodal approach to prognostic an unfavorable outcome. conclusion bedside eeg is an excellent tool for predicting outcome of post-anoxic coma through simple eeg features. burst suppression, epileptiform activity and non-reactive eeg are strongly associated to neurological outcome after cardiac arrest. however, the interrater variability emphasize the need of being well trained for the standardized methods of evaluating eeg parameters. introduction emergent reintubation is a well-known risk of laryngotracheal trauma and of ventilatory acquired pneumonia. to precisely define its risk before extubation for each patient is a part of quality of care in intensive care units. none of these consecutive children representative of picu activity has been reintubated. the coming prospective muticentric study which aims to validate alt in childhood must precisely define this criteria of evaluation. conclusion the different methods of alt are feasible in real clinical conditions in picu. because of the increasing use of cuffed etts in a wide variation of patients with different body weight, the best alt to use at the bedside must be definitively validated in this population. introduction prolonged mechanical ventilation (pmv) and chronic mechanical ventilation (cmv) in neonates is associated with a high morbidity and mortality. the objective of the study is to identify, among the patients with pmv, those that evolved to cmv, as well as the adverse respiratory, neurological and feeding sequelae. we conducted a retrospective study of the last years at the chu sainte-justine (montreal, canada). chart review included patients with pmv (≥ days) using the paediatric definition adapted from the namdrc consensus conference ( ) . demographic and clinical data, including follow-up at and months corrected age, was collected for each included patient. the evolution of pmv neonates with cmv (≥ days) and without ( - days) was compared. we identified neonates that met criteria for pmv. patients born between and (n = , % of the cohort) were analyzed. around half of the patients ( - patients a year) are transferred from the neonatal unit to the paediatric intensive care unit. in our center, they represent around % of total admissions, but their length of stay is among the longest. among these newborns, % were preterm (n = ) with % (n = ) born before weeks gestation. of all patients with a malformation ( %, n = ), had a thoracoabdominal anomaly and had congenital heart disease. thirty-six patients had cmv with mean ventilation time of days (range - days). survival at months corrected age was % ( / ) in the pmv group and % ( / ) in the cmv group. at months corrected age, % of patients were dependent on artificial enteral feeding (nasogastric tube or gastrostomy), with % in the pmv group and % in the cmv group. nine percent of patients had oxygen supplementation ( patients in the pmv group and in the cmv group), and % were mechanically ventilated. ten percent of patients had a tracheostomy ( patients in the pmv group and in the cmv group). discussion neonates with cmv have more sequelae. their rapid identification (at days of ventilation) is essential to implement multidisciplinary development care in order to minimize neurodevelopment impairment. conclusion most newborns in our pmv cohort have a congenital malformation. survival at months corrected age appears equivalent in both pmv and cmv group. artificial enteral feeding is more frequent in the cmv group and most patients have no respiratory support at months corrected age. none. the value of pressures and volumes in assessing the fluid responsiveness depend on the systolic cardiac function in adult ( ). we have studied the relative value of static filling volume and pressure to predict the fluid responsiveness, according to systolic cardiac function in children during acute circulatory failure. patients and methods patients under years old with an acute circulatory failure of two intensive care units during a year period of inclusion were analyzed. an exhaustive cardiac echography was performed initially (indexed end-diastolic volume (edvi) and e/e' from transmitral and tissue doppler were recorded), and the stroke volume index (svi) was measured before and after a fluid challenge (a ml/ kg of crystalloid over min results twenty-five children with acute circulatory failure were included. fluid responsiveness occurred in of the fluid loading events with low lvef, and in of the fluid loading events with normal lvef. pressure approach: for low and normal lvef, the auc-roc for fluid responsiveness was respectively . (ci . - )/ . ( . - ) for a e/e' .the best thresholds of e/e' in low lvef was . with a sensitivity of (ci - ) % and a specificity of (ci - ) %. for low and normal lvef auc roc was respectively . (ci . - . )/ . (ci . - . ) for the pvc. volume approach: for low and normal lvef, the auc-roc for fluid responsiveness was respectively . (ci - ) and . ( . - ). the best thresholds in normal lvef was an edvi below ml/m wit a specificity of (ci - ) and a sensitivity of (ci - ) %. discussion our study shows a variation of the diagnostic value of e/e' and edvi according to the left ventricular systolic function. therefore, the systolic function should be taken into account to analysed the e/e' and edvi value. few preload dependency markers are validated in children and none for children in spontaneous ventilation ( ) . our study suffers from a lack of power that calls into question the validity of our results. another limitation is that both approaches with volume and pressure are not very discriminant as it is known for static value in adults. our study illustrates that, on a pressure-volume curve, when the cardiac inotropism is reduced, the filling of the left ventricle is moved to the up and right of the curvilinear diastolic function curve. therefore, pressure variations are larger than volume variations. these values should be monitored on a larger scale to define their exact diagnostic value. conclusion static pvc value is a low preload-dependency surrogate. when lvef is low a pressure evaluation based approach seems more accurate. when lvef is normal a volume evaluation based approach seems informative as predicted by the slope of the end diastolic pressure volume curve. those both static approaches remain of poor diagnosis accuracy. introduction acute viral bronchiolitis is a primary cause of respiratory distress in paediatric intensive care unit (icu). prone position (pp) is commonly used in neonates to improve respiratory mechanics and has been found beneficial to adult patients with acute respiratory distress syndrome. we aimed to evaluate the effect of pp on work of breathing as compared to supine position (sp) in children with severe bronchiolitis requiring non-invasive ventilation. the protocol was approved by our irb ( -a - ). fourteen infants ( boys) with median age days [firstthird quartiles - ] with severe bronchiolitis requiring cpap were included after written informed consent. children were investigated in pp and sp each applied for h in a random order with a washout period of min between them. level of cpap was set at cmh o in both conditions. oesophageal pressure probe was inserted orally (cto- pressure transducer, gaeltec, scotland) to measure oesophageal pressure. flow and airway pressure (pmo in fig. ) were simultanuously recorded using a neurovent data acquisition system (neurovent inc, toronto, canada). one hundred breaths were analyzed in each condition, in which work of breathing was estimated from oesophageal pressure-time product (ptpes) and oesophageal swings (fig. ). data were expressed as median (first-third quartiles) and compared by using the wilcoxon two-sample paired sign test. a p-value below . was considered significant. . the edtb contains data from ventilated patients (invasively and non-invasively) and details concerning ionotropic and sedative treatment during picu courses. discussion as far as we know, this edtb is currently the only one as exhaustive available in picu worldwide. after almost years of multidisciplinary collaboration, we are able to collect many useful physiological, therapeutic and medical data in an ongoing edtb. although many concerns remain concerning data validation, organisation and exploitation, this edtb already contribute to the development of clinical decision support systems and virtual patient validation and we create international collaborations to further develop these tools. three research protocols using the database are ongoing including: validation of a neuromonitoring clinical decision support system, validation of a cardio-respiratory simulator, developement and validation of the automatic diagnosis of pediatric acute respiratory distress syndrome and development of spo forecast using artificial neuronal network. conclusion thanks to informatics and electronic devices improvement, data gathering in intensive care units has empowered. we hope that our work in picu will encourage other teams on the way of data gathering, in order to build an international picu edtb in a close future. none. introduction severe trauma is rare in the pediatric setting ( % of all trauma in france). however, its morbidity and mortality remain high, in relation to brain injury. pediatric traumatic brain injury (tbi) prehospital care is challenging for non-pediatric retrieval teams. though, we disseminated pediatric tbi pre-hospital care regional guidelines and thereafter intended to assess severe pediatric trauma pre-hospital care and secondary cerebral insults control. we conducted a retrospective study in a single pediatric trauma center. children admitted in emergency room with severe trauma and moderate to severe tbi (glasgow coma scale ≤ ) from june to march were included. pre-hospital and hospital data regarding primary care, equipment, medications and secondary cerebral insults control (i.e. blood pressure, oxygenation, co level, temperature, glycemia) were collected from medical files. two pediatric transport team experts assessed the quality of pre-hospital care, based on two major endpoints. results twenty-nine files were analyzed. median iss was . all the children had been referred directly from the trauma scene to the pediatric trauma center. they were all intubated in the prehospital setting, ( . %) presented with spo < % before or at emergency room admission, and ( . %) presented with a pco > mmhg at admission. at least one peripheral catheter was inserted in all the children. mean total fluid bolus was . ml/kg (± ). nor-epinephrine was administered in ( %) children. mean blood pressure was below age threshold in ( %) children during transport or at admission. an intracranial hypertension treatment (apart from sedation) was delivered in ( %) children before admission. body temperature was monitored in patients and were hypothermic at emergency room admission. experts concluded on sub-optimal care in children: major endpoint was "respiratory care", "hemodynamic care" and "neurologic care" in , and patients respectively. discussion on this small series, we showed pre-hospital sub-optimal care regarding secondary cerebral insults control, especially regarding co level, blood pressure and body temperature. our results will help to design new care improvement strategies (e.g. sedation, fluid bolus and ventilation optimization, early use of vasoactive drugs, systematic body temperature monitoring…). conclusion data on pre-hospital secondary cerebral insults care are rare in the pediatric setting. based on our results, we aim to improve quality of care of children presenting with traumatic brain injury, and to reduce its morbidity and mortality. introduction unsuccessful extubation from mechanical ventilation increases mortality and morbidity. to reduce the extubation failures in our intensive care unit we used a mechanical ventilator weaning protocol, based on published data. during the first part of the study, risk factors and incidence of extubation failure were first described. afterwards in the second part, our mechanical ventilator weaning protocol was tested to determined its efficiency regarding the extubation failure. patients and methods a monocentric and observational study, was first conducted. we included children aged from birth to old, during a period of months and collected for each patient their medical history, intubation and extubation parameters, and existing events of extubation failure or extubation complication. the second part of the study was prospective, we include patients extubated by applying our mechanical ventilator weaning protocol. results average duration of mechanical ventilation was . h in the first part of the study. using a univariate analysis, duration of mechanical ventilation was a risk factor of extubation failure with an average duration of . discussion our study confirms published data about extubation failure risk factor like duration of intubation, chronic respiratory affection, history of previous intubation, and the administration of benzodiazepine. it is the first pediatric study that shows a reduction of extubation failure by using a specific mechanical ventilator weaning protocol. the mean bias of our its retrospective and prospective character. conclusion our study shows the interest of a mechanical ventilator weaning protocol to reduce the incidence of extubation failure. we currently continue the apply our protocol to include more patients in order to confirm our results. stroke of the child is formidable though it is ten times rarer than in adults, but this scarcity can have adverse consequences on the speed and quality of the management and the consequences on later psychomotor development. our goal is to describe the clinical and therapeutic aspects of these pediatric stroke while bringing our experience. patients and methods retrospective study of cases of children hospitalized in general intensive care unit to the pediatric hospital canastel oran for stroke during the period from january to january . the clinical, etiological, para clinical, and scalable were studied and transcribed on a standard electronic form.all patients had a brain ct. magnetic resonance imaging(mri) was possible in patients for lack of availability of the technical facilities during the study. results ten cases were selected. the mean age was months ( month to years), % are male, patients had a history of chd like tetralogy of fallot and complicated bronchiolitis myocarditis, one patient had a history of petechial purpura, other was a factor deficiency, headache history was noted in patients, and patients with no particular antecedent was found. all patients arrived comatose / score on the scale of glasgow, isochores reactive pupils with a motor deficit of hémicorps, patients have degraded their neurological score with onset of clinical signs of hypertension intra cranial namely anisocoria and hypertension requiring osmotherapy, sedation and mechanical ventilation with an average duration of - day. o child arrived brain dead, patients had generalized tonic-clonic seizures which yielded after taking a benzodiazepine (diazepam) and phenobarbital (like gardenal). cerebral ct was performed in all cases and could we revealed the nature of the stroke hemorrhagic in cases and ischemic stroke in cases. two patients have benefited from an mri that found a thrombosis of the artery internal carotid right sylvian. besides symptomatic treatment, treatment was initiated based on the type of stroke, patients received low molecular weight heparin (lmwh) at . ml/kg in addition to symptomatic treatment, patients received vitamin k. four patients died in an array of autonomic disorders and evolved favorably and six patients were transferred to a pediatric unit. the average length of stay in icu was . days ( - days). discussion the mortality rate is important since no specialized center for children, and difficulty especially in the diagnostic imaging field while suspected stroke should be confirmed by imaging and the diagnostic delay. which is due to a poor assessment of the initial situation in half of the cases by the parents, the other half by the swiss magazine consulté.une doctor showed that in a study in % of children with stroke, this diagnosis was not primarily discussed and that in % of cases the cause of the stroke was poorly evaluated [ ] . heart disease certainly represent the second most important risk factor. a collaboration of a team must be multidisciplinary, death has affected mostly older children whose age is between and years, who have a hemorrhagic stroke against by infants who have an ischemic stroke have evolved and oriented they exceed the acute phase to pediatric services for further investigation and monitoring. conclusion the child may also be having a stroke, which usually reaches the elderly. this justifies a good knowledge of this disease, and multiply the initial management efforts to reduce mortality and improve prognosis. anwar armel , benqqa anas , samira kalouch , khalid yaqini , aziz chlilek introduction nosocomial infections are a main problem for public health for their cost as well as for the morbidity and mortality they generate. they are particularly common in intensive care units due to patient's lower defenses and of invasive procedures proliferation. work's purpose: • determine the epidemiology of bacterial noso-comiales infections (ibn) in the medico-surgical pediatric intensive care department of children's university hospital of casablanca. • to identify factors associated with these infections. we led a retrospective study of hospitalized patients, spending more than h in medical-surgical pediatric intensive care department, at the university hospital ibn rochd of casablanca, over a period of months from january to december . results during the studied period, patients were admitted at intensive care with a stay of more than h. thirty episodes of inb were recorded. the incidence rate was . % and the incidence density was . % per hospitalization's days. the admission average age was . ± -month starting from month to years with a male predominance ( %). most of admissions ( %) was related to medical background, . % received from other hospital department. furthermore, % of the patients received prior antibiotics, usually prescribed before icu admission. invasive procedures (intubation, central catheterization) were used in . % of patients, vvp only in . %, tracheotomy in . and . % had received surgery. gram-negative bacilli (bgn) were isolated for a lot of patients, dominated by acinetobacter baumannii. these bacteria were isolated throughout the study year. risk factors analysis underlined that the presence of invasive procedures enhances in risk, that is central venous catheter and the need for mechanical ventilation. conclusion nosocomial bacterial infections are dominated by pneumonia and central catheter infections, and are mainly due to bgn. the factors associated with these infections were identified. the guillain-barré syndrome (gbs) is the most common cause of acute flaccid paralysis in children since the acute anterior poliomyelitis eradication. few studies have been held on the topic and knowledge of gbs in children, although it is recognized that the etiologic mechanisms, and clinicobiological background, are the same as in adults, prognosis remains different. our work's aim is to study this disease's mortality factors of children hospitalized in pediatric intensive care. patients and methods it is a retrospective, descriptive, mono centric study to review patients with gbs between january and december and hospitalized at pediatric intensive care department of abderrahimharouchi hospital of casablanca. the used software is spss . to compare the bivariate variables, we used the khi test, and to compare quantitative variables, the anova to factor test was used. the level of significance was fixed at % with % confidence interval. the disease was predominant in male with a sex ratio of . men/women. after a prodromal event, usually infectious ( . %) and a free interval of days on average to start motor disorders. these are of two types: either a hypo or areflectic flaccid paralysis of the lower limbs ( . %) of ascending evolution in . % of the cases. either flaccid tetraplegia or hypo areflectic, ( . %). ventilation was required in . % of the cases, and specific treatments based on immunoglobulins were administered in . % of the cases. death's rate is still high ( . %) and mainly due to hospitalization complications. in our study respiratory disease was noted in . % of the cases, also other signs of serious illness such as swallowing disorders ( . %) and autonomic disorders ( . %) also noted what led to management in intensive care for all our patients. these patients study allowed to identify some mortality prognosis factors of the disease in intensive care units (such as male gender, ig administration duration, the occurrence of autonomic disorders like blood pressure instability), the most discriminating remains the occurrence of nosocomial infections. conclusion it must be underlined, that in view of our strict inclusion criteria, focusing only on patients admitted at intensive care and of the relatively small sample size ( cases), our results must be qualified and must be enhanced by additional and more varied studies to better understand this disease in children. introduction early surgical treatment is recommended for refractory intracranial hypertension (htic) in children to improve vital and functional prognoses, whether traumatic or vascular cause. the main objective of this study was to compare the mortality and morbidity of children with severe intracranial hypertension after severe head trauma (tc) or due to vascular cause after decompressive craniectomy (dc) or medical therapy alone. the secondary objective was to identify the initial severity factors associated with higher mortality. patients and methods a retrospective study was performed with data collected from patients aged under years-old admitted to our pediatric intensive care unit for severe intracranial hypertension of traumatic or vascular cause, between january and january . they were divided into groups: patients who received medical therapy alone and those treated with decompressive craniectomy after optimal medical management. results a total of children were included. among them, were treated with dc ( htic of vascular cause and htic of traumatic cause), and were supported by medical means only ( htic of vascular cause and htic of traumatic cause). in the population "traumatic intracranial hypertension", we note that children in the "dc" subgroup are more often in mydriasis upon arrival (p = . ) than in the subgroup treated medically. in this same population, children in the "dc" subgroup received higher doses of mida-zolam (p = . ), of mannitol (p = . ) and hypertonic saline (p = . ) than in the other subgroup. in the population "vascular intracranial hypertension" the two subgroups were comparable. in the case of traumatic intracranial hypertension, mortality rate in the "dc" subgroup was . % against . % for children treated medically (p = . ); "dc" children had more metabolic complications such as hypernatremia than "not dc" children, p = . . mortality rate in the «vascular intracranial hypertension» group was % for children treated with decompressive craniectomy, and . % for children treated medically alone (p = . ). patients treated surgically in the «vascular intracranial hypertension» group had longer overall stays (p = . ) and longer icu stays (p = . ). popc score (pediatric overall performance category) upon discharge for children with intracranial hypertension of traumatic cause treated with decompressive craniectomy was . ± . against . ± . among children treated medically, p = . . in "dc" children with intracranial hypertension of vascular cause, popc upon hospital discharge was . ± . against . ± . among non-operated children, p = . . the schooling rate was higher among children treated medically for intracranial hypertension of traumatic cause, p = . . the severity factors related with higher mortality identified in the population "traumatic intracranial hypertension" were mydriasis upon admission, a pim score higher and a lower temperature (< . °); the latter being the only factor identified for htic of vascular cause. in the case of traumatic intracranial hypertension, icp monitoring in survivors was . % against . % in children died, with no significant difference. in the population "vascular intracranial hypertension", all the patients who died had not been monitoring pic. discussion the severity factors related with higher mortality identified in the population "traumatic intracranial hypertension" were mydriasis upon admission, a pim score higher and a lower temperature (< . °); the latter being the only factor identified for htic of vascular cause. other studies have related other severity factors as initial glasgow scale, tardive decompressive craniectomy. conclusion decompressive craniectomy doesn't seem to improve the mortality rate or the outcome in patients with hypertension of traumatic cause in our study but the dc traumatic subgroup was more serious than the subgroup treated medically. in children with refractory intracranial hypertension of vascular cause dc significantly improves survival and outcome. further studies are needed to clarify the role of decompressive craniectomy and its timing in the therapeutic management of refractory intracranial hypertension. introduction shortage of heart grafts is a major problem, leading to a significant mortality rate in the national waiting list, essentially for young children with low weight. the potential paediatric brain-dead donors often have myocardial dysfunction (md), which seems to be reversible. the aim of this study is to assess prevalence, causes and consequences of md when the potential paediatric donors are taken over, up to multi-organ retrieval, and the evolution after cardiac transplantation. materials and methods this observational, monocentric, retrospective study included all brain-dead children aged - years old, who had their myocardial function assessed through a cardiac ultrasound performed by a cardiologist and identified from to . all adult patients and those who didn't undergo a cardiac ultrasound were excluded. md was defined as an lvef ≤ % with or without abnormal segmented cinetic parameters. the main evaluation criteria was the prevalence of md in potential identified donors. the secondary evaluation criteria were the causes and consequences of md on heart retrieval and the origin of this md. results out of included patients, had md. prevalence of md was of %. there was no significant difference between groups regarding aetiology of brain death nor administration of catecholamines. having a cardiopulmonary arrest during intensive care unit stay was associated with a significant risk of presenting a md (p = . ). having a md had no consequences on organ retrieval in general (p = . ), but was significantly associated with a decrease in heart retrieval opportunities (p = . ). the cause of heart grafts refusal was a poor ventricular function in % of cases ( cases out of ). the cause for non-retrieval was parental refusal in one-third of cases. evolution of the cardiac grafts was favorable in cases on , one transplanted patient died (from a non-cardiac cause) and patient was lost to follow up. conclusion md in paediatric brain-dead patients has direct consequences on heart retrieval and transplantation, and otherwise, organ shortage is a major ongoing problem. a better transplant management regarding hemodynamics (with the use of a protocol) could increase the number of heart transplants, especially in small children, and reduce mortality rate in national waiting list. the prone positioning (pp) is a strategy widely used in the treatment of severe forms of acute respiratory distress syndrome (ards) in adults. its early use significantly reduces mortality ( ). however, the studies do not strongly demonstrate its prognostic impact in pediatric ards. the aim of this study was to describe the prone positioning practices in the french-speaking pediatric intensive care units (picu). patients and methods this survey was conducted by email questionnaire to pediatric intensivists belonging to the french society of intensive care medicine and the french-speaking group of pediatric intensive care and emergency medicine. it was conducted from february to may . the survey was addressed to doctors, nurses, physiotherapists practicing in picu. it included questions about indications, contraindications, techniques and medical devices used, and complications. results one hundred and three persons answered ( doctors and nurses) which work in french hospitals and canadian hospital. sixty-eight percent of interviewed persons have more than years experience and % of them treat each year more than children ards. only % of the picu have a pp medical protocol. fifty percent of interviewed persons frequently use pp for the medical care of ards and % systematically use it. thirty-six percent begin pp at the early phase of ards during conventional ventilation, while % before the introduction of unconventional ventilatory strategies (ohf); only % use it after the respiratory failure unless unconventional ventilatory strategies. seventy-three percent report that pp is used with prolonged periods (> h/day), % with short periods (< h/day) and % with very long periods (> h/day). regarding the weaning criteria, most of interviewed persons seem to use multiple and combinated criteria: % use hypoxemia severity parameters (pao /fio , pao , sao ), % use the oxygen level (fio ) and % use the mechanical ventilation parameters (peep, p max, p plate). finally, despite a low level of scientific evidence in children, % of the persons gave a strong recommendation for pp as standard care in severe pediatric ards. see fig. . the survey confirmed the widely use of pp in pediatric ards. however, no specific protocol is avalaible in most of the picu. the timing of the pp beginning can be different according to children, early and prior to use of the conventional ventilation strategy in most cases. the duration of pp seems more consensual. most of the centers use extended periods longer than h/day. these results are close to guérin et al. advocating a duration > h/day. finally, the weaning is a great issue and depends on multiple criteria. in guerin et al. ( ) pp was interrupted if one of the following criteria were present: pao / fio ≥ mmhg, with peep of ≤ cm of water and a fio of ≤ . ; decreased pao /fio than %, compared to compared to the supine position, or the occurrence of complications. no study has validated pp weaning criteria during pediatric ards. conclusion the prone positioning is a strategy commonly used in pediatric intensive care units for the severe pediatric ards. the criterias of implementation and timing are variable, as well as the weaning criterias. more pediatric multicenter randomized studies will be necessary to confirm the benefits of pp in pediatric ards and to define clear weaning criteria. introduction allogeneic hematopoietic stem cell transplantation (hsct) recipients have profound defects in every immunity compartments that can lead to severe opportunistic infections (oi). % of hsct patients require admission to the icu because of diverse infectious or non-infectious complications with dismal outcomes. oi specific course in this population has not been described previously and the management of these infections may be a concern. the aim of this study was to investigate risk factors, management and outcomes of io in hsct recipients admitted to the icu. patients and methods this was a retrospective ( - ) single center study of patients admitted to icu after an allogeneic hsct. patients provided written informed consent according to helsinki declaration. data regarding the transplant, infections and life sustaining therapy use were analyzed. oi were considered if present at the time or during icu admission. results hundred and ninety-four patients (pt) were included. median age was [ ; ] years, . % were males. reason for transplantation was acute leukemia in ( %) pt and the hematological condition was still in complete remission at icu admission in % of patients. ( %) and ( %) had received a myeloablative conditioning regimen and anti-thymoglobulin serum respectively. % had acute graft versus host disease over grade at icu admission. oi was documented in patients ( %). an invasive fungal infection (ifi) was found in pt owing to mucormucosis, trichosporon septicemia and invasive aspergillosis ( possible, probable and proven according to eortc criteria). serum galactomannane antigen was positive in ( %). median time from transplantation and icu admission to ifi diagnosis was respectively [ ; ] and − [− ; ] days. lung was involved in % and patients with aspergillosis were admitted to the icu for acute respiratory failure in % (vs. % for others p = . ). they did not required invasive ventilation more frequently ( vs. % p = . ). and % required vasopressors and renal replacement therapy with no difference as compared to others. median icu length was [ ; ] days. demographic, stem cell source, and donor type were not associated with ifi occurrence in this population. however / had received a total body irradiation ( vs. % p = . ). ifi occurrence was not associated with icu or day mortality ( vs. % p = . and vs. % p = . respectively). a viral infection was found in pt owing to cmv, adenovirus, hsv and vrs infections. analyses were focused on cmv reactivation. median time from transplantation and icu admission to cmv reactivation was respectively [ ; ] and − [− ; − ] days. reactivation was mainly positive blood pcr but pt had cmv colitis. a preemptive treatment was started on the same day in median and lasts [ ; ] days. patients with cmv reactivation had more frequently multiple organ failure ( vs. % p = . ) and higher icu admission sofa score ( [ ; ] vs. [ ] [ ] [ ] [ ] [ ] [ ] p = . ). they trend to have higher admission creatinine serum level ( [ ; ] vs. [ ; ] umol/l, p = . ) and more frequently required emergency renal replacement therapy ( vs. % p = . ) mechanical ventilation ( vs. % p = . ) and vasopressors ( vs. % p = . ). median icu length was [ ; ] days and comparable to others. demographic, stem cell source, conditioning regimen and donor type were not associated with cmv occurrence. cmv reactivation was not significantly associated with icu or day mortality ( vs. % p = . and vs. % p = . respectively). conclusion oi was found in % of allogeneic hsct recipients admitted to the icu. ifi were mainly responsible for respiratory distress and cmv associated to multiple organ failure. non-invasive diagnostic tests were positives in a majority of these patients. in this cohort, io treatment was started quickly after the diagnostic and we did not find an association with mortality. intensivists should always consider oi in their diagnostic panel in this specific population. introduction over the last two decades, targeted therapies in patients with solid tumors have both increased their length of survival and significantly altered their immune functions. however, data on opportunistic infections in this setting remain scarce. in this systematic review, we sought to identify published cases of opportunistic infections in patients with solid tumors, with a special interest on clinical findings, trends over time and outcomes. materials and methods we performed a search of medical subject headings (mesh) on pubmed using the words pneumonia pneumocystis (pcp), invasive aspergillosis (ia), histoplasma, mucor, geotrichum, cryptococcus, coccidioidomycosis combined with the mesh term neoplasms (breast, lung, ovarian, urologic gastrointestinal, digestive system, abdominal, brain, carcinoid tumor, sarcoma, testicular, seminoma). we identify published cases of opportunistic infections in non hiv patients with solid tumors between / / and / / included. results regarding pneumocystis jirovecii pneumonia, cases could be identified. there were men and women, aged of . ( - ) years. underlying tumors were chiefly brain neoplasms (n = , %), lung neoplasms (n = , %) and breast neoplasms (n = , %). at the time of pneumocystis pneumonia onset, patients ( %) had a history of chemotherapy, ( %) had received long term or high dose steroids, and ( %) had an history of biotherapy targeting the malignancy. of note, patients ( %) had received only chemotherapy, ( %) had received steroids alone, ( %) everolimus therapy alone and ( %) received none of these treatments. regarding invasive aspergillosis cases could be identified. mean age was . ( - ) and ( %) were men. solid tumors associated with invasive aspergillosis were primarily lung neoplasms (n = , %) and brain neoplasms (n = , %). at aspergillosis onset, ( %) patients had a history of chemotherapy, ( %) were receiving long term or high dose steroids and ( %) had received targeted therapy. fourteen ( %) patients had received only chemotherapy, ( %) only steroids, and ( . %) had received targeted therapy alone. for both infection, there was a trend for a higher number of reported cases throughout the studied period. conclusion this systematic review provides objective data showing that an increased proportion of patients with solid tumors present with opportunistic infections. we are convinced that it is a clinically relevant but still neglected problem. selected oncologic population may be becoming eligible for antimicrobial prophylaxis against pneumocystis or aspergillus. care unit of strasbourg in france. patients were included only if they are non-immunocompromised according to the european organisation for research and treatment of cancer (eortc). invasive aspergillosis was defined as an association of microbiological evidence, a radiological imaging and a clinical context. results eighteen patients ( males) were identified during the study period. the median of igs ii was . (interquartile range (irq), . - . ). ninety-four percent was under mechanical ventilation. fourteen ( %) patients were suffering from liver failure. among liver failure, twelve ( %) were beforehand suffering from cirrhosis. the median meld score was (interquartile range (irq), - ). sixty-four percent of aspergillosis were due to aspergillosis fumigatus. hundred percent were pulmonary aspergillosis. fifty-six percent of aspergillosis were associated with bacterial pneumonia. the mortality rate at the date of the latest news (an average of years) was seventytwo percent. discussion invasive aspergillosis is not exceptional in the non-immunocompromised patient especially in patient developing liver failure. an active research of colonization/infection with aspergillus in these patients remain to be discussed. conclusion invasive aspergillosis in icu has a poor prognosis. the liver failure seems to be the most important risk factor in non-immunocompromised patients according eorct criteria. introduction chest wall elastance (ecw) has been found to increase in prone (pp) as compared to supine position (sp) in ards patients [ ] . this makes respiratory system elastance (ers) not reflecting lung elastance (el). little is known about the changes of ecw, el and lung resistance (rl) when moving the patient from the sp to the pp via the lateral position (lp). the goal of present study was to measure ecw, el and rl in ards patients in sp, lp and pp during the proning procedure. patients and methods it was a prospective, single-center, controlled study. ards patients intubated, sedated and paralyzed with pao /fio ratio < mmhg, peep ≥ cmh and an indication of pp were included. mechanical ventilation was delivered in volume controlled mode with constant flow inflation and end-inspiratory pause . s included into the inspiratory time. ventilator settings were unaltered during the procedure. an esophageal balloon catheter (nutrivent device) was used for esophageal pressure (pes) measurement. pressure at the airway opening (pao) and airflow were measured by fleish pneumotachograph proximal to endotracheal tube and upstream heat and moisture exchanger. pao, pes and airflow were continuously measured during min in sp, then during min in lp and min in pp. the side for the lateralization was that selected by routine practice (in the opposite side from central venous line). ers and resistance of the respiratory system (rrs) were obtained by fitting flow and pao signals breath by breath to the first order equation. ecw and resistance of the chest wall (rcw) were similarly obtained by fitting flow and pes signals breath by breath to the first order equation pertaining to the chest wall. el and lung resistance (rl) were obtained by subtracting ers and rrs from ecw and rcw, respectively. our ethical committee approved the protocol. data are shown as median (first and third quartiles). comparisons between positions were made by using paired-t-test. results twenty-nine patients, males, of ( - ) years, saps ( - ) and sofa score ( - ) were included ( - ) days after ards criteria were met. the ards severity was moderate in cases ( %) and severe in ( %). tidal volume averaged . ( . - ) ml/kg predicted body weight, peep ( - ) cmh o, fio ( - ) %, pao /fio ( - ) mmhg. the cause of ards was pulmonary in cases ( %), extra pulmonary in ( %) and undetermined in ( %). lateral positioning was on the right side in ( . %) and on the left side in patients ( . %). the results are shown in the table . conclusion during prone positioning in ards patients, as compared to sp we observed a higher rl in lp and an increased ecw in pp. introduction neuromuscular blocking agents (nmba) could exert beneficial effects in acute respiratory distress syndrome (ards) through properties on respiratory mechanics and particularly in modifying transpulmonary pressures (pl). patients and methods prospective randomized control study in moderate to severe ards patients within the first h of the onset of ards. all patients were monitored by an esophageal catheter and followed during h. moderate ards patients were randomized in two groups according to the systematic administration of a h continuous infusion of cisatracurium besylate or not (control group). the severe ards patients group received a h continuous infusion of cisatracurium besylate. the evolution during the h of the study of the oxygenation and the respiratory mechanics including inspiratory and expiratory transpulmonary pressures and driving pressure were assessed and compared. delta transpulmonary pressure (∆pl) was defined as inspiratory pl minus expiratory pl. results thirty patients were included, in the moderate ards group and in the severe ards group. nmba infusion was associated with an improvement in oxygenation both the moderate and the severe ards patients group accompanied by a decrease in both the plateau pressure and the total positive end expiratory pressure. the mean inspiratory and expiratory pl were higher in the moderate ards patients group receiving nmba as compared with the control group (fig. ) . in contrast, there was no modification of both the driving pressure and the ∆pl related to nmba administration. conclusion nmba could exert beneficial effects in moderate ards patients through higher observed inspiratory and expiratory transpulmonary pressures. none. introduction prone position (pp) is a major treatment in management of acute respiratory distress syndrome (ards). the use of pp in patients with severe ards associated with brain injury is at high risk of intracranial hypertension. the aim of this study is to analyze the effect of pp on intracranial pressure (icp) and cerebral perfusion pressure (cpp) in patients with ards and acute neurological condition requiring monitoring of icp. patients and methods it is a retrospective descriptive study including sixteen patients with acute brain injury (subarachnoid hemorrhage, severe head trauma, and hemorrhagic stroke) and continuous monitoring of icp who developed a severe ards during icu stay from january to december and for which pp was performed. pp sessions were analyzed. hemodynamic and respiratory parameters, blood oxygenation, pic and ppc were studied in supine, before pp and after pp. the study was approved by fics ethic comity. results a significant increase in pao /fio ratio was observed in pp, from ± to ± (p < . ). in pp, the icp was increased ± . - ± . mmhg (p < . ) while the cpp was stable ± versus ± mmhg (ns). median duration of pp session was h ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . increasing of icp during pp required medical treatment in sessions ( %). pp session was interrupted in sessions ( %). in subgroup of patients who respond to pp in terms of oxygenation, the increase of icp was lower than in non-responders ( vs %) (p < . ). cpp was not modified whatever the nature of the response to pp ( ± - ± in non-responders and from ± to ± in responders (ns)) (fig. ). discussion our study shows an improvement of oxygenation during pp in severe ards patient with acute brain injury. we observe a constant increment of pic during pp sessions. the increment of icp is less in responders to pp. significant increased icp requiring an enhancement in the medical treatment was observed in % of the cases, and lead in most cases to a discontinuation of the session. our data underlined the absolute necessity to monitor icp during pp session in patients with acute brain injury and ards, even if icp is controlled previously in supine. only prospective ( , ) and one retrospective studies evaluate the effects of pp on icp in patients with acute brain injury and acute respiratory failure (arf). they results are similar to ours. in all these studies, the severity of arf was often not well specified. roth and al. ( ) had included only % of ards in a population of patient with icp not controlled. in others studies, monitoring of icp during pp was not systematic. despite the retrospective nature of the study and the small number of patients, it is the only work studying the effects of pp on intracranial pressure in patients with acute brain injury at risk for intracranial hypertension and severe ards according to the berlin's definition. conclusion our work suggest that pp is a quite secure technique for use for the treatment of severe ards even patients at risk of intracranial hypertension with a benefit in terms of oxygenation without major increase of icp particularly in pp responders. introduction influenza-associated acute respiratory distress syndrome (ards) requiring extracorporeal membrane oxygenation (ecmo) support is known to have a good prognosis ( ). however, the incidence and impact of co-infection in this setting remain unknown. we conducted a retrospective, observational analysis of data prospectively collected from all patients admitted to our medical icu who received ecmo support for influenza-associated ards between and . co-infection was defined as isolation of a pathogen in the lower respiratory tract at a significant level or in the blood during the h following hospital admission. when no pathogen was identified in a patient receiving antibiotics prior to bacteriological sampling, an independent adjudication committee reviewed all charts to assess if the patient had a "high probability" or "low probability" for bacterial co-infection, based on clinical, radiological and biological results available. results are presented as median [iqr] . results among the patients hospitalized for an influenzaassociated infection in our icu, had an ards requiring support by either veno-venous-(vv, n = ), venoarterial (va, n = ) or venoarterio-venous-(vav; n = ) ecmo. - . ), pre-ecmo sofa score > (or . ; % ci . - . ) as independent predictors of hospital mortality, but not co-infection (or . , % ci . - . ). in a second analysis, patients with proven co-infection and high probability of co-infection were grouped and compared to patients with no co-infection and low probability of co-infection; and results were similar. as compared to others co-infected patients, those co-infected with a pvl-positive s. aureus had same characteristics and similar mortality rate, but all received a treatment active against pvl production. conclusion co-infection is frequent in patients with influenzaassociated ards supported by ecmo, occurring in roughly % of the cases. mortality of patients with co-infection is higher than those without, but seems mainly due to the severity of the disease. s. aureus was the most frequently identified pathogen, with a high prevalence of pvl-positive s. aureus, infection with a pvl-positive strain was not associated with a poorer outcome as compared to other co-infections. whether a treatment active against pvl production should be given in those patients remains to be determined. none. the pancreaticoduodenectomy (pd) is major surgery in visceral surgery. this technique performed for the first time in by whipple has seen much progress and development over the years that have enabled a significant reduction in mortality, while the morbidity remains high. the aim of this study was to analyze postoperative morbidity pancreaticoduodenectomies. we retrospectively studied cases of cephalic duodenopancreatectomy at the department of surgical emergencies resuscitation (wing ) spanning years, between january and december . the average age of patients was . years with % of females and % of males, the frequence of pancreatic resections was years. the indications of cephalic duodenopancreatectomy were: tumors of pancreatic head ( %), ampulla vater ( %), duodenum tumors ( %). the restoration of continuity after cephalic duodenopancreatectomy was realized with a rate of % for pancreaticogastrostomy and % for pancreaticojejunostomy. the average hospital stay was , days, with extreme lengths of - days. the postoperative course was marked by the occurrence of deaths ( %), the morbidity rate was , % after pj and % after pg; the most frequent complications were the pancreatic fistula ( %), the postoperative peritonitis ( %), the digestive bleeding ( %), the gastroparesis ( %). conclusion advances in the overall care of patients by surgical teams, anesthesiologists and intensivists, the dpc mortality is currently low in experienced centers. the multidisciplinary, involving surgeons, radiologists and especially intensive care, to manage more effectively the complications of this surgery remains burdened with high morbidity. introduction severe acute pancreatitis (sap) is a common but potentially lethal pathology due to the multiplicity and severity of complications that can occur at all stages of evolution. in the last decade, mini-invasive interventional treatments of infected pancreatic necrosis (ipn) have been developed. the aim of the present study was to assess the management and outcomes of sap patients, as well as to identify the role of ipn. this was a retrospective study of prospectively collected data from all consecutive patients admitted in intensive care unit (icu) in a single french center (hospital of nantes) from to . using logistic regression, we evaluated the association between ipn and patients characteristics at baseline and the outcomes. (fig. ) , highlighting the prognostic importance of respiratory failure and acute renal failure at the time of lt, as well as complex interactions between donor and recipient features. conclusion ventilator support and/or acute renal failure at the time of lt are major predictors of mortality but complex recipients/donors relationships may moderate these associations, as demonstrated by our cart analysis. none. subtotal gastrectomy ( / ). enlarged gastrectomy was performed in patients ( %). the mean operative time was . ± min. per-operative transfusion was required in patients ( . %). the average length of stay in icu was . ± days. postoperative mortality was . %. in our series, patients ( . %) had at least one postoperative complication: an anastomotic fistula diagnosed in patients ( . %), patients ( . %) had postoperative peritonitis and patients had ventilator associated pneumonia. reoperation was necessary for patients ( . %), it was performed after . days ( - days). in univariate analysis, risk factors for postoperative morbidity after gastrectomy was hypoalbuminemia (p = . ), anemia (p = . ), bmi (p = . ) and malnutrition (p = . ). age, sex, neoadjuvant chemotherapy, extended lymphadenectomy, splenectomy or pancreatosplenectomy, total gastrectomy and operative time were not significantly associated with higher postoperative morbidity. in multivariate analysis, malnutrition (p = . ) and bmi (p = . ) were significantly associated with the occurrence of postoperative complications. conclusion the results of our study are similar to those reported in medical literature. preoperative evaluation and nutritional rehabilitation are crucial to improve patient's outcome and reduce morbidity and mortality after gastrectomy for cancer. the mesenteric ischemia is a condition relatively rarely. it is marked by high mortality. mortality is primarily related to the land on which ischemia occurs and especially the time taken to diagnose. this delay is due to the low specificity of clinical signs and the absence of diagnostic laboratory test. the mesenteric ischemia remains a diagnostic and therapeutic challenge. patients and methods twenty cases of acute mesenteric ischemia have been collected at the surgical resuscitation (resuscitation ) at the hospital center ibn rochd of casablanca from january to december . results the mean age of our patients is year old. it is about a disease that the incidence increases these last years, particularly because of the waxing number of old patients and/or suffers from advanced cardiovascular diseases. the cardiovascular risk factor has been present in % of our patients. the abdominal pain has been present in all the patients. it is a sudden, intensive pain localized the most often at the level of the epigastria, becomes diffuse in few hours or even few days. other clinical signs have been described as the bilious vomiting that becomes fecaloid after few days. the digestive hemorrhages as the moelena and the hematemeses. a stop of the matter and the gazes was noticed in % of our patients. the absence of specificity of the clinical signs forced the realization of complementary examinations. the scanner becomes the reference imaging. it permits a differential diagnosis, the search of direct signs of vascular obstruction and the emphasis of intestinal pain. four etiologies are noticed: the arterial occlusion by emboli ( %), the arterial thrombosis ( %), the venous thrombosis ( %) and the "non occlusive" form ( %). the strategy of management of the acute mesenteric ischemia is multidisciplinary, based on the equips of radiology, vascular surgery and/ or visceral surgery and resuscitation. the treatment consists in measures of general resuscitation, the techniques of endoluminal vascular disobstruction and techniques of surgical revascularization. in spite of the improvements in the diagnosis and the therapeutic procedure of the ima, the disease still know a rate of mortality between and % according the studies. in our study, we noticed cases of death ( %), cases of good recovery ( %), cases are unknown evolution ( %). conclusion it is a vital emergency that the evolution still knows great mortality. it is very important to remind the acute mesenteric ischemia in the case of any acute abdominal symptom in order to anticipate about the natural evolution and to act in a reversible stage of the ischemia. none. introduction emergency departments staff are frequently exposed to many complex stressful situations and consequently burnout syndrome. our study aimed to describe epidemiological particularities and determine the risk factors of burnout syndrome in different categories of emergency. patients and methods we studied five academics and four regional hospitals. the level of burnout was assessed using the "maslach burn out inventory" score and the degree of depression with major depression inventory (mdi) test. results one hundred and forty-three correctly completed questionnaires were collected. the mean age of study population was ± years. sex-ratio was at . . fifty-one per cent of the care staff were married. physicians represented % and paramedical %. the general frequency of burnout syndrome was % (n = ). low level burnout was present in %, moderate level in % and high level in %. the depression frequency was %. a statistically significant correlation was found between burnout and depression firstly (p = . ) and between burnout and lack of equipment (p = . ). their relative risk was . [ . , ] and . [ . , . ] respectively). main risk factors associated with high level burnout are detailed in table . conclusion burnout syndrome frequency in our emergency departments is alarming. helping to resolve social and psychological problems and improving work conditions may help to decrease it. the healthcare activity is recognized as a major polluting activity. in france, it generates , tons of waste cremated each year, and represents % of the tertiary energy consumptions. in the united states, it generates tons of waste per day and % of total co emissions in were attributed to him. ultimately, such waste production is associated with adverse environmental and health effects. nevertheless, near half of the hospital waste would be recyclable, particularly in our intensive care units (icu) [ ] . furthermore, sustainable development solutions generate profits. the aim of this study is to make an overview of waste produced in a icu and offer solutions to conserve natural resources and reduce the carbon footprint bound to the healthcare activity. materials and methods experimental study, single-center, concerning a period of months in an icu-high surveillance unit compound of beds. we have identified all waste generated. our packaging were given to the recycling company in connection with the hospital. then we have studied the impact of the implementation of sustainable development solutions. results firstly, we have studied the non-recycled waste and the quantity produced over a period of month. approximately kg of waste is produced per patient per day with % of infectious waste and % of general waste. these results were linked with a bad distribution of garbage bags in the rooms ( l of infectious waste versus l of general waste). secondly, we have improved our way to sort and consume and we have created recycling dies without compromising patient safety. all these measures have not increased workload. changing bags in the rooms ( l of infectious waste and bags of l of general waste) allowed to reach the normal goals of sectors with a net benefit estimated at euros per year. the medical broken glass containing drugs was thrown into plastic containers of l for infectious waste to prevent the risk of cuts. by creating a specific die intended to the general waste, we could quantify the production of this glass to kg per week and to spare the use and the incineration of containers of l per year (global economy of euros). plastic packaging represented an important proportion of the cremated waste. we have created sectors of recycling including the polypropylene ( - kg per month), the polyethylene colorless and colored polyethylene. this plastic is sold to be recycled without additional cost for the hospital. the linerboards was cremated. we have created a recycling die ( kg per month). this sector was subsequently extended to the entire hospital structure, particularly the pharmacy that produces containers of l per month. they are now sold without additional cost. many unnecessary plastic waste is generated daily. we have removed using mild soap plastic bottles of ml by using the same mild soap in pump of ml (economy of euros). the use of l plastic bags for the transitional deposit of linen has been deleted (economy of euros). concerning the paper: % of the impressions were made in simplex. printers were parametrized on both sides by default allowing the economy of reams per year ( , sheets), several thousand liters of water and the reduction of co emissions. discussion recycling is only one component of the sustainable development in health. other avenues that could be considered to improve icu sustainability would include examining water use (for linen), electricity use (reducing non-essential use at night…). beyond these actions, we need to encourage our suppliers to turn to sustainable and recyclable packages to reduce the use of polluting and depletable fossil fuels such as oil. but also to develop with them circular economies where waste is returned to them to be reused. conclusion we must ask the question also resuscitate our tons of waste. our icu produce large quantities of waste (over tons per year per bed). however, a significant proportion, especially plastic, is recyclable with a significant environmental and financial benefit. waste management also requires an optimal and rational use of supplies because "the best waste is that which is not produced" and that excess is not a guarantee of quality. as already said st exupéry in : "we do not inherit the earth from our parents, we borrow it from our children. " so do not expect tomorrow to reduce major adverse ecological impact paradoxically generated by a great profession whose ultimate goal is to cure people. moreover, an external consultant is rarely applied and palliative cares are insufficiently developed after «non-readmission» decisions. for providing corrective measures, this study lead to propose a «nonreadmission» process by integrating the discussion for a real «patient's care project» at the end of the icu hospitalization. this process would lead to collect patient's opinion through advance directives, to ensure a collegial discussion including an external consultant and to allow reevaluation of global patient's clinical status and one or more organ failure(s). then, «non-readmission» decisions would be integrated in a therapeutic project which would promote the initiation of a palliative care program if necessary. the purpose of this process is well to respect patient's autonomy and dignity as required by french law and medical ethics. the proportion of elderly patients is steadily increasing. due to the growth of this part of the population who suffer from multiple pathologies, the need for hospitalization in intensive care increases. according to the simulations, the proportion of octogenarian patients in icu will increase reaching the third of icu patients. while chronological age is not a significant factor of poor prognosis in the icu ( ), many factors should be taken into account to evaluate the relevance of icu admission in the senior population and withholding such intensification should be consensually discussed between clinicians and obviously as often as possible with the patient himself ( ) . the aim of the study was to assess the role of stakeholders (ward physicians, intensivists, family doctor and patient himself ) in the decision of withholding icu admission for elderly patients in our internal medicine department. we made a prospective observational monocentric study, including all the elderly patients (defined as older than ) admitted in the internal medicine department from january to june . the only non-inclusion criterion was patient's refusal to participate to the survey. collected data involve physiological (cognitive, autonomy, nutritional status), morbidities (acute and chronic diseases) and social parameters (marital status, relatives). and evaluation of quality of life by the patient himself using an analog visual scale was also obtained. internal medicine physicians were asked to report any icu withholds decision for their patients. in absence of notification, every physician was questioned again the day of the concerned patient's discharge. results one hundred ninety-one patients were included between january and june . factors associated with a significant reduction of in hospital mortality were higher age (p = . ), higher lactate level (p = . ), chronic obstructive pulmonary disease (p = . ), diabetes mellitus (p = . ), immunodepression (p = . ) and respiratory failure (p = . ). conclusion in patients hospitalized for vs high body mass index, low left ventricular systolic function, high white blood cell count, low creatinine clearance, high lactate level and st-segment depression are the variables correlating significantly with high-sensitivity troponin-t concentrations. peak of hstnt was not significantly associated with in-hospital mortality in this setting. introduction mitochondria are evolutionary endosymbionts that are derived from ancestral aerobic bacteria and so might bear and release bacterial molecular motifs supporting the role of mitochondria in danger signal regulations. free circulating mitochondrial dna (mtdna) is elevated in a wild range of critical illness observed in intensive care units, and is associated with bad outcomes and mortality. the mtdna is a molecular pattern that belongs to mitochondrial damage associated molecular patterns (mtdamps), and can interact with pattern recognition receptors (prr) to induce self defense reaction. free mtdna activates inflammatory signaling pathways through toll-like endosomal receptor (tlr ) interactions. nevertheless, new evidence advocates a role of the receptor for advanced glycation end-products (rage) in mtdna signaling. experimental data suggest a role of mtdna-prr interaction in systemic inflammation and organ dysfunctions as septic acute kidney injury or pulmonary inflammation. impact of free circulating mtdna on endothelial cell is not known. the main purpose of this study was to test whether mtdamps and mtdna can induce endothelial dysfunction. we also evaluated the role of mtdna-rage axis in mtdamps induced endothelial dysfunction. mitochondria were isolated from livers of wild type c b mice. isolated mitochondria were sonicated on ice to obtain mtdamp preparations. semi quantitative evaluation of mtdamp content was tested by qpcr, with specific markers of mtdna (cytochrome b (cytb), nadph oxidase (nd )). intraperitoneal injection of mg of mtdamps was used as experimental model in wild type and rage ko mice, as previously described [ ] . the mtdamps were also administrated after ex vivo dnase preparation. endothelial function was assessed with a mulvany-halpern style myograph, h after mtdamp administrations on aorta (conductive vessel) and on d division of mesenteric artery (resistive vessel). endothelial-dependent relaxation was studied by cumulative expositions of the vessels to acetylcholine ( . - - . - m). endothelial-independent relaxation was studied by sodium nitroprussiate exposition. results the mtdamps preparation contains a high quantity of mtdna with a /cycle threshold (ct) ratio of . for cytb expression. intraperitoneal administrations of mtdamps induced a decrease of endothelial-dependent relaxation mainly on conductive vessel (p = . , n = per group) and to a lesser extent on resistive vessel (p = . , n = per group). rage-ko mice were protected from mtdamps-induced aorta dysfunction (p = . , n = per group). the ex vivo exposition of mtdamps to a dnase preparation decreased mtdna content in mtdamps solution with a /ct ratio of . for cytb expression. eventually, the pretreatment of mtdamps with a dnase preparation prevented the mtdamps-induced aorta dysfunction (p = . , n = ). discussion more than prognostic markers, mtdamps particularly mtdna seems implicated in endothelial dysfunction in critically ill patient. new evidence suggest rage interaction in endosomal tlr pro-inflammatory and pro-oxidant response to mtdna [ ] . also in sepsis, physiological clearance of circulating dna might be impaired, this results comfort the possibility of therapeutic regulation of free circulating mtdna to prevent septic organ dysfunction related to mtdamps accumulations. conclusion exogenous mtdamps can induce endothelial dysfunction in mice. the mtdna-rage axis is a key component of the signaling pathway involved in this dysfunction. the use of dynamic parameters to assess fluid responsiveness was supported by cyclic changes in stroke volume induced by mechanical ventilation. however, these parameters have several limits. venous to arterial carbon dioxide difference inversely related to cardiac index. consequently, fluid administration would be beneficial if carbon dioxide gap increases. objective to investigate whether carbon dioxide gap predicts fluid responsiveness in patients with acute circulatory failure. patients and methods we conducted a prospective study in the medical intensive care unit of hospital taher sfar at mahdia, between march and april . patients with circulatory failure and who required mechanical ventilation were included. we measured the variation of cardiac index between baseline and after volume expansion of ml of saline fluid. the picco was used to measure cardiac index. response to fluid challenge was defined as a % increase in cardiac index. before and after fluid administration, we recorded carbon dioxide difference and hemodynamic parameters. results among included patients, ( %) were responders. the causes of acute circulatory failure were septic shock (n = ), cardiogenic shock (n = ), and hypovolemia (n = ). carbone dioxide gap was significantly higher in responders group ( ± vs ± mmhg, p = . ). the area under the roc curve for carbon dioxide gap was . ( % ci . - . ). the best cutoff value was mmhg (sensibility = %, specificity = %, positive predictive value = % and negative predictive value = %). the area under the roc curve for delta carbon dioxide was . ( % ci . - . ). conclusion in this study, baseline carbon dioxide gap was not universal indicator to predict the fluid responsiveness in patient with circulatory failure. introduction supraventricular arrhythmia (sva) is commun in intensive care unit (icu). its incidence seems to be higher in patients with sepstic shock. sepsis-associated myocardial dysfunction promote the occurrence of sva by constituting an arrythmogenic substrate or under the effect of inotropic drugs. the aim of this study is to assess the incidence and prognostic impact of sva in patients with septic shock. patients and methods we retrospectively studied all patients with new onset sva suffering from septic shock in non cardiac surgical icu. myocardial dysfunction was evaluated by transthoracic echography (tte) after an adequate cardiac resuscitation using intravenous fluids expansion and adjunctive vasoactive agents. sva was detected by the electrocardiogram scope. during the study period clinical and biologic characteristics, hemodynamic tolerance (vasopressors doses, arterial pressure changes), current treatment (such as corticoid), duration of mechanical ventilation, duration of vasopressor requirement and hospital mortality were collected. results sixty patients were included in the study. the sva occurred in patients, with an incidence of %. the median time to onset was days. cardioversion was performed for patients with an effectiveness of %. clinical and biological characteristics were similar between the groups with and without sva: saps and sofa score at the beginning of septic shock, the existence of ards and cardiac biomarkers (nt-probnp, troponin). however, renal failure and the use of corticoid in septic shock were more frequent in the group with sva. the maximum doses of vasopressor agent were not significantly different between the groups with or without sva. myocardial dysfunction in sepsis defined by the left ventricle ejection fraction (lvef) less than % (or the need for inotropic drug for lvef > %) was not associated with the occurrence of sva (+sva group: n = ; −sva group: n = ; p: . ). sva was poorly-tolerated, observed by a significant decrease in mean arterial pressure and a significant increase in norepinephrine doses within h of the start of sva. the occurrence of sva was associated with longer duration of use of vasopressor agent and a longer duration stay in icu (+sva group: days, −sva group: days; p = . ). there was no difference in duration of mechanical ventilation and hospital mortality between the two groups. conclusion the occurrence of sva is common in septic shock, poorly tolerated hemodynamically and associated with longer duration stay in the icu and vasopressor need. sepsis myocardial dysfunction isn't necessarily associated to the occurrence of sva. introduction a short term beneficial effect of prone position on cardiac index has been shown in % of ards patients, and was related to an increase in cardiac preload in preload responsive patients ( ) . the aim of this study was to evaluate the long term hemodynamic response to prone position in a larger series of ards patients. patients and methods single center retrospective observational study performed on ards patients hospitalized in a medical icu between july and march . patients included were adults fulfilling the berlin definition for ards, undergoing at least one prone position session, under hemodynamic monitoring by the picco ® device, with availability of hemodynamic measurements performed before (t ), at the end (t ), and after the prone position session (t ). prone position sessions were excluded if they were performed > days after ards onset. the following variables were recorded: demographic, sapsii, ards severity and risk factor, sofa score and cumulative fluid balance at pp onset, delay between ards session and pp session, hemodynamic, arterial blood gas, ventilatory settings, plateau pressure, catecholamine dose and additional treatments. statistical analyses were performed using prone position session as statistical unit and mixed models taking into account both multiple prone position sessions by patient and multiple measurements during a prone position session. p < . was chosen for statistical significance. data are expressed as mean ± standard deviation. results patients fulfilled the inclusion criteria over the study period, totalizing prone position sessions ( ± sessions per patient). patients' age was ± y, % were male, % fulfilled the criteria for severe ards, and sapsii at icu admission was ± . ards risk factors were pneumonia in ( %), aspiration pneumonia in ( %), and sepsis in ( %) patients. duration of prone position sessions was ± h. hemodynamic measurements were performed in pp ± h after pp session onset. at session onset, sofa score was ± , and cumulated fluid balance was . ± . l. vasopressor were used in %, inhaled nitric oxide in %, and neuromuscular blocking agents in % of the sessions. hemodynamic and respiratory parameters before, during and after the prone position sessions are reported in table . cardiac index increased by at least %, decreased by at least % or remained stable in ( %), ( %), and ( %) of the sessions, respectively. as compared to both other groups, pp sessions with significant increase in cardiac index had the following significant differences at t by univariate analysis: lower cardiac index, lower global end-diastolic volume, lower cardiac function index, and lower vasopressor dose. multivariate analysis is under investigation. conclusion prone position is associated with an increase in global end-diastolic volume, reversible after return in supine position that may explain the positive effect of pp on cardiac index observed in ¼ of the pp sessions. introduction make sure that our patient have a good circulatory condition is a daily challenge for the intensivist. one of the therapeutics is fluid and one of his purpose is to increase venous return and then cardiac output. in order to examine that, there are several tools as the transthoracic echocardiogram wich allows the visualisation and the study of the respiratory variability from the inferior vena cava (ivc). unfortunately there are some situations where the ivc visualisation is difficult (obesity, gut surgery, emphysema). the ivc is easily seen by a transhepatic ultrasound in her retrohepatic section. we make the hypothesis that the shape of the ivc could be predictive of fluid responsiveness. we have performed fluid challenge in patients under mechanical ventilation. the need for fluid therapy is the intensivist in charge decision. we performed a echocardiogram and we take two measures of the icv: major axis and minor axis, the icv is measured avec the sus hepatic vena. a elastometry index (ei) is determined which is the ratio of minor axis to minor axis. the fluid challenge is ml of isotonic saline then we perform a new echocardiogram. a tag is written on the patient to take the same ultrasound slice. we retain one increase of % of the cardiac index (ic) as a success of the filling. we exclude the presenting patients a right cardiac insufficiency, an arrhythmia and/or a htap. the statistical analysis is realized with the software r. results between august, and january, we included patients. the average age is of years ( - ), igs of ( - ), ejectionnal fraction of % - ) and the s wave tricuspid is ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the causes of the filling were an oliguria ( %), a low blood pressure ( %), a low cardiac output ( %), a hyperlactatémia ( %) and an other cause in % of the cases. we find a positive correlation between the ei and the increase of the ic, also for the area of the vci and the respiratory variations of the vci (p . ) the other variables are not predictive (bp, e/e' , e/a). the data are summarized in the picture . roc curves has been established ( only % of the journals studied required authors to use stard. a high impact factor and the year of the study were the items associated with a better sqs the presence of a conflict of interest was associated with a lower sqs in univariate analysis. a higher impact factor (> ), was the only independent factors statistically significantly (p = . ) associated with higher sqs in a multivariate regression model. discussion our study showed that the sqs were very low. assessment of a study depends on quality of reporting. blindness and participant sampling are the cornerstone to evaluate such bias as spectrum, verification, review and selection bias of a study, and were unfortunately scarcely reported compared to existing data in diagnosis accuracy reporting. one of the limitation is the years sample of the study. we have planned to continue the analysis for a -year review starting just after the stard publication. conclusion our study showed that several items remain poorly reported. we recommend systematic use of stard criteria in the elaboration and reporting of future studies that evaluates the preload dependence. introduction neurological impairment, i.e. encephalopathy, is commonly observed in patients with decompensated cirrhosis and/or portosystemic shunts admitted in icu. often ascribed to high plasmatic levels of ammonia, encephalopathy could also be induced by drugs or infection, due to altered blood-brain barrier (bbb) permeability. this latter setting is often underdiagnosed and encephalopathy related to hyperammonemia (so called hepatic encephalopathy-he) being pointed out as the culpit of all neurological symptoms in cirrhotic patients. quinolones and betalactamins were recently found in the cerebrospinal fluid of he patients and it has been shown that the expression of efflux pumps, responsible for drugs passing through the bbb, was altered in animal models of he. the purpose of this study was to assess the incidence of neurological impairment, i.e. encephalopathy, in cirrhotic patients hospitalized in discussion overall, we reported a higher rate of lumbar puncture than those reporting in others studies concerning status epilepticus. furthermore the rate of % of pleocytosis directly linked to status epilepticus is slightly higher than in most studies. unfortunately we didn't realize a second lumbar puncture to assess the pleocytosis normalization during the days following the first lumbar puncture. the pathophysiological hypothesis of this phenomenon may be that prolonged/repeated seizures during status epilepticus would induce a blood-brain barrier dysfunction thereby favoring a cerebrospinal pleocytosis. conclusion in our study, % of status epilepticus without infectious or neoplastic origin had a cerebrospinal pleocytosis directly linked to status epilepticus. this pleocytosis was significantly associated with myoclonic seizures and blood leukocytosis. these data may help to interpretation of cerebrospinal fluid pleocytosis during status epilepticus. introduction neurological prognostication from cardiac arrest survivor is a current concern. eeg patterns and nse dosage are two important prognostic factors. nse threshold for prediction of poor outcome appear controversial, in part, because of variability in dosage timing and measurement techniques. synek score is routinely used in our center to classify comatose patients in post cardiac arrest. the aim of this study was to assess the prognostic value of nse and synek classification to predict poor neurological outcome. introduction traumatic brain injury (tbi) is a major public health problem. it is the leading cause of death and disability in young subjects. one of the principles of the tbi management is prevention of secondary cerebral insults including maintaining perfusion and cerebral oxygenation, control of intracranial pressure (icp). an increase in icp above mmhg is associated with poor outcome. cerebral hypoxia can occur with normal level of icp and cerebral perfusion pressure (cpp).monitoring of regional partial pressure of brain tissue oxygen (pbto ) is a safe and reliable method for measuring cerebral oxygenation. a retrospective single-center observational study was conducted between january and december , aimed to study the influence of pbto with severe tbi patients outcome at months through glasgow outcome scale (gos). the hourly values of icp, pbto and cpp were recovered on daily monitoring sheets. we compared two groups according to their gos. during the study period, patients underwent a monitoring icp and pbto . results the mean age was . ± . years. . % were men. the initial glasgow score was . ± . . the mean simplified acute physiology score (saps ii) was . ± . and injury severity score (iss) . ± . . at months, patients had died (gos ). forty patients had a good outcome: gos - (group ). sixteen patients had poor outcome: gos - (group ). in group , there are significantly more pbto hourly values below mmhg at day ( . ± . vs . ± , in group , p = . ); and more pbto hourly values greater than mmhg at day ( . ± . vs . ± . , p = . ). conclusion pbto less than mmhg or greater than mmhg at day is associated with poor outcome at months in the severe tbi. the pbto allows a more individual approach of monitored tbi. none. introduction organ donation in patients after a decision to withdraw life-supportive therapies (wlst) (maastricht condition: m ) have been performed in our hospital since may . we report here main characteristics of donors, data on m procedure and results on renal transplant recipients. patients and methods all potential donors were included in a survey from may to june , according to the french national m protocol defined by the french organ procurement agency (agence de la biomédecine:abm) [ ] .the demographical, clinical and biological characteristics of the donors, the different deadlines and times of the protocol and data of renal transplantation were collected and analyzed. results patients had inclusion criteria. patients were admitted in intensive care unit for cardiac arrest ( %), strokes ( %), traumatic brain injury ( %), ards ( %). of them, procedures ( %) were stopped ( refusals of organ donation, medical contra-indications discovered with additional exams, failure of vessel cannulation, deaths more than h after extubation). kidneys were harvested and transplantations performed ( renal cancer discovered during procurement surgery).the characteristics of the donors, deadlines of the protocol and transplant recipients are reported in the table . conclusion the french programm maastricht offered a new possibility of organ donation in our hospital. thanks to these donors, the number of renal grafts increases and the preliminary results on transplant recipients are encouraging in line with the preliminary report of the abm. nevertheless, it is necessary to follow the transplant recipients and extend the procedure to new centres. in this study, we found some relevant risk factors for microaspiration (age, low score at gcs) consistent with literature on the subject. patients with paralytic agents had less gam which may be due to higher peep, higher cuff pressure and less enteral nutrition because of the severity of the underlying diseases. conclusion this study did not show any increased risk of microaspiration in intubated copd patients, whatever stage of copd. introduction protected specimen brush (psb) is considered to be one of the standard methods for the diagnosis of ventilator-associated pneumonia (vap). to our knowledge, there is no study assessing effect of prior antibiotherapy on direct examination, bacteriological culture and concordance of direct microscopy and culture. patients and methods all consecutive episodes of suspected vap were retrospectively evaluated between january and december in a -bed intensive care unit. patient's characteristics and preexisting conditions were abstracted from the medical charts. after assessment of vap probability using the clinical pulmonary infection score (cpis), psb were performed in patients with a cpis of or more. based on antibiotic treatment in patients when bacteriological specimens were obtained, two groups were defined: no antibiotic group and antibiotic treatment started before psb group. two independent bacteriologists retrospectively reviewed direct examination and culture of psb to assess bacteriological concordance, defined as non-concordant when direct examination and culture were different, concordant when direct examination and culture were similar and partially concordant when either direct examination or culture were comparable but with other microorganisms lacking in one or the other method. results during this -months period, among mechanically ventilated patients, episodes of suspected vap with psb were evaluated. we found % of psb (n = ) performed without antibiotic treatment and % of psb (n = ) performed under antibiotherapy. we found no significant differences in patient's demographics, characteristics, and severity between both groups. patients received antibiotics for the following reasons: aspiration pneumonia (n = ), peritonitis (n = ), vap (n = ), community-acquired pneumonia (n = ), septic shock of unknown origin (n = ), pyelonephritis (n = ), meningitis (n = ), acute pancreatitis (n = ) and others (n = ). the median duration of mechanical ventilation in the antibiotic receiving group and in the group without antibiotics was . days (iqr; - days) and days (iqr: - ), respectively. when psb was performed under antibiotic treatment, direct examination was positive in % (n = ), culture was positive in % (n = ) and those methods were concordant, non concordant and partially concordant in % (n = ), % (n = ) and % (n = ), respectively. on the other hand, when psb was performed without antibiotics, direct examination was positive in % (n = ), culture was positive in % (n = ) and those methods were concordant, non concordant and partially concordant in % (n = ), % (n = ) and % (n = ), respectively. in univariate analysis, we found a significantly higher proportion of negative direct examination and negative culture in the antibiotic group (p > . ). moreover, these methods were significantly more frequently concordant (p = . ), with a higher rate of both negative microscopic exam and culture when compared to the no antibiotic group ( %, n = vs %, n = ). surprisingly, among the patients previously treated with antibiotics with positive culture, % (n = ) of the microorganisms showed antibiotics sensitivity. discussion whether prior antibiotic treatment may induce false negative of false positive treatment is a well-recognized phenomenon, the precise effect of antibiotics on direct examination and quantitative culture is not well assessed in vap. moreover, despite recent development of clinico-radiological score, diagnosis of vap remains difficult, with no gold-standard. therefore, bacteriological guided therapy is of particular importance. we found psb realization under antibiotic treatment is associated with a lower rate of positive direct examination and culture and suggest performing these bacteriological samples without antibiotherapy. some authors have suggested lowering the diagnostic threshold point of this bacteriological technique in order to preserve its accuracy. however, we can postulate that microorganisms responsible of superinfection in mechanically ventilated patients treated with antibiotics may be resistant and therefore the psb could be positive. conclusion in patients with a high pre-test probability of ventilatoracquired pneumonia, recent introduction of antibiotics significantly reduced the diagnostic accuracy of protected brush specimen by reducing rates of positive direct examination and culture. further studies should evaluate if antibiotic discontinuation may revert this effect. ann. intensive care , (suppl ): we have had non conflict of interest in this study. results we included patients in the phase and patients in the phase . baseline characteristics of patients were similar in both groups. compliance with all the measures has been improved between the two period from to . %. the incidence density decreased from . to . vap per ventilator days between observational and interventional period, but the all-cause mortality was almost equal in the groups ( . vs. %). discussion with the implementation of our bundle, observance of the team were improved in the second group, compared to the first and the incidence density decreased from . to . vap per ventilator days between both period. this result is consistent with the littérature. sure enough, many studies show the same effect of vap prevention with a decrease of nearly % of the incidence density of vap, after implementation of a «ventilator -bundle [ ] . conclusion the implementation of a "ventilator bundle, " has significantly reduced the incidence of vap in our service. in the contrary, our study failed to demonstrate a reduction in mortality. introduction with an increasing incidence and high mortality rates, sepsis is a public health issue. there is growing evidence that sepsis induces long lasting alterations of transcriptional programs through epigenetic mechanisms that may lead to protracted inflammation, organ failure, sepsis-induced immune suppression (siis), secondary infections and death. we hypothesized that epigenetic changes contribute to the pathophysiology of siis. to test this hypothesis, we studied the effects of histone deacetylases (hdac) inhibition with trichostatin a (tsa) in a double-hit murine model of siis and secondary pneumonia. materials and methods c bl/ mice were treated with tsa ( mg/ kg ip) or saline serum (ctl) min before induction of sepsis by cecal ligation and puncture (clp). surviving mice underwent intratracheal instillation of . × cfu of pseudomonas aeruginosa days after clp. we evaluated the effect of tsa on survival and cellular responses to the primary and secondary infections. cellular responses in the blood, spleen and bal were assessed by flow cytometry after clp (days , & ) and after pneumonia ( & h). we also studied lymphocyte apoptosis and dendritic cells (dc) expression of cd , cd , and mhcii. bacterial clearance was assessed in the bal and in the blood and h after pneumonia. continuous variables represented as mean ± sd were compared using student t test. kaplan-meier curves were compared by the log rank test. p < . indicated statistically significant differences. results whereas treatment with tsa did not change survival after clp, tsa improved survival after tracheal instillation of p. aeruginosa (p = . , fig. ). tsa-treated mice had significantly higher absolute dc, t and b-lymphocytes counts with reduced lymphocyte apoptosis after clp. four hours after secondary pneumonia, tsa-treated mice had significantly higher dc counts and improved bacterial clearance in the bal, with reduced systemic dissemination of p. aeruginosa. conclusion hdac inhibition with tsa improves survival in our murine model of secondary pneumonia, improves bacterial clearance and attenuate cellular features of siis. these results suggest that sepsisinduced epigenetic changes contribute to the advent of siis. comprehensive characterization of epigenetic changes associated with siis might allow us to identify new therapeutic targets to reprogram immune cells in sepsis and avoid siis. length of icu stay was ± days. patients acquired nis ( . % bsi, . % pneumonia, . % cri and . % uti. there was no bacteriological documentation of ni in . % of cases. nis occured days post burns. the most three isolated pathogens were: acinetobacter spp. ( %), p. aeruginosa ( . %) and extended spectrum betalactamase-producing enterobacteriaceae ( %). the most frequently administered antibiotics were polymyxin/carbapenem/teicoplanin combination ( %), polymyxin/carbapenem combination ( %) and carbapenem/tigecycline combination ( %). in our study, mortality rate was %. conclusion nosocomial infection occured in . % of cases in burn patients, caused by acinetobacter spp, p. aeruginosa and enterobacteriaceae blse. so, eradication of infection in burn patients require effective surveillance and infection control in order to reduce mortality rates, length of hospitalization and associated costs. introduction infection of the lower respiratory tract is the most common cause of infection in intensive care unit (icu) ( ) . although the attributable mortality of ventilator associated pneumonia remains debated, the recurrence of these infections is always associated with a significant morbidity ( ) . staphylococcus aureus methicillin-sensitive (sams) is one of the most frequently germs involved in icu pneumonia especially in trauma patients. the aim of the study was to establish the risk factors associated with microbiological treatment failure of pneumonia, caused by sams. materials and methods we retrospectively identified patients who developed a first episode of ventilator associated pneumonia caused by sams during a years-period ( - ). the primary end point was the microbiological treatment failure defined as a second episode of pneumonia caused by sams corresponding to either a persistent or a recurrence of the pneumonia (fig. ) . the primary aim of the study was to identify factors associated with a treatment failure, the secondary objective was to identify factors associated with the occurrence of second episode (i.e. persistent, recurrence, superinfection and/or relapse of pneumonia caused by any bacteria) during or after treatment of the first episode caused by sams. definition of outcomes was based after analysis of current concepts available in the literature. factors associated with primary and secondary objectives in univariate analysis (p-value < . ), or clinically relevant ones, were entered in a multivariate logistic regression. the final selection was performed using the stepwise selection based on the akaike criterion. results fifty-nine patients ( . %) developed a second episode of pneumonia and among them, ( . %) were considered as a microbiological failure. in a multivariate analysis, the association of oropharyngeal flora (fop) with the sams (or, . ; % ci, . - . ; p = . ) and the need of emergency surgery (or, . ; % ci, . - . ; p = . ) were predictive of a microbiological failure. empirical antibiotic therapy with amoxicillin-clavulanic acid (or, . ; % ci, . - . ; p = . ) and performing emergency surgery (or, . ; % ci, . - . ; p = . ) were predictors of a second episode of pneumonia caused by any bacteria. conclusion in this retrospective, monocentric study, the co presence of orophryngeal flora and the need of emergency surgery were associated with microbiological failure of pneumonia caused by sams in icu. introduction ventilator-associated pneumonia is a major iatrogenic problem since it is a cause of hospital morbidity, mortality and increase of health care costs. it has been studied many times, but data's revision is always necessary. our study aimed to describe epidemiology of ventilator-associated pneumonia and identify local causative pathogens. we carried out a prospective study in an intensive care unit. were included patients intubated for more than h, from april to may , and presenting signs of ventilator-associated pneumonia (fever, abundant and purulent secretion, increase of fio greater than . , signs on chest-x ray) with positive culture of endotracheal aspirate. were excluded patients with germ colonization. results a total of patients were ventilated for more than h. among them thirty-four patients aged of ± . years presented episodes of ventilator-associated pneumonia (that is . ± . episodes per patient). the mean sofa score was . ± . . the main reasons of mechanical ventilation were loss of consciousness secondary to poisoning ( %), respiratory distress ( %) and status epilepticus ( %). the mean duration of stay was . days with extremes at and days. the average time between hospitalization and suspicion of ventilator-associated pneumonia was . ± . days. the average value of the clinical pulmonary infection score at suspicion was ± . . the average time between recurrences was . days with extremes at and days. the culture of endotracheal aspirate identified two pathogens in %. it reveled acinetobacter baumanii in % in which % were imipenem resistant, pseudomonas aeroginosa in %, klebsielle pneumoniae in %, staphylococcus fig. see text for description aureus methicillin resistant in %. extended spectrum β-lactamases bacteria were found in % and carbapenemases producers in %. empirical antibiotherapy was always association of imipenem and colistin. it was necessary to adapt it to antibiograms in / . ventilator-associated pneumonia was complicated by septic shock in % and acute respiratory distress syndrome in %. patients evolved to healing in % of episodes (n = ), to superinfection in % (n = ) and to death in % (n = ). pseudomonas aeruginosa was the most frequent germ in superinfection ( / ) , acinétobacter baumanii was the most pathogen associated to death ( / ). conclusion ventilator-associated pneumonia is an iatrogenic disease that threatens lives. it's in part avoidable. preventive measures have to be implemented to reduce its frequency, consequences and costs. introduction during mechanical ventilation, mismatch between respiratory muscles activity and the assistance delivered by the ventilator results in dyspnea and asynchrony and is commonly observed in intensive care unit (icu) patients. proportional assisted ventilation (pav) is a ventilatory mode that adjusts the level of ventilator assistance to the activity of respiratory muscles estimated by an algorithm. to date, pav has been mostly studied in patients without severe dyspnea or asynchrony. we hypothesized that, compared to pressure support ventilation (psv), pav will prevent severe dyspnea or asynchrony. patients and methods were included icu mechanically ventilated patient exhibiting severe dyspnea or asynchrony with psv. three conditions were successively studied: ) psv on inclusion (baseline), ) psv after optimisation of ventilator settings in order to minimize dyspnoea and asynchrony (optimisation), and ) pav. ten-minutes recording were performed with each condition. the intensity of dyspnea was assessed by the visual analogic state (vas, only in patients able to communicate) and by the intensive care respiratory distress operating scale (ic-rdos) for all the patients. the electrical activity (emg) of extradiaphragmatic inspiratory muscles was measured. the fig. bayesian nma with random effect prevalence of asynchrony was quantified by the visual inspection of the airway flow and pressure traces. results patients were included, % male, aged [ - ] years, saps [ - ], mechanically ventilated for [ ] [ ] [ ] [ ] [ ] [ ] days. the tidal volume (tv) was higher in the optimisation and pav than in the basal condition (table ). the respiratory rate(rr) was lower with pav than in the other conditions. the dyspnea-vas was lower with optimisation and pav than with the basal conditions. the ic-rdos was lower with pav than with the two other conditions. the asynchrony index was lower with pav than with the two other conditions. parasternal emg activity was lower with pav and optimisation (fig. ) . conclusion in icu patients receiving mechanical ventilation with psv and exhibiting severe dyspnea or asynchrony, the optimisation of ventilator settings with psv and the pav mode decrease in the simiar way the severity of dyspnea and the prevalence of patient-ventilator asynchrony. introduction in spite of recent research and progress in weaning protocols, extubation failure still occurs in - % of patients and is associated with poor outcomes, with a mortality rate of - %. many risk factors for planned extubation failure have been suggested, including hypercapnia at end of spontaneous breathing trial (sbt). however, performing arterial blood gases at the end of sbt is not routinely recommended whereas etco may be routinely monitored during a low pressure support sbt. the aim of this prospective observational study was to determine the clinical usefulness of etco to predict extubation failure. patients and methods we recorded clinical data and etco during a successful h low level pressure support sbt (at the beginning, after min and at the end of the trial). patients ventilated through tracheostomy and unplanned extubations were excluded. extubation failure was defined as death or the need for reintubation within h ( ) after extubation; this delay was prolonged to days ( ) in case of noninvasive ventilation after extubation, which was systematic in older patients or those with cardiorespiratory disease, as per our weaning protocol. multivariable logistic regression analysis was performed to identify independent variables associated with extubation failure. results one hundred and fifteen ventilated patients were enrolled in our study from july to june . the median age of these patients was [ - ] years, their median simplified acute physiology score (saps) ii was [ - ] points and . % (n = ) were female. seventeen ( %) patients had chronic obstructive pulmonary disease. reintubation rate was % (n = ). etco at other time points as well as its changes during the sbt were also similar between groups. the three variables predicting extubation failure in the multivariable logistic regression model were a past medical history of cirrhosis, acute respiratory distress syndrome before weaning and lower minute ventilation at the end of sbt. conclusion etco during a successful sbt seems useless to predict outcome of extubation. introduction airway management in intensive care unit (icu) patients is challenging [ ] . "airway failure", defined as the inability to breathe without endotracheal tube, differs from "weaning failure", defined as the inability to breathe without an invasive mechanical ventilation. however, most of the studies assessing predictive factors of extubation failure did not separate airway from weaning failure. we aimed to describe incidence of extubation failure in critically ill patients, separating for the first time airway from weaning failure, in a prospective multicenter observational study. patients and methods a prospective, observational, multicenter study was conducted in french icus. all adult patients consecutively extubated in icu were included. an ethics committee approved the study design (code uf: , register: -a - ). the study was registered on clinicaltrials.gov (identifier no.nct ). clinical parameters were prospectively assessed before, during and after extubation procedure. extubation failure was defined as the need to reintubate less than h after extubation. extubation failure could be due to airway failure, weaning failure or mixed airway and weaning failure. results from december to may , intubation-procedures were studied in patients from centers. patients ( . %) were intubated twice. the median number of intubation-procedures included by center was . the flow chart of the study is shown in fig. . incidence of extubation failure was . % ( of intubation-procedures). incidence of airway failure, weaning failure and mixed failure were respectively . % ( of ), . % ( of ) and . % ( of ). conclusion extubation failure at h occurred in . % of the extubation procedures recorded, % due to airway failure, % to weaning failure and % to mixed airway and weaning failure. specific risk factors will be determined using this multicenter database. introduction acute on chronic liver failure (aclf) have been recently defined by an acute decompensation of a chronic liver disease associated to organ failure and a high mortality rate. few authors reported on the use of total plasma exchange (tpe) in patients with the current definition of aclf. the aim of this pilot study was to evaluate the efficiency and safety of tpe in critically ill cirrhotic patients admitted with aclf in the icu. patients and methods a prospective cohort of cirrhotic patients admitted to the icu between february and february . tpe was performed using a plasma filter (tpe , hospal ® ) on a cvvhdf machine (prismaflex ® , baxter ® ) connected to the patient with a femoral double lumen f catheter. the plasma volume exchanged per session was . - . of the total plasma volume. ratio and type of fluid replacement were % with % albumin solution followed by % with fresh frozen plasma. clinical and biological parameters, and the following scores meld, sofa, clif-sofa, clif-of and child pugh were evaluated prior, after tpe session and days distant of treatment. results seven male patients with a mean age of . ± . years comprised the study and had a total of tpe sessions. the etiology of cirrhosis was alcoholic (n = ) or post-hcv (n = ). the reasons of aclf were acute alcoholic hepatitis (n = ), variceal bleeding (n = ) and sepsis (n = ). prior to tpe, the mean scores of sofa, clif-sofa, clif-of, meld and child-pugh were respectively . , , . , . and c . . mean total bilirubin prior and after tpe sessions was reduced from . ± . µmol/l to . ± . µmol/l (reduction of . %; p = . e− ); at day , mean total bilirubin was still lower at ± µmol/l (p = . ). mean inr prior and after tpe improved from . ± . to . ± . (reduction of inr of . %, p = . e− ) and at day of treatment at ± . (reduction of %, p = . ). mean ggt levels reduced by . % (p = . ). mean platelet counts ( . ± . g/l) reduced by . % (p = ns). the probability of survival at , and days was . , . and . %. one patient was transplanted and still alive. tolerance during sessions was good similar to cvvhdf. two side effects related to the femoral catheter were observed (bacteremia and hemorrhagic shock post catheter ablation). conclusion this preliminary study of tpe in aclf showed a marked reduction of liver enzymes and improvement in coagulation parameters with a relative good safety. a specific caution should be undertaken regarding catheter related complications. tpe worth to be fig. flow chart of the free-rea study introduction extubation is a key moment for the patient on his way to recovery. extubation failure concerns - % of icu patients and is closely linked to nosocomial pneumonia. the practice concerning enteral feeding interruption at time of extubation has not been investigated. fasting before extubation may prevent aspiration and development of nosocomial pneumonia. thus, fasting and gastric content suctioning before extubation may be reasonably considered as a mean to reduce this burden. fasting before extubation may prevent aspiration and development of nosocomial pneumonia. thus, fasting and gastric content suctioning before extubation may be reasonably considered as a mean to reduce this burden. however, fasting, as recommended before elective general anesthesia is likely to be ineffective in the setting of extubation in the icu, due to patients' gastroparesis and prolonged gastric stasis. beyond the potentially unnecessary burden in terms of paramedical workload, fasting may have some side effects such as caloric deficit, hypoglycemia, or delayed extubation. given the current lack of objective data concerning the clinical practice of feeding/fasting and gastric tube suctioning before extubation in the icu, we undertook this descriptive study to assess current practice. materials and methods we conducted a retrospective, multicenter study in eleven intensive care units in the west of france over a month timespan. all patients extubated were included and data about enteral feeding during the peri-extubation period as well as extubation failure and nosocomial that pneumonia occured within days were recorded. data observed in the eleven participating centers were completed with a short email survey concerning declarative practice performed among intensive care units. results during the study period, patients were included. overall, patients ( %) failed extubation and needed reintubation within the days following planned extubation. pneumonia was significantly more frequent reintubated patients than the other ( vs. %, p < . ). hundred patients ( %) received enteral feeding at the time of extubation. compared to patients who did not receive enteral feeding, those patients had a higher disease severity (sapsii score , [ ; ] vs. [ ; ], p < . ; longer duration of mechanical ventilation [ ; ] vs. . [ ; ] days, p < . ). accordingly, those patients had a higher rate of extubation failure ( vs. %, p = . ) and pneumonia ( vs. %, p = . ). among the patients receiving enteral feeding, fasting was implemented before extubation for patients ( %). similarly, the incidence of pneumonia was not different between groups (n = ( %) vs. n = ( %), p = . ). after extubation, the fasting patients experienced a longer delay until feeding resumption as compared to non-fasting patients ( h [ ; ] vs. [ ; ] ), but this difference did not reach statistical significance. overall gastric content suctioning before extubation was not commonly performed; before extubation: % of the fasting patients and % of the non fasting patients. among the participating centers, while some centers imposed a fasting period before extubation to all their patients, some did it infrequently. however, no center never imposed fasting, illustrating between and within center heterogeneity. this heterogeneity was confirmed on the larger scale declarative email survey ( % response rate amont units) which showed that only % of the units had a written standardized operational procedure for extubation. survey respondents reported to practice fasting before extubation "always", "frequently" and "never or rarely" in respectively , and % of cases. conclusion both practices, fasting as well as pursued nutrition until extubation are commonly performed in icus, with little standardization of practice. safety seems equivalent, as no clinically significant difference in terms of reintubation rate and pneumonia were observed. thus, the equipoise condition appears met to undertake a trial evaluating feeding strategies in the peri-extubation period. introduction noninvasive ventilation (niv) has become a cornerstone for the supportive therapy of acute respiratory failure (arf). survival benefits in chronic obstructive pulmonary disease (copd) and cardiac patients have been demonstrated. although arf and copd patients are at risk of malnutrition that adversely affects patient outcomes, few data are available regarding the management of nutritional support in non-invasively ventilated patients. we sought to describe nutritional management in patients receiving niv as the first line therapy for arf. secondary objectives were to assess the impact of early nutrition use on the need for invasive mechanical ventilation, occurrence of icuacquired pneumonia, length of stay, and death. patients and methods we conducted an observational study from the multicenter french database fed by french icus. our institutional review board approved this study. adult medical patients admitted to the icu and receiving niv for more than days were included. exclusion criteria were patients admitted after surgery, readmitted in icu, patients with neuromuscular disease and treatment-limitation decisions on admission. four groups of patients were defined according to nutrition received during the first days of niv: ( ) no nutrition; ( ) enteral nutrition: patients who received enteral nutrition with or without parenteral nutrition; ( ) parenteral nutrition only ( ) oral nutrition only. the impact of nutrition on day- mortality was assessed through the use of a cox model adjusted on clinically relevant covariates. the impact of nutrition on other secondary end-point i.e. icu-acquired pneumonia occurrence, need for invasive mechanical ventilation were assessed using a fine & gray models. patients were censored after days of follow-up. choice among collinear variables was performed considering clinical relevance, rate of missing variables and reproducibility of definitions. results were given as hazard ratio (hr) for cox models and subdistribution hazard ratios (shr) and % confidence intervals (ci). the impact on duration of stay was estimated by a multivariate poisson regression. p values less than . were considered as significant. statistical analysis was performed using sas . (cary, nc). results during the study period, , patients were included in the database and met inclusion criteria. among them, received no nutrition; received enteral nutrition, received parenteral nutrition only, and received oral nutrition only. overall, patients developed icu-acquired pneumonia ( %), required invasive mechanical ventilation ( . %) and died before day- ( %). median length of stay was days [ ; ]. after adjustment for confounders, type of nutrition support was associated with an increase day- mortality (p = . ). compared to oral nutrition, enteral nutrition was associated with an increase day- mortality [shr . , % ci . - . ; p = . ] whereas parenteral nutrition and no nutrition did not influence this outcome. the type of nutrition was not associated with the occurrence of icu-acquired pneumonia (p = . ). however, patients who received enteral nutrition experienced more frequently icu-acquired pneumonia [shr = . , % ci . - . ; p = . ] as compared to oral nutrition patients. ventilator free days within the days were negatively associated with the type of nutrition (p < . ). compared to oral nutrition, parenteral and enteral nutrition were negatively associated with ventilator free days within the days [rr per day = . , % ci . - . ; p < . and rr per day = . , % ci . - . ; p < . ]. delta paco measured between the first days was not associated with any type of nutrition. conclusion more than half the patients receiving niv were fasting within the first two niv days. oral nutrition was prescribed for onethird of them and was well tolerated. lack of feeding or underfeeding had no impact on mortality and ventilator free days within the days. however, enteral nutrition was associated with an increased occurrence of icu-aquired pneumonia and a higher mortality rate. was high, caloric debt during temporary ecls was low in comparison with previous results [ ] . overnutrition was frequent in the nec group and would justify implementation of nutrition protocol. incidence of gi intolerance remains frequent and could justify systematic used of motility agents with introduction of en. conclusion enteral nutrition in patients treated with temporary extracorporeal life support is feasible and may be improve with systematic motility agents and implementation of nutritional protocol. introduction cardiac surgery with cardiopulmonary bypass (cpb) is associated with a generalized inflammatory response with concomitant immune paresis which predisposes to the development of postoperative infections and sepsis ( ) . lymphocytes are essential agents of innate and adaptive immune responses during infections or inflammation processes. lymphopenia has been associated with immune dysfunction during septic shock, and it has been shown that low absolute lymphocyte count was predictive of postoperative sepsis ( ) . furthermore, impaired lymphocyte function probably occurs after cpb. thus, we investigated mechanisms involved in postoperative lymphopenia and impaired lymphocyte function after cpb. the aims of this study were: ) to describe a potential relationship between lymphopenia and occurrence of postoperative infections. ) to demonstrate that cpb induces lymphocytes apoptosis. ) to demonstrate that cpb impaired lymphocyte function (ability to proliferate). ) to demonstrate that il- , pd-l (programmed cell death ligand ) and indoleamine , -dioxygenase (ido) could be interesting targets to restore lymphocyte ability to proliferate after cpb. patients and methods blood cell counts with differentials obtained within the first postoperative week were analyzed in patients undergoing cardiac surgery in . postoperative lymphopenia was defined as a lymphocyte count < . × cells l − . postoperative infections were defined following cdc criteria. study procedures: the following analysis were performed before (t ) and h after (t ) cardiac surgery with cpb: lymphocyte apoptosis; t-cell proliferation ability following polyclonal stimulation; hla-dr and pd-l expression on monocytes; plasma ido activity and il- levels; and the ability of lymphocytes to undergo a clonal proliferation when stimulated using specific inhibitors of il- and ido. the study was approved by our local ethics committee. patients were informed of the observational nature of the study and gave their consent. . early lymphopenia after cpb was associated with the occurrence of postoperative infection: postoperative infections occured with a median delay of days. patients who developed postoperative infections had a significantly lower lymphocyte count at day , day and day than patients without postoperative infections. . cpb induced lymphocyte apoptosis and decreased t-cell proliferation ability. . cpb during cardiac surgery decreased mhla-dr expression. . cpb increased ido activity, pd-l expression and il- plasma levels. . il- or pd-l inhibition of inhibition could restore ability of lymphocytes to proliferate, although ido inhibitors did not show any effect. we provided new evidences that cpb induces immunosuppression. we also demonstrated that il- and pd-l could be interesting targets to restore ability of lymphocytes to proliferate. as maintaining mv during cpb decreased plasmatic levels of il- , our study brings new evidences that ventilator strategies could be of interest to decrease postoperative infections. respectively . % (n = ), . % (n = ) and . % (n = ) of the included patients. mortality was of . % in the overall population (n = ) and was higher in neutropenic patients ( . vs. . % in non-neutropenic patients; p < . ). neutropenia was independently associated with poor outcome when adjusted for underlying malignancy, allogeneic stem cell transplantation and severity as assessed by organ support (or . ; % ci . - . ). mortality decreased progressively over time in both non-neutropenic (from to %; p < . ) and in neutropenic patients (from to %; p < . ). when adjusted for confounders, admission during a more recent period was independently associated with favourable outcome and did not change the final model. conclusion this preliminary analysis suggests a meaningful survival in neutropenic critically ill cancer patients despite an independent association between neutropenia and mortality. additional analyses are on-going in order to adjust for study weight, heterogeneity across studies, assess the influence of neutropenia duration or g-csf use, and confirm the influence of neutropenia in a predefined subgroup of patients. introduction candida bloodstream infections (cbi) are frequent and increasing in hospitalized patients, especially in intensive care units. considering the results of some experimental in vitro and animal studies, it seems that yeasts belonging to candida genus are able, so as to survive, to modulate the immune response of the host by guiding t cells polarization to th profile. th and th cytokines are known to be involved in host defense against cbi. however, these data are mainly experimental or collected after candidemia. the aim of this study is to precise kinetic of cytokines network during human cbi. this was an ancillary study of an institutional project dedicated to pathophysiology of candidiasis. we have included patients with candidemia and controls ( matched hospitalized controls and healthy subjects). the sera of cases were gathered before (almost days before), during and after the isolation of yeasts from blood culture, defined as day (d ). quantitative analysis of cytokines by luminex ® technology and of ( , )-β-d-glucans by fungitell ® test were performed on samples. the amplitude of th profile response was expressed by summing the amount of the most relevant cytokines for th , th and th profiles, in pg/ ml. for each patient, the highest level of response was considered as %. results are expressed for the population by means of the results. we then performed univariate analysis (fischer exact test for qualitative variables, mann-whitney and wilcoxon test for quantitative variables, spearman for correlation; graphpad prism v software) and a multidimensional analysis by principal component analysis (pca; igorpro software). results patients with candidemia exhibited an increase in proinflammatory cytokines (ifnγ, tnfα and il- ), in comparison with the anti-inflammatory cytokines (il- and il- ) before d (p = . ) in univariate analysis. the ratio between mean values reverses at d and d (p = . ) and the increase of th response level from d to d is correlated to the decrease of th response (r = − . ; p = . ) in univariate analysis and pca. a pro-inflammatory response (th ) is associated with a reduced mortality (rr = . [ . ; . ]) and with a lower β-d-glucans levels (p < . ). discussion we describe here a dynamic cytokine profiles in response to candidemia. pro-inflammatory response predominates before d and reverses after. this is contradictory to the postulate that an antiinflammatory background could predispose to invasive candidiasis in icu patients and exhibiting a "post-infectious immune suppression conditions". but the relative deficiency in th response compared to simultaneous anti-inflammatory cytokines secretion observed after cbi is in accordance with experimental data, suggesting the modulation of the immune response by candida. the link between cytokinic profile and mortality can also raise the hypothesis of an influence by genetic factors on the regulation and direction of the immune response and so, the existence of a high-risk population. conclusion these data suggest a relation between candida and the orientation of the immune response towards a pattern deleterious for the infected host. this could allow to determine the most relevant cytokines varying during cbi. they could be used as biomarkers to identify the patients who could benefit from an early treatment in a preemptive targeted therapeutic strategy. these data will be paralleled to genetic background and to circulating candida derived molecules to precise the relative part of the host and the pathogen in this complex interaction. introduction lung ultrasound is widely used in intensive care, ermergency and pneumology medicine, for assessing acute respiratory pathologies. it is noninvasive, radiation free and rapidly available at the patient's bedside and provides an excellent accuracy. so, lung ultrasound may be an interesting tool for the physiotherapist as it allows to assess with more accuracy the patient improving the chest physiotherapy indication and monitoring ( ) . as far as we are aware, no study has evaluated the impact of lung ultrasound on clinical-decision making by physiotherapists in the use of chest physiotherapy. this case report highlights the lung ultrasound interest in chest physiotherapy in patient with lung consolidation. patients and methods this was a case report written following the recommendations of the care guideline ( ). the case was a -years-old female patient, non intubated, hospitalized in a respiratory icu. she was hypoxemic (pao = mmhg and sao = %), with dyspnoea at rest and an increasing radiological opacity at the right lung base. hypoxemia was the indication for physiotherapist referral. at the clinical examination, the physiotherapist's findings were: decreased mobility, dullness and abolished vesicular sound at the base of right hemithorax. this clinical examination and chest x-rays analysis allowed the physiotherapist to propose several clinical hypotheses: pleural effusion, obstructive atelectasis or pneumonia. the chest physiotherapy treatment differs according to the type of lung deficiencies. for example, the physiotherapist must to refer the patient to the medical staff in case of pleural effusion or may implement hyperinflation technique in case of obstructive atelectasis. determining the nature of lung deficiencies is essential to provide the more suitable therapeutic strategy. so, the physiotherapist decided to perform a lung ultrasound examination to retain the more likely hypothesis. results ultrasound examination performed by the physiotherapist highlighted the presence of a lung consolidation at the infero-lateral and posterior parts of the right lung with a pneumonia pattern: presence of tissue-like sign, shred sign, dynamic air bronchogram and fluid bronchogram. the medical staff implemented antibiotic treatment. the ultrasound findings guided the physiotherapist to choose chest physiotherapy technique improving the alveolar recruitment: nearly prone position (left side down) and continuous positive airway pressure during min. the patient response to the treatment was monitored by ultrasound and showed a decrease of the lung consolidation size and apparition of b lines, meaning a gain of lung aeration. these findings were associated with spo improvement but without decrease of dyspnoea. discussion lung ultrasound allowed the physiotherapist to precise the nature of the radiological lung opacity. as it is more accurate than clinical examination or chest x-ray, this suggests a more suitable choice of chest physiotherapy techniques than conventional clinical decision-making process. ultrasound findings suggested a positive response to the chest physiotherapy treatment. the apparition of re-aeration signs (b lines, decreased consolidation size) showed a short-term efficacy of the chest physiotherapy treatment. this allowed the physiotherapist to continue the treatment during week and obtain a substantial clinical improvement. conclusion the use of lung ultrasound in the clinical decision-making process may help the physiotherapist to choose with more accuracy the therapeutic strategy. moreover, it allows to monitor the treatment in real-time and assess the patient's response. the use of this tool may allow the physiotherapist to determine the optimal indications for chest physiotherapy and thus avoid unnecessary or inappropriate treatments. introduction critical illness together with immobilization have deleterious effects on patients outcome, especially in the presence of sepsis. increased muscle catabolism and membrane inexcitability reduce muscular mass and impair function within the first days after sepsis onset ( ). early mobilization could potentially limit muscle wasting and functional impairment in this population. the purpose of this study was to test whether exercise during the early phase of sepsis is safe and beneficial and to which extent it can limit skeletal muscle protein catabolism and preserve function. patients and methods adult patients admitted with the diagnosis of severe sepsis were included and randomly allocated to two groups; ) control group (ctrl-g): manual passive/active manual mobilization twice a day or ) experimental group (exp-g): additional two times min of passive/active cycling exercise. both groups benefited from a reduced sedation, adjusted nutritional intake and bed to chair transfer as soon as possible. skeletal muscle biopsy and electrophysiological testing were realized at day- and day- . muscle histology, biochemical and molecular analyses of anabolic/catabolic and inflammatory signalling pathways were performed. a group of four healthy subjects was used to obtain non pathological values. hemodynamic parameters and patients perception were collected during each session. results twenty-one patients were included, however died before the second muscle biopsy. ten patients in ctrl-g and nine in exp-g were finally analysed. muscle fibre cross sectional area (µm ) was significantly preserved by exercise (relative changes were ctrl-g: − ± % vs exp-g: ± %, p = . ). markers of catabolic systems were highly increased during sepsis compared to healthy subjects and reduced in both groups days after admission. however the reduction in mrna (relative change) tended to be more important in exp-g: murf- (ctrl-g: − ± % vs exp-g: − ± %, p = . ), mafbx (ctrl-g: − ± % vs exp-g: − ± %, p = . ), lc b (ctrl-g: ± % vs exp-g: − ± %, p = . ) and bnip (ctrl-g: ± % vs exp-g: − ± %, p = . ). anabolic and inflammatory markers were not affected by exercise. electrophysiological testing, including direct muscular stimulation, was abnormal on day- in of evaluated patients. since only a limited number of patients could be reassessed a second time, comparison between groups was not possible. in general, all activities were well tolerated by patients with no adverse events. the pulmonary auscultation is used by respiratory therapist (rt) to evaluate the efficiency of a treatment. listen to the noises coming from the primary bronchi (pb) is important because it is the place where secretions can be accumulated. therefore, it is crucial to know exactly where to place the stethoscope's chestpiece on the chest. few studies have analyzed the chest area where the pb were located. our hypothesis is that pb are localized on a line that joins axillary fossa (bi-axillary line: bal). the aim of our study is to evaluate the probability to find the primary bronchi by analysis of chest radiography. patients and methods a retrospective study was performed by analysis of chest x-ray using the software: tm reception ® , which allows precise measures to the tenth of millimeter. all the x-rays were made on confined to bed patients hospitalized within intensive care unit, internal medicine and abdominal surgery rooms. the following measures (in mm) were made between: the exclusion criteria were: bmi < . kg/m and bmi > kg/m , scoliosis, minor patient, lack of visibility of one of the axillary fossa, lack of visibility of pb, clavicular asymmetry, kyphosis, lack of symmetry in the shot, atelectasis and pneumothorax. statistics: normality test: ks. mean values are expressed with their sd and % ci. discussion in this study, we performed analysis of chest x-rays of bedridden patients and we demonstrated that it is possible to localize easily, on either side of the bs, the right and left pb at ± mm distance (lp) above a line joining axillary fossa. this study constitutes a new tool for the rt who, by using stethoscope with a chestpiece of cm surface area, will be able to listen to noise coming from pb. conclusion the data presented herein (fig. ) show that right and left pb are located at a mean distance of (± ) mm and (± ) mm above the bal, on both sides of the bs. the bal represents thus an easy and precise mode to detect right and left pb by bedridden. finally, the distance between the hyoid bone and the sc is about cm. as the pb are located after the bifurcation, this information constitutes another useful way for the localization the right and left pb by bedridden patient. introduction critically ill patients frequently develop muscle weakness, which is associated with prolonged intensive care unit and hospital stay ( ). this randomized controlled trial (clinical trials nct ) was designed to investigate whether a daily training session using a tilt table, started early in stable critically ill patients with an expected prolonged icu stay, could improve strength at icu and hospital discharge compared to a standard physiotherapy program. the study protocol was approved by an ethics committee and informed consent was obtained from all patients. patients admitted in adult icu of marie lannelongue hospital, france, who were mechanically ventilated for at least days were included. exclusion criteria were cerebral or spinal injury, pelvic or lower limb fracture. patients were assessed each day for temporary contraindications for mobilization out of bed (rass score <− or > ; hemodynamic instability; a continuous intravenous dose of epinephrine/ . no significant difference was observed in terms of mrc score or in terms of pts with or without weakness (mrc > ) at icu or hospital discharge. however, the number of pts with weakness was significantly higher in the group before tilt mobilization, suggesting a more rapid improvement in the tilt group. the icu and hospital lengths of stay were not different between groups. discussion the prevalence of muscle weakness in our population is high before mobilization ( . %, % ci . - . ), is still . % at icu discharge but represents only ~ % at hospital discharge. this low hospital discharge prevalence is probably related to the early and intense physiotherapy in both groups, which may explain our inability to demonstrate superiority of the addition of tilt table positioning, although a faster recovery is suggested. conclusion training sessions using a tilt table, in addition to early and intense physiotherapy did not improve muscle strength evaluated using mrc score in surgical icu patients with muscle 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coordination prélèvements organes s reference . conditions à respecter pour réaliser des prélèvements d'organes sur les donneurs décédés après arrêt circulatoire de la catégorie iii de maastricht dans un établissement de santé. agence de la biomédecine. version n° mai crcl by cockroft-gault, mean (ml/mn delayed graft function, n (%) ( . %) réanimation médico-chirurgicale infectious diseases society of america. guidelines for the management of adults with hospital acquired, ventilator-associated, and healthcare-associated pneumonia reducing ventilator-associated pneumonia in intensive care: impact of implementing a care bundle chiche@aphp.fr annals of intensive care national nosocomial infections surveillance system. national nosocomial infections surveillance (nnis) system report, data summary from critères d'infection chez les brulés unité d'épidémiologie et recherche clinique international study of the prevalence and outcomes of infection in intensive care units risk and prognostic factors of ventilator-associated pneumonia in trauma patients ventilator-associated pneumonia: never enough, never give up! sahar habacha , bassem chatbri , aymen m'rad , youssef blel , nozha brahmi sahar habacha -sahar.habacha@gmail.com annals of intensive care weaning patients from the ventilator automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children: a cochrane systematic review and meta-analysis unité de réanimation et de surveillance continue, service de pneumologie et réanimation médicale noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial risk factors for extubation failure in patients following a successful spontaneous breathing trial s a multicenter prospective observational study of extubation procedures in intensive care units: the free-rea study audrey de jong -audreydejong@hotmail.fr annals of intensive care early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the macocha score in a multicenter cohort study faouzi saliba -faouzi.saliba@pbr.aphp.fr annals of intensive care réanimation médicale polyvalente, hôpital de la source mickael landais -mickaelandais@gmail.com annals of intensive care perioperative fasting in adults and children: guidelines from the european society of anaesthesiology the decision to extubate in the intensive care unit service de réanimation médicale s refeeding hypophosphoremia in a medical critical care unit: -month observational study gioia gastaldi -gioia.gastaldi@chu-rouen.fr annals of intensive care refeeding hypophosphatemia in critically ill patients in an intensive care unit. a prospective study refeeding syndrome: problems with definition and management biosit and inserm u , faculte de medecine, université rennes immune dysfunction after cardiac surgery with cardiopulmonary bypass: beneficial effects of maintaining mechanical ventilation s influence of neutropenia on mortality of critically ill cancer patients: results of a systematic review on individual data quentin georges brazil; department of critical care medicine and division of pulmonary and critical care medicine united kingdom; department of intensive care centre d'infection et d'immunité de lille equipe -basic and clinical immunity of parasitic di delta nlr") were calculated. statistical analysis used appropriate non parametric tests and cox regression for survival analysis. the ability of the variables to discriminate survivors from non-survivors was determined using roc curves results during the study period, cirrhotic patients were admitted in icu. the etiologies of liver cirrhosis were alcoholic in % of cases with severe score: median child-pugh score = %) deaths after icu discharge during the same hospitalization. nlr decreased for survivors between d and d univariate analysis, for predicting survival, higher values of nlrd , delta nlr, meld score at admission, sofa score at admission and at day and delta sofad -d were significant factors. predictors of death in multivariate analysis are shown in fig. . area under delta nlr roc conclusion the blood nlr is a novel inflammation index that has been shown to independently predict poor clinical outcomes. we have demonstrated that delta nlr is an independent predictor of mortality in critically ill cirrhotic patients the association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study gene-and exon-expression profiling reveals an extensive lps-induced response in immune cells in patients with cirrhosis celine dupre -duprecece@gmail.com annals of intensive care diagnostic accuracy of procalcitonin in critically ill immunocompromised patients the role of pattern-recognition receptors in innate immunity: update on toll-like receptors esm- is a novel human endothelial cell specific molecule expressed in lung and regulated by cytokines thoracic ultrasound: potential new tool for physiotherapists in respiratory management. a narrative review the care guidelines: consensus-based clinical case reporting guideline development department of physical medicine and rehabilitation icu-acquired weakness and recovery from critical illness o where should we place the stethoscope's chestpiece to hear the noise of the primary bronchi? frédéric duprez , bastien dupuis , grégory cuvelier , thierry bonus frédéric duprez -dtamedical@hotmail.com annals of intensive care o aerosol delivery using two nebulizers through high flow nasal cannula: a randomized cross-over spect-ct study correspondence: jonathan dugernier -jonathan.dugernier@uclouvain.be annals of intensive care introduction in , an international consensus conference took stock of the various measures to be implemented for the prevention of ventilator acquired pneumonia (vap) [ ]. these measures are often gathered in groups of or under the term of "ventilator-bundle. " the effectiveness of these "bundles" was poorly evaluated in african environment. objective to establish a vap prevention program and assess its impact on morbidity and mortality of patients under mechanical ventilation in our service. patients and methods prospective, mono centric, quasi-experimental before-after study. it took place in the intensive care unit of the university clinics of kinshasa in the democratic republic of congo (drc). this service is equipped with beds and a respirator for two beds. the observational period (phase ) was carried out from february st to december st, and the intervention period (phase ) from february st, to february st, . all consecutive patients intubated and mechanically ventilated for more than h were included. five preventive measures were held: hand hygiene, the elevation of the head of the bed at °- °, the daily lifting of sedation, oral decontamination with chlorhexidine and control cuff pressure of the endotracheal tube. compliance with this bundle was assessed by direct observation without the knowledge of caregivers. the diagnosis of "vap" was held before a clinically modified sore (m cpis) > . the main outcomes were the incidence of vap and mortality. the protocol for this study was approved by the ethics committee of the school of public health of the university of kinshasa, under the approval number: esp/ec/ / .introduction nosocomial infections (ni) are common in burn patients due to the loss of the first line of defense against microbial invasion, immunocompromising effects of burn injury, and invasive diagnostic and therapeutic procedures. the objective of this study was to identify the incidence of nosocomial infection (ni), the pathogens and their antibacterial patterns, and prognosis of these burn patients. patients and methods a retrospective study was conducted in a bed intensive burn care unit during months. patients were eligible for the study, if they met the following criteria: total burn surface area (tbsa) > %, length of icu stay ≥ h, and infected in accordance with the criteria of the national nosocomial infections surveillance (nnis) and the criteria of the sfetb [ ][ ]. in this study, nis were classified into four main groups: pneumonias, bloodstream infections (bsi), catheter related infections (cri), and urinary tract infections (uti). for included patients, skin levy, blood cultures, urine and sputum cultures were drawn during fever or clinical features of sepsis. results during the -month study period, patients were admitted to the icu, patients were included ( . %). were male and female. the mean age was ± yr. the mean tbsa was ± %. % were admitted from another hospital. burn injuries were due to domestic accidents in % and self immolation in %. the mean none. none. none. none. none. none. none. none. none. none. ann. intensive care , (suppl ): none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. consulting activities with fisher & paykel. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. failure extubation in intensive care unit: risk factors, incidence and evaluation of a mechanical ventilator weaning protocol lucie petitdemange , anne sophie guilbert none. none. none. none. none. none. opportunistic infections in patients with solid tumors: a systematic review julien poujade , elie azoulay none. invasive aspergillosis in non-immunocompromised patients hospitalized intensive care unit guillaume trumpff , max guillot , thierry braun , ralf janssen-langenstein , marie-line harlay , jean-etienne herbrecht introduction characteristics and outcomes of adult patients with invasive aspergillosis in intensive care unit have rarely been described. we performed a retrospective study on consecutive adult patients with invasive aspergillosis who were admitted form january through january to the intensive none. noorah zaid , nawel ait-ammar , christine bonnal , jean-claude merle , francoise botterel , eric levesque anesthesia and intensive care medicine, chu henri mondor, créteil, france; unité de parasitologie-mycologie, département de virologie, bactériologie-hygiène, parasitologie, hopital henri mondor, créteil, france correspondence: eric levesque -eric.levesque@aphp.fr annals of intensive care , (suppl ):s introduction liver transplant recipients have high rate of invasive fungal disease (ifd) with high morbidity and mortality, in part due to its delayed diagnosis. the fungal cell wall component ( , )-betad-glucan (bg) is a biomarker for fungal infection but its utility remains uncertain. this prospective study was designed to review our experience in ifd and to evaluate the impact of bg in the diagnosis of ifd. patients and methods from january to may , liver transplantation were performed in our institution. serum samples were tested for bg (fungitell; cape cod inc., usa) least weekly between liver transplantation and their discharge from hospital. ifd was defined as proposed by the european organization for research and treatment of cancer/mycoses study group. results nineteen patients ( %) were diagnosed with ifd including cases of candidiasis infection (ci) in eleven out of patients, invasive pulmonary aspergillosis (including one who had previously ci) and one case of septic arthritis of the hip caused by scedosporium spp. ifd was associated with significantly high mortality (log-rank p = . ). the area under the roc curves, for bg to predict ifd, was . ( % ci . - . ). using a cutoff of pg/ml, the most discriminative cut-off point from the roc curve, the sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) values of bg for overall ifd was % ( % ci, - ), % ( % ci, - ), % ( % ci, - ) and % ( % ci, - ). conclusion based on its high npv, bg value appears to be a good biomarker to rule out the diagnosis of ifd when the value is below pg/ml. a single point bg may guide the investigation and the decision to start antifungal therapy in patients at risk for ifd. none. monitoring of changes in lung and chest wall mechanics in the supine, lateral and prone positions during the prone positioning maneuver in ards patients zakaria riad , mehdi mezidi , hodane yonis , mylène aublanc, , sophie perinel-ragey, , floriane lissonde , aurore louf-durier, , romain tapponnier , jean-christophe richard , bruno louis, , claude guérin , plug working group réanimation médicale, hôpital de la croix-rousse, lyon, france; inserm, u , equipe , équipe biomécanique cellulaire et respiratoire, université paris-est créteil -faculté de médecine, créteil, france correspondence: zakaria riad -zakaria.riad@icloud.com annals of intensive care , (suppl ):s none. introduction systemic rheumatic diseases (srd) are autoimmune diseases that are rare but cause substantial morbidity and mortality. srds chiefly affect the lungs, however, data on critically ill patients with srd admitted for arf are scarce. patients and methods retrospective cohort conducted in french icus ( . the major comorbidities were cardiovascular ( %), tobacco exposure ( %), chronic kidney disease ( %) and neoplasia ( %). two-thirds of patients were on systemic corticosteroids at admission, the median dose of (iqr) mg per day. srd diagnosis was made in the icu in . % of patients. clinically or microbiologically documented bacterial pneumonia was the leading arf etiology ( . %). in % of cases, arf was related to an opportunistic infection (mainly aspergillus (n = ) and pneumocystis (n = )). others arf etiologies included specific lung involvement ( . %) and cardiac pulmonary edema ( . %). sofa on day one was [ ] [ ] [ ] [ ] [ ] [ ] [ ] . associated organ dysfunctions were mainly hemodynamic ( %) and renal ( %). mechanical ventilation was needed in % of patients (non invasive only in . % or invasive in . %), % needed vasopressors, and % renal replacement therapy. systemic corticosteroids were started in % of patients and % of patients received pulse steroids. cyclophosphamide and plasma exchange were required in and % of patients, respectively. length of icu stay was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days. icu-acquired infection occurs in % of cases. in total, patients ( . %) died throughout the icu stay. arf etiology was not associated with mortality. by multivariate analysis, shock on admission (or . [ . - . ], p < . ) and the use of invasive mechanical ventilation (or . [ . - . ], p = . ) were independently associated with mortality, whereas non-invasive ventilation was associated with decreased mortality (or . [ . - . ], p = . ). by considering among the connective tissue diseases, the groups of myositis and scleroderma (n = ), these diseases were associated with a trend for a higher mortality (or . [ . - . ], p = . ). conclusion in patients with srd, arf is associated with a high case fatality, primarily when mechanical ventilation is needed. particular attention must be given to specific srd-sub groups for which pulmonary flare may require intensive immunosuppression. none. none. none. severe acute pancreatitis in icu: management and outcomes of infected pancreatic necrosis charlotte garret , matthieu peron , emmanuel coron , cédric bretonnière , jean reignier , christophe guitton réanimation médicale, chu hôtel-dieu nantes, nantes, france; the acute pancreatitis appears as a pathology that we can define with difficulty because of its clinical presentation or prognosis. patients and methods in our study, we analysed cases of acute necrotic and hemorrhagic acute pancreatitis, hospitalized at the department of resuscitation of the surgical emergencies (p ) of the uhc ibn rochd casablanca during the period ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the purpose of this study is to do a descriptive analysis of the epidemiologic, clinic, radiological, therapeutic and evolutive data of the acute necrotic pancreatitits, we included in our study patients with epidemiologic, clinic, radiologic, biologic criteria of acute necrotic pancreatitits diagnosis whatever is the biliary or alcoholic etiology. the valuation gravity of the pancreatitis has been based on:• ranson bioclinical score > /apache ii > ; • visceral failure.• spreading of the necrosis. the analysis of the results shows that: about the epidemiologic aspect: mean age ( year old), the biliary etiology predominates ( %). about the clinical aspect: pain ( %) vomiting ( %), stop of the transit ( %), the visceral distresses are: the shock ( %), respiratory distress ( %), and neurological distress ( %). about the radiological aspect: pleural effusion ( %), abdominal echography: vesicular lithiasis ( %), dilated principal biliary duct ( %), abdominal computerized tomography: stage e ( %). about the biological aspect: hyperglycemia ( %), hyper-amylasemia ( %). the indexes of gravity that have been appreciated in this study are: ranson score > ( %), imrie score > ( %), igs score ≥ ( %), osf score ≥ ( %). the treatment of the anhp has been symptomatic in particular and the evolution has been characterized by mortality about %, the cause was particularly infectious. the prognostic factors predetermined in this study are:• female type (p = . ).• hemodynamic distress (p = . ).• respiratory distress (p = . ).• scores of gravity:• ranson > (p = . ).• imrie > (p = . ).• osf ≥ (p = ).• infection (p = . ).• duration of the hospitalization (p = . ).• rate of c-reagent protein (p = . ). in conclusion, the mortality is still high in the anhp, considerable effort of search is necessary to prevent the infectious complications of mortality. none. predicting -day mortality following liver transplantation in patients with acute-on-chronic liver failure: a decision-tree model from the french national liver transplantation system, the optimatch study, - none. none. none. none. none. none. the french law and recent expert opinions have emphasized the need for a multidisciplinary approach in decisions to forgo life sustaining therapies for the critically ill. we sought to assess how icu nurses actually rank their involvement and perceive this process. materials and methods we conducted a cross sectional survey using a web-based questionnaire between june and september . results of the icus invited to participate, ( %) agreed. a total of icu participants completed the survey of whom % were nurses and % assistant nurses. median age was (inter quartile range - ) years and % were female. median work experience was ( - ) years and time in the icu was ( - ) years. eighty-five percent of the participants have been involved at least once in a multidisciplinary end-of-life discussion. less than half of the participants reported a good ( %) or partial ( %) knowledge of the current end-of-life legal framework. the decision to start a discussion about withdraw life-sustaining therapy (wlst) was initiated by a senior intensivist in % of the cases, by a nurse in % and an assistant nurse in . %. this decision was approved by % of the participants. the decision-making process was considered to be initiated at the right time for % of the participants, too late for %, and too early for %. the discussion occurred mostly in the afternoon ( %) or during the medical staff ( %), in a dedicated place in % of the cases. a median of ( - ) health-care professionals attended the wlst discussion. half the respondents reported being reluctant to talk during the discussions and % never expressed their own opinion. indeed, although the length of the discussion was ( - ) minutes, participants estimated to talk during only ( - ) minutes. the following reasons were mentioned by the participants to explain these facts: having cared for the patient for too short time ( %), lack of medical knowledge ( %), decision of wlst already taken by the medical staff ( %), their opinion not really taken into account ( %), reluctant to talk during meetings in general ( %), consider that the discussion is limited to a medical expertise ( %), limited professional experience ( %), and fear to express a different opinion ( %). nevertheless, % of the participants were partially ( %) or totally ( %) satisfied by the way the decision making process was conducted, % considered that collegiality was applied, and % agreed with the final decisions.conclusion icu nurses rank favorably multidisciplinary wlst discussions. nevertheless their involvement in the discussion remains limited. beyond factors related to work organization and professional experience, efforts should be made to recognize their role and value, and to encourage them to share their own opinions with the other members of the icu team. none. determinants and prognosis of elevation of high-sensitivity cardiac troponin t in patients hospitalized with vasodilatatory shock marie caujolle , jérôme allyn , dorothée valance , caroline brulliard , none. free plasmatic mitochondrial dna-receptor for advanced glycation end-products: a new signaling pathway of critical illness-induced endothelial dysfunction arthur durand , rémi nevière , florian delguste , eric boulanger, none. quality of reporting of fluid responsiveness evaluation studies: a five year systematic review izaute guillame , matthias jacquet-lagrèze , jean-luc fellahi none. none. none. none. none. introduction microaspiration of gastric and oropharyngeal contaminated secretions occurs frequently in intubated critically-ill patients, and plays a major role in the pathogenesis of ventilator-associated pneumonia (vap). at basic state, patients with chronic obstructive pulmonary disease (copd) have an increased risk of microaspiration (due to gastro-esophageal reflux disease, pharyngo-laryngeal dys-function…), this risk may even be more important under mechanical ventilation. the main purpose of this study is to determine if copd is a risk factor for global abundant microaspiration (gam) in intubated critically-ill patients. we gathered data about two prospective multicentric randomized trials focused on microaspiration in intubated patients. data about copd were retrospectively collected in order to complete previous data. microaspiration of gastric and oropharyngeal secretions was respectively determined by quantitative measurements of pepsin and salivary amylase in all tracheal aspirates during the first h after intubation. gam was defined as the presence at significant level of pepsin (> ng/ml) and/or salivary amylase (> ui/l) in at least % of the tracheal aspirates. in order to find gam independent risk factors, we realized an univariate and multivariate analysis of the variables collected. results out of patients included in the studies, were analyzed among which patients with copd. patients ( %) had gam. neither copd diagnosis, nor spirometric severity nor specific therapeutics were associated with gam. risk factors for gam in univariate analysis were the age, diabetes, low score in glasgow coma scale (gcs), and no recourse to paralytic agents or vasopressors. after none. none. implementation and impact assessment of a "ventilator-bundle" at the university clinics of kinshasa: before and after study josé mavinga , joseph nsiala makunza , m e mafuta , yves yanga , amisi eric , jp ilunga , ma kilembe none. none. amel mokline , achraf laajili , helmi amri , imene rahmani , nidhal mensi , lazheri gharsallah , sofiene tlaili , bahija gasri , rym hammouda , amen allah messadi burn care department, trauma and burn center, tunis, tunisia correspondence: amel mokline -dr.amelmokline@gmail.com annals of intensive care , (suppl ):s none. none. none. introduction mechanical ventilation (mv) weaning is a crucial step in critically ill patients. mv duration is associated with an increased risk of ventilator associated events, even though its specific impact on mortality has never been clearly demonstrated ( ). automated closed loop systems might help the weaning process. a recently published meta-analysis has reported a reduction in mv duration when using an automated weaning mode as compared to non-automated mode ( ) . however, the different automated modes have not been compared to each other. the objective of this network meta-analysis was to compare the performance of the three major automated weaning modes, i.e. the automode°, the smartcare° and the adaptative support ventilation (asv°) for mv weaning in critically ill and postoperative adult patients. we included all randomised control trials that compared automated closed loop weaning applications either to another automated application or standard care, including weaning according to a written weaning protocol or nurse driven protocols. the three modes of automated modes included in the study were asv°, smartcare° and automode°. the primary outcome was the duration of mv weaning, defined as the time between randomization and a successful extubation. we also planned subgroup analyses in the icu and the post-operative populations. the quality of the studies was assessed independently by two blinded investigators, using the evaluation recommended by the cochrane collaboration. a network bayesian meta-analysis using random effect models and based on aggregate data from the included studies was performed using the gemtc package (r project, vienna). this trial was declared in pros-pero in august (crd ). results search of databased identified articles; were screened for eligibility after removal of duplicates. abstract analysis led to the exclusion of articles with a final full text analysis of randomised control trials. ultimately, trials were included in the analysis, representing ventilated patients. nine studies included patients in the post-operative period while six were conducted in icu. the automated mode was asv° (a) in studies, smartcare° (c) in studies and auto-mode° (b) in studies. all studies reported the duration of mv weaning as defined in our protocol. in all studies, the control group was standard care with a weaning process driven either by nurses or physicians. in studies ( %) a written weaning protocol was used in the control group. all icu studies used sedation protocols based on sedation scores, none of them including systematic daily sedation interruption. each one of the automated application was associated with a significant reduction in the duration of mv as compared to the control. when comparing all different modes using the network meta-analysis framework, asv° appeared to be the best automated mode when it pertains to reducing the duration of mechanical ventilation weaning (fig. ) . subgroup analysis showed similar results in the post-operative and the icu populations. conclusion compared to standard weaning practice, the major automated weaning modes significantly reduced the duration of mv weaning in critically ill and post-operative adult patients. asv° was associated with the most significant effect when compared to the two other automated modes (smartcare°, automode°). further physiological respiratory studies would help to understand the underlying mechanisms accounting for the superiority of asv. none. none. introduction in intensive care unit (icu) patients, diaphragm dysfunction is associated with adverse clinical outcomes. ultrasound measurements of diaphragm thickness (tdi), excursion (exdi) and thickening fraction (tfdi) have been proposed as estimators of diaphragm function, but have never been compared to phrenic nerve stimulation. our aim was to describe the relationship between tdi, exdi, tfdi and diaphragm function evaluated using the change in endotracheal pressure after phrenic nerve stimulation (ptr,stim), and to compare their prognostic value. patients and methods ptr,stim and ultrasound variables were measured in mechanically ventilated (mv) patients < h after intubation ("initiation of mv", under assist-control ventilation, acv) and at the time of switch to pressure-support ventilation ("switch to psv"). diaphragm dysfunction was defined as ptr,stim < cmh o. results patients were included. at initiation of mv, ptr,stim was not correlated to tdi (rho = − · , p = · ), exdi (rho = · , p = · ) or tfdi (rho = − · , p = · ). at switch to psv, tfdi and exdi were correlated to ptr,stim, (rho = · , p < . and · , p = · , respectively), but tdi was not (rho = − · , p = · ). at switch to psv, a tfdi < % could reliably identify diaphragm dysfunction (sensitivity and specificity of and %, respectively), but tdi and exdi could not. this value was associated with increased duration of icu stay and mv, and mortality. conclusion under acv, neither tdi, exdi nor tfdi were related to ptr,stim. under psv, tfdi was strongly correlated to diaphragm strength and, when decreased, was associated with poorer outcome. alexandre demoule has signed research contracts with covidien, maquet and philips; he has also received personal fees from covidien and msd. none. none. none. management of enteral feeding during extubation in the intensive care unit: a multi-center retrospective study in french intensive care units mickael landais , noemie hubert , mai-anh nay , johann auchabie , bruno giraudeau , reignier jean , arnaud w thille , stephan ehrmann none. none. nutritional support in patients receiving temporary extracorporeal life support: a retrospective cohort study arthur bailly , laurent brisard , philippe bizouarn , thierry lepoivre , johanna nicolet , jean christophe rigal , jean christian roussel , bertrand rozec réanimation ctcv transplantation thoracique, chu de nantes -hôpital nord laennec, saint-herblain, france; chirurgie ctcv transplantation thoracique, chu de nantes -hôpital nord laennec, saint-herblain, france correspondence: laurent brisard -laurent.brisard@chu-nantes.fr annals of intensive care , (suppl ):s introduction the optimal nutritional intake in patients receiving temporary extracorporeal life support (ecls), including extracorporeal membrane oxygenation (ecmo) venovenous (vv) or venoarterial (va), remains controversial. enteral nutrition (en) is suspect to increase risk of gastrointestinal (gi) intolerance and intestinal ischemia. so, total parenteral nutrition (tpn) is often preferred. the purpose of this study is to describe the nutrition practices for critically ill patients receiving ecls and identify opportunities for improving nutrition therapy in this population. patients and methods retrospective analysis of patients requiring ecmo-va or ecmo-vv between and in the cardiac surgery intensive care unit of the university hospital of nantes. nutritional support was daily monitored with parenteral intake (glucose, lipid and propofol, protein and albumin, parenteral nutrition) and enteral nutrition until ecls weaning. two groups were compared during ecls period: no enteral nutrition delivered (none or tpn) (anec, n = ) and at least once enteral nutrition delivered (nec, n = ) including en alone and supplemental parenteral nutrition (spn). primary outcome was incidence of gi intolerance and risk factors. secondary outcomes were nutritional adequacy (calculated as overall of calories and protein delivered divided by the theoretical amount requirements: kcal/kg/d and . g/kg/d) and clinical outcome. data are reported as median ( th and th percentiles) or number (%), and analyzed with student's t test for continuous variables and χ test for categorical variables. p < . was considered as significant. none.introduction refeeding syndrome (rs) is a potentially lethal condition that remains underdiagnosed. it is characterized by severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished patients undergoing refeeding orally, enterally, or parenterally. clinical criteria have been proposed for determination of its risk and reported in the national institute for clinical excellence (nice) clinical guidelines. hypophosphoremia (hp) is a prominent feature of the rs and seems to be the earliest abnormality. phosphorus is a vital component of nucleic acids, enzyme systems, and various metabolic pathways. objective to determine the incidence of refeeding hypophosphoremia (rh) < . mmol/l, and severe rh < . mmol/l in a medical critical care unit. patients and methods monocentric, retrospective and observational study with patients from french-speaking icu nutritional survey study frans. critically ill adults (more than yo) were enrolled if they were hospitalized for more than days during a -month period and had an artificial nutritional support. refeeding hypophosphoremia is defined by the occurrence of hypophosphoremia after refeeding. we studied the incidence of hr, risk factors, and prognosis. results patients were enrolled between / / and / / . rh appears in . % and severe rh < . mmol/l in . % (fig. ) . there is no correlation between rs risk factors and rh in our study. logistic regression did not permit to identify neither risk factor nor prognostic modification. there is a lack in phosphoremia measuring ( . %), and overfeeding during the first days occurs in . %. discussion we define that an hypophosphoremia appearing after refeeding is a refeeding hypophosphoremia, and we do not consider others etiologies, such as mechanical ventilation, alkalosis, sepsis, alcoholism, malabsorptive states, poor intake, some medication. our cohort is too small to find some possible correlations with risk factors or prognosis. conclusion refeeding hypophosphoremia is common in our population. hypophosphoremia is not an independent predictor of icu or in-hospital mortality in critically ill patients. the knowledge of the sri requires the follow-up of the phosphoremia during nutrition after critical illness in particular in the undernourished patients. none. introduction to determine the possible relationship between days cumulated proteins ( days cpd) and energy deficits ( days ced) observed in ventilated patients and icu length of stay, duration of ventilator support, incidence of infections and days mortality. patients and methods mixed medical or surgical ventilated for at least days adult patients from icus from chu liège belgium were enrolled into the study. they were fed by enteral route with a target of kcal and . g of proteins by corrected kg of bodyweight and by day. if % of the target was not reached on day seven, parenteral nutrition was added with the same target. ced and cpd were calculated for days, taking into account all the sources of nutrition, and was defined as the difference between the amount of energy or protein intake and the target. results from / / till / / , patients were followed. data from patients could be cumulated on the first days. there were males, mean bmi was . ± . ; saps ii score on day was . ± . , sofa score at day was . ± . . they were ventilated for a median of days (iqr - ), median icu length of stay was days (iqr - ). mean sofa max calculated for the first days was . ± . and the day mortality was . %. on day , only % reached the target of kcal/kg and % the target of . g of protein/kg. mean days ced was − . ± . kcal and mean days cpd was − . ± . g. there was a significant negative relationship between both deficits and the sofa max (p = . for ced and p = . for cpd). however, there were no correlations between any of the deficits and icu length of stay, duration of mechanical ventilation, occurrence of infections and days mortality. discussion saps ii level, sofa max level, icu length of stay, all these parameters emphasize the high severity of this cohort of patients. it could indeed been thought that it is in this group of critically ill patients that the impact of nutrition could be easily demonstrated. clear relationships between sofamax on day and the days ced and cpd could be seen. however, both the deficit and the level of organ dysfunctions could be cause or consequence. unlike previous studies, usually performed in less severely ill patients, we did not find any relationship between ced or cpd and patient's outcome. conclusion contrary to some recent studies, we found no relationship between ced and cpe and outcome of patients. future studies are needed. none. cardiopulmonary bypass induces lymphopenia and decreases lymphocyte proliferation ability: il- and pd-l as potential therapeutic targets to reduce postoperative infection fabrice uhel , mathieu lesouhaitier , murielle grégoire , baptiste gaudriot , arnaud gacouin , yves le tulzo , erwan flecher , karin tarte , jean-marc tadié fig. incidence of hypophosphoremia at admission, the first day, and refeeding hypophosphoremia none. the prognostic impact of neutropenia in criticallyill cancer patients remains controversial. hence, several studies in critically ill cancer patients failed to demonstrate the impact of neutropenia on outcome [ ] . this lack of statistical association might however, reflect a lack of statistical power. a previous meta-analysis of aggregated data suggested % ( % ci - %) raw increase in mortality in neutropenic patients. the available data were, however insufficient to allow adjustment with confounders [ ] . the aim of this study was to assess the influence of neutropenia on mortality of critically ill cancer patients using individual data obtained from studies identified by our systematic review. secondary objectives were to assess the influence of neutropenia on mortality of critically ill patients while taking into account underlying malignancy, use of g-csf or changes related to period of admission. patients and methods this systematic review and meta-analysis was performed according to the prisma statements. public-domain databases including pubmed and the cochrane database were searched by using predefined keywords. the research was restricted to articles published in english and studies focusing on critically ill adult patients from may to may . the methods and objectives of this systematic review were reported in the prospero database (crd ). selected manuscripts' authors were then contacted to obtained part of their dataset. mortality was defined as either hospital or day- mortality. this preliminary analysis reports results from the whole dataset before and after adjustment using logistic regression. period of admission and use of g-csf were then assessed and were a pre-planned analysis. results our initial search yielded citations and studies were retained for further analysis. overall, studies were excluded for redundancy with other included studies, as containing only neutropenic patients, and two as containing only palliative patients. finally datasets ( %) containing sufficient data to allow comparison were obtained from authors. overall, patients were included in this study, including patients with neutropenia at icu admission. median age was of years (iqr - ). median sapsii score at icu admission was (iqr - ). respectively and patients had underlying haematological malignancy and solid tumours, and patients underwent allogeneic stem cell transplantation. mechanical ventilation, vasopressors, and renal replacement therapy were required in none. none. ( ) . in icus, cirrhotic patients are widely admitted and revalued after receiving optimal treatments for days. however, little is known about how manage these patients after day according to their prognosis. the blood neutrophil-to-lymphocyte ratio (nlr) as a novel inflammation index biomarker has been reported to be a predictor of clinical outcomes in various malignancies and in unselected critically ill patients ( ) . nlr has also been identified as a predictor of mortality in patients with stable liver cirrhosis. to our knowledge, the ability of nlr to predict outcome in critically ill cirrhotic patients has never been studied. the aim of this study was to evaluate the usefulness of inflammatory marker such as nlr for diagnosis of infection and predicting the outcome in hospitalized critically ill cirrhotic patients. we performed a retrospective monocentric study including consecutively cirrhotic patients hospitalized in a medical icu from to . for each patient, clinical and biological data at admission and day were collected. nlr at admission ("nlrd "), at day ("nlrd ") and the variation of nlr between admission and d none.introduction diagnosis of infection in immunocompromised patients can be difficult. however, diagnosing infection is very important, particularly in critically ill. this study aims to evaluate the benefit of procalcitonin (pct) blood level as a diagnostic marker for bacterial infection in patients with hematological malignancies admitted to the intensive care unit (icu). this retrospective single-center study included all consecutive patients with acute myeloid leukemia or high grade lymphoid malignancy admitted to the icu. patients were sorted into three subgroups, according to clinical and microbiological data: «infectious disease», «no infectious disease» and «unknown». initial serum pct and when available at day and day were recorded. receiver operating characteristic (roc) curve, sensitivity and specificity were calculated. serum pct was considered as decreasing when the decrease was ≥ % at day and/or ≥ % at day . mortality rates in the icu and at day- were also studied. results fifty-four patients were included in the study. at diagnosis, pct levels were significantly different between the "infection disease" group and the "no infection disease" group (p = . ). there was no difference between the "infection disease" group and the "unknown" group (p = . ). for the diagnosis of bacterial infection, best initial serum pct threshold was . ng per milliliter. for that threshold, sensitivity was . % and specificity was . %. pct area under the roc curve was . [ci % = . - ]. youden's j statistic was . . pct levels weren't different between groups according to the presence of neutropenia or in case of inaugural disease. there was a significant difference in pct values between groups according to the sofa score (p = . ), but not the saps score. mortality rate in the icu and at day- were significantly lower for the patients with decreasing pct (p < . and p < . , respectively). when comparing serum pct and crp predictive values, pct was significantly a better marker of bacterial infection (fig. ). discussion we found that serum pct, with a threshold of . ng/ ml, is a reliable marker of bacterial infection disease in patients with aggressive hematological malignancy admitted to the icu. our study confirms the results of a previous study in unselected immunocompromised patients admitted to the icu, showing a % sensitivity, a % specificity and an area under roc curve of . [ . - . ] for a threshold of . ng/ml ( ). the main limitations of our study are its retrospective design and the small number of included patients. conclusion pct is a reliable marker of bacterial infection in patients with hematological malignancies admitted to the icu. pct kinetic seems to be an interesting prognostic marker in this population. none. in this study, we have found that kinetics of secretion and expression of endocan is faster with huvecs stimlated by tlr agonist than tlr agonist. this results could suggest that endocan may be not only a marker of septic shock but could be also a specific marker to recognize the nature of pathogenic microorganisms in septic shock. furthermore, other studies with more tlr agonists could be useful to confirm these results. conclusion studying the effects of diverse tlrs agonists could make the plasmatic dosage of endocan more specific and helpful to recognize the nature of pathogenic microorganisms in septic shock. none. lung ultrasound: help to the diagnostic and the monitoring of response to physiotherapy. a case report of pneumonia aymeric le neindre introduction chronic critical illness (cci) syndrome is a new condition affecting an increasing number of patients, who survived an acute critical illness but have persistent severe organ dysfunction, requiring prolonged specialized care. cci is a iatrogenic process, reflecting the efficacy of modern life support technologies( ), and encompasses multiple organ failure, need for prolonged mechanical ventilation (mv), organ support, and palsy due to polineuromyopathy. the transition from acute to cci is gradual: definitions are based on duration of mv, with cut-offs of , or consecutive days of mv for ≥ h/day. cci patients may come from either medical or surgical icu; their health status fluctuates between improvements and deteriorations implying recurrent transitions between different levels of care ( ) .the risk of death is reported to be as high as %. despite a relatively young age ( years on average), functional status of cci patients discharged is seriously impaired, thus cci patients require long-term rehabilitation. aim: to estimate the frequency of cci syndrome in careggi, a large academic, tertiary care hospital; to describe the clinical course of cci patients through discharge, and their functional status at discharge. patients and methods administrative data on admission, transfer, death and discharge of all cci patients, consecutively admitted in one of the icu beds at careggi hospital from january to december , , were collected. cci was defined with the cut off of ≥ days of icu stay, representing the index event (ie) without contribution of previous or subsequent hospitalization in other hospitals. reasons for admission were grouped into the broad categories of medical causes, surgery, major trauma and cardio-respiratory arrest. patients discharged were evaluated in daily living, cognitive status, and mobility using barthel index. results we identified subjects who developed cci ( males; age . ± . years, mean ± sem); of them came from an external icu, began their cci course within careggi hospital ( from the emergency room, from a regular ward). average duration of the ie was . ± . days. these sample developed accumulative length of icu stay of days, corresponding to a % icu bed occupation over the theoretical total of , . when days of subintensive care and regular ward were separately added, days of highly specialized care and days of total acute hospital stay were reached. surgical patients had longer hospitalizations (p = . ).cci patients confirmed to be highly erratic: a total of transitions across different services were recorded in the patients, with a maximum of in of them. mean age was comparable between the patients who died ( %) and the remaining who were discharged alive ( . ± . vs. . ± . years; p = . ).fourteen subjects continued their icu stay out of hospital. only , whose age was lower ( . ± . years), were discharged home; half of the participants (n = , . %) were admitted to a residential rehabilitation facility. younger subjects scored better in the domains of self care (p = . ) and cognitive status (p = . ) but not in the domain of mobility, including walking ability: patients required maximal assistance in performing activities of daily living and transfers, other required medium/maximal assistance, with no statistical difference between dg group. conclusion cci is a relevant clinical condition that need to be assessed and possibly prevented, as it causes severe morbidity, long-term functional impairment and exceeding healthcare costs. none.conclusion early mobilization during the first week of the sepsis onset was safe and preserved muscle fibre cross sectional area. none. none. study of efficacy on icu acquired weakness of early standing with the assistance of a tilt table in critically ill patients none.introduction patients with high flow nasal cannula may benefit from combined aerosol therapy. clinical efficacy depends on pulmonary deposition which is related to the type of nebulizer. all new nebulizers or delivery methods require rigorous evaluation. the aim of this study was to compare lung deposition between two nebulizers (jet nebulizer vs vibrating-mesh nebulizer) through high flow nasal cannula in healthy subjects. patients and methods aerosol delivery of diethylenetriaminepentaacetic acid labelled with technetium- m ( mtc-dtpa, mci/ ml) to the lungs using a vibrating-mesh nebulizer (aerogen solo ® , aerogen ltd., galway, ireland) and a constant-output jet nebulizer (opti-mist plus nebulizer ® , convatec, bridgewater, nj) through high flow nasal cannula (optiflow ® , fisher & paykel, new zealand) was compared in healthy subjects. flow rate was set at l/min through the heated humidified circuit. pulmonary and extrapulmonary deposition were measured by single photon emission computed tomography combined with a low dose ct-scan (spect-ct) and by planar scintigraphy. results lung deposition was only . ± . and . ± . % of the nominal dose with the vibrating-mesh nebulizer and the jet nebulizer, respectively (p < . ). dose lost in the high flow circuit, humidification chamber and nasal cannula was higher with the vibrating-mesh nebulizer as compared to the jet nebulizer ( . ± . vs . ± . % of the nominal dose, p = . ). expressed as percentage of emitted dose, lung deposition was similar with both nebulizers. conclusion this study demonstrated that aerosol delivery through hfnc is poor in the specific conditions of the study despite the higher efficiency of the vibrating-mesh nebulizer as compared to the jet nebulizer. placing the nebulizer on the hfnc circuit at l/min induces high aerosol loss on the circuit and the oropharynx. key: cord- -l z gc authors: chow, justin; alhussaini, anhar; calvillo-argüelles, oscar; billia, filio; luk, adriana title: cardiovascular collapse in covid- infection: the role of veno-arterial extracorporeal membrane oxygenation (va-ecmo) date: - - journal: cjc open doi: . /j.cjco. . . sha: doc_id: cord_uid: l z gc covid- has been associated with cardiovascular complications including acute cardiac injury, heart failure and cardiogenic shock. the role of veno-arterial extracorporeal membrane oxygenation (va-ecmo) in the event of covid- -associated cardiovascular collapse has not yet been established. we reviewed existing literature surrounding the role of va-ecmo in the treatment of coronavirus-related cardiovascular collapse. covid- is associated with higher incidence of cardiovascular complications compared to previous coronavirus outbreaks (sars-cov, mers-cov). we found only one case report from china where covid- -associated fulminant myocarditis and cardiogenic shock (cs) was successfully rescued using va-ecmo as a bridge to recovery (btr). we identified potential clinical scenarios (cardiac injury, myocardial infarction with and without obstructive coronary artery disease, viral myocarditis, and decompensated heart failure) leading to cs and risk factors for poor/uncertain benefit (age, sepsis, mixed/predominantly vasodilatory shock, prothrombotic state and/or coagulopathy, severe acute respiratory distress syndrome, multi-organ failure or high-risk prognostic scores) specific to using va-ecmo as btr in covid- infection. additional considerations and proposed recommendations specific to the covid- pandemic were formulated with guidance from published data and expert consensus. a small subset of patients with cardiovascular complications from covid- infection may progress to refractory cs. accepting that resource scarcity may be the overwhelming concern for healthcare systems during this pandemic, va-ecmo can be considered in highly selected cases of refractory cs and echocardiographic evidence of biventricular failure. the decision to initiate this therapy should take into consideration availability of resources, perceived benefit as well as risks of transmitting disease. covid- has been associated with cardiovascular complications including acute cardiac injury, heart failure and cardiogenic shock. the role of veno-arterial extracorporeal membrane oxygenation (va-ecmo) in the event of covid- -associated cardiovascular collapse has not yet been established. we reviewed existing literature surrounding the role of va-ecmo in the treatment of coronavirus-related cardiovascular collapse. covid- is associated with higher incidence of cardiovascular complications compared to previous coronavirus outbreaks (sars-cov, mers-cov). we found only one case report from china where covid- -associated fulminant myocarditis and cardiogenic shock (cs) was successfully rescued using va-ecmo as a bridge to recovery (btr). we identified potential clinical scenarios (cardiac injury, myocardial infarction with and without obstructive coronary artery disease, viral myocarditis, and decompensated heart failure) leading to cs and risk factors for poor/uncertain benefit (age, sepsis, mixed/predominantly vasodilatory shock, prothrombotic state and/or coagulopathy, severe acute respiratory distress syndrome, multi-organ failure or high-risk prognostic scores) specific to using va-ecmo as btr in covid- infection. additional considerations and proposed recommendations specific to the covid- pandemic were formulated with guidance from published data and expert consensus. a small subset of patients with cardiovascular complications from covid- infection may progress to refractory cs. accepting that resource scarcity may be the overwhelming concern for healthcare systems during this pandemic, va-ecmo can be considered in highly selected cases of refractory cs and echocardiographic evidence of biventricular failure. the decision to initiate this therapy should take into consideration availability of resources, perceived benefit as well as risks of transmitting disease. a significant proportion of patients with confirmed covid- infection experience cardiovascular complications. va-ecmo can be considered in highly selected cases of refractory cardiogenic shock and echocardiographic evidence of biventricular failure. the decision to initiate this therapy should take into consideration availability of resources, perceived benefit as well as risks of transmitting disease. the authors do not have any relevant conflicts of interest to disclose. as covid- has been associated with a multitude of cardiovascular complications ( ) ( ) ( ) , the role of veno-arterial (va) ecmo in the event of covid- -associated cardiovascular collapse has not yet been established. we sought to review the existing evidence surrounding the role of va-ecmo in the treatment of coronavirus-related cardiovascular collapse, in an effort to provide some guidance to providers in the face of the covid- pandemic. compared to other major coronavirus outbreaks such as severe acute respiratory syndrome (sars-cov) and the middle east respiratory syndrome (mers-cov), covid- has been associated with increased incidence of cardiovascular complications ( ) . in one large cohort study of patients, a significant proportion of patients presented with shock (unspecified; . %), acute cardiac injury ( . %) and arrhythmias ( . %), while of patients received unspecified ecmo support ( ) . various case series have also reported newonset heart failure/cardiomyopathy as a complication in up to one-third of critically ill patients admitted with covid- infection ( , ) . st-segment elevation in covid- -associated myopericarditis has also led to false activations of the cardiac catheterization laboratory ( ) . furthermore, among hospitalized patients, the presence of cardiac injury (defined as cardiac troponin above the th -percentile upper reference limit) has been independently associated with a four-fold increased risk of mortality in patients infected with covid- ( ) , with even poorer prognosis in patients who have underlying cardiovascular disease ( ) . the mechanism(s) by which covid- affects the cardiovascular system remain poorly understood but postulated mechanisms include direct myocardial injury, indirect injury through cytokine release, a prothrombotic state causing microvascular thrombosis, and exacerbation of underlying cardiovascular disease e.g. plaque rupture in susceptible patients ( ) ( ) ( ) . we identified two cases from china where covid- -associated fulminant myocarditis and cs was successfully treated ( , ) . in both cases, the diagnosis of covid- was confirmed by sputum nucleic acid testing. both patients had markedly elevated cardiac biomarkers (troponin i/t, nt pro-bnp) and depressed left ventricular ejection fraction by transthoracic echocardiography and were treated with empiric broad-spectrum antimicrobials, intravenous immunoglobulin and corticosteroids. in one of these patients, mechanical circulatory support in the form of va-ecmo was used as a bridge to recovery (btr) with successful hemodynamic and biochemical improvement ( ) . moreover, myopericarditis with left ventricular dysfunction require inotropic support has been reported in the absence of significant pulmonary manifestations ( ) . the extracorporeal life support organization (elso) recommends consideration of va-ecmo in refractory cs that persists despite adequate fluid resuscitation, inotropes and vasopressor support ( ) . contraindications to va-ecmo include (but are not limited to) advanced age, life-threatening non-compliance and significant medical co-morbidities (e.g. severe emphysema or cirrhosis) ( ) . to our knowledge, there are no reported case series' related to the use of va-ecmo in prior coronavirus outbreaks including sars-cov and mers-cov. accordingly, we anticipate that patient selection for va-ecmo in the setting of covid- infection will be a challenging task. however, identification of potential clinical scenarios leading to cs and circumstances unique to covid- may facilitate decision-making (table ) , ideally by a multidisciplinary cs team that includes representation of cardiac surgery, cardiology, intensive care, anesthesia, as well as advanced heart failure/transplant physicians. unique clinical features of covid- need to be recognized before considering candidacy for va-ecmo cannulation in patients with circulatory collapse ( table ) . age is an independent predictor of mortality among va-ecmo patients ( ) with clinical judgment should be encouraged to identify those who are more likely to have an exit strategy, such as btr ( ) . the use of va-ecmo during cardiac arrest is beyond the scope of this review. reported poor outcomes, however, need to be considered before endeavoring to use this approach. we identified one case where a -year female patient with covid- infection was emergently cannulated for va-ecmo during cardiac arrest and cardiopulmonary resuscitation (e-cpr) but unfortunately this patient died shortly afterward ( ) . based on correspondence from existing societal bodies ( , , ) and lessons from the experience in china ( , ), we have distilled the major considerations and recommendations for va-ecmo specific to covid- in table . as international experts have written extensively on the major infrastructure changes needed to support covid- patients with vv-ecmo during this pandemic ( , ) , we expect that much of this will also apply to patients being considered for va-ecmo in the setting of refractory cs. the ethical circumstances surrounding allocation of scarce resources during a pandemic tend to favor a utilitarian approach to maximize collective benefit. important ethical considerations are outlined in the recently published article by emanuel et al. with additional recommendations to prioritize certain groups when constrained by limited resources: health care workers, sickest first, and youngest first ( ) . elso has published guidance ( ) surrounding use of ecmo during this pandemic that align with these principles -namely, that the highest priority should be given to younger patients, those with minor/no medical co-morbidities and healthcare workers. outside of this, standard ecmo inclusion/exclusion criteria and covid- protective equipment should be used according to local institutional policies, as there are currently no special precautions recommended for contact ( ) . although there is a theoretical risk of microbial aerosolization in the ecmo membrane oxygenator, this has not yet been substantiated by evidence ( ) and we do not recommend any special precautions other than vigilant decontamination and disposal of equipment as governed by local institution and infection control policies. pertaining to the provision of ecmo, this is dependent on local institution and regional policies and providing this level of care should be considered dynamically on a case-by-case basis as the local situation and resource availability changes (critical care beds, healthcare personnel, equipment, etc.). in peripheral centers where ecmo is not readily available, additional considerations including ensuring fair resource allocation, as well as the decision to transfer to a specialized center versus cannulation on-site should be determined by similar principles. at our centre (university health network, toronto) ecmo is considered on a case-bycase basis using an interdisciplinary heart team approach in accordance with the most up-to-date elso and canadian cardiovascular society recommendations. to date, we have not yet had any cases of covid- that have required consideration for vv or va-ecmo. that said, this is an evolving situation that may change as more affected patients are expected to require critical care beds in the coming weeks to months. in our current circumstances worldwide -as maclaren et al. suggest -resources may well be better concentrated to ensure that enough icu beds, ventilators and personal protective equipment are available to deal with the influx of patients encountered within the coming weeks to months. as the authors aptly assert, "ecmo is not a therapy to be rushed to the frontline when all resources are stretched in a pandemic" ( ) . covid- has the potential to cause significant cardiovascular compromise warranting consideration for advanced therapies in a small subset of affected patients. frontline providers of all specialties must stay up-to-date with the ever-evolving literature and be familiar with therapeutic options for covid- infections. vv and va-ecmo remain a resource-intensive form of respiratory and mechanical circulatory support that can be considered in extreme circumstances. in the present time of global uncertainty with limited evidence to guide care, we must be mindful of balancing resource scarcity (which may be the overwhelming concern for many healthcare systems in the course of this pandemic) with perceived likelihood of benefit as well as the risk of transmission to other patients, healthcare providers and patient-care environments. we anticipate that ecmo-card (extracorporeal membrane oxygenation for novel coronavirus acute respiratory disease) -an ongoing multicenter prospective observational study of ecmo use in covid- -will inform practice for both vv and va-ecmo use when it is published ( ) . for now, it seems reasonable to reserve va-ecmo for highly selected cases of covid- in refractory cs with echocardiographic evidence of reduced biventricular function, where there is a perceived reasonable probability of benefit as btr. discussions around provision of therapy should be made on a case-by-case basis as part of an advanced cs team which involves input from cardiac surgery, cardiology, intensivists, as well as advanced heart failure/transplant physicians to guide appropriate use of this potentially lifesaving therapy. disclosures: the authors have no disclosures to report. at present, this includes: case-by-case discussion with interdisciplinary heart team usual patient selection criteria as for non covid- patients standard administration, monitoring (e.g. pocus, hematologic parameters) and management of complications standard adjunctive therapies (e.g. lung protective ventilation, crrt) patients referred for consideration of va-ecmo from peripheral centres should be discussed on a case-by-case basis (including the decision to transfer to a specialized center vs. cannulate on-site). determined by standard institutional protocols: at present, this includes: patients on ecmo should be in negative pressure isolation rooms when possible n masks for aerosol-generating medical procedures only droplet-contact precautions otherwise including during cannulation and/or routine rounding handling of ecmo equipment all ecmo equipment should be used and disposed of according to local institutional and infection control policies with attention to practicing strict decontamination. va-ecmo during e-cpr e-cpr should only be performed at experienced institutions (depending on local policy, perceived risk-to-benefit ratio and availability of resources) as the uncontrolled environment of cardiac arrest can pose significant risk of cross-contamination and transmitting infection. clinical, laboratory and imaging features of covid- : a systematic review and meta-analysis on the front lines of coronavirus: the italian response to covid- critical care utilization for the covid- outbreak in lombardy venoarterial extracorporeal membrane oxygenation in cardiogenic shock extracorporeal membrane oxygenation support in novel coronavirus disease extracorporeal membrane oxygenation for coronavirus disease clinical management of severe acute respiratory infection (sari) when covid- disease is suspected: interim guidance surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study coronaviruses and the cardiovascular system: acute and long-term implications cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease (covid- ) pandemic potential effects of coronaviruses on the cardiovascular system clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china characteristics and outcomes of critically ill patients with covid- in washington state cardiac involvement in a patient with coronavirus disease (covid- ) association of cardiac injury with mortality in hospitalized patients with covid- in wuhan, china cardiovascular implications of fatal outcomes of patients with coronavirus disease (covid- ) coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin first case of covid- infection with fulminant myocarditis complication: case report and insights extracorporeal life support organization (elso) guidelines for adult cardiac failure predicting survival after ecmo for refractory cardiogenic shock: the survival after veno-arterial-ecmo (save)-score elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure urgent communication from the ccs/cscs/cancare society covid- ecmo coordinated response team planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases preparing for the most critically ill patients with covid- fair allocation of scarce medical resources in the time of covid- microbial contamination of heater cooler units used in extracorporeal membrane oxygenation is not aerosolized into the environment: a singlecenter experience extracorporeal membrane oxygenation for novel coronavirus acute respiratory disease (ecmocard) study key: cord- -xhx pzhj authors: nan title: nd world congress on pediatric intensive care rotterdam, the netherlands, – june abstracts of oral presentations, posters and nursing programme date: journal: intensive care med doi: . /bf sha: doc_id: cord_uid: xhx pzhj nan we present the results of a prospective population-based audit of paediatric intensive care activity in two comparable communities with markedly different delivery systems. in the trent region of the uk ( . million people), children receive intensive care largely without the supervision of a paediatric intensivist in a variety of hospitals, few of which have designated paediatric intensive care units (picus). critically ill children otherwise receive intensive care in children's wards, special care baby units (scbus) or adult intensive care units. in the australian state of victoria ( . million people), children receive intensive care almost exclusively in one centre -a picu staffed by full time paediatric intensivists. the two regions are otherwise demographically comparable. in both groups, data were collected on all children admitted to an intensive care unit between / / and / / and children who received intensive care (defined by levels of intervention and nurse dependency) in other sites during the same period. values of each variable at first contact with the icu, and the highest and lowest values over the first hours were recorded. the principal outcome was survival to discharge from the intensive care unit. severity of illness was assessed using pim (paediatric index of mortality) and prism. risk-adjusted mortality was compared using flora's z test and logistic regression. the rate of utilisation of intensive care (> admissions in each region) were similar. there was some variation in case mix between the two groups, but crude mortality rates were similar ( . % in trent and . % in victoria). however severity corrected data and other measures of picu performance were dramatically better in' the centralised delivery system. the substantial excess mortality in the trent region provides strong evidence for the benefits of centralisation of paediatric intensive care services. there are considerable difficulties in evaluating the efficiency and effectiveness oflcare in children presenting with respiratory failure during acute medical illness. optimal outcomes for such episodes include survival and the shortest length of stay (los) in intensive care with negligible risk of readmission. we have tried to determine whether or not the time course of acute severe medical illness with respiratory failure is predictable. study i (n= ): a retrospective study of intubated and mechanically ventilated children (> days, < years) with acute severe medical illness. measures: diagnosis, intensive care los in calender days, and survival. results: the underlying diagnosis fell within one of three broad categories: respiratory disease (n= , mortality . %), central nervous system (cns) disease (n= , mortality . %), and systemic inflammation or multisystem (sims) disease (n= , mortality . %. the los in survivors was: respiratory -median (interquartile range) ( - ) days, cns ( - ) days, £p, £ ( -g) days. :i'~'-+cen diag~,~is-rc!ated-grnnp~ (drgs) were identified ( respiratory, cns, sims disease) and each have been characterised by mortality and los. study ii (n= ): a prospective study of patients supported by the hypothesis that los for the above drgs was predictable (compared with study i data). in certain instances attributable causes for variances in los were identified: e.g. disease severity, timing ofdrug therapy, and associated disease. with daily paediatric risk of morality scoring within each drg, four profiles of instability were identified. discussion: the time course of acute severe medical illness with respiratory failure is predictable and variance may be attributable to specific care or diagnostic factors. we are now developing a means of linking drg-specific clinical care pathways with an integrated computerised decision support and education facility at the bedside. the objective of this open, prospective study was to assess the relation between basic patient characteristics as well as effectiveness of treatment on the one hand and resource utilization in pediatric intensive care on the other. as universal, non-monetary indicators of resource utilization we used the therapeutic intervention score system (tiss) and length-ofstay (los), from which indicators for total resource utilization per admission (tisstot) and average daily resource utilization (tiss-mean = tisstot/los) were obtained. overall admissions, totalling days, were included. mortality was . %; non-survivors accounted for . % of overall resource utilization. in non-survivors, both total resource utilization per admission and average daily resource utilization were higher, whereas los was not different from survivors'. severity of illness, surgical status, the presence of substantial chronic comorbidity, emergency admission and transfer from another hospital constituted the major predictive determinants of tisstot (r:= . ) and tissmean (ra= . ) in multiple regression analysis (p< . ). hence these indicators are appropriate non-monetary measures of resource utilization, a considerable proportion of which are determined by a concise set of basic clinical characteristics. subsequently we analysed the relation between effectiveness of care and resource utilization by assessing severity of illness corrected mortality in low, medium and high resource users, respectively. these categories were delineated by percer/tiles of resource utilization (< p , p -ps , > ps ). despite on average long los and high resource utilization in the high risk group, a relatively low standardized mortality was found, probably warranting prolonged intensive treatment in this patient category. summary: objective:the primary purposes of intensive care are to provide treatments to patients with life-threatening physiological dysfunction or to monitor and observe patients perceived to be at significant risk of dying. this collaborative study was performed to describe our patients and their outcome. in order to improve our results we tried to identit~ high risk groups, patients and methods: picus entered the study, the data included all the admissions with > hs. during a days period between the l°june and the th september . the records included: age, sex, weight, mechanical ventilation (mv), post-operative condition (p.op), malnutrition, diagnosis, length of stay, prism score and outcome. student test, mann-whitney or wileoxon were performed for univariate analysis. fisher exact test or chi square for dicotomic variables. risk group analysis was performed by logistic regression, odds ratio and % confidence interval. results: patients entered the study. mean age was . months (ds hh¢# ) and median months. we found significant statistical differences in calculated ,is observed mortality rate comparing malnourished with euthrofic patients; mechanical ventilated (mv) with non mv patients. no differences in ter ~,h of stay or di~ noses were found. effect of the un sanctions on the morbidity rate araong the iraqi small children ( below years old of age ) in bagdad. abdulsamad a.abood / institute of medical technology, bagdad. meningitis is essentially a childhood disease (i). the risk of infection are increased by powerty and overcrowding ( ). the impah'ed immunity may be an important pathogenic factor underlying the susceptibility to infections in undernourished subjects ( ). in general, malnutrition is a man made disease and it begins quite in the womb and ends in the grave (i). small children, below years of age were admitted to the pediatric hospital in washash with meningitis over cold months in i , in contrast to only child admitted with meningitis over the same period in . all of the children who admitted in were frankly undernourished, % of them were infected with enterobacteriae, because they were exposed to faulty hygiene and lack of asepsis. these facts showed precisely that our small children had suffered at most from the un_ sanctions against iraq, because of food, milk and drug shortage, since years which had resulted a severe undernutrition among them, which impaired their immune status. m wells, of riera-fanego, j lipman. baragwanath intensive care unit, university of the witwatersrand, south africa. background the use of prism or other scoring systems in the icu is of great importance for evaluating the efficacy and efficiency of a particular icu, the prism score was developed and validated in the usa and europe but has recently been shown to be inaccurate in a south american population, a south african population as well as several european studies. part of the poor performance of the prism score is as a result of differences in the case mix between the reference population and other paediatric icus. since scoring systems should generally be used only in populations similar to the reference population from which the prediction model was developed, a modification of the prism score is necessary to improve its discriminatory ability in a wide range of patient groups, aim to improve the predictive power of the prism score in a south african paediatdc icu population. patients & methods we analysed prism, demographic and clinical data collected prospectively from consecutive paediatrie icu admissions. the prediction of actual mortality by prism was evaluated by standard statistical methodology (goodness-of-fit test and receiver operating characteristic (roc) analysis), the components of the prism logistic regression equation (prism score, operative status and age) and the physiological variables making up the prism score in addition new variables analysed (nutritional index, the need for inotropes and institution of mechanical ventilation) were subjected to discriminant analysis to determine their association with outcome. results the goodness-of-fit test showed a significant failure of prism to accurately predict mortality over a wide range of expected mortality (chi [ ] = , p = ). prism underpredicted mortality at lower prism scores, but overpredicted mortality in patients with high prisms. similarly roc annysis indicated apoor predic~jve power (az = . ± . ), with an area under the curve significantly less than that for the prism reference population (p = ), prism showed equally poor discriminatory function at all age groups and diagnosfic categories. '~mth the addition of an index of nutrifional status (proportional weight-far-age), and indicators of early respiratory and cardiovascular failure to the logistic regression formula, and a recalibration of the acute physiological score component, the roc can be improved to . ± . , with a good fit described by the goodness-of-fit test (cn ] = , p = . ). discussion the prism score is not accurate in our patient population has been recalibrated in view of the poor discriminatory function that we have shown. part of the inaccuracy derives from the different demographic characteristics of our icu population and a different pattern of diseases. in addition to assessments of acute physiological aberrations, an assessment of nutritional status and early respiratory and cardiovascular failure significantly improve the discriminatory ability of the prism score, these parameters have been devised with a view to improving the accuracy of prism in our population, while not decreasing its accuracy in icus similar to the reference population. in interviewing parents regarding how physicians have communicated bad news, the response i have received is that it has not infrequently been done without appropriate care, understanding and compassion. personal experience and the lessons learned from parents, chaplains and others who deal extensively with these situations have provided me with an approach that has been supportive, compassionate, and caring. an especially difficult communication situation for the intensivist occurs when the parents have to be informed of the death of their child. for the parent, death is the hardest loss of all -the ultimate unalterable loss. circumstances surrounding the death are an important consideration (e.g., a fatal crash caused by a drunken driver, a prolonged illness, a suicide, aids). each produces a different grief reaction. the physician needs to inform parents of their child's death sympathetically coming right out with the news and leaving details until later. allow pauses and time for the paren~ to express sorrow and grief, the best communication may be thoughtful silence and a tender touch. there is disbelief that this happened. it is necessary to repeat oneself. acknowledgment of the parent's "feeling terrible" and the physician's acknowledgment of how terrible he/she feels that the life of the child could not be saved is an important first step in the parent's dealing with this tragic loss. with prolonged resuscitation, it is helpful to have a member of the icu team talk to the parents while the resuscitative efforts are ongoing so that the parents are not left unsupported at this time. a progress report should be delivered in a caring, lucid, and sensitive.manner, indicating that every effort is being made to save the life of their desperately injured child. after a child has died, it is helpful to the family if the physician maintains some contact with them. this should take the form of follow-up telephone calls at approximately , , and months. this can help to screen for depression in the parents. in giving bad news to the family and making every effort to support them through this tragic time, it is necessary to remind oneself that the intensivist has personal needs for dealing with grief and will also require support to pass through this stage. direct evidence that child mortality is lower in specialist pediatric icus comes from studies. a study in oregon (ccm ; : - ) found that mortality adjusted for severity of illness was % of expected in pediatric units and % of expected in general units (p< . ). a study in holland (ccm ; : - ) found that mortality in high risk patients was % of expected in tertiary pediatric units, and % of expected in nontertiary units (p< . ). a third unpublished study, has found that children in victoria (who almost all receive intensive care in a pediatric icu) have a much lower standardised mortality rate than children in the trent region of the uk (where many children receive intensive care in adult icus). there is indirect evidence that icus looking after many children are likely, on average, to perform better than icus looking after few children: numerous studies in many specialities have found that units looking after many cases of a particular disease have better results than units with few cases. see luft hs, "hospital volume, physician volume, and patient outcomes", happ, ; and farley d, medical care ; : - . compared to general icus, medical and nursing staff in pediatric icus are likely to be better at looking ~fter children, and plcu rmos have greater skills in pediatric intubation, ventilation, iv drip insertion and drug doses. picus are more likely to have appropriate equipment to manage children -especially for uncommon but life-threatening situations. icus in pediatric hospitals are more likely to have physicians and surgeons with pediatric expertise available for consultation at all times. the american academy of pediatrics, the society of critical care medicine, the british paediatric association and the australian nh&mrc have all said that children should receive intensive care in'specialist pediatric units. the weight of authoritative opinion, and direct and indirect evidence is strongly in favour of looking after children in dedicated pediatric icus. neurological deficit showed higher cbf values ( . / . ml/ g/ rain.) than the patients with good outcome (mean cbf . sd + . ; cbf . sd _+ . ml/ g/rain}. discussion: in asphyxia decrease of ph is due to reduced tissue oxygenation and indicates the severity of metabolic derangements. co reactivity in newborns with perinatal asphyxia correlates with the lowest ph and therefore may reflect severity of asphyxia. continuous monitoring of cerebral activity is carried out in our unit on all admissions at risk of cerebral dysfunction, a number of monitors are commercially available and we report our experience with the cfam which provides in addition to amplitude integrated eeg analysis, continuous raw eeg display and frequency distribution. bilateral recordings are commenced as soon as possible and continued while clinically indicated. forty one children ranging in ages from weeks to years were monitored for periods from hours to i days, diagnoses included traumatic brain injury ( ), sepsis/meningitis/encephalitis ( t), status epilepticus ( ) and miscellanous others ( ). results are tabulated below. patients status epilepticus * beta activity * background voltage * < i o/zv or more of above * (*z p < , ) asymmetry developed in children, all of whom died. positive predictors of good outcome included a mean background activity of > zzv, the presence of faster frequencies (usually ) in response to sedative drugs and the absence of seizures. all monitoring is performed by the picu staff and increasing expertise in interpretation has resulted in earlier therapeutic and diagnostic interventions. regional it was previously found that histamine, a vasoactive mediator, accumulated in brain compartments (kov~ics et al neurosci lett : ) , and antihistamines prevented brain edema formation (dux et al. neuroscience : ) in asphyxiated newborn pigs. in the present study we investigated the effect of intracarotid histamine injection on the blood-brain barrier (bbb) permeability, left internal carotid artery of newborn pigs ( - h; , - , g; ketamine anesthesia, mg x kg ) was catheterized through the external branch and different doses of histamine ( , - , xi - , - , x , m, respectively, in groups of animals; n= in each) diluted in . ml isotonic saline was injected into the vessel through rain. bbb permeability was determined for a small (sodium fluorescein, sf, da) and a large (evans blue/albumin, eba, kda) tracer ( %, mlxkg , rain circulation time for both dyes) concomitantly in frontal, parietal and occipital cortex, hippocampus, and periventrieular white matter both on left and right sides h after the challenge. then, intravascular dyes were removed by perfusion and bbb permeability for both tracers was quantified by fluorescence spectrophotometry (wavelengths for excitation and emission were nm and nm for sf; and nm and nm for eba, respectively). histamine injection, in doses higher than . m, significantly (p< . ; kruskal-wallis one way anova on ranks followed by dunn's test) increased bbb permeability for both tracers in each brain region. changes in left hemisphere were more intense (p< . ) than those in right one after the doses of xi - and - m in each region, i m histamine administration induced similar edema in both sides. increased intracarotid histamine levels resulted in a dose-dependent vasogenic brain edema formation. histamine might have a pathogenetic role in neonatal hypoxicischemic cerebral injuries. supported by otka f- and h-u.s,-jfno. , $ in coma caused by traumatic brain jnjury, an indication of the likely outcome is provided by the best motor response to pain in the first .$ hours after the insult. in a study in our picu, the proportion of children who died or had a severe disability was % in who had no response to pain, % in with an extensor response, % in with a flexor response, and % in who localized in response to pain. the long term outcome of traumatic brain injury appears to be worse in children < years old. other risk factors in traumatic brain injury are absent basal cisterns, midline shift or subdural haemorrhage on ct scan (or loss of grey-white differentiation in nontraumatic injury); or an intracranial pressure > mmhg despite hyperventilation, mannitol and barbiturate infusion. apart from brain death, there are two findings implying such a poor prognosis that consideration should be given to stopping treatment: first, after traumatic injury, the absence of any motor response to painful stimulus in the cranial nerve distribution (providing drug effects and a post-ictal state have been excluded); and second, in acute brain injury from trauma, infection, hypoxia, or ischaemia, the b{lateral absence of short-latency somatosensory evoked potentials (providing brain stem haemorrhage, subdural and extradural effusions, and decompressive craniectomy have been excluded). in children over months of age, recovery from prolonged coma or a vegetative state is exceedingly rare when more than months have elapsed after traumatic brain injury, and when more than months have elapsed after nontraumatic injury. overproduction of nitric oxide (no) via an inducible isoform of" no synthasc (inos) produces profound vasodilatation in adult septic shock. high nitrate levels have been reported in hypotensive children with sepsis syndrome ]. cardiovascular collapse is a prominent feature of severe meningocoecai disease (mcd). however, systemic vascular resistance (svr) was slightly higher in a group of non-survivors ~ and the rote of no in ivicd remains unclear. children with a presumptive diagnosis of mcd were enrolled. parental consent was obtained. blood was drawn on admission and hrly thereafter. plasma was separated immediately and stored at - °c. the final concentrations reported represent the product of nitrite and nitrate (nox). nox was measured spectrophotometrically using the greiss reaction. children were studied (median age (range); m ( - )). the diagnosis of mcd was confirmed in children, of whom had a glasgow meningococcal score (gms) of" ~ . in this group with severe mcd there were deaths. peak nox was significantly higher (,. ( - ) vs ( - )nmol/ml, median) and systolic btood pressure was significantly lower in children with severe mcd than mild mcd (p< . . wilcoxon rank test). there was a significant correlation between peak nox and gms (spearman's rank correlation r= . (p= . )) and prism (r= . (p: . )). nox production from adm.ission onwards was also higher in the severe mcd group (p: . , kmskal ~wallis). we have demonstrated that plasma nox levels are elevated in children with mcd, correlate directly with the severit ' of disease and are inversly related to systolic blood presssure. similar to hypotensive septic syndrome, mcd appears to be associated with an up-regulation of the l-arginine-no pathway.. non-survivors with mcd have higher svrs and may be relatively hypovolaemic. in our group of severe mcd there was a significantly lower systolic pressure and increased no formation. excess inos expression at different stages in mcd may contribute to the pathology of the disease. the identification of agents which can boost and/or inhibit no reiease may therefore represent different treatment strategies for mcd. u. merz, th. peschgens, g. kusenbach, m. b hle, h. h rnchen in this controlled, prospective study ventilated premature infants with a birth weight < g were randomized to receive treatment with dexamethasone (dex) either on day of life or on day of life. dex was given over days tapering from . mg/kg/day to . mg/kg/day. the infants treated with dex on day of life could be weaned earlier from the ventilator -in median after days (range - ) versus days (range - ) in the [ate treatment group (p = . ). the need for supplemental oxygen was shorter in the early treatment group -in median days (range - ) versus days (range - ) (p = . , ns). the incidence of chronic lung disease was lower in the early treatment group - of infants ( . %) versus of patients ( . %) (ns). to evaluate the long-term efficacy of early dex treatment we performed a respiratory function test in the age of - months using an infant whole body-plethysmograph. the intrathoracic gas volume (itgv), the airway resistance (r.w) and the airway conductance (gaw) were measured and no significant differences could be detected between the groups. the frequency of adverse effects due to dex therapy was found to be without significant differences between the early and the late treatment group. we conclude that early dex treatment had short-term improvements in pulmonary outcome in our study population, long-term efficacy however, remained unproven. several factors contribute to the development of chronic lung disease (cld) in premature infants including structural immaturity of the lung, mechanical ventilation, and oxidative stress. reactive oxygen species are formed during normal cellular metabolism but they are generated in higher concentrations during inflammation or inhalation of high oxygen concentrations. to study the relationship between increased oxidative stress, antioxidants and the development of cld we examined ventilated premature infants with birth weights below t g. infants developed severe chronic lung disease of prematurity (cld), defined by radiological signs of cld and an increased oxygen requirement at a postconceptional age of weeks, and infants had moderate cld with an increased oxygen requirement on day but not at an age of weeks. ventilator settings (fio , peak inspiratory and mean airway pressure) and the incidence of early-onset-sepsis were significantly higher in the severe cld group than in infants with moderate cld or without cld (n= ) during the first week of life. plasma concentrations of the two antioxidative substances bilirubin and uric acid (ua) were comparable in all groups during the first days of life. however, on day seven bilirubin and ua were significantly decreased in the plasma of infants with severe and moderate cld compared to the non cld group (p<o. ). there was no difference between both cld groups. in serially obtained tracheal aspirate fluids (taf) malondialdehyde (mda) was measured by hplc as an indicator of lipid peroxidation reflecting oxygen injury of the lung. ua was found in higher concentrations in taf than bilirubin. ua has been proven to be a potent antioxidant, capable to react especially with hydroxyl radicals and hydrochlerous acid, which play an important role in the induction of lipid peroxidation. infants with severe cld had significantly higher mdnua ratios in taf from day to compared to the non-cld group (p<o. ). mdnua ratios in taf of infants with moderate cld were significantly higher from day on but still lower than in the severe cld group. in addition, the ratio oxidized / reduced glutathione was significantly increased in taf of infants with cld compared to infants without cld between day and . the data support the hypothesis that an imbalance of oxidative stress and antioxidant defense contributs to the onset of cld at the end of the first week of life. introduction. rocuronium bromide (roe), a neuromuscular blocking agent with an onset time dose to that of succinyleholine l'z, has been studied in american society of anesthesiologists' physical status (asa) i or ii pedlatrie patients under non-critical elective conditions. there is a paucity of studies looking at the pharmacodynamics of roc under emergent conditions, involving pediatric patients who are asa iii or iv, without the use of adjuvant inhaled anesthetics ~. methods. with approval of our committee on clinical investigations (irb), roe . mg/kg was administered to asa iii/iv pediatric intensive care patients (age days to months; m:f= : ) on intravenous sedation. the time to reach % a~d % of b~elinc tetanie stimulus response was recorded using a r.elaxogra'ph/qmt- nerve stimulator/recorder (datex, helsiaki). depth of clinical relaxation at the % level was recorded. results. the time from rapid bolus to % was . + . see with a range of - see; and to % was . + . see, with a range of - see. at the % level, excellent clinical relaxation was seen. conduslon. in critically ill children, use of roe at . mg/kg produces rapid onset of neuromuscular blockade and excellent clinical relaxation, such that roe should be considered for rapid sequence intubation. int anesth clin. ; ( ): - . anesthesiology. ; ( ) computed tomography of the chest (ct) in mechanically ventilated adults can detect intrathoracic pathology not appreciated on chest radiographs (cxr) and influence intensive care management. no such data exists for ventilated children. aims: ) to assess if ct provides additional information over cxr regarding extent and nature of intrathoracic disease in ventilated children. ) to determine whether such information alters clinical management, inclusion criteria : ventilated children with cxr changes inconsistent with their respiratory status underwent ct if either a) pao :fio ratio < and/or mean paw> cm h or b) there was an unexplained increase in ventilatory requirement. methods : high resolution ct was performed in patients and spiral ct in patierits, to ensure minimal transport related morbidity, patients were transferred to the ct scanner by a specialised mobile intensive care team. results: in / patients ct demonstrated greater extent of disease than appreciated on cxr but did not significantly alter clinical management. in / patients ct provided additional information regarding the nature of disease present, in / children this involved a further diagnosis and in / children the exclusion of a suspected pathology. new information led to a positive therapeutic intervention in children, prevented inappropriate manoeuvres in , and had no significant effect on acute management in children. conclusions: initial data suggests that in a selected group of mechanically ventilated children chest ct can add to the sensitivity and specificity of intrathoracic diagnosis provided by the chest radiograph and directly influence acute management. case selection criteria and choice of the most appropriate protocol requires further study. pressure control ventilation (pcv) utilizes a decelerating flow pattern which may improve gas distribution and lead to alveolar recruitment. in contrast, volume control ventilation (vcv) employs a constant flow. in children, the effects of pcv as compared to vcv are unclear. the purpose of this study was to determine how these two modes compare in terms of dynamic compliance (cdyn). peak iaspiratory pressure (pip), and mean airway pressure (paw) at equivalent minute ventilation. methods: sixteen infants and pediatric patients ranging in age from day to years were studied. diagnoses included ards ( ), postoperative cardiac surgery ( ), head trauma ( ), and resfrictive lung disease ( ). patients were randomized to pcv ( ) or vcv ( ). initial measurements of gas exchange (abg's) and respiratory mechanics (ventrak, novametrix medical systems) were obtained after a minute stabilizadon period. respiratory mechanics included pip, peep, paw, delivered tidal volume, and cdyn (avolume/apressure). the patients were then crossed over to the alternate mode of ventilation holding delivered tidal volume, peep, inspiratory time, minute ventilation, and fio constant. data were collected after minutes, in each mode the absence of intrinsic peep was confirmed. to assure that the measurements were not affected by changes in clinical status, the patients were returned to the initial mode of ventilation and measurements repeated (final) . patients were ventilated with a siemens c or sv . reselts: data were analyzed using -way analysis of variance with repeated measures. ~ < . vs. vcv) vcv pcv ~ initial ] final ! cdljn . _+ . . _+ . * . _+ . . _+ . i , pip + . l-_t. * _+ , +- , paw . _+ . . i-_ . * . + . . -!-_ . pao _+ +- _+ _+ discussion: at the same minute ventilation, the decelerating flow pattern of pcv resulted in a % increase in cdyn and an % increase in paw while decreasing pip by %. the lack of a significant change in oxygenation may be a result of the limited time in each ventilator mode as well as the inclusion of patients with both normal and abnormal lungs. there was no significant difference in initial and final measurements indicating patient stability. the beneficial effects of iecre~l~iug cdyn and paw while decreasing pip indicate that pcv may be a preferable mode of ventilation in patients with lung injury. further randomized studies examining the effect of pcv on respiratory outcome measures in pediatrics are indicated. prolonged positive pressure ventilation following repair of cdh is associated with a high prevalence of iatrogenic lung injury, in our unit dudng - late deaths after repair of cdh were due to chronic lung disease. since babies requiring assisted ventilation for more than days following surgery were transferred to a cnep chamber to limit lung injury. cnep of - cm of h was combined with positive pressure ventilation via an endotracheal tube dudng the transition phase. immediate reduction of peak inspiratory and positive end pressures were possible and following extubation respiratory support was maintained by cnep v~th appropriate inspired oxygen. overall outcome: [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] n= deaths before surgery (%) ( ecmo during - / who were ventilated for more than days received cnep and there were no deaths and no chronic lung disease in that group. cnep assisted ventilation may be an important management option for babies who require prolonged respiratory support to avoid the adverse effects of chronic positive pressure ventilation, introduction so far modes of liquid ventilation (lv) have been used in experimental animals and, exceptionally, in humans: . total liquid ventilation (tlv)-functional residual capacity (frc) is filled by perfluorocarbons (pfc), and slow tidal volume (tv) breathing is performed by pfc. . partial liquid ve, ti,la~ion (page) -only frc is filled by pfc. gas tv is delivered by conventional mechanical ventilation (cmv), high frequency jet ventilation (hfjv) or high frequency oscillation (hfo). the aim of our study is to present our limited experience with page in newborns and infants. page was used in two groups of infants: , in infants with brain death before disconnection from cmv, because recipients for organ transplantation were not available. these infants have relatively normal lungs (fio~ less than . ). infants stayed on page for hour, during that period no ventdator manipulations were made. after page, infant were switched to cmv for next hours. . very critically diseased infants with ards (rds) - on ecmo more than days, before cannulation for ecmo, on hfo because of intractable respiratory failure, preoxygenated rm (miteni, italy) was used in the doses up to ml/kg intratrachealy. blood gases and parameters of pulmonary mechanics were followed (dynamic compliance -c dyn, airway resistance -raw, bicore monitor). page was combined with no inhalation ( - p.p.m, in infants). in both groups ad hoc an approvement from e local ethical commission and informed parental consent were obtained. in the first qroud with relatively normal lung parameters of oxygenation drops after pfc instilation intratracheally and stayed depressed for - hours. slight pco retention occured in both cases during page. c dyn increased almost double during page period, raw drops transitorily after pfc instilation but in minutes they were identical like in prepage period, parameters of oxygenation (peo /fio ) after - hours after page improved and were better than in prepage period. after that time infants were disconnected and died. in the second group no improvement of oxygenation was seen in one ecmo baby, in spite ()f transient improvement of c dyn. in the second ecmo baby, oxygenation improved and flow of pump could be decreased by more than %. none of these babies, however, survived, improvement was only transient in spite of repeated dosis of pfc. in these babies serious problems were to maintain the adequate frc by liquid, because of severe air leak, in babies on hfo/hfjv with severe ards/rds the improvement of oxygenation were seen in all the cases immediately after pfc instiletion for the period of - hours. after that period, pfc dose had to be repeated. two babies of this group survived. conclusion. page is going steadily from tabs to clinical practice. it is simple, could be performed anywhere, cheaper than tlv. however, because liquivent -perflubren (aliance pharmaceutical) is not available in europe, rm of (mitenti, italy) is the only solution, which could be currently used here. before the widespread use of page in clinics, liquid network among most nicus and picus must be built up, the criteria for page must be defined and ethinal-legal problems resolved as well. after resolution of these particular problems page can be life saving procedure for very special part of critically ill newborns end infants. catherine caronia, peter silver, laura nimkoff, cad quinn, jack gorvoy, and mayer san. division of pediartic critical care, medici,, schneider children's hospital, new hyde park, ny , imroduetiun: cystic fibrosis (cf) patients awaiting lung transplantation present a therapeutic dilenuna when severe respir, aory decompemalion occurs, endotracheal intubation and mechanical ventilation is known to have no long term benefits and is associated with high morbidity and mortality. noninvasive respiratory support appears to be a beneficial alternative. methods: we instituted bipap (respironics, inc,, murrayville, pa) in end-stage cf patients who were admitted to the pediatric icu with severe respiratory decompeusation. all patients were awaiting tung transplantation. after a control period, bipap was applied via a tight fitting nasal or facial mask, using the spo~aneous breathing mode, expiratory pressures were set at - cm hhzo. inspiratory pressures were started at cm ~i o and increased in cm i-i increments until the patient's respiratory comfort was achieved and substantiated by non-invasive monitoring. patients were instructed to use bipap during night sleep and whenever subjectively required, data are reported as mean _+ s.d. results: all patiems utilized nocturnal bipap for - hours/day during a follow-up period of - months. compared to their pre-bipap status, the patiems' oxygen requirement and respiratory rate both oz~ cundusion: bipap tl~rapy improves the respiratory status of decompeusatir!g end-stage cf paacnts. it is well tolerated for long term use at home, and provides an extended period of respiratory comfort and stability for cf patients awaiting lung transplantation. l. bindl*, g. kiihl**, p. lasch***, appel**, j.m er**** and the "arbeitsgemeinschaft ards im kindesalter" background acute respiratory distress syndrome (ards) is a therapeutic challenge in pediatric intensive care in view of the high mortality, in about german paediatlic hospitals founded a working group aiming on collaborative clinical research in this field. aims and methods the aim of both a prospective and retrospective survey conducted in german pediatric intensive care units in was to accumulate data on the epidemiology, risk factors, natural history and treatment strategies in a large group of pediatric ards patients who were treated in the tt~ee year period from to .all patients had acute bilateral alveolar infiltration of noncardiogenic origin and a po ~io ratio < mmhg. the influence of sex, underlying disease and single organ failure was analyzed using the fischer's exact test, the influence of additional organ failure on mortality was tested with the cochran-mantel-haenszet statistics. results patients were reported giving an incidence of cases per admissions to pediatric icus. median age was month. in % of the cases, ards was associated with a pulmonary, in % with a systemic underlying disease. in % immunocompetence was impaired. mortality was % and not dependent on age, sex and triggering event. the number of associated organ failures, however, strongly influenced mortalib,. mortafity in immuno-compromised patients was t %. the analysis of treatment modalifies employed in the patients revealed a lack of uniform therapeutic strategies. on the other hand, the patients were exposed to interventions not yet supported by controlled trials. conclusions the observation of the lack of uniform treatment strategies led to the elaboration of recommendations on ventilator therapy and patient monitoring within the working group. the data gathered in this survey provide the basis for the design of prospective multicenter studies urgently needed to evaluate innovative treatment modafities in pediatric ards. recurrent apnea and respiratory failnre due to severe lower respiratory tract disorders such as bronchiolitis or pneumonia are the most common reasons for mechanical ventilation during respiratory syncytial virus (rsv) infection. acute respiratory distress syndrome (ards) has been described as a complication of severe rsv infectionj in contrast to the low mortality rates associated with rsv infection (< %), mortality rates in the range of - % have been reported in pediatric patients with ards. however, studies on ards are usually lumped in respect to causation and the disease course of rsv induced ards has not been previously studied. we examined the lung function abnormalities of infants with rsv induced respiratory failure requiring assisted ventilation, measurements included respiratory mechanics, maximal expiratory flow-volume curves and lung volumes, ards was defined clinically using the criteria which were recently proposed by the american-european consensus conference on ards~: acute disease onset, pao /fio~ ratio _< mrn hg, bilateral infiltrates on chest radiograph and absence of clinical evidence of left atrial hypertension. we calculated the murray lung injury scores modified for use in pediatric patients from total respiratory system compliance, radiographic findings, ventilator settings and blood gas results. we identified infants with severe restrictive lung disease that fialfilled the clinical criteria fbr classification as ards. all had lung injury scores above . which is the recommended cut-off for a diagnosis of ards, twenty-seven infants had obstructive disease consistent with a clinical diagnosis of bronchiolitis. the ards patients were significantly younger, had a longer time of assisted ventilation (p < . ) and a greater proportion of infants with preexisting illnesses (p= . , odds ratio = . ) when compared to the patients with obstructive disease. with the exception of one immunodeficient patient, none of these infants died. given the low mortality despite a clinical picture of severe lung injury, there is evidence that rsv induced respiratory failure may represent a relatively benign cause of ards in pediatric patients, bachmann an audit of patients with severe acute bypoxic respiratory failure (ahrf) receiving highfrequency oscillatory ventilation (hfov) in our unit ( n= , mortality %) revealed that sub-groups with severe underlying disease (n= , mortality %)and those with mu~pie organ failure ( > systems failing, n= mortality %) accounted for all the deaths beyond the neonatal period. v~ therefore hypothesized that in a modem paedistric intensive care unit (picu): a) children greater than one month of age with ahrf do not die in the absence of severe, pre-existing disease or multi-organ dysfunction syndrome, b) respiratory parameters alone will predict outcome poorly in ahrf. method prospect~/e sty/of all adm~ns to our tertiary picu. data it, citing the respiratory parameters (oxygena~n index [ol] , aiveolar-artedal oxygen tension gradient , pao /fio ratio) were collected hourly from the bedside charts throughout admission. patients were included in the study if ahrf was present at admission either none or in combination with other organ dysfun~on. ahrf was defined as the acute (< hour) onset of respiratory dysfunctk:~l with a pao /fio ratio.< for six consecutive hours dunng the first hours of admission (with no evidence of left anal hypertension), x-ray review defined a sub-group of patients with acute respiratory distress syndrome (ards) by the presence of bilateral interstitial infiltrates. results to date children (ages - months, weight . - kg) have been admitted in ahrf. of these also had ards. the overall mortality was . % ( / ), and greater in the ards group than the non-ards group ( t , . % vs, , . %, p< o. ) . it was not possible to predict survivors from non-survivors on the basis of the seventy of the respiratory failure alone, the a-ado on the day of admission (best in hours) was not significantly different between survivors and non-survivors: (mean, + sd)( mmhg +_ , vs mmhg _+_ ). kdl non-survivors were immunodeficient (n= ), previously extmrnsly premature infants (< ),(n= ) or suffedng fcom chronic metabolic or gastrointestinal disease (n= ). no previously normal child died. conclusion the severity of respiratory failure does not allow predioljon of outcome in our patients. we believe that this reflects that modem picu is so effective at providing respiratory support that pre-existing pathology alone de~ prognosis. this suggests that an abnormally regulated host response or abnormal persistence of a pathogen may be required to induce lung injury of sufficient severity that the resulting respiratory failure cannot be supported in a modem picu. introduction: postural changes (supine to prone) is a therapeutic intervention that could be useful in children with adult respiratory distress syndrome. objective: to determine the effects of postural changes in the oxygenation of young children with ards. method,s: a prospective stud ," was performed in eleven subjects aged to months (mean= ) with the diagnosis of ardsreceiving vendlatory support. (mean peep and fio of and . respectively). postural changes was performed every - hours, during a period of time ranging from to days. arterial blood gases were determined before and - n~n after the postural change, no modification in the mechattical ventilation other that changes in the fio were performed. the oxygenation was determined by the index pao /fi (p/f). to study the differences between the oxygenation mean, before and after the postural changes the wilcoxon test for paired samples was used, results: changes were performed ( from supine to prone and from prone to supine). a % increased p/f ratio was obtained after the change from supine to prune. although, not all the patients receiving postural changes improved their p/f. six of them (group i) showed an improve in the p/f when changed from supine to prone, returning to their base line when positioned from prone to supine. no improvement on the p/f was observed in the remaining subjects (group ii)after postural changes (table ) . during the maneuver no complications were observed. two patients had a pneumothorax, not related with the postural change. conclusions: postural changes (supine to prone) is an easy way to improve oxygenation in some children with ards. change to prone change to supine introduction: the common noninvasive diagnostic efforts to identify possible obstruction of the intrathorucic airway, are of limited value. invasive procedures such as bronchoscopy and bronchography may also be noncontributory and entail risks. we evaluated the usefulness of d-ct in the diagnosis and management of pediatric patients with suspected intrathoracic airway obstruction (itao). methods: we used a diagnostic algorithm (see diagram) in patients with suspected itao resulting in respiratory distress. three-dimensioual imaging of the tracheobronchial tree was reconstructed, following high speed spiral ct scan, by specific computer software (advantage window computer work station, general electric, milwaukee, wisconsin). non-ionic contrast medium was injected, in some patients, to delineate the intrathoracie large vessels.. results: eight patients were studied. in patients the d-ct revealed intrathoracic airway abnormalities. these patients underwent further invesive studies which confirmed the following diagnoses: patients had bronchomalacia, had bronchial stennsis due to a dilated pulmonary artery mad patients had subglottie stenosis extending to the thoracic cavity. three patients had no significant disruption in the configuration of the tracheobronchial tree and thus did not require invasive diagnostic procedures. conclusion: computer reconstruction of three dimensional images of the tracheobronehial tree is a safe and reliable diagnostic tool for itao. ards and ecmo; preliminary data from a randomized clinical trial. j fackler, c steinhart, d nichols, d bohn, m heulitt, t green, l martin, k newth, m klein, j ware. many suggest ecmo be considered experimental for ards and undertaken only with careful data collection and reporting. a mtflticenter pediatric rct is in progress to determine whether ) ecmo and/or ) permissive hypercapnia, offer significant advantage for the treatment of ards. methods: all patients aged wk to yr (without congenital heart disease) are eligible for study. data collection begins when a patient receives at least % oxygen and a peep of cm h for hours (stage t). if the predicted mortality reaches % within days (stage ), eligible patients are asked for written consent for randomization. patients are excluded from randomization with significant chronic lung disease, immune compromise, cardiac disease; or profound acute central nervous system damage. the prime outcome variable is survival. at the studies onset, pts were estimated to be required so that pts were randomized per arm. results: patients are enrolled from centers. data are complete on . patients never reached stage (i.e. % mortality). patients improved and died. of the latter, had randomization exclusion criteria even if stage was reached. patients reached stage . had exclusions from randomization and all died. eight patients ( survivors were eligible for randomization; consent was obtained in no case. two patients received ecmo. overall survival is % ( / ). in patients without randomization exclusions, survival is % ( / ). morbidity m survivors (discharge -admission popc or pcpc score >_ ) was seen in none of the stage surviviors and % ( / ) of those who reached only stage !. conclusion: the rct requires completion. the records of hospital in-patients at king faisal specialist hospital and research center who received external cardiac massage as part of their cardiopulmonary resuscitation were reviewed. success of resuscitation was analyzed as ( ) short term (restoration of spontaneous circulation), and ( ) long term (discharge from hospital). of such patients, ( . %) survived the initial resuscitation, and ( . %) were discharged. success of outcome was not related to age, location of patient, time of day, or rhythm at arrest, including asystole. longer resuscitation time was associated with less chance of restoration of spontaneous circulation (p< . ), but not associated with hospital discharge rate. results for patients with congenital heart disease were similar to those with other medical or surgical conditions. in this series, . % of ward in-patients survived to discharge, compared to two "*;'~r ~r;~' ,.,.'her,, the r-e~ult~ were c/ "'~d ~, ~,°(. overall, % of patients who survived the initial resuscitation were discharged from hospital. where resuscitation continued for more than minutes, . % of patients had tong term survival. outcome from asystole was no worse than for other cardiac rhythms, we believe that previous reports of poor outcome from asystole in pediatric cardiac arrest should noi influence decisions to stop resuscitation for pediatric in-patients prematurely. successful restoration of spontaneous circulation with long term survival can be achieved after prolonged resuscitation. abdelmoniem~ lindsey jahusou~,mariano fiallos, university of florida, prudential drive, suite jacksonville, florida usa central acidosis is well recognized as a marker of inadequate tissue perfusiou, and ventilation. however, obtaining central venous blcod is difficult and fraught with complications in the child undergoing cardiopuimonary resuscitation. intraosseous blood may be used instead of central venous blood to judge ph and pcoz during short durations of cardiopulmonary resuscitation and during hemorrhagic shock. the purpose of this study is to compare the ph and pcoz status of intraosseous and central venous during prolonged cardiopulmonary resuscitation after fluid and drug infusion. we hypotbesized that there would be no difference in ph and pco values of simultanecusly obtained intraosseous and central venous blood samples. eighteen ( ) introduction: cardiopulmonary arrest (cpa) in children is usually preceded by a deterioration of cardiac or respiratory function due to sepsis, dehydration and hypovolemia. early recognition of clinical and laboratory signs followed by immediate intervention are essential for prevention of cpa. the purpose of the present study was to identify factors which contributed to high rates of mortality from cpa in patients admitted to a paediatric intensive care unit (p cu). methods: a prospective study was done of all non-surgical patients with cpa who were admitted to the picu, hospital baca ortiz, quito ecuador from january to october . clinical and laboratory variables before and after admission to the picu, time from hospital admission to picu admission and the pediatric risk of mortality score (prism) were recorded on a questionnaire designed specifically for this study. results: of the non-surgical patients admitted to the picu, ( %) were admitted after developing cpa on the general pediatric wards. mean age was + . months, with of patients under months of age. initial diagnoses upon picu admission included meningitis (n= ), respiratory failure (n= ), congenital heart disease (n= ), severe neurological impairment (n= ), end stage neoplastic disease (n= ), hypovolaemic shock (n=l), peritonitis (n=l) and sepsis (n=l). mean time from hospital admission to p cu admission was _+ . hours. the mean prism score upon hospital admission was + . (score > = > % mortality). % ( / ) of the patients died. one of the three survivors had severe neurologie injury. prior to picu admission, patients experienced tac~,cardia (n= ), hypotension (n= ), neurological deterioration (n= ), respiratory, distress (n= ), oliguria (n= ), bradycardia (n= ), metabolic acidosis (n= ), hyponatremia (n= ), hypokalemia (n= ), hypocalcemia (n= ) and severe hypoglycemia (n= ). there were serious delays from the time of development of clinical and laboratory abnormalities to the time of admission to picu. conclusion: in the critically ill pediatric patient, rapid recognition of clinical and laboratory signs of deterioration, followed by immediate intervention, are required to prevent end stage shock and cpa. we found serious delays in intervention following development of important premonitory clinical and laboratory abnormalities in patients less than months of age on the general pediatric wards, which iikely contributed to the dismal % mortality rate. hospitals throughout ecuador should institute immediate improvements in ctinical supervision, and provide training in paediatric advanced life support (pals) to decrease excessively high rates of and mortality from cpa. intraosscous access is recommended by the american heart association and american academy of pediatries as a means of rapid access to the vascular system for childhood emergencies. bone marrow and fat embolism is a concern and has been reported post intraosseous infusion in stable animals but has never been studied in animals subjected to cardiopuimonary resuscitation. we undertook this study to investigate the incidence and magnitude of lat and bone marrow embolism with the use of intraosseous infusion during prolonged cardiopuhaonary resuscitation and after fluid and drug infusion. we hypothesized that there will be no difference in the magnitude of fat embolism between cardiopulmonary resuscitation only and other cxperirnental conditions. thirty-one ( ) piglets were anesthetized, mechanically ventilated, and instrumented (carotid artery, pulmonary artery and intraosseous earmulas ). the animals then underwent bypoxic cardiac arrest followed by chest compressions with the mechanical thumper (michigan insmunents) and mechanical ventilation for a minimum of minutes. the animals were divided in groups: a (n= ) which had no intraosseous, ~'oup b (n= ) had intraosscous with no infi~ion, and groups c (n= ), d (n= ), e (n= ) had intraosseous with infusion of adrenaline, normal saline and sodium bicarbonate, at cessation ofcardiopulmonary resuscitation, representative lung samples were collected fi'om upper and lower lobes of each lung, embedded in ocp and firozen immediately. ltmg specimens were stained using oil red-o dye and observed for fat globules and bone marrow elements. the amount of emboli present was rated as a percentage in relationship to iung tissue, by a pathologist blinded to the experimental groups. buffy coat specimens were collected before and at cessation of cardiopuimonary resuscitation, stained with oil red-o dye and observed for fat globules. percentage of fat present were compared using analysis of variance. fat globules were seen in the prebronchial blood vessels and in intravascular areas throughout all lung fields. there was no difference in appearance or distribution of fat globules between groups. quantity varied in the different groups[(a) %, (b) %, (c) % (d) %, (e) %], but were not statistically significant (p = . ). fat globules in the buffy coat were few and inconsistent with lung findings. fat and bone marrow emboli were present in all experimental conditions, the use of the intraosseous cannula does not increase the magnitude of embolization during cardiopuimonary resuscitation. the decision to use the intraosscous route should not be influenced by the risk of embolization. tzareva iv/,, md*, nedialkova r, md**, *dept. of pathophysiol, *~dept. of child surg. and icu, emergency medical institute pirogov, sofia, among children with blunt abdominal trauma, treated in emi pirogov during the last five years, children had serious disturbances of the basic vital functions, connected with the trauma, and most often with massive haemorrhage, for this reason being an object of reanimation and intensive care. in the group of children who survived - , predominated the trauma of only one abdominal organ (mainly the spleen, rarely the kidneys, the intestine) and only children had injuries of more than one abdominal organ. in the same group, in children the abdominal trauma was combined with chest or head trauma or bone fractures. in the group of children who died - , a profound combined trauma was present. the haemodynamic parameters in all children showed a characteristically significant tachycardia along with normal or even high blood pressure, while hypotonia was present in only % of the children on the first trauma day. despite the fact that only . % of the children had direct chest injury as well, the gas exchange was considerably disturbed - ' of the children were hypoxemic during the first, and % during the third trauma day -in % significant -below . kpa ( mmhg). together with the markable decrease in haemoglobin levels, this determines the pronounced disturbance in oxygen transport. during the first trauma day all the children were acldo~c, and a metabolic alkalosis was present during the following days. twelve of the children with severe combined trauma died within several hours, with the symptoms of irreversible haemorrhagic shock, or in the next - days, developing multiple organ failure. in conclusion, the intensive therapy of children with severe abdominal and combined trauma, should take in consideration the special haemodynamical trauma answer in children, and requires dynamic monitoring of the most influenced homeostatic parameters -blood gases, acid-base metabolism, haemostasis. introduction: endocrine emergencies, other than diabetic ketoacidosis, are uncommon causes of pediatric intensive care unit (picu) admissions. we report our experience of children diagnosed of adrenal insuficiency (ai) admitted in the picu, during the last four years. subjects: five eases of ai requiring intensive care unit admissions are presented. four females anna male, with ages ranging from days to years, none of them had a previous systemic or endocrine diseases that could suggest al the initial clinical manifestations were: dehydration ( ), vomits ( ), abdominal pain ( ), seizures ( ), lethargy ( ) and hyperpigmentation in the muco-genitat area in a newborn male and ambigna genitalia in a newborn female. the reason for their admission in the p cu were: shock in two subjects; three because of hyperkalemia and hyponatremia (k/na: . / ; / ; , / meq/l); and two with severe hyponatremia (na: ; meq/l). laboratory findings: severe hyponatremia ( ), increased concentration of urinary sodium and chloride ( ); metabolic acidosis ( ); hyperkalemia ( ); increased levels of urea ( ) and hypoglycemia ( ). in all of them, the electrolytes abnormalities did not normalize with replacement and only normalized after the administration of hydrocortisone. tile ai was due to: autoimmtme disease in two subjects, congenital adrenal hypoplasia, congenital adrenal hyperplasia secondary to alia hydroxylase deficiency and in one no etiology was found, at the present time, comments: aiis an uncommon disease in the pediatric age. anearly diagnosis is crucial, as if the treatment is delayed could lead to patients death. in subjects with arterial hypotension and electrolytes abnormalities refractory to the usual treatment, they should be treated with corticosteroids, if no etiology is found. although, previously samples must be obtained to make the diagnosis, : denotes the number of cases. gerbaka b; hakme c; akatcherian c. toxics are frequently involved in domestic accidents during childhood; among non medical products ingestion, carbohydrate poisoning is a serious injury often made possible by inadequate stocking. over years, children aged years and less were examined in the emergency department of hotel-dieu de france hospital for carbohydrate ingestion. , % are boys; age goes from months to years (moan = , years). kerosene is found in , % of cases; all were admitted (mean = , days). , % were symptomatic on first examination but % of all children presented signs of gastric ( %) or respiratory ( , %) irritation sometime during their history; , % had neurological signs and , % presented some fever. leucocytosis is found in % of cases; , % of the children received antibiotics. chest x ray was abnormal in , % of cases: mainly parahilar infiltrates were found, all children survived; , % with a normal course ( , days of hospital stay) whereas those who presented complications (severe pneumonia, coma) stayed in the hospital for days (mean) with short course of assisted ventilation for two of them; long term follow up was not possible. we fonnd nick's criteria for hospital admission to be of value: -symptomatic children with normal x ray } to hours monitoring -asymptomatie children with x ray abnormality } -symptomatic children with x ray abnormality: hospital admission -asymptomatic children with normal x ray : no admission. these criteria would have helped to avoid admission in children and would have allowed a short t hours stay for more. we found chest x ray to be mandatory in carbohydrate ingestion; other tests were not helpful, aside arterial blood gases measurement in case of respiratory involvement; we now also advocate more restriction in antibiotic use. prevention remains efficient and should be stressed on. severe liver failure [slf] is a rare but severe condition in infants. we report our experience. patients: slf was defined as liver insufficiency with hepatic encephalopathy and a decrease in the level of factor v to below %. between and , infants (mean : mo) were admitted for slf (neonates excluded). main causes were metabolic disorders ( . %) (tyrosinemian= , hemochromatosis n= , reye's syndrome n= , other n= ), virus-induced flf ( . %) and hematologic diseases ( . %). in cases, the causes remained undetermined. results: olt was contraindicated in cases because of multiple organ failure (n= ), or underlying disease. all of them died within days after admission. patients had no indications for olt, all but one are alive. ( of them was transplanted later for tyrosinemia and died lately (virus induced-slf). among the t infants who underwent emergency olt, are alive and died because of primary non function of the graft. conclusion: slf in infants admitted before their first birthday is a severe condition with an overall mortality rate reaching %. inherited metabolic disorders are the first cause of slf at this age. contraindications for olt are frequent because of underlying disease or multiple organ failure. a number of children undergo primary graft failure after liver transplantation. it is unknown if there is any increased morbidity or mortality following retransplantation. this study seeks to explore these issues. methods: a pediatric intensive care/iiver transplant database is in formation. records of all liver transplant patients are reviewed and abstracted. this data is then computerized to allow analysis. this data provides the source for this study. statistical analysis was performed via student's t-test where appropriate. results: of the patients who have thus far received at our center orthotopic liver ransplants, the records of who underwent transplants form the basis for this review. twenty-three patients underwent multiple transplants, required one additional, three required organs, and one patient survived after a fourth organ transplant, there was no significant difference in age at first transplant between those who received multiple organs and those who did not ( vs, months, p=ns). the anesthesia time for the procedure did not significantly increase tbr subsequent transplants ( . vs, , hours), nor did time in the intensive care unit (t . vs. . days), nor did time on the ventilator ( . vs. . days) subsequent transplants did not predispose to having more bleeding in the intensive care unit for usage of packed red blood cells or platalets was not significantly altered ( vs ml and vs ml respectively). patients who required retransplantatior~ did receive mere fresh frozen plasma (ffp)daring their first transplant than in the subsequent ones ( vs ec, p < . ). however ffp use was not significantly different than patients who did not require retransplant. patients who underwent retransplant had a markedly increased mortality ( %) than the overall mortality for liver transplants at our center ( %), conclusion: children who require another liver transplant have a markedly increased mortality. bleeding and prolonged icu stay is not significantly different between the first and subsequent transplants, fulminant hepatic failure and ortothopic liver transplantation.dr.sasb n,j;centeno,m;entin,e;acarenza,m;ciocca, m:gofii,j;bianco,g;weller, g;imventarza,o. unidad de cuidados intensivos.hospital de pediatria "dr.j.p. garrahan" .buenos aires.argentina. introduction:fulminant hepatic failure (fhf) is a clinical syndrome, defined by the development of hepatic encefalopathy within weeks from onset of illness in a previously healthy person.by far,the most comun cause of pediatric fhf in all series, is acute viral hepatitis.we report our experiences with the pediatric fhf and ortothopic liver transplantation (olt) as attemative of treatment. patients: childrens with fhf diagnosis were admitted at the picu from / / to / / .symptomatic treatment was given to all children and all were put on list for olt,) following the king's college criterion (protrombina time,age,atiologies,bilirrubin,and encefalopathy state). results:etiologic causes corresponded to the childrens were: , hav ( %); , noa nob ( %); ,autoinmune ( %).the age was mean: years (range: month- years).seventeen patients were transplanted, chidmn were discarded because:no donors: ;withdrow of the list: ,because sepsis in and bleeding of cns ;and no admission at list: because genetic syndrome ,massive intestinal necrosis, ,mitral valvulopathy and sepsis, . patients ( %) had at least one complication dudng the post operative period.the most frequent was the acute renal insufficiency(ari) and patients requiered continuos hemofiltration.the gtobal mortality rate was %.the mortality of patients without olt was % and the mortality of patients with olt was %, patients dayed because sepsis, ( candidiasis) and the others because mof.the actuarial survival at year is % and the follow up of months. conclusions:the fhf is a very severe and frequent disease at picu. supportive treatment only is associated with a very poor prognosis and high mortality rate.the most frequent etiology in our country is the hav. the olt is applicable in this cases and is a valid alternative of treatment (mortality in our series %).the ari is the most frequent complication during the post opeative period.in argentina,due the high prevalence of hav,prevention must be considered the main and only way to avoid this catastrophic illness.- to assess the efficacy of gastric intramucosal ph (phi) for evaluation of tissular perfusion and prediction of hemodynamic complications m critically ill children. patients and methods: thirty critically ill children ( boys and girls) whose age ranged from month and years old were studied. a tonometry catheter was placed in the stomach of all patients at their °admission in pediatric icu. intramucosal ph measures were made at the admission and each - hours during the study: a total of determinations were made. the catheter was removed after extubation and/or checking of hemodyrmmic stability of the patient. the intramucosal ph was derived from application of the henderson-hasselbaeh formula using the pco value from the tonometer and the arterial bicarbonate. values of phi between . and . were considered normal. the relationship between phi and severity of patient measured through prism, presence of major (cardiorespiratory arrest, shock) and minor (hypotension, hypovolemia or arrhytlmtias) hemodynamic complications, mortality and stay in the picu, was analysed. results: the admission value of phi was . -t- . (range . - . ). five patients ( %) had an admission phi < . . no relationship was found between an admission phi < . and a higher incidence of hemodynamic complications. sixteen patients ( %) showed some values of phi < during their evolution. patients with phi < . had a higher number of hemodynanuc complications than the rest (p< . ). every cardiorespiratory arrest (cra) and shock cases were related to a phi < . . patients with major complications (cra and shock) had a phi lower (p= . ), as well as a higher number of measurements of low phi (p= . ) than patients with minor hemodynamie complications. the value of phi lower than presented a % of sensibility and % of specificity with regard to hemodymanic complications. there was no relationship between phi < . and prims score and stay in picu. patients with phi < . presented a prims higher than the rest of patients (p< . ). conclusions: the phi value may be an early sign of presence of hem dyaaimc complications in the critically ill child. we tested the hypothesis that gastric intramural ph (phi) can be used as an early sign of failure m weaning pediatric patients because the blood flow from nonvital areas is diverted to meet the increased demands of respiratory muscles. methods: children (mean age ( . _+ . ) years + sd) who were thought by their physicians to be weanable from mechanical ventilation (mv.). these patients were ventilated on serve c ventilators, receiving ranitidine, and had intestinal tonometer (tonometrics, inc.) minutes before obtaining a sample.. all children were placed on pressure support (ps) at levels judged to overcome the resistance of the endotracheal tube and ventilatory circuit ( em h.,o). a sample of arterial blood and a sample oftonometer were obtained during vm and weaning (ps). phi, hemodynamic and respiratory data were recorded during vm and weaning we did not interfere with the primary caretaker's decisions regarding extubation. patients were considered to be successfully weaned if they were able to sustain spontaneous ventilation for more than hours after extubation. paired t-test were used to compare the values obtained during mechanical ventilation with those obtained during weaning trials. unpaired ttest were used to compare values from the group that was successfully weaned (a=i ) with those from the group that were not (b= ). results: we did not find statistical differences in any of those variables mesured during mv for patients who were successfully weaned(group a) and those who were not (group b). gastric phi was in group a: . + . (vm) and + . (weaning); in group b: . _+ . (vm) and . t _+ . (weaning). discussion: although we did not find differences in gastric phi during vm, the group a had a lower value than group b because of the number of cardiac patients ( %) and transfusion therapy, in fins group. in group b % of patients showed a problem in upper airway (subglottic edema, and enlarged tonsils). we found it after extubation. conclusion: ) gastric phi is a good predictor of risk in critically ill patients but maybe because of the small size of the sample, in our study is not of practical value as a predictor of failure in weaning pediatric patients from vm. ) this test is not a predictor of problems in upper airway~ important etiology of failure weaning in children. objectives: i-to determine the prognostic value of the gastric intramueesal phi in mortality and multiple organ dysfunction (sdmo) in critically ill children. -to compare this value, with the pediatrics risk index mortality score (prims). methods: aprospective study was performed with critically illcbildren, aged from mouth to years. the athnittiug diagnosis was: post-surgery ( neurosurgery, spinal fusion and thoracic or abdominal surgery), sepsis, polytraumatism, adult respiratory distress syndrome and with miscellaneous. all the subjects were monitorized on picu admission and treated for their underlying condition. gastric intramucnsal pt{ was measured following the tonometric method, ou admission and every - hours depending on the patients state. the severity of the clinical condition was evaluated using the the prims, on admission (prims-i) and during the first hours, when the clinical condition deteriorate, the worse score was utilized for the statistical analysis (prims- ). to perform the statistical analysis the subjects were divided in two groups, one with the phi< . and the other with phi> . .aunivariate analysis (student's tand wilcoxon two tailed test, chi-square) and multivariate analysis were used. results: out of the subjects dyed. of children developing multiorgan failure (mof) expired. % of the patients admitted to the picu with sepsis, ards and miscellaneous had a phi < . . in contrast, with % of post-surgical and none of the postqraan~atism. the mortaliry rate, in children with a phi< . was % (ci %: . ; , ) and . % (ci %: , ; . ) in children with phi> . (p= . ). mofwas observed in , % of children withphi< . v.s, . % with phi > . .no relatiouship was observed between the phi and the score of prims-i and . perforating an unconditional logistic regression analysis, two independent variables have mortality predictive value: the phi and the prism- . (table i) following induction of anaesthesia, a laser doppler probe (moorsoft instruments ltd) was inserted cm into the patient's rectum, the probe's special design ensuring that the optical prism lay against the mucosa. continuous monitoring of rectal mucosal perfusion ("flux") was continued throughout the operation. after rain cpb at °c, "steady state" readings of nasopharyngeal temperature, mean femoral arterial pressure (map) and flux were recorded over a further min before cpbinduced core cooling to - °c. steady state was defined as a rain period with no change in core temperatures or map. other rain steady state recordings were taken immediately prior to low flow, immediately prior to rewarming and after rewarming to °c, before initiation of any vasoactive drugs. the cpb flow rate was kept at m l k g - min q, the pcv at _+ %, the p~co at . + . kpa and the pro at + kpa. results: initial warm and rewarm map (both mmhg) were significantly lower ( = . ) than during the cold cpb periods ( & mmhg). the mean cold flux before ( ) and after ( ) low flow were both significantly lower (p= . ) than the mean initial warm cpb flux ( ). the mean rewarm cpb flux ( ) was significantly lower than all other flux values (p= . ). there were no siglaificant correlations between map and flux except at the first warm cpb period (r= , , p= . ). conclusions: although hypothermia significantly reduces rectal mucosal perfusion, rewarming produces an even greater reduction in gut perfusion which, considering that mucosal oxygen constmaption is highest during this time, may prove crucial in the postoperative development of mof. therapy aimed at improving gut perfusion during cpb should be directed at the rewanning period in particular. abstract this work is aimed at establishing a clinical procedure for the diagnosis of enteritis necroticans (en), even at the communal level, and to define criteria for diagnosis able to distinguish between acute forms. subjects and method : cases admitted at the institute for protection of children's health dpch), having characteristic symptoms, were examined clinically, by roentgenography of the abdominal cavity, with the analysis of the blood (total protein, electrolytes, hematocrite) and cultures of intestinal fluid and faeces. through surgical operations, the pathological lesions were observed and recorded. results: common epidemiological features: the average age is - years old ( - ) ; male/female : . ; in % of the cases, the disease occurred after a meal rich in protides. the acute toxic form accounted for % : severe shock appearing early, with very severe dehydration associated with profoundly decreased blood protein concentration and lowered natriemia as well. the lesions of the small intestine were expanded, all of them were necrotic. in the surgical form ( %), the predominant feature was an obstruction -peritonitis syndrome, the peritoneal fluid showed a characteristic inflammatory reaction. for the rest of cases % were the internal form, the shock syndrome was less severe, the abdominal distention was light and disappears gradually, the inflammatory reaction of the peritoneal fluid was not so characteristic. conclusion (ino) is a selective pulmonary vesodilator that is rapidly inactivated compared to intravenous vasodilators. these qualities make ino an attractive agent for the treatment of pulmonary hypertension (pittn). the efficacy of ino has been studied in persistent fetal circulation, acute respiratory distress syndrome (ards), and congenital heart disease (chd). potential adverse effects oflno include: nitrogen dioxide (no toxicity, methemoglobinemia, and platelet dysfimction. our objective was to evaluate the safety of ino in pediatric patients (pts). methods: pediatric pts. with phtn from ards or chd were studied under an established, approved protocol conforming to fda guidelines tbr an investigational new drug. informed consent was obtained for each child prior to treatment. no was sequentially titratad from parts per million (ppm) to , , , and ppm at ten minute intervals. parameters monitored before and during therapy included nitric oxide (no) and no~ concentrations (cone.), mean arterial blood pressure (map), and percent methemoglobin (mhg). no and noz levels were continuously monitored using an inline dr~ger electrochemical detection device. ~,litp was continuously measured with an indwelling arterial catheter. mhg was measured by co-oximetry. a mhg level e % or no cone. ~ ppm were considered adverse effects by study criteria. pretreatment map was compared to map at and ppm ino using paired t-tests. ap value < . was considered statistically significant. results: thirty-two mechanically ventilated children with phtn ( with ards, with chd) were studied. five pts. were treated following cardiopulmonary bypass. methemoglobin (met-hb) levels were routinely measured in two prospective clinical studies on no inhalation in pediatric patients with pulmonary hypertension following heart surgery with extracorporeal circulation and in pediatric and neonatal ards patients, the observed differences between the groups prompted in an in vitro study, red blood cells (rbc) of patients sampled before and after surgery with and without extracorporeal circulation (ecc), respectively, were incubated with ppm no for rain, met-hb, atp, and nadht nadph concentrations were compared, during therapeutic exposure no increased met-hb from . - -_ . to . _+ . % in cardiac surgery patients and from . ± , to . ± . % in ards patients (p < . ). rbc's having undergone ecc were more susceptible to met-hb formation (p< , ) whereas intracellular coenzymes did not differ neither between the groups (table) nor before and after no exposure. ecc predisposes to increased methemoglobinemia upon exposure to no both in vivo and in vitro. our data suggest a reduced activity of met-hb reducing enzymes rather than diminished availability of energetic substrates, variation of the inhaled nitric oxide concentration with the use of a continuous flow ventilator. anne pmc de jaegere ~, frans im jacobs , nico gc laheij , john n van den anker t . dept. of paediatrics ~, central instrumentation , sophia children's hospital, erasmus university rotterdam, rotterdam, the netherlands. objective: to investigate the homogeneity of nitric oxide (no) concentration in a delivery system with a continuous flow ventilator. design: bench study, setting: biomedical laboratory. interventions: a nitrogen/nitric oxide (njno) gas mixture was injected at three different sites in the patient circuit: just before and just behind the humidifier, and centimetres before the y-connector. ventilator flow ( , , l/rain), ventilator rate ( to , increments of ) and compliance of the testlung ( . ; . ; . ml/cm h ) were changed. carbon dioxide (co ) instead of n /no was injected at the same points in the circuit. measurements and main results: a) though the flow ratio of the njno and the ventilator gas were kept constant, the no concentration ([no]) raised with increasing ventilator rates. the increase in [no] was up to % when the n /no injection site was close to the y-connector of the ventilator circuit. minimal changes in [no] were noticed when the n~/no was mixed to the ventilator gas before the humidifier. b) analysis of the ventilator flow pattern showed variations at different places in the ventilator circuit. the magnitude cf the p, ow change depended on the meas~:rement site. the closer to the expiratory valve the highest the flow change was. the duration of the flow change was inversely proportional to the adjusted ventilator flow. c) real time measurements of the co concentration ([coz]) showed variations during tile respiratory cycle. these [co ] variations were higher when the co gas was blended closer to the yconnector. conclusions: the ventilator flow variations in relation to the fixed side flow of the n /no gasmixture result in changes of the inhaled [no] during the respiratory cycle. the no concentration during inspiration is always higher then during expiration. this could not be detected with the available monitoring system. to ensure a constant [no] by blending a njno gas balance in a continuous flow ventilator, the site of injection should be as close as possible to the inspiratory outlet. nitric oxide, a potent and selective pulmonary vasodilator, has recently been successfully used to treat pulmonary hypertension of variable etiology in infants and children. side-effects and complications in infants are so far not well known. we describe here two cases in which prolonged ( and- days respectively) high-dose ( - ppm) nitric oxide was used to treat refractor~¢ pulmonary hypertension. one patient was a newborn infant with pulmonary hypertension secondary to a large leftsided diaphragmatic hernia. nitric oxide was begun under conventional ventilation (babylog ) at hours of life with a slight initial improvement in oxygenation. he was then placed on oscillation with the same nitric oxide concentration due to worsening respiratory failure. he died on th day of life. monitored nitric dioxide concentration never exceeded ppm. the other patient was a months old infant with severe pulmonary hypertension due to a complete atrioventricular septal defect. he required high-dose nitric oxide to come off cardiopulmonary bypass after surgical repair of his heart defect. he slowly improved over the week following surgery but developped suddenly respiratory failure due to massive pulmonary hemorrhage and died. surprisingly, a particular autopsy finding in both infants was a massive acute necrotizing tracheobronchitis. we conclude that nitric oxide is an excellent and sometimes lifesaving treatment of pulmonary hypertension in infants. tracheobronchitis has not yet been reported as a possible complication of nitric oxide administration. we suggest that caution needs to be taken with prolonged high-dose administration and this possible complication to be looked for at autopsy. introduction: permissive hypereapnia (ph) is a beneficial strategy for patients with acute respiratory distress syndrome (ards) to minimize barotrauma by decreasing the peak inspiratory pressure (pip). hypercapnia and hypoxia cause pulmonary vasoconstriction, pulmonary artery (pa) hypertension, and, thus, an increased afterload to the right ventricle. this increased afterload may result in increased right ventricular (rv) work load and subsequent rv dysfunction. one therapeutic approach is the use of inhaled nitric oxide (inn), a selective pa vasodilator. the objectives of this study were to test the hypothesis that in a swine model of ards with ph, inn would improve rv work load and not change intrinsic rv contractility. methods: in swine ( - kg), ards was induced by surfactant depletion. hypercapnia was achieved by decreasing the pip while increasing the peep to maintain a constant mean airway pressure, inn was administered in concentrations of , , and ppm in a random order. pulmonary blood flow (qpa) was determined by an ultrasonic flow probe. rv total power (tp) and stroke work (sw) were calculated by fourier transformation of the pa pressure (ppa) and qpa data. preload recruitable stroke work (prsw), a preload and afterload independent measure of ventriculur contractility, was determined by a shen-subtraction method and vena caval occlusion. respiratory failure with pulmonary hypertension in piglets gerfried zobel*, bernd urlesberger*, drago dacar**, siegfried rtdl*, fritz reiterer* and ingeborg friehs** depamnents of pediatrics* and cardiac surgery**, university of graz,austria objective: to evaluate gas exchange, pulmonary mechanics and bemodynamic data during partial liquid ventilation (plv) combined with inhaled nitric oxide (no) in acute respiratory failure with pulmonary hypertension. design: prospecfive~ randomized, controlled study. setting: university research laboratory. subjects: twelve piglets weighing to kg. interventions: acute respiratory failure with pulmonary hypertension was induced by repented lung lavages and a continuous infusion of the stable endoperoxane analogue of thromboxane. thereafter the animals were randomly assigned either for plv or conventional mechanical ventilation. initially perfhiorocarbon liquid ( ml/kg) was instilled into the endotracheal tube over min followed by - ml/kg~. all animals were treated with different concentrations of no ( - - ppm) inhaled in random order. measurements and results: continuous monitoring included ecg, cvp, mpap, map, san and svo measurements. during plv pao /fio increased significantly from _+ . mmhg to ± mmhg (p< . ) within rain, while pao ]fio remained constant at -+ . mmhg. qs/qt decreased significantly from -+ % to -+ % (p< . ) during plv and did not change during conventional mechanical ventilation. static pulmonary compliance (cstat) increased significantly ff~m . r± . to . _+ . ml/cmh /kg (p< . ) during plv and decreased slightly from . _+ . to . e . ml/cmh /kg during conventional mechanical ventilation. the infusion of the endoperoxane analogue resulted in a sudden decrease of pao /fio from _+ to _+ . mmhg in the plv group and from ± to +_ . mmhg in the control group. inhaled no significandy improved oxygenation in both groups (pao /fio : _+ mmhg during plv and +_. mmhg during conventional mechanical ventilation). during inhalation of no mpap decreased significantly from -+ m ± mmhg (p< . ) in both groups. there was no significant change in oxygenation and mpap during inhalation of and ppm no. conclusions : plv significantly improves oxygenation and pulmonary compliance in acute respiratory failure. the additional application of inhaled no further improves oxygenation and pulmonary hemodynamics when acute respiratory failure is associated with severe pulmonary hypertension. inhaled no is very effective in improving oxygenation and pulmonary blood flow even at low doses. the work was supported in part by grants of the austrian nationalbank nr . as in neonates, severe respiratory failure in infants and children can be aggravated by pulmonary hypertension, resulting in further deterioration of oxygenation due to increasing intrapulmonary shunting. we analysed the influence of inhalational nitric oxide (ino) in treatment, course and outcome of severe ards in a pediatric population. since infants and children (age: - months) with ards and oi > (mean value: . ± ) underwent a trial with ino (concentration: , , , and ppm) to prevent further respiratory failure. patients had a significant improvement of their oxygenation (rise of pa > mm hg) for at least hours (responders); mean best ~fficient no dose: . ppm. the non-responders had only a short-term improvement or ino had no effect. in responders and nonresponders there was no significant difference with regard to age, underlying disease, ards severity, time on mechanical ventilation, blood gases and ventilator settings before notrial, nor was there a different grade of pulmonary hypertension (estimated by echocardiography). the only difference was an higher ol in the group of the non-responders: . ± .i vs. . ~ . , p < . . in the group of the respenders there was a secondary deterioration of lung function after i - days on ino in children (transient responders): in these patients, as well as in the group of the non-responders, alternative modalities of treatment (hfov and/or ecmo) became necessary. children ( %) died: transient respenders and non-responders. in infants and children with ards due to different underlying diseases ino can acutely lead to a significant improvement of oxygenation in about % of the cases. the right selection of patients for no therapy and the influence of ino on the survival rate of ards in childhood has to be evaluated in further studies. and pediatric cardiology, university of graz, a- graz purpose: after fontan procedure cardiac output is critically dependent on the pulmonary vascular resistance. even minor elevations of the pulmonary vascular resistance may significantly decrease cardiac output. inhaled no is an effective, selective pulmonary vasodilator in experimental and clinical situations of pulmonary hypertension. the aim of this study is to evaluate the effects of inhaled no on oxygenation and pulmonm , circulation in children after a bidirectional glenn-anastomosis (n-~) or a fontan-like operation (n= ). material and methods: from june t to january children with a mean age of . +~ . (sem) yrs and a mean body weight of . -+ . (sem) kg were treated with inhaled no after glenn-or fontan-like operations. all but one had complex cardiac malformations with single ventricle. all children were mechanically ventilated with an fin > . . inhaled (no) was applied using a rrdcrdproeessor based system which additionally allowed measurement of no/nox using the chemihimniscence method. methemogtobin concentrations were determined times a day. the major indication for postoperative inhalation of no was a high (> mmhg) transpulmonary pressure gradient (tpg--cvp-lap). severe myocardial dysfunction of the single ventricle was excluded by echocardiography. results: the mean duration of mechanical ventilation was . _+ . (sem) days the. mean dose of inhaled no was . -+ . (sem) ppm, the mean duration of no-inhalation was _+ (sem) hours. the mean methemoglobin concentration was . -+ . (sem)%. hemodynamic data and arterial oxygen saturation before inhaling no and minutes later are given in table acute hypoxaemic respiratory failure (ahrf) in children occurs in a heterogenous group of diseases with pulmonary pathophysiological processes ranging from reversible physiological intrapulmonary shunting to fixed structural lung damage. we hypothesized that inhaled nitric oxide (ino), a selective pulmonary vasodilator, might identify those patients with potentially reversible disease, i,e, large response may indicate a greater likelihood ef reversibility and thus survival. a retrospective review of the early response to ino in infants and children (aged month to years, median months) with severe ahrf( with ards). the mean p(a-a)o , pao / fio , oxygenation index (oi) and acute lung injury (all) score prior to the commencement of ino were +_ . , +_ . , _+ , and . +_ . respectively, the magnitude of response to ino was quantified as the % change in oi occurring within minutes of ppm ino therapy. this response was compared to patient outcome data. results. there was a significant correlation between response to ino and patient outcome, kendall tau b r= , , p< . (table) conclusion. in ahrf response to ino appears te define a subgroup of patients with improved outcome compared to nonresponders. we speculate that response to ino may be useful in selecting patients with potentially reversible lung disease for special support therapies such as ecmo. randomised controlled trials are needed to define the role of ino in paediatric ahrf. between may and december , patients (pts) were treated for mas. treatment groups were: group i only : pts; group i conventional mechanioal ventilation (cmv): pts; group ii hfo: pt; group iv hfo+no: pts. therapy was stepwise intensified until oxygenation improved ( i -) ii -) iii --) iv). "high volume strategy" was used with hfo (mawp - cm h ). the initial no-concentration was - ppm, with rapid reduction down to - ppm once oxygenation improved. results: one pt (group it) died of hypoxic-ischemic encephaiopathy (termination of therapy); all other newborn babies survived. in group iv pt and showed barotrauma prior to hfo. pt , and were treated with additional mgci (max. mg serum concentration . - . mmol/i). following the identification of inhaled nitric oxide "no) as a selective pulmonary vasodilator (frostell et al ) [ .+ , + . data are compared to baseline values within each group. *=p< . , **=p< . , ***=p< . l among patients who fulfilled ecmo criteria, improved with no and did not required extracorporeal life support. tltree out of ecmo patients eventually survived. conclusions: m our study low-dose of irthaled no showed a variable effect on oxygenation in newborns with acute respiratory failure. an acute response to no appeared to be correlated with a better short-term outcome and the avoidance of extracorporeal support in ecmo candidates. differently, lack of acute and/or sustained response was associated with death or need for ecmo. although the nature and severity of the underlying disease or the degree of prematurity may play an important role in these patients, we believe lack of acute response to no may be an early predictor of bad outcome, prompting toward alternative treatments such as ecmo or liquid ventilation. *picea s., °bartuli a.,°dionisi-vici c., *dello strologo l., §villani a., §bianchi r., ^salvatori g.,*rizzoni g, °sabetta g. *div. of nephrology, °div. of metabolism, §intensive care unit, ^div. of neonatology. "bambino gesfl" children research hospital. rome, italy. successful prevention of handicaps or death in newborns with ~ depends on rapidity and efficiency of treatment. poor response to nutritional and/or pharmacological treatment requires extracorporeal removal of nh . efficiency and cardiovascular tolerance are often difficult to obtain with peritoneal or hemodialysis in neonates. we report the results of cavhd in newborns with hc. methods: vascular access: femoral vessels. blood flow: - ml/min, dialysate flow: - ml/h. filter: amicon minifilter plusrm(polysulfone membrane; . sq.m.). no ultrafiltrate(uf) production, patients: case with carbamoytphosphate synthetase deficiency (body weight -bw-: . kg) showed hc at day , a relapse of hc occurred at day due to an infectious event. case and (bw: . and . kg), both affected by propionic aeidemia, showed hc at day and day , respectively. plasma nh (~tg/dl) decrease is shown in the complications: transitory ischemia of arterial cannulation limb and transitory thrombocytopenia occurred in case ; surgical repairing of artery after cavt-id was necessary in case ; no cardiovascular instability was observed during cavhd . outcome,'all patients recovered from hc in less than day: case : alive, mild b)iootonia at mos; case : dead after days from cavhd withdrawal for pulmonary hemorrhage; case : alive, normal development at mos. conclusions: ) in newborns with hc, ca~q-id provides good cardiovascular tolerance,high efficiency and quick removal of nh , even without uf production (i.e. only by diffusion). this allows easier management (no need of fluid and electrolyte balance). ) arterial complications seem frequent in neonates treated by cavhd. venovenous circulation could overcome this problem. vb nguyen, m jokie, c leeaeheux paediatric intensive case service, hospital university centre, avenue c te de nacre, caen cedex, france background, the implication of polymorphonuclear neutrophils (pmns) in the physiopathology of children's haemolytic.uraemie syndrome (hus) becomes more and more evident. the purpose of the present study is to role out their impact among other pronostie elements during the course of the disease. patients and methods. diarrheal prodrome and its duration, patient's age, maximal blood nitrogen level, anuria and dialysis time, extra.renal involvements, white enll and pmn counts and thrombopenia duration have been retrospectively analysed in infants with good outcome and in another children with unfavorable outcome. results. neither diarrhoea or its duration, nor children's age, nor blood nitrogen level, nor anuria or dialysis time had any predictive value for the disease evolution in the acute phase of our patients. adversely, extra-nenal involvements was accompanied by severe and complicated courses of the disease (p< , ). the elevation of white cells and pmns (heyon x /i) and pmns (more than x / ) as well as its persistence beyon a week were most frequently observed in complicated forms (p< , , p< , and p< , , respectively). a transient thrombopenia (less than day@ in patients with elevated counts of white cells may be a filrther obvious sign of an unfavorable course of the disease ( < , ). conclusion. the elevated count of white cells and pmns, either alone or associated to one rapid regeneration of platelets, seems enabled to predict an unfavorable evolution of the hus in children. msud results from an inherited impairement of catabolic pathway of branch chain amino-acids. high leucine blood levels may induce acute brain dysfunction. this dramatic complication led us to propose leucine removal procedures as continuous hemofiltration. patients and methods three newborns in acute msud onset were treated by hf, hdf and hd. extracorporeal circulation was performed through a . fr catheter, a circuit with a blood pump (priming volume = ml). patients and procedures characteristics are summarized below in the sucralfate (an aluminium salt of sucrose octa sulfate) is used to prevent and treat upper gastrointestinal bleeding in critically ill patients. with minimal absorption, the potential for side effects is thought to be limited, though aluminium toxicity has been reported in patients with chronic renal failure. these patients may already have had high body stores of aluminium. we report critically ill children with high serum concentrations of aluminium following sucralfate therapy. all had renal impairment. the normal aluminium level is < . gmol/l and in patients with chronic renal failure < . ].tmol/l. none of these patients had known preexisting chronic renal disease. cpb was conducted under deep hypothermia (t,° °c) and cardiocirculatory arrest (cca) or under hypothermia (t,° °c) and low-flow perfusion. continuous holter-electrocardiograms (h-ecg) were recorded from the ilranediate postoperative (po) period on for hours. h-ecg were also recorded prior to the operation and before discharge. following dr were observed: snpraventricutar (sv) and ventricular (v) extrasystoles (es) (> / h), sv and v tachycardia (svt and vt), accelerated junctional rhythm (ajr) and junctional ectopic tachycardja (jet), and nd and rd degree atrioventricular block (avb and avb ). the incidence of po dr was % in the pre-op h-ecg, % on the st, % on the rid, % on the rd po day and % befbre discharge. compared to the pre-op findings, an increased incidence of sves, ves, svt and avb on the st po day was observed, whereas vt and a jr or jet were exclusively observed po. all types of dr were observed up to the rd po day. ty e of dr before discharge was similar to pre-op findings and there was no definitive avb . considering patient groups according to the most frequent isolated op-procedure, the incidence of dr on the first po day was % after asd ii-closure (n= ), % after stthaortal vsd-closure (n=lg), % after correction of a complete avsd (n= ), % after correction of a tetralogy of fallot (n= ) and % after fontan-operation (n= ). incidence and type of dr were not significantly different between groups. longer cpb-dttration and use of cca were risk factors for po ves and vt (p< , and p< , , respectively) whereas use of cca and degree of hypothermia were risk factors for the development of a jr and jet (p< , and p< , , respectively). -our results indicate that po dr after cpb in children m'e frequent but mainly transient. in our series, specific cpb-related parameters are of greater influence than surgical procedure itseif for the development of dr and are discriminant risk factors for particular types of dr. the course of anp, cgmp/anp (as indicator for atrial natriurefic peptide biological activity), and no and no (as indicator for endogenous nitric oxide (no) synthesis) was investigated in i infants (median age months) undergoing cardiopulmonary bypass (cpb). patients were divided into groups according to whether they had (group , n= ) or not (group , n= ) preoperative heart failure (hf) and pulmonary hypertension (pht). group patients had preoperatively significantly higher levels of anp (p< . ), cgmp (p< . ) and no and no (,p< . ) but had significantly lower cgmp/anp (i < . ) than group patients. during cpb, anp was significantly higher in group patients ~< . ). as compared with prebypass values, cgmp/anp was reduced in both groups during cpb (p< . ). cgmp/anp inversely correlated with duration of cpb and aortic clamping time (p< . , respectively). no and no were significantly higher in group than in group patients (p< . ) without any intraindividual change during cpb. from the early postoperative period on anp, cgmp/anp and no and no were similar in both groups. after cpb, anp correlated in both groups with blood pressure (p< , ) and diuresis (p< . ). no and no inversely correlated with pulmonary arterial pressure immediately after cpb ( < . patients after a fontan-type of procedure have elevated central venous pressures (cvp) leading to congestion in the gastrointestinal system and often ascites. purpose of this study was to evaluate whether this causes a different postoperative gastric mucosal ph (phi). methods: we evaluated a series of patients, who underwent cardiac surgery with cardiopulmonary bypass (age: days to years (mean , yrs), weight: . to kg (mean . kg). a commercially available tonometer (tonometics®) for sigmoidal use in adults was inserted into the stomach after induction of anesthesia. the phi measurements were done according to manufacturer recommendations we compared three groups of patients: ) aeyanotic (n= ), among them p with vsd and p with avsd; ) cyanotic (n= ): tof: p, tga: p; ) cyanotic after a fontan-type procedure (n= ). phi were measured at picu arrival and after h. fudhermore we compared lactat levels at these time points. differences between the groups were evaluated with one way anova on ranks with pairwaise multiple comparisons (dunn's method). the relationship between cvp and phi was investigated by regression analysis. results: the median phi for groups i, and were . , . and . at ardval and . , . and . after h respectively. at picu arrival group was significantly (p< . ) different from groups and . there was no significant difference between the latter two groups, after h group was different from group , there were no other significant differences. the median lactate levels for groups t, and were . , , and . at ardval and . , . and . after h respectively. at ptcu arrival group was significantly (p< . ) different from group , after h there were no significant differences. there was a weak negative correlation between cvp and phi: r= - . ; p< . . conclusion: patients after a fontan-type of procedure have lower phi than patients after other cardiac surgical procedures, however, this is only in part due to the elevated cvp and venous congestion. eleven children were investigated months (median) after postoperative mof. iviof was defined as the failure of at least two vital organ systems (kidney, liver, lung, central nervous system) in addition to cardiac insufficiency and high fever. underlying surgical procedure was repair of tetralogy of fallot (n= ), fontan-(n= ) or seuning procedure (n=l). all patients fulfilled criteria for mof in the first postoperative (po) days. six patients needed peritoneal or hemodialysis for days (median) during the po period. one patient showed cerebral infarction due to thromboembolism in the territory of the right internal carotid artery immediately after the operation. the follow-up protocol consisted of extensive investigations of heart-, renalliver-, and lung functions as well as complete neurological and psychological examinations. all patients had adequate cardiac examination. lung function was normal in all but patients who had an obstructive syndrome. only patient showed an isolated decreased creatinine clearance. abnormalities of the liver ftmction tests were only noticed in patients after fontan procedure. severe neurological sequels such as paraplegia (n = ) and diplegia (n-i) were observed in of the patients. the remaining children presented with a delayed graphomotorical and speech development associated with normal intelligence. -in our series the most frequent and severe sequels after postoperative mof were neurological. -abnormal liver fimction tests are more likely to be a consequence of the fontan hemodynamics than a sequel of mof. the optimal dosing schedule of surfactant therapy for the treatment of neonatal respiratory distress syndrome (rds) remains unclear. goal: surfaetant function and the concentration of phospholipids (pl) in tracheal aspirates are compared in a prospective randomized trial involving neonates with rds who received either two or more ( or ) doses of survanta. methods; ventilated neonates < w with rds were treated with survanta oo mg/kg if fio >_ % or mean airway pressure _> , cm hzo, after h a nd dose was given (same criteria), if the support still exceeded the criteria h after the nd dose, the patient was randomized to no extra dose (two}, or to an extra dose of survanta (morel (and a th dose h later; same criteria), pl was measured in tracheal aspirates and corrected for dilution with the urea method. "active" large aggregates and "non-active" small aggregates of surfactant were separated by centrifugation and quantified. surface tension of the large aggregate fraction was measured by pulsating bubble surfactometer, results: neonates were randomized, x two and x more ( x and x doses), gestational age was , ± , w and birth weight ± g. most patients had severe rds with initial ventilation: rate . _+ , , peak inspiratory pressure (pip) , -+ . cm hzo, fio . ± . %. at randomization: rate . ± . , pip . -+ . cm hzo, fio . ± . %, and h after randomization: rate . ± . , pip . _+ . cm hzo, fio . ± . %, without signif, differences between the groups. there was relapse (again fio _> % within h) in group two and t bpd in group more. in total, tracheal aspirates were analyzed. pl was not signif, different before randomization (two . ± . vs more . ± . /jmol/ml), but neither after randomization (two . -+ . vs more . ± ,o /~mol/ml). there was no difference in the % small aggregates (two . ± . vs more . ± . %), the surface tensions (ran/m) were not signif, different (each time two vs more): before randomization . ± , vs . -+ . , in the h after randomization . ± . vs . -+ , , or - h after randomization . -+ . vs . ± . , or - h after randomization . _+ . vs . -+ . . conclusion: neonates who received more than two doses of survanta did not have higher pl, nor a better surfactant function than neonates who received only two doses of survanta. continuation of the trial is necessary to evaluate clinical outcome. may not indicate need for treatment p.c. clemens s.j. neumann university of hamburg, department of pediatrics, klinikum schwerin, wismarsche str.. , d- schwerin. aim of the study: the finding of elevated tsh and decreased t in the newborn usually is classified as "transient hypothyroidism", thus the elevation of tsh is classified as consequence of the lowered t . but on the other hand several data sets show that tsh elevation as well as low t , one independently of the other one, are associated with different kinds of perinatal stress. each of these laboratory deviations, if not associated with the other value being abnormal too, is generally accepted not to be an indication for treatment. from this we conclude, that more pefinatal stress, as in intensive care neonates, may produce tsh elevation as well as low t , but only coincidentially, not the tsh elevation being the consequence of low t , thus not to be classified as "hypothyroidism", thus not indicating treatment. if this hypothesis is right, we should find an association of increasing pefinatal stress with an increasing number of neonates from tsh and t normal via tsh or t abnormal to high tsh and low t . method: in the newborn screening program in germa w we determine primarily tsh, and only in the neonates with elevated tsh, in addition we determine t . thus in our study we asked whether we find an association of increasing perinatal stress with an increasing number of neonates from tsh normal via tsh abnormal while t normal to high tsh and low t . definitions for this study were: tsh elevation = > mu/ (as usual in the german screening programs), t lowered = < p_g/dl perinatal stress score was or or or in dependency of the neonate having stress in none to all of the following three categories: (a) forceps or vacuum extraction or sectio co) birth weight below g (c) at the th day existence of a relevant neonatal disorder (rds, ictems gravis, infection/sepsis, vitium cordis with hemodynamic relevance, severe malformation). results: our data of neonates show a high significant association (chi = , p < . ) of, on one hand, perinatal stress score with normal tsh, versus, on the other hand, perinatal stress score or with high tsh and low t . discussion: facing the background given above, in the intensive care newborn, the constellation of high tsh and low t may be only a coincidential addition of two independent abnormalities. in tbese cases -the high tsh not being the consequence of low t -the classification as "hypothyroidism" is not justified, thus a therapy not indicated. on the other hand of course there exist rare cases with high tsh as consequence of low t thus with hypothyroidism tlms with indication for therapy. unfortunately we have no criteria, that enable a certain discrimination of these two categories thus in respect to the question of therapy or not. conclusion: further research has to be done to learn how to discriminate the coincidential high tsh and low t from the causal constellation of high tsh and low t . until we have certain discrimination criteria we have to treat both groups of neonates. few studies have focused on fa composition of surfactant pc in preterm infants before and after surfactant therapy. methods: tracheal aspirates were collected in venttlated mfants from birth until extubatlon ( / _ /twk ga, .+ g bw). after lipid extraction, t.l.c,, and methylation, fas of pc were quantified by gaschromatography. intralipid a ( . % linoleic acid, : • ) was started h after birth. results: six infants developed respiratory distress syndrome (rds) and received survanta r i mg/kg (sr), all doses within h after birth (ix s r n=l, x s r~ n= , x s r n= ). one child did not develop rds. in alt patients, the patmitate % in pc was ~ % (before sr<=natural composition), increased to ~ % after s r, and remained > % for i h after lx s a, . .+i . h after x, and . .+ . h after doses. in patients, intubated long enough, the palmitate % decreased with a half-life of . _+ . h to a new plateau which was still higher than baseline after week. linoleic acid % was . _+ . (with rds), decreased after s r~ and returned to baseline due to the decrease in patmitate %. thereafter the linoleic acid % increased linearly with . % per h, in patient even up to . %. other fas did not increase after return to baseline. in neonatal medicine the current parameters, arterial oxygen saturation and arterial oxygen pressure, are poor indicators for oxygen delivery and oxygen demand. the purpose of this study was to obtain venous blood samples from the inferior vena cava in stable neonates with respiratory failure and to determine a parameter that reflects more adequately the balance between oxygen delivery and oxygen demand. "l~e study included neonates requiring mechanical ventilation tbr severe respiratory insufficiency. an umbilical venous and arterial catheter were inserted in the inferior vena cava and in the aorta respectively. paired blood samples were obtained at the time that the patients were hemodynamically stable. fifty paired arterial and mixed venous blood samples were analyzed. jnear regression analysis showed the following correlations: in a neonatal intensive care unit adjacent to a delivery room caring for mothers per year, (with a referral of mostly for preterm delivery), virtually every neonate <ls g was seen by the same ophtalmologist, j.o. the incidence of retinopathy of prematurity (rop) was in - of ii cases ( preterms <ls g with % surviving to discharge, and % rop in survivors; % if less than weeks). in - , cases of rop were diagnosed by the same ophtalmologist. were born at less than weeks, of which ( %) survived to discharge, and among those survivors, rop was present in ( %), with rates varying from % at weeks to % at . objective: to compare a method of teicoplanine (teico) infusion using an electrical syringe-pump with a manual injection. methods: infusion of teico was simulated through a standart neonatal i.v. system. the infusion system consisted of an life care infusion pump (abbo'it lab.) with its i.v. set for maintenance intravenous fluid (flow < mi/h) connected to a -way stopcock. an meter extension tubing (vygon lab.) was placed between the stopcock and a neonatal catheter, an another meter tubing (injection tubing) was connected to the stopcock. the volume of the injection circuit was . ml. simulations were realised for weights ( or kg), with a doses of mg/kg and a injected volume of , ml to ml. our goal was to perform a complete infusion in minutes. we compare one method of infusion with an electrical syringe-pump with manual methods: a: teico was infused with a syringe-pump pilot c (becton & dickinson lab.) according to a protocol using ) a priming before connecting the syringe to the tubing (for immediate starting of infusion), ) a programmed volume injected in minutes (the drug volume was greater than the dose prescribed to avoid loss of teico into the syringe), ) a ml wash out was performed over minutes with the syringe pump. b: teico was manually injected in a few seconds in the tubing followed by a ml wash out over minutes. c: idem as b but a nu site valve (medex) was connected to the proximal end of injection tubing to avoid leakage between removal of the teico syringe and connection of the wash out syringe. during each run, serial samples were collected every ten minutes over a one hour period. the samples were assessed using hplc method. results: the amount of drug delivred at minutes was calculated and expressed as a perventage of the total amount of teico prescribed. results are a mean of to rons. a b c kg . + , % , + . % , -+ . % kg -+ , % -+ , % . -+ % conclusion: with a drug volume injected < circuit volume and a valve, a direct i.v. administration of the drug in the circuit followed by a wash out seems an accurate alternative to drug infusion conbroled by a syringe pump and is easier to perform. doxapram hydrochloride is a central and respiratory stimulant which is used in neonatal intensive care units to treat caffeine-resistant apnoes of the newborn. routinely, doxapram is administered intravenously. oral administration would be much easier but data on bioavailability after oral administration are limited (two studies) and show a large variation. we therefore studied the oral bioavailability of doxapram in preterm infants. doxapram treatment was started with an intravenous loading dose of , mg/kg during minutes, followed by a continuous infusion of mg/kg/h. after h the intravenous administration was changed to continuous oral administration with the same dosage, blood samples were collected h after both the intravenous and oral administration and analyzed by hplc-assay. apnoea rates per hours were listed before and after starting doxapram treatment. the median apnoea rate per hours declined from to after both the intravenous and oral administration. the oral bioavailability of doxapram is between and %, indicating that the oral route can be used effectively in these infants . there were no differences in the decline of the apnoea rate after intravenous versus oral administration of doxapram, infasurf r has been comnared with exosurf r in two studies: one as drodhvlaxis and the other a rescue trial. similar. althouah non-sianificant benefits were found for the natural surfactant. in trials there was a sianificant reduction in dulmonarv air leaks for . : % ci . - . for babies treated with natural comnared to svnthetic surfactants. for trials ( babies~ comdarina natural and synthetic surfactants for rds { comdarina survanta r and exosurf r. and one infasurf r and exesurfr% neonatal mortalitv was sianificantlv reduced (or . : % ci . - . with natural compared to synthetic surfactant treatment. in two further trials different natural surfactant drenarations were compared. reduced oxvaen needs for hours after treatment were found for r r infasurf and curosurf respectively when each was compared to survanta r. andarent lonaer-term benefits from these surfactants were not statisticallv sianificant. further trials will be needed to ascertain differences between various surfactant preparations. introduction bacterial meningitis is a common cause of admission in the paediatric age group, and one which still carries a high morbidity and mortality. these complications are strongly associated with a delay in antibacterial therapy. a significant proportion of these patients require mechanical ventilation; it is in this particular group of patients that survival is greatly diminished. the identification of risk factors for mechanical ventilation associated with bacterial meninges may help improving survival by shortening the delay to icu referral. the paediatdc risk of mortality score (prism) is the most widely used scoring system in the paediatric icu literature; the accuracy of prism on predicting outcome in meningitis has been shown to be poor. aim we aimed to describe our population of patients with bacterial meningitis requiring ventilation, and then to identify predictors of survival. methods this study was conducted at the baragwanath hospital in south africa which is an universityaffiliated institution with end average annual paediathc admission of patients. baragwanath icu admits non-neonatal paediatdc patients per year. a retrospective chart review from january to december of consecutive paedistdc icu admissions with bacterial meningitis was performed. results approximately cases of bacterial meningitis are admitted to the general paediatric wards every year; this constitutes ± % of all admissions. the mortality of these patients is + %. during this time ( m, f) patients ( %) were accepted for icu admission, with a mortality of . %. the median age was months (range days to years). the median delay to hospital admission was hours, and the median delay to icu admission was a further hours. the median duration of tcu stay was hours ( for non-survivors, for survivors). the main presenting features were convulsions ( %), altered mental state ( %), fever ( %), respiratory symptoms ( %), headache ( %), and diarrhoea and vomiting ( %). the most common indications for icu admission were seizures ( %), coma ( %), shock ( %), respiratory failure ( %) and acidosis ( %). in % of patients there was a cardiorespirstory arrest prior to admission. the most common organisms in the csf was pneumococcus ( %), haemophilus influenza ( %) and e coli ( %). the presence of leucopenia (wcc < ), a low platelat count (< ), acidaemia (ph< . ), and the need for inotropic support were strongly associated with nonsurvival. tachycardia and hypotension were not significantly essorjsted with poor outcome, as has been previously reported. discussion early diagnosis of meningitis and prompt institution of antibiotic therapy requires a high level of clinical suspicion. paediatric patients with bacterial meningitis that require mechanical ventilation have a poor prognosis. there is little evidence to suggest that nomsurviva[ can be predicted prior to icu admission, but a rapid deterioration requiring ventilation and inotrepic support with evidence of severe sepsis (low platelet count, leucopenia) is nmost invariably associated with a fatal outcome. the long term functional outcome of these patients make this disease even more devastating; the rote of icu in the management of these patients has yet to be fully estanished. objective and study design: a retrospective study was pertbrmed for all patients diagnosed with hemorrhagic shock and encephalopathy syndrome (hse) during to . soroka medical center is the only medical facility in the southern negev region of israel serving a population of - , residents, consisting primarily of jews and bedouins. results: patients ( bedouins and jews) were diagnosed with hse. main features on arrival included profound shock and coma with con~alsions. active bleeding and/or disturbing coagulation tests with falling heuroglobin levels and thrombocytopenia was noted in every case. all infants developed diarrhea shortly after arrival. elevated urea, creatinine and liver enzymes was noted in all cases. annual incidence tbr inlhnts < year of age was : , for bedouins and . : , for jews. patients ranged in age from - wks and arrived at the hospital late night/early morning ( : am-ll: am), during winter/early spring (november-april). all were healthy prior to admission, with short prodromal symptoms of upper respiratory tract or gastrointestinal infection noted in cases. most infants had markedly elevated body temperature on arrival. a history of overwrapping and/or excessive hearing was obtained in of infants. bacteriological and virological cultures were negative in all infants. one infant died and neurological sequelae were observed in all survivors. the high prevalence of hyperpyrexia during sleep in the presence of negative microbiological results with no evidence of excessive hearing, and the high incidence of rise among a closed, culturally isolated society known to have a high incidence of congenital malformations, may support previous assumptions that hse results from hyqperpyrexia, originating in most cases from a "physiologic" heat induced trigger which starts and peaks during the night in previously healthy infants with susceptible, predisposing genetic underlie. approximately % of hospitalised infants with respiratory syaacytial virus (rsv) infection require mechanical ventilation. our general practice is not to use specific antiviral therapy. we have undertaken studies of rsv-infected mechanically ventilated patients without underlying congenital heart disease or immunodeficiency. study i (n= ): a retrospective review of infants (mean post-conceptual age weeks; median duration of intubation was days (interquartile range - ). blinded review of chest x-rays during the first three days of mechanical ventilation revealed a spectrmn of lower respiratory tract findings from marked diffiase consolidation in all zones without hyper-inflation (n= ) to gross hyperinfiation without consolidation (n= ), with the remaining patients have an intermediate picture (n= ). death occurred only in patients who were at the poles of this continuum ( / consolidation and / hyperinflation). patients at these poles could be differentiated by gender predominance, birth gestation, alveolar-artarial (a-a) oxygen gradient (p< . l), oxygenation index (p< . l), peak inspiratory pressure (p< . ), and intubation days (p< . ). study ii (n= ): prospective audit of infants with the aim of verifying the above differentiation. separating patients based on their early x-rays and a-a gradient we confirmed the above predictable difference in duration of supportive therapy (consolidation v intermediate: ( - ) v ( - ) p< . ). severe lower respiratory tract rsv-infecrion in young infants results in different distinctive partems of disease with characteristic radiological and clinical features, and each has a predictable timecot~se. conflicting reports on special therapy should be interpreted with respect to these observations before making conclusions about the efficacy of any specific treatment. the clinical data of children wich suffered from a severe mycosis between jan. -dac. and wich were treated with amphotericin b in spanish hospitals were collected. mean age was + . years; were mate ( %) and female ( %). the most common underlying diseases were leukemimymphoma ( %) and congenital heart defects ( %). the major pathogens isolated were candida albieans ( %), other candida ( %) and aspergillus ( %). and liposomal amphotericin (la) in ( %). in the ca group, the starting dose was , ~ , mg/kg, reaching a maximal dose of . + , mg/kg after . + days. maintenance time was + days and the cumulative dose: ~ rag. in the la group, the starting dose was . ± mg/kg, reaching a maximal dose of . _+ . mg/kg (p< . ) after + days. maintenance time was ~ days (p< . ) and the cumulative dose _+ mg (p< . ). the reasons for la use were: elective in % of cases, previous renal failure in %, and ca inefficacy in %. hepatic or renal function impairment was two times more frequent in la group than in ca group, the antifungal efficacy was % for ca and % for la. therapeutic failure or toxicity induced withdraw of ca in % of cases, vs, , % for la (p< , ). mortality was not different in both groups ( vs. %), adverse effects were related to ca in events vs, only one in la group (p< , ). the commonest side effects in ca patients were fever ( %), chilis ( %) and nausea ( %). in ca group, cases ( %) developped analitical anormalities related with amphotericin, vs. cases ( %) in la patients (p< . ). in the first group, the commonest serum alterations were hypokaliemia ( %), raised creatinine ( %) and bilirrubin ( %). in the second one, hypokaliemia presented in % of cases (p< . ), raised bilirrubin in % and creatinine in % (p< , ), the antifungal efficacy of la is at least the same of ca. from the clinical and analitical points of view, la is much less toxic than ca. la can be used at a greater dose than ca and is safe in children with renal failure. laurence desplanques -serge gottot -christian dageville d~artement de sant~ publique -facult~ xavier bichat - rue henri huchard paris -france -the french << reaped ~> network was created to implement a nosecomial infections (ni) quality care program in nicu and picu, the first objective was to describe the annual ni incidence rate in each icu population : all patients stayed more than hours in icu. methods : n] criteria were defined by the reaped group according to cdc criteria. all data were collected by a medical and nursing team. all infection data were validated by an external investigator. results : patients were admitted over a months period. % were newborns. ni were identified among patients. the overall ni incidence rate (ir) was . % and . °/ person day (from . to . °/ according to age, lowest rate for newborns). septicemia ( % of ni) and pneumonia ( % of ni) were the two main ni. according to age, the septicemia ir varied from . to . °/oo catheter day (lowest rate for newborns) and the pneumonia ir from . to . °/ ventilator day (lowest rate for newborns). there were very few other infections (uti : %, ir : . °/ catheter day). gram positive cocci were isolated in % of septicemia ( % of them were coagulase negative staphylococcal). gram negative bacilli were isolated in % of pneumonia ( % of them were pseudomonas). % of ni were caused by candida, mostly septicemia. the septicemia and pneumonia ir varied according to unit even after adjustment for age. discussion the aminoglycoside antibiotics are frequently used in newborns for the treatment of severe infection and sepsis due to gram-negative microorganisms. the currently recommended dosage schedule for tobra ( . mg/kg q h) does not take into account differences in gestational or postnatal age during the first weeks of life. we questioned the validity of these recommendations and studied the population kinetics of tobramycin to establish predictive equations that enables the clinician to select the appropriate initial dosing schedule. methods tobra trough (t= ) and peak values (t= ) were taken on day - after birth in newborns. tobra was administered as a -minute intravenous infusion already in an adapted dosage schedule: . mg/kg q h in infants with gas < weeks; . mg/kg q h in infants with gas between - weeks and . mg/kg q h in infants with gas > wks, tobra concentrations were analyzed by tdx-assay, a one-compartment model was assumed and non-linear mixed effect modelling (using nonmem) was applied to the data, a trough level < mg/l and a peak level between and mg/l was required, with the present dosage scheme % of the trough levels were too high and almost % of the peak levels too low. calculations showed that the following dosage schedule should result in optimal levels of tobra. preterm infants gas < wks: mg q h preterm infants gas - wks: . mg q h preterm infants gas > wks: the currently recommended dosage schedules for toeira result in high trough and low peak levels. prolongation of the dosing interval and increasing the amount of drug per dose according to the above scheme will improve tobra level control. since january british clinicians have been conducting a randomized controlled trial of neonatal ecmo. mature infants (>- weeks gestation and birthweight kg) with severe cardiopulmonary failure have been randomized to receive continued care in their referring institution or referral to a designated ecmo centre for further management. we now present the preliminary results which have prompted closure of recruitment to this trial. the final outcome will be assessed as intact survival against death or severe disability at one year of age for all the recruited patients. patients were categorised by diagnosis such as isolated persistent fetal circulation, secondary persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia and by severity of illness at the point of first contact with the clinical coordinators of the trial -judged primarily by the oxygenation index ( before randomization). patients were randomized ( in each arm). hospital outcome data are reported for all patients and year outcomes on t ( survivors). at this stage of the babies allocated to ecmo are known to have died compared to of those allocated to conventional management (rr . ; % ci . - . ; p= . ). fewer deaths have been obsea-ved amongst ecmo allocated babies in all the diagnostic categories used. a % incidence of disability and impah~nent has been observed amongst survivors. this rate is similar in both groups and the survival advantage is not offset by an increased rate of disability or impairment following allocation to ecmo. we consider that these data combined with those available from other studies provide conclusive evidence that the survival to discharge from hospital is substantially higher in patients allocated to ecmo than in comparable infants not so allocated. therefore recruitment to this trial has been closed whist awaiting complete one year outcome data. sigston pe, goldman ap. #keating j. crook r. ~e dj~. great ormond street hospital for children nhs trust, and ~biochemistry department, kings college hospital, london, united kingdom. isoflurane is a safe and effective means of long term sedation in both children and adults in the intensive care setting. the use of isoflurane, by adding it to the sweep gas allows the use of this volatile anaesthetic agent in patients on ecmo, enabling rapid control and weaning of sedation. a potential problem with the long term use of isoflurane is fluoride ion accumulation with the possibility of renal toxicity, the purpose of this study was to assess plasma fluoride levels in patients receiving prolonged isoflurane on ecmo. method: fifteen infants and children (aged day - years, median weeks) receiving ecmo support for either cardiac or respiratory failure were recruited to this study. the patients were sedated with isoflurane as well as intravenous agents (morphine and midazolam). isoflurane was administered ( % - %) via a calibrated vaporiser to the sweep gas, adjusting the level to maintain adequate sedation. blood samples were obtained on a daily basis for plasma inorganic fluoride assay. the relationship between plasma fluoride and amount of isoflurane administered, as %-hours (vaporiser setting in % x hours) was calculated by linear regression. results: the duration of ecmo ranged from to (mean ) hours, during which the amount of isoflurane administered varied from to (mean ) %-hours. blood samples were anaiysed, demonstrating individual peak plasma fluoride levels of . to . #mol/ , mean , p.molli (toxic threshold = gruel/f). the plasma fluoride positively co;related with the %-hours of isoflurane (r = . , p = < . ). conclusion: this study shows that although there is a dose related accumulation of inorganic fluoride ions in patients sedated with isoflurane on ecmq, the peak fluoride levels are well below the suggested toxic threshold. merzel y, lev a, bar yosef g, halbertal m, lorber a ecmo center, picu, emek medical center, israel. the mortality rate of pediatric patients with acute myocarditis is - % according to the severity of myocardial damage. a month old gzrl presented with high fever, respiratory and cardiac failure. diagnosis of acute myocarditis was made and the patient was ventilated with high pressures and fio of . . she required high doses of inotropes. echocardiography revealed a dilated la and lv with severe mr. lvedd was mm and lvsf %. calculated oxygenation index was . she was resuscitated after a cardiac arrest. she was commenced on ecmo (using biomedicus centrifugal pump and avecor oxygenator) at a flow of ml/kg/mm with immediate improvement of hemodynamlcs, oxygenation and pc . resptratory assistance and vasoactive drugs were reduced. the patient was transported by air, on ecmo, to the ecmo cevter. she developed arf and cvvh-d was performed. cardiac fimction started to improve after days. ecmo was discontinued on day . echo revealed lvedd mm and lvsf %. ippv was discontinued on day . on discharge, a month later, her lvedd was mm and lvsf %. she behaves normally for age without neurologic or other medical sequellae. literature search revealed no case of acute myocarditis, as severe, that was treated successfully. survavors of disease this severe usually suffer dilated cardiomyopathy and permanent disability. the use of ecmo allows myocardial rest which prevents long term myocardial damage. introduction ecmo is increasingly used in the care of critically ill newborns. despite the frequent use of betalactam antibiotics in the treatment of these infants there are no data available on the dispbsition of cefotaxime (ctx) and amoxicilfin (am) d ring ecmo. the purposes of this study were to determine the pharmacokinetics of these two drugs in infants on ecmo and consequently formulate appropriate dosing regimens. we therefore studied the pharmacokinetics of ctx ( mg/kg ql h) and am ( mg/kg q h) in term infants on day after birth, blood samples were taken before (t-o) and . , , , , (am) and t h (ctx) after the intravenous bolus injection and analyzed by hplc-assays. . ctx mg/kg q h results in adequate serum levels of ctx in fullterm infants on ecmo, am mg/kg q h results in very high serum trough levels. recalculation based on the known volume of distribution and elimination serum half-life of these infants resulted in the following dosage recommendation: mg/kg q h. persistent pulmonary hypertension of the new-born (pphn) is characterised by rapid fluctuations in pulmonary artery pressure (pap) and a clinical impression of stifflungs. lung mechanics were measured in term infants, mean age . +_ . days who were paralysed and ventilated within the first three days of life. fourteen infants had pphn with systemic or suprasystemic pap measured by echocardiography. in these patients, the respiratory system resistance was . % higher (p < . ) and compliance . % lower (p = . ) during systemic or suprasystemic pap compared to when the pulmonary hypertension had resolved. in contrast, there were no changes in resistance in the infants with respiratory distress syndrome (rds) and no pulmonary hypertension or in the seven infants with normal lungs, where two readings were taken hours apart. the changes in lung mechanics interfered with mechanical ventilation, resulting in a . mmhg rise in paco (p= . ) during pulmonary hypertension. inhalation of nitric oxide ppm resulted in a % decrease in respiratory system resistance and an improvement in oxygenation. the bronchial and vascular smooth muscle was increased by % in postmortem lung samples from eight infants with pphn compared to six age matched post-mortem controls with normal lungs (p< . ). these findings suggest a co-constriction and co-hypertrophy of bronchial and vascular smooth muscle during pphn. anatomically the pulmonary vasculature and bronchi lie in close proximity to each other. thus mediators such as endothelin- released locally may act on both vascular and bronchial smooth muscle to produce the observed vasoconstriction, bronchoconstriction and smooth muscle hypertrophy. prince of wales children's hospital university of new south wales, randwick, n.s.w. australia. introduction an increasing mortality in asthmatic children has been reported. the increased severity of asthmatic illness leads to an increased demand for icu admission, and a corresponding increased need for mechanical ventilation. geographic end environmental factors are thought to be partly responsible for differences in disease sevedty throughout the wodd. for this reason, epidemiological studies from diverse areas are important, risk factors for icu admission, and for the institution of mechanical ventilation should be identified, to optimise icu admission criteria and to avoid unnecessary delays in admitting at-risk patients. aim to document the clinical characteristics of ventilated and non-ventilated asthmatic patients admitted to icu. methods this is a retrospective study of all paediatric asthma icu admissions from january to december . results there were patients admitted to the icu for acute severe asthma in the study period. the male:female ratio was : , the mean age . • . months, the mean prism . - . %, and the mean duration of admission . hours. there was no seasonal variation in admissions. only % ( / ) patients required mechanical ventilation. in % of all patients this was the first presentation with asthma. there were some significant differences between ventilated and non-ventilated patients (see table) . there was a significantly higher incidence of concomitant and nosocomial pneumonias in the ventilated patients ( . % vs . %) as well as segmental lung collapse ( . % vs . %). there were no deaths. discussion the need of mechanical ventilation significantly increases the morbidity of and duration of icu stay of asthmatic patients. younger asthmatic paediatdc patients have a significantly higher risk of ventilation. the need for ventilation is predicted principally from a worsening pco and respiratory acidaemia, which is often independently interpreted by the clinician as respira ory exhaustion. this study has shown that icu admission is important in the management of young paediatdc patients with acute severe asthma and respiratgry fa!!ure. intravenous salbutamoi in the emergency, department management of severe asthma in children. g.j.browne,a. perma,x. phung,m.soo westmead hospital, sydney, australia. it is postulate that if an initial intravenous loading dose of salbutamol is given in severe asthma, a more rapid clinical response will occur, reducing requirements for continued high doses of nebulised salbutamoi with fewer side effects. this double blinded study was conducted in the emergency department of westmead hospital a university hospital in sydney, australia. all children with severe asthma had initial nebuliser therapy ( rag of salbutamol with ml of saline). if asthma remained severe minutes later, they were given a dose of intravenous hydrocortisone ( mg/kg) and either normal saline or salbutamol microgm/kg intravenously. frequent nebulised salbutamoi therapy continued during the initial first hour if clinically indicated. continuous respiratory and haemodynamic monitoring occurred in the first hours. serum potassium and glucose determinations were made at study commencement and hour after intravenous therapy. salbutamol determination was made at study commencement. children remained clinically monitored for the next hours, with their ongoing treatment determined by clinical response. children with severe asthma months to years of age were studied, with given intravenous salbutamol and given intravenous saline. the intravenous satbutamol group (ivsg) showed rapid reduction in asthma severity scale in the first hours, with reduced need for high frequency nebuliser therapy ( _< hourly), occurring . hours.earlier. no clinically significant side-effects were found in either group, although, tremor more frequent in the [vsg. biochemistry and salbutamol concentrations were similar in both groups. the use of intravenous salbutamol (i microgm/kg) in the management of severe childhood asthma is a safe and effective therapy with no significant side-effects and the potential to abort severe asthma attacks in the emergency department. intravenous terbutaline in picu piva j., amantra s, rosso a., zambonato s, giugno k, maia t. introduction: the admission to a picu of children with respiratory failure secondary to an acute obstructive lower airway disease is a common event, especially during winter seasons. these diseases have several causes, but most of them (especially asthma and chronic airway disease) have a good response to the administration of b -adrenergic drugs. objective: to find the dosis of intravenous terbutaline that is safe, efficient and with minimal adverse effects when used in children admitted to a picu with acute obstructive lower airway disease and respiratory failure. material and methods: we study the records of all children that were admitted to our picu during the winter of . only the patients that had respiratory failure and acute lower airway disease and who needed the use of iv terbutaline were selected. the records were divided in two groups: less than months and more than a year old these two groups were compared in the following aspects: the minimal and maximal dosis, and the length of time of use of iv terbutaline, frequency of tachycardia, hypokalemia, and mechanical ventilation. to establish any difference in the two groups we use the t exact test of fisher and x , with p< . , results: during the period of study were admitted patients to the picu, and ( , %) of them used of iv terbutaline. the mean age was . + . month, used iv terbutaline during . + . days ( . to days), the initial rate was . + . p~g/kg/min, and the means of therapeutic dosis was . +l. ~g/kg/min (ranged from . to . ). twelve ( . %) patients had tachycardia art obstacle to the increases in the rate of use of iv terbutaline during any time. mechanical ventilation was necessary in patients ( . %) and ( . %) patients died. the children under year of age used initial dosis of iv terbutaline lower than the children up of year old ( . p.g/ kghnin x . ~tg &g/rain, p< . ), but without difference in the length of use, the maximal dosis, the rate of mechanical ventilation and tachycardia. the frequency of hypokalemia was most common in the group of children under year of age. acute respiratory failure during status asthmaticus may require mechanical ventilation. current therapy includes paralysis, pressure control ventilation (pcv) and permissive hypercapnia to limit pulmonary barotranma and its hemodynamic consequences. asthmatic children exert a significant amount of respiratory effort during exhalation. with paralysis, this expiratory effort is lost. unloading the inspiratory work of breathing while maintaining the patient's expiratory eftbrt using pressure support ventilation (psv), may be beneficial. methods: children receiving pcv (peak inspiratory pressure (pip) = kpa. rate breaths/min) and pco > kpa were switched to psv. children were initially ventilated with psv . kpa and peep = . kpa (servo c). all children received beta agonist therapy, ipratropium and anesthesia with ketamine or inhalational anesthesia, and were breathing spontaneously. respiratory parameters and blood gases are shown be~bre psv, within minutes (start) and when the ph had normalized (during). data are presented as median and range, * p < . compared to before psv. results: children with hypercarbia during pcv responded to psv, normalizing pcos and ph within hours. the mean respiratory rate decreased from a median of ( - ) to ( - ) while the pip was decreased to . ( . - . ) kpa within hours. the i:e ratio also significantly decreased. conclusion: psv permitted patients to active/y exhale while unloading the inspiratory work of breathing. perhaps this strategy shifts the patient's respiratory effort from inspiration to exhalation, thus permitting the child to meet the excess work of breathing caused by bronchoconstriction. maged z. youssef, peter silver, laura nimkoff, and mayer sagv. division of pediatric critical care medicine, schneider children's hospital, new hyde park, ny . introduction: mechanical vemiladon of patients with severe bronchospasm can be difficult, due to poor chest compliance and increased airway resistance. ketarmne is a cormnonly used anesthetic agent that has been shown to have bronchodilator properties. the purpose of this study was to determine ifa continuous infusion of ketamine had an effect on the oxygenation and chest compliance of children with severe lironchospasm who were mechanically ventilated. methods: a retrospective chart review was conducted of pediatric patients in severe bronchospasm who were mechanically ventilated in our picu and treated with a continuous ketamine infusion. all patients were receiving aggressive bronchodilator therapy and adequate sedation prior to keramine. patients were excluded if any new bronchodilator or sedative agents were started within hours of initiation of ketamine treatment. all patients were simultaneously treated with benzodiazepines. for each patient, the pao /fio ~ ratio and dynamic compliance [tidal volume/(peak imp. pressure -peep)] was determined immediately prior to ketamine, and at , , and hours post-ketsmine initiation. data are presented as mean ± s.d., and were a~yzed using one way anova and the multiple comparison method of bonferroni. patients (age . ± . yrs.) received * p< . ketamine for severe bronchospastu during mechanical ventilation in our picu. both . .xto-* * the pao /fio ratio and dynamic . . -.... . compliance increased significantly following initiation of the ketamine infusion (see figure) . the mean ketamine dose was ± mcg/kg/min, and the -, mean infusion duration was ± too-[/ hours. one patient required glycopyrrotate ~' to control excessive airway secretions, and " one patient required an additional dose of o--j i ~-~ ~/me diazepam to control hallucinations after i cessation of ketamine. all patients were t~n~,mr~ *~am~ successfully weaned off mechanical ~l~s ~,~s~on ventilation and discharged from the picu. conclusion: continuous ketamine infusion to mechanically ventilated pediatric patients with refractory broncliospasm results in a significant improvement in oxygenation and dynamic compliance of the chest. reports of adults with status nsthraaticus document significant morbidity and mortality, whereas studies in children have had more varied results. different centers report mechanical ventilation (mv) in to % of admissions, occurrence of pneumothoraces or paeutuomediastinums in to %, and mortality in up to % of patients ~'t . we retrospectively reviewed status asthmaticus admissions to the pediatric intensive care unit (picu) between january and december . seventy-five of these patients were admitted fr~an the emergency department of chla (er admit). the mean length of stay in the picu was . days and the mean length of stay in the hospital was . days. based on patients who had arterial blood analyses, patients had hyperoapnia (pco > ). all patients received oxygen, inhaled albuterol (alb), and cortieosteroid therapy. ninety-five percent of patients also received methylxanthine (mx) therapy. of the admissions, patients ( %) required mv. only of these patients were admitted through our emergency department, whereas the remaining patients were intuhated at outside facilities. twenty-three cases required intr:wenous beta-agonist therapy, either isoproterenol osop) or terbutaline (terb). h~ff of the ea.~es re~%wed were complicated with hypokalemia (k+< . ). c,', ,~lications ofpoeumothoraces or pneumomediastinums were seen in % of ,'r:u~ported patients, but in only % of er admit patients. only % of these were in mechanic.all, )atients. there were no deaths in the review. respiratory mechanics measurements 'are useful in mechanically ventilated children to optimize ventilator settings. nevertheless, the transducers used to measure flow (f) and pressure (p) remain expensive. objective. to evaluate the performances of piezoelectric p transducers ( us dollar) in measuring f and p. methods. we used a previously described monitoring system measuring respiratory parameters [ ] . in this study f was obtained by a differential piezoelectric p transducer (_+ . cmi-i , honeywell) whose sensitivity has been reduced to +_ cmh by an electronic amplification equipment and p by a piezoelectric p transducer (_+ (). cmhzo, honeywell) connected to a grid pneumotachymeter &nt) ffleisch or ). volume (v) ( to ml) obtained by numeric integration off ( . to l/rnin ) and p ( to cmh ) were respectively delivered through a calibrated seringe and an electronical manometer (pic premier) and calculated by the computer. bland and altman analysis was used for assessment of results bias. coefficient of repeatability (cr) was estimated by the standard deviation of repeated measurements of the parameters as calculated in a oneway analysis of variance. results. mean difference (mdi between injected v ( to ml) and measured v using pnt was . ml, sd = . ml. difference and mean v were not correlated. sd of repeated v measurements were not correlated to v. cr was . ml. mdif between injected v ( to ml) and measured v using pnt was lrd, sd = ml sd of repeated v measurements were not correlated to mean v. cr was ml. mdif between injected p and measured p was . cmi-i , sd . cm h sd of repeated p measurements were not correlated to mean p. cr was . cmh . conclusion. inexpensive piezoelectrical transducers can be used to measure f and p and evaluate respiratory mechanics in ventilated children. previous studies have already shown the problem of the reproducibility of pft in preterm ventilated babies. were studied preterm ventilated babies {mean weight gr) in the first week of life in clinically stable condition, measuring flow, airway pressure and esophageal pressure simultaneously. each baby was studied twice with an interval of one hour and each study was done increasing the rate till to inhibit spontaneous breaths. none sedative has been used. only mechanical breaths were analyzed. compliance and resistence were calculated with a computer system using the linear regression method. we expressed quantitatively the intrapatient variability as the percentage of variation of tidal volume, compliance and resistence between the two studies in each baby. then intraclass correlation coefficient test (icc) was applied to confirm qualitatively our results (total agreement = , good reproducibjtity > . ). we h~£ed, an a eept~ble ~efiabirl¢, ~-~r;= '~ . during mechanical ventilation, an air leak (al) and plateau phase duration (pl) may influence dynamic and static compliance (cdy and cst, respectively). this study evaluated the effect of al and pl on two methods of measuring c.dy and est. methods. intubated, ventilated patients in a pediatric intensive care unit were evaluated after obtaining informed consent. patients were intuhated with a cuffed endotracheal tube and ventilated with a serve ( ventilator. cdy and cst were determined using the serve ands~rmedics . objective: evaluate the repercussion in respiratory mechanics and arterial blood gases and the impact of the ventilator adjustments on the auto-peep magnitude. material and methods: the measurement of the auto-peep was performed using an eletronic-pneumatic controlled device with a oclasion valve installed between endotracheal canutla and the ventilator circuit. the d~'ice was connected to a solenoid to detecte the end of inspiratuo phase and thus, the activation of the oclusion valve. the signs of pressure and flow were monitorized using a diferential transducer and it was processed using a pc computer and tmeumoview® software. the stud were divided in phases: phase a. where the ventilator adjustments was performed using the routine of the unit and phase b, where the targets of mechanical ventilation were to minimize the auto-peep. static compliance (crs) was ineasured by the single-breath occlusion technique, using a mean of ten occlusions for analysis. passive respiratory resistance measurements and the tidal breathing flow-volume loops were also obtained., while the ventilatory settings were siguificantly reduced soon atier ecmo was started. before ecmo crs measured in all patienls was . _+t). ml/cmh /kg (mean_+sem). for each patient the ecmo course was divided into four periods, proportional to the duration of the treatment, and the best ~alue of crs in each period was chosen for analysis. as shown on the figure. crs significantly improved (*p< , ) from the second half of the ecmo course in the group of patient that finally were successfidly weaned from ecmo. no change ill compliance was measured in the group of patients who failed to respond to the extracorporeal hmg support our data suggest that compliance measurements during ecmo can be useful togelher with overall clinical evaluation to predict both outcome and duration of cxtracorporeai support in the neonatal and pediatric population. objectives: brain temperature determines the amount of neuronal damage caused by hypoxic insults. thus measuring brain temperature at standardised conditions is in request. we investigated whether brain temperature of neonates varies with head insulation environmental temperature, body activity and time course. patients and methods: we investigated non-invasive brain temperature analogues in healthy prematures tess than two weeks of age in an incubator (gestational age . + . wks; x + sd, weight + g). we measured nasopharyngeal temperature (tnasoph) by a thermistor placed in the nasopharynx via a feeding tube, zero-heatflux temperature (zht) at the temple by a thermistor and healflux transducer, insulated by two pads, as well as rectal and incubator temperatures. patient activity was documented by video taping. measurements were performed during periods of increased insulation ) by turning the head with its measuring site on to the mattress ( ( ) ( ) - ( ) ( ) ( ) ( ) . ( ) ( ) { ) ( ) ( ) - ( ) ( ) ( )i ( ) ( ) ( ) ( ) . ( ) ( ) t ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) web (lmg/kg) at rain ( ) - ( ) ( ) ( ) ( ) - ( ) the vehicle had no effect. paf caused dose dependent rise in ao and pa pressure and reduction in flow to lpa (up to % like the vascular endothelium, the endocardial endothelium (ee) has a significant impact on adjacent myocytes, and may critically alter myocardial function.~ we have previously shown that ee cells are capable of sensing and responding to hypoxia by the release of prostacyclin (pgl). potassium channels in other cell types have been reported to be oxygen sensitive. to determine whether potassium channels modulate the ee hypoxic response, we investigated the effects of three potassium channel inhibitors on hypoxia-induced pg] release from ee cells. methods: ovine endothelial cells were harvested and passaged onto ,~ microcarriers. cells were constantly perfused with normoxic and hypoxic kreb's solution, and with three potassium channel blockers: glibenclamide (gb, #g/ml), tetraethyl-antmonium (tea, ram) and aminopyridine ( ap, i mm), perfusate was assayed for prostacyclin (ria). data were compared by analysis of variance. * p<. compared to normoxic control; # p< . compared to hypoxic control. adrenaline is extensively used for resuscitation in neonates with rds. however, effects of adrenaline on systemic, pulmonary and cerebral hemodynamics have not been defined in newborns with rds. thirteen anesthetized, and ventilated newborn piglets were subjected to repeated saline lung-lavage series while mean systemic arterial pressure (abp), mean pulmonary arteriat pressure (pap), mean left atrial pressure (lap) and mean central venous pressure (cvp), cardiac output and blood flow in the internal carotid artery (ica) were measured. systemic vascular resistance (s~), pulmonary vascular resistance (pvr) and cardiac index (ci) were calculated. sixty minutes after luug-lavage, the adrenaline group (a) (n= ) received adrenaline as a continuous infusion of . lag/kg/mi, while the control group (c) (n= ) received saline. none of the varlables were changed by saline. however, significant increases in abp (p< . ), pap (p< . ), ci (p< . ) and svr (p< . ) were observed after administration of adrenaline, whiie pvr and ica were not modified. mean±sd for abp/pap (p/a), fvr/svr (p/s) and ci (ml/mirdkg) were: ratios of pap/abp and pvpjsvr significantly increased following infusion of adrenaline. these data suggest: ) the cerebral perfusion is preserved during the infusion of adrenaline; ) effect of the adrenaline infusion on the systemic circulation is more pronounced than its effect on the pulmonary circulation in newborn piglets with surfactant deficiency. s demirak~a, ch knothe, kj hagel, j bauer department of pediatrics, justus-liebig-university giessen, frg inhaled no is a short acting selective pulmonary vasodilator. we studied the effects of ppm no and % oxygen during heart catheterization in children (age - years, median years) with heart defects and elevated pulmonary vascular resistance index (pvri) in order to asses the value of no as a tool of decision making for corrective cardiac surgery. patients were eligible for testing when they were more than one year old and had a pathologically elevated pvri in a previous heart catheterization. intubation, 'anesthesia and muscle paralysis were performed in all patients during testing of pulmonary reagibility. calculations of pulmonary vascular resistance and flow were based on the fick method. response to no was assumed when pvri declined more than %, of the patients were responders to no. effects of no and oxygen on pvri, mean pulmonary arterial pressure (mpap) and pulmonary vascular flow (qp) in all responders are described in the table below. cardiac surgery was offered to all responders, and of them were successfully operated. surgery is planned in another patients and parental consent for surgery was not given in one patient. in ebstein disease, during the first days of life, the ability of right ventricle to propel blood to the pulmonary artery is impaired due to high pulmonary vascular resistances. the flow is mainly directed to left atrium through tricuspid insufficiency, right atrium and foramen ovale. to decrease pulmonary resistances and increase pulmonary blood flow, high frequency oscillations, mechanical ventilation, nitric oxide and prostaglandin are required. after few days, a forward circulation is normally established. we cared two newborns with ebstein disease where this approach was hindered by a large pulmonary valve insufficiency. both of them were diagnosed in utero, showing a large tricuspid insufficiency with a non opened pulmonary valve and a ductal left to right shunt. one fetus was hydropic. at birth, blood stream from the ductus arteriosus was directed to the right ventricle through the pulmonary valve insufficiency then to right atrium, left atrium and ventricle, aorta and ductus arteriosus. a low pulmonary blood flow was demonstrated by low mean velocities ( cm/sec). a high reverse flow was seen in descending aorta with a negative flow in the renal artery. both of these newborns were oliguric because of ductus arteriosus steal. pulmonary blood flow doppler evaluation allowed different strategies of ventilation, switching between hfo and conventional ventilation, modulation of pge doses, inhaled pulmonary vasodilators (nitric oxide) and surfactant. the hydropic baby died, the other survived after weeks of intensive care complicated by supraventricular arythmia (wpw). in conclusion, during neonatal period, in ebstein disease, a large pulmonary insufficiency leads to a vicious circle where lungs are excluded, inducing severe asphyxia and high pulmonary resistances. the blood is backward propeled from the aorta through the ductus arteriosus to the right ventricle and atria, then left cavities to aorta. arec must be considered when pulmonary blood flow does not increase despite optimal therapy. guti~rrez-larraya f*, mandoza a*, velasco jm*, zavaneua ( **, gatindo a ~, s&nchez-andrede r, s&nchez jl***, mellon a***, mar f***. pediatric cardiology*, pediatric cardiac surgery**, pediatric intensive care unit***. hospital de octubre. madrid. background: transesophageal pacing (tp) is effective and sate both for diagnosis and treatment of pediatric arrhythmias. material and methods. eleven consecutive patients are included. a tri or quaddpolar or f temporal transvenous catheter with an interpolar distance of to mm was advanced through the nares and positioned to the point with the largest amplitude of atrial deflection, surface ecg and a bi or monopolar electregram were recorded simultaneously, selecting filters when needed ( to mhz). pacing was performed with a programmable stimulator (medtronic ) beginning with ms and increasing ma to and then increasing up to . ms. narula method was selected to diagnose sinusal node disfunction (snd) and overdrive pacing to treat tachyarrhythmias. results. tp was useful in all the patients and no complications were observed: in patients a snd was diagnosed (one needing a definitive pacemaker), in two patients with atrial ratter (ripe ) sinus rhythm was recovered, in one patient with a postoperative junctional ectopic tachycadia we were able to get atrial synchrony with marked bemodinamic improvement, and patients with paroxysmal supraventricular tachycardia sinus rhythm was easily and quickly restored ( of them recquirad repited episodes of tp until pharmacelogycal levels of antiarrhythmic drugs were raised). mean age and weight were months and . kg (one patient had . kg). there was a close relation between height and depht insertion (r= . ). mean stimulation parameters were , ms and . ma. discussion. in experiencied hands tp is an effective and safe way to treat and diagnose cardiac arrhythmias even in newborns. it should be tried before endovenous pacing is stablished and it is faster than pharmacologycal treatment. bailing g., eicken a., sebening w., vogt m., schumacher g., bl~hlmeyer k.; kinderkardiologie, deutsches herzzentrum m nchen, germany to assess the outcome of balloon valvuloplasty in infants with cardiac failure caused by critical aortic stenosis a retrospective study was performed. between and neonates, aged - days (median d), weight .t - , kg (median , kg) with critical valvar aortic stenosis were dilated by balloon (aovp) as the first line treatment. patients received prostaglandin el, needed inotropic drugs and mechanical ventilation. associated cardiac lesions : persistent ductus arteriosus (pda) in patients (restrictive pda in cases), a mitral regurgitation (mivr) in cases ( severe and moderate or mild mivr), angiographic findings of endocardial fibroelastosis (efe) in patients, mitral stenosis (mivs) in , coarctation of the aorta (coa) in , and finally a small musculary ventricular septum defect (vsd) in i patient. vascular approach for ballooning : a. axitfaris in cases ( %) a. femoralis in t ( %) and v. femoralis in cases ( %). the median ratio between inflated balloon and aortic valve diameter was , . dilatation was achieved in all cases. the peak systolic gradient across the aortic valve (pre aovp) ranged from to mmhg (median mmhg) and was reduced to to mmhg (median ; gradient reduction is significant (p < , )). aortic regurgitation (aovr) was absent or mild in , moderate in and severe in patient after aovp. children survived (actual suwival rate: %; early mortalffy: n = ; late mortality: n = ). mid term follow up ( - , years; mean , years) showed an increase of the systolic peak doppler gradient across the aortic valve (median mmhg) but no increase of aovr. re-interventions (re-aovp: n = , commissurotomy: n = , mitral valve replacement n = , resection of subaortic stenosis: n = , resection of coarctation: n = ,vsd-closura: n = ) were performed in patients. rv contractility and pulmonary vascular mechanics(pvm) in immature animal models are poorly underslood. we developed an acute rv injury model to measure rv contractility and pvm in response to commonly used cateehalamines. ten anesthetized piglets ( - kg) were instrumented with micromanometers in the lv, rv, pa, and la. a pulmonary artery flow probe was placed to measure cardiac output(qpa). ultrasonic dimension crystals were sutured to the myocardium and dynamic chamber volumes estimated using shell subtraction methodology. rv injury was induced with - cryoprobe injuries at - to - °c for - minmes each. da at mg/kg/min, db at mg/kg/min, and ep at . mg/kg/min were infused in random order. rv contractility was evaluated by calculating a load independent measure of contractility, the preload recmitable stroke work(prsw), during vena caval occlusions. to describe pvm, input resistances), characteristic impedance(z ), total pewer(tp), and efficieacy f=qimo"p) were measured. measurements were made pre-and post-injury, during infusions, and between infusions. clyoablation decreased prsw ( . _+ . to . + . , p< . ). at the end of the experiment, prsw remained depressed to this level indicating stability of the model. one factor contributing to organ dysfunction for infants undergoing repair of congenital heart defects (chd) is their "inflammatory response" to cardiopulmonary bypass (cpb). this response is characterized by an increase in cytokine release, complement activation and endothelial injury. modified ultrafiltration (muf) is a method for removing tissue water and inflammatory mediators by rapid ultrafiltration followin~ cpb, muf may acutely improve post-operative end organ function. in this study, we evaluated the effects of muf on the pulmonary and cerebral function of infants undergoing cpb for repair of chd. we prosnecrivety randomized infants (.~ mos) to either muf (n= ) or no muf (n= )(control) following correction for chd. the study intervals were ) before cpb, ) immediately after cpb, and ) minutes after cpb. pulmonary function was evaluated by measuring dynamic compliance (cdyn) and airway resistance (raw). for pts (mue= pts; control= pts) exposed to a period of deep hypothermie circulatory arrest (dhca), cerebral metabolism (cmro ) was calculated at each interval using the xe clearance technique for cerebral blood flow measurements and arterial and jugular bulb saturation measurements to calculate cmro . a reduction in cmro has been consistently demonstrated after dhca. the effects of muf on cdyn and on cmro are shown below: p< . vs pre-cpb; # p< . vs post-cpb • p--o. vs. post-cpb this study demonstrates that immediately following exposure to cpb, muf will improve pulmonary compliance. raw was not different between groups. there was no significant difference in hours of post-op ventilation for either group. in those pts exposed to dhca a trend towards better cerebral metabolic recovery compared to control was demonstrated. this is the first technique applied to infants undergoing dhca where cmro after cpb was greater than precpb measm~s. although this may be beneficial to postoperative hemodynamics, ventilatory management and long-term neurologic recovery, more patients and longer follow up will be necessary to verify such an effect. the effects of conventional mechanical ventilation (cmv) on left ventricular (lv). diastolic filling in neonates are not well established. one approach to improve lv filling is the use of cmv to provide a phasic increase in airway pressure {thoracic augmentation). this phasic increase in airway pressure may result in an increase in lv filling similar to that which occurs with cpr. thoracic augmentation has not been evaluated in neonates with ventricular dysfunction who frequently demonstrate increased heart rates. attempts to maintain low peak airway pressures during cmv may result in a prolonged inspiratory time that occurs over multiple cardiac cycles. this may alter lv filling in the later cardiac cycles. to determine the effects of inspiratory time on lv diastolic filling, infants were examined with doppler echocardiography less than hrs after surgery for the arterial switch procedtme. pulsed doppler recordings of the millal valve (mv) were obtained with the inspiratory time adjusted to occur over cardiac cycles ( sec.). a pressure transducer was placed in line with the ventilator, and the respiratory cycle was recorded superimposed on the doppler tracing to provide accurate determination of inspiration and expiration. doppler recordings were obtained from the apical -chamber view and the following measurements were made: peak e and peak a velocities, eia ratio, and deceleration time. compared to the expiratory phase of cmv, the initial beat during the iuspiratory phase of cmv resulted in an increase in mv peak e (. +-. vs . -+ . m/s, p< . ) and peak a (. + . vs . -+ . m/s, p< . ) velocities with no change in mv deceleration times (p<. ). compared to the initial beat during tile inspiratory phase, the third beat during the inspiratory phase resulted in decreased peak e (. + . vs . + . m/s, p< . ) and peak a (. + . vs . + . m/s, p< . ) velocities with no difference in deceleration times. thus, cmv augments lv filling during the initial phase of inspiration. however, as the increase in airway pressure is distributed over multiple cardiac cycles, lv filling falls below baseline levels. these observations indicate that while thoracic augmentation may be beneficial, to optimize lv filling the inspiratory time of cmv must be < cardiac cycles. energy expenditure in pediatric orthotopic liver tranaplantat~on, to determine the actual calorie requirements of critically ill children and evniuate the correlations between measured, stress-p~lictod and repleted energy exponditttm and the severity of illness. des/gn: a prospective, dinlcal study. se~ng: tertiary care pediatric icu in a university hospital. patients: ten patients aged to months with disorders prompting picu admission, including sepsis, respiratory failure, solid organ transplantation, and cardiovascular surgery. inta~entions: all patients were studied within hrs of major surgery or transplantation, or following acute illness. all patienls were severely stressed clinically and all but two were intubated by cuffed tubes, in three of them, still in a stress state, the study repeated on the third day of the disease, energy expenditure mensurements (mee), as well as illness seventy scoring systems, mtfltisystern organ failure scores and various anthropemetric and clinical indices of nutritional status, the stress-predicted energy expenditure (s-pee), the basal metabufie rote (pbmr), the repleted energy (re) and the recommended dietary allowances (rda) were measured or calculated in each patient. multiple regression analysis was used to analyze the data. measurements and main results: although the mean mee was significantly lower than the mean s-pee ( . + kcal/kg/day vs. . : kcal/kg/day, p<. ), it did not differ significantly from the pbmr (mean difference - . kcal/kg/day, range - . to + . kcal/kg/day). the s-pee/mee ratio ranged from . to . , while the re/rda ratio ( . : kcal/kg/day)/( . : kcal/kg/dny) ranged from only . to . . the prism/tiss ratio was not correlated better with mee than the diagnostic category (r~=. vs.. , respectively). the re was positively correlated withthe mee (rz=. , i)=. ) while negative oarrelatian has been found between mee and age, mid-arm circumference, triceps skinfotd and the use of vaseactive agents (r~. , - , -. , p<. and -. resp~lively). concl.m~: if s-pee is used for caloric repletion in the stressed oritic~ly fll el~d, these patients will be substantially overfed by as much as %. although pbmr appears to approximate the mee by ± %, other clinical and nutritional indices should also be ennsidered. objective: to deter .mine..t.he metabpli.c and.nutritional state of mechanically ventilated intants and children m relatmn wlm severity or msease. patients and methods: mechanically ventilated infants and children, median age months (range days to years), were studied. severity of illness was assessed using prism, prism-ii~ and fiss-scores. oxygen consumption (vo ), energy expenditure (mee) and respiratory quotient (rq) were determmed by mdirect calorimetry. total urinary nitroger(tun) and creatinine excretion, levels of albumin and crp were aetermmed in patients. in these patients daily caloric intake and substrate utilization were assessed. they were categorized in subgroups: a partial feeding (recent admission to p cu); b complete feeding. results: mee of the total group (n= ) a) i=intake g/kg/day (% total intake); u=utilization g/kg/day (% total production). nitrogenba]ance was negative in all patients in group a (mean - . -- : mffkg/day) and positive in all but one patient in group b (.mean . ± .d n~g/..kg/day;p= . ). no significant correlations were round between creatinine height index, crp, albumine, jun vs v u /kg conclusions: the mean measured energy expenditure does not exceed predicted resting energy expenditure, but ~ere is a wide range. in a majority ot patients with complete feeding h.igh carbohydrate intake resulted, in high kq and lipogenesis. in patients witla partial teeding the highly negatwe nitrogen'balance suggests that in the early phase of diseasean higher protein intake should be provided. severity of illness scores ann oiocnemicm markers of physiologic stress correlatedpoorly with oxygen consumption. leite,hp; iglesias, s; faria, c; ikeda, a; albuquerque, mp; carvalho, wb pediatric icu -s~o paulo federal university -s~o paulo, brazil objectives: ) to evaluate patterns of use and monitoring of nutritional support in critically ill children; ) to evaluate an education program in nutrition support given throughout the resident physician training in the pediatric icu. patients and methods: records of patients receiving nutritional support during were reviewed. aider this first phase, knowledge and understanding of the role of nutrition support was conveyed to the residents through didactic lectures. in a second phase thedata were reevaluated in children who were given nutrition support in . results: from a total of days ofthempy, the single parenteral route was utilized in , %, the digestive route (tube feeding or oral route) in , %. of this time. a previous nutr~ional assessment was performed in children; no patient had the nutr~on goals set. the nitrogen to nonprotein calories ratio ranged among : and : . only , % of the patients had their estimated caloric needs supplied and this goal was achieved only in those patients who were on enteral tube feeding. patients did not achieved their goals for vitamins. the supply ofoligonleme~s was adequate except the zinc. nutritional monitoring parameters including weight, serum albumin and serum triglycerides were performed in almost all the patients but without uniformity. the reevaluation ofthase parameters showed adequacy of protein and micronutrients supply; however deficiency in nutritional monitoring and infrequent enteral feeding were still detected. conclusion: there were lacks in the implementation of nutritional support, which were partially corrected in the rid phase of the study, although the training of residents may have contributed to give them cognitive skills, it didn't changed policies and procedures as desired. we recommend reinforcement of the education program concerning basic nutritional aspects, and the organization ofa multidisciplinary team in charge of coordinating the providing of nutritional support. plasme free fatty acids (ffa) are the meier energy source for mast tissues. during fasting ffa are released from the breakdown af triglycefides in edipose lissue (at). lipalysis, le. the rote of release o/ ffa, has been megsured in humans by means of stable isotope techniques using labeled pa or glyeerd as traces. no information is avoilob!e io dale on the ro of la. we infused albumin hound u c-pa and u c-la in critically ill infants, receiving kcel/kg/doy of iv glucose end na oral feeding (weight . ,i., kg;, range . - . ; ego : days, range ) and measured simultaneously the ra of pa and la from (he isotopic enrichment of plasma fea by gas chromatography-mass speclrome|ry ai : , : and : hours from tile shod of the infusion. a subcutaneous gluted at biopsy was obtained far fatty acid (fa) composition. we intended to ( ) in fie infants sbjdied atipa ~'os hi her than attla (~p<o.o )' and ihe ra of pa was higher then thai of la (~p= . §). however the ratio el the re's to the respeclive fa in at was higher for la than far pa (*p= . ). in conclusion the ra af la was higher then expected from ~he fa composition of at. we speculate [hat la is preferentially released during tipolysis and its contributuion to the energy metnbolism of the sick infonl could io !orger than what: is normai!y assumed from ihe fa composilion of at and of plasma fea. preoperative starvation can be prevented in infants undergoing non gi surgery by continuing feeds till as long as it is safe to do so. some gi disorders require withholding of feeds for a long period. for these and for infants already suffering from pem~ parenteral feeds are given preoperatively. peroperatively nutrition is maintained by ensuring adequate glucose supply in the infusion fluid and its smooth metabolism. proper placement of feeding tubes are also carried out peroperatively. postoperative early resumption of oral feeds is ensured by new techniques of anaesthesia and pain relief and methods to ensure early return of peristalsis. enteral feeds of pre digested substances and feeds through transanastomotic tubes and through gastrostomies and jejunostomies can prevent starvation in many situations. parenteral feeding is carried out only when enteral feeding is not possible, for example in necrotising enterocolitis~ gastroschisis, short gut syndrome, high enteric fistula and acute pancreatltls. the artedal ketone body ratio (akbr) is established as a valuable tool in the management of adult patients undergoing surgery for severe liver disease.the redox theory emphasises the central role of the liver in preserving homeostasis and the importance of the hepatic mitochonddal redox potential (nad+/nadh) in monitoring liver function and integrity.the akbr (plasma acetoacetate/ hydroxybutyrate) is a measure of hepatic mitochonddal redox status, reduced ratios associated with poorer outcome. the venous ketone body ratio (vkbr) is influenced by peripheral ketone utilisation and therefore thought unreliable in assessing hepatic redox its use has been dismissed as no correlation with the ratio in hepatic venous blood was found. inspite of this. vkbr is used in the diagnosis of lactic acidoses and respiratory chain defects. the objective of this study was to determine the relationship between the akbr and vkbr in a paediatnc intensive care population. children admitted to the paediatdc intensive care unit, with indwelling arterial and central venous lines as part of their routine care, were recruited for the study. the median (range) age was . years ( - . years) with prism score ( - ), simultaneous akbr and vkbr were measured. suppression of ketogenesis was confirmed using a rapid -hydroxybutyrate strip test (ketofilm, genzyme diagnostics) pdor to sampling. the median vkbr . (range . - . ) was lower than median akbr . (range . - , ), there was good agreement between artedal and venous ratios, bland-altman analysis giving a % confidence interval for relative bias of - . to - . . there was a significant correlation between vkbr and akbr r , , p, . (intercept . , slope , ) conclusions; values for akbr tend to be higher than vkbr, however there is a consistent relationship in critically ill children. in paediatdc patients in whom ketogenesis is suppressed, vkbr may be considered equivalent to akbr. this simple test may prove to be a useful adjunct in predicting mortality in cdt{cally ill children. to understand the present status of pediatric intensive care in china, we conducted a survey between october and december, , involving hospitals in provinces and municipalities. the results showed that there were totally icus for pediatric patients, including pediatric icus (picu), neonatal icus (nicu) and pediatric surgical icus (sicu), with total of beds. the physicians to bed and nurses to bed ratios were : . and : . respectively. the average number of equipment per bed was . ventilator, . multi-fnnction monitor and . infusion pump. very few of the icus had portable x-ray machine, biochemical and blood gas analyzers, and hemodialysis machines. the most frequently treated diseases/conditions were pneumonia, intracraniat infections, post-operation and sepsis in picus, and neonatal pneumonia, hypoxic ischemic encephalopathy and sclerema in nicus. pneumonia and respiratory failure accounted for . % and . % of all the diseases/conditions treated in the icus and the mean case fatality rate of respiratory failure was . %. the results of the survey suggest that there is shortage of tcu beds and modern equipment, and treatment is often delayed due to excessively strict criteria for mechanical ventilation. a set of simple, and nationally acceptable criteria for evaluation of severity and cure of the diseases/conditions is urgently required. the medical reports of children were reviewed and each admission was analysed in terms of age, sex, diagnosis, management within the hosp~al, length of hospital stay and type of poisoning. the youngest age was days and the oldest was years. hundred and twelve ( . %) of the children were girls and ( . %) were boys. the most common ( . %) reason of admission was intoxication among all of the cases and the greatest group ( . %) of the poisoned children had ingested medication which was followed by another group of patients ( . %) who had eaten mushrooms. the peak incidence of drug ingestion was salicylate intoxication ( %). forty drug poisoninigs were accidental while was intentional. the majority ( . %) of the cases that committed suicide was between and t years old, and the main cause of suicide was being unsuccessful at school. we conclude that poisoning -especially salicylate intoxication -is still a major problem in turkey and we believe that emphasis on the need to stere all kinds of drugs in a secure place and re-examination of a chin resistant packaging should help to reduce childhood poisoning significantly which is a preventable condition. included were all patients who died in the hospital, except those treated in the neonatal icu (predominantly premature and sga newborns) and those who died in the emergency room. among a total of hospital admissions (excluding the neonatal icu and emergency room), patients died ( . %). of these patients ( %) died in the pediatric icu, ( %) in the ward and ( %) in the operating room. a chronic underlying disease was present in ( %). withholding or withdrawal of therapy was implemented in ( %) children, ( %) died due to failed cpr, ( %) were brain dead and ( %) died following a dnr order. justification for therapeutic restrictions in the patients of the dnr and w/w groups was imminent death in ( %), lack of future relational potential in ( %) and excessive health burden in ( %). withdrawal or withholding of therapy was carried out by extubation in %, vasoactive drugs were stopped in %, and mechanical ventilation was withdrawn in %, analgetics and sedatives were frequently used (in % and %, respectively). hence decisions concerning restrictions of treatment are common in pediatric practice, mostly due to imminent death. patients in which treatment was restricted were characterised by a longer hospital stay, a worse prognosis, a higher frequency of chronic underlying diseases and a lower acute mortality risk. despite restrictions of intensive therapy, most patients were allowed to die in the pediatric icu. background microalbuminuria (mca), a subclinical increase in urinary albumin, reflects glomerular and overall vascular permeability " . an increase in urinary excretion of albumin occurs after burns and trauma. transcanillary albumin escape rate is also increased in response to elective surgery and in critically ill adult patients . we investigated a possible relationship between urinary albumin levels and clinical instability, as measured by pediatric risk of mortality (prism) scores. method we studied consecutive patients (median age of months, range - ). patients whith nephropathies or any abnormality of urine analysis were excluded from the analysis. prism scores, mca (mg. - ) (immunonepbelometric) and urinary creatinine (cu) (mmol.l -!) (jaffb) ( hour collection sample) were determined within hours from admission to the picu. the mca/cu ratio (mg.mmol. "l) was used to correct for urine output variability. diagnoses included respiratory failure ( ), postoperative ( ), neurologic ( ), sepsis ( ), trauma ( ) and miscellaneous cases ( ). pearson's correlation was performed to correlate data. results and conclusions. mean prism score and mca/cu were . ± . sd and - sd, respectively. a significant correlation was found between mca/cu and prism scores (r= . , p< . ). our observations show that, independently of the initial insult, the paediatric unstable patient may have increased capillary permeability, which is correlated with the degree of physiological derangement, as measured by prism scores. microalbuminuria can be rapidly determined since it is routinely used in the management of diabetic patients, it is inexpensive, simple to measure and blood-spearing. therefore, it might have a role in the clinical assessment of capillary permeability and transcapillary albumin escape worldwide the demand for paediatric intensive care services exceeds the supply. in developing countries sporadic access to such services alters expectation of care and can lead to children being either mechanically or handventilated in general paediatric wards. the outcome of children requiring ventilation in a major teaching hospital in india was reviewed.children were ventilated on an adult intensive care unit (aicu) if a bed was available, otherwise in the general paediatric wards. over a year period children were ventilated on aicu with deaths. yearly mortality rates varied between - %. over a month period patients were ventilated on the paediatric wards. of the p~tients over weeks of age died (chi squared .t >p> . ) reasons for the higher mortality rate on the paediatric ward likely include the higher patient:nurse ratio, and more limited resources. a predictor of mortality based on simple physiological observations without the need for expensive blood tests and including chronic health status would be a useful tool. the establishment of a paediatric intensive care unit is proposed to redress the balance of care. to assess the performance of the pediatric intensive care unit of hospital dona estef~nia by an international standard score, the authors did a prospective study of consecutive admissions to the unit during a period of months. mean age was . _+ . months; mean lengh of stay was . + . days. the effectiveness and efficiency were determined by the admission prism. admission efficiency was defined by two criteria: a) mortality risk > % or b) the administration of at least one intensive care unit-dependent therapy. the cumulative observed mortality was . % and the expected mortality was . %, with a standardized mortality ratio (smr) = . . the overall performance of the prism score-based predictive model was found to be good (goodness-of-fit test x [ ] = . ;p= . ). of patients admitted, combining the two criteria (icudependent therapy and mortality risk) an admission efficiency of ( . %) was found, equating to ( . %) of cu days. conclusion: in our study the assessment of the admission efficiency and of the effectiveness of the unit was possible by using the prism score of admission. there was no significant difference between mean values for otiss and ntiss)in level l patients (p= . paired t-test).for level and patients mean value of ntiss was greater than otiss (p< . ). there was a significant correlation between levels using either ntiss or otiss (mean difference level and , level and , ( p < o.oool). conclusions: a new tiss has been developed and used in a picu. nurses were able to accurately score the interventions on their shift. the assignment of patients to intensive care levels correlates with tiss values allowing a quantitative measure of severity. objective : to compare the rate of cerebral palsy (cp) between monochorionic-twins, dichorionic-twins and singletons born at to weeks' gestation. design : two-year prospective cohort study. setting : geographically defined study (region of franche-comt~., france). main outcome measures : type of plasentation was obtained by anatomopathological, or macroscopic examination of placenta and comparison of twins' blood-groups. neurological assessment was performed at two years of age (uncorrected for gestational age) by family doctor (pediatrician or physician), or neonatologist of the icu at tertiary center. sample : of i survivors aged of two years ( % follow-up rate), born between / / and / . triplets and chromosomic malformation were non included. results : thirteen ( %) of the singletons had cp.vs / ( %) of dichorionic twins and / ( %) of monochorionic twins (p= . ). four of the monochorionic twins ( %), / dichorionic twins ( %) and / ( %) nngletons suffer from quadriplegia (p< . ).in a multivariate approach, monochorionic twin placentation was the strongest risk-factor of cerebral palsy (or= . , ic % = a- , p< . ). others risk-factors of cp were : lack of father's profession (or , p< . ), maternal antecedent of abortion (or . , - , p< . ), vaginal delivery (or . , - , p< . ), hyaline membrane disease (or . , . -t , ~ . ). discussion : this is the first population-based study to uplight the role of monochorial twin-placentation as a strong risk factor of cp for premature infants. cp is more severe in monochodonic twins than in other infants. mecanism of cerebrat deficiency is not clear since none of our infants with cp was survivor of an in utero cotwin's death, and none of these infants was exposed to twin to twin transfusion syndrome. were these monochorionic-twins affected by an undiagnosed neurological structural defect that could lead both to prematurity and handicap remains an open question, a vital role of the intensivist is to ensure that knowledge and practice are imparted to trainees in the icu so that patients receive optimal care. teaching effectiveness varies widely leaving gaps in knowledge and practice in the trainee. being an effective teacher should not be a "gift" of a privileged few. the icu provides a fertile ground for using a variety of methods for teaching, e.g. didactic, at the bedside, emergencies, and in the performance ofproeeaures. in this environment, much can be learned. we have embarked upon a program to facilitate this learning process. i) teaching needs to be recognized as the foundation of good clinical care, i.e., patient related, and in its ability to generate discussion and research investigation. ) teaching structurally has many components including the speaker, audience, varying situations, and the message delivered. ) establishment of a program using these components to enhance teaching abilities at all levels, a) evaluate base-line teaching skills initially, b) individualize interventions to improve teaching skills, e) demonstration of learned skills with re-evaluation. this process is analogous to the analysis of a clinical disorder in a patient which, once recognized, interventions are then instituted and then re-evaluated. ) instill the desire to use these attained skills to teach and interest others to teach. teaching excellence should be recognized through awards, honors, and academic advancement. a major emphasis of this program is to provide participants with skills necessary to teach thought processes, decision-making skills (what to do, what to avoid) and implementing appropriate management during stressful emergency situations common to the picu. introduction: many" e-mail based discussion groups exist on the internet to provide medical professionals with a rapidly responsive medium for the international exchange of ideas relating to patient care. several such lists each serve more than a thousand professionals in more than countries, each distributing a dozen or more messages each day to every subscriber. there is very little known about the time being spent by professionals interacting with these lists, and very little known about the impact of the discussions on patient care. we wished to test the hypothesis that these discussion groups provide infortuation which is being used to change the care of individual patients and the general approach to patient problems. methods: in early january a pilot electronic survey was sent to a small fraction (n= ) of the memberships of e-mail discussion groups, picu@its.mew.edu, and nicu-net@u.washington.edu (the full memberships of both. groups (n=t for nicu-net, n= for picu) will be surveyed in early february of ). participants were asked for demographic information, experience and skill level relating to e-mail, time spent with the discussion groups, perceived usefulness of different types of discussions, and the ways in which the discussions were used clinically. the pilot study was analyzed for construct validity by correlating an overall assessment question with a summary of the specific questions. scale reliability was measured by cronbach's alpha statistic. results: the pilot survey response rate was ( %). the majority of respondents were male physicians, with an average age of +_ years, who had completed subspecialty training in intensive care, and were working at a university-affiliated hospital. most had been using e-malt for more than months, and considered themselves moderately adept in that use. % felt that the list helped weekly to keep them informed about current issues and practices in their field(s), and % felt that, at least monthly, they used information from the list(s) that was not readily available in medical journals. overall, % agreed that the list improved their professional competency. when asked to compare the value of months of membership on an e-mail discussion group with more traditional educational media, % compared it with attending a national conference, and % compared it to a journal subscription. cronbach's alpha was . , construct validity testing yielded coeff=. , p <. . conclusior~: internet-based e-mail discussion groups for health care professionals can be an important part of a strategy for maintaining professional competency. despite the very low cost of this medium for most, the value is felt to be comparable to that of t~r more expensive forums for education. further study will include distribution of the full survey in early february of . fronk shann, tony slater, gale pearson and the pim study group we have developed a new score for predicting the risk of mortality in children admitted to intensive care. the score is calculated from only seven variables collected at the time of admission to icu: mechanical ventilation (yes/no), booked admission after elective surgery (yes/no), the presence of any one of specified underlying conditions, both pupils fixed to light (yes/no), the base excess, the pao divided by the fio , and the systolic blood pressure. most scores used to predict outcome in intensive care require the collection of a large number of variables (so many icus do not calculate them routinely), and they use the worst value of each variable in the first hours in intensive care. this means they appear to be more accurate than they really are (about % of child deaths in icu occur in the first hours -so they are diagnosing these deaths rather than predicting them), and they blurr the differences between traits (a child admitted to a good unit who recovers will have a low score; but the same child who is mismanaged in a bad unit will have a high score -the bad unit's high mortality rate will be incorrectly attributed to its having sicker patients). pim was developed in the picu at the royal children's hospital in melbourne, and has been tested in six other picus in australia and one in the uk. objectives: to study the characteristics of the muhiorgan dysfunction syndrome (mds) in children. methods: a retrospective study with all the children with mds diagnosed from january to june is presented. children fulfilled the wilkinson criteria (i). in all of them the number of organs affected and the prims score were determined during the first hours. several groups were performed according to the clinical diagnosis, the hospital of origin and the order of organs affected. results: the subjects studied were an % of the pediatric intensive care unit admissions. of them expired ( %). no differences in age, sex and weight were observed between the children dying and the survivals. the most common causes of mds were sepsis, both nosocomial ( %) and medingococcal (i %) and acute respiratory failure. sixty-fivepercent of the patients were from the hospital wards and the remaining were directly admitted to the pigu from the emergency room. the systems affected were: respiratory ( %), cardiovascular ( %), hematologic ( %), central nervous system ( %), renal ( %) and (hepatic) liver ( %). the organs initially failing were: heart ( %), tung ( %) and central nervous system ( %). the children dying had a larger number of organs with failure than the survivors ( . v,s. . , p< . ).the prmis score was higher in the children expiring than in the survivors ( . v.s. , p < . ). s.mmary: the mds is a common pathology in picu, with a high mortality, the mortality is higher in children with a larger number of organs affected and a higher prism score. sepsis is the most common etiulogy. methods : from june ist to july th , all patients admitted to the pediatric icu were included. the score was measured at day (d ) and day (d ) and we used variables. for each organ system, we defined categories : dysfunction or failure, which we respectively confered or points. results : patients were admitted : newborns, children. were medical and were surgical patients. ( %) patients had two or more organ failure at the admission, ( , %) patients died, which ( %) in the first hours. the mortality rate was the same for children with two or more organ faiiure at d and d : / ( , %) at d , / ( , %) at d . the mean score is different for children who survived or who died : , versus , at d ; , versus , at . when the score is > , the mortality rate is significant. conclusion : in this study, there is a good correlation between the score of severity and the mortality rate but we have few included patients. we need a prospective multicentric study to assess these results and we must compare this score to other scores of severity used in picu. back.qround: injury to the central nervous system is the cause of death in the majority of pediatric trauma victims, studies have identified a wide range of factors associated with poor outcome from brain injury. however, when single features are analyzed, they are not sufficiently accurate predictors. few studies have used a multivariate analysis of these factors and pediatric outcome, methods: clinical and radiographic features of comatose children after traumatic brain injury were analyzed, clinical parameters, the initial cranial ct scan, and demographic characteristics were analyzed for an association with death or vegetative survival at months. a tree diagram in which risk factors may differ within the study subpopulations was constructed using recursive partitioning. results: chitdren with a motor score _< had an -fold increased risk of poor outcome compared to those with motor scores > . among patients with scores of _< , those with abnormal pupillary reflexes experienced a -fold increased risk of death compared to those with normal pupillary reflexes. among patients with a motor score > , an intracranial diagnosis code (no pathology, mild shift _< mm, swelling, shift > mm, surgical mass lesions, or non-operative mass lesions) was highly predicative of poor outcome at months. children with ct findings other than normal or mild swelling had a -fold increased risk of poor outcome. of children with swelling, shift or mass lesions, the pupillary light reflex was associated with outcome. children with abnormal pupils had a -fold increased risk of poor outcome. discussion: a few clinical and radiographic features stratified comatose children into fairly distinct risk groups. information available early after traumatic brain injury in comatose children provides useful prognostic information on the likelihood of death or devastating injury. a retrospective study of children with the diagnosis of epidural hematoma was made during - period. ages ranged between days and years ( % less than year, % between and years, and % older than years), % of them were admitted at the picu. % of the cases were due to falls, % to road traffic accident and % to other causes. on admission gcs was less than in % of the cases and more than in %. diagnosis was made during first hours in % of patients and delayed more than hours in % of them. neurologic impairment was present at admission in % of patients, and delayed in %. even so, % remained without impairment. radiological findings at first ct were skull fracture ( %); epidural hematoma localization was: in the right side ( %), frontal area ( %), temporoparietal ( %) and occipital (t %). associated lesions were: several ( %) or unilateral ( %) cerebral contusions, diffuse brain oedema ( %), unilateral hemispheric oedema ( %) and % showed shifted middle line. four patients died, half of them during the first hours. fully recovered ( . %) and have sequelae of different nature : were left with severe motor disability ( %); at the follow-up t have some degree of neurodisability. next datas keep correlation with death or neurosurgical impairment: only were significative multiple cerebral contusion (p= . ) and brain oedema (p= . ), gcs less than at the admission (p-- . ), shock (p= . ) and remaining cerebral contusion in control ct correlated with death or diasability at discharge. on the other hand, neither surgical drainage volume nor first or highest levels of icp ( cases),nor pupillary abnormalities ( cases) correlated with worse prognosis. conclusion: gcs equal or less than an shock are main factors related to worse prognosis, also multiple cerebral contusions in ct and diffuse brain oedema. the results of a modified gcs were compared to outcome and intensive therapy in children (mean age , t , years) with head and associated injuries ( , % of all cases) of different causes (traffic accidents, falls). the gcs was regularly used inn the course of intensive therapy. according to our own and other experiences the gcs was divided in stages: stage ( - points), stage ( - points) und stage ( - points) palhuiugy wile sp, tdhlg c~'lcb al blood ~ w. sabgcqucntl}. rhc slat,: rerltncd to t tl, iiltlils. the p st,~pem~v~ b}i~g wij!!,:q ! ,:_a!~p!ica!j n~:. ri~;¢ ill the level of sensibflizatjou lo tile cerebn~ anhgrns up to t. -o was flofcd iu i,alicnts. there wa.~ al~ iuclt~a~e ill cerebral vdociij,. ~m d~;'ati a il~ p¢fiphc~ai re~ista/isc of the large ce~'bral ve~ds. neur h;~c ~:yn'.pt,m~at !a~, (s::mno!en~', _r_uscu!~r l~:pot ni& !ryper*'flema) was nbserwed tu lt~ese pal~enls o. cbruc~l ~ nnds. rile ple~c.ut abse~vafion~ suggesl ihal die ~tttdy at" ihe stale ~f hematocr~chcplm/itic bm~ic~ in ckil&en with on emergensy is of abviou.~ !?ece~sib; in co~.te ctin g severe pa~ lo ~-i~mnediately f u wing ne ,:~per,'~fion. background: reconstruction of the heart by three-dimensional ( d) echocardiography provided new information on anatomy of complex congenital heart defects, we assessed the utility of d ultrasound in detecting morphological changes in cerebral anatomy in newborns before and after cardiac surgery. methods: transfontanel cross-sectional ultrasound, scans were obtained in standardized coronal and median sagittal planes. subsequently, rotational scanning was used to acquire the multiple sequential crosssections of the brain. for rotational scanning, a conventional mhz transducer was rotated degrees.scanning took less than one minute and required no sedation, data was stored in the image processing computer which allowed for off-line three dimensional reconstruction of different brain regions.twelve infants aged - (median ) days were assessed before and after cardiac surgery, results: cavity of lateral ventricle, choroid plexus and the periventricular brain parenchyma could be reconstructed in all. accurate estimation of size and volume of lateral ventricle, aqueduct, and other ultrasonographic visible pathological brain lesions could be performed. reconstruction of various brain areas was accomplished in - minutes. the localisation and extension of severe periventricular hemorrhage which was detected preoperatively in one infants was better visualized than in conventional ultrasonography. epicortical and subarachnoidal space could be reconstructed in all and allowed detection of hemorrhage in one case which was not detected by conventional ultrasound. conclusion: d reconstruction of different areas of the brain may provide additional quantitative information on size and volume of the internal ventricle and choroid plexus, and better understanding of the topographical aspects and the extension of intra-and periventricular hemorrhage than conventional cross-sectional ultrasound. introduction: intracranial cerebral blood has been estimated to be % venous, the invasive measurment of venous blood saturation in the jugular bulb provides quantitative information on cerebral oxygen supply and consumption. however, routine oxymetric measurement of blood saturation in the jugular bulb by insertion of a catheter line into the internal jugtdar vein is an invasive procedure which has limited use especially in infants and young children. thus the aim of this study was to investigate the correlation between the non-invasive spectroscopic measurement of rso and the oxymetric determination of the blood saturation in the jugular bulb in infants and children undergoing routine cardiac catheterization.. methods: during routine cardiac catheterization infants and children (age day- year, median , year) the rso was measured continuously using a two chanel cerebral oxymeter (invos a). the sensor was placed in standardized location at the left temporal head side. after the routine oxymetric blood sampling in the superior vena cava the oxymetric catheter was manupilated into the left jugular bulb. after control of the catheter position simultenuous values of the rso were documented. results: over a range of ( - %) sjo , a significant linear correlation was found between the spectroscopic measurement of rso and the oxymetric determination of venous blood saturation in the jugular bulb (r= , , p< , ) and the superior vena cava (r= , , p< , ). no significant correlation was found between rso and the arterial blood saturation in the descending aorta and as well as to the standared hemodynamic parameters. conclusion: meusurement of rso by mrs may provide continuous non-invasive information on cerebral venous blood saturation and thereby possibly on cerebral oxygen supply and consumption in infants and children. these may be of clinical value particulary during and immediately after heart surgery by means of non-pulsatile cardiopulmonary bypass. information on refractory status epilepticus (rse) from developing countries is scarce. we analysed cases of rse admitted over last yrs. the objective was to study etiology end evaluate efficacy of diezepam infusion. median age of the patients was . years irange . months to t . yrs); % were boys. onset of seizures was -t hours (median hours) prior to hespitalisation. the glasgow coma scale score ranged from . (mean+sd + ). the commonest underlying causes were acute cns infections ( / , %; bacterial meningitis, , encephalitis, ) and epilepsy ( / , %). oiazepam infusion in incremental dose (range . - . mg/kg/min) was used in patients over . _+ . days. seizures were controlled n ( %), mechanical ventilation was required in ( %)only, while none had hypotension; % patients survived. thiopental infusion (holus mg/kg followed by . mglkg/min, and increments of . mg/kg/min till seizure control) was used in patients over . _+ . days; seizure were controlled in all, but five patients needed mechanical ventilation, six developed hypotension needing infusion of vasopressoi drugs, out of ( %) died, overall mortality was %, mainly due to acute cns infections (n- ) and prolonged se. the patient was a -year-old gift di~aosed of dov,~'s s~drom¢, tetralogy of fallot. (t.f.) before admission a vasovagal crisis after coughing and vomiting was seen, and she was taken to the emergency room. mother said she had eyanosis in the mucous membranes of the mouth with exercise.on physical examination, she ~as afebrile, normal fundi and neurologic examination was normal. a harsh systolic murmur was hear~ with decrased intensity during bradycardia. chest rx disclosed a decreased pulmonary vascular markings. ecg: synus rhythm, with bradycardia and nodal escape rhyflmas. she was transferred to our picu because of severe h ,pertomc seizure, lost conciousness, and deeembrate poslamng~ ~t cyancx~is. the episode lasted for ~weral seconds, and ceased v~th diazepam. on admission she was lethargy, and neurologlc exammation showed weakness of left leg without babinski, and normal funduscopic. the patient had two episodes of bradycardia and isoproterenol was begun. during those episodes the patient was cyanotic, and the murmur was heard with the same intensity. act scan disclosed a tight parieto-temporai abscess with midline shift, lnmediately after the diagnostic ct, we administered antibiotics, antiedema treatment and it was drained. the abscess culture was negative. a ct control disclosed air and midlme shift. ~ the next two days she had three episodes of h oxia and c'yauosis ceased with o@gen, morphine and propanolol the patient died during a fourth episode. discussion: arrhytmias are uncommon in patients with tetralogy of fallot before surgery. in our case the first diagnosis was sick sinus syndrome vs bradycardia secondary to cyanotic episodes. the incidence of cerebral abscess in children with congenital heart disease (chd) is approximately %. tetralogy of fallot is the most common associated lesion, and is unusual in children under years of age. conclusion: ) brain abscess is a rare complication of patients with cyanotic chd, but should be suggested in patients with °'apparent" sick sinus syndrome. in patients with down's syndrome, t.f.,with cyanotic episodes, and difficult neurologic exploration, a brain ct scan is recommended. guillain-ba~re syndrome (gbs) is an acute autoimmune reaction, directed primarily toward the myelin encasing the peripheral motor nerves= this reaction causes a delay or block in nerve conduction. the presentation often can be very subtle but is followed by rapid loss of neuromuscular power, leading to acute respiratory distress, resulting from weakness of muscles and aspiration pneumonia. there were boys - , , and i i years old with gbs, treated in our icu. two of them due to the respiratory distress were intubated nasotracheally and ventilated mechanically with servo- ooc (siemens-elema, sweden) ventilator. duration of ventilation was i i and days, respectively. plasma exchange was performed in all cases. the numbers of plasma exchange sessions were - in each case. mean amount of plasma exchanged per session was , ml/kg. plasma was substituted with albumin, plasma or saline. the most important aspect of the management of patients with gbs in the icu involves the airway care, prevention and treatment of aspiration pneumonia and the mechanical ventilation if respiratory distress presents. endotracheal intubation should be performed whenever there is evidence of retention of pulmonary secretions, refractory to chest physical therapy, weakness of protective reflexes of the airway, leading to aspiration pneumonia and (or) atelecr~sis. cardiac arrhithmias too, is a main threat to the circulatory stability in gbs. therapeutic plasmapharesis has been shown to be beneficial, reducing the time for weaning from the ventilator and for achieving independent ambulation. however, plasma exchange is expensive and not without significant risks for the patient. some authors find that plasmapheresis is not effective for patients with fulminant course of gbs and blocking of nerve conduction. recent studies have demonstrated that intravenous high-dose immunoglobulin can be equally effective. there were no significant complications associated with plasma exchange. all presented patients survived without residual disability. tetraparesis associated with long-term paneuronium use in an infant. paneuronium is a muscle relaxant used in ventilatory management of patients with respiratory distress in intensive care unit. after the end of sedation some patients were found to have severe tetraparesis. paresis was accompanied by complete areflexia and diffuse atrophy of alt extremity muscles. this neuromuscular complication is caused by prolonged high-dosage pancuronium treatment. in the last years, numerous reports have linked the use of pancuronium bromide with prolonged paralysis, disuse atrophy and areflexia. this side-effect is well known in adults patients but rare in a pediatric intensive care unit. we describe one pediatric observation of tetraparesis after prolonged pancuronium treatment in a -month-old girl, this female infant developed respiratory distress syndrome and was intubated and mechanically ventilated. to decrease chest wall rigidity pancuronium bromide was administered during days. (she received approximately mg of pancuronium bromide). on day the drug was discontinued and the patient had severe tetraplegia and areflexia with normal head movements. electromyograpliy showed absence of any disorder of neuromuscular transmission. this infant showed a recovely of muscles after months. the other causes of peripheral neuropathies were eliminated. electroencephalograms and head scans were normal. the recovery pattern observed in our patient correspond to the process of regeneration after axonal degeneration. it is suggested that these neuromuscular complications were caused by prolonged high-dosage pancuronium treatment (associated with cortieoid and aminoglucosides). polyneuropathy syndrome in adult lc.u. appeared in literature in and is extremely common in long stay cases. the etiology of these disorders remains elusive. it is tempting to ascribe them to administration of drugs (muscle relaxants, steroids, aminoglycosidea), plolonged immobility, malutrition, sepsis and ischemia associated with reperfusion injury. to our knowledge there is only one case report of similar condition in a children i.c.u. (pascucci ) we present a serie of previously healthy children, aged months to years, who admitted in i.c.u with respiratory failure and who following weaning from m.v, remained in profound diffuse hypotonia with proximal and distal muscle weakness for various length of time, recovery of muscle strength occured in a week or months {the longest i months), all children, except one, - days before admission developed symptoms of either respiratory or upper airway infection with fever. on admission viral and bacterial cultures were positive in cases (haemophilus influenze, herpes virus). during treatment patients became septic. muscle histological and neurophusiological investigations have not been done. considering the multifactorial nature of the aquired nmd in adult critically ill pts, is impossible to attribute the muscle weakness of our pts to any specific cause, in conclusion, our findings suggest the need for further investigation of nmd in critically ill children treated in i.c.u. a van esch, ha van steen~l-m , ir ramtal, g derksen-lubsen, idf habbema. febrile status epilepticus (fse) is a prolonged and serious febrile seizure. little is known about the outcome of fse in neurologically normal children. this survey involved patients between months and years of age who had visited due to their first fse, the sophia children's hospital during the period of january till december . patients with a history of neurologic disorders were excluded. patients were identified, % were male. the cause of the fever remained unknown in % of the cases. in all case the fse was generalized and it most frequently occurred at night ( %). the mean age at fse was t. years ( . - . ), the mean temperature . °c ( . - °c). the mean follow up time was . year. twelve children ( %) had neurologic sequelea. the neurologic sequelae varied from speech deficit ( case mild, v - year delayed; case moderate > year delayed) to severe retardation and epilepsy ( cases). speech deficit was detected after a mean period of months (range - ), age, gender, temperature, family history and time of onset were no significant risk factors for neurologic sequelae. duration of seizure [rr . ( . - . )] and more than two drugs to treat fse (rr . (t. - . ) were related to neurologic sequelae. we recommend that fse children should be followed for at least a year to detect possible speech disorders properly and start early intervention. unusual presentation of myasthenlg gra%qs ibtza e. modesto ,v~ abe~gochea a, sanch]s l all, go l varas k folgado s, garcia e. p. .c.u. la fe, valencia. spain case report: the patient was a -year-o!d gift transferred to our pic because of severe respiratory failure. the patient, convaleseem of ehiekenpox, came into contact with horse manure previous afternoon. in the morning, she was lethargy, and irritability, with poor finding, and ~ an episode of coughing, cyanosis and acute respiratory failure after mucous vomiting when she was drinking milk. on admission she had severe respiratory distress, respiratory acidosis, and the sat was %. she was mtubated without difficulty, and was transferred to our p.i.c.u. physical examination reveals stable hemodynamies, pupils equal, round, reactive to light, normal fandi, and muscle relaxation. crusted vesicles diseminats~d. rhonehi over both lungs. hepatomegaly (+) and splenomegaly (+). ~lhe urine, hematologic, and c.s.f. laboratory findings were normal. c.t. scan of the brain, e.e.g., and ekg. revealed no'abnormalities. rx chest disclosed a retrocardiac atelectasis. speci~ts of stool and blood were obtained for cultures and study of c. botul#num toxins. pending receipt of these results, a broad-speotmm antibiotic and acyctovir was begun. the initial differennal diagnosis consisted of laryngospasm associated with aspiraqlon, botulism, and postmfecfious varicella encephalitis. after hours, weatm~ was begun. the neurologic examination showed a low modified glasgow coma ~ale (mgcs), generalized hypotouia and muscle weakness. these data suggested three diagnoses, posfnfecfious encephalitis, residual neuroumsoaar blockade, and excessive doses of sedative and analgesic drugs. after hours she regained skeletal muscle poxver and ufltlcient respiratory effort, the mcgs was acceptable, and blood gases were normal. she was given n~-tigmine and atropine, and her tr~ma was extubated. an acute respiratory failure ocurrs ram. after. chest radioga'aph disclosed a left inferior lobe atelectasis. after hours weaning begun~and the same episode w~as seen. at this point her mother stated that the girl showed weakness of the eyelids or extraneular muscles. it suggested myasthenic syndrome vs ~-barr syndrome. c. botul#num toxins were negative, chotinesterase level ~as normal. edrofoinum test ~as positive. anti-acetyleholine receptor antibodies were negatives. e.m.g. confirmed myasthenia gravis (congenital vs juvenile serenegative). pyridostigmine was begun and the trachea was extubated without complications. conclusion: din the differential diagnosis of weamng failure we must consider ~c gravis~ )myasthenia gravis could resemble encephalitis, because of low ocs, overall if is triggered by viral infection. )in some diseases (this case) gcs could not he an aemuate index of mental state. a burguet*, a menget*, e monnet**, a gasca-avanzi*, c fromentin*, h allemand**, jy pauchard*, ml dalphin*. * r animation infantile potyvaiente chu st jacques besancon cedex. ** d~padement de sant publique besancon cedex, france, objective : to point out that strabism is) of one-year-old premature is a good predictor of a poor neurological outcome at two years of age. design and setting : two-year prospective cohort study and geographically defined study (region of franche-comte, france). main outcome measures : neurological assessment was performed at one and two years of age (uncorrected for gestationnal age). a mailing questionnaire was sent to the famity and fuu-filled by thefamily doctor (pediatrician or physician), or neonatologist of the icu at tertiary center, s was diagnosed at one year of age by the examinator but s was not used to diagnose cerebral palsy (cp). sample : of survivors ( %) evaluated at one and two years of age. results : correlation of one and two years neurological evaluation is weak (kappa= . ). correlation of s at one year and cp at two year is fair (kappa= , ). the goal of this paper is to review evidence related to hypothesis that the "waiting" axons and cells of the transient subplate zone may participate in the structural plasticity of the human cerebral cortex after perinatai brain damage (kostovic et al, metabot brain res : , t ) and to correlate this phenomenon with different forms and mechanisms of structural plasticity. it is our basic assumption that all lesions occuring during cortical histogenesis will lead to more or less pronounced structural reorganization. here we show that various components of the subplate zone participate in several forms of the structural "plastic" responses in the human cortex: modification of convolutional pattern, changes in size of cytoarchitecturat areas~ columnar reorganization, dendritic and synaptic plasticity. the etiological factors which induce lesions and subsequent plastic changes act via the following pathogenetic mechanisms: * disturbances of radial unit formation (rakic); * changes in ingrowth of afferent fibres; * changes in the rate of normally occuring reorganisational events, depending on the critical period for a given histogenetic event. in the present study developmental lesions (localized perlventricular leukomalacia and haemorrhages) were demonstrated by ultrasound in live-born infants ranging between to weeks of gestation. in younger infants ( - w) who died shortly after birth, examination revealed lesions of the white matter with the preservation of the subplate zone. in infants who died one week of more after the lesion, we have observed localized micropolygyria, cavities, condensed layer vi -subplate zone, and columnations of the cortical plate. these changes are less prominent if the lesion occurs after diminishment of the subplate zone (after w). since in the fetal cortex the subplate zone serves as predominant source of growing fibers, transient neurons, trophic factors and contains cellular substrata for migration, this zone is the most likely candidate for major types of structural plasticity. in conclusion, cerebral cortex of the low -birthweight infants is more susceptible to the various lesions but shows vigorous structural plasticity and conspicuous functional recovery due to the growing, transiently located neuron at elements. the mortality due to meningoccocal sepsis is high in spite of important progress in emergency and intensive care medicine. during the last decade multiple scoring-systems have been developed in order to establish a therapeutic approach and to evaluate the final outcome of a meningococcal infection. different clinical and biological data (shock, ecchymosis, peripheral wbc and platelet count, coagulopathy, acidosis, meningism, etc) are taken into consideration and the importance given to these data depends on the scoring-system used. a review of the different scoring-systems is given and a clinical case is presented. we report the case of a year old male, who was transfered to our icu hours after onset of temperature and skin rash. the parents described a fast deterioration of his condition. the boy presented wide spread ecchymosis, high temperature, no signs of meningism, circulatory insufficiency and shock, coagulopathy and low peripheral wbc and platetet count. disseminated intravascular coagulopathy developed promptly. the glasgow meningococcal septicemia prognostic score (gmss) was used and the obtained score reached the highest level ( / ). this corresponds to a % mortality. the patient required mechanical ventilation for days. at admission he received human albumine, fresh frozen plasma, dexamethason, dopamine, dobutamine and a continuous infusion of adrenaline. antibiotical treatment consisted of ceftdaxone. the evolution was favorable and the infant fully recovered. retrospectively the gmss was compared to other meningococcal scoring scales which gave the same mortality ( %). we conclude that the scoring-systems are important to evaluate the seriousness and to assess the therapeutic approach, but they should be used cautiously even when % mortality is predicted by several risk evaluations scoring-systems. the aim of this study was to assess the haemodynamic status on admission and the critical care management of children presenting with meningococcat infection. this was a retrospective study of the charts of consecutive admissions. mean age was . years (+/- . ). the average duration of symptoms prior to admission was . hours (+/- . ). on admission . % were hypotensive, . % had clinical signs of haemodynamic instability and . % of cases that had a blood gas analysis on admission had a metabolic acidosis (bases excess < - .q): the mortality rate was . %. % of patients that died were hypotensive on admission and all had a metabolic acidosis. of the survivors . % were hypotensive on admission, % had clinical signs of haemodynamic instability, % required invasive pressure monitoring and . % were ventilated and received inotropic support. this study demonstrates that at the time of presentation with meningococcal infection children had a high incidence of established haemodynamic instability. successful management of this infection is dependent on early presentation and initiation of therapy and on aggressive support of the cardiovascular and vital organ systems. dept. of intensive care medicine and dept of infectious diseases, our lady's hospital for sick children, crumlin, dublinl , ireland. jude. pediatric intensive care unit, ch&u, lille-france. more than % of children surviving sip (defined as purpura with shock) have snli. objective. to search for a specific hemostatic profile in children with snli. patients and methods. between may and march , children with sip were admitted to our picu : ( . %) died and ( . %) ranged in age from to months (mean : ) survived, of them ( . %) with snli (defined as the need of a surgical procedure). in survivors, two hemostasis studies (between h and h , and h later) included the determination of coagulation factors (routine tests), protein c (pc : amidolytic activity, biogenic), total protein s (ps : elisa, stago), c b binding protein (c bbp : laurell's technique, stago), antithrombin (at : chomogenic test, stago), and plasminogen activator inhibitorl (pail : chromogenic test, biopool). three severity scores were determined at admission : french group of pediatric intensive care, gedde-dahl, and crp. statistical analysis used the wilcoxon's test. results. at admission (lst sample) severity scores and at , pc, ps, c bbp levels were not different between the group with snli and the group without snli ; quick time ( - % vs ± % ; p = . ), vti+x ( . % vs - % ; p = . i) and pall ( - ui/m! vs . ui/ml ; p = . ) were lower in the group with snli. on the nd sample there was no difference between the two groups. kinetics of hemostatic abnormalities was not different between the two groups. conclusion. in the literature, intravascular coagulation (dic), low fibronectin and at were identified as predictors of snli, and a negative correlation was found between the mean size of the skin lesions and pc activity, at , and total ps. in this series, apart from dic, there were no specific hemostatic abnormalities that support the use of treatments such as pc, at , and pail antibodies administration to prevent snli. further studies including more children are needed. the aim of study was to investigate the efficacy of intravenous immunglobulin with enriched igm content pentaglob/n /biotest/. in our pediatric intensive care unit ten septic children /group i/-their average age , years /sd:o, /, of them with gramm negative and one with gramm positive blood cultures, and two with unindentified bacteria-were treated with basis sepsis therapy and pentaglobin. the application of pentaglobin was as follows: , ml/kg loading dose for one hour, followed by a continuous intravenous infusion , - , ml/kg/hour depending on body temperatura /lanser scheme/ for - hours. another ten septic patients /control-group ii/the mean age , years/sd:o, /, their blood cultures were gramm negative bacteria , positive , and the bacteria was not indentified in two cases -were treated with only the basis therapy. results: the duration of intensive treatment decreased from an average , days /sd: , min -max days/ to , days /sd: , min -max days/ in the group treated wit pentaglobin. the difference was significant /x p< , /. in the group i nobody died, but three in the group ii. conclusion: the pentaglobin therapy can improve the efficacy of the basis therapy of sepsis. sinus bradycardia after an episode of sepsis is a rare symptom complex decribed in children with hematologic malignancies. we present a case of postsepsis bradycardia following severe typhlitis and septic shock in a year old boy with relapse common all. blood and ascitic fluid specimen grew clostridium species and pseudomonas aeruginosa. at surgery there was a necrotic gangrenous terminal ileum and cecum, requiring ileocecal bowel resection with ileostoma. while clinically recovering from sepsis he developed bradycardia for hours. extensive diagnositic procedures was given and the heart rate slowly increased to normal range of age. postsepsis bradycardia in children with hematologic malignancies after an episode of sepsis is self-limiting and after careful differential diagnostics warrants an expectative attitude. nitrate level is known to be enhanced during sepsis. serum nitrate is the stable metabolic end-product of endogenous nitric oxide generation. nitric oxide has demonstrated to be a powerful anti microbial final mediator and also a key molecule driving to the lethality of one of the most common complication of sepsis; the endotoxic shock. such facts prompted us to investigate the possible diagnostic and/or prognostic value of monitoring serum level in high risk, presumptive and confirmed sepsis patients. additionally we have explored the usefulness of this mediator as index of therapeutic response. in our study it is demonstrated that there is an important relationship between nitrate level and the occurrence of neonatal sepsis. septic newborn group showed fold higher nitrate level than that of healthy control group. in addition, the group of patients with high risk of sepsis which finally became septics, exhibited fold higher nitrate level at - hours before the first symptoms appeared, when compare with those who did not develop sepsis. however in the presumptive sepsis group, there was no difference between the patients which finaliy ,&'ere considered septics and those which not. in all septic cases, after days of a successful therapy with antibiotics, the level of nitrate diminish fold. our results suggest the utility of monitoring nitrate as index for the diagnosis of neonatal sepsis. the potential benefits of exchange transfusion, plasma exchange, and haemofiltration have all been described in children with overwhelming sepsis. however, little hard evidence exists to prove the benefits of any of these techniques. i have treated five patients with plasma exchange (pe), having been asked to see all these patients at a point when it was felt death was inevitable. two of the patients had staphylococcal, two meningococcal and one enterococcal septicaemia. all patients showed a dramatic haemodynamic improvement following pe with improvement in blood pressure, reduction in inotrope requirement and improvement in tissue perfusion. three patients survived. one of the patients with staphylococcal sepsis and both of the patients with meningococeal sepsis had developing gangrene of the limbs which showed remarkable reperfusion with pe. in two of the patients measurements of cardiac output (co) and systemic vascular resistance (svr) showed ~a reduction in co and a rise in svr over the course of a pe despite the reduction or cessation of vasoconstricting inotropes. many believe haemofiltration is of value in septic shock. a trial with a no treatment limb is difficult to achieve. i believe we now have enough evidence to justify a controlled trial of haemofiltration versus plasma exchange in patients with septic shock and unstable haemodynamic status whilst on inotropic support. during the next several days, cough and chest pain suggested pulmonary embolism confirmed by radiologic evaluation. echocardiographic examination showed multiple thrombosis of the superior vena cava, right atrium and ventricle and pulmonary artery. estimated protein c level was . % (normal range - %); identical deficiency was found in patient's mother and elder sister. cvc was removed, and alter -month heparin therapy and supstitution of protein c with fresh frozen plasma, there was almost complete thrombolysis of the great vessels and cardiac chambers. we conclude that invasive diagnostic and therapeutic procedures in such patients may result in higher risk for severe thrombosis at unusual sites, and numeuos further complications bronchopulmonary dysptasia (bdp) is a chronic pulmonary disease of preterm and term babies treated with mechanical ventilation for respiratory problems of different origin and requiring oxygen therapy days after birth. bpd is a disease affecting the growth and development of pulmonary tissue. such pulmonary }esions heal by squamous metaplasia leading to scar formation and fibrous tkssue r~growth, the pediatric intensive care unit makes the survival of babies w~h very low birth weight ( - g) possible. with the increase in their aulyival, the number of complications in low birth weight babies increases as well. bdp is a very serious complication. therefore the importance of early diagnosis and treatment of bdp must be stressed in order to reduce the consequences. babies with bdp must be under medical suveillance for at least years as the disease needs at least that long for complete resolution. tn the icu of pediatric department at madbor teaching hospital: during the past two years ( - ) newborns were treated with mechanical ventilation. the neonatal and postnatal death rate of all newborns admitted to our icu was , %o.ln the two years from to , newborns were admitted to our icu ( %~ of all newborn babies at maribor teaching hospital), with birth weight - g. in the icu, the survival of these babies and parallel to it the number of complications is increasing. during the mentioned -year period, babies with very low birth weight ( - g) survived: in and in t . in - %, first or second stage bdp was treated,there was no case of third of fourth stage bdp. the treatment consisted of eary removal from mechanical ventilation, oxygen therapy~ intensive treatment of infection, volume and caloric intake contro}, corticosteroid treatment throught weeks with decreasing doses, diuretic end antioxydant therapy. the children are to be reevaluated at the age of and months and again at i and years. oeure j van der, markhorst do, haasnoot k department of pediatrics, pediatric intensive care unit, free university hospital, amsterdam, the netherlands. case summary a %-month . kg girl of african origin was admitted to the pedfatric irtensive care unit with pneumonia and progressive respiratory irlsuffjderey. she was intubated and ventilated by pressure regulated volume controijed ventilation (servo c, siemens, soma, sweden). maximum conditions were inspiratory minute volume . l, peep cm h~o ahd % ~. chest x-ray showed bilateral interstitial consolidation. material obtained by broncho-alveolar lavage showed preumocystis car}nil htv-serology (elisa and westerll blott) and p -antigerl were positive, confirming the diagnosis of pediatric aids. she was then treated with high dose co-tllmoxazoie, penthamldine, z{(~ovudire and steroids iv. because of thee x-ray features, high need for o ( %, pad mm hg), not responding to elevatiofi of peep (max cm h=o) and pao /fio = < (s ). m acute respiratory distress syhdrome (ards) was diagnosed. because conventional ventilation (cv) failure, hfo-v ( ooa, serisor medics,yorba linda, ca) was initiated. starting mean airway pressure (map) of cm h~o was based or map of the cv, oscillatory pressure amplitude (dp) of was, at ii~itial frequency of . hz, adjusted ur~til chest wall vibrations were visible, it was required to raise map to cm h and dp to before optimal lung volume and ventilation were achieved and need for o reduced within hours, this was monitored by frequent blood-gas analysis and chest x-rays. map and dp could slowly be reduced, after a good response the first day, gradually demand reduced and the patient could be weaned from the ventilation. map, dp, fi and oxygenation index (map x pa ~jfio ) are shown in table i. chest x-ray follow-up showed gradually improving lung features, with marked improvement of aereation. after days hf -v she could be succesfully detubated when a map of cm h was acmeved. results : sianificant increase in ventilato~ rate and mean airway pressure was noticed after the change to savi. no differences in oxygenation, co partial pressure and systolic, diastolic or mean blood pressure between imv and savi periods were noted. in infants however an improvement in pao /p .ol/ and decrease in paco was observed after the switch to savi. these babies had a lower initial a/a oxygen tension ratio and required higher initial ventilator rate /p<o. / in comparison to the rest of the studied patients. conclusion:infants with low a/a po ratio who need high initial ventilator rate are likely to obtain benefit from savi.. fumimare hatori, haruo uchida, masao katayama, and rika muto department of anesthesia and critical care medicine chiba children's hospital, chiba city, japan. purpose: this study was made to find out whether the heat and moisture exchangers (hme) was effective enough to humidify in the respiratory management for children. patients: the study population consisted of patients who were provided with artificial airway. they were divided into the two groups: ii with heated humidifier (a) and i with hme (b). methods: hme could be used for those without pulmonary complication and with less leakage around the endotracheal tube. in both a and b groups, (i) we have measured relative humidity, temperature, and absolute humidity at the endotracheal tube connector. for these measurements, humidity sensor system was utilized. ( ) any troubles and complications caused by the artificial airway were investigated. results: (i) in group a, we confirmed the mean values as the relative humidity of . %, the temperature of . ~c, and the absolute humidity of . mg/l. in group b, they were . %, . °c, and . mg/l respectively. no difference was noted between the two groups as to the relative humidity, but the temperature and absolute humidity were lower in group b with a significant difference (p< . ). ( ) in neither of the groups, any respiratory complications such as obstruction or stenosis of the artificial airway were noted. in pediatric icu, hme can be used without any problems under given conditions. titei: objective: evaluate the precision, reproductibility and aplicability of a new device to measure auto-peep in pediatric patients during mechanical ventilation. material and methods: it's an electromc-pneumatic eontolled device with an oclusion valve and a pressure monitor installed between endotracheal canulla and the ventilator circuit. the measurements were performed with a sollenoid conected with to the ventilator to detect the end of inspiration phase and the actwation of the oclusion valve. the signs of pressure and flow were moniturized using a difere~rtial transducer and it was processed using a pc computer and a pneumoviaw® software. the auto-peep also displayed in the ventilator pressure monitor. results: we submitted children with neuromuscular disease or respiratory distress in this study. the incidence of auto-peep was %, with variability between , to cmh . all the measurements were performed times to verify the precision and the reproduetibility and evaluation of the pressure and flow curves. conclusion: the device is low cost, easy to use and can be used without the pneumotacograph. the auto-peep measurement can be done during mechanical ventilation with time cycled, pressure limited and continuous flow, the most commom ventilator used in pediatric patient. resistance was modeled by endotracheal tube (ett) sizes ( . , , , ), and compliance by test lungs ( and ml/crnh ), for each resistance -compliance arrangement, we measured tidal volume (vt) at various frequencies, peak to peak (p-p) and mean airway pressures. results vt increased when ett size increased with all ventilators in accordance with fredberg results (jap, ; : - ) . the maximum vt delivered was smaller with the hfv-babyiog than with the ohf or the sm a at a given frequency (figure on the left). increasing p-p resulted in a linear increase in vt delivery in the - % range of maximum p-p (figure on the right). hfv-babylog didn't provide significant vt increase when p-p was set above % and vt deliven/decreased when mean airway pressure decreased. --i ~ sm a a number of ventilatory parameters had been analyzed with russia-produced monitor humitemp htm (servisinstrument j,-s. co) in newborn infants with rdsn of t-iv stages on cmv, cppv, imv, and cpap steps using respirators of various kinds (stephan-staxel, bear- , newport rezee, sechrist). parameters investigated were: temperature of inspired mixture (t), relative and absolute humidity (rh and ah, respectively), static compliance (c), expired tidital volume (vte), expired minute volume of ventilation (mve). the monitor read these parameters in following ranges; rh-from to %; ah-up to mg/i; mve-up to . i/mini vte-from to ml; t-accurate to %; c-from . to t ml/cm h . continuous monitoring time ranged from to hours, it was noted, that during this time the monitor and transducers had no malfunctions, and it's using didn't require additional calibration, it was found, that humidifiers mr and mr (fisher, paykel) couldn't maintain parameters t and ah continuously (these values varied from , to . c and from , to . mg/i, respectively, when heating regulator position was unchanged). changes of parameters c depended clearly on cppv conditions and rdsn severity (with rdsn of stages i-ii c value ranged from . to . ml/cm h ; and with stages iit-tv-from . to . ). tn newborn suffering from rdsn of stages ii-ltl and ill-lv with pip> mbar, fi > , , peep= - mber, c-from . to . ml/cm h , effectivity of exosurf therapy was studied. in newborns in - hours of therapy pip decreased to . - . , and c increased to , - . ml/cm h . in newborn infants with aad > mmhg and c from , to . mltcm h positive effects of exosurf on lung compliance were not observed. in newborns the monitor had revealed decreased of c (from . - . to , - . ml/cm h ), manifested clinically by pneumothorax. in general, monitor htm made possible; ), to estimate the adequacy of cmv-parameters and regimes in newborn infants; ). to select optimal t and ah values in the respiratory outline in dependence on lung damage severity and infused volume; ). to reveal rdsn severity; ), to optimize indications and adequacy of surfactaot therapy; ). to diagnostieate the air leakage syndrome; ). to effects to some agents (broncholytics, spasmolytics); ). to obtain objective indications for imv/simv and cpap regimes. albano communication is an important aspect of human development and existence, and an inability to vocalise can be a problem in ventilatordependent patients. we present our experience with speaking aids as a means of enhancing verbal communication in four ventilatordependent children in our paediatric intensive care unit. the age of the children ranged from months to years, and the period of ventilation ranged from months to months via a tracheostnmy. they require continuous flow generated pressure limited or control ventilation at rates of - bpm. the reasons for ventilation include tetraptegia following a shrapnel injury; tetraplegia following congenital cervical spine damage; tetraplegia following atlanto-axial subluxation; and critical illness polyneuropathy following adult respiratory distress syndrome from prolonged ventilation for a severe head injury. the first three patients have passy-mnir one-way speaking valves and the final patient has a bivona foam cuffed tmcheostomy tube with a talk attachment in view of recurrent aspiration. an improvement in quaiity of speech has been shown by independent assessment. we will review the present literature on this subject and discuss the advantages and disadvantages of these two types of speaking aids in the light of our experience. the prognosis of antenatally diagnosed cdh is closely related to the degree of ph. there have been attempts to correlate antenatal or postnatal criteria to mortality: none have been demonstrated to be predictive of lethal ph. the aim of this retrospective study was to determine whether antenatal or early postnatal data could correlate with the findings of post-mortem examinations. patients and methods: between july and july , cdh patients have been antenatally and postnatally managed at our institution. twentythree infants underwent a post-mortem examination. ph was assessed by using the lung weight to body weight ratio (lw/bw) and the radial alveolar count (rac). antenatal results: cdh diagnosis was made at weeks of gestation (wg) ( - ). twenty-eight patients had a left sided cdh, had a right sided cdh, and one had a bilateral cdh. herniated organs were stomach none (n= ), or liver alone (n= ), or both stomach and liver (n= the patient was a -yenr-old girl with chronic renal insufficiency see~ to renal dysptasm, two months before admission a kidney trar~ptant was performed. one morah later she showed acute graft rejection with serum ereafinine (cr) level of . mg%. the rejection was unreslxmsive to an increased steroid dosage, and okt was begun with resolution of the rejection. one week arer, new rejection episode was seen marestxmsive to an increased steroid dosage, and transp~ ~s performed five days before admission to our ptc. hemedialysis and peritoneal dialysis (p.d.) each other day, was indicated (g.r.f.< ml/rnin). four days before admission t ~ rose to °c. "lhe diagnosis of opporttmistic pneumoma was made on the basis of tach ,pr',e~ hypoxi~ and diffuse interstitial infiltrates. senma ~ was positive for cytomegaloviras (cmv), and stool culture for c albicans. pentamidine, ganciclovir (dhpg), arai-cmv gamma globulin, eritromicine and amphotericin b was administered. on admission in our picu, trachea was mmbated, (a-a) o gradient was , paofffio~: , lung injury score > with peep level of cm hzo. she had normal fiver function. during te next days she had fever and developed ards. bal was negative. p.d. was of little efficiency. we adjusted pentanfdine, and dhpg doses for severe renal failure, with supplements after hero, sis, and at~rp.d.. during ~ next days she was afebrile, and the chest became radiologlcally normal. after ten days on menhani~al ventilation (mv.), the patient was extubated. cr. level was . rag%, (a-a) oz gradient was , and paoyfioz was , the patiem was discharged with chronic ambulatory p.d. discussion: opportunistic pneumonia is a major complicalaou in imm~romised children, specially after kidney tvansplaraafion. c m.v. infection can result at~r okt administration. in the treatment dhik} dose must be adapted to the degree of renal insu~cieney, with supplements after hemedialysis, and after pd. pneu~y~tis cann# tmeumov~ is ehemeterized by ventilafion-perfusion mistmaeh, decreased pulmonary compliance, hypoxia arld elevated (a-a) oz gradient, with diffuse interstitial infiltrates. in our ease bal was negative. although we did not find the etiology the prevoclons eombh~ation of arairmcrobiat therapy, along with m.v., and supportive measures were the most effective trealme~. conclusion: ) in patients with severe renal failure and life-threatening infections, we must co~ider drug adjuslments. ) in our patient we gave dhpg supplements at~r pd. with excett~at results, although p.d. was of little effiele~. introduction: endotracheal intubation and mechanical ventilation have become an important treatmem for many diseases accompanied by respiratory failure. with the frequent use of this treatment modality, an increasing number of complications associated with endotracheal intubation have gained clinical significance. material and methods: a transversal study was realized to find the prevalence of pulmonary aspiration with endotracheat tubes in infants and children. aspiration was assessed by applying two dyes (evans blue, er)¢rosine sodic) on the tongue and searching for the dye during suctioning in the endotracheal aspirate. the factors, that potentially have influenced the aspiration, including weight, age, sex, cause of respiratory failure, main pressure airway (map), level of consciousness, presence of swallowing and body position were evaluated. all the variables studied had their association with aspiration tested by chi-square method with relative risk considering a confidence interval of %. the results were adjusted by multivariate analysis. results: the overall prevalence of aspiration was . %. among all children who aspirated, compared to those who did not, there was a statistically significant difference in the presence of swallowing (p= . ). the odds ratio to aspiration in the presence of swallowing was . (t. - c.i. %) and the relative risk . . aspiration was not significantly affected by sex, weight, age, cause of respiratory failure, map, level of consciousness and position of the body during the ventilation. conclusion: the endotracheal intubated children frequently aspirate as intubated adults and that preventive measures are ineffective. the presence of swallowing movements is the main risk factor to aspiration of oropharingeal content in intubated patients. clinical features and shortterm outcome skling, rp gie pneumonia is the second most important cause of death in young south african children. the clinical features, intensive care course and outcome of children being ventilated for pneumonia in the developing world is unreported. aim: to describe the clinical findings, aetiology and shortterm outcome of children younger than months with pneumonia requiring ventilation. the data of all babies under the age of six months with a lower respiratory tract infection admitted to the paediatric icu for ventilation were prospectively collected over a period of months. tracheal aspirates and blood specimens were submitted for viral and bacterial cultures. results: forty-seven babies aged to days were ventilated for pneumonia. twenty-six infants had been born prematurely; t had been ventilated during the neonatal period and had bpd. the median duration of symptoms was day, the most common being cough, tachypnoea, apnoea and cyanosis. five babies ( %) died. the mean duration of ventilation was days (range - days) and of ward stay after icu discharge days (range - days), blood euttures were positive in children ( %). viruses were cultured in children ( %). conclusion: ) fifty-five percent of children below months requiring ventilation for pneumonia were premature infants, of whom % had been ventilated during the neonatal period. ) the median duration of symptoms prior to admission was day. ) ninety percent of the children survived and were discharged from hospital. ) viral pneumonia was responsible for % of the admissions. mechanical ventilation and atrial natriuretic factor release ulloa santamarfa, e, p rez navero jl, ibarra de la rosa i, espino hernladez m, velasco jabalquinto mj, frfas p rez m. picu. reina sofia children's llospital. c rdoba. spain. mechanical ventilation effects on renal function decreased diuresis and natriuresis due several factors including anf. several studies have demostrated anf released due increaasing pressure in right atrium. on the other hand, mechanical ventilation, overall peep modality, inhibits peptide release althougt cvp increased is found. this study was designed to demostrate anf stimulation is due rigth atrium stretch which be higher during mechanical ventilation instead of atrium pressure. we desing a prospective study including patients, age range months- years with congenital heart disease. all of them were admitted at pediatric intensive care unit after extracorporeal surgery and were assisted by mechanical ventilation. hemodinamic state was stabilized in all patients and nor renal neither neurological diseases were found. after hours with mechanical ventilation, plasmatic levels of anf were measurement, pvc, pericardical pressure were assessment; all patient were sedated with midazolan and paralized with neuromuscular blocking agent; mechanical ventilation technique was as follow: imv between and , tidal volume and fi o enough to mantain respiratory parameters in normal range. afterwards, at least twentyfour hours in spontaneous breathing, the study was made again in each patient. atrial stretch was assesssment according to following equation: transmural pressure= cvp -pericardial pressure. cvp were significantly higher with mechanical ventilation than when the patient was breathing by himself. ( . +__ . vs . + . mm hg; p< . ). however, transmural pressure during mechanical ventilation were lower than during spontaneous breathing ( . +__ . vs . +__ . mm hg; p < . ) equal, plasmatic anf levels were lower during mechanical ventilation ( . + . vs . + . pg/rnl; p< . ). in conclusion, anf secretion decreases during mechanical ventilation, even with cvp higher. anf release would depend on atrial stretch meassured by transmural pressure, lower in patients with mechanical ventilation and it would not depend on atrial pressure. the paediatric intensive care unit shaikh zayed hospital, lahore is an acute care area devoted to the care of critically sick children upto the age of years. in a bedded unit with limited equipment, constant care is ensured by the presence of at least one nurse aed one doctor round the clock. in this setup we have the facility to ventilate - children at one time, between sep. and dec. , out of patients admitted to icu, ( . %) were below yr of age, while ( %) were below month of age. life support was discontinued in ( . %). total mortality was ( . %), major mortality was in - month age group ( . %), and month to month ( . %). majority of the patients were of sepsis ( . %), cns disorder ( , %) followed by respiratory problems ( . %). it seems therefore that the major indicatiou for ventilation was overwhelming septicemia leading to multiple organ failure, rather than purely respiratory problems. high frequency oscillation (hfo) in the therapy for ards in pediatric patients requiring aggressive conventional mechanical ventilation (cmv) -routine or experimental mode ef pre ecmo therapy. fedora m., nekvasi~ r, vobruba v., srnsky p,, zapadlo m. dpt. critical care medicine, nicu and ecmo center, university children's hospita! brne, nicu of university hospital prague, czech republic. introduction: pediatric patients ( males, female, average age . months, average body weight , kg) with severe ards ventilated with aggressive regimen of pcv or prvc were connected to hfo (sensormedics ) as the last "rescue" therapy due to uncontrollable respiratory failure before intended ecmo. in the course of hfo of them were given no in the concentrations of - p.p.m., were subjected repeatedly to surfactant replacement therapy (alveofact). results: ecmo was needed in no patient, patients survived, patient was disconnected from the ventilator because of brain death in spite of conspicuous improvement of oxygenation and other parameters, some relevant parameters hours before and hours after starting hfo are given in table ~ in all the cases, the disconnection from hfo was carried out through the simv regimen, never directly to cpap. table : the levels of blood gases, oxygenation index (oi), aado ,map,fio and pao /fio ratio hours before and hours after starting hfo. conclusion: although none of the patient had to be subjected to pediatric ecmo, hfo should be carried out only in workplaces having the immediate possibility of using this method in the case of hfo failure. speculation: should not hfo be used ir pediatric patients with ards earlier than aggressive cmv? can hfo ce considered standard, not experimental method of therapy? refractory hypoxemia in premature patients is characterized in a persistent elevation of pulmonary vascular resistance, with right to left shunt through the ductus arteriosus and or foramen oval. we report the case of a vlbw patient (ga w, bw g) who present a severe hypoxemia related to hyaline membrane disease and a pulmonary and systemic infection to group b streptococcus, refractory to conventional ventilatory support and surfactant therapy, associated to hemodynamic failure falling in ecmo criteria used for term infants. a rescue therapy with hfov (sensor medics a) is decided at h of live, the table resume the patient's evolution before and after hfov. at w of postgestational age the patient present a fio of . with a chest x ray compatible with a cld type l at discharge no oxygen requirements was needed and actually he's doing well. conclusion: hfov, using an adequate alveolar recruitment strategy, was effective in the rescue of a severe hypoxemic respiratory failure with a rapid off of ecmo criteria entry in our vlbw premature patient, during the united nmioffs embargo ~nst yugoslavia the prevalence of the ast}nnafic ~acks in c~dldren aratsed. the mo~t common causes have beem dramm~e worsening of life standard, ecom~c disaster in global community, gr~ number of refugees from the other parts of former yugodavia. it wm obviom that mcio-ecoumnical conditions took a part in the exacerbations of previously known cldldhood asthra~, ~av~ of micro-and m~mclimaflc changes, psychosocis] and emotional cryses, lack of medics-m~nts for p~ve~on and tl~rspy of acute asflanatic attacks. about % of d-dldv~ tmslod in our picu for these year~ exp~dvncod ~vcr~ attack for the flint time iu ~jzeir lifts. it has been cu~ ~%~ children in mspir~ry picu of our hos~mt. the scut~ revere attack (more ~asn ~/o of hight clinical score) was detected in % of all children admitted with respirak~ problems. from tl~ mmlysss we exclu&d: bmncldolifis, ~i anomalies, ~eve~ i~ccqions. concerning our drug supplies (which wc~e reduced), we started our therapy by administration of oxygen, ~ta -ago~dst inhalations (but sometimes we had the solution for jet nebulizcm only for o~e inhalation per p~cnt), mwinophyllin and mefl~ylpr~ini~done in/ravenously. % of ih~ asthmatics needed repea~ doses of muinophyl~n pinch.ally, tnch.,ding the fluids. the bronchodilak)r msponm was poor ~r~cl slow, hospital stay in picu was for days and for days in other units sl~rwsvds. tim ~ of their stable condifio~ was hard at borne (or refugees camps), without p~ventkm, so they came bsvk to hospital for morn than times in % of cases, dtrdng ~e je last motlfl~s file dtustion improved, concerning tim drugs supply for prevention, and we hope that these lifc~restening conditions wouldd~ introduction: the incidence of ards is increasing as survival of critically ill patients is higher. the application of new therapeutic modalities have increased the survival rates in (ards) adult patients. objective: to study the therapeutic efficacy of new tleamlents in children with ards material and methods: a retros~ctive study was conducted from to . children with severe ards, (lung severity score > , ) (r), aged days to years, were included. the diagnosis were as follows: interstitial pneumonitis, non interstitial lung infection, with lung aspiration and with clinical sepsis. patients had different tipes of cancer and to suffer inmunodeficiency disease, the first subjects (group t) were treated with conventional measures. from october of new therapeutic modalities were introduced, including: less agressive ventilatory support, postural changes (prone to supine) in subjects, administration of corticosteroids in patients, rfitric oxide in , pe~ssive hypercapnia and administration of exogeans sarfactant in one, pao /fio , d(a-a)o , oxigenation index (oi) and the score of respirator), severity disease were similar in both groups. the two groups evolntiou was compared. results: -ten patients died, from group i and from group ii ( % v.s. : %,ns). -the evolution time, either to exitus or weaning from ventilatory support was higher in group ii ( . v.s. . days in group i, ns), -the incidence of barotrauma was observed in subjects ( . %), from group i and from ii. of these patients % expired. -during the course of the disease, ( %) patients had more than one damaged organ. only in one subjet mof was considered to be the main cause of death. the majority of the patients expired because of their respiratory disease, although, % of them met criteria of mof. -fifty percent of the subjects were infected at the time of death. stmmry: a trend toward a higher survival rate is observed in the subjects receiving the new modalifies therapeutic intervention (corticosteroides, postural changes and permissive hypercapnia). our results are not significative,probably because of the small number of subjects studied. a new doubleaurae~t two-stage et-tube (dl-ett) was desig~aed and tested in the rabbits with acute king injury under conventional mechanical ~entilation_ ventilation efficiency of dl-ett was emrrpared with that of canveniionally t~sed single lumen et-tube (sl-ett). meth~s: dl-ett was specially made out of two sl-ett. vertical crosssections at the distal end of two et-tube (td _ rmn portax) were adhered with each other to form a tracheal stage lumen wifu id . mm the two remained uncut parts of the tubes corlntithted the oval s~ge with two separate imnens. dl-ett and sl-ett were randomly applied to five adult paralyzed rabbits with acute lung injury (by . nffkg oleic acid. iv). a bird inter vetffttator (bird products corporation) was used for time-cycled pressure-limited ventilation at /min of respiratory rate, ern h of peak i_~piratory pressure, l: of ire ratio, ljmin. of flow rate and . of fich. peak inspirntory pressure, mean mrway pressure, posi ve end-expiratory pressure at tip of et-mbe and bemodynamics were measured and recorded continuously. arterial blood and expired gas were measured ~by avl blood gas analyzer) after each stabilization t.~iod of minntes. _analysis w~as by prated t test. result: dl-ett acaltety improve cos removal at all amman. pa(?oz was decreased by t . +_t. (p< . l) and physiologic dead space fraction (v~zvt) reduced by % +- . % (p< . t), compared with dl-ett. there were no significant change in arterial oxygenation. conelus|on: the double-lumen two-stage et-tabe significantly increases ventilation effmiency with simple operation in rabbits v, ith acute hmg injury, lts availability may influence future clinical management of ~ennated patient~. this ~muly was fimded by the science and technology. commiuee of beijing municipality. analis of hemostasis alterations on different coagulation cascades in children with septic shock has shown that coagulation disorder character is dependent on lung affection rate. the initial manifestation of the respiratory distress-syndrome (rds) are characterized by the obvious activation of blood thrombin potential, moderate coagulopathy and not sharply marked endoteliosis, the witlebrand's factor (wf) increase tot - %. progress in the clinical picture of "shock lung" leads to chronometric and structural hypocoagulation with potential hypercoagulation in "mix-test", high level of firbin derivative, thrombocytopenia with thrombocytopaty and the wf increase to ~ %, terminal stages of the rds, as a rule, are characterized by potential hypercoaguletion absense, depletion of at-lit and plasminogen, prevalence of antithrombin and antiaggregating activity, obvious endoteliosis (the wf to increase - %). the arteriowenous difference according to index of the thromboelastography (teg) in the rds ill-iv rates was , % less than in the - rates, disorder of lung filtering ability in severe rds is confimed also by minimal arterio-venous difference of activated euglobulin lyses (ael) in children with the rds ill-iv rates is only , %, while the patients whit rds i-i rates have the ael-activity in arterial blood , times as much than in venous blood. the use of then allows to determine the potential hypercoagulation rate, the at-ill level and fibrinogen quantity during the anticoagulant therapy and also the character of the x-factor activation and thrombocytic hemostasis. the effective therapy component of septic genesis rds in children is the controled coagulation method with the use of the individual selected heparin doses in according to desagregants, kryoplasma, proteolisis inhibitors and trombolytics. it is necessary to avoid the heparintherapy for children with the rds complicated with producting coagulopaties and termal phases of blood disseminated intravascular coagulation (dic). bronchoseopy has been used for evaluation of the potential problems of the airways and for investigation the bronchial specimens for diagnostic purposes. regent technical advances result in performing this procedure at the bedside manner and in critically ill patients. we have performed hronehoaeopy during last three years on pediatric patients with respiratory problems, in % of cases the opentube hroneh seopy was performed (for diagnostic as well as for therapeutic reasons) and collected secretions or bioptic material were examined. the indieatiuns were: acute upper respiratory problems, chronic wheezing, inspiratory strider, tracheal or bronchial bleeding, chronic eongh, retractable atelectssis, severe pulmonary infections, lymph node perforation in lung tuberculosis and soquells like bronehiectssis and fibrosis. our results were: anatomical malformations in %, mueosal oedema with chronic inflammation and thick secretions in %, easuos masses in %, granulation tissue and purulent secretions in foreign bodies and bronehieetasis in %, and only % of eases were normal finding. our exlxdenees pointed that this invasive procedure in carefully selected patients has important role in establishing the diagnosis and in the- introduction: tbg has been a useful investigation in the management of ventilator-dependent infants in our experience. one ml of contrast was hand ventilated into the respiratory tree via their nasotracheal tubes and their anatomy and dynamics demonstrated on radiological screening. case descriptions: three infants who were difficult to ventilate requiring high airway pressures, high peep and a significant oxygen requirement had tbgs. the ages ranged from to months. two cases were complicated by complex cardiac lesions. in all cases there were frequent episodes of desaturation, where hand ventilation proved difficult and various intermittent lobar collapses occurred. microlaryngobronchoscopies (mlb) performed on the infants by experienced paediatric ent surgeons failed to identify the airway problems. more than one mlb was frequently done. concern about introducing contrast into the airways of infants with limited cardiorespiratory reserve combined with an uncertainty about how much extra intbrmafion would be gained often led to a delay in investigation. when performed these fears proved groundless, the anatomy and pathology of the airways were demonstrated in full and the correct therapeutic plan started. in two cases tracheostomy and peep producing patency of bronchomalacic segments allowed weaning to low levels of ventitatory support. in one case tracheal reconstruction was undertaken and in the cardiac cases the respiratory component of the ventilatory dependence was fully assessed. at the age of months, a baby boy with a history of minor respiratory problems, was admitted to hospital with an upper airway infection and severe dyspnoea. shortly after arrival at the icu he had a total airway obstruction. after intubation there were still difficulties to establish a normal gas exchange, and he was tranferred to the regional picu. ct scan and bronchoscopy verified a congenital tracheal stenosis affecting the whole trachea except the upper mm below the vocal cords. the diameter was estimated to less than ram. an unsuccessful attempt was made to dilate the extremely rigid stenosis with a balloon. after the procedure he had a respiratory and circulatory arrest, and he was put on ecmo as a bridge to surgical correction. after stable days on ecmo, surgery was performed during ecmo with a tracheal homograft transplantation. immediately after surgery, ecmo was discontinued. a silastic dumont type stcnt was inserted inside the homogra~, and a nasotracheal tube was placed inside the stent for assisted intermittent mechanical ventilation. repeated bronchoscopies were performed to remove granulation tissue and secretions. at months of age, the stem was removed with an endoscopic procedure. however, the trachea was still soft and collapsable, and another silicon stent was placed inside the trachea for another months period, after removal he had some respiratory problems and he was treated with nebulized salbutamol, mcemic epinephrine and steroids. he was discharged from the hospital at months of age and his condition is now stable. this is the first procedure of its kind in sweden. it was accomplished by international and multidisciplinary collaboration. ecmo may be a bridge to corrective surgery and long time stenting may be necessary in the postoperative period. post mtubation laryngitis ( pil ) is still a frequent complication, occurmg in l - % of intubated patients. inhaled racemic epinephrine has for long been used as an accepted therapy, but this drug is not always available. the authors undertook a randomized, double-blind, placebo-controlled trial to determine the efficacy of inhaled l-epinephrine(le) in the treatment of plu in the period between july/ and may/ , patients were submitted to endotracheal intubation for ventilatory support. atter the extubation procedure patients were considered for enrollement if they met the following criteria: clinical signs of laryngeal estridor and a downes and rafaelly score for upper respiratory obstruction equal to or higher than patients with primary upper respiratory disease were excluded all patients enrolled reeieved either inhaled l-epinephrine % or normal saline. dexametasene ( , mg/kg/day) was given to all patients in both groups. after inhalations, au patients were monitored for a period of - minutes and monitoring included cardiac and respiratory rate, mean arterial blood pressure, arterial blood gases and the dowries and rafaelly score. statistical analysis included, qui-square with the fisher correction test and the z-test for paired variables. thirty eight patients ( , % ) met the criteria for enrollment, to the le group and to the placebo group.there were no significant differences in both groups in regard to age, sex, initial score ( , x , ) and endotracheal tube diameter. the period of ventilatory support and tracheal intubation was significantly higher in the le group ( , x , , p = , ). the follow-up score showed a significant drop only at minutes after the inhalations (p = , ). re-intubation due to laryngitis, occured in patient of the le group and in of the placebo group with no statistical sxgnificance (p = , ). no difference was observed on the monitored hemodynamic variables during the minutes, except for the mean arterial pressure at minutes, being heighar on the placebo group (p = , ). we concluded that, although the l-epinephrine group showed a trend in better scores post-inhalation and fewer re-intubations due to laryngitis, the results were not statistically significant. we especulate that the period of intubation may have affected our results. similarlly there were no differences in the incidence of adverse effects between both groups. objectives:to evaluate the complications of endotracheal intubation in children with upper airway obstruction due to epiglottitis or croup. methodes: during a year period ( - ) all patients with epiglottifis or croup were reviewed to determine the complications of endotracheal intubation, especially upper airway obstruction due to granulomas. results: patients were reviewed. in children (mean age . years) with epiglottitis the mean duration of intubation was . days ( - ). no complications were seen. in patients (mean age . years) with croup the mean duration of intubation until the first extubation was . days ( - days). elective extubation was performed if an airleak was present or after days without airleak but in the absence of fever and obvious secretion. reintubation was not necessary in children ( . %). in this group the mean duration of intubation was . days ( - ). in patients ( . %) reintubation was necessary because of severe upper airway obstruction due to granulomas. mean duration of intubation until the first extubation was . days ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . there seems to be a difference in duration of intubation between these two groups with croup, however it is not significant (p > . ). all the patients with granulomas could be successfully extubated after microlaryngeal surgery, with a mean intubation period of . days ( - ). revealed no complications, where as endotracheal intubation in children suffering from croup showed a high incidence ( . %) of granulomas. however laryngeal steepsis and other serious complications were not sesn~ patients ( days averagely] was obviously seen in ~he peak =one of fl, f resonance and in the zone of high freq,-~ncy :r, ~;~e composition while cases( day~ average;y] :~bowed no abnormality both clinically and isryngoscopica!~y. / patients with catheter placement for more than week~ end p~tie,~ts for less than weeks had t;~ryngeal abnormal change in their larynges,abnormal changes of sound spectrogram were all seen in patients with placement for mope than weeks. our data suggest= ca] the complication of endotracheal intubation was increases with increasing length of time of catheter placsm. entjbut aeriuoa complication is rare i (b] the time limit of pernasal endotraoheal catheter placement is weeks within which the procedure is • comparatively safe and effective means for maintaining e tong term artificial airway. in a -year period ( ) ( ) ( ) ( ) ( ) ( ) ( ) we diagnosed tbm as an apparent dilatation of the trachea and main bronchi ih four premature infants on continued mv for respiratory distress syndrome (rds). the infants were three boys and one girl with gestational age (ga) - weeks and body weight (bw) - g. mv was provided by bourns cub time-cycled and pressure-limited ventilator to attain normal gas tensions. no jet ventilation was used. chest radiographs were reviewed for a complete evaluation, and for the evaluation of the airway. after the intial subjective diagnosis of tbm, the width of the tracheal and main bronchial air column was measured at the lower level of the first and the third thoracic vertebal body it , t ) and near the carina; the width of the main bronchi below the carina was also measured. in all infants, tbm became apparent close to the lh day, that is, after - weeks of mv. therefore, for the time period from birth to the th day the following ventilatory parameters were reviewed and analyzed: ( ) the percentage of total ventilation time when more than % o concentration was required, ( ) the peak inspiratory pressure, ( ) the positive end-expiratory pressure, and ( ) the duration of high frequency ventilation ( - breaths per minute). also noted were the apgar scores ( and min after birth), the duration of hypotension (systolic bp below mmhg) and circulatory instability, the presence of systemic or tracheal conatal or later infection, the duration of mv, and the final clinical outcome. the records were also reviewed for other possible pertinent data. rigid respiratory endoscopy in children fraga j, amant a s, piva j, nogueira a, palombini b. introduction: the respiratory endoscopy is an important procedure to diagnose and treat many airway's diseases in children. although have had advances in radiologic investigation exams and pulmonary function tests, the direct anatomic visualization of airway is important to the management of many respiratory problems. objective: evaluation the respiratory endoscopies performed with a rigid bronchoscope in a pediatric reference hospital. material and methods: we study the records of all children that were submitted to respiratory endoscopy under general anesthesia from march to march . age, sex, clinical to indicate the procedure, diagnosis and complications of endoscopy were registered. results: three hundred and fifty six respiratory endoscopies were performed. the most common indications for endoscopy were strider ( %), suspected foreign body ( %), atelectasis ( %) and difficult tracheal extubation ( %). the most frequent diagnosis were laryngomalacia ( %) and subglottic stenosis ( %) in the glottic and subglottic areas, and foreign body ( %) and tracheomalacia ( %) in the tracheobronchial area. normal endoscopy was performed in ( %) of the children. only three slight complications of the endoscopy were observed. two patients presented bradycardia during the exam, and the third need tracheal intubation due to post-endoscopic subglottic edema. conclusion: the rigid endoscopy in children is efficient and has no serious complications. near drowning; indicators of acute and long term prognosis bernardien t.mj. thunnissen t, reinoud j.b.j. gemke , loes veenhuizer?, krijn haasnoot , a.johannes van vugh department of pediatrics, ~wilhelmina children's hospital, utrecht, sophia hospital, zwolle, and ~free university hospital, amsterdam, the netherlands. in this retrospective study factors that affect short and long term prognosis after submersion were analysed. all patients that were admitted to a tertiary pediatric icu between january i, and january i, were included. of patients, aged - years, died in the icu, one after hospital discharge. survivors and non-survivors showed significant differences with respect to central temperature, pupillary reactions, arterial ph, pediatric risk of mortality (prism) score and therapeutic intervention scoring system (tiss) upon admission (p < . ). non-survivors more frequently required mechanical ventilation, bicarbonate administration and active reheating. ards was seen in patients ( %), invariably within hours after admission. no patients with cardiac arrest on" admission snrvived without sequelae. hypothermia appeared to have no protective effect on hypoxic damage. survivors with persistent sequelae _> months after discharge had significantly higher prism and t ss scores (mean and , respectively) than those with complete recovery (mean and , respectively). long term cognitive problems were present in / survivors ( %) and emotional disturbances in / ( %). in conclusion, a concise number of clinical and laboratory parameters, representing acute severity of illness, are important prognostic indicators for survival and health status of children after submersion. there were ( %) bronchoscopies, and ( %) were oesophagoscopies.the average age was , years for bronchoscopies, and years for oesophagoscopies. the outcome of the patients was good. no complications were observed. extraction is recomended in every symptomatic patient. orphenadrine is an anticholinergic drug mainly used to decrease symptoms of parkinson disease. orphenadrine has a peripheral and central effect and overdose can result in athetoid movements, convulsions, cyanosis, coma, arrhythmias, shock and cardiac arrest. physostigmine is a specific antagonist of the peripheral and central effects and can be a useful antidote. we report the case of a two and a half year old female who was transfered to our icu for general convulsions. the little girl had, three hours before admission, accidently ingested rag of orphenadrinehydrochlodde (disipal®), which was her grandmothers anti-parkinson medication. three hours after ingestion she presented neurological signs: confusion, unstable walking, and periods of aggression. generalized tonic-clonic seizures appeared who were rebel to administration of multiple anti epileptica but ceased after iv administration of diazepam and endotracheal intubation and ventilation. an episode of ventdcular tachycardia responded well to the iv administration of tidocaine. the levels of orphenaddne in the serum were high at admission ( pg/l) and were present in the blood up to hours after ingestion. high serum levels are, in the literature, associated to a high mortality rate. physostigmine was administered three times at a . mg/kg dose in the first hours. we decribe the noted effects of physostigmine on the different symptoms. the patient survived and could leave the icu after one week. in conclusion: orphenadrine poisoning is a very complicated medical problem associated with high mortality. in severe intoxication, the benefit of physostigmine more than counterbalances its side effects. objective: to define the optimal volume of dilution for endotracheal (et) administration of epinephrine (epi) design: prospective, randomized, laboratory comparison of four different volumes of dilution of endotracheal epinephrine ( . , , and ml of saline) setting large animal research facility ofa universi~ medical center subjects and interventions: epinephrine ( . mg/kg) diluted with four different volumes ( , . . and i rot) of normal saline was injected into the et tube of five anesthehzed dogs. each dog served as its own control and received all four volumes in different sequences at ieast one week apart. arterial blood samples for plasma epinephrine concentration and blood gases.were collected before and . , . . . _ . . , . . , . , . , and minutes after drug administration. heart rate and arterial blood pressure were continuously monitored. measurements and main results: higher volumes of diluent ( and i ml) caused a significant decrease of pao , from :!: tort to ±i torr, compared to the tower volumes of diluent ( and ml), from ± torr tu +_ torr (p< . ). these effects persisted for over minutes. mean plasma epinephrine concentrations significantly increased within seconds following administration for all the volumes of diluent. mean plasma epinephrine concentrations, maximal epinephrine concentration (cmax), and the coefficient of absorption (ka) were higher in the ml and ml groups. the time interval to reach maximal concentration (tmax) was shorter in the ml and ml groups. yet these results were not significantly different. heart rate. systolic and diastolic blood pressures did not differ significantly between the groups throughout the study. conclusions: dilution of endotracheal epinephrine into a ml volume with saline optimizes drug uptake and delivery, without adversely affecting oxygenation and ventilation. the aetiology and outcome of paediatric out-of-hospital cardiac arrest was studied during a -year period in southern finland served by physician staffed emergency care units. the files of prehospital patients less than years old without palpable pulse and spontaneous respiration were analysed retrospectively. fifty patients were declared dead on the scene (dos) and resuscitation (cpr) was initiated in patients. the sudden infant death syndrome was the most common cause of arrest ( %) in the dos patients as well as in patients receiving cpr ( %). asystole was the initial cardiac rhythm in % of the patients in whom cpr was attempted. eight of the hospitalised patients were discharged, of them with mild or no disability, with moderate disability and one in vegetative state. in multivariate analysis the short duration of cpr (< minutes) was the only factor significantly associated with better survival. due to various aetiologies the survival rate from prehospital paediatric cardiac arrest is quite low. on the other hand, hypothermic near-drowning victims seem to have a relatively good prognosis. duration of cpr less than minutes was the best predictor of intact survival, our study supports the previous findings of the importance of early and effective resuscitation efforts for establishing ventilation and perfusion on the scene. in our system well trained physician staffed emergency care units are able to provide immediate and effective als on the scene. on the other hand, these units also appear to be able to refrain from resuscitation when the prognosis is pessimistic. objective: to assess the normal ,gastric intramucosal ph ~hi) by tonometry in healthy children patients and methods: twelve healthy children ( males and females) with age rmaged from months to years scheduled for minor plastic or urologic surgery. children were previously medicated with midazolam ( . mg/kg) and atropine ( . mg~) both i.m.. anaesthetic induction was standardized with -n ( %) administered via facial mask and increased halotane concentrations (up to %). all patients got an endotraeheal tube after iv. administration of femanile ( mcg:jkg) and vecuronium ( . mg/kg) or suxametonio ( mg/kg), pmaesthesia was maintained with o -n ( - %) and isofluorane ( . - %). during surgery, children needed mechanical ventilation and the others maintained spontaneous breathing. ekg, heart rate, blood pressure, and pulse oximetry were moniterized. after anaesthesia, a sigmoid tenometry catheter (tonometrics, inc.) was inserted in the stomach of the patients by direct visualization with laryngoscope and magyll clamps. children were all maintained normoventilated and with normal cardiorespiratery variables. cadet's balloon was £~led with . ml of saline. thirty minutes after the insertion rrd was extracted and rejected, just afterwards the remanent . ml was extracted and immediately analyzed. simultaneously an arterial gasometry by puncture was performed. gastric phi was calculated by the henderson-hasselbalch's equation using the pco obtained from the tenometry catheter and the bicarbonate value obtained from the arterial gasometry. results: average gastric phi was . -i- . , range ( . - . ). objective: demons~ating intramucesai ph (phi) alterations during transport of patients from operative room to pediatric intensive care unit (picu), material and methods: phi measurements were performed with gastric tonometer catheter in t patients undergoing cardiac surgery with cardiopulmona d" bypass (cpb), there was mate and female, the average age = yl ra, average weight = , kg, average time of cpb = rain. the measurements were made at the end of the surged' and when the patients had arrived in the picu statistical aualysis: average and ~andart deviation and test "t" student. objetive: to asses the efficacy of gastric iatramucosad ptt (phi) and arterial lactate levels to evaluate splacalc tissular perfusion in an experimental model of intestinal ischemia. suneets ~nd methods: twelve piglets weights t - kgs. undergoing orthot~ie liver trasplantation. the intestinal ischemia was induced by aortic damping. tonometry catheter (tonometrics inc.) w~s placed in the stomach after artaesthesia and ot intubation. phi ~s determined times and lactate levels was determined fi times in stages: i) pre-ae~hepatic stage (twice: before surgery and before aortic clamping ); ii) end anhepatic stage (only phi): iii) reperfusion stage (a , , and minutes). the phi was derived from application of the henderson-hassdbach formula using the pco value from the tonometer and the arterial bic~rbonate. all pipets received raaitidiila before sttrgery. values of phi above , and lactate levels between and mg/dl were considered nortrm. the results were statistically anaj.izated with anova and bonferroni tests. results: the phi was normal on pre anhepatic stage (> , ) and lactate levels were slightly increased ( , +_ , and , ± , mg/dl ns) . in relalion to we-anhepatics values, phi decreased signncatly at the mid of anhevatic stage ( , _+ , vs , _+ , p< , ), phi remain low in stage iii, at rain ( , + , p< , ) and min(g -+o, p< , ). arterial lactate levels increased significatly in relation to levels in stage i, at rain ( , _+ , p< ,o ) arid rain ( , ± , p< , ) of reperfusion stage. there is a slight improvement on phi and lactate ievels at and t rain althought the differences did not reach significance. cnmments: phi and arterial lactate levels propperly reflect hypoperfusion on the experimental model of acute intestinal isdlemia. b~kground : the paediatrie gallbladder diseases generally described are calculous ¢hol~tstitis, cystic duct obstruction, congenital anomaly of the biliary tract, and inflammation. in the neonatal period, noulithogenie gallbladder disease could be also due to erythroblastosis or hyperalimentation. obieetive : we describe an other type of disease affecting the gallbladder in neonates thought to be related to their vascular vulnerability. methods : four patients with abnormal gallbladder ultrasound not related to classical observations were included. we have studied and reviewed the biological and clinical data, the ultrasound findings and their evolutions. results : four patients, to ~.k-old neonates ~ffth a birthweight be~,een , and , kg, were intubated and under total parenteral nutrition for to days. none of them were symptomatic on repeated clinical evaluations. one newborn developped hypotensien on umbilical bleeding at hours of life. in two cases, signs of cholestasis were discovered : the total bilirubin level has risen to mg/dl; the direct bilirubin level was , mg/dl while the urina were dark and the ~o~,ls :mcolour~. the c~mplct~ ~crology as a!! the culvare~ remained negative. the ultrasound explorations were atypical : in the four eases, an initial increasing broad and thickness of the wall of the gallbladder with an hyperecbogenie inside content, which was not sludge, was discovered. in three eases the images resolved in ten to fifteen days. in one ease, an asymptomatie thrombosis of the vena portu which remained patent was discovered. in this case, at one month, the ultrasound showed images encountered in chronic ebolecystitis and, at one year, the gallbladder appeared atrophic. none of them underwent surgery. conelusiou : the gallbladder diseases are multifactorial. besides the prematurity, the infections, the total parenteral nutrition, the premature neonate is exposed to vascular vulnerability affecting also the gallbladder and this may explain our findings. progress in prognosis of pts with b-nhl had followed the use of multimodality chemotherapy (ct). with the prolonged survival, there are comlications due to myetosupression & desease process. the syndrome of neutropenic enterocolitis (ne) is one of the ominous problems because ofpts increased susceptibility to infection & overwhelming sepsis. this material included neutropenic pts ( - years) with the stages iil& iv of b-nhl who were treated with the modifired bfm- (mtx g/m in -h inf.); males, females. seventeen episodes of ne were observed & only after the first courses of ct ( of after tst, %; of after nd, %). the symptoms existed to days. wbc ranged from to in l~tl (median, ). the first signs of ne were directly correlated to the beginning of the neutropenia & the recovery of neutrophils led to the disappearance of abdominal recovery of neutrophils led to the disappearance of abdominal pain. the conservative treatment included gastrointestinal tract decompression, broad spectrum antibiotics initially, volume & electrolyte substitution, nutritional support, correction of acid-base balance, symptomatic treatment. sixteen pts were treated nonoperatively, died. on autopsy the transmural bowel necrosis due to thrombosis of branches of a.mes.sup, was found. the bowel perforation occurred in one patient, he was undergone laparotomy & hemicolonectomy & survived. we conclude that ne is a frequent complication in neutropenic pts with the st. lii& iv of b-nhl. it occurs after the induction courses of ct. close observation by surgeons, oncologists & pediatric intensivists is mandatory. conservative treatment is effective & more preferable until leucopenia resolves. operation is necessary only for those.with perforation. near infrared spectroscopy as a tool for evaluation of intestinal perfusionpresentation of an animal model. c. scheibenpflug, p. buxbaum and a.m. rokitansky the recent development of and investigations in the so called near infrared spectroscopy ( nirs --transcutanous emission and simultaneous registration of intensity of spectralcolours depending upon modulations of tissue perfusion ) enable physicians to measure and qualify organ perfusion and nowadays is mainly used to control cerebral as well as skeleton muscular blood flow in trauma patients at intensive care units ( icu ). today intestinal perfusion, hypoperfusion , cell damage caused by reperfusion injury, bacterial and toxin translocation are serious problems in critically ill patients at an icu. paediatric intensive care physicians put major concern on intestinal perfusion, which for. instance gains more and more importance, especially in the neonatal period for example as an etiologic factor for necrotizing enterocolitis. we established an animal model, in which we measured intestinal perfusion by nirs under various invasive and noninvasive conditions. methods and results will be referred. for preliminary conclusion we propose near infrared spectroscopy ( nirs ) also as a potent diagnostic tool to determine early intestinal malperfusion in order to prevent lethal outcome. fm'ther investigations in animals as well in paediatric iritensive care patients should be done to estimate our efforts. introduction: following the acute phase of necrotising enterocolitis (nec) starvation of the gut for a period up to weeks is a generally accepted treatment modality in many centres. objective criteria to refeed these patients are hardly available. recently the double sugar test has become available as a parameter for (ab)normal gut permeability ~' . aim of the study: to evaluate the changes in permeability of the small bowel in patients with nec and controls before introduction of enteral feeding. methods: a lactulose! rbarrmose (i/r) test was performed in two groups. group was studied - times within a -week period of starvation (n= , mean gest. age , range - weeks). in group seven different control patients were studied (mean gest.age , range - weeks). the test was performed by giving a patient after at least a hour fast ml/kg bodyweight l/r solution and determination of the /r ratio in a -hour urine sample by chromatography. results: objective: to evaluate the prognostic factors in the response to nitric oxide (no) in children with acute respirator/ distress syndrome (ards) and/or pulmonary hypertension (pht). patients and methods: critically ill children received no inhaled for ands and/or pht treatment. patient before and after cardiac surgery ( cardiac transplants), with bronchopneu~onia, multiple trauma, sepsis and cardiorespiratory arrest. patients showed /j~ds and pht, in with associated ards. we analyzed age, sex, diagnosis, pao , pa /fi , oxygenation index, pht, shock, and sepsis as prognostic factors and response factors to n . results : after no administration oxygenation did not improve in patients ( . %) and pht did not diminishe in one children ( %). patients survived ( %), / ( . % with /d%ds) and / ( %) with pht. the four patients with isolated pht survived , and the patients with pht and ards dead. patients after cardiac surgery presented less mortality ( . %) than the rest of patients ( . %). patients with shock presented higher mortality ( . %) than the rest of patients ( . %). there are no differences in response to no in respect of sex, age, diagnosis, shock, and sepsis. survivors showed higher increase of pao /fi . ± . to no than non-survivors . ± . (n.s). patients with pht showed higher increase in pa /fi to no administration ( ± . ) than patients with ards ( . ± . ), (n.s), but patients with ards showed a higher increase in !, ± . , than patients with pht . ± (p < . ). patients with pa /fi < i showed less increase in pa /fi , . ± . , than the rest of patients . ± . (n.s) conclusions: i. mortality of isolated pht treated with no is less than patients with ap~s. patients with shock and those with pht and ards showed higher mortality. . we have not found any clinical or analytical factor to predict clinical response to no administration. patients showed ards, and severe pht after cardiovascular surgery, in with associated ards. we registered respiratory assistance, blood gases, pao /fi , the oxygenation index (oil, and mean pulmonary pressure/ mean systemic pressure (pap/sap) before and after no inhalation. we measured continuous concentration of no and no by electrochemical method (noxbox, bedfont, airliquide). results: no administration improved oxygenation mean pao from ± tm~g to i ± ~g (p < . ), mean pa /fi fr<xa ~ to £± (p < . )and i from ± to ± (p < . ). patients did not improved with no administration. the oxygenation improved in the first five minutes and the best oxygenation was achieved with - ppm. there is no significant change in pac . pap/sap diminished from ± % to ± % ( p< . ), in one patient there is no response. the no administration was maintained between ~ minutes to days. the effect of no on pulmonary pressure and oxygenation was maintained without change during all the time it was administrated. n concentration were always less than ppm y metahemoglobinaemia less than . %. there are no side effects secondary to no administration. patients survived ( %). concluaions:l.administration of no improves oxygenation in children with ~/eds and diminishes pht after cardiac surgery. .no effect is fast and maintained during the evolution. high frequency oscillatory ventilation in combination with inhaled nitric oxide g~thberg sylvia, md, edberg k e md, phi), dept of paediatric intensive care, children's hospital, s- g teborg, sweden background: for man), years severely sick infants with congenital heart malformations or acute lung disorders have died due to pulmonary hypertension, hypoxia and multiple organ failure. today there are several therapeutic facilities coming up for these infants. ecmo progranunes have been introduced in severul centres as well as improved venlllatory techniques, as high frequency oscillatory ventilatior~ (hfov), which provides adequate ventilation with less risk for hmg injury.. in , the endothelium derived relaxing factor was identified as nitric oxide (no), and extensive studies have sho~-a that inhaled no reduces pnimonm o vascular resistance and improves oxygenation in hypoxic infants with pulmona~ hypertension. material.. from july to january , we have treated severely hypoxic children with combined ttfov-no. seven were newborn, with cdh, one with mas, one with irds, one with paediatric ards due to rsv infection and one with poor oxygenation atler open heart surgery. were between month and years and all had ards of differentorigin but one who was hypoxic after open heart surgery. method: hfov was given by means of sensormedics a oscillatory ventilator to patients, and dr~ger babylog was used in one case. mean airway pwssures varied from - cm h . oscillatory pressures varied from - cm h and ventilatory rates from - hz. fi o varied from , - , . no was administered by nomius classic. no and no was measured in the inspiratory limb with an electrcchemieal device. noconcentration varied from to ppm and the no -concentration between - , ppm. methemoglobin was never more than , % (average , ). duration of treatment varied from to days. combined trealment with hfov and inhaled no improved oxygenation and carbon dioxide elimination in out of treated childretl patients died, due to their underlying congenital heart disease, one of asphyxia due to rsv-infection and one of cdh with progressive hypoxia and multiple organ failure. combined treatment with hfov and inhaled no improves oxygenation in severely hypoxic children. treatment should be slarted early to reduce the risk for chronic lung injury following barotranma and high oxygen concentrations. we speculate that the combined hfov-no may reduce the use of ecmo, and that it may improve outcome in ceotres where ecmo programmes are not introduced. apart from its vasodilative properties nitric oxide appears to act also in physiologic immune defense. intracetlular concentrations of no synthesized by macrophages are in the range of above those produced by vascular endothelium. we investigated the bacteriostatic effect of nitric oxide at concentrations used during inhaled therapy for pulmonary vasodilation in neonates. ten different strains of five species were used (staph. anrens, staph. epidermidis, strop. group b [gbs], e. coil and pseudomenas aeruginosa), which are ~e most often tracheally isolated bacteria in mechanically ventilated premature infants and neonates. we compared bacterial growth of cultures applying three different concentrations of nitric oxide ( ppm. ppm, ppm) m the growth of the same strains in room air for a duration of hours. no bacteriostatic effect was demonstrable at no concentratioes of ppm. e. coil showed decreased bacterial growth at ppm and ppm, however without reaching statistical significance (p= . ). at nitric oxide concentrations of i ppm staph. epidermidis and gbs grew significantly less as compared to colonies of the same strains in room air. no effects were found regarding the growth of staph. aureus and pseudomonas aneruginosa. we conclude that nitric oxide has a selective bacteriostatic effect on some of the most often trachealb, isolated bacteria in premature infants and neonates. this effect appears to be dose-dependant and occurs in the upper range of dosages used with inhaled no therapy. further research is required in order to examine the mechanisms of action as well as specific interactions between different strains of bacteria and nitric oxide. the no,box monitor (bedfont, kent, uk) is used to monitor nitric oxide (no) and nitdc dioxide (no ) during no administration in ventilated neonates. according to the manufacturers specifications the monitor can be applied in cases where airway pressures range from to mbar. we investigated in-vitro the accuracy of the no monitor in a range of ventilatory conditions. using a dr~ger babylog we ventilated an artificial lung. no was administered { ppm no in % nitrogen) with a mass flow controller to the inspiratory tube, at a distance of cm from the y-piece. the no target value was set to ppm. the ventilator was operated in both cpap and ippv modes at different settings. the no sampling tube was placed on two different locations; in the inspiratory tube dose to the y-piece; in the expiratory tube haft way between the y-piece and the ventilator. the no-monitor was ca)ibrated with ppm no at mbar. fig. and show the sensitivity of the no-monitor for respectively static pressure (cpap) and pulsatile pressure (ippv) with the sampling tube located in the inspiratory tube. fig. shows the resur for pulsatile pressure with sampling in the expiratory tube. we conclude that the accuracy of the bedfont no-monitor is dependent upon airway pressure and sampling site, the latter possibly caused by incomplete mixing, pressure and no are linearly related when sampling occured further away from the administration site. based on this study we suggest to place the sampling tube in the expiratory tube. during neonatal care the clinician should be aware of varying inaccuracies depending on the respiratory pressures. hypothesis: availability of therapy with inhaled nitric oxide (ino) decreases ecmo use in patients referred .to a tertiary care hospital for treatment of respiratory, failure unresponsive to conventional therapies. background: at children's hospital of wisconsin (chw) treatment for patients who have failed conventional treatment for respiratory failure, sometimes called "rescue" therapy, has included ecmo since and high frequency oscillatory ventilation since . ino has been in experimental use at chw since may of i and has resulted in the perception of a decreased need for ecmo therapy in those patients referred for rescue therapy. this study was designed to tbst the validity of that perception. study type: retrospective cohort. methods: the medical records of all patients referred to chw from /lj to / / for rescue therapy for severe respiratory failure were included in the chart review. data were collected regarding diagnoses, illness severity, hospital course including interventions and complications, and outcomes. exclusion criteria w~ere the finding of structural heart disease or congenital diaphragmatic hernia as the basis for hypoxemia. qualification for ino treatment included an a-ado - or oi ~- for two hours or -> for twelve hours and echocardiographic demonstration of persistent pulmonary hypertension of the newborn. patients were classified into two groups based on the availability of ino at the time of their hospitalization. results: in the time period of the study, patients were referred for possible ecmo therapy. twelve patients greater than weeks old, with congenital diaphragmatic hernia and with congenital heart disease were excluded from this analysis, leaving patients for study, ino availability reduced ecmo use from of ( %) patients in the ~ino unavailable" group to out of ( . %) patients in the "ino available" group, p=& by fisher's exact test. the fact that the two groups were composed of patients of similar severity of illness is reflected by comparable rates of ecmo and ino rescue therapy ( % vs. %). conclusion: by providing an alternative rescue therapy, ino has reduced the need for ecmo in this group of neonates referred for respiratory failure. introduction: true hepatnrenal syndrome (his) is defined an acute renal failure {arf) in the presence of severe liver disease without other known causes of renal failure. hrs is frequently seen in the course of hepatic cirrhosis• in children, cirrhosis is rare; however, arf can be seen in combination with aseites and liver dysfunction• we describe patients with hepatic dysfunction and aseites in combination with ar~ and abnormal sodium-water handling, leading to the diagnosis of hrs. pathophysiology: three factors are considered in the pathogenesis of hr~: i) hepatic dysfunction, ) deranged hemodynamics, including abnormal blood pressure, reduced effective arterial blood volume and abnormal blood flew distribution, and ) neuro-humoral dysrsgulatiom, including elevated levels of aldosteron, renin, angiotensin-ll, ade, vasodilatim nitric oxide and vasoconstrictor peptide endothelin-l. the main pathogenetic feature is decreased cortical renal blood flow, decrease of glomerulur filtration rate (gfr), vastly increased sodium retention, uliguria, and azotemia. treatment: therapy is based on counteracting sodium and fluid retention by highdose aldosteron antagonists and loop diuretics, improving renal perfusion by lowdose dopamin, and strict restriction of fluid and sodium. interventions as paracenteals of aacites or n peritoneo-systemic shunt are associated with high morbidity and poor outcome in children. reversal of hem by conservative measures can only be attained at early stages of hrl liver transplantation is the only definitive treatment that can reverse ere at advanced stages. patients: the described patients developed severe ascites with insidious renal dysfunction and abnormal sodium-water handling during admission at picu and fullfilled clinical criteria fur hrs. treated according to the cited principles, all patients showed improvement of gfr, with increased natriuresis and gradual decrease of ascites. eventually, renal function normalised completly. conclusion: ere deserves greater recogmitimn in the picu population; diagnosis can be suspected on clinical criteria. with this increased awareness, therapy tun be instituted at an early phase, with better prospects for recovery. positive outcome of hem depends on early recognition of the clinical picture, understanding of the pathophysiology, and early institution of consistent treatment. mtx is an antimetatxflite widely used as chemotherapeutic agents. high dose ivitx (i to ~m ) administered as a prolonged intravenous infusion (over - hours), is often used to treat malignant paediatric diseases. major complications of this treatment are myelosuppression, orointestinal mucositis, dermatitis and impairment of anal function. we report two cases of mtx overd~age occurred in two children ( -year-old. month-old) t~ted for acute lymphoblastic leukaemia. they were treated by cavh and the mtx bhk~d levels rapidly decreasedavoiding multisystemic involvement. establishment of alkaline diuresis and monitoring of plasma mtx levels during treatment is essential to prevent nephrotoxicity. however. leuco',cnn rescue may not prevent the development of potentially lethal toxicities in patients with mtx concentrations persistantl} exceeding t mm. in theses cases, em'ly treatment of mtx intoxication may pm~cnt myelosuppression and reducerenal damage. the goal is to lower the concentration to below mmoll, at which time rescue agents aleme would be expected to be cllcctive. respective indications of these remo',at mctny.:is are still discussed : hacmt~ialysis t~ eharc(~l haemoperfusion should be prolx',sed for massive and acute intoxication. however, rebound has been reported after combined hcmodialysis and hemoperfusion. exchange transfusion may be proposed as a treatment for prolonged and moderate intoxication. peritoneal dialysis is an incflbedve method for remo~ al of mtx. cavh was used in our icu. cavh is a simple method for blood purification and n':dy iluid control. use of cavh was never be reported in this indication to our knowledge. simplicity, rap~d application and gco.l clinical tolerance are the main advantages of this technique. the technique presents ~peclal advantages in terms of low priming volume of extracorporeal circuit, low blood flow, low rate heparinisation. our results show a decreaseof plasma mtx concentration and a rapid reduction of halfqite of elimination (t hours over the period of cavh). moreover, we didn't delec~d rebound after stopping prc,xedure. small size of the i:ratients may present sometime special problems, but these technical problems can be overcome, no severe complication (needing, inlection) were observed during filtration, in summary, aggressive intravenous fluid hydration and alkaliniaation of the urine coupled with careful monitoring of renal function and plasma mtx concentrations during and al'tcr infusion along with lem~overin rescue has reduced the inndcace of life-threatening toxicity after highdose mtx. however, some mtx inu>xication still occurred, leading to se~em toxicity, particularly nephrotoxicity. in these cases, we think that cavh (or cavhd) is a reliable, rapid method without rcix~und increase in plasma mtx concentration or important adverses effects compared to other procedure removal. gouyon jb, germain jf, semama d, pr vot a, desgres j preliminary limited data suggested that hemofiltration and hemodiafiltration may be valuable in some neonates with decompensation of maple syrup urine disease (msud). venovenous hemofiltration (vvhf) and hemodiafiltration (vvhdf) were performed with a new neonatal hemo(dia)filter (miniflow , hospal) on anesthetized rabbits infused with branched-chain amino acids (leucine, isoleucine and valine) and c~-keto-isocaproate. the bcaa and aketo-isocaproate blood levels were close to those previously observed in neonates with msud when extracorporeal blood purification was required. vvhf and vvhdf performances were assessed with two different blood flows (qb = . and . ml/min). vvhdf was performed with dialysate flow rates (qd = , , . , . and . l/h). thus, each animal was submitted to successive procedures. within each studied period, clearances of the bcaa were strictly similar. bcaa clearances obtained by vvhf were similar to ultrafiltrate rates (respectively, . - . and . - . ml/min at high and low qb ; p < . ). the ~x-keto-isocaproate clearances obtained by vvhf were . - . and . - . ml/min at low and high qb (not significantly different). whatever qd value, the vvhdf procedures always allowed higher bcaa and c~-keto-isocaproate clearances as compared with the corresponding v'~hf period with similar qb. bcaa clearances obtained by vvhdf with a . l/h dialysate flow, were . - . mljmin and . - . ml/min at iow and high qb, respectively. the concurrent a-keto-isocaproate clearances were . -,. , ml/min and . _+ , ml/min. at both qb regimens, bcaa clearances provided by vvhdf were markedly higher than values previously obtained with peritoneal dialysis in human neonates with msud. the management of renal failure in the newborn is difficult. when dialysis is instituted peritoneal dialysis (pd) is usually the technique of choice. this is can be problematic and impossible in some patients with pre-existing intra-abdominal pathology. continuous arterio-venous haemofiltration (cavh) has been described in infants but sick preterm infants are not able to support the circuit. i have devised a means of having pumped haemofiltration in small/preterm infants (phis/pi) and describe its use in nine patients ranging in size from to gms for periods of to days. vascular access was achieved through or guage cannulae in either a peripheral artery and a central vein or through two central veins. blood was pumped out using an ivac infusion pump and through a gambro fh haemofilter. a second ivac pump was used to remove haemofiltrate from the filter and a third to infuse replacement solution. removal rate was set to give a clearance of mls/min/ . sq.m and blood flow rate set to between and times the removal rate. heparin was infused into the circuit to prevent clotting of the filter. biochemical and fluid balance control was achieved in all infants. guaranteed fluid removal allowed the administration of full nutritional support. four patients died when treatment was withdrawn because of an untreatable underlying problem. one recovered renal function but died some weeks later from unrelated problems, three survived and recovered renal function and one patient is still on treatment. this system allows a secure means of achieving fluid and electrolyte control in the preterm infant. the use of this technique may allow haemofiltration to become as applicable to preterm infants as it is to older children and adults. unibrtunately, children often receive no treatment, or inadequate treatment for pain and painful procedures. this prospective, multicentric study focuses on the efficacy, safety and side effects of novalgin (metamizol sodium) for this indication. patients and method: novalgin was administered to children, aged between - years, with acute, postoperative or procedural pain. novalgin ( - mg/kg) was given - hourly iv or im respectively, in some cases ( ) in combination with opioids (tramadol , piritramid , butorphanol ). the pain relief was assessed by six-step verbal rating scale (vrs) from to , vital signs were monitored, the side effects, that occured were recorded. results: pain relief was good (vrs less ) in children - . % of study patients. novalgin was very well tolerated, only one patient had adverse reaction -hyperpyrexia following intravenous application of the drug. discussion: novalgin (metamizol sodium) is safe and effective drug in the management of acute pain in children with low incidence of side effects. obie~qve: a prostx~tive study comparing simultaneous, indepeadent ratings conducted by intensi~ sts using an american (comfort) and an european chartwig) sedation scale for mechanically ventilated pediatric patients. measurements and results: the study comprised observations in mechanically ventilated pediatric patients (aged days to years) in a pediatric intensive care unit (from march to january . each patient was sedated by his/her managing physician with opiates, benzodiazepines, barbiturates, used isolated or in combination. each observation consisted of a -mid period of oly~ervatien of the patient in his or her pediatric icu bed, after each observation, the comfort (analyses dimensional physiologic and behavioral subscores -range to paints) and hartwig (analyses dimensional behavioral subsenres -range to points) were performed by the intensivist. we established the comfort scores ~ correspanding to adequate (range to ), excessive (range to ), and inadequate (range to ) sedation; and, hartwlg scores z correslxmding to adequate (range to t ), excessive (range to , and inadequate (range to ). statistical mmlysisj: agreement rate (kappa) and p <. was considere d s!l~nificant. comfort ( . %) ( , %/ ( . %) hap, twig , ( . %) ( . %) ( . %) to the comfort score, the average for adequately sedated, inadequately sedated, and too sedated was . +- . , z _+ . , and a.+_l , respectively. and to the ha~twig scorn, the average for adequately sedated, inadequately sedated, and too sedated was . :k-' . , . -&l , and . l- . , respectively. conclnsion: in our study there were no significantly statistical difference when you apply a more complex scale (conff'ort) or a less complex scale (hartwig) to assess the sedation of mechanically vemilated pediatric patients. the application of local and intravenous morphine infusion after surgery of urinary tract eva nemeth , m.d. semmelweis medical university , first oepartment of paediatrics , budapest , hungary in±roduction:continuous analgesia with morphine may be ~egaroed as a safe and effective method of pain relief during postoperative period. subjects and methods: children /mean age . years/ underwent elective ureteroneoimplanta±ion were randomly selected to receive either morphin intravenously of lo ug/kg/h /group one/ or bladder morphineinfusion ug/kg/h /group two/ after surgery. all patients were prospectively evaluated during their s±ay in the postanaesthetic care unit. cardiac and respirafory rates,blood pressure,sa ~,degree of alertness,pain perception and complaints of the paticnto ~cr~ recorded hourly. pruritus,nausea and vomiting,voiding difficul-±ies,sedation,dysphoria were systematically sough and quoted. statistical analysis was performed by chi square test. results:postoperative analgesia was the same in the two groups,but side effects were less in the bladder morphine group,because of the lower se morphine concentration.the differentes weren't significant in two groups. conclusions:the administration of bladder morphine infusion is a safe and effective method in children. objetive: compare the evaluations of sedation level made by physicians and nurses with the visual analog scale (vas) and the comfort scale (cs) in pediatrics patients receiving difforents modes of intravenous sedation. material ~ method." file evaluations were made by an attending physician and nurse with the vas and by another physician (always the same) using the cs. the observations were divided following the sedation mode: one drug (fentanyl or midazolan), two continuous drugs, one continuous and one intermi~ent drug and two intermittent drug (fentanyl and midazolan). the groups were compared using the t-student test. the groups also were compared between the percentual of agreement of the evaluations of sedation level made by physicians and nurses with the cs and vas using the x . results: we didnk find any statistical difference between the observations made by physicians and nurses with the vas in the differmts modes of intravenous sedation, the average of the observations using the cs betwom one drug and two drugs modes didnk exhibit also statistical difference. the observations made by physicians mad nurses using the the vas when compared with the cs didn't show statistical difference between the sedation level. we found statistical difference only in percentual of concordance of sedation level between physicians and nurses when compared the one and two drugs modes of sedation. conclusion: we didn't find differences in the observations made by physicians and nurses in the sedation level, only in concordance pereentua/ of observations when compared two modes of sedation. the observations using the cs (more complex) didnk show differences when compared with the vas. effects of age, concurrent administration of other pharmacologic agents, and disease [cardiac(n= ) & pulmonary(n= )] on the pk & pd of b were evaluated in volume overloaded infants aged days- mo (n= ). single doses of . , . , . , . , . , , , . , . & . mg/kg iv were given over - min after baseline evaluation. age was used as a continuous vadable to determine its effects on the variability in the pk & pd of b. values for pk parameters were compared between patients in cardiac and pulmonary disease groups. hierarchical multiple regression analyses were used to determine the effects of age, disease and other pharmacologic agents on the variability of bumetanide excretion rate (ber) and pd responses, e.g. urine flow rate (ufr) & electrolyte excretion. cit, cir & cinr increased with age (p< . ) while t, decreased markedly in the first monthe of life (p< . ). ber normalized for dose increased with increasing age. patients with pulmonary disease exhibited significantly greater clearance and shorter t~= (p< . ) than those with cardiac disease whereas vd~ was similar in both groups. the administered dose of b was the primary determinant of ber but increasing age also contributed. penicillin antibiotics decreased ber. dose response curves for ufr and electrolyte excretion were similar between disease groups. more of the variability in ber and pd responses could be accounted for in the pulmonary group than the cardiac group but this was not statistically significant. conclusion: the pk of bumetanide were influenced significantly by age and disease. differences in pk between patients with pulmonary and cardiac disease were primarily due to differences in total clearance. age and the administered dose of b were positive determinants of ber and pd responses while penicillin antibiotics had a negative impact on both, once b reached its site of action, no differences in pd responses were detected between disease groups. the pharmacodynamic effects of bumetanide were evaluated in volume overloaded infants (n= ) aged days- months. single doses of . , . , . , . , , , . , . , . & . mg/kg iv were given over - rain. bumetanide concentration in blood (n=l ) & urine (n= ) samples were quantified by hplc. baseline urine samples were collected over - hours prior to drug administration. determinations of urine volume, electrolytes (na ", k +, ci, ca ++ and mg++), creatinine and osmolality were performed before and at - , - , - , - , - and - hours after bumetanide dosing. changes in urine flow rate and electrolyte excretion were plotted as a function of bumetanide excretion rate which was considered the effective dose of the drug. peak bumetanide excretion rate increased linearly with increasing doses of drug and showed no evidence of approaching a maximum. time course patterns for urine flow rate and electrolyte excretion were similar for all dosage groups. urine flow rate and electrolyte excretion increased lineady up to a bumetanide excretion rate of approximately #g/kg/hr and either plateaued (urine flow rate) or declined at bumetanide excretion rates > #g/kg/hr. bumetanide had no detectable effect on serum electrolyte concentrations, conclusion: maximal diuretic responses occurred at a bumetanide excretion rate of about ;~g/kg/hr. higher bumetanide excretion rates produced no increased diuretic effect. peak bumetanide excretion rate of about #g/kg/hr corresponded to bumetanide doses of . - . mg/kg. neonates using an electrical syringe-pump. authors: tr~luyer j.m., sertin a., bastard v., settegrana, c., bourget p., hubert p. background and objective: many problems can be observed with drug administration by i.v. route, especially in neonates. so we evaluate different protocols of teico delivery using an electrical syringe-pump. methods: we simulate infusion of teico with a syrlnge-pump (pilot c, becton & dickinson lab.) trough d standart neonatal i.v. system. for weights ( or kg) we used doses of teico ( mg and mg/kg) and a dose volume _< . ml. our goal was to perform a complete infusion in minutes. the infusion system consisted of an life care infusion pump (abbott lab.) with its lv. set for maintenance intravenous fluid (flow _< ml/h) connected to a -way stopcock. an meter extension tubing was placed between the stopcock and a neonatal catheter. an another meter tubing (injection tubing) connected the teicoplanine syringe to the stopc, ock. the volume of the injection circuit (from the syringe to the distal part of the catheter was . ml methods of injections were assessed: a: injection of the predetermined volume of teico in minutes with no wash out. b: idem as a but the teico was injected in minutes, followed by a wash out ( ml / minutes). c: twice the required volume was introduced in the syringe and the volume to infuse was programed in minutes, followed by a wash out ( ml/ minutes). d: ]dem as c but a priming was performed before connecting theteico syringe to the tubing. during each run, serial samples were collected every ten minutes over a one hour period. the samples were assessed using hplc method. results: the amount of drug delivred at minutes were calculated. the results are a mean of to runs and expressed as the percentage of the total amount of teico prescribed. a , % , % b % , % c a % , % d , % % conclusiom for accurate and reliable intermittent drug infusion with a syringe pump it is mandatory to use a precise protocol of administration and to take in account ) a priming (for immediate starting of infusion), ) a drug volume greater than the dose prescribed and a programmed volume injected, ) a wash out of the tubing (with a volume ~ , x volume of tubing injection) caz is an antibiotic with activity against the major pathogens responsible for neonatal bacterial infections. we previously reported the pharmacokinetics of caz in preterm infants on day of life which showed that the clearance of caz increased with increasing gestationat age (ga). mean serum half-life of infants with gas < wks was . h. we wanted to investigate the effect of postnatal age on caz pharmacokinetics, we therefore studied caz pharmacokinetics on day - of life in preterm infants with gas < wks. caz ( mg/kg) was administered as an intravenous bolus injection. blood samples were coilected before (t = ), and . , , , , and h after the caz dose and analyzed by hplcassay, the pharmacokinetics of caz followed a one-compartment open model. during newborns with complex congenital heart defects requiering either htx or palliative staged single ventricle repair were admitted to our hospital: hlh n= , unbalanced cavsd, tga with hypopl. rv and hypoplastic aoa. tga with hypopl. rv, sas and dextrocardia. /i children had been admitted with cardiogenic shuck and mukiorgan failure due to intermittend closure ofductus arteriosus; in / stabilization failed. parents were informed about the known and unknown risks of the always palliative surgery; in cases parents denied further therapy. one pafiem with hlh underwent orthotopic htx at the age of month after the ducms art. had been stunted in the newborn period. month later he is still in favourable condition and without any sign of acute organ rejection. / underwent first stage of palliative single ventricle repair: norwood -op. ( ) ( n= ), damus-kaye-stansel -procedure ( ). the clue to adequate postoperative management was to archieve a balanced distribution of flow to systemic and pulm circulation, that is to protect the single ventricle from volume overload and to guarantee sufficient oxygenation and pulmonary development as well. with the centralvenous sato at about % provided maintaining the arterial sato at about _+ % is corresponding with a qp/qs of : . using modified bt-shunts of . mm resp. a central anrtopulm, shunt of mm in one case l severe puim. hypertension, surgery at weeks of age ) there was no excessive pulm. blood flow and no need to increase pvr with inspired co . one child ( norwood at weeks, preexisting pnim_ edema ) developed severe pulur hypertension and parenchymal pulm. dysfunction after prolonged bypass and multiple transfusions due to intraoperative bleeding: hypoxemia could be managed successfully by implanting a second shunt of mm hh later and temporarily using prostacyclin and no; at sternum closure dd later the second shtmt was banded to ram. follow-up ranges - month: all children are at home being assigned for second stage operation at about month of age. establishing clinical practice guidelines has become increasingly important in the current health care environment. significant effort has been focused upon development of post-operetive critical care pathways. however, benchmark data upon which such pathways should be based has not been well reported. length of mechanical ventilation (lmv) and length of stay (los) for children following cardiac surgery, for example, is poorly described. we prospectively recorded the lmv and los in patients who underwent cardiothoracic surgery between / / to / / . only patients who belonged in any one of five categories of congenital heart disease (ventricular septal defect _+ other septal defects (vsd), atrioventricular (av) canal, tetralogy of fallot (tof), transposition of great arteries (tga), and single ventricle physiology (fontan)) were included. eight non-survivors were excluded from the analysis. all patients were admitted to an intensive care unit cu) post-operatively where mechanical ventilation was managed by pediatric intensivists. lmv was defined as the period from post-operative admission to planned extubation. length of stay (los) was defined to be from le from the icu. cytokine patterns during and after cardiac surgery in young children. especially in children, cardiac surgery with cardiopulmonary bypass (cpb) can cause a systemic inflammatory response. this process is thought to be mainly a result of inflammation induced by surgery and exposure of blood to an artificial surface, and of reperfusion injury during weaning of bypass. complement activation, degranulation of granulocytes, induction of free oxygen radicals, endotoxemia and release of cytokines, are important contributing factors. we studied cytokine patterns before, during and after cpb in young children admitted for complex surgery or for septal defect correction. in the first group, significant amounts of il- and il-lra could be detected preoperatively. these findings could reflect the already existing hemodynamic dysregutation. in both groups, cpb procedure upregulated the circulating pro-inflammatory cytokines il- / , but not il- b. at the same time, il-lra became detectable. therefore, we suggest that in these patients the production of the anti-inflammatory cytokine il-ira was not induced by the preceding acnvity ot pro-inflammatory cytoidnes. during cpb, we noticed a sharp decline in the capacity of the leucocytes to secrete il- / . the ex-vivo production of il-lra however, was only slightly attenuated. we conclude that there is a differential regulatory pathway for the induction of il- / and il-lra. in addition, we studied the influence of dexamethasone administration on the cytokine pattern. administration delayed the appearance of il- / and il-ira in the plasma, interestingly, it did only interfere with the ex-vivo production of pro-inflammatory cytokines. the latter supports our hypothesis that production of il- / and of il-lra is regulated by two independent pathways, ( %) of pts. % ofpts < months of age developed metabolic alkalosis as compared with % ofpts > months of age.the infants with metabolic alkalosis received more citrated blood products and furosemide. following cardiac pulmonary bypass the highest ph-values and be-values were observed - hours and - hours, respectively. ii. prospective study: metabolic alkalosis was registerd in t children ( %), of those < month ( %) developed metabolic alkalosis and % of those elder than monms.durmg the postoperative course patients younger than months developed the highest ph-and base excess values after and t hours, in the subset of the older patients maximum ph and base excess was found after and hours, respectively. in one case the top level ofph-value exceeded . , the base excess + mvalb. conclusion: children undergoing cardiac surgery with cardiopulmonary bypass often develop metabolic alkalosis.in contrast to previous reports, we did not observe an association between metabolic alkalosis and mortality, nor greater frequency of cardiac arrythmias or prolonged mechanical ventilation. in context with decreasing serum lactate levels, our data show positive correlation of metabolic alkalosis with postoperative improvement of liver function. respirator, mechanics and weaning outcome in children undergoing cardipvascular surgery. vassallo j., cernadas c., saporiti a., landry l., rivello g., buamsha d., rufach d., magliola r. mechanical ventilation (mv) and acute respiratory failure are common events in children unergolg cardiovascular surgery (cvs), the development of new techniques helped to measure some of the main respiratory mechanics (rm) in a non invasive fashion. our goal was to evaluate the predictive value of these measurements in weaning (w) outcome in these patients, patients and methods: we prospectively evaluated children considered clinically to be ready for w with < kg and > hs mv. patients with diaphragm paralysis and those who failed w because of upper airway obstruction were excluded. before patient extubation the following measurements were recorded during spontaneous ventilation (cpap/t piece) using the cp neonatal pulmonary monitor bicore (lrvine, ca): total respiratory system static compliance (cssr) and resistance (rts), rapid shallow breathing index (rsbi). maximal inspiratory negative pressure (pi max) was measured using an unidirectional expiratory valve. threshold values predicting w success (ws) were: cssr > . ml/cm h , rts < cm h /l/sec, rsbi and pi max > - cm t . w failures (wf) -patient reintubation within the following hs, these values were compared between w success and failures using fisher exact test. an apriori level of statistical significance was chosen at p < . . considered, an increase in tnf-a levels is observed after cardiac surgery (p< . ) with a return to previous values after hours (p< . ). hours after cpb, similar values are observed in groups ii and ill, but there is a further increase in serum tnf-a levels in group i when compared with both other groups (p< . ). we found no statistically differences in any other moment. there was a significant correlation between serum tnf-o levels determined hours after surgery and cpb duration (p< , ). conclusions: cpb in childhood provokes a significant increase in serum tnfa levels, in newborns the inflammatory response is maintained hours after surgery. this enhancement of serum tnf-e levels indicates the existence of a relevant inflammatory response in these patients. introduction: cardiac surgery appears to induce a systemic inflammatory response. we have investigated the behaviour of il- i~ and il- before and after cardiac surgery. patients and methods: we studied serum il- and il- levels from children with congenital heart disease ( boys and girls), aged from days to years, undergoing open heart surgery, before cpb (d we found no statistically differences in the il-i levels in the different groups and moments. there is a significant increase in il- immediately after surgery (p< , ) with similar levels hours after cpb and a significant decrease (p< . ) hours after cpb. preoperatory il- levels were higher in the groups i and tl than in group i (p< . ). hours after cpb serum il- levels in group were significantly higher when compared with group (p< . ). conclusions: cpb in childhood induces a significant transient increase in serum il- levels, strongly relevant in newborns. cpb was not associated to a significant modification in serum il- levels. thus, cpb in childhood induces a dissociated behaviour in the proinflammatory il- and il- & pathways. obiective, to evaluate the effects of amg receipt on the clinical condition during the first hours after birth (t ), the morbidity and mortality in immature outborn neonates. methods. we studied outborn neonates with ga to wks, admitted during the years to . eighteen neonates exposed to amg (ga: , +lwks, bw: _+ g) and neonates did not (ga: , _+ wks, bw: _+ g). results. amg-exposed neonates compared to those not exposed had lower incidence of apgar score at min _< ( % vs %, p<. ), lower incidence of ph t < . ( % vs %, p<. ), decrease need of bicarbonate ( % vs %, p<. ), lower fio (fio min> : % vs %, p<. and fio max > : % vs %, p<. ), lower incidence of intubation ( % vs %, p<. ), lower requirements of surfactant ( % vs %, p<. ) and lower mortality ( % vs % p<. ). there were no differences between the two groups for the following parameters: type of delivery, hypothermia hypoglycemia and anemia during admission, hypernatremia, hypotension (map< mmhg), need of dopamine and or plasma , incidences of ptx pda sepsis nec severe rop major ivh (plus pvl) and bpd and duration of intubation. conclusions. the main beneficial effects of amg receipt on the immature outborn neonates were the decrease of mortality and the decrease of surfactant need. there was no effect of amg receipt upon other severe morbidity in this high risk group of neonates. premature babies are very sensitive on homeostatic disturbances, and often develope intracranial haemorrhage (ich). ultrasound scan of the bram shows four grades of ich: -grade i -only periventricular hyperechogenic areas -grade ii -haemorrhage ham the lateral ventricles -grade ili-dilated lateral ventricles -gtrade iv -intracerebral haemorrhage. the purposes of this study were: to show the incidence of ich in premature babies and its correlation with the gestational age, . to determine the severity of ich . to present the outcome &those babies. in the study were included premature babies successively-born at the department of gynecology and obstetrics before gestational week (g.w.) and grouped in three groups: less than g.w., - g.w., - g.w. to all of them was performed ultrasound scan of the brain. results : . the incidence of ich hi premature babies is % and there is ingh level of correlation with the gestational age: -babies born before t~ g.w. have % incidence of ich and graduated : i grade - %, ii grade - %, iii grade - %, iv grade - % -babies old between - g.w. have incidence of % : i grade - %, i[ grade - %, iii grade - %. -babies older than g.w. have incidence of %: i grade - %, ii grade %, iii grade - % . sixty of premature babies have died and it is . % lethality. in all died ilffant was confirmed the grade of ich diagnosed by ultrasotmd scan of the brain. d. maksimo~ c. z.braiko~ic, n.vunjak. p. ivanovski ( ~iversi~, children's hospital. belgrade, yugosla~, ia infantile intracranial hemorrhage is the most frequent and serious manifestation of late hemorrhagic disease of the newborn caused by ,,~tamm k deficiency in earl?,, ti~fancy. in the last two years, we recorded five cases of infantile intracranial hemorrhage due to "dtamin k deficiency, despite routine prophylax~s (intramuscular vitamin k, mg) , with bpieal clinical presentation: age was - days (average days): vomiting, poor feeding, lethar~'irritabiljty, palor, bulging t ntanelle and convatsiones were present in most cases.two patients developed signs of hemorrhagic shock, with hemoglobin level less than g. . in ~ f \qi level was less than % of predicted value. there was no evidence of head trauma or liver disease in none of patients. four inlants were breast fed, while one, who had diarrheal disea.se, was on adapted milk formula. routine therapy wa.s given (including vitamin k and fresh frozen plasma). two patients were discharged with no sequellae, one developed posthemon'hagic hydrocephalus as a complication and two patients died. late hemorrhagic diseo.se of the newborn is sill/ a significant cause of morbidib' and mortality in earl ' infancy, despite different approaches to prophylaxis developed in recent years. background: neonatal hearing screening in at risk newborns can detect % of the children with a congenital hearing loss. automated abr hearing screening (algo- ) has been introduced for healthy newborns. the aim of this study is to test the validity of this algo- screener in at risk newborns in a neonatal intensive care unit. subjects: at risk newborns (median gest.age: . wks, median birthweight g) selected according to the criteria of the american joint committee on infant hearing. interventions: algo-i automated abr-hearing screening at a level of db was performed in the neonatal intensive care unit. when bilaterally referred, further audiologic screening and/or therapeutic intervention took place. when passed uni-or bilaterally, children enrolled in a) a nation wide screening programme (ewlng) at the age of months and b) in a half yearly follow-up programme in which hearing and speech-and language development were observed according to egan an illingworth. results: screening without disturbance from ambient noise or from routine technical equipment was possible in the incubator, even during nasal cpap therapy. ( %) newborns passed algo- screening. ( %) did not pass bilaterally. of with a congenital rubella died shortly after screening.in of bilateral congenital hearing loss of -> db was confirmed. of the newborns passed were still alive at the age of year. ewing screening was performed in of ( , %). / passed, of had passagere conductive hearing loss, in / no further investigation was performed. all children enrolled in the i/ yearly follow-up programme had normal speech-and language development. in this study all at risk newborns with bilateral congeni "tai hearing loss were detected with algo- screening. screening results showed no false negatives at follow-up. the algo- infant hearing screener can be used as an valid automated abr-screener to detect hearing loss in at risk newborns in a neonatal intensive care unit. gancia gp, bruschi l pnlito e, ferrari g, rondini g -divisione di patologia nc~matate e turapia intensiva -irccs policlinico s. mattco -pavia, italy latrogenic esophageal perforations (iep) in preterm and term infants are seldom reported in litteraturc, in association with difficult endotracheal (et) intubation (with or without stylets), insertion of gastric tube, and pharyngeal suctioning with stiff catheters. crieopharyngeal muscle spasm caused by instrumentation may also lead m a narrowing of lumen, with increased risk of local injury. we report iep observed in intubatcd, mechanically ventilated newborn infants ( male, female, all outborn). a common feature of iep was inability to pass a nasogastric (ng) tube into the stomach, mimicking e~)phageal atresia.~se : birth weight (bw) (i g, gestational age (ga) wk, sepsis. before admission to n cu, the baby underwent multiple et inmbations, because of inappropriate securing of et robe. bloody secretions in pharynx were observed. the endoscopy showed a large lesion at the end of proximal third of the esophagus, case : bw g, ga wk, rds. chest x-ray (cxr) showed a retrostcrnal air leak: the ng tube was stopped }~etwcen d and d and soluble contrast was seen in upper mediastinum.case : bw (/g, ga wk, rds. the endo~opy showed an esophageal lesion. cxr showed a paravertebral route of ng tube and a right pneumothorax.case : bw (i g, cz ,.v!:. rd c. ~!,'.::;;: ::':'_'rvt!~' s l" ~k':.rvrx. cwr, d,,,,vs ~,,mr~e, ~n rhe upper mediastinum and abnormal route of ng tube through a false passage. surgical intervention is needed in case of mediastinitis or mediastinal abscess: conservative management included broad spectrum antibiotics, total parenteral nutrition, antireflux therapy and, if necessary, drainage of air leaks. enteral feeding has been stopped lor days and cautiously resumed after radiographic study. [x~cal sequelae and death are uncommon, but iep occur in newborns with high risk of death due to prematurity and other diseases. in our patients, et intubation has been performed by experienced personnel: therefore the lack of skills in resu~itative procedures is not always the main factor of iep. prevention of iep requires appropriate materials (et tubes, laryngoscope blades, suction catheters), and procedures (positioning of the infant with correct neck estension, firm et placement). sedation and pain control may help to prevent the muscle spasm. aggressive treatment has improved the tong-term outcome of extremely low birth weight neonates (elbw) but it has also increased the chances of iatrogenic lesions. reviewing the charts of our neonates we observed a high number of vascular injuries. from to , neonates were admitted to the neonatal intensive care unit (nicu); of them were elbw ( . %). studying the charts of these elbw we observed cases ( m - f) with vascular lesions ( . %). mean gestational age of these patients was . weeks (rain -max ). mean weight at birth was g . mean weight at diagnosis was g ( - ). in the same period patients with vascular injuries were reported in the neonates over g ( . %). the injuries observed in elbw group were: arteriovenous fistula ( bilateral) at femoral,level, carotid lesion and limb ischemic lesions. aetiology was in cases by venipuncture, in one case umbilical catheter and in the case of carotid lesion a wrong surgical maneuver. no general simptoms were observed. the vessels were repaired with microsurgical technique in six cases: the carotid lesion and five arteriovenous fistula; one case was solved with thrombolitic drugs; an amputation at knee level was required in one case after a long period of medical treatment. the last neonate with an arteriovenous fistula was only observed for parent's will. at follow-up (clinical and by ecodoppler) out of neonates presented normal vascular function without sequelae. from our experience elbw neonates have more chances than older neonates to develop iatrogenic vascular lesions. we advocate an aggressive microsurgery and/or medical treatment to obtain good results and prevent late sequelae. a retrospective comparison between natural surfactants l.j.i.zimmermang m.c.m,van oosten. dept. pediatrics, div. neonatofogy, sophia children's hospital/erasmus university, rotterdam, the netherlands. aim: retrospective comparison of alvofact (in ) versus survanta (in ) as rescue treatment for neonatal respiratory distress syndrome (rds). methods: both surfactants were given at an initial dose of mg/kg (except for alvofact mg/kg for mild rds grade mi). repeat doses were attowed (survanta mg/kg, alvofact mg/kg) up to a maximum of mg/kg, all parameters and outcome criteria were strictly defined beforehand. the initial response (good,mild,no response,relapse) to surfactam therapy was defined on the basis of the decrease in fio . results: there were no signif. differences in patient population and initial parameters: ga ( . +_ . vs a _+ , wks), birth weight (t _+ vs -+ g), severity of rds (grade ill-iv: . % vs . %), apgar scores, cord blood gases, initial ventilatory settings. in ' however, the initial surfactant dose was administered earlier than in ' ( . -+ . vs . _+ . hrs postpartum, p= . ). although the average total cumulative dose was equal in ' and ' ( . -+ , vs . _+ . mg/kg), more doses of alvofact were given compared to survanta { . _+ . vs . _+ . , p=o.o ) and more patients in ' received more than two doses than in ' ( % vs % of patients). there was no difference in the incidence of non-putmonarycomplications. aivofact ( there was a better initial response to survanta and a better respiratory outcome in : in the group < g the duration of ventilation was half in , and in the group >~ og the duration of extra o need was half in as compared to . we speculate that the main reason for this difference is the earlier and initially higher dosing used with survanta compared to that used with alvofact which was given in the same total cumulative dose but over a larger time span. background: e×ogerlous sur&ct~t raplacem~t treatmem has become rou~ne k~ the t~eatme~t of respira~"¢ dim'~ syndrome (i~ds) of pr~e~tur~, wh~eas its effica w th odi~ respiratory diseoses is sdi being wader mvesugatio~. objective: "eac~ mt ereat isto report ottr results of prospect/re, non-randomized "re~-o.e" study oe suffact~t replacement in outhom premamae infa~t~ with rds reruirmg me~aical ventilatioa (nfv). p~tien~ and metho .s: from j-aly to june , / ; ( %) out~ ~¢ infaats, at a mesa age of z , horn's ( boys, ~rls; ~ gestafioan age -+ . weeks, mera~ birth weight _+ g, ~ . i" at minutes) with rds, requiring mv, received bov~e-suff~amt (survanta, ros~/aboti, laboratotie~ columbus, ohio) eadotracheally, as was recomm~aded by maaufacturer. as the c,~:ttrol group o~bom premature infants (ot~ of ; %, admitted with rds from euiy to eune ) were saelected ~d who did not receive surfaaam, compared with ~hctant ~'oup they were admitted for treatmeat e~'li~" aft~" daliv~:y (at the age . :: . hours vs. . +- hours), but they did not diff~ in othe~ baseline dam'a~eri~cs at ~ti~ion. entry crkeda for ~¢fa~aut ~hcadou were fractional i~firat o~ oxtgem r~emeats -fio > . - . , ratio au-lerlal to alveolar oxygea pre~are~ao ~ao < , ~ad oxyge~at,~ i~.dex -ol > . primary o~comes were deter~caned by ~hanges m exs'ge~ab, c~ ~r~d vmtilatic~ ~ the following variable~; ( ) fi'aaic~ of i~spired oxtge~ (fio ); ( ) mesa nnvay presmzre (map) ( ) pag ~ao ratio, ( ) oxyge~ion index (oi). commo~ comphcadces of prem,musty ~d con~ol mechamcal v~ati]al~on (pater dumas merios.s, intracr~nlal haemcrn:hage, air leak, br onchop ulmrmm'y dy~pl~a ~d death) were reg~ded as sec~d,~y outcomes. r~suas: in warfactaat group we observed slg~ .c~t improve~aeat (p< . ) in oxygea~thia md veaatilation at hours all~ e~try k~to the m~dy in compari~ion to nons~fa~m" group. compa~on of secondao' outcomes in ~ts with p,.ds showes table l we did not observe ~y major acute hfe fl:u-eattming complicatlola,s m sxlrlhct~mt grou~ tr/lmediately after stu'~actsmt rcplacemev_t therapy. the duramm of mechmucal ven~ation ~ad oxygen lreau~ent m survivals of both groups did not dafter gmficautl y a-ore ead~ other. condusion: l!a premature mthats with rds treated with surfaaaat replacemeaat therapy we observed decrease m mc~de~ce of tme'~m~o~oraces add de~th (p< . and p< . ), whe~e~s m othe~ observed variables thee was uo ,igmfi~t d~=ecce infectious complications during the therapy of respiratory insufficiency in neonates with birth weight less than g in the course of yearsretrospective study. zitek infants on cmv, cppv, and imv were administered exosurf in dose of - mg/kg twice endotracheally (see table) . in newborns ( . %) hours after surfactant admin fi value decreased by . %, and after hours -by . % compared with initial value; pip and peep values decreased by - cm h and - cm h after hours, and by - cm h and - cm h after day, respectively accompanied by mean decrease of aado from , to . mmhg, qs/qt decrease from . to . % (see table) . mean time of cmv, cppv was . days, imv- - hours, cpap - - hours. respiratory therapy in newborns ( . %) was complicated by pneumothorax (bilateral -in infants chorioangioma is a rela~ively rare placentai malformation associated with considerable mortality and morbidity. a chorioangioma can be regarded as an arterio-venous shunt in the circulatory system of the fetus. this causes volume loading eventually resulting in cardiomegaly and high output cardiac failure. a female neonate (gest age wk, birth weight g, - . sd) was born with an apgar score of and after and rain respectively. the placenta showed multiple chorioangioma. ultrasound of the heart showed a hypertrophic cardiomyopathy. she developed severe hypertension ( / mm hg), treated with nitroglycerine and nitropruside. finally blood pressure decreased when enalaprillic acid was given ( . mg.kg ). we measuered the activity of the renin-angiotensinsystem. an elevation in renin-angiotensin system is shown probably to compensate for the low resistance circulation before birth, hypothesis: the instantaneous cut off of a large arteriovenous shunt did not result in a fast downregulation of the renin-angiotensin system resulting in hypertension. hypertension should be added to the list of complications of chorioangioma of the placenta. the authors studied cases of children's septicemia with blood culture yielding staphylocucetts aurens. the age of patients varied from months to years ( , % from years downward), % of the children caught their disease in the hot season (may to october). the deaths also occured in this season: , % ( / ). following were the anatomo-dinical lesions. -skin %, muscle , %, bone , %, joint . %. -viscera : lung %, heart . %, cerebrum . %, kidney . %, fiver , %. -simple lesion skin-muscle-bone joint: %, no death in this group. the concomitant lesions of the soft tissue,bone-joint and viscera : % with one viscera, % with two viscera, % with three viscera and % with four viscera. -bone lesion : mainly on the long bones ( % on the tibia, % on the femur, the remainder being the mandible ( ) and the humerus), inflammation of' the hip joint was the main one. -i,ung lesion had forms pneumatocele ( cases), bronchopneumonia ( cases), pleural effusion ( cases), multimicroabcess bursting into the pleura ( cases), most multimicroabcesses were lethal : / ( , %), -heart: all thethreelay~rs got le@~r~, % had or layers alrected and death ensued. -cerebrum : the meninges had three forms of lesions purulent meningitis ( cases), obturafing embolns of brain vessels ( cases) and cerebral abcess (one case). the characteristic clinical sign was paralysis and meningismus, phlebothrombosis of eavcrnous finus ( cases)was mually ther~sultofalxil vdfi:h burst there were cases of death with lesion of the meninges and cases of obturating embolns of brain vessels. -the main sign of lesion of the kidney was a change in the components of urine: % got proteinuria, % had leucocytes in their urine, % had erythrocytes in their urine, the urea in their blood increased (over rag%) in . % of cases.the lesion of the kidney seemingly had little relation to death. seven cases of ictertts due to an increase of direct bilirubinemia and a decrease of blood-albumin. -the biological characteristics of the pathogen staphylococci showed that all the isolated specimens had positive coagulaza ; the specimens from the dead patients were less semiti~e to, mad ~t to mali~ overag death rate was . % ( / ). the fungal infection to fusariun species in immunocompromissed child have been reported in the literature with a rare, severe and high, mortality rate in spite.of the use of antifungal drugs. we report a case of successful treatment of a severe disseminated fusariun infection in a ll-year-old boy with acute lymphocytic leukemia (lla-l ), after use a chemotherapy followed by absolute granuloeytopenia. the patient developed fever, skin lesions, pneumonia and fungaemia. fusariun species was cultured from the blood, necrotic skin lesions and lung secretion. the child developed multiple organ system disfunctiou in spite of use broad spectrum antibiotcs and antimycotic therapy needing. uci during days. the patient receive suport treatment (mechanical ventilation, inotropie d~.ugs, diuretics, imunestimulants, blood components, a broad spectrum antibiotes and antifungal agents). we absorved a gradual recovery in the white blood cell count and regression on the sites of infection. the association of preeoce diagnostic and the terapentic with increase in the white blood cell count was the most important in a successful treatment. a year old african-american child suffered a severe pulmonary injury in a house fire. initial survey revealed % total body surface burns, soot on the face, and bloody endotracheal secretions. initial chest radiograph revealed diffuse, bilateral infiltrates. severe respiratory failure with an oxygenation ratio of rapidly developed. he developed a pneumomediastinum and subcutaneous emphysema. although transient improvement occurred with inverse i:e ventilation and surfactant, he became more hypoxic (sac as low as %) and acidotic. on day post injury, he was placed on venc~venous extracorporeal life support (ecls). on ecls day he was decannulated. chest radiograph on ecls day showed an opacity in the left chest. ultrasound of the left chest was consistent with atelectasis rather than pleural fluid. flexible bronchoseopy failed to reveal any obstruction in the left lung. a computed tomography (ct) seen of the chest, which was performed after decannulation, revealed a large loculated collection of fluid in the left, anterior chest. under ct guidance, a f cope loop catheter was inserted and cc of thick blood was removed, follow-up ct performed immediately after this procedure revealed minimal change in the size of the fluid cavity. over the next hr, we instilled urokinase , units over minutes every two hours. a minute dwell time was allowed before draining the fluid. repeat ct scan done at the end of the urokinase infusion showed a marked decrease in the size of the fluid cavity. act scan was not performed prior to decarmulation because the ecls circuit tubing was too short to allow appropriate positioning of the child in the ct scanner. after a ct scan revealed loculated pleural fluid, a simple drainage procedure was diagnostic but inadequate treatment. we were able to successfully dissolve the thrombus after hr of urokinase therapy even though the thrombus was > days old. we suggest that large loculated plenral thrombi which develop as a complication of ecls therapy may be successfully managed with urokinase infusion. introduction: haemorrhages, particularly intracranial, are major complications experienced in - % of neonates treated with extracorporeal circulation. an induced thrombocytopenia and impaired platelet function play a key role in the increased bleeding tendency observed in these patients. the aim of the present study was to establish a dose-respons curve for the effect of a synthetic protease inhibiting agent, nafamostat mesilate (fut- ), on platelet membrane glycoprotein density and platelet activation during experimental perfusion. methods: two identical extracorporeal life support (ecls) circuits were primed with fresh, heparinized human blood and circulated for h. four different concentrations of fut- ( . mg/l blood/h; . mg/l/h; . mg/l/h+ % bolus at the start of the perfusion and & mg/l/h+ % bolus) were used in different perfusion experiments. a total of eight paired experiments were performed. platelet count, plasma betathromboglobulin levels and platelet membrane density of glycoprotein ib and lib/ilia were followed as well as plasma concentration of haemoglobin. results: a protective effect of the agent on platelet count, plasma concentration of btg and platelet membrane gpib could be observed during the first hours of the perfusion when a bolus dose was added. no positive effect could be recorded with the two lower doses used. plasma concentration of haemoglobin was higher in all the fut-circuits compared to the control circuits. conclusion: the addition of a bolus dose of fut- at the start of the perfusion seem to induce a protective effect on platelets during the first hours of perfusion. extracorporeal membrane oxygenation (emco) is a form of invasive cardiopulmonary support that can provide imporary physiologic stabilisation in reversible circulatory failure and or respiratory failure. we reviewed our expierence with extra corporeal membrane oxygenetion in children aged day to year between and . two neonates was succesfully decanulated, but died - well after decanulation due to septic complictions. one child years old, one neonates died on day and day" respectively while still on emco. complication which were and encountered were heavy bleeding in case (child), (neonate) and raceway rupture in case (neonate). problems which are specific developing countries like indonisia are: high cost ( . us for days) difficulty in transportation (transporting intubated baby) from the orgin hospital, lack of knowledge and understanding of the primary physician and nm-ses and difficulty organizing in hours emco team. resnratory mon tor/ng in picu z,zjvkovic, s. mihailovic, o, tosev respiratory monitoring in pediatric intensive care unit picu) provide the importartt informations for understanding of the pathophysiology of the clinical signs, aid with the diagnosis, and assist in therapeutic management and predicting prognosis. pien in children's hospital for ~flmonary diseases and tuberentosis remained for the t~s't two end a half years relatively limited for diagnomic tools and therapeutic regimens, mostly because of the poor fmnaeial suptx~rt. the number of children admitted for aurae asthmatic at.lzek~ severe pneumonias, bronehiolitis, complicated pulmonary tuberculosis, foreign bodies and exacerbations of ehronit'. pulatonary diseases was t . for all patients the respirator' monitoring system means: physie~d examination, ehe~ x rays, capillary bltxxl gas mmlyses (vevv few ehiktren experienced itwasive arterial blt~.~'i gases), noninvasive oxyntctry, measuring of the vital capacity in coopo-able patients, as~d capnography. later on, after the imtial critical illness, a complete hmg fimction tests was performed, as well ,~s bronehoscopy in selected eases, (~lr experience revealed that abotrt % of ehil&en heos suecessthl outcome, without s~lllens , instead they had been tremted in limited conditions. ']'he rest of our patients were previously diagnosed ~s ettronie pulmonary patients, with high risk score system ibr having seqnells 'llae mortality rate were , %. the continuous blood gas monitor, pasatrend (biomedical sensors, ltd., high wycombe, bucks, england) has the capability of measuring ph, pco , and po via an indwelling optical absorption optodelclark electrode sensor that is placed through an intra-arterial catheter. we evaluated the accuracy of the sensor in radial and femoral locations in critically ill pediatric patients. methods: the simultaneous values of ph, pcoz, and po recorded from the paratrend monitor were compared to values measured by standard arterial blood gas analyzer (coming , ciba-corning diagnostics, medfield, ma). criteria for the elimination of data points included a core vs. sensor temp. gradient, and sensor pulled back beyond accepted insertion distance. mean time of monitoring per sensor was hours (range . - . hrs). mean time of radial monitoring was hrs (range . - . hrs) and of femoral monitoring was . hrs (range . - . hrs.). linear regression and bland-altman analysis for bias and precision for each parameter were calculated. results: a total of patients (age range weeks to years) had paired samples of ph, pens, and poz made by the sensor and blood g&s analyzer. the range of measurements were ph . - . , pco, . -i . t(n r, and po - torr. the paratrend monitor demonstrated accuracy that is comparable to the accepted standard of blood gas analysis in a group of critically ill pediatric patients manifesting wide variation in ph, pen , and poz..this technique appears m be very useful especially in the extreme values of the parameters measured. funding provided by biomedical sensors. understanding of pulse oximetry d.semple, l.e.wilson. royal hospital for sick children, edinburgh, eh lf, scotland, uk. pulse oximetry is a useful, non-invasive monitor, routinely used on the itu and increasingly often on the general wards. we used a questionnaire incorporating questions on the theory and clinical uses of the pulse oximeter to assess understanding of pulse oximetry in medical and paramedical staff doctors indicated grade, speciality, pulse oximetry tuition and neonatology experience. doctors, itu nurses, t medical students and physiotherapists completed the questionnaire. some confusion existed between the principles of pulse oximetry and transcutaneous oxygen measurement. wide variations in the lowest acceptable saturation in fit children were seen ( - %), with around % of respondents in all groups accepting values of % or less. some potentially serious mistakes were made in the evaluation of oxygen saturations in the clinical scenarios. there were widespread variations in correct responses at all grades of medical staffing. nurses scored well on more clinically-orientated questions but relatively poorly on theory. only % of doctors (mostly senior grades) had received tuition in putse oximetry. neonatology rotations appeared to confer little additional knowledge on pulse oximetry. few doctors and nurses receive tuition in the use of pulse oximetry a significant proportion of nurses and doctors, of all grades, exhibited a lack o{" understanding of the principles of pulse oximetry. this may result in unsafe use of the equipment and put patients at risk. one can see from the table that blood composition in uv and ua differens in some characteristics, and similar in sgp magnitude. venous-asterlal gradients "gas functiomals" between uv and ua represent the measure of difference in this characteristics. the gradient cari be positive, zero -order or negative and change both in value and in sign but not reach apo (positive) and apco (negative) in absolute significance.minimization of "gas functionals" deviations atom the zero is achieved due to"mutual replacement acts" between po and pco in uv and ua blood. we suggest that presented tests can be useful in full evaluation of gas exchange in newborns. (pap) in the context of pulmonary hypertension is oft desired but rarely achieved. inhaled nitric oxide (no) has been shown to produce this desirable effect, but is relatively difficult to administer or monitor. we wondered whether np, chemicaily related to no but more stable in solution, would produce similar physiologic effects when administered in the convenient modality of nebulization. methods: piglets were anesthetized, mechanically ventilated, and surgically instrumented. systemic blood pressure (bp), pap, and cardiac output (co) were monitored continuously. after postoperative stabilization, . % nac} nebulization was begun, and pulmonary hypertensiorr was induced by reducing fio from . to . . the piglets were monitored for minutes during this hypoxic phase, next, without altering fio or ventilator settings, np ( mg/ml, dissolved in . % nacl, flow ipm) was substitued for . % nacl in the nebulizer circuit. np was nebulized for mins. results: during hypoxia, pao fell from to mm hg. pap rose during hypoxia from to torr (p< . ). ,^fhile bp and co did not change significantly. pap fell during nebulized np in each piglet, (mean apap = to torr; p< . ; mean reduction of hypoxia-induced rise in pap = %; range: to %; p < . ). pvr/svr fell by % during np nebulization (p< . ), while bp and co did not fall significantly ( to tort; to mllkg-min), the reduction in pap began within minutes of the onset of nebulized np, and appeared to reach a plateau by minutes. no tachyphylaxis to nebulized np was noted. nebulized np did not significantly affect pap, bp, or co under normoxic conditions. conclusions: ) like no, np selectively reduced hypoxia-induced pulmonary hypertension without altering systemic bp, ) unlike no, np can be administered by nebulizer, a technique familiar to virtually all health-care providers, and potentially adaptable to both intubated and non-intubated patients. } nebulized np may be beneficial in clinical contexts where inhaled no is impractical. dang phuong kiet and nguyen xuan thu examining cases of purulent pericarditis with various clinical forms treated by surgery, the authors drew the following experiences for their diagnosis. t. clinical factors. purulent pericarditis appeared like a cardiac tamponade in a septicemia due to staphylococci with dassieal symptoms: severe dyspnea, tachycardia, faint heartsound, big liver, prominent cervical vein ; rentgenography of the chest showing enlargement of the cardiac silhouette, a diminution of ventricular pulsations, ~i clear lung field. by an emergency operation, ml of diluted blood were drained. purulent pericarditis and pleural effusion appeared at the same time but at first tile symptoms of purulent pericarditis were masked by the predominant symptoms of plearal efihsion. after the pleura was drained, its pus was no more, the general state was relatively stabilized but there still were big liver, dyspnea, enlargement of the cardiac silhouette while central venous pressure increased. purulent pericarditis appeared late. in the first stage (about weeks) there was no suspected sign. later on gradually appeared such symptoms as dyspnea (during serum transfusion for instance). central veinous pressure also raised. the heart chest diametre increased at first (up to - %) then decreased (down to below % ) but the liver kept on swelling together with the particular changes of electroeaediegramme. now the pericardium had no more pus but get fibrous (up to ram) thus constricting the heart and its main arteries ike pick syndrome). . diagnostic values of electrocardiograms : common signs of ecg related of these purulent pericarditis were: a diminution of voltage, a widespread elevation of the st segment, the tf wave flattened and inverted. however, what should be stressed was : the diagnostic values of an electrocardiogram for purulent pericarditis was mainly in the dynamics of their signs: in the first week, the voltage diminished corresponding to a pericardium containing pus, while the st segment went up then seemed parallel to the fibrosis of the epicardium, the liver swelled, the central velnous pressure increased, the heart/chest dimension ratio decreased, the st segment went down, the t wave became more flat and inverted. between and neonates, aged - days (median ), weight , - kg (median , ) with critical valvar pulmonary stenosis were scheduled for balloon dilation (psvp), children ( %) were on pge and ( %) needed mechanical ventilation. after stepwise dilation a final balloon : pulmonary valve (pav) ratio of % ( - ) was achieved, there was a significant correlation (p< , ) between an adequately sized balloon and freedom of reintervention. two valves could not be passed, four neonates underwent surgical procedures (brock n = , commissurotomy n = ), two children ( %) died of sepsis. / patients ( %) were successfully palliated by psvp in the first month of life. the rv : systemic pressure value fell from % ( - ) to % ( - ), complications included transient dysrhythmias, transient hypoxia, vessel occlusions;- right ventricular outflow tract perforation. in / patients follow up data is available. the residual systolic peak doppler gradient over the pav on the last out patient visit ( - months after psvp) was - mmhg (median ). four children needed repea.ted psvp to months after the initial intervention. conclusion: psvp of critically ill newborns is possible. the risk of mortality is relatively low. psvp in neonates with an adequately sized balloon is a challenging alternative to surgical treatment. post hypoxic-ischemic (hi) reperfusion induces the formation of non protein bound iron (npbi), leading to production of the reactive hydroxyl radical. it was investigated if the ironchelator deferoxamine (dfo) could reduce free radical production and improve neonatal myocardial performance after hi. severe hi was produced in newborn lambs and changes from pre-hl values were measured at , and min post-hi for (mean) aortic pressure (mean pao), cardiac output (co) and stroke work (sw). left ventricular (lv) contractility and co were assessed by measuring lv pressure (tip-manometer) and volume (conductance catheter), using inferior caval vein occlusion to obtain slope (ees) and intercept of the end systolic pv relationship (v ). npbi, reduced and oxidized vitamine c ratio (vcred/ox) and lipid peroxidation (mda) were measured from sinus coronarius blood. lambs received dfo ( mg/kg i.v.) immediately post-hi, control lambs (cont) received a placebo. results: mean pao was stable, co and sw decreased up to and % respectively in cont as compared to pre-hi. in both dfo-groups co and sw remained within the normal range. ees and v decreased in all groups post hi, but did not differ between groups. npbi and mda were higher at min post hi (p<o. ), vcred/ox was lower at min post-hi (p<o.o ) in cont as compared to dfo-group, indicating more oxidative stress in cont. conclusions: dfo reduced the oxidative stress of the heart and prevented co and sw to drop, suggesting a positive effect of iron chelation on the myocardium after h{. from we published reports with analysis of performance of the heart as a whole organ.while analysing the heart performance as a whole, we recognize three block in it located intrapericardially: l."atrial"block -left (la) and rigth (ra) atriums; ."aorta-pulmonary" block-aorta 'bulb (a) and pulmonary artery(pa); .ventricular "three-chambered" block (vb) consisting of: -left (lv) and right (rv) myocardial chambers, both frith blood outflow into "aorta-pulmonary" block vessels, and -spongy (venous) myocardial chamber with the blood outflow through coronary sinus (cs) and thebesiau vein (tv) into "atrial" block. the following conceps are introduced for vb functions assessment "common" systole and "common" diastole of "three-chambered" vb. the process of normal "common" vb systole: -begins with blood ejection from vb spongy chamber into the "atrial" block; -continues with blood outflow from rv and lv into "aorta-pulmonary" block wi~ venous minimums -x-coiiapses -~btmation iu "a~riai" block; -completes with "three-chambered" vb general emptying. at this period the following blood volumes are transferring: -two-from rv and lv(their stroke volumes)into"aor~o-pulmonary"block; -two-from "spongy" chamber .into "atrial" block; -two-from systemic and pulmonary veins into "atrial" block during the process of so called "systolic" membrane suction (at pulling atrio-ventricular valves into rv and lv chambers as blood ejects out of them). it appears to be the regulation of blood inflow to "atrial" block by blond outflow from "three-chambered" vb into "aorto-pulmonary" block. objective: to evaluate the efficacy and complications of transpyloric enteral nutrition(ten) in critically ill children patients and methods~ from june to january children (i boys and girls), aged from days to years (mean l. ± . years) were treated with ten. patients were included after cardiac surgery, with acute respiratory failure, and after cerebral surgery. the indication of ten was mechanical ventilation in patients and failure of nasogastric nutrition in patient. children ( %) had previously received parenteral nutrition. and i fg enteral tubes was inserted into duodenus through nasogastric intubation en patients and by endoscopy in patients. rx and ph determination were used as methods to control tube situation. children received adapted formula, caseine hidrolisate, and enteral formulas. (in patients the nutrition formula was changed during ten). patients were supported with mechanical ventilation during ten, received midazolamperfussion(range to mcg/kg/min), fentanyl (i - . mcg/kg/h), and vecuronium ( . - . mg/kg/h). resulte: ten was used during to days (mean . ± . days). mean maximmnvolume ad~iniateredwas ± ml/kg/day (range ) .patients with midazolam, fentanyl and vecuronitml tolerated ten similar than children without sedatives. complications were diarrhoea patient, abdominal distension and/or important gastric fed residuals patients. pulmonary aspiration or respiratory complications were no registered. ten was ended in one patient due to diarrhoea, in due to change to oral or nasogastric nutrition, children continue yet with ten and was discharged of picuwith ten. conolusion: ten is an useful method of nutritional support in critically ill children with mechanical ventilation and/or nasogastric intolerance. introduction: the enteral nutritional support of the critically ill child may reduce the morbidity and mortality by attenuating, the hypermetabolic and catabolic response, decreasing the gut translocation and the septic complications, improving the bowel mucosa integrity and the wound healing. the aim of this study was to show the safety and tolerance of en. methods: we enrolled consecutive patients admitted to our unit from may to december , mean age . years (range imonth to i years). the prism, mechanical ventilation, inotropic use, opiates and other drugs were recorded. the en was delivered by continuous infusion across a polyuretane tube.we kept the patients head elevated °, and we used cisapride routinely. the gap betweeen admission and the en beginning, average time to meet the nutritional objective, en duration, selected formula, patients outcome and complications were recorded. results: prism groups were - = patients; - = ; - = ; - = ; - = . two patients with mof (multiorgan failure) died. % needed mechanical ventilation.the average time elapsed from picu admission to initiation of en was . days (range to ) and the average duration of the en was . days (range to t ). the average time to meet the nutritional objective was days (range to ). the selected formula were: lactose free infant formula in patients, elemental diet in , pediasure in and jevity in . we recorded vomiting in patients, diarrhea in and constipation in . none of them forced the en suspension. we didn't recorded any case of ~spiration or pneumonia. we found no relation between drugs, selected formula and complications. we think that en may be a safe and well tolerated procedure at the picu setting. generation of free radicals in iipid emulsions used in parenterai nutrition (pn) has been described recently. this seems to be due to high polyunsaturated fatty acid content. we studied lipoperoxidation status and antioxidant parameters presurgically and through the postoperative period ( days) in a group of twelve children (ranging from months to years of age), who underwent heart surgery and received nutritional support with pn. malondiaidehyde (mda), an end product of lipid peroxidation was used as a marker of oxidative stress. it was determined by the yagi spectrofluorometric method. antioxidant activity was measured with an assay based on the inhibition of spontaneous autooxidation of a brain homogenate, and vitamin e in serum by the technique of hansen and warick. erythrocyte mda release fonowing incubation in hzo in vitro was used as a functional measure of tissue vitamin e levels. data were compared using one-way variance analysis. there was not significant differences in the plasma mda production among the values obtained before surgery ( :t: . nmol/ml), postoperative pre-pn ( . +_ . nmol/ml) and through the course of pn ( . : . nmol/ml). levels of vitamin e previous to surgery were , : . #g/ml and decreased to . _+ . #g/ml at hours post-surgery before starting pn. while receiving pn, concentrations of vitamin e increased progressively up to + . l #g/ml (p = . ). pre-surgicai plasma antioxidaut activity values ( :i: %) dimiuished in the first postoperative day ( _+ . %) and then showed a clear increasing tendency, directly correlated with that observed in vitamin e levels. the measurements of the maximal percentage of mda release of erythrocytes in vitro, showed an inverse relationship with plasma vitamin e levels and with the plasma antioxidant capacity: preoperative . + . % and postoperative descending from . + % to _+ . %. our results indicate that during surgery and within hours postsurgery, a decline in antioxidant defenses occurs, in the postoperative period, while patients are on pn and taldng into account our obtained data: the unaltered mda values, the rise of plasma vitamin e levels, the recovery of both functional erythrocyte membrane antioxidant protection and the plasma antioxidant activity, they do reflect that during the intravenous administration of lipid infusions, oxidative damage does not occur, probably due to the addition of vitamin e to pn solutions in order to avoid autooxidation of lipid emulsions. garnitine is one of the essential nutrient in the diet of newborn infants. mother's milk represents the natural eamitine source for the newborn infants. we studied enteral earnitine intake in premature infants eutrophic (eu) and hypotrophic (hy), fed with mothers milk trough consecutive days-from fifth to tenth day of life. mean gestational age was (range - ) weeks for eu and (range - ) weeks for hy. birth weight was ranged - g for eu and - g for hy (p < , ). breast milk carnitine concentration was , i.tmol/i in mothers milk delivered eutrophic babies, and singnificant higher mean coenetration , l.tmol/i, of hypotrophic premature infants (p< , ). breast milk earnitine concentration was ranged between , - , ~moi,'l, and daily carnitine excretion was between , - , p.mol/i, mean , +- , i p.molll. the daily mean carnitine intake was from - , mgkg/d, in eutrophic and , - , mg/kg/d, in hypotrophic premature infants, in milk volumene intake from - mllkgld., the results of this study suggest that premature infants should be fed with own mothers mitk in eady neonatal pedod in attempt to prevent camitine deficiency. keto-acids and parenteral lipid admlnistration. castorina m., antuzzi d., ricci r., rendeli c., polidori g. pediatric intensive care unit -catholic university -roma (italy). some metabolic studies have suggested that the administration of mediumchain tltgticerides (mct) might induce a marked increase in ketone body concentrations; the aim of this study is to evaluate the effective ketogenetic risk of infusing mct emulsions in total parenteral nutrition (tpn). two groups of seriously infected children were examined: a- septic infants were given to tpn with a % of long-chain tryglicerides ( lct). b- septic infants, in wich the lipid source in tpn consisted in a - mixture of lct and mct. the children in the different groups showed similar severity and therapeutic scores (prism, tiss, ~, f~ , f~ ); the lipid intake was the same, corresponding to - . g, ckg bodyweight/day. in all patients a sample of urine was taken six times a day for the whole time of tpn the urine samples were screened by the diphenylhydrazone test, and the ketoacids excretion was confirmed by a chromatography. the urinary excretion of -keto-acids equivalent to p-ohphenyl-pymvate (mcg/ml urine) is summarized in the no significant increases in frequence and/or in severity of acid-base disturbances were found in all studied patients in consequence of the lipid infusion. the patients of b-group showed a lower excretion of -ketoacids. the c~-keto-acids excretion was ever unsignificant and seemed to be correlated with the illness severity more than with the lenght of the tryglicerides chain. this observations let us suppose that the mct, at employed doses, can be safely administred also in childen with metabolic acidosis and/or serious illness. reye syndrome cayetano heredia hospital, lima, peru five patients with reye syndrome were studied; included were those diagnosed from january to march and treated at cayetano heredia hospital. the age of presentation varied from z. to months. the syndrome occurred more frequently in males ( / ); the time of illness at the presentation varied from to lo days, and the following features were found: fever ( / ), akeration in mental status ( / ), seizures ( / ), gastrointestinal illnesses (diarrhea) ( / ), and respiratory insufficiency ( / ) --in this case ventilator)-support was needed, in all cases hepatomegaly, intracranial hypertension, hypokalemia hyponatremia, metabolic acidosis, hyperammonemia and elevation of hepatic enzymes were found. coagulation blood tests were abnormal in three patients. cerebrospinal fluid (csf) showed hypocellularity in all cases (less than cells/ram ). the cultives were negative, and the final diagnosis was confirmed by hepatic biopsy. no deaths were due to reye syndrome. a contribuhon to the study of reye's syndrome the aulhors analysed records of patients meeting all the clinical, biochemical and anatomic criteria put forward by hutrealoch~ and samaha ( ) who were ireated at the emergency and resusdlation depammlt tithe ipch in years. the average age of the children was years (the ~umgest monks and the driest year~ most of lhon ( / ) came from lhe countryside to lhe lmfia~ willfin hours of file oulbreak. a few days previously the patients w¢~ld have fever (some of ahem wilh diarrhea or cough) ,,rod vomit then rapidly fidl into coma and c~nvuksien. they ~me to the imtia~ with the signs of typical increased inlracranial pressure ( stages - according to lovejiy for most cases) but the liver was unllkely big. the main biocheafical dmnge of the blood was acute hepatic thilure -the bllod glucose decreased : (ha the aver~ , n~% ( ) ~ not measured in five cases (glucose a"aces). -the blood ammonia ino~ased riven to microg/dl fin lhe average , n = ) -the percentage of p~in was low, in the average , % (n-- ), % at the lowest (a case ofmekaa lasling five days was ctwed with vitamin k). -got and gpt enzymes increased - times (n= ) besides, tht~re was decompcmated addt~is with lhe average valnes ph = . ; pcoz = ~ mmhg and eli = - ~ ~, (n~). the charadaislic dumge in the ¢~'ebrospinal fluid was a low glucose tx~acenwalien h the average of k mg/dl ( cases of glucose it'aces) ; meanwhile protein decreased in the average of mg/dl ( cases below mg/dl). besides ~here was no inflammatory lesion ~tion) : very serious brain oedona and fatty degeneration of live~ scatteredly or parllally.microso~ically (biopsy and necropsy) in file brain appeared bright space around blood arteries and glioma extended v'lrdmw -robin space, with no inflammatory reaction. liver.-the sa~dure was intact there was no " "mtlammal~s ' cell, the kupffer cells did not show hyperplasia but show a heterogenous deg~nerafion~eart: also showed a fatty degencralion in some areas of the myocard eellkidney: the ihtty degenerati~l scattetedly in the tubular cell. pano~as:fatty degeneration scattetedly in file pancreatic cell. two cases of liver biopsy for lhe rid lime (check before leaving file inslitute) found that fatty degeneration was r~tta~ nearty ff~pletely. the exact muse remained unknown. objectives: to analyse whether there exists serum and urine electrolyte disorder in children with respiratory failure, methods: we have made prospective study of children in our icu during a month period, electrolyte concentrations were measured in serum and urine collected during hours (sodium-na, potassium k, chloride-ci, calcium-ca, magnesium-mg and phosphorus-p). results: average values in serum were: na . +/- , (rv: - ) mmol/i, k . +/- . ( . - . )mmol/i), cl . +/- . ( - ) mmol/l, ca .t +/- . ( . . )mm /i), mg . +/- . ( . - . )mmol/i. average electrolyte levels in hours urine were: na . ~/~ . ( - )mmol/day. k . +/- . ( - )mmol/day, ci . +/- . ( - )mmol/day, ca . +/- . ( . - . )mmol/day and p . +/- . ( . - )mmol/day. conclusions: average serum ci and ca levels were decreased in children with respiratory failure. in urine, average k, ci, ca and mg levels were decreased and urine p concentration was increased. we concluded that serum and urine electrolite disbalance may be expected in children with respiratory failure. the nurse is going to kill me! (icu syndrome) anita duvndam ~, sonia v.d,sluis ~dpt. of pediatrics, div. pediatric intensive care, sophia children's hospital, rotterdam dpt. of pediatrics, div. pediatric tntensive care, juliana children's hospital, the hague. content description: this presentation will provide the critical nurse with background information concerning the identification, the prevention and management of the critical ill child who has developed the icu syndrome. the results of a questionnaire concerning the occurrence of icu syndrome on a picu will be presented. behavioral objectives: at the end of this session the participant will be able to: . describe four clinical symptoms of the tcu syndrome, . identify major sources of picu environmental stress, . discuss nursing's unique role in helping the child to cope with the icu syndrome, . discuss nursing's unique role in preventing icu syndrome. content outline: the icu syndrome is a situation in which the individual is not able to deal with changes in observation and interpretation of both quantity and of patterns of sensory perceptions. in other words the borders between the inner and outer world becomes unclear for the person. the exact incidence of the icu syndrome in the critical care setting is unknown, we have limited knowledge of the occurrence of the icu syndrome in critical ill children. yet critical ill children in our hospitals sometimes show the symptoms of icu syndromes. to be able to identify the occurrence of icu syndrome we developed a questionnaire. the thesis of the questionnaire was: does the icu syndrome occur in critical ill children in the age between three and ten, who have been intubated and/or ventilated in a picu? eighteen questionnaires have been send out to parents of critical ill children in two hospitals. the response was percent. conclusions: . most of the children were anxious (n= ), showed regression (n= ) or had sleeping problems (n-lo) during the stay on the picu. . children showed the same problems after discharge. . there is no relationship between environmental factors and symptoms of the tcu syndrome during the stay. . there is no relationship between preexistential behavior and symptoms of the icu syndrome during the stay. because the lack of a scientific definition for the icu syndrome in children and good criteria for diagnosis, we were not able to get an answer to our thesis. more research is needed. continuous veno venous haemofiltration (cvvh) was adopted as a first line renal replacement therapy in our paediatric intensive care unit (picu) some three years ago. ~/he process of introduction and development of cvvh proved to be an exciting challenge for nurses as indeed it was for the whole multidisciplinary team involved. we have successfully used cvvh in the treatment of over infants and children, weighing between - kg. the range of conditions treated is ever increasing. to date we have not only used cvvh for patients in renal failure and fluid overload, but also to gain biochemical control in tumour lysis syndrome-and metabolic disorders. other distinct patient benefits in comparison with more conventional means of renal replacement therapies are that, it is a continuous controlled treatment being extremely effective in creating 'space' for nutrition, which is especially important in the fluid restricted, catabolic patient. of paramount importance in providing this level of service is the education and training necessary to impart the skills and knowledge for nurses to become expert practitioners in this field. we now have a teem of highly advanced practitioners who have developed their nursing skills to provide even more holistic care for their patients. this group are embracing new challenges and responding positively to the developing service whilst expanding their knowledge base. this paper will discuss the advantages and disadvantages of cvvh as we have experienced, relating i t to the wide variety of patients we have treated. we wish to share how cvvh has become an accepted role of the picu nurse and how the service has been successfully implemented. integrated care pathways (icp's) define the optimum course of events in the care of a patient with a specific condition, within a set timescale. aims and methods: icp's and case management (cm) were introduced to evaluate and improve clinical practice. icp's were developed for patients undergoing surgery for atrial septal defect (asd) ventricular septal defect (vsd) and fallots tetralogy. they were based on the median experiences of the last patients. patients have been managed using icp's. results: analysis of variation from the icp's shows a reduction in the following potentially avoidable causes of variation: delay in extubation has been reduced from % to %, and patients ( %) were extubated earlier than the median. prolonged stay on the intensive care unit (icu) has decreased from % to %, and patients ( %) were discharged to the ward a day earlier than the median. the number of patients receiving inadequate post operative analgesia has decreased from % to %. delayed feeding after operation has been reduced from % to %. unavoidable delays in extubation and discharge from icu occurred in patients ( %) because of haemodynamic instability" or lung problems. cm utilising individualised pathways for these patients has reduced variation in care which can improve patient outcomes. pathways have been developed for other conditions and it is anticipated that approximately, % of patients will be treated using an icp revision of icp's results in continuous evaluation and improvement of the care provided, conclusions: the use of icp's and cm has improved patient care and decreased avoidable delays and variations. the future development of other icp's, combined with a case managed model for selected patients, is seen as a viable method of continuously improving patient care. this paper is a retrospective audit of children who received continuous veno venous haemofiltration (cwh) whilst on the paediatrie intensive care unit (picu), data was collected over a month period from may to january . the girls and boys were aged from day to ½ years (median ½ years) and weighed between , and kg (median . kg). length of admission to picu was to days (median days). sepsis syndrome was diagnosed in cases: of these had bowel necrosis and meningoceccal disease. eight patients had an underlying haematological, oncolngical or immune disorder. the remaining children had inborn errors of metabolism ( ), nephrotic syndrome ( ), or cardiac failure ( ). cvvh was instituted for a variety of reasons. muttiorgan dysfunction was present in % of patients, % had acute renal failure, . % tumour lysis syndrome, . % uncontrollable metabolic acidosis with hyperammoneemia and % required fluid management. treatment was continued for between hours and days (median ½ days). haemofiltration was successful in achieving its desired effect in all except one patient. . % of children with haematological, ontological or immune disorders died despite successful haemofiltration. survival was higher in cases of septicaemia ( . %), nephrotic syndrome ( %) and errors of metabolism ( %). overall mortality was . %. this was attributed to the severity of the underlying disease process rather than the effectiveness of cvvh as a renal replacement therapy. asynchronous defibrillation and synchronized cardioversion deliver direct currents of high amplitude through the chest, to stop ventricular fibrillation or to convert life-threatening arrhythmias. since the human body is partially conductant, it should be possible that after a brief delay of time, a derivation of this monophasic defibrillation pulse is measurable in regions of the defibrillated body, other than the traject between anodal ("sternum") and cathodai ("ape~;") paddles. one could also estimate that health care personnel in the immediate environment of defibrillatoty shocks, are always at risk to possible electric injury. accidents might occur when health care personnel do not stand clear from the patient during firing and create an additional electric path from this patient through their own body. most likely, the nonisolated parts creating a transversal eiectric path, will be the hands of the caretaker. since defibrillation generates touch voltages up to v and - a in ved, short delay's ( to millisec), the total body resistance during skin to skin or skin to paddle contact, is calculated to be as [ow as ohm (percentile tank for the entire population). an experimental protocol was developed to evaluate the conducted currents during defibrillation. mature pigs with a weight of up to kg. were used as animal models. the:,, had barbiturate anaesthesia, inotropic support with dobutamine at l micmgrams/kg bodyweight and all had a sinasat rhythm at the begining of the test-rounds. synchronized defibrillation at j (approx. . j/kg) and asynchronized -at j (whenever ventricular fibrillation or ventricular tachycardia occurred), were attempted, through latero-lateral placed and firmly pressed defibrillation paddles and/or adhesive multi-function electrodes. gel pads were choosen as contactmedium to cross the skinpaddle barrier. subdermal electro-myography needle electrodes were put at different parts and regions of the pig's body, but not between the paddles. these electrodes were coupled to a resistance device of ohm and a measuring computer. we measured monophasic and low current pulses up to , a during the defibrillation burst. thus conducted currents are high enough to produce accidental electric shocks when additional electric paths are created by the caretaker. "llaese are usually harmless, but in some "worst case" (wet or transpiring hands, rings,...) or in association with defectuous equipment, peak currents might be harmfull, and can produce pain, bums, apnae or cardiac (transient or persistant) arrhythmias. maria skogbv. karin mellgren, lars-g ran friberg, g sta mellgren, hans wadenvik. g teborg, sweden. bleeding complications in extracorporeal circulation is partly due to perfusion-induced platelet dysfunction. the aim of this study was to evaluate an in vitro model for investigation of platelet function parameters in an extracorporeat system. study: two complete extracorporeal life support systems were perfused with fresh heparinized human blood for hours. piatetet membrane glycoprotein changes, platelet granule release and platelet count were followed. eight paired experiments were performed. one of the circuits was perfused by a roller pump (polystan) and the other by a centrifugal pump (biomecicus), other components were identical. results: a continuous increase in glycoprotein (gp) ib-negative platelets was seen in both circuits. a marked increase of plasma beta-thromboglobulin concentration and a decrease of the intracellular pool of serotonin was observed, indicating a marked release of alpha as well as of dense granules. the plasma concentration of glycocalioin increased in parallel with a reduced platelet surface expression of gpib, suggesting that the loss of gpib is caused by proteolysis rather than by a downregulation of this receptor protein. conclusion: hours of ecls perfusion induces pronounced platelet degranutation and causes changes of important membrane receptors. this is in accordance with clinical studies, suggesting that our in vitro model does mirror the platelet exhaustion observed in a clinical reality. no significant difference was observed between the two pumps. the purpose of this study was to examine signs of distress exhibited by several patients following the discontinuation of opioids and benzodiazepines (o & b) in a -bed pediatric intensive care unit. the authors compiled a list of all cases of possible withdrawal reactions reported by nurses in the study setting over a one-year period. five cases were selected for study in terms of their wide diversity of relevant circumstances. the cases were examined through a retrospective chart review. data pertaining to analgesic and sedative administration, along with nurses' reports of behavioral distress, were transcribed and coded. a remarkable pattern of behavioral distress was clearly associated with discontinuation of o & b. cessation of benzodiazepines was associated with severe distress. these reactions were characterized by various combinations of crying, irritability, tremors, grimacing, gagging, vomiting, or feeding problems. some of these persisted in spite of large amounts of bolus drug administration. these signs were manifested for to days following cessation of o & b. these findings demonstrate that the rapid weaning of o & b infusions, sometimes following short-term therapy, can cause severe withdrawal reactions. the particular course that a specific patient will follow will likely be modulated by underlying manifestations of "icu psychosis" and unresolved pain and emotional distress. hermana tezano mt, pilaf orive j, latorre garcia j, lizarraga azparren ma, lopez bayon j ucip hospital de cruces. bilbao. spain a female child, one year old, was referred to our unit from another hospital because she had ischemic syntomsjn her right forearm wich started three days before. she had ~i downs syndrome and fallot's tetralogy with a systemic-pulmonary by-pass. nine days before the admission in our hospital she was undergone to a cardiac catheterization by arterial and venous femoral punctures with no incidences. on the admission to the picu her forearm was cold and pale with absence of cubital and radial pulses and slow capilary filling. treatment with heparine was started unsucessfully in the firsts hours, so uroquinase was added that later was changed to rtpa plus brachial plexus blockade. by the time me arterial tlux became more and more evident (doppi~) il bccuute aiat) evident a regional aedema witch made necessary a fasciectomy &the wrist. she also developped necrotic delimitted areas that included her first and fifth fingers. she was discharged from the picu after days and a week later she went to the operating room where an amputation of the distal phalange of the fifth finger was made. the etiolgy of this ischemic picture can't be attributed to the catheterization itself, but probably it should be due to some attempts in arterial puncture in its course, attempts that could be guess by the little marks noticed at the elbow flexure when she was admitted. long maintenance of cardiovascular funtion by assisted ventricular device with membrane oxigenator hermana tezanos mt, pilar orive j. latorre garcia j, lizarraga azparren ma lopez bay n j. ucip. hospital de cruces. bilbao. spain a little girl of three and a half years came to the intensive care unit from the operating room. affected of great vessels transposition with a pulmona~' banding corrected vith rastelli technique, it became impossible to discharge her from the by-pass circulation. it was assumed that this factt was due to a transient myocardial disfunction dfter the surgeon x~ent through the technique and found no wrong step in it. at the picu admission she had an ejection fraction belox~ % (echncardiografy), and was manteined on veutricular assistance with a circuit consisting ofa plate's membrane oxigenator, a bio-medicus pump and pvc rubber tubes, with monitoring of pulmonary', right and left atrial pressures. initially she needed a ventncular support of . l/min with dopamine. dobutamine and adrenaline; gradually the ejection fraction rose to % aliowing a decrease in the mechanical and inotropic support. the organic function ,.'.-as preserved but x-ray of the thorax showed images of pulmonary aedema with an increase in the needs until a fi of . . even though she was placed in a transplant program, she was remouved when the ejection fraction rose to % on the lth da of the evolution. there were no signs of infection (profilactic coverage). on the fifhteen postsurgery day. with a good cardiac sound and an ejection fraction of at least %. it was considered the withdrawal of the ventficular support, but unsucessfully despite the increase ofinotropic drugs, so she died. we think that our patient is a good example of the posibiti~ to mantain x~ith ecmo during a prolonged period of time a potential transplant receiver without major complicatios. joan wierema; ma )an mourik. sophia children's hospital, department of pediatric surger,j, rotterdam, the netherlands. the success of an ecmo program is heavily determined by the organizational structure and the daily availability of both well trained nurses and physicians. until now there is no general guideline to determine the optimal training schedule to set up an ecmo program. objective: to evaluate the set-up of an ecmo program in an area without direct availability of perfusionists of cardiothoracic surgeons. description of the progress: during the preparation of the ecmo program which started november , different phases are identified. first phase, acquisition of experience by training abroad of one physician, staff member of the icu, physician acting as a fellow and one icu nurse with theprimary task to serve as an ecmo coordinator and train the nursing start. in the second phase animal experiments were performed by paediatric surgeons, staff physicians, fellows and nurses. third phase, start of the actual ecmo program, priming by one trained nurse and ecmo fellow, daily care of the patient by nurses, icu nurse taking care of the patient related activities, ecmo trained nurse taking care of the circuit. fourth phase, transition of the tasks for priming the system from the ecmo fellow to the ecmo nurse and changing daily care for the ecmo patient now including the circuit by trained icu nurse with special legislation for ecmo. ongoing training of to nurses working for at least half a year in the icu. during an ecmo run direct contact between the ecmo nurse and one of the staff members; patient data: in a year period neonatal ecmo cases were performed with an overall mortality of %, ranging from over % in meconium aspiration to % in congenital diaphragmatic hernia. in other patients pediatric ecmo (age range month - months) mortality was %. conclusions: ecmo can be established without perfusionists or cardio surgical back up once a predetermined training schedule is available, resulting in comparable results with the international ecmo registry both for neonatal as well as for pediatric cases. mechanical ventilation at home makes normal development of the child with chronic respiratory failure possible. the parents must be encouraged to accept the treatment at home; therefore, they should be enabled to take care of their children all by themselves and the continuous professional support has to be offered to them. it must be stressed that the nurse is the link between the diseased child and his family introducing them into the process of the medical care at home. all the equipment needed for the mechanical ventilation of the child at home (ventilator, suction device, pulse oxymeter, oxygen tanks) has to be provided before the child is discharged. it is paid by the national insurance company. the maintainance service workers will make the necessary installations available and they will renew oxygen and compressed air weekly. the ventilation assembly must not interfere with the childs activities. the related dispensary and nursing service should be notified of the child's condition and the list of the required material (suction tubes, cannulas, desinfectants etc.) has to be made. our experience is so far -from the nursing and medical point of view -satisfactory, however the social status of the parents needs further regulations, omphalocele. mourik m, sophia children's hospital, department of pediatric surgery, rotterdam, the netherlands. in patients with (giant) omphalocde operative closure is impossible due to the lack of intra-abdominal space and a variable degree of pulmonary hypoplasia. consequently conservative treatment allowing epithelialization is the treatment of choice with a high risk of infection and/or sepsis due to a sometimes very long stay in the icu. this conservative treatment consists of daily application of an antibiotic containing powder on the cele which is covered by sterile gauzes. furthermore the enteral intake is started as soon possible. objective: to evaluate whether this treatment renders a high risk for serious infections. patient characteristics: in a year period patients with a giant omphalocele were admitted; mean birth weight g ( - g) mean gestational age . ( - weeks). overall mortality ( %). patients had to be ventilated for a median duration of t days ( , - ). results: patients were discharged at the mean of days following birth ( - ) following complete epithelialization of the omphalocele. following the initial stabilisation period parents were involved in daily care of all patients even during artificial ventialation. enteral intake was started at a median of days ( - ). colonization of the omphalocele was observed within - days in all patients. although infectious periods were observed at regular intervals, sepsis was the primarily cause of death in only of the patients who died, in conclusion: nursing care to prevent sepsis in patients with (giant) omphalocele is feasible for a long period of time and can be performed with simple measures, since june , we have been using nasal cpap in the treatment of respiratory disorders in newborn infants (severe apnea syndrom, tachypnea, hyaline membrane disease). in newborns presenting hyaline membrane disease, we have used cpap and administered surfactant therapy to premature babies out of . clinical data were : mean ga : . + weeks. mean bw : + g. mean administration time was hours. before administration, mean fio was . + . , mean pao . + . kpa and mean a/ao ratio . . all babies were intubated for administration of surfactant (curosurf) and were extubated after half an hour to hours after administration. this treatment failed for seven babies and they were ventilated by oscillation ventilation ; all babies survived. complications : we have observed pneumothorax in cases and cerebral hemorrage. mean duration time of nasal cpap was hours for the babies without assisted ventilation. nurses in charge of babies with nasal cpap should be aware of neonatal care, of the possibility of surfactant administration and of complications during this type of treatment. therefore nurses should know very well the use of nasal cpap, the monitoring during this treatment, the fixation of the system on the baby, nursing of the babies during this treatment and finally should take care of the baby physical and psychological well being. as a conclusion, nurses in intensive care neonatal units should know the possibility of treatment of rds by nasal cpap and should be aware of baby-nursing. emco in the postcardiotomy infan_t : a simplified circuit and reduced management grillet lsabelle, bosson christa, goelz andrea, helmer pascale, icu nurses, tschaut rudy perfusianist aldo castaneda institute, clinique de genolier, suisse to improve postoperative survival of infants with repaired cardiac tessions but severe residual cardiopnlmonary dysfunction, emco was used in infants, ranging in age from l days to months and in weight from , kg to , kg. diagnosis included tga / intact ventricular septum ( ) (both subiected to rapid arterial switch operation because of unsuitable lv function) and tga +vsd ( ). "['he emco circuit included a sarns roller ump, a medtronic minimax plus hollow fiber oxygenator and tubing ( / - / inch) with bioactive surfaces, an arterial canula fr., venous canulas : right atrial fr, left atrial fr., an air oxygen mixer and a sarns heater. the act was kept between - sec. after the infant was connected to emco by the surgical team and the perfusion technologist, the patients were being cared for and controlled exclusively by the cu nurse assigned to the patient and the physician on call for the icu, pump flows of - ml / kg / mln were targeted to insure an adequate urine output, a brisk capillary fill and physiologic left and right atrial pressures. sodium nitroprusside was used to control systemic hypertension while all other inotropic drugs were discontinued. inspired oxygen fraction on the ventilator was reduced to , at a respiratory rate of - breaths per minute. body temperature was maintened close to normal. when the heart started to eject again, inspired oxygen was increased to about , . the preparation for weaning from emco was done by the icu nurse: including oxygen fraction and ventilator rate. weaning from emcowas coordinated by the medical / surgical team and the perfusion technologist. the duration of emco in the patients ranged from to days. three patients ( %) were saccessflly weaned from emco. one of the three died within hours from neurologic complications, unrelated to the emco. the other patients ( both with tga + vsd ) are long term survivors and are doing well. neither the survivors nor the patients who died bad hemorrhagic complications, despite the fact that of the were placed on emco because of failure to wean from cardiopulmonary bypass. the simplified emco circuit worked reliably throughout this experience and no complications occurred nor could any shortcoming be ascribed to the use of this reduced, cost effective management team. years of praciical experience wiih exiracorporeal membrane oxygenation (echo) -the viewpoint of the nursing siaef monika schindler in a training program was started for the introduction of echo in the kinderklinik of mannheim/germsny. years later ( ) the first european echo patient, a days old newborn baby, ~as treated successfully in our institution. with echo, more treatment modalities ~ere available after failure of conventional therapy in eases of severe lung diseases like meeonium aspiration syndrome, congenital diaphragmatic hernia, sepsis/pneumonia, primary persistent pulmonary hypertension of the newborn and -in infants and children -ards (acquired respiratory distress syndrome) due to multiple underlying illnesses. in the first ards patient, a years old girl, was treated successfully ~ith ecmo in mannheim. until now patients (age: i day - years) were treated with echo in our institution; additional patients were transferred to us from other institutions for therapy with echo, but could be treated ~ieh alternative moda]ities of therapy like improved conventional ventilatory support, high frequency oscillatory ventilation (hfov) and inhaled nieric oxide (no), unexpectedly the more ~ide-spread use of hfov and no -also in other ~ntensive care units -did not lead to a reduction of the echo frequency in our hospital. due to this long ecmo practice, which is helpful in many critical situations, a certain routine came up in the nursing staff of our intensive care units; but ecmo continues to be a maximum strain for all co-workers and implies an high personnel and material/financial-expense. but in our opinion the improved survival rates in severe respiratory failure-( % in neonates and % in infants and children, estimated survival rates under continued conventional management: < %) by the use of echo justifies this expense, even in times of less financial support for public health. • analyse the differences between each urdt. method : ni criteria were defined by the rt~a ped group according to cdc criteria. all data were collected by a nursing and medical team. data vere dealed with epi info software. all u-dections data were validated by an external mvestigatol : patients who stay more than hours in an icu were included over a months period. % were newborns, % infants and , % children. ni were idenlified among sll patients, the overall ni incidence rates was , % and , person day, septicemia was the first cause of ni ( %). staphylococcus epidermidis were isolated in % of septicemia cases. pneumonia was the other main ni ( %) with gram negatwe bacille isolated m % ( % of them beei,ng fseudomonas) accordmg to age, the septicemia mcidence rate varied from , ~., to . %,, catheter/day and pneumonia incidence rate from , %, to , % ventilation/daywith the lowest rate for newborns. : this survey was possible thanks to the collaboration between laboratories, bacteriologist, physicians and nurses, and allowed each concerned unit to work together in~tead of every one in his own field. 'lhe results of this survey bring changes in attlhades and empower the different team work the next step is to analyse the ditferent nurses procedures of indwelling central venous catheter in each unit ar)d implement a ni quatity care. program in all nicu anti picu. v~,~jl~j~'v~y : new born in~ra-v~ nous drugs ~md lheir pr~taration mcounter a lot of risk ~)f utters, due to inadapted conditionn~ng to podia)eric and minimal amount injec~.~d, th~ study t~ed to evaluate degrees of do.~age er~o~ dye tt) dru~ preparaek, n i~ nc,:,~atol~gy and to come out w~th ~ method of dihttion able to reduce risk to minima (errors _< %) at the ~eme t~me, ¢o~,~x-tueaces on cost were studioj methnd~ : amikacine was choosen because this antibiotic is regularly ~,~l in neonatology unit and its dosage is easily used by standardiaud method, amikacine doses ( , mg doses and , mg doses) were prepared" by nurse~ form mg for m) vial. each dose w'a~ diluted to obtain mi volume, tallowing usual ward method, for each dilution, amikacine con<entrati('m and it,s volume was measured and used equipment for preparation wa~ regi~tred. "first s utj(m" were prepared diluting ~t'~ mg amikacine pouder inn ) ml glucnse solution bag (viaflex baxter bag with transfer cap), from tho~e "first solution" doses at mg and doses of ~ rng were prepared, amik~cine coc, cenir,)tmn for each preparabon and their volume were measured, ai,~n ntttl~,ber of seringe were tounted. first soiuhon staeiiity was conrroieo aher one week conservation at + '>c. amjkacine concentration were measured by fluorescence process (tdx abbott) after sample dilurion. on a mg/l sample, tovhnical reliahility show~ > ~ % of result mpmductlon and < % of variation due to dilutions. results : when amikacine injection werv pro.pared from araikacme /) mg for mt vial > % do~ge, ermr~ were found in / cases ; ~ % in ,t ,to cases. if preparation is done from amikacine "~it'st soltltion", les.--concenvr~tcd, it i~ more preci,,,e and only one dosage error ~ % ( , %} is found in eli studied doses. in add)inn to )hal if doses were wep,m-'d from one "first soiatiol~' bag, the cost economy sl~ouid b~" of fr~, and ii dos~$ were prepared tram the same bag the saving mtmey should be o{ i its .cencluslon : .ur survey shows th~t h' ntu)nato|ogy the u~ of a "first sohation which can be kept fi~r one week is enable to reduce dosage erroes and i~ co,~tsavmg, regarding [,v. admimst'rahon method the survey is still on, introduction: so-called vein of galen m~iformations ale rare in~racranial embryologycal anomalies, repl~senti~g tess than of symptomatic intracranied artefiovenoas l~alform~tions. the spontlneous prognosis is ~s~u~lly fatal, because of cardiac frilure due to left-to-right shunt thrq~ugh the fistula. recent developments of new techniques of treatment of the malformation and its cardiac consequence have led to a revolution in the practical approach of children w~th galen malformation. our fukfose is to contribute, with our persoaal series of s newborns and infal~ts admitted in our unit after endov~,scular embolization, to a better management of these children. such a management requ!res a rnultidisciplinary approach. intensive care are required prior to embollzation for patients with cardiac failure or cardiogenic shock and after cmbolization in order to insure cardiac and cerebral hemodyna.mic stabilities. this overlooking suppose for the nursing team to understand: prior to embolization : heart failure and cardiogenic shock. after cmbolization : evaluation of neurological and hemodynamic consequences of this proccdure, without forgetting the nursing and psychologic aspects, in concl'iision, this last ten yerrs, these new approaches give to the patients and their famitiy a good reason to hope a total recovew, in our exl)erience, the global mortality is % aad % of children #j-e neurologically normal after embolizafion, ii ii~ i ~ii i ii i i l i iiii~ i ~i iii i background: venous oxygen saturation (svo z) reflects the residuai oxygen after tissue oxygen extraction and represents the relation between tissue oxygen supply and demand. we studied svo and arterial lactate during progressive isovolemic anemia to assess the relation between svo and tissue hypoxia. subjects: ten - day old anesthetized ventilated piglets sao and svq were measured continuously by a fiberoptic catheter (oximetrix, abbott lab.) in the carotid and pulmonary a~epy tissue hypoxia was confirmed by a reduced vo, and an increase in lactate. conclusion: svo reflects better a reduced dp obtained by progressive anemia surfactant replacement improves gas exchange in early-stage adult respiratory syndrome (ards) [ , ], but not in late-stage ards [ ] . we report the first case of successfull treatment of ards after repeated instillation of surfactant.a ten year old boy, weighing kg, presented with hemorragic shock. biphasic-positive-airways-pressure ventilation was performed (evita ii, dr~ger, germany). he had recieved nine units of packed red blood cells and underwent surgical exeresis of two bleeding gastric ulcus. post-operatively, a cardiac arrest required cardiopulmonary resuscitation for three minutes. hemodynamic status was subsequently stabilised. the chest-radiograph showed infiltrates of both lungs without signs of cardiac failure. on the third day, the patient became severely hypoxic with a pao /fio ratio of . gas exchange was not improved by high ventilator settings. peak inspiratory pressure (pip) and ventilatory rates were cmh~o and breaths/min respectively. inspiratory:expiratory time was : and the positive end expiratory pressure (peep) cmh . after increasing the peep level to cmh , we instilled over minutes, mg/kg of porcine surfactant (curosurf, serene france), in two equal volumes in both main bronchus,the spo~ rose to % within rain, the fie could be reduced to . . twenty four hours later, gas exchange worsened again (pao /fio ratio ). we increased the peep from to cmh , and instilled a second dose of surfactant ( mg/kg). again, fie could be reduced within minutes (spo ; fie . .). the patient was weaned from the ventilator and extubated on the tenth day. follow-up at four month showed normal lung function.we demonstrate improvement in oxygenation after repeated exogenous surfactant administrations. we assume that in early-stage ards, surfactant may potentiate shunt-reducing effect of peep as it has been demonstrated in experimental model of ards [ ] , and allow decrease in fie . in case of secondary deterioration, we think that a second dose of surfactant should be administered. . weg jg, balk ra, tharratt rs, et al. ,lama : : - . . spragg rg, gillard n, pdchman p, et al. chest t : : - . . haslam pl, hughes da, mcnaughton pd. et al. lancet : - . . huang yc, caimulti sp, fawcett ta, et al. jappl physiol : - % (ref) . the aim of this study was to verify these data: patients/~lethods: all pts admitted to our multidisciplinary nicu/picu in were included if they were in respiratory failure recruiting conventional mechanical ventilation (cmv) with peep >_ and 'fig -: % or high-frequency oscillation ventilation (hfo) with mean airway pressure _> t cm h for or more houm. diagnosis, maximal ventilatory parameters, barotrauma, organ/ system failures, mechanism of death and glasgow oulcome scale (gos) and months after study entry were prospectively collected. results: patients were admitted to the unit, o whom required mechanical ventilation for a mean duration of . days. overall mortality was %, patients fulfilled study criteria. survivors had gos , pts with preexisting neurological impairment survived with gos . neonatal diseases included hyaline membrane disease ( ), meconium aspiration syndrome ( ) and cardiovascular surgery ( ), pediatric diseases included bacterial ( ) and viral ( ) pneumonia, aspiration ( ) and cardiovascular surgery beyond the neonatal period ( ). - ) . patients and methods: cefotaxim was used as a prophylactic agent in patients in life threatening situations (e.g. multitrauma, neurosurgery atc.). more than % children required cefotaxim for the treatment of severe infections (epiglotitis, meningitis, sepsis, pneumonia mainly in immunodeficient and neutropenic patients) in monotherapy or in the combination with the other antimicrobial agents. results: cefotaxim as a prophylactic drug was successful in all cases ( %). the effectivity of treatment of infections was . % ( patients). the change of antibiotic therapy required patients ( . %). patients ( . %) died, but only in of them ( . %) the obduction confirmed infection. conclusion: we conclude that cefotaxim is very effective and safe antibiotic and represents "golden standard" in the treatment of severe infections in childhood. in order to improve nursing quality, we recently adapted nursing care to the "five nursing functions" (activities of daily living, accompagnment in crisis, treatment, prevention and research) as described by the swiss red cross in accordance to the new educational guidelines of the european community, the aim of this study was to document complications of "treatment nursing function".methods: all treatment complications were prospectively collected by the nursing and medical staff. the nursing staff included patient (pt) name, time of occurence and exact description of complication, proposal for prevention and information of parents. the medical staff reported type of complication together with pt information, diagnosis, medication, treatment and interventions, outcome and referral, all complications were discussed in monthly meetings including nursing and medical staff.results: from january until december , pts were admitted to the picu/nicu for nursing days ( % of total bed occupancy). pts needed endotracheal intubation for an average of . days and pts required nasal cpap. complications in pts were noted ( per pi): inadequate check-up of equipment ; accidental extubation ( in intubated pts); bedsores ; false drug dosing ; wrong drug ; umbilical bleeding ; wrong transfusion setup ; nasal septal necrosis ). there was no mortality due to these complications. exact documention of treatment complications and their meticulous discussion within the medical and nursing staff may improve "treatment nursing function". however, documentation and evaluation of nursing within all "five nursing functions" will be nessecary in order to achieve optimal nursing care. cardiac output determination by thermodilution, using iced injectate has been shown to be valid and reliable in pediatric patients. it has been demonstrated in adult patients that there is no difference in cardiac output values when using room temperature injectate as compared to iced temperature injectate. the purpose of this study is to examine the effect of injectate temperature on cardiac output values in pediatric patients. our study consisted of sixteen pediatric patients who had oximetric thermodilution catheters in place after cardiac surgery and who had cardiac output determined using both iced and room temperature injectate. with each patient, cardiac output was measured once on the day of surgery and again the following day. in each case cardiac output was measured using both iced and room temperature injectate. statistical analysis included a two-way, repeated measures analysis of variance for each individual injectate administered and no significant differences were found in cardiac output. no statistically significant differences were found between groups with regard to the order of injectate administration or volume of injectate used (i,e., or cc's). the correlation coefficients between groups for cardiac output measurements at each injectate administration time, and for the average measurements across times, ranged between . to . (p < . ). preliminary data analysis suggests that cardiac output measurements for children are not effected by the temperature of injectate. a lenghty stay at a paediatric intensive care unit will always have sideeffects on a child's well-being and will put a high strain on the parents. in order to minimize the side-effects longterm intensive care unit opened in at the childrens' hospital. admitted children are all ~ongterm-ill and technically-dependent and the ventilatory support can alter from a tracheostoma to cpap or portable volume ventilator. nutritional support is applied by gastrostomies. a homelike atmosphere surrounds the children, they share a dormitory, a living-room and a dining-room the main purpose is to send the child home with or without technical equipment. this can only be implemented by giving structured education (theory and practice) to all categories involved. the multi-disciplinary team consists of one anaesthesiologist, head nurse, clinical specialist, rn nurses, nurses, one habilitation doctor, one social worker and therapists. twenty-four patients have been admitted to licu during these six years. length of stay was from one day to four years. four are presently staying at the trait. the assessment of pain in children ( - yrs) is still difficult, because children of this age have limited language and cognitive skills. to standardize the assessment of postoperative pain and distress in the intensive care unit an observational mstrument was needed that met several criteria. it should be easy to use in daily routine care. be suitable for the i.c. situation, and in children of - hrs of age. the comfort scale, an observational instrument designed to assess distress in infants in i.c. units, met these criteria. to accommodate the use of the comfort scale in the i.c. units and in research, nurses should be trained to use the scale. an additional requirement was that the inter-rater reliability should be sufficiently high, (cohen's kappa > . ). objectives: ) to introduce the comfort scale in the i.c.u.; ) to examine whether this instrument can easily, be incorporated into routine care; ) to investigate the inter-rater retiabtlity. methods: the comfort scale is an -item instrument specifically designed for use in pediatric i,c, units and contains both physiological items (heart rate, blood pressure) and behavioral items (e.g., alertness behavior, calmness/agitation, body movement, facial expression respiratory response, muscle tension). the observation period is minutes. the scale is supplemented with an item on crying tbr children who are not mechanically ventilated. groups of t.c. nurses were trained by means of video's and observations at the wards. after the training, each nurse completed scores with other nurses, after which the cohen's kappa was computed. when the kappa's for the items met or exceeded our . criterium, a new group of nurses was trained. results: to date, nurses have been trained. nurses find the comfort scale easy" to administer and a valuable addition to routine care in the i.c. unit. the cohen's kappa's were higher than . for all items that the inter-rater reliability was high. the comfort scale is feasible in postoperative care in the i.v. and is considered a valuable instrument to improve and maintain high postoperative quality of care in the i.c. unit. introduction:children with neuro-muscular disease are believed to have a higher resting energy expenditure (ree), because of their increasedwork of breathing.the influence of nocturnal nasal mask ventilation on energy metabolism and nutritional state of these children has not been studied so far.objective:l,ls the ree inereased? . s there an influence of nasal mask ventilation on the ree? .what is the nutritional state? .what is the estimated total energy expenditure(ete) in relation to the caloric intake? methods:a pilot study of patients( - years) .the following measurements were performed:l.anthropometry. .bioelectric impedance- .ree was measured by indirect calorimetry during the day (in bed) with and without nasal mask ventuation,ree was compared with predicted ree according to schofield(pee), .caloric-intake and activities were recorded during hour before measurement. .total energy expenditure was calculated as follows:measured ree x estimated activity factor. results:tin all children weight for height was too low, <p . .aii children had a low % of fat. .according to the healthy group, ree is not increased. ,nasal mask ventilation lowered ree in patients, in patient we measured a clear decrease.conclueion:l.anthropometry and indirect calorimetry were helpful in evaluating the nutritional state. .there is no increased ree,in t patient there is clearly effect of nasal mask ventilation. .when caloric intake was related to ree and level of activity patients had too low caloric intake. .the influence of nocturnal nasal mask ventilation and nutritional assessment should be evaluated longitudinally. increasing awareness that the neonate can percept pain and suffer following surgical procedures, has major impact on pain management. in our unit continuous morphine infusion (t /~g/kg/hr) was introduced from january as a standard medicatton following surgical procedures. before morphine was given as a bolus (i.m., i.v., rectal) of /~g/kg up till four times a day. repeated gifts of morphine were only gwen following observation by the nurse that the child experienced pain. aim of the study: to evaluate pain management before and tbllowing introduction of a continuous morphine infusion for postoperative pain in our icu. patients and methods: term born babies with isolated oesophageal atresia and tracheo-oesophageal fistula were included in the study. the total amount of morphine (/~£/kg/ hours); number of days morphine was given; duration of artificial ventilation was evaluated in a case control study. res ults: - - central venous catheters (cvc) have been increasingly used also at our picu, university medical centre ljubljana. besides advantages, the cvc has brought numerous risks of complications; the catheter sepsis occurs most often and can be fatal for the patient. for example, in we dealt with children aged - years or in other words . cvp per a child treated at our picu. a specialized unit for preparing parenteral natrition started to function in the university medical centre pharmacy in . after that we equipped a special room for preparing other necessary infusion mixtures and organized a team of nurses -"catheter nurses".their tasks comprise: managing cvcs, replacing and installing infusion systems and mixtures made at pharmacy, preparing drugs and some necessary infusion mixtures in special room, permanent training and co-operation with related disciplines, pharmacy, epidemiology, microbiology, etc. all registered nurses at picu have been trained for this work. the routine is as follows: in the morningafter the doctor's visit, we first check the cvc and change the dressings; according to the nurse's observations, the doctor decides whether there is a need to remove or replace the cvc. if the catheter site is inflamed, swollen, or purulent, a swab is taken for microbiological culture and the area cleaned. in case of systemic infection signs, cvc has to be replaced, blood culture taken and the infection treated with antibiotics. the dressings are always changed by two tmcatheter nurses together. afterwards the infusion mixtures for the next hours are prepared for each child. the infusion mixtures which will not be used immediately are kept on + °c; before application they are, of course, warmed to at least room temperature. finally the "catheter nurse" supplies the cvc with new infusion mixtures made at our pharmacy. our observations show that such work requires responsibility and is demanding; but our pemanent care lessens the number of complications. thus the described scheme fulfilled our expectations. perl- perative management of neonates with hypoplastic left heart syndrome muir warren, blondel maryse, foltz rhonda, farine martine, icu nurses, the aldo castaneda institute, clinique de genolier, switzerland both the pre-operative and post-operative physiology of patient with hypoplastic left heart syndrome is critically determined by the puhnonary-tosystemic resistance ratio. a high ratio results in minimum volume work for the right ventricle but is at the expense of important hypoxemia. a low ratio is reflected in minimum hypoxemia but an unfavorable increase in excess ventricular volume work. a resistance ratio of approximately results in an arterial oxygen saturation of % - %, a qp/qs of , and ventricular volume work only twice normal. this latter physiology appears best for oxygen delivery and systemic perfusion with tolerable volume work. carbon dioxide (co ) in the inspired gas is known to increase pulmonary vascular resistance without significantly influencing systemic resistance in the range of to tort partial pressure. hyperventilation with no co in inspired gas decreases pulmonary vascular resistance. thus, managing co may be useful to modulate the pulmonary-to-systemic resistance ratio, in the tast months, patients with hypoplastic left heart syndrome were managed by a norwood procedur e. patients with endotracheal entubation pre-operatively had co added to inspired gas to modulate the pulmonary-to-systemic flow ratio. patients had co added to inspired gas post-operatively. all but patient had characteristically large pulmonaary-to-systemic flow ratio with oxygen saturation mean % preoperatively, even in those patients receiving co , co was accompanied by elimination of metabolic acidosis pre-operatively. the most comlnon partial pressure of co added post-operatively was torr. po ranged from mmhg to mmhg. all surviving patients developed a metabolic alkalosis ( mean) when treated with co . there were deaths, one from drug toxicity, one from excessive post-operative hemorrhage, two from sepsis or mocardial insufficiency. only one patient benefited from catecholamine support which can increase systemic resistance unfaborably. in this experience co was felt to be an important adjunct in some patients pre-operatively and most patients postoperatively to faborably modulate the critically important systemic-topulmonary flow ratio, to maximize oxygen delivery and systemic perfusion, while minimizing excessive right vantricular volume work. key: cord- - uckmya authors: nan title: akzeptierte abstracts für die covid- -bedingt abgesagte dgiin/Ögiain-jahrestagung date: - - journal: med klin intensivmed notfmed doi: . /s - - - sha: doc_id: cord_uid: uckmya nan sehr geehrte leserinnen und leser, dieses jahr hätte die gemeinsame jahrestagung der dgiin und Ögiain als . jahrestagung in salzburg stattfinden sollte. leider kam die covid- -krise dazwischen, und trotz der weit fortgeschrittenen planungen war es unter einhaltung der gesetzlichen vorgaben nicht mehr möglich, eine so große tagung durchzuführen. die planungen beinhalteten auch bereits die evaluierung der eingereichten abstracts. da wir trotz der absage der tagung die autoren, die sich der mühe unterzogen, ihre arbeiten in einem abstract zusammenzufassen, nicht leer ausgehen lassen wollten, haben wir uns entschieden, die von den gutachtern akzeptierten abstracts in dieser ausgabe der zeitschrift medizinische klinik -intensivmedizin und notfallmedizin zu publizieren. somit soll den autoren gelegenheit gegeben werden, ihre daten trotzdem einem breiteren publikum präsentieren zu können. nach den derzeitigen planungen wird die jahrestagung im jahr wieder in salzburg stattfinden. wir hoffen, dass uns die mitglieder der dgiin und Ögiain dann auch wieder die treue halten, und wünschen ihnen eine interessante lektüre mit den abstracts der heuer leider ausgefallenen jahrestagung. results: in septic patients we observed a statistically significant decrease in the density of capillaries with a diameter of µm (d : . vs. . mm - , p = . ), µm (d : . vs. . mm - , p = . ) and µm (d : . vs. . mm - , p = . ) compared to healthy controls. furthermore, d , d and d correlated well with several markers of inflammation and critical illness such as lactate (d : rs = - . , p = . ; d : rs = - . , p = . ; d : rs = - . , p = . ), sequential organ failure assessment (sofa) score (d : rs = - . , p = . ; d : rs = - . , p = . ; d : rs = - . , p = . ), interleukin- (d : rs = - . , p = . ; d : rs = - . , p = . ) and procalcitonin (d : rs = - . , p = . ; d : rs = - . , p = . ). of note, capillary density in the larger diameter classes of - µm were neither different between patients and controls, nor did they show a meaningful correlation with relevant clinical parameters. conclusion: our data support the hypothesis that microcirculatory impairment in sepsis does not affect all microvessels under µm, but especially the "real capillaries" with a diameter between - µm. therefore, a detailed diameter-based assessment of the microvasculature should be evaluated in the future. aim: improvements in cannula removal techniques and in particular, a standardized decannulation technique with a suitable closure device, are needed to further improve patient outcomes after percutaneous cannulation. the decannulation techniques described so far are neither sufficiently standardized nor proven enough to be used in the large group of venoarterial extracorporeal membrane oxygenation patients. to meet this challenge, we have established a highly standardized and safe decannulation technique based on the perclose proglide closure system (abbott vascular). methods: establishment of a highly standardized and safe decannulation technique based on the perclose proglide closure system, which is described in detail with comprehensive instructions for the executive clinician and first application in the context of a pilot study. results: so far our technique has already been used successfully in patients since january as a standard procedure on our intensive care unít (icu) with only one minor complication after the first procedure, i. e. a small pseudoaneurysm likely originating from antegrade perfusion puncture site which was sealed by thrombin injection. conclusions: our crossed proglide technique using a hemostasis valve y connector ensuring no blood loss seems to be a very promising decannulation technique. purpose: dysfunctional alterations of the microcirculation play a key role in the development of organ damage in sepsis. therefore, early detection and monitoring of microvascular alterations has been recognized as an important goal in critical care medicine. in this study, we highlight the importance of a quantitative diameter-based analysis approach. methods: this prospective, observational, cross-sectional study included critically ill septic patients (sepsis ) recruited from the intensive care units of a university hospital and healthy volunteers served as controls. we used a sidestream dark field (sdf) camera paired with a data acquisition and analysis software (glycocheck™) to assess the sublingual microvessels. about videos ( vascular segments) per participant were acquired. using an automated data analysis, the density of red blood cells contained in microvessels (diameter - µm) was quantified and subdivided according to their particular diameter classes ( µm each). dererlangung des kreislaufes (rosc) war median ( - ) min. ein erneuter herz-kreislauf-stillstand im rahmen des icu-aufenthaltes wurde bei % (n = ) der patienten beobachtet. insgesamt überlebten % (n = ) der patienten nach hks den icu-aufenthalt, davon ein großteil ( %, n = ) mit gutem neurologischem outcome (cpc i/ii) nach reanimation. schlussfolgerung ("conclusion"): das auftreten eines hks auf der icu ist mit einer hohen mortalität vergesellschaftet. der hks ereignet sich in etwa der hälfte der fälle innerhalb der ersten h nach icu-aufnahme und ist selten kardialer genese. high to low bicarbonate replacement fluid switch in alkalotic patients during continuous venovenous hemofiltration with regional citrate anticoagulation-a retrospective single centre analysis goal of the study: the aim of our study was to compare the replacement fluids (rf) phoxilium ( mmol/ l hco -) and biphozyl ( mmol/ l hco -) during continuous renal replacement therapy (cvvh) with regional citrate anticoagulation (rca) in alkalotic critically ill patients. consequently, we hypothesized that the hco -, hypothesis (h ), be (h ) and co (h ) levels would significantly decrease after the rf change (phoxilium to biphozyl), with the ph (h ) stabilizing thereafter at physiological levels. methods: this retrospective study evaluated intensive care unit patients who underwent cvvh with rca between and . patients were eligible for inclusion if they were ) aged ≥ years, ) admitted to icu, had ) the indications for cvvh as determined by the attending physician, ) a change of replacement fluid from phoxilium® to biphozyl® based on a persistent blood hco -concentration ≥ mmol/ l. patients were excluded in case of cvvh duration less than h and < h of cvvh treatment duration with phoxilium® as well as biphozyl®. overall targeted observation period including data collection was from - h until + h around rf switch. student's t-test was used to test h - . all tests were -sided (significance level %). results: in the study ( male, female, mean age years, bmi ) out of cvvh-rca patients were eligible for analysis. after switching the rf the mean hco -[h ] significantly decreased from . mmol/l (sd± . mmol/l) to . mmol/l (sd± . mmol/l) within h (p = . ). the mean be [h ] significantly decreased from . mmol/l (sd± . mmol/l) to . mmol/l (sd± . mmol/l) within h (p = . ). the mean paco [h ] decrease from . mmhg (sd± . mmhg) to . mmhg (sd± . mmhg) within h was not significant (p = . ). during the rf change the mean ph [h ] was . (sd± . ) and did not change significantly for at least h (ph . , sd± . ) thereafter (p = . ) (. fig. ) . conclusions: switching from high to low bicarbonate rf in alkalotic patients during cvvh with rca seems to be an appropriate approach for acid-base control, although the paco was not significantly decreased. further research is warranted. gender differences in acid-base metabolism during continuous venovenous hemofiltration with regional citrate anticoagulation goal of the study: the aim of our study was to compare the replacement fluids (rf) phoxilium ( mmol/ l hco -) and biphozyl ( mmol/ l hco -) during continuous renal replacement therapy (cvvh) with regional citrate anticoagulation (rca) in alkalotic critically ill women and men. it was hypothesized that the hco -(hypothesis h ), base excess (be) (h ) and ph (h ) levels as well as the death rate at days (h ) dif-goal of the study: neither the feasibility nor the cardiodepressive and vasodepressive effects of isoflurane sedation in patients undergoing venoarterial extracorporeal membrane oxygenation (va-ecmo) treatment for cardiogenic shock have been investigated. as the vast majority of patients with severe cardiogenic shock treated with va-ecmo are unconscious and mechanically ventilated, the question arises to what extent a volatile sedation strategy using isoflurane is feasible in these patients, impacts the ventilation duration and intensive care unit (icu) stay, influences catecholamine dosages and va-ecmo flow support, and impacts treatment costs. methods: a total of cardiogenic shock patients with va-ecmo treatment under sedation with volatile isoflurane on our cardiac icu were enrolled in this retrospective single center study and were matched by propensity score in a : ratio with intravenously (iv) sedated patients. results and discussion: in this study patients in our registry treated with va-ecmo were sedated with isoflurane. the mean age of the patients was . ± . years for conventional sedation and . ± . years for isoflurane sedation (p = . ). administration of isoflurane was associated with lower iv sedative drug use during va-ecmo treatment ( % versus %, p = . ). mean systolic arterial pressure was similar ( . ± . mmhg versus . ± . mmhg, p = . ), but mean heart rate was significantly higher in the conventional sedation group in contrast to the isoflurane group ( . ± . /min versus . ± . /min; p = . ). importantly, catecholamine dose, va-ecmo blood flow and va-ecmo gas flow during the first days, ventilation time of survivors ( ± h versus ± h, p = . ), bleeding complications at least classified as bar-c a or higher ( . % versus . %, p = . ) and -day mortality ( . % versus . %, p = . ) were similar in both groups. the overall sedation cost per patient was significantly lower in the conventional group in comparison to the isoflurane group ( ± € versus ± €, p < . ). conclusion: volatile sedation with isoflurane is feasible, albeit with higher costs, in patients with cardiogenic shock and va-ecmo treatment and was not associated with higher catecholamine dosage and ecmo flow rate compared to iv sedation. background: acute kidney injury (aki) is a major problem in critically ill patients admitted to an intensive care unit (icu) causing both high mortality and morbidity. the aim of this study was to explore sex differences in critically ill patients admitted to an icu who had at least one episode of aki methods: all patients admitted to the icu of the university hospital innsbruck between -january and december were eligible for inclusion, if they developed at least one aki episode after icu admission. severity of aki was categorized according to kdigo methods: this retrospective study evaluated intensive care unit patients who underwent cvvh with rca between and . patients were found eligible for inclusion if they were ) aged ≥ years, ) admitted to icu, had ) the indications for cvvh as determined by the attending physician, ) a change of rf from phoxilium® to biphozyl® based on a persistent blood hco -concentration ≥ mmol/ l. patients were excluded in case of cvvh duration less than h and < h of cvvh treatment duration with phoxilium® as well as biphozyl®. overall targeted observation period including data collection was ± h from the switch of the rf. mann-whitney u-test and student's t-test was used to test h - , kaplan-meier method and logrank test was used for h . all tests -sided. results: in this study of cvvh-rca patients were eligible for analysis. of these ( %) were women (mean age years, height cm, median weight kg, bmi ) and ( %) men (mean age years, height cm, median weight kg, bmi ). during therapy with phoxilium hco -(p = . , h ) and be (p = . , h ) levels differed significantly (p < . ) between women and men, whereas ph (p = . , h ) did not. during therapy with biphozyl hco -(p = . , h ), be (p = . , h ) and ph (p = . , h ) did not differ significantly between women and men. mortality at days (p = . , h ) showed no significant difference between women and men (. fig. ) . conclusions: we found significant differences for hco -and be levels during therapy with phoxilium in alkalotic critically ill women and men, without an effect based on the volume of distribution. since no significant differences between women and men were found during therapy with biphozyl, this possibly indicates that rf with lower hco -concentrations may be beneficial for both sexes; however, we did not find significant differences in mortality. further research is warranted. fig. ( zu "high to low bicarbonate replacement fluid switch in alkalotic patients during continuous venovenous hemofiltration with regional citrate anticoagulation-a retrospective single centre analysis") trends of hco -, be, paco and ph over h before and after switching (t ) the replacement fluid from phoxilium® to biphozyl® methods: this was a post hoc analysis of patients ( female and male) from a prospective study, which investigated the potential influence of altered ca on the incidence of postoperative cognitive disorders (pocd) after major noncardiac surgery with the patient under general anesthesia. patients enrolled in this study were aged years or older and had no history of cerebrovascular or neurodegenerative disease. the ca monitoring was performed using continuous measurement of the cerebral oximetry index (cox) from incision to closure, where cox represents the moving correlation coefficient between near infrared spectroscopy (nirs) based measurement of regional cerebral oxygen saturation and mean arterial blood pressure (map). for data processing and cox calculation the icm+ software (university of cambridge, cambridge, uk) was used. a cox < . indicated intact ca, whereas a cox ≥ . indicated impaired ca and represents an increasing correlation between cbf and map. the association of gender with intraoperative cox and variables that were considered clinically relevant were analyzed with multivariate analysis. results: the time with cox ≥ . was significantly higher in male patients (males, . %, iqr . - . ); females, . %, iqr . - . , p = . ). average cox during the monitored time period was also higher in men (males, . , iqr . - . ); females, . , iqr . - . , p = . ). male gender was significantly associated with impaired ca in the multivariable analysis (b = - . , % ci: - . ;- . , p = . ). interestingly, there were no significant differences in average map, maximum map and minimum map between men and women. conclusion: women demonstrated better intraoperative ca at the same intraoperative map levels as men. our findings underline the importance of individualized blood pressure targets that may be sex-dependent. future clinical studies investigating the impact of our findings on perioperative neurological outcome are urgently needed. c (mean . ± . vs. . ± . ; p < . ). glomerular filtration rates (gfr) also showed significant differences between women and men when derived from creatinine (mean . ± . vs. . ± . ; p < . ) and from cystatin c (mean . ± . vs. . ± . ; p < . ). conclusion: while most assessed parameters showed no significant differences between women and men, both maximum creatinine and maximum cystatin c and their correspondingly minimum gfrs were significantly different between both sexes. this is an important finding, since the same creatinine criteria are considered for staging of aki, independent of possible influencing factors on creatinine, such as muscle mass. background: cerebral autoregulation (ca) is a mechanism that keeps cerebral blood flow (cbf) constant over a wide range of blood pressures, thereby ensuring the high metabolic demand of the brain [ , ] . previous studies have shown better cerebrovascular reactivity, and higher blood flow velocities in women under various conditions [ ] [ ] [ ] ; however, sex-related differences in ca in the perioperative setting are widely unexplored despite their potential impact on an individualized hemodynamic management. therefore, this study aimed to investigate sex-related differences in ca in patients undergoing major noncardiac surgery with the patient under general anesthesia. Üblicherweise erfolgt eine lagekontrolle mittels röntgen-thorax sowie ekg-ableitung, doch auch hier kann eine fehlerhafte lage nicht ausgeschlossen werden [ ] . die komplikationsraten können durch sonographisch gesteuerte punktion deutlich ( , % vs. , %) reduziert werden, auch eine sonographische lagekontrolle des seldinger-drahtes und des katheters ist so möglich [ ] . objective: percutaneous dilatational tracheotomy has become a routine procedure in intensive care units (icus); however, given the high and steadily growing number of patients receiving anticoagulation, dual antiplatelet therapy, or even a combination of both (also known as triple therapy), there are concerns about the safety of the procedure, in particular for critically ill patients with a high risk of bleeding. in this retrospective study, we investigated whether percutaneous dilatational tracheotomy in this high-risk population was associated with elevated procedural complications. design: retrospective single center study with analysis of all percutaneous dilatational tracheotomies performed in our cardiac icu from january to may . setting: munich university hospital cardiac icu. patients and interventions: a total of patients who underwent percutaneous dilatational tracheotomy according to the ciaglia technique with accompanying bronchoscopy in our cardiac icu from january to may were included. patients were stratified into clinically relevant risk groups based on anticoagulation and antiplatelet therapy considering regulation of cerebral autoregulation by carbon dioxide cerebral blood flow autoregulation and dysautoregulation sex dependency of cerebrovascular co reactivity in normal subjects influence of biological factors on changes in mean cerebral blood flow velocity in normal ageing: a transcranial doppler study elderly women regulate brain blood flow better than men do seltene ursache zerebraler ischämien: intraarterielle fehllage eines zvk -ein fallbericht abb. a röntgen-thorax nach zvk-anlage; zvk-spitze: roter pfeil. b sonographie der halsgefäße rechts nach Übernahme; zvk: roter pfeil standard laboratory coagulation parameters, i. e. activated partial thromboplastin time, international normalized ratio, and platelet count with differentiated analysis of procedure-related complications in each risk group until hospital discharge. measurements and main results: a total of patients who underwent percutaneous dilatational tracheotomy were included and assigned to clinically relevant treatment groups: iv unfractionated heparin (prophylactic dosage, n = ), iv unfractionated heparin (therapeutic dosage, n = ), aspirin and iv unfractionated heparin (therapeutic dosage, n = ), dual antiplatelet therapy with iv unfractionated heparin (prophylactic dosage, n = ), and dual antiplatelet therapy with iv unfractionated heparin (therapeutic dosage, n = ). bleedings without surgical intervention or blood transfusion was documented in three patients in the whole cohort, but no bleeding occurred in the triple therapy group. these were exclusively caused by skin bleeding at the immediate puncture site, each of which could be easily treated with one or two single stitches. there were no severe bleeding complications or potentially life-threatening procedure-related complications. additionally, the rate of complications in patients with elevated body mass index was not increased. conclusions: bronchoscopy-guided percutaneous dilatational tracheotomy according to the ciaglia technique with careful consideration of all potential indications and contraindications may be a safe and low-complication procedure for airway management, even in patients receiving dual antiplatelet therapy and therapeutic anticoagulation simultaneously in our cohort with a high risk of bleeding. interdisziplinäre operative intensivstation, klinik für anästhesiologie, intensivmedizin und schmerztherapie, universitätsklinikum des saarlandes, homburg/saar, deutschlandwir berichten über eine -jährige zeugin jehovas, die nach spontanabort in der . schwangerschaftswoche ein akutes nierenversagen und eine schwere anämie bedingt durch blutverlust und hämolyse erlitt. trotz umsetzung aller empfehlungen des "patient blood management" fiel der hämoglobinwert (hb) kontinuierlich ab. an tag wurde sie bei hb , g/ dl plötzlich bewusstlos und musste intubiert und beatmet werden. wegen organprotektiver effekte und der guten steuerbarkeit wurde sie inhalativ mit isofluran sediert. isofluran ermöglichte jeweils eine rasche neurologische beurteilbarkeit in sedierungsfenstern sowie eine regelmäßige, ruhige spontanatmung bei tiefer sedierung mit reduziertem sauerstoffverbrauch. als ausdruck einer posthypoxischen enzephalopathie zeigte sie in den sedierungsfenstern krampfanfälle, die im eeg bestätigt und antikonvulsiv behandelt wurden. bei hb , g/dl erhielt sie infusionsbeutel mit polymerisiertem bovinem hämoglobin (hemopure, hbo therapeutics llc, souderton, pa, usa), wegen der kurzen halbwertszeit mehrmals wiederholt an den folgetagen. eine beachtliche methämoglobinämie wurde festgestellt. auch nach abzug des met-hb zeigte das gesamt-hb anstiege um , - , g/dl nach den gaben. die sauerstofftransportkapazität konnte damit initial um % gesteigert werden. es kam zu einer vollständigen neurologischen erholung, und die patientin wurde schließlich vom respirator entwöhnt, jedoch weiterhin dialysepflichtig nach tagen in eine andere klink verlegt. schlussfolgerung: wenn die gabe von fremdblut keine option darstellt, kann durch gabe von polymerisiertem bovinem hämoglobin als ultima-ratio-therapie die sauerstofftransportkapazität vorübergehend erhöht werden. eine inhalative sedierung mit isofluran zur senkung des sauerstoffverbrauchs. key: cord- -li s uk authors: gimeno-costa, ricardo; barrios, marcos; heredia, tomas; garcía, carmen; de hevia, luis title: insuficiencia respiratoria covid- : soporte con ecmo para niÑos y adultos jÓvenes date: - - journal: an pediatr (barc) doi: . /j.anpedi. . . sha: doc_id: cord_uid: li s uk nan el sars-cov- afecta principalmente a adultos, y en ellos se produce el mayor número de ingresos en uci y la mayor mortalidad . aunque en niños la enfermedad se describe como menos grave y con un tiempo de recuperación más corto , presentamos el caso de una paciente de años, sana y sin contactos conocidos con covid- , que sufrió una neumonía grave por sars-cov- que requirió ecmo veno-venosa y que se ha recuperado por completo. la enferma acudió a urgencias del hospital de su departamento de salud por presentar tos y fiebre persistente durante días. la radiografía de tórax mostró una neumonía (figura a), e ingresó en la sala de hospitalización. a las horas del ingreso se constató la positividad de la hidroxicloroquina (hasta días) azitromicina (hasta días) e interferón β- b (hasta días). ese mismo día empeoró, con taquicardia, taquipnea, disnea, fiebre ( ´ ºc) y sao de % ( l/min de oxígeno suplementario). fue trasladada a uci, requiriendo de inmediato intubación tras el implante fue trasladada a la uci del hospital de referencia. a su llegada, el pulso era de latidos/min y la presión arterial / mmhg con noradrenalina a , mcg/kg/min. fue ventilada con un volumen corriente de ml/kg peso, fio % y peep cmh o. flujo sanguíneo inicial de la ecmo de , l/min con fio % (a l/min). destacaba una linfopenia, una marcada elevación de interleucina- , proteína c reactiva, ferritina y d-dimeros, con troponina negativa (tabla ). al ingreso en nuestra uci iniciamos tocilizumab ( mg primera dosis y mg horas después), metilprednisolona ( mg/kg/ horas, dosis) y cambiamos el tratamiento antiviral a remdesivir ( mg primera dosis y mg/ horas, días). la evolución posterior fue favorable. las citoquinas proinflamatorias disminuyeron y mejoró la función pulmonar: aumentó la relación pao :fio y mejoró la compliance dinámica con menor peep (tabla ). después de horas pudo retirarse la ecmo y ser extubada. tras la ecmo debe considerarse como una terapia de rescate en casos refractarios a la ventilación mecánica convencional, ventilación en prono y/o a maniobras de reclutamiento . la tasa de utilización de la ecmo durante la pandemia covid- es del , - % del total de los pacientes ingresados. en europa, hasta el de mayo de , . pacientes adultos han necesitado soporte ecmo . aunque se han descrito casos de neumonía por sars cov- en neonatos , niños y adultos jóvenes , su evolución ha sido, generalmente, favorable, siendo marginal la necesidad de apoyo extracorpóreo. nuestra paciente sufrió una neumonía grave, refractaria a la terapia convencional y requirió ecmo. un escaso número de enfermos están incluidos en el registro europeo de ecmo neonatal-pediátrico (entre ellos nuestra paciente) . los pacientes covid- adultos necesitan entre y días de soporte extracorpóreo para recuperarse. en este caso, la ecmo durante días fue suficiente para mantener la oxigenación y permitió realizar una ventilación ultra-protectora hasta que la respuesta inflamatoria disminuyó. no detectamos efectos adversos en la combinación de los tratamientos antivirales y antiinflamatorios utilizados. tampoco tuvimos que modificar su posología, por lo que consideramos que no ha habido alteraciones farmacocinéticas relacionadas con el circuito o con la membrana extracorpórea. muchos artículos publicados durante la actual pandemia muestran el curso clínico de pacientes que todavía están en uci (incluso en ecmo). la nuestra es la primera paciente pediátrica sometida a ecmo veno-venoso totalmente recuperada y dada de alta a su domicilio sin secuelas. la terapia extracorpórea en su caso se ha mostrado eficaz y segura (incluyendo un traslado inter-hospitalario), por lo es una opción terapéutica para niños y adolescentes en el clinical characteristics of coronavirus disease in china sars-cov- infection in children planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases european survey on ecmo in covid- pts at / / primer caso de infección neonatal por sars-cov- en españa coronavirus disease in critically ill children: a narrative review of the literature. pediatr crit care med figura : radiografía simple de tórax a: radiografía de tórax en urgencias del hospital departamental de tórax al ingreso en la uci del hospital departamental (prono) c: radiografía de tórax al ingreso en la uci tras el traslado inter-hospitalario al hospital de referencia d: radiografía de tórax en la planta del hospital de referencia (día del alta hospitalaria) key: cord- -kuvnwdn authors: ikegami, saya; jitsuiki, kei; nagasawa, hiroki; nishio, ryota; yanagawa, youichi title: suspected virus-inducing severe acute respiratory distress syndrome treated by multimodal therapy including extracorporeal membrane oxygenation and immune modulation therapy date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: kuvnwdn a -year-old man who had been feeling general fatigue was found in an unconscious state on the same day. he had no remarkable medical history. on arrival at the hospital, his glasgow coma scale was e v m ; he had tachycardia and hypertension, was afebrile, and in a severe hypoxic state. his pao( )/fio( ) (p/f) was under , even with tracheal intubation with % oxygen. chest x-ray and ct revealed a bilateral ground-glass appearance with consolidation. cardiac echo initially showed hyper-dynamic wall motion. the main results of a blood analysis suggested an acute inflammatory reaction, rhabdomyolysis, and pancreatitis. the microscopic findings of sputum and a rapid test for bacterial and viral infections were all negative. as he showed deterioration of p/f, venovenous extracorporeal membrane oxygenation (ecmo) was started. he also showed hypotension and therefore underwent vasopressor and steroid administration. due to concerns of pneumonia, he received meropenem and azithromycin in addition to the infusion of γ-globulin and glycyrrhizin. the results of a covid- test, culture of sputum, and collagen disease test were all negative. the serum virus neutralization assay as a serological test for coxsackievirus b showed a four-fold increase in titer. the multimodal therapy mentioned above resulted in the improvement of his general condition, including acute respiratory distress syndrome (ards). in this report, we discuss the benefits of ecmo and immune modulation therapy in the treatment of severe ards. acute respiratory distress syndrome (ards) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of non-cardiogenic pulmonary edema, hypoxemia, and the need for mechanical ventilation [ ] [ ] [ ] [ ] . the pathology of ards is diffuse alveolar damage, such as the rapid development of capillary congestion, atelectasis, intraalveolar hemorrhaging, and alveolar edema, followed days later by hyaline-membrane formation, epithelial-cell hyperplasia, and interstitial edema [ ] . ards occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents, or severe trauma and is present in roughly % of all patients in intensive-care units worldwide [ ] . although much progress has been made in improving supportive care for ards, effective pharmacological therapies have not yet been identified, and mortality remains high at %- % in most studies [ ] . we report a case of suspected virus-inducing severe ards treated by multimodal therapy including extracorporeal membrane oxygenation (ecmo) and immune modulation therapy that led to a favorable outcome for the patient. a -year-old man felt generalized fatigue and took the day off from work. his son called him on the same day, but he did not respond. when the son visited his house, he found the patient unconscious and called an ambulance. he had no remarkable medical history. he was a neversmoker and drank g of ethanol per day. he worked as a truck driver and lived with his only son after his divorce. his work zone was not located in any of the districts that were reported to have covid- infections. when the emergency medical technicians checked him, he had a tonic convulsive posture with severe hypoxia, and he was transported to our hospital under bag-valve-mask ventilation with high-concentration oxygen. on arrival, his glasgow coma scale was e v m . a physical examination revealed the following findings: blood pressure of / mmhg; heart rate of beats per minute; a respiratory rate of breaths per minute; spo of % under room l per minute of oxygen; and body temperature of . °c. a venous route was immediately secured, followed by endotracheal intubation. an arterial gas analysis revealed the following findings: ph: . ; pco : . mmhg; po : . mmhg; base excess - . mmol/l; and lactate: mmol/l. electrocardiography revealed sinus tachycardia. a chest x-ray revealed a bilateral ground-glass appearance ( figure ). cardiac echo showed hyper-dynamic left-ventricular wall motion. whole-body ct revealed a bilateral ground-glass appearance in the ventral lung fields and bilateral consolidation in the dorsal lung fields ( figure ). the image shows a bilateral ground-glass appearance in the ventral lung fields (arrow) and bilateral consolidation in the dorsal lung fields (asterisks) the pancreas was normal. the main results of a blood analysis were as follows: wbc count: , /μl (neutrophil %, lymphocyte %, monocyte %); hemoglobin: . g/dl; platelet count: . × /μl; total protein: . g/dl; albumin: . g/dl; glucose: mg/dl; hba c: . %; total bilirubin: . mg/dl; aspartate aminotransferase: iu/l; alanine aminotransferase: iu/l; lactate dehydrogenase: , iu/l; blood urea nitrogen: . mg/dl; creatinine: . mg/dl; amylase: (pancreas %) iu/l; creatine phosphokinase (ck): , iu/l; sodium: meq/l; potassium: . meq/l; chloride: meq/l; brain natriuretic peptide: . pg/ml; c-reactive protein: . mg/dl: prothrombin time international normalized ratio: . ; activated partial thromboplastin time: . ( . ) seconds; fibrinogen: mg/dl; ddimer: . μg/ml; human immunodeficiency virus (hiv) antibody: negative; pneumococcal urinary antigen test: negative; legionella urinary antigen test: negative; rapid influenza diagnostic test: negative; microscopic finding of sputum: negative: and urine drug screening test: negative. later, β-d glucan, rheumatoid factor, and anti-neutrophil cytoplasmic antibody were all found to be negative. he received a tentative diagnosis of pneumonia of unknown causes accompanying severe ards, rhabdomyolysis, and pancreatitis. as he showed deterioration of pao [pao /fio (p/f) = ] and a murray score of . , he underwent mechanical ventilation under . fio and cmh o with positive end-expiratory pressure (peep) and received indwelling venovenous ecmo (mera centrifugal blood pump system has-cfp; mera nhp exelung nsh-r hpo- wh-c; senko medical instruments, tokyo, japan) with the right jugular vein (return side, fr) and right femoral vein (drainage side, fr) as the exit. as this event occurred during the night shift, we did not attempt supine therapy before introducing venovenous ecmo. he also showed hypotension and therefore underwent infusion of noradrenalin followed by vasopressin and mg of hydrocortisone. due to concerns of pneumonia, he received . g of meropenem and mg of azithromycin in addition to an infusion of g of γ-globulin and ml of glycyrrhizin as antibacterial and antivirus treatments respectively. after the induction of ecmo, the mode of mechanical ventilation was changed to a lung rest setting ( . fio and cmh o with peep). additional cardiac echo showed diffuse hypokinesis with a % ejection fraction, and troponin t became positive [ pg/ml (normal range: < pg/ml)] on the first hospital day, and so he was diagnosed with myocarditis as a complication. on the second day, his blood pressure increased, resulting in a reduction in the vasopressor administration. his p/f remained under . on the third day, inflammatory data remained high, and hence azithromycin was replaced with levofloxacin. however, this led to skin reddening and he was switched back to azithromycin. a complication of anemia, thrombocytopenia, and coagulopathy required blood transfusion. a polymerase chain reaction (pcr) test for covid- using sputum through the endotracheal tube without bronchoalveolar lavage (performed twice) and initial cultures of sputum, urine, and blood were all negative. on the fifth day, the inflammatory data remained moderate, and hence meropenem was replaced with linezolid and piperacillin/tazobactam. on the same day, in an attempt to withdraw ecmo, the mechanical ventilation setting was changed from to cmh o for peep and from . to . for fio . this resulted in the p/f increasing to over . after the circulation flow of ecmo was reduced from to l/minute, the p/f remained over ; hence ecmo was ceased, and the cannulations were removed (figure ). as the patient was thought to require long-term mechanical ventilation, he underwent tracheostomy on the eighth hospital day. sedative administration was ceased, and a negative water balance was targeted by limiting the infusion volume and the use of diuretics. he showed a transient decrease in his p/f by the formation of atelectasis due to bloody sputum; however, the average p/f improved day by day. on the th hospital day, his p/f exceeded under cmh o for peep and . fio ; hence mechanical ventilation was ceased (figure ). the patient was managed by extracorporeal membrane oxygenation and mechanical ventilation with the lung rest setting on the third day and was withdrawn from mechanical ventilation on the th day day (left) shows bilateral ground-glass appearances. day (middle) shows the deterioration of bilateral radiolucency. day (right) shows clear lung fields he recovered his ability to excrete sputum by himself, and tracheal cannulation was removed on the th hospital day. even after ceasing all drugs for lung and inflammation, his pneumonia, rhabdomyolysis, and pancreatitis did not recur. he was discharged on the nd day on foot. the troponin t level remained high ( pg/ml) even after the ck level normalized, so he was followed up as an outpatient. the serum virus neutralization assay performed as a serological test using pair serum samples with a more than two-week interval for coxsackievirus b showed a four-fold increase in titer (from x to x ). finally, the troponin t level returned to the normal range and showed no subsequent complications. risk factors of direct lung injury involving ards include pneumonia (bacterial, viral, fungal, or opportunistic), aspiration of gastric contents, pulmonary contusion, inhalation injury, and near-drowning, while those of indirect lung injury involving ards include sepsis (nonpulmonary source), non-thoracic trauma or hemorrhagic shock, pancreatitis, major burn injury, drug overdose, transfusion of blood products, cardiopulmonary bypass, reperfusion edema after lung transplantation, and embolectomy [ , ] . the risk factor in the present case was unspecified pneumonia, and an unspecified virus was considered the most likely cause based on the negative results of all cultures, β-d glucan, and rapid test for bacteria and influenza. concerning covid- , while an outbreak had been reported in tokyo at the time, our patient did not live in a covid- -infected district; in addition, two tests for covid- were negative, and ct showed subpleural sparing with a ground-glass appearance, which is not common for covid- . accordingly, the possibility of covid- -related pneumonia was considered to be low. based on our investigations for virus infection, we suspect that coxsackievirus b might have been the responsible virus. however, there are few reports concerning coxsackievirus b infection with pulmonary involvement, and there have been no reports of ards induced by coxsackievirus b [ ] . accordingly, this might be the first case report of severe ards in an adult induced by coxsackievirus b infection. as we did not perform a direct examination of a pulmonary specimen, the possibility of co-infection with multiple viruses or reactivation of coxsackievirus b cannot be excluded. there are two main treatments for ards: treating the main cause of ards or offering supportive therapy for the severely injured lungs. supportive therapy involves oxygen and mechanical ventilation. according to the berlin definition, severe ards requires mechanical ventilation with a high peep and a high concentration of oxygen. when conventional mechanical ventilation fails to improve the arterial oxygenation and/or eliminate carbon dioxide, ecmo is indicated. another indication is circulatory and/or cardiac failure. the conventional ventilation mode can cause ventilator-induced lung injury, such as volutrauma, atelectrauma, and/or biotrauma. in addition, the continuous inspiration of high-concentration oxygen can also injure the lungs. the induction of ecmo helps avoid such mechanical-and oxygen-induced lung injuries by using the lung rest setting, allowing patients time to recover from their lung injuries [ ] [ ] [ ] . as the present case also showed marked hypoxia despite mechanical ventilation with a high concentration of oxygen and high peep, ecmo was introduced, and the lung rest setting was selected. the severity of ards depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, and the repertoire of specific immune cells that control the substances. therefore, treatment with systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the early stage of ards [ ] . the results from clinical trials have often been controversial; however, the administration of steroids may shorten the duration of mechanical ventilation, duration of hospitalization, and improve oxygenation, probably because of the wide spectrum of potentially desirable effects, including antiinflammatory, antioxidant, pulmonary vasodilator, and anti-edematous [ , , ] . lee et al. noted that early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) along with antibiotics or antivirals could halt the progression of pneumonia and induce a rapid recovery of pulmonary lesions in patients with ards [ ] . furthermore, macrolides also induce a broad range of immunological mechanisms that result in immunomodulatory effects; hence macrolide therapy can also help reduce mortality in patients with ards [ ] . accordingly, the variety of supportive therapies offered for ards may explain the favorable outcome in the present case. viral pneumonia was thought to be the most likely cause of ards in the present case. respiratory viruses are a common cause of severe pneumonia and ards in adults [ , ] . initially, the present case was suspected of having covid- infection, but this diagnosis was not supported by pcr performed twice. the percentage of patients with ards for which no causative organism has been identified despite bronchoalveolar lavage or pcr testing remains high (> - %) [ ] . although antiviral therapy is available for some respiratory viral infections, most viruses do not have any specific treatment. one of the antivirus therapies used in the present case was glycyrrhizin. glycyrrhiza glabra roots contain glycyrrhizic acid (glycyrrhizin), which is effective against viruses [ ] . glycyrrhizin inhibits the growth and cytopathology of several unrelated dna and rna viruses while not affecting human cell activity or their ability to replicate [ ] . glycyrrhizin is therefore now applied in the treatment of a variety of viral infections [ ] . traditional chinese medicines such as glycyrrhizin may also be effective against covid- infection [ ] . in addition, macrolide and γ-globulin can also exert an antiviral effect [ ] . these unspecific antiviral therapies may be useful treatments for the main cause of ards, which may have resulted in the favorable outcome obtained in the present case. the present case showed pneumonia, pancreatitis, rhabdomyolysis, and myocarditis. the involvement of two pathogens (salmonella typhi and mycoplasma) that have been reported to accompany such complications was not found in the present case [ , ] . however, cases of pneumonia, rhabdomyolysis, myocarditis, and pancreatitis induced by coxsackievirus b have been reported [ ] [ ] . accordingly, this virus may have been the causative pathogen of these complications in the present case. we presented a case of suspected virus-inducing severe ards that was treated by multimodal therapy including ecmo and immune modulation therapy. the wide range of supportive therapies and unspecific antiviral therapies offered for ards may have resulted in the favorable outcome obtained in the present case. human subjects: consent was obtained by all participants in this study. the review board of juntendo shizuoka hospital issued approval . this case study was approved by the review board of juntendo shizuoka hospital. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: this work was supported in part by a grant-in-aid for special research in subsidies for ordinary expenses of private schools from the promotion and mutual aid corporation for private schools of japan. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. acute respiratory distress syndrome: the ikegami et al berlin definition acute respiratory distress syndrome definition, causes, and pathophysiology acute respiratory distress syndrome acute respiratory distress syndrome coxsackie b pneumonia in an adult extracorporeal life support for adults with respiratory failure and related indications: a review extracorporeal membrane oxygenation for acute respiratory distress syndrome: eolia and beyond referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza a(h n ) pneumonia, acute respiratory distress syndrome, and early immune-modulator therapy corticosteroids in acute lung injury: the dilemma continues the immunomodulatory effects of macrolidesa systematic review of the underlying mechanisms viral pneumonia and acute respiratory distress syndrome glycyrrhizic acid inhibits virus growth and inactivates virus particles research progress of glycyrrhizic acid on antiviral activity traditional chinese medicine for covid- treatment therapeutic control of viral infections: chemotherapy, interferon and gamma globulin salmonella typhi infection complicated by rhabdomyolysis, pancreatitis and polyneuropathy rhabdomyolysis associated with infection by mycoplasma pneumoniae: a case report tumor necrosis factor and coxsackie b rhabdomyolysis development of potential antiviral strategy against coxsackievirus b key: cord- -y lvewlz authors: zeng, yingchun; cai, zhongxiang; xianyu, yunyan; yang, bing xiang; song, ting; yan, qiaoyuan title: prognosis when using extracorporeal membrane oxygenation (ecmo) for critically ill covid- patients in china: a retrospective case series date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: y lvewlz nan prognosis when using extracorporeal membrane oxygenation (ecmo) for critically ill covid- patients in china: a retrospective case series yingchun zeng † , zhongxiang cai † , yunyan xianyu † , bing xiang yang * , ting song * and qiaoyuan yan * the world health organization (who) has characterized the disease, coronavirus disease (covid- ), as a pandemic on march , (www.who.int). as of march , the who had recorded a total of , confirmed covid- cases, with death cases (www.who.int). while the cumulative mortality of covid- is . %, covid- has resulted in more death cases than sars and mers combined [ ] . within china, a total of , cases are confirmed, with severe cases in mainland china (www.nhc. gov.cn). in severe cases of covid- , patients experience rapid disease progression and can quickly progress to acute respiratory distress syndrome (ards) [ ] . based on this, when covd- patients develop ards and mechanical ventilation cannot be improved, extracorporeal membrane oxygenation (ecmo) can be used [ ] . as mortality rates among critically ill covid- patients can be as high as . % [ ] , ecmo may play a role in reducing mortality rates [ ] . the indications of using ecmo are "for patients with severe ards, it is recommended to perform lung expansion. in the case of adequate human resources, prone positioning should be recommended for at least hours per day for protective ventilation. if severe respiratory failure persisted, then ecmo should be started as soon as possible." [ ] worldwide data on prognosis when using ecmo to treat critically ill patients with covid- infection are not available, and whether ecmo plays a role in reducing patient mortality rates is currently unknown. this research letter provides the first evidence of prognosis in treating critically ill covid- patients with ecmo in china. these preliminary data were collected from two medical centers of wuhan, china (table ) . these data could be of considerable value in judging whether ecmo should be recommended as a salvage therapy for critically ill covid- patients. to date, the role of ecmo in the management of covid- is unpromising. nearly half of the patients treated with ecmo died from septic shock and multiple organ failure. the observed late complications included bleeding and infection. while the world health organization (who) interim guidelines and china's national interim guidelines for the diagnosis and treatment of covid- infection (sixth version) have made general recommendations for the use of ecmo for ards and critical covid- infection [ , ] , the preliminary evidence available in mainland china does not support this general recommendation. certainly, understanding the risk-to-benefit ratio of performing ecmo on critically ill covid- patients is dynamic as the course of this novel disease unfolds. the chinese government covers all costs to treat patients with the covid- infection, so the cost analysis of ecmo is to date unavailable in mainland china. however, an average ecmo procedure in the usa costs $ , usd, indicating that ecmo is a highly resource-demanding procedure [ ] . therefore, a further, larger sample size study and a comprehensive analysis of the medical value of using ecmo on covid- patients are urgently required. based on the two cohort case series in this study, nearly half of the critically ill covid- patients with ecmo were dying from septic shock and multiple organ failure. as anticipated by maclaren et al. [ ] , covid- is a pandemic; all healthcare resources are stretched so that ecmo is not a therapy to be rushed to the frontline. therefore, interim treatment guidelines [ , ] of recommending ecmo for critically ill covid- patients should be taken cautiously. coronavirus: covid- has killed more people than sars and mers combined, despite lower case fatality rate chinese expert consensus on supportive treatment of extracorporeal membrane oxygenation novel coronavirus pneumonia preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study preparing for covid- : early experience from an intensive care unit in singapore diagnosis and treatment guideline for covid- infection cost of extracorporeal membrane oxygenation: evidence from the rikshospitalet university hospital publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations thanks to all the participants involved in this study. authors' contributions yz, manuscript writing; zc, yxy, bxy, data collection and analysis; ts, qyy, manuscript revision. the authors read and approved the final manuscript. none. the datasets used in the present study are available from the first author and corresponding authors on reasonable request. this study was approved by the institutional review board of wuhan university school of health sciences. informed consent was waived, as this study was conducted during a public health outbreak. not applicable. none. key: cord- - twwcp authors: combes, alain; peek, giles j.; hajage, david; hardy, pollyanna; abrams, darryl; schmidt, matthieu; dechartres, agnès; elbourne, diana title: ecmo for severe ards: systematic review and individual patient data meta-analysis date: - - journal: intensive care med doi: . /s - - - sha: doc_id: cord_uid: twwcp purpose: to assess the effect of venovenous extracorporeal membrane oxygenation (ecmo) compared to conventional management in patients with severe acute respiratory distress syndrome (ards). methods: we conducted a systematic review and individual patient data meta-analysis of randomised controlled trials (rcts) performed after jan , comparing ecmo to conventional management in patients with severe ards. the primary outcome was -day mortality. primary analysis was by intent-to-treat. results: we identified two rcts (cesar and eolia) and combined data from patients. on day , of the ( %) ecmo-group and of the ( %) control group patients had died (relative risk (rr), . , % confidence interval (ci) . – . ; p = . ; i( ) = %). in the per-protocol and as-treated analyses the rrs were . ( % ci . – . ) and . ( % ci . – . ), respectively. rescue ecmo was used for ( %) of the control patients ( in eolia and in cesar). the rr of -day treatment failure, defined as death for the ecmo-group and death or crossover to ecmo for the control group was . ( % ci . – . ; i( ) = %). patients randomised to ecmo had more days alive out of the icu and without respiratory, cardiovascular, renal and neurological failure. the only significant treatment-covariate interaction in subgroups was lower mortality with ecmo in patients with two or less organs failing at randomization. conclusions: in this meta-analysis of individual patient data in severe ards, -day mortality was significantly lowered by ecmo compared with conventional management. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. ventilatory management of patients with severe acute respiratory distress syndrome (ards) has improved over the last decades with a strategy combining low tidal volume (vt) ventilation [ ] , high positive end-expiratory pressure (peep) [ , ] , neuromuscular blocking agents [ ] and prone positioning [ ] . however, ventilator-induced lung injury (vili) may persist in these patients since a recent and large epidemiological study showed that their hospital mortality was still % [ ] . recently, even higher mortality was reported for patients with severe acute respiratory syndrome coronavirus (sars-cov- ) infection who needed invasive mechanical ventilation [ ] [ ] [ ] . venovenous extracorporeal membrane oxygenation (ecmo) providing full blood oxygenation, co elimination and combined with more gentle ventilation has benefited from major technological advances in the last years [ , ] . in , favourable outcomes were reported in patients who received ecmo during the influenza a (h n ) pandemic [ ] [ ] [ ] . the conventional ventilator support vs extracorporeal membrane oxygenation for severe acute respiratory failure (cesar) trial [ , ] showed that transfer to an ecmo centre was associated with fewer deaths or severe disabilities at months compared with conventional mechanical ventilation ( % vs. %; p = . ), although month mortality was not significantly reduced ( % vs. %; p = . ). the more recent ecmo to rescue lung injury in severe ards (eolia) trial showed a non-statistically significant reduction in -day mortality with ecmo ( % vs. %; p = . ) [ ] . however, neither trial was separately powered to detect a - % survival benefit with ecmo. we performed a systematic review with an individual patient data meta-analysis of randomised controlled trials comparing ecmo to conventional mechanical ventilation in patients with severe ards. the primary objective was to evaluate the effect of ecmo on -day mortality. secondary objectives included the evaluation of ecmo for other clinical outcomes and in pre-specified subgroups for the primary outcome. this systematic review and meta-analysis followed the preferred reporting items for systematic reviews and meta-analyses for individual patient data (prisma-ipd checklist in etable in the supplement) and the protocol was registered in prospero (crd ) on may st . we included all randomised controlled trials (rcts) evaluating venovenous ecmo in the experimental group and conventional ventilatory management in the control group, that included patients with ards fulfilling the american-european consensus conference definition [ ] or the berlin definition for ards [ ] , and that were published or whose primary completion date was after [ , , ] . this choice was justified by the major improvements in intensive care treatments and in ecmo technology that occurred in the last two decades. additional information on selection criteria is provided in the supplement. we searched medline via pubmed, embase and the cochrane central register of controlled trials (central) from january , to september , using a search algorithm developed for the purpose of this study and adapted to each database (etable in the supplement). we also searched trial registries including clini-caltrials.gov and the international clinical trial registry platform (ictrp) for completed and ongoing trials, conference proceedings of major critical care societies and screened reference lists of identified articles as well as systematic or narrative reviews on the topic (see the supplement). selection was conducted independently by two reviewers (da and ms) on titles and abstracts first and then, on the full text. for each included rct, the corresponding author was contacted to provide fully anonymized individual patient data as well as format, coding and definition of any variables. risk of bias in each trial was evaluated by two independent reviewers (dh and ad) using the updated version of the risk-of-bias tool developed by cochrane [ ] (see the supplement). the primary endpoint was mortality days after randomisation. main secondary endpoints comprised time to death up to days after randomisation, treatment failure up to days, defined as crossover to ecmo or death for patients in the control group, and death for patients in the ecmo group, number of days alive and out-of-hospital between randomisation and day , number of days alive without mechanical ventilation, renal replacement therapy and vasopressor support between randomisation and day . other preplanned secondary outcomes comprised mortality at and days after randomisation, number of days alive and out of the icu between randomisation and day , number of days alive without respiratory failure, neurological failure, cardiovascular failure, liver failure, renal failure and coagulation failure, defined as the corresponding component sequential organ failure assessment (sofa) score greater in this meta-analysis of individual patient data in severe ards, -day mortality was significantly lowered by ecmo compared with conventional management. patients randomised to ecmo had more days alive out of the icu and without respiratory, cardiovascular, renal and neurological failure than between randomisation and day . data related to patients' management, causes of death and safety outcomes were also described (see the supplement). the statistical analysis was performed for each outcome of interest using individual patient data. an intentionto-treat analysis was used for all outcomes, whereby all patients were analysed in the groups to which they were randomised. the measures of treatment effect were risk ratios for binary outcomes, hazard ratios for time-toevent outcomes and mean differences for quantitative outcomes. the primary endpoint was defined as a binary outcome and analysed using both one-step (as primary analysis) and two-steps (as sensitivity analysis) methods [ ] . in the one-step method, we analysed both studies simultaneously to obtain the combined treatment effect with % cis and p-value using a generalized linear mixed effect model to account for the clustering of data within each trial with a random effect. in the two steps method, we first analysed separately each trial using individual patient data before combining them using a random effects meta-analysis model to account for variability between studies. a two-step method was used for all secondary outcomes. heterogeneity was evaluated with the cochran's q-test, i statistic and between study variance τ . survival curves for the time to death up to days were generated using individual patient data and the kaplan-meier method. we conducted sensitivity analyses for the primary outcome in different populations (per-protocol, as-treated). the per-protocol population included all randomised patients having received the treatment attributed by randomisation (i.e., patients having received ecmo in the ecmo arm and patients not having received ecmo in the control arm). the as-treated population compared patients receiving ecmo to those who did not receive ecmo, whatever the randomisation arm. a sensitivity analysis excluding trials at high risk of bias was also planned. we explored whether the effect of ecmo on -day mortality varied according to baseline patient characteristics (see the supplement). for each subgroup, the treatment-subgroup interaction was tested in the one-step model. for quantitative baseline characteristics, we used the median values to define the subgroups. all these subgroup analyses were pre-planned. alpha risk was set at % for the primary outcome. for all secondary outcomes, we did not correct for multiple testing. as such, subgroup and sensitivity analyses should be considered as exploratory. all the analyses were performed with the use of r software version . . (r foundation). from the references identified by the search strategy, we included two randomised controlled trials fulfilling our eligibility criteria-cesar and eolia [ , ] . reasons for exclusion are reported in efig. of the supplement. the two trials provided individual patient data for all randomised patients ( overall, in cesar and in eolia), and there was no eligible trial not providing individual patient data. detailed characteristics of the two trials are reported in etable in the supplement. comparison of patient characteristics at randomisation did not show baseline imbalance between groups (table and etables and in the supplement). the main disorder leading to study entry was severe hypoxia (in % of the patients, with a mean (± sd) pao /fio of ± mm hg). the main cause of ards was pneumonia (> % of the patients) and % had or more organs failing at randomisation. of the patients randomised to the ecmo groups, ( %) received ecmo ( % and % in eolia and cesar, respectively). rescue extracorporeal gas exchange was used for ( %) of the control patients ( patients crossed over to ecmo in eolia, and to pumpless arteriovenous co removal in cesar that was a protocol violation by the conventional management team as rescue extracorporeal gas exchange was not part of the cesar trial design). risk of bias was judged low in both trials (efigure in the supplement). by day , ( %) ecmo-group and ( %) control group patients had died (relative risk, . , % confidence interval . - . ; p = . ) ( table and fig. ). results were similar in the one-step and two-steps models. there was no evidence of heterogeneity across studies (p = . , i = %, τ = . ). the hazard ratio for death within days after randomisation in the ecmo group, as compared with the control group, was . ( % ci . - . ) (fig. ) . the relative risk of treatment failure, defined as death by day for the ecmo-group and death or crossover to ecmo for the control group was . ( . - . ) ( at day post-randomisation ( -day follow-up was not available for the following outcomes in eolia), patients in the ecmo group had more days alive without vasopressors ( vs days, mean difference, days; % ci, to ), renal replacement therapy ( vs days, mean difference, days; % ci - ) and neurological failure ( vs days, mean difference, days; % ci - ) than those in the control group (table and efig. in the supplement). prone positioning and low-volume low-pressure mechanical ventilation were applied to % and % of control group patients, respectively (table ) . multiorgan failure and respiratory failure were the main causes of death in both groups (table ) , while a cannulation-related fatal complication occurred in of the patients who received ecmo. of the patients randomised to ecmo, ( %) died before ecmo could be established. additional data on secondary outcomes are provided in tables and and efig. in the supplement. the relative risks of death at day post-randomisation according to the per-protocol and as-treated analyses were . ( % ci . - . ) and . ( % ci . - . ), respectively (efig. in the supplement). the only significant treatment-covariate interaction identified in subgroup analyses was the number of organs failing at randomisation with rr = . ( % ci . - . ) among patients with - organ failures and rr = . ( % ci . - . ) among patients with or more organ failures, p = . for interaction (fig. ) . there was no evidence to suggest a differential treatment effect for any other subgroups. the summary of findings table reporting the evaluation of the quality of evidence for the seven most important outcomes is presented in etable in the supplement. the level of evidence was high for mortality at days, time to death and treatment failure. in this individual patient data meta-analysis of patients with severe ards included in the cesar [ ] and eolia [ ] randomised trials, there is strong evidence to suggest that early recourse to ecmo leads to a reduction in -day mortality and less treatment failure compared with conventional ventilatory support. patients randomised to ecmo also had more days alive out of the icu and without respiratory, cardiovascular, renal and neurological failure. the benefit of ecmo in severe ards patients has long been debated [ ] [ ] [ ] [ ] . because of highly challenging design and conduct issues, only four randomised trials of extracorporeal life support for adult patients with acute respiratory failure have been performed in the last decades [ , , , ] . our meta-analysis included only the two most recent trials (cesar [ ] and eolia [ ] ) since major advances in icu care and in ecmo techniques have occurred in the past years making the two older trials not relevant for comparison [ , , ] . in addition the two older trials did not use venovenous ecmo. one used venoarterial ecmo [ ] and one used low-flow veno-venous extracorporeal co removal [ ] . characteristics of patients included in eolia and cesar were comparable regarding ards aetiology and disease severity at randomisation. patients were enrolled early after the initiation of invasive mechanical plus-minus values are means ± sd; see etable the supplement for missing data ecmo denotes extracorporeal membrane oxygenation, ards the acute respiratory distress syndrome, pao partial pressure of arterial oxygen, fio the fraction of inspired oxygen, pao /fio the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, peep positive end-expiratory pressure missing data were < % for patients' characteristics at randomisation, except for predicted mortality, respiratory system compliance and murray score (see etable in the supplement) a number of organ failed ( - ) defined as the corresponding component sequential organ failure assessment (sofa) score > b apache (cesar) and saps (eolia) scores were both translated to predicted probability of icu mortality chest radiograph (quadrants infiltrated) . ± . . ± . ventilation and rates of control patients being proned and receiving low-volume low-pressure mechanical ventilation were high. both eolia and cesar trials showed a comparable survival benefit with ecmo, but neither was individually powered to detect a reasonable survival difference between groups. specifically, the data safety monitoring board of eolia, following pre-specified guidance using a sequential design with a two-sided triangular test based on -day mortality, recommended stopping the trial for futility after % of the maximal sample size had been enrolled, because the probability of demonstrating a % absolute risk reduction in mortality with ecmo was considered unlikely. our meta-analysis, which includes a much larger number of patients and shows higher survival with ecmo in both the intention-to-treat and per-protocol analyses provides strong evidence about the benefit of ecmo in severe ards. our results also extend the conclusions of a post-hoc bayesian analysis of eolia indicating a very high probability of ecmo success in severe ards patients, ranging from to % depending on the chosen priors [ ] . our results are consistent with two previous aggregated data meta-analyses in the field: one was a network meta-analysis considering different interventions whose impact is limited by the [ ] and the other focused on ecmo [ ] . our ipd meta-analyses goes beyond these two previous studies and provides a stronger evidence on the benefit of ecmo in ards for the following reasons. ipd meta-analyses provides a higher level of evidence than aggregated data meta-analyses, because they are independent of the quality of reporting in included studies and allow evaluation of other important outcomes such as time to death and number of days without organ failures [ , ] . in this study, we showed that, beyond mortality, duration and severity of organ failures also favoured ecmo, and these results were highly consistent between the two studies. this observation provides insights into the potential pathophysiological mechanisms of ecmoassociated benefits in severe ards [ ] . although extracorporeal gas exchange may rescue some patients dying of profound hypoxemia or in whom high pressure mechanical ventilation has become dangerous, minimization of lung stress and strain associated with positive pressure ventilation may drive most of the improved outcomes observed under ecmo [ ] . ultraprotective ventilation with very low vts, driving pressures and respiratory rates [ ] , and, therefore, minimized overall mechanical power transmitted to lung alveoli [ ] may reduce ventilator-induced lung injury, pulmonary and systemic inflammation and ultimately organ failure leading to death. these data also reinforce the recent recommendation of the world health organization (who) [ ] , and the surviving sepsis campaign [ ] to consider ecmo support in coronavirus disease (covid- )-related ards with refractory hypoxemia if lung protective mechanical ventilation was insufficient to support the patient [ ] . meta-analyses of individual patient data can also explore outcomes in important subgroups and suggest which population may derive the greatest benefit of a specific intervention, which is very limited in aggregated data meta-analyses [ ] . in this study, the mortality of patients with only one or two organs failing at randomisation was almost halved with ecmo ( % vs. %), while it was not substantially different between groups in patients with ≥ organ failures. this finding suggests that veno-venous ecmo may not be able to improve the outcomes of ards patients with severe shock and multiple organ failure. in eolia, patients with baseline pao / fio > mmhg or those enrolled due to severe respiratory acidosis and hypercapnia, seemed to derive the greatest benefit of ecmo [ ] . this analysis has several limitations. first, inclusion criteria were more stringent for the eolia trial, in which, for example, ventilator optimization (fio > %, vt at ml/kg predicted body weight and peep > cm h o) was mandatory before enrolment. however, it should be noted that baseline patient characteristics were comparable regarding ards severity at inclusion (etable in the supplement). second patient management was not similar in the two studies. in cesar, % of patients randomised to the ecmo arm did not receive ecmo and there was no standardized protocol for mechanical ventilation in the control group. conversely, in eolia, % of patients randomised to ecmo received the intervention, the mechanical ventilation strategy in the control group followed a strict protocol, and rescue ecmo was applied to % of control group patients who had developed refractory hypoxemia. however, this meta-analysis showed a significantly lower mortality with ecmo in the per-protocol analysis including only patients in whom ecmo had been initiated in the ecmo arm and patients not having ecmo in the control arm. this analysis minimizes the aforementioned management differences, since the least severe patients who did not receive ecmo after mv optimization in cesar were excluded from the ecmo arm and the most severe patients who needed rescue ecmo in eolia were excluded from the control arm. in contrast, ecmo was not associated with a mortality benefit in the as-treated population, but such an analysis strongly disadvantages the ecmo group, which includes the most severe control patients rescued by ecmo. second, this meta-analysis does not provide detailed data on ecmo-related safety endpoints, since they were not reported in cesar. death directly related to ecmo cannulation was rare in both studies and the rates of stroke and major bleeding were also low in eolia, in which a restrictive anticoagulation strategy was applied [ ] . third, no long-term outcomes beyond day post-randomisation were analysed although the cesar trial [ ] and a retrospective cohort of ards patients [ ] reported satisfactory long-term health-related quality-of-life after ecmo. fourth, only the cesar trial provided a cost-effectiveness analysis that suggested a benefit of the transfer of ards patients to a centre with an ecmo-based management protocol [ ] . our results, showing improved survival, with more days alive out of the icu and without the need for major organ support are in line with cesar's cost-effectiveness data. fifth, many conditions such as mv duration > days prior to ecmo or major comorbidities were exclusion criteria for enrolment in both cesar and eolia. the indication to initiate ecmo should, therefore, be carefully evaluated in these situations. lastly, ecmo should be used in experienced centres and only after proven conventional management of severe ards (including lung protective mechanical ventilation and prone positioning) have been applied and failed [ ] , except when hypoxemia is immediately life-threatening, or when the patient is too unstable for prone positioning [ ] . in conclusion, this meta-analysis of individual patient data of the cesar and eolia trials showed strong evidence of a clinically meaningful benefit of early ecmo in severe ards patients. another large study of ecmo appears unlikely in this setting and future research should focus on the identification of patients most likely to benefit from ecmo and optimization of treatment strategies after ecmo initiation [ ] . the study was supported by the direction de la recherche clinique et de l'innovation (drci), assistance publique-hopitaux de paris (aphp), with a grant from the french ministry of health (crc , # , ). the eolia trial was supported by the direction de la recherche clinique et du développement (drcd), assistance publique-hôpitaux de paris (aphp), with a grant from the french ministry of health (programme hospitalier de recherche clinique number, phrc , ), the eolia trial group, the réseau européen en ventilation artificielle (reva) and the international ecmo network (ecmonet, https ://www.inter natio nalec monet work.org). the cesar trial was supported by the uk nhs health technology assessment, english national specialist commissioning advisory group, scottish department of health, and welsh department of health. see the supplement for the list of eolia and cesar collaborators. the online version of this article (https ://doi.org/ . /s - - - ) contains supplementary 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benefits most from treatments: daft, deluded, or deft approach the preserve mortality risk score and analysis of longterm outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome ecmo for ards: from salvage to standard of care? saying no until the moment is right: initiating ecmo in the eolia era prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: time for a randomized trial we thank mrs elizabeth allen for her help in preparing the data of the cesar trial. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - avkjc authors: li, qiang; feng, wei; quan, ying-hui title: trend and forecasting of the covid- outbreak in china date: - - journal: j infect doi: . /j.jinf. . . sha: doc_id: cord_uid: avkjc by using the public data from jan. to feb. , , we perform data-driven analysis and forecasting on the covid- epidemic in mainland china, especially hubei province. our results show that the turning points of the daily infections are predicted to be feb. and feb. , , for hubei and china other than hubei, respectively. the epidemic in china is predicted to end up after mar. , , and the number of the total infections are predicted to be . the data trends reveal that quick and active strategies taken by china to reduce human exposure have already had a good impact on the control of the epidemic. a novel coronavirus from wuhan in central china, named -ncov, has recently caused an epidemic of pneumonia in humans and posed a huge threat to global public health. , to the date / / , -ncov has led to more than , confirmed cases and deaths in china according to national health commission of the people's republic of china ( http://en.nhc.gov. cn/index.html ). cases have also been documented in a growing number of other international locations, including the united states ( https://www.cdc.gov/coronavirus/ -ncov/index.html ). as a consequence, it is urgent to develop effective measures to control this novel coronavirus on the basis of its pathogenesis. host receptor recognition is a determinant for virus infection. during the time of this letter preparation, three works have just been published to explore the receptor usage of -ncov. a work by zheng-li shi et al. has shown that angiotensin-converting enzyme (ace ), the receptor for severe acute respiratory syndrome coronavirus (sars-cov), from human, rhinolophus sinicus bat, civet, swine but not mouse mediate -ncov infection in vitro , while the detailed mechanisms are not yet determined. the other two works have reported or predicted human ace usage of -ncov in a similar way to sars-cov mainly based on the coronavirus spike (s) glycoproteins. , considering the fact that the s proteins mutate and gain capability to recognize host receptors among species, , there is still a lack of analyses on receptor usage of -ncov from the receptor perspective, which does not evolve as quickly as viruses. here, we firstly performed amino acid sequence alignment of ace from different species, including human, five non-human primates (gibbon, green monkey, macaque, orangutan and chimpanzee), two companion animals (cat and dog), six domestic animals (bovine, sheep, goat, swine, horse and chicken), three wild animals (ferret, civet and chinese horseshoe bat) and two rodents (mouse and rat). the alignment by clustal w . shows that they share a high sequence similarity except chicken (data not shown). the result suggests that -ncov of probable bat origin may not interact with chicken ace and subsequently infect them, which were not considered in the following analyses. in ace , the regions at position - , - and - are demonstrated to be involved in the interaction with sars-cov s protein, where the residues at positions , , , and are critical. therefore, we took a close comparison in these regions and residues. as shown in fig. , human and non-human primates share the identity sequences in the regions and residues, implying that ace from non-human primates may recognize -ncov and medi-ate its infection. as a result, non-human primates may be susceptible to -ncov and serve as animal models for antiviral research or intermediate hosts for cross-species transmission. in fig. , the residues of most companion, domestic and wild animals are conserved, especially for the critical ones stated above, while certain ones are variable. for example, lys , glu , asp/glu and lys are conserved, which probably form salt bridges. interestingly, the changes at positions , and are observed. these changes suggest steric hindrance and electrostatic interference for host-virus interaction. taking civet ace as an example, the change of lys to thr is likely to form a hydrogen bond instead of a salt bridge. in addition, the polar side chain of thr may influence the hydrophobic interaction of the original met . all these changes may result in a lower binding affinity. however, an additional region covering residues - has been shown to be involved in civet ace binding to sars-cov and enhance their interaction. consequently, we can't preclude the existence of other regions to compensate for the residue changes. with most residues in human ace , the ones from these compaion, domestic and wild animals may be favorable for -ncov recognition, which is in consistent with the recent work by zheng-li shi et al. in case cross-species transmission, close contact with sick or asymptomatic companion, domestic and wild animals should be cautious, such as for workers in livestock farming and travellers in the wild. in contrast, certain significant changes occur in the mouse and/or rat ace compared to the human one ( fig. ) . the asn and ser in mouse ace may not form favorable interactions with -ncov due to their electrostatic or hydrophilic characteristics. importantly, the change into his in both mouse and rat ace does not form a strong salt bridge as lys does. since the structural information for mouse and rat ace is unavailable, we carried out homology modeling using human ace (pdb code ajf) as template on online ( https://swissmodel.expasy.org ) for further analyses. in fig. a, the change into ser in mouse ace may interfere with the hydrophobic interaction of the original met . additionally, the changes into asn and his definitely affect the salt bridge formation and electrostatic potential. the change into his in rat ace is similar in the effect on receptor-virus interaction ( fig. b) . these analyses partially explain why mouse ace does not mediate -ncov infection reported by zheng-li shi et al. and assume that rodents are not likely to be the susceptible host. in conclusion, we conducted sequence and structural analyses of angiotensin-converting enzyme (ace ) from different species, which sheds some light on cross-species receptor usage of -ncov. all these analyses raise an alert on a potential interspecies transmission of -ncov and propose further surveillance in other animal populations. structural studies on human and other species ace in complex with -ncov spike protein will con- the authors declare no conflict of interest. very recently, a letter in journal of infection reported the outbreak of the novel cornonavirus from dec. in china, especially in hubei province. this novel cornonavirus may originate from the bat, is just named as the covid- by the world health organization (who). the covid- outbroke from wuhan, the capital of hubei province, has spread to other provinces of china and even other countries. strong human-to-human transmission is established. until feb. , , there have been cases of covid- infections confirmed in mainland china, including deaths. to prevent and control the spread of the epidemic, many strategies are needed. predicting the trend of the epidemic are quite important to the allocation of medical resources, the arrangement of production activities, and even the domestic economic development all over china. therefore, it is very urgent to use the latest data to establish an efficient and highly suitable epidemic analysis and prediction model according to the actual situation, and then to give reliable predictions, which could provide an important refer-ence for the government to formulate emergency macroeconomic decisions and medical resources allocation. recently, the susceptible-exposed-infectious-recovered (seir) or other similar models , are used to forecast the potential domestic and international spread of this covid- epidemic with parameters estimated from other sources.the real situation could be much more complicated and changing all the time. especially, with the implementation of the chinese government's multiple epidemic control policies, the control of nationwide epidemic has become obvious. however, the medical supplies in hubei will still affect the implementation of national policies. in this letter, we present the current situation of the epidemic, predict the ongoing trend with data driven analysis, and estimate the outbreak size of the covid- in both hubei and other areas in mainland china. the data of the epidemic are listed in table and also graphically shown in fig. , in which "china" is used to denote the mainland china, and "other" mainland china other than hubei province. the data includes the daily confirmed(suspected) infections, totally confirmed(suspected) infections, daily deaths, and total deaths from jan. , to feb. , , reported by the national health commission of the republic of china (nhc), , and health commission of hubei province (hch). jan. , , containing all the cases reported from to , is the zeroth day in this letter, and then others are implied. the total number of suspected cases reaches the peak value on the th day (feb. ), and then drops rapidly. notice that, until feb. , , almost all the cases of deaths ( / , %,) locates in hubei province, which reveals the epidemic in hubei is much more serious than that in the other areas of china. on the hand, it states the strict quarantine and limitation on population mobility have effectively prevented outbreaks in other provinces of china. scribe the data of daily infections and deaths in hubei, where x = (t + . − t t ) with t denoting the day, and t t representing the turning point; a and k are the parameters and determined by the data together with t t . the cumulative data of infections or deaths are obtained by the integration over h ( t ). for the epidemic in the other areas of china, the data of infections shows an asymmetric character, and then will be described as where x = t − t t ; the parameters b, k , and k together with t t , are then determined by fitting to the data. fig. shows the fit and trend predictions to the total infections and deaths in hubei and china other than hubei. the extracted turning point of the infections in hubei is the th day, namely, feb. , . the epidemic in hubei is predicted to end after mar. , . we estimated that the epidemic is to end up with a total of , infections in hubei, not including the clinically diagnosed cases since feb. , which may enlarge the prediction by . times. with considered data, namely, data from jan. to feb. , the average errors are bout and for the fits to describe the daily and cumulative infections in hubei, respectively, corresponding to . % and . % for the average relative errors, respectively. fig. (b) and (e) shows the estimations of the total and daily deaths in hubei. the predicted turning point is feb. , . the total deaths is estimated to be . notice the distribution of the daily deaths is delayed about ∼ days compared with the that of the daily infections. the average errors are bout and for the model to describe the daily and cumulative death numbers, respectively, corresponding to the relative errors . % and . %, respectively. the numbers of the daily and total infections in china other than hubei are showed in fig. (c) and (f), respectively. the extracted turning point is feb. , and the epidemic is expected to end on the th day, namely, on mar. , . the estimated number of cumulative infections is about , in china other table the data of epidemic caused by the covid- pneumonia in the mainland china and hubei, including (a) daily infections, (b) daily deaths, (c) total infections, (d) total deaths, (e) daily and (f) total suspected cases. china hubei a b c d e f a b c d / / / / / / / / / / / / / / / / / / / / , fig. (f)), we did not parameterize this data, and hence did not give a trend prediction. the covid- epidemic in china is predicted to end after mar. , , and cause , - , infections and about deaths. however, the data trends show that the quick and active strategies to reduce human exposure taken in china, such as limi-tation on population mobility and interpersonal contact rates, strict quarantine on migrants, have already had good impacts on control of the epidemic. now the outbreak and deaths of the covid- epidemic are mainly in hubei province. after this letter has been written, the hubei reported , confirmed infections (including , clinically diagnosed cases) on feb. , , which is almost times greater than the data of the previous day. the huge fluctuation is due to the changing of diagnostic criteria in hubei. and this clinical criteria taken in hubei is expected to play an active and important role in controlling the outbreak and death rate. the authors declare no conflict of interest. dear editor , recently, several studies in this journal have highlighted the threat of avian influenza virus (aiv) to humans, poultry, and other animals. [ ] [ ] [ ] [ ] [ ] [ ] in equines, there was only one reported influenza outbreak caused by aiv, which occurred in - in china. however, aiv still poses a potential threat to equines. in contrast to aiv, equine influenza virus (eiv) is a commonly known causative pathogen of acute respiratory disease in equines. to date, two subtypes of eivs have been determined in the equine population worldwide: h n and h n . h n eiv was initially identified in prague in , and the last outbreak caused by h n eiv occurred in . h n eiv was first isolated in miami in and is currently responsible for ei outbreaks worldwide. during continuous transmission and evolution in equines, h n eiv strains diverged genetically into three distinct lineages: predivergent, european, and american. historically, there have been four main ei outbreaks in mainland china, occurring in china, occurring in , china, occurring in - china, occurring in , , and - . in the first, third, and fourth outbreaks, the isolated eiv strains were of the h n subtype, h n subtype european lineage, and h n subtype american lineage, respectively. in the second ei outbreak, the causative pathogen (a/equine/jilin/ / ) was determined to be h n subtype influenza a virus (iav) by antigenicity characterization. however, after genetic sequencing, all eight segments of a/equine/jilin/ / were genetically closer to those of avian influenza virus than those of eiv, indicating an interspecies transmission event. the - ei outbreaks in china contain two major outbreaks. the first ei outbreak occurred in jilin and heilongjiang provinces between march and june , with a morbidity of % and a mortality of up to % in some herds. the second ei outbreak occurred in heilongjiang province in april , with a morbidity of % and no mortality. the high mortality and unique antigenicity of a/equine/jilin/ / attracted the attention of eiv researchers. however, after the - ei outbreaks in china, the virus disappeared from the equine population for unknown reasons. although no evidence in the epidemiological investigation worldwide supports the continuous circulation of a/equine/jilin/ / -like eiv in equines, we should not underestimate the potential of interspecies aiv transmission to equines and the possibility of future ei outbreaks caused by aiv. the haemagglutinin (ha) of iavs recognizes and binds the cell surface sialic acid (sa) receptor of the host respiratory tract, and then the virus enters into cells and replicates. the distribution of the sa receptor influences the host range of iavs. human influenza viruses preferentially bind the saa , gal receptor, while aivs preferentially bind the saa , gal receptor. it has been reported that the saa , gal receptor is abundant in the epithelial cells of the horse trachea, and animal experiments indicate that iavs with an ha recognizing the saa , gal receptor could replicate in horses. this finding provides a prerequisite for cross-species transmission of aiv to equines. in fact, there were several pieces of direct molecular evidence supporting the interspecies transmission of aiv to equines, in addition to the - ei outbreaks in china. in , abdel-moneim et al. reported one h n eiv strain (a/equine/egypt/ av / ) isolated from donkeys with cough, fever and serous nasal discharge in egypt. sequencing results indicated that the virus had a close genetic relatedness to h n aiv. in addition, h seroconversion was observed in . % ( / ) of the examined donkeys. in , he collected equine lung tissue samples in china and isolated one aiv-derived h n eiv strain (a/equine/guangxi/ / ) ( https://kns.cnki.net/ kcms/detail/detail.aspx?dbcode=cmfd&dbname=cmfd & filename= .nh&v=mtmxmzc ck wrji sexleedove x wkviuelsogvymux efltn romvqzcvryv xrnjdvvjmt vazvpt rknua u= ). among the tested equine serum samples in china, . % ( / ) of samples were positive for anti-h n antibody. in the - ei outbreaks in pakistan, khana et al. reported that the isolated eiv strain (a/equine/pakistan/ ) was reassorted from aiv. the common characteristic for the reported cross-species transmission events of aiv to equines in china, pakistan, and egypt is that they occur in farming equines. , in the mixed farming system, equines and domestic poultry often live in close proximity. compared with racehorses, farming equines have more opportunities to contact domestic poultry and experience long-term environmental exposure to poultry. aiv infections in poultry increase exposure risks to equines. recently, frequent reports of cross-species transmission events of aiv to farming dogs in china and korea also indicate the potential threat of aiv to farming animals with close contact with poultry. another problem is that the farming equines in china, pakistan, and egypt had no vaccination history. even in some racehorse populations, vaccinations for eiv are not routinely performed as recommended by the world organization for animal health (oie) expert surveillance panel on ei vaccine composition. although h n eiv is antigenically distinct from a/equine/jilin/ / , animal experiments indicated that high doses of ei vaccines still provided complete protection against challenge with a/equine/jilin/ / . accordingly, routine vaccination with h n ei vaccines in equines might prevent aiv infection to some degree, at least for h n subtype aiv. several strategies may help reduce the threat of aiv to equines, including reducing exposure of equines to poultry, birds, and other hosts of iav, especially animals with clinical signs of influenza virus infection; monitoring aiv prevalence in domestic poultry around equines and routinely vaccinating domestic poultry with aiv vaccines; vaccinating susceptible equines with ei vaccines, especially farming equines in close contact with domestic poultry; and monitoring the prevalence of multiple aiv subtypes in equines, not merely that of those restricted to h n subtype. none. we read with interest recent articles in this journal regarding the utility of next-generation sequencing for the diagnosis bacterial meningitis. , bacterial meningitis causes substantial morbidity and mortality worldwide. rapid identification of the microorganisms is essential for early initiation of appropriate antimicrobial therapy, thereby improving clinical outcome. yet routine diagnostic methods fail to identify the bacteria in the majority of patients. over the last decade, advanced sequencing technologies have greatly improved our capacity to detect the causative agents of infectious diseases in clinical samples. , of these, the single molecule real-time sequencing developed by oxford nanopore technologies (ont) is a promising tool for diagnostic setting because of its short turnaround time. in late april , a -year old seller of fish-noodles was referred to our hospital with a -day history of headache, fever and vomiting. he had a history of heavy alcohol use and hepatitis c infection, and had cirrhosis and diabetes mellitus. on admission, he was unconsciousness (a glasgow coma scale of ), with a body temperature of °c, a blood pressure of / mmhg and neck stiffness. initial gram-stain and microscopy of csf showed grampositive cocci, white cells/ul with % neutrophils, elevated protein and low glucose level, and high lactate concentration ( fig. a) . routine bacterial culture, plus streptococcus pneumoniae and s. suis pcrs were all negative. he was diagnosed with bacterial meningitis, and given a combination of ceftriaxone ( g/ h) and dexamethasone ( . mg/kg/ h). his clinical condition steadily improved. his second and third csf samples became negative by gram stain. the other csf parameters also improved, except the glucose, which remained low ( fig. a) . on day of hospitalization, the patient suddenly became unconsciousness with fever. brain magnetic resonance imaging showed bifrontal abscesses ( fig. b) . after consulting a local neurosurgeon, aspiration of the brain abscesses was not advised and the patient was treated empirically with meropenem ( g/ h) and vancomycin ( g/ h). due to continued diagnostic uncertainty, we performed s rrna sequencing of the admission csf, stored as part of an going clinical study (supplementary materials), using an established sangersequencing based s rrna method. subsequently, analysis of the obtained sequences revealed evidence of s. agalactiae (supplementary figure ). given this new diagnostic result of the admission csf and because the patient had recovered clinically, the patient was given million units of penicillin g for every h. after day of hospitalization, all csf parameters had normalised ( fig. a) . likewise, on ct scan the brain abscess was now significantly improved ( fig. c) . the patient was discharged with full clinical recovery. additionally, minion sequencing of complete s rrna gene was retrospectively carried out on the extracted nucleic acid of the admission csf yielded a total of , reads after min of sequencing run. of these, , reads ( %) were successfully aligned to s. agalactiae ( fig. d) . the remaining reads were assigned to other streptococcus species (mostly s. dysgalacticiae ( n = . , %)), likely attributed to a combination of the high level of sequence similarities of the s rrna region between them and the sequencing errors introduced by the minion systems. analysis of sequencing data generated during the , and min of sequencing run time also yielded the same results (supplementary figure ). details about the minion procedure are presented in supplementary materials. to further assess of the utility of csf minion sequencing of s rrna gene for the detection of bacterial meningitis pathogens, six csf samples from patients with confirmed bacterial meningitis enrolled in the abovementioned clinical study were tested ( table ) . analysis of the minion reads obtained after two hours of the sequencing run showed that the majority of reads were correctly assigned to the corresponding bacterial species ( s. pneumoniae and s. suis) or genus ( neisseria ) found in the csf samples by diagnostic work up of the clinical study ( fig. e and table ). additional analysis of the obtained reads generated at two earlier time points ( min and min) of the sequencing run generated the same results ( table ) . collectively, we report the first application of minion sequencing of s rrna gene to detect bacterial meningitis causing pathogens in csf samples from a low and middle-income country. the assay was able to detect the bacterial causes in all of the seven tested csf samples. meanwhile, gram stain and culture, the two most commonly used methods in clinical microbiology laboratories worldwide, were negative in / samples. ( fig. and table ). in addition to csf samples described in the present study and a recent pilot study from korea, successful detections of haemophilus influenzae in sputum and campylobacter fetus in culture materials by minion sequencing of s rrna have recently been reported. together, the data suggest that minion sequencing of s rrna is a sensitive method for rapid and accurate detection of pan-bacterial pathogens, including unexpected microorganisms, in clinical samples. additionally, the bacterial species information generated by the analysis of s rrna sequences can be useful for disease surveillance and vaccine evaluation. thus, the application of the method would be relevant for both patient management and epidemiological research. indeed, to the best of our knowledge the present study represents the first report of s. agalactiae associated meningitis in vietnam. because the incidence of invasive diseases (including meningitis) caused by s. agalactiae has been reported with increased frequency in recent years, s. agalactiae should be considered as an important differential owing to the unavailability of the reagents at the time of patient admission, we were not able to perform real-time diagnosis using minion sequencing on the collected csf samples. however, same day diagnosis is theoretically achievable, because the current workflow takes - h to operate. prospective study is urgently needed to assess its translational potential in the diagnosis of bacterial meningitis. since september , a prospective observational study aiming at exploring the utility potential of next-generation sequencing in patients presenting with central nervous system (cns) infections has been conducted in the brain infection ward of the hospital for tropical diseases (htd) in ho chi minh city, vietnam. htd is a tertiary referral hospital for patients with infectious diseases from southern provinces of vietnam, serving a population of > million. any patient ( ≥ years) with an indication for lumbar puncture was eligible for enrolment. patient was excluded if no written informed consent was obtained. as per the study protocol, csf, plasma and urine samples were collected at presentation alongside demographic, meta-clinical data and results of routine diagnosis. after collection, all clinical specimens were stored at − °c until analysis. the clinical study received approvals from the institutional review board of the htd and the oxford tropical research ethics committee of the university of oxford. written informed consent was obtained from each study participant or relative (if the patient was unconsciousness). sequencing of complete s rrna gene was retrospectively performed using minion nanopore sequencer (ont), following the manufacturer's instructions. in brief, amplification of the complete s rrna gene and library preparation were carried out on extracted nucleic acid using s barcoding kit (sqk-rab , ont) and primers ( f -agagtttgatcctggctcag- and r -ggttaccttgttacgactt- ), followed by the sequencing of the amplified product using r . flow cells (ont). minion reads were first basecalled using albacore v . . (ont), followed by demultiplexing using porechop ( https://github.com/rrwick/porechop ). determination of bacterial genus/species composition in the obtained reads was then carried out using epi me interface (metrichor, oxford, uk), a platform for cloud-based analysis of minion data. overall, the whole procedure of minion sequencing of s rrna gene takes - h to complete (supplementary figure ) . we, the author of the submitted manuscript declare that we do not have a commercial or other association that might pose a conflict of interest (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding). dear editor, several aspects of influenza have been highlighted recently, including its global, comparative seasonality, and issues around rapid point-of-care testing. in addition, the uk has a national surveillance programme, the uk severe influenza surveillance system (usiss) to monitor and investigate severe cases of influenza across the country, including severe cases of influenza admitted to intensive care (icu) and high dependency units (hdu). specifically, the aim of this latter arm was to "monitor and estimate the impact of seasonal influenza on the population" and to "describe the epidemiology of severe disease." this surveillance began in the - influenza season and has continued to the present, with mandatory participation by all nhs trusts. leicester is one of nhs commissioned centres in the uk providing extra-corporeal membrane oxygenation (ecmo) support for severe acute respiratory failure in adults. this process involves draining deoxygenated venous blood from the superior and inferior vena cavae, pumping this blood through a membrane lung, where oxygenation and carbon dioxide elimination take place. oxygenated blood is delivered back into the right atrium, therefore replacing the function of the native lung. in this way, ecmo can be used to support patients with respiratory failure of any cause. acceptance for admission for ecmo support follows referral to the ecmo service via structured questionnaire and discussion with the ecmo consultant on-call. patients are commenced on ecmo where benefits are deemed to outweigh the risks in patients with potentially reversible respiratory failure, who are already on maximal conventional therapy at their referring centre, and who are not achieving lung protective ventilation. here, as part of our national usiss role, we describe severe influenza cases that required ecmo support in whom the predominant indications were severe hypoxia with a pao :fio ratio of < despite maximal conventional therapy, and/or hypercapnoeic respiratory failure with a ph < . despite ventilation pressures > cm h o. during the - influenza season cases of severe influenza were admitted to glenfield hospital for ecmo from our referring centres. most were male ( / , . %, - years, bmi: - ; female / , - years, bmi: - ), and of white british ethnicity ( / , . %; with each of chinese, asian, african ethnicity). comorbidities included, obesity, hypertension, asthma, copd, diabetes, anxiety, depression, epilepsy, a history of smoking and alcohol use (or abuse). all cases except for one influenza a(h n ) infection (possibly two as subtyping was not performed for another sample) were due to influenza a(h n )pdm . only one case had a history of influenza vaccination. various 'on referral' ecmo-related parameters were extracted, as well as contemporaneous laboratory results. these were statistically compared between patients who died ( n = ) and those who survived using t -test or mann-whitney test for continuous variables and fisherexact test for categorical variables. correlation between duration on ecmo and laboratory parameters was assessed using spearman's rank correlation coefficient. ( n = ) ( tables and ) . surprisingly, it was found that on direct comparison, most of the referral parameters for patients starting ecmo were not statistically different between those influenza-infected patients that eventually survived ( n = ) versus those who died ( n = ) -a case fatality rate of %. one patient was dropped from this analysis due to some missing data. only the respiratory rate (rr, p = . ) and the lactate ( p = . ) showed statistically significant differences between the two groups, with higher values being found in the patients who ecmo -extra-corporeal membrane oxygenation; sofa -sequential organ failure assessment; peep -positive end expiratory pressure; h o -water; bpm -breaths per minute; pao /paco -partial pressure of arterial oxygen/carbon dioxide; altalanine aminotransferase. * rank correlation coefficient measures the strength and direction of a relationship between two variables. the coefficient ranges from − to with indicating a strong positive relationship between two variables and − indicating a strong negative relationship. a correlation coefficient close to means the relationship between the two variables is very weak. died ( table ) . however, clinically, these differences are of doubtful significance, as the rr is at the discretion of the parent clinical team prior to referral to ecmo, and the lactate levels are normal in the survivors and only marginally elevated in those who died which will again be dependent on use of cvvh. the higher pao :fio (p:f) ratio was statistically significantly correlated ( p = . ) with a shorter duration of ecmo, which suggests those with less severe disease recover quicker ( table ) . many studies have reported on intensive care patient outcomes of the influenza a(h n )pdm pandemic, with or without the use of ecmo. in one study from australia, where ecmo was used, of patients with confirmed influenza a ( a(h n )pdm , un-subtyped) infection, ( %) had died mainly due to intracranial and other forms of haemorrhage ( n = ), or intractable respiratory failure ( n = ). another study from the usa, where influenza a(h n )pdm -infected patients had non-ecmo icu admission, of cases, ( %) developed acute respiratory distress syndrome (ards), of whom ( %) died. a more recent study from spain that reviewed influenza a(h n )pdm cases admitted to icu (non-ecmo) from - , found that of a total of cases, the mortality ranged from . % (for community-acquired influenza) to . % (for hospitalacquired influenza). these ecmo-icu case fatality rates of severe influenza a(h n )pdm infection are similar to ours of % reported here, though compared to the specific ecmo patient cohort, the causes of death in our patients were more variable, including intracranial and other haemorrhage ( n = ), sepsis and multi-organ failure ( n = ), respiratory failure ( n = ), post-cardiopulmonary resuscitation hypoxic brain injury ( n = ), and ischaemic bowel associated with atrial fibrillation ( n = ). thus, even after years of experience with this 'new' pandemic influenza a(h n )pdm virus, across almost the entire adult age-range ( ∼ - years in these previous studies), - it appears that for severe cases, globally, the survival of such patients appears not to have improved. this may be somewhat surprising as the world's populations have become more immunologically experienced with this virus, which is now considered as a seasonal influenza virus that should be conferring some degree of persisting, cross-reactive individual and herd immunity over consecutive seasons. this may be due to some predisposing genetic or environmental factors in individual patients, which should reinforce the general message that seasonal influenza immunisation is still recommended to minimise the number of people needing icu or ecmo support for severe influenza infection. more detailed monitoring on how these physiological parameters change over time (perhaps including more complex cytokine studies), in these severely ill, influenza a(h n )pdm -infected patients admitted to icu-ecmo units, may eventually yield data to improve their management and clinical outcomes. none. we read with interest the report by stalenhoef and colleagues in this journal who show that biomarker guided triage can reduce hospitalization rate in community acquired febrile urinary tract infection (ref). here we report on a prospective observational analysis of the biomarker: cd antigen like protein (cd l), in serum samples collected from patients diagnosed with pneumonia and healthy adults between and . the demographic and clinical characteristics of the adults (males . %; mean age ± years) with pneumonia were summarized in table . ( . %) bacterial pneumonia patients (including patients with confirmed bacterial pneumonia and patients with suspected bacterial pneumonia ) and ( . %) viral pneumonia patients were studied. there were significant differences in age, sex, wbc, neu%, crp, pct, cd l, apache ii scores and length of icu stay between bacterial pneumonia and viral pneumonia. the pathogens responsible for pneumonia were described in supplementary table . globally, gram-negative bacteria infection is more common than gram-positive bacteria infection in pneumonia. among them, acinetobacter baumannii ( , . %) was considered the major pathogen in gram-negative bacteria and staphylococcus aureus ( , . %) was considered the major pathogen in gram-positive bacteria. in viral pneumonia, influenza a (h n ) was detected as the unique pathogen. in the study of the diagnostic performance of serum cd l to identify etiology of pneumonia, as we found in supplementary fig. , no matter in total bacterial pneumonia, suspected bacterial pneumonia or confirmed bacterial pneumonia, the serum of cd l levels on day of pneumonia diagnosis were significantly higher than those in viral pneumonia and healthy control subjects. for evaluating the diagnostic performance of cd l to differentiate bacterial from viral infection in pneumonia, roc analysis was conducted for the above bacterial pneumonia (supplementary fig. ) and compared with routine laboratory markers ( table ). by horizontal comparison, we found that the best auc was for cd l (auc = . ), better than neu% (auc = . ), wbc (auc = . ), crp (auc = . ) and even pct (auc = . ). interestingly, by longitudinal comparison, the auc was observed highest in confirmed bacterial pneumonia (auc = . ), intermediate in all bacterial pneumonia (auc = . ), and lowest in suspected bacterial pneumonia (auc = . ), which may better elucidate the diagnostic performance of cd l for etiology diagnosis in pneumonia patients. although there are patients with suspected bacterial pneumonia for which no definitive pathogen was found, our result here may still provide a new treatment for bacterial infection identification in pneumonia patients for the current limitations in direct pathogen testing make it difficult to identify the pathogen at the time of diagnosis . besides, as a potential biomarker to distinguish pathogens - , cd l levels were also significantly correlated with wbc, neu%, crp and pct ( supplementary fig. ) in patients with pneumonia. in the study of the diagnostic performance of serum cd l to predict mortality in adults with pneumonia, mortality was defined as death occurring within days after the onset of pneumonia. as we observed in supplementary fig. a , serum cd l levels on day of pneumonia diagnosis were significantly higher in non-survivors ( n = ) than survivors ( n = ) ( p < . ). to ensure that serum cd l levels were not influenced by the class of the infection in the specimens, spearman's rank correlation analysis was performed between serum cd l levels and poor prognosis related scores , (sofa and apache ii scores) in patients with total bacterial pneumonia, suspected bacterial pneumonia, confirmed bacterial pneumonia and viral pneumonia, respectively. our correlation analysis between serum cd l levels and sofa or apache ii scores shows that no matter for bacterial pneumonia or viral pneumonia, the cd l levels showed positive correlation with sofa and apache ii scores ( supplementary figs. and ) . furthermore, the auc of cd l for identifying -day mortality in adult pneumonia patients was . ( supplementary fig. b) , a value means good diagnostic performance, which is consistent with gao's study before. therefore, we found that determining serum cd l concentrations on day of pneumonia diagnosis was of great value in identifying bacterial infection from viral infection and predicting day mortality in adult patients with pneumonia, which suggests that cd l may work for the etiologic diagnosis and could represent a novel biomarker for identification of a group of patients with pneumonia presenting with higher risk of death. these findings encourage further effort s aimed at exploring the clinical value of circulating cd l to help early clinical decision-making in human pneumonia. none. high morbidity and mortality (up to %). asf is a devastating threat to pig agriculture and is responsible for serious production and economic losses. the asfv genome is - kilo base pairs in length and has been divided into different genotypes based on their b l gene sequence, a gene which encodes the capsid protein p . , our previous study showed that the p gene located in a very low genetic diversity region of the genome. ye and colleagues, however, identified two novel genotypes xxv and xxvi, with genotype xxvi being especially divergent from all other genotypes. to examine this unexpected result, in this study, we reanalyzed their data to evaluate the reliability of these two genotypes. we collected available p gene sequences from ncbi ( http://www.ncbi.nlm.nih.gov/ ), which we then aligned with mafft software, a fast multiple sequence alignment program. the alignments show that genotype xxv (accession number fr ) has a single amino acid change at position compared to genotype i, while for genotype xxvi (accession numbers fr and fr ), the region coding for amino acid residues to differs greatly compared to all other genotypes ( fig. a) . to examine this in greater detail, we calculated genetic distance across the p coding sequence in bp sliding windows, with a step size of bp, between these two sequences and the other genotypes ( fig. b) . this sliding window analysis shows these two sequences for genotype xxvi have a region that is very divergent, with genetic distance up to . from the other genotypes, while the genetic distances of the remaining regions are less than . ( fig. b) . genetic distances for asfvs were calculated for coding gene sequences, from available complete genomes of asfvs, to assess the overall divergence. pairwise genetic distances of each gene for all asfv strains were calculated. the mean pairwise genetic distance for asfv genes was . ( fig. ) , which is much lower than this divergent region of these two sequences for genotype xxvi ( . ). therefore, it seems highly unlikely that a gene has such a highly divergent region. since recombination frequently occurs in asfvs, we conducted a recombination analysis with the rdp program, which used the seq, bootscan, chimaera, genecov, lard, maxchi, rdp and siscan detection methods, to determine whether recombination might have occurred in the xxvi genotype. we found reliable evidence for recombination events in both p genotype xxvi sequences ( fig. c) . this suggests that the very highly divergent region of this p genotype is not homologous with other p genotypes. we used blastn, from ncbi ( https://blast.ncbi.nlm.nih.gov/blast.cgi ), to identify a source for this highly divergent region, however, no similarity sequence was found. we then mapped the multiple amino acid changes found in genotype xxvi to the d structure of p ( fig. ) . the changed sites (marked in red in fig. ) are located in the dec loop, a region which plays an important role in the formation of the trimer spike. the amino acid mutations result in changes of electrostatic potential, hydrophobicity, and steric hindrance. it seems unlikely to have so many changes in such a functionally important region. in our previous studies we noticed that sequences directly submitted by individual laboratories to genbank often contain errors such as misidentification of species, sampling error, contamination, or are pseudogenes, which can lead to sequence analysis problems and erroneous conclusions. , sequences that deviate from the overall intraspecific pairwise divergence are potentially erroneous. , since genotype xxvi deviates from other genotypes not only in genetic distance, but also in protein structure, and mutations occur in the flanking regions of the sequences, we deduced that these reported mutations might be due to low quality sequencing. we identified the original manuscript reporting the three sequences of genotypes xxv and xxvi, where the authors stated that the "alignment and translation of sequences obtained from sardinian isolates revealed that the c-terminal end of p gene was completely conserved between the sequences compared". this statement indicates that these sequences did not considerably diverge from previously reported asfv p sequences, and thus, suggests that an error in these sequences had been introduced upon submitting them to genbank. further examination of the original samples and sequences is needed. we contacted the corresponding author of this manuscript to check these three sequences, and were told that these three p sequences were all genotype i, and had some errors when submitted to genbank. in conclusion, the two novel genotypes of asfvs (xxv and xxvi) identified by ye and colleagues are misled by problematic sequences. as reminded by our previous studies, many problematic sequences are present in genbank, which can lead to problems in downstream analyses. , thus, when published data is used for new analyses, the first set in the process of data analyses should be to filter these sequences for potential errors to reduce the possibility of reaching incorrect conclusions. if conclusions are based on obviously strange sequences, then we should trace back the data to their original source, and manuscript, and contact the corresponding authors before making conclusions based on these sequences. the authors declare no conflict of interest. fig. . the analyses of phylogenetic tree, recombinant, and nucleotide divergence between xi and the other known subtypes ( a- xh) based on full-length hbv genome sequences. (a) the known hcv subtype reference sequences ( a- xh) from the previous report were used. phylogenetic analysis was performed by the maximum-likelihood method, based on the gtr + g + i substitution model, with bootstrap replicates using the software mega v . the sequences of hcv xi (ynkh and ynkh ) are marked in red dot. (b) bootscan plots were constructed using simplot . . software based on replicates with a -bp sliding window moving in steps of bases. (c) pairwise comparisons of nucleotides similarities between hcv xi strains and reference genotype sequences. , deaths per year. currently, daa treatment regimens that target ns /ns a protease, ns a phosphor-protein and the ns b polymerase have shown high safe and high rates of sustained virologic response in hcv chronically infected patients ( > %). however, under selective pressure from these drugs, drug resistance-associated substitutions (ras) can emerge during this therapy and result in treatment failure in − % of patients. therefore, hcv infection is still a major global health concern. to date, eight confirmed genotypes have been characterized based on > % sequence divergence in the complete hcv genome, and genotypes are further classified into > subtypes with a sequence divergence of > % to other subtypes of the same geno-type. in the current study, we characterized a new hcv subtypes among chronic hepatitis c patients in yunnan, china, initially designated as xi, further analyzed its evolutionary history and investigated its baseline ras by next generation sequencing (ngs) method. plasma samples were collected between january and october from chronic hepatitis c patients from kunming city in yunnan, china (fig. s a) . the samples met the following inclusion criteria: ( ) hepatitis c antibody-positive for months with normal serum alanine aminotransferase (alt) levels; ( ) subject was residing in yunnan province and was over years old; ( ) complete demographic information and clinical data were available; ( ) consented to the use of patient information in studies on hcv epidemics; and ( ) were treatment-naïve during sampling. there was no epidemiologic link among these individuals. the study was approved by the first people's hospital of yunnan province ethics committee. written informed consent was obtained from all participants prior to the study. out of a total of chronic hepatitis c patients, partial ns b gene fragments were successfully amplified and sequenced with a success rate of . % ( / ). multiple subtypes were identified in subjects, including subtype b ( . %, / ), a ( . %, / ), b ( . %, / ), a ( . %, / ), n ( . %, / ), a ( . %, / ), and a ( . %, / ) (fig. s b) . interestingly, the remaining two strains ( . %, / ) involving ynkh and ynkh together with the isolate km reported formed a novel separate cluster in the genotype with an % bootstrap value, indicating a potential new hcv subtype . to confirm that the two strains belong to a novel hcv subtype , their complete genome sequences were successfully amplified and sequenced with overlapping fragments. further, phylogenetic analysis was performed along with hcv reference sequences of representative subtypes a- xh. the result showed that the two strains and isolate km formed a distinct monophyletic cluster supported by a high bootstrap value of %. the three strains were isolated from three hiv- infected patients without obvious epidemiological linkage in yunnan and showed no evidence of recombination using bootscan analysis ( fig. (b) ). moreover, the intergroup nucleotide divergence (mean ± sd) % over the fulllength genome sequences of the isolates (ynkh , ynkh , and km ) were compared to that of representative subtypes ( a- xh) ( fig. (c) ). the results revealed that the three strains were different from known hcv subtypes of a- xh by . - . %. therefore, the three strains are initially designated xi. to better understand the time of emergence of hcv xi, we performed bayesian molecular clock analyses using full-length genome sequences to estimate the time to the most recent common ancestor (tmrca). as shown in fig. (a) , the estimated tmr-cas for the genotype xi was . [ % highest probability density (hpd): . , . ]. in addition, to further investigate baseline ras of subtype xi, naturally occurring resistance-associated substitutions (ras) were analyzed for the ns , ns a and ns b sequences using next generation sequencing (ngs) method. strikingly, hcv xi strains contain the substitution v with a % frequency of mutations in the ns a protein contributing to resistance to velpatasvir of ns a phosphoprotein inhibitor, suggesting that the subtype xi maybe basically resistant to ns a inhibitors ( fig. (b) ). among the hcv eight genotypes, genotype exhibits a high degree of genetic complexity and diversity, and subtypes have been confirmed by the international committee on taxonomy of viruses. in china, hcv genotype is common, and subtype a is the most prevalent subtype, primarily distributed in guangdong, n is the second most prevalent subtype, mainly found in yunnan, followed by subtypes xa, g, v, w, e, b, j, q,and r among genotype isolates. - to our knowledge, xi is the eighth detection of novel hcv subtypes in china combined with previously identified a, e, n, v, xa, xe and xh, resulting in genotype to expand to subtypes in the world. our findings again demonstrated that hcv genotype was more complex and diverse. in summary, we characterized a new hcv subtype xi based on the characteristics of a monophyletic cluster, > % genetic distances, no significant evidence of recombination, and no epidemiologic link among individuals. in addition, bayesian analyses showed that xi may originate around the year , and the strains of hcv xi naturally contain the substitution v in the ns a protein contributing to resistance to velpatasvir of ns a phosphoprotein inhibitor. the present finding again highlights the genetic characteristics and hcv strains in yunnan, and the urgent need for continuous molecular screening and epidemic surveillance in yunnan to implement effective measures to reduce hcv transmission. the authors declare no competing financial interests. we recently read the article by corma-gómez a. et al. on which the authors described a higher probability of relapses with sofosbuvir/ledipasvir weeks compared with weeks of hcv (hepatitis c virus) among hiv (human immunodeficiency virus)/hcv coinfected patients. in this regard, coinfections of hiv/ hcv also with hepatitis b virus (hbv) is associated with high mortality and comorbidity too. the persistence of hbv dna within the core cell in the absence of hbsag and even after clearance of the infection has been described previously in immunosuppressed patients, where hbv screening and prophylaxis is recommended. interestingly, hbv reactivation has recently emerged during or after hcv treatment with direct-acting antivirals (daa). [ ] [ ] [ ] the us food and drug administration issued a warning about this risk in , until that moment cases were reported, two of which died. although specific mechanisms of this event are not well known, it has been suggested that hcv core proteins could inhibit hbv replication and hbsag production as well as production of envelope proteins, being hbcab the only marker of the presence of hbv. in this context, treatment with daa would produce a drastic and rapidly blocking of hcv replication providing the opportunity to hbv to emerge and produce an immune reconstitution syndrome. the interference hbv-hcv has been outlined in % of patients with chronic hbv infection (hbsag-positive serology) and . % of patients with resolved hbv infections (hbsag-negative and hbcabpositive) in a recently published systematic review and metaanalysis of patients with hcv-hbv. in most cases, these reports have focused on coinfection hcv-hbv, but there is still a concern about patients triple-infected with hcv, hbv and hiv. although most cases reported occur in hbsag-positive, the main concern affects to patients with a basal serology showing hbcab-positive, hbsag-negative and hbsab-negative. hbsagpositive was associated with higher rates of hbv reactivations compared with hbsag-negative and hbcab-positive patients. there is no clear information about this issue in hbsag-negative, hbcab-positive, and, when occurs, it is considered an uncommon event. reactivation of hbv is characterized by reappearance or increase in hbv dna levels, and could also be accompanied by symptoms of hepatitis. the cases reported previously did show difference in the time of presentation of clinical symptoms, they used to start either during or after daa treatment. it seems that hbv reactivation usually occurs early after daa initiation treatment ( - weeks) while otherwise can occur after treatment completion. in that way, it seems necessary that hbv infection should be monitored early after daa initiation. the most recent european association for the study of the liver (easl) guideline about hbv infection, recommends that patients hbsag-negative and hbcab-positive undergoing daa treatment should be monitored and tested for hbv reactivation only in case of alt elevation. they also recommend performing hbv dna levels only in case of alt increase. at the same time, the american association for the study of liver diseases (aasld) and the infectious disease society of america (idsa) guideline has been recently updated recommendations to monitor hbv dna levels only in patients hbsag-positive, but they emphasize that there is not enough data to monitoring dna among patients hbcabpositive or hbcab-positive and hbsab-positive. they remark that a reactivation should be considered if an unexplained increase in liver enzyme is present. in hiv patients, they provide the same recommendations. in a recent review of the literature, the authors also recommend to perform an hbv dna only in patients with altered alt. a meta-analysis recommended not to perform an hbv dna test in this case due to low rate of incidence and the associated cost which needs to be considered especially in an endemic hbv areas. few data exist in hiv patients. the fact that many triple-infected patients are receiving antiretroviral therapy including (art) nucleoside/nucleotide analogous, as tenofovir disoproxil fumarate (tdf) or tenofovir alafenamide (taf), both active against hbv, suggest that hbv reactivation rate could be underestimated. in a recently published review, chang et al., recommend to perform an hbv dna test at baseline in triple-infected patients. if positive, an hbv-active antiretroviral therapy (art) should be started and hbv dna needs to be monitored every weeks during treatment and until week after completion of treatment. however, if baseline hbv dna is negative they match with aasld/idsa and easl recommendations. one of our patients has a basal serology with hbcab-iggpositive, both hbsag-and hbsab-negatives, and undetectable hbv dna levels, prior to treatment with daas. regarding hiv infection, he has an analogues-free regimen. one month after having finished treatment with daas, the patient consulted because of abdominal pain, nausea and jaundice. he had a total bilirubin level of mg/dl, ast iu/l, alt iu/l and inr . . a hbv viral load of , , iu/ml was detected; hbsag, hbcab-igm and hbeag were positive. there were no reasons to believe that he was re-infected. treatment with entecavir was initiated; however, the clinical evolution was unfavorable and died as a result of an acute liver failure. the hbv viral load was requested from the stored samples drawn during the treatment of hcv showing that hbv viral load was undetectable at the beginning of treatment and in week , but progressively increased to iu/ml in week and up to , iu/ml in week after treatment completion. during the follow-up of daa treatment alt and ast remained normal. this case changed our daily practice, since then all hiv patients and more specifically those not treated with either tdf or taf and presenting a previous hbcab-positive, are followed using dna levels and not only monitoring hepatic enzymes, as recommended by guidelines. we consider that this case may reflect the necessity of change the current guidelines. we recommend to perform a periodic monitoring of hbv reactivation using hbv dna during and after daa therapy in hbsag-negative and hbcab-positive patients, independently of hbsab presence, hepatic enzymes and clinical symptoms, particularly in hiv patients who are not receiving active treatment of hbv. the study was not funded. authors declare that there is no conflict of interest. recently, a notable pattern of synchrony of influenza a and b virus, and respiratory syncytial virus incidence peaks globally was reported in this journal. a previous study characterized seasonal pattern of influenza a and b in china and identified three epidemiological regions featured by distinct seasonality. on the basis of laboratory surveillance data from chinese provinces spanning about years from october through january , our study further characterized seasonal patterns of circulating influenza a subtypes and influenza b lineages in the three defined epidemiological regions. our study revealed that pre- a(h n ) and a(h n ) displayed wintertime and summertime epidemics in midlatitude and southernmost chinese provinces with subtropical climate, wavelet analysis demonstrated the two subtypes displayed twice-annual cycle in some years in mid-latitude chinese provinces ( fig. (a)-(h) ). however, the two subtypes peaks in the winter with annual or longer cycle in northern chinese provinces. influenza a(h n )pdm b/victoria and b/yamagata virus all displayed epidemics in the winter or winter-spring with annual or longer cycle in all three epidemiological regions. we developed univariate and multivariate regression models to evaluate the association between climatic factors and the presence or absence of epidemics of each influenza subtype and lineage (positive proportion ≥ %) in the southernmost provinces where heating system is not generally used in the winter so temperature and relative humidity in external conditions in winter are close to those in indoor environment where people spend most of the time. we fitted the mixed-effects logistic regression model to control for the repeated measurements in each province of the region cluster. we kept one of temperature and absolute humidity (representative of vapor pressure) with smaller akaike information criterion in the model to reduce of multi-collinearity due to a high degree of correlation between the two factors. our analysis indicated temperature, humidity and rainfall were environmental predictors of influenza subtype/lineage-specific epidemics in the southernmost provinces when a -week lag of influenza epidemics behind climate was considered, which was similar to the findings from some ecological studies ( table ). our study indicated the u-shaped relationship between absolute humidity (ah) and pre- a(h n ) or a(h n ) epidemics in the southernmost provinces, and suggest that high levels of ah in the summer, and low levels of ah in the winter increased the possibility of epidemics of the two subtypes. in our analysis, lower temperature was an environmental driver of a (h n )pdm and b/yamagata epidemics in the southernmost provinces while there were bimodal associations between temperature, rainfall and b/victoria epidemics with highest probability of b/victoria epidemics at . °c of daily average temperature and . mm of daily average rainfall. although seasonal changes in human behaviors, such as school attendance or crowding indoors, and seasonal variations in immunity, such as melatonin and vitamin d levels have been proposed to account for the seasonal nature of influenza, our findings suggest that the heterogeneity in influenza subtype/lineage-specific seasonality patterns could be driven by seasonal variations in virus survival, transmission and adaptive immunity by influenza subtype and lineage because of the same behavior modes and background of non-adaptive immunity in the same regions and seasons. we propose a hypothesis: under humid and hot condition the dominant transmission mode(s) for a(h n )pdm , b/victoria and b/yamagata might have reduced efficiency, however, there could be effective transmission mode(s) for a(h n ) and pre- a(h n ) virus. some experimental studies were performed to establishing a causal link between humidity, temperature and influenza virus survival/transmission. transmission of influenza a (h n ), a(h n )pdm , b/victoria and b/yamagata virus by respiratory droplets or aerosols in the guinea pig model proceeds most readily under cold, dry conditions. low humidity and temperature increased the stability of influenza virus in aerosols and on surfaces. furthermore, aerosol transmission of a (h n ) virus in the guinea pig model was almost completely blocked at °c, but contact transmission of a (h n ) virus seemed to be efficient at different level of humidity and °c. it remains unclear if high temperature and humidity levels have effect on aerosol and contact transmission of pre- a(h n ), a(h n )pdm , b/victoria and b/yamagata virus among hosts and their stability on surfaces. of note, an experimental study found the survival durations of a(h n ) strains on swiss banknotes were significantly longer than pre- a(h n ) and b/victoria virus. further studies are needed to understand how efficient are these transmission modes for different influenza subtypes or lineages, which is/are dominant mode(s) of transmission among hosts, and which of potential mechanisms is at play under humid and hot condition. one of our findings was the mutual inverse association between a(h n ) and a(h n )pdm epidemics, which provided the evidence on interference between the two influenza a subtypes perhaps possibly due to multiple immune mechanisms. however, our study showed b/yamagata epidemics were positively correlated with a(h n ) epidemics, suggesting b/yamagata epidemics across over study years that were weak could get well along with simultaneous weak h n epidemics. understanding of influenza seasonality is important to define optimal timing of influenza vaccination campaigns. our study indicated that a(h n ) virus brought about twice-annual epidemics in some years in mid-latitude chinese provinces and more frequent summertime epidemics in southernmost chinese provinces, which questions if a single annual influenza vaccination campaign starting in october can offer optimal protection against summertime epidemics of a (h n ) virus in mid-latitude and southernmost chinese provinces. in recent years, it has been reported that mismatches of a(h n ) virus between the influenza vaccine strains and circulating strains were identified frequently, and vaccine effectiveness of a(h n ) virus declined within - months postvaccination. in conclusion, we identified the heterogeneity of seasonality pattern of pre- a(h n ) or a(h n ) virus in three epidemiological regions of china, and different environment predictors for influenza subtypes and lineages in the southernmost provinces. further work should focus on understanding difference in virus survival, transmission by influenza subtype and lineage under humid and hot conditions. bjc has received research funding from medimmune inc. and sanofi pasteur, and consults for crucell nv. the authors report no other potential competing interests. as this study included data from the national influenza surveillance system, ethics approval was not required. not applicable. the datasets at national level analyzed during the current study are available in the world health organization flunet. the datasets with more specific information analyzed during the current study are available in chinese national influenza surveillance informatio system, but they are not open-access datasets. these influenza surveillance data can be available from chinese national influenza center on reasonable request. this study was supported by the national mega-projects for infectious diseases (grant number zx - - ), national natural science foundation of china (grant number ) and emergency prevention and control project of ministry of science and technology (grant number ). the funding bodies had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish. reported in zhejiang in . in this study, we identified ten cases of imported chikv infection in travelers returning to yunnan from southeastern asia in . out of the ten patients with imported chikv infection examined in this study, nine patients had traveled back from myanmar and one patient had travelled back from thailand ( fig. (a) ). all the patients displayed different degrees of symptoms, such as fever, cough, muscle pain, and rash. the details of all the symptoms are shown in table . chikv infection was diagnosed using specific real-time reverse transcription-pcr. serum specimens were collected from the ten patients that tested positive for chikv by real-time pcr analysis, in yunnan between may , and august , . the current study was approved by the medical ethics committee of kunming university of science and technology. written informed consent was obtained from all the participants. a new coronavirus associated with human respiratory disease in china early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia angiotensinconverting enzyme is a functional receptor for the sars coronavirus a pneumonia outbreak associated with a new coronavirus of probable bat origin emergence of sars-like coronavirus poses new challenge in china bat origin of a new human coronavirus: there and back 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chikungunya virus chikungunya virus emergence is constrained in asia by lineage-specific adaptive landscapes this work was supported by henan emergency project for prevention and control of novel coronavirus, the earmarked fund for modern agro-industry technology research system of china (cars- ) and the special fund for henan agriculture research system (s - ). the funders had no role in study de-sign, data collection and interpretation, or the decision to submit the work for publication. we thank jing li and hao-nan wang for the helpful discusses and suggestions. this work is supported by the open research fund of key laboratory of digital earth science ( lde ), and by the fundamental research funds for the central universities under grant no. qd . this work was supported by the national natural science foundation of china ( ) and the guangdong provincial natural science foundation ( a ). we thank le kim thanh, le nguyen truc nhu, and lam anh nguyet for their logistic support. we are indebted to patients for their participations in this study.this study was funded by the wellcome trust of great britain ( /b/ /z and /z/ /z ). supplementary material associated with this article can be found, in the online version, at doi: . /j.jinf. . . . we would like to thank the patients and healthy volunteers in the first affiliated hospital of chongqing medical university for their cooperation and support. this work has been financially supported by national natural science foundation of china (no. and no. ). we thank chinese national influenza surveillance network for contribution in influenza epidemiological and laboratory surveillance. we thank the members of the yunnan international travel healthcare center and kunming changshui airport customs for the data and sample collection. supplementary material associated with this article can be found, in the online version, at doi: . /j.jinf. . . . supplementary material associated with this article can be found, in the online version, at doi: . /j.jinf. . . . recent correspondence in this journal has highlighted the current threat posed by recently-emerging imported chikungunya virus (chikv) in febrile returning travellers. chikungunya fever is infection caused by the chikv and is characterized by fever, arthralgia, myalgia, headache, and rash. chikv belongs to the genus alphavirus within the togaviridae family and is transmitted to humans by the bite of infected mosquitoes-ae. aegypti and ae. albopictus . since the first report of chikv infection in humans in tanzania, intermittent outbreaks have been documented in africa, south america, southern and southeastern asia, and the indian ocean islands; thus, its outbreak has become a global public health problem. to date, three evolutionary distinct chikv genotypes, namely west african (wa), east/central/south african (ecsa), and asian have been identified, based on phylogenetic analyses. a novel lineage of chikv-the indian ocean lineage (iol)-has also been reported, which descended from the ecsa genotype during an outbreak on the island of la reunion between and . recently, it has been reported that iol of chikv has spread to malaysia, singapore, thailand, and indonesia. in china, the first case of imported chikv infection was found in yunnan in . subsequently, several sporadic cases of nonindigenous chikv infection have been described. in , the first outbreak of chikv fever with cases was documented in guangdong. recently, another outbreak of chikungunya fever was table epidemiological information on ten febrile returning travelers infected with chikv in this study. in this study, nine complete genome sequences isolated from serum samples were successfully amplified and sequenced with overlapping fragments, and then the sequence obtained was deposited in genbank under accession no. mn -mn . compared with the nucleotide sequences of the available from the ncbi database, the nine strains shared the highest . - . % nucleotide identity with the east/central/south african lineage strain thail reported previously in thailand, . further, bayesian maximum-clade-credibility tree for full-length nucleotide sequences were constructed using the beast package v. . . . phylogenetic analyses revealed that the ten chikv strains clustered into the homogeneous indian ocean clade of the ecsa genotype ( fig. (b) ).notably, the ten chikv strains isolated from serum samples possessed the mutation k e in the e gene and v a in the e gene; these mutations are associated with significant increase in viral infectivity in ae. aegypti . the strains also possessed g d and i t substitutions in the e gene; these mutations contribute to increased chikv fitness in ae. albopictus. however, the a v mutation in the e gene that is related to significant increase in viral infectivity in ae. albopictus was not observed in any of the strains. in summary, we characterized ten cases of human infection caused by imported ecsa genotype chikv in yunnan, china and successfully isolated nine infectious chikvs from the chikvpositive serum samples. the mutations associated with significant increase in viral infectivity for ae. aegypti or ae. albopictus were also observed in these strains. geographically, the yunnan province is in southeastern china and shares its border with southeast asian countries (laos, vietnam, and myanmar) that are most affected by chikv. with the increase of tourism and trade with southeast asian countries, cases of imported chikv infection are constantly increasing and may have the potential for re-emergence and autochthonous transmission to yunnan. the present study highlights the urgent need for continuous molecular screening and epidemic surveillance for chikv and its vectors to prevent future outbreaks of chikv infection among the human population of yunnan. this work was supported by the national natural science foundation of china (nsfc) ( u ), the reserve talents project for young and middle-aged academic and technical leaders of yunnan province ( hb ), and youth talent program of yunnan "ten-thousand talents program" (ynwr-qnbj- - ). the authors declare no competing financial interests. key: cord- -ndlw gk authors: sultan, ibrahim; habertheuer, andreas; usman, asad a.; kilic, arman; gnall, eric; friscia, michael e.; zubkus, dmitriy; hirose, hitoshi; sanchez, pablo; okusanya, olugbenga; szeto, wilson y.; gutsche, jacob title: the role of extracorporeal life support for patients with covid‐ : preliminary results from a statewide experience date: - - journal: j card surg doi: . /jocs. sha: doc_id: cord_uid: ndlw gk objective: there is a paucity of clinical data on critically ill patients with covid‐ requiring extracorporeal life support. methods: a statewide multi‐institutional collaborative for covid‐ patients was utilized to obtain clinical data on the first critically ill covid‐ patients who required extracorporeal membrane oxygenation (ecmo). results: of the first patients that required ecmo for covid‐ , the age ranged from to years with the majority ( %) being men. seven ( %) had comorbidities. the majority ( %) of patients had known sick contact and exposure to covid‐ positive patients or traveled to pandemic areas inside the united states within the weeks before symptom onset. none of the patients were healthcare workers. the most common symptoms leading to the presentation were high fever ≥ °f ( %), cough ( %) and dyspnea ( %), followed by fatigue and gastrointestinal symptoms (both %), myalgia, loss of taste, pleuritic chest pain, and confusion (all %). all patients had bilateral infiltrates on chest x‐rays suggestive of interstitial viral pneumonia. all patients were cannulated in the venovenous configuration. two ( %) patients were successfully liberated from ecmo support after and days, respectively, and one ( %) patient is currently on a weaning course. one patient ( %) died after days on ecmo from multiorgan dysfunction. conclusions: these preliminary multi‐institutional data from a statewide collaborative offer insight into the clinical characteristics of the first patients requiring ecmo for covid‐ and their initial clinical course. greater morbidity and mortality is likely to be seen in these critically ill patients with longer follow‐up. all patients were on venovenous support, the majority had bicaval configuration. of note, % of patients received the ebola antiviral remdesivir and % received hydroxychloroquine, a substance effective in the treatment of malaria with immunosuppressive and antiviral properties. in addition, % of patients received il- inhibitors for cytokine storm. with this maximal effort, one mortality occurred, two patients were successfully weaned from ecmo and one patient is on a weaning course. with the primary goal of using lung-protective strategy while oxygenating and ventilating adequately. prone positioning was utilized aggressively before the institution of ecmo unless rapid deterioration occurred at which point ecmo was initiated. providing complex therapies such as rescue ecmo during outbreaks of infectious diseases has unique challenges. ecmo is resource-intensive, a scarce resource in times of high demand highly specialized and expensive with the potential for serious complications such as hemorrhage, thrombosis, and propagation of infection. apart from infectious disease outbreaks, ecmo is an evidence-based service, because of the rapidly evolving nature of the disease, no comprehensive report exists in the context of covid- . such data, when reported, would be critical to guide critical care management and the allocation of icu resources and ecmo infrastructure. as the world is bracing for the covid- outbreak preparation should include the provision of ecmo and our report is an attempt at characterizing this novel patient population to aid in the establishment of selection criteria. our report has multiple limitations. first, this is a case series in one state that may not represent what is seen in most of north america. second, since the covid- pandemic has clustered in certain areas when compared to others, ecmo may not be utilized as liberally in highly affected areas with limited resources and personnel. third, these data present an initial experience and do not reflect the complete clinical course of most of these patients. the authors declare that there are no conflict of interests. coronavirus covid- global cases by the center for systems science and engineering clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a singlecentered, retrospective, observational study clinical management of severe acute respiratory infection (sari) when covid- disease is suspected: interim guidance planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases a time to heal: the emprove protocol preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome extracorporeal life support organization. ecls registry report, overall outcomes the role of extracorporeal membrane oxygenator therapy in the setting of type a aortic dissection the role of extracorporeal life support for patients with covid- : preliminary results from a statewide experience key: cord- - v bmbod authors: guo, zhen; sun, lin; li, bailing; tian, rui; zhang, xiaolin; zhang, zhongwei; clifford, sean p.; liu, yuan; huang, jiapeng; li, xin title: anticoagulation management in severe covid- patients on extracorporeal membrane oxygenation date: - - journal: j cardiothorac vasc anesth doi: . /j.jvca. . . sha: doc_id: cord_uid: v bmbod objective: to explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation assisted patients with coronavirus disease . design: this study is single center retrospective observation of a series of patients. participants: laboratory-confirmed severe covid- patients who received venovenous ecmo support from january (th) to may (th), . interventions: this study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ecmo support. results: eight of confirmed covid- patients received venovenous ecmo and had an elevated d-dimer before and during ecmo support. an ecmo circuit pack (oxygenator and tubing) was replaced a total of times in all eight patients and coagulation related complications included oxygenator thrombosis ( / ), tracheal hemorrhage ( / ), oronasal hemorrhage ( / ), thoracic hemorrhage ( / ), bleeding at puncture sites ( / ), and cannulation site hemorrhage ( / ). conclusions: hypercoagulability and secondary hyperfibrinolysis during ecmo support in covid- patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. currently there is not enough evidence to support a more aggressive anticoagulation strategy. acute respiratory syndrome coronavirus (sars-cov- ) has spread rapidly in china and across the world causing a global pandemic, due to its strong transmissibility and virulence , . a majority of coronavirus disease (covid- ) patients have mild symptoms and recover completely; however, approximately - % become severely or critically ill with acute respiratory distress syndrome (ards) requiring intensive care unit (icu) admission . rates of invasive mechanical ventilation among patients admitted to icu ranged from % to % and the mortality rate was about % among patients on mechanical ventilation , . extracorporeal membrane oxygenation (ecmo) could offer life-saving rescue therapy when mechanical ventilation fails to maintain adequate oxygenation in covid- patients. ecmo has been used successfully to manage severe respiratory failure in patients with h n influenza a, h n avian influenza, and middle east respiratory syndrome [ ] [ ] [ ] [ ] . however, there are not many reports describing ecmo support for covid- patients, and littles is still known about the coagulation characteristics of these patients while on ecmo support. inflamed lung connective tissue and pulmonary endothelial cells may result in microthrombi formation and contribute to the high incidence of thrombotic complications in severe covid- , . ecmo could also aggravate the activation of coagulation cascade and consumption of clotting factors causing further coagulation abnormalities. this study aims to summarize the coagulation characteristics, anticoagulation management, and complications of covid- patients who received ecmo support in shanghai, china. all adult patients diagnosed with covid- were admitted to shanghai public health clinical center, a designated hospital for covid- treatment in shanghai and patients were treated by multidisciplinary teams including ecmo experts from different hospitals , . the diagnosis of ards was defined with the berlin definition (three categories of ards were proposed based on the pao /fio ratio) . patients were admitted to the icu if pao /fio < mmhg with high-flow nasal cannula (fio %, l/min). we conducted a retrospective study of eight covid- patients who received venovenous ecmo. the demographics, comorbidities, laboratory results, ecmo-related data and coagulation parameters from the medical records were collected. if there were more than one laboratory tests in the same day, we used the most aberrant values. all the medical data of this study were retrieved from the shanghai public health clinical center and used with permission. standard covid- treatment included protective lung ventilation strategy, optimal peep, sedation, lung recruitment, prone positioning, neuromuscular blockade, and volume optimalization . in cases where a patient showed no substantial improvement, ecmo was initiated according to the protocol at our institution ( figure ). the decision to provide ecmo support should be individualized and based on the risk and benefit assessment for the patient, but there were some absolute contraindications. according to the exclusion criteria used in the ecmo to rescue lung injury in severe ards (eolia trial) and elso guideline for covid- , , absolute contraindications for venovenous ecmo in our center included: prolonged high ventilatory pressures (i.e. end inspiratory plateau pressures > cmh o for longer than days), an expected difficulty in obtaining vascular access, severe coagulopathy, and any condition or organ dysfunction that would limit the likelihood of overall benefit from ecmo ( disseminated malignancy, severe multiple organ failure and uncontrolled bleeding). venovenous ecmo was adopted as the chosen mode to improve oxygen supply and carbon dioxide elimination using the rotaflow ® system (getinge, rastatt, germany) equipped with a quadrox ® oxygenator (getinge, antalya, turkey). ultrasound-guided seldinger technique was used for cannulation of the femoral vein as drainage site and the internal jugular vein as perfusion site. the tip of the internal jugular vein cannula (outflow cannula) was positioned at the junction between right atrium and superior vena cava. the tip of the femoral vein cannula (inflow cannula) was advanced into the right atrium approximately one centimeter beyond the inferior vena cava/right atrium junction and cautions were taken to avoid cannula tip contacting the interatrial septum under echocardiographic guidance. the blood flow ( - ml/kg) and oxygen flow were set according to the pulse oxygen saturation and blood gas results to maintain pao - mmhg and paco - mmhg. point of care ultrasonography for the lungs, heart, abdomen, vasculature and chest x-ray were performed on a daily basis. protective lung ventilation strategy was adopted after ecmo initiation (fio < %, tidal volume - ml/kg, plateau pressure < cmh o, and respiratory rate - times/minute). ventilator parameters and electrical impedance tomography were closely monitored. when necessary, continuous renal replacement therapy (crrt) was performed using the port on the ecmo oxygenator. after march nd , , antithrombin (at) activity monitoring was added, and thromboelastography was used whenever necessary to assess coagulopathy status. when the heparin dose exceeded u/kg/hr, the possibility of heparin resistance was considered. due to the lack of commercial antithrombin agents in china, fresh frozen plasma was supplemented at the dose of - ml/d according to volume status when antithrombin activity was lower than %. platelets were infused when platelet count was less than × /l. if there was significant drop in platelet counts after continuous heparin infusion, heparin-induced thrombocytopenia was highly suspected. after confirmed by t score and anti-pf /heparin antibody test, argatroban was used at a dose of . - . μg/kg/min, and the target of act and aptt was the same as that of heparin. when there was significant thrombosis within the oxygenator, accompanied by d-dimer> μg/ml, fibrinogen< . g/l, and a sustained decrease in platelet count, we replaced the entire ecmo circuit pack ( oxygenator and tubing ) despite satisfactory gas exchange function. in the context of bleeding, secondary hyperfibrinolysis and fibrinogen consumption, tranexamic acid ( - mg/kg via slow injection; followed by a dose of , mg/d at the rate of - mg/kg/hr for - days) and fibrinogen (at - g/d until fibrinogen > . g/l) were infused. if there was significant bleeding or need for invasive procedures, heparin was reduced or suspended for a short period of time until act fell below s and we transfused blood products if necessary. as described in our previous study, weaning of ecmo was started when improvements were observed on chest x-ray/ct, arterial blood gas, respiratory mechanics, and other indicators . the sweep to flow ratio was maintained at : and ecmo flow was gradually reduced to . l/min while continuing the same mechanical ventilation parameters. with the ecmo flow maintained at . l/min, the ecmo sweep was gradually reduced until there was complete cessation of the sweep. in order to take patients off ecmo, the following criteria were maintained for - hours at ecmo flow rates of . l/min without sweep: ① stable hemodynamics; ② significant improvements in ventilation and gas exchange functions, as evident by chest x-ray, ct, electrical impedance tomography and pulmonary ultrasound; ③ pao /fio ＞ mmhg, pco ≤ mmhg, rr ≤ ; ④ body temperature＜ ℃; ⑤ murray index＜ ; ⑥ hct> %. table summarized the outcomes of eight ecmo supported patients included in this analysis. patient received ecmo initially on january th , for eight days and was weaned off. his condition deteriorated on february th , and ecmo had to be restarted again. he died of a pneumothorax and severe bleeding complications ten days after the reintroduction of ecmo support. three other patients died of persistent worsening lung consolidation, which was difficult to reverse, and suffered secondary lung infections with multiple drug-resistant bacteria. patient , , and were successfully weaned off ecmo upon meeting the weaning criteria after days, days, and days respectively and they were discharged by th may . patient was successfully weaned off ecmo and still on rehabilitation treatment. of the eight patients, six developed acute kidney injury and required crrt. the ages of patients ranged from - years, and the body mass index ranged from . - . . prior to ecmo, mechanical ventilation duration was between hours to days, and the pao /fio ratio was less than ( - ) for all patients. our previous report and table provide detailed clinical data of demographics, laboratory results, ventilator parameters and ecmo-related data for each patient. all patients were sedated and provided with analgesics (rass <- ) during ecmo. as indicated by the coagulation parameters in table , most patients had an elevated d-dimer following an expert consensus statement and guideline from shanghai and the united states, our center has provided venovenous ecmo support to eight patients as of may th , , . traditional ecmo indications might lead to prolonged hypoxia and multiple organ failure in covid- patients. therefore, we adopted early ecmo support when mechanical ventilation was insufficient to correct hypoxia in these patients . in this study we found that the clinical characteristics of covid- patients were different from those of other viral pneumonia patients in terms of ecmo anticoagulation management and coagulation-related complications. severe covid- patients manifested abnormal inflammatory responses and immune system damages, characterized by the rise of il- levels and the decline in lymphocyte count, which is correlated with the severity of the pneumonia. , . all eight critically ill patients on ecmo in our study exhibited a cytokine storm syndrome with high il- levels. as other reports described, the inflammatory storm could activate the coagulation cascade and cause secondary hyperfibrinolysis, or disseminated intravascular coagulation (dic) in severe covid- patients [ ] [ ] [ ] . it has become evident from published evidence that sars-cov- infection itself promotes immunological response, unseen with seasonal influenza in addition, supra-physiological shear stress and interactions between foreign material and blood components during ecmo cause systemic activation of coagulation and inflammation pathways that, in extreme conditions, may lead to thrombosis and dic figure . shortly after replacement, oxygenator thrombus was observed again in most patients and often accompanied by d-dimer and fdp near limit values (fdp> μg/ml and d-dimer level> μg/ml, respectively). in a standardized anticoagulation regimen with act maintained at around s, frequent oxygenator thrombosis events and hyperfibrinolysis were rarely seen in previous ecmo-supported patients . in a retrospective study of covid- patients, wu et al. found that the rise of d-dimer level was an independent risk factor of death . in another multicenter retrospective cohort study, elevated d-dimer levels were strongly associated with in-hospital death, even after multivariable adjustment . however, whether or not this is associated with poor prognosis in ecmo supported covid- patients still needs further research. according to granja t et al., activation of gpiib/iiia and increased release of platelet microparticles in venovenous ecmo suggested that ards-related inflammatory responses may lead to activation of platelets and enhancement of fibrin polymerization, which may promote thrombosis . consumption of coagulation factors following thrombosis events was obvious. the need for fresh frozen plasma at the dose of - ml/day and platelets at an average of . u/day to restore coagulation function was necessary in our patients. in cases of oxygenator thrombosis with d-dimer > μg/ml, fibrinogen < g/l, and a drop in platelet count, the entire ecmo circuit pack should be replaced regardless of gas exchange function. in addition to aggressive ecmo circuit pack replacement, we also moderately increased the intensity of anticoagulation and corrected the deficiency of platelets and fibrinogen. if there was only hyperfibrinolysis or dic (international society on thrombosis and haemostasis score > ) without oxygenator thrombosis, we moderately enhanced the coagulation pathway, and provided tranexamic acid therapy. although elso does not recommend conventional antifibrinolytic therapy, we believe it is beneficial for blood protection in hypercoagulation status antithrombin plays an important role in the continuous endothelial activation because it is more exposed on the endothelium when the cells are activated, and it is more released in the blood with consequent rapid consumption with the use of high dose heparin . in ecmo patients, acquired antithrombin deficiency is a result of hemodilution, initiation of coagulation cascade, and consumption due to the use of heparin. antithrombin supplementation is necessary to restore adequate anticoagulation. criteria for antithrombin supplementation in adult ecmo patients are not well defined. while antithrombin is frequently exogenously supplemented to restore therapeutic anticoagulation, when antithrombin activity is deficient, this practice varies widely among institutions. one concern about supplementing antithrombin in the presence of large doses of heparin was increased risk of bleeding . after march nd , , antithrombin activity level was obtained in our center and antithrombin supplementation using continuous infusion plasma was recommended due to the lack of commercial antithrombin recombinant product in china. the effect of plasma therapy was unsatisfactory at - ml/d, and most patients had a low antithrombin level during ecmo support. our goal for antithrombin was at least % of normal values. this study is a single-center study based on a small number of cases. the coagulation properties of ecmo support in this cohort may not be representative, so more comprehensive clinical studies are needed to confirm these findings. in summary, hypercoagulability and secondary hyperfibrinolysis during ecmo support in covid- patients were common and possibly increased the propensity for thrombotic events and oxygenator membrane failure. careful management of the anticoagulation regimen, along with the recruitment of highly experienced teams is necessary. there is insufficient evidence to support a more aggressive anticoagulation regimen currently for covid- patients on ecmo support. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. the authors declare the following financial interests/personal relationships which may be considered as potential competing interests. a novel coronavirus outbreak of global health concern covid- pandemic: global epidemiological trends and china's subsequent preparedness and responses characteristics of and important lessons from the covid- ) outbreak in china: summary of cases 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prognosis in patients with novel coronavirus pneumonia gross examination report of a covid- death autopsy prevention and treatment of venous thromboembolism associated with coronavirus disease infection: a consensus statement before guidelines thrombosis and coagulopathy in covid- patients requiring extracorporeal membrane oxygenation mesenchymal stem cells may ameliorate inflammation in an ex vivo model of extracorporeal membrane oxygenation bleeding, thrombosis, and transfusion with two heparin anticoagulation protocols in venoarterial ecmo patients risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study multi-modal characterization of the coagulopathy associated with extracorporeal membrane oxygenation pathogenesis, diagnosis, and management of disseminated intravascular coagulation: a literature review extracorporeal membrane oxygenation-induced fibrinolysis detected by rotational thromboelastometry and treated by oxygenator exchange hemorrhage under veno-venous extracorporeal key: cord- -ege j lf authors: le breton, c.; besset, s.; freita-ramos, s.; amouretti, m.; billiet, p.a.; dao, m.; dumont, l.m.; federici, l.; gaborieau, b.; longrois, d.; postel-vinay, p.; vuillard, c.; zucman, n.; lebreton, g.; combes, a.; dreyfuss, d.; ricard, j.d.; roux, d. title: extracorporeal membrane oxygenation for refractory covid- acute respiratory distress syndrome date: - - journal: j crit care doi: . /j.jcrc. . . sha: doc_id: cord_uid: ege j lf nan recent studies suggest a survival benefit from extracorporeal membrane oxygenation (ecmo) in patients with severe acute respiratory distress syndrome (ards) [ , ] . however, the role of ecmo remains uncertain for covid- -related ards [ ] . this stems from the fact that very high mortality rates have been reported in covid- patients treated with ecmo. in a study on critically-ill patients with sars-cov- pneumonia, six patients received ecmo of whom five died and one was still on ecmo at the time of publication [ ] . in another study on patients, ten patients received ecmo. at the time of publication, three patients had died whereas five out of seven were still on ecmo [ ]. in another study describing critically-ill covid- patients treated with ecmo, five patients died [ ] . finally, in a report on eight patients treated with ecmo, only three were weaned from the device but were still mechanically ventilated at the time of publication whereas four died and one was still receiving the technique [ ]. these results tend to suggest that patients treated with ecmo during severe covid- related ards have a poor prognosis. this in turn questions the role of this invasive and expensive treatment. our experience markedly differs as we observed a much better prognosis for patients placed table . median saps score on admission was (range to ). all patients had both bilateral diffuse ground-glass opacities and alveolar confluent opacities on chest xray. median duration of mechanical ventilation before ecmo implantation was days. median value of pao /fio ratio before ecmo initiation was . median tidal volume was . ml/kg of predicted body weight and median positive end-expiratory pressure cmh o. despite the application of a low tidal volume, median plateau pressure was cmh o and median driving pressure cmh . all patients were hypercapnic (median mmhg, range to ). implantation of ecmo allowed for implementation of lung ultraprotective ventilation. indeed, plateau pressure was set below cmh , with a positive end-expiratory pressure between to cmh . this resulted in a median tidal volume of . ml/kg of predicted body weight. the median output of ecmo was l/min after implantation with a median sweep gas flow rate of . l/min. seven major adverse events occurred in four patients ( table ) . three major hemorrhagic events (hemothoraxpatient # , intra-peritoneal hemorrhage -patient # , diffuse hemorrhage from cannulas and oropharynx -patient# ) required massive transfusion. two enterococcus faecalis bacteremia (one complicated by mitral endocarditis) resulted from infection at a cannula-insertion site (patients # and # ). two circuit changes were j o u r n a l p r e -p r o o f required: one for device thrombosis and pump dysfunction (patient # ) and one because of severe circuit-related thrombocytopenia (patient # ). all patients were weaned from ecmo after a median of days (range to ). two patients died while still on mechanical ventilation. one was a -year-old jehovah's witness (patient# ). this fact was unknown at the time of implantation. it was later found that the patient had expressed his refusal of transfusion in a written document. his spouse (trusted person) repeatedly refused that her husband be transfused. severe bleeding and hemolysis caused by ecmo resulted in a hemoglobin level of less than g/dl. given the repeated refusal of blood transfusion, decision to withdraw ecmo was done in the hope that the respiratory condition has sufficiently improved to allow for ecmo withdrawal. catastrophic hypoxemia and lung mechanical properties alteration recurred, and he died three days later. improved lung properties and oxygenation allowed for weaning in another patient (patient# ) but he died from cardiogenic shock with massive right ventricular failure seven days later. a diagnosis of pulmonary embolism was suspected but could not be ascertained. as of june th , all surviving patients were weaned from the ventilator after a median duration of mechanical ventilation of days (range to ) and were discharged alive from the icu (table ) specific therapy other organ support extracorporeal membrane oxygenation for severe acute respiratory distress syndrome extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc bayesian analysis of a randomized clinical trial covid- , ecmo, and lymphopenia: a word of caution clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered key: cord- -qry y cx authors: pooboni, suneel kumar title: ecmo in india, swaac elso: challenges and solutions date: - - journal: indian j thorac cardiovasc surg doi: . /s - - -x sha: doc_id: cord_uid: qry y cx the innovations leading to the development of a new technology such as extracorporeal membrane oxygenation (ecmo) and its progress over the years have been inspiring. many great personalities were associated with the genesis and re-designing the multiple essential components of ecmo to make it more biocompatible. we discussed the brief history of cardiopulmonary bypass and ecmo. we elucidated the establishment of a commanding center, extracorporeal life support organization (elso) in the usa, ecmo society of india in the sub-continent and the birth of south and west asia chapter (swac) of elso initially, which became south and west asia, africa chapter (swaac) elso later after amalgamation of africa to this sub-chapter of elso. history of development of cardiopulmonary bypass technology and extracorporeal membrane oxygenation (ecmo) help us understand the changes in medical science over the last century. based on the principles of cardiopulmonary bypass, with the added advantage of addition of heparin to aid in anticoagulation, helped the science of ecmo to move towards wider applicability. further developments in improving the designs of the essential components of ecmo (membrane oxygenators, pumps, biocompatibility issues, miniaturization) over the years helped in wider acceptance besides making the practice of ecmo safe. we described the evolution of the ecmo practices and the organizations safe-guarding the practice of ecmo over the globe. extracorporeal life support organization (elso) was established in at ann arbor, mi, usa. description of elso is not complete without mentioning the history of ecmo. the science of ecmo developed over the past decades. the origins of cardiothoracic surgery and ecmo share their roots together. the thoughts about invention of a mechanical circulatory support system have developed over the years. many researchers put their efforts together in building this life support system. dr. john gibbon was one such inspiring personality [ ] . he was a research fellow at harvard medical school, usa in . the surgical team under dr. churchill performed pulmonary embolectomy on a patient after she developed massive pulmonary embolism [ ] . as a fellow, dr. gibbon looked after the patient during her hospital stay. unfortunately, she passed away. in an effort to find a solution to similar problems, dr. gibbon struggled to develop a mechanical device which could look after the function of lungs until the patient recovers. in , following his work along with his wife mary gibbon, he performed the first successful open-heart surgery on an atrial septal defect (asd) patient [ ] . this was the first cardiopulmonary bypass procedure in history. as the subsequent patients died, dr. gibbon was disappointed with his machine. later, together with mayo collaboration, they made the mayo-gibbon heart-lung machine, leading to many more success stories. further developments were added by enthusiastic physicians such as john kirklin at the mayo clinic and c. walton lillehei at the university of minnesota and dr. theodor kolobow at the national health, lung, and blood institute at the nih, bethesda, maryland, just to name a few. as a result of the contributions of many more dedicated researchers and clinicians, the safety standards of today in the practice of ecmo could be seen as a reality. they contributed to further advances in design, development of biocompatible membrane oxygenators, circuit, etc. in , dr. donald hill, a cardiac surgeon, used ecmo for saving an adult following road trauma with aortic rupture. further success in adult patients could not be claimed for the next few years. in , dr. robert bartlett successfully used ecmo in a newborn following meconium aspiration syndrome to treat lung failure. this was the baby of a poor immigrant mother from mexico. the baby was named esperanza by the nurses, meaning "hope" in spanish. her success story was the initiation of ecmo in the neonatal population. treating further patients on ecmo over the next couple of decades resulted in variable outcomes. dr. robert bartlett trusted the principle of ecmo and continued it as a therapeutic modality. further randomized controlled trials in the uk and usa established the role of ecmo in cases of reversible lung or cardiopulmonary failure as a support mechanism for varying periods of time. with the noble idea of establishing an organization to share the knowledge and developments in the field of ecmo, dr. robert bartlett and his associates established elso [ ] . the first conference was held in ann arbor, mi, usa, in . the extracorporeal life support organization (elso) is a nonprofit organization consisting of professionals and scientists who are involved in doing and researching ecmo. physicians and surgeons from many interested centers in the usa and europe came together under one umbrella. elso maintains a registry of both facilities and specialists trained to provide ecmo services [ ] . elso also maintains registry information of different clinical conditions treated on ecmo in great detail and helps in analysis of these results in an anonymous way to maintain the confidentiality of different centers. table shows the international registry data including the number of cases done in neonatal, pediatric, and adult populations. it also depicts the growth of elso-registered centers worldwide. the elso registry data will be of great help for other clinicians to understand if they contemplate putting a patient with similar condition on ecmo. the data is used to support clinical research, regulatory agencies, and individual elso centers. elso provides educational programs for active centers as well as for facilities who may be involved in the transfer of patients to higher levels of care [ ] . there are different sub-committees such as registry development committee, scientific oversight committee, and registry quality committee. elso website provides resources for prospective centers in the form of policies and procedures and guidelines. elso publishes the ecmo manual and the text book, traditionally called the redbook. the advantages of having a worldwide organization and the unique aspects of a scientific group with representation from all healthcare professional participants in the activities of the organization are very useful for the growth and standardization of ecmo practices. mr peter rycus has been the executive administrator of elso. elso also provides small research grants which can be used to facilitate registry projects. elso has been useful to ecmo centers and practitioners worldwide in several ways. the worldwide registry is available for quick reference, documentation, publication, and quality assurance for member centers. elso has served as the communications center for ecmo-related information. until , there was only central (american) elso. the organization has realized the need for covering the rest of the parts of the world besides the usa, which subsequently lead to the creation of sub-chapters., viz., euro elso, asia pacific elso, latin american chapter of elso, and south and west asia, africa chapter of elso. south and west asia chapter of elso (swac elso) [ ] was established in the year as a result of combined efforts of the members of ecmo society of india and extracorporeal life support organization, elso. ecmo society of india (esoi) was established in with the ideals of improving awareness and practice of ecmo in india. it was initiated by two enthusiastic ecmo practitioners, dr. pranay oza and dr. venkat goyal along with interested clinicians from all over the country. the platform was used for improving knowledge about the practice of ecmo, arranging training programs and annual conferences within india. the program was supported by international faculty who have been actively doing and teaching ecmo. between and , the clinicians of ecmo society of india were engaged with elso steering committee members, who aptly proposed the expansion of elso to cover south east asia and west asia part of the globe. on june , at the th ecmo society conference held at new delhi, india, the south & west asia elso chapter was established with me as the founder chairman. member representatives from the participating countries were selected to represent and lead the ecmo activities in their respective countries [ ] . at the time the chapter was founded, there were countries which have been actively doing ecmo besides those who wanted to introduce ecmo as an expansion to their existing critical care/cardiothoracic surgical activities. swac elso stood as a uniting platform sharing the values of elso despite the regional and economic differences, representing unity in diversity. the main intention has been to support and improve understanding and practice of extracorporeal life support systems in the member countries. the first annual conference of swac elso was held at hyderabad, india, from jan to feb . there was enthusiastic participation from member countries with collaboration to learn from each other's experience. figures and are showing the attendees and faculty at the first and second conferences of swac elso. swac elso region in was representative of the following member countries: in , africa was added to the swac region making it swaac (south and west asia, africa chapter of elso). the incorporation of african region increased the number of participating countries to . figure is showing elso-registered centers worldwide. table is showing swaac elso-registered ecmo centers. the initial logo of swac elso in is shown in the figure below: the subsequent logo of swaac elso in after addition of africa is shown below, representing south asia, west asia, and africa: infection has been playing a significant role in deciding mortality on ecmo. bizzaro et al. reported infection rates being highest in the adult vs. the pediatric and neonatal populations ( . vs. . vs. . infections per ecmo days, respectively) and in those requiring extracorporeal cardiopulmonary resuscitation (ecpr) ( . infections per ecmo days) [ ] . prevalence of infection increased with prolonged duration of ecmo duration of ecmo. as the multidrug resistance (mdr) is reported to be high with the local flora, it will be worth looking for strict implementation of safe infection control precautions and antibiotic stewardship programs to keep the emergence of mdr strains low. south asia, west asia, and africa are special with respect to the challenges offered to the healthcare delivery [ ] . the indications for ecmo have been varying in this geographic region. myocarditis due to scorpion stings, snake bites, supporting patients post poisoning like organo-phosphorous poisoning, and exposure to various other poisons such as celphos poisoning are some of the examples. acute respiratory distress syndrome (ards) secondary to malaria, tuberculosis, typhus, dengue, and other newer varieties of viral pneumonias (sars, h ni, mers, h n , h n , etc.) offer exciting opportunities for application of this life-saving modality. controlling drug-resistant infections is a priority for the successful run of ecmo. other challenges also exist like the lack of ideal transport facilities in most of the countries. cardiac ecmo as extended cardiopulmonary bypass is practiced much more widely than respiratory ecmo. these are huge challenges, yet interesting avenues to discover innovative methodology resulting in improvements in healthcare throughout the world. ecmo is one of the high-cost therapies as much of the disposable equipment has to be imported. with innovations in healthcare and manufacturing cannulae, circuits, and oxygenators locally, it is possible to bring down the cost of ecmo therapy. for entrepreneurs to invest in the manufacturing sector, they should be assured of a high volume of cases. once the number of ecmo centers increases and swaac countries come together with mutual co-operation, it is possible to offer ecmo for reasonable cost. swaac elso consists of centers which provide ecmo as part of national health service as well as those in developing countries offering ecmo on selffunding. meanwhile, exploring several paths for procuring finances such as effective utilization of the available funds, healthcare insurance schemes made affordable to majority of population by increasing awareness, private healthcare schemes provided by the corporate sector, crowdfunding, healthcare charities, and to some extent, personal funding should help in making the life-saving healthcare options such as ecmo affordable to upper and middle income group families. it would be worthwhile for government-funded/autonomous apical institutions to adopt this technology in a cost-effective way as they have the resources and man power available freely. covid- is posing significant problems to healthcare infrastructure in the entire world. elso community unanimously agreed that in a pandemic, healthcare resources should be targeted for proving the essential basic healthcare for the affected people [ ] . ecmo, as a resource intensive therapy, should be applied in carefully selected patients with the greatest chance of benefit from receiving ecmo in centers with sufficient expertise and capacity to do so safely. we are still learning the different ways in which this disease affects humans. until june , out of patients placed on ecmo in the swaac region, survived (personal communication dr. ahmed rabie). swaac elso member countries played their role in extending ecmo support to the needy at the right point of time along with the sister chapters of elso. lastly, becoming an elso member would be useful for the ecmo practitioner and the institution to self-regulate themselves and keep the standards upheld. by analyzing our own data in a confidential manner and comparing it with the international scenario will help in acknowledging our merits and demerits, thereby helping the institutions to audit their performance. it also helps in updating our knowledge, promotional offers to uplift our units and compete for the best ecmo center of excellence awards. the fees for corporate elso membership are also reasonably priced according to the world bank rankings of economies of the countries. table is showing swac elso-registered indian centers as on july . we encourage individual ecmo centers to become elso members. advances in the heart-lung machine after john and mary gibbon fifty years of open-heart surgery part . the development of the first successful heart-lung machine extracorporeal life support organization -wikipedia https://en. wikipedia.org › wiki › extracorporeal_life_support_organization extracorporeal life support organization -ecmo and ecls > excellence > vision. www.elso.org elso: past, present and future infections acquired during extracorporeal membrane oxygenation in neonates, children, and adults an indian perspective, challenges and opportunities interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments my sincere thanks to mr. peter rycus for giving permission to share elso data.funding no funding was received.data and/or code availability and author's contribution statements the paper is a brief description of history of cardiac surgery/elso and personal experiences. for information regarding elso, permission was taken from mr. peter rycus, executive administrator, elso and was acknowledged in the manuscript. ethics approval our paper does not need ethics approval as the subject is the history of two organizations. the author declares that he has no conflict of interest. key: cord- -dlwph za authors: alshahrani, mohammed s.; sindi, anees; alshamsi, fayez; al-omari, awad; el tahan, mohamed; alahmadi, bayan; zein, ahmed; khatani, naif; al-hameed, fahad; alamri, sultan; abdelzaher, mohammed; alghamdi, amenah; alfousan, faisal; tash, adel; tashkandi, wail; alraddadi, rajaa; lewis, kim; badawee, mohammed; arabi, yaseen m.; fan, eddy; alhazzani, waleed title: extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus date: - - journal: ann intensive care doi: . /s - - -x sha: doc_id: cord_uid: dlwph za background: middle east respiratory syndrome (mers) is caused by a coronavirus (mers‐cov) and is characterized by hypoxemic respiratory failure. the objective of this study is to compare the outcomes of mers-cov patients before and after the availability of extracorporeal membrane oxygenation (ecmo) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. methods: we collected data retrospectively on mers-cov patients with refractory respiratory failure from april to december in intensive care units (icus) in saudi arabia. patients were classified into two groups: ecmo versus conventional therapy. our primary outcome was in-hospital mortality; secondary outcomes included icu and hospital length of stay. results: thirty-five patients were included; received ecmo and received conventional therapy. both groups had similar baseline characteristics. the ecmo group had lower in-hospital mortality ( vs. %, p = . ), longer icu stay (median vs. days, respectively, p < . ), and similar hospital stay (median vs. days, p = . ). in addition, patients in the ecmo group had better pao /fio at days and of admission to the icu ( vs. , and vs. , p < . ), and less use of norepinephrine at days and ( vs. %; and vs. %, p < . ). conclusions: ecmo use, as a rescue therapy, was associated with lower mortality in mers patients with refractory hypoxemia. the results of this, largest to date, support the use of ecmo as a rescue therapy in patients with severe mers-cov. middle east respiratory syndrome (mers), which was first described in , is caused by a novel coronavirus (mers-cov). the world health organization (who) as of december reported confirmed cases of the mers-cov infection globally with an overall mortality rate of % [ ] . the majority of cases were reported in saudi arabia, wherein were confirmed cases, and of which ( %) died [ ] . human coronaviruses were first identified in the mid- s and usually cause mild upper-respiratory tract illness. in , the first confirmed case of mers-cov was reported from saudi arabia [ ] . mers-cov infection is associated with significant mortality related to the virulence of the virus, nature of the disease, and the lack of effective therapy. patients with mers-cov who develop acute respiratory distress syndrome (ards) are at a high risk of dying from refractory hypoxemia, multiorgan failure, and septic shock [ ] . current interventions such as lung protective ventilation, prone ventilation, and neuromuscular blocking agents have been shown in randomized trials to improve mortality in patients with ards [ ] [ ] [ ] . however, in some patients, these conventional measures fail to maintain adequate oxygenation; therefore, other rescue therapies are considered, such as different modes of ventilation, inhaled pulmonary vasodilators, and extracorporeal membrane oxygenation (ecmo). anticipated difficulties in patient recruitment, study design, and ethical concerns affect the feasibility of conducting randomized clinical trials that examine the efficacy of ecmo in this population. therefore, observational studies are a reasonable alternative. in this study, we aim to describe the effect of ecmo rescue therapy on patient-important outcomes in patients with severe mers-cov. in response to the large mers-cov outbreak, the saudi ministry of health implemented a national ecmo program in april . the saudi ecmo program provided a rapid transportation chain system (medevac system), isolated intensive care unit (icu) beds, and venovenous (v-v) ecmo machines in selected centers across the country. an ecmo team was created that was available h a day/ days a week. the team included an intensivist trained in ecmo, a cardiac surgeon, a perfusionist, and ecmo-trained nurses. the intensivist on the ecmo team triaged all calls from other centers based on predefined criteria, wherein patients were predetermined to be candidates to receive ecmo or not. criteria for eligibility to receive ecmo were based on the extracorporeal life support organization (elso) [ ] guidelines and are listed below. we retrospectively identified patients who would have been eligible for ecmo but did not receive it because the ecmo program was not available at that time (prior to april ). the intervention (ecmo) group was included from five main ecmo centers in three major cities in saudi arabia after the program initiation (april to december ). all participating hospitals were accredited by the joint commission international and had closed icus with -h coverage by trained intensivists. we obtained ethics approval from the saudi ministry of health ethics review board and from individual centers' ethics boards. patients were candidates to receive ecmo if they have met the following criteria: the ecmo group included patients who met the above criteria and received ecmo after implementing the ecmo program from april to december . we included all patients with mers-cov who received ecmo during that period. the control group were patients who met the above criteria but did not receive ecmo in the period prior to the introduction of ecmo program (prior to april ). weaning from ecmo was primarily based on clinical improvement demonstrated by adequate oxygenation and gas exchange shown in vital signs, blood gases, and chest x-ray. the decision for readiness of a patient to be weaned from ecmo was left to the judgment of treating clinician and the ecmo team. the weaning process followed the elso criteria as follow: weaning starts by decreasing the flow to l/min while keeping the sweep of % (to maintain spo > %). if spo remains within target, a trial of clamping the catheters and keeping the patient on the ventilator at appropriate settings was attempted. we designed an electronic pretested data abstraction forms; the forms were pilot tested prior to data collection to ensure accuracy and reproducibility. trained personnel collected the data at each participating center under the supervision of the local principal investigators. research personnel collected data on patients' demographics, comorbidities, acute physiology and chronic health evaluation ii (apache ii) score, laboratory results (hemoglobin concentration, white blood and platelets counts, kidney function, blood gases), ventilator modes and settings, interventions used to treat refractory hypoxemia (prone ventilation, use of neuromuscular blocking drugs, and pulmonary vasodilators), vasoactive support, antimicrobial and antiviral therapy, steroid use, and primary and secondary outcome data. data were tested for normality using the kolmogorov-smirnov test. a repeated-measures analysis of variance was performed. fischer's exact test was used for the categorical data. independent t test was used to compare the continuous variables in the two groups. the mann-whitney u test was performed to compare the nonparametric values of the two groups. data were expressed as median (interquartile range (iqr) [range]), number (proportion), or mean (sd) as appropriate. the volume of cases was not enough to allow a priori power analysis. however, a post hoc power analysis indicated that the current sample size of patients is powered to detect % absolute difference in mortality rate, with a type i error of . and a power of %. a value of p < . was considered statistically significant. eighty patients with confirmed mers-cov infection were admitted to the icus of participating centers from april to december . thirty-five patients met our eligibility criteria and were included in the analysis, in the ecmo group and in the control group. as shown in table , the baseline characteristics were similar in both groups; the median ages were ( vs. years), and mean apache ii score ( vs. ) were not statistically different. (p = . and p = . ; respectively). adjunctive therapies were used in both groups. ribavirin was used significantly more often in the ecmo group compared to the control group ( vs. %, p = . ), interferon was also used more in the ecmo cohort compared to controls ( vs. %, p = . ), and the use of steroids was similar in both groups ( vs. %, p = . ). at day one of eligibility to ecmo, more patients in the control group required hemodynamic support with norepinephrine compared to ecmo group; however, both groups had similar use of epinephrine and dobutamine, continuous renal replacement therapy (crrt), modes of ventilation, positive end-expiratory pressure (peep), and neuromuscular blocking agents (tables and ). alveolar recruitment maneuver was used in one patient in the ecmo group. none of the patients received prone ventilation. throughout days - , more patients in the control group developed renal impairment and had significantly lower pao /fio ratio (table ) . other laboratory values were similar between both groups (table ). however, due to the small sample size, it was not feasible to adjust for all confounding factors. in the ecmo group, the v-v mode was used in all patients via the percutaneous cannulation approach for vascular access. femoral-femoral access was used in % of patients, while femoral-jugular access was used in % of cases. ecmo access was inserted by a cardiac surgeon in % of cases and by a cardiac intensivist in the remaining %. chest x-ray was used to confirm successful cannulation in patients and transesophageal echocardiography (tee) in one patient. blood flow (l min − ), revolutions per minute, and sweep gas among ecmo patients had a mean (sd) of . ( . ), . ecmo-related mechanical complications occurred in ( %) patients; one patient developed pneumothorax that was treated with chest tube insertion, and two patients had major bleeding immediately after the initiation of ecmo. compared to the control group, the ecmo group had significantly lower in-hospital mortality ( vs. %; p = . ), longer icu stay ( vs. days; p = . ) ( table and fig. ). less use of norepinephrine at days and (p < . ), and better oxygenation (higher pao / fio ratio) throughout days - (table ). in this retrospective cohort study, we found that ecmo rescue therapy was associated with lower in-hospital mortality, better oxygenation, and fewer organ failures compared to historical control (usual care) in patients with severe mers-cov. however, the length of hospital stay was the same and a possible explanation is that during the crisis phase, patients were mechanically ventilated in the ward when icu beds are full, and it is possible that this could have contributed to similar stay in hospital in both groups. although elso issued guidelines on the use of ecmo in patients with ards, these guidelines do not address specific disease context, and are difficult to generalize to the heterogeneous ards population. therefore, we conducted this observational study to report on the efficacy and safety of ecmo in patients with severe mers-cov infection. there is a single case report in the literature looking at ecmo in mers-cov patients. guery et al. described the use of ecmo in two patients with acute respiratory failure secondary to mers-cov infection in france, where both patients developed severe hypoxia and increasing oxygen requirements, leading to mechanical ventilation and ecmo use. one patient died, and the other survived after approximately months in hospital [ ] . ecmo use in respiratory failure has been reported with variable survival rates. the first randomized clinical trials (rcts) failed to prove superiority of ecmo over conventional management [ , ] . however, the severe adult respiratory failure (cesar) trial showed improved -month survival in patients who were referred early to an ecmo center [ ] . this was the largest clinical trial to investigate the efficacy of early use ecmo in patients with ards. despite concerns about the trial design and possible differences in steroid use and ventilator strategies, these results contributed to the increasing use of ecmo worldwide. in this study, we observed no significant differences in the use of adjunctive therapies except for ribavirin use in the ecmo group. the benefit of antiviral therapy in mers-cov infection remains unclear. recent korean guidelines published during the mers-cov outbreak in south korea suggested the use of antiviral therapy in patients with severe mers-cov [ ] . in patients with respiratory failure from h n infection who required the use of ecmo, the survival rate varied considerably between studies ranging from to % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . there was a large variation in survival rates, which could be explained by differences in patients' baseline characteristics and severity of illness. in one study, older, obese, diabetic, or immunocompromised patients were found to be at a higher risk of developing severe [ ] [ ] [ ] [ ] . in this study, the two groups were comparable at baseline, and there were no significant differences between groups in any of these variables. another large observational study examined the predictors of death in h n patients who underwent v-v ecmo and found that creatinine and bilirubin levels, systemic arterial pressure, hematocrit, and pre-ecmo hospital length of stay were associated with higher mortality [ ] . another important factor is the center experience and volume of cases; this could have contributed to the variability in survival rates with ecmo use. a recent study by barbaro et al. [ ] demonstrated that centers with > ecmo cases/year had better survival rates than centers with less than cases per year. in saudi arabia, ecmo was not available except in one center until the mers-cov crisis; thereafter, the ecmo program was implemented as a therapeutic option for patients with refractory hypoxemia. ecmo interventions were run in tertiary centers with equipped icus by most experienced intensivists and perfusionists who received training in ecmo prior to the start of the program. although more ecmo patients received ribavirin and interferon therapy, we do not believe that this difference has an impact to our findings. published reports on this therapy are limited, but none showed significant improvement with this combination [ ] [ ] [ ] . the largest study to date published in abstract format [ ] showed no reduction in mortality. therefore, we believe that the imbalance of co-interventions between the two groups is unlikely to affect the estimation of treatment effect. in regard to infection control issues, caregivers safety of ecmo patients was organized and maintained by aggressive measures which were applied strictly and monitored closely with all admissions were taken to airborne isolated rooms which impacted the containment of the virus plus applying the universal protective personal measures all the time during the patients encounter. because of these stringent measures, there were no reports by or about any caregiver of any ecmo patient being affected. to our knowledge, this is the largest study to describe outcomes in patients with mers-cov who received ecmo. there are several strengths to our study: the "before and after" design allowed us to compare ecmo cases to a control group with similar demographics and within the same institutions. we also collected data on important variables and confounders, and conducted adjusted analyses to assess the impact on the results. we adhered to the strengthening the reporting of observational studies in epidemiology (strobe) guidelines [ ] . despite the strengths of our study, it has several important limitations. first, the retrospective nature of this study renders it at risk of bias. all patients in the control group died, which may be explained by the severity of illness, as these were patients who had ards and were eligible otherwise. we cannot rule out the possibility of selection bias, as we were unable to track all transfer requests due to the outbreak and crisis at the time, leaving us with limited information. in addition, some patients were transferred from non-participating ecmo centers; therefore, baseline pre-ecmo data such as blood gases and ventilator settings could not be obtained. furthermore, due to insufficient documentation during the outbreak and crisis circumstances, we were not able to track the ecmo requests to the referral call center. there were differences in some co-interventions (e.g., antiviral therapy), and the influence of unmeasured confounders cannot be excluded. such concerns can only be addressed in rcts; however, conducting rct is likely to be challenging in the context of epidemics. this study was not designed to compare the cost of interventions; although it is an important outcome that could help the clinicians and stakeholders to make decisions. lastly, the small sample size limited our ability to perform an adequate multivariate analysis. similar to other ecmo studies, it is difficult to determine if the mortality was the result of refractory respiratory failure or other causes like septic shock or other organs failure. in summary, the use of ecmo was associated with lower mortality in patients with severe mers-cov infection and refractory hypoxia. future randomized trials, although challenging to conduct, are highly needed to confirm or dispute these observations. until more data are available, ecmo could be considered as a rescue therapy in selected mers-cov patients with refractory hypoxemia. department of icu national hospital, internal medicine and critical care, riyadh, saudi arabia. critical care medicine department isolation of a novel coronavirus from a man with pneumonia in saudi arabia state of knowledge and data gaps of middle east respiratory syndrome coronavirus (mers-cov) in humans ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. the acute respiratory distress syndrome network prone positioning in severe acute respiratory distress syndrome neuromuscular blockers in early acute respiratory distress syndrome assays for laboratory confirmation of novel human coronavirus (hcov-emc) infections clinical features and viral diagnosis of two cases of infection with middle east respiratory syndrome coronavirus: a report of nosocomial transmission randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal co removal for adult respiratory 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meta-analysis including studies and patients receiving ecmo extracorporeal membrane oxygenation for pandemic influenza a(h n )-induced acute respiratory distress syndrome: a cohort study and propensitymatched analysis long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome: single-centre experience with -year follow-up extracorporeal membrane oxygenation for critically ill patients with influenza a (h n )-related acute respiratory distress syndrome: preliminary experience from a single center extracorporeal membrane oxygenation for severe influenza a (h n ) acute respiratory distress syndrome: a prospective observational comparative study extracorporeal lung support in patients with severe respiratory failure secondary to the - winter seasonal outbreak of influenza a (h n ) in spain the italian ecmo network experience during the influenza a(h n ) pandemic: preparation for severe respiratory emergency outbreaks middle east respiratory syndrome coronavirus: a case-control study of hospitalized patients clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection epidemiological, demographic, and clinical characteristics of cases of middle east respiratory syndrome coronavirus disease from saudi arabia: a descriptive study hospital outbreak of middle east respiratory syndrome coronavirus predicting mortality risk in patients undergoing venovenous ecmo for ards due to influenza a (h n ) pneumonia: the ecmonet score. intensive care med association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality. analysis of the extracorporeal life support organization registry ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome oronavirus:an observational study ribavirin and interferon alfa- a for severe middle east respiratory syndrome coronavirus infection: a retrospective cohort study ifn-α a or ifn-β a in combination with ribavirin to treat middle east respiratory syndrome coronavirus pneumonia: a retrospective study effect of ribavirin and interferon on the outcome of critically ill patients with mers the strengthening the reporting of observational studies in epidemiology (strobe) statement: guidelines for reporting observational studies we wish to acknowledge the saudi ministry of health for implementing a national ecmo program in april who assisted us throughout the course of this research. we thank our colleagues from all participating icus throughout saudi arabia who provided insight and expertise that greatly assisted the research, and for their comments on an earlier version of the manuscript. the authors declare that they have no competing interests. all data produced and analyzed during this study are included and presented as tables in this manuscript. authors have no objection in granting and assigning the annals of intensive care journal unrestricted right to reproduce, publish, and distribute this manuscript in all forms including electronic form either offline or online media. no patients were involved neither in the design, recruitment, and conduction of this study nor in the development of outcome measures. we plan to disseminate the results of the study in lay language for patient interest groups. we had one institutional review board approval (irb-h- -j- ) for the ecmo from the saudi arabia ministry of health as all ecmo program during the outbreak was under the umbrella of the ministry. all authors declare that they receive no support from any commercial organization or company. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -muah b authors: kapoor, poonam malhotra title: covid- thrombosis: an unsolved mystery date: - - journal: nan doi: . /s- - sha: doc_id: cord_uid: muah b nan we as critical care intensivists are all endothelioligists, who need to fix the damaged endothelium back to its native form. as new treatment options show a promising rainbow in the near horizon, the darkened sky looks brighter. to quote a few sunny happenings in the sars pandemic, the health ministry of india gave the go ahead on the use of the antiviral drug, remdesivir, in moderate stages of covid- . it has also cleared the air on the controversial antimalarial drug hydroxychloroquine, which according to the indian ministry guidelines, should be used in the early course of the disease and not in the critically ill patient. the advent of moderna, oxford and serum institute of virology vaccine(s) has also, in recent times, cleared key hurdles, such as more virulence by the vaccine and the number of vaccine dosages required. while the data released by the us national institute of allergy and infectious disease (niaid) and moderna offered some assurance on mice trials, the studies do not fully answer many questions. "this is the barest beginning of preliminary information," said dr gregory poland, an immunologist; today, human trials of the vaccine are ongoing-a promise to a cure. despite a massive increase in affected cases after unlocking, the reason for india's low-mortality rate, despite the number of infected crossing over million, relates to the following: a timely lockdown, innate immunity, bcg vaccination at birth, and others, as has been summarized in ►fig. . the milder patients forming to % of population get away with symptoms of fever, fatigue, dry cough, and loose motions. it is in the second and third week of the pandemic that an exponential increase in symptoms of lung infiltrate was observed. it is different from a typical acute respiratory distress syndrome (ards), more like pulmonary fibrosis, which worsens with thrombosis, renal failure, and a dic (disseminated intravascular coagulation) type of presentation. patients immobilized with an active covid- infection are immobile and experience prothrombotic changes. these changes also are seen in vessel walls and thus we see a hyperinflammation syndrome with elevated d-dimer and cd receptors getting activated. the covid- virus directly damages the megakaryocytes and platelets and expresses high-levels of cd . they then invade the hematopoietic stem cells and infect the bone marrow, leading to thrombocytopenia. the cytokine release syndrome ensues in the second week (day - ) and worsens with a rise in ilb , il , il il , and monocyte chemokine i (mcpi) over time. these inflammatory mediators upregulate the expression of vascular endothelial growth factor, particularly il- , which produces more thrombus and fibrinogen. endothelial cells express ace ; thus, covid- aggravates cell damage, upregulates tissue factor expression, and loosens antithrombin, tfpi (tissue factor pathway inhibitor) and protein c. this completely damages the endothelium and the anticoagulation system. the virus attacks β chain and dissociates heme, removing iron and converting it to porphyrin. the virus can dissociate oxyhaemoglobin, carboxyhaemoglobin, and glycosylated haemoglobin. this leads to lung inflammation due to inability of both oxygen and co exchange, producing ground glass capacities on chest x-rays. chloroquine completes the binding to porphyrin, and thus has been seen to be useful in covid- prophylaxis (although controversial). sars-cov- studies show alterations in serum il- , il- , il- , granulocyte-colony stimulating factor, ip- , mcp- , mip -α, and tnf-α, which are positively correlated with covid- disease severity. therefore, larger multiplex panels measuring several markers together are recommended for speed, especially those that are well-characterized for reliability (e.g., meso scale discovery (msd) v-plex assays). the suppression of the "cytokine storm" is very essential in the icu settings of these critically ill patients. clinical trials are underway to treat this "cytokine storm" with a plethora of anti-inflammatory drugs such as hcq, prednisolone, antiviral remdesivir, etc. but with caution, as no definitive treatment has been declared as yet by the who. resting at home and social distancing is the best treatment, as it enables a small army of their own cells to attack the virus, thus preventing viral replication and helping to develop antibodies that prevent it from infecting new cells. these antibodies also provide some protection against reinfection by this covid- virus at a later time. this storm theory could explain the crash that happens in the second week. favipiravir binds to the virus envelope protein with very high affinity, prevents entry into the cells as well as binding of structural protein to porphyrin. the marked elevation of il- in patients with cytokine release syndrome (crs) led to the institution of successful targeted therapy for the treatment of crs using il- receptor blockade (tocilizumab). measuring il- , however, involves a research tool not rapidly available as a clia-approved test in most centers. therefore, the sloan kettering group's observation that levels of c-reactive protein (crp), for which there is a rapidly available test, correlated with crs severity, was a valuable contribution that has since been widely adopted. one important question still to be evaluated is whether earlier intervention with tocilizumab might reduce the morbidity and mortality from crs without jeopardizing the impressive clinical responses of cd car-modified t cells. future research will answer this query soon. it is widely acknowledged that the majority of covid- patients, especially those with severe disease, are characterized by lymphocytopenia. this laboratory symptom is observed mostly in adult patients and much less often in children. notably, the currently available data strongly indicates that lymphocytopenia is dynamically modulated by the intensification of local and systemic inflammation, direct infection of lymphocytes, and destruction of lymphoid organs. in addition, treatment with glucocorticosteroids may cause lymphocytopenia in some cases. support with extracorporeal membrane oxygenation (ecmo) is further not available in many low-and middle-income countries; therefore, ecmo might not seem to gain as much of a priority as personal protective equipment, correct management, diagnosis and quarantine, oxygen therapy alone, and mechanical ventilation in the first instance. an ecmo therapy and covid- itself are associated with certain, often synergistic changes in hematological and inflammatory status of the patients; the efficacy of ecmo is largely dependent on centers' experience with such therapies. where extracorporeal life support (ecls) expertise is available, it should be considered according to the standard management algorithm for ards in supporting patients with viral lower respiratory tract infection. the venovenous ecmo, begun timely, is the right mode of ecmo, with facility for ecco removal as well. patients on left ventricular assist device (lvad) support are particularly vulnerable to infectious complications due to the inherent presence of hardware and driveline exposure as well as the fact that prolonged support has been associated with immune dysregulation. finally, prone ventilation is beneficial in cases of severe ards. the maneuver has been effective in improving lung mechanics and gas exchanges, and in some cases, it may prevent the need to escalate to venovenous extracorporeal membrane oxygenation. although there are no published outcomes, early experience in wuhan, china, indicates that prone position was widely used in patients with covid- related severe ards and had possible benefits. nonetheless, it may be prohibitive in heart failure patients on lvad or ecmo support. prone positioning could result in complications such as compression of outflow graft and driveline, impaired venous return from increased thoracic pressure, hardware malpositioning, and worsening right ventricular (rv) hemodynamics. the rainbow in a clear sky for the covid thrombosis is the issue of jccc, where there are articles by our coagulation experts, prof klaus gorlinger from germany along with dr. ajay gandhi, who elucidate the process of connecting the dots of covid- coagulopathy. how to prepare a covid icu, and the right way to donning and doffing is brought in vivid articles by team of dr. kanchi muralidhar and jose chacko from narayana hrudayalaya, bangalore. the bright team from medanta narrates the management of covid- in the icu. direct news and feelings from the italian epicenter by dr. fabiola sozzi is worth a read as is the article on "covid ecmo myths" along with our regular features-so read on and enjoy the fruits of the dedicated hard work of our authors. in these uncertain times of the coronavirus, where we all are learning to live differently, self-reliance of one's own creativity and hard work is all that we have, which will prove to be a winning streak. this war will be won with perseverance, patience and resilience. teachings from the "bhagvat gita" help us find solace as we face adversity in life in these times of corona. it helps us reminiscence that "we are not the doers but mere seers" and that all changes remain with the almighty." let us continue to persevere as mother nature innately teaches us. none declared. clinical features of patients infected with novel coronavirus in wuhan, china epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study prognostic factors for vte and bleeding in hospitalized medical patients: a systematic review and meta-analysis modified improve vte risk score and elevated d-dimer identify a high venous thromboembolism risk in acutely ill medical population for extended thromboprophylaxis high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study covid- ) update -vaccines and immunity hlh across speciality collaboration, uk. covid- : consider cytokine storm syndromes and immunosuppression current concepts in the diagnosis and management of cytokine release syndrome efficacy and toxicity management of - z car t cell therapy in b cell acute lymphoblastic leukemia covid- ecmo myths busted united states center for disease control interim guidance for clinical management of covid- patients with and without acute respiratory distress syndrome intubation and ventilation amid the covid- outbreak: wuhan's experience key: cord- -u vd tmj authors: kaushal, s.; khan, a.; deatrick, k.; ng, d. k.; snyder, a.; shah, a.; caceres, l. v.; bacallao, k.; bembea, m.; everett, a.; zhu, j.; kaczorowski, d.; madathil, r.; tabatabai, a.; rosenthal, g.; brooks, a.; longsomboon, b.; mishra, r.; saha, p.; desire, y.; saltzman, r.; hankey, k. g.; arias, s. a.; ayoade, f.; tovar, j. a.; lamazares, r.; gershengorn, h. b.; magali, f. j.; loebe, m.; mullins, k.; gunasekaran, m.; karakeshishyan, v.; jayaweera, d. t.; atala, a.; ghodsizad, a.; hare, j. m. title: intravenous mesenchymal stem cells in extracorporeal oxygenation patients with severe covid- acute respiratory distress syndrome date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: u vd tmj background: there is an ongoing critical need to improve therapeutic strategies for covid- pneumonia, particularly in the most severely affected patients. adult mesenchymal stem cell (msc) infusions have the potential to benefit critically ill patients with acute respiratory syndrome sars-cov- infection, but clinical data supporting efficacy are lacking. methods: we conducted a case-control study of critically ill patients with laboratory-confirmed covid- , severe acute respiratory distress syndrome (ards). to evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ecmo) support. patients (n= ) were administered with up to infusions of intravenous (iv) mscs and compared to a local ecmo control group (n= ). the primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance. findings: msc infusions ( patients) were well tolerated and no side effects occurred. of ecmo patients receiving msc infusions, out of died ( . %; %ci: . %, . %) compared with a mortality of of ( . %; %ci: . %, . %; p = . ) in the ecmo control group. isolated plasma exosomes containing the sars-cov- spike protein decreased after msc infusions between day or after administration (p= . and p= . , respectively) and was associated with a decrease in covid- igg spike protein titer at same time points (p = . and p= . , respectively). control ecmo patients receiving convalescent plasma did not clear covid- igg over the same time frame. interpretation: together these findings suggest that msc iv infusion is well tolerated in patients with a broad range of severity including the most severe covid- ards requiring ecmo. these data also raise the possibility that mscs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial. introduction: the emergence and spread of the novel coronavirus disease (covid- ) has led to an unprecedented global pandemic ( ) . as of september , , covid- has resulted in over . million cases and ~ , deaths worldwide, and at least . million cases and ~ , deaths in the united states. the mortality largely results from the development of a severe acute respiratory distress syndrome (ards), causing severe fatal hypoxemia, and multisystem organ failure ( ) . the virus affects the respiratory system by binding to the angiotensin converting enzyme (ace- ) receptor, which is constitutively expressed in alveolar cells and vascular endothelium ( ) . infected patients have a nearly universal development of a severe proinflammatory state, reflected by elevated levels of c-reactive protein, interleukin- , ferritin, and other cytokines ( - ) ( ). traditional interventions for inflammatory syndromes have had limited efficacy, and there are no therapeutic agents which prevent or treat ards in covid- patients, although remdesivir has now entered clinical practice based on studies showing reduced hospitalization days ( , , ) . recently, a wuhan study reported that out of hospitalized patients, % developed ards which resulted in a % hospital mortality ( ) . a recent pooled analysis reported as high as % mortality in covid- ards patients, and a reported % mortality in extracorporeal membrane oxygenation (ecmo) covid- patients ( ) . to reduce mortality in the most severe covid- ards patients, mitigating the cytokine storm represents a key strategy. however, many anti-inflammatory drugs have serious sideeffects including the potential to offset immune mechanisms aimed at decreasing the viral load. accordingly, an immunomodulatory therapy, such as the msc, which also possesses anti-viral properties would be highly valuable in the anti-covid armamentarium. mesenchymal stem cells (mscs) possess unique and powerful immunomodulatory characteristics and effectively block cytokine release syndrome in laboratory models ( ) ( ) ( ) . recently in china, intravenous adult mscs have been reported to improve covid- patients . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) since the mscs were administered based on compassionate use, there was no randomization. however, we established a control group for comparison of outcomes and clinical characteristics between the msc-administered subjects and other critically ill ards ecmo patients hospitalized at our local institution with similar baseline characteristics. for our institution, we retrospectively characterized all ecmo covid- patients admitted during the same time period from april , to september , . allogeneic mscs were derived from healthy bone-marrow donors and the samples were > % viable at the time of intravenous injection. patients on ecmo received infusion of allogeneic mscs via the ecmo circuit return cannula (positioned in the right atrium, with the majority of blood directed across the tricuspid valve and into the pulmonary circulation) and non-ecmo patients received the mscs intravenously through a central venous catheter. standard of care infusion was provided for all ards patients on or off ecmo. clinical information for the patients before and after msc infusion and non-msc administered control group admitted at the same time was obtained from a review of the hospital electronic medical system and include the following: demographic data, days of admission from symptom onset, and presenting symptoms; data about various infusions, including mechanical ventilation, ecmo support, antiviral therapies, medications, and steroids; clinical data, including pao /fio , sequential organ failure assessment (sofa) score (range - , with higher scores indicating more severe illness), laboratory data, including blood cultures, white blood cell count, chemistry panels assessing liver and kidney function, viral pcr load, inflammatory factors creactive protein (crp; mg/dl), il- (pg/ml), ferritin (ng/ml) and procalcitonin (ng/ml); data from . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted october , . chest imaging studies; and information on complications, such as ards, ecmo, msc infusion reactions, ventilation, bacterial pneumonia, and multiple organ dysfunction syndrome. since the ecmo blood flow remained constant during support, the oxygen delivery provided by the ecmo circuit remained constant for these patients. therefore, increasing pao /fio ratios or the need to reduce sweep gas flow for these patients is related to improvement in their native lung function. plasma biomarkers were measured at baseline and post-infusion at selective timepoints. ifn-γ, il- β, il- , il- , il- , il- , il- , il- -p , il- , tnf-α, and vegf-a concentrations(pg/ml) were measured using commercial assay (meso scale discovery, gaithersburg, md). to study the imprecision and variability of the biomarker measurements, intraand inter-assay coefficients of variation (cv) were determined. intra-assay cvs tested the variability of biomarker measurements performed in the same sample on the same assay plate. inter-assay cvs tested the variability of biomarker measurements performed in the same sample on different assay plates often used to measure long-term imprecision. when measuring biomarkers with multiplex assays, generally cv's < % are targeted and cvs < % are considered excellent. for the preliminary analysis, all intra-assay cvs were less than % and inter-assay cvs for these biomarkers were < %. sera collected from severe covid- patients following msc iv administration infusion were utilized to detect and quantify sars-cov- spike antigen containing exosomes by immunoblot. exosomes were isolated using ultracentrifugation and the presence of exosomes specific marker cd was validated using immunoblot as previously published ( ) ( ) ( ) . briefly, total exosome protein ( μg) was resolved in polyacrylamide gel electrophoresis, and the proteins were transferred into a polyvinylidene difluoride (pvdf) membrane. the pvdf . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) membrane was blocked with % non-fat milk prepared in x phosphate buffered saline (pbs) and was probed with exosome-specific marker cd ( , biolegend) and sars-cov- spike (gtx , genetex) were used as primary antibodies and goat-anti-mouse conjugated with horse radish peroxidase ( , cell signaling technology) were used as secondary antibody. the blots were washed with x pbs-tween (thermo fisher scientific), developed using chemiluminescent hrp substrate (wbkls , millipore sigma, burlington, ma), and exposed using odyssey clx imaging system (li-cor biosciences, lincoln, ne). the intensity of sars-cov- spike antigen was quantified using imagej software and normalized with cd . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint to assess temporal changes in cytokines associated with msc infusions, we constructed graphs anchoring at the baseline cytokine level (on the x-axis) which was defined as the sample obtained immediately prior to the first msc infusion. we plotted cytokine levels days after the first infusion, or days after the second msc infusion, and days after the third infusion on the y-axis. these days were selected based on availability of data and represent reasonably similar durations from msc infusion to sample collection. all cytokines were plotted in the log scale. to estimate the proportion of samples stable or decreasing after msc infusions, we created a binary response variable based on the post-msc sample being less than or equal to the baseline cytokine level and fit a repeated measures logistic model with an independent correlation structure. for each cytokine, we present the proportion of samples less than or equal to baseline levels with corresponding valid % confidence intervals. the null hypothesis of this single sample test is that this proportion is equal to %. significantly different estimates at the p= . level were shown by whether the % confidence intervals contained the null. to compare risk of death (i.e., cumulative incidence) in the absence of censoring since all were known to have either died or survived to discharge, we present the proportion who died with exact % confidence intervals using the klopper-pearson method among those who supported with ecmo for the who received msc infusions and the who did not receive msc infusions. fisher's exact test were used to compare survival among those who received msc infusions to those who did not locally, and then in comparison with the elso registry. all analyses were conducted in sas . software (cary, nc) and graphs were constructed in r . . (vienna, austria). from april , to september , , we administered mscs under fda eind to patients (n= ; age range, - years; women) who met the inclusion criteria (table ). all msc administered patients had pre-existing complex medical conditions and one was a former . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . smoker (supplement table , ). all had received hydroxychloroquine ( %), none had received antivirals and most received corticosteroids ( . %). nine patients ( %) were supported with venous-venous ecmo. msc infusions were administered between and days after hospital admission. during this period, contemporaneous ecmo patients with covid and similar baseline conditions (table ) did not receive mscs and served as a control group (table ) . no acute-infusion related or allergic reactions were observed within two hours after msc infusion, six patients were successfully decannulated from ecmo on post-msc infusion day , , , , , and days, respectively, and of these, patients required a tracheostomy and patients were discharged home. the two tracheostomy patients had their tracheostomy decannulated. one patient remained on ecmo at the end of the follow-up period, and two patients died on ecmo after msc infusion. two of msc administered patients not on ecmo were extubated and discharged from the hospital with length of stay and days. a third msc administered patient not on ecmo suffered a myocardial infarction that resulted in a left ventricle ejection fraction of %, cardiogenic shock and died on hospital day which was days after msc infusion. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint the sofa score ranged from to prior to msc infusion, and decreased to a range of to at days following infusion (supplement table and figure ). the pao /fio ranged from . to . prior to msc infusion, and increased for most patients ( . %), ranging from to . days after msc infusion (supplement table we next examined the levels of pro-inflammatory and anti-inflammatory cytokines from plasma samples taken at baseline and approximately three days after each msc infusion by examining their ratio of change from baseline and after each msc infusion ( figure , supplement figure ). these samples were grouped as days after first infusion (black; n= ), or days after the second msc infusion (blue, n= ), and days after the third infusion (red, n= ). vegf-a in % of post-msc infusion samples was less than or equal to baseline levels ( % ci: %, %) indicating that vegf-a was increased in % of post-infusion. this was significantly different from the null of % (p= . ). for the remaining cytokines, % to % of samples decreased, apart from il- in which % of the samples decreased. these were not significantly different from the null, except for il- -p in which % were decreased ( % ci: %, %; p= . ). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. in this case-control study, critically ill covid- patients were administered intravenous infusions of culture-expanded allogeneic mscs. in response, inflammatory cytokines declined within days of msc infusion, patients improved clinical status, sofa scores, and pao /fio ratios, and exhibited resolution of covid- pneumonia on chest radiographs. among the sickest cohort requiring ecmo support, mortality was numerically less than that of the global world-wide experienced as tabulated by the registry. of surviving ecmo patients, have been successfully decannulated with one subject remaining on ecmo at study endpoint. these findings, which are preliminary, nevertheless add to other early stage reports, substantiate the safety of these infusions, and strongly support efforts to rigorously test this strategy in placebocontrolled trials. the novel sars-cov virus can induce ards as a serious manifestation of covid- which can rapidly progress to refractory pulmonary failure. in the most advanced cases, ecmo . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . support may be considered as a rescue therapy, with limited prognosis for viral infections in general. for instance, ecmo support for ards in patients with middle east respiratory syndrome coronavirus (mers-cov) reduced the in-hospital mortality rate to % and decreased length of intensive care unit stay when compared to conventional therapy ( ) . however, a pooled analysis of early ecmo support in covid- patients reported a % in-hospital mortality rate as compared to . % with conventional therapy ( ) . query of the extracorporeal life support even so, the major limitation of the latter study is that the covid- patients were not categorized as having severe ards, rather they had at most mild ards. in our study, we administered mscs to patients admitted to hospital with severe ards, in this preliminary series of critically ill patients with covid- pneumonia, most requiring ecmo support, clinical status improved after msc infusion. while this study only reports results from relatively few patients, this experience suggests that a patient population with great unmet need, like ecmo patients, who are often excluded from current clinical trial design should be studied in randomized, placebo-controlled trials. mscs may represent a potentially safe antiinflammatory therapy that can contribute to patient recovery in the most severe forms of covid- pneumonia. drs kaushal and hare had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . infusions table . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . -intubation to ecmo hours, positive end expiratory pressure, stroke, renal failure, renal insufficiency, intracranial hemorrhage, and intubation to ecmo hours was not included for one patient with msc infusion from miami -any patient that was remained in the hospital were not accounted for in the length of hospital admission. -two patients remained on ecmo and was not accommodated in ecmo run time hours -ecmo run time was calculated by the number of days on ecmo times hours . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . table for more complete definition). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . figure . chest radiograph images of the critically severe covid- patients at baseline and interval times after msc treatment. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted october , . clinical features of patients infected with novel coronavirus in wuhan characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention sars-cov- and pathophysiology of coronavirus disease middle east respiratory syndrome: emergence of a pathogenic human coronavirus. annual review of medicine clinical and immunological features of severe and moderate coronavirus disease clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan cytokine release syndrome in severe covid- drug infusion options for the -new coronavirus ( -ncov) compassionate use of remdesivir for patients with severe covid- risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ards) due to coronavirus disease (covid- ): pooled analysis of early reports mesenchymal stem cell-derived factors: immuno-modulatory effects and therapeutic potential mesenchymal stem cell perspective: cell biology to clinical progress comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the poseidon randomized trial aging and disease extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic influenza a (h n ) infection, a hint for covid- infusion nausea/em esis; severe chest pain key: cord- -ekzml r authors: huang, shiqian; xia, haifa; wu, zhouyang; zhao, shuai; yao, shanglong; luo, huilin; chen, xiangdong title: clinical data of early covid- cases receiving extracorporeal membrane oxygenation in wuhan, china date: - - journal: j clin anesth doi: . /j.jclinane. . sha: doc_id: cord_uid: ekzml r • shared early cases on the application of ecmo in severely ill patients with covid- in wuhan, china; • revealed the overall poor prognoses of these patients, probably related to the patients' age, underlying diseases, and the evolution of covid- , etc. • proposed the particularly importance of grasping the indications of ecmo and selecting patients to clinicians, especially during the epidemic. can target the cytoplasmic components of invading lymphocytes to cause their destruction [ ] . in addition, ecmo operation usually causes lymphopenia due to complex immune damage accompanied by activation of extracorporeal circuit. considering the importance of lymphocyte filling for resistance to sars-cov- , the decision of using ecmo should be made more cautiously in covid- patients with significant lymphopenia [ ] . in our report, patient died of sudden respiratory and circulatory failure and patient died due to multiple organ dysfunction. patient , without basic disease, his situation is gradually improving after active treatment. indeed, ecmo can provide respiratory and cardiac support but cannot treat the underlying pathologic condition. in view of high mortality rate of severe covid- patients, ecmo may have certain therapeutic benefits. however, the actual results indicated that the clinical benefits are limited, while the application may increase the medical burden, especially during the epidemic. therefore, we must carefully choose the indications of ecmo. early use of ecmo for younger patients without underlying diseases is the most recommended. ecmo is a complex and high-risk method that may lead to complications such as bleeding, infection, and limb ischemia. it should be done in centers with enough experience, quantity, and expertise to ensure safe use. anyway, ecmo mustn't charge ahead to replace measures such as epidemic quarantine and prevention and control, oxygen inhalation, blood oxygen monitoring. epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ards) due to covid- ): pooled analysis of early reports clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in covid- patients covid- , ecmo, and lymphopenia: a word of caution not applicable. key: cord- -gbbkcwo authors: salazar, leonardo alberto; uribe, juan david; henao, claudia marcela poveda; santacruz, carlos miguel; enfermera, estefanía giraldo bejarano; bautista, diego fernando; alejandro rey, josé; giraldo-ramírez, nelson title: consenso ecmo colombiano para paciente con falla respiratoria grave asociada a covid- date: - - journal: nan doi: . /j.acci. . . sha: doc_id: cord_uid: gbbkcwo antecedentes y objetivos: la epidemia de covid- ha creado un desafío sin precedentes en el sistema de salud, generando una demanda creciente. alrededor del % de los pacientes diagnosticados con esta infección requieren ingreso a cuidados intensivos principalmente para soporte ventilatorio con ventilación mecánica por un síndrome de dificultad respiratoria aguda de moderado a grave. las mortalidades reportadas pueden ser muy altas. los dos principales las causas de muerte en esta infección son la hipoxemia refractaria asociada al sdra y el shock con insuficiencia orgánica múltiple. la oxigenación con membrana extracorpórea (ecmo) se ha utilizado en pacientes con hipoxemia refractaria sin respuesta a manejo con ventilación mecánica protectora, ventilación en posición prono y relajación muscular⁠⁠. la organización mundial de la salud recomienda considerar ecmo en pacientes adultos y pediátricos con covid- y síndrome de dificultad respiratoria aguda (sdra) refractaria, si hay un equipo de expertos disponible. métodos: se utilizó la metodología de consenso formal para generar el consenso ecmo en la infección sars cov- con la mejor evidencia disponible. el desarrollo del consenso combina las técnicas de selección, síntesis, evaluación y gradación de la evidencia: formulación de la pregunta pico, estrategias de búsqueda sistemática y técnicas de síntesis (metaanálisis). la evaluación de la calidad de la evidencia y la graduación de la fuerza de las recomendaciones se realizó con la estrategia grade, generando al final recomendaciones a los tópicos más relevantes del manejo del paciente con covid- candidato a ecmo y por técnica de consenso formal (delphi). resultados: el consenso colombiano para un paciente con falla respiratoria grave asociado a covid- proporciona un resumen de la evidencia sobre el uso de membranas de oxigenación extracorpórea en insuficiencia respiratoria hipoxémica aguda grave asociada con la infección sars cov- , dando recomendaciones sobre sus indicaciones, contraindicaciones, consideraciones y la implementación del grupo ecmored colombia. conclusiones: el consenso colombiano de ecmo es un documento de guía y consulta para el manejo de pacientes con insuficiencia respiratoria aguda grave refractaria y disfunción cardiovascular asociada con covid- candidatos para ecmo. background and objectives: the covid- epidemic has created an unprecedented challenge in the health system, generating increasing demand. about % of diagnosed patients require intensive care admissions primarily for support with mechanical ventilation for a moderate to severe acute respiratory distress syndrome. the reported mortalities can be very high. the two main causes of death in this type of infection are refractory hypoxemia associated to ard and, shock with multiple organ failure. extracorporeal membrane oxygenation (ecmo) has been used in patients with refractory hypoxemia and no response to management with protective ventilation, prone ventilation, and muscle relaxation⁠⁠. the world health organization recommends considering ecmo in adult and pediatric patients with covid- and severe refractory acute respiratory distress syndrome (ards), if an expert team is available. methods: the formal consensus methodology was used to generate the ecmo consensus in the sars cov- infection with the best available evidence. the development of the consensus combined the techniques of selection, synthesis, evaluation and gradation of the evidence: formulation of the pico question, systematic search strategies, synthesis techniques (meta-analysis). the evaluation of the quality of the evidence and the grading of the strength of the recommendations was carried out with the grade strategy. results: the colombian ecmo consensus for a patient with serious respiratory failure associated with covid- provides a summary of the evidence of the use of extracorporeal oxygenation membranes in severe hypoxemic respiratory failure associated with this sars cov- infection, giving recommendations on its indications. contraindications, considerations and the implementation of the ecmored colombia group. conclusions: the colombian ecmo consensus is a consultation and guide document for the management of patients with refractory severe acute respiratory failure and cardiovascular dysfunction associated with covid- candidates for ecmo. covid- es una enfermedad causada por el nuevo virus sars-cov- que apareció en diciembre de y ahora es una pandemia. la epidemia por covid- ha creado un desafío sin precedentes en el sistema de salud, generando una demanda creciente y con frecuencia avasalladora para los hospitales y las unidades de cuidado intensivo. alrededor de un % de los pacientes diagnosticados requieren cuidado intensivo principalmente para soporte con ventilación mecánica por un síndrome de dificultad respiratorioaguda de moderado a grave. las mortalidades reportadas pueden llegar a ser muy altas, en el informe del dr. cumming y col, en pacientes críticos en la ciudad de nueva york, la mortalidad fue del %, pero en pacientes con edad avanzada y comorbilidad cardiaca o pulmonar, además de alteraciones en biomarcadores como il- y dimero d, la mortalidad puede ser mucho mayor ( ). el dr. richardson y col ha reportado mortalidad del % en el grupo de mayores de años ( ) . la mortalidad asociada al síndrome de dificultad respiratoria aguda es explicada por hipoxemia refractaria, choque y falla orgánica múltiple asociada a la hipoxemia. la oxigenación con membrana extracorpórea (ecmo) ha sido utilizado en pacientes con hipoxemia refractaria y ausencia de respuesta al manejo con ventilación protectora, ventilación en posición prono y relajación muscular ( ) . la organización mundial de la salud recomienda considerar ecmo en pacientes adultos y pediátricos con covid- y síndrome de dificultad respiratorio agudo (sdra) severo refractario, si hay un equipo experto disponible ( ) . el uso de ecmo en falla respiratoria refractaria se ha usado en centros especializados y su empleo se incrementó dramáticamente durante la pandemia de influenza a h n de donde se reportaron supervivencias alrededor de % con su implementación ( ) . en medio de esa pandemia, el estudio cesar, mostró que la remisión a un centro de referencia de ecmo se asoció con disminución de la mortalidad ( ) . sin embargo, el estudio tuvo criticas ya que aproximadamente la cuarta parte de los pacientes aleatorizados a ecmo no recibieron esta terapia ( / ), además en el grupo control la adherencia a la ventilación mecánica protectora pudo no ser adecuada ( ) . después de este trabajo, el uso del ecmo ha continuado creciendo en el mundo. durante la epidemia de síndrome respiratorio del medio oriente causado por un tipo de coronavirus (mers-cov) en , fue usado con la misma tasa de éxito ( ) . en el , combes y col publicaron el estudio eolia, un ensayo clínico controlado del uso de ecmo temprano versus terapia convencional incluyendo uso de ecmo de rescate. el estudio fue detenido tempranamente por "futilidad" y no encontró diferencias significativas entre el tratamiento ecmo temprano y el manejo médico convencional. sin embargo, un % de los pacientes del grupo de tratamiento médico convencional requirió ecmo de emergencia por deterioro clínico, teniendo una mortalidad del % versus % cuando el ecmo se iniciaba de manera temprana ( ) . un análisis bayesiano posthoc encontró que era muy probable que el ecmo reduzca la mortalidad en pacientes con sdra severo refractario ( ) . al meta-analizar los estudios cesar y el estudio eolia se encuentra una disminución de la mortalidad a días, con una disminución absoluta del riesgo de muerte de % ( vs %) y un número necesario a tratar (nnt) de , . la reducción relativa de la mortalidad fue % (ic %: %- ) ( ) . es importante mencionar que también se encontró aumento en el número de infecciones y sangrado en el grupo de tratamiento con ecmo ( ) . con base en las estimaciones de epidemias previas que llevan a sdra grave como fue el brote h n en el se calcula un requerimiento de ecmo seria . casos por millón de habitantes ( ); durante la pandemia de mers en el oriente medio, la necesidad de ecmo fue de . % en los pacientes que requirieron ventilación mecánica invasiva ( ) . además, teniendo en cuenta la experiencia inicial en china, donde alrededor del . % de los pacientes con covid- de uci requirieron ecmo ( ) . el grupo ecmo colombia cuenta con el personal, la tecnología y la experiencia para gestionar y dar respuesta a la demanda del servicio de membranas de oxigenación extracorpórea en la nación. el grupo ecmored colombia brinda accesoria y consulta telefónica dirigida de forma central y coordinada con el centro de ecmo de influencia en la región donde se requiera, y de acuerdo a la demanda de esta tecnología, ayuda en la gestión de la remisión al centro ecmo y/o definir como puede llevarse a cabo el mejor proceso para contar con un equipo de transporte en ecmo que pueda ir a la institución donde se encuentra el paciente para iniciar la terapia en la unidad de cuidado intensivo y ser trasladado al centro ecmo más cercano para aquellos pacientes con covid y síndrome de dificultad respiratorio aguda grave refractaria al manejo y/o con choque asociado a disfunción miocárdica. metodología del proceso para generar consenso y realización de la guía ecmo colombia. se utilizó la metodología de consenso formal para generar el consenso ecmo en la infección covid- con la mejor evidencia disponible. el desarrollo del consenso combinó las técnicas de selección, síntesis, evaluación y gradación de la evidencia: formulación pregunta pico, estrategias de búsqueda sistemática, técnicas de síntesis (metanalizar). la evaluación de la calidad de la evidencia y la graduación de la fuerza de las recomendaciones se realizó con la estrategia grade ("grading of recommendations, assessment, development and evaluation"), generando al final recomendaciones a los tópicos más relevantes del manejo del paciente con covid en ecmo, en una siguiente fase fueron sometidas a técnica de consenso formal (delphi), para llegar a un consenso de contexto nacional. las preguntas clínicas relevantes se establecieron por consenso del grupo de expertos en terapia ecmo. las preguntas buscaron responder el papel de la terapia ecmo en la epidemia covid- en colombia, en aspectos relacionados como: antecedentes, la epidemiología esperada; el uso de recurso, manejo optimo y escalonado del sdra y/o falla cardíaca aguda asociada al covid- . ¿cuál es la evidencia de la terapia ecmo?, cual es el momento de considerar remisión para ecmo de acuerdo con el recurso, carga de la enfermedad y tasa de ocupación de la unidad de cuidado intensivo (uci), ¿cuándo iniciar la terapia?, cuando no se debería considerar esta terapia? y cuando considerar desmontar la terapia ecmo por futilidad? se hizo una convocatoria a los grupos de ecmo en colombia a través del líder de cada uno de los grupos y se programó las líneas de trabajo y discusión. en la primera ronda se hizo una discusión global del tema y se establecieron tres grupos de trabajo así: el primero se encargó de los antecedentes de la terapia con ecmo y las experiencias en epidemias pasadas h :n , mers y experiencias actuales con covid- . el segundo grupo se encargó de las indicaciones de la terapia ecmo, contraindicaciones y consideraciones durante la epidemia de acuerdo con el recurso, carga de la enfermedad y requerimiento de uci. el tercero se encargó de las recomendaciones de las sugerencias operativas para contactar el grupo de ecmo, definición de candidato, remisión y rescate in situ. se hizo una formulación de las preguntas con la metodología pico (población, intervención, comparación y resultado final ("outcome")): cada grupo generó entre tres a cinco preguntas, las cuales fueron enviadas al asesor metodológico para evaluación de viabilidad y ajustes. en la segunda ronda se hizo una discusión y se seleccionaron las preguntas a desarrollar en la guía. las preguntas se seleccionaron de acuerdo con la relevancia, viabilidad y grado de acuerdo general. después de la selección de las preguntas, fueron regresadas nuevamente a los subgrupos para que iniciaran el proceso de búsqueda y selección de la evidencia disponible. esta búsqueda sistemática se hizo en las bases de datos pubmed, embase y googlescholar. con el software revman . se hizo el metaanálisis de los estudios susceptibles de sintetizar y se resumió el tamaño del efecto, el riesgo de sesgos se valoró con la herramienta de valoración de estudios individuales de cochrane. j o u r n a l p r e -p r o o f la evaluación de la evidencia de la utilidad del ecmo en el sdra se hizo con el software gradepro-gdt; terminadas estas fases se formularon las recomendaciones específicas. para el tópico de manejo optimo del paciente en ventilación mecánica; la búsqueda encontró metaanálisis que resumía el tamaño del efecto, la calificación de la evidencia y la recomendación se hizo también con el software gradepro-gdt. las demás preguntas se respondieron de acuerdo con la mejor evidencia disponible y los expertos de cada subgrupo fijaron una posición y unas propuestas de recomendación inicial. luego, se hizo discusión general con el grupo completo y el asesor metodológico y se establecieron los postulados finales. los postulados fueron sometidos a la metodología de consenso por el método delphi, con cinco rondas de iteración hasta llegar a un consenso global de aceptación unánime de las recomendaciones. la medición del grado de acuerdo general se evaluó con una escala tipo likert de puntos (en total acuerdo = y en total desacuerdo= ). la consistencia interna de las recomendaciones por cada uno de los expertos se medió con el estadístico alfa de cronbach, el cual reporto un . %. preguntas clínica del consenso ecmo colombia, recomendación y presentación de la evidencia. recomendaciones . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria, con sospecha o confirmación de covid- , debería considerarse la oxigenación con membrana extracorpórea vs continuar con el manejo estándar para disminuir la mortalidad a días? los pacientes con covid- que desarrollen hipoxemia o hipoperfusión refractaria al manejo médico convencional deben ser evaluados por un centro experto en ecmo. la terapia ecmo puede ser considerada de acuerdo con una cuidadosa evaluación del riesgo de muerte del paciente en terapia convencional, la probabilidad de beneficiarse de ecmo y la disponibilidad de recursos humanos y técnicos para aplicar la terapia de manera segura y apropiada. fuerte a favor . ¿en pacientes con síndrome de dificultad respiratoria aguda grave con sospecha o confirmación de covid- , cual es el tratamiento optimo que deben recibir antes de considerar el uso de ecmo? se recomienda que los pacientes con síndrome de dificultad respiratoria aguda moderada a grave, con sospecha o confirmación de covid- , reciban ventilación pulmonar protectora de acuerdo con la estrategia ards-net, sedación profunda y relajación muscular, ventilación prona además de prevención y manejo de la hipervolemia. se pueden considerar las maniobras de reclutamiento pulmonar en pacientes con hipoxemia refractaria como medida transitoria para mejorar la oxigenación; se alerta de sus posibles efectos deletéreos hemodinámicos y riesgo de barotrauma. se sugiere que en paciente con sdra grave con hipoxemia refractaria y donde este el recurso disponible, reciban terapia con óxido nítrico inhalado como medida de estabilización y de prueba, mientras es contactado el grupo de ecmo. punto de buena practica . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , ¿cuáles son las indicaciones del uso de ecmo? el consenso colombiano recomienda la utilización de ecmo con las indicaciones elso en el contexto de covid- , haciendo especial énfasis en la escogencia rigurosa de pacientes y teniendo en cuenta los recursos de cada institución y el nivel de alerta en el momento de la indicación. indicación ecmo vv, en pacientes sin compromiso hemodinámico o disfunción de otro órgano, o en casos de tiempo de ventilación mecánica menor de días -pao /fio < mmhg por hrs -pao /fio < mmhg por hrs--ph < , más paco > mmhg por hrs. con pao /fio > mmhg en pacientes con disfunción orgánica y ventilación mecánica menor a días con ventilación mecánica no protectora o ph < , y paco > mmhg, refractario al manejo. . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , qué pacientes deben considerarse de atención prioritaria para el inicio de la terapia? se sugiere que la consideración de la atención prioritaria para pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , dando prioridad a los pacientes con mayor probabilidad de supervivencia con independencia, autonomía y buena calidad de vida. esta valoración se realiza utilizando la escala resp y la evaluación de la fragilidad. punto de buena practica . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , qué pacientes deben ser excluidos de indicación de terapia ecmo? se sugiere que pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , deben excluirse de la terapia ecmo de acuerdo con la muy baja probabilidad de beneficio con dicha intervención. estos criterios incluyen contraindicaciones absolutas como son un puntaje de fragilidad alto mayor de , falla orgánica múltiple con sofa mayor de , enfermedad neurológica y pobre pronostico neurológico, enfermedad cardiovascular, pulmonar, hepática o renal avanzada y la imposibilidad de implementar la terapia como es la contraindicación para transfusión y la anticoagulación. además, se incluyen una serie de contraindicaciones relativas como son la edad, el índice de masa corporal mayor de , inmunocomprometidos, entre otras (tabla . contraindicaciones relativas y absolutas). punto de buena practica . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , ¿cómo modifica la disponibilidad de recursos, carga de trabajo y porcentaje de ocupación las indicaciones de ecmo? se sugiere que los pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- sean considerados candidatos para terapia con ecmo de acuerdo con la probabilidad de beneficiarse de la terapia y de acuerdo con la disponibilidad de camas de uci. punto de buena practica . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , cuando debería considerarse el desmonte del tratamiento de ecmo por futilidad terapéutica? se sugiere que los pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , a los cuales se les inicio terapia con ecmo, sean reevaluados en forma periódica. este soporte debe ofrecerse como una prueba limitada en el tiempo y ser explicada como tal a todas las partes implicadas desde el principio. las decisiones de futilidad de la terapia deben ser individualizadas basadas en una valoración multidisciplinaria evaluando el contexto clínico, la evolución del paciente y las posibilidades objetivas de recuperación pulmonar y/o cardíaca. otro punto para tener en cuenta es determinar la disponibilidad de los recursos por regiones, considerando en situaciones de alta demanda; se sugiere una reevaluación a los - días para definir la prolongación de la terapia ecmo. además, en casos complejos las decisiones pueden ser consultadas con el comité de ética institucional y también serán discutidas en grupo de consenso nacional de ecmored colombia. punto de buena practica . ¿cómo debe realizarse el proceso de referencia y traslado de los pacientes con indicación de ecmo por covid- en colombia? se sugiere la consolidación de una comisión ecmored colombia conformada por los líderes de los grupos ecmo del país, la cual servirá para estandarizar los procesos de selección de los candidatos y definir el traslado, transporte y derivación al centro de ecmo más cercano con disponibilidad del recurso. además, esta comisión servirá como órgano consultor al gobierno nacional, aseguradoras e instituciones prestadoras de servicios en salud. punto de buena practica . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria, con sospecha o confirmación de covid- , debería considerarse la oxigenación con membrana extracorpórea vs continuar con el manejo estándar para disminuir la mortalidad a días? recomendación fuerte a favor presentación de la evidencia se hace una búsqueda sistemática de la literatura en pubmed, embase y google scholar. se seleccionas los ensayos clínicos controlados y estudios de cohorte con grupo control y revisión de metaanálisis previos. se encontró un metaanálisis del del dr. musichi ( ) , se hace actualización de este con los nuevos artículos publicados. la nueva búsqueda solo encuentra un estudio de cohorte realizado por el dr. se realiza el nuevo análisis ( , , ( ) ( ) ( ) ( ) . el estimador puntual muestra que en pacientes con síndrome de dificultad aguda grave refractaria la terapia con ecmo vs tratamiento estándar se asocia con una disminución relativa de la mortalidad de . (ic %: . a . ) con una heterogeneidad de %. se hace un análisis grafico del posible sesgo de publicación con el "funnel plot", donde no se evidencia en forma gráfica sesgo de publicación. análisis por subgrupos, incluyendo solo los ensayos clínicos controlados (peek et al., )( ) y (combes et al., )( ) muestra una reducción de la mortalidad alrededor del %. estos resultados son similares al beneficio encontrado en el estudio eolia (combes ) cuando se hizo por análisis bayesiano ( ). figura . comparación del efecto de la terapia con ecmo vs tratamiento estándar en pacientes con síndrome de dificultad aguda grave refractaria en la mortalidad a días. tabla tabla de resumen de evidencia y recomendación, software grade pro gdt de la organización cochrane. hay cada vez más evidencia del efecto del ecmo en pacientes con infección por sars cov y sdra grave refractario, algunas de las experiencias han sido en japón (ecmonet-japan, ) ( ) se recomienda que los pacientes con síndrome de dificultad respiratoria aguda moderada a grave, con sospecha o confirmación de covid- , reciban ventilación pulmonar protectora de acuerdo con la estrategia ards-net, sedación profunda y relajación muscular, ventilación prona además de prevención y manejo de la hipervolemia. mientras la ventilación mecánica es una intervención que potencialmente salva vidas, ella puede también empeorar la lesión pulmonar y a través de la lesión asociada al ventilador, en sus componentes de barotrauma, volutrauma, atelectrauma y biotrauma, puede contribuir a la disfunción orgánica múltiple en los pacientes con sdra. entre las estrategias que han mostrado efectividad para disminuir este riesgo y disminuir la mortalidad esta la ventilación mecánica protectora ( ) . una revisión sistemática de la literatura y metaanálisis encontró una asociación entre volumen corrientes altos y la mortalidad. además, en el mismo metaanálisis se demostró que una estrategia ventilatoria con volúmenes corrientes bajo y con peep alto (ensayos clínicos controlados # y , pacientes incluidos) redujo el riesgo relativo de muerte (rr, . , ic %: . a . ) ( ). -el manejo ventilatorio basado en la mejor evidencia disponible es el uso de ventilación mecánica protectora con volumen corriente bajos de (vt) - ml/kg de peso ideal, presión positiva al final de la espiración (peep) manejado de acuerdo a la tabla fio y peep, con este último estando entre - cmh , una presión meseta menor de y una frecuencia respiratoria entre - para un ph superior a . y co menor de ( ) . además, se considera que una estrategia de protección pulmonar adicional es la ventilación con una presión de conducción de la vía aérea (presión de conducción) menor de , y se debería utilizar en la medida de lo posible (amato et al., )( ). -sedación profunda y relajación muscular, cuando con la sedación no se ha logrado el objetivo ventilatorio y de sincronía ( , ) . punto de buena práctica. el consenso colombiano recomienda la utilización de ecmo con las indicaciones elso en el contexto de covid- , haciendo especial énfasis en la escogencia rigurosa de pacientes y teniendo en cuenta los recursos de cada institución y el nivel de alerta en el momento de la indicación. la oms, en su guía para el tratamiento clínico de la infección respiratoria aguda grave, recomienda que se considere el uso del ecmo en pacientes con hipoxemia refractaria con sospecha de covid- y en entornos con acceso a especialistas en ecmo ( ). respecto a recomendaciones específicas la elso sugiere los criterios de inclusión del estudio eolia, el cual determina que el ecmo se debe considerar cuando se cumple uno de los siguientes tres criterios, siempre y cuando se halla optimizado la ventilación mecánica (fio ≥ . , volumen corriente ml/kg peso ideal, peep ≥ mm hg) y tenga una duración menor a siete días y una de las siguientes indicaciones ) pao /fio < mmhg por hrs, ) pao /fio < mmhg por hrs, o ) ph < , más paco > mmhg por hrs. la elso (extracorporeal life support organization) considera que el inicio de la terapia ecmo es una responsabilidad local (hospitalaria y regional). es una decisión caso por caso que debe reevaluarse regularmente en función de la cantidad de pacientes en falla respiratoria, la disponibilidad de personal y otros recursos, así́ como de las políticas gubernamentales, regulatorias u hospitalarias locales (elso, )( ). . ¿en pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , qué pacientes deben considerarse de atención prioritaria para el inicio de la terapia? punto de buena practica se sugiere que la consideración de la atención prioritaria para pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- sea con base en la posibilidad de beneficio con dicha intervención dada por la probabilidad de supervivencia a priori calculada con la escala resp, además de tener en cuenta el índice de fragilidad del paciente y la disponibilidad del recurso de acuerdo con el porcentaje de ocupación de uci. la tarea de priorización no es sencilla, en especial porque no existe aún una regla o puntaje de predicción que evalúe cuales son los factores que ayudan a definir cuál es la probabilidad de supervivencia de un paciente con covid antes de ser conectado a la terapia. en este contexto, es necesario tomar los criterios de estudios previos que evalúan la posibilidad de supervivencia de pacientes con ecmo vv en otras patologías. adicionalmente, existen tres escenarios para definir la prioridad para que un paciente sea considerado para la terapia, uno de ellos es la escala de fragilidad clínica, la cual ya ha sido evaluada previamente para pacientes en cuidados agudos y el segundo punto es la disponibilidad de camas de uci y finalmente la disponibilidad de atención en los centros de ecmo durante la evolución de la pandemia actual. para evaluar la posibilidad de supervivencia, este grupo toma como referencia el puntaje de supervivencia en oxigenación de membrana extracorpórea respiratorio (resp score) (schmidt et al., )( ), el cual valora la posibilidad de supervivencia previo al inicio de la terapia de los pacientes candidatos, clasificando los pacientes en cinco grupos de riesgo de supervivencia hospitalaria, esta herramienta está disponible en línea en la dirección web http://www.respscore.com/. este puntaje no se tomará como un criterio absoluto para definir la indicación o contraindicación de la terapia, su papel es el de priorizar el tratamiento de acuerdo con la evolución de la pandemia también es importante evaluar, cual es la posibilidad que existe de tener malos desenlaces en morbilidad hospitalaria, tiempo de estancia y mortalidad en función de su edad y su estado funcional (juma, taabazuing, & montero-odasso, ) ( ) . para este consenso, uno de los criterios para usar la terapia ecmo es la condición de fragilidad de los pacientes, se considera que el mayor beneficio de ésta se da en pacientes con un puntaje de fragilidad clínica inferior a cuatro. aún es incierto cuál será la magnitud del impacto de la infección por sars cov en los servicios de salud en colombia, pero si el comportamiento es similar al observado en otros países, nosotros estaremos con una baja disponibilidad de camas de hospitalización y de cuidado intensivo, esta perspectiva nos impone una variable adicional para la optimización de recursos tanto a nivel nacional como regional. de acuerdo con este contexto, la asignación de la terapia de ecmo se priorizará tomando como guía los criterios utilizados por el gobierno chileno (ver tabla ) que recoge entre otros la tasa de ocupación de uci, la edad, días de ventilación mecánica y probabilidad de supervivencia (ministerio de salud de chile, )( ). se sugiere que pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , deben excluirse de la terapia ecmo de acuerdo con la muy baja probabilidad de beneficio con dicha intervención. estos criterios incluyen contraindicaciones absolutas como son un puntaje de fragilidad alto mayor de , falla orgánica múltiple con sofa mayor de , enfermedad neurológica y pobre pronostico neurológico, enfermedad cardiovascular, pulmonar, hepática o renal avanzada y la imposibilidad de implementar la terapia como es la contraindicación para transfusión y la anticoagulación. además, se incluyen una serie de contraindicaciones relativas como son la edad, el índice de masa corporal mayor de , inmunocomprometidos, entre otras. presentación de la literatura en la actualidad no existen publicaciones específicas para evaluar cuales son las contraindicaciones para pacientes con covid . en este ámbito, es necesario utilizar las contraindicaciones usuales para pacientes que requiere ecmo con otras indicaciones y con los modelos de predicción para estas patologías ( , , ) . es posible que en situaciones de alta ocupación secundario a la pandemia por la enfermedad por sars-cov y de acuerdo con la evolución de las camas disponibles en el centro de ecmo y a nivel regional/nacional, se cambien los criterios de utilización de ecmo veno-venoso (ecmo vv) y veno-arterial (prekker et al., )( ). se sugiere que los pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- sean considerados candidatos para terapia con ecmo de acuerdo con la probabilidad de beneficiarse de la terapia, la cual comprende escala de supervivencia, edad, días de ventilación mecánica y datos de la mecánica respiratoria, de acuerdo con la disponibilidad de camas de uci (ministerio de salud de chile, ) ( ) . presentación de la literatura. los estados de acuerdo con la carga de la enfermedad y disponibilidad de recursos han planteado unas pautas que incorporan la mayor probabilidad de beneficio con la intervención y al mismo tiempo la disponibilidad de un recurso finito como es la disponibilidad de camas de uci. el consenso ecmo colombia se adhiere a recomendaciones internacionales y toma como base la expresada por la guía recomendación para indicaciones de ecmo durante la pandemia covid- del estado de chile. se sugiere que los pacientes con síndrome de dificultad respiratoria aguda grave refractaria con sospecha o confirmación de covid- , a los cuales se les inicio terapia con ecmo, sean reevaluados en forma periódica. este soporte debe ofrecerse como una prueba limitada en el tiempo y ser explicada como tal a todas las partes implicadas desde el principio. las decisiones de futilidad de la terapia deben ser individualizadas basadas en una valoración multidisciplinaria evaluando el contexto clínico, la evolución del paciente y las posibilidades objetivas de recuperación del pulmonar y/o cardíaca. otro punto para tener en cuenta es determinar la disponibilidad de los recursos por regiones, considerando en situaciones de alta demanda, se sugiere una reevaluación a los - días para definir la prolongación de la terapia ecmo. además, en casos complejos las decisiones pueden ser consultadas con el comité de ética institucional y también serán discutidas en grupo de consenso nacional de ecmored colombia. presentación de la literatura. la evaluación de la eficacia del ecmo en covid- es compleja y sus indicaciones son sometidas a un cambio constante. este soporte debe ofrecerse como una prueba limitada en el tiempo y ser explicada como tal a todas las partes implicadas desde el principio. las decisiones de futilidad de la terapia deben ser individualizadas basadas en una valoración multidisciplinaria evaluando el contexto clínico, la evolución del paciente y las posibilidades objetivas de recuperación del pulmonar y/o cardíaca considerando que los pacientes fueron escogidos en el marco de una selección estricta con mayor posibilidad de supervivencia, basados en modelos predictivos que no tienen en cuenta el covid- como causa del compromiso orgánico ( , ) . los resultados en ecmo en covid- son limitados, hasta el momento la supervivencia es cercana a un % con un promedio de - días , sin embargo, muchos de los pacientes continúan en terapia (jacobs et al., ) ( ) . otro punto a tener en cuenta es determinar la disponibilidad de los recursos por regiones, considerando en situaciones de alta demanda, se sugiere una reevaluación a los - días para definir la prolongación de la terapia ecmo (rajagopal et al., ) ( , ) . es importante enfatizar que todas las decisiones deben estar centradas en el paciente y familia, basadas en una comunicación clara de todos los procesos por parte del grupo tratante con el apoyo del comité de ética de la institución (joebges & biller-andorno, ) ( ) . además, en casos complejos las decisiones pueden ser consultadas y discutidas en grupo de consenso nacional de ecmored. . ¿cómo debe realizarse el proceso de referencia y traslado de los pacientes con indicación de ecmo por covid- en colombia? punto de buena practica se sugiere la consolidación de una comisión ecmored colombia conformada por los líderes de los grupos ecmo del país, la cual servirá para estandarizar los procesos de selección de los candidatos y definir el traslado, transporte y derivación al centro de ecmo más cercano con disponibilidad del recurso. además, esta comisión servirá como órgano consultor al gobierno nacional, aseguradoras e instituciones prestadoras de servicios en salud. la se propone la consolidación de la comisión ecmored colombia, la cual estará conformada por líderes de los grupos de ecmo en el país, con el fin de estandarizar los procesos de selección de pacientes candidatos a la terapia. las decisiones de aceptación o rechazo serán evaluadas por el grupo ecmo institucional al cual sea presentado el paciente, con el apoyo de la comisión para concertación de decisiones en situaciones complejas y/o en caso de requerir ecmo transporte, con el fin de tener claro movimientos de los candidatos entre instituciones que garanticen oportunidad y seguridad para el paciente, con manejo eficiente de los recursos, basados en la capacidad instalada de instituciones prestadoras de salud (ips) para garantizar servicios de ecmo en concordancia con los procesos administrativos de convenios entre ips y empresas promotoras de salud (eps) (decreto / , republica de colombia) (tabla ). en este sentido se propone posterior a la presentación del paciente por central de referencia o médico tratante, que el líder del centro ecmo que recibe la alerta, active a su par experto de la comisión que se encuentre de disponibilidad para realizar un resumen del caso y en diez minutos evaluar si el paciente es candidato o no, y en casos indeterminados ampliar la consulta a dos miembros más de la comisión para tomar la decisión en consenso. si es candidato y no tiene opción de traslado primario, se trasladará el grupo ecmo transporte con mayor cercanía a la ips remisora. la comisión ecmo sugiere crear un programa colaborativo interinstitucional con el fin de direccionar la distribución de los pacientes de acuerdo con la localización geográfica y capacidad instalada (experiencia similar implementada en japón (ecmonet-japan, )( ) y francia (haye, ) ( ) . para las situaciones que requieran transporte, se puede apoyar con los grupos de ecmo móvil (bogotá, bucaramanga, medellín) para realizar traslados de pacientes candidatos a ecmo no solo a la institución que realiza el transporte sino a otras ips que cuenten con el programa de ecmo basados en la información la comisión ecmored colombia. para participar en este convenio se debe tener aval de las directivas donde se cuenta con el programa ecmo transporte para permitir el apoyo interinstitucional. para los casos donde el grupo ecmo transporte no remite al paciente a su ips, se plantean dos formas de facturación de dicha gestión:  tramitar el pago de la gestión operativa directamente con la ips que acepte el paciente por lo cual se consolidarán convenios interinstitucionales para dar trámite al pago definido por la comisión ecmored colombia.  realizar por medio del área de referencia y contra referencia el trámite ante la eps del paciente la autorización de dicha gestión operativa, con los soportes de traslado definido por la institución. en caso de traslados es importante certificar primero las condiciones de seguridad del personal que va a realizar el transporte para reducir el riesgo de contaminación cruzada. si la capacidad del sistema se ve comprometida se hará una selección más rigurosa de los pacientes, dando prioridad a las personas con mayores probabilidades de supervivencia. en casos de saturación del sistema de salud, se reevaluará el beneficio de ecmo en esos momentos. epidemiology, clinical course, and outcomes of critically ill adults with covid- in new york city: a prospective cohort study presenting characteristics, comorbidities, and outcomes among patients hospitalized with covid- in the new york city area 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predicting survival after ecmo for refractory cardiogenic shock: the survival after veno-arterial-ecmo (save)-score the preserve mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome regional planning for extracorporeal membrane oxygenation allocation during covid- advanced pulmonary and cardiac support of covid- patients ethics guidelines on covid- triage-an emerging international consensus covid- outbreak in france: setup and activities of a mobile extra corporeal membrane oxygenation (ecmo) team during the first weeks key: cord- -z rghua authors: sampaio, pedro paulo n.; ferreira, roberto m.; de albuquerque, felipe n.; colafranceschi, alexandre s.; de almeida, alexandre c.p.; nunes, marcos alexandre v.; filho, joão mansur; lima, ricardo antônio c. title: rescue venoarterial extracorporeal membrane oxygenation after cardiac arrest in covid- myopericarditis: a case report date: - - journal: cardiovasc revasc med doi: . /j.carrev. . . sha: doc_id: cord_uid: z rghua coronavirus disease- (covid- ) has been associated with potentially life threatening cardiovascular complications, including fulminant myocarditis and cardiac tamponade. optimal management strategies are still unclear, including the role of immunomodulatory therapies and extracorporeal membrane oxygenation (ecmo) in the context of cardiogenic shock. we report a case of a middle-aged female with covid- who developed respiratory distress and hemodynamic deterioration with elevated troponin levels on the seventh day of symptoms. echocardiography demonstrated pericardial effusion with diastolic restriction of the right ventricle. cardiac arrest developed during pericardiocentesis, resulting in emergency thoracotomy and pericardial drainage. venoarterial ecmo was subsequently initiated due to refractory cardiogenic shock. tocilizumab, immunoglobulin, methylprednisolone and convalescent plasma were added to supportive care, with progressive recovery of cardiac function and successful weaning from mechanical ventilation. this case highlights the potential role of ecmo, convalescent plasma and immunomodulatory therapies in the management of cardiogenic shock associated with covid- myopericarditis. coronavirus disease- (covid- ) has specific clinical characteristics which differentiate the condition from other respiratory viruses, especially regarding cardiovascular and thrombotic complications. cardiac injury can occur in up to % of hospitalized patients and is associated with worse outcomes [ ] . the role of extracorporeal membrane oxygenation (ecmo) in this scenario has yet to be clearly determined, since it has not been available in most healthcare facilities treating patients with covid- around the world. even in larger case series of hospitalized patients ecmo was rarely used, especially venoarterial [ ] . we report a case of covid- myopericarditis complicated by tamponade and cardiac arrest, successfully managed with venoarterial ecmo, convalescent plasma and immunomodulatory therapies. a -year-old female with covid- , confirmed days previously by nasopharyngeal swab testing, presented to the emergency department on may th , following a day progression of dyspnea, fever, myalgia and postural hypotension. the patient had no previous comorbidities and denied any regular medications. on admission, heart rate was bpm, blood pressure / mmhg, respiratory rate breaths/min and oxygen saturation % on room air. thoracic computed tomography confirmed bilateral pulmonary infiltrates compromising less than % of both lungs, in addition to pleural and pericardial effusions ( fig. a and b) . transthoracic echocardiography (tte) demonstrated normal biventricular function, with moderate pericardial effusion and diastolic restriction of the right ventricle ( fig. c and d ). initial troponin i was pg/ml (reference < pg/ml), and the remaining blood tests are shown in table . azithromycin, piperacillin/tazobactam and teicoplanin were initiated before admission to the intensive care unit (icu). j o u r n a l p r e -p r o o f journal pre-proof within hours of icu admission, cardiac tamponade developed, necessitating urgent tte-guided subxiphoid pericardiocentesis. the procedure was unsuccessful and minutes after needle insertion, cardiac arrest in asystole was diagnosed. emergency thoracotomy was performed and followed by internal cardiac compression and pericardial drainage. the pericardial fluid was citrine yellow and no evidence of ventricular laceration was identified. although spontaneous circulation was restored after five minutes, the patient progressed to refractory circulatory shock, despite the administration of noradrenaline, dobutamine, milrinone and vasopressin. new biventricular dysfunction was visualized on tte and peak troponin levels reached , pg/ml. haemodialysis was interrupted on july nd and besides the development of critical illness myopathy, no further complications were identified. discharge from the icu occurred on july th , and was followed by further echocardiographic confirmation of complete biventricular recovery. hospital discharge was given on july th with continuation of physiotherapy and voriconazole for weeks. heart failure has been diagnosed in up to % of patients with covid- , notably as a result of myocarditis, though pericardial involvement and tamponade have also been described [ , ] . while pericardiocentesis may be life-saving, subsequent management of respiratory insufficiency, myocardial dysfunction and circulatory shock can be challenging, since hemodynamic collapse is usually multifactorial [ ] . although circulatory support should be individualized, venoarterial ecmo may be a suitable choice when simultaneous respiratory and myocardial dysfunction are present. managed with ecmo, only were treated with venoarterial support [ ] . as new knowledge continues to evolve in this area, case reports are relevant to provide the foundation for the development of additional research. few cases of fulminant myocarditis have been published in this context, and the benefit of ecmo remains uncertain, especially after recovery from cardiac arrest. only successfully treated cases of covid- fulminant myocarditis and cardiogenic shock have been previously described, of which was treated with venoarterial ecmo. neither utilized tocilizumab or convalescent plasma as a management strategy. in addition, only report of emergency ecmo cannulation after cardiac arrest in a patient with covid- has been formerly documented, despite a subsequent unfavourable outcome [ ] . in selected cases, ecmo may offer a possibility for spontaneous recovery and administration of immunomodulatory and supportive therapies, though the inherent risks associated with the procedure should be appreciated. although patients seem to fare poorly in this scenario, our case is distinctive from previous descriptions because of the successful outcome. selecting the appropriate moment to initiate ecmo is essential to ensure that the management strategy does not inflict a higher risk than the underlying disease. the identification of significant determinants of poor outcomes associated with ecmo support, such as older age, multiorgan failure, systemic comorbidities or severe respiratory compromise, is crucial to aid in clinical decision making in this setting [ ] . in our case, though the post cardiac arrest neurological status was still uncertain, the absence of additional predictors of mortality and the early indication of hemodynamic support provided a favourable scenario for recovery of myocardial function. optimal management of anticoagulation during ecmo support in covid- is unknown, particularly due to the increased thrombotic risk associated with the disease. despite preliminary observational data suggesting higher prophylactic heparin doses in patients with covid- , it is unclear whether increasing ufh anticoagulation levels is associated with improved outcomes during ecmo support. acquired antithrombin deficiency in this scenario can result in both thrombotic and haemorrhagic complications, which results in unpredictable net clinical effects associated with higher anticoagulation doses [ ] . harlequin syndrome could also be a concern, since pulmonary function in patients with covid- may only recover over several weeks. switching to venovenous ecmo or optimizing ventilator parameters before removing circulatory support are potential options. furthermore, management of bleeding, secondary infections, renal failure and neurological complications are crucial components to achieve a successful outcome. we describe the first case of fulminant covid- myopericarditis and tamponade successfully treated with venoarterial ecmo, neutralizing antibodies and anti-inflammatory therapies, after recovery from cardiac arrest. although stunned myocardium might have contributed to the cardiogenic shock, this complication tends to occur after longer periods of cardiac arrest and the subsequent recovery of ventricular function is often sooner than what was observed (< hours) [ ] . supportive measures are still essential in this scenario, since evidence-based interventions are currently lacking. subcutaneously. after adjustment for a series of clinical variables, tocilizumab was associated with a significantly reduced risk of mechanical ventilation or death (adjusted hazard ratio . , % ci . - . ; p= . ), although with a higher incidence of new infections ( % vs %, p< . ) [ ] . though tocilizumab has also been previously used without concomitant plasma therapy or ecmo in a recovered case of covid- myocarditis, randomized trials are still necessary to clarify the exact role of interleukin- inhibitors in this context [ ] . as such, it is difficult to estimate the influence of these interventions on our patient's outcome until additional research has been published. our report illustrates the importance of appropriate supportive measures in fulminant covid- myopericarditis, particularly the potential role of timely venoarterial ecmo support for circulatory shock following recovery from cardiac arrest. clinical risk stratification should be thoroughly performed in these cases to identify patients who may not benefit from the intervention. further studies should also explore the effects of convalescent j o u r n a l p r e -p r o o f figure clinical characteristics of hospitalized patients with novel coronavirus infected pneumonia in wuhan, china covid- and ecmo: the interplay between coagulation and inflammation-a narrative review covid- for the cardiologist cardiac tamponade secondary to covid- extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with covid- : a retrospective cohort study cardiovascular collapse in covid- infection: the role of veno-arterial extracorporeal membrane oxygenation (va-ecmo) reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest effectiveness of convalescent plasma therapy in severe covid- patients investigational covid- convalescent plasma -emergency inds tocilizumab for cytokine storm syndrome in covid- pneumonia: an increased risk for candidemia tocilizumab in patients with severe covid- : a retrospective cohort study a recovered case of covid- myocarditis and ards treated with corticosteroids, tocilizumab, and experimental at- diagnostic and therapeutic procedures were supported by the samaritano hospital, botafogo.the authors declare that there is no conflict of interest.j o u r n a l p r e -p r o o f journal pre-proof key: cord- -kx ew ap authors: riera, jordi; argudo, eduard; martínez-martínez, maría; garcía, sandra; garcía-de-acilu, marina; santafé, manel; díaz, cándido; contreras, sofía; cortina, alexandra; bonilla, camilo; pacheco, andrés; resta, paula; palmer, neiser; castro, miguel Ángel; ferrer, ricard title: extracorporeal membrane oxygenation retrieval in coronavirus disease : a case-series of patients supported at a high-volume extracorporeal membrane oxygenation center date: - - journal: crit care explor doi: . /cce. sha: doc_id: cord_uid: kx ew ap objective: to evaluate the performance of the extracorporeal membrane oxygenation retrieval team at a high-volume extracorporeal membrane oxygenation center during the coronavirus disease pandemic. design: observational study including all adult patients with confirmed infection due to severe acute respiratory syndrome coronavirus- cannulated at other centers and transported on extracorporeal membrane oxygenation to the icu of the vall d’hebron university hospital between march and june . setting: the icu (capacity expanded to during the pandemic) of the vall d’hebron university hospital (a , -bed public university hospital in barcelona), the referral center for extracorporeal respiratory support in catalonia ( . million inhabitants). patients: extracorporeal membrane oxygenation was considered if the pao( )/fio( ) ratio less than mm hg (refractory to prone position) and/or paco( ) greater than mm hg and ph less than . for more than hours, and no contraindications for extracorporeal support were present. interventions: venovenous extracorporeal membrane oxygenation was initiated in the primary center. then, patients were transferred to the icu of the vall d’hebron university hospital where they received support until respiratory improvement. after decannulation, patients were discharged for rehabilitation at the primary center. measurements and main results: nineteen patients with severe acute respiratory syndrome coronavirus- infection and with a mean pao( )/fio( ) ratio of mm hg ( – mm hg) despite prone positioning and a mean paco( ) of mm hg ( – mm hg) were transferred to our center from their primary hospital after cannulation and received venovenous extracorporeal membrane oxygenation support. prior to cannulation, six patients ( . %) presented vascular thrombosis, and nine ( . %) were already receiving anticoagulant therapy. eighteen transfers were carried out with no significant complications. while on extracorporeal membrane oxygenation, thrombotic events were recorded in nine patients ( . %) and hemorrhagic events in ( . %). thirteen patients ( . %) were successfully weaned, and ( . %) were discharged home. conclusions: extracorporeal membrane oxygenation retrieval can rescue young, previously healthy patients with severe coronavirus disease in whom all the conventional respiratory measures have failed. thrombotic and hemorrhagic complications are frequent in this cohort. www.ccejournal.org • volume • e a significant percentage of critically ill patients with the coronavirus disease (covid- ) may develop hypoxemia and/or respiratory acidosis that are refractory to conventional measures including prone positioning. extracorporeal membrane oxygenation (ecmo) in its venovenous configuration has been shown to be effective in improving gas exchange while allowing a reduction in the mechanical power delivered by mechanical ventilation (mv) in the most severe cases of respiratory failure ( ) . the results of the first published reports of the use of ecmo in covid- were discouraging ( ) ( ) ( ) ( ) ( ) ( ) ( ) ; however, in those studies, key specific data about patient selection and specific management directly related with outcomes after ecmo are lacking. further, although the concentration of patients at high-volume ecmo centers has been associated with better outcomes ( ) , there are no published data available regarding the feasibility of ecmo retrieval of patients with covid- . in the present case series, we describe the activity of the ecmo retrieval team at a regional high-volume ecmo reference center during this pandemic period, focusing on the clinical characteristics of the patients, ecmo management, and outcomes. we also provide details of the activations that were requested but finally rejected. a retrospective analysis was performed of the prospectively recorded data of all the adult patients with confirmed infection due to severe acute respiratory syndrome coronavirus- (sars-cov- ) cannulated at other centers and transported on ecmo to the vall d'hebron university hospital (vhuh) between march and june. data from all the other activations of the ecmo retrieval team in this period were also recorded and analyzed. the vhuh is a , -bed public university hospital in barcelona with a -bed icu. the icu capacity was expanded to during the pandemic, and in all, more than critically ill covid- patients were admitted. criteria for ecmo team activation were a ratio of pao to the fio less than mm hg, refractory to prone positioning (defined by a ratio increase of < % after at least hr), and/or a paco greater than mm hg and ph less than . for more than hours. the contraindications for extracorporeal support, together with a brief description of the vhuh ecmo program and its modification during covid- pandemic, are detailed in appendix (supplemental digital content, http://links.lww.com/ccx/a ). a radiological evaluation of the presence of thrombosis was done if clinically apparent, no routine screening was performed. hemorrhagic complications were recorded as so if the patient required more than ml/kg/d of packed rbc or needed other intervention such as surgery or embolization. the vhuh institutional review board issued a waiver for informed consent since only deidentified patient data were used. data were collected prospectively by investigators and stored in the ecmo database. continuous variables are expressed as mean and range and categorical as percentages. no analysis for statistical significance was performed. nineteen patients with covid- were transferred from their primary hospital after cannulation and received respiratory extracorporeal support at the vhuh, all with a venovenous configuration. the characteristics of the population and the respiratory condition prior to ecmo are detailed in table . the main indication was refractory hypoxemia, with a mean pao /fio ratio of mm hg ( - mm hg) despite prone positioning. respiratory acidosis was also common (paco of mm hg [ - mm hg]), and the mechanical power delivered to the respiratory system was high. in cases ( . %), the team had no information about vessel diameter prior vhuh departure due to the impossibility of placing the proned patient in the supine position because of life-threatening respiratory deterioration when mobilized to this position. significant information on cannulation, transport, and ecmo management is summarized in table . prior to cannulation, vascular thrombosis was present in six patients ( . %), and almost half of the cohort ( . %) received anticoagulation. the femorofemoral approach was the most common cannulation strategy ( . %), and a mean drainage diameter of . f ( - f) allowed a mean ecmo flow of l/min despite daily negative fluid balance. ground transport (ambulance) was used in all the services. there were no (or only minor) complications during transport, except in one case in which pulseless electrical activity (pea) was evidenced, resulting in death despite conversion to extracorporeal cardiopulmonary resuscitation. the cardiac rhythm, the stability of hemoglobin and electrolytes the absence of pericardial occupation, and presence of dilated right ventricle in the echocardiography made us hypothesize that the cardiac arrest was secondary to a massive pulmonary thromboembolism. as soon as extracorporeal support was initiated, the mechanical power delivered to the respiratory system was notably decreased (mean inspiratory pressure of . cm h o [ - . cm h o] and respiratory rate of . breaths/min [ - breaths/min]). during ecmo support, a mean of . ( - ) fiberbronchoscopies and . ( - ) ct per patient were performed. four patients ( %) needed continuous renal replacement therapy and three ( . %) extracorporeal cytokine hemoadsorption. all the patients received heparin infusion, with a daily mean of activated clotting time of . seconds ( - . s). despite this, thrombotic events were detected in nine patients ( . %), with six ( . %) being diagnosed of deep venous thrombosis and five ( . %) needing circuit change. hemorrhagic events were identified in patients ( . %), five of them needing surgery or embolization. regarding the site of bleeding, seven patients ( . %) suffered airways and/or lung hemorrhage, three ( . %) cannula-related bleeding, two ( . %) gastrointestinal blood loss, and one ( . %) hematuria. no thrombotic or hemorrhagic complications were directly associated with patient death. by june, . % of the patients had been successfully weaned and discharged to their primary center, . % were still on ecmo, and . % had died despite the support ( table ). at that time, . % of weaned patients were breathing spontaneously, with no respiratory support, and only one patient was still in the process of mv weaning. in all, . % of the patients were discharged home. in the same period, the team received other calls from centers. more hours of prone positioning were suggested in . % of cases and changes in mv variables in . %. ecmo contraindications were found in . %, advanced age being the most common ( . %). other frequent contraindications were long time on mv ( . %), immunosuppression ( . %), and morbid obesity ( . %). this is the largest published report of ecmo retrieval of patients with severe covid- disease. more than two thirds of the patients were successfully weaned, and . % could be discharged home. life-threatening complications may occur during ecmo transport. furthermore, transporting patients with sars-cov- infection is particularly difficult due to the characteristics of the disease and also due to the requirement of operator protection for contagion ( ) . in our series, of ecmo transports occurred with no significant incidents. one patient developed pea during transport, probably due to pulmonary embolism and subsequently died. other difficulties that we encountered included anticoagulation prior to cannulation, previous venous thrombosis, and lack of information on vein diameter due to the impossibility of placing the patient in the supine position, but, in our series, they did not complicate the performance of the technique. only four of patients died on ecmo, a low rate compared with most of the reports in the literature of its use in patients with covid- ( - ). however, those publications report very short series or compilations of small numbers of cases at many different centers. it has been shown that concentrating ecmo cases in highvolume centers markedly improves outcomes ( ) . a recently published experience of patients supported with ecmo in a french high-volume ecmo center reported a . % icu survival at days, similar to our figures ( ) . they also report frequent thrombotic and hemorrhagic events. there are other circumstances that may explain our positive results. first, ecmo allowed a significant decrease in the mechanical power applied to the lungs, which has been shown to be associated with better outcomes in patients with acute respiratory distress syndrome (ards) ( ) . in our series, it was possible to substantially reduce the inspiratory pressure, together with the respiratory rate, after the initiation of extracorporeal support. further, certain diagnostic and therapeutic maneuvers that are life-threatening with mv support alone could be safely performed with ecmo. we performed fiberbronchoscopy with secretion clearance and microbiological surveillance in most patients, in many cases on a daily basis, which helped to improve respiratory evolution and antibiotic therapy titration. ecmo also allowed the in-hospital transport of patients to the ct scan. images helped clinicians to adjust treatment and better evaluate the evolution of the lung disease. thrombotic and hemorrhagic complications in our cohort were frequent. in fact, the circuit had to be changed in five patients. this is to be expected, since covid- has been associated with coagulation disorders that might be exacerbated by the extracorporeal system ( ) . interestingly, these complications did not have a direct impact on mortality: possible reasons for this include the careful vhuh ecmo team training, the centralization of patients in the same unit, the adequate nurse-patient ratio, and the use of updated anticoagulation management protocols. the uncertainties surrounding the evolution of covid- disease and prognosis of these very severe ards patients, together with the association of ecmo with high resource consumption, mean that the decision to indicate the technique is particularly difficult. in fact, we ruled out activations proposed by the ecmo retrieval team during the study period, either on the grounds that the respiratory condition was not sufficiently severe to benefit from the technique or due to the presence of contraindications that made the indication of ecmo futile. the most common reason for ruling out ecmo was advanced age. the exact cut-off point for age is a matter of debate, but sufficient evidence is available to show that mortality in ecmo increases in the older population. the single-center design of this report may be considered as a limitation. however, ecmo management and protocols vary widely between centers. this variability may alter the conclusions obtained regarding the usefulness of the technique in patients with covid- , and in fact, we see this as a weakness of previously published articles which include small numbers of cases from many different centers ( - , , ) . although the sample in this observational study is one of the largest published to date ( patients), it is not large enough to allow any definitive conclusions to be drawn. in spite of this limitation, this study shows that ecmo retrieval by an experienced team can rescue young, previously healthy patients with severe covid- in whom all conventional respiratory measures have failed. thrombotic and hemorrhagic complications are frequent in this cohort. supplemental digital content is available for this article. direct url citations appear in the printed text and are provided in the html and pdf versions of this article on the journal's website (http://journals.lww.com/ccejournal). cesar trial collaboration: efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ards) due to coronavirus disease (covid- ): pooled analysis of early reports prognosis when using extracorporeal membrane oxygenation (ecmo) for critically ill covid- patients in china: a retrospective case series extracorporeal membrane oxygenation for coronavirus disease clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a singlecentered, retrospective, observational study clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease pneumonia in wuhan, china out-of-center initiation of venovenous extracorporeal membrane oxygenation in covid- patients association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality. analysis of the extracorporeal life support organization registry extracorporeal membrane oxygenation for critically ill patients with covid- -related acute respiratory distress syndrome: worth the effort? prove network investigators: mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts covid- and ecmo: the interplay between coagulation and inflammation-a narrative review extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in coronavirus disease : experience with patients extracorporeal membrane oxygenation for coronavirus disease -induced acute respiratory distress syndrome: a multicenter descriptive study the authors have disclosed that they do not have any potential conflicts of interest.for information regarding this article, e-mail: jorriera@vhebron.net/@jrdelbrio orcid id: https://orcid.org/ - - - (dr. riera). key: cord- -cmtsu g authors: lee, sung woo; yu, mi-yeon; lee, hajeong; ahn, shin young; kim, sejoong; chin, ho jun; na, ki young title: risk factors for acute kidney injury and in-hospital mortality in patients receiving extracorporeal membrane oxygenation date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: cmtsu g background and objectives: although acute kidney injury (aki) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ecmo), few studies have been conducted on the risk factors of aki. we performed this study to identify the risk factors of aki associated with in-hospital mortality. methods: data from adult patients receiving ecmo were analyzed. aki and its stages were defined according to kidney disease improving global outcomes (kdigo) classifications. variables within h before ecmo insertion were collected and analyzed for the associations with aki and in-hospital mortality. results: stage aki was associated with in-hospital mortality, with a hazard ratio (hr) ( % ci) of . ( . – . ) compared to non-aki (p = . ). the simplified acute physiology score (saps ) and serum sodium level were also associated with in-hospital mortality, with hrs of . ( . – . ) per score increase (p = . ) and . ( . – . ) per mmol/l increase (p = . ). the initial pump speed of ecmo was significantly related to in-hospital mortality with a hr of . ( . – . ) per , rpm increase (p = . ). the pump speed was also associated with aki (p = . ) and stage aki (p = . ) with ors ( % ci) of . ( . – . ) and . ( . – . ), respectively. we also found that the red cell distribution width (rdw) above . % was significantly related to stage aki. conclusion: the initial pump speed of ecmo was a significant risk factor of in-hospital mortality and aki in patients receiving ecmo. the rdw was a risk factor of stage aki. the initial pump speed of ecmo was a significant risk factor of in-hospital mortality and aki in patients receiving ecmo. the rdw was a risk factor of stage aki. receiving continuous renal replacement therapy when ecmo were initiated (n = ), if they initiated continuous renal replacement therapy on the date of ecmo insertion (n = ). therefore, patients were ultimately analyzed in the present study. the physiologic and laboratory data within h before ecmo initiation were collected retrospectively through a review of the electronic medical records. the clinical parameters that were recorded included the following: age, sex, causes of admission; causes of ecmo support, mode of ecmo, whether to perform cardiopulmonary resuscitation within h, use of an intra-aortic balloon pump (iabp), ecmo settings, duration of ecmo, urine output, and ventilator settings. initial blood findings, including blood urea nitrogen (bun), total bilirubin, albumin, white blood cells, hemoglobin level, platelet number, red cell distribution width (rdw), sodium, potassium, chloride, and c-reactive protein (crp) were measured. for the severity index, we used the simplified acute physiology score (saps ) [ ] . to calculate the saps , the worst values during the first h before ecmo initiation were used. aki and the stage of its severity were defined according to the guidelines proposed by kdigo [ ] . aki was defined in a case with either an increase in serum creatinine by . μmol/l or . times the baseline within h. the changes in serum creatinine according to the aki stages were as follows: stage , an increase of more than or equal to . μmol/l or an increase to more than or equal to . -to -fold of the baseline; stage , an increase to more than -to -fold of the baseline; stage , an increase to more than -fold of the baseline or more than or equal to . μmol/l with an acute increase of at least . μmol/ l or on renal replacement therapy. the maximum aki stage reached during ecmo support was used to define the incidence of aki [ ] . in-hospital mortality was determined whether a death certificate had been issued or not at d after ecmo insertion. the applied ecmo console was composed of a centrifugal pump and membrane oxygenator. the products utilized included capiox ebs (terumo corporation, tokyo, japan) and quadrox pls (maquet, hirrlingen, germany). the values were expressed as the mean ± standard deviation in continuous variables and n (%) in categorical variables. for the severely skewed variables, such as follow-up duration, the median (interquartile range, iqr) was used. the difference was analyzed by an independent ttest in continuous variables and chi-square test in categorical variables. for the estimated survival, the kaplan-meier method was employed, and the statistical significance was calculated using the log-rank test. for multivariate analysis, logistic regression analysis for aki and coxproportional hazard analysis for in-hospital mortality were carried out. the variables in the multivariate analysis were chosen by p < . in the univariate analysis. calibration was done using the hosmer-lemeshow goodness-of-fit test to compare the numbers of predicted and observed in-hospital mortality and aki. discrimination was analyzed using auroc. the best threshold was calculated by obtaining the best youden index (sensitivity + specificity- ). we consider p < . to be statistically significant. all of the analyses were performed using the spss statistics software (version , ibm, usa). the mean age of the study participants was . ± . years and ( . %) of the participants were male. the reasons for admission were cardiovascular disease ( , . %), lung disease ( , . %), malignancy ( , . %) and others ( , . %). one hundred and thirty seven ( . %) patients had received cardiopulmonary resuscitation within h prior to ecmo initiation. after the median (iqr) ( - ) days of admission, the patients received ecmo insertion because of cardiotomy ( , . %), non-operative cardiovascular causes ( , . %), adult respiratory distress syndrome (ards) ( , . %), non-ards lung causes ( , . %) and other causes ( , . %) . two hundred and thirty ( . %) and ( . %) patients received va and vv ecmo support, respectively. one hundred and six ( . %) patients were undergoing iabp on the date of ecmo insertion. the median (iqr) duration from ecmo initiation to death or discharge was days. the incidence of aki comprising all kdigo grades was . %. in-hospital mortality was . %. the median (iqr) durations for aki and in-hospital mortality were ( - ) days and ( - ) days, respectively. we explored the factors associated with in-hospital mortality. aki developed less frequently in the survivor group than in the non-survivor group. moreover, stage aki developed significantly less in the survivors than in the non-survivors. saps and the serum sodium level were significantly lower in the survivors than in the non-survivors. ventilator settings, such as positive end expiratory pressure and peak inspiratory pressure before ecmo insertion, did not affect the survival rate. the ecmo pump speed was significantly lower in the survivors than in the non-survivors. age, causes of admission, causes of ecmo support, mode of ecmo, use of iabp, length of stay before ecmo insertion, duration of ecmo support, initial urine output, bun, creatinine, rdw and crp were associated with in-hospital mortality ( table ) . we performed a multivariate cox-proportional hazard regression analysis to adjust confounding effects among the selected variables. compared to the non-aki group, the stage aki group significantly increased the risk of in-hospital mortality whereas the stage and aki groups did not (table ). in the kaplan-meier survival curves according to the stages of aki, the estimated mean ( % ci) survival in the non-aki group and the stage , , and groups were . ( . - . ) days, . ( . - . ) days, . ( . - . ) days and . ( . - . ) days, respectively (p < . by log-rank test). in the post-hoc analysis, the stage aki group, but not the stage (p = . ) or (p = . ) aki groups, showed a significant difference in survival compared with the non-aki group (fig ) . with every increment in saps , serum sodium level, and ecmo pump speed ( score in saps , mmol/l in serum sodium level, and , rpm in ecmo pump speed), the risks of in-hospital mortality were increased, with hrs ( % ci, p-value) of . ( . - . , . ), . ( . - . , . ) and . ( . - . , . ), respectively ( table ) . we performed a calibration and discrimination analysis of saps , serum sodium level, and ecmo pump speed to predict in-hospital mortality. all three variables were well-calibrated. the auroc analysis showed the discriminative power of these variables. the cut-off values of saps , serum sodium level, and ecmo pump speed for in-hospital mortality were a score of . , . mmol/l, and . x rpm, respectively (table ) . we compared clinical characteristics according to the mode of ecmo. the length of the hospital stay before ecmo insertion was shorter in patients with va mode than in those with vv mode. the level of crp was lower in the va mode group than in the vv mode group. nonetheless, saps was not different between the two groups. the initial ecmo settings were also comparable between the two groups. according to the linear regression analysis, there was no correlation between saps and ecmo speed either in vv mode (r = . , p = . ) or va mode (r = . , p = . ). the mortality within weeks after ecmo insertion was significantly higher in patients with va mode than in those with vv mode (p = . ), whereas the overall in-hospital mortality was significantly lower in the va mode group than that in the vv mode group (p = . ). compared to the patients with the vv mode, those with the va mode had shorter stays in the intensive care unit and hospital; however, there was no difference in the occurrence of aki between the two groups (table ). because aki, especially stage aki, showed a significant association with in-hospital mortality, we attempted to detect the risk factors associated with aki and stage aki. we compared the characteristics between the patients with and without aki. the initial ecmo pump (table ) . these variables were also significant risk factors for developing stage aki (table ) . there was an additional risk factor in stage aki. the rdw was significantly lower in those without stage aki than in those with stage aki. in the multivariate logistic regression analysis, the rdw was still statistically significant, with an or ( % ci, p-value) of . ( . - . , . ) for every % increase (table ). in the calibration and discrimination analysis, stage aki was well-calibrated and discriminated by a cut-off value of . % for rdw (table ) . we compared patient characteristics according to the rdw status. patients with an rdw above . % showed significantly higher level of crp than did those with an rdw below . %. moreover, patients with an rdw above . % showed considerably lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration than did those with an rdw below . % (table ) . in this work, we investigated the risk factors of aki and in-hospital mortality in patients receiving ecmo support. here, we found that the initial pump speed of ecmo was associated with in-hospital mortality and aki. the elevated rdw could be suggested as the risk factor for severe aki in these patients. this was the first study to identify the risk factors of aki in adult patients receiving ecmo support. because aki is the most common complication and a major risk factor of mortality, defining the risk factors for aki in these patients is extremely important [ ] [ ] [ ] [ ] [ ] [ ] . this study is the largest ecmo assessment ever reported. moreover, the association of pump speed with aki and mortality is a novel finding. we showed that aki, especially stage aki, was a significant risk factor for in-hospital mortality in patients receiving ecmo support. saps and serum sodium level were also important risk factors of in-hospital mortality. along with these well-known and expected findings [ ] [ ] [ ] [ ] [ ] [ ] , we found that the initial pump speed of ecmo was significantly related to in-hospital mortality, with a % increased risk for every , rpm increase. the initial pump speed of ecmo was also a risk factor for both aki and stage aki. on the other hand, the blood flow rate of ecmo was not associated with in-hospital mortality or aki. why a high pump speed, but not a high blood flow rate of ecmo, increases the risk of in-hospital mortality and aki is not clear at this time. however, the ecmo pump can induce hemolysis, leukocyte and platelet destruction, and complement activation [ , ] . blood flow through the ecmo circuit is driven by centrifugal pump. a rotating impeller in centrifugal pumps spins, which creates a constrained vortex that suctions blood into the pump and propels it out toward the membrane oxygenator [ ] . hemolysis has been reported to be associated with aki [ ] . in addition, lou et al. found that the pump speed was a risk factor for hemolysis and that hemolysis was associated with adverse outcomes in pediatric patients receiving ecmo [ ] . although we did not evaluate the degree of hemolysis in our patients, we postulate that hemolysis caused by high revolutions of the ecmo pump might result in aki and in-hospital mortality. to provide stable cardiac output in the va mode and adequate oxygenation in the vv mode, adequate blood flow should be maintained. therefore, clinicians raise the ecmo pump speed as much as possible to maintain adequate blood flow. the blood flow rate that was applied to % of our patients was less than . l/min. a high blood flow extracorporeal circuit that pumped up to l/min [ ] did not apply to our patients; however, . % ( / ) of our patients were treated with a pump speed higher than the cut-off value of . x rpm. for these reasons, we speculate that pump speed, but not a blood flow, is a predictor of death in this study. we compared the clinical characteristics of patients from the va and vv ecmo modes. patients with the vv mode had higher levels of crp, showed higher mortality, and had longer stays in the hospital compared with those with the va mode; however, the mortality within weeks after ecmo insertion was higher in patients with the va mode. we speculated that the patients with the va mode deteriorated rapidly but recovered soon if they were not severe enough for death. in contrast, patients with the vv mode seemed to show slower but poorer outcomes than those with the va mode. the different disease process of the patients treated with the va and vv ecmo modes [ ] might be related to these findings. future prospective studies will be needed to investigate whether ecmo mode determines outcomes. in this study, the higher the rdw was, the more frequently stage aki occurred. to the best of our knowledge, this is the first study to suggest a potential role of the rdw in aki. recently, the use of the rdw as a simple and inexpensive biomarker to predict mortality in chronic heart failure [ , ] , liver disease [ ] , and critical illness [ ] has increased. moreover, the rdw has been reported to be associated with many pathological conditions such as colon cancer, inflammatory bowel disease, celiac disease, rheumatoid arthritis, alzheimer's disease, and contrast-induced nephropathy [ , ] . although the exact mechanism of this relationship is not clear, inflammation is a proposed underlying factor [ , ] . this proposed factor can also be supported by our data, which indicate that the elevated rdw was associated with high crp levels in the patients. in this study, patients with an rdw greater than . % showed lower rbc indices than did those with an rdw less than . %. because anemia is a risk factor for aki [ ] , the low rbc indices found in the elevated rdw group might contribute to increase the odds of stage aki occurring. the current study suffered from several limitations. first, this study is a retrospective cohort study; however, the variables before ecmo insertion were well retrieved with a less than % missing rate. moreover, this is the largest study to explore the association of aki and mortality in patients receiving ecmo support [ ] [ ] [ ] . a low level of missing data and a large number of patients could partially compensate for the weakness of the study design. second, we classified the patients into their kdigo stage based only on their serum creatinine concentration. urine volume is a sensitive marker for the early detection of aki in patients on ecmo. decreased urine volume during ecmo treatment and/or on the day of ecmo removal can be attributed to decreased cardiac output following decannulation, and can be correlated with acute cardiorenal syndrome type [ , , ] . third, we could not provide direct evidence that hemolysis due to a high pump speed resulted in aki in this study. we should have measured plasma-free hemoglobin, which is an indicator of hemolysis. furthermore, we did not obtain information on the cannulation site and mean venous pressure in the ecmo circuit. finally, this study was composed of data from two centers, which could limit the generalizability. in conclusion, aki is a significant risk factor for in-hospital mortality in patients receiving ecmo support. the initial pump speed of ecmo is associated with in-hospital mortality and strongly related to aki, especially stage aki. therefore, once adequate blood flow is maintained, clinicians must be careful not to further increase the ecmo pump speed. because the elevated rdw was also strongly related to stage aki, special attention should be paid to patients with abnormal rdw values to prevent aki. extracorporeal membrane oxygenation in severe acute respiratory failure. a randomized prospective study low-frequency positivepressure ventilation with extracorporeal co removal in severe acute respiratory failure randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal co removal for adult respiratory distress syndrome. american journal of respiratory and critical care medicine extracorporeal membrane oxygenation for ards in adults veno-venous ecmo: a synopsis of nine key potential challenges, considerations, and controversies. bmc anesthesiology referral to an extracorporeal membrane oxygenation center and mortality among patients with severe efficacy and economic assessment of conventional ventilatory 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coronary artery disease validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. archives of pathology & laboratory medicine is anemia at hospital admission associated with in-hospital acute kidney injury occurrence? nephron clinical practice prognosis of patients on extracorporeal membrane oxygenation: the impact of acute kidney injury on mortality predictors of mortality in patients successfully weaned from extracorporeal membrane oxygenation key: cord- -e fesl authors: loforte, antonio; dal checco, erika; gliozzi, gregorio; benedetto, maria; cavalli, giulio giovanni; mariani, carlo; piccone, giulia; agulli, marta; pacini, davide; baiocchi, massimo title: veno-venous extracorporeal membrane oxygenation support in covid- respiratory distress syndrome: initial experience date: - - journal: asaio j doi: . /mat. sha: doc_id: cord_uid: e fesl sars-cov- may cause severe respiratory failure due to massive alveolar damage. currently, no adequate curative therapy for coronavirus disease (covid- ) disease exists. by considering overall impact of covid- pandemic outbreak, an increased need of extracorporeal membrane oxygenation (ecmo) support becomes evident. we report on our preliminary institutional experience with covid- patients receiving venovenous ecmo support. coronavirus disease infection was confirmed by usage of polymerase chain reaction tests on either nasopharyngeal or lower respiratory tract swab samples ordered at intensive care unit (icu) admission. consideration of ecmo was based on the presence of severe respiratory failure (murray score > . or ph < . under protective ventilation , - ) with sustained clinical deterioration despite optimal conventional treatment and refractory prone positioning. this has been in accordance with extracorporeal life support organization (elso) guidelines document for the adult patient with covid- . , [ ] [ ] [ ] diffuse bilateral lung injury by sars-cov- was confirmed by chest x-ray or computed tomography (ct) scan in all patients [ ] [ ] [ ] (figure ). aggressive mechanical ventilation (peak or plateau airway pressure > cm h o or fraction of inspired oxygen [fio ] > . ) for more than days, uncontrolled active bleeding, severe comorbidity, multiple organ failure, sepsis, disseminated intravascular coagulation, age > years, and neurologic damage were used as contraindications for vv ecmo institution. , , patients have been considered for ecmo by a multidisciplinary team consisting of experts from anesthesiology and intensive care, cardiac surgery, cardiology, and infectious diseases. the study has been approved by our institutional review board. informed consent was not required for ecmo treatment, as the use of mechanical support was considered a rescue therapy in all patients. the ultracompact cardiohelp (getinge, maquet-cardiopulmonary ag, rastatt, germany) has been adopted as ecmo system. for inflow, the right femoral vein was cannulated percutaneously using the seldinger technique with a cm long, - fr heparin-coated cannula (bio-medicus nextgen, medtronic inc., minneapolis, mn). for reinfusion (outflow), a cm long, - fr heparin-coated cannula (bio-medicus nextgen, medtronic inc.) was used, implanted into the right internal jugular vein. all the components of the ecmo system and tubings were heparin coated (bioline coating; getinge, maquet-cardiopulmonary ag), and systemic anticoagulation was maintained using unfractionated heparin to a partial thromboplastin time of . normal. , , pressures on the ecmo circuit, blood gas analysis, general laboratories, and complete blood coagulation study were also monitored daily. echocardiography was not performed routinely. after cannulation, patient management was optimized to minimize further ventilator-induced lung injury (vili). , [ ] [ ] [ ] regarding oxygenation, ecmo blood flow was maximized to reduce the fio less than . and maintain hemoglobin veno-venous extracorporeal membrane oxygenation support in covid- respiratory distress syndrome: initial experience saturation more than %. positive end-expiratory pressure (peep) was maintained above cm h o. if severe hypoxemia (pao , < mm hg) still subsisted, the threshold for red blood cell transfusion was elevated from . to . g/dl. the threshold for prophylactic platelet transfusion was . /μl, whereas the targeted post-transfusion goal was , /μl in the presence of active bleeding. regarding co removal, sweep gas flow was maximized to allow a normal ph, small tidal volumes (< ml/kg/predicted body weight), and plateau pressures less than cm h o. paralysis and sedation were maintained. after improvement of native lung function (fio < . , peep < cm h o, peak inspiratory pressure in pressure-controlled ventilation [pip] < cm h o), ecmo flow was gradually reduced to . l/min. , - sweep gas flow was then tapered and finally shut off for minutes. if blood gases remained stable for more than hours, the ecmo system was removed, and decannulation was carried out. variables are reported as median and interquartile ranges. for statistical analysis, we used spss . (spss, inc., chicago, il). as of march , , during covid- pandemic outbreak, consecutive adult patients with confirmed infection were admitted at our cardio-thorac-vascular department (out of > confirmed cases throughout s. orsola university hospital, bologna; tables , ). all patients suffered severe respiratory failure and were admitted to our icu. four of them were referred for ecmo establishment ( table ). our ecmo population had no severe comorbidities. the clinical course consisted of rapid in-hospital deterioration with early icu admission for ventilatory support. the murray score , - was used to evaluate respiratory failure severity before vv ecmo implantation. in all patients, alternative rescue therapies such as prone position and inhaled nitric oxide (no) were used before ecmo referral. intensive care unit survival has been % ( table ) . three patients were weaned from vv ecmo ( %). computed tomography scan and chest x-ray typical ground-glass features and consolidations decreased (figure ) . however, the first weaned patient suffered acute recurrence of pneumonia and eventually died on day after vv ecmo removal. the second weaned patient has been successfully extubated and fully mobilized thus joining a rehabilitation care. the third weaned patient is still intubated and on inhaled no with a slight resolution of the pulmonary disease. the remaining patient suffered severe gastrointestinal bleeding, while on ecmo, with high transfusion requirements, namely, of red blood cells (rbc/day . [ . - . ]) and platelets (plt/ day . [ . - . ]), which resulted to be fatal ( table ) . bmi, body mass index; bsa, body surface area; bun, blood urea nitrogen; cpr, c-reactive protein; ct, computed tomography; dbp, diastolic blood pressure; fio , fraction of inspired oxygen; gfr, glomerular filtration; hct, hematocrit; hr, heart rate; il, interleukin; ldh, lactate dehydrogenase; lvef, left ventricular ejection fraction; pbw, predicted body weight; paco , partial pressure of carbon dioxide in arterial blood; pao , partial pressure of oxygen in arterial blood; pct, procalcitonin; peep, positive end-expiratory pressure; plt, platelets; sao , arterial oxygen saturation; sbp, systolic blood pressure; wbc, white blood cells. neither oxygenator failure nor ecmo circuit failure occurred. no neurologic complications occurred. in all patients, lung-protective ventilation was sustained during ecmo support and maintained in the three weaned patients on the first day after ecmo cessation. the level of peep was gradually decreased during weaning from ecmo and afterward during weaning from mechanical ventilation. percutaneous tracheostomy was performed in three patients. all patients received tocilizumab and hydroxychloroquine ( table ) . , lopinavir/ritonavir antiviral therapy was used in two patients. piperacillin/tazobactam antibiotic prophylaxis was used in all patients while azithromycin was adopted, additionally, in one. , , corticosteroids were used in a single case while on ecmo. low dosage of vasoactive drugs (norepinephrine) infusion and consecutive positive fluid balance was frequently needed during vv ecmo support (table ) . , , low dosage of corticosteroids have been used as anti-inflammatory agents after ecmo removal. sars-cov- may cause severe respiratory failure due to massive alveolar damage. [ ] [ ] [ ] [ ] [ ] [ ] the rate of ards ranges from % to % among patients who require hospitalization. , , currently, no adequate curative therapy for covid- disease exists. [ ] [ ] [ ] [ ] [ ] by considering overall impact of covid- pandemic outbreak, an increased need of ecmo support becomes evident. , - so far, the elso registry accounts covid- respiratory ecmo running systems worldwide, mostly being in europe and the united states. , as of april , , euro covid- survey/study showed ongoing vv ecmo patients while have been successfully weaned from ecmo support. , in covid- patients, the initial pulmonary pattern is not similar to ards, as hypoxia is prevalent and pulmonary compliance is generally high. [ ] [ ] [ ] [ ] [ ] the main finding is hypoxic vasoconstriction. the lungs are inflated and increasing peep or prone positioning does not help. lung ct scans in those patients confirm that there are no significant areas to recruit. moreover, high peep levels may compromise right cardiac filling and an increase of the need for fluid intake and/or norepinephrine. [ ] [ ] [ ] ventilator-induced lung injury, volutrauma, barotrauma, oxygen toxicity should be avoided and "lung-protective ventilation" is the recommended strategy for covid- patients. , [ ] [ ] [ ] in addition to viral pneumonia, consequently, those patients likely have had self-inflicted vili, due to diffusely initial type icus management and misunderstanding with subsequent decrease in compliance and edema in the lower lobes. - those patients present a pattern similar to ards and they benefit from peep and prone positioning. if the conservative treatment is not effective, vv ecmo support might be considered. , - unfortunately, ecmo infrastructures and resources are limited, globally. , our small sample of covid- ecmo patients presented young age and showed no severe comorbidities but severe ards occurred in all of them. thus, warm caution and thoughtful approaches for timely detection and treatment should be taken for people who are currently living in high-density covid- -infected areas to preserve life. who: rolling updates on coronavirus disease (covid- elso: covid- cases on ecmo in the elso registry early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia clinical characteristics of covid- in china. reply risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease pneumonia in wuhan, china clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study turkish society of cardiovascular surgery (tscvs) proposal for use of ecmo in respiratory and circulatory failure in covid- pandemic era planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases key: cord- -skr m y authors: slaughter, mark s. title: covid- update date: - - journal: asaio j doi: . /mat. sha: doc_id: cord_uid: skr m y nan the covid- pandemic has resulted in challenges rarely if ever seen before. not only are health care teams struggling to treat a viral illness with potentially devastating and lethal pulmonary complications but having to do so with limited resources and limited treatment options. in those patients with the most severe pulmonary injury, many centers have placed patients on extracorporeal membrane oxygenation (ecmo) hoping that it will support these patients while allowing the lungs to heal. historically, asaio has been a leader as a society in the dissemination of information on ecmo from its annual meeting and journal. thus, we feel obligated to continue to lead by publishing useful, timely and the most up-todate information regarding the use of ecmo and other forms of mechanical support in this patient population. together with our publisher, we have established a rapid publication process so that we can get the latest information online and available to our society members and the larger medical community treating this patient population. after initial online publication, these early clinical experiences and information from elso will be published in an upcoming print issue in a special section dedicated to the treatment of covid- . our first two publications will hopefully help current ecmo programs and centers that might need to transfer patients for more advanced care. li et al. from shanghai, china describe their initial experience treating covid- patients that required ecmo. they give a detailed description of how their program is set up, patients managed, and suggestions for resource utilization. not unexpectedly, the mortality is high, and the duration of support is long in those patients who were able to be weaned from ecmo. the second publication is from elso outlining their initial guidance document for using ecmo in covid- patients with severe cardiopulmonary failure. in an effort to get this information available as soon as possible, the document is also available on their website. the goal of publishing the guidance document as well is to get it in print and serve as a possible resource for the larger community that will be treating these patients. the other goal for this guidance document is that it can and will be updated as we gain clinical experience and start to identify what could be the best medical practice given the data at any given time. we encourage all asaio members that are part of an active ecmo program to submit their cases as they occur to the elso registry. these are tough times, but i am convinced by witnessing the work and dedication of the health care providers not only in my own hospital but in hospitals worldwide, that we are up to the challenge and will succeed. the asaio journal is committed to providing the most up to date information to help these health care teams stay safe and deliver the best care possible. extracorporeal membrane oxygenation for coronavirus disease in shanghai china initial elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure key: cord- -a as bx authors: combes, alain; schmidt, matthieu; hodgson, carol l.; fan, eddy; ferguson, niall d.; fraser, john f.; jaber, samir; pesenti, antonio; ranieri, marco; rowan, kathryn; shekar, kiran; slutsky, arthur s.; brodie, daniel title: extracorporeal life support for adults with acute respiratory distress syndrome date: - - journal: intensive care med doi: . /s - - - sha: doc_id: cord_uid: a as bx extracorporeal life support (ecls) can support gas exchange in patients with the acute respiratory distress syndrome (ards). during ecls, venous blood is drained from a central vein via a cannula, pumped through a semipermeable membrane that permits diffusion of oxygen and carbon dioxide, and returned via a cannula to a central vein. two related forms of ecls are used. venovenous extracorporeal membrane oxygenation (ecmo), which uses high blood flow rates to both oxygenate the blood and remove carbon dioxide, may be considered in patients with severe ards whose oxygenation or ventilation cannot be maintained adequately with best practice conventional mechanical ventilation and adjunctive therapies, including prone positioning. extracorporeal carbon dioxide removal (ecco( )r) uses lower blood flow rates through smaller cannulae and provides substantial co( ) elimination (~ – % of total co( ) production), albeit with marginal improvement in oxygenation. the rationale for using ecco( )r in ards is to facilitate lung-protective ventilation by allowing a reduction of tidal volume, respiratory rate, plateau pressure, driving pressure and mechanical power delivered by the mechanical ventilator. this narrative review summarizes physiological concepts related to ecls, as well as the rationale and evidence supporting ecmo and ecco( )r for the treatment of ards. it also reviews complications, limitations, and the ethical dilemmas that can arise in treating patients with ecls. finally, it discusses future key research questions and challenges for this technology. in a prospective international study conducted in icus across countries, acute respiratory distress syndrome (ards) represented . % of total intensive care unit (icu) admissions [ ] . over the past two decades, inhospital mortality from ards has remained very high at approximately % [ ] . despite strong experimental and clinical evidence [ ] that lung protection improves outcomes in ards, it remains underutilized [ ] . with the ultimate goal of protecting the injured lung, and improving oxygenation, there has been increasing adoption of extracorporeal life support (ecls) in adult patients with very severe ards. advances in supportive care, innovations in technologies and insights from recent clinical trials have contributed to improved outcomes and a renewed interest in the scope and use of ecls [ ] [ ] [ ] . this narrative review provides a summary of some physiological concepts related to ecls, as well as the rationale and evidence supporting the two main forms of ecls for the treatment of ards: extracorporeal membrane oxygenation (ecmo) and extracorporeal co removal (ecco r). we also highlight evidence on complications, limitations, and the ethical dilemmas that can arise in treating patients with ecls. finally, we discuss future key research questions and challenges for this technology. membrane oxygenators are artificial "organs" designed to replace the lungs' gas exchange function by supplying oxygen and removing carbon dioxide (co ) from blood. full-flow venovenous ecmo (vv-ecmo), bicaval dual-lumen jugular vv-ecmo, and ecco r are modalities of ecls for severe ards (fig. ) . during full-flow vv-ecmo venous blood is typically withdrawn from the inferior vena cava through the femoral vein, and then reinjected into the jugular vein (v f -v j ecmo) or the contralateral femoral vein (v f -v f ecmo) after passing through the membrane oxygenator [ ] . the high blood flow (commonly - l/min) and diffusion of gases between blood and the "sweep gas" flowing through the membrane lung's fibers provide oxygen and remove carbon dioxide directly from blood, hence allowing lower intensity mechanical ventilation. bicaval, dual-lumen jugular vv-ecmo was initially considered promising given the single jugular cannulation. however, ecmo blood flow rates (q ecmo ) are limited by the diameter of the shared lumen for drainage, and its effectiveness is very dependent on optimal placement of the reinfusion port so that oxygenated blood is directed toward the tricuspid valve, limiting its use in some patients during the acute phase of ards. in a recent large international report, it was used in only % of patients as the primary ecls approach [ ] . this review provides a summary of physiological concepts related to ecls, as well as the rationale and evidence supporting the two main forms of ecls for the treatment of ards: extracorporeal membrane oxygenation (ecmo) and extracorporeal co removal (ecco r). it also highlight evidence on complications, limitations, the ethical dilemmas in treating patients with ecls and discusses future key research questions and challenges for this technology. fig. three different modalities of ecls for acute respiratory distress syndrome. a femoro-jugular venovenous extracorporeal membrane oxygenation (vv-ecmo) which enables full oxygenation and carbon dioxide removal in the acute phase of ards. typical mechanical ventilation settings (eolia settings) aim to further protect the lung by reducing vt, rr, and ∆p; b dual-lumen jugular vv-ecmo is an alternative cannulation strategy; c extra-corporeal co removal, which may facilitate lung-protective ventilation by allowing a reduction of vt, pplat, rr, ∆p and mechanical power (supernova pilot settings) by ensuring partial carbon dioxide removal with marginal oxygenation in mild-to-moderate ards. vcv volumecontrolled ventilation, peep positive end-expiratory pressure, vt tidal volume, pplat plateau pressure, bipap/aprv biphasic positive airway pressure/ airway pressure release ventilation, rr respiratory rate, ∆p driving pressure, fr french, ards acute respiratory distress syndrome, ecls extracorporeal life support, mv mechanical ventilation, fdo fraction on oxygen in the sweep gas, mo, membrane oxygenator, qecmo (q e ) ecmo flow in l/min. major changes between the three settings are highlighted in bold font. a modified eolia settings with a set rr lower than in eolia. decreasing respiratory rate (< - breaths/min) to reduce mechanical power seems desirable, although it may be achieved in most ards patients only with deep sedation and neuromuscular blockade understanding the physiological determinants of gas exchange is crucial for optimal application of ecmo. the oxygen content of blood is dependent on haemoglobin level, the partial pressure of oxygen (po ), the oxyhemoglobin dissociation curve, and to a lesser extent, the dissolved oxygen. this has implications for the minimal blood flow required to provide full oxygenation (if required) [ ] , which is on the order of + liters per minute. the ability to oxygenate blood largely depends on the size and properties of the membrane oxygenator, q ecmo , and the difference in po between the blood flowing into the oxygenator and the po of the gas delivered to the membrane lung (sweep gas), typically oxygen or a blend of oxygen and air. the linear relationship between q ecmo and oxygen transfer favors the use of large drainage cannulas ( ) ( ) ( ) ( ) ( ) ( ) ( ) to provide full oxygenation support. the drained venous blood oxygen saturation (i.e., pre-oxygenator oxygen saturation), is the second major component determining oxygen transfer during ecmo. it is affected by the recirculation (i.e. reinfused oxygenated blood which is withdrawn through the drainage cannula before it can circulate through the lung). recirculation can be minimized either by femoral-jugular cannulation with a sufficient distance between the two tips of the cannulas, or using a properly positioned jugular dual-lumen cannula [ ] . because the (well-oxygenated) blood returned to the right atrium from the membrane oxygenator mixes with the remaining native venous return, an increase in cardiac output at constant ecmo flow rates will result in decreased systemic arterial oxygenation when native lung gas exchange is sufficiently impaired. in a physiological study performed in ten severe ards patients receiving v f -v j ecmo, q ecmo /cardiac output ratio ≥ % was associated with adequate blood oxygenation and oxygen delivery [ ] . other factors that affect systemic oxygenation include the complex interplay between intrapulmonary shunt, oxygen fraction to the native lung, oxygen fraction to the membrane lung, and total oxygen consumption [ ] . at any given blood flow, carbon dioxide removal is more efficient than oxygenation. at physiological levels, the carbon dioxide content of a given volume of blood is substantially higher than the oxygen content, and thus, for a given ecmo flow rate a greater percent of the patient's co production can be removed compared with the percentage of the oxygen consumption that can be provided [ , ] . as well, co is more soluble than o , allowing it to diffuse across the membrane circuit with greater efficiency. to understand the performance of available ecco r devices, it is important to understand that co removal will increase with increases in co blood content, the partial pressure of venous co (pvco ), artificial lung surface area, as well as increases in sweep gas and blood flow through the membrane lung, although with ceiling effects for both. blood flow rates of - l per minute (l/min) may be sufficient to fully remove the entire co production of most patients, but insufficient to provide the patient's full o consumption. for a given membrane lung size and blood flow rate, co removal will be increased with increasing sweep gas flow rate up to ~ - l/min [ ] ; a high pco will increase the gradient for diffusion of co out of the membrane; and artificial blood acidification can increase the amount of co available to the membrane [ , ] . historically, ecmo was restricted to patients dying from refractory hypoxemia [ , ] ; however, recently it has become the standard of care in experienced icus for patients with very severe ards [ ] . beyond its ability to rescue patients with very severe gas exchange abnormalities not responding to standard treatment, the ecmo to rescue lung injury in severe ards (eolia) trial strongly suggested that the main benefit of ecmo is through ameliorating ventilator-induced lung injury (vili) [ ] . patients who were enrolled in the eolia trial due to severe respiratory acidosis (arterial ph < . with paco ≥ mmhg for > h), rather than solely due to severe hypoxemia, appeared to benefit most [ ] , likely due to a reduction in ventilator-induced lung injury (vili) secondary to decreased tidal volume (vt), respiratory rate (rr), plateau pressure (pplat), driving pressure (∆p), and mechanical power [ , , ] . ecmo has a number of beneficial effects. minimizing hypoxemia decreases tissue hypoxia, which may reduce organ dysfunction including neurocognitive sequelae [ ] . ecmo decreases respiratory acidosis and right ventricular afterload and, therefore increase cardiac output [ ] . moreover, ecmo may reduce diaghragmatic myotrauma, by improving blood gases, hence decreasing respiratory drive. keeping patients ambulatory when ecls is used as a bridge to lung transplantation has been reported, but it is as yet unclear whether such a strategy is beneficial in ards patients [ ] . if this strategy is applied, then close monitoring of respiratory drive [ ] appears desirable to prevent additional lung injury due to patient respiratory effort [ ] . ideally, ecmo should be used in patients meeting eolia criteria (tables and ) after proven conventional management (including lung protective mechanical ventilation [ ] and prone positioning [ ] ) for severe ards have been applied and failed [ , ] . less frequently, rescue ecmo may be deployed when a patient is too unstable for prone positioning, or when this is the only way to facilitate safe transport from a non-expert centre that is unable to apply evidence-based conventional practices [ ] . lastly, employing ecmo when severe right heart failure, or other severe decompensation occurs, so-called salvage ecmo (referred to as "rescue" in eolia) should be avoided, where possible, as it is associated with higher mortality [ ] . when ecls is applied at relatively low blood flow (e.g., - ml/min) it can provide substantial co elimination (~ - % of total co production), albeit with marginal improvement in oxygenation. under these conditions, the technique is referred to as extra-corporeal co removal (ecco r). the rationale for using ecco r in ards is to facilitate lung-protective ventilation by allowing a reduction of vt, pplat, rr, ∆p and mechanical power [ ] ; the extent of lung protection depends on the volume of co that can be removed by the device [ ] . there is currently limited evidence to support the use of ecco r for ards outside the research setting [ , ] . first successfully deployed in a patient with ards in , ecmo gained momentum due to two unrelated events in : ( ) the influenza a(h n ) pandemic, in which national observational cohorts from france [ ] , italy [ ] , united kingdom (uk) [ ] , australia and new zealand [ ] , reported unexpected low mortality ( - %) in severely ill ards patients treated with ecmo; and, ( ) publication in of the cesar trial conducted in the uk [ ] , which evaluated a strategy of transfer to a single-center which had ecmo capability versus a strategy in which patients were treated conventionally at designated treatment centers ( table ). the primary endpoint (composite of mortality or severe disability six months after randomization) was lower for the patients randomized to the ecmo group ( % vs. %, p = . ). however, the study had numerous methodological issues. for example, many patients randomized to the ecmo arm did not receive ecmo (by design) and lung protective ventilation was not mandated in the control group. the more recent multicenter, international eolia [ ] trial has helped to define the role and safety of ecmo in managing severe ards, despite the fact that it was not "traditionally positive" [ ] . patients who fulfilled inclusion criteria ( table ) were randomized to standard of care, including protocolized mechanical ventilation (n = ), or to ecmo (n = ) with protocolized reduction of ventilator pressures, volumes, and respiratory rates. ninety percent of standard care patients and % of ecmo patiens received a trial of prone positioning at some time during their course. cross-over (i.e., receiving ecmo in the standard care group) was restricted to patients who were profoundly hypoxemic or hemodynamically unstable. the trial was stopped early for futility; there was an non-significant % absolute difference in -day mortality (p = . ). ecmo-treated patients had a significant reduction of cardiac failure, renal failure, and need for dialysis. there was a similar incidence of hemorrhagic stroke in the two groups. following the publication of eolia, goligher et al. re-analysed the results of the trial using a bayesian approach, [ ] which demonstrated a high likelihood of a table proposed indications and contraindications to ecmo for ards a after proven conventional management (including lung protective mechanical ventilation, prone positioning and possibly neuromuscular blockade) for severe ards have been applied and failed. less frequently, rescue ecmo may be deployed when a patient is too unstable for prone positioning, or when this is the only way to facilitate safe transport from a non-expert centre that is unable to apply evidence-based conventional practices b with respiratory rate increased to breaths per minute and mechanical ventilation settings adjusted to keep a plateau airway pressure of ≤ cm of water [ ] . patients randomised to ecmo had more days alive out of the icu and without respiratory, cardiovascular, renal and neurological failure. the eolia trial [ ] , the post hoc bayesian analysis [ ] , and systematic reviews and meta-analysis [ , ] all consistently supported the use of venovenous ecmo in adults with severe ards treated in expert centers. as stated in the editorial addressing the bayesian analysis, it is no longer a question of "does ecmo work? because that question appears to be answered but by how much does ecmo work, in whom, and at what cost?" [ ] . ecmo has played an important role during previous respiratory viral outbreaks [ ] . in a non-randomized study, transfer to an ecmo center was associated with lower hospital mortality compared with matched non-ecmo-referred patients [ ] . similarly, a retrospective chart review of middle east respiratory syndrome coronavirus (mers-cov) patients with refractory respiratory failure reported a lower in-hospital mortality rate in patients who received ecmo compared with those who received conventional oxygen therapy [ ] . due to resource and human constraints, ecmo cannot easily be employed extensively in such outbreaks. widespread application of proven conventional management approaches (i.e., protective mechanical ventilation, and prone positioning) before ecmo, and strict selection of patients most likely to benefit [ , ] are all key since any health system could be rapidly overwhelmed if large numbers of patients require ecmo. a recent study reported results on patients under the age of who fulfilled eolia trial criteria and received ecmo for very severe covid- -related ards [ ] . contrary to results early in the pandemic suggesting dismal outcomes for ecmo-treated covid- patients [ ] , the estimated probability of death days post-ecmo initiation was % ( % ci - %) [ ] . these results were similar to those from the eolia trial ( % at day ) [ ] and from the large prospective lifegard registry ( % at day ) [ ] . a large (n = ) registry study of ecmo for covid- involving predominantly respiratory failure, yielded an estimated cumulative incidence of in-hospital mortality of . % ( % ci . - . ) at days after initiation of ecmo, offering provisional support for the use of ecmo in highly selected patients with covid- [ ] . a very recent study identified a subgroup of patients with covid- -related ards characterised by low static compliance of the respiratory system and high d-dimer concentration that have a markedly increased mortality compared with other patients ( % vs. %) [ ] . these patients may potentially be considered for wider use of ecmo. investigation of the potential benefits of ultra-protective ventilation [ ] have led to renewed interest in ecco r. the technique has markedly improved in recent years [ ] , using more biocompatible circuits [ , ] , duallumen heparin-coated catheters with a diameter closer to dialysis catheters than to ecmo cannulas [ ] , and ultrasonography-guided catheter insertion. ecco r allows for a reduction in vt, pplat, ∆p [ ] , mean minute ventilation [ ] , and therefore enhances protective or ultra-protective ventilation [ ] . an increase in positive end-expiratory pressure (peep) to counteract derecruitment, induced by the tidal volume reduction [ ] , appears desirable. in this context, ecco r may be associated with a significant reduction of systemic and pulmonary inflammatory mediators [ ] . the strategy of ultraprotective lung ventilation with extracorporeal co removal (supernova) pilot study included patients with moderate-to-severe ards in icus. ecco r allowed a significant decrease in mechanical power with reductions of pplat ( to cmh o), vt ( to ml/kg), rr ( to breaths/min), and minute ventilation ( to l/min) [ ] . despite the significant reduction of minute ventilation, ph was maintained > . , and the increase in paco was < % from baseline. however, this strategy may not benefit all patients equally [ , ] , as the lung-protective benefits of ecco r increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance [ ] . therefore, these patients [ ] should preferentially be enrolled in randomized controlled trials, and worsening hypoxemia, reported in up to % of patients [ ] should be addressed. the hypoxemia can be secondary to a decreased mean airway pressure, and a lower ventilation-perfusion ratio, or due to a lower partial pressure of alveolar oxygen due to a decreased lung respiratory quotient and hypoventilation in the native lung [ ] . the co removal performance and device-related adverse events differ across available ecco r devices [ ] . the supernova pilot study used three different devices [ ] . a lower incidence of membrane clotting was reported with two higher flow ( - ml/min) devices ( %), with significantly higher rates of adverse events with the low blood flow device ( - ml/ min), despite similar anticoagulation regimens [ , ] . although theoretically very appealing, the impact on outcomes of a strategy combining ultra-protective ventilation and ecco r is unknown, as only physiological proof-of-concept and feasibility studies are available; randomized controlled trials are ongoing ( table ) . interestingly, the xtravent study, which used a pumpless arterio-venous ecco r device in moderate ards, observed similar mortality between the intervention group ( patients ventilated with ml/kg predicted body weight (pbw) and ecco r) and the control group ( patients ventilated with ml/kg pbw) [ ] . of note, in a post hoc analysis, the treated subgroup with a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (pao /fio ) < mmhg achieved earlier weaning than the controls. the main goals of ecmo are to provide adequate gas exchanges while minimizing vili. in the acute phase of ards, using a large venous drainage cannula-a prerequisite for high q ecmo (> l/min)-enables adequate oxygenation while applying "ultra-protective lung ventilation". how much the intensity of mechanical ventilation should be decreased, and whether or not we should maintain the lungs open to avoid complete lung collapse, are still a matter of debate [ , ] . some degree of ventilation, while maintaining peep ≥ cmh o, during ecmo improved survival in a retrospective study [ ] . on the other hand, a larger reduction in mechanical ventilation intensity through lower driving pressure [ ] was associated with lower mortality and near-apneic ventilation resulted in fewer histological lesions of lung injury in an animal model [ ] . similarly, decreasing respiratory rate (< - breaths/min) to reduce mechanical power seems desirable [ , ] , although it may be achieved in most ards patients only with deep sedation and neuromuscular blockade. this strategy may be less appropriate as the patients' course progresses as it may delay physical and cognitive rehabilitation. future trials should assess these strategies in severe ards patients during ecmo. several techniques have been used to optimize lung recruitment while minimizing lung injury during ecmo. first, individualization of peep during ecmo using transpulmonary pressure measurements [ ] or electrical impedance tomography (eit) [ ] appear promising. second, some centers currently perform prone positioning during ecmo with a goal of reducing vili [ , ] . two recent retrospective series of severe ards patients showed that prone positioning, while on-ecmo demonstrated higher ecmo-weaning and survival rates [ , ] . however, randomized controlled trials of prone positioning during ecmo are needed before recommending this practice routinely. lastly, the use of pressure-controlled ventilation [ ] may allow for easy detection of patient recovery by observing increases in vt during ecmo. when the patient is stabilized, preventing diaphragm atrophy by introducing spontaneous breathing activity may be desirable. however, even during this rehabilitation phase of severe ards, the respiratory drive of the patient may still be (too) high, which may be controlled by increasing sweep gas flow which lowers paco [ ] ; the efficacy of this maneuver may be assessed by measurement of patient effort and work of breathing. ventilation strategies on ecmo integrating repiratory drive monitoring deserve investigation. patients receiving ecmo may also benefit from less sedation and early rehabilitation, and retrospective studies have found that rehabilitation, including mobilization, during ecmo was feasible and safe, even in patients with very high severity of illness [ , ] . in some circumstances, severe hypoxemia persits under vv-ecmo. this situation requires a multi-step approach [ ] that should begin with a complete circuit check, followed by ensuring adequate positiniong of cannulas to minimize blood recirculation and optimize the ratio of ecmo blood flow to cardiac output. moderate hypothermia to decrease tissue oxygen utilization (with a depressant effect on cardiac output). short-acting beta-blockers have been used for refractory hypoxemia to decrease the extracorporeal blood flow-to-systemic blood flow ratio (q e :q s ) [ ] , which will improve arterial oxygenation but will simultaneously decrease cardiac output, and therefore will have an overall variable effect on tissue oxygen delivery and so should be approached with caution if oxygen delivery is not directly measured, especially given the very limited data supporting this approach. packed red blood cells may be transfused with the idea of maximizing oxygen delivery. however, the optimal transfusion threshold for these patients has not been established and transfusion is associated with adverse outcomes in the setting of ards [ ] . prone positioning (pp) during ecmo may also be effective by increasing the proportion of poorly-aerated areas in dependent lung regions [ ] . further data are needed to better understand the risk-tobenefit ratio of this intervention. ecmo weaning, which is typically performed before weaning from mechanical ventilation [ ] , should be tested when native lung function has sufficiently recovered allowing adequate oxygenation and safe (or protective) mechanical ventilation settings (e.g., ventilator fio ≤ %, sweep gas flow < l/min, and vt ≥ . ml/ kg pbw with pplat ≤ cmh o or ∆p ≤ cmh o) and involves regular trials with the sweep gas turned off. a detailed ecmo weaning algorithm is proposed in fig. . based on eolia, current weaning success criteria for safe decannulation from ecmo [ ] are: pao ≥ mmhg, sao ≥ %, with fio ≤ %; paco ≤ mmhg or ph ≥ . , with respiratory rate ≤ /min; pplat ≤ cmh o; and no signs of acute cor pulmonale. modern management of vv-ecmo with heparincoated surfaces and high q ecmo have allowed for a substantial decrease in systemic anticoagulation [ ] . unfractionated heparin (target aptt - s) or anti-xa activity ( . - . iu/ml) are commonly used [ ] . however, these may need to be revised upwards in high inflammatory syndromes or infections associated with vascular injury, such as covid- -related ards, although the data on this are not clear [ ] . close daily monitoring to reduce ecls-related complications is mandatory, and requires intensive education and training (fig. ) . although relatively infrequent in the eolia trial [ ] , intracranial hemorrhage is associated with poor outcomes. the rapidity with which co is reduced after ecls initiation has been implicated in development of neurological complications and the sweep gas flow through the oxygenator should be adjusted to avoid a drop in paco > mm hg/h over the first -h of ecmo in most patients [ , ] . similarly, interactions between the blood, the pump, and the artificial surfaces of the circuit and membrane generate blood trauma and activate coagulation and fibrinolysis pathways associated with increased inflammatory responses. daily monitoring of platelet count, fibrinogen, anticoagulation levels and other parameters are aimed at recognizing the onset of complications such as clotting, bleeding and hemolysis, and the need to change portions of the circuit. in addition, thrombosis and hemolysis appear to be more frequent with low-flow ecmo or ecco r. the clotting risk is directly related to the type of device, the extracorporeal blood flow, and the size of the cannulas [ ] . lastly, the ecls population may be particularly susceptible to nosocomial infections because of concomitant critical illness, indwelling catheters, and prolonged hospitalization. management of infections during ecls is more challenging due to alterations in pharmacokinetics of antimicrobial agents in the presence of an extracorporeal circuit [ ] . an analysis of the international elso registry reported an association between higher annual ecmo volume and lower case-mix-adjusted mortality for ecmotreated neonates and adults [ ] a position paper [ ] by an international group of experts advocated for a regional and inter-regional ecmo network of hospitals around an ecmo referral center with a mobile ecmo unit to retrieve the most severe patients. patients supported with ecmo generally have prolonged icu and hospital lengths of stay [ , , ] , which likely contribute to worse pulmonary function, quality of life, and psychological status. however, the long-term prognosis after ecmo for ards has been insufficiently evaluated. patients in the ecmo arm of [ ] . venovenous ecmo can be associated with complex ethical dilemmas, particularly in situations where patients are unlikely to recover sufficiently to transition to conventional mechanical ventilation, and are not candidates for lung transplantation [ ] . in these circumstances, criteria regarding continuation or withdrawal of ecmo are not strictly established and may differ among caregivers, ecmo centers, and countries. in a recent survey of physicians from countries across continents, these decisions were strongly influenced by whether a patient's or surrogate's wishes were known, the level of consciousness of the patient, and perceived "futility" of the clinical situation [ ] . weighing the potential benefits and risks of ecmo using predictive survival models [ , ] , and improving doctor-patient/surrogate communication surrounding the benefits and limitations clinical management and daily monitoring of ecmo for ards. vv-ecmo venovenous extracorporeal membrane oxygenation, vcv volumecontrolled ventilation, peep positive end-expiratory pressure, vt tidal volume, p plat plateau pressure, rr respiratory rate, ∆p driving pressure, bipap/ aprv biphasic positive airway pressure/airway pressure release ventilation, p high high pressure, p low low pressure, ufh unfractionated heparin, aptt activated partial thromboplastin time, pk/pd pharmacokinetic/pharmacodynamics, rass richmond agitation-sedation scale, p . drop in airway pressure observed during the first ms of an inspiratory effort made against the occluded airway opening, pven venous pressure (i.e. inlet pressure) on ecmo, part arterial pressure (i.e., outlet pressure) on ecmo, ∆p on ecmo trans-membrane oxygenator pressure gradient or pressure drop, i.e., the difference betweenthe pressure of the blood at the inlet and at the outlet of the membrane lung, usually - mmhg. a modified eolia settings with a set rr lower than in eolia of ecmo before its initiation are crucial. shared decision-making with patients and family regarding end-oflife decisions on ecmo are recommended [ ] . the eolia trial took . years to enroll patients. given the logistical hurdles, a new randomized controlled trial comparing ecmo versus conventional mechanical ventilation management seems highly unlikely. the major question now is rather: "how to provide better ecmo care?". the management of mechanical ventilation during ecmo warrants further investigation. studies are needed to investigate the impact of strategies such as larger reductions in mechanical ventilation intensity, frequent use of prone positioning, close control of respiratory drive, and ecmo without invasive mechanical ventilation. more work is needed to decrease the burden of ecmo-induced coagulopathy and associated bleeding, which is particularly important for ecco r. this includes work on improved biocompatible materials to reduce hemorrhagic or thrombotic adverse events; on pump technology to minimize shear stress, and hemolysis especially at low flows [ ] . beyond safety, the degree of benefit of ultra-protective ventilation remains to be proven [ ] and large clinical trials to investigate the impact of ecco r for ards on outcomes are urgently needed (table ) . moreover, future research should focus on the selection of patients who will most likely benefit from the use of extracorporeal support [ , ] . importantly, research networks, such as the international ecmo network (ecmonet; www.inter natio nalec monet work.org), and large ecmo registries, such as the registry of the extracorporeal life support organization (elso; www.elso.org), will be critical to achieving these future research aims. although vv-ecmo is now a safe and viable strategy for severe ards when performed in experienced centers, it should not be a substitute for proven conventional ards management. therefore, the initial management of patients with severe ards should always include lung protective ventilation and prone positioning, unless contraindicated or not technically feasible [ ] . future efforts in the field should focus on the improvement of ecmo care and elucidation of ecco r on 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cohort study and propensity-matched analysis the italian ecmo network experience during the influenza a(h n ) pandemic: preparation for severe respiratory emergency outbreaks referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza a(h n ) extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial learning from a trial stopped by a data and safety monitoring board extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc bayesian analysis of a randomized clinical trial ecmo for severe ards: systematic review and individual patient data meta-analysis venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis time for clinicians to embrace their inner bayesian?: reanalysis of results of a clinical trial of extracorporeal membrane oxygenation extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. the respiratory extracorporeal membrane oxygenation survival prediction (resp) score the preserve mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with covid- : a retrospective cohort study poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ards) due to coronavirus disease (covid- ): pooled analysis of early reports extracorporeal membrane oxygenation support in covid- : an international cohort study of the extracorporeal life support organization registry pathophysiology of covid- -associated acute respiratory distress syndrome: a multicentre prospective observational study ventilator-induced lung injury low-flow assessment of current ecmo/ecco r rotary blood pumps and the potential effect on hemocompatibility feasibility and safety of lowflow extracorporeal co removal managed with a renal replacement platform to enhance lung-protective ventilation of patients with mild-tomoderate ards lower tidal volume strategy (≈ ml/kg) combined with extracorporeal co removal versus 'conventional' protective ventilation ( ml/kg) in severe ards: the prospective randomized xtravent-study low respiratory rate plus minimally invasive extracorporeal co removal decreases systemic and pulmonary inflammatory mediators in experimental acute respiratory distress syndrome ventilator-related causes of lung injury: the mechanical power feasibility and safety of extracorporeal co removal to enhance protective ventilation in acute respiratory distress syndrome: the supernova study determinants of the effect of extracorporeal carbon dioxide removal in the supernova trial: implications for trial design feasibility and safety of lowflow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome understanding hypoxemia on ecco r: back to the alveolar gas equation should patients with acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation have ventilatory support reduced to the lowest tolerable settings? no should patients with acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation have ventilatory support reduced to the lowest tolerable settings? yes mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis : mechanical ventilation during ecmo near-apneic ventilation decreases lung injury and fibroproliferation in an acute respiratory distress syndrome model with extracorporeal membrane oxygenation mechanical ventilation strategy guided by transpulmonary pressure in severe acute respiratory distress syndrome treated with venovenous extracorporeal membrane oxygenation bedside contribution of electrical impedance tomography to set positive end-expiratory pressure for ecmo-treated severe ards patients prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: time for a randomized trial prone positioning in severe ards requiring extracorporeal membrane oxygenation intensive care physiotherapy during extracorporeal membrane oxygenation for acute respiratory distress syndrome recent developments in the management of persistent hypoxemia under veno-venous ecmo low-dose versus therapeutic anticoagulation in patients on extracorporeal membrane oxygenation: a pilot randomized trial the early change in paco after extracorporeal membrane oxygenation initiation is associated with neurological complications brain injury during venovenous extracorporeal membrane oxygenation ecls-associated infections in adults: what we know and what we don't yet know association of hospitallevel volume of extracorporeal membrane oxygenation cases and mortality. analysis of the extracorporeal life support organization registry position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients mortality and costs following extracorporeal membrane oxygenation in critically ill adults: a population-based cohort study long-term outcomes of pandemic influenza a(h n )-associated severe ards understanding ethical decisions for patients on extracorporeal life support practice patterns and ethical considerations in the management of venovenous extracorporeal membrane oxygenation patients: an international survey low-flow assessment of current ecmo/ecco r rotary blood pumps and the potential effect on hemocompatibility feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ards patients ecmo for immunosuppressed patients with acute respiratory distress syndrome: drawing a line in the sand saying no until the moment is right: initiating ecmo in the eolia era extracorporeal organ support: from technological tool to clinical strategy supporting severe organ failure we thank savannah soenen for the creation of the figures. drafting of the manuscript: c, s, s, b. critical revision of the manuscript for important intellectual content: all authors. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.received: september accepted: october key: cord- -ormm rax authors: calcaterra, domenico; heather, beth; kohl, louis p.; erickson, heidi l.; prekker, matthew e. title: bedside veno‐venous ecmo cannulation: a pertinent strategy during the covid‐ pandemic date: - - journal: j card surg doi: . /jocs. sha: doc_id: cord_uid: ormm rax background: patient selection and cannulation arguably represent the key steps for the successful implementation of extracorporeal membrane oxygenation (ecmo) support. cannulation is traditionally performed in the operating room or the catheterization laboratory for a number of reasons, including physician preference and access to real‐time imaging, with the goal of minimizing complications and ensuring appropriate cannula positioning. nonetheless, the patients' critical and unstable conditions often require emergent initiation of ecmo and preclude the safe transport of the patient to a procedural suite. aims: therefore, with the objective of avoiding delay with the initiation of therapy and reducing the hazard of transport, we implemented a protocol for bedside ecmo cannulation. matherial and methods: a total of patients required ecmo support at hennepin county medical center between march and december . twenty‐eight ( %) required veno‐venous support and were all cannulated at the bedside. overall survival was % with no morbidity or mortality related to the cannulation procedure. conclusion: in the current pandemic, the strategy of veno‐venous bedside cannulation may have additional benefits for the care of patients with refractory acute respiratory distress syndrome due to coronavirus disease‐ , decreasing the risk of exposure of health care worker or other patients to the novel severe acute respiratory syndrome coronavirus‐ occurring during patient transport, preparation, or during disinfection of the procedural suite and the transportation pathway after ecmo cannulation. veno-venous (vv) extracorporeal membrane oxygenation (ecmo) has been recognized as a potentially life-saving therapy for patients with refractory acute respiratory distress syndrome (ards) secondary to pneumonia and its use in adults has increased exponentially following the influenza a (h n ) pandemic in . [ ] [ ] [ ] [ ] [ ] the extracorporeal life support organization has published comprehensive guidelines defining the appropriate clinical indications for vv-ecmo use and has established detailed protocols and quality measures to ensure appropriate implementation of therapy. , extracorporeal circulation in vv-ecmo is traditionally obtained with the insertion of two venous cannulas either with the internal jugularfemoral or the femorofemoral configuration. , , in recent years, a technique using a single-bicaval dual-lumen catheter (avalon elite; maquet inc, rastatt, germany) with access through the right internal jugular vein (ijv) has become available as an alternative method to the traditional double-venous cannulation strategy. , , the single insertion site, which may reduce the risk of bleeding and infection, the location of the insertion site in the neck, which may facilitate patients' prone positioning as needed, and possibly the more efficient oxygenation, most likely related to the lesser incidence of the phenomenon of "recirculation," account for the advantages of using a single dual-lumen cannula vs a double cannulation strategy. , , [ ] [ ] [ ] on the other hand, the perceived technical difficulty of the internal jugular venous cannulation using a large bore cannula ( or fr, both with an insertable length of cm) is seen as a potential disadvantage. for this reason, the dual-lumen catheter ijv placement is traditionally performed in the operating room or the catheterization laboratory with the assistance of fluoroscopy and transesophageal echocardiography. , , in , we implemented a strategy of routine bedside ecmo cannulation at hennepin county medical center. an internal committee was created with the objective of designing protocols and determining the logistics of the cannulation procedure. dry runs were simulated in the surgical intensive care unit (icu) until the optimal cannulation protocol was defined. a total of patients required ecmo support at hennepin county medical center between march and december . of these, ( %) patients were cannulated for vv support, all at the bedside. a dual-lumen bicaval cannula (avalon elite; maquet inc) was used in cases; a two cannula approach using the right ijv and the femoral vein was selected in cases due to patient-specific factors, such as a high native cardiac output. of the vv-ecmo cases, the average age was years (range, - ), ( %) were women, and the average body surface area (bsa) was . m (range, . - . ). cannula size selection was based on the patient's bsa. the indication for vv-ecmo was ards in all cases; the etiology of ards was pneumonia (n = ; %), massive aspiration (n = ; %), blunt trauma (n = ; %), and drowning (n = ; %). bedside cannulation was successful in of cases ( %), and there was no mortality or morbidity associated with the procedure. the failed cannulation was in the case of a young woman who hanged herself. percutaneous access to the right ijv failed due to massive subcutaneous emphysema; she was cannulated using a peripheral venoarterial configuration via the femoral vessels. ecmo blood flow achieved was greater than % of native cardiac output in all cases. the median days of vv-ecmo support were (range, - ). a total of of patients ( %) undergoing vv-ecmo support survived to hospital discharge. there was no occurrence of thrombotic or hemorrhagic complications. we designed a process of in situ vv-ecmo cannulation based on the layout of our icu where patients with refractory respiratory failure are routinely hospitalized (figure ). we utilize a portable fluoroscopy bed which is placed to the side of the icu bed ( figure ). after moving the patient from the icu to the fluoroscopy bed, the medical equipment is positioned around the patient to allow convenient access to the right side of the neck as the cannula insertion site ( figure ). the procedure is completed under sterile conditions with fluoroscopic guidance. fluoroscopic guidance represents our preferred imaging method since it may offer the highest level of safety. , however, in the absence of conditions allowing routine use of fluoroscopy at the bedside, the procedure can also be safely performed with a transthoracic echocardiogram (tte) to confirm guidewire and cannula positioning. , [ ] [ ] [ ] appropriate positioning of the guidewire can be confirmed with subcostal views, making sure that the wire is advanced into the retrohepatic inferior vena cava (ivc). , [ ] [ ] [ ] [ ] [ ] [ ] alternatively, imaging by portable chest x-ray can also be used to spotcheck guidewire and cannula position. cannulation best practices using our approach are listed in table . we always use real-time ultrasound visualization for the puncture of (table ) . after serial dilation of the skin and soft tissue at the cannula insertion site, the ijv is cannulated with fr through fr dilators. the cannula is inserted under imaging guidance ensuring no resistance is encountered while the catheter is advanced through the right atrium into the ivc. the cannula is connected to the ecmo circuit with meticulous deairing and is secured to the skin once final manual manipulation is made to ensure adequate extracorporeal blood flow and desired arterial oxygenation (table ) . anticoagulation during therapy is maintained with an infusion of ufh, titrated for antifactor xa activity goal of . to . . antifactor xa monitoring represents the institutional preference, since assessing the common pathway of the coagulation cascade may be the most reliable measure of the anticoagulation status. [ ] [ ] [ ] | discussion in our experience, the procedure of bedside vv-ecmo cannulation was safe and effective. we had only one case of failed ijv single-cannula insertion which required veno-arterial cannulation using the common f i g u r e bedside cannulation with the use of fluoroscopy and transthoracic echocardiogram (tte). equipment is positioned around the patient allowing the operator and assistant to be positioned at the head of the bed. in the absence of the availability of fluoroscopy, the procedure can be completed with the use of a portable chest x-ray in combination with tte. echo, echocardiography; ecmo, extracorporeal membrane oxygenation; icu, intensive care unit f i g u r e final arrangement. ecmo, extracorporeal membrane oxygenation; icu, intensive care unit femoral artery and vein due to anatomic constraints. all procedures were performed in the icu under fluoroscopic and echocardiographic guidance. our set up allowed the efficient utilization of fluoroscopy by using a mobile, x-ray compatible bed (figures and ) . we selected the use of a bicaval dual-lumen cannula whenever indicated to facilitate adequate ecmo flow and optimize blood oxygenation by reducing "recirculation." , , the selection of double-venous cannulation was based on operator preference due to patient characteristics, such as a body mass index above , or in situations of patient's hemodynamic conditions, which represented a concern for maintaining adequate extracorporeal circulation, such as a cardiac index (ci) above . l/min/m . although there is a lack of randomized trials comparing the effective- • dilators are advance smoothly through the insertion site for a few cm ( ) ( ) ( ) to obtain proper dilatation of skin incision and venipuncture. • when the biggest dilators are utilized, the skin entry site requires to be enlarged with a surgical scalpel to allow smooth sliding of dilators removing any resistance to advancement at the skin entry site • the placement of the guidewire is reconfirmed by imaging to ensure the adequate position of the cannula deep into the ivc. • the avalon elite cannula is primed with heparinized saline and advanced over the guidewire under imaging guidance. • the tip of the cannula should be located approximately cm below the right hemidiaphragm to ensure that the inflow port, which is at cm from the tip, is positioned in the right atrium. • location of the inflow port in the right atrium with jet anteriorly directed towards the tricuspid valve is confirmed by tte imaging • once the proper position and orientation of the cannula are obtained, the two attachment ports are connected to the ecmo circuit with meticulous deairing. it is recommended that tubing from the ecmo circuit is marked with blue tape to identify the outflow line carrying deoxygenated blood (from the patient to the oxygenator) and with red tape for the return inflow line carrying oxygenated blood (from the oxygenator to the patient). red tubing is connected to cannula inflow (marked by an arrow pointing to the patient) and blue tubing is connected to cannula outflow (marked by an arrow pointing away from the patient) • the cannula needs to be positioned to the side of the neck maintaining the inflow port anteriorly to obtain the appropriate orientation of blood inflow in the right atrium towards the tricuspid valve • blood flow is initiated at a slow rate to avoid sudden intravascular volume shift that would cause sudden hypotension. it is crucial to notice the difference between bright blood flowing in the anterior port compared to dark blood flowing in the posterior port. • appropriate securing of the cannula to the skin is extremely important to avoid catheter's migration and rotation. • we apply to stitches that after being tied to the skin are looped around each one of cannula ports passing in the "crotch" between the two ports note: technical tips of cannulation: the procedure requires the presence of two operators familiar with the use of the cannula and its insertion kit. it is important to prepare surgical instruments, tubing clamps, and all the needed items ( however, cannulation can also be safely completed using echocardiographic imaging with tte or even using portable chest x-ray, which can be both routinely arranged at any health care facility. the use of fluoroscopy at the bedside can be challenging if logistics are not sui- extracorporeal membrane oxygenation for influenza a (h n ) acute respiratory distress syndrome extracorporeal membrane oxygenation for pandemic h n respiratory failure management of acute respiratory complications from influenza a (h n ) infection: experience of a tertiary-level intensive care unit referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza a (h n ) veno-venous ecmo: a synopsis of nine key potential challenges, considerations, and controversies extracorporeal life support organization guidelines the extracorporeal life 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for insertion of dual lumen bicaval cannulae for venovenous extracorporeal membrane oxygenation transesophageal echocardiography-guided technique for extracorporeal membrane oxygenation dual-lumen catheter placement avalon bicaval dual-lumen cannula for venovenous extracorporeal membrane oxygenation: survey of cannula use in france transthoracic echocardiography visualization of bicaval dual lumen catheters for veno-venous extracorporeal membrane oxygenation right ventricular loop indicating malposition of j-wire introducer for double lumen bicaval venovenous extracorporeal membrane oxygenation (vv ecmo) cannula veno-venous extracorporeal membrane oxygenation (v v ecmo): indications, preprocedural considerations, and technique extracorporeal membrane oxygenation by single-vessel access in adults: advantages and limitations anticoagulation management and antithrombin supplementation practice during veno-venous extracorporeal membrane oxygenation: a worldwide survey anticoagulation for extracorporeal membrane oxygenation: between the rock and the hard place anticoagulation practices during venovenous extracorporeal membrane oxygenation for respiratory failure. a systematic review cannulation strategies for percutaneous extracorporeal membrane oxygenation in adults comparison of the avalon dual-lumen cannula with conventional cannulation technique for venovenous extracorporeal membrane oxygenation hemodynamic evaluation of avalon elite bi-caval dual lumen cannulas and femoral arterial cannulas right ventricular rupture and tamponade caused by malposition of the avalon cannula for venovenous extracorporeal membrane oxygenation the authors declare that there are no conflict of interests. this study meets the ethical guidelines, including adherence to the legal requirements of the study country. http://orcid.org/ - - - key: cord- -hyyw eln authors: huette, pierre; beyls, christophe; guilbart, mathieu; coquet, alexandre; berna, pascal; haye, guillaume; roger, pierre-alexandre; besserve, patricia; bernasinski, michael; dupont, hervé; abou-arab, osama; mahjoub, yazine title: extracorporeal membrane oxygenation for respiratory failure in covid- patients: outcome and time-course of clinical and biological parameters date: - - journal: can j anaesth doi: . /s - - -z sha: doc_id: cord_uid: hyyw eln nan the place of extracorporeal membrane oxygenation (ecmo) therapy in the coronavirus disease (covid- ) outbreak is undefined. our tertiary hospital is situated in picardy (northern france), one of the areas most affected by the outbreak in france. we report a prospective caseseries that describes the clinical course of patients with covid- with respiratory failure requiring veno-venous ecmo between march and april . after ethical approval, we prospectively collected data on consecutive covid- patients (confirmed with reverse transcription polymerase chain reaction testing) admitted to our referral centre for ecmo therapy. demographic, biological, and clinical data were collected during ecmo therapy. data on outcomes were reported. fourteen patients were eligible for ecmo during this period; two of them died in peripheral centres during ecmo cannulation (one patient was in refractory septic shock and one patient had a massive pulmonary embolism ten ( %) patients were weaned from ecmo and two patients died under ecmo. duration of ecmo therapy was [ - ] days. nine patients ( %) were weaned from mechanical ventilation. overall, eight patients ( %) were discharged from the icu and four ( %) died (figure) . lung-protective ventilation was maintained during ecmo. duration of mechanical ventilation was [ - ] days and ten ( %) patients developed ventilator associated pneumonia (vap). all patients received heparin treatment for an anti-xa level target of . - . uiÁml - . thrombotic events occurred in ( %) patients: deep vein thrombosis (four patients), renal replacement therapy (rrt) circuit clotting (two patients), complete clotting of the ecmo circuit (three patients), and pulmonary embolism (two patients). eleven ( %) patients had kidney disease: improvement of global outcomes or classification of acute kidney injury (aki) and eight ( %) required rrt (etable as esm). in this case-series of patients with covid- -related respiratory failure, we found a high rate of ecmoweaning. complications such as aki, thrombosis, and vap occurred frequently. a high risk of thrombosis for covid- patients under ecmo has been suggested previously. at the initiation of ecmo, patients had low lymphocyte counts that increased progressively until weaning, in accordance with previous reports showing that most severe covid- cases had persistently low lymphocyte counts. in our experience, a reduction in fibrinogen correlates with improvements in oxygenation. decreasing fibrinogen levels may be a marker for improvement in the coagulopathy and a reduction in disease severity, with improvement in oxygenation. studies with a larger sample size are needed to draw formal conclusions about the benefit of ecmo therapy for covid- -related respiratory failure. disclosures none. editorial responsibility this submission was handled by dr. sangeeta mehta, associate editor, canadian journal of anesthesia. planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases covid- does not lead to a ''typical'' acute respiratory distress syndrome extracorporeal membrane oxygenation for covid- -associated severe acute respiratory distress syndrome and risk of thrombosis clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china high risk of thrombosis in patients in severe sars-cov- infection: a multicenter prospective cohort study publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -lcgeingz authors: nan title: th international symposium on intensive care and emergency medicine: brussels, belgium, - march date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: lcgeingz nan introduction: increasing evidence supports a central role for "immunosuppression" in sepsis. it is necessary to develop biomarkers of immune dysfunction that could help to identify patients at risk of poor outcomes [ ] . the decreased expression of human leucocyte antigen (hla)-dra is proposed as a major feature of immunodepression and its persistent decrease is associated with mortality in sepsis [ ] . in a previous study, we evidenced that fcer a (fc fragment of ige receptor ia) is the gene showing the lowest expression levels of the entire transcriptome in sepsis [ ] . here we studied the association between fcer a expression and mortality in infected surgical patients. methods: fcer a and hla-dra expression levels were quantified by droplet digital pcr in blood of infected surgical patients. patients died within days ( . %). spearman test was used to evaluate the association between gene expression and the sequential organ failure assessment (sofa) score. areas under receiver operating curves (auroc) were used to determine the gene expression cut-off values predicting mortality. kaplan-meier survival curves were obtained and differences in survival between groups were evaluated using the log rank test. cox regression was employed to assess mortality risk at days. results: gene expression levels of fcer a and hla-dra correlated inversely with patients' severity (r: - . p< . ; r: - . , p< . respectively). both genes showed significant aurocs to predict survival, but fcer a showed the best accuracy (fig. ) . patients with introduction: severe pulmonary and renal conditions such as acute respiratory distress syndrome (ards), respiratory failure, and deterioration in kidney function often occur in patients with nosocomial pneumonia (np). the emergence and course of infection is genetically determined, hence host genetic landscape may influence an ability to resist infection. methods: variants for genotyping were selected using the phewas catalog which presents genotypic data for caucasian patients, phenotypes and single nucleotide polymorphisms (snps) with p < . [ ] . snps with the lowest p-values for phenotypes with both, respiratory and renal manifestations were selected: intergenic variants rs and rs , rs (edil ) and rs (cyp a ). cyp a gene was associated with pneumonia and ards in our previous investigations, so we included in our analysis three sites of cyp a gene (rs , rs and rs ) studied on a smaller sample. genotyping was performed on sites for a sample results: allele rs -g of the cyp a gene was protective against ards and an increase in creatinine level (fig. ) . the rs -g allele was associated with lung complications and with the development of severe respiratory insufficiency (fig. ) . conclusions: the snps rs and rs can influence the aggravation of pulmonary and renal symptoms through genetically mediated response to infection. introduction: an uncontrolled inflammatory response plays a major role in the sepsis related organ dysfunction. mesenchymal stem cells(mscs) can improve survival of sepsis experimental models by modulating the inflammatory response. macrophages have been considered as important immune effector cells and their polarization imbalance aggravates the disordered inflammation reaction. the project aims to identify the effects of mscs on macrophages polarization against dysregulated inflammatory response. methods: raw . cells were plated in the lower chambers of transwell system in the presence or absence of lipopolysaccharide (lps). then, mscs were seeded in the upper chambers and incubation for different time. finally, transforming growth factor beta (tgfβ) receptor (tgf-βr) inhibitor was added in transwell system. the phenotype of raw . cells were analyzed by flow cytometry, the levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (elisa). results: our data showed that lps increased the level of interleukin (il)- in raw . cells (p< . ) (fig. ). in line with il- expression, lps induced the expression of m macrophage (p< . ). moreover, lps stimulated raw . cells co-culture with mscs in transwell system, mscs inhibited the expression of il- and m macrophages, while increased m macrophages (p< . ). compared with lps group, the concentration of tgf-Β was obviously increased in mscs treatment groups (p< . ), furthermore, there were no significantly difference between mscs directed and indicted groups. more significantly, tgf-βr inhibitor abolished the impact of mscs on lps stimulated raw . cells (p< . ) (fig. ) . conclusions: mscs polarized m macrophages into m macrophages and decreased pro-inflammatory cytokine levels by paracrining tgf-β. introduction: sepsis is dysregulated response to an infection, which can lead to progressive microcirculatory dysfunction, release of reactive oxygen intermediates (roi) and life-threatening organ dysfunction. our aim was to investigate the relationship between organ damage -characterized by the sequential organ failure assessment (sofa) scores, microcirculatory failure and roi production, in a large animal model of experimental sepsis. methods: fecal peritonitis was induced in anesthetized minipigs (n= ; . g/kg autfeces containing - x cfu bacteria i.p.), control animals (n= ) received sterile saline i.p. invasive hemodynamic monitoring and blood gas analyses were performed between - hrs, the signs for failure of circulatory, respiratory and urinary systems were evaluated in accordance with the sofa score. the microcirculatory perfusion rate in the sublingual region was measured by orthogonal polarization spectral imaging technique (cytoscan a/r). the leukocyte-origin roi production was determined by lucigenine (mostly o -. ) and luminol-based (h o ) chemiluminescence methods. results: between - hrs after induction the sofa score indicated moderate organ failure in animals (m: . ; p: . , p: . ) and the change was statistically significantly higher in pigs, suggesting severe organ dysfunction (m: . ; p: . , p: . ). the microcirculation was significantly deteriorated in all cases, independently of sofa score data. the h o production was significantly lower in septic animals as compared to controls, while the lucigenine enhanced roi production correlated with the sofa score-indicated moderate and severe organ dysfunction. conclusions: sublingual microcirculatory parameters are not correlating with the severity of sofa score-indicated organ dysfunction in abdominal sepsis. the measurement of roi production of the whole blood seems to be better biomarker for the detection of the progression of events from moderate to severe organ damages. introduction: the purpose of this study was to characterize differences in sepsis management in patients with and without left ventricular (lv) dysfunction. septic patients with lv dysfunction have higher mortality, and limited guidance exists for sepsis management of patients with lv dysfunction. the possibility exists that the cornerstones of sepsis management may contribute to these poor outcomes. methods: a retrospective chart review was conducted from may -january at two centers. adult patients who had a diagnosis of sepsis, were treated with vasopressors for > hours, and had an echocardiogram within months were included. patients were divided into two groups: reduced ejection fraction (ef) of < % and preserved ef defined as ef ≥ %. information about patient outcomes and sepsis management were collected. the primary outcome was the need for mechanical ventilation (mv). categorical and continuous data were analyzed using the chi-squared and mann-whitney u tests, respectively. the irb has approved this project. results: a total of patients with ef < % and patients with ef ≥ % were included. no significant differences in fluid management, vasoactive agent maximum rate or duration, or steroid use were observed. net fluid balance between low and preserved ef was positive . liters vs. . liters (p = . ), respectively. the number of patients that needed mv was higher in the low ef cohort ( % vs. %, p = . ), and this cohort had fewer mv-free days ( , iqr - vs. (iqr - ), p= . . conclusions: no significant differences were observed with regard to sepsis management, reflecting current guidelines. the significantly increased need for mv is a provocative result. a potential mechanism is the inability of a patient with reduced lv dysfunction to maintain appropriate cardiac and respiratory function in the face of fluid overload. prospective analysis of the role of fluid balance in septic patients with lv dysfunction is warranted. introduction: the relationship between myocardial injury and systemic inflammation in sepsis response is not well understood [ ] . it´s proposed to evaluate the association between myocardial injury biomarkers, high-sensitive troponin t (hs-ctnt) and n-terminal pro-brain natriuretic peptide (nt-probnp), with inflammatory mediators (il- , il- Β , il- , il- , il- / il- p , il a, il- and tnf-α ) and biomarkers, c protein reactive (cpr) and procalcitonin (pct), in septic patients methods: this was a prospective cohort study performed in three intensive care units, from september to september enrolling patients with sepsis (infection associated with organ dysfunction), and septic shock (hypotension refractory by fluids infusion requiring vasopressor). blood samples were collected up to h after the development of first organ dysfunction (d ) and on the th day after inclusion in the study (d ) results: ninety-five patients were enrolled, with median age years (interquatile? - ), apache ii: median ( - ), sofa: median ( - ); . % were admitted in icu with sepsis and . % with septic shock. hospital mortality was . %. in d , nt-probnp correlated with il- (r = . , p < . ) and il- (r = . , p < . ). in d , hs-ctnt and nt-probnp correlated with pct (r = . , p < . and r = . , p < . ; respectively). nt-probnp d was higher in nonsurvivors than in survivors on mortality in seventh day (p = . ) and in-hospital mortality (p = . ). hs-ctnt d (p = . ) and nt-probnp d (p < . ) were significantly higher in non-survivors on in-hospital mortality. nt-probnp d (or . ; ic % . - . , p= , ) and hs-ctnt d (or , ; ic % . - . , p= , ) were independently associated with in-hospital mortality conclusions: nt-probnp plasma levels at d correlated with il- and il- , and both nt-probnp and hs-ctnt at d correlated with pct. in addition, nt-probnp has been shown to be an important predictor of mortality introduction: heparin-binding protein (hbp) acts proinflammatory on immune cells and induces vascular leakage through cytoskeletal rearrangement and cell contraction in the endothelium and is a promising novel prognostic biomarker in sepsis and septic shock. however, studies on repeated measures of hbp are lacking. our objective was to describe the kinetics of plasma hbp during septic shock and correlate it to hemodynamic parameters. methods: we included patients with septic shock (sepsis- ) on admission to helsingborg hospital's intensive care unit (icu) during september to february . patients were sampled from icu admission and every hours for hours or until death or icu discharge. the plasma samples were analyzed for hbp and converted using the natural log (lnhbp) for normality. lnhbp was then evaluated against mean arterial pressure (map) as primary analysis and against systemic vascular resistance index (svri) as a secondary analysis, using mixed-effects linear regression models, treating patient id as a random intercept and adjusting for hemodynamic parameters. results: a total of patients were included with median age years, females ( %), surgical admissions ( %), median sofa-score points on day one and deaths from all causes within days ( %). plasma hbp ranged from to ng/ml with a median of ng/ml (lnhbp range . to . , median: . ). an increase lnhbp was significantly associated with a decrease in map (coef. - . mmhg, % ci: - . to - . , p= . , n= ), when adjusting for heart rate (hr), noradrenaline (na), vasopressin (vp), dobutamine (dbt) and levosimendan (ls). in a secondary subgroup analysis, an increase in lnhbp was also significantly associated with a decrease in svri (coef. - . dyne*s*cm- *m- , % ci: - . to - . , p= . , n= ), when adjusting for map, hr, na, vp, dbt, ls and cardiac index. conclusions: repeated measures of plasma hbp during septic shock were correlated with important hemodynamic parameters in this small pilot study. introduction: mid-regional pro-adrenomedullin (mr-proadm) comes from the synthesis of the hormone adrenomedullin (adm), which is overexpressed during inflammation and progression from sepsis to septic shock. thus, mr-proadm can be a useful biomarker for the clinical management of septic patients [ ] . the aim of our study was to understand the ability of mr-proadm to predict -day ( -d) mortality and to find a correlation between mr-proadm and sequential organ failure assessment (sofa) score in the first hours from intensive care unit (icu) admission. methods: we evaluated consecutive septic shock patients according to sepsis iii definitions. clinical data from the medical records included demographics, comorbidities, laboratories, microbiology and biomarker levels. whole blood samples for biomarker profiling were collected at , and hours from icu admission. mr-proadm measurement was detected in edta plasma using a sandwich immunoassay by trace® (time resolved amplified cryptate emission) technology (kryptor thermo fischer scientific brahms). results: overall -d mortality rate was . %. mr-proadm [odds ratio (or) = . ], sofa score (or = . ) and lactate (lac) levels (or = . ) in the first hours were associated with -d mortality in univariate logistic analysis (p value < . , table ). -d mortality rate was not associated with procalcitonin (pct) levels (or = . ). further linear regression analysis showed significant correlation between mr-proadm and sofa score at hours from icu admission (p value< . , fig. , table ). conclusions: mr-proadm demonstrated superior accuracy to predict -d mortality compared to pct levels and is directly linked to sofa score at hours from admission. mr-proadm may aid early identification of poor prognosis septic patients who could benefit a more intensive management. introduction: study of the expression of cell free dna (cfdna) in the search for new biomarkers for infection, sepsis and septic shock. methods: the population studied was all patients included in the sepsis protocol from march to january , hospitalized patients of a federal public hospital. plasma samples were collected for quantification of cfdna, which after centrifugation were stored at - °c and then thawed and analyzed by fluorescence using a varioskan flash fluorometer). cfdna values were expressed as ng/ml. the patients were divided into groups: infection and sepsis/septic shock. we analyzed mortality, sequential organ failure assessment score (sofa score), qsofa (quick sofa), comorbidities, cfdna and laboratory parameters of patients. results: among the patients, % were classified as infection and % sepsis/septic shock. overall lethality was %, infection . %, and sepsis/septic shock . % (p< . ). the mean of cfdna, sofa and lactate was higher according to the classification of infection and sepsis/septic shock: cfdna ( . ± . and . ± . , p= . ), sofa ( . ± . and . ± . , p< . ), qsofa (positive in % and %, lactate ( . ± . and . ± . , p< . ). we analyzed leukocytes, creatinine, crp (c reactive protein), inr (international normalized ratio), as predictors of severity and only crp showed no association with disease severity (p= . ). levels of cfdna and qsofa showed worse prognostic utility as a predictor of sepsis / septic shock when compared to lactate and sofa: or . ( % ci . - . ), p= . for cfdna, or . ( % ci . - . ), p= . for sofa and or . ( % ci . - . ), p= . for lactate. negelkerke r square was , for cfdna. in addition, area under the curve for cfdna mortality was . ( % ci . - . ) and sofa . ci % . - . ). conclusions: our study suggests that cfdna and qsofa have worse prognostic accuracy when compared to lactate and sofa, variables already used in clinical practice and easily measured. introduction: the aim of this study is to develop a "molecular equivalent" to sequential organ failure assessment (sofa) score, which could identify organ failure in an easier, faster and more objective manner, based on the evaluation of lipocalin- (lcn /ngal) expression levels by using droplet digital pcr (ddpcr). sepsis has been classically defined as the exuberant, harmful, pro-inflammatory response to infection. this concept is changing [ ] and the presence of a life-threatening organ dysfunction caused by a dysregulated host response to infection is now considered a central event in the pathogenesis of sepsis [ ] . methods: lcn expression levels were quantified by ddpcr in blood of a total of surgical patients with a diagnosis of infection. spearman analysis was used to evaluate if lcn correlated in a significant manner with sofa score. area under the receiver operating curve (auroc) analysis and multivariate regression analysis were employed to test the ability of lcn to identify organ failure and mortality risk. results: spearman analysis showed that there was a positive, significant correlation between lcn expression levels and sofa score (fig. ) . aurocs analysis showed that lcn presents a good diagnostic accuracy to detect organ failure and mortality risk (fig ) . in the multivariate regression analysis, patients showing lcn expression levels over the optimal operating points (oops) identified in the aurocs showed a higher risk of developing organ failure (table ) and a higher mortality risk (table ) . conclusions: quantifying lcn expression levels by ddpcr is a promising approach to improve organ failure detection and mortality risk in surgical patients with infection. introduction: sepsis is an inflammatory state due to an exacerbated immune response against infection. in cancer patients, sepsis presents a -fold higher mortality than in general population and leads to longer intensive care unit (icu) and hospital lengths of stay. it has been shown that reduced levels of circulating immunoglobulins (ig) might be a surrogate marker of unfavorable outcome in sepsis [ ] . the aim of this study was to evaluate the association between ig levels in plasma and -day mortality rate in cancer patients with septic shock. methods: from december to november , we conducted a prospective study in the intensive care unit (icu) of cancer institute of state of sao paulo, an -bed icu linked to university of sao paulo. patients ≥ years old with cancer and septic shock were enrolled. descriptive statistics were computed for demographic and outcome variables. laboratory data and ig levels were collected at icu admission and at days , and . a multivariate analysis was performed to evaluate predictors of -day mortality. results: a total of patients were included in the study. the -day and -day mortality were . % and . %, respectively. no significant differences in igm and igg levels were observed between survivors and non-survivors. in both groups, the median igm levels were low and the median igg levels were normal. in the multivariate analysis for -day mortality, a favorable status performance measured by the eastern cooperative oncology group (ecog) was associated with better survival; metastatic disease, higher sequential organ failure assessment (sofa) score at admission and higher levels of initial lactate were associated with increased mortality. conclusions: low levels of serum endogenous immunoglobulins are not predictors of -day mortality in cancer patients with septic shock. introduction: cytovale has developed a rapid biophysical assay of the host immune response which can serve as a rapid and reliable indicator of sepsis. neutrophils and monocytes undergo characteristic structural and morphologic changes in response to infection. one type of response is the generation of neutrophil extracellular traps (nets), these have been proposed as potential mediators for widespread tissue damage. during netosis there is a fundamental reorganization of a cell's chromatin structurea signal that we have shown is sensitively measured by the cytovale cytometer. we hypothesized that quantification of plasticity (deformability) of leukocytes in the peripheral blood provides an early indicator of sepsis. the cytovale assay uses microfluidic cytometry to measure the plasticity of up to , white blood cells from edta-anticoagulated, peripherally-collected whole blood and provides a result in minutes. methods: in two prospective studies conducted in two academic medical centers in baton rouge, la, the cytovale test was performed on peripheral blood samples obtained from patients who presented to the emergency department with signs or symptoms suggestive of infection. the two studies included high acuity patients ( patient study) and low acuity patients ( patient study). an adjudicated reference diagnosis of sepsis or no sepsis was established for each subject, using consensus definitions, by review of the complete medical records. results: the receiver operator curve (roc) performance of the cytovale assay for both studies demonstrated an area under the curve (auc) greater than . (fig. ) . conclusions: measurement of neutrophil and monocyte plasticity by a novel assay provides an accurate and rapid indication of sepsis in patients who present to an emergency room with signs or symptoms of infection. plasma hepatocyte growth factor in sepsis and its association with mortality: a prospective observational study introduction: sepsis and septic shock are commonly associated with endothelial cell injury. hepatocyte growth factor (hgf) is a multifunctional protein involved in endothelial cell injury and plays a pivotal role in sepsis. this study assesses its correlation with relevant endothelial cell injury parameters and prognostic value in patients with sepsis. methods: a prospective, observational cohort study was conducted in patients with sepsis admitted to the department of critical care medicine at the zhongda hospital from november to march . the plasma hgf level was collected on the first h after admission (day ) and day , then was measured by enzyme-linked immunosorbent assay. the primary endpoint was defined as all-cause -day mortality. furthermore, we analyzed the correlation of hgf with relevant endothelial cell injury markers. results: eighty-six patients admitted with sepsis were included. hgf levels of non-survivors were elevated upon day ( . ± . pg/ml vs. . ± . pg/ml; p = . ) and day ( . ± . pg/ml vs. . ± . pg/ml; p = . ) compared with that in survivors, and showed a strong correlation with von willebrand factor (r = . , p < . ), lactate (r = . , p = . ), pulmonary vascular permeability index (r = . , p = . ), first h fluid administration (r = . , p < . ) and sequential organ failure assessment score (r = . , p = . ) (fig. ) . plasma levels were able to discriminate prognostic significantly on day (auc: . , %ci: . - . ) and day (auc: . , %ci: . - . ) (fig. ) . conclusions: hgf levels are associated with sepsis and are correlated with established markers of endothelial cell injury. elevated hgf level in sepsis patients is a predictor of mortality. methods: adult patients with septic shock by the sepsis- classification due to lung infection or primary bacteremia or acute cholangitis are screened using two consecutive measurements of ferritin and of hla-dr/cd co-expression for mals (ferritin above , ng/ml) or immunosuppression (hla-dr/cd less than %) and randomized into immunotherapy with either anakinra (targeting mals) or recombinant ifnγ (targeting immunosuppression) and into placebo treatment. main exclusion criteria are primary and secondary immunodeficiencies and solid and hematologic malignancies. results: patients have been screened so far. most common infections are community-acquired pneumonia ( . %), hospitalacquired pneumonia ( . %) and primary bacteremia ( . %). mean +/-sd sofa score is . +/- . and charlson's comorbidity index . +/- . ; patients have mals ( . %); two immunosuppression ( %); the majority remain unclassified for immune state. conclusions: current screening suggests greater frequency of mals than recognized so far in a setting of septic shock due to lung infection or primary bacteremia or acute cholangitis. development of an algorithm to predict mortality in patients with sepsis and coagulopathy d hoppensteadt , a walborn , m rondina , j fareed study was to develop an equation incorporating biomarker levels at icu admission to predict mortality in patients with sepsis, to test the hypothesis that using a combination of biomarkers of multiple systems would improve predictive value. methods: plasma samples were collected from patients with sepsis at the time of icu admission. biomarker levels were measured using commercially available, elisa methods. clinical data, including the isth dic score, sofa score, and apache ii score were also collected. -day mortality was used as the primary endpoint. stepwise linear regression modeling was performed to generate a predictive equation for mortality. results: differences in biomarker levels between survivors were quantified and using the mann-whitney test and the area under the receiver operating curve (auc) was used to describe predictive ability. significant differences (p< . ) were observed between survivors and non-survivors for pai- (auc= . ), procalcitonin (auc= . ), hmgb- (auc= . ), il- (auc= . ), il- (auc= . ), protein c (auc= . ), angiopoietin- (auc= . ), endocan (auc= . ), and platelet factor (auc= . ). a predictive equation for mortality was generated using stepwise linear regression modeling. this model incorporated procalcitonin, vegf, the il- :il- ratio, endocan, and pf , and demonstrated a better predictive value for patient outcome than any individual biomarker (auc= . ). conclusions: the use of a mathematical modeling approach resulted in the development of a predictive equation for sepsis-associated mortality with performance than any individual biomarker or clinical scoring system. furthermore, this equation incorporated biomarkers representative of multiple physiological systems that are involved in the pathogenesis of sepsis. the effects of biomarker clearances as markers of improvement of severity in abdominal septic shock during blood purification t taniguchi , k sato , m okajima introduction: sepsis associated coagulopathy (sac) is commonly seen in patients which leads to dysfunctional hemostasis. the purpose of this study is to determine the thrombin generation potential of baseline blood samples obtained from sac patients and demonstrate their relevance to thrombin generation markers. methods: baseline citrated blood samples were prospectively collected from patients with sac at the university of utah clinic. citrated normal controls (n= ) were obtained from george king biomedical (overland park, ks). thrombin generation studies were carried out using a flourogenic substrate method. tat and f . were measured using elisa methods (seimens, indianapolis, in). functional antithrombin levels were measured using a chromogenic substrate method. results: the peak thrombin levels were lower ( ± nm) in the dic patients in comparison to higher levels observed in the normal plasma ( ± nm). the auc was lower ( ± ) in the dic group in comparison to the normals ( ± ). the dic group showed much longer lag time ( . ± . ) in comparison to the normal group ( . ± . ). wide variations in the results were observed in these parameters in the dic group. the f . levels in the dic group were much higher ( ± pmol) in comparison to the normal ( ± pmol). the tat levels also increased in the dic group ( . ± . ng/ml) in comparison to the normal ( . ± . ng/ml). the functional antithrombin levels were decreased in the dic group ( ± %). conclusions: these results validate that thrombin generation such as f . and tat are elevated in patients with dic. however thrombin generation parameters are significantly decreased in this group in comparison to normals. this may be due to the consumption of prothrombin due to the activation of the coagulation system. the decreased functional at levels observed in the dic group are due to the formation of the complex between generated thrombin and antithrombin. introduction: sepsis-associated disseminated intravascular coagulation (dic) is a complex clinical scenario involving derangement of many processes, including hemostasis. assessment of markers including inflammation, endothelial function, and endogenous anticoagulants may provide insight into dic pathophysiology and lead to improved methods for assessment of patient condition and response to treatment. methods: citrated plasma samples were collected from patients with sepsis and suspected dic at icu admission and on days and . dic score was determined using the isth scoring algorithm (e.g. platelet count, pt/inr, fibrinogen and d-dimer). cd ligand (cd l), plasminogen inhibitor (pai- ), nucleosomes, procalcitonin (pct), microparticle tissue factor (mp-tf) and prothrombin . (f . ) were measured using commercially available elisa kits. protein c activity was measured using a clot-based assay. interleukin (il- ), interleukin (il- ), interleukin (il- ), tumor necrosis factor alpha (tnfα), and monocyte chemoattractant protein (mcp- ) were measured using biochip technology. results: significant differences in levels of protein c (p= . ), pct (p= . ), il- (p= . ), il- (p= . ), pai- (p= . ), were observed between survivors and non-survivors. significant variation of protein c (p= . ), nucleosomes (p= . ), pct (p< . ), il- (p= . ), il- (p= . ), il- (p= . ), tnfα (p= . ) and mcp- (p= . ) were observed based on severity of dic score. conclusions: markers from multiple systems perturbed in dic were associated with mortality, suggesting that while these systems may not be routinely evaluated in the normal course of patient care, dysfunction of these systems contributes significantly to mortality. in addition, numerous inflammatory cytokines showed an association with dic score. this suggests that the measurement of additional markers in sepsis-associated dic may be of value in the prediction of mortality and may be helpful in guiding treatment for these patients. introduction: the endotoxin activity assay (eaa) is a rapid immunodiagnostic test based on chemiluminescence. it was approved by the fda in as a diagnostic reagent for risk assessment of severe sepsis in the icu. ascertaining endotoxin levels in the bloodstream is important in targeting patients and determining the appropriate timing for initiation of treatment. it has high sensitivity and specificity for endotoxin, and is considered to be useful in predicting clinical symptoms and determining prognosis. the usefulness of the eaa has yet to be fully clarified. methods: a total of patients admitted to the icu between january and june with suspected sepsis or sepsis were enrolled. the eaa was conducted within hr after admission. patient characteristics were determined, together with levels of il- , procalcitonin, presepsin, and pao /fio . thereafter, the patients were classified into groups depending on their eaa value: ) < . ; ) from ≤ . to < . ; ) from ≤ . to < . ; ) from ≤ . to < . ; and ) ≤ . ). the transition of various markers was also examined. the spearman rank correlation, wilcoxon rank sum test, and a nonrepeated anova were used for the statistical analysis. a p-value of < . was considered statistically significant. the eaa values showed a positive correlation with both the apache ii (r= . ) and sofa scores (r= . )(p< . ), although that with the latter was stronger. a significant correlation was also observed with levels of procalcitonin (r= . ) and presepsin (r= . early diagnosis is important to allow early intervention. the current clinical methods are insufficient for early detection. we hypothesized that intraperitoneal microdialysis allows detection of peritonitis prior to changes in standard clinical parameters in a pig model. methods: bacterial peritonitis was induced in pigs by bowel perforation and intraperitoneal fecal instillation, one pig underwent sham surgery. intraperitoneal microdialysis catheters were placed in each abdominal quadrant. the observation time was hours. results: in peritonitis pigs the intraperitoneal lactate increased during the first two hours and remained elevated throughout the observation time (table ) , whereas the arterial lactate remained within reference range (< . mm). intraperitoneal glucose decreased significantly. hemodynamics were hardly influenced during the first two hours, and decreased thereafter. sham surgery did not influence in any of the parameters. conclusions: a rapid and pronounced increase in intraperitoneal lactate and decrease in intraperitoneal glucose was observed after instillation of intraabdominal feces. systemic lactate increase was absent, and the hemodynamic response was delayed. postoperative intraperitoneal microdialysis is applicable in detecting peritonitis earlier than standard clinical monitoring and should be evaluated in a clinical study in order to explore if early intervention based on md data will reduce icu length of stay, morbidity and mortality. introduction: procalcitonin (pct) is a serum biomarker suggested by the surviving sepsis campaign to aid in determination of the appropriate duration of therapy in septic patients. trauma patients have a high prevalence of septic complications, often difficult to distinguish from inflammatory response. pct values typically declined after h from trauma and increased only during secondary systemic bacterial infections. the aims of the study are to evaluate reliability and usefulness of pct serum concentration in trauma. methods: we retrospectively analyzed data from trauma patients admitted to icu at bufalini hospital -cesena, from july to august . we collected data about antimicrobial therapy, injury severity score (iss), first arterial lactate in emergency room, sofa score and sepsis severity. plasma pct concentration was measured using an automate analyzer (modular e-brahms) on st day of antimicrobial therapy and every h hours. antimicrobial therapy was stopped according to a local protocol; however medical judgment was considered the overriding point for therapeutic decision. results: median iss of patients was . , inter quartile range (iqr) . . pct mean concentration at the starting of antimicrobial treatment was . μg/l (d.s . ), median . (iqr . ). no significative correlation (spearman´s rho test) was found between pct at day of antimicrobial therapy and iss (rho - . ), between first arterial lactate in er and pct (rho . ). daily course of pct was not related to distance from trauma (rho - . ). in of patients ( . %) pct measurement led physician to save days of antimicrobial therapy compared with standard clinical practice. we couldn´t find any cut off value. conclusions: our experience suggests that pct could help physician to optimize duration of antimicrobial therapy in trauma patients. no standard approach can be recommended at present. introduction: long duration of antimicrobial treatment may predispose to colonization and subsequent infections by multidrugresistant organisms (mdro) and clostridium difficile. progress (clinicaltrials.gov registration nct ) is an on-going trial aiming to use pct for the restraining of this calamity. methods: adult patients with sepsis by the sepsis- classification and any of five infections (pneumonia community-acquired; hospital-acquired or ventilator-associated; acute pyelonephritis; primary bacteremia) are randomized to pct-guided treatment or standard of care (soc) treatment. in the pct arm antibiotics are discontinued when pct on or after day is decreased by more than % of the baseline or remains below . ng/ml; in the soc arm antibiotics are discontinued at the discretion of the attending physician. patients are followed for six months. primary endpoint is the rate of infections by mdro and/or c.difficile or death. serial stool samples are cultured for mdro and screened for glutamate dehydrogenase antigen and toxins of c.difficile. results: patients have been enrolled so far. mean ± sd sofa score is . ± . . most common diagnoses are community-acquired the progress trial is the first trial assessing the probable benefit from pct guidance to reduce ecological sequelae from long-term antibiotic exposure. analysis of baseline patient characteristics indicates that progress is a real-world trial so that results can have major clinical impact. prospective multi-site validation of -gene host response signature for influenza diagnosis s thair , s schaffert , m shojaei , t sweeney there are no blood-based diagnostics able to identify influenza infection and distinguish it from other infections. we have previously described a blood-based -gene influenza meta-signature (ims) score to differentiate influenza from bacterial and other viral respiratory infections. methods: we prospectively validated the ims in a multi-site validation study by recruiting individuals ( patients with suspected influenza, healthy controls) in community or hospital clinics across australia. we assayed the ims and genes from viral genome of influenza strains to generate the blood flu score (bfs) as a measure of viremia using nanostring from whole blood rna. results: using clinically determined phenotypes, the ims score distinguished patients with influenza from healthy (auc= . ), non-infected (auc= . ), bacterial (auc= . ), other viruses (auc= . ) ( figure a) . interestingly, probes of bfs were found in all phenotypic groups (non-infected, bacterial, and other viral infections) to varying degrees, and positively correlate with the ims score (r= . ). ims aurocs improve when the bfs is used to inform the phenotypic groups: healthy (auc= . ), non-infected (auc= . ), bacterial (auc= . ), other viruses (auc= . ) ( figure b ). patients who were clinically influenza negative but had a high ims and bfs were admitted less often, yet had~ -fold higher mortality than those who were clinically influenza negative with low ims and no bfs (table ) . conclusions: collectively, our prospective multi-center validation of the ims demonstrates its potential in diagnosis of influenza infections. introduction: previous findings of our group suggest that patients with gram-negative hospital-acquired severe sepsis have better prognosis when sepsis is developing after recent multiple trauma through stimulation of favorable interleukin (il)- responses [ ] . under a similar rationale, we investigated if preceding osteomyelitis may affect experimental osteomyelitis. methods: sham or experimental osteomyelitis was induced in male new zealand white rabbits after drilling a hole at the upper metaphysis of the left tibia and implementing diluent or log of staphylococcus aureus using foreign body. after three weeks, the foreign body was removed and experimental pyelonephritis or sham surgery was induced after ligation of the right pelvo-ureteral junction and instillation of log of escherichia coli in the renal pelvis. survival was recorded and circulating mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (tnfa) and il- . at death or sacrifice, tissue outgrowth and myeloperoxidase (mpo) were measured. results: four sham-operated rabbits (s), rabbits subject to sham surgery and then pyelonephritis (sp) and rabbits subject to osteomyelitis and then pyelonephritis (op) were studied. survival after days of group sp was . % and of group op % (log-rank . ; p: . ). lab findings are shown in figure . il- production was blunted. negative correlation between e. coli outgrowth and tissue mpo was found at the right kidney of the op group (rs: - . , p: . ) but not of the sp group (rs: - . , p: . ). conclusions: preceding staphylococcal osteomyelitis provides survival benefit to subsequent experimental osteomyelitis through downregulation of innate immune responses leading to efficient phagocytosis. introduction: activation of neutrophils is a mandatory step and a sensitive marker of a systemic inflammatory response syndrome (sirs) which is closely related to development of multiple organ failure. the search for drugs that can prevent sirs and reduce mortality in critically ill patients remains significant. the aim of this study was to study the anti-inflammatory effect of the synthetic analogue of leu-enkephalin (dalargin) on human neutrophils. methods: the study was conducted on isolated from the blood of healthy donors neutrophils. their activation was assessed by fluorescent antibodies to markers of degranulation cd b and cd b (sd b-fitc and cd b-alexafluor (bd biosciences, usa). as inductors of inflammation lipopolysaccharide (lps) and the peptide formyl met-leu-pro (fmlp) were used. mkm fmlp and dalargin in concentrations of and μ g / ml were added to neutrophils at a concentration of ppm / ml and incubated for min at °c; then antibodies were added and incubated for min on ice; then fluorescence was assessed by flow cyto flow meter beckman-coulter fc . non-parametric criteria were used; data were presented as a median and %- % interquartile intervals. the statistical significance was estimated using mann-whitney test. the difference was considered statistically significant at p< . results: synthetic analogue of leu-enkephalin in various concentrations has an anti-inflammatory effect on both intact and preactivated with bacterial components neutrophils, reducing their activation and degranulation in a dose-dependent manner (figs. , ) . conclusions: synthetic analogue of leu-enkephalin prevents neutrophil activation by bacterial compounds. this has a potential of translation into clinical practice for sepsis treatment. introduction: the endothelin system plays important roles in circulatory regulation through vasoconstrictor et-a and et-b receptors and vasodilator et-b receptors (etar; etbr, respectively). tissue hypoxia during the progression of sepsis is associated with microcirculatory and mitochondrial disturbances. our aim was to investigate the possible influence of etar antagonist, etbr agonist or combined treatments on oxygen dynamics, microcirculatory and mitochondrial respiration parameters in experimental sepsis. methods: male sprague-dawley rats (n= /group) were subjected to faecal peritonitis ( . g/kg faeces ip) or sham-operation. septic animals were treated with sterile saline solution, or received the etar antagonist etr-p /fl peptide ( nmol/kg iv), etbr agonist irl- ( . nmol/kg iv) or same doses as combination therapy, hr after sepsis induction. invasive hemodynamic monitoring and blood gas analyses were performed during a -min observational window. introduction: sepsis often induces immunosuppression, which is associated with high mortality rates. nivolumab is a human igg- antibody directed against the programmed cell death (pd- ) immunecheckpoint inhibitor, which disrupts pd- -mediated signaling and restores antitumor immunity. nivolumab is an approved anti-cancer drug that may have the potential to improve sepsis-induced immunosuppression. methods: this multicenter, open-label study investigated the safety, pharmacokinetics and pharmacodynamics of a single intravenous infusion of or mg nivolumab in japanese patients with immunosuppressive sepsis (lymphocytes ≤ /μl). the dosing of nivolumab was set using the predicted steady state concentration of nivolumab at mg/kg every weeks (q w), which was the approved dosage for cancer patients at the time of planning. results: five and eight patients were assigned to the and mg groups, respectively. the mean (standard deviation) peak serum drug concentration in the mg group was comparable to the predicted median concentration ( % pi [prediction (figures and ). adverse events (aes) were observed in four patients in each group. drug related-aes were observed in only one patient in the mg group (table ) . no deaths related to nivolumab occurred. conclusions: a single dose of mg nivolumab appeared to be well tolerated and sufficient to maintain nivolumab blood concentration in patients with sepsis. results suggest both and mg nivolumab therapy could improve relevant immune indices. introduction: the systemic inflammatory response syndrome (sirs) accompanies tissue trauma and infection and, when severe or dysregulated, contributes to multiple organ failure and critical illness. observational studies in man and animal have shown that low-dose acetyl-salicylic acid promotes resolution of inflammation and might attenuate excessive inflammation by increasing the synthesis of specialised pro-resolving lipid mediators (spms). methods: we randomly assigned patients with sirs who were expected to stay in icu for more than hours to receive enteral aspirin ( mg per day) or placebo for days or until death or discharge from the icu, whichever came first. the primary outcome was il- serum concentration at h after randomisation. the secondary outcomes included safety and feasibility outcomes. in one center, additional blood samples were taken during the first three days for exploratory analysis of spms using reversed-phase highperformance liquid chromatography -tandem mass spectrometry (rp-hplc-ms/ms). results: from march through december a total of patients across four general icus in australia underwent randomization (table ) . compared to placebo patients, il- serum concentration after h in aspirin-treated patients was not significantly lower ( [ - ] pg/ml vs [ . - ] pg/ml; p= . ). there were no significant differences for control vs. aspirin-treated patients in the change of pro-resolving/anti-inflammatory lipids between the time points (figure , ). there were no between-group differences with respect to icu or hospital mortality, number of bleeding episodes or requirements for red cell transfusions (table ) . conclusions: in patients admitted to the icu with sirs, low-dose aspirin did not result in a decreased concentration of inflammatory biomarkers compared with placebo. introduction: sepsis is associated with excessive ros production, nf-kb, inos and inflammatory mediators overexpression. vitamin c is a cellular antioxidant, it increases enos and decreases nf-kb; it has several immune-enhancing effects and is crucial for endogenous vasopressors synthesis. vitamin c reserves in sepsis are often as poor as in scurvy [ ] . in recent studies, intravenous high vitamin c dose seems to reduce organ failure and improve outcome in septic shock. methods: we treated all septic shock patients admitted to our icu in months (from / to / ) with intravenous vitamin c . g/ h and thiamine mg/ h (for its synergistic effects) [ ] as adjunctive therapy for consecutive days and we compared data to septic shock patients admitted in the previous months period. we enrolled patients: received vitamins supplementation, standard of care. we analysed -days mortality, sofa at and hours, pct variation from baseline in first days, vasoactive therapy length and daf (days alive and free from vasopressors, mechanical ventilation and rrt in days follow up). patients with end stage kidney disease were ruled out. we analysed data with mann-whitney and wilcoxon tests. results: vit c group showed lower -days mortality ( % vs . %: ns); sofa improvement at (- . ± . vs - . ± . : p= . ) and hours (- . ± vs - . ± : p< . ) was higher in vit c group; vit c patients had faster pct reduction without statistical significance. mean vasoactive therapy length was quite similar. daf was . (± . ) days in vit c group and . (± . ) in controls (p= . ). control patients needed rrt, none in vit c group. conclusions: despite small study size, we found that vit c has positive effects on survival and improves sofa score (fig. ) and daf (fig. ) in septic shock. no vit c patient developed oxalate nephropathy nor worsened renal function. introduction: toxin-producing gram-positive organisms cause some of the most severe forms of septic shock [ , ] . adjunctive therapies such as intravenous immunoglobulins (ivig) have been proposed for these patients [ , ] . however, at patient presentation, the presence of a toxin-producing organism is most often unknown. methods: we reviewed the use of ivig in our patients requiring extracorporeal membrane oxygenation (ecmo) in a -year period between february and march . results: in % ( / ) of the patients that received ivig for presumed toxin-mediated shock, group a streptococcus or panton-valentine leukocidin producing s. aureus was isolated, but the clinical characteristics of these patients were not significantly different from the ones with other final diagnoses, except for a predisposing influenza infection and the presence of an often very high procalcitonin level. these patients were extremely unwell at presentation with a sofa score of ± , high lactate levels ( . ± . mmol/l) and need for vasopressors (equivalent norepinephrine dose of . ± . μ g/kg/min). they had very high inflammatory parameters with a procalcitonin ≥ ng/ml in more than half of patients ( / ). ivig use in these patients was generally safe, with only possible transfusion reaction. the mortality of % ( / ) was lower than predicted based on the sofa scores. conclusions: ivig administration can be considered in a selected group of patients presenting with acute and very severe septic shock, as part of a multimodal approach [ ] . introduction: extra corporeal treatments are used in septic patients to decrease the inflammatory mediators, but definitive conclusions are lacking . more over in many studies the effect of aki isn't evaluated and this may be an important bias. . the aim of this study is to evaluate in septic patients with aki: the effect of the adsorbing membrane oxiris on the immunological response -the different response in survivors and non survivors methods: from our local data base we analyzed retrospectively septic shock patients with aki (kdigo classification) submitted to crrt with the adsorbing membrane oxiris (baxter, usa ) . at basal time ( t ) and at the end of the treatment ( t ) we evaluated the following variables: il il procalcitonin endotoxin (eaa). all data are expressed as mean ±sd or median and iqr. student t test or mann-whitney was used to compare values changes. p < . was considered statistically significant. results: thirty patients with sepsis /septic shock and aki were enrolled in this study. patients had aki , patients aki , patients aki . the duration of treatment was ± hours. patients had citrate as anticoagulation and heparine continous ev. at table are shown the main results of this study in all the patients. survivors vs non survivors had a significant decrease of il , procalcitonin and eaa. conclusions: data of this study confirm on clinical ground previous study "in vitro" [ ] that the adsorbing membrane oxiris has important immunological effect during septic shock with aki. this must be confirmed in a rct. introduction: sepsis is common and often fatal, representing a major public health problem. hemoadsorption (cytosorb) therapy aims to reduce cytokines and stabilise the overall immune response in septic shock patients. methods: a prospective, multi-centre, investigator initiated study to evaluate hemoadsorption (cytosorb) therapy in septic shock patients admitted to a tertiary icu's in india during to . all centres followed a common protocol and received ethics committee approval. results: a total of patients were administered cytosorb in addition to standard of care. a total of patients ( %) survived out of patients. among survival group, patients ( %) were administered cytosorb within hours of icu admission resulting in significant reduction in sepsis scores, apache ii ( . vs . ) and sofa ( . vs . ) post cytosorb therapy. also there was reduction in inflammatory markers like cytokines il in most of the patients. all patients in survivor group showed a significant improvement in map ( . vs . ) and reduction in vasopressors (epinephrine . to . mcg/kg/min, nor-epinephrine . to . mcg/kg/min) after cytosorb therapy. no device related adverse effect was observed in any of the patients. among the non-survivor group, ( patients, %) we observed that cytosorb was administered after hours of icu admission. although a few patients showed improvement in sofa score, majority did not show a significant improvement with map ( . vs . mm of hg) and required increased demand in vasopressors. conclusions: in this multi-centered prospective iis study, we could observe clinical benefits of hemoadsorption (cytosorb) therapy in septic shock patients if the therapy was initiated early. larger randomised study are required to establish the above clinical benefits in larger patient population. a single centre experience with hemoadsorption (cytosorb) in varied causes of sepsis and mods y mehta , c mehta , a kumar , j george , a gupta , s nanda , g kochar , a raizada introduction: sepsis and the multiorgan failure is a leading cause of mortality in the intensive care unit. promising new therapies continue to be investigated for the management of septic shock. we tried to evaluate a novel hemoadsorption therapy (cytosorb) through a retrospective evaluation of patient's data in our centre. we used it as an adjuvant therapy in our patients with sepsis due to varied causes. methods: we retrospectively analysed data of introduction: septic shock is a life-threatening multiple organ dysfunction that has high morbidity and mortality in critically ill patients, due to a dysregulated host response to infection. the aim of this study was to evaluate the efficacy of therapeutic cytokine removal (cytosorb®) in the management of patients with septic shock. methods: we retrospectively analyzed patients admitted to icu with septic shock between june and november . patients included in the study were diagnosed according to the third international consensus definitions for sepsis and septic shock (sepsis- ), received maximal supportive care including continuous veno-venous hemodiafiltration (cvvhdf) for acute kidney injury and cytosorb® haemoadsorption column was added to return limb of the cvvhdf circuit. demographic data, procalcitonin and leukocyte levels before and after therapeutic cytokine removal and duration of cytosorb® haemoadsorption column application and apache ii scores were recorded. results: the mean age of patients included in the study was ± . years ( % male) and the mean body mass index was . ± . . the mean apache ii score was . with an expected and actual mortality rates of % and %, respectively. % of the patients were admitted with sepsis and % of them with septic shock. . % (n= ) of the cases were solid organ transplant recipients. cvvhdf was applied in all patients during therapeutic cytokine removal. treatment was combined with ecmo in patients. while the mean duration of cvvhdf was . hours, the duration of cytosorb® haemoadsorption column application was . ± . hours. procalcitonin ( . ± ng/ml vs ± ng/ml) and leucocyte levels ( ± / mm vs ± mm ) after therapeutic cytokine removal were found significantly lower than the pretreatment values (respectively p= . , p= . ). conclusions: therapeutic cytokine removal applied with cvvhdf in septic shock patients have positive contributions to biochemical parameters and provide survival advantage. introduction: recent studies have focused on demonstrating the potential benefits of immunomodulation in the management of septic patients. the aim of our study was to assess the effects of a hemoadsorption column (cytosorb®) in critical ill septic patients. methods: after ethical approval was obtained, we prospectively included patients admitted to the general icu of fundeni clinical institute. three consecutive sessions of renal replacement therapy (continuous venovenous hemodiafiltration) in combination with cytosorb® were applied after icu admission. clinical (heart rate, arterial pressure, temperature, glasgow coma scale) and paraclinical data (pao , serum bilirubin and creatinine, platelet count, white blood cell count, ph, c-reactive protein and procalcitonine), vasopressor support and need for mechanical ventilation were recorded before and after the three sessions. results: the mean age in the study group was ± years. median number of organ dysfunction at the time of icu admission was [ ] [ ] [ ] [ ] [ ] and the mean sofa score was . ± . . the use of cytosorb® was associated with a non-significant increase in pao /fio ratio from ± to ± (p= , ) and creatinine levels from . ± . to . ± . mg/dl (p= . ). although we observed a non-significant increase in c-reactive protein levels from ± mg/l to ± mg/ l (p= . ), we noted a significant decrease in procalcitonine levels from a median of . [ . , . ] ng/dl to a median of . [ . , . ] ng/dl (p= . ). a significant decrease in platelet count was also noted from ± /mm to ± /mm (p= . ). mean sofa score decreased non-significantly from . ± . to . ± . (p= . ). conclusions: the use of cytosorb was associated with a slight nonsignificant improvement in organ function and a decrease of procalcitonine levels. thrombocytopenia remains one of the most important complications of renal replacement therapy. introduction: circulating cell-free neutrophil extracellular traps (nets) would induce a microcirculatory disturbance of sepsis. the removal of nets remnants from the circulation could reduce nets-dependent tissue injury. to address this issue, we evaluated the effect of hemoperfusion with a polymyxin b cartridge (pmx-dhp; toray, japan), which was originally developed for the treatment in patients with gram-negative bacterial infection, on circulating cell-free nets in patients with septic shock and in phorbol myristate acetate (pma)-stimulated neutrophils obtained from healthy volunteer. methods: ex vivo closed loop hemoperfusion was performed through a circuit formed by connecting the small pmx module to a tube and a peristalsis pump. whole blood from healthy volunteers incubated with or without pma or from septic shock patients were applied to circuit and perfused. blood was collected at , and hr after perfusion. circulating cell-free nets were assessed by myeloperoxidase (mpo)-, neutrophil elastase (ne)-, and cell free (cf)-dna. results: plasma mpo-dna, ne-dna and cf-dna levels were significantly increased at hr after pma stimulation when compared with plasma levels without pma. when either blood from septic shock patients or pma-stimulated neutrophils obtained from volunteers were applied to circuit, circulating mpo-dna, ne-dna and cf-dna were significantly reduced in perfusion with pmx filter than in perfusion without pmx filter at times and hr. conclusions: in the ex vivo experiments, mpo-dna, ne-dna and cf-dna were found to decrease after ex vivo perfusion through pmx filters. selective removal of circulating components of nets may improve the remote organ damage in patients with septic shock. a retrospective study of septic shock patients who were treated with direct hemoperfusion with polymyxin b-immobilized fibers based on the levels of endotoxin activity assay s sekine, h imaizumi, i saiki, a okita, h uchino tokyo medical university, anesthesiology/icu, tokyo, japan critical care , (suppl ):p introduction: the purpose of this study was to evaluate the outcomes for septic shock patients with direct hemoperfusion with polymyxin b-immobilized fibers (pmx-dhp) and endotoxin activity assay (eaa). methods: according to the levels of eaa, patients were classified for three groups (low group (gl); eaa < . , intermediate group (gm); eaa > . or eaa < . , high group (gh); eaa > . ). in order to evaluate the severity of illness, acute physiology and chronic health eva-luationii (apache ii) score, the sequential organ failure assessment (sofa) score, catecholamine index (cai) were recorded. and the presence of pmx-dhp treatments were also recorded. blood samples were obtained to measure eaa levels, inflammatory markers (procalcitonin (pct), c-reactive protein (crp), and white blood cell count (wbc)), serum lactate level as an indicator of tissue hypoxia, and for blood culture. apache ii score, sofa score, cai, inflammatory markers, serum lactate levels (lac) and blood culture results were examined for diagnosis of septic shock and prognosis of -days mortality. each values were also compared to eaa levels. results: septic shock patients were included (gl/ gm/ gh: / / ). in gh, apache ii and sofa score was significantly higher than that in gl (p< . ). eaa levels were significantly increased in gramnegative bacteremia patients compared to the patients with grampositive bacteremia or fungemia. there was no relationship between eaa levels and other inflammation markers, cai, and lac. in gm, days mortality in patient with pmx-dhp treatments was lower than that of without pmx-dhp treatments ( . ( / ) vs . ( / ), p= . ). in gh, -days mortality in patient with pmx-dhp treatments was same as that of without pmx-dhp treatments ( . ( / ) vs . ( / ), p= . ). conclusions: these results of this study suggest pmx-dhp treatment may improve the outcome of septic shock patients with intermediate eaa levels. introduction: numerous inconclusive randomized clinical trials (rcts) in sepsis in the past years suggest a need to re-think trial design to improve resource allocation and facilitate policy adoption decisions. the inclass study (clinicaltrials.gov nct: ) is an ongoing rct evaluating clarithromycin as an immune modulator in high-risk septic patients with clinical and cost-effectiveness outcomes. we aim to compare the original one-shot trial with an alternative sequential design that balances trial costs and value of information. methods: adult patients with sepsis, respiratory failure and total sofa score of at least , are randomized to receive intravenous clarithromycin or placebo adjunctive to standard-of-care therapy. for the cost-effectiveness study, efficacy is measured in quality-adjusted life years (qalys) by eq- d- l questionnaire at days. the endpoint is the incremental net monetary benefit (inmb) of clarithromycin compared to placebo, defined as wtp x (increment in qaly) -(increment in costs), where wtp is willingness to pay per qaly gained. fixed and variable costs of trial execution (including administrative, insurance, supplies, tests) are calculated; hospitalization cost is extracted from patient records; medical care beyond day is recorded; cost of adoption in the general population is estimated. previous data from rcts using clarithromycin are used to form a prior belief about the inmb. known incidence of sepsis with respiratory failure allows estimation of the population to benefit from trial decision. a bayesian model is used to determine the sequential design that maximizes trial value. results: we will compare the performance of the sequential trial design with the one-shot design of inclass trial in terms of sample size, cost, social-welfare, and probability of correctly identifying the best treatment. conclusions: in this protocol we validate a bayesian model for sequential clinical trials and assess the benefits for the patient population and health care system. the effect on the outcome of critically ill patients with catecholamine resistant septic shock and acute renal failure through implementation of adsorption therapy g schittek introduction: cytosorb-adsorption has been described as an effective way for hemodynamic stabilisation in septic shock [ ] . aim of this study was to examine whether the adsorption-therapy could influence patient-outcome with catecholamine resistant septic shock (crss) and acute renal failure(arv). furhtermore we tried to identify clinical constellations that would predict an effective use of adsorbers [ , ] . initial il- in patients with catecholamine-reduction through adsorption was non-significantly different to those with no reduction ( ng/l [ , ] vs. ng/l [ , ]). mortality did not differ significantly between the groups ( % vs %). length of intensive care unit stay (los) did differ significantly ( days [ , ] vs days [ , ] ). conclusions: il- can be reduced with adsorption. patients with catecholamine-reduction did not differ in regard to their initial il- . los was shorter for patients treated with adsorption. according to our experience adsorption can be taken into consideration when crss is beginning. introduction: in our intensive care unit (icu), we have already started expanded application to the contact precautions. applied patients are; ) emergency admission, ) patients who had already had bacteria* that are required to contact precautions, ) scheduled surgical patients with prolonged icu stay, although we have not yet decided the started period of expanded application exactly. *detected bacteria(db);mrsa, cd, mdrp, esbl, pseudomonas a, pisp, prsp, vrsa. the aim of this study was to determine the adequate starting period of expanded application to the contact precautions in the scheduled surgical patients in the mixed icu. methods: we performed retrospective observational study on patients who were admitted to our icu after planed surgery from may to dec. . we detected the patients who acquired bd newly and investigated the relation to the length of icu stay. the relationship between detection rate and categorized date was also analyzed using logistic regression adjusted for age, gender, apache , and sofa score. using youden´s index and roc curve, we also calculated cutoff point of the duration of icu stay related to detection rate. finally, we made the logistic regression model of each cutoff day(day to ) and compared odds ratio(or) and auc of each models using stata. results: category day or more, especially day or more had significantly higher detection rate of db compared to day ( results: pao /fio was lower than mmhg in ( %) patients. compared to patients in group , patients in group were less severely ill at admission but presented a higher sofa and cpis score and a greater incidence of ards and shock at pneumonia onset (fig ) . ( %) patients in group had a microbiological diagnosis of pneumonia, compared to patients ( %) in group (p= . ). pao /fio ≤ mmhg was associated with less probability of having microbiological diagnosis of pneumonia (or . , % ci . to . , p= . ). when adjusted for other variables significantly associated with positive microbiology, pao /fio ≤ mmhg remained significantly associated with less probability of a microbiological diagnosis (adjusted or . , % ci . to . , p= . ). hospital mortality was significantly higher in patients in group compared to group ( % vs %, p= . ). however, no difference was found in non-response to treatment, icu and hospital stay, icu mortality (table ) and -days survival (fig ) . conclusions: a significant higher number of patients with vap didn't have a definitive etiological diagnosis when using the proposed threshold criteria of pao /fio ≤ mmhg. pao /fio ratio does not seem a good predictor of etiology in patients with vap. introduction: immunological dysfunction is common in critically ill patients but the optimal method to measure it and its clinical significance are unknown. levels of tumor necrosis factor alpha (tnf-α) after ex-vivo whole blood stimulation with lipopolysaccharide has been proposed as a possible method to quantitate immunological function. we hypothesized that patients with a lower post-stimulation tnf-α level would have increased rates of nosocomial infections (nis) and worse clinical outcomes. methods: a secondary analysis of a phase randomized, multicentre, double-blinded placebo controlled trial [ ] . there were no differences in allocation groups; all the patients were analyzed as one cohort. on enrolment, whole blood was incubated with lps ex-vivo and tnf-α level was measured. patients were grouped in tertiles according to delta and peak tnf-α level. the primary outcome was the development of nis; secondary outcomes included -day mortality. results: data was available for patients. baseline characteristics and outcomes are reported in tables and . patients in the highest tertile for post lps stimulation delta tnf-α compared to the lowest tertile were younger, had a lower acuity of illness and had lower baseline tnf-α. when grouped according to peak post-stimulation tnf-α levels, patients in the highest tertile had higher serum tnf-α at baseline. both comparisons showed no difference between nis and clinical outcomes between tertiles. in multi-variate analysis peak or delta tnf-α were not associated with the occurrence of nis. conclusions: admission ex-vivo stimulated tnf-a level is not associated with the occurrence of nis or clinical outcomes. further study is required to evaluate the ability of this assay to quantify immune function over the course of critical illness. results: sanitary and epidemiological examination revealed the connection between infection and intravenous infusion of dexamethasone performed concurrently with chemotherapy. in patients fever with chills and hypertension developed within hours after infusion of the infected drug; empirical intravenous antibiotic therapy started immediately after collecting blood culture. in patients fever appeared after - days outpatiently, so they received antibiotics per os. all these patients had permanent vascular access, and bsi was detected either the next chemotherapy course when fever reappeared ( pts) while using vascular access, or as a result of a specific examination ( pts). in all cases empirical antibiotic therapy started on the first day of fever, drug correction was performed in patients according to results of bacteriological research. septic shock developed in patient, pneumonia in patients. permanent vascular access was preserved only in case. all patients were cured and continued to receive antitumor treatment. conclusions: detection of more than case of b. cenocepacia bsi should be the reason for sanitary and epidemiological examination. a favorable outcome of bsi treatment is associated with the early start of antibiotic therapy and its correction after microbiological examination. emerging conclusions: implementation of asp in hospital allows to decrease incidence of eskape-bacteremia and candidemia, which may lead to improved clinical outcomes in icu's patients (fig ) . association of multi-drug resistant (mdr), extended-drug resistant (xdr) and pan-drug resistant (pdr) gram negative bacteria and mortality in an intensive care unit(icu) s chatterjee , s sinha , a bhakta , t bera , t chatterjee , s introduction: colistin-resistant klebsiella pneumoniae (cr-kp) is increasingly reported around the world. it is worrying to note emergence of resistance to last line of defence against mdr gram negative infections in regions endemic to carbapenem resistance. we report the first outbreak of cr-kp co-producing carbapenemases in an adult intensive care unit (icu) from south india. methods: retrospective analysis of all patients with carbapenem resistant klebsiella pneumoniae blood stream infection (bsi) was done between january and december . microbiological and clinical variables along with outcomes were analysed. results: seven patients had cr-kp with no prior exposure to colistin. all seven were modified hodge test (mht) negative making probability of blakpc unlikely. in resource limited setting, analysis beyond mht could only be performed for cr-kp samples. / samples belonging to cr-kp isolates produced the blandm- whilst / cr-kp isolates did not produce either blakpc or blandm carbapenemases prompting hypothesis of blaoxa- or blavim as the causative factor. compared to carbapenem resistance only group, cr-kp group had higher apache ii, icu length of stay and mechanical ventilation duration. day mortality was noted to be . % for carbapenem resistant and % for cr-kp groups. aggressive infection control measures were undertaken with successful containment of cr-kp strains along with reduction in overall bsi. conclusions: infection control measures form the backbone of patient care in centres showing endemicity for carbapenem resistant klebsiella to prevent colistin resistance and also to reduce occurrence of overall blood stream infections. rapid diagnosis of carbapenem resistance: experience of a tertiary care cancer center with multiplex pcr s mukherjee tata medical center, critical care medicine, kolkata, india critical care , (suppl ):p introduction: sepsis due to carbapenem resistant organisms has high mortality; inappropriate empirical antibiotic is one of the main causes of this poor outcome. on the contrary, "too much" broad spectrum empiric antibiotics will increase drug resistance, even in community, because of selection pressure. so, early diagnosis of resistance pattern (carbapenemase genes) is crucial. aim of this study is to compare rapid diagnostic test like polymerase chain reaction (pcr) with conventional culture sensitivity (c/s) to identify carbapenem resistance. methods: this is a prospective observational study done in tata medical center, kolkata, india. real time multiplex pcr technique has been developed "in house" in our microbiology lab and can identify ndm, ndm , kpc, oxa - , oxa - , oxa - & vim carbapenemase genes. blood cultures were sent as per clinical & laboratory diagnosis of sepsis in icu patients. culture positive samples had been used for conventional c/s by vitek system along with pcr study to identify carbapenemase genes. result of pcr technique was been compared with conventional c/s method. results: multiplex pcr results were available within - hours of positive blood culture compared to conventional c/s method that takes - days. among positive blood cultures, samples were positive for carbapenemase genes. most common gene identified was oxa - ( %), followed by ndm ( %). our pcr technique has very high sensitivity, specificity, positive & negative predictive value ( . %, . %, . % & . % respectively) while comparing with final c/s report by vitek system (table ) . there was only one false negative diagnosis for carbapenem resistance. conclusions: real time multiplex pcr for carbapenemase gene can be helpful for early diagnosis of carbapenem resistance and can help us to choose / modify antibiotics or to use 'targeted therapy'. it is more practical to "rule -in" infection rather than "rule -out" by this technique. carbapenemase producing enterobacteriaceae colonization in an icu: risk factors and clinical outcomes m miranda, jp baptista, j janeiro, p martins centro hospitalar e universitário de coimbra, intensive care unit, coimbra, portugal critical care , (suppl ):p introduction: carbapenemase-producing enterobacteriaceae (cpe) colonization has been increasingly reported in intensive care units (icus) since their first identification more than years ago. colonization with cpe seems to constitute a risk factor for mortality. the aim of our study was to identify associated risk factors and clinical outcomes among patients with fecal colonization by cpe admitted to a portuguese tertiary hospital icu. methods: a -year retrospective study was performed in patients with previous unknown cpe status (colonization or infection), admitted to our icu. rectal swabs were performed and analyzed using real-time polymerase chain reaction testing. clinical records were reviewed to obtain demographic and clinical data. results: of patients admitted, ( . %) harbored cpe, ( . %) were colonized at admission and ( . %) acquired cpe colonization during icu stay. the most frequent carbapenemase genes detected were kpc ( . %) and vim ( . %). cpe carriers had high rates of hospitalization (previous or ongoing), invasive procedures (mainly intraabdominal surgery), malignancy (hematopoietic or solid tumor), introduction: gram-negative pathogens-particularly pseudomonas aeruginosa and enterobacteriaceae-predominate in nosocomial pneumonia (np) and ciai both. these infections are becoming difficult to treat with available treatment options due to growing antimicrobial resistance in india. ceftazidimeavibactam has in-vitro activity against gram-negative organisms producing class a, class c and some class d beta-lactamases. we carried out a qualitative analysis to assess the safety and efficacy outcomes of the indian population cohorts involved in the re-prove and reclaim trials. methods: in line with the global reprove protocol, indian patients enrolled in the study with np, were randomly assigned ( : ) to mg ceftazidime and mg avibactam or mg meropenem. in the reclaim study, indian patients with a diagnosis of ciai were enrolled in the study and were randomly assigned ( : ) to receive either ceftazidime-avibactam ( mg of ceftazidime and mg of avibactam) followed by metronidazole ( mg); or meropenem ( mg). the primary efficacy outcome measure in the reprove and reclaim studies was clinical cure rate of caz-avi compared with that of meropenem at toc (test-of-cure) visit in pre-defined analysis sets. in both studies, non-inferiority was concluded if the lower limit of the twosided % ci for the treatment difference was greater than - · % in the primary analysis sets. as the indian subset study was not statistically powered to detect a difference in the subgroup, we descriptively analysed the efficacy results in the indian population and compared them with the overall results in the global trial. in addition, the study also analysed the safety of caz-avi in the indian patients by monitoring the number and severity of adverse events. introduction: early administration of effective intravenous antimicrobials is recommended for the management of the patients with sepsis. although meropenem (mepm) is one of the first-line drugs in patients with sepsis because of its broad spectrum, the optimal dose in the critical care settings especially during continuous renal replacement therapy (crrt) has not been established since therapeutic drug monitoring of mepm has not been popular. methods: eighteen critically ill patients who received crrt were enrolled in this study. one gram of mepm was administered over hour, every hours, and blood samples at , , , and hours after administration were collected on day , and . all samples were stored at - °c until analysis. the measurement of the blood concentration of mepm was performed using high performance liquid chromatography with ultraviolet detection (hplc-uv introduction: meningitis is one of the complications of severe traumatic brain injury, and it is often associated with encephalitis (incidence from . - . % to - %). the aim of the investigation was to study the dynamics of the concentration of meropenem in serum and cerebrospinal fluid (csf) with intravenous and intrathecal administration of meropenem. methods: in eight patients with bacterial meningoencephalitis blood serum and csf were studied prior to the administration of meropenem and - min, , . and hrs after it. antibiotic regimen: mg of vancomycin ( mg bid) and meropenem ( mg tid diluted in ml of saline iv + mg bid diluted in ml of saline bolus slowly intrathecally). meropenem infusion was carried out for minutes, mins after it ml of blood and ml of csf were sampled. prior to antibiotics administration blood and csf were taken for microbiological examination. to determine the concentration of antibiotics iquid chromatography/mass spectrometry was used. the samples were analyzed on an agilent infinity liquid chromatograph coupled to a sciex qtrap mass detector (sciex, us introduction: the prophylactic use of probiotics has emerged as a promising alternative to current strategies viewing to control nosocomial infections in a critically-ill setting. however, their beneficial role in vap prevention remains inconclusive. our aim was to delineate the efficacy of probiotics for both vap prophylaxis and restriction of icu-acquired infections in multi-trauma patients. methods: randomized, placebo-controlled study enrolling multitrauma patients, requiring mechanical ventilation for > days. participants were randomly assigned to receive either probiotic (n= ) or placebo (n= ) treatment. a four-probiotic formula was applied and each patient received two capsules per day from day to day post icu admission. the content of one capsule was given as an aqueous suspension by nasogastric tube, while the other one was spread to the oropharynx after being mixed up with water-based lubricant. the follow-up period was days, while icu stay and mortality were also assessed. ], while no difference in -day mortality rate was identified between groups ( . % probiotics vs . % placebo). conclusions: the prophylactic administration of probiotics exerted a positive effect on the incidence of vap or other icu-acquired infections and icu stay in a critically-ill subpopulation being notorious for its high susceptibility to infections, namely multi-trauma patients. use of a c-reactive protein-based protocol to guide the duration of antibiotic therapy in critically ill patients: a randomized controlled trial i borges introduction: the rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. in this study we aimed to evaluate the effectiveness of a c reactive protein (crp) based protocol in reducing antibiotic treatment time in critically ill patients. methods: an open randomized clinical trial was conducted in two adult intensive care units of a university hospital in brazil (clini-caltrials.gov: nct ). patients were randomly allocated to: i) intervention -duration of antibiotic therapy guided by crp levels, and ii) control -duration of therapy based on best in the intention to treat analysis, the median (q -q ) duration of antibiotic therapy for the index infection episode was . ( . - . ) days in the crp group and . ( . - . ) days in the control group (p= . ). in the cumulative suspension curve of antibiotics, a significant difference in the exposure time between the two groups was identified, with less exposure in the crp group (p= . ). in the pre-specified per protocol analysis, with patients allocated in each group, the median duration of antibiotics was . ( . - . ) days in the crp group and . ( . - . ) days in the control group (p= . ). mortality and relapse rates were similar between groups. conclusions: daily levels of crp may aid in reducing the time of antibiotic therapy in critically ill patients, even in a scenario of judicious use of these drugs. introduction: the macrophage activation syndrome (mas) or hemophagocytic lymphohistiocytosis(hlh) is a life threatening complication characterized by pancytopenia, liver failure, coagulopathy and neurologic symptoms and is thought to be caused by the activation and uncontrolled proliferation of t lymphocytes and well differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction [ , ] .the etiology is unknown, but is considered to have an infectious trigger.the aim of our study is to evaluate the impact of hlh in our beds infectious diseases icu, during months period ( - ). methods: a retrospective study based on electronic databases, including all patients admitted in our icu, that have matched at least out of criteria for hlh diagnosis ( ):fever; hepatosplenomegaly; > cytopenia (hb < g/dl, plt</dl, pmn -n< /mmc); hypertriglyceridemia> mg/dl, fibrinogen< mg/dl; hemophagocytosis-bone marrow, spleen, and/or lymphnodes; nk activity reduced/ absent; ferritin level> ui/l; cd > . we have evaluated the etiology established with cultures, serology, and molecular methods, treatment with corticosteroids, iv immunoglobuline, cyclosporine, etoposide and outcome ( ) . results: patients were admitted to icu, patients( . %) met the criteria for hlh. the average length of stay in icu was days; patients died ( %) without relation with the followed treatment. conclusions: hlh is not a rare condition in infectious diseases icu. the etiology is more frequent established compared with literature data. treatment (corticosteroids, immunoglobuline, cyclosporine, etoposide) is not associated with increased survival forecasting hemorrhagic shock using patterns of physiologic response to routine pre-operative blood draws introduction: irreversible hemorrhagic shock (ihs), a critical condition associated with significant blood loss and poor response to fluid resuscitation, can induce multiple organ failures and rapid death [ ] . determining the patients who are likely to develop ihs in surgeries could greatly help preoperative assessment of patient outcomes and allocation of clinical resources. methods: machine learning model of ihs is developed and validated via porcine induced bleed experiment. healthy sedated yorkshire pigs first had one ml rapid blood draw during a stable period, and then were bled at ml/min to mean arterial pressure (map) of mmhg. subjects had ihs defined as map< mmhg. arterial, central venous and airway pressures collected at hz during the blood draw [ fig ] were used to extract characteristic sequential patterns using graphs of temporal constraints (gtc) methodology [ ] , and a decision forest (df) model was trained on these patterns to determine subjects at high risk of impending ihs. results: in a leave-one-subject-out cross-validation, our method confidently identifies % ( % ci [ . %, . %]) of the subjects who are likely to experience ihs when subject to substantial bleeding, while only giving on average false alarm in , such predictions. this method outperforms logistic regression and random forest models trained on statistically featurized data [tab , fig ] . conclusions: our results suggest that by leveraging sequential patterns in hemodynamic waveform data observed in preoperative blood draws, it is possible to predict who are prone to develop ihs resulting from blood loss in the course of surgery. future work includes validating the proposed method on data collected from human subjects, and developing a clinically useful screening tool with our investigations. work partially funded by nih gm . introduction: the h s and oxytocin(oxy) systems are reported to interact with one another [ ] . h s plays a major role in the hypothalamic control of oxy release during hemorrhage [ ] . there is scarce information about oxy receptor(oxyr) expression in the brain in general and what is there is ambivalent. oxyr has been immunohistochemically(ihc) detected in the human hypothalamus but not in the hippocampus, in contrast to rodents [ ] , which underscores the need for additional characterization in relevant animal models. thus the aim of this study is to map the expression of the oxy and h s systems in the porcine brain in a clinically relevant model of hemorrhagic shock (hs). methods: anesthesized atherosclerotic pigs (n= ) underwent h of hs (map +/- mmhg) [ ] , followed by h resuscitation. ihc detection of oxy, oxyr, the h s producing enzymes cystathionine-γ -lyase (cse) and cystathionine-β -synthase(cbs) was performed on formalin fixed brain paraffin sections. results: oxy, oxyr, cse and cbs were localized in the porcine brain. proteins were differentially expressed in the hypothalamus (fig ) , parietal cortex and cerebellum (fig ) . cell types positively identified were: magnocellular neurons of the hypothalamus, cerebellar purkinje cells and granular neurons, and hippocampal pyramidal and granular neurons of the dentate fascia. arteries and microvasculature were also positive for oxyr and cse. conclusions: our results confirm the presence of oxy and oxyr in the hypothalamus similarly to the human brain. novel findings were: oxyr in the cerebellum and cse expression in the hypothalamus and cerebellum. the coexpression of oxyr and cse may link and help better understand neurochemical systems and physiological coping in hemorrhagic shock. funding: crc introduction: septic shock is one of the main causes of intensive care unit (icu) admission, leading to mortality up to % of patients. acute kidney injury (aki) frequently occurs and is associated to great morbidity and mortality. hemodynamic optimization may reduce the incidence of aki, but the use of vasopressors to increase mean arterial pressure (map) could have deleterious effect on renal perfusion. we aimed at investigating the effect of map and norepinephrine (ne) on the incidence of aki in septic shock patients methods: retrospective study based on prospectively collected data on digital medical records (digistat) at our icu. introduction: in patients with distributive shock, increasing mean arterial pressure (map) to a target of > mmhg can improve tissue perfusion. patients unable to achieve the target map of > mmhg despite adequate fluid resuscitation as well as catecholamines and vasopressin standard care (sc), may benefit from the noncatecholamine vasopressor angiotensin ii to increase map. this posthoc analysis examined whether patients from the athos- study with a baseline (bl) map < mmhg and treated with sc plus either angiotensin ii (ang ii) or placebo achieved a map of > mmhg for consecutive hours, without increasing the dose of sc therapy. methods: patients were assigned in a : ratio to receive ang ii or placebo, plus sc. randomization was stratified according to map (< or > mmhg) at screening. in patients with bl map < mmhg, we evaluated whether patients achieved a map of > mmhg for the first hours after initiation (map measurements taken at hours , , and ), without an increase in the dose of sc. results: among treated patients, had bl map < mmhg (ang ii, ; placebo, ). median bl map (iqr) was ( - ) and ( - ) mmhg for placebo and ang ii groups, respectively. patients with bl map < mmhg who were treated with ang ii were more likely to achieve map ≥ mmhg for consecutive hours after initiation without an increase in sc dose ( %, %ci - ), compared with placebo-treated patients ( %, %ci - , or= . , p< . ). conclusions: in this post-hoc analysis of patients with bl map < mmhg, patients receiving ang ii plus sc were significantly more likely to achieve a map > mmhg for the first consecutive hours after initiation than patients receiving sc only. this suggests that administering ang ii may help patients with catecholamine-resistant distributive shock to achieve the consensus standard target map. norepinephrine synergistically increases the efficacy of volume expansion on venous return in septic shock i adda, c lai, jl teboul, l guerin, f gavelli, c richard, x monnet hôpitaux universitaires paris-sud, hôpital de bicêtre, aphp, service de médecine intensive-réanimation, le kremlin-bicêtre, france critical care , (suppl ):p introduction: through reduction in venous capacitance, norepinephrine (ne) increases the mean systemic pressure (psm) and increases cardiac preload. this effect may be added to the ones of fluids when both are administered in septic shock. nevertheless, it could be imagined that ne potentiates in a synergetic way the efficacy of volume expansion on venous return by reducing venous capacitance, reducing the distribution volume of fluids and enhancing the induced increase in stressed blood volume. the purpose of this study was to test if the increase in psm induced by a preload challenge were enhanced by ne. methods: this prospective study had included septic shock adults. to reversibly reproduce a volume expansion and preload increase at different doses of ne, we mimicked fluid infusion through a passive leg raising (plr). in patients in which the decrease of ne was planned, we estimated psm (using respiratory occlusions) at baseline and during a plr test (plr high ). the dose of ne was then decreased and psm was estimated again before and during a second plr (plr low ). . the increase in cardiac index induced by plr low was significantly greater than that induced by plr high (p< . ). Δ psmhigh -Δ psmlow was moderately correlated with the diastolic arterial pressure at baseline-high (p= . , r= . ) and with the ne-induced change in mean arterial pressure (p= . , r= . ). conclusions: ne enhances the increase in psm induced by a plr, which mimics a fluid infusion. this suggests that it may potentiate the effects of fluid in a synergetic way in septic shock patients. this may decrease the amount of administered fluids and contribute to decrease the cumulative fluid balance. introduction: arginine vasopressin (avp) can be used in addition to norepinephrine (ne) for ne-resistant septic shock. however, a subgroup who will response to avp is unknown. the purpose of this study was to determine factors which could predict the response to avp in patients with ne-resistant hypotension. methods: this was a single-center, retrospective analysis of patients who administered avp for ne-resistant hypotension in our intensive care units (icus). eligible patients were adult patients who administered avp in addition to ne due to hypotension (mean arterial pressure (map) < ) in our icus between august and december . we divided all patients into two groups by response to avp; responders and non-responders. the responders were defined as an increase of map ≥ mmhg at h after avp initiation. we conducted univariate and multivariate logistic regression analysis to evaluate the effect of variables on avp response. results: a total of patients were included; responders ( %), non-responders ( %). there was no significant difference for map at the time of avp initiation ( vs mmhg; p = . ), initiation dose of avp ( . vs . u/min; p = . ), and dose of ne at the time of avp initiation ( . vs . μ g/kg/min; p = . ). map at h after avp initiation was significantly higher in responders than non-responders ( vs mmhg; p < . ). responders were older ( vs ; p = . ) and had lower heart rate (hr) ( vs. ; p = . ) and lactate ( . vs. . mmol/l; p = . ) at the time of avp initiation. the multivariate logistic analysis revealed that hr ≤ (or . , % ci . - . , p < . ), lactate ≤ (or . , % ci . - . , p < . ) and age ≥ (or . , % ci . - . , p = . ) were significantly associated with the response to avp. conclusions: hr, lactate levels and age before avp initiation can predict the response to avp in icu patients with ne-resistant hypotension. the maximum norepinephrine dosage of initial hours predicts early death in septic shock d kasugai , a hirakawa , n jinguji , k uenishi nagoya university gtaduate school of medicine, department of emergency and critical care, nagoya, aichi, japan; fujita health university, department of disaster and traumatology, fujita health university, toyoake, japan; fujita health university hospital, department of emergency and general internal medicine, fujita health university hospital, toyoake, japan critical care , (suppl ):p introduction: the mortality of septic shock refractory to norepinephrine remains high. to improve the management of this subgroup, the knowledge of early indicator is needed. we hypothesize that maximum norepinephrine dosage on the initial day of treatment is useful to predict early death in septic shock. methods: in this retrospective single-center observational study, septic shock patients admitted to the emergency intensive care unit (icu) of an academic medical center between april and march were included. cardiac arrest before icu admission and those with do-not-resuscitate orders before admission were excluded. the maximum dosage of norepinephrine initial hours of icu admission (md ) was used to assess -day mortality. results: one-hundred-fifty-two patients were included in this study. median sofa score was ( - ), and median md was . ( . - . ) mcg/kg/min. vasopressin and steroid were administered in ( %) and ( %) cases. nineteen patients ( %) died within a week. non-survivors had higher md , higher sofa score, and higher rate of vasopressin use. the higher md predicted -day mortality (area under curve . , threshold . mcg/kg/min, sensitivity %, specificity %). after adjustment of inverse probability of treatment weighing method using propensity scoring, md higher than . mcg/kg/min was independently associated with -day mortality (or: . , %ci: . - . , p < . ). conclusions: the maximum dosage of norepinephrine higher than . mcg/kg/min initial hours was significantly associated with day mortality in septic shock, and may be useful in the selection of higher severity subgroup. the impact of norepinephrine on right ventricular function and pulmonary haemodynamics in patients with septic shock -a strain echocardiography study k dalla sahlgrenska university hospital mölndal, göteborg, sweden critical care , (suppl ):p introduction: septic shock is characterized by myocardial depression and severe vasoplegia. right ventricle performance could be impaired in sepsis. the effects of norepinephrine on rv performance and afterload in septic shock are not immediately evident. the aim of the present study was to investigate the effects of norepinephrine on rv systolic function, rv afterload and pulmonary haemodynamics. methods: eleven, volume-resuscitated and mechanically ventilated patients with norepinephrine-dependent septic shock were included. infusion of norepinephrine was randomly and sequentially titrated to target mean arterial pressures (map) of , and mmhg. at each target map, strain-and conventional echocardiographic were performed. the pulmonary haemodynamic variables were measured by using a pulmonary artery thermodilution catheter. the rv afterload was assessed by calculating the effective pulmonary arterial elastance (epa) and pulmonary vascular resistance index (pvri). results: the norepinephrine-induced elevation of map increased central venous pressure ( %, p< . ), stroke volume index ( %, p< ), mean pulmonary artery pressure ( %, p< . ) and rv stroke work ( %, p= . ), while neither pulmonary vascular resistance index nor epa was affected. increasing doses of norepinephrine improved rv free wall strain from - % to - % ( %, p= . ), tricuspid annular plane systolic excursion ( %, p= . ) and tricuspid annular systolic velocity ( %, p= . ). there was a trend for an increase in cardiac index assessed by both thermodilution (p= . ) and echocardiography (p= . ). conclusions: the rv function was improved by increasing doses of norepinephrine, as assessed both by strain-and conventional echocardiography. this is explained by an increase of rv preload. pulmonary vascular resistance is not affected by increased doses of norepinephrine. peripheral perfusion versus lactate-targeted fluid resuscitation in septic shock: the andromeda shock physiology study. preliminary report g hernandez , r castro , l alegría , s bravo , d soto , e valenzuela , m vera , v oviedo , c santis , g ferri , m cid , b astudillo , p riquelme , r pairumani , g ospina- tascón table . conclusions: this preliminary results suggest that using crt as a target for fr in septic shock appears to be feasible, and not associated with impairment of tissue perfusion-related parameters as compared to lactate-targeted fr. grant fondecyt chile introduction: shock patients often become resistant to catecholamines which often require the addition of a non-catecholamine vasopressor. preclinical studies suggest that in the presence of aadrenoceptor antagonism, the renin-angiotensin aldosterone system exerts the major vasopressor influence. we sought to determine the effects of angii or lypressin (lyp [porcine vasopressin]) on blood pressure in a norepinephrine (ne)-resistant hypotension pig model. methods: phentolamine (phn), a reversible α-blocker that antagonizes the vasoconstriction by ne, was continuously infused to induce hypotension. after ne-resistant hypotension was established, lyp or angii was then co-infused with phn. mean arterial pressure (map) and heart rate were continuously recorded (fig. ) . results: as shown in fig. conclusions: in a background of α-adrenoceptor blockade, at clinically comparable doses, the vasopressor effect of ang ii was maintained while those of ne and lyp were attenuated. these data suggest that the blood pressure effect of vasopressin-like peptides may require a functioning α-adrenoceptor. patients with shock who are resistant to increasing doses of catecholamines may also have vasopressin resistance potentially making angiotensin ii a preferred vasopressor for these patients. introduction: resuscitative endovascular balloon occlusion of the aorta (reboa) has been increasingly used for the management of both traumatic and non-traumatic hemorrhagic shock. however, there is limited evidence for its use in gastrointestinal bleeding (gib), especially in the icu setting. we successfully treated a patient with massive gib using reboa in the icu. we will discuss the difficulty performing the procedure and its countermeasure. methods: a case report. results: an -year-old woman was transferred to our hospital with shock. coffee grounds material was found in a nasogastric aspirate after intubation and upper gastrointestinal endoscopy identified a pulsating large duodenum ulcer without active bleeding, for which an elective procedure was planned. she was admitted to our icu, responded to initial resuscitation, and thereafter extubated. her systolic blood pressure (sbp) suddenly dropped to mmhg with massive hematochezia at that night, and did not increase despite resuscitation with blood products, crystalloid and norepinephrine. to buy time until measures for stop bleeding, we planned to place reboa in the icu. following the placement of a sheath in the left femoral artery, we tried to place a fr intra-aortic balloon occlusion catheter, which unintentionally and repeatedly went into the right common iliac artery because her left femoral artery was tortuous. after compressing the right lower abdomen, we managed to introduce reboa in zone . it took approximately minutes to successfully place the catheter. the patient's sbp increased immediately after the balloon inflation and bleeding was endoscopically controlled. introduction: the natural components of the pomegranate fruit may provide additional benefits for endothelial function and microcirculation. we hypothesized that chronic supplementation with pomegranate extract might improve glycocalyx properties and microcirculation during anaerobic condition. methods: eighteen healthy and physically active male volunteers aged - years were recruited randomly to the pomegranate and control groups ( in each group). the pomegranate group was supplemented with pomegranate extract for two weeks. at the beginning and end of the experiment, the participants completed a high intensity sprint interval cycling-exercise (anaerobic exercise) protocol. the systemic hemodynamics, microcirculation flow and density parameters, glycocalyx markers, and lactate and glucose levels were evaluated before and after the two exercise bouts. results: no significant differences in the microcirculation or glycocalyx were found over the course of the study. the lactate levels were significantly higher in both groups after the first and repeated exercise bouts, and were significantly higher in the pomegranate group relative to the control group after the repeated bout: . ( . - . ) vs. . ( . - . ) mmol/l, p = . . conclusions: chronic supplementation with pomegranate extract has no impact on changes to the microcirculation and glycocalyx during anaerobic exercise, although an unexplained increase in blood lactate concentration was observed. introduction: extracorporeal membrane oxygenation in adults in accompanied by high mortality. our ability to predict who will benefit from ecmo based on currently available clinical and laboratory measures is limited. the advent of single cell sequencing approaches has created the opportunity to identify cell populations and pathophysiological pathways that are associated with mortality without bias from a priori cell type classifications. identification of such cell populations would provide both an important prognostic markers and key insight into immune response mechanisms and therefore a possibility for advanced drug matching that may impact clinical response to ecmo in these patients. methods: whole genome transcriptomic profiles were generated from a total of , peripheral blood monocytes obtained from patients at the time of cannulation for ecmo (fig ) . differential gene expression analysis was performed with the monocle package for the r statistical analysis framework. time-to-event data were analyzed in a survival analysis with a log-rank test for differences. results: genes encoding several members of the heat shock family of proteins were up-regulated in cells from non-survivors. notably, these genes were expressed by a small fraction of cells ( . % on average). nevertheless, the proportion of cells expressing these genes was a significant predictor of survival to days (p = . by log rank test), with a particularly pronounced effect in the first days after initiation of ecmo support (fig ) . conclusions: the proportion of cells expressing genes encoding members of the heat shock proteins is predictive of survival on ecmo. majority of pt ( %) had no known predisposing conditions, followed by immobility ( %) and cancer ( %). in ecg analysis tachycardia and v -v t wave inversion were the most common findings whereas hypoxemia± hypocapnia were the most prominent features in abg analysis. pt ( %) had bleeding complications (none intracranial), ( . %) during rtpa, ( . %) in the first h and only pt required transfusion. mortality rate was %: % directly due to pe (all during cpr) and % due to late complications (newly diagnosed cancer and infections). conclusions: in our experience, fibrinolytic therapy is safe and effective but in submassive pe should be applied after thorough assessment of risks and benefits on individual basis aiming to patient tailored precision medicine. [ ] trials evaluated the role of levosimendan in preventing low cardiac output syndrome in patients undergoing cardiac surgery. the studies were similar in their design and recruited patients with preoperatively low lvef undergoing either isolated cabg or valve surgery combined with cabg (table ). in both, a -hour levosimendan infusion was started at induction of anesthesia. neither study met the primary efficacy composite enpoints, but both showed a clear tendency for better outcome in patients undergoing a cabg compared to a valve procedure. we are currently evaluating the solidity of a co-analysis based on shared end-points. we are planning a shared analysed of the data related to the cabg settings and analyze the aggregated mortality data for both studies at and months by cochran-mantel-haenszel odds ratio. data from individual studies would be analysed as fixed effect and breslow-day test was used to evaluate homogeneity of the odds ratios results: in the placebo groups of the two studies, the mortality is similar; . % ( / ) in levo-cts and . % ( / ) in licorn, corroborating the working hypothesis that the two studies can be coanalysed. in a preliminary combined analysis (fig ) , -day mortality was . % ( / ) in the placebo group and . % ( / ) in the levosimendan group. odds ratio was significantly in favor of levosimendan ( . ; % confidence interval . - . ; p= . , fig. ) conclusions: the levo-cts and licorn trials can be co-analysed in their sub-setting of patients requiring isolated cabg surgery for mortality at and months. a preliminary analysis on mortality reinforce the hypothesis that, in isolated cabg surgery, levosimendan lowers post-operative mortality significantly both at and months, when started at the induction of anesthesia introduction: emergency medical system (ems) -based st elevation myocardial infarction (stemi) networks allows not only stemi diagnosis in the pre-hospital phase but also reduces treatment delays; treat your fatal complications and the immediate activation of the catheterization laboratory. the aim of study was to investigate the effect of out-of-hospital by mobile intensive care (micu) versus hospital beginning treatment in hospitalization length and survival of patients with stemi diagnosis introduction: contrast induced nephropathy (cin) is a complex acute renal failure syndrome, which can occur after primary percutaneous coronary intervention (pci) and is an important cause of morbidity and mortality in this subgroup of patients. the aim of our study was to establish the incidence and predictors of cin after primary pci. we performed a retrospective analysis of stemi patients treated with primary pci in the period from january until september of . cin was defined as an absolute increase in baseline serum creatinine of ≥ . mg/dl ( μmol/l) or > % relative rise within hours after primary pci. we analyzed demographic characteristics, risk factors, clinical status at hospital admission, laboratory parameters, left ventricle ejection fraction and data regarding pci procedure. results: the study included patients, with an average age of . ± . years, . % of the patients were males. an average of . ± . ml of contrast medium per patient was utilized. cin developed in ( . %) patients and overall intra-hospital mortality was . %. in multivariate analysis, the independent predictors of cin were age> years ( introduction: left main coronary artery (lmca) disease is a disease of the main coronary branch that gives more than % of blood supply to the left ventricle, it carries high mortality without surgical intervention; [ ] however the influence of lmca surgery on morbidity icu measures needs to be explored. we aim to determine whether lmca is definitive risk factor for prolonged icu stay as a primary outcome and whether lmca is definitive risk factor for early morbidity methods: retrospective descriptive study with purposive sampling analyzing patients underwent isolated coronary artery bypass surgeries (cabg). patients were divided into groups those with lmca disease as group ( patients) and those with coronary arty disease requiring surgery but without lmca disease as group ( patients) then we will correlate with icu outcome parameters including icu stay length, postoperative atrial fibrillation, acute kidney injury, re-exploration, perioperative myocardial infarction, post operative bleeding and early mortality. results: patients with lms had significantly higher diabetes prevalence ( . % vs %, p= . ). however, we did not find a statistical significant difference regarding icu stay, or other morbidity and mortality outcome measures conclusions: diabetes was more prevalent in patients with lms. the latter group showed similar outcome as those without lms in this study these findings may help in guiding decision making for future practice and stratifying the patients care. introduction: multimorbidity in patients admitted for acute myocardial infarction [ami] is associated with higher risk for in-hospital mortality and adverse clinical outcomes. we investigated to what extent an increasing number of comorbidities affects the age-stratified excess risk of death and other clinical outcomes among patients with myocardial infarction. methods: we analyzed nationwide administrative data of ` admissions for an acute myocardial infarction between and . we calculated multivariate regression models to study the association of four comorbidities (chronic kidney disease [ckd], diabetes mellitus, heart failure [hf], and atrial fibrillation) and excess risk of in-hospital mortality, length of hospital stay [los] , and -day readmission and stratified the analysis for different age categories. results: the incidence of admissions for ami increased continuously during the observed decade without an increase in in-hospital mortality, los, and -day readmission. among admitted patients with ami, there was a stepwise increase in risk for adverse outcomes for each comorbidity. compared to patients with no comorbidity, patients with comorbidities had -fold increased risk for mortality (adjusted odds ratio [or] . , % confidence interval [ci] . to . ) and a similar risk for readmission (or . , ci . to . ). the los was . days (ci . to . ) in patients with no comorbidity and increased by . days (ci . to . ) with each additional comorbidity. these associations were stronger in younger compared to older patients. ckd was the strongest predictor of in-hospital mortality and los, while hf was the strongest predictor of -day readmission. conclusions: this study of nationwide admitted patients with ami found a stepwise increase in the risk for adverse outcome with increasing number of comorbidities, particularly in the younger patient population. younger, multimorbid patients may thus have the largest benefits from multidisciplinary treatments. introduction: certified cardiac arrest centers, sophisticated post cardiac arrest care and prehospital ecls teams aim to increase survivor rates with a preferable neurological outcome after cardiac arrest. centers also provide emergency ecls and ecls pick ups for cardiogenic shock patients before arresting. few data answer the question of the long-term quality of life after ecls therapy. methods: in a retrospective single center register we included patients after emergency ecls (ecpr and cardiogenic shock) between / and / discharged alive and performed a follow-up after years on average at / . in our center criteria to initiate ecls therapy in cardiogenic shock or under cardiac arrest are an observed collaps, shockable rhythm, absence of frailty and severe comorbidities. all patients were requested to take part in a telephone interview. thus, we analyzed survival, cpc scores and sf scores. results: patients with hospital survival after ecls were screened. % (n= ) had survived until / ; patients were not accessible; had ceased. survivors (mean±sd; min-max; ± ; - years, women) answered sf questionaires ± ; - months after ecls ( % cardiogenic shock, % ecpr with shockable rhythm in %). the participantsĆ pc scores were in median . the results of the sf were physical functioning ± , physical role functioning ± , bodily pain ± , general health ± , vitality ± , social role functioning ± , emotional role functioning ± and mental health ± . survivors who did not take part at the sf had a cpc score of in median (n= , personally signed refusals, language barriers, vegetative states). conclusions: after emergency ecls therapy and hospital survival % of our patients survived the following years up to over years with a preferable neurological outcome and a general mentally and physically satisfactory quality of life. a vague outcome in % limits the results of our study. introduction: successful weaning from va-ecmo requires the restoration of a sufficient cardiac function to ensure an adequate tissue perfusion. skin blood flow (sbf) is among the first to deteriorate during circulatory shock and the last to be restored after resuscitation. sbf would be a good predictor of successful weaning from va-ecmo. methods: patients with va-ecmo, who required a first weaning attempt, were included. weaning procedure (wp) was performed by a reduction of va-ecmo blood flow to l/min for minutes. the weaning criterion was an aortic velocity-time integral (vti) > cm. successful weaning from va-ecmo was defined as hemodynamic stabilization and without the need to increase the vasopressor dose during the next hours. sbf, assessed by skin laser doppler (peri-flux , perimed, right index finger); perfusion unit: pu), together with global hemodynamic parameters were obtained before and after min of weaning. receiver operating characteristic curves (roc) were generated to assess the ability and reliability of baseline parameters to predict a successful weaning. results: we studied wps in patients with va-ecmo for pulmonary embolism (n = ), post cardiotomy (n = ), acute coronary syndrome (n = ), myocarditis (n = ). these were successful (sw) in and unsuccessful (nsw) in . at baseline, hemodynamic variables, lactate, ecmo blood flow were similar in both groups (table ). sbf was greater in sw than nsw patients (table ). during wp, ci rose from baseline and was similar in sw and nsw (p= . ) ( table ). vtis were higher in sw than nsw ( ( - ) vs ( - ), respectively, p= . ). sbf decreased in sw and remained low in nsw (table ) . from the roc curves analyses, baseline sbf had the highest area under the roc curve with a cut off ≥ pu (sensitivity %, specificity %) (figure ). conclusions: sbf is a good predictor of successful weaning from va-ecmo introduction: postoperative cognitive dysfunction (pocd) is defined as a temporarily decline in cognition associated with surgery. long-term pocd ( months after surgery) occurs in - % of cardiac patients and is associated with a higher morbidity and mortality. endo-cabg is a new minimally invasive endoscopic coronary artery bypass grafting (cabg) technique that requires retrograde arterial perfusion which may be associated with a higher incidence of neurological complications. the aim of this study is to assess the incidence of pocd after endo-cabg. methods: sixty consecutive patients undergoing an endo-cabg were enrolled. pocd was assessed following the recommendations of the " statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery". a comparative group of patients undergoing percutaneous coronary intervention (pci) and a control group of healthy volunteers were also enrolled. additional tests included the digit span test and digit symbol-coding test. patients were tested at baseline and at month follow-up. pocd is defined as a reliable change index (rci) ≤ - . (significance level %), or z-score ≤ - . in at least two different tests. results: after enrolling patients in each group, respectively in the endo-cabg-group, in the pci-group and healthy controls were analysed. patients suffering from a cva within three months after their procedure were automatically classified as having pocd (pci: n= ; endo-cabg: n= ). the total incidence of pocd was not different between groups (pci: n= ; endo-cabg: n= , p= . ). conclusions: our results suggest that the risk of pocd after endo-cabg is low and comparable with the risk of pocd after pci. introduction: rhabdomyolysis ( rml) post aortic surgery probably affects the renal outcome adversely [ , ] . there is no robust data regarding the same in literature. methods: retrospective single center data review; prior approval from institutional review board. patients were divided to two groups group -with rml ( ck above cut off levels u/litre) and group without rml. the determinants of rml and the impact of the same on outcome; predominantly renal function was evaluated. chi-square tests are performed for categorical variables whereas, student t tests (un-paired ) are performed with continuous variables. correlation is performed between creatine kinase and creatinine rise. p value . (two tailed) is considered for statistical significant level. results: out of patients, patients ( . %) developed rhabdomyolysis ( group rml) and did not( group non rml). demographic and intraoperative factors had no significant impact on the incidence of rml. there was a significantly higher incidence of renal complications including new postoperative dialysis in the rml group. other morbidity parameters were also higher in the rml group. conclusions: there is high prevalence of rml after aortic dissection surgery -identification of risk factor and early intervention might help to mitigate the severity of renal failure introduction: we investigate whether central venous pressure (cvp) pressure waveform signal can be informative in detection of slow bleeding in post-surgical patients. we apply a novel machine learning method to analyze cvp datasets to characterize bleeding in a porcine model of fixed rate blood loss. methods: thirty-eight pigs were anesthetized, instrumented with catheters, kept stable for minutes, and bled at a constant rate of ml/min to mean arterial pressure of mmhg. cvp waveforms were extracted from inspiration and expiration phases of respiration and statistically featurized. the proposed machine learning method, canonical least squares (cls) clustering, identifies correlation structures that differ between subsets of observations. we extend it to supervised classification. both clustering and classification methods yield human-interpretable models that reflect distinctive patterns of correlations within cvp waveforms. results: we conducted three experiments to discover structure in the physiological response to bleeding. first, we clustered respiration cycles with full knowledge of blood loss. the color-coded cluster assignments are shown in the figure . they are consistent with escalation of bleeding. second, we deployed clustering on only cvp features without blood loss. temporal structure was complemented with some subject-specific clusters (fig ) . third, we ran cls classification to decide whether an observation came from before or after the onset of bleeding (performance shown in the results: over the last decade, the number of patients with hlhs who underwent norwood has increased. interstage mortality has decreased, and is currently - %. significant morbidity was not seen at a rate higher than in the international literature. discharge planning, and community access to allied health professional services remained a concern. conclusions: the paediatric congenital cardiac surgical service in the united arab emirates is relatively new (compared to some services around the world). interstage mortality in hlhs is improving as a result of programme development, surgical progress and postoperative care. in the interstage period, there is currently no home monitoring programme in place. some patients were found to have had very extended hospital admissions. improved community support may reduce interstage mortality further, as well as improve the social situation of many of these patients. postoperative complications were observed in ( . %) patients. we lined out the prevalence of cardiac complications, such as heart failure and rhythm disturbances, observed in ( . %) and ( . %) patients respectively. hospital mortality rate was . % ( / ). the cause of mortality in all cases was acute heart failure, due to the initial severity of the disease, and in ( . %) cases an acute myocardial infarction was diagnosed. duration of postoperative period was . ± . days. conclusions: off-pump coronary artery bypass grafting can be safely performed with relatively low incidence of mortality and postoperative morbidity. prognostic value of mid-regional pro-adrenomedullin and midregional pro-atrial natriuretic peptide as predictors of multiple organ dysfunction development and icu length of stay after cardiac surgery with cardiopulmonary bypass in adults introduction: one of the most harmful complications after cardiac surgery with cardiopulmonary bypass is a syndrome of multiple organ dysfunction (mods). we consider that mid-regional proadrenomedullin (mr-proadm) and mid-regional pro-atrial natriuretic peptide (mr-proanp) plasma concentrations can be used as predictors of mods development and los in icu. methods: thirty six adult patients (mean age years, male) with cardiovascular diseases undervent cardiac surgery with cardiopulmonary bypass (heart valve(s) replacement - ( . %) patients, aorta and it`s branch surgery - ( . %) patients, valvular surgery and coronary artery grafting - ( . %) patients). nyha heart failure class ii was in ( . %) patients, iiiin ( %) patients, ivin ( . %) patients. in the dynamics levels of mr-proadm and mr-proanp were measured in the venous blood with the kryptor compact plus analyzer (thermo fisher scientific, germany) before day and on the st and th days after surgery. all patients were divided into subgroups according to the lengths of stay in the icu and the development of mod in the postoperative period. the data are shown as median and th and th percentiles. the data were compared by mann-whitney u-test, pvalue of < . was considered statistically significant. results: levels of mr-proanp did not significantly change at the study stages and did not have a significant difference between subgroups. the levels of mr-proadm increased in the first postoperative day and remained elevated for days. this increase was significantly higher in subgroups of increased los in icu and with mods. the data are shown in the table . conclusions: mr-proadm can be used as predictor of mods and los in the icu for adult patients underwent cardiac surgery with cardiopulmonary bypass. introduction: prolonged intensive care unit (icu) stay after cardiac surgery is associated with increased mortality and cost .the aim of this study was to investigate factors influencing prolonged icu stay. methods: consecutive patients who underwent cardiac surgery from june to october in our cardiothoracic department, were retrospectively investigated. group a consisted of pts with prolonged stay defined as more than days and group b the rest of the cohort. the following characteristics and perioperative factors were compared between the groups: smoking, diabetes, copd, redo(re-operation), ejection fraction (ef)< %, emergent procedure, cardiopulmonary bypass time (cpb)> min, low cardiac output syndrome (lcos), acute kidney injury(kdigo) and mortalitychi square test was used for the statistical analysis. introduction: hemorrhagic complications of extracorporeal membrane oxygenation (ecmo) pose a major morbidity and mortality. optimal anticoagulation strategies balancing risks of bleeding and thrombosis in children are poorly understood. we aimed to identify factors associated with non-surgical bleeding in the first ecmo hours. methods: we evaluated all pediatric (< yrs) post-cardiotomy patients requiring ecmo between dec -july stratifying them by presence/absence of surgical bleeding. non-surgical bleeding was defined as chest tube output > cc/kg/hr during the first -hours not requiring reoperation. patient characteristics and coagulation parameters at various time points after ecmo initiation were compared between groups, and receiver operator characteristic (roc) curves were constructed to identify models and thresholds with optimal predictive performance. figure . conclusions: deranged coagulation parameters, particularly kaolin rtime may predict non-operative bleeding in pediatric ecmo patients. these findings may guide therapeutic anticoagulation while avoiding hemorrhagic sequelae in at risk patients. introduction: elevated cardiac troponin (ctn) level in patients (pts) admitted in the intensive care unit (icu) is multifactorial and has been associated with a worse prognosis. the aim of the study was to review the frequency and the main cause of ctn elevation and to calculate a discriminating index. methods: we retrospectively assessed all pts admitted in our eightbed general icu during a -month period with at least one measurement of ctn during their icu stay. we recorded clinical characteristics, the level of ctn on admission, the maximum ctn during icu stay and the possible causes of elevation. variables are expressed as mean ± sd or as median and interquartile ratio (ir), according to the normality of their distribution. student´s Ô test or the mann whitney u tests were used to compare the group of elevated ctn with the group of normal ctn. the prognostic performance of elevated ctn was evaluated by the receiver operating characteristics (roc) curve. statistical analysis was performed using spss version . (spss, inc., chicago, illinois). results: in out of pts that ctn was measured at least once, abnormal levels (> . pg/ml) were found in ( %) of them, and the maximum ctn value was ( . ) pg/ml. the clinical characteristics of the pts are depicted in table . sepsis was the main cause of troponin elevation, which complicated by acute kidney injury (aki) in pts ( %). maximum ctn, aki and the difference of maximum -admission ctn (Äctn) differed significantly between pts who survived and pts who died (p= . and . , respectively). the area under the curve (auc) was . and the optimal prognostic cut-off value of Äctn was pg/ml with a sensitivity of . and a specificity of . conclusions: raised cardiac troponin values is a frequent finding in icu pts and sepsis is the driving cause. aki and the difference between maximum and admission ctn measurements differ significantly between pts who survive and pts who die. an elevation of ctn during icu hospitalization > pg/ml seems to be a threshold indicating poor prognosis regarding both mortality and aki. the prognostic role of nt-pro-bnp in septic patients with elevated troponin t level introduction: sepsis is frequently accompanied with release of cardiac troponin t (tnt) and nt-pro-bnp, but the clinical significance of this myocardial injury and cardiac dysfunction remains unclear [ ] . tnt is known to be an independent predictor of mortality, whereas the prognostic role of nt-pro-bnp is uncertain. methods: here, we report data of va-ecmo-patients, treated with dobutamine, levosimendan, suprarenin or no inotropic agens, in respect of -day survival. all data were collected retrospectively ( / to / ) at a single center, all patients with a survival below hours were excluded. while treatment of va-ecmo patients is strongly guided by standard operation procedures at our institution, no recommendation on positive inotropic therapy could be made. results: a total of va-ecmo patients were evaluated, of which patients were treated with levosimendan within hours after cannulation. day survival in the whole cohort was . %. a total of patients did not receive any positive inotropic therapy at hours after implantation (survival . %). survival was best in the levosimendan plus dobutamine group %, followed by dobutamine mono-therapy . % and levosimendan mono . %. survival with suprarenin mono was . %, suprarenin plus levosimendan . % and suprarenin plus dobutamine , %. pooling data, we found no evidence that levosimendan and/or dobutamine (survival . %, n= , p= . ) improves survival over no inotropic therapy (fig ) . therapy with any combination including suprarenin however resulted in poor survival ( . %, n= , p= . ). adjustment for lactate levels or ecpr did not change the results. conclusions: this retrospective analysis of va-ecmo patients shows no evidence that early inotropic therapy improves outcomes in va-ecmo patients. this conclusion is obviously biased by retrospective design. until randomized data are available, suprarenin however should be avoided. survey of non-resuscitation fluids in septic shock a linden-sonderso introduction: positive fluid balance is associated with poor outcome in septic shock. the objective of the present study was to characterize non-resuscitation fluids in early septic shock. methods: consecutive patients > years of age were screened for inclusion criteria during a -month period in icus in sweden and in canada. inclusion criteria were septic shock per sepsis- definition within hrs of icu admission. a maximum of patients per center were included. type, indication and volume of non-resuscitation fluids were recorded during the first days of admission. fluids other than colloids, blood products and crystalloids given at rate > ml/kg/h were considered to be non-resuscitation fluids. the study was registered on clini-caltrials.gov (nct ). data are presented as median (interquartile range). results: a total of patients were included between march st and june th (see table for demographics). patients received ( - ) milliliters (ml) of non-resuscitation fluids introduction: we aimed to ascertain the extent and make-up of fluid overload in critically ill patients and to identify whether delivery of more concentrated medications could reduce this. positive fluid balance is associated with increased mortality [ ] . a recent study has shown that the predominant component of fluid overload was from iv medications and maintenance fluid [ ] . methods: we reviewed sequential patients admitted to our icu with an apache ii score of greater than and a length of stay (los) greater than hours. the patients' electronic admission summary was interrogated to establish: length of stay (los) fluid balance at hours, total volume administered as iv medications, total volume administered as maintenance fluid and total fluid administered introduction: in children less than kilograms, maintenance fluids are routinely added to the resuscitation requirements calculated using parkland's or other formulae. the contribution of this component for fluid resuscitation in children can add a significant quantity to total estimated fluid requirements. for example, in a child who is kilograms with a % burn, the maintenance fluid requirement is mls per hours and the resuscitation component per parkland's will be x x %= mls. hence, the maintenance requirement can exceed the resuscitation requirement in this child if the burn surface area is less than a % burn. the contribution of maintenance fluids to the total fluid requirements in small children with thermal injuries is under-recognised and not frequently studied. methods: to understand the contribution of maintenance fluids to the total fluid requirements in children less than kilograms who need resuscitation for thermal injuries of different sizes, we numerically simulated . children who had similar weights but different burn sizes and . children with similar burn size but different weights. the results are as shown in fig introduction: accurate quantification of fluid in resuscitation of thermal injuries is important for benchmarking, comparing and improving outcomes. in adults, it is usually expressed as mls/kg/%tbsa. in children, maintenance fluids are added to the resuscitation requirements. this is kept constant and the resuscitation component is titrated to meet pre-defined end points-usually urine output. maintenance fluids are not uniformly stratified across the weight ranges. we propose that quantification of fluids in mls/ kg/%tbsa in children does not accurately capture fluid needs for resuscitation due to the maintenance component of the fluid requirement. methods: we conducted this retrospective study in children admitted to a single-center burns intensive care unit (bicu) between january and december . children ≤ kilograms with tbsa ≥ % admitted within hours of their injury were included. oe (observed to expected ratio) and fluid in mls/kg/% tbsa were calculated as shown in figure . results: there were children in the cohort with half requiring invasive mechanical ventilation in the bitu and nearly a quarter requiring inotropic support. the demographic details are as shown in table . the oe ratio at the end of hours in the cohort was . ( . - . ). the total fluid given was . ( . , ) mls/kg/ % tbsa. the titrated resuscitation component was . ( . , . ) mls/kg/tbsa. total fluid (which included the maintenance fluid) had a poor correlation with oe ratio r = . (fig ) . exclusion of the maintenance fluid had a better correlation with the oe ratio r = . conclusions: to capture differences in the titratable resuscitation component rather than differences in the maintenance requirements, fluid should be quantified in children by excluding the maintenance component when expressed as mls/kg/%tbsa. dynamic arterial elastance for predicting mean arterial pressure responsiveness after fluid challenges in acute respiratory distress syndrome patients p luetrakool , s morakul , v tangsujaritvijit introduction: dynamic arterial elastance (eadyn; pulse pressure variation/stroke volume variation; ppv/svv) is a dynamic parameter of arterial load that can be continuously monitored. previous study proposed that eadyn was able to predict mean arterial pressure (map) responsiveness after fluid challenge [ ] [ ] [ ] [ ] [ ] . the objective of this study was to assess whether the eadyn was able to predict map responsiveness in acute respiratory distress syndrome (ards) patients ventilated with low tidal volume. methods: we performed a prospective study of diagnostic test accuracy in adult ards patients with acute circulatory failure and fluid responsiveness. all patients are continuously monitored blood pressure via arterial line connected with flotrac® transducer and vigileo® monitor. once the attending physicians decided to load intravenous fluid, we recorded ppv/svv and also other hemodynamic parameters before and after fluid bolus. map responsiveness was defined as an increase in map ≥ % from baseline after fluid challenge. results: twenty-three events were included. nine events ( . %) were map-responsive. cardiac output, heart rate and stroke volume were similar in both map-responder and map-nonresponder group. baseline map, diastolic blood pressure (dbp) and pulse pressure (pp) were significantly different after fluid challenge in map-responder group. eadyn of preinfusion phase was failed to predict map conclusions: one of the arterial load parameters such as eadyn derived from non-calibrated pulse contour analysis method was unable to predict map responsiveness in ards patients with low tidal volume ventilation. the our aim is to test the hypothesis that in fr septic shock patients, fluid load will determine a significant increase in pmsf but not in cvp. we prospectively included all mechanically ventilated patients with diagnosis of septic shock with invasive hemodynamic monitoring (transpulmonary thermodilution volumeview-ev ed-wards©). we collected hemodynamic and metabolic data and pmsf with the inspiratory holds technique, before and after a fluid challenge (fc) of ml of ringer lactate in minutes). fr was defined as an increase in cardiac output (co)> %. results: measures were obtained in patients. in case we observed fr. we found a significant increase in pmsf after a fc (mean difference(md) . ± . mmhg, p=. ). cvp increased significantly (md . ± . mmhg, p=. ). pmsf increased significantly in non-fr (md ± mmhg, p=. ) but not in fr while cvp was higher after fc only in fr (md . ± . mmhg, p=. ). venous return gradient (pmsf-cvp) globally increased after fc (md ± mmhg, p=. ), but only in non-fr such increase was significant (md ± mmhg, p=. ). no correlation was found between the variation co and venous return gradient. we did not find any improvement in metabolic parameters after the fluid challenge. conclusions: pmsf and combined cvp variations do not correlate with fr in our cohort of septic shock patients. inspiratory holds may not be adequate to infer pmsf in such context. further studies are warranted to investigate the effect of fc on pmsf in this field. evaluation of pre-load dependence over time in patients with septic shock i douglas , p alapat , k corl , m exline , l forni , a holder , d kaufman , a khan , m levy , g martin , j sahatjian , w self , e seeley , j weingarten , m williams , c winterbottom , d hansell is an effective method to predict fluid responsiveness (fr) or cardiac response to preload expansion. we have previously shown that fluid responsiveness is a dynamic state, changing frequently over a hour monitoring period. methods: fresh is a currently enrolling prospective randomized controlled study, evaluating the incidence of fr and patient centered outcomes in critically ill patients with sepsis or septic shock (nct ). patients randomized to plr guided resuscitation were evaluated every - hours over the first hours of care and classified as fr if the sv increased > % when measured with non-invasive bioreactance (starling sv, cheetah medical). the time of first fr was noted. results: a total of plr assessments were performed in patients over a hour monitoring period. % were female, and the average age was years. plrs were evaluated over time, with time representing initial fluid resuscitation ( figure ). when individual subjects were evaluated over time, % of subjects who became fr only after hours showed evidence of lv/rv dysfunction ( figure ). conclusions: fluid responsiveness or preload dependence frequently changes for septic shock patients over the first hours of care. evidence suggests it is beneficial to periodically perform an assessment of preload responsiveness to guide fluid administration, as preload dependence is a dynamic and changing state. preload dependence provides additional information beyond fluid responsiveness. those patients who remain primarily fluid non-responsive (preload independent) are more likely to demonstrate echo confirmed lv/rv dysfunction, as the delay in return to cardiac function may be related to underlying cardiac deficits. further evaluation may be indicated in preload independent patients. introduction: hydroxyethyl starch (hes), a synthetic colloid, has been used as a volume expander, and is associated with renal impairment in patients with sepsis. however, a small dose of hes ( %, / . ) has sometimes been used in acute ischemic stroke. therefore, we investigated whether a small dose of hes was linked with renal deterioration in patients with acute ischemic stroke. methods: a consecutive patients with acute ischemic stroke within days from onset were included between january and may (fig ) . we collected admission serum creatinine (scr), estimated glomerular filtration rate (egfr), and renal function was assessed using kdigo definition of acute kidney injury on hospital days to as to patient's hospitalization period. is crucial for venous return and volaemic status, and as such it is a useful parameter in physiology and clinical settings alike. we tested whether: near infra-red spectroscopy (nirs) could be effective at measuring msfp both in healthy individuals and in conditions with a rise in interstitial pressures; after an occlusion pressure is relieved, the decrease in venular blood volume could allow calculation of τ (time constant) and thus venous resistances (rv). in order to verify these hypotheses we used a forearm nirs probe on healthy individuals at rest and during different degrees of maximal voluntary contraction (mvc). methods: healthy subjects volunteered in the study that took place at sant'andrea hospital in rome (italy). all subjects had venular pressures and volumes assessed via a nirs probe positioned on the forearm using a pressure-cuff in steps of mmhg from to mmhg, at rest and at % and % mvc. for each patient msfp, unstressed volume (vu) and stressed volume (vs) were measured. a temporary mmhg occlusion was obtained and volume time course was calculated upon release, to derive τ . results: p-v relationship was found to have a -slopes shape reflecting venular network changes. we measured vu, vs, and obtained msfp values of . ± . mmhg, p< . ; during exercise no changes in vu and vs were noted but msfp values rose; value was found to be . ± . sec at rest and . ± . sec after exercise, reflecting a reduction in rv. conclusions: nirs measurements on healthy subject may have implications in the clinical assessment of critical care patients where changes in interstitial pressure are possible. introduction: in the pathogenesis of multiple organ dysfunction syndrome (mods) important role plays the development of hepatic dysfunction. a known method for assessing hepatic blood flow is reohepatography (rhg). however, it requires the analysis of a large number of parameters of the rheogram curve. the aim of this study was to develop a method for assessing arterial hepatic blood flow based on the rhg in patients with mods after abdominal surgery. methods: patients in the department of anesthesiology and intensive care unit were included in a prospective study ( men and women, age . ± . years, weight . ± . kg.). all patients were divided into two groups: group -patients after orthopedic and trauma surgery (n = ), group -patients after abdominal surgery with mods (n = ). patients in the groups did not have statistical differences by sex, age, body weight, height. rhg was carried out using the "reo-spectr" (russian federation). we have compared the rhg indicators between the groups ( table ) . we have developed a method for assessing hepatic arterial blood flow, which consists in determining the area under the arterial part of rhg curve using the simpson's rule. its normal values range from . mΩ *s to . mΩ *s. the method is non-invasive, can be applied at the patient´s bed. its advantage is simplicity, it can be used for rapid diagnosis and monitoring the effectiveness of treatment. area under the rhg curve in the group were . ± . mΩ *s and . ± . mΩ *s in the group (p < . ). conclusions: patients after abdominal surgery with mods have impaired hepatic blood flow, which may be associated with liver pathology caused by main surgical disease (obstructive jaundice) and hemodynamic disorders caused by acute cardiovascular failure. the method we developed allows us to determine disorders of hepatic arterial blood flow in the early stages before signs of liver dysfunction appear. comparison of pulse oximetry hemoglobin with laboratory measurement of arterial and central- results: patients: % male, median years ( - ); p:f ratio ( - ); peep ( - ); apache iii . ( ); median ventilation time days ( - ). fair agreement was seen in subjective assessment vs objective measures with binary assessment of rv size and function. ordinal data analysis showed poor agreement with rvfws ( figure ) and rv dimensions. if onestep disagreement was allowed the agreement was good ( table , ). significant overestimation of severity of abnormalities was seen comparing subjective assessment with rv eda and tapse, s' and fac. there was no difference in agreement values when accounting for clinician echo experience, perceived expertise (at level of cardiologist) or type of qualifications. conclusions: relatively low levels of agreement were seen with subjective assessment vs objective measures of rv size and function assessed by echo. it seems prudent to avoid subjective rv assessment in isolation and a combination of objective and subjective measures should be used. introduction: even short periods of hypotension are associated with increased morbidity and mortality. using high-density numerical physiologic data, we developed a machine learning (ml) model to predict hypotension episodes, and further characterized risk trajectories leading to hypotension. methods: a subset of subjects with / hz physiological data was extracted from mimic , a richly annotated multigranular database. hypotension was defined as > measurements of systolic blood pressure ≤ mmhg and mean arterial pressure ≤ mmhg, within a -minute window. derived features using raw measurements of heart rate, respiratory rate, oxygen saturation, and blood pressure were computed. random forest (rf), k-nearest neighbors (knn), and logistic regression models were trained with -fold cross validation to predict instantaneous risk of hypotension using features extracted from the data leading to the first episode of hypotension (cases) or icu discharge in subjects never experiencing hypotension (controls). for a given subject, risk trajectory was computed from the collation of instantaneous risks. results: from a source population of subjects, subjects met our definition of hypotension, and subjects without hypotension comprised the control group. features were generated from the four vital signs. the area under the curve (auc) for random forest classifier was . , out-performing logistic regression (auc . ) or k-nearest neighbors (auc . ) (fig ) . risk trajectories analysis showed average controls risk scores < . (< % risk of future hypotension), while the hypotension group had a rising risk score ( . to . ) in the hours leading to the first hypotension episode, and significantly higher scores leading into subsequent episodes (fig ) . conclusions: hypotension episodes can be predicted from vital sign time series using supervised ml. subjects developed hypotension have an increased risk compared to controls at least hours prior to the episode. introduction: in critically ill patients or in patients undergoing major surgery, monitoring of co is recommended [ ] [ ] [ ] . less-invasive advanced hemodynamic monitoring with pwa is increasingly used in perioperative and critical care medicine. in this study, we evaluate the measurement performance of an uncalibrated pulse wave analysis (pwa) device (mostcareup, vygon, ecouen, france) compared with cardiac output (co) assessment by pulmonary artery thermodilution (patd) in patients after cardiac surgery. methods: in patients after cardiac surgery, we performed seven sets of patd measurements to assess patd-co. simultaneously, we recorded the pwa-co and compared it to the corresponding patd-co. to describe the agreement between pwa-co and patd-co we used bland-altman analysis showing the mean of the differences and %-limits of agreement and calculated the percentage error. results: we included patients in the analysis. the bias between pwa-co and patd-co was . l*min- . upper and lower % limits of agreement were + . l*min- and - . l*min- . the percentage error was . %. conclusions: pwa-co estimated with using the mostcareup device shows good agreement with pulmonary artery thermodilutionderived co in patients after cardiac surgery. introduction: non-invasive continuous blood pressure monitoring devices have been investigated, however, these devices did not have sufficient accuracy and precision. we developed a continuous monitor using the photoplethysmographic technique and tested the accuracy and precision of this system to ensure it was comparable to conventional continuous monitoring methods used for critically ill patients. methods: the study device was developed to measure blood pressure, pulse rate, respiratory rate, and oxygen saturation, continuously with a single sensor using the photoplethysmographic technique. patients who were monitored with arterial pressure lines in the icu were enrolled. the physiological parameters were measured continuously for minutes at -minute intervals using the study device and the conventional methods. the primary outcome variable was blood pressure. results: pearson fs correlation coefficient between the conventional method and photoplethysmography device were . for systolic blood pressure, . for diastolic blood pressure, . for mean blood pressure, . for pulse rate, . for respiratory rate, and . for oxygen saturation. percent errors for systolic, diastolic and mean blood pressures were . % and . % and . %, respectively. percent errors for pulse rate, respiratory rate and oxygen saturation were . %, . % and . %, respectively. conclusions: the non-invasive, continuous, multi-parameter monitoring device presented high level of agreement with the invasive arterial blood pressure monitoring, along with sufficient accuracy and precision in the measurements of pulse rate, respiratory rate, and oxygen saturation. conclusions: stroke volume measurement using bioreactance technique had strong correlation with odm while pwtt had moderate correlation. both devices had small bias with wide limits of agreement and percentage error compared with odm. therefore, these devices are not interchangeable with odm. however, using trends in stroke volume to guide treatment might still be acceptable. introduction: hemorrhage is the most common cause of trauma deaths and the most frequent complication of major surgery. it is difficult to identify until profound blood loss has already occurred. we aim at detecting hemorrhage early and reliably using waveform vital sign data routinely collected before, during, and after surgery. methods: we use waveform vital sign data collected at hz during a controlled transition from a stable (non-bleeding) to a fixed bleeding state of pigs. these vital signs include airway, arterial, central venous and pulmonary arterial pressures, venous oxygen saturation (svo ), pulse oximetry pleth and ecg heartrate, continuous co, and stroke volume variation (lidco). we used gated recurrent units (gru), long short-term memory (lstm) and dilated, causal, one-dimensional convolutional neural (table ) . however, outside of the very low fpr range (cf. rocs in fig. and ), our models appear inferior to a referenced random forest (rf) classifier. conclusions: our work demonstrates the applicability of deep learning models to diagnose hemorrhage based on raw, waveform vital signs. future work will address why the rf classifier can address the greater homogeneity of subjects when they bleed compared to an apparently wide dispersion of their statuses when being stable. this work is partially supported by nih gm . can myocardial perfusion imaging with echo contrast help recognise type acute myocardial infarction in the critically ill? introduction: many instances of significant bleeding may not occur in highly monitored environment, contribution in the delay in recognition and intervention. we therefore proposed a noninvasive monitoring for early bleeding detection using photoplethysmography (ppg). methods: fifty-two yorkshire pigs were anesthetized, stabilized and bled to hemorrhagic shock, and their invasive arterial blood pressure (abp), and ppg data were collected [ ] . time series of vital signs were divided into data frames of minute updated every seconds and beat to beat features were computed. the final feature matrix contained abp features and ppg features. a supervised machine-learning framework using least absolute shrinkage and selection operator regularized logistic regression model was constructed to score the probabilities for hemorrhage of each data frame. data in stabilization was set as negative and data in bleeding was set as positive. model performance was evaluated by receiver operating characteristic (roc) area under the curve (auc) with leave-one-out cross validation, and its precision was assessed with activity monitoring operative characteristic (amoc). results: two different models were proposed using abp and ppg features separately. figure showed the ppg model could classify the hemorrhage with auc = . , where the auc of abp model was . . figure showed the ppg model could detect the hemorrhage on average . minutes (equals to ml blood loss) if the false alarm rate of / was tolerated, whereas the average detection time of abp model were . minutes at same threshold of false alarm rate. conclusions: we proposed a novel non-invasive bleeding detection approach using ppg signals only. this method potentially can improve the identification of hemorrhage with in patients and environments where invasive monitoring is unavailable. table , catheter and procedure characteristics are shown in table . the median angle of bed position was °. no patients were positioned in neutral or tp. all procedures were successful with a mean of . punctures per patient, and a maximum of . the median procedure time was . minutes. no major complications occurred in any of our patients. conclusions: central venous catheterisation in moderate upright position is feasible and can be done safely when using realtime ultrasound by well-trained physicians. we recommend performing clinical assessment and pre-procedural ultrasound to choose the optimal puncture site and position in order to attain an optimal ultrasound visualisation of the vessel and patient comfort. methods: a retrospective analysis of patients presenting to tertiary-care emergency department who required cvc for vasopressor administration was carried out. all central venous cannulation into the right brachiocephalic vein was performed with ultrasound guidance using the high frequency linear probe. right brachiocephalic vein was visualised in its long axis. the needle was positioned just beside the centre of ultrasound probe degrees below the coronal plane and degrees angle to the ultrasound probe and advanced just behind the clavicle. results: the mean puncture time taken to perform this procedure, calculated from the needle piercing the skin until to the aspiration of blood from the brachiocephalic vein through the needle, was ± . s. no procedure-related complications were detected. conclusions: the oblique needle trajectory of right brachiocephalic vein cvc in adult is feasible and able to visualised well the anatomical structure, hence avoid complications. introduction: central venous cannulation, a routine procedure on intensive care units, is associated with a low complication rate. as a consequence, the routine use of chest x-ray (cxr) or ultrasound (us) to assess these complications is under discussion. our aim was to identify risk factors for central venous catheter (cvc) placement associated complications that can help decide whether or not follow-up using cxr and/or us is indicated. methods: multicenter prospective, observational study. consecutive critically ill adult patients who underwent cvc placement. either the internal jugular vein or subclavian vein was cannulated. complication rates were determined. predicting factors were obtained through a questionnaire filled in by physicians after placing a cvc. if the questionnaire was incomplete or data was missing, analyses were performed using the available data. patient characteristics were duplicated if a patient recieved more than one cvc. outcomes were iatrogenic pneumothorax and malposition. pneumothorax was detected using us, whereas cxr was used to determine cvc malposition. table . usguidance, insertion site, and setting were predictive for complications. the overall cvc placement associated complication rate is low and multiple risk factors associated with the occurrence complications were identified. a complication rate this low, strongly suggests that routine post-procedural diagnostics is superfluous. therefore, we suggest, provided that uneventful execution of the procedure is assured, post-procedural diagnostics are only necessary in selected cases with (multiple) risk factors. introduction: the use of ultrasound for subclavian vein cannulation (scv) has developed poorly due to the difficulty of visualizing this vein via the classical infraclavicular approach. we explored the feasibility of ultrasound-guided subclavian vein catheterization via a supraclavicular approach methods: prospective study conducted over six-month period in intensive care unit. after approval of the ethics committee, we included patients over years of age and requiring central venous access. exclusion criteria were: hemostasis disorders, puncture area infections and cervico-thoracic vascular malformations the procedure consisted of catheterization of the vsc with a supraclavicular approach under ultrasound guidance using an ultrasound in plane approach (fig and ). data collection included clinical and ultrasound data: scv depth, diameter and length, catheterization time, number of needle redirection, cannulation success and complications. results: thirty four patients were included. age: ± (mean ± sd), % of whom were male. the success rate of scv catheterization was % (one failure). the depth of the scv was ± . mm and its diameter was ± . mm. the puncturable length of the scv was ± mm and the puncture angle was ± °. the time required to obtain an adequate ultrasound image was ± seconds. the interval between the beginning of the puncture and the insertion of the guidewire into the vein was ± sec. the total catheterization time was ± seconds. the number of needle redirection . +/- . redirects. the quality of the ultrasound image was excellent or good in . % of cases. an arterial puncture was observed in two patients conclusions: this preliminary study demonstrated the feasibility of the subclavian vein cannulation via the supraclavicular approach. more study are required to confirm its safety and to compare this approach to the infraclavicular acces using ultrasound. introduction: lung ultrasound b-lines, a comet-like reverberation artefacts arising from water-thickened interlobular septa, indicate extravascular lung water which is a key variable in heart failure management and prognosis. aim of this study is to measure the correlation between lung ultrasound b-lines and nyha functional classification. methods: this is a months prospective study on congestive heart failure patients conducted in urban emergency departments in malaysia. following enrolment, patients had their functional capacity categorised based on nyha classification, followed by point of care ultrasound (pocus) lung scan using a mhz linear probe. the scanning was performed by trained emergency physicians. the longitudinal scan done at the recommended zones of both left and right lungs and the total number of b-lines identified were summed up as the comet score. comet score of , , and were categorised based on amount of blines of less than , - , - and more than b-lines respectively. results: hundred and twenty-two patients were analysed ( males( . %) and females( . %)) ranging from to years old. comet score of , and were found to be statistically significant with presence of paroxysmal nocturnal dyspnoea, elevated jugular venous pressure, lung crackles, bilateral pitting oedema and chest radiographic findings. a moderate correlation between nyha classes with comet score , and (rs= . (p< . )) was documented. conclusions: our study demonstrated a moderate correlation between nyha classes and lung ultrasound b-lines. lung ultrasound may be a potential tool to objectively determine the functional capacity in patients with congestive heart failure and monitor its changes in response to treatment and disease progression. the introduction: point of care ultrasound (pocus) is a tool of increasing utility in the management of the critically ill patient. guidelines exist for training and accreditation in pocus [ , ] however the widespread use of pocus has been hampered by a lack of mentors. online communication with end-to-end security, such as whatsapp ™ are increasingly used in medicine as a communication aid [ ] . some individuals are using such communications to share pocus images for review-the overall sentiment around these tools is unknown. methods: an online survey of pocus users was conducted via twitter ™. the question was "in situations where an expert opinion on an ultrasound is not immediately available, is it acceptable to get an expert review via an online medium such as whatsapp, and would you be happy to be that expert?" results: votes were received. voters were a mix of pocus users from the usa, europe, and australia. % said the medium was acceptable, and that they would be happy to provide expertise. % voted "no", with % voting "other" (fig ) . conclusions: in this international survey of pocus users, % were happy to provide and receive mentorship using remote software such as whatsapp. distance mentorship for pocus training should be explored. [ ] . a description of the development and refinement of insight -a feasibility and clinical effectiveness randomized controlled trial. methods: a modified delphi exercise was used to select the most beneficial ultrasound windows and imaging questions to ask for each window in scheduled inter-professional ultrasound. nurses, doctors and physiotherapists from critical care were given the same information regarding potential utility of each window. the windows and associated questions were individually ranked; each window and question tested against three further criteria; and filtered by ease of training to level standard; clinical usefulness; time of practical delivery and applicability across an inter-professional group. results: the modified delphi exercises and prioritization exercise ranked ease of adoption by training; feasibility within the time frame and clinical usefulness to develop a core insight scan of domains, each with set binary questions (tables and ) conclusions: we have developed a research intervention that will allow us to test the effectiveness of inter-professional scheduled whole body assessment of critically ill patients by ultrasound. we now plan to conduct a clinical effectiveness trial with an internal pilot to confirm feasibility. to search for optimal pressing time, the plots from the color sensor during nail bed compression were analyzed. we found two phases in the color sensor plots. in the initial part of compression, the plots changes rapidly (rapid phase) and then the slope of plots reduces (slow phase). the pressure release during the rapid phase could destabilize the measurement. the longest period of the rapid phase was . s among all the study subjects. thus, a pressing time of s seems to be needed to obtain stable crt measurements. conclusions: on our study for the investigation of standard pressing time and strength for crt measurements, pressing the nail bed with - n and s appears to be optimal. detection of pancreas ischemia with microdialysis and co sensors in a porcine model introduction: pancreas transplantation is associated with a high rate of early graft thrombosis. current postoperative monitoring lack tools for early detection of ischemia, which could precipitate a graft-saving intervention. we are currently exploring the possibility of ischemia detection with microdialysis and co -sensors in the organ tissue or on the surface in a porcine model. methods: in anesthetized pigs, co -sensors and microdialysis catheters are inserted into the parenchyma or attached to the surface of the pancreas. pco is measured continuously and lactate is sampled with microdialysis every min. ischemia is induced by sequential arterial and venous occlusions for minutes, with minutes of reperfusion in between. results: pco increased and decreased in response to ischemia and reperfusion within minutes. lactate increased and decreased with the same pattern, but with a considerable delay as compared to pco . an example is depicted in figure . the values are presented in introduction: reliable automated handheld vital microscopy (hvm) image sequence analysis is a prerequisite for use of sublingual microcirculation measurements at the point-of care according to the current consensus statement. we aim to validate a recently developed advanced computer vision algorithm [ ] versus manual analysis in a wide spectrum of populations and contexts. methods: our collaborators were invited to contribute raw data of published or ongoing institutional review board approved work. inclusion criteria were use of the cytocam hvm device, manual analysis with the ava software, and image quality as independently assessed by massey score of < in > % of recordings in a random subset of each study. subjects from studies were included, covering clinical and experimental populations, major shock forms and interventions to recruit the microcirculation (table ) . results: , , red blood cells were tracked by the algorithm across , frames in measurements in real time. a good to excellent correlation was found between algorithm-determined and manual capillary density (p< . , r . - . , figure ). capillary perfusion was classified using space-time diagram derived red blood cell velocity (rbcv), yielding good correlation with manual analysis for functional capillary density und proportion of perfused vessels. microcirculatory alterations during disease and interventions were equally detected by the algorithm and manual analysis. change in flow short of severe abnormality was reflected in absolute rbcv but not microcirculatory flow index. conclusions: we demonstrate the validity of automated software for hvm image sequence analysis across broad populations, disease conditions and interventions. thus, microcirculatory assessment at the bedside may finally complement point-of-care evaluation of disease severity and treatment response in critically ill patients and during surgery. introduction: in , naumann et al introduced the poem score as a real-time, point-of-care score to assess sublingual microcirculation [ ] . our study aimed to determine the reproducibility of the poem score. methods: two expert operators used a sidestream darkfield (sdf) videomicroscope (cytocam, braedius, netherlands) to separately acquire four high-quality video clips and assign a poem score to each image in adult mechanically ventilated patients. each operator was blinded to the other's images and analysis. video clip scores and acquisition times were recorded. results: of the patients enrolled in this study, % (n= ) required vasopressors. we categorized poem scores - as "normal" and poem scores - as "impaired." (fig ) . with only one instance of interrater disagreement (i.e., a single image scored as versus ), cohen's kappa ( . ) confirmed a strong correlation between interpreters. the mean time to complete a study session was minutes. conclusions: the present inability to quickly characterize the quality of sublingual microcirculation as either normal or impaired at the point of care limits real-world clinical application of this resuscitative endpoint. the rapidly obtained poem score appears to be reproducible between bedside interpreters. future studies should assess the effect of poem score-guided resuscitation. . sublingual microcirculatory images were obtained using a cytocam-idf device (braedius medical, huizen, the netherlands) and analyzed using standardized published recommendations. results: the median age of participants was years. we found no significant difference in proportions of hemodynamic responders before and after marathon ( % vs %, p= . ). also we did not find differences between plr induced changes of total vessel density (tvd) and proportion of perfused vessels (ppv) of small vessels before and after marathon. correlations between changes of sroke volume and changes of tvd or ppv of small vessels during plr were not significant. conclusions: marathon running did not change microcirculatory responsiveness. introduction: clinical measurement of mitochondrial oxygen tension (mitopo ) has become available with the comet system [ ] . a question with any novel technique is whether it is feasible to use in clinical practice and provides additional information. in elective cardiac surgery patients we measured cutaneous mitopo and tissue oxygenation (sto ). methods: institutional research board approved observational study in patients undergoing cardiopulmonary bypass (cpb). mitopo measurements were performed on the left upper arm (comet, photonics healthcare b.v.) by oxygen-dependent delayed fluorescence of aminolevulinic acid (ala)-induced protoporphyrin ix [ ] . priming of the skin was done with ala (alacare, photonamic gmbh) applied the evening before surgery. sto measurements (invos, medtronic) were done in close proximity to the comet sensor. results: at the time of writing of patients were enrolled and mitopo measurements were feasible in this clinical setting. mitopo appeared sensitive with a high dynamic range. for example, highdose vasopressor therapy decreased mitopo and blood transfusion increased a low mitopo but not a high mitopo . in the example in figure , mitopo is clearly dependent on cpb flow and the restored cardiac circulation is able to maintain good cutaneous oxygenation after cpb even before returning of cellsaver blood. sto had the tendency to provide relatively stable values within a small bandwidth and little response to even major hemodynamic changes. conclusions: mitopo shows the effect of interventions on mitochondrial oxygenation and provides additional information compared to standard monitoring and sto . introduction: traumatic asphyxia is a rare condition in which breathing and venous return is impaired due to a strong compression to the upper abdomen or chest region, and induces swelling, purplish red appearance, and petechiae around the face and neck. to our knowledge, there are no reports describing details of traumatic asphyxia including the clinical course and the therapeutic reactivity from cardiac arrest. we focused on cardiac arrest among all traumatic asphyxia patients treated at our hospital, and investigated their clinical features and therapeutic reactivity. methods: sixteen cases of traumatic asphyxia involved with our hospital between april and march were reviewed by using the pre-hospital activity record, medical record, and hyogo prefectural inspection record. these patients were divided into three groups. the first group had already cardiac arrest at the time of rescue from the trapped place (group a; cases). the second group became cardiac arrest after the rescue (group b; cases). the third group did not experience cardiac arrest (group c; cases). results: all cases had abnormal findings in skin or conjunctiva (table ) . total mortality rate reached %, but among cases of group a and b who resulted in cardiac arrest, there were cases with injury severity score or more and abbreviated injury scale in the chest or more. they had pneumothorax, flail chest, pericardial hematoma. seven of them restored spontaneous circulation, and two cases achieved neurologically full recovery. conclusions: there are some cases of traumatic asphyxia whose therapeutic reactivity is very good even after cardiac arrest, so it is important not to spare efforts for life support in such cases. rhythm and % witnessed arrest, five hundred ten ( %) patients had a good functional outcome at -months. physiological derangements were each negatively associated with outcome in bivariate analysis at the p < . level. a summary score of physiological derangements was included with potential confounders in the final regression model, and was independently associated with outcome with the chance of a good outcome decreasing by % for each increase of one physiologic derangement ( % ci . - . ). conclusions: uncorrected physiological derangements are independently and cumulatively associated with worse outcome after cardiac arrest. although causality cannot be established, it is reasonable to consider that the correction of physiological parameters may be an important step in the chain of survival after resuscitation. characteristics introduction: glan clwyd hospital (gch) was recently designated one of three cardiac arrest centres for wales. it has offered a / percutaneous coronary angiography (pci) service to a geographically dispersed north wales population of approximately , since june . prior to this, urgent coronary angiography was available on a more limited basis to patients requiring pci. the aim of this study was to investigate factors associated with hospital mortality after critical care admission following cardiac arrest. methods: retrospective review of the ward watcher critical care database at gch to identify patients who had undergone cpr in the hours prior to critical care admission in - . patients likely to have sustained ooha of cardiac aetiology (ooha-c) were identified from primary and secondary diagnoses and free text entry. data were subsequently analysed using excel and spss. the project was registered as a service evaluation with gch audit department. results: there were cardiac arrest admissions over this period, increasing from in - to in - . of these were ooha, of which were considered ooha-c. although ooha-c hospital mortality appeared to decrease over the time period ( %% to %), this was not statistically significant (p= . ). factors associated with survival to hospital discharge are presented in the tables below. on logistic regression, only pci and low ph within the first hours of critical care remained statistically significant (p= . and p< . respectively). conclusions: although we have been unable to make a distinction between patients presenting following stemi and nstemi, and appreciating a potential influence of selection bias, the significant association between pci and survival to hospital discharge supports the introduction of clinical pathways enabling pci access following ooha-c [ ] . chest radiography. [ ] here, we aimed to derive and validate rules to estimate p_max.lv using anteroposterior chest radiography (ches-t_ap), which is performed for critically-ill patients urgently needing determination of personalised p_max.lv. methods: a retrospective, cross-sectional study was performed with non-cardiac arrest adults who underwent chest_ap and computed tomography (ct) within h (derivation:validation= : ). on chest_ap, we defined cd (cardiac diameter), rb (distance from right cardiac border to midline) and ch (cardiac height, from carina to uppermost point of left hemi-diaphragm) (fig , ) . [ ] setting p_zero ( , ) at the midpoint of xiphisternal joint and designating leftward and upward directions as positive on x and y axes, we located p_max.lv (x_max.lv, y_max.lv). the coefficients of the following mathematically-inferred rules were sought: x_max.lv=a *cd-rb; y_max.lv=ß *ch+γ . (a : mean of (x_max.lv+rb)/cd; ß , γ : representative coefficient and constant of linear regression model, respectively ) . conclusions: evaluable echocardiographic records were reached in most of the patients. etco positively correlated with all parameters under consideration, while the strongest correlation was found between cimax and etco . therefore, cimax is a candidate parameter for real-time monitoring of haemodynamic efficacy of chest compressions during cpr. introduction: the uk resuscitation council has set out guidelines for management of patients post cardiac arrest [ ] . this is in line with european resuscitation council guideline. we set out to find if we are following the guideline. methods: we did a retrospective audit over the course of years looking at the data of patients who had in hospital and/or out of hospital cardiac arrest and after the return of spontaneous circulation were admitted to the intensive care unit (icu). we focused on whether the care they received was as per the standards set by the uk resuscitation council. results: we had in the hospital and out of hospital cardiac arrests; patients had less than minutes of cpr, had more than minutes cpr and patients the data was not recorded; patients needed more than minutes to reach from the site of arrest to the icu. the partial pressure of carbon dioxide was > . kpa in patients at two or more occasions. target map was not documented in patients; blood sugar target was not documented in patients and was not maintained within limits in patients. target temperature was not documented in patients. the withdrawal of treatment was not delayed for hours in patient out of . in patients neurological tests were not documented. multimodal assessment tools were not used in patient. electroencephalography and serum neuron specific enolase were not used to diagnose brain deaths as they were not available at our trust. patients were discharged, died in the icu and died in hospital after discharge from icu. conclusions: the audit reflected our local practice and showed that our mortality was in line with the acceptable limits; poor documentation of plan of care which posed problems in analyzing the care that these patients received; some of the parameters were not being maintained as set by uk resuscitation guideline. introduction: high-quality chest compressions (cc) with minimized interruptions are one of the most essential prerequisites for an optimal outcome of resuscitation. therapy of reversible causes of cardiac arrest often requires intra-hospital transportation (iht) during ongoing cpr. the present study investigated cc quality during transportation depending on the position of the provider. methods: paramedics were enrolled into a manikin study with four groups: a reference group with the provider kneeling beside manikin on the floor (group ), and groups performing cc during a simulated iht of meters: walking next to the bed (group ), kneeling beside the patient in bed (group , fig. ) or squatting above the patient in bed (group , figure ). indicators of cc quality were measured as defined in the erc guidelines (pressure point and depth, compression frequency, complete relief, sufficient pressure depth) [ ] . all paramedics performed cc during each scenario (group - ). results: there were no statistical differences in quality of cc between groups , and . notably, group performed significantly worse in respect to the proportion of cc with correct pressure point (p = . vs group ), correct cc depth (p= . vs. group , p= . vs. group , p= . vs. group ). the results are shown in table . conclusions: carrying out guideline-compliant cc [ ] during iht is feasible with multiple provider positions. based on the present results, kneeling or squatting position next to the patient ( figure and ) is recommended, whereas "walking next to the bed" while performing cc should be avoided. methods: a retrospective review of clinical notes was undertaken for patients admitted to icu following return of spontaneous circulation but whom remained comatose. this audit encompassed three-month periods before and after introduction of the care bundle in october . audit standards were assigned from target parameters documented in the bundle and reflected guidance from the cheshire and merseyside critical care network. results: patients were included in our audit; admitted prior to and admitted following implementation of the care bundle. in patients whom targeted temperature management was indicated, improved adherence to thermoregulation between - °c was observed ( vs %). significant improvements were since in the observance to target values for oxygen saturation ( vs . %, p= . ) and mean arterial pressure ( vs . %, p< . ) following the introduction of the care bundle. improved observance of ventilation targets was also seen; maintenance of p a co > . kpa ( vs %, p= . ) and tidal volumes < ml/kg ideal body weight ( to . %, p= . ). conclusions: the introduction of a post-cardiac arrest care bundle in our icu has improved care by providing discrete physiological targets to guide nursing staff and standardising management between clinicians. variations in care are associated with poorer patient outcomes [ ] and introduction of this bundle has reduced disparities in practice. array of cardiac diseases and reported survival rate is low in spite of advances in resuscitation and ems services. methods: single-centre retrospective study analyzed outcomes of ohca patients admitted to cardiac icu between .- . we studied demographic data, initial rhythm, type of cpr, comorbidities and various post admission diagnostic findings in order to identify their impact on survival. results: ohca comprised , % of all admissions. mean los was . days ( - ). mean age was , y ( - ), m: f ratio : and bystander cpr was performed in only % ohca patients. the most common initial rhythm was vf ( . %), followed by vt ( . %), pea was found in , % and asystole in . % of pt more than half of pt received adrenalin ( %) and defibrillation ( %) and only % required a temporary pacemaker. % of pt had an ecg consistent with mi after rosc, % underwent coronary angiography resulting in pci in % of cases. in pt ( %) therapeutic hypothermia protocol was performed. most ohca pt had hypertension ( %) and hyperlipidaemia ( %) as the most common risk factors followed by cardiomyopathy ( %), diabetes ( %) and cad ( %). only % had a preexisting significant valvular disease and the rest were extracardial comorbidities: chronic renal disease ( %), copd ( %) and cerebrovascular disease ( %). patients survived ( %) and gcs on admission was the only significant impact factor on survival along with comorbidities (mean gsc was in survivors vs. in deceased). interestingly, age, initial rhythm, troponin i level, ph and therapeutic hypothermia had no impact on survival. conclusions: our data demonstrate the importance of early onsite resuscitation as the most important factor of neuroprotection and outcome and puts an emphasis on the importance of cpr education for layman population. prediction of acute coronary ischaemia and angiographic findings in patients with out-of-hospital cardiac arrest j higny , a guédès , c hanet , v dangoisse , l gabriel , j jamart introduction: coronary artery disease (cad) is the leading cause of out-of-hospital cardiac arrest (ohca). however, diagnosis of acute coronary ischaemia (aci) remains challenging, particularly in patients without st-segment elevation on the post-resuscitation ecg. in this regard, a consensus statement recommends the implementation of a work-up strategy in the emergency room (er) to exclude noncoronary causes of collapse within hours. methods: retrospective single-centre study performed on consecutive patients with resuscitated ohca who underwent a diagnostic coronary angiography (ca). we present data on coronary angiograms for patients who underwent cardiac catheterization after resuscitation. afterwards, we sought to identify parameters associated with aci. results: st-segment elevation was noted in patients ( %). stsegment depression or t-wave abnormalities were noted in patients ( %). invasive coronary strategy allowed to identify an acute culprit lesion in cases ( %). patients with st-segment elevation underwent an immediate angioplasty for an acute coronary occlusion. patients without st-segment elevation underwent an ad hoc percutaneous coronary intervention for a critical lesion. stable cad was found in cases ( %) and a normal angiogram was found in only cases ( %) (figure ). conclusions: aci was the leading precipitant of collapse. stsegment elevation was highly predictive of coronary occlusion. in addition, a culprit coronary lesion was identified in nearly % of patients undergoing ca despite the lack of stsegment elevation. finally, our findings suggest that the identification of risk criteria may help to improve the recognition of aci after ohca. the prediction of outcome for in-hospital cardiac arrest (pihca) score e piscator , k göransson , s forsberg , m bottai , m ebell , j herlitz , t djärv figure. predictive value for classification into < % likelihood of favorable neurologic survival was . %. false classification into < % likelihood of favorable neurologic survival was . %. the phica score has potential to be used as an aid for objective prearrest assessment of the chance of favorable neurologic survival after ihca, as part of decision making for a dnar order. introduction: prognosis of survival in patients with cardiac arrest remains poor. during and after cardiopulmonary resuscitation, pathophysiological disturbances in relation with a cytokine storm, are described as "post-resuscitation" disease like a combination of cardiogenic and vasodilatory shocks. veno-arterial extracorporeal membrane oxygenation (va ecmo) allows to restore adequate perfusion but little is known about its effect on left ventricular (lv) function and about the role of cytokines. methods: this study was performed in an experimental model of cardiac arrest performed in groups of anesthetized and mechanically ventilated pigs. cardiac arrest was obtained by application of electrical current to epicardium inducing ventricular fibrillation. after a no-flow period of minutes, medical resuscitation with catecholamines and vasopressors was performed in "control" group while va ecmo was started in "ecmo" group and va ecmo in combination with cytosorb (extracorporeal blood purification therapy designed to reduce excessive levels of inflammatory mediators such as cytokines) was started in "ecmo-cyto" group. lv function was assessed with transthoracic echocardiography and arterial pressure with aortic pressure catheter. results: hemodynamic stability was obtained after ± and ± minutes in ecmo and ecmo-cyto groups, respectively. no return of spontaneous circulation was observed in control group. at minutes following cardiac arrest, lv area fractional change on short axis was normalized in ecmo and ecmo-cyto groups ( ± and ± %, respectively). vasopressor requirements were significantly lower in ecmo-cyto group than in ecmo group. conclusions: after cardiac arrest (no-flow) of minutes duration, va ecmo allowed complete lv recovery and hemodynamic stability within minutes of "post-resuscitation" disease. cytosorb added to va ecmo could contribute to reduce post-resuscitation vasodilatation. impact of rapid response car system on ecmo in out-of-hospital cardiac arrest: a retrospective cohort study m nasu , r sato , k takahashi introduction: extracorporeal life support (ecls) has been reported to be more effective than conventional cardio-pulmonary resuscitation (cpr). in ecls, a shorter time from arrival to implantation of extracorporeal membrane oxygenation (ecmo; door-to-ecmo) time has been reported to be associated with better survival rates. this study aimed to examine the impact of the physician-based emergency medical services (p-ems) using a rapid response car (rrc) on door-to-ecmo time in patients with out-of-hospital cardiac arrest (ohca to study the interest and the educational contribution in the short and medium term of medical simulation compared to a classical training. methods: cohort, prospective, observational, single-center, randomized study with control group including residents ( in anesthesia resuscitation and in emergency medicine). all benefited from a theoretical training with a reminder of the latest recommendations on the management of cardiac arrest and anaphylactic shock. they were randomized into groups and received practical training on a high-fidelity simulator for the management of either cardiac arrest (acc group) or anaphylactic shock (ca group). each group was evaluated at weeks (t ) and at months on two scenarios: refractory ventricular fibrillation (fv) scored on points and grade anaphylactic reaction (ra ) scored on points. each group served as the control group for the pathology in which they did not receive specific simulator training. the results are expressed on average with their standard deviations with "p" < . . introduction: simulation is a tool for improving the quality and safety of care, and its recognized as an essential method of evidence-based education. emergency medicine is a discipline in which there is a constant concern for the safety of patients. the emergency physician is often called upon to take charge of critical situations that use knowledge, know-how and knowledge as skills that must be mastered and whose theoretical learning alone is insufficient. methods: it´s a prospective study including residents in emergency medicine performing their specialty courses in emergency services and emergency medical assistance in the region of sousse from january to june . they were randomized into two groups: the one benefiting from a traditional education and the other from an education based on simulation sessions. the chosen scenario was the management of a cardiac arrest. a pre-test and a post-test were performed in both groups. results: we included emergency residents who did not receive specialized training in the management of cardiac arrest, there was a female predominance with an average age of , there was no significant difference regarding the pretest between the two groups with . there was no significant difference with respect to the pre-test score between the two groups . ± . / for the control group versus . ± . / for the simulation group. there was a significant progression after the course with an average posttest score of . ± . in the simulation group while this score was . ± . in the control group with a statistically significant difference (p < . ). conclusions: simulation learning has led to a better acquisition of cognitive knowledge by learners. the simulation is not intended to replace bed-based teaching, nor theoretical or faculty teaching, but it is an essential complement . in tunisia, the simulation must continue its current integration in the initial and continuous training of doctors. introduction: recent studies have shown that obesity and its related metabolic dysfunction exacerbates outcomes of ischemic brain injuries in some brain areas, such as the hippocampus and cerebral cortex when subjected to transient global cerebral ischemia (tgci). however, the impact of obesity in the striatum after tgci has not yet been addressed. the objective of this study was to investigate the effects of obesity on tgci-induced neuronal damage and inflammation in the striatum and to examine the role of mtor which is involved in the pathogenesis of metabolic and neurological diseases. methods: gerbils were fed with a normal diet (nd) or high-fat diet (hfd) for weeks and then subjected to min of tgci. hfd-fed gerbils showed the significant increase in body weight, blood glucose level, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol without affecting food intake. results: in hfd-fed gerbils, neuronal loss occurred in the dorsolateral striatum days after tgci and increased neuronal loss were observed cholesterol days after tgci; however, no neuronal loss was the in ndfed gerbils after tgci, as assessed by neuronal nuclear antigen immunohistochemistry and fluoro-jade b histofluorescence staining. the hfd-fed gerbils also showed severe activated microglia and further increased immunoreactivities and protein levels of tumor necrosis factor-alpha, interukin- beta, mammalian target of rapamycin (mtor) and phosphorylated-mtor in the striatum during pre-and postischemic conditions compared with the nd-fed gerbils. in addition, we found that treatment with rapamycin, a mtor inhibitor, in the hfd-fed gerbils significantly attenuated hfd-induced striatal neuronal death without changing physiological parameters. conclusions: these findings reveal that chronic hfd-induced obesity results in severe neuroinflammation and significant increase of mtor activation, which could contribute to neuronal death in the stratum following tgci. abnormal mtor activation might play a key role. associations between partial pressure of oxygen and neurological outcome in out-of-hospital cardiac arrest patients introduction: exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (ohca) patients following return of spontaneous circulation (rosc) but its effects on neurological outcome are uncertain and study results are inconsistent. methods: exploratory post-hoc substudy of the target temperature management (ttm) trial [ ] , including patients after ohca with rosc. the association between serial arterial partial pressures of oxygen (pao ) during hours following rosc and neurological outcome at months, evaluated by cerebral performance category (cpc), dichotomized to good (cpc - ) and poor (cpc - ), was investigated. in our analyses, we tested the association of hyperoxemia pao > kpa and hypoxemia pao < kpa, time weighted mean pao , (twm-pao ) (fig ) , maximum pao difference (Δ pao ) and gradually increasing pao levels ( . - . kpa) with poor neurological outcome. a subsequent analysis investigated the association between pao and a biomarker of brain injury, peak serum tau levels. results: patients were eligible for analysis. patients ( %) were exposed to hyperoxemia or hypoxemia after rosc (table ) . our analyses did not reveal a significant association between hyperoxemia, hypoxemia, twm-pao exposure or Δ pao and poor neurological outcome at -month follow-up after correction for co-variates (all analyses p= . - . ) (fig ) . we were not able to define a pao level associated with the onset of poor neurological outcome. peak serum tau levels at either or hours after rosc were not associated with pao . conclusions: hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first hours of hospitalization and was not significantly associated with poor neurological outcome after months or with the peak s-tau levels at either or hours after rosc. introduction: cerebral hypoperfusion may aggravate the developing neurological damage after cardiac arrest. near-infrared spectroscopy (nirs) provides information on cerebral oxygenation but its clinical relevance during post-resuscitation care is undefined. we wanted to assess the possible association between cerebral oxygenation and clinical outcome after out-of-hospital cardiac arrest (ohca). methods: we performed a post hoc analysis of a randomised clinical trial (comacare) where both moderate hyperoxia and high-normal arterial carbon dioxide tension (paco ) increased regional cerebral oxygen saturation (rso ) as compared with normoxia and low-normal paco , respectively. rso was measured from ohca patients with nirs during the first h of intensive care and neurological outcome was assessed using the cerebral performance category (cpc) scale at months after cardiac arrest. we calculated the median rso for patients with good (cpc - ) and poor (cpc - ) outcome and compared the results using the mann-whitney u test. we compared the rso over time with outcome using a generalised mixed model. finally, we added median rso to a binary logistic regression model to control for the effects of possible confounding factors. results: the median (interquartile range [iqr]) rso during the first h of intensive care was . % ( . - . %) in patients with good outcome compared to . % ( . - . %) in patients with poor outcome, p = . . we did not find significant association between rso over time and neurological outcome ( figure ). in the binary logistic regression model rso was not a statistically significant predictor of good outcome (or . , % ci . - . , p = . ). conclusions: we did not find any association between cerebral oxygenation during the first h of post-resuscitation intensive care and neurological outcome at months after cardiac arrest. fig. introduction: near-infrared spectroscopy (nirs) provides a noninvasive means to assess cerebral oxygenation during postresuscitation care but its clinical value is unclear. we determined the possible association between cerebral oxygenation and the magnitude of brain injury assessed with neuron-specific enolase (nse) serum concentration at h after out-of-hospital cardiac arrest (ohca). methods: we performed a post hoc analysis of a randomised clinical trial (comacare) comparing two different levels of carbon dioxide, oxygen and arterial pressure after ohca and successful resuscitation. we measured rso continuously with nirs from patients during the first h of intensive care. we determined the nse concentrations at h after cardiac arrest from serum samples using an electrochemiluminescent immunoassay kit. the samples were tested for haemolysis and all samples with a haemolysis index > mg of free haemoglobin per litre (n = ) were excluded from the analyses. we calculated the median rso for all patients and used a scatterplot and spearman's rank-order correlation to assess the possible relationship between median rso and nse at h. in addition, we compared the nse concentrations at h after cardiac arrest in patients with good (cerebral performance category scale [cpc] - ) and poor (cpc - ) neurological outcome at months using the mann-whitney u test. results: we did not find significant correlation between median rso and serum nse concentration at h after cardiac arrest, rs = - . , p = . (figure ). the median (iqr) nse concentration at h was . ( . - . ) μg/l and . ( . - . ) μg/l in patients with good and poor outcome, respectively, p < . . conclusions: we did not find any association between cerebral oxygenation during the first h of post-resuscitation intensive care and nse serum concentrations at h after cardiac arrest. the association between lactate, cerebral oxygenation and brain damage in post-cardiac arrest patients introduction: patients admitted to the intensive care unit (icu) after being successfully resuscitated from a cardiac arrest (ca) have a large cerebral penumbra at risk for secondary ischemic damage in case of suboptimal brain oxygenation. therefore, resuscitation during icu stay should be guided by parameters that adequately predict cerebral hypoxia. the value of lactate as resuscitation parameter may be questioned in post-ca patients since the brain critically depends on aerobic metabolism. we aimed to investigate the relationship between arterial lactate, cerebral cortex tissue oxygenation (scto ) by near infrared spectroscopy (foresight) and unfavorable neurological outcome at days (cpc score - ) methods: subanalysis from the neuroprotect post-ca trial. lactate values and scto were recorded hourly in post-ca patients during hours ttm and subsequent rewarming. results: in total paired lactate/ scto measurements were analysed. we found no correlation between paired lactate and scto² (fig. ) . moreover, temporary trends in lactate did not correlate with corresponding trends in scto during the same one-hour time interval (r²= . ) (fig ) . if lactate values above . mmol/l are considered to be abnormal, lactate could not adequately detect clinical important brain ischemia (scto < %): sensitivity % and specificity % (table , ). nevertheless, time weighted lactate at h (or . ; p . ), h (or . , p . ), h (or . ; p . ) and h (or . ; p . ) were inversely correlated with unfavorable neurological outcome at days (fig , ) . conclusions: although lactate was a marker of prognosis in post-ca patients, it should not be used to guide resuscitation since lactate values were not correlated with scto and changes in lactate do not correspond with changes in scto during the same time interval. simplified introduction: the aim of the study was to investigate whether simplified continuous eeg monitoring (ceeg) [ ] post-cardiac arrest can be reliably interpreted by icu physicians after a short structured training, and whether acceptable interrater agreement compared to an eeg-expert can be achieved. methods: five icu physicians received training in interpretation of simplified ceeg (fig ) consisting of lectures, hands-on ceeginterpretation, and a video tutorial -total training duration day. the icu physicians then interpreted simplified ceeg recordings. basic eeg background patterns and presence of epileptiform discharges or seizure activity were assessed on -grade rank-ordered scales based on a standardized eeg terminology [ ] . an experienced eeg-expert was used as reference. results: there was substantial agreement (κ . ) for eeg background patterns and moderate agreement (κ . ) for epileptiform discharges between icu physicians and the eeg-expert. sensitivity for detecting seizure activity by the icu physicians was limited ( %), but with high specificity ( %). among icu physicians interrater agreement was substantial (κ . ) for eeg background pattern and moderate (κ . ) for epileptiform discharges. conclusions: after a one-day educational effort clinically relevant agreement was achieved for basic eeg background patterns after cardiac arrest. assessment of epileptiform patterns was less reliable, but bedside screening by the icu physician may still be clinically useful for early detection of seizures. interpretation of simplified ceeg requires awareness of its limitations and support from an eeg-expert when clinically indicated. introduction: hypoxic-ischemic injury on head computed tomography (ct), which manifests with varying degrees of cerebral edema and loss of gray-white matter differentiation, is a poor prognostic sign after resuscitated out-of-hospital cardiac arrest that may influence early clinical decision-making. agreement among physicians on the presence of hypoxic-ischemic injury on early head ct is unknown. methods: we recruited faculty physician participants ( emergency medicine, critical care, neurocritical care, and general radiology; average . years of practice) across academic medical centers each with > admissions for resuscitated out-of-hospital cardiac arrest each year. participants, blinded to clinical context, reviewed unique head cts obtained within hours of cardiac arrest that were randomly selected from a local registry. a blinded neuroradiologist also reviewed all scans (gold standard). participants determined if hypoxic-ischemic injury was present on each ct, and agreement was determined using multi-and dual-rater kappa statistics with % confidence intervals. results: overall agreement among physicians regarding the presence of hypoxic-ischemic injury on head ct was fair (kappa . ; % ci, . - . ) with agreement consistent across most specialties (table ) . when compared to the neuroradiologist, individual physician agreement ranged widely, from poor (kappa . ) to substantial (kappa . ), with of physicians having fair or worse agreement compared to the gold standard interpretation. conclusions: the finding of hypoxic-ischemic injury on early head ct after cardiac arrest had high interobserver variability as interpreted by acute care physicians and general radiologists. pending the development of objective diagnostic criteria, clinicians should bear in mind the subjectivity and subtlety of cerebral edema or loss of graywhite matter differentiation soon after return of spontaneous circulation in these patients. figure ). baseline characteristics and differences between the wlst and no-wlst groups are shown in table . utilization of neuro-prognostication tests is shown in table . while ct and eeg were commonly employed, ssep and mri were used less frequently. basic multimodal neuroprognostication (arbitrarily defined as at least one ct or mri, plus eeg, plus ssep) was performed only in . % of all patients undergoing wlst but the rate increased significantly over six years (p< . ) and was higher in the time period after , compared to the one prior to ( figure ). this association remained significant after adjustment for confounders such as age, arrest rhythm, downtime, targeted temperature management, apache ii score and organ failure in a logistic regression model (p= . ). in an institution with access to a wide range of imaging and neurophysiology tests, mri and ssep remained underutilized but the rate of basic multimodal neuro-prognostication increased significantly over the study period, especially in the period after . introduction: although multiple reports using animal models have confirmed that melatonin appears to promote neuroprotective effects following ischemia/reperfusion-induced brain injury, the relationship between its protective effects and the activation of autophagy in cerebellar purkinje cells following the asphyxial cardiac arrest and cardiopulmonary resuscitation (ca/cpr) remains unclear. methods: rats used in this study were randomly assigned to groups as follows; vehicle-treated sham-operated group, vehicletreated asphyxial ca/cpr-operated group, melatonin-treated shamoperated group, melatonin-treated asphyxial ca/cpr-operated group, melatonin plus (+) p-pdot (the mt melatonin receptor antagonist)-treated sham-operated group and melatonin+ p-pdot-treated asphyxial ca/cpr-operated group. results: our results demonstrate that melatonin ( mg/kg, ip, time before ca and times after ca) significantly improved the survival rates and neurological deficits compared with the vehicle-treated asphyxial ca/cpr rats (survival rates ≥ % vs %). we also demonstrate that melatonin exhibited the protective effect against asphyxial ca/cpr-induced purkinje cell death. the protective effect of melatonin in the purkinje cell death following asphyxial ca/cpr paralleled a dramatic reduction in superoxide anion radical (o ·-), intense enhancements of cuzn superoxide dismutase (sod ) and mnsod (sod ) expressions, as well as a remarkable attenuation of autophagic activation (lc and beclin- ), which is mt melatonin receptor-associated. furthermore, the protective effect of melatonin was notably reversed by treatment with p-pdot. conclusions: this study shows that melatonin conferred neuroprotection against asphyxial ca/cpr-induced cerebellar purkinje cell death by inhibiting autophagic activation by reducing expressions of ros, while increasing of antioxidative enzymes, and suggests that mt is involved in the neuroprotective effect of melatonin in cerebellar purkinje cell death induced by asphyxial ca/cpr. introduction: fucoidan is a sulfated polysaccharide derived from brown algae and possesses various beneficial activities, such as antiinflammatory and antioxidant properties. previous studies have shown that fucoidan displays protective effect against ischemiareperfusion injury in some organs. however, few studies have been reported regarding the protective effect of fucoidan against cerebral ischemic injury and its related mechanisms. methods: therefore, in this study, we examined the neuroprotective effect of fucoidan against cerebral ischemic injury, as well as underlying mechanisms using a gerbil model of transient global cerebral ischemia (tgci) which shows loss of pyramidal neurons in the hippocampal cornu ammonis (ca ) area. fucoidan ( and mg/kg) was intraperitoneally administered once daily for days before tgci. results: pretreatment with mg/kg of fucoidan, not mg/kg fucoidan, attenuated tgci-induced hyperactivity and protected ca pyramidal neurons from ischemic injury following tgci. in addition, pretreatment with mg/kg of fucoidan inhibited activations of resident astrocytes and microglia in the ischemic ca area. furthermore, pretreatment with mg/kg of fucoidan significantly reduced the increased -hydroxy- -noneal and superoxide anion radical production in the ischemic ca area after tgci and significantly increased expressions of superoxide dismutase (sod ) and sod in the ca pyramidal neurons compared with the vehicle-treated-group. we found that treatment with diethyldithiocarbamate (an inhibitor of sods) to the fucoidan-treated-group notably abolished the fucoidanmediated neuroprotection in the ischemic ca area following tgci. conclusions: these results indicate that fucoidan can effectively protect neurons from tgci-induced ischemic injury through attenuation of activated resident glial cells and reduction of oxidative stress following increasing sods. thus, we strongly suggest that fucoidan can be used as a useful preventive agent in cerebral ischemia. the effects of cold fluids for induction of therapeutic hypothermia on reaching target temperature and complications-a sub-study of the tth study a holm , m skrifvars , fs taccone ). there was no difference in early bleeding incidences (fig ) . during late observation, ttm patients had fewer minor bleeding ( . % vs. %) and more intracranial bleeding ( . % vs. %; fig ) . adjusted calculated risk ratio for major bleeding (including intracranial) for ttm was . ( %ci . - . ) at baseline and . ( %ci . - . ) over time. conclusions: bleeding complications were common. although the risk ratio for major bleeding increased over time in ttm patients, residual and unmeasured confounding in addition to selection and detection bias may limit the clinical relevance of this finding. methods: patients with neurological deficit > by nhiss were included. the t°of the brain was recorded non-invasively using radiothermometer rtm- -res (russia). we measured t°in symmetric regions of left & right hemispheres, calculated the average t°of brain, fig. (abstract p ) . temperature of patients given and not given pre-icu fluids (table ) . conclusions: observed moderate brain t°heterogenecity in hp, marked increase brain t°heterogenecity in is & sharp decline of t°h eterogenecity in cci. supposedly, correcting the impairment of cerebral tb (increase or decrease t°) through physical (selective cerebral hypothermia, magnetic stimulation etc.) or pharmacological (sedation) can contribute to positive therapeutic results in is & cci. nonivasive radiothermometry of the brain can be an objective method of patients' condition evaluation & their rehabilitation potential. introduction: basilar artery stroke has a multitude of different presentations and may not be captured on plain computed tomography (ct). it can progress to severe disability, locked in syndrome and death [ ] . with the advent of thrombolytic and endovascular therapies, prompt diagnosis can change the outcome. we present a case of basilar artery stroke, which was heralded by tongue spasticity and dysarthria, indicative of pseudobulbar palsy. methods: case reviewed with consent. a literature search was conducted using pubmed and medline. results: a -year-old presented with pulmonary oedema and hypertension. he was transferred to our intensive care unit for treatment of a suspected anaphylaxis. his marked lingual swelling was associated with dysarthria. glyceryl-trinitrate and labetalol infusions were started for hypertension. he developed left sided weakness and deteriorated over several days to the point that he could only move his right foot (table ) . magnetic resonance imaging (mri) showed midbrain ischaemia and angiogram showed no flow in the basilar artery (fig , ) . conclusions: common presenting features of basilar artery occlusion include dysarthria, vertigo, vomiting, headache and motor defects; these may evolve gradually or be intermittent [ , ] . presentation with pseudobulbar palsy is described in early literature [ ] . delayed recognition of the stroke led to aggressive treatment of hypertension, potentially compromising perfusion to the penumbral area [ , ] . this case highlights the need for a wide index of suspicion with posterior strokes. consent: informed consent to publish has been obtained from the patient prognosis is related to gcs < or = on admission (p = . ) and to malignant cerebral edema (p = . ). conclusions: our study has shown some predictive factors closely related to mortality and morbidity in patients with acute ischemic stroke. gcs at admittance < or = and onset of malignant cerebral edema lead to a worst prognosis at discharge from nicu. coherence analysis of cerebral oxygenation using multichannel functional near-infrared spectroscopy evaluates cerebral perfusion in hemodynamic stroke tj kim table ). in addition, severe stroke patients were more likely to have higher phase coherence in interval iii (p = . ). conclusions: our results demonstrated that the higher phase coherence of oxyhb in myogenic signal, which was originated locally from smooth muscle cells in brain was related to impaired cerebral perfusion. this suggests that monitoring cerebral oxygenation using fnirs could be a useful noninvasive measuring tool for evaluating impaired cerebral autoregulation in stroke patients. is esmolol associated with worse outcome at the acute phase of ischemic stroke that receives thrombolysis? introduction: ischemic stroke patients experienced frequent early neurological deterioration (end) events. since ischemic stroke has also been shown as inflammatory disease, the neutrophil-tolymphocyte ratio (nlr) may associated with end events. however, the direct study regarding this association has not been addressed. poor grade sah, use of vasopressors, mechanical ventilation, intracranial pressure monitoring, external ventricular drainage, blood transfusions and renal replacement therapy were all more frequent among nonsurvivors (all p< . ). mortality was also higher with initial lactate above mmol/l, in those admitted to public hospitals and when admission to icu was delayed more than hours after ictus. after adjusting for common predictors (age, gender and wfns) saps non-neuro, sofa non-neuro, early vasopressor use and admission to a public hospital were independently associated with hospital mortality. moreover, the area under the curve for prediction of mortality with saps , sofa and wfns was . ( figure ). hospital, austria. the association of intensity and duration of intracranial hypertension episodes with -month glasgow outcome score (gos) was visualized using the methodology introduced by güiza et al. [ ] . results: in both cohorts, it could be demonstrated that the combination of duration and intensity defined the tolerance to intracranial hypertension, and that a semi-exponential curve separated episodes associated with better outcomes from those associated with worse outcomes. the association with worse outcomes occurred at a lower pressure-time burden than what has been previously observed in patients with tbi. nevertheless, the percentage of monitoring time spent by every patient in the zone associated with poor gos was independently associated with worse -month neurological outcome, even after correcting for age and fisher score ( introduction: apnea test is an essential component in the clinical determination of brain death, but it may incur a significant risk of complications such as hypotension, hypoxia and even cardiac arrest [ ] . we analyzed the risk factors associated with failed apnea test during brain death assessment in order to predict and avoid these adverse events. methods: medical records of apnea tests performed for brain-dead donor between january and january in our institution, were reviewed retrospectively. age, gender, etiology of brain death, use of catecholamine and results of arterial bleed gas analysis (abga), systolic/diastolic blood pressure (sbp/dbp), mean arterial pressure (map) and central venous pressure (cvp) prior to apnea test initiation were collected as variables. a-a gradient and pao /fio were calculated for more precise assessment of the respiratory system. in total, cases were divided into a group which was completed apnea test and the other which was failed the test. introduction: tunisia has already suffered recurrent outbreaks since . outbreak started relatively earlier this year. we were interpellated by the frequency of neuroinvasive presentation of the disease. methods: we report a case series of patients presented to icu with niwnd. results: we report cases of niwnd with different severe presentations overlapping neurological manifestation including encephalitis (n= / ), meningitis (n= / ) and flaccid paralysis (n= / ). almost all patients live in the locality of sousse. six patients presented a long course of isolated fever before developing neurological signs. cerebrospinal fluid was consistent with encephalitis within the patients. cerebromedullar mri identified brain lesions (n= / ), myelitis (n= / ) and polyradiculoneuritis (n= / ).three patients had electromyography for flaccid paralysis showed diffuse axonal polyneuropathy with motoneuron involvement. ten cases had a positive wnv igm antibody and nine had a positive wnv igg antibody in serum. urine polymerase chain reaction was positive for wnv in / patients. ten patients were mechanically ventilated. all patients were managed symptomatically. two received high doses of methylprednisolone for days, one patient received polyclonal immunoglobulin intravenous and one patient had plasmapheresis. two patients died consecutive to brainstem lesions. two patients recovered significantly and discharged with no complications. five other patients evolved to persistent flaccid paralysis with a minimal consciousness state and weaning difficulties requiring tracheostomy. the last remaining patient is still evolving. conclusions: modification of the regional climatic conditions accounted probably for the early outbreak of niwnd. this initial case series displays the severity and the poor outcomes of niwnd with higher incidence compared to past epidemics. noninvasive estimation of intracranial pressure with transcranial doppler: a prospective multicenter validation study c robba , c fig. ], mean bias was - . mmhg (limits of agreement are ± sd . mmhg). . % measures were outside the limit of agreement in the overall population. however, when icp was high, % of measures were out of the limit of agreement. the auc [ fig. introduction: surgical treatment of aortic aneurysm needs extracorporeal circulation (ecc), aorta clamp and hypothermia, and it is often related to poor systemic perfusion and blood flow velocity. one of the main concerns of intensive care team is to prevent secondary neurological injury after long time without blood flow pulsatility, such as brain edema and seizure. the most common parameters for neuromonitoring would be intracranial pressure and eeg, however, for non-neurological patients this information is unusual and prevents optimal management. methods: we aimed to assess brain compliance and neurological condition of icu patients on immediate post-operative recovery of bentall-de bono procedure and/or other aortic aneurysm surgical treatment using a novel non-invasive intracranial pressure (icp) device. this device uses mechanical displacement sensor capturing extracranial continuous volumetric variation of the skull and this information proportionally reflects intracranial dynamic [ ] . results: twenty patients were included in this study. ecc mean time was minutes for patients and only one did not need it. eleven presented altered icp curves with poor brain compliance (p /p ratio > . ) assessed by icp curve morphology analysis. volemic optimization and neuroprotective measures were taken based on this icp information for acute case management. among these patients with altered icp curves, eight were discharged from icu with good clinical condition and glasgow coma scale of . overall mortality rate was six out of twenty ( %) and three of these had altered icp curves. conclusions: brain monitoring of cardiovascular post-operative patients is important to prevent secondary neurological complications and can be a helpful tool for neuroprotective acute management on icu. the technique supplies electrical current to muscle, combined with passive cycling. prior to a clinical trial, we first investigated the effects of one session of fes in healthy volunteers. methods: healthy male volunteers (n= ) were recruited. the participants had their postural sway assessed on a pressure sensitive board, and measurement of maximal inspiratory pressure (mip). ultrasounds were taken assessing thickness of the quadriceps and rectus abdominis. they performed minutes of supine passive cycling, with fes supplying the lower limbs and abdomen. after a minute rest, the tests were repeated. a further participants performed just the initial baseline tests, to help assess muscular factors affecting balance and sway. results: the current needed for palpable contraction was significantly correlated to weight in the abdomen (r= . , p< . ) and quadriceps (r= . , p< . ). current required to stimulate the abdominal muscles was also correlated to depth of the subcutaneous fat layer (r= . , p< . ) and echogenicity of the muscle (r= . , p= . ). pre-cycling, left and right vastus lateralis thickness inversely correlated to postural sway in the antero-posterior (r=- . , p< . ) plane. compared to pre-cycling, postural sway in the antero-posterior and lateral planes increased significantly after cycling. there was a significant decrease in mip after cycling and greater reductions in mip were found in participants who had thinner rectus abdomni. conclusions: sway at baseline is related to quadriceps thickness, which atrophies during critical illness, and could worsen balance. mip is reduced during fes and the severity of reduction is related to the thickness of the abdominal wall muscles at baseline, suggesting that fes can fatigue the diaphragm and abdominal muscles. in awake healthy volunteers, fes is a safe, comfortable technique. introduction: in most cases postoperative cognitive dysfunction (pocd) is transient, but still some patients suffer from persistent cognitive impairment which is associated with increased length of hospital stay, early withdrawal from labor market and higher mortality. available data on the prevalence of pocd after cardiac surgery is very diverse from % to % upon discharge and up % months after surgery. we aimed to investigate the prevalence of short-term and long-term pocd after off-pump coronary artery bypass grafting (cabg) surgery. methods: psychometric testing was performed in (mean age . ± . ) patients before, days and months after the surgery. we used following tests to assess cognitive capacity: auditory verbal learning test (avlt), digit span test (dst), digit-letter substitution test (dlst), stroop's test and trail making test (tmt). a decline in comparison to preoperative test results for % or more in two or more tests was declared as pocd. results: the prevalence of pocd after days was . % ( patients) and . % ( patients) after months. when comparing patients who developed pocd with those who did not we found the former were older ( . ± . vs . ± . years; p< . ), had lower education level ( . ± . vs . ± . years; p< . ) and had longer surgery duration ( . ± . vs . ± . minutes; p< . ). the most affected cognitive domains were long term memory (avlt) and executive function (tmt) and least affectedworking memory (dst) and selective attention (stroop's test). conclusions: in our prospective study the prevalence of long-term pocd after cardiac surgery was slightly less ( . %) in comparison to available data (from % to %). it might be due differences in psychometric testing and interpretation of its results among authors. advanced age, low cognitive reserve and long duration surgeries are linked with higher incidences of pocd. introduction: postoperative cognitive dysfunction (pocd) is a common and widely described phenomenon in surgical patients. advanced age, major surgery, certain general anesthetics, genetic factors, sleep deprivation and other factors were described as contributing factors to pocd. the hospital stay itself is a major 'social' trauma for patients; social isolation, sleep deprivation and changes in daily regimen may effect neurocognitive behavior of patients. in this trial we tried to assess the link between pocd and the length of hospital stay in cardiac surgery patients. methods: patients who underwent 'off-pump' coronary artery bypass grafting (cabg) surgery selected for this trial. neuropsychological testing was performed prior to the operation and upon discharge. we used auditory verbal learning test (avlt), digit span test (dst), digit-letter substitution test (dlst), stroop test and trail making test (tmt). a % or more decline in two or more tests in comparison to preoperative test results was declared as pocd. patients were allocated into two groups according to the length of hospital stay: the short-stay group (group ) included patients (n= ) who were discharged on the th day after surgery or earlier and the long-stay (group ) group consisted of patients (n= ) who were discharged on the th day after surgery or later. patients received similar anesthesia, postoperative care and were operated by the same surgical team. reasons for prolonged duration of hospital stay were mainly surgical. results: patients ( . %) in group and patients ( . %) in group had pocd upon discharge (p< . ). mean length of hospital stay were ± . and ± . days in group and group patients respectively (p< . ). conclusions: prolonged length of hospital stay increased the prevalence of pocd in our trial. studies with various types of surgical procedures and larger patient populations needed to further understand the effect of length of hospital stay to pocd. the influence of multiple trauma with head trauma on posttraumatic meningitis: a nation-wide study with hospital-based trauma registry in japan introduction: posttraumatic meningitis is one of severe complications and results in increased mortality and longer hospital stay among head trauma patients. however, it remains unclear whether there is a difference in the incidence of post-traumatic meningitis due to single traumatic brain injury (tbi) and multiple trauma including head injury. methods: this study was a retrospective observational study during years we included trauma patients registered in japanese trauma data bank whose head ais score was > in this study. multivariable logistic regression analysis was used to assess potential factors associated with posttraumatic meningitis such as csf fistula, skull base fracture, type of injury that divided into single tbi and multiple trauma. introduction: the aim of this study was to determine if regional cerebral oxygenation (rsco ) can be used as an indicator of tissue perfusion in icu patients with tbi [ , ] , and to determine the prognostic value of cerebral oxygenation rsco in survival prediction. methods: patients were enrolled retrospectively from january through july in the icu of derince kocaeli training hospital. patients with trauma patients and traumatic braine injury patients who were admitted to the icu from the emergency room were included in the study. the sedation levels of the patients were followed up with bis. the rsco , bis was taken as well as blood lactate level, mean arterial blood pressure and cardiac output at baseline time, , , , and hours. results: no significant difference was also detected between the value of rsco in all patients . it was average sco (right) . ± . and average rsco (left) . ± . . conclusions: cerebral regional oxygen saturation might be helpful as one of the perfusion parameters in patients with tbi but it could have no prognostic value in mortality prediction. however, further studies with larger sample size are still needed to validate these results. introduction: tbi in elderly is an increasingly cause of admission in icu. data regarding management and prognosis of these patients are lacking. validated prognostic models refer to younger patients and do not adequately consider the influence of pre-injury functional status, which often compromises with aging. frailty has been defined as a state age-related of increased vulnerability and decline in autonomy of daily life activity. aim of the study is to evaluate the impact of frailty on outcome in tbi elderly patients. methods: moderate and severe tbi patients > years, admitted in neuroicu from january to may , were prospectively enrolled. data of age, comorbidity, glasgow coma scale (gcs), pupils' reactivity, ct scan characteristics, neurosurgical intervention and gose (extended glasgow outcome scale) at -months were collected. frailty status was measured by clinical frailty scale (cfs) [ ] and patients were divided as frail (cfs> ) and not frail (cfs< ). bad outcome was defined as gose< . results: ( %) of the studied patients were frail. frailty was not related to age. frail patients had more comorbidities and worse pupils' reactivity at admission (table ) . other variables did not differ between groups. in univariate analysis neurological diseases, gcs, tsah (traumatic subarachnoid haemorrhage), compressed/absent basal cisterns, non-reactive pupils and cfs were significantly associated to bad outcome. in multivariate analysis only gcs and cfs remained associated to bad outcome ( table ) . conclusions: pre-injury frailty is strongly associated to outcome in tbi elderly patients. the age of the patients was . ± . years. patients were operated on for intracranial traumatic ( cases) and non-traumatic hematomas ( ), brain tumors ( ) and the need for plastic of postoperative skull defects ( ). general endotracheal total intravenous anesthesia with fentanyl, propofol, rocuronium, or tracrium was used. after tracheal intubation, - nerves were blocked (e.g., supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, great auricular, greater and lesser occipital nerves), depending on the surgical site. . - . % ropivacaine was used. for blockade of one nerve used . - . ml of local anesthetic. fentanyl was applied on section of a periosteum, dura matter and at inefficiency of blockade of nerves. anesthesiology monitoring included hr, ecg, spo , nib, respiratory parameters, eeg (csi), body temperature, blood glucose and lactate levels. in and - hours post-surgery, the intensity of pain was ranked by alert patients using vas. results: the volume of local anesthetic for blockade in one patient was . ± . ml. in ( . %) from patients, an additional fentanyl injection was required to skin incision due to an increase in blood pressure and heart rate by % of the baseline values, and an increase in csi until un. patients available to productive contact in hours post-surgery ranked the pain by vas at ( ; ) point, and in - hours post-surgery ranked it at ( ; ) p. conclusions: at patients with craniotomies scalpe-block with lowvolumes of a ropivacaine showed high efficiency ( . %). were transferred to hospital ward or ( . %) to the center of intensive nursing care; ( . %) went to the surgical recovery room. acute renal failure, hypernatremia and hyperphosphatemia were independent predictors of mortality as described in table . conclusions: hypernatremia and hyperphosphatemia were independent predictors of mortality in critically ill patients. introduction: the strong ion difference (sid) is essential for the assessment of acid-base equilibrium, thus requiring an accurate measurement of plasma electrolytes. currently there is no gold standard for electrolyte measurements and sid computation. differences in electrolyte values obtained with point-of-care (poc) and central laboratory (lab) analyzers have been reported [ , ] . in previous studies [ , ] we have shown that changes in pco induce electrolyte shifts from red blood cells to plasma (and vice versa), yielding variations in sid. aim of the present in-vitro study was to induce sid changes through acute changes in pco and compare values of electrolytes and sid obtained with poc and lab techniques. methods: blood samples from healthy volunteers were tonometered (equilibrator, rna medical) with gas mixtures at fractions of co (fco ) of , , and %. electrolytes were measured quasisimultaneously with a poc analyzer (abl flex, radiometer) and a routine lab method (cobas ise, roche). for both techniques a simplified sid was computed as sodium + potassiumchloride. results: bland-altman analysis of sid calculated with poc and lab showed a proportional bias (slope = . , r = . , p < . ), indicating a variable agreement between methods according to the average sid value (fig. ) . sid values measured with poc and lab at different fco differed significantly (p< . , fig. ) . a similar discrepancy was observed for chloride (p < . , fig. ), while sodium (p= . ) and potassium (p= . ) were similar. conclusions: sid measured with poc and lab differed significantly, mainly due to a variable discrepancy in chloride. our findings suggest that our poc analyzer is superior to the lab in measuring electrolytes and thus compute sid. introduction: this study evaluated the safety of half dose insulin (hdi) versus standard dose insulin (sdi) for the treatment of hyperkalemia in a medical intensive care unit (micu) population with renal insufficiency. recent emergency medicine data demonstrated a lower incidence of hypoglycemia in patients with renal insufficiency when hdi was used for the treatment of hyperkalemia [ ] . there is limited data describing the safety of hdi in a micu population with renal insufficiency. methods: this was a retrospective, chart review of patients admitted to the micu with a diagnosis of aki and/or ckd stage - with a serum potassium ≥ . meq/l from january to september . sdi is defined as units of regular iv insulin and hdi as units. the primary outcome was the incidence of hypoglycemia within hours of insulin administration. secondary outcomes included severe hypoglycemia and change of serum potassium after insulin administration. results: a total of patients were screened and were included for analysis. the incidence of hypoglycemia occurred in / patients ( . %) and / patients ( . %) who received sdi and hdi, respectively. one patient in the sdi group and two patients in the hdi group developed severe hypoglycemia. the mean decrease in serum potassium after insulin administration was . meq/l in both groups. patients in the hdi group who were re-dosed with units of regular insulin did not have any hypoglycemic events. conclusions: in a micu population with renal insufficiency, sdi and hdi regimens appear safe and effective for the treatment of hyperkalemia. introduction: sepsis and septic shock are common causes of admission in the intensive care unit with a high mortality rate [ , ] . hence, electrolyte disturbances are common in this group of patients. acute hypernatremia is one of the multiple features of homeostasis disturbances and available data in the literature suggest that its incidence can reach % [ , ] . (fig , ) . the main source of sepsis was pneumonia with affected patients ( . %). conclusions: hypernatremia is significantly associated with higher mortality in septic patients. (abstract p ) . the outcome versus the sodium levels higher in the group - % vs . % (p= . ). there were no significant differences between the groups in length of stay in the icu. in group , there was an increase of serum phosphorus level and in the group the tendency to decrease. however, statistically significant differences were obtained only on the nd day after surgery . ± . mmol/l (group ) vs . ± . mmol/l (group ) (p= . ). the roc curve was constructed to assess the predictive significance of serum phosphorus levels (fig. ) . auc was . ; % ci . - . ; p= . ; sensitivity . %, specificity . %. the kaplan-meier survival analysis (fig. ) introduction: the rate of extubation failure might be higher in obese patients than in non-obese patients. effect of obesity on mortality is controversial [ , ] (obesity paradox). several pathophysiological changes contribute to an increase of respiratory complications [ ] . we sought to identify incidence of extubation failure in obese and non-obese patients. methods: the primary endpoint of this post-hoc analysis of a prospective, observational, multicenter study [ ] performed in intensive care units was extubation failure, defined as the need for reintubation within hours following extubation. only patients with body mass index (bmi) recorded were included. results: between december , and may , , among the patients with bmi available undergoing extubation, obese patients ( %) and non-obese patients ( %) were enrolled. extubation-failure rate was . % ( / ) in obese patients, and . % ( / ) in non-obese patients (p= . ). delay of reintubation did not differ between obese and nonobese patients (figure ). length of intubation > days was significantly more frequent in obese patients ( / , %) than in non-obese patients ( / , %, p< . ). precautions to anticipate extubation failure were more often taken in obese patients ( / , %) than in non-obese patients ( / , %, p< . ). spontaneous breathing trial (sbt) characteristics differed between obese and non-obese patients (table ) . physiotherapy was more often used in obese patients ( / , %) than in non-obese patients ( / , %, p= . ). conclusions: incidence of extubation failure did not differ between obese and non-obese patients. in obese patients, clinicians anticipate more a possible extubation failure, delaying the moment of extubation, performing more physiotherapy and providing an optimal sbt. introduction: in the acute phase of critical illness, growth hormone (gh) resistance develops, reflected by increased gh and decreased insulin-like growth factor-i (igf-i), mimicking fasting in health. the epanic rct observed fewer complications such as muscle weakness and faster recovery with accepting a macronutrient deficit in the first icu week, as compared with early full feeding [ , ] . we characterized its impact on the gh axis in relation to the risk of acquiring muscle weakness. methods: in this epanic rct sub-analysis, for matched patients per group, and all patients assessed for muscle weakness (n= ), serum gh, igf-i, igf binding protein (igfbp ) and igfbp were measured upon icu admission and at day or the last icu day for patients with shorter icu stay (d /ld). for matched patients per group, gh was quantified every min between pm and am, and deconvolved to estimate gh secretion. groups were compared with wilcoxon test or repeated-measures anova. associations between changes from baseline to d /ld and muscle weakness were assessed with logistic regression analysis, adjusted for baseline risk factors, baseline hormone concentrations and randomization. results: in the fully fed group gh, igf-i and igfbp increased, whereas igfbp decreased from admission to d /ld (all p< . ). accepting an early macronutrient deficit prevented the rise in gh and igf-i and the decrease in igfbp (all p< . ) but did not affect igfbp , whereas basal, but not pulsatile, gh secretion was lowered (p= . ). a stronger rise in gh and igf-i was independently associated with a lower risk of acquiring muscle weakness (or ( %ci) per ng/ml change . ( . - . ) for gh; . ( . - . ) for igf-i). conclusions: accepting an early macronutrient deficit suppressed basal gh secretion and reduced igf-i bioavailability during critical illness, which may counteract its protection against muscle weakness. introduction: aim of the study was to relate hypokalemia (hypok) and hypoglycemia as diabetic ketoacidosis (dka) treatment complications and precocious insulin interruption also use of sodium bicarbonate with length of stay (los) in intensive care unit (icu). methods: analysis of retrospective cohort study data of patient (pt) treated for dka at icu of hospital kaunas clinics of lithuanian university of health sciences during - has been carried out. serum kalemia, glycaemia; rate of episodes of hypok, hypoglycaemia and precocious insulin interruption; use of sodium bicarbonate, in relation with los in icu were analysed. spss . was used for statistic calculations. traits evaluated as significant at p< . . results: at the beginning of dka treatment hypok ( . ± . mmol/l) was recorded in / ( %) pt. due to disregarding of blood ph ( . - . ( . ± . ) kalemia was falsely misinterpreted as "normo-" or "hyperkalemia" . - . ( . ± . mmol/l) in of ( %) pt, as normo-and hyperkalemia thus not treated and complicated by hypok additionally in / ( %) pt. in hypok los in icu was . ± . vs . ± . h, p< . . insulin use has caused hypoglycaemia ( . - . ( . ± . mmol/l)) in / ( %) pt, los in icu . ± . vs . ± . h, p< . . insulin use was interrupted in case of normo -and hypoglycaemia with still persisting ketoacidosis in / ( %) pt, los in icu was found to be . ± . vs . ± . h, p< . . sodium bicarbonate was given for symptomatic treatment of acidosis during the first h of dka in / ( %) pt with stable hemodynamic: hco buffer has increased ( . ± . - . ± . mmol/l), p< . , but ketoacidosis has still persisted, los in icu was . ± . vs . ± . h, p< . . conclusions: hypok ( %), hypoglycemia ( %), precocious interruption of insulin use ( %) have prolonged los in icu almost twice. symptomatic treatment of ketoacidosis with sodium bicarbonate ( / pt) didn't control it and has prolonged los in icu. introduction: cystathionine-γ -lyase (cse), a regulator of glucocorticoid (gc)-induced gluconeogenesis [ ] , correlates with endogenous glucose production in septic shock [ ] . the hyperglycemic stress response to noradrenaline (noa) is mediated by the kidney [ ] and less pronounced with low cse [ ] . gc receptor (gr)-mediated gene expression is differentially regulated: the gr monomer is considered to repress inflammation, and gc side effects are attributed to the gr dimer; recent reports challenge this view [ ] . gc-induced gluconeogenic gene expression is reduced in gr dimerization deficient (grdim) mice [ ] . the aim of this study is to investigate renal cse expression and systemic metabolism in grdim and grwt mice in a resuscitated model of lps-induced endotoxic shock. methods: anesthetized grdim (n= ) and grwt (n= ) mice were surgically instrumented, monitored, resuscitated and challenged with lps. noa was administered to maintain map and c glucose was continuously infused. h after lps, cse expression was determined via immunohistochemistry of formalin-fixed paraffin sections (n= p.gr.). results: grdim required . -fold more noa than grwt and had . fold higher glucose and . -fold higher lactate h after lps. this was concomitant with elevated endogenous glucose production ( -fold), % lower glucose oxidation and . -fold higher renal cse expression in grdim. conclusions: increased cse expression together with higher glucose production (confirming [ , ] ) and glucose levels in grdim mice suggest an association that may link cse to gc signaling. the higher noa administration in grdim mice could contribute to these effects. introduction: to achieve safe glycemic control in critically ill patients frequent blood glucose (bg) measurements and according titration of insulin infusion rates are required. automated systems can help to reduce increased workload associated with diabetes management. this bi-centric pilot study combined for the first time an intraarterial glucose sensor with a decision support system for insulin dosing (sgcplus system) in critically ill patients with hyperglycemia. methods: twenty-two patients ( females, males, with preexisting diabetes mellitus, age . ± . years, bmi . ± . kg/ m , creatinine level . ± . mg/dl, saps (simplified acute physiology score) . ± . , tiss- (therapeutic intervention scoring system) . ± . who were equipped with an arterial line and required iv insulin therapy were managed by the sgcplus system during their medical treatment at the intensive care unit. results: sgcplus-based bg determinations were performed and . ± . sensor calibrations per day were required. sensor glucose readings correlated well with reference bg (figure ). mean treatment duration was . ± . days. time to target was ± min ( - mg/dl) and ± min ( - mg/dl). mean blood glucose was ± mg/dl with seven blood glucose values < mg/dl. mean daily insulin dose was ± u and mean daily carbohydrate intake ± g /day (enteral nutrition) and ± g/day (parenteral nutrition). acceptance of sgcplus suggestions was high (> %). the novel intraarterial glucose sensor demonstrated to be highly accurate. the sgcplus system can be safely applied in critically ill patients with hyperglycemia and enables good glycemic control. introduction: we aimed to assess the effect of frailty as assessed by clinical frailty scale (cfs) and karnofsky performance score (kps) on critical care (cc) and hospital mortality in this group at a nonspecialist tertiary critical care unit. methods: patients admitted to critical care were identified from our electronic database by screening for liver disease or cirrhosis in the admission diagnoses. those with an aetiology of liver disease other than alcoholic liver disease (ald) were excluded. data was collected on patient demographics, length of stay, status at discharge from critical care and hospital and cfs. kps was also calculated where sufficient in-formation was available in the medical record. data was analysed using logistic regression multivariate analysis with stata software. [ ] . results: tg diagnosis criteria and severity grading criteria for acute cholangitis and acute cholecystitis were judged from numerous validation studies as useful indicators in clinical practice and adopted as tg diagnostic criteria and severity grading without any modification. provide initial treatment, such as sufficient fluid replacement, electrolyte compensation, and intravenous administration of analgesics and full-dose antimicrobial agents, as soon as a diagnosis has been made. in new flowchart for the treatment of acute cholecystitis (ac) in the tg , grade iii ac was indicated for gallbladder drainage, but some grade iii ac can be treated by laparoscopic cholecystectomy (lap-c) at advanced centers with specialized surgeons experienced in this procedure and for patients that satisfy certain strict criteria. we also redefine the management bundles for acute cholangitis and cholecystitis. introduction: c-acetate breath tests provide a non-invasive assessment of gastric emptying [ ] and could, hence, be used to judge tolerance to enteral nutrition. result values like t (time for % absorption) correlate with scintigraphic measurements. the data evaluation is based on model equations like the β -exponential function (bex) [ ] . it considers a mono-phasic breath gas response. this may not be the case during critical illness, which could reduce precision too low for a reliable personalized assessment [ ] . methods: we recently developed an evaluation of irregular gastric emptying patterns, which separates absorption from post-absorptive distribution and retention of tracer and from the terminal respiratory release of the oxidized tracer [ ] . using breath test data of icu patients (mean saps +/- ) the precision of this approach was compared with a bex analysis to explore how often an extended analysis is warranted and whether it improves the reliability of estimates. results: patients had a release profile consisting of series of peaks with a periodicity of - min. a first dominant peak carries about % of the released moiety, as reported [ ] for controls. for these patients the precision in t for the bex approach was +/- % of that observed for the new approach. for the other patients, the secondary peaks had a similar periodicity but were more pronounced, indicating persisting peristaltis, which has been linked to tolerance to enteral nutrition [ ] . the bex approach achieved a precision of +/- % relative to the new one, challenging its applicability for these patients. introduction: clinical scoring systems used to prognosticate the severity of acute pancreatitis (ap), such as apache ii, are cumbersome and usually require hours or more after presentation to become accurate, at which time the window for early therapeutic intervention has likely passed. sirs at presentation is sensitive but poorly specific for severe ap. we postulated that sirs and accompanying hypoxemia would specify at presentation patients with ap who have severe inflammation and are at risk for clinically severe disease. methods: patients with ap who had sirs and hypoxemia at presentation were enrolled in an open-label study evaluating the safety and efficacy of cm -ie, a calcium release-activated calcium (crac) channel inhibitor (nct ). hypoxemia was defined as an estimated pao < mm hg calculated using a log-linear equation and the spo on room air at the time of presentation. a contrastenhanced computed tomography (cect) was performed at presentation and a cbc with differential, d-dimer and crp were analyzed daily. the cect was read by a blinded central reader who assessed the degree of inflammation using the balthazar scoring system (table ) . results: patients, seven men and six women, have been randomized in the study. the mean estimated pao at presentation was mm hg. patients had sirs criteria present and the other patients had sirs criteria present. the median value for age was . (iqr - ), initial neutrophil-lymphocyte ratio (nlr) . ( . introduction: to investigate whether circulating immune profiles were able to serve as early biomarkers in predicting persistent organ failure (pof methods: thirty-nine patients with predicted severe acute pancreatitis (psap) and healthy control subjects were prospectively enrolled in our study. we measured the expression of monocytic human leukocyte antigen-dr (mhla-dr), the proportions of dendritic cells (dc) and its subtypes (including myeloid dendritic cell (mdc) and plasmacytoid dendritic cell (pdc)), the different cytokineproducing cd + t helper (th) cells and regular t (treg) cells. plasma crp and several inflammatory mediators levels were measured by elisa. results: compared with healthy controls, there is a significant decrease in the expression of mhla-dr, the frequencies of total circulating dcs and its subsets, and percentage of th cells in patients with psap. however, we found significantly higher frequencies of th cells, higher proportion of treg cells than healthy subjects. of interest, we observed that there was a significant decrease in the positive percentage and mean fluorescence intensity (mfi) of mhla-dr, the proportions of total dcs and pdc, and th cells in patients with pof compared with transient organ failure (tof). besides, there is a significantly higher frequency of th cells in pof than those in tof. area under the receiver-operating characteristic curve analysis showed that disease severity scores had a moderate discriminative power for predicting pof in patients with psap. more importantly, the expression of mhla-dr and the percentage of dcs and pdc had a significantly higher auroc and thus, better predictive ability than disease severity in patients with psap. conclusions: circulating immune profile show multiple aberrations in patients with psap who have developed pof. both the expression of mhla-dr and the percentage of total dc and pdc may be early good biomarkers for predicting risk of pof in patients with psap. introduction: pancreatic fistula (popf) due to anastomosis insufficiency is a common ( - %) complication after pancreaticoduodenectomy and often discovered with delay, causing severe morbidity, icu stay and deaths. microdialysis (md) catheters have been shown to detect inflammation and ischemia in several postoperative conditions and organs. the aim was to investigate if md catheter monitoring could facilitate earlier detection of popf than current standard of care. methods: in a prospective, observational study patients ( to years) were investigated. a md catheter was fixed to the pancreaticojejunal anastomosis. samples for analysis of glucose, lactate, pyruvate and glycerol were acquired hourly during the first hours, then every - hours to discharge. popf was defined according to the international study group of pancreatic fistula update definition. results: patients who developed popf (n= ) had significantly higher glycerol levels (p< . ) in microdialysate than did patients without popf (n= ) during the first h. thereafter, the difference diminished. a glycerol concentration > μmol/l during the first h detected patients who later developed popf with a sensitivity of % and a specificity of %. lactate and lactate to pyruvate ratio were significantly higher (p< . ) and glucose was significantly lower (p< . ) in patients with popf from about h. fig. shows microdialysis measurements in patients with (red lines) and without (blue lines) popf. conclusions: a high level of glycerol in microdialysate is an early (first hours) indicator of popf. glucose, lactate and lactate to pyruvate ratio are indicators of peritonitis caused by the leakage. thus, md monitoring detects popf several days earlier than current methods and may play an important clinical tool in the future. we are currently conducting a rct to explore if md monitoring will improve prognosis in these patients the phenomenon of total impaired of metabolic activity of gut microbiota in critically ill septic patients introduction: during a critical condition, dramatic disturbances occur not only in the change of species diversity, but in gut microbiota metabolism as well, that might lead to nonreversible breakdowns of host homeostasis and death [ ] . metabolic activity of microbes can be assessed by the measurement of the levels of aromatic microbial metabolite (amm) in blood serum, which are associated with the severity and mortality of icu patients. critically ill patients are characterized by the totally different sfs profile than in healthy people, particularly by the absence of phpa; but dominated by p-hphaa and p-hphla [ ] . the purpose of our study is to assess the gut metabolic activity via amm in sepsis. methods: in this study simultaneously serum and fecal samples (sfs) were taken from icu patients: -with sepsis, -chronic critical ill (cci) patients and control - sfs from healthy people. after liquid-liquid extraction from serum and fecal samples, phenylcarboxylic acids (amm) were measured using gc/ms (thermo scientific). results: the sum of the level of most relevant amm in serum samples were higher in patients with sepsis (median - . μm) than in cci patients ( . μm) and healthy people ( . μm). at the same time the opposite pattern was observed in the fecal samples - . , . and . μm, respectively. the ratios of sums amm gut/serum were higher in healthy people than icu patients (fig. ) introduction: the aim of this study is to describe the characteristic of bioelectric impedance vector analysis (biva) and muscular ultrasound during the first week after admission in the icu, and their correlation with indices of metabolic support. biva is a commonly used approach for body composition measurements [ ] . muscular ultrasound represents a valid tool to provide qualitative and quantitative details about muscle disease [ ] . methods: consecutive patients admitted to icu and expected to require mechanical ventilation for at least hours were enrolled in the study. within the first hours of icu admission (t ), patients were evaluated with muscular ultrasonography comprehensive of diaphragm thickness (dth) and rectus femoris cross-sectional area (csa). at the same time, biva and biochemical analysis. all the same measures were repeated at day (t ) and (t ) (figure (table ) . dividing the patients in two groups based on prealbumine changes (t vs t : increase, anabolic vs decrease, catabolic), those in which prealbumine increased had a higher reduction in muscle mass ( figure ). conclusions: this study showed how the pa tends to be reduced in the first week of icu stay. it is correlated with a concomitant introduction: the modified nutrition risk in critically ill (mnutric) has been developed in order to identify critically ill patients who may receive benefit from nutrition support [ ] . several evidences showed the association between the mnutric score and clinical outcomes [ , ] , however there are no data in thai critically ill patients. the purpose of this study was to find the association between mnu-tric score and -day mortality in medical intensive care unit (icu) patients, ramathibodi hospital. methods: we retrospectively reviewed the medical patient records from june to january . a mnutric score of each patient was calculated to evaluate the risk of malnutrition. statistical analysis of the association between mnutric score and -day mortality, length of stay in icu and hospital were performed. results: a total of critically ill patients were included in the study. the -day mortality was . % in patients with high mnutric score ( - ) and . % in patients with low mnutric score ( - ). modified nutric score was significantly correlated with day mortality (r = . , p< . ), length of stay in icu (r = . , p< . ) and length of stay in hospital(r = . , p< . ). in the receiver operating characteristic (roc) curve analysis, the auc of mnutric score and -day mortality was . ( % confidence interval (ci), . - . ) (fig ) . optimal cut-off value of showed sensitivity of . % and specificity of . % in mortality prediction (youden's index, . ). additionally, patients who received adequate nutrition supplement within days was . % for calorie and . % for protein. there was no association between nutrition support and -day mortality. conclusions: in thai medical intensive care population, the mnutric score was associated with -day mortality in critically ill patients. fig. (abstract p ) . within the first hours of icu admission (t ), patients will be evaluated with muscular ultrasonography comprehensive of diaphragm thickness and rectus femoris (medial vastus) cross-sectional area. at the same time, anthropometric measure will be collected (such as body height, ideal body weight, real body weight declared, right arm circumference) as well as biva measure (xc, r, pa, lean body weight and % of extracellular body weight) and biochemical analysis (inclusive albumin, pre-albumin, blood count, lymphocyte count, magnesium, phosphorus, reticulocytes, renal and hepatic function test). the day after, the fluid balance will be calculated as well as the nitrogen balance. all the same measures will be repeated at day (t ) and days (t ) introduction: ultrasonography is an essential imaging modality in critical care to diagnose and guide for therapeutic management of shock, multiple organ failure, etc. enteral tube feed intolerance occurs frequently in hospitalized patients and more so in critically ill patients. in present study, we consider that nursing staff may be able to use bedside ultrasound as an alternative to standard aspiration protocol or radiographic studies to assess gastric volume and nasogastric (ng) tube in patients with enteral feed intolerance. methods: in present prospective, single-center study, we performed ultrasound residual stomach volume and ng tube placement assessments of adult critically ill patients (figure ) compared to standard protocol of stomach volume assessment (routine daily shift -ml syringe aspirations) and ng (nasogastric) tube placement verified by abdominal x ray. we used an abdominal (linear ultrasound transducer) probe ( - mhz). the residual volume was calculated according to formula: gv (ml) = + . x right-lateral csa- . x age). results: hundred simultaneous double (ten critically ill patients) ultrasound measurements sessions were performed by nursing staff of our intensive care (icu) (fig ) . double simultaneous measurements of the ultrasound assessments were compared to standard nurse icu protocol for assessment of residual volume of stomach. the new ultrasound assessment method demonstrated excellent intra-class reliability (icc- . ( . - . , p< . ) and strong correlation with standard residual volume assessment method (icc- . ( . - . , p< . ). ng tube placement was successfully verified by ultrasound measurements in all ten critically ill patients and, thereafter, confirmed by abdominal x-rays. conclusions: preliminary results of our study demonstrated good correlations between both methods of ng tube placement and residual stomach volume: standard icu nurse protocol and ultrasound assessment. evaluating the documentation of nasogastric tube insertion and adherence to safety checking l roberts introduction: enteral feeding into a misplaced nasogastric (ng) tube is recognised by the national patient safety agency as a never event. ng tubes are commonly indicated in level / patients, thus we set out to evaluate current practice in critical care. the aim was to evaluate: documentation of insertion, adherence to safety guidance pertaining to checking safe use, chest x-ray interpretation. methods: this prospective cohort study was based on inpatients in critical care who had insertion of ng tubes over four weeks; there were insertions. data was analysed from patients' medical notes and the hospital's imaging system. results: % of insertions were documented using proformas. . % of proforma documentations included or more details: type of tube, tube length at the nostril, nex measurement, aspirate adequacy, chest x-ray adequacy, whether it was safe to feed. only . % of hand-written documentations included or more details. % of initial aspirates were obtained on insertion, of these, % had an appropriate ph between and . . this led to % of patients having chest x-rays to confirm initial placement of the ng tube. only % of chest x-rays adequately satisfied the four criteria. written documentation in medical notes stating if it was safe to feed was completed in % of cases. conclusions: we found that proformas ensure a higher level of detail and uniformity in the documentation of ng tube insertions. there was a high incidence of chest x-rays performed to confirm correct placement of tubes due to difficulties in obtaining aspirates and failure to follow guidelines. a need for a uniform, ward-specific proforma on ng tube insertion has been identified, as well as a teaching session on chest x-ray interpretation and on techniques to aid obtaining aspirates. we have established critical care's shortcomings in ng tube insertion documentation and tube safety checking. introduction: pressure ulcers(pu) are considered as important types of public health problems, due to high mortality and cost. we aimed to investigate the efficiency of curcumin and fish oil on prevention and treatment of pu using a feasible mice model. methods: mice were randomly divided into control(group ), curcumin(group ), fish oil(group ), curcumin and fish oil(group ) groups. mm skin bridge between two gauss magnets was formed on the back of mice, followed by ischemia reperfusion cycles as hours of rest after hours of magnet placement [ ] . a single dose of curcumin and fish oil was injected intraperitoneally. tissue samples had taken th day of first compression, rates of pu, inflammation, reepithelisation, neovascularisation and granulation were examined histopathologically. the data analyzed by pearson chi-square test. results: third degree pu were observed in all groups.there was no significant difference between groups in terms of inflammation.the formation of reepithelisation showed a significant difference between groups.partial reepithelisation ratios in group and group was elevated.there was significant difference between groups in terms of neovascularisation, the highest rate as % was observed in group .formation of granulation was observed at maximum rate as . % at group . conclusions: depending on positive results of curcumin, fish oil, cur-cumin+fish oil on wound healing it may be advised to use them in treatment of acute pu.after similar rate of pu with control group we consider that it should be beneficial to evaluate the effect of these therapies with more studies by changing the mode of administration, time of initiation and duration of therapy. introduction: inflammation is a key driver of malnutrition during acute illness and has different metabolic effects including insulin resistance and reduction of appetite. whether inflammation influences the response to nutritional therapy in patients with disease-related malnutrition remains undefined. we examined whether the effect of nutritional support on the risk of mortality differs based on the inflammatory status of patients. methods: this is a secondary analysis of a multicentre trial in eight swiss hospitals, where patients with a nutritional risk score (nrs) of ≥ upon hospital admission were randomly assigned to receive protocol-guided individualized nutritional support according to nutrition guidelines (intervention group) or a control group. the inflammatory status was defined based on admission crp levels as low inflammation (cpr < mg/dl), moderate inflammation (crp - mg/dl) and high inflammation (crp > mg/dl). results: we included a total of , patients of which . %, . % and . % had low, moderate and high inflammation levels on admission. while overall there was a significant reduction in day mortality associated with nutritional support (adjusted or in the overall cohort . , %ci . - . ), the subgroup of patients with high inflammation did not show reduced mortality (adjusted or . , %ci . - . , p for interaction = . ). there was no difference in other secondary endpoints when stratified based on inflammation. nutritional support did not affect crp levels over time (kinetics). conclusions: this secondary analysis of a multicentre randomized trial provides evidence, that the inflammatory status of patients influences their response to nutritional support. these findings may help to better individualize nutritional therapy based on patients initial presentation. introduction: low plasma glutamine levels have been associated with unfavourable outcomes in critically ill patients. this study aimed to measure plasma glutamine levels in critically ill patients and to correlate glutamine levels with biomarkers and severity of illness. methods: we enrolled critically ill patients admitted to three icus in south africa, excluding those receiving glutamine supplementation prior to admission. we collected clinical, biochemical and dietary data. plasma glutamine levels were determined within hours of admission, using liquid chromatography mass spectrometry and categorized as low (< μmol/l), normal ( - μmol/l) and high (> μmol/l). results: of the patients (average age . ± . years, % male), % were mechanically ventilated, with a mean apache ii score of . ± . and a mean sofa score of . ± . . plasma glutamine levels were low in . % (median plasma glutamine of . μmol/l). baseline plasma glutamine correlated inversely with crp (r=- . , p< . ) and serum urea (r=- . , p< . ), and positively with serum bilirubin (r= . , p< . ) and serum alt (r= . , p= . ). significantly more patients with low admission glutamine levels required mechanical ventilation (chi = . , p< . ) and had higher apache scores (p= . ), higher sofa scores (p= . ), higher crp values (p< . ), higher serum urea (p= . ), higher serum creatinine (p= . ), lower serum albumin (p< . ) and lower bilirubin levels (p= . ). using multiple logistic regression analysis, apache score (odds ratio, [or] . , p= . ), sofa score (or . , p= . ) and crp (or . , p< . ) were significant predictors of low plasma glutamine levels. roc curve analysis revealed a crp threshold value of . mg/l to be indicative of low plasma glutamine levels (auc . , p< . ). conclusions: . % of critically ill patients had low plasma glutamine levels on admission to icu. this was associated with increased disease severity and higher crp. introduction: the east of england deanery operational delivery network in the united kingdom came together as a group of intensive care units to comply an evidence-based care bundle. one of the branches of this care bundle is on parenteral nutrition and states: 'parenteral nutrition should not be given to adequately nourished, critically ill patients in the first seven days of an icu stay.' this is based on evidence [ ] [ ] [ ] that showed that 'in patients who are adequately nourished prior to icu admission, parental nutrition initiated within the first seven days has been associated with harm, or at best no benefit, in terms of survival and length of stay in icu.´the objective of this second cycle was to assess whether or not we are adhering to the guidelines, last year we were failing to hit targets and after some action i reassessed how we performed in the year compared to . methods: a retrospective audit of the whole year of for all patients admitted to icu who had parenteral nutrition started at any point during their stay. results: there is a significant improvement in the percentage of patients who are being started incorrectly on tpn before days ( % compared to %) (fig , ) . i also found a total reduction in the number of patients prescribed tpn, a reduction in the number of bags being used and a reduction in length of hospital stays. conclusions: as we have recently switched over to an electronic icu programme for all documentation and prescriptions, as part of our plan and act in the pdsa cycle we are organising for several things to be put in place on the new system on prescription: pharmacy authorisation, links to guidelines and alert/justification boxes. i will do a further cycle in another year. jg and mpc contributed equally. introduction: recent rcts revealed clinical benefit of early macronutrient restriction in critical illness, which may be explained by enhanced autophagy, an evolutionary conserved process for intracellular damage elimination [ ] . however, in the absence of specific and safe autophagy-activating drugs, enhancing autophagy through prolonged starvation may produce harmful side effects. a fasting-mimicking diet (fmd) may activate autophagy while avoiding harm of prolonged starvation, which also improved biomarkers of age-related diseases in an experimental study [ ] . we evaluated if short-term interruption of continuous feeding can induce a metabolic fasting response in prolonged critically ill patients. methods: in a randomized cross-over design, prolonged critically ill patients receiving artificial feeding were randomized to be fasted for hours, followed by hours full enteral and/or parenteral feeding, or vice versa. patients were included at day in icu and blood glucose was maintained in the normal range. at the start and after and hours, we quantified total bilirubin, urea, insulin-like growth factor-i (igf-i) and beta-hydroxybutyrate (boh) in arterial blood. insulin requirements were extracted from patient files. changes over time were analyzed by repeated-measures anova after square root transformation. results: as compared to hours of full feeding, hours of fasting decreased bilirubin (- . ± . mg/dl; p= . ) and igf-i (- . ± . ng/ml; p< . ), and increased boh (+ . ± . mmol/l; p< . ), without affecting urea concentrations (fig ) . fasting reduced insulin requirements (- . ± . iu/hour; p< . ). conclusions: short-term fasting induces a metabolic fasting response in prolonged critically ill patients, which provides perspectives for the design of a fmd, aimed at activating autophagy and ultimately at improving outcome of critically ill patients. introduction: recent evidence has led to changed feeding guidelines for critically ill patients, with a shift towards lower feeding targets during the acute phase [ ] . when micronutrients are not provided separately, prolonged hypocaloric feeding could induce micronutrient deficiencies and increase risk of refeeding syndrome once full feeding is restarted, which are both potentially lethal complications [ ] . since there is limited evidence how to optimize micronutrient provision in order to avoid deficiencies, we hypothesized that there is a great variation in current practice. methods: within the men section of the european society of intensive care medicine (esicm), we designed a questionnaire to gain insight in the current practice of micronutrient administration. in email blasts, invitations were sent to all esicm members, with currently more than respondents. the survey will be closed at december , . results: first, we will describe demographic characteristics of the respondents, including geographical location, icu and hospital type, and function. second, we will describe some aspects of the current practice of micronutrient administration. we will identify the proportion of respondents having a protocol, on which evidence such protocol is based and whether it takes into account the stability and daylight sensitivity of micronutrients. next, bearing refeeding syndrome in mind, we will identify whether there are respondents who never measure and/or separately administer micronutrients and phosphate. finally, we will make a top of the most measured and most supplemented micronutrients. conclusions: this survey will deliver more insight in the current practice of micronutrient provision across different types of icus and may identify areas for future research. furthermore, we will evaluate whether there is need to increase awareness for refeeding syndrome. introduction: large gastric residual volumes (grvs) have been used as surrogate markers of delayed gastric motility to define enteral feeding intolerance (efi). recent studies have challenged the definition of efi. study objectives: ) investigate the potential relationship between grvs and clinically outcomes, ) develop an algorithm for early identification of patients at increased risk of mortality due to efi. methods: a retrospective study of inpatient encounters from electronic health record charts within the dascena clinical database. , patients were included in the study; patients had efi. eight vital signs (diastolic/systolic bp, heart rate, temperature, respiratory rate, grv, glasgow coma scale, and feeding rate) and their trends were input to the classifier. machine learning classifiers were created using the xgboost gradient boosted tree method with -fold cross validation. results: rate of change in grv (Δ grv) was measured over a -day period, beginning at the time of efi onset (figure a) . figure b shows a high likelihood of mortality for patients with none or modest grv reduction. patients with an increase in grv over the five-day period after efi onset had the highest mortality likelihood. a stratification algorithm was developed to identify efi patients who died inhospital despite grv reduction at , , and hours in advance of efi onset. area under the receiver operating characteristic (auroc) curves demonstrated high sensitivity and specificity of algorithm predictions of in-hospital death up to hours in advance of efi onset (table ) . conclusions: the analysis suggests an association between grv and mortality, especially in patients with persistent grv increase over the -day period after efi onset and the potential of algorithmic models to predict efi development. prospective validation of these fig. (abstract p ) . changes in metabolic markers of fasting over time for both randomization groups algorithms may assist in clinical trial design to develop treatments for patients at highest risk of experiencing serious outcomes due to efi. a quality improvement project to improve the daily calorific target delivery via the enteral route in critically ill patients in a mixed surgical and medical intensive care unit (icu) b johnston, d long, r wenstone royal liverpool and broadgreen university hospital trust, critical care, liverpool, united kingdom critical care , (suppl ):p introduction: 'iatrogenic underfeeding' is widespread with the calo-ries study reporting only %- % of prescribed daily kcal was actually delivered to patients [ ] . in the present project, quality improvement methodology was utilised with the aim of delivering greater calories by implementing -hour volume-based feeding and allowing increased feeding rates for, 'catch up' of missed daily feed volume. methods: baseline data assessing the percentage of daily kcal delivered to ventilated patients was collected in september . data was presented and new intervention guidelines agreed based upon the pepup protocol [ ] . nurse champions were identified and were responsible for cascade training of the pepup protocol. educational tools to help determine daily calorific requirement and volume of feed required were provided. repeat data was collected at months (cycle ) after pepup implementation. results: ten patients were included in cycle . during cycle the percentage of kcal achieved via enteral feeding was %. following intervention this increased to % (p< . ) during cycle . this increased further to . % of daily kcal when calories obtained from propofol were included. conclusions: a -hour volume-based feeding regimen is a simple and cost-effective method of improving enteral feeding targets. through the use of quality improvement methodology, we demonstrated that this approach is achievable. the success of this project has led to the adoption of the protocol in other icu units in a regional critical care network. effect of non-nutritional calories on the calory/protein ratio in icu patients s jakob, j takala university hospital bern, dept of intensive care medicine, bern, switzerland critical care , (suppl ):p introduction: nutritional diets are composed to match the needs of critically ill patients. while effective calory needs can be measured or calculated, the needs of proteins are more controversial. we aimed to calculate non-nutritional calories and assess how they influence the ratio of calories to protein delivered to the patients. methods: in this retrospective analysis, nutritional and nonnutritional calories and protein delivery were calculated in consecutive icu patients receiving enteral nutrition in . introduction: marked protein catabolism is common in neurocritical patients. optimal nutritional monitoring and protein nutritional adequacy could be associated with outcome in neurointensive care unit (ncu) patients. we aimed to evaluate the impact of monitoring and optimal support of protein using nitrogen balance on outcome in neurocritical patients. methods: a consecutive patients who were admitted to ncu were included between july and february . nitrogen balance was calculated using excreted urine urea nitrogen during icu admission. follow-up nitrogen balance monitoring was performed in patients. we divided patients into two groups based on the results of nitrogen balance (positive balance and negative balance). moreover, we evaluated improvement of nitrogen balance in patients. we assessed the outcome as length of stay in hospital, length of stay in ncu, and in-hospital mortality. we compared the clinical characteristics and outcome according to nitrogen balance. results: among the included patients (age, . ; and male. . %), ( . %) patients had negative nitrogen balance. the negative balance group was more likely to have lower glasgow coma scale (gcs), longer length of stay in hospital, and longer length of stay in ncu. in patients with follow-up nitrogen balance monitoring, improvement of nitrogen balance group had lower in-hospital mortality ( . % vs. . %, p = . ), and received adequate protein intake ( . g/kg/day vs. . g/kg/day, p = . ) compared to no change group (table ) . there was no significant difference in baseline nitrogen balance, baseline body mass index, and gcs between two groups. conclusions: this study demonstrated that critical illness patients in ncu are underfeeding using nitrogen balance, however, adequate provision of protein was associated improvement of nitrogen balance and outcome. this suggests that adequate nutrition monitoring and support could be an important factor for prognosis in neurocritical patients. increased protein delivery within a hypocaloric protocol may be associated with lower -day mortality in critically ill patients introduction: to test the hypothesis, using real world evidence that increasing protein delivery and decreasing carbohydrates (cho) may improve clinical outcomes. methods: retrospective analysis of existing electronic medical records (emr) of patients admitted to the intensive care units (icu) at the geisinger health system. logistic regression analysis was used to determine correlation between protein delivered (which was proportional to the concentration of protein in the formula utilized) and clinical outcomes. results: medical encounters for a total number of , icu days were collected and analyzed. average age was . years ( . % male) and . % were obese and overweight. primary diagnoses included sepsis or septic shock, acute and/or chronic respiratory failure (or illness), cardiovascular diseases, stroke and cerebrovascular diseases among others. median hospital los was . days, . days in the icu, median days of invasive mechanical ventilation of . -day readmission rate among patients discharged alive was . %. patients in the high protein group received lower amounts of chos (data not shown). unadjusted -day post-discharge mortality was inversely proportional to the amount of protein delivered (table ) . conclusions: a significant improvement in mortality is observed with increased protein delivery while decreasing carbohydrate loads. prospective randomized trials are warranted to establish causality. introduction: acute kidney injury (aki) is associated with high mortality. the risk increases with severity of aki. our aim was to identify risk factors for development and subsequent progression of aki in critically ill patients. methods: we analysed patients without end-stage renal disease who were admitted to the icu in a tertiary care centre between january to december and did not have aki on admission. we identified risk factors for development and non-recovery of aki as defined by the kdigo criteria. results: the incidence of new aki in days was % (aki i %, aki ii %, aki iii %). multivariate analysis revealed bmi, sofa score, chronic kidney disease (ckd) and cumulative fluid balance as independent risk factors for development of aki. among patients who developed aki in icu, % had full renal recovery, % partial recovery and % had no recovery of renal function by day . aki patients without renal recovery in days had significantly higher hospital mortality ( %) compared to the other groups. independent risk factors for non-recovery of renal function were ckd, mechanical ventilation, diuretic use and extreme fluid balance before and after first day of aki. (table ) the association between cumulative fluid balance before aki and hours after aki with risk of aki non-recovery are shown in figure and . conclusions: aki is common and mortality is highest in those who do not recover renal function. cumulative fluid accumulation impacts chances of aki development and progression. (table ). all were in r . / ( %) of those with an admission ck> had aki or . all ( %) patients who required crrt for aki associated with rm were at risk for aki regardless of initial ck: vascular surgery ( / ), multi-organ dysfunction ( / ), and/or pre-existing renal disease ( / ). conclusions: raised ck is common in icu but its cause is multi factorial thus an isolated measure > does not require immediate high output treatment for rm aki. aki is more common in patients who have more than ck> on sequential days or those whose first ck was > as rm may be contributing. a single ck> in patients with a clear reason to develop rm should also start treatment. surgical outcomes of end-stage kidney disease patients who underwent major surgery p petchmak , y wongmahisorn , k trongtrakul introduction: acute kidney injury (aki) occurs in more than % of successfully resuscitated out-of-hospital cardiac arrest patients treated with targeted temperature management (ttm) [ ] . the effect of the duration of cooling on aki has not been well studied. in this post-hoc analysis of the tth randomized controlled trial that compared vs -hours of ttm ( °c) after cardiac arrest [ ] , we studied the impact of ttm length on the development of aki. fig. . duration of ttm had a significant impact on the development of creatinine values during the first days in the icu, p< . . this was primarily driven by an increase in creatinine during rewarming on day for the hour and day for the -hour group (fig ) . conclusions: in a trial of vs hours of ttm after out-of-hospital cardiac arrest, the length of ttm did not affect the incidence of aki. fig. (abstract p ) . creatinine over time patients [ ] , but there are no published data on longer-term renal outcomes in adult patients. the purpose of this study was to assess longer-term trends in serum creatinine in this cohort. methods: a retrospective study was conducted of all patients admitted to an adult regional referral centre for ecmo at a uk university hospital between and . those who survived for > months were included. demographics, baseline serum creatinine, presence of aki during icu admission, and serum creatinine at hospital discharge were determined. serum creatinine and dependence on renal replacement therapy (rrt) were assessed at and months post ecmo. results: patients had a complete (or near-complete) data-set available. the mean age was . years, % of whom were male. / had aki during their critical care admission. none were dependent on rrt at or months post ecmo. most patients had lower serum creatinine results at hospital discharge compared to their pre-hospitalisation baseline, but creatinine concentrations at and months post ecmo tended to be higher than at hospital discharge ( figure ) . conclusions: in this cohort of ecmo patients who were discharged from hospital alive, serum creatinine tended to be lower at hospital discharge compared to baseline and rose again in the following months. decreased creatinine production due to deconditioning and muscle wasting may offer a biological rationale for the lower creatinine results at hospital discharge [ ] . therefore, caution should be exercised in the use of serum creatinine at hospital discharge to assess renal dysfunction -further research is warranted. introduction: aki complicates more than half of icu admissions [ , ] and is associated with development of chronic kidney disease (ckd), need for renal replacement therapy (rrt) and increased mortality [ ] . we prospectively evaluated all icu admissions during a one-year period in order to determine incidence, etiology and timing of aki as well relevant clinical outcomes. methods: prospective observational study of all patients admitted from jan to dec to a multidisciplinary icu in greece. patients with end-stage renal disease and anticipated icu stay less than hrs were excluded. aki diagnosis and classification was based on kdigo criteria [ ] . lowest creatinine level within months before admission or first creatinine after icu admission served as reference. (fig ) . conclusions: although aki alert does not include urine output criterion or aki risk factors, it remains a helpful tool to point out patients with aki. education and diagnostic algorithms are still needed to early diagnose and treat aki patients. influence of severity of illness on urinary neutrophil gelatinaseassociated lipocalin in critically ill patients: a prospective observational study c mitaka, c ishibashi, i kawagoe, d satoh, e inada untendo university, anesthesiology and pain medicine, tokyo, japan critical care , (suppl ):p introduction: neutrophil gelatinase-associated lipocalin (ngal) is a diagnostic marker for acute kidney injury (aki). ngal expression is highly induced not only in kidney injury, but also in epithelial inflammation of intestine, bacterial infection, and cancer. however, the relationship between ungal and severity of critically ill patients has not been well understood. the purpose of this study was to elucidate whether ungal is associated with severity of illness and organ failure in critically ill patients. methods: we prospectively enrolled patients with sepsis (n= ) and patients who underwent esophagectomy with gastric reconstruction for esophageal cancer (n= ). sepsis was defined according to sepsis- . ungal levels were measured on icu day , , , and . ungal levels and aki rate in patients with sepsis were compared with those in patients who underwent esophagectomy. aki was defined according to kdigo. acute physiology and chronic health evaluation (apache) ii score and sequential organ failure assessment (sofa) score were calculated. results: median ungal level ( ng/mg creatinine) was significantly higher in patients with sepsis than that ( ng/mg creatinine) in patients who underwent esophagectomy on day . median apache ii score and median sofa score in patients with sepsis were significantly higher than those in patients who underwent esophagectomy. four patients with sepsis developed aki, and out of them underwent continuous renal replacement therapy, whereas no patients who underwent esophagectomy developed aki. ungal levels were positively correlated with apache ii score and sofa score in patients with sepsis. ungal levels were remarkably elevated (> ng/mg creatinine) in urinary tract infection (n= ), loops enteritis (n= ), and obstructive jaundice due to cholangiocarcinoma (n= ). conclusions: these findings suggest that ungal level is associated with severity of illness and organ failure in patients with sepsis. ungal levels might be influenced by severity of illness and inflammation. to assess the quality of the course us renal images had to be evaluated in "post-renal obstruction" (p-ro) or "no p-ro". the rate of correctness (roc farius ) was determined. in we, once again, contacted the students to attend a web-based online "follow-up". this online survey was created with "google formular". new and unknown us images were presented and rated in "p-ro" or "no p-ro" (roc fup introduction: septic-induced kidney injury worsen the patient's prognosis [ ] . renal resistance index (rri) is correlated with an increased mortality in septic patients [ ] . the aim of this study was to describe the evolution of rri in a rat sepsis model. methods: the local ethics committee approved the study (apa-fis# - ). sepsis was induced in -month-old male rats by caecal ligation and puncture (clp) [ ] . the rri was assessed before and h after clp by pulse doppler on the left renal artery (rri=(peak systolic velocityend diastolic peak)/ peak systolic values expressed as % per column. abbreviations in alphabetical order: aki acute kidney injury; akin acute kidney injury network definition; ckd chronic kidney disease. there were statistical differences between subgroups with and without aki for the subgroups of patients with previous ckd (p = . *), sepsis at admission (p = . **), hypotension (p= . ***) fig. (abstract p b) . target comparing accuracy and precision of aki alert and actual aki diagnoses velocity) (fig ) . rri were compared by a paired wilcoxon test (r software v. . . ). a p value < . was considered significant. results: rats were included. hours after sepsis induction, all rats were in septic shock with cardiac dysfunction. the rri increased after sepsis induction compared to baseline ( . ± . vs . ± . , p< . ) and mean renal artery velocity decreased ( . ± . vs . ± . , p< . ) (fig ) . systolic and diastolic peaks velocity of the renal artery were unchanged. conclusions: sepsis induced changes in rri and mean velocity on the left renal artery whereas no changes in systolic or diastolic velocities were seen. these results are consistent with available clinical datas. the rri could be an additional tool to assess renal failure in septic rats. further studies are needed to confirm the validity of this marker during sepsis. kidney failure is one of the most common organ dysfunction during sepsis. the rri could be an additional tool in small animals to assess the effects of potential therapeutic targets on renal function induced by sepsis. (fig ) . the egfr improved more with the heparin group ( % vs %; p= . ) (fig ) . interruptions of the filter circuit were as expected less with the citrate group ( mins vs mins; p= . ). finally, inotropic requirements increased following therapy interruptions, more so with patients receiving citrate ( . % vs . %; p= . ). conclusions: our analysis suggests that using citrate anticoagulation for rrt results in a monitoring cost saving of approximately £ per hours, alongside the other conferred savings previously reported. furthermore, results demonstrate the efficacies of both systems are similar in the initial hours, although there is a suggestion that heparin systems improves renal parameters more quickly. finally, interruptions and 'filter downtime' caused an increase in the patient's inotropic requirements, however results suggestive that this is greater in the citrate group. mmol/l respectively. demographic characteristics of the study group and the main parameters of the procedure were presented in fig . conclusions: regional citrate is a safe and effective anticoagulation method for crrt in children, when it is applied following a protocol. it significantly prolongs circuit survival time and thereby should increase crrt efficiency. we did not find any serious adverse effects of regional citrate anticoagulation. - ) , deceased at year n= ( %). the mdrd trend is more indicative than creatinine of decline of renal function in the post operative period (fig ) . crrt was used in . % ( pts) and was associated to a greater los and mortality (fig ) . preoperative bilirubin, bun and creatinine are among the greatest risk factors for its use ( table . at year follow up n= pts ( . %) were on hemodialysis. conclusions: aki requiring crrt in after lt is associated with higher mortality and los. identify patients at risk and adopt preventive strategies in the perioperative period is mandatory. introduction: we developed a new co removal system, which has a high efficiency of co removal at a low blood flow. to evaluate this system, we conducted in vivo studies using experimental swine model. methods: six anesthetized and mechanically ventilated healthy swine were connected to the new system which is comprised of acid infusion, membrane lung, continuous hemodiafiltration and alkaline infusion. in vivo experiments consist of four protocols of one hour; baseline= hemodiafiltration only (no o gas flow of membrane lung); membrane lung = "baseline" plus o gas flow of membrane lung; "acid infusion" = "membrane lung" plus continuous acid infusion; "final protocol" = "acid infusion" plus continuous alkaline infusion. we provided an interval period of one hour between each protocol. we changed the respiratory rate of the mechanical ventilation to maintain pco at - mmhg during the experiment. results: the amount of co eliminated by the membrane lung (vco ml) significantly increased by . times in the acid infusion protocol and our final protocol compared to the conventional membrane lung protocol, while there was statistically no significant difference observed in the levels of ph, hco -, and base excess between each study protocol. minute ventilation in the "final protocol" significantly decreased by . times compared with the hemodiafiltration only protocol (p < . ), the membrane lung (p= . ) and acid infusion protocol (p= . ). we developed a novel ecco r system which efficiently removed co and is easy-to-setup to permit clinical application. this new system significantly reduced minute ventilation, while maintaining acid-base balance within the normal range. further studies are needed for the clinical application of this easy setup system comprising of the materials typically used in a clinical setting. , and psychomotor agitation ( %) while the most common symptoms of hypertensive emergency were chest pain ( . %), dyspnea ( . %) and neurological deficit ( %). clinical manifestations of hypertensive emergency were cerebral infarction ( . %), acute pulmonary edema ( . %), hypertensive encephalopathy ( . %), acute coronary syndromes ( . %), cerebral hemorrhage ( ,. %), congestive heart failure ( %), aortic dissection ( . %), preeclampsia and eclampsia ( . %). conclusions: hypertensive urgencies were significantly more common than emergencies ( . % vs. . %, p< . ). there was no statistically significant difference in the number of patients with hypertensive urgency and emergency in relation to age, gender, duration of hypertension, except for the - age group, where urgency was statistically significantly higher (p= . ). introduction: emergency department (ed) crowding is a major public health concern. it delays treatment and possible icu admission, which can negatively affect patient outcomes. the aim of this study was to investigate whether ed to icu time (ed-icu time) is associated with icu and hospital mortality. methods: we conducted an observational cohort study using data from the dutch nice registry. adult patients admitted to the icu directly from the ed in academic centers, between and , were eligible for inclusion. for these patients nice data were retrospectively extended with ed admission date and time. ed-icu time was divided in quintiles. the data were analyzed using a logistic regression model. we estimated crude and adjusted (for disease severity; apache iv probability) odds ratios of mortality for ed-icu time. in addition, we assessed whether the apache iv probability (divided into quartiles) modified the effect of ed-icu time on mortality. results: a total of , patients were included. baseline characteristics are shown in table . the median ed-icu time was . [iqr . - . ] hours. icu and hospital mortality were . and . %, respectively. the crude data showed that an increased ed-icu time was associated with a decreased icu and hospital mortality (both p< . , figure a ). however, after adjustment for disease severity, an increased ed-icu time was independently associated with increased hospital mortality (p< . , figure b ). figure shows that only in the sickest patients (apache iv probability > . %), the association between increased ed-icu time and hospital mortality was significant (p= . , figure d ). we found similar results with respect to icu mortality. conclusions: this study shows that a prolonged ed-icu time is associated with increased icu and hospital mortality in patients with higher apache iv probabilities. strategies aiming at rapid identification and transfer of the sickest patients to the icu might reduce inhospital mortality. reliability and validity of the salomon algorithm: -year experience of nurse telephone triage for out-of-hours primary care calls e brasseur, a gilbert, a ghuysen, v d´orio chu liege, emergency departement, liège, belgium critical care , (suppl ):p introduction: due to the persistent primary care physicians (pcp) shortage and their substantial increased workload, the organization of pcp calls during out-of-hours periods has been under debate. the salomon (système algorithmique liégeois d'orientation pour la médecine omnipraticienne nocturne) algorithm is an original nursing telephone triage tool allowing to dispatch patients to the best level of care according to their conditions [ ] . we aimed to test its reliability and validity under real life conditions. methods: this was a -year retrospective study. out-of-hours pc calls were triaged into categories according to the level of care needed: emergency medical services (amu), emergency department visit (maph), urgent pcp visit (upcp), delayed pcp visit (dpcp). data recorded included patients' triage category, resources and potential redirections. more precisely, patients included into the upcp + dpcp cohort were classified under-triaged if they had to be redirected to an emergency department. patients from the amu+maph cohort were considered over-triaged if they did not spend at least resources, emergency specific treatment or any hospitalization. results: calls were actually triaged using the salomon tool, of which . % were classified as amu, . % as maph, . % as upcp and . % as dpcp (fig ) . as concerns the amu+maph cohort, the triage was appropriate in . % of the calls, with an over-triage rate of . %. as concerns the upcp + dpcp cohort, . % of the calls were accurately triaged and only . % were under-triaged. sal-omon sensitivity reached . % and its specificity . %. these results indicate that salomon algorithm is a reliable and valid nurse telephone triage tool that has the potential to improve the organization of pcp out-of-hours work. introduction: inappropriate visits to the emergency department (ed), such as patients manageable by a primary care physician (pcp), have been reported to play some role in the ed crowding [ ] . indeed, non-urgent patients directly managed by pcps could reduce ed workload [ ] . triage and diversion to alternative care facilities, eventually co-located within the ed, could offer a solution [ ] provided fig. (abstract p ) . distribution of different calls, their triage using the salomon algorithm and the inappropriate triages (over and undertriages) based on the preselected criteria the availability of a reliable triage tool for their early identification. we created a new triage algorithm, persee (protocoles d'evaluation pour la réorientation vers un service efficient extrahospitalier) and tested its feasibility, performance and safety. methods: after initial evaluation with a -level ed triage scale [ ] , ambulatory self-referred patients classified as level or below benefited from a simulated triage with persee identifying categories of patients: ed ambulatory patients and primary care (pc) treatable patients. we collected patients data and resources. patients requiring less than resources, no specific emergency treatment and no hospitalization were considered as manageable in a pc facility. results: patients were included in the study of whom . % were self-referred (fig ) . among those self-referrals, . % were triaged as level or below. . % patients were triaged as ambulatory patients of whom % were as pc treatable. we noted a redirection rate of % of the global visits or % of the self-referrals, an error rate of %, a sensitivity of . % and specificity of . %. conclusions: using advanced ed triage algorithm in addition to classical ed triage might offer interesting perspectives to safely divert self-referrals to pc facilities and, potentially, reduce ed workload. introduction: generally, prehospital medical provider should minimize staying prehospital scene to reach the patient to definitive care as soon as possible in prehospital medical activity. in addition, some textbook and report saids that medical provider minimize the number of procedure or limit minimum requirement procedure because unnecessary procedure may extend the staying time in prehospital scene. however, there are few studies evaluating this hypothesis and that this "extension is significant or not. therefore, we perform this study. methods: we evaluated the operated air ambulance(doctor-heli) case from st april to st march , in gifu university hospital using our mission record. we evaluated about time from landing to ready for taking off(activity time), operation doctor, mission category (i.e. trauma), number of procedure in the each activity and work load. we only focused on prehospital care and exclude transportation from hospital to hospital . in addition, we exclude the case which are not suitable for analysis. results: cases were operated in these period. cases were suitable for analysis. average activity time in prehospital scene was . ± . . there was weak correlation between the number of procedure and activity time. (r= . ) the length of the activity time did not depend on mission category. if the doctor perform and over procedures, staying time was minutes longer, this was significantly longer than that of under and under procedures. conclusions: we confirmed that we have to minimize the number of procedure or limit minimum requirement procedure in prehospital scene. and our result suggest we may have to limit appropriate number of procedures. introduction: organ failure is a critical condition, but the prevalence is largely unknown among unselected emergency department (ed) patients. knowledge of demographics and risk factors could improve identification, quality of treatment, and thereby improve the prognosis. the aim was to describe prevalence and all-cause mortality of organ failure upon arrival to the ed. methods: this was a cohort-study at the ed at odense university hospital, denmark, from april , to march , . we included all adult patients, except minor trauma. organ failure was defined as a modified sofa-score > within six possible organ systems: cerebral, circulatory, renal, respiratory, hepatic, and coagulation. the first recorded vital, and laboratory values were extracted from the electronic patient files. primary outcome was prevalence of organ failure; secondary outcomes were - -day and - -day mortality. results: of , contacts . % were female and median age (iqr - ) years. the prevalence of new organ failure was . %, individual organ failures; respiratory . %, circulatory . %, cerebral . %, renal . %, hepatic . %, and coagulation . %. the - -day and - -day all-cause mortality was . % ( % ci: . - . ) and . % ( % ci: . - . ), respectively, if the patient had new organ failures at first contact in the observation period, compared to . % ( % ci: . - . ) and . % ( % ci: . - . ) for patients without. seven-day mortality ranged from hepatic failure, . % ( % ci: . - . ) to cerebral failure, . % ( % ci: . - . ), and the - -day mortality from cerebral failure, . % ( % ci: . - . to renal failure, . % ( % ci: . - . ). conclusions: new organ failure is frequent and serious, with a prevalence of . % and a one-year mortality of % with wide variation according to type of organ failure. results: we proceeded to a descriptive study that showed that % of patients were male and % of them were female with a sex ratio of . .the average age of patients was years old and ranged between and years old.we found that patients of our population had medical background, dominated by diabetes in cases, high blood pressure in cases and asthma in cases.the results also showed that . % of patients had a history of abdominal surgery while % of them had history of other types of surgery.the patients were oriented according to their severity level as following: % care unit of emergency department, . % close monitoring room .the vaspi score was ranged between and with an average of ± . it was higher than in . % of cases.the results of physical examination found an isolated pain in , % of cases, a reactionnal pain syndrom in % of cases, a peritoneal syndrome in % of cases and an occlusive syndrome in % of cases.the final diagnosis was mostly represented by the following causes: . % of gastroenteritis . % of constipation and % of ulcer disease.the final orientation of patients according to the diagnosis led to hospitalization in % of cases and to outpatient clinic in % of cases while % of them did not need any more care. conclusions: appropriate diagnostic evaluation and decision for or against hospitalization is a challenge in the patient who comes to the emergency department with acute abdominal pain it need an adequate evaluation and management. introduction: we assessed patients' impressions of a selfadministrated automated history-taking device (tablet) to gather information concerning emergency department (ed) patients prior to physicians' contact. the quality of communication was compared with the traditional history-taking. methods: the algorithm content was developed by two emergency physicians and two emergency nurses through an iterative process. item-content validity index (i-cvi) was measured by five experts rating the relevance of each item (from : not relevant to : highly relevant) [ ] . next, quality control was realized by research team. to assess the feasibility, we used a computerized randomization. low acuity, ambulatory adult patients presenting to the ed were assigned either to a control group (cg, n= ) beneficiating form a traditional history-taking process or to the experimental group (eg, n= ) assigned to use the tablet with further history-taking by the ed physician. communication was analyzed by the health communication assessment tool [ ] and satisfaction assessed by questionnaires. results: after two rounds, validity was excellent for each item (i-cvi > . ). the universal agreement method was of . . refusals (n= ) to participate were analyzed: they fear using an electronic device or the experimentation. content satisfaction revealed that % of patients understood the questions. % of patients indicated that the device was easy to hold and use. medical communication was not affected by the device (p= . ). we noticed that, among the subsections, physicians significantly introduced themselves better in the eg (p= . ). conclusions: in this feasibility study, patients were highly satisfied. the use of a self-administrated automated history-taking device does not generate miscommunications and allow physicians better introduce themselves. . a positive point we have established is the possibility for the detorsion of a twisted retention ovarian cyst after its transvaginal aspiration. we used this method only in cases when the onset of torsion did not exceed hours. . % of all emergency conditions associated with retention cysts were recurred by conservative therapy, and . % of patients with the retention cysts rupture were successfully treated in this way. conservative management is possible in the case of a small loss of blood (up to . - . ml), hemodynamic stability and the absence of signs of continuing bleeding. the detorsion and resection of the cyst when torsion is not more than °and even longer than hours, in most cases did not reveal necrosis in the appendages. conclusions: improvement of organs of preservation and reproduction in women. criteria for admission to an intensive care unit of a tertiary hospital: analysis of the decisions of the outreach intensivist and day in-hospital mortality introduction: the aim of this study was the analysis of icu admission criteria and evaluation of in-hospital mortality of patients assessed by our critical care outreach team. criteria for admission to the icu should be defined to identify the patients most likely to benefit from icu admission. this triage process is complex, associated with several factors, including clinical characteristics of the patients, but also subjective factors because it depends on the judgment of the intensivist who decides whether to admit or not the patient and is obviously conditioned to the structure and size of the icu. methods: the outreach intensivist records the patient observation in a form with questions (reversibility of acute illness, objective of admission in icu, comorbidities, functional reserve and intuitive prognosis of the doctor). analysis of months (january through june , ) of admission decisions in icu, mean delay, icu mortality, and day in-hospital mortality ( hm). results: the intervention of the intensivist in "outreach" was requested on occasions. the main places of observation were the emergency room ( . %) and the wards ( . %). the hm increased with the degree of comorbidity decompensation. functional reserve also influenced hm, reaching . % in partially dependent patients and . % in totally dependent patients. there was agreement between the mortality and the physician´s intuitive prognosis in % of the cases. conclusions: a larger sample is needed to draw sustainable conclusions, however, the evaluation algorithm correlated well with hospital mortality. decompensated comorbidities and low functional reserve have a negative impact on prognosis, regardless of acute disease. there was agreement between mortality and the physician´s intuitive prognosis. electrochemical methods for diagnosing the severity of patients with multiple trauma introduction: multiple trauma is one of the leading causes of death worldwide [ ] . timely diagnosis and treatment is crucial in this state. one of the promising areas is the use of new electrochemical methods they are simple, flexible, efficient and of low cost. among these methods, attention is paid to the measurement of open circuit potential (ocp) of the platinum electrode and cyclic voltammetry (cva). the ocp is a reflection of the balance of pro-and antioxidants in the body, and the amount of electricity (q) determined by cva is proportional to the antioxidant activity of the biological environment. methods: a total of patients with severe multiple trauma ( . ± . y.o., men and women) were enrolled; apacheii . ± . ; iss . ± . ; blood loss ± ml. blood plasma was collected from patients. measurement of the ocp was carried out according to [ ] , cva analysis -according to the original method on a platinum working electrode. results: a shift in the ocp towards more positive potential values (fig. ) , while the antioxidant activity of blood plasma decreased (fig. ) . a more significant change of ocp, as compared to the q values, may indicate not only a deficiency in the components of the antioxidant defense system of the body, but also an increase in the concentration of prooxidants (e.g., reactive oxygen species), which are involved in oxidative stress. who underwent surgical fixation). information was collected from tarn, icnarc and surgical team databases. our primary outcome was itu resource utilisation (itu los and mechanical ventilation days). our secondary outcomes were morbidity and mortality (hospital los, infection burden, inotrope use and death before discharge). data was collected and analysed in microsoft excel and r. results: patients were included (group = , group = , group = ). mortality was significantly higher when comparing the post groups undergoing conservative ( %, / ) vs. surgical fixation ( %, / ), p-value = . . regarding potential temporal changes, there was no significant difference in mortality between the non surgical groups; pre- (group : / ) and post (group ), p-value . . group patients did spend more time mechanically ventilated (p-value . ) and used more antimicrobials (p-value . ) ( table ) . conclusions: patients undergoing surgical rib fixation at the rlh had significantly improved mortality with more days spent mechanically ventilated. pilot study on ultrasound evaluation of epiglottis thickness in normal adult a osman introduction: as the prevalence of epiglottitis is decreasing due to immunization, the difficulty in early detection remained. the aim of this study is to determine the thickness of epiglottis in normal adult with the utilization of bedside ultrasound. methods: this was a prospective observational study of convenience selection among healthy staff in emergency department, university malaya medical centre. the identification and measurement of epiglottis were performed using a mhz linear transducer by trained emergency physicians and registrars in em. subjects were scanned in either standing or upright seated position with the neck neutral or mildly extended. the epiglottis, thyroid cartilage and vocal cord were visualized and the epiglottis anteroposterior(ap) diameter was measured. difference in categorical parameters were analyzed by independent-sample t-test. the relationship between height, weight and epiglottic size was analyzed using pearson's correlation. results: fifty-six subjects were analyzed with males and females age ranging from to years old. the epiglottis ap diameter ranged from . cm to . cm, with average of . cm. there was significant difference in epiglottic ap diameter between male (m= . cm, sd= . ) and female (m= . cm, sd= . ; t( )= . , p=< . , twotailed). moderate positive correlation between height and epiglottic ap diameter (r= . ) and weight (r= . ) was documented. conclusions: our study demonstrated the identification and visualization of epiglottis was feasible and easy with the use of bedside upper airway ultrasonography. there was a little variation in the ap diameter of epiglottis in adults. indoor vs. outdoor occurrence in mortality of accidental hypothermia in japan y fujimoto , t matsuyama , k takashina introduction: the impact of location of accidental hypothermia (ah) occurrence has not been sufficiently investigated so far. thus we aimed to evaluate the differences between indoor and outdoor occurrence about baselines, occurrence place, mortality, and length of icu stay and hospital stay. methods: this was a multicenter retrospective study of patients with a body temperature ≤ °c taken to the emergency department of hospitals in japan between april and march . we divided the included patients into the following two group according to the location of occurrence of ah (indoor versus outdoor). the primary outcome of this study was in-hospital death. secondary outcomes were the length of icu stay, and hospital stay. results: a total of patients were enrolled in our hypothermia database. there were and patients with the outdoor and indoor occurrence. the indoor group was older ( versus . years-old, p< . ) and worse in adl than the outdoor group. the proportion of in-hospital death was higher in the indoor group than the outdoor group ( . % [ / ] versus . % [ / ], p< . ). the multivariable logistic regression analysis demonstrated that adjusted odds ratio of the indoor group over the outdoor group was . ( %ci; . to . ) ( table ) . as for secondary outcomes, both of the length of icu stay and hospital stay in survivors were longer in the indoor group than the outdoor group. conclusions: our multicenter study indicated that indoor occurrence hypothermia accounts for about % of the total in this study, and the proportion of in-hospital death was higher in the indoor group. we have to raise an alert over the indoor onset accidental hypothermia and need to take countermeasures for prevention and early recognition of ah in indoor location. conclusions: during acute asthmatic attack, arterial hyperlactatemia is frequently present at ed arrival. nevertheless, the plasma lactate level was no significant difference between ed admission and hr after treatment. the introduction: this is a case series of traumatic aortic injury (tai) which was diagnosed by transesophageal echocardiography (tee) in the emergency department. the number of patients with blunt thoracic aorta injury arriving at emergency department is on the rise and survival rate is time-dependent on early diagnosis. tee offers several advantages over transthorasic echocardiography (tte) including reliability, continuous image acquisition and superior image quality. methods: all trauma patients who presented to emergency department from st january until th november at hospital raja permaisuri bainun, perak, malaysia with suspected tai were evaluated with transesophageal echocardiography. over the years period, tee was performed in patients. patients had positive findings suggestive of tai. results: the first case was an old lady who presented after a deceleration injury in a car accident. tee was performed due to hemodynamic instability and found an intimal flap along the ascending aorta. the second case, a stanford type a (figure ) , was complicated with pericardial tamponade. the intimal flap was visualised from the aortic arch extending to the descending aorta by tee. the third case was a case of intramural haematoma involving distal aortic arch extending to the descending aorta which survived until corrective surgery. in the fourth case, tee revealed a motion artefact which mimicked an intimal flap in the ascending aorta. in the fifth case, tee showed intimal flap at aortic isthmus which was not detected by tte. in the last case, a traumatic aortic dissection was complicated by aortic regurgitation (figure ) . conclusions: tee can be a useful point of care tool use by emergency and critical care physicians for early diagnosis of blunt traumatic aorta injury. introduction: reboa is an endovascular intervention intended to preserve central perfusion in the context of shock due to noncompressible torso haemorrhage. more so, it is less invasive than the traditional approach of resuscitative thoracotomy (rt) and aortic crossclamping. though its use dates back to the korean war, it has not been widely adopted in trauma management, as evidence demonstrating clear benefit compared with conventional rt is lacking [ ] . we aimed to evaluate feasibility, outcomes and complications after reboa for haemorrhagic shock and traumatic cardiac arrest. methods: we performed a systematic literature review, searching scopus and pubmed databases using relevant terms (july ). we included studies enrolling patients with haemorrhagic shock or cardiac arrest after civilian trauma who had undergone reboa and reported hospital mortality (our primary outcome). abstract-only studies and single-patient case reports were excluded. we collated and analysed data using review manager v . . the newcastle-ottawa scale was used to assess risk of bias. results: sixteen in-hospital studies met inclusion criteria (n= ). ten were case series and six were cohort studies comparing reboa outcomes with those of rt. there were wide differences between studies' inclusion criteria, case-mix (including cardiac arrest), injury severity, insertion details, and reported outcomes. overall hospital mortality post-reboa was . %. meta-analysis of cohort studies indicated notably lower mortality in patients undergoing reboa (or . , . - . ) than rt with low statistical heterogeneity between studies (i = %), shown in fig . conclusions: whilst our findings are limited by methodological differences and biases in the included studies, almost % of patients undergoing reboa for haemorrhagic shock and/or cardiac arrest survived to discharge. furthermore, reboa appeared to offer a consistent mortality benefit compared with rt. introduction: trauma related coagulopathy remains a primary contributor to mortality on battlefields and in civilian trauma centres. fibrinogen is considered to be the first to drop below critical level and correspondingly compromised coagulation process. however, it is unclear if fibrinogen concentrate at a very early stage is feasible and effective to prevent from coagulopathy. methods: a total of acutely injured patients in austria, germany and czech republic were screened and enrolled in this controlled, prospective randomized placebo controlled double blinded multicentre and multinational trial. upon the completion of randomization, fibrinogen concentrate ( mg/kg, fgtw©, lfb france) or placebo was reconstituted and given to the patients at the scene or during helicopter transportation from the scene to nearby hospitals. blood samples were taken at baseline (scene of accident before study drug administration), at the emergency room, three hours, nine hours and twentyfour hours after admission to the hospital as well as after three and seven days after admission, for measurements of blood gases and coagulation, together with clinical data and outcome records. results: the demographic and injury characteristics and the estimated blood loss, iss, and gcs at the scene were similar in both groups. in the placebo group, fibrinogen concentration dropped from mg/dl at injury site to mg/dl () at er admission and clot stability reduced from . mm ( , mm) to mm (p= . ) (fig ) . fibrinogen concentrate administration prevented the drop of fibrinogen level (baseline of mg/dl to mg/dl and improved clot stability from mm at baseline to mm at er. conclusions: pre-hospital administration of fibrinogen concentrate in traumatic bleeding patients is feasible and effective in preventing the development of coagulopathy. data from this study support the use of fibrinogen to prevent trauma related coagulopathy. fibrinogen concentrate vs cryoprecipitate in pseudomyxoma peritonei surgery: results from a prospective, randomised, controlled phase study results: the per-protocol set included pts (hfc, n= ; cryo, n= ). the mean total intraoperative dose of hfc was . g vs . pools of cryo (containing approx . g of fibrinogen). median duration of surgery was . h. overall haemostatic efficacy of hfc was non-inferior to cryo and was rated excellent or good for % of pts receiving hfc and cryo, with similar blood loss. intraoperatively, only red blood cells were transfused (median: unit). intraoperative efficacy is shown in table . infusions were initiated . h earlier with hfc than cryo due to faster product availability. preemptive hfc led to a greater mean increase vs cryo in fibtem a ( figure ) and plasma fibrinogen (figure ). there were serious adverse events (saes) in the hfc group and in the cryo group, including thromboembolic events (tees; deep vein thromboses, pulmonary embolisms). no aes or saes were deemed related to the study drug. conclusions: hfc was efficacious for treatment of bleeding in pts undergoing surgery for pmp. no related aes and no tees occurred in pts treated with hfc. fig. (abstract p ) . fib mcf t to t with % ci fig. (abstract p ) . fibtem a prior to and following the preemptive dose of hfc/cryoprecipitate introduction: patients in the intensive care unit often suffer from thrombocytopenia. in dealing with this problem, we need to figure out not only the cause of thrombocytopenia but also the risk of bleeding. however, there is no reliable method for evaluating bleeding risk. methods: in this preliminary study, four thrombocytopenic patients who required platelet transfusion before undergoing invasive procedure were enrolled. written informed consent was obtained from all patients for participation in the study. bleeding was graded using the who bleeding scale. thrombogenic activity was evaluated using total thrombus-formation analysis system (t-tas), rotational thromboelastometry (rotem), and multiplate impedance aggregometry. for t-tas analysis, we prepared a novel microchip, named hd chip, which is suited for analyzing low platelet samples rather than those with normal platelet counts. , key patient groups in which it was wasted and the use of standard laboratory tests (slts) to guide its use. the purpose was to assess the potential benefit a point of care viscoelastic haemostatic assay (vha) could have on ffp transfusion and waste. the national blood transfusion committee and nhs blood and transplant committee have published data showing that up to % of ffp is transfused inappropriately [ ] . methods: blood bank data was obtained evaluating haemorrhaging patients in whom ffp was requested across a nine-month period in . patient bleeds were categorised by speciality. the mean time ffp dispensed and wasted was recorded, as were timings of slt requests. where available, the inr result was recorded. results: patients were identified. transfusions were requested. table shows that the highest transfusion requirements are for acute medical emergencies and major trauma. % of transfusion were surgical specialities, it would be expected that these patients would have anaesthetic or critical care input. units were wasted. acute medical emergencies wasted the highest amount of ffp ( units). table demonstrates that . % of transfusions had an inr available one hour prior to ffp being dispensed. conclusions: we conclude that use of slts to guide ffp transfusion is low. this suggests transfusion decisions are being made clinically. a point of care vha could give treating physicians better access to timely haemostatic data. introduction: we developed the process for the out-of-hospital packed red blood cells (prbc) transfusion in the hems of castilla-la mancha clm according to criteria of medical indications, security, monitoring and tracking. haemorrhage is a preventable cause of death among population suffering accidents or bleeding injuries in regions with low population density where health services should reach people in remote areas. hems of clm is the first out-ofhospital emergency service in spain that provides prbc transfusion there where the accident takes place. this program has been developed jointly between hematologists of the center for transfusions ct and the hems team. methods: observational retrospective study with data collected from june to august . the medical helicopter was provided with two prbc o rh(d) negative (fig ) . shock index was selected as indication for transfusion. to achieve feasibility and preservation of the prbc it was established a prospective monitoring and microbiological culture for both groups: case group for the prbc kept in the hems and control group in the hospital (fig ) . controls and comparison of hematologic analysis were performed immediately and days after collection. statistics used spss . (signification p< . ). results: prbc were evaluated, case - control. analyses were tested days and after collection. hemolysis was not observed. all cultures were negative. results obtained of the prbc after days transported in the hems related to monitoring parameters were not different than those observed on prbc conserved in the ct. prbc were transfused to patients in out-of-hospital assistance. neither post-transfusional reactions or undesirable events have been registered. prbc units are changed every days. conclusions: the process designed (collection, conservation, tracking and tests) to make prbc available in the medical helicopter has demonstrated to keep the standard conditions and properties to be transfused in critically ill patients out-of-hospital. outcomes in patients with a haematological malignancy admitted to a general intensive care unit a corner east sussex healthcare nhs trust, intensive care, eastbourne, united kingdom critical care , (suppl ):p introduction: recent published data have challenged the view that critically ill patients with a haematological malignancy have a poor prognosis [ ] . reports have largely originated from tertiary centres. the aim of this audit was to evaluate the intensive care unit (icu), in hospital and one year mortality for a cohort of patients admitted to a mixed medical and surgical icu in a district general hospital. methods: details were obtained for all patients with a haematological malignancy admitted to eastbourne and hastings icu between march and august . patient characteristics, type of malignancy, reason for admission, degree of organ support and survival rates at icu discharge, hospital discharge and year postadmission were collected. results: patients, % male, were identified. median (interquartile range, iqr) age was ( - ) years. % had neutropenia. the commonest malignancies were acute leukaemia %, lymphoma % and myeloma %. reasons for admission were respiratory %, cardiac % and renal %. organ supports used were noradrenaline %, intubation and mechanical ventilation %, renal replacement therapy (rrt) % and dobutamine %. overall survival rates are shown in figure . patients were discharged from hospital following a period of mechanical ventilation. for these patients, median (range) age was ( - ) years. all were male. median (iqr) time in hospital prior to admission was ( - ) days, / patients required vasoactive support, / required rrt, median icu length of stay was ( - ) days. / were admitted following surgery for an unrelated condition. to date, only / patient has survived years post icu admission. conclusions: although survival rates were disappointing, particularly in those patients requiring mechanical ventilation, selected patients have the potential for a good outcome. these results outcomes have been presented to our haematology department to aid patient counselling. analyses. cox regression was used for the survival analysis. organ failure was defined as the occurrence of renal failure based on acute kidney injury network (akin)-creatinine or need for; vasopressors, invasive ventilation or continuous renal replacement therapy (crrt) the first days after admission. length of stay was only analysed in survivors. results: the study included unique patients. prolonged aptt was associated with mortality with a % confidence interval (ci) of hazard ratio . - . . prolonged aptt correlated also with the occurrence of renal failure and the need for vasopressor and crrt with % ci of odds ratio (or) . - . , . - . and . - . (fig ) . increased pt-inr was associated with the need for vasopressors and invasive ventilation with % ci of or . - . and . - . . both aptt and pt-inr correlated with length of stay with % ci of or . - . and . - . . conclusions: activated partial thromboplastin time on admission to the icu is independently associated with mortality. both aptt and pt-inr are independently associated with length of stay and the need of organ support. all regression models were adjusted for saps score which means that aptt prolongation and pt-inr increase on admission represent morbidity that is not accounted for in saps . introduction: the goal was to assess if daily venous thromboembolism (vte) assessment was being done in our critical care (cc) unit, and if not, what changes could be made. a mortality review showed the need for a dynamic vte assessment in cc patients, who are subject to daily changes influencing vte risk. a daily risk assessment was introduced, and a 'tab' on our clinical information system, metavision(r)(mv) was created. recently published national institute for health and care excellence guidelines on vte risk assessment in cc provided us cause to assess our compliance [ ] . methods: data was collected from mv. review of daily vte assessment was made and a percentage completion of daily vteassessments was calculated per patient.interventions were done using standard improvement methods through pdsa cycles. results: baseline data, of patients, was collected in july, .compliance with daily vte assessment was %. the results were presented at the clinical governance forum(cgf), and posters were displayed in cc. the second cycle, of patients, was collected in october. compliance had increased to %.following discussion from presenting results at the cgf, the vte tool was appropriately modified.the responsibility of vte assessment was also shifted to becoming more shared, including all clinical staff, rather than mainly consultants. the third cycle, of patients, was collected in november. compliance had increased to %.introducing a nursing care bundle with vte is in progress. conclusions: despite the identification of a risk in our clinical practice and the development of an appropriate it tool to facilitate improved practice, the advent of new national guidance revealed poor compliance with agreed standards. this shows the difficulties with achieving practice change in complex multiprofessional clinical environments. a sustained effort is required focusing on dissemination and engagement across the whole team. introduction: we describe the changes in anti factor xa (afxa) activity, thrombin generation and thromboelastography (teg) in critically ill patients with and without acute kidney injury (aki) following routine administration of tinzaparin as part of venous thromboembolism (vte) prophylaxis. methods: pilot prospective observational study. patients divided into those with and without aki were administered tinzaparin by subcutaneous injection as per established local guidelines. patients who did not receive tinzaparin were recruited as a 'control'. plasma afxa activity and thrombin generation were measured at intervals over a hour period. teg parameters were collected at t and t . results: afxa activity: results are shown in figure . / patients failed to achieve a prophylactic afxa level of > . at any point. / patients achieved a level of > . however in all cases this was at the lower end of the prophylactic range and was achieved for only a short time (median . hours). / achieved a level of > . for the whole h period. there was no difference between the aki and no aki groups. endogenous thrombin generation: there is no significant difference in thrombin generation between the aki and no aki groups. there is a significant decrease in thrombin generation between h and h (p< . ) and a significant increase between h and h (p< . ) (figure ). there is no significant difference between h and h (p= . ). teg: all teg parameters for all patients were within normal range conclusions: standard vte prophylactic dose tinzaparin rarely achieves an afxa range that has been suggested for vte prophylaxis. however, as assessed by thrombin generation, a hypo-coagulable state is generated in response to lmwh. there is no difference between critically ill patients with or without aki that would suggest the need for dose reduction in this context. (abstract p ) . thrombin generation at h, h and h. t = time of tinzaparin administration, with the sample taken just prior to administration. patients from aki group shown with dotted line and from no aki shown with solid line % which takes the third place between cpb-associated complications . current data demonstrates the importance of researching of changes in haemostatic system in paediatric patiens after cpb. provided below data is an intermediate result of our research. methods: patients in age up to mohth days (median age - , months, youngest age - days after birth, oldest - months days), who underwent cardiac surgery with cpb to treat congenital heart diseases, were enrolled in this study. all patients were divided into two groups: stwithout tc, ndwith tc. protein c (pc) and fibrin-monomer (fm) plasma levels were assessed in there points: before surgery, -hours and hours after surgery. thrombotic cases were provided by doppler ultrasound or mri. results: thrombotic complications were diagnosed in chidren ( %). between all tc ischemic strokes were diagnosed in % ( cases), arterial thrombosis in % ( cases), intracardiac thrombus in % ( cases). in group with tc fm-mean values in points , and respectively were . ; and mcg/ml, meamwhile in group without thrombosis - . ; . and . mcg/ml .pc-mean value in st groupwere ; and %, in the nd group - ; and % respectively in the points , and . statistically significant differences between groups in rd point (p< . ) and correlation between pc and fm (r=- . ; p< . ) were detected. conclusions: cpb causes hypercoagulation with increasing of pc consumtion and fm level. moreover, cp associated with a high risk of tc on the rd day after cardiac surgery. further studies to investigate prognostic values of fm and pc in thrombosis are required. these studies would help to asses fm and pc as markers of tc and possibility of pc-prescribing for prevention and treatment of these complications. introduction: thrombocytopenia is a common condition in critically ill patients and an independent predictor of mortality. the relevance of a supranormal platelet count remains unclear. septic patients with disseminated intravascular coagulation (dic) are also known to have a high mortality, but the influence of sepsis on mortality rates in coagulopathic patients is less well characterised. our objectives were to: ) evaluate mortality amongst patients with sepsis and nonsepsis associated dic. ) assess incidence of dic during the first days of admission. ) assess the relationship between platelet count and mortality. methods: records of adult critical care patients admitted to the royal liverpool university hospital between - were retrospectively reviewed. the presence of sepsis (using the definition of sirs with infection), coagulopathy, degree of thrombocytopenia and day mortality were noted. modified isth dic score was used to define dic. results: the overall mortality rate was %. patients were identified as having sepsis ( %) and non septic patients ( %). mortality rates of patients with sepsis were significantly higher than without sepsis ( % vs % respectively, p< . ). in patients with dic, their dic scores tended to be 'positive' for the first days of admission. fibrin-related markers were often not available for dic scoring. mortality rates amongst patients with sepsis-associated dic were greater than patients with non-sepsis related dic. thrombocytopenia severity was associated with mortality, and patients with platelets above the upper limit of normal had lower mortality rates ( % when platelets > x ^ /l, % when platelets < x ^ /l). conclusions: sepsis-associated coagulopathy is associated with a higher mortality rate than non-sepsis associated coagulopathy. supranormal platelet counts may be associated with a mortality benefit. introduction: deep vein thrombosis (dvt) is a major problem in icu and affects overall lethality. dvt is widespread complication in icu, especially in elderly patients, when early activisation may not be achieved. aim of this study is comparison of haemostatic potential and analgesia methods of elderly patients who underwent major urological surgery during their stay in icu. methods: a cross-sectional study was employed. participants were ≥ y.o., underwent major urological surgery, have had normal initial hemocoagulation data (thromboelastography was performed to all of them), had received analgesia with epidural catheter or iv by opioids use and were treated in icu > days due to non-coagulopathy states, were included. data were collected from october till october . the patients were examined with thromboelastograph "mednord" for thromboelastogramm (teg) and with esaote usg for thrombi occurrence in lower limb deep veins. the anticoagulants were prescribed under the esa guidelines . results: participants (n= ) were divided in two groups -non-opioid analgesia with epidural catheter (n= ) and opioid analgesia (n= ). we received moderate decrease in anticoagulants dosage to the patients with epidural analgesia with the same teg goals compared to the patients with opioid analgesia. other factors as comorbidities may provoke dvt events, but was not evaluated in this study. the dvt events were monitored by expert with the use of usg to locate thrombi in the vein. conclusions: use of epidural catheter analgesia provides moderate decrease of anticoagulants dosage compared to opioid analgesia patients; however strict control of teg data must be presented. comorbidity need to be monitored for early detection and prevention of dvt events. introduction: patients with morbid obesity (mo) have a high risk of thromboembolic events. in patients with a bmi > , the hypercoagulable state is due to impairment of all parts of the blood coagulation as well as anticoagulation mechanisms by obesity. methods: the hemostasis system was studied in patients with a bmi> kg/m with various pathologies that were admitted to icu. all patients were divided into groups depending on the type of therapy: group (n= ) received monotherapy with enoxaparin sodium . % . ml sc times a day every h; group (n= ) received combination therapy with enoxaparin sodium . % . ml sc times a day every h and pentoxifylline mg times a day every h. to study the hemostasis system, we used lpteg immediately after hospitalization, on , , days. results: in both groups, prior to treatment: contact coagulation intensity (icc) was increased by . %, intensity of coagulation drive (icd) -by more than . %, clot maximum density (ma) -by . %, index of retraction and clot lysis (ircl) - . % above normal. patients of the st group: icc increased by . %, icd was close to normal values, ma increased by . %, ircl was increased by . %. patients of the nd group on the th day: icc decreased by . % compared with the norm; the coagulation and fibrinolysis parameters were close to normal values and the decrease in fibrinolysis activity reaches to normal. conclusions: combined therapy of thromboembolic complications in patients with obesity sodium enoxaparin sodium and pentoxifylline is more effective than enoxaparin sodium monotherapy because it affects all parts of the hemostatic system. introduction: a laryngeal injury secondary to blunt neck trauma can lead to life-threatening upper airway obstruction [ , ] . ultrasound enables us to identify important sonoanatomy of the upper airway [ ] . the purpose of this report is to discuss role of pocus airway in blunt neck trauma and to determine airway management based on standard schaefer subgroups classification. methods: three cases of blunt neck trauma presented to our centre with either subtle or significant clinical signs and symptoms. standard airway management was performed prior to pocus airway using mhz linear transducer and it findings were later compared to flexible fibreoptic laryngoscopy and computed tomography (ct). results: pocus airway had identified one out of cases to have schaefer and the remaining as schaefer . all pocus airway findings were confirmed with flexible fibreoptic laryngoscopy and ct scan (figs , ) . based on schaefer, supportive care and early steroid administration are advisable for group and . for groups to , immediate open surgical repair is deemed necessary due to extension of injuries.all cases were intubated using glidescope.all including those presented with schaefer were managed conservatively and discharge well with proper follow-up. conclusions: upper airway ultrasound is a valuable, non-invasive and portable for evaluation of airway management even in anatomy distorted by pathology or trauma. an organised approach using pocus airway as an adjunct can expedite care and prevent early and long term complications in facilities without flexible laryngoscope and ct. introduction: high-flow nasal oxygen (hfno) and helmet noninvasive ventilation (hniv) are increasingly used for the early management of acute hypoxemic respiratory failure (ahrf). we compared the physiological effects of hfno and hniv during ahrf. methods: in this randomized cross-over study, we enrolled patients with acute-onset (< days), non-cardiogenic respiratory distress (respiratory rate> /min), pulmonary infiltrates at the chest-x-ray and hypoxemia (spo < % while breathing on room air). all patients received hniv (peep cmh o, pressure support adjusted to achieve a peak inspiratory flow of l/min) and hfno (flow l/min) for one hour each, in a randomized cross-over manner. at the end of each period, arterial blood gases, inspiratory effort (esophageal pressure) and respiratory rate were recorded. self-assessment of dyspnea and device-related discomfort ( [ ] [ ] [ ] [ ] [ ] ). conclusions: as compared to hfno among critically ill patients with ahrf, hniv ameliorates oxygenation, limits inspiratory effort and relieves dyspnea, without affecting paco , respiratory rate and comfort. introduction: pre-intubation hypoxemia is a predictor of negative patient outcomes including in-hospital mortality. while successful first intubation attempt is also an important factor of patient outcomes, little is known about whether physicians achieve successful first intubation attempt for the hypoxemic patients in the emergency department (ed). the aim of this study is to investigate the first-pass success for patients with pre-intubation hypoxemia in the ed. methods: this is an analysis of the data from the second japanese emergency airway network study (jean- study)a multicenter, prospective, observational study of eds in japan. we included all patients who underwent intubation in the ed from through . we excluded patients ) aged < years and ) patients who underwent intubation for cardiac arrest. we grouped pre-intubation hypoxemia as follows: non-hypoxemia (oxygen saturation [spo ], ≥ %), moderate-hypoxemia (spo , %- %), and severehypoxemia (spo , < %). primary outcome was the first-pass success rate. to demonstrate the association between pre-intubation hypoxemia and the first-pass success in the real-world setting, we fit two unadjusted logistic regression models ) using grouped preintubation hypoxemia as a categorical variable and ) using the preintubation spo as a continuous variable. results: among , patients who underwent intubation in the ed (capture rate, %), , patients were eligible for the analysis. compared to the non-hypoxemia, the first-pass success rate was low in moderate-hypoxemia ( % vs %; or= . [ %ci, . - . ]) and severe-hypoxemia ( % vs %, or= . [ %ci, . - . ]). additionally, there was a linear association between pre-spo and lower first-pass success rate (or for the success, per one pre-spo decrease, . [ %ci, . - . ]). conclusions: based on the large, multicenter data, the first-pass success rate was low in hypoxemic patients compared to nonhypoxemic patients in the ed. introduction of rapid-sequence induction guideline to reduce drug-associated hypotension in critically unwell patients introduction: the aim of this project was to assess whether the introduction of a rapid sequence induction (rsi) agent guideline changed drug choice and the incidence of peri-intubation vasopressor use at st john's hospital, livingston. it is well documented that emergency airway management in the critically ill can be a source of significant morbidity and mortality [ , ] and the choice of induction agent matters [ ] . methods: an rsi agent guideline was instituted for all critically ill patients being intubated in icu and the ed [ figure ]. following this, we set up an intubation registry to collect data from all intubation events. this data was then compared to a previous audit of intubations completed in . results: the choice of agent used pre-and post-intervention are summarized in figure . forty-five intubation events were included in the initial audit in , of which, ( %) required vasopressor support immediately following intubation. of the intubation events following the guideline's introduction, ( %) required vasopressors. ketamine use changed from % to %, propofol use from % to % and midazolam from % to %. thirty-eight of these intubation events ( %) were compliant with the guideline. conclusions: the introduction of the rsi guideline dramatically affected the choice of induction agent and reduced the incidence of significant hypotension requiring vasopressors ( % versus %). overall compliance with the guideline was excellent ( %). introduction: the purpose is to test the feasibility of using the i-gel® device for airway maintenance during bronchoscopic-guided percutaneous dilatational tracheostomy (pdt). usually pdt is accomplished via the tracheal tube. failure to position the endotracheal tube correctly can result in further complications during the procedure. the alternative implies extubation and reinsertion of an i-gel® airway device. methods: the pdt was performed using the blue dolphin method in patients in intensive care unit. before undertaking bronchoscopicguided percutaneous dilatational tracheostomy (pdt), the patient's tracheal tube (et) was exchanged for i-gel®, as a ventilatory device for airway maintenance. the insertion of the i-gel®, the quality of ventilation, the blood gas values, the view of the tracheal puncture site, and the view of the balloon dilatation were rated as follows: very good ( ), good ( ), barely acceptable ( ), poor ( ), and very poor ( ) [ ] . results: the i-gel® successfully maintained the airway and allowed adequate ventilation during percutaneous tracheostomy in all patients. the ratings were or in % of cases with regards to ventilation and to blood gas analysis, for identification of relevant structures and tracheal puncture site, and for the view inside the trachea during pdt. conclusions: the i-gel® successfully maintained the airway and allowed adequate ventilation during percutaneous tracheostomy in all patients. the ratings were or in % of cases with regards to ventilation and to blood gas analysis, for identification of relevant structures and tracheal puncture site, and for the view inside the trachea during pdt. no damages to the bronchoscope, reports of gastric aspiration or technical problems were detected. the bronchoscopic view obtained via an i-gel® seems to be better than that obtained through an endotracheal tube (et) or through traditional laryngeal mask [ ] . introduction: the purpose of this study was to investigate the efficiency of nasal airway inserted in the oral airway (on airway) in securing the airway patency during mask ventilation [ ] (fig ) . methods: fifty eight patients undergoing general anesthesia were randomly assigned to either oral airway group (group o) or on airway group (group n). in both group, mg/kg of propofol was infused intravenously and mask ventilation was performed in the sniffing position without head extension or jaw thrust. the patients were ventilated with a volume-controlled ventilator with o flow of l/min, tidal volume of ml/kg (ibw), and respiratory rate of /min. before the start of mask ventilation, airway was placed in the oral cavity. oral airway was used in group o and on airway was used in group n. peak inspiratory pressure (pip), tidal volume and etco were compared between the two groups. the location of airway tip was graded by fiberoptic bronchoscope as; : airway obstructed by tongue, : epiglottis visible, : airway touches epiglottis tip, : airway passes beyond epiglottis tip [ ] . methods: a prospective uncontrolled observational study in - in ukrainian hospitals. sma-pts from - mo were involved. all pts. ready for extubation: afebrile, no infiltrations on chest x-ray, normal wbc. however, each sma-pts. failed sbt (t-tube or psv). we evaluated: extubation success (no reintubation in hours), icu los, one year survival. three pts. were excluded: two pts. by staff decision, family have choosen tracheostomy. sma-pts. included. a cuff leakage test performed -with a negative, dexamethazone mg iv was administered. after extubation niv was started by ventilogik ls in st mode via nasal mask giraffe. the epap and ipap settings were titrated to reach the chest excursion and target levels of spo ( - %) and etco ( - mmhg). a sputum was draining by mechanical insufflation-excuflation (mie) and aspirator results: all pts, were extubated successful. the mean icu los was . days ( - days), one year survival rate was %, respiratory failure fully compensated by niv, there was no icu admission. every sma-pts. are in good condition, gaining weight introduction: aerosol delivery has previously been assessed during simulated adult hfnt, delivered by various stand-alone humidification systems [ ] . the objective of this study was to evaluate aerosol delivery during simulated hfnt delivered by a mechanical ventilator, across three clinically relevant gas flow rates. methods: ml of mg/ml salbutamol was nebulised using an aerogen solo nebuliser (aerogen, ireland). an adult head model was connected to a breathing simulator (asl , ingmar, us), vt ml, bpm and i: e, : (fig ) . hfnt was supplied via the servo-u ventilator (maquet, getinge, sweden), using the integrated nebulisation option. tracheal dose was recorded at two nebuliser positions; a (after the humidification chamber) or b (before of the cannula), at three gas flow rates ( lpm, lpm and lpm) (n= ). the mass of drug captured on a filter placed distal to the trachea (tracheal dose) was quantified using uv spectroscopy at nm. results: presented in table . conclusions: to our knowledge, this is the first study to successfully demonstrate aerosol delivery during simulated hfnt, delivered by a mechanical ventilator. increasing gas flow rate was associated with a reduced tracheal dose (p= < . ). at lpm, a significantly greater tracheal dose was observed when the nebuliser was positioned before the nasal cannula (p= < . ). at lpm, a greater tracheal dose was yielded when the nebuliser was positioned after the humidifier (p= < . ). introduction: tracheotomies are often performed in critically ill patients who are in need of prolonged mechanical ventilation and respiratory care. our aim was to evaluate the possible effect of percutaneous and surgical tracheotomies on thyroid hormone levels. methods: eighty seven adult patients were included in our study from january to september . patients were in need of prolonged mechanical ventilation and tracheotomies were performed after consent was taken. we have excluded patients with preexisting thyroid diseases. forty five patients were undergone percutaneous tracheotomies and forty two patients were undergone for surgical. thirty eight female patients and forty nine male, age range - . we studied tsh, t and ft serum levels using chemiluminescence immunoassay method before either procedure and hours post each procedure.: statistical analysis was performed using spss . significance was estimated at the level of p< . results: tsh levels were increased in surgical group compared to percutaneous group at hours post procedure but the difference was not found statistically significant (p> . ). the rise in post operative levels of t compared to preoperative was found statistically significant for surgical tracheotomy group (p< . ).elevated ft levels for both groups have shown statistically significant difference between preoperative and postoperative period for the surgical tracheotomy group (p< . ) conclusions: we analyzed the effect of surgical versus percutaneous tracheotomy on thyroid hormones and it was found that both introduction: insertion of a tracheostomy for weaning purposes is associated with prolonged critical length of stay (los) and several adverse patient outcomes [ ] . previous work has suggested that protocolised weaning may reduce weaning times [ ] . we aimed to assess the impact of protocolised weaning on los following introduction of a standardised weaning protocol in . conclusions: introduction of a standardised weaning protocol for patients with a tracheostomy in our unit has had a beneficial effect on several patient outcomes, notably duration of weaning and length of critical care admission. introduction: delirium is a relatively frequent neurologic complication in liver transplantation (lt) recipients, which is an important cause of increased morbidity, mortality, extended icu stay, and increased cost of medical care. extubation of the endotracheal tube at an appropriate timing is an essential part of intensive care after lt, suggested to improve graft perfusion and systemic oxygenation, and thus decrease intensive care unit (icu) stay and positively affect prognosis. the aim of this study was to compare the incidence of delirium between early and late extubation groups after lt. methods: medical records from patients who received lt from january to july in a single university hospital were retrospectively reviewed. patients were divided into groups: those who underwent early extubation after lt (group e, n = ) and those who underwent extubation within few hours of icu admission after surgery (group c, n = ). the data of patients´demographics, perioperative management, and postoperative complications were collected. early extubation was defined as performing extubation in the operating room after lt. a propensity score matching analysis was performed to minimize the effects of selection bias. results: postoperative delirium occurred in / ( . %) in group e and / ( . %) in group c, respectively (p = . ). after propensity score matching, there was no difference in icu stay (p = . ), time to discharge after surgery (p = . ), and incidence of delirium between groups (p = . ). conclusions: although this study is retrospective in nature, limited by small sample size, early extubation did not affect the incidence of delirium after lt. further prospective studies on this area are required. weight estimation and its impact on mechanical ventilation settings in queen elizabeth hospital intensive care unit a nasr, a iasniuk, a roshdy queen elizabeth hospital, icu, london, united kingdom critical care , (suppl ):p introduction: documented weight in the intensive care unit (icu) can be the total, ideal, adjusted or predicted body weight (pbw). lung protective ventilation depends on tidal volume (vt) delivery which is based on accurate calculation of patients´weight [ ] . the weight is most probably documented on admission to the icu using estimation or one of many available equations. the aim of this study is to assess the documented versus the pbw and its impact on tidal volume delivery for mechanically ventilated patients in queen elizabeth hospital icu. methods: data was collected prospectively from all ventilated patients over a period of weeks in june . vt delivered in the first hour was calculated for each patient. documented body weight and height of each patient was obtained from the nursing chart. pbw was calculated and compared with the documented weight. the difference in vt attributable to the difference in weight has been subsequently calculated. results: ventilated patients were included ( males). the mean tidal volume delivered according to the documented body weight was . ml/kg versus . ml/kg based on pbw. vt more than ml/ kg was delivered in % of patients based on documented weight versus % when correcting the weight according to the pbw equation. conclusions: inaccuracy in documenting weight on patients´admission to the icu is a potential cause of delivering unsafe tidal volume [ ] . the harm can extend to drug dosage, nutrition provision and renal replacement therapy. introduction: ventilator-associated pneumonia (vap) is the leading cause of death among mechanically ventilated critically ill patients [ ] . chest radiography (cxr) is essential in the diagnosis of vap. in the past decade lung ultrasonography has proven to be a valuable tool in the diagnosis and monitoring of lung diseases. the aim of the study is to assess sensitivity and correlation between cxr, lung ultrasound and clinical pulmonary infection score (cpis). methods: in this retrospective, non-randomized study seven patients with proved vap were enrolled. in all patients cpis and lung ultrasound score (lus) [ ] were assessed. comparison of patients that had lus≥ and cpis≥ points was performed. the correlation between lus and cxr was done using the pearson model. results: we found significant difference between positive cxr patients with lus≥ and cpis≥ ( % vs %, p< . ). there is a very high correlation between cxr and lus. these results render lung ultrasound as a highly sensitive tool in the diagnosis of vap. conclusions: our study shows that lung ultrasonography could be used as a reliable supplementary method in the diagnosis of vap. the benefits of lung ultrasound include the ability to perform it at the patient´s bed without need for transportation, no radiation exposure and repeatability. the high correlation between cxr and lung ultrasound makes echography a valuable adjunct in the diagnosis of vap. color introduction: it is difficult to differentiate between pneumonia and atelectasis as cause of lung consolidation in intensive care unit patients. tools like the clinical pulmonary infection score are of little help (sensitivity % and specificity % for detecting pneumonia) [ ] . the objective of this study was to determine the accuracy of ultrasound assessed vascular flow within the consolidation to distinguish these causes. methods: adult patients with pulmonary symptoms and lung consolidation on lung ultrasound that were scheduled for chest-ct were included. vascular flow was analyzed with color doppler imaging (flow velocity scale was chosen at . m/sec.). the final diagnosis made by the treating physician was regarded as the gold standard. results: patients were included of which nine ( %) were diagnosed with pneumonia. vascular flow in the consolidation was present in seven ( %) out of nine patients with pneumonia, compared to three out of ( %) patients with atelectasis (p = . ). the diagnostic accuracy in differentiating between pneumonia and atelectasis was %. the sensitivity and specificity were % and % respectively. the positive predictive value was % while the negative predictive value was %. conclusions: vascular flow in lung consolidations assessed by lung ultrasound in icu patients aids in differentiating between pneumonia and atelectasis. it outperforms the frequently used clinical pulmonary infection score. methods: three intubated patients for various causes of respiratory distress undergoing mechanical ventilation were subjected to tee. at the level of mid-esophagus, the descending aorta short-axis view ( °) the imaging plane is directed through the transverse axis of the descending aorta. sector depth was increased to image the left pleural space beneath the aorta. for the right lung, the tee is rotated to the right at the level of atria until lung is seen or until the image of the liver is seen and the probe was withdrawn until the right lung is seen. recruitment manoeuvres were performed after identifying pbl atelectasis. atelectatic lungs were visually observed to open up during and after the recruitment manoeuvres. results: the time to acquire the image of pbl atelectasis from the time of insertion by tee is short. the images of posterior lung and the effect of lung recruitments is successfully viewed (fig ) . no immediate complication seen. conclusions: tee provides an excellent view of pbl atelectasis and able to directly monitor the success and failures of recruitment manoeuvres. introduction: high respiratory driving pressure (Δ prs) is strongly associated with increased risk of lung injury and increased mortality during mechanical ventilation. Δ prs consists of the pressure required to distend the lung the transpulmonary driving pressure (Δ pl) and the pressure required to distend the chest wall. Δ pl is the pressure that increases the risk of lung injury. data on Δ pl is limited because its measurement requires an esophageal catheter. we aimed to assess changes in Δ prs and Δ pl during proportional assist ventilation (pav+) at different experimental conditions. methods: we retrospectively analyzed patients ventilated with pav+ who had esophageal pressure measurements before and after dead space or chest load addition. we calculated end-inspiratory plateau pressure (pplateau), Δ prs, respiratory system compliance (crs) and Δ pl during occluded breaths in pav+ (figure ). data were compared with wilcoxon signed rank test and p value< . was considered significant. results: patients were analyzed. dead space increase ( patients) did not affect the studied parameters. chest load ( patients) significantly increased pplateau (p= . ) and Δ prs (p= . ) and decreased crs (p= . ) but Δ pl remained the same (p= . ). median (iqr) changes were . ml/cmh o ( . - . ) for crs, . cmh o ( . - . ) introduction: particle flow in exhaled air from mechanically ventilated patient's mirrors the opening and closing of small airways and can be detect by optical particle counter [ ] . we hypothesized that this particle flow is affected by cardiac function. methods: exhaled air from mechanically ventilated patients was analyzed using a customized optical particle counter pexa, figure . introduction: we assessed the diagnostic accuracy of mechanical power (mp) and driving pressure (dp) alone and combined with stress index (si) to identify ventilator settings likely to produce ventilator induced lung injury caused by tidal hyperinflation [ ] [ ] [ ] . methods: secondary analysis of a previous database of ards patients [ ] . computerized tomography markers of tidal hyperinflation (were used as a "reference standard". analysis of the area under the receiver-operating characteristics curve (auc) was used using a two-fold cross-validation. results: in a cluster of patients, a "training set" of not hyperinflated patients was compared with a "validation set" of hyperinflated patients. (figure - ) . conclusions: si seems to be more accurate than mp and dp in identifying tidal hyperinflation in patients with ards. specificity and sensibility were not improved combining si with mp or dp. the introduction: the pao /fio (p/f) ratio is widely used to assess the severity of lung injury. conceptually, the p/f ratio should be independent of the fio and solely depend on the pulmonary condition. however, effect of fio modulation on the p/f ratio has not been well characterized in ventilated intensive care (icu) patients. the purpose of the present study was to investigate the relationship between fio and the p/f ratio in icu patients on mechanical ventilation. methods: in a prospective, interventional study patients with a swan ganz catheter in situ were included. the p/f ratio was calculated at fio levels ranging from . to . with minute intervals. during the study other ventilator settings were not modulated. to understand the physiological effects of fio modulation on gas exchange and hemodynamics, mixed venous oxygen saturation and cardiac output were assessed. shunt fraction was calculated as described by west [ ] . results: patient characteristics and ventilator settings are reported in table . all patients were admitted to the icu after elective cardiac surgery. modulation of fio did have a significant effect on the p/f ratio, following a u-shaped pattern (p < . ) (figure ). the shunt fraction varied with altering fio levels, also exhibiting a u-shaped pattern (p < . ) (figure ). cardiac output was not affected by fio . conclusions: in contrast to current thinking, the p/f ratio varied substantially with altering fio levels in mechanically ventilated icu patients. this is an important novel physiological observation. in addition, it demonstrates that the assessment of the severity of respiratory failure by using the p/f ratio should be standardized to a fixed fio level. conclusions: in patients undergoing prolonged mechanical ventilation, we must take into account all the factors that may affect our patients. the assessment of diaphragmatic dysfunction is key to preventing weaning failure. an optimal level of consciousness as well as a good management of secretions are key to a successful weaning. prognostic value of the minute ventilation to co production ratio as a marker of ventilatory inefficiency in the icu r lopez , r pérez , Á salazar , i caviedes , j graf introduction: ventilatory inefficiency for co clearance may provide better severity stratification in acute respiratory failure than oxygenation [ ] . ventilatory inefficiency (vi) is best assessed by the bohr-enghoff physiological dead space [ ] . we recently reported that the minute ventilation to co production ratio (ve/vco ), a simplified vi index from exercise testing that obviates the paco measurement, correlates better than other vi indices to physiological dead space in mechanically ventilated patients [ ] . here we report the prognostic performance of this index using a survival analysis. mean±sem ve/vco was higher in patients who died than those who survived ( ± vs ± , p< . , figure ). we found a ve/ vco cutoff value of . mortality was higher in patients with high-ve/vco (≥ ) as compared to those with low-ve/vco ( % vs %, p= . ) with an odds ratio of . [ %-ci . - . ]. cumulative mortality was higher in the high-ve/vco than in the low-ve/vco group (log-rank p= . , figure ). conclusions: in this unselected cohort of mechanically ventilated patients an early high ve/vco ratio was associated to -days mortality. the ve/vco ratio may be a simple and non-invasive vi index with prognostic value in this population. introduction: sodium thiosulfate (sts) is a clinically relevant and safe hydrogen sulfide donor that improved acute lung injury (ali) and brain ischemia/reperfusion injury in previous studies [ , ] . methods: in a prospective, controlled, randomized, and doubleblinded trial, twenty adult, anesthetized, mechanically ventilated and surgically instrumented swine with preexisting coronary artery disease [ ] underwent h of hemorrhagic shock (hs; removal of % of the calculated blood volume and subsequent titration of mean arterial pressure to mmhg). post-shock resuscitation ( h) comprised re-transfusion of shed blood, crystalloids, and norepinephrine. animals were randomly assigned to "placebo" or "sts" ( . g·kg - ·h - for h). before, at the end of and every h after shock, hemodynamics, blood gases, and lung function were recorded. results: survival rates did not differ between groups. sts-infusion attenuated the hs-induced impairment of lung mechanics and pulmonary gas exchange (table , ), resulting in a significantly higher horovitz/peep-ratio ( figure ). conclusions: sts during acute resuscitation from hs may protect comorbid swine against hs-induced ali. introduction: alveolar epithelial cell (aec) death is a main mechanism of severe respiratory failure in acute respiratory distress syndrome (ards). classically, cell death is classified into necrosis or apoptosis. recent studies have reported that not only apoptosis but also certain types of necrosis are molecularly regulated and that these regulated necrosis can be therapeutic targets for various diseases. however, the relative contribution of necrosis and apoptosis to aec death in ards has not been elucidated. our study aimed to elucidate which type of cell death is dominant in aec death and to evaluate whether the regulated necrosis is involved in lps-induced experimental ards. methods: we established ards model by instilling μ g of lps intratracheally to mice. to estimate the relative proportion of apoptosis and necrosis in aec death, we measured cytokeratin m level (total cell death marker) and m level (apoptosis maker) in bronchoalveolar lavage fluid (balf) by elisa, and quantified propidium iodide-positive necrotic cells and tunel-positive apoptotic cells in the lung sections. moreover, we performed pathway enrichment analysis of gene expression data from pcr array to evaluate whether regulated necrosis pathway is associated with the ards model. results: both m and m levels were increased in the ards mice. the m /m ratio (an indicator of the proportion of apoptosis to total cell death) in the ards mice was significantly lower than that of healthy controls. moreover, the number of propidium iodidepositive necrotic cells was significantly higher than that of tunelpositive apoptotic cells in ards mice. in the pathway enrichment analysis, the necroptosis pathway, a regulated necrosis pathway, was associated with lps-induced experimental ards. conclusions: aec necrosis is more dominant than apoptosis in lpsinduced ards model. moreover, necroptosis may contribute to ards pathogenesis. aec necrosis including necroptosis is a potential therapeutic target for ards. clinical ards diagnosis is not associated with a unique circulating neutrophil cell surface phenotype t craven , s duncan , s johnston , c haslett , k dhaliwal , t introduction: acute respiratory distress syndrome (ards) is a form of non-cardiogenic oedema due to alveolar injury secondary to an inflammatory process. the clinical diagnosis is defined by the berlin criteria but this may not reflect the underlying biological process. the activated neutrophil is central to the pathogenesis of ards, characterised by altered cell surface markers. methods: three cohorts of seven participants were recruited. the first cohort suffered from mild, moderate or severe ards as defined by the berlin criteria [ ] . the second cohort was composed of ventilated patients on the intensive care unit with acute inflammatory lung disease (diagnosis of clinical suspicion) but did not meet the berlin criteria for ards. a third cohort was composed of age and sex matched healthy volunteers. procurement of human tissue was approved by a regional ethics committee ( /ss/ or /s / or amrec: -hv- ) and with the informed consent of the participant or their personal legal representative. patients were excluded if aged under or over years of age, were expected to survive for less than hours, if the attending physician refused, due to the absence of suitable indwelling vascular catheter, if the haemoglobin concentration was below . g/dl, or if the patient was enrolled in a trial of novel anti-inflammatory agent. whole blood (lysed erytocytes) underwent flow cytometry to determine cd b, , b, , l and . results: a description of the enrolled cohorts can be found in table . there were no significant differences between the mechanically ventilated, critically ill cohorts for any cell surface molecule in the multiplicity adjusted p values (fig ) . the results support the conjecture that clinical diagnostic criteria should not be used as a surrogate to stratify patients according to biological changes, with implications for the testing of biological therapies. introduction: aim of the present study was to compare the global and regional diagnostic accuracy of lung ultrasound (lus) compared to lung computed tomography (ct) scan in patients with the acute respiratory distress syndrome (ards). ards is characterized by a diffuse, inhomogeneous, inflammatory pulmonary edema. lung ct scan is the reference imaging technique, but requires transportation outside the intensive care and exposes patients to x-rays. lung ultrasound (lus) is a promising, inexpensive, radiation-free, tool for bedside imaging. methods: lung ct scan and lus were performed at peep cmh o. lus was performed using a standardized assessment of regions per hemithorax: superior and inferior; anterior, lateral and posterior. each region was classified for the presence of normally aerated, alveolar-interstitial syndrome, consolidation regions and pleural effusion. agreement between the two techniques was calculated, and diagnostic parameters were assessed for lus using lung ct as a reference. both a global and a regional analysis were performed. results: thirty-two sedated and paralyzed ards patients (age ± years, bmi . ± . kg/m and pao /fio ± ) were enrolled. global agreement between lus and ct was . ± . . the overall sensitivity and specificity of lus are shown in table . similar results were found with regional analysis (anterior/lateral/posterior lung regions is a common practice in our icu. during the interruption eit belt was positioned. when the presence of spontaneous breathing activity was evident by clinical assessment and ventilator traces analysis, nmba were administered to reach full paralysis, in accordance with the treating physician. eit tracing were analyzed offline and the change in eeli after nmba bolus, as compared to before nmba administration, was measured. respiratory mechanics and arterial blood gas (abg) data were collected results: we enrolled ards patients, undergoing controlled mechanical ventilation with muscle paralysis. baseline respiratory mechanics and abg data are shown in table . in out of patient the bolus of nmba led to an increase of eeli. in case, the nmb administration led to no changes in eeli. the mean change in eeli was ± ml conclusions: in our small population of ards patients, the administration of a bolus of nmba after the regain of spontaneous breathing activity led to an increase in eeli in out of patients. further study are needed to ) correlate this increase to global and regional respiratory system compliance and ) correlate this increase to the time needed to wean the patient from nmba introduction: to analyze the use of the orthostatic board as an auxiliary device for the treatment of severe ards by assessing its risks and benefits. methods: we selected patients, females and males, hospitalized in a neurological icu, between june and july , in a physiotherapeutic follow-up with diagnosis of severe ards. the patients were submitted to orthotics assisted for to minutes and monitored hr, pam, fr, sato at °and °of inclination and the pao / fio ratio after the procedure. the mean number of sessions per patient was . . all patients were undergoing anticoagulation in rass - , in the treatment of the cause of ards. the mean time of mechanical ventilation was . days. results: among the patients selected, . % presented tachycardia above bpm, requiring intervention in . % and interruption of the procedure in . %. pam arterial hypotension < mmhg was observed in . %, requiring intervention (increase of vasopressor dose and / or change of plank angulation) in % and interruption of the procedure in . %. hypoxemia sato < % was observed in . %, without interruption, but an improvement in pao / fio was observed in only . % of the patients. conclusions: assisted orthostatism as an auxiliary device for the treatment of severe ards was shown to be an alternative, with improvement of pao / fio in . % of the patients, safe and without significant hemodynamic repercussions that could lead to interruption of the procedure. introduction: the eolia trial found that vvecmo compared to conventional mechanical ventilation (cmv) did not improve mortality in patients with severe ards [ ] . the cmv strategy consisted of airway pressures below cmh o. in patients with severe ards higher airway pressures are required to maintain lung aeration. grasso et al. measured the transpulmonary pressure (p l ) in patients with severe ards and increased peep until p l was cmh o, accepting airway pressures above cmh o. fifty percent of patients responded to an increase in airway pressure and did not require vvecmo [ ] . we hypothesized that a p l guided open lung concept (olc) improves oxygenation and prevents conversion to vvecmo in patients with severe ards. methods: a retrospective study was conducted in a tertiary referral icu. the records of patients referred to our icu for advanced medical care were reviewed. inclusion criteria were severe ards according to the berlin definition and the eolia trial inclusion criteria for vvecmo. results: mechanical ventilation was limited to a p l of < cmh o instead of plateau pressures below cmh o. the p l guided olc resulted in an increase in p/f ratio and none of the patients required vvecmo. during the first hours peak airway pressure was increased, but was reduced within hours while peep was maintained ( fig. ). at hours both peak airway pressures and peep were reduced to baseline values while p/f ratio remained stable. only one patient ( . %) died of disseminated invasive aspergillosis. conclusions: the p l guided olc improved oxygenation and none of the patients required vvecmo. these findings support a ventilation strategy guided by transpulmonary pressures instead of plateau pressures in patients with severe ards. introduction: the mortality benefit conferred by early prone positioning in the treatment of acute respiratory distress syndrome (ards) has been well established. we also know that aprv improves oxygenation, and more recently has been shown to reduce ventilator dependent days and icu length of stay [ , ] . however, controlled ventilation remains the mainstay mode of ventilation used during prone position. literature looking at combined aprv and prone positioning is scarce. we aim to explore and report our institutional experience with respect to feasibility and outcomes in combining aprv and prone positioning, and perform a literature review in this area. methods: we undertook a single-centre retrospective cohort study within a surgical icu of a tertiary hospital in singapore between jan -oct . patients with ards who received combined prone positioning and aprv were reviewed retrospectively. a literature review of patients with ards who received combined intervention was also performed. results: adult patients aged - years old diagnosed with ards received a combination of aprv and prone positioning for a duration of - h ( table ). all the patients tolerated aprv with prone positioning well. our patients saw an improvement of p:f ratio ranging from - upon completion of combination therapy. out of patients were extubated within hours of turning supine, was weaned to tracheostomy mask after days and died while on the ventilator. only case report and randomized clinical trial were found on this topic upon literature review, which corroborated our findings. conclusions: in our experience, aprv is a practical and feasible alternative mode of ventilation that can be employed in the prone position, yielding significant p:f ratio improvements. the synergistic effects on improving oxygenation herald potential, especially in the subset of severe ards patients with refractory hypoxemia, where extracorporeal membrane oxygenation is unsuitable or unavailable. introduction: the recirculation during veno-venous extracorporeal membrane oxygenation (vv ecmo) had been a drawback, which could limit sufficient oxygenation. purpose of this study is to compare the short-term oxygenation in acute respiratory distress syndrome (ards) patients under vv ecmo according to their cannula configurations, especially in the national environment of the absence of newly developed double-lumen, single cannula. introduction: vv-ecmo is most commonly used in severe potentially reversible respiratory failure. this report looks at two patients in whom vv-ecmo was used to facilitate surgical airway stenting. methods: case -a -year-old with recurrent respiratory arrests, on a background of neurofibromatosis type and kyphoscoliosis. he had complex airway pathology, including, airway neurofibromas and granulation tissue, tracheobronchomalacia, severe kyphoscoliosis and a permanent tracheostomy tube. rigid bronchoscopy was performed and following debridement of granulation tissue, a trouser-leg stent was deployed. case -a -year-old with progressive stridor due to recurrence of a malignant melanoma, which was causing mid-lower tracheal compression. three tracheal stents were deployed via a rigid bronchoscope. in both cases, percutaneous bi-femoral vv-ecmo was established prior to general anaesthesia and decannulation took place the following day. results: in these cases, vv-ecmo provided stable extracorporeal gas exchange without conventional tracheal intubation. cardiopulmonary bypass and veno-arterial ecmo have been described in patients at risk of compression of the heart and distal airway [ ] . however, if the major threat is airway collapse, vv-ecmo can provide cardio-respiratory support without the problems associated with arterial cannulation and with lower anticoagulation requirements. introduction: ecco r facilitates the use of low tidal volumes during protective or ultraprotective mechanical ventilation when managing patients with acute respiratory distress syndrome (ards); however, the rate of ecco r required to avoid hypercapnia remains unclear. methods: we determined ecco r requirements to maintain arterial partial pressure of carbon dioxide or co (paco ) at clinically desirable levels in ventilated ards patients using a six-compartment mathematical model of co and oxygen (o ) biochemistry [ ] and whole-body transport [ ] with the addition of an ecco r device for extracorporeal veno-venous removal of co . the model assumes steady state conditions and is comprehensive from both biochemical and physiological perspectives. o consumption and co production rates were assumed proportional to predicted body weight (pbw) and adjusted to achieve pao and paco levels at a tidal volume of . ml/(kg of pbw) as reported in lung safe [ ] . clinically desirable paco levels during mechanical ventilation were targeted at mm hg for a ventilation frequency of . /min as previously reported [ ] . results: model simulated paco levels without and with an ecco r device at various tidal volumes are tabulated in tables and , respectively. table shows a substantial increase in paco at a tidal volume of ml/(kg of pbw) that is more pronounced when further reducing the tidal volume. additional simulations showed that predicted ecco r rates were significantly influenced by ventilation frequency. conclusions: the current mathematical model predicts that ecco r rates that achieve clinically acceptable paco levels at tidal volumes of - ml/(kg of pbw) can likely be achieved with current technologies; achieving such paco levels with ultraprotective tidal volumes of - ml/(kg of pbw) may be challenging. figure a ). pulmonary infections for each subtype of immunosuppression are shown in figure b . conclusions: ards vv-ecmo patients with underlying immunosuppression have higher mortality rates and higher rates of ecmo weaning failure. immunosuppressed patients suffer from a different spectrum of pulmonary infections in comparison to not immunosuppressed patients. introduction: acute asthma attack in children is a life-threatening emergency that requires urgent medical intervention. in the present study, we aim to clarify the effect of non-invasive ventilation (niv) on the heart rate (hr), respiratory rate (rr), and fraction of inspired oxygen (fio ) in children with acute severe asthma (asa) who failed to respond to standard medical treatment; and to evaluate the associated complications and length of stay (los) at the pediatric intensive care unit (picu). methods: this is a retrospective descriptive study of prospectively collected data. it was carried at the picu of a tertiary university hospital, saudi arabia. the study included children ≤ years old with asa admitted to the picu from november to november and required niv. outcome measures include the effect of niv on the hr, rr, fio , and los. the study included children with asa and ( %) of them required niv. of those patients, ( %) were excluded due to incomplete data, and ( %) patients were included in the final analysis. they were ( %) male and ( %) female with a mean age of months and a median pediatric index of mortality (pim ) score of . %. of them, ( %) had moderate asthma scores (≥ - ) and ( %) had severe asthma scores (≥ ). the median duration of niv was hours and the median los in the picu was three days. at hours, only rr showed a significant decrease compared to initiation of niv (p-value < . ) (fig ) ; while hr, rr, and fio were significantly improved at hours from initiation of niv (p-value < . ) (fig ) . conclusions: non-invasive ventilation, in association with standard medical treatment, was associated with clinical improvement in children with asa not responding to standard medical treatment alone. niv was not associated with significant complications or side effects. neurally adjusted ventilatory assist (nava) is a partial support ventilatory mode which triggers and tailors the level of assistance delivered by the ventilator to the electrical activity of the diaphragm. the objective of this study was to compare nava and pressure support ventilation (psv) in patients who were difficult to wean. methods: a total of difficult-to-wean patients who were able to sustained psv in the critical care medicine unit (icu) of the zhongda hospital, southeast university were enrolled in the study (fig ) . patients were classified according to the reason for weaning failure and were randomly assigned to receive nava or psv during weaning ( table ). the primary outcome was the duration of weaning. secondary outcomes included the proportion of successful weaning and patient-ventilator asynchrony. results: there were % ( / ) and % ( / ) patients in the psv and in the nava group never weaned from mechanical ventilation (p = . ). the duration of weaning was significantly shorter in the nava group [ . ( . - . ) days], than in that in the psv group [ . ( . - . ) days] (p = . ). the proportion of patients with successful weaning was % (n= / ) in nava group which was much higher than that in psv group ( %, n= / ) ( table ) . compared with psv, nava improved the rate of successful weaning in patients with single reason ( % vs. %, p = . ) but not in patients with multiple reasons for difficult weaning ( % vs. %, p = . ). nava decreased ineffective efforts and improved the trigger and cycling-off delays when compared with psv. mortality was similar in the two groups (fig ) . in patients who were difficult to wean, nava decreased duration of weaning and increased the probability of successful weaning. nava which improved patient-ventilator asynchrony, is safe, feasible and effective over a prolonged period of time during weaning. conclusions: only mrc score is independently associated with sbt failure and difficult or prolonged weaning. hgs is also associated with these two outcomes related to mv weaning and may serve as a simple tool to identify icuamw. introduction: there is evidence to support that in patients with hypoxemic respiratory failure (ahrf) under non invasive ventilation (niv), high tidal volume (tv) and high respiratory rate (rr) are associated with niv failure and possibly poor prognosis. we postulated that high minute ventilation (mv); or tv x rr; is associated with mortality in ahrf, when niv is initiated. methods: single-center, prospective and observational study. we included consecutives ahrf adults requiring niv. ahrf was defined as acute dyspnea with new pulmonary infiltrates on chest radiography and paco below or equal to mmhg. we registered demographic and clinical parameters (including rr, mv, arterial blood gases, heart rate and blood pressure) at baseline and after hours of first session of niv, apache ii score, diagnosis, need for intubation and icu mortality. we performed a multivariate analysis to assess independent factors associated with mortality and roc . ) and (auc = . ; p = . ), respectively for mortality, future exacerbations and readmissions. the optimal cut-off point for the mwt ratio to predict mortality was . and to predict future exacerbations and readmissions was . . the mwt ratio performed at icu discharge reveals interesting discriminative properties to predict early mortality, future exacerbations and readmissions in ae/copd patients. diffuse alveolar haemorrhage in an intensive care unit -search and you will find m matias , e ribeiro , j baptista , p martins introduction: the incidence of diaphragmatic ruptures after thoracoabdominal traumas is . - % [ ] and up to % diaphragmatic hernias present late [ ] when there is a complication. we report two cases of delayed traumatic diaphragm rupture to highlight the diagnostic difficulties. methods: case (image ) presented left diaphragmatic hernia containing the stomach, spleen, bowel and pancreas. the patient reported a motor vehicle accident dating months. he had thoracoabdominal trauma with several broken ribs on the left side. he then reported occasional pain in his left shoulder and occasional dyspnoea. case (image ) showed right diaphragmatic hernia containing right hemicolon, right hepatic lobe and gallbladder, he reported occasional dyspnoea and recent right chest pain. he had a years car accident in which three ribs broke on the right side. results: almost % of the patients with delayed diaphragmatic rupture presented with complications between and months after trauma, singh [ ] reported a diaphragmatic rupture presenting years after the traumatic event. the physical examination is often not helpful. conclusions: those cases emphasizes on the delayed presentation, patients may be asymptomatic or produce only mild, nonspecific symptoms, such as vague abdominal pain, chest pain or recurrent dyspnoea for months or years. the best tool to guide the clinician toward the appropriate diagnosis is a high index of suspicion whenever there is a history of high velocity trauma, regardless of how remote. factors associated with asynchronies in pressure support ventilation (psv), a bench study introduction: critically ill patients frequently have increased risk of ocular surface disorders (osds) due to poor eyelid closure and reduced tear production due to sedation during mechanical ventilation. we conducted a study to look at the incidence of osds in our icu with the current eye care practices and the impact of a protocolised eye care on the incidence and outcome and to determine the correlation of risk factors with the incidence of osds methods: this study was done in our mixed medical surgical icu. it had a prospective cohort design and was done as before and after study in two phases (phase i and phase ii). in phase i existing eye care practices were continued. in phase ii protocolised eye care was implemented and incidence of osds was noted in both phases. introduction: both fentanyl and morphine are known as opioid analgesics, which blocks the brain from receiving pain signals, the route of administration and the adverse effects affect their use. we compare the efficacy of intranasal fentanyl versus intravenous morphine adults population presenting to an emergency department (ed) with acute post traumatic severe pain. methods: we conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in a tertiary emergency department between october and june . adults with severe post traumatic was included to receive either active intravenous morphine ( mg immediately and then mg every min if persistence of severe pain maximum mg) and intranasal placebo or active intranasal concentrated fentanyl ( μ g /kg maximum μ g) and intravenous placebo. exclusion criteria: significant head injury, allergy to opiates, nasal blockage, or inability to perform pain scoring, pain scores were rated by using a digital scale at , , , and minutes. routine clinical observations and adverse events were recorded. conclusions: iscs were related to k over-use in our bicu. burnt patients are at risk of hepatic injury [ ] , but k related hepatic injury likely occurred. its not clearly understood mechanisms may involve a cumulative dose effect. although involvement of concomitant medications is being investigated, k restriction policy seemed to contain hepatic disorders. introduction: in november , our institution switched from using alfentanil to fentanyl for analgesia and sedation in adult patients receiving ecmo. there is no published evidence comparing the clinical use of alfentanil vs fentanyl for sedation in ecmo patients, although some reported increased fentanyl sequestration into the circuit [ ] . for these reasons, we conducted a retrospective observational study to explore whether there were any significant differences in patient outcome or adjunctive sedation before and after the switch. methods: outcome data and total daily doses of alfentanil or fentanyl as well as adjunctive sedation/analgesia for each patient where obtained from our clinical information system (philips icca®). data was included from ecmo patients who were sedated with alfentanil or fentanyl from / / to / / until ecmo decannulation. patients not requiring either opiate or who were switched between the two during ecmo therapy were excluded. all medicines prescribed for the management of sedation or agitation were included. for each patient an average total daily dose of each drug, was calculated. data was analysed using stata®. results: both groups were found to be statistically equivalent for mode of ecmo, age, apache score and charlson score (p= . ) except for bmi (p= . ). no difference in patient outcomes were found between groups (table ) . patients in the alfentanil group were found to have received significantly higher median average total daily dose of quetiapine and midazolam (table ) . conclusions: no differences in patient outcomes were found between patients sedated with alfentanil compared to fentanyl. we introduction: the european society of intensive care medicine consensus statement recommends that for comatose survivors of cardiac arrest hours without sedation is the minimum acceptable before neurological assessment. they highlighted the need to investigate the pharmacokinetics of opioid drugs in post-cardiac arrest patients, especially those treated with controlled temperature [ ] . methods: following approval by research ethics committee, we measured the blood concentration of fentanyl in post-cardiac arrest patients treated with ttm following cessation of continuous infusion. the fentanyl was discontinued when the patients were rewarmed to a temperature of . degrees celsius and a blood sample taken hours later. the blood was analysed using a commercial elisa kit (neogen corporation). using the total dose of fentanyl administered, the half-life of fentanyl was calculated for each patient. patient physiological data, cyp a and abcb polymorphism and drug history were compared with half-life. results: the median fentanyl concentration at hours was . mcg/l with a very wide range ( . - . mcg/l). the results for calculated half lives are shown in figure . there was no correlation between fentanyl level and bmi, illness severity (saps ll), creatinine clearance, transaminase or lactate level. there was no correlation between co-administration of drugs of metabolised by the cyp a and abcb enzyme systems or genotype. conclusions: there is marked variation in the concentration of fentanyl at hours in patients managed with ttm following cessation of fentanyl infusion. the calculated clearance of fentanyl in some patients is greater than hours and a hour cut off is not safe. introduction: objective of this study was to compare the effects of three analgesic regimens, one opioid and two multimodal ones, on cardiovascular stability and pain intensity in patients undergoing elective surgery under general endotracheal anesthesia during the h postoperative period. methods: sixty elderly patients, asa ii, undergoing elective knee sugary were assigned to receive ) morphine or mg iv q h, depending on body weight, and paracetamol g iv q h (mp group), or multimodal nerve block: ) femoral nerve block, single shot (fnb group) or ) fascia iliaca compartment nerve block single shot (ficnb group). measurement of pain intensity was performed with numerical introduction: opioids are frequently used in the intensive care unit (icu) to relieve pain and facilitate tolerance of life-support technologies. when discontinued abruptly, patients may develop a cluster of symptoms known as opioid-associated iatrogenic withdrawal syndrome (oiws). this phenomenon is poorly described in critically ill adults although it is associated with unfavourable outcomes, such as prolonged icu stay. the objective of this study was to describe the signs and symptoms of oiws in adult icu patients. methods: a prospective observational study was conducted in two tertiary care centres in patients requiring mechanical ventilation and regular opioids for more than hours. after an opioid dose reduction of at least %, patients were assessed daily for signs and symptoms of withdrawal using a standardized form. concomitantly, the presence of oiws was assessed daily by a physician using modified dsm- criteria. all physician evaluations were blinded and performed independently. inter-rater reliability for dsm- evaluations was assessed with the kappa coefficient. results: a total of patients were screened and twenty-nine enrolled. the majority were male ( . %) with a median age of . the median apache ii score was . withdrawal occurred in . % of patient within a median of three days (iqr to days) from opioid weaning. according to investigator assessment, restlessness, agitation, anxiety, hallucinations, insomnia/sleep disturbance, mydriasis and elevated blood pressure were more prevalent in oiws-positive patients. dsm- evaluations identified dysphoric mood, muscle aches, lacrimation/rhinorrhea, pupillary dilation/piloerection/sweating, diarrhea and yawning more frequently in oiws-positive patients. the kappa coefficient showed good agreement ( . ). conclusions: oiws in critically ill adults presents with a large spectrum of signs and symptoms that occur within a median of three days from onset of opioid weaning. further studies are needed to confirm these preliminary findings. withdrawal reactions after discontinuation or rate reduction of fentanyl infusion in ventilated critically ill adults s taesotikul introduction: propofol is a well-known sedative, commonly used in intensive care units (icu s), that on rare occasions has been reported to cause green urine and has also been associated with pink or transient white urine discoloration. it can cause several adverse effects, such as low blood pressure, pain on injection, apnea, hypertriglyceridemia and when administered in high doses it may lead to the "propofol infusion syndrome". methods: we present two examples of interesting urine discolorations observed unexpectedly in our icu in patients under propofol sedation requiring mechanical ventilation. results: dark green urine discoloration as presented in fig. is the result of a phenolic metabolite of propofol that is produced in the liver and is subsequently excreted in the urine, thus changing its color. it is considered a reversible phenomenon that resolves after propofol discontinuation.respectively, pink urine discoloration as presented in fig. can also be the result of propofol infusion. the increase in urine excretion of uric acid caused by propofol, in combination with a low urinary ph can lead to the formation of uric acid crystals and turn the urine pink. discontinuation of propofol and urine alkalization can reverse the phenomenon. conclusions: green or pink urine discoloration due to propofol is generally a benign, reversible condition. its presence should not compel the physician in charge to perform unnecessary testing, although other causes of discoloration should be considered. as far as green urine discoloration is concerned, other factors such as drugs, dyes, certain nutritional supplements or even a pseudomonas urinary tract infection may be at fault. on the other hand, pink urine syndrome due to propofol infusion seems to be even rarer. although its presentation is not alarming, it may well increase the risk of uric acid lithiasis, a fact that the physician in charge should always keep in mind. conclusions: hepatic changes related to propofol are frequently observed and should be systematically monitored to ensure patient safety. fig. (abstract p ) . dark green urine discoloration introduction: clevidipine (clev) and propofol (prop) are lipid-based medications used in the intensive care unit (icu) for hypertension and sedation, respectively. no data exists regarding potential adverse effects of concurrent therapy with this combination. this study aims to evaluate the incidence of hypertriglyceridemia (htg) and pancreatitis in icu patients using concurrent clev and prop. methods: this was a single-center, retrospective chart review in patients utilizing clev and prop concurrently from february to november . patients were included if they were years and older, on clev and prop concurrently for at least hours with no more than hours of interruption at a time, had at least one triglyceride (tg) level during concurrent therapy, and admitted to the medical or surgical icu. the incidence of htg (defined as tg equal to or greater than mg/dl) and pancreatitis (provider assessment based on american college of gastroenterology guidelines) was evaluated. patients with and without htg were compared to identify risk factors for the development of htg. results: of patients screened, patients were included which comprised observations. the incidence of htg was . % with no patients developing pancreatitis. patients with htg had a higher median age compared to without htg ( . vs. ), p= . . in patients with htg the median dose of clev and prop were mg/h and . mcg/kg/min, respectively, which was higher but not statistically significant when compared to patients without htg. cumulative lipid load (g/kg/d) was non-significantly higher in patients with htg ( . vs. . ), p= . . conclusions: the incidence of htg was comparable to what is cited in literature for prop alone. patients with htg were older, had higher median clev and prop doses, and a larger cumulative lipid load compared to patients without htg. introduction: the society of critical care medicine guidelines for pain, agitation and delirium suggested use of nonbenzodiazepine sedatives like dexmedetomidine which is associated with a reduced duration of mechanical ventilation, shorter length of hospital stay and a lower incidence of delirium [ ] . enteral clonidine represents a potentially less costly alternative for agitated patients with prolonged dexmedetomidine infusion. limited literature exists examining this transition for management of agitation [ ] . methods: the critical care management initiated an action plan on the transition of patients with prolonged dexmedetomidine infusion to oral clonidine. a protocol was prepared with clinical pharmacist's assistance. risk factors were assessed and inclusion criteria were applied as per protocol. dexmedetomidine infusion rate was reduced gradually with oral clonidine administration in selected patients. other rescue managements were implemented as per protocol. oral clonidine was then tapered down by reducing frequency of administration over few days. results: post intervention data in showed significant decrease of dispensed doses and cost of the injections compared to . the annual cost saving was % equating to , usd (table , figure ). conclusions: transitioning to clonidine may be safe and less costly method of managing agitated critically ill patients on prolonged dexmedetomidine infusion. more studies are needed to evaluate the efficacy and safety of this practice. incidence of dexmedetomidine associated fever at a level trauma center na beaupre, jt jancik hennepin county medical center, pharmacy department, minneapolis, united states critical care , (suppl ):p introduction: we evaluated the incidence of dexmedetomidine associated fever (daf) in a level trauma center's medical intensive care unit (micu). hypotension and bradycardia are the most commonly reported adverse effects associated with dexmedetomidine (dex) infusion. case reports suggest dex can cause fevers and the clinical trials that led to the approval of dex demonstrated fever rate to be - % [ ] . methods: this was a single-center, retrospective chart review of patients admitted to the micu at hennepin county medical center between march and july of that were started on a dex infusion. patients were included if they were years and older, on a dex infusion for at least hours, and had temperature data available. fever was defined as > . c and other causes of fever including infections, medications, withdrawal, recent surgery, thromboembolic disease, thyroid disorders and seizures were excluded from analysis. results: of the patients screened, were included. the mean age was years and . % were males. of all the patients included, the mean change in temperature after initiation of dex infusion was + . c from baseline. the mean initial dose was . mcg/kg/hr. four of patients ( . %) had a daf. of those that had a daf, the median initial dose was . mcg/kg/hr; the median time of infusion was . hours; and the median cumulative dose was . mcg/kg/hr. the median time to fever after initiation of dex was hours, with a range of to hours. the median time to fever cessation after discontinuation of dex was hours. conclusions: in our population, the incidence of dexmedetomidine associated fever was relatively rare at . % and similar to current literature rates. the results obtained showed a statistically significant fact that fewer points on the test, from to points, received older patients who underwent an urgent surgical procedure, over years of age, of which % . also statistically significant data were obtained that patients who used a higher amount of sedatives during emergency surgery, % had a worse test result than under points due to increased preoperative anxiety. the older population is more susceptible to postoperative delirium, especially in emergency surgery situations, which they carry, unpreparedness for surgery, increased use of medication for fig. (abstract p ) . flowchart of enrolled patients calm, unpredictability of the duration of surgery, and therefore anesthesia as well the use of anticholinergics, which is sometimes impossible to avoid in operative procedures such as gall bladder surgery. the results of the study suggest that in cases of emergency surgery, the use of protocols for postoperative delirium should be planned regularly to prevent or at least mitigate the clinical picture of delirium that can lead to complications postoperatively. introduction: delirium is a serious and often underestimated condition with implications for morbidity, mortality and healthcare costs. as it presents in a wide range of settings from admission to discharge, early prediction and risk assessment are essential. e-pre-deliric is a delirium prediction score which has been validated in itu patients but not in other populations, and we conducted a quality improvement project using this score to assess its utility in other settings. methods: data was gathered from three patient categories: those undergoing elective surgery (es), admissions to the emergency observation unit (eou) in the a&e, and patients with fractured neck of femur (nof). clinical notes were reviewed to collect data to calculate e-pre-deliric score at admission, along with a number of other clinical variables including incidence of delirium, and statistical analysis performed. results: a total of patients were included, with in the es group, in the eou group, and in the nof group respectively, with an overall average e-pre-deliric score of . %. es had a . % average e-pre-deliric score, a mean age of and no cases of delirium. the eou group had an average age of , a . % average e-pre-deliric score and no incidence of delirium. the nof group had a mean age of and an average e-pre-deliric score calculated on admission of . %. this was the only group in which patients developed delirium. a % cut off was demonstrated to be the most accurate to predict delirium in this population with a sensitivity of . and a specificity of . . conclusions: despite the limitation of a small sample size, this project has shown that e-pre-deliric score could be a useful tool to predict patients at high risk of delirium in a non-itu setting, with a % cut off in hip fracture patients. further investigation should be conducted into the potential use of e-pre-deliric in non-itu patients. comparison of long-term mortality between patients with and without delirium during admission in medical intensive care units in a university hospital n kongpolprom king chulalongkorn memorial hospital, pulmonary unit, bangkok, thailand critical care , (suppl ):p that delirium is linked with preoperatory comorbidities. the complexity of surgery has a big influence on the development of delirium, especially in the cases of aortic dissection. delirium was associated with intraoperatory blood transfusions. finally, our data point to a bridge between postoperatory electrolytic disturbances, as well as inflammation as factors potentially triggering delirium onset. introduction: we did a retrospective case note study of mortality due to sepsis of our unit over three months as observational study in which we noted the causes of deaths, origin of sepsis, organism, patient characteristics and icnarc physiology scores and icnarc h model predicted risk of acute hospital mortality percentage. methods: icnarc data base was used to gather the data and coding was used to identify the patients with sepsis for three months. patients mortality attributed to sepsis were identified from mortality list.causes of death were noted from patients notes and death certificates.cyber lab was used to access the data and case note were ordered for review.patients characteristics were noted including dnacpr orders and treatment withdrawal orders. scores (apache scores, icnarc physiology scores, icnarc h predicted risk models of acute hospital mortality percentage) were noted. results: mortality percentage was found to be % as per codig which was reduced to % as % deaths were attributed to other causes. % patient had dnacpr in first hrs. average length of stay was . days with median of . days.median age was yrs in surviving age group and years in other. icnarc physiology score with predicted risk of . %. commonest cause was found pneumonia % followed by urine tract infection. % patients were with no source identification. conclusions: conclusion was made that we do need to improve the coding as significant percentage was mentioned as sepsis as cause of death where clinicians differed. pneumonia was found to be the commonest killer in critical care followed by urine tract infection. it was pointed to be useful to carry out further audit targeting pneumonia .review of icnarc case mix program, development of icnarc physiology score, which provides excellent local use with downside of lacking international comparison was done also. introduction: hospitals vary widely in the quality of care they provide for septic patients. since many septic patients present to their nearest hospital, local variations in care quality may lead to geographic disparities in access to optimal sepsis care. we sought to better understand geographic access to high quality sepsis care, taking advantage of publicly reported data on sepsis management and outcomes in a large us state. methods: we performed a cross-sectional analysis of geographic access to high quality sepsis care, taking advantage of a new york state initiative that mandates public reporting of sepsis quality data to the state government. we linked these data to the locations of hospitals in new york state from the us centers for medicare and medicaid services and population data from the us census bureau for . we defined hospital sepsis performance using self-reported risk-adjusted mortality rates (ramr) and defined high-performing hospitals as those with a ramr < %, which represents the lower end of short-term mortality typically observed in sepsis. we used arcgis to generate drive-time estimates and assess population access to high performing acute care hospitals for sepsis care. results: hospitals publicly reported treating , cases of sepsis from a population of , , persons. overall access to an acute care hospital was excellent at the -minute drive threshold ( . %), good at the -minute threshold ( . %), and marginal at the -minute threshold ( . %). we classified hospitals ( . %) as high-performing based on a ramr < %. high-performing hospitals reported , ( . %) of the total sepsis cases. high-performing hospitals were geographically dispersed across the state, although population access diminished substantially with increasing drive times ( . % at -minutes, . % at -minutes, and . % at minutes; figure ). conclusions: one in six people do not have timely access to a high performing hospital for sepsis care using a -minute threshold. [ ] . this poses a significant safety risk. a previous study found that the implementation of a multidisciplinary medication safety group in intensive care increased reporting of errors and near misses [ ] . the purpose of our work was to set up a multidisciplinary group to provide a forum to review and improve medication safety at all stages of the process. here we discuss some of the initiatives and outcomes implemented in the last months. methods: ccmsg was formed in , under the leadership of the critical care pharmacy team, with representation from medical and nursing disciplines. the group meet fortnightly to analyse trends in medication errors, implement changes to local practice and review outcomes to improve patient safety. the cohesive, multidisciplinary nature of the group allows medication safety initiatives to be delivered in the most effective way. results: on average, ccmsg reviewed medication errors per month. the most common high risk drug classes involved are seen in table . medication safety initiatives implemented were based on these trends and included writing guidelines and policies, bedside education, teaching and training, informatics optimisation and operational changes. examples are seen in table . conclusions: initiation of a ccmsg provides a cohesive approach to facilitate the implementation of targeted safety initiatives, which are proven to reduce some of the most common medication errors in critical care. in addition, these often result in optimisation of operational and financial inefficiencies. introduction: cis/hospital electronic medical records downtime can cause major disruptions to workflow, patient care, key communication and information continuity [ ] . here we describe the consequences of deploying a business continuity plan (bcp) designed to support a critical care clinical informatics system (cis) failure, during an -hour unplanned downtime in a large central london icu. the institutional bcp was developed through an iterative process based on cis provider recommendations and internal workflow knowledge. it consisted of a web offline chart (woc) that is accessible at every computer connected to the network (in the event of a cis server fault), and via hard copy from designated back up computers connected to a printer (in the event of whole network loss). operational and clinical consequences were recorded during informal and formal debrief of the informatics team. the decision making around´drop-to-paper´was reviewed. -the bcp permitted´drop-to-paper´, service continuity and controlled uptime -patchy network loss and lack of a general institutional bcp delayed initial system failure diagnosis (network vs primary server); reduced reliability of´read-only´data and delayedd rop-to-paper-day-to-night handover during downtime led to loss ofḿ emory´of key patient data/events, and should have accelerated decision to´drop-to-paper-transfer of prescriptions was time consuming, distracting (occupied cis team) and prone to error conclusions: previous end-to-end testing of the bcp had not identified many of the observations and recommendations that came from the analysis of an actual period of unplanned downtime. we recommend sharing of similar experiences and scheduled high-fidelity simulated downtime in other institutions to replicate real world conditions, particularly in a critical care setting. . ) were predictors of icu transfer. we developed a simple score to predicting icu transfer from previous variables and performed analysis of auc of roc, which was compared to that of apa-che ii. the result showed the auc of roc of a new score was slightly higher than the apache ii, namely . vs. . respectively. conclusions: the immunocompromised patients take two times higher risk than the immunocompetent ones regarding icu transfer. the other risk factors are lower gcs, lower sbp, and higher rr. a newly developed score may be a promising tool for predicting and triaging site of care in patients who require imcu admission. introduction: this research aims to explore the role of situation awareness in the decision-making of patient discharge from the intensive care unit (icu). the discharge of these patients is a complex and, moreover, a challenging transition of care. readmissions are undesirable given the association with a more extended hospital stay and a possible chance of higher mortality. little is known on how the decision-making process takes place and accordingly, the role of situation awareness of patient discharge from the icu. in order to improve the quality of care of patient discharge from the icu, further research is necessary. methods: this research concerns a qualitative study in which various health care providers, working in an icu adults of a large teaching hospital, were interviewed. through purposive sampling, six nurses, two physician assistants, two intensivists and a physiotherapist were included. on the obtained data a thematic analysis was applied, based on the principles of the grounded theory. results: the discharge decision of icu patients seems mainly based on the team´s situation awareness, with the initiating role of the intensivist and the guiding role of the nurse. furthermore, there is an additional role for the physician-assistant and a consultative role for physiotherapy in the process of the decisionmaking. worries of patients and family seem not to affect the decision-making directly. in the decision-making process, the well-being of the patients and the possibility to provide the most suitable and best possible care were central. organizational factors, such as an urgent demand for icu beds do count but seem not to push the decision to transfer patients from the icu to the regular hospital ward. conclusions: the decision to dismiss icu patients is a complex process with different disciplines and a variety of factors involved. obtained knowledge and insights into the role of situation awareness provide starting points for improving the quality of the discharge process of icu patients. conclusions: despite the fact that older people was more severe illnes, and similar frequency of respiratory failure, the use of mechanical ventilation, the use of central venous catheter and arterial catheter was less frequent. the addition of a simulation fellow within the intensive care team and introduction of in situ simulation n bhalla, d hepburn, g phillips royal gwent hospital, intensive care unit, newport, united kingdom critical care , (suppl ):p introduction: traditionally, simulation based medical education has been carried out in off site simulation centres, however, we trialled the addition of a simulation fellow, within our intensive care team, to run an in situ simulation (iss) program on our intensive care unit over a month period. methods: our multi-disciplinary iss program, led by a simulation fellow, incorporated participants, observers and facilitators including doctors (junior trainees up to consultants of varying medical specialties), nursing staff, healthcare support workers, operating department practitioners, physiotherapists and medical students. we ran simulated emergency scenarios and technical skills sessions. with every scenario, we collected data on participant and observer feedback using the world health organisation participant feedback form and conducted a satisfaction survey at the end of our trial period. results: our results, highlighted in table , show participants found iss led by a simulation fellow realistic, well structured and organised. it was useful for testing and understanding our response systems, fig. (abstract p ) . patient journey of group : those patients discharged home days after step down from critical care identifying strengths and gaps and establishing individual roles/functions within emergencies; overall leaving us feeling better prepared for critical care emergencies. from our satisfaction survey, % of participants found the simulation fellow a useful addition to the intensive care team and expressed the need for more in situ simulation. conclusions: the addition of a simulation fellow allowed for numerous disciplines within the critical care team to be involved in challenging emergency scenarios (fig , ) , with the additional realism of being on the intensive care unit playing the role they would in real life; as well as having opportunity for spontaneous discussion and learning. from this they reported great benefit and satisfaction. following our initial success with this program, we plan to have a simulation fellow as an ongoing role within our critical care team. impact of multidisciplinary team in readmission in a brazilian cardiac intensive care unit c bosso , p introduction: the aim of this study is to determine the importance of the multidisciplinary team at readmission rates in a cardiac intensive care unit (cicu). methods: retrospective study with analysis of patients in a cicu of a medium size brazilian hospital. the years of and represent the reduced team (physician, nurse and physiotherapist) and and the complete multidisciplinary team (additional presence of phonoaudiologist, psychologist, pharmacist, dentist and nutritional professional). the risk of mortality was determined by saps score. in order to compare the teams, it was utilized odd ratio of a logistical sample to the discrete data, and t-student test to the continuous data. the data analysis was executed from the software rstudio ( . . ), and the significance level adopted was %. results: the number of patients was of n= ( from the reduced team and from the multidisciplinary team). the age, sex and bmi didn`t present significant difference between groups. the average age of the sample was ± years old (p= . ). the male sex represented % (p= . ), and the bmi was around . ± . (p= . ). the main diagnoses were similar in both groups -coronary angiography with stent ( %), unstable angina and non st elevation myocardial infarction ( %). table shows the average, standard deviation, p-value to t-student test to saps score and lengh of stay (days), according to both reduced and multidisciplinary teams. table exposes the mortality rate and readmission for both teams. the figure shows the odds ratio and its ic % to the comparison of the mortality, readmission, hours readmission and hours readmission rates between the teams. conclusions: the multidisciplinary team performance reduced the number of hospital readmissions in and hours in a cicu. methods: during the initial audit hours' worth of waste from one itu bed was manually divided into the categories above. results: based on these figures it was estimated that a saving of £ per year would be made (£ . per bed space) over the course of a year should domestic waste bins be placed across the bed icu/hdu. a business case was made, and every bay had a domestic waste bin installed with poster signs for explanation.the reaudit in which all domestic waste across the unit was weighed produced an even greater figure of a saving of £ per bed space (£ ) per year. conclusions: introducing a domestic waste bin may save approximately £ per year per bed. in a typical itu such as lewisham ( itu beds/ hdu beds) that may mean a saving of £ per year (with % capacity). there are also environmental benefits, burning of plastics releases harmful dioxins. the authors wish to make intensive care units and indeed all areas of the hospital aware of the cost and environmental impact associated with disposing of waste in incorrect categories. we hope that our quality improvement project demonstrates how easily money may be saved and environmental footprint reduced. association between resilience and level of experience in intensive care doctors in india j gopaldas, a siyal manipal hospital, bangalore, critical care medicine, bangalore, india critical care , (suppl ):p introduction: attrition of doctors in intensive care unit (icu) is one of the highest amongst all medical specialities globally, and is strongly associated with stress and burn out syndrome (bos). factors that contribute to bos are low pre-morbid resilience and low level of icu experience. studies from india have shown high levels of stress in intensive care doctors (> %), but there are no published studies measuring pre-morbid resilience and risk of burnout in relation to years of experience amongst icu doctors. our main aim was to measure cross sectional resilience levels in icu doctors compared between those with less than years of experience to those with years or more. a secondary aim was to assess the impact of other factors that may contribute to low scores. methods: an anonymised survey was conducted involving doctors in icus across different states in india, using the connor-davidson resilience scale (cd-risc ), which is validated in indian population. results: a statistically significant correlation was found between low levels of resilience in icu doctors with under years of experience . ) , and the significance level adopted was %. a logistic regression model was used to test the difference between the mortality and readmission rates in < and ≥ groups, which enabled the calculation of odds ratios. chi-square test was used to evaluate categorical variables and t-student test to some quantitative variables. the roc curve was constructed to verify the sensitivity of prediction of mortality through different saps scores. results: among the < and ≥ groups, respectively % and % was male (p = . ). mean weight of the> years was ± kg and < years was ± (p < . ). odds values indicated a significant difference only for the mortality rate, which was more than double among ≥ . readmissions in any time, h and h as well the mortality is shown in table and odds in figure . there was a significant difference in saps points between groups ( table ). the ≥ group presented an average of points higher on the severity scale when compared with those in the < group. there was no significant difference in lengh of stay. the highest amount provided by saps scores was % and a specificity of % for hospital mortality not group < years. in ≥ group the highest sensitivity was % and the specificity was %. roc curve for saps is shown in figure . conclusions: the extremely elderly patients of a cicu is more severe, with higher mortality and have the same lengh of stay and readmission rates. introduction: the purpose was to assess the prevalence and impact of non-urgent interruptions (nui) within critical care (cc).a root cause analysis of a never event in our cc discussed nui as a contributory factor, paralleled by learning from serious incidents.the negative impact of nui is well evidenced, resulting in delayed task completion, increased stress, and affecting patient safety. methods: any nui during a consultant ward round (cwr) or invasive procedure (ip), not relating directly to the current clinical episode, was included. qualitative data was collected by a survey, assessing the cc multidisciplinary teams(mdt) perception of nui. results: one third of reviews during the cwr, and %of ips, had a nui. adverse effects included prescription omissions, delayed cwr, near-miss with a cvc, and failed picc insertion. overall, % of staff considered nui a problem; % had experienced nui that led to distraction in train of thought. % felt that nui had led to an error: % of doctors, versus % of nurses. % overall felt nui contributed to stress at work. reasons for interruptions included: feeling overloaded, needing to resolve concerns before forgetting/being distracted, unable to prioritise, and to shift responsibility.lack of leadership or clinical supervision providing a point of contact for problems during shifts was mentioned as contributory. senior staff raised that whilst attempts have been made to level hierarchy, allowing a voice for all to express concerns contributes to interruptions. potential solutions included awareness on impact of nui, jobs book,´sterile cockpitd uring ips, and increased clinical supervision during shifts. conclusions: we have demonstrated the prevalence and consequences of nui within cc is significant.the impact on staff is significant, both for contribution to errors and also the negative impact on stress in the workplace. identified potential solution will be implemented. the impact of an education package on the knowledge, skills and self-rated confidence of medical and nursing staff managing airway & tracheostomy/laryngectomy emergencies in critical care l o´connor , k rimmer , c welsh methods: the factors affecting the delivery of intensive care was elucidated by a comprehensive review of the intensive care literature. a further understanding of intensive care delivery in south africa was obtained by "making sense of the mess" with eight workshops and interviews using a systems approach. systemic intervention served as the meta-methodology and methods and techniques from interactive planning, critical systems heuristics, soft systems methodology and the viable system model were employed. results: making sense of the mess emphasised the complexity of intensive care delivery, on both a situational and a cognitive level. it became clear that a single methodology would not suffice, but that a pluralist methodology was required to guide improvement in intensive care delivery. based on this understanding, nine principles were formulated to guide the development of a framework. systemic intervention was again used as the meta-methodology. interactive planning was identified as the key methodology, incorporating methods and techniques used in the making sense of the mess phase to build a systemic framework for the improvement of intensive care delivery. embedded in the proposed framework are matters relating to systemicity, complexity, flexibility, empowerment, and transformation of intensive care delivery. the proposed framework allows for multiple-perspectives, including that of marginalised stakeholders, the mitigation of multivested interests and power relationships (fig ) . it is both flexible and adaptable to promote learning about the complex problems of intensive care delivery and it accommodates the strengths of various relevant approaches to complex problem solving. conclusions: the proposed framework aims to facilitate sustainable improvement of intensive care delivery and to ensure the "just-use" of resources to foster distributive justice. the perioperative management of adult renal transplantation across the united kingdom: a survey of practice c morkane , j fabes , n banga , p berry , c kirwan introduction: there is a limited evidence base to guide perioperative management of patients undergoing renal transplantation and no national consensus in the uk. we developed an electronic survey to provide an overview of uk-wide renal transplant perioperative practice and determine the need for future guidelines on patient management. methods: a -question survey was developed to encompass the entire renal transplant perioperative pathway with input from clinicians with expertise from renal transplant surgery, anaesthesia, nephrology and intensive care. the survey was sent to lead renal anaesthetists at each of the transplant centres across the uk. results: twenty-two centres ( %) returned complete responses. there was limited evidence of guideline-based approaches to preoperative work-up, with marked variety in modality of preoperative cardiorespiratory function testing performed. questions regarding intraoperative fluid management (fig ) , blood pressure targets and vasopressor administration (fig ) identified a broad range of practice. of note, the routine use of goal-directed fluid therapy based on cardiac-output estimation was reported in six ( %) centres whilst nine centres ( %) continue to target a specific central venous pressure (cvp) intra-operatively. a dedicated renal ward was the most common postoperative destination for renal transplant recipients ( % of centres), whilst a renal or transplant-specific hdu provided postoperative care in ( %) centres. the need for care in an icu setting was decided on a case-by-case basis. conclusions: this questionnaire highlighted a high degree of heterogeneity in current uk practice as regards the perioperative management of renal transplant recipients. development of evidence-based national consensus guidelines to standardise the perioperative care of these patients is recommended. fig. (abstract p ) . framework for the improvement of intensive care delivery introduction: postoperative care of high risk patients in the icu used to be considered the gold standard of care in terms of reducing perioperative mortality [ ] . new evidence comes to question this practice [ ] . the primary objective of our study was to detect any benefit of postoperative icu care after elective surgery in terms of patient's outcome, length of hospital stay, complications and cost. methods: a -month retrospective analysis of high perioperative risk patients who were about to be subjected into an elective operation were included into the study. subsequently they were allocated into two groups. group i patients were those admitted into the icu for postoperative care while those admitted into the standard ward consisted group ii. demographic data, length of hospital stay, outcome, need of mechanical ventilation, complications and total cost were recorded. results: a total of patients were recorded, in each group. there was no statistical difference regarding the demographic data between the two study groups. seven patients died before hospital discharge ( in group i and in group ii, p> . ). there was no impact of icu admission on length of hospital stay (p= . ) which is primarily affected by the need of mechanical ventilation (p= . ) and reoperation (p< . ). the total cost and the postoperative cost of hospital care did not statistically differ among study groups. conclusions: according to our study the need of postoperative care of high risk patients in the icu is rather questionable in terms of perioperative mortality, length of hospital stay and cost of care. introduction: tivap is a preferred vascular access device for patients with solid tumors and radiological-guided insertion is a standard of care. however, many hospitals have no access to interventional radiology service. our study aimed to determine whether it is safe to place tivaps in icu for immediate administration of chemotherapy. methods: we analysed prospectively maintained database of our department and collected data for adult pts with tivaps implanted between / and / . the median age was (range - ) years, % were women. all procedures were performed by trained physicians with experience in ultrasound (us). puncture technique was used and tip location was controlled with electrocardiographic (ecg) and us with subsequent chest x-ray confirmation. pts were followed up for at least days after the procedure for complications, functioning of tivap and surgical wound healing. results: all tivaps were successfully implanted in pts. infraclavicular route was used in cases ( . %). difficulties with indwelling guide wire were observed in ( . %) pts but did not precluded implantation. placement complications included pneumothorax (n = ), catheter malposition (n = ) and artery bleeding (n = ). these complications required additional therapy but were managed successfully and resolved without consequences. in the rest cases internal jugular vein (jv) was used. complications were not observed. ecg and us navigation provided optimal tip location control in these situations. surgical wound healed after - days and chemotherapy initiation did not affect healing. all tivaps had adequate functioning days after placement. conclusions: it is feasible to implant tivaps in icu. these devices can be used on the implantation day without jeopardizing patient safety. jv catheterization seems to be optimal approach and us navigation and ecg are sufficient methods for placement control. introduction: there is increasing use of clinical information systems to improve patient safety and quality of care in critical care. with all these systems, a rigorous business continuity access (bca) plan needs to be in place so patient safety is not compromised [ ] and ensure continuity of care. here we evaluate the types of medication errors that occurred during a period of unscheduled downtime; potential contributory factors [ ] and the number of errors involving critical medicines [ ] were analysed. methods: during the unscheduled downtime, all prescribing and administration of medicines were transferred to a paper based system using the patients' web offline chart (woc -philips healthcare). pharmacists at the time double checked the paper charts that were transcribed, to mitigate errors but this was not consistent due to the timing of the event. we retrospectively compared the paper drug charts against the electronic prescriptions and noted all errors for patients. results: in total medication errors were identified & allergy omission ( table ) . pharmacists double checked % of the paper charts. conclusions: our data highlights the risks associated with unscheduled electronic patient management system downtime and the heterogeneity of the types of errors & potential contributory factors. it underscores the need for robust local bca plan implementation, critical review of the woc document and regular staff training around potential unscheduled system downtime. introduction: the transfer of patient care (toc) between the intensive care unit (icu) and hospital ward is associated with a high risk of medical errors [ ] .according to uk national data between - % of patients have an error or unintentional medication change made when moving between care settings [ ] . currently different prescribing systems without interoperability are used between icu areas & ward settings in our institution, resulting in medications needing to be re-prescribed on transfer. we aimed to evaluate the time delay in medication re-prescribing, number of unintentional omissions of drug doses and reasons, as well as percentage of critical medicines [ ] omitted in the first h following discharge. methods: over a month period, discharged patients ( % of all discharges) from two icu units were included. the icu discharge letter which contained the medication list on transfer was compared against the ward based electronic drug chart to identify all unintentional omitted medication doses during the first hours. the starting time point was when the patient physically left icu. results: / ( %) of patients had their medication prescribed more than hours post discharge. there were a total of / , ( %) unintentional omitted doses (table ) . of these / ( %) were considered critical medicines ( table ) . conclusions: this data confirms the risk associated with toc especially around medicines. the need of interoperable electronic prescribing systems is one solution and could improve patient safety by streamlining the process. introduction: staff perceptions of safety may contribute to workforce stress and be organisationally important [ ] . this study explored the feasibility of capturing perceptions of safety with a bedside professional reported (bpr) shift safety score, and explored relationships between bpr and measures of staffing and workload. methods: uk health research authority approval was obtained (id ). data were collected for consecutive days at imperial college healthcare trust ( general critical care beds on sites).the bpr asked all icu staff to rate each shift as "safe, unsafe, or very unsafe". responses were described and correlated with data on organisational staffing (care hours per patient day chppd) and nursing intensity (total number of organs in failure/ total number of nurses). results: a total of bpr scores were recorded (response rate %). we noted heterogenous responses between sites and days, and within shifts, only % of shifts were unanimously rated. whilst % of shifts were rated by staff as "unsafe" or "very unsafe", organisational metrics recorded only % as 'unsafe'. we did not find a correlation between measures of staffing (chppd) and perceptions of safety ( figure ). preliminary analyses suggest that staff perceptions of safety are not well correlated with nursing intensity (figure ), although these numbers commonly inform staffing metrics. conclusions: completing the bpr tool was feasible and acceptable to staff. responses showed variations in perceptions of safety and a gap between organisational metrics and individual perceptions. introduction: delivery of intensive care (icu) is complex because of multiple stakeholders with varied perspectives and conflicting goals that interact and are interdependent. to inform the development of a framework for the improvement of icu delivery in south africa, it was essential to first understand icu delivery or "make sense of the mess". a systemic approach such as systems thinking is required to holistically explore and understand the complexity of icu. no methodology is perfect and methodological pluralism as proposed by systemic intervention, a systems thinking approach, was used for a more flexible and responsive intervention. the methods used was the making sense of the mess phase of interactive planning, stakeholder analysis as describe by critical systems heuristics, rich pictures from soft systems thinking and viable systems model diagnosis. making sense of the mess was done in phases: first the mess was formulated with rich pictures generated in workshops and interviews. the discussions of the rich pictures by the respective stakeholders were transcribed and analysed using braun and clark's thematic analysis. secondly, based on the data generated from phase a diagnosis of the viability of the icu system was made. results: the data from the phases were very rich and complex and themes emerged (figure ). these themes were interdependent and resulted in disorganised icu delivery with limited opportunities for learning to improve icu delivery with dichotomies that existed at various levels of icu. it was a problem to present the complex data in the traditional linear manner due to the interdependence of the themes. the analysis is presented as stories, a known approach in the complexity discipline, where the themes of the analyses are portrayed. the making-sense-of-the-mess phase confirmed the complexity of icu delivery, at both a situational and a cognitive level and with this understanding a framework for the improvement of icu delivery could be developed. introduction: improving prescribing practice involves changing prescriber behaviour. education is assumed to change behaviour but other approaches may be more effective (figure ) [ ] . changes to the presentation of information and the configuration of choices have potential to rectify common prescribing errors through subtle 'nudges' [ ] . the implementation of clinical information systems (cis), including electronic prescribing, provides an opportunity to deploy strategies such as standard orders, dose limits, and product level prescribing. with an infinite number of configuration options available, clinical leaders need to know which interventions are most effective. we evaluated several of these strategies in a before and after observation study methods: interventions, utilising cis nudges, were chosen to improve four areas of prescribing practice in a tertiary critical care unit using methods matched to the top levels of the hierarchy. data were collected for months before and after interventions to map changes in compliance with a pre-defined standard except for the standardisation intervention where months' data were collected due to low prescription numbers. no education on changes was given during the baseline data collection so any change in performance after the go-live date is entirely attributable to the intervention. results: the change in performance for each level ranks the intervention levels in the order (highest first) forced function, automation and standardisation ( table ). the use of point of prescribing reminders was not associated with a significant difference in performance. conclusions: the effectiveness of intervention levels seen in practice is consistent with that of the model. further studies could be undertaken to strengthen these conclusions but in the meantime the approach to changing practice using cis nudges should focus on standardisation or above. introduction: intensive care unit (icu) sound pressure levels (spl) are persistently above world health organisation recommendations for clinical areas [ ] . this may impact patient recovery. standard spl monitoring records single values for each h period (laeq ). we hypothesise this reporting rate is unsuitable for icu. methods: we measured spl october -may , logging frequency (hz), spl (db), and loudness (perception of sound) every second [ ] . the resulting dataset was of a size that conventional statistics programs would require computational resources not easily obtainable on standard university commodity hardware. we processed the full dataset without sampling by using distributed task dispatching, parallelism and scheduling of a cluster computing framework (apache spark). we created a system consisting of a single workstation ( cores; gb ram) running ubuntu . lts, oracle java . , apache spark . , scala . , r core . , r studio . and sparklyr . . . we utilised the sparklyr library in r studio to run arbitrary r code using the dplyr library. we analysed aggregate data in r core & used ggplot (v ) to create visuals. results: we achieved more complex analysis than standard spl reporting with relatively modest computing resources. specifically we identified lower spl peaks in the early hours & loudness levels considerably higher than parallel spl. conclusions: simple laeq do not facilitate reflection on practice thus impetus for change is limited. loudness data highlight the patient experience of spl in the icu is more intrusive than laeq indicates due to high sensitivity to sounds~ - khz, a common frequency range for alarms. higher fidelity increases understanding of spl which can lead to targeted interventions to reduce patient disturbance. introduction: survivors of critical illness face significant long term impairments in mental and physical function. early mobilisation (em) in the intensive care unit has been suggested to improve functional outcomes and reduce delirium in the icu. we hypothesized that implementing a protocol for em in the icu would improve mobilisation rates while remaining safe. methods: design: prospective non-blinded observational cohort study, based on a quality improvement project. data was collected conclusions: only of variables in boyd criteria were significant associated with morbidity or mortality. the physiologic score and operative score were significant higher in the patient on mortality and morbidity after sicu admission. effects of structural hospital characteristics on risk-adjusted hospital mortality in patients with severe sepsisanalysis of german national administrative data d schwarzkopf introduction: the quick sequential organ failure assessment (qsofa) score is a simple tool used to identify severe patients with infection. as this score is calculated from three variables that can be measured at the scene of trauma-systolic blood pressure, respiratory rate and consciousness-the prehospital qsofa score may also be a good predictor of mortality in trauma patients. so we evaluated the discriminative ability of the prehospital qsofa score in patients with trauma for in-hospital mortality. methods: this is a retrospective multicenter study using the data from nationwide trauma registry in japan. we included patients with trauma aged ≥ years old transferred to hospitals from scene. primary outcome is in-hospital mortality. results: the mean age was . ± . years old and patients ( %) were male. in-hospital mortality occurred in patients ( %). in-hospital mortality in each qsofa score was / ( . %), / ( %), / ( %) and / ( %) in qsofa score , , and , respectively (p< . for trend). area under receiver operating characteristics curve (auroc) of the aqsofa score for inhospital mortality was . ( % confidence interval . - . ). if we use the cutoff ≥ , sensitivity and specificity of the qsofa score were . and . . conclusions: in patients with trauma, the prehospital qsofa score was strongly associated with in-hospital mortality. we can identify patients with very low risk of death by using the cutoff ≥ of the prehospital qsofa score. introduction: only one prospective study is available of the validation of the diagnostic and prognostic role of qsofa (quick sofa score) in the emergency department (ed). a prospective study was conducted in greek eds. methods: the prompt study (clinicaltrials.gov nct ) run in the ed of six hospitals in greece among patients with suspected infection and presence of at least one of fever, hypothermia, tachycardia, tachypnea and chills. clinical data were collected and the -day outcome was recorded. sepsis was defined by the sepsis- criteria. results: the sensitivity and the specificity of at least signs of qsofa for the diagnosis of sepsis was . % and . % respectively and for the prognosis of -day mortality . % and . % respectively. the odds ratio for -day mortality when qsofa was equal to or more than was . among patients with charlson's comorbidity index (cci) equal to or less than ; this was . among patients with cci more than (p: . between the two ors by the breslow-day's test; p: . by the tarone's test). conclusions: data validated the sensitivity of qsofa for the diagnosis of sepsis. cci was an independent predictor of severity. qsofa could better predict unfavorable outcome among patients with low cci. comparative accuracy between two sepsis severity scores in predicting hospital mortality among sepsis patients admitted to intensive care unit n sathaporn, b khwannimit prince of songkla university, internal medicine, hat yai, thailand critical care , (suppl ):p introduction: recently, the new york sepsis severity score (nysss) was developed to predict hospital mortality in sepsis patients. the aim of this study was to compare the accuracy of nysss with the sepsis severity score (sss) and other standard severity scores for predicting hospital mortality in sepsis patients. methods: a retrospective analysis was conducted in a medical intensive care unit of a tertiary university hospital. the performance of severity scores was evaluated by discrimination, calibration, and overall performance. the primary outcome was in-hospital mortality. results: overall , sepsis patients were enrolled, patients ( . %) were classified to septic shock by sepsis- definition. hospital mortality rate was . %. the nysss predicted hospital mortality . +/- . %, which underestimated prediction with smr . ( %ci . - . ) . however, the sss predicted hospital mortality +/- . %, which slightly overestimated mortality prediction with smr . ( %ci . - . ). the nysss had the moderate discrimination with an auc of . ( % ci . - . ), in contrast to the sss presented good discrimination with an auc of . ( %ci . - . ). the auc of sss was statistically higher than that of nysss (p< . ). nevertheless the apache iv and saps ii showed the best discrimination with auc of . . the auc of the nysss and sss was significant lower than that of apache ii, iii, iv, saps ii and saps ( figure ). the calibration of all severity scores was poor with the hosmer-lemeshow goodness-of-fit h test < . . the nysss was the lowest overall performance with brier score . . the apache iv present the best overall performance with brier scores . . conclusions: the sss indicated better discrimination and overall performance than the nysss. however the calibration of both sepsis severity scores and another severity score were poor. furthermore, specific severity score for sepsis mortality prediction needs to be modified or customized to improve the performance. introduction: metabolic markers, especially lactate, have been shown to predict mortality in acutely unwell patients. we hypothesised that early changes in metabolic markers over time would better predict mortality and length of stay, with patients who correct their metabolic derangement having lower risk of death and reduced length of stay (los). methods: single centre, retrospective cohort study in a bed icu. we included all patients who had an arterial measurement of lactate, paco , base excess (be) and ph on admission and at hours after admission to icu between / / and / / . the 'clearance' of these markers was calculated using the equation ((value at admissionvalue at hours)/value at admission). clearance calculations only included those patients with deranged results on admission (lactate> mmol/l, be<- mmol/l, ph< . , paco > . kpa). roc analysis was used to predict in-hospital mortality and length of stay, using both the initial admission values, and using the clearance value, as well as icnarc and apache ii scores for comparison. if a patient was admitted twice in the time period, only the first admission was included. results: patients were included (sex ratio . , mean age . ). table ). none of the values tested had a auc greater than . for predicting length of stay. conclusions: the clearances of metabolic markers over the initial hours after icu admission does not provide better prognostic information than the value at admission. initial lactate level was the best predictor of mortality, but compared poorly to icnarc score. metabolic markers do not accurately predict length of stay. . - . ) vs . (iiq . - . ), p= . ]. the other hemogram parameters did not differ between groups (table ) . when adjusted for severity score, in patients submitted to emergent surgery, the mpv value was still independently associated with mortality (or . ci . - . , p= . ), and its roc curve (auc) was . to mortality (figure ). conclusions: mpv is a cheap and easily accessible marker which can add prognostic value in this specific population. in the future, we will validate it in a larger cohort of cancer pts admitted to intensive care. haematological malignancy in critical care: outcomes and risk factors c denny introduction: about % of patients admitted to hospital with a haematological malignancy will become critically ill [ ] . life expectancy in these patients is poor with a month mortality of % or more in specialist units [ ] . in contrast, patients without critical illness can expect a year survival rate exceeding % for many cancers. this disparity results in differences of opinion on the best strategy for such patients among haematologists and critical care physicians. we conducted a local quality improvement project to quantify mortality and risk factors in critically ill patients with a haematological malignancy in our hospital. methods: patients admitted to the critical care unit of broomfield hospital, a district general hospital with tertiary specialist services, from january to december with haematological malignancy were included in the analysis. patients in remission for more than years and patients admitted following elective surgery were excluded from analysis. death in critical care or in hospital after critical care discharge were the primary outcomes. mortality was correlated with demographic data using simple statistical measures and regression analysis. results: patients were included in the analysis. overall mortality was %(n= ). survivors tended to be younger ( vs years) but had similar clinical frailty scores. early critical care admission (within hours) was associated with better survival ( . vs . %). nonsurvivors had a greater incidence of sepsis and respiratory failure, and required more ventilatory and vasopressor support. mortality was higher in patients requiring more than one organ support. conclusions: the overall mortality in our data is lesser than previously published data but supports the conclusion that mortality is determined primarily by the number of organs supported with the effects of malignancy playing a secondary role. (figure ). increasing levels of frailty were associated with increasing risks of death at year (p< . ) (figure ). frailty significantly increased -year mortality hazards in unadjusted analyses (hr . ; %ci; . - . ; p< . ) and covariate-adjusted analyses (hr . ; %ci . - . ; p= . ) ( table ) . conclusions: frailty was common and associated with greater age, more severe illness and female gender. frailty was significantly associated with heightened mortality risks in both unadjusted and covariateadjusted analyses. frailty scoring may encapsulate variables affecting mortality which are omitted in current predictive systems, making it a promising risk stratification and decision-making tool in icu. fig. (abstract p ) . unadjusted survival curves stratified by frailty status. frail patients were statistically significantly less likely to survive to year plateau at day = , delta peak= and hpr= . . were assigned respectively a point value of , , and to these predictors based on their beta coefficient in the predictive model. the score yielded a roc-auc: (auc= . ; %ci, [ . - . ]; p= . ). using the validation data set (n= ), the score had an roc-auc= . and similar estimated probabilities for mortality. conclusions: the paw-mps seems to demonstrate interesting discriminative properties to predict mortality. what is the role of the pulmonary embolism severity index (pesi) and rv/lv ratio as clinical risk assessment tools for patients undergoing ultrasound-assisted catheter-directed thrombolysis (uacdt)? introduction: to evaluate if the pulmonary embolism severity index (pesi) score correlates with rv/lv ratio, biomarkers of cardiac injury, fibrinogen and length of stay(los). also to evaluate the correlation between rv/lv ratio with biomarkers of cardiac injury, fibrinogen and los for patients who underwent uacdt. methods: a retrospective review of patients with sub-massive pulmonary embolism (pe) who underwent ultrasound-assisted catheterdirected thrombolysis (uacdt) was performed. pesi score, rv/lv ratio, length of stay(los), fibrinogen levels, troponin levesl, and brain natriuretic peptide(bnp) levels, were calculated and collected prior to uacdt. spearman's rank correlation coefficient was calculated for all non-parametric variables. results: patients, males and females, were included in the study. the mean (±sd) age was ± years. the mean pesi score was ± . mean rv/lv ratio was . ± . . a significant correlation between the rv/lv ratio and both fibrinogen and troponin level (p= . , p= . ) was noted. no significant correlation existed between pesi score and rv/lv (p= . ). no significant correlation existed between both rv/lv ratio and pesi score with length of stay (p= . ) after uacdt. there were no noted mortality or complications. conclusions: pesi score is used as a prognostic factor for the patients with pe, however, our study shows that pesi score does not correlate with rv/lv ratio or length of stay after the uacdt. there was inverse correlation between rv/lv ratio and fibrinogen. there was also positive correlation between rv/lv ratio and troponin for patients with and without heart failure. according to our data, there may be limited use of pesi score and rv/lv ratio for risk stratification of pe patients undergoing uacdt. introduction: conventional scores for prediction of risk and outcome, such as sapsii and sofa, have not been validated for patients admitted to level ii critical care units (intermediate level or imcus). we compared the performance of sapsii and sofa scores with the intermediate care unit severity score (imcuss) in a general population admitted to imcu. methods: we conducted a prospective observational cohort study in a -bed level ii-iii icu from a university-affiliated hospital, during a three-month period. we applied sapsii, sofa day one and imcuss to all patients admitted during that period. primary outcome was a composite of hospital mortality and need to increase level of care. additionally, we tested the relevance of each variable within each score to predict the outcome. results: we included patients with a mean age of . ± . years. patients were considered "step-down" (transferred from our level iii beds), and the remaining originated from the emergency conclusions: months after completion, the primary care management intervention had no effect on mental health-related quality of life and physical function among survivors of sepsis. increase in ptsd symptoms in the control group may suggest a possible protective effect of the intervention. introduction: critically ill patients and their families are often confronted with an overwhelming amount of clinical information shortly after hospital admission. their reliance on internet resources for additional information is increasing, particularly for unfamiliar medical terminology. yet, little is known about whether these online resources meet the recommended reading level and complexity appropriate for the average reader. methods: an online search of websites containing four common critical care diagnoses in the icu (respiratory failure, renal failure, sepsis and delirium) was performed. a total of readability formulas were used. the flesch-kincaid grade reading level (grl) and flesch reading ease (fre) were used in the final analysis. document complexity was evaluated using the pmose/ikirsch formula. results: websites on respiratory failure were written at the th grl with fre of . . renal failure resources had a th grl with fre of . . sepsis websites had an th grl with fre of . . delirium websites had a th grl with fre of . . when comparing website types (government, non-profit and private), anova showed a difference in fre across all groups and government websites had a conclusions: online resources used by intensive care unit patients and families tend to be written at higher than the recommended th grl, with government sites better meeting this target than nonprofit and private organizations. online resources should be improved to lower this unfortunate barrier to patient education. introduction: the recent enactment of the data protection act , the general data protection regulations, and a series of data breaches in the healthcare sector, have renewed interest in how our patients' information is collected, used and shared. the complex framework of laws and regulations governing the use and disclosure of personal data may lead to professional and financial consequences if information is disclosed inappropriately. disclosures to the police when they concern incapacitous patients are particularly challenging, as the disclosure may have no direct benefit to the patient and may cause the patient considerable harm. methods: we have reviewed the relevant laws and regulations to identify the circumstances in which doctors must release information regarding incapacitous patients to the police. the laws and regulations are examined to identify the extent of the disclosure required, and any requirements for the disclosure to be lawful. we have also identified laws which confer a power to disclose information about incapacitous patients, and the circumstances in which these powers can be used. results: in conjunction with a local police constabulary we have developed an information request form which makes it easier for those requesting and disclosing information to understand the legal basis of the disclosure. we have also developed guidelines to allow practitioners to understand where a disclosure is obligatory or discretionary. conclusions: the next stage of the project is to audit disclosures of information in the intensive care unit, and identify whether information is being released lawfully and following the correct procedure. introduction: family members are affected both physically and psychologically when their relative is admitted to icu. there is limited knowledge describing their experiences and structured interventions that might support them during their relative's critical illness. the aim of this review is to describe published literature on the needs and experiences of relatives of adult critically ill patients and interventions to improve family satisfaction and psychological well-being. methods: design: scoping review. standardised processes of study identification, data extraction on study design, sample size, sample characteristics and outcomes measured (figure ) . results: from references, studies were identified for inclusion four key themes were identified: ) different perspectives on meeting family needs ) family satisfaction with icu care ) factors impacting on family health and well-being and capacity to cope ) psychosocial interventions conclusions: family members of patients in icu experience unmet information and assurance needs which impacts on their physical and mental health. structured written as well as oral information show some effect in improving satisfaction and reducing psychological burden. icu's who are able to support interventions based on meeting family information needs, in addition to reducing psychological burden and increasing satisfaction will enable each family to provide more support to their relative within the icu. introduction: unmet informational needs lead to dissatisfaction with care and psychological distress. identifying interventions to help meet specific needs is a crucial and necessary step in providing family centred care in icu. we aimed to implement and evaluate the impact of delivering a structured communication strategy on levels of anxiety, uncertainty and satisfaction with care and decision making in families of critically ill adults. methods: a quasi experimental study with pre and post test design. a convenience sample of family members were recruited from july to february . the intervention group (n= ) received both oral and printed information to guide them in preparing for a structured family meeting. the control group (n= ) received usual fig. (abstract p ) . article selection process for scoping review routine care and existing family informational support. anxiety, uncertainty and family satisfaction were measured in the two groups on icu admission and icu discharge. results: mean anxiety, uncertainty and satisfaction with care and decision making scores pre and post intervention were compared. there were no significant differences in mean anxiety, uncertainty or satisfaction scores between the two groups before the intervention (p> . ). mean scores on anxiety ( . vs . ), and uncertainty ( . vs . ) were lower post intervention, but not significantly so ( figure & ). total satisfaction, satisfaction with care and satisfaction with decision making mean scores were similar in both groups before and after the intervention (p. . ). conclusions: providing relatives with a combination of targeted written and oral information delivered by nursing and medical staff reduced anxiety and uncertainty with this reduction being evident through to discharge from icu. although not statistically significant, there was what may be seen as a suggestion of a clinically significant drop in anxiety and uncertainty following the intervention introduction: clinical studies in intensive care unit (icu) patients are warranted in order to improve healthcare. the aim of this study was to analyse barriers and challenges in the process of achieving informed consent from icu patients. methods: we analysed patients considered for inclusion in a prospective observational study of venous thromboembolism in the icu, i.e. the norwegian intensive care unit dalteparin effect (norides) study. data were collected from the screening log, consent forms and associated research notes of the norides study. results: we observed that of ( %) eligible patients according to inclusion and exclusion criteria were omitted from the nor-ides study due to barriers and challenges in the process of receiving informed consent. were categorized as psychiatric diseases consisting of known psychosis or recent suicide attempt, likely or actual treatment withdrawals and due to language barriers among non-norwegians. among the patients included in the norides study, ( %) consents were from patients and ( %) obtained from their next of kind. from the patient consents, ( %) consents were oral and ( %) were written. patients were physically unable to sign, and patients did not recognize their own signature. the study further pointed at some specific challenges in the process of consent, herein questionable competence to give consent, failure to remember being asked/included, inability to separate research from treatment etc. there were also difficulties in evaluating who was next of kin and how to reach them. conclusions: barriers and challenges in obtaining informed consent from icu patients led to exclusion of one fifth of the eligible patients in our study. informed consent directly from patients was obtained from less than half of the included patients. obstacles in the process of achieving informed consent were practical, medical, ethical and/or legal. determinants of end-of-life decision-making in the intensive care unit p eiben, c brathwaite-shirley, s canestrini king´s college hospital nhs foundation trust, london, united kingdom critical care , (suppl ):p introduction: although the majority of intensive care unit (icu) deaths follow the decision to forgo life sustaining treatment (lst), variability in patterns is commonly observed [ , ] . we reviewed end of life (eol) practice at our institution in order to explore: (i) patient characteristics affecting eol decision-making, (ii) communication among surrogate decision-makers, and (iii) eol management. methods: we retrospectively analyzed data from consecutive patients who died in our ten-bed icu over months (study period). patient demographics, apache ii, functional status, diagnosis on admission, icu length of stay (los) were collected; family/next-of-kin (nok) involvement and rationale for lst limitation were recorded ( conclusions: our analysis shows that in our institution eol deliberations follow a shared decision-making process. lack of family/nok involvement and incomplete documentation was exceptional. the significant difference in los between w-group and nw-group, in the face of similar apache ii, warrants further investigation. vae calculator rheumatology review . van der jagt m. crit care consensus on circulatory shock and hemodynamic monitoring. task force of the european society of intensive care medicine cardiac output monitoring: how to choose the optimal method for the individual patient perioperative cardiovascular monitoring of highrisk patients: a consensus of guidelines for nutrition support therapy in the adult critically ill patient references . nice guideline for aki: prevention, detection and management serial creatinine results pre-and post ecmo references . polit et al. research in nursing & health reference . sherliker et al national blood transfusion committee, nhs blood and transplant arch otolaryngol head neck surg fig. (abstract p ). rsi agent guideline references . nuckton tj nejm icm baseline characteristics reference elso guidelines for cardiopulmonary extracorporeal life support s -leitlinie invasive beatmung und einsatz extrakorporaler verfahren bei akuter respiratorischer insuffizienz .auflage p handgrip strength does not predict spontaneous breathing trial failure or difficult or prolonged weaning of critically ill patients g friedman total burn care introduction: we aimed to evaluate safety and efficacy of light sedation with dexmedetomidine (dex-ls) in acute brain injury (abi) patients. methods: retrospective analysis on icu patients with traumatic/medical abi, out of the neuroprotection window and undergoing dex-ls. data of pre-infusion and infusion periods were compared. results: patients (age ± , males . %) were included. traurespectively. conclusions: dex-ls among icu patients affected by abi turned out to be feasible and safe. it enabled discontinuation from mv and maintenance of spontaneous breathing in the majority of cases %) delirious patients and of ( . %) non-delirious patients could be discharged from the hospital. we evaluated the -year mortality in the hospital survivors. results: totally, patients participated in our study. the majority of them ( . %) were male with the median age of [ , . ] years and the median apache ii score on the first day of icu admission of risk of delirium was associated with preoperatory euroscore ii (p= . ) and history of previous cardiac surgery (p= . ). moreover, in the intraoperatory period the risk of delirium was associated with red blood cell transfusion, intervention for aortic dissection (p= . ), hypothermic circulatory arrest (hca) with anterograde cerebral perfusion (acp) (p= . ) (table ). in the postoperatory period risk of delirium was associated with levels of creatinine clearance (p= . ) and c-reactive protein (crp) (p= . ). conclusions: delirium is relatively frequent in the cardiac surgical icu patient journey of group : those patients discharged directly home from critical care unit poor compliance with co-signing in icca ( %, n= ) compared to paper ( %, n= ) (figure ) and the reported difficulty in co-signing ( %, n= ) reveals significant usability concerns and potential safety issues. % (n= ) found icca intuitive, though % (n= ) found navigating the interface difficult and reported concerns with losing saved work ( %, n= ). conclusions: this study highlights important usability issues that may impact staff satisfaction th national audit project of the royal college of anaesthetists and the difficult airway society. major complications of airway management references . guidelines for provision for intensive care services (gpics), version medicines optimisation: the safe and effective use of medicines reducing harm from omitted and delayed medicines. a tool to support local implementation p understanding the delivery of intensive care in south p mobilising ventilated patients early with interdisciplinary teams (move it) singapore general hospital, department of respiratory and critical care p validation of boyd criteria and possum-score on mortality and morbidity in general surgical intensive care unit k chittawatanarat, y chatsrisuwan faculty of medicine pts with central nervous system neoplasms or submitted to elective surgeries were excluded. descriptive analysis and χ test, pearson´s, wilcoxon rank-sum, uni and multivariate logistic regressions were used when appropriate. results: from a total of pts identified, . % (n= ) were admitted after emergent surgery and . % (n= ) for medical reasons. global icu mortality was . % (n= ). in comparison to survivors, the patients that died had a similar age were recorded data regarding demographics, clinical variables, paw (at admission and at day ), high pressure ratio (hpr = number of days with high pressures: peak ≥ and/or plateau ≥ ; and/or driving pressure ≥ ; and/or auto-peep ≥ ; divided by los), trends of paw (paw at day -paw at admission) and outcomes. the patients were divided into two groups: a construction group (n= ) and a validation group(n= ). the paw-mps was developed and validated by analyzing in a multivariate regression model the different paw ± . ; pco , ± mmhg paw were respectively for peak, plateau, driving, and auto-peep at admission: ± , . ± , . ± and three independent mortality risk factors were identified centro hospitalar do porto p five-year mortality and morbidity impact of prolonged icu stay n van aerde , g hermans laboratory of cellular and molecular medicine we investigated differences in mortality and morbidity after short (< days) and prolonged (≥ days) icu-stay. methods: prospective, -year follow-up study of former epanicpatients (clinicaltrials.gov:nct , n= ). mortality was assessed in all. for morbidity analyses, all long-stay and a random sample ( %) of short-stay survivors were contacted. primary outcomes were total and post- -day -year mortality in multivariable cox regression analysis, icu-risk factors comprised hypoglycaemia, corticosteroids, nmba, benzodiazepines, mechanical ventilation, new dialysis, new infection, liver dysfunction, whereas clonidine may be protective. among long-and short-stay -year survivors hgf, mwd and pf sf- were lower in long-stayers mwd: % ( %ci: %- %) vs % ( %ci: %- %) multivariable regression identified associations with benzodiazepines (hgf and pf-sf ), vasopressors (pf-sf ) and opioids ( mwd) ptsd related symptoms were accessed with the post traumatic stress syndrome questions inventory (ptss- ) at the post icu follow up clinic, six months after the acute stress event. the post icu consultation was carry out by an icu doctor and an icu nurse. exclusion criteria: previous severe psiquiatric disorders, not able to respond the questionnaire medical %, surgical % and trauma %. patients ( %) were on imv and the median ventilation days was . ptsd scores ranged from to . delusional memories were conclusions: in this study the rate of ptsd was lower . % and related with a lower saps ii and the presence of memories of the icu stay. no relation was found with delusional memories, imv or superior icu length of stay. patients with lower illness severity and without imv, should be elective to the follow up-clinics. p long-term effects of a sepsis aftercare intervention k schmidt united states; jena university hospital patras general university hospital, intensive care unit, patras, greece; patras general university hospital, division of infectious diseases results: ( . %) patients were readmitted within hours and ( . %) in to days. the two groups didn't differ in age, gender, charlson comorbidity index and length of stay on both admissions. elective surgery was the most common type of admission ( . %) followed by medical ( . %), emergency surgery ( %) and trauma ( . %). the mean time to readmission in the late group was . (± . ) days. patients in the late group had higher apache ii score on their first and second admission, ( . ± . vs . ± . ; p= . ) and ( . ± . vs . ± . ; p= . ) respectively. respiratory insufficiency was the most common cause of readmission in both groups followed by sepsis and cardiac arrest. finally in the early group p introduction: in intensive care units, perceived inappropriate treatments (pit) have been associated with negative impact on caregivers univariate analysis revealed that burn-out, pit and intention to leave were greater in units where nurses´teams included no activity in the icu, compared to "shared" work in icu and idtcu. in multivariate analysis, perception of non beneficial treatment of patients with life support witholding was associated with: bad collaboration with other units p profile of intensive care unit (icu) patients on whom life-sustaining medical treatment were withdrawn or withheld s chatterjee variables collected-age, sex, apa-che iv score, diagnostic-category and co-morbidities. primary outcomes were icu and hospital mortality. secondary outcomes included icu and hospital length of stay(los) female sex, n (%) ( . %) diagnosis on admission: medical, n (%) rrt at time of wlst, n (%) ( . %) dnr order, n (%) ( . %) organ donation services involved, n (%) ( . %) introduction: high flow nasal cannula(hfnc) is a new modality in respiratory failure management [ ] . this study objectively held to compare the physiological outcomes in the non-invasive ventilation(niv) treatment of cardiogenic acute pulmonary oedema(apo) patient in the emergency department(ed) delivered by helmet cpap(hcpap) and hfnc. methods: single-centre randomized controlled trial on patients presenting with cardiogenic apo. primary endpoint was a heart rate reduction.secondary endpoints included: improvement in subjective dyspnoea scales, respiratory rate, blood oxygenation, intubation rate and days mortality rate. results: patients were enrolled and randomized ( patients to hcpap; to hfnc) ( to . ± . ). intubation rate was lower in hcpap ( . % for hcpap versus . % for hfnc) and days mortality rate is lower in hcpap ( . % for hcpap versus . % for hfnc). conclusions: both hcpap and hfnc significantly improved patient condition in patient presenting to the ed with cardiogenic apo. however, hcpap was better than hfnc in improving physiology outcomes, lower intubation rate and mortality rate in patient introduction: the aim of the study was to compare the confusing assessment method of the intensive care unit (cam-icu) and the nursing delirium scoring scale (nu-desc) for assessment of delirium in the icu. furthermore we wanted to test the interpersonal variation of the nu-desc. delirium is proved to be associated with increased mortality [ ] . nu-desc is an observational five-item scale that does not require patient participation and is adapted to the fluctuating nature of delirium. each item can be scored from to . delirium is defined with a score > . the nu-desc has recently been translated into danish (nu-desc dk) but has not been validated.methods: icu patients, who met the inclusion-criteria for the cam-icu were scored with both cam-icu and nu-desc dk. patients were scored of two independent nurses at approximately the same time every day.results: a total of patients were enrolled, and comparisons between cam-icu and nu-desc dk were registered ( figure ).there was agreement between nu-desc and cam-icu in of registrations (hereof registrations were delirium negative). in interpersonal variation, registrations were made. the conclusion was identical in % of registrations, but only % agreed in all scoring-scale items (all negative).conclusions: a high agreement between nu-desc and cam-icu was found however the comparison was based on predominately patients with negative delirium score. the interpersonal variation of nu-desc scoring was substantial. a future validation of the nu-desc dk as a screening tool in the icu requires thorough training and instructions to minimize interpersonal variation. introduction: an increasing number of patients are being discharged directly home from critical care units and this is currently viewed as a negative quality indicator [ ] . the purpose of this audit was to characterise a cohort of patients who can be safely discharged directly home from adult critical care at st thomas´hospital (sth). methods: retrospective observational study of two groups of patients; ) those discharged directly home from critical care, ) those discharged within two days of step down to a ward from critical care (admissions st june- st october ). the clinical notes of these patients were reviewed via online systems. results: baseline demographics of the patients in group and patients in group were similar (mean age of years, versus years, p= . ); average length of stay in critical care was also similar ( . days versus . days respectively p= . ). in group , of icu days were after considered fit for step down versus of days in group , p= . (fig , ) . in group , drug related presentations were more common ( % versus % p= . ), fewer patients had specialist follow up post discharge ( % versus %, p< . ). in group , patients ( %) were readmitted within days, to critical care. in group , patients ( %) were readmitted, to critical care (p= . and . respectively); none of these readmissions were felt to have been preventable.conclusions: there is a cohort of patients suitable for discharge directly home from critical care who did not spend significantly longer in icu awaiting discharge than those who were stepped down to the ward. identifying these patients early, potentially by their diagnosis, and creating a pathway including access to specialist follow up clinic could allow prompt discharge directly from critical care, thus improving patient satisfaction and reducing hospital-acquired morbidity healthcare costs [ ] . the evaluation of the usability of a critical care information system ( introduction: critical care information systems (ccis) support clinical processes by storing and managing data, but poor usability can lead to staff dissatisfaction and increased workload, promoting workarounds that may compromise patient safety [ ] . the purpose of the study was to evaluate the usability of a philips intellispace critical care and anaesthesia (icca) ccis, recently implemented in beds across three critical care units of a large uk teaching hospital. methods: a prospective, mixed method observational study conducted in may , comprising of ( ) an audit assessing the ease of linking bedside devices to icca, ( ) an audit assessing the usability of co-signing medications in icca compared with a non-icca paper factors that commonly drive workforce metrics may not correlate with staff perceptions of safety. the bpr is a pragmatic, staff driven, tool to augment other measures of safety and is applicable to various icu settings. further research is needed to explore staff perceptions in order to understand the importance of this organisationally, and for staff stress. ventilator-free duration in icu, central venous catheter duration, urinary catheter duration, rates of deep vein thrombosis (dvt) and stress ulcer prophylaxis, rates of de-escalation antibiotic therapy, dvt prophylaxis duration, stress ulcer prophylaxis duration, icu and hospital mortality, -day mortality, rate of central venous catheter infection, length of stay in icu and hospital between two groups were analyzed. results: rate and duration of dvt prophylaxis in the intervention group were . % and ( , ) days respectively, in the control group were . % and ( , ) days, the differences between two groups were statistically significant(p< . ) ( table ). there were no differences in ventilator-free duration in icu, central venous catheter duration, urinary catheter duration, rate of stress ulcer prophylaxis, rates of de-escalation antibiotic therapy, stress ulcer prophylaxis duration, icu and hospital mortality, -day mortality, rate of central venous catheter(cvc) infection, length of stay in icu and hospital between two groups ( table ) . conclusions: electronic checklist in ward rounds can increase the rate of dvt prophylaxis and reduce the duration, but it cannot improve the prognosis of critically ill patients. introduction: the goal of the project "i see you" is family-centeredcare based on family meetings that improve the experience of the patient´s family members during hospitalization in the icu. the meetings focus on relaying information, raising knowledge and addressing the social and emotional needs of families. providing support along with information was found to be the strongest predictor of family satisfaction and could lead to improve cooperation between family and staff [ ] .methods: meetings and questionnaire: family meetings consist of a multidisciplinary team, a group facilitator and combined with a multimedia presentation about the unit and equipment. in addition, they focus on social and emotional needs: managing daily routine, sharing problems, fears and anxieties and more. at the end of the session a questionnaire was given to assess the impact of the intervention. sharing data: at the end of the first quarter, the data from meeting was summarized and sent to the staff alongside tools for effective communication.results: the project began in february . to date, family members of patients have attended the sessions. the topics discussed by the participants include: contact with the patient, prevention of infections, procedures, visits, conversations with doctors, medical confidentiality; guardianship; tracheotomy and social issues (fig ) . a sample of questionnaires was transferred to participants report satisfaction at a very high level.conclusions: the meeting received a very positive feedback from the participants. the project has achieved its goals and therefore it has been decided to be continued.introduction: possum score and boyd criteria are used to predict the outcome for high risk surgical patients. the aim of this study was to validation of these two measurement tools on mortality and morbidity in a university-based surgical intensive care unit (sicu) in thailand.methods: nine hundred and fifty two patients were enrolled onto this prospective review. all patients who had been admitted to sicu in a university-based hospital were included. all patients were collected for boyd criteria and possum score and outcomes and morbidity during sicu admission and discharge. introduction: aromatic microbial metabolites (amm), such as phenyllactic (phla), p-hydroxyphenylacetic (p-hphaa), and phydroxyphenyllactic (p-hphla) are involved in the pathogenesis of septic shock and are associated with mortality [ ] . according to previous studies, amm have a high prognostic value in patients with abdominal infection [ , ] . we hypothesize that amm have the prognostic value in patients with pneumonia in icu. methods: data of patients with community-acquired pneumonia was obtained on admission to icu. the levels of amm (phla, p-hphla and p-hphaa) were measured in blood serum using gas chromatography with flame ionization detector and compared in groups of patients: with favorable and with lethal outcome (mann-whitney utest). spearman's correlations between amm and clinical and laboratory data were calculated. using method of logistic regression and roc analysis, we measured the prognostic value of amm. (table ) . it was revealed, that some amm have similar prognostic characteristics in comparison with sofa and curb- scales; high level of amm is associated with high risk of death (roc-analysis - fig. ) .conclusions: serum concentrations of amm can be used as independent and practical criteria for the assessing of prognosis in patients with infection in icu. introduction: frailty in the critically ill is associated with increased morbidity and mortality but the optimal timing of frailty assessment, how to best measure frailty, reasons for adverse outcomes and how critical illness impacts frailty are unknown [ ] . in preparation for a multi-center study designed to address these knowledge gaps, we conducted a pilot study whose aim was to assess feasibility as determined by recruitment rates, ability to assess frailty at icu admission and hospital discharge, ability to measure icu and hospital processes of care and ability to conduct -month assessments. conclusions: a multi-center study is feasible but follow-up losses due to mortality and inability to return for assessment will require sample size adjustment. frailty characterization is method dependent, can be done on hospital discharge but varies with time of assessment. these findings will need to be confirmed in our larger study currently in progress. introduction: given the ageing of the world´s population, the demands of critical care resources for elderly patients has increased during the past decade. however, little is known about quality of life and outcomes of elderly icu survivors. the aim of the study is to assess outcomes of elderly icu survivors at least months after discharge: quality of life and mortality. methods: it is a retrospective study performed in a medical adult icu between january to december . the study included all elderly survivors ( ≥ years) after icu admission. outcomes were assessed by telephone interviews at least months after icu discharge. the primary outcome was assessing the quality of life after icu stay, measured by euro qol d questionnaire. the eq- d descriptive system contains five dimensions (mobility, self-care, usual activities, pain and discomfort, and anxiety and depression). for each dimension, there are five levels (no problems, slight problems, moderate problems, severe problems and unable to/extreme problems figure . conclusions: most elderly survivors patients showed a good health related quality of life using the euroqol d- l after icu discharge. fig. (abstract p ) . quality of life (euroqol d) scores after icu discharge introduction: sepsis survivors face mental and physical sequelae even years after discharge from the intensive care unit (icu). effects of a primary care management intervention in sepsis aftercare were tested. exploratory analyses suggest better functional outcomes within the intervention group compared to the control group at six and months after icu discharge. longer term effects of the intervention have not been reported. methods: a randomized controlled trial was conducted, enrolling patients who survived sepsis (including septic shock), recruited from nine german icus. participants were randomized to usual care (n= ) or to a -months intervention (n= ). the intervention included training of patients and their primary care physicians (pcp) in evidence-based post-sepsis care, case management provided by trained nurses and clinical decision support for pcps by consulting physicians. usual care was provided by pcps in the control group. the primary outcome of the trial was the change in mental healthrelated quality at -months after icu discharge. secondary outcomes included measures of mental and physical health. data were collected by telephone interviews using validated questionnaires at the -months follow-up ( months after the -year intervention).results: [ . %, intervention, control] of patients completed the -months follow-up. unlike the intervention group, the control group showed a significant increase of posttraumatic symptoms (diff. ptss- to baseline, mean (sd) . ( . ) control vs.- . ( . ) intervention; p= . ). there were no significant differences in the mcs and all other secondary outcomes between intervention and control group.introduction: survivors of sepsis often show symptoms of posttraumatic stress disorder (ptsd). only few studies report on courses of more than month after discharge from the icu. the aim of this study was to identify predictors for changes in ptsd symptoms over time up to month. methods: follow-up data of the smooth triala rct to evaluate a primary care management intervention on sepsis survivorswere analyzed. included patients were surveyed by phone for ptsdsymptoms at one, , and months after discharge from icu using the post-traumatic-stress-scale (ptss- ). scores changes between follow-up periods were analyzed using latent-change scores in structural equation models. predictors were clinical and sociodemographic baseline characteristics as well as physical, cognitive and functional sepsis sequelae assessed by validated questionnaires.results: patients were included of which participated in the month follow-up. a decrease of ptsd symptoms between and months was predicted by higher education (b=- . , p= . ), while higher pain intensity at one month predicted an increase (b= . , p= . ). increasing ptsd symptoms between and months were predicted by reporting more than two traumatic memories at one month (b= . , p= . ), more sleep problems (b= . , p= . ) and worse cognitive performance at months (b=- . , p= . ) as well as more neuropathic symptoms at months (b= . , p= . ).conclusions: sepsis patients that suffer from physical, cognitive and functional impairments after icu discharge may be at increased risk for developing late-onset ptsd. these predictors need to be replicated by future studies. early versus late readmission to the intensive care unit: a ten-year retrospective study v karamouzos , n ntoulias , d aretha , a solomou , c sklavou , d logothetis , t vrettos , m papadimitriou-olivgieris , d velissaris , f fligou conclusions: icu patients whose life-sustaining treatment was withdrawn or withheld had higher illness-severity scores, were older, had longer icu los and higher mortality than those in active-treatment group. healthcare introduction: caring for the critically ill patient is a complex task and becomes tougher when a death process takes place. a number of needs and coping strategies emerge from the healthcare providers before these issues but are mostly displayed out of individual skills and intuition. if those approaches are unappropriate and the needs are not met, patients' death process may be burdensome for caregivers. this could affect the quality of care for patients and families during the whole end-of-life care process. the aim of our study was to explore the different needs and coping strategies used by icu healthcare providers when facing patients in the dying process. methods: qualitative and collective case study. ten semi-structured interviews were conducted in icu personnel ( physicians and nursing professionals). a thematic analysis was done using nvivo software. local ethics committee approved the study. results: respondents were % women, had . ± . years-old and . ± . years of icu experience. main needs identified in icu healthcare providers refer to a lack of tools for doing emotional containment when delivering bad news to families, handling personal mourning, the need to perceive consistency regarding end-of-life care management across the icu team, and a wish of having regular training from a psychologist. main identified coping strategies included closing rituals, finding quiet spaces to spend time, and asking for counselling with more expert colleagues. a need for systematic, although basic training on these issues from qualified professionals is demanded. conclusions: usually, basic needs from patients and families in the process of dying are well addressed, but healthcare providers' needs are underrecognized and coping strategies mostly unknown. visibilization of those needs and basic but formal training in emotional containment, self-care and coping strategies are greatly desired. introduction: in the intensive care unit (icu), patients often exhibit cognitive impairments that prevent them from participating in decisions related to therapeutic options at the end of life. consequently, their families are often asked to speak for them when difficult decisions must be made. the main of this study was to determine the frequence in wich family want to share in end of life decisions and factors associated with this desire.methods: a prospective study was conducted in one mixed icu in montevideo. relatives of patients were invited to participate in this study after hours in the icu and completed a survey that included the hospital anxiety and depression scale. results: we analized relatives from patients hospitalized in the intensive care unit. the relationship with the patient was as follows: % spouses, % siblings, % grown children, % parents, and % other family members and friends. of them, . % reported a desire to share in end of life decisions. anxiety and depression symtoms were present in % and % respectively. factors asociated with the desire of involvment in end of life decisions by bivariate analysis were: female sex ( % vs %, p= . ), presence of anxiety ( % vs %, p= . ) and patient ecog - ( % vs %, p= . ). multivariate analysis shows that the presence of anxiety is the only independent factor associated with the desire to participate in end of life decisions (or . , ic % . - . ; p= . ). conclusions: have a loved one in icu is often associated with anxiety and depression after hours of admission. only % of the relatives want to participate in end of life decisions. the presence of anxiety is independently associated with the want to share in decisions making process. introduction: intensive care aims to treat failure of vital organ systems. sometimes, a patient's condition is of such a degree that intensive care is no longer beneficial, and decisions to withdraw or withhold intensive care are made. this means that life-sustaining treatments are terminated or not initiated. we aimed to identify variables that are independent factors for the decision to withdraw or withhold intensive care. methods: registry study using extracted data from a national quality registry the swedish intensive care registry (sir) - . data are delivered to the registry by nurses and doctors daily, during each patients' stay in the intensive care unit (icu). a total of , intensive care cases reported to the sir from - . results: data regarding each patient´s age, sex, diagnoses, condition at admission (expressed as simplified acute physiology score version , saps ), comorbidities and registered decisions to withdraw or withhold intensive care were analyzed. of the , cases reported, . % were women and . % men, and . % were - years old. a total of . % received a decision to withdraw or withhold intensive care, accounting for . % of all women and . % of all men, p< . . independent variables associated with increased odds of receiving a decision to withdraw or withhold intensive care were older age, worse condition at admission, and female sex. female sex was associated with an increased odds of receiving a decision to withdraw or withhold intensive care by % (ci . - . %) after adjustments for condition at admission and age. conclusions: older age, worse condition at admission and female sex was found to be independent variables associated with an increased odds to receive a decision to withdraw or withhold intensive care.publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - smgv ma authors: doyle, andrew j; danaee, anicee; i furtado, charlene; miller, scott; maggs, tim; robinson, susan e; retter, andrew title: blood component use in critical care in patients with covid‐ infection: a single centre experience date: - - journal: br j haematol doi: . /bjh. sha: doc_id: cord_uid: smgv ma there has been a significant surge in admissions to critical care during the covid‐ pandemic. at present, the demands on blood components have not been described. we reviewed their use during the first weeks of the outbreak from (rd) march in a tertiary‐level critical care department providing veno‐venous extracorporeal membrane oxygenation (vv‐ecmo). patients were reviewed ‐ not requiring ecmo and requiring vv‐ecmo. in total, patients required blood components during their critical care admission. red cell concentrates were the most frequently transfused component in covid‐ infected patients with higher rates of use during vv‐ecmo. the use of fresh frozen plasma, cryoprecipitate and platelet transfusions was low in a period prior to the use of convalescent plasma. since the outbreak of the covid- pandemic, there has been a surge in admissions to intensive care departments. at present it has not been described whether there is an increased blood component requirement in patients with covid- infection. coagulopathy is present in - % of cases and is related to disease severity and worse survival outcomes (lee et al, ) . prothrombotic markers such as fibrinogen and d-dimer are increased with covid- infection with an absence of significant rates of disseminated intravascular coagulation (dic) but higher incidence of thrombosis (klok et al, ; yin et al, ) . restrictive transfusion practice of red blood cells in critical care and extracorporeal membrane oxygenation (ecmo) has similar survival outcomes to liberal transfusion practice (herbert et al, ; klein, ; doyle et al, ) . there is concern that covid- infection disproportionately affects the black, asian and minority ethnic (bame) population (cato et al, ) . blood group disparity between donors and recipients in the united kingdom, particularly from different ethnic groups affected by covid- , may therefore be a potential issue (lattimore et al, ) . our centre provides extensive regional critical care facilities including venovenous extracorporeal membrane oxygenation (vv-ecmo). patients requiring ecmo have increased use of blood components particularly if they bleed (doyle et al, ; agerstrand, ) . in anticipation of increased hospitalisations and a decline in blood donation due to social distancing measures, elective major surgery has largely been postponed in keeping with nationwide policy. we aim to evaluate the current blood product usage, the demographics of those requiring blood components, and their requirements and indications. a prospective database of patients with covid- infection admitted to critical care was reviewed to identify appropriate patients. dates of inclusion were from rd march to th april inclusive. blood traceability is maintained on winpath laboratory integrated management system (chertsey, united kingdom) with transfused blood components identified from this during critical care admissions. blood components included were red cell concentrate (rcc), platelets, fresh frozen plasma (ffp) and cryoprecipitate. blood groups were identified from the isoft clinical manager electronic patient records software (sydney, australia). data were screened on st april . indications for blood component this article is protected by copyright. all rights reserved transfusion were evaluated against the national blood transfusion committee (nbtc) indication code for transfusion (june ) (nbtc, ). as transfusion during ecmo is not included in the nbtc policy, a rcc transfusion trigger of haemoglobin < g/l is adopted locally. all patients received weight-and renal function-dose adjusted chemical thromboprophylaxis unless actively bleeding or required therapeutic anticoagulation. patients were identified for review in the above time period. thirty patients required the use of vv-ecmo, and other patients were admitted to critical care but did not require ecmo support. table iii . rcc was the predominant blood component used. there was low use in platelets, ffp and cryoprecipitate in both ecmo and non-ecmo patients. there were three episodes of non-intracranial major haemorrhages ( % of transfused patients and % of all patients). there was a mean use of units rcc, ffp and . cryoprecipitate in these patients during the bleeding episodes with no platelets transfused. two episodes of exchange transfusion occurred for patients with sickle cell disease (each requiring rcc units). the highest utilisation of platelets was in a patient with acute myeloblastic leukaemia who remained severely thrombocytopenic with sepsis following induction chemotherapy ( units used). despite the increased demands of healthcare resources at the time of the covid- pandemic, it appears that the infection itself does not cause a significant increase in blood component use in comparison to previous data from critical care (chohan et al, ) . there was a lack of other blood requirements or this article is protected by copyright. all rights reserved presence of allo-antibodies in this cohort. there was a predominance of bame patients being treated in comparison to the donor population of the united kingdom, reflected in a higher than expected number of patients with blood group b. there were low rates of major haemorrhage over the period, confined to patients requiring ecmo. as described previously, the use of ecmo showed higher but similar levels of rcc usage, previously estimated at . - . units per day at our centre (doyle et al, ) . this is in comparison . units per day in patients not requiring ecmo in critical care prior to the covid- outbreak (chohan et al, ) . the predominant blood component used was rcc in both patients requiring ecmo and those not requiring ecmo. the most common indications for their transfusion were for maintenance of haemoglobin targets (nbtc codes r and r ) comprising of . % and . % respectively (nbtc, ) . preliminary data from china suggests that anaemia is more prevalent in those with covid- requiring critical care with a progressive fall in haemoglobin over admission (sun et al, ) . although the mechanism of this remains unclear at present, iron dysregulation due to inflammation may be a potential cause. alternative options to red cell transfusion to optimise patient blood management can be considered, such as intravenous iron and recombinant erythropoietin, but their roles in critical care are not well established (baron et al, ; ironman investigators et al, ) . concern of the increased thrombotic rates and inflammatory states in covid- infection in this setting may preclude their widespread use (lee et al, ; klok et al, ; yin et al, ; panigada et al, ) . the use of platelet, ffp and cryoprecipitate transfusions remains low with covid- infection in those who have not had episodes of major haemorrhage. elevated levels of fibrinogen, factor viii and platelets are demonstrated in critical illness in covid- infection suggestive of why transfusion triggers for these components were not met in this patient cohort (lee et al, ; panigada et al, ) . given the prothrombotic tendency of covid- infection, unnecessary transfusion of plasma components should be avoided in the absence of bleeding. a significant decline in blood donation has been shown in china although initial concerns of this in the uk have been offset by a fall in transfusion rates (wang et al, ; nhs blood and transplant, ) . our results suggest that blood component usage as a result of covid- infection remains low with a higher usage in ecmo. optimisation of patient blood management in the critical care setting is one consideration to assist with potential shortages of blood component provision in the next few months. blood conservation in extracorporeal membrane oxygenation for acute respiratory distress syndrome patient blood management during the covid- pandemic -a narrative review the covid- pandemic: a call to action to identify and address racial and ethnic disparities red cell transfusion practice following the transfusion requirements in critical care (tricc) study: prospective observational cohort study in a large uk intensive care unit restrictive transfusion practice in adults receiving venovenous extracorporeal membrane oxygenation: a single-center experience a multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. transfusion requirements in critical care investigators, canadian critical care trials group intravenous iron or placebo for anaemia in intensive care: the ironman multicentre randomized blinded trial: a randomized trial of iv iron in critical illness should blood be an essential medicine incidence of thrombotic complications in critically ill icu patients with covid- blood donors in england and north wales: demography and patterns of donation coagulopathy associated with covid- hypercoagulability of covid- patients in intensive care unit. a report of thromboelastography findings and other parameters of hemostasis abnormalities of peripheral blood system in patients with covid- in impact of covid- on blood centres in zhejiang province china difference of coagulation features between severe pneumonia induced by sars-cov and non-sars-cov this article is protected by copyright. all rights reservedwe would like to acknowledge the dedication of the critical care department at guy's and st thomas' nhs foundation trust during this period. key: cord- -m lw i authors: li, chenglong; hou, xiaotong; tong, zhaohui; qiu, haibo; li, yimin; li, ang title: extracorporeal membrane oxygenation programs for covid- in china date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: m lw i nan the outbreak of coronavirus disease (covid- ) was first reported in wuhan, the capital city of hubei province, and may lead to severe pneumonia and acute respiratory distress syndrome (ards). extracorporeal membrane oxygenation (ecmo), as a temporary life support technique for refractory respiratory or cardiac failure, has been applied in covid- patients [ ] . however, the impact of ecmo on outcomes from covid- was controversial. referring to the present case series and the covid- cohort in china, the mortality of patients undergoing ecmo ranged from to % [ , ] . the chinese society of extracorporeal life support (csecls) performed a survey of ecmo programs for covid- in china, aimed at investigating the program organization and the potential factors associated with outcomes during the pandemic. this voluntary survey was disseminated via e-mail and wechat to ecmo programs registered with the csecls on march , . through march , we had received individual responses from ( . %) ecmo programs in total. when analyzing program characteristics, the program directors' or coordinators' responses were adopted. one hundred eleven individual responses from ecmo programs ( in hubei and outside hubei) applied ecmo in patients with covid- pneumonia and ards were analyzed. respondents included those located in provinces within china before covid- outbroke. twenty-seven respondents belonged to the medical assistance teams which were dispatched to aid hubei and respondents aided other hospitals in their original province, while respondents managed covid- patients with ecmo within their original hospitals. fifty-one of ecmo programs ( in hubei and outside hubei) were organized temporarily in response to the crisis. thirty-two hospitals with temporary ecmo programs did not have any ecmo cases before. the geographic distribution of the ecmo programs and responders' aid to hubei is shown in fig. . patient management characteristics are illustrated in table . compared with ecmo programs in hubei, more programs outside hubei initiated ecmo in older patients ( . % vs . % in age ≥ , p = . ; . % vs . % in age - , p = . ). our findings provide evidence of the current condition of ecmo programs for covid- across china. fifty-one ecmo programs were newly organized. it was most efficient to rearrange medical workers and resources rather than starting new ecmo programs amid the crisis, given that inexperienced ecmo programs and hospitals might lead to unfavorable outcomes. since ecmo is a complicated and highrisk therapy, adequate training and high-volume experience are indispensable [ ] . we also found a difference in age between ecmo patients in hubei and outside hubei. seventy-five percent of covid- cases in china were diagnosed in hubei [ ] . with limited medical resources in hubei, patients with a higher likelihood of survival were chosen to receive ecmo, namely younger patients. however, medical resources were adequate outside hubei. that might be the main reason for more ecmo programs outside hubei applied ecmo in older patients (age > ), aiming at minimizing the local mortality of covid- . age is a key driver of mortality, helping clinicians to select the most appropriate candidates for ecmo among severe ards patients [ ] . however, age should be reconsidered in the discussions of indications for ecmo in covid- . to the limitation, the patient's detailed characteristic was not obtained in the present study. further multicenter registry on covid- patients receiving ecmo support would be performed. to summarize, our large national survey provided detailed information regarding the organization of ecmo programs for covid- in china. to improve outcomes with ecmo during the pandemic, it is key to provide information about ecmo experience, patient selection, and resource allocation to ecmo programs throughout the world. the datasets used in the present study are available from the first author and corresponding authors on reasonable request. ethics approval and consent to participate institutional ethics oversight was considered unnecessary since the present study was a voluntary survey. not applicable. preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study prognosis when using extracorporeal membrane oxygenation (ecmo) for critically ill covid- patients in china: a retrospective case series association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality. analysis of the extracorporeal life support organization registry characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. the respiratory extracorporeal membrane oxygenation survival prediction (resp) score publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -hffj s o authors: schmidt, matthieu; hajage, david; lebreton, guillaume; monsel, antoine; voiriot, guillaume; levy, david; baron, elodie; beurton, alexandra; chommeloux, juliette; meng, paris; nemlaghi, safaa; bay, pierre; leprince, pascal; demoule, alexandre; guidet, bertrand; constantin, jean michel; fartoukh, muriel; dres, martin; combes, alain; luyt, charles-edouard; hekimian, guillaume; brechot, nicolas; pineton de chambrun, marc; desnos, cyrielle; arzoine, jeremy; guerin, emmanuelle; schoell, thibaut; demondion, pierre; juvin, charles; nardonne, nathalie; marin, sofica; d'alessandro, cossimo; nguyen, bao-long; quemeneur, cyril; james, arthur; assefi, mona; lepere, victoria; savary, guillaume; gibelin, aude; turpin, matthieu; elabbadi, alexandre; berti, enora; vezinet, corinne; bonvallot, harold; delmotte, pierre-romain; de sarcus, martin; du fayet de la tour, charlotte; abbas, samia; maury, eric; baudel, jean-luc; lavillegrand, jean-remi; ait oufella, hafid; abdelkrim, abdelmalek; urbina, thomas; virolle, sara; deleris, robin; bonny, vincent; le marec, julien; mayaux, julien; morawiec, elise title: extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with covid- : a retrospective cohort study date: - - journal: the lancet respiratory medicine doi: . /s - ( ) - sha: doc_id: cord_uid: hffj s o summary background patients with covid- who develop severe acute respiratory distress syndrome (ards) can have symptoms that rapidly evolve to profound hypoxaemia and death. the efficacy of extracorporeal membrane oxygenation (ecmo) for patients with severe ards in the context of covid- is unclear. we aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and covid- treated with ecmo. methods this retrospective cohort study was done in the paris–sorbonne university hospital network, comprising five intensive care units (icus) and included patients who received ecmo for covid- associated ards. patient demographics and daily pre-ecmo and on-ecmo data and outcomes were collected. possible outcomes over time were categorised into four different states (states – ): on ecmo, in the icu and weaned off ecmo, alive and out of icu, or death. daily probabilities of occupation in each state and of transitions between these states until day post-ecmo onset were estimated with use of a multi-state cox model stratified for each possible transition. follow-up was right-censored on july , . findings from march to may , , patients with covid- were treated in our icus. complete day- follow-up was available for patients (median age [iqr – ] years and [ %] men) who received ecmo. pre-ecmo, ( %) patients had been prone-positioned; their median driving pressure was (iqr – ) cm h o and pao /fio was ( – ) mm hg. at days post-ecmo initiation, the estimated probabilities of occupation in each state were % ( % ci – ) for state , % ( – ) for state , % ( – ) for state , and % ( – ) for state . ( %) patients had major bleeding and four ( %) had a haemorrhagic stroke. patients died. interpretation the estimated -day survival of ecmo-rescued patients with covid- was similar to that of studies published in the past years on ecmo for severe ards. if another covid- outbreak occurs, ecmo should be considered for patients developing refractory respiratory failure despite optimised care. funding none. the outbreak of severe acute respiratory syndrome coronavirus (sars-cov- ) rapidly evolved into a worldwide pandemic, with more than million cases of covid- as of july , . in france, many disease clusters were identified early in march, , with paris and its surrounding area (greater paris) reporting the most cases. covid- can lead to acute respiratory failure requiring intensive care unit (icu) admission and mechanical ventilation. however, its most serious forms can rapidly evolve to severe acute respiratory distress syndrome (ards) with profound hypoxaemia and death, despite lung-protective mechanical ventilation, including prone-positioning. , in , the extracorporeal membrane oxygenation (ecmo) to rescue lung injury in severe ards (eolia; n= ) trial showed that although mortality in the ecmo group was lower at % compared with % in the control group, the difference was not significant (relative risk · [ % ci · - · ]; p= · ). a post-hoc bayesian analysis of eolia data later showed a high likelihood of an ecmo survival benefit for severe ards, as defined by the eolia entry criteria. accordingly, inter national organisations , and experts in the field , recom mended ecmo for patients who were critically ill with covid- following the initial outbreak in china, further stating that it should be provided in high-volume specialised centres, and a mobile ecmo team should retrieve patients on ecmo from other centres. however, survival was very low in chinese case series of ecmo-treated patients with covid- , , raising concerns about the usefulness of ecmo in this setting. we aimed to establish the characteristics and outcomes of patients who received ecmo for laboratory-confirmed sars-cov- infection in the paris-sorbonne university hospital network icus, the principal hospital referral network for icu care in greater paris, including one of the largest european ecmo centres (pitié-salpêtrière hospital). this retrospective cohort study was done in the paris-sorbonne university hospital network icus (three at la pitié-salpêtrière hospital, one in saint-antoine hospital, and one in tenon hospital), which cared for patients with covid- with severe ards. all consecutive adult patients with laboratory confirmed sars-cov- infection, documented by real-time rt-pcr on nasopharyngeal swabs, or lower respiratory tract aspirates, and who received venoarterial-ecmo or venovenous-ecmo for severe ards were included. patients who received ecmo for isolated refractory cardiogenic shock were excluded. ecmo support was provided at pitié-salpêtrière and tenon hospital icus, while saint-antoine hospital icu cared for patients either before ecmo cannulation or after ecmo decannulation. the sorbonne-university ethics committee (cer-su- - ) approved the protocol. in accordance with the ethical standards of french legislation (committees for the protection of human subjects), informed consent for demographic, physiological, and hospital-outcome data analyses was not obtained because this observational study did not modify existing diagnostic or therapeutic strategies. only non-opposition of the patient or their legal representative for use of the data was obtained. in a context of ecmo resource constraints, all ecmo proposals in greater paris were centralised at pitié-salpêtrière hospital. once contacted, indications for ecmo were evaluated in a staff meeting, including at least two intensivists. patients eligible for ecmo had to fulfill ards criteria, and one of the following disease severity criteria, despite ventilator optimisation (fraction of inspired oxygen [fio ] ≥ %, tidal volume set at ml/kg predicted bodyweight, and positive end-expiratory pressure [peep] ≥ cm of water): ( ) partial pressure of arterial oxygen (pao ) over a fio ratio of less than mm hg for more than h; ( ) pao /fio less than mm hg for more than h; or ( ) arterial blood ph less than · with a partial pressure of arterial carbon dioxide (paco ) of mm hg or more for h or more. physicians were strongly encouraged to use neuromuscular blocking agents and prone-positioning before ecmo. ecmo contraindications were: age older than years, severe comorbidities (eg, advanced cardiac, respiratory, or liver failure; metastatic cancer; or evidence before this study covid- can lead to acute respiratory failure requiring intensive care unit (icu) admission and mechanical ventilation. however, its most serious forms can rapidly evolve to severe acute respiratory distress syndrome (ards) with profound hypoxaemia and death, despite lung-protective mechanical ventilation, including prone-positioning. extracorporeal membrane oxygenation (ecmo) efficacy in this setting is unknown. we searched pubmed for full papers in any language published in peer-reviewed journals up to july , , with the terms "ecmo" and " novel coronavirus", " -ncov", "covid- ", or "sars-cov- ". we identified articles that reported cases of patients infected with sars-cov- who received ecmo for acute respiratory failure. however, these studies included only a limited number of patients (n= to n= ), with limited information on patient characteristics, management, and outcomes. very few of them reported patient survival beyond day post-ecmo onset, precluding any conclusion regarding the usefulness of ecmo in this setting. this retrospective study, with patients included and a complete follow-up until day post-ecmo initiation is, to our knowledge, the largest to date reporting the outcomes after rescue ecmo for the most severe forms of covid- ards, in the paris-sorbonne university hospital network (paris, france), the principal hospital referral network for icu care in greater paris, including one of the largest european ecmo centres (pitié-salpêtrière hospital). our patients' pre-ecmo characteristics indicated extreme ards severity (median pao /fio , [iqr - ] mm hg) although % had been prone-positioned before ecmo onset. the estimated probability of death days post-ecmo initiation was % ( % ci - ). ( %) had major bleeding and four ( %) patients had a haemorrhagic stroke. contrary to preliminary results that indicated dismal outcomes with - % mortality of patients with covid- given ecmo, the estimated % probability of day- mortality for our patients on ecmo was similar to those ecmo-treated in the eolia trial or the large prospective lifegard registry. should another covid- wave occur, ecmo should be considered early for patients developing profound respiratory failure, despite optimised conventional care, including pronepositioning. longer-term follow-up of these patients is now needed to evaluate covid- 's potential pulmonary, physical, and psychological sequelae. haematological malignancies), cardiac arrest (except when cardiopulmonary resuscitation was provided immediately and the low-flow time was < minutes), refractory multiorgan failure or simplified acute physiology score (saps) ii more than , irreversible neurological injury, and mechanical ventilation for more than days. once the indication was approved, the pitié-salpêtrière mobile ecmo retrieval team (mert), comprising a cardiovascular surgeon and a perfusionist, was sent to the patient's bedside for ecmo cannulation, as described previously. , our mert was available h per day, days a week. once ecmo had been implanted, the patient was transferred by a service d'aide medicale d'urgence ambulance with the mert to one of the paris-sorbonne university hospital network icus. ecmo cannulation was done percutaneously under ultrasonography guidance by a cardiovascular surgeon wearing full personal protective equipment (ie, respirator ffp or n mask, gown, goggles, and gloves). for venovenous-ecmo, blood drainage with a large cannula ( ) ( ) ( ) ( ) ( ) inserted into the common femoral vein, and returned through the right internal jugular vein was strongly recommended. for venoarterial-ecmo, a venous drainage cannula ( ) ( ) ( ) ( ) ( ) ( ) ( ) was inserted into the common femoral vein, an arterial return cannula ( ) ( ) ( ) ( ) ( ) into the common femoral artery, and an additional anterograde perfusion cannula was systematically inserted into the superficial femoral artery to prevent leg ischaemia. pump speed was adjusted to obtain blood-oxygen saturation at more than %. optimal cannula positioning was verified by ultrasonography and chest x-ray. following early reports of severe covid- associated coagulopathy [ ] [ ] [ ] and frequent thromboembolic events on ecmo, inclu ding massive pulmonary embolism, , we decided to increase the targeted activated partial thromboplastin time for anticoagulation of venovenous ecmo with unfractionated heparin to - s or anti-xa activity · - · iu/ml (respective values were - s or · - · iu/ml in the eolia trial ) before we treated our first patients with covid- ards. plasma-free haemoglobin and plasma fibrinogen concentrations were monitored daily. the haemoglobin threshold for red blood cell transfusion was - g/dl (or ≤ g/dl when hypoxaemia persisted); platelet transfusions were discouraged except for severe thrombocytopenia (< × cells per l) or thrombocytopenia of more than × cells per l with bleeding. to enhance protection against ventilator-induced lung injury, ultraprotective lung ventilation on ecmo was recommended, , by targeting lower mechanical power delivered to the lungs and lower tidal volume, respiratory rate, and airway and driving pressures. early prone-positioning on ecmo was encouraged in the absence of haemodynamic instability and contraindications for prone-positioning (ie, massive haemoptysis requiring an immediate surgical or interventional radiology procedure; deep venous thrombosis treated for less than days, or single anterior chest tube with air leaks). , , patients were assessed daily for possible ecmo weaning with use of the eolia clinical and physiological criteria. , information recorded before ecmo comprised age, sex, body-mass index, comorbidities, saps ii, sequential organ-failure assessment score, respiratory extracorporeal membrane oxygenation survival prediction score, date of first symptoms, and hospital and icu admissions. information collected before ecmo implantation comprised previous rescue therapies, the date mechanical ventilation started, ventilator settings (mode, peep, fio , respiratory rate, tidal volume, plateau pressure [p plat ]), arterial blood-gas parameters, and routine laboratory values. driving pressure (Δp) was defined as p plat minus peep and mechanical power (j/min) was calculated as follows : ventilatory ratio was calculated as : an expanded dataset including mechanical ventilation settings, arterial blood gases, adjuvant therapies on ecmo, and ecmo-related complications was noted daily from day - , then every days until ecmo day , ecmo weaning, or death, whichever occurred first. ecmo-related compli cations and organ dysfunction included major bleeding, blood-cell transfusions, massive haemolysis, ecmo-circuit change, severe thrombocytopenia (< × cells per l, occurring during the first study profile for patients included in this study, and their outcomes at july , . icu=intensive care unit. ecmo=extracorporeal membrane oxygenation. days of ecmo), stroke, renal replacement therapy, proven pulmonary embolism, pneumothorax, ventilatorasso ciated pneumonia, bacter aemia, and cardiac arrest. major bleeding was defined as requiring two or more units of packed red blood cells due to an obvious haemorrhagic event, necessitating a surgical or interventional pro cedure, an intracerebral haemorrhage, or a bleed causing a fatal outcome, while massive haemolysis was defined as plasma-free haemoglobin of more than mg/l associated with clinical signs of haemolysis. patient outcomes comprised the following endpoints: on ecmo, in the icu and weaned off ecmo, alive and out of icu, or died on days , , , , , , and after ecmo implantation. time spent in each state was calculated for the whole population of patients, with right-censoring of patients who did not reach the final absorbing state at later timepoints (day , , or ). other outcomes comprised icu and ecmo-related complications. patient characteristics are expressed as n (%) for categorical variables, mean (sd) for continuous variables, or median (iqr), as appropriate. to better describe patients' trajectories in the icu over time, a multi-state model chronic respiratory disease, copd, or asthma ( %) ( %) time from first symptoms to icu admission, days ( - ) ( - ) ( - ) ( - ) time from first symptoms to intubation, days ( - ) ( - ) ( - ) ( - ) time from intubation to ecmo, days ( - ) ( - ) ( - ) ( - ) states: in the icu and weaned off ecmo and alive and out of the icu. because patients could die at any time during follow-up, either in the icu or after discharge, the died state is the only final absorbing state (the final state that a patient can enter that once entered cannot be left). in this four-state model (appendix p ), each box represents a state and each arrow represents possible transitions from one state to another. after assessing patient status, participants who did not reach the final absorbing state were right-censored at the end of the observation period (july , ). a cox model stratified on each possible transition was fitted to estimate transition (from one state to another) and state occupation (for each of the four states) probabilities over time; the percentages of patients occupying each possible state were represented simultaneously over time with a stacked probability plot and reported with their % ci on days , , , , , , and post-ecmo initiation. another figure (appendix p ) individually displays all possible transition probabilities from one state to another over time. mean state occupation times (ie, the expected length of stay in each possible state of the multi-state model) was also reported at the same timepoints. finally, median on-ecmo time and length of icu stay were established. all the analyses were computed at a two-sided α level of % with r software, version . . . there was no funding source for this study. the corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. among the consecutive patients ( figure ) data are median (iqr) or n (%). ecmo=extracorporeal membrane oxygenation. icu=intensive care unit. pao /fio =ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen. paco =partial pressure of arterial carbon dioxide. resp=respiratory extracorporeal membrane oxygenation survival prediction. sao =arterial oxygen saturation. sofa=sequential organ-function assessment. copd=chronic obstructive pulmonary disorder. *of the patients discharged from the icu, on july , , were still hospitalised or in a rehabilitation centre and returned home. †of the five patients still in the icu, on july , , one remained on ecmo. ‡patients missing data. data missing for - patients, except for lymphocytes (n= ). §defined as haematological malignancies, active solid tumour, or having received specific anti-tumour treatment within year, solid-organ transplant or infected with hiv, long-term corticosteroids, or immunosuppressants. ¶defined as plateau pressure minus positive end-expiratory pressure. ||mechanical power (j/min)= · × tidal volume × respiratory rate × (peak pressure - / × driving pressure). if not specified, peak pressure was considered equal to plateau pressure. saps ii median score ). their pre-ecmo characteristics according to their endpoint state on july , , are reported in table . briefly, pre-ecmo rescue procedures consisted of prone-positioning (n= , %), continuous neuromuscular blockers (n= , %), and nitric oxide (n= , %). median peep was (iqr - ) cm h o, driving pressure was ( ) ( ) ( ) ( ) ( ) ( ) cm h o, and mechanical power was · ( · - · ) j/min. at cannulation, the median pao /fio was (iqr - ) mm hg and paco was ( - ) mm hg. for comparison, detailed characteristics of patients with covid- in our cohort and in the eolia trial group are reported in the appendix (pp - ). femoral-jugular cannulas were inserted in ( %) patients, mostly with a large ( fr) drainage cannula, a median (iqr - ) days after endotracheal intubation. the mert brought ( %) patients from non-ecmo centres. ecmo support successfully lowered tidal volume, respiratory rate, and plateau pressure during the h following its initiation: median · (iqr · - · ) ml/kg for tidal volume, ( - breaths per min for respiratory rate), and ( ) ( ) ( ) ( ) cm h o for plateau pressure (table , appendix pp - ). consequently, the mechanical power delivered to the lungs dropped to · (iqr · - · ) j/min. arterial blood gases also normalised rapidly on ecmo (appendix pp [ ] [ ] . on ecmo, ( %) patients were prone-positioned, ( %) received continuous neuromuscular blockers, five ( %) nitric oxide, and ( %) high-dose corticosteroids (table ) . median activated partial thromboplastin time ratios rose progressively over days - on ecmo: · (iqr · - · ) on day , · ( · - · ) on day , and · ( · - · ) on day . on july , , median follow-up was (range - ) days. complete follow-up on days was available for patients post-ecmo implantation, -day herein, we describe a large case series of patients who received ecmo support for the most severe forms of covid- ards. they were treated in the paris-sorbonne university hospital network icus, comprising five intensive care units, which are experienced in managing ards and ecmo. ecmo indications were based on the eolia trial selection criteria with an upper age limit of years, and patients received highly standardised ecmo care and general icu care. granular information on patients' pre-ecmo characteristics, daily management, and outcomes were analysed. contrary to preliminary results from other studies that indicated dismal outcomes with - % mortality of patients who had covid- and were treated with ecmo, , the estimated % probability of day- mortality for our patients on ecmo was similar to those treated with ecmo in the eolia trial ( % at day ) or the large prospective lifegard registry ( % at day ). the pre-ecmo characteristics of our patients with covid- indicated great ards severity before ecmo support was initiated. their mean pao /fio ( [sd ] mm hg) was lower than for patients in the eolia ( [ ] mm hg) or lifegard ( [ ] mm hg) trials, while pre-ecmo respiratory system compliance, driving pressure, mechanical power, and other respiratory and ventilatory parameters were similar in all three studies. notably, our patients with covid- had lower respi ratory system compliance and higher driving pressure than previously reported for most patients with covid- receiving mechanical ventilation, , indicating extensive sars-cov- -induced alveolar damage. according to guidelines from and for the optimisation of care for the most severe ards forms, , % of our patients benefited from prone-positioning before ecmo (compared with % in eolia and only % in lifegard ). beyond providing adequate oxygenation, high bloodflow ecmo achieves a homogeneous ultraprotective ventilation strategy, most frequently using bilevelpositive airway pressure or airway pressure-release ventilation modes, with tight control of the driving pressure. , our patients' pre-ecmo median mechanical power reached · (iqr · - · ) j/min, although a higher mortality risk for patients with ards whose value exceeded · j/min has been suggested. following ecmo initiation, tidal volume, driving pressure, and respiratory rate were markedly reduced in our patients, resulting in a major decrease of the median mechanical power to · (iqr · - · ) j/min, as previously reported. in addition, ecmo prone-positioning, used for % of our patients with covid- (vs only % of patients treated with ecmo in the eolia trial), sofa score on ecmo day * ( ) ( ) ( ) ( ) ( ) ( ) ( ) sofa score on ecmo day † ( ) ( ) ( ) ( ) ( ) ( ) aptt have contributed to improving their outcomes. indeed, a retrospective series of patients with severe ards showed that on-ecmo prone-positioning obtained higher ecmo weaning and survival rates. an autopsy-based histological analysis of the pulmonary vessels of patients with covid- showed widespread thrombosis with microangiopathy, with alveolar capillary microthrombi being nine times more frequent in patients with covid- than in those with influenza. consistent with other series, , , , we also observed an unusually high on-ecmo rate of proven pulmonary embolism ( %), an event not reported for the patients treated with ecmo in the eolia trial. those thromboembolic events occurred, despite an early increase of our anticoagulation target for patients with covid- receiving venovenous ecmo support, suggesting that other strategies, beyond systemic anti coagulation, are warranted to care for sars-cov- induced lung endothelial injuries. it should also be noted that haemorrhagic stroke occurred in % of our patients, which was more frequent than in the eolia trial ( %). the higher anticoagulation regimen, and specific sars cov- -associated vasculitis and critical illness associated microbleeds could explain this finding. however, the frequency of severe haemorrhagic events requiring transfusion in our study was similar to those of patients treated with ecmo in the eolia trial. compared with the eolia trial of patients with severe ards ( % bacterial and % viral pneumonia) treated with ecmo, has been proposed in patients with septic shock with severe myocardial dysfunction and decreased cardiac index, which was not the case in our patients. lastly, our antibiotic-treated ventilator-associated pneumonia rate was higher ( %) than for patients in the eolia trial ( %), and might reflect the longer mechanical ventilation or specific sars-cov- induced immunoparalysis. it should also be noted that few of our patients received high-dose corticosteroids. we acknowledge several limitations to our study. first, our results have to be considered preliminary, as some patients remained in the hospital and day- post-ecmo outcomes were not available for all patients. however, we used a time-to-event analysis, which allowed estimation of the probabilities of remaining on ecmo, ecmo weaning, icu discharge, or death over time, taking into account the fact that some patients' follow-up was censored. also, on july , , we carefully updated follow-up of all included patients to ensure the absence of informative censoring for unbiased estimations. second, our patients were treated in a high-volume ecmo university hospital network experienced in the care of the most severe forms of ards that might limit the generalisability of our observations. third, indication for ecmo and other selection and information biases might have existed due to the limited size of our cohort of patients. fourth, although the characteristics and outcomes of our ecmo-supported patients with covid- were similar to those reported in a series of ecmo-treated patients with severe ards before the pandemic, we were not able to compare our patients' outcomes to those of patients with covid- who were not ecmo-supported. fifth, only data for thrombo cytopenia occurring during the first days of ecmo were collected, which might have underestimated the actual rate of this complication. lastly, we did not collect data for patients' viral load and cannot ascertain the potential benefits of prone-positioning on ecmo, which might represent areas for future studies. in conclusion, the survival of ecmo-rescued very sick patients with covid- was similar to that reported in studies on ecmo support for severe ards published in the past few years. , should another covid- wave occur, ecmo should be considered at an early stage for patients developing profound respiratory failure, despite optimised conventional care, including prone-positioning. longer-term follow-up of these patients is also needed to evaluate the potential pulmonary, physical, and psychological sequelae of covid- . epidemiology, clinical course, and outcomes of critically ill adults with covid- in new york city: a prospective cohort study baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region extracorporeal membrane oxygenation for severe acute respiratory distress syndrome extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc bayesian analysis of a randomized clinical trial surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) extracorporeal life support organization coronavirus disease interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation 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contributor to covid- -associated coagulopathy: insights from a prospective single center cohort study abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia clinical features of patients infected with novel coronavirus in wuhan, china severe pulmonary embolism in covid- patients: a call for increased awareness high risk of thrombosis in patients with severe sars-cov- infection: a multicenter prospective cohort study mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome. an international multicenter prospective cohort prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: time for a randomized trial a new simplified acute physiology score (saps ii) based on a european/north american multicenter study the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/ failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. the respiratory extracorporeal membrane oxygenation survival prediction (resp) score ventilator-related causes of lung injury: the mechanical power physiologic analysis and clinical performance of the ventilatory ratio in acute respiratory distress syndrome tutorial in biostatistics: competing risks and multi-state models clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study covid- pneumonia: different respiratory treatments for different phenotypes? an official american thoracic society/european society of intensive care medicine/ society of critical care medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome formal guidelines: management of acute respiratory distress syndrome extracorporeal life support for adults with respiratory failure and related indications: a review driving pressure and survival in the acute respiratory distress syndrome mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid- confirmation of the high cumulative incidence of thrombotic complications in critically ill icu patients with covid- : an updated analysis pulmonary embolism in patients with covid- : awareness of an increased prevalence venoarterial extracorporeal membrane oxygenation support for refractory cardiovascular dysfunction during severe bacterial septic shock ms, gl, am, gv, dl, eb, ab, jc, pm, sn, pb, pl, ad, bg, jmc, mf, md, and ac were involved in data generation. ms, dh, and ac were involved in analysis of the data. ms, dh, and ac wrote the manuscript. all authors contributed to the revision, and read and approved the final version of the manuscript. ac takes responsibility for the integrity of the work as a whole, from inception to published article. ms reports lecture fees from getinge, drager, and xenios, outside of the submitted work. ad reports personal fees from medtronic, baxter, hamilton, and getinge; grants, personal fees, and non-financial support from philips; personal fees and non-financial support from fisher and paykel; grants from french ministry of health; grants and personal fees from respinor; grants and non-financial support from lungpacer, outside of the submitted work. jmc reports personal fees and nonfinancial support from drager, ge healthcare, sedana medical, baxter, amomed, fisher and paykel healthcare, orion, philips medical, and fresenius medical care, and non-financial support from lfb and bird corporation, outside of the submitted work. md received fees from lungpacer (expertise, lectures). ac reports grants from getinge, personal fees from getinge, baxter, and xenios, outside of the submitted work. gv reports grants and personal fees from biomérieux, grants from sos oxygène, and grants from janssen, outside of the submitted work. all other authors declare no competing interests. individual patient data reported in this article will be shared after de-identification (text, tables, figures, and appendices), beginning months and ending years after article publication, to researchers who provide a methodologically sound proposal and after approval of an internal scientific committee. proposals should be addressed to alain.combes@aphp.fr. to gain access, data requestors will need to sign a data access agreement. the data from this study are not currently part of any other international collection of data. key: cord- -j pu bv authors: byun, joung hun; kang, dong hoon; kim, jong woo; kim, sung hwan; moon, seong ho; yang, jun ho; jung, jae jun; cho, oh-hyun; hong, sun in; ryu, byung-han; park, hyun oh; choi, jun young; jang, in seok; kim, jong duk; lee, chung eun title: veno-arterial-venous extracorporeal membrane oxygenation in a critically ill patient with coronavirus disease date: - - journal: medicina (kaunas) doi: . /medicina sha: doc_id: cord_uid: j pu bv patients with cardiopulmonary failure may not be fully supported with typical configurations of extracorporeal membrane oxygenation (ecmo), either veno-arterial (va) or veno-venous (vv). veno-arterial-venous (vav)-ecmo is a technique used to support the cardiopulmonary systems during periods of inadequate gas exchange and perfusion. in the severe case of coronavirus disease (covid- ), which simultaneously affects the heart and lung, vav-ecmo may improve a patient’s recovery potential. we report the case of a -year-old woman with acute respiratory distress syndrome and circulatory failure following covid- , who was treated with vav-ecmo. in december , cases of pneumonia of an unknown etiology, now known as coronavirus disease (covid- ), spread rapidly around the world. clinical manifestations of covid- include myocarditis and acute respiratory distress syndrome (ards) in severe cases [ ] . to our knowledge, there are no definitive reports about extracorporeal membrane oxygenation (ecmo) mode for treating severe ards and left ventricular dysfunction due to covid- . such patients may be successfully treated with veno-arterial-venous-ecmo (vav-ecmo) by concurrently supporting both the heart and lungs. here, we report the case of patient with severe ards and left ventricular dysfunction due to covid- . we applied vav-ecmo to support both the heart and lungs. since then, the patient has been successfully weaned from both ecmo and ventilator and was discharged without complications. the patient was a -year-old woman whose condition deteriorated six days after confirmation of covid- . she had a past medical history of hypertension, an implanted pacemaker, and was on hydrocortisone for secondary adrenal insufficiency. multifocal pneumonia was detected on chest x-ray ( figure a ). the arterial blood gas analysis (abga) from the right radial artery revealed the following: ph, . ; paco , mmhg; and pao , mmhg at a ventilator setting of inspired oxygen fraction (fio ) %, tidal volume (tv) ml/kg, and positive end-expiratory pressure (peep) cmh o. transthoracic echocardiography (tte) revealed ejection fraction (ef) of %. tazobactam, hydrocortisone, hydroxychloroquine, lopinavir/ritonavir, and trimethoprim/sulfamethoxazole were administered concurrently. however, after five days, at a ventilator setting of fio %, tv ml/kg, peep cmh o, the patient's pao /fio deteriorated to , peak inspiratory pressure (pip) increased to mmhg, and lung infiltration worsened ( figure b ). despite administration of norepinephrine, the patient's hemodynamics was unstable, oliguria developed, and tte revealed an ef of %. in this situation, once the prone position was considered, since this patient showed a sharp drop in arterial pressure ( / mmhg) and bradycardia ( /min) when the position was changed, we decided to apply vav-ecmo since we believed that protecting the lungs and ensuring optimal perfusion to other organs were necessary. medicina , , of the patient was a -year-old woman whose condition deteriorated six days after confirmation of covid- . she had a past medical history of hypertension, an implanted pacemaker, and was on hydrocortisone for secondary adrenal insufficiency. multifocal pneumonia was detected on chest xray ( figure a ). the arterial blood gas analysis (abga) from the right radial artery revealed the following: ph, . ; paco , mmhg; and pao , mmhg at a ventilator setting of inspired oxygen fraction (fio ) %, tidal volume (tv) ml/kg, and positive end-expiratory pressure (peep) cmh o. transthoracic echocardiography (tte) revealed ejection fraction (ef) of %. tazobactam, hydrocortisone, hydroxychloroquine, lopinavir/ritonavir, and trimethoprim/sulfamethoxazole were administered concurrently. however, after five days, at a ventilator setting of fio %, tv ml/kg, peep cmh o, the patient's pao /fio deteriorated to , peak inspiratory pressure (pip) increased to mmhg, and lung infiltration worsened ( figure b ). despite administration of norepinephrine, the patient's hemodynamics was unstable, oliguria developed, and tte revealed an ef of %. in this situation, once the prone position was considered, since this patient showed a sharp drop in arterial pressure ( / mmhg) and bradycardia ( /min) when the position was changed, we decided to apply vav-ecmo since we believed that protecting the lungs and ensuring optimal perfusion to other organs were necessary. we inserted a -french gauge (fr) drainage cannula (edwards lifescience llc, irvine, ca, usa) via left common femoral vein, a -fr venous return cannula via the right common femoral vein, and an -fr arterial return cannula (edwards lifescience llc, irvine, ca, usa) via the right femoral artery. the divided return flow was monitored using an ultrasonic flow sensor (elsa, transonic systems, ithaca, ny, usa) and controlled by partially clamping the venous return cannula. we inserted a -french gauge (fr) drainage cannula (edwards lifescience llc, irvine, ca, usa) via left common femoral vein, a -fr venous return cannula via the right common femoral vein, and an -fr arterial return cannula (edwards lifescience llc, irvine, ca, usa) via the right femoral artery. the divided return flow was monitored using an ultrasonic flow sensor (elsa, transonic systems, ithaca, ny, usa) and controlled by partially clamping the venous return cannula. the arterial return flow was maintained at about - % of the cardiac output, and the venous return flow was maintained at about - % of the cardiac output. the patient's pao /fio was improved to with a ventilator setting of fio %, tv ml/kg, and peep cmh o, and pip remained at - cmh o. the patient's hemodynamics was stabilized without norepinephrine. the lung infiltration was the most exacerbated on the second day after initiating vav-ecmo ( figure c ). on the tenth day of vav-ecmo support, chest radiography ( figure d ) showed improvement. there was also a decrease in pronounced levels of troponin i and lactate days after ecmo treatment (table ) . we were able to wean her from vav-ecmo according to the vav-ecmo weaning protocol defined by our department (figure ). we performed ventricular setting during days after ecmo treatment (table ) . a percutaneous dilatational tracheostomy was performed, and the patient was weaned off the ventilator support six days after ecmo removal. figure e shows chest radiograph after removing the ventilator support. the arterial return flow was maintained at about - % of the cardiac output, and the venous return flow was maintained at about - % of the cardiac output. the patient's pao /fio was improved to with a ventilator setting of fio %, tv ml/kg, and peep cmh o, and pip remained at - cmh o. the patient's hemodynamics was stabilized without norepinephrine. the lung infiltration was the most exacerbated on the second day after initiating vav-ecmo ( figure c ). on the tenth day of vav-ecmo support, chest radiography ( figure d ) showed improvement. there was also a decrease in pronounced levels of troponin i and lactate days after ecmo treatment (table ) . we were able to wean her from vav-ecmo according to the vav-ecmo weaning protocol defined by our department (figure ). we performed ventricular setting during days after ecmo treatment (table ) . a percutaneous dilatational tracheostomy was performed, and the patient was weaned off the ventilator support six days after ecmo removal. figure e shows chest radiograph after removing the ventilator support. the patient was confirmed to be negative for the covid- virus three times by a real-time reverse transcription polymerase chain reaction (rrt-pcr) test. she was discharged without complications. we used hydrocortisone for about three weeks during ecmo operation from the hospitalization period. after that, we stopped it and patient was discharged after about eight weeks. the patient was confirmed to be negative for the covid- virus three times by a real-time reverse transcription polymerase chain reaction (rrt-pcr) test. she was discharged without complications. we used hydrocortisone for about three weeks during ecmo operation from the hospitalization period. after that, we stopped it and patient was discharged after about eight weeks. in december , cases of pneumonia of an unknown etiology, now known as covid- , were reported in wuhan, hubei province, china [ ] . since then, covid- has spread rapidly around the world, and the world health organization (who) has declared it a global pandemic. huang et al. presented a list of clinical manifestations, including fever, cough, and dyspnea, as well as radiographic evidence of pneumonia and organ dysfunction in severe cases [ ] . in a study of patients from two hospitals in wuhan, china, among the fatal cases, patients ( %) died of respiratory failure, ( %) with myocardial damage died of circulatory failure, and ( %) died of both [ ] . although definitive treatment guidelines are yet to be determined, the who has assembled a set of interim guidelines which recommend applying veno-venous (vv)-ecmo to patients with covid- -related ards [ ] . it is also believed that there is a need to respond quickly to circulatory failure. we think the initial indicators of circulatory failure are easy to miss, and irreversible organ damage is likely to occur. if, in a situation where respiratory failure is more severe and circulatory failure is thought to be modifiable by medications (inotropic agents), clinicians may consider applying vv-ecmo. if circulatory failure is more severe, many clinicians may consider applying veno-arterial (va)-ecmo with mechanical ventilator care. however, depending on the patient's clinical situation, optimal circulatory support or pulmonary protection may not be sufficiently achieved because these are combined in a series of clinical situations. according to extracorporeal life support organization (elso) guidelines, the application of vv-ecmo is suggested when the risk of mortality is % or greater. in terms of respiratory medicine, an % mortality risk is associated with a pao /fio < on fio > % and/or a murray score of - . the application of va-ecmo is indicated when inadequate tissue perfusion has manifested as hypotension and low cardiac output despite adequate intravascular volume [ ] . bartlett et al. [ ] reported ecmo is considered when the situation presenting pao /fio < lasts longer than h. our patient suffered from pao /fio < on fio % for h and had a murray score of . . the patient developed oliguria and her bp decreased below / mmhg despite the administration of norepinephrine. if only veno-arterial (va)-ecmo was applied, differential hypoxia, which is the severe complication of va-ecmo, might occur due to poor function of the lungs and desaturated blood from the left ventricle could cause cerebral and myocardial hypoxia [ ] . one of the major challenges is to decide on how to treat the injured lungs to keep alive and to promote the healing. the potential options range from complete lung rest [ ] . if vv-ecmo was applied alone, it would not provide direct hemodynamic support. in this regard, vav-ecmo primarily protects the lung and other organs, which can contribute to improving the patient's recovery. there are several opinions on how to approach the treatment of the novel covid- , and a definitive recommendation needs to be established in the future. in the interim, although not a definitive solution, we believe that vav-ecmo may be appropriate for treating severe cases of covid- . epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study clinical features of patients infected with novel coronavirus in clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china clinical management of severe acute respiratory infection when novel coronavirus ( -ncov) infection is suspected: interim guidance elso guidelines for cardiopulmonary extracorporeal life support initial elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure application of veno-arterial-venous extracorporeal membrane oxygenation on differential hypoxia extracorporeal membrane oxygenation for respiratory failure this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license we thank our patient who gave written informed consent in accordance with the declaration of helsinki. the protocol was approved by the ethics committee of gyeongsang national university hospital (irb no. - - ). the authors declare no conflict of interest. key: cord- -imrjlhia authors: reeb, j.; olland, a.; renaud, s.; kindo, m.; santelmo, n.; massard, g.; falcoz, p.-e. title: principi e indicazioni dell’assistenza circolatoria e respiratoria extracorporea in chirurgia toracica date: - - journal: emc - tecniche chirurgiche torace doi: . /s - ( ) - sha: doc_id: cord_uid: imrjlhia in origine, l’extracorporeal membrane oxygenation (ecmo) era una tecnica di assistenza respiratoria che utilizzava uno scambiatore gassoso a membrana. per estensione, l’ecmo è diventata una tecnica respiratoria e cardiopolmonare utilizzata in caso di deficit respiratorio e/o cardiaco nell’attesa della restaurazione della funzione deficitaria o di un eventuale trapianto. il supporto emodinamico può essere parziale o totale. gli accessi vascolari possono essere periferici o centrali. questo tipo di assistenza utilizza il concetto di circolazione extracorporea (cec) sanguigna che in epoca moderna si è estesa con l’utilizzo di polmoni artificiali a membrana. il circuito di base è semplice e comprende una pompa, un ossigenatore (che permette al sangue di caricarsi di o e di eliminare co ) e delle vie d’accesso (una di drenaggio e una di reinfusione). la sua attuazione è facile, veloce e può essere avviata al letto del malato. il miglioramento delle attrezzature, una migliore conoscenza delle tecniche e delle indicazioni, e le politiche di salute pubblica hanno reso popolare questa tecnica. alcuni centri di chirurgia toracica la utilizzano di routine come assistenza alla realizzazione di un intervento terapeutico (soprattutto trapianto) assieme a team di rianimazione per il trattamento della sindrome da distress respiratorio acuto. nel quadro della malattia polmonare dell’adulto, l’idea principale è quella di sviluppare il concetto di strategia minimalista con l’uso di una cec adiuvante parziale – più che sostitutiva totale – che permetterebbe il recupero metabolico ad integrum del paziente. nei prossimi anni, i progressi della tecnologia e dell’ingegneria così come le conoscenze approfondite permetteranno il miglioramento della prognosi dei pazienti colpiti da deficit respiratorio sotto assistenza meccanica. i - principi e indicazioni dell'assistenza circolatoria e respiratoria extracorporea in chirurgia toracica j. reeb alcuni centri di chirurgia toracica la utilizzano di routine come assistenza alla realizzazione di un intervento terapeutico (soprattutto trapianto) assieme a team di rianimazione per il trattamento della sindrome da distress respiratorio acuto. nel quadro della malattia polmonare dell'adulto, l'idea principale è quella di sviluppare il concetto di strategia minimalista con l'uso di una cec adiuvante parziale -più che sostitutiva totale -che permetterebbe il recupero metabolico ad integrum del paziente. nei prossimi anni, i progressi della tecnologia e dell'ingegneria così come le conoscenze approfondite permetteranno il miglioramento della prognosi dei pazienti colpiti da deficit respiratorio sotto assistenza meccanica. © alla sua origine, l'extracorporeal membrane oxygenation (ecmo) era una tecnica di assistenza respiratoria meccanica che utilizzava uno scambiatore gassoso a membrana. per estensione, l'ecmo è diventata una tecnica di assistenza respiratoria e cardiorespiratoria utilizzata nei casi di insufficienza polmonare e/o cardiaca. l'obiettivo di questa tecnica di assistenza è quello di sostituire l'apparato deficitario fino a: • la sua riabilitazione (bridge to recovery); • il trapianto (bridge to transplantion); • l'istituzione di una tecnica di assistenza meccanica a lungo termine (bridge to bridge). l'ecmo è tra le più semplici tecniche di assistenza circolatoria meccanica. impiantata tramite accessi vascolari periferici o centrali, questa tecnica di assistenza utilizza il concetto di circolazione extracorporea (cec) di sangue ossigenato e decarbossilato. il circuito dell'ecmo differisce da quello di una normale cec per l'assenza di serbatoio di cardiotomia. questo circuito comprende una pompa, una membrana che assicura la funzione di ematosi (ossigenazione del sangue con [o ] e la clearance dell'anidride carbonica [co ] sanguigna), insieme a delle vie d'accesso (cannule e linee di drenaggio o reimmissione). dal punto di vista della terminologia, il termine extracorporeal life support (ecls) dovrebbe essere riservato alle indicazioni cardiocircolatorie. l'ecls richiede un accesso venoarterioso (va) e permette una sostituzione cardiaca e polmonare. il termine di ecmo dovrebbe essere riservato alle assistenze respiratorie. gli accessi vascolari dell'ecmo sono venovenosi (vv), va, o arterovenosi (av). esistono altre denominazioni: extracorporeal co removal (ecco r), extracorporeal lung assist (ecla), e assistenza respiratoria extracorporea (arec) (fig. ). l'obiettivo e il razionale di questo trattamento sono due: • presentare le basi tecniche e concettuali dell'assistenza meccanica proprie alla gestione dell'apparecchio respiratorio; • sostenere queste basi con gli ultimi dati della letteratura in modo da esercitare l'assistenza meccanica in chirurgia toracica secondo una medicina basata sulle prove. l'area moderna dell'ecmo proviene da conoscenze ed esperienze acquisite in cec, così come da innovazioni provenienti dall'ingegneria meccanica. si sono succedute nel tempo tre generazioni di ossigenatore: • l'ossigenatore a bolla, di cui il primo datato [ ] [ ] [ ] ; • l'ossigenatore a membrana con fogli di polietilene [ ] ; • e, infine, l'ossigenatore a membrana in dimetilpolisilossano, sviluppato a partire dal [ , ] . questo ossigenatore fu progettato da kammermeyer. questo ha permesso il trasferimento di gas dieci volte più velocemente e la purificazione extracorporea di co . kolobow e bartlett migliorarono questa membrana in modo da ottenere durate di assistenza meccanica maggiori compatibili con un utilizzo al di fuori della sala operatoria [ ] . la prima esperienza positiva di assistenza respiratoria nell'adulto è stata descritta da hill nel . si trattava di un'ecmo va [ ] . nel , fu condotto uno studio multicentrico in seguito ai successivi casi positivi di ecmo va. questo studio multicentrico fu tuttavia interrotto davanti alle messa in evidenza di una mortalità significativa ( %) per complicanze emorragiche gravi [ ] . il mantenimento e infine l'entusiasmo dell'ecmo sono derivati da risultati positivi, in questa stessa epoca, dell'ecmo in neonatalogia. infatti, i neonati sotto arec avevano una sopravvivenza superiore al % [ ] . la prova del concetto dell'ecmo vv (ematosi extracorporea, persistenza del flusso sanguigno polmonare, riposo parziale dei polmoni, sopravvivenza) era stabile. i primi risultati positivi di assistenza respiratoria vv negli adulti sono stati pubblicati nel (quasi il % di sopravvivenza) [ ] . l'assistenza emodinamica si è sviluppata più tardivamente, principalmente grazie alla comparsa delle pompe centrifughe. successivamente, sotto l'influenza dei principali centri di trapianto polmonare, l'ecmo è entrata nell'arsenale terapeutico del chirurgo toracico. il primo ecmo impiantato nel contesto di un trapianto di polmone è stato descritto nel [ ] . È attraverso lo sviluppo e il crescente successo del trapianto di polmone che l'arec si è diffusa come supporto intra-o perichirurgico [ ] [ ] [ ] [ ] [ ] . a partire dagli anni , l'ecmo è di utilizzo crescente. il miglioramento del materiale a disposizione, i risultati favorevoli dello studio cesar e le politiche di sanità pubblica (lotta contro la pandemia di influenza a h /n nel , il trattamento dei casi di sindrome respiratoria acuta severa [sars] da coronavirus nel ) ha partecipato alla perpetuazione e all'estensione di questa tecnica [ ] [ ] [ ] . le caratteristiche delle tecniche di arec sono presentate nella tabella . il sangue venoso viene scaricato in un serbatoio (bladder box delle pompe occlusive) e poi, dopo il passaggio dal polmone artificiale, viene reinfuso nel sistema arterioso del paziente. il flusso di sangue è fornito da una pompa. in caso di accesso periferico, la cannula di drenaggio è piazzata nella vena giugulare interna o nella vena femorale. in questa configurazione, l'estremità distale della cannula deve essere il più vicino possibile all'atrio destro per ottimizzare il flusso di drenaggio e prevenire il fenomeno del collasso venoso sulla cannula. in caso di incannulamento centrale, l'estremità della cannula di drenaggio è preferibilmente piazzata nel segmento distale della vena cava inferiore attraverso l'atrio destro. l'accesso arterioso periferico utilizza preferenzialmente l'arteria femorale. la via ascellare può essere utilizzata in caso di arteriopatia degli arti inferiori, di potenziale difficoltà tecniche (obesità) o di paziente vigile. l'incannulazione dell'arteria carotide interna è utilizzata in pediatria. l'accesso arterioso centrale utilizza l'aorta toracica ascendente, discendente o l'arco aortico, a seconda del contesto patologico o chirurgico. ad esempio, si parla di un'ecmo va femoroascellare per un dispositivo che assicura un drenaggio venoso femorale e una reinfusione arteriosa ascellare. in questa configurazione, una parte del sangue venoso (effetto shunt) passa attraverso il polmone naturale. i gas del sangue, prelevati da un'arteria periferica, risultano dal mescolamento del sangue proveniente dal circuito extracorporeo e dal polmone nativo. l'ecmo va è raccomandata nelle indicazioni miste cardiache e respiratorie, ma anche per la protezione totale polmonare preservando il rapporto ventilazione/perfusione in maniera omogenea [ ] . l'ecmo va è fattibile in regime ambulatoriale. viene poi installata da unità mobili di assistenza circolatoria. l'ecmo va viene utilizzata nel prelievo di organi a cuore non battente. tecnica venovenosa (fig. ) il sangue venoso viene drenato attraverso la forza di gravità o per aspirazione regolata fino alla membrana di ossigenazione dove si effettuano gli scambi gassosi. l'idea di base della tecnica vv è di separare le funzioni polmonari di ossigenazione e di decarbossilazione. il sangue arricchito di o e depurato dalla co viene alimentato con l'aiuto di una pompa nel settore venoso del paziente. l'ecmo vv utilizza solo gli accessi periferici. le vie venose utilizzate sono principalmente la vena giugulare interna destra o la vena femorale. l'estremità distale della cannula di drenaggio è posizionata in prossimità dell'atrio destro per garantire un flusso di drenaggio sufficiente ed evitare un fenomeno di collasso della parete venosa sulla cannula di drenaggio. analogamente, l'estremità distale della cannula di reinfusione deve trovarsi prossima, o all'interno dell'atrio destro. pertanto, un inconveniente associato all'ecmo vv è il drenaggio del sangue ossigenato e decarbossilato infuso, mimando un circuito chiuso. questo fenomeno è chiamato "ricircolo". da un punto di vista "meccanico", sono consigliati un drenaggio del sistema della vena cava inferiore e una reinfusione nel sistema della vena cava superiore o nell'atrio destro. in termini di ossigenazione (compromesso tra il ricircolo e il flusso sanguigno attraverso la membrana), rich et al. hanno mostrato l'importanza del drenaggio nella femorale e della reinfusione nell'atrio destro tramite cannulazione della vena giugulare interna destra. una cannulazione in unico sito con un dispositivo a doppio lume presenta, a maggior ragione per il suo carattere meno invasivo, diversi vantaggi: la quasi assenza di ricircolo, il drenaggio sia del sistema della vena cava superiore che del sistema della vena cava inferiore, e la reinfusione in atrio destro attraverso la valvola tricuspide. la cannula a doppio lume si impianta nella giugulare interna destra, o nella vena succlavia e facilita l'autonomia del paziente sotto assistenza [ ] [ ] [ ] [ ] [ ] . l'ecmo vv è una tecnica di assistenza respiratoria. necessita di una funzione cardiaca normale e consente di effettuare una ventilazione protettiva diminuendo la distensione alveolare [ , ] . in questa situazione, il calo della ventilazione e la persistenza del normale flusso sanguigno portano alla creazione di uno shunt le cui conseguenze sono ancora poco chiare. la clearance della co dipende dal flusso di gas in contatto con la membrana di scambio gassoso. questo flusso di gas è chiamato anche "flusso di gas fresco" (fgf). maggiore è il fgf, più la decarbossilazione viene aumentata. la decarbossilazione è indipendente dal flusso di sangue della cec. teoricamente, poiché la decarbossilazione va da a ml/min, è possibile effettuare la clearance di tutta la co prodotta metabolicamente con un flusso di sangue nella cec da , a l/min ( l di sangue venoso con una pressione venosa di co principi e indicazioni dell'assistenza circolatoria e respiratoria extracorporea in chirurgia toracica a b figura . extracorporeal membrane oxygenation venovenosa (a) femorogiugulare interna destra (b) giugulare interna destra con cannula a doppio lume. [pvco ] mmhg ed un ph di , contiene circa ml di co ). in pratica, con le tecnologie attuali, la clearance completa del co prodotto metabolicamente richiede flussi di sangue compresi tra e l/min [ , ] . l'apporto di o dal polmone artificiale è direttamente dipendente dal flusso di sangue nella cec. il flusso sanguigno nella cec dipende principalmente dal flusso del circuito di cec ma anche dalla gittata cardiaca, dal tasso di emoglobina, e dalla saturazione arteriosa di o (sao ). il flusso di gas necessario per l'ossigenazione del sangue drenato dal polmone artificiale può essere molto basso. ad esempio, per una sao del % (con un'ecmo che circola a l/min, con un tasso di emoglobina di puro attraverso la membrana di ossigenazione per ottenere una sao del %. il flusso di sangue extracorporeo è fondamentale per l'ossigenazione artificiale, non per il fgf [ ] . nell'ecmo vv, il polmone artificiale è in serie coi polmoni nativi. esiste un effetto shunt tra polmone a monte e polmoni nativi a valle. il miglioramento della pressione arteriosa di ossigeno (pao ) è legato all'aumento della sao del sangue rilasciato agli organi nobili (cervello, cuore, polmoni). esiste, inoltre, per l'aumento della pao del sangue dell'arteria polmonare, una riduzione della vasocostrizione polmonare ipossica. perciò, la tecnica vv permette apporti di ossigeno compatibili con la vita. in confronto, la tecnica va fornisce un'ossigenazione sistemica superiore perché il sangue ossigenato artificialmente è direttamente mescolato con il sangue arterioso. tuttavia, in questa tecnica in cui il polmone artificiale è in parallelo ai polmoni nativi, sono perfusi con una sao adeguata solo gli organi distali e non vi è alcuna perdita di vasocostrizione polmonare. quindi la tecnica va, attraverso un'ossigenazione minore degli organi vitali, è inferiore alla tecnica vv per l'arec [ , ] . le caratteristiche delle cec va e vv sono confrontate nella tabella . il sistema novalung ® è un'arec av senza pompa [ ] . si tratta di una ventilazione extracorporea. il circuito esterno è massivamente ridotto per ridurre al minimo l'emodiluizione e le resistenze. la cannulazione periferica preferita è quella femorofemorale. questa può interessare anche i vasi succlavi, giugulari o carotidei. l'arec av può essere eseguita in un paziente vigile. in questa configurazione, l'ossigenatore è interposto sul flusso arterovenoso generato dal sistema circolatorio del paziente. il dispositivo novalung ® funziona quindi come uno shunt arterovenoso sinistro-destro tra l'arteria e la vena periferica. dal al % della gittata cardiaca è interessato dallo shunt. ciò comporta un aumento compensatorio della gittata cardiaca. l'incannulamento centrale del novalung ® viene utilizzato in caso di grave ipertensione arteriosa polmonare, complicata o no da insufficienza cardiaca destra. si parla di ecmo arteria polmonare-atrio sinistro (ap-as). questo dispositivo costituisce una settostomia di ossigenazione tramite shunt parziale destro/sinistro. in questa configurazione, la cannula di drenaggio viene posta nell'arteria polmonare. il sangue oltrepassa quindi la membrana di scambio gassoso e viene restituito nell'atrio sinistro. questo shunt ha quindi il vantaggio emodinamico della diminuzione del post-carico cardiaco destro e il vantaggio respiratorio della decarbossilazione [ ] . l'assistenza arterovenosa senza pompa novalung ® permette di caricare o e di scaricare co . la decarbossilazione può rappresentare quasi tutta la co prodotta (circa il %). l'impatto sull'ossigenazione è limitato dal flusso di sangue attraverso la membrana polmone artificiale. in configurazione va, la superficie di interfaccia tra il flusso di sangue anterogrado, espulso dal ventricolo sinistro, e il flusso di sangue retrogrado, infuso dalla ecmo, non può superare l'arco aortico. in caso di insufficienza polmonare associata, ne consegue un'ossigenazione subottimale degli organi nobili e dell'emicorpo superiore (oggettivata da una misurazione della pao radiale a destra). perciò, è possibile aggiungere una cannula venosa di infusione effettuando un montaggio detto a y. questa seconda cannula di infusione è introdotta nella giugulare interna destra o nella femorale a seconda della topografia della cannula di drenaggio. analogamente, nella configurazione vv, può essere fornito un supporto emodinamico supplementare aggiungendo una cannula d'iniezione arteriosa. si parla di ecmo vav. questa configurazione ha il vantaggio di ottimizzare l'ossigenazione cerebrale, coronarica e polmonare garantendo un supporto emodinamico [ ] . la tecnica della dialisi respiratoria ha come obiettivo una clearance parziale del co . il razionale di questa tecnica è il miglioramento funzionale dei pazienti affetti da acidosi respiratoria con una clearance del % della produzione basale di co [ ] . vengono utilizzati tre dispositivi principali: hemolung ® respiratorio assist system, ila activve ® e hemodec decapsmart ® . tutti e tre i dispositivi utilizzano cateteri a doppio lume di calibri da piccoli a medi ( , f per il sistema hemolung ® , da a f per il sistema ila activve ® , e f per il sistema decapsmart ® ). questi cateteri possono essere impiantati nella giugulare interna, succlavia, o nella femorale. il circuito di cec comprende, per ciascun dispositivo, una linea di drenaggio che porta alla membrana di scambio gassoso (superficie di , m per il dispositivo hemolung ® ) in cui si verifica la decarbossilazione parziale. il sangue parzialmente decarbossilato viene restituito al sistema venoso del paziente attraverso la linea di reinfusione e ad una velocità imposta da una pompa. i dispositivi hemolung ® e ila activve ® presentano il vantaggio di utilizzare delle pompe centrifughe. il dispositivo decapsmart ® impiega una pompa a rotella per aumentare l'emolisi e l'attivazione delle piastrine. la velocità di perfusione varia da a ml/min spiegando l'impossibilità di garantire la funzione di ossigenazione tramite questi dispositivi di dialisi respiratoria. per quanto riguarda la decarbossilazione, tali flussi permettono di stimare la clearance di co da a ml/min [ ] . l'uso della dialisi respiratoria richiede l'uso di un'anticoagulazione con eparina; l'activated clotting time (act) mirato è compreso tra e secondi. di piccola taglia, questi dispositivi lasciano libera la regione cervicale del piaziente e permettono una buona mobilità dei pazienti vigili. vari studi, a bassa potenza, valutano questi dispositivi nella pratica clinica, dal , emc -tecniche chirurgiche -torace i - - con risultati incoraggianti. tuttavia, sembra che questi dispositivi non permettano di ridurre le complicanze emorragiche del supporto meccanico [ ] . attualmente, le pompe utilizzate sono essenzialmente di tipo centrifugo la cui caratteristica principale è la non-occlusività (vale a dire che continuano a funzionare in assenza di ritorno sanguigno adattato anche se non generano più un flusso). in tal modo, il flusso dipende non soltanto dalla velocità di rotazione, ma anche dalle pressioni di entrata-uscita e dalla dimensione delle cannule. le pompe centrifughe utilizzano l'effetto vortice: è un rotore che gira creando il flusso e la portata; non escludono il rischio di emolisi e di pressione negativa [ ] . il flusso rilasciato è continuo. È vicino alla gittata cardiaca teorica in caso di supporto circolatorio ed è situato tra e l/min in caso di assistenza respiratoria. a velocità di rotazione costante, ogni variazione della velocitàmisurata da un flussometro elettromagnetico o da un velocimetro doppler -deve essere interpretata come una variazione di pressione a valle o a monte del circuito. perciò, una diminuzione del flusso corrisponde ad una diminuzione del riempimento della pompa centrifuga (diminuzione del precarico dovuto a ipovolemia, miglioramento del riempimento del ventricolo assistito o ostacolo sulla linea di drenaggio) o un aumento della resistenza all'infusione (aumento del postcarico per aumento delle resistenze vascolari o ostacolo sulla linea di reinfusione). esiste quindi un'autoregolazione che facilita la gestione e il monitoraggio dell'assistenza meccanica. sono presenti sul mercato quattro pompe: biopump ® , rotaflow ® , centrimag ® , e revolution ® . utilizzi prolungati sono possibili sia nell'animale che nell'uomo [ , ] . la natura pulsata proposta dalla pompa deltastream ® non ha mostrato alcun vantaggio clinico. si tratta del componente che comprende la membrana di scambio gassoso più comunemente chiamata membrana di ossigenazione. l'ossigenatore ha la funzione di ossigenazione e decarbossilazione. la membrana di scambio gassoso fornisce un'interfaccia tra il compartimento sanguigno e quello gassoso permettendo un minor traumatismo degli elementi del sangue e un rischio di embolia gassosa quasi nullo. a causa della resistenza al flusso che generano, gli ossigenatori sono posti a valle della pompa. gli scambi gassosi avvengono per diffusione. tra gli ossigenatori a membrana, quelli in polimetilpentene presentano come vantaggio una pulizia rapida, un coefficiente di diffusione elevato, e una durata di vita di più settimane (impermeabilizzazione con silicone che riduce la fuga plasmatica) [ ] . il materiale utilizzato per la membrana è cruciale per la biocompatibilità e per la qualità degli scambi gassosi [ ] . la membrana separa un compartimento sanguigno da a m di spessore e un compartimento gassoso. la depurazione dalla co è indipendente dal flusso sanguigno e dallo spessore della membrana, ma dipende dal fgf (flusso di gas fresco), dal gradiente di diffusione, dalla superficie della membrana, e dalla depressione applicata all'uscita dal circuito gassoso [ ] . l'ossigenazione è indipendente dal fgf ma varia a seconda della concentrazione di ossigeno erogata nella miscela di gas (fdo ) e delle caratteristiche della membrana. l'apporto di o al paziente dipende dal flusso della pompa [ , ] . la composizione dei gas che entrano nelle membrane regola la composizione del gas alveolare. facoltativo, può essere integrato sul circuito per modulare la temperatura. gli scambi termici avvengono tramite conduzione a partire dai gradienti termici tra l'ambiente sanguigno e il reticolo termostatico. le cannule sono profilate, adatte all'uso periferico, con una parete fine, resistente e supportata da una spira metallica che impedisce torsioni e inginocchiamenti. le loro dimensioni dipendono dai vasi cateterizzati. la scelta del diametro della cannula di drenaggio è uno dei fattori che determinano il flusso sanguigno che arriva alla pompa e da lì il livello di supporto extracorporeo. come minimo, la cannula deve sopportare un flusso sufficiente per un'assistenza che generi una depressione tramite gravità di cmh o. sembra interessante in questo contesto usare delle cannule autoespansive (smart canula ® ) che permettono di ottenere dei flussi di drenaggio superiori a quelli delle cannule classiche e che evitano il collasso venoso. in generale, qualsiasi cannula venosa, sia di drenaggio che di infusione, deve avere dimensioni sufficienti a: la scelta del diametro della cannula arteriosa è meno importante. il flusso di assistenza deve essere ottimale mantenendo una pressione premembranosa inferiore a mmhg. l'uso di una cannula arteriosa di calibro troppo piccolo aumenta le forze di taglio e la turbolenza del flusso, conducendo a un'emolisi. il limite superiore è correlato al diametro del vaso ricevente e all'ostruzione vascolare indotta dalla cannula. generalmente, il diametro della cannula arteriosa dovrebbe consentire di ottenere la gittata cardiaca teorica del paziente. si tratta di un circuito sottoposto a un trattamento superficiale per migliorare la sua compatibilità, il cui scopo è quello di limitare il contatto del sangue con una superficie a rischio infiammatorio e trombotico [ ] . il trattamento superficiale più comune è la pre-eparinizzazione (heparin coated) la cui importanza sta nell'adesione selettiva di proteine plasmatiche grazie alla creazione di una membrana (sorta di interfaccia tra la parete e il sangue) che prevenga un'estensione dell'attivazione sanguigna. l'interesse di tali dispositivi è stato dimostrato nella cec standard ma non nel campo della ecmo. tuttavia, sembra legittimo usarli in questo contesto. permettono di diminuire le posologie di eparina e quindi di ridurre il rischio emorragico, così come la sindrome infiammatoria indotta dal circuito extracorporeo. la completa assenza di terapia con eparina, soprattutto per periodi prolungati di ecmo (più di h), deve bilanciare il rischio emorragico e il rischio trombotico. solo il posizionamento di un'ecmo in un contesto di traumi multipli (trauma cranico, ematoma retroperitoneale) sembra essere un'indicazione da ricordare. per ridurre il rischio di trombosi, conviene mantenere un flusso maggiore di , l/min e ricercare trombi nel circuito (ossigenatore) e nel paziente (camere cardiache) [ , ] . l'ergonomia attuale della tecnologia ecmo permette l'inizio dell'assistenza e/o il trasferimento ospedaliero del paziente in buone condizioni emodinamiche e respiratorie. sono possibili tutti i mezzi di trasporto a lunga distanza [ , ] (ambulanza, elicottero, aereo). tali trasferimenti richiedono un'organizzazione strutturata e un team di esperti. allo stesso modo la tecnologia ecmo è aumentata per mantenere il paziente vigile permettendogli di partecipare attivamente alla cura (fisioterapia), di spostarsi, e di mantenere un sufficiente grado di autonomia e di decisione. l'uso della cannula a doppio lume bicava, o il suo impianto tramite accesso sottoclaveare, è adatto al paziente sveglio [ , , ] . all'inizio utilizzata per indicazioni respiratorie che utilizzano l'ecmo vv, questa tecnica di ecmo vigile si estende a tutte le configurazioni dell'ecmo. il sistema ecmo compatto cardiohelp ® promuove anche la mobilità dei pazienti in assistenza respiratoria o circolatoria meccanica [ ] . epidemiologia l'esperienza dell'ecmo è basata su anni di riscontri e più di impianti segnalati. se nel tempo l'ecmo è rimasta focalizzata sulle indicazioni del deficit respiratorio del neonato, non è più così da dieci anni a questa parte. le indicazioni nell'adulto sono in rapido aumento, in particolare le indicazioni emodinamiche. il o gennaio , secondo il registro dell'extracorporeal life support organization, i tassi di sopravvivenza tra i neonati, i bambini sotto i anni e gli adulti erano rispettivamente il %, il % e il % sotto assistenza respiratoria, e il %, il % e il % sotto assistenza emodinamica. si presentano qui di seguito le indicazioni intrinseche alla chirurgia toracica e al supporto dell'apparato respiratorio. le indicazioni cardiogeniche non sono dettagliate. citiamo tra le indicazioni: lo shock cardiogeno (secondario o meno a un infarto del miocardio, post-cardiotomia o spontaneo), le miocarditi fulminanti, il ponte al trapianto cardiaco o all'inserzione di dispositivo di assistenza ventricolare sinistra e/o destra, così come la disfunzione primaria del trapianto cardiaco. l'uso di ecmo va in un paziente in arresto cardiaco o durante lo shock settico è soggetto a controversie (rispettivamente a causa della prognosi estremamente sfavorevole e della componente vasoplegica dello shock) [ ] . " punto importante l'ecmo vv è un'opzione terapeutica che deve essere considerata in tutte le situazioni a rischio di lesioni polmonari indotte dalla ventilazione. l'ards rappresenta la più grande indicazione dell'ecmo vv. fino ad oggi, l'unica strategia che ha dimostrato una riduzione della mortalità in ards è la strategia di ventilazione protettiva a basso volume (volume corrente = - ml/kg) e a basse pressioni (pressione di plateau < cmh o) [ ] . tuttavia, l'ecmo è una opzione terapeutica nei casi di ards severi refrattari a un trattamento medico ottimale e/o in caso di impossibilità di effettuare una ventilazione protettrice. l'ards grave è definita, secondo la classificazione di berlino, da un rapporto pao /frazione ispirata di ossigeno (fio )inferiore o uguale a mmhg [ ] . la scelta tra una tecnica vv e una va si effettua a seconda dello stato emodinamico del paziente, tenendo a mente che in questo contesto, un'instabilità circolatoria secondaria a un'ipossiemia e/o a un'acidosi respiratoria è facilmente corretta dall'apporto di sangue ossigenato e decarbossilato alle arterie coronarie. l'ecmo vv ha quindi, in questo caso, una migliore efficienza emodinamica dell'ecmo va. lo studio controllato cesar ha paragonato la ventilazione convenzionale a una gestione tramite ecmo. ne è risultata una significativa riduzione della mortalità e della morbilità a sei mesi nel gruppo ecmo rispetto al gruppo di ventilazione convenzionale ( % versus %; rischio relativo [rr] = , ; p = , ) [ ] . tuttavia, questi ottimi risultati devono essere ponderati per il fatto che il % dei pazienti nel gruppo di controllo non ha avuto una ventilazione protettiva, e solo il % dei pazienti del gruppo ecmo ha avuto bisogno di un tale dispositivo. quindi, la conclusione appropriata di questo studio è il vantaggio della gestione di questi pazienti in un centro di riferimento che dispone di ecmo [ , ] . l'aumento dell'ecmo nell'ards proviene anche dal suo uso durante le pandemie successive di influenza a h n . anche i governi, attraverso il loro supporto logistico, hanno contribuito alla conoscenza e alla diffusione di questa tecnica. i primi risultati dell'ecmo nell'ards associata all'influenza a h n sono stati pubblicati da dei ricercatori australiani e neozelandesi. questo studio, condotto su pazienti, presentava risultati eccellenti soprattutto con una sopravvivenza del %. tuttavia, sembra che la tecnica sia stata proposta a dei pazienti ultraselezionati (età media: anni [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ) [ ] . uno studio simile è stato condotto su una coorte francese e non ha mostrato benefici da parte dell'ecmo sulla sopravvivenza [ ] . È opportuno che siano condotti degli studi prospettici randomizzati per valutare l'ecmo nel trattamento dell'ards grave. sono soprattutto attesi i risultati dello studio ecmo to rescue lung injury in severe ards (eolia) (extracorporeal membrane oxygenation for severe acute respiratory distress syndrome) [ ] . sono stati sviluppati diversi punteggi predittivi di mortalità per ards; nessuno è tale da imporsi come riferimento. la prima ecmo riportata in letteratura nel contesto di un trapianto di polmone è datata [ ] . il ricorso alla ecmo, in questo contesto nosologico, può realizzarsi in tre fasi distinte: • prima del trapianto polmonare: ponte verso il trapianto di polmone; • durante il trapianto polmonare: supporto emodinamico e respiratorio intraoperatorio; • dopo il trapianto polmonare: gestione della disfunzione primaria dell'innesto polmonare (dpi). l'assistenza tecnica meccanica utilizzata dipende dal tipo di supporto necessario, dall'eziologia del compenso respiratorio, e dalla patologia iniziale del paziente. citiamo anche i particolari casi di assistenza meccanica in caso di ipertensione arteriosa polmonare primitiva (iap) severa e di prelievo d'organo da donatore a cuore non battente (dcnb). il primo successo dell'ecmo a ponte al trapianto polmonare è stato descritto nel durante un reimpianto per dpi [ ] . fino a poco tempo, l'uso dell'ecmo come ponte al trapianto polmonare era controverso a causa dei suoi deboli risultati [ ] . recenti studi, provenienti da centri esperti, hanno tuttavia descritto eccellenti risultati in termini di sopravvivenza, partecipando alla netta crescita di questa indicazione [ , ] . esistono diverse strategie di ponte al trapianto: ecmo vv, ecmo va, ecmo av, dialisi respiratoria, ecc. l'esperienza francese è stata riportata in uno studio retrospettivo realizzato in pazienti. i risultati, in intention to treat, di sopravvivenza a un anno e a due anni erano rispettivamente del , % e del , %. l'eziologia dell'insufficienza respiratoria ha una significativa influenza in questi risultati poiché, in questa serie, le sopravvivenze erano del % per la fibrosi polmonare e del % per la fibrosi cistica (p < , ) [ ] . tra le possibili strategie, sembra vantaggioso offrire ai pazienti idonei un'arec prioritariamente alla ventilazione meccanica oppure svezzare questi pazienti dalla ventilazione meccanica prioritariamente alla ecmo. questa strategia permetterebbe di liberarsi dai rischi di decondizionamento muscolare e di pneumopatia sotto ventilazione meccanica permettendo un'alimentazione orale, la realizzazione di una fisioterapia attiva, il mantenimento della mobilità e della comunicazione, e la possibilità di partecipazione alle prese di decisione [ , , [ ] [ ] [ ] [ ] [ ] . nel , uno studio ha confrontato cinque pazienti che avevano beneficiato di una strategia di ponte al trapianto polmonare tramite ecmo vigile a quattro pazienti che avevano avuto un ponte al trapianto polmonare tramite ecmo e ventilazione meccanica. l'intera coorte aveva una sopravvivenza del % a un anno, ma i pazienti trattati con arec senza intubazione avevano durate di ventilazione meccanica, di degenza in rianimazione, e di degenza ospedaliera significativamente inferiori a quelle dei pazienti intubati (p = , ). inoltre nessuno dei pazienti vigili presentava miopatie post-trapianto (contro tre nei pazienti intubati) [ ] . gattinoni e il suo team, in uno studio bicentrico su pazienti, ha concluso che i pazienti la cui lunghezza del ponte al trapianto di polmone era inferiore a giorni avevano una migliore sopravvivenza rispetto a quelli la cui durata era superiore (hazard ratio [hr] di , giorni di ponte al trapianto polmonare; intervallo di confidenza [ic] %, , - , ; p = , ). nello stesso studio, gli autori hanno messo in evidenza una morbilità inferiore nei pazienti vigili rispetto ai pazienti intubati [ ] . il supporto emodinamico e respiratorio in corso di trapianto polmonare può essere assicurato da una tecnica di cec convenzionale o da un'ecmo va. l'ecmo va è preferibilmente centrale, utilizzando gli stessi siti di cannulazione della cec standard. una particolare attenzione è posta all'impianto della cannula venosa nell'atrio destro per evitare embolie gassose. l'uso dell'ecmo vv come supporto respiratorio intraoperatorio isolato non è stata valutato; i centri esperti privilegiano una tecnica di assistenza respiratoria ed emodinamica. il razionale di questa gestione è triplo: • possibilità di assistenza circolatoria; • mantenimento di una pressione arteriosa polmonare sistolica peritrapianto inferiore a mmhg; • la prevenzione di lesioni polmonari per iperflusso arterioso polmonare; in particolare dopo impianto del primo polmone. la cec convenzionale costituisce la tecnica standard. questa tecnica sembra presentare tuttavia un rischio accresciuto di sanguinamento intra-e post-operatorio, di sindrome di risposta infiammatoria sistemica, e quindi di dpi. l'ecmo va non dispone né di serbatoio sanguigno né di linee di aspirazione. i suoi vantaggi rispetto alla cec convenzionale sono la necessità di dosi di eparina inferiori, una superficie di contatto minore, e la possibilità di essere mantenuta alla fine della procedura chirurgica. i risultati della letteratura per la scelta di una delle due tecniche sono, da poco, in favore dell'ecmo va. nel , un primo studio che confrontava sette pazienti assistiti da cec convenzionale con otto pazienti trattati con ecmo va femorofemorale oggettivava una durata della ventilazione meccanica e un tasso di trasfusione di globuli rossi nelle prime ore postoperatorie superiori nel gruppo ecmo. analogamente, la sopravvivenza a un anno dei pazienti assistiti con ecmo va era inferiore a quella dei pazienti che avevano ricevuto assistenza tramite cec convenzionale [ ] . al contrario, un confronto storico più recente, su una coorte di pazienti ( pazienti nel gruppo cec, pazienti nel gruppo ecmo va), e realizzato da un'équipe più esperta, ha evidenziato un tasso di trasfusione intraoperatoria e tassi di mortalità in ospedale, poi a tre, a nove e a mesi superiori nel gruppo cec rispetto al gruppo ecmo. l'uso della cec, secondo questo studio, aumenterebbe del , il rischio di decesso ospedaliero (odds ratio [or] = , ; ic % = , - ; p = , ) [ ] . questi primi dati, in favore dell'ecmo va, sono stati confermati dal programma di trapianto di polmone di toronto nel . in questo nuovo studio, pazienti trattati con ecmo va sono stati confrontati con pazienti accoppiati che avevano avuto una cec convenzionale. i pazienti trattati con un'ecmo va avevano avuto durate medie di ventilazione meccanica, di degenza in rianimazione, e di degenza ospedaliera inferiori a quelli assistiti dalla cec convenzionale. non c'era differenza nella sopravvivenza a giorni e a mesi tra i due gruppi [ ] . la dpi è la prima causa di decesso precoce dopo trapianto polmonare. l'ecmo è utilizzata per il trattamento delle dpi di grado refrattarie alla terapia medica ottimale [ , ] . questa è l'unica tecnica che permette un'ossigenazione e una decarbossilazione adeguate astenendosi dagli effetti deleteri di una ventilazione aggressiva e di un'ipossiemia persistente. tuttavia, l'efficacia dell'ecmo rimane controversa, a medio e lungo termine [ , ] . la situazione più favorevole per l'uso dell'ecmo si verifica quando la dpi apparirebbe immediatamente dopo il trapianto e l'ecmo avviata dirigendosi in sala operatoria o entro ore [ ] [ ] [ ] . in questa situazione precoce, sono stati riportati dei tassi di sopravvivenza dal all' % [ ] . sembra che la decisione di applicare un'ecmo debba essere presa al più tardi entro ore dopo la riperfusione e comunque non oltre il settimo giorno dopo il trapianto [ ] . nello studio di dahlberg, la mortalità a giorni era del % nei pazienti trattati con ecmo lo stesso giorno del trapianto e del % tra quelli per i quali l'ecmo era cominciata dopo ore [ ] . l'evoluzione degli scambi gassosi e del profilo emodinamico, l'età dei pazienti, il tipo di trapianto (polmone singolo o doppio), e l'assenza di svezzamento dopo un'ecmo di - giorni sembrano influenzare la prognosi vitale [ , , ] . il ricorso all'ecmo dopo il trapianto polmonare non sembra influire sulla qualità funzionale del trapianto a lungo termine. uno studio di confronto tra pazienti trapiantati che avevano ricevuto un'ecmo nella popolazione generale dei pazienti trapiantati dallo stesso team hanno dimostrato, in un anno post-trapianto, un volume espiratorio massimo/secondo (fev) equivalente tra i due gruppi ( % del fev teorico) [ ] . ipertensione arteriosa polmonare primitiva severa l'ecmo è un'opzione terapeutica in caso di scompenso di ipa complicato o no da deficit cardiaco destro. l'ecmo sembra particolarmente appropriata in questa indicazione quando la causa di scompenso è reversibile, il trattamento può essere migliorato, e viene iniziato un ponte al trapianto polmonare o cardiopolmonare [ ] . possono essere utilizzate tre tecniche di assistenza meccanica in caso di ipa: l'ecmo va ha la proprietà di superare la forte resistenza vascolare polmonare e di ridurre la pressione ventricolare destra [ , ] . l'ecmo vv, orientando il flusso di infusione della cannula a doppio lume verso la comunicazione interatriale, ha il vantaggio di costituire uno shunt destro-sinistro di ossigenazione diminuendo la pressione ventricolare destra [ ] . lo shunt senza pompa tra l'arteria polmonare e l'atrio sinistro tramite il sistema novalung ® ha la capacità di realizzare uno shunt destro-sinistro, migliorando l'ematosi e diminuendo il postcarico ventricolare destro. l'impianto del novalung ® , in questa configurazione, viene fatto in sala operatoria tramite sternotomia. l'impianto di un'ecmo va periferica, prima dell'induzione anestetica, può essere necessario nei pazienti instabili emodinamicamente. questa ecmo va può essere, se necessario, impiantata qualche giorno prima dell'ecmo ap-as per riabilitare altri organi deficitari e sincerarsi della buona decisione terapeutica (bridge to bridge). la scelta della cannula arteriosa polmonare sembra fondamentale per ottenere una pressione arteriosa polmonare inferiore a mmhg a l/min di flusso sanguigno. sembra che questa tecnica permetta una rapida stabilizzazione dei pazienti, anche in caso di shock cardiogeno iniziale. questa tecnica permette un'assistenza di diverse settimane ed è possibile in pazienti vigili. È stato anche dimostrato che questa tecnica permetterebbe un rimodellamento del ventricolo destro. ciò comporterebbe l'abbandono del trapianto cardiopolmonare a beneficio del trapianto polmonare isolato [ ] . per quanto riguarda le misure terapeutiche connesse con l'ecmo nella iap, sembra che in caso di ecmo come un ponte per il recupero, debbano essere ottimizzati i trattamenti medici. viceversa, quando l'ecmo viene utilizzata come ponte per il trapianto, sembra che le dosi di farmaci associati debbano essere diminuite in modo da orientare il flusso sanguigno verso il circuito extracorporeo e diminuire la pressione ventricolare destra [ ] . • nei pazienti con grave ipertensione arteriosa polmonare, la creazione di uno shunt destro/sinistro di ossigenazione è da privilegiare. • come ponte al trapianto polmonare dei pazienti colpiti da iap, l'ecmo ap-as sembra essere la migliore strategia da adottare. • in caso di ipa, la cinetica di gestione è: -ecmo va femorofemorale: riabilitazione degli organi deficitari bridge to bridge/bridge to decision; -ecmo ap-as senza pompa; -svezzamento progressivo dell'ecmo va, in sala operatoria se possibile, sennò in rianimazione; ponte al trapianto bipolmonare in un paziente vigile, e in assenza di trattamento medico diretto contro la iap. il prelievo di organi solidi nel dcnb si è sviluppato davanti alla necessità di aumentare il pool di trapianti. sono descritti due tipi di dcnb: il dcnb controllato (categorie e di maastricht) e il dcnb incontrollato (categoria di maastricht). l'ecmo va femorofemorale è utilizzata per la preservazione regionale normotermica degli organi addominali dei dnbc non controllati. in questo contesto, i polmoni sono esclusi dalla circolazione mediante un palloncino posizionato in aorta discendente e sono mantenuti in ipotermia attraverso una perfusione pleurica di perfadex ® a • c. si parla di conservazione bi-termica [ , ] . il primo trapianto di polmone che utilizzava un innesto di dcnb è datato [ ] . l'uso di innesti polmonari provenienti da dcnb controllati non altera né la sopravvivenza, né la percentuale di dpi rispetto ai donatori con morte cerebrale [ ] . allo stesso modo, l'uso di trapianti di polmone da dcnb non controllati è realizzabile senza aumentare la mortalità e il tasso di disfunzione cronica del trapianto [ , ] . l'uso della perfusione addominale normotermica permetterebbe una ripresa della fuzione più rapida, una dimunzione del tasso di dpi, una sopravvivenza più lunga dei trapianti renali, e anche un aumento del pool di trapianti epatici [ ] [ ] [ ] . in questo contesto, l'ecmo può avere luogo come supporto o emodinamico (contusione miocardica) ventilatorio (contusione polmonare, ferita tracheobronchiale, systemic inflammatory response syndrome). È in genere in questo contesto di traumi multipli che troviamo l'utilizzo di ecmo senza eparina per via di un maggiore rischio emorragico [ ] . la maggior parte dei casi di arec su singolo polmone sono casi clinici di ecmo per assistenza respiratoria intraoperatoria di chirurgia tumorale controlaterale, o dell'albero tracheobronchiale o anche di lesioni enfisematose. il primo successo dell'arec in un paziente che ha subito una pneumonectomia è riportato da dünser nel . si trattava di un paziente di anni trattato con ecmo per ards post-pneumonectomia su fistola tracheo-bronchiale [ ] . non vi è, a nostra conoscenza, una serie pubblicata di ecmo vv postpneumonectomia. la più grande serie riportata comprende sette pazienti, inclusi dopo una resezione polmonare. di questi sette pazienti, cinque erano stati trattati con pneumonectomia. tutti questi pazienti erano colpiti da ars severe refrattarie. tutti erano stati trattati con ecmo av novalung ® . tra questi pazienti, uno solo è deceduto, di insufficienza multiorgano [ ] . sono stati riportati in letteratura tre casi di intervento chirurgico di riduzione del volume (unilaterale o bilaterale) per i pazienti enfisematosi con grave ipercapnia. gli autori hanno concluso che l'uso di ecmo rendeva più facile la gestione intraoperatoria, e che così potevano essere allargate le indicazioni per questo tipo di pazienti [ ] . sono stati riportati casi successivi in letteratura. l'embolia polmonare è una buona indicazione del posizionamento di ecmo va in caso di shock cardiogeno, soprattutto se quest'ultimo persiste dopo embolectomia [ ] . tuttavia, sembra che la necessità di ecmo nel postoperatorio sia un fattore di rischio predittivo di decesso ospedaliero [ ] . l'indicazione dell'ecmo è molto più discutibile in caso di arresto cardiaco refrattario dove la cattiva prognosi del paziente sembra essere legata all'inefficacia delle manovre di rianimazione a causa dell'ostruzione dell'arteria polmonare [ ] . sono stati riportati dei rari casi nella letteratura riguardo al lavaggio alveolare sotto ecmo vv (o va) nel quadro delle proteinosi alveolari. la conclusione degli autori è che si tratti di una metodica semplice, efficace, adatta alla gestione di questa patologia. bisognerebbe piuttosto realizzare un lavaggio sequenziale bilaterale [ , ] . se la posa dell'ecmo richiede un team medico-chirurgico con conoscenza della tecnologia, non richiede per il suo posizionamento alcuna struttura specializzata. l'impianto può essere fatto al letto del paziente o in una vasta gamma di siti (sala operatoria, terapia intensiva, sala di cateterizzazione) [ ] . questa flessibilità di utilizzo è legata alla mobilità del sistema (circuito, batterie, bombole di gas) montato su un carrello, in modo da spostare il paziente assieme al suo supporto. accesso femorale arterioso o venoso l'accesso femorale nell'adulto è l'accesso più frequentemente utilizzato per via del diametro dei vasi, della facilità e della rapidità d'accesso [ ] . inoltre, in caso di impianto sotto massaggio cardiaco esterno, permette di proseguire le manovre di rianimazione. la principale complicanza associata all'accesso femorale resta l'ischemia a valle della cannula arteriosa. per la cannula venosa, è preferibile l'accesso dalla femorale destra nei pazienti di grandi dimensioni (≥ , m) per essere certi che l'estremità della cannula può essere posizionata nell'aggettamento della vena cava inferiore nell'atrio destro. l'accesso dell'arteria ascellare per la cannulazione arteriosa è stato descritto da navia et al. [ ] . questo accesso sembra interessante nel paziente con un'arteriopatia degli arti inferiori. infatti, data la ricca rete collaterale dell'arteria ascellare, il rischio di ischemia a valle sembra essere minimo. tuttavia, il suo posizionamento è tecnicamente più lungo dell'accesso femorale, cosa che non ne fa una pratica di scelta in urgenza. l'interposizione di una protesi tra la cannula e l'arteria è consigliata per ridurre le lesioni locali e l'arto superiore del paziente deve essere mantenuto in adduzione. inoltre, il sangue ossigenato che arriva attraverso il tronco arterioso brachiocefalico arricchisce il sangue espulso dal ventricolo sinistro, sangue che perfonde i vasi coronarici e cerebrali. questo può avere un significativo interesse in caso di ards che richiede un'ecmo va. l'utilizzo della vena giugulare è descritto nell'articolo di skarsgard et al. [ ] . viene praticata per un uso pediatrico (i vasi femorali non hanno un diametro sufficiente nel neonato o nel bambino piccolo), o per l'utilizzo dell'ecmo vv. il suo utilizzo è aumentato a causa del crescente uso della cannula a doppio lume bicava. allo stesso modo, i vari dispositivi di dialisi respiratoria sono preferibilmente impiantati nella vena giugulare interna destra. il rischio è la sindrome della vena cava superiore con possibile impatto sulla perfusione cerebrale. l'accesso arterioso sottoclaveare presenta gli stessi vantaggi dell'accesso arterioso ascellare. si raccomanda inoltre l'interposizione di un innesto vascolare tra la cannula di infusione e l'arteria. tuttavia, l'accesso arterioso sottoclaveare sembra allontanarsi dalla necessità di abduzione dell'arto superiore implicato. biscotti e bacchetta hanno recentemente descritto l'associazione dell'approccio sottoclaveare destro a un accesso venoso giugulare interno destro. questa configurazione di ecmo va è stata battezzata il "modello sportivo". in effetti, è riservato ai pazienti in cui è prevista l'assistenza circolatoria ambulatoriale [ ] . il posizionamento percutaneo di una cannula a doppio lume bicava nella vena sottoclaveare sinistra, sotto controllo scopico ed ecografico, è stato descritto da shafii et al. questa tecnica, da riservare ai pazienti di piccole dimensioni, presenterebbe il vantaggio di aumentare la mobilità dei pazienti vigili e di diminuire i rischi di infezione nei pazienti trecheotomizzati [ ] . la combinazione di un'ecmo con altri sistemi di supporto periferico (palloncino ci contropulsione intra-aortica, impella recover lp ® ) è possibile [ ] . nella maggior parte dei casi, l'ecmo è impiantata in un secondo tempo davanti alla mancanza di altri sistemi. dapprima introdotte chirurgicamente [ ] , le cannule venose sono, ad oggi, in gran parte poste per via percutanea [ ] . l'uso di una cannula a doppio lume bicava per ecmo vv percutanea è entrata nella routine e ha contribuito alla diffusione dell'ecmo [ , ] . in caso di approccio chirurgico, consigliato per le cannule arteriose, l'emostasi deve essere approfondita ed effettuata, se possibile, dopo il ripristino di pressioni di perfusione soddisfacenti per limitare il rischio di ripresa del campo chirurgico per l'emostasi. le cannule possono essere poste con l'aiuto di dilatatori, secondo la tecnica di seldinger. la puntura deve essere facile e non iterativa in modo da non lacerare i vasi sottostanti. la cannulazione periferica attraverso l'arteria femorale con cannule di oltre f espone al rischio di ischemia dell'arto inferiore. questa complicanza, riportata con frequenze estremamente variabili (da a %), ha portato alla creazione di una perfusione distale sistematica utilizzando uno shunt a livello dell'arteria femorale superficiale da parte di molte équipe [ ] . • i circuiti pre-eparinizzati: l'utilizzo di circuiti pre-eparinizzati sembra essere lecito, anche se i risultati riportati non sono univochi. il loro impiego permette di ridurre la terapia anticoagulante, cosa che porta a una diminuzione dell'adesione leucocitaria, una riduzione dei microtrombi e una riduzione dei sanguinamenti [ ] . • iniezione di eparina: all'inizio dell'ecmo, la dose di eparina standard è di ui/kg ( ui/kg in assenza di circuito preeparinizzato). • tre situazioni possono portare a non iniettare eparina: • posizionamento sotto massaggio cardiaco esterno per via di disturbi di coagulazione post-rianimazione; • politrauma, soprattutto in presenza di un trauma al bacino con ematoma retroperitoneale o cranico associato; • anticoagulazione efficace preliminare [ ] . • la gestione del sanguinamento in un paziente sotto ecmo è illustrata nella figura . il controllo del corretto posizionamento della cannula venosa è imperativo ed è meglio realizzato tramite ecocardiografia o altrimenti tramite radiografia del torace. dovrebbe essere realizzato idealmente prima di fissare la cannula per evitare manipolazioni multiple. l'estremità della cannula venosa deve situarsi all'aggettamento della vena cava inferiore nell'atrio destro in modo che il drenaggio sia ottimale. se la cannula è troppo prossimale alla vena cava inferiore, vi è il rischio di suzione della vena tramite aspirazione, una volta che il volume di sangue si riduce. deve essere lontana dal setto interatriale e dalla vena cava superiore per prevenire il collasso di questi elementi che inducono un'anomalia di drenaggio e il ricircolo in caso di ecmo vv a duplice sito. in caso di utilizzo di una cannula a doppio lume bicava, sembra vantaggioso posizionare il dispositivo sotto controllo ecocardiografico. l'estremità distale della cannula deve situarsi tra l'anastomosi della vena cava inferiore e delle vene sovraepatiche. l'orifizio di infusione deve situarsi in prossimità della valvola tricuspide. l'utilizzo di un doppler associato all'ecografia può essere utile per verificare il corretto posizionamento degli orifizi di drenaggio e l'orifizio di infusione. il corretto posizionamento delle cannule può essere oggettivato clinicamente da: • l'assenza di ricircolo; • l'assenza di drenaggio anomalo in un paziente euvolemico; • l'efficacia dell'assistenza meccanica. • parametri gasometrici: la sorveglianza dei parametri gasometrici deve tenere conto del tipo di assistenza e della posizione delle cannule. in un'assistenza vv, il monitoraggio non mostra peculiarità poiché una gasometria prelevata in posizione radiale permette di valutare il livello di ematosi globale. tuttavia, in un supporto va, si deve tener conto del sito di impianto delle cannule. se sono posizionate al triangolo femorale, è preferibile una gasometria radiale destra per valutare il rapporto tra il sangue proveniente dal cuore e quello proveniente dal supporto. inoltre, l'ossimetria giugulare o cerebrale fornisce preziose informazioni sul livello di ossigenazione cerebrale. qualunque sia il tipo di assistenza, è essenziale la valutazione frequente dell'ossigenatore e delle performance. si consiglia di confrontare i valori di po e di pco pre-e post-membrana regolarmente e ogni volta che l'ematosi del paziente si degrada. il ricircolo può essere oggettivato sul gas del sangue, confrontando la saturazione venosa di o (svo ) del paziente con la svo del sangue della cannula di drenaggio. per la pulizia del dispositivo, bisogna assicurarsi che i prodotti utilizzati siano compatibili con le diverse componenti della ecmo. infatti, i prodotti alcolici utilizzati sui policarbonati creano delle lesioni a basso suono con rischio di porosità e lacerazioni. occorre effettuare una sorveglianza oraria stretta del circuito (fig. ). la ventilazione è fornita sia dalla ecmo (portata di gas, fdo , ossigenatore) sia dall'apparato respiratorio del paziente (funzionalità polmonare, ventilatore). nella configurazione va e femorofemorale, l'ossigenazione è assicurata in maniera schematica dal polmone nativo per la metà superiore (riflesso saturazione pulsata di ossigeno [spo ] a livello della testa o delle mani, gds radiale) e dall'ecmo per la metà inferiore (riflesso spo a livello dei piedi e gds nella femorale). il rischio principale è un'ipossiemia nella metà superiore del corpo per effetto shunt (a seconda dell'efficacia del polmone nativo) in caso di diminuzione dei parametri ventilatori. È pertanto indispensabile oggettivare la qualità di ossigenazione dei due settori e soprattutto di quello superiore. in caso di ipossiemia dell'emicorpo superiore su ards refrattaria alla terapia medica (fdo ottimale, positive end-expiratory pressure [peep] , no, almitrina, posizione prona): • se è richiesto un supporto emodinamico, è necessario modificare il circuito: • o inserendo la cannula arteriosa nell'ascellare destra [ ] , • o facendo risalire la cannula arteriosa in aorta toracica discendente, • o modificando il regime di assistenza per un'ecmo vva; • se il supporto emodinamico non è necessario, si deve: • o modificare il circuito passando alla modalità ecmo vv, sapendo che in termini di ossigenazione e di flusso, il circuito vv femorogiugulare interno destro è il più efficiente [ ] , • o procedere all'ablazione dell'ecmo e posizionare il paziente in decubito prono. È da notare la particolarità dell'ecmo vv in rapporto all'ecmo va. infatti, la gestione dell'ipossiemia severa in vv richiede un aumento del flusso sanguigno e autorizza una sao più bassa dall' all' % se la svo è corretta e la tolleranza generale è buona (livelli di lattati, disfunzione d'organo). È lecito adeguarsi agli obiettivi raccomandati in cardiochirurgia sotto cec (pao attorno a mmhg) per prevenire lo stress ossidativo derivato dalla produzione di radicali liberi e di anioni superossidi dall'effetto tossico. perciò, è comunemente accettato offrire: • il mantenimento della funzionalità del polmone; • una pao sopra - mmhg (o - kpa) con normocapnia, a livello dell'emicorpo superiore e inferiore. questo fenomeno è direttamente correlato alla non-occlusività della pompa centrifuga. corrisponde ad un arresto del flusso sanguigno, oppure a un'inversione del senso del flusso al di sotto di una certa portata rilasciata dalla pompa. questa è in funzione delle resistenze a valle e della qualità della contrattilità del ventricolo sinistro. questo fenomeno si osserva in primo luogo allo svezzamento dall'assistenza va e per una portata inferiore a , l/min. il fenomeno del back flow non si verifica in corso di assistenza vv, dal momento che le resistenze legate allo scambiatore impediscono la comparsa di un tale fenomeno. il verificarsi di trombi nel circuito rimane una complicanza comune, nonostante i circuiti pre-eparinizzati e il monitoraggio della terapia anticoagulante. la comparsa di trombi aumenta con la durata dell'ecmo. se la presenza di microtrombi è inevitabile, " condotta da tenere fenomeno del back flow • evitare di ridurre la portata della pompa sotto a , l/min. • monitorare attentamente la fase di svezzamento. • se si verifica un back flow: far salire la portata. -in caso di deficit del pre-carico: riempimento. -in caso di eccesso di post-carico: vasodilatatore (ecmo va). -allo svezzamento: aumentare la velocità della pompa. ma normalmente innocua, non è la stessa cosa per i trombi di grosse dimensioni. questi possono essere la causa di un guasto dell'ossigenatore o di complicanze emboliche. " condotta da tenere trombi • esaminare il circuito (in particolare l'ossigenatore) per almeno otto ore. • dopo la comparsa del primo trombo: discutere un cambiamento sistematico dell'ossigenatore o quando il rapporto pao /fio è inferiore a , o anche a (anche in assenza di trombi significativi). equivale a un vero e proprio edema polmonare acuto di membrana. i fattori favorenti principali sono: il tipo di ossigenatore utilizzato (quelli in polimetilpentene sarebbero tra i più resistenti) e l'importanza della sindrome infiammatoria [ ] . fuga plasmatica a livello dell'ossigenatore • monitorare l'ossigenatore. • cambiamento sistematico dell'ossigenatore quando il rapporto pao /fio è inferiore a , o addirittura a . l'usura della pompa è essenzialmente correlata alle sollecitazioni meccaniche che vengono applicate sulla parte rotante. la disfunzione si manifesta inizialmente tramite una modifica del rumore della pompa all'auscultazione. le pompe più comunemente utilizzate hanno una durata di vita di tre settimane. " condotta da tenere usura della pompa • da parte del team di accoglienza del paziente: auscultazione della pompa ogni otto ore, questo fin dall'inizio per poter valutare una modifica del rumore. • da parte del team responsabile dell'assistenza: visita bigiornaliera per fare il punto ed essere reperibile in caso di bisogno. • cambiamento della pompa sistematica: -o quando viene raggiunta la durata di vita teorica; -o dopo il verificarsi di un rumore che fa sospettare un'usura. esistono diverse fonti di embolia gassosa a partire dal circuito. la prima causa, di gran lunga la più frequente, è la manipolazione del circuito (durante i prelievi o durante l'utilizzo del circuito come via di riempimento la possibilità di effettuare lo svezzamento è in funzione dell'eziologia del processo che ha condotto all'impianto dell'ecmo. oltre le indicazioni dell'ecmo per assistenza temporanea durante la realizzazione di un procedimento terapeutico, bisogna, per le altre eziologie, attendere almeno ore. questo tempo minimo corrisponde al tempo di recupero degli organi, in particolare del polmone. i principi generali dello svezzamento sono: • graduale diminuzione del flusso dell'ecmo in - ore (o con gradienti di , l/min, cioè diminuendo il flusso del % in h) fino ad un flusso minimo compreso tra , e , l/min; monitoraggio sincrono della pao (indicazione respiratoria) e della pressione arteriosa media (indicazione cardiocircolatoria); • progressiva riduzione del flusso di gas fresco in funzione della paco ; • mantenimento di un indice cardiaco superiore a , l/min/m , senza significativa riaccensione del supporto inotropo; • mantenimento dell'ematosi dell'apparato respiratorio, senza ricorso a parametri ventilatori a rischio iatrogeno. la decisione di ablazione viene presa dopo qualche ora di osservazione. lo svezzamento da un'ecmo vv può essere lungo. corrisponde al tempo di riabilitazione polmonare. possono passare diverse settimane o diversi mesi. lo svezzamento da un'ecmo va dovrebbe essere più breve. l'impossibilità di svezzamento da un'ecmo va deve orientare verso un dispositivo di assistenza circolatoria di lunga durata o verso un trapianto cardiaco. lo svezzamento dalla ventilazione meccanica e il risveglio del paziente può/deve essere sincrono al fine di limitare i rischi connessi a una rianimazione prolungata e avere una partecipazione attiva nella cura e nelle decisioni. durante lo svezzamento, non dobbiamo dimenticare: • di aggiustare i parametri del ventilatore, sapendo che non è raro osservare un'ipossiemia transitoria durante lo svezzamento, che risponde all'aumento della fio , no e peep; • di aumentare l'act tra a secondi quando il flusso della pompa scende sotto l/min (tabella ). lo svezzamento dall'arec è possibile quando aumentano le compliance polmonari e lo stato clinico generale del paziente migliora. i parametri di ventilazione meccanica compatibili con lo svezzamento dall'ecmo sono: • in un paziente sedato: fio inferiore al %, peep inferiore a cmh o, pressioni di plateau inferiori a cmh o, volume corrente di ml/kg; • in un paziente sveglio: fio inferiore al %, peep inferiore a cmh o, con pressioni di sostegno inferiori o uguali a - cmh o, volume corrente maggiore o uguale a ml/kg. riguardo all'ecmo, esistono due strategie di svezzamento: • flusso di gas ridotto fino a - l/min, fdo gradualmente ridotto fino al %, flusso di sangue di , l/min; • o arresto degli scambi gassosi tramite arresto del fgf mantenendo un flusso di sangue extracorporeo a , l/min per prevenire la formazione di trombi nel circuito. una volta ottenuti questi parametri, se l'emostasi del paziente è mantenuta e i gas del sangue rimangono a livelli soddisfacenti, l'arec viene arrestata tramite rimozione della o delle cannula/e. la rimozione delle cannule di un'ecmo vv si effettua in rianimazione, al letto del paziente, e necessita un chirurgo toracico, un medico anestesista, un perfusionista e un infermiere. la rimozione della cannula venosa viene effettuata per semplice ritiro della stessa, sutura cutanea, e poi compressione manuale di dieci minuti. la rimozione delle cannule va, av o vva si effettua in sala operatoria. i vasi vengono sezionati e controllati a monte e a valle del punto di inserimento della cannula. la vena è richiusa con sutura continua. per quanto riguarda le arterie, è auspicabile un'embolectomia con sonda di fogarty del segmento a valle, come anche un'arterioplastica. • volume attuale = ml/kg; • fgf = l/min o fgf = l/min + fdo = %; • flusso della pompa = , - , l/min. sembrano imporsi due tecniche in caso di scompenso ipercapnico: la dialisi respiratoria e l'ecmo av. in assenza di instabilità emodinamica, i dispositivi di dialisi respiratoria hanno il miglior rapporto beneficio/rischio. la mancanza di prospettiva su questa tecnica può costringere ad usare un'ecmo av o un'ecmo vv. in caso di insufficienza emodinamica associata, è indicata un'ecmo va. in caso di insufficienza respiratoria isolata, l'ecmo è la tecnica di riferimento. la presenza di insufficienza emodinamica richiede l'uso di un'ecmo va o vva. in questo caso particolare, la tecnica da utilizzare è principalmente l'uso di un'ecmo ap-as senza pompa. questa tecnica permette il significativo miglioramento dell'ematosi così come un rimodellamento ventricolare destro. algoritmo decisionale (fig. ) la scelta della tecnica è mostrata in figura . la diminuzione del flusso di ventilazione e della pressione delle vie aeree durante l'assistenza respiratoria cec con depurazione di co riduce le sollecitazioni meccaniche imposte al polmone e al cuore, garantendo un ph normale, una paco normale e un miglioramento dell'ossigenazione. sono stati apportati considerevoli miglioramenti a questa tecnica dopo i primi studi realizzati nell'adulto negli anni . • accessi vv piuttosto che va; • incannulamento percutaneo anziché chirurgico; • pompa non occlusiva; • circuiti pre-eparinizzati; • ottimizzazione dei regimi del respiratore sotto ecmo; • gestione nei centri di riferimento. i progressi tecnici recenti e le politiche di sanità pubblica hanno contribuito a diffondere la tecnica, i cui risultati positivi rimangono stabiliti nei centri di riferimento: centri di chirurgia cardiaca, centri di trapianto polmonare, e di rianimazione specializzati nell'ards. allo stato attuale, le specifiche delle nuove metodiche assistenziali respiratorie devono attenersi alle esigenze seguenti: • agevolare l'attuazione per un utilizzo più frequente: gestione ambulatoriale con trasferimento secondario verso strutture adeguate; • progressività all'interno di un protocollo ben definito; • essere il più innocuo possibile (riduzione del numero e della dimensione degli accessi vascolari); • biocompatibilità e riduzione delle dosi di eparina. l'idea principe da ricordare è quella di sviluppare il concetto di strategia minimalista con l'uso di una cec adiuvante parziale -più che sostitutiva totale -che permetterebbe il recupero metabolico ed emodinamico ad integrum del paziente. nei prossimi anni, una migliore conoscenza delle indicazioni e il perfezionamento delle tecnologie dovrebbero migliorare la prognosi dei pazienti che beneficiano di un'assistenza meccanica. allo stesso modo la miniaturizzazione dei dispositivi e la bioingegneria dovrebbero aumentare la mobilità dei pazienti o aprire la strada all'arec di lunga durata. principi e indicazioni dell'assistenza circolatoria e respiratoria extracorporea in chirurgia toracica " punti importanti • l'ecmo è una tecnica di assistenza meccanica sostitutiva indicata: in caso di insufficienza respiratoria e/o cardiocircolatoria refrattaria a un trattamento medico ottimale; -in assenza e nella prevenzione dell'insufficienza d'organo(i) associata. • l'ecmo vv è superiore alla ecmo va per l'ossigenazione cerebrale, cardiaca e polmonare. • l'ossigenazione dipende principalmente dal flusso sanguigno della cec. • la decarbossilazione dipende dal flusso di gas fresco chiamato fgf ed è indipendente dal flusso sanguigno della cec. • la scelta della tecnica utilizzata è guidata dal contesto clinico e nosologico. • l'ecmo in combinazione con una ventilazione meccanica protettiva (volume corrente = - ml/kg; pressione di plateau < cmh o), sembra aumentare la sopravvivenza dei pazienti colpiti da ards severa refrattaria della classificazione di berlino. • nel trapianto di polmone: -la strategia di ecmo vigile in attesa di trapianto di polmone sembra superiore all'associazione ecmo + ventilazione meccanica, in termini di sopravvivenza, di comorbilità e di degenza ospedaliera; nei centri specializzati, i risultati dell'ecmo va come supporto intraoperatorio sembrano superiori a quelli della cec convenzionale, in termini di trasfusione, di durata media di ventilazione meccanica, di durata media di degenza in rianimazione e ospedaliera, e di sopravvivenza; -l'ecmo è associata ad una ventilazione protettiva per le dpi di grado iii refrattarie al trattamento medico ottimale; la prognosi sarà 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cord- -nnvco de authors: haye, guillaume; fourdrain, alex; abou-arab, osama; berna, pascal; mahjoub, yazine title: covid- outbreak in france: setup and activities of a mobile extra corporeal membrane oxygenation (ecmo) team during the first weeks date: - - journal: j cardiothorac vasc anesth doi: . /j.jvca. . . sha: doc_id: cord_uid: nnvco de nan the sars-cov- related disease is mainly characterized by respiratory manifestations with approximately to % of patients developing ards . the world health organization guidelines recommended to proceed to veno-venous extracorporeal membrane oxygenation (ecmo) for eligible patient with covid- related ards only in centres with "sufficient cases volume to ensure clinical expertise" . the amiens ecmo center received many calls during the first weeks from several hospitals of the region for refractory ards secondary to covid- . decision was rapidly made to set up a mobile ecmo team in order to start ecmo treatment on sites. located in the north of france, picardy region has a population of . million inhabitants on a km² territory. a network of general hospitals is located on this regional territory, with intensive care units (icu) beds. the only icu of picardy with the ability to manage ecmo is the cardiac thoracic vascular and respiratory unit of amiens university medical centre. the unit initiated about ecmo treatments every year (one third of venovenous ecmo) for more than years. the outbreak occurred in picardy at the end of february resulting in a rapid tension on icu beds. calls from peripheral centres for ecmo need increased rapidly. in one month (march ), patients were admitted in the hospitals of the region for covid- related disease. among them patients required icu admission ( admission rate: . %) . clustering infected patients requiring ecmo within an expert centre was necessary in order to insure adequate care and resource management. a unique phone number was publicized to all icus of the region in order to centralize request for ecmo. an on-call ecmo team member was able to give advice and to evaluate the need for ecmo. all ecmo team members were educated on the management and the eligibility criteria for ecmo initiation. the mobile ecmo team was composed by a specialized intensivist, a thoracic surgeon and a trained perfusion nurse. a roster was started in order to make the team available hours a day and days a week. decision to initiate ecmo treatment was always a multi-consultant decision. the ecmo team was able to reach any hospital of the region in less than minutes (by road or by air depending on the weather). the ecmo team decided on arrival to retrieve the patient on conventional ventilation or to initiate ecmo on site and transfer the patient on ecmo support. patients under ecmo were admitted in a specialized icu with trained staff. the cardiohelp® (maquet medical system, wayne, usa) ecmo device was used for each transport because of its compact and light design ( kg). during march , calls were received at our ecmo centre. the ecmo team initiated veno-venous ecmo treatments on site and transferred patients on conventional ventilation. for all patients, the drainage cannula (size of fr) was inserted in the right femoral vein and the return cannula (size of fr) was inserted in the right jugular vein. heparin treatment was started after the procedure with continuous perfusion of unfractioned heparin for an anti-xa level target of , - , ui.ml - . despite this treatment, canula thrombosis occurred for patients leading to procedure failure and death of the patients. this is probably due to the high inflammatory state that increases the risk of thrombosis as suggested in some reports clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in clinical management of severe acute respiratory infection when novel coronavirus ( -ncov) infection is suspected: interim guidance covid- respiratory failure: targeting inflammation on vv-ecmo support extracorporeal membrane oxygenation for coronavirus disease extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in covid- : experience with patients first successful treatment of covid- induced refractory cardiogenic plus vasoplegic shock by combination of pvad and ecmo -a case report the authors thanks all the nursing and perfusion staff for their commitment. the authors have no conflict of interest to declare only institutional funds were used. key: cord- - vdd mu authors: abrams, darryl; lorusso, roberto; vincent, jean-louis; brodie, daniel title: ecmo during the covid- pandemic: when is it unjustified? date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: vdd mu nan darryl abrams , , roberto lorusso , jean-louis vincent and daniel brodie , * the coronavirus disease (covid- ) pandemic has led to a critical shortage of resources in the hardest-hit areas around the world [ ] . intensive care units (icus) overwhelmed by critically ill patients may create non-conventional icu spaces and even consider triaging invasive mechanical ventilation to those most likely to benefit [ ] . in the most severe cases of refractory hypoxemia, extracorporeal membrane oxygenation (ecmo) may be considered, as recommended by the world health organization for severe covid- . early data suggest there may be a benefit from ecmo in certain patients with covid- -associated respiratory failure, though outcomes are likely to be highly dependent on patient selection and timing of ecmo initiation [ ] . whether certain phenotypes of covid- (if present) have differential responses to and prognoses with ecmo remains to be determined [ ] . an important question then is whether a resource-intensive therapy is warranted when systems are already strained [ ] . the high severity of the respiratory failure in some patients with covid- anticipates the need for ecmo in a large number of patients. however, circumstances that limit otherwise readily available resources raise the threshold for initiating more complex therapies. therefore, in the context of the covid- pandemic, adherence to evidence-based algorithms is necessary to optimize the allocation of limited resources. every effort should be made to apply established, less invasive strategies, including prone positioning and optimization of volume status, prior to consideration of ecmo in these patients [ ] , but ecmo may still be required. in fact, the limited availability of ecmo, due in part to shortages in ecmo equipment and insufficient capacity at ecmocapable centers, may lead to the unanticipated benefit of more widespread adoption of these proven therapies that often go underutilized [ ] . perhaps the initial question should not be when, but whether to use ecmo at all in the covid- pandemic. analyses have demonstrated a benefit from ecmo in severe forms of the acute respiratory distress syndrome (ards) [ ] , though such benefit comes at real costs, and not simply financial ones. in the case of a pandemic requiring crisis standards of care, every resource has the potential to become critical to the functioning of an icu or the care of critically ill patients. most prominently, staffing may emerge as a critical bottleneck. the use of ecmo taxes many resources, but none more so than staffing-increased nursing ratios, need for ecmo specialists, disproportionate medical provider time, not to mention other staff, such as respiratory or physical therapists, who would be needed elsewhere for the care of other patients [ ] . given that staffing may already be maximally strained, the excess resources needed for the ecmo patient will negatively and disproportionately impact the care of non-ecmo patients relative to the addition of another critically ill patient not receiving ecmo. during a crisis, ecmo may not be a zero-sum game. the inability to manage this strain will likely be greatest among lower-volume, less-experienced ecmo centers, providing rationale for the regionalization of ecmo [ ] , an approach which itself may be further limited by excess patient volume at all centers, resulting in suboptimal provision of care to ecmo patients in general. in this context, can ecmo be justified in the epicenter of a pandemic? during non-pandemic times, in hospitals or regions with sufficient staffing reserves and provider availability, it may be understandable why clinicians might attempt ecmo in a candidate with a low, but acceptable, probability of benefit (e.g., a post-partum patient with refractory shock in multisystem organ failure). yet, one would be hard-pressed to justify the same approach if it meant a tangible sacrifice in the care of other patients in whom there is greater likelihood of favorable outcomes. effectively, at times of substantially increased strain on hospital and healthcare systems, there needs to be more judicious patient selection, reserving ecmo only for those patients who are most likely to derive benefit, assuming an acceptable level of care can be maintained for other patients, in an attempt to achieve the greatest benefit for the greatest number of patients-a utilitarian standard that may apply under crisis standards of care. beyond withholding ecmo, the most dire of situations may seem to necessitate the withdrawal of ecmo from those in whom there is no perceived chance of meaningful recovery-regardless of the opinion of the patient or surrogate decisionmaker [ , ] . triage committees may be helpful to help determine the allocation of resources under such circumstances [ ] . the use of ecmo in a pandemic can be seen following a u-shaped curve (fig. ) , rising as the number of cases rises, decreasing as resources become increasingly scarce, and possibly rising again as strain eases on the back-end of the crisis or trailing off as the number of patients qualifying for ecmo likewise tapers down. of course, under the most extreme of circumstances (at the bottom of the curve), ecmo may have to be abandoned altogether [ ] . therein lies the key principle: the use of ecmo should not be considered in a vacuum; the consequences of choosing to initiate ecmo in a crisis are not just borne by that patient alone. fig. potential curve of ecmo case volume during the covid- pandemic. during surge conditions, ecmo usage will be variable (red dashed line), including the potential of being abandoned altogether. as the pandemic resolves and patient volume decreases, there may be increasing resource availability and ecmo use (blue arrow) or decreasing demand (green arrow) epidemiology, clinical course, and outcomes of critically ill adults with covid- in new york city: a prospective cohort study considerations for ventilator triage during the covid- pandemic the role of ecmo in covid- : can it provide rescue therapy in those who are critically ill? covid- -associated acute respiratory distress syndrome: is a different approach to management warranted? who clinical management of severe acute respiratory infection (sari) when covid- disease is suspected: interim guidance ecmo for ards: from salvage to standard of care? unproven and expensive before proven and cheap: extracorporeal membrane oxygenation versus prone position in acute respiratory distress syndrome venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients ethical aspects of the covid- crisis: how to deal with an overwhelming shortage of acute beds ethical dilemmas encountered with the use of extracorporeal membrane oxygenation in adults the toughest triage -allocating ventilators in a pandemic understanding pathways to death in patients with covid- publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations authors' contributions da and db wrote the first draft of the manuscript. rl and jvl reviewed and edited the manuscript. all authors read and approved the final manuscript. key: cord- -khgneone authors: bleakley, caroline; smith, miss rosie; garfield, benjamin; jackson, timothy; remmington, chris; patel, brijesh v.; price, susanna title: contrast echocardiography in vv-ecmo dependent covid- patients date: - - journal: j am soc echocardiogr doi: . /j.echo. . . sha: doc_id: cord_uid: khgneone nan the use of contrast echocardiography in patients receiving veno-venous ecmo (vv-ecmo) for severe acute respiratory failure (sarf) is not widely published, and there is understandable caution surrounding its use in this population. the novel coronavirus (covid- ) pandemic resulted in an unprecedented burden on critical care facilities ( ) due to sarf. our centre is one of nationally commissioned vv-ecmo services in the united kingdom and has seen vv-ecmo activity quadruple during the first pandemic surge. consequently, there has been growing emphasis on transthoracic echocardiography (tte) to diagnose cardiac complications of covid- supported with vv-ecmo ( , mechanically ventilated patients receiving vv-ecmo are amongst the most challenging in which to obtain diagnostic tte images. predictably, we found that as the volume of vv-ecmo patients increased, so too did the requirement for tte using ultrasound enhancing agents (uea). contrast echocardiography is routinely used in our institution and this work was approved through the local governance board as a service evaluation. we carried out bedside tte in consecutive vv-ecmo patients, of which sonovue (bracco international) tte was performed in ( %). sonovue boluses ( . - . ml), reconstituted in the standard format, were administered via the post-oxygenator limb of the ecmo circuit. repeated boluses of the uea were required in all cases, with a maximum total dose in any one patient of . mls. all patients met criteria for the use of uea's as outlined in the recently published guidance ( ). very-low mechanical index imaging (vlmi) was performed with standard commercially available tissue cancellation sequences (philips healthcare, andover, ma). vlmi allows excellent tissue delineation and results in less microbubble destruction than the higher mechanical index left ventricular opacification (lvo) settings. diagnostic images were obtained in all cases. in line with our institutional protocols for critical care echo in extracorporeal support (developed in collaboration with our specialist perfusion team), during each contrast study the vv-ecmo circuit was managed by experienced perfusionists. this included disabling the appropriate interventions on the ecmo console prior to uea administration to ensure safe administration. uea's are known to activate the protective integrated air bubble alarms which trigger interventions to disable flow -a safety feature of the cardiohelp ecls system (maquet medical systems usa, wayne, nj) ( ) and in all cases, the integrated detector for air bubbles was indeed triggered by the uea. this would usually lead to a pump shut down due to activation of additional safety interventions and, unless this alarm is cleared, a further "zero-flow mode" is engaged. this mode provides sufficient revolutions per minute to prevent back flow from the return cannula without providing forward flow, hence equilibrium is maintained in the circuit. however, the resultant cessation of flow, and consequently oxygenation, can result in rapid desaturation and potentially hypoxic arrest. it is therefore of pressing importance that centers offering vv-ecmo adopt protocols and staff training to allow the safe administration of uea's, facilitating diagnostic echocardiography in the most critical patients. to our knowledge, this is the largest published series affirming the applicability of a uea in vv-ecmo. appropriate protocols should be instituted at centers offering vv-ecmo, ensuring safe management of the circuit by the perfusion team. enhanced echocardiography may therefore be an appropriate bedside technique during the current viral surge in critical vv-ecmo supported sarf, helping to address diagnostic uncertainty in cases with challenging echocardiography visualisation. esc guidance for the diagnosis and management of cv disease during the covid- pandemic ase statement on protection of patients and echocardiography service providers during the novel coronavirus outbreak american society of echocardiography guidelines update beware of life-threatening activation of air bubble detector during contrast echocardiography in patients on venoarterial extracorporeal membrane oxygenator support key: cord- - ioy r authors: usman, aa; han, j; acker, a; olia, s; bermudez, c; cucchiara, b; mikkelsen, me; wald, j; mackay, e; szeto, w; vernick, wj; gutsche, jt title: a case series of devastating intracranial hemorrhage during venovenous extracorporeal membrane oxygenation for covid- date: - - journal: j cardiothorac vasc anesth doi: . /j.jvca. . . sha: doc_id: cord_uid: ioy r objective anticoagulation may be a challenge in coronavirus disease (covid- ) extracorporeal membrane oxygenation due to endothelial injury and dysregulation of coagulation, which may increase the risk of thrombotic and bleeding complications. this report was created to describe the authors' single institutional experience, with emphasis on the high rate of intracranial hemorrhage for the first patients with covid- placed on venovenous extracorporeal membrane oxygenation (vv ecmo). design case series, retrospective analysis. setting single institution. participants ten patients. interventions none. measurements and main results patient characteristics, mortality, stroke rate, and length of stay data were collected in all patients. in addition, laboratory values of d-dimer and c-reactive protein and standard measurements of prothrombin and activated partial thromboplastin time were collected on all patients. ten patients, each confirmed with covid- via reverse transcription-polymerase chain reaction, were supported on vv ecmo for acute respiratory distress syndrome (ards) for a mean duration of . ± days. four of patients had hemorrhagic strokes, of which resulted in death. at days after initiation of vv ecmo, a total of survivors included patients discharged from the hospital and patient who remained in the intensive care unit. conclusions in this small study of patients, intracranial hemorrhage was a common complication, resulting in a high rate of death. the authors urge caution in the anticoagulation management of vv ecmo for patients with severe ards and covid- patients. close monitoring of all hematologic parameters is recommended during ecmo support while awaiting larger, multicenter studies to examine the best practice. infection with severe acute respiratory coronavirus (sars-cov ) was designated a worldwide pandemic in march of . corona virus disease , the illness caused by sars-cov , has rallied the world behind efforts to investigate and report the optimal clinical management and treatment for this disease. despite maximal medical therapy, covid- can progress to severe, refractory acute respiratory distress syndrome (ards) prompting clinicians to consider utilization of extracorporeal membrane oxygenation (ecmo) in appropriate cases, although early reports appeared to have high rates of mortality. in general, patients with severe ards supported with vv ecmo are anticoagulated to reduce the risk of circuit clot or associated venous thromboembolism. patients with covid- demonstrate complex pathophysiology with multi-organ involvement; in particular, changes in patients' coagulation profiles stemming from the combination of inflammation and vascular endothelium activation. , in addition, arterial and venous thrombosis appears to a potential source of the organ dysfunction seen in covid- patients. , the risks and benefits of anticoagulation and the complex interplay between covid- infection, inflammation, and hypercoagulability in this population remains unstudied in the setting of vv ecmo. this case series describes our single institutional neurological outcomes for the first ten patients placed on vv ecmo for covid- , of whom three had severe intraparenchymal hemorrhagic strokes resulting in death, one patient had a small subarachnoid hemorrhage and one patient had severe gastrointestinal bleeding. this case series describes a hemorrhagic stroke rate that far exceeds that expected for vv ecmo treatment in severe ards. this study was approved by the institutional review board at the university of pennsylvania. our ecmo team consists of a multi-disciplinary group that have managed a robust vv-ecmo lung rescue program including the ability to perform mobile ecmo. , a decision was made to continue utilizing vv-ecmo during the covid- pandemic with rigorous, multidisciplinary patient selection. due to limited access to ecmo circuits and concern about an overwhelming number of consults for ecmo, we restricted our previously published criteria to the following: all patients in this study were cannulated at our institution or at an outside hospital by our mobile ecmo team, and were subsequently admitted to specialized units staffed by critical care specialists and highly skilled icu nurses trained in ecmo management. ecmo circuits were standardized per our institutional practice. cardiohelp and rotaflow (maquet getinge group, germany) devices were used for all patients, with standard cannulation using a femoral venous inflow cannula and a right internal jugular outflow cannula. patients' pump settings and lab values were obtained at close intervals for pre-and post-oxygenator monitoring. standard safety check lists included safety hand crank, wall, as well as tank oxygen supply were permanently placed at the bedside. our standardized protocol for anticoagulation of patients on vv-ecmo utilizes a heparin infusion targeting an aptt of - seconds and - seconds if oxygenator failure or evidence of clotting occur. reference range for normal aptt at our institution is . - . seconds. one patient was anticoagulated with a bivalirudin infusion due to problems with recurrent clotting of their continuous renal replacement therapy circuit while on a heparin infusion prior to ecmo support. all patients at the time of cannulation received a standard unit/kilogram intravenous unfractionated heparin bolus. heparin infusion was started after cannulation and adjusted per our institutional provider-driven protocol, with aptt measured every six hours initially and every twelve hours once target range was achieved. additional standard lab values were collected at daily intervals including d-dimer, ferritin, fibrinogen, ptt, pt, inr, and platelet counts. between / / to / / , patients meeting inclusion criteria with severe refractory ards due to covid- who failed a trial of proning therapy with a muscle relaxant infusion were placed on vv ecmo. patients were considered if their pao /fio was < on % oxygen with appropriate positive end expiratory pressure. , retrospective chart review was performed on all patients with covid- requiring vv ecmo. all data was reviewed by two independent reviewers aau and jh. data was placed in excel (microsoft). data was summarized with means, standard deviations, and proportions within each cohort. each cohort was analyzed and compared using a χ test or fisher's exact test for categorical variables and kruskal-wallis tests for continuous variables. all analyses were performed using stata (statacorp, college station, tx), and a p< . was defined as statistically significant. data for patient specific averages are reported as mean +/- th / th quartile ranges. data for laboratory data is reported as mean +/-standard deviation. the primary outcome was incidence of any type of stroke for the duration of vv ecmo. a diagnosis of stroke was suspected based on bedside findings of focal neurologic deficits, notably an abnormal pupillary exam in cases treated with heavy sedation and neuromuscular blockade agents. a stroke alert with a formal emergency neurology consultation and a ct scan was obtained in all cases of suspected stroke. intracranial bleeding was categorized as subarachnoid hemorrhage (sah), intraparenchymal hemorrhage (iph), or intraventricular extension of iph. ischemic stroke was defined by large vessel occlusion and evidence of ischemia or infarction on ct scan. secondary outcomes evaluated include total days of ecmo support, time to decannulation, time to tracheostomy and -day survival. we also evaluated patients for -day neurological status post admission, number of circuit exchanges required for oxygenator clot, cvvh circuit exchange events due to clot, and evidence of pulmonary embolism. lab values were also recorded and analyzed daily and at the time of stroke evaluation. ten patients, each confirmed covid- cases via rt-pcr, were cannulated for vv ecmo for were temporally related to the -hour period preceding the stroke diagnosis. the fibrinogen level on average was higher in the stroke patients versus the non-stroke patients . +/- . versus . +/- . (p < . ). there was a total of circuit exchanges during the total of ecmo days in the patients. out of circuit exchanges occurred in the patients with stroke. all circuit exchanges occurred due to rapidly declining oxygenator function due to clot with a pao /fio < on % oxygen. one circuit exchange occurred in the non-stroke group due to oxygenator clot and the last circuit exchange occurred in order to make a mobile transport console available for clinical use. all patients without stroke were neurologically intact and participating in physical therapy at the time of discharge. to our knowledge, this report is the first of its kind to focus on the rate of intracranial hemorrhage for covid- patients on vv ecmo. covid- is a new disease and it is important to report early institutional experiences which may impact patient management at other ecmo hospitals. to better understand how unusual this rate of ich is in vv ecmo, we reviewed the literature. nasr et al., analyzed data from the nationwide inpatient sample from - , including , adults who received vv or va ecmo. the authors found that . % suffered neurologic complications but only . % had ich. this sample, although large, included va and vv ecmo which have different anticoagulation requirements and risk profiles. in addition, this study did not report if the ich occurred while patients were on ecmo or after decannulation, but only noted that ich occurred prior to hospital discharge. lorusso and colleagues, analyzed data from the extracorporeal life support organization to assess the incidence of neurologic outcomes in patients supported with vv-ecmo. in an analysis of , patients supported with vv ecmo for non-covid- related respiratory failure, ich was diagnosed in ( . %) patients with a mortality of . %. the cesar trial found neurologic injury was observed in % of patients, however the type of neurologic injury was not differentiated into subtypes. in the eolia trial, of the patients randomized to ecmo support, patients suffered from hemorrhagic stroke. our center has extensive experience offering ecmo to patients with severe ards including a mobile program which has been able to continue implementing ecmo cannulation in regional hospitals in a limited fashion during this pandemic. to date, at our institution, we have had less than % intraparenchymal hemorrhage during non-covid lung rescue vv ecmo in patients since . this unprecedented intracranial hemorrhage rate in covid related ards requiring vv ecmo has prompted an evaluation of our anticoagulation practice by experts in hematology and neurology. in an abundance of caution, we are now using vte prophylaxis dose - units of subcutaneous heparin three times a day and mg of aspirin daily for covid- patients on vv ecmo. using vte prophylaxis alone has been utilized by others. krueger et al. in described their experience with sixty-one patients with subcutaneous enoxaparin alone. the authors found thrombotic complications in four patients, three of them in the centrifugal pump after a runtime of more than days. no intracranial hemorrhages were reported in this single center retrospective analysis. we opted for this approach after extensive discussion with hematology and neurology experts keeping in mind the fatal nature of the iph we experienced. although we temporarily ceased using heparin infusions in covid- ecmo patients, we have not yet experienced an increase in fatal thrombotic complications or reduced circuit durability. the three initial reports from wuhan, china reported the use of ecmo in / , / , and / critically ill covid- patients. , , the neurological outcomes for ecmo patients in these studies were not reported. recently, jacobs et al. describes the outcomes of ecmo patients in hospitals. fifteen patients were decannulated and ten of these patients had died. one patient death was attributed to intracranial hemorrhage and two to dic. the extracorporeal life support organization has created a live covid ecmo dashboard and to date, may , , the report records completed ecls runs with a total of stroke (< %) and intracranial hemorrhage ( %). the granular neurological and hematological outcomes data for covid- from the currently published literature is limited and it remains unclear if centers are experiencing similar rates of intracranial hemorrhage or bleeding complications such as dic. evidence is mounting that a subset of covid- icu patients can progress to a disseminated intravascular coagulopathy (dic). , elevated d-dimer and fibrin/fibrinogen-degradation products have been identified as an early marker for disturbances in the coagulation pathway, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. it is also possible that aptt may inadequately measure anticoagulation levels in patients with covid- , but it is unclear why this would only manifest as increased bleeding in vv-ecmo patients. for future patients, we will consider using heparin assay results in conjunction with aptt to guide anticoagulation. prior to , our institution regularly used activated clotting time to guide anticoagulation with heparin infusion. anecdotally, our patients suffered from much higher rates of bleeding complications in that era. vv-ecmo bleeding is typically associated with platelet dysfunction. , based on our results, patients who suffered from stroke had more ecmo circuit exchanges. this may simply be a marker for a prothrombotic state or risk for microvascular thrombosis that resulted in parenchymal cerebral hemorrhage. covid- appears to be an independent risk factor for coagulopathy and thrombosis, however the mechanism and pathophysiology is currently under active investigation. there have been reports of high rate of thrombotic complications including vte and stroke. however, the neurological and hematological outcomes of covid- are still emerging, even with pathology report data appear to indicate that thrombosis is the more common problem. it is essential to tease out the degree of contribution to coagulopathy from covid- in multiorgan system illness. ards, paralysis, and critical illness itself has been demonstrated to be a risk factor for thrombosis. it is unclear why the rate of ich in our covid- population was so high, but it may be related to vascular inflammation associated with covid- . there is continued evidence that covid- results in a cytokine storm and inflammatory cascade that may be exacerbated by extracorporeal circuitry and may be attenuated by anti-inflammatory agents (i.e., corticosteroids). in addition, biomarkers associated with thrombosis, such as d-dimer, and actual thrombotic event rates have been consistently elevated in covid- . , further study, designed to test the balance of required anticoagulation in covid- patients on ecmo are warranted. there are several limitations to the study which include the low number of patients studied. this report hopes to emphasize early reporting of sentinel unexpected events; however, results may be difficult to interpret due to low numbers. additionally, this represents a single institutional outcome. ecmo selection criteria vary from center to center, in addition ecmo capabilities fluctuate based on the level of the covid- surge capacity of a hospital system. furthermore, anticoagulation policies may vary across institutions. finally, conventional coagulation studies such as aptt testing may have limited predictive value for actual coagulation status in covid- and perhaps institutions should consider routine viscoelastic testing for this special patient population. our report demonstrates the other hematologic spectrum of covid- , in particular in the setting of anticoagulation and extracorporeal devices. this report highlights that this disease we now are grappling with is not just a prothrombotic disease; rather, a disease that causes severe imbalance in bleeding and thrombosis risk; in particular with extracorporeal circulation. based on our results we urge close evaluation of anti-coagulation strategies during the use of vv ecmo in covid- . furthermore, we suggest all ecmo programs internally evaluate their anticoagulation protocols. close neurological monitoring is recommended based on this limited case series. rapid reporting of complications remains essential as clinicians around the world apply various potentially lethal treatment modalities to this pandemic illness. sa: ecmo for ards due to covid- epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in covid- and its implications for thrombosis and anticoagulation covid- and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: jacc state-of-the-art review acute respiratory failure managed via inter-facility transport for extracorporeal life support: a -year experience does a mobile ecls program reduce mortality for patients transported for ecls therapy for severe acute respiratory failure? one-year experience with a mobile extracorporeal life support service ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome prone positioning in severe acute respiratory distress syndrome neurologic complications of extracorporeal membrane oxygenation neurologic injury in adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure: findings from the extracorporeal life support organization database efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for severe acute respiratory distress syndrome venovenous extracorporeal membrane oxygenation with prophylactic subcutaneous anticoagulation only: an observational study in more than patients clinical characteristics of coronavirus disease in china clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in coronavirus disease : experience with patients extracorporeal life support organization -registry dashboard covid- pulmonary arterial thrombosis in covid- with fatal outcome: results from a prospective, single-center autopsy findings and venous thromboembolism in patients with covid- acquired von willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: rapid onset and fast recovery megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in covid- : a case series covid- -related severe hypercoagulability in baseline data all patients (n= ) non-stroke (n= ) the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -cuau dcy authors: alom, samiha; haiduc, ana alina; melamed, naomi; axiaq, ariana; harky, amer title: use of ecmo in covid- patients: does the evidence suffice? date: - - journal: j cardiothorac vasc anesth doi: . /j.jvca. . . sha: doc_id: cord_uid: cuau dcy nan coronavirus disease (covid- ) caused by severe acute respiratory syndrome coronavirus (sars-cov- ) has gathered worldwide attention for its potentially fatal course and complex clinical manifestations. this novel virus primarily affects the cardiorespiratory system, which can lead to acute respiratory distress syndrome (ards) and shock [ ] . whilst severe and critically ill patients account for - % of patients, there are currently no targeted covid- therapeutics [ ] . at present, the mainstay of management is supportive care, with focus on delivering oxygen early in the disease course [ ] . in march , the world health organisation (who) released interim guidelines that advocate the use of extracorporeal membrane oxygenation (ecmo) to support the cardiorespiratory system in patients who fail maximal conventional therapies with ards [ ] . in this letter, we have performed a systematic review of literature to summarize the evidence behind using ecmo in covid- patients. we have performed a comprehensive electronic literature search following 'preferred reporting items for systematic reviews and metaanalysis' (prisma) guidelines and using key words 'covid- ' 'sars-cov ' 'coronavirus' 'ecmo' 'extracorporeal membrane oxygenation' 'va-ecmo' 'vv-ecmo' 'outcomes' 'respiratory support' 'circulatory support' either as mesh terms or in the combined key-word formats. our results showed a total of articles that were retrieved from the database search and through snowballing. following exclusion of duplicates and screening, a total of articles were selected for inclusion in this systematic review ( figure ). the characteristics of these studies are summarised in table . upon combining the data from all the studies, overall there were patients diagnosed with covid- , patients diagnosed with ards and placed on ecmo, with vv-ecmo being the most commonly utilised type. ecmo was often adopted as salvage therapy for patients commonly experiencing covid- -induced ards and/or other covid- complications [ ] [ ] [ ] [ ] . the overall mortality rate following the collation of the data from the articles selected in this review was . %. this value can, however, only be used as an estimate since some articles did not report mortality outcomes for their patients put on ecmo, making the mortality rate subject to increase. despite this, this figure shows promise that ecmo is not detrimental for critically ill patients with covid- . a small number of studies presented high rates of mortality for patients with covid- . three studies in this review reported % mortality for patients with ards put on ecmo, while yang et al reported a similarly high mortality rate of . % ( deaths in total) [ ] [ ] [ ] [ ] . in addition, guan et al reported that all patients that were put on ecmo experienced the composite primary endpoint that consisted of admission to the icu, use of mechanical ventilation or death [ ] . other studies reporting poor outcomes for ecmo include zeng et al [ ] . whilst patients did recover following ecmo, patients ( of which were comatose) remained on ecmo and patients died. despite this however, the study attributed half the deaths to septic shock and multiple organ failure which required va-ecmo support. while we are not sure whether the patients in question experienced multiple organ failure whilst on ecmo, if this was the case it would provide an explanation for the negative outcome due to the absolute contraindication between ecmo and multiple organ failure (as depicted in elso guidelines) [ ] . li et al depicted rather ambivalent results, reporting a % mortality rate [ ] . however, upon closer look at the demographic data, out of the deaths occurred in patients with comorbidities over the age of . similarly, marullo et al did not indicate any strong conclusions for the use of ecmo, whereby the difference between the number of patients weaned off ecmo ( ) and the number of deaths following ecmo ( ) was marginal [ ] . however, like li et al, the study highlighted the increased risk of patients over who possessed comorbidities, characteristics that were consistent with the mortality that was reported in the study. loforte et al also reported that out of patients were weaned off ecmo, and while a % weaning rate appears successful, one of the three weaned patients eventually died after vv-ecmo removal [ ] . the final patient died due to severe gastrointestinal bleeding while on ecmo, highlighting the potentially fatal complications associated with ecmo (with bleeding being the most frequent) [ ] . thus, with patients out of the four eventually expiring, this study also provides no conclusive indication of the effectiveness of ecmo for covid- whilst these studies have reported either negative or equivocal results, several considerations should be noted. firstly, many of these articles consist of a small sample and thus no reliable conclusions can be made. secondly, some of the articles did not provide information with regards to the patient's disease severity at the time of ecmo initiation, so we cannot know if ecmo was perhaps administered too late to have a significant effect in a severely deteriorating patient. many of the case reports/series included in this review reported positive outcomes, and while these studies cannot provide us with robust evidence to make overarching conclusions, they can help us identify patient characteristics that are ideal for ecmo. six case reports and two case series reported positive endpoints (weaned off ecmo/discharged from hospital) for patients on ecmo [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the literature posited that early timing of ecmo support may have resulted in successful outcomes. zhan et al and taniguchi et al indicated that early ecmo provision could have enabled the recovery of their patients, whereby their organ oxygen supply was protected and lung injury resulting from mechanical damage (ventilators) was avoided [ , ] . firstenberg et al, also highlighted that the most critical aspect to starting therapy is the timing between reaching the threshold for indication and the decision to begin therapy, whereby their judicious decision to initiate ecmo resulted in the patient's discharge [ ] . additionally, taniguchi et al highlighted how the use of ecmo to stabilise oxygenation and rest the lungs can also have a role in improving outcomes [ ] . recognition and treatment of the cause of deteriorating oxygenation is imperative. in the context of this case, the patient may have experienced worsening oxygenation due to aggravation of ards by covid- pneumonia. whereby inflammatory results were stronger than pulmonary congestion, ecmo was initiated to aid the patient's recovery [ ] [ ] [ ] . the main contraindications for the use of ecmo are summarized in table according to elsom guidelines. upon comparing our results to wider literature, we found that they have similarly endorsed the use of vv-ecmo. according to a systematic review and meta-analysis which included the cesar [ ] and eolia [ ] trials amongst others, the use of vv-ecmo in acute severe respiratory failure was associated with a -day reduced mortality (rr . , % ci . - . ) when compared with conventional mechanical ventilation [ ] . although the cesar study has been largely opposed by many clinicians, yet the eolia study showed no significant difference in overall mortality. additionally, elso also reported a % expected survival to discharge on va [ ] compared to % on vv [ ] , however this has not been compared to conventional care so the survival advantage of vv is unknown [ , ] . the use of vv-ecmo in covid- ards is supported by multiple guidelines [ , , , ] . vv-ecmo provides respiratory support and is most commonly used in severe respiratory failure. as sars-cov- pneumonia is characterised in most cases by acute respiratory failure with some progressing to ards, vv-ecmo has been increasingly used. in contrast, va-ecmo provides both respiratory and haemodynamic support and is used in cases of cardiogenic shock as a result of cardiac injury, myocarditis, acute myocardial infarction or decompensated cardiac failure. as covid- is associated with high incidence ( %) of cardiovascular complications, in particular myocarditis, heart failure and a prothrombotic state, va-ecmo could have an important role in these patients [ ] . drawing from data published so far, we propose the following algorithm outlined in figure . patients presumed suitable for ecmo should be identified early, to minimise the risk of complications associated with prolonged ventilator use. in addition, we suggest that if the decision to use ecmo is endorsed, referral to tertiary centres with established expertise and standardized ecmo protocols should ideally be done. additionally, since the combination of systemic inflammatory response and the need for anticoagulation in ecmo can lead to an imbalance in the pro and anticoagulant pathways and increase the risk of both thrombotic and haemorrhagic complications, care should be taken to ensure a balanced coagulation profile during ecmo [ ] . in addition to existing guidelines, several prediction tool scores including the preserve ( (auc . ( % ci . to . , p = . ) and resp scores (auc . ( % ci . to . , p = . ) have been developed to aid decision making regarding the use of vv-ecmo based on best predicted outcomes [ ] . the survival after veno-arterial-ecmo (save) score can be used to identify patients that would benefit more from va-ecmo and balance use with availability of resources [ ] . however, whilst these tools have been shown to be a good predictor of survival of patients with ards placed on vv-ecmo, they do not account for the unique pathophysiology involving the cytokine storm encountered in covid- patients. to conclude, there is currently not enough evidence to support ecmo utilisation in covid- , we recommend that ecmo should be used with caution and should comply with current guidelines. ongoing research should help in understanding this pattern and the benefit of ecmo in covid- patients on intensive care unit. a risk-benefit analysis should be undertaken for patients, and all decisions should be made on a case-by-case basis. due to the paucity of data in this area, particularly for use of va-ecmo, no reliable overarching conclusions can be made on ecmo utilisation for covid- . however, this perhaps be explained by the fact that ards (for which vv-ecmo is used) is far more prevalent among covid- patients compared to those with shock (where va-ecmo is used). secondly, since several studies did not report patient outcomes, we have gaps in our data as we cannot make any assumptions on whether ecmo has a positive or negative effect on the patients. the lack of data on outcomes also prevented us from performing a meta-analysis as the effect size could not be calculated. therefore, the overall mortality rate that we reported (which included studies without reported outcomes) may be subject to change. thirdly, as the characteristics of patients included in the studies were not always mentioned, we cannot make any assumptions on how ecmo reduces mortality in particular groups of people. since demographic factors and presence of comorbidities have great influence over covid- prognosis, these variables should be taken into consideration as potential determinants of patients' outcomes, alongside with initiation of ecmo as a treatment. while ecmo is usually provided alongside with a primary treatment, many of the patients received numerous alternative therapies on top of that. therefore, it is unclear to what extent ecmo utilisation contributed to treating and healing the patient. fourthly, there is inconsistency amongst papers regarding the threshold used for deciding the use of ecmo. for example, some patients may have received ecmo at later and more critical stages which would have had increased baseline risk of mortality. in addition, institutions with low numbers of ecmo machines may have prioritised critical patients, as they are in more need of salvage therapy which could have also reflected in the reported mortality rates (selection bias). additionally, use of different guidelines, if guidelines were used at all, may have also contributed to different outcomes in patients. therefore, although we have provided an overall mortality rate after collation of all the data, the rate estimate does not account for treatment variations (time of ecmo initiation and technique). pao :fio = ratio of partial pressure of oxygen in arterial blood to the fractional concentration of oxygen in inspired air. paco = partial pressure of carbon dioxide in arterial blood. emco = extracorporeal membrane oxygenation. peep = positive end-expiratory pressure. *l-phenotype has been associated with preserved lung compliance and shown to have favourable outcomes with ecmo [ ] . adapted from the extracorporeal life support organisation (elso) [ ] . [ ] . a review of coronavirus disease- (covid- ) clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china evaluation and treatment coronavirus (covid- ), in statpearls clinical management of severe acute respiratory infection (sari) when covid- disease is suspected: interim guidance sars-cov- in spanish intensive care units: early experience with -day survival in vitoria clinical features of patients infected with novel coronavirus in wuhan, china comparison of hospitalized patients with ards caused by covid- and h n characteristics, treatment, outcomes and cause of death of invasively ventilated patients with covid- ards in clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study clinical characteristics of coronavirus disease in china extracorporeal life support organization covid- interim guidelines extracorporeal membrane oxygenation for coronavirus disease extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease : an updated perspective of the european experience veno-venous extracorporeal membrane oxygenation support in covid- respiratory distress syndrome predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. ann intensive care calculated decisions: covid- calculators during extreme resource-limited situations first successful treatment of covid- induced refractory cardiogenic plus vasoplegic shock by combination of pvad and ecmo -a case report successful covid- rescue therapy by extracorporeal membrane oxygenation (ecmo) for respiratory failure: a case report covid- respiratory failure: targeting inflammation on vv-ecmo support a sporadic covid- pneumonia treated with extracorporeal membrane oxygenation in tokyo, japan: a case report epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study treatment of critically ill patients with covid- with convalescent plasma veno-venous extracorporeal membrane oxygenation for severe pneumonia: covid- case in japan successful treatment of covid- using extracorporeal membrane oxygenation, a case report the role of extracorporeal life support for patients with covid- : preliminary results from a statewide experience nationwide system to centralize decisions around extracorporeal membranous oxygenation use for severe covid- pneumonia in japan extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in covid- : experience with patients efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomised controlled trial extracorporeal membrane oxygenation for severe acute respiratory distress syndrome venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis extracorporeal life support organization (elso): guidelines for adult cardiac failure extracorporeal life support organization (elso): guidelines for adult respiratory failure complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of , adult patients cannulation techniques for extracorporeal life support surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) covid- : interim guidance on management pending empirical evidence. from an american thoracic society-led international task force cardiovascular collapse in covid- infection: the role of veno-arterial extracorporeal membrane oxygenation (va-ecmo) covid- and ecmo: the interplay between coagulation and inflammation-a narrative review external validation of scores proposed for estimation of survival probability of patients with severe adult respiratory distress syndrome undergoing extracorporeal membrane oxygenation therapy: a retrospective study predicting survival after ecmo for refractory cardiogenic shock: the survival after veno-arterial-ecmo (save)-score key: cord- - yjope j authors: osho, asishana a.; moonsamy, philicia; hibbert, kathryn a.; shelton, kenneth t.; trahanas, john m.; attia, rizwan q.; bloom, jordan p.; onwugbufor, michael t.; d’alessandro, david a.; villavicencio, mauricio a.; sundt, thoralf m.; crowley, jerome c.; raz, yuval; funamoto, masaki title: veno-venous extracorporeal membrane oxygenation for respiratory failure in covid- patients: early experience from a major academic medical center in north america date: - - journal: ann surg doi: . /sla. sha: doc_id: cord_uid: yjope j summary and background data: vv ecmo can be utilized as an advanced therapy in select patients with covid- respiratory failure refractory to traditional critical care management and optimal mechanical ventilation. anticipating a need for such therapies during the pandemic, our center created a targeted protocol for ecmo therapy in covid- patients that allows us to provide this life-saving therapy to our sickest patients without overburdening already stretched resources or excessively exposing healthcare staff to infection risk. methods: as a major regional referral program, we used the framework of our well-established ecmo service-line to outline specific team structures, modified patient eligibility criteria, cannulation strategies, and management protocols for the covid- ecmo program. results: during the first month of the covid- outbreak in massachusetts, patients were placed on vv ecmo for refractory hypoxemic respiratory failure. the median (interquartile range) age was years ( – ) with most patients being male ( %) and obese ( %). all cannulations were performed at the bedside in the intensive care unit in patients who had undergone a trial of rescue therapies for acute respiratory distress syndrome including lung protective ventilation, paralysis, prone positioning, and inhaled nitric oxide. at the time of this report, % ( / ) of the patients are still alive with death on ecmo, attributed to hemorrhagic stroke. % of patients ( / ) have been successfully decannulated, including that have been successfully extubated and one who was discharged from the hospital. the median duration of vv ecmo therapy for patients who have been decannulated is days ( – days). conclusions: this is the first case series describing vv ecmo outcomes in covid- patients. our initial data suggest that vv ecmo can be successfully utilized in appropriately selected covid- patients with advanced respiratory failure. t he coronavirus disease (covid- ) has demonstrated a wide range of patient presentations, ranging from asymptomatic viral colonization to acute respiratory distress syndrome (ards) requiring intubation and advanced mechanical ventilatory strategies. in cases where respiratory failure is extreme enough to preclude adequate gas exchange despite patient optimization and optimal mechanical ventilation, veno-venous extracorporeal membrane oxygenation (vv ecmo) may serve as an additional supportive therapy in our limited arsenal against covid- . this role is one that ecmo has filled in the treatment of other severe viral respiratory infections such as h n influenza , and current guidelines from the society of critical care medicine support its application in covid- . , although not a focus of this report, a small fraction of patients has presented with covid- related circulatory collapse requiring veno-arterial ecmo. there has been significant geographical variation in the use of vv ecmo for covid- . over fifty ecmo cases have been reported in japan and south korea compared to much smaller cohorts in china and italy. [ ] [ ] [ ] these discrepancies in ecmo usage are likely to be driven by differences in existing ecmo capacity and infrastructure, and variations in burden of disease and patient selection criteria across medical centers. we describe here the early experience with vv ecmo for management of covid- patients at the massachusetts general hospital, a major regional ecmo center in north america. eligibility criteria for vv-ecmo membranes result in decreased lung compliance and hypoxemia, which can be severe. during the early days of covid- in massachusetts, our center formed a covid- pandemic ecmo team consisting of cardiac and medical intensivists, pulmonologists, and cardiac surgeons that created local indications for vv ecmo in this unprecedented medical situation. a consensus was reached to offer vv ecmo to patients with severe impairment of oxygenation (p:f ratio cutoff $ - ) with respiratory instability, characterized by either periods of prolonged desaturations or elevated airway pressures despite ventilator optimization. ecmo would not be considered until it was clear that safe ventilation was not possible despite optimization of ventilator parameters by the primary medical intensive care unit (icu) team and attempted prone positioning. approval was required from the ecmo team and medical icu leadership, who had access to real time health system resource utilization statistics. several absolute contraindications to ecmo cannulation in covid- patients were identified including age > years, multisystem organ failure, active malignancy, pre-existing chronic cardiac, pulmonary (not including asthma) or hepatic disease, unknown or guarded neurologic status, and severe neutropenia (absolute neutrophil count < /mm ). body mass index (bmi) > kg/ m was stipulated as a relative contraindication given concerns about technical feasibility and achieving adequate vv ecmo flow rates in the setting of severe obesity. further, this contraindication was intended to decrease the need for multiple re-interventions for flow issues caused by body habitus that would pose a risk of significant viral exposure for providers. other relative contraindications included active bleeding, chronic renal dysfunction, immune suppression, and concurrent infection with multi-drug resistant organisms. these criteria differed from our standard non-covid ecmo criteria in a few meaningful ways including requirements for more severe respiratory failure (usual p:f ratio threshold < - ) and more stringent age and bmi limitations (usual limits of years and kg/m , respectively). currently, we are not using vv ecmo as a bridge to transplantation in covid- patients. these modifications were made in the context of known patterns of mortality and the potential for resource constraints during the covid- pandemic. notwithstanding, final criteria correlated well with guidelines released by the extracorporeal life support organization for ecmo use during the covid- pandemic. our cannulation strategy was designed to maximize efficiency to conserve limited personal protective equipment (ppe), protect healthcare staff from exposure, and minimize patients' time spent in hypoxia. given that emergency procedures inherently carry a higher risk of error and consequent exposure to covid- for the cannulating team, we make an effort to screen icu patients who may need vascular access for ecmo. fr right internal jugular and femoral vein sheaths are placed early (in the setting of impending pronation) to bypass the critical step of obtaining vascular access should ecmo become necessary. our cannulation policy provides specific guidance limiting the number of healthcare workers in the room at the time of the cannulation procedures to - icu nurses, respiratory therapists, operating room staff members, and - physicians. additional staff members wait on standby outside the patient's room, ready to assist with clinical needs that may arise. importantly, all potential members of the ecmo team received online and in-person training on the appropriate use of ppe. vv ecmo cannulation is performed at the bedside in the icu using predominantly femoral and right internal jugular cannulas. the preference for cannulation in the icu as opposed to the operating room limits provider exposure and risk of circuit mishap related to patient transport. image guidance with transthoracic echocardiography is routinely used to augment surface anatomy-based estimations of appropriate cannula positioning. avoiding transesophageal echocardiography is especially prudent during the covid- pandemic as this is considered by some to be an aerosolizing procedure. similarly, the strategy of using femoral vein and internal jugular vein cannula obviates the need for fluoroscopy to confirm cannula positioning. fluoroscopy and transesophageal echocardiography were routinely used at our center during vv-ecmo cannulations before covid- when a single cannula internal jugular vein strategy was employed (dual lumen catheter). additionally, these cannulations were most commonly performed in the operating room. our covid- protocol considers dual lumen catheters in the internal jugular vein a very distant second option, to be employed only when both femoral veins are unusable. we consider bifemoral (fem-fem) cannulation the least favorable strategy in these patients for a few reasons. first, most covid- patients in severe hypoxic respiratory failure have presented with high cardiac output and almost nonfunctioning lungs. this poses a higher risk of recirculation with a bifemoral configuration (reinfusion of oxygenated blood from the ecmo pump/oxygenator into the drainage cannula without passing through the systemic circulation) that arises due to the proximity of cannulas in this configuration. second, there are theoretical concerns about restriction in maximal flow rates with the bifemoral configuration. we have therefore reserved this approach for situations where both the subclavian and internal jugular veins are not available (eg, in the setting of pre-existing venous thrombosis). in advanced covid- related respiratory distress requiring vv ecmo, the contribution of the lungs to systemic oxygenation is truly negligible, thus necessitating very high flow rates that can only be reliably supplied by large cannulas. generally, vv ecmo flow rates should be titrated to $ - ml/kg/min to completely support systemic oxygenation. as many of the patients we encounter are overweight or obese, this translates to flow requirements of greater than l/min in many cases ( the primary function of vv ecmo is to support the patient while the lungs recover from the severe acute respiratory syndrome-coronavirus (sars-cov ) mediated cellular cytotoxic insult, permitting the use of ultra-protective lung ventilatory strategies. therapeutic anticoagulation is standard practice in the absence of bleeding concerns. patients are typically kept sedated during the duration of the ecmo run with routine monitoring of neurological status. based on early reports, we anticipated longer than usual runs on vv ecmo for covid- populations (initial reports of - days of vv ecmo for covid- patients). our standard local weaning protocols are applied, driven by improvements in gas exchange (based on routine arterial blood gas monitoring), tidal volume, and lung compliance as the lung injury resolves. attempts at decannulation are preceded by a cap trial (period of l/min ecmo sweep gas flow). when it is certain that support will no longer be needed, anticoagulation is discontinued and the ecmo system is decannulated at the bedside with hemostasis obtained via reinforced pressurizing sutures and manual pressure. following decannulation, patients are progressed steadily toward liberation from the ventilator. a comprehensive pulmonary rehabilitation program is instituted post-extubation and continues after discharge from the hospital. as of april , covid- patients with respiratory failure have been treated with vv ecmo at our institution. all patients had confirmed positive covid- rt-pcr results before time of cannulation. the median age of the cohort was years old [interquartile range (iqr) - ] and % ( / ) of patients were male. median bmi was . kg/m (iqr - ) and median body surface area was . m (iqr - ). the most common co-morbidities were diabetes mellitus ( / , %) and obesity ( / , %). no patients had co-occurring influenza or respiratory syncytial virus. patients were intubated early in their admission and the median time from admission to ecmo cannulation was . days (iqr . - . ). sixty-seven percent ( / ) of patients were transferred to us from outside institutions; however, all patients were cannulated with ecmo at our institution. all patients had undergone a trial of paralytic, prone positioning, and inhaled nitric oxide before ecmo cannulation. all patients had received a -day course of hydroxychloroquine during their hospitalization (table ) . all patients were cannulated at the bedside in the icu with or fr cannulas in the right internal jugular vein and fr cannulas in the right femoral vein. patients have required high flow rates (range . - . l/min) and displayed high plateau pressures (range - cm h ) during the ecmo run (table ) . thus far, % ( / ) of patients have successfully survived ecmo decannulation. two of these patients have also been extubated, and was discharged from the hospital after negative covid- rt-pcr tests. the median duration on ecmo for those who survived to decannulation was days ( - days). one patient died on day of his ecmo run after withdrawal of support due to declining neurologic status secondary to a hemorrhagic in one of the first case series describing vv ecmo in severe covid- related respiratory failure, we highlight outcomes from the first month of the pandemic at a major academic center in north america. our program has supported several carefully selected covid- patients to recovery, providing preliminary support for the role of vv ecmo in this pandemic. these initial results are an improvement from early international reports on ecmo use in covid- patients where mortality rates were described to be as high as % with a range of - days on the circuit for patient who made it to decannulation. it is notable that we are an established ecmo center, with longstanding experience treating patients with ards and highly experienced intensivists, respiratory therapists, nurses, and surgeons. given increased care needs, exposure risks to health care staff are higher in ecmo patients, necessitating higher usage of ppe. facing this new reality has been greatly facilitated by the commitment of our health system leadership to providing the training and equipment needed to protect team members. these data are still very preliminary for this small cohort and long-term outcomes for covid- vv ecmo patients remain unknown. our optimism is tempered by a realistic appreciation for the comparative burden of providing vv ecmo for such long periods. ecmo is resource intensive and can impose strains on the infrastructural, human, and emotional capital of the hospital. the role of a regularly convening ecmo leadership team toward mitigating these tolls cannot be over-emphasized. decisions for ongoing ecmo use must be made in the context of relative resource reserve and dynamic consideration of continued ability to address needs throughout the hospital. indeed, there is a potential scenario where the health system is overwhelmed and ecmo must be abandoned to allow provision of basic services to more patients. however, in the absence of such extreme constraints, vv ecmo remains a fundamental rescue strategy for appropriately selected patients with severe ards due to covid- , and this early report demonstrates its feasibility and potential benefits. extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ) initial elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure extracorporeal membrane oxygenation for coronavirus disease clinical features of patients infected with novel coronavirus in wuhan ecmo for ards due to covid- cannulation strategies in adult veno-arterial and veno-venous extracorporeal membrane oxygenation: techniques, limitations, and special considerations key: cord- -tmplwyz authors: uemura, tatsuki; matsuda, wataru; ogawa, tatsunori title: concerns about the timing and settings of initiating extracorporeal membrane oxygenation in patients with severe coronavirus disease pneumonia date: - - journal: crit care med doi: . /ccm. sha: doc_id: cord_uid: tmplwyz nan w e read with great interest the clinical investigation reported by yang et al ( ) published in a recent issue of critical care medicine. the authors describe the characteristics of patients with acute respiratory distress syndrome (ards) induced by the novel coronavirus disease (covid- ) requiring extracorporeal membrane oxygenation (ecmo). they reported the mortality rate of covid- -induced ards requiring ecmo as . %, which is similar to the . % reported for outcomes (death or coma) in another case series ( ) . they also described the timing of initiation and the initial settings of ecmo in patients with severe ards induced by covid- . we would like to discuss whether the strategy they reported can be considered as standard for ecmo treatment for severe covid- pneumonia. first, regarding the timing of initiating ecmo, the authors state that earlier initiation after mechanical ventilation may be associated with improved outcomes. although early initiation is reported to be associated with good prognosis in adult ards patients ( ), covid- pneumonia is reported to present with features different from typical ards ( ). would different phenotypes of respiratory failure require different ecmo treatment strategies? we are still doubtful whether early initiation of ecmo can be considered similarly for typical ards and covid- pneumonia. addressing this will require comparisons between early initiation and late initiation groups. second, the initial setting of ecmo in the study by yang et al ( ) seems to be unique. the authors report that many patients developed bradycardia while the centrifugal pump was on. this raises the question of whether this phenomenon is unique to covid- pneumonia. looking at the many covid- case series reported to date, we find no descriptions of bradycardia elsewhere. to avoid bradycardia, the authors suggest increasing ecmo pump rotation slowly from , revolutions per minute (rpm) to the target rotation at increments of rpm every minutes. we speculate venovenous ecmo does not, in fact, have a significant effect on hemodynamics when initiating ecmo as long as a sufficient intravascular volume is maintained. another report of patients with covid- pneumonia requiring ecmo also described gradually increasing the rotation speed of the centrifugal pump when starting ecmo ( ), but at a seemingly faster rate than yang et al ( ) reported. we question then whether it is actually possible to prevent bradycardia using the authors' method. finally, have the laboratory test values presented for survivors and nonsurvivors in table in ( ) mistakenly been switched, given that the authors state that "survivors had a significant lower creatinine than nonsurvivors prior to ecmo"; the numbers in table in ( ) are reversed. we are still in the pandemic phase of covid- , and thus, appropriate indications and methods for initiating ecmo support in critically ill patients with covid- pneumonia are important to establish. the authors have disclosed that they do not have any potential conflicts of interest. extracorporeal membrane oxygenation for coronavirus disease -induced acute respiratory distress syndrome: a multicenter descriptive study prognosis when using extracorporeal membrane oxygenation (ecmo) for critically ill covid- patients in china: a retrospective case series extracorporeal life support for adult patients with severe respiratory failure covid- pneumonia: different respiratory treatments for different phenotypes? extracorporeal membrane oxygenation for coronavirus disease key: cord- -g gt oh authors: li, tong; yin, peng-fei; li, ang; shen, maxwell r.; yao, yong-xing title: acute respiratory distress syndrome treated with awake extracorporeal membrane oxygenation in a patient with covid- pneumonia date: - - journal: j cardiothorac vasc anesth doi: . /j.jvca. . . sha: doc_id: cord_uid: g gt oh nan since the first outbreak of coronavirus disease in december , which was caused by severe acute respiratory syndrome coronavirus (sars-cov- ), the disease has spread worldwide over the past months and become a globle pandemic. although most infections are mild, severe impairment of the respiratory system and acute respiratory distress syndrome (ards) may develop in patients with pre-existing comorbidities such as hypertension, diabetes, and other lung diseases. extensive use of mechanical respiratory support and extracorporeal membrane oxygenation (ecmo) has helped to reduce the case fatality rate of covid- to less than % in some regions. however, various related complications, including pneumothorax, thrombosis, ventilator-associated infection, ventilator-induced lung injury, systemic inflammation, and neurological complications may emerge during the use of conventional mechanically ventilated ecmo. in recent years, ecmo without mechanical ventilation (mv) and sedation (awake ecmo) has been utilized in several subset populations. similar to conventional ecmo, awake ecmo also notablely improves oxygenation; awake ecmo exempts mv and avoids the complications associated with prolonged sedation and tracheal intubation. awake and fully mobile ecmo have proven to be beneficial in patients with ards induced by pneumocystis pneumonia, immunocompromised patients, and patients requiring extracorporeal life support. [ ] [ ] [ ] however, the use of awake ecmo has not been reported in ards patients secondary to covid- pneumonia. in our case report, we managed a case of ards resulting from covid- pneumonia with awake ecmo. an -year-old female patient was admitted to our intensive care unit for severe bilateral pneumonia. thoracic radiography showed diffuse whiteout of the lungs, and computed tomography (ct) showed bilateral multiple ground glass opacities ( figure. a, b). her main symptoms were persistent fever, cough, and shortness of breath for seven days. her laboratory tests indicated a c-reactive protein concentration of . mg/dl, with a normal coagulation profile (d-dimer, µg/l) and serum enzyme levels. a complete blood count revealed leukocytosis ( , /dl), with neutrophil predominance ( . %) and a low lymphocyte count ( /dl). the nasal and pharyngeal swab specimens tested positive for covid- and negative for influenza a and b viruses, adenovirus, respiratory syncytial virus, and parainfluenza virus , , and . initial arterial blood gas (abg) analysis was performed, which showed a ph of . , partial pressure of arterial oxygen (pao ) of . mmhg, partial pressure of arterial co (paco ) of . mmhg, and a low pao /fio ratio with a fio of %. high-flow oxygen therapy via the nasal cannula under a mask was initiated with the goal of maintaining her oxygen saturation (spo ) above %. in an isolated room, the patient received intensive monitoring, antiviral therapy (arbidol . formation. an intravenous infusion of norepinephrine ( µg/min) was titrated to maintain a stable blood pressure. two hours later, she regained consciousness. she was hemodynamically stable, and norepinephrine was discontinued. the abg analysis showed the following: paco , . mmhg; pao , . mmhg (pao /fio = ). after a comprehensive evaluation, she was extubated and received awake ecmo support. the flow rate was adjusted to ml/kg/min, with air flow/blood flow of . to : . after extubation, the patient was not breathless and had an rr of breaths/min. she was in a good mental state and could feed herself. she received plasma ( ml) from a convalescent donor who recovered from covid- , and two days later, her covid- test result was negative. her blood test showed a hemoglobin level of . g/dl; thus, packed red blood cells ( ml) were administered. after days of ecmo support, the patient's pulmonary function improved. her abg analysis showed the following: pao , mmhg (fio , %); paco , mmhg; and spo , %. her temperature was normal, with a heart rate of beats/min and an rr of breaths/min. thoracic ct demonstrated a significant improvement in ground glass opacification from her previous scan (figure. d ). based on her condition, the weaning process began while maintaining continuous assessment. the patient tolerated weaning well with a gradual reduction in the ecmo blood flow rate. on complete suspension, her abg analysis showed the following: pao , mmhg (fio , %); paco , mmhg; spo , % with stable hemodynamic parameters (blood pressure: / mmhg, heart rate: beats per minute). the patient was successfully weaned off ecmo and recuperated under supportive care. the subsequent therapy period was uneventful. she was discharged from the hospital after days of additional therapy with abg analysis showing a paco of mmhg and pao of mmhg with fio of %. covid- is an emerging, rapidly evolving pandemic. profound hypoxemia and acute lung failure, the main causes of death, are the prominent features of ards resulting in a subset of critical covid- pneumonia patients. despite the wide use of mv, the mortality rate is as high as % in intubated populations. ecmo has become an alternative therapy for prolonging patient life and allowing time for lung recovery, especially in severe ards resulting from covid- . - however, conventional ecmo is conducted under mv and sedation; various complications may emerge during prolonged mv and sedation, including pneumothorax, increased risk of infection, ventilator-induced lung injury, systemic inflammation, and neurological complications. [ ] [ ] in addition, pneumonia and ards caused by covid- show an unusual pattern of disease progression. lung inflammation and tissue destruction arise from the lower airways and involve the alveoli, and features of pulmonary edema and hyaline membrane formation cause a restrictive lung pattern. in recent years, awake ecmo has been used in selected cases of ards and has proved advantageous. the strong rationale for using awake ecmo over conventional mechanically ventilated ecmo is that awake ecmo avoids intubation and mv, results in minimal stress, has no synchronization issues, and requires no sedatives. these parameters help avoid complications such as ventilator-induced lung injury, ventilator-associated infections, and delirium secondary to prolonged sedative usage. while providing time for lung recovery, awake ecmo permits spontaneous breathing, self-feeding, and active functional rehabilitation, which are all essential for post-ecmo recuperation. in our case, the premature extubation caused the gradual deterioration of pulmonary function, suggesting that inflammation persisted even after four days of respiratory support. the indications to initiate ecmo in covid- have been suggested in a previous publication; namely, pao /fio of < mm hg for three hours or more, pao /fio < mm hg for six hours or more, or an arterial ph of less than . with a paco of ≥ mmhg for hours. in the present case, after re-intubation and respiratory support for hours, profound hypoxemia was still evident, which prompted the initiation of v-v ecmo. subsequently, an awake ecmo strategy was adopted. after extubation, the patient was able to communicate with her relatives and medical staff, and to feed herself the following day. throughout the duration of her treatment under awake ecmo, early physiotherapy was initiated with passive and active movements progressing to daily ambulation without obvious discomfort. alongside, preventive strategies and class iii precautions as recommended for ecmo in covid- were followed. the medical team donned face shields and disposable drapes in addition to the surgical masks and gloves, as recommended by the chinese society of anesthesiology. clinical predictors of mortality due to covid- based on an analysis of data of patients from wuhan, china clinical characteristics of coronavirus disease in china extracorporeal membrane oxygenation for severe acute respiratory distress syndrome awake" extracorporeal membrane oxygenation (ecmo): pathophysiology, technical considerations, and clinical pioneering better be awake"-a role for awake extracorporeal membrane oxygenation in acute respiratory distress syndrome due to pneumocystis pneumonia six-month outcome of immunocompromised patients with severe acute respiratory distress syndrome rescued by extracorporeal membrane oxygenation. an international multicenter retrospective study awake and fully mobile patients on cardiac extracorporeal life support clinical course and outcomes of critically ill patients with sars cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study covid- , ecmo, and lymphopenia: a word of caution extracorporeal membrane oxygenation -crucial considerations during the coronavirus crisis contemporary approaches in the use of extracorporeal membrane oxygenation to support patients waiting for lung transplantation clinical management of venoarterial extracorporeal membrane oxygenation pathological findings of covid- associated with acute respiratory distress syndrome extracorporeal membrane oxygenation during the coronavirus disease pandemic anesthesia considerations and infection precautions for trauma and acute care cases during the covid- pandemic: recommendations from a task force of the chinese society of anesthesiology the use of awake ecmo in critically ill patients who respond poorly to mv may be a promising therapeutic strategy for managing patients with ards due to covid- pneumonia. however, this warrants further investigation. the authors have no conflicts of interest to disclose. informed consents were obtained for publishing the details of the report and the photograph. key: cord- -d v xtx authors: li, rui; qiao, songlin; zhang, gaiping title: analysis of angiotensin-converting enzyme (ace ) from different species sheds some light on cross-species receptor usage of a novel coronavirus -ncov date: - - journal: journal of infection doi: . /j.jinf. . . sha: doc_id: cord_uid: d v xtx nan a novel coronavirus from wuhan in central china, named -ncov, has recently caused an epidemic of pneumonia in humans and posed a huge threat to global public health. , to the date / / , -ncov has led to more than , confirmed cases and deaths in china according to national health commission of the people's republic of china ( http://en.nhc.gov. cn/index.html ). cases have also been documented in a growing number of other international locations, including the united states ( https://www.cdc.gov/coronavirus/ -ncov/index.html ). as a consequence, it is urgent to develop effective measures to control this novel coronavirus on the basis of its pathogenesis. host receptor recognition is a determinant for virus infection. during the time of this letter preparation, three works have just been published to explore the receptor usage of -ncov. a work by zheng-li shi et al. has shown that angiotensin-converting enzyme (ace ), the receptor for severe acute respiratory syndrome coronavirus (sars-cov), from human, rhinolophus sinicus bat, civet, swine but not mouse mediate -ncov infection in vitro , while the detailed mechanisms are not yet determined. the other two works have reported or predicted human ace usage of -ncov in a similar way to sars-cov mainly based on the coronavirus spike (s) glycoproteins. , considering the fact that the s proteins mutate and gain capability to recognize host receptors among species, , there is still a lack of analyses on receptor usage of -ncov from the receptor perspective, which does not evolve as quickly as viruses. here, we firstly performed amino acid sequence alignment of ace from different species, including human, five non-human primates (gibbon, green monkey, macaque, orangutan and chimpanzee), two companion animals (cat and dog), six domestic animals (bovine, sheep, goat, swine, horse and chicken), three wild animals (ferret, civet and chinese horseshoe bat) and two rodents (mouse and rat). the alignment by clustal w . shows that they share a high sequence similarity except chicken (data not shown). the result suggests that -ncov of probable bat origin may not interact with chicken ace and subsequently infect them, which were not considered in the following analyses. in ace , the regions at position - , - and - are demonstrated to be involved in the interaction with sars-cov s protein, where the residues at positions , , , and are critical. therefore, we took a close comparison in these regions and residues. as shown in fig. , human and non-human primates share the identity sequences in the regions and residues, implying that ace from non-human primates may recognize -ncov and medi-ate its infection. as a result, non-human primates may be susceptible to -ncov and serve as animal models for antiviral research or intermediate hosts for cross-species transmission. in fig. , the residues of most companion, domestic and wild animals are conserved, especially for the critical ones stated above, while certain ones are variable. for example, lys , glu , asp/glu and lys are conserved, which probably form salt bridges. interestingly, the changes at positions , and are observed. these changes suggest steric hindrance and electrostatic interference for host-virus interaction. taking civet ace as an example, the change of lys to thr is likely to form a hydrogen bond instead of a salt bridge. in addition, the polar side chain of thr may influence the hydrophobic interaction of the original met . all these changes may result in a lower binding affinity. however, an additional region covering residues - has been shown to be involved in civet ace binding to sars-cov and enhance their interaction. consequently, we can't preclude the existence of other regions to compensate for the residue changes. with most residues in human ace , the ones from these compaion, domestic and wild animals may be favorable for -ncov recognition, which is in consistent with the recent work by zheng-li shi et al. in case cross-species transmission, close contact with sick or asymptomatic companion, domestic and wild animals should be cautious, such as for workers in livestock farming and travellers in the wild. in contrast, certain significant changes occur in the mouse and/or rat ace compared to the human one ( fig. ) . the asn and ser in mouse ace may not form favorable interactions with -ncov due to their electrostatic or hydrophilic characteristics. importantly, the change into his in both mouse and rat ace does not form a strong salt bridge as lys does. since the structural information for mouse and rat ace is unavailable, we carried out homology modeling using human ace (pdb code ajf) as template on online ( https://swissmodel.expasy.org ) for further analyses. in fig. a, the change into ser in mouse ace may interfere with the hydrophobic interaction of the original met . additionally, the changes into asn and his definitely affect the salt bridge formation and electrostatic potential. the change into his in rat ace is similar in the effect on receptor-virus interaction ( fig. b) . these analyses partially explain why mouse ace does not mediate -ncov infection reported by zheng-li shi et al. and assume that rodents are not likely to be the susceptible host. in conclusion, we conducted sequence and structural analyses of angiotensin-converting enzyme (ace ) from different species, which sheds some light on cross-species receptor usage of -ncov. all these analyses raise an alert on a potential interspecies transmission of -ncov and propose further surveillance in other animal populations. structural studies on human and other species ace in complex with -ncov spike protein will con- the authors declare no conflict of interest. very recently, a letter in journal of infection reported the outbreak of the novel cornonavirus from dec. in china, especially in hubei province. this novel cornonavirus may originate from the bat, is just named as the covid- by the world health organization (who). the covid- outbroke from wuhan, the capital of hubei province, has spread to other provinces of china and even other countries. strong human-to-human transmission is established. until feb. , , there have been cases of covid- infections confirmed in mainland china, including deaths. to prevent and control the spread of the epidemic, many strategies are needed. predicting the trend of the epidemic are quite important to the allocation of medical resources, the arrangement of production activities, and even the domestic economic development all over china. therefore, it is very urgent to use the latest data to establish an efficient and highly suitable epidemic analysis and prediction model according to the actual situation, and then to give reliable predictions, which could provide an important refer-ence for the government to formulate emergency macroeconomic decisions and medical resources allocation. recently, the susceptible-exposed-infectious-recovered (seir) or other similar models , are used to forecast the potential domestic and international spread of this covid- epidemic with parameters estimated from other sources.the real situation could be much more complicated and changing all the time. especially, with the implementation of the chinese government's multiple epidemic control policies, the control of nationwide epidemic has become obvious. however, the medical supplies in hubei will still affect the implementation of national policies. in this letter, we present the current situation of the epidemic, predict the ongoing trend with data driven analysis, and estimate the outbreak size of the covid- in both hubei and other areas in mainland china. the data of the epidemic are listed in table and also graphically shown in fig. , in which "china" is used to denote the mainland china, and "other" mainland china other than hubei province. the data includes the daily confirmed(suspected) infections, totally confirmed(suspected) infections, daily deaths, and total deaths from jan. , to feb. , , reported by the national health commission of the republic of china (nhc), , and health commission of hubei province (hch). jan. , , containing all the cases reported from to , is the zeroth day in this letter, and then others are implied. the total number of suspected cases reaches the peak value on the th day (feb. ), and then drops rapidly. notice that, until feb. , , almost all the cases of deaths ( / , %,) locates in hubei province, which reveals the epidemic in hubei is much more serious than that in the other areas of china. on the hand, it states the strict quarantine and limitation on population mobility have effectively prevented outbreaks in other provinces of china. scribe the data of daily infections and deaths in hubei, where x = (t + . − t t ) with t denoting the day, and t t representing the turning point; a and k are the parameters and determined by the data together with t t . the cumulative data of infections or deaths are obtained by the integration over h ( t ). for the epidemic in the other areas of china, the data of infections shows an asymmetric character, and then will be described as where x = t − t t ; the parameters b, k , and k together with t t , are then determined by fitting to the data. fig. shows the fit and trend predictions to the total infections and deaths in hubei and china other than hubei. the extracted turning point of the infections in hubei is the th day, namely, feb. , . the epidemic in hubei is predicted to end after mar. , . we estimated that the epidemic is to end up with a total of , infections in hubei, not including the clinically diagnosed cases since feb. , which may enlarge the prediction by . times. with considered data, namely, data from jan. to feb. , the average errors are bout and for the fits to describe the daily and cumulative infections in hubei, respectively, corresponding to . % and . % for the average relative errors, respectively. fig. (b) and (e) shows the estimations of the total and daily deaths in hubei. the predicted turning point is feb. , . the total deaths is estimated to be . notice the distribution of the daily deaths is delayed about ∼ days compared with the that of the daily infections. the average errors are bout and for the model to describe the daily and cumulative death numbers, respectively, corresponding to the relative errors . % and . %, respectively. the numbers of the daily and total infections in china other than hubei are showed in fig. (c) and (f), respectively. the extracted turning point is feb. , and the epidemic is expected to end on the th day, namely, on mar. , . the estimated number of cumulative infections is about , in china other table the data of epidemic caused by the covid- pneumonia in the mainland china and hubei, including (a) daily infections, (b) daily deaths, (c) total infections, (d) total deaths, (e) daily and (f) total suspected cases. china hubei a b c d e f a b c d / / / / / / / / / / / / / / / / / / / / , fig. (f)), we did not parameterize this data, and hence did not give a trend prediction. the covid- epidemic in china is predicted to end after mar. , , and cause , - , infections and about deaths. however, the data trends show that the quick and active strategies to reduce human exposure taken in china, such as limi-tation on population mobility and interpersonal contact rates, strict quarantine on migrants, have already had good impacts on control of the epidemic. now the outbreak and deaths of the covid- epidemic are mainly in hubei province. after this letter has been written, the hubei reported , confirmed infections (including , clinically diagnosed cases) on feb. , , which is almost times greater than the data of the previous day. the huge fluctuation is due to the changing of diagnostic criteria in hubei. and this clinical criteria taken in hubei is expected to play an active and important role in controlling the outbreak and death rate. the authors declare no conflict of interest. dear editor , recently, several studies in this journal have highlighted the threat of avian influenza virus (aiv) to humans, poultry, and other animals. [ ] [ ] [ ] [ ] [ ] [ ] in equines, there was only one reported influenza outbreak caused by aiv, which occurred in - in china. however, aiv still poses a potential threat to equines. in contrast to aiv, equine influenza virus (eiv) is a commonly known causative pathogen of acute respiratory disease in equines. to date, two subtypes of eivs have been determined in the equine population worldwide: h n and h n . h n eiv was initially identified in prague in , and the last outbreak caused by h n eiv occurred in . h n eiv was first isolated in miami in and is currently responsible for ei outbreaks worldwide. during continuous transmission and evolution in equines, h n eiv strains diverged genetically into three distinct lineages: predivergent, european, and american. historically, there have been four main ei outbreaks in mainland china, occurring in china, occurring in , china, occurring in - china, occurring in , , and - . in the first, third, and fourth outbreaks, the isolated eiv strains were of the h n subtype, h n subtype european lineage, and h n subtype american lineage, respectively. in the second ei outbreak, the causative pathogen (a/equine/jilin/ / ) was determined to be h n subtype influenza a virus (iav) by antigenicity characterization. however, after genetic sequencing, all eight segments of a/equine/jilin/ / were genetically closer to those of avian influenza virus than those of eiv, indicating an interspecies transmission event. the - ei outbreaks in china contain two major outbreaks. the first ei outbreak occurred in jilin and heilongjiang provinces between march and june , with a morbidity of % and a mortality of up to % in some herds. the second ei outbreak occurred in heilongjiang province in april , with a morbidity of % and no mortality. the high mortality and unique antigenicity of a/equine/jilin/ / attracted the attention of eiv researchers. however, after the - ei outbreaks in china, the virus disappeared from the equine population for unknown reasons. although no evidence in the epidemiological investigation worldwide supports the continuous circulation of a/equine/jilin/ / -like eiv in equines, we should not underestimate the potential of interspecies aiv transmission to equines and the possibility of future ei outbreaks caused by aiv. the haemagglutinin (ha) of iavs recognizes and binds the cell surface sialic acid (sa) receptor of the host respiratory tract, and then the virus enters into cells and replicates. the distribution of the sa receptor influences the host range of iavs. human influenza viruses preferentially bind the saa , gal receptor, while aivs preferentially bind the saa , gal receptor. it has been reported that the saa , gal receptor is abundant in the epithelial cells of the horse trachea, and animal experiments indicate that iavs with an ha recognizing the saa , gal receptor could replicate in horses. this finding provides a prerequisite for cross-species transmission of aiv to equines. in fact, there were several pieces of direct molecular evidence supporting the interspecies transmission of aiv to equines, in addition to the - ei outbreaks in china. in , abdel-moneim et al. reported one h n eiv strain (a/equine/egypt/ av / ) isolated from donkeys with cough, fever and serous nasal discharge in egypt. sequencing results indicated that the virus had a close genetic relatedness to h n aiv. in addition, h seroconversion was observed in . % ( / ) of the examined donkeys. in , he collected equine lung tissue samples in china and isolated one aiv-derived h n eiv strain (a/equine/guangxi/ / ) ( https://kns.cnki.net/ kcms/detail/detail.aspx?dbcode=cmfd&dbname=cmfd & filename= .nh&v=mtmxmzc ck wrji sexleedove x wkviuelsogvymux efltn romvqzcvryv xrnjdvvjmt vazvpt rknua u= ). among the tested equine serum samples in china, . % ( / ) of samples were positive for anti-h n antibody. in the - ei outbreaks in pakistan, khana et al. reported that the isolated eiv strain (a/equine/pakistan/ ) was reassorted from aiv. the common characteristic for the reported cross-species transmission events of aiv to equines in china, pakistan, and egypt is that they occur in farming equines. , in the mixed farming system, equines and domestic poultry often live in close proximity. compared with racehorses, farming equines have more opportunities to contact domestic poultry and experience long-term environmental exposure to poultry. aiv infections in poultry increase exposure risks to equines. recently, frequent reports of cross-species transmission events of aiv to farming dogs in china and korea also indicate the potential threat of aiv to farming animals with close contact with poultry. another problem is that the farming equines in china, pakistan, and egypt had no vaccination history. even in some racehorse populations, vaccinations for eiv are not routinely performed as recommended by the world organization for animal health (oie) expert surveillance panel on ei vaccine composition. although h n eiv is antigenically distinct from a/equine/jilin/ / , animal experiments indicated that high doses of ei vaccines still provided complete protection against challenge with a/equine/jilin/ / . accordingly, routine vaccination with h n ei vaccines in equines might prevent aiv infection to some degree, at least for h n subtype aiv. several strategies may help reduce the threat of aiv to equines, including reducing exposure of equines to poultry, birds, and other hosts of iav, especially animals with clinical signs of influenza virus infection; monitoring aiv prevalence in domestic poultry around equines and routinely vaccinating domestic poultry with aiv vaccines; vaccinating susceptible equines with ei vaccines, especially farming equines in close contact with domestic poultry; and monitoring the prevalence of multiple aiv subtypes in equines, not merely that of those restricted to h n subtype. none. we read with interest recent articles in this journal regarding the utility of next-generation sequencing for the diagnosis bacterial meningitis. , bacterial meningitis causes substantial morbidity and mortality worldwide. rapid identification of the microorganisms is essential for early initiation of appropriate antimicrobial therapy, thereby improving clinical outcome. yet routine diagnostic methods fail to identify the bacteria in the majority of patients. over the last decade, advanced sequencing technologies have greatly improved our capacity to detect the causative agents of infectious diseases in clinical samples. , of these, the single molecule real-time sequencing developed by oxford nanopore technologies (ont) is a promising tool for diagnostic setting because of its short turnaround time. in late april , a -year old seller of fish-noodles was referred to our hospital with a -day history of headache, fever and vomiting. he had a history of heavy alcohol use and hepatitis c infection, and had cirrhosis and diabetes mellitus. on admission, he was unconsciousness (a glasgow coma scale of ), with a body temperature of °c, a blood pressure of / mmhg and neck stiffness. initial gram-stain and microscopy of csf showed grampositive cocci, white cells/ul with % neutrophils, elevated protein and low glucose level, and high lactate concentration ( fig. a) . routine bacterial culture, plus streptococcus pneumoniae and s. suis pcrs were all negative. he was diagnosed with bacterial meningitis, and given a combination of ceftriaxone ( g/ h) and dexamethasone ( . mg/kg/ h). his clinical condition steadily improved. his second and third csf samples became negative by gram stain. the other csf parameters also improved, except the glucose, which remained low ( fig. a) . on day of hospitalization, the patient suddenly became unconsciousness with fever. brain magnetic resonance imaging showed bifrontal abscesses ( fig. b) . after consulting a local neurosurgeon, aspiration of the brain abscesses was not advised and the patient was treated empirically with meropenem ( g/ h) and vancomycin ( g/ h). due to continued diagnostic uncertainty, we performed s rrna sequencing of the admission csf, stored as part of an going clinical study (supplementary materials), using an established sangersequencing based s rrna method. subsequently, analysis of the obtained sequences revealed evidence of s. agalactiae (supplementary figure ). given this new diagnostic result of the admission csf and because the patient had recovered clinically, the patient was given million units of penicillin g for every h. after day of hospitalization, all csf parameters had normalised ( fig. a) . likewise, on ct scan the brain abscess was now significantly improved ( fig. c) . the patient was discharged with full clinical recovery. additionally, minion sequencing of complete s rrna gene was retrospectively carried out on the extracted nucleic acid of the admission csf yielded a total of , reads after min of sequencing run. of these, , reads ( %) were successfully aligned to s. agalactiae ( fig. d) . the remaining reads were assigned to other streptococcus species (mostly s. dysgalacticiae ( n = . , %)), likely attributed to a combination of the high level of sequence similarities of the s rrna region between them and the sequencing errors introduced by the minion systems. analysis of sequencing data generated during the , and min of sequencing run time also yielded the same results (supplementary figure ). details about the minion procedure are presented in supplementary materials. to further assess of the utility of csf minion sequencing of s rrna gene for the detection of bacterial meningitis pathogens, six csf samples from patients with confirmed bacterial meningitis enrolled in the abovementioned clinical study were tested ( table ) . analysis of the minion reads obtained after two hours of the sequencing run showed that the majority of reads were correctly assigned to the corresponding bacterial species ( s. pneumoniae and s. suis) or genus ( neisseria ) found in the csf samples by diagnostic work up of the clinical study ( fig. e and table ). additional analysis of the obtained reads generated at two earlier time points ( min and min) of the sequencing run generated the same results ( table ) . collectively, we report the first application of minion sequencing of s rrna gene to detect bacterial meningitis causing pathogens in csf samples from a low and middle-income country. the assay was able to detect the bacterial causes in all of the seven tested csf samples. meanwhile, gram stain and culture, the two most commonly used methods in clinical microbiology laboratories worldwide, were negative in / samples. ( fig. and table ). in addition to csf samples described in the present study and a recent pilot study from korea, successful detections of haemophilus influenzae in sputum and campylobacter fetus in culture materials by minion sequencing of s rrna have recently been reported. together, the data suggest that minion sequencing of s rrna is a sensitive method for rapid and accurate detection of pan-bacterial pathogens, including unexpected microorganisms, in clinical samples. additionally, the bacterial species information generated by the analysis of s rrna sequences can be useful for disease surveillance and vaccine evaluation. thus, the application of the method would be relevant for both patient management and epidemiological research. indeed, to the best of our knowledge the present study represents the first report of s. agalactiae associated meningitis in vietnam. because the incidence of invasive diseases (including meningitis) caused by s. agalactiae has been reported with increased frequency in recent years, s. agalactiae should be considered as an important differential owing to the unavailability of the reagents at the time of patient admission, we were not able to perform real-time diagnosis using minion sequencing on the collected csf samples. however, same day diagnosis is theoretically achievable, because the current workflow takes - h to operate. prospective study is urgently needed to assess its translational potential in the diagnosis of bacterial meningitis. since september , a prospective observational study aiming at exploring the utility potential of next-generation sequencing in patients presenting with central nervous system (cns) infections has been conducted in the brain infection ward of the hospital for tropical diseases (htd) in ho chi minh city, vietnam. htd is a tertiary referral hospital for patients with infectious diseases from southern provinces of vietnam, serving a population of > million. any patient ( ≥ years) with an indication for lumbar puncture was eligible for enrolment. patient was excluded if no written informed consent was obtained. as per the study protocol, csf, plasma and urine samples were collected at presentation alongside demographic, meta-clinical data and results of routine diagnosis. after collection, all clinical specimens were stored at − °c until analysis. the clinical study received approvals from the institutional review board of the htd and the oxford tropical research ethics committee of the university of oxford. written informed consent was obtained from each study participant or relative (if the patient was unconsciousness). sequencing of complete s rrna gene was retrospectively performed using minion nanopore sequencer (ont), following the manufacturer's instructions. in brief, amplification of the complete s rrna gene and library preparation were carried out on extracted nucleic acid using s barcoding kit (sqk-rab , ont) and primers ( f -agagtttgatcctggctcag- and r -ggttaccttgttacgactt- ), followed by the sequencing of the amplified product using r . flow cells (ont). minion reads were first basecalled using albacore v . . (ont), followed by demultiplexing using porechop ( https://github.com/rrwick/porechop ). determination of bacterial genus/species composition in the obtained reads was then carried out using epi me interface (metrichor, oxford, uk), a platform for cloud-based analysis of minion data. overall, the whole procedure of minion sequencing of s rrna gene takes - h to complete (supplementary figure ) . we, the author of the submitted manuscript declare that we do not have a commercial or other association that might pose a conflict of interest (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding). dear editor, several aspects of influenza have been highlighted recently, including its global, comparative seasonality, and issues around rapid point-of-care testing. in addition, the uk has a national surveillance programme, the uk severe influenza surveillance system (usiss) to monitor and investigate severe cases of influenza across the country, including severe cases of influenza admitted to intensive care (icu) and high dependency units (hdu). specifically, the aim of this latter arm was to "monitor and estimate the impact of seasonal influenza on the population" and to "describe the epidemiology of severe disease." this surveillance began in the - influenza season and has continued to the present, with mandatory participation by all nhs trusts. leicester is one of nhs commissioned centres in the uk providing extra-corporeal membrane oxygenation (ecmo) support for severe acute respiratory failure in adults. this process involves draining deoxygenated venous blood from the superior and inferior vena cavae, pumping this blood through a membrane lung, where oxygenation and carbon dioxide elimination take place. oxygenated blood is delivered back into the right atrium, therefore replacing the function of the native lung. in this way, ecmo can be used to support patients with respiratory failure of any cause. acceptance for admission for ecmo support follows referral to the ecmo service via structured questionnaire and discussion with the ecmo consultant on-call. patients are commenced on ecmo where benefits are deemed to outweigh the risks in patients with potentially reversible respiratory failure, who are already on maximal conventional therapy at their referring centre, and who are not achieving lung protective ventilation. here, as part of our national usiss role, we describe severe influenza cases that required ecmo support in whom the predominant indications were severe hypoxia with a pao :fio ratio of < despite maximal conventional therapy, and/or hypercapnoeic respiratory failure with a ph < . despite ventilation pressures > cm h o. during the - influenza season cases of severe influenza were admitted to glenfield hospital for ecmo from our referring centres. most were male ( / , . %, - years, bmi: - ; female / , - years, bmi: - ), and of white british ethnicity ( / , . %; with each of chinese, asian, african ethnicity). comorbidities included, obesity, hypertension, asthma, copd, diabetes, anxiety, depression, epilepsy, a history of smoking and alcohol use (or abuse). all cases except for one influenza a(h n ) infection (possibly two as subtyping was not performed for another sample) were due to influenza a(h n )pdm . only one case had a history of influenza vaccination. various 'on referral' ecmo-related parameters were extracted, as well as contemporaneous laboratory results. these were statistically compared between patients who died ( n = ) and those who survived using t -test or mann-whitney test for continuous variables and fisherexact test for categorical variables. correlation between duration on ecmo and laboratory parameters was assessed using spearman's rank correlation coefficient. ( n = ) ( tables and ) . surprisingly, it was found that on direct comparison, most of the referral parameters for patients starting ecmo were not statistically different between those influenza-infected patients that eventually survived ( n = ) versus those who died ( n = ) -a case fatality rate of %. one patient was dropped from this analysis due to some missing data. only the respiratory rate (rr, p = . ) and the lactate ( p = . ) showed statistically significant differences between the two groups, with higher values being found in the patients who ecmo -extra-corporeal membrane oxygenation; sofa -sequential organ failure assessment; peep -positive end expiratory pressure; h o -water; bpm -breaths per minute; pao /paco -partial pressure of arterial oxygen/carbon dioxide; altalanine aminotransferase. * rank correlation coefficient measures the strength and direction of a relationship between two variables. the coefficient ranges from − to with indicating a strong positive relationship between two variables and − indicating a strong negative relationship. a correlation coefficient close to means the relationship between the two variables is very weak. died ( table ) . however, clinically, these differences are of doubtful significance, as the rr is at the discretion of the parent clinical team prior to referral to ecmo, and the lactate levels are normal in the survivors and only marginally elevated in those who died which will again be dependent on use of cvvh. the higher pao :fio (p:f) ratio was statistically significantly correlated ( p = . ) with a shorter duration of ecmo, which suggests those with less severe disease recover quicker ( table ) . many studies have reported on intensive care patient outcomes of the influenza a(h n )pdm pandemic, with or without the use of ecmo. in one study from australia, where ecmo was used, of patients with confirmed influenza a ( a(h n )pdm , un-subtyped) infection, ( %) had died mainly due to intracranial and other forms of haemorrhage ( n = ), or intractable respiratory failure ( n = ). another study from the usa, where influenza a(h n )pdm -infected patients had non-ecmo icu admission, of cases, ( %) developed acute respiratory distress syndrome (ards), of whom ( %) died. a more recent study from spain that reviewed influenza a(h n )pdm cases admitted to icu (non-ecmo) from - , found that of a total of cases, the mortality ranged from . % (for community-acquired influenza) to . % (for hospitalacquired influenza). these ecmo-icu case fatality rates of severe influenza a(h n )pdm infection are similar to ours of % reported here, though compared to the specific ecmo patient cohort, the causes of death in our patients were more variable, including intracranial and other haemorrhage ( n = ), sepsis and multi-organ failure ( n = ), respiratory failure ( n = ), post-cardiopulmonary resuscitation hypoxic brain injury ( n = ), and ischaemic bowel associated with atrial fibrillation ( n = ). thus, even after years of experience with this 'new' pandemic influenza a(h n )pdm virus, across almost the entire adult age-range ( ∼ - years in these previous studies), - it appears that for severe cases, globally, the survival of such patients appears not to have improved. this may be somewhat surprising as the world's populations have become more immunologically experienced with this virus, which is now considered as a seasonal influenza virus that should be conferring some degree of persisting, cross-reactive individual and herd immunity over consecutive seasons. this may be due to some predisposing genetic or environmental factors in individual patients, which should reinforce the general message that seasonal influenza immunisation is still recommended to minimise the number of people needing icu or ecmo support for severe influenza infection. more detailed monitoring on how these physiological parameters change over time (perhaps including more complex cytokine studies), in these severely ill, influenza a(h n )pdm -infected patients admitted to icu-ecmo units, may eventually yield data to improve their management and clinical outcomes. none. we read with interest the report by stalenhoef and colleagues in this journal who show that biomarker guided triage can reduce hospitalization rate in community acquired febrile urinary tract infection (ref). here we report on a prospective observational analysis of the biomarker: cd antigen like protein (cd l), in serum samples collected from patients diagnosed with pneumonia and healthy adults between and . the demographic and clinical characteristics of the adults (males . %; mean age ± years) with pneumonia were summarized in table . ( . %) bacterial pneumonia patients (including patients with confirmed bacterial pneumonia and patients with suspected bacterial pneumonia ) and ( . %) viral pneumonia patients were studied. there were significant differences in age, sex, wbc, neu%, crp, pct, cd l, apache ii scores and length of icu stay between bacterial pneumonia and viral pneumonia. the pathogens responsible for pneumonia were described in supplementary table . globally, gram-negative bacteria infection is more common than gram-positive bacteria infection in pneumonia. among them, acinetobacter baumannii ( , . %) was considered the major pathogen in gram-negative bacteria and staphylococcus aureus ( , . %) was considered the major pathogen in gram-positive bacteria. in viral pneumonia, influenza a (h n ) was detected as the unique pathogen. in the study of the diagnostic performance of serum cd l to identify etiology of pneumonia, as we found in supplementary fig. , no matter in total bacterial pneumonia, suspected bacterial pneumonia or confirmed bacterial pneumonia, the serum of cd l levels on day of pneumonia diagnosis were significantly higher than those in viral pneumonia and healthy control subjects. for evaluating the diagnostic performance of cd l to differentiate bacterial from viral infection in pneumonia, roc analysis was conducted for the above bacterial pneumonia (supplementary fig. ) and compared with routine laboratory markers ( table ). by horizontal comparison, we found that the best auc was for cd l (auc = . ), better than neu% (auc = . ), wbc (auc = . ), crp (auc = . ) and even pct (auc = . ). interestingly, by longitudinal comparison, the auc was observed highest in confirmed bacterial pneumonia (auc = . ), intermediate in all bacterial pneumonia (auc = . ), and lowest in suspected bacterial pneumonia (auc = . ), which may better elucidate the diagnostic performance of cd l for etiology diagnosis in pneumonia patients. although there are patients with suspected bacterial pneumonia for which no definitive pathogen was found, our result here may still provide a new treatment for bacterial infection identification in pneumonia patients for the current limitations in direct pathogen testing make it difficult to identify the pathogen at the time of diagnosis . besides, as a potential biomarker to distinguish pathogens - , cd l levels were also significantly correlated with wbc, neu%, crp and pct ( supplementary fig. ) in patients with pneumonia. in the study of the diagnostic performance of serum cd l to predict mortality in adults with pneumonia, mortality was defined as death occurring within days after the onset of pneumonia. as we observed in supplementary fig. a , serum cd l levels on day of pneumonia diagnosis were significantly higher in non-survivors ( n = ) than survivors ( n = ) ( p < . ). to ensure that serum cd l levels were not influenced by the class of the infection in the specimens, spearman's rank correlation analysis was performed between serum cd l levels and poor prognosis related scores , (sofa and apache ii scores) in patients with total bacterial pneumonia, suspected bacterial pneumonia, confirmed bacterial pneumonia and viral pneumonia, respectively. our correlation analysis between serum cd l levels and sofa or apache ii scores shows that no matter for bacterial pneumonia or viral pneumonia, the cd l levels showed positive correlation with sofa and apache ii scores ( supplementary figs. and ) . furthermore, the auc of cd l for identifying -day mortality in adult pneumonia patients was . ( supplementary fig. b) , a value means good diagnostic performance, which is consistent with gao's study before. therefore, we found that determining serum cd l concentrations on day of pneumonia diagnosis was of great value in identifying bacterial infection from viral infection and predicting day mortality in adult patients with pneumonia, which suggests that cd l may work for the etiologic diagnosis and could represent a novel biomarker for identification of a group of patients with pneumonia presenting with higher risk of death. these findings encourage further effort s aimed at exploring the clinical value of circulating cd l to help early clinical decision-making in human pneumonia. none. high morbidity and mortality (up to %). asf is a devastating threat to pig agriculture and is responsible for serious production and economic losses. the asfv genome is - kilo base pairs in length and has been divided into different genotypes based on their b l gene sequence, a gene which encodes the capsid protein p . , our previous study showed that the p gene located in a very low genetic diversity region of the genome. ye and colleagues, however, identified two novel genotypes xxv and xxvi, with genotype xxvi being especially divergent from all other genotypes. to examine this unexpected result, in this study, we reanalyzed their data to evaluate the reliability of these two genotypes. we collected available p gene sequences from ncbi ( http://www.ncbi.nlm.nih.gov/ ), which we then aligned with mafft software, a fast multiple sequence alignment program. the alignments show that genotype xxv (accession number fr ) has a single amino acid change at position compared to genotype i, while for genotype xxvi (accession numbers fr and fr ), the region coding for amino acid residues to differs greatly compared to all other genotypes ( fig. a) . to examine this in greater detail, we calculated genetic distance across the p coding sequence in bp sliding windows, with a step size of bp, between these two sequences and the other genotypes ( fig. b) . this sliding window analysis shows these two sequences for genotype xxvi have a region that is very divergent, with genetic distance up to . from the other genotypes, while the genetic distances of the remaining regions are less than . ( fig. b) . genetic distances for asfvs were calculated for coding gene sequences, from available complete genomes of asfvs, to assess the overall divergence. pairwise genetic distances of each gene for all asfv strains were calculated. the mean pairwise genetic distance for asfv genes was . ( fig. ) , which is much lower than this divergent region of these two sequences for genotype xxvi ( . ). therefore, it seems highly unlikely that a gene has such a highly divergent region. since recombination frequently occurs in asfvs, we conducted a recombination analysis with the rdp program, which used the seq, bootscan, chimaera, genecov, lard, maxchi, rdp and siscan detection methods, to determine whether recombination might have occurred in the xxvi genotype. we found reliable evidence for recombination events in both p genotype xxvi sequences ( fig. c) . this suggests that the very highly divergent region of this p genotype is not homologous with other p genotypes. we used blastn, from ncbi ( https://blast.ncbi.nlm.nih.gov/blast.cgi ), to identify a source for this highly divergent region, however, no similarity sequence was found. we then mapped the multiple amino acid changes found in genotype xxvi to the d structure of p ( fig. ) . the changed sites (marked in red in fig. ) are located in the dec loop, a region which plays an important role in the formation of the trimer spike. the amino acid mutations result in changes of electrostatic potential, hydrophobicity, and steric hindrance. it seems unlikely to have so many changes in such a functionally important region. in our previous studies we noticed that sequences directly submitted by individual laboratories to genbank often contain errors such as misidentification of species, sampling error, contamination, or are pseudogenes, which can lead to sequence analysis problems and erroneous conclusions. , sequences that deviate from the overall intraspecific pairwise divergence are potentially erroneous. , since genotype xxvi deviates from other genotypes not only in genetic distance, but also in protein structure, and mutations occur in the flanking regions of the sequences, we deduced that these reported mutations might be due to low quality sequencing. we identified the original manuscript reporting the three sequences of genotypes xxv and xxvi, where the authors stated that the "alignment and translation of sequences obtained from sardinian isolates revealed that the c-terminal end of p gene was completely conserved between the sequences compared". this statement indicates that these sequences did not considerably diverge from previously reported asfv p sequences, and thus, suggests that an error in these sequences had been introduced upon submitting them to genbank. further examination of the original samples and sequences is needed. we contacted the corresponding author of this manuscript to check these three sequences, and were told that these three p sequences were all genotype i, and had some errors when submitted to genbank. in conclusion, the two novel genotypes of asfvs (xxv and xxvi) identified by ye and colleagues are misled by problematic sequences. as reminded by our previous studies, many problematic sequences are present in genbank, which can lead to problems in downstream analyses. , thus, when published data is used for new analyses, the first set in the process of data analyses should be to filter these sequences for potential errors to reduce the possibility of reaching incorrect conclusions. if conclusions are based on obviously strange sequences, then we should trace back the data to their original source, and manuscript, and contact the corresponding authors before making conclusions based on these sequences. the authors declare no conflict of interest. fig. . the analyses of phylogenetic tree, recombinant, and nucleotide divergence between xi and the other known subtypes ( a- xh) based on full-length hbv genome sequences. (a) the known hcv subtype reference sequences ( a- xh) from the previous report were used. phylogenetic analysis was performed by the maximum-likelihood method, based on the gtr + g + i substitution model, with bootstrap replicates using the software mega v . the sequences of hcv xi (ynkh and ynkh ) are marked in red dot. (b) bootscan plots were constructed using simplot . . software based on replicates with a -bp sliding window moving in steps of bases. (c) pairwise comparisons of nucleotides similarities between hcv xi strains and reference genotype sequences. , deaths per year. currently, daa treatment regimens that target ns /ns a protease, ns a phosphor-protein and the ns b polymerase have shown high safe and high rates of sustained virologic response in hcv chronically infected patients ( > %). however, under selective pressure from these drugs, drug resistance-associated substitutions (ras) can emerge during this therapy and result in treatment failure in − % of patients. therefore, hcv infection is still a major global health concern. to date, eight confirmed genotypes have been characterized based on > % sequence divergence in the complete hcv genome, and genotypes are further classified into > subtypes with a sequence divergence of > % to other subtypes of the same geno-type. in the current study, we characterized a new hcv subtypes among chronic hepatitis c patients in yunnan, china, initially designated as xi, further analyzed its evolutionary history and investigated its baseline ras by next generation sequencing (ngs) method. plasma samples were collected between january and october from chronic hepatitis c patients from kunming city in yunnan, china (fig. s a) . the samples met the following inclusion criteria: ( ) hepatitis c antibody-positive for months with normal serum alanine aminotransferase (alt) levels; ( ) subject was residing in yunnan province and was over years old; ( ) complete demographic information and clinical data were available; ( ) consented to the use of patient information in studies on hcv epidemics; and ( ) were treatment-naïve during sampling. there was no epidemiologic link among these individuals. the study was approved by the first people's hospital of yunnan province ethics committee. written informed consent was obtained from all participants prior to the study. out of a total of chronic hepatitis c patients, partial ns b gene fragments were successfully amplified and sequenced with a success rate of . % ( / ). multiple subtypes were identified in subjects, including subtype b ( . %, / ), a ( . %, / ), b ( . %, / ), a ( . %, / ), n ( . %, / ), a ( . %, / ), and a ( . %, / ) (fig. s b) . interestingly, the remaining two strains ( . %, / ) involving ynkh and ynkh together with the isolate km reported formed a novel separate cluster in the genotype with an % bootstrap value, indicating a potential new hcv subtype . to confirm that the two strains belong to a novel hcv subtype , their complete genome sequences were successfully amplified and sequenced with overlapping fragments. further, phylogenetic analysis was performed along with hcv reference sequences of representative subtypes a- xh. the result showed that the two strains and isolate km formed a distinct monophyletic cluster supported by a high bootstrap value of %. the three strains were isolated from three hiv- infected patients without obvious epidemiological linkage in yunnan and showed no evidence of recombination using bootscan analysis ( fig. (b) ). moreover, the intergroup nucleotide divergence (mean ± sd) % over the fulllength genome sequences of the isolates (ynkh , ynkh , and km ) were compared to that of representative subtypes ( a- xh) ( fig. (c) ). the results revealed that the three strains were different from known hcv subtypes of a- xh by . - . %. therefore, the three strains are initially designated xi. to better understand the time of emergence of hcv xi, we performed bayesian molecular clock analyses using full-length genome sequences to estimate the time to the most recent common ancestor (tmrca). as shown in fig. (a) , the estimated tmr-cas for the genotype xi was . [ % highest probability density (hpd): . , . ]. in addition, to further investigate baseline ras of subtype xi, naturally occurring resistance-associated substitutions (ras) were analyzed for the ns , ns a and ns b sequences using next generation sequencing (ngs) method. strikingly, hcv xi strains contain the substitution v with a % frequency of mutations in the ns a protein contributing to resistance to velpatasvir of ns a phosphoprotein inhibitor, suggesting that the subtype xi maybe basically resistant to ns a inhibitors ( fig. (b) ). among the hcv eight genotypes, genotype exhibits a high degree of genetic complexity and diversity, and subtypes have been confirmed by the international committee on taxonomy of viruses. in china, hcv genotype is common, and subtype a is the most prevalent subtype, primarily distributed in guangdong, n is the second most prevalent subtype, mainly found in yunnan, followed by subtypes xa, g, v, w, e, b, j, q,and r among genotype isolates. - to our knowledge, xi is the eighth detection of novel hcv subtypes in china combined with previously identified a, e, n, v, xa, xe and xh, resulting in genotype to expand to subtypes in the world. our findings again demonstrated that hcv genotype was more complex and diverse. in summary, we characterized a new hcv subtype xi based on the characteristics of a monophyletic cluster, > % genetic distances, no significant evidence of recombination, and no epidemiologic link among individuals. in addition, bayesian analyses showed that xi may originate around the year , and the strains of hcv xi naturally contain the substitution v in the ns a protein contributing to resistance to velpatasvir of ns a phosphoprotein inhibitor. the present finding again highlights the genetic characteristics and hcv strains in yunnan, and the urgent need for continuous molecular screening and epidemic surveillance in yunnan to implement effective measures to reduce hcv transmission. the authors declare no competing financial interests. we recently read the article by corma-gómez a. et al. on which the authors described a higher probability of relapses with sofosbuvir/ledipasvir weeks compared with weeks of hcv (hepatitis c virus) among hiv (human immunodeficiency virus)/hcv coinfected patients. in this regard, coinfections of hiv/ hcv also with hepatitis b virus (hbv) is associated with high mortality and comorbidity too. the persistence of hbv dna within the core cell in the absence of hbsag and even after clearance of the infection has been described previously in immunosuppressed patients, where hbv screening and prophylaxis is recommended. interestingly, hbv reactivation has recently emerged during or after hcv treatment with direct-acting antivirals (daa). [ ] [ ] [ ] the us food and drug administration issued a warning about this risk in , until that moment cases were reported, two of which died. although specific mechanisms of this event are not well known, it has been suggested that hcv core proteins could inhibit hbv replication and hbsag production as well as production of envelope proteins, being hbcab the only marker of the presence of hbv. in this context, treatment with daa would produce a drastic and rapidly blocking of hcv replication providing the opportunity to hbv to emerge and produce an immune reconstitution syndrome. the interference hbv-hcv has been outlined in % of patients with chronic hbv infection (hbsag-positive serology) and . % of patients with resolved hbv infections (hbsag-negative and hbcabpositive) in a recently published systematic review and metaanalysis of patients with hcv-hbv. in most cases, these reports have focused on coinfection hcv-hbv, but there is still a concern about patients triple-infected with hcv, hbv and hiv. although most cases reported occur in hbsag-positive, the main concern affects to patients with a basal serology showing hbcab-positive, hbsag-negative and hbsab-negative. hbsagpositive was associated with higher rates of hbv reactivations compared with hbsag-negative and hbcab-positive patients. there is no clear information about this issue in hbsag-negative, hbcab-positive, and, when occurs, it is considered an uncommon event. reactivation of hbv is characterized by reappearance or increase in hbv dna levels, and could also be accompanied by symptoms of hepatitis. the cases reported previously did show difference in the time of presentation of clinical symptoms, they used to start either during or after daa treatment. it seems that hbv reactivation usually occurs early after daa initiation treatment ( - weeks) while otherwise can occur after treatment completion. in that way, it seems necessary that hbv infection should be monitored early after daa initiation. the most recent european association for the study of the liver (easl) guideline about hbv infection, recommends that patients hbsag-negative and hbcab-positive undergoing daa treatment should be monitored and tested for hbv reactivation only in case of alt elevation. they also recommend performing hbv dna levels only in case of alt increase. at the same time, the american association for the study of liver diseases (aasld) and the infectious disease society of america (idsa) guideline has been recently updated recommendations to monitor hbv dna levels only in patients hbsag-positive, but they emphasize that there is not enough data to monitoring dna among patients hbcabpositive or hbcab-positive and hbsab-positive. they remark that a reactivation should be considered if an unexplained increase in liver enzyme is present. in hiv patients, they provide the same recommendations. in a recent review of the literature, the authors also recommend to perform an hbv dna only in patients with altered alt. a meta-analysis recommended not to perform an hbv dna test in this case due to low rate of incidence and the associated cost which needs to be considered especially in an endemic hbv areas. few data exist in hiv patients. the fact that many triple-infected patients are receiving antiretroviral therapy including (art) nucleoside/nucleotide analogous, as tenofovir disoproxil fumarate (tdf) or tenofovir alafenamide (taf), both active against hbv, suggest that hbv reactivation rate could be underestimated. in a recently published review, chang et al., recommend to perform an hbv dna test at baseline in triple-infected patients. if positive, an hbv-active antiretroviral therapy (art) should be started and hbv dna needs to be monitored every weeks during treatment and until week after completion of treatment. however, if baseline hbv dna is negative they match with aasld/idsa and easl recommendations. one of our patients has a basal serology with hbcab-iggpositive, both hbsag-and hbsab-negatives, and undetectable hbv dna levels, prior to treatment with daas. regarding hiv infection, he has an analogues-free regimen. one month after having finished treatment with daas, the patient consulted because of abdominal pain, nausea and jaundice. he had a total bilirubin level of mg/dl, ast iu/l, alt iu/l and inr . . a hbv viral load of , , iu/ml was detected; hbsag, hbcab-igm and hbeag were positive. there were no reasons to believe that he was re-infected. treatment with entecavir was initiated; however, the clinical evolution was unfavorable and died as a result of an acute liver failure. the hbv viral load was requested from the stored samples drawn during the treatment of hcv showing that hbv viral load was undetectable at the beginning of treatment and in week , but progressively increased to iu/ml in week and up to , iu/ml in week after treatment completion. during the follow-up of daa treatment alt and ast remained normal. this case changed our daily practice, since then all hiv patients and more specifically those not treated with either tdf or taf and presenting a previous hbcab-positive, are followed using dna levels and not only monitoring hepatic enzymes, as recommended by guidelines. we consider that this case may reflect the necessity of change the current guidelines. we recommend to perform a periodic monitoring of hbv reactivation using hbv dna during and after daa therapy in hbsag-negative and hbcab-positive patients, independently of hbsab presence, hepatic enzymes and clinical symptoms, particularly in hiv patients who are not receiving active treatment of hbv. the study was not funded. authors declare that there is no conflict of interest. recently, a notable pattern of synchrony of influenza a and b virus, and respiratory syncytial virus incidence peaks globally was reported in this journal. a previous study characterized seasonal pattern of influenza a and b in china and identified three epidemiological regions featured by distinct seasonality. on the basis of laboratory surveillance data from chinese provinces spanning about years from october through january , our study further characterized seasonal patterns of circulating influenza a subtypes and influenza b lineages in the three defined epidemiological regions. our study revealed that pre- a(h n ) and a(h n ) displayed wintertime and summertime epidemics in midlatitude and southernmost chinese provinces with subtropical climate, wavelet analysis demonstrated the two subtypes displayed twice-annual cycle in some years in mid-latitude chinese provinces ( fig. (a)-(h) ). however, the two subtypes peaks in the winter with annual or longer cycle in northern chinese provinces. influenza a(h n )pdm b/victoria and b/yamagata virus all displayed epidemics in the winter or winter-spring with annual or longer cycle in all three epidemiological regions. we developed univariate and multivariate regression models to evaluate the association between climatic factors and the presence or absence of epidemics of each influenza subtype and lineage (positive proportion ≥ %) in the southernmost provinces where heating system is not generally used in the winter so temperature and relative humidity in external conditions in winter are close to those in indoor environment where people spend most of the time. we fitted the mixed-effects logistic regression model to control for the repeated measurements in each province of the region cluster. we kept one of temperature and absolute humidity (representative of vapor pressure) with smaller akaike information criterion in the model to reduce of multi-collinearity due to a high degree of correlation between the two factors. our analysis indicated temperature, humidity and rainfall were environmental predictors of influenza subtype/lineage-specific epidemics in the southernmost provinces when a -week lag of influenza epidemics behind climate was considered, which was similar to the findings from some ecological studies ( table ). our study indicated the u-shaped relationship between absolute humidity (ah) and pre- a(h n ) or a(h n ) epidemics in the southernmost provinces, and suggest that high levels of ah in the summer, and low levels of ah in the winter increased the possibility of epidemics of the two subtypes. in our analysis, lower temperature was an environmental driver of a (h n )pdm and b/yamagata epidemics in the southernmost provinces while there were bimodal associations between temperature, rainfall and b/victoria epidemics with highest probability of b/victoria epidemics at . °c of daily average temperature and . mm of daily average rainfall. although seasonal changes in human behaviors, such as school attendance or crowding indoors, and seasonal variations in immunity, such as melatonin and vitamin d levels have been proposed to account for the seasonal nature of influenza, our findings suggest that the heterogeneity in influenza subtype/lineage-specific seasonality patterns could be driven by seasonal variations in virus survival, transmission and adaptive immunity by influenza subtype and lineage because of the same behavior modes and background of non-adaptive immunity in the same regions and seasons. we propose a hypothesis: under humid and hot condition the dominant transmission mode(s) for a(h n )pdm , b/victoria and b/yamagata might have reduced efficiency, however, there could be effective transmission mode(s) for a(h n ) and pre- a(h n ) virus. some experimental studies were performed to establishing a causal link between humidity, temperature and influenza virus survival/transmission. transmission of influenza a (h n ), a(h n )pdm , b/victoria and b/yamagata virus by respiratory droplets or aerosols in the guinea pig model proceeds most readily under cold, dry conditions. low humidity and temperature increased the stability of influenza virus in aerosols and on surfaces. furthermore, aerosol transmission of a (h n ) virus in the guinea pig model was almost completely blocked at °c, but contact transmission of a (h n ) virus seemed to be efficient at different level of humidity and °c. it remains unclear if high temperature and humidity levels have effect on aerosol and contact transmission of pre- a(h n ), a(h n )pdm , b/victoria and b/yamagata virus among hosts and their stability on surfaces. of note, an experimental study found the survival durations of a(h n ) strains on swiss banknotes were significantly longer than pre- a(h n ) and b/victoria virus. further studies are needed to understand how efficient are these transmission modes for different influenza subtypes or lineages, which is/are dominant mode(s) of transmission among hosts, and which of potential mechanisms is at play under humid and hot condition. one of our findings was the mutual inverse association between a(h n ) and a(h n )pdm epidemics, which provided the evidence on interference between the two influenza a subtypes perhaps possibly due to multiple immune mechanisms. however, our study showed b/yamagata epidemics were positively correlated with a(h n ) epidemics, suggesting b/yamagata epidemics across over study years that were weak could get well along with simultaneous weak h n epidemics. understanding of influenza seasonality is important to define optimal timing of influenza vaccination campaigns. our study indicated that a(h n ) virus brought about twice-annual epidemics in some years in mid-latitude chinese provinces and more frequent summertime epidemics in southernmost chinese provinces, which questions if a single annual influenza vaccination campaign starting in october can offer optimal protection against summertime epidemics of a (h n ) virus in mid-latitude and southernmost chinese provinces. in recent years, it has been reported that mismatches of a(h n ) virus between the influenza vaccine strains and circulating strains were identified frequently, and vaccine effectiveness of a(h n ) virus declined within - months postvaccination. in conclusion, we identified the heterogeneity of seasonality pattern of pre- a(h n ) or a(h n ) virus in three epidemiological regions of china, and different environment predictors for influenza subtypes and lineages in the southernmost provinces. further work should focus on understanding difference in virus survival, transmission by influenza subtype and lineage under humid and hot conditions. bjc has received research funding from medimmune inc. and sanofi pasteur, and consults for crucell nv. the authors report no other potential competing interests. as this study included data from the national influenza surveillance system, ethics approval was not required. not applicable. the datasets at national level analyzed during the current study are available in the world health organization flunet. the datasets with more specific information analyzed during the current study are available in chinese national influenza surveillance informatio system, but they are not open-access datasets. these influenza surveillance data can be available from chinese national influenza center on reasonable request. this study was supported by the national mega-projects for infectious diseases (grant number zx - - ), national natural science foundation of china (grant number ) and emergency prevention and control project of ministry of science and technology (grant number ). the funding bodies had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish. reported in zhejiang in . in this study, we identified ten cases of imported chikv infection in travelers returning to yunnan from southeastern asia in . out of the ten patients with imported chikv infection examined in this study, nine patients had traveled back from myanmar and one patient had travelled back from thailand ( fig. (a) ). all the patients displayed different degrees of symptoms, such as fever, cough, muscle pain, and rash. the details of all the symptoms are shown in table . chikv infection was diagnosed using specific real-time reverse transcription-pcr. serum specimens were collected from the ten patients that tested positive for chikv by real-time pcr analysis, in yunnan between may , and august , . the current study was approved by the medical ethics committee of kunming university of science and technology. written informed consent was obtained from all the participants. a new coronavirus associated with human respiratory disease in china early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia angiotensinconverting enzyme is a functional receptor for the sars coronavirus a pneumonia outbreak associated with a new coronavirus of probable bat origin emergence of sars-like coronavirus poses new challenge in china bat origin of a new human coronavirus: there and back 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chikungunya virus chikungunya virus emergence is constrained in asia by lineage-specific adaptive landscapes this work was supported by henan emergency project for prevention and control of novel coronavirus, the earmarked fund for modern agro-industry technology research system of china (cars- ) and the special fund for henan agriculture research system (s - ). the funders had no role in study de-sign, data collection and interpretation, or the decision to submit the work for publication. we thank jing li and hao-nan wang for the helpful discusses and suggestions. this work is supported by the open research fund of key laboratory of digital earth science ( lde ), and by the fundamental research funds for the central universities under grant no. qd . this work was supported by the national natural science foundation of china ( ) and the guangdong provincial natural science foundation ( a ). we thank le kim thanh, le nguyen truc nhu, and lam anh nguyet for their logistic support. we are indebted to patients for their participations in this study.this study was funded by the wellcome trust of great britain ( /b/ /z and /z/ /z ). supplementary material associated with this article can be found, in the online version, at doi: . /j.jinf. . . . we would like to thank the patients and healthy volunteers in the first affiliated hospital of chongqing medical university for their cooperation and support. this work has been financially supported by national natural science foundation of china (no. and no. ). we thank chinese national influenza surveillance network for contribution in influenza epidemiological and laboratory surveillance. we thank the members of the yunnan international travel healthcare center and kunming changshui airport customs for the data and sample collection. supplementary material associated with this article can be found, in the online version, at doi: . /j.jinf. . . . supplementary material associated with this article can be found, in the online version, at doi: . /j.jinf. . . . recent correspondence in this journal has highlighted the current threat posed by recently-emerging imported chikungunya virus (chikv) in febrile returning travellers. chikungunya fever is infection caused by the chikv and is characterized by fever, arthralgia, myalgia, headache, and rash. chikv belongs to the genus alphavirus within the togaviridae family and is transmitted to humans by the bite of infected mosquitoes-ae. aegypti and ae. albopictus . since the first report of chikv infection in humans in tanzania, intermittent outbreaks have been documented in africa, south america, southern and southeastern asia, and the indian ocean islands; thus, its outbreak has become a global public health problem. to date, three evolutionary distinct chikv genotypes, namely west african (wa), east/central/south african (ecsa), and asian have been identified, based on phylogenetic analyses. a novel lineage of chikv-the indian ocean lineage (iol)-has also been reported, which descended from the ecsa genotype during an outbreak on the island of la reunion between and . recently, it has been reported that iol of chikv has spread to malaysia, singapore, thailand, and indonesia. in china, the first case of imported chikv infection was found in yunnan in . subsequently, several sporadic cases of nonindigenous chikv infection have been described. in , the first outbreak of chikv fever with cases was documented in guangdong. recently, another outbreak of chikungunya fever was table epidemiological information on ten febrile returning travelers infected with chikv in this study. in this study, nine complete genome sequences isolated from serum samples were successfully amplified and sequenced with overlapping fragments, and then the sequence obtained was deposited in genbank under accession no. mn -mn . compared with the nucleotide sequences of the available from the ncbi database, the nine strains shared the highest . - . % nucleotide identity with the east/central/south african lineage strain thail reported previously in thailand, . further, bayesian maximum-clade-credibility tree for full-length nucleotide sequences were constructed using the beast package v. . . . phylogenetic analyses revealed that the ten chikv strains clustered into the homogeneous indian ocean clade of the ecsa genotype ( fig. (b) ).notably, the ten chikv strains isolated from serum samples possessed the mutation k e in the e gene and v a in the e gene; these mutations are associated with significant increase in viral infectivity in ae. aegypti . the strains also possessed g d and i t substitutions in the e gene; these mutations contribute to increased chikv fitness in ae. albopictus. however, the a v mutation in the e gene that is related to significant increase in viral infectivity in ae. albopictus was not observed in any of the strains. in summary, we characterized ten cases of human infection caused by imported ecsa genotype chikv in yunnan, china and successfully isolated nine infectious chikvs from the chikvpositive serum samples. the mutations associated with significant increase in viral infectivity for ae. aegypti or ae. albopictus were also observed in these strains. geographically, the yunnan province is in southeastern china and shares its border with southeast asian countries (laos, vietnam, and myanmar) that are most affected by chikv. with the increase of tourism and trade with southeast asian countries, cases of imported chikv infection are constantly increasing and may have the potential for re-emergence and autochthonous transmission to yunnan. the present study highlights the urgent need for continuous molecular screening and epidemic surveillance for chikv and its vectors to prevent future outbreaks of chikv infection among the human population of yunnan. this work was supported by the national natural science foundation of china (nsfc) ( u ), the reserve talents project for young and middle-aged academic and technical leaders of yunnan province ( hb ), and youth talent program of yunnan "ten-thousand talents program" (ynwr-qnbj- - ). the authors declare no competing financial interests. key: cord- -l hkn li authors: luyt, charles-edouard; bouadma, lila; morris, andrew conway; dhanani, jayesh a.; kollef, marin; lipman, jeffrey; martin-loeches, ignacio; nseir, saad; ranzani, otavio t.; roquilly, antoine; schmidt, matthieu; torres, antoni; timsit, jean-françois title: pulmonary infections complicating ards date: - - journal: intensive care med doi: . /s - - -z sha: doc_id: cord_uid: l hkn li pulmonary infection is one of the main complications occurring in patients suffering from acute respiratory distress syndrome (ards). besides traditional risk factors, dysregulation of lung immune defenses and microbiota may play an important role in ards patients. prone positioning does not seem to be associated with a higher risk of pulmonary infection. although bacteria associated with ventilator-associated pneumonia (vap) in ards patients are similar to those in patients without ards, atypical pathogens (aspergillus, herpes simplex virus and cytomegalovirus) may also be responsible for infection in ards patients. diagnosing pulmonary infection in ards patients is challenging, and requires a combination of clinical, biological and microbiological criteria. the role of modern tools (e.g., molecular methods, metagenomic sequencing, etc.) remains to be evaluated in this setting. one of the challenges of antimicrobial treatment is antibiotics diffusion into the lungs. although targeted delivery of antibiotics using nebulization may be interesting, their place in ards patients remains to be explored. the use of extracorporeal membrane oxygenation in the most severe patients is associated with a high rate of infection and raises several challenges, diagnostic issues and pharmacokinetics/pharmacodynamics changes being at the top. prevention of pulmonary infection is a key issue in ards patients, but there is no specific measure for these high-risk patients. reinforcing preventive measures using bundles seems to be the best option. acute respiratory distress syndrome (ards) regroups a wide range of diseases whose consequence is lung inflammation, alveolar damage and pulmonary edema [ ] . whatever the initial lung injury, patients with ards are prone to develop secondary pulmonary infection, namely ventilator-associated pneumonia (vap). recent data from the center for disease control and prevention suggest that vap rates are not dropping in the usa despite patients with ards exemplify the apparently paradoxical immune state of critically ill patients, whereby activated immune cells mediate organ damage while manifesting impaired antimicrobial defenses [ ] . impaired cellular functions have been identified across both the innate and adaptive arms of the immune system [ , ] , and appear to be stereotyped rather than specific to any precipitating cause of ards [ ] . this apparently paradoxical state is due to the ability of pro-inflammatory and tissue damage molecules to drive immune dysfunction [ , ] . dysfunctional immune cells are found in the lung as well as peripheral blood [ ] . interestingly, lung mucosal immune defects are protracted after the cure from primary inflammation, thus increasing the susceptibility to hospital-acquired pneumonia and ards for weeks after systemic inflammation [ ] . following experimental pneumonia, pulmonary macrophages and dendritic cells demonstrated prolonged suppression of immune functions which increased the susceptibility to secondary infection [ ] . expansion of immuno-modulatory regulatory t cells (t reg ) is also seen and may mediate impaired innate as well as adaptive immune function [ ] . patients with suspected vap, including those with ards, demonstrated impaired phagocytic function of alveolar neutrophils, which interestingly appeared to be mediated by different mediators than those driving dysfunction in the peripheral blood [ ] . while we have a growing understanding of the mediators driving dysfunction, and the intracellular mechanisms which drive them [ ] , we do not as yet have proven therapies although there are multiple potential agents [ ] . when aiming at modulating immunity during inflammation, it is important to differentiate innate and adaptive immune cells responses. while exhaustion and apoptosis seem to be central to lymphocyte defects observed in critically ill patients [ ] , some innate immune cells undergo reprogramming involving epigenetic reprogramming and increased cellular metabolism, a phenomenon so-called trained immunity, resulting in high production of inflammatory cytokines such as il- and tnfα during secondary immune challenge [ ] . while glucocorticoids are classically considered as immunosuppressive drugs, it has been shown that they can prevent the immune reprogramming observed after inflammatory response [ ] , thus limiting the susceptibility of patients admitted to the intensive care unit (icu) to respiratory complications such as pneumonia or ards and improving outcomes of patients with ards [ ] . part of the complexity of pulmonary super-infections arises from the interaction between the injured host with their pulmonary microbiome. although considerably less abundant and diverse than the better studied gastrointestinal microbiome [ ] , the pulmonary microbiome is increasingly well defined and undergoes significant changes during critical illness and ards [ ] . the major role of respiratory microbiota on mucosal immunity and respiratory functions in health suggests that its alterations could be involved in the respiratory complications observed in critically ill patients [ ] . indeed, mechanically ventilated patients experience a reduction in diversity of pulmonary microbes and an increase in enteric-type organisms, even in the absence of overt infection [ ] . early alterations of the lung microbiome, notably increased bacterial burden and biofilm formation, enrichment with gut-associated bacteria and loss of diversity, are associated with the risk of ards and the duration of mv support in critically ill patients [ ] . pre-existing dysbiosis, such as that induced by tobacco smoke, may also influence the development of ards following major trauma [ ] . alongside changes in bacterial species, it is common to find reactivation of latent herpesviridae such as herpes simplex virus (hsv) and cytomegalovirus (cmv) [ ] . the drivers of these changes are incompletely understood but are multi-factorial, with possible mechanisms illustrated in fig. [ , , ] . adding further complexity is the potential for microbes themselves to drive further immune dysfunction [ ] . vap should therefore be conceptualized as less a de novo infection by an exogenous pathogen, but rather a dysbiotic response to critical illness with overgrowth of specific genera of bacteria [ ] . appropriate antibiotic therapy targeting the dominant species, those frequently detected by culture, is key in certain patients but risks exacerbating dysbiosis and further harm to the patient [ ] . what remains to be proven is whether interventions to restore symbiosis, i.e., to increase bacterial diversity rather than only eliminating dominant species, can improve outcomes [ ] . although the experience of fecal transplantation in clostridium difficile associated diarrhea suggests that microbial transplantation may be an effective form of therapy [ ] , negative experience of probiotics in pancreatitis and recent examples of 'probiotic' bacteria causing infections sound a note of caution [ , ] . developing effective therapies for respiratory dysbiosis will require tools to profile the host peripheral pulmonary superinfections in ards patients considerably impact patients' prognosis which is favored by altered local and systemic immune defenses. the poor outcome of ards with pulmonary superinfections is probably related to the lack of early accurate diagnostic methods and difficulties in optimizing therapy. and pulmonary immune cell function and the pulmonary microbiome [ ] . hyperoxia is common in patients receiving mv for ards. a secondary analysis of the lung safe trial [ ] reported that % of the analyzed patients had hyperoxia on day , and % had sustained hyperoxia. while two randomized controlled trials found beneficial effect of avoiding hyperoxia [ , ] , a recent large international multicenter trial demonstrated no effect of conservative oxygen therapy in a cohort of critically ill patients [ ] . however, a subsequent sub-study raised the possibility of clinically important harm with conservative oxygen therapy in patients with sepsis [ ] . oxygen toxicity is mainly related to the formation of reactive oxygen species (ros), especially during hypoxia/ re-oxygenation and long exposure to oxygen. high level of inspired oxygen is responsible for denitrogenation phenomena and inhibition of surfactant production promoting expiratory collapse and atelectasis [ ] . absorption atelectasis occurs within few minutes after pure o breathing. in mechanically ventilated patients, atelectasis seriously impairs cough reflex and mucus clearance resulting in abundant secretions in the lower airways and higher risk for vap. prolonged hyperoxia also impairs the efficacy of alveolar macrophages to migrate, phagocyte and kill bacteria, resulting in decreased bacterial clearance [ ] . hyperoxemia markedly increased the lethality of pseudomonas aeruginosa in a mouse model of pneumonia [ ] . additionally, o can cause pulmonaryspecific toxic effect called hyperemic acute lung injury (hali) (fig. ) . although earlier studies reported a link between high fio and atelectasis, further studies are required to evaluate links between hyperoxia and mortality or vap. in a single center cohort study of patients, among whom ( %) had vap, multivariate analysis identified number of days spent with hyperoxemia [or = . , % ci: ( . - . ) per day, p = . ], as an independent risk factor for vap. however, the study was retrospective, performed in a single center, and the definition used for hyperoxia (at least one pao value > mmhg per day) could be debated [ ] . in the recent hypers s randomized controlled trial [ ] , the percentage of patients with atelectasis doubled in patients with hyperoxia compared with those with normoxia ( % vs. %, p = . ). however, no significant difference was found in vap rate between hyperoxia and control group ( % vs. %, p = . ). however, vap was not the primary outcome of this trial, and there is no clear definition of icu-acquired pneumonia. further well-designed studies are required to determine the relationship between hyperoxia and vap. prone position is recommended in patients with severe ards and is commonly used in this population. there is a rationale supporting a beneficial effect of prone position on the incidence of vap, as it facilitates secretion drainage and allows atelectasis resolution. previous human and animal studies have clearly showed a link between atelectasis and vap, and reported that efficient secretion drainage might result in lower incidence of vap [ ] . on the other hand, prone position might facilitate microorganisms' dissemination and increase microaspiration of contaminated secretions. the results of studies on the relationship between prone position and vap should be interpreted with caution, because of some limitations such as observational design, small number of included patients and confounding factors. five recent studies were performed in patients with protective lung mv, including four randomized controlled studies and one large observational cohort. mounier et al. [ ] reported no significant reduction of vap incidence in a large cohort (n = ) of hypoxemic patients positioned in the prone position, as compared to those who did not receive this intervention [hr . ( % ci . - . )]. one randomized controlled trial reported reduced risk for vap in multiple trauma patients who were subjected to intermittent prone position, as compared to those who did not (p = . ) [ ] . however, the incidence of vap was very high in the control group ( %), and the number of included patients was small (n = ). three other randomized controlled trials reported no significant relationship between prone position and vap [ , , ] . however, these studies lack information on efficient preventive measures of vap, such as the use of subglottic secretion drainage or continuous control of tracheal cuff pressure, and vap was not their primary outcome. in summary, available data do not support a significant relationship between prone position and vap, although it has demonstrated beneficial effects on mortality in severe ards. the diagnosis of lung infections in patients with ards is challenging [ ] . the diagnosis of pneumonia, the dominant respiratory infection of concern in ards, is ultimately a histopathological diagnosis which requires the presence of airspace inflammation and an infecting organism. however, obtaining lung tissue for diagnosis is seldom practical or desirable in ventilated patients [ ] . the clinical features of systemic inflammation and localizing chest signs such as crepitations and bronchial breathing are non-specific and insensitive. while radiological evidence of airspace infiltration is useful, the gold standard of computed tomography is not practical for most patients, leading practitioners to rely on plain radiographs and ultrasound, and even computed tomography cannot always reliably distinguish between infective and non-infective causes of airspace infiltration [ , ] . use of clinical and radiographic criteria alone are likely to significantly overestimate the rate of pneumonia and lead to excessive, potentially harmful, use of antibiotics [ ] . it is also important to recall that pneumonia itself is the commonest precipitant of ards, which, together with the bilateral radiographic alterations in ards patients, creates an additional challenge for the ascertainment of a "new or worsening pulmonary infiltrate", a condition required for clinical diagnosis of vap [ ] . another challenge is the distinction between ventilator-associated tracheobronchitis (vat) and vap. vat is defined as a lower respiratory tract infection without involvement of the lung parenchyma (and therefore without new/progressive chest x-ray infiltrate). the distinction between vat and vap in ards patients remained challenging given the poor accuracy of chest radiograph to detect new infiltrates. obtaining samples from the lungs for microbiological culture is crucial to the establishment of infection. however, there is considerable variability in the timing and type of specimen obtained in practice [ ] . the identification of infection can be complicated by colonization of the proximal airways, which happens rapidly after intubation and is frequent in ards patients [ ] . it is important to differentiate between colonization (presence of bacteria, even at a high burden, in the respiratory tract without lung infection), a harmless phenomenon, and infection. although protected deep lung sampling by broncho-alveolar lavage or protected specimen brush reduces the risk of false positives relative to endotracheal aspirate, this has not been convincingly demonstrated to alter outcomes although observational data suggest they can safely reduce antibiotic use [ ] . although falsepositive results from proximal colonization are a significant problem, intercurrent use of antibiotics is common in ards patients and increases the risk of false-negative culture. this is, increasingly, being addressed by the use of culture-independent molecular technique; however, the utility of the tools available is limited by their restricted range of organisms covered and the risk of over-sensitive detection of irrelevant organisms driving inappropriate use of antimicrobials [ ] [ ] [ ] . physicians should be aware of this particular point and therefore interpret with caution the results of these tests. there are very few prospective studies demonstrating the impact of molecular diagnostics on patient management and the results of forthcoming trials are awaited. antigen detection in the lower respiratory tract can also aid diagnosis, especially with organisms such as aspergillus where culture and pcr are imperfect [ ] . the value of aspergillus sp. and aspergillus fumigatus pcr is promising, but remain to be evaluated in ards patients. in patients with ards and bilateral radiographic infiltrates, there remains a question of which region to sample invasively. while trials have not been undertaken to answer this question definitively, observational data suggest that in the presence of bilateral infiltrates, unilobe sampling is sufficient and minimizes risk of lavage volume and duration of bronchoscopy [ ] . the host response makes up the crucial second component of any infection syndrome, and therefore host biomarkers can be of use in diagnosing infection in ards. laboratory hematological features of inflammation, including leucocytosis, neutrophilia and elevated c-reactive protein, are not specific to infection and can occur in sterile precipitants of ards [ ] . the inflammatory response in pneumonia is highly compartmentalized and alveolar cytokines and other alveolar markers are the most discriminant for pneumonia (table ) [ ] . notably, although alveolar cytokines demonstrated excellent assay performance, measurement of pulmonary cytokines did not alter antimicrobial prescribing in a recent randomized trial [ ] . this illustrates that the challenges in diagnosis lie not only with the technology, but also the behavioral response to results. peripheral blood markers have the advantage of avoiding the need for bronchoscopic sampling and are therefore easier to obtain; however, they are generally less able to discriminate pneumonia from other infections table summary of host-based biomarkers for diagnosis of pneumonia in ards ards acute respiratory distress syndrome, rct randomized controlled trial, strem soluble triggering receptor expressed on myeloid cells, vap ventilator-associated pneumonia, hla human leukocyte antigen interleukin- /interleukin- validated in multi-center cohort [ ] but did not influence practice in an rct [ ] strem- initial report, but not validated in follow-up study [ , ] exhaled breath markers experimental with technical variation currently limiting implementation [ ] pentraxin- meta-analysis suggested alveolar levels superior to plasma levels with moderate diagnostic performance, no rct testing influence on practice [ ] and many lack sensitivity and or specificity for infection (table ). in summary, the diagnosis of pulmonary infection in ards is challenging, and existing techniques are imperfect and risk both inadequate and overtreatment. a combination of clinical, biological and radiological assessment, combined with microbiological sampling from the lungs, remains the current gold standard (fig. ) . the development of molecular diagnostics focusing on both host and pathogen offers great promise, but their impact on patient management and outcomes remains to be convincingly demonstrated. the most common bacterial causes of vap include enterobacterales, pseudomonas aeruginosa, staphylococcus aureus, and acinetobacter among the general population of mechanically ventilated patients [ ] . the pathogens associated with vap in ards are similar to those seen among non-ards patients who develop vap (fig. ) [ , , ] . moreover, patients with ards undergoing extracorporeal membrane oxygenation (ecmo) demonstrate the same breakdown of pathogens with pseudomonas aeruginosa and staphylococcus aureus predominating [ ] . one important element, regardless of the specific causative bacteria seen in vap, is that antibiotic resistance is increasing in vap as well as in other nosocomial infections. in , the tigecycline evaluation and surveillance trial described important european changes in antimicrobial susceptibility between and , with increases in the rates of esbl-positive escherichia coli (from . to . %), mdr acinetobacter baumannii complex (from . to . %), esbl-positive klebsiella pneumoniae (from . to . %), and methicillin-resistant staphylococcus aureus (mrsa) (from . to . %) [ ] . similar worrisome trends for bacterial susceptibility to available antimicrobials have been reported by other investigators as well [ , ] . most worrisome is the increasingly recognized presence of resistance to new antibiotics specifically developed to treat vap [ ] . prior antibiotic exposure and subsequent changes in the host's airway microbiome due to dysbiosis seem to drive the prevalence of antibiotic-resistant bacterial causes of vap (fig. ) [ , ] . the presence of invasive devices such as endotracheal tubes and antibiotic administration promote pathogenic bacterial colonization due to the overwhelming of local defenses, resulting in the development of an intermediate respiratory infection termed vat [ ] . vat represents a compartmentalized host response associated with a better overall prognosis compared to vap, but vat can prolong the duration of mv and icu length of stay [ ] . if the aforementioned response is not compartmentalized, progression to vap is likely and potentially other organ failure including ards may occur [ ] . one of the major fears concerning nosocomial pulmonary infections in ards at the present and into the future is the increasing presence of novel pathogens and infections with microorganisms for which limited treatment options exist. as we increasingly treat older and more immunocompromised hosts with ards, the likelihood for emergence of novel pathogens and infection with pan-resistant microorganisms will increase. early identification of such emerging pathogens in ards is critical. the importance of early identification of novel pathogens is necessary to facilitate epidemiologic surveillance, curtailing pathogen spread, and providing early treatment as illustrated by recent nosocomial outbreaks of middle eastern respiratory syndrome coronavirus, sars-cov- and pan-resistant escherichia coli [ ] [ ] [ ] [ ] . in the future, metagenomic next-generation sequencing should allow earlier and more targeted treatments for novel pathogens causing ards or complicating the course of patients with ards. such technology will allow earlier pathogen identification and accelerate the workup and treatment for both infectious and noninfectious causes of diseases complicating ards [ ] . although the majority of respiratory infections in ards patients are caused by bacteria, icu-induced immunoparalysis may induce infection with unusual pathogens. although invasive pulmonary aspergillosis (ipa) has been reported mainly in immunocompromised patients, lower respiratory tract colonization with aspergillus has been more frequently associated with ards than in other patients invasively ventilated in icu [ ] . the mechanism of damage involves the combination of alveolar damage (induced by ards) and a dysregulation of the local immune response, together with sepsis-induced immunosuppression, innate immunity and antigen presentation impairment, accounting for the development of ipa in previously colonized patients [ , ] . co-infection with influenza has been reported as a risk factor for ipa [ ] . contou et al. reported isolation of aspergillus in the lower respiratory tract in almost % of patients with [ ] . bar graphs depicting the percentages of the most frequently isolated microorganisms in icu-acquired pneumonia episodes for (red bars) and for patients with acute respiratory distress syndrome (ards) (blue bars). total number of isolates , and , respectively ards ( % had putative or proven ipa) [ ] . an important finding from this study was that the median time between initiation of mv and first sample positive for aspergillus spp. was only days. moreover, a post-mortem study in ards patients found that % of deceased patients had ipa manifestations [ ] . if aspergillus is identified as a pathogen in an immunocompetent patient, it is recommended to screen for any kind of immunosuppression (humoral, cellular or combined, complement, etc.). viruses may also be responsible for infection in ards patients. because of immunoparalysis following the initial pro-inflammatory response to aggression, latent viruses such as herpesviridae may reactivate in icu patients [ ] . hsv and cmv are frequently recovered in lung or blood of icu patients (up to %, depending on the case mix), their reactivation being associated with morbidity and mortality [ , , ] . however, the exact significance of these reactivations is debated: these viruses may have a true pathogenicity and cause lung involvement [ , ] , thereby having a direct role in morbidity/mortality observed with their reactivation; or they may be bystanders, their reactivation being only secondary to disease severity or prolonged icu stay. to date, the answer is not known, data regarding a potential benefit of antiviral treatment being controversial. for hsv, the most recent randomized control trial found no increase in ventilator-free days in patients having received acyclovir, but a trend toward lower -day mortality rate (hazard ratio for death within days post-randomization for the acyclovir group vs control was . ( % ci . - . , p = . ) [ ] . for cmv, two recent randomized clinical trials (rcts) were performed: the first one showed that valganciclovir prophylaxis in cmv-seropositive patients was associated with lower rate of cmv reactivation as respiratory microbiome dysbiosis is also demonstrated as a prerequisite for most cases of vap and vt compared to placebo, but not with better outcome [ ] ; and the second one showed that, as compared to placebo, ganciclovir prophylaxis did not lead to lower il- blood level at day , but patients having received ganciclovir had trend toward lower duration of mv [ ] . besides latent viruses, respiratory viruses (rhinovirus, influenza, adenovirus…) have been recently found to be responsible for nosocomial infection in ventilated or non-ventilated patients [ ] . however, like herpesviridae, their true impact on morbidity/mortality is not known. in summary, hsv and cmv may cause viral disease in ards patients, and respiratory viruses may be responsible for hospital-acquired pneumonia; however, the true impact of these viral infections on outcomes remains to be determined. veno-venous extracorporeal membrane oxygenation (vv-ecmo) is now part of the management of refractory ards [ , ] . these very sick patients are at high risk for developing typical icu-related nosocomial infections (e.g., vap or bloodstream infections), in addition to ecmo-specific infections, including localized infections at peripheral cannulation insertion sites. bizzarro et al. reported a high prevalence rate of nosocomial infection of % in a large international registry of ecmo patients [ ] , pulmonary infection being the most frequently reported. this high prevalence may be explained by underlying comorbidities, concomitant critical illness, prolonged mechanical support, mv and icu stay as well as impairment of the immune system by the extracorporeal circuitry through endothelial dysfunction, coagulation cascade, and pro-inflammatory mediators release [ ] . while the rate of pulmonary infection on ecmo has not been thoroughly compared with a population with the same critical illness but in the absence of ecmo, vap was reported in out of patients receiving ecmo ( % vv-ecmo) by grasseli et al. [ ] . among patients who underwent va-ecmo for > h and for a total of ecmo days, ( %) developed nosocomial infections, corresponding to a rate of . infectious episodes per ecmo days. vap was the main site of infection with episodes occurring in patients after a median ± standard deviation of ± days [ ] . vap and resistant organisms are therefore common in that population [ ] [ ] [ ] . the duration of ecmo has been frequently associated with a higher incidence of vap [ , ] , even if a causal relationship is impossible to establish. indeed, longer ecmo runs could be a direct consequence of infectious complications rather than a risk factor. however, it seems clear that ecmo patients who acquired vap had longer durations of mv and ecmo support and a higher overall icu mortality [ , , ] . similarly, immunocompromised patients and older age were consistently found as risk factors associated with infections on ecmo [ , ] . the clinical diagnosis of pulmonary infection in ecmo patients is challenging, since they may have signs of systemic inflammatory response, possibly triggered by the ecmo itself, whereas fever could be absent if the temperature is controlled by the heat exchanger on the membrane. in addition, the common application of an ultraprotective ventilation aiming to rest the lung on vv-ecmo and frequent pulmonary edema on va-ecmo make the interpretation of new infiltrates on chest-x ray, which are commonly used to suspect a vap, difficult. beyond the diagnosis challenge of pulmonary infection on ecmo, the changes of pharmacokinetics/pharmacodynamics (pk/pd) of antimicrobial agents could also contribute to delaying appropriate antimicrobial treatment and consequently increase the burden of infections. an increase in the volume of distribution by ecmo as well as the severity of the underlying illness and drug clearance impairment through renal or liver dysfunctions complicates the management of antibiotics and antifungal therapies [ ] . while waiting for large in vivo studies aiming to report the respective pk/pd of antimicrobial agents on ecmo, avoiding lipophilic agents (i.e., more likely sequestrated on the ecmo membrane) [ ] and therapeutic drug monitoring are warranted. apart from bacteremias/fungemias, most infections are in interstitial or tissue spaces and hence the efficacy of a drug should be related to drug concentrations and actions in those tissues [ ] . drugs will cross the body membranes (move from intravenous compartment into tissue compartments) if there is an intrinsic "carrier mechanism", or if the compound is either a small molecule or is lipophilic [ ] . hydrophilic antimicrobials are found in extravascular lung water, but for relevant lung tissue penetration the lipophilic drugs are most important [ ] [ ] [ ] [ ] . large molecules such as vancomycin, teicoplanin, aminoglycosides and colistin will have poor lung tissue concentrations when given intravenously (elf/plasma concentration ratio << ) [ , ] . betalactams penetrate into lung parenchyma better than other hydrophobic antibiotics [ ] . elf/plasma concentration ratio for glycylcyclines (e.g., tigecycline) is around . lipophilic compounds such as macrolides, ketolides, quinolones, oxazolidinones, antifungals and antivirals will have good lung tissue concentrations (elf/plasma concentration ratio > ) after intravenous administration [ ] . oxazolidinones (linezolid), glycylcyclines (tigecycline) and sulfonamides (cotrimoxazole) may be effective in the treatment of mdr pathogens; however, there is no ards-specific lung pk (elf/plasma concentration) data for these drugs. although newer antimicrobials (ceftolazone-tazobactam, meropenem-vaborbactam, plazomicin) have activity against drug-resistant gram-negative pathogens, there are limited alternatives against drug-resistant acinetobacter baumaniii such as cefiderocol which is undergoing phase clinical trials. the advent of newer generation of delivery devices and mdr organisms has led to a renewed interest in the field of nebulized antimicrobials [ ] , although recent trials in pneumonia have failed to demonstrate clinical benefits [ , ] . ards is often associated with multiple organ dysfunction syndrome. hence, the possibility of achieving high intrapulmonary concentrations with limited systemic side effects is appealing. although recent wellconducted rcts argued against systematic use of nebulized antimicrobials in nosocomial pneumonia [ , ] it may still have a place in the treatment of severe lung infections due to mdr bacteria. in this view, selecting the correct antimicrobial formulation and dosing (table ) is an essential first step, as well as the best device, namely vibrating mesh nebulizer [ ] . clinical pk data available for some nebulized antibacterial, antiviral and antifungals confirm high pulmonary and low systemic exposure [ ] . sputum pk studies report high variability and are difficult to interpret [ ] . however, lung deposition of nebulized antimicrobials is influenced by many factors, including specific ventilator settings. ventilator settings and procedures usually recommended for improving aerosol delivery (high tidal volume, low respiratory rate and low inspiratory flow, systematic changes of expiratory fil-ters…) are difficult to implement in patients with ards, at least those with the most severe forms. ards is a heterogeneous lung condition causing inhomogeneous ventilation distribution potentially affecting drug delivery at the affected site. increased lung inflammation can also increase systemic concentrations by increased diffusion across the alveolo-capillary barrier, thus influencing the nebulized drug dosing [ ] . further pk studies investigating nebulized antimicrobial in ards are required for recommending dosing regimens in this condition. areas of investigation such as pulmonary nanomedicine and targeted delivery using intracorporeal nebulization catheter, while still investigational, have the potential to overcome many of these barriers and enhance lung tissue antimicrobial concentrations [ ] . nosocomial infections may contribute to the mortality related to ards given that such infections are responsible for worsening hypoxemia and causing sepsis. as such, the prevention of these infections must be reinforced to avoid straining the prognosis of patients suffering from ards. however, interpreting the vap prevention literature in this context is challenging because ( ) no studies have been conducted expressly in ards patients; ( ) several preventive measures have been shown to reduce the rate of pulmonary infection, but many less have demonstrated an impact on patient prognosis [ ] . that being said, the general strategy for preventing pulmonary infection applies also in ards patients. however, some preventive measures deserve a special focus in the context of ards patients (fig. ) : ( ) oral care with chlorhexidine is suspected to worsen respiratory failure; ( ) selective digestive decontamination (sdd) deserves to be discussed in such high-risk patients, as it has been proven to be effective in reducing mortality in icu patients and likely lowers vap rates. there is no single preventive measure that will completely avert pulmonary infection in patients suffering from ards and patients must be approached with a package or bundle of preventive measure [ ] provided that an early weaning strategy is part of the bundle [ ] . other preventive measures and notably some expensive medical devices such as automated endotracheal tube cuff pressure monitoring or endotracheal tube allowing subglottic secretion drainage have not been proven effective on patient's outcomes (mortality, duration of mv, antibiotic use), but could be dedicated to these high-risk patients. however, translating research into an efficient bundle of care to prevent pulmonary infection remains a challenge and behavioral approaches to implement the measures are as important as the measures themselves [ ] . chlorhexidine-gluconate (chg) use for oral care in icu patients may be harmful despite previous consistent data showing its beneficial effect in preventing vap [ ] . oral mucosa adverse events with % (w/v) chg mouthwash in icu are frequent, but often transient. adverse events described were erosive lesions, ulcerations, plaque formation (which are easily removed), and bleeding mucosa in of patients ( . %) who received % (w/v) chg [ ] . a systematic review and meta-analysis by labeau et al. in evaluated the effect of oral decontamination with chx [ ] . twelve studies were included (n = ). overall, chx use resulted in a significant risk reduction of vap (rr = . , % ci . - . , p = . ). favorable effects were more pronounced in subgroup analyses for % chx (rr = . , % ci . - . ) and for cardiosurgical patients (rr = . , % ci . - . ). however, a recent metaanalysis suggested that oral chg paradoxically increased the risk of death, which may have resulted from toxicity of aspirated chg in the lower respiratory tract [ ] . consequently, it remains unclear whether using chg for oral care affects outcomes in critically ill patients. selective digestive decontamination (sdd) remains definitely a matter of controversy [ ] . on one hand, it reduces the mortality in mechanically ventilated patients, while on the other hand its use is limited by the potential fig. prevention of pulmonary infections in ards patients: from highly recommended preventive measures to a cautious or even a not recommended use of inducing more bacterial resistance. however, in ards patients at high risk of mortality with high level of bacterial resistance, sdd deserves to be evaluated. the better understanding of ards phenotype may offer an opportunity to develop more selective preventive measures in the future. pulmonary superinfections of ards patients considerably impact patients' prognosis. it is favored by altered local and systemic immune defenses. the poor outcome of ards with pulmonary superinfections is probably related to the lack of early accurate diagnostic methods and difficulties in optimizing therapy. this article reviewed the available knowledge and revealed areas for future investigations in pathophysiology, diagnosis, treatment and prevention. potentials for improvements are numerous in all the fields: to improve knowledge about the host factors (both systemic and local) favoring superinfections. to identify early the disequilibrium between the host and the microbiota that may promote pneumonia in ards patients. to identify early criteria for suspicion of vap and vat. to determine the appropriate time to perform bacteriological samples, and in particular develop a morphological way to unmask areas of pneumonia at the bedside. to identify new diagnostic tests providing accurate and early diagnosis of pneumonia. to develop accurate early methods of pathogen identification and to distinguish patients infected and simply colonized (especially for viruses and fungi). to evaluate the impact of new molecular methods in diagnosing pneumonia in ards patients and improve prognosis. to evaluate the impact of tdm monitoring of antimicrobials on the prognosis of ards patients with pneumonia. to develop non-antibiotic therapies in the future, including vaccines, monoclonal antibodies and phage therapy. evaluate the benefit on antimicrobial consumption and prognosis of the use of sdd in ards patients in icus with a high level of bacterial resistance. acute respiratory distress syndrome changes in prevalence of health care-associated infections in us hospitals ventilator-associated pneumonia and icu mortality in severe ards patients ventilated according to a lung-protective strategy ventilator-associated pneumonia in ards patients: the impact of prone positioning. a secondary analysis of the proseva trial ventilator-associated pneumonia in adults: a narrative review the role of neutrophils in immune dysfunction during severe inflammation 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and perceptions throughout a multifaceted behavioral program aimed at preventing ventilator-associated pneumonia prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis oral mucosal adverse events with chlorhexidine % mouthwash in icu reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis antipathy against sdd is justified: yes soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia soluble triggering receptor expressed on myeloid cells- in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia the potential role of exhaled breath analysis in the diagnostic process of pneumonia-a systematic review diagnostic value of pentraxin in respiratory tract infections: a meta-analysis. medicine (baltimore) :e a biomarker panel (bioscore) incorporating monocytic surface and soluble trem- has high discriminative value for ventilator-associated pneumonia: a prospective observational study the current status of biomarkers for the diagnosis of nosocomial pneumonias maintenance treatment with inhaled ampicillin in patients with cystic fibrosis and lung infection due to methicillin-sensitive staphylococcus aureus use of inhaled ampicillin-sulbactam against multiresistant acinetobacter baumannii in bronchial secretions of intensive care unit patients aerosolized ceftazidime prophylaxis against ventilator-associated pneumonia in high-risk trauma patients: results of a double-blind randomized study aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by pseudomonas aeruginosa nebulized imipenem to control nosocomial pneumonia caused by pseudomonas aeruginosa levofloxacin inhalation solution (mp- ) in patients with cystic fibrosis with pseudomonas aeruginosa reduction of bacterial resistance with inhaled antibiotics in the intensive care unit aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit aerosolized tobramycin in the treatment of ventilator-associated pneumonia: a pilot study for nebulized antibiotics in ventilator-associated pneumonia ( ) ventilator-associated pneumonia caused by multidrug-resistant gram-negative bacteria: understanding nebulization of aminoglycosides and colistin inhaled aztreonam lysine for chronic airway pseudomonas aeruginosa in cystic fibrosis key: cord- - xzc uc authors: nan title: esicm wednesday sessions october date: - - journal: intensive care med doi: . /s - - - sha: doc_id: cord_uid: xzc uc nan power spectrums for vt and eadi are shown in fig. (ps and nava) for a typical patient. the enlarged section highlights how changes in eadi are highly synchronized with nava ventilation, but less so for ps. table ) and complications of mechanical ventilation ( table ) did not differ significantly between the two studied groups. introduction. high tidal volumes in mechanically ventilated patients with ards lead to baro/bio-trauma and increase mortality. also, it was recently shown that ventilation with high tidal volumes is a risk factor for ''acquired ards'' in a medical population. objective. we evaluated the impact of high tidal volumes after cardiac surgery. method. we analysed the prospectively recorded data of , consecutive patients who underwent cardiac surgery from to . we predefined groups of patients based on the tidal volume delivered immediately after surgery: ( ) low: - . , ( ) ''traditional'': - . , ( ) high: above ml/kg of predicted body weight (pbw). we assessed the risk factors for organ dysfunction (prolonged mechanical ventilation, hypoxemia, hemodynamic failure and renal failure) by univariate and multivariate analysis, including the initial tidal volume in the models. mean tidal volume/actual weight and tidal volume/pbw was . ± . and . ± . in men (p \ . ), . ± . and . ± . in women (p \ . ). patients ( %) were ventilated with low tidal volumes, , ( . %) with ''traditional'' tv and ( . %) with high tv. the mean body mass index in the groups was . ± . , . ± . and . ± . respectively (p \ . ). with increasing bmi, the tidal volume/ actual weight decreased while the tidal volume/pbw increased (figure) . the percentage of women was . , . and . % respectively for low, ''traditional'' and high tv (p \ . ). high tidal volumes were associated with prolonged intubation ([ h) ( . vs. conclusion. traditional and very high tidal volumes are associated with prolonged mechanical ventilation and organ dysfunction after cardiac surgery and use of high tidal volumes is an independent risk factor. ''prophylactic'' protective ventilatory strategy should be provided in this population with inflammatory state at risk to develop ventilator induced pulmonary edema. women and patients with high bmi are more at risk to be ventilated with injurious tidal volumes. introduction. evidence shows that clinicians' non-technical skills (behavioural and cognitive skills) have a significant impact on teamworking, patient safety, efficiency of care provided and potentially patient outcomes ( ) . such skills are key for cardiac arrest teams (cats), which are multi-professional (anaesthetists, physicians and nurses) and normally function under high pressure. to date, most tools to assess nontechnical skills in healthcare have focused on surgery ( ) and anaesthesia ( ) . no validated, robust tools are currently available for assessing non-technical skills in cats. objectives. to develop and validate an observational skill-based clinical assessment tool for resuscitation (oscar). this should be psychometrically robust for use in both training and assessment contexts. methods. oscar was based on a well-validated tool for surgery (otas) ( ) and was developed in phases. six behaviours were included in the assessment: communication, cooperation, coordination, monitoring, leadership and decision-making. observable behavioural exemplars were derived for each one of these behaviours across the three cat subteams-anaesthetists, physicians and nurses (phase ). quantitative expert consensus methodology was employed to assess content and face validity and observability of the exemplars (phase ). two clinician observers used oscar to blindly rate eight cats performance in a series of simulated cardiac arrests. psychometric analyses of these ratings were used to determine observable behaviour applicability, internal consistency, and inter-rater reliability (phase ). . of oscar behaviours demonstrated high internal consistency (cronbach a = . - . ). psychometric analyses dictated removal of three behavioural exemplars (two in anaesthetic group; one in physician group) to significantly improve internal consistency. inter-rater reliability was also high (inter-observer pearson r = . - . , all p \ . ). inter-observer reliability analyses revealed a learning curve between the two observers, with significant reduction in scoring discrepancies from the first to the eighth observed resuscitations. conclusions. oscar is a psychometrically robust (reliable, content-and face-valid) tool for the assessment of teamworking skills in cardiac arrest events. the tool is feasible to use and can be employed for both training and assessment purposes. introduction. different educational methodologies are used to teach basic skills in emergency medicine. high-fidelity patient simulation offers an ideal venue for presentation of critical events that can be managed by medical students without risk to a patient. therefore full scale simulation training could be superior to paper case based seminary rounds to achieve these specific educational objectives. objectives. the aim was to compare simulation to a standard education measured by multiple choice questionnaire. after written informed consent and approval of the institutional research ethics board fifth year medical students were included in the survey. they took part in the compulsory emergency medicine curriculum of charité universitätsmedizin berlin. the students completed a basic multiple question tests on day including questions concerning the topic of ''acute coronary syndrome'' (acs). on day for the topic ''acs'' half the group was assigned a min session simulation training while half the group was assigned a min session paper case training. on day groups were reversed and the topic ''aic'' was taught in either simulation training or paper case seminary round. the test of day was repeated after each training sessions. results of the tests were evaluated using spss(tm) . the mann whitney u test was used to show any significant differences in reaching educational objectives in the test (a \ . was considered significant). there was an even distribution of men and women among the two groups. the test results showed no significant difference between the two groups on day . on day two for the topic ''acs'' the group with simulation training achieved significantly better test results. for the topic ''acs'' on day there was no difference while students received further training in acs not using a high fidelity simulator. the results were not linked to specific teachers. introduction. rapid sequence induction (rsi) involves loss of spontaneous breathing and mandates airway control. steps to reduce adverse incidents include adherence to minimum monitoring standards, appropriate drug selection, access to difficult airway equipment and presence of skilled anaesthetists. there is substantial evidence that appropriate monitoring reduces risk by detecting the consequences of errors, and by giving early warning of patient deterioration. objectives. to assess conduct of emergency anaesthesia (monitoring and drugs) for critically ill patients not in an operating theatre (or) administered by intensive care doctors. methods. prospective analysis of rsi for critically ill patients in a uk nhs acute hospital over month. or based practice was excluded. reason for anaesthesia, location, drugs administered, monitoring modalities, adverse events and access to airway equipment were recorded. results. data from patient episodes were collected: predominantly in the emergency department ( %) and intensive care unit ( %) for respiratory failure ( %), reduced consciousness ( %) and to facilitate investigations ( %) . the most common induction agent was propofol ( %); thiopentone ( %) and etomidate ( %) were less frequently used. suxamethonium ( %) was preferred for initial neuromuscular blockade. during induction most doctors used pulse oximetry, electrocardiography and blood pressure monitoring. only % used capnography. no doctor used minimum monitoring to association of anaesthetists of great britain and ireland (aagbi) standards. rescue airway equipment immediately available is shown in fig. . complications occurred in cases (fig. ) . patients that had a hypotensive episode during induction all had thiopentone or propofol used as induction agents. % of patients had a period of desaturation, and % required more than one attempt for successful intubation. in cases with complications, rescue airway equipment was unavailable in[ and % did not achieve uk minimum monitoring standards. conclusions. shortcomings during emergency anaesthesia were recorded including monitoring, access to rescue airways and physiological disturbance. procedural guidelines and training are to be developed for emergency anaesthesia; access to capnography and alternative airway equipment will be assured. these issues are unlikely to be unique to our trust and assessment of practice is recommended. introduction. critical care echocardiography (cce) is performed and interpreted by the intensivist at the bedside to establish diagnoses and guide the management of patients with circulatory or respiratory failure in the icu. competence in basic and advanced cce has been recently defined [ ] , but no curriculum to reach the required cognitive and technical skills has yet been elaborated. objectives. to assess the efficacy of a limited, tailored training program for noncardiologist residents without experience in ultrasound to reach competence in basic cce. methods. six noncardiologist residents (anaesthesiology: n = , pneumology: n = ) without previous experience in ultrasound participated to the study during two -month periods. the curriculum consisted in h of didactics, h of interactive clinical cases and h of tutored hands-on. color doppler mapping was excluded from the training. after completion of the training program, all eligible patients underwent subsequently a transthoracic echocardiography (tte) performed in random order by a recently trained resident and an experienced intensivist with expertise in cce who was used as a reference. in each patient, the resident and the experienced intensivist answered binary ''rule in, rule out'' clinical questions covered by basic cce [ ] : global left ventricular (lv) size and systolic function (eye-ball evaluation of ejection fraction), homogeneous or heterogeneous lv contraction pattern, global right ventricular (rv) size and systolic function, identification of pericardial fluid and tamponade, and assessment of both the size and respiratory variations of the ivc. in case of undetermined interpretation, the corresponding clinical question was considered not addressed. the agreement between responses to clinical questions provided by the two investigators who independently interpreted the tte study at bedside was used as an indicator of effectiveness of the tested curriculum. proportion of graduates to work within a ''critical care'' setting. the level of support available to trainees may vary with local resources but risk management and national guidelines stipulate that close supervision is provided to junior doctors in high stake decisions and procedures until deemed competent at the relevant tasks . furthermore, substantial ongoing reduction in working hours places further limitations on training; both majors can impact adversely on junior doctors service output and experience. a modified delphi method was used years ago to design a task focused single-day course on the theoretical basis of critical care and provide lab-based training in delphi identified high risk procedures and interventions . objectives. assess the impact of the course on the following: trainee confidence and the start of the ''novice'' critical care post trainee performance in comparison to peers perceived educational benefit from their training post compared to peers methods. junior doctors attending the course were enrolled in the study and matched for graduation year and medical school to junior doctors who did not attend similar training prior to commencing their post. data was collected through anonymous standardized forms on the day of the course, first day of the job, end of week , week and months into the post. trainee confidence and self perceived competence were assessed on a ten point scale. in addition, trainees were requested to maintain a log of interventions: -ultrasound guided central venous catheter insertion, -arterial catheter insertion, -ventilation problem solving. candidates attending the course demonstrated greater confidence at multiple points within their post as well as higher performance, satisfaction and educational value scores. conclusions. critical care trainees benefit from a task focused orientation to the fundamentals of critical care before commencing first post in this setting. . enrolled patients in each group. no differences in age and gender. incidence of vap-study group . % compared to control group . % p value . . vap per , hospital days: control- . % compared to study- . % p value . ; average days in icu control- . compared to study- . , p value . ; average ventilated days, control- . compared to . , p value . ; average antibiotic use in days control- . compared to study- . , p value . . introduction. nosocomial infections are the most common in-hospital complications with high morbidity and mortality. educating healthcare professionals is an important prevention measure. objective. to analyze the impact of a nurse consultant team on nosocomial infections prevention in the icu, the improvement in prevention knowledge of the nurse staff, and its impact in the application of the prevention measures in the daily practice. methodology: the nurse referent team was constituted by nurses. the study subjects were all the staff icu nurses and all the patients admitted during pre and post-intervention phases. the study was conducted in our medical-surgical icu ( beds) in phases: pre-interventional ( / / - / / ) observational. record of the accomplishment of cdc recommended variables about mechanical ventilation associated pneumonia (vap) and catheter related bloodstream infection (cr-bsi) prevention measures. interventional ( / / - / / ) eight educational meetings with the nurses staff groups to teach the most important aspects of the nosocomial infections prevention. before and after lectures every nurses answered an anonymous questionnaire about their knowledge in those subjects. a poster with the most important reminders was place in every icu patient room. post-interventional ( / / - / / ) observational. new record of the same cdc pre-interventional variables. we compared the accomplishment of these variables before and after the interventional phase as well as the number of correct questionnaire answers. statistics were made with spss software. results. during the interventional phase % of the staff nurses attended the educational meetings. the number of correct answers increased significantly after the conference ( . vs. . % p \ . ). regarding to the daily practice, we observed a significant increase in the accomplishment in most of the variables (see table below), while in of them no improve was observed and in the improvement was not statistically significant. during the study period we observed a decrease in the incidence of vap ( . - . episodes/ , mv days) and cr-bsi ( . introduction. glucose variability has been found to be associated with mortality in critically ill patients, independent of mean glucose concentration [ ] . objectives. the aim of this analysis was to assess the impact of real time continuous glucose monitoring (cgm) on glucose variability in critically ill patients receiving intensive insulin therapy (iit). methods. this is the post-hoc analysis of a prospective, randomized, controlled trial [ ] . data of patients admitted to the icu either receiving iit according to a real time cgm system (guardian Ò , medtronic, northridge, ca, usa) (n = ) or according to an algorithm (n = ) with selective arterial blood glucose measurements (simultaneously blinded cgm) for h were analysed. insulin infusion rates were guided according to the same algorithm in both groups. mean glucose and standard deviation, as a marker of glucose variability, were calculated for the first h (glumean , glusd ) and for the whole study period (glu sd ). statistical comparison of parameters between study groups and between icu survivors (n = ) and non-survivors (n = ) was performed using student's t test. results. the variability of sensor glucose during the entire study period was comparable between the real time cgm group and controls ( . ± . vs. introduction. in the gastrointestinal tract, the gut flora which comprises several hundred grams of bacteria is crucially involved in host homeostasis through their metabolic, trophic, and protective activities. however, the immediate changes in the gut flora in critical illness following severe insults are unknown. objectives. to investigate the changes in the gut flora at an early phase of severe insult in critically ill patients. methods. fifteen patients who experienced a sudden and severe insult including trauma, out-of hospital cardiac arrest, and cerebral vascular disease were studied, along with healthy volunteers as the control group. two fecal samples were acquired from the subjects by swabs of the rectum within h after admission to the emergency room (day ). samples were serially collected from patients on day , , , , , and . samples were collected from control subjects. results. total bacterial counts, especially various obligate anaerobes and total lactobacillus, significantly decreased in comparison to those of the control subjects on day . in addition, on day , the total organic acid levels of the patients were significantly lower than those of the control subjects; particularly acetic acid, propionic acid, and butyric acid. the levels of these acids remained low throughout the days period of study. the total bacterial counts did not recover to normal levels during the day study period. obligate anaerobe counts of the patients did not improve until day . total lactobacillus counts were low on day and increased gradually thereafter, but did not attain the levels found in controls. the counts of pathogens (enterococcus and pseudomonas) increased during the study period. conclusions. gut flora in critically ill patients can change drastically immediately after a severe insult, and may not recover for up to days. at the same time, the number of harmful bacteria can increase. total bacteria . ( . - . ) . ( . - . ) . obligate anaerobes clostridium cocades group . ( . - . ) . ( . - . ) . clostridium leptam subgroup . ( . - . ) . ( . - . ) . bacteroides fragilis group . ( . - . ) . ( . - . ) . bifidobacterium . ( . - . ) . (\ . - . ) . atopobium cluster . ( . - . ) . (\ . - . ) . results. mean serum (oh)d level was . ± . ng/ml. by current definitions the majority of patients ( . %) were vitamin d deficient (\ ng/ml) and . % were vitamin d insufficient (c and \ ng/dl). normal (oh)d levels ([ ng/ml) were present in . %. table provides information on clinical and laboratory findings in the three (oh)d groups. both lower (oh)d tertiles were associated with increased hospital mortality after adjustment for age, sex and saps ii. for patients both (oh)d and pth levels were available. adjusting the cox regression analysis also for pth and dialysis status increased the hr for hospital mortality to . ( . - . ) and . ( . and . ) for the two lower (oh)d tertiles. in addition tertiles of pth and serum calcium levels suggested higher mortality rates for patients in the highest pth (p = . ) and those in the lowest calcium tertile (p = . ). our results demonstrate that independent of baseline saps ii, age and sex, critically ill patients with low (oh)d levels seem to be at increased risk for hospital mortality. whether a rapid correction of vitamin d status may be beneficial in the icu setting remains to be further explored in randomized controlled trials. • the autonomic storm after brain death must be early diagnosed and treated with a standardized protocol including hormone therapy introduction. the use of filling pressures of the right atrium and left atrium is normal in the monitoring of critically ill patients undergoing mechanical ventilation. this monitoring is done through an invasive catheter placed in the superior vena cava and pulmonary artery, which is not free of complications. the ability to make measurements of these parameters in a non invasive way, makes the echocardiography an useful and essential tool when monitoring critically ill patients objectives. we focus the study on validate the reliability of noninvasive measurements by echocardiography and invasive measurement catheters of filling pressures methods. we conducted a prospective observational study relating the filling pressures, between central venous pressure (cvp) with the diameter of the inferior vena cava and left atrial pressures with the values of the ratio e/e . the filling pressure variables were only discriminated as high or low. low values were accepted when invasive measurement of cvp was \ and \ mmhg in the lap; and by echocardiography when the diameter of the ivc was\ mm and the ratio e/e \ . high values were accepted when the measurement of cvp was higher than and mmhg in lap and in echocardiography when the diameter of the ivc [ mm and the ratio e/e [ . we collected data from patients in the immediate postoperative period, under mechanical ventilation (vt - ml/kg, fio %, peep ), sinus rhythm, good cardiac function and without postoperative drug support. all of them had a central venous line and right atrium catheter as habitual monitoring of postoperative cardiac patients. we performed an echocardiography when the patient presented hypotension, with low values of cvp and lap, and we repeated the measurements after the infusion of the habitual fluid protocol ( ml hes % in - min). the data we record were: diameter of ivc and ratio e/e by echo and cvp and lap values by invasive catheters. rd esicm annual congress -barcelona, spain - - october s introduction. an attenuated cardio-hemodynamic response to dobutamine is associated with a poor outcome in established human sepsis [ , ] . establishing a sensitive method to identify early cardiac dysfunction in both experimental and human sepsis would be a useful tool to explore timesensitive mechanisms further. objectives. to assess myocardial responsiveness to dobutamine in early sepsis. methods. all procedures were in accordance with uk home office laboratory animal legislation. under isoflurane anaesthesia, male adult wistar rats underwent left common carotid and right internal jugular venous cannulation for blood sampling/continuous bp monitoring and fluid administration respectively. rats received either . ml caecal slurry (sepsis; n = ) or . ml saline (sham; n = ) ip, before fluid resuscitation ( . % saline ml/kg/h) and conscious monitoring was commenced. after h, rats were re-anaesthetized with isoflurane and transthoracic echocardiography was performed. stroke volume was optimised with saline boluses prior to an incremental dobutamine infusion ( . - mcg/kg/ min). data are presented as mean (sd); analyzed with -way anova and post-hoc tukey test. results. figure summarizes hemodynamic changes after sepsis, fluid resuscitation and dobutamine infusion. baseline parameters were similar after echocardiography-guided fluid resuscitation, with contractility and stroke volume restored in septic rats to sham values. septic rats demonstrated an enhanced chronotropic response to dobutamine compared to sham (p \ . ). both peak velocity and cardiac output were attenuated by c % in sepsis (p \ . ). in sepsis, baseline map was higher but neither sham nor septic maps were affected by dobutamine infusion. conclusions. dobutamine stress echocardiography is a sensitive, reproducible, dynamic physiological probe that reveals early cardiac dysfunction in septic rats with apparently similar baseline cardiovascular physiology. introduction. the evaluation of right ventricular (rv) function is clinically useful in patients with acute respiratory distress syndrome (ards) because the presence of rv failure has large prognosis implications. the purpose of the current study was to compare right ventricular myocardial strain imaging parameters with conventional echocardiographic indices evaluating right ventricular function during ards. objectives. we hypothesized that peak systolic strain would be more sensitive than conventional echocardiographic parameters in detecting subclinical right ventricular systolic dysfunction in patients with ards. methods. in total, patients with ards and with normal right ventricle function assessed by two dimensional echocardiography and age matched subjects under mechanical ventilation without heart or pulmonary disease were included in the present study. conventional echocardiography parameters for rv function assessment like rv fractional area change (rvfa) or the tricuspid annular plane systolic excursion (tapse) were measured and compared to tissue doppler imaging parameters with strain value obtained from the right ventricle free wall. . strain values were reduced in the rv free wall of the patients with ards compared with the control group ( . % ± . vs. . % ± . p = . ) moreover no significant difference was observed in conventional two dimensional parameters evaluating rv systolic function between these two groups of patients. in patients with ards a significant relationship was shown between peak systolic strain at basal free wall and arterial carbon dioxide tension (rho = - . p = . ) and with the end inspiratory pressure (rho = - . p = . ). conclusions. during the ards, doppler tissue imaging parameters can determine rv dysfunction that is complementary to conventional echocardiographic indices and is correlated with respiratory parameters. on doppler tissue imaging, patients with ards exhibit abnormal rv systolic function even in patients with normal rv function assessed with conventional echocardiographic parameters. objectives. studying the effect of olv on rv outflow impedance during inspiration and expiration using transesophageal echo-doppler in a trial to differentiate the rv consequence of increasing lung volume from those secondary to increasing airway pressure during mechanical ventilation. methods. thirty stable patients on mechanical ventilation because of different causes were enrolled prospectively in this single center, cross sectional clinical study. each patient was firstly subjected to conventional ventilation (cv) with volume controlled ventilation, followed by open lung concept (olc) ventilation by switching to pressure controlled mode, then recruitment maneuver applied until pao /fio [ torr. hemodynamic (mean arterial pressure ''map'', central venous pressure ''cvp'' and heart rate ''hr'') and respiratory (total and intrinsic peep, peak, plateau and mean airway pressure and total and dynamic lung compliance) measurements were recorded before, min after a steady state of cv and min after a steady state of olc ventilation. also, transesophageal echo doppler was performed at end of inspiration and end of expiration to calculate the mean acceleration (ac mean ), as a marker of the rv outflow impedance, min after a steady state of cv and min after a steady state of olc ventilation. results. during inspiration, ac mean was significantly lower during cv compared to olc ventilation (p value . ). inspiration didn't cause a significant decrease in acmean compared with expiration during olv (p value. ) but did do so during cv. in comparison to baseline and cv, olc ventilation was associated with a statistically significant higher cvp (p value . for both), higher total quasi-static lung compliance (p value . for both) and dynamic lung compliance (p value . for both). moreover, pao /fio ratio of olv was significantly higher than in baseline and cv (p value . for both). conclusions. olc ventilation does not change rv afterload during inspiration and expiration as rv afterload appears primarily mediated through the tidal volume. moreover, olc ventilation provide a more stable hemodynamic condition and better oxygenation and lung dynamics. introduction. among indices provided by the analysis of aortic blood flow through esophageal doppler, mean acceleration (acc) is supposed to reflect the left ventricular (lv) systolic function, but this has been poorly validated. in particular, acc could be influenced by loading conditions of the lv. objectives. to test whether acc actually behaves as an indicator of lv systolic function by testing if . it increased with inotropic stimulation, . it was not altered by fluid loading, . it correlated with the echographic lv ejection fraction (lvef) and it reliably tracked the changes in lvef during therapeutic intervention. in patients with cute circulatory failure (sapsii ± , age ± years, receiving norepinephrine), we administered either a volume expansion ( ml saline over min in patients) or dobutamine ( lg/kg/min in patients). we simultaneously measured acc (cardioq, deltex medical) and lvef at baseline and after therapeutic intervention. results. volume expansion significantly altered neither lvef (from ± to ± %) nor acc (from . ± . to . ± . cm/s ) while dobutamine infusion significantly increased lvef by ± % and acc by ± %. considering the acc/lvef pairs of measurements, an acc \ . cm/s predicted a lvef b % with a sensitivity of % ( % ci [ - %]) and a specificity of % ( % ci [ - %]). the changes in lvef and in acc during fluid and dobutamine administration were significantly correlated (r = . , p \ . ). conclusions. acc fulfilled the criteria required from a clinical indicator of lv global systolic function. a given value of acc allowed detecting a low lvef with a modest accuracy. by contrast, the treatment-induced relative changes in acc were reliable for tracking the treatment-induced relative changes in lvef. objectives. to compare the relationship between systolic or diastolic dysfunction at icu admission and the incidence of cardiologic complications and mortality at sixth months. methods. prospective study of forty consecutive patients diagnosed of acute myocardial infarction (ami) ( nstemi, stemi) who were admitted in the icu of university hospital puerto real (cadiz, spain) from st may to th september . studied variables: age, gender, type of ami (nstemi, stemi), left ventricular ejection fraction (lvef) by biplanar simpson's rule, diastolic function (ratio e/e of the mitral annulus included), incidence of cardiac complications (acute pulmonary oedema, atrial fibrillation with hemodynamic instability and cardiogenic shock) and mortality at sixth month. echocardiographic studies were performed with a ge vivid pro(r) by an intensivist who had performed up to doppler studies in critical patients. all studies were remeasured by a second observer in an echocardiographic workstation with no statistical difference in measured velocities. patients were classified according to their lvef in (a) preserved ([ %), (b) mildly depressed ( - %), (c) moderately depressed ( - %) and (d) severely depressed (\ %); and according to their e/e ratio in (a) normal e/e ratio (\ ) and (b) elevated e/e ratio (c ). the results were statistically analysed with chi-square test and odds ratio calculus. results. diastolic dysfunction measured with e/e ratio was associated with high incidence of cardiac complications (chi test cl % p \ . , or ). systolic dysfunction measured by lvef was also associated with more complications but with less strength of statistical association (chi test cl % p \ . , or . ). there were no significative statistical difference between lvef and e/e ratio in mortality at sixth month. conclusions. in our study, diastolic and systolic dysfunctions in patients with ami at icu admission were associated with high incidence of cardiac complications, with more strength of statistical association in patients with diastolic dysfunction. the small sample volume didn't allow us obtaining significative statistical differences in mortality at sixth months. a new method has been developed to assess global end-diastolic volume (gedv) and extravascular lung water (evlw) from a transpulmonary thermodilution curve. our goal was to compare this new method to the established method currently in clinical use, over a wide range up to extreme pathophysiological conditions. objectives and methods. anesthetized and mechanically ventilated pigs ( - kg) were instrumented with a central venous catheter and a right ( f pulsiocath, pulsion, munich, germany) and a left ( f volumeview, edwards lifesciences, irvine, ca) thermodilution femoral arterial catheter. the right femoral catheter was connected to a picco monitor (pulsion) and used to measure cop, gedvp and evlwp using the old method based on the equation: gedv = cop (mtt -dst). the left femoral catheter was connected to the new ev monitor (edwards) and used to measure coe, gedve and evlwe using the new method based on the equation: gedve = f (s /s ) coe mtt, where s and s are respectively the maximum up-and down-slopes of the dilution curve, respectively. measurements were done during inotropic stimulation (dobu), during hemmorhage (hypo), during fluid overload (hyper), and after inducing oleic acid-acute lung injury (ali). overall, cop and coe ranged from . to . and from . to . l/min, respectively. cop and coe were closely correlated (r = . ), mean bias (± sd) was . ± . l/min and %error was %. gedvp and gedve ranged from to , and from to , ml. gedvp and gedve were closely correlated (r = . ), mean bias was - ± ml and %error was %. evlwp and evlwe ranged from to , and from to , ml. evlwp and evlwe were closely correlated (r = . ), mean bias was - ± ml and %error was %. parameters over the study period are presented in the table (*p \ . intervention vs. base or hyper). introduction. fluid resuscitation is a major therapy in icu. various mechanisms are involved in the regulation of the microcirculation and the macrocirculation. objectives. the goal of this study is to assess the sublingual microcirculatory changes in response to fluid challenge in preload-responsive and non preload-responsive patients. after approval by our local institutional review board, patients in surgical icu have been included in an observational study. each patient was monitored by an arterial catheter and an oesophageal doppler. the decision of fluid infusion was taken by the physician in charge of the patient. preload-responsive patients were defined by variations in cardiac index (ci) c %. sublingual microcirculation videos were obtained using the orthogonal polarized spectral (ops) imaging technology. functional capillary density (fcd, cm cm - ) and microcirculatory flow index (mfi) were collected. the macrocirculatory and microcirculatory measurements were obtained before, during and after the infusion of ml of saline. five sublingual sites were recorded before and after the fluid resuscitation. the ventilator settings and sedative and vasoactive drugs infusion rates were kept constant throughout the procedure. results. patients were admitted in icu for acute brain trauma (n = ), hemorrhagic shock (n = ), septic shock (n = ), acute brain hemorrhage (n = ) and acute pancreatitis (n = ). the average age of the patient was ± . the mean values of ci and mean arterial pressure (map) before the fluid therapy were respectively . ± . l/min/m and ± mmhg. nine patients responded to fluid infusion (ci c %.). about the microcirculation, there was no significant difference between responders (r) and non-responders (nr) concerning the variations of mfi ( . introduction. passive leg raising (plr) was shown to discriminate hemodynamically unstable patients who will benefit from subsequent fluid administration or not. concerned by the possibility of harmful hypotension starting the plr maneuver from a °semirecumbent position, in a previous study, we found that raising patients' legs from a supine position, we were not able to predict fluid responsiveness in a heterogeneous cohort of medical intensive care unit (icu) patients. objectives. to investigate whether starting plr maneuver from a °semirecumbent position would better predict volume responsiveness without harmful hypotension in spontaneously breathing critically ill medical icu patients. methods. fluid responsiveness was tested in consecutive patients ( sepsis, respiratory failure, heart failure, others) with a mean arterial pressure (map) \ mmhg and/or a cardiac index (ci) \ . l/min/m . heart rate (hr), mean arterial pressure (map), global end-diastolic volume index (gedvi), cardiac index (ci) and stroke volume index (svi) were recorded using the picco method. patients were stable in a semirecumbent ( °) position when first measurements were taken (baseline ). for the plr maneuver, patient's bed was tilt to have the lower limbs raised to a °angle while the patient's trunk was then in a supine position. changes after min were recorded. the patient was then brought into a supine position, and heamodynamic measurements were recorded when stable (baseline ). thereafter, ml of . % nacl were administered over min. positive predictive values (ppv) and negative predictive values (npv) of the plr maneuver were calculated using a cut-off value of % increase for ci and svi and % increase for map. results. patients' median age was ( - ) years and their saps score ( - ). all patients received vasopressors and/or inotropes. baseline hemodynamics and changes after plr and fluid challenge are shown in table . results are given as median (range); n/a = not available, *p \ . versus baseline. ppv and npv for ci were and %, for svi and % and for map and %, respectively. conclusions. in our hands, plr was not useful identifying fluid responders in this heterogenous population of severely ill medical icu patients, the starting semirecumbent position being associated with a potentially harmful decrease in map. however, it was helpful to detect patients who will not benefit (or even suffer harm) from further fluid administration. recently, some studies suggested that an impaired diastolic function is a predictive factor of mortality in patient with shock. it is not already known whether fluid infusion could improve diastolic function. objectives. the aim of the study was to determine the impact of rapid fluid infusion on diastolic function. after acceptance by the local ethic committee, icu patients were prospectively included. volume expansion (ve) by ml of saline was performed by the intensivist in charge. transthoracic doppler echocardiography was performed before and after fluid infusion. stroke volume (sv), early diastolic transmitral velocity (e), early diastolic mitral annular velocity (ea) and e/ea ratio (reflect of lv filling pressure) were studied. patients were divided in groups according to their sv' increase: responders (r) (those who increased their sv by at least %) and non-responders (nr). wilcoxon rank sum test was performed to compare data before and after ve. data are presented in median (iqr) results. fifty-three ( %) patients were r and ( %) were nr. in the overall population, ea increased significantly with ve [from . ( . ) to . ( . ) cm/s, p = . ]. in the r group ea increased significantly [from . ( . ) to . ( . ) cm/s, p = . ] and e/ea did not change significantly [from . ( . ) to . ( . ), p = . ]. however in the nr group, ea did not change significantly [from ( ) to . ( . ) cm/s, p = . ] while e/ea increased significantly [from . ( . ) to . ( . ) cm/s, p = . ]. conclusions. according to these results, adequate fluid infusion seemed to enhance lv relaxation without increasing lv filling pressure while inadequate fluid infusion did not affect relaxation but increased lv filling pressure. objectives. the aim of our study is to compare the rapid variation of co measured by vigileo-flotrac Ò with doppler-echocardiography which is considered as a reference method. during the first hours of hospitalisation, we studied mechanically ventilated patients receiving norepinephrine who underwent arterial pressure monitoring via a radial artery catheter. the flotrac Ò pressure sensor and the vigileo Ò monitor were connected to the arterial line. at each fluid expansion or norepinephrine dose modification a transthoracic doppler-echocardiography was performed and co was calculated. variations for co measured by each method were compared. results are presented as median (iqr). linear regression and the bland-altman method were used for statistical analysis. methods. for the in vitro experiments blood of healthy donors was incubated (in the ratio : ) with one of the following solutions: ringer solution, ringer-lactate solution, modified gelatin (gelofusin); hydroxyethyl starch (hes) / . . after incubation, the following parameters of erythrocyte aggregation were measured: t and t -characteristic times of spontaneous erythrocyte aggregation; b-hydrodynamic strength of aggregates; i . -index of strength of the largest aggregates at shear rate . s - . rbc deformability at various shear stresses was determined by ektacytometry. in vivo study on patients with trauma treated randomly with either only crystalloids (group ; n = ), or crystalloids + hes / . (group ; n = ) or crystalloids + gelofusin (group ; n = ) over days, the same parameters as in vitro study were determined at day - . twenty healthy men and women were included as controls. for statistical analysis the statistical package spss version . was used. statistical significance was considered at p \ . . in vitro study in the final analysis effects of different colloids on rbc aggregation and deformability were considered as increasing impact (:), decreasing impact (;) and no impact (-) ( table ) . in vivo study significant microrheological disturbances were detected at day after admission. deformability index was lower in patients compared with controls ( . ± . vs. . ± . ; p = . ). simultaneously, the patients showed erythrocytes hyperaggregation compared with control (;t , ;t ; :i . , :b). in the first group (crystalloids) described violations persisted throughout the study time. in group (crystalloids + hes), the deformability was higher than in the st group, from days till the end of the study, attaining the normal range, and also higher than in the third group (crystalloids + gelofusin). in the third group, deformability index was not significantly different from group . according aggregatometrical data in the first group hyperaggregation syndrome remained the entire period of observation. hes adding (group ) decelerated aggregate formation (:t , :t ; ;i . ). in contrast, modified gelatin adding enhanced erythrocyte aggregation (;t :i . , :b). conclusions. crystalloid solutions are not able to improve microrheological parameters. hes / . increases rbc's deformability and reduced rbc's aggregability. gelofusin increases erythrocyte aggregation and no effect on deformability. introduction. trauma patients often require norepinephrine (ne) infusion and fluid challenge to keep normal blood pressure values. the reliability of dynamic predictors of fluid responsiveness during vasopressors therapy is under debate. we investigated the impact of norepinephrine (ne) infusion changes on pulse pressure variation (ppv) assessed with the mostcare system (vytech health, laboratoires pharmaceutiques vygon, ecouen, france) in intensive care unit patients. this device is a pulse contour method that provides cardiac output and fluid responsiveness variables and does not need any kind of calibration or preloaded data. methods. trauma patients ( female, male, mean age ± ) admitted to a -bed university hospital medico-surgical icu were prospectively enrolled. inclusion criteria were: mechanically ventilated patients (tidal volume [ ml/kg and constant respiratory rate); invasive arterial blood pressure monitoring; ne infusion. ppv values were recorded continuously during three different haemodynamic states: at baseline (t ), min after a . lg/kg/min ne increase (t ), min after a further . lg/kg/min ne increase (t ), min following the reduction of ne to t dosage (t ) and min after setting ne to baseline value (t ). during the study neither fluid challenge nor other vasoactive/inotropic drug changes were done. anova test was applied. results. see data in table . at t ne mean dosage was . lg/kg/min (range . - . lg/kg/min). the mean ppv was: at t . ± . %, at t . ± . %, at t . ± . %, at t . ± . %, at t . ± . % (p \ . ). conclusions. our findings demonstrated that ppv was significantly affected by changes in ne: the higher the ne dosage the lower the ppv. changes in arterial tone due to ne infusion can impair ppv reliability in assessing fluid responsiveness in trauma patients. introduction. in mechanically ventilated patients respiratory variation in the arterial pulse pressure (dpp) is a reliable predictor of fluid responsiveness . respiratory variation of pulse oximetry plethysmographic waveforms correlate to dpp and can be calculated automatically in real time (heart-lung index [hli Ò ] from hamilton medical). this prospective study evaluates the relationship between dpp and hli Ò to predict fluid responsiveness. mechanically ventilated patients were investigated; all connected to an hamilton g ventilator and ventilated in adaptive support ventilation (asv), paralyzed and none had severe cardiac dysrhythmia. were eligible for fluid expansion. dpp, hli Ò (obtained from a finger probe pulse oxymeter integrated to the ventilator) and cardiac index (ci from transthoracic echo-doppler), were obtained before and after fluid expansion ( ml/kg of hea over min). ci-responders were defined by % increase from baseline. results. out of the patients were ci-responders and had significantly higher hli Ò before volume expansion ( % ± vs. % ± , p \ . ). before fluid expansion hli Ò was correlated with dpp (r = . , p \ . , fig. ). hli and dpp were significantly correlated with change in ic induced by fluid expansion (r = . and r = . , respectively). objectives. the primary end point of this study was to evaluate the rvd of the ivc in icu patients with spontaneous breathing. methods. icu patient with spontaneous breathing and signs of hypoperfusion (oliguria, mottles, serum lactate level [ mmol/l) were eligible after the approval of the local ethics committee. we excluded patients with acute heart failure with pulmonary edema, moribund and arrhythmic patients. the trans thoracic echocardiographic (tte) evaluation was done by confirmed intensivists (level [ in echocardiography). the aortic diameter measured at the lv outflow chamber and the tvi were measured. the vena cava inferior diameters at inspiration and at expiration were measured on the sub costal view. the rvd of the ivc was defined as the (maximal ivc diameter -minimal ivc diameter)/maximal ivc diameter. these measures were realized at t , before fluid challenge, and after a fluid challenge of ml of hes % ( . / ) over min (t ). patients with an increase of tvi of more than % were considered as responders to the fluid challenge. the measures of tvi and of the rvd of the ivc were validated by an experimented intensivist and echographist (level ) after blinding the patient' name and of the times of measurement. roc curves were constructed, and the cut off was determined as the closest point of the roc curve to the ideal point (sensibility = specificity = ). the values are expressed as median and extremes. objectives. our objective was to test whether non invasive assessment by trans thoracic echocardiography of sub aortic velocity time index (vti) variation after a low volume of fluid infusion ( ml of hydroxy ethyl starch, hes) can predict fluid responsiveness. methods. sub aortic vti was measured by transthoracic echocardiography before fluid infusion (baseline) in sedated patients with acute circulatory failure and low tidal volume mechanical ventilation in whom volume expansion was planned. then, vti was recorded after ml of fluid infusion over min, and after an additional infusion of ml of hes over min. we measured the variation of vti after ml of fluid (dvti ) for each patient. receiver operating characteristic (roc) curves were generated for dvti in all patients. when available, roc curves were also generated for pulse pressure variation (ppv) and central venous pressure (cvp). , volumes (gedvi) and variabilities (svv, ppv) have been suggested to predict volume responsiveness (vr). the final classification of a patient as ''volume responsive'' is usually made by a volume challenge (vc) with an infusion of a pre-defined amount of fluid over a certain time. among many variations of vcs, the infusion of ml crystalloid over min is one of the most established. despite superior predictive capabilities of svv, ppv and gedi compared to cvp and pawp in a number of studies, they fail to predict vr in a substantial number of patients. furthermore, the use of these parameters is limited due to femoral access of the cvc (gedi; cvp) or the absence of controlled ventilation and/or sinus rhythm (svv, ppv). repeated ''exploratory'' vcs with ml/kg might result in volume overload in some patients. objectives. therefore, we investigated the usefulness of a ''small vc'' with . ml/kg crystalloid over min compared to a standard vc with ml/kg over min. in patients equipped with picco hemodynamic monitoring we performed a min vc with ml/kg of crystalloid. during the vc transpulmonary thermodilution (td) was performed at , and min to obtain td-derived ci (ci td ). additionally pulse contour ci (ci pc ) was recorded in intervals of min. introduction. the prevalence of obesity, defined as a body mass index (bmi) c kg/ m , reaches epidemic proportions. it is not only a risk factor for health problems, but also exacerbates illness progression. consequently, the number of obese patients on the intensive care unit (icu) has increased enormously. caring for obese patients can be quite challenging due to the weight and size of this person. the extent of and specific problems associated to the care of obese icu patients are unknown. the aim of this study is to identify and quantify problems nurses face in caring for obese patients on the icu. this study was performed on the icu at the radboud university nijmegen medical centre and contained two parts. in the first part a selection was made of obese patients admitted between and ; these patients were matched with normal weight patients (bmi . - . kg/m ). patients were matched on gender, age, length of icu stay and apache-ii score. all patient files were screened for the presence and intensity of problems in caring for these patients. in the second part nurses were asked in a survey to share their experiences in caring for obese patients. they were asked about the nature, frequency and intensity of the problems they faced. in total, problems were identified in the screened patient files. seventy-two problems ( . %) occurred in care for obese patients and ( . %) in care for normal weight patients. in both groups, most of the problems were related to activities of daily living (adl) such as (re)positioning in bed, transfers and personal care. surprisingly, the intensity of the problems was similar in both groups. most of the problems were moderate (hardly to solve by one person) or severe (only to solve with two persons or special equipment). moderate problems occurred in . % of normal weight patients and in . % of obese patients; severe problems . and . %, respectively. this result was also confirmed by the survey. the nurses qualified most of the problems they were asked about as moderate or severe, and the frequency of the experienced problems was much higher. from the files it appeared that in . % of the obese patients nurses had adl problems. strikingly, in the survey nurses reported that they frequently ( . %) or even always ( . %) experienced adl problems in obese patients. nurses reported and experienced more problems in daily care for obese icu patients compared to normal weight icu patients. although the intensity of the problems with obese patients did not differ from normal weight patients, the frequency in which they occur was much higher. differences between reported problems and the survey suggest an underestimation of problems that can be solved by performing a prospective study. nevertheless, based on these results, and taking into account that obesity will increase in the future, we recommend anticipating to the needs of the nurses whenever possible. introduction. worldwide the number of obese patients (bmi [ ) is increasing rapidly ( ); this also includes patients admitted to the intensive care units (icu). this raises special demands on the staff, the surroundings and the equipment ( ) . often the obese patient is not mobilised according to the clinical standard this causes complications to breathing, circulation and skin etc. furthermore the length of stay in the icu increases and the mortality rises. objectives. the aim of this study therefore was to make clinical guidelines and recommendations for mobilisation of the obese icu patient based on evidence. this will increase the knowledge and importance of mobilisation between staff and on longer term improves the daily average number of mobilisations performed with these patients. a secondary aim is that increased knowledge on this topic will improve the interdisciplinary work between the different professions based on the same overall aim. a systematic review of the literature concerning mobilisation of the obese icu patients was made in the year - . the study is still work in progress analysing the literature to make guidelines and recommendations based on evidence. furthermore evidencebased education of special trained staff in mobilisation has been conducted in january/ february to improve their knowledge of the impacts mobilisation has on the respiration, circulation and skincare etc. the education was planned to aiming at a interdisciplinary audience. results. the preliminary results shows that it is more difficult to care for and mobilise the obese icu patient, because there is lack of space, non-availability of the correct equipment, too few available staff members and a significant negative attitudes among the staff towards the obese patient. recommendations are made within airway, breathing, circulation, nutrition, pain, equipment and patient experience according to the procedure of mobilisation of the obese icu patient. the recommendation was implemented in the already performed education and resulted in a changed attitude among the participant and improved the status of mobilisation in the daily prioritization. this knowledge was obtained in the evaluationinterview conducted approximately one month after the seminar. conclusions. according to the literature mobilisation of the obese icu patient needs special attention towards a safe clinical practise based on evidence with focus on both the patient and the staff. special attention towards this group of patient is created by performing evidence based research resulting in clinical guidelines that has to be implemented through theoretical and practical education on an interdisciplinary level. nurses are constantly exposed to the pain and suffering of those in their care . the primary aim of this study was to investigate the risk of secondary traumatic stress/compassion fatigue (sts/cf-the trauma suffered by the helping professional) and burnout (bo-emotional exhaustion, depersonalization, and reduced sense of personal accomplishment), and the potential for compassion satisfaction (cs-the fulfillment from helping others and positive collegial relationships) among nurses working in icu. an additional goal was to test the relationship of these three constructs to each other. ( ) . the use of closed suction circuits has been suggested beneficial as a prophylactic measure ( ) . objectives. the aim of this study was to compare the incidence of vap and the occurrence of desaturation during suction using either oss or css. we also investigated contamination of the closed suction circuit and the occurrence of adverse events. methods. css were a new product in our clinic. all staff underwent a user course supervised by the manufacturer of the closed circuit. after this, data were collected during four periods in , month css followed by months oss which was repeated twice. during the summer period css were used without any data collection and then followed by two periods of css and oss. all mechanical ventilated patients were consecutively included. a culture of deep endotracheal aspirate and a blind microbiology brush was taken in association with the intubation, after h and every monday. after changing css and in case of extubation, the tip of the catheter was sent for culture. demographic data were retrieved from the hospital database. data were analyzed with descriptive methods. results. the incidences of vap were higher in the css group (table ) . both suction systems showed almost no desaturation during and after suctioning. positive cultures were obtained in % of all the retrieved css catheters. the microbiological flora resembled the species found in the airway cultures. there were no inter patient contamination and neither did the bronchoscopy frequency differ between oss and css patients. in the css group six adverse events were seen; three tube occlusion and three incidences with secretion clogging. conclusions. the use of a css did not prevent vap, in our study. there were no benefit with css other than maybe to protect the staff and our finding of positive culture in % of the cases is in line with earlier studies. objectives. the aim of this study was to determine which intensive care patients the nurses defined as 'difficult' and their experiences in coping with such patients. the study was carried out as a qualitative design with voluntary nurses employed in five intensive care units of a research and training hospital. the data were collected using demographic characteristics form and a semi-structured interview form. interviews with nurses were made individually and face to face. the data were evaluated by using colaizzi's phenomenological data analysis method. as a result of data analysis into two categories and two themes were identified. the categories were ( ) difficult patient definition of the nurses, ( ) the effect of difficult patients on their care, and ( ) how the nurses are affected and cope with difficult patients. the nurses listed their reasons for defining some persons as difficult as difficult physical care of the patients, and the difficulty in communicating due to dementia, agitation, alzheimer's disease or the patient's personal characteristics. the nurses said that they found taking care of patients they found difficult physically and psychologically demanding. they used methods such as finding out the patient's problem and taking appropriate measures, increasing communication with the patient and providing explanations, trying to obtain spiritual satisfaction and transferring the patient's care to another nurse when communication problems were impossible to overcome. intensive care nurses have difficulty in caring for and communicating with some intensive care patients due to the characteristics of the disease, physical/psychological factors and personal characteristics. we found that nurses continued the care of these ''difficult'' patients by focusing on solving their problems, transferring the care to another nurse when necessary or by trying to obtain spiritual satisfaction. methods. teams of three delirium experts visited ten icu's in the the netherlands in which the cam-icu was incorporated in daily practice, twice. these teams consisted of two consultants in either psychiatry, clinical geriatrics or neurology, and either a research-physician (mmjve) or a research-nurse (mvdb). based on cognitive testing, inspection of the files and dsm-iv criteria for delirium, the teams classified patients as awake and not delirious, or delirious or comatose. this classification served as gold standard to which the cam-icu as performed by the bed-side nurses was compared. a simple table was used to calculate the sensitivity and specificity. results. delirium experts performed assessments. ( %) of these patients were assessable for delirium, ( %) patients were excluded because the level of consciousness was too low, and ( %) patients were non-assessable due to other reasons. overall, we found a sensitivity of % ( % ci - %) and a specificity of % ( % ci - %). the strengths of this study include the large numbers, the multicentre design, the extensive evaluations by teams of various delirium experts and the independent assessments of delirium experts and bed-side nurses. a limitations is the time interval between the expert assessment and the administration of the cam-icu (mean min; standard deviation min). there were striking differences in implementation strategies of the cam-icu between the centres. tables , . rd esicm annual congress -barcelona, spain - - october s introduction. presence of expiratory ineffective efforts in mechanically ventilated patients is a common problem associated with increased duration of mechanical ventilation, length of stay and also a higher cost and mortality. nowadays, identification and categorization of expiratory asynchronies can only be done at the bedside with the continuous observation of the ventilator interface. nurses must be skilled to understand non appropriate situations of anomalous patient-ventilator interactions. objectives. we tested the hypothesis that after specific training nurses would acquire enough skills to detect expiratory efforts as intensive care expert physicians would do. training phase: nurses were provided with selected bibliography on patient ventilator interaction and afterwards trained by intensivists with expertise on mechanical ventilation ( h/day during days) on airway pressure, flow and volume waveforms identification and eye interpretation of early and late ineffective expiratory efforts during expiration. validation phase: airflow and airway pressure waveforms were obtained from different icu mechanically ventilated patients using and acquisition and processing biomedical signal software (better care Ò ). one thousand and seven breaths were randomly selected from a total of , , breaths. subsequently, selected breaths were blindly analyzed by trained nurses and intensivists to identify ineffective expiratory efforts. introduction. several publications indicate that manual hyperinflation is a widely used measure in the icu, but more important is the fact that there is no uniformity in the implementation of this measure. this is also on my ward. in literature there are a number of reasons given to start manual hyperinflation: abolish mucus retension, improve oxygenation and removal of atelectasis. the positive effects are improved compliance, improved oxygenation and a decrease in the number of vap's (ventilator associated pneumonia). the negative effects are a decrease in cardiac output due to high peak pressures, an increased risk of baro-/volutrauma and the risk of giving too much tidal volumes. the risk of barotrauma increase with pressures above cmh o. other side effects include the development of a pneumothorax and increased icp (intra cranial pressure). objectives. creating more awareness of the procedure with lower peak pressures as a result. methods. through literature review, clinical courses and the introduction of a pressure gauge achieve greater uniformity and awareness of the procedure. we used a flow analyzer of imt medical, a laptop with flowlab software version . . and an artificial lung to demonstrate how much pressure and volume is generated during manual hyperinflation. conclusions. compliance with bts guidelines could be improved. unsurprisingly co-morbidities were frequent, but did not seem to affect outcome. use of a pneumonia severity assessment tool was sub-optimal, however mean curb- score didn't correlate with that recommended to prompt critical care assessment. apart from functional status, we are unable currently to identify any factors in this age group which can be used to guide critical care admission decision making. conclusions. in our study the incidence of complicated pneumonia was / , patients admitted in picu. in necrotizing pneumonias the blood cultures were more positive than in non-necrotizing patients. although the surgical approach in necrotizing pneumonia is controversial, it resulted in a insignificantly lower mortality rate, comparing with non-necrotizing pneumonias. background. community-acquired pneumonia (cap) of mixed etiology has frequently been described in the literature, but its clinical significance remains unknown. the aim of this study was to describe the prevalence, clinical characteristics, and outcome of severe cap of mixed etiology in icu patients. a -year prospective study was conducted on consecutive patients with severe cap admitted to icu in whom an extensive microbiological investigation was performed. results. patients were included. a single pathogen was detected in ( . %) cases, while two or more pathogens in ( . %) cases. the most frequent pathogens' combinations were those of two bacteria ( . %) and bacterium plus virus ( . %). compared with patients with monomicrobial pneumonia, patients with mixed pneumonia were older, had higher severity score (psi) and were more likely to have previous chronic pulmonary disease (see table below). moreover, mixed cap patients showed similar clinical and analytical data at admission but increases in the frequency of respiratory distress and in length of stay and a trend to higher orotracheal intubation and mortality rates. a mixed etiology was detected in % of cases with cap requiring icu hospitalization and was associated with older age and increased severity. despite similar radiological features (n of involved lobes, pleural effusion) at admission, cap with mixed etiology showed a trend to worse clinical course and outcomes than monomicrobial pneumonia. objectives. to assess the incidence and aetiology of pneumonia in a mixed medicalsurgical icu, in order to develop local epidemiologically guided protocols to reduce antibiotic resistance selection in patients with pneumonia. methods. retrospective observational study on prospectively collected data in a mixed medical-surgical icu of a secondary care italian hospital. at our institution, epidemiological data on infections and data on antibiotic use are recorded since ; in a new electronic recording of icu infections was introduced. type of infection, germ characteristics, clinician diagnosis and antibiotic use were prospectively collected in an electronic database and retrospectively reviewed. antibiotic exposure index was calculated as each antibiotic total amount administered divided by its defined daily dose times total days of admission. between and a total of patients were admitted to our icu. pneumonia was the commonest infectious disease at admission ( cases, % of patients), and the commonest infectious complication during icu stay ( new occurrences, % of total pneumonia patients). table shows major epidemiological findings in the study population. the incidence of acquired pneumonia was remarkable: . cases every , days of mechanical ventilation. the most frequent isolated organisms were s. aureus ( patients) and p. aeruginosa ( patients). methicillin-resistant s. aureus (mrsa) accounted for % of pneumonia caused by s. aureus, and its prevalence matched closely the exposure index to vancomycin. such a high incidence of mrsa is consistent with other records in mediterranean countries. carbapenem-resistant p. aeruginosa was somewhat less of a problem ( % of pneumonia by p. aeruginosa), and was not apparently associated with antibiotic exposure, at least within the unit. conclusions. in our retrospective observational study we found a high incidence of pneumonia at our institution, as well as a high percentage of mrsa, the latter with strong relationship with exposure to vancomycin. new protocols for infection containment and antibiotic usage are urgently needed. introduction. community-acquired pneumonia (cap) carries a high morbidity and mortality. a major problem is the insufficient monitoring of cap by standard chest radiography, as the evaluation depends highly on the observer and the extent of pulmonary infiltration cannot be assessed properly ( ). objectives. the aim of our study was to compare the process of inflammation in cap measured by alveolar nitric oxide (no)-analysis ( ) in exhaled breath and the extent of the inflammatory infiltration by electrical impedance tomography (eit) ( ) in spontaneously breathing patients. after approval of the local ethic committee and obtained written informed consent patients with cap were included in the study. all patients showed an acute pulmonary infiltration in chest x-ray, pulmonary symptoms (coughing, shortness of breath), positive findings in auscultation, leukocytosis, elevated crp and a pneumonia severity index c . no analyses (analyser cld sp, eco medics, dürnten, switzerland) were performed at t (up to h after admission), t ( days after admission) and t ( days after admission. eit measurements (eit evaluation kit, dräger medical, lübeck, germany) were performed at t and t and inhomogeneity of ventilation was assessed by offline analysis. all measurements were made at beside in sitting position. data were compared by t test and regression analysis. results. there was no significant correlation between the alveolar no concentration and the extent of inhomogeneity of the local infiltration measured by eit. also during the study the time course of the inhomogeneity index was not correlated with change in exhaled no. the right/left distribution of the pulmonary infiltration in the chest x-ray and the eit measurement showed a positive correlation (p \ . ; r = . ). conclusions. pulmonary regional infiltration in cap measured by eit can not predict the actual alveolar process of inflammation in the lung. nevertheless the monitoring devices give additional information to better evaluate the time course of inflammation and the dimension of the respiratory dysfunction in diseased lung. organizing pneumonia (op) presenting as acute respiratory failure (arf) is a relatively rare disease, and was only previously specifically reported in small series [ , ] , with mortality up to %. these studies were performed before the publication of international consensus classification of idiopathic interstitial pneumonias in [ ] . objectives. to compare clinical features and prognosis of patients with op with those of patients presenting diffuse alveolar damage (dad), during arf. design: retrospective monocentric study in a university hospital conducted during an yr-period. to determine predictors of niv failure in patients who were intubated for respiratory failure and extubated directly to niv. methods. this is a retrospective analysis of prospectively collected data from january to dec . patients with respiratory failure were mechanically ventilated in a university hospital's medical intensive care unit (icu) and subsequently extubated to niv. physiological and biochemical parameters, using arterial blood gas measurements, were collected at the end of the spontaneous breathing trial and h after the application of niv. failure of niv was defined as respiratory failure requiring re-intubation within h. out of patients, . % were successfully extubated to niv. success rates were . % in patients with chronic obstructive pulmonary disease (copd) and . % in other patients (p = . ). patients who failed niv were more tachypnoeic, acidaemic and hypercapnic pre-niv, and more tachycardic, hypotensive, acidaemic, hypercapnic and hypoxaemic post-niv (p all. ). on logistic regression analysis, three physiologic parameters predicted niv failure: pre-niv respiratory rate (or . , % ci . - . per breaths increase), post-niv heart rate (or . , % ci . - . per beats increase) and post-niv systolic blood pressure (or . , % ci . - . per mmhg decrease). conclusions. physiologic parameters, including the respiratory rate pre-niv, and heart rate and systolic blood pressure post-niv, independently predict niv failure post-extubation. these parameters should be taken into account in the decision to extubate directly to niv. introduction. discontinuation of mechanical ventilation in critically ill patients is a challenging task and involves a careful weighting of the benefits of early extubation and the risks of premature spontaneous breathing trial (sbt). only a few studies have explored indices derived from both heart rate and breathing pattern variability analysis for the estimation of weaning readiness. objectives. to investigate heart rate (hr) and respiratory rate (rr) complexity in patients with weaning failure or success, using both linear and nonlinear techniques from signal processing theory. methods. forty-two surgical patients were enrolled in the study. there were who passed and who failed a weaning trial. signals were analyzed for min during two phases: despite of passing the protocol the decision to extubate was postponed in some patients. to gain insight on the physicians reasons for continuing mechanical ventilation after passing the wean screen protocol. a wean screen protocol was introduced at a mixed medical (neuro-)surgical icu of a teaching hospital in december to april . ventilation practitioners assessed ventilated patients and recorded the physicians reasons for continuing mechanical ventilation despite of passing the wean screen protocol. . patients were ventilated in this period. daily screens were performed, screens were successful. only passed wean screens resulted in extubation. the rate of extubation was %. % screens did not lead to liberation from mechanical ventilation. the extubation rate does not correspond with the findings of the abc trial with an extubation rate of %. table shows the physicians' reasons to continuing mechanical ventilation. it should be noted that all patients with an unsafe airway were patients with a glasgow coma scale (gcs) of b [intracerebral haemorrhage ( %), cerebral infections ( %), post-cpr encephalopathy ( %) and severe brain injury ( %)]. we accomplished a reduction in the use of sedatives (- % midazolam and - % propofol) and morphine (- %) ( table ). the amount of time spend on ventilators decreased, albeit not significantly (p = . ). this was probably due to the vap-ventilatorbundle (introduced last year), the heterogeneity of our cohort and the already short mv-duration. . non-invasive ventilation (niv) has been utilized in selected patients with hypoxemic arf to avert endotracheal intubation, which is related to life-threatening complications. niv has been also proposed to facilitate weaning and extubation in patients with hypercapnic arf. so far, no controlled randomized study has investigated the potential role of niv in weaning patients with hypoxemic arf. objectives. we designed this pilot study to assess safety and feasibility of niv to wean hypoxemic arf patients. twenty mechanically ventilated patients with hypoxemic arf were randomized to receive early extubation followed by niv application via helmet (helmet group) or conventional weaning through the endotracheal tube (tube group). primary outcomes were the duration of invasive mechanical ventilation and the adherence to the study protocol. secondary outcomes were protocol failure (i.e. need for re-intubation), icu and hospital mortality, rate of tracheotomy, duration of continuous intravenous sedation, weaning time, and septic complications. table . weaning through helmet by niv application following early extubation was safe and feasible. overall the adherence to the study design was %. in addition, in the helmet group, there was a significant reduction in the rate of tracheotomy and a trend toward a lower rate of protocol failure, and fewer days on invasive ventilation. there was no difference with respect to days of continuous sedation, icu and hospital mortality, weaning time and septic complications. ( ) . delirium is a common occurence on the icu and is associated with increased length of stay (los) and poor outcomes ( ) . objectives. we developed a combined daily sedation hold, delirium management, and weaning (sdw) protocol and implemented this to reduce icu los and improve outcomes. methods. a sdw protocol was implemented in . we prospectively audited all patients from january to march . delirium was measured using the icdsc. data was analysed using graphpad statistical software. results. consecutive patients were analysed. the incidence of delirium was % ( pts). of these, % ( ) had risk factors for delirium. there was no difference in onset of delirium between sexes, age, type of admission, or severity of illness. however, in patients with delirium, duration of mechanical ventilation (mv) and icu los were significantly longer and there was a trend towards increased hospital los ( conclusions. measuring the linear dependence of variables through time by k and ø may be used to determine non-linear behavior between the variables of the emmv. non-linear behavior during weaning perhaps indicates the dependency of, either the resistance or compliance of the respiratory system, on the ventilatory support (i.e. pi). accordingly, k and ø, estimated at the frequency interval form to (h) - , can provide information concerning to the dynamics of the respiratory system that can be used as a complement to determine the suitability of the mv withdrawal. objectives. to study the potential superiority of aprv on cmv in a subgroup of patients with severe ards. methods. retrospective observational study on patients severe ards who were admitted between july and january to mafraq hospital icu in uae. the diagnosis of ards was based on presence of bilateral infiltrates in cxr and p/f ratio of less than in absence of evidence of elevated left atrial pressure. all patients were managed according to ardsnet guidelines using low tidal volume cmv and iv steroids. criteria for transition to airway pressure release ventilation (aprv) included failure to wean down fio below % after h, hemodynamic instability due to high peep, and failure to maintain plateau airway pressure below cmh o. initial settings of aprv were ph , pl , th , and tl . with titration of fio as required keeping pao more than mmhg. we compared the outcome of cmv and aprv groups with special concern to the duration of mechanical ventilation, requirement for tracheostomy, and survival to icu discharge. twenty four male and females were included in the study with a mean age of years (± ). fourteen out of them fulfilled the criteria and were shifted to aprv within h of initiating mechanical ventilation. ten out of ( %) patients in the aprv arm survived to icu discharge versus out of ( %) patients in cmv group (p . ). survivors in aprv group spent significantly shorter periods of mechanical ventilation compared to survivors in cmv group ( . vs. . days p . ). while out of ( %) survivors in cmv required tracheostomy for prolonged intubation or recurrent lavage, only out of ( %) survivors in aprv group required tracheostomy tube placement (p . ). we concluded that aprv can be effectively used as rescue measure of ventilation in patients with severe ards. although our study does not show any mortality benefit of using aprv over cmv, there was a shorter ventilation days and icu stay using aprv. we strongly recommend further studies to investigate the probability of using aprv as initial mode of ventilation in this subset of patients. weaning from mechanical ventilation is a common daily procedure when caring for critically ill patients, and a lifesaving practice on which nurses are taking an increasing role with the introduction of nurse-led protocols. the literature supports that nurse-led protocols facilitate weaning and increase nurses' input in decision-making. on the other hand, decision-making is a complex function affected by the nature of the task, the decision environment and the characteristics of the decision maker. although the cognitive process of clinical decision-making has been investigated with many different methodologies, little is known about the decision environment and its impact on decisions' during the weaning process. objectives. this paper aims to address one of the factors of the clinical environment and its impact on the decisions when discontinuing mechanical ventilation. methods. this paper is part of a large comparative ethnographic study looking at nurses' input during the weaning process of mechanically ventilated patients. participant observation of critical care nurses took place in an -bedded icu in greece and an -bedded icu in scotland for months each to examine nurses' involvement in the decisions made. in-depth semi-structured interviews with the nurses followed focusing on how nurses perceived their participation in the decisions made. data from field notes and interview transcripts were analysed thematically using the qualitative data analysis software nvivo, version . inter-personal and inter-professional relationships were considered revealing influences of nurses' input in decision-making. clinicians' personality played a significant role in their involvement in decisions, whereas trust and appreciation, the sense of support and the sense of accountability were also considerable dynamics of inter-professional relationships and predisposed decision-making. clinical decision-making is a multi-dynamic process specifically in complex clinical long-term situations such as weaning. aspects of the decision environment, such as the interprofessional relationships should be acknowledged when introducing methods to enhance nurses' role in teamwork and collaborative decision-making in order to improve the weaning process of ventilated patients and their outcome. objectives. the objective of our study was to analyze the temporal trends and outcomes of two cohorts of patients ventilated with psv and pav+. a cohort of consecutive patients who were ventilated with pav+ and another cohort of consecutive patients who were ventilated with psv were compared. all patients had the same inclusion criteria (gas exchange, ventilatory mechanics, peep level, resolution/stabilization of the cause leading to invasive mv and appropriate level of consciousness). both modes were adjusted to predefined clinical criteria (psv to reach a respiratory rate about bpm and pav+ to reach a physiological inspiratory effort introduction. presence of expiratory asynchronies (ea) (ineffective efforts, cough and continued contraction of inspiratory muscles) is a common problem associated with increased duration of mechanical ventilation, longer stay, higher costs and increased mortality. because of the lack of systems that automatically detect and report ea, their identification is currently done by examining ventilator interface at the bedside or by applying dedicated algorithms in investigational conditions. validate the accuracy of linear mathematical algorithms to automatically detect ea built in a new computerized system that grabs and process data from different bedside icu monitors and mechanical ventilators. observational and prospective study in a general icu of beds. two beds were equipped with a software (better care Ò ), a technological platform responsible for data acquisition and synchronization, processing, storing-as non static and processable dicom objects-and also for integrating all this data with health information systems. by using the better care Ò platform, a total of , , breaths from consecutive adult patients were collected with at least h of mechanical ventilation. algorithm # : the ea algorithm consisted in a mathematical analysis of the airflow and airway pressure waveform variations during expiration not followed by a mechanical breath. algorithm # : designed to select , breaths out of the total number. this algorithm sorted and classified the breaths by the percentage of deviation from the expected expiratory curve. the result was , breaths covering most of the shapes the expiratory curve could have. five expert attendant physicians independently analyzed the , selected breaths and classified them as ea or not. the ea algorithm processed the same , selected breaths and assigned a percentage to each one, according to the variation in the shape and direction of the expiratory airflow and airway pressure curves. the expert criterion against the ea algorithm scores was used to construct a logistic regression model. we calculated sensitivity, specificity, positive predictive value and negative predictive value. the predictive performance of ea algorithm was evaluated using roc curves. optimal sensitivity and specificity were achieved by setting the cut-off point at a ea algorithm score of %. a variation in the shape and direction of the expiratory airflow and airway pressure curves [ % compared to the theoretical curve identified an ea with a sensitivity of . %, specificity of . %, a positive predictive power of . % and a negative predictive power of . %. introduction. near-infrared spectroscopy (nirs) in combination with a vascular occlusion test (vot) has been proposed to assess and identify metabolic and microcirculatory alterations during sepsis and shock in critically ill patients. however, to automatize repeated measurements at the bedside, this technique can potentially cause discomfort to the patient. vascular arterial occlusion performed in the finger may be a more attractive method to execute repeated measurements at the bedside because of more tolerability from the patient. we have previously showed in healthy volunteers that nirs can be used on finger to assess the sto response to vot and that min was an adequate occlusion time to provide the best curve fit for nirs dynamic variables . objectives. we aimed to investigate whether sto response to vot obtained from the finger could predict conventional sto response measurements obtained from the thenar of critically ill patients. parameters of sto response were measured with an inspectra spectrometer model (hutchinson technology inc.) equipped with a -mm or a -mm probe. the mm probe was placed over the thenar eminence and the -mm probe was place over the ventral face of the middle finger. we performed in each patient a series of two vascular occlusion tests (vot): one on the finger ( min) followed by one on the arm ( min). the measurements were obtained within h of intensive care admission and every h thereafter until day . vot-derived sto traces were analyzed for baseline, ischemic (rdecsto , %/min) and reperfusion (rincsto , %/s) parameters. we performed paired of nirs measurements in critically ill patients (age ± ; m/ f). although sto did not differ significantly between thenar and finger ( % ± vs. % ± ; p = . ), rincsto and rdecsto were statistically lower in the finger ( . %/s ± . vs. . %/s ± . , p = . ; . %/min ± . vs. %/min ± . ; p = . ). we performed bivariate linear model with correlated errors in which sto outcomes on thenar and on finger were treated as responses. the correlation was significant for sto and rincsto , but not for rdecsto (table ) . furthermore, mixed model analysis showed that thenar-sto as dependent variable could be significantly predicted by finger-sto parameters with estimation coefficient (± se) of . ± . (p = . ), . ± . (p = . ) and . ± . (p = . ) for sto , rincsto and rdecsto , respectively. correlation of sto response: finger vs. thenar a prospective randomized clinical trial performed in icu's of an university and teaching hospital during a . year period, involving septic and non-septic patients, randomized (after stratification) to hemodynamic monitoring, by picco tm or pac with both techniques allowing cardiac output and central/mixed venous o saturation monitoring. methods. hemodynamic management was guided by extravascular lung water index (evlwi) and global end-diastolic volume index (gedvi) in the picco tm group and by the pulmonary capillary wedge pressure (pcwp) in the pac group for consecutive days. primary outcome measures were ventilator-free days (vfd), for which the study was powered, and lengths of stay in icu and hospital. secondary measures were the course of cardiorespiratory parameters, fluid and vasopressor requirements, lactate levels, organ functions and mortality. in the study period, septic and non-septic patients were included. patients received a picco tm and a pac catheter. monitoring arms were comparable at baseline, although sepsis differed from non-sepsis in hemodynamics and severity of lung injury. premorbidity was greater in non-septic patients. the fluid infusions and balances did not differ between monitoring arms, except at t = h when the picco tm group had a more positive balance (p = . ). cardiac index and central venous o saturation increased more in the course of time in the picco tm than in the pac group. the decrease in norepinephrine requirements strongly tended to favor the picco tm group (p = . ). the course of lactate levels and organ failure did not differ between monitoring arms. vfd did not differ among monitoring arms. picco tm monitoring was associated with relatively fewer mechanical ventilation and icu days in sepsis but more in non-sepsis (after day ). the changes in respiratory parameters, sofa and number of catheter-related complications did not differ among the arms of the study. overall, patients ( %) died in the picco tm group before day and ( %) in the pac group (p = . ). conclusion. hemodynamic management guided by picco tm monitoring is safe and results in better tissue oxygenation than guidance by pac, without inducing pulmonary overhydration, in septic and non-septic, critically ill patients. this was associated with fewer mechanical ventilation and icu days in patients with sepsis but more days in patients with non-sepsis (after day ), partly attributable to greater cardiovascular premorbidity in the latter. the major primary and secondary endpoints, vfd and mortality, were not affected. introduction. non-invasive evaluation of endothelial function may be easily accomplished by ultrasound assessment of flow-mediated vasodilation (fmd) of the brachial artery, but this technique has not been fully explored in septic patients. objectives. this prospective study aims to investigate the role o fmd analysis on intra hospital prognosis of patients with severe sepsis and septic shock. adult patients admitted to the intensive care unit with a diagnosis of severe sepsis or septic shock (\ h of duration) were consecutively included. fmd of the brachial artery was measured upon admission and after and h using a high-frequency linear transducer ( . - mhz) according to internationally accepted protocols. a group of apparently health subjects paired for gender and age was used as controls for fmd analysis. patients were followed up to discharge or death. we studied adult patients mean age ± years, females, % on vasopressors with sepsis predominantly of abdominal or respiratory etiology ( %). apache ii risk score was ± and intra hospital mortality rate was %. fmd was similar in patients with or without use of vasopressors at baseline (p = . ). fmd in septic patients was significantly lower than in health controls ( . ± vs. ± %; p \ . ). we observed that survivors depicted a gradual improvement on endothelial function, so that h after sepsis onset fmd was significantly lower in nonsurvivors (- . ± vs. . ± %; p \ . ; time-group interaction p value = . ). conclusions. brachial fmd is altered in septic patients with hemodynamic instability and its improvement may be an early marker of favorable prognosis. introduction. change in pulse pressure variation (dpp) and respiratory variation of the pulse oxymetry plethysmogram (pop) may predict the hemodynamic effect of peep in mechanically ventilated patients [ , ] . reported comparisons [ , ] between pop variations (popv) and co or dpp are based on selection of - consecutive breaths (dpp b) during a ''stable'' period of pop. recently, a fully automatic ventilation mode (intellivent Ò , hamilton medical, switzerland) that incorporates an automatic and continuous popv calculation (hli Ò ) using a dedicated algorithm has been developed. the present study was designed to compare dpp b, dpp calculated with the algorithm as hli Ò (dppalg) and hli Ò. . . sedated icu patients ventilated with hamilton medical s ventilator (with integrated pulse oxymetry (po)) were included (age = ± years, saps ii = ± , no arrhythmia, norepinephrine: . ± . mg/h in patients, map = ± mmhg, vt = . ± . ml/kg). waveforms of po from a finger sensor and of blood pressure from a radial catheter were recorded for - h. from the waveforms, breath by breath (using respiratory flow signal), without pre-selection of stable periods and using known formula [ ] dpp b (averaging breaths without any filtering), dppalg and hli Ò were automatically obtained (matlab Ò ). dpp b was compared to dppalg ( pairs) using mann-whitney t test. pairs of hli Ò and dppalg values (see fig. below) were compared using linear regression and bland-altman method. a dppalg threshold value of % was used to generate hli Ò roc curves. results. dpp b and dppalg were significantly correlated (r = . , p \ . ), but standard deviation of dpp b were higher than the standard deviation of dppalg ( . ± . vs. . ± . %, p \ . ). dppalg and hli Ò were correlated (r = . , p \ . ), mean difference was ± %. hli Ò above % predicted dppalg above % with a sensitivity of % and specificity of % (roc: . ). conclusions. dpp b should be interpreted with caution due to the high variance of this index. in real conditions and during long time monitoring dppalg and hli Ò are in acceptable agreement and hli Ò may help estimating continuously the hemodynamic effects of ventilation. introduction. transthoracic echocardiography (tte) is supposed not to be useful in ventilated patients (pt). echocardiography is usually performed transesophageally in ventilated pt and is thought to be independent of the examiner's skills. we want to demonstrate that tte in ventilated pt could be learned even by medical students with reasonable results and that tte could add useful informations for interpretation of the hemodynamic status. objectives. in a prospective observational study consecutive patients (pt) were enrolled in a -bed medical intensive care unit of a university hospital. inclusion criteria was septic shock according to actual guidelines. transthoracic echocardiography (acuson cv , siemens, germany) was performed by a medical student in each subject on day , day and survival was reported on day . tte-examination was reduced to an apical -chamber view for interpretation of left ventricular global function and calculation of left ventricular ejection fraction (ef) with the simpson method and to a subcostal view in order to examine the diameter of the inferior caval vein (ivc) and to rule out pericardial effusion. each examination was digitally recorded and was interpreted by an experienced cardiologist. every single pt was mechanically ventilated. cardiac output (co) was measured with the transpulmonary thermodilutional technique (picco-catheter, pulsion, germany). the insertion of the picco-catheter took place due to an individual physician's decision. crp was measured as an parameter of inflammation. results. pt, mean age years ± . , male ( %), pt with known coronary artery disease ( %), pt with known dilated cardiomyopathy ( %). mean apache ii-score . ± . . pt died within days ( %). picco-catheter was inserted in pt ( %). tte could be successfully performed in pt ( %). the following values are expressed as mean values ± sd, student's t test, p \ . denotes statistic significance. ef on day . % ± . , ef on day . % ± . , p = . . ivc on day . mm ± . , ivc on day . mm ± . , p = ns. co on day . l/min ± . , co on day . l/min ± . , p = . . crp on day . mg/dl ± . , crp on day . mg/dl±, p\ . . pericardial effusion in no pt. in older pt coronary artery disease is common and ef is at the start of septic shock severely diminished. ef decreased slightly in the early course of septic shock, may be as an expression of septic cardiomyopathy. the ivc diameter did not change and may not be useful as a predictor of preload in ventilated pt. co decreased over time as the hyperdynamic circulation in septic shock is getting normalised. tte adds useful hemodynamic information and should be performed in each ventilated pt. tte could be performed in almost each ventilated pt and is easily learned even by medical students. ( , ) , which can often be caused by anaemia. in current guidelines the transfusion trigger is haemoglobin (hb) \ g/dl, but there is no recommendation for scvo ( ). objectives. the aim of this retrospective study was to evaluate the change in scvo before and after transfusion and to reveal whether co -gap reflects it. methods. over a month period hb, scvo , co -gap and o -extraction ratio (o er) were recorded before and after transfusion. data are presented as median [interquartile range], for statistical analysis wilcoxon, mann-whitney tests and pearson correlation were used as appropriate. results. out of transfusion events the scvo was measured in cases. after transfusion hb increased significantly: . [ . - . ]- . [ . - . ] g/dl, p \ . . the median scvo was %, therefore two groups were created: ''low'' (scvo \ %, n = ); ''high'' (scvo c %; n = ). hb increased significantly in both groups (p \ . ), but scvo conclusions. in the high-group the low hb levels did not cause oxygen debt, as after transfusion hb increased significantly but scvo did not, and o er and co -gap were within the normal range. our results give further support that not only the hb level should serve as a transfusion trigger, but measures of oxygen debt such as scvo and co -gap should also be considered, hence unnecessary transfusions could be avoided. introduction. intellivent Ò is a fully closed loop ventilation designed to keep the patient within target ranges of etco and spo . the system includes an automatic adjustment of peep and fio following the ardsnetwork tables [ ] . if required peep is changed by cmh o every min with a maximal possible value set by the user or depending on an automatic and continuous calculation of the respiratory variations of the plethysmogram from an integrated pulse oxymeter (hli Ò ), i.e. the higher the hli Ò the lower the maximal peep allowed by the system. the present study was designed to estimate whether changes in peep are reflected in hli Ò changes. in sedated icu patients ventilated for min in fully closed loop ventilation with intellivent Ò (hamilton medical s ventilator), episodes of significant changes in peep (c cmh o) were selected and hli Ò values within min before and after peep changes were collected. statistics were done using sigmastats with p \ . as significant. results. changes in peep and in hli Ò are shown in the table ± cmh o ± cmh o ± % ± % p \ . the correlation between change in peep and change in hli Ò is shown on the fig. . conclusions. based on these preliminary data changes in peep are reflected hli Ò changes and may help estimating continuously the hemodynamic effects of ventilation. objectives. we have tested a axis accelerometer sensor for detection of regional left ventricular ischemia. in pigs a -axis accelerometer was sutured to the left ventricular (lv) apical region in left descending coronary artery (lad) supply area accelerometer x-axis measured longitudinal-, y-axis circumferential-and z-axis radial epicardial motions. epicardial displacements were calculated from the acceleration signals and systolic displacements within ms after peak r on ecg was measured. lad was occluded for s to induce regional lv dysfunction. myocardial circumferential strain (shortening) measured by echocardiography in the lv apical anterior region was used to confirm ischemia. the ecg st-segment in lead ii was also monitored. data are presented as mean ± se. early systolic displacement at baseline was ± mm, ± mm and ± in circumferential, longitudinal and radial directions, respectively. lad occlusion induced akinesia in circumferential ( ± mm, p \ . ) and radial ( ± mm, p = . ) directions, whereas longitudinal displacement changed less to ± mm (p = . ). ischemia was confirmed by echocardiography strain, showing lengthening in systole (p \ . ). no significant changes were observer in the ecg st-segment during coronary occlusion (p = . ). introduction. there is increasing evidence to suggest perioperative complications are predictive of long term survival and that reducing them may improve survival rates . goal directed therapy has been shown to reduce mortality and morbidity perioperatively, with those unable to increase oxygen delivery perioperatively having demonstrably worse outcomes. the advent of non invasive tissue oxygenation monitors using near infrared spectroscopy has allowed further study of oxygen flux during goal directed therapy. objectives. to observe changes in tissue oxygenation during an h oxygen delivery targeted post surgical optimisation program and provide long term mortality followup of a surgical cohort of high risk patients. methods. patients undergoing high risk surgery and postoperative optimisation (targeting of oxygen delivery index of [ ml/min/m ) on the tensive care unit at a london teaching hospital were enrolled. each patient underwent a protocolised haemodynamic optimisation protocol as per our standard unit policy for h with consecutive recordings of tissue oxygenation at the thenar eminence using an inspectra monitor. additional variables relating to global and tissue perfusion were measured concurrently. patients were followed up for survival status at . years using routinely available information held within our hospital records. in hospital mortality was . % (n = ), whilst at . years this had increased to % (n = ). there was no significant difference between apii scores ( ) versus . ( ), age . ± . versus . ± . or operation type for survivors and non-survivors at . years respectively. significant differences between groups were found however for admission and mid optimisation protocol ( h) hr and sto (see table there were no significant differences in measured variables for day mortality. conclusions. there appears to be a statistical and clinical difference in hr and tissue oxygenation between the long term survivors of high risk surgery who undergo monitored postoperative goal directed optimisation. introduction. bronchoscopic bronchoalveolar lavage (b-bal) is today the gold standard for sampling of inflammatory markers in the distal airways. nonbronchoscopic bronchoalveolar lavage (n-bal) by ordinary suction catheter has been investigated as a more easily accessible method for alveolar sampling in the setting of acute respiratory distress syndrome (ards). the results, however, were disappointing, probably due to more proximal sampling by the n-bal. to investigate wether n-bal by a catheter with physical properties similar to those of the bronchoscope is comparable to b-bal. methods. b-bal and n-bal by cook's airway exchange catheter was performed with ml normal saline on opposite sides min apart at nine different occasions on anesthetized and intubated pigs. the volume of the recovered lavage was noted, after which the fluid was analyzed for albumin, total cell count, viability and differential cell count. statistical analysis was performed using wilcoxon's rank-sum test. results. n-bal yielded significantly higher albumin content than b-bal ( . ± . vs. . ± . mg/l, p = . ). in all other measurements there were no significant differences between n-bal and b-bal (recovered volume . objectives. we hypothesized that collagen synthesis and degradation are disturbed in acute respiratory failure. in the finnali-study we defined acute respiratory failure as need of noninvasive and/or invasive ventilatory support for more than h ( ). after informed consent we collected blood samples for serum procollagen propeptides i and iii (pinp, piiinp) and ictp levels at study admission, day , and . patients with all four blood samples were included in this substudy. multiple organ dysfunction (mod) was defined as two or more individual organ sofa scores of - at any day during the first week. results. the study population comprised of finnali patients ( ). the mean (sd, range) age was years ( , - ) and the majority were male %. on admission the mean sapsii score was ( , - ). patients ( %) developed mod during the first days. over time piiinp/pinp-ratio first increased and then decreased to baseline by day while pinp/ictp-ratio decreased and then decreased to baseline by day (p \ . and p = . , respectively) ( fig. ). there were no statistical differences in the ratios between patients with or without mod. conclusions. we found that in patients with acute respiratory failure the balance of collagen synthesis was towards degradation of type i collagen and production of collagen type iii. ± ng/ml in the ards group, and significantly higher than the . ± . ng/ml in the ali (not ards) group. the difference in hmgb values in the early stage between the group that died up to the by th day and the surviving group was not significant, but the hmgb values were significantly higher in the group that died until the th day and th day than in the survival group. it was concluded that differences in hmgb values in the early stage after the onset of ali (not ards)/ards are useful as outcome determining factors after days of onset. an inverse correlation was observed between the hmgb values and lung oxygenation, suggesting the possibility that hmbg is involved in the development of respiratory failure. s. shibata , g. takahashi , n. shioya , s. endo akita city hospital, anesthesiology, akita, japan, iwate medical university, emergency medicine, morioka, japan, iwate medical university, critical care medicine, morioka, japan sivelestat sodium hydrate (sivelestat) is a selective polymorphonuclear leukocyte elastase (pmn-e) inhibitor and has also been shown to be effective for pulmonary disorders associated with sirs in clinical patients. blood levels of inflammatory cytokines have been shown to be decreased in patients treated with sivelestat. however, since patients with sirs have already received other drugs, it remains indefinite whether or not sivelestat might suppress the production of cytokines. moreover, it is difficult to clarify any cells releasing cytokines. in the experiment using cells isolated from the blood, intercellular mutual actions and cytokine networks were blocked and the experiment failed to faithfully reproduce the in-vivo condition. objectives. the possibility of sivelestat suppressing the production of cytokines from granulocytes and monocytes was assessed by intracellular cytokine staining using the whole blood culture method and flow cytometry to faithfully reproduce the in-vivo condition. methods. blood samples were collected from healthy volunteers. a vehicle (control group), lipopolysaccharide (lps; lps group), or lps + sivelestat (sivelestat group) was added to the whole blood, followed by the addition of a protein transport inhibitor in each group. after incubation, they were subjected to staining of the cytokines retained in the cells by the addition of an anti-interleukin (il- ) or anti-tumor necrosis factor a (tnf-a) antibody and analysis by flow cytometry. the data were analyzed by the kolmogorov-smirnov test. values obtained [d/s(n)] result from the comparison of the fluorescence histograms of each sample with a control one. addition of sivelestat at low concentrations ( and lg/ml) significantly (p \ . ) suppressed the production of il- from granulocytes induced by a low concentration ( ng/ml) of lps. on the other hand, the granulocytic production of tnf-a induced by a high concentration of lps ( ng/ml) was significantly (p \ . ) suppressed by treatment with sivelestat at high concentrations ( and lg/ml). with regard to the monocytic production of tnf-a and il- induced by lps, there was no significant suppression of either tnf-a or il- production by sivelestat. conclusions. sivelestat, a neutrophil elastase inhibitor, suppressed granulocytic production of il- and tnf-a, suggesting the potential usefulness of sivelestat for the treatment of various morbid conditions involving il- and tnf-a in their onset. introduction. coagulation, fibrinolysis and extravascular fibrin deposition are the hallmarks of the pathogenesis of acute lung injury (ali). pai- has a central role in antagonizing fibrinolysis by decreasing the plasminogen turnover to plasmin. pai- has been suggested as a clinical severity marker of ali. in previous studies it was associated with higher mortality and morbidity in the critically ill. upar is a cell surface receptor activating the serine protease upa. increased expression of upar is found in various stages, including inflammation, tissue remodelling and malignancies, indicating poor prognosis. pai- antagonizes the proteolytic activities of upa and plasmin. objectives. we sought to evaluate the prognostic value of supar and pai- for -day mortality of patients with acute respiratory failure (arf). the finnali-study patients needed invasive or non-invasive ventilation for more than h ( ). blood samples were collected from patients at baseline and on day after baseline. healthy volunteers were also analyzed. sera were frozen at - °c until analyses. concentrations of supar and pai- in blood serum were measured by enzyme linked immunosorbent assay (elisa). data are presented as median (iqr). the prognostic value of supar and pai- for -day mortality was determined with roc analysis. in the critically ill, supar and pai- were . ( . - . ) ng/ml and . introduction. acute lung injury is a common disease in intensive care, associated to various septic or inflammatory diseases. inflammation is part of the defense mechanisms of innate immunity, occurring after tissue injury. objectives. the aim of the project was to decipher the transcriptional changes occurring after the onset of an inflammatory injury by intravenous injection of oleic acid. experimental study of the lung transcriptome after oleic acid injection. thirtysix c bl/ j mice, aged of weeks, were sacrificed at h, h , h, h, h and h after physiological serum or oleic acid injection ( ll) in the caudal vein. left and right lung were separated for mrna extraction and pathological examination. labelled cdna were hybridized on cdna nylon microarray (tagc, marseilles, france) and raw data were extracted from scanned images with bzscan software. raw data were normalized with the quantile method, and supervised analysis was conducted with significance analysis of microarray algorithm within the r statistical suite and bioconductor libraries. after the administration of oleic acid, the mice were tachypneic and prostrated. all survived during the first hours. the pathological analysis of lung tissue revealed an early inflitration of the lung tissue by polynuclear cells, as well as a pulmonary edema. these alterations were not observed after h. the time course analysis of transcriptional lung data identified a thousand genes which expression is modulated after injury. hierarchical clustering identified major groups of genes. the first one ( genes) is composed of genes transiently up-regulated between h and h after oleic acid injection. th second group ( genes) is composed of genes expressed between h and h. the third group ( genes) is composed of genes expressed at the later time points ( h- h). the functional annotation linked these signatures with keywords related to pro-inflammatory response, vascular endothelium modification and lipid metabolism, respectively. rt-pcr analysis of pro-(tnf, il ) and anti-inflammatory (il , il ) markers related the pro-inflammatory phase to the earlier time points ( h- h ) and the anti-inflammatory phase to the late points (after h). conclusions. oleic acid injection in mice induced a transient acute lung injury. this is confirmed by clinical, pathological and transcriptional modifications. the modulation of gene expression after the oleic acid injection revealed an early pro-inflammatory response, followed by an anti-inflammatory response and lipid metabolism modificiations. this model could now be used to describe the specific modulation occuring during pulmonary infection and critical injuries like acute respiratory distress syndrome. introduction. ventilator associated lung injury (vali) is influenced by tidal volumes, airway pressure and cyclic opening of alveoli during mechanical ventilation. preserved spontaneous breathing during partial ventilatory support may be protective, but it is not known whether the transpulmonary pressure generated by spontaneous breathing has the same effect on vali as if generated by the ventilator. to determine whether hemodynamics, respirtory function and vali are influenced by the amount of support provided by pressure support ventilation. after approval from the institutional animal care committee, acute lung injury was induced in anesthetized sd rats by acid aspiration. ten animals each were then ventilated with positive end-expiratory pressure cmh o in pressure control (pc), pressureregulated assist control (ac) or pressure support mode with % (ps ), % (ps ) or % (ps ) pressure support of initial distending pressure needed to maintain tidal volume. pc animals were paralyzed. after h animals were killed and vali determined. results. there were no differences in baseline characteristics. acute lung injury was characterized by a decrease of the p/f ratio from ± to ± mmhg and of the dynamic compliance from . ± . to . ± . ml/cmh o. conclusions. compared to controlled ventilation, preserved spontaneous breathing activity improved hemodynamic stability, respiratory function and lung edema clearance. the reduction in pressure support did not lead to reduced tidal volume, but transpulmonary pressure was preserved by muscular activity of the chest wall. no difference was observed between full or % of pressure support, but further reduction in pressure support resulted in increased wet-dry ratio. objectives. we studied the effects of metabolic acidosis on enzymatic and non-enzymatic no-production in hypoxic and hyperoxic lung regions in a pig model. eighteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (lll) and hyperoxic gas to the rest of the lung. six pigs received hcl infusion (hcl group), six pigs received n w -nitro-l-arginine methyl ester (l-name) and hcl (l-name + hcl group) and six pigs received buffered ringer's solution (control group). no concentration in exhaled air (eno), no synthase (nos) activity in lung tissue, and regional pulmonary blood flow were measured. results. metabolic acidosis, induced by infusion of hcl, decreased the relative perfusion to the hypoxic lll (q lll /q t ) from (± ) to (± )% in the hcl group (p \ . ), and from (± ) to (± )% in the l-name + hcl group (p \ . ), without any measurable significant changes in eno from hypoxic or hyperoxic lung regions there were no significant differences between the hcl and control groups for ca + -dependent or ca + -independent nos activity in hypoxic or hyperoxic lung regions. metabolic acidosis augmented the hypoxic pulmonary vasoconstriction, without any changes in pulmonary enzymatic or non-enzymatic no-production. when acidosis was induced during ongoing nos-blockade, the perfusion of hypoxic lung regions was almost abolished, indicating acidosis-induced pulmonary vasoconstriction was not no dependent. assessing and monitoring biomarkers in acute lung injury (ali) may improve knowledge of its pathogenesis, early recognition, and management and predict remote organ injury and multiple organ failure. objectives. early consents for research are difficult to obtain in patients with or at risk of ali because of the emotional burden of the severity and sudden onset of the disease. however, study samples may be obtained from left-over clinical blood draws, which are readily available if processed adequately. the aim of this study was to compare fresh and ''waste'' blood samples prospectively in a series of consecutive critically ill patients. the hypothesis is that ''waste'' blood samples if appropriately processed provides accurate and reliable results comparable to the gold-standard, which is immediate collection and processing of fresh blood samples. prospective study comparing biomarkers of epithelial injury (srage) and inflammation ( different cytokines/chemokines) in critically ill patients measured on fresh blood or waste blood, kept at degrees celsius for h. an automated system performed a daily screening of adults in the icu with an increased risk for ali (lung injury prediction score, lips) within h of admission and/or on recognition of the diagnosis of ali, using the american-european consensus conference criteria. risks factors for ali include pneumonia, sepsis, pancreatitis, shock, aspiration, high risk surgery and high risk trauma. irb approved the protocol and written consent was obtained from patients or their surrogates. statistical measurements were performed using the bland-altman analysis for correlation between fresh and waste blood sample data. between may and december , patients were enrolled. one patient was excluded due to lack of sample. samples were obtained either at one time point (n = ) or two, on consecutive days (n = ). female/male patient ratio was / . seven of the patients had ali. twenty two patients had risk for ali with a median lips score of (iqr . - . ). sepsis was the most common risk factor, present in patients. in-hospital mortality was % ( / ). the bland-altman plot (mean bias ± se, limits of agreement) showed good correlation for il- ra (- ± . pg/ml, - . to . pg/ml), il- ( . ± . pg/ml, - to . pg/ml), il- (- . ± . pg/ml, - . to . pg/ml), il- (p ) (- . ± . pg/ml, - . to . pg/ml), mcp- (- . ± pg/ml, - . to . pg/ml) and srage (- ± pg/ ml, - to pg/ml) between fresh blood and ''waste'' blood samples. in patients with ali, properly stored blood, drawn for clinical purposes, can be processed within h for research purposes. however, the stability of each biomarker of interest needs to be individually validated before using stored blood introduction. pulmonary surfactant inactivation following acute lung injury might promote alveolar derecruitment and reduce the airspace available for ventilation, making the lung more prone to ventilation-induced lung injury (vili). our aim was to test the potential for a protective effect of exogenous surfactant treatment in a model of acid aspiration and vili. methods. male c /bl mice were anesthetized, mechanically ventilated (vt ml/ kg; rr /min; peep ± . cmh o; fio . ) and immediately subjected to intrabronchial (right) instillation of . ml/kg hcl . m. mechanical ventilation went on for min. min after the acid instillation, mice were treated with exogenous surfactant ( mg of phospholipids/ml) given as bolus of ml/kg in the right bronchus (surf group). we measured oxygenation, lung compliance (measured every min throughout the experiment), macrophage inflammatory protein (mip) in broncho-alveolar lavage (bal) fluid. . pao at the end of the experiment was significantly higher in the surf than in control group ( ± vs. ± mmhg, p \ . ). although surfactant bolus caused a reduction in lung compliance measured and min after treatment, in the surf group compliance restored to ± % of the post injury level, while it decreased in control group to ± % (p \ . ). there were no differences between groups in the dosage of mip- in bal neither in right or left lung. conclusions. exogenous surfactant treatment improved lung function in a murine model of two hit lung injury. grant acknowledgment. introduction. ventilator induced lung injury significantly contributes to the mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury. understanding the molecular basis for response to cyclic stretch and its derangement during high volume ventilation is of high priority. objectives. to identify specific molecular regulators involved in the development of ventilator induced lung injury. we undertook a comparative examination of cis-regulatory sequences involved in the coordinated expression of cyclic stretch responsive genes using microarray analysis. analysis of stretched vs. non-stretched cells identified significant enrichment for genes containing binding sites for the transcription factor atf (activating transcription factor ). to determine the role of atf in vivo, we compared the response of atf gene deficient mice to wild type litter mates in an in vivo model of ventilator induced lung injury. results. atf deficiency results in increased sensitivity to mechanical ventilation alone or in conjunction with inhaled lipopolysaccharide ( mg/kg) as determined by assessment of lung and bronchoalveolar lavage cell infiltration and pro-inflammatory mediator release, pulmonary edema and indices of tissue injury. the expression of genes containing an atf cis-regulatory region was significantly altered in gene deficient animals. atf protein expression and nuclear translocation is increased after mechanical ventilation. conclusions. atf deficiency confers increased sensitivity to mechanical ventilation alone or in combination with inhaled endotoxin. in our model, atf acts to ''counterbalance'' cyclic stretch and high volume-induced inflammation, limiting its potential to cause additional lung injury and consequently protecting animals from injurious cyclic stretch. objectives. our aim was to evaluate the role of the alveolar macrophages in a murine model of ali, by selective depletion of this type of cells from the air space achieved by clodronate administration. mice were treated (it) with ll of clodronate (clo)-or pbs (pbs)-liposomes. after h mice were anesthetized and ventilated (vt - ml/kg, rr min - , fio . ); in order to induce lung injury ml/kg of hcl ( . m) or air bolus (sham group) was instilled in the right bronchus. mice were ventilated for min, and extubated after awakening. h after injury, animals were sacrificed and broncho-alveolar lavage (bal) and blood gas analysis (fio = . ) were performed. . h after lung injury animals with alveolar macrophages depletion, showed a better oxygenation versus pbs-treated group. however, recruitment of neutrophils in bal was not statistically different between clo_hcl and pbs_hcl group. results. high levels of oc were found in patients treated by mg of ot bid. oc levels ranged from , to , ng/ml in these patients. concentrations of oc were five-to tenfold higher than concentrations reported in healthy volunteers. lesser levels were found in patients treated by mg of ot bid. nevertheless, the patient with the moderate renal failure seemed to accumulate oc (levels ranged from to ng/ml) whereas concentrations reported in the patient with a normal renal clearance were below ( - ng/ml). conclusions. ecmo seemed not to have any influence on oc concentrations while renal insufficiency seemed to be the parameter leading to oc accumulation. as ic was very low and reached even with usual dosage, increasing ot dose to mg bid appeared to be unnecessary. objectives. aim of our study was to evaluate the effect of nursing care on patients undergoing venous-venous ecmo for acute respiratory distress syndrome (ards). methods. we recorded physiological and ecmo parameters (heart rate, arterial blood pressure, mixed venous saturation (svo ), arterial oxygen saturation (spo ), body temperature and extracorporeal blood flow (bf)) before and during daily nursing in patients undergoing vv-ecmo for several days (each patient was followed on average for . days, cases in total). arterial blood gases were also collected before and after nursing care. daily nursing was performed following defined steps (sponge bath, oral hygiene, change position of endotracheal tube, elevation with scooping stretcher for sheets replacement and back hygiene, dressing replacement) in agreement with a standard protocol in use in our department. (expressed as mean ± standard deviation). all patients were affected by ards h n -related. patients were sedated with propofol ( ± mg/h) or midazolam ( . ± . mg/h) plus an opioid drug (fentanyl ± mcg/h or remifentanil . ± . mcg/kg/min or sufentanil . ± . mcg/kg/min). ramsey score before nursing was . ± . . in cases patients were paralysed. in table we summarized the adverse events observed during nursing care, divided into hypertensive or tachycardic episodes, blood oxygen desaturation, reduction in svo or reduction in bf. forty-nine sedative bolus were administered during nursing (mean request for each patient: . ± . ), always after an episode of hypertension or tachycardia (most frequently during elevation with scooping stretcher and changing position of endotracheal tube). although in cases preventive bolus of sedation were administered before nursing, in of those cases ( %), additional bolus were required. we found an inverse correlation between bf and the increase in heart rate, drop in arterial saturation and svo . despite active warming, we observed a drop of . ± . °c (p \ . ) in body temperature. nursing care may have a significant impact on physiologic parameters of patients during vv-ecmo. tachycardia, hypertension and reduction in oxygenation were commonly recorded and were not prevented by pre-nursing bolus of sedation but were attenuated in patients with higher bf. introduction. prone position has been used in cases of ards with refractory hypoxemia but some physiological effects are still unknown. prone position could increase intraabdominal pressure (iap) and could lead to acute renal failure (arf). acute kidney injury in icu is associated with increased mortality. objectives. the aim of this study was to determine whether prone position could increase intraabdominal pressure and possibly promote arf. we studied all adult ards patients who were ventilated using the protective strategy defined by ards network criteria and who needed prone position to improve oxygenation. we collected respiratory data (ventilator parameters and gas exchange) and hemodynamic variables (heart rate, systolic, diastolic and mean arterial pressure). iap was measured using the abdo-pressure tm bladder transducer following world society of acute compartment syndrome recommendations. abdominal perfusion pressure was calculated as mean arterial pressure minus iap. main renal parameters were: filtration gradient (fg), creatinine clearance, fractional excretion of sodium (fena) and urea (feurea). patients were classified according to rifle score after each manoeuvre. all data were recorded in prone and in supine position at least once per day. results. the study included patients ( male) admitted to a medical-surgical icu over a one-year period. their mean age was . ± . and length of icu stay was ± days. all patients had primary ards and had received nephrotoxics. icu mortality reached %. we recorded at least manoeuvres per patient (a, b, c). prone positioning improved pafio ratio from . ± to ± (p = . ). iap showed a small increase from . ± . to . ± . mmhg (a; p = . ), from . ± . to . ± . mmhg (b; p = . ) and from . ± . to . ± . mmhg (c; p = . ). there were no statistically significant changes in hemodynamic parameters or abdominal perfusion pressure. renal function parameters (fg, creatinine clearance, fena and feurea) showed no modification after each prone positioning. in contrast, when patients were classified according to rifle score, we observed a trend towards worsening, though this was not statistically significant. conclusions. prone positioning improved arterial oxygenation in primary ards patients and was associated with an increase in iap. however, creatinine clearance and glomerular filtration remained unchanged. percutaneous extracorporeal life support system (p-ecls) including ecmo becomes widely used in medical and surgical emergent situation, such as refractory cardiogenic shock, cardiac arrest and acute respiratory failure. patients requires highly specialized intensive care and monitoring system. we reviewed our ecls experience and tried to analyze the clinical outcomes, factors for survival and frequently faced problems during management for improving weaning and survival rate (medical vs. surgical patients). introduction. in spite of the huge efforts spent over the last years, conventional treatment of acute hypoxemic respiratory failure (ahrf) is often inadequate and alternative procedures must be instituted. icus skillful in extracorporeal membrane oxygenation (ecmo), as recently shown [ ] , may improve survival of these patients. since we developed a treatment algorithm for ahrf which encomprises: ( ) low flow venous-venous ecmo (lf-ecmo) consisting in a relatively low initial blood flow (bf, - . l/min) to maximize extracorporeal co removal while providing partial oxygenation (if needed, bf can be increased up to . - l/min to keep arterial po above mmhg); ( ) femoral-femoral percutaneous cannulation with - fr cannulas to allow free movements of the neck and increase patient's tolerance; ( ) early institution of spontaneous assisted ventilation (sb) and weaning from sedation and mechanical ventilation (mv) while on ecmo. objectives. to review our last years lf-ecmo activity. methods. study period was january - . lf-ecmo entry criteria were: potentially reversible acute hypoxemic respiratory failure, lis c , no evidence of intracranial bleeding and no absolute contra-indications to heparinization. ecmo was performed with different type of heparin coated hollow-fiber artificial lungs. . we treated patients (mean ± sd, ± . years old, % males, bmi ± , sofa . ± , oi ± ). % of these patients were placed on ecmo at other hospitals and transported to our icu by a dedicated ecmo team. ventilation days before ecmo were ± (range - ). before ecmo vt/kg was ± . and rr was ± : after ecmo beginning vt/kg was unchanged while rr decreased to ± (p\ . ). ecmo was set at bf . ± l/min, gf . ± . l/min, fio . ± . introduction. ventilating patients with acute lung injury (ali) in supine position potentially leads to an impaired pulmonary gas exchange. prone position (pp) is an attractive means to improve ventilation-perfusion (v/q) ratio [ , ] but has several contraindications and showed no improvement in survival so far [ ] . another therapeutical option is an upright position, which is easy to perform and has theoretical advantages over pp: the upward shift of the abdominal compartment is less pronounced, thus increasing thoracoabdominal compliance [ ] . however, to date regimes of an upright position did not tilt patients more than ° [ ] . objectives. we hypothesised that a °standing position (sp) during mechanical ventilation may improve respiratory function. furthermore, we aimed to determine the feasibility of a sp for h during mechanical ventilation. we studied adult patients, receiving mechanical ventilation for more than h in the intensive care unit of an university hospital. after recording baseline data, patients were placed in a °sp with the body entirely straight. further data sets were recorded during h in sp, and after patients position was readjusted to supine position. functional residual capacity (frc) increased immediately after reaching sp (p \ . ) and remained elevated after repositioning to supine position. pao /fio ratio and compliance decreased initially during sp, but increased (p \ . ) after patients were retransferred to supine position. haemodynamic variables remained stable under a moderate increase of doses of catecholamines during the study period. conclusions. changes in respiratory function during sp are probably explained by a downward shift of the diaphragm due to gravitational forces leading to an increased frc but not altering v/q ratio as demonstrated by the pao /fio ratio. after reaching the initial supine position the opening of the lung proved by the elevated frc is the predominant effect now associated with an increase in oxygenation as reflected by the pao /fio ratio due to an optimised v/q ratio. our results are confirmed in a subgroup analysis for patients meeting ali criteria. ventilating patients in sp may be a new therapeutical approach to improve respiratory function in patients with ali. ( ) . there are several clinical trials investigating the efficacy of the free radical scavenger n-acetylcysteine (nac) in ards, but its advantage remains uncertain. objectives. critically appraise and summarize all randomized clinical trials involving intravenous nac administration in adult patients suffering from ards. we included trials involving participants with ards according to the american-european consensus conference criteria ( ) regardless of the underlying cause, and where one of the groups was treated with intravenous n-acetylcysteine in bolus intravenous doses or as continuous infusion, or combination of the two, and the other group was given placebo or standard treatment. conclusions. the main finding of this meta-analysis is that intravenous nac is ineffective in reducing mortality, length of stay or duration of mechanical ventilation in ards. we also found that late administration of nac may be associated with adverse outcome. the mechanism of this potentially deleterious effect remains unclear, but dosing and timing of nac appear to be critical issues. objective. to evaluate if extubation during ecls is harmful or beneficial. a -year-old woman was admitted to our intensive care unit (icu) after removal of a left ventricular assist device. this device was implanted as bridge to recovery for postpartum cardiomyopathy and ventricular function seemed to have recovered sufficiently. however, shortly after icu admittance she developed massive left and right ventricular failure. therefore a centrally cannulated veno-arterial ecls (maquet permanent life support) was implanted as a bridge to transplant. four days later she was extubated while on full ecls support, in order to reduce the risk of ventilator associated pneumonia. while on ecls, the patient was mobilized, practiced with an ergometer and chatted with her family. three days later the patient underwent cardiac transplantation. the postoperative period was characterized by temporary pulmonary failure, due to the combination of lung edema and atelectasis. eventually she made a full recovery. discussion. ecls provides a valuable means as bridge to transplantation, bridge to bridge or bridge to recovery. with the increasing use of ecls for circulatory failure, debate about the necessity of mechanical ventilation during this treatment ensues. ecls is usually applied under deep sedation and controlled mechanical ventilation. discontinuation of sedation possibly prevents intensive care acquired weakness. extubation during ecls may provide better pulmonary perfusion due to negative intra-thoracic pressure. furthermore, the awake and extubated patient is able to mobilize and exercise which may reduce the risk of atelectasis and ventilator associated pneumonia. our patient however developed pulmonary edema and atelectasis after discontinuation of ecls. the edema was probably a consequence of reperfusion injury, due to severely decreased pulmonary flow while on ecls. an absent ventilatory drive while on ecls may have led to hypoventilation while the patient was extubated, resulting in atelectasis. an extensive medline search resulted in one other case report describing an extubated patient on ecls. intermittent non-invasive positive pressure ventilation was used to prevent atelectasis, but the patient developed pneumonia after days of ecls. our patient was successfully extubated while on ecls. however, we conclude that there is insufficient evidence to recommend or oppose extubation of patients on ecls for circulatory failure. severe ards and refractory hypoxemia were defined with a pao / fraction of inspired oxygen (fio ) ratio of b , or uncompensated hypercapnea with a ph of \ . despite receiving optimal conventional treatment. the ecmo can be used as a rescue treatment in these case. objectives. evaluation of severe ards treated with extracorporeal oxygenation (ecmo). all these ards were due to bacterial pneumonia or h n influenza. over the last year (december -january ), the recourse to extracorporeal oxygenation (ecmo) was used in ten patients with severe ards and severe hypoxemia. two groups were defined: bacterial pneumonia with ards (bp group, n = ), and h n influenza with ards (h n group, n = ). all ecmos were implanted at the bedside to facilitate intra-hospital or inter-hospital transfer, because of severe hypoxemia or hemodynamic instability making impossible patient mobilization before ecmo. results. data sets of patients of consecutive patients treated with ecmo were complete and included into analyses. we had no clinical or radiological evidence for thrombosis or clotting within ecmo-circuit with a target-ptt of s. one patient with systemic aspergillosis died because of intracranial hemorrhage. one ecmo circuit had to be replaced due to insufficient oxygenator function after days. further data are presented in tables and . conclusions. in this retrospective analysis of patients who underwent ecmotreatment, ac with low-dose heparin (target-ptt of s) was safe and without any observation of macroscopic thrombosis or clotting within the circuit. transfusion requirements and intracranial hemorrhage were low as compared with previous reports [ , ] . therefore our data suggest that it is possible and safe using ecmo-therapy with low-dose heparin. introduction. in response to h n pandemy, italy and lombardy created a national and a regional icu network, respectively, for treatment of ards patients. our hospital policlinico san matteo of pavia participated with a team for inter-hospital ecmo implantation and subsequent patient transport. objectives. description of the pavia ecmo team and activity analysis. methods. our team is composed by a cardiac surgeon, two intensivists, a perfusionist, an icu nurse, two emergency rescue technicians and a driver. all necessary aids for implantation and intensive care are ranged in three trolleys and three transport bags. equipments are firmly mounted on a two-level steel bridge connected to a spinal board. a portable ultrasonograph is also available. the ecmo team was alerted by the national call center. each mission used two ambulances, and in one case the ambulances were embarked on a hercules c j. from october to december , four patients were implanted and transported, three suffering from h n influenza (including a -kg body weight patient) and one from acute mitral valve rupture. all patients, already mechanically ventilated with maximal support, had veno-venous ecmo implanted by femoro-femoral percutaneous cannulation. the median mission duration was of . h (range - h). all patients were transported to our icu, where the median ecmo duration was of days (range - days). no major managing issue occurred during the ecmo missions, and patient hospital survival was of %. a multispecialist team with good knowledge of ecmo can provide an effective support in severe respiratory failure, with ecmo implantation in peripheral hospitals and subsequent patient transport, thus realizing a fast and safe continuum between phone call activation and admittance to the reference center. introduction. when patients with sever respiratory failure are treated with v-v ecmo the right heart sometimes fails. this is a serious complication with a high mortality. in our unit these patients have been converted to v-a ecmo, although it is not fully agreed upon in the ecmo community due to previously depressing results. objectives. to evaluate the results of conversion to v-a from v-v ecmo in case of right heart failure. retrospective analyses of all patients with severe respiratory failure, treated between and at the karolinska ecmo centre. patients who were converted to v-a ecmo due to right ventricular failure were evaluated. a total of patients ( adults, peadiatric, neonatal) were treated on v-v ecmo for severe respiratory failure. of them ( adults, peadiatric, neonatal) needed conversion to v-a ecmo due to right ventricular heart failure demonstrated clinically by multiorgan failure and verified by echo cardiography. the survival after conversion to v-a ecmo was / ( %) in the adult age group, / ( %) in the peadiatric age group and / ( %) among the neonates. conclusions. given the high risk of fatality if not treated, conversion to v-a from v-v ecmo should be considered when the right ventricle fails. patients on v-v ecmo with right ventricle heart failure have very bad prognosis. it is concluded from the present results that conversion to v-a ecmo can save some of these patients. cardiac surgery and regional hemodynamics: objectives. to test whether tapse and right ventricular systolic (sm) and diastolic (em and am) tissue doppler imaging velocities are related with pulmonary artery systolic pressure (pasp) and length of the weaning process in mechanically ventilated patients with acute heart failure (ahf). methods. rv fractional area change (rvfac), left ventricular ejection fraction (lvef), pasp, tapse, sm, em, am rv tdi velocities, early diastolic mitral e wave and e maximal tdi velocities of the mitral annulus at the lateral wall were obtained at admission by doppler echocardiography in a cohort of patients with ahf, presented with pulmonary oedema, who required positive-pressure ventilation for more than h in the intensive care unit (icu). echo-derived measures were compared between patients with and without pulmonary hypertension, whereas their association with duration of mechanical ventilation and length of the weaning process was tested with multivariate linear and logistic regression analysis. and increased e/e ratio ( . ± . vs. . ± . , p \ . ) compared with subjects with normal pasp (n = ). these variables were negatively associated with duration of mechanical ventilation (r = . , beta slope = - . for tapse, r = . , beta = - . for sm, r = . , beta = - . for em/am, p \ . ) and were proven to successfully discriminate patients with (n = ) and without (n = ) prolonged weaning ([ days of weaning after the first spontaneous breathing trial failure, p \ . for all comparisons). conclusions. we suggest that in critically ill patients with ahf presented with pulmonary oedema, low tapse and rv tdi velocities upon admission are associated with pulmonary hypertension and prolonged length of the weaning process. objectives. the aim of the study was to study changes in cerebral blood flow (cbf), as determined by tcd, during the early postoperative course of cvs and to correlate such changes with post-operative nc. we studied patients undergoing extracorporeal circulation cvs (coronary by-pass, valve replacement or both) between march and march . cbf was assessed by measuring bilateral mca flow velocities by tcd before and , and h after cvs. changes c % between consecutive tcd results were considered significant. demographic and clinical variables, co morbidities, euroscore, sofa, type and duration of surgery and type and severity of nc were also recorded. patients were assigned to groups according to cbf changes from baseline: a) changes b %; b) cbf increases c %, c) cbf decreases c %. nc were classified as major (stroke, tia and coma) and minor (delirium, encephalopathy, transient cognitive impairment). we used descriptive statistics and inference by v , anova and pearson's correlation. of the patients, were excluded ( early post-operative death and due to technical difficulties or incomplete tcd recordings). of evaluable patients, ( %) had no cbf changes (group a), ( %) had increases c % (group b) and ( %) had decreases c % after cvs (group c). a positive correlation was found between cbf changes and duration of circulatory arrest (p \ . ), maximum sofa score (p \ . ), respiratory dysfunction (p \ . ) and duration of mechanical ventilation (p \ . ). neurological complications occurred in patients ( %), of which ( %) were major and were minor ( % introduction. the sole monitoring of macrohemodynamic variables is not always sufficient in the early detection of tissue hypoperfusion, especially in cardiac surgical patients that frequently present with microcirculatory derangements. near infrared spectroscopy (nirs) is an easily applicable non invasive technique that has been used to provide an estimate of tissue oxygenation at the bed side. objective. the aim of our study was to evaluate the effect on outcome of guiding hemodynamic therapy and specifically inotrope titration in cardiac surgical patients postoperatively with nirs. methods. patients operated on with cardiopulmonary bypass were assigned, after stratified randomization (gender, euroscore-cutoff of ), to an intervention (ig) and a control group (cg). postoperatively, following cardiac intensive care (cicu) admission, after initial resuscitation according to cicu protocol, sto (%) was measured in patients of the ig in muscle sites: thenar, masseter and deltoid. if it was less than % in / sites, dobutamine was administered in incremental doses ( . lg/kg/min), with the sto (%) measured every half hour. the interventional period began upon cicu admission and lasted for h, after which both groups were treated according to cicu protocol. primary outcome measured was the oxygen consumption rate at the end of the h intervention period as assessed with nirs vascular occlusion technique. . patients were included in the study ( in the intervention group and in the control group). the groups did not differ statistically significantly regarding age, euroscore, and macrohemodynamic variables postoperatively (with the exception of cvp). microcirculatory parameters upon admission to the cicu also did not differ, excluding masseter sto (%). the oxygen consumption rate and the reperfusion rate increased in the h study period in both groups, without differing statistically significantly between the groups at any time point (cg oxygen consumption rate . ± . upon cicu admission and . ± . h later, ig . ± . and . ± . respectively) (cg reperfusion rate ± upon cicu admission and ± h later and ig ± and ± respectively). as far as outcome parameters were concerned, the groups did not differ statistically significantly in the total hours and total dose of vasopressors ± inotropes received, in the hours of mechanical ventilation, in the duration of cicu or hospital stay, and in sofa scores the days following the operation. conclusion. nirs guided titration of inotropes did not lead to a greater improvement in the microcirculation h postoperatively, or to a better outcome. the limited power of the study prevents definite conclusions on the role of nirs in hemodynamic therapy in cardiac surgery patients. objectives. to estimate the prevalence of pulmonary embolism among mv patients in icu and its association to deep vein thrombosis (dvt). in a monocentric prospective observational study, we included all the patients requiring mechanical ventilation with no previously diagnosed pe, who underwent a thoracoabdominal ct contrast scanner for any medical reason. we used a modified protocol for pe diagnosis with a -multidetector row ct scan read by two independent radiologists. the association with a dvt was explored by performing venous compression ultrasound of four limbs. objectives. the aim of this animal study was to evaluate the effect of intraabdominal hypertension on left ventricular diastolic function. after approval by an institutional animal care committee, rabbits were anesthetised before mechanical ventilation. an intraperitoneal infusion of . % glycine solution was used to increase intraabdominal pressure to mmhg. the right common carotid artery was catheterised in the neck in order to introduce a millar mikro-tip catheter (millar instruments inc., houston, usa) into the left ventricle. heart rate, arterial pressure, central venous pressure, oesophageal pressure and intraabdominal pressure were measured. the s time constant of relaxation which is considered as best index of relaxation was calculated using the derivative method ( ). all haemodynamic measurements were registered at baseline and after inducing intraabdominal hypertension. data are presented as mean (iqr) and were compared using a wilcoxon rank sum test. results. heart rate (from ± to ± beat/min, p = . ), mean arterial pressure (from ± to ± mmhg, p = . ) and dp/dt max (from , ± to , ± mmhg/s, p = . ) were not significantly modified by intraabdominal hypertension. however, the s time constant of relaxation increased significantly (from ± to ± ms; p = . ). conclusions. in this animal model, intraabdominal hypertension impairs left ventricular relaxation. these changes in the condition of the microcirculation have been related to the degree of organ dysfunction and thus patient outcome ie hospital length of stay. near infrared spectroscopy (nirs) is an easily applicable non invasive technique that has been used to provide an estimate of tissue oxygenation at the bed side. objectives. the aim of our observational study was to examine whether impaired tissue oxygenation as assessed with nirs immediately postoperatively correlates with hospital length of stay. patients undergoing a planned cardiac surgical procedure on cpb were included in the study. patients' thenar tissue oxygenation (sto %) was assessed with nirs postoperatively in the cardiac intensive care unit (cicu). results. patients undergoing cardiac surgery on cpb ( male/ female) (age: ± years, euroscore: . ± ; mean ± sd) were enrolled in the study. patients length of stay was . ( - ); median(range). the haemodynamic parameters of our patients upon admission to the cicu were: map ± mmhg, cvp ± mmhg, pcwp ± mmhg, mpap ± mmhg, ci . ± . l/min/m , svr ± dyne x s/ cm , pvr ± dyne x s/cm , hr ± bpm, hb . ± . g/dl, lactate . ± . mg/dl; (all variables expressed as mean ± sd). upon admission to the cicu all patients were mechanical ventilated, under vasopressor ± inotrope support and their central temperature was . ± . ; mean ± sd. the thenar sto % was ± ; mean ± sd. thenar sto % correlated statistically significantly with hospital length of stay (r = . , p = . ). discussion. tissue oxygenation as assessed with nirs reflects the balance between regional oxygen delivery in relation to oxygen utilization. an elevated sto in the presence of normal macrohemodynamics may reflect impaired oxygen consumption and thus an impaired microcirculation. conclusion. patients with impaired tissue oxygenation immediately postoperatively have a longer hospital length of stay. further studies are needed to confirm these results and to investigate the potential benefit from incorporating this information regarding tissue oxygenation in the treatment algorithm. objectives. the goal of this study was to compare two different sedative agents for implantation of crt-ds related to incidence of adverse events and patient's satisfaction. methods. the study included forty-two, asa iii-iv patients, undergoing transvenous implantation of crt-ds under local infiltrative anesthesia with to ml of % lidocaine. intraoperative sedation was established with intermittent boluses of midazolam ( - mg) to achieve desirable level of sedation. before the induction of ventricular fibrillation in order to test the defibrillator function of the crt-d device, patients received an additional bolus of either propofol ( . - . mg kg - , p group, n = ) or etomidate ( . - . mg . kg - , e group, n = ) targeting bis values in the range - . the incidence of apnea, hypotension, nausea, myoclonus, pain at injection site, allergic reactions as well as patient's satisfaction with anesthesia described as feel of well being were registered and compared between groups. results. in subjects ( %) no complications were recorded. myoclonus was registered in patients from e group ( %) and in none from p group (p \ . ). no patients receiving etomidate reported pain at injection site compared to patients ( %) receiving propofol (p \ . ). there was no significant difference in incidence of apnea between two groups ( vs. %, p = . ). two patients in p group ( %) and in e group ( . %) became hypotensive after delivering the hypnotic agent (p = . ). also, there was no statistically significant difference between groups considering the frequency of nausea ( % vs. %, p = . ). all the patients whom propofol had been delivered ( %) reported feel of well being and only four of them filed the same after etomidate ( %) (p \ . ). no allergic reactions and major adverse events were registered. conclusions. implantation of crt-ds and its testing can be successfully performed with administration of both propofol and etomidate as a safe procedure with low per operative morbidity and shorter complication rates. still, treating with propofol tends to be more satisfactory for the patients. introduction. ultra-short-acting b selective adrenergic antagonists are now widely used to control tachycardia and tachyarrhythmia perioperatively. among them, landiolol, a new ultra-short-acting b -blocker, has been reported to exert a more potent negative chronotropic effect with little effect on blood pressure than esmolol ( ). however, detailed mechanisms underlying different cardiovascular actions are still unknown. objectives. in this study we evaluated direct effects of landiolol on cardiac performance and single cell electrophysiology in comparison to those of esmolol. methods. the present study composed of two parts. the first part of the study used isolated guinea-pig hearts which were perfused in the langendorff mode at constant flow with oxygenated tyrode solution at °c. the coronary perfusion pressure (cpp) was continuously monitored throughout the experiment, and intrinsic heart rate (hr) and isovolumetric left ventricular contraction were measured with a thin saline-filled balloon inserted into the left ventricle. the second part of the study was to measure action potentials and ionic currents in ventricular myocytes isolated enzymatically from guinea-pig hearts. comparison of data was conducted by repeated-measure anova with post hoc test (bonferroni's correction). conclusions. esmolol had a more potent negative inotropic effect than landiolol. this effect is, at least in part, derived from shortening of apd. in addition, increase of the coronary resistance would facilitate the negative chronotropic action of esmolol in vivo. conclusions. nma moderates hpv in the conscious spontaneously breathing beagle, but not to the same degree as acz. as compared to acz, the additional methyl-group in nma may impair its capability in vivo to act on a non-ca acz-sensitive cellular receptor or channel or that both, ca-dependent and ca-independent actions of acz yield a greater effect. introduction. tee with bubble test is considered as the ''gold standard'' method to detect a pfo with right to left shunt. tcd is a non-invasive method which has been shown to be as accurate as tee for pfo detection. we conducted a multicenter trial to estimate the prevalence of pfo, the influence of the size of the heart chambers on the prevalence of pfo and the accuracy of tcd as a non invasive method for pfo detection in mechanically ventilated icu patients. one hundred icu patients ( m and f) under mechanical ventilation who needed a tee study for hemodynamic assessment were included in the study. in each patient, the presence of a pfo was detected by tee and tcd. three bubble tests with agitated haemacel Ò were performed by each method, with tee probe at and rotation and with tcd the gate of pulse wave doppler (pwd) at the m segment of the middle cerebral artery (mca). patients without temporal acoustic window to perform tcd were excluded from the study. the size of pfo was classified as grade i, ii and iii according to the number of microbubbles passing from the right to the left atrium and the number of hits (high intensity transient signals) detected with pwd in the mca (grade i: \ microbubbles or hits, grage ii: [ and \ and grade iii: more than microbubbles or hits). for each patient included in the study we measured and correlated the presence of pfo with the tidal volume (v t ), the plateau pressure (p plat ), the compliance of the respiratory system (c rs ) and the size of the right (rv) and left (lv) ventricle. results. mean p a o /fio was (min , max ), mean c rs was ml/cmh o (min , max ), mean v t was ml (min , max ) and mean p plat was cmh o (min , max ). the prevalence of pfo detected with tee was % and with tcd %. there was no pfo detected with tee and missed by tcd. tcd was more sensitive than tee in detecting pfo of grade i ( with tee, with tcd) and ii ( with tee, with tcd), while for grade iii the two techniques had equal sensitivity ( with tee, with tcd). no correlation was found between p plat , c rs , v t and the presence of pfo. on the contrary, a strong correlation was found between rv dilatation and the presence of pfo (p \ . ). conclusions. the prevalence of pfo detected by tcd is very high in mechanically ventilated icu patients and this may have important clinical implications. tcd is more sensitive than tee in detecting a small pfo. the presence of rv dilatation increases the prevalence of pfo. objectives. the aim of our study was to identify in mechanically ventilated patients for ali/ards the prevalence of pfo and to evaluate the factors that may influence the prevalence of pfo. methods. two groups of mv patients, one with ali/ards and one without respiratory failure (rf), were enrolled in the study. all patients underwent a tee study for hemodynamic assessment. in each patient three consecutive bubble tests with agitated haemacel Ò were performed at and rotation of the tee probe. the bubble test was performed through a central line in the inferior or superior vena cava (ivc, svc). a pfo was diagnosed by the presence of microbubbles in the left atrium within five cardiac cycles following the injection. furthermore, in ali/ards patients in whom a pfo was not detected at baseline mv, three consecutive bubble tests during recruitment maneuver at cmh o for s were performed. the compliance of the respiratory system (c rs ), blood gas exchange and the ventilatory settings (p plat , v t ) were recorded in both groups. o, respectively. the presence of rv dilatation was a strong predictor for the fo opening (p \ . ); on the contrary, no statistical significant difference was found between the site of injection (svc vs. ivc), the c rs , v t , and p plat and the presence or absence of a pfo. a high prevalence of pfo was found in ali/ards patients. rv dilatation seems to be the reason of this high prevalence. rv dilation may be due to the lower c rs and higher p plat of the ards patients. introduction. the clinical evaluation of arterial tone is mainly based on the calculation of total systemic vascular resistance (tsvr). however, given the pulsatile nature of arterial flow, this parameter provides an inadequate assessment of vascular tone. another approach proposed would take account of changes in pulse pressure and blood flow, relationship known as arterial elastance (ea). so, for a given stroke volume, the blood pressure generated in the circulatory system will depend on ea ( ). to assess the ability of the dynamic arterial elastance (ea dyn ), defined as the relationship between pulse pressure variation (ppv) and stroke volume variation (vvs), to predict the hemodynamic response in mean arterial pressure (map) to a increase in stroke volume (sv) in hypotensive preload-dependent patients with acute circulatory failure. we performed a prospective clinical study in a -bed multidisciplinary intensive care unit, including patients with controlled mechanical ventilation and monitored with the vigileo Ò monitor, for whom the decision to give fluids was taken due to the presence of circulatory, including arterial hypotension (map b mmhg or systolic arterial pressure \ mmhg), and preserved preload-responsiveness condition, defined as svv c %. dynamic arterial elastance (vpp/vvs ratio), arterial pulse pressure to sv ratio, map/sv ratio, tsvr and map were compared to predict a map increase c % after volume expansion (map-responders). results. at baseline, only ea dyn was significantly different between map-responders and nonresponders. ve-induced increase in map was strongly correlated with baseline ea dyn (r = . , p \ . ) and changes in ea dyn after ve (r = . ; p \ . ). the only predictor of map increase was ea dyn (auc . ± . ; % c.i.: . - ). a baseline ea dyn value [ . predicted an increase c % in map after fluid administration with a sensitivity of . % ( % c.i.: . - . %) and a specificity of % ( % c.i.: - %). conclusions. dynamic assessment of arterial elastance by pvv to svv ratio during controlled mechanical ventilation could be used to predict mean arterial pressure increase after volume loading in hypotensive preload-dependent patients. severe sepsis is one of the major reasons for intensive care unit (icu) admission and leading causes of mortality. some of these score systems have been customized for patients such as apache ii, apache iii, sasp ii and mods. this study is to assess the validity of mortality prediction systems in severe septic patients. objectives. the aim of this study was to compare and evaluate four severity scoring systems in intensive care unit (icu), including apache ii, apache iii, sasp ii and mods in severe septic patient. methods. fifty-six severe septic patients were divided into two groups. one was survival group and the other was non-survival group. besides general data, the continuous surveillance of apache ii, apache iii, sasp ii and mods were recorded by st, rd and th day. results. compared with survival group, mods was significant difference in non-survival group only in st day ( . ± . vs. . ± . , p \ . ) but apache ii, apache iii and sasp ii were significant difference through st, rd and th day(p \ . ). in seven-day comparison, p value of apache iii in non-survival group was the minimum (p = . ) and p value of mods was the maximum (p = . ). in optimal survival evaluation, it seemed that apache iii was the best (apache iii [ apache ii = saspii [ mods). conclusions. in order to evaluate the critical condition and prognosis of severe septic patients, apache iii was the best and apache ii and sasp ii were followed and mods was the worst. objectives. to assess compliance with the cem standards for management of severe sepsis across three ed sites in the west midlands. methods. data was collected retrospectively over months. patients presenting to the ed within this period were assessed for likelihood of severe sepsis by the diagnostic code given to each patient upon leaving the ed. data was analysed using a scanned copy of the ed clerking. patients' notes were assessed for sirs criteria and signs of new infection. if these criteria were met, and organ dysfunction was present, they were included in the audit. results. patients with severe sepsis were identified. of these % were documented as septic by ed staff. the cem standards of care were received in % of patients with a documented diagnosis of severe sepsis in the ed, and % of patients overall. % of patients received the 'treatment' aspects of care: oxygen, iv antibiotics (with blood culture) and iv fluids. % of severely septic patients had no documented consideration of icu referral. conclusions. early recognition of severe sepsis in the ed led to greater performance in meeting the cem standards. although % of patients received observations and % received the treatment interventions, we performed poorly in meeting the remaining cem standards. the trust has developed a severe sepsis proforma which incorporates the cem standards to accurately record the completion of each intervention. a sepsis course for staff has been launched trust wide, and a formal referral process to icu for all severely septic patients is being implemented. objectives. to observe association of body temperature (bt) and antipyretic use with mortality in the critically-ill. a prospective multi-national, multi-center observational study. consecutive patients whose icu stay were expected to be more than h were recruited from centers in japan and centers in korea. patient's bt was prospectively recorded every h until patient's death, discharge from the icu or up to days. information including patient's clinical characteristics at admission, presence of infection, and use of steroids, extracorporeal circuit, and antipyretics were recorded. ( ). while blood culture results take time, treatment for bloodstream infection should be provided swiftly, usually before results are available ( ) . prior treatment with antimicrobials increases the chances of false negative results. haste, poor technique and alteration in commensal flora may increase the chances of falsely identifying pathogens. objectives. we have investigated the utility of blood culture tests in our general critical care unit over year in terms of results yielded and actions prompted. methods. the indication for blood culture was clinician's discretion. all critical care sourced blood cultures for the period oct to sept were reviewed from the microbiology laboratory database. blood culture specimens were collected in bact/alert Ò bottles (biomerieux, durham, nc, usa ). notes review was made of the positive blood culture episodes to determine actions after the results were known. consideration was given to the source of the blood sample: clean stab versus from an intravascular device. categoric data was analysed using the chi-squared test and p value of . was accepted as significant. objectives. we hypothesized that in the emergency department of our hospital many patients with sepsis are not recognized as such. methods. in a retrospective design, patients of an age of years and older who were admitted to the emergency department during a period of months between january-april and diagnosed as having an infection were included. the diagnose infection was made on admission by the emergency department nurse. the included patients were either classified as having sepsis or not having sepsis, according to the sirs criteria. conclusions. h n infection was associated with significant morbidity and mortality. it occurred mainly in young pts with co-morbidities and was associated with severe hypoxemia, a trigger for prolonged mechanical ventilation and frequent use of lung rescue therapies. a significant delay in hospital admission and start of antiviral therapy should also be noted. admission to administration time difference between cycles was . h, with a mean reduction of . h between clinician assessment and prescription time in cycle two. we identified delays against the standard after both cycles of the audit. we demonstrated that the method of prescription should be taken into consideration when prescribing antibiotics in patients with suspected sepsis. there are a multitude of factors that could contribute to a reduction in the clinician assessment to prescription time, which may be investigated in further audits. conclusions. despite high levels of resistance among psa and ab from these icus, cfr for most carbapenem dosing regimens were above the reported susceptibility. doripenem provided greater cfr than meropenem, which was superior to imipenem against these isolates. while higher doses combined with prolonged infusions significantly improved cfr against psa, alternative therapeutic strategies will be required to address these highly resistant ab. grant acknowledgment. the passport study is supported by a grant from janssen-ortho-mcneil. introduction. drug interactions are common, and the effects of these interactions can range from innocuous to deadly. critically ill patients often receive a variety of potent drugs, including antimicrobials, making this population extremely susceptible to drug-drug interactions. therefore, physicians must be familiar not only with the antimicrobial drugs capable of producing adverse drug events, but also their potential drug-drug interactions. there are scarce data about the incidence of these types of drug interactions and the how frequently it might cause adverse events. objectives. the purpose of this study is to evaluate the incidence of potential drug interactions involving antimicrobials and the possibility to cause adverse events. the clinical pharmacist has prospectively analyzed icu prescriptions between january and december with the purpose to identify potential drug-drug interactions involving antimicrobials. the screening was done with the relief from a software (epocrates rx Ò drug reference). the interactions detected were classified in eight groups according to the affected system (neurological, cardiovascular, gastrointestinal, renal, endocrine, hematological, musculoskeletal and others) and through the type of interaction (pharmacokinetic, pharmacodynamic and others). we have identified the most common potential effects, the medications involved and have observed the incidence of adverse drug events. results. the icu admitted patients during the study period. we have analyzed physician orders with prescribed items. we have identified antimicrobial drug interactions ( different interactions) which compound % of the total drug interactions (n = ). the cardiovascular system and the pharmacokinetic interaction were the most potentially affected ( %; %). the most common medications involved were: fluconazole ( %), clarithromycin ( %), levofloxacin ( %); linezolid ( %). the clinical pharmacist has made an intervention regarding medication safety in % (n = ) and the acceptance rate by the medical icu staff was %. we have not been able to identify any adverse drug event caused by drug interaction even with our active search and the spontaneous reports. however, sub notification must be taken into consideration. conclusions. clinicians should be aware of potential drug-drug interactions when making therapy selections for critically ill patients. antimicrobial drugs are susceptible to interact with other drugs, which may increase the risk of adverse drug events. the clinical pharmacist interventions may improve clinical outcomes by optimizing medication use, monitoring potentially preventable adverse drug events and promoting information about this important issue to the icu multi-professional team. introduction. cefazolin is one of the most frequently administered antimicrobial agent for prophylaxis in ''clean'' surgery. its broad spectrum against gram + micro-organisms and its pharmacological characteristics make it an easy-to-use choice to prevent infections caused by staphylococcus aureus and coagulase-negative stapylococci. objectives. the aim of this study is the evaluation of the plasma concentrations of cefazolin administered as a prophylactic antimicrobial agent during cardiac surgery with cpb. adequate cefazolin plasma levels can maintain a tissue concentration high enough to prevent the risk of developing post-operative infections. after obtaining ethical committee approval and personal written consent, two groups of patients were enrolled in this prospective study. the first group, patients, received cefazolin, g, - min before skin incision and g adjunctive dose after h. then, three g doses were administered every h. in the second group of patients the adjunctive g cefazolin dose was given at the beginning of the cpb. blood samples were collected immediately before the first dose and every hour for the whole time of surgery, and, only in the second group, after surgery, at th, th and th hour. plasma cefazolin concentration was determined with a biological radial diffusion assay. results. plasma cefazolin was constantly higher than the mic of the most involved micro-organisms (according to clsi). in the first group, cefazolin concentration suddenly decreased after starting cpb. the g adjunctive dose immediately restored it. the earlier administration of this dose in the second group prevented this sudden fall. plasma cefazolin was maintained at effective inhibitory levels for the whole time of surgery in all patients ([ mcg/ml). during the postoperative period cefazolin decreased slowly, but inhibitory plasma levels were always maintained. the rate of cefazolin clearance was found equal to the creatinine clearance in all patients. perioperative plasma cefazolin concentration conclusions. the administration of cefazolin g every h can guarantee effective inhibitory plasma concentrations during surgery and during the first h after surgery. cpb causes a sudden fall in cefazolin plasma levels. this can be avoided administering an adjunctive g dose immediately before starting cpb. objectives. vancomycin dose regimen was adjusted based on trough plasma levels in burn patients that were distributed according to the extension total burn surface area (tbsa); also pharmacokinetics changes were compared. methods. twenty seven adult burn patients of both sexes, requiring antimicrobial therapy with vancomycin for the control of sepsis were investigated. pharmacotherapeutic follow up was performed in a serial of periods ( observations) for all patients investigated by collection of blood samples, ml each from the venous catheter as follows: st blood sample collection, h after the beginning of drug h infusion and a nd sample blood collection at the trough, immediately before the next dose. if necessary, additional sample blood collections were performed based on the laboratorial data for patients any time, for dose adjustment purpose and optimization of drug therapy. vancomycin plasma concentrations were determined by highperformance liquid chromatography. plasma curve decay was plotted, and pharmacokinetics was analyzed by one-compartment open model against the reference data reported. results. burn patients receiving the empiric dose regimen showed trough plasma level lower than the minimum effective concentration, consequently dose adjustment was required. vancomycin adjusted dose regimen showed statistical significance differences according to tbsa (p \ . ) as follows for daily dose normalized to body weight and expressed by mean ± sd: . ± . mg/kg/day were required for patients with tbsa below %, . ± . mg/kg/day for tbsa - % and . ± . mg/kg/day were required for tbsa above %. relevant changes on pharmacokinetics were observed by drug plasma clearance increased according the increase of tbsa (p \ . ), while the apparent volume of distribution and also the biological half-life remained unchanged. additionally, a weak correlation was observed between vancomycin plasma clearance and creatinine clearance (r = . ; p = . ), probably due to the contribution of the extra-renal clearance on total drug elimination. on the basis of data obtained in the present study and to prevent therapeutic failure and also to reduce the risk of bacterial resistance, dose adjustment in burn patients is recommendable based on vancomycin plasma monitoring and also on the extension of total burn surface area. introduction. the importance of early antibiotic therapy has been recently demonstrated. regarding a rapidly increasing number of obese patients, appropriate drug dosage in these patients is an important challenge of critical care since it has been shown that not only early start of antibiotics but also correct target concentrations decrease mortality. vancomycin is administered according to body weight (bw). nevertheless, little is known about the percentage of obese patients achieving pre-defined target serum levels within h after initiation of vancomycin therapy compared to patients with normal bw. objectives. therefore, it was the aim of our study to analyze the appropriateness of serum vancomycin levels in patients with a bw between and kg. vancomycin is almost entirely excreted by the glomerulus and may be responsible for nephrotoxicity [ ] . however, there is a lack of definitive evidence linking concentrations to either outcome or toxicity [ ] . few reports exist comparing intermittent dosing and continuous infusion. ingram [ ] suggested that whilst associated with a slower deterioration in renal function, there was no difference in the prevalence of nephrotoxicity. similarly, hutschala [ ] demonstrated worsening creatinine in patients following cardiac surgery with both intermittent and continuous infusion but infusion tended to be less nephrotoxic despite receiving higher doses. we wish also to report our experiences with vancomycin infusion in critically ill cardiac patients. methods. we examined retrospective data from , patients treated with vancomycin. we perform adjusted and un-adjusted analysis using sofa on the day of starting vancomycin and total dose received. to assess the differences in either an initial pulmonary or non pulmonary presentation. methods. prospective, observational, multi-center study conducted in intensive care (icu). we reviewed demographic and clinical data for all pandemic h n influenza a infections reported in the esicm h n registry. results. patients were screened from the registry. patients with completed data entry for pulmonary and non pulmonary with outcomes were identified and analysed. all patients had either suspected, probable or confirmed pandemic h n influenza a infection and were being cared for in an icu. % of the patients were male with a median age of (iqr - ) years. the admission mean saps score was ± and the apache ii score was ± . % of the patients subsequently received non invasive ventilation and % received invasive mechanical ventilation. the icu mortality rate was %. the hospital mortality was %. % of patients presented with a pulmonary presentation. % of these were admitted with ards and/or bacterial pneumonia and % with an acute bronchospastic exacerbation. % of patients were admitted to the icu with a non pulmonary presentation. the main reasons for admission in these patients were: cardiovascular instability ( %), altered level of consciousness ( %), renal failure ( %) and acute coronary syndromes ( %). patients with a pulmonary presentation were older, had a increased history of asthma or copd and were more likely to be ventilated. they had a higher mortality rate in the icu. non pulmonary presentations were more likely to suffer from chronic renal impairment. a total of episodes of pandemic influenza a (h n )v infections in critical care setting were analyzed: with bacterial pneumonia ( males and females) and with wheezing or viral pneumonia ( males and females). the mean age was (± ) years in patients with bacterial pneumonia and (± ) in patients viral pneumonia. the mean apache ii score was (± ) and (± ), with a corresponding probability of death of (± )% and (± )%. comorbidities were common, but without significant differences between the two groups (only exceptions pregnancy-more prevalent in patients without bacterial pneumonia-and dialysis dependence-more prevalent in patients with bacterial pneumonia). at icu admission shock and acute renal failure were more common in patients with bacterial pneumonia. in patients without pneumonia; severe hypoxia and ards did not presented significant differences between groups. aims. evaluation if an isocaloric beginning of artificial nutrition in critically ill medical patients is associated with increased nutritional related side effects compared to a hypocaloric start. methods. critically ill medical patients with an expected need for artificial nutrition of [ days were included into this prospective, randomized clinical study. artificial nutrition was started either isocalorically right from the beginning (group a; n = ) or hypocalorically ( % of the energy demands) followed by a stepwise increase over the next days (day : %); day : %) (group b; n = ). nutrition related side-effects were defined as the occurrence of hyperglycemia, hyperlactatemia, hypertriacylglycerolemia, upper digestive intolerance, cholestasis, or diarrhea as well as disturbances of serum electrolytes and were assessed on a daily basis. patients were randomized to receive either an artificial nutrition started isocalorically (group a) or hypocalorically followed by a stepwise increase (group b). of the patients, patients completed the study (group a: n = ; group b: n = ). the calculated, cumulative energy requirements of patients of group a and b were , ± , and , ± , kcal, respectively (p = ns). patients of group a received ± % and patients of group b ± % of the calculated energy requirements (p \ . ). the incidence of nutritional related side effects was not different comparing both groups, except for hypophosphatemia, which was more pronounced in group a. additionally, exogenous phosphate needs were higher in patients of group a. the number of interruptions of the artificial nutrition did not differ between groups. conclusions. an isocaloric start of artificial nutrition provided more energy during the first days of their icu stay than a hypocaloric beginning. there was no difference in the number of interruptions and in the incidence of nutritional related side effects, except hypophosphatemia suggesting the presence of refeeding syndrome. in studies carried on to demonstrate positive effects of glutamine (gln) that has innumerable biological features, the main point of discussion isn't whether gln has positive effects in sepsis but rather the effect difference between different administration routes. only enteral (en.) or parenteral (pn.) administration was analyzed in this respect and no studies on combined administration were performed. the primary endpoint in this study was to analyze the effects of administration of en. and pn. gln together or separately on intestinal mucosa + immune system in the experimental sepsis model. for this purpose villus atrophy, bacterial growth in blood and tissue, levels of blood gln, tnfa and il were examined. the secondary endpoint was to evaluate the different administration models in terms of cost. wistar, adult female rats were used. they were fed standard. sepsis was developed in groups (all rats) by injection of intraperitoneal(ip.) ml ( cfu/ml) e. coli. grup c (n = ):en./pn. isotonic saline ( ml/day; ml/d); grup e (en., n = ):en. gln ( . g kg - day - ) + pn. saline ( ml/d); grup p (pn., n = ):pn. gln ( . g kg - day - gln) + en. saline ( ml/d); group ep (en. ± pn., n = ):pn. gln ( . g kg - day - ) ala-gln = . g kg - day - gln) + en. gln ( . g kg - day - ); were administered. feeding of rats began h (h) after administration of ip e. coli. blood gln (with spectrophotometer), tnfa and il concentrations(with elisa) were examined at the start (baseline levels) and at - h after the experiment started. samples of tissue from mesenteric lymph node, liver, lung, blood and small intestine were collected. ala-gln = . g kg. . rates of reproduction of the strain administered were found lower for group ep than group c (p \ . ). rates of villus atrophy in ileum of group ep, p and e were lower than group c (p \ . ).plasma gln levels were found lower in groups ep and p at h, and higher at h than other groups (p \ . ). when plasma gln levels at h were compared with their baseline levels, significant increases were detected in groups ep and p and significant decreases were detected in groups c and e (p \ . ). serum tnfa and il levels were found lower for groups ep and p at and h when compared between groups (p \ . ). when serum tnfa and il levels at h were compared with their baseline levels, more distinctive increases were detected in groups c and e than other groups (p \ . ). significant positive correlation was determined between tnfa and il levels at h (p \ . ) and h (p \ . ). cost of simultaneous administration of en. and pn. gln was higher than en. administration but close to pn. administration at these doses. methods. medline and embase were searched. hand citation review of retrieved guidelines and systematic reviews was undertaken and academic and industry experts were contacted. only methodologically sound randomised controlled trials (rcts) were eligible for inclusion in the primary analysis. the primary analysis was conducted on clinically meaningful patient oriented outcomes, which included mortality, functional status and quality of life. secondary analyses considered vomiting/regurgitation, pneumonia, bacteremia, sepsis and multiple organ dysfunction syndrome. meta-analysis was conducted using the peto analytic method, which is known to minimize bias in the presence of sparse events. the impact of heterogeneity was assessed using the i metric. results. , unique abstracts were identified, resulting in the retrieval of papers for detailed eligibility review. four rcts were identified to be on topic however one rct reported excessive loss to follow-up such that an intention to treat analysis could not be conducted. analysis based on the three methodologically sound rcts demonstrated the provision of early en was associated with a significant reduction in mortality (or = . , % confidence interval . to . , i = ). no other outcomes could be pooled. sensitivity analysis including all four on-topic rcts (or = . , p = . , i = ), and a simulation analysis conducted using a different analytical method. (or exact = . , % ci . to . ), confirmed the presence of a mortality reduction. conclusions. although the detection of a statistically significant reduction in mortality is promising, overall trial size was small. the results of this meta-analysis should be confirmed by the conduct of a large multi-center trial. reference(s). results. the mean ibp was . ± . and mean igp was . ± . . correlation between the ibp and igp was significant however moderate (r = . ). analysis according to bland and altman showed a bias and precision of . and . mmhg respectively, however the limits of agreement (la) were large and ranged from - . to . mmhg. the median grv proto was ml ( - , ) and median grv classic was also ml ( - , ). correlation between the methods was excellent (r = . ). analysis according to bland and altman showed a bias and precision of - . and . ml respectively and the limits of agreement (la) ranged from - to mmhg. the median drainage time and return times were min ( . - ) and . min ( - ) for grv proto compared to min ( . - ) and min ( - ) for grv classic. a preliminary cost effectiveness analysis shows that the price of measuring grv with the classic method ranges from . € to . € per day, depending on the grv size. price of measuring grv with the gastro pv system is independent of grv size and is estimated at . € per day. the gastro pv system if priced at . € could become cost effective at grv of cc and more. conclusions. the interim results of an ongoing multicentre pilot study show that the gastro pv is a good alternative to the standard method for measuring grv. because the nurse can perform other tasks during drainage and return of the grv, and the fact that the system remains closed during measurement, this could be a major step forward in standardisation of grv measurement. furthermore it allows screening for intra-abdominal hypertension via igp estimation. acknowledgment. the gastro pv devices were provided by holtech medical, free of charge. introduction. the importance of early enteral feeding of the critically ill patient has been well documented. it is the more physiological approach, which is associated with lower rates of infectious complications. early enteral nutrition within h is recommended by the espen guidelines on enteral nutrition. a recent meta-analysis revealed that mortality and the incidence of pneumonia were significantly reduced in patients with enteral nutrition within h. parenteral nutrition may be associated with higher mortality. objectives. evaluation of a new technique for the placement of postpyloric feeding tubes by intensive care physicians. methods. prospective cohort study in critically ill patients subjected to transnasal endoscopy and intubation of the pylorus. attending intensive care physicians were trained in the handling of the new endoscope for transnasal gastroenteroscopy for days. a jejunal feeding tube was advanced via the instrument channel and the correct position assessed by contrast radiography. primary outcome measure was successful postpyloric placement of the tube. secondary outcome measures were time needed for the placement, complications like bleeding and formation of loops and the score of the placement difficulty graded from (easy) to (difficult). data are given as mean values and standard deviation. out of attempted jejunal tube placements, tubes ( %) were placed correctly in the jejunum. the duration of the procedure was ± min. the difficulty of the tube placement was judged as follows: grade : patients, grade : patients, grade : patients, grade : patients. in cases, the tube position was incorrect, and in another cases, the procedure had to be aborted. only in one patient, bleeding occurred that required no further treatment. conclusions. fast and reliable transnasal insertion of postpyloric feeding tubes can be accomplished by trained intensive care physicians at the bedside using the presented procedure. this new technique may facilitate early initiation of enteral feeding in intensive care patients. grant acknowledgment. the authors acknowledge the support of pentax, hamburg, germany, who provided the endoscope used in the study and of fresenius kabi, bad homburg, germany who provided the feeding tubes. a well-nourished condition before prolonged endotoxemia results in a better ability to adapt to endotoxin-induced metabolic deterioration of arginine-nitric oxide metabolism than does reduced caloric intake before endotoxemia ( ). the role of individual organs in the arginine-citrulline metabolism during malnutrition and sepsis is unknown and may be key to direct future interventions. to study the effects of reduced caloric intake and endotoxemia on the citrulline-arginine metabolism in the gut-liver-kidney axis. organ arginine-nitric oxide metabolism was measured by using a primedconstant stable-isotope infusion of [ n ]arginine and [ c- h ]citrulline during conditions; a -day reduced caloric intake feed regimen (starv; n = ), normal control feed regimen (co; n = ), endotoxemia alone (ce) and reduced caloric intake and endotoxemia (re) in. catheters for blood sampling were placed in the abdominal aorta, which, in combination with the catheters in the portal, hepatic and renal veins, served for metabolic measurements across the portal-drained viscera, liver and the kidneys, respectively. results. interestingly, re animals had similar citrulline appearance from the gut ( ± nmol/kg/min) compared to control and animals during ce, but higher in endotoxemia alone ( ± , p \ . ). this was related to a significantly higher no production from the gut in the re group ( , ± vs. ± , p \ . ). in the kidney arginine appearance from citrulline decreased significantly during re compared the control animals ( ± vs. ± nmol/kg/min, p \ . ). in contrast, the liver disposed more arginine in the re group compared to the other conditions, while no production was not higher. conclusions. despite reduced caloric intake prior to endotoxemia, the gut remains capable of increasing release of citrulline, although the capability of the kidney for the de novo production of arginine is severely compromised. metabolic control of the citrullinearginine metabolism in the gut-liver-kidney axis should focus on increasing de novo arginine production from citrulline. objectives. the aim of this study was to measure duodeno-caecal transit times of enteral feed in this patient group using a scintigraphic technique. a prospective observational study was performed in mechanically ventilated critically ill patients ( m, age ± yr, bmi ± kg/m , icu admission day ± , apache ii on study ± ; mean ± sd) and healthy subjects ( m, age ± year, bmi ± kg/m ). after a h fast a ml enteral feed (ensure kcal/min), labelled with mbq m tc-sulphur colloid, was infused into the distal duodenum over min. dynamic anterior scintigraphic images were recorded in min frames for min and the time of first appearance of activity in the caecum was recorded by two blinded operators (kj, ar). data were assessed using mann whitney u test and are presented as median (iqr). introduction. erythromycin, a macrolide antibiotic is widely used as a prokinetic agent in intensive care unit (icu) despite the lack of data supporting its prolonged effectiveness in enteral nutrition (en) intolerant critically ill patients. to evaluate impact on clinical outcome of erythromycin prescription as prokinetic agent in icu. all patients consecutively admitted from january through december mechanically ventilated for more than days and receiving en were included in an observational cohort study. en intolerance was defined clinically as a -hourly gastric residual volume (grv) c ml or vomiting. successful en was defined as a grv\ ml with a feeding rate c ml/h. erythromycin prescription was left to practician appreciation. objectives. this study aims at evaluating the relationship between diarrhoea and en in icu patients. methods. during month, the days with and without diarrhoea (c liquid stools/day) and the characteristics of nutritional support of all patients staying in our icu were recorded. patients staying \ h or presenting an intestinal stomy were excluded. we compared, between days with and without diarrhoea, total energy coverage and energy coverage by en as % of needs, en energy intake and en volume for each patient. needs were estimated as - kcal/kg body weight for women and men, respectively. the relationship between antibiotics, laxative treatment and diarrhoea was also analysed. results are presented as mean ± sd. comparisons were made by mann-whitney test. the risk of diarrhoea with en was calculated by odds ratio and confidence intervals (ci). the study included days of hospitalisation of patients ( ± years, bmi ± kg/m , sofa score at admission ± ). en was present in days of diarrhoea and days without diarrhoea. determining the small bowel function is of great concern in icu patients, because a malfunctioning small bowel may predispose to malnutrition and may increase the risk of sirs. a recently developed test, the citrulline generation test (cgt), measures the enterocytes' capability to convert glutamine into citrulline. the production of citrulline exclusively takes place in functioning enterocytes, therefore this conversion represents small bowel function. objectives. we aimed to define the cgt reference values in 'stable' icu-patients to assess small bowel function. secondly, we wanted to compare four different cgt methods; enteral and iv administration of dipeptiven and measurement of citrulline in both arterial and venous samples. we performed the cgt on stable icu-patients, defined as having respiratory failure but not dependent on vasopressors. they had a normal renal function and were able to tolerate enteral nutrition. a h fast was followed by administration of g of glutamine-alanine (dipeptiven Ò ) either intravenously or enterally, randomly determined. the next day the same test was performed by using the other route. after each administration of dipeptiven, citrulline levels, both arterial and venous, were measured at fixed time points using reverse-phase high performance liquid chromatography (hplc). results. nine females and males were admitted to the icu with either a medical ( ) or a surgical ( ) diagnosis. they had a mean (± sd) age and bmi of . ± years and . ± , kg/m respectively. their median apache ii score was . (iqr = . - . ). on the day the cgt was performed their median sofa score was . (iqr = . - . early post-pyloric feeding has been shown to improve clinical outcomes [ ] . commonly used methods for placing a nasojejunal tube (njt) are blind, endoscopic or fluoroscopic placement. the later two methods are relatively invasive, expensive and can cause delay to feeding, whereas blind placement is often unsuccessful. electromagnetic sensor guided njt insertion is a bedside technique able to confirm successful placement without the need for abdominal x-ray. the system incorporates a liquid crystal display and a receiver unit. the receiver is placed over the patient's xiphoid process and picks up the signal from an electromagnetic transmitter located at the tip of the feeding tube. the screen provides a visual aid to enable the operators to trace the route of the tube tip and identify its' location according to anatomical markers. objectives. we were interested to determine the suitability of electromagnetic sensor guided njt insertion especially in relation to success rate and procedure time. methods. fifty patients were referred for electromagnetic njt insertion on units at the leeds teaching hospitals. insertion time was measured from oesophageal visualisation until post-pyloric placement. various positional manoeuvres were employed along with administration of sedatives, prokinetics and air insufflation when applicable. all insertions were carried out by experienced investigators. all njt insertions were confirmed by abdominal x-ray. data collection included patient demographics, hospitalisation and procedural information. results. forty male and female patients, mean age (range - years), bmi mean ( - ), had attempted electromagnetic njt placement. patients had been hospitalised for a median of days ( - ). indication for njt insertion was either large aspirate and/or reflux ( %). seventy six percent of patients had an artificial airway and % of patients were receiving sedation. forty six percent of patients received metoclopramide and % air insufflation. thirty six percent of patients were moved into either left or right lateral position. successful post-pyloric placement was achieved in % of patients confirmed by additional abdominal x-ray. procedural time varied from to min (mean ). two of the placement failures were due to patient intolerance. conclusions. bedside electromagnetic guided njt placement technique is an acceptable method of placing post pyloric feeding tubes with a high success rate. gastrointestinal failure (gif) score has been suggested ( ). the gif score defines gi failure as the occurrence of feeding intolerance (fi) and intra-abdominal hypertension (iah) simultaneously. to compare the outcome of patients with primary vs. secondary gif. methods. all consecutive, mechanically ventilated (mv) patients treated for at least h during january to december in two icus were studied. gif was defined as gif score equal or above points according to the gif score ( ). points = fi and iah simultaneously; points = abdominal compartment syndrome (acs). fi was defined as the need to stop enteral feeding for any clinical reason (vomiting, high gastric residuals, bowel distension etc). iah was defined as mean intra-abdominal pressure (iap) c mmhg on any day. acs was defined as iap [ mmhg with the new onset organ failure. when gif developed in a patient with primary pathology in abdomino-pelvic region it was classified as primary gif, when occurred without previous pathology in abdomino-pelvic region it was taken as secondary. objectives. in this study the biochemical quality and prion safety of the pharmaceutically licensed plasma octaplaslg Ò was evaluated. the prion reduction factor achieved by western blot was confirmed by animal studies. eighteen consecutive batches of octaplaslg Ò (octapharma ppgmbh, vienna, austria) were tested on global coagulation parameters, fibrinogen levels, activities of coagulation factors and protease inhibitors, activation markers, as well as von willebrand factor multimers. in parallel studies, plasma pool was spiked with exogenous spike material, derived from brains of hamsters infected with hamster-adapted scrapie k, and a down-scale of the octaplaslg Ò manufacturing process was performed. the prp sc reduction factor for the resin was investigated in both western blot and hamster bioassay studies. a reduction factor of c . log prp sc was found for this process step by western blotting. the outcome of the hamster bioassay confirmed that the high level of removal prp sc seen during octaplaslg Ò manufacturing was equivalent to a removal of infectivity ( . log ). in octa-plaslg Ò , a parallel reduction of the s/d virus inactivation step led to significantly higher activities of plasmin inhibitor. our studies demonstrated that the same amounts of prp sc and prion infectivity bind rapidly and with a very high affinity to the chromatography resin. octaplaslg Ò has the same clinical safety and efficacy profile compared to that demonstrated by octaplas Ò over the last years, except for the increased safety margin in terms of prion disease transmission and the possible effect of a significantly increased plasmin inhibitor activity. uniplas Ò is a second generation solvent/detergent (s/d) treated, coagulation active plasma for infusion produced with an implemented prion removal step. it was developed as an alternative to the blood group specific s/d plasma products, octaplaslg Ò and octaplas Ò , in order to obtain an universally applicable (i.e. blood group independent) plasma that can be used without taking into account the blood group of the recipient. due to an initially controlled, optimal mixing of plasma of different blood groups prior to s/d treatment, in uniplas Ò , the blood group specific antibodies (anti-a and anti-b of both igm and igg type) are neutralised and/or removed by free a and/or b substances and red blood cells (rbcs) to a clinical acceptable level with very limited or no complement activation. objectives. in this study an extensive biochemical characterisation of the first uniplas Ò validation batches was performed. methods. three batches of uniplas Ò were produced by octapharmappgmbh (vienna) under production conditions in [ ] [ ] . uniplas Ò batches were tested on all important coagulation factors, protease inhibitors, activation markers, adamts and factor h levels, as well as von willebrand factor multimers. in addition, anti-a and anti-b titres of igm-and igg-type were investigated. finally, complement activation products, as well as key components of the complement system, were measured. results. in uniplas Ò batches, all coagulation factor activities were higher than . iu/ml and all protease inhibitor activities, including protein s and plasmin inhibitor, were higher than . iu/ml. uniplas Ò contained standardised levels of adamts and factor h, within the normal ranges for single-donor freshfrozen plasma. there was no activation of fvii obtained during manufacturing, thrombin-antithrombin (tat)-complex, prothrombin fragments (f + ) and d-dimer levels were within the normal ranges. anti-a and anti-b titres were within the uniplas Ò specification, i.e. anti-a igm and anti-b igm\ : as well as anti-a igg and anti-b igg \ : , respectively. uniplas Ò did not contain an increased amount of immune complexes and the manufacturing of uniplas Ò associated with more complement activation than the one seen for octaplaslg Ò . conclusions. the present study confirmed that uniplas Ò displays the same high quality and clinical efficacy as the s/d treated blood group specific plasma octaplaslg Ò , but with the additional advantage in being a blood group independent universally applicable plasma. most pts received more fluids than calculated by parkland formula ( ± . ml/kg %tbsa). interestingly, nonsurvivors received less ( . ± . vs. . ± . ml/kg %tbsa). gastric decompression, ascites drainage and the implementation of a stool protocol with rectal enemas ( interventions in pts) was able to remove . ± . l of body fluids and this was related to a significant decrease in iap and cvp and an improvement in oxygenation and urine output ( conclusions. pris is a difficult condition to diagnose and routine monitoring of the adverse effects of high-dose propofol remains sub-optimal. hypothermia has been reported to alter propofol pharmacokinetics and we propose that active cooling may increase the risk of developing pris. this may be particularly relevant in patients with tbi who are on high doses of propofol to control icp in addition to concomitantly administered catecholamines to maintain cerebral perfusion pressure. we recommend that further research is required in this area in view of the increasing use of induced hypothermia in icu. objectives. to compare differences in fluid resuscitation based on direct or indirect admissions to the london burns unit. methods. admissions to the burns unit with [ % burned surface area (%bsa) were identified over years. were excluded from analysis due to palliation or death within the first h. sets of notes were randomly selected for analysis of fluid balance in the first h period of fluid resuscitation after the burn injury. results. mean (sd) time from burn injury to arrival at the burns unit was lower for patients transferred direct to the burns hospital rather than via another hospital ( . ± . vs. . ± . min p = . ). mean (sd) error in burn size estimation was lower for patients initially treated by burns specialists versus non-burns specialists ( ± . vs. . ± . %, p = . ). all patients were resuscitated according to the parkland formula calculated at one of , or ml/kg/%bsa. the mean (sd) actual fluid volume differed from the target by . % (± . %); the lower the calculated fluid target, the greater the error between actual and planned resuscitation volumes; there was no difference in accuracy of fluid resuscitation at h between patients initially managed by burns specialists versus non-burns specialists ( . ± . vs. . ± . % respectively, p = . ). conclusions. burned patients transferred directly to specialist burns care receive a faster and more accurate assessment of their burn injury. despite this, we found no difference in fluid targeting errors at h, though this may reflect corrective fluid management on arrival at the specialist centre. echocardiography is an useful and minimally invasive tool that allows to know the heart filling pressures, also it has proven highly accurate in predicting the response to volume in critically ill patients. we try to determinate the response to fluid infusion by static variables as cvp or lap, comparing with the variation of ivc. methods. an observational prospective study with patients undergoing coronary cardiac surgery ( patients were excluded by a no presenting a good echo views), in the postoperative period under mechanical ventilation (vt ml/kg, fio %, peep ). we performed an echocardiography if the patient presented hypotension, just before the habitual fluid load protocol were started ( ml hes % in - min). we collected data before and after the infusion, and determine the responsiveness to volume if the cardiac output increased more than %. data in the report included invasive cvp and lap, and echo measures, ratio e/e', diameter and variations of inferior vena cava (ivc) and variations of stroke volume by echocardiography (Ølvot x vti lvot) and with vigileoÒ system. . the correlation between low values of cvp/lap and volume response was poor, the relationship between cvp below mmhg with increased cardiac output had a correlation (pearson correlation - . ) with a significance ( -tailed) . , and the relationship between lap \ mmhg and an increase in cardiac output had a correlation (pearson correlation . ) with a significance of ( -tailed) . . the measurement of the variation of the inferior vena cava, led us to calculated a cutoff point more sensitive to determine which patients were responders to volume. through the roc curves (sensitivity/specificity), with the area under the curve of . % (se = . %) and with a confidence interval of % (p significance of . ), resulted in a % variations of ivc with a sensibility of % and specificity of % (younden's index of . %). the same calculation, based on kraemer's quality indices (qi) gave us a % of variation in ivc, with a w = . specificity rather than sensitivity (qi . ), and with a w = . sensitivity rather than specificity (qi . ) objectives. to ascertain whether postoperative hypothermia is linked to high or low risk surgical patients. we conducted a prospective systematic analysis looking at the incidence of postoperative hypothermia in adults who underwent general anaesthesia. children age \ , pregnant women and patients undergoing regional anaesthesia were excluded from the survey. to identify the current level of doctors' knowledge on perioperative fluid management. methods. the survey was conducted at george eliot hospital, nuneaton, uk in may . questionnaires consisting of ten multiple-choice questions on basic sciences and clinical scenarios were devised by a consultant anaesthetist. these were personally distributed to doctors of all grades working in anaesthetics and the surgical specialties. doctors were asked to complete the questionnaire within min. of the questionnaires distributed, were completed. results. the mean questionnaire score varied between specialties from % in the anaesthetics department to % for doctors in surgical specialties. the mean score of registrars and fy doctors in surgical specialties was found to be and % respectively. the overall mean score was %. of all doctors surveyed, the daily maintenance water requirement was known by only %, % knew the daily maintenance sodium requirement and % knew that of potassium. the electrolyte contents of . % sodium chloride and hartmann's solution was answered correctly by % and % respectively. there is a significant deficiency in doctors' knowledge on perioperative fluid management. more emphasis on optimal perioperative fluid management is required in undergraduate and postgraduate training. increased awareness of the british consensus guidelines on intravenous fluid therapy for adult surgical patients would aid training. based on this survey, a regional online survey of junior doctors is planned to further identify gaps in perioperative fluid management training. optimal fluid management could also help to reduce prolonged hospital stay which can result from fluid-related complications. objectives. to evaluate dynamic echocardiographic parameters as predictors of volume responsiveness in surgical patients. methods. patients were included in the study after laparotomy surgery performed on the same day ( breathing spontaneously and mechanically ventilated in volume controlled mode with tidal volume of ml/kg). a fluid challenge was performed in spontaneously breathing patients by passive leg raising and infusing saline ( ml/kg). echocardiographic analysis of respiratory changes of inferior vena cava diameter (ddivc) and aortic blood flow (dabf) was performed in all patients. a threshold of % for ddivc was used for classifying patients as volume responders or non-responders. age, sex, gender, bmi, cvp, iap, map, left ventricular ejection fraction, left ventricular systolic and diastolic area, and stroke volume in all patients, as well as itbvi, ci, ppv and svv in patients were measured. a positive correlation with ddivc was established for itbvi (r = . , p = . ), iap (r = . , p = . ) and ef (r = . , p = . ). a positive correlation with dabf was not established for any variable measured. patients ( %) were classified as volume responders and ( %) as non-responders. responders had overall higher iap than non-responders ( . ± . mmhg vs. . ± . mmhg respectively, p = . ). respiratory changes of ivc diameter showed positive correlation with itbvi. so, conclusions about itbvi could be indirectly made from ddivc values in patients who are not being invasively monitored. ppv and svv did not show positive correlation with itbvi. surprisingly, we confirmed a positive correlation between ddivc and iap. we detected patients with high iap, while all the volume responders had overall higher iap. although further investigations are needed to establish how longer duration of high iap may influence ddivc, it seems that ddivc is a good parameter of volume responsiveness during first h after laparotomy surgery. unlike from other studies, we could not establish a positive correlation between dabf and any variable measured. these studies were performed in hypovolemic septic patients, so this could be the reason for such different results. more studies are needed in a larger set of patients undergoing laparotomy surgery to evaluate dabf. introduction. fluid optimization after major cardiac surgery was shown to improve patients postoperative outcome significantly. several hemodynamic parameters were proposed for the guidance of therapy but never compared in a head to head trial. objectives. in this prospective randomized trial patients scheduled for elective cardiac surgery underwent early goal directed fluid therapy guided either by stroke volume variation (svv) or by oxygen delivery index (do i). we hypothesized that while svv is easier to obtain it will not be inferior to do i in outcome parameters. methods. following ethics committee approval and signing of a written informed consent, patients were randomized in two groups to undergo either fluid optimization guided by do i or svv in the first postoperative hours in the icu following elective cardiac surgery (cabg). following a standardized egt protocol the parameters were collected by using hemodynamic monitoring based on a pulse contour analysis and a transpulmonary lithium dilution (lidco plus, lidco,uk). we compared amount and type of volume infused, need and amount of inotropic or vasopressor substances, time spent on ventilator, los in the icu and postoperative complications. statistics were evaluated by using a t test for unpaired samples. table . compared to the do i group fluid optimization using svv showed reduced ventilator times (p = . ) and less complications (p = . ) in the first days after surgery. no differences between the groups were detected concerning the type and amount of volume infused, need for inotropes or vasopressors or the los in hospital conclusions. while svv is less invasive, cheaper and easier to be obtained than do outcome was at least not inferior and even showed improvements in postoperative cardiac surgery patients. rd esicm annual congress -barcelona, spain - - october s introduction. over the years, there have been concerns over incompatibility of transfused blood with various intravenous fluids during blood transfusion, especially related to increased levels of haemolysis. it is often impractical, particularly in an emergency situation, to flush through a giving set with a so-called ''safe'' fluid prior to and after delivering blood. we wanted to investigate whether this is actually necessary and whether the usual fluids used in the perioperative period really do cause any demonstrable alteration in the composition of transfused blood. objectives. the purpose of this study was to expose packed red cells to a variety of different intravenous fluids commonly used during the perioperative period and to measure a number of parameters in the blood following their contact with each different fluid, including a blood film to examine for clumping of cells or haemolysis. a unit of a positive blood was passed through blood giving sets which were primed with various intravenous fluids. after adequate mixing of blood with fluids, samples were collected for full blood count, urea and electrolytes and blood films. one millilitre of mixed blood was taken in each bottle at a time. the intravenous fluids used in this study were normal saline, hartmann's solution, % dextrose, % dextrose, starch and gelatin. there was no significant rise in blood parameters suggestive of haemolysis. the potassium and ldh levels were not significantly different with various fluids. the haemoglobin and haematocrit levels were also comparable to one another. there was no demonstrable changes in blood parameters suggestive of haemolysis, nor were there any change in electrolyte values. this suggests that all of the fluids investigated during this study would be suitable to be used via the same giving set before and after the transfusion of pack red cells. objectives. to assess the compliance with the national guidelines in avoiding inadvertent peri-operative hypothermia in an acute district general hospital in england. we prospectively studied our local practice on maintaining normothermia in consecutive adult surgical patients { men, mean age . years, patients with asa grade ( . %), emergency surgical patients ( . %), patients with significant cardiac disease . %}. we used a questionnaire that was filled pre-operatively by anesthetic nurses, intra-operatively by anesthesiologists, and post-operatively by recovery nurses. patients were recruited from the following surgical subspecialties: general surgery ( %), gynecology ( %), trauma ( %), breast surgery ( %) and orthopedics ( %). day surgery patients were excluded. peri-operative hypothermia was defined as temperature \ °c as per the nice guidelines. results. less than half of our patients ( . %, n = ) had their temperature measured preoperatively, on whom incidence of hypothermia was . % (n = ). only one of these patients was warmed prior to induction. patients requiring emergency surgery and those with asa grade had increased incidence of preoperative hypothermia ( . % and . % respectively, p \ . ). based on nice guidelines, patients needed intraoperative forced air warming but only ( . %) patients received it. intraoperative temperature measurement was made on patients, of whom . % (n = ) were hypothermic. incidence of intraoperative hypothermia was high in surgical procedures lasting longer than min (p \ . ) but was not affected by the use of regional anesthetic techniques. patients had their temperature measured on arrival to recovery of whom ( . %) were hypothermic. patients ( . %) had their temperature measured every min (nice recommendation) and the mean time interval for temperature measurement in recovery was min. patients were still hypothermic on leaving recovery. conclusions. majority of our surgical patients did not receive adequate perioperative care on maintaining normothermia. consequently, the incidence of hypothermia was significant pre-, intra-and post-operatively. we are currently analyzing the data to investigate the effect of hypothermia on duration of recovery stay, length of hospitalization and mortality in our patients. we completed a double-blind randomized trial in patients undergoing cardiac surgery in which we compared fluid resuscitation with a hydroxyethyl starch (hes, % mw pentastarch) and saline. use of hes resulted in markedly less use of catecholamines the morning after surgery. an underlying design principle was that assessment of cardiac index (ci) is essential for a proper fluid protocol. in this analysis we examine that supposition. all subjects had pulmonary artery catheters. patients were consented preoperatively, but randomized post operatively to receive up to blinded ml boluses for predefined hemodynamic targets; ci \ . l/min/m , blood pressure (bp) set by admitting team, cvp \ mmhg, or urine output \ ml/h. hemodynamic measurements were made before and after each bolus. after the study boluses, only saline was used. results. patients received fluids, hes and saline. there were study boluses, hes and saline. of these, boluses ( %) could not be assessed for this hemodynamic analysis (but were still used for the primary outcome) because of protocol violation or missing data. of the rest, ( %) of boluses were given for a low ci; in bp and cvp were also low so that ci was the only trigger in %. a low bp was a trigger in ( %). low cvp was the trigger in ( %). only hes and saline patients required the maximum allowed blinded boluses. at the th bolus, low ci was the trigger for ( %) of hes but ( %) of saline patients. there were that could be evaluated for hemodynamic response based on four possible outcomes of cvp and ci. objectives. the aim of our study was to evaluate the predictive value of cvp with regard to gedi, and to correlate these parameters to cardiac index (ci). conclusions. volume depletion according to gedi was found in more than half the patients. the predictive values of cvp with regard to volume depletion were low gedi and its changes significantly correlated to ci and its changes, which was not observed for cvp. therefore, gedi appears to be more appropriate for volume management during mayor liver resections. introduction. regional anticoagulation with citrate is an effective and established anticoagulation strategy during crrt in critically ill patients, especially in surgical patients with a high risk of bleeding and in case of a heparin-induced thrombocytopenia ( ). however, citrate crrt could be associated with major metabolic derangements such as metabolic alkalosis, hypocalcemia, hypernatremia and citrate toxicity. objectives. the aim of our study was to investigate efficacy, safety and metabolic stability during citrate crrt in critically ill patients with acute kidney injury. methods. the retrospective study was performed in a mixed surgical and trauma icu in a university hospital. patient charts were reviewed for demographic data, the period and dosage of citrate crrt and metabolic parameters. reasons of admission, comorbidities and severity of illness were also evaluated. citrate crrt was performed using commercially available equipment and fluid solutions (multifiltrate Ò with integrated ci-ca Ò -system; fresenius medical care; germany). to maintain stable metabolic and haemodynamic conditions we used an internal standard protocol for citrate crrt. statistical analysis was performed using descriptive methods (mean, median and standard deviation) and a mann-whitney u test where appropriate. p \ . was regarded as statistically significant. conclusions. although minor metabolic imbalances were observed, none led to a termination of citrate crrt and all of them could be managed by adjustments of blood flow and dialysate rates according to a preset protocol. our findings suggest citrate crrt to be a safe and effective strategy for crrt even in patients with hepatic dysfunction. nevertheless, metabolic parameters need to be monitored regularly to avoid severe metabolic derangements. introduction. the liver is central to ammonia metabolism, being the main site of urea cycle enzyme pathways. in acute liver failure (alf) and decompensated chronic liver disease (cld) ammonia dysmetabolism results in hyperammonaemia, thought to be of central importance in the pathogenesis of hepatic encephalopathy and, in alf cerebral oedema [ ] . continuous renal replacement therapy (crrt), commonly used in critically ill patients may be an effective method of clearing ammonia. little is known of the efficacy such techniques have on ammonia clearance. objectives. to quantify the clearance of ammonia using an aquarius haemofilter (ahf) using different renal replacement doses and techniques. methods. patients with a circulating ammonia level[ lmol/l due to commence crrt were enrolled. the ahf was programmed to run in either pre-or post-dilution modes at a blood flow rate of ms/min using a . or . m filter depending on the crrt ultrafiltration (uf) dose, which included , or ml/kg/h (adjusted for ideal body weight). ml of blood and effluent fluid were collected, on ice into lithium/heparin and serum separation tubes, from pre and post filter access points and effluent tubing to calculate urea and ammonia clearance using the cordoba formula [ ] . delta whole body ammonia clearance was determined by measuring arterial ammonia at and min. ammonia measurements were performed using a pocketchem Ò blood ammonia bedside testing machine. results. patients ( alf and cld) were recruited (mean age years, sd ( ), with mean arterial ammonia lmol/l, sd ( ). min whole-body ammonia clearance was - lmol/l, p = . , paired t test). ammonia and urea clearance were correlated (r = . , p = . ); uf rate correlated negatively with filtrate ammonia (r = - . , p = . ) and positively with ammonia clearance (r = . , p = . ). filter ammonia clearance was not dependent on filter size for the standard blood flow rate. pre or post dilution modes did not affect ammonia clearance (p = . , student's t test). a constant filter size and blood flow rate achieved ammonia clearance of ml/min/m for ml/kg/h, ml/min/ m for ml/kg/h and ml/min/m for ml/kg/h (p = . , one way anova). conclusions. ml/kg/h based on ideal body weight appears to be the optimum dose of crrt for ammonia clearance when using a blood flow rate ml/min and a . m filter. filter and delta whole body ammonia clearance may be increased further using the combination of a higher dose ( ml/kg/h) with a larger filter size and higher blood flow rates. introduction. malnutrition is common in intensive care following the catabolic state induced by critical illness. patients who progress from enteral nutrition back to oral feeding are usually in an energy deficit. espen guidelines recommend increasing calorie delivery during the recovery period to cover this anabolic phase. oral nutritional supplements (ons) are widely used to facilitate calorie delivery within the hospital setting however the effectiveness of this strategy is dependent on patient compliance with the products. compliance among the elderly ward-based population has been considered ( ) however that of intensive care patients has not been reported. to evaluate compliance to ons in a mixed medical and surgical adult intensive care unit (icu) in a district general hospital. prospective observational study was conducted over a month period with data compiled from fluid chart analysis and discussions with nursing staff. all adult icu patients prescribed, or offered without prescription, an ons were included until the point they were discharged to the ward. the supplements studied, resource Ò energy, . fibre, fruit and dessert (nestlé nutrition), were selected based on their availability within the trust. patients were offered a choice of flavour. results. data was collected and analysed for patient days. a total of supplements were prescribed. of the prescribed supplements, . % were offered to patients and . % consumed. % were offered the same at nursing discretion based on clinical need and . % were consumed. resource Ò energy was the most frequently prescribed and offered product ( . and . % respectively). most common flavours selected by patients were strawberry and vanilla. resource . fibre was better tolerated ( . %) than resource energy, resource fruit and resource dessert ( . , . and . % respectively). across all products the best tolerated flavours were apricot, chocolate and coffee ( %). the highest calorie supplement, resource Ò . fibre, resulted in the best compliance in both tested flavours. compliance with ons demonstrated here is higher than previous studies ( ) partly attributable to one-on-one nursing of icu patients enabling active encouragement with feeding. nursing staff discretion had better uptake than routine prescription of ons. however, difficulties with ons still remain. interestingly in our study the highest calorie density supplement was tolerated the best and thus giving the most benefit to the patient. despite the difficulties associated with ons uptake we would recommend its regular use on icu with a drive towards the highest calorie supplements being offered. introduction. cirrhosis is a chronic disease and the patient's quality of life is affected in a negative way due to the problems like ascites, jaundice, nutrition deficiency, fatigue, activity intolerance, itching, pain, insomnia, anxiety, hopelessness, work loss and depression. objectives. the aim of this study is to examine the changes in patient's lives that diagnosed with cirrhosis of the liver disease owing to the symptoms they experienced. methods. this research is a qualitative study that has been carried out with inpatients diagnosed with liver cirrhosis in the gastroenterology clinic of a teaching and research hospital. average age of patients was (ranging - ). descriptive characteristics form and semi-structured interview form were used in the data collection. interviews with patients have been performed individually and face to face. the data were evaluated by using colaizzi's phenomenological data analysis method. as a result of the data analysis, three categories and six themes were identified. categories include: (i) problems of symptoms related to the physical limitations (ii) psychosocial issues. patients suffer mostly from fatigue and malaise ( patients), while those in the later stages suffer from, additionally, physical ailments caused by acid. inability to sleep due to anxiety and increase in tendency to sleep in advanced stages have been identified after being diagnosed. the majority of patients were identified to have undergone an anxiety besides having a fatal disease due to concern for the future, being forced to quit the job and being affected by the experiences of the patients in advanced stages. it also has been discovered that the patients had experienced social isolation because of fatigue and weakness in particular. as the result of this study it has been determined that patients with cirrhosis have mainly problems of fatigue, weakness, sleep disorders, anxiety and associated problems. rd esicm annual congress -barcelona, spain - - october s [ ] . while in patients with acute liver failure, elevation of arterial ammonia levels has been linked to cerebral complications and increased mortality, the role of arterial ammonia in hh patients is unknown. our study aims at evaluating arterial ammonia levels in patients with hh. furthermore, we wanted to elucidate the potential consequences of high ammonia levels in these patients. arterial ammonia levels were measured and documented in hh patients without liver cirrhosis who were admitted to the medical icu. icu mortality and overall day-survival were documented. cox regression was performed to describe the impact of ammonia levels on mortality. mann-whitney test was used for comparison of metric variables. results. overall median arterial peak ammonia level in our patients was lmol/l ( . - . lmol/l), whereas median arterial peak ammonia value was significantly higher in icu non-survivors compared to survivors ( ( - . ) vs. . ( . - . ); p \ . ). saps ii and sofa score were significantly higher in icu non-survivors (p \ . and p \ . , respectively). cox regression revealed that arterial peak ammonia levels were significantly associated with higher -day-mortality (p \ . ), even after adjustment for saps ii. median arterial peak ammonia levels in patients with verified brain edema were significantly higher than in patients without ( . lmol/l ( - . lmol/l) vs. . lmol/l ( . - . lmol/l); p \ . ) after exclusion of patients following cardiopulmonary resuscitation with consecutive hypoxic brain damage. our results suggest that increased levels of ammonia are associated with high mortality and can lead to brain edema in patients with hh. % of patients had a diagnosis of sepsis and % of patients were admitted under the neurosurgical team, the latter of which may have contributed to the relatively low anticoagulant use of %. systemic heparinisation was the sole anticoagulant used, but compliance with local protocols was poor with % of appts below the therapeutic range and % of infusions commenced at the wrong rate. % of filter changes were due to clotting and mean filter life was h. despite this, dose delivery was acceptable, with % of prescribed dose delivered. conclusions. as previously reported , our demographic data confirm the relatively poor outcome of patients needing crrt. we have identified areas where care for these patients could be optimised and endeavour to do this locally via improved protocol design and an ongoing educational programme. many of the components of crrt could be incorporated into care bundles, but certain aspects of treatment remain controversial which may be a barrier to their adoption. given the high numbers of neurosurgical patients in our unit, consideration should be given to the use of regional anticoagulation such as citrate. introduction and objectives. accurate prognostic indicators of patient survival in an intensive care unit (icu) help guide clinical decision making. factors known to portend poor prognosis in acutely ill cirrhotics in icu include the need for mechanical ventilation, development of shock, renal failure and sequential increase in the number of failing organs. while serum lactate is now an established marker of survival and/or the need for transplantation in fulminant liver failure, its impact on critically ill cirrhotics is less well known. methods. we retrospectively studied consecutive acutely ill cirrhotics admitted to the icu between and at the royal free hospital, a tertiary referral centre in liver diseases and transplantation. data were collected on demographic variables, aetiology of liver disease, liverspecific prognostic scores [child-turcotte-pugh (ctp), model for end-stage liver disease (meld), united kingdom model for end-stage liver disease (ukeld)], and acute illness scores [acute physiological score and chronic health evaluation (apache ii), sequential organ failure assessment score (sofa) ]. in addition, serum lactate levels at , and h were also recorded. multivariable logistic regression analysis was performed, and the discrimination ability of each of the above-mentioned scoring models in predicting icu and hospital survival of these patients was evaluated using the area under the receiver operating characteristic (roc) curve. conclusions. one third of lt recipients present a documented bacterial infection within year after surgery. we found a high prevalence of ciprofloxacin resistance and a low incidence of s.aureus witch was often resistant to methicillin. non fermentative gram negative bacilli represent % of the pathogens and should be taken in account for treatment of the most severe patients. extracorporeal liver support therapy is in its infancy but is valued as a detoxification treatment option for patients with cirrhosis who have rapid worsening of their liver function. we report the use of prometheus Ò , a new extracorporeal liver support system allowing the removal of protein bound and water soluble toxins by fractionated plasma separation and absorption (fpsa) in a patient with wilson's disease (wd) who developed rapid worsening of their liver function. a -year-old female patient, diagnosed with wd since the age of , was initially treated in an irregular pattern with penicillamine. therapy was discontinued. now, years later, she developed acute decompensated liver failure with hepatic encephalopathy with a meld . liver transplantation (lt) was the treatment option for this patient. but, in this case, the rapid and adverse evolution of the liver failure with renal failure and the unknown waiting time for a emergency liver donor in our country led us to use the extracorporeal liver support therapy. after h min of therapy we reduced the amount of bilirrubin for less than a half, we increase the urinary output and next day the patient went to liver transplant, stable, with a renal function improved. conclusions. acute liver failure due to wd is most of the time fatal without emergency lt. this case report highlights discontinuation of chelants treatment in a patient with wd. as the patient progressed to decompensated liver cirrhosis with encephalopathy, lt was the only treatment option but while we don't get a donnor, we can use, for a short period of time, an extracorporeal liver support therapy as a very useful bridge. results from two studies presented at the recent easl congress have shown that treatment with extracorporeal devices may not confer a survival advantage for severe liver failure patients, despite positive dialysis effects. however, results among a small sub-group of patients show promise like severely ill patients with hepatorenal syndrome type or a meld score over . ( ) . metoclopramide is used to stimulate the upper gi tract and seems to have no effect on colonic motility. objectives. the aim of this in vitro study was to compare the prokinetic potency of those substances. a tissue bath with guinea pig colonic segments fixed on a polyacrylic tray allows the evaluation of the transit time (tt), the time necessary for a wooden pellet to perambulate. a decrease of the tt reflects stimulation, and an increase inhibition of peristalsis. after stable peristalsis activity the effect of increasing concentrations of prucalopride, neostigmine or metoclopramide on tt were evaluated. dose response curves were constructed, two way anova (sigma stat) was used for statistics, p values b . were considered to be significant. effect of prucalopride and neostigmine on motility results. prucalopride stimulates normal peristalsis in vitro only in the highest tested concentration of lm (p \ . ). neostigmine's prokinetic effect was limited to a small concentrations range ( . lm, p \ . ), the concentration of . lm had a moderate, but not statistically significant prokinetic effect and the highest tested concentration ( lm) lead to a complete block of peristalsis (fig. ) . metoclopramide, as expected, was devoid of any effect on colonic motility. conclusions. this experimental setting is a reliable method to evaluate the effect of different substances on colonic motility in vitro. prucalopride's prokinetic activity is concentrations dependent and limited. neostigmine is well known to improve colonic motility, but it seems imperative that the drug's effective dose range be use-higher concentrations have inhibitory effect on peristalsis. objectives. robotic radical prostatectomy involves extreme changes in patient position and often associated with a longer operative time than other commonly performed laparoscopic procedures. this review discusses the anesthetic considerations in robotic radical prostatectomy while analyzing potential risk factors related to pulmonary complications. we retrospectively reviewed the medical records of all the patients who had undergone robotic radical prostatectomy at our institution. among the total patients of , aged to years, patients were capable of spontaneous respiration at the end of surgery (group i) whereas patients needed assist ventilation (group ii). the demographic characteristics, coexisting diseases, anesthesia and operation time, anesthetic agents, the amounts of blood loss, infused fluid and transfused blood products were compared between the groups. results. the mean age of the patients was . ± . years. the mean operation times were . ± . min (range, - min). age, body mass index (bmi) and asa status did not differ significantly between the two groups, whereas operation time, the amount of blood loss and the incidence of transfusion were significantly higher in the group ii. although patients with subcutaneous emphysema and atelectasis needed prolonged ventilator care for h, the incidence of atelectasis and subcutaneous emphysema was similar between the groups. conclusions. prolonged laparoscopic surgery in a steep trendelenburg position has a high possibility of postoperative respiratory insufficiency and the possible contributing factor is a long operation time. objectives. we examined the frequency of postoperative cough reflex and its effect on postoperative clinical outcome retrospectively. we examined the patients who admitted into the icu after the esophagectomy with lymphadenectomy during the period from september, , to february, . in addition to usual criteria for extubation we removed their tracheal tube if the cough reflex was identified when one milliliter of half saline was distilled into their trachea. if the cough reflex was absent until days after the operation the patient underwent tracheostomy and after that they weaned from the ventilator. results. there were patients (f/m / ), and their mean age was . ± . . cough reflex were confirmed by seventh postoperative day in patients ( %) but residual patients underwent tracheostomy because of absence of cough reflex ( introduction. the technique of laparoscopic cholecystectomy carried with carbon dioxide pneumoperitoneum may lead to adverse events in mechanical, hemodynamic and respiratory systems as a consequence of physiopathological changes such as increased intraabdominal pressure. _ it may cause hypoxemia, hypercapnia, hemodynamic instability and impairment of oxygenation. decreased functional residual capacity, ventilation/perfusion imbalance and sympathetic stimulation effects of co that is absorbed from peritoneum are basic problems. in perioperative period, application of mechanical ventilation and anesthesia should be reviewed because of these physiopathological mechanisms. in this study, we aimed to investigate the effects of cmh o peep application on etco , minute ventilation and arterial oxygenation during laparoscopic cholecystectomy operations. for this reason, the study included total patients and they were randomly divided into two groups. same anesthetic protocol was applied in both groups. for general anesthesia induction; mg/kg dose of fentanyl, mg/kg dose of propofol were administered. following this procedure endotracheal intubation was applied with . mg/kg dose of cisatracurium. patients received % o -% n o (mixture with equal amounts) with . - . mac end-tidal sevoflurane for anesthesia maintenance. before co insufflation, respiratory parameters were recorded on the respiratory apparatus adjusting etco - mmhg, respiration rate /min., inspiration/expiration rate : , vt: - ml/kg. patients were ventilated by volume controlled mechanical ventilation. heart beats, mean arterial blood pressure and peripheric o saturation (spo ), etco , minute ventilation(v) and peak airway pressure(p _ ip) values of all patients were recorded just before insufflation (t ). after recording, cmh o peep was applied to the first group (group ). peep wasn't applied to the nd group (group ). these parameters were repeated in periods such as (t ) and (t ) minutes after insufflation, preexsufflation (t ) and postexsufflation (t ) in both groups. before insufflation, respiration rate ( /min) and etco ( - mmhg) values were adjusted as planned in both groups and minute ventilation was also adjusted. at the same time, total insufflated amount of co for distending abdomen was recorded. arterial blood gas analyses were made just before induction (while patients were breathing normal room air, t ), min after induction (t ) and just before the end of the operation (t ). in our study, we found that minute ventilation to stabilize etco - mmhg was significantly increased in group in which peep was not applied (p \ . ). none enhancement was needed in minute ventilation in group and arterial oxygenation was significantly increased in group (p \ . ). aside from the cholesterol lowering effects of statins, as a class of drugs they have been shown to exert anti-inflammatory effects and have the potential to be therapeutic in neuroinflammatory disorders . we tested the hypothesis that atorvastatin improves memory retrieval post unilateral nephrectomy in a murine model. methods. c /bl mice were randomly allocated into groups (n = - /group): control plus placebo, control plus atorvastatin, nephrectomy plus placebo and nephrectomy plus atorvastatin. animals were given either a placebo ( . ml normal saline) or lg in . ml normal saline of atorvastatin by gavage once a day for days. on day all animals underwent fear conditioning training using a conditional stimulus of a db tone and an unconditional stimulus of a . ma electric shock. on day the surgical animals underwent unilateral nephrectomy, whilst the control animals received no surgery. at post-surgical day all animals were tested for hippocampal dependent memory retrieval using the fear conditioning paradigm, with freezing response to the db tone as a marker of memory retrieval. all animals were then terminated. results. surgery evoked a reduction in hippocampal dependent memory retrieval in the nephrectomy plus placebo group as measured by % freezing time (mean ± sd: ± ) when compared to the control plus placebo group ( ± ; p \ . ); a situation mimicking pocd. this change was obviated in the nephrectomy plus atorvastatin group ( ± ; p [ . vs. control plus placebo). conclusions. our data suggested that atorvastatin has the potential to improve postoperative cognitive performance in a murine model of pocd. the proven safety of the drug along with its already widespread use and cost effectiveness would permit rapid instigation of a human randomized controlled trial to explore efficacy in the clinical setting. a. puxty , r. docking glasgow royal infirmary, department of anasethetics, glasgow, uk hypotension in the post-operative period is common but guidelines recommend its prevention/treatment [ ] . epidurals are common practice following major surgery in many institutions and can prevent pulmonary complications [ ] but have also been associated with falls in blood pressure when compared to other analgesic techniques [ ] . fluids therapy is a common intervention for hypotension but fluid overload has been associated with worse outcomes in surgical patients [ ] . we decided to audit the incidence and management of hypotension in the surgical high dependency unit of a large tertiary referral hospital. to determine the incidence and management of hypotension in the surgical high dependency unit in pancreatic, upper gi and lower gi patients. we prospectively looked at patients who underwent major upper gi, lower gi or pancreatic surgery involving epidural analgesia. the first h of care from onset of anaesthesia was closely looked at with regards to fluid management, epidural management and actions taken on episodes of hypotension or severe hypotension (defined as systolic blood pressure of \ and \ respectively). each episode of hypotension was looked at to determine the actions taken at that point. of the patients looked at, were major pancreatic, lower gi and upper gi patients. ( %) had at least one episode of hypotension, with ( %) having at least one episode of severe hypotension. mean fluid in during the first h was ml, with a mean fluid balance of ml. there was no difference between the doses of epidural local anaesthetic in h between the hypotensive and non hypotensive groups (p = . ). management of hypotensive episodes was variable, but the most common intervention at episode one was fluid bolus ( %) and discontinuation of epidural was most common at episode two ( %). use of vasopressors for hypotension was very low with only two infusions being started altogether. conclusions. hypotension is very common in our high dependency unit. fluid balance in our patients was far more positive that we had expected. management of hypotension was variable. we plan to institute a protocol for hypotension and fluid administration to determine if improvements can be made. objectives. to identify predictive factors associated with the need for relaparotomy in patients with ssp. adult ssp patients undergoing laparotomy between and included within a single-center peritonitis registry (perit) were collected. patients subjected to relaparotomy were studied. we excluded patients with severe peritonitis secondary to appendicitis. apache ii and sofa score at icu admission after the initial laparotomy were recorded. variables with a p value. in a bivariate analysis were included in a multivariate logistic regression for further analysis of predictors for need for re-laparotomy. results. two-hundred forty-seven patients were obtained from perit registry. a total of patients with spp were included in the analysis. eighty seven patients ( %) required relaparotomy. median number of re-laparotomies was . most spp were associated to colon (n = , . %), small intestine (n = , . %) and biliary tract (n = , . %) perforations. cultures were positive in . % of first laparotomy: gram negative bacteria were isolated in . %, gram positive bacteria in . % and fungi in . %. hospital mortality was % (n = ). multivariate analysis is described in the table . conclusions. in obese patients scheduled for surgery, the previous use of cpap has not shown an improvement in blood gas parameters. the use of cpap in the hours before and immediately after surgery has not been associated with better postoperative oxygenation. combined icu-surgery dpt. action in these cases seem to contribute to better patient outcomes. objectives. we set out to quantify the intensive care workload and changes to that workload over the first years following the transfer of a specialist bariatric service to our hospital. a prospectively collected bariatric surgical database was cross-referenced to the itu database (ward-watcher) to identify admissions to the -bedded critical care unit of all patients who had undergone any bariatric procedure. for each patient identified; demographics, reason for admission, level of support, length of stay and outcome were recorded. data were grouped into -month periods for trend analysis. research in emergency situations and especially in resuscitation field raises important ethical and regulatory issues. the globalization of the resuscitation science through multicentric trials for example highlights the need for a more consistent approach to regulatory aspects to enable the science to grow while protecting human rights. objectives. the purpose of this analysis is to compare the different regulations approaches in emergency research in north america (canada, usa) and in europe (european directive, france). conclusions. this analysis emphasizes the lack of international standardization of regulatory measures and ethical decisions. however some countries like the us seem to advance in the democratic process by mandating additional regulatory measures (community consultation, public disclosure to the communities) prior to initiation of clinical investigation; nonetheless, there is little evidence of their effectiveness. many challenges are raised. firstly, the variability in regulations, and consequently in local board's assessments, is problematic, pleading for international regulations. secondly, the current heterogeneous ethical review process and demanding unsubstantiated regulatory measures poses a risk to all when it is not evidence based and it is applied inconsistently between countries, within a country and worse at the level of each individual hospital review board. it puts the investigator at risk for unnecessary criticism and the community at risk as it is unknown if we truly consult or inform our target communities about waiver of consent research through our current ethical and regulatory processes. globalization and evaluation of the ethical and regulatory processes are urgently needed; regulatory community has to work towards a standardized evidence-based process upon which to base regulatory decisions. introduction. in research outside the intensive care field it is known that a high score for the psychological factor ''perceived hopelessness'' experienced by healthy individuals increases risk of death several fold. objectives. the aim of this study was to examine if the score of the psychological factor ''perceived hopelessness'' may predict long term mortality (mean or high perceived hopelessness score) when assessed post icu care in former icu patients. methods. prospective, multicenter study in three mixed icu's in sweden. questionnaires, including the -item hopelessness scale, demographic data and previous illnesses, were sent months after discharge to all former adult icu patients who thereafter were followed for another years. a reference group of individuals from the uptake area of the hospitals served as controls. results. ( %) patients returned the questionnaires. the icu patients reported significantly higher mean scores in perceived hopelessness score compared with the general population, . (sd . ) compared with . (sd . ) (p \ . ), and % (n = ) of the icu patients perceived a mean or high hopelessness score compared with % of the general population (p \ . ). the icu patients who died during the follow-up period reported a significantly higher perceived hopelessness score (n = ) . (sd . ) (p \ . ) as compared with those who survived up to years after discharge (n = ) . (sd . ). in a logistic regression model the long term mortality for the icu group was found to be affected by: pre-existing disease [odds ratio (or): . ], age (or: . ) and perceived hopelessness score (or: . ). the new and interesting finding of this study is that icu patients score higher on ''perceived hopelessness'' than a control population and this increase is predictive for the post icu mortality. furthermore, the size of this effect is significant and only exceeded by pre-existing disease and age. we performed a retrospective observational study to evaluate what proportion of met calls was associated with lomt issues. to estimate the proportion of met reviews involving patients with a not-forresuscitation (nfr) order and the timing of met calls in relation to admission and death or discharge from hospital. to compare the patient characteristics and outcome for met calls associated or not associated with lomt issues. we obtained hospital research ethics committee approval. we performed a retrospective observational study involving five-year (august -april ) in a single tertiary australian hospital. we obtained information on demographics, on the met review and hospital outcome. lomt included nfr orders, not for met orders and palliative care plans. results. we analysed met reviews in patients. table and fig. summarize major findings for overall population and the two subgroups of patients with or without lomt. patients with lomt care plan were older, more likely to have medical diagnoses, were reviewed later during their hospital stay and closer to their hospital discharge or death. fewer lomt patients were admitted to icu. hospital length of stay was shorter, mortality in lomt care patients was double that of non-lomt patients. however, more % of patients with lomt were discharged alive from the hospital. conclusions. more than one third of met activations deal with lomt issues. although the mortality of these patients is high, a large proportion survives to hospital discharge. evaluation of the patient experience in intensive care (icu) frequently depends on reports from surrogates such as relatives. there is a concern regarding the validity of the surrogate opinion which might not represent the values of the incapacitated patient and treatment decisions therefore maybe biased [ ] . others have found that there is a strong preference within a population for utilizing relatives as surrogate decision-makers in the event of admission to icu and this attitude is not influenced by ethnicity, religion or education level [ ] . objectives. the objective was to measure the ability of the relative to answer on behalf of the patient. a further wish was to determine the validity of their surrogate responses. a retrospective study, which surveyed relatives of patients who had died within a critical care service during a -year period ( , ) . the item questionnaire allowed for the collection of quantitative and qualitative data with respect for each item to overcome the limitations of the quantitative format which may not be sensitive to all the issues which can surround the provision of end-of-life care [ ] . for items, relatives were asked specifically to grade their capacity to represent the patient. results. quantitative data from the items designed to test the relatives' perception of their ability to act as surrogates indicates that relatives considered they could respond to these items for % (average) of instances. when the relative did answer on the patient's behalf, the level of concordance between the surrogate (relative) and the patient's perceived opinion was % suggesting that when the relative is willing to act as surrogate the response is likely to have validity. (table ) . results from the qualitative data indicates that the low ( %) level of willingness to answer these questionnaire items reflected a reluctance to answer on behalf of a sedated or ventilated patient, rather than an inherent inability to represent the patient. conclusions. the response rate to the items vindicates concerns regarding the ability of relatives to represent the patient in icu settings and supports a need for further study. where the relative is willing to act as surrogate, concordance does exist. qualitative data clarified quantitative results and was instrumental in promoting a better understanding of the concerns of relatives who have a family member admitted to icu. . the majority of patients that died in icu were provided some kind of therapy restriction. an important conflict strains between clinical practise, bioethical principle and jurisdiction laws; the solution of this conflict is more and more urgent. therapy restriction has also important economical aspects since the number and cost of available treatments constantly increase. our survey studied therapy restriction procedures in hungary for the first time. in we performed a survey with questionnaire among intensive care physicians. questionnaires were sent out electronically to registered members of the hungarian society of anaesthesiology and intensive care. respecting anonymity we have statistically evaluated replies ( %) with t test and anova. we grouped intensive care physicians based on gender, years spent in work, religion and type of department they were working, and we compared data from these groups. intensive care physicians generally make their decisions alone, based on the patient's long-term life prospects and physical status ( . / points). they are slightly influenced by the opinion of the patient ( . ), the relatives ( . ) and other medical personnel ( . ). if the physician sees any chance of recovery but the patient or relative requests treatment restriction then . % of physicians that completed the forms would continue therapy against the will of the patient or relative. only . % would accept the patient's/relative's opinion and autonomy in such a case and would stop therapy. in fact . % of physicians would make their decisions without considering or even against the opinion of patient if they think therapy is useless. if there is no chance of recovery despite medical treatment % of physicians stop the treatment, . % would continue it without informing the patient or the relatives, . % informs the relatives but continues useless treatment irrespective of the will of the patient or relative. having analyzed the groups we found two significant differences. in case of useless treatment physicians working in university hospitals more often choose treatment restriction without informing relatives (p \ . ) then those working in non-university hospitals. physicians who declare themselves as atheist rather choose the continuation of treatment without informing relatives (p = . ). conclusions. the hungarian practise of end of life decisions among intensive care specialists is paternalistic, physicians make their decisions alone, do not consider the requests of the patient or relatives. our goal is to strengthen patient autonomy and to support their opinion by training icu physicians. on the other hand it is inevitable to define what useless medical treatment exactly is and to introduce this category in medical ethics and also in jurisdiction practise. objectives. to determine the frequency and processes of eol care at our centre. between october and december , / ( %) patients staying in the icu for more than day, underwent some form of eol care in the icu. icu staff notified investigators whenever an eol decision was made. we recorded demographic details, documentation of the eol care process in the case notes, and interviewed icu staff to determine the eol care processes involved. results. patients ( %) were male, ( %) were females. mean age was . ± years. icu stay was . ± . days, admission apache ii score was . ± . which increased to . ± . on the day of eol care decision. % patients had metastatic cancer. reasons for initiating eol care were refractory acute illness in %, advanced cancer in %, brain death in %, and lack of finances in %. eol discussions were initiated by the family in %, and by the icu medical team in % patients. families wanted to take the patient home to die. the icu consultant was involved in all discussions with the family, the primary consultants in % and primary team residents in %. nurses were involved in only patients. agreement on eolc was reached after discussion in %, discussions in %, and discussions in % of cases. documentation of the eol care process was not done in % cases. withholding of life support (wh) was practised in / patients ( %) and withdrawal of life support (wd) in %. intubation was withheld in . % patients, cardiopulmonary resuscitation in %, inotropes in % and dialysis in %. regarding wd, only / patients were extubated and the ventilator withdrawn in another / patients. inotropes were withdrawn in patients ( %). reduction of fio . without discontinuing mechanical ventilation was the commonest mode of wd, in patients ( %). all patients received morphine infusions during lols/wols. family members were present by the bedside in % cases. conclusions. wh is preferred over wd. documentation of the eol process does not occur in a significant proportion of cases. nurses are rarely involved in the eol care decision making process. legal issues may be barriers to good eolc in our icu, and perhaps in india. objectives. to know the point of view of the staff is essential to understand their beliefs, attitudes and decisions. brazilian private general icu with beds. the following items were analyzed: profile of the interviewed; their opinion about end of life questions: fear of death, fear of experience pain before death, the best place to die, advanced directives, decision-making process, therapeutic withhold of mechanical ventilation, nutrition, fluid management, antibiotics, vasoactives drugs, sedation and analgesia in patients which death is imminent and irreversible. results. about . % of our icu team answered the research (n = ). the mean age is . years (sd . ), . % of female, . % married, . % protestants and . % catholics and icu professional experience of . years (sd . ). using a visual analog scale ( , no fear to , the worst fear possible) the team pointed . as their fear of death; the fear of suffering pain before death was . . for . % of the responders, the best way to die would be with their lovely ones, no matter if at home or at hospital. only . % would prefer to die an icu. the majority of the team ( . %) would share the eol decision-making process with the family instead only by the medical staff ( . %). about . % would leave an advanced directive with their therapeutic preferences like do not resuscitation orders. the icu team agreed on the withdrawal of vasoactives drugs ( . %), antibiotics ( . %), nutrition ( . %) and mechanical ventilation ( . %) in patients out of treatment. our results showed the staff vision about their own death and their opinion about the end-of-life care issues. in developing country as brazil there is a still gap between everyday practice and the current legislation. fortunately, the debate about eol issues has increased in last years. the end-of-life discussions and decisions should begin by respect to points of view of all involved: patients, family, medical staffs with a legal support of the society's beliefs and expectations. prospective observational study conducted in greek multidisciplinary icus. we studied all consecutive icu patients who died, excluding those who stayed in the icu \ h or were diagnosed with brain death. patients comprised the study population [mean age ± (sd) years, mean apache ii score on admission ± ]. results. of patients studied, % received full support including unsuccessful cardiopulmonary resuscitation (cpr). % died after withholding of cpr, % after withholding of other treatment modalities besides cpr, and % after withdrawal of treatment. patients in whom therapy was limited had a longer hospital (p = . ) and icu (p \ . ) stay, a lower admission gcs score (p \ . ), a higher apache ii score h prior to death (p \ . ), and were more likely to be admitted with a neurological diagnosis (p \ . ). patients who received full support were more likely to be admitted with either a cardiovascular (p = . ) or trauma diagnosis (p = . ), and to be surgical rather than medical (p = . ). the most important factors affecting the physician's decision to provide full support were reversibility of illness and prognostic uncertainty; the physician's religious beliefs and legal concerns had minimal impact. the main factors guiding the decision to limit therapy were unresponsiveness to treatment already provided, prognosis of underlying chronic disease, and prognosis of acute disorder; old age was not a determinant, while economic cost and lack of icu beds seem to play no role. relatives' participation in decision-making occurred in % of cases and was more frequent when a decision to provide full support was made (p \ . ). the principal reason for not discussing end-of-life dilemmas with relatives was the fact that the family was thought not to understand ( %) advance directives were rare ( %). icus. however, in a large majority of cases, it involves the withholding of cpr only. withholding of other therapies besides cpr and withdrawal of support are infrequent. physician has a dominant role in decision-making. objectives. the primary objective of this study is to determine the prevalence of inappropriate or non-beneficial care in icu patients as perceived by their icu healthcare providers, as well as the reasons for this perception. second, we want to determine which factors are associated with the perception of inappropriate care. a descriptive survey design is used. a single-day cross-sectional evaluation of perceptions of inappropriate care among , icu healthcare providers in icu centres in european countries will take place on may th . questionnaires will be administered to icu healthcare providers (nurses, head nurses, junior and senior icu physicians) providing bedside care to adult icu patients on that particular day. in this study, inappropriate care is defined as a patient care situation that is similar to one or more of seven scenarios. these scenarios were created based on the literature and a multidisciplinary conference attended by experts in intensive care, geriatrics, and palliative care. . the cross-sectional study will take place on may th . preliminary results will be given at the esicm conference. we have designed a one-day cross-sectional study to record inappropriate or non-beneficial care in european icu's. results will be available for the esicm conference. grant since the introduction of the mental capacity act in the uk in , the impact within research in the intensive care environment has not been elucidated. since many of the patients are incapacitated and therefore unable to consent, it is now stipulated by the ethics committee that the researcher must make reasonable attempts to identify a consultee, failing this, nominate a person unrelated to the research project to be consulted. in order to comply with the mental capacity act, retrospective consent must be obtained, once the patient regains capacity. objectives. the aim of the study was to highlight the difficulties in obtaining retrospective consent, evaluate the methods used and demonstrate the adaptations made to increase retrospective consents. methods. this explorative analysis investigated the process of obtaining consent in patients enrolled in an observational study on critically ill patients. consent was obtained on admission if the patient had capacity. assent from the patient's next of kin or a legal professional representative was obtained before enrolment in patients who lacked capacity. after discharge from icu, a member of the research team re-visited these patients to explain their involvement in the research, its purpose, procedures, implications and any further participation required by the subject. at this point, the patient could consent or withdraw from the study. if the patient decided to withdraw from the study, all data collected and samples stored were destroyed. the researcher visited the patient for a minimum of two visits; firstly to explain the study; secondly to establish if the patient has retained the information and to gain retrospective consent. results. patients were recruited within the time period of which ( . %) died. in ( . %), consent was obtained on admission as the patients had capacity, ( . %) were discharged prior to obtaining retrospective consent, ( %) lacked capacity on the researcher's visits, and patient ( . %) withdrew from the study. patients ( . %) were successfully consented retrospectively. overall, the researchers performed visits to obtain from the patients for whom retrospective consent was required. conclusions. the process of recruiting patients who lack capacity within the intensive care unit is challenging and time consuming. stipulations set by the ethics committee to seek retrospective consent once the patient has regained capacity, has a major impact on research staff time and finances. detailed recommendations as well as guidelines how to assess capacity in the post-icu patient and how the assessment of capacity has to be applied to intensive care research are needed to fully comply with ethical and legal requirements. objectives. we wanted to know if patients expressed to surrogate decision makers, after icu discharge, specific resuscitation directives, and we have investigated any factors related to the patients and their illness or care process that might be associated with this. we reviewed patients admitted in the icu between december and may . a random sample of survivor patients has been defined. seven patients were excluded ( for language barrier, died, were no more reachable). fifty three patients took part in semistructured interview at - month post icu discharge. the questionnaire discussed in detail the aspects of advance directives. patients had also completed a quality of life questionnaire (euroqol d), and we calculated the eq- d visual analog scale. we reviewed medical records in icu data base: age, gender, length of stay, saps ii, bmi, length of ventilator support and central venous catheterization as well as prescription of transfusion, hemodialysis or adrenergic agonist. multivariate logistic regression was practiced to investigate any factor associated to expression of specific resuscitation directives after icu discharge. after icu discharge, % of interviewed survivors expressed specific resuscitation directives to an appropriate identified surrogate (written ''living will'' or oral statement). eq- d visual analog scale was ± . on multivariate regression analysis, only one studied variable was significantly associated to the post-icu expression of specific resuscitation directives: age (odds ratio = . , z = - . , p = . ). conclusions. after icu discharge, a majority of our patients expressed to surrogate decision makers specific resuscitation directives, especially the younger patients. our findings suggest that surviving to icu is an opportunity to specify oral or written directive, and both may help to illuminate future decision making from the patient's perspective. objectives. to explore the issues around eolc provision for cancer patients in a critical care unit through family, professional and patient experiences. to explore how a diagnosis of cancer impacts upon eolc provision for critically ill patients. a heideggerian phenomenological interview approach was undertaken, in order to gain personal experiences. families of those patients who died after decisions to forgo lifesustaining treatment (dflsts) were interviewed. patients who were seriously critically ill (apache ii [ or had received cpr) who experienced critical care were also interviewed, since patients' views about eolc provision are very rarely explored. doctors and nurses also contribute their vision for, and experiences of, eolc in a cancer critical care unit. thirty seven participants were interviewed. tensions between treating families versus treating patients impacted on timeliness of eolc. achieving a good death was possible through caring activities that made best use of technology to prevent prolonged dying. decision-making and eolc could be difficult to separate out which, in turn, affects prospects for eolc. three main themes included: dual prognostication; the meaning of decision-making; and care practices at eol: choreographing a good death. these themes outlined the essence of moving along a continuum toward patients' deaths and the impact that had on opportunities for care and a good death. conclusions. cancer affected the trajectory in unexpected ways. the trajectory could be very quick, especially in unexpected death and some newly diagnosed cancers. even in the face of a life-limiting and serious disease like cancer, death could be unexpected. the rapidity of trajectory related to cancer diagnosis, prognosis, withdrawal and patient demise significantly impacted on the potential for, and timing of, eolc. a sentiment of moving on from historical practices around critical care for cancer patients, and related poor prognoses, was overwhelmingly agreed on but important caveats in cancer prognostication remains. conclusions. these data suggest that oscillation settings of and hz provided more optimal pef/pif ratio ([ . ). our data also suggests that airway clearance using hfcwo may facilitate improved gas exchange in mechanically ventilated patients. further study is required to confirm these results grant acknowledgment. partial funding support in the form of devices was provided by hill-rom inc. a. esquinas , m. folgado , j. serrano hospital morales meseguer, intensive care unit, murcia, spain, hospital virgen de la concha, zamora, spain, hospital reina sofia córdoba, intensive care unit, cordoba, spain objectives: we hypothesized that the use of intrapulmonary percussive ventilation (ipv) could effect hypercapnia/acidosis and airway secretions control during treatment with noninvasive mechanical ventilation (nippv) in exacerbations of copd associated with bronchial secretions. prospective multicenter study. the study was performed in the medical icu of spanish university hospitals members of the spanish ipv working group. we enrolled copd exacerbation patients with secretions and the need for nippv in icu. criteria of exacerbations of copd are: a respiratory frequency c /min, a pao [ mmhg and ph b . . we define two ipv strategies as complementary treatment during nippv to evaluate the effects of ipv. strategy group i: nippv at first line and combination of ipv in early periods without nippv in spontaneous breathing and ph c . . strategy group ii: first line of ipv with mouthpiece/face mask and oxygenation previous to the application of nimv with ph \ . . in both groups daily sessions ipv were applied by for min/ day by mouthpiece or face mask during stay in icu. nippv was applied with bipap ventilator (respironics) and face mask with bipap mode. cardiopulmonary monitoring, clinical and arterial blood gases were evaluated. therapy was considered as successful when patients did not need nippv support and clinical and arterial blood gases returned to baseline. results. patients with copd exacerbation were admitted in icu for nimv, age ± years, male ( %) were excluded for severe hypoxemia (pao :fio b ) associated with pneumonia ( / ) and cardiac insufficiency ( / ). fifty patients were enrolled in the study. -up tilt-table rehabilitation better than sitting in a chair for ventilated adults in intensive care in terms of improving lung function? j. manners , a. thomas , s. boot , g. mandersloot barts and the london school of medicine and dentistry, london, uk physiotherapy intervention is a fundamental part of the patient stay in an intensive care unit (icu) and treatment is often aimed at maintaining/improving respiratory function. physiotherapists use the upright posture to elicit these improvements and sitting in a chair and standing with a tilt-table are commonly used interventions. to date there are no published reports comparing the efficacy of these interventions in ventilated subjects. • to compare the effects of these two positioning techniques employed with icu patients. • to measure changes in respiratory rate, tidal volume and minute volume during these positioning interventions. • to measure functional residual capacity during positioning interventions. • to measure the change in metabolic demand during positioning interventions. methods. convenience sampling of ventilated subjects meeting the inclusion criteria was employed. subjects acted as their own controls undergoing sitting in a trauma chair and standing on a tilt table at degrees in random order on the same day. respiratory rate (rr), tidal volume (v t ), ventilation (v e ) and oxygen consumption (vo ) were measured at minute intervals during baseline and intervention for min. functional residual capacity (frc) was measured once at rest and following each intervention. measurements were recorded using the ''e-covx'' module for the ''ge carestation ventilator''. results. subjects were recruited. no adverse events occurred during interventions. significant increases from baseline rr (p \ . ), v e (p \ . ) and vo (p = . ) occurred during the tilt table intervention. there was an increase in frc during tilting of . l which failed to reach significance. significant increases from baseline rr (p \ . ), vo (p = . ) and a decrease in v t (p = . ) occurred with the chair intervention. conclusions. these interventions are safe in a critical care population. increased muscular activity associated with upright interventions elicited expected elevations in vo . the tilt-table produced an increase in v e driven by an increased rr at the expense of v t . v e was not elevated during chair sitting despite an increased vo and was accompanied by an unexpected decrease in v t. introduction. uk guidelines about rehabilitation after critical illness highlight the need for outcome measures to determine patient progress and efficacy of treatment [ ] . there is no consensus about the most appropriate measures of patient function. the austoms [ ] tool was designed by therapists in australia to measure activity and function across nine scales assessing structural and functional difficulties and ability to perform activities. scales are split into four domains (impairment, activity limitation, participation restriction and distress/wellbeing) and scored from to with . intervals allowed. acceptable inter-rater variation is defined as an absolute difference of . . austoms has not been appraised in patients recovering from critical illness. objectives. to prospectively determine the inter-rater reliability of the austoms physiotherapy scales in adult patients who had undergone cardiothoracic surgery and required critical care admission for over days. methods. the therapy (physiotherapy and occupational therapy) team underwent a h teaching session using the austoms handbook prior to commencing the trial. austoms was then used over eight consecutive weeks during the weekly therapy goal setting meeting. each week a patient was selected to be scored using the most appropriate functional scales. the clinical history was presented to the team by the therapist leading the patient's care. therapists were then asked to independently score patients across the four domains for each scale. reasons underlying differences in scores were explored by group discussion. the difference between the th and th centiles of the initial scores was calculated for each domain as a measure of inter-rater variability. results. - therapists were present at each meeting. respiratory function and musculoskeletal movement related function were the most common scales used. the mean difference between th and th centiles was greater than . (± . ) for all domains. none of the scales/domains showed consistent inter-rater reliability over the week period. overall the activity limitation domains of each scale showed the least inter-rater variance of scores. clinical experience of therapist did not appear to influence scores. conclusions. the austoms outcome measure showed poor inter-rater reliability when evaluated over an week period on our intensive care unit. further work is ongoing to evaluate the ability of austoms to reveal changes over time when scored by therapists. introduction. uk guidelines on the rehabilitation of patients after critical illness highlight the importance of establishing and reviewing individualised rehabilitation goals for all patients that are at risk of developing physical and non-physical morbidity [ ] . our institution's practice is to create objective goals that are smart-specific, measurable, achievable, realistic and timed [ ] . objectives. the aim of this audit was to prospectively collect data regarding the setting of rehabilitation goals in a group of patients admitted to a cardiothoracic intensive care unit. methods. all consecutive patients admitted under the intensive care team in november were included. data regarding the timings of initial physiotherapy assessment, goal setting, and concomitant sedation were collected using a structured questionnaire completed by the treating physiotherapist. results. patients were admitted under the critical care team. patients were assessed by a physiotherapist within h of admission. of these , had smart goals set within a median of days of initial assessment (range - days). there was a correlation between level of consciousness and the number of days taken to set goals. patients who were fully conscious or drowsy on initial contact (n = ) had a smart goal set in a median of days. by contrast patients who were sedated/paralysed on initial assessment (n = ) had goals set in a median of days. initial goal setting did not include other therapists or the family. goals fell in to categories, range of movement, hoisting out to chair for periods of time, sitting on the edge of the bed, transferring out to the chair by standing and mobility goals-i.e. walking set distances. the maximal interval between reviews of the patients' goals was days. most patients had smart goals defined and regularly reviewed. however, despite physiotherapy assessment within h of admission, there was often a delay in setting these objective goals. the need for continuous sedation acted as a barrier to explicit setting of goals. the results emphasised the need to improve patient and family/carer involvement with initial goal setting in order to be compliant with uk standards. objectives. investigation of ems effects on muscle strength and exploration of issues in relation to handgrip dynamometry in icu patients. one hundred seventy two consecutive patients with apache ii score c , were randomly assigned to the ems (n = , age: ± years, apache ii: ± ) or the control (n = , age: ± years, apache ii: ± ) group. ems sessions applied daily in muscles of both lower extremities. the strength evaluation of various muscle groups of the upper and lower extremities was made clinically upon awakening with the mrc scale, ranging from to (normal strength) for each group. the same scale was also employed in the diagnosis of cipnm (mrc \ / ). a subgroup of these patients also performed handgrip dynamometry. results. fifty seven patients (ems: , control: ) were finally evaluated. ems patients scored higher than controls (p b . ) in wrist flexion, knee extension, ankle dorsiflexion and right side hip extension, while they tended to perform higher in all other muscle groups (p: . - . ) ( table ) . grant acknowledgment. this project has been co-financed by e.u. and the greek ministry of development. background. secretion removal is major aim of respiratory physiotherapy in intensive care. manual hyperinflation provides a tidal volume to the lungs that is greater than baseline. it is effective in secretion clearance and is frequently used [ , ] . there is a limited evidence that addressed the effects of combining rib-cage compression and suctioning on oxygenation, ventilation, and airway-secretion removal in mechanically ventilated patients [ ] . objectives. the aim of this study was to investigate the effects of manual hyperinflation administered in combination with expiratory rib-cage compression on lung compliance, gas exchange, and secretion clearance in mechanically ventilated patients. methods. twenty-two intubated, mechanically ventilated, and hemodynamically stable patients were studied. the patients received manual hyperinflation, with or without expiratory rib-cage compression, with a minimum -h interval between the two interventions. manual hyperinflation with or without expiratory rib-cage compression was performed for min before endotracheal suctioning. respiratory mechanics and hemodynamic variables were measured min before (baseline) and then and min after the interventions. arterial blood gases were determined min before (baseline) and min after the interventions. secretion clearance was measured as sputum weight. the two measurements were obtained on the same day. results. no significant differences were observed in gas exchange and secretion clearance between the two interventions (p [ . ). in each case, static lung compliance and tidal volume improved significantly at min post-intervention (p \ . ), whereas at min postintervention, only static lung compliance had improved significantly above baseline (p \ . ). our results suggest that the addition of expiratory rib-cage compression to manual hyperinflation does not improve lung compliance, gas exchange, or secretion clearance in mechanically ventilated critically ill patients. recently, there has been an interest in mobilization of acutely ill patients who are in an intensive care unit (icu). in the literature, the major safety issues while mobilizing critically ill patients has been outlined. cardiac reserve [(cr) (% of age predicted maximal heart rate)] and respiratory reserve [(rr), ratio of partial pressure of oxygen in arterial blood to the inspired fraction of oxygen (pao /fio )] are the important factors that can affect the ability to tolerate the mobilization. patient who has rr more than and cr lower than % is considered to have sufficient reserve to tolerate mobilization [ , ] . objectives. the aim of this study was to compare the effects of mobilization on respiratory and hemodynamic parameters in patients with sufficient and insufficient respiratory and/or cardiac reserve. mobilization events are divided into two groups (sufficient, insufficient) according to the pre-mobilization cr (sufficient, \ %; unsufficient, [ %) and rr (sufficient, [ ; insufficient, \ ). heart rate (hr), systolic/diastolic/mean arterial blood pressure (sbp, dbp, mabp), respiratory rate (rsr) and percutaneous oxygen saturation (spo ) were recorded from the monitor. respiratory and hemodynamic parameters were collected just prior to the mobilization, just after the completion of the mobilization when the patient had been returned the supine position and min of the recovery period and compared between the groups. a total of abdominal surgery patients ( male, female) received mobilization treatments in icu. the mean age was . years, mean body mass index (bmi) was . kg/m , mean apache ii score was . and mean icu stay was . days. mobilization events included ( %) sitting on the edge of the bed, ( %) standing, ( %) walking to chair and sitting in the chair. % ( ) of mobilization events had insufficient rr and % ( ) of mobilization events had sufficient rr. . % ( ) of mobilization events had insufficient cr and . % ( ) of mobilization events had sufficient cr. all respiratory and hemodynamic parameters were found similar in sufficient rr and insufficient rr group at all stages of the mobilizations (p [ . ). spo was higher, while hr and rsr was lower at all stages in sufficient cr group compared to insufficient cr group (p \ . ). resting hr and cr may affect the safety of mobilization, for this reason it is important to consider respiratory and hemodynamic parameters prior to and while mobilizing the icu patients. introduction. obesity is a chronic disease and a major health problem. obesity in critically ill patients is associated with a prolonged duration of mechanical ventilation and intensive care unit (icu) length of stay [ ] . objectives. the aim of this study was to investigate the effects of mobilization on respiratory and hemodynamic parameters in the critically ill obese patients. [ . kg/m )] were included as soon as their cardiorespiratory stability allowed mobilization protocol. mobilization was defined as sitting in the bed, sitting on the edge of the bed, standing, walking to chair and sitting in the chair. heart rate (hr), systolic/diastolic/mean arterial blood pressure (sbp/dbp/mabp), respiratory rate (rr) and percutaneous oxygen saturation (spo ) were recorded from the monitor. respiratory and hemodynamic parameters were collected just prior to the mobilization (supine position), just after the completion of the mobilization when the patient had been returned the supine position and min of the recovery period. all parameters were compared with initial values. the ratio of partial pressure of oxygen in arterial blood to the inspired fraction of oxygen (pao /fio ) was calculated from the arterial blood gas samples before and after the mobilization. introduction. the use of respiratory therapy for patients with a variety of lung disease is a standard in medical care [ ] , including in the intensive care unit (icu) setting [ ] . in this context, it is widely accepted the routine use of physical therapy in several situations in the intensive care, such as the care of critically ill patients not requiring ventilatory support, assistance during the postoperative recovery and the assistance to critically ill patients requiring ventilatory support [ ] . at present definitive recommendations cannot be made regarding the use of respiratory physiotherapy for decreasing relevant clinical outcomes in critical ill patients requiring mechanical ventilation. objectives. this study aimed to determine the impact of providing chest physiotherapy on the duration of mechanical ventilation, intensive care length of stay, intensive care and hospital mortality in mechanically ventilated patients. single-centre, randomized, controlled trial in a university hospital general intensive care unit (icu). were included in the study patients aged more than years, admitted to the icu needing mechanical ventilation for longer than h. physiotherapists provide group intervention (p) with the intensity and frequency of therapy they felt appropriate based on their assessment of the likely treatment benefit. control patients (group c) only received suctioning, decubitus care and general mobilization. results. primary outcomes were icu and hospital mortality regardless of the cause of death. secondary outcomes were length of icu and hospital stay, length of mechanical ventilation, weaning and extubation failure. patients in the p group more frequently achieved parameters to start weaning, but there were no significant differences between p and c groups on weaning and extubation failure, length of mechanical ventilation and length of icu stay. there was fewer hospital, but not icu, mortality in the p group. conclusions. we demonstrated that respiratory physiotherapy decrease hospital mortality and suggest that this effect was, in part, secondary to the effect of the intervention on weaning from mechanical ventilation. introduction. critical illness can cause diverse cerebral dysfunctions ranging from unconsciousness to minor cognitive impairments (mci). severe cerebral dysfunction, as delirium, is known to affect outcome after critical illness but it is uncertain whether minor impairments affect mortality or morbidity [ ] . objectives. the primary aim of this study was to estimate the incidence of mci in a group of general icu survivors immediately after icu stay and three and months after discharge. secondary we wanted to explore if type of cerebral dysfunction after icu discharge affected mortality and morbidity. methods. patients admitted to our general icu were included prospectively. we included patients. / ( %) were delerious and / ( %) were not delerious but had mmse \ after icu stay. of the patients with mmse c , were possible to classify as having mci or not. / ( %, % ci: - %) were found to have a mci after icu discharge. on and months these numbers were respectively: % ( % ci: - %) and % ( % ci: - to %) there was an increased risk of both death and being institutionalised at both and months regarding delirious patients and patients with mmse \ compared to patients with mmse [ . no such differences were found regarding patients with or without mci. (tables and ) . conclusions. the incidence of mci after critical illness is high on discharge but drops on and months after. severe cognitive impairments affect mortality and morbidity, but minor cognitive impairments do not. objectives. this study analyzes mid-term survival and risk factors associated with survival of patients undergoing cardiac surgery in son dureta hospital. methods. patients were consecutively operated from november to december . patients who were discharged alive from hospital were followed until december . we did kaplan-meier survival analysis and logistic regression study of variables associated with mid term mortality. results. in-hospital mortality was . % ( % ci: . - . %). information was available on , ( %) of , patients who survived until hospital discharge. at the end of the follow-up period, observed mortality was . % (ci %: . - . %). survival probability at , and years of follow-up was , and %, respectively. the mean time of follow-up was . years (range . - . ). patients c years showed a lower survival rate than patients \ years of age (log rank \ . ). age c years, history of severe ventricular dysfunction (ef \ %), diabetes mellitus, preoperative anemia and hospital stay were independently associated with mid-term mortality. conclusions. mid-term survival of patients alive after hospital discharge was very satisfactory. mid-term mortality varied according to age and several preoperative chronic diseases. a closed-ended questionnaire was developed by the nurse congress commission of the société de réanimation de langue française (srlf). an invitation to complete it online was sent by email to caregivers registered on the srlf push-list. results were analyzed by icu or by respondent. results. caregivers working in icus completed the questionnaire ( % were nurses, % were doctors, % were nurse's aides, % worked in adult icus and % in pediatric icus). % of adult icus (n = ) had unrestricted policy but % had a visiting time of less than h per day. at the opposite, % of pediatric icus (n = ) had unrestricted policies. % of the respondents working in icus with a visiting time \ h per day considered very useful or essential to enlarge visiting periods but % of them considered this enlargement as unhelpful. at the opposite, % of the respondents working in icus with unrestricted policy found very useful or essential to reduce visiting periods. % of caregivers working in icus with unrestricted policy but only % of caregivers working in other icus thought that an unrestricted policy was able to improve often or systematically the relations with families. moreover, only % of caregivers working in icus with unrestricted policy but % of caregivers working in other icus thought that an unrestricted policy disturbs the organization of care. % of respondents found very useful or essential to give information in a dedicated room whereas it was often or systematically done in only % of icus. identically, % of respondents found very useful or essential to give information to proxies with the patient's nurse whereas it was often or systematically done in only % of icus. some cares were often or systematically programmed for family participation in % of pediatric icus but in only . % of adult icus. indeed, proxies often or systematically participated in nursing in % of pediatric icus but never in adult icus. at the opposite, proxies often or systematically participated in tracheal aspirations in only % of pediatric icus and in . % of adult icus. conclusions. more than half of respondent's adult icus are closed but caregivers working in icus with unrestricted policy perceive it favorably. some improvements are also expected by caregivers on the use of dedicated rooms for information and on the participation of nurses in meetings with families. finally, participation of families to care is not a practice of french adult icu caregivers. methods. included: patients with dysfunction of two or more organs in the first h, admitted and discharged from icu during . excluded: neurocritical and politrauma patients. contact year following discharge; questions were asked concerning symptoms related to a period in intensive care that presented following discharge and which were not present prior to admission. in the case that the patient was not contacted, the next of kin was asked. results. patients included. general characteristics during admission to icu: % male; age . ± . years; sofa* ± . ; apache** ii . ± . ; apache** iv ± . ; length of stay in icu: . ± . days; . % were on invasive mechanical ventilation and . % on non-invasive mechanical ventilation. data collection was carried out over ± . months, on average months (range: - months). . % ( patients) had died at the time of contact. the person contacted was the patient in . % of the cases, the spouse in . % and immediate family (patient's parent/child/sibling) in . % of the cases. . % had difficulty sleeping following discharge from icu with an average time since discharge of . ± . months; . % suffered feelings of sadness and difficulty in finding enjoyment which had persisted for . ± . months; . % had experienced difficulty in concentrating over an average of . ± . months; . % had suffered some form of memory loss after discharge over an average period of . ± . months; . % presented with asthenia over an average of . ± . months; . % had arthromyalgia over a period of . ± . months; . % had experienced changes in appetite over an average of . ± months; . % had changes in intestinal habit over an average of . ± months; of which . % had diarrhoea, . % constipation, and . % both symptoms; . % presented with headache over a period of . ± . months; . % had tremors, that had not previously been present, over an average of ± . months; . % had experienced reduced vision, over an average period of . ± . months; . % presented with speech/ language problems, over an average period of . ± . months; . % exhibited newly presenting changes in micturition, over ± . months. another less frequently occurring symptom was loss of hearing ( . %). conclusions. severely ill patients that are admitted to icu frequently present with ''residual'' symptomatology following discharge, most notably arthromyalgia and asthenia. many of these conditions persist for months. intensive care unit (icu) readmission rates range from to %, in spite of initial recovery from critical illness. previous researches report that the revised acute physiology and chronic healthy evaluation (apache ii) score at either admission or discharge is an important predictor for readmission after icu discharge. however, there are a few papers concerning the association of discharge apache ii score with readmission after discharge from surgical intensive care unit. objective. we compared the ability of the discharge apache ii score with that of the admission apache ii score in predicting readmission, especially early readmission within h, after discharge from icu. conclusion. this study showed that both discharge apache ii score and admission apache ii score are useful predictors for readmission after icu discharge, but discharge apache ii score is only independent factor in predicting early readmission within h after icu discharge. introduction. health related quality of life (hrqol) is decreased in former icu patients. in research outside the intensive care field it is well known that the psychosocial factors, coping strategies and perceived hopelessness affect hrqol. however, the influence of coping and hopelessness on hrqol after intensive care is unknown. objective. the aim of this study was to examine how coping strategies and perceived hopelessness among former icu patients compares to corresponding in a reference group. we also evaluated the effect of coping and hopelessness and icu related factors on hrqol. methods. prospective, multicenter study in three mixed icu's in sweden. patient demographics, length of stay, apache ii score, reason for admission and time on ventilator were collected for all adult patients. questionnaires, including the coping instrument pearling-schooler mastery scale (pms), the -item hopelessness scale, sf- , demographic data and previous illnesses were sent months after discharge from hospital to the patients. the reference group (n = , ) was a random selection of persons from the same catchment area as the study patients. . ( %) icu-patients, - years, returned the questionnaires. the patients reported significantly lower mean scores in coping . (sd . , p \ . ) and higher perceived hopelessness . conclusions. this study indicates that coping strategies and perceived hopelessness are important for the hrqol of previous icu patients. however, the magnitude of these effects are smaller than that of pre-existing diseases. introduction. mortality on a medical intensive care unit (icu) is estimated to occur in about % of patients. its association with age, severity of illness and comorbidities is well established. for other diseases like coronary artery disease it has been shown that pre-existing depression is a risk factor for worse outcome. the role of depression regarding the outcome of icu patients has not been investigated so far. we studied the association between pre-existing depression and mortality in medical icu patients and present preliminary data of this ongoing study. objectives. assessment of a possible association between mortality of icu patients and prevalent depressive mood at time of icu admission. the primary endpoint was -day mortality. methods. prospective cohort study. all patients admitted to a medical -bed icu in a university hospital, older than years, were eligible. postoperative patients and patients who had an expected length of stay below h (survey) were excluded. patients whose cognitive function allowed appropriate comprehension and response answered the hospital anxiety and depression scale (had). prevalent depressive mood at admission was defined by a score c in the depression dimension. all other patients were assessed by observer rating by next-ofkin. in this case the hammond scale, a validated instrument for observer rating of depressive mood (cut-off c ), and a modified version of the had for observer rating (cut-off c ) were used. in addition apache ii, saps ii, sofa, age, sex, comorbidities, reason for admission, length of icu stay and ventilator days were recorded. . by now patients had complete follow up data. of these patients ( %) were classified to have depressive mood at icu admission. in total patients had died by day ( %). the -day mortality was % ( / ) in patients with depressive mood and % ( / ) in patients without (p = . ). patients with and without depressive mood did not differ with respect to age, sex, apache ii, saps ii or sofa score at admission. multiple logistic regression analysis with -day mortality as the dependent variable revealed that prevalent depressive mood at the time of icu admission was an independent risk factor for mortality (table ) . conclusions. pre-existing depressive mood is an independent risk factor for mortality in medical icu patients. introduction. some classical post-icu discharge predictors of death are described, such as age, severity of disease and level of nursing care [ ] . besides these factors, some laboratorial data at icu discharge are potential predictors of post-icu death. objectives. the aim of this study was to investigate whether standard base excess (sbe), ph, lactate, hemoglobin level, creatinine, platelets, leukocytes and albumin at the icu discharge as well as the % decrease on c-reactive protein concentrations (crp [ %) from the day pre-icu discharge to the day of icu discharge may be useful predictors of in-hospital outcome. patients discharged from the icu after at least h of stay were retrieved from our prospective collected data base. a multivariate analysis was performed using a backward-lr binary logistic model taking in-hospital death as a dependent variable and the cited data as independent variables. results. patients were retrieved. the average age was ± years old, mean apache ii score was ± , and the main causes of admission were septic syndromes and respiratory failure. the in-hospital mortality after icu discharge was %. the icu length of stay was ± days. at the time of icu discharge ph was . ± . , sbe was - . ± . mmol/l, lactate was . ± . mmol/l, hemoglobin . ± . , creatinine was . ± . g/dl, albumin was . ± . g/dl, platelets was , ± , /mm , leukocytes was , ± , cells/mm and the number of patients who lowered crp at least % were ( % conclusions. this study demonstrated that sbe, lactate, hemoglobin and albumin concentrations on the day of icu discharge are independent predictors of in-hospital mortality. moreover, the reduction on crp levels above % in the last h of icu stay is a strong predictor of better in-hospital clinical outcome. we suggest that these variables together with the clinical judgment may be taken into account on the icu discharge decision process. readmissions to the intensive care unit (icu) are usually associated with increased morbidity and mortality, and they may evidence the quality of patients' care. the risk for icu readmission varies across studies, and is generally analyzed just before icu discharge, leading to deviation of icu team and patients' daily goals. early prediction may improve the care for patients in risk for icu readmission, and help developing mechanisms for its prevention. objectives. to analyse risk factors for readmission in intensive care unit looking at the first h data after unit admission. methods. the first intensive care unit admission of patients was analyzed from january to december in a medical-surgical unit. readmission to the unit was considered those during the same hospital stay or within months after intensive care unit discharge. deaths during the first admission were excluded. demographic data, acute illness and comorbidity prognostic scores, and use of mechanical ventilation were submitted to uni and multivariate analysis for readmission. numeric variables were expressed as median or percentage. conclusions. age, medical admission, sofa score and respiratory-and/or sepsisrelated admission are early associated with increased icu readmission risk. objectives. the aim of this study was to examine patient perceived hrqol in former icu patients that die in the period from month up to years after discharge from intensive care unit and the hospital. methods. prospective, multicenter study in three mixed icu's in sweden. questionnaires, including hrqol (sf- ), demographic data and previous illnesses, were sent out six, , and months after discharge to all former adult icu patients. data for this study were only collected among those dying before the months post-icu follow-up. of the patients who returned the questionnaires ( . %) died, ( . %) between and months, ( . %) between and months, and ( . %) between and months. the most frequent admission diagnoses were respiratory problems n = ( . %) and gastrointestinal diseases n = ( . %). examining hrqol in the former icu patients the following observations were made: (see fig. ). a pronounced and quantitatively large decrease in hrqol is seen for the surviving patients with pre-existing disease as compare to the previously healthy survivors. although already at a very low value further decreases in hrqol for the patients dying before years post icu is significantly less as compared to the icu patients with pre-existing disease that survives. the decrease is mainly in physical function, role physical function and role emotional function (marked in the figure). conclusions. yes, health related quality of life is extensively affected, mainly in the dimensions physical function, role physical function and role emotional function. importantly, in these two affected physical dimensions a shorter time to death increases such a decrease. the finding further stresses the importance of pre-existing diseases for the final hrqol outcome of former icu patients. introduction. despite initial recovery from critical illness requiring icu admission, many patients remain at risk of subsequent deterioration and death [ ] . recent studies have shown readmission rates ranging between and % [ ] ; this population had mortality rates six times higher and were eleven times more likely to die in hospital [ ] . . to calculate the readmission rate in our mixed icu unit over a months period . to identify risk factors associated with readmission into the icu . to study the outcomes of these readmissions methods. a retrospective observational study, data was collected from an icu computer database (metavision) and analysed manually results. the total number of admissions in this period was , average patient age was ± with . % being males. readmissions constituted . % of the total admissions with . % of those readmitted within h of their initial discharge. % of the initial discharges from the unit were made out of hours i.e. unplanned, presumably due to heavy demand on beds. readmissions were particularly associated with patients discharged to surgical wards . % and the hepatobiliary hdu . %, the latter might reflect the proportion of that particular patients population received. . % of the readmissions required to stay h or less in icu. the overall mortality of the patients requiring more than one admission in this months period was . %. there is an urgent need for expanding icu services in our hospital, i.e. extra beds, staff, outreach teams, etc in addition to investing in nursing capacity building especially in surgical wards. we agree with others studies that compared with the general population, icu survivors report lower hrqol. moreover, a relationship between several factors like sepsis, renal failure, sofa (first and second day score), critical illness polyneuropathy, mechanical ventilation, sedation time, previous psychiatric history and blood products transfusions were found in our study population. conclusions. according to our data, subclavian vein was the most common insertion site used, especially as nd and rd placement and was related with the lower incidence of becteremia episodes. although the risk of placing a cvc for inflection complications is against the risk for mechanical complications, we have to improve our cvc policy, preferring the subclavian or the jugular site of insertion, in order to minimize the infection risk for a nontunneled cvc. objectives. objectives for this study were to determinate the frequency and the risk factors associated with bos. secondarily, we searched several variables as civil status, age, sex, work seniority as potential risk factors. inclusion criteria were to work in critical care unit (ccu) the hospital clínico universidad de chile (hcuch). this unit included subunits: intensive care unit (icu), middle care unit (mcu). the mbi Ò instrument was applied between april to july of . all staff of ccu were asked to response the instrument. as previously reported, bos was defined with high ee, high dp and low pa. risk of bos was anything of the three dimensions positive for bos. we gave information on specifics objectives and the schedule of a future intervention programme. for analysis, comparisons were made based on student t test, chi-square test with yates corrections or fisher exact test as corresponded. for all tests we used confidence interval % with p \ . . a total of mbi Ò tests that included all sub-units in ccu. this is a % of all personal working in the ccu. bos was found in . % of cases. women ( %), unmarried ( %), with an average of age . years old. ( - years old) and with a work seniority younger than years ( %). ee is high ( . %), for nurse and paramedical personals. dp was . and . % to middle level, for nurse and medical doctor, and low pa in % for paramedical personal, with longer work seniority (more than years). risk factors were female gender, unmarried status, childless, middle aged ( - years old) and recent start in the job (stay younger than years). introduction. burnout is a prolonged response to chronic emotional and interpersonal stressors on the job, and is defined by three dimensions: exhaustion, cynism (depersonalization), and inefficacy. icu physicians are exposed to several stress factors and are particularly predisposed to this syndrome. to describe the prevalence of burnout syndrome among intensivists and its relation to their quality of life. methods. an epidemiological cross-sectional survey conducted to evaluate all adult icu physicians in salvador, ba (brazil), from october to december . the quality of life and burnout syndrome were evaluated respectively by the whoqol-bref instrument and the maslach burnout inventory (mbi). burnout was classified into low, moderate and high levels for the three studied dimensions, according the mbi classification, and it was defined by the presence of a high level in at least one dimension. the quality of life was evaluated in four domains: physical, psychological, social relationships and environment, graduated from to , with higher scores denoting higher quality-of-life. [ ] ) has been successfully used to measure nursing workload on an intensive care unit over a -h period. in contrast to intensive care, the nursing care workload on mc is not evenly spread over a twenty four period, but tends to vary between shifts. objectives. the aims of this pilot study were ( ) to assess the fitness of nas as an accurate reflection of nursing workload on an mc unit. ( ) to determine the nursing work load, per patient, per h shift. prior to the commencement of the study all thirty one nurses taking part received instruction in the content and registration of nas. at the end of each h shift, each nurse retrospectively scored their patient(s) using nas. this consists of a check list containing twenty three items giving a possible score between and , where equates to . full time equivalent (fte) intensive care nurse. the nas were entered in to a database and the average scores, per patient, per shift were calculated. three hundred patients were retrospectively scored over a -month period in october and november . not all patients were scored on all three shifts as some patients had been transferred out of the unit before shift end. in addition any incorrectly completed forms were discarded and excluded from the study. methods. this multicenter pilot study included doctors working at (pediatric) intensive care units (icu). subjects were randomly assigned to two groups: one was first tested during day, then during night, while the other was tested in reverse order. the d test of attention [ ] was used to assess attentional performance. total performance (tn-f) score, standardized for age and level of education, was used to express attentional performance. subjective, -to- scores were gathered in two questionnaires. results. figure displays standardized total performance scores of doctors. measured attentional performance showed high intra-and interpersonal variability and did not differ between both shifts (p [ . ). in contrast, doctors expected alertness to be decreased ( . ± . and . ± . (mean ± sd) on subjective -to- scale during day and night shifts, respectively; p \ . ) and the chance of making errors to increase (from . ± . to . ± . (mean ± sd); p \ . ) during night shifts. conclusions. physicians working at icu are aware of the risk of making errors during night shifts. however, we showed that doctors perform equally during night and daytime when confronted with a short-time challenging task. consequently, a discrepancy between measured attentional performance and expected alertness was observed. these results suggest nocturnal alertness might be comparable to daytime during short-lasting tasks that elicit a high level of stress and motivation (e.g. testing, medical emergency). further research is needed to elucidate if longlasting (routine) tasks reflect decreased sustained attention and contribute to medical errors. we studied physicians, the majority of whom were male ( %). mean age and time since graduation were . and years, respectively. high levels of emotional exhaustion, depersonalization, and reduced personal accomplishment were found in . , . , and . %, respectively. prevalence of burnout syndrome, defined as a high score in at least one dimension, was . %, while prevalence was . % for all three dimensions. in conclusion, burnout syndrome was common in this sample of icu physicians. aims. our goal was to assess the physician's opinion about potential competencies of a triage nurse. a representative cross sectional study design was applied with self-fill-in questionnaire about physician's attitude related to skills of triage nurses. the questionnaires were distributed between september and november in (out of ) eds. in this survey physicians' questionnaires were processed. chi-square and student-t test was used for comparison of variables. p values less than . were considered statistically significant. results. . % of physician would support the special training of triage nurse. . % of physician suggests that the nurses use the patient's physical examination regularly in eds. the full time (ft) emergency physician significantly would reduce the basic competencies of nursing (e.g. dressing, feeding of patient, p = . , and p \ . , respectively) than parttime (pt) emergency physicians. significantly greater part of the ft physician would widen the competency of triage nurses in the field of physical examination of nervous system (p \ . ) and cardiovascular system (p = . ) than the pt physician. conclusion. hungarian emergency physician would widen the competency of triage nurse, but only half of physician would like to that nurses apply physical patient examination in practice. the full time physician would give more competencies for triage nurse than part time ones, but the final field of competency will be depended on other factors. healthcare-associated infections (hcai) are estimated to affect . million people worldwide, causing longer hospital stay, increasing hospital costs and excess mortality [ ] . hand hygiene represents the single most effective way to prevent healthcareassociated infections. compliance with hand hygiene amongst healthcare workers (hcw) has been demonstrated to be quite low at % [ ] . to quantify the degree of compliance to hand hygiene norms in the icu and to assess the short term success of strategies to improve hand hygiene compliance. setting. bedded medical-surgical icu in a tertiary care centre. design. prospective observational. method. unobtrusive observer (single person). observed over sessions of h. the compliance was calculated as :number of times the staff performed hand hygiene/number of hand hygiene opportunities. the number of hand hygiene opportunities was based on the who tools [ ] : before touching a patient, before clean/aseptic procedures, after body fluid exposure risk, after touching a patient and after touching patient surroundings. introduction. icu delirium represents a form of brain dysfunction that in many cohorts has been diagnosed in - % of patients receiving mechanical ventilation. delirium is a common but complex clinical syndrome characterized by disturbed consciousness, cognitive function or perception, which has an acute onset and fluctuating course and is associated with poor outcomes. and yet, it can be diagnosed and treated. in the uk, reporting of delirium is generally considered to be poor. in light of updated nice guidelines on delirium due out this year, specialist clinical assessment will soon become gold standard as a means of diagnosing and reducing the prevalence of this condition in the icu setting. nice recommends that cam-icu (confusion assessment method) be used by healthcare professionals who are trained and competent in the diagnosis of delirium. on our -bed unit, we are currently implementing cam-icu assessments to be performed twice daily (at the commencement of each nursing shift) as well as rass (richmond agitation and sedation scale) scoring on an hourly basis for all patients. objectives. to implement training of all our icu nursing staff in the use of cam-icu and rass scoring. to periodically validate and reinforce earlier training, so as to improve assessment and reporting of delirium. methods. our 'delirium group' comprising both nursing and medical staff, taught cam-icu and rass to staff members using multimedia presentations in small groups and/or individual teaching sessions over weeks. scoringofcam-icu andrasswassubsequentlyauditedon occasions post training. discrepancies were discussed and post-audit retraining provided where necessary. results. the following audit and validation data were generated on our unit as documented in table . no statistical analysis was undertaken. we anticipate focusing on the challenges encountered and strategies used in managing this change in our icu practice. methods. the factors causing resistance to change based on multisource data. qualitative technical methods were used: brainstorming and focal groups. the data collection elaboration was created by the collaboration of icu nurse, quality department nurse and external reviewers. finally, the main factors were classified in different categories. each category was scored by to according to gravity and prevention possibility. finally, priority was given to more serious and easier prevention problems. results. the most serious problems for icu professional was the historical factors. the easier solution problems were ''the lack of information'' and all evaluators were agree with it. we arranged the factors in order to the next classification (tables and ). discussion. all investigators were agreed with the low importance of problems with payments and low prevention probability of low organisational flexibility, so they were agreed on not to work about them. the icu professionals were more pessimistic and have lower confidence in prevention possibilities but they showed more confidence about the capacity to learn new skills. they weren't worried about resistance to do experimental things. probably, historic factors play an important role in this pessimistic attitude. on the other side, quality and safety experts have more experience in prevention programs and they put all their trust in its. after doing the analysis, we chose the ''lack of information problem'' to plan prevention activities. we consider it is a serious and real problem but at the same time, easy of prevent. conclusions. the implementation of the patient safety program in the icu means a real cultural change. the priority analysis could help to plan strategies in order to avoid the program failure. objectives. we concerned about whether medical personnel could recognize management of the cuff of artificial airway or not. we asked to doctors and nurses working in intensive care unit of konyang university hospital, daejeon, republic of korea. we asked questions with contents of questionnaire that was composed of methods of set initially, maintenance and appropriate pressure of cuff. results. of medical personnel replied to us. most of them had worked in intensive care unit, so they had placed of artificial airway. . % of them used manometer to adjust the cuff. we could find that nurses had more cognition compared to doctors for it ( vs. %). only . % of doctors described pressure of the cuff in medical record. of medical personnel replied that they knew the appropriate range of cuff pressure. % ( / ) of them replied that the range of cuff pressure was kept with - mmhg and % ( / ) was - mmhg. % of nurses in the icu knew that range of cuff pressure was - mmhg. most of them knew complications of high and low pressure of the cuff. . % of medical personnel monitored the cuff balloon during receiving mechanical ventilation and they used manometer to adjust it. % of nurses knew that the cuff should be adjusted continuously, but % of doctors did. interval measuring the cuff pressure was % of once a day, % of three times a day, % of more than four times a day conclusions. most of the medical personnel knew to keep appropriate cuff balloon to prevent various complications of artificial airway. they had insufficient cognition about maintaining the cuff balloon and appropriate level of cuff pressure. that was more prominent in doctors than nurses interhospital transfer is occasionally required as a consequence of limited therapeutic options or because of a need for a higher intensity of medical care that cannot be given in rural intensive care units. along with the potential benefit for the to be transferred patient, transport may also lead to hemodynamic and pulmonary deterioration. in order to minimize additional risk of interhospital transport of critically ill patients, a mobile intensive care unit with a specialized retrieval team was established in our university hospital-based intensive care unit. from march , transport of the critically ill patients in our adherence region are performed by micu. objectives. in this prospective audit adverse events and patient stability during micu transfers were assessed and compared to our previous data on transfers performed by standard ambulance [ ] . results. interhospital transfers over a -month period were evaluated. systolic blood pressure, glucose and haemoglobin were significantly different at arrival compared to departure, although never significant values for major deterioration were reached. an increase of total number of variables beyond threshold at arrival was found in % of patients, percent exhibited a decrease of one or more variables beyond threshold and thirty percent showed an equal number of trespassed thresholds. there was no correlation between the patients status at arrival and the duration of transfer or severity of disease. icu mortality was %. compared to standard ambulance transfers of icu patients performed in , there were far less adverse events: . vs. %, which in the current study were merely caused by technical (and not medical) problems. although mean apache ii score was significantly higher, patients transferred by micu showed less deterioration in pulmonary parameters during transfer than patients transferred by standard ambulance. conclusion. transfer by micu imposes less risk to critically ill patients compared to transfer performed by standard ambulance and has therefore resulted in an improvement of quality of interhospital transport of icu patients. introduction. previous studies in adult intensive care units (icus) reported rates of pre-mortem to post-mortem discrepancies ranging between and % depending on the population studied. and, most of them were retrospective studies, which included small number of patients. to compare clinical and pathological diagnoses and to determine the types of errors in a large and multidisciplinary icu-patient population. we conducted a prospective study of all consecutive autopsies performed on patients who died in the icu of the hospital universitario de getafe, madrid, spain, between january and december . the diagnostic errors were classified in two categories: class i errors that were major misdiagnoses with direct impact on therapy, and class ii diagnostic errors which comprised major unexpected findings that probably would not have changed therapy. conclusions. this study found significant discrepancies between clinical diagnoses before death and post-mortem findings. this reinforces the importance of the post-mortem examination in detecting otherwise unexpected diagnoses and improving the quality of care of critically ill patients. introduction. unplanned extubation is associated to a high risk of reintubation end correlates with increased risk of nosocomial pneumonia. on the other hand, reintubation significantly increases morbidity and mortality in critical ill patients, increasing the incidence of ventilator associated pneumonia (vap) rate and makes the airway management risky. objectives. the aim of our study was to test the rate of unplanned extubation as well as the reintubation rate in our icu, in order to evaluate the efficiency of our airway and weaning time protocols. methods. during a nearly year's period, patients admitted to the icu, mean age: . years, mean apache ii score: . , mean los: . days, with predicted and actual mortality: . and . % respectively. from these, were intubated and included retrospectively in our study. patients were extubated, while the others either underwent bedside percutaneous tracheostomy or died. we concerned that the number of days of mechanical ventilation were about equal to the number of days of intubation. reintubation was defined as the need to reintubate during the first h after extubation. we recorded four episodes of unplanned extubation. three of them caused by malfunction of the tube due to secretions and airway obstruction and one of them was undesired extubation caused by the patient himself. the total number of days of intubation was , , mean ± sd: . ± . , min: , max: days. therefore the rate of unplanned extubation was . %, while the standard limit is below %. the total number of reintubations was , while the total number of scheduled extubations was . therefore, the reintubation rate was . %, while the standard limit is below %. conclusions.the recorded rate of unplanned extubation was low in our icu patients, below the acceptable limit, assuming that our sedation and airway management policy is effective. on the other hand, the recorded rate of reintubation was high in our study, above the acceptable limit. although a low rate of reintubation might indicate excessively long mechanical ventilation times, this did not recorded to our study. nevertheless, our data suggest that we have to improve further our weaning time protocols, making the extubation procedure safer, and avoiding risk factors for vap. . pvs such as inappropriate enrollment of patients with a contraindication to the study treatment may lead to excess harm in the active intervention group [ ] and failure to deliver the study intervention according to the study protocol may underestimate true treatment efficacy [ ] . full reporting of pvs may aid in the interpretation of rct results however there are no published reviews on this topic [ ] . objectives. to determine reporting rates for key types of pvs and to investigate study characteristics that may be related to reporting. publications were excluded because they were subgroup or economic analyses of a previously published rct [ ] , not a rct [ ] , not published in the target journal [ ] , systematic reviews [ ] , or other reason [ ] . median trial size was participants (range: to , ). / ( %) of rcts were single centre, / ( %) were industry funded and / ( %) reported negative findings. overall / ( %) of rcts reported some form of pv, these included: / ( %) patient compliance; / ( %) discontinuation of study intervention due to safety; / ( %) study intervention-related researcher error; / ( %) inappropriate enrollment and; / ( %) technical errors in randomisation. multi-centre rcts may be more likely to report study intervention-related researcher errors ( % of multi-centre trials vs. % of single centre trials, p = . ). academic trials were less likely to report discontinuation of study intervention due to patient safety ( % of academic trials vs. % of industry trials, p = . ) and were less likely to report technical errors in randomization ( % of academic trials vs. % of industry trials, p = . ). conclusions. multi-centre trials are accepted to be organizationally complex. on-site education may be required to reduce errors in study intervention delivery attributable to the research team. it is possible the apparent excess harm attributable to industry trials is a reporting artifact however, if it is real, it must be addressed. additional research is required to investigate patient safety-related pvs and technical randomization errors, which may be lower in academic trials. to determine the occurrence of harmless incidents and ae related to physician's competences in icus, disclosing their potential risk factors. conclusions. this prospective study was essential to identify the proportion of our icu admissions affected by md-inc and md-ae, disclosing their nature. our md-ae rates, affecting more than % of admissions, were higher than those described in prior general studies, including not only icus. among the detected md-ae, hypoglycemic episodes not related to insulin administration predominated, indicating important deficiencies regarding nutritional support. severity on admission and length of stay were important risk factors for the occurrence of at least one md-ae. a systematic measurement and analysis of unintended events (ue) have been recommended for patient safety and improvement of quality of care in critically ill patients. however, a spontaneous reporting system may be inefficacious in intensive care unit (icu) because of a poor data collection, particularly by physicians staff. objectives. the aim of this study was to evaluate the reliability of a staff spontaneous event report by comparison with events collected by an external observer in a surgical intensive care unit (icu). to facilitate the reporting and the analysis, we identified a series of events with a serial number and a colour code related to their for each of the following macro-phases: icu bed booking, admission procedures, patient stay, discharge and emergency procedures. a specific structured form including ue's code and colour, date and hour of the event and type of patient has been prepared and proposed to staff -week for each month after a proper phase of education. the report was voluntary and anonymous and the data collected during the morning shift from september to december have been compared to those collected from an external observer. in the studied period, healthcare staff reported ues: % collected by nurses, % occurred during the morning shifts and % were classified as moderate or severe. the rate of ue in the morning shift was ues per patient days. the external observer identified events in morning shifts with an incidence of ues per patient days. the violation of isolation rules for patient with multi-drug resistant bacteria infection both by icu staff and surgical consultant was the ue observed more frequently by the staff ( %) and by the external observer ( %). conclusions. the above data indicated that: . in our icu the incidence of ue is very high, particularly for compliance to isolation of infected patients and . the spontaneous reporting system under-estimated largely the real incidence of ues. introduction. importance of renal assessing in intensive care unit (icu) patients is unquestionable for a correct drug dosing, fluid requirements or decisions for renal replacement therapies. serum creatinine (sc) is a very common biochemical parameter in clinical practice for assessment of renal function. many equations have been designed to estimate creatinine clearance based on sc, but their capacities for providing a correct estimate of glomerular filtration rate (gfr) are suboptimal. this is even worse in critically ill patients due to malnutrition and/or immobilization. in clinical practice, despite its limitations, h-urine creatinine clearance (crcl h ) is used as a reference method to determine gfr. data show that cystatin-c could be promising as an endogenous filtration marker in icu settings. objectives. to assess in a medical icu population whether the arnal-dade formula of cystatin-c clearance (cc) developed from serum cystatin-c (scc) shows better predictive performance of gfr than sc-based formulae, as regards to patients' renal function: crcl h c ml/min . m or crcl h \ ml/min . m . results. all formulae showed notable bias from the reference method. interestingly, all equations based on sc-values clearly overestimated crcl h (cg: . %; mdrd: . %; fv-mdrd: . %), whereas cc showed underestimation of these crcl h (cc: - . %). in the crcl h c ml/min . m group (n c = ; patients), cc showed the best correlation indexes (cc-crcl h ; r = . , r = . ), the second most biased (- . %) and the worst precision ( . %). in this group, mdrd was the least biased (- . %) and the most precise ( . %). in the crcl h \ ml/min . m group (n \ = ; patients), cc was the worst correlated with crcl h (r = . , r = . ), in contrast to mdrd (r = . , r = . ). in terms of precision, mdrd showed again better results than cc: . % vs. . %, respectively. conclusions. in our icu population, cc did not demonstrate a clear improvement on the remainder sc-based formulae in either of the two groups according to crcl h . however, in a patient with high mdrd values and suspicion of low gfr, cc could be useful as guidance before obtaining the definitive confirmation by crcl h . introduction. there are well established and robust techniques for measuring and categorizing renal function in people with chronic kidney disease (ckd). a number of rapid bedside estimates of renal function have been devised incorporating routine daily measurements, such as serum creatinine, in combination with demographic data (e.g. cockroft-gault, the mdrd series). the addition of serum cystatin c measurements to some equations may also improve accuracy of estimation. the current and accepted categorical classification of acute kidney injury (aki: akin/rifle) has been useful epidemiologically but does not provide a continuously variable measure of severity of aki which would be valuable for both clinical management and research. objectives. previously published abstracts have suggested a role for egfr in describing renal function in the critically ill but a more comprehensive analysis was needed. methods. ( male) (mean age range - ) critically ill patients with aki were recruited. a h creatinine clearance ( crcl) (previously validated as a measure of renal function in critically ill patients) was measured and simultaneous blood sampling was done for creatinine, urea, albumin and cystatin c. various equations used to estimate gfr were compared to crcl with regression and bland-altman analysis. all patients had a crcl of\ ml min per . m introduction. epithelial-mesenchymal transition (emt), a key process in tissue development and repair, has also been identified as a major mechanism in fibrogenesis. the cytokine tgfb has been shown to induce transformation of epithelial cells into matrixforming and smooth muscle actin (sma)-expressing myofibroblast (mf) via emt. the other prerequisite is an injury-induced loss of intercellular contact, including adherens junctions (ajs). the classical experimental method to induce aj disruption is the uncoupling of e-cadherin-mediated contacts by low calcium medium (lcm). this concept has been termed as the two-hit model of emt ( ). b-catenin, a scaffold protein of the aj, released by cell contact injury, can act as a transcription factor and has been shown to facilitate emt. however, the mechanism whereby cell contact injury promotes emt is not understood. our recent studies have shown that smad , one of the main signal transducers of the tgfb pathway is a strong inhibitor of epithelial sma expression, by interfering with myocardinrelated transcription factor (mrtf) [ ] . the latter is the main driver of the sma promoter, through it association with serum response factor (srf). intriguingly, b-catenin can bind to smad . to clarify the mechanisms whereby aj injury promotes sma expression. methods. ajs were manipulated in kidney tubular cells, either by sirna-mediated downregulation of e-cadherin, b-catenin or through chemical uncoupling of ajs by lcm. protein expression was detected by western blotting and immunofluorescence microscopy, proteinprotein interactions were monitored by co-immunoprecipitation, and the activity of the sma promoter was determined by luciferase reporter assays. knockdown of e-cadherin promoted b-catenin translocation to the nucleus and induced a threefold rise in the tgfb-triggered sma expression. conversely, silencing of b-catenin strongly suppressed the two-hit (tgfb + lcm)-induced activation of the sma promoter, and inhibited sma protein and mrna expression by %. the same stimuli induced strong association of b-catenin with smad . transfection of cells with a b-catenin expression vector dose-dependently prevented the inhibitory action of smad on the mrtfinduced activation of sma promoter. moreover the active (myogenic) mrtf-srf complex was restored, as b-catenin preempted smad 's inhibitory effect on the complex. these studies define a novel mechanism whereby epithelial injury activates the myogenic program, a central process in organ fibrosis. our results imply that b-catenin, liberated from the injured ajs, facilitates the activation of the myogenic program by preventing or mitigating the inhibitory action of smad on mrtf. these hitherto unknown interactions among smad , b-catenin and mrtf represent novel targets to lessen fibrogenesis. introduction. in intensive care unit (icu) patients, kidney function is monitored by the creatinine clearance (crcl). it can be measured by two methods. urinary crcl (ucrcl) is directly measured, using the urinary and serum creatinine. but commonly crcl is estimated from serum creatinine (scr) alone, as estimated glomerular filtration rate (egfr); using equations validated in chronic kidney diseases. there is paucity of literature on validation and comparison of these methods in icu (hoste) . objectives. we compared -h timed ucrcl and egfr in the newly admitted critically ill. we also sought to ascertain the incidence of high crcl and the agreement between methods in this subgroup. conclusion. the use of rifle criteria gives a high incidence of aki in the icu setting. in this unselected population of critically ill pts, cysc seems to be superior to cre in predicting pts who will develop aki and will need rrt during their hospitalization in the icu. early identification of high risk patients may allow potentially beneficial therapies to be initiated early in the disease process, before irreversible injury occurs. introduction. the contrast-induced nephropathy (cin) is consider to be the most frecuence reason of acute renal failure in hospitalized patients. they are defined by a fixed increase ( . mg/dl) o a % rise serum creatinine level after to be exposed h to the contrast. the main complications are kidney and cardiac problems and this will lead to longer hospitalization and increased mortality. objectives. to compare cin occurrence after a injecting a iso-osmolar contrast (ioc, idixanol) or a low-osmolar contrast (loc, iohexol) to a group of patients submitted to coronary angiography, with o without percutaneous coronary intervention (pci). to establish unrelated cin markers and to evaluate the efficiency of the kidney protection protocol used in our hospital. conclusions. the loc was associated to a greater number of cin than ioc. patients who developed cin were significantly longer hospitalized. the use of point giving system that includes cin's predictors like dm, hematocrit \ %, ami, and treatment with diuretics helps us to classify cin risk and use a correct kidney protection protocol. introduction. the incidence of acute renal failure in the intensive care unit (icu) is around % of cases and is related to increase in mortality in patients who required dialysis as far as %. early detection of acute kidney injury (aki), after damage is not on set could be crucial to develop therapeutic strategies to modify the course of injury. blood and urinary concentrations of ngal are early biomarkers of aki ; to date, little information exists regarding ngal usefulness in critically ill patients. objectives. to analyze: . the capacity of urine ngal (ungal) to predict akievaluated by rifle score-in critically ill patients and, . the ungal values in patients with sirs, sepsis or septic shock. methods. ngal was measured in urine sample by an automatic analyzer device (architect ci Ò ; abbott diagnostics) at admission and h later in patients admitted to a general icu. patients were classified both by rifle score at admission and and h later and by ungal concentrations at admission. to the later classification, the cut-point for aki prediction was obtained by roc curve analysis. ungal values at admission were compared in patients with sirs, severe sepsis or septic shock. clinicians were blinded to ngal results. the study included consecutively-admitted patients ( female) with mean age . ± . years, and length of icu stay of . ± days. fifty-four sirs, severe sepsis and septic shock. thirteen patients developed rifle f score, of them at icu admission; extracorporeal renal therapies were required in cases. when patients were classified according to their rifle score at h of admission, ungal values at admission were: ( - ) ng/ml in patients with rifle , ( - ) ng/ml in with rifle r, ( - ) ng/ml in with rifle i and ( - ) ng/ml in with rifle f (p = . ). five patients were excluded, three died before h with ungal ( - , ) ng/ml and two were discharged before h with ungal ( - ) ng/ml. the area under roc curve of ungal at admission for aki prediction was . ( % confidence interval . - . , p \ . ), with an optimal cutoff value of ng/ml with % sensitivity and % specificity. forty-seven patients have ungal b ng/ml. ungal concentrations at admission were ( - ) ng/ml in patients with sirs, ( - ) ng/ml in patients with severe sepsis and ( - ) ng/ml in patients with septic shock (p = . ). conclusions. urine ngal concentrations measured at icu admission appeared as a useful predictor of aki in critically ill patients; in addition, ungal concentrations showed an increasing pattern from sirs to severe sepsis and septic shock. rd esicm annual congress -barcelona, spain - - october s introduction. two previous studies using the rifle criteria in intensive care patients have found the incidence of acute kidney injury (aki) to be and %. however, these studies used calculated basal value of creatinine in a considerable proportion of their patients, which is a possible source of error. objectives. the aim of this study was to investigate the incidence and severity of acute kidney injury in intensive care patients using true baseline creatinine values. objectives. the aim of this study was to define the status of hcy and b vitamins at admission and days of icu stay in critically ill patients, and to evaluate its relationship between them. a prospective study was done on critically ill consecutive patients with inclusion criteria: c years old, sirs and apache ii [ . hcy, b and folic plasma levels were measured by enzymoimmunoassay and enzymatic method. for b , b and b in erythrocyte. permission was obtained from an institutional ethical committee and written informed consent was asked. results. at and days of icu stay and % of patients were b deficient, respectively. and % were b deficient on both times, respectively. folic levels show significant differences between and days of icu stay. we found association between b vitamin and hcy at admission and days. no differences were found between and days hcy values. introduction. cytochrome p a (cyp a), the most abundantly expressed cytochrome p enzymes in liver, are responsible for the metabolism of over % of drugs used across several therapeutic classes. in adults, cyp a is represented primarily by the major isoform, cyp a , and a polymorphically expressed isoform, cyp a . individuals with at least one wild-type cyp a * allele synthesise functionally active enzyme while homozygotes for the * allele are functional non-expressers of the enzyme. the presence of functional cyp a increases the hepatic metabolism of cyp a substrates such as tacrolimus. ckd is known to reduce the hepatic metabolism of drugs via the cyp a enzyme system and we have shown, recently, that aki has a similar effect and that the length of time with aki is the most important variable. we hypothesise that expression of functional cyp a may reduce the impact of aki on hepatic drug metabolism as has been shown to be the case for drug interactions with the imidazole antifungals. methods. ( male) (mean age range - ) critically ill patients with no aki and varying degrees of severity of aki were recruited. midazolam concentration was measured h after intravenous administration as a probe-drug for hepatic cyp a / enzyme activity (t [midazolam] ). this is a validated method for testing cyp a activity in critically ill patients. patients were excluded if they were on any known cyp a / inhibitors. results. two patients with severe aki had unexpectedly high t [midazolam] . figure demonstrates the following: without a cyp a * allele, the rate of midazolam metabolism increased with duration of aki (r = . ; p \ . ) (solid line). patients who had at least one * allele (dashed line) were protected from the inhibitory effect that aki has on hepatic drug metabolism (significant difference between the correlation lines p = . ). if the two major outliers are removed (dotted grey line) from the * /* group (r = . ; p \ . ), the correlation lines remain statistically different (p = . ). conclusions. the presence of an allele which codes for functional cyp a protects critically ill patients from the inhibitory effect of aki on the hepatic metabolism of midazolam. thyroxine replacement therapy has become commonplace in the management of organ donors to reverse hemodynamic instability and homeostasis, yet the pharmacokinetics of thyroxine are unknown in this patient population [ , ] . since t is only available in oral form, we studied the pharmacokinetics of oral versus intravenous t to determine if oral administration is suitable. objectives. ( ) to study the pharmacokinetics of oral versus iv t therapy; ( ) to determine if oral thryoxine therapy is suitable. with ethics approval and signed consent from the substitute decision maker, patients who were determined to be neurologically dead and consented for organ donation, were randomized to receive either an oral or intravenous dose of t ( mcg/kg). all patients received an oral and iv preparation; one of which was a placebo. this study was also double blinded and randomization occurred in blocks of - . free serum levels of t and t were measured hourly until the time of organ procurement. the area under the curves (auc) were determined and compared using. results. there were patients ( males) in the oral versus patients ( males) in the iv group, with an average age of ± vs. ± , respectively. there was no significant difference at baseline or h between groups for hemodynamic variables, free t , free t or tsh levels. the only exception was map where it was higher at baseline in the oral group and there was a significant increase at h in the iv but not the oral group ( - vs. - in the oral). the auc for t was greater for the iv group ( pmol/l/ h) compared to the oral group ( pmol/l/ h). there was no statistically significant difference in any of the levels from to h between the oral and iv groups. oral bioavailability of t was %. conclusions. administration of iv t resulted in a slightly greater auc compared to oral administration. however, oral bioavailability of t in our population was very high, at %. t is currently the recommended thyroid replacement in neurologically dead organ donors. however, intravenous t is unavailable in many jurisdictions. iv t has been used as a substitute. our study shows that in this select population, oral bioavailability is high suggesting that oral t may be a reasonable alternative. further work is needed to determine whether there was a difference in the number and rate of organ retrieval in the oral versus intravenous groups. introduction. specific characteristics of metabolic derangements occurring in critical illness is domination of developing catabolic state particularly in acute necrotizing pancreatitis. as a result, we faced such a problem as developing a clinically apparent protein-calorie deficiency which is resistant to standard nutritional support. the treatment of acute necrotizing pancreatitis in chronic abuse patients is difficult to handle for the clinician and should include sufficient energoplastic supply. objectives. in our research we aimed to assess the efficacy of adding of ornithineaspartate complex in carbohydrate metabolism in chronic abuse patients with acute necrotizing pancreatitis. methods. comparable chronic abuse patients with acute necrotizing pancreatitis (control group n = , mean age . ± . ; ornithine group n = , mean age . ± . ) received early parenteral nutrition from the moment of admission to hospital with universal system ''three-in-one''. ornithine group also received ornithine-aspartate complex by parenteral administration ( g/day). on the second day the patients were admitted parenteral nutrition and tube feeding h/day. the volume of parenteral nutrition was gradually decreasing. biochemical and metabolic endpoints were measured at baseline and on th day (nitrogen balance, amino acids spectrum, plasma whole protein, transferring concentrations, glucose and insulin levels) at the clinical laboratory in all patients metabolic disturbances with protein status and carbohydrate metabolism shifts were revealed. dynamic of the whole protein, albumin/protein ratio and nitrous balance in both group showed similar tendency of metabolic improvement. dynamic of essential and nonessential amino acids concentration remained normal showing adequate energoplastic supply in both groups. glutamine concentration in ornithine group remained stable and even increased by the th day of nutritional support, while in control group glutamine concentration was decreasing, and by the th day of nutritional support it was below normal values. in ornithine group higher levels of endogenous insulin at normal values of glucose and faster fisher index improvement were detected. conclusions. administration ornithine-aspartate complex in therapy of acute necrotizing pancreatitis in chronic abuse patients, probably, may influence on disease outcome. in ornithine group duration of delirium tremens causes was ± days versus control group ( ± days). restoration of metabolic activities confirms adequate nutritional support in both groups but ornithine-aspartate complex adding provides faster improvement of protein and carbohydrate metabolism. objectives. this study was designed to evaluate the nutrition indexes including serum prealbumin level as prognostic indicators of patient recovery in critically ill patients with comparing severity scoring systems. we selected patients over years old, supplied with total parenteral nutrition (tpn) for more than days in surgical intensive care unit, ajou university hospital, suwon, korea. the serum prealbumin, albumin levels and total lymphocyte count were measured at the first, rd, , , , th days of nutrition support care by tpn. we checked apache (acute physiology and chronic health evaluation) ii score, saps (simplified acute physiology score), mods (multiple organ dysfunction score) and sofa (sequential organ failure assessment) score of patients. results. there were male patients and female patients with mean age . years. the mean day of sicu staying was . days. we compared two groups; survivor group (n = ) and non-survivor group (n = ). there were significant statistical differences in icu staying days (p = . ), apache ii score (p \ . ), saps (p \ . ), mods (p = . ) and sofa score (p = . ) between two groups. however, serum prealbumin level (p = . ), albumin level (p = . ) and total lymphocyte level (p = . ) did not showed significant difference between two groups. receiver operating characteristic curve showed low accuracy of serum prealbumin level as a prognostic factor (area = . ). prealbumin level showed correlation with albumin (r = . ), however did not show correlation with apache ii (r = - . ), saps (r = - . ), sofa (r = - . ) and mods (r = - . ). conclusions. nutrition indexes including prealbumin did not correlated with clinical outcome of critically ill patients. introduction. physical function is impaired following critical illness [ ] . anaemia is a common complication of critical illness and has the potential to influence physical function [ ] . it is not known whether anaemia affects the physical components of quality of life, the ability to carry out the activities of daily living (aodl) or the actual physical function of patients during recovery from critical illness. to determine the physical quality of life, ability to perform activities of daily living and actual physical function in a cohort of icu survivors dichotomised on the presence of anaemia at months following icu discharge. one other organ failure were recruited from a general icu population. patients with a preexisting haematological condition were excluded. baseline and characteristics of icu stay were recorded. the patients were assessed with the sf- quality of life questionnaire (pcs), the frenchay activities index (fai) of aodl recalled for pre-morbid status and at and months, and the min walk test ( mwt) for actual physical function at and months following discharge from icu. organotopic measures of haemaglobin, creatinine, serum c-reactive protein and albumin concentration were also recorded. the results were dichotomised on the presence of anaemia at months for statistical analysis. baseline characteristics were compared with student's t test. a way anova was performed on the pcs and fai score as well as comparisons with t test between each time-point. the distance walked as part of the mwt was compared with mann-whitney u test. patients who remained anaemic at months were older, had a longer icu stay and had a greater requirement for inotropes during their icu stay. the pcs score of quality of life and the fai score was significantly impaired in both groups during follow up, but there was no effect of anaemia. the results of the t tests showed that there was a significant difference between the groups at months for pcs but not for fai scores. the distances walked were severely impaired compared to the normal population ( and m at and months for anaemic group and and m for non-anaemic) in both groups was not significantly different between the two groups. the non-anaemic group did increase the distance walked significantly from to months. there was no difference between albumin, crp and creatinine concentrations between the groups. methods. this experiment was divided into two procedures. the first procedure is to choose two kinds of cell strains, including jurkat cell strain (comes from leukemia) and ccrf-cem cell strain (comes from acute lymphocyte leukemia).we cultivate this two kinds of cell strains to mature stage, then inoculate every kind of cell strain into four culture dishes, two culture dishes was stimulated by lg/ml lipopolysaccharide(study group), and the other two culture dishes serve as blank control(not stimulated by lg/ml lipopolysaccharide). eight hours later, we extracted the microrna in each culture dish. the second procedure is to use the technique of gene microarray to analysis the difference expressions of microrna. in the context of a high altitude expedition human subjects can safely be submitted to prolonged hypoxia and the resulting changes in mitochondrial function can be explored in a controlled fashion. the effect of hypoxia on immune cells-key players in the pathophysiology of sepsis-is of particular interest. to measure mitochondrial function of monocytes during prolonged hypobaric hypoxia. methods. serial blood samples were collected and oxygen saturation was measured in twelve climbers before and throughout a high altitude climbing expedition to pik lenin ( , m). measurements were performed at m (baseline) and at the altitudes of , m (day ), m (day ) and , m (day ) above sea level. pure monocytes were isolated by the use of an antibody-antigen mediated immunomagnetic cell isolation procedure and lysed for determination of activities of mitochondrial enzymes cytochrome c oxidase and citrate synthase. repeated measurements anova followed by least significant difference (lsd) post hoc test were used to compare results on different altitudes. mean oxygen saturation was ± % on , m, and decreased to ± % on , m and ± % on , m (p = . ). we observed an increase in citrate synthase activity on all altitudes compared to baseline levels (p = . ). compared to the baseline, prolonged hypobaric hypoxia induced an increase in the mitochondrial respiratory chain enzyme cytochrome c oxidase enzymatic activity only at , m (p = . ). normalization of cytochrome c oxidase enzymatic activity by citrate synthase activity (relative enzymatic activity) yielded a decrease in relative cytochrome c oxidase enzymatic activity during hypoxia on , and , m (fig. ) . expressing cytochrome c oxidase enzymatic activities as a ratio to citrate synthase is intended to act as a safeguard for potential differences in mitochondrial enrichment. conclusions. the data demonstrates that prolonged hypobaric hypoxia leads to a decrease in relative cytochrome c oxidase activity. this is due to an increase in citrate synthase activity as a marker enzyme for the mitochondrial matrix representing mass and/or number of mitochondria which is not counterbalanced by a corresponding increase of cytochrome c oxidase activity. results. glycocalyx degradation was increased in the lps-treated animals ( . lm, p \ . ) compared to controls. intracellular tissue no concentrations were two-to threefold higher in the lps-treated mice compared to controls (liver, kidney, heart, gut). the number of infiltrating mpo-positive cells increased significantly during endotoxemia. levels of both plasma arg and cit were significantly lower in lps-challenged mice than in controls, whereas plasma ornithine levels were significantly higher. conclusions. in this new developed murine sepsis model, the prolonged infusion of lps resulted in increased glycocalyx degradation and associate endothelial leakage. the enhanced no levels correlated with decreased plasma levels of arg and cit. our murine model with prolonged infusion appears applicable as a model for the human clinical situation, enabling adequate investigation of the influences of the arg-no metabolism on endothelial dysfunction in sepsis. critical illness polyneuromyopathy is a muscular weakness occurring in intensive care unit. one of the major risk factor is sepsis. an early decrease in membrane excitability was described [ ] but corresponding mechanisms are imperfectly known. tnfa is released in the first time of sepsis and could be involved in the physiopathology. objectives. the aim of our study was to investigate tnfa effects on muscular voltage gated sodium channels (nav) in an in vitro model. early effects of tnfa on nav were analysed by macro-patch clamp on muscular fibers isolated from rat peroneus longus. measurements were performed on control fibers and after addition of tnfa at concentrations ranging from . to ng.ml - . the effects of chelerythrine, a specific inhibitor of protein-kinase c (pkc), were also tested. experimentations were realised in a laboratory with permission of experimental research on animals and under the supervision of an authorized person (no - ). tnfa produced a concentration-dependant inhibition of nav currents (fig. ) . maximal inhibition ( % of control current) was observed with concentrations from ng ml - and above. this decrease was fast: % of maximum inhibition was observed in less than min. moreover, chelerythrine inhibited tnfa action on nav. conclusions. in our experimental model, tnfa induce a rapid and concentration dependant decrease of muscular nav currents like observed in chronic sepsis [ ] . as this effect is too quick to be a transcriptional one, and as it is blocked by chelerythrine, it can be assumed that tnfa action is mediated by a nav phosphorylation secondary to pkc activation. in conclusion we evidenced that tnfa reduce muscle excitability in the early stages of sepsis. further studies are needed to obtain a precise description of tnfa mechanisms. may also contribute to cell signaling and regulation of the immune response. nad(p)h oxidase in leukocytes and the vascular wall is a major regulated source of o . we hypothesized that mice deficient in the p phox (ko) component of nad(p)h oxidase would have less pulmonary inflammation than wild type (wt). we treated wt or ko mice with iv saline or lps and assessed lung injury by: . wet-dry-weight ratio; . leak of evans blue (eb) labeled albumin; and . histological score for edema. we used myeloperoxidase activity to indicate neutrophil (pmn) accumulation in lungs, and measured accumulation of macrophages and neutrophils in bronchial alveolar lavage (bal). apoptosis was assessed by tunnel staining. we also expression of icam- , an adhesion molecule, and nitric oxide synthase (nos) enzymes, enos and inos (western and northern analysis) as well as nitrotyrosine formation. results. lung injury was increased in both groups. surprisingly there was greater eb leak in ko than wt at h and a greater edema score at and h. pmn and macrophage accumulation in bal were the same in both groups at h but greater in ko mice at h. myeloperoxidase activity was similar at h post lps in ko and wt indicating that similar accumulation of pmn in the lungs. apoptosis was increased in both groups at h, but resolved in wt at h and persisted in ko. nitrotyrosine was increased in both groups but appeared higher in ko. expression of enos and inos increased in both groups but was greater in ko than wt. conclusions. in contrast to our prediction, lung injury was greater in p phox ko mice which indicates that this complex is not essential for lung injury. however, the injury was more severe and prolonged in ko mice indicating that o may regulate the inflammatory response. introduction. septic shock remains the main cause of mortality in the icu, thus a persistent challenge. recently, dna and mrna analysis by microchip and gene expression by real time pcr highlighted proteins s a , s a and their complex, known as the calgranulins, as potential key prognostic markers for this disease: those two proteins, whose expression seems to be restrained to phagocytes cells are newly recognized components in sepsis-induced inflammation. moreover, they were shown to be at significantly higher concentrations in the plasma of septic shock patients that were going to die. in the contrary, those who were to survive saw their plasmatic concentration decrease, all severity scores in between the population being the same. objectives. the aim of this study was to determine the repartition of these proteins in immune cells, their intracellular variation, at baseline and after cell activation and finally to understand the relation between their intracellular and extracellular expression. we used an in vitro model close to the immuno-inflammatory aggression that is septic shock. we stimulated in vitro for , and h whole blood from healthy volunteers using agonists found in the inflammatory storm that is septic shock (lps, fmlp, gmcsf, ifng). we also induced death cell, either using an apoptotic agonist, or by necrosis technics. we then analysed the intracellular variation of the calgranulins using flow cytometry technics. the extracellular quantification was made using elisa methods. all the statistic analysis were made using a mann-whitney test. we showed in this work for the first time that the intracellular repartition of the calgranulins is different depending on the type of cell: the complexe is the main form in the monocyte cytoplasma, whereas s a is the main intracellular form of the pmn. this repartition remains after cell activation. we also checked the absence of calgranulins in lymphocytes. after cell activation we showed that intracellular s a , s a and s a a increased, but at different levels depending on the cell and the agonist used. extracellular s a also raised after cell stimulation, but the concentration found were very low compare to those found in the plasma of septic shock patients. conclusions. together, these results suggest a different regulation depending on the form of the protein and of the cell and thus of proper distinct function of each monomer and of the complex. in the limits of our model the increased concentrations found in the plasma of patients with a septic shock can't be explained by immune cell activation. objectives. although there is no specific antidote for these potent toxins, drugs like penicillin g and silibinin have been used with conflicting evidence. we successfully managed two patients with mushroom poisoning by using silibinin and nac. methods. two members of a family, a mother years old, and her son years old were admitted to our icu h after the ingestion of wild mushrooms. they presented with abdominal cramps, vomiting, profuse diarrhea ([ /day), myalgias, confusion and agitation. the clinical examination showed severe dehydration, tachycardia, oliguria with grade i-ii hepatic encephalopathy. laboratory exams revealed elevation of liver enzymes sgpt: / u/l, sgot: / u/l. coagulation parameters were as following: prothrombin time . / . , factor v \ %/ %, factor vii \ / %. high ammonia levels were noted, reaching and ng/dl, respectively. metabolic acidosis was also present with mild renal dysfunction. the ultrasound performed in both patients showed hepatosplenomegaly. aggressive fluid and electrolyte replacement started upon admission. silibinin was given at a dose of mg/kg/day intravenously, in four divided doses, for three consecutive days, while nac was given as a continuous infusion at a dose of mg/kg for the first hour, mg/kg for the next h, and thereafter mg/kg/day for the following four days. hepatic encephalopathy, mild jaundice and renal dysfunction resolved within h, and liver function tests returned to normal within days. the patients recovered fully and were discharged to a medical ward. recent experimental and clinical studies have shown a strong protective and antioxidant effect against hepatic cell injury in amanita toxicity by the administration of nac and silibinin, either as monotherapy or as a combination therapy. although further clinical research is required to confirm their efficacy in reducing mortality and transplantation rate, nac has been used in our icu in hepatic dysfunction of different etiologies with promising results. we have recently shown that in patients with lactic acidosis due to metformin intoxication (serum drug level = ± lg/ml; therapeutic level is b lg/ml) systemic oxygen consumption (vo ) can be abnormally low despite a preserved global oxygen delivery (do ) ( ). the study, however, suffered from being retrospective. objectives. to prospectively clarify whether metformin primarily impairs vo . methods. eight sedated, paralyzed and mechanically ventilated pigs received a continuous i.v. infusion of metformin, at a rate of . g/h. the amount of metformin administered to each animal ranged from and g. the experiment always finished h after the initiation of drug infusion. use of sedative and neuromuscular blocking drugs, as well as ventilatory setting, were always kept constant. serum metformin concentration was measured at the end of the experiment, using high performance liquid chromatography (hplc). arterial ph, lactatemia, vo (indirect calorimetry) and do (computed from cardiac output measured by pulmonary artery thermodilution) were recorded hourly. data are presented as mean ± sd. statistical testing was performed using the one-way repeated measure anova and the linear regression analysis. metformin infusion produced toxic serum drug levels ( ± lg/ml; n = ). arterial ph drop from . ± . (prior to infusion) to . ± . (end of the experiment) (n = ; p \ . ) and lactatemia rose from ± to ± mmol/l (n = , p \ . ). vo progressively decreased (from ± to ± ml/min; n = , p \ . ) while do did not significantly change over time (from ± to ± ml/min; n = , p = . ). the decrease in vo was proportional to the dose of metformin administered (r . ; n = , p = . ) and to the serum drug level reached by the end of the experiment (r . ; n = , p = . ). conclusions. lactic acidosis develops during metformin intoxication in the presence of a diminished vo but in the absence of any clear evidence of inadequate do . this finding suggests that impaired oxygen utilization, rather than availability, may have a role in the pathogenesis of metformin-induced lactic acidosis. : min) . death was consequent to multiorgan failure, anoxic encephalopathy or capillary leak syndrome if ecls was performed under cardiac massage. four patients presented with documented brain death, allowing organ donation in cases. among these patients, the heart of one flecainide-poisoned patient was successfully transplanted, after normalization of ecg and myocardial function as well as toxicant elimination under ecls. prognostic factors in ecls-treated poisoned patients were as follows: qrs enlargement on admission (p = . ), saps ii score on admission (p = . ), ecls performance under massage (p = . ), arterial ph (p \ . ), lactate concentration ( . [ . - . ] versus . mmol/l [ . - . ], p = . ), as well as red cell (p = . ), fresh plasma (p = . ), and platelet (p = . ) transfusions within the first h. conclusions. to our knowledge, this is the larger series of ecls-treated poisoned patients ever reported. ecls appears to be an efficient salvage technique in case of refractory toxic cardiac failure or arrest, with a % survival rate. our series clearly demonstrate that toxic refractory cardiac failure remains the best indication with a % survival rate. objectives. aim of the study was to investigate the incidence of infections in patients treated with hypothermia while receiving sdd. in this retrospective case control study patients treated with prolonged hypothermia (cases) were identified and patients with severe brain injury were included (controls). propensity score matching was performed to correct for differences in baseline characteristics and clinical parameters. primary outcome was the incidence of infection. the secondary endpoints were the micro-organisms isolated from surveillance cultures and during infection. the demographic and clinical data indicated that the cases and controls were well matched. the length of stay in the icu and duration of mechanical ventilation were comparable between the groups. the overall risk of infection during icu stay was % in the hypothermia groups versus . % in the normothermia group (p = . ). pneumonia was diagnosed in . % of patients in both groups (p = . ). the incidence of meningitis, wound infection, bacteremia, and urinary tract infection was low and comparable between the groups. staphylococcus aureus was most frequently identified as the causative infectious microorganism in both the hypothermia ( . %) and normothermia ( . %) group (p = . ), followed by coagulase negative staphylococci ( . % in the hypothermia and . % in the normothermia patients, p = . ) gram-negative bacteria were isolated from the surveillance cultures in . % of patients treated with hypothermia and . % of patients in the control group (p = . ). colonization of the rectum with gram-negative bacteria was significantly more frequent in patients treated with hypothermia compared with normothermia ( . vs. . % respectively, p = . ). in contrast, colonization of the upper gastrointestinal tract and sputum was comparable between the groups with an incidence of . % in the hypothermia patients versus . % in the normothermia patients (p = . ). use of sdd mitigates the increased risk of infection in patients treated with hypothermia. based on the surveillance cultures, it seems that oropharyngeal decontamination is the most effective part of the sdd regimen in the prevention of pneumonia. introduction. prognostic scores specific for critical patients were developed in order to predict mortality based on physiologic and laboratorial variables. on the other hand, specific scores for burn patients are calculated taking into consideration inhalation injury, age and total burned surface area (tbsa), among others. however, scores utilized in general icu have not been evaluated in burn patients. objectives. therefore, the aim of the present work was to validate apache ii, saps as well as initial sofa in a population of patients with massive burn. these scores were compared to some specific burn patient scores, including absi (abbreviated burn severity index) and estimates of the probability of death. retrospective study employing data collected prospectively from may to february ( months) at an icu specialized in burn patients at a teaching hospital which is considered a reference centre in trauma care. all patients admitted during this period were included. one hundred and fifty-four consecutive patients were studied (male: %; female: %), with averaged age of . ± . years and a hospital stay of . ± . days. mortality rate of our sample was . %. incidence of inhalation injury was % and total burn surface area (tbsa) was the following: . % of patients had % or less; . % had - % of tbsa whereas . % showed % or more. area under curve of receiver operating characteristic (roc) of evaluated indexes is displayed on table . computerized head tomography is routinely performed as a diagnostic tool after the occurrence of neurologic deterioration in the icu adult patients. however, the ct findings in this setting are rarely reported. we hypothesized that the analysis of a series of cranial cts would help to understand the neurologic conditions of the critically ill patients and improve their management. objectives. to analyze, over a three-month period, the head ct scans performed in the adult icu in the albert einstein hospital in são paulo, brazil. methods. all cranial cts performed in the icu patients during the studied period were analyzed by two radiologists from the albert einstein hospital staff from may st to august st, , according to a pre-established protocol: . presence of acute cerebral ischemia; . presence of previous cerebral ischemia; . presence of acute cerebral hemorrhage; . presence of cerebral edema; . cerebral aneurisms; . cerebral tumors and . normal cerebral tomography. we studied ct scans from ( . %) males and ( . %) females, mean age . ± . years. the head ct findings were the following: ( ) presence of acute cerebral ischemia = ( . %); ( ) presence of previous cerebral ischemia = ( . %); ( ) presence of acute cerebral hemorrhage = ( . %); ( ) presence of cerebral edema = ( . %); ( ) cerebral aneurisms = ( . %); ( ) cerebral tumors = ( . %) and ( ) c years c , abc (assessment blood consumption) cp: c and ets (emergency transfusion score) cp: c , c years c . these scales handle the following combinations of variables for calculation: age, sex, type of admission, mechanism, blood pressure, focussed assessment for the sonography of trauma, hemoglobin, orthopedic or pelvic trauma, heart rate. mt was defined as the transfusion of units or more of packed red blood cells in the first h. we study the sensitivity (s), specificity (sp), positive and negative predictive value (ppv, npv), likelihood ratios positive and negative (lhr+ , lhr-) and area under the receiver operating characteristic curve (auroc) of different scales for the predictive power of tm validated in the literature. patients were available for analysis ( . % men, iss ± , blunt trauma . % objectives. we measured patient-reported outcome following surgical management with dc using a quality of life instrument. methods. survivors discharged between and months after severe tat were contacted after obtaining approval by our institutional irb. we excluded patients with neurotrauma. we applied self-response version euroqol questionnaire (eq- d) and visual analog scale (eq-vas: (worst health)- (best health). euroqol it is based on a descriptive system that defines health in terms of dimensions: mobility, self-care, usualactivities, pain/discomfort and anxiety/depression. each dimension has levels of response: no problems (level ), some problems (level ) severe problems (level ). results. thirty four patients were contacted. mean ± sd age was . ± . yrs, male were . % and penetrating trauma occurred in . %. mean ± sd in severity scores were: ati . ± . , iss . ± . and apache ii ± . the median time from discharge was months (iqr - months). the eq- d dimensions in which the largest proportion of patients reported severe problems were usual-activities (work, study) and pain/discomfort . % and . % respectively as shown in the conclusions. survivors of severe trauma and dc, reported acceptable quality of life with minimal limitations with social functioning. a prospective study should assess quality of life in these patients from hospital discharge and systematically over time. introduction. brain tumors surgery is one of the main causes of admittance to the nicu. it is important to know the risk factors associated to hospital mortality of patients admitted to nicu due to this reason. to identify perioperative factors associated to higher hospital mortality in a series of patients admitted to nicu immediately after a bt elective resection. methods. data of patients operated for bt elective resection and consecutively admitted to nicu at imss umae bajío were prospectively obtained. nicu bt database includes perioperative items. we divided the series in two groups: surviving and deceased patients. then, we analyzed the perioperative behavior differences between both groups. either student's t test or chi-square test was used, as it corresponded, for the analysis of differences observed between both groups. values of p lower than . were considered significant. results. the hospital mortality observed in this series of patients was . % ( / ). data of the nine variables showing significant differences between surviving and deceased patients groups are shown in table . even if hypoxic brain injury has been reported as the strongest factor affecting the poor outcome of near-drowning patients, little has been known about prognostic factors affecting the outcomes of those patients receiving mechanical ventilation. to define prognostic factors affecting the outcomes of patients mechanically ventilated after near-drowning. , white blood cell counts (or, . ; % ci, . - . ; p = . ), serum creatinine (or, . ; % ci, . - . ; p = . ), and serum lactic acid (or, . ; % ci, . - . , p = . ) were associated with favorable outcomes, respectively. however, only higher body temperature as a clinical parameter and the level of serum lactic acid as a laboratory parameter were significant predictors of favorable outcomes in multivariate analyses; the or were . ( % ci, . - . ; p = . ) and . ( % ci, . - . ; p = . ), respectively. conclusions. initial body temperature and the level of serum lactic acid were two most important clinical and laboratory prognostic factor in nearly drowned patients. the outcomes were not affected by the degree of initial hypoxemia. to determine the use of automated external defibrillators (aed) and manual defibrillators deployed in the various hospital wards (unmonitored areas) in a university hospital. a prospective study was performed according to utstein style of all cardiac arrests occurred in the hospital during the first months after the implantation of a new protocol of care for hospital cardiac arrest. because of this plan automated external defibrillators were located for hospital wards and common service areas (radiology areas, outpatients, …) where one would expect a lower incidence of cardiac arrests, according to the risk map elaborated previously. in areas of greatest risk manual defibrillators previously existed. all resuscitation attempts in these areas were analyzed, excluding the emergency department because of a separate protocol against the rest of the hospital. special attention was given to the use of aeds by wards staff before the arrival of resuscitation team. also a comprehensive volunteer training program was designed, but it began after the analyzed period was finished. results. during the first months we collected a total of pcr in hospital wards and public areas, with a median age of years and predominantly male ( patients). the most common origin was respiratory ( patients) followed by cardiac ( patients). the most frequent rhythm detected was non-shockable ( patients), only in was shockable and unknown in . before the resuscitation team arrival only two patients had been manually defibrillated and were never used the new aeds. conclusions. the aeds provided in the hospital were completely useless in the first months after placement, probably due to the lack of a comprehensive training plan associated to the population goal. methods. descriptive longitudinal study. patients were studied by encephalic death, as potential donors of organs, alerted to the network of regional transplant (cdtot), by units of intensive care, for months, in barranquilla's city. it was applied qualifying each of the variables in agreement to the vital opposing signs and biochemical tests brought in this moment. . . % of the subjects were male; the average of age was . years (±sd: . ). the values of blood sugar, sodium, osmolaridad, tonicidad, po , fc, pam, and glasgow, determined a score of , qualification that there had patient with encephalic death with the scale mbcm, as a test of certainty of the scale to diagnose encephalic death in total absence of reflections of stem. conclusions. there is recommended the application of mbcm's scale to every neurological patient by diagnosis of encephalic death in proof of certainty, in absence of others. by the high specificity of the already demonstrated scale there is recommended that scores lower than they should restate the qualification. a score of is an encephalic death in absence of reflections of stem. grant acknowledgment. clínica general del norte-cdtot introduction. prospective analysis of tracheostomies performed in patients admitted to a neurotrauma icu, the reasons for its implementation, and intraoperative complications in the first week. methods. all patients admitted to the icu of neurotrauma, which underwent a tracheostomy after admission. data were collected: affiliation, cause of admission, average stay, cause for realization of tracheostomy, tracheostomy time delay from its indication, place of performance of the procedure (icu or operating room), perioperative complications (event at transfer to operating room or during surgery: hypoxia, hypotension, arrhythmia, bleeding, premature extubation, false cannulation, cardiac arrest, pneumothorax or death), and postoperative complications in the first week (bleeding, difficulty in changing cannula, stomal infection, pneumothorax, death). introduction. the s- b protein is a brain-specific protein release from astroglial cells into the circulation after traumatic brain injury (tbi). researches indicate that the s- b serum level could be a useful indicator of tbi severity, however there is not evidence enough about the role of s- b in nonsevere head trauma. the hypothesis that s- b is a useful screening tool to detect brain injury in patients with a normal level of consciousness after a head trauma was tested. a total of patients with the diagnosis of mild tbi without decrease of consciousness (according to the gcs) with at least one neurological symptom or finding like amnesia, headache, dizziness, convulsion and vomits, were prospectively included. we recorded the clinical data on admission and a blood sample before h after tbi, for s- b inmunoluminescence analysis. a routine cranial computed tomography scan (ct) was obtained within h after the injury (categorized in normal or pathological). the diagnostic properties of s- b serum levels. lg/l, for prediction of intracranial lesions revealed by ct were tested with receiver operating characteristic (roc) analysis. seventy of the patients ( . %) were men, with a mean (sd) age of . ( . ) years (range, - years). a total of patients ( . %) had intracranial lesions. serum s- b levels were significantly higher in patients with intracranial lesions than in the remaining patients. the average value of the protein in patients without intracranial lesion was . lg/l with a ci % ( . - . lg/l), and in those with pathological findings in ct was . lg/l with a ci % ( . - . lg/l). significant differences were found between levels of s b protein and the presence of pathological findings in the ct (p = . ) (fig. ) . the roc curve analysis showed that s b protein is a useful tool to discriminate the presence of intracranial injury in ct (auc, . , % ci, . - . , p \ . ). s b analyses with a cut-off level of . lg/l showed a sensitivity % but a specificity . %. we evaluated different cut off values and in our series, the best cut off of the s b protein is at . lg/l with a sensitivity of % and specificity %. (fig. ) conclusion. determination of serum protein s- b is a useful biochemical indicator of brain damage in head trauma. our results show that an increase in the cut-off point of s- b to . lg/l increases its accuracy in the prediction of the existence of macroscopical lesions. key words. protein s- b, brain injury, minor head trauma, cranial computed tomography. critically ill patients with systemic inflammatory response syndrome frequently suffer muscle weakness due to critical illness myopathy (cim) and polyneuropathy (cip). several in vitro studies have shown that the cause of muscle weakness is a loss of membrane excitability accompanied by membrane depolarization [ ] . objectives. we investigated membrane polarization and excitability parameters in muscle and motor nerve in vivo within the first week after intensive care unit (icu) admission. methods. the study was approved by our local ethics committee. patients with sofa scores c on consecutive days underwent nerve conduction studies including direct muscle stimulation to categorize patients as icu-control, cim-(dmcmap \ mv) and/or cippatients (reduced snap amplitude) within the first days after icu admission. to assess excitability parameters we recorded stimulus-response behaviour, threshold electrotonus, current-threshold relationship and recovery cycle from abductor pollicis brevis muscle following stimulation of the median nerve [ ] . data are shown as median and %/ % percentile. conclusions. we describe for the first time that critically ill patients in general show muscle-and nerve membrane depolarization, whereas patients later suffering from muscle weakness due to cim or cim/cip feature additionally reduced membrane excitability. this suggests that membrane depolarization in critically ill patients is caused by energy failure leading to dysfunction of the na-k pump, the motor of membrane repolarisation-whereas reduced membrane excitability in cim or cim/cip needs an additional dysfunction of voltage gated sodium channels for example occurring in the presence of endotoxins [ ] . in intensive care patients with central nervous system (cns) disease, the systemic inflammatory response syndrome (sirs) criteria are often unreliable as a basis for identifying the inflammatory process. even with the presence of some infection they could be signs of the diencephalons-catabolic syndrome. diencephalons-catabolic syndrome like sirs constitutes of hyperthermia over °c, tachypnea of over per minute, tachycardia, and arterial hypertension. thus, sirs symptoms may occur after antibacterial treatment even if there is no infection or inflammation. we suggest a more precise method which could help to avoid the excessive antibacterial therapy and to control it in patients with cns disease-a procalcitonin test. objectives. reduce the use of wide specter antibiotics makes the control over antibacterial therapy in patients with cns diseases more precise; reduce the number of complications related to unnecessarily long antibacterial treatment. after obtaining the informed concern, in our investigation we included patients with different neurological disorders, who had recently transferred neurosurgical operations. all of them demonstrated sirs symptoms on different postoperative terms. when sirs symptoms occurred, we checked the level of procalcitonin in the patient's serum by a semi quantitative method on a disposable brahms pct-q system. the procalcitonin level was determined against a color scale. procalcitonin level over . ng/ml ( patients) considered a sign of infection and in such cases we prescribed antibacterial treatment , mg of selenase for - days. if the test result was negative ( patients) we repeated it in h and in cases with the same results, no antibacterial treatment was administered even if there were sirs symptoms. if pct-q test was negative patients were sedated (fentanyl . - . lg/kg/h and clonidine . - . lg/kg/h) to achieve autonomic stability and attenuate clinical manifestation of sirs. we had not observed any cases of sepsis in both groups of patients. by mince of pct, we had managed to reduce the quantity of wide specter antibiotics, used in neurosurgical patients for . %. conclusions. procalcitonin test in neurosurgical clinic let us determine the necessity of antibacterial treatment reduce the use of wide specter antibiotics, medical costs and prevent the forming of polyresistant infection. l. combe , r. appleton , c. gilhooly , j. kinsella university of glasgow, department of anaesthesia and critical care, glasgow, uk intensive care unit-acquired weakness (icuaw) is increasingly recognised as a common complication of critical illness with potentially prolonged debilitating sequelae. the estimated incidence is % in patients with sepsis, multi-organ failure or prolonged mechanical ventilation [ ] and suggested risk factors include: the systemic inflammatory response syndrome (sirs), sepsis, higher severity of illness, hyperglycaemia, renal replacement therapy and parenteral nutrition. objectives. the aims of this study were to determine the incidence, risk factors and outcomes for patients diagnosed with icuaw in glasgow royal infirmary's (gri) icu. the study was undertaken in two parts, firstly as a case-control study [matched for age (within years), sex and admission apache ii score (within points)] and secondly by comparing identified cases of icuaw to a -month cross-sectional sample ( / / - / / , patients) of gri's icu patients. data for both parts of the study was obtained from two electronic databases, wardwatcher and carevue. carevue was searched to identify patients with icuaw and wardwatcher was used to identify the controls. data collected included: patient and illness characteristics, severity of illness scoring, organ support and treatments provided, laboratory results and outcomes. minitab software was used for statistical analysis. conclusions. the incidence of icuaw was very low, we hypothesise this to be explained by the absence of systematic evaluation of patients for icuaw. the risk factors and outcomes for icuaw were consistent with some of the published literature. prospective study is now planned to systematically evaluate this condition. with increasing age, comorbidity, and socioeconomic deprivation being associated with higher risk pregnancies, there comes a potential higher risk of complications. neurological and neurosurgical complications, which can be particularly devastating during the peripartum period, include those due to medical conditions of pregnancy (hypertensive disease, sepsis, thromboembolic disease, hypoxic-ischaemic brain injury), iatrogenic complications secondary to anaesthetic or obstetric interventions, incidental illness or injury (pharmacological alterations, trauma, tumour), and deliberate self-harm and violence. objectives. to ascertain the frequency of neurocritical care admissions in the west of scotland, the nature of the admission diagnoses, the impact they have on our service (length of stay), and maternal and foetal outcome. methods. using the scottish intensive care society audit group wardwatcher patient database, female patients aged - years old who were admitted to the neurocritical care unit were identified (january -december ). we manually reviewed the electronic admission note for each of these women in order to gain diagnoses; a targeted case note analysis ensued. within the month study period there were a total of admissions to neurocritical care, of whom fulfilled the age and gender criteria; admissions ( . % of total) were for neurological complications in the peripartum period. the age range was to years (median years). three women ( %) were intrapartum ( - weeks gestation) at the time of their admission, and three were postpartum ( day- months). half of admissions were due to incidental illness or injury, a third to pregnancyrelated medical complications, and one case was iatrogenic in nature. length of stay in icu was to days (median . days). one patient sustained a residual facial nerve weakness and deafness. conclusions. this survey provided insight into the incidence and nature of pregnancyrelated pathology requiring acute referral to a regional neurosciences centre. as highlighted in other surveys, there may be many more peripartum patients with neurological complications who are cared for in general critical care units, and do not require admission to a tertiary referral centre [ ] . further work is underway to ascertain the true numbers of neurological complications of pregnancy countrywide. our approach represents a paradigm for the continuing audit of pregnancy-related critical care resource use in scotland. introduction. hypertonic saline has an osmotic effect on the brain because of its high tonicity and ability to effectively remain outside the blood-brain barrier. there may be a minimal benefit in restoring cerebral blood flow, which is thought to be mitigated through local effects of hypertonic saline on cerebral microvasculature. most comparisons with mannitol suggest almost equal efficacy in reducing icp but not compared their effects on eeg. objectives. we aimed to compare the effects of % mannitol, % or % hypertonic saline on hemodynamic parameters, intracranial pressure and electroencephalography in experimental head trauma. bilateral craniotomy were carried out in the parietal region and head trauma was applied for all rabbits. the rabbits were randomly divided into four groups. in group i rabbits were only observed. in group ii: % mannitol, in group iii: % hypertonic saline and in group iv: % hypertonic saline was administered intravenously to achieve similar osmolar load. electroencephalography, mean arterial pressure, heart rate, intracranial pressure were recorded before trauma and and min after trauma. results. increased intracranial pressure was significantly decreased by mannitol, and % hypertonic saline solutions at the end of study (p \ . ). but intracranial pressure values of mannitol and % hypertonic saline groups were lower than the other groups (p \ . ). the electroencephalography scores decreased after trauma in all groups (p \ . ). at end of the study, and % hypertonic saline groups had similar electroencephalography scores with pretrauma scores (p [ . ). the mean arterial pressure and heart rates increased after trauma in all groups (p \ . ). mean arterial pressure values were found lower only in mannitol group at end of the study (p \ . ). our study showed that when used in intracranial hypertension treatment, % hypertonic saline solution is as effective as mannitol, and preserves hemodynamic parameters, and normalizes traumatic electroencephalography abnormalities better than mannitol. objectives. to identify the causes of new onset seizures in patient admitted in medical icu. methods. all the patient admitted in icu and who had new onset seizures were evaluated. the patients were evaluated for metabolic profile. imaging (ct/mri) was done whenever needed. patients with preexisting seizure history were excluded from study. . ( males, females) patients, who had first seizure during hospitalization in icu were included. patients had generalised and one had focal seizures. patients had metabolic abnormalities. ( . %) had evidence of hepatic encephalopathy. ( . %) had only hepatic encephalopathy while rest had associated uremia, hyponatraemia, hypophosphatemia and hypomagnesemia. out of patients, who had renal failure, had evidence of uremia while rest had associated hyponatraemia or hypophosphatemia. only one patient had evidence of hypocalcemia. imaging was done in patients. ( %) had abnormal ct scan results. ( . %) had intracranial hemorrhage, ( . %) had infarct, ( . %) had brain metastasis, had evidence of hydrocephalus and one each had evidence of extradural hemorrhage and tuberculoma. csf analysis was done in ( . %) patients. ( . %) had evidence of tuberculosis and ( . %) had evidence of pyogenic infection. to study the role of various investigations and ct in evaluating these patients. all patients admitted with new onset seizures within h prior to presentation were included. all the patients were questioned and an attempt was made to assign an electroclinical syndrome to seizure. patients were evaluated for metabolic profile, neuroimaging. csf examination was done in those who had persistently altered mental status, infectious symptoms and fever. results. patients were admitted ( . % of total patients who came to emergency) with history of new onset seizures. . % patients were diagnosed to have acute symptomatic seizures and were placed in ilae category . and three patients were placed in ilae category of remote symptomatic seizures. the cause of seizures was established in ( . %) patients and remained unestablished in ( . %) patients. ( . %) patients were diagnosed to have neurocysticercosis. other important causes were acute infarct, uremia, hyponatremia, hypernatremia, viral encephalitis, post partum eclampsia, pyogenic and tubercular meningitis. alcohol withdrawal seizures were seen in . % patients. metabolic derangements were seen in ( . %) patients. computed tomography was done in patients and % had abnormal findings. mri was done in patients and had abnormalities. conclusions. neurocysticercosis was found to be most common cause of seizure activity in our part of country. though metabolic derangement can cause significant proportion of new onset seizure patients routine imaging of brain should be performed in patients with new onset seizures. work environment and organisational issues: - subjective and objective research into the working conditions and their effect on the health and safety of people working in icu, focusing mainly on the natural factors of temperature, humidity, ventilation, lighting and noise (part ) n. karachalios , e.c. katsilaki , d. sfyras general hospital of lamia, icu, lamia, greece the aim of the project is the subjective and objective investigation of the conditions of work and the relation repercussions on the health and safety of people working in the icu, focusing mainly on the natural factors that are likely to cause the sick building syndrome. for this purpose a protocol of research in two phases has been planned. the first included objective measurements, with the use of suitable equipment, of the natural factors of temperature, humidity, ventilation, lighting and noise. the second phase included the subjective estimation of the working people about their own health and conditions of their work, in the particular area of the hospital with the use of substantiated anonymous questionnaire. after the subjective and objective study and analysis of questionnaires and measurements of natural factors, we found that the medium temperature of the icu was °c. the mean relative humidity of the icu was % (highest . % and lowest . %). the mean ventilation rate of the icu was m /h (highest . and lowest \ . m /h). the mean sound pressure was . db (highest and lowest . db). the average lighting was . lux ( lux lowest and lux highest). the objective data seem to keep pace with the subjective opinions of the working people, as they were impressed in the questionnaires of subjective estimate. the objective data were compared with the subjective. the results of the research were also compared with data from the existing bibliography and current legislation, leading to a line of conclusions. ( ) insufficient and bad quality ventilation. ( ) the existing temperature of the environment contributes to the appearance of sick building syndrome. ( ) the working environment is noisy. ( ) the environment of work has problematic or insufficient lighting. ( ) the icu under study is a building area which can be characterized as ''sick'' if immediate action is not taken. background. up to % of critical care nurses test positive for (symptoms of) post traumatic stress disorder (ptsd) [ , , ] . it is assumed that these symptoms are caused by professional involvement in life-threatening events [ ] . in a sample of intensive care nurses, we investigated which work related incidents were perceived as most distressing. method. in interviews, nurses ( % female) were asked to memorize and tell about their most traumatic work related event. all interviews were recorded. after verbatim transcription, the 'most critical events' were extracted and categorized bij two independent psychologists. . none of the nurses reported major life-threatening events such as trauma-related injuries, massive bleeding or seeing patients die as their 'most critical incident'. conclusion. not the major life-threatening events but relatively 'normal work related events' under unusual circumstances are mentioned as most critical by nurses. in contrast to major life-threatening events, these 'normal events' are usually underestimated by colleagues, and thus potentially compromise peer-support. a care bundle refers to evidence based interventions and information grouped together to improve outcomes and consistency of provided care [ , ] . at the icus charge nurses and intensivists as shift leaders are responsible for daily management of unit activities. several immediately made decisions by shift leaders are made under time pressure and high information load with inadequate information. though we have evidence of structure and process based factors such as material and human resources, admission and discharge decisions or bed utilization, the support for information transfer and integration is poor in organizational decision-making concerning these factors. objectives. to identify immediate information needs of charge nurses and intensivists during the management of daily activities at the icu and evaluate how necessary this information is for their decision-making. from september to november , all charge nurses (n = ) and intensivists (n = ) of university affiliated icus providing comprehensive care in finland were surveyed with an on-line questionnaire using statements. the questionnaire was developed based on our previous observation study and statements of our survey regarded information needs related to the icu care activities. a rating scale from to (completely unnecessary-absolutely necessary) was used to assess the necessity of the information. for each statement, a response with mean or over was regarded as necessary information for immediate decisions. results. the response rate was . % (charge nurses . %, intensivists . %). the working experience varied from to years (mean . , sd . ). over % of respondents worked as a shift leader once a week or more often. statements of were valued as a necessary (mean [ or more) for immediate decision-making. absolutely necessary information (mean [ or more) for immediate decision-making were assessed related to the statements. these statements concerned isolations, mechanical ventilation, admissions and discharges, special treatments, patient's condition, and scheduled dates or times for surgery or other procedures. conclusions. both icu charge nurses and intensivists identified several information needs that are crucial for immediate decision-making during the whole icu care process. information needs of the shift leaders differed and they were strongly connected to the needs of one's professional requirements. an integrated overview and summarization of immediately needed information-a care bundle for organizational decision-making-at the icus is highly needed for icu shift leaders. the common interests of both professionals, charge nurses and intensivists, should be emphasized when new technology-based systems are developed. background. the nursing shortage is an international problem that is expected to worsen in the coming years. studies show that one of the main reasons nurses leave the profession is their dissatisfaction with their work environment. structural empowerment and nurse-physician collaboration are two elements of the nurses' work environment that are potentially related to one another according to kanter's theory ( ) . in addition, a nurse's clinical specialization has been found to influence perceptions related to these two concepts. to examine the level of perceived structural empowerment, the perceptions of nurse-physician collaboration and the relationship between these two variables, among intensive care unit (icu) nurses and general ward nurses in israel, and to compare the groups. a descriptive, correlational, comparative study design was used on a sample of icu nurses and nurses from internal medicine and general surgery wards in a large university hospital in israel (response rate %). a three section, self administered questionnaire was used to measure the study variables: the condition of work effectiveness scale-ii (cweq-ii), the collaboration with medical staff scale (cmss) and demographic-professional background. results: perceived structural empowerment was found to be moderate (m = . , sd = . , range = - ). nurses tended to agree that there was nurse-physician collaboration (m = . , sd = . , range = - , = strongly disagree, = strongly agree). a correlation was found between structural empowerment and the nurse-physician collaboration (r = . , p \ . ). a significant difference was found between icu nurses and general ward nurses on their perceptions of nurse-physician collaboration (t ( ) = - . , p \ . ; general wards: m = . , icu: m = . ). no significant differences were found between nurse specialization on perceived level of structural empowerment. conclusion. nurses in this study tended to agree that there was nurse-physician collaboration on their unit/ward. nurses who perceived themselves as having a higher level of structural empowerment, felt that there was a higher level of nurse-physician collaboration. general ward nurses had more positive perceptions about nurse-physician collaboration on their ward as compared to icu nurses. no difference was found between the two groups on the level of structural empowerment. recommendation. the findings of this study can be used as the basis for the design of interventions, aimed at enhancing structural empowerment and nurse-physician collaboration, in order to improve nurses' work environment, as one of strategy to decrease the nursing shortage. further study of additional hospitals in the country is also recommended. teams have expanded and in some hospitals h cover has been instituted. researchers are questioning the validity of outreach services and its impact on patient outcomes. as cco has been viewed as the panacea to all problems, data collection and analysis is fundamental in proving its financial and clinical benefits. objectives. this comparative study aims to evaluate retrospective data from month in and month in . data does not encapsulate patient outcomes; it will compare frequency of referrals and interventions. this data provides an indication to the extent cco has participated in the care of the acutely ill over a given time period. methods. data was collected from the d medicus database collating intervention data. analysis occurred using key interventions using excel software conclusions. whilst the validity of services has been questioned, the data itself indicates that more patients are referred and frequency of interventions has increased. various system changes occurred during this time period such as a change of mews trigger scores, the advent of h cco and courses such as alert and survive sepsis were introduced into the basic training of staff. it must be noted that the intention in the uk for cco was a service that empowered staff through education to undertake this care themselves; therefore the increase in interventions could indicate that the educational approach hasn't made progress. although the study compares interventions, an increase in the type of interventions was also noted such as ward based cco supervised cpap and establishing a picc line service. therefore this highlights the changing application of interventions. further analysis is required to look at the appropriate skills required for the delivery of safe care to the acutely ill in the ward environment. whilst ward staff are increasingly under resourced, both in skills and manpower, cco do provide the skills, knowledge and time to meet the shortfall in safe timely care. introduction. working as a critical care nurse involves situations where teamwork is essential and rapid, effective communication is of importance [ ] . the education to become a specialist icu nurse gives skills and knowledge to manage patients who are critically ill with rapidly changing conditions [ ] . experimental research is one way of contributing to the acquisition of such knowledge. to describe how icu nurses may contribute and perform in the experimental research process, an environment usually unfamiliar to them. we describe our experiences with regard to clinical contribution and our subjective evaluation of involvement in animal experimental research. method. three icu nurses in a swedish hospital were asked to participate in a research project investigating myocardial metabolism in porcine models of shock. the tasks were anaesthesia and pain management, assisting with catheter insertion and haemodynamic monitoring the pigs during the process results. although the situation was new, the nursing role and function in the team were at once similar and different to the daily work situation in the icu. one major skill learnt was the rigour of experimental measurements and sources of error, which is sometimes neglected in clinical care. being able to observe changes due to shock in a controlled setting, we improved our ability to critically 'think ahead' in anticipation of clinical deterioration [ ] . our first-hand experiences at the animal experimental laboratory allayed many anxieties and misconceptions with this type of research. conclusions. the critical care environment demands skills such as the ability to accurately define and change priorities rapidly, good communication and teamwork [ ] . we believe that the experimental research setting is one way of enhancing this ability. in these units patients condition may change rapidly and they may need close inspection as well as emergency response. early warning scoring (ews) system may make early recognition of and response to bad condition possible by observation based on systematic parameters. ews was developed as a simple scoring system to be used at ward level utilizing routine observations taken by nursing staff. ews is based on five physiological parameters; systolic blood pressure, pulse rate, respiratory rate, temperature and avpu score (alert; reacts to voice; reacts to pain; unresponsive). objectives. the aim of this study was to evaluate ews among patients admitted to pacu. methods. ews parameters were recorded four times from patients after their admission to pacu. the first record was taken during the first admission to pacu (ews ), the second (ews ) after min, the third after (ews ) and the fourth record after min. the correlation between variables like differences of four ews, patients age, the asa score, duration of operation were statistically examined. early treatment and recognition of sepsis is a stated aim of the surviving sepsis campaign [ ] but in busy clinical environments the delivery of antibiotics and fluids can often be delayed. we describe the implementation of an audit proforma, based on the survivesepsis.org [ ] resuscitation bundle, as a tool to deliver six aspects of management within h of recognition sepsis. . improve the early recognition and treatment of sepsis in acute medical patients. . provide a sustainable change in the management of septic patients . improve mortality and length of hospital stay methods. the proforma consist of six treatment management steps, based on the survivesepsis.org ''septic six'': oxygen, blood cultures, antibiotics, lactate, iv fluids, strict fluid management. it is triggered by patients satisfying two or more of the systemic inflammatory response syndrome criteria. all management steps should be implemented within h of the trigger time stated on the form. the forms are collected and analysed every month and the results are displayed for staff working on the medical admissions unit and accident and emergency. a total of forms have been collected, % diagnosed with severe sepsis. the progress on all six parameters is shown below. over the initial seven month period we have demonstrated a sustained improvement in the rapid delivery of all six of the management parameters. introduction. the early goal-directed resuscitation has been shown to improve survival in patients presenting with septic shock. a recent systematic review demonstrated the inability of central venous pressure (cvp) to predict the hemodynamic response to fluids infusion, and it should not be used to make clinical decisions regarding fluid management in critical patients. the clinical implication of this fact in septic shock is not well-known. objectives. the aim of this study is to determine if the resuscitation with fluids guided by cvp has clinical implications in patients with septic shock. post-hoc analysis of a patients' cohort with septic shock admitted in the medical intensive care unit since june to june . all of them were treated on basis of a bundle for severe sepsis management. chi-square analysis was used to compare categorical data. continuous data were compared using student's t test. we used multiple logistic regression model to assess the association between the independent variable and mortality, after adjustment for possible confusing factors (we considered variable to be confounding if the estimate of the coefficient changed by more than %). eighty-five patients were studied. % were male. their average age was ± and % had previous chronic diseases. severity scores: apache ii ± , sofa ± and % of patients had multiorganic dysfunction. infectious focus was respiratory in %. cvp mean was ± mmhg, scvo ± % and the mean amount of fluids provided was ± cc. % of patients needed mechanical ventilation. hospital-stay middle was days ( - ) and days in icu conclusions. in our patients' cohort with septic shock treated under the basis of the early goal-directed resuscitation, the volume of fluids infused was associated independently with mortality. a lower fluid administration in the resuscitation probably could be caused by the early reach of a high central venous pressure. blinding of study interventions is necessary to prevent bias in randomized controlled trials (rct). since normal saline and % albumin are packaged in bags and bottles, respectively and they have different color and texture, a blinding procedure is necessary to ensure the fluids appear identical for comparative rcts. objectives. to describe the blinding procedure and evaluate sterility and stability involved in the transfer and storage of study fluids in the precise pilot rct. a standard operating procedure for concealment, meeting pharmacy guidelines and good manufacturing practices was developed by the manufacturing pharmacist at the coordinating centre and used by all participating sites. fluids were transferred with aseptic technique into identical ml bottles under a sterile hood by the pharmacy or transfusion medicine technician then covered with an opaque wrapping. average time to transfer of study fluids from their original packaging was recorded to understand labor involved with creating each study fluid package. yellow intravenous tubing was manufactured to also conceal the fluid color. six blinded bottles of normal saline and % albumin from the participating centers were stored at room temperature for at least months. cultures of the fluids using blood culture media and/or endotoxin levels (measured by commercial assay) were obtained to document sterility of the study fluids. protein electrophoresis was used to assess albumin stability. results. transfer of the study fluids was the responsibility of the research pharmacist/ technician and blood bank at and sites, respectively. average time to transfer containers of normal saline and % albumin into bottles was ± and ± min, respectively. sterility (culture negative and/or endotoxin undetectable) of study fluids was confirmed from all bottles of normal saline and albumin that underwent testing. protein electrophoresis of albumin samples showed a single band suggesting no degradation of albumin during transfer and storage. conclusions. the standardized blinding procedure developed for transfer of study fluids in this pilot rct confirmed sterility and stability of our study fluids for months. these data are important when considering the length of allowable storage time for these study fluids. due to the resources and time involved with the transfer of these fluids for individual sites, this transfer method needs to be incorporated into budgeting and may not be feasible in the context of a large rct. grant acknowledgment. the precise pilot rct was funded by a grant from canadian blood services. covidien, singapore, singapore, yong loo lin school of medicine, national university of singapore, biostatistics unit, singapore, singapore introduction. the surviving sepsis campaign recommends a -h resuscitation bundle and a -h management bundle to improve outcomes in severe sepsis. compliance with and relevance of these recommendations to asian intensive care units (icus) are unknown. objectives. the primary objective of the present study was to assess the compliance of asian icus and hospitals to these bundles. the secondary objectives were to evaluate the impact of compliance on mortality, and the organisational characteristics of asian hospitals which are associated with higher compliance. methods. this was a prospective observational study of patients with severe sepsis who were admitted to the participating icus in july . we recorded the organisational characteristics of participating centres, the patients' baseline characteristics, and the achievement of targets within the resuscitation and management bundles. results. sixteen countries and icus participated, enrolling patients. hospital mortality was . %. achievement rates for the bundle targets were: lactate measurement, . %; blood cultures, . %; broad-spectrum antibiotics, . %; fluids ± vasopressors, . %; central venous pressure, . %; central or mixed venous oxygen saturation, . %; low-dose steroids, . %; drotrecogin alfa, . %; glucose control, . %; lung-protective ventilation, . %. compliance rates for the entire resuscitation and management bundles were . and . % respectively. on logistic regression analysis, achievement of the targets for blood cultures, antibiotics, and central venous pressure independently predicted decreased mortality. high-income countries, university hospitals, icus with an accredited fellowship programme, and surgical icus were more likely to be compliant to the resuscitation bundle. conclusions. compliance to the resuscitation and management bundles is generally poor across asia. given the resource limitations in asia, the most appropriate strategy to improve outcomes in severe sepsis may be to concentrate on ensuring early administration of antibiotics after blood cultures, and appropriate fluid therapy. cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study the work is supported by departmental sources. clinical features and prognosis of organizing pneumonia pre-senting as acute respiratory failure in icu reference(s). . webster nr. ventilation in the prone position prone position in acute respiratory distress syndrome effect of prone positioning on the survival of patients with acute respiratory failure acute effects of upright position on gas exchange in patients with acute respiratory distress syndrome this study was funded by arjo international ag, florenzstrasse d metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports longterm propofol infusion and cardiac failure in adult head-injured patients mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium intermittent haemodialysis versus crrt for arf in the intensive care unit dialysis dose in acute kidney injury: no time for therapeutic nihilism cirrhotics admitted to icu, and when added to the liver-specific scores of meld or ukeld, improves their respective predictive value intensive care, london, uk, royal free hospital epidural anesthesia, hypotension and changes in intravascular volume intraoperative fluid restriction improves outcome after major elective gastrointestinal surgery surrogate designation: can we trust our relatives? does chest physical therapy work? physiotherapy in intensive care: towards an evidence-based practice fisioterapia no paciente sob ventilação mecânica this research was supported by grants from the following brazilian funding agencies/programs: cnpq, capes, fapesc and unesc readmission to surgical intensive care increases severity-adjusted patient mortality physiological scoring systems and audit predicting death and readmission after intensive care discharge a case-control study of patients readmitted to the intensive care unit severity of illness and risk of readmission to intensive care: a meta-analysis a comparison of admission and worst -h acute physiology and chronic health evaluation ii scores in predicting hospital mortality: a retrospective cohort study learning from the past to inform the future-a survey of consultant nurses in emergency care assessing emergency nursing competence post-traumatic stress among swedish ambulance personel levels of mental health problems among uk emergency ambulance workers partial and full ptsd in brazilian ambulance workers: prevalence and impact on health and on quality of life ambulance personnel and critical incidents impact of accident and emergency work on mental health and emotional well being artemis health institute, director, critical care, pulmonology and sleep medicine, gurgaon, india, artemis health institute, nursing, gurgaon, india reference(s) the australian incident monitoring study in intensive care: aims-icu. the development and evaluation of an incident reporting system in intensive care adverse events in critical ill patients ministry of health and social policy communication: a key factor in the patient safety? anemia of the critically ill: acute anemia of chronic disease impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient high dose recombinant human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome: the journal of trauma: injury, infection and critical ca to the staff of the critical care department, faculty of medicine injury severity and quality of life: whose perspective is important? quality of life and persisting symptoms in intensive care unit survivors: implications for care after discharge variations in health-related quality of life in critical patients funded in part by fogarty international center nih grant no. d tw - and clinical research institute-fundacion valle del lili glasgow coma score, use of mechanical ventilation and vasoactive agents, and the occurrence of severe sepsis (according to bone's criteria- ). the causes of admission were divided as: ischemic stroke, hemorrhagic stroke, subarachnoid hemorrhage, status epilepticus, traumatic brain injury, elective neurosurgeries, and miscellanea. the foci of infection, microbiological data and bacteremia were analyzed from septic patients. numeric data were expressed as median and interquartiles, while categorical data were calculated as percentage. univariate and multivariate (logistic regression) analysis was carried out to point factors associated with hospital mortality. results. we included patients, with median age years (iq range - ) and % were male %) patients, while it occurred during icu stay on ( %) patients. hospital mortality was associated with age, the admission cause (higher for hemorrhagic stroke, traumatic brain injury and status epilepticus), apache ii score, glasgow coma score and severe sepsis on the univariate analysis cnpq perioperative factors associated to higher mortality in patients admitted to the neurological intensive care unit (nicu) immediately after brain tumor (bt) resection saldívar umae (high-specialty medical unit no ) el bajío, imss and nicu, hraeb (high-specialty regional hospital of el bajío) anaesthesiology and intensiv care medizin anaesthesiology and intensive care unit charité universitätsmedizin-berlin, department for anesthesiology and intensive care medicine after approval of the local ethics committee, the pdr icg was measured within h post injury (day ) using the non-invasive limon system (pulsion medical systems of pdr icg to supranormal values higher sofa scores were indirectly associated with lower pdr icg values, particularly for sofa scores[ . when patients were grouped by icu length of stay (\ , c days, corresponding to the mean icu los of the german trauma registry), logistic regression analysis identified pdr icg consumables were provided by pulsion medical systems influence of apoe polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury genetic variation of the apoe promoter and outcome after head injury effects of apolipoprotein e genotype on outcome after ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage the association between apoe « , age and outcome after head injury: a prospective cohort study decreased cerebrospinal fluid apolipoprotein e after subarachnoid hemorrhage correlation with injury severity and clinical outcome « association of ventilation rates and co concentrations with health and other responses in commercial and industrial buildings « sensitivity to noise, personality hardiness, and noise-induced stress in critical care nurses recommended lighting level for offices » the chartered institution of « sick building syndrome, sensation of dryness and thermal comfort in relation to room temperature in an office building: need for individual control of temperature silent misery: most severe critical incidents post traumatic stress disorder in the emergency room: exploration of a cognitive model trauma exposure and post-traumatic stress disorder in intensive care unit personnel increased prevalence of post-traumatic stress disorder symptoms in critical care nurses drivers of quality in health services: different worldviews of clinicians and policy managers revealed systems thinking, system dynamics the fifth discipline: the art and practice of the learning organisation the development of system dynamics as a methodology for system description and qualitative analysis finnish funding agency for technology and innovation nursing activities score tradução para o português e validação de um instrumento de medida de carga de trabalho de enfermagem em unidads de terapia intensiva: nursing activities score (nas) nursing activities score in the intensive care unit: analysis of the related factors the self-perceived health between medical-surgical and crit-ical care nurses in hungary deutsch , i. boncz , a. sebestyen , a. olah university of pecs faculty of health sciences a longitudinal study design was used to explore the self perceived health of inhospital nurses in acute care settings (surgery, casualty, internal medicine, intensive, coronary care, emergency room) in two hungarian factors predicting team climate, and its relationship with quality of care in general practice nurse working conditions, organizational climate, and intent to leave in icus: an instrumental variable approach critical care nurses' work environments: a baseline status report quality of practice in an intensive care unit (icu): a mini-ethnographic case study vasps/intv ). medicinska fakulteten, lunds universitet critical thinking and clinical decision making in critical care nursing assessing and developing critical-thinking skills in the intensive care unit gulhane military medical academy, haydarpasa training hospital, istanbul, turkey, gulhane military medical academy technology as a catalyst to transforming nursing care devices and desire: gender, technology and american nursing surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock division of pulmonary and critical care medicine, seoul, republic of korea, peking union medical college hospital, department of critical care medicine mai hospital, intensive care department, hanoi, viet nam, king saud bin abdulaziz university for health sciences, king abdulaziz medical city, intensive care department dr soetomo general hospital, department of intensive care republic of china, ripas hospital, intensive care unit surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock the surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis great differences in compli-ance with surviving sepsis campaign bundles surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock delayed diagnosis is associated with increased morbidity, mortality and cost in the icu. as the mortality rate of severe sepsis remains unacceptably high, a group of international expert developed guidelines in , termed the surviving sepsis campaign (ssc). the ssc group has introduced the ''sepsis care bundles surviving sepsis campaign guidelines for severe sepsis and septic shock implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality improving outcomes for severe sepsis and septic shock: tools for early identification of at-risk patients and treatment protocol implementation observational, prospective follow-up. patients who were admitted into the intensive care unit in university hospital complex a coruña (chuac) during the months of hospital mortality was surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock early goal-directed therapy in the treatment of severe sepsis and septic shock associated with decreased mortality translating research to clinical practice: a -year experience with implementing early goal-directed therapy for septic shock in the emergency department improvement in process of care and outcome after a multicenter severe sepsis educational program in spain duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock delta co (pvco -paco ) as a prognostic factor in septic shock septic shock using the new device inspectra : relation to macro-and microhemodynamic and outcome c. luengo , , f. vallée , c. damoisel , m. resche-rigon among the techniques assessing microperfusion, near infrared spectroscopy (nirs) gained interest. more than baseline sto values, the reperfusion slope after a vascular occlusion test (vot) nirs parameters, especially the reperfusion slope scvo or svo ); metabolic (ph, base excess and lactate) parameters were collected. microperfusion data consisted in: nirs (baseline sto , occlusion and reperfusion slopes (%/s), automated software); skin laser doppler microflow (baseline flow (tpu), peak flow (tpu) and slope during reperfusion (tpu/s), measured during and after a min vot. survivors (s) and non-survivors ] differed between s and ns at day . macro-hemodynamic and metabolic data did not differ between s and ns plan quadriennal ea svo does not predict fluid responsiveness in critically ill septic patients supported by msm research grant: replacement of and support to some vital organs years) were studied. apache ii and sofa score at study entry were (range: - ) and (range: - ) respectively. the septic syndrome was due to sepsis (n = ), severe sepsis (n = ) or septic shock (n = ). sites of infection included the lung reference(s). . ungerstedt u: microdialysis: principles and applications for studies in animals and man the pathophysiology and treatment of sepsis management of sepsis surviving sepsis campaign guidelines for management of severe sepsis and septic shock relation between muscle na + k + atpase activity and raised lactate concentrations in septic shock: a prospective study long-term continuous glucose monitoring with microdialysis in ambulatory insulin-dependent diabetic patients whether it is worth to correct acidemia by infusion of alkaline solutions is a matter of discussion. there are a number of evidences against the use of alkalinization therapy with respect to the benefits of reversing ph and the side effects of sodium bicarbonate infusion [ ]. nonetheless, as recently shown by means of an on line survey, % of critical care physicians administer base to patients with lactic acidosis mmol/l), animals were randomized to min of: a) sustained lactic acid infusion, a + b) sustained infusion + sodium bicarbonate, o) transient infusion, b) transient infusion + sodium bicarbonate. in the transient infusion (group o and b), at randomization lactic acid was replaced with normal saline. acid-base status and lactate levels were measured over time. in a number of animals phosphofructokinase (pfk) enzyme's activity was also measured. results. following lactic acid infusion blood lactate rose unnecessary use of alkali perturb acid-base status and lactate metabolism potentially overcoming metabolic adaptive strategies. reference(s). . boyd jh, walley kr. is there a role for sodium bicarbonatein treting lactic acidosis from shock? use of base in the treatment of acute severe organic acidosis by nephrologists and critical care physicians: results of an online survey strong ions gap (sig) quantifies unmeasured blood anions and it is calculated by the difference between strong cations and strong anions (all of them, dissociated in blood plasma) retrospective, observational study of all patients with septic shock as defined by the american-european consensus, admitted to the icu from arterial blood gases, albumin, lactate and electrolytes were obtained at admittance and h later; apache and sofa score, central venous saturation and lactate comparison of acid base models for prediction of hospital mortality following trauma forty-five sepsis patients [median age, (iqr, - ) years; admission saps ii, ( - ) pts; severest multiple organ dysfunction syndrome score interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial lambert university of leicester, division of anaesthesia, leicester, uk blood samples were taken: at induction of anaesthesia, at and - h post-cpb. neutrophils were isolated, mrna extracted, dna cleaned and reverse transcribed supported by a grant from the association of anaesthetists of great britain and ireland, and the british journal of anaesthesia/royal college of anaesthetists secretoneurin (sn), a neuropeptide, is specifically expressed in endocrine elevated nucleosome levels in systemic inflammation and sepsis extracellular histones are major mediators of death in sepsis rd esicm asymmetric and symmetric dimethylarginines (adma, sdma) are protein-breakdown markers; both compete with arginine for cellular transport and are excreted in urine. moreover adma, sdma, their ratio (marker of adma catabolism), arginine, interleukin- (il- ), tumor-necrosis-factor-a (tnf-a), c-reactive-protein(crp) on day , , , , and at discharge in consecutive severely-septic patients were measured sdma were higher than normal, adma/sdma ratio was halved, arginine was low. adma was related to total sofa and arginine, inversely related to il- and crp; sdma was related to saps ii, sofa, blood urea, creatinine, arginine. adma/sdma ratio was inversely in non-survivors, creatinine, il- , tnf-a, crp and adma were stable, sdma increased, adma/sdma ratio remained low figure: time course of adma and sdma blood levels (mean ± standard error) during icu stay and the last icu day protein-hmgb- levels as predictors of outcome in patients with sepsis and septic shock hmgb as a predictor of organ dysfunction and outcome in patients with severe sepsis early low dcs counts may be correlated to disease severity and could predict fatal outcome. however, little is known about dc number in other shock than septic. objectives. to evaluate and compare the circulating dcs number in patients with severe sepsis, septic or cardiogenic shock. methods. in a prospective multicentric study ( icu), consecutive immunocompetent patients with severe sepsis (ss), septic shock, cardiogenic shock were included. peripheral blood dc counts, measured by flow cytometry, were evaluated and compared between the three populations at admission and h later. correlation to disease severity evaluated by clinical scores and day mortality was studied. results. patients were included (age ± years, male, sofa d . ± . , saps ii ± ): septic shock, severe sepsis and cardiogenic shock. mortality at d was respectively , and %. patients presented a sepsis associated to cardiogenic shock. at baseline and at day , a dramatic diminution in the numbers of total dcs either myeloid (mdcs) or plasmacytoid (pdcs), was observed in sepsis (severe sepsis or septic shock) compared to cardiogenic shock patients. no difference was seen between severe sepsis and septic shock patients (fig. ). we did not observe any correlation between the number of total dcs at admission or at day and severity of illness scores dc reduced number is a valuable marker of severe sepsis in shock and is not affected by hemodynamic changes. it could not be used as a prognostic marker in severe septic patients. preliminary results from a prospective study assessing the relationship between standard laboratory coagulation and global tests of clot-formation using thromboelastography in patients with fulminant hepatic failure v the routine use of international normalized ratio (inr) to establish the coagulation status in patients with fulminant hepatic failure (fhf) may be misleading. anecdotally, fhf patients, despite a significantly deranged inr, may display a normal or even hypercoagulable state, as recently shown, albeit in an extracorporeal setting, with frequently clotted circuits, despite raised pt we prospectively studied coagulation, demographic, survival and outcome measures of fhf patients (defined by de-novo liver failure, coagulopathy-inr [ . , and encephalopathy) admitted to the royal free hospital liver and/or intensive care unit(s) (icu), a tertiary referral centre in liver diseases and transplantation we present the standard clotting tests and teg results from (of a required ) patients currently enrolled, demonstrating variable degrees of encephalopathy and coagulopathy effect of norepinephrine on cardiac output and preload in septic shock patients apparent heterogeneity in splanchnic vascular response to norepinephrine during sepsis aggressive use of high-dose norepinephrine in the treatment of septic shock norepinephrine requirement is not an independent variable to predict outcome in severe septic shock patients aim. the aim of this study was to measure the level of ptsd among hungarian ambulance workers, and explore factors which can influence it.sample and methods. hungarian ambulance workers were involved to this crosssectional study ( ambulance drivers, ambulance nurses, and ambulance team leaders: medical doctors and ambulance officers). self filling questionnaire were used for data collection, including briere's trauma symptom checklist, and socio-demographic questions. chi square test, independent t test and variance analysis were used for comparison of variables.results. the average ptsd-points of ambulance workers was . there was significant association between level of ptsd and gender: women's average , men's average ptsd-points (p = . ). there were no correlations between level of ptsd and type of settlement, location of ambulance station and level of education. those who would need psychological support (p = . ), and those who had psychologically traumatic experiences in the last years have significantly higher ptsd-points (p = . ).conclusions. hungarian ambulance workers are exposed with many effects which can lead ptsd. professional psychological support is needed in order to cope with ptsd successfully.the results were presented and discussed in our weekly meeting on patient safety and healthcare for all icu personnel. by the end of this year all the recommendations will be implemented in our icu.conclusions. we improved the safety and quality of in hospital transportation of icu patients by performing a prospective risk analysis. bow-tie is a good instrument to identify health care risks. to determine the incidence of phrenic neuropathy associated with the catheterization of internal jugular and subclavian veins, without ultrasound support, in patients admitted to an icu. a prospective study was performed by following patients admitted in the icu between october and may . a normal neurography of both right and left phrenic nerves at the moment of their admission was the main inclusion criteria. after this baseline study, a new neurography was repeated weekly (chen and resman method, sinergy medelec), during their stay and at the moment of being discharge from icu. simultaneously, all vascular subclavian and internal jugular vein catheterization were registered. a final neurography and a fluoroscopy study were performed after being discharged from hospital. results. patients were included and two hundred and ten neurographies of both right and left phrenic nerves were performed. patients did not receive any vascular punctures in the cervical region during the follow up period, acting as control group. patients underwent a total of vascular catheterization, in subclavian vein ( . %) and in internal jugular vein ( . %). a phrenic neuropathy was diagnosed in patients. this represented an incidence of % ( / ) of phrenic neuropathy per patient and % ( / ) related to subclavian and internal jugular vein catheterization. in relation to patients without phrenic nerve injury who underwent subclavian and internal jugular vein catheterization, patients affected of phrenic neuropathy had longer mechanical ventilation time ( ± days vs. ± , p = . ) and longer average stay time in icu ( . ± days vs. ± , p = . ), although these differences have not statistical significance. we did not find significantly differences related to age ( ± vs. ± , p = . ) and apache ii index ( ± . vs. . ± . , p = . ) between both groups (wilcoxon two-sample test). we performed a control neurography of case patients after being discharged from hospital. we checked the cmap phrenic nerve reappearance after weeks and months of being diagnosed its neuropathy, respectively. conclusions. we found an incidence of phrenic neuropathy of % per patient and % related to subclavian and internal jugular vein catheterization, during the follow-up period. the time of reappearance of phrenic cmaps after being detected its neuropathy points to a neuroapraxia or partial axonotmesis as pathogenic type of injury.discussion. phrenic neuropathy has to be considered in cases of difficult weaning of unclear etiology. the catheterization of subclavian and internal jugular veins should be recommended employing ultrasound support. p. merino , m.c. martin-delgado , j. alvarez , i. gutiérrez-cía , Á . alonso-ovies , syrec hospital can misses, icu, ibiza, spain, isde, Á rea de salud, madrid, spain, hospital de fuenlabrada, icu, madrid, spain, hospital clínico universitario, icu, zaragoza, spain introduction. syrec project aims to improve icu patient safety. the project includes an epidemiological study. we present the main results.objectives. to estimate the near miss (nm) and adverse events (ae) rate in spanish intensive care units (icus). we study the incidence and nature. finally, we classify and analyze its severity.methods. multicenter prospective observational cohort study. inclusion criteria: patients admitted to the participant icus during the -h observation period. during this period, nm and ae detected and reported inside and outside icu were included. only outside icus were considered when its were the reason for admission. we evaluate the kind of incident, severity and preventability. data collection studied under the distribution of frequencies.results. , patients were included. , incidents were reported in patients, were nm and ae. risk: the median risk of nm was % versus ae %. . incidents per patient admitted. incidence rate: the incident rate median was . per patients per hour icu stay, the nm of . per patients per hour icu stay and that of ae, . per patients time of stay in icu. the % of the incidents reported have been nm and % ae. this incidents causing temporary damage in the . % of occasions and in the . % permanent damage, compromised the patient's life or contributed to death. classification of incidents (table ) . conclusions. our study shows a high individual risk. our icus services present a highrisk environment. therefore we have to go into the developement of epidemiological studies depth, in order to create further strategies supporting patient safety. restore cardiovascular performance in severe lactic acidotic rats a. kimmoun , n. sennoun , n. ducrocq , b. levy , inserm u , groupe choc, vandoeuvre-lès-nancy, france, chu nancy brabois, intensive care unit, vandoeuvre-lès-nancy, france introduction. lactic acidosis during shock is responsible for myocardial failure, vascular hyporesponsiveness and a decrease in sensitivity to vasopressor agents. sodium bicarbonate is a proposed treatment to correct acidosis, although with deleterious cardiovascular effects. indeed, hypocalcemia and hypercapnia, both powerful myocardial depressants, are the main side effects of the administration of this therapy [ ] . objectives. already studied in experimental models of isolated lactic acidosis, the cardiovascular effects of sodium bicarbonate administration have never been explored after correction for hypocalcemia and hypercapnia. methods. we therefore compared, in a rat model of severe lactic acidosis (ph \ . , hyperlactatemia[ mmol/l) induced by a state of controlled hemorrhagic shock, the cardiovascular effects of: ( ) standard resuscitation plus administration of sodium bicarbonate with correction for calcemia and paco (''adapt'' group, n = ); ( ) standard resuscitation plus administration of sodium bicarbonate without correction for paco and calcium (''nonadpat'' group, n = );( ) standard resuscitation; (''stand'' group, n = ); ( ) standard resuscitation plus calcium administration (''calc'' group, n = ). evaluation at steady and shock state, min and min was focused in vivo on arterial gas and myocardial contractility (emax) by conductance catheter. ex vivo vasoreactivity was tested on mesenteric arteries ( lm) by myography. sodium intakes were equivalent between groups. results. our model displayed a profound acidosis from . to . ± . (p = . ) and hyperlactatemia from . ± . to . ± . mmol/l (p \ . ). emax decreased from . ± . to . ± . mmhg/ll p = . . in the adapt group, at min, ph was normalized at . ± . (p = . ). furthermore, emax was enhanced at ± % (p \ . ) (stand: ± %, nonadapt: ± %, calc: ± %). the cumulative dose of infused norepinephrine was significantly lower in the adapt group ± lg/kg compared to other groups (stand: ± lg/kg, nonadapt: ± lg/kg, calc: ± lg/kg, p = . ). ex vivo mesenteric vasoreactivity in the adapt group was normalized (graph ).mesenteric vasoreactivity to phenylephrine conclusions. in severe lactic acidosis, infusion of sodium bicarbonate after correction of its side effects improves myocardial function and vasoreactivity. [ ] . the prevalence and significance of -hydroxyvitamin d deficiency in the intensive care unit have not been fully determined. a recent study of an unselected group of itu patients [ ] has suggested low itu admission -hydroxyvitamin d levels are common. objectives/hypotheses to be tested. royal free hospital intensive care unit patients exhibit low circulating levels of -hydroxyvitamin d. circulating levels of -hydroxyvitamin d decrease further during the course of hospital admission. admission circulating levels of -hydroxyvitamin d affect itu morbidity and mortality methods. all itu admissions were assessed within h of presentation and patients who were deemed to have the potential to require admission for at least week were included. demographic and clinical data were obtained in a prospective manner. results were recorded from samples obtained at admission, days and days. standard itu nutrition protocols were used. no interventions were performed. results. clinical and outcome data were obtained for patients. no significant differences between apache , saps or apache scores for survivor and non-survivor groups at either itu or hospital discharge were noted. further patients await complete data analysis. % ( of for whom results were available) achieved an adequate ([ nmol/l) circulating hydroxyvitamin d level. patients ( . %) demonstrated levels within the insufficient range ( - nmol/l). patients ( . %) did not have any detectable -hydroxyvitamin d. the remaining patients ( . %) were either in the deficient ( . %, - nmol/l) or severely deficient ( . %, - nmol/l) ranges. admission -hydroxyvitamin d levels in survivors and non-survivors were compared at itu and hospital discharge. no significant differences between the four groups (p [ . , anova) were observed, indicating that in this data set, admission -hydroxyvitamin d levels do not appear to alter or determine clinical course. mean -hydroxyvitamin d levels were compared at admission, day and at day . no significant differences between the three groups (p [ . , anova) were identified. no significant differences between the mean -hydroxyvitamin d levels of the survivors and non-survivors at day or day were apparent (small numbers). admission [ , ] and patients undergoing surgical procedures [ ] . patients with neurological illness can receive significant quantities of ns, chosen primarily for its iso-osmolar properties. objectives. ns is commonly used as maintenance and resuscitation fluid by the anaesthetist, and as intravascular flushes by the radiologist during prolonged interventional neuroradiological (inr) procedures. this pilot feasibility study aimed to ascertain the effect of ns infusion on acid-base measurements in patients undergoing inr procedures under propofol-remifentanil anaesthesia. methods. we collated routine electrolyte, albumin and acid-base data of patients who underwent coil/glue embolisations of intracranial aneurysms and vascular malformations, both before and after the procedure. base excess (be) was partitioned into the effects of sodium chloride difference (na-cl), albumin, lactate and unmeasured anions (uma), using the stewart-fencl-story approach [ ] . all values are reported as medians (ranges objectives. to investigate the erythropoietic response to hight dose of a weekly schedule of recombinant human erythropoietin (rhuepo) in critically ill anaemic septic patients. a total of patients admitted to the intensive care unite (icu) were enrolled in this study, patients were randomized to receive either rhuepo or not, patient did to form the rhuepo group, did not to form the control group.results. the epo treated group of patients showed significant increase in reticulocyte count compared with baseline p \ . , as well as with the control group p \ . . the epo treated group exhibited also a significant increases in hb concentration compared with baseline p \ . as well as the control group . . all patients in the control group received rbc blood transfusion %, while only . % of the epo group did. the epo treated group showed significant decreases in their apache ii score during the study period compared with baseline p \ . as well as with the control group p \ . . the epo treated group showed no significant difference in their sofa score compared with baseline p \ . , however the control group exhibited continuous and significant increase in their sofa score throughout the study period compared with their baseline p \ . , there was no significant difference in the final outcome recovery, mortality or morbidity p . , p \ . respectively.conclusions. the administration of rhuepo to critically ill anaemic septic patients is effective in raising their reticulocytic counts, hb concentrations and in reducing the total number of units of rbcs they require. in addition there was a trend toward better in hospital clinical course, increased recovery and decreased mortality in the rhuepo group.conclusions. anaemia is common following critical illness but does not appear to affect the physical aspects of recovery during medium term rehabilitation. this may be due to an overwhelming degree of symptom burden from other complications of critical illness impairing physical function to such a degree that the effects of anaemia are negligible in the medium term. although decreases in number and function has mainly been described in skeletal muscle, also other organs seem to be affected and it has been hypothesized that mitochondrial dysfunction might be involved in the development of organ failure. to study the effect of plasma of patients with septic shock on mitochondrial function in vitro to potentially later on identify a central factor affecting mitochondria in all tissues during sepsis and leading to multiple organ failure.methods. after sacrificing - week old sprague-dawley rats, mitochondria from soleus muscle were isolated through homogenization and a series of centrifugations. mitochondrial function was assessed by measuring of oxygen consumption, using an oxygraph containing a clarke-electrode, after addition of adp. before these measurements, mitochondria were incubated with plasma from septic patients or healthy volunteers, respectively, for min. in our second series, the mitochondria were incubated with different concentrations of il- , tnf-a or buffer. respiration rates were measured in the presence of adp (state ; a measure for the oxidative capacity to produce atp) and without the presence of adp (state ; a measure for the amount of uncoupling). respiratory control ratio (rcr; a measure for the respiratory efficiency of the mitochondria) was calculated by dividing state by state activity. all measurements were related to citrate synthase activity to compensate for the amount of mitochondria. statistical differences between the groups were analyzed using a student's t test.results. adp dependent (state ) respiration was % higher and rcr % higher in the mitochondria incubated with plasma from the septic patients compared to those incubated with plasma from healthy volunteers (table) . there were no significant differences between the groups incubated with preservation buffer or the different cytokines (table) . introduction. microvascular fluid loss from the intravascular to the interstitial space generates tissue edema and is one of the major challenges in emergency and intensive care medicine. isolation of interstitial fluid (if) from skin makes it possible to study the microcirculation and proteins in this environment both during normal as well as pathophysiological conditions such as acute inflammation.objectives. by studying bio-markers from proteomic analysis by mass spectrometry in an inflammation model, we wanted to find proteomes that could be important in explaining inflammation. we have applied a recently described centrifugation method in a porcine model and compared it with implanted wicks. in nine anesthesized piglets we compared the methods and evaluated the if, by overhydrating the pigs with ml of acetated ringer's solution for h, and thereafter continuously supplemented for h according to fluid losses. if was isolated from implanted dry wicks, wet wicks and by centrifugation of excised skin. the methods were evaluated by the ability to reflect overhydration and to show the expected composition of plasma proteins in if by use of hplc. the if was also processed further with mass spectrometry to find possible tissue degradation or inflammation due to overhydration. statistics: by spss v . and graphpad instat (version . ). significance level: p = . . colloid osmotic pressure in if was significantly lowered after overhydration for all the tree methods. wet wicks p = . , dry wicks p = . , skin samples p = . . hplc of if collected with centrifugation after overhydration, identified peaks representing molecules smaller than albumin. mass spectrometry of the same if identified several proteins associated with inflammation: alpha- -antichymotrypsin and lumican, the latter a protein identified as a modulator of inflammation. we have introduced a new centrifugation method for isolation of if from the skin of pigs. by further analysis of if isolated by centrifugation we were able to distinguish proteins found only in the if of the pigs overhydrated with ringer's acetate. these proteins could be associated with an inflammatory condition in the skin caused by massive overhydration, again causing tissue degradation. identification and validation of proteomic biomarkers can be a useful tool in future treatment of inflammation in general, and in sepsis in special. objectives. to define the pattern of change in metabolites by mrs in experimental sepsis. male sd rats (weight - g) underwent cecal ligation and puncture or sham procedure (n = per group), and h after surgery were euthanized. pulmonary tissue was extracted for magic angle mrs (hr-mas) and processing by the r metabonomic package. a supervised statistical analysis of main components (mc) was performed on the processed spectra.results. the mc analysis discriminated both group (septic and nonseptic) indicating a different metabolite profile. in addition, the analysis of mc loading revealed displacement positions in the discrimination between groups with a variation in the signal intensity of %.conclusions. metabolomic analysis of pulmonary tissue by mrs is a potentially useful technique for the detection of biomarkers in sepsis.grant acknowledgment. introduction. cd + cd + neutrophils are a key subset of phagocytes associated with severe bacterial sepsis [ ] . their characteristics, and potential neuro-immunomodulation, have not been explored in humans neutrophils exposed to septic plasma from icu patients. to assess the effect of adrenergic/cholinergic neurotransmitter molecules on human neutrophil adhesion and activation markers following exposure to human septic plasma. with irb approval, neutrophils were isolated from healthy volunteers (ficoll density gradient separation) and incubated for h with either plasma from healthy volunteers or septic patients plus pathophysiological concentrations of epinephrine (e), norepinephrine (ne) or acetylcholine (ach) and nicotine (nic) to assess potential parasympathetic-related neuro-immunomodulation. flow cytometry (dako cyan) measured expression on neutrophils of cd , cd , cd antibody markers and viability. median values are shown; analyzed by anova.results. neutrophils were unaffected by ne, e, ach or nic after incubation with plasma from healthy volunteers. after incubation with septic plasma, marked neutrophil activation occurred (p = . ). however, nic reduced cd + cd + activation (* fig. a ) by % (median ( - %; th- th centiles); p = . ). nic also attenuated cd expression, suggesting reduced neutrophil adhesion (* fig. b) . neutrophil viability was similar across drug and plasma treatments. conclusions. these preliminary data suggest that nicotine attenuates both the activation and adhesion of human neutrophils exposed to human septic plasma, but does not affect viability. objectives. the aim of this study was to evaluate the potential impact of lag between sepsis initiation and start of treatment on mitochondrial respiration. methods. animals [ . ± . kg] were randomized (n = /group) to a control group (group i) and three groups resuscitated at (group ii), (group iii), and (group iv) hours, respectively, after fecal peritonitis induction. fecal peritonitis was induced with instillation of . g/kg of autologous feces via intra-peritoneal drain. resuscitation was performed according to the ssc and esicm sepsis guidelines for h. respiration of permeabilized skeletal muscle fibers and their isolated mitochondria was assessed at baseline and after , , , and h, when applicable, or before death occurred, if earlier. at the end of the experiment, also isolated brain, hepatic and myocardial mitochondrial respiration was measured using high resolution respirometry (oxygraph- k, oroboros instruments, innsbruck, austria). results. mortality ( %, each) and organ dysfunction was highest in groups iii and iv. in these two groups, different pattern of changes of skeletal muscle mitochondrial complex i-dependent respiratory control ratio (rcr) were observed (table ) . no significant differences between groups were observed for complex i-and ii-dependent rcr values of hepatic, myocardial and brain mitochondrial respiration (fig. ). there were no significant differences between the groups for any of the complexes in permeabilized skeletal muscle fibers mitochondrial respiration (data not shown). conclusions. despite the high mortality observed in groups resuscitated at later time points after induction of sepsis, end organ mitochondrial function assessed using physiological substrates was preserved. despite significant changes in skeletal muscle mitochondrial respiration efficiency in the two groups with the highest mortality, our findings do not support the view that mitochondrial dysfunction plays a major role in the pathogenesis of multiorgan dysfunction in experimental sepsis. grant acknowledgment. swiss national fund, nr: - ; stiftung für die forschung in anästhesiologie und intensivmedizin. adipose tissue is an endocrine organ which produces signalling proteins involved in inflammation and glucose homeostasis [ ] . one of these proteins, adiponectin, promotes glucose utilisation and fatty acid oxidation and thus improves insulin sensitivity via its two receptors, adipor and adipor [ ] . adiponectin expression has been shown to be reduced in type ii diabetes, obesity and endotoxaemia [ , ] . adiponectin also exhibits antiinflammatory properties [ ] . in this study, we have examined whether adiponectin and its receptor gene expression changes in murine adipocytes stimulated by lps. methods. t --l adipocytes were grown in culture media (dmem with % fetal calf serum) until confluent. pre adipocytes were differentiated with the addition of mg/ml insulin, mm dexamethasone and mm ibmx. media was changed every h. cells were treated on day with ng/ml, or mcg/ml lps (escherichia coli, sigma-aldrich). cells were harvested at and h. mrna levels were determined by rt pcr in a . ll reaction volume consisting of . ng of reverse transcribed cdna mixed with optimal concentrations of primers and probe and qpcr tm core kit (eurogentec, uk) in -well plates on a mx p detector. results. cell response to lps was confirmed using il as a reference gene. expression of adiponectin mrna was significantly reduced in cells treated with lg/ml lps harvested at h ( . fold p = . ). there were no changes in cells treated with lower concentrations of lps. there were no changes at h. r gene expression was significantly reduced following treatment with ng/ml lps at h ( . fold p = . ), but treatment with higher concentrations did not change expression. there were no changes at h. r expression levels were significantly reduced at h in the and the mcg/ml groups ( . fold p = . and fold p = . ) respectively. there were no changes at h. discussion. our results add to the evidence that changes occur in the adiponectin system during inflammation. in this model, we observed rapid reduction (at h) in adiponectin at high dose lps, r at low dose lps and r at medium and high doses. there were no changes in expression levels at h. this suggests that a rapid change in the adiponectin system may occur in response to lps but this change is not maintained at h. in a previous study, our group has shown reduced adiponectin gene expression in adipose tissue depots in lps induced endotoxaemia [ ] . it is interesting that different concentrations of lps induce different changes within the adiponectin system. further studies are needed to elucidate whether reductions in both adiponectin and its receptor may contribute to the inflammatory changes and hyperglycaemia commonly observed during sepsis including all co poisoned patients treated with hyperbaric oxygen. following parameters were seized: age, sex, date of admission, sofa, the source of the intoxication, the gravity co score, the initial clinical examination (realized by first aid), biology, the rate of hbco, the murray score and the rate of complication. results. patients were included in the study. the sex ratio was %, the mean age was ± years and the global mortality was , %. among the patients % were poisoned by smoke (s group), % by pure co (c group) and % by exhaust fumes. more than % of the exhaust fumes victims were suicide origin. this characteristic is associated with neurological impairment induce by ingested drugs. then, their neurological status is impossible to link to the co poisoning. we have therefore decided to exclude this group. the sofa score was higher in the s group compared with the c group ( . - . ; p \ . ). a co score equal to was present in versus % respectively in s versus c group (p \ . ). in the under group of patients having a co score at , % ( / ) of co poisoned patients versus . % ( / ) of smoke poisoned patients were ventilated (p \ . ). these patients were intubated either during transport or in the intensive care and none of them received hydroxycobalamine during the first aid (before intubation). the laboratory data showed in the s group a higher lactates level ( . vs. . mmol/l; p = . ) and lower initial pao /f i o ratio ( vs. ; p = . ). nine percent of the s group present a murray score at versus % for c group (p \ . ). pneumonia, shock and death were significantly more frequent in the s group (respectively . vs. . %, p \ . ; . vs. . %, p \ . ; and . vs. . %, p \ . )conclusions. as expected the smoke poisoned group has a higher mortality than pure co group (mortality % vs. overall mortality . %). at equivalent co gravity score, mortality and complications are always more frequent in the smoke poisoned group. the smoke poisoned group has a high risk of degradation. those patients require specific monitoring and support and probably early administration of hydroxycobalamine. hypothesis. at administration and maintaining higher plasma levels of at can reduce the need for inotropes in burn shock patients. we performed a retrospective cohort study of burn shock patients admitted to a single tertiary care center over years period. patients were eligible for inclusion if they were received fluid resuscitation with ringer's solution and colloid according to clinical guidelines. data were abstracted including demographic, burn injury characteristics, resuscitation fluid volume, the type of colloid and the average of plasma at levels within h after burn injury. administration of fresh frozen plasma and/or recombinant human at was defined as at administration. the decisions of at administration and inotropic support (dopamine or dobutamine) were made by the attending intensivists. primary outcome measure was the need for inotropes within h after burn injury. cox regression model was used to estimate the risk reduction by at administration and average of at levels. [ ] . argon, another member of the noble gas family has been reported previously to have a neuroprotective property [ ] . the aim of this study was to investigate whether it attenuates neuronal injury in a rat model of neonatal asphyxia. methods. seven-day-old postnatal sd rats underwent right common carotid artery ligation and then recover with their dim for h. thereafter, they were exposed to % o balanced with nitrogen for min. after h, they were treated with % argon or % nitrogen (positive control group) for min. the cohort pups without intervention served as naïve control. they were perfused days later and their brains were sectioned and stained with . % cresyl violet. microphotographs were taken from ca area of the hippocampus near - . bregma relative to adult brain at magnification. healthy cells were counted in a blind manner and their mean value was used for data analysis. results. the thickness of healthy layers in the right ca area of the positive control group was remarkably reduced compared with other groups (fig. ). quantitative analysis revealed that argon treatment significantly increased healthy cell numbers in the right ca area of hippocampus from . ± . in the positive controls to . ± . (p \ . ) (fig. ). grant acknowledgment. this study was supported by a grant from action medical research, uk. objectives. our objective was to study the mechanisms of death following high-dose citalopram administration in rats. experimental study in sprague dawley rats with intraperitoneal (ip) citalopram administration; determination of the median lethal dose (mld)using the dixon and bruce upand-down method; clinical descriptive study of citalopram-induced features and measurement of alterations in respiratory pattern (arterial blood gases and plethysmography) and biological parameters including blood lactate (scout Ò , ekf diagnostic), plasma and platelet serotonin concentrations (high-liquid performance chromatography-fluorometry); determination of the preventive activity on seizures and death of diazepam, cyproheptadine, and propranolol pretreatments with the determination of their minimal effective dose; comparisons using anova for repeated measurements followed by bonferroni post-test.results. citalopram ip-mld was determined as mg/kg in rats. seizures were significantly increased in rats receiving and % of citalopram mld versus controls (p \ . and p \ . , respectively), while death rate was only significantly increased in rats treated with % of citalopram mld (p \ . ). significant decrease in body temperature was observed after min in rats treated with doses[ % mld in comparison to controls (p \ . ). occurrence of serotonin behavioural syndrome was comparable in all groups. citalopram administration did not result in significant hypoxemia, hypercapnia, and lactate elevation, thus not supporting the hypothesis of the occurence of any significant deleterious cardiovascular effect in citalopraminduced toxicity. however, a significant moderate increase in the inspiratory time (p \ . ) accompanied with an expiratory braking was observed. a significant decrease in platelet serotonin and increase in plasma serotonin concentrations were measured (p \ . ). pre-treatment with diazepam ( . mg/kg) and cyproheptadine ( . mg/kg) of rats receiving a lethal citalopram dose prevented seizures and death, while propranolol was ineffective.conclusions. citalopram respiratory toxicity remains mild, while deaths result from seizures probably related to serotonin toxicity. our observations may be helpful to better understand and manage human citalopram poisonings. objectives. to define the population pharmacokinetics (pk) of phenytoin in the critically ill, in addition to risk factors for sub-therapeutic dosing.methods. free and total ptn concentrations were measured in serum by means of high performance liquid chromatography following microfiltration, two to three times in the first h after a loading dose. population pk modelling, including intra and interindividual variability, were determined using nonmem (r) . in the netherlands the use of diazepam is advised as first line treatment although evidence is not established and mainly provided through case-reports [ ] . to compare the effect of diazepam on mortality in (hydroxy) chloroquine intoxication to standard therapy. we performed an extensive medline search ( -april ) with a manual reference search of identified papers. (hydroxy) chloroquine intoxication studies and case reports in english, dutch or french were evaluated. patients older than years with severe intoxications, based on measured concentrations or life-threatening symptoms, were included. pooled relative risk (rr) for mortality with corresponding % confidence interval (ci) were calculated by means of a fisher exact test. our results were compared with two retrospective and one prospective study.results. there were case reports identified from which case reports met our inclusion criteria. thirteen patients received diazepam of whom two died, compared to twelve patients who did not get diazepam of whom one died. statistical analysis demonstrated that treatment with diazepam was not associated with a lower mortality rate (rr: . ci . - . ; p = . ).although pooling of case reports is debatable, these results were comparable to the retrospective and prospective studies that didn't show any benefit from diazepam in chloroquine intoxication [ , , ] . the positive effect of diazepam may have been underestimated, due to the fact that it has been given only as rescue therapy.conclusions. based on our analysis there is a lack of evidence concerning any antidotal effect of diazepam. good supportive treatment is pivotal. if the clinical manifestations of (hydroxy) chloroquine intoxications require sedation or treatment of seizures, diazepam is a good choice based on its pharmacological profile. a prospective study which compares diazepam to sedativa with similar pharmacokinetic and dynamic profile is required to prove that diazepam has any antidotal effect. introduction. brain is one of the first organs affected in sepsis and evaluation of brain function is difficult since patients are under sedation. it has been shown that mitochondrial dysfunction may play a significant role in the pathogenesis of septic encephalopathy. here we investigated inflammatory and metabolic parameters in a model of polymicrobial sepsis in mouse. methods. sepsis was induced by intraperitoneal injection of feces. animal received imipenem h after the procedure. control animals received intraperitoneal saline and imipenem after h. blood cytokines and serum lactate were measured. the animals were sacrificed by cervical dislocation. brain slices of mcm were used to measure oxygen consumption and glucose uptake.results. interleukin , mip a and interleukin b significantly raised in the first h after sepsis induction (p = . ; p = . ; p = . respectively). in h only mip a was significant higher (p = . ). lactate was elevated and h after sepsis induction (p \ . and p \ . respectively). oxygen consumption increased after h of sepsis and drops under control values h after the induction of sepsis. glucose uptake, measured by the nbdg fluorescence, was higher after h (p = . ) and h after sepsis induction.conclusion. in a murine model of abdominal sepsis, inflammatory markers, lactate production, and brain glucose uptake increased and were parallel to alterations in the mitochondrial oxygen metabolism. introduction. the royal bournemouth hospital has one of the highest out-of-hospital cardiac arrest admission rates in the uk. in , following ilcor/aha guidelines [ ] , a cooling protocol was developed for patients with return of spontaneous circulation after advanced life support for ventricular fibrillation or pulseless ventricular tachycardia. in preparation for potential new ilcor/aha guidelines in , the prospective database of outcomes for these patients was analysed.objectives. to evaluate the outcomes of therapeutic hypothermia for patients with return of spontaneous circulation following cardiac arrest. outcome data from our prospective registry of cooled patients are summarised.results. sixty-three patients were cooled in years (median age years; mode ; range - years). % survived to itu discharge and % to hospital discharge. % of these were discharged home ( % to a rehabilitation hospital before home and one patient to a long term care facility). ninety-five percent of survivors were alive at months and % alive at year with seven status results still pending. median itu length of stay was . days (range - ). six patients required temporary percutaneous tracheostomies for airway protection and weaning from ventilation. median duration from itu to hospital discharge was days (range - ).conclusions. this series is large by comparison to other uk centres. survival to hospital discharge, at months and year were better than other published results. although neurological outcomes were not formally assessed, we believe that the capacity to discharge home is a desirable patient outcome and represents the beneficial neurological effect of our cooling protocol. selection bias will have undoubtedly affected our results. however the age of our patients was higher than in published trials and in other reports is considered an adverse outcome predictor. our data would not support restricting induced hypothermia on the basis of age alone. we consider the itu and hospital lengths of stay required to discharge these patients to be long. these data were not reported in original trials. discharges may obviously be delayed for non-clinical reasons. this aside, neurological recovery progresses for months after cardiac arrest and discharge home may still prove possible if time is allowed. however, post-itu resource implications should be considered when introducing a cooling protocol. introduction. acute ischaemic stroke (ais) is the third largest cause of mortality and the leading cause of chronic disability in the industrialized world. in some parts of europe and the united states - % of patients with ais may be admitted to a neurological intensive care unit (icu) for supportive therapy with - % receiving mechanical ventilation [ , ] . there are currently no agreed uk criteria for the admission of ais patients to critical care.objectives. to review the incidence and outcome of ais in our tertiary icu over the last five years. november and november . ais was classified as thrombo-occlusive or embolic. subarachnoid haemorrhage and primary intracerebral haemorrhage were excluded. demographic and outcome data were recorded and compared against a mean value of all icu admissions.results. ais comprised . % of icu admissions during the study period. demographic data is presented in table as mean ± standard deviation or median (interquartile range) as appropriate. in % ( / ) of hospital ais admissions were admitted to icu. patients had surgical procedures including decompressive craniectomies. % of survivors had a discharge gcs of / . mortality for unselected medical admissions over the study period was %. there are differences of significance in the mortality according to the age, classified by age groups with an age cut off of years (\ years . vs. c years %, p \ . ). apart from the gcs, the rest of the variables analyzed in the ich score are not of significance; supra and infratentorial, presence of intraventricular blood neither on the divided volume over or under cc although, in the latter, a p \ . can be observed and if we only analyze the supraventricular, it comes out as significant. other analyzed data are the time of the surgery, which is not significant, the need for mechanical ventilation, which is ( . vs. . %, p \ . ), and the days of ventilation with a mortality clearly higher on those patients with\ days of ventilation ( %) and on those of shorter stay (lesser then days %).conclusions. let be remarked that the samples have been taken from patients admitted in the intensive care unit, losing a possible sample of less serious patients, and with a higher level of consciousness, what might explain why supra or infratentorial location and the volume don't come out as forecasting factors, since its likely that there are many small infratentorial outside the intensive care unit. we highlight also that the high mortality in the first few days can be caused by those patients who are admitted as donors, developing an encephalic death in the first days, conditioning also the data regarding the mortality on fewer days with ventilation. the finish up, we have to point out the fact that the presence of previous hypertension during the treatment might be a bad forecasting factor that should be deeper studied. to determine whether a delay exists between the time of diagnosis of intracranial haemorrhage and the time of reversal of anticoagulation, in patients presenting within our region. following approval by all audit and haematology departments a month retrospective analysis was performed. we reviewed consecutive patients who received reversal of anticoagulation with pcc and vitamin k having presenting with intracranial haemorrhage whilst on warfarin. time of diagnosis was obtained from the time of scan and time of pcc issue was obtained from the blood bank database. case note analysis was performed to obtain further information.results. patients were identified, in the neurosurgical centre and in peripheral hospitals. the median time from scan to issue of pcc was min. patients were reversed within min and patients waited longer than min to have pcc issued. no adverse thromboembolic events were encountered.conclusions. avoidable delay exists between ich diagnosis and pcc issue. pcc could be stored in the emergency department and a stat dose administered immediately after diagnosis facilitating rapid correction of inr. repeat audit will be required to assess safety and efficacy. objectives. the aim of this study was to compare the functional ability and muscle strength between these two groups of patients. twenty-nine patients were evaluated (m: , f: ) (age: ± years).the diagnosis of critical illness polyneuromyopathy was based on muscle strength measurement according to the medical research council (mrc) of muscle strength methodology. nine patients were diagnosed with critical illness polyneuromyopathy during their icu stay (mrc \ / ).the patients were evaluated with mrc and hand-grip dynamometry (hgd) every days until their discharge from the hospital. the fim scale (functional independence measure) was used to evaluate the functional ability ( - ).the first evaluation was done at the discharge from the hospital and the second one ± months afterwards.results. the patients who developed critical illness polyneuromyopathy had statistically significantly lower mrc ( ± vs. ± , p \ . ) and hgd at icu discharge (left ± kg vs. ± , and right ± kg vs. ± , p \ . ) compared to those who did not. the muscle strength as assessed with the mrc days after icu discharge had statistically significantly lower ( ± vs. ± , p \ . ), just as the second hgd evaluation (left ± kg vs. ± and right ± vs. ± kg, p \ . ).compared to those who did not develop critical illness polyneuromyopathy, the patients who did, had statistically lower fim values during their discharge from the hospital ( ± vs. ± , p \ . )and months afterwards ( ± vs ± , p \ . ).conclusions. the patients who developed critical illness polyneuromyopathy had significantly inferior muscle strength at their discharge from the icu. these patients also had lower functional ability. this functional ability remained defected even months after their discharge from the hospital. these initial findings are suggestive that the appearance of critical illness polyneuromyopathy affects the patients mobility after their discharge either from the icu or from the hospital and persists for several months after icu discharge. further studies are needed to evaluate the effect of this impairment on the quality of life of these patients and also to evaluate therapeutic tools for critical illness polyneuromyopathy. introduction. this poster presents a qualitative system dynamics (sd) analysis of the factors which influence the care of acutely unwell ward patients in new zealand. this systems thinking approach is commonly used in organisational research and offers a way to make sense of complex relationships between variables. this approach has previously been used in health care to demonstrate differences in mental models between policy makers and clinicians (cavana et al., ) . since the factors which influence the care of acutely unwell ward patients are complex and multi faceted the qualitative sd method becomes an ideal analytic approach (e.g. see wolstenholme and coyle, ; senge, ; vennix, ; or maani and cavana, ) .objectives. the aim of this study was to examine the factors which influence the care of acutely unwell ward patients from an organisational perspective. key objectives were to determine the enablers and barriers to care from a nursing, medical and managerial (at ward and executive level) perspective.methods. using a multiple case study approach in four wards in two new zealand hospitals, focus groups and one to one interviews were conducted with key stakeholders identified as nurses, doctors and managers. initial coding of the data generated themes. these themes were then clustered to provide variables which were mapped to generate separate causal loop diagrams (clds) for each of the stakeholder groups to provide the basis for analysis. the clds were compared for characteristics and world views. preliminary results demonstrate a difference between clinical and managerial staff in characteristics and world view regarding the factors which affect the care of acutely unwell ward patients.conclusions. the qualitative sd approach has offered a novel and helpful way to make some sense of the complexity associated with caring for acutely unwell ward patients. organizational responses that may improve care delivery to these patients should be based on frank and open discussions between staff at all levels to ensure a shared mental model as the basis for change. objectives. the aim of the study is to explain the nursing in the technologicallyadvanced intensive care units. in this phenomenologically-designed study, a face-to-face in-depth interview was performed with nurses, who were experienced for - years in the intensive care unit of cardiovascular surgery clinics. during the interviews, a semi-structured form was used. data were analysed using colaizzi's method of data analysis. the study was approved by the ethics committee of the institution.results. according to the nurses, nursing in technologically-advanced environment has three stages. these stages constituted three themes of the study: technology shock (first stage), understanding the technology-supported care (second stage), competency in technological environment (last stage). in the first stage, the nurses focus on themselves and technology; perceive the environment as frightening and complex. in the second stage, nurses gain control on technology, feel themselves safe and recognize their responsibility. in the last stage, the nurses experience anxiety related to their accountability. this anxiety may be motivating but also may be wearisome.conclusions. the nurses passes through three stages in a technologically-advanced environment. helping nurses to pass through these three stages appropriately will increase the contribution of technology to the patient care, more utilization of technology by nurses and more job satisfaction. unexpectedly, the compliance rate with the recommendations was significantly better over night. although the number of nurses is constant in the h, the number of doctors is lower and less differentiated in the night shift. in an attempt to find an explanation for these findings we looked at the patient flow and time span until the first medical observation in the different time periods and we found that over night admissions (between : a.m. and : a.m.) corresponded only to % of all admissions and were seen sooner, which might explain our findings. a. objectives. the purpose of the study was to assess whether the completion of the sepsis resuscitation bundle within the first h after icu admission, but beyond the specific time limit of the various bundle interventions, is related to an improvement in survival in patients with severe sepsis/septic shock. this was a single-center prospective observational study of patients admitted to the medical-surgical icu of an urban tertiary care teaching hospital with severe sepsis/septic shock. patients were recruited from june to november . we assessed the compliance with the different tasks included in the -h resuscitation bundle. furthermore, we ascertained within the first h after icu admission the compliance with those tasks not carried out within their specific time limits; we have called this variable ''bundle improvement at the icu''. results were stratified by the number of tasks of the bundle completed before admission at the icu, and the lag time between the beginning of severe sepsis and admission to the icu. these late completed tasks at the icu were related to hospital mortality by a cox regression model. objectives. the aims of this study were to assess the compliance rate with h bundle as defined in the surviving the sepsis campaign guidelines in patients diagnosed with sepsis regardless of severity and whether compliance affects the rate of mortality and/or hospital stay. we conducted a prospective observational study. we randomly recruited adult patients from acute admissions unit and intensive care in an acute district general hospital in england who met the diagnostic criteria for sepsis. for each patient, compliance with sepsis care bundle was obtained from medical notes. the following components of the h sepsis bundle were assessed: obtaining blood cultures, initiating antibiotic therapy, measuring serum lactate and in the event of septic shock administration of fluid therapy. conclusions. long and unacceptable delays in admission to iccu were identified despite evidence of significant organ dysfunction in many of these patients. with all bundle elements being met for only patient it is apparent that evidence based endpoints aimed at reducing mortality from severe sepsis are not being met despite all the bundle elements being practically deliverable. poor compliance with taking blood cultures prior to antibiotic administration and lack of scvo measurement are areas requiring particular attention. further work is recommended to identify potential contributing factors to non-compliance. introduction. international guidelines recommend that cardiac output measurement is required in addition to arterial pressure monitoring in patients with persistent shock after initial therapy [ ] . nevertheless, these recommendations are not supported by any comparison of arterial pressure and cardiac output for monitoring the effects of the most current treatments like fluid therapy. objectives. to evaluate in which extent monitoring the haemodynamic effects of a standardized fluid challenge with the sole arterial pressure could help for detecting the fluidinduced changes in cardiac index (ci). in critically ill patients with acute circulatory failure deemed at receiving a -ml saline infusion over min, we measured the systolic (sap), diastolic (dap), mean (map) and pulse (pp) arterial pressure and transpulmonary thermodilution ci before and after volume expansion.results. volume expansion significantly increased ci, sap, dap, map and pp by ± %, ± %, ± %, ± % and ± %, respectively. the fluid-induced changes in pp, sap and map were significantly correlated with the fluid-induced changes in ci (r = . , . and . , respectively). the changes (in %) in pp were significantly related to the changes (in %) in stroke volume for all quartiles but with different coefficients of correlation: r = . for the st quartile ( - years), r = . for the nd quartile conclusions. pp and sap were the best arterial pressure values for detecting the fluidinduced changes in ci. using the sole pp for assessing fluid responsiveness led to a non negligible proportion of false negative cases. this supports the recommendation that when a precise monitoring of fluid resuscitation is required, like in refractory shock, a direct assessment of cardiac output is required. objectives. aim of our study is to show that it is possible to reduce high catecholamines in previous improper volume resuscitated patients by forced volume resuscitation combined with active dose reduction and generate the hypothesis of an avoidable catecholamine induced circulation injury. introduction. the sialic acid content of the red blood cell (rbc) membrane decreases early in sepsis [ ] , and this alters the rbc shape and metabolism [ ] . an increased ratio of the rbc proteins band /alpha spectrin was observed in a mouse model of septic shock, suggesting a possible alteration of the rbc membrane integral/peripheral proteins ratio [ ] . as there are interspecies differences in membrane composition, these observations need confirmation in humans. we studied rbcs from patients with (n = ) and without (n = ) sepsis at icu admission and on day in the septic patients. exclusion criteria were recent rbc transfusion, hematologic diseases, cirrhosis and diabetes mellitus. procedures included screening for rbc membrane protein alterations by cryohemolysis test and separation of the rbc membrane and skeletal proteins by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate [ ] . comparison between groups was made by the student's t test or the mann-whitney test. a p value . was considered as statistically significant.results. the hemogram, including reticulocyte count was similar in septic and non-septic patients at icu admission. no significant difference was observed for cryohemolysis test results and the amount of the rbc proteins (table ) . objectives. our purpose was to compare a new method (patrol fr - ) with the reference method (randox tm ) during cbp. patients scheduled for coronary artery bypass (cb) and aortic valve replacement (avr) under cbp were enrolled after written informed consent in this protocol approved by local ethics committee. anesthesia protocol was standardized with systematic use of tranexamic acid. three blood samples were harvested: t = induction; t = min. after cross aorta clamping; t = h after induction. the patrol method was performed after serum exposition to a photosensibilizer agent then to a laser irradiation leading to the formation of free radicals. oxidation by those free radicals of a fluorometric sensor allowed an indirect measure of tas. this measurement in arbitrary unit (au) corresponded to area under curve compared to a control value from a pool serum. a value higher than indicated a lower capacity for the given serum to neutralize free radicals whereas a lower value indicated a higher capacity. the same sample allowed tas determination (lmol/l) with randox tm method. results were expressed as absolute numbers, mean ± sd. tas were compared with anova test; p \ . was significant.results. the seven patients ( male, female; ± years old) enrolled underwent cardiac surgery ( cb and avr) without any problem. there was no variation in tas determination with the randox tm method: t : . ± . ; t : . ± . ; t : . ± . lmol/l. conversely a two fold significant increase was measured during cpb with the patrol method: ti: . ± . ; t : . ± . *; t : . ± . au. *p \ . versus t .conclusions. oxidative stress due to overwhelming release of reactive nitrogen/oxygen species (rn/os) is held largely responsible for sepsis-induced organ failure and mortality [ ] . up-front and/or ongoing distortion of the pro-oxidant/anti-oxidant balance is likely to play an important role in this situation and in ischemia-reperfusion. therefore the patrol test which appeared to be more sensible than the randox tm method could a good tool in these cases and for evaluation of new anti-oxidant treatments in critical care medicine. these results have to be confirmed in a larger population. introduction. sepsis is the leading cause of death in critically ill patients. despite attempts to improve standardized strategies in resuscitation and treatment of sepsis, the morbidity and mortality remain unacceptably high. early diagnosis and stratification of the severity of sepsis is the key to start timely the appropriate treatment. sepsis is the systemic inflammatory response syndrome to infection; it can lead to hypoperfusion and organ dysfunction and at the cellular level to aerobic mitochondrial dysfunction. lactate is the product of anaerobic metabolism and thus may serve as a prognostic factor in this subset of patients.objectives. the authors propose to test the association of the first serum lactate at hospital admission with shock and icu mortality in patients with community-acquired severe sepsis. during the study period , patients were admitted in the unit, of those ( %) had severe community-acquired severe sepsis (cass). crude icu mortality rate among cass was %. considering the model previously described in methods and when the variables were adjusted only gender, age, saps ii, severity of sepsis and serum lactate were retained in the final model for icu mortality and saps ii nad serum lactate for shock (see table ). a first blood lactate level was independently associated with shock and icu mortality in patients community-acquired severe sepsis admitted in intensive care. objectives. the objective of this study was to test whether svo can predict fluid responsiveness in these patients. we studied patients who were monitored with a pulmonary artery catheter for severe sepsis and septic shock. hemodynamic measurements were obtained before (baseline values) and after a fluid challenge with colloids or crystalloids. responders were defined as those with a[ % increase in cardiac index (ci). no additional interventions were performed during the test. student's t test and linear correlation were used for the statistical analysis.results. mean patient age was ± years and the mean sofa score ± . mean arterial pressure was ± mmhg, cardiac index . ± . l/min/m , pulmonary artery balloon-occluded pressure ± mmhg, and heart rate ± bpm. thirty-four patients ( %) responded to the fluid challenge. responders and non-responders had similar baseline svo ( ± vs. ± %, p = . ). baseline svo was[ % in responders ( %) and in non-responders ( %). there was no correlation between changes in ci (%dci) and the baseline svo (fig. ) . sepsis is a disorder of microcirculation [ , ] . although the pathogenesis of microvascular dysfunction in sepsis is extremely complex, neutrophil activation and their interaction with endothelial cells are considered central features of sepsis-induced microcirculatory alterations. to our knowledge, however, no study evaluated the microvascular pattern of septic patients with chemotherapy-induced severe leukocytes depletion.objectives. to assess early microcirculatory response to sepsis in patients with and without drug-induced neutropenia.methods. demographic and hemodynamic variables together with sublingual microcirculation recording (ops-sdf videomicroscopy) were collected in four groups of subjects: septic shock (ss, n = ), septic shock in neutropenic patients (nss, n = ), neutropenia without inflammation (neutr, n = ) and healthy controls (crtl, n = ). except for controls, all measurements were repeated after complete resolution of septic shock and/or neutropenia (tp ). collected video-files were processed using appropriate software tool and semi-quantitatively evaluated (functional capillary density, fcd (cm/cm ); mean flow index, mfi [ ] ) [ ] . conclusions. microvascular derangements in sepsis did not differ between non-neutropenic and neutropenic patients. surprisingly, neutropenia per se without measurable systemic inflammation was also associated with alterations of the sublingual microcirculation. although we cannot exclude the role of residual neutrophils, our data could indicate that leukocytes are not the only and exclusive modulators of septic microvascular dysfunction. in addition, the role and mechanisms of microvascular changes associated with chemotherapyinduced neutropenia warrants further investigation. multiple organ failure is a leading cause of death in critically ill patients. improvements in outcome will most rely on our capacity to measure rapidly accessible biomarkers.objectives. to investigate if the time sequence of reactive oxygen metabolites (roms) production with sofa score could be prognostic for outcome. the study included critically ill patients (from september to december ) who had roms measured (hydroperoxides) during icu stay, when the diagnostic criteria for sepsis (observed n = ), severe sepsis (observed n = ) and septic shock (observed n = ) were present, - days and weeks after the diagnosis (samples n = ); on the same days, the sofa score was calculated. the plasma roms values were assayed by a diacron-italia kit, applied to an automatic instrument (olimpus au ). statistical analysis was performed used mann-whitney test and the linear regression analysis. the roms values and sofa score were inversely correlated (r = . for sepsis; r = . for severe sepsis; r = . for septic shock). the droms (the difference between the first and the last measurement of roms levels in each individual patient) was significantly different between survivors and non-survivors. clinical characteristics of the patients are presented in table . values are presented as median and interquartile rangers. a p value . was considered as statistically significant.conclusions. the plasma roms values decreased when the critically conditions rapidly evolved towards organ failures with higher sofa. to explore: (a) stress neuropeptides (acth, cortisol, prolactin, neuropeptide y (npy) and substance p (sp)) in critically ill subjects and controls, (b) potential association between levels of stress neuropeptides, disease severity and pain. a prospective correlational study, with repeated measurements and cross-sectional comparisons. fifty-three critically ill patients with diverse primary diagnoses and -age and gender-matched healthy controls were studied for days. serum neuropeptides were quantified by elisa (npy, sp) and chemiluminescence immunoassays (acth, cortisol, prolactin). pain levels were assessed by payen and puntillo scales. clinical severity was quantified by multiorgan failure scoring system (mof) and the multiple organ dysfunction score (mods). results. we observed: (a) statistically significant differences between critically ill and control subjects in regard with cortisol (p \ . ), npy (p \ . ) and sp (p \ . ) levels throughout the study. specifically, cortisol levels were higher and npy and sp levels were lower in patients compared to controls, (b) significant bivariate associations between stress neuropeptides (p \ . ), (c) statistically significant associations between acth and pain intensity levels assessed by payen (r = . , p = . ) and puntillo (r = . , p = . ) scales. there was also a constant but not statistically significant (p = . ) trend for lower sp levels in patients receiving opioids than in controls. moreover, npy levels were significantly lower in patients receiving analgesia (p = . ), (d) lower acth and cortisol levels in survivors (p \ . ) (e) at the day of least severity, a significant association between sp levels and mof was observed (r = . , p \ . ).conclusions. (a) despite the fact that npy and sp are stress neuropeptides, their levels appear to be decreased in mods patients. it is worth-exploring whether critical illness may be a state of suppressed activity of some neuropeptides, (b) the observed association between stress neuropeptide levels and survival in critical illness needs to be explore further, (c) bedside measurement of selected neuropeptides in the future may provide an estimation of pain in uncommunicative patients.hence, the study of stress neuropeptides may provide new insight for the management of the critically ill. objectives. the objective of this study was to compare septic and non-septic inflammatory process in critically ill patients with respect to paraoxonase activity, lipid profile and lipid peroxidation markers. methods. analyzed were serum paraoxonase activity, lipid profile, oxidized low density lipoproteins and conjugated dienes in critically patients with sepsis n = ), age/sex/ap-acheii matched critically ill controls with non-septic sirs (n = ) and age/sex matched outpatient controls without inflammation (n = ).results. the activity of pon was lower in septic patients ( . ± . u/ml) as well as in patients with non-septic sirs ( . ± . u/ml) compared to healthy controls ( ± . u/ml). the decrease in paraoxonase activity, high density lipoprotein cholesterol and apolipoprotein a- concentrations was closely followed by the counter increase of serum amyloid a in both groups of patients. there was no difference in paraoxonase activity between septic and non-septic critically ill patients. the concentration oxidized low density lipoproteins and conjugated dienes as markers of lipid peroxidation, were raised in both septic and non-septic sirs critically ill patients as compared with healthy controls. however there was no difference between both critically ill patient groups.conclusions. the decreased activity of paraoxonase in negative correlation with lipid peroxidation markers offers a potentially useful nonspecific marker of inflammation in critically ill patients.grant acknowledgment. objectives. in the present study, we studied the short-term and direct effects of ivig with sepsis.methods. patients was investigated. following the administration of g of ivig for h, we took blood samples immediately following ivig treatment and at h after ivig treatment. blood samples taken at h and just prior to ivig administration were used as controls. while there was no difference between h before and just prior to ivig treatment, statistically significant decreases were observed in the levels of il- after the administration of ivig. no significant changes were observed in the levels of tumor necrosis factor-a and high mobility group box- .changes in serum tnfa, il- , hmgb we confirmed the results of previous animal studies. while we reported that the administration of ivig directly reduces the levels of il- in patients with sepsis, a further prospective study of the ant-cytokine effects following ivig treatment will be conducted in the near future. objectives. to investigate the levels of nucleosome in septic patients and to determine whether nucleosome could serve as a biomarker for sepsis. sixty-four consecutive patients who were newly admitted in surgical intensive care unit at two university hospitals were enrolled in this study. whole blood samples were drawn within h of admission and on the third, fifth and seventh days. a last blood sample was drawn after recovery at icu discharge in survivors or at imminent death in the cases of non-survivors. plasma levels of nucleosome as well as cytokines il- and il- were detected by means of enzyme linked immunosorbent assay. . fifty patients were diagnosed as sepsis and the other fourteen patients were classified as controls. plasma levels of nucleosome were significantly higher in septic patients than in controls (two-way anova, p \ . ), while the levels of il- and il- were comparable between septic patients and controls. the septic patients presented the highest levels of nucleosome on the admission day, which was significantly different from the admission levels of nucleosome in controls ( . ± . vs. . ± . , p \ . ). the plasma levels of nucleosome between survivors and nonsurvivors showed no statistical significance.conclusions. plasma levels of nucleosome may serve as a valuable biomarker for sepsis.introduction. high mobility group box protein (hmgb- ) is a cytokine that can mediate inflammatory response in different conditions included rheumatoid arthritis, infections, sepsis and septic shock. hmgb- released by activated macrophages/monocytes acts as a late mediator of sepsis. studies have shown that serum hmgb- concentrations were elevated in patients with severe sepsis.objectives. in the present study, we evaluated the role of the hmgb- levels at the time of admission at the intensive care unit (icu) as predictor of outcome in patients with sepsis and septic shock.methods. forty-four patients admitted to the icu with sepsis and septic shock was recruited. serum samples were obtained at the time of admission for the determination of hmgb- levels. the results were correlated with the origin of sepsis, severity, organ dysfunction, requirements of mechanical ventilation and vasoactives, days at the icu, comorbidities and mortality at the icu and days after admission. twenty-six patients were male ( . vs. . %). septic shock was present in patients ( . %). the mortality rate at the icu was . % (n = ) and . % (n = ) at day th. hmgb- levels were . ng/ml ± . ( . - . ng/ml). hmgb- levels were significantly higher in non-survivors at the icu than in survivors ( . ng/ml ± . vs. . ± . , p \ . ). higher levels of hmgb- in serum at the admission were correlated with a higher mortality rate in the icu (p \ . ) but not at day th (p = . ). these levels were not correlated with days at the icu, requirements of vasoactives, mechanical ventilation, and apache score.conclusions. the determination of hmgb- levels at admission at the icu in patients with sepsis and septic shock is a good predictor of worse outcome and lethality.introduction. recent experimental and clinical data ( , ) support the hypothesis that costimulatory molecules, such as cd , play an essential role in the innate immune response during sepsis. expression of cd on the surface of monocytes could represent an important pathway in the modulation of the production of several key inflammatory mediators.objectives. to investigate whether the expression of cd molecule on the surface of plasma monocytes differs among the various stages of sepsis. a total of participants ( icu patients with sepsis, icu patients with septic shock and healthy controls) were included in the study (male patients . %, mean age . ± . years). inclusion criteria: icu patients on mechanical ventilation with first episode of sepsis or septic shock during current hospitalization. exclusion criteria: immunosuppression, neoplasia, autoimmune disease, cardiovascular disease. age, gender and comorbid conditions were recorded. a blood sample for quantification of cd expression was obtained at the time of enrollment (day ), and on the fifth day after the onset of sepsis; measurement was made on the same day. cd expression on the surface of plasma monocytes (on days and ) was assessed by flow cytometric analysis. statistical analysis: kruskal-wallis test to identify difference of cd expression among the groups was performed. post-hoc analysis was made by mann-whitney u test between independent groups, using bonferroni correction for multiple comparisons. roc curve analysis was used to determine the accuracy of cd in identifying patients with sepsis or septic shock. patients with sepsis had significantly higher levels of cd (day ) compared with healthy controls subjects ( . ± . vs. . ± . , p b . ). on the contrary, patients with septic shock did not show any significant difference compared with controls. a roc curve analysis for cd (day ) (auc = . , p b . ), revealed that a cut-off value of . could predict patients with sepsis with a sensitivity of % and a specificity of %.conclusions. upregulation of cd expression may reflect a protective phenomenon during sepsis. on the contrary, low cd expression could represent impaired immune function associated with more severe disease. in order to increase the cardiac output in the septic shock patients, according to surviving sepsis campaign team, norepinephrine (ne) or dopamine administration was recommended. the both agents increase the sympathetic tone which antagonize against parasympathetic activity used for gastrointestinal motility (involved gastric emptying). then, it is raised a question whether ne delayed the gastric emptying or not.objectives. this study was aimed to evaluate the gastric emptying in the septic shock patients with norepinephrine. a prospective observational study involved adult septic shock patients, who received ne continuously in icu sardjito general hospital (yogyakarta, indonesia). patients with any head pathologies (trauma, surgical procedures for tumor or bleeding), any gastrointestinal or abdominal pathologies (diarrhea, trauma, surgical procedures for cancer, peritonitis, ileus etc.), and administrations of metochlopramide or alinamin were excluded. nutrition fluids ( ml) was given passively via nasogastric tube, then after min the tube was aspirated. the volumes of aspirates were recorded in % as a gastric residue. once measurement was done with time randomly for every patient. at the measurement time were recorded the dose of ne and the vital signs.results. the gastric residues were . ± . % ( patients), . ± . % ( patients) and . ± . % ( patients) for the doses of ne of . , . and . lg/kg b.w./ min respectively. at the ne doses of . , . and . lg/kg b.w./min, all of the gastric residues were zero ( patients). the correlation between the ne doses and the gastric rescues was statistically significant (p: . ). the mean arterial pressures (map) were . ± . mmhg (ranges from to mmhg. there was no significantly correlation between map and the gastric residues.conclusions. the gastric emptying in the septic shock patients was not disturbed by administration of ne. introduction. anemia is a frequently encountered problem on the intensive care unit. several factor lead to anemia, among which are traumatic blood loss and the drawing of blood for routine laboratory tests. it's not known how this may affect innate immunity. hepcidin is a central regulator of iron homeostasis. it is induced in response to iron and inflammation and reduced in response to anemia and hypoxia. the suppression of hepcidin leads to the internalization and degradation of the iron exporter ferroportin on intestinal cells and macrophages, leading to the uptake of iron from the gut and the release of iron from the macrophages from the reticulo-endothelial system (res). these cells are central to the innate immune response and the altered iron status of these cells due to suppression of hepcidin may affect the inflammatory response of these cells. we tested the hypothesis that phlebotomy in human volunteers would lead to a suppression of the innate immune response. this abstract provides data of a pilot study carried out in subjects. to investigate the effect of phlebotomy on the innate immune response of whole blood in human volunteers.methods. three volunteers were subjected to the letting of ml of blood by phlebotomy. blood for the determination of hemoglobin and iron parameters, leucocyte count and differential, and hepcidin- was drawn at day , and after phlebotomy. further whole blood stimulation was carried out at each time point by adding . ml heparin anticoagulated whole blood to a prepared tube containing endotoxin, pam cis or rpmi as a control. final concentrations of lps and p c were ng/ml and lg/ml respectively. these tubes were incubated at °c for h and centrifuged for min at , g. the supernatant was frozen at - until the measurement of tnf-alfa and il- by elisa. cytokine production was corrected for the number of monocytes present. data are expressed as mean ± sem. hemoglobine decreased from . ± . mmol/l at baseline to . ± at day . it returned to normal at day . there were no apparent changes in serum iron levels. there was however a clear decrease in serum ferritin levels from ± at baseline to ? at day . leucocyte count and differentiation did not show any significant changes. hepcidin was clearly suppressed from to day after phlebotomy (from ± to ± ). tnf-alfa production dropped from to ng/ monocytes at day . il- production dropped from to ng/ monocytes. hepcidin levels correlated well with cytokine production (r . for tnf-alfa, r . for il- ).conclusions. phlebotomy leads to suppression of the innate immune response in whole blood. this could be a result of the intracellular decrease of iron in immune cells due to the systemic suppression of hepcidin. these findings are relevant to critical care patients that are subject to the repeated drawing of blood while their immune system is often compromised. introduction. hypothermia and hyperthermia occur in many pathological states presenting to the emergency department. both these processes are known to significantly impair coagulation pathways but as yet there is little evidence to show what affect they have on the evolving clot structure. previous studies have attempted to determine the effect of temperature on whole blood coagulation using techniques such as thromboelastometry (teg) but its ability to provide meaningful outcomes in terms of clot quality and structure remains elusive. recent studies have highlighted the potential of a new technique, gel point (gp) and fractal dimension (d f ), as a functional biomarker in haemostasis. to explore both the changes in coagulation pathways and their associated effect on clot structure and quality based on the new biomarkers, gp and df. following full ethical approval, healthy whole blood samples were obtained from individuals and tested at temperatures of °c (n - ), °c (n - ), °c (n - ), °c (n - ), °c (n - ). an oscillatory shear technique [ ] using an ar-g instrument (ta instruments) was applied to each sample. the gp, which indicates the formation of the fibrin network, was obtained for each sample using the chambon-winter gel point criterion [ ] . this method provides the basis from which d f can be determined [ ] to interpret the structural properties of the clot network. the results were compared with the standard teg analysis. firstly, results showed a significant progressive change in the clot structure by this new biomarker across the whole temperature range ( - °c). secondly, it also highlighted a significant and meaningful correlation between coagulation pathway change (time to gp, tgp) and the eventual clot outcome (fractal dimension). the tgp of the incipient clot was prolonged and the corresponding d f decreased with reduced temperature values. although, the changes in the coagulation pathway of the teg (r time) and the rheometer (tgp) correlated, the new biomarker, d f , provided additional structural data on the fibrin network formed and highlighted the relationship between coagulation pathway changes and the eventual fibrin clot structure.conclusions. in this study, we describe and quantify for the first time how temperature affects the coagulation pathways and how this impacts on the fibrin clot network, morphology and strength by using the new biomarkers, gp and d f . the potential of these new biomarkers in determining the effects of temperature change in critical illness and injury needs to be evaluated clinically. key: cord- -v z jq authors: rajagopal, keshava; keller, steven p.; akkanti, bindu; bime, christian; loyalka, pranav; cheema, faisal h.; zwischenberger, joseph b.; el banayosy, aly; pappalardo, federico; slaughter, mark s.; slepian, marvin j. title: advanced pulmonary and cardiac support of covid- patients: emerging recommendations from asaio—a “living working document” date: - - journal: asaio j doi: . /mat. sha: doc_id: cord_uid: v z jq the severe acute respiratory syndrome (sars)-cov- is an emerging viral pathogen responsible for the global coronavirus disease (covid)- pandemic resulting in significant human morbidity and mortality. based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. we review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of covid- ; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from asaio. of note, this is a “living document,” which will be updated periodically, as additional information and understanding emerges. the human environment is surrounded by a myriad of viruses, the number, and type increasingly being defined. many viral species result in serious, if not fatal infections, e.g., marburg, hanta, ebola, although typically remaining contained to specific hosts, circumstances of infections, or geographies, limiting modes, and extent of spread. [ ] [ ] [ ] of viral species, respiratory viruses, in particular, have periodically presented with widespread distribution of virus resulting in pandemics, with often overwhelming morbidity and mortality. , we presently face such a situation with the emergence of the severe acute respiratory syndrome (sars)-cov- virus. [ ] [ ] [ ] the major viral pandemics of the last century, including those involving h n and h n influenza and sars-cov and middle east respiratory syndrome (mers)-cov coronavirus, predominantly manifested as respiratory system illnesses with possible secondary cardiovascular and other end-organ system effects. although many patients develop a mild to moderate illness, a significant subset of patients develop severe progressive respiratory and occasionally cardiac failure, refractory to conventional therapies, including advanced ventilator management strategies. for these patients, the only plausible treatment strategy is artificial lung or circulatory support. from the initial clinical experience in china and in italy, it is clear that sars-cov- infection, also termed coronavirus disease , that is covid- , has a disease natural history that results in severe respiratory and circulatory compromise for a significant portion of those infected. it is the specific goal of the present paper to provide a resource document to the clinical community regarding evolving best practice strategies for advanced pulmonary and cardiac support in patients with severe progressive covid- . overall, the philosophy of the present paper is to be a living document-one gathering best practice information of the moment, which will be rapidly and continuously updated as improved strategies emerge. we first provide a brief background on the biology and pathophysiology of covid- infection, evolving modes of diagnosis, and valuable laboratory parameters to follow. we provide evolving information on medical therapies. we then focus on management of the severely compromised patient warranting artificial lung or circulatory support. recommendations are offered for patient selection and details of appropriate therapeutic pulmonary or cardiac support. covid- is the result of infection with sars-cov- , a novel coronavirus, causing severe acute respiratory syndrome. , , covid- is considered a zoonotic infection, with a natural reservoir most likely in bats, and with a potential intermediate species before the onset of human infection. , at the time of this writing, it is unclear how human transfer occurred. moreover, if or when mutations have occurred in sars-cov- , it is unknown whether these may have occurred within nonhuman animal reservoirs, or following human transfer. recent studies, however, now point to pangolin species as a natural reservoir of sars-cov- -like covs. sars-cov- is a single (+) stranded rna virus whose replication is catalyzed by an rna-dependent rna polymerase. however, genomic single-stranded rna also has messenger rna function, such that it may be translated on ribosomes into a peptide sequence. similar to the original sars virus, also a coronavirus, sars-cov- is capable of binding cell surfacebound angiotensin-converting enzyme (ace ), which is richly expressed on pneumocytes, as well as endothelial cells. , this interaction facilitates viral intracellular entry. in addition, the viral spike protein has a polybasic cleavage site at a location between the spike subunits, which may be proteolytically cleaved; this is thought to enhance viral entry and infectivity. , infection with sars-cov- results in the development of acute pneumonia, with patchy ground-glass opacities. the distribution of this infiltrate appears to be more dominant in lung bases, and is eccentric, with an emerging pattern. this pattern may be appreciated via direct example shared on line. this is a near-universal (> %) finding in hospitalized patients with covid- , based upon data from the original patient cohorts in wuhan, china. however, clinical manifestations may be quite variable. fever is a near-universal finding. however, although dyspnea is a common finding both in intensive care unit (icu)-hospitalized as well as non-icuhospitalized patients, it is unsurprisingly significantly and substantially more common in icu patients. in addition, constitutional symptoms such as anorexia are more common in icu patients. acute hypoxemic respiratory failure of varying severity is the norm in icu patients. a median p a o /f i o ratio of < was identified in icu-hospitalized patients, and ratios were worse in non-survivors in comparison to survivors. the documented incidence of acute respiratory distress syndrome (ards) was ≈ %. biochemical evidence of myocardial injury was present in ≈ % of patients; further, overt shock was evident in < % of patients. as expected, ards and shock were more common in icu-hospitalized patients. systemic arterial blood pressure did not appear to relate to survival; however, inotrope/vasoconstrictor usage was substantially higher in icu-hospitalized and non-survivor patients. moreover, the hemodynamic profiles of shock in these patients are unclear. finally, as is common in other etiologies of shock and respiratory failure, dysfunction of other end-organs, such as the kidney and the liver, was found to be more common and more severe in icu-hospitalized and non-survivor patient groups. in particular, acute kidney injury and its severity were highly correlated with poorer outcomes. laboratory data consistent with higher-risk covid- subgroups were identified as well. icu-hospitalized patients and non-survivors tended to have overall leukocytosis yet with lymphopenia, coagulation profiles consistent with disseminated intravascular coagulation (elevated prothrombin time and d-dimer), elevated blood urea nitrogen and creatinine, elevated serum transaminase levels, and elevated procalcitonin. , these findings are broadly consistent with those of high-risk subsets of sepsis. many fail to appreciate the degree of isolation and care that chinese medical institutions provided their early patients. they were experienced with the sars epidemic and applied that experience early in the spread of the disease. likewise, the medical sophistication of italy appears underappreciated in the lay press. the italian setup mostly focused on large hospitals with icu preparedness, lacking a comprehensive plan on community medicine and small healthcare institutions. indeed, the first patient was diagnosed in a small city, codogno. following this, a "red zone," with total limitation of social mobility, was instituted for containment of infectious spread. the case was particularly challenging since this patient was a young healthy athlete without any medical or epidemiological (travel to china or contact) risk factors. the first case immediately prompted the development of a task force for managing and limiting the outbreak on a regional level. the united states is early in its experience with covid- , but has per capita fatality rates that are, along with germany, the lowest of those countries afflicted with a large burden of infected patients. the early german public health experience with covid- is particularly noteworthy for the lowest mortality outcomes within the group of infected patients, but the reasons for this are unclear at this time. unpublished communications suggest that this may be due, at least in part, to a younger covid- -infected population. covid- infection manifests with symptoms typically associated with other respiratory infections, that is, fever, cough, and shortness of breath, which are sensitive but highly non specific. to this end, a basic diagnostic algorithm for "fever clinics," given the high sensitivity of fever as a sign of covid- , has been developed. high-fidelity, sensitive, specific, and predictive diagnostic strategies are needed. it should be noted that current center for disease control (cdc) recommendations reiterate that "clinicians are strongly encouraged to test for other causes of respiratory illness" as appropriate. conversely, covid testing should be employed for those with a high index of suspicion and for those at increased risk. a hierarchy of "priorities of testing" is provided by the cdc. current diagnostic strategies include obtaining samples for viral testing from the upper (nasopharyngeal or oropharyngeal swab or wash) or lower (induced sputum, endotracheal aspirates, bronchoalveolar lavage) respiratory tract samples for via nucleic acid amplification tests, such as reverse transcriptase-polymerase chain reaction; as well as for bacterial or fungal cultures as is appropriate. , confirmation of sars-cov- may be made via follow on nucleic acid sequencing, via detection of the specific n, e, s, and rdrp viral genes. for in-hospital patients, we recommend sending two specimens on two different days to ensure adequate specimen collection. a computed tomography scan of the chest revealing ground-glass opacities or consolidation consistent with the disease increases the clinical suspicion of disease. , basic monitoring includes pulse oximetry and telemetry for stable patients outside the intensive care unit, and more invasive monitoring with systemic arterial and central venous/pulmonary arterial (pa) catheters in the intensive care unit. of note, for inpatients, continued viral detection and shedding has been reported which may also be monitored via blood and stool sampling. , a baseline transthoracic echocardiogram (see following) can be performed if the patient presents with systemic arterial hypotension or overt shock. pa catheter placement may be useful in patients with shock as well (see following). we do not recommend routine endomyocardial biopsies, due to risks of cardiac structural injury (iatrogenic ventricular septal defect, right ventricular [rv] free wall rupture and cardiac tamponade, and tricuspid valve injury with regurgitation). in patients who have evidence of focal/regional cardiac injury, via electrocardiography or echocardiography, diagnostic left-sided cardiac catheterization with coronary angiography is reasonable. ultimately it will be important to monitor if a given patient mounts an immune response and develops protective immunity. while the covid pandemic is just evolving, it is important to mention this here as well. as such, with an eye to the future, early reports examining the serologic response of patients in china reveal that covid patients generally mount a typical serologic response to viral infection. specifically, utilizing elisa, igm has been detected by day with igg levels rising subsequently as igm begins to decline. there are currently no specific therapeutics approved by the food and drug administration to treat this patient population. the only randomized-controlled trial done to date was an open-label trial comparing rotinavir/lotanavir combination therapy to standard of care in patients with confirmed covid- illness. this study included hospitalized patients with treatment with the study drug failing to show difference in time to clinical improvement or mortality. there was a trend towards better outcomes in patients started on the study drug less than days after symptom-onset and met the study's secondary outcome. the number of severely ill patients needing invasive mechanical ventilation was low in this particular trial. further studies are required to determine if this drug is efficacious in patients with severe hypoxemic respiratory failure. remdesivir, an inhibitor of rna synthesis, developed by gilead sciences inc., is currently enrolling patients for three clinical trials on the basis of their previous data which showed promise in animal models for treating mers and sars which are also caused by coronaviruses. favipiravir is a similar antiviral agent under investigation in asia. hydroxychloroquine/chloroquine, reported to inhibit sars-cov- in vitro, is postulated to help with inhibition of viral entry and reduce viral infectivity. although this has been currently universally recommended given absence of strong data for any other drugs, there is currently no randomized-controlled trial that has proven its efficacy. with respect to therapies that are not directly antiviral, corticosteroids have been studied in a subset of patients from wuhan with positive results (hr . , ci, . - ), in a retrospective study cohort of patients. further prospective randomizedcontrolled trials are needed to study this further. tocilizumab, an anti-interleukin (il)- receptor blocking monoclonal antibody, is being studied for patients with cytokine release syndrome. there is limited evidence at present time for this drug. similarly, other anti-inflammatory agents inhibiting il- receptor signaling, such as anakinra (soluble il- receptor antagonist) and canakinumab (anti-il- β monoclonal antibody), are under evaluation. adoptive transfer of sera from recovered covid- patients also is being undertaken in covid- . , this approach was utilized with some success in ebola, sars, and mers, with enhanced efficacy if utilized early in the disease natural history. , conceptually, this technique is logically predicated upon ( ) adequate anti-coronavirus antibody titers and ( ) that these antibodies are disproportionately neutralizing in character. from an immunological perspective, solid organ transplant recipients are a group warranting particular attention and careful therapeutic consideration. consensus presently does not exist as to how to best manage immunosuppressive regimens in the setting of covid- infection. it may be reasonable to use lower levels of immunosuppression in the setting of covid- infection, as is often employed when transplant recipients develop other infections, waged from the perspective of favoring innate immune augmentation. however, as some mortality and morbidity in covid- -infected patients may be due to hyperactivation of adaptive or innate components of the immune system, it may be reasonably hypothesized that maintained or even increased levels of immunosuppression may be beneficial in the setting of covid- infection. as such, we urge caution and careful consideration on an individual patient in addressing this issue. clarity for this issue will emerge as we progress further in the covid pandemic. pharmacotherapies for the cardiopulmonary physiologic effects of covid- are under investigation. anticoagulation is strongly recommended in patients with persistent d-dimer elevation, due to suspicions of an as-yet-to-be-defined prothrombotic milieu in these patients. the role of inhaled pulmonary vasodilators is unclear in the setting of covid- with refractory acute hypoxemic respiratory failure but is being studied. there is no current available guidance regarding the merits of utilizing inhaled nitric oxide, although it could be postulated that this could be helpful in normal compliance ards by reducing hypoxic pulmonary vasoconstriction and improving ventilation-perfusion (v/q) matching, reducing rv afterload. last, with respect to prophylaxis and protection, anti-covid- vaccines are under development by several groups. these include standard peptide/protein-based strategies, as well as rna-based strategies. plans for rapid testing are underway. the need for pulmonary or cardiac support strategies, and the extent of support required, is inversely proportional to the quality of native pulmonary or cardiac function. in addition, the availability of particular types of support equipment is inversely proportional to their invasiveness, complexity, and extent of support required. the broad recommendations below are in line with these concepts. what is proposed as first-line therapeutic strategies generally provide lesser degrees of gas exchange or hemodynamic function support, but are clearly more widely available, and are less complex and less invasive (and thus, less dependent upon operator expertise). however, escalation to second-or third-line therapeutic strategies should not be delayed in favor of prolonged trials of first-line support. decisive determination of whether a strategy is succeeding or failing is essential to achieving optimal outcomes. tables and provide a simple reference guide. covid- results in acute hypoxemic respiratory failure, with severe v/q mismatch and overt intrapulmonary shunting. , the recommendations below are based on previous experience with the management of ards, especially the h n influenza pandemic experience. [ ] [ ] [ ] mechanical ventilation: noninvasive and invasive. noninvasive mechanical ventilation (mv) strategies, such as continuous positive airway pressure (cpap) and bilevel positive airway pressure (bipap), may be appropriate for short durations in patients with hypoxemia suboptimally treated by high-flow supplemental o systems alone. as either a noninvasive or invasive mode of mv, cpap increases basal (throughout the respiratory cycle, and thus evident even at end-expiration, the invasive analog being positive end-expiratory pressure [peep]) intra-alveolar pressure, and thus, lung volume. globally, this may manifest as an improvement from lower-normal to higher lung volumes in the setting of normal overall lung compliance, or in the setting of low overall lung compliance, from lower-to normal-higher lung volumes. mv recruits under-or non-ventilated alveoli that are otherwise yet perfused, and thus improves o transfer of blood flowing past these alveoli, and the overall v/q ratio. bipap, which is analogous to pressure-support invasive mv, provides cpap plus additional input airway pressure during inspiration. this not only increases mean alveolar pressure and volume, but does so by augmenting the inspiratory flow rate, and for a fixed inspiratory time, the tidal volume. noninvasive ventilation (niv) is a reasonable initial strategy in patients with covid- -related respiratory failure, provided that hypoxemia is not profound, and the anticipated duration of niv support is not long. the issue with niv is the need for patient cooperation. there is current concern that cpap and bipap modes may potentiate aerosolization of the respiratory viral particles. some institutional guidelines limit high-flow nasal cannula to < l/min, and avoid niv, due to risk of staff infection, and further suggest that early intubation should be attempted. the timing of such transition from niv to invasive mv presently remains patient specific. a variety of invasive mv modes are available to treat acute hypoxemic respiratory failure. volume-controlled, pressurecontrolled, pressure-support, and mixed invasive mv modes may be best suited for individual patients. based upon data principally best expressed in the ardsnet studies, it is well established that excess pressure and volume each may contribute to pulmonary injury (barotrauma and "volu"-trauma, respectively). , consequently, whether either volume-controlled or pressure-controlled modes of invasive mv are chosen, lungprotective mechanical ventilation should be used in patients with covid- -related acute hypoxemic respiratory failure. this consists in: tidal volumes of < ml/kg ideal body weight, plateau airway pressures of < cm h o, and f i o titrated in order to achieve adequate systemic arterial o saturations. in some patients, paralytic agents may be required. , importantly, individual centers, depending upon availability of invasive and even noninvasive mv, need to make often difficult decisions about resource utilization in the context of potentially more than one individual patient condition. factors in these considerations include severity of gas exchange derangement, individual patient comorbidities, anticipated survivability of the covid- infection, and availability of resources, all must be considered in determination of mv allocation to an individual patient. these issues are even more acute with respect to advanced lung support strategies, as are discussed below. prone position mechanical ventilation. prone positioning is now the standard of care in ards and should be considered in patients with covid- as this would potentially improve lung aeration at the bases of the lung. a prospective multicenter randomized control trial has shown that in patients with p a o / f i o ratio less than mmhg, with an f i o ≥ . , and a peep ≥ cm h o, early application of prolonged prone positioning sessions significantly decreased the -day and -day mortality ( % vs. . %, -day mortality; . % vs. %, -day mortality). we recommend that whenever feasible, all patients with severe hypoxemic respiratory failure with covid- ards should undergo either manual or artificial prone positioning, depending upon the resources available. there is a concern that the man-power needed to prone these patients could potentially expose a large majority of staff members to the virus, and this should be taken into consideration before proning. other observations and unique considerations with respect to conventional management. regarding the preliminary experience with covid- which highlighted the discrepancy between gas exchange and lung mechanics (severe hypoxemia with normal compliance) some relevant physiologic and clinical points are noteworthy. first, several groups have (unpublished data) suggested that covid- is associated with microvascular thrombosis in several tissue beds: pulmonary, coronary, and renal. indeed, high d-dimer is associated with increased severity and mortality of covid- , which is indicative of microthrombosis in these arterial/arteriolar/capillary beds. this may a contributory mechanism with respect to why severe hypoxemia is observed in the setting of normal or high lung compliance, since capillary endothelium and alveolar epithelium both may be involved. in addition to hypoxemia, pulmonary vascular microthrombi, when severe, may also contribute to shock. second, because of refractory hypoxemia, most clinicians increase peep. however, high peep may result in alveolar overdistension in the setting of normal or high compliance. high peep also can augment pulmonary vascular impedance (creation of west zone lung; although if this incidentally happened to occur in unventilated lung zones and pulmonary blood flow were better redistributed to betterventilated lung zones, this might ameliorate hypoxemia), and reduce systemic venous return, both of which reduce rv stroke volume and cardiac output (co). conversely, decreased oscillatory lung loading via low tidal volume and distending pressure "lung-protective" ventilation may cause or exacerbate hypercapnia, permissive or otherwise. extracorporeal gas exchange: extracorporeal membrane oxygenation. if invasive mv fails, a decision needs to be made quickly as to whether extracorporeal gas exchange is appropriate. since covid- -associated respiratory failure is hypoxemic in nature, extracorporeal membrane oxygenation (ecmo) is almost certainly the most appropriate extracorporeal strategy (in contrast to extracorporeal carbon dioxide removal). the decision to utilize ecmo, similar to that for mv above, relates to ( ) anticipated benefit (failure of mv to achieve adequate oxygenation, or requirement of traumatic mv settings in order to achieve adequate oxygenation) in the background of organ systems not directly supported or treated by ecmo, ( ) risks (most notably, local cannulation-related complications, and active or biochemical coagulopathy), and ( ) ecmo supply availability and other institutional infrastructure, and ( ) practitioner expertise. in the case of covid- , in particular, but in ecmo deployment in general as well, dysfunction of organ systems other than those that are ecmo-supported (e.g., hematological/immune, renal, hepatic) decreases the anticipated benefit and may even increase the risks of therapy. , ecmo support has well-recognized local cannulation site vascular risks-that is, both ischemic and bleeding. preexisting coagulopathy increases the risks of local bleeding complications but also increases systemic bleeding complications-most ominously, intracranial hemorrhage. additionally, practical considerations, while non-ideal, are real factors that influence the decision to implement ecmo. with respect to recently published literature, ecmo utilization in the setting of covid- respiratory failure has been associated with poor outcomes (hospital survival well below %), although the number of cases has been too small to draw definitive conclusions. most patients reported in the population from china died. more recent data available to us, as yet unpublished, seem more encouraging, although we do not have data on survival to hospital discharge. overall, we believe that in a high mortality scenario such covid- , ecmo would not significantly impact on the global outcome figures, rather should be discussed on a patient-specific individual basis. our suggestion is that the decision to implement ecmo should follow a clear failure of invasive mv, paralytic agents, and prone positioning; however, this assessment should be rapid. the latter of these is to avoid dysfunction or failure of other organ systems, and we further recommend that in light of the pandemic status of covid- and the generalized poorer outcomes of ecmo support when other organ system dysfunction occurs, that ecmo implementation generally should be restricted to those with isolated single organ system (pulmonary) dysfunction who are invasively mechanically ventilated ≤ days. each institution's experience and resources differ, as do the local and regional epidemiology of covid- ; consequently, ecmo implementation in the setting of renal or hepatic failure must be assessed on a case-by-case basis (further discussion regarding institution in the setting of cardiac failure follows later in this document). we also mention emerging early experience to combine ecmo with means of modulating or removing cytokines, as yet a further extension of modalities for the sickest of patients with cytokine storm and severe cardiopulmonary compromise. we now turn to the specific "tactical" aspects of ecmo, focusing on cannulation approaches, since the cannulation approach is one of the few important variables that can be not only controlled, but altered to optimize gas exchange. we initially focus on "right-sided" ecmo used for pulmonary support, that is, ecmo in which the right side of the circulation is exclusively accessed (the most common form of which is veno-venous [v-v] ecmo). tables and provide a summary. central versus peripheral. central cannulation, that is, of the great vessels and generally via an open surgical approach, has the advantage of providing large cannula, with low resistance and high maximal volumetric flow rates. however, it is invasive and has greater periprocedural (not necessarily longer-term, though) bleeding risks. moreover, central cannulation requires cardiothoracic surgeons to perform it. peripheral cannulation generally cannot achieve the fluid mechanics of central cannulation. however, peripheral cannulation is most commonly percutaneous and has lower periprocedural bleeding risks. finally, practitioners of a variety of specialties can be trained to perform peripheral cannulation procedures-i.e. cardiothoracic surgeons, interventional cardiologists, critical care anesthesiologists, and icu physicians. although central cannulation is hemodynamically advantageous (with respect to higher flow rates; hemodynamic support is not relevant in pure v-v ecmo), in light of its invasiveness, bleeding risks, and specialized training required, it is more reasonable to propose peripheral cannulation as the initial approach of choice for covid- -related respiratory failure. percutaneous: single versus two cannula. for right-sided ecmo, either single cannula (dual-lumen) or dual cannula approaches exist. advantages of the single cannula approach include reduced risks of local bleeding complications and the potential to ambulate. in the case of right atrial/ventricular inflow and pulmonary arterial outflow, lesser degrees of recirculation are present. this latter single cannula approach also provides rv mechanical circulatory support (mcs) (see below). however, overall volumetric flow rates may be lower, and image guidance during cannulation is necessary. in contrast, the two-cannula approach requires two venous cannulation sites and typically precludes the ability to ambulate. moreover, recirculation is common, although it may occur with the single cannula approach if both inflow and outflow are in the systemic venous compartment. however, higher flow rates are achievable with the two-cannula approach, and image guidance-which often is not present under emergent circumstances-usually is not needed. the lack of need for image guidance means that unlike the single cannula approach, cannulation using the two-cannula technique does not require operating room or catheterization laboratory environments, and potential covid- exposure of these vital spaces and their ancillary staff. thus, we suggest that the two-cannula technique should be preferred for most institutions and circumstances. bi-femoral approaches are particularly advantageous in terms of rapidity of deployment, avoidance of cannulating surgeons and physicians being positioned near the patient's oropharynx and endotracheal tube, and ease of subsequent prone positioning. however, under the current circumstances, we recommend each team use whatever cannulation technique is most familiar and comfortable, to minimize complications. some patients with covid- develop shock. , the hemodynamic profile of shock (cardiogenic versus distributive versus hypovolemic), and its coexistence or lack of coexistence with respiratory failure is unclear based upon the available published literature. it is possible that, in highly selected and limited cases, mcs with or without pulmonary support may be appropriate. [ ] [ ] [ ] in particular, decision-making regarding implementation of left ventricular (lv) support is complex (see below). these strategic and tactical issues related to mcs in covid- -infected patients are reviewed. when (if at all) should mcs be used in the setting of shock in covid- . based upon the existing data, it is unclear whether shock occurs in a subset of hospitalized covid- infected patients with respiratory failure, or whether it may occur independent of respiratory failure. unpublished communications to us suggest that shock occurs in a small but noteworthy (due to their dire clinical status) subset of covid- patients with respiratory failure requiring at least mechanical ventilation. because outcomes are clearly poorer when more organ systems are dysfunctional, we suggest that mcs ought to be highly selectively implemented in covid- -infected patients. yet, some patients, particularly those who are relatively younger, with fewer underlying comorbid conditions and good overall short-and long-term life expectancy, may be appropriate candidates for mcs. given the range of clinical profiles in patients with covid- , we recommend early adoption of an interdisciplinary approach, incorporating advanced heart failure specialists, a lesson learned from ongoing efforts in the arena of complex cardiogenic shock. , the immediate discussion is restricted to the left-sided circulation because decision-making here is even more complex. it is first important to determine whether left-sided cardiac dysfunction is present. in patients with shock, echocardiography (see following discussion) is particularly useful, and pulmonary arterial catheters are helpful as well, both for blood flow measurements as well blood gas measurements from different circulatory compartments. underlying congenital or acquired structural or coronary arterial disease is assumed to be absent for the purposes of this discussion. if the systemic arterial blood pressure (mean arterial pressure [map] < mmhg) is decreased, or high doses of inotropic and vasoactive agents are required to achieve a normal-range systemic arterial blood pressure, then echocardiography should be undertaken. if the lv ejection fraction (lvef) is at least moderately reduced (lvef < %), this is clearly abnormal, and in the acute setting, with a non-dilated lv and normal-range lv end-diastolic volume (lvedv), stroke volume would be substantially reduced. in addition, invasive hemodynamic monitoring assessments, such as those provided by pulmonary arterial catheters, often are helpful in discerning whether intrinsic lv dysfunction is present (lv stroke work may be calculated; see discussion below). however, it is important to note that the lvef is not a good index of intrinsic lv systolic function or true lv contractility because it is inversely proportional to afterload; indices such as prsw are superior, but generally are not feasible to obtain in the clinical setting. the lvef may be reduced if the impedance of the systemic circulation is increased, without decreased lv contractility; however, the systemic arterial blood pressure most commonly is normal-range or increased in such patients (calculations of lv stroke work or power would be required in order to formally assess this), which is not the case in shock. regardless of whether systemic arterial hypotension is thought to be cardiogenic with lv failure, distributive, or mixed, the lvef generally is a useful index to use in order to determine whether mcs is reasonable. if lvef is high or even normal in the setting of systemic arterial hypotension, and the lvedv and heart rate are normal, then the co is normal or elevated, and mcs would have to be able (with native output) exceed that in order to have a hemodynamic benefit. in contrast, if the lvef is low, then for a normal lvedv and heart rate, the co is reduced despite optimal lv preload, and mcs may be reasonable. if the lvef is reduced, and high doses of inotropes are required to treat systemic arterial hypotension, mcs for the lv may be appropriate in highly selected covid- patients. however, with rare exception, shock with a normal lvef (predominantly distributive) should not be treated with mcs, unless volumetric flow rates well in excess of the native co can be achieved. as discussed, although invasive hemodynamic assessment may not be feasible in a timely fashion in patients with covid- whose clinical status is rapidly deteriorating, invasive assessment is the gold standard. if pa catheters can be placed expeditiously in patients with shock, they are recommended for the purposes of definitive diagnostics; from pa catheters, the co and index, lv power/cardiac power output (cpo), as well as pa pulsatility index, may be obtained. as stated earlier, prsw or stroke work index is the gold-standard index for the assessment of lv systolic function, being superior to systolic ventricular elastance measures. , determination of prsw requires a range of lvedvs to be studied, but for a given lvedv, a particular sw may be used as an isolated data point. lv power (cpo) is the closest clinical correlate to sw (being lv work per unit time) and is clinically calculated as map multiplied by co. this is analogous to electrical power, which for a simple circuit with a single battery and resistor is equal to current (flow) multiplied by voltage (pressure difference), or the square of the current (flow) multiplied by resistance (systemic vascular resistance). an important caveat in using cpo is that it is not a per beat assessment, in that heart rate is incorporated. tachycardia commonly observed in the majority of shock may limit decreases in cpo, even when per lv dysfunction is evident on a per beat basis. modalities for support: veno-arterial ecmo, short-term ventricular assist devices. v-a ecmo: central or peripheral. the relative advantages of central versus peripheral cannulation have been discussed above. however, unlike right-sided ecmo, systemic arterial cannulation is employed. ischemic extremity complications are far more common with peripheral arterial cannulation than central cannulation, which reduces the relative advantages of central cannulation. perhaps more importantly, lower extremity arterial cannulation may result in differential hypoxemia when hypoxemic respiratory failure is present, wherein the lv ejects hypoxemic pulmonary venous return into the aortic root/coronary arteries/proximal aortic arch, whereas the lower body is perfused with normoxemic or hyperoxemic postgas exchanger blood flow. consequently, decision-making with respect to central versus peripheral cannulation for v-a ecmo is more complex than for v-v ecmo alone. hybrid v-v/v-a ecmo approaches may be reasonable under such circumstances. however, hybrid configurations are more complex and resource-intensive, typically requiring continuous bedside attendance by a perfusionist or ecmo specialist. short-term paracorporeal left ventricular assist devices with either central or peripheral cannulation; short-term cathetermounted left ventricular assist devices (impella). the principal advantages of left ventricular assist devices (lvads) over v-a ecmo in shock are direct lv unloading, and more homogeneous distribution of blood flow through the systemic arterial circulation. direct (inflow cannula within the left side of the heart, and particularly the lv) lv unloading is more effective in reduction of lvedv, and consequently, lv diastolic and systolic pressures (reduction of systolic pressures being a manifestation of the frank-starling mechanism); this may be advantageous relative to indirect (inflow cannula proximal to/ upstream of the left side of the heart) unloading (e.g., via v-a ecmo) vis-à-vis greater reduction of pathologic load-induced signals and resultant mechanotransduction. it should be noted that the effectiveness of v-a ecmo in unloading the left side of the heart is an area of some controversy. modeling studies suggest that v-a ecmo should consistently result in augmentation of the lvedv and lvedp. however, this is demonstrably not so based upon clinical experience in which lv distension and even subclinical lv volume overload only occur in a minority of cases , as well as recent and even classical controlled animal model studies of v-a ecmo support in acute lv systolic dysfunction. [ ] [ ] [ ] even when lv distension does occur, drainage through a rightsided pa vent catheter can decompress the lv, which runs counter to the aforementioned modeling studies. what is less controversial and clearer, based upon a review of physiologic concepts and the literature regarding lv distension in v-a ecmo, is that mcs approaches which employ left-sided circuit inflow ("direct" unloading) generally are more effective in achieving lv unloading than those which employ right-sided circuit inflow. consequently, in some patients, lvad-based approaches may be superior to v-a ecmo. in addition, when gas exchangers are used in concert, this "modular" approach permits isolated treatment (as well as de-escalation) of cardiac and pulmonary failure. however, these approaches are more technically demanding and require a high level of practitioner and institutional expertise. as is the case for v-a ecmo, we recommend that only highly selected patients with covid- be considered for short-term lvad support. because the impella catheter-mounted micro-axial vads are substantially different from other pump mechanisms insofar as the pump mechanisms themselves are intracorporeal and miniaturized, we briefly mention two salient features. first, percutaneous transfemoral placement may be performed at the bedside under echocardiographic guidance, rather in than in a cardiac catheterization laboratory. in pandemic conditions, this may be useful. second, placement via an axillary artery approach, using the newest iteration of introducer sheaths and securing devices, results in secure pump position, which may facilitate safer prone positioning. with further reference to the range of impella devices, a wide range of delivered volumetric flow rates may be achieved. the original impella . device generally may not provide adequate flow for the severely compromised shock patient for which robust lv mcs is required. the impella cp device is better with a peak flow of . l/m. the impella . and . devices, each of which may be introduced via side-grafts on the axillary artery, are capable of providing flows of . and . l/m, respectively, that is, levels of flow close to those achievable with surgically implanted lvads, all via a minimally invasive platform. finally, secure pump positioning achieved with devices inserted via axillary artery side-grafts has the advantage of longer-term mcs, in patients with slow recovery of lv function. experience with impella in combination with ecmo, that is, "ecpella," to enhance unloading and boost support is just beginning to emerge in severly compromised covid patients. right ventricular support. respiratory failure commonly causes an increase in the pulmonary vascular impedance, increasing rv afterload. in some cases, this can occur to such an extent ("afterload mismatch") that even in the setting of normal intrinsic rv contractility, the rvef and output may decrease substantially (cor pulmonale). in such patients in the acute setting, attempting to treat the underlying etiology of impaired gas exchange using v-v ecmo alone may not be sufficient. this is because v-v ecmo recirculation is exacerbated by reduced rvef and tricuspid regurgitation. in cases of cor pulmonale with covid- -related respiratory failure, we suggest that strategies to support the rv are appropriate. for patients who may require proning, percutaneous rvads using femoro-femoral approaches, can be used with an oxygenator. the single cannula (e.g., protek duo) approach to this offers the advantages of peripheral cannulation via one site, and with minimal recirculation. central approaches may be reasonable in patients in whom high-flow rates cannot be achieved. if high-flow rates are thought not to be achievable with a single cannula approach, then v-v ecmo plus a device such as the impella rp may be reasonable. our asaio recommendations are meant to complement those of the extracorporeal life support organization (elso). the potential role of ecmo, in particular, in covid- is discussed in an overview in lancet respiratory medicine. the elso guidance document: "ecmo for covid- patients with severe cardiopulmonary failure" describes usage of ecmo in covid- patients intended for experienced ecmo centers. although the published small number of patients from china who underwent ecmo had poor outcomes, currently unpublished data from japan and south korea, with ecmo support in + covid- cases, is communicated at ≈ % recovery and survival; however, other locations have communicated equivalent or worse outcomes. accepted ecmo indications, access, and management, are described in the elso guidance for adult respiratory and cardiac failure on the elso web site (elso.org). in general, ecmo is warranted when metrics indicate a high ( %) risk of mortality with conventional management. these notably include p a o /f i o ratio below , despite available optimal care. ecmo used at the time when patients meet indications (not days later) has better outcomes. as mentioned in a recent article by elso leaders in jama, for inexperienced centers, "ecmo is not a therapy to be rushed to the front lines when all resources are stretched during a pandemic." to supplement general ecmo guidelines a covid-specific elso ecmo guidance document has just been published online. a list of experienced ecmo centers is provided on the elso web site. the recommendations below are summarized from the elso report. during the covid- surge, we propose concentrating the sickest young patients in hospitals where experienced ecmo teams are available. because the use of ecmo for covid- is occurring in the midst of a pandemic which can overwhelm hospital resources, important unique strategic issues/questions/considerations for ecmo resource allocation in covid- patients are as follows: should ecmo be considered for covid- patients? this is largely a local (hospital and regional) decision based on overall patient load, other events, and policies in the hospital. if the hospital must commit all resources to other patients, then ecmo should not be considered until the resources stabilize. if the hospital feels that ecmo can be safely provided, then it should be offered to patients based on risk/benefit analyses. understanding hospital resource limitations as above, standard ecmo should continue when that is possible related to overall hospital resources. patients without comorbid conditions under age are the highest priority while resources are limited. health care workers are high priority. standard contraindications apply: terminal disease or otherwise highly limited life expectancy at baseline, active biochemical or clinical coagulopathy (particularly that which is unable to be treated or has failed treatment), major cns damage, do not resuscitate (dnr status), and the absence of consent. exclusions for covid- during limited resources are hospital-specific. because prognosis is worse, patients with major comorbid conditions (of particular note is immunosuppressioneither due to disease or iatrogenically), age > , and mechanical ventilation greater than days, could be reasonably excluded. anecdotally, renal failure is not an exclusion; however, general outcomes with covid- patients with renal failure is exceedingly poor in the published chinese experience. should ecmo during cpr (e-cpr) be considered for covid- patients? due to the complexity and extensive team training associated with doing e-cpr, centers who do not currently provide these services, should not initiate programs during times of limited resources. in ecmo centers, consideration should be given to whether to continue developmental programs such as out of hospital e-cpr or off-site cannulation during resource-limited times. if an e-cpr program is also structured for organ donation and shares these personnel, strict cooperation with the transplant allocation system should be maintained, as covid- status has eventually to be thoroughly assessed and evaluated. what protective measures for the team should be used? standard covid- precautions as recommended by who and national health organizations (e.g., centers for disease control) should be used. there are not special precautions for blood contact. eventually, health care workers who are immune to covid- (post-convalescent, or vaccinated) may not need protection for themselves (although they could be carriers). it has come to our attention that some groups are considering early adoption of ecmo as a potential alternative to mechanical ventilation. we emphasize that v-v ecmo is not an alternative to mechanical ventilation or proning. on a physiologic level utilizing active, appropriate pressure and volume lung inflation, avoiding barotrauma, with low-level peep, is vital to maintain pulmonary alveolar inflation, reduce fluid transudation and attempt to maintain a modicum of innate lung physiology, with an aim towards recovery. v-v ecmo should only be considered when mechanical ventilation is failing. further, from a resource utilization and relative risk perspective, moving to ecmo is a resource-intensive and resource-consuming procedure that should be utilized with careful consideration. to date, survival on ecmo for cardiorespiratory failure is highly variable in covid patients and significantly less than the previously reported % at most centers. how to approach therapeutic futility for termination? during times of limited resources observing no lung or cardiac recovery after days on ecmo can largely be considered futile, and the patient can be returned to conventional management. of course, individual patient decisions must be guided by the overall consensus related to a given patient, in a given clinical context, by the treatment team involved. of note, the "save"-survival after veno-arterial ecmo, scoring system has been developed by elso and the department of intensive care at the alfred hospital in melbourne, to provide estimates of survival for adults undergoing v-a ecmo. however, we caution that this was developed based solely on consideration of patients with refractory cardiogenic shock. as of this writing, no data exists as to its translatable utility in compromised covid patients on ecmo. further, the bulk of compromised patients with covid in need ecmo, with pulmonary dominant needs, will require vv, rather than v-a ecmo, to which save does not apply. the covid- pandemic poses major and possibly unique challenges to physicians and medical institutions. although a limited number of patients may need artificial lung and/ or heart support, these patients are among the most complex and resource-intensive. consequently, it is important to develop pathways for their optimal care. this document is offered by asaio as a starting point of guidance in order to help our community approach these critically ill patients. this document will evolve as our collective experience grows, and as treatment approaches reveal efficacy versus limited success. 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convalescent plasma in ebola virus infection convalescent plasma study group: the effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis vaccine designers take first shots at covid- clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in acute respiratory distress syndrome network. ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome pandemic preparedness and response -lessons from the h n influenza of extracorporeal membrane oxygenation for severe respiratory failure in adult patients: a systematic review and meta-analysis of current evidence brigham and women's hospital covid- clinical guidelines ventilator-induced lung injury salvage therapies for refractory hypoxemia in ards acurasys study investigators: neuromuscular blockers in early acute respiratory distress syndrome treatment of ards with prone positioning proseva study group: prone positioning in severe acute respiratory distress syndrome association of coronavirus disease (covid- ) with myocardial injury and mortality the inflammatory response to extracorporeal membrane oxygenation (ecmo): a review of the pathophysiology six-month outcome of immunocompromised severe ards patients rescued by ecmo. an international multicenter retrospective study extracorporeal membrane oxygenation for coronavirus disease in shanghai covid- respiratory failure: targeting inflammation on vv-ecmo support covid- ) and cardiovascular disease percutaneous mechanical circulatory support for cardiogenic shock advanced percutaneous mechanical circulatory support devices for cardiogenic shock percutaneous mechanical circulatory support devices for high-risk percutaneous coronary intervention standardized team-based care for cardiogenic shock national cardiogenic shock initiative investigators: improved outcomes associated with the use of shock protocols: updates from the national cardiogenic shock initiative linearity of the frank-starling relationship in the intact heart: the concept of preload recruitable stroke work left ventricular distension in veno-arterial extracorporeal membrane oxygenation: from mechanics to therapies mechanical unloading in heart failure incidence and implications of left ventricular distention during venoarterial extracorporeal membrane oxygenation support how small is enough for the left heart decompression cannula during extracorporeal membrane oxygenation? myocardial perfusion and cardiac dimensions during extracorporeal membrane oxygenation-supported circulation in a porcine model of critical post-cardiotomy failure changes in left ventricular systolic wall stress during left ventricular assistance effect of extracorporal membrane oxygenation on left ventricular function of swine left ventricle unloading through pulmonary artery in patients with veno-arterial extracorporeal membrane oxygenation first successful treatment of covid- induced refractory cardiogenic plus vasoplegic shock by combination of pvad and ecmo -a case report mechanical circulatory support devices for acute right ventricular failure planning and provision of ecmo services for severe ards during the covid- pandemic and other outbreaks of emerging infectious diseases preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation initial elso guidance document: ecmo for covid- patients with severe cardiopulmonary failure robert extracorporeal life support organization predicting survival after ecmo for refractory cardiogenic shock: the survival after venoarterial-ecmo (save)-score key: cord- -w ysjf authors: nan title: th international symposium on intensive care & emergency medicine: brussels, belgium. - march date: - - journal: crit care doi: . /s - - - sha: doc_id: cord_uid: w ysjf nan ventriculostomy-related infection (vri) is a serious complication in patients with hemorrhagic stroke. in such patients, diagnosis of vris is complicated by blood contamination of csf following ventricular hemorrhage. we aimed to evaluate the diagnostic potential of white blood cells count (wbc), c-reactive protein (crp), and procalcitonin (pct) to identify vris in patients with hemorrhagic stroke during the time of external ventricular drain (edv) in situ. this retrospective study was conducted at the neurosurgical-icu, university hospital of zurich. a total of patients with hemorrhagic stroke and an external ventricular drain (evd) were admitted over a years period at the icu. of those, patients with vris ("vri"), defined by positive csf bacterial culture and increased wbc in csf (> /ul), and patients without vris and with serial csf sampling ("no-vri") were analyzed. patients with csfcontamination or suspected vri (negative csf cultures but antibiotic treatments) were excluded. wbc, crp, and pct were measured daily. csf was sampled routinely twice a week or by t> °c. for the analysis, mean peak values of wbc, crp, pct during the time of evd in situ were compared between groups (t test). data are expressed as mean with ci %. results: between groups, wbc and crp were similar (wbc: . g/l and . g/ l, p= . and crp: . mg/l and . mg/l, p= . in the group vri and no-vri, respectively) ( figure , panel a and b ). in the group vri, pct was low and significantly lower than in the group no-vri ( . ug/l and . ug/l, p= . in the group vri and no-vri, respectively) (panel c). wbc in csf were similar between groups ( . /ul and . /ul p= . in the group vri and no-vri, respectively). in this study, serum-inflammatory markers were not able to screen patients with vris. their routine measurement should be carefully evaluated. introduction: central nervous system (cns) infections constitute a potentially lifethreatening neurological emergency. patients admitted to the intensive care unit (icu) usually present with a severe disease and organ failure, leading to high mortality and morbidity. we have performed a retrospective analysis during a -year period of patients admitted to a polyvalent icu. clinical, demographic and outcome data were collected to evaluate its clinical impact on the outcome of patients with cns infections. we identified patients with the diagnosis of meningitis, meningoencephalitis and ventriculitis, where the median age was , years (range - ). upon clinical presentation, their most frequent signs were fever ( %), meningeal signs ( %), seizures ( %), and a glasgow coma scale score < ( %). all needed ventilation support and % needed cardiovascular support. a definitive microbiological diagnosis was achieved on patients and antibiotic therapy was adjusted on of them. most common microorganisms were streptococcus pneumoniae (n= ), listeria (n= ) and pseudomonas aeruginosa (n= ) (figure ). other gram negative microorganisms were detected and lead to more adverse outcomes. meningitis was the cause of admission on patients and on a minority (n= ) meningitis was considered to be a secondary diagnosis on patients admitted for other causes (traumatic brain injury, subarachnoid or intraparenchymal hemorrhage, postoperatively of neurosurgical tumor). patients that eventually died had at least one risk factor (age> , immunocompromised due to diabetes, corticotherapy, hiv or heart transplantation). patients admitted to the icu were not so aged, but had some comorbidities and risk factors leading to more uncommon microorganisms, increasing the risk of adverse outcomes. this lead to an increase of mortality: % in the icu and an overall of %. study of selenium levels in unresponsive wakefullness (uws) patients with systemic inflammatory response syndrome (sirs) e kondratyeva , s kondratyev , n dryagina the objective of this study was to evaluate the pharmacokinetics (pk) of levetiracetam (lev) in critically ill patients with normal and augmented renal clearance (arc), and determine if the recommended dosage regimen provides concentrations in the therapeutic range ( - mg/l) [ ] . a prospective observational study was conducted in a tertiary hospital. six blood samples were taken during a dose interval at steady state and lev was quantified by hplc. a population pk study was carried out. statistical analysis was conducted to evaluate the differences in pk between patients with and without arc. the suitability of drug concentrations was also assessed. results: seventeen patients were included, with normal creatinine clearance (crcl) ( - ml/min) and with crcl≥ ml/min (arc). ten patients received mg q h, one mg q h and two mg q h. the data were best fitted to a two-compartment model. figure shows lev concentrations during the dosing interval. mean clearance (cl) was l/h and mean volume of distribution of central compartment (v) was l. interindividual variability was and % for cl and v, respectively. no differences were identified between both groups (p> . ) in pk parameters. no correlation was found between lev cl and crcl. trough levels were below the minimum concentration (c min ) mg/l of the therapeutic range in all patients except . furthermore, between - h % of samples were below the c min . conclusions: administered doses were not able to maintain lev concentrations in the recommended therapeutic range. other dosage strategies, such the extension of infusion time with higher doses, could be evaluated in order to obtain a more favourable profile. no correlation between lev cl and crcl was found. the mechanical properties of muscles such as tone, elasticity, and stiffness are often affected in chronic critical ill (cci) patients. a hand-held device known as the myotonpro demonstrated acceptable relative and absolute reliability in a ward setting for patients with acute stroke [ ] . the technology works on the principle of applying multiple short impulses over the muscle bulk via the testing probe. the aim of our study is to assess the feasibility of objective measurement of muscle tone in cci patients with neurological dynamics and serum biomarkers. the study included cci patients with neurological disorders (stroke, traumatic brain injury, neurosurgical intervention for brain tumors) with more than a -weeks stay in icu. dynamic measurements of the muscle properties were taken on the deltoideus, brachioradialis, quadriceps femoris, gastrocnemius using the myo-tonpro. to identify the leading factor in impaired muscle tone also were measured neurological (s , nse), inflammatory (il- ), bacterial load (pct) biomarkers using elecsys immunoassay and the serum level of microbial metabolites using gc-ms (thermo scientific). results: all patients were divided into groups depending on positive and negative clinical dynamics. significant differences were obtained in parameters characterizing changes in muscle tone of lower limbs -f gastrocnemius (tone) - . vs . hz, r quadriceps femoris (the mechanical stress relaxation time) - . vs . ms (p < . , respectively). some significant correlations between five parameters of muscle tone biomarkers and microbial metabolites were revealed. the results of a quantitative measurement of muscle tone objectively reflect the dynamics of neurological status, which in the future may be promising technique for the personalized approach cci in patients. introduction: changes in hormonal status in patients with unresponsive wakefulness syndrome (uws) remains poorly understood. methods: patients in uws were examined at the period from to . patients ( men) with tbi and patients ( men) after hypoxia. acth, cortisol, tsh, free t and t , sth, prolactin and natriuretic peptide were studied in the period from to months uws. in men, the level of total testosterone, lh and fsh was additionally studied. the obtained data was compared with the uws outcome in - months (crs-r scale assessment). none of the studied hormones of the hypothalamic-pituitary-adrenal axis were a reliable criterion for predicting the outcome of uws. most often and consistently was revealed a tendency of disrupt the rhythm of cortisol secretion, with higher rates in the evening hours. the average value of sth was higher in men with the consequences of head injury who had recovered consciousness than in those who remained in uws. significant decrease in testosterone levels, regardless of age, was found in patients with a consequence of tbi. mean levels of lh were higher in patients with tbi and hypoxia who remained unconscious than in patients who later restored consciousness. the average level of fsh was higher in patients who had recovered consciousness . the increase of natriuretic peptide level was observed both in patients who remained in chronic uws and in those who restored consciousness. no certain endocrine background, characterising this category of patients was found. violations of some hormones secretion rhythms, in particular, cortisol can be considered usual for uws patients, especially in patients with tbi. therapeutic hypothermia has not been used before our research in chronically critically ill (cci) patients. temperature decrease in neuronal cells is a strong signal that triggers endogenic cytoprotection programs using early response genes expression. our goal is to determine influences of craniocerebral hypothermia (cch) on level of consciousness in cci patients. we examined patients with different types of brain injuries. males and females, mean age . ± . . patients were divided into groups: main group - patients (vegetative state (vs) - , minimally conscious state (mcs) - ), comparison group - patient (vs - , mcs - ), groups were equal on main parameters (severity, functional state, comorbidity). patients from main group received courses of cch, duration - minutes, scalp temperature - °С, cerebral cortex cooling up to - o c, session end was without slow reheating period, and session's amount was set -until signs of consciousness recovery. cortex temperature check done noninvasively by using detection of brain tissue emi in shf-range. consciousness recovery in vs and mcs patients controlled using crs-r scale. results: cch sessions significantly increased level of consciousness in vs and mcs patient groups. in vs patients vegetative state increased until minimally conscious state and mcs +, and in mcs group until lucid consciousness (p < . ) (figure ). craniocerebral hypothermia is used in chronically critically ill patients for the first time. our research results demonstrated effectiveness of cch as an additive treatment tool in such patients. this let us optimistically determine the perspective of inclusion of cch method in chronically critically ill patient's rehabilitation to increase level of consciousness. despite the clinical benefit of endovascular treatment (evt) for large vessel occlusion (lvo) in ischemic stroke, space-occupying brain edema (be) represents a common complication during the course of disease. routinely, ct imaging is used for monitoring of these patients, notably in the critical care setting, yet novel and easy bed-side techniques with the potential to reliably predict be without repetitive imaging would be valuable for a time and cost effective patient care. we assessed the significance of automated pupillometry for the identification of be patients after lvo-evt. we enrolled patients admitted to our neurocritical-care unit who received evt after anterior circulation large vessel occlusion. we monitored parameters of pupillary reactivity [light-reflex latency (lat; s), constriction and re-dilation velocities (cv, dv; mm/s), and percentage change of apertures (per-change; %)] using a portable pupilometer (neuroptics®) up to every minutes during the first hours of icu stay. be was defined as midline-shift ≥ mm on followup imaging within - days after evt. we assessed differences in pupillary reactivity between patients with and without be (u-test) and evaluated prognostic performance of pupillometry for development of be (roc analysis). in patients ( women, . ± . years) without be, , assessments were compared to assessments in patients ( women, . ± . years) with be. on day , day , and day after evt, patients with be had significantly lower cvs and dvs, and smaller perchanges than patients without be, whereas lat did not differ between both groups. roc-analyses revealed a significant negative association of cv, dv, and per-change with development of be. conclusions: automated pupillometry seems to identify patients at risk for be after evt. a prospective study should validate whether automated pupillometry harbors the potential to reduce unnecessary follow-up ct imaging. the aim of this preliminary analysis is to detect differences between the qualitative and quantitative evaluation of the pupillary function carried out by doctors and nurses of an intensive care unit (icu) of a tertiary level hospital. secondary purpose is to investigate new indications for the use of pupillometry in a population admitted in icu methods: the study has been conducted (currently in progress) at the intensive care unit and ecmo referral center at careggi teaching hospital (florence; italy). the enrolled patients are adult subjects (> years) with alteration of consciousness defined by a glasgow coma scale (gcs) < , following a primary brain injury and/or the use of sedative drugs. the studied parameters, obtained with neurolight pupillometer ® (id-med, marseille, france) are analyzed, integrated and visual/qualitative evaluation of the pupil function shows a lower reliability if compared to automated pupillometry. the estimated error in the proper determination of photomotor reflex is . % (p< . ). no significant difference is reported between quantitative and qualitative pupillometry in the detection of anisocoria. our preliminary results are compatible with previously reported data [ ] [ ] [ ] , even if there was no difference in anisocoria determination. interestingly, a longer latency period among patients treated with opioids has been observed. other results are still in progress. introduction: due to the dynamic of critical care disease, a rapid bedside, noninvasive and highly sensitive and specific method is required for diagnosis. in this study we set out our experience with trancranial color-coded duplex ultrasound (dxt) [ ] . the dxt study identifies cerebral arteries as well as hemorrhagic phenomenon, hydrocephalus, mass-occupying lesions and midline shift. this is the main difference between dxt and conventional transcranial doppler (dtc) which is a blind study and do not provide any image. descriptive, cross-sectional and observational study from december to june . patients were included. inclusion criteria: neurocritical patients. exclusion criteria: no acoustic window, presence of ultrasound artifacts. data collection was performed. it was used a lowfrequency transducer from . - . mhz with trancranial duplex preset ( figure) . the patterns were defined as normal, vasospasm, high resistance, hypermedia and cerebral circulatory arrest, depending on the cerebral flow velocity, lindegaard ratio (lr) and pulsatility index (ip). results: men ( . %) and women ( . %). average age . ( - ). patients diseases: subarachnoid hemorrhage , traumatic brain injury , av malformation , stroke , hemorrhagic cerebrovascular accident and mass occupying lesions . normal pattern: patients (rel. freq . ). vasospasm: patients (rel. freq . ). high resistance: patients (rel. freq . ). hyperemia: patient (real. freq . ). cerebral circulatory arrest: patient (rel. freq . ) conclusions: dxt should be part of the routine of neuromonitoring, it allows real time images especially useful in unstable conditions. although it will be needed a large amount of patients to be statistical significant, dxt is useful considering a non invasive study, bedside and it allows early identification of different clinic conditions. introduction: embolization of the draining vein during endovascular treatment of arteriovenous malformation (avm) may result in venous outflow obstruction and hemorrhage. anaesthesiologist can use deliberate hypotension to reduce blood flow through avm which may be somehow helpful to prevent this scenario. adenosine-induced cardiac arrest may facilitate the embolization too. the goal of our study was to improve the results of endovascular treatment of avm using adenosine-induced cardiac arrest. methods: after obtaining informed consent patients ( male, female) were selected for adenosine-induced cardiac arrest during endovascular avm embolization. main age was , ± years old. of them were evaluated as iii class asa, as iv. endovascular treatment in all cases was performed under general anaesthesia. propofol, fentanyl, rocuronium were used to induce anaesthesia, then all the patients were intubated and ventilated with parameters to keep etco - mm hg. sevoflurane , - , vol% ( cases) or desflurane vol% ( case) were used to maintain anaesthesia. hemodynamic monitoring consisted of ecg, pulsoximetry, non-invasive blood pressure measurement. onyx or/and squid were used as embolic agents. ct was performed to every patient just after procedure as well as neurological examination. results: adenosine dosage was . - . mg/kg. time of consequent cardiac arrest was - sec. there were cases we administered adenosine for time, in one case we had to administer it twice, in one fig. (abstract p ) . circle of willis and pulsed-wave doppler mode of middle cerebral artery - times and times in one more case as well. hemodynamic parameters recovered without any particular treatment in all the patients. embolization has been performed in all the cases uneventfully. postoperative ct showed no hemorrhage. nobody from investigated group had neurological deterioration in postoperative period. our study shows that adenosine-indused cardiac arrest is not very difficult to perform method and it can be useful during avm embolization. a major risk factor for stroke is atrial fibrillation (af). to treat af anticoagulation is needed. there are now several anticoagulants available. however, a lack of head to head data as well as the absence of accurate techniques makes it difficult to compare them and measure determine there efficacy. stroke is known to produce an abnormal clot microstructure which is a common factor in many thrombotic diseases. this pilot study aims to use a functional biomarker of clot microstructure (d f ) and clotting time (tgp) to investigate the therapeutic effects of different anticoagulants in stroke and af. we recruited patients ( af and stroke & af). two samples of blood were taken: before anticoagulation (baseline) and post anticoagulation ( - weeks) . patients were either given warfarin ( %) or axipaban ( %). d f and tgp were measured and compared before and after anticoagulation. results: warfarin increased t gp ( ± secs to ± secs (p< . )), and decreased d f ( . ± . to . ± . (p< . )). apixaban increased tgp ( ± sec to ± sec (p< . )) but did not change df ( . ± . & . ± . ). interestingly we found that in the apixaban group tgp significantly correlated (p= . ) with blood drug concentration levels. in this study we show that d f and tgp can quantify and differentiate between the therapeutic effects of two different oral anticoagulants. showing that warfarin prolongs clotting and weakens the ability of the blood to form stable clots. conversely apixaban prolongs clotting time but does not affect the bloods ability to form stable clots. this shows the utility of the d f and tgp biomarkers in comparing two different treatment options, something no other current marker has proven able to do. where d f and tgp may prove useful tools in a personalized approach to anticoagulation treatment and monitoring in an acute setting. hospital mortality compared to the model with the original hairscore. patients with poor-grade aneurysm subarachnoid hemorrhage (asah) world federation of neurological surgeons (wfns) grades iv and v, have commonly been considered to have a poor prognosis ( - % mortality). though early intervention and aggressive treatment in neuroicu has improved outcome in the past years, it is controversial because most of the patients left hospital severely disabled. the objective of this study was to investigate the clinical and social outcomes in intracranial aneurysm patients with poor-grade asah underwent different intervention therapies. a single center observational registry of poor-grade asah consecutive patients, defined as wfns grades iv and v, treated at tertiary chilean referral center from december to march were enrolled in this study. the clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. clinical outcomes were assessed via gose and and sociooccupational outcome, both at discharge and at months. figure ). % mortality is less than previously reported, and survivors had a favorable recovery, confirmed with neuro psychological test. poor-grade asah patients in our study shows a more positive outcome than previously considered. prognosis of subarachnoid hemorrhage (sah) is scarce, indeed almost half patients die or become severely disable after sah. outcome is related to the severity of the initial bleeding and delayed cerebral infarction (dci). infection and more precisely pneumonia have been associated with poor outcome in sah. however, the interaction between the two pathologic events remains unclear. therefore, we hypothesized that dci may be associated to pneumonia in sah patients. thus the aim of our study was to analyze the association between delayed cerebral infarction and pneumonia in patients with sah. in this retrospective, observational, monocentric cohort study, patients included in the analysis were admitted in neurosurgical intensive care unit or surgical intensive care unit in the university hospital of brest (france) for non-traumatic sah. primary outcome was diagnosis of dci on ct scan or mri months after sah. multivariate analysis was used to identify factors independently associated with dci. a total of patients were included in the analysis (female male ratio / , median age [ - ] years). multivariate analysis was adjusted on sedation, intracranial surgery, fisher classification of sah severity, pneumonia occurrence and non-pneumonia infectious event occurrence ( figure ). pneumonia occurred in patients ( . %) and other causes of infections in patients ( . %). dci was found in patients ( . %). factors independently associated with dci were pneumonia (or . [ . - . ]; p= . ) and non-pneumonia infectious events (or . [ . - . ]; p= . ). interestingly severity table (abstract p ). correlation of safety and efficacy markers of thrombolysis and thrombolysis time with distance from stroke centre results expressed as odds ratio with % confidence interval of initial bleeding evaluated by fisher scale was not independently associated with dci. dci is independently associated with the occurrence of pneumonia or other cause of sepsis. those results may highlight the need for rigorous approach for prevention protocol, early diagnosis and treatment of hospital acquired infectious diseases in sah patients. introduction: traumatic brain injury (tbi) can have devastating neurological, psychological and social sequelae. increased psychiatric morbidity after tbi has been shown in both adult and the pediatric population. also, critical illness as such is a risk factor for psychiatric problems in youth. our aim was to assess risk factors for later being prescribed psychiatric medication in survivors of intensive care unit (icu)-treated pediatric tbi. we used the finnish intensive care consortium (ficc) database to identify patients - years of age, treated for tbi in four icu in finland during the years - . we examined electronic health records and ct scans and collected data on drug prescription after discharge. we used multivariable logistic regression models to find statistically significant risk factors for psychiatric drug reimbursement. we identified patients of which patients received psychiatric drug prescription ( %) during follow up. the median time to prescription was months after tbi (interquartile range [iqr] - months). patients received antidepressants, received stimulants and received antipsychotics. increasing age showed a positive association with all drug prescriptions except for stimulants, where an inverse relationship was observed (table ) . using multivariable analyses, we could not find any admission or treatment related factors that significantly associated with being prescribed psychiatric medications. teenage survivors with moderate disability (glasgow outcome scale [gos] ) showed high numbers of psychotropic drug utilization ( % received any medication, % received antidepressants, % received antipsychotics). our data suggests, that the risk of psychotropic drug prescription after tbi depends on factors other than those related to injury severity or treatment measures. the incidence of drug prescription is especially high in patients with moderate disability. the effects of -adamantylethyloxy- -morpholino- -propanol hydrochloride on the formation of steroid neurotoxicity in rats with brain injury a. semenenko , s. semenenko , a. solomonchuk , n. semenenko depending on the nature of the brain injury and the severity of the victims, mortality in traumatic brain injury (tbi) ranges from to % [ ] . one of the targets for pathogenetic influence on the course of tbi is the use of pharmacological agents that are able to counteract the negative effects of excess concentrations of glucocorticoids on brain. the therapeutic effect of new pharmacological derivative adamantylethyloxy- -morpholino- -propanol hydrochloride (ademol) in rats with tbi was evaluated for days. the pseudoperated animals and control group received . % nacl solution and the comparison group received amantadine sulfate. cortisol levels were used to determine the efficacy of the test drugs in tbi. in rats treated with ademol, the level of cortisol in the blood ranged from to ng/ml (p -p ) and was . -fold lower (p< . ) compared to control pathology group on the day of therapy. instead, the effect of amantadine sulfate on the level of cortisol in the blood was significantly less than that of ademol. the concentration of cortisol in rats with amantadine sulfate in the blood ranged from - ng/ml (p -p ), was . times lower (p< . ), compared with the control pathology group, and by . % (p< . ) exceeded the corresponding value in animals treated with ademol. therapeutic treatment of rats with severe tbi with a solution of ademol, preferably better than rats in the group with . % nacl and amantadine sulfate protect the brain from the formation of steroid neurotoxicity by cortisol (p< . ). although cerebrovascular pressure reactivity (prx) well correlate to patient's outcome [ ] , it requires continuous monitoring and mobile average calculation for its determination. we therefore hypothesized that a simplified model of variation between mean arterial pressure (map) and intracranial pressure icp over the first three days of admission would have been able to predict patient outcome: we call this new parameter cerebrovascular pressure correlation index (cpc). we performed a retrospective observational study of all adult patients with severe tbi admitted to icu from january to april inclusive. all consecutive patients with a clinical need for icp monitoring were included for analysis. both for icp and map data were mean value over -hours registration, for a total of observations/day, cpc was therefore calculated as the pearson correlation coefficient between icp values (x axis) and map values (y axis), obtaining one single value every hours. variables included in the model (i.e. cpc, cpp, icp, systemic glucose, arterial lactate, paco , icp, and internal body temperature) were collected for the first days since trauma. for the main outcome only the minimum value of cpc fit the regression analysis (p = . ). the correspondent roc curve showed an auc of . . the associated youden criterion was ≤ . (sensitivity = . ; specificity = . ). of all the variables considered for the secondary outcome only cpcmin fit the regression model (p = . ). table reports the median and iqr range for sg and nsg of all the variables considered in the model. this observational study suggests that cpc could be a simplified model of variation between map and intracranial pressure icp over the first three days of admission predicting patient outcome. introduction: impaired cerebrovascular reactivity (car) after traumatic brain injury (tbi) is a marker for disease severity and poor outcome. it is unclear how dynamic changes in body temperature and fever impact car and outcome. we calculated the pressure reactivity index (prx) using the center-tbi high-resolution intensive care unit cohort, as a moving correlation coefficient between intracranial pressure (icp) and mean arterial pressure (map). minute and hourly values of prx and temperature were averaged in patients with simultaneous recording of icp and abp. demographic data was based the core registry (v . ). linear mixed models were calculated based on minute-by-minute data using r with lme v . - and ggeffects v . . . generalized estimating equation models were used to analyze changes during effervescence (increase of temperature of > °c within hours). we assessed high frequency physiological data during days of patients admitted to the icu with predominantly a closed injury type (n= / ). median age was years (iqr - ), baseline gcs was (iqr - ), and % had at least one unreactive pupil. the main measurement site for temperature was the urinary bladder / ( %). half of the patients ( / ) developed fever(> h with mean t ≥ . °c) with a total of h fever and a median of h fever(iqr - ) per patient. of effervescence episodes ( %) reached the febrile threshold of . °c which was associated with an increase in prx from . (±sd . ) at baseline ( h before) to . (±sd . ) during the febrile peak (p= . ) (figure -a) . linear mixed models showed a quadratic relationship between prx and temperature (p< . ) with an increase in predicted prx with febrile and hypothermic temperatures ( figure b ). the association of increasing body temperature with worsening of car supports prevention of fever in severe tbi. prospective studies are needed to further differentiate between mechanisms involved (i.e. inflammation) and central autonomic dysregulation. fig. (abstract p ) . the patients with a good -month outcome (gose> ) after severe traumatic brain injury showed an increase in root mean square of successive differences between normal heartbeats (rmssd) (compared to baseline -minutes before tracheal succtioning) acute kidney injury (aki) is relatively common in patients with severe traumatic brain injury (stbi) and it can contribute to morbidity and mortality [ ] . nephrocheck is a point-of-care urine test that flags two biomarkers that indicate if a critically ill patient is at risk for aki. we investigated the incidence of subclinical aki in patients with stbi. we performed a prospective observational study of all adult patients with severe tbi admitted to icu from january to april inclusive. all consecutive patients with a clinical need for icp monitoring were included for analysis. urine samples of severe tbi patients was collected at icu admission from patients to measure nephrocheck (nc) test [igfbp ] x was performed using the nephrocheck® astute ™ meter. serum creatinine was collected at admission, during the first three days, at icu dismission and -days follow up to assess renal recovery. the diagnosis of aki was based on kdigo criteria. hemodynamics, electrolytes, peep, p/f, kind of fluid administered, fluid balance, % fluid overload, length of stay, the sequential organ failure assessment score, injury severity scores and mortality were collected. a total of patients ( %) presented a median nc higher values at icu admission. one patient with positive nc value experienced aki at hrs. the positive nc group had more plasma transfusion (p-value . ) and a lower median hematocrit at hrs (p-value . ), but similar hospital length of stay (p= . ) and mortality rate (p= . ) conclusions: nc at icu admission identifies subclinical aki in tbi patients and it maight be used to predictclinical aki. hemodilution (but not fluid overload) seems to be associated with development of subclinical aki. higher nc at icu admission is not associated with worst longterm outcome in tbi patients. severe traumatic brain injury (tbi) is considered a serious public health problem in europe. partly because of the heterogeneity of tbi, considerable uncertainty may exist in the expected outcome of patients. the international mission for prognosis and analysis of clinical trials in tbi (impact) and the corticosteroid randomization after significant head injury (crash) prediction models are considered the most widely validated prognostic models [ , ] . however, studies using these prediction models for benchmarking of outcomes have been scarce. we aimed to compare actual outcomes in a tbi cohort of critically ill tbi patients with predicted outcomes in a quality of care initiative in an academic hospital. in this retrospective cohort study, we included consecutively admitted tbi patients to the icu adults of erasmus mc, university medical center, rotterdam, the netherlands between january and february . we included patients with tbi. -day mortality was %, sixmonth mortality was % and six-month unfavourable outcome was %. the impact core+ct+lab model predicted % -month mortality (vs % actual, p= . ) and % unfavourable outcome (vs % actual, p= . ). the -day mortality prediction by crash prognosis calculator was % versus actual -day mortality of only % (p= . ), whereas -month unfavourable outcome prediction by crash was % (vs. % actual, p= . ) ( figure ). the impact model, although developed more than a decade ago, seemed appropriate for benchmarking purposes in this single center cohort in the netherlands, while crash predictions were less applicable to our setting. introduction: out of hospital cardiac arrest (ohca) continues to be associated with significant mortality and morbidity. centralisation of care has considerably improved patient survival but has resulted in increased morbidity in the form of neurological deficit. accurate neurological prognostication remains challenging incorporating repeated clinical examination and ancillary investigations [ , ] . data was collected retrospectively and analysed for patients admitted post ohca from october to october . patient arrest demographics were collected in conjunction with extensive inpatient investigation findings including ct, traditional pupil assessment, pupillometry and eeg. results: % of patients survived to hospital discharge. patients presenting in a shockable rhythm continue to have higher survival rates ( table ) . % of patients who received immediate cpr survived to hospital discharge in comparison to % of patients who did not receive immediate cpr. % of patients underwent non-contrast ct head. % of patients had traditional pupillary examination performed on arrival. pupillometry was introduced in december ; out of a possible patients had pupillometry during their inpatient stay. eeg was undertaken in % of cases. our data shows receiving immediate cpr and presenting with a shockable rhythm remain positive prognostic factors. ct head as a stand-alone prognostic modality is unreliable with % of patients who survived to discharge, with intact neurology, had an admission ct head reported as hypoxic brain injury. a new neuroprognostic strategy is required in our unit that adds further certainty to likely clinical outcome. this includes increased use of tests such as eeg and pupillometry and the introduction of biomarkers such as neuron specific enolase, somatosensory evoked potential testing and magnetic resonance imaging. introduction: post-resuscitation care of patients following an out-of-hospital cardiac arrest (oohca) is set out by the uk resuscitation council [ ] . this is in line with the european resuscitation council guideline [ ] . the aim of this audit was to review compliancy to this guideline at the intensive care unit at the bristol royal infirmary . a retrospective audit was performed over a six-month period in adults who were admitted to the intensive care unit at the bri following an oohca whom later died during that admission ( patients). the focus was on whether the neuroprognostication and end-of-life (eol) care received was as per the standards set by the uk resuscitation council. the main neuroloical examinations documented were pupillary reflex ( %), corneal reflex ( %) and motor response to pain ( %). . % of patients received an ssep analysis > hours post-rosc, . % underwent an eeg and . % had > serum neuron-specific enolase measurements recorded. all patients ( %) underwent a ct head during their admission. . % of patients were referred to palliative care during their admission. % of patients were prescribed all eol medications. most common prescriptions included alfentanil ( . %) and midazolam ( . %). finally, % of appropriate patients were referred to be potential organ donors. the audit reflected our local practice and that some parameters were not being maintained as set by uk resuscitation guideline. multiple introduction: the prognostication of neurological outcome in comatose out-ofhospital cardiac arrest (ohca) patients is an integral part of post cardiac arrest care. biochemical biomarkers released from cerebral cells after hypoxic-ischemic injury represent potential tools to increase accuracy in predicting outcome after ohca. currently, only neuronspecific enolase (nse) is recommended in european prognostication guidelines. in this study, we present the release dynamics of gfap and uch-l after ohca and evaluate their prognostic performance for long-term neurological outcome in ohca patients. serum gfap and uch-l were collected at , and h after ohca. the primary outcome was neurological function at -month follow-up assessed by cerebral performance category scale (cpc), dichotomized into good (cpc - ) and poor (cpc [ ] [ ] [ ] . outcome prognostic performance was investigated with receiver operating characteristics (roc) by calculating the area under the receiver operating curve (auroc) and compared to nse. results: of included patients had at least one serum gfap or uch-l value at , or h after ohca. gfap and uch-l levels were significantly elevated in patients with poor outcome. gfap and uch-l discriminated excellently between good and poor neurological outcome at all time-points (auroc gfap . - . ; uch-l . - . ) and overall predictive performance measured by auroc of gfap and uch-l was superior to nse (auroc . - . ) ( figure ). however, the roc at the highest specificities of uch-l and gfap overlap those of nse and comparing the sensitivities for uch-l and gfap with those of nse for the highest specificities (> %) revealed higher sensitivities for nse than for uch-l and gfap at and h. gfap and uch-l predict poor neurological outcome in patients after ohca excellently and with a higher overall accuracy than nse, but both biomarkers perform inferior to nse at specificities over % at and h limiting their clinical use to guide decisions on prognosis. blood pressure after cardiac arrest and severity of hypoxicischemic encephalopathy c endisch , s preuß , c storm introduction: blood pressure management in post cardiac arrest (ca) patients ensures sufficient cerebral perfusion to avoid secondary brain injury. in local chain-of-survival improvements affect p-ohca survival [ ] [ ] [ ] [ ] [ ] . also initial rhythm in p-ohca is an important predictor of survival [ , ] . little is known about the relationship between initial rhythm in p-ohca and long-term outcome [ ] [ ] [ ] . our aim was to establish the relation between shockable rhythm and favorable long-term outcome in pohca. all children aged day- years who experienced non-traumatic ohca between - and were admitted to the sophia children's hospital in rotterdam were included. long-term outcome was determined using a pediatric cerebral performance category score at the longest available follow-up interval. the primary outcome measure was survival with favorable neurologic outcome, defined as pcpc - or no difference between pre-and postarrest pcpc. the association between shockable rhythm and the primary outcome measure was calculated in a multivariable regression model, adjusted for the pre-defined variables. from the patients included in the year study period ( %) patients survived to hospital discharge of which patients ( %) had favorable neurologic outcome (median follow-up duration of months). the rate of favorable neurologic outcome rose from % in to % in (p < . for trend) (fig. ) the odds of favorable neurologic outcome at the longest follow-up duration were significantly higher after a shockable initial and unknown rhythm. secondly, trend analysis showed an increase in aed defibrillation and shorter cpr duration. this was followed, finally, by a rise in rosc, survival to hospital discharge and favorable neurologic outcome rate. low socioeconomic status is associated with worse outcome after cardiac arrest. this study aims to investigate if patients´socioeconomic status impacts the chance to receive early coronary angiography after cardiac arrest. in this nationwide retrospective cohort study, patients admitted alive after out-of-hospital cardiac arrest (ohca) and registered in the swedish registry for cardiopulmonary resuscitation were included. individual data on income and educational level, prehospital parameters, coronary angiography results and comorbidity were linked from other national registers. in the unadjusted model there was a strong correlation between income level and rate of early coronary angiography where % of patients in the highest income quartile received early angiography compared to % in the lowest income quartile. when adjusting for confounders (educational level, sex, age, comorbidity and hospital type) there were still higher chance of receiving early coronary angiography with increasing income, or . (ci . - . ) and . (ci . - . ) for the two highest income quartiles respectively compared to the lowest income quartile. when adding potential mediators to the model (initial rhythm, location, response time, bystander cardiopulmonary resuscitation and if the arrest was witnessed) no difference in early angiography related to income level where found. the main mediator was initial rhythm (figure ). higher income is strongly related to the rate of early coronary angiography after ohca. this finding is consistent when adjusting for known confounders. however, the association between income and early angiography seems to be mediated by initial rhythm. patients with low income more often presents with non-shockable rhythms which lowers the likelihood to undergo early coronary angiography. a. the total amount of mortality as a stacked bar: in light-red the number of patients who deceased at scene, in green the number of patients deceased during admission, in red patients who died after discharge. the grey line is the total number of inclusions. b. the rate of bystander aed use, rate of initial shockable rhythm, rate of less than minutes of cpr and rate of favorable neurologic outcome over time. p for trend significant for bystander aed use, less than minutes of cpr and favorable neurologic outcome. trend analysis performed using binary logistic regression for dichotomous data (and a kruskal-wallis test for non-normally distributed continuous data) effect of simulation teaching of cardiopulmonary resuscitation for nursing v spatenkova introduction: simulation teaching is a modern type of critical care (cc) education. the aim of this study was to assess the effect of simulation teaching of cc on a comparison of final examination in different model levels of cardiopulmonary resuscitation (cpr) after the first (cc ) and third, final cc . the success rate of cpr was tested in prospective study ( ) ( ) on two groups with a total of students in cc and cc at the faculty of health studies. three semester of undergraduate nursing simulation education (lectures and training) used the laerdal simman g. quality of cpr was evaluated according to parameters: compression depth, compression rate, chest release and time of correct frequency. we tested if cpr quality differed between the two groups. for the compression depth and compression rate parameters, first the conformity of variance was verified and then two-sample t-test. as the chest release and time of correct frequency are recorded as percentages, the wilcoxon rank-sum test was conducted for these parameters. to ensure good resuscitation, all recorded parameters must be properly performed during resuscitation. thus, pivot tables were used to generate statistics and test if the number of correctly performed resuscitation parameters for cc and cc differ. the compression depth parameter was statistically significantly higher for the cc than for the cc (p= . ). there were no differences in compression rate (p= . ), chest release (p= . ) and time of correct frequency (p= . ). it was also tested how many of the parameters were performed correctly by students at cpr. the chi-square test shows the relative frequency of cpr success is higher for the cc group than for the cc group. at least out of parameters were correctly performed by % of cc students compared to % of cc students. the study showed a significant improvement of cpr in the final cc and supported the three semester simulation education. changes in blood gases during intraoperative cardiac arrest jj wang, r borgstedt, s rehberg, g jansen protestant hospital of the bethel foundation, anaesthesiology, intensive care and emergency medicine, transfusion medicine and pain therapy, bielefeld, germany critical care , (suppl ):p introduction: blood gas analysis (bga) is a common approach for monitoring the homeostasis during surgery. while it is well known that cardiac arrest (ca) leads to circulatory collapse and disturbances in homeostasis, little is known about changes of blood gas during peri-operative ca. we retrospectively analysed patients ≥ years who suffered from peri-operative ca during non-cardiac surgery from / to / . peri-operative ca was defined as need for cardiac compression during anaesthesia care. collected data included ph, paco , pao , return of spontaneous circulation (rosc) and -day mortality after ca. within the study period, we observed peri-operative ca (m= , f= ; age ± ) during anaesthesia procedures (rosc occurred in patients ( %). days after ca, the mortality was % (n= ), % (n= ) were discharged, and % (n= ) still in hospital. % (n= ) of ca patients had an invasive blood pressure monitoring, % (n= ) had bga before and % (n= ) during peri-operative ca. prior to ca, the average values were: ph . ± . , paco ± and pao ± . during ca, the average values were ph . ± . , paco ± and pao ± . table shows the distributions of blood gas before and during ca. there were no statistical differences between the groups (ph: p= . ; paco : p= . ; pao : p= . ). hypercapnia and respiratory acidosis is common in peri-operative ca. these data suggests inadequate ventilation during peri-operative resuscitation. further studies should focus on its impact on the outcome. ]. comparing cases with and without rosc, there were significant more diagnostics done in the group without rosc but more therapeutic consequences seen in the rosc-group (table ) . icu-ca is frequent. diagnostics to detect reversible causes of ca were used rarely in icu-ca ( %), even in patients without rosc. notably, diagnostics often had therapeutic consequences particularly in rosc. further studies are required to define standardized diagnostic algorithms during icu-ca. continuous monitoring of cardiac patients on general ward were improved short term survival of in-hospital cardiac arrest uj go introduction: the importance of early detection in the in-hospital cardiac arrest (ihca) is emphasized. previous studies have reported that clinical outcomes are improved if ihca is witnessed, or if a patient admitted to a monitored location [ , ] . this study aimed to evaluate the association between continuous monitoring and survival of ihca on general ward. a retrospective cohort study of ihca in patients admitted to ward at an academic tertiary care hospital between january and december was performed. the primary outcome was return of spontaneous circulation (rosc). the secondary outcomes were hour survival and survival to hospital discharge. (table ) . cardiac patients with continuous monitoring on general ward showed improving rosc and -hour survival but not survival to hospital discharge in ihca. in-hospital cardiac arrest is associated with poor outcomes. although steroids are frequently used in patients with septic shock, it is unclear whether they are beneficial during cardiac arrest and after return of spontaneous circulation (rosc). of cardiac arrest patients evaluated, were enrolled. advanced life support was conducted according to the resuscitation guidelines. forty-six patients were randomly assigned to receive methylprednisolone mg during resuscitation, and to receive saline (placebo). after resuscitation, steroid-treated patients received hydrocortisone mg daily for up to days, followed by tapering . there was no significant difference between the two groups in scvo andall the secondary outcomes (p> . for all comparisons). the present study found no significant physiologic benefit of corticosteroid administration during and after resuscitation in hospitalized patients with cardiac arrest. the experiences of ems providers taking part in a large randomized trial of airway management during out of hospital cardiac arrest, and the impact on their views and practice. results of a survey and telephone interviews m thomas introduction: the aim is to explore ems experiences of participating in a large trial of airway management during out-of-hospital cardiac arrest (air-ways- ), specifically to explore: . any changes in views and practice as a result of trial participation. . experiences of trial training. . experiences of enrolling critically unwell patients without consent. . barriers and facilitators for out-of-hospital trial participation. an online questionnaire was distributed to ems providers who participated in the trial. in-depth telephone interviews explored the responses to the online questionnaire. quantitative data were collated and presented using simple descriptive statistics. qualitative data collected during the online survey were analysed using content analysis. an interpretive phenomenological analysis approach was used for analysis of qualitative interview data results: responses to the online questionnaire were received from % of airways- study paramedics and study paramedics were interviewed. paramedics described barriers and facilitators to trial participation and changes in their views and practice. the results are presented in five distinct themes: research process; changes in views and practice regardingairway management; engagement with research; professional identity; professional competence. conclusions: participation in the airways- trial was enjoyable and ems providers valued the training and study support. there was enhanced confidence in airway management as a result of taking part in the trial. study paramedics expressed preference for the method of airway management to which they had been randomized. there was support for the stepwise approach to airway management, but also concern regarding the potential to lose tracheal intubation from 'standard' paramedic practice. causes of medical care-associated cardiac arrest on the intensive care unit s entz introduction: cardiac arrest on intensive care unit (icuca) following therapeutic interventions is of imminent importance, because the interventions are comparatively predictable and precautions can potentially be taken. this study investigates medical care associated complications that led to icuca. intensive care database was screened for patients ≥ years who experienced icuca in a tertiary hospital with five icu (two medical, two surgical, one interdisciplinary, with a sum of icu beds) in germany from - . icuca was defined as receiving chest compression and/or defibrillation after admission on icu and classified as "medical care associated" if it was preceded by a therapeutic intervention (i.e. induced by medication, bedding procedures, iatrogenic injuries, procedure associated). subgroups included patients with recurrence of spontaneous circulation (rosc) vs. no-rosc and patients with vs. without vasopressor therapy before intervention. there were icuca in patients of totally , icu patients. medical care associated complications leading to icuca were detected in cases ( %) [incidence . / , (ci . - . )]. icuca following therapeutic interventions occurred because of circulatory insufficiency [n= ( %)], respiratory failure [n= ( %)] and airway associated problems [n= ( %)]. nine of the patients ( %) with care-associated icuca died. table demonstrates therapeutic interventions followed by icuca. care-associated complications were common reasons for icuca. most of events were induced by circulatory insufficiency due to induction of anaesthesia and bedding procedures. further investigations should focus on preventive strategies, such as vasopressor infusion before therapeutic interventions. in-hospital cardiac arrest (ihca) is a lethal event. however, ihca has received less attention than out-of-hospital cardiac arrest (ohca). there have been some studies on ihca; however, there is a lack of information on the evidence and clinical features of ihca compared with information for ohca. we therefore conducted this study to clarify important aspects of the epidemiology and prognosis of ihca in patients with code blue activation. we carried out a retrospective observational study of patients with code blue events in our hospital during the period from january to october . we obtained information on the characteristics of patients including age and gender, ihca characteristics including the time of cardiac arrest, event being witnessed, presence of bystander cardiopulmonary resuscitation (cpr), initial shockable rhythm, vital signs h or h before cardiac arrest, survival to hospital discharge (shd), and the cardiac arrest survival postresuscitation in-hospital (caspri) score. the primary endpoint was shd. we performed univariate and multivariate logistic regression analyses. a total of code blue events were activated during the study period. finally, patients were included in this study. overall, the shd rate was . %. the median time of cpr was min (interquartile range, - min). the rate of initial shockable rhythm was . %. there were significant differences in cpr duration, shockable rhythm, and caspri score between the shd group and non-shd group by univariate-logistic regression analysis. caspri score was found to be the most effective predictive factor for shd (or= . , p= . ) by multivariate-logistic regression analysis. our results demonstrated that caspri score is associated with shd in cpa patients with in-hospital code blue events. caspri score in ihca patients would be a simple and useful adjunctive tool for management of post-cardiac arrest syndrome (pcas). peri-operative cardiac arrest in prematurityincidence and causes at a tertiary care hospital between - g jansen, j popp, e lang, r borgstedt, b schmidt, s rehberg protestand hospital of the bethel foundation, anaesthesiology, intensive care and emergency medicine, bielefeld, germany critical care , (suppl ):p the peri-operative care of premature pediatric patients requires special expertise and is therefore reserved for specialized centers. although premature birth is described as a risk factor for peri-operative complications and cardiac arrest (poca) there are no data on its incidence and causality in this particular population [ ] . the present study investigates the incidence and causality of pediatric poca at a tertiary care hospital and level i perinatal center in germany. in the anesthesia database of the study center, all anaesthesiological procedures in patients < years of age were examined for poca in preterm infants (gestational age < th week of gestational age) between and . the peri-operative period was defined between the beginning of anesthesiological care up to minutes after anesthesia and/or sedation. we defined cardiac arrest as the necessity of chest compressions. the perioperative phase and the cause of the poca, gestational age and birth weight were recorded. between and , ( . %) of the , pediatric anesthesiological procedures were performed on premature infants. in total, poca occurred in of these patients (f= , m= ; average gestional age ± days; average birth weight ± g (incidence . %, ci . - . %). the time of occurrence and the causes of poca are shown in table . poca in premature babies is rare and has an incidence of . %, which is significantly higher than the non-premature babies. the main causes are problems or complications associated with the respiratory tract and its management, as well as massive hemorrhage. introduction: peri-operative cardiac arrest (poca) in children's anesthesia care is a dreaded event. depending on the country and population, studies describe incidences between . - . per , children's anesthetics. there are no data on the current incidence of pediatric poca in germany. the present study investigates the incidence of poca at a tertiary hospital and level i perinatal center in germany. in the anesthesia database of the study center, all anaesthesiological procedures in patients < years were examined for poca. the peri-operative period was defined between the beginning of anesthesia care up to minutes after anesthesia or sedation. cardiac arrest was defined as the necessity of chest compressions. age, weight, asa status, cause of death and survival after days were recorded. results: poca (median weight was g [q ;q ( )]) were observed in , anaesthesiological procedures (incidence . ± . per , [ci . - . ]). table shows the distribution of the individual age groups, incidences and mortalities of poca. peri-operative -day mortality was per , [ci [ ] [ ] [ ] [ ] [ ] . three children died intraoperatively as a result of hemorrhagic shock, one on the picu as a result of malignant hyperthermia. days after poca, more children had died on the icu due to their underlying disease. poca is a rare event. risk factors are an age < days and an asa status ≥ iii. the main cause of peri-operative death in patients < years of age is massive hemorrhage, the -day mortality is determined by the underlying disease. in-hospital cardiac arrest -predicting adverse outcomes t partington, j borkowski, j gross northwick park hospital, anaesthesia/critical care, london, united kingdom critical care , (suppl ):p introduction: cardiac arrest occurs in . per hospital admissions in the uk. return of spontaneous circulation (rosc) is achieved in approximately half of resuscitation attempts, but rate of survival to hospital discharge is substantially lower [ ] . in our centre, post-arrest care accounts for . % of icu admissions. premorbid social function is purported to affect outcomes, but comorbidity scores are more often used for risk stratification. using a novel social function score alongside an existing comorbidity scale, we aimed to identify trends to inform management of patients at risk of deterioration. a six-month prospective observational study was conducted in a major uk hospital from october to april . for all adult inpatient cardiac arrests, medical notes were reviewed and data collected on the following domains: patient demographics comorbidities and functional status admission details post-arrest events statistical analysis was performed using student's unpaired t-test. results: cardiac arrests occurred. % were in medical patients, with the majority male ( %) and aged over ( %). % were emergency admissions, with mean duration of hospital stay pre-arrest days. in cases ( %) sustained rosc was achieved. however, seven of these ( %) were not subsequently admitted to the icu. only six patients ( %) survived to hospital discharge. pre-admission function and comorbidity were worse in patients who did not survive to discharge ( fig. ), but these were not statistically significant in view of small survivor group size. in an increasingly frail inpatient population, a substantial proportion of patients in whom circulation is restored after cardiac arrest are subsequently considered unsuitable for icu admission. given our understanding of inferior outcomes in patients with poor physiological reserve, we encourage early discussion regarding the appropriateness of cpr in selected patients, guided by social function and comorbidity. references: . national cardiac arrest audit / introduction: there are studies that determine events related to poor outcome in cardiac arrest [ ] . in our study, following parametres were determined ohca patients; age median years, asian/europe/syrian, bystander cpr, bystander aed, ems defibrillation, initial cardiac rhythm, prehospital rosc, corneal and pupillary light reflex and day survival. we determineted poor prognostic sign with post-cardiac arrest patients. in this study, we identified the causes of poor outcome in patients with ohca. this was a single-centre, retrospective study. we determined incidence and epidemiological factors including: demographics, initial cardiac rhythm. our study population were non-traumatic ohca. our icu, all ohca patient were evaluated wtih echo, and fluid, inotrope and vazopressor were added according to cardiac performance. results: during our study, patients who were admitted to intensive care unit between - were screened. of these patients were out-of-hospital arrest and of them were in-hospital arrest. development of cerebral oedema during treatment in hospital remains a poor prognostic sign. the evaluation of initial cardiac ritm is useful to predict neurological outcome in post-cardiac arrest patients. survival after ohca remains low. the evaluation of initial cardiac ritm is useful to predict mortality and neurological outcome in postcardiac arrest patients. basic life support (bls) education and training for school children is active in japan. however, the bls action by schoolchildren may be limited by school rules. this study aimed to analyse the time factors for basic life support performance and outcome in classmatewitnessed out-of-hospital cardiac arrest (ohca) and to investigate how schoolchildren act when they detect ohca. methods: nation-wide database for , school children cases with ohca and local extended database for , ems-unwitnessed ohca, both of which were prospectively collected during the period of - , were retrospectively analysed. proportion of schoolchildren-detected ohca was low in classmate cases ( . %, / ) in nationwide database and extremely low in all ems-unwitnessed ohcas ( . %, / , ) in local database. nationwide database analyses revealed that both emergency call and bystander cpr were delayed when a classmate witnessed the ohca case: median, vs. min and vs. min, respectively. classmate-witnessed cases were associated with higher incidences of shockable initial rhythm, aed use and traumatic causes. the rate of neurologically favourable outcome was . % and . %, respectively in classmate-witnessed and other cases: adjusted or; % ci, . ; . - . . of cases detected by schoolchildren in our prefecture, ( %) cases had presumed cardiac aertiology and ( . %) cases were caused by suicide attempts (hanging and fall). school children placed emergency calls as the first action only in ( . %) cases. emergency calls were largely delayed when school children dialled other numbers or left the scene to seek adult help. school children were rarely involved in bystander cpr ( %) and aed placement ( %). school children are rarely involved in entire bls. emergency calls and bystander cpr are delayed when schoolchildren act to seek help. because schoolchildren detect suicide-related ohcas, psychological care to schoolchildren involved in bls may be necessary. prognostic value of neutrophil/lymphocyte and platelet/ lymphocyte predicting cardiopulmonary resuscitation with spontaneous circulation recovery c li the affiliated suzhou hospital of nanjing medical university, suzhou, china critical care , (suppl ):p to investigate the predictive value of peripheral blood neutrophil-tolymphocyte ratio (nlr) and platelet-to-lymphocyte ratio (plr) on inhospital mortality in patients with spontaneous circulation recovery after cardiac arrest. a retrospective analysis was made of patients who recovered from cardiac arrest in our hospital from april to november and were admitted to the intensive care unit for more than hours. they were divided into survival group and death group according to the outcome of discharge.the dynamic changes and differences of nlr and plr in hours and - hours after admission to icu between the two groups were analyzed and compared. multivariate analysis and roc curve were used to explore the predictive value of nlr and plr for in-patient mortality. compared with the survival group, plr in the dead group was significantly lower within hours of admission to the intensive care department (p < . ), while nlr in - hours was significantly higher (p < . ). the nlr of surviving group was significantly lower than that of hours (p < . ), while the nlr and plr of death group were not significantly different (p < . ) from that of hours (p < . ). multivariate logistic regression analysis and roc curve showed that nlr of - h in icu was an independent risk factor for predicting in-patient mortality, and had high sensitivity and specificity in predicting death outcomes. neutrophil to lymphocyte ratio, platelet to lymphocyte ratio can help to judge the outcome of patients with cardiac arrest and recovery of autonomic circulation after cardiopulmonary resuscitation. [ , ] patients with sofa score > (vs sofa score ≤ ) had a higher free iron level ( . μmol/l vs μmol/l, p = . ) ( figure ). we found a positive correlation between free iron level at h and changes of sofa score between h and h (r= . ic [ . ; . ]). out-of-hospital cardiac arrest is associated with a significant change of plasma free iron level. free iron level at admission is associated with short term outcome. further research is warranted to better determine the significance of such changes. the optimal level of arterial oxygen in the post-resuscitation period is unknown. recent studies show conflicting results in regard to hyperoxia and its association with survival after out-of-hospital cardiac arrest (ohca) [ ] . the aim of this trial is to study the association between early hyperoxia after ohca with return of spontaneous circulation (rosc) and -day survival. observational study using data from three swedish national registers (i.e. intensive care, cardiac arrest and national patient registries after a successful resuscitation, a systemic inflammatory response occurs, and the c-reactive protein (crp) level represents the degree of inflammation [ ] [ ] [ ] . this study examined the association between increased inflammation and early-onset pneumonia (eop) in patients treated with extracorporeal cardiopulmonary resuscitation (ecpr) after out-of-hospital cardiac arrest (ohca). this retrospective study included data of patients with ohca treated with ecpr admitted to st. luke's international hospital between april and april . the exclusion criteria were as follows: age < years, therapeutic hypothermia withdrawal due to death or circulatory failure, or sepsis as a suspected cause of cardiac arrest. patients were diagnosed with eop according to clinical signs and symptoms acquired after a hospitalization period of > h and within days of admission. the crp levels were measured daily from admission to day . we studied patients with a median age of years (interquartile range: - years). furthermore, ( %) patients were males, and the median time interval from collapse to adequate flow was ( - ) min. all patients received prophylactic antibiotics, and ( %) of them had favorable neurological outcomes (cpc, - ). eop occurred in ( %) patients, with a significantly higher crp level on day than that in those without eop ( . categorizing reasons for death after ecpr is important for comparing outcomes to other studies, assessing benefits of interventions, and better define this heterogeneous patient collective. a categorizing for death after cardiac arrest in both in-hospital (ihca) and outof-hospital (ohca) arrests has been proposed in non-ecpr patients by witten et al. here, we adopt this categorization to ecpr patients. single-center, retrospective, cohort study of patients without rosc after ihca or ohca and ecpr between and . patients with survival below hours were excluded. patients were allocated to one of five predefined reasons for death. results: va-ecmo patients were included (age . ± . , . % female, % ecpr, day survival . %). reasons for death for patients with va-ecmo for shock (survival %) and ecpr ( %) were: neurological withdrawal of care ( % vs %), comorbid withdrawal of care ( % vs %), refractory hemodynamic shock ( % vs %), respiratory failure ( % vs %), and withdrawal due to presumed patient will ( % vs %) ( figure ). the differences in reasons for death among the two groups were significant (p < . ), driven by withdrawal due to neuroprognostication, comorbidity and hemodynamic instability. categorizing death after va-ecmo into five categories is feasible. there are significant difference between patients with va-ecmo for shock and ecpr. interestingly, only a quarter of patients after ecpr died due to brain damage. introduction: scarcity of potential dead brain donors and the persistent mismatch between supply and demand of organs for transplantation has led the transplant community to reconsider donation after circulatory death (dcd) as a strategy to increase the donor pool. normothermic regional perfusion (nrp) by extracorporeal membrane oxygenation (ecmo) may be the most effective method for preserving abdominal organs in dcd, especially in liver transplantation [ , ] . a pitfall of this method is its complexity and the unavailability of this resource in some hospitals, especially in regional hospitals, where potential dcd donors may exist. aim of this study is to report the use of mobile ecmo team in controlled dcd. from june to november our group has worked as a mobile ecmo team for cdcd outside our center. portable equipment included cannulation material and the ecmo device. the transplant team consisted of transplant coordinator (anesthesiologist-intensivist, ecmo operator and organ extraction supervisor), cardiac surgeon (cannulation), interventional radiologist (cannulation) and one cardiovascular perfusionist (ecmo operator). twenty-five cdcd donations were performed. characteristics of donors and organs retrieved are summarized in figure . from cdcd, livers, lungs, kidneys were obtained. the evolution of grafts and receptors was favorable at day post-transplant. mobile ecmo teams may enable cdcd in hospitals without these resources, thereby increasing the pool of donors and optimizing graft outcomes. what is the useful coagulation and fibrinolysis marker for predicting extracorporeal membrane oxygenation circuit exchange due to intra-circuit thrombus? y izutani, k hoshino, s morimoto, k muranishi, j maruyama, y irie, y kawano, h ishikura fukuoka university hospital, emergency and critical care center, fukuoka-shi, japan critical care , (suppl ):p a thrombus formation is one of the most frequent and adverse complications during extracorporeal membrane oxygenation (ecmo) support. previous studies have reported that increased d-dimer is a useful predictor of thrombus formation within the ecmo circuit. the purpose of this study was to identify coagulation/fibrinolysis markers for predicting the replacement of ecmo circuit due to intra-circuit thrombus during ecmo support. fourteen patients who underwent veno-venous ecmo for acute respiratory failure between january and december were enrolled. these patients received a total of days of ecmo support. of these, days (times) on which the ecmo circuits were replaced was regarded as the replacement group, while the remaining days were considered as the non-replacement group. the several coagulation/fibrinolysis markers were routinely measured every day during ecmo support. we compared with the levels of these markers between two group to identify the most relevant marker for ecmo circuit replacement due to thrombus. the mean duration of ecmo support was ± days, and the mean number of ecmo circuit replacement was . ± . times per patient. ddimer, thrombin-antithrombin complex (tat), plasmin-α plasmin inhibitor complex (pic), and soluble fibrin (sf) were significantly higher in the replacement group rather than in the non-replacement group (p < . , respectively). according to a multivariate analysis, sf was the only independent predictor of ecmo circuit replacement due to thrombus. the odds ratio ( % confidence intervals) for sf ( μg/ml) was . ( . - . ). the area under the curve and optimal cut-off value were . and ng/ml for sf, respectively (sensitivity, %; specificity, %). from these results, we concluded that sf may be the useful marker rather than d-dimer for predicting the replacement of ecmo circuit due to intra-circuit thrombosis. inhomogeneity of lung elastance in patients who underwent venovenous extra corporeal membrane oxygenation (v-v ecmo)-a computed tomography scan study rd di mussi , ri iannuzziello , fm murgolo , fd de carlo , e caricola , na barrett , lc camporota , sg grasso università degli studi di bari "aldo moro", department of emergencies and organ transplant, bari, italy; università degli studi di bari "aldo moro", bari, italy; department of adult critical care, guy´s and st thomas´nhs foundation trust, king´s health partners, london, uk critical care , (suppl ):p in patients with acute respiratory distress syndrome (ards), nonaerated, poorly aerated, and normally aerated regions coexist to variable degrees in lung parenchyma. the recruitment maneuvers aim to reopen collapsed lung tissue. in a theoretical point view, this strategy may also prevent the normal aerated lung tissue hyperinflation [ ] . the objective of our study was to evaluate lung characteristics in terms of hounsfield units (hu), volume and elastance before and after a recruitment maneuver. in patients with severe ards who underwent v-v ecmo, computed tomography scans (ct-scans) at cmh o of continuous positive airway pressure (cpap) and cmh o were performed. the same ct image was selected at the two different levels of pressure. the distribution of lung opacities, in terms of hu, was classified using the "ucla" colour coding table (osirix image processing software, geneva, switzerland). correspondent lung regions of about voxels were selected. the quantitative analysis, in terms of volume air (vair) was performed with maluna software (version . ; maluna, goettingen, germany). elastance was calculated as the pressure(cmh o)/ vair (ml) ratio. results: see figure . lung inhomogeneity occurs also after recruiting maneuvers. our data confirm that the elastance of recruited lung regions is higher than the elastance of the normal aerated lung regions at low positive end-expiratory pressure (peep) (baby lung). on the contrary the "baby lung" frequently develops hyperinflation. the unpredictable pattern of distribution of volume after recruitment maneuverers may explain the controversial role of peep during the ards treatment. . formal recommendations on target, timing, and rate of at supplementation are lacking. we conceived this study to evaluate the effect of prolonged at supplementation in adult patients requiring veno-venous ecmo for respiratory failure on heparin dose, adequacy of anticoagulation and safety methods: before ecmo start patients were randomized to either receive at supplementation to maintain a functional at level between and % (at supplementation group) or not (control group) for the entire ecmo course. anticoagulation was provided with unfractionated heparin following a standardized protocol [ ] . the primary outcome was the dose of heparin required to maintain the ratio of activated partial thromboplastin time between . and . secondary outcomes were the adequacy of anticoagulation measured with anti-factor xa and the incidence of hemorrhagic and thrombotic complications and amount of blood products fig. b) . conclusions: this retrospective analysis was not able to show a survival benefit for additive pp to ecmo support in general. early initiation of pp could be an important factor for improving survival in this setting and should be considered in a randomized controlled trial for further evaluation. cause-specific mortality during extracorporeal membrane oxygenation, a single center review of medical records m panigada, d tubiolo, p properzi, g grasselli, a pesenti fondazione irccs ca´granda ospedale maggiore policlinico, intensive care unit, milano, italy critical care , (suppl ):p introduction: mortality during extracorporeal membrane oxygenation (ecmo) settles around % and the occurrence of bleeding during ecmo is associated with a high mortality rate. however, cause-specific mortality is rarely reported, probably due to the difficulty of its classification. the purpose of the study was to evaluate the agreement between two expert icu physician in the classification of the cause of death of patients supported with ecmo for either respiratory or cardiac support. methods: two intensive care unit (icu) expert staff physicians independently reviewed the entire medical records of all ecmo patients who died before icu discharge from january to september at fondazione irccs ca' granda, milan. they were asked to choose the cause of patient's death among six categories. in case of disagreement, a third expert adjudicated the case. the two reviewers were also asked whether, in their opinion, bleeding during the last hours contributed to death. elso definition of major bleeding [ ] during the last hours was also recorded for each patient. results: two-hundred and two patients were supported with ecmo of whom ( . %) died. most of these patients (n= , . %) died during ecmo. interrater agreement for cause-specific mortality between the two expert physicians was substantial (k . , se . , p< . ) of the discordant cases were categorized as refractory respiratory failure and as multiorgan failure and septic shock respectively. the distribution of cause-specific mortality is shown in figure . major bleeding (elso) was present in ( . %) patients, only in ( . %) of them bleeding contributed to death according to the reviewers. patients treated with early pp while ecmo showed a superior survival to patients treated with late pp or without pp while ecmo. optimal cut off value for duration of ecmo initiation to first pp was calculated using roc-analysis (auc = . ) and the youden-index. highest sensitivity and specificity for beneficial survival were achieved for a beginning of pp in < . days. (log rank= . ). pp: prone positioning p non-invasive mechanical ventilation in veno-venous extracorporeal membrane oxygenation j rilinger, v zotzmann, x bemtgen, pm biever, d duerschmied, c bode, dl staudacher, t wengenmayer heart center freiburg university, department of cardiology and angiology i, freiburg, germany critical care , (suppl ):p introduction: veno-venous extracorporeal membrane oxygenation (ecmo) support can be combined with a variety of different non-invasive ways to deliver oxygen to the patient's lung. several positive effects might be linked to this so called "awake ecmo". so far there is little evidence about indications and outcome of this approach. we report retrospective registry data on all ards patients treated with ecmo support at a university hospital between / and / . in a systematic review of medical records, we distinguished between patients with invasive mechanical ventilation (imv) from the initiation of ecmo therapy (imv group) and patients that received any kind of non-invasive oxygen supply (non-imv group). a total of patients could be analysed. ( . %) patients received non-imv ecmo support. patients receiving non-imv ecmo therapy showed severe underlying pulmonary disease and immunosuppression (fig. ) . these patients had higher rates of lung fibrosis, long-term oxygen therapy, pulmonary hypertension, renal insufficiency and immunosuppression (p< . ). of patients ( %) required imv during the hospital stay in average . ± . [ . - . ] days after ecmo initiation. reasons were hypoxia despite of ecmo, insufficient ecmo-flow, insufficient protective reflexes or patient agitation. patients with initially non-imv ecmo support showed a numerical but not significant lower icu and hospital survival ( . % vs. . %, p= . ). non-imv ecmo support was applied in patients with severe underlying pulmonary disease and/or immunosuppression. in a high proportion of patients the ventilation regime had to be switched from non-invasive to invasive. survival in this very selected cohort was low. in this retrospective analysis no evident benefit for a noninvasive ventilation strategy could be found. the high proportion of patients who switched from non-imv to imv therapy underlines the need for rigorous patient selection. intra-hospital transportation on extracorporeal membrane oxygenation (ecmo) -a single centre experience in ireland. z siddique, s o´brien, e carton, i conrick-martin mater misericordiae university hospital, department of critical care medicine, dublin, ireland critical care , (suppl ):p the objective of this study is to evaluate intra-hospital transportation of patients on extracorporeal membrane oxygenation (ecmo). it is a retrospective analysis of prospectively collected database, performed as part of ongoing quality improvement initiatives. the setting of this study is an -bed, combined surgical and medical adult intensive care unit (icu) located in a -bed hospital that serves as the national referral centre for cardiothoracic surgery, heart & lung transplantation and ecmo in ireland. we reviewed months of data (from to ) regarding patients admitted to our critical care unit who required intra-hospital transfer for diagnostic and/or therapeutic interventions. we also compared the data to available local guidelines. results: patients were transported on ecmo on a total of occasions; the most common indication being ct brain (table ) . ecmo cannulation sites were peripheral in patients, patients were centrally cannulated. median time from start of the transfer until the patient was returned to icu was minutes (range: - ). the ecmo console was placed on a dedicated ecmo trolley apart from two occasions where it was placed on the patient's bed. number of staff required for transport was between to ; with an icu consultant as team leader. ecmo specialist nurses were always present on the transport team. transfers were during normal working hours with happening on a weekend. a total of complications occurred during the transports, of underlying pulmonary disease or status of immunosuppression in ecmo patients without invasive mechanical ventilation which was significant and were not. the significant complication encountered was ventricular tachycardia in a v-a ecmo patient which required electrical defibrillation. no adverse events related to transport were seen following return to icu. in this single-centre study, we have demonstrated safe intra-hospital transport of ecmo patients. the use of local guidelines, appropriate personnel and performance during normal working hours is recommended. a novel approach for flow simulation in ecmo rotary blood pumps a supady , c benk , j cornelis , c bode , d duerschmied heart center freiburg university, cardiology and angiogiology i, freiburg, germany; heart center freiburg university, department of cardiovascular surgery, freiburg, germany; fifty technology gmbh, freiburg, germany critical care , (suppl ):p introduction: extracorporeal membrane oxygenation (ecmo) is used increasingly in critically ill patients suffering from acute respiratory failure, cardiogenic shock or cardiac arrest. however, this therapy can have deleterious side effects such as bleeding or clotting complications and hemolysis. these complications are particularly caused by physical stress acting upon the blood components while passing through the ecmo system, especially within the rotary pump. we here present a novel approach to simulate blood flows through rotary blood pumps used in current ecmo systems in order to better understand the genesis of these complications. geometries of the xenios dp (xenios ag, heilbronn, germany) rotary pump were reconstructed by ct-scans and manual measurements using computer-aided design (cad). the computational fluid dynamics (cfd) simulation was performed using the software preon-lab (fifty technology gmbh, freiburg, germany), which implements a mesh-free lagrangian method requiring minimal preprocessing of the cad data. the geometries are introduced to the simulation model as tessellated surfaces. five operating points have been specified by the rotation of the centrifugal fan and the corresponding inflow and outflow of blood. the blood is approximatively modelled as a newtonian fluid with a density of kg/m . preonlab allows detailed assessment of the blood flow while passing through the rotary pump including analysis of local flow rates, pressure gradients and shear stress acting upon the blood. dead zones in the fluid flow can be detected which gives reference points for optimizations of the pump design. for the first time, we demonstrate a novel approach for flow simulation in an ecmo rotary pump ( figure ). this approach may help better understand hemodynamics within the extracorporeal system to define optimal operating points or re-design components aiming to limit hemolysis, coagulation disorders and bleeding in seriously ill patients. one-year experience of bedside percutaneous va-ecmo decannulation in a territory ecmo center in hong kong km fong, sy au, pw leung, kc shek, hj yuen, sk yung, hl wu, so so, wy ng, kh leung queen elizabeth hospital, intensive care unit, hong kong critical care , (suppl ):p when veno-arterial extra-corporeal membrane oxygenation (va-ecmo) support can be terminated, arteriotomy wounds of the patients of are traditionally closed by open repair in the operation theaters. lots of manpower are involved and timeslots in operating theaters are scarce. transport of the critically-ill is risky. successful va-ecmo decannulation using percutaneous device called proglide has been reported and our group had adopted and modified this approach [ ] . methods: this is a retrospective study analyzing the one-year experience of bedside va-ecmo decannulation. our institution is a -bed tertiary ecmo referral center in hong kong. our first bedside decannulation was performed in november , and since then, this practice had replaced the traditional open repair, unless contraindicated. data from november to october were analyzed. in the study period, patients received va-ecmo. survived to decannulation and received bedside percutaneous decannulation. their median age was ( - ). the default arterial catheter size was fr, with fr in cases and fr in one. five ( %) failed percutaneous closure and they were subsequently surgically repaired without extra corporeal life support (ecls) continues to be associated with high mortality rates. our ability to predict outcome prior to initiation ecls remains limited. here we take a single cell rnaseq approach in an effort to identify novel immune cell types that are associated with-and may contribute to-survival on ecls. whole genome transcriptomic profiles were generated from~ , peripheral blood monocytes obtained from patients at the time of cannulation for veno-arterial ecls (va-ecls). within each subpopulation, differential gene expression analysis was performed to identify new markers associated with survival. findings were validated in a additional cohorts by flow cytometry. surviving patients had significantly higher proportions of cd + nkt cells (cd + /cd + /cd -/cd + ) that were cd + (p = . , fdr < . ) ( figure ). to validate this observation, we performed fc analysis of a second cohort of patients. for each patient, we quantified the proportion of cd + nkt cells that were cd + . using the median proportion as the cutoff, we again found that a high proportion of cd + cells among cd + nkt cells was predictive of hour survival (p= . ). we noted that while high levels of cd + cells among the cd + nkt cells was protective in this cohort of va-ecls patients, this relationship did not hold for patients with sepsis. as only a few the va-ecls patients were septic, we analyzed a third cohort of septic ecls patients. we observed that high levels of cd + cells among the cd + nkt populations was not protective in this population. the proportion of cd + nkt cells that are positive for cd is predictive of survival among patients undergoing va-ecls for noninfection related indications. introduction: the use of calcium sensitizers has grown enormously in the last decade, probably due to their interesting pharmacodynamic properties. levosimendan (ls) is frequently administered in patients under mechanical circulatory support. we performed a retrospective evaluation of patients treated with ls prior to weaning from mechanical support. this evaluation was combined with a review of the literature. a query of our icu patient data management system revealed patients receiving ls prior to or during vad/ecls support. outcome data were obtained from the patients medical records. of our patients, % was successfully weaned off ecls. fourteen patients ( %) died before being discharged of whom while on ecls support. of the weaned patients, died afterwards. of the converted patients needed subsequent veno-venous ecls support for right ventricular support after the implantation. survival to discharge ratio for the whole group was %. more detailed demographic results can be found in table . a pubmed search using the terms "(ecmo or ecls) and ls and weaning" resulted in publications which dealt specifically with weaning of ecls support. several weaning approaches are available, however poor outcome has remains a problem. some recent studies show a possible beneficial effect of ls infusion prior to weaning from ecls. however most of these studies are retrospective or observational at best. because ls is primarily reserved for the most severe cases, outcome interpretation is difficult. overall weaning success ranges from %- % and variation is very dependant of inclusion criteria. the calcium sensitizer ls can be used when weaning off patients from ecls, certainly given its low incidence of complications. future, large randomized trials are however needed in order to confirm this strategy. cardiogenic shock is well described in newly diagnosed pheochromocytoma, and crisis may be precipitated by hemorrhage into tumour. v-a ecmo represents a rescue therapy in a subset of these patients refractory to medical management, facilitating cardiac recovery and subsequent definitive surgery. consent to publish: written informed consent for publication was obtained from the patients. during a spontaneous breathing trial respiratory mechanics can worsen, and respiratory muscle effort can increase, leading to respiratory muscle fatigue, pump failure, hypercapnia and an unsuccessful weaning from mechanical ventilation. this case report discusses the possibility of applying extracorporeal co removal (ecco r) to reduce respiratory muscle effort in a liver transplant recipient who already failed three weaning attempts from mechanical ventilation. the ecco r membrane lung was integrated into a conventional renal replacement therapy circuit and blood flow was increased from to ml/min. measurements of respiratory mechanics (including esophageal pressure, as shown in fig. ) were used to assess the reduction of respiratory effort before and during the application of ecco r. was delivered through a fr-double-lumen-cannula; ml/min blood-flow with lt oxygen sweep-gas-flow and aptt . - baseline were maintained (iv-heparin). in all cases respiratory and metabolic parameters improved without complications ( figure ). ecco r-crrt facilitated extubation ( out imv pts). in out of pts at risk of niv failure, it avoided imv. treatment mean duration was ± hours, mean lenght of icu stay was ± days. all patients survived to the treatment, nevertheless patients died due to irreversible multiple mof. in our aecopd series prismalung®-prismaflex® facilitated weaning from imv and avoided intubation in patients at risk of niv failure without complications. these positive results may be related to minimal invasiveness of the low-flow device used and may constitute the rationale for a larger randomized controlled trial. consent: written informed consent for data publication has been obtained. extracorporeal the primary outcome findings from the supernova trial [ ] demonstrated that the use of extracorporeal carbon dioxide reamoval (ecco r) allows a reduction in tidal volume (tv) to ultraprotective levels (≈ ml/kg predicted body weight or pbw) during mechanical ventilation in ards patients without significant increases in the arterial partial pressure of carbon dioxide (paco ). unfortunately, it was not feasible to directly measure ecco r rates during the trial. we used a mathematical model of whole-body oxygen (o ) and carbon dioxide (co ) transport and biochemistry [ ] to calculate ecco r rates that permit a fit to the data reported for hemolung (alung technologies) and ila (novalung)/cardiohelp (getinge) devices in the supernova trial [ ] . the mathematical model was calibrated under baseline conditions where patients were mechanically ventilated at a tv of ml/kg pbw in the absence of an ecco r device; the o consumption rate, co production rate and pulmonary shunt fraction were adjusted to match the measured baseline arterial partial pressure of o and paco . assuming all baseline parameters were fixed, tv was then reduced to . ml/kg pbw and the mathematical model predicted the ecco r rate to the change in the paco level. model predictions for the devices are shown in table . these predictions suggest that ecco r rates for ila/cardiohelp devices were approximately twice those for hemolung devices during the supernova trial. these results may be useful to evaluate the expected performance of novel ecco r devices. efficiency and safety of a system crrt plus ecco r to allow ultraprotective ventilation protocol in patients with acute renal failure f maldarelli despite renal function replacement techniques (crrt), a patient who develops acute renal failure(aki) in intensive care unit (icu) has a mortality rate of - %. this risk is partly due to the adverse effect of aki on other organs than the kidney. respiratory complications are frequently associated with the development of aki. new machines combining crrt with a carbon dioxide removal membrane (ecco r) allows the setting up of an ultra-protective ventilation ( ml/kg of predicted boby weight (pbw)) to reduce any lung damage from mechanical ventilation (mv). the reduction in tidal volume (vt) is associated with a decrease in lung damage partly triggered by aki. we evaluated the efficacy of a combined system crrt+ecco r to reduce the vt to ultraprotective values in patients with acute respiratory failure and aki. ards is a syndrome with high morbidity and mortality. an emerging treatment option is ecco r, but the benefit its remains unclear. we assess different degrees of ecco r and varying dead space (ds) on ventilator settings in order to minimize mechanical power. we calculated mechanical power as ( ) power=rr*{Δ〖vt〗^ *[ / *el+rr*( +i:e)/( *i:e)*r]+ Δvt*peep} (el: system elastance, r: airway resistance, peep: positive end expiratory pressure, i:e: inspiratory to expiratory ratio). we calculated the combination of respiratory rate (rr) and tidal volume (vt) ("optimal rr" and *optimal vt*) leading to minimal applied power for a stable carbon dioxide elimination of ml/min (vco ) for two scenarios: ) variation of physiological ds from to % of vt at a fixed rate of eccor . ) variation of ecco r of either , , or ml/min at a fixed physiological ds of %. the alveolar ventilation (va) necessary to eliminate the vco was calculated as ( ) va= (-vco *σ_co *r*t*( +k_c ))/(vco /q-p_vco *σ_co *r*t*(( +k_c ))/ ) σco : co solubility in blood, r: gas constant, t: temperature. pvco : venous partial pressure, kc: function of ph ( . for a ph of . ), q: blood flow [ l/min]). increasing ds from to % increases the minimal mechanical power from . to . j/min, primarily caused by an increase of optimal vt ( - ml). optimal rr was only slightly increased ( . - . /min, figure panel a). for varying ecco r removal, necessary ventilation ranges from . to . l/min. this predicts a minimal power between . and . j/min with an unchanged optimal vt ( - ml) and an increasing optimal rr ( . to . /min ( figure panel b)). in order to minimize mechanical power, increasing shunt or co production should be met with increases in rr while increases in ds should be met with increases in vt. our results indicate that during ecco r, mechanical power and thus risk for lung injury can be minimized with higher vt compared to conservative ventilation strategies. validity of empirical estimates of physiological dead space in acute respiratory distress syndrome jd dianti, eg goligher, as slutsky university of toronto, interdepartmental division of critical care medicine, toronto, canada critical care , (suppl ):p increased physiological dead space fraction (v d /v t ) is a hallmark of the acute respiratory distress syndrome (ards) and has been shown to predict ards mortality. v d /v t is also important in estimating the reduction in tidal volume (v t ) and driving pressure (Δp) with extracorporeal co removal (ecco r). v d /v t can be measured with volumetric capnography but empirical formulae using the patient's age, weight, height, gender and paco have been proposed to estimate v d /v t based on estimates of co production (v co ). the accuracy of this approach in critically ill patients, however, is not clear. secondary analysis of a previously published trial [ ] in which v d /v t and v co were measured in ards patients. estimated dead space fraction (v d,est /v t ) was calculated using standard formulae. agreement between methods was evaluated by bland-altman analysis. the predicted change in Δp with ecco r was evaluated using both measured and estimated alveolar dead space fraction (v dalv /v t ). results: vd,est/vt was higher than measured vd/vt, with a low correlation between the (r = . ). vco was underestimated by the predicted approach (table ) , accounting for % of the error in estimating vd/vt. the expected reduction in Δp with ecco r using vdalv/ vt was in reasonable agreement with the expected reduction using introduction: acute respiratory distress syndrome (ards) is a common condition in critically ill patient. however neuromuscular blockers (nmb) result controvertial in early treatment of ards [ ] . we ought to search systematically and realize a meta-analysis on the matter. an electronic search of randomized clinical trials in adult patient treated with early neuromuscular blockers compared without neuromuscular blockers in ards. the primary objective of the analysis was the mortality at to days. secondary endpoints included mechanical ventilation free days, icu acquired weakness and barotrauma. the search obtained studies for the analysis [ ] [ ] [ ] [ ] [ ] [ ] (figure ). the early use of neuromuscular blockers in ards showed no increase in mortality, but the results should be taken with caution. there was no differences in mechanical ventilation free days. barotrauma is less with the use of nmb. ultrasound is fairly sensitive in the detection of lung infiltrates in patients with hematologic malignancies. in patients with pneumonia requiring intensive care (icu) admission, we hypothesise that abnormal right ventricular (rv) function is associated with an increased -day mortality. rv dysfunction in critically ill patients has a well-known association with adverse outcomes [ ] . however, its impact on mortality in patients with pneumonia has not been directly studied. patients admitted to the queen elizabeth hospital birmingham icu between april and july with a diagnosis of pneumonia who had a formal cardiologist tte were included. abnormal rv function was defined by either depressed function, dilated size or moderate to severe risk of pulmonary hypertension (phtn). abnormal lv function was defined by an lv ejection fraction £ % or grade ii or more diastolic dysfunction. patients with a clinical suspicion of pulmonary embolism were excluded. the primary outcome was -day mortality. continuous data is presented as median (iqr). categorical data is presented as % and analysed using a chi-squared test. results: patients were admitted to icu with pneumonia, of which ( %) had a tte. patients were % male, had a median age of ( - ) and -day mortality of %. abnormal rv function was present in % (n= ), with % depressed, % dilated and % with moderate to severe risk of phtn. rv dysfunction was associated with an increased -day mortality compared to normal rv patients ( % vs. %, p< . ). lv function was abnormal in % (n= ) and was not associated with a higher -day mortality compared to normal lv patients ( % vs %, p = . ). rv dysfunction was associated with a higher -day mortality than lv dysfunction ( % vs %, p = . ). conclusions: this is one of the first studies to demonstrate that abnormal rv function is associated with an increased mortality in icu patients with pneumonia. interestingly, abnormal lv function was not associated with an increased mortality. rakuno gakuen university, anesthesiology, hokkaido, japan critical care , (suppl ):p we previously reported a simple correction method of estimating pleural pressure (ppl) by using central venous pressure (cvp) and that it can be used to estimate ppl and transpulmonary pressure in pediatric patients with respiratory failure. however, it remains unknown that this method can be applied to patients with various levels of chest wall elastance and/or intravascular volume. the objective of this study is to investigate whether our method is accurate in various conditions of chest wall elastance and intravascular volume. the study was approved by the animal care and use committee of rakuno gakuen university. ten anesthetized and paralyzed pigs ( . ± . kg) were mechanically ventilated and subjected to lung injury by saline lung lavage. each pig was subjected to different intravascular volume and different intraabdominal pressures; in each condition, the accuracy of our method was tested. specifically, airway flow, airway pressure (paw), esophageal pressure (pes), and cvp were recorded in each condition, then changes in pes (Δpes) and Δppl calculated using a corrected Δcvp (cΔcvp-derived Δppl) were compared. cΔcvp-derived Δppl was calculated as κ × Δcvp, where κ was the ratio of the Δpaw to Δcvp during the occlusion test. means and standard deviations of the two variables that reflect Δppl (Δpes and cΔcvp-derived Δppl) in all pigs with all conditions were . ± . and . ± . cmh o. the bland-altman analysis for the agreement between Δpes and Δcvp showed a bias of - . the activity and functionality of the diaphragm are difficult to measure in patients ventilated in intensive care. ultrasound can be a useful tool for monitoring diaphragm muscle activity during different ventilation modes. few data currently exist on diaphragm muscle activity in critically ventilated patients [ ] . our goal is to evaluate the respiratory muscular work of the diaphragm with different settings of the respirator by means of an ultrasound scan. the ultrasound assessments of the diaphragm were performed with a mhz linear probe at the apposition zone. we measured the thickening of the diaphragm with the respiratory acts, through the thickening fraction (thickening fraction, tf), defined as:tf = (tdimax -tdimin / tdi min)% tdimax: diaphragm thickness at the end of inspiration (maximum thickness) tdimin: diaphragm thickness at the end of expiration (minimum thickness). ventilatory support was divided into classes: -spontaneous breathing (sb) or continous positive airway pressure (cpap); -pressure support ventilation (psv) with low pressure support ( - cmh o); -psv with high pressure support (> cmh o); -controlled mechanical ventilation (cmv). a total of assessments were performed in patients. the evaluations were all possible at the right hemidiaphragm, while on the left they were not possible in % of the cases. the median tf (iq range) of the ventilation classes was respectively: % ( - %) in sb / cpap; % ( - %) in low-psv; % ( - %) in high psv; and % ( - %) in cmv. the kruskal-wallis test confirms a significant difference between the groups (p < . ). the ultrasound of the diaphragm can be a valid tool for monitoring respiratory muscle activity during mechanical ventilation. introduction: extubation failure is defined as reintubation after hours of extubation in mechanically ventilated critically ill patients. it is associated with morbidity and mortality. the aim of our study was to assess reintubation rates in a busy district general hospital and evaluate the impact of high flow nasal oxygen therapy (hfno) on reintubation rates. we performed a retrospective observational study looking at patients admitted to our bedded level critical care unit ( patients a year) for a period of years between st november and st october . we included patients over years of age who were mechanically ventilated and length of stay was greater than hours. exclusions were age < years, tracheostomy and patients requiring ventilation for < hours. data was collected from ward watcher, a sicsag database and electronic patient records. our study failed to show any impact of hfno on reducing extubation failure. further work is needed to develop a standardized approach to weaning and to consider routine application of noninvasive ventilation to reduce reintubation rates [ ] . fig. (abstract p ) . the bland-altman analysis for the agreement between Δpes and cΔcvp-derived Δppl in various conditions. low: low intravascular volume, normal: normal intravascular volume, high: high intravascular volume, abd-: without an abdominal compression band, abd+: with an abdominal compression band oral endotracheal intubation is common to critically ill patients in intensive care unit. oral care for an intubated patient is important to maintain the moisture of oral mucosa. also, the securement method of oral endotracheal tube developed from cloth tape to commercial tube holder. training powerpoint and video for microteaching was prepared to train up icu nurses to perform the new practice. demonstration and re-demonstration was arranged to assess skills of every nurse. afterwards, each nurse answered a quiz to evaluate the understanding of oetth and its special techniques in application. questionnaire was designed to collect the feedback from all nurses too. the result showed there was nurses ( %) out of nurses achieved full marks in the post-quiz which demonstrated their full understanding of the use of oral ett holder and its nursing care. about the feedback from nurse, % of nurses claimed that they were confident in using the new oetth in clinical setting after training. % of nurses agreed in time-saving of nursing care routine with the use of an oetth. however, only % of nurses agreed that the oetth is effective in prevention of oral mucosa injuries and another % of nursing staff disagreed on its function in improving the patient's oral care. in conclusion, some of the nurses did not agree the prevention of oral mucosa injuries by the new securement method with oetth while some nurses welcomed the new oetth as more easy and effective in oral care to intubated patients. execution of percutaneous dilatational tracheostomy using the standard laryngeal mask airway for ventilation: a prospective survey study g gagliardi , v gagliardi , c chiani , g laccania , f michielan aulss -veneto, anesthesia and intensive care, adria, italy; aulss -veneto, university of padua, adria, italy; aulss -veneto, anaesthesia and intensive care, adria, italy; aulss -veneto, anaesthesia and intensive care, padua, italy critical care , (suppl ):p we fulfilled a survey study dealing with bronchoscope-guided percutaneous dilatational tracheostomies (pdt), using the classic laryngeal mask airway (lma) for the airway management [ ] . the aim was to verify the safety and the effectiveness of the aforementioned procedure methods: we performed an observational prospective survey study enrolling patients hospitalized in the intensive care unit. before performing the tracheostomy, the endotracheal tube has been replaced by the laryngeal mask airway. arterial blood gases, ventilation pressures and tidal volumes have been monitored, registered and compared. the median peak inspiratory pressure has been detected stable in all patients. furthermore, during the ventilation with the laryngeal mask, the tidal inspiratory and expiratory volume difference observed between before and after the bronchoscope positioning, has shown a statistically significant variation. finally, in all cases etco , spo . , pao , and blood ph values persisted within the normal range. the standard lma provides for a reliable airway management and allows an effective ventilation while performing the pdt. once positioned in the supraglottic zone, the lma does not need to be moved throughout all the pdt performance, avoiding risks of displacement, glottic harm and airway device damage, and permitting an easy handling of the bronchoscope, which gives an appropriated visualization of the trachea and a more efficient aspiration. in consequence to the large internal diameter of the lma tube, ppeak has continued to be stable in all patients, providing for minor resistance and inspiratory work. eventually, no late complications, such as tracheal stenosis and infections, have occurred. tracheostomies are the most common surgical procedure performed on critically ill patients. randomized control trials comparing tracheostomy timing in intensive care patients have been equivocal. in order to perform non-urgent tracheostomy in our icu, consent is required from the patient or a formal guardian appointed ad hoc by the courts. since tracheostomies are practically the only elective surgery performed in the critically ill, icu requested guardianship almost always indicates a clinical decision to perform tracheostomy. as appointing a guardian and arranging a tracheostomy takes about a week, the decision to appoint a guardian offers a unique "intention to treat" opportunity to evaluate outcomes in patients for whom tracheostomy is planned. we performed a retrospective analysis over years on patients for whom guardianship was sought excluding those requiring urgent tracheostomy and those with a do-not-resuscitate order. patients were divided according to outcome (tracheostomy, extubation or death prior to tracheostomy) and compared. guardianship was sought for ventilated patients. a decision to withhold tracheostomy was made for patients, who were excluded, leaving patients for analysis. tracheostomy was performed for / ( %) patients, / ( %) were extubated and / ( %) died while waiting for tracheostomy (from nonairway related reasons). tracheostomy was performed on mean ventilation day ± . comparing extubated patients to those who had tracheostomy (table) shows similar demographics, but significantly lower mortality and hospital length of stay. a significant proportion of patients initially planned for tracheostomy were successfully extubated. despite demographic similarities, mortality in this group was significantly lower than for patients undergoing tracheostomy. for a selected subgroup of possibly difficult to characterize patients, delaying tracheostomy may be beneficial. figure ). ptis were analysed by speciality and by outcome. complications occurred in cases (incidence . %). there were cases of subcutaenous emphysema, pneumothorax (occuring d post procedure) and case each of stoma and suture site infection. there was unplanned cannula change within days of insertion. % of cases had cuff inflated on discharge from icu. handover of care was suboptimal; follow up care plans were documented in % of cases. a supervising consultant was present for all ptis. there was a trend of increased insertion by consultant and increased reliance on theatre, with corresponding decrease in the number inserted by trainees. pti in our training icu appears safe with low incidence of complications and good senior support for tracheostomy insertion. emphasis must continue on training junior intensivists in pti. transition of care beyond icu requires further work where currently there is suboptimal handover of care and safety netting for non-icu colleagues. supplemental oxygen administration is ubiquitous in the critical care environment, yet evidence is mounting for the deleterious effects of hyperoxia [ ] . concerns over the adverse effects from hypoxaemia often exceed those of hyperoxaemia in developing world settings, and inconsistent availability of blood gas monitoring may limit judicious oxygen titration. the aim of this project was to audit oxygen delivery practice and introduce qi measures to avoid excess oxygen delivery in a tertiary icu in lusaka, zambia. a prospective snapshot of ventilatory parameters were recorded for critically ill patients over a -week period, including positive end expiratory pressure (peep), fio , and time-course spo . systematic education was provided through group and one to one tutorials to empower nursing and medical staff to titrate oxygen safely and appropriately. repeat data collection was then performed over weeks. initially / patients ( %) were over-oxygenated, as defined by fio > . and spo consistently > %. / patients with an fio of > . had peep ≤ cm ( %). no patient had a pao recorded in the past hours. education was provided as well as implementation of unit protocols above all patient beds documenting a stepwise approach to titration peep and fio . post intervention fewer patients were over-oxygenated: / ( %) had fio > . and spo consistently > %, and / with an fio > . ( %) had a peep ≤ cm. in addition, / ( . %) had a pao recorded within hours. this qi project has shown that nurse engagement and systematic education to titrate fio and peep can be achieved in a resource poor setting and may decrease the incidence of hyperoxia in critically ill patients. availability of blood gas monitoring and knowledge of interpretation was a major barrier to oxygen titration tracheal intubation (ti) in adult burn patients might be unnecessary in to % of cases [ , ] . in pediatric burn patients, there is little data on both the rate of ti and the rate of early extubation [ ] . it has been common practice for a child with a facial burn and/or a suspected airway injury to be intubated early due to the risk of losing airway patency. however this risk should be mitigated against the potential risks of ti and mechanical ventilation in children. therefore the aim of this study was to describe the airway status of child burn victims taken in charge of in our pediatric burn intensive care unit. focused on patients arriving with ti, we investigated the rate of early extubation. in addition we compared non intubated patients with those with prolonged ti. this retrospective study described a cohort of patients hospitalized between and . data was retrospectively recorded from the patient's paper clinical chart. the mean age of our patients was . ± . years [mean±sd] with an average burn area of ± %. % had scald burns and % had facial burns. % of the children were admitted in the burn icu with ti. for % of them, tracheal tube was removed within the first hours after admission. the probability of prolonged ti increased independently with the burned skin area (bsa) (p < . ), the presence of facial burns (p = . ), and in case of flame burns (p = . ) ( figure ). among patients with more than % bsa, % were intubated more than h. among patients with less than % bsa, . % were intubated more than h. according to our retrospective data, it seems appropriate to intubate children with % and more bsa, while for patient with less than % bsa, it might be relevant to seek guidance from physician of the nearest burn center. under % bsa, ti seems rarely required. an analysis of the predictive applicability of initial blood gas parameters for the need for intubation and the presence of inhalation injury in patients with suspected inhalation injury c pirrone , m chotalia , t mangham , r mullhi , k england , t introduction: we hypothesise that initial blood gas parameters have a good predictive applicability in detecting the need for intubation and the presence of inhalation injury in patients with suspected inhalation injury. to the best of our knowledge, this has not been directly studied in the literature. patients with suspected inhalation injury admitted to the icu at queen elizabeth hospital, birmingham between april and may were included. the initial blood gas parameters analysed were pao (kpa), paco (kpa), ph, carbon monoxide level (cohb; %) and pao /fio (pf) ratio. receiver operator characteristics (roc) for these parameters were plotted against the need for intubation for more than hours and the presence of inhalation injury as detected by bronchoscopy and laryngoscopy. area under the curve (auc) for each parameter was calculated. results: patients were admitted with suspected inhalation injury to the icu. % were intubated for more than hours. of patients who were intubated, % had inhalation injury as indicated by bronchoscopy or laryngoscopy. table outlines the auc for initial blood gas parameters in detecting the need for intubation for more than hours and the presence of inhalation injury. ph was the parameter with the most prominent auc, with reverse correlation indicating fair accuracy. no clear inflection point was identified, although all patients with ph < . required intubation and had inhalation injury. paco had a fair predictive applicability in detecting the need for intubation. pf ratio, pao and cohb had poor accuracy. conclusions: initial blood gas parameters had a broadly poor predictive applicability for the need for intubation and the presence of inhalation injury in patients with suspected inhalation injury. severe acidosis (ph < . ) was the most useful blood gas parameter. clinicians should be cautious in using blood gas parameters alone to inform intubation decisions. lung cancer surgery is associated with a high rate of pulmonary complications including ards and mandates lung protective ventilation strategies [ , ] . such strategies include non-intubated video assisted thoracic surgery (nivats) with spontaneous breathing [ ] . currently neither data on respirator settings nor on gas exchange have been reported for applying the latter. this data constitutes a prerequisite for meaningful evaluating the respiratory consequences of non-intubated spontaneous breathing during lung cancer surgery. the aim of this case series was for the first time providing such data from lung cancer surgery including pneumonectomy. during a month period patients without contraindications [ ] scheduled for video assisted thoracic surgery (vats) for non-anatomical and anatomical lung resection including one pneumonectomy (px) were offered non-intubated spontaneous breathing. all patients gave informed written consent to the procedure as well as for analysis and publication of data. anaesthetic management included target controlled infusion of propofol and remifentanil, laryngeal mask airway, and pressure support ventilation. we present early data that early trials of cuff deflation within hours of tracheostomy insertion can be achieved using a standardized protocol. its impact on length of stay, duration of ventilation and patient-centered outcomes needs to be investigated in larger multi-centre trials. preventing underinflation of the endotracheal tube cuff with a portable elastomeric device. a randomized controlled study je dauvergne , al geffray , k asehnoune , b rozec , k lakhal hopital laënnec -chu de nantes, service d´anesthésie-réanimation, nantes, france; hotel-dieu -chu de nantes, service d´anesthésieréanimation, nantes, france critical care , (suppl ):p the management of the endotracheal tube cuff pressure (p cuff ) is routine practice for critical care nursing staff. underinflation could lead to ventilator-associated pneumonia [ ] whereas overinflation exposes to tracheal damage [ ] . multi-daily check and adjustment is recommended to ensure that p cuff lies between and cmh o [ ] . to automate this task some devices exist but may be inconvenient, bulky and/or ineffective. their use is not supported by guidelines. a portable elastomeric device could be appealing for p cuff automated regulation. this prospective randomized controlled study tested whether the tracoe smart cuff manager tm reduced the rate of patients undergoing ≥ episode of underinflation (p cuff < cmh o), as compared with routine manual p cuff adjustment. monocentric, randomized controlled study. patients with acute brain injury and receiving mechanical ventilation were prospectively allocated to one of the two arms: manual reading and adjustment of p cuff at least every h (routine care) or adjunction of the smart cuff manager tm (intervention). this study was approuved by an institutional review board. among randomized patients (routine care in , smart cuff manager tm in ), measurements were performed in h. with routine care, a higher rate of patients experienced at least one episode of underinflation ( . vs. . %;p< . ). episodes of underinflation episodes ( % vs. %;p< . ) and manual adjustments ( % vs. %;p< . ) were more frequent with routine care. for overinflation, there was no between-arms difference (p> . ). the adjunction of continuous p cuff control with the tracoe smart cuff manager tm reduced the incidence of p cuff underinflation as compared with manual intermittent adjustments. overinflation was not promoted by this device. direct laryngoscopy as a technique for tracheal intubation is a potentially lifesaving procedure that healthcare professionals in a variety of fields are taught. however, this skill is challenging to acquire and difficult to maintain. poorly performed intubation technique can lead to potentially serious complications [ ] . the intersurgical iview video laryngoscope is a new intubation tool which may have advantages over direct laryngoscopes, such as the macintosh, in the hands of novice personnel. a prospective randomized counterbalanced trial of medical students, who did not have previous airway management experience, was conducted. each student received brief didactic teaching,following this, participants were directly supervised performing laryngoscopy and intubation using the macintosh and iview devices in an alternating pattern. students were permitted up to three attempts to successfully intubate under four conditions, three laryngoscopy conditions using alaerdal intubation trainer and one using a laerdal simman manikin. there was no significant difference in the success rate of intubation or time to intubation between the two devices. the iview outperformed the macintosh in time to intubation in the normal airway in the final scenario, once students gained experience with both devices. no significant difference was found in the number of optimisation manoeuvres, or intubation attempts between groups. areas where the iview outperformed the macintosh included severity of dental trauma and participants' perception regarding ease of use ofthe device. the iview may prove to be a useful teaching tool for novice personnel who are acquiring the skills of tracheal intubation. patients with a primary pulmonary pathology were more likely to respond to aprv. this association has not been described before and warrants further multi-centre exploration in a larger patient group. introduction: airway suctioning is common during mechanical ventilation, using either an open endotraqueal suctioning or closed endotracheal suctioning (ces). closed circuits were developed to prevent arterial desaturation and atelectasis associated to ventilator disconnection. however, ces may cause substantial loss of lung volume. the purpose of this study was to investigate the effects of a compensation method to prevent the loss in aeration during ces. the suctioning technique was performed for seconds, negative pressures limited at mmhg. closed suction catheters with fr (halyard health, georgia, eua) were used. electrical impedance tomography (eit) monitoring and arterial blood gas were collected. a nihonkoden mechanical ventilator (nkv , california, eua) was applied, having a newly developed algorithm for suctioning which overcomes any pressure loss during suctioning (inlinesuction-app). when activated, the app delivers pcv ventilation, adding cmh o of end-expiratory pressure above peep, and delivering driving pressures of cmh o. results: pigs ( ± . kg) with injured lungs and mechanically ventilated. we tested the aspiration procedures using low peep= cmh o, or high peep=± . cmh o with v t o), whereas maintenance of compliance was observed when the app was on (from . ± . ml/cmh o to . ± . ml/cmh o. blood gas in a representative animal showed a drop in pao when app was off (from , to mmhg after min, and to mmhg after min) ( figure ). with app on the pao changed from (pre-suction), to ( min), to mmhg ( min). the new nksoftware, delivering pcv ventilation during suctioning, could prevent atelectasis and functional loss associated to the procedure. tyrosine kinase inhibitor: an effective tool against lung cancer involvement responsible for acute respiratory failure in icu y tandjaoui-lambiotte patients with advanced-stage non-small-cell lung cancer have high mortality rates in the intensive care unit (icu). in the last two decades, targeted therapies have changed the prognostic of patients with lung cancer outside the icu. the fast efficacy of targeted therapies led some intensivists to use them as rescue therapy for icu patients. we performed a national multicentric retrospective study with the participation of the grrroh (groupe de recherche en réanimation respiratoire en onco-hématologie). all patients with non-small-cell lung cancer admitted to the icu for acute respiratory failure between and were included in the study if a tyrosine kinase inhibitor was initiated during icu stay. cases were identified using hospital-pharmacies records. the primary outcome was overall survival days after icu admission. results: thirty patients (age: +/- years old) admitted to a total of icus throughout france were included. seventeen patients ( %) were nonsmoker. adenocarcinoma was the most frequent histological type (n= , %). most patients had metastatic cancer (n= , %). epithelial growth factor receptor mutation was the most common oncologic driver identified (n= , %). during the icu stay, ( %) patients required invasive mechanical ventilation, ( %) catecholamine infusion, ( %) renal replacement therapy and one ( %) extracorporeal membrane oxygenation. eighteen patients ( %) were discharged alive from icu and ( %) were still alive after days (see figure) . moreover, patients ( %) were alive one year after icu discharge. despite a small sample size this study showed that, in the context of lung cancer involvement responsible for acute respiratory failure, the use of tyrosine kinase inhibitor should not be refrained in patients with severe condition in icu. the burned patient is one of the most complex patients whith a very high mortality. those patients with inhalation injury have a worst prognosis, typically associated with respiratory complications. the aim of our study is to evaluate the mortality of burn patientes with inalation injury in a critical burn unit. a prospective, observational and descriptive study was conducted over a period of years. inhalation injury was defined with these criteria (≥ ): history of injury in an enclosed space, facial burns with singed nasal hair, carbonaceus sputum and stridor. if they were intubated it was diagnosed by bronchoscopy. demographic data, tbsa, absi, baux score, apache ii, sofa, mechanical ventilation (mv), complications, length of stay, hospital course and mortality data were collected. results: burns patients were admitted. % ( patients) had inhalation injury. mortality among patients with inhalation injury was , % ( patients). most patients were men and those who died were older and with higher severity scores (fig. ) . we found no significant differences between groups in the need for mv ( % vs. %) or in the percentage of tracheostomy performed ( . vs. . ). however, patients who died had more respiratory complications like ards, and also shock, renal failure and need of renal replancement therapies although infectious complications were similar in both groups. there was no statistically significant difference in volume used during initial resuscitation in the different groups. patients with inhalation injury who died had higher severity scores at the begining. although there were no differences in the need for mv patients who died had more respiratory complications as well as shock, renal failure and need of rrt, but no infectious complications.the volume used during inicial resuscitation, that was always related to the prognosis, was similar in both groups. further studies are needed to see if this greater initial severity corresponds to the degree of inhalation. aerogen, medical affairs, galway, ireland; aerogen, science, galway, ireland critical care , (suppl ):p patients with acute exacerbations such as asthma are prescribed aerosol therapy from presentation in the emergency department to progression through to the intensive care unit. however, the variability in dose delivery to the lung across the possible patient interventions is not well characterized. here, we assess the predicted lung dose of a bronchodilator in a simulated spontaneously breathing adult patient via both facemask and nasal cannula, and via tracheostomy during mechanical ventilation. a standard dose of . mg in . ml salbutamol was aerosolized using the aerogen solo nebulizer (aerogen, ireland). for facemask testing, the nebulizer was used in combination with the aerogen ultra with lpm supplemental oxygen flow. for nasal cannula testing, the nebulizer was used in combination with the airvo system (fisher and paykel, nz) system at both and lpm gas flow rate. tracheostomy-mediated ventilation was assessed in combination with a hme, with the nebulizer placed between the hme and the tracheostomy tube. international standard iso adult breath settings (vt ml, bpm , i:e : ) were used across all tests, and generated using a breathing simulator (asl , ingmar medical, usa) or mechanical ventilator (servo-u, maquet, sweden). the dose delivered to the lung was assessed using a capture filter at the level of the trachea, with drug mass determined using uv spectrophotometry at nm and interpolation on a standard curve. the results of testing are illustrated in figure . the bronchodilator dose delivered to the simulated patient was seen to be relatively consistent between progressive interventions, except during high flow therapy, with the more clinically relevant lpm gas flow rate having a profound effect on the dose. these results may go some way towards explaining how different patient interventions can affect aerosol dose. the the mechanical ventilation (mv) have been identified as an independent factor indicating a worse prognosis for lung cancer patients [ ] . this study was conducted in order to assess the results of noninvasive mechanical ventilation (niv) and/or invasive mechanical ventilation (imv) modalities in lung cancer patients admitted to the icu with acute respiratory failure (arf). in this study, lung cancer patients with respiratory failure who were admitted to the icu between january and december were evaluated retrospectively. results: patients were included in the study. the mortality rate was . %. patients had niv. imv was applied to patients. in the first hours, of the patients who were initially treated with niv were administered imv. the duration of hospital stay, diagnosis of pneumonia and mortality rate were found to be significantly lower in patients treated with niv alone (p≤ . , p= . , p= . ), but glaskow coma score (gcs) was significantly higher in this group (p≤ . ). the mortality rate was similar between the patients who were initially treated with imv and those who were treated with imv in the first hours. charlson comorbidity index (cci) and mv duration were significantly higher in patients who died (p= . , p= . ), but gcs was significantly lower in this group (p= . ). in the linear regression model for the likelihood of mortality, ccl≥ and unsuccessful niv increased the mortality rate by . ( . - . ) and . times ( - . ) respectively (p= . , p= . ). niv has been an effective modality for respiratory support in most lung cancer patients presenting with arf. however, failed niv seems to be a factor for increased mortality. therefore, the choice of respiratory support modality to be applied in this patient group should be decided by considering the gcs, cci and etiology of arf. the interaction between ventilator settings and the occurrence of acute kidney injury is not fully elucidated. this study aimed at investigating the effect of stepwise increase in peep level on the risk of acute kidney injury as evaluated with the renal resistivity index (rri).the primary outcome is to investigate whether increased levels of peep could lead to increase rri and whether rri could predict the occurrence of aki. methods: patients mechanically ventilated for at least hours and without aki at admission were included in the study. rri was calculated at icu admission. posterolateral approach was used for kidney ultrasound. the peak systolic velocity (v max ) and the minimal diastolic velocity (v min ) were determined by pulse wave doppler, and the rri was calculated as (v max -v min )/v max . the exam was performed modifying the peep levels: , and cm h o in random order for minutes. occurrence of aki was defined within days according to kdigo criteria. sixty-four patients were enrolled in the study and incidence of aki was / ( %). demographical and clinical characteristics are reported in table . increase in peep showed a significant increase in rri from peep to peep (p< . ) and from peep to peep (p= . ) ( figure ). the area under the roc curve of rri to predict aki was . at peep , . at peep and . at peep (all p< . ). the youden index analysis showed an rri> . as the best cut off for aki with a sensibility of % and a specificity of %. patients with rri> . were / ( %), / ( %) and / ( %) at peep ,peep and peep respectively. patients ventilated with a peep value associated with rri> . had higher incidence of aki ( / vs / , p< . ). the application of peep can increase intrarenal vascular resistance,which is associated occurrence of aki; peep level should therefore be balanced taking into account the rri. the rri seems able to predict occurrence of aki in mechanically ventilated patients. alveolar and respiratory mechanics modifications produced by different concentrations of oxygen in healthy rats subjected to mechanical ventilation with protective ventilatory strategy d dominguez garcia , r hernandez bisshopp , jl martin barrasa , d viera camacho , a rodriguez gil , j arias marzan , s garcia hernandez high oxygen can damage tissues [ ] . in this study, we analyze the histological and pulmonary mechanics modifications that can occur when identifying different inspiratory oxygen fractions (fio ) in lungs of healthy rats during protective mechanical ventilation. we use sprague-dawley rat. groups were designed, each with animals, the tidal volume ( ml/kg), peep ( cmh o) and respiratory rate ( rpm) were kept constant, changing the fio between the groups. four groups were established: fio . , . , . and . after hours, the lungs were removed for histological study and obtaining the wet/dry index. the histological modifications studied were: alveolar septa (as), alveolar hemorrhages (ah), intraalvelolar fibrin (if) and inflammatory infiltrates (ii). each parameter was rated from to [ ] . peak pressure (pp) and pulmonary compliance were monitored every minutes. different statistical tests will be used to analyze the data. results: references to the damage produced in the as, ah, if, ii and the global histological pattern were identified in the groups with the highest fio and there was more damage (p < . ) ( figure ). the wet/dry index rose significantly as the oxygen concentration increased (p = . ). in the groups to which a fio of . and was administered, the pp selected specific values with respect to the baseline intake from the first minutes, an aspect that was not appreciated in the other groups (p < . ). regarding pulmonary compliance, it will be seen that, in the fio . and groups, it decreased from the first minutes, finding differences with respect to the other groups (p < . ). conclusions: mechanical ventilation applied for hours in healthy animals produces disorders that are more pronounced as oxygen concentration increase. fio greater than or equal to . should be avoided without clinical justification. introduction: patients requiring prolonged acute mechanical ventilation (pamv, defined as + days on mv) are sicker and incur disproportionate morbidity and costs relative to patients on short-term mv (stmv, < days of mv). we quantified specific clinical outcomes among patients requiring pamv vs. stmv in a contemporary database. we conducted a multicenter retrospective cohort study within~ hospitals in the premier database, - . using icd- -cm and icd- codes we identified pamv and stmv patients, and compared their baseline characteristics and hospital events. because of the large sample size, we omitted hypothesis testing. a total of , patients met the enrollment criteria, of whom , ( . %) received pamv. at baseline, patients on pamv were similar to stmv with regard to age (years: . ± . pamv vs. . ± . stmv), gender (males: . % pamv vs. . % stmv), and race (white: . % pamv vs. . % stmv). pamv group had a higher comorbidity burden than stmv (mean charlson score . + . vs. . + . ). the prevalence of each of the indicators of acute illness severityvasopressors ( . % vs. . %), dialysis ( . % vs. . %), severe sepsis ( . % vs. . %), and septic shock ( . % vs. . %)was higher in pamv than stmv, as were hospital mortality and combined mortality or discharge to hospice (figure ), extubation failure ( . % vs. . %), tracheostomy ( . % vs. . %), development of c. difficile ( . % vs. . %), and incidence density of ventilator-associated pneumonia ( . / , patient-days vs. . / , patient-days). conclusions: over / of all hospitalized patients on mv require it for days or longer. pamv patients exhibit a higher burden of both chronic and acute illness than those on stmv. commensurately, all clinical outcomes examined are substantially worse in association with pamv than stmv. identifying the readiness of patients recovering from critical illness for liberation from invasive mechanical ventilation (imv) is not always straightforward [ ] . the scottish intensive care society (sics) trainee audit conducted a scotland-wide study to understand current practices relating to liberation from imv. data were prospectively collected on patient demographics, indication for intubation, spontaneous breathing trial (sbt) practices, physiological markers, icu outcome and icu los. all patients > years ventilated with imv for > hrs from the st nov. - th nov. were eligible for inclusion. exclusion criteria included extubation for end-of-life, death whilst intubated and presence of tracheostomy. logistic regression was performed to detect factors associated with extubation failure (ef). results were analysed via excel and stata v. . . patient benefit and privacy panel approval was granted. total population of patients were included: ( %) male and median apache score (iqr - ). ef at first attempt occurred on occasions ( . %), median icu los of days (iqr - ), mortality rate . %. the cohort successfully extubated first time had a median icu length of stay of days (iqr - ) and mortality rate of . %. methods of sbt and extubation outcomes detailed in table . no sbt prior to extubation had higher odds of ef (or . , ci . - . , p= . ); patient ventilation for < days had a three times higher odds of ef (or . , ci . - . , p= . ). these were independently associated with ef on multivariate analysis conclusions: we found a reintubation rate of . % in scottish icus. type of sbt most commonly used is divergent from the methods advocated in the literature. the lack of sbt and early extubation attempt was associated with failure, which in turn was associated with longer icu los and higher mortality. in patients undergoing prolonged invasive ventilation we hypothesise that abnormal right ventricular (rv) and left ventricular (lv) function are associated with increased -day mortality. whether changes in lv or rv function could aid in the prognostication of these patients has not been directly studied. patients admitted to the queen elizabeth hospital birmingham icu between april and july who were intubated and ventilated for more than days and had a formal transthoracic echocardiogram (tte) whilst in icu were included. abnormal rv function was defined by the presence of depressed function, dilated size or moderate to severe risk of pulmonary hypertension. abnormal lv function was defined by the presence of lv depression (lv ejection fraction £ % or grade ii or more diastolic dysfunction) or a hyperdynamic lv (formally mentioned in tte report). patients who had a neurological cause for prolonged ventilation were excluded. the primary outcome was -day mortality. categorical data is presented as % and analysed using a chi-squared test. continuous data is presented as median (iqr). results: patients required prolonged ventilation, of which ( %) had a tte. patients were aged ( - ), were % male and had a % -day mortality. the median ventilator days were ( - ) and % required a tracheostomy. abnormal rv function was present in % (n= ) and was associated with an increased -day mortality compared to normal rv function ( % vs. %, rr . [ . - . ], p< . ). lv function was abnormal in % (n= ) and was associated with an increased -day mortality compared to normal lv function ( % vs %, rr . [ . - . ], p < . ). abnormal rv function had a trend towards an increased mortality compared to abnormal lv function ( % vs %, rr . [ . - . ], p = . ). in this study, abnormal rv and lv function were present in a quarter of patients undergoing prolonged ventilation and were associated with an increased mortality. introduction: tidal volume delivered by mechanical ventilation (mv) in sedated patients is distributed preferentially to ventral alveoli, causing overdistention and associated collapse in dorsal alveoli, driving volutrauma, atelectrauma and ventilator-induced lung injury [ ] . temporary transvenous diaphragm neurostimulation (ttdn) stimulates diaphragm contraction [ ] . when used in synchrony with mv, ttdn encourages increased dorsal ventilation due to the change in pressure gradients with diaphragm contraction, mimicking a more normal physiological pattern. this may improve gas exchange and reduce injury. a pilot study was conducted using kg pigs undergoing mv in a mock icu. deeply sedated subjects were provided lung-protective volume-control ventilation at ml/kg. ttdn diaphragm contractions were delivered in synchrony with inspiration on every second breath, reducing the ventilator pressure-time-product by - % during mv+ttdn breaths. tidal volume distribution was recorded in each condition using electrical impedance tomography, and compared to never-ventilated, spontaneously breathing subjects (nv). results: dorsal ventilation changed from % during mv breaths to % during mv+ttdn breaths, compared to % in the nv group (p= . ). ventral ventilation changed from % during mv breaths to % during mv+ttdn breaths, compared to % in the nv group (p= . , figure ). conclusions: ttdn diaphragm contraction used as an adjunct to mv yields a more physiological pattern of volume distribution. this translates into less overdistension in the ventral areas and less atelectrauma in the dorsal areas and reduces ventilator-induced lung injury. this technology introduction: by measuring the pes and its derivatives, we can measure the relationship that exist between the diaphragmatic excursion and the oscillation of the esophageal pressure curve: pswing (ps) so we infer that, just as with the pes, the variations of it might be related to a weaning failure [ , ] . however, no nominal value exists in the bibliography to predict the test result. patients who meet with the inclusion criteria start the weaning process through a test of minutes of spontaneous ventilation, t-tube (tt). and also the respiratory rate (rr) and the tidal volume (tv). from this analysis, an average ps (aps) is determined for each moment of the test (aps , initial and aps , final.).a quotient was obtained in relation to these variables using the value previously obtained (quotient dtv/dps x . a total of patients were included (n= ).regarding the evolution during tt, (n= ) ( %) were successful, while (n= ) ( . %) failed when analyzing a rate that relates the variables tv and ps, a quotient was obtained in relation to these variables using the value previously obtained (quotient dtv/dps) for patients who were successful and who failed, (dtv/dps)/ successful patients presented a value of . while those of the failure group presented a value of . , (or , - p= . ) ( table ) . when presenting the relationship between tv and ps through the quotient (dvt/dps)/ , it is observed a tendency to have a higher quotient among patients who failed versus those who did not fail. the process of weaning from mechanical ventilation imposes an additional workload on the cardiovascular system, which may result in impaired myocardial function, increase in left ventricular filling pressure and respiratory distress. among surgical patients, those undergoing heart surgery are particularly susceptible to cardiac dysfunction induced by weaning because of inadequate cardiovascular reserve. the aim of our study was to depict the pathophysiological changes assessed by echocardiography during the steps of weaning and to identify possible predictors of weaning failure (wf). we enrolled consecutive patients undergoing isolated coronary artery bypass grafting in our institution. data were obtained by intraoperative transesophageal echocardiography before sternotomy (t ) and by transthoracic echocardiography at the beginning of weaning (t ) and at the time of extubation (t ). wf was defined as deferral of planned extubation or respiratory failure needing reintubation or non-invasive mechanical ventilation within hours. results: wf occurred in patients ( . %) and involved manifestations of respiratory distress in ( . %). we found a significant association between left ventricle outflow tract-velocity time integral (lvot-vti) and ventricular-arterial coupling measured at t and wf, with lvot-vti emerging as the best predictor of wf with an area under roc curve of . ( figure ); an optimal cutoff value of cm provided % sensitivity and % specificity. significant increase in e/e' measured at t ( . vs . , p . ) suggested a cardiac etiology of respiratory distress in patients who failed the weaning trial. our study showed that serial assessment of hemodynamic parameters by means of echocardiography is feasible in cardiac surgical patients and can provide insight into pathophysiological changes during weaning. although these preliminary data need to be confirmed in a larger population sample, lvot-vti emerged as a promising predictor of subsequent wf. compliance with guidelines for respiratory therapy in preclinical emergency medicine g jansen, n kappelhoff, s rehberg protestand hospital of the bethel foundation, anaesthesiology, intensive care and emergency medicine, bielefeld, germany critical care , (suppl ):p introduction: current guidelines on pre-hospital emergency ventilation are based on the guidelines for lung protective ventilation in the intensive care unit. the present survey was designed to determine the accordance of actual pre-hospital emergency ventilation by german emergency physicians (gep) with these recommendations. recommendations include a respiratory rate (rr) between - /min, a tidal volume (vt) between - ml/kg, a maximum pressure (pmax) < mbar and a positive end-expiratory pressure (peep) of mbar. an anonymous web-based questionnaire encompassing questions was sent to gep from september to december of . gep were asked to specify their level of education, their preferred ventilation settings and the usually chosen parameters employed to guide mechanical ventilation. statistical analysis was performed using the ch²-test with a significance level ≤ . . % of the questionnaires were completed ( / ). % of the participants were trainees (tr), % consultants (co). as target parameters for guidance of ventilation, % of the tr and % of the co use capnometry. the vt controlled % of the tr and % of the co on the basis of body weight. % of the tr and % of the co reported to control oxygenation using spo . table shows our analysis of the given answers. there were no statistically significant differences between the groups. deviations from the guidelines of pre-hospital emergency ventilation settings are common and mainly concern the use of a guidelinecompliant peep. in addition, recommended target parameters for guidance of ventilation were not applied in a significant proportion of gep. prospective observational study including ltx recipients admitted to our icu from february to january , who underwent a spontaneous breathing trial (sbt) using a t-piece for minutes. clinical variables and arterial blood gas samples were recorded before starting sbt and after minutes on the t-piece. diaphragmatic excursion (de) and thickening fraction (dtf) were also assessed using ultrasound(us) after minutes on the tpiece. us-dd was defined as de< mm or dtf< . of at least one hemidiaphragm. patients who successfully completed a sbt, defined according to clinical criteria,were extubated. extubation failure was defined as the need for reintubation within h. results are expressed as medians (iqr) or frequencies (%). ltx recipients were admitted to the icu, of whom underwent an sbt. were male, and the median age was y. main indications for ltx were interstitial lung disease ( . %), copd and cystic fibrosis. were bilateral ltx, and and were left and right unilateral ltx respectively. patients were extubated after sbt and required reintubation within h. presented us-dd, though there were no differences between patients who succeeded and those needing reintubation. in contrast, patients who succeeded showed higher pao /fio after minutes on the t-piece (table ) . similarly, higher reductions in deltapao /fio after minutes on the t-piece were observed in patients who failed. oxygenation after sbt performed using a t-piece may predict extubation failure in ltx recipients with successful sbt. us-dd was not associated with the need of reintubation. descriptive study about the relationship between self-extubation episodes and patient-ventilator interaction s nogales , introduction: to evaluate the relationship between self-extubation and patientventilator interaction, among other physiological variables, in order to predict and to prevent these events. self-extubation (se) are quality indicators in patients under invasive mechanical ventilations (imv) and are related with mortality [ ] . planned secondary analysis of a prospective data base of clinical and physiologic signals of patients receiving imv. we included se episodes ( - ) with continuous record of ventilator and monitor signals (bclink bettercare®). we analysed demographic data, physiological parameters (peripheral oxygen saturation spo , heart rate hr, respiratory rate rr and media arterial pressure map) and patientventilator interaction (asynchrony index ai, ineffective efforts during expiration iee and double cycling dc). we studied a period of hours prior to the se episode. we used the wilcoxon non-parametric test and for a proper analysis a linear mixed effects model. we included episodes of se, mean age ± years, %men, apache ii at admission ± , , ± , days under imv until the episode, reintubation rate . %, icu stay , ± , days, icu mortality %. at the time of the se, % were under sedation, % with physical restraint. the % were in weaning. we observed a trend to increase in spo , rr, hr, map and asynchronies in the -hour period prior to se episode. we compared these variables from this period with a -hour period before and we observed a statistically the data presented in this study show that our results are in accordance with the literature with favorable mortality and early postoperative complication rates and support that this procedure is an excellent alternative for surgery in the elderly patients. it is reported that patients with pulmonary hypertension (ph; systolic pulmonary arterial pressure (spap)≥ mmhg)) have frequent cardiac complications after transcatheter aortic valve implantation (tavi). ph often gets worse in some patients despite the normal cardiac function after tavi. no studies have ever examined prognosis after tavi in patients with or without worsening of ph. therefore, we retrospectively examined the frequency of mid-to long-term heart failure and cardiac death in patients with and without deterioration of ph after tavi. among patients who underwent tavi at our hospital between february and march , we analysed patients with ph (spap≥ mmhg) before surgery. spap was measured in transthoracic echocardiography before and within week after tavi. patients were divided into two groups according to whether spap worsened/ did not change or improved after tavi. we examined the frequency of admission due to heart failure or cardiac death (death caused by heart failure, angina, or myocardial infarction) during the period of years after tavi. ph worsened or did not change after tavi in patients, while it improved in patients. the left ventricular ejection fraction measured within week after tavi showed no difference between the two groups ( . ± . % vs . ± . %, p= . ). the worsened/ no change group was higher in frequency of admission due to heart failure (logrank; p< . ) and cardiac death (logrank; p< . ). despite successful treatment for as by tavi, the frequency of heart failure and cardiac death was higher in patients who did not show improvement of ph after tavi, even in the absence of cardiac function decrease. vigorous intervention for ph worsening after tavi may be helpful to improve prognosis. the there are several different anti platelet drugs that can be used to treat acute cardiac events. currently there are no effective markers that can assess how these drugs modify coagulation profile and quality. a new functional biomarker that measures fractal dimension (df ) and clot formation time (tgp) has been developed [ ] . df quantifies clot microstructure whereas tgp is a real-time measure of clotting time. we aimed to validate df and tgp in st elevation myocardial infarction (stemi) and assess the effect of two p y inhibitors which have different pharmacological mechanisms: clopidogrel and ticagrelor. we prospectively recruited stemi patients in the emergency setting. venous blood samples were collected hours after admission, following treatment with either ticagrelor or clopidogrel, in accordance with the local guidelines at the time. the blood samples were tested using the df and tgp biomarker, platelet aggregometry, clot contraction and standard markers of coagulation. results: patients received clopidogrel and received ticagrelor. the df for clopidogrel was higher than ticagrelor ( . ± . vs . ± . , p= . which corresponds to a decrease in clot mass of % figure ) and the tgp was reduced ( ± sec vs ± sec, p= . a % reduction in time). the results of the study suggest that clopidogrel is less powerful in its effects on clotting characteristics compared to ticagrelor. blood from patients receiving clopidogrel formed quicker and denser clots. this would suggest the risk of secondary events or stent occlusion is lower in those patients on ticagrelor, highlighting that df and tgp may be important in identifying patients at risk of future thrombotic events, the study is ongoing and will investigate the long term outcome in these patients. introduction: new onset atrial fibrillation (noaf) during critical illness frequently resolves prior to discharge. however long-term risks of noaf (i.e. heart failure, ischemic stroke and death)remains high [ ] . previous studies noted that nearly half of noaf cases did not have diagnosis recorded [ ] . addressing this may reduce post critical illness mortality by increasing af surveillance post intensive care (icu) discharge. retrospective data was collected from an electronic health record for icu admissions over a month period from a biomarker is defined as a measurable indicator of some biological state or condition. combined with a good clinical evaluation, they can enable an early and safe diagnostic, thus a faster management for the patient. cardiac biomarker testing is not indicated in routine in the emergency department (ed) because of low utility and high possibility of false-positive results. however, current rates of testing are unknown. the aim of our study was to evaluate the importance of measuring cardiac biomarkers especially troponins, d-dimer, and btype natriuretic peptide in our daily practice, and to identify the latest recommendations for a better use of these biomarkers in the diagnostic and therapeutic approaches. we conducted a prospective observational study, over a months periods performed in the ed of the university hospital center ibn rochd, casablanca, morocco, including all patients admitted during our study period and having a blood test for at least one biological marker. the dataset was analyzed by spss statistics . . a total of patients was enrolled. troponins were tested in . % patients (high sensitive in . % and troponin i tni in . %), ddimer in . %, bnp % and nt pro bnp in . % of cases. the diagnostic impact was significant in . % of cases for troponins, . % of cases for d-dimer and . % for bnp. the therapeutic impact was considered important in . % cases for troponins, . % for ddimer and . % for bnp. cardiac biomarkers have an important role in the ed, not only do they confirm the diagnosis (including the role of troponins in acs) but also eliminate others (with a strong negative predictive value of d-dimer for thromboembolic disease) and prove the cardiopulmonary origin of acute dyspnea (the significant place of bnp in confirming the diagnosis of acute heart failure). a multicenter study on the comparison of inter-rater reliability of a new and the original heart score among emergency physicians from three italian emergency departments the heart (based on history,ecg,age,risk factors,troponin) score is a valid tool to stratify the acs in chest pain. but some reports suggest that its reliability could be low for heterogeneity in the assignment due to the subjective interpretation of the history. we used the chest pain score for the "history". in this study we compare the reliability of the new heartcps and original heart. this is a multicenter retrospective study conducted in italian ed between july and october using clinical scenarios. ten physicians were included after a course on heart and heartcps score. we used scenarios which included clinical and demographic data. each participant independently assigned scores to the scenarios using the heart and heartcps. we tested the interrater agreement using the kappa-statistic (k), the confidence intervals are bias corrected ; we used stata/se . statistical software . a p-value of < . defines statistical significance. the overall inter-rater reliability was good for heart and heartcps: kappa = . (ci %; . - . )and , (ci %; . - . ); with good agreement among all the class of risk for heartcps but moderate in the medium class for heart . we found significant differences of inter-rater reliability among the senior and junior physicians who used the heartcps:k= . (ci %; . - . )and . (ci %; . - . ). heartcps score increased its history inter-rater reliability specially among the junior physicians from k= . (ci %; . - . ) to k= . (ci %; . - . ).the junior physicians seem to be more reliable than senior with the heartcps:k= . ( . - . ) vs k= . (ci %; . - . ). the heartcps showed inter-rater reliability better than original heart among the medium class of risk and the junior group. it could be proposed to young doctors to stratify the acs risk of chest pain. limit: we used scenarios rather than real patients. a hybrid approach as treatment for coronary artery disease: endo-cabg or pci first, does it matter? introduction: the aim of this study is to discuss the short-term results of a hybrid approach combining minimally invasive endoscopic cabg (endo-cabg) with a percutaneous coronary intervention (pci). to bypass the disadvantages and potential complications of conventional cabg via median sternotomy, we developed the endocabg technique to treat patients with single-and multi-vessel coronary artery disease (cad). this procedure is performed with three -mm thoracic ports and a mini-thoracotomy utility port ( cm) through the intercostal space. this technique can be combined with pci: the hybrid approach. the sequence of the procedures (endocabg followed by pci or vice versa) may result in different outcomes. from / to / data from consecutive patients scheduled for a hybrid technique at jessa, belgium, were prospectively entered into a customized database. this database was retrospectively reviewed. subgroup analysis was performed to compare outcomes of patients who first received endocabg with patients who first received pci. a p-value < . is considered significant, a p-value < . is considered as a trend toward significance. four patients underwent revision surgery and patients died within the first days. in patients the left anterior descendens artery (lad) was grafted with the left internal mammary artery (lima), the right coronary artery (rca) was the most stented vessel using pci. patients first treated with pci received more units of fresh frozen plasma after endocabg compared to those who were first treated with endocabg (p= . ). there was also a trend toward significant more transfusion of packed cells in this small subgroup (p= . ). the hybrid approach is a feasible technique as a treatment option for patients with multi-vessel cad. if cabg follows the pci, patients are more likely to receive transfusion. a possible explanation could be the need for dual antiplatelet therapy prior to surgery in this group, but this needs further investigation. prognostic difference between troponin elevation meeting the mi criteria and troponin elevation due to myocardial injury in septic troponin t (ctnt) elevation in critically ill patients is common and is associated with poor outcome. using common assays, - % of patients in the icu will have elevated troponin level. our aim was to determine whether there is any prognostic difference between troponin elevation meeting the mi criteria (rise and fall more than % together with echo and ecg new abnormalities) and troponin elevation due to myocardial injury in septic patients. we enrolled patients with sepsis and mean sofa score , respectively in which ctnt level was measured more than once and analyzed there ecg and echo findings. patients were classified into three groups:definite mi (rise and fall ctnt ≥ % and contemporaneous changes on ecg and/or echo),possible mi (rise and fall ctnt ≥ % and no other findings),myocardial injury (ctnt rise less than %) results: data from patients were analyzed ( % female; mean age . (sd . )). a total of patients had at least one elevated ctnt more than . mkg/l. in ( %) of patients ctnt level rised more than % from the first elevated measurement. ( %) of patients met mi criteria considering new ecg and echo findings. the overall mortality rate in all patients was . %.the mortality rate didn't differ significantly in three groups: in the definite mi group . %, in the suspected mi group %, in the non mi ctnt elevation group , %, p= , . coronary angiography was performed in ( %) of patients from the definite mi group,pci was performed in ( %) of patients. the mortality rate in the invasive group was not significantly lower comparing to the nonivasive group % vs , %, p= , . bleeding complications were significantly more frequent in the definite mi group % vs % and % respectively conclusions: ctnt level elevation is associated with poor outcome regardless coronary or non coronary injury. myocardial revascularization may be beneficial in patients with sepsis and definite mi, but it is also associated with increased bleeding risk. diagnostic interest of "marburg heart score" in patient consulting the emergencies department for acute chest pain chest pain is a common reason for emergency department visits, although this primarily refers to acute coronary syndrome (acs), this symptom may be frequently related to other non-ischemic etiologies. the aim was to validate the marburg heart score as a tool to exclude coronary artery disease in emergency department patients with nontraumatic acute chest pain. methods: a prospective, observational, descriptive and analytic cohort study conducted in the emergency department, from february st to march st, , collecting patients consulting for nontraumatic acute chest pain, the "marburg heart" score was calculated for all these patients. telephone contact was made after weeks to look for an ischemic cardiovascular event. we included patients. the mean age was +/- years, the sex ratio was . . the majority of the patients ( . %) consulted directly to the emergency department, . % were referred by a primary care physician. the median time to consultation after the onset of chest pain was hours. high blood pressure was the most common risk factor ( . %), followed by smoking ( %), diabetes ( . %) and dyslipidemia ( . %). thirty-five patients ( . %) had already coronary heart disease, ecg was pathological in . % of patients, patients had an acs with st segment elevation. at six weeks, . % of the patients had an acute coronary event. according to the patients' answers on the questions of the marburg heart score. the area under the roc curve of this score was . with a negative predictive value of . %; the "marburg heart score" is a simple, valid and reproducible clinical score with a discriminatory power to rule out the diagnosis of coronary artery disease from the first contact with the patient presenting for chest pain in emergencies. the abdominal aortic aneurysm (aaa) surgery is a complex procedure in elderly patients with high cardiovascular risk. anesthesiological techniques should play special attention to the volume status during cross-clamping as well as to the blood loss. goal directed fluid therapies (gdt) in aaa surgery in elderly patients decrease the perioperative morbidity and mortality [ ] . aim of this study is to investigate administration of fluid-based on either a gdt approach or a control method (fluid administered based on static preload parameters and traditional hemodynamic) in all phases of aaa surgery and especially in the phase of clamping and de-clamping. a total of patients asa iii, randomly scheduled for elective, open aaa surgery were included in this clinical trial. they were randomly assigned to two groups i -gdt with targeting stroke volume variation (svv) and ii -control group where fluids were administered at the discretion of the attending anaesthesiologist. in both these groups hemodynamic parameters, central venous pressure (cvp), temperature, blood loss and diuresis were registered during the operation and hours postoperatively. each group was assessed for postoperative complications. gdt group received less fluids and had a higher cardiac index (ci) ( . ± . vs. . ± . l/minute per m , p < . ) and stroke volume index ( . ± . vs. . ± . ml/m , p < . ) than the control group. there were significantly fewer complications in the intervention than control group ( vs. , p = . ). gdt fluid administration enables less use of fluids, improved hemodynamic and fewer postoperative complications in elderly patients undergoing aaa surgery. ultrasonography is a valid diagnostic tool, used to measure changes of muscle mass. the aim of this study was to investigate the clinical value of ultrasound-assessed muscle mass, in patients undergoing cardiothoracic surgery that present muscle weakness postoperatively. for this study, consecutive patients were enrolled, following their admission in the cardiac surgery intensive care unit (icu) within hours of cardiac surgery. ultrasound scans, for the assessment of quadriceps muscle thickness, were performed every hours for days. muscle strength was also evaluated in parallel, using the medical research council (mrc) scale. of the patients enrolled, ultrasound scans and muscle strength assessment were performed in patients. the muscle thickness of rectus femoris (rf), was slightly decreased by . % ([ %ci: - . ; . ], n= ; p= . ) and the combined muscle thickness of the vastus intermedius (vi) and rf decreased by . % ([ % ci: - . ; . ], n= ; p= . ). patients whose combined vi and rf muscle thickness was below the recorded median values ( . cm) on day (n= ), stayed longer in the icu ( ± vs ± hours, p = . ). patients with mrc score ≤ on day (n= ), required prolonged mechanical ventilation support compared to patients with mrc score ≥ (n= ), ( ± vs ± hours, p = . ). the use of muscle ultrasound seems to be a valuable tool in assessing skeletal muscle mass in critically ill patients after cardiothoracic surgery. moreover, the results of this pilot study showed that muscle wasting of patients after cardiothoracic surgery is of clinical importance, affecting their stay in icu. prediction of cardiac risk after major abdominal surgery s musaeva, i tarovatov, a vorona, i zabolotskikh, n doinov kuban state medical university, anesthesiology and intensive care, krasnodar, russia critical care , (suppl ):p the aim is to assess the incidence of cardiovascular incidents in major abdominal surgery [ ] using the revised lee index. a study was conducted of elderly patients who underwent major abdominal surgery in the krasnodar regional clinical hospital no. under combined anesthesia. in the preoperative period, the risk of cardiovascular incidents was assessed using the revised lee index and the functional status was assessed by met. depending on the lee index, groups were identified: group (n = ) -low risk (index value - ), group (n = ) -intermediate risk (index value - ); group (n = ) -high risk (index value> ). we estimated the incidence of critical incidents in groups: hypo-, hypertension, arrhythmias, and bradycardia. in the general population, cardiac risk was . ± . points; functional status - . ± met. the greatest number of critical incidents was recorded in patients with high risk ( . %), the smallest -in patients with low risk ( . %), in patients with intermediate risk - . % (n < , between groups according to chi-square criterion). in the structure of critical incidents, hypotension was most often encounteredin ( %) patients, while some patients revealed several incidents from the circulatory system (n = ). overall, the lee scale showed good prognostic ability (auroc = . ) in predicting hemodynamic incidents. the revised lee index is a useful tool to help assess the risk of cardiovascular incidents and determine patient management tactics in the perioperative period. postoperative cognitive dysfunction (pocd) remains an unresolved problem due to lack of consensus on its etiology and pathogenesis. some believe that pocd is the result of the direct toxic effect of general anesthetics on the nervous system. others claim that surgical trauma activates proinflammatory factors that induce neuroinflammation. wistar rats were allocated into groups: -minor surgery (n= ), major surgery group (n= ). after days of handling and habituation rats undergone surgery under isoflurane general anesthesia ( vol.%). group rats underwent laparotomy with gentle gut massage followed by wound closure. rats in group undergone left side nephrectomy. starting from the th postoperative day spatial memory in rats was studied in morris water maze which is a cylinder metal pool with a diameter of . and a height of . m filled with water (temp. ± o c) up to half. it has a platform with a diameter of cm and a height of cm below the water level. testing was preceded by a training stage, which included sessions daily for days. thus, rats developed spatial memory to the location of the platform. on the th day of the study test stage was conducted to assess spatial memory: rats were launched from points into maze without platform and data were recorded for seconds at each session. time spent on the target quadrant (ttq) and the number of target area crossings (tac) were registered. a second test was conducted days after the first test to evaluate long-term spatial memory. the duration of surgery and anesthesia did not differ significantly between groups. there was a significant difference between groups in average ttq and tac in test (table ). in test minor surgery group showed better results but they were less significant. major surgery is associated with a more pronounced deterioration of spatial memory in rats in early postoperative period compared to minor surgery. cardiac inflammatory markers in icu patients with myocardiac ischemia after non cardiac surgery (a pilot study) p manthou , g lioliousis , p vasileiou , g fildissis national kapodistrian university of athens, athens, greece; national kapodistrian university of athens, general thoracic hospital´´sotiria´´, athens, greece; national kapodistrian university of athens, university of athens, athens, greece critical care , (suppl ):p patients with known coronary artery disease have higher perioperative risk for myocardial ischemia [ , ] . mortality is frequent following cardiac ischemia in the intensive care unit (icu) after non-cardiac surgery. the first group includes patients admitted to the intensive care unit for post-operative follow-up without myocardiac ischemia in the first hours. the second group includes patients with myocardiac ischemia postoperatively and needs intensive care monitoring. cardiac risk assessment was made with the lee index,hemorrhagic risk assessment with the has-bled bleeding score and thrombotic risk assessment with cha ds -vasc score. postoperatively, pathological test values such as bnp, troponin, crp, calcitonin were estimated. the sequential organ failure assessment (sofa) systeme was used to assess sepsis. the nursing activity score (nas) scale was used to measure the workload of various nursing activities in the icu. according to the pilot study, the sample consists of patients. . % had myocardial ischemia. the lee index was significantly higher in patients with myocardial ischemia. the duration of hospitalization, the high dose of vasoconstrictive drugs, the length of stay in the icu, the duration of mechanical stay and the nursing workload were higher in patients with myocardial ischemia. ck-mb and troponin levels differed significantly between the two groups. creatinine, bilirubin and bnp during the hours were significantly higher. patients with myocardial ischemia had significantly higher mortality. cardiac risk assessment, has-bled score and cha ds -vasc score in combination with cardiac enzymes such as troponin could predict myocardiac ischemia in severely ill icu patients. introduction: according to the literature an airway complication followed thyroid gland surgery are: difficult trachea intubation, tracheomalacia, postextubation stridor and bleeding [ , ] . most common cause of death was problem with respiration and airway obstruction [ ] . subsequent hypoxia could require emergency airway and even tracheostomy [ ] . aim of our study was to determine the most common of airway complications and their association with type of surgery in our region. the retrospective cohort study included pts., ( women, men) was performed in odessa regional hospital, oncology centre odessa. there were three types of patients: with euthyroid goiter - ( %), polynodos goiter - ( %) and thyroid cancer - ( %) ( table ) . airway complications were diagnosed after trachea extubation based on indirect laryngoscope, presence of stridor, desaturation. the pearson's criteria was calculated. the ratio of airway complications after thyroid surgery was . % ( pts). the main reasons of airway complications in thyroid surgery included: laryngeal edema - pts ( . %); recurrent laryngeal nerve injury - pts ( . %) and postoperative bleeding pts ( . %). thyroid gland cancer and polynodosal goiter associated with laryngeal edema and recurrent laryngeal nerve injury (pearsen criteria were . -moderate and . consequentially). it's may require more attention from the anesthetists after extubation and readiness for an urgent airway. serum iron level and development of multiple organ dysfunction syndrome in patients in the perioperative period s tachyla mogilev regional hospital, department of anesthesiology and intensive care, mogilev, belarus critical care , (suppl ):p recently there has been attention of researchers to the problem of perioperative anemia. it was found that it increases the risk of death and postoperative complications. threatening complication is multiple organ dysfunction syndrome (mods). the objective was to determine the level of serum iron in the perioperative period in patients with endoprosthetics of large joints, and with the presence of mods in abdominal surgery. a prospective cohort study was conducted in patients, including men and women, age . ± . years. two groups were identified: st (control) -patients after endoprosthetics of large joints (n = ), nd (main) -patients in abdominal surgery with the presence of mods (n = ). the presence of mods was established based on the criteria for the sccm / accp conference. serum iron was monitored using an au analyzer (usa). the study identified several stages: st -before surgery, nd - st day after surgery, rd - rd day, th - th day, th - th day. when studying the indicators of serum iron, its significant decrease (p < . ) in the postoperative period was established. in the st group: st stage - . ( - . ) mmol / l, nd stage - . ( . - . ) mmol / l, rd stage - . ( - . ) μmol / l, stage - . ( . - . ) μmol / l, stage - . ( . - ) μmol / l. in the nd group: st stage - . ( - ) mmol / l, nd stage - . ( . - . ) mmol / l, rd stage - , ( . - . ) μmol / l, stage - . ( . - . ) μmol / l, stage - . ( . - ) μmol / l. moreover, in both groups, iron increased at the th stage against the nd stage (p < . ). when comparing the level of iron between the groups, significant differences were found (p < . ) at the nd, rd and th stages. in patients in the postoperative period, a decrease in serum iron is observed, the level of which rises by the th day, but does not reach the initial values. this decrease is more pronounced in patients with the presence of mods after abdominal surgery. kidney and pancreatic graft thrombosis happened in . % and . %, respectively, and bleeding in . %. forty-one ( . %) developed at least one infection during hospital stay. infection during icu was found in . % and main pathogens were gram negative bacilli sensible to beta-lactam. after icu, the incidence of multi-drug resistant pathogen was . %, predominantly gram negative bacilli. fungal infection was lower %. all-cause hospital mortality rate was . %. infectious complications are the main cause of morbidity and mortality following spk transplantation. the administration of broadspectrum prophylactic antibiotics are leading to the appearance of multi-drug resistant pathogens. knowing local microbiological flora may be helpful, allowing more adequate antibiotic prophylaxis. introduction: cardiopulmonary bypass (cpb) is associated with thrombotic complications. occurrence of thrombosis after cpb is % which takes the third place between cpb-associated complications. our study determined preoperative predictors of thrombosis in children with congenital heart defects. patients with congenital heart diseases in age up to months days (median age - , months, youngest age - days after birth, oldest - months days), underwent cardiac surgery with cpb, were enrolled in this study. all patients were divided into two groups: st -without thrombosis, nd -with thrombosis. protein c, ddimer, von willebrand factor and plasminogen plasma levels were assessed directly before surgery. thrombotic cases were proven by performing doppler ultrasound or mri. thrombotic complications were diagnosed in children ( %). between all thrombotic complications ischemic strokes were diagnosed in % ( cases), arterial thrombosis in % ( cases), intracardiac thrombus in % ( cases) and mechanical mitral prosthetic valve thrombosis %( ). receiver operating characteristic (roc) curves are created for the listed indicators. area under the curve (auc) for protein c , (sensitivity(sn)- %, specificity(sp) - %), d-dimer is , (sn - %, sp %), for plasminogen activity - , (sn %, sp %) and for von willebrand factor level - , (sn %, sp %). an roc curve was created for all three indicators, the auc was . (sn - %, sp - %). these parameters can be recommended as predictors of thrombosis in children after cardiac surgery. cpb is related with a large number of life-threatening complications. in our work, preoperative predictors of thrombosis were identified. based on this data, it is possible to create thrombosis risk scale change the tactics of the anaesthetic approach, the prevention of thrombosis in the postoperative period. further studies are needed to identify other possible predictors of thrombosis. introduction: abdominal ischemia occurs in % of patients submitted to aortic aneurysm repair. its early diagnosis requires an elevated index of suspiction, particularly in more severe patients. we hypothesized that earlier increase and higher levels of c-reactive protein (crp) may help to predict intra-abdominal ischemia. we performed a retrospective study of patients admitted to the intensive care department (icd) after abdominal aorta aneurism surgery. we included all patients admitted during a two-year period, that survived for more than hours. primary outcome was splanchnic ischemia assessed by abdominal ct-scan. we also evaluated the presence of bacteremia, abdominal compartment syndrome and icd mortality. association between inflammatory parameters and ischemia was evaluated by multivariate logistic regression. introduction: crp (c-reactive protein) has been shown to be a useful biomarker in identifying complications after major abdominal surgery. gastrectomy is a high-risk surgical procedure that requires post-operative critical care support to monitor for complications which are predominantly infective in nature. the aims of this study were to determine whether there is a relationship between post-operative crp levels and patients who developed post-operative infective complications. a retrospective analysis was performed on patients undergoing elective gastrectomy for gastric cancer at a single centre between september and july . post-operative crp levels for each day following resection were analysed for all patients. roc curve analysis was used to determine which post-operative day (pod) gave the optimal cut-off. of patients included, the majority were male ( . %), mean age was . years and . % had node-negative disease. a total of patients ( . %) had an infective complication, which includes those who experienced an anastomotic leak. crp levels on post-operative day gave the greatest auc for the gastrectomy group ( . ). crp cut-off of mg/l was significantly associated with infective complications (or . , % ci . - . , p= < . ) and gave a sensitivity of % and specificity % (ppv %, npv %). more patients with a crp > on post-operative day experienced an infective complication ( % vs %, p = < . ) or a leak in particular ( % vs %, p = . ). a crp level of less than mg/l on pod may be useful to predict the development or exclude the likelihood of such infective complications in this group of patients prior to clinical signs (ppv %, npv %). this may prompt and facilitate decision-making regarding early investigation and intervention or prevent inappropriate early discharge from critical care, whilst providing more assurance in identifying those who could be stepped down to ward level care. vasoplegia is commonly observed after cardiopulmonary bypass surgery (cpb) and associated with high mortality. chronic use of reninangiotensin aldosterone system inhibitors (raasi) is associated with its incidence and ensuing need for vasopressor support after cpb. renin serves as marker of tissue perfusion [ ] . we examined the role of renin in the setting of raasi exposure and vasopressor needs in the peri-cpb period. prospective observational study of adult patients undergoing cpb, aged . ± . years ( men, women). blood was collected ) post induction, pre-cpb; ) min post cardioplegia, and ) immediately post bypass. vital signs and perioperative medications were recorded. as control, blood was collected from men and women aged . ± . , not diagnosed with lung disease and not prescribed any raasi. baseline plasma renin in cpb patients tended to be higher than in control subjects (mean= . pg/ml± . vs. . pg/ml ± . , respectively, p= . ). minutes into cpb, mean renin was increased from baseline ( . pg/ml± . , p= . ), and remained elevated immediately post cpb ( . pg/ml± . ). patients using raasi prior to cpb tended to have a larger increase in renin post cpb (delta= . pg/ ml± . ) vs. those not previously on raasi ( . pg/ml± . , p= . ). renin was elevated in patients requiring vasopressor support in the hours post cpb vs. those not requiring pressors ( . pg/ ml± . vs. . pg/ml± . p= . ). in those prescribed raasi and requiring pressors post cpb, there was a tendency toward greater renin increase than those not requiring pressors postoperatively ( . pg/ml± . vs. . pg/ml± . , p= . ). this study suggests a trend toward higher renin levels, particularly during cpb, in patients prescribed raasi, and a positive association between renin and postoperative vasopressor needs. we speculate that increased renin levels may predict postoperative vasoplegia. cardiac surgery is associated with perioperative blood loss and a high risk of allogenic blood transfusion. it has been recognized that high blood product transfusion requirement is associated with adverse clinical outcomes. guidelines on patient blood management therefor aim at reducing blood loss and blood transfusion requirements in cardiac surgery. as there remains controversy about the advantage of minimal invasive techniques on blood loss an transfusion requirements, we wanted to investigate if the average blood loss and transfusion requirement in minimal invasive endoscopic coronary artery bypass graft surgery (endo-cabg) differ from conventional technique. we assessed the influence of pre-operative anticoagulant medication for blood loss. estimated average blood loss after conventional cabg is ml (+/- ) and transfusion requirement , units packed red blood cells . we performed a retrospective cohort study of our cardiac surgical database. from / / to / / , we collected data from patients undergoing endo-cabg. we analyzed blood loss, transfusion as well as pre-operative use of anti-coagulants as a risk factor for blood loss. we found that mean total blood loss in endo-cabg does not differ from conventional cabg, nonetheless mean transfusion requirement was lower in our cohort. use of direct oral anticoagulant is aossciated with increased blood loss and transfusion requirements (table ) . total blood loss is not influenced by minimal invasive technique for cabg (endo-cabg). an explanation for the lower transfusion requirements is the use of a minimal extracorporeal circulation, which is known to reduce the risk of transfusion. another important factor is the implementation of a standardized transfusion-protocol based on available evidence. reducing transfusion requirements is an important component in improving patient outcome after cardiac surgery and is related to multiple factors in perioperative care of our patients. retinal microvascular damage associated with mean arterial pressure during cardiopulmonary bypass surgery v shipulin retinal perfusion corresponds to cerebral perfusion and it is very sensitive to hemodynamic disturbances [ , ] . we investigated the association between retinal microvascular damage and hemodynamic characteristics in patients undergoing coronary artery bypass grafting surgery (cabg) with cardiopulmonary bypass (cpb). methods: patients with coronary artery disease and systemic hypertension were examined. ophthalmoscopy and optical coherence tomography were performed before and - days after cabg. the hemodynamic parameters during cpb were analyzed. results: ( %) patients had changes in the retinal vessels and in the ganglionic fiber structure on - day after surgery: in % of patients the foci of ischemic retinal oedema appeared, in % the decrease of the thickness of ganglionic fiber were observed. these changes may be associated with intraoperative ischemia of the central retinal artery. in ( %) patients the mean arterial pressure (map) during cpb was increased up to mmhg. in ( %) of them the association between map and foci of ischemic retinal oedema were revealed. the ischemic retinal changes were observed significantly more often if the delta of map during cpb was over then mm hg compared with the patients where the delta of map was less than mm hg (p= . ). this is probably due to an intraoperative disorders of the myogenic mechanism of blood flow autoregulation in the retinal microvasculature in patients with coronary artery disease [ ] . the level of map up to mm hg during cpb is associated with retinal blood flow impairment and the foci of ischemic retinal oedema. delta of map more than mmhg was associated with the foci of ischemic retinal oedema and decreased ganglionic fiber thickness in % of cases. atrial fibrillation after cardiac surgery: implementation of a prevention care bundle on intensive care unit improves adherence to current perioperative guidelines and reduces incidence introduction: atrial fibrillation after cardiac surgery (afacs) is a very frequent complication affecting - % of all patients. it is associated with an increase in morbidity, mortality and hospital and intensive care unit (icu) length of stay. we aimed to implement an afacs prevention care bundle based on a recently published practice advisory [ ] , focusing on early postoperative (re)introduction of β-blockers. baseline afacs incidence and β-blocker administration practices in our centre were audited for all patients undergoing valve surgery or coronary artery bypass graft (cabg) during a weeks period. the afacs prevention care bundlean easy to follow graphical toolwas subsequently introduced to the cardiac icu by a multidisciplinary team and audited following a model of improvement approach. after exclusion of patients with preoperative af, differences between pre-and post-implementation groups were compared with chisquare and fisher's exact tests for categorical, and one-way anova for continuous variables, using spss. a total of patients were analysed. patient and surgery characteristics did not differ between groups. significantly more patients received postoperative β-blockers after bundle implementation ( . % pre-vs . % post-bundle, p= . ) with a higher proportion on day ( . % pre-vs % post-bundle, p< . , figure ). the incidence of afacs was significantly reduced from . % to . % (p= . ), with a particularly marked reduction in the age group - years and for isolated aortic valve and cabg surgery. there was no significant reduction in hospital length of stay for this cohort. introduction of an afacs prevention care bundle using a graphical tool improved adherence to current guidelines with regards to early β-blocker administration and significantly reduced afacs incidence. future care bundles should include preoperative interventions and might reduce hospital length of stay. in neonates with univentricular physiology, there is a delicate balance between pulmonary and systemic circulations, with a tendency towards generous pulmonary blood flow, and a risk of systemic underperfusion. preoperatively, the use of hypoxic gas mixture (hm) has been advocated as a therapy to increase pvr, with the aim of improving systemic oxygen delivery. it is a therapy which has been routinely initiated in our institution in the setting of signs of pulmonary overcirculation. we performed a retrospective analysis of all patients in our institution who underwent a norwood procedure and who received hm preoperatively. we compared peripheral saturations, arterial blood gas analysis, serum lactate, regional cerebral and renal saturations and invasive blood pressure, prior to, and then , and hours after hm was commenced. between and (inclusive), patients underwent the norwood procedure. patients received preoperative hm. average fio was % during administration of hm. average peripheral saturations were . % prior to hm, and dropped to . % at hours, and % at and hours after initiation (p < . ). there was no change in any of the measured markers of systemic oxygen delivery, including regional cerebral and renal saturations, lactate, urine output or blood pressure. there was an association between an extended period of hm (> hours) and the need for pulmonary vasodilator therapy post norwood procedure. hypoxic gas mixture in patients with parallel systemic and pulmonary cicrculations causes desaturation and hypoxia. it does not lead to an increase in systemic perfusion and thus an improvement in systemic oxygen delivery. its ongoing use in this fragile population should be considered. introduction: analgesia in the critical patient, and especially in the neurocritical patient, is a basic goal in all therapeutic practices. patients in the icu are frequently administered prolonged and/or high doses of opioids. multiple serious complications due to the use of infusion of opioids at large doses has been described. to reduce high doses of intravenous opioids, multimodal forms of analgesia can be used. prospective observational study of the use of tapentadol enteral and buprenorphine in transdermal patches, at low doses, for the control of pain and its effect on reducing the use of fentanyl infusion in high doses on patients admitted to neuro icu of indisa clinic during consecutive years ( - ). enteral tapentadol (through ng tube) mg/ hours, was considered in patients who required intravenous fentanyl in continuous administration. buprenorphine was also added at low doses ( ug/hr) in a weekly transdermal patch, in cases of neurosurgical spine patients, fractures and long-term neuropathic pain. pain was controlled on behavioral pain scale (bps) and visual analogical scale (vas) scores, according to the conditions of each patient. their hemodynamic, gastrointestinal complications and the appearance of delirium episodes according to cam-icu scale were recorded. results: patients received tapentadol. of them also received transdermal buprenorphine. all managed to maintain adequate level of analgesia, not requiring fentanyl at doses greater than . ug / kg / hr. distribution by diagnoses: neurotrauma patients, guillain barre , spine surgery , hsa , hice , malignant ischemic acv . complications: gastric retention patients ( %), hypotension ( %), acute hypoactive delirium ( . %), acute hyperactive delirium ( %). no drug interactions were found. the introduction of enteral tapentadol and buprenorphine patches in neurocritical patients was safe and resulted in a decrease in the use of endovenous opioids and its adverse effects. we hypothesized that changing the pain management for our post cardiac surgical patients to an assessment-driven, protocol-based approach using fast acting and easily titratable agents will significantly improve patient satisfaction by reducing pain intensity in the first h after surgery as suggested by society of critical care [ ] guideline. we prospectively assessed and ( . vs . ) consecutive patients before and after introducing our pain management protocol. the nursing and medical team received rigorous training on the guideline as well as the correct assessment using appropriate pain scores measured at least hourly (numeric pain score, ≥ is timing of beta-blocker (re)initiation versus incidence of afacs before and after prevention care bundle implementation, per post-operative day and for postoperative days - (insets) moderate to severe or critical care observation tool, > is moderate to severe). we introduced a multimodal approach with a combination of fast acting iv, long acting oral opiates, regular paracetamol and rescue iv boluses for difficult to control situations and we created a prescription bundle on our electronic prescribing record. among other variables we assessed hours spent in moderate to severe pain in the first h after surgery and compared to the data collected before the guideline was introduced. we analysed patients from and from . baseline characteristics were similar between the two groups. in only . % of the patients spent less than hours and . % spend more than hours in moderate to severe pain. the data showed significant improvement in that . % of patients spent less than hours and only % patients who spent more than hours in moderate or severe pain. (p < . , chi square) ( figure ). only % of the patient needed rescue medications. % of time was the protocol inadequate necessitating other approach. introducing an assessment driven, stepwise, protocolized pain management significantly improved patient satisfaction by reducing pain intensity in the first h on our cardiothoracic intensive care unit. introduction: proximal femur fractures are most common fractures in the elderly and associated with significant mortality and morbidity, with high economic and social impact. perioperative pain management influence outcomes and mortality after surgery with early mobilization being possible [ , ] . the goal of the study was to compare the efficacy and safety of the compartment psoas block for perioperative analgesia in elderly patients with proximal femur fractures. the randomized controlled study was held in medical center "into-sana" (odesa, ukraine) from january till july . patients with proximal femur fractures and older than years were included in the study. they were randomly allocated to groupscompartment psoas block group (bupivacaine analgesia was started as soon as possible before surgery and prolonged during and after surgery with additional ischiadicus block before surgery) and general (inhalational) anesthesia with systemic analgesia perioperatively. results: patients were included in this study. perioperative compartment psoas block was associated better pain control, decreased opioid consumption, better sleep quality, earlier mobilization after surgery, decreased incidence of opioid-associated vomiting/nausea and myocardial injury. there were no difference in the incidence of hospital acquired pneumonia and delirium. perioperative compartment psoas block is effective and safe for perioperative analgesia in elderly patients with proximal femur fractures, and is associated with better pain control and decreased complications incidence. parenteral olanzapine is frequently used in combination with parenteral benzodiazepines for hospitalized patients with severe agitation. the fda issued a warning for increased risk of excessive sedation and cardiorespiratory depression with this combination based on post-marketing case reports with overall limited quality of evidence [ ] . the purpose of this study is to evaluate the safety and efficacy of concomitant parenteral olanzapine and benzodiazepine for agitation. this retrospective chart review evaluated agitated patients who received concomitant parenteral olanzapine and benzodiazepine within minutes from / / to / / . the primary end points were rate of respiratory depression requiring mechanical ventilation and hypotension requiring vasopressors. the secondary end points were percentage of patients requiring additional sedatives for agitation during the same time frame, cumulative dose of olanzapine and benzodiazepine (midazolam equivalent) received, and rate of cardiac arrest and death. a total of patients were included with notable baseline characteristics: median age of years old, % with a history of substance abuse, and % with a history of psychiatric illness. for the primary outcomes, . % of patients required mechanical ventilation and % required vasopressors. additionally, . % patients received additional sedating agents to control agitation. refer to table for more details. no cardiac arrests or deaths were observed. concomitant use of parenteral olanzapine and benzodiazepine within minutes for the treatment of agitation appears to have a small risk of respiratory depression without significant hypotension. hip fracture is very common in the elderly,it causes moderate to severe pain often undertreated. ficb is a simple safe method, easy to learn and use. the aim of our study is to assess the efficacy and safety of preoperative ficb compared with intravenous analgesia for elderly patients with femoral fracture and hip surgery in terms of opioid consumption and perioperative morbidity methods: after informed consent obtained, patients - yo asa i-iii with hip fracture were randomized to receive either an us guided ficb( ml of ropivacaine , %) or a sham injection with normal saline ' before surgery. both groups were operated under general anesthesia. postoperative analgesia was done according to vas: vas - mm, paracetamol g iv at h, vas - mm, ketoprofen mg iv at h, vas> , morphine , mg/ kgbw iv. the primary outcome was the comparison of vas score at rest over the first 'following the procedure, at the end of the surgery and at h intervals for h. the secondary outcome were the incidence of the cardiovascular events, of the ponv and of the confusion episodes, the amount of morphine consumption for h results: at baseline, ficb group (a) had a lower mean pain score than the sham injection group (b). the same difference was observed over h of follow-up (p< . ). there was a significant difference between the two groups in total cumulative iv morphine consumption at h and in the incidence of ponv and confusion episodes ( figure ). ficb provides effective analgesia for elderly patients suffering from hip fractures, with lower morbidity and lower opioid consumption compared with intravenous analgesia. pain assessment in chronic disorders of consciousness patients with ani monitoring e kondratyeva, m aybazova, n dryagina almazov national medical reseach centre, minimally conscious research group, st petersburg, russia critical care , (suppl ):p pain and suffering controversies in doc to be debated by the scientific, legal and medical ethics communities. methods: ani (anti nociception index) monitor was used to assess pain in patients with chronic disordersof consciousness (doc) age range to years - in vegetative state/ unresponsive wakefulness syndrome (vs/uws) and minimal consciousness state (mcs). average age: in mcs group , ± , and , ± , in vs/uws group. neurological status was assessed using crs-r scale. the average score on the crs-r scale was ± . in vs/uws and . ± . in mcs. pressure on the nail phalanx was used as a pain impulse. ani and nociception coma scale was evaluated before the application of pain stimulus, immediately after and past minutes. prolactin level was measured before the pain stimulus application and minutes after. ani less than indicates pain, - hypoalgesia, severe pain. the mean value of the ani in mcs patients: before the pain stimulus . ± . , after the pain stimulus application ± . and minutes later . ± . . prolactin level in mcs patients before pain . ± . ng/ml; after pain . ± . ng/ml (p> . ). prolactin in vs/uws patients before pain . ± . ng /ml, after pain . ± . ng / ml (p> . ). conclusions: ani monitor revealed that vs/uws and mcs patients react equally to the pain impulse. prolactin dynamics showed poor statistical mean and can not be consider as a marker of nociception in this group of patients. it is possible that the level of pain impulse was insufficient neuroendocrine response activation or the increase of prolactin level occurs in the long term (more than minutes). in all patients the total hip arthroplasty tha is one of the most common major surgical procedures associated with significant postoperative pain that can adversely affect patient recovery and could increase morbidity. effective perioperative pain management allows an accelerated rehabilitation and improve the functional status of these patients. multimodal analgesia mma combines analgesics with different mechanism of action which by synergistic and additive effects enhance postoperative pain management and reduce complications. the aim of our study is to assess if perioperative association of very low dose of ketamine, a potent nmda antagonist and dexamethasone, by antiemetic and antiinflammatory properties could decrease opioid consumption and postoperative morbidity of patients with tha. after informed consent, patients scheduled for primary hip joint replacement surgery aged - yo asa i-iii were prospective randomized in two groups. both groups were operated under general anesthesia fentanyl/sevoflurane. supplementary, patients in group a received mg iv dexamethasone and mg at h and ketamine mg iv bolus at induction and mg/h iv during surgery. postoperative analgesia was done according to vas, - mm paracetamol g iv at h, - mm ketoprofen mg iv at h, vas> mm morhine , mg/kgbw iv. we recorded perioperative opioid consumption, the number of intraoperative cardiac events, vas score at the end of surgery and at h, the incidence of ponv and persistance of chronic pain at months. we obtain a significant less pain score at the end of surgery p< . in group a, no significant difference at h, a significant less chronic pain at months, a fewer npvo and cardiovascular events in group a, p< . ( figure ). a multimodal approach with very low doses of ketamine and dexamethasone could be efficent in the treatment of pain for elderly patients with hip arthroplasty, decreasing postoperative side-effects and reducing chronic pain persistance. introduction: treatment in an intensive care unit (icu) often necessitates uncomfortable and painful procedures for patients. chronic pain is becoming increasingly recognized as a long term problem for patients following an icu admission [ ] . throughout their admission patients are often exposed to high levels of opioids, however there is limited information available regarding analgesic prescribing in the post-icu period. this study sought to examine the analgesic usage of icu survivors pre and post icu admission. methods: patients enrolled in a post-intensive care programme between september and june . intensive care syndrome: promoting independence and return to employment (ins:pire), is a -week multicentre, multidisciplinary rehabilitation programme for icu survivors and their caregivers. patients' level of analgesia was recorded pre-admission and upon attending ins:pire, their level of prescribed analgesia was categorized using the word health organisation (who) analgesic ladder [ ] . results: . % of patients (n= ) were prescribed regular analgesia preadmission; this increased to . % (n= ) post-admission, representing a significant absolute increase of . % ( % ci: . % - . %, p< . ) in the proportion of patients who were prescribed regular analgesia pre and post icu. in addition, pre-admission, . % (n= ) of patients were prescribed a regular opioid (step and of the who ladder) compared to . % (n= ) post-admission, representing an absolute increase of . % ( % ci: . % - . %, p< . ). this study found a significant increase in analgesic usage including opioids in icu survivors. follow-up of this patient group is essential to review analgesic prescribing and to ensure a long term plan for pain management is in place. introduction: pain, agitation, and delirium (pad) are commonly encountered b patients in the intensive care unit (icu). delirium is associated with adverse outcomes, including increased mortality and morbidity. clinical guidelines suggest that routine assessment, treatment and prevention of pad is essential to improving patient outcomes. despite the well-established improvements on patient outcomes, adherence to clinical guidelines is poor in community hospitals. the aim of this quality improvement project is to evaluate the impact of a multifaceted and multidisciplinary intervention on pad management in a canadian community icu. a pad advisory committee was formed and involved in the development and implementation of the intervention. the -week intervention targeted nurses (educational modules, visual reminders), family members (interviews, educational pamphlet, educational video), physicians (multidisciplinary round script), and the multidisciplinary team (poster). an uncontrolled, before-and-after study methodology was used. adherence to pad guidelines in the assessment of pad by nurses was measured weeks pre-intervention and weeks post-intervention. data on patient-days (pd) and pd were available for analysis during the pre-and post-intervention, respectively. the intervention significantly improved the proportion of pd with assessment of pain and agitation at least times per -hour shift from . % to . % and from . % to . %, respectively ( figure ). proportion of pd with delirium assessment at least once per -hour shift did not significantly improve. a multifaceted and multidisciplinary pad intervention is feasible and can improve adherence to pad assessment guidelines in community icus. quality improvement methods that involve front-line staff can be an effective way to engage staff with pad. oversedation introduction: sedation is a significant part of medical treatment in icu patients. a too deep sedation is associated with a longer time of mechanical ventilation, lung injury, infections, neuromuscular disease and delirium, which can lead to a longer duration of icu hospitalization, as well as an increase of morbility and mortality. many patients spend a considerable amount of time in a non-optimal sedation level. a continuous monitoring system of the sedation level is therefore necessary to improve clinical evaluation. our goal was to evaluate the incidence of non-optimal sedation (under and over sedation) comparing the parameters expressed from ngsedline with clinical evaluations and to correlate oversedation and the incidence of delirium. we have studied a cohort of patients admitted to the icu of spedali civili of brescia university hospital requiring continuous sedation for more than hours. in addition to standard monitoring, the patients have been studied using next generation sedline (masimo). sedation depth was evaluated through rass scale and the presence of delirium was evaluated with cam-icu scale. we collected data from adult patients. our data showed high incidence of oversedation. of our patients had a sr> and had a psi level< . a logistic regression analysis was performed and it showed statistically significant association between incidence of delirium and the age of the patients (p . ). the association between delirium incidence and suppression rate time was at the limits of statistics significance (p . ) and was statistically significant for non neurocritical patients (p . ). our study didn't show an association between delirium and the total time of sedation. non-optimal sedation is an unsolved problem in icu, affecting lot of patients, with a major incidence of over-sedation compared to under-sedation. our study shows an association between sr levels and the incidence of delirium. predictors of delirium after myocardial infarction, insights from a retrospective registry m jäckel, v zotzmann, t wengenmayer, d dürschmied, c von zur mühlen, p stachon, c bode, dl staudacher heart center freiburg university, department of cardiology and angiology i, freiburg, germany critical care , (suppl ):p delirium is a common complication on intensive care units. data on incidence and especially on predictors of delirium in patients after acute myocardial infarction (mi) are rare. by analyzing all patients after acute mi, we aim to identify incidence and potential risk factors for delirium. in this retrospective study, all patients hospitalized for acute mi treated with coronary angiography in an university hospital in were included and analyzed. incidence of delirium within the first days of care attributed to the mi and was defined by a nudesc score ≥ , which is taken as part of daily care three times a day by especially trained nurses. this research is authorized by ethics committee file number / . results: patients with acute mi (age . ± . years, stemi, mortality . %) were analyzed. delirium occurred in ( . %) patients and was associated with a longer hospital stay ( ± . d vs . ± . d, p< . ). patients with delirium were significantly older than patients without ( . ± . vs. . ± . years, p< . ) and had more often preexisting neurological diseases ( . % vs. . %, p< . ) and dementia ( . % vs. . %, p< , ). multivariate logistic regression analysis suggested that odds ratio for delirium was higher in patients after resuscitation or . ( % ci . - . ), preexisting dementia or . (ci . - ) and in patients with alcohol abuse or (ci . - ). while maximum lactate was also connected to delirium or . (ci . - . ), infarct size or type had no effect on the incidence of delirium. in patients with mi, delirium is frequent. incidence is associated with clinical instability and preexisting neurological diseases rather than infarct size. incidence and risk factors of delirium in surgical intensive care unit ma ali, b saleem aga khan university, anaesthesia, karachi, pakistan critical care , (suppl ):p introduction: delirium in the critically ill patients is common and distressing. the incidence of delirium in the icu ranges from % to %. although delirium is highly common among intensive care patients, it is mostly underreported. to date, there have been limited data available related to prevalence of delirium in surgical patients. in a study published in , the risk was observed % in surgical and trauma patients [ ] . the purpose of this study was to find out the incidence and associated risk factors of delirium in surgical icu (sicu) of a tertiary care hospital. we conducted prospective observational study in patients with age more than years and who were admitted to the surgical icu for more than hours in aga khan university hospital from january to december . patients who had preexisting cognitive dysfunction or admitted to icu for less than hours were excluded. delirium was assessed by intensive care delirium screening checklist icdsc. incidence of delirium was computed and univariate and multivariable analyses were performed to observe the relationship between outcome and associated factors. delirium was observed in of patients with an incidence rate of . %. multivariable analysis showed that copd, pain > and . ] were also the strongest independent predictors of delirium while analgesics exposures was not statistically significant to predict delirium in multivariable analysis. delirium is significant risk factor of poor outcome in surgical intensive care unit. . there was an independent association between pain, sedation, copd, hypernatremia and fever in developing delirium delirium is an acute mental syndrome which may cause negative consequences if it is misdiagnosed [ , ] . the aim of this study was to determine the incidence of delirium in different intensive care units and reveal the risk factors. the study was performed with patients hospitalized in intensive care units of anesthesia, neurology and general surgery departments. written informed consent was obstained from patients or relatives. delirium screening test was performed twice daily with camicu (confusion assessment method for the icu). patients who met the study criterias, were evaluated for the possible risk factors of delirium and the data was recorded daily. patients were reevaluated after the treatment. the incidence of delirium was . %. delirium was found to increase with the length of stay (p < . ). the mean age of the patients with delirium was . . this was higher than the patients without delirium ( . ) (p< . ). visual impairment (p< . ), hearing impairment (p= . ), educational status (p= . ), hypertension (p= . ), mechanical ventilation (p = . ), oxygen demand (p= . ), midazolam infusion (p= . ), propofol infusion (p= . ), infection (p < . ), sofa (p = . ), apache ii (p < . ), nasogastric catheter (p= . ), aspiration (p < . ), number of aspirations (p< . ), enteral nutrition (p< . ), albumin (p= . ), steroid (p= . ), hypercarbia (p= . ) hypoxia (p= . ), sleep disturbance (p< . ) were found risk factors for delirium. oral nutrition (p< . ) and mobilization (p= . ) were found to prevent delirium development. various factors are important in the development of delirium. these risk factors should be considered in reducing the incidence of delirium in intensive care units. ). an unplanned and brutal stop of alcohol consumption, as it can occur during icu admission, may lead to an alcohol withdrawal syndrome (aws). the most severe clinical manifestation of aws is described as delirium tremens (dt). there are no current guidelines available for aws treatment in icu. the study's aim was to describe the clinician's practices for dt treatment and the outcome of dt in icu patients. observational retrospective cohort study in two icus of a universityaffiliated, community hospital in france. patient diagnosed for dt during their icu stay, as defined by dsm-v classification, were enrolled in the study. results: patients with dt were included between and . benzodiazepines was administered to % of the patients in order to prevent an aws. as associated measures, vitamin therapy was administered to % of the patients and % had an increased fluid intake (mean . l+/- . ). concerning the curative approach of aws, the treatment's heterogeneity was notable. there was a high frequency of treatment's association ( % of the patients), every patient had benzodiazepines and the use of second line treatments such as neuroleptic, alpha- agonist, propofol was variable ( figure ). complications of dt were the following: need for mechanical ventilation due to unmanageable agitation or acute respiratory distress ( % of the patients) self inflicted injuries such as pulling out of central lines, tubes, surgical drain ( %) falls ( %). seizures ( %). delirium tremens is a severe complication of an untreated aws, which can lead to serious adverse events in icu. the current lack of evidence concerning the management of aws in icu probably explains the heterogeneity of treatments. given the potential severity of aws in icu, further evidences are required to optimize care of aws in icu patients. the incidence and related risk factor of delirium in surgical stepdown unit s yoon , s yang , g cho , h park , k park , j ok , y jung asan medical center, nursing department, seoul, south korea; asan medical center, seoul, south korea critical care , (suppl ):p step down units (sdus) provide an intermediate level of care between the icu and the general medical-surgical wards. the critically ill patients who are in recovery after long-term intensive care or who require monitoring after acute abdominal surgery are admitted to sdus. delirium in critically ill patient is common and leads to poor clinical outcomes. it is, however, preventable if its risk factors are identified and modified accordingly. to determine risk factors associated with delirium in critically ill patients to admitted surgical sdu at asan medical center. this is retrospective study conducted on critically ill patients who were admitted to the sdu from september to april and able to express themselves verbally. delirium status was determined using the short-cam tool. data were analyzed by spss . software, using t-test, fisher's exact test and logistic regression. the incidence of delirium was . %( of patients) and hypoactive delirium( case, . %) was the most commonly assessed, followed by hyperactive delirium( case, . %), mixed type( case, . %). risk factors associated with developing delirium identified from univariate analysis were age(p= . ), admission via icu (p= . ), tracheostomy (p= . ), chronic heart failure (chf) (p= . ), invasive hemodynamic monitoring (p= . ), heart rate (p= . ). after adjusted in multivariate analysis; factors those remained statistically significant were old age (rr we identified risk factors consistently associated with incidence of delirium following admitted to surgical sdu. these factors help to focus on patients at risk of developing delirium, and to develop preventive interventions that are suitable for those patients. patients with sepsis frequently develop delirium during their intensive care unit (icu) stay, which is associated with increased morbidity and mortality. the prediction model for delirium in icu patients (pre-deliric model) was developed to facilitate the effective preventive strategy of delirium [ ] . however, the pre-deliric model has not yet been validated enough outside europe and australia. the aim of this study is to examine the external validity of the pre-deliric model to predict delirium using japanese cohort. this study is a post hoc subanalysis using the dataset from previous study in nine japanese icus, which have evaluated the sedative strategy with and without dexmedetomidine in adult mechanically ventilated patients with sepsis [ ] . these patients were assessed daily throughout icu stay using confusion assessment method-icu. we excluded patients who were delirious at the first day of icu, were under sustained coma throughout icu stay and stayed icu less than h. we evaluated the predictive ability of the pre-deliric model to measure the area under the operating characteristic curve. calibration was assessed graphically. of the patients enrolled in the original study, we analyzed patients in this study. the mean age was . ± . years and patients ( %) were male. delirium occurred at least once during their icu stay in patients ( %). to predict delirium, the area under the receiver operating characteristics curve of the pre-deliric model was . ( . to . ). graphically, the prediction model was not well-calibrated ( figure ). to predict delirium in japanese icus, we could not show the well discrimination and calibration of the pre-deliric model in mechanically ventilated patients with sepsis. introduction: delirium is a serious and common complication and in some cases it treatment is difficult. aim of the study was an evaluation of the prevalence, structure of delirium and efficacy of dexmedetomidine and haloperidol sedation in geriatric patients after femur fracture. after local ethic committee approval case-records of geriatric patients with femur fracture in the period from to in the institute of traumatology and orthopedics in astana were analyzed. patients was divided for groups: in dpatients with delirium treated by i/v dexmedetomidine ( . - . mkg/kg per hour), in g group patients with delirium treated by i/v galoperidol ( . - . mkg/kg). delirium was assessed by rass at day of permission and every day at a.m. the prevalence, structure of delirium and efficacy of sedation were analysed. results: by anthropometric and gender characteristics of the group did not differ. the average age in the d-group with delirium was . ± . years old, which was comparable to the g-group - . ± . years old (p = . ). all study participants had similar comorbidities. delirium in all patients debuted at . ± . days, with an average duration of . ± . days. the effect of dexmedetomidine was better and expressed in % decrease in the duration of delirium in compare to haloperidol (p < . ). dexmedetomidine provided a more controlled and safe sedation compared with haloperidol. the average consumption of narcotic analgesics in the subgroup with dexmedetomidine was two times less than in the subgroup with haloperidol. thus, the average consumption of trimeperidine hydrochloride in patients of group d was . mg versus . mg in group g (p = . ). in gerontological patients with femur fracture treatment delirium by dexmedetomidine was more effective in compare with haloperidol. when using dexmedetomidine, the consumption of narcotic analgesics in postoperative period was % less than with haloperidol. live music therapy in intensive care unit mc soccorsi , c tiberi , g melegari , j maccieri , f pellegrini , e guerra intensive care units (icu) are not comfortable for patients, relatives or next of kin. in the last years many news approaches were described to implement the humanization of medical treatments. the positive effect of music therapy in icu is well described, especially reducing delirium risk [ ] . the aim of this paper is describing the effect in patients and their family of a music live performance in icu. after ethical committee approval (procedure aou / , italy) for three months (november -january ) patients in icu were treated twice a week with live music therapy performed by coral vecchi-tonelli of modena, italy (fig. ). data were collected all awake and conscious patients. vitals parameters, gcs, raas and cam icu were collected before, during and after the treatment, at every performance. after the treatment a feedback questionnaire were given to patients and to next of kin. results: subjects were enrolled in the research with mean age of . years old, delirium rate before the treatment was . % later . %, raas does not show any difference. over % of patients were satisfied, and relatives felt less anxiety. we recorded also a satisfaction also in relatives not enrolled. the study does not demonstrate a delirium risk reduction for the small sample and the length treatment, anyway it was recorded a low delirium rate. the safety and the potential effect of music therapy are well known, surely the research underlines the feeling of patients and their next of kin: icu is the most stressful setting for admitted patients and its humanization is a current topic for medical literature. live performances could be an entertainment moment and probably create a moment of an interaction among patients, their family and medical and nurse: icu become more human. the high level of satisfaction push us to continue this experience. introduction: patients undergoing medical procedures benefit from distraction techniques to reduce the need for drugs alleviating pain and anxiety. this study investigates if medical hypnosis or virtual reality glasses (vrglasses) as adjuvant method reduces the need for additional drugs. in a prospective, randomized, interventional trial, patients undergoing procedures were stratified in four age groups, and randomly assigned into three arms by means of a closed envelope system. all patients received standard care for pain before the procedure; the control group received further drugs for pain and stress as indicated by the visual analog scale (vas; threshold / ) and comfortscore (threshold / ), two index groups received either medical hypnosis or vr glasses as a plus before and during the procedure. vas and comfort were scored continuously and analysed with the kruskal-wallis test. patients, parents and healthcare providers scored their satisfaction at the end. of included patients to years old, % were female. regardless of age, pain and comfort scores were similar before and at the start of the procedure (vas . - . ; comfort - . ), but as of one minute after starting the procedure, both vas and comfort reduced significantly more in both index groups compared to the control (p< . ), remaining far below the threshold for both pain and stress ( figure ). there was no advantage of one index group over the other (p= . ). there were no adverse effects. patients in the vr group were more satisfied than in the standard group (p= . ) or in the hypnosis group (p= . ). there was no significant difference in satisfaction of parents or healthcare providers. from the very start of the intervention, the application of either medical hypnosis or vr glasses significantly reduces pain and anxiety in patients undergoing medical procedures. more studies are needed but both are promising safe adjuvant tools to standard pharmacological treatment. music to reduce pain and distress due to emergency care: a randomized clinical trial ne nouira, i boussaid, d chtourou, s sfaxi, w bahria, d hamdi, m boussen, m ben cheikh mongi slim academic hospital, emergency department, tunis, tunisia critical care , (suppl ):p recent clinical studies have confirmed the benefits of music therapy in managing pain and improving quality of care in the emergency department. the aim wasto evaluate the impact of receptive music therapy on pain and anxiety induced by emergency care methods: a randomized controlled study in patients consulting the emergency department. two groups: the music therapy group; patients needed venous sampling, peripheral venous catheter or arterial catheter. will bless ten minutes music therapy by headphones and a second control group of patients with the same care without music therapy. consent was requested from all participants. the level of pain caused by the act of care was assessed by visual analogic scale. heart rate, blood pressure and the mood of the patient were assessed before and after emergency care. we assessed patient satisfaction, adverse events. patients admitted to the emergency room, patients with communication difficulties and non-consenting patients were not included results: two hundred and forty patients were included randomized in both groups, with music therapy and without music therapy, the results showed comparable characteristics between the two groups: demographic data, pathological history, and initial clinical presentation. after the session of music therapy a difference was noted in the evaluation of the mean vas who was in the group with music of . ± . versus . ± . in the control group p< . ci % [- . ; - . ], and the mean of diastolic blood pressure which was , mmhg in the first group against . mmhg for the control group p = . ci % [- . ; - . ]. as for the mood, the patients were more smiling after the act of care in the group music therapy. all patients were satisfied with their experience and % recommend this therapy to their relatives . music therapy may reduce pain and anxiety in patients during emergency care. the music therapy is the intervention of music and/or its elements to achieve individual goals within a therapeutic.the music has proved to have positive physiological and psychological effects on patients [ ] . patients admitted to the intensive care unit (icu) experience anxiety and stress even when sedated, negatively influencing recovery [ ] . methods: two groups are established, a music therapy group (mg) and a control group (cg). the first one undergoes music therapy interventions, it consists of -minutes sessions of live music. patients of the gc will receive the usual treatment established by the service protocol for weaning management and the data are collected during the same time interval. data collection includes mean arterial pressure (map), heart rate (hr), respiratory rate (rr), oxygen saturation (sao ) and temperature (t). a total of patients were recruited, of which patients had to be excluded for meeting any of the exclusion criteria (n= ). of which (n= ) were randomized in the gm and the rest to the gc (n= ) ic %. regarding delirium in gm ( . %) presented a positive cam-icu, while in the cg were ( . %) (p= . ). when analyzing the variables in the cg and gm, it was observed that there were no differences with respect to hr, rr and map variable ( figure ). according to the results, we can say that music therapy as a nonpharmacological strategy for management of anxiety and delirium in patients of critical care units, might be an useful tool for the management of patients in weaning of mechanical ventilation introduction: coagulopathy and basopenia are common features of anaphylaxis, but the role of coagulopathy in anaphylaxis remains uncertain. the aim of this study is to evaluate the association between coagulopathy and clinical severity or basopenia in patients with anaphylaxis. we conducted a single-center, retrospective study of patients with anaphylaxis about their coagulopathy. levels of fibrin degradation products (fdp) and d-dimer were analyzed with the cause of anaphylaxis, clinical symptoms, medications and outcomes. we also studied the levels of intracellular histamine as a biomarker of basophil degranulation in the peripheral blood in relation to fdp and ddimer. in total, sixty-nine patients were enrolled to the study, and the levels of intracellular histamine were analyzed in patients. the symptoms included respiratory failure (n= ), shock (n= ), abdominal impairment (n= ), and consciousness disturbance (n= ). thirty-two patients needed continuous intravenous vasopressors for refractory shock. the increase of fdp was significantly associated with consciousness disturbance (p= . ) and refractory shock (p< . ). the increase of d-dimer was also significantly associated with refractory shock (p= . ). there was no correlation between the levels of intracellular histamine and either of fdp or d-dimer (p= . and p= . , respectively). the increase of fdp and d-dimer were associated with severe symptoms of anaphylaxis, while they were not correlated with intracellular histamine. these results suggest that anaphylaxis is closely associated with coagulopathy in a mechanism which is different from basophile degranulation in anaphylaxis. cardiac manifestations of h n infection in a greek icu population e nanou , p vasiliou , e tsigou , v psallida , e boutzouka , v zidianakis , g fildissis agioi anargiroi hospital, attiki, greece; agioi anargiroi hospital, icu, attiki, greece critical care , (suppl ):p introduction: cardiovascular involvement in influenza infection occurs through direct effects on the myocardium or through exacerbation of pre-existing cardiovascular disease [ ] . the aim was to study cardiac manifestations in all pts admitted to the icu with severe influenza's attack. clinical, laboratory, electrocardiographic, echocardiographic and hemodynamic data were retrospectively recorded in all pts admitted to the icu due to influenza infection (winter -spring ). diagnosis was established by pcr on bronchial aspirates the next days after admission. myocardial injury was defined by troponin levels > pg/ml ( fold uln). left ventricular systolic dysfunction was defined as ef < % and was characterized as either global or regional. hemodynamic monitoring by fig. (abstract p ) . comparison between mg and cg transpulmonary thermodilution method (picco) was recorded in pts with shock (norepinephrine > . μg/kg/min). values are expressed as mean±sd or as median (ir). results: nine pts ( males) with a mean age . ± . years, apache ii ± . and sofa score . ± . were assessed. icu admission was due to ards ( ) and copd exacerbation ( ) . icu los was . ± . days and mortality rate was %. no history of vaccination or coronary heart disease was referred. results are shown in table . levosimendan was administered in pts with severe cardiogenic shock. in all survivors, shock and indices of myocardial dysfunction subsided till discharge. coronary angiography was performed in pt showing no abnormalities. mortality was attributed to septic shock and multi-organ failure. myocardial involvement, though common in influenza pts admitted to the icu, didn't contribute to a dismal prognosis. the cardioprotective effects of levosimendan could be related to the modulation of oxidative balance. we aimed to examine the effects of levosimendan in patients with cardiogenic shock or with ejection fraction (ef) lower than % on cardiac systo-diastolic function and plasma oxidants/antioxidants (glutathione, gsh; thiobarbituric acid reactive substances, tbars). in patients undergone coronary artery bypass grafting or angioplasty, cardiovascular parameters were measured at t (before the beginning of levosimendan, . mcg/kg/min), t ( h after the achievement of the therapeutic dosage of levosimendan), t (at the end of levosimendan infusion), t (at h after the end of levosimendan infusion), t (at the end of cardiogenic shock). the same time-course was followed for plasma gsh and tbars measurements. we found an improvement in cardiac output, cardiac index and systolic arterial blood pressure. ef increased from mean % to %. a reduction of central venous pressure and wedge pressure was also observed. moreover, indices of diastolic function were improved by levosimendan administration (e/e' from to ; e/a from > to < ) at early t . it is to note that an improvement of gsh and tbars was observed early after levosimendan administration (t ), as well ( figure ). the results obtained have shown that levosimendan administration can regulate oxidant/antioxidant balance as an early effect in low cardiac output patients. the modulation of oxidative condition could be speculated to play a role in exerting the cardio-protection exerted by levosimendan in those patients. table . early administration of vasopressors and their use in the emergency department was associated with survival in septic shock. this seemed to be independent of median map recorded in the ed. we excluded all the traumatic or post-myocardial infarction forms. out of patients, the tuberculous etiology was identified in cases ( , %), mean age was years, , % were men. patients reported a tb contact in their environment, had a medical history of pulmonary tb. after pericardiocentesis, the liquid was citrine yellow in cases and hematic in patients, no patient underwent surgical drainage in our serie. mycobacterium tuberculosis was found in the expectorations in cases and ada was positive in patients. hiv serology was negative in all our patients. a months anti bacillary therapy with isoniazid, rifampin, pyrazinamide, and ethambutol was initiated in all our patients with a good evolution in cases, deaths, chronic constrictive pericarditis, small pericardial effusion and lost to follow-up. althought cardiac tamponade is rarely caused by tuberculosis, this condition remains common in endemic countries such as morocco and affect younger population, hence the importance of a better knowledge of its prevalence and and multidisciplinary management and more importantly the treatment of the underlying cause using combined antibacillary medication that has shown satisfying results. . the main perceived limiting factor is the absence of a standardized didactic program, followed by mentor's availability in residents' perception and by mentor's experience in consultants' one. pocus teaching is present although not optimal and not homogenous in italian acc residency schools. standardisation of residents' ultrasound curriculum is suggested to improve ultrasound teaching. the study included a convenience sample of critically ill patients with supradiaphragmatic cvcs and a cxr for confirmation. us is used for direct confirmation of the guidewire in the internal jugular (ijv) or subclavian (scv) vein and visualizing the guidewire in the right atrium. to evaluate for pneumothorax, "sliding sign" of the pleura was noted on us of the anterior chest. results: patients have been included, % of the catheters have been placed in the scv and % in the ijv. it was possible to confirm the position of the cvc tip for . % ( correct, incorrect cxr) of (figure ). overall, it was not possible to identify the guide in the right atrium cases ( false negatives, of them due to the presence of defibrillator leads). regarding the case where an incorrect position was seen on cxr it was also detected on ultrasound: us of the inserted vein and a negative tte confirmation. in all cases it was possible to exclude a pneumothorax by us. these results show that bedside ultrasound might be a feasible technique to confirm the cvc positioning. it is important to note that the level of the operator's expertise is significant when assessing the feasibility of this method. we only had a limited sample size and the occurrence of only one misplaced catheter. these preliminary results need to be confirmed on a larger scale. central venous catheter (cvc) misplacement occurs more frequently after cannulation of the right subclavian vein compared to the other sites for central venous access. misplacement can be avoided with ultrasound guidance by using the right supraclavicular fossa view to confirm correct guidewire j-tip position in the lower part of the superior vena cava. however, retraction of the guidewire prior to the cvc insertion may dislocate the j-tip from its desired position, thereby increasing the risk of cvc misplacement. the aim of this study was to determine the minimal guidewire length needed to maintain correct guidewire j-tip position throughout an us-guided infraclavicular cvc placement in the right subclavian vein. methods: adult intensive care patients with a computed tomography scan of the chest were retrospectively and consecutively included in the study. the distance from the most plausible distal puncture site of the right subclavian/axillary vein to the junction of the right and left brachiocephalic veins (= vessel length) was measured using multiplanar reconstructions. in addition, measurements of the equipment provided in commonly used - cm cvc kits were performed. the minimal guidewire length was calculated for each cvc kit. the guidewires were up to mm too short to maintain correct j-tip position throughout the cvc insertion procedure in seven of nine commercial cvc kits. four of these are shown in table . when us guidance is used to confirm a correct guidewire j-tip position, retraction of the guidewire prior to the cvc insertion must be avoided to ensure correct cvc-tip positioning. this study shows that most of the commonly used - cm cvc kits contain guidewires that are too short for cvc placement in the right subclavian vein. the reliability of lung b-lines to assess fluid status in patients with long period of supine introduction: ultrasound-guided cannulation is usually done using either longitudinal or transverse approach. the oblique approach utilizes advantages of both these approaches allowing visualization of the entire course of needle including tip and lateral discrimination of artery from vein [ ] . the reported incidence of the complete overlap of femoral vein by the femoral artery is - percent [ , ] . we describe the use of the oblique approach for successful cannulation of such a femoral vein which is not possible by usual approaches (figure ). endothelial cells play a pivotal role in the atherogenic process. endothelial cell dysfunction (ed) is the main risk factor for cardiovascular diseases such as hypertension, coronary heart disease (chd) and peripheral occlusive disease (pod). these diseases significantly increase the risk for perioperative complications. therefore, identifying patients with ed is important and should influence our prospective perioperative strategy. however, sensitive tools to diagnose ed are still missing and do not belong to our standard of care. aim of this study was the validation of a new non-invasive method to detect ed and a correlation with a set of established an new endothelial biomarkers. the cohort includes preoperative patients without anamnestic relevant cardiovascular disease and patients with known peripheral occlusive disease (pod). we used non-invasive endopat® technology from itamar-medical to measure ed by changes in vascular tone before and after occlusion of the brachial artery and calculate a reactive hyperemia index (rhi). in addition, we measured established markers and alternative biomarkers potentially indicate vascular diseases such as substrates and products from the no-metabolism l-arginin, asymmetric/symmetric dimethylarginine (adma/sdma), von-willebrand factor (vwf) and sphingosine- -phosphate (s p). rhi was able to identify patients with pod. rhi was significant lower in patients with clinical signs and symptoms of pod (p< . ). among other markers adma was significant higher in pod patients compared to controls and correlates with rhi. the pad technology is a helpful non-invasive functional test to measure ed and seems able in identify patients with vascular disease. in future, a combination of anamnesis, new diagnostic tools and biomarkers may further increase our sensitivity in identifying risk-patients. single-lumen fr and triple-lumen fr peripherally inserted central catheters (piccs) for cardiac output assessment by transpulmonary thermodilution s d´arrigo achieving effective critical care in low-and middle-income countries is a global health goal [ ] , which includes the provision of effective point of care ultrasound [ ] . we sought to establish zambia's first focused critical care echocardiography training programme in a bedded icu at university teaching hospital, lusaka. the programme was accredited by the uk intensive care society fice programme, with teaching adapted for local disease patterns such as tuberculous pericardial effusions. parasternal, apical and subcostal windows were used to assess ventricular dysfunction, hypovolaemia, pleural effusion, alveolar interstitial syndrome and pneumothorax. zambian doctors working with critically ill patients received an intensive one-day course, followed by mentored scanning at the bedside. teaching was delivered by visiting fellows from the uk who are accredited in echocardiography and experienced ultrasound educators. patients with abnormal mean ci or hr suffer from increased hospital mortality. abnormality of mean svi was not associated with mortality. these data support accurate measurement of ci as a hemodynamic target and the normal range defined for ci. since ci also carries the hr information, ci seems to be the more important target than svi. our data cannot necessarily be interpolated to less invasive and less precise measurements of ci. an evaluative study of the novelty device with the function of auto-aspirating and pressure indicator for safety central venous catheterization ly lin, wf luo, cy tsao national taiwan university hospital, taipei, taiwan critical care , (suppl ):p previous studies have shown that . % of cvc attempts resulted in arterial punctures that were not recognized by blood color. to overcome the problem, our team has developed a concept of pressure detecting syringe that can indicate the artery puncture [ ] . based on previous research, different springs, the actuator of the design, have been evaluated to optimize the proposed device and reduce the risk of cvc procedure. tested devices -the inner-spring is set between the pressure indicator and plunger (fig. a ). three springs are tested. test condition -blood samples were simulated by glucose solution with absolute viscosities of and mpa-s. different blood pressures were applied to simulate the artery and vein (fig. b) . the response time (rt) is defined as the time required to show the indicating signal (is) which is the movement of the piston from the position in fig. b : a - to a - . the rt is strongly influenced by spring (fig. b) but every design can show the is when pressure is higher than mmhg, the assumed minimum artery pressure. the rt of s , the strongest spring design, is about s in the mmhg-pressure and high viscosity condition. during our tests we found the user can realize the is before the position be fully changed from fig. ib : a - to a - . thus, we believe the s rt, the worst case, is still acceptable. we also found the weak spring force may lead to difficulty to empty the syringe because the spring must to overcome the blood pressure and the friction between the piston and barrel. as a result, it was difficult for s to absolutely empty the syringe even if the blood pressure is only mmhg. the spring will be compressed as fig. b : a - and fail to push the piston when pushing the plunger forwardly, which is not acceptable in clinical use. the results indicate the feasibility of using the device to facilitate cvc and we believe the s or s are more suitable for the future application. introduction: models using standard statistical features of hemodynamic vital sign waveforms (vs) enable rapid detection of covert hemorrhage at a predetermined bleed rate [ ] . by featurizing interactions between vs we can train powerful hemorrhage detectors robust to unknown bleed rates. waveforms (arterial, central venous, pulmonary arterial pressures; peripheral and mixed venous oxygen saturation; photoplethysmograph; ecg) of healthy pigs were monitored min prior and during a controlled hemorrhage at ml/min (n= ) and ml/min (n= ). two sets of vs features were extracted: statistical features [ ] and maximal pairwise cross correlations between pairs of vs within a s lag over various time window sizes ( s, s, s, s); and normalized with pre-bleed data of each given animal. for each feature set, a tree-based (ert) model [ ] was trained and tested in a one-animal-out setting to mitigate overfitting on the ml/min cohort, and another trained on the ml/min and tested on the ml/min cohort. we evaluated models with activity monitoring operating characteristics curves [ ] that measure false alert rate as a function of time to detect bleeding. models using cross-correlations show no significant deterioration of performance when applied to detect bleeding at different rates than trained for, while standard models require s longer on average to detect hemorrhage at % false alert rate in the previously unknown setting ( figure ). correlations between vs data encode physiologic responses to hemorrhage in a way independent of the actual bleed rates. this enables training effective hemorrhage detectors using only limited experimental data, and using them in practice to detect bleeding that occurs at rates other than used in training. we validated a dataset of data lines containing hemodynamic variables and treatment options. we selected nine hemodynamic variables as inputs. furthermore, data were collected regarding underlying conditions: heart failure, septic shock, renal failure or respiratory failure or a combination. we applied datastories regression on the dataset (turnhout, belgium, www.datastories.com). six different interventions were analyzed as kpi: administration or removal of fluids, increasing or decreasing inotropes and increasing or decreasing vasopressors. finally, we elaborated and challenged predictive models to generate a decision algorithm to predict each kpi. we first looked at how each hemodynamic parameter impacts the prediction of each kpi individually and performed a standard correlation analysis as well as a more involved analysis of the mutual information content between each kpi and all other hemodynamic parameters individually. confusion matrix and variable importance was obtained for each kpi. the baseline hemodynamic parameters were: gedvi ± ml/m , evwli . ± . ml/kg pbw, svv . ± %, mbp . ± . mmhg, hr . ± . bpm, ci . ± . l/min.m . the results of the regression analysis identified the different variables of importance for each of the different interventions ( fig a) . based on these results the hemodynamic variables (hr, mbp, gedvi, elwi, ci, svv) were used to develop the final hemoguide prediction model ( fig b) . the hemoguide app can be used to advise physicians with respect to basic therapeutic decisions at the bedside or as an educational tool for students. with the collection of new data, the accuracy of the system may grow over time. the next step of the project is to develop a more-sophisticated suite: the icu cockpit. feedback function contributes to accurate measurement of capillary refill time r kawaguchi , ta nakada , m shinozaki , t nakaguchi , h haneishi , s oda chiba university, department of emergency and critical care medicine, chiba, japan; chiba university, chiba, japan critical care , (suppl ):p capillary refill time (crt) is well known as an indicator of peripheral perfusion. however, it has been reported to have an intra-observer variance, partly because of manual compression and naked-eye measurement of the nailbed color change. we hypothesized that a we developed a novel portable crt measurement device with an oled display that feedbacks weather the strength of the nailbed compression is enough and counts the time. we settled the target strength and time as n and seconds according to the study we reported before [ ] . examiners measured crt with and without the feedback function. the pressing strength and time during the measurement were evaluated. there was a significant difference among the pressing strength and time between the crt measurement using the device with and without the feedback function (strength: p< . ; time: p< . ). furthermore, intra-examiner variance was significantly reduced with the feedback function (strength: p< . ; time: p< . ). in all measurements without the feedback function, % was outside the optimal strength while the measurements with the feedback function % achieved the targeted range. without the feedback function, % could not reach the optimal time, while % with the feedback function did. in total, % of the measurements could not achieve the optimal pressing strength and time. the feedback function for crt measurements, guiding examiners to an optimal pressing strength and time, fulfilled the required measurement conditions and reduced intra-examiner variance. our novel portable device would assist an accurate crt measurement regardless of personal work experience. introduction: the aim of the study was to detect the difference of conjunctival microcirculation between septic patients and healthy subjects and evaluate the course of conjunctival microcirculatory changes in survivors and non-survivors over a hours period of time. this single-centre prospective observational study was performed in mixed icu in a tertiary teaching hospital. we included patients with sepsis or septic shock within the first hours after icu admission. conjunctival imaging using idf videomicroscope as well as systemic hemodynamic measurements were performed at three time points: at baseline, hours and hours later. baseline conjunctival microcirculatory parameters were compared with healthy control. a total of patients were included in the final assessment and analysis. median apache ii and sofa scores were ( - ) and ( - ) respectively. ( %) were in septic shock, ( %) required mechanical ventilation. patients were discharged alive from the intensive care unit. we found significant reductions in all microcirculatory parameters in the conjunctiva when comparing septic and healthy subjects. we found a significant lower proportion of perfused vessels and microvascular flow index (mfi) of small vessels during all three time points in non-survivors compared with survivors. in nonsurvivors we observed no significant changes in conjunctival microcirculatory parameters over time. however, survivors had significantly improved mfi of small vessels at second and third time points compared to first time point. microcirculatory perfusion in conjunctiva was altered in septic patients. over hours evaluation survivors in comparison with nonsurvivors had better microcirculatory flow with incremental improvement of microvascular flow index. healthy pigs were centrally cannulated for veno-arterial ecmo and precision flow probes were placed on the pulmonary artery main trunk for reference. ml boluses of iced . % saline chloride solution were injected into the ecmo circuit and right atrium at different ecmo flow settings ( , , , l/min). rapid response thermistors of standard pa-catheters in the ecmo circuit and pulmonary artery recorded the temperature change. after calibration of the catheter constants for different injection volumes in the ecmo circuit, the distribution of injection volumes passing each circuit was assessed and enabled calculation of pulmonary blood flow. analysis of the exponential decay of the signals allowed assessment of right ventricular function. calculated blood flow correlated well with true blood flow (r = . , p < . , figure panel a, individual measurements organ congestion is susceptible to be a mediator of adverse outcomes in critically ill patients. point-of-care ultrasound (pocus) is widely available and could enable clinicians to detect signs of venous congestion at the bedside. the aim of this study was to develop prototypes of congestion scores and to determine their respective ability to predict acute kidney injury (aki) after cardiac surgery. this is a post-hoc analysis of a prospective study in patients for which repeated daily measurements of hepatic, portal, intra-renal vein doppler and inferior vena cava (ivc) ultrasound were performed before surgery and during the first hours after cardiac surgery [ ] . five prototypes of venous excess ultrasound (vexus) scores combining multiple ultrasound markers were developed (figure ). the association between each score and aki was assessed using timedependant cox models as well as conventional performance measures of diagnostic testing. a total of ultrasound assessments were analyzed. we found that defining severe congestion as the presence of severe flow abnormalities in multiple doppler patterns with a dilated ivc (> cm), corresponding to grade of the vexus c score, showed the strongest association with the development of subsequent aki compared with other combinations of ultrasonographic features (hr: . there is an increasing awareness on the consequences of fluid administration in patients leading to the development of methods that evaluate the effects of fluids loading on the cardiocirculatory system. however, most of methods used in the clinical practice investigate the effects of fluids on the cardiac function, instead of investigating those on the determinants of venous return. besides volume of fluids, the determinants of fluid loading are the blood volume distribution and the availability of vascular bed. in this study we aimed to test non-invasively the effects of fluids administration on the venular compartment in the skeletal muscle. in addition to the mean systemic filling pressure (msfp), we calculated changes in the stressed and unstressed volumes (vs, vu) and the venular bed availability. we enrolled critically ill patients in our intensive care unit. we assessed volumes and pressures by the near infra-red spectroscopy on the forearm using graded venous occlusions in steps of mmhg from to mmhg. the msfp, vu and vs were measured as previously reported (microcirculation ; : - ). the vascular bed availability was measured by changes in the volume recruited from the occlusion maneuvers. all the measures were done at baseline and after a fluid load ranging from to ml. values were expressed as median and interquartile range. wilcoxon test was used to compare data and a p< . was considered as significant. introduction: hypotension is a common side effect of general anesthesia (ga) and is associated with organ hypoperfusion and poor perioperative outcome [ ] . post-induction hypotension (pih) is caused by the depressant cardiovascular effect of anesthetic drugs and could be amplified by hypovolemia. the aim of this study was to assess the ability of two echocardiographic fluid responsiveness markers to predict pih: the inferior vena cava collapsibility index (ivc-ci) and the velocity time integral change (Δvti) after passive leg raising. sixty patients > years of age and scheduled for elective surgery were included. ivc-ci and Δvti were measured before ga induction. anesthesia protocol, fluid infusion and vasopressor administration were standardized in all patients. pih was defined as a mean arterial pressure (map) < mmhg or a relative decline from pre-induction value of at least % within minutes of ga induction. receiver operating characteristic (roc) curve analysis was used. the optimal cutoff was selected to maximize the youden index (sensitivity + specificity − ). the measurement of ivc-ci and/or Δvti were unsuccessful in seven patients ( . %). pih occurred in patients (incidence %). the areas under the roc curves ( figure ) preload responsiveness might be detected by the changes of cardiac index (Δcimini) induced by a "mini-fluid challenge" (mini-fc) of ml or even by the changes (Δcimicro) in response to a "micro-fluid challenge" (micro-fc) of ml. however, the smaller the fluid challenge, the larger the "grey zone" of diagnostic uncertainty. we tested whether ( ) micro-and mini-fc monitored by calibrated pulse contour analysis detect preload responsiveness and ( ) adding ml when the result of a micro-fc is within the grey zone improves diagnostic accuracy. in patients with circulatory failure, we infused ml saline over s followed by ml over s. we measured Δcimicro and Δcimini by the pulse contour analysis (picco ). preload responsiveness was defined by an increase in ci (Δciplr) during a passive leg raising test ≥ %. diagnostic uncertainty was described by calculating the grey zone after bootstrapping. Δcimicro were larger in responders than in non-responders ( . for the micro-fc, the area under the receiver operating characteristic curve was . ± . (threshold %), while it was . ± . for the mini-fc (threshold %). for the micro-fc, the grey zone ranged from . % to . % and included ( %) patients. for the mini-fc, it ranged from . % to . % and included ( )% patients, among which were already in the grey zone of the micro-fc. when evaluated by pulse contour analysis, micro-and mini-fc reliably detect preload responsiveness but with a large diagnostic uncertainty. it seems that adding ml more fluid to a micro-fc when its result is within the grey zone does not improve the diagnostic accuracy. the study is ongoing. the starling-sv bioreactance device (cheetah medical) reliably detects passive leg raising (plr)-induced changes in cardiac index (Δci). we tested whether it can also track the small and short-time Δci induced by the end-expiratory occlusion (eexpo) test, and whether shortening the time over which it averages cardiac output ( s in the commercial version) improves the detection. in mechanically ventilated patients, during a -sec eexpo, we measured Δci (in absolute value and in percentage) through calibrated pulse contour analysis (ci pulse , picco device) and starling-sv. for the latter, we considered both ci starling- provided by the commercial version and ci starling- obtained by averaging the raw data over s. we calculated the correlation between Δci pulse and both Δci starling- and Δci starling- , and the area under the receiver operating characteristic curve (auroc) to detect preload responsiveness, defined by a plr test. when considering absolute values, the correlation coefficient r between Δci pulse and Δci starling- was . (p= . ), which was lower than the one between Δci pulse and Δci starling- (rr comparison). when considering percentage changes, no correlation was observed between Δci pulse and Δci starling- . conversely, the correlation coefficient between Δci pulse and Δci starling- was . (p= . ), but it was lower than the one obtained for absolute values (p= . for r comparison). eexpo-induced Δci starling- , both in absolute values and in percentage, detected preload responsiveness with aurocs of . (sensitivity %, specificity %) and . (sensitivity %, specificity %), respectively. shortening the averaging time of the bioreactance signal increases the reliability of the starling-sv device to detect eexpo-induced Δci. moreover, the accuracy of the method is increased when absolute rather than percentage changes of ci are considered. fluids are among the most prescribed drug in intensive care, particularly among patient with circulatory failure. yet, very little is known about their pharmacodynamic properties and this topic has been left largely unexplored. there is a lack of strong scientific evidence in current guidelines for fluid administration in shock. several factors may impact the hemodynamic efficacy of fluids among which the infusion rate. the aim of this study was to study the influence of fluids administration rate on their pharmacodynamics in particular by studying mean systemic pressure (p ms ). we conducted a prospective observational study in patients with circulatory failure to compare two volume expansion strategies. when a patient required a fluid bolus, ml of normal saline were administered and several hemodynamic parameters were recorded continuously: cardiac output (co), arterial pressure (ap), mean systemic pressure (p ms ). infusion rate was let to the discretion of the attending physician and a "slow" and a "fast" group were determined based on the median of the infusion time. fluids effect was measured by the area under the curve (auc), maximal effect (e max ) and time to maximal effect (t max ) for each hemodynamic variable. results: p ms auc was higher in the "fast" group compared to the "slow" group (p= . ). we observed a shorter t max and a higher e max for p ms in the "fast" group compared to the "slow" group (p= . and . respectively). regarding co, t max was also shorter in the "fast" group (p= . ). auc and e max were similar between the two groups. fluid effect dissipated within minutes following the end of fluid infusion for every patient in both groups. the decreasing slope from maximal effect was comparable in the groups, for p ms and co alike. the effect of a ml fluid bolus in septic shock patients vanished within one hour. a faster infusion rate increased maximal effect and shortened the delay to reach it. study is ongoing. fluid management in the control arm of sepsis trials aa anparasan, ac gordon, mk komorowski imperial college london, department of surgery and cancer, london, united kingdom critical care , (suppl ):p in the past, high-volume intravenous fluid resuscitation in severe sepsis and septic shock was common. more recently, concerns over the harmful effects of this practice have led some clinicians to adopt less liberal fluid strategies. we sought to analyse temporal trends in fluid administration in the control arms of recent adult sepsis trials and assess any correlation with patient severity and mortality. a literature search was conducted to identify relevant randomized controlled trials that reported fluid administration published post . we recorded outcomes: total amount of iv fluid administered in the control arms of these trials between hospital admission and hour and hour following trial enrolment, mortality rates at the latest reported time point and apache-ii score at admission. we computed the pearson correlation coefficient and linear regression between study dates and the outcomes. we identified relevant trials [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , which recruited a total of , patients in their control arms, from to . the temporal analysis revealed no obvious trend in the in the total volume of iv fluid given by hour following trial enrolment (correlation p= . ) ( figure ). however, the total volume of fluid given by hour decreased significantly over the period of interest (r=- . , p= . ). in parallel, we observed a decrease in mortality (r=- . , p= . ) but there was no evidence of decrease in illness severity over time (p= . ). we found that in published rcts over the last two decades, the amount of intravenous fluid given to patients with sepsis in the initial hours did not appear to change, however less intravenous fluid was given over the first three days. upcoming large rcts will test the safety and efficacy of restrictive fluid administration approaches in sepsis. clinical practice guidelines recommend prompt intravenous (iv) fluid resuscitation for pediatric sepsis, including an initial fluid bolus of ml/kg [ ] . however, recent evidence is conflicting as to the effectiveness, volume, and consequences of aggressive fluid resuscitation in septic children. therefore, we sought to determine the epidemiology of early iv fluid resuscitation in an integrated health system, specifically at community hospital emergency departments (ed). we studied a retrospective cohort of pediatric patients (ages > month to < years) with sepsis identified in electronic health record data at community eds in southwestern pennsylvania from to . sepsis was defined as ) suspected infection (combination of fluid culture collection and administration of antibiotics and ) organ dysfunction (pediatric sofa score ≥ ) within hours of suspected infection. fluid bolus therapy was defined as electronic documentation of administration of . % normal saline iv bolus within hour of the time of sepsis onset. results: among , patients with pediatric sepsis, ( %) received iv fluid bolus therapy within hour of time of sepsis onset. the volume of fluid administered ranged from ml/kg to ml/kg (figure , panel a), corresponding to a median volume of ml/kg (iqr - ml/kg). patients who received ≥ ml/kg of fluids (n = , %) were younger (mean age years, sd vs. years, sd ; p< . ), more often had blood cultures collected during evaluation ( % vs. %, p= . ), and were more often transferred to another facility ( % vs. %, p< . ) when compared to patients who received < ml/kg of fluids (n = , %). mean fluid bolus volume within hour of time of sepsis onset by hospital ranged from ml/kg to ml/kg (figure , panel b) . in a cohort of community emergency departments, % of septic children received intravenous fluid boluses within one hour, and of those, only one half received volumes concordant with guidelines. (figure ). a wide range of fluid balance exists in septic shock patients cared for in icu. trends of serum albumin in septic and non-septic critically ill introduction: the link between hypoalbuminaemia and poor outcomes in critical care is well established [ ] . limited data are available on serum albumin trends during critical illness [ ] . in this study we assessed trends in serum albumin for up to days in both septic and non-septic critically ill patients. we retrospectively examined the records of adult patients admitted to critical care at the royal liverpool university hospital between and . we then excluded patients who did not have albumin data available for the first days, leaving us with patients. patients ( . %) had sepsis, and of these patients had died by day . of the non-septic patients ( . %), patients had died by day . albumin levels were collected for days from admission to critical care, in addition to other demographic and biochemical data. statistical analysis was performed using repeated measures analysis. septic patients had lower serum albumin than non-septic patients throughout the day period (p< . ). we observed a decrease in albumin by day in all groups, with levels increasing over the subsequent days. there was no difference in daily serum albumin between non-septic patients who survived or died. this is the first study, to our knowledge, to compare albumin trends in septic and non-septic critically ill patients over days. further research is needed to elucidate the optimal recipients and timing of albumin therapy. introduction: burn injury is characterized by marked inflammation, capillary leakage, and profound hemodynamic alterations. early albumin resuscitation is avoided fearing a paradoxical fluid escape into the interstitium. on the other hand, administration of crystalloids in massive amounts causes tissue edema and fluid extravasation, which deteriorates tissue perfusion by increasing oxygen diffusion distance. albumin administration could reduce the amount required to maintain hemodynamic stability in this population. we investigated whether albumin improves tissue perfusion and microcirculation by reducing tissue edema. this is an observational study conducted in the burn unit of maasstad hospital, rotterdam. patients with burns higher than % of total body surface area (tbsa) were included in the study. sublingual microcirculation was measured at admission (t ), (t ), and (t ) hours after burn injury. total vessel density (tvd) and functional capillary density (fcd) were analyzed. fluid management was calculated according to the modified parkland formula. albumin ( %) infusion was started hours after the burn insult. a total of nine patients were recruited between january and december . patients were included in the study after . ± . hours of the insult with a mean tbsa of ± %. the amount of crystalloid infusion was ± ml and ± ml at t and t ,respectively. within the first h (t ) ± ml albumin was given. tvd decreased from . ± . at t to ± . at t (p< . ) (figure ) introduction: spontaneous bacterial peritonitis (sbp) accounts for ≥ % of the bacterial infections that occur in patients with cirrhosis, and sbp has a high mortality rate ( % to %). albumin infusion has been shown to improve the outcome of sbp. the aim of this study is to examine the impact of albumin infusion on hospital length of stay (los) for cirrhotic patients with sbp. we utilized a nationwide electronic health record data set (cerner health facts®) to extract real-world data on adult patients (≥ years old) with cirrhosis and sbp who received antibiotics and admitted between january , , and april , . international classification of diseases (icd- / ) codes were used to identify cirrhosis and sbp. we used laboratory data for calculation of the model for endstage liver disease sodium (meld-na) score and vital signs data for calculation of the quick sepsis related organ failure assessment (qsofa) score at baseline for each encounter. a generalized linear model was used to assess the relationship between albumin infusion and hospital los. results: there were , encounters that identified patients with sbp and cirrhosis, of which , survived hospitalization. albumin was infused within hours of admission ('early albumin') in % (n= ), after hours in % ('late albumin', n= ), and not administered in % ('no albumin', n= ). meld-na was higher at presentation in early albumin cases versus late-or no-albumin cases (mean . and . ). unadjusted los was lower in patients receiving early albumin ( . days versus . days). risk-adjusted analysis demonstrated that early albumin led to a . % reduction in los ( % ci . %- . %, p = < . ). in these real-world data, albumin infusion within hours of admission in patients with cirrhosis and sbp was associated with a shorter hospital stay despite more severe illness. early albumin may not only improve clinical outcomes but may also reduce the costs of hospitalization in cirrhotic patients with sbp. early albumin use in patients with septic shock is associated with a shorter hospital stay: real-world evidence in the united states introduction: septic shock is among the most common critical care illnesses and incidence is rising, with mortality in excess of %. septic shock predisposes patients to multiple organ failure. while albumin is effective in management of circulatory dysfunction in septic shock, its utilization in this population is understudied in the us. we evaluated the impact of albumin utilization on hospital length of stay (los) among septic shock patients. we used a nationwide electronic health record data set (cerner health facts®) to extract real-world data on adult patients (≥ years old) with severe sepsis or septic shock, admitted between january , , and april , , identified by international classification of disease (icd- / ) codes, and receipt of antibiotics and vasopressors. we calculated the charlson comorbidity index (cci) and the acute physiology score (aps) at baseline. a generalized linear model was used to examine the association between albumin and hospital los, especially accounting for the timing of albumin infusion. we identified , unique visits for septic shock patients that survived to discharge. albumin was infused within hours of admission ('early albumin') in %, after hours ('late albumin') in %, and not administered in %. both cci and aps were higher, at presentation, in early albumin cases than late-or no-albumin cases (mean: . and . , and . and . , respectively). unadjusted los was slightly lower in patients receiving early albumin ( . days versus . days). a risk-adjusted analysis demonstrated that early albumin was associated with . % shorter los ( % ci . %- . %, p = . ). albumin infusion within hours of admission was associated with a shorter length of hospital stay. early albumin infusion may lead to better outcomes and reduced costs in patients with septic shock. further research is being conducted to assess other potential benefits of early albumin administration in this patient population. every new septic event follows by hemodynamic instability may lead sequentially to decreased organ perfusion, multiple organ failure. acute renal failure is recognized clinical feature during sepsis (up to - % in all cases). furthermore, urine output close monitoring is a cornerstone diagnostic clinical tool in each septic critically ill patient. in present study, we analyzed the dynamic minute-to-minute changes in the urine flow rate (ufr) and also the changes in its minute-to-minute variability (ufrv) during new septic event in critically ill patients. demographic and clinical data were extracted from the of critically ill patients who were admitted to the icu and developed new septic event (followed by fever and leukocytosis) and analyzed. a foley catheter was inserted into the urinary bladder of each study patient. the catheter was then connected to electronic urinometer, a collecting and measurement system which employs an optical drop detector to measure urine flow. the urine flow rate variability (ufrv) is defined and calculated as the change in ufr from minute to minute. results: ufr and ufrv both decreased significantly immediate after new septic episode until beginning fluid resuscitation (ppvalues < . ) (figure ) . statistical analysis by the pearson method demonstrated a strong direct correlation between the decrease in ufr, ufrv and the decrease in the map (r= . , p= . ; r= . , p= . ) ( figure ), and heart rate (r= . ,p=< . ) since systemic pressure starts to drop. ufrv and ufr demonstrated good clinical response to fluid administration despite the fact that systemic blood pressure did not improve (figure ) . we consider that dynamic changes in ufrv and ufr could potentially serve as a more sensitive signals ofclinicaldeterioration during the new septic event in critically ill patients.we also suggest that those parameters mightbeable to identify the optimal end-point of fluid resuscitative measures in septic critically ill patients. diminished urinary output (uo) is largely used as marker of acute kidney injury (aki) in critically ill patients. we aimed to explore the role of urinary output on incidence and mortality of aki developed during icu admission. the study population consists of all patients admitted between and to one of the dutch icus included in the nice database with an icu length of stay of at least hours, having daily measurement of creatinine and uo. only patients without renal replacement therapy that have a serum creatinine lower than . mg/dl ( . μmol/l) or a uo above . ml/kg/h on the day of the index icu admission were considered at risk for aki. patients were followed during their icu stay and classified according to the highest kdigo criteria reached based on creatinine alone (model ) and creatinine plus uo (model ) using icu admission serum creatinine as baseline. in both models, patients were classified as: no aki, renal impairment at the first day of icu admission, aki stage , aki stage , and aki stage . we identified , patients ( % male, mean age years, median icu-los days). of those, . % of patients had renal impairment at the first day of icu admission. among the remaining patients, . % in model and . % in model were classified as having no aki, . % and . % as aki stage , . % and . % as aki stage , and . % and . % as aki stage , respectively. survival at -day markedly differed according to the aki classification model used (figure) . similarly, adjusted hrs for -day mortality differed among patients with and without aki compared to patients with renal impairment at the first day of icu admission ( figure ) . among patients admitted to the icu % had renal impairment at the first day of icu admission. our findings suggested that uo plays an important role both on aki incidence and mortality and should be carefully interpret in the clinical setting especially in aki stage classification. introduction: acute kidney injury (aki) mostly attributed to renal tubular damage, has a high morbidity and mortality outcome [ ] , so a sensitive tool to assess the degree of tubular affection is needed for early detection and management of this condition. we investigated the ability of furosemide stress test (fst) (one-time bolus dose of mg/kg or . mg/kg if on prior furosemide-intake) to predict progression to akin stage-iii in critically ill subjects with early aki. we studied subjects; consecutive patients in group i receiving fst and consecutive patients in group ii receiving standard medical management for aki; patients ( . %) and patients ( %) met the primary endpoint of progression to akin-iii in groups i and ii respectively. patients with progressive aki had significantly lower urine output following fst in the first hours (p< . ). the area under the roc curves for the total urine output over the first hours following fst to predict progression to akin-iii was . (p = . ). the ideal-cutoff for predicting aki progression during the first fig. (abstract p ) . thirty-day survival according to aki classification model and model . hazard ratios (hrs) for -day mortality adjusted by sex, age, type of admission, apache iv score, sofa score at day of admission (excluded renal sofa score) for patients with aki classified with model and model fig. (abstract p ) . clinical correlation between urine flow rate variability (ufrv) and ufr and mean arterial blood pressure over new septic event (black arrows) and and after initial fluid resuscitation (red arrows). note: the ufrv and ufr decreased progressively in parallel with the falling mean arterial blood pressure and, than, rose again after the administration of fluids hours was a urine volume of less than milliliters with a sensitivity of . % and specificity . % group receiving fst. on the other hand, statistically significant hypotension, hypo-(kalemia, phosphatemia and magnesemia) occurred in group i. the fst in patients with early aki could predict liability for progression of aki, however it should be performed under adequate monitoring. introduction: ischemia-reperfusion (ir) causes renal dysfunction and damage. ir induces renal tubular injury triggered by hypoxia and hyperoxia, mediated by oxidative stress and inflammation. furosemide inhibits na + -k + - clcotransporter in the thick ascending limb of the renal medulla to decrease na + reabsorption, reducing oxygen consumption. we investigated if furosemide could improve renal oxygenation, function and damage by reducing o consumption and oxidative stress after ir. methods: wistar albino rats were divided into groups, with in each group; sham-operated control (c), control + furosemide (c+f), ir and ir+f. after anaesthesia (bl), min supra-aortic occlusion was applied to ir and ir+f groups followed by min (t ) and hours of reperfusion (t ). furosemide μg/kg/h infusion was simultaneously administered to c+f and ir+f after ischemia. systemic hemodynamic, renal blood flow (rbf), renal vascular resistance (rvr), renal oxygen delivery (do ren ), renal oxygen consumption (vo ren ), creatinine clearance (ccr), sodium handling, urine output (uo), cortical (cμo ) and medullar (mμo ) microvascular oxygenation were measured. results: rbf was reduced in ir ( . ± ) and ir+f ( . ± ) at t (p< . ) but it was further reduced in ir+f ( . ± ) (p< . ) at t compared to c and c+f. rvr was increased in ir ( ± ) and ir+f ( ± ) at t compared to c. rvr was normalized in ir ( ± ) but not in ir+f ( ± ) at t compared to c (p< . ). cμo and mμo did not differ between groups after ir insults (figure ). tissue o was reduced at the medulla, but not at the cortex in ir+f group compared to ir. do ren and vo ren were reduced in ir ( ± and ± ml/ min) and ir+f ( ± and ± ) at t (p< . ). pc was higher in ir+f ( . ± . ) compared to ir . ± . (p< . ). vo / tna + was increased in ir+f compared to ir. no change in ccr and uo was observed. furosemide after ir causes further impairment of renal perfusion, energy utilization and renal oxygenation resulting in renal damage. acute renal failure induced by hypoxemia: incidence and correlation study a trifi , h fazzeni , a mehdi , c abdennebi , f daly , y touil , s abdellatif , s ben lakhal la rabta hopital, medical intensive care unit., tunis, tunisia; la rabta hopital, tunis, tunisia critical care , (suppl ):p introduction: acute renal failure (arr) is a common complication in icus and usually caused by hypoperfusion. arf induced by hypoxemia is a concept rarely reported in icu. its incidence and pathogenesis are not well understood. we aimed to study the relationship between hypoxemia and the occurrence of arf. retrospective cohort study including patients with hypoxemia whatever its etiology between january and august . patients with chronic renal failure were excluded. arf was defined and ranked according to the kdigo criteria . arterial blood gas, urea, creatinine and clearance were reordered on the first, third and seventh days of evolution. results: patients were included and groups were obtained: group of hypoxemic patients with arf (arf+, n= ): versus group of hypoxemic patients without arf (arf-, n= ). the incidence of hypoxemie-induced arf was therefore %. clinical characteristics were comparable in both groups with a mean age of ± and a sex ratio of . . the comparative study showed in arf+ group: a lower ph ( . . ], p = . ). the most significant correlation was showed with mdrd clearance at day and p/f ratio at day (rho = . , p = . ). multivariate analysis found that septic shock and non invasive ventilation in hypoxemic patients were the factors related to arf with respectively or= . , % ci= . - . , p= . and or= . , % ci= . - . , p= . . overall mortality was % (n= ) and arf was an independent factor of mortality: or= , and % ci= . - . , p = . . hypoxemia-induced arf is a common complication associated with excess mortality. our study suggests that renal function is correlated with the degree of hypoxemia and that this correlation is rather distinct hours from hypoxemia. in preclinical models of sepsis, we have previously demonstrated that activation of amp activated protein kinase (ampk) using metformin, improves survival and organ function. thus, ampk activation is a potential therapeutic target in sepsis, and we hypothesize that exposure to metformin during sepsis is associated with decreased aki and mortality methods: retrospective analysis of a -hospital cohort of adult icu patients with type diabetes mellitus (t dm) who presented sepsis. we investigated if exposure to metformin during the hospitalization was associated with reduced -day mortality and aki. we used : propensity score matching (psm), propensity score stratification (pss) and propensity score weighting (psw) based on the probability to be exposed to metformin using covariates. for psm an exact match for insulin, amputation, cardiovascular diseases, retinopathy, charlson index, egfr, hba c, and apache iii, were used. sepsis was defined using sepsis criteria, and aki as kdigo stage or . from , patients, we found diabetic adults exposed to metformin during hospitalization and , who were not. metformin exposure during hospitalization is associated with decreased -day mortality and aki in septic adult patients with t dm. these findings suggest that metformin may constitute a potential therapeutic strategy in sepsis, and the potential role of ampk activation as a protective mechanism. however, studies are needed to confirm this association and the specific mechanisms of action. introduction: acute kidney injury (aki) may occur up to % in the intensive care unit (icu). predicting aki recovery may allow for risk stratification of patients, patient and family counseling, and early post-discharge renal care planning. however, predicting aki recovery at an early stage remains a challenge. methods: this is a retrospective study of the epanic multicenter randomized controlled trial database [ ] , which was split into development (n= ) and validation (n= ) cohorts, and patients experiencing aki stage and/or renal replacement therapy (rrt) in the icu were included [ ] . aki recovery was defined as being alive, without any stage of aki, and without need of rrt at hospital discharge. a logistic regression model with backward feature elimination was developed. the model performance was assessed by discrimination, calibration, and net benefit analysis, and internally validated with ten-fold cross validation. only the results in the development cohort are reported. of the patients who developed aki , patients ( . %) recovered from aki. the multivariable model selected age, bilirubin, heart rate, mean arterial blood pressure, surgical diagnostic group on icu admission, mechanical hemodynamic support on icu admission, suspected sepsis on icu admission as aki recovery predictors. the model had a mean area under the receiver operating characteristic curve (auroc) of . (standard deviation (sd) . ), mean calibration slope of . (sd . ), and mean calibration-inthe-large of < . (sd . ) (figure ). at the classification threshold that maximized sensitivity and specificity, mean net benefit with respect to treat-none was . (sd . ) and mean net benefit with respect to treat-all was . (sd . ). by using the routinely collected clinical data, the developed prediction model can fairly identify patients with a higher chance of aki recovery at hospital discharge. introduction: acute kidney injury (aki) is a frequent complication in critically ill patients and is associated with increased morbidity and mortality. sepsis is one of the most common cause of aki. a prospective study was conducted over months (january -june , ).we included patients with septic shock at admission or at any time during hospitalization.the aki staging was based on kdigo criteria.patients were divided into two groups, a group with aki (aki+) and a group without aki (aki-).then we compared the baseline characteristics, laboratory and physiologic data. patients with aki (aki+) were subdivided according to their prognosis. were enrolled patients. the mean (sd) age was . (± ) years.sex ratio was . . fifty-two ( %) patients developed aki.sapsii and sofa score in admission were higher in patients with kidney injury [ vs points (p= . ), . vs points ;(p= . )] respectively.the serum lactate level was significantly higher in (aki +) group patients during the first day of septic shock [ . ± . mmol/l (aki+)vs . ± . mmol/l(aki-);(p= . ) ] and its clearance was lower [( ± . % (aki +)vs ± %(aki-);(p= . )]. a significant difference was observed in c reactive protein level [ ± mg/l (aki +) vs ± mg/l (aki-) ; (p= . )].among (aki+) patients, kadigo iii was observed in . % of cases.nineteen ( . %) patients received hemodialysis.a normal kidney function was recovered in . % of cases.aki+ patients had a higher occurrence in disseminated intravascular coagulation ( vs patients, p= . ),acute respiratory distress syndrome ( vs patients; p= . ) and cardiac dysfunction ( vs patient, p= . ).mortality was higher in aki group ( % vs %; p= . ). the development of septic aki was associated with poor outcomes and prognosis.a better understanding of sepsis induced aki pathway will enable us to develop targeted therapeutic protocols.newer tools,permitting aki early detection, may make these therapies more fruitful. this study aims to show that contrast procedures do not significantly increase the risk of renal injury and should not be deferred. traditionally ciaki is the most important cause of in-hospital renal failure after nephrotoxic drugs and shock. problem is also the non-uniform definition of ciaki proposed by three different initiatives (akin, esur and kdigo). akin, being the most rigorous, defines ciaki as an increase in serum creatinine > . mg/dl or > % of baseline within hours. a retrospective observational single-centre cohort study analyzed patients who underwent a contrast procedure with iomeron . the first group underwent a ct pulmonary angiography (ctpa), and the fig. (abstract p ). internally validated model performance: (top row) roc curve; (middle row) calibration curve; (bottom row) decision curve second a coronary angiography with pci. no patient was previously prepared (raas blockade removal, crystalloid administration etc). we studied demographics, history of ckd and comorbidities and their impact on the ciaki by the akin criteria. a total of patients were divided into two groups (ctpa and pci). ctpa group ( m, f) all had acute pe and the pci group ( m, f) were treated for acs. the mean age was and years respectively. ckd was more prevalent in the pci group ( pt vs. pt) possibly explained by the more advanced atherosclerotic disease. advanced chd (nyha iii/iv) was found in pt (pci) vs. pt (ctpa) while diabetes and shock were equally distributed ( pt and pt) in both groups. the mean amount of contrast was significantly higher in the pci group ( . ml vs. ml). the mean creatinine/egfr measured before and after contrast in the ctpa group was . the goal of this study was to determine whether changing the body mass (bm) with fat-free mass (ffm) in cockcroft-gault (cg) formula could provide a more accurate prediction of aki in obese patients undergoing cardiac surgery. in this retrospective study, we reviewed institutional data of patients who underwent elective cardiac surgery in a tertiary referral university hospital. baseline patient creatinine value was collected and gfr was estimated using the mdrd, ckd-epi and cg formulas. cg formula was further modified by replacing the bm with ffm derived from the bioelectrical impedance analysis. postoperative aki was defined by kdigo creatinine change definitions. accuracy of the egfr values to predict the aki was calculated with roc-auc analysis. all the calculations were performed in different categories of bmi. figure ). the egfr is a poor predictor of aki in obese patients undergoing cardiac surgery. the ffm modified cauckraft-gault formula yield more accuracy in this specific group. retroaki: a ten-year retrospective study of acute kidney injury in intensive and progressive care units introduction: acute kidney injury (aki) is a frequent condition in intensive care units (icu) and progressive care units (pcu), affecting % to % of the patients, depending on the studied population and aki definition. aki has been identified as an independent risk factor of icu mortality and development of chronic kidney desease. the objective of this study was to describe the incidence of each aki stages as defined by kdigo definition (with evaluation of urine output, serum creatinine and initiation of renal replacement therapy (rrt)), in a mixed medical and surgical population of patients hospitalized in icu and pcu over a -year period ( - ). we included all patients who stayed more than hours in icu or pcu of edouard herriot hospital from may to january . data used to classify the patients were the urine output over a sixhour period, serum creatinine and the need for rrt, according to kdigo classification results: , hospital stays were analyzed. median icu/pcu length of stay was days [iqr: . - . ]. among icu patients, % had at least one aki episode graded , or and % had at least one severe episode (stage or ). among pcu patients, % had at least one episode of aki and % a severe episode of aki. patients had an average of . episodes of aki per stay. table represents the incidence of maximal aki stage during one stay. we found that urine output was the more frequent criteria to make diagnosis of aki stage or whereas rrt was more frequent for aki stage . this retrospective study reports a more important aki incidence in our icu/pcu than in previous studies. the difference could be fig. (abstract p ) . when comparing auc in different categories of bmi, the mcg appeared to be the only statistically accurate formula in patients with bmi - . explained by the difficulty to collect urine output from conventional database. serum creatinine and the use of rrt are often the only two criteria used to define and classify aki. these results confirm the high incidence of aki in icu and pcu and the importance to make an early aki screening of patients for whom preventive nephroprotective actions are needed. introduction: icu-patients with acute kidney injury (aki) requiring renal replacement therapy (rrt) are at risk for infections [ , ] . in this study we evaluated the incidence of infection in icu patients with and without less severe aki. finally, impact on outcomes was explored. this is a retrospective study on the pdms (protection data management system) of the adult icus of a university hospital. aki was assessed on kdigo criteria (creatinine (scr) and urine output), during the first -d of icu stay. infection was validated in the pdms by a team of icu specialists. results: during a -year period, a total of subjects were enrolled. aki was diagnosed in . % of patients during icu stay. aki patients were older ( vs. y, p= . ), had higher saps ( vs. , p< . ), and had more urgent icu admission ( % vs. %, p< . ). more aki patients had mechanical ventilation ( % vs. %, p< . ) and vasopressors on d- ( % vs. %, p< . ). aki stage , , and was present in . %, . % and . % of patients. more aki patients had infection ( % vs. %, p< . ) and increasing aki stages were associated with higher infection rates (aki- : %; aki- : %, aki- : %, aki- : %, p< . ) (figure ). we observed - times higher mortality in aki patients with infection, and a stepwise increase of mortality with increasing aki stages. after correction for infection and other confounders we found that all aki stages were associated with in-hospital mortality (ors aki- : . , aki- : . , aki- : . , all p< . ). over half of aki patients experienced an episode of infection and increasing aki severity was associated with higher infection rate. aki patients with infection had marked higher mortality, suggesting that infection was an important driver of outcome. however, after adjustment, aki stages had strong association with hospital mortality. several new biomarkers have been introduced to improve early diagnosis of acute kidney injury (aki). "nephrocheck" (nc; astute medical, usa) is a bedside test calculating "akirisk" (product of urinary concentration of the cell cycle arrest-markers timp- and igfbp ). several studies suggest the usefulness of nc in selected populations. however, the value of early routine measurement of nc is unclear. methods: therefore, we compared the prediction of a combined endpoint (cep: death < days and/or requirement of renal replacement therapy rrt) by nc within h of icu admission (nc ) and h later (nc ) with admission values of serum-creatinine, bun, cystatin c, urinary ngal, apache ii and sofa (roc-analysis). as a secondary endpoint we investigated the additional value of pathological measurements of nc ≥ . critically ill patients showed increased relative uce in the first days of icu admission, which may be attributed to higher protein catabolism. increased relative uce was associated with arc and both had no effect on -day mortality. introduction: this study compared epidemiology, short-and long-term outcomes for patients with community-acquired (ca) and hospital-acquired (ha) acute kidney injury (aki). we retrospectively analyzed all episodes of aki over a period of . years ( - ) on the basis of routinely obtained serum creatinine measurements in , patients whose creatinine had been measured at least twice and who had been in the hospital for at least two days. we used the "kidney disease: improving global outcomes" (kdigo) criteria for aki and analyzed the first hospital admission. a total of were admitted in hospital and fulfilled the inclusion criteria. average observation period per patient was days. the incidence of ca-aki among included hospital admissions was . % compared with an incidence of . % of ha-aki, giving an overall aki incidence of . %. patients with ca-aki were younger than patients with ha-aki ( vs . y) and had significantly less comorbidities, including preexisting cardiac failure, ischemic heart disease, hypertension, diabetes. patients with ca-aki were more likely to have stage aki ( , vs , %, p< . ) and had significantly shorter lengths of hospital stay than patients with ha-aki ( vs d, p< . ). those with ca-aki had better survival than patients with ha-aki (figure ; p< the evidence base for management of fluid removal during renal replacement therapy (rrt) is limited. a recent international survey revealed the extent of practice variation worldwide [ ] . our aim was to summarise the responses from europe-based healthcare professionals who participated in the survey. the international self-administered, cross-sectional, internet-assisted, open survey was disseminated between january and january via website links and emails to members of different critical care societies. results: participants from european countries completed the survey of whom ( %) were intensivists and ( %) worked in university-based hospitals. persistent oliguria / anuria was the most common indication for fluid removal ( % responders). the parameters which guided fluid removal included hemodynamic status ( % responders), cumulative fluid balance since admission ( % responders), and -hour fluid balance ( % responders). % of participants reported using crrt with a median net ultrafiltration rate ml/hr (iqr - ml/hr) for hemodynamically unstable and a rate of ml/hr (iqr, - ml/hr) for hemodynamically stable patients. only % of practitioners checked net fluid balance hourly ( % nurses, % physicians). new hemodynamic instability, defined as new onset or worsening tachycardia, hypotension, or need to start or increase the dose of vasopressors was reported to occur in % fig. (abstract p ). long-term survival patients (iqr . - . ). different strategies to re-gain hemodynamic stability were used. (figure ) main barriers to fluid removal were patient intolerance ( % physicians, % nurses) and interruptions in fluid removal ( % physicians, % nurses). the majority of participants agreed that guidelines and protocols would be beneficial. the practice of fluid removal during rrt is very variable across european countries. nurses and doctors identified a need for evidencebased protocols and clear guidelines. introduction: kidney disease improving global outcomes (kdigo) guidelines suggest the use of anticoagulation in continuous renal replacement therapy (crrt) [ ] . the effectiveness of the anticoagulation is important because replacing the hemofilter and tube interrupts crrt and increases total therapy time. regional citrate anticoagulation (rca) and unfractionated heparin (ufh) are most commonly using methods for crrt anticoagulation [ ] . the aim of this study was to investigate the efficacy, safety and metabolic differences of the patients in icu who underwent crrt and anticoagulation method changed from ufh to rca for different reasons. after ethics committee approval ( - / ) patients who underwent crrt between - at bursa uludag university hospital icu have been investigated and patients who underwent crrt by both rca and ufh included in the study. we divided patients in two groups (rca, ufh), demographic data (sex, age), sofa score, creatinine, urea, mean filter life time (flt) and ultrafiltration flow (uf), platelets, electrolytes (na, k, ca, mg), lactate, nahco and ph of groups at beginning and ending of first rca and ufh hemodialysis collected. we used t-test and bootstraps statistic tests. in agreement with other studies [ , ] , flt and uf was statistically significant lower in ufh group (table ) . there was no statistically significant difference in efficiency (urea and creatinine decrease), ph, lactate, nahco level, platelets count and electrolytes between two groups. to our knowledge, there are no studies comparing these two anticoagulation methods in the same patients. small number of patients and retrospective evaluation are limitations of the study. our results suggest that the implementation of rca method is safe and effective as ufh method with longer flt and uf. regional citrate anticoagulation during crrt in liver failure mj jain, pk kumar g, dg govil, jk kn, sp patel, ms shafi, rh harne, dp pal, sm monanga medanta the medicity, critical care, gurugram, india critical care , (suppl ):p continuous renal replacement therapy (crrt) with regional citrate anti-coagulation (rca) is increasingly being used as a treatment modality in critically ill patients. there is limited experience of use of citrate anticoagulation patients with acute liver failure and acute on chronic liver failure who pose a tough challenge of being at a higher risk for bleeding. an institutional protocol was formulated for use of commercially available citrate solutions and the same was studied to assess filter life and safety of citrate in liver disease. the primary objective was to assess safety of citrate anticoagulation in liver disease. this study was a single centre, prospective, non-randomized, single arm, observational study. all adult patients, with acute liver failure and acute on chronic liver failure requiring crrt were included. blood ionized calcium levels of . to . mmol/l was targeted throughout the therapy and total to ionized calcium ratio of less than . was maintained. rca was stopped if the ratio was more than . for consecutive assessments. incidence of citrate accumulation and toxicity were assessed. average filter life was also assessed. metabolic parameters, electrolytes and strong ion gap were followed till hours after completion on crrt. a total of patients were included in the study. nineteen patients of acute on chronic liver failure and patients of acute liver failure underwent crrt with rca. baseline average serum bilirubin, lactate and inr were . mg/dl, . mmol/l and . respectively. the average filter life was hours minutes. citrate accumulation took place in (n= ) patients and rca had to be stopped for ( n= ) patients due to the same. none of the patients had evidence of citrate toxicity. citrate anticoagulation was well tolerated in patients with acute liver failure in patients with or without pre-existing chronic liver disease on crrt. introduction: the intention of this study is to highlight the levels of citrate load for the general population that increases the risk of citrate complications (insufficient trisodium citrate delivery; net citrate overload and citrate accumulation) [ ] . this was a prospective data collection between february and march in a fourteen bedded critical care unit. eleven consecutive episodes of crrt were collected (a new episode characterized if crrt was discontinued for hours and above). one episode was excluded due to short duration (less than hours). patients undergoing rca-crrt received either a fixed or ml/kg/h effluent dose protocol. median patient age was , male %. average time on crrt was . days ( - ). % of the patients had complications, although % were minor ( figure ). all of the patients with net citrate overload had citrate loads of . mmol/h or above. the main risk factors were found to be shock and liver impairment which occurred in % of cases of which % developed complications. a fixed dose effluent protocol to standardise practice can potentially lead to a higher risk of minor complications. in our experience this is likely due to a lack of appropriate monitoring for rca-crrt complications. despite this, our complication rate of citrate accumulation is in line with that reported in literature. citrate loads in our ml/kg/ hr protocol were . % higher than our ml/kg/hr protocol and strongly related to higher complication rate that worsened in patients with risk factors for poor citrate metabolism. introduction: there is no optimal timing of continuous renal replacement therapy (crrt) in acute kidney injury (aki); however, it is based on volume overload, azotemia, hyperkalemia and severe metabolic acidosis [ ] . an important reason for metabolic acidosis in aki is increased unmeasured anions (ua) [ ] . delta-ph-ua (Δph ua ) detects the degree of metabolic acidosis caused by ua and is calculated by using 'the partitioned ph model' [ ] . in this study, we investigated whether Δph ua was a predictor to start crrt in patients with aki. the study was designed as a multicentric, prospective, observational study in . patients who were ≥ years old and diagnosed with aki [ ] were included. the moment aki was diagnosed, arterial blood gas, albumin, magnesium, inorganic phosphorus, urea, creatinine and Δph ua values were recorded. all patients were divided into two groups as crrt(-) and crrt(+) which consists of patients performed crrt due to traditional criteria. fig. (abstract p ) . incidence of complications introduction: continuous renal replacement therapy (crrt) is labor intensive and requires advanced nursing knowledge and skills. however, % of registered nurses (rn) are less than -year post-registration experiences in our unit. also there is an increasing demand of crrt from crrt days in to crrt days in . the obstacles for crrt in our department, includes variation of regimen, complicated workflow and insufficient training of nurses. a continuous quality improvement project is carried out to standardize the regimen, enhance workflow and provide structured training to nurses in the intensive care unit, to enhance nursing competence. methods: introduction: sepsis and septic shock is a leading cause of mortality in the intensive care unit. we tried to evaluate a novel hemoperfusion cartridge through a retrospective evaluation of patient's data in our centre. we used it as an adjuvant therapy in our patients with sepsis and septic shock due to varied causes. the aim of this study was to evaluate the efficacy of therapeutic hemoperfusion cartridge (hc-foshan biosun medical ® ) in the management of patients with sepsis. we retrospectively analysed data of group (n= sepsis) and group (n= sepsis+hemoperfusison; sepsis treated with hemoperfusion cartridge) admitted between to . group had received hemoperfusion cartridge as adjuvant therapy along with standard of care. demographic data, procalcitonin [ ] and leukocyte levels before and after therapeutic cytokine removal and duration of hc were recorded. while the mean duration of cvvhdf was . hours, the duration of hemoperfusion cartridge (application was . ± . hours). among patients who survived patients were administered hemoperfusion cartridge within hours of icu admission. there was a significant reduction in scores like apache and sofa score post hemoperfusion cartridge therapy procalcitonin and leucocyte levels after therapeutic hemoperfusion cartridge were found significantly lower than the pretreatment values (respectively p= . , p= . ). retrospective analysis showed significant reduction of vasopressors, and improvement in map in group . therapeutic hemoperfusion cartridge with cytokine removal applied with cvvhdf in septic patients have positive contributions to provide survival advantage. removal of activated leukocytes and endotoxin from the blood is a complex therapeutic effect of the device for removing endotoxin. in the main group ( patients with abdominal septic shock) after surgery, the traditional treatment was supplemented with two sessions of endotoxin removal ( hours each with an interval of hours) using "alteco lps adsorber" (sweden). the control group consisted of patients with a similar diagnosis and only traditional treatment. results: % of white blood cells were adsorbed in lps adsorber. among them, granulocytes ( %) were maximally extracted, then cd + monocytes (cd + mo) ( %), hla-dr + mononuclear cells ( %), monocytes ( %). il- , il- , procalcitonin (pct) were not adsorbed. the -day mortality rate in the main group was % and was lower compared to the control group - %. during monitoring, in the main group hours after the first removal of endotoxin, a decrease in the initially increased amount of activated cd + mo by . times, as well as functionally mature defensin + granulocytes (def + gran) by . times was observed. il- , il- , and pct decreased by . ; . ; and . times, respectively. during this period, the control group showed an increase in cd + mo and def + gran, while il- , il- did not change, and pct increased . times. a day after the second removal of endotoxin and then days later, the main group of il- , il- , and pct continued to decline. in the control group, only il- decreased after days, the rest continued to grow. the cellular adsorption of endotoxin-bound cd + mo and mature def + gran is an important part of the mechanism of action of the endotoxin removal device. does the endotoxin adsorption of pmx column saturate in hours? preliminary study c yamashita in the euphrates trial, the polymyxin b-immobilized fiber column (pmx) hemoperfusion (hp) had no significant effect on -day mortality. endotoxin (lps) burden by endotoxin activity assay > . may exceed μg [ ] , so the dose and duration of pmx-hp could be insufficient to lower the lps burden. to confirm this issue, we experimented in a closed-circuit with h continuous lps addition, and pmx can adsorb > μg [ ] . further, lps concentration became constant within h in the single lps spike test for determining pmx-hp duration [ ] . to prove our hypothesis that the single lps spike test reflects the adsorption equilibrium, and not saturation, we added lps intermittently to reaction. methods: lps ( ng/ml) was mixed with ml deactivated fetal calf serum as a reflux solution, as previously described [ ] ; this concentration is much higher than that observed in septic patients. we created a closed circuit that incorporates pmx- r at / th the amount of an adult pmx and performed pmx-hp at ml/min for h. lps was added in two shots (post h: ng, ng/ml; post h: ng, ng/ml). lps was measured using the limulus amebocyte lysate test at , . , , , , and hr. after an initial decrease between and h, lps concentration did not decrease between and h after pmx-hp initiation. post lps pulse addition at h, it increased and then decreased till h. futher, it did not decrease between and h, but it increased and then decreased again after lps pulse addition post h (figure ). lps adsorption rates were . , . , and . % at , , and h, respectively. conclusions: lps adsorption capacity of pmx- r was maintained even after two additional shots of lps, suggesting that the constant lps concentration in the previously reported lps spike test might be indicative of adsorption equilibrium rather than saturation. a coohort study included patients admitted to three intensive care with sepsis / septic shock ( sepsis criteria ) and aki ( akin score). all patients were submitted to cvvhdf with the oxiris filter (baxter, usa) . the main clinical data, il , procalcitonin, endotoxin ( eaa ) and sofa score were evaluated at basal time ( t ) and at the end of the treatment ( t ). all data are expressed as mean ± sd or median and iqr . anova test was used to compare the changes in the time. results: patients were submitted to rrt with the oxiris filter for ± hours . patients had aki stage , patients aki stage and patients had aki stage. at t all groups had an high vasopressor fig. (abstract ) . lps concentration in lps pulse addition test support to maintain map ≥ mmhg. il , procalcitonin eaa and sofa total were also elevated with no difference between the groups. at t creatinine improved better in aki ( p< . vs. t ) and in aki ( p< . vs t ) then in aki group. map increased in aki ( p< . vs t ) and aki ( p < . vs t ) , but not in aki group. il , procalcitonin decreased more in aki ( p < . vs t ) then aki . at t sofa total was higher in aki then aki ( p< . ) and aki ( p< . ). conclusions: aki and aki stage patients submitted to bp with the filter oxiris respond better then aki stage patients . -this transalte in a better clinical course. -crrt with oxiris filter is useful in septic patients with aki, but aki stage septic patients represent an high risk group. a non-interventional, multicenter, non-randomized patient registry for multiple organ dialysis with the advos system multiple organ failure is a challenging problem in the icu. as an advanced dialysis system, the advos procedure can eliminate watersoluble and protein-bound substances, regulate the acid-base balance as well as fluid and temperature. in , a national registry was established to collect data under "real-life" conditions of patients treated with advos without any trial-specific interventions (drks id: drks ). methods: data from / to / from german hospitals (university hospitals in hamburg-eppendorf, mainz, essen, and klinikum weiden) were analyzed. clinical parameters, treatment settings and adverse events were documented. the -and -day mortality rates were compared with extrapolated rates based on the sofa score. results: patients with a median age of years (iqr - ), of whom ( %) were male, were evaluated. patients had a median sofa score of (iqr: - ) before the st advos treatment, which is associated with an expected mortality of %. the number of failing organs was (iqr - ): cardiovascular ( %), lungs ( %), liver ( %), kidneys ( %), coagulation ( %) and cns ( %). treatments with a median duration of (iqr: - ) hours were evaluated. were discontinued, of which ( %) were due to a device error. adverse events were documented, were related to the device (all due to clotting and recovered without sequelae). significant removal of protein-bound (bilirubin: . vs . mg/dl) and water-soluble toxins (bun vs and creatinine . vs . mg/dl). in addition, improvement in acid-base balance was observed: ph ( . vs. . ), bicarbonate ( . vs. . mmol/l) and base excess (- . vs. . mmol/l) ( table ) . -and -day mortality rates were % and %, respectively. in a cohort of patients with multiple organ failure, we observed an improvement in the expected mortality rate, especially if the advos procedure was applied early. adverse events are comparable to other dialysis therapies in intensive care patients. introduction: acute kidney injury (aki) due to ischemia-reperfusion affects onethird of the patients in cardiac surgery. we investigated the potential role of cyclosporine (csa) to prevent postoperative aki and mitigate inflammatory response to extracorporeal circulation (ecc). methods: double-blind, randomized, placebo-controlled single-center study. patients (n= ) scheduled for elective cardiac surgery were randomized to , mg/kg csa or placebo before the surgery. the primary objective was to assess the role of csa to reduce the incidence of postoperative aki. the secondary objective was to study csa induced changes in the inflammatory response to ecc. results: all enrolled patients were analyzed. postoperative aki was more pronounced in the cyclosporine group compared to placebo. or= . ( . - . ), % ci. the cytokine production in response to ecc was not affected by cyclosporine (figure ) . in patients undergoing cardiac surgery, a single preoperative dose of csa does not prevent the postoperative decrease in renal function. csa does not alter cytokine release in response to extracorporeal circulation. elevated post-ecc levels of pro-inflammatory cytokine il- are associated with kidney dysfunction and may be predictive. new generation adsorbent such as oxiris r was introduced as novel technique in renal support for critically ill patients [ ] . septic shock patients require decatecholaminization strategies emphasizing blood purification to remove catecholamine-producing mediators and evacuate overload fluid in interstitials. our -year-old female patient, admitted to icu after surgery with history of ovarium cancer. her septic shock was worsened with ards, hypercoagulable state and aki. vasopressors were set. patient was controlled with mode simv ,ps ,tv ml,peep ,fio %. renal support was implemented by diuretic and cvvh started on the second day. at first,regular adsorbent was used, post-filter mode was set, and periodic fluid removal target was ml/h. but after hours, no significant changes observed. oxiris r added and after hours passed, requirements of vasopressors reduced, tidal volume increased, hemodynamic parameters stabilized, urine production increased. it was continued for days and patient was recovered. our patient had fallen into inadequate cars stage in which not able to counter septic effects on vital organs (figure ). renal would be primary target for filtration and monitoring tool. adsorbent consisted of an and polyethyleneimine was useful to purify blood from endotoxins conjoined with slower filtration. continuous yet cautious process in cvvh evacuate fluid and mediators while maintain steady hemodynamics. biomarkers could not be evaluated due to limited resources, but improving parameters could be signs that showed recovery process had already took place. advanced hemofiltration is a privilege. implementing and enhancing it with new generation adsorbent would increase survivors by extracting unnecessary fluids and eliminating catastrophic endotoxins and mediators. consent to publish: written informed consent for publication was obtained from the patient. analysis of retrospective cohort study data of patients (pt) treated for dka at icu of kaunas clinics during - has been carried out. serum kalemia, glycemia; hypokalemia, hypoglycemia episodes; rate of insulin interruption for hypo-and normoglycemia during ketoacidosis; use of nah co for ketoacidosis, and los in icu were analysed. spss . was used for statistic calculations. traits evaluated as significant at p < . . at the beginning of dka treatment in totally hypokalemia ( . ± . mmol/l) was recorded in / pt ( . %). due to ignoring of blood ph ( . - . ( . ± . ) kalemia was falsely misinterpreted as "normo-" or "hyper-" . - . ( . ± . mmol/l) in / pt ( . %), thus disregarded so complicated by obvious hypokalemia additionally in / pt ( . %). in hypokalemia los in icu was . ± . vs . ± . h, p < . . insulin use has caused hypoglycemia ( . - . ( . ± . mmol/l)) in / pt ( . %), los in icu . ± . vs . ± . h, p < . .insulin use was interrupted in case of normoand hypoglycemia with still persisting ketoacidosis in / pt ( . %), los in icu was found to be . ± . vs . ± . hr, p < . . nah co was given for symptomatic treatment of ketoacidosis during first h of dka in / pt ( . %) with stable hemodynamic: hco - buffer has increased ( . ± . - . ± . mmol/l), p < . , but it didn't control ketoacidosis, and los in icu was . ± . . vs . ± . h, p < . . hypokalemia, hypoglycemia, precocious interruption of insulin use were recorded as complications of dka treatment. all of them have prolonged los in icu. symptomatic treatment of ketoacidosis with nah co had no effect on it, and prolonged los in icu as well. a growing interest exists about co derived parameters in shock management. central venous-arterial pco difference (p cv-a co ) is strictly related to cardiac output; central venous-arterial pco difference to arterial-central venous o content difference ratio, p cv-a co / c a-cv o , has been proposed as anaerobic metabolism when it's > . mmhg/ml [ ] . to evaluate p cv-a co /c a-cv o reliability in detecting anaerobic metabolism, we analyzed it in consecutive patients affected by mala admitted to our icu, considering these patients as a prevalent anaerobic metabolism model. we calculated, by douglas formula, central venous-arterial co content difference to arterial-central venous o content difference ratio, c cv-ca co /c a-ccv o , as a respiratory quotient surrogate. we performed arterial and central venous blood gas analysis simultaneously at admission, we calculated p cv-a co , p cv-a co /c a-cv o and c cv-a co /c a-cv o and we recorded scvo . we verified relationship between p cv-a co /c a-cv o and scvo and arterial ph, arterial lactates, sofa score at admission and c cv-a co /c a-cv o by linear regression analysis. pcv-aco /ca-cvo greatly increases in mala ( . ± . ). pcv-aco / ca-cvo (fig. ) shows significant co-variation with ph (r = . ; p= . ) and sofa score at admission (r = . ; p= . ). pcv-aco / ca-cvo has poor agreement with ccv-aco /ca-cvo (r = . ) and disagrees with it in identifying anaerobic metabolism, in our series, in fact, ccv-aco /ca-cvo is, in patients, < like an aerobic rq value. pcv-aco /ca-cvo shows better agreement with ph, sofa score and lactate level than scvo . in our series, p cv-a co /c a-cv o is good illness and acidosis severity marker, but it seems to be affected by ph value in accord with haldane effect [ ] . p cv-a co /c a-cv o , in our study, doesn't seem to be a reliable anaerobic metabolism marker nor a rq surrogate. it is thought that early administration of basal insulin to patients with diabetic ketoacidosis (dka) may improve outcomes. small studies have shown trends towards decreases in time to closure of anion gap (tcag), rates of rebound hyperglycemia following discontinuation of intravenous (iv) insulin, rates of hypoglycemia, intensive care unit (icu) length of stay (los), and hospital los [ ] [ ] [ ] [ ] . this was a single-center, retrospective chart review of our institution's dka protocol between january and august . patients that received early basal insulin within hours of initiation of iv insulin and before closure of the anion gap (ag) were compared to those that did not receive early basal insulin. the primary outcome was median tcag. secondary efficacy outcomes include: time on iv insulin infusion, time to de-escalation of level of care, hospital los, and re-elevation of ag. secondary safety outcomes included incidences of hyperglycemia, hypoglycemia, and hypokalemia. a total of patients were identified meeting inclusion and exclusion criteria. median tcag was longer in the experimental group ( vs. hours, p < . ). incidence of re-elevation of ag and incidence of hyperglycemia were lower in the experimental group. other outcomes were similar (figure ). early administration of basal insulin to patients with dka resulted in a longer tcag with a lower incidence of re-elevation of ag and hyperglycemia. early administration of basal insulin appears to be safe with respect to hypoglycemia and hypokalemia. glycaemic control continues to be a challenge in critically ill patients. stress induced hyperglycaemia has been associated with increased morbidity and mortality [ ] . conversely, patients receiving intensive glucose control have a higher risk of death [ ] . a quality improvement project was designed to develop a comprehensive insulin protocol that recognized pre-existing diabetes and reduced hypoglycaemia. data was collected prospectively in all adult patients admitted to the rah intensive care unit (icu) between october and august from the national icu audit database and electronic patient records. daily figures were collected for numbers of hypoglycaemic episodes (< mmol/l), "in range" ( - mmol/l) blood sugar measurements and patients with a pre-existing diagnosis of diabetes. data was collected and analysed using microsoft excel. results: patients were identified; patients ( . %) had pre-existing diabetes. a total of blood sugar measurements were reviewed; ( . %) were "in range" and hypoglycaemic episodes ( . %) occurred. there was no significant correlation between number of diabetic patients and measurements within range. of note, there was an increase in number of measurements per patient in the second half of the time period ( vs ). the development of this protocol has improved glycaemic control in our icu. there are considerably fewer episodes of hypoglycaemia and a large proportion of blood sugar measurements are in range. we hope to continue data collection and interrogate the prevalence of pre-existing diabetes further to reduce glycaemic variability. the optimal management of blood glucose levels for critically ill patients remains unclear. hypoglycemia, hyperglycemia and glycemic variability are associated with mortality. the time in targeted blood glucose range (tir) has been suggested to correlate with mortality depending on the status of antecedent glycemic control, but it has not been verified optimal tir and whether there is an optimal disease-specific tir. a retrospective observational study was performed at a single center. in the present study, we enrolled all critically ill patients admitted in intensive care unit from january to october. patients with diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome and patients who had < blood glucose readings were excluded. gathered information included, in part, demographics, comorbidities, severity of illness scores, diagnosis at admission, length of icu stay and hospital discharge status. the primary outcome was -day mortality. we analyzed to find the optimal tir for critically ill patients. several tirs were each tested for correlation with mortality. a total of , patients, . % of whom had diabetes, were studied. tir to mg/dl (or, . ; %ci, . - . ), tir to mg/ dl (or, . ; %ci, . - . ) and tir to mg/dl (or, . ; %ci, . - . ) > % was independently associated with mortality in critically ill patients respectively. the optimal tir did not differ depending on diagnosis at admission. in this retrospective evaluation, tir to mg/dl > % was independently associated with mortality in critically ill patients, especially those with good antecedent glucose control. these findings have implications for the design of future trials of intensive insulin therapy. the prevalence of chronic dysglycemia (diabetes and prediabetes) in patients admitted to swedish intensive care units (icus) is unknown. we aimed to determine the prevalence of such chronic dysglycemia and asses its impact on blood glucose control and patient-centred outcomes in critically ill patients. in this retrospective, observational study, we obtained routine glycated hemoglobin a c (hba c) measured in patients admitted to four tertiary icus in sweden between march and august . based on previous diabetes history and hba c we determined the prevalence of chronic dysglycemia (prediabetes, undiagnosed diabetes and known diabetes). we compared indices of acute glycemic control in the icu and explored the association between chronic dysglycemia and icu-associated infections, mechanical ventilation, renal replacement therapy, vasopressor therapy, and mortality within days. of patients, ( %) had chronic dysglycemia. of these patients, ( %) had prediabetes or undiagnosed diabetes and fig. (abstract p ) . results ( %) had a known diabetes diagnosis. during icu stay, patients with chronic dysglycemia had higher average blood glucose, spent less time in target glucose range, had greater glucose variability, and were more likely to develop hypoglycemia than patients without chronic dysglycemia. chronic dysglycemia was associated with greater need for renal replacement therapy (odds ratio . , % ci . - . ) and increased -day mortality (hazard ratio . , % ci . - . ) after adjustment for simplified acute physiology score . in contrast, chronic dysglycemia was not associated with mechanical ventilation, vasopressor therapy, or icu-associated infections. in four tertiary swedish icus, measurement of hba c showed that / of patients had chronic dysglycemia (prediabetes or diabetes). chronic dysglycemia was associated with marked derangements in glycemic control during icu stay, greater need for renal replacement therapy and with increased mortality at days. case report: modern antidiabetic therapie causes ketoacidosis am heiden, m emmerich krankenhaus bad oeynhausen, institut für anästhesie, bad oeynhausen, germany critical care , (suppl ):p the modern antidiabetic class of sglt -inhibitors, that are known to reduce the risk for cardiac events [ ] , are increasingly used in the last few years. a -year old male patient with diabetes mellitus suffered days after colectomy surgery from abdominal pain and nausea. the patient had an antidiabetic therapy with empaglifozin that was paused until day after surgery (nutrition start on day , weaning on day ). methods: this is a case report of one male patient seen in the icu setting. daily blood values including arterial blood gases, vital parameters and clinical status of the patient were observed and evaluated. the blood gases showed this metabolic acidosis: ph . ; pco . mmhg, bicarbonate mmol/l, be - . mmol/l, lactate . mmol/l, glucose mmol/l. a ketonuria despite normal blood glucose values was noticed, so that the diagnosis of ketoacidosis was clear. after analyzing the possible causes we found out, that empaglifozin in times of catabolism and fasting can cause this severe symptomatic. we terminated the therapie with empaglifozin and under the treatment with insulin the symptoms disappeared within days and the patient could be discharged from the icu on day after surgery. after one episode of ketoacidosis the therapy with sglt -inhibitors should lifelong never be started again. we recommend that intensivists should be aware of the modern sglt -inhibitors because of the shown severe complications and the increased use of this medication. consent to publish: written informed consent for publication was obtained from the patient. while obesity confers an increased risk of death in the general population, numerous studies have reported an association between obesity and improved survival among critically ill patients. this contrary finding has been referred to as the obesity paradox. this retrospective study uses two causal inference approaches to address whether the survival of non-obese critically ill patients would have been improved if they had been obese. the study cohort comprises , adult critically ill patients hospitalized at the intensive care unit of the ghent university hospital between and . obesity is defined as a body mass index of ≥ kg/m . two causal inference approaches are used to estimate the average treatment effect in the untreated (atu): a naive approach that uses traditional regression adjustment for confounding and that assumes missingness completely at random, and a robust approach that uses super learning within the targeted maximum likelihood estimation framework and that uses multivariate imputation of missing values under the assumption of missingness at random. obesity is present in . % of patients. the in-hospital mortality is . % in non-obese patients and . % in obese patients. the marginal associational risk difference for in-hospital mortality between obese and non-obese patients is - . % ( % confidence interval (ci) - . % to . %, p= . ). the naive approach results in an atu of - . % ( % ci - . % to - . %, p= . ), whereas the robust approach yields an atu of - . % ( % ci - . % to . %, p= . ). a robust causal inference approach that may handle confounding bias due to model misspecification and selection bias due to missing data mitigates the obesity paradox, whereas a naive approach results in even more paradoxical findings. the robust approach does not provide evidence that the survival of non-obese critically ill patients would have been improved if they had been obese. bowel management within an icu environment is often difficult. recent data collection from an intensive care unit at the rvi identified either loose stool or constipation on > % of patient days. it was postulated this could be improved with a more tightly controlled bowel management regimen. to test this hypothesis a step-wise bowel protocol was created and introduced. data was collected in the month period following its implementation with the following aims: ) assess effectiveness of the protocol ) further observe the reasons for loose or constipated stool on an diarrhea is an important problem in each critically ill pateints [ ] . we aimed to investigate the frequency and management of diarrhea in our icu. in this study patient retrospectively reviewed, in our icu between . . - . . . patients were divided into two group as diarrhea "positive" and "negative". patients with diarrhea had fluid or loose stools or more times a day. each diarrhea period of the patients with diarrhea was examined separately and compared with the group without diarrhea. nutritional status, enteral product formulation, leukocyte, neutrophil, albumin values, gastric sparing, antibacterial and antimycotic use, los in hospital and in icu were compared. in diarrhea positive group, on the day of hospitalization, laxative and/or enema administration, toxin a in stool, nitrogen balance before and after diarrhea, enteral product change in diarrhea, probiotic, metronidazole or oral vancomycin use were examined. the incidence of diarrhea was . %. the most common diagnosis of icu admision was respiratory failure ( - %) in both groups. diarrhea occurred in two days after laxative and/or enema treatment. enteral nutrition was higher in both groups (≥ %). nasogastric tube feeding was significantly higher in the diarrhea group (p= . ). there was no difference between nutritional product formulation and diarrhea development (p> , ). antibacterial use was high in both groups ( %); however, teicoplanin use was significantly higher in the group diarrhea negative group (p= . ). the los in icu, and hospital was higher in diarrhea group (p< . ). no difference in mortality rates (p> . ). many factors may cause diarrhea in icu, and diarrhea may adversely affect patient treatment and increase morbidity. we think that preventive methods are as important as the treatment of diarrhea. the use of parenteral glutamine is studied in number of rcts and systemic reviews (heyland d , wischmeyer p ), while there is a lack of data about the use of enteral glutamine. the aim of our study was to determine the effect of enteral glutamine supplementation on the incidence of hospital infections and death. design: retrospective cohort study. inclusion criteria: males and females > years of age, tbsa burned %- %, nasogastric intubation.patients were divided in two groups: glutamine group (n= ) and control group (n= ). in the study group enteral glutamine was administered to the patients for days after admission to the icu. baseline characteristics were well balanced between groups. no significant difference was found between groups on patients' age, sex, tbsa, need for mechanical ventilation and rate of inhalation injury. primary outcome was all-cause mortality. secondary outcome was rate of nosocomial infections (skin and skin structure infections (sssi), lower respiratory tract infections, urinary tract infections, bacteremia, sepsis). mortality rate was ( %) and ( %) in the glutamine group and the control group, respectively, p= . . rate of nosocomial infections was ( %) in the glutamine group and ( %) in the control group, respectively, р= . . rates of sssi, lower respiratory tract infections, urinary tract infections and sepsis did not differ significantly between the groups: ( %) and ( %), p= . ; ( %) and ( %), р= . ; ( %) and ( %), р= . ; ( %) and ( %), р= . , respectively. rate of bacteremia was significantly different between the groups: ( %) in the glutamine group and ( %) in the control group, p= . . retrospective design is a significant limitation of our study. enteral glutamine supplementation may reduce the incidence of bacteremia in burn patients, but has no influence on the incidence of other nosocomial infections and mortality. further large clinical trials are needed. with outcomes were assessed with multivariable logistic regression and cox proportional hazard analyses, adjusted for baseline risk factors and randomization. in sensitivity analyses, models were further adjusted for key regulators of ketogenesis to assess whether any effect was direct or indirect. late pn increased plasma hb as compared with early pn, with maximal effect on day (p< . for day to and for the "maximal effect" day in the patients). adjusted for baseline risk and randomization, plasma hb associated with a higher likelihood of earlier live weaning from mechanical ventilation (p= . ) and of earlier live picu discharge (p= . ). as plasma hb replaced the effect of the randomization, the hb effect statistically explained these benefits of the randomization. further adjustment for key regulators of ketogenesis did not alter these findings. plasma hb did not independently associate with the risk of infections and mortality. withholding early pn increased ketogenesis in critically ill children, an effect that statistically mediated part of its clinical benefits. critical care patients are prone to frequent feeding interruptions for various reasons including feeding intolerance. these interruptions can lead to adverse outcomes. the aim of the study was to determine the reasons for and the duration of interruptions of enteral nutrition (en). single-center observational, cross-sectional study in a -bed mixed icu of a tertiary hospital. duration: months. patients, aged . years old (± . ), that stayed in the icu > hrs and were fed with en were included. anthropometric data, bmi, time of initiation of prescribed en, type of en formula, daily calories delivered were recorded. energy intake was calculated according to espen guidelines ( kcal/ kg bw/day). the causes for and duration of interruption were reviewed from the patient's chart. apache ii and mnutric score was calculated for all patients. mnutric score ≤ was used to diagnose malnutrition. all patients included in the study were endotracheally intubated. apache ii was . ± . . % of patients had increased risk of malnutrition. icu stay was . ( . ± . ) days, and the in-hospital mortality was %. there were episodes of en interruptions over a median icu stay of . days. median . interruptions/patient. the most common reason for en interruption was gastric residual volume monitoring followed by diagnostic and therapeutic procedures (figure ). other reasons include surgery, intolerance and/or delayed feeding and extubation. the median lost feeding time was . hours/ day ( . - . ) for all causes, while the mean loss of total energy intake was kcal/day (± )/day. average body weight of the patients was kg (± ). caloric deficit was calculated at kcal/day or % of the prescribed caloric goal. the results of this study showed that interruptions can lead to substantial caloric deficit, malnutrition and adverse events. an interruptionminimizing protocol could be useful in order to reduce the missing hours and to improve the clinical outcomes. relationship of goal-directed nutritional adequacy with clinical outcomes in critically ill patients pc tah there are controversies surrounding the effects of optimal nutritional intake on clinical outcomes in critically ill patients. this study aimed at investigating the relationship of goal-directed energy and protein adequacy on clinical outcomes which includes mortality, intensive care unit(icu) and hospital length of stay (los), and length of mechanical ventilation (lomv). this was a single centre prospective observational study. nutritional requirements were guided by indirect calorimetry and -h urinary urea.nutritional intake was recorded daily until death, discharge, or until day of icu stay. clinical outcomes were collected from patient's hospital record. the relationship between the two groups (< % and ≥ % of overall nutritional requirement) with mortality outcomes was examined by using logistic regression with adjustment for potential confounders. terlipressin, despite being one of the main treatments for acute variceal bleeding, may lead to severe hyponatremia due to its antidiuretic activity.we aimed to identify risk factors for development of hyponatremia during terlipressin treatment. retrospective study of patients admitted to acute intermediate care unit for hypertensive upper gastrointestinal bleeding due to chronic liver disease who received terlipressin(december -decem-ber ).hyponatremia was defined as a decrease in na serum levels ≥ meq and severe hyponatremia as > meq within days of treatment. we studied patients, . % male, mean age of . years (sd . ). alcohol-related liver disease was the most frequent etiology. hyponatremia occurred in patients ( . %). serum na Δbetween - and - meq and serum na Δ>- meq occurred in . and . %, respectively (table ) . severe hyponatremia occurred in patients ( . %) and symptoms were reported in two cases (status epilepticus and altered mental status). patients with higher baseline levels of na were more susceptible to terlipressin-induced hyponatremia and a longer length of stay was observed in patients with serum naΔ>- meq ( . vs . days, p< . ). the prevalence of hyponatremia in our study was lower than previously reported.higher serum na at admission and aih as etiology of cirrhosis were predictors of terlipressin-induced hyponatremia. neither the cumulative dose of terlipressin nor the duration of treatment appear to be related to the development of hyponatremia a Δ h-[na] > mmol/l was associated with larger hazards of mortality ( figure ). an increase in serum sodium in the first hours of icu admission is independently associated with a higher mortality in patients admitted with mild hyponatremia, normonatremia, and hypernatremia. based on our findings, it is possible that mild hyponatremia may be a protective mechanism in critical illness, which questions common practice of routinely correcting serum sodium when it is too low. introduction: acute liver failure (alf) represents a life-threatening organ dysfunction associated with increased mortality and liver transplantation represents the only definitive treatment. the aim of this study was to assess the effects of renal replacement therapy in combination with hemoadsorption in alf patients. twenty-nine patients with alf admitted to the intensive care unit (icu) of fundeni clinical institute were included in the study. after icu admission, consecutive session of hemoadsorption in combination with continuous veno-venous hemodiafiltration were applied. number of organ dysfunctions and sirs criteria were recorded at icu admission. the following data were recorded before and after the hemoadsorption therapies: glasgow coma scale, pao /fio , creatinine, -hours urine output, bilirubin, leucocyte and platelet count, heart rate, mean arterial pressure and vasopressor support, c-reactive protein and procalcitonine. clif-sofa score was calculated before and after the therapy. icu length of stay and -days outcome were noted. the mean age in the study group was ± years. the median number of sirs criteria was [ , ] and the median number of organ dysfunctions was [ , ] . the use of hemoadsorption was associated with a decrease in creatinine (from . ± . to . ± . mg/dl, p= . ), bilirubin (from . ± . to . ± . mg/dl, p= . ) and platelet count ( ± / ul to ± /ul, p= . ). we also observed a decrease in clif-sofa score from . ± . to . ± . (p= . ). overall mortality was . % (n= ). six patients ( . %) underwent liver transplantation with % -days survival. the use of hemoadsorption in patients with alf is associated with improvement in liver and kidney functional tests and may represent a new therapy in bridging these patients to liver transplantation. introduction: impairment of intestinal mucosal barrier function is the initiating factor of sepsis. in order to explore the effect of lactic acid bacteria on intestinal barrier function impaired by sepsis, it is necessary to establish sepsis and lactic acid bacteria ecological models. however, how to construct these models is still unclear. co-cultures with a gradient of lactic acid bacteria and caco- cells were constructed. the symbiotic state was observed under an inverted microscope and lactate dehydrogenase (ldh) toxicity tests, transepithelial electrical resistance(teer) tests and western blots were used to determine effective concentrations of lactic acid bacteria in monolayer cell models. lipopolysaccharide (lps) was used to treat cells, and cell counting kit- , quantitative reverse transcription pcr(rt-qpcr) and enzyme linked immunosorbent assays (elisa) were used to determine the appropriate concentration for sepsis models. the number of living cells decreased significantly when the moi(number of lactic acid bacteria/cell number) reached ( figure , panels a, b). the release of ldh indicated that damage to cells began to increase when the moi exceeded (panels a, b). at an moi of . , resistance values began to increase over time, whereas resistance values began to decrease when the moi reached (panel ). as the number of lactobacilli increased, the expression of tight junction protein increased and then decreased (panel a, b, c). in sepsis model experiments, the cell survival rate began to decrease once the concentration of lps exceeded ^ ng/ml (panel ). rt-qpcr results showed that ng/ml lps significantly increased inflammatory cytokines (panel ), and elisa results consistently showed that tnf-α and il- increased significantly when lps concentrations reached ng/ml (panel a, b). it is feasible to construct a cell monolayer model of lactic acid bacteria and lps. the appropriate moi of lactic acid bacteria is . and the optimal concentration of lps is ng/ml. introduction: sepsis is associated with high mortality and morbidity. as the severity increases, physiological parameters such as ph changes are one of the most notable features in metabolic acidosis secondary to high lactate. currently there is no point of care test other than blood gas measurement that could detect these ph changes. this is challenging especially in prehospital environment. the aim of this study is to develop a novel rapid point of care testing using a sensor to detect ph change in blood. sensors were produced by screen printing graphene and silver electrodes and functionalizing the graphene working electrode with an active layer of melanin. a preclinical sensor model was produced by adding lactic acid to a citrated plasma sample thus altering its ph over a clinically relevant range. the ph sensors were exposed to modified plasma, recording any changes in the voltage. the relationship between the voltage potential and plasma ph was established using weighted least squares regression. a ph dependent change in the measured voltage, with respect to the ph of the solution, was observed with a sensitivity of - . mv/ph +/- . over a physiologically relevant ph range between ph . and ph . . in this first phase proof of concept study a low cost, ph sensor was fabricated and demonstrated to be effective in measuring the ph of the plasma. this is the first time that such a sensor has been demonstrated and validated to work in this preclinical model of acidosis. the technology demonstrated here is a promising candidate for a point of care test whereby abnormal blood ph levels can be detected and monitored outside of a laboratory environment in a rapid manner. further studies are now underway to detect this change in whole blood. (figure ) . over one year only a small proportion of patients (n= , %) were classified as 'intermediate high' risk and potential candidates for reperfusion therapies. the revised national early warning score (news) with modified glasgow prognostic score (mgps) is superior to the news for predicting in-hospital mortality in elderly emergency patients t mitsunaga jikei university school of medicine, emergency medicine, tokyo, japan critical care , (suppl ):p the national early warning score (news) was developed in the ukto identify the risk of death. the previous study showed that the modified glasgow prognostic score (mgps) correlate with frailty in elderly patients [ ] . the aim of this study is to evaluate the predict value of the revised news with mgps for in-hospital mortality (in days) in elderly emergency patients. this study is secondary analysis and was carried out in jikei university kashiwa hospital, in japan, from april to march . the acute medical patients aged and older were included. the news was derived from seven physiological vital signs. the mgps was derived from c-reactive protein (crp) and albumin. discrimination was assessed by plotting the receiver operating characteristics (roc) curve and calculating the area under the roc curve (auc). the aucs for predicting in days in-hospital mortality were . for revised news with mgps and . for the original news. the auc of the revised news with mgps was significantly higher than that of the original news for predicting in-hospital mortality (p < . ) (figure ) . our single-centred study has demonstrated the utility of the revised news with mgps as a high predictor of acute phase in-hospital mortality in elderly emergency patients. the diagnostic performance of the five main emergency department (ed) triage systems has been shown to be poor in distinguishing acute coronary syndromes (acs) from mild severity diseases in chest pain patients. these ed triage systems are either clinically-based, being more sensitive or ecg-based, more specific [ ] . the goal of the study was to evaluate if incorporation of cardiovascular risk factors (cvrf) into ecgbased triage could increase his diagnostic performance. cecidoc is a prospective, observational, single-center study in an academic hospital. all consecutive adult patients admitted for acute chest pain were included. we compared the ecg-based french triage system [ ] to a modified system upgrading patients with a normal ecg but significant cardiovascular risk from a low acuity triage score (waiting period before medical assessment of max. min.) to a high acuity triage score (waiting period before medical assessment of max. min.). the final diagnosis was determined after a -day follow-up. we predefined as being adequate a high-acuity triage score (level or ) for acs and a low-acuity score (level , or ) for mild severity diseases. a total of patients was enrolled over a -month period (age . ± . ; m/f ratio . ). triage scores of patients ( . %) with acs were compared to patients ( . %) with mild severity diseases. taking into account cvrf, the sensitivity of the triage system increased from to % whereas the specificity decreased from to %. area under the roc curve (auc) went from . to . (fig. ) . for chest pain triage at ed, addition of cardiovascular risk factors into ecg-based triage increases his diagnostic performance. approximately % of patients presenting to hospital with an intentional overdose require admission to an intensive care unit (icu) [ ] . there are currently no uk guidelines regarding the optimal use of ct head scans (cth) in this patient cohort [ , ] . this study aims to determine whether we should be performing ct head scans in obtunded patients with suspected overdose requiring admission to intensive care. we performed a retrospective search of the icnarc database for plymouth university hospital trust, looking for patients admitted to the icu with overdose or self-poisoning as a primary diagnosis. patients were identified and of these patients required intubation due to obtundation(gcs< ). there were males and females with an average age of years old. the median length of stay on the unit was day. of the patients has a past medical history of mental illness, and overdosed on prescribed medications. the average gcs recorded on admission was . of the ( %) patients had a cth on admission, of which were part of a trauma scan. were known overdoses and were suspected overdose as per the cth request form. the main rationale behind those requests were to exclude additional intracranial injury. none of those cth showed any signs of acute pathology (figure ) . in this retrospective study, obtunded patients with suspected or known overdose with no history of apparent trauma or injury do not benefit from cth. in the absence of a history of trauma or focal neurological signs our conclusions are that cth provides limited value in the management of these patients. the audit was carried out to objectively investigate the problems associated with technique of folley catheterization in emergency department and indoor units of internal medicine wards [ ] . introduction: cellular and molecular mechanisms, epigenetic aspects of acute clozapine poisoning are studied insufficiently. the aim of this study was to identify morphological and epigenetic alteratons in brain neurons during acute exposure to clozapine combined wit ethanol. the experiments were carried out on male wistar rats weighting - g (n= ). group i (control) received . % nacl solution enterally; group iiclozapine mg/kg in . % nacl solution; group iiiclozapine mg/kg in % ethyl alcohol. after hours euthanasia was performed. autopsy included withdrawal of brain samples for histological examination (n = ) and for determination of global dna methylation level (n = ). the global dna methylation level ( -mc%) was determinated by fluorimetric method. inter-group comparisons were made by kruskal-wallis test. histological examination of paraffin sections of brains stained with hematoxylin and eosin was performed by light microscopy. in acute сlozapine poisoning and its combination with ethanol morphological changes in neurons of the cerebral cortex were detected. in acute сlozapine with alcohol poisoning an increase of global dna methylation level was observed. probably the identified changes have a common pathogenesis which will be clarified in our further studies. there is limited information available regarding the prevalence of adder bites and the complications of envenomation. nhs data suggests there are adder bites annually in the uk with the last fatality in [ ] . we performed an audit into adder bites in south west wales to identify the number attending our emergency departments, their management and clinical course as well as any environmental factors that predict increased likelihood of being bitten or the severity of the bite. a retrospective study of adder bites attending emergency departments in south west wales was undertaken (jan to aug ). measurements included were patient demographics, clinical presentation, type of treatment (conservative vs anti-venom) and outcome. results: patients were included, age range - years ( figure ). the majority of bites occurred in sand dunes ( . %) and all bites were on extremities. anti-venom was administered to . % ( / ) of patients. there was a significant positive association between the use of anti-venom and the length of hospital stay (r = . ; p= . ) and a significant negative correlation between the anti-venom use and both diastolic and systolic blood pressure (p= . and . respectively p= . ). all patients fully recovered. in this study, we demonstrated that with a full clinical assessment on presentation it is safe to decide whether anti-venom is required. the current guidelines are safe and effective in the treatment of adder bites. μmol/l, for pao < . kpa and > . kpa, platelets < * ^ /l and > * ^ /l, and bilirubin > μmol/l. in our population of adult ed patients, the thresholds of vital values associated with increased -day mortality were very close to routinely used values, and most of the thresholds were included in the lowest urgency level in triage and risk-stratification scoring systems. the workload in the emergency room: direct assessment by the therapeutic intervention scoring system- and indirect assessment by the nasa task introduction: the number of emergency room admissions continues to increase each year, which increases the care workload of the emergency department staff, who should to use its theoretical and practical knowledge in order to provide quality care in difficult working conditions. the aim of our study was to assess the emergency room staff workload its impact on health workers and patients and to suggest an improvement strategy to decrease this workload. a prospective, monocentric cohort study with descriptive and analytic approach over one month (december ) conducted at the emergency department of an academic hospital. the workload endured by the emergency room staff was evaluated by the nasa task load index and on patients by the therapeutic intervention scoring system- . there were cumulative days of hospitalization in consecutive patients admitted to the emergency room. the average age was ± years. the average length of stay at the emergency room was about ± h. the average tiss- score was . ± . . factors associated with important care workload were: age ≥ years, diabetes, more than comorbidities, the use of intravenous antibiotics; the use of vasoactive drugs and the use of mechanical ventilation; a high tiss score was predictive of emergency room mortality. in the indirect assessment of the care workload, medical and paramedical staff were interviewed, % of them were under years old with a sex ratio of . . a high level of mental and physical workload was expressed by ed staff with considerable level of frustration; the ed staff suggested mainly to improve the working conditions, communication and to redefine tasks "who does what". our study had shown a significant workload in the emergency room, a process to reduce this workload is being implemented medical simulation is a modern teaching tool increasingly used in specialties such as anesthesia, emergency medicine and obstetrics. however, it's not widely used in specialties like cardiology, althought cardiovascular emergencies are very frequent. the purpose of our study was to assess the effectiveness of simulation-based medical education in the management of cardiovascular emergencies among moroccan graduate students. we conducted a prospective, observational, multi-centrer study including the students of three moroccan universities from the th to the th year of medicine who underwent phases: first a pre-test, then a theoretical and practical training on cardiovascular emergencies after which the students were separated in two groups, one undergoing the medical simulation training (group ) and one who didn't (group ), followed by a theoretical then a practical post-test on resusci anne and simman®. at last, the students were asked to answer a satisfaction survey. the reform procedure in the tunisian army consists in repairing the physical damage and deciding on the applicant's ability to continue working. terrorism increases the impact of the co-morbidity generated and the socio-economic consequences that result from it. the purpose of this work was to study the epidemiological, clinical and evolutionary profile of terrorist injuries, to specify the rates of consequent partial permanent disability (ppi) and the possibilities of returning to work. descriptive retrospective cross-sectional study of reform files on military personnel injured during anti-terrorist operations from fig. (abstract ) . changes in total bcpr rate in family-and friends-witnessed ohca cases with dispatcher-assisted instruction during -week period after the day of disaster during three years january to september . the data collection was carried out on the basis of a collection form. our wounded were male, % of whom belonged to the army. the average age was years and months ± . . half of our wounded were troopers. infantry and special forces were the most exposed military units. half of the accidents were recorded in the kasserine region ( cases). chronic post-traumatic stress disorder (cptss) was found in injured, followed by amputations in injured. the after-effects were psychological in %, physical in % and mixed in % of our injured. the ppi rate ranged from % to % in . % of injuries.. more than half of the injured had returned to their professional activity, % were put on reform for health reasons. our results showed that the esptc was the most recorded sequel, and that the ppi rate was significant in a quarter of our injuries. in our series, a third of our wounded were put on reform for health reasons. to state the importance of initial care and adequate and rigorous follow-up to recover a greater number of war wounded. introduction: the rapid response system (rrs) has been shown to decrease hospital mortality [ ] . the japanese coalition for patient safety has set a major goal for hospitals to more widely implement the rrs. however, prevalence and actual circumstances of use in acute care hospitals (including small scale hospitals) in japan are as yet not well-known. web-based questionnaires were sent to acute care hospitals (of scale beds-or-larger) of prefectures in western japan. each participant hospital selected a certain department which answered the questionnaire. the rrs included the medical emergency team (met), the rapid response team (rrt), and the critical care outreach team (ccot). we investigated the presence and circumstances of in-hospital emergency calls, rrs and other systems, and then illuminated issues to be solved. our study suggests that delays in patient transfer to the icu after rrt activation in the wards were associated with slower physiological improvement.these findings support further and larger studies. blood and blood products use in intensive care unit m akcivan, s bozbay, o demirkiran istanbul university cerrahpasa, anesthesiology and intensive care, istanbul, turkey critical care , (suppl ):p blood and blood product (bp) transfusions are frequently used in intensive care units (icu) [ ] . it is important to know transfusion epidemiology and the effect of adverse transfusion reactions and their effect on mortality and morbidity.we aimed to investigate the blood and bp transfusions in the icu. blood and bp transfusions in icu, between - were reviewed retrospectively. we evaluated each transfusion as a data and examined the pre-and post-transfusion laboratory values, demographic data, cause of icu admission and comorbidities. results: patients who underwent transfusion in the icu, and transfusion data from these patients were included. the most frequent cause of hospitalizations were respiratory failure and sepsis. the rate of patients transfused in the five-year period decreased from . % to . %. the hemoglobin threshold before transfusion decreased from . g / dl to . g / dl. a total of transfusion reactions were observed and the most common transfusion reaction was febrile non-hemolytic reaction. the most commonly transfused product was red blood cell suspension. transfusion reactions were found to be slightly higher in men than women in young age group(< y) (p = . and p= . , respectively). transfusion reactions were found to be more frequent in emergency transfusions (p < . ). the number of transfusions was significantly lower in patients with apache ii score < (p < . ). the need for transfusion was found to be higher in patients with hematological malignancy (p < . ). it was observed that as the mean number of transfusions increased the mortality is also increased (p < . ). transfusion therapies are the treatments that are vital but have a serious mortality and morbidity risk. in particular, intensive care patients should be considered in detail because of their specific features. restrictive transfusion practices have positive results. association between anemia or red blood cell transfusion and outcome in oncologic surgical patients. figure a) . the association between rbc transfusion and adverse events also remained after adjustment (or . [ . - . ] ; p < . ) ( figure b) . in oncologic surgical critically ill patients, there was an independent association between anemia (even moderate anemia) or rbc transfusion and patient outcomes. our findings highlight the need for further research to determine the optimal transfusion strategy in surgical oncologic patients. transfusion impaired skin blood flow when initially high e cavalcante dos santos, w mongkolpun, p bakos, al alves da cunha, c woitexen campos, jl vincent, j creteur, fs taccone erasme hospital, intensive care department, brussels, belgium critical care , (suppl ):p red blood cell transfusion (rbct) increases global oxygen delivery (do ) and may improve microcirculation. however, the effects on blood flow have been found to be conflicting. we studied icu patients with stable hemodynamic status (mean arterial pressure (map) ≥ mmhg for at least hours) and without active bleeding, who received a rbct. skin blood flow (sbf) was determined (periflux system , perimed, index finger; perfusion unit, pu) together with map, heart rate (hr), hemoglobin (hb), lactate levels and scvo before and after rbct. sbf was measured before rbct (t ) and after (t ) for each min. according to previous data indicating the lowest sbf value found in noninfected icu patients was pu, all patients were analyzed according to the baseline sbf (i.e. < pu -low sbf vs. ≥ puhigh sbf). the relative change of sbf (Δsbf) was calculated after rbct and the responders were defined by the function of > %. results: icu patients were studied. rbct was associated with increases in map and scvo but no change in sbf. at baseline, scvo was lower in the responders than in the non-responders (p= . ) and lower in patients with low sbf than in the high sbf (p= . ). there was no difference in hb, map, and lactate, between the patients with low and high sbf. after rbct, map rose in the responders (p< . ) and in the non-responders (p= . ), sbf (p< . ) rose in patients with low sbf, and sbf (p= . ) decreased in patients with high sbf. there was a negative correlation between baseline scvo (r= - . , p< . ) or baseline sbf (r= - . , p< . ) and the relative increase in sbf after rbct. rbct increases skin blood flow only when it is impaired at baseline. severe immune dysregulation is associated with adverse outcomes and is common in intensive care unit (icu) patients [ ] . erythropoietin-stimulating agents (esas) have both anti-apoptotic and immune-modulating properties [ ] . despite potential benefit, both the safety and efficacy of these agents remains unclear [ ] . here we evaluate the impact of esas on morality at hospital discharge in critically unwell adult patients admitted to the icu. we conducted our search strategy in accordance with a predetermined protocol. the use of ffp is associated with an increased incidence of complications such as acute respiratory distress and infections, and the rate of complications increased with the quantities of ffp transfused [ ] . pcc contain several important coagulation factors and it has been suggested that they could replace ffp. this has been shown mainly in case reports or series in which coagulation factor deficit was detected by using poc viscoelastic tests in trauma [ ] or traditional hemostatic tests in obstetric patients [ ] . multicenter observational study of the safety and efficacy of the prothrombin complex concentrate. a survey of anesthetists was conducted in maternity hospitals at various levels of care in the russian federation. data has been collected and processed. as a result, patients were analyzed. pph was determined as a volume of blood loss more than ml during vaginal delivery or cs. the most significant risk factors for pph were: preeclampsia or arterial hypertension and a history of postpartum hemorrhage. . % had no risk factors for pph. it was determined that the use of prothromplex iu decreased the number of patients with transfusion ffp - ml/kg by . % and increased the number of patients without transfusion by . %, compared with patients without use of prothromplex iu (figure ). no complications were detected. the use of pcc safety and efficacy reduce use of ffp during pph. the full analysis included patients on either hfc (n= ) or cryoprecipitate (n= ). the intraoperative and postoperative changes in etp and fibrinogen concentration are shown in table . for fibtem a (intraoperatively) and fibrinogen concentration (intraoperatively and postoperatively), the mean numerical values appeared higher with hfc than cryoprecipitate. fxiii (hfc: . %, . %; cryoprecipitate: . %, . %, at baseline and hr after surgery start), fviii and vwf were maintained throughout surgery in both treatment groups. this was also the case for laboratory tests activated partial thromboplastin time, prothrombin time and platelet count. the forma- coagulation parameters analyses showed broad overlaps between hfc and cryoprecipitate, with satisfactory maintenance of the clot quality parameters, fxiii concentrations and thrombin generation parameters. the study group includes men and women with a mean age of , vs. . years (p= . ) admitted with the diagnosis of multiple trauma. we found a directly proportional and highly significant statistical correlation between base excess and fibrinogen level diagnosed using the mcf/fibtem parameter(r= . , p< . )and an inverse proportional correlation between lactate level and fibrinogen level (r= - . , p= . ). in the roc analysis that uses as a variable the level of base excess and as a criterion of classification the fibrinogen deficit (mcf/fibtem< mm) it can be observed that at a value of be<- mmol/l, we can diagnose a fibrinogen deficit with a sensitivity of . % and a specificity of . % (auc= . ,p< . ). lactate appears to be inferior to the excess base (figure ) , but still has a good diagnostic power, a value of . mmol/l has a sensitivity of . % and a specificity of % (auc= . ,p< . ). the difference between the two roc curves ( . ) is statistically significant (p = . ). both base excess and serum lactate can be used to diagnose fibrinogen deficiency with the mention that base excess appears to have a higher sensibility and specificity ability. based goal-directed algorithm. this approach requires further clinical validation. we conducted a retrospective study comparing transfusion strategies in patients with major trauma between and . we retrieved demographic data and blood products administered from patients with at least one red-blood cell (rbc) transfusion. primary outcome was a reduction of rbc administration. secondary outcomes were mortality, icu length of stay and acute kidney injury. we included patients admitted in the icu due to severe trauma (sapsii: . ± . ), and mainly after emergent surgery ( . %). they featured a mean age of . ± . y, were predominantly male ( . %) and % were in shock. in the first hours of hospital admission a mean of . ± . rbc units were administered. most patients received a fibrinogen-based protocol (fbp) ( %), with an average of ± g of fibrinogen and ± fresh-frozen plasma (ffp) units, versus ± g of fibrinogen and ± ffp units in the ffp group. the fbp was associated with a decrease administration of rbcs in the first hours (r = - . ; p < . ), even after adjustment for severity (p= . ) and for tranexamic acid use (p = . ). it was associated also with a decrease of platelet transfusion (p= . ). fibrinogen-based protocol was not associated with a decrease in mortality, acute kidney injury or noradrenaline dose. treatment of tic in past years has progressively changed to a goaldirected fibrinogen-based approach. in our population, the use of fbp lead to a reduction of rbc administration in severe trauma patients. prospective, multicenter, randomized study comparing administration of clotting factor concentrates with a standard massive hemorrhage protocol in severely bleeding trauma patients the objective of this study was to assess the ability of the quantra® qstat® system (hemosonics) to detect coagulopathies in trauma patients. many level trauma centers have adopted whole blood viscoelastic testing, such as rotational thromboelastometry (rotem®, fig. (abstract ) . study treatment plan instrumentation lab) for directing transfusion therapy in bleeding patients. the quantra qstat system is a cartridge-based point-of-care (poc) device that uses ultrasound to measure viscoelastic properties of whole blood. and provides measures of clot time, clot stiffness and a test of fibrinolytic function. methods: adult subjects were enrolled at two level trauma centers which use a rotem based protocol to guide transfusion decisions. study protocols were approved by the site's ethics committee. for each subject, whole blood samples were drawn upon arrival to the emergency department and again, in some cases, after administration of blood products or antifibrinolytics. samples were analyzed on the quantra (at poc) in parallel to rotem delta (in lab). a total of patients were analyzed. approximately % of samples had a low clot stiffness (cs) values suggestive of an hypocoagulable state. the low stiffness values could be attributed to either low platelet contribution (pcs), low fibrinogen contribution (fcs), or a combination ( figure ) . additionally, % of samples showed evidence of hyperfibrinolysis based on the quantra clot stability to lysis parameter. samples analyzed on standard rotem assays showed a lower prevalence of low clot stiffness and fibrinolysis based on extem, fib-tem results. the correlation of cs and fcs vs equivalent rotem parameters was strong with r-values of . and . , respectively. this first clinical experience with the quantra in trauma patients showed that the qstat cartridge detected coagulopathies associated with critical bleeding and may be useful for directing blood product transfusions in these patients. ability to perform testing at poc may provide additional clinical advantage. the objective of the study was to describe the conditions of use of fibryga® g, a new, highly purified, human fibrinogen (hf) recently granted a temporary import authorization for use in congenital and acquired fibrinogen deficiencies in france. observational, non-interventional, non-comparative, retrospective study conducted in french hospital centres using fibryga®. data from patients with fibrinogen deficiency having received fibryga® from december to july were retrieved from their medical files. indications, modalities, efficacy and safety outcomes were recorded. indications encompassed non-surgical bleeding (nsb) either spontaneous or traumatic, including post-partum hemorrhage (pph), bleeding during surgery (sb) or administration to prevent bleeding during planned surgery. treatment success was defined as control of the bleeding or hemoglobin loss < % for bleeding treatment and as absence of major perioperative hemorrhage for pre-surgical prevention. this analysis included patients aged , ± . years and % were male. all presented an acquired fibrinogen deficiency requiring administration of hf. indications were nsb (n= , . %) including ( . %) pph, sb (n= , . %), and prevention of sb (n= ; , %). cardiac surgeries were the main procedures associated with treatment and prevention of sb. mean total doses of fc were . ± . g, . ± . g and . ± . g for nsb, sb and prevention of sb. success rates were . % ( %ci . - . %), . % ( %ci . - %) and . % ( %ci . - %) respectively. for pph, mean dose of hf was . ± . g with a success rate of . % ( %ci . - %). overall, tolerance was good. fibrinogen concentrate fibryga® is mostly used for bleeding control. in one third of patients, hf was administered preventively to avoid bleeding during surgery. use of fibryga® was associated with favourable efficacy outcomes. functional testing for tranexamic acid effect duration using modified viscoelastometry t kammerer , p groene , s sappel , p scheiermann , st schaefer ruhr-university bochum, institute of anaesthesiology, heart and diabetes center nrw, bad oeynhausen, germany; ludwig-maximilans university, department of anaesthesiology, munich, germany critical care , (suppl ):p tranexamic acid (txa) is the gold standard to prevent or treat hyperfibrinolysis [ ] . effective plasma concentrations are still under discussion [ ] . in this prospective, observational trial using modified viscoelastometry we evaluated the time-course of the antifibrinolytic activity of txa in patients undergoing cardiac surgery. methods: patients were included. modified viscoelastometry (tpa-test) was performed and txa-plasma-concentration, plasminogen-activatorinhibitor- (pai- ) and pai-antigen-plasma-concentrations were measured over h. additionally, in vitro dose-effect-curves from blood of healthy volunteers were performed. data presented as median with interquartile range (q /q ). results: txa plasma-concentration was increased compared to baseline (t : μg ml - ) at every time-point with a peak concentration min (t ) after application (p< . ; see fig. a ). lysis was inhibited from min (lysistime tpa-test : p< . ; lysisonsettime tpa-test :p< . ). maximumlysis tpa-test was decreased at t (t : % ( / ) vs. t : % ( / ); p< . ). of note, after h some patients (n= ) had normalized lysis whereas others (n= ) had strong lysis inhibition (ml< %;p< . ) up to h. high and low lysis groups differed regarding kidney function (cystatin c: . mg l - ( . / . ) vs. . mg l - ( . / . );p= . ) and active pai- ( . ng ml - ( . / . ) vs. . ng ml - ( . / . );p= . ). in-vitro, txa concentrations > μg ml - were effective to inhibit fibrinolysis. in our trial, after h there was still completely blocked lysis in patients with moderate renal impairment. this could be critical with respect to postoperative thromboembolic events [ ] . here modified viscoelastometry could be helpful to detect the individual fibrinolytic capacity. introduction: peri-operative coagulopathy correction based on viscoelastic hemostatic assays (vhas) and single-factor coagulation products has changed the paradigm of bleeding management in cardiac surgery [ ] . in a retrospective study, we analysed patients with emergency surgery for thoracic acute aortic dissection (taad), before and after the introduction of fibrinogen concentrate in clinical practice. data were collected from paper and electronic records. the study was approved by the institutional ethical committee. patients were included in the analysis, operated in , before fibrinogen concentrate was approved for human use, and in - . therapy was guided by a rotational thrombo-elastometry (rotem) algorithm. exclusion criteria were non-compliance with the institutional protocol and intra-operative death. we investigated allogeneic blood transfusion (abt), fibrinogen use, peri-operative bleeding (pob), surgical reexploration and post-operative complications (poc). the groups were similar in gender, age, body weight, additive euro-score and aortic cross-clamp time. fresh frozen plasma, cryoprecipitate and red blood cell transfusion were lower in the fibrinogen group, but not platelet transfusion (table). , % of patients in the study group received fibrinogen concentrate and median dose was g (iqr - ). day postoperative chest tube drainage and surgical reexploration were significantly lower. there were no differences in stroke, renal replacement therapy, mechanical ventilation time and icu stay. in patients with taad surgery, rotem-guided algorithms which include fibrinogen concentrate are associated with less (pob), surgical re-exploration and abt. further research is needed to document the role of vhas and concentrated factors in reducing (poc). andexanet alfa (aa, portola pharmaceuticals, san francisco, ca) represents a modified factor xa agent which is approved antidote for apixaban and rivaroxaban. andexanet alfa may also neutralize the anti-xa effects of betrixaban and edoxaban. this study aims to compare the relative neutralization of these four anti-xa agents by andexanet alfa in different matrices. andexanet alfa was diluted at mg/ml. apixaban (a), betrixaban (b), edoxaban (e) and rivaroxaban (r) were diluted in ph . , . m tris buffer (tb), blood bank plasma (bbp) and in % albuminated buffer (ab) at . - . ug/ml. anti-xa activities of all four agents were measured in three systems and the reversibility indices of aa were profiled. the reversibility index (ri ) of anti-xa effects by aa was determined at - ug/ml. each of the four agents produced varying degrees of inhibition of anti-xa at . - . ug/ml, the ic ranged . - . ug/ml in bbp, . - . ug/ml in ab and . - . ug/ml in tb. andexanet alfa produced a concentration dependent reversal of all four anti-xa agents. in the bbp, the ri values for a ( ug/ml), b ( ug/ml), e ( ug/ml) and r ( ug/ml). in the ab, the ri values for a ( ug/ml), b ( ug/ml), e ( ug/ml) and r ( ug/ml). in the tb, the ri values for a ( ug/ml), b ( ug/ml), e (> ug/ml) and r ( ug/ml). each of the four anti-xa agents exhibit varying degrees of matrix independent anti-xa potencies in different systems, the collective order follows edoxaban > apixaban > betrixaban > rivaroxaban. andexanet alfa produced matrix dependent differential neutralization of the anti-xa effects of these agents. individualized dosing of andexanet alfa may be required to obtain desirable clinical results. the diagnostic and prognostic value of thromboelastogram (teg) in sepsis has not been determined. this study aimed to assess whether teg is an early predictor of coagulopathy [ , ] and is associated with mortality in patients with sepsis. in total, patients with sepsis on intensive care unit admission were prospectively evaluated. we measured teg and conventional coagulation tests(ccts)on preadmission and observed for development of , days and , , days respectively. multivariable logistic regression was utilized to determine odds of icu/hospital mortality. the parameter of teg (maximum amplitude, reaction time; ma/r ratio) was calculated to evaluate sepsis-induced coagulopathy. the admission patients were divided into three groupsma/r group(ma/r= - mm/min); ma/r group(ma/r> mm/min)and ma/r group(ma/r< mm/min). in our cohort of patients with severe sepsis, coagulopathy defined by ma/r ratio was associated with increased risk of icu/hospital mortality. introduction: blood sampling for coagulation assessment is often carried out in either arterial or venous samples in the intensive care unit (icu). there is controversy as to the accuracy of this method due to the inherent differences in physicochemical properties as well as the underlying effects of individual diseases in arterial and venous blood. clot microstructure has shown to be a new biomarker (fractal dimension-d f ) which encompasses the effects of diseases in all aspects of the coagulation system [ , ] . in this study, we compared the effect of all these factors in venous and arterial blood to see if there is a difference in the clot microstructure and quality. patients admitted to a tertiary intensive care unit and busy teaching hospital were recruited. arterial and venous blood was sampled from an arterial line and central venous catheter in situ from the same patient. standard markers of coagulation (pt, aptt, fibrinogen, full blood count), rotational thromboelastometry (rotem), whole blood impedance aggregometry and measured clot microstructure (d f ) were measured on both arterial and venous samples. no significant difference was observed in standard laboratory markers, rotem and platelet aggregation between arterial and venous blood. there were no differences in the fractal dimension (d f ) between the arterial and venous blood samples (d f . ± . vs . ± . respectively, p= . ). samples from patients with critical illness give comparable results from either arterial or venous blood despite their underlying pathophysiological process or treatment. this confirms blood for coagulation testing can be taken from arterial or venous blood. clinicians in the emergency setting use a wide range of hemostatic markers to diagnose and monitor disease and treatment. current methods rely on the anticoagulant effect of citrate on whole blood prior to laboratory analysis. despite the well-recognized modulatory effects of citrate on hemostasis, the use of anticoagulated blood has clear analytical advantages, including repeat sampling and storage. however by altering the physiological state of the blood reproducibility and accuracy of the test is affected. recent studies have shown the potential of a novel functional biomarker of clot formation: fractal dimension (d f ), that may give an improved diagnostic accuracy. in this study we assessed the potential of this new biomarker in scientifically measuring the effects of recalcification of citrated samples. methods: healthy volunteers were included. unadulterated and sodium citrate samples of blood were taken from each volunteer. citrated samples were recalcified using ( m cacl ). in the study we compared unadulterated whole blood d f results to citrated d f results and repeated the citrated d f experiments times for each sample over a hour period to ascertain reproducibility. the d f of citrated blood was significantly lower than that of unadulterated blood ( . ± . vs . ± . , p< . ). the results of the citrate samples when tested times over hrs gave a coefficient of variation of . %. for the first time we show that a functional biomarker of clot microstructure, d f , can precisely quantify and measure accurately the direct effect that the addition of the anticoagulant sodium citrate has on whole blood clot microstructure. the study also shows that the test is reproducible and has potential utility as a biomarker of acute disease in the emergency setting in citrated blood. this procedure now needs to be evaluated in a group of acute disease states. in this study, we analyzed the hematological abnormalities of dengue patients by thromboelastography (teg) at initial and -hour of fluid resuscitation. methods: this is a cross-sectional study evaluating teg readings of dengue patients with different severities presenting to the emergency department. laboratory confirmed dengue patient (positive ns antigen or igg/igm) was consecutively sampled. teg readings were taken at presentation and after -hour of fluid resuscitation. twenty dengue patients with varying severity had a median reaction time (r), α -angle, k time, maximum amplitude (ma) and lysis % (ly ) of . min, . ο , . min, . mm and . % respectively. mean fibrinogen was normal before and after fluid infusion. there is a non-significant reduction in ma with prolongation of other teg parameters between different dengue severities. there is a statistically significant reduction of α-angle and ma between pre and post -hour fluid resuscitation (p= . and p= . ). normal fibrinogen with low ma, which signifies a weak clot strength, may indicate either a platelet reduction, platelet dysfunction or both. reduction in ma and α-angle post fluid resuscitation is an alarming finding. this is in contrast with previous teg studies although none of it used normal saline exclusively, studied initial fluid resuscitation in emergency department settings or studied a subject with dengue. a bigger study, especially in severe dengue is needed to validate our findings. agreement between the thromboelastography reaction time parameter using fresh and citrated whole blood during extracorporeal membrane oxygenation with teg® and teg® s m panigada, s de falco, n bottino, p properzi, g grasselli, a pesenti fondazione irccs ca´granda ospedale maggiore policlinico, intensive care unit, milano, italy critical care , (suppl ):p the r (reaction time) parameter of kaolin-activated thromboelastography (teg) may be used to assess the degree of heparinization of blood during ecmo. a teg analysis is usually performed on two types of samples: fresh (f) or citrated-recalcified (c) whole blood. teg® can perform the analysis on c and f whole blood, the new teg® s (haemonetics corp., ma, usa) only on c whole blood. aim of the study was to compare the response of r to heparin using the two types of samples and two teg devices methods: during a three months period at fondazione irccs ca' granda -policlinico of milan, teg was performed (using teg ® and teg s® with and without heparinase, an enzyme that degrades heparin) on consecutive ecmo patients (as part of the gatra study, nct ) and in consecutive non-ecmo patients in whom a teg was requested for clinical purposes. bland altman analysis and lin's concordance correlation coefficient were used to assess agreement results: a total of paired samples were taken ( in-ecmo and off-ecmo). ecmo patients received . ( . - . ) iu/kg/h of heparin. among non-ecmo patients, of them did not receive any dose of heparin, two of them a very low prophylactic dose ( . and . iu/ kg/h, respectively), and one of them . iu/kg/h of heparin. using teg® , r was - . (- . ; . ) min shorter on c compared to f blood in patients receiving heparin (this difference disappeared using heparinase) and only - . (- . ; . ) min shorter in patients notreceiving heparin. r was - . (- . ; . ) min shorter using teg® s (which performs the analysis only on c blood) than teg® on f blood (figure ) . when evaluating the effect of heparin using teg, clinicians should be aware that results obtained using citrated-recalcified or fresh whole blood are not interchangeable. using citrated-recalcified blood to perform teg might lead to underestimation of the effect of heparin trauma patients are at high risk for venous thromboembolism (vte). the east guidelines recommend low molecular weight heparin (lmwh) for vte prevention and antixa monitoring after initiation of the medication or after adjusting doses in certain populations [ ] . studies have shown standard enoxaparin dosing of mg every hours may result in low antixa levels [ ] . this study aims to evaluate the efficacy of a pharmacist-lead protocol for adjusting enoxaparin dosing based on antixa levels in trauma patients. this single center retrospective chart review included adult trauma patients admitted from / / to / / . per protocol, patients with body mass index (bmi) ≤ kg/m were initiated on enoxaparin mg twice daily, and patients with bmi > kg/m were initiated on enoxaparin mg twice daily. peak antixa levels were drawn to hours after at least the third dose of enoxaparin with a goal therapeutic range of . - . iu/ml. the primary objective was time in days to goal peak antixa level. secondary objectives include vte occurrence, bleeding attributed to lmwh, and dosing regimens utilized. subgroups were analyzed based on body mass index (bmi). of patients identified, patients met inclusion criteria. median time to therapeutic antixa level was days (iqr - ). of patients fig. (abstract ) . agreement between teg® s and r teg® on citrated recalcified and fresh whole blood with bmi ≤ kg/m , patients ( . %) were dosed initially per protocol and / patients ( . %) met goal antixa level at first check (table ) . of patients with bmi > kg/m , patients ( . %) were dosed initially per protocol and / patients ( . %) met goal antixa level at first check. our results indicate the protocol is safe due to lack of bleeding attributed to enoxaparin, but less than % of patients achieved goal antixa level at first check. however, despite low rates of achieving goal antixa level, vte rates also remained low. introduction: most patients in the icu are given prophylactic anticoagulation with a fixed dose of mg once daily of enoxaparin (clexane) if cct is normal and mg if cct is low. studies on non icu patients have shown that afxa is below desired range for venous thromboembolism (vte) prevention. in the icu, many factors might influence afxa levels including weight, creatinine clearance (cct), shock and other medication. atxa activity was not yet reported in a big mixed icu population with variable morbidity. our study hypothesis is that enoxaparin is underdosed in most cases and routine afxa activity should be monitored in all icu patients. preventive enoxaparin ( mg qd) was given to all patients unless therapeutic dose was needed or contraindication existed. levels of afxa activity were taken hours after the rd dose. therapeutic vte preventive effect was defined as afxa activity of . - . . patient data was collected from medical files. the study is still ongoing, preliminary results were analyzed for patients. of patients ( %) had afxa activity below normal (subtherapeutic). weight and cct were negatively correlated with afxa activity (figure ). mean weight in the subtherapeutic afxa was significantly higher than the therapeutic group ( . vs. . respectively, p= . ). cct in the subtherapeutic afxa was significantly higher than the therapeutic group ( . vs. . respectively, p= . ). the normal cct group (> ) had significantly more patients with subtherapeutic afxa ( vs , p= . ). in our icu, % of the patients receive insufficient vte prophylaxis. overweight patients and patients with normal cct should probably receive higher enoxaprin dose. afxa activity should be routinely monitored in icu patients. in this study we use a new bedside biomarker to test its ability to measure anticoagulation effects on patients who present with acute first time deep vein thrombosis (dvt). dvt requires oral anticoagulants to prevent progression to potentially fatal pulmonary embolism and recurrence. therapeutic efficacy monitoring of direct oral anticoagulants (doac) including rivaroxaban is problematic as no reliable test is currently available. advances in hemorheological techniques have created a functional coagulation biomarker at the gel point (gp) which allows quantitative assessment of: time to the gel point (t gp ), fractal dimension (d f ) and elasticity (g') [ , ] . the prospective observational cohort study measured t gp , d f , g', standard coagulation and cellular markers in first time dvt patients at three sample points: pre-treatment and approximately and days following mg bd and mg od rivaroxaban respectively. strict inclusion and exclusion criteria applied. results: dvt patients (mean age years [sd± . ]; male, female) and non-dvt patients were well matched for age, gender and co-morbidities. mean t gp on admission was s (sd± . s) and . s (sd± . s) for dvt and non-dvt respectively. doac therapy significantly increased t gp to . s (sd± . s) after days, and subsequently increased to . s (sd± . s) at days as shown in table . d f , g' and standard hemostatic markers all remain within the normal range. conclusions: t gp demonstrates its utility in determining the anticoagulant effect of rivaroxaban. the significant difference in t gp between males and females needs further exploration. localized stasis as a result of transient provoking factors appears not to generate a systemic strength fig. (abstract p ) . correlation of anti factor xa activity with patient cct and weight. anti fxa activity value below . (red line), was considered "non-effective prevention" introduction: trauma remains the leading cause of death all over the world. to better exploit the trauma care system, precise diagnosis of the injury site and prompt control of bleeding are essential. here, we created a nursing protocol for initial medical care for trauma. the aim of this study was to evaluate the impact of protocoled nursing care for trauma on measures of quality performance. this was a retrospective historical control study, consisted of consecutive severe trauma patients (injury severity score > ). people were divided into two groups: protocoled group (from april to march ) and control group (from april to march ). we set the primary endpoint as mortality for bleeding. the secondary endpoints included time allotted from arrival to start of ct scan and surgery, administration rate of several drugs (sedations, painkillers, preoperative antibiotics, and tranexamic acid). for the statistical analysis, continuous variables were expressed as median (interquartile range) and were compared by wilcoxon rank sum tests given a nonnormal distribution of the data. we included patients in the study: in the control group before the introduction of the protocol, in the protocoled group. as a primary endpoint, the mortality for bleeding was similar between two groups ( % in the control group and % in the protocoled group). as a secondary endpoint, the time to ct initiation [group a ( - ) min vs group b ( - ) min; p < . ], and emergency procedure [group a ( - ) min vs group b ( - ); p < . ] were shortened by the protocol introduction. furthermore, the administration rates of sedations, painkillers, preoperative antibiotics, and tranexamic acid were increased in the protocoled group compared with the control group. although the mortality as a patient-oriented outcome was not affected, improved quality of medical care by nursing protocol introduction may be suggested in this analysis. this single-institutional prospective study included patients with uprf who were admitted to the trauma surgical intensive care unit (tsicu) and survived until discharge to home between and . we evaluated the activities of daily living after the discharge using physical and mental component scores of sf- ® and defined physical dysfunction (pd) as physical function (pf-n) score of or less. we divided the patients in the pd (n= ) and control (without pd, n= ) groups and compared the groups. the patients had experienced blunt injuries, including falls ( %) and pedestrian injuries ( %). the mean age was . years (men: . %); the median injury severity score was (interquartile range: - ); and the mean length of tsicu stay was . days. the average period from the injury until the survey was . months. there was no difference between the pd group and the control group in the patient characteristics, fracture type, pelvic fixation, and complications. at the time of the survey, the pd group had significantly more painful complaints than the control group (pd: . %, c: . %, p < . ), and had more physical and mental problems. the sf- ®subscale score showed a significant positive correlation between physical function and body pain, mental health respectively. the percentage of those who were able to return to work was not different in both groups (pd: . %, c: . %). in the multivariate analysis of pd, only age (odds ratio: . , % ci: . - . , p = . ) was relevant. long-term pd was observed in % of patients with uprf. the elderly were particularly prominent, and there was an association between pain and mental health. cells (rbc) this can lead to inhibition of oxygen transport function and development of hypoxia. currently used methods for analyzing the state of rbc either do not have sufficient accuracy or require lengthy analysis and expensive equipment. the use of a simpler and more informative electrochemical approach to assessing the state of rbc is very promising. electrochemical measurements in rbc suspensions (~ • cells / l) were carried out in a special electrochemical cell [ ] in the potentiodynamic mode in the potential range from - . to + . v using the ipc pro mf potentiostat (kronas, russia); optical measurements were performed using an eclipse ts inverted microscope (nikon, japan), a cfi s plan fluor elwd x / . lens (nikon, japan); rbc morphology was recorded in real time using a ds-fi digital camera (nikon, japan). when examining rbc of patients with severe multiple trauma a decrease in the ability of rbc to change their shape during electrochemical exposure was observed, indicating a decrease in deformability, which can lead to a disruption in the oxygen supply to tissues. at the same time, with the stabilization of the patient's condition a restoration of the ability of rbc to change morphology was detected which in turn could have a positive effect on the rheological characteristics of the blood (fig. ) . the results of the analysis of red blood cells using electrochemical changes in their morphology can be used as an additional method for the diagnosis of critical conditions. severe trauma should be treated immediately. whole-body ct (wbct) is widely accepted to improve the accuracy of detecting injuries. however, it remains the problem of time-consuming. therefore, we focused on the scout image taken in advance of wbct. detecting major traumatic injuries from a single scout image would reduce the time to start treatment. a previous study suggested that even specialists could not easily find chest and pelvic injuries using wbct scout image alone. in this study, we aimed to develop and validate deep neural network (dnn) models detecting pneumo/hemothorax and pelvic fracture from wbct scouts. we retrospectively collected anonymous wbct scouts together with their clinical reports at the osaka general medical center between january , , and december , . we excluded incomplete, younger than years old, postoperative, and poorly depicted images. the part of this dataset from january , , until december , , was used for validation and the rest for training dnn models. pneumo/hemothorax detection model and pelvic fracture detection model were trained respectively. accuracy, and areas under the receiver operating characteristic curves (aucs) were used to assess the models. the training dataset for pneumo/hemothorax contained images (mean age years; % female patients), and for pelvic fracture consisted of images ( years; %). the validation dataset for the former contained images ( years; %), and for the latter consisted of images ( years; %). the models achieved % accuracy and an auc of . for detecting pneumo/hemothorax, % and . for pelvic fracture. our results show that dnn models can potentially identify pneumo/ hemothorax and pelvic fracture from wbct scouts. increasing the number of samples, dnn model could accurately detect severe trauma injuries using wbct scout image. clinical information system (cis) is a computer system used in collecting, processing, and presenting data for patient care. it can reduce staff workload and errors; help in monitoring quality of care; track staff's compliance to care bundles; and provide data for research purpose. however, the transition from paper record format to electronic record involves changes in all kind of workflow in icu. therefore, an effective, efficient and evaluative rollout plan was required to minimize the risk that might arise from the new practice. methods: . small groups training were provided. a working station with different case scenarios were set up for practices. . individual tutorials were conducted to clarify questions. emphasis on patient care was always top priority. . contingency plans were available in case of server breakdown and power failure. downtime drills were conducted to prepare the staff in emergency situations. . step-by-step transition from paper record to electronic format was gradually carried out. a plan was discussed among cis team with clear dates and goals. . new items in cis were first reviewed and amended in team meeting until consensus was made; then were promulgated to all staffs during handover before implementation. fig. (abstract p ) . the effect of therapy on the electrochemically induced change in the morphology of red blood cells in patients with combined trauma . staff compliance and outcomes were then monitored; further review and amendment would be possible if necessary. cis roll-out plan was smooth. all staffs were able to integrate cis into the daily routine. the contingency plans were well acknowledged. new items were followed as planned. ongoing enhancement in cis was put forward on nursing orders, handover summary, and integration with inpatient medication order entry (ipmoe) system. with emerging benefits cis brings along, our staff has more time to devote to direct patient care. human input in data interpretation and clinical judgment on top of cis play an irreplaceable role in patient care. the daily request for laboratory tests in intensive care units is a common practice. although common, this strategy is not supported, since more than % of the exams requested with this rationale may be within the normal range [ ] . misconduct based on misleading results, anemia, delirium and unnecessary increase in costs may happen [ ] . we have developed a strategy to reduce laboratory tests without clinical rationale. observational retrospective study, from july to june . the number and type of laboratory orders requested, the epidemiological profile of hospitalized patients, the use of advanced supports, the average length of icu stay and the impact in outcomes such as mortality and hospital discharge at a private tertiary general hospital in the city of rio de janeiro / rj -brazil were analyzed. a strategy was implemented to reduce the request for exams considered unnecessary. approximately , patients underwent icu during this period. the epidemiological profile and severity of patients admitted to the unit were similar to those observed historically. there was a significant reduction (> %) in the request for laboratory tests and there was no negative impact on outcomes such as mortality, mean length of stay and no greater use of invasive resources. over the period evaluated, the estimated savings from reducing the need for unnecessary exams were approximately $ , per year. the rational use of resources in the icu should be increasingly prioritized and the request for routine laboratory tests reviewed. a strategy that avoids such waste, when properly implemented, enables proper care, reducing costs and ensuring quality without compromising safety. evaluating the medication reconciliation errors in icus after implementing a hospital-wide integrated electronic health record system a rosillette, r shulman, y jani university college hospital, centre for medicines optimisation research and education, london, united kingdom critical care , (suppl ):p introduction: medication errors in intensive care unit (icu) are frequent [ ] and can arise from a number of causes including transition of care. our aim was to investigate the impact of an integrated electronic health record system (ehrs) on medication reconciliation (mr) errors occurring at critical steps: during the transition from an icu to the hospital ward and from the ward to hospital discharge. the objective was to examine the influence of icu admission on long-term medication. we performed a monocentric study in icus of a university-affiliated hospital using drug chart and medical notes review to identify mr errors before, during and after icu admission. data were collected retrospectively from ehrs for consecutive patients discharged from the icu between june- july , and who were newly initiated on specific drugs of interest. results: drugs of interest were initiated in icu. many of these were continued after hospital discharge as shown in table . there was appropriate discontinuation of all the antipsychotics newly initiated in icu. other than anticoagulants, there was no reason documented for continuation of the initiated drugs. the planned durations were documented more often after hospital discharge than icu discharge for the following drug classes (% of patients with a plan after icu discharge to the ward; % after home discharge): antibiotics ( . %; . %), and steroids ( . %; . %), but less so for analgesics ( . %; . %), insomnia ( . %; . %), and gastroprotective drugs ( . %; . %). our study has shown that medications initiated in the icu can be inadvertently continued at icu and hospital discharge due to failure in documenting indication or duration. systems are required to deprescribe icu only drugs at discharge or communicate a plan for ongoing treatment. introduction: the surviving sepsis campaign advocates the use of care bundles to guide the management of sepsis and septic shock [ ] . our study aim was to assess compliance with a locally introduced sepsis pathway and to review intensive care unit admission outcomes. we carried out a prospective audit of patients admitted to the icu at royal surrey county hospital with a diagnosis of sepsis between / / and / / , assessing compliance with local sepsis bundle delivery, outcome of icu admission and degree of associated organ dysfunction. results: patients were identified, male ( . %), with a mean age of . ( - ). mean st hour sofa score on icu was . ( - ). % of patients required vasopressors, with % requiring noradrenaline > . mcg/kg/min, and % requiring an additional vasopressor/ inotrope. % required niv, % invasive ventilation and % rrt. icu mortality was %, in-hospital mortality %, mean icu stay days ( - ), and mean length of hospital stay days . in the presence of septic shock mortality was % with post-resuscitation lactate > , versus % in patients with no vasopressor requirement or lactate < (p< . ). the sepsis bundle was delivered in one hour to patients ( %). where the bundle wasn't completed, antibiotics were delayed in % of cases and blood cultures weren't taken in %. where the bundle was fully delivered, unit mortality was % vs. % where it was not (p< . ), but there was no significant difference in hospital mortality ( % vs. %, p> . ) or rates of vasopressor requirement, niv, ippv or rrt. there is room for improvement in timely delivery of the sepsis bundle in our hospital and various measures are being instituted. though there was no significant difference in hospital mortality, icu mortality was significantly lower in patients when the bundle was fully delivered. surviving sepsis campaign recommends h and h sepsis resuscitation bundle for sepsis. the study was done to assess the feasibility of the guideline and the compliance to sepsis- recommendations at an emergency department. prospective interventional study was conducted during one year. were involved in the study all sepsis cases with a qsofa ≥ . were assessed a composite of six components (measurement of serum lactate, obtaining blood culture before antibiotic administration and provision of broad-spectrum antibiotic before the end of h and provision of fluid bolus in hypotension, attainment of target central venous pressure assessed by cardiac ultrasonography, target lactate to normal level before the end of h ). time base line was the first medical contact at triage zone. secondary outcomes of study were the mortality rate and length of stay at intensive care unit (icu). were involved in the study, patients (mean age ± years, sex ration , ). pulmonary infections were the main cause of sepsis ( %) and urinary tracts infections ( %). at h components were achieved in % of cases [lactates ( %), blood culture ( %) and provision of antibiotics ( %)]. at h components were executed in % of cases (fluid provision achievement in %, ultrasonography assessment in % and normal lactate target achieved in %) (figure ). the reliability-adjusted rate for completion of the hours and hours bundle was at %. patients compliant to composite bundle got the mortality benefit (odds ratios = . , % [confidence interval, . - . ]). the study, however, did not show any benefits of mean intensive care unit (icu) length of stay. faisability of - h bundle ratio was at %. it has shown a significant improvement in adaptation and mortality benefit without reducing mean hospital/icu length of stay. more adapted procedures are needed to improve results targeting full compliance of patients to the - h bundle sepsis management. patterns and outcome of critical care admissions with sepsis in a resource limited setting m edirisooriya maddumage , y gunasekara , d priyankara national hospital of sri lanka, medical intensive care unit, colombo , sri lanka; sri jayawardenepura general hospital, department of critical care, nugegoda, sri lanka critical care , (suppl ):p introduction: paucity of epidemiological data is a major barrier in expansion of critical care services, especially in resource limited settings. we evaluated the patterns and the outcome of critically ill patients with sepsis admitted to a level medical intensive care unit in sri lanka. a retrospective cohort study was performed to describe the characteristics and outcome of patients with sepsis, admitted to a medical intensive care unit. sepsis is defined according to sepsis definition. we examined critically ill patients admitted over a period of months. sepsis was the commonest presentation, accounted for . % of all admissions. mean age was . ± . years. septic shock was present in . % on admission. pneumonia ( . %) was the commonest cause, while leptospirosis ( . %) and meningoencephalitis ( . %) accounted for fig. (abstract p ) . sepsis - h bundle components (% of goals achievment) second and third commonest causes of sepsis respectively. the sofa score on admission ( . ± . vs . ± . , p< . ), occurrence of aki ( % vs . %, p< . ) and the length of icu stay ( . days vs . days, p < . ), were significantly higher in sepsis than in patients without sepsis. icu mortality in sepsis (n= ) did not show a significant difference to nortality (n= ) in those without sepsis ( % vs %, p= . ). patients with leptospirosis had a mean sofa score of . , however the mortality ( . % vs %, p = . ) was similar to others with sepsis. in contrast, mortality related to sepsis was significantly high ( %, p< . ) in the packground of immunosuppression (n= ). respiratory failure secondary to pneumonia was the commonest cause of critical care admission with sepsis. sepsis related icu mortality was high in the background of immunosuppression. introduction: training in placement, and the subsequent safe confirmation of position, of a nasogastric (ng) tube, relies on clinicians completing an e-learning module at our trust. feeding through an incorrectly placed ng tube is a 'never event,' associated with significant morbidity and mortality [ ] . analysis of these incidents reveal that the misinterpretation of chest radiographs, by medical staff, who had not received competency-based training, is the most frequent cause [ ] . e-learning has revolutionized the delivery of medical education [ ] , however, there are barriers to its use [ ] . we hypothesized that, by taking e-learning content, and delivering it face-to-face, we would improve training rates, and thus patient safety. a questionnaire was completed by critical care doctors, concerning their knowledge of the existence of the e-learning module, whether they had completed formal training in ng tube placement, and how confident they were, on confirming correct positioning, using a point likert scale. all clinicians underwent training in the interpretation of ng placement, using chest radiographs. after the session they were asked to re-appraise how confident they felt. results were compared using paired t tests. confidence improved in all, rising from a pre-test average score of . (sd= . ), to post-session . (sd= . ), p=< . . prior to the intervention, % of the doctors were aware of the trust guidelines, but only % had completed the training. after the session, % were aware of the guidelines, and % had completed the training (figure ) . conclusions: e-learning is a useful tool, but has its limitations. by using course content, delivered with more traditional learning methods, we im-proved the number of appropriately trained clinicians, and thus the safe use of ng tubes in our unit. a systematic review of anticoagulation strategies for patients with atrial fibrillation in critical care a nelson, b johnston, a waite, i welters, g lemma university of liverpool, liverpool, united kingdom critical care , (suppl ):p there is a paucity of data assessing the impact on clinical outcomes of anticoagulation strategies for atrial fibrillation (af) in the critical care population. this review aims to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for atrial fibrillation. only studies contained analysable data. anticoagulated patients had a lower mortality at days and days post admission to critical care, however there was an increased incidence of major bleeding events compared to the non-anticoagulated population. thromboembolic events were comparable in both cohorts. data from current literature is scarce and inferences regarding the effectiveness of anticoagulation in patients in critical care with af requires further investigation and research. every new admission to the icu prompts a handover from the referring department to the icu staff. this step in the patient pathway provides an opportunity for information to be lost and for patient care to be compromised. mortality rates in intensive care have fallen over the last twenty years, however, % of patients admitted to an icu will die during their admission [ ] . communication errors contribute to approximately two-thirds of notable clinical incidents; over half of these are related to a handover [ ] . nice have concluded that structured handovers can result in reduced mortality, reduced length of hospital stay and improvements in senior clinical staff and nurse satisfaction [ ] . a checklist was created to review the information shared and to score the handover. this checklist was created with doctors and nurses and is relevant for handovers between all staff members. information was gathered prospectively by directly observing handovers on the icu. there is a notable discrepancy in the quality of handovers of new patients ( figure ). this is true of handovers between doctors, nurses and a combination of the two. it is also true of all staff grades. whilst a doctor may have reviewed the patient prior to their arrival, % (n= ) of patients weren't handed over to a doctor. the most commonly missed pieces of information were details of the patient's weight ( %, n= ), their height ( %, n= ), whether the patient has previously been admitted to an icu ( %, n= ) and whether the patient has any allergies ( %, n= ). the handover of new patients to the icu is often unstructured and important information is missed. this can be said for all staff members and grades, and for handovers from all hospital departments. post intensive care syndrome-family (pics-f) describes new or worsening psychological distress in family and caregivers after critical illness but remains poorly studied within specialist groups [ ] . we aim to define the degree of pics-f within our tertiary referral cardiothoracic centre and map change over the course of months. caregivers attended a -week multi-professional clinic alongside patients. peer support was facilitated through a café area and a caregiver group psychology session was offered with individual appointments if required. caregiver surveys were completed including: caregiver strain index; hospital anxiety and depression scale (hads); and insomnia severity index. patients also completed hads questionnaires. repeat surveys were completed at and months. results: over cohorts, caregivers attended, of which were spouses ( %), children ( %), and others ( %), with caregivers completing surveys at months. patients' median apache score was (iqr - . ) and median icu length of stay was days (iqr - . ). most admissions were from scheduled operations ( %). severe caregiver strain was present in / ( %) with changes to personal plans ( %) the most common sub category. hads demonstrated caregivers ( %) with anxiety and ( %) with depression. caregiver anxiety exceded that of patients', only reaching fig. (abstract p ) . each handover was scored according to the information accurately given to icu staff similar levels at months, while depression remained static ( figure ). median number of nights with 'bothered' sleep was (iqr - . ) and % of caregivers expressed problems with sleep. conclusions: significant psychological morbidity in caregivers from our tertiary cardiothoracic centre is in keeping with the general icu population [ ] . caregiver strain was reduced suggesting higher levels of resilience. future work should address mental wellbeing, particularly anxiety, to minimise the effects of pics-f. burnout syndrome is an illness that has increasingly affected health professionals. it is characterized by great emotional stress, physical and mental exhaustion and depersonalization of the individual. more serious cases can lead to job loss or even suicide. the described work identifies the burnout level of the multidisciplinary team through a specific questionnaireburnout syndrome is an illness that has increasingly affected health professionals. it is characterized by great emotional stress, physical and mental exhaustion and depersonalization of the individual. more serious cases can lead to job loss or even suicide. the described work identifies the burnout level of the multidisciplinary team through a specific questionnaire methods: application of a questionnaire suitable for the multidisciplinary group in november . the same was answered by professionals among physicians and nursing team. there was no identification of employees. after analysis of the results it is observed that % of the group presents initial burnout, % with the syndrome installed and about % with characteristics of greater severity. main factors found were: mental and physical exhaustion during the work day, the level of responsibility existing in the activity and the perception of disproportionate remuneration by work performed. all interviewees presented some degree of burnout or high risk to develop it. the most severe cases should be traced through occupational medicine and anti-stress measures with reorganization of work performance should be discussed in order to reduce the prevalence of this syndrome. introduction: burnout affecting the psychological and physical state of healthcare workers is recognized in the last years. burnout has been shown to affect the quality of care. whilst some risk factors have been identified, there are gaps within the literature related to mental health and burnout. the aim of this study is to measure levels of burnout across icu units in the metropolitan setting. to determine the level of burnout we used surveys, the maslach burnout inventory human services survey (mbi-hss) and the centre for epidemiologic studies depression scale (ces-d). with the mbi-hss we analysed different variables of burnout; exhaustion, cynicism and emotional exhaustion. basic demographic data and information regarding workout schedules were collected. we studied prevalence and contributing risk factors using and analysing the outcomes of the self-scoring questionnaires. analysis was performed using descriptive statistical analysis. there were respondents, % scored the threshold for depressive symptoms on the ces-d depression scale. interestingly, % (ci . - . %) of those meeting the score for depressive symptoms identified as having frequent restless sleep compared with % ( . - . %) from those not meeting. gender did not affect depressive symptoms % of females and % of males met the threshold. with the mbi-hss for exhaustion the mean was . (sd . ) which is a high level of exhaustion, the second variable cynicism the mean score was . (sd . ), which was considered high. the final variable was emotional exhaustion the mean was . (sd . ), this is considered moderate levels of emotional exhaustion. fig. (abstract p ) . hospital anxiety and depression scale (hads) scores for patients and caregivers at baseline, months, and months there was high prevalence of burnout in icu in all different categories as well as depressive symptoms. age and gender had no affect on burnout. interestingly, we identified that sleep and shift variables were linked to increased burnout. following the implementation of a fully integrated ehrs on march at our university-affiliated hospital we conducted a prospective study in icus by analysing pharmacists' contributions during data collection periods of days at , , and weeks post implementation. a pharmacists' contribution was defined as contacting the physician to make a recommendation in a change of therapy/ monitoring [ ] . the types of contribution were: a medication errorrectification of an error in the medication process; an optimizationproactive contribution that sought to enhance patient care, and a consult -reactive intervention in response to a request. a panel of experts composed of a senior pharmacist, a consultant, a nurse, and a pharmacy student assessed the impact of each contribution, scoring low impact, moderate impact or high impact. there were pharmacist contributions recorded in the periods. of these, ( . %) were medication errors, ( . %) were optimizations, and ( . %) was a consult ( table ) . % of the contributions were assessed as having medium impact, % as high impact and % as low impact. in general, the consultant assessed fewer contributions as having high impact compared to other members of the panel, with contributions assessed as high impact by the consultant versus by the senior pharmacist. implementing an ehrs in combination with contributions of clinical pharmacists can prevent medication related issues. interestingly the types of incident did not change over time. introduction: most icu's are noisy and may adversely affect patients outcomes and staff performance [ ] . who reports that the noise level in hospitals should not exceed db at daylight and db at night. the aim of this study is to evaluate the noise levels in intensive care unit, to apply awareness training to intensive care staff in terms of noise and to compare the noise levels before and after education. noise measurement areas are separated into points including patient bedsides, nurse desk, staff desk, wareroom, corridor and entrance of intensive care unite. measurements were performed times per day. after day, awareness training were given to staff in terms of harmful effects of noise. after the training, noise measurements were repeated during days. after total days the measurements were terminated. noise was measured with incubator analyzer (fluke model: bio-tek serial no: ). the mean noise values before and after the training were not statistically different from the mean average noise values (p> . ). when the time of measurement were compared, the noise levels were higher between - hours to other measurements before and after the training statistically (p= . ). seventeen different noise measurement areas were compared in terms of noise level, there was no statistically significant difference (p> . ). the differences were examined at the same hours between before and after training. contrary to expectations, noise levels were found to be higher after training statistically (p< . ). all of noise measurements were higher than the threshold values that who recommended. increased noise levels in critical care units may lead to harmful health effects for both patients and staff. our results suggest that much noise in the icu is largely attributable to environmental factors and behavior modifications due to education have not a meaningful effect. critical care medicine has focused on continuous, multidisciplinary care for patients with organ insufficiency in the face of lifethreatening illness. despite significant resource limitation low income countries carry a huge burden of critical illness. available data is insufficient to clearly show the burden and outcomes of intensive care units in these developing countries [ ] . the objective of our study is to evaluate the morbidity and outcomes of patients admitted to the intensive care unit of a tertiary university hospital in hawassa, ethiopia. this was a prospective observational study. data was registered and analysed starting from patient admission to discharge during a month period beginning september . data regarding demographics, sources of admission, diagnosis, length-of-stay and outcomes were analysed. the total number of patients admitted to the icu was , with patients dying over a one year period. the highest admission was from emergency medical unit, % and the lowest source was from pediatrics department, %. out of these, . % were males. the mean age was years ( - ). the most frequent aetiologies of morbidity in the admitted patients were traumatic brain injury ( . %), acute respiratory distress syndrome ( . %) and seizure disorder ( %). average median length of stay was . days (interquartile range: . - . ). the overall mortality rate was . %. the top four causes of death in the icu were respiratory illness at % followed by sepsis with multiorgan failure at %, trauma ( %) and central nervous system infection ( %). infection morbidity and mortality remains very high and needs institution of aggressive preventive strategies. the increase in frequency of trauma patients need to receive due attention. sepsis causes a high number of deaths, though overtaken by respiratory illnesses. improving the overall system of icu may achieve better outcomes in resource limited countries. introduction: icu mortality has been widely studied in the literature in relation to outcome index that primarily value organic failure [ ] . however, early mortality, in the first hours of admission has been little documented in the literature. the aim of this study is to analyze factors related to early mortality in icu. retrospective study at a second-level hospital. time of study was months. patients who died in icu were included, patients were classified according timing of dead, including those who died within the first hours of icu admission. the variables analyzed were age, sex, comorbidity, charlson index, apache ii, need for supportive treatments, more frequent admission diagnosis, origin and support treatment limitation decisions. the statistical study was carried out using the spss statistical program. patients were included during the study period, ( . %) died within the first hours of admission. no differences in the needs of support treatments were observed, more than % of patients received mechanical ventilation and vasoactive therapies. table shows characteristics of patients. half of icu deaths occur within the first hours of admission. severity at icu admisison was the main factor related with early mortality. severe stroke and coronary disease were the most frequent causes of early deaths in icu. in august the royal college of anaesthetists published guidelines on care of the critically ill woman in childbirth and enhanced maternal care [ ] . approximately babies are born across the area covered by leicester university hospitals that includes two large maternity units and is part of the uk ecmo network. this audit sets out to assess current practice and form a basis for future planning, which will likely be representative to most major obstetric centres. a retrospective audit of all patients admitted to 'intensive care units' in leicester over a month period following publication of the guidelines. the focus was on patients admitted to general adult intensive care and excludes all patients cared for in 'enhanced obstetric care' units. simple standards were proposed relating to accessibility, resuscitation, follow up and multi-disciplinary learning. in total women were identified with a broad range of diagnosis. the intensive care services are split across hospitals and we found this led to a number of problems. the presence of trained staff to resuscitate a newborn were easily accessible, no steps to provide necessary equipment pre-emptively were present in any centre. none of our critical care units had a plan for perimortem section. on-going reviews by the obstetric and midwifery teams were very variable. contact with the infant and breastfeeding support was also poor. despite the large number of deliveries significant work needs to be done in order to come in line with the new national guidelines for critically ill woman in childbirth. clearly defined pathways around escalation of care, resuscitation of both the mother and baby, integrating care of the mother and the infant in the first few days of life, and multidisciplinary learning events are being produced de novo in response to these guidelines, some of which will be illustrated in the associated poster. interprofessional collaboration scale [ ] . data were analyzed with ibm spss . results: it was found that cooperative attitudes with an average score of to are considered to be of average significance. interprofessional cooperation at an average score of , states that the level of cooperation is high and the quality of working life averages to , suggesting that it is very good. as far as professional satisfaction is concerned, nurses are happy, content and satisfied with their work, despite workload and burnout conclusions: interprofessional cooperation at the icu of the general hospital of larissa is high, but satisfaction from wages, resources, working environment and conditions is low. in addition, the results showed that improvements in hospital communication between staff, has a positive impact on the quality of professional life (table ) . contrasting with previous reports, decreased admissions per unit population in older and oldest age groups, and those with high comorbidity, suggest resource constraints may have influenced admission discussion and decision-making over the -year study period in wales. further investigation is warranted. icu discharge into weekends and public holidays: an observational study of mortality n mawhood, t campbell, s hollis-smith, k rooney bristol royal infirmary, general intensive care unit, bristol, united kingdom critical care , (suppl ):p introduction: up to a third of in-hospital deaths in icu patients occurs following ward stepdown [ ] . discharge time seems to be associated with in-hospital prognosis, but meta-analyses have not shown a difference in weekday compared to weekend discharge [ , ] . however, papers that examined discharge 'into' out-of-hours days, particularly on fridays, have found differences [ ] . our aim was to assess whether discharge from icu 'into' out-of-hours (ooh -weekends and public holidays) is associated with in-hospital mortality or re-admission to icu, and whether these patients were seen on the wards ooh by medical staff. all adults discharged from the general icu to a ward at the bristol royal infirmary in december - were included. in-hospital mortality rates were assessed for each day, with 'into weekdays' defined as sunday to thursday and 'into ooh' friday, saturday and the day before a public holiday. a subset of patients with data on readmission rate to icu was also examined. all available notes from patients discharged into ooh in were reviewed. the study included patients with a subset of with readmission data. sets of notes were reviewed from patients discharged into ooh (figure ). the in-hospital mortality was significantly higher in patients discharged into ooh ( . % vs . %, p= . ). within the subset, ooh was associated with in-hospital mortality or readmission to icu ( . % vs . %, p= . ), though readmission rate alone was not ( . % vs %, p= . ). of patients discharged into ooh, once on a ward % were reviewed by a specialty doctor but . % were not seen. this is the first study to examine icu discharge 'into' ooh days including public holidays. we found increased hospital mortality in ooh, similar to other studies [ ] . up to a fifth of high-risk icu stepdown patients were not reviewed by a doctor on ooh days. exploring the experiences of potential donors' family members (fm) in a follow up clinic is crucial to analyze the effects of organ procurement (op) on the bereavement process, to gain insight on the reasons of family refusals (fr), and to improve family care during op. a mixed-method study involving fm at and months after patients' death was developed and approved by local ethics committee. fm of potential donors after brain (dbd) and cardiac death (dcd) treated in careggi teaching hospital, florence (italy) were eligible if adult and consenting. invitation letters were sent to the entitled months after death and those who actively responded were involved in an encounter with a multidisciplinary group including a clinical psychologist, two nurses and two cultural anthropologists with expertise in op. organ replacement procedures such as ecmo (extracorporeal membrane oxygenation), lvad (left ventricular assist device) and dialysis are routinely used to treat multi-organ failure (mov). globally transplantation programs struggle with increasing organ shortage. patients (pts) with mov are a potential source for procurement. however, outcome data after kidney transplantation (ktx) from such donors are sparse. we retrospectively studied the cadaveric ktx at the charité berlin in and identified donors with ongoing organ replacement procedures. donor and recipient risk factors were assessed. overall patient and graft outcomes were analyzed at months post-transplant. a total of kidneys were transplanted. we identified ktx from donors with mov ( following cardio-pulmonary resuscitation, with acute renal failure - on dialysis) (figure ). in donors, a venoarterial ecmo was implanted during ecls-resuscitation. one donor needed a veno-venous ecmo due to ards, and donor had a lvad implanted due to cardiac failure. the donor age was ± . years (yrs). in addition, donors had at least one cardiac risk factor. the kidney donor risk index averaged . (sd ± . ) and s-creatinine prior to ktx was . (sd ± . one way to expand the potential donor pool is donation after circulatory death (dcd), and a strategy to reduce the complications related to the ischemic time is the use of normothermic regional perfusion (nrp) with extracorporeal membranous oxygenation (ecmo) [ , ] . we compare the use of standard nrp with an effective adsorption system inflammatory mediators (cytosorb®) in the regional normothermic reperfusion phase via regional ecmo, that involves a reduction in cellular oxidative damage, assessed as a reduction in levels of proinflammatory substances. we report a case series of dcd-maastricht iiia category donors, treated in ecmo with nrp, to maintain circulation before organ retrieval, in association with cytosorb® in patients. during perfusion, from starting nrp (t ), blood samples are collected times, every minutes (t , t , t ). during treatment with cytosorb®, lactate levels progressively decrease, ast and alt increase less than without cytosorb®, as sign of improvement in organs perfusion ( figure ). nrp with cytosorb® might help to successfully limit irreversible organ damages and improve transplantation outcome [ ] . development and implementation of uniform guidelines will be necessary to guarantee the clinical use of these donor pools. introduction: shock is a common complication of critical illness in patients in intensive care units (icus), who are undergoing major surgery. this condition is the most common cause of death in postsurgical icus. nowadays, there are different icu scoring systems for predicting the likelihood of mortality, such as apache or sofa. nevertheless, they are used rarely because they also depend on the reliability and predictions of physicians. in these sense, gene expression signatures can be used to evaluate the survival of patients with postsurgical shock. methods: mrna levels in the discovery cohort were evaluated by microarray to select the most differentially expressed genes (degs) between groups of those that survived and did not survive days after their operation. selected degs were evaluated by quantitative real time polymerase chain reactions (qpcr) for the validation cohort to determine the reliability of the expression data and compare their predictive capacity to that of established risk scales. introduction: this study evaluates the prognostic ability of frailty and comorbidity scores in patients with septic shock. the -day mortality rate of individual medical conditions are also compared. the burden of comorbid illness and frailty is increasing in the critical care patient population [ ] . outcomes from septic shock in patients with chronic ill-health is poorly understood. interstitial lung disease is a group of diseases associated with poor prognosis in the intensive care unit despite major improvement in respiratory care in the last decade. the aim of our study is to assess factors associated with hospital mortality in interstitial lung disease patients admitted in the intensive care unit and to investigate the long-term outcome of these patients. we performed a retrospective study in an intensive care unit of teaching hospital highly specialized in interstitial lung disease management between and . a total of interstitial lung disease patients were admitted in the intensive care unit during the study period. overall hospital mortality was %. two years after intensive care unit admission, / patients were still alive ( %). one hundred eight patients ( %) required invasive mechanical ventilation of whom % died in the hospital (figure ). acute exacerbation of interstitial lung disease was associated with hospital mortality (or= . [ . - . ] ), especially in case of acute exacerbation of idiopathic pulmonary fibrosis. multiorgan failure (invasive mechanical ventilation with vasopressor infusion and/or renal replacement therapy) was associated with very high hospital mortality ( / ; %). survival after intensive care unit stay of patients with interstitial lung disease is good enough for not denying them from invasive mechanical ventilation, except in case of acute exacerbation for idiopathic pulmonary fibrosis patients. if urgent lung transplantation or extracorporeal membrane oxygenation are ruled out, multiorgan failure should lead to consider withholding or withdrawal life support therapies. Αgi is a malfunctioning of the gi tract in icu patients associated with prolonged mechanical ventilation, enteral feeding failure and high mortality risk. the wgap of esicm proposed a grading system for agi. four grades of severity were identified: agi grade i, a selflimiting condition; agi grade ii (gi dysfunction), interventions are required to restore gi function; agi grade iii (gi failure); agi grade iv, gi failure that is immediately life threatening. the aim was to evaluate the feasibility of using agi grades i and ii as predictors of malnutrition and -year mortality in critically ill patients methods: single-center retrospective cohort study in a tertiary university hospital ( - ). agi grade iii and iv patients were excluded. Αnthropometric data, gi symptoms (vomiting,diarrhea), feeding intolerance, gastric residual volumes and abdominal hypertension were recorded. daily prescribed caloric intake was calculated using a standard protocol and daily achievement of caloric intake was recorded. mnutric score was calculated for all patients. a score ≤ was used to diagnose malnutrition. patients ( % men, mean age years) that stayed in the icu for > hours were included in the study. % were at high nutritional risk. -year mortality was %. the prevalence of agi ii was %. age, gender, bmi, mortality and energy intake did not differ significantly between patients with agi ii and those with agi i (table ) . logistic the study aimed to assess the effects of icu admission on frailty and activities of daily living in the ≥ 's population at -months. a prospective observational study with data used as a subset of the vip- trial [ ] . research ethics committee approval from the mater misercordiae university hospital (mmuh). inclusion criteria -≥ years of age and acute admission to icu from may to july . data collected on consecutive patients. frailty and activities of daily living (adl) were assessed using the clinical frailty score (cfs) and the katz index of independence in activities of daily living (katz). results: csf pre-admission frailty was present in % of patients, increasing to % at months ( figure ). % of survivors at -months had a cfs score increase by ≥ point. pre-frail and frail cfs patients suffered an average -point deterioration in their instrumental activities of daily living (iadl). % of katz patients were fully functional preadmission, deteriorating to % at months. % of patients declined by adl at months. % of the deceased were deemed fully functional initially. we demonstrate an association between an icu admission event and enduring functional decline at months. icu admission resulted in patients acquiring on average . new iadl limitations despite their initial cfs. this is echoed in a study by iwasyna et al. who also showed similar deteriorations in iadl and cognitive impairment [ ] . katz benefits may be best used in describing functional decline. % of patients developed at least one new limitation. however, the cfs takes into account iadl's and thus may be more sensitive in predicting the functional outcomes of an icu event at months. frailty: an independent factor in predicting length of stay for critically ill t chandler, r sarkar, a bowman, p hayden medway maritime hospital, critical care, gillingham, united kingdom critical care , (suppl ):p frailty has attracted attention in the healthcare community in recent years, as it is associated with worse outcomes and increased healthcare costs [ ] . our objective was to study the impact of frailty as recorded by clinical frailty scale(cfs) to prospectively evaluate the effect of frailty on hospital length of stay (los). a retrospective analysis of consecutively admitted critical care (cc) patients' data (jan' -oct' ) was performed. electronic health records were used to collect demographics, cfs and clinical outcomes. statistical analysis was performed using stata. students t-test, simple and multiple (adjusted for age, disease severity/icnarc score) linear regression were used for comparison between groups and to see group effect. we excluded extreme outliers (los> days; n= ). frailty was defined as cfs> . out of the patients (male %), ( %) were emergency admissions, the rest elective (table ) . ( %) were non-frail. the mean los were days (d) ± and d± (p< . ) in the frail and non-frail patients respectively. for emergency patients, los were d(± ) and d(± ) for the groups, (p< . ). for elective patients; los were d(± ) and los d(± ), (p= . ) for frail and nonfrail respectively. after adjusting, los was significantly higher in frail patients by days ( %ci , ; p< . ), by days ( %ci , ; p= . ) and by days ( %ci , ; p< . ) for total cohort, elective and emergency admissions respectively. the los was days higher in frail than non-frail (p< . ) for cc survivors. frailty was associated with significantly increased los in this cohort, independent of age and illness severity. hospital capacity planning should take this into consideration when modelling bed allocation fig. (abstract p ) . clinical frailty score -month trend robust clinical governance requires analysis of patient outcomes during an icu admission [ ] . on one adult icu weekly mortality meetings are used for this purpose and aid multidisciplinary reflections on individual patient deaths. however, such reviews run the risk of being subjective and fail to acknowledge themes which may relate to preceding or subsequent deaths. this paper describes a new mortality review process in which: a) reviews are structured using the structured judgement review (sjr) framework [ ] ; and b) themes are generated over an extended period of time to create longitudinal learning from death. the sjr framework has been developed by nhs improvement for the new medical examiner role, looking at inpatient deaths. we adapted this to better suit the icu creating a novel review structure. this involves explicit judgement comments being recorded, and the use of a scoring system to analyse the quality of care during the patient's stay with a focus on elements of care delivered on the icu. tabulation of this information allows analysis over time, identifying trends across all patients, and in specific subgroups. this framework has been rolled out at the st george's cardiothoracic icu weekly mortality meetings. themes that have emerged include parent team ownership, delayed palliative care referrals and inadequate documentation of mental capacity. this will continue as part of a three-month trial and following review of this trial may be extended to other critical care units in the trust. this system allows greater insight into patient deaths in a longitudinal fashion and facilitates local identification of problems at an early stage in a way that is not possible within the traditional mortality review format. the nature of the process means that key areas for change can be identified as a routine part of the clinical week. [ ] . in this study, we evaluated three distinct machine-learning methods for predicting possible patient deterioration after surgery. the data was collected retrospectively from the catharina hospital in eindhoven. this dataset contained all the surgeries conducted in the hospital from up to . the variables in this dataset were tested on their ability to differentiate between patients with a normal recovery versus patients with an unplanned icu admission after being admitted to the ward. the dataset contained variables related to either the preoperative screening, surgery or recovery room. all variables were tested for statistical significance using a univariate logistic regression (lr), from which a subset of statistically significant (p< . ) variables was created. these variables were used to train three different types of models, namely, the lr, support vector machine (svm) and bayesian network (bn). the network structure of the bn was designed using expert knowledge and the probabilities were inferred using the data. the three models were validated using five-fold cross-validation, resulting in the following areas under the receiver operating characteristic curve: . ( . - . ) for lr, . ( . - . ) for svm and . ( . - . ) for bn (fig. ) . the results indicate that machine learning is a promising tool for early prediction of patient deterioration. the bn was included because it permits incorporating clinical domain knowledge into the learning process. however, its performance resulted inferior to the lr and svm. in future work, we will investigate alternative domainaware methods, and compare the performance with that of the clinical experts. intensive care unit (icu) admission decisions of patients with a malignancy can be difficult as clinicians have concerns about unfavourable outcomes, such as mortality [ ] . a diagnosis of a malignancy is associated with an almost -fold increased likelihood of refusal of icu admission [ ] . recent large long-term mortality studies of patients with a malignancy admitted to the icu are scarce. therefore, our aim was to compare mortality of patients with either a hematological or a solid malignancy to the general icu population, all with an unplanned icu admission. all adult patients registered in a national intensive care evaluation registry with an unplanned icu admission from to were included. subsequently, we divided these patients into cohorts: cohort (all patients with a hematological malignancy), cohort (all patients with a solid malignancy), and cohort (a general icu population without malignancy). as primary outcome, we used -year mortality, and as secondary outcome, icu and hospital mortality. we included , ( . %) patients in cohort , , ( . %) patients in cohort and , ( . %) in cohort ( table ). the year mortality of patients of cohort , , and was . %, . % and . %, respectively (p< . ). age, comorbidities, organ failure, and type of admission (i.e. surgical or medical) were positively associated with -year mortality in all cohorts (p < . ). one-year mortality is higher in both patients with a hematological malignancy and patients with a solid malignancy compared to the general icu population. in addition, several factors were positively associated with -year mortality, i.e., age, comorbidities, medical icu admission, and organ failure. future research should focus on predictive modelling in order to identify patients with a malignancy that may benefit from icu admission. introduction: drug abuse is associated with immunosuppression in multiple mechanisms. despite that, the only study retrospectively reviewing drug abusers in the icu demonstrated less infections and better outcomes. we compared matched patient populations in order to fully understand whether drug abuse is a risk factor for infection and a predictor of poorer prognosis as is perceived by most physicians. we hypothesized that the drug abusers admitted to the icu will fare as good as or better than non-abuser icu patient populations. methods: this is a prospective study done between the years - on the entire patient population of the detroit medical center. after the drug abuse population was identified, controls were matched according to age and admission icu units. patients charts were reviewed and data regarding baseline demographics, infectious complication and outcome was extracted. data was retrospectively collected for drug abusers and matched controls. comorbidities and hospital admission diagnosis were significantly different between the two groups. disease severity scores were significantly higher in the drug abuser's patient group (dapg) on admission and during the icu stay. dapg had significantly more organ failure: more need for ventilation ( . % vs . % in the dapg (p< . )), more ards ( % vs . %, p= . ), more renal failure ( % vs . %, p= . ) and more need for renal replacement therapy ( . % vs . %, p< . ) .they had longer hospital length of stay (los). there was no difference in icu or hospital mortality. multivariable modeling did not find drug abuse to be an independent risk factor for hospital mortality, icu mortality (hosp: or = . , p = . ; icu: or= . , pp = . ), but was a risk factor for a longer hospital los (me= . , p < . ). drug abuse is not an independent risk factor for mortality or icu los. drug abusers should be evaluated like other patients based on baseline comorbidities and disease severity. this is a small audit which although it did not include general icu still reflects the need for encouraging clinicians and patients to speak freely regarding escalation plans. medical decsions is clinician led however this audit was carried by nursing staff as we have a duty to be advocate for our patients involvement in medical care [ ] . a retrospective analysis of independent risk factors of late death in septic shock survivors c sivakorn , c permpikul , s tongyoo (fig. ) . the pap and katz scales seem to be adequate for predicting mortality of critically ill patients admitted to a medical icu. this finding may help in the elaboration of future icu mortality scoring systems, as well as in more rational use of resources. however, further multicenter studies are needed to better elucidate these results. adherence this last group was chosen because of its experience and specific training in the field of bioethics as a control group or reference. a total of respondents participated in the study. . % were emergency physicians, . % intensivists, . % emergency nursing, . % icu nursing, . % resident doctors, . % medical students and . % other professions. we observed variability in the responses observed not only between different groups of professionals but even within the same group reflecting the difficulty in decision making. variability was observed regarding decisions in end of life ethics conflicts. a high degree of similarity with the group of master in bioethics was observed in the responses issued by medicine students. the barriers and facilitators to framing goals of patient care (gopc) and factors motivating decision making is relatively unexplored [ , , ] . a three part survey of physicians at an australian hospital in a culturally and linguistically diverse suburb ( table ) . identification of levels of confidence and barriers and facilitators to gopc discussion and decision making was the main outcome measure. factors influencing decision-making was analysed through scenarios. results: out of eligible participants responded; female, male, clinical experience - years. level of confidence was ranked between "somewhat confident and very confident." all but one respondent had six months of icu experience. no differences in the level of confidence among physician groups. barriers and facilitators were identified; poor prognosis and patient or family request were most common facilitators; conflict between treating teams and the patient/surrogate and language barriers were most common barriers. factors driving gopc decision-making included clinical, value judgement, communication, prognostication, justice and avoidance. numerous barriers and facilitators were identified. factors driving decision making did not just consider clinical factors; conflict and we aimed to investigate physician-related factors contributing to individual variability in end-of-life (eol) decision-making in the intensive care unit (icu). qualitative study with semi-structured interviews with specialists in critical care, (experience - years) from swedish icus. data was analyzed in accordance to principles of thematic analyses. most of the respondents felt that the intensivist's personality played a major role in eol decisions (table ) . individual variability was considered inevitable. views on acceptable outcome: respondents experienced that the possible outcome for patients was interpreted very differently and subjectively among colleagues, and what seemed an acceptable patient-outcome for one doctor, was not acceptable for another. values: most of the respondents were well aware that they might be affected by their own values and attitudes in the decision-making process. interestingly, several respondents mentioned that they thought that patients that were marginalized by society, especially drug-abusers could be at risk for receiving decisions to limit life sustaining treatments (lst) more often than others. none of the respondents thought that their own religious beliefs played any part in decision making. fear of criticism: among the less experienced respondents there was a clear sense of fear of making a questionable assessment of the patient's medical prognosis. there was a fear for criticism from colleagues that were not directly involved in the decision-making, and may have made another decision. this created a wish among younger respondents to defer or avoid participating in decision-making. physician-related, individual variability in eol decisions primarily consisted of differing views on acceptable outcome, values and fear of criticism. can (figure ). within each quartile of sofa score, mortality was highest in patients with pneumonia and peritonitis and lowest in patients with cellulitis (see figure ). the sepsis- consensus definition identified organ dysfunction as the hallmark feature of sepsis [ ] . in developing sepsis- , the sequential organ failure assessment (sofa) score was chosen for its prognostic value and relative ease of implementation clinically [ ] . we propose an update based on epidemiologic data from two intensive care databases that more effectively captures organ dysfunction in the context of sepsis- . using the mimic-iii (exploration) and e-icu (validation) databases, we extracted patients with suspicion of infection to form the study cohort. the predictive power of each sofa component was assessed using the area under the curve (auc) for in-hospital mortality. a logistic model with the lasso penalty was used to find an alternative statistically optimal score. results: by utilising alternate markers of organ dysfunction (e.g. lactate, ph, urea nitrogen) we demonstrated a significant improvement in auc for several versions of the new score, sofa . ( figure ). the sofa score can be updated to reflect current advances in clinical practice. using epidemiologic data, we have shown that substitution of existing components with more powerful measures of organ dysfunction may provide an improved score with greater predictive power. moreover, sofa . exhibits equivalent ease of implementation, but better reflects organ dysfunction in the context of sepsis- . introduction: risk of acute organ failure (aof) in cancer patients(pts) on systemic cancer treatment isunknown. however, % of non-hematologic and % of hematologic cancer pts will need admission to intensive care unit (icu). ipop-sci- / is a prospective cohort study designed to ascertain the cumulative incidence of aof in adult cancer pts. single centre prospective cohort study with consecutive sampling of adult cancer pts admitted for unscheduled inpatient care while on, or up to weeks after, systemic cancer treatment. primary endpoint was aof as defined by quick sofa. six months accrual expected an accrual of pts to infera population risk aof with a standard error of %. between / and / pts were on systemic anticancer treatment, had unscheduled inpatient care and were eligible for inclusion and were included. median age was years, % were male, % had adjusted charlson comorbidity index (cci) &gt; and hematologic cancers accounted for % of pts. the cumulative risk of aof on hospital admission was % ( %ci: - ); and of aof during hospital stay was % ( %ci: - ). aof was associated with older age, cci &gt; ,hematologic malignancy, shorter median time from diagnosis and &gt; prior line of therapy. on admission, % of pts were considered not eligible for artificial organ replacement therapy (noaort) and % of pts who developed aof while inhospital were judged noaort. overall, ( %) of aof pts wereadmitted to icu, . % for aort. median follow up . months (min ; max ). inpatient mortalitywas %, with icu mortality rate of %, with median cohort survival . months ( %ci: . - . ). on multivariate analysis, aof was an independent poor prognostic factor (hr . ; %ci . - . ). risk of aof in cancer pts admitted for unscheduled inpatient care while on systemictreatment is %, and risk of icu is %. aof in cancer pts was an independent poor prognostic factor. a severity-of-illness score in patients with tuberculosis requiring intensive care u lalla, e irusen, b allwood, j taljaard, c koegelenberg tygerberg academic hospital, internal medicine, division of pulmonology and icu, cape town, south africa critical care , (suppl ):p we previously retrospectively validated a -point severity-of-illness score aimed at identifying patients at risk of dying of tuberculosis (tb) in the intensive care unit (icu). parameters included septic shock, human immunodeficiency virus with cd < /mm , renal dysfunction, ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (pao :fio ) < mmhg, diffuse parenchymal infiltrates and no tb treatment on admission. the aim of this study was to validate and refine the severity-of-illness score in patients with tuberculosis requiring intensive care. we performed a prospective observational study with a planned post-hoc retrospective analysis, enrolling all adult patients with confirmed tb admitted to the medical intensive care unit from february to july . descriptive statistics and chi-square or fisher's exact tests were performed on dichotomous categorical variables, and t-tests on continuous data. patients were categorized as hospital survivors or non-survivors. the -point score and the refined -point score were calculated from data obtained on icu admission. results: forty-one of patients ( . %) died. the -point scores of nonsurvivors were higher ( . +/- . vs . +/- . ; p= . ). a score ≥ vs. < was associated with increased mortality ( . % vs. . %; or . ; %ci, . - . ; p= . )( table ) . post-hoc, a pao :fio < mmhg and no tb treatment on admission failed to predict mortality whereas any immunosuppression did. a revised -point score (septic shock, any immunosuppression, acute kidney injury and lack of lobar consolidation) demonstrated higher scores in non-survivors ( . +/- . vs. . +/- . ; p< . ). a score ≥ vs. ≤ was associated with a higher mortality ( . % vs. . %; or . ; %ci, . - . ; p< . ) ( table ) . the -point severity-of-illness score identified patients at higher risk of death. we were able to derive and retrospectively validate a simplified -point score with a superior predictive power. chronic critical illness remains a scientific challenge, from its conceptualization to its impact on patient prognosis [ ] . we evaluated the long-term evolution of icu survivors by identifying the real burden of prolonged critical illness on survival, quality of life and hospital readmissions. we conducted a prospective cohort in brazilian hospitals including icu survivors with an icu stay > h. we compared the patients diagnosed with chronic critical illness with the other patients. telephone follow-up at and months. quality of life was measured by the sf- questionnaire. it was observed that % of patients had some definition of chronic critical illness. chronic critically ill patients had higher mortality at months (p= . ). this difference is mainly due to higher intrahospital mortality (p= . ). mortality after hospital discharge was similar between groups. there was no difference in hospital readmission rate at months. various scores are developed to predict pulmonary complications such as ariscat for patients at-risk of postoperative pulmonary complication [ ] and lips for patients at-risk of lung injury [ ] . the aim of this study was to compare these scores with ours for predicting pulmonary complications in mechanically ventilated patients in sicu. this prospective observational study was conducted in sicu at a university hospital. adult patients admitted to sicu and required mechanical ventilation > hours were included. primary endpoint was the composite of pulmonary complications including pneumonia, ards, atelectasis, reintubation, and tracheostomy. multivariate analysis was performed to identify risk factors of pulmonary complications and the predictive score was developed. the roc analysis was performed to compare power of ariscat, lips and our newly developed score for predicting pulmonary complications. outcomes in intensive care units have been reported to be better in higher-volume units [ , ] . we compared outcomes for high-risk patients between low and higher volume units. audit data from irish icus is analysed and reported by the intensive care national audit & research centre (icnarc) in london. icnarc report risk-adjusted mortality rates in all patients and in low-risk patients(predicted mortality rate < %) for each unit, using the icnarch- model to predict the risk of death. we used this data to calculate the proportion of high-risk patients(predicted mortality > %) in each unit, the mortality rate for high-risk patients, the riskadjusted mortality rate and we compared the overall risk-adjusted mortality between low and high volume units. the median number of annual new-patient admissions among participating units was ; units below this were defined as lowvolume and those above as high-volume units. the proportion of all admissions to each unit who were high-risk ranged from % to %(mean %). unit mortality rates for high-risk patients ranged from % to %. the ratio of observed to expected mortality(standardized mortality ratio -smr) for high risk admissions in each unit ranged from . to . (mean . ). in fig. introduction: adl weakening is often seen after intensive care and called postintensive-care syndrome (pics). this is also seen in even outside icu and proposed to be called post-acute-care syndrome (pacs), especially in elderly patients. in patients with infection, sofa score is famous for predicting in-hospital mortality, but there are no tools for predicting adl weakening during admission. to search for risk factors for adl weakening during admission other than the age, we conducted a retrospective observational study. the subjects were surviving patients with infection, aged from to who were admitted to our department from april , to may , . information of basic characteristics, laboratory data on admission and adjunctive therapies were extracted from our database. we use barthel index (bi) as adl evaluation, and the bi at discharge were evaluated by nurses. we stratified patients by bi at discharge of over or not, and investigated factors that predicted it. we compared each factor between groups, and perform a logistic regression analysis with those that had a significant effect clinically or statistically. despite improved outcomes of intensive care unit (icu) patients, sleep deprivation remains a major concern after icu discharge. multifaceted causes make it difficult to treat and understand [ ] . not many studies have explored sleep deprivation beyond icu. this is evidenced by findings from a recent systematic review [ ] which included studies with only one study [ ] reporting sleep deprivation beyond icu. the aim of this paper is to present findings of sleep deprivation beyond icu from a larger study that examined the experience of critical illness in icu and beyond in the context of daily sedation interruption. hermeneutic phenomenology was used to conduct the study. participants aged years and above who fulfilled the enrolment criteria were enrolled into the study. the cohort comprised male and female participants. in-depth face to face interviews at two weeks after discharge were conducted and repeated at six to eleven months. interviews were audio taped, transcribed and thematically analysed. significant statements were highlighted and categorized for emergent themes. six participants continued to experience sleep deprivation up to eleven months after icu. two cited dreams about icu, three could not explain why they continued to fail to sleep and one stated that he continued hearing icu alarms in the silence of the night. sleep deprivation continues beyond icu due to nightmares, delusional memories and unexplained reasons. further research is needed to establish causes of sleep deprivation and explore ways to promote sleep in critical illness survivors after icu discharge. frailty is being increasingly seen as an independent syndrome. frail patients now account for an increasing proportion of hospital and critical care admissions [ ] . we aimed to compare frailty and mortality in our intensive care unit. clinical frailty score (cfs) was incorporated within the electronic health record (ehr) . we performed this retrospective analysis on the data collected between jan' and oct' . the predictor and outcome for this study were frailty and hospital mortality respectively. all demographic data, acute physiology score, critical care and hospital outcome data were automatically collected in the ehr and recorded. we used a cut off of cfs> and above to define non-frail and frail respectively. chi-squared test, simple and multiple logistic regression were used. adjustment was done for icnarc score and age. total number of patients was , of which ( . %) died in hospital. within the patients< years (n= ), ( %) were recorded as frail or vulnerable. the number of elective and emergency admission were ( %) and ( %) respectively. in the frail and nonfrail, mortality rates were % and . % (p< . ) respectively, with odds ratio of . ( % ci . , ; p< . ) ( age is a well-known risk factor for critical care (cc) outcome and is incorporated into many prognostic tools; however, this has been criticized for assumption of normal physiology for young at baseline. in recent years, frailty in cc prognostication has been of interest, with meta-analysis correlating worsening outcomes with increasing frailty [ ] . in this study, we compared the effect of frailty versus age for determining hospital survival for critically ill patients. we conducted a prospective cohort in brazilian hospitals including survivors of an icu stay > h. we compared chronic critically ill patients (icu stay> days) and the other patients. we performed psychological and functional presential assessment in patients within hours of icu discharge and by telephone at and months. the prevalence of chronic critically ill patients was %. regarding outcomes, chronic critically ill patients had a higher incidence of depressive symptoms than other patients in the immediate post-icu discharge (p = . ), as well as a higher incidence of muscle weakness (p < . ). however, in subsequent evaluations, we found no difference between groups regarding psychological symptoms -depression, anxiety and post-traumatic stress. higher functional dependence was observed in critically ill patients, but without difference in the quality of life score, both in the physical (p = . ) and mental (p = . ) domains. chronic critically ill patients, when compared to patients with stay> h, have a higher incidence of depressive symptoms at icu discharge. this difference disappears in the follow up. chronic critically ill patients present higher levels of functional dependence but without repercussions on quality of life scores. introduction: activation of the inflammatory response after cardiac arrest (ca) is a welldocumented phenomenon that may lead to multi-organ failure and death. we hypothesized that white blood cell count (wbc), one marker of inflammation, is associated with one-year mortality in icu treated ca patients. we used a nationwide registry with data from five academic icus to identify adult ca patients treated between january st and december st . we evaluated the association between the most abnormal wbc within hours of hospital admission and one-year mortality. we accounted for baseline risk of death using multivariable logistic regression (adjusted for age, gender and h sequential organ failure assessment [sofa] score). a total of , patients were included in the analysis. of those patients , ( %) were alive one year after ca. we plotted wbc against baseline risk of death and through graphic examination of a locally weighted scatterplot smoothing (lowess) curve found the lowest risk of death to be associated with a wbc of (e /l) ( figure mrps were identified by a specialist icu pharmacist during this programme and classified by their significance on a scale of one to four. logistic regression was used to determine if demographic factors were associated with the occurrence of a clinically significant mrp -a significance score of two or above (figure ) . the adjusted model included age, icu los, hospital los, apache ii, number of days of renal replacement therapy, number of days of ventilation, the number of medications prescribed at icu discharge, and the who analgesia classification at ins:pire. there were increased odds of having a clinically significant mrp for hospital los (or results: · % (n= ) of patients required at least one pharmacy intervention. the median number of interventions required per patient was one (iqr - ); the maximum number was six. mrps were recorded in this cohort. the most common intervention was clarifying duration of treatment (n= ), followed by education (n= ), and correcting drug omissions (n= ). the bnf drug class most frequently associated with mrps was neurological (n= ), which comprises analgesics (n= ) and psychiatric medications (n= ) ( figure ). this was followed by cardiovascular medications (n= ), gastrointestinal medications (n= ), nutritional medications (n= ), and others (n= ). many icu survivors experience mrps. the most common class of mrp was neurological, reflecting the high incidence of chronic pain and psychiatric illness in this population following discussion with icu staff, ward staff and fy doctors, a formal standardized handover system was introduced. this involved a verbal handover to the appropriate fy by an icu doctor and the patient drug chart to be rewritten in icu at the time of handover. the next change was to display posters on the wards to alert staff that the medical team are to be contacted when a patient comes to the ward from icu and to ensure the drug chart is completed. the baseline data showed a median time delay of hours, with one patient waiting hours for a drug chart. following the interventions the median time delay has decreased to hours within months as demonstrated in figure . the changes have received positive feedback from icu staff, ward staff and fy doctors. the aim of reducing the time delay by % has been achieved with the median time delay now hours. this has improved patient safety by significantly reduced delays in medications and through the introduction of a standardized handover. this has also provided an opportunity for junior doctors on the wards to seek clarification regarding medications and the clinical management plan for the patient. this has established a communication channel between icu and the wards making patient care safer and more effective. telemonitoring outside the icu is scarce. but with innovative wearables measuring respiratory and heart rate wirelessly, culture on intrahospital telemonitoring should definitely change. however, culture has been known to be one of the most crucial success factors in innovation, especially in health care. human design thinking is a promising tool in health care innovation but rarely used in a multidisciplinary team to initiate an innovation culture and stimulate sustainable collaboration. the aim of this study was to initiate a pilot project with a multidisciplinary team to start using wearables for early warning score (ews) on a clinical ward. human design thinking was used to write a value proposition on wearables in clinically admitted neutropenic hematologic patients in an academic center. a multidisciplinary team was performed to cover all disciplines involved in the technical, clinical and administrative parts of the project. a vendor was chosen based on its product specifications in relation to the present hospital monitoring infrastructure. in design thinking sessions, critical appraisal of multiple telemonitoring factors was performed by sub teams and a canvas projectplan was constructed. the project team was formed of registered nurses, physicians, itspecialists, electronic health record consultants; a critical care physician was appointed as project leader. the main critical factors were: unseamlessly transmitting of both heart and respiratory rates including appropriate movements filtering to the nurse's smartphones direct uploading into electronic health record with automated ews calculation nurse driven protocol on ews follow up. philips healthcare with their intellivue guardian wearable biosensor was the chosen vendor ( figure ). design thinking in a multidisciplinary health care team could positively influence the innovation culture. scientific evaluation of this wearable will focus on both nurse's acceptance and data storage and is expected in the summer of . severity, readmission and lengh of stay were lower in patients receiving discharges directly to home. it seems like a safe way to discharge low-risk short stay patients. it seems to save resources and reduce costs, as well as the need for hospital beds. however, futher estudies are needed to actualy evaluate this safety. forty-four cultures were analyzed with eplex ( figure ). complete agreement with conventional diagnostics was observed in / cases. no false-positive results were observed, yielding a sensitivity and specificity of % and % respectively for target pathogens. time to result was, on average, . h faster with eplex compared to conventional diagnostics. antimicrobial therapy could have been optimized in patients based on the eplex result, but treatment was only changed in one case (e.coli ctx-m+) receiving meropenem . h before the antibiogram was available. the eplex blood culture panels provide high accuracy and significantly faster results. the current implementation offers substantial potential value at a minimal cost, and is a feasible approach to -h/ days blood culture diagnostics in many hospital settings. however, efforts to increase adherence are needed. the rapid increase of extended spectrum β-lactamases (esbl)-producing pathogens worldwide makes it difficult to choose appropriate antibiotics in patients with gram-negative bacterial infection. cica-beta reagent (kanto chemical, tokyo, japan) is a chromogenic test to detect beta-lactamases such as esbl from bacterial colonies. the purpose of the study was to reveal whether cica-beta reagent could detect esbl-producing pathogens directly from urine rather than bacterial colonies to make a rapid bedside diagnosis of the antibiotic susceptibility of gramnegative pathogens. we conducted a prospective observational study from july to october . patients were eligible if they were performed urinary culture tests and gram negative pathogens were detected at least + from their urine samples. the urine sample was centrifugated at x g for min. the supernatant of sample was re-centrifugated at x g for min and the pellet was mixed with cica-beta reagent. the test was considered positive when the enzymatic reaction turned from yellow to red or orange. (fig. ) . the bundle approach could be an effective strategy to prevent hospital-acquisition of drug-resistant pathogens in icus. fig. in the aspect-np trial, c/t was noninferior to mem for the treatment of habp/vabp. we evaluated outcomes from that study in the subgroup of pts failing current antibacterial therapy for habp/vabp at enrollment. methods: aspect-np was a randomized, controlled, double-blind, phase trial in which mechanically ventilated pts with habp/vabp received g c/t or g mem every h for - days. pts with > h of active gram-negative antibacterial therapy within h prior to first dose of study therapy were excluded, except those pts failing current treatment (i.e. signs/symptoms of the current habp/vabp were persisting/worsening despite ≥ h of antibiotic treatment). primary and key secondary endpoints, respectively, were -day all-cause mortality (acm) and clinical response at test of cure (toc; - days after end of therapy) in the intent to treat (itt) population. pts failing current antibacterial therapy for habp/vabp were prospectively categorized as a clinically relevant subgroup. at baseline, failing current therapy for habp/vabp was reported in / ( %) c/t and / ( %) mem itt pts, mostly piperacillin/ tazobactam ( %), rd/ th-generation cephalosporins ( %), fluoroquinolones ( %), and aminoglycosides ( %). baseline demographic and clinical characteristics in this subgroup, including prior therapy regimen, were generally similar between treatment arms. there were greater proportions of patients with esbl+ enterobacterales ( %) and pseudomonas aeruginosa ( %) in the c/t arm than the mem arm ( % and %, respectively). lower -day acm was seen with c/t than mem, as evidenced by % confidence intervals for treatment differences that excluded zero ( figure ); statistical significance cannot be assumed because subgroup analyses in this study were not corrected for multiplicity. conclusions: c/t was an effective treatment for habp/vabp pts who had failed initial therapy. catheter-related blood stream infection (crbsi) is common serious infections and associated with increased mortality in intensive care units (icu). one of the most important strategy to prevent crbsi is to minimize the duration of central venous catheterization. we built a medical team consisting of doctors, nurses and pharmacists in icu to discuss whether patients needed central venous catheter (cvc) in terms of monitoring hemodynamics and administering drugs, and recommend catheter removal to attending physicians every day in april . the purpose of this study is to evaluate whether our team-based approach could shorten the total duration of catheterization and reduce crbsi. this was a retrospective historical control study conducted from april to october in the icu of a tertiary care hospital in japan. every patient admitted to the icu during the study period was eligible if they were inserted cvc. patients were divided into groups: conventional (from april to march ) or intervention (from april to october ). we set the primary endpoint as onset of crbsi. the secondary endpoints included the duration of central venous catheterization, the length of icu stay and hospital mortality. crbsi was defined as bloodstream infection in patients with cvc, not related to another site. we included patients: in the conventional group and in the intervention group. the reduced, though nonsignificant, tendency of crbsi was observed in the intervention group [hazard ratio, . ( % confidence interval, . - . ; p = . )]. the intervention group was significantly associated with reduced duration of central venous catheterization ( days vs days; p < . ). no difference was observed in the length of icu stay and in-hospital mortality between groups. the team-based approach to assess cvc necessity could shorten the duration of central venous catheterization and might reduce crbsi. introduction: empiric antibiotic therapy decisions are based upon a combined prediction of infecting pathogen and local antibiotic susceptibility, adapted to patients' characteristics. the objective of this study was to describe the pathogen predominance and to evaluate the probability of covering the most common gram-negative pathogens in icu patients with respiratory infections. methods: data were collected from multiple us and european hospitals as part of the smart surveillance program ( ). mic (mg/l) testing was performed by broth microdilution, with susceptibility defined as follows for p. aeruginosa & enterobacterales: ceftolozane/tazobactam results: hospitals from countries provided gram-negative respiratory isolates from patients located in an icu in the us ( %), eastern europe ( %) and western europe ( %) in . the most common pathogens isolated were p. aeruginosa ( %), k. pneumoniae ( %), e. coli ( %), and a. baumannii ( %). among enterobacterales, % ( / ) were esbl positive. figure provides the probability of covering the most common respiratory gram-negative pathogens from icu patients. co-resistance between commonly prescribed first line β-lactam antibiotics is common: when nonsusceptibility (ns) of one agent was present, susceptibility to other βlactams was generally < %. ceftolozane/tazobactam provided the most reliable in vitro activity in both empiric and adjustment prescribing scenarios compared to other β-lactam antibiotics. ceftolozane/tazobactam ensured a wide coverage of the most common gram-negative respiratory pathogens demonstrating high susceptibility levels and provided the most reliable in vitro activity in both empiric and adjustment antibiotic prescribing scenarios. further studies are needed to define the clinical benefits that may translate from these findings. evaluation of compliance of icu staff for vap prevention strategies on the outcome of patients a kaur fortis hospital, critical care, mohali, india critical care , (suppl ):p ventilator-associated pneumonia is the most common nosocomial infection diagnosed in adult critical care units. it is associated with prolonged duration of mechanical ventilation, increased icu stay and increased mortality. it continues to be a major challenge to the critical care physicians despite advances in diagnostic and treatment modalities. the primary objective of the study was to determine the compliance of icu staff towards vap prevention bundle and secondary objective was to determine the incidence, risk factors and outcome of vap patients. single center, prospective, observational study carried out from february to july . patients mechanically ventilated for more than hours and satisfying the inclusion and exclusion criteria were enrolled in the study. vap was diagnosed using the cdc criteria and clinical pulmonary infection score. vap preventive strategies were employed and compliance of icu staff was assessed. a total of patients were admitted to icu over the set time period and out of them patients were ventilated for more than hours. among them only patients fulfilled the inclusion and exclusion criteria and were enrolled in the present study. excellent compliance was observed in head end elevation, sedation vacation, stress ulcer prophylaxis, and heat moist exchanger filter use, good compliance in oral care and hand hygiene and moderate to poor compliance in subglottic suctioning. the incidence of vap was . % with a vap rate of . / ventilator days. there was a significant correlation between primary diagnosis, hemodialysis, massive blood transfusion and development of vap (p< . )). mean duration of ventilation (p< . ) and mortality (p< . ) were highly significant in vap patients. conclusions: improvement in compliance towards vap bundle and reduction of risk factors can help decrease incidence of vap and related morbidity and mortality. preventive strategies are effective in reducing ventilation-associated pneumonia (vap) in adults [ , ] . in paediatric population there are no data about vap prevention, so we introduced a new bundle (vap-p) based on the available evidence for adults. this was designed as a before-after study. we enrolled all patients admitted to -bed medical-surgical paediatric icu at gemelli hospital in rome, requiring mechanical ventilation for at least hours. patients with pre-existing tracheostomy were excluded. vap-p has been introduced since in order to improve quality of assistance. our bundle consisted in twice a day oral hygiene with chlorhexidine swab, daily check of oral bacterial colonization and aspiration prevention. comparison was made with an historical group including patients admitted before vap-p introduction (since to ). all data about demographics, antimicrobial therapy, icu stay and treatments, were collected. results: patients were included ( after and before vap-p introduction). ( %) events of vap were recorded in vap-p group compared to ( %, p= . ) vap-p group had less vap per days of mechanical ventilation ( / compared to . / p= . ). multivariate analysis yielded an or of . ( %ci . - . ) for vap incidence after bundle introduction. mortality rate was slightly reduced in vap-p group ( . %vs . % p=ns). patients who developed vap required more days on mechanical ventilation and had higher mortality rate ( vs days p< . and %vs % p= . , respectively). our vap-p seems effective in reducing vap incidence in critically ill paediatric population. introduction: ceftolozane/tazobactam (c/t) is a new antibiotic against mdr gramnegative bacteria infections, whose target population are the critically ill patients. even though / g dose safety administered as a hour-infusion has been already assessed, these patients can be under renal replacement therapy (rrt) and suffer changes in their volume of distribution (vd) that may affect antibiotic concentrations. the objective was to determine concentration reached by g c/t ( hour infusion) in septic patients on rrt (cvvhdf) and interdose behavior. we have used rrt machine prismaflex with oxyris filter and m . hplc-uv method was used for simultaneous quantification of c/t. study population consisted of three obese critically ill patients with sepsis, on cvvhdf while receiving g c/t every hours. samples were taken of prefilter, post filter blood and effluent, min before infusion and , and hours after the end of it. we found great interpatient variability with the lowest cconcentration values in the patient with more hemodynamic instability using oxyris filter. even though cmax was less than reported in healthy subjects, we found similar values of auc and t ½ in comparison with healthy population studies. cmax of t was also compromised in comparison with values reported in healthy subjects, but with higher auc and t ½. cvvhdf contributes to c/t clearance. m filter showed the least clearance and higher values of auc and t ½. extraction rate was similar in all patients and filters (figure ) . cmax achieved may be impaired because of the varying vd caused by obesity and rrt, but not affecting the antibiotic characteristics and behaviour. we conclude that because of the variety of clinical conditions, c-concentration is compromised particularly in hemodynamically unstable patients. however, the small sample doesn´t let us extrapolate these results. the extended infusion seems to be adequate to achieve the interdose antibiotic concentration. the use of biomarkers in sepsis is useful for early diagnosis and prognosis. the desired marker should be sensitive, specific, fast and accurate. procalcitonin (pct) measurement is approved by the fda even its efficacy is still under question. the determination of alfatorquetenovirus (ttv) could be a useful marker [ ] . we analyzed samples from patients admitted to icu with clinical suspicion of sepsis. analytical data of c-reactive protein (crp), neutrophils and procalcitonin were collected. the sofa and apache ii scales were calculated and patients stratified according to these values in good and poor prognosis. ttv quantitative determination was carried by using a quantitative crp . we calculated area under the curve (auc) of ttv plasma levels as a function of time. the statistical analysis involved u-mann-whitney and spearman test, using chi for qualitative variables. results showed a not significant (ns) inverse relationship between the ttv auc and the patient proinflammatory level. a tendency (ns) was found between poor prognosis and the pct median values and crp being higher in the poor prognosis.group. a trend showed lower ttv dna count related to worse prognosis. an inverse relationship was found between pct and crp values and the ttv copies /ml plasma, ns correlation in the case of pct. there was a clear trend between the neutrophils´expansion and the regression line slope, obtained between ttv loads in the first two study steps. fig. (abstract p ) . patient pk/pd measurements value> . ), suggesting that the adsorptive mechanism wasn't primarily mediated by plasma protein. ha was saturated after adsorption of a total of . ± . mg of van. the adsorptive kinetics showed an exponential reduction of van mass that reached a plateau after minutes of circulation. in our study, simulating in vivo conditions of hp using ha during sepsis, a rapid and clinically relevant removal of van has been shown. after hours of hp, we suggest to assess van plasma concentration and a loading dose of van should be considered. however, not knowing the potential interactions with other drugs, further in vivo studies are warranted to confirm these findings. assessing the volume of blood taken for blood culture and culture positivitydo we need to take less blood? it is commonly accepted that larger blood culture (bc) volumes (bcv) increase the yield of true positive cultures, and optimally cc of blood should be obtained per set ( bottles). only scarce data exists on the matter of optimal bcv. it is unknown what is the minimal volume that is acceptable for bc. the objective of this study was to determine the association between bcv and the rate of positive bc. blood taken for cultures in bd bactec plus aerobic/f negative bottles was collected from icus and acute care floors at hospitals at the dmc over months. blood volume was estimated automatically from blood background signal data in the bd bactec fx instrument. cultures were analyzed for each bottle. data was summarized for every month as the average volume and number of cultures taken and rate of positive bc for every unit. units were classified according to unit type (icu, medicine, surgery, mixed, emergency department (ed), organ/bmt or "other" which did not fit the previous categories) and analyzed as a group. a total of cultures were taken in units. there is a positive association between bv and positive bc rate for ed and "other" units (irr= . , p= . for the ed, irr= . , p< . for "other" unit). all other units had no association between bv and positive bc rate (figure ). secondary analysis, excluding pediatric units, gave very similar results. when comparing bv between unit types, the ed and "other" unit had significantly lower bv ( . ml in the ed and . ml in "other" unit compared to . ml in the icu, . ml in surgery, . ml in mixed and . ml in bmt). the correlation between bv and positive bc rate is probably limited to units taking very low bv for cultures. units taking volumes above ml show no improvement in positive bc rate when higher volumes are taken. better prospective studies should be done to further establish the minimal bcv needed and spare unnecessary blood loss to hospitalized patients without compromising bc yield. de-escalating antibiotics in sepsis with the use of t mr in a bed greek university icu c vrettou, e douka, i papachatzakis, k sarri, e gavrielatou, e mizi, s zakynthinos st icu department, university of athens, evangelismos general hospital, icu, athens, greece critical care , (suppl ):p in septic patients, the early use of appropriate empiric antibiotic therapy reduces morbidity and mortality. de-escalation refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known. t magnetic resonance (t mr) is a novel method of detecting eskape pathogens. we aim at investigating if using t mr technology can expedite de-escalation of broad spectrum antibiotics. this is a prospective observational study conducted in our -bed university icu. inclusion criteria were critically ill patients age> y.o., with newly diagnosed sepsis and clinical suspicion of eskape bloodstream infection. a sample for t mr and a blood culture (bc) sample were collected simultaneously from the patients enrolled. the t mr bacteria panel test was run according to the manufacturer's guidelines and the bcs were processed according to the hospital standard procedures. we recorded clinical data and administered antibiotics. results: patients were included in the study. mean time to culture positivity was hours while mean time to t mr result was . hours. in patients the results of t mr were in concordance with the bcs. in the remaining cases, the bcs were negative while the t mr detected one or more eskape pathogens. there were no false negative results. de-escalation in at least one drug was applied to patients ( . %). no escalation was applied to patients ( . %) and antibiotic escalation in ( . %). conclusions: t mr provides a quicker detection time that could shorten the time to targeted therapy. in our population this corresponded to early (within - h) antibiotic de-escalation in approximately / of the included patients. antibiotic stewardship in icu. a single experience l forcelledo , e garcía-prieto , l lópez-amor , e salgado , j fernández dominguez , m alaguero , e garcía-carús the increasing antibiotic resistance in microorganisms urged interventions such as the antibiotic stewardship programs in icu focused on reducing the inappropriate use of antibiotics by improving the antibiotic selection, the dosage, administration route and length as well as improving clinical outcomes and reducing antibiotic resistance. retrospective study where antibiotic consumption was analysed and measured in days of therapy (dots) between and in a medical-surgical icu of a university hospital where a multimodal educational program was established. specific training in infectious diseases in critically ill patients, periodic clinical and formative sessions fig. (abstract p ) . correlation of blood culture positivity rate with blood culture volume by unit type were performed for icu staff and specific leaders within the icu staff designated. results: patients were admitted to icu. there was a reduction of , % in dots (figure ), reduction in antimicrobial resistance rates ( , in , , in [days of resistant microorganism/ patientdays]) without an impact in icu global mortality ( , % in , , % in ). the resistant bacteria registered were acinetobacter baumannii, s. aureus mr, blee and carbapenemase-producing enterobacteriaceae, pseudomonas aeruginosa mr and clostridium difficile. the safe in antimicrobial consumption was € ( % reduction). the icu stay decreased from , days ( ) to , ( ) , with no variation in mean apache ii ( , ) . the bigger decrease in antibiotic consumption was in colistin related to the reduction in resistance bacteria, in special acinetobacter baumannii, in linezolid and in piperacilin/tazobactam, even more remarkable in due to shortage of supplies which meant an increase in meropenem. the application of an antibiotic stewardship program in icu succeeded in reducing antibiotic consumption, antibiotic resistance and costs without an impact in clinical outcomes like mortality or icu stay. clinical outcomes of isavuconazole versus voriconazole for the primary treatment of invasive aspergillosis: subset analysis of indian data from secure trial p kundu, s kamat, a mane pfizer limited, medical affairs, mumbai, india critical care , (suppl ):p the secure trial was designed to compare the safety and efficacy of isavuconazole (a) versus voriconazole (v) for primary treatment of invasive mould disease caused by aspergillus and other filamentous fungi. the present analysis is aimed at comparing the indian subset of patients with that of the overall trial population and to ascertain any similarity or difference in the primary efficacy endpoint and safety/tolerability in these two groups. in secure trial, patients in one group received (i) & another patients received (v). the indian subset had patients. we have done a qualitative analysis as the sample size of the indian subset was small. non-inferiority of (i) to (v) in terms of all cause mortality from first dose to day was assessed in overall patients. the treatment difference between (i) and (v) group in the indian subset of patients was analyzed. proportion of patients who had to discontinue treatment due to teaes was analyzed. the all-cause mortality in the overall trial population met noninferiority margin (table ). in the indian subset, it was higher for (i) than (v). there was a lower incidence of ocular, hepatobiliary, skin & subcutaneous tissue disorders in the (i) treated patients (see table ). in indian subset, the above adverse events were less in the (i) group, but statistical inference could not be done due to small sample size. however, similar trend of less number of patients discontinuing therapy due to teaes in the (i) treated patients was seen in the overall patients & the indian subset. the all-cause mortality in the indian subset was higher in the (i) patients. a trend similar to the overall population regarding safety parameters favoring (i) was seen in the indian patients. considering the significantly higher prevalence of ia in india, suitably powered study design is necessary to draw definitive conclusions on the non-inferior efficacy & better safety & tolerability of (i) over (v) in patients of ia. introduction: ventilator-associated pneumonia (vap) is one of the most frequent healthcare-associated infections, correlated with increased mortality,extended hospital stay and prolonged mechanical ventilation. considering the latest outbreak of multiresistant a. baumannii infections in the critically ill patients with vap, there is a growing concern regarding challenges of the antibiotherapy in these patients. although ceftazidim-avibactam is considered to have limited effects on a. baumannii, it is reported to have a synergic activity in combination with other antibiotics. we performed a retrospective, observational study which included icu patients diagnosed with vap(cpis > ). oxa a. baumannii was isolated from the tracheal secretions using a rapid molecular diagnostic platform(unyvero a system). patients were divided in two groups according to the antibiotherapy:group a meropenem + colistin and group b meropenem + colistin + ceftazidim-avibactam.statistical analysis was performed using graphpad applying t-test and kaplan-meier curves, having the in-hospital mortality as primary outcome and days of mechanical ventilation and hospital stay as secondary outcomes. mean age(y.o) in group a was and in group b and in both groups mean charlson comorbidity index was points. survival percent was higher in the group treated with ceftazidim-avibactam ( % vs %, p = . )- (fig. ) . length of stay was significantly decreased in group b ( . days vs days in group a, p = . ). number of days under mechanical ventilation was also decreased in the ceftazidim-avibactam group ( vs ) but the data was not statistically significant. in light of the important thread of multiresistant a. baumannii and the lack of therapeutic measures, the synergistic activity of ceftazidim-avibactam use in combination with other antibiotics may be a promising approach to lower the mortality and hospitalization in critically ill patients diagnosed with vap. impact of patient colonization on admission to intensive care on and days mortality g dabar , c harmouch , e nasser ayoub , y habli , g sleilaty , j infections caused by multi resistant bacteria are a major health problem, especially in icus, and it may be associated with high mortality rates. colonization precedes infection in most instances; therefore it may be a marker of a poor outcome. we tried to determine the impact of colonization on mortality at and days in a population of patients admitted to one medical and one surgical icu in the same institution. medical records review over three years - of all patients admitted to one surgical et one medical icu at hotel dieu de france hospital staying more than h. colonization to resistant bacteria was defined as mrsa, esbl, mdr, and vre. all patient received a nasal and rectal screen on icu admission, in intubated patients tracheal aspirate was considered as colonization in the absence of clinical respiratory tract infection. demographics, apache, sofa, immunosupression, charleston comorbidity index, length of stay, mechanical ventilation, hospitalization and antibiotic use in the previous month were collected. mortality at and days was assessed through medical records or phone call. pearson chi-square was calculated for the association of colonization and mortality at and days, and subsequently odd ratio was estimated. introduction: critically unwell patients have been observed to respond unpredictably to traditional intermittent dosing (id) schedules of vancomycin, likely due to the complex physiological derangements caused by critical illness. continuous infusion (ci) of vancomycin has been suggested to overcome such problems by allowing more regular therapeutic drug monitoring and subsequent effective dose titration [ ] . this study conducted at a tertiary intensive care unit, reports our experience following implementation of a continuous vancomycin infusion protocol. prospective data was collected over two consecuative periods of three months, initially capturing plasma levels for id (target level of - mg/l) followed by reviewing plasma concentration levels in a ci protocol (target level of - mg/l). patients recieving renal replacement therapy were excluded. a total of intermittent vancomycin prescriptions were administered and dosing levels observed. in the three month ci period, patients received ci vancomycin and levels subsequently checked. the ci protocol resulted in increased blood sampling ( samples in ci group vs. samples in id cohort). two non serious incidents were reported in the ci cohort relating to preparation of vancomycin. both groups had a comparable median time to therapeutic range ( hours). however, ci vancomycin group had a greater proportion of first samples outside the desired therapeutic range ( %vs %) (figure ). as the therapy continued, ci vancomycin demonstrated a greater propensity towards consistent therapeutic levels than that observed with id. % of patients on a ci regime achieve the desired target levels compared to % in the id cohort (fig. ) . it was positive for single or multiple microbes in ( . %) and ( . %) samples respectively. single or multiple resistance genes were detected in ( %) and ( %) samples respectively. bfpcr was positive only for bacteria in ( . %), virus in ( . %) and for both in ( . %) cases. influenza a was found in ( . %) cases. the most common organisms in community and hospital acquired pneumonia were streptococcus pneumoniae ( / ) and a. baumannii ( / ) respectively. bacterial cultures were concordant with bfpcr in / ( %) of positive cases. decisions to change antibiotics could be taken earlier based on bfpcr (p< . ) than if were based solely on culturesboth in culture positive ( . ± . vs . ± . hrs) and negative cases ( . ± . vs . + . hrs) where antibiotics would have remained unchanged. based on bfpcr antibiotics were escalated in ( %) patients and teicoplanin ( / ) was most often stopped. bal bfpcr were obtained significantly earlier, identified more organisms and bacterial resistance than culture reports and lead to more frequent and earlier antibiotic changes. severe community-acquired pneumonia (scap) is a frequent cause of hospitalization and mortality. ceftaroline is efficacious for treatment of cap (port risk class iii or iv). most severe patients were excluded from the clinical trials, so the efficacy of ceftaroline in these kind of patients is unknown methods: this is a health record-based retrospective before-after study in a tertiary care hospital. all scap patients admitted in icu between november and february receiving ceftaroline were included. control group included patients with same inclusion criteria but receiving ceftriaxone. propensity scores to adjust for potential baseline differences between groups were performed. levofloxacin or azythromicin were administered in both groups. primary outcome was the change in sofa score over the first h and secondary were days of mechanical ventilation, respiratory failure at h, need of rescue antibiotics, length of stay and mortality results: there were patients in ceftaroline group and in ceftriaxone group. baseline characteristics were similar except from more intubated patients in ceftaroline group (figure ). there were less respiratory failure at h in patients with ceftaroline treatment (- . % vs. - . %; p , ), but no differences in other organ failures, mortality, days of mechanical ventilation or los. there were more need of rescue antibiotics in ceftriaxone group ( . % vs . . %; p , ). we found more streptococcus pneumoniae isolation in ceftaroline group ( ( . %) vs ( . %); p = . ); more empiric use of oseltamir ( ( . %) vs ( . %); p = . ), but no more influenzae infections ( ( . %) vs ( . %); p = . ). s. aureus was detected in patient in ceftaroline group and in in ceftriaxone group. introduction: acute respiratory failure (arf) due to pulmonary infections is a usual cause of intensive care unit (icu) admission. immigration patterns and iatrogenic immune-suppression have made tuberculosis (tb) a common disease in western europe. severe tb requiring icu care is rare. nevertheless, mortality associated with active tb and arf is poor [ ] . adult patients with tb admitted to icu from - were identified retrospectively. diagnosis was based on: positive cultures of sputum, bronchial aspirates or bronchioalveolar lavage fluid. demographic characteristics, reasons for admission, hiv status, anti-tb treatment and mortality were recorded. total of patients with tb were admitted to icu. mean apache ii score was , ± , . sixteen were male. mean age , ± , years. eight ( %) were hiv-positive, ( %) diabetes mellitus type , ( %) chronic liver disease. six ( %) had other causes of immunesuppression. main causes for icu admission were arf due to non- mycobacterium tuberculosis pathogens in %, acute liver failure in %, septic shock due to non-respiratory cause in %. overall, % were on anti-tb treatment at time of admission. tb involved the lung parenchyma in all patients. pleural involvement was present in % and lymph node in %. extrapulmonary sites were present in %: urogenital, gastrointestinal, bone marrow. pathogens identified in over-infections: % gram positive coccus, % gram negative bacilli, % fungal, % mdr-pathogen. one patient hiv-positive suffered arf due to pneumocystis jiroveci. overall, % died during icu stay. besides its latent evolution, mortality of tb patients admitted to icu is extremely high. arf due to over-infection seems to be the main cause for icu admission and mortality. better preventive approach of these patients may improve their outcome. introduction: human african trypanosomiasis (hat) is rarely encountered by critical care clinicians, but is an important differential for fever in the returning tropical traveler. late disease is characterized by seizures, fever and multi-organ failure [ , ] . we present an anonymized case presenting from an endemic area in zambia referred for tertiary critical care management. the patient was too obtunded to give informed consent and his relatives could not be contacted despite extensive efforts. a middle-aged man with no past medical history from rural zambia presented to a local clinical officer post with fever and arthralgia. he was treated twice with anti-malarial medication without resolution of symptoms. two months later he was admitted febrile and obtunded to a local hospital with worsening confusion. he was transferred hours by ambulance to our facility in lusaka, which is the only public tertiary critical care unit in zambia results: gcs on arrival was e m v without localizing neurology. microbiology investigations were negative, including for toxoplasma, cryptococcus, hiv or malaria. the patient suffered a generalized seizure followed by a sustained gcs of and was admitted to the icu for invasive ventilation and seizure control. peripheral blood smears demonstrated trypanosomes consistent with hat secondary to trypanosoma brucei rhodesiense. he was commenced on melarsoprol but rapidly deteriorated, with signs of melarsoprol-induced arsenic encephalopathy and subsequent tonsillar herniation. his death was confirmed by neurological criteria. conclusions: icu management of fulminant hat involves supportive neurocritical care plus melarsoprol, a toxic arsenic compound with common side effects of hepatotoxicity and dysrhythmia. arsenic encephalopathy occurs in % of late hat, with a fatality rate of % [ ] . early diagnosis is associated with a % survival rate in developed world travelers repatriated from endemic areas [ ] . lithium chloride to prevent endothelial damage by serum from septic shock patients (in vitro study) a kuzovlev the aim of the study was to investigate into effectiveness of lithium chloride (licl) as agent that prevents damage to the monolayer of endothelial cells under the action of serum from multiple trauma patients with septic shock. methods: serum from pts with septic shock (sepsis- ) and healthy donors was withdrawn. monolayer of ea.hy endothelial cells were incubated for hrs at °c with healthy person's serum and with septic patient's serum without licl and with it at concentrations of . mmol, . mmol, mmol, mmol. licl was added hour before the change of serum. after incubation cells were washed and fixed with % paraform solution and permeabilized with % triton x- solution. fixed cells were stained with primary antibodies to vecadherin and then incubated with secondary antibodies conjugated with oregon green fluorescent dye as well as with phalloid red and hoechst dye . images were processed by fluorescence microscope and imagej . p and metavue . programs. western blotting was used to detect antibodies to ve-cadherin, claudin and gsk- beta. statistics included mann-whitney test and chi-square test. incubation of a monolayer of endothelial cells with % serum of septic shock patients led to loss of ve-cadherin contacts and decrease of claudine. preincubation with licl . mmol did not prevent dismantling of claudine, actin, ve-cadherins; . mmol licl prevented it (p> . ), but at higher concentrations ( mmol, mmol) almost completely protected endothelial monolayer from destruction of intercellular contacts (p< . ). serum had almost no effect on the phospho-gsk- β level after min, min, min and hr, but caused a significant ( %) decrease in its level after and hrs. licl ( mmol) caused a significant increase in phospho-gsk- β already mins and up to hrs after exposure. licl prevents septic damage to the monolayer of endothelial cells in vitro in a gsk- beta mediated way. introduction: the autonomic nervous system (ans) controls both heart rate and vascular tone, which are known to be impaired during septic shock (ss) . acute inflammation is presumed to increase arterial stiffness of large arteries in experimental studies [ ] . the objectives of this work are to verify if standard ss resuscitation modulate mechanical vascular properties and to verify if alterations in these vascular properties and ans activity are correlated. a protocol of fecal peritonitis septic shock and standard resuscitation (fluids and noradrenaline) was applied on pigs. the arterial blood pressure waveform was recorded in the central aorta and in the femoral and radial arteries. the characteristic arterial time constant tau was computed at the three arterial sites, based on the twoelement windkessel model [ ] . the total arterial compliance (ac) and the total peripheral resistance (tpr) were also estimated. baroreflex sensitivity (brs), low frequency (lf, . - . hz) spectral power of diastolic blood pressure, and indices of heart rate variability (hrv) were computed to assess ans functionality. results: septic shock induced a severe vascular disarray, decoupling the usual pressure wave propagation from central to peripheral sites, as shown by the inversion of pulse pressure (pp) amplification, with a higher pp in the central aorta than in the peripheral arteries during shock. the time constant tau together with ac and tpr were independently decreased. a decrease in brs, lf power, and hrv describe an ans dysfunction. after the administration of fluids and noradrenaline, both vascular and autonomic dysfunction persisted and these were found to be significantly correlated. measures of mechanical vascular function and ans activity could represent an useful end-point to guide further clinical investigations and refine our understanding of ss mechanisms, especially under medical treatment. introduction: lipopolysaccharide (lps), is a component of gram-negative bacteria known for its activation of the host immune system. the phospholipid transfer protein (pltp) has previously been shown to promote the binding of lps to lipoproteins, to limit inflammation and to lower mortality following injections of lps or bacterial infection. the aim of the present study was to investigate the role of pltp and lipoproteins in the detoxification of lps from the peritoneal cavity. injection of lps intra-peritoneally (ip) ( mg/kg) to wild type (wt) and pltp knocked-out mice (pltp-ko) (n = per group). mass concentration and activity of lps were quantitated by lcmsms analysis of -hydroxymyristate and lal bioassay, respectively. lipoprotein fractions in plasma were separated by ultracentrifugation (n= vs n = ). following intra-peritoneal injection, clearance of intra-abdominal lps was faster and plasma neutralization was more efficient in wt than in pltp-ko mice ( figure ) . indeed, lps found in plasma of wt mice was proportionally less active, sustaining a higher capacity for wt mice to neutralize lps (figure b) . quantitative dosage of lps in portal blood, minutes after ip injection, revealed that plasma lps associates rapidly with the lipoprotein fraction (hdl plus ldl), and in higher proportions as compared to pltp-ko mice ( [ - ] % vs [ - ] %, respectively; p < . ). in line with previous studies, these observations now indicate that, lps readily associates with lipoproteins in a neutralizing process pltp mediated. finally, even with a heavy lps load ( mg/kg), the bulk of lps was still found in the lipoprotein fraction ( [ - ] %), suggesting that lipoproteins plus pltp in wt mice have a high capacity to detoxify intraperitoneal lps. in a model of peritonitis, lipoproteins and pltp were found to constitute key playors for peritoneal clearance and neutralization of lps. it emerges as a key pathway for the resolution of the inflammatory response in peritonitis. introduction: autotaxin (atx, enpp ) is a secreted enzyme present in biological fluids that catalyses the production of lysophosphatidic acid (lpa). lpa is a bioactive phospholipid evoking various cellular responses in most cell types. upregulated atx levels have been reported in various chronic inflammatory diseases. given the established role of lpa in the inflammatory response, we investigated a possible role for the atx/lpa axis in lps-induced endotoxemia. methods: lps was injected intraperitoneally ( mg/kg) in mice producing % atx levels (atx df/+ , heterozygous null mutant mice), in mice producing - % reduced atx levels upon inducible inactivation (r creer t /enpp n/n mice) and in mice expressing - % increased atx levels (enpp -tg mice). kaplan-meier survival analysis was performed. atx activity was measured using the toos activity assay. results: atx df/+ mice that produce almost % reduced serum atx levels show increased survival compared to their littermate controls. for the inducible inactivation of atx, enpp n/n targeted mice were crossed with the r cre-er t mice and tamoxifen induction enabled temporal control of floxed gene expression. r creer t /enpp n/n mice were more protected against lps-induced endotoxemia compared to control mice. enpp -tg mice overexpressing autotaxin and showing a -fold increase in plasma levels do not display improved survival rates compared to control group. conclusions: atx participates in systemic inflammation, as reduced atx levels in circulation decrease lethality of mice from caused by lps. the excess amount of circulating atx does not exacerbate the systemic inflammatory response to lps. introduction: pneumonia (pn) is a prevalent and severe infectious lung disease. host genetics plays an essential role in the pathogenesis of infectious diseases including pn [ ] . the aim of the study was to analyze the variability of genes associated with neutrophil activation in pneumonia. to identify differential expressed genes (degs) in communityacquired (cap) and hospital-acquired pneumonia (hap) dataset «genome-wide blood transcriptional profiling in critically ill patients -mars consortium» (gse ) from gene expression omnibus was analyzed (logfc≥ . , fdr-corrected p-value< . ). degs associated with neutrophil activation were selected according to gene ontology go: («neutrophil activation»). with the use of gtex portal and blood eqtl browser, we searched for esnps (expression single nucleotide polymorphisms) in whole blood for neutrophil activation genes differentially expressed in cap/hap. these esnps were further analyzed for their association with pn via the global biobank engine (gbe). a total of degs from gse correspond to go: genes ( up-and down-regulated) of which genes were common to cap and hap. functional enrichment of degs based on disgenet detected top- diseases associated with these genes (fdr-corrected p-value< . ): myeloid leukemia, chronic; sepsis; asthma; lung diseases; allergic asthma. for these genes esnps common to gtex portal and blood eqtl browser were identified. more than half of all variants were located on the second chromosome and influenced the expression of tnfaip and il rap genes. among all esnps we identified variants associated with pn in the gbe (table ) . we identified genes related to neutrophil activation, genetic variability of which was associated with pneumonia. sepsis was induced in wild-type c bl mice (n= ) and cse knockout mice (n= ) by i.p. injection of cfu/mice mdr p. aeruginosa. similar experiments were repeated after cyclophosphamide induced neutropenia. survival was recorded for days. mice were sacrificed for determination of bacterial load and myeloperoxidase (mpo) activity as a surrogate marker of myeloid cell recruitment. cytokines were measured in serum by legendplex inflammatory panel. total leukocytes from mice spleens, with or without pretreatment with the h s donor gyy , were incubated with x cfu/ml mdr p. aeruginosa. bacterial clearance was recorded. we observed a significant decrease in survival of cse -/mice as compared to cse +/+ mice ( % vs. %; p: . ). this survival advantage was eliminated in neutropenic mice ( % for both groups, p: . ). cse -/mice had increased pathogen load in the liver ( . ± . vs . ± . , p: . ) and lung ( . ± . vs . ± . , p: . ). mpo activity was lower in cse -/mice in the liver ( ± vs ± , p: . ) and lung ( ± vs ± , p: . ). cse +/+ mice had increased serum levels of il- ( . ± . vs . ± . of cse -/-, p: . ); mcp- ( . ± . vs . ± . , p: . ) and gm-csf ( . ± . vs . ± . , p: . ). phagocytic activity of leukocytes from cse -/mice was reduced compared to cse +/+ mice. this deficit was eliminated after gyy pretreatment (fig. ) . deficiency of host-derived h s leads to increased susceptibility to mdr p. aeruginosa infection due to an inefficient neutrophil chemotaxis and neutrophil mediated phagocytosis. acknowledgement funded by the itn horizon marie-curie european sepsis academy introduction: neuroinflammation often develops in sepsis along with increasing permeability of the blood-brain barrier (bbb), which leads to septic encephalopathy [ ] . the barrier is formed by tight junction structures between the cerebral endothelial cells [ ] . we investigated the expression of tight junction proteins related to endothelial permeability in brain autopsy specimens in critically ill patients deceased with sepsis, and analyzed the relationship of bbb damage and measures systemic inflammation and systemic organ dysfunction. case series included all adult patients deceased with sepsis in the years - with brain specimens taken at autopsy available. specimens were categorized according to anatomical location (cerebrum, hippocampus, cerebellum). the immunohistochemical stainings were performed for occludin, zo- and claudin. patients were categorized as having bbb damage if there was no expression of occludin in the endothelium of cerebral microvessels. results: % ( / ) developed multiple organ failure before death. . % ( / ) had septic shock. the deceased with bbb damage had higher sofa maximum scores ( vs. , p= . ), and had more often procalcitonin levels above ( % vs. %, p= . ). bbb damage in cerebellum was more common in cases with c reactive protein above mg/l as compared with crp less than ( % vs. %, p= . ). absence of zo- expression in cerebral meningeal samples associated with bbb damage ( % vs. %, p= . ). positive blood cultures (n = ) were associated to absence of zo- expression in cerebellar glial cells ( % vs. %, p= . ). in fatal sepsis, damaged bbb defined as loss of cerebral endothelial expression of occludin ( figure ) is related with severe organ dysfunction and systemic inflammation. loss of zo- in endothelial cells associates with bbb damage, and sepsis contributes to zo- loss in cerebellar glial cells. oxylipins are oxidative breakdown products of cell membrane fatty acids. animal models have demonstrated that various vasoactive oxylipin pathways may be implicated in septic shock pathophysiology but these have been poorly studied in humans. oxylipin profiling was performed on serum samples collected on enrolment to the vanish (vasopressin vs. norepinephrine as initial therapy in septic shock) trial. samples were analysed with liquid chromatography-mass spectrometry. patients were followed up until days. results: samples were collected from of ( . %) patients on inclusion to the trial and ( . %) had died by days. non-survivors were found to have higher levels of a number of oxylipins including: , -dihydroxyeicosatrienoic acid (dhet) (p< . ), , -dhet (p= . ), (s)-hydroxyeicosatetraenoic acid (p= . ), -hydroxyoctadeca-pentaenoic acid (p= . ) but lower levels of the precursor eicosapentaenoic acid (p= . ). when corrected for multiple comparisons with the benjamini-hochberg test, only , -dhet remained significant (p= . ). although there was a difference in median , -dhet levels between survivors and non-survivors, many values were below the level of detection (n= / ( . %)). as such, we also analysed - -dhet as a binary variable (figure ). patients with detectable , -dhet were more likely to die (hr . [ % ci . - . ], p< . ) and have a higher median lactate (p = . ) and total sofa score (p< . ) than those patients where baseline , -dhet was undetectable. our study suggests the oxylipin , -dhet may be associated with septic shock severity and -day mortality. these results are consistent with the known vasodilatory actions of this class of oxylipin. more work is needed to confirm its exact role in septic shock and whether this pathway is amenable to therapeutic intervention. introduction: activation of neutrophils is a mandatory stage and a sensitive marker of systemic inflammatory conditions that can lead to the development of multiorgan failure. the aim of the study was to investigate into the antiinflammatory effects of lithium chloride on human neutrophils in vitro. study was carried out on neutrophils isolated from the blood of healthy donors. % of neutrophils were activated by mkm fmlp, % -by ng/ml lipopolysaccharide (lps); then their activity was evaluated by fluorescent antibodies to cd b and cd b degranulation markers. intact and activated neutrophils were treated with a solution of lithium chloride ( mmol). immunoblotting was used to assess gsk b activity in neutrophils. mann-whitney criterion and p< . were used for statistics. results: lithium chloride mmol decreased the level of expression of cd b on intact neutrophils by % (p= . ), cd b by % (p= . ). fmlp increased cd b expression on neutrophils by . times (p= . ), cd b by . times (p= , ). addition of lithium chloride solution to fmlp activated neutrophils reduced the expression of cd b (p= . ) and cd b (p= . ). lps increased cd b and cd b expression by . times (p= . , p= . , respectively); addition of lithium chloride reduced the expression of cd b (p= , ) and cd b (p= . ) on neutrophils. fmlp led to a dephosphorylation of gsk- b by % (p< . ), lithium chloride increased its phosphorylation by % (p < . ). adding lithium chloride to activated fmlp neutrophils restored the level of gsk- b phosphorylation by % compared to controls (p< . ). lithium chloride modulates the inflammatory activation of neutrophils by bacterial components through the phosphorylation of gsk b in neutrophils. human host immune responses to lipopolysaccharide: a comparison study between in vivo endotoxemia model and ex vivo lipopolysaccharide stimulations using an immune profiling panel dm tawfik introduction: sepsis, a leading cause of mortality among critically-ill patients in the icu, recently recognized by the who as a global health burden. patients that suffer from sepsis exhibit an early hyper-inflammatory immune response which can lead to organ failure and death. in our study, we assessed the immune modulations in the human in vivo endotoxemia model and compared it to ex vivo lipopolysaccharides (lps) stimulation using transcriptomic markers. methods: eight healthy volunteers were challenged with intravenous lps in vivo. in parallel, blood from another volunteers was challenged with lps ex vivo. blood was collected before and after hours of lps challenge and tested with the immune profiling panel (ipp) prototype using the filmarray® system. the use of ipp showed that markers from the innate immunity dominated the response to lps in vivo, mainly markers related to monocytes and neutrophils. comparing the two models, in vivo and ex vivo, revealed that most of the markers were modulated in a similar pattern ( %). some cytokine markers such as tnf, ifn-γ and il- β were under-expressed ex vivo compared to in vivo. t-cell markers were either unchanged or up-modulated ex vivo, compared to a down-modulation in vivo. interestingly, markers related to neutrophils were expressed in opposite directions, which might be due to the presence of cell recruitment and feedback loops in vivo. the majority of ipp markers showed similar patterns of expression post-lps challenge in both models, except for several markers related to neutrophils and t-cells. the ipp tool was able to capture the early immune response in the human in vivo endotoxemia model, which is a translational model mimicking immune host response in septic patients. introduction: serum levels of tyrosine kinase receptor mer and its ligand gas predict mortality in septic patients in the intensive care unit. however, whether their early measurement at emergency department (ed) presentation also predicts mortality and organ failure still needs to be clarified. in this multicentre observational study, septic patients admitted to italian eds were included [ ] . at ed presentation blood samples were taken for routine biochemical analyses and serum mer and gas measurement. urinalyses, blood gas analyses and chest x-ray were routinely performed. mortality at and days, as well as the presence of organ damage such as acute kidney injury (aki), thrombocytopenia, pt-inr derangement and sepsis-induced coagulopathy (sic) were evaluated according to baseline levels of mer and gas . in conclusion, neither mer nor gas are early predictors of mortality in septic patients at ed presentation. however, mer independently predicted the development of sic, thrombocytopenia and pt-inr derangement in this population. glycocalyx shedding correlates with positive fluid balance and respiratory failure in patients with septic shock n takeyama, y kajita, t terajima, h mori, t irahara, m tsuda, h kano aichi medical university, department of emergency and critical care medicine, aichi, japan critical care , (suppl ):p endothelial hyperpermeability would play a major role in septic shock related organ failure. the aim of this study is to clarify the relationship between glycocalyx shedding and respiratory failure, sofa score, plasma angiopoietin (ang)- level and patient survival. methods: plasma samples were collected from septic shock patients from admission to icu discharge and healthy volunteers. plasma syndecan (syn)- and ang- were measured and clinical data was also collected. septic shock patients were classified into groups according to the time-course change of syn- levels. excess syn- (> ng/ml) during to days and remaining high following to days were assigned to group i. excess ang- during to days and decreased following to days were assigned to group ii. moderate increase (< ng/ml) during to days were assigned to group iii. results: plasma syn- levels are positively associated with increased ang- levels (r = . , p= . ), suggesting that ang- is involved in endothelial hyperpermeability. fluid balance and ventilator-free days (vfd) are significantly increased in group i as compared with group iii. sofa score, apache ii and patient outcome does not show any differences between groups i, ii, and iii. the positive correlation between glycocalyx shedding and fluid balance indicates plasma syn- may be a valuable marker for endothelial hyperpermeability. the negative correlation between glycocalyx shedding and vfd indicates plasma syn- may be a valuable marker for respiratory failure. the plasma level of syn- for prognosis and organ failure excluding ards in patients with septic shock requires further investigation. serial procalcitonin measurements in the intensive care unit at hiroshima university hospital k hosokawa, s yamaga, m fujino, k ota, n shime hiroshima university hospital, department of emergency and critical care medicine, hiroshima, japan critical care , (suppl ):p introduction: serum procalcitonin (pct) is a promising biomarker for differentiating bacterial infections from other inflammatory states. moreover, including serial pct measurements in the management of acute respiratory infection reduces the duration of antibiotic therapy without increasing the mortality. however, limited real-world information is available regarding the use of pct in intensive care units (icus). we extracted and analysed data from january to december , from all the orders and results of pct measurements in the icu ( beds) at hiroshima university hospital. a total of , pct measurements from icu patients were included. in patients, pct was tested ≥ times during a single icu stay. serial pct measurements showed a fade-out pattern ( [ %] patients), a second day-peaked decrease pattern ( [ %] patients), and a series of negative patterns ( [ %] patients). compared to patients who demonstrated the fade-out pattern, those who demonstrated the second day-peaked decrease pattern had higher mortality rates ( % vs. %, p < . ). approximately one-third patients in the icu who had decreasing serial pct values demonstrated the second day-peaked decrease pattern. since this group of patients had poorer survival, further studies are needed to clarify the association between a late rise in pct levels and delayed therapeutic intervention. the research was performed on full-term newborns; no clinical signs of bacterial infection were diagnosed. on the , , days the plasmà concentration of il- ß, il- , il- , tnf-α, g-csf, sfas, fgf, no was determined by capture elisa; cd cd , cd cd , cd cd , cd , cd , cd , hla-dr, cd , cd , cd cd , lymphocytes in apoptosis -immunophenotype analysis. by applying the statistical cluster population analysis of the immunological criteria under study we have evaluated the feasibility of sepsis diagnostics at the admission to the intensive therapy unit. the diagnostic rule for sepsis has been formulated by applying the "decision tree" approach to the "r" statistic medium. the cluster analysis confirms the presence of two clusters (presence of absence of sepsis: these two components explain the . % of the point variability). the diagnostic rule for the early diagnostics of sepsis is as follows: disease develops providing during the first hours cd ≥ . %, no≤ . mkmol/l or cd ≤ . %, cd ≤ . %, cd ≥ . % or cd ≤ . %, cd ≤ . %, cd ≤ . % and lymphocytes annexinv-fitc+pi-≥ . %. newborns featured the confirmed sepsis development. the accuracy of this diagnostics amounts to . %; sensitivity to . %; specificity to . %; diagnostic false positive share to . %; diagnostic false positive share to . %; positive result accuracy to . %; negative result accuracy to . %. the aggregate determination of cd , cd , annexinv-fitc+ pi-, cd and the plasma concentration of no enables the pre-clinical diagnostics of sepsis development. efficacy of pancreatic stone protein in diagnosis of infection in adults: a systemic review and metaanalysis of raw patient data j prazak , p egimann , i irincheva , mj llewelyn , d stolz , lg de guadiana-romualdo , r graf , t reding , hj klein , ya que fig. (abstract p ) . impact of h lactate and bio-adm values in patients with elevated lactate level at admission. the green curve in the left km-plot illustrates data from patients with events; the red curve patients with events. the green curve in the right km-plot illustrates data from patients with events; the red curve patients with events. of note, differences in numbers between admission (n= ) and h (n= ) is related to initial mortality introduction: adrenomedullin (am) is a peptide synthesized in vascular endothelial cells and cleared by the lungs. the use of am as an inflammatory biomarker and his predictive value has been studied in critically ill patients, but not yet in veno-venous extracorporeal membrane oxygenation (ecmo). the purpose of this study was to describe the plasmatic levels of am in patients supported with ecmo for acute respiratory failure methods: am (normal values < . nmol/l) was measured at time points: immediately before (t ), -h (t ) and -h after (t ) ecmo initiation and immediately before (t ) and -h (t ) after ecmo removal, in consecutive patients with severe respiratory failure supported with ecmo enrolled in the gatra study (nct ) at fondazione irccs ca' granda -policlinico of milan. data are reported as median ( th - th percentile). statistical analysis was performed using logistic and random effects regression models (to account for repeated measurements within individuals) results: a total of measurements were taken in consecutive patients. am (nmol/l) decreased along the course of ecmo: t = . ( . - . ), t = . ( . - . ), t = . ( . - . ), t = . ( . - . ), t = . ( . - . ) (mean diff.= - . , %: ci - . , - . ). am was lower in patients with viral compared to bacterial ards (mean diff.= - . , %ci - . , - . ) (figure ). am was higher in more severe patients (sofa>= , n= ) compared to less severe patients (sofa< , n= ): . ± . vs . ± . nmol/l, respectively p< . . basal values of am could not predict mortality at days (or= . , %ci: . - . ) after conditioning for sofa score and respiratory failure etiology conclusions: am plasmatic values seem to be higher in more severe patients and in patients with bacterial ards. am decreased along the ecmo course but could not predict mortality in our group of patients fig. (abstract p ) . plasmatic adrenomedullin during ecmo heparin binding protein (hbp) is released from activated neutrophils upon stimulation of b integrins. this pro-inflammatory effect generates the hypothesis that it can be a sepsis biomarker for patients admitted at the emergency department (ed) methods: the prompt study (clinicaltrials.gov nct ) took place at the ed of six greek hospitals. participants were admitted with suspected acute infection and at least one vital sign change. hbp was measured by an enzyme immunosorbent assay in plasma. sepsis was diagnosed by the sepsis- criteria. the primary study endpoint was the sensitivity for the diagnosis of sepsis. outcome prediction was the secondary endpoint. a total of patients were enrolled; had sepsis. the most common infections among patients without and with sepsis were upper respiratory tract infections in . % and . %; community-acquired pneumonia in . % and . %; and acute pyelonephritis in . % and . %. median hbp was . and . ng/ml respectively (p: . ). following analysis of the area under the curve (auc) it was found that the best discriminatory cut-off for sepsis was . ng/ml. the comparative diagnostic performance of hbp versus qsofa score is shown in figure . the odds ratio for sepsis with hbp above . ng/ml was . (p: . ). at the same cut-off point the sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) for the prediction of early death after hours was %, . %, . % and % respectively. hbp is more sensitive but less specific than qsofa for the diagnosis of sepsis in the ed. the rule-out prediction of early death seems the great merit. chronobiological and recurrence quantification analysis of temperature rhythmicity in critically ill patients introduction: rhythmicity and complexity of several circadian biomarkers, such as melatonin, cortisol and temperature have been found to be modified by critical illness. we examined the potential alterations of core body temperature (cbt) fluctuations and complexity in three groups (n= ): patients with septic shock upon icu admission (group a, n= ), patients who developed septic shock at icu hospitalization (group b, n= ) and controls (group c, n= ). the hourly, average cbt was computed for h upon icu admission and discharge in groups a and c, as well as during septic shock onset in group b. cosinor analysis of cbt curves was performed leading to the estimation of mesor (mean value), amplitude (the difference between peak and mean values) and acrophase (phase shift of maximum values in hours). complexity of cbt signals was evaluated with recurrence quantification analysis (rqa). no significant alterations in any circadian feature within groups were found, except for amplitude. controls exhibited increased entry cbt amplitude ( . ± . ) compared to groups a ( . ± . , p < . ) and b ( . ± . , p < . ). higher entry cbt amplitude in groups b and c was related with lower saps ii (r = - . and - . , p < . ) and apache ii scores (r = - . and - . , p < . ) respectively, reduced icu and hospital stay in group b (r = - . and - . , p < . ) and entry sofa score in group c (r = - . , p < . ). recovery cbt time series appeared more periodic in relation with icu entry, for all groups. a more random cbt signals pattern upon results: among . . individuals, . received inpatient treatment for sepsis. % had severe sepsis. % of sepsis and % of severe sepsis patients had an explicitly coded hai. the proportion of hai was higher in patients that received icu-treatment than in patients without icu-treatment ( % in icu/ % in non-icu sepsis, % in icu/ % in non-icu severe sepsis patients). tab. shows the foci of explicitly coded hai. nosocomial pneumonia was the most common hai in all patient groups. clabsi occurred more frequently in icutreated patients; % were affected. cauti and c. diff infections were more common among non-icu-treated sepsis patients. more than one quarter of non-icu-treated sepsis patients had a c. diff infection. hai are common causes of sepsis and pose a significant healthcare burden. the proportion of patients affected and the distribution of foci differ between non-icu-and icu-treated sepsis patients with important implications for sepsis management within hospitals. impact of sepsis protocol triggered by ramathibodi early warning score (rews) in ipd sepsis on clinical outcomes s matupumanon , y sutherasan , d junhasawasdikul , p theerawit sepsis is now early identified and managed during triage in the emergency department. however, there is less focus on the effect of patients' management at the ward level. we aim to evaluate the impact of the implementation of the sepsis protocol on clinical outcomes in in-patients with new-onset sepsis. we conducted a prospective observational cohort study among adult medical patients admitted to the general wards in a university hospital. a -month pre-protocol period (august to august ) was assigned to a control group, and a -month protocol period (september to october ) was allocated to a protocol group. an in-patient sepsis protocol comprised nurse-initiated sepsis protocol by ramathibodi early warning score (rews)≥ plus suspected infection, prompt antibiotic, lactate measurement, and fluid resuscitation was implemented. (table ) . the implementation of in-hospital sepsis protocol was associated with significant improvement in patients' outcomes, namely lactate measurement, starting antibiotic within hr, fluid management, and the shorter length of icu stay. icu routine nursing procedures interfere with cerebral hemodynamics in a prolonged porcine fecal peritonitis model sl liu , dc casoni , w z'graggen , d bervini , d berger , sj jakob routine nursing procedures (np) can interfere with blood pressure and cardiac output and may therefore alter cerebral hemodynamics in critical illness. this may be risk factor of sepsis-associated encephalopathy. methods: sedated and mechanically ventilated pigs were randomized to fecal peritonitis or controls (n= , each). after hours of untreated peritonitis, the animals were resuscitated for hours (resuscitation period). np [assessment of sedation (as), tracheal suctioning (ts), change in body position (cp), lung recruitment maneuver (rm)] were performed at baseline and h, h, h and h after start of rp. systemic and cerebral hemodynamics and o saturations were recorded continuously. shock is the most common cause of death in the postsurgical icu, including septic shock and hypovolemic shock, reaching the - % mortality in septic shock. the inadequate response of the immune system to the infection triggers a potent inflammatory cascade, where the c-reactive protein (crp) is an essential key in the amplification and maintenance of this cascade. the gene encoding to crp is located on the proximal long arm of human chromosome ( q ). the gt polymorphism in the promoter sequence of crp gene (rs ) has been associated with invasive pneumococcal disease. thus, we analyze the relationship between rs polymorphism and the risk of developing septic shock in postsurgical patients. an observational, retrospective and single-center study was conducted on a sample of caucasian patients undergoing major abdominal surgery, of which one part developed septic shock and another part developed systemic inflammatory response syndrome, who were used as control. the rs polymorphism was analyzed by vasoactive medications are commonly used in sepsis treatment but may correlate with peripheral ischemia and the well-publicized complication of limb and digit loss. yet, the association between limb and digit threat and the intensity, duration, and pattern of vasopressor exposure are unknown. we studied adults ( - ) at hospitals in an integrated health system who met criteria for sepsis- . we identified the time to clinically apparent limb or digit threat using clinical adjudication among those with vasopressor-dependent sepsis (i.e. > hour of vasopressors at sepsis onset) who had a surgical evaluation within -days of sepsis onset. we defined daily vasopressor intensity as to vasopressors administered. then, we created a time-dependent model for threat with mortality as a competing risk with a weight function to estimates the varying contribution of vasopressors over time. we determined the subdistribution hazard (sh) ratio of threat for various patterns of vasopressor exposure and intensity, adjusted for age, baseline risk factors, and sequential organ failure assessment (sofa) score at sepsis onset. of , adults with sepsis, , ( %) were vasopressordependent (age, [iqr, - ]; , [ %] males; max sofa score, [sd ] ). of these, , ( %) died and ( . %) had evaluations for limb or digit threat [iqr, - ] days after sepsis onset. the model-based weight function showed the contribution of vasopressors to threat was stable over time ( fig a) . overall, a unit increase in cumulative vasopressor exposure was associated with risk of threat (sh ratio, . [ %ci, . - . ], p<. ). for various patterns of vasopressor exposure, greater intensity associated with increased risk of threat ( fig b) . compared to constant exposure, an increasing and peak pattern associated with the greatest sh (fig c) . cumulative vasopressor exposure was associated with an increased risk-adjusted hazard of limb or digit threat following sepsis. fig. (abstract p ) . relationship between vasopressor exposure and limb or digit threat following vasopressor-dependent sepsis. panel a demonstrates the estimated contribution of daily vasopressor intensity prior to surgical evaluation for limb or digit threat, with mortality as a competing risk. panel b and c explore the relationship between threat and both cumulative vasopressor exposure and the pattern of exposure following sepsis onset. (b) the maximum cumulative vasopressor exposure was associated with the highest risk of limb or digit threat (shr . ) when compared to reference exposure pattern (shr . , reference). (c) increasing (shr . ) and peak (shr . ) patterns of cumulative exposure were associate with an increased sh of limb threat, while a decreasing pattern was associated with a lower risk (shr . ) when compared to constant intensity (shr . , reference). abbreviations: shr: subdistribution hazard ratio proportion of encounters transitioning from phenotype at presentation within hrs, by arrival phenotype assignment and probability of membership. (c) tsne plots for α-type, ß-type, y-type, and ∂-type, with core (dark), marginal (light), and non-members (grey) in plots on the left and core, marginal, non members, and transitioning members (black) on the right fig. (abstract p ). isolated microorganisms critical care references: . wertz et al. critical care explorations : e the process investigators choosing wisely guidelines for the provision of intensive care services, version . ics structured patient handovers references: . care of the critically ill woman in childbirth the proqol manual: the professional quality of life scale:compassion satisfaction, burnout & compassion fatigue/secondary trauma scales references: . shimabukuro-vornhagen a et al. ca the code: professional standards of practice and behaviour for nurses, midwives and nursing associates p introduction: the aim of this study was to compare factors associated with the icu mortality for vap due to multidrug-resistant (mdr) klebsiella spp. in case of monobacterial (mo) vs polibacterial (po) origin. methods: retrospective data analysis of patients treated in icu with mdr klebsiella spp. strains as pathogens of vap during three year period was carried out. results: data of patients were evaluated. mo vs po of mdr klebsiella spp. vap cases was found to be ( . %) vs ( . %), p = . . the icu mortality was / ( . %) in mo, and / ( . %) in po one, p = . . statistical significant differences of survivors vs non-survivors in mo and po vap due to mdr klebsiella spp. were found in medians of neutrophilosis p introduction: we study the population structure and resistome of mdr enterobacterales and pseudomonas aeruginosa isolates, c/t-susceptible or -resistant, recovered from low respiratory, intraabdominal and urinary tract infections of icu patients of portuguese hospitals (step study results: in e. coli, two vim- producers were found (st -b -h -o :h -ctx-m- and st -c-h -o :h ) (c/t-mic= . / - / mg/l). a kpc- -st -cladev-h -o :h ( / mg/l) was also detected. the most frequent esbl-e. coli clone was st cpr klebsiella pneumoniae ( patients), candida spp. ( patients). the comparison subgroup consisted of patients with bacteremia caused by non-escape pathogens. we evaluated the days of mechanical ventilation, duration of antibiotic therapy (amt), icu length of stay (los), hospital los and mortality (table ). results: mortality in patients with bacteremia caused by non-eskape pathogens was . %, candida spp vancomycin mass removal over minutes of hemoperfusion using ha . bars refer to vancomycin mass (mg): blue (experiment ) and red (experiment ) bars using blood while green (experiment ) bar using balanced solution. yellow dashes are mean mass values of the three experiments (with standard deviations) and yellow line represents the reduction curve over time table (abstract p ). results. * p-value versus non-eskape subgroup mechanical ventilation p translational value of the microbial profile in experimental sepsis studies sp tallósy , a rutai , l juhász , mz poles , k burián , d Érces , a szabó , m boros invasive hemodynamic monitoring and blood gas analyses were performed on anesthetized animals between - h of sepsis. the respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions were evaluated with the species-specific sequential organ failure assessment (sssofa) score, the microbial profile was determined with selective media and maldi-tof ms in the initial inoculum and in the abdominal fluid taken h after sepsis induction. results: strong correlation was found between the initial dose of the inoculum (cfu) and the sssofa scores for organ dysfunction (rats: r = . , p= . ; pigs: r= . , p = . ) p introduction: pancreatic stone protein (psp) has shown promise as a biomarker of infection however, its diagnostic potential has not been systematically evaluated. we performed a systematic review and meta-analysis of available data on psp to evaluate its value for detecting infection in adults and determining a plasma or serum threshold value. methods: the pubmed and cochrane library database were searched for studies on psp in adult patients and their raw data were analyzed to estimate the best psp cut-off value that could detect infected patients using the youden's index. the cut-off sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) were computed and compared to those for procalcitonin (pct) and c-reactive protein (crp). finally, we explored the potential value of a model combining all three biomarkers to detect infection. results: from a total of potentially eligible published studies, containing patients were included in quantitative analysis. among them, patients suffered from a clinically confirmed infection. the median appropriate statistical tests were used using spss . cd was expressed as % age of neutrophils expressing positivity. results: sixty patients were analyzed. all parameters were compared between survivors and non survivors. demographics were comparable. most common source of sepsis was lungs and majority were admitted due to medical reason. non-survivors had significantly increased number of days with septic shock. at day median values of all the biomarkers and the sofa score were significantly higher in the nonsurvivor group (p< . ). there was a decreasing trend of all biomarkers and sofa score amongst survivors. on multivariate logistic regression analysis, increased cd and crp levels between baseline and day , increased days with septic shock and increased sofa references: introduction: we characterized the association of c-reactive protein (crp) with extracellular vesicles (evs) in plasma from sepsis patients and assessed a commercial crp adsorbent (pentrasorb, pentracor, hennigsdorf, germany) to deplete free and ev-associated crp. in addition, we characterized the potential pro-inflammatory effects of ev-bound crp on monocytes and endothelial cells monocytes and human umbilical vein endothelial cells (huvecs) were stimulated with isolated evs ( , g, min) monocyte il- secretion was quantified by elisa; the activation of huvecs was assessed by their expression of icam- and e-selectin using confocal microscopy. results: septic plasma (n= ) contained . ± . mg/l crp vs. . ± . mg/ l for healthy controls (n= ). both, total evs and crp + evs were significantly elevated in septic plasma as incubation of septic plasma with pentrasorb resulted in depletion of free crp ( . ± . mg/l before vs. . ± . mg/l after adsorption) as well as in a significant reduction in crp evs from crp-depleted septic plasma induced significantly lower il- levels. huvec icam- or e-selectin expression, however, did not increase upon stimulation with septic evs. conclusions: treatment of septic plasma with pentrasorb efficiently removes free crp and detaches crp from the ev surface, resulting in reduced proinflammatory effects flow cytometry confirmed the association of monocytes with platelets and platelet-derived evs as well as the uptake of evs by monocytes. conclusions: storage of isolated monocytes induces a shift towards cd expressing proinflammatory monocytes, which seems to be mediated by residual platelets and platelet-derived evs. it remains to be clarified whether evs released from activated platelets can also trigger a shift towards proinflammatory, intermediate monocytes in vivo ethical approval was provided by ucl research ethics committee ( / ). paired parametric analyses were performed and data displayed as mean +/- % ci. results: plasma calprotectin concentration began to increase . hours after endotoxin administration, was significantly higher than baseline by hours ( . ng/ml vs. ng/ml, p < . ), peaked at hours (mean ng/ml, figure ) and normalized by hrs. calprotectin peaked earlier than comparator soluble mediators (procalcitonin hrs, crp, hrs) and exhibited % sensitivity; all participants demonstrating a minimum -fold increase from baseline (mean . x). calprotectin displayed greater baseline variability (sd . ng/ml) than either crp or procalcitonin. conclusions: our results indicate the potential of plasma calprotectin as a biomarker for bacterial infection. it increases earlier and peaks more rapidly than standard biomarkers. whilst higher baseline variability was observed p a multicenter randomized controlled study on landiolol for the treatment of sepsis-related tachyarrhythmia: subanalysis of the j-land s study o nishida kagoshima university graduate school of medical and dental sciences, department of emergency and intensive care medicine methods: we analyzed a retrospective cohort of electronic health records from adult sepsis patients at upmc hospitals from to . we defined sepsis- by i.) suspected infection (e.g., administration of antibiotics or body fluid culture) & ii.) organ dysfunction (e.g., or more sofa points) in the first hours of care. data were organized by hour and included vital signs, lab values, and treatments (e.g., total hourly iv fluids (ml) and norepinephrine equivalent dose). for each hour we describe, i.) available data elements, ii.) presence of sepsis- , and iii by hour , most patients had vital signs ( %; n= , ), basic labs ( %; n= , ), fluid cultures ( %, n= , ), while serum lactate was completed in % (n= , ) conclusions: early sepsis care patterns are variable. iv fluids were given during early hours, when uncertainty about sepsis was greatest, while vasopressors were administered after sepsis- elements were present. p effects of abdominal negative pressure treatment on splanchnic hemodynamics and liver and kidney function in a porcine fecal peritonitis model sl liu department of intensive care medicine splanchnic hemodynamics and laboratory parameters were measured at baseline (bl, start of rp), and h, h and h after start of rp. two/three-way rm-anova or mixed-effects analysis, and student t tests were performed. results: npt in controls had no effect. after sepsis induction, mean arterial pressure (map) decreased by ( - ) mmhg, cardiac output (co) by . ( . - . ) l/min, and arterial lactate increased by . ( . - . ) mmol/l. sepsis and resuscitation was associated with increasing hepatic and renal arterial flows (p≤ . , both), and increasing prothrombin time npt in sepsis resulted in numerically less noradrenaline administration ( . ± . ug/ min/kg in sepsis with npt vs. . ± . ug/min/kg without npt, p= . ) and positive fluid balance ( . ± . ml/h/kg with npt vs. . ± . ml/h/kg without, p= . ). conclusions: in our experimental fecal peritonitis model, npt did neither impair splanchnic hemodynamics nor abdominal organ function. whether npt helps to reduce noradrenaline and volume administration in abdominal sepsis should be evaluated in further studies. p association between a c-reactive protein gene polymorphism (rs ) with the risk of develop septic shock in postsurgical patients of major abdominal surgery p martínez-paz valladolid, spain; hospital of medina del campo notably, the three groups received a comparable pro kg dose of acetaminophen. no difference was found between groups in term of toxic effects. patients carrying the cyp a p showed a more pronounced effect on body temperature in respect of wt and ugt a p °c respectively, but it does not reach statistical significance (fig. b). only % of the patients reach a temperature < °c at t and only % < . °c. conclusions: polymorphisms in enzymes involved in the metabolism of acetaminophen are relatively common. cyp a p seems to lead to higher peak plasmatic concentration and a slightly increased efficacy in fever control panel a: variations of acetaminophen plasmatic levels after minutes (t ) and hours (t ) after administration of an iv dose of g of paracetamol in wt patients and patients carrying mutation; panel b: body temperature variations in wt patients and patients carrying mutations clinical research, investigation, and systems modeling of acute illness (crisma) center, department of biostatistics we determined phenotype cohesiveness using probability of assignment at presentation, defining core members as ≥ % and marginal as < % probability. we determined how members transitioned to other phenotypes over hrs using t-distributed stochastic neighbor embedding (tsne) plots and determined the odds ( %ci) of transition. results: we studied , adult sepsis encounters (median age c) the odds of ever transitioning from presenting phenotype increased significantly for marginal members vs publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we thank the department of education of the basque government (piba - ) and the university of the basque country upv/ehu (ppg / , giu / ) for their financial support. a great disaster affects the family-and friend-performance of bcpr by diminishing the willingness of family and friend bystanders to follow the instruction provided by dispatchers. the experimental method ifitem could be an alternative of fibtem in cases when internal coagulation pathways assessment is prioritized (i.e. heparinized patients on extracorporeal supports). patients undergoing limitation of life-sustaining therapy had lower karnofsky scale scores. therefore, this scale may be useful to guide end-of-life decisions in the future, but further studies with larger number of patients are needed. readmission after discharge home from critical care: a qualitative study c robinson , f nicolson , p mactavish , t quasim , jm mcpeake nhs greater glasgow and clyde, nhs greater glasgow and clyde, glasgow, united kingdom; university of glasgow, nhs greater glasgow and clyde, glasgow, united kingdom critical care , (suppl ):p readmissions to acute care occur in a high number of critically ill patients within days of hospital discharge [ ] . biomedical drivers such as frailty and pre-existing co-morbidities have been identified as drivers for readmission. however at present there is limited data on the influence of social problems on readmission. this study, using a grounded theory approach, sought to understand from a patient/caregiver perspective what the drivers for readmission to acute care were. ethical approval was granted from the west of scotland research ethics service ( /ws/ ). a grounded theory approach was used to explore from a patient and caregiver perspective what the drivers for readmission are [ ] . using a clinical database, we identified those patients who had an icu admission ≥ days who were readmitted to acute care within days of hospital discharge. the researcher attended the ward and after discussion with the direct care team conducted a semi-structured interview with patient and/or caregiver. the interview was recorded and transcribed verbatim. the transcripts were analysed to generate initial codes, followed by the development categories and sub-categories. theoretical sampling was undertaken. results: participants were interviewed. ( . %) were patients and ( . %) were caregivers. the themes that have emerged from the data were: pain and polypharmacy; lack of social support and/or isolation; strained relationships with primary care providers and information provision across the patient journey. subsequent theory development is underway to understand how this learning could help reduce readmissions in future. in conclusion, both social and biomedical drivers are likely to contribute to acute care readmission in this group. future interventional work is required in order to identify modifiable factors to reduce this burden for patients and the healthcare service. frailty has shown to have prognostic relevance for patients with critical illness. since a wide range of tools has been described to screen for frailty, we aimed to describe the association of two frailty screening tools, the clinical frailty scale (cfs) score and the modified frailty index (mfi) in critically ill patients. we performed a post-hoc analysis of a multicenter cohort of patients admitted to six canadian intensive care units (icu) between february and july . frailty was identified using the clinical frailty scale (cfs) and the modified frailty index (mfi). concordance of the frailty screening tools was evaluated with partial spearman rank correlation and intraclass correlation (icc). discrimination and predictive ability of the tools for hospital mortality, -year mortality, hospital readmission and adverse events were compared using concordance statistic (c-statistic) and calibration plot adjusting for age, sex, sequential organ failure assessment (sofa) score and icu admission source, respectively. the cohort included patients. prevalence of frailty was . % ( % confidence interval [ci] . %- . %) with the cfs and . % ( % ci . %- . %) with the mfi. concordance between the two tools was low [(icc of . ; % ci . - . ) and partial correlation coefficient of . ( % ci . - . )], even after adjustment. hospital and -year mortality were greater for frail compared to non-frail patients using of both tools. similarly, both tools found frail patients were less likely to be living independently after hospital discharge, and more likely to be rehospitalized when compared to non-frail patients. while the cfs and mfi show low concordance, both showed good discrimination and predictive validity for hospital mortality. both tools identify a subgroup of patients more likely to have worse clinical outcomes. the post-intensive care syndrome (pics) is a myriad of physical, psychiatric and cognitive disorders secondary to critical illness, leading to a decreased quality of life and an important socioeconomic burden. this study aimed to identify if the conformity to a pics prevention bundle was able to reduce the incidence of the syndrome at icu discharge. all patients admitted to the icu from january st to december st were included. the conformity to each of the ten components of the pics prevention bundle was assessed daily, and the patients were evaluated for anxiety, depression, cognitive dysfunction, muscular weakness, mobility impairment and nutritional risk at icu discharge and at a -to- -months follow-up consultation. the patient cohort was divided in terciles according to bundle conformity for the analysis. results: from the enrolled patients, ( %) were evaluated at icu discharge, and ( %) attended to the follow-up consultation. there was no difference in baseline characteristics between the cohorts. there was no correlation between the prevalence of pics at discharge and bundle conformity during icu stay ( % vs. % vs %, p . ), though there was a decrease in nutritional risk and days in mechanical ventilation (table ) . after to months there was a reduction on the prevalence of any kind of pics, mobility impairment, muscular weakness and nutritional risk. the patients that developed pics were older and had a higher simplified acute physiology score iii at icu admission. a higher adhesion to a pics prevention bundle was not able to prevent the occurrence of the syndrome. post intensive care syndrome (pics) is well recognized following general icu care [ ] . intensive care syndrome:promoting independence and return to employment (ins:pire) is a multidisciplinary complex intervention designed to address pics [ ] . with a paucity of evidence on pics after cardiothoracic intensive care, we aim to evaluate pics and the feasibility of the ins:pire intervention in this population. those attending the clinic received weeks of intervention including individual appointments with icm nurse, physician, pharmacist, and physiotherapist. a café area facilitated peer support alongside psychology group sessions. primary outcome was quality of life measured by eq- d- l. further surveys included: pain, mental health, and selfefficacy. questionnaires were taken at baseline, and months. results: over cohorts, patients attended, % male, median age years (iqr - ), median apache score of (iqr - . ), and median icu length of stay was days (iqr - ). a total of ( %) patients completed surveys at one year. scheduled admissions represented % of those attending. mean euroqol eq-vas score was / (sd +/- ) at baseline increasing to / (sd +/- ) by year (table ) . those with problems in at least one domain of eq- d- l fell from % at baseline to % at -year with the breakdown shown in table . severe problems were seen in % falling to % at year. hads demonstrated an anxiety or depression rate of %. brief pain inventory identified patients ( %) with ongoing chronic pain. mean self-efficacy was / (sd +/- ) at baseline and / (sd +/- ) at year. cardiothoracic intensive care patients have ongoing and persistent features of pics with significant effects on health-related quality of life. further, the ins:pire multi-professional complex intervention is feasible within this specialist group. screening approach might be implemented whenever screening of the total icu population is not deemed feasible. influenza is an acute viral illness with a significant financial burden. point of care testing for influenza is available and has demonstrated accuracy [ , ] , the current gap in knowledge is the question around the opportunity cost of influenza testing. if poct is financially a less costly test this could free up scarce resource. the study adopts a cost minimisation approach. the point of care test is the roche cobas® liat® machine which can detect flu a/b and is compared with the west of scotland specialist virology centre's established in house multiplex real time pcr assay.the model was developed using microsoft excel and has arms comparing analysis of the above mentioned tests. the model estimates that the total cost of poct per patient tested is £ . compared with £ . for lab testing ( figure ). this is a saving of £ . per patient when poct is used. the result swings in favour of the lab test when poct specificity falls to . %. if the lab could provide the result of influenza testing within hours the result would swing in favour of lab testing. zanamivir which will potentially be used increasingly in the intensive care setting can more than double the difference between the tests in favour of poct. this research suggests that poct offers potential cost savings in the icu setting. this is the case as long as poct specificity is higher than a threshold of . % and the lab take longer that hours to return the result. the sensitivity analysis should allow for external validity given the usual variations in icu practice. the aim of the present study is to describe the demographic, clinical, microbiological aspects and the outcome of patients with intensive care unit-related (icu-related) bacteremia. moreover, we aimed to study the patient outcome in association with colistin susceptibility. retrospective, single-center study in a -bed icu for months, from / / to / / . icu-related bacteremia was defined as bacteremia in patients with icu stay > hours or icu readmission (first admission ≥ month before). only the first episode of bacteremia was considered. the primary outcome was -day mortality. data regarding clinical, demographic and outcome characteristics were retrieved from the patient files. the hospital's ethics committee approved the present protocol. moreover, the patients with bacteremia due to colistin-resistant pathogens were compared with the patients affected by colistin sensitive microbes. forty episodes of gram-negative icu bacteremia were collected during the aforementioned period in patients ( . % male) with a mean age and apache ii of . ± . years and ± . , respectively. the event had taken place at an average of . days. the responsible isolates were resistant to carbapenems in . % of the episodes. the majority of the events were due to a single isolate ( %). acinetobacter baumannii and klebsiella pneumoniae presented the majority of the implicated microbes ( % and . %, respectively). the crude -day mortality was %. finally, we could not detect any difference in mortality between the colistin sensitive and the colistin-resistant pathogens ( figure ). the present study denotes that, in a setting of extremely drugresistant pathogens with limited treatment options, gram-negative bacteremia in the icu is associated with increased mortality. image : characterization of resistance mechanisms affecting ceftolozane/ tazobactam in enterobacterales and pseudomonas aeruginosa icu isolates using whole genome sequencing (step study) m hernández-garcia , cc chaves , jm melo-cristino , ds silva , ar vieira , mp f. pinto , jd diogo , eg gonçalves , jr romano , rc cantón hospital ramón y cajal-irycis, microbiology department, madrid, spain; introduction: clostridium difficile infection (cdi) is the main cause of hospital acquired diarrhoea [ ] . the aim of this study was to compare characteristics of cdi during yr and . a retrospective observational study was carried out in lithuanian university of health sciences hospital -the largest teaching facility of tertiary care in country. according to department of infection control records, patients (pt) with (w.) diarrhoea and the first positive stool test for c.difficile toxin a/b were included. age, charlson comorbidity index (cci) score, profile of hospital department (medical (md), surgical or icu) where cdi was diagnosed, type of cdi (healthcare-associated (ha), hospital or community-acquired) and rate of risk factors (rf) have been estimated in both and . ibm spss . ; pearson's chi-square, fisher's exact tests were used for statistics. p < . was statistically significant. results: in total pt from , from were enrolled. in n= ( %) pt were ≥ yr old, in -n= ( %), (p= . ). in cci> was estimated in n= ( %) pt in comparison of n= ( %) in , (p= . ). in n= ( %) of cdi cases were ha, in -n= ( %), (p= . ). in n= ( %) of cdi were diagnosed in md in comparison of n= ( %) in , (p= . ). in weeks prior to cdi n= ( %) pt have been admitted to hospitals, n= ( %) have been treated w. antibiotics, n= ( %) -w. ppis, n= ( %) -w. h antagonists, n= ( %) -w. immunosupressants in comparison of n= ( %), n= ( %), n= ( %), n= ( %) and n= ( %) in , respectively, (p> . ). overall rate of cdi cases among in-hospital patients increased tenfold by yr and . in , more elderly patients had cdi and severe comorbidities were less frequent in comparison with . in , more cases of cdi were hospital-acquired and have occured in medical departments. rate of risk factors of cdi remained unchanged.these results indicate a possible relationship between ttv dna count and immunological alteration. the ttv quantitative determination could be useful as a proinflammatory marker in sepsis, with some benefits: low cost, easy determination and good correlation with immune system functionalit. it will be necessary to perform a larger study to check our hypothesis and to establish a ttv level threshold that may allow to anticípate the disease prognosis. introduction: acute kidney injury (aki) is a serious complication in sepsis and associated with high morbidity and mortality. the combination antimicrobial regimens with vancomycin (vcm) and broad-spectrum betalactams (bsbl), such as piperacillin tazobactam and cefepime, have been identified as potentially nephrotoxic combinations, but existing studies have not provided sufficient evidence. the aim of this study was to evaluate detailed association between the combination antimicrobial therapy and the risk of aki in septic patients. this investigation was a post hoc analysis of prospective nationwide cohorts enrolling consecutive adult patients with sepsis in intensive care units in japan. in this study, progression of aki was defined as one or more elevation of renal sub-score in sequential organ failure assessment score from day to day . we regarded anti-pseudomonal penicillins, fourth generation cephalosporines, and carbapenems as bsbl. multivariable logistic regression analysis including a two-way interaction term (vcm x bsbl) was performed to assess the add-on effects of each antimicrobial agent on the progression of aki. the final study cohort comprised patients with sepsis. among them, received vcm without bsbl, received bsbl without vcm, received both vcm and bsbl, and received other type of antimicrobials. the administration of vcm was associated with an increased risk of aki in patients with bsbl [odds ratio (or), . ( . - . ); p= . ]. however, the tendency was not evident in patients without bsbl [or, . ( . - . ); p= . ]. the interaction effect on the progression of aki between vcm and bsbl were statistically significant (p for interaction= . ). the regression model including two-way interaction term suggested that the combination of vcm and bsbl might synergistically increase the risk of aki in patients with sepsis. increasing resistance to carbapenems due to carbapenemase productionone of main actual problems of antibacterial resistance in burn icu. production of several types of carbapenemases (kpc, ndm and oxa- ) is common in k. pneumoniae strains. carbapemenase production is a marker of extreme antibacterial resistance. the aim of our study was to investigate the epidemiology of nosocomial infections caused by producing kpc, ndm and oxa- k. pneumonia strains in burn icu. total of patients with nosocomial infections caused by carbapenem resistance strains of k. pneumoniae were included in the study, from whom had lower respiratory tract infection, had skin and skin structure infection. initial identification of isolates was performed in laboratory by automatic microbiological analyzer. for all of k. pneumoniae isolates presence of bla ndm , bla oxa- and bla kpcgenes were examined by pcr method. baseline characteristics of patients: me (iqr) of age - ( ; ) years, me (iqr) of tbsa - ( ; ) percent, me (iqr) of icu los - ( ; ) days. inhalation injury was diagnosed in ( . %) patients. total of patients died, mortality rate was . %. all patients were diagnosed with nosocomial infection caused by k. pneumoniae. from k. pneumonia strains ( . %) were found to be producing kpc, ( . %)producing ndm and ( . %) -producing oxa . only ( . %) carbapenem resistance k. pneumoniae isolates were not producing carbapenemases. from patients infected by oxa producing k. pneumoniae patients died, mortality rate was %. from patients infected by oxa or ndm producing k. pneumoniae patients died, mortality rate was . %. from patients infected by non-carbapenemase producing k. pneumonia no one died. carbapenemase producing strains are widely spread among carbapenem resistance strains of k. pneumoniae in burn icu. mortality of patients infected by producing oxa or ndm k. pneumoniae strains reaches . %. the rationale for blood purification as adjunctive therapy during sepsis involved the capacity in removing endogenous and exogenous toxins, but currently no recommendations exists [ ] . a critical point may be the potential interaction with antimicrobial therapy, which remains the mainstay of sepsis treatment. the aim of our study was to investigate the vancomycin (van) removal during blood purification using an in vitro model of hemoperfusion (hp) with ha cartridge (jafron, zhuhai city, china), most widely used in china and actually available in europe. this is an experimental study. three independent experiments were performed: we injected mg of van in ml of whole blood from healthy donors (experiment and ) or in ml of balanced solution (experiment ) in order to assess membrane saturation. a closed-circuit (blood flow of ml/min) simulating hp ran using ha . samples were collected from arterial line at , , , , , , , , minutes; van plasma concentrations were measured and removal was evaluated using mass balance analysis. differences in mass removal was assessed using kruskal-wallis test. results: figure shows van mass at each timepoints. we observed no difference between in blood and in balanced solution experiments (p- the aim of this study is to determine if routine bbv testing in the icu contributes to the discovery of undiagnosed bbv infections. icu patients may require renal replacement therapy (rrt). sharing rrt equipment carries a risk of bbv transmission, which mainly relates to hepatitis b (hbv), hepatitis c (hcv) and hiv. since , all glasgow royal infirmary icu patients undergo routine bbv screening, with rrt machines allocated for patients with specific bbv statuses. routine bbv testing is beneficial to both the individual and society. hcv is a pertinent health issue in scotland. the scottish government aims to eliminate hcv by and is researching innovative and costeffective methods to identify undiagnosed infections. this single-centre retrospective observational study examined prospectively collected clinical data from icu admissions. proportions were compared using a two-proportion z-test and a logistic regression model was carried out to determine if deprivation quintile was independently associated with the seroprevalence of bbvs. the bbv seroprevalence in the cohort studied: . % (hbv), . % (hcv), . % (hiv). the seroprevalence of hbv in the cohort studied was similar to that of scotland (p= . ), but the seroprevalence of hcv (p< . ) and hiv (p= . ) were statistically significantly higher than that of scotland. due to the small number of reactive test results for hbv and hiv, the relationship between deprivation and bbv seroprevalence was explored for hcv only. the only independent variable associated with a reactive anti-hcv test result was "current or previous illicit drug use" (adjusted odds ratio of . ; % confidence interval of . - . ; p< . ). this study shows that routine bbv testing in the icu is useful in discovering new bbv infections. this is the first observational study focusing on the value of routine bbv testing in an icu setting to our knowledge. continuous infusion vancomycin protocol is a safe, acceptable and effective alternative to intermittent dosing of vancomycin in critical care. ceftaroline is an efficacious treatment in patients with severe cap, admitted in icu. it relates to earlier resolution of respiratory failure and less rescue antibiotics. we need an adequately pragmatic trial to confirm our findings organ dysfunction in scrub typhus, incidence and risk factor a sarkar , a guha , r dey [ , , , , ] . its preads by bite of larval stageof thromboculid mites or chigger [ ] . clinical features may include fever, headache, myalgia, lymphadenopathy, eschar, skinrash. it may also cause pneumonia, renal failure, shock, meningoencephalitis, multiple organ failure [ , ] . our study aims to discuss the incidence of organ dysfunction in a comprehensive way taking the overall population of patients with identified scrub typhus infection. there is lack of data in eastern india regarding the incidence and risk factors of developing multiorgan dysfunction syndrome (mods) in scrub typhus. in this retrospective study we studied the incidence of various organ involvement and the risk factors associated with the development of mods in scrub typhus. we collected data from december to november in tertiary care hospital at kolkata. we have included all patients who are having fever, scrub typhus igm antibody positive, age more than years. sofa score was used in evaluating patients with mods. exclusion criteria involves patient who are having coinfectional ong with scrub typhus. in a cohort (n= ), patients with multiorgan dysfunction syndrome was seen in patients ( . %), the mean age in group of patients with mods was . +/- . years (mean+/-sd). in group of patients with mods, fever duration in days was of +/- . days (mean+/-sd), interval from treatment to defervescenc in days was . +/- . days (mean +/-sd). among patients with mods, hematologic involvement was seen in patients ( . %), hepatic involvement was seen in patients ( . %), renal involvement was seen in patients ( . %), neurologic involvement was seen in patients ( %), respiratory involvement was seen in patients ( . %), cardiovascular was seen in patients ( . %), icu shifting was necessary in patients ( . %), mechanical intubation was needed in patients ( . %) in multiorgan dysfunction syndrome patients. hospital mortality in patients with mods was patients ( . %). no mortality was seen in patients without mods. other parameters were evaluated among patients with mods. they include eschar in patient ( . %), seizure in patients ( . %), hepatoslenomegaly in patients ( . %), leucopenia in patients ( . %), leucocytosis in patients ( . %), thromnbocytopenia in patients ( . %),decreased hemoglobin in patients ( . %), transaminitis in patients ( . %). the risk factors associated with the development of mods are platelet counts, bilirubin, transaminitis, glasgow coma scale, time interval from treatment to defervescence, hemoglobin, total leucocyte count and fever duration. scrub typhus is an important cause of acute febrile illness in this part of the country and is frequently associated with organ dysfunction. however, the overall mortality is low which is similar to other studies done before [ ] . score at baseline were significant (p< . ) predictors of mortality.highest area under the roc curve was obtained for number of days with septic shock ( . ) followed by increased cd between baseline and day ( . ). though serial pct levels significantly increased amongst non-survivors, it did not predict mortality. serial level of biomarkers in icu patients may predict mortality. larger trials are needed to confirm the results. plasma strem- levels were retrospectively measured at day - , - and - in septic shock patients from the immunosepsis cohort (nct ), included between / and / , using a validated elisa method. the associations between strem- , mhla-dr, -day survival status, and occurrence of icu-acquired nosocomial infection (ni) were assessed. neither strem- nor mhla-dr levels at d / were associated with the occurrence of icu-acquired ni. however, -day mortality was significantly higher in patients with d - strem- value superior to the median ( . % vs . %, p= . ; median= pg/ml). a significant inverse correlation was found between mhla-dr at d - and strem- at d - (sp - . , p< . ) and at d - (sp - . , p< . ). at d - , when stratifying patients based on strem- ( pg/ml) and mhla-dr ( ab/c), patients combining elevated strem- and low mhla-dr presented with significantly higher day mortality ( . % vs . %, p = . , chi-squared test) and ni incidence ( . vs %, p= . ) compared with patients with low strem- / high mhla-dr. this study shows for the first time that trem- pathway activation is associated with septic shock-induced immunosuppression, as shown by an inverse correlation between strem- at baseline and mhla-dr expression at d - . persisting high strem- values and low mhla-dr expression in septic shock patients are significantly associated with higher rate of icu-acquired infection and mortality. introduction: sepsis mortality remains high [ ] . the surviving sepsis campaign (ssc) recommends to guide resuscitation on normalization of lactate levels [ ] , however this is debated [ ] . we have shown that plasma levels of bio-adrenomedullin (bio-adm) were associated with patient outcome during sepsis [ ] . we therefore aimed to evaluate the added value of bio-adm to lactate measurement in the adrenoss cohort. this is a post-hoc analysis of the adrenomedullin and outcome in severe sepsis and septic shock (adrenoss) cohort study. the adre-noss study is a prospective observational study conducted in twenty-four centers and included septic patients [ ] . we studied the relationship between the association of initial evolution of lactate plasma levels and bio-adm level at h and outcome in patients for whom both markers were available at admission and one day later (" h"). bio-adm levels below pg/ml were considered as low, and high if greater than pg/ml [ ] . in patients with high lactate levels (> mmol/l) at admission (n= ), lactate normalization (< mmol/l) at h was associated with better outcome than in patients with persistently high lactate at h ( day mortality . % vs . % respectively, hr . [ . - . ], p< . ) ( figure ). among patients with decreasing lactate, high and low bio-adm levels at h identified patients with different outcomes ( day mortality % vs % for low vs high bio-adm respectively, hr . [ . - . ], p< . ). high and low bio-adm levels at h also differentiated outcome of patients with persistently elevated lactate (hr . [ . - . ], p< . ). in patients with low initial lactate, neither lactate or bio-adm had no added prognostic. our data suggest that measurement of bio-adm in addition to lactate may help physicians to refine risk stratification and therefore to guide resuscitation during sepsis. the effect of fluid replacement in sepsis, severe sepsis and septic shock in first hrs in clot quality and microstructure s pillai , g davies the inflammatory response in sepsis can lead to a spectrum of coagulation system defects [ ] . sepsis and severe sepsis is associated with a hypercoagulable state where the clot microstructure is known to be a tight and highly elastic clot, which is potentially resistant to fibrinolysis ( figure ). conversely, septic shock is associated with a hypocoagulable state where the clot microstructure is loose and structurally weak. the study aim to investigate the effect of fluid resuscitation and replacement in clot microstructure over hours. methods: patients ( sepsis, severe sepsis and septic shock) were included in the study. all these patients received standard fluid replacement therapy with crystalloids. blood samples were collected at hours, hours and hours. clot microstructure, standard markers of coagulation and inflammatory markers were measured. in sepsis group following fluid administration, the d f reduced initially and then remained stable ( . - hours, . - hours, . - hours, normal d f range . ± . ). in severe sepsis group, the d f reduced initially, then increased ( . - hours, . - hours, . - hours) and in septic shock, the df was very low to start with and there were only slight increase with fluid administration ( . - hours, . - hours, . - hours). the hypercoagulable state and clot quality in both sepsis and severe sepsis group improved with fluid resuscitation, however despite an early improvement in clot quality, ongoing fluid resuscitation resulted in markedly reduced functional clot with very low clot strength and functionality. this study demonstrates that d f as a marker of clot quality and function may have potential in fluid and component replacement in critical illness and injury. this study analyses the prognostic ability of white blood cell count (wbc), neutrophil:lymphocyte ratio (nlr) and c-reactive protein (crp). hypo-and hyperimmune responses have been associated with increased mortality from septic shock [ ] . patients with septic shock (sepsis . ) admitted to queen elizabeth hospital birmingham, between december and july were included. the primary outcome was -day mortality. data was tested for normality and presented as median (iqr) and analysed using a mann whitney u test. categorical data was presented as % and analysed using a chi-squared test. a p value of < . was used to determine significance. a multivariate binary logistic regression analysis was conducted using age, apache ii, charlson comorbidity index, performance status, and initial lactate as covariates. a hosmer lemeshow test of > . indicated good fit. results: patients were admitted with septic shock. the majority ( %) were male, with a median age of ( - ) and a -day mortality of %. on day , wbc was lower in patients who died compared to patients who survived ( [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] patients who died of septic shock had a lower wbc, nlr and crp response early on compared to survivors. this may represent early immunoparesis that allows infection to propagate unchecked. however, this was not independently associated with mortality when confounding factors were accounted for. a specific metabolite of mitochondriaitaconic acid is formed upon proinflammatory activation. the attempts of various researches to find the itaconic acid in peripherical blood of patients with sepsis were unsuccessful [ ] . some phenylcarboxylic acids (phcas) are known to be microbial metabolites and sepsis biomarkers; they also affect the mitochondrial functions [ ] . concentrations of phcas (phenyllactic, p-hydroxyphenylacetic, phydroxyphenyllactic acids) and mitochondrial metabolites (succinic, itaconic acids) in serum samples from patients on the st day of diagnosis of sepsis and serum samples from patients with late stages of sepsis (sepsis- ) were measured by gas chromatographymass spectrometry; control group - donors. results: itaconic acid was found in low concentrations ( . - . μm) only at early stage of sepsis. the multiple increase in levels of phcas and mitochondrial metabolites were detected in patients with late stage of sepsis in comparison with early stage and donors, p< . . increased succinic acid (up to - μm) concentration is the result of succinate dehydrogenase inhibition by microbial metabolism intermediates (phcas), which was confirmed by in vitro experiments in isolated mitochondria (fig. ) . itaconic acid may be a promising marker in early stage of sepsis, which needs to be proved. prediction of severe events in clinical sepsis is challenging. for such prediction we aimed to compare the novel biomarker calprotectin in plasma, with routine biomarkers. in a prospective study, blood samples were collected from consecutive patients who triggered the sepsis alert in the emergency department in our hospital. c-reactive protein (crp), procalcitonin, neutrophils, and lymphocytes were analysed according to routine practice. p-calprotectin was analysed using a specific particle enhanced turbidimetric assay (gentian diagnostics as). the composite endpoint, which was termed severe event, was defined as death or admission to the intensive care unit (icu)/high dependency unit (hdu) within hours from arrival. the study included patients with written informed consent, of whom were considered to have infection (defined as obtained blood culture and subsequent antibiotic therapy for at least days or until discharge or death), and had no infection. seventy-four patients ( %) with infection developed a severe event. mean pcalprotectin was . mg/l (standard deviation (sd) . ) among patients with infection and . mg/l (sd . ) among patients without infection (p= . ). in patients with infection mean p-calprotectin was . mg/l (sd . ) among those with and . mg/l (sd . ) among those without a severe event (p= . ). analysis of area under the receiver-operating characteristic (roc) curve for prediction of severe events showed superiority for p-calprotectin compared with procalcitonin and neutrophil-lymphocyte-ratio, both regarding all sepsis alert cases and regarding the patients with infection (p< . for all comparisons), fig . in addition, there was a trend toward superior performance compared to crp (p= . and . ). in sepsis alert patients, p-calprotectin was elevated in those who subsequently developed severe events. p-calprotectin was superior to traditional biomarkers for prediction of severe events. introduction: rapid diagnosis of acute infections and sepsis is critical in emergency departments (eds). current tests have slow turnaround times, low sensitivities, and/or signals from contaminant or commensal organisms. empirical antimicrobial treatment may result in severe adverse events and contributes to antimicrobial resistance. diagnostics to distinguish bacterial from viral infections and noninfectious etiologies support clinicians in efforts toward antimicrobial stewardship. in a prospective, non-interventional study in the eds of sites in greece (prompt study nct ), we evaluated hostdx sepsis, a host response test for suspected acute infections and suspected sepsis. hostdx sepsis measures human mrna targets and employs advanced machine learning to differentiate patients with bacterial and viral infections, and noninfectious etiologies. adult patients presenting with suspected acute infection and at least one vital sign change were enrolled. whole blood rna was quantified using nano-string ncounter. predicted probabilities of bacterial and viral infection were calculated (bvn- algorithm). patients were adjudicated in a retrospective chart review by independent infectious disease specialists blinded to hostdx sepsis results. among patients adjudicated as bacterial ( ), viral ( ), noninfected ( ), or indeterminate ( ) the area under the receiver operating characteristics (auroc) of hostdx sepsis for predicting bacterial vs. viral/non-infected patients was . , and auroc for viral vs. bacterial/non-infected patients was . (fig. ) . our results indicate that hostdx sepsis distinguishes bacterial from viral infections and other etiologies with high accuracy. hostdx sepsis is currently developed as a rapid point-of-care device with a turnaround-time of less than minutes. hostdx sepsis may therefore assist ed doctors in making appropriate treatment decisions earlier, towards the ultimate goal of antimicrobial stewardship. we studied the diagnostic value of a leukocyte deformability assay that rapidly quantifies the immune activation signatures of sepsis in an undifferentiated population of adults presenting to the ed. ed clinicians must balance the benefits of early intervention against the risks of indiscriminate use of resource-intensive interventions. there are no currently available rapid diagnostics with acceptable performance to achieve this balance. we prospectively enrolled adult patients within hours of presentation with signs of suspicion of infection in two eds in the usa. edta-anticoagulated blood was drawn and analyzed using deformability cytometry [ ] . procalcitonin (pct) levels were also measured. patients were retrospectively adjudicated for sepsis- by physician committee using the entire medical record. diagnostic performance characteristics and receiver operating curves were used to examine the diagnostic performance of the assay as well as pct. of the patients enrolled, . % were adjudicated as septic. the leukocyte deformability assay demonstrated % sensitivity, % specificity, and % negative predictive value for a single cutoff. the auc was . ( figure ). pct with a cutoff of . ng/ml had % sensitivity, % specificity, and % negative predictive value. the auc for pct (as continuous variable) was . . the leukocyte deformability assay of immune activation signatures demonstrated superior diagnostic performance for sepsis when compared to pct. the assay's diagnostic performance and rapid turnaround time of minutes may positively impact patient outcomes while minimizing indiscriminate use of valuable resources in the ed. it is already known in literature that high levels of midregional proadrenomedullin (mrproadm) are related with organ disfunction in infections despite of source and pathogens [ ] . similarly, microcirculatory impairment has been reported in sepsis. we examine the correlation between microcirculatory disfunction and mrproadm as a sign of early organ failure. we included consecutive adult patients with suspected infection, sepsis or septic shock admitted to our intensive care unit (icu) as first hospital admission with an expected icu stay of > hours. mrproadm was measured daily during the first five consecutive days and sublingual microcirculation was assessed with incident dark field (idf) technology at t , t , and t . we collected information on saps ii, apache scores, and sofa score for each timepoint. results: ten patients had septic shock, sepsis and infection. three patients died during icu stay. a mrproadm clearance of % or more between t and t was found associated with the improvement of mfi (mann-whitney u test, median increase . % versus . %, p= . ) (figure ) . a mrproadm > . nmol/l at the icu admission was associated with a worse sofa score at all the timepoint. moreover, mrproadm levels at admission was found significantly related with icu mortality (auc . [ . - ]; p= . ). mrproadm shown no relation with absolute value of mfi. the study shows a good correlation between the clearance of the biomarker and the improvement in mfi. moreover, our results support previous findings on the prognostic value of mrproadm in terms of sofa and icu-mortality. clinical performance of a rapid sepsis test on a near-patient molecular testing platform r brandon , j kirk , t yager , s cermelli , r davis , d sampson , p sillekens , i keuleers , t vanhoey immunexpress, seattle, united states; immunexpress, immunexpress, seattle, united states; biocartis nv, biocartis, mechelen, belgium critical care , (suppl ):p the purpose of this study was to clinically validate a new, rapid version of the septicyte™ assay on a near-patient testing platform (biocartis idylla™). septicyte™ lab is the first-in-class sepsis diagnostic to gain fda-clearance but has a complex workflow and a turnaround time (tat) of~ hours. the assay in idylla™ cartridge format is called septicyte™ rapid. septicyte™ lab was translated to the biocartis idylla™ near-patient testing platform and analytically validated. for this study, . ml of peripheral blood paxgene tm solution from previously collected patient samples was pipetted directly into the cartridge and inserted into the idylla™ reader. patients were part of an independent cohort (n= ) from intensive care units located in the usa and europe. septicyte™ rapid results were reported as a septiscore™ between and with higher scores representing higher probability of sepsis. assay performance determined included technician hands-on-time (hot), assay tat, failure rates, and area under roc curve based on comparison to retrospective physician diagnosis. average hot was minutes, and average tat was minutes. clinical samples could be processed immediately with septicyte™ rapid and did not require hour pre-incubation of paxgene blood, greatly improving tat. correlation of septiscore™ values between lab and rapid, based upon a subset of samples run on both platforms, was very high (r > . ). estimated roc auc performance for discriminating sepsis from non-infectious systemic inflammation (nisi/sirs) was similar to that previously reported for septicyte™ lab. this is the first demonstration of a validated, fully-integrated, rapid, reproducible, near-patient, immune-response sepsis diagnostic, providing actionable results~ hr, to differentiate sepsis from non-infectious systemic inflammation / sirs. accuracy of septicyte™ for diagnosis of sepsis across a broad range of patients r brandon , k navalkar , d sampson , r davis , t yager immunexpress, seattle, united states; immunexpress, immunexpress, seattle, united states critical care , (suppl ):p the purpose of the study was to demonstrate sepsis diagnostic performance of the biomarkers of septicyte™ in subjects other than critically ill adults, and in hospital locations other than icu. septicyte™ lab was the first immune-response sepsis diagnostic assay to gain fda-clearance (k ) and, as part of gaining this clearance, clinical validation was performed on adult patients admitted to intensive care (icu) only [ ] . we therefore performed an in silico analysis across a broad range of patients using the septicyte™ host immune response biomarkers and algorithm. peripheral blood gene expression data, including public and private datasets, were chosen based on quality, annotation, and clinical context for the intended use of septicyte™. multiple comparisons were performed within datasets to better understand the diagnostic performance in certain cohorts including healthy subjects. diagnostic performance was determined using area under curve (auc). results: table shows some characteristics of the selected datasets and patients, including number of datasets (n= ) and comparisons (n= ), number of cases (n= ) and controls (n= ) used in comparisons, patient category and hospital location. septicyte™ aucs for the three groups of adults, adult / pediatric and pediatric / neonates were . , . , and . respectively, which is similar to that previously reported ( . - . ) [ ] . these results suggest that the septicyte™ signature has diagnostic utility beyond adults suspected of sepsis and admitted to icu. this signature has now been translated to the near-patient testing platform biocartis idylla™ (as septicyte™ rapid) which promises rapid (~ hour) diagnosis of sepsis in a broad patient population following further validation. introduction: especially extracorporeal cardio pulmonary bypass (cpb) is known to induce severe inflammation. postoperative inflammation is associated with a sepsis like syndrome including endothelial barrier disruption, volume depletion and hypotension. sphingosine- -phosphate (s p) is a signaling lipid regulating permeability and vascular tone. in septic humans decreased serum-s p levels could be identified as marker for sepsis severity. we addressed three main issues: ( ) are serum-s p levels affected by cardiac surgery? ( ) are potential alterations of serum-s p levels related to changes of acute-phase proteins, s p sources or carrier? ( ) is the invasiveness of the surgery a factor that may influence serum-s p levels? methods: elective major cardiac surgery patients were prospectively enrolled in this study. serum samples were drawn pre-, post-procedure and on day and day after surgery. we analyzed s pand its potential sources: red blood cells (rbc) and platelets. we further quantified levels of other inflammatory markers and documented other clinical parameters. median serum-s p levels in all patients before the procedure were . (iqr . - . ) nmol/ml. serum-s p levels decrease after surgery, whereas all other inflammatory markers increase. serum-s p levels dropped by % in the on-pump and % in the off-pump group. changes of serum-s p levels are associated with s p sources and carriers: albumin, hdl and vwf:ag activity. patients with a full recovery of their serum-s p levels after surgery compared to their individual baseline presented with a lower sofa score (p> . ) and shorter icu stay (p< . ). serum-s p levels are disrupted by open heart surgery and levels might be negatively affected by endothelial injury or loss of s p sources. low serum-s p levels may contribute to prolonged icu stay and worse clinical status. future studies may investigate the beneficial effects of s p administration during cardiac surgery. the aim of study is to measure and correlate the expression of ncd , mhla-dr, pct (procalcitonin) and qcrp (quantitative creactive protein) to predict development of sepsis and its outcome. in this tertiary centre based longitudinal cohort study, a total patients were enrolled in whom sepsis was suspected on the basis of clinical diagnosis and supported by lab investigations. they were divided into two groups sepsis/case and non-sepsis/control. disease severity in icu was assessed by sequential organ failure score (sofa). blood samples for routine lab investigations and biomarkers were taken at the time of admission in icu before administration of first dose of antibiotics at time d /d . assessment of biomarkers was done simultaneously with tlc at d /d , d and during follow up of patients till their final outcome. there was no significant (p> . ) mean change in pct, qcrp, sofa, ncd , mhla-dr from day to day , however, mean change was higher among cases than controls.on comparison of mhla-dr between the groups across time periods, mhla-dr was significantly (p= . ) lower among septic patients than controls at both day and day . all biomarker correctly predicted cases among different percentage of patients with different sensitivity and specificity. there was no significant (p> . ) association of mortality with the study biomarkers except for pct. in our study, diagnostic value of pct in differentiating sepsis from non-sepsis was similar to ncd among all biomarkers studied. no advantage of ncd or mhla-dr was found over pct in diagnosis and correlation with disease progression and mortality. introduction: aqp is a water channel protein contributing to astrocyte and immune cells migration, blood-brain barrier maintenance and cell survival [ ] [ ] . aqp genetic variants represent biomarkers associating with outcome after traumatic brain injury and intracerebral hemorrhage [ ] [ ] . linking aqp genetic polymorphism to the course of sepsis has not been studied. methods: study cohort included icu patients diagnosed according to sepsis- consensus. aqp rs polymorphism was studied by analyzing pcr products in a % agarose gel using an aqp specific polynucleotide tetraprimer set. data were analyzed by log rank test (medcalc . . ), and odds ratios/hazard ratios were computed. statistical significance was determined by fisher test (ft) or mann-whitney test. results: of sepsis patients had the minor mutation a for snp rs located within the regulatory ' region of the aqp gene. septic shock occurred more frequently in homozygotic carriers of aqp c allele vs. patients with aa or ca genotype: or= . ( %ci: . - . ), p= . (ft). lethality in septic shock patients, n= , significantly increased compared to sepsis patients with no shock, n= ( % vs. %, p= . , ft). maximum sofa values were significantly lower in patients with minor allele a compared to cc carriers of ( . vs. . , respectively, p= . ). in post-surgery group of patients, carriers of ac or aa genotypes had significantly increased survival compared to patients with cc genotypes: chi-square= . ; hr= . ( %ci: . - . ) for lethality; p= . (figure ) . association of minor allele a of aqp snp rs with survival in sepsis patients seems secondary to linking the snp to decreased development of multiorgan failure and septic shock that contribute to mortality. validation of presepsin as a biomarker of sepsis in comparison to procalcitonin, il- and il- v chantziara , f kaminari , c sklavou , s fortis , p kogionou , s perez , a efthymiou saint savvas hospital, icu, athens, greece; saint savvas hospital, cancer immunology and immunotherapy center, athens, greece critical care , (suppl ):p sepsis is an everyday challenge for the intensivist and biomarkers are useful tools for identification and treatment of this syndrome. we sought to validate presepsin as a biomarker of sepsis in comparison to pct(procalcitonin) and interleukins (il- ,il- ). we enrolled patients, men and women average age ( . - ) years old, apache ii ( . - . ), saps ii ( . - . ), sofa ( . - ). patients were septic on admission (according to surviving sepsis campaign: international guidelines for management of sepsis and septic shock: ), had a septic episode during their hospitalization in the icu while patients never endured sepsis. we measured presepsin, procalcitonin, il- , il- during sepsis and on remission. results: all septic patients had increased values of presepsin, pct, il- and il- during sepsis with a cutoff value for presepsin pg/ml, while the values of these biomarkers were significantly decreased during remission or in comparison to non-septic patients(presepsin p = . , pct p≤ . , il- p≤ . , il- p= . . all patients who were not septic survived while among septic patients died ( % mortality). presepsin correlated significantly with pct, il- and il- (p< . ). presepsin is a valid biomarker of sepsis and correlates significantly with all the other values of pct, il- and il- . clinical sepsis phenotypes are proposed at hospital presentation. these phenotypes, biomarker profiles, and outcomes are not yet reproduced in prospective data. even less is known about the biologic mechanism the drives these distinct groups. thus, we sought to validate clinical phenotypes and to determine markers of innate immunity, coagulation, tolerance and tissue damage in a prospective cohort. we prospectively studied patients with sepsis- criteria within hours of presentation at hospitals in pennsylvania ( - ) using automated electronic alerts. using clinical variables, we predicted phenotypes (α, β, γ, δ) for each patient using euclidean distance anchored to published seneca phenotype centroids. discarded blood was analyzed in a subset (n= ) for markers of innate immunity (e.g. il- , il- ), coagulation (e.g antithrombin iii, eselectin), tolerance (e.g. ho- , igfbp ), and tissue damage (e.g. serum lactate, bicarbonate) results: among patients, α-type was present in ( %), β-type in ( %), γ-type in ( %) and δ-type in ( %, figure a ). on average, β-type was older and more comorbid (mean , sd yrs; mean elixhauser . , sd . ) with renal dysfunction (median creatinine . [iqr . - . ] mg/dl, p< . all). the δ-type had more acidosis (mean hco - . , sd . meq/l), higher serum lactate (median . [iqr . - . ] mmol/l, p < . both) and inpatient mortality ( %, figure b) . the γand δ-type had greater markers of innate immunity and abnormal coagulation (e.g il- , icam p< . both), while markers of increased tissue damage (lactate) and poor tolerance (ho- ) were present in δ-type, compared to α-type (figure c) . the distribution and characteristics of clinical sepsis phenotypes were reproduced in a prospective validation cohort. similar to the seneca study, distinct biomarker profiles of tissue damage, innate immunity and poor tolerance were present for the δ-type. the effect that neoadjuvant chemotherapy and hyperthermic intraperitoneal chemotherapy (hipec) may have in the postoperative kinetics of biomarkers remains unknow. some studies demonstrate that neoadjuvant chemotherapy and hipec do not invalidate the use of inflammatory markers in postoperative patient monitoring, but none have compared biomarkers kinetics between patients who underwent hipec or only cytoreduction surgery. our main purpose was to identify a difference pattern in c-reactive protein (crp). we conducted a single-center observational study from january to november , including all patients who underwent cytoreductive surgery with or without hipec. crp was measured daily until seven post-operative day. we compared patients with and without hipec. a total of patients were included, were female. mean age was yrs ( - ). no clinical and demographical differences were observed between groups. no documented infection was found. after surgery crp increased markedly in both groups. crp time-course from the day of surgery onwards was significantly different in hipec patients ( . ± . mg/dl vs . ± . mg/dl; p= . ). multiple comparisons between hipec and non hipec patients were performed and crp concentration was significantly different on the th and th pod (figure ). no differences were found in other biomarkers (leucocytes and platelets) neither in body temperature. after a major elective surgical insult crp levels markedly increase independently of hipec. serum crp time-course showed a higher pattern in hipec patients despite no infection detected. decreased thrombin generation potential is associated with increased thrombin generation markers in sepsis associated coagulopathy d hoppensteadt , f siddiqui , e bontekoe , r laddu , r matthew , e brailovsky , j fareed. introduction: sepsis associated coagulopathy (sac) is commonly seen in patients which leads to dysfunctional hemostasis in which uncontrolled protease generation results in the consumption of clotting factors. the purpose of this study is to determine the thrombin generation potential of baseline blood samples obtained from sac patients and demonstrate their relevance to thrombin generation markers. baseline citrated blood samples were prospectively collected from patients with sac at the university of utah clinic. citrated normal controls (n= ) were obtained from george king biomedical (overland park, ks). thrombin generation studies were carried out using a flourogenic substrate method. tat and f . were measured using elisa methods (seimens, indianapolis, in) . functional antithrombin levels were measured using a chromogenic substrate method. the peak thrombin levels and auc levels were lower in the sac patients in comparison to higher levels observed in the normal plasma ( table ). the sac group showed much longer lag time in comparison to the normal group. wide variations in the results were observed in these parameters in the sac group. the f . and tat levels in the sac group were much higher in comparison to the normal. the functional antithrombin levels were decreased in the sac group. these results validate that thrombin generation markers such as f . and tat are elevated in patients with sac. however, thrombin generation parameters are significantly decreased in this group in comparison to normal. this may be due to the consumption of prothrombin due to the activation of the coagulation system. thus, persistent thrombin generation with simultaneous consumption of clotting factors such as prothrombin contributes to the consumption coagulopathy observed in sepsis patients. introduction: procalcitonin (pct) is used in the icu as an inflammatory marker to monitor bacterial infections and guide antibiotic therapy. whether pct can predict bacteremia and therefore could prevent expenses attached to bloodcultures is unknown . we investigated whether pct can predict the outcome of blood cultures in the icu and reduce expences. a single centre observational cohort study was performed in a dutch community teaching hospital . adult patients who were staying in the icu and were suspected of bacteremia were included. simultaneously with drawing of blood cultures, samples for pct measurement were obtained. expenses for pct measurement and bloodcultures were calculated. in the study period of one year, a total of patients were included. three patients were excluded because of incomplete data. out of the included patients, ten patients had positive blood cultures. there was a significant difference in pct levels between patients who had positive bloodcultures versus patients with negative bloodcultures ( . ng/ml vs . ng/ml) ( figure ). the negative predictive value for negative blood cultures is % when pct is below ng/ml, there was no difference in crp levels between the two groups ( mg/l vs mg/l, p= . ).a set of negative blood cultures in our centre costs euros. positive blood cultures however costs significantly more depending on the micro-organisms found. pct only costs . euros per measurement. so when blood cultures are omitted when the pct level is below ng/ml, a cost reduction of % can be achieved. a pct value below ng/ml is a good predictor of a negative blood cultures in icu patients suspected of bacteremia. pct guided bloodculture management in these patients could lead to a significant cost reduction introduction: level of cfdna in plasma is a promising prognostic candidate biomarker in critical illness [ ] . oxidized cfdna (ocfdna) have not been studied as a biomarker although its functional role in cellular stress have attracted attention of researches [ ] . the goal of our study was to assess the early prognostic value of plasma cfdna/ocfdna for sepsis in a nicu setting. the cohort included nicu patients diagnosed with stroke, intracerebral hemorrhage (ich), anoxia, encephalopathy. cfdna was isolated from day plasma and stained with picogreen. oxidized dna was determined using dna immunoblotting with anti- -oxo-desoxiguanosine antibodies. genotyping of allelic variants of the tlr rs gene was performed using a pcr and designed allele-specific tetraprimers followed by electrophoretic separation of the products statistics was performed by the fisher test and mann-whitney test. results: sepsis was diagnosed by sepsis- criteria in patients ( . %). average nisu staying was , ± , days. circulating dna plasma levels on day predicted the future sepsis development (figure ): or for cfdna was . ( %ci: . - . ), p< . ; or for ocfdna was . ( %ci: . - . ), p= . . power of both performed tests with alpha= . : . . log rank test demonstrated better predictive value of cfdna vs. ocfdna (figure) . concentrations of cfdna, but not ocfdna, on day significantly positively correlated with maximum sofa values during hospitalization, day and pre-outcome leukocyte count and neutrophil-to-lymphocyte ratios in a limited cohort of nisu patients with tlr rs cc genotype and not in other patients with genotype tlr ct+tt. increased level of plasma cfdna better then ocfdna predicts sepsis development in nisu. further studies are warranted to clarify the fig. (abstract p ) . pct values in patients with positive blood cultures and patients with negative blood cultures possible utility of tlr rs polymorphism determining for sepsis risk stratification early on nisu admittance. admission was related with higher severity of illness and extension of icu stay for all groups. reduced cbt fluctuations upon icu admission was found to more severely ill patients with worse clinical outcomes, while the more periodic cbt patterns were correlated with high cbt rhythmicity and better outcome. the impact of sex on sepsis incidence and mortality have been elucidated in previous studies, and sex is increasingly recognized as one key factor in sepsis [ ] . some studies indicate that women have better immunologic responses to infections [ ] . later investigations assume this advantage is linked to immune modulating genes located on the x-chromosome [ ] . the purpose of this study is to reveal sex differences in incidence of and mortality of sepsis in a large population-based cohort. methods: adult participants in the hunt study ( - ) were followed from inclusion through end of . incident bloodstream infections (bsi) from all local and regional hospitals in nord-trøndelag county were identified through linkage with the mid-norway sepsis register, which includes prospectively registered information on bsi used as a specific indicator of sepsis. we estimated age-adjusted cumulative incidence of first-time bsi and compared the risk of a first-time bsi and bsi mortality in men and women using age-adjusted cox proportional hazard regression. during a median follow-up of . years individuals experienced at least one episode of bsi, and died within days after a bsi. cumulative incidence and cumulative mortality curves are shown in fig. a introduction:the proportion of hospital-acquired infections (hai) among sepsis patients is unknown in germany. systematic differences in hai foci between sepsis patients with and without icu treatment are insufficiently described. retrospective cohort study based on nationwide health claims data of the german statutory health insurance aok. incident inpatient sepsis cases were identified in / among insured persons > y without preceding sepsis in months prior to index hospitalization. sepsis was defined according to explicit sepsis icd- -codes (incl. severe sepsis/septic shock). hai were defined based on specific icd- -codes for surgical site infection, catheter- introduction: elevated renin is associated with an increased risk of death in patients with vasodilatory shock (vs). recent data show that patients with vs and elevated renin levels have improved survival when treated with angiotensin ii (ang ii) + standard care (sc) vs placebo + sc. patients with acute respiratory distress syndrome (ards) can develop angiotensin-converting enzyme (ace) defects that can lead to elevated renin levels and insufficient endogenous ang ii production. we hypothesized that patients with severe ards and elevated renin shock would have improved survival when treated with ang ii + sc vs placebo + sc. in the randomized, placebo-controlled, double-blind athos- study, patients with severe vs receiving > . μg/kg/min of norepinephrine or the equivalent were randomized to intravenous ang ii (n= ) or placebo (n= ). in a post hoc analysis, we assessed the subset of patients with elevated renin (defined as a renin level greater than the median value of the overall athos- population) and ards (defined by a pao /fio ratio < ) at the time of randomization. survival to days was compared between the ang ii group (n= ) and the placebo group (n= ). in patients with elevated renin and ards, baseline age, acute physiology and chronic health evaluation ii score, and blood pressure were similar in the ang ii and placebo groups. the median serum renin level was . pg/ml (iqr: . - . ) compared to the normal range for serum renin: - pg/ml. a significantly higher proportion of patients receiving ang ii survived to day compared to those in the placebo group ( % vs %; p= . ). elevated renin identified patients with vs and ards who were most likely to gain a survival benefit from ang ii. elevated renin is likely caused by an ace defect and may describe an important subset of patients with a biotype that responds well to ang ii therapy. introduction: elevated renin levels have been shown to be associated with an increased risk of death and more severe acute kidney injury (aki) in patients with vasodilatory shock (vs). recent data show that patients with vs and elevated renin levels have improved survival when treated with angiotensin ii (ang ii) + standard care (sc) vs placebo (pbo) + sc. we hypothesized that vs patients with severe aki and elevated renin levels would have improved survival and enhanced renal recovery with ang ii treatment. in the randomized, pbo-controlled, double-blind athos- study, patients with severe vs received > . μg/kg/min of norepinephrine or the equivalent and were randomized to intravenous ang ii + sc (n= ) or pbo + sc (n= ). in a post hoc analysis, we assessed the subset of patients with elevated renin (defined as a renin level greater than the median value of the overall athos- population) and severe aki (defined as those with aki requiring renal replacement therapy [rrt] at baseline). survival and renal recovery were assessed in patients treated with ang ii + sc (n= ) and pbo + sc (n= ). in patients with elevated renin and severe aki, baseline age, acute physiology and chronic health evaluation ii score, and blood pressure were similar between ang ii + sc vs pbo + sc. the median baseline serum renin level in the whole group was . pg/ml (iqr: . - . ; normal range for serum renin: - pg/ml). a significantly higher proportion of patients receiving ang ii + sc vs pbo + sc survived to day ( % vs %, respectively; p= . ). ang ii recipients also had a higher rate of discontinuation from rrt by day ( % vs %; p= . ). in this study, elevated-renin shock patients with aki treated with ang ii + sc gained a survival benefit and earlier discontinuation from rrt compared to those receiving pbo + sc. elevated renin is likely caused by an angiotensin-converting enzyme defect and may identify those patients with a biotype that responds well to ang ii therapy. most clinical trials conclude the ineffective use of anticoagulation for sepsis-induced coagulopathy [ ] . however, post hoc analyses of randomized control trials report positive results [ ] , suggesting anticoagulation is effective in specific populations exhibiting coagulopathy. further, anticoagulants should be administered in the early phase [ ] ; however, methods for precisely predicting the progression of sepsis-induced coagulopathy are not established. this study aimed to create and evaluate a prediction model of coagulopathy progression using machine-learning techniques. we performed a subgroup analysis of data from a retrospective cohort study involving adult septic patients in japanese institutions from january to december and used the japanese association for acute medicine disseminated intravascular coagulation (dic) score as a dic severity index test. the predictive ability of Δdic ([dic score on day ] -[dic score on day ]) was evaluated using various statistical methods. using variables available at the outset, we compared the predictive ability of random forest (rf) and support vector machine (svm) with that of multiple linear regression analysis. a total of adults with sepsis were included in the analysis. the root mean square error in Δdic score for the multiple linear regression analysis model was . compared with values of . and . for rf and svm, respectively. thus, the rf method predicted the progression of sepsis-induced coagulopathy more accurately than multiple linear regression analysis. conclusions: rf, a machine-learning technique, was superior to multiple linear regression analysis in predicting the progression of sepsis-induced coagulopathy. this prediction model might enable us to use anticoagulation in an early phase. this study examined the efficacy and safety of landiolol, an ultrashort-acting β -blocker, for treating sepsis-related tachyarrhythmia, according to patient background characteristics. the j-land s study (japiccti- ) was conducted in patients with sepsis, diagnosed according to the sepsis- criteria, and tachyarrhythmia (atrial fibrillation, atrial flutter, or sinus tachyarrhythmia). the patients had a mean heart rate of ≥ beats/min and required catecholamine administration to maintain a mean blood pressure of ≥ mmhg. the efficacy endpoint was the percentage of patients whose heart rate could be controlled within - beats/min at h of registration. the safety endpoint was the incidence of adverse events within h of registration. subgroup analyses of efficacy and safety were performed after stratifying the patients according to various patient background characteristics. a total of patients were randomized, to landiolol and to the control group. the efficacy endpoint, percentage of patients with a heart rate of - beats/min at h of registration, was significantly higher in the landiolol group ( . % vs . %; mantel-haenszel test: p = . ). the incidence of adverse events was . % and . % in the landiolol and control groups, respectively, and there was no difference between the two groups. most adverse events were related to sepsis or septic shock. the subgroup analyses showed that no patient background characteristic clearly affected the efficacy and safety of landiolol. landiolol is a well tolerated and effective therapeutic agent for controlling heart rate in patients with sepsis-related tachyarrhythmias; its safety and efficacy were not affected by the patient background characteristics investigated. tissue oxygenation monitoring in sepsis r marinova, at temelkov umhat alexandrovska, anesthesiology and intensive care, sofia, bulgaria critical care , (suppl ):p near-infrared spectroscopy (nirs) was proposed as a concept in the end of th century. this method offers noninvasive monitoring of oxy-and deoxyhemoglobin in tissues.nirs could be measured on the thenar or forehead within few santimeters of the skin. it was first applied as a monitoring in cardiovascular surgery. patients with sepsis have changes in the microcirculation which are important target for therapy. invasive monitoring of oxygen delivery and consumption has been used in patients with sepsis but as every invasive technique such a monitoring hides risks. nirs offers a noninvasive method for tissue oxygenation monitoring (sto ) and could be useful in patients with sepsis and septic shock. the aim of the study is to compare noninvasive tissue oxygenation monitoring with hemodinamic monitoring and lactate values in patients with sepsis methods:the study includes critically ill patients in icu of umhat alexandrovska, sofia. of the patients fullfil the criteria for septic state. the other patients do not have sepsis. in both group of patients are measured tissue oxygenation with invios monitor, mean arterial pressure, oxygen saturation in mixed venous blood and lactate values during h after icu admission. patients with sepsis are reported with significantly lower values of tissue oxygenation, compared to patients without sepsis. the values of tissue oxygenation correlate well with the mixed venous blood oxygenation, mean arterial pressure and lactate values but not significantly with apache scores. conclusions: nirs when used for tissue oxygenation monitoring correlates well with the hemodinamic monitoring and lacate values in patients with sepsis and could be used as an noninvasive monitoring for guiding teurapeutic strategies. tissue oxygenation monitoring has no linear correlation with the severity of illness in patients with sepsis and could not be reccomended as a guidance in the early ressuscitating stage of sepsis. further investiganions in these field are needed.the sequenom´s massarray platform and a recessive inheritance model was selected (cc vs tt/ct). the possible association between the cc recessive form of the rs polymorphism and the septic shock risk was analyzed, demonstrating a statistically significant relationship (p= . ) between both conditions. among patients who developed septic shock, . % presented a recessive inheritance pattern while . % showed the ct/tt genotype. on the other hand, those patients with the recessive form of the rs polymorphism were selected and a statistical analysis was performed comparing those patients who developed septic shock from those who did not develop it, obtaining a statistically significant relationship (p= . ) between the presence of the recessive form of polymorphism and the likelihood of developing septic shock. the recessive form of rs polymorphism is a risk factor for septic shock in post-operative patients of major abdominal surgery. introduction: sepsis remains one of the major causes of morbidity with mortality rates as high as % worldwide, representing significant clinical challenge to confront highly intangible therapeutic needs. rnabased structures are emerging as versatile tools encompassing a variety of functions capable to bypass the current protein-and cellbased therapies. rna aptamers act as disease-associated protein antagonists. here, the effects of an aptamer, apta- , were evaluated in animal models that mimic systemic inflammation in humans. high dose of lps endotoxin was used to induce systemic inflammation in mice and in non-human primate animal models. apta- was administered intravenously in two doses post lps infection. animals were monitored and blood samples collected up to hours after apta- administration. healthy-and lps-only treated animals served as control groups. complex analyses of clinical parameters, hematology, serum biochemistry, inflammation and tissue damage markers were performed. results: apta- increased survival of endotoxin challenged animals up to % in a dose-dependent manner and exerted profound effects on wellbeing and recovery of healthy eating habits. administration of apta- led to delayed coagulation and enhanced fibrinolysis; maintained the complement cascade activated while preventing it from further amplification. expression of pro-inflammatory cytokines was reduced while anti-inflammatory increased. endogenous pro-inflammatory molecules (damps), secreted from injured cells, were preserved at healthy level in animals treated with apta- . systemic inflammation and sepsis lead to severe dysregulation of several arms/axis of innate immune response. our studies showed that apta- affects various components of this system and restores the organism's control over its dysregulated immune response. thus, apta- might be a promising potential therapeutic candidate to treat life-threatening conditions such sepsis. several preclinical studies demonstrated beneficial effects for methane (ch ) administration in various inflammatory conditions. our aim was to investigate the consequences of post-treatment with inhaled ch in a clinically relevant intra-abdominal sepsis model. anesthetized minipigs were subjected to fecal peritonitis ( . g/kg, - x cfu i.p.; n= ) or sham-operation (sterile saline i.p; n= ). invasive hemodynamic monitoring with blood gas analyses was started between - hours, organ dysfunction parameters (pao /fio ratio; mean arterial pressure; lactate, bilirubin, creatinine; urine output and platelet counts) were determined according to a modified porcinespecific sequential organ failure assessment (ps-sofa) score system, the perfusion rate (pr) of sublingual microcirculation was measured by incident dark field illumination imaging. the animals were divided into non-treated septic or septic shock groups (n= - ) and ch treated septic or septic shock (n= - ) subgroups, ch inhalation started from the th hr ( . % ch in normoxic air; ml/min). despite the standardized induction, heterogeneous severity of organ damage was evolved. in septic and septic shock groups the median values of ps-sofa score reached ( . - . ) and ( . - ), respectively. septic shock was characterized by significant elevations of creatinine and bilirubin levels, while the platelet count decreased (from to * /l). inhalation of ch increased the sublingual pr by % in the septic group, the creatinine and bilirubin levels were decreased by % and %, respectively. ch post-treatment significantly decreased the ps-sofa score (to ; . - . ) and resulted in lower values in septic shock group (to ; . - . ). methane post-treatment effectively influences sepsis-related end organ dysfunction. up to a severity threshold it may be a promising additional organ protective tool. evaluation of sepsis awareness among various groups in turkey: a survey study s erel, o ermis, Ö nadastepe, l karabıyık gazi university school of medicine, anesthesiology and intensive care, ankara, turkey critical care , (suppl ):p introduction: sepsis is a common life-threatening condition in critically ill patients [ ] . public awareness is important for early recognition of sepsis and improvement of outcomes [ ] . we aimed to evaluate sepsis awareness among different groups of people. methods: prospective paper-based surveys were issued between st july and st august to patients, the relatives of the patiens, hospital staff and general public who gave consent to participate in the study. the questionnaire included ten questions about demographic informations, occupational informations of hospital stuff and sepsis awareness. a total of participated in the survey. of these participants, ( . %) were patients, ( . %) were relatives of patients, ( . %) were physicians, ( . %) were medical students, ( . %) were nurses, ( . %) were other hospital stuff and (% . ) were other people. of these participants, ( . %) had heard of the word "sepsis". ( . %) responded correctly regarding the definition of sepsis. ( . %) of the participants heard the word "sepsis" during their education, but only ( %) heard it through the media. in the groups of high school graduates, university graduates and postgraduates, the rate of hearing the word sepsis and correctly identifying sepsis is significantly higher than the primary school graduates or illiterate groups. (p< . ). physicians, nurses and medical students were heard of the word "sepsis" significantly more than other groups (p< . ). physicians and medical students responded more accurately to the definition of sepsis than other groups (p< . ). public awareness of sepsis is limited compared to healthcare workers. increasing public knowledge of sepsis through education and through media may contribute to raising public awareness and improving outcomes. the association between clinical phenotype cohesiveness and sepsis transitions after presentation jn kennedy , eb brant , km demerle , ch chang , s wang , dc angus , cw seymour key: cord- -m lkrehi authors: nan title: proceedings of réanimation , the french intensive care society international congress date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: m lkrehi nan introduction: veno-venous extracorporeal co removal (ecco r) is a promising new therapeutic option in the critical care setting. we conducted a prospective observational study of the use of ecco r in selected voluntary centers during years aiming to assess the prevalence of the ecco r use mainly among copd and ards patients. patients and methods: two medical devices: hemolung (alung technologies, pittsburgh, usa) and ila activve (xenios novalung, heilbronn, germany) were selected after literature and medico-economic evaluations. a specific medical and nurses training was provided in table characteristics of patients with known or de novo svv (small-vessel vasculitis) admitted to the intensive care unit for acute respiratory failure (arf) all arf (n = ) immune arf (n = ) non immune arf (n = ) p age , introduction: ineffective triggering is frequent during pressure support ventilation (psv). its occurrence is favored by dynamic hyperinflation that may arise when increasing the pressure support level (psl). decreasing the psl however fails to suppress ineffective triggering in a subgroup of patients that are therefore exposed to refractory ineffective triggering. proportional assist ventilation with load-adjustable gain factors (pav +) decreases the incidence of ineffective triggering in unselected patients but its effect on refractory asynchrony during psv is unknown. the main aim of our study was to assess the effect . the median gain during pav + was % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the asynchrony index was significantly lower with pav + than psv ( % [ ] [ ] [ ] [ ] [ ] [ ] [ ] vs. % respectively, p = . ). moreover, the asynchrony index decreased in every patient with pav + (fig. ) . noticeably, the tidal volume was already protective in psv and decreased even more during pav + ( . ml kg [ . - . ] vs. . ml [ . - . ] respectively, p = . ); and the neural respiratory rate was high in both modes ( cycles min in psv vs. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in pav + , p = . ). total esophageal pressure-time product (ptpes) did not significantly differ between the two modes but the ptpes proportion that was wasted in ineffective efforts decreased with pav + ( % [ ] [ ] vs. % , p = . ). conclusion: our preliminary data suggest that: ( ) pav + reduces the incidence of refractory ineffective triggering; ( ) patients exposed to refractory ineffective triggering during psv seem characterized by rapid shallow breathing despite high ventilatory support, questioning the tolerance of both ventilatory modes. results with further inclusions will be presented. introduction: the use of alternatives to carbapenems to treat patients with extended-spectrum beta lactamase-producing gram negative bacilli (esbl-gnb) infections remains controversial. their use in patients with severe infections in the icu has been poorly studied. the aim of this study was to compare the outcome of icu patients having received carbapenems to those having received a carbapenem-sparing agent (csa). the charts of patients with esbl-gnb infection hospitalized in our icu between and were retrospectively reviewed. patients treated with betalactam betalactam inhibitor (bl bli), cefepime or quinolones were considered has having received an alternative to carbapenems (csa). patients having received such a csa were compared to those having received a carbapenems. primary outcome was treatment failure at day , defined as esbl-gnb infection recurrence (relapse with same pathogen) or death, whichever first occurred. results: patients with esbl-gnb infection were included. source of infection was the lung for most of them. characteristics of patients are displayed on table . their median saps ii and sofa scores were and [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , respectively, and ( %) were on septic shock. patients received a carbapenem empirically, among whom were switched to a csa agent when antibiogram was available (csa-definite group), whereas carbapenems were pursued in the others (carbapenem-only group), mainly because pathogens were resistant to others antibiotics. among the patients having received a non-carbapenem agent as empirical treatment, pathogen was susceptible to this agent in and they pursued the same treatment (csa-only group), whereas were switched to a carbapenem (pathogens resistant to empirical treatment, carbapenem-definite group). treatment failure were not different among these groups (table ) . globally, patients received a csa as their definite treatment (csadefinite and csa-only groups), whereas received a carbapenems (carbapenems-only and carbapenems-definite groups). whereas duration of antimicrobial treatment was similar ( [ - ] days vs. [ - ] days, respectively, p = ns), treatment failure rate was not higher in the former, as compared to those having received a carbapenems ( vs. %, respectively, p = . ). conclusion: treatment of patients with esbl-gnb severe infection in the icu with a csa seems to be safe when the pathogen is susceptible to this csa. however, mic should be first determined before de-escalating to a csa. larger studies are needed. percentages of samplings which attained the pk pd targets for various crcl with potential suboptimal beta-lactam concentration in critically-ill patients with aki treated either with an early or a delayed rrt strategy. patients and methods: ancillary study in a subset of patients with severe aki (kdigo ), receiving a beta-lactam antibiotic, in a trial comparing two rrt initiation strategies. in this trial, patients from intensive care units were randomly assigned to either an early (immediate rrt) or a delayed (late or no rrt) rrt initiation strategy. beta-lactam residual concentrations were sampled at and h after inclusion. the appropriate concentration was defined as a trough of at least times the minimal inhibitory concentration (clinical breakpoint of eucast). the primary outcome was an adequate plasma concentration of the beta-lactam during the first days. results: among the patients included in the centers participating to this ancillary study, a beta-lactam trough concentration was evaluated in subjects, in the early and in the delayed groups. ninety patients ( . %) had an adequate beta-lactam dosage. rrt initiation strategy had no impact on beta-lactam concentration (p = . ). among the septic shock patients ( % of the sampled patients), ( %) had a correct antibiotic concentration. in contrast, only of the patients without definite sepsis ( . %) had a correct dosage. factors associated with an adequate beta-lactam trough concentration in univariate analysis were admission for a septic shock (p = . ), a higher plasma creatinine level (p = . ), a higher mean arterial pressure (p = . ) and a lower serum bicarbonate level (p = . ) at randomization. a higher sofa score was associated with an adequate beta-lactam concentration near to statistical significance (p = . ). multivariate analysis will be presented. in the context of severe aki, beta-lactam concentration reached a sufficient level in % of septic shock patients. interestingly, rrt initiation strategy was not associated with beta-lactam trough concentration. early rrt did not affect trough concentration of betalactam. we may hypothesize that physicians were highly vigilant and adapted antibiotic administration adequately in these patients. introduction: amikacin infusion requires to target a peak serum concentration (c max ) - times the minimal inhibitory concentration, corresponding to a c max at - mg l − for the least susceptible bacteria. recent study reported that % of critically ill patients do not attain this target with a mg kg dose ( ) . membrane sequestration, alteration of the volume of distribution and lack of data in this population make drugs pharmacokinetics (pk) on ecmo challenging. our study aimed to assess the prevalence of insufficient amikacin c max in critically ill patients on ecmo and to identify relative risk factors. patients and methods: prospective, observational, monocentric study of adult patients on venoarterial (va) or venovenous (vv) ecmo receiving a loading dose of amikacin for suspected gramnegative infections. intravenous amikacin was administered with a loading dose of mg kg of total body weight and c max was measured min after the end of the infusion. independent predicators of c max < mg l − after the first amikacin infusion were identified by mixed model multivariate analysis. results: from january to february , patients (median saps (interquartile range) ( - ); age ( - ) years) under va-ecmo ( %) or vv-ecmo ( %) were included. at inclusion, the sofa score was ( - ) and ( %) patients were on renal replacement therapy. overall icu mortality was %. c max was < mg l − in ( %) of the patients. independent risk factors of amikacin under-dosing were body mass index (bmi) < kg m − (odds ratio (or) . , % confidence interval %ci . - . , p = . ) and a positive h fluid balance (or per ml increment: . , %ci . - . , p = . ) (fig. ). our results were comparable to those observed in patients treated with amikacin without ecmo ( ) . conclusion: this large prospective study suggests that the prevalence and associated risk factors of amikacin under-dosing are similar in critically-ill patients with or without ecmo. the use of a mg kg dose in low bmi patients and in those with a positive -h fluid balance on ecmo is strongly encouraged to obtain adequate therapeutic targets and prevent therapeutic failure. results: fifty patients were included ( with delirium, controls), at day for controls and day for patients with confusion. delirium patients were more severely ill sofa [ ; ] versus [ ; ] (p = . ); with higher rass [ ; ] versus [ ; ] (p = . ). they presented with % bl overdosing versus % in controls (p = . ); with % of bl in therapeutic index: % in controls (p = . ). obesity and renal failure were not associated with bl overdosing but there was a trend with hypoalbuminemia (p = . ). discussion: trend in association of bl overdosing with delirium corresponds to previous studies, and would need a larger scale study to be confirmed. severity differences in groups would need changes in inclusion criteria to obtain homogeneous groups. a possible association of bl underdosing with poor evolution of infection and organ failures would need more precise evaluation. hypoalbuminemia could have an impact on bl overdosing. conclusion: delirium was not associated with bl overdosing but with therapeutic index. a high variability of bl concentrations warrants therapeutic drug monitoring. a larger scale study should include changes in design. feasibility and safety of low-flow extracorporeal co removal with a renal replacement platform to enhance lung protective ventilation in patients with mild to moderate ards schmidt matthieu , jaber samir , constantin introduction: extracorporeal carbon dioxide removal (ecco r) might allow ultraprotective mechanical ventilation with lower tidal volume (vt) (< ml kg ideal body weight), plateau pressure (pplat) (< cm h o), driving pressure, and respiratory rate (rr) to reduce ventilator induced lung injury (vili). the aim of this study was to assess the feasibility and safety of ecco r with a renal replacement platform (rrt) to permit ultra-protective ventilation in patients with mild to moderate acute respiratory distress syndrome (ards). patients and methods: twenty patients with mild (n = ) or moderate ards were included. vt was gradually reduced from to , . and ml kg − and peep adjusted to reach > pplat > cm h o. standalone ecco r (no hemofilter associated on the rrt platform) was initiated when arterial paco increased by more than %. ventilation parameters (vt, rr, peep), respiratory compliance, driving pressure, arterial blood gases, and ecco r system operational characteristics (blood flow, sweep gas flow, and co removal rate) were collected during a minimum of h of ultra-protective ventilation. complications, mortality at day , need for adjuvant therapies and data on weaning from both mechanical ventilation and ecco r were also collected. results: while vt was reduced from to ml kg − and pplat kept below cm h o, peep was significantly increased from . ± . at baseline to . ± . cm h o at vt = ml kg − . as a result, the driving pressure was significantly reduced to . ± . cm h o at vt = ml kg − (p < . ) (fig. ) . no significant differences in rr, pao fio ratio, respiratory system compliance were observed after vt reduction. mean extracorporeal blood, sweep gas flow and co removal were ± ml min − , ± . l min − and ml min − , respectively. mean treatment duration was ± h. main side effects related to ecco r were membrane clotting which occurred in patients after ± h. conclusion: a low-flow ecco r device driven by a rrt platform efficiently removed co while allowing ultra-protective mechanical ventilation settings in patients with mild to moderate ards (clinicaltrials. gov identifier: nct ). morimont philippe , habran simon , desaive thomas , janssen nathalie , amand theophile , blaffart francine , dauby pierre , kolh philippe , defraigne jean-olivier , lambermont bernard introduction: protective lung ventilation (plv) is recommended in patients with acute respiratory distress syndrome (ards) to minimize additional injuries to the lung. however, increased right ventricular (rv) afterload resulting from ards could be enhanced by hypercapnic acidosis resulting from ventilation at lower tidal volume. relative contribution of these factors (ards and plv) in rv afterload is not clearly established. the aim of this study was to compare rv afterload in ards combined with plv to rv afterload in plv alone. patients and methods: this study was performed in an experimental model of severe hypercapnic acidosis performed in series of pigs. in both groups, respiratory tidal volume was decreased by %. in the first group (ards group), an ards (obtained by repeated bronchoalveolar lavage) was performed before reducing ventilation, while in the second group (control group), hypercapnic acidosis was resulting from low tidal volume ventilation alone. results: in both groups, systolic pulmonary artery pressure (paps) significantly increased during plv. this increase was significantly higher in ards group than in control group (fig. ) . severe hypercapnic acidosis occurred in both groups: paco increased from . ± . to . ± . (p < . ) and arterial ph decreased from . ± . to . ± . (p < . ) in ards group while paco increased from . ± . to . ± . (p < . ) and arterial ph decreased from . ± . to . ± . (p < . ) in control group. pao significantly decreased in ards group ( ± to ± . mmhg, p < . ) but did not significantly changed in control group. conclusion: isolated hypercapnic acidosis resulting from plv was clearly responsible for increased rv afterload and this effect was significantly enhanced in ards. pulmonary vasoconstriction resulting from hypercapnic acidosis is strongly enhanced by factors like hypoxia, endothelial injuries or inflammatory mediators in ards. extracorporeal co removal could be the solution to limit afterload burden on the right ventricle when plv is achieved during ards. introduction: prone positioning has been shown to improve mortality in acute respiratory distress syndrome (ards) patients. the respiratory system driving-pressure (dprs) and the transpulmonary driving-pressure (dpl), measured with esophageal manometry, have been shown to be strongly correlated with mortality. the aim of this study was to investigate the evolution of the dpl during prone positioning and its relationship with evolution of oxygenation in ards patients. patients and methods: ten patients with ards equipped with esophageal manometry were enrolled. dprs, dpl and chest wall driving-pressure (dpcw) were measured before and h after prone positioning. respiratory system, pulmonary and chest wall elastance (ers, el, ecw) were calculated at the same time. finally, we studied the correlation between these respiratory variables and oxygenation indicators. patients were classified as responders to prone positioning if the change in the ratio of arterial oxygen partial pressure oxygen inspired fraction (delta.pao /fio ) induced by the manoeuvre was larger than the median value observed in the group. results: in the whole population, median value of delta.pao /fio was . mmhg, and patients were classified as responders and as non-responders. in responders, dpl significantly decreased from . ± . cm h o to . ± . cm h o (p = . ) and el decreased from . ± . cm h o l to . ± . cm h o l (p = . ) after prone positioning. other respiratory variables did not change. in non-responders, respiratory variables did not change. between responders and nonresponders, there was no significant difference between baseline respiratory variables. after prone positioning, delta.pao /fio was not related to baseline respiratory parameters. on the contrary delta. pao /fio induced by prone positioning was strongly correlated with changes in dpl (r = − . , p = . ) and changes in el (r = − . , p = . ). we did not find any correlation between delta.pao /fio and changes in dpcw or changes in ecw. the correlation between delta.pao /fio and changes in dprs (r = − . , p = . ) and changes in ers (r = − . , p = . ) did not reach significance. conclusion: in patients who respond to prone positioning by the highest improvement in oxygenation, dpl significantly decrease after prone positioning. the changes in dpl and the changes in el play a major role in the improvement in oxygenation induced by prone positioning whereas the changes in dpcw and ecw do not. introduction: whereas prone positioning (pp) has been shown to improve patient survival in moderate to severe ards patients, its rate of use was . % in lung safe study. however, lung safe study was not specifically focused on pp. therefore, present study aimed to determine prevalence of use of pp in ards patients (primary endpoint), physiologic effects of and reasons for not using pp (secondary end-points). the apronet study was a prospective international one-day prevalence study performed times in april, july, october and january . at each study day, investigators had to screen every patient staying in icu from to h and to fill electronic crf. for patients with ards (defined from the berlin definition criteria) at each study day oxygenation and ventilator settings were recorded. for those receiving pp these variables were recorded before and at the end of pp session. the reasons for not proning were also collected. values are presented as median ( st- rd quartiles). prevalence rates of pp were compared by using chi square for trend and groups were compared with nonparametric tests. introduction: although acute respiratory distress syndrome (ards) has been largely focused on, few data are available concerning hypoxemia independently of its cause in intensive care unit (icu) patients. a recent prevalence-point-day (ppd) evaluated the patterns and outcomes of hypoxemia in french speaking icus. here, we describe the main etiologies, management and outcomes of the patients of this cohort presenting with severe hypoxemia. patients and methods: a ppd was conducted among french speaking icus during spring . hypoxemia was defined by a pao fio ratio below . we analyzed the data from patients with severe hypoxemia (i.e. with a pao fio ratio < ) and compared their characteristics (causes of hypoxemia, ventilatory and non-ventilatory management) and outcomes to the patients with mild or moderate hypoxemia. results: among the hypoxemic patients the day of the study, ( %) had severe hypoxemia. the main cause of hypoxemia was pneumonia and this diagnosis was more frequent than in mild and moderate hypoxemia. whereas bilateral radiologic infiltrates were present in ( . %) patients, ards was diagnosed by physicians in only ( . %) of them. invasive mechanical ventilation (mv) was used in ( . %) patients. high flow oxygen was administered in ( . %) of them and ( . %) were under non-invasive ventilation (niv) the day of the study. median vt was . ( . - . ) ml kg of ibw. positive end-expiratory pressure (peep) was higher than in mild and moderate hypoxemic patients ( ( - ) vs. ( - ) and ( - ) cm h o respectively, p < . ). median plateau pressure was . ( - . ) and was higher than in mild and moderate groups. median driving pressure was ( - ) cm h o with no difference when compared to other groups. neuromuscular blocking agents were administered in ( . %) patients, inhaled nitric oxide (ino) in ( %) patients and only patients ( . %) were on prone positioning. fourteen ( . %) patients were under extracorporeal membrane oxygenation (ecmo). icu mortality was higher in severe hypoxemic patients as compared to mild and moderate ( . vs. . and . % respectively, p < . ). icu length of stay in icu survivors was not statistically different between groups. conclusion: severe hypoxemia, independently from ards, worsens the prognosis of icu patients. even though ards might be underdiagnosed, a protective ventilation was respected in severe hypoxemic patients. introduction: major changes in septic shock management raise the questions of the relevance of the classical risk factors of nosocomial infections in the current era and the link with the primary infectious insult. we herein investigated the risk factors and the outcomes of icuacquired infections in a recent cohort of septic shock patients. patients and methods: this was a -year ( - ) monocenter retrospective study. all adult patients diagnosed for septic shock within the first h were included. septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. patients who survived the first three days were eligible for assessment of the risk of the first icu-acquired infections. the diagnosis of nosocomial infections were based on current international guidelines. patients were classified according to the development of pulmonary or non-pulmonary icu-acquired infections. the determinants of icu-acquired infections were addressed in a multivariate logistic regression analysis. results: patients were admitted for septic shock. patients remained alive in the icu after the first three days and could then be evaluated for the risk of icu-acquired infections. hence, patients remained free of secondary infections, patients first developed an episode of nosocomial pneumonia and patients first developed an episode of non-pulmonary infection. the mortality rates of patients with icu-acquired pneumonia, non-pulmonary icu-acquired infections and without secondary infections were , and %, respectively (p = . ). in multivariate analysis, the development of icu-acquired pneumonia was independently associated with male gender (or . , ci % [ . - . ], p = . ), renal replacement therapy (or . , ci % [ . - . ], p = . ), platelet transfusion (or . , ci % [ . - . ], p = . ) and a primary pulmonary infection (or . , ci % [ . - . ], p < . ). the development of non-pulmonary infections was independently associated with renal replacement therapy (or . , ci % [ . - . ], p < . ), fresh frozen plasma transfusion (or . , ci % [ . - . ] , p = . ), healthcare-associated septic shock (or . , ci % [ . - . ], p = . ). conclusion: icu-acquired pneumonia occurs preferentially in patients with septic shock of pulmonary origin. in addition, we identified the transfusion of blood products as a risk factor for pulmonary and nonpulmonary nosocomial infections. introduction: human serum albumin is used for the restoration of blood volume, emergency treatment of septic shock patients. several experimental studies suggested that albumin could have additional protective effects on the vascular wall and more specifically on endothelial functions. however, the in vivo effect of albumin in human endothelium remains unknown. the aim of this study is to assess the effect of albumin or saline infusion on skin endothelial function in septic shock patients requiring volume expansion. we performed a prospective randomized monocentric study in an -bed medical intensive care unit. all patients with septic shock who required fluid administration were included between h and h after vasopressor starting. patients were randomized to receive either ml of saline solution . % or ml of albumin %. norepinephrine dose was not modified h before and during the procedure. endothelium-dependant vasodilatation in the skin circulation was assessed by iontophoresis of acetylcholine before and after fluid administration. the improvement of skin blood flow in response to acetylcholine after fluid administration was compared between groups. for each patient, age, sex, saps ii, site of infection, global hemodynamic parameters and clinical microcirculatory parameters were recorded. results are expressed as mean ± sd. qualitative data were compared using chi- or fisher's exact test while quantitative data comparisons used student t test or mann-whitney as appropriate. results: twenty-two patients were included ( women, age: ± , saps ii: ± ). twelve patients received saline and received albumin. apart from age, no statistical difference was found between groups regarding demographic characteristics and baseline hemodynamic parameters. norepinephrine dose and mean volume of infused fluid before inclusion was not different between groups (table ) . before fluid replacement, endothelial response to acetylcholine iontophoresis was not different between groups (auc vs ; p = . ). volume expansion induced a slight increase of systolic arterial pressure, significantly higher in the albumin group ( vs %; p = . ) with no difference regarding cardiac output variations between groups. next, we compared the variations of endothelium response to iontophoresis before and after fluid infusion. the improvement of endothelial response after acetylcholine challenge was significantly higher in the albumin group ( vs %, p = . ). conclusion: in the early stage of septic shock resuscitation, we showed that albumin infusion had protective endothelial effects. this result has to be confirmed in a larger cohort. ] + all p < . ). we found no correlation between cognitive scores at hospital discharge and the severity of eeg-defined encephalopathy during the days of icu or during the first h after admission. however, sepsis survivors' scores were lower than controls' (p < . ) ( table ) . conclusion: in this study, eeg was more sensitive than clinical tools to detect sae but clinical scales correlated with the eeg grade. encephalopathy was not associated with short-term cognitive function. further study and a larger cohort are needed to determine which early eeg introduction: there is growing evidence that corticotherapy improves survival from septic shock. this observational study aimed at evaluating at bedside resistance to corticosteroids in adults with sepsis. patients and methods: participants-icu adults with septic shock or without sepsis admitted to the raymond poincaré university hospital. we also evaluated healthy controls. intervention-resistance to corticosteroids was assessed using a skin test. µl of dermocorticoid cream (class iii, betamethasone) was applied on a cm surface of the skin. at h, two independent physicians scored the blanching of the skin from to - -no blanching + -< % of surface + - to % of surface + - to % of surface, and -blanching beyond application area. cohen's kappa was used to measure concordance. a mean score of < indicated corticoresistance and a score of indicating normal sensitivity to corticosteroids. we also performed a µg acth test. results: we enrolled patients, patients with septic shock ( males, ) and patients without sepsis ( males, ). overall, ( %) with two measurements patients had concordant evaluation of score by the two physicians + while had a difference of -point in scores, resulting in a kappa of . ( % ci . - . ). in patients with septic shock, ( %) have corticoresistance, i.e. a mean score < , ( %) a score of or , and ( %) has normal sensitivity to corticosteroids. in non-septic critically ill, ( %) have corticoresistance, ( %) a mean score of - , and ( %) have normal sensitivity to corticosteroids. hence, as compared to non-septic patients, patients with septic shock were more likely to have corticoresistance (p = . ). discussion: topic application of corticosteroids on the skin results in activation of glucocorticoid receptors present within the vessels. subsequently, activation of lipocortin may inhibit the activity of phospholipase a , regulator of prostaglandins, leucotrienes and platelet activating factor. then, the coupling of alpha adrenoreceptors to their agonists is potentiated, increasing vessels smooth muscles sensitivity to catecholamines. the subsequent local vasocontriction is reflected by skin blanching. thus, the observed lack of skin blanching in septic patients may reflect altered coupling between gluocorticoids and glucocorticoids receptors. conclusion: roughly one out of two adults with septic shock may develop a resistance to corticosteroids as assessed by a skin blanching test in response to betamethasone. introduction: mild therapeutic hypothermia, currently recommended in the management of cardiac arrests with shockable rhythm could promote infectious complications and especially ventilator-associated pneumonia (vap) (mongardon et al. crit care med ). despite high incidence of vap and retrospective trials suggesting a benefit of shortterm ( h) antibiotics in this setting (davies et al. resuscitation ) , systematic use of antibiotic prophylaxis is not recommended in patients treated with mild therapeutic hypothermia after cardiac arrest. the primary objective was to demonstrate that systematic short-term antibiotic prophylaxis with amoxicillin-clavulanic acid can reduce incidence of early vap (< days) in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest. secondary objectives were its impact on incidence of late vap and on day mortality. patients and methods: multicenter two parallel-group doubleblinded randomized trial. adult patients hospitalized in icu, mechanically ventilated after out-of-hospital resuscitated cardiac arrest related to initial shockable rhythm and treated with mild therapeutic hypothermia were eligible. exclusion criteria were pregnancy, need for extracorporeal life support, ongoing antibiotic therapy or pneumonia, known chronic colonization with multiresistant bacteria, known allergy to beta-lactam antibiotics and moribund patients. patients received either intravenous injection of amoxicillin-clavulanic acid ( g mg) or placebo three times a day for days. the primary endpoint was the onset of early vap. all suspected pulmonary infections were adjudicated by a blinded independent committee. results: out of patients included, were finally analyzed, in treatment group and in placebo group (mean age . ± . years, sex ratio = , sofa score . ± . ). characteristics of cardiac arrest were similar in both groups (no flow = . ± . min vs . ± . min, low-flow = . ± . min vs . ± . min). early vap were confirmed, in treatment group vs in placebo group, with an incidence of . vs . %, respectively (hr = . + ic % = [ . + . ], p = . ) (fig. ). the procedure did not affect occurrence of late vap (> days), respectively vs . day mortality was similar in both arms ( . vs . %, p = . ) and no adverse event was related to study treatment. conclusion: short-term antibiotic prophylaxis with amoxicillin-clavulanic acid significantly decreases incidence of early vap in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest related to shockable rhythm. introduction: immunosuppressed (is) patients are prone to develop respiratory failure and to need ventilatory support. invasive ventilation shared a grim prognosis in the past and non-invasive ventilation had been recommended in these patients, however niv efficacy has been recently challenged and the advent of high flow oxygen therapy had brought even more complexity in the management of such patients. using the data from a recent point-prevalence-day of hypoxemia in icu, we compare the frequency, management and outcomes of hypoxemia in is and immuncompetent (ic) patients. patients and methods: the spectrum study was conducted in french-speaking icus in countries during spring . is was retained in case of malignant hemopathy, hiv positivity, immunosuppressive drugs, recent chemotherapy, neutrophil count < . g l. hypoxemia was defined as a pao fio ratio > and separate into severe (> ), moderate (> ) and mild (> ). we focused on the causes of hypoxemia, the ventilatory management and the outcome. results: among the patients included, ( %) were is out of whom ( %) were hypoxemic, proportion similar to the ic patients. mean age and igs- of hypoxemic patients were similar in is and ic patients. hypoxemia was mild in ( %), moderate in ( %) and severe in ( %) is patients with a similar distribution compared to hypoxemic ic patients. the causes of hypoxemia were also similar pneumonia being the leading cause. ( %) hypoxemic is patients fulfilled the berlin criteria for ards in a similar proportion to ic patients. respiratory support used in hypoxemic is patients was ambient air in , low flow oxygen in , high flow in , niv in and invasive ventilation in patients, with a different distribution from the ic patients (more patients on high flow therapy and less invasively ventilated). the day of the study, thoracic ct scan and echocardiography were performed in a similar proportion in is and ic patients whereas broncho-alveolar lavage was more frequently performed in is patients ( vs %, p < . ). finally, as expected, icu mortality was higher in hypoxemic is patients ( vs %, p < . ). conclusion: immunosuppression in the icu seems not to be associated with hypoxemia, severity of hypoxemia or ards. oxygenation management is slightly different from immunocompetent patients with more frequent use of high flow therapy. ( ) mmhg, ph . ( . ). were included in the l/kg/min group and in the l/kg/min group. no difference was observed between groups for baseline characteristics. failure rate was not different between groups- . vs . % + p = . . no center effect was observed for failure. discomfort was more frequent in the l kg min group- vs % + p = . . the length of stay was shorter in the l kg min group- . ( . ) vs . ( ) days + p = . . intubation occurred in patients in the l/kg/min group vs patients in the l kg min group (p = . ). conclusion: hfnc with a flow rate of l/kg/min did not reduce the risk of failure compared to l/kg/min at the initial respiratory management of avb in young infants. comparison of epinephrine and norepinephrine for the treatment of cardiogenic shock following acute myocardial infarction. optima cc study levy bruno introduction: despite the frequent use of vasopressors which are administered in % of patients in cardiogenic shock (cs), there is only limited evidence from randomized trials comparing vasopressor in cs. hence, the optima cc study was designed to compare epinephrine and norepinephrine in cardiogenic shock following myocardial infarction. patients and methods: multicenter, double-blind, randomized trial in french icu. cardiogenic shock patients due to myocardial infarction treated by pci were randomized to receive epinephrine or norepinephrine to maintain map at mmhg. dobutamine was introduced at the physician discretion according to a combination of parameters-echocardiographic parameters, cardiac index, lactate clearance, svo and swan-ganz derived parameters. results: / patients were ventilated ( %). there were no differences in the duration nor in the maximal dose or cumulated dose of epinephrine or norepinephrine. dobutamine was used in / ( %) in the epinephrine group and in / ( %) in the norepinephrine group. there were no differences in the duration, in the maximal or cumulated dose. arterial pressure evolution was similar. heart rate increased significantly in epinephrine group and did not change in norepinephrine group. cardiac index and cardiac power index increased significantly more in the epinephrine group than in the norepinephrine group. cardiac double product, a surrogate of myocardial oxygen consumption increased in epinephrine group and did not change in norepinephrine group. epinephrine use was associated with a lactic acidosis from h to h while arterial ph increased and lactate level decreased in norepinephrine groupepinephrine was significantly associated with an higher incidence of refractory shock- / ( %) versus / ( %) p = . ). the incidence of arrhythmia was identical (epinephrine- % versus norepinephrine- %, p = . ). ecmo was used in / ( %) in the epinephrine group and in / ( %) in the norepinephrine group (p = . ) mortality was / ( %) in the norepinephrine group and / ( %) in the epinephrine group (p = . ) epinephrine use was associated with a trend to an increased risk of death (p = . ) and an increased risk of death plus ecmo (p = . ) at days. there was a trend for an increased risk of death plus ecmo at j (p = . ). conclusion: in patients with cardiogenic shock following myocardial infarction, epinephrine use was associated with a lactic acidosis, an higher incidence of refractory shock and an increased risk of death plus ecmo at j . high dose immunoglobulins in toxic shock syndrome in children: a pilot randomized controlled study (ighn study) javouhey etienne , leteurtre stéphane , tissières pierre , joram nicolas , wroblewski isabelle , ginhoux tiphanie , dauger stéphane , kassai behrouz hôpital mère enfant, bron, france; hôpital jeanne de flandre, lille, france; hôpital du kremlin-bicêtre, le kremlin-bicêtre, france; chu nantes, nantes, france; chu grenoble, la tronche, france; hospices civils de lyon, bron, france; hôpital robert debré, paris, france; hospices civils de lyon, bron, france correspondence: javouhey etienne -etienne.javouhey@chu-lyon.fr annals of intensive care , (suppl ):co- introduction: superantigen toxins synthesized by s. aureus or by s. pyogenes are responsible for toxic shock syndromes (tss) which lethality can reach %. high dose intravenous immunoglobulins (ivig), able to neutralize these toxins, are frequently used even tough evidence of its efficacy is not supported by randomized controlled study (rct) . moreover, ivig are expensive and possibly harmful. before conducting a rct, a pilot study was first designed to assess the feasibility in the context of pediatric critical care. patients and methods: a double blinded rct was performed comparing g kg of ivig to isovolumic % albumin perfusion within the first h of tss in children aged between month to years. a priori criteria to determine the feasibility were defined as a rate of inclusion among eligible patients > %, a rate of protocol's deviations < % (treatment delivery, non-respect of blinding, premature stop), and by the practical and financial aspects of the protocol. secondary objectives were to assess the efficacy of ivig on organ dysfunction (using pelod- score), on mortality at day and their safety. the study was promoted by the hospices civils of lyon, approved by the cpp sud-est and registered at clinical trial (nct ). inform consent from both parents was required before randomization. this study was funded by csl-behring company. results: during the months study period, patients were included in centers. the inclusion rate was of % ( parent's refusals, parents were absent at admission). two patients were wrongly included (pneumococcal shocks), one patient didn't receive the treatment because he was transferred for ecmo in a non-investigator center, three patients were treated after h, and in two patients one bottle of treatment was missing. the blinding was well respected. missing data on the pelod score and mortality was lower than %, and no premature stop was reported. the ecrf completion was judged easy by investigators. the inclusion of children within the first h was judged challenging. the treatment delivery had to be improved, requiring the help of research assistants. seven serious and one severe adverse events were registered, all patients recovered and no death was reported. conclusion: this pilot study suggested that a rct is feasible. it provides crucial information to improve the recruitment, the respect of the protocol and the correct measure of organ failure. however, inclusion of international centers is necessary to attain the sample size required. indirect calorimetry-based method for the work of breathing assessment when compared to esophageal pressure (pes) measurement and electrical activity of the diaphragm (eadi) during a spontaneous breathing trial in continuous positive airway pressure. patients and methods: a prospective single center study. all intubated and mechanically ventilated children > months and < years old, hospitalized in the pediatric intensive care unit were eligible. patients considered as ready to extubate were included. simultaneous recordings of vo , pes and eadi were performed during steps: before, during and after the spontaneous breathing test in continuous positive airway pressure. results: twenty patients, median . months, were included. half of the patients were admitted for a respiratory reason. predicted resting energy expenditure was overestimated as compared to measured resting energy expenditure ( [ - ] vs [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] kcal kg day, p < . ). spontaneous breathing test was associated with an increase in esophageal pressure-time product from to cm h o s min. the same trend was observed in respiratory drive, assessed by eadi which increased from . [ . - . ] to . [ . - . ] . oxygen consumption obtained by ic was higher during spontaneous breathing test as compared to conventional ventilation ( . [ . - . ] vs . [ . - . ] ml kg min) but non significantly. changes in work of breathing as assessed by vo was poorly correlated with measurements from pes and eadi whereas we found a moderate correlation between pes and eadi values. spontaneous breathing test and extubation were successful in ( %) and ( %) patients, respectively. conclusion: during weaning from mechanical ventilation, spontaneous breathing test in continuous positive airway pressure induced an increase in work of breathing, both in respiratory drive, as measured by eadi and in respiratory mechanics, as measured by pes. oxygen consumption measured by indirect calorimetry does not seem to be a reliable tool to assess work of breathing in mechanically ventilated children. ben gheriba khalil , grimaud marion , heilbronner claire , roy emeline , hadchouel alice , renolleau sylvain , rigourd virginie hôpital necker enfants malades, paris, france correspondence: ben gheriba khalil -bg.khalil@gmail.com annals of intensive care , (suppl ): introduction: during the winter season - we had evaluated breastfeeding disruption after hospitalization for bronchiolitis in our hospital in infants under month (n = ). we observed % of mothers whose breastfeeding was stopped of modified. clinical severity had no impact on breastfeeding but % of mothers stated that lack of support and advice was the first cause of breastfeeding disturbance. we conducted this second phase to evaluate the potential impact of actions to promote breastfeeding on unwanted weaning during hospitalization for bronchiolitis. patients and methods: this is a cross sectional study during two epidemic seasons of bronchiolitis in a tertiary care hospital. all patients aged months or younger hospitalized with acute bronchiolitis and receiving at least partial breastfeeding were eligible for the study. patients discharged at home whose parents accepted to be contacted by phone were included. a bundle of actions to promote breastfeeding in patients with bronchiolitis was implemented (posters, flyers, staff training, equipment with breast pumps) between the two epidemic seasons. the data was extracted from the charts and from a phone survey two weeks after discharge to evaluate breastfeeding in eligible patients in our hospital. phase i (before action) had included patients hospitalized between december and march in all wards hosting patients with bronchiolitis. phase ii (after action) included patients hospitalized from october to december . the data from phase ii was compared with data from phase i. results: fifty patients could be included during the second step of the study, with a mean age of days. breastfeeding was exclusive for % of mothers (vs % in phase i). the median length of stay was days (vs days in phase i). twenty-one ( %) patients spent time in picu vs. % in phase i, needed intubation, received non invasive ventilation for a median length of days (vs. days in phase i). the number of patients needing nutritional support was ( %) during phase ii vs. ( %) during phase i. after implementation of our actions, ( %) mothers kept breastfeeding as before (vs. % in the previous epidemic season, p < . ), mothers ( %) stopped, ( %) switched to partial breastfeeding and ( %) reduced without stopping. conclusion: bronchiolitis is a high risk event for breastfeeding disruption but staff training and correct advices and support for mothers during hospitalization seems to diminish that risk. benefits of using a high temporal resolution database in the automatic real-time pediatric ards screening nardi nicolas introduction: pediatric acute respiratory distress syndrome (pards) is frequent in pediatric intensive care units (picu), potentially lethal and the diagnosis is often missed or delayed (palicc ) . in picu, data are usually recorded between to min which leads to only a minority of the arterial partial pressure of oxygen (pao ) that are usable to calculate a valid oxygenation index (oi). if not available, pao should be replaced by the spo if < % to calculate the oxygen saturation index (osi). using a high temporal resolution (htr) database that records data every - s, we aim to develop a relevant clinical algorithm of mass data aggregation to improve pards screening with the automatic oi and osi calculation. patients and methods: all the patients admitted to our pediatric icu between may and august were included. the htr and the electronic medical records (emr) were queried through structured query language (sql) following these steps-( ) data selection ( ) extraction to a linear format ( ) date and time synchronization ( ) data pivoting ( ) aggregation through a -min moving average ( ) hypoxemia calculation. statistical analysis included proportions, correlations and bland-altman analysis. results: between may and august , patients ( stays) were admitted to the picu. approximately million rows were retrieved from the databases including , pao values. the algorithm was able to calculate , ( % of the pao ) oi and osi. the comparison between oi and osi showed that . % of the results were between the limits of agreements (− . + . ), a bias of − . and a correlation r = . . the comparison between the ois from the htr and emr databases showed that . % of the results were between the limits of agreements (− . + . ), a bias of − . and r = . . conclusion: using a mass data aggregation algorithm on a htr database allows more pao to be used to calculate an oi than the usual emr. the oi results differ slightly between the htr and the emr. the accuracy is probably in favor of the htr because of the shorter timelapse between the oi parameters. the osi is possibly a biased oi surrogate and should be interpreted with caution. our next step will be to measure the impact of the algorithm on the pards real-time diagnosis and pards severity categories. introduction: early administration of appropriate antibiotic therapy with adequate concentration is the cornerstone of the severe sepsis and septic shock's treatment. adult studies showed alteration of distribution and elimination which can lead to insufficient drug concentration in septic patients. in children, studies are lacking and antibiotic dosing may be suboptimal. we aim to describe the plasma concentration of the most used beta-lactam in critically ill children, to describe the rate of patients with suboptimal exposure and associating clinical and biological factors. patients and methods: this was a prospective, single center, observational study designed in beds pediatric intensive care unit (picu) and high dependency care at the necker hospital (paris, france) from january to may . were included, children with severe sepsis or septic shock, aged less than years and weighing more than . kg, and receiving one or more of the following antibiotics-amoxicillin, cefotaxime, cefazolin, ceftazidime, piperacillin-tazobactam, meropenem and imipenem for suspected or proven infection. betalactam plasma concentrations were analysed using high performance liquid chromatography. results: we enrolled children (severe sepsis, n = ( . %) + septic shock, n = ( . %)) with a median age of months ( - . bacteria were identified in patients ( . %). a total of blood samples were analysed at a median of days ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) following the onset of sepsis. twenty-four patients ( . %) had insufficient concentration (cefotaxime ( %) + piperacillin-tazobactam, ( %) + amoxicillin ( %) + meropenem ( %), cefazoline ( %), imipenem ( %) + ceftazidime ( %)). insufficient concentrations were associated with early measurements (< h from the sepsis' onset) (p = . ) and creatinine clearance increase (p = . ). adequate concentrations were associated with small age (p = . ). in conclusion, current standard beta-lactam dosing in children with severe sepsis or septic shock could be inadequate to reach the target concentrations. that could lead to the risk of clinical and bacteriological failures as well as the emergence of bacterial resistance. further pharmacokinetic studies are mandatory to improve antibiotic therapy in this vulnerable population. introduction: intermittent hemodialysis is a key support therapy in icu. despite protocol-based optimization, intradialytic hemodynamic instability (ihi) remains a common complication and could account for mortality and delayed renal recovery. the identification of patients at high risk for ihi is crucial but remains poorly explored. our objective was to test whether tissue perfusion parameters assessed at the bedside (mottling, index capillary refill time (icrt), and lactate) predict ihi and to develop and to validate a predictive score of ihi. patients and methods: prospective observational study in a -bed medical icu in a tertiary university hospital including hemodialysis sessions performed for acute kidney injury. exclusion criteria were patients with dark skin and dialysis performed in extreme emergency. mean arterial pressure (map), mottling score, icrt, and lactate were recorded just before starting hemodialysis. first episode of ihi requiring therapeutic intervention was recorded , , and min after hemodialysis starting. results: ninety-six hemodialysis sessions performed in patients were recorded. half of the patients received vasopressors (n = , %). ihi occurred in ( %) sessions and was more frequent among patients receiving vasopressors ( vs %, p < . ). mottling were more frequent ( vs %, p = . ), lactate levels higher ( . [ . - . ] vs . [ . - . ] mmol l, p < . ) and icrt longer ( . [ . - . ] vs . [ . - . ] s, p < . ) before sessions with ihi compared to sessions without, independently of map (p < . ). the incidence of ihi increased with the number of tissue perfusion alterations ( , , , and % for , , , and alterations, respectively, p < . ). a tissue hypoperfusion score, defined as icrt (seconds) + lactate level (mmol l) + if mottling presence was predictive of ihi independently of map (or . [ . - . introduction: epidemiological data suggest an increased risk of longterm chronic kidney disease after acute kidney injury (aki). in survivors of out-of-hospital cardiac arrest (ohca), aki is frequent and is associated with numerous factors of definitive renal injury. we made the hypothesis that aki after ohca was a strong risk factor of long-term chronic kidney disease (ckd). we aimed to evaluate renal outcome of ohca survivors according the occurrence of aki in icu. patients and methods: we used the cohort of consecutive ohca patients admitted between and in a tertiary medical icu previously described (geri et al. icm. ) . aki was defined by kidney disease improving global outcomes (kdigo) criteria. long-term creatinine level was the last blood creatinine assessment we were able to retrieve. the main outcome was the occurrence of ckd, defined by an estimated glomerular filtration rate (egfr) lower than ml min . m according to the mdrd equation. long-term mortality was evaluated as well. factors associated with ckd occurrence were evaluated by competing risk survival analysis (fine gray and cox cause specific models providing sub-hazard ratio (shr) and cox sub-hazard (csh)). results: among the ohca patients who were discharged alive, we were able to retrieve the outcome of patients (median age [iqr , ] , . % of male) who were included in the analysis. during a median follow-up time of . [ . - . ] years, ckd occurred in ( . %) patients and ( %) patients died. a previous history of arterial hypertension (shr = . [ . + . ], p = . + csh = . [ . + . ], p = . ), aki during icu stay (shr = . [ . + . ], p = . + csh = . [ . + . ] , p = . ) and an age higher than (shr = . [ . + . ] , p = . + csh = . [ . + . ], p = . ) were independently associated with ckd occurrence. aki was not associated with long-term mortality (shr = . [ . + . ], p = . + csh = . [ . + . ], p = . ). in ohca survivors resuscitated from an ohca, ckd was a frequent long-term complication. aki during icu stay was a strong determinant of long-term ckd occurrence. introduction: many critically ill patients have a moderate to high risk of bleeding but they also require prolonged intermittent dialysis to ensure a negative water balance without hemodynamic adverse events. thus, a heparin-free easy-to-use anticoagulation within the dialysis circuit is needed but, to date, usual protocols (iterative saline flushes, heparin grafted membranes) lead to - % of premature clotting and sessions that last greater than min are rarely achievable. we assessed the safety and efficiency of heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance (an online measure of the instantaneous clearance of small molecules available in most of dialyzers). patients and methods: we prospectively reported the clotting events that occurred during all the heparin-free dialysis sessions that were performed with a regional anticoagulation based on calcium-zero citrate-containing dialysate (citrasate, hemotech, france) between january and august in a -beds icu. results: a total of dialysis sessions were performed in patients (mechanical ventilation n = + norepinephrine n = ). median duration of dialysis was min (iqr, - + maximum min), and median ultrafiltration volume was l (iqr . - . ). when assessed, urea and beta -microglobulin reduction rates were . % ± . % and % ± . %, respectively. postfilter ionized calcium was . ± . and . ± . mmol l at and h, respectively, within the extracorporeal circuit. a major clotting event that led to premature termination of the session occurred in only sessions ( . %) . in these five cases, major catheter dysfunction occurred before clotting within the circuit. prefilter ionized calcium remained within narrow ranges (before after change + . ± . mmol l), and total-to-ionized calcium ratio, a surrogate marker for citratemia, was unchanged and always below . . in sessions, no ionized calcium measurement was required. conclusion: dialysis anticoagulation with calcium-free citrate containing dialysate is an easy-to-use, efficient, and inexpensive form of heparin-free regional anticoagulation. calcium reinjection according to ionic dialysance allows prolonged hemodialysis sessions in critically ill patients without the need to systemically monitor ionized calcium. sessions can be safely extended according to the hemodynamic tolerance to ensure an adequate dose of dialysis and a negative water balance, a major point in patients with severe aki. introduction: brain injury is the first cause of death after cardiac arrest (ca) and multimodal neuroprognostication is a cornerstone of postresuscitation care. among the different usable information provide by electroencephalogram (eeg), the aim of this study was to evaluate the predictive value of eeg reactivity regarding neurological outcome at discharge. patients and methods: using our prospective registry of successfully resuscitated patients admitted to a cardiac arrest center between january and , we studied all consecutive comatose patients still alive at h and in whom at least one eeg was performed during coma. in addition to usual clinical findings, we collected eeg (patterns and reactivity, status epilepticus) and somatosensory evoked potentials characteristics. the eeg reactivity was evaluated by a blinded neurophysiologist and was defined as a reproducible change of the tracing (in amplitude or frequency) provoked by an auditory and a nociceptive standardized stimulation. we evaluated the predictive values of persistent lack eeg reactivity and other indicators regarding their respective ability to predict a favorable or unfavorable outcome. recovery of a level or on the cerebral performance category (cpc) scale at discharge was considered as a favorable outcome, as opposed to recovery of a cpc level - (unfavorable outcome). we included patients who were mostly male ( %), with median age of years. ca occurred in a public place in % of cases, and it was witnessed in % of cases. bystander cpr was initiated in % patients and the initial cardiac rhythm was shockable in % patients. median time to eeg was days ( - ) and % of patients were still sedated during the examination. a favorable neurologic outcome was observed in patients ( %). an eeg reactivity was present in patients ( %) with favorable outcome and in patients ( %) with unfavorable outcome. the positive predictive value (ppv) of a persistent eeg reactivity for prediction of favorable outcome was % . by contrast, the ppv of lost eeg reactivity for prediction of unfavorable outcome was % (ic % - ) with a false positive rate (frp) of . % ( . - . ). eeg electroencephalogram, ssep short-latency somatosensory evoked potentials, ppv positive predictive value, npv negative predictive value, fpr false positive rate in this population of post-cardiac arrest patients, the presence of eeg reactivity was poorly predictive of a favorable neurologic outcome. the absence of reactivity was highly predictive of unfavorable outcome. in combination with other indicators, searching for eeg reactivity may have important implications in the neuroprognostication process. conclusion: this subgroup analyses of a randomized controlled trial, found no survival benefit when comparing crystalloids to colloids in critically ill surgical patients. introduction: goal of a fluid challenge (fc) is in fine to increase the stroke volume (sv) or the cardiac index (ci) when an episode of hypovolemia or a preload dependence status are suspected. fc is one of the most common practices in icus, however, the way to assess the response to fc is not standardized. the present study aimed to evaluate whether the trans-thoracic echocardiographic (tte) assessment of the response to fc immediately at the end of the infusion or delayed min later could affect the results of the fc. patients and methods: prospective, observational, multicentre study including all icu patients in septic shock requiring a fc. were excluded patients with-arrhythmias, poor echogenicity and severe mitral or aortic regurgitation. fc was performed administering ml of crystalloids over min. fluid responsiveness was defined as a > % increase in stroke volume (sv). the following echocardiographic parameters were recorded-e wave, a wave, e a ratio, velocity-time integral (vti), ea wave and sa wave. map, hr and tte variables were collected at baseline (t ), at the end of fluid challenge (t ) and (t ) and min (t ) after the end of fluid challenge. quantitative data are expressed as mean and standard deviation (sd) or median and interquartile (iqr), according to their distribution. qualitative data are expressed as absolute number and frequency (%). results: from may th to january th , a total of patients were enrolled in french icus (mean age- ± years, median igs ii- , median sofa score- [ ] [ ] [ ] [ ] [ ] ). among the ( %) patients responders to fc at t , patients were transient responders (tr), i.e. became non-responders at t ( %, % ci = [ - ]) and ( %, % ci = [ - ])) patients were persistent responders (pr), i.e. remained responders at t . among the non-responders (nr) at t , became responders at t , ( %, % ci = [ . - . ] ). in the subgroup analysis, no statistical difference in haemodynamic and echocardiographic parameters was found between non-responders, transient responders and persistent responders (fig. ) . conclusion: the present study shows that, after a % vti increase at the end of the fc, vti returns to baseline at min in half of the responders. blood volume status (normo or hypovolemia) before initiating the fluid infusion could explain the transient or persistent response to fc observed in septic patients. mottling score is a strong predictor of day- mortality in sepsis patients independently of catecholamine dosing and other tissue hypoperfusion parameters dumas guillaume , joffre jérémie , hariri geoffroy , bigé naike , baudel introduction: sepsis is a frequent critical condition. mottling score, an hypoperfusion parameter, is well correlated with outcome. however, uncertainties persist regarding its value not only as a marker of patient severity but also as an independent predictor of mortality and treatment efficacy. we performed a post hoc analysis of four published prospective studies including sepsis patients with or without shock. we analyzed the relationship between the mottling score (from to ) and day- mortality according to other prognosis covariates such as catecholamine dosing, urine output and plasma lactate levels. first, factors associated with outcome were determined by multivariate analysis. second, mottling score-by-covariate interaction was studied to better understand its effect on mortality. finally, effect of mottling score variation at different time point (h -h -h -h ) was assessed. whereas ecmo was successfully weaned in ( %) patients. proportion of perfused vessel (ppv), perfused vessel density (pvd), micro flow index (mfi) and heterogeneity index (hi) were severely impaired before ecmo. re-establishing high and stable peripheral blood flow with va-ecmo led to a rapid decrease in heart rate and vasoactive inotropic support and significantly improved all microcirculation parameters within h. total vessel density and pvd, measured before and after ecmo initiation, were better in patients successfully weaned from ecmo (p < . ) (fig. ) . conclusion: cardiovascular support with ecmo-va rapidly improved macro and microcirculation in refractory cardiogenic shock patients. total vessel density and perfused vessel density were significantly better in survivors h after ecmo initiation and might therefore help to predict outcomes. further studies are now needed to better define the utility of this technology in larger groups of va-ecmo patients. introduction: thyroid storm is a rare but life-threatening disease related to thyrotoxicosis. it can lead to multiple organ failure including cardiovascular disorders or neurological impairment. to date, data on this disease in icu patients are scarce and limited to case reports. we therefore aimed to describe clinical presentation, outcomes and management of thyroid storm in icu patients. patients and methods: local diagnoses coding database (from january to july ) from french icu were interrogated for main and secondary diagnoses codes including thyrotoxicosis based on the international classification of disease th revision. thereafter two investigators reviewed all the medical records selected. inclusion criteria were thyroid storm based on the diagnostic criteria of the japan thyroid association (t. satoh, endocrine journal ). it combines thyrotoxicosis with elevated levels of free triiodothyronine (ft ) or free thyroxine (ft ) with at least two of the following symptoms-central nervous system manifestation, fever, tachycardia > bpm, congestive heart failure, or total bilirubin level more than micromol/l. clinical presentation, therapy used, and outcome were recorded. results: sixty-two patients (median age years (interquartile range - ) + saps ii ( - ) were included. thyroid storm was the first manifestation of thyrotoxicosis in ( %) patients. graves' disease ( %), amiodarone induced thyroiditis ( %), autoimmune thyroiditis ( %), and toxic multinodular goitre ( %) were the main causes of hyperthyroidism. amiodarone, thyroid hormone toxicity, antithyroid drugs withdrawal or infectious trigger were identified in ( %) patients. organ support including mechanical ventilation, catecholamine infusion, renal replacement therapy and veno-arterial ecmo were used in , , , and patients, respectively. main thyroid storm treatments included antithyroid drugs ( %), betablockers ( %), corticosteroids ( %), and plasmapheresis ( %). lastly, icumortality was %, with multiple organ failure responsible of death in all patients. although its incidence appears low, icu physicians should be aware of the multiple clinical features of thyroid storm. our preliminary data reported various specific therapeutic management of this potentially fatal disease. prompt initiation of targeted therapies is required for atypical hemolytic uremic syndrome (ahus) and thrombotic thrombocytopenic purpura (ttp), but no specific therapy is consensual for shiga toxinassociated hemolytic uremic syndrome (stec-hus). thus, rapid differentiation of stec-hus is mandatory to tailor the initial treatment. furthermore, apart from large outbreaks, characteristic features of this syndrome in adults have not been described. in this study, we retrospectively compared the characteristics of stec-hus, ahus and ttp patients at admission in two expert icus. patient were included if they presented with the triad of mechanical hemolytic anemia, thrombocytopenia and organ damage, and tmas were classified using international criteria. other causes than stec-hus, ahus and ttp were excluded. results: amongst tmas admitted between september and january , stec-hus, ahus and ttp were included. stec-hus patients were older ( ) than ahus ( , p = . ) and ttp patients ( , p < . ). they presented with more frequent digestive symptoms ( versus and % for ahus and ttp, p = . and < . ), but bloody diarrhea was rare ( %) and non-statistically different from other tmas. confusion was more frequent in stec-hus ( %) than ahus patients ( %, p = . ). biologically, stec-hus patients displayed elevated fibrinogen levels ( . vs . and . for a hus and ttp, both p < . ) and severe renal failure. forty-two percent required renal replacement therapy and % were treated with plasma exchange before the distinction from other tmas could be made. only ( %) stec-hus patient died in the icu (fig. ) . conclusion: characteristics supposed to identify stec-hus are largely shared with other tmas. in particular, the differential diagnosis between ahus and stec-hus appears to be more difficult than the stereotypical description derived from pediatric studies. severe hyperglycemia in icu patients: a higher mortality rate and a higher incidence of diabetes in a long-term follow-up study . ], p = . ) but not when admitted for coma, sepsis or cardiac arrest. mortality rate was significantly higher in patients with severe hyperglycemia compared to those without, regardless of preexisting diabetes (hnd hd vs. nhnd nhd groups + p < . ). patients with severe hyperglycemia had a higher incidence of type diabetes at ( vs. % + p = . ) and months ( vs. % + p = . ) compared to those who did not. conclusion: severe hyperglycemia occurring in the first days of icu admission was associated with higher mortality rate and an increased risk of diabetes in the following months regardless of preexisting diabetes. introduction: vitamin d deficiency is frequent in northwestern countries and could represent a modifiable risk factor for critically ill patients, in relation with its pleiotropic effects ( ) . some studies reported an association between oh vitamin d ( oh) deficiency, chronic health status and icu-and hospital-related outcomes. however, a large supplementation study have not been found to improve outcome of patients with moderate oh deficiency (< ng ml) ( ) . the aim of the study is to analyze the relationship between the severity of oh deficiency at icu admission, severity of illness and outcomes and ultimately to identify subgroups of patients in whom the likelihood of benefit of supplementation is larger. patients and methods: consecutive patients admitted over a -month period who stayed at least h in a medical surgical -bed icu were included. in these patients, demographic data, charlson comorbidity score, severity scores (saps and sofa) and -oh (chemiluminescence, diasorin) were collected at admission. icu and hospital length of stay (los) and mortality were recorded. correlations were searched between oh and the different scores, and vital outcomes ( - )). hypothyroidism was unknown before icu admission in % patients. median sofa score at icu admission was ( - ). myxedema coma, circulatory failure, respiratory failure, and severe hypothermia were respectively the main admission reason in , , , and % patients. a precipitating factor such as drugs thyroid toxicity, thyroid hormone withdrawal or infection was found out in only ( %) patients. main causes of hypothyroidism were thyroiditis and thyroidectomy. thirtytwo ( %) patients had alteration of consciousness with a median glasgow score at ( - ). in addition, median heart rate at icu admission was ( - ) bpm while hypothermia < °c was noted in ( %) patients. median tsh level at admission was ( - ) mui l, t and t levels respectively ( - . ) pmol l and ( - . ) pmol l. rhabdomyolysis was frequent with median cpk level ( - ) ui l. organ support including mechanical ventilation, catecholamine infusion and, renal replacement therapy were respectively used in , , and % patients. lastly, % patients received oral levothyroxine whereas the intravenous form was used in others. overall icumortality was %. our preliminary data showed that severe manifestations of hypothyroidism leading to icu admission represent de novo hypothyroidism in two-thirds of patients, leading to a high mortality. introduction: when it comes to infections of the central nervous system (cns), the greatest challenge in the emergency department (ed) is to identify patients that have a rare life-threatening diagnosis. alone or in combination, fever, headache, altered mental status encompass a broad differential diagnosis. antibiotics or antiviral therapy should be given as soon as possible, ideally after both blood and cerebrospinal fluid (csf) have been obtained. early treatment is associated with a lower mortality. patients and methods: we present here, a four-year ( - ) retrospective and monocentric study. during the period of the study, we included all adult patients with the diagnosis of cns infection (positive csf culture). we collected and analyzed all clinical, biological, imaging, treatments and evolution datas during the stay. a total of patients with cns infection have been included for statistical analysis. we analyzed a second group (n = ) with suspected cns infection (negative csf) as a control group. results: in the study population, mean age was ± . years old and the sex-ratio was . . there were no difference between the two groups in terms of clinical signs except for more altered mental status in the control group (p = . ). all patients of the study (n = ) benefited of lumbar puncture (lp) in the ed with an average time of ± min after admission. this delay was the same between the two groups (p = . ) but was significantly higher in the encephalitis subgroup (n = , p = . ). patients who had imaging (ct or mri) during the ed stay had more likely a delay in lp realization ( vs min, p = . ). patients where the cns infection diagnosis was firstly evoke by the triage nurse had lp more quickly (p = . ). the median door to-antibiotic-time was min with no difference between the two groups of the study (p = . ). % of all patients were hospitalized for an average length of stay of . ± . days and % of them were admitted in the icu. the inhospital mortality was % in the study population. introduction: there are numerous causes of acute exacerbations of copd (aecopd), the most common of which are bronchial and or pulmonary infections. viral etiologies may account for % of aecopd, but this rate is likely underestimated because of the limited performance of the conventional diagnostic tests. multiplex molecular diagnostic tests may identify several pathogens including viruses and bacteria, from a single respiratory tract sample, with high sensitivity. using these tests, respiratory viruses are identified in to % of cases, according to the series. the objective of this work was to describe the microbial epidemiology, the management and the outcome of patients admitted to the intensive care unit (icu) with moderate to severe aecopd, in the era of multiplex testing. a prospective non interventional multicenter study conducted in two university-teaching hospitals. in addition to the usual samplings, a nasopharyngeal swab was performed for multiplex polymerase chain reaction (pcr), using respiratory panels fil-marray biomérieux ( viruses and bacteria) or eplex automaton ( viruses and bacteria) depending on the center. the preliminary results involve the patients ( males + years ( - )) included in tenon hospital over a -month period. the mean fev was % ( - ) median % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . drug therapies included anticholinergics (n = + %) and beta- -mimetics (n = + %), inhaled (n = + %) or oral (n = + %) steroids, and azithromycin (n = + %). a respiratory virus was identified in patients ( %), alone or in combination with a bacterium (n = ). a bacterial pathogen was identified alone times ( %). therapeutic interventions did not differ depending on whether a virus was detected or not-exposure to antibiotics ( ± . vs. . ± d + p = . ), administration of oseltamivir ( / vs. / + p = . ), steroids ( / vs. / + p = . ) and mechanical ventilation ( / vs. / + p = . ). the icu length of stay ( . ± . vs. . ± . d + p = . ) was similar. the icu and d-mortality rates were . and . %, respectively. conclusion: respiratory viruses are frequently involved in moderate to severe aecopd. the respiratory multiplex pcr should be performed in this setting and the results should be taken into account to more adequately use the anti-microbial treatments. introduction: prophylactic non-invasive ventilation (niv) is a well established method for prevention of post-extubation acute respiratory failure in hypercapnic patients. however, its role in the postextubation period, in traumatic brain injury patients, is uncertain. especially, because of effects of the brain injury, on respiration and airway control. we perform a study to assess the impact of prophylactic niv after extubation among patients with severe traumatic brain injury. patients and methods: over a period of year, adult patients with isolated severe traumatic brain injury, who were under invasive mechanical ventilation for more than h were eligible for inclusion in the study. they were randomized, after decision of extubation, to receive conventional therapy or conventional therapy associated with niv. conventional therapy consisted of oxygen delivery by facial mask, semi-recumbent position, mucus suctioning and nebulization therapy. the main objective of the study is to assess the impact on reintubation rate. extubation succes was defined by the absence of need for reintubation within the days. the secondary objective is to evaluate the effect on icu length of stay after extubation. the clinical benefit of non-invasive ventilation (niv) in patients with acute hypoxemic respiratory failure (arf) is being called into question. indeed, in a multicenter randomized trial recently conducted in hypoxemic arf patients (pa fi < ), intubation rate in the niv group was % and intensive care unit (icu) mortality rate was %, numbers higher than in the standard-oxygen group ( ) . an excessive tidal volume under niv is a hypothesis to explain these bad outcomes ( ) . our experience does not seem to support these data. therefore we wanted to-investigate the rate of niv success in hypoxemic arf and global in-icu mortality. estimate the average expired tidal volume and identify predictive factors of niv failure. conclusion: though limited by its design, our study seems to show a similar efficacy of niv following ue as compared to planned extubation, with a safety concern for rescue niv and a potential interest for "prophylactic" niv. further data is warranted. which is yet operator dependent and time-consuming, or by invasive methods including esophageal pressure or diaphragmatic electromyogram measurements. the main purpose of this study was to assess the relevance of curvex as a noninvasive diagnostic and classification tool for asynchronism management. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct ) that aims to record consecutive icu patients, over -years. all consecutive patients were recorded for a -hours period during -h following icu admission. all measurements were recorded with the patient laying supine, with a ° bed angulation. raw ventilatory pressure and flow curves were transferred to a centralized server using a dedicated network. the physician in charge of the study was informed of the online analysis on a routine basis. physiological recordings were associated with metadata collection. asynchronisms detection is based on a non-parametric hypothesis testing (random distortion testing), that requires no prior information on the signal distribution. beside asynchrony index monitoring (ai), five asynchronism's types were qualified-ineffective efforts (ie), short cycles (sc), multiple cycles (mc), prolonged inspiration (pi) and premature cycling (pc introduction: international guidelines recommend ultrasound (us) guidance for central venous catheter (cvc) insertion. however, evidence is lacking for several aspects of guidance such as probe shape or whether the needle has to be in plane (ip) or out-of-plane (oop). we assessed these issues in a randomized trial. success at first pass, number of attempts (needle passes), success, times between skin contact and needle skin penetration and between needle skin penetration and liquid back flow in the syringe were recorded. qualitative and quantitative values are expressed as number (percentage), and median (range), and were compared using the wilcoxon matched pairs test and the fisher exact test, respectively. results: for ijv puncture, first attempt success rate was more than % and was neither influenced by probe shape nor approach (table ) . conversely for rav puncture, using lp with ip approach was more frequently successful at first attempt ( vs %, p = . ). time elapsed between needle skin penetration and liquid back flow was shorter for rav puncture using ip approach ( s vs s, p = . ). time elapsed between probe appliance on skin and liquid back flow was significantly shorter with the linear probe for ijv whatever the approach and for rav using ip approach. rav puncture was more frequently impossible with mcp ( vs %, p = . ). arterial puncture occurred more frequently with mcp ( vs %, p = . ). lp use and ip approach were associated with more free event puncture ( ± ) . minimal ani, reflecting intense stress was . (± . ). objective and subjective stress of each team leader is shown in fig. . there was a significant negative linear correlation between minimal ani and maximal hr (rho = − . , p = . ). there was no significant correlation between self-reported stress vas (neither pre hfs or maximal stress) and minimal ani. conclusion: hrv monitoring is a feasible method to evaluate continuous physiological stress for team leaders in highly stressful simulationteaching. upgrading signal connection by bluetooth . or wi-fi could improve the method. focusing on specific stressful time points might improve stress assessment and its correlation with performance. introduction: simulation training has become available in health sciences faculties and proposed in many specialties. intensive care is one of the fields of development of simulation based training. the aim of the present study was to report the experience of the faculty of medicine of monastir simulation center in training medical students and residents in intensive care and to compare their respective perceptions. this was a descriptive study including students ( th year of the medical curriculum) and residents who received training during the last academic year ( ) ( ) , in the simulation center during their icu traineeship. simulation training was based on high-fidelity mannequins for students and seminars with high fidelity and procedural simulation training for residents. three sessions per group were organized for students and a total of five sessions for residents. we collected participant characteristics and used likert scale (from to ) to assess participant satisfaction, simulation fidelity, impact on clinical practice, stress level and instructor behaviors. chi test was used to compare students' and residents' perception of the simulation based-training. results: during the study period students (of the students' whole promotion) and residents actively participated at least in one of the simulation-based training sessions. median students' and residents' ages were respectively years ( - ) and years ( introduction: hospitals are encouraged to edit local antibiotic therapy guidelines. antibiogarde ® is an electronic antibiotic prescription referential developed by a multidisciplinary team of french physicians, regularly updated, and locally customizable, which has been purchased by more than french hospitals. we compared adequacy fig. team leader's objective (heart rate and ani) and subjective stress (declared vas stress) of initial antibiotic prescription by icu clinicians, antibiogarde ® proposal and national or international guidelines. patients and methods: between january and june , initial antibiotic prescriptions in an icu were retrospectively analyzed when microbiologically documented. antibiogarde ® and guidelines proposals were simulated, considering data available at the time of initial prescription. adequacy was defined when all bacteria responsible for infection were sensitive to at least one prescribed proposed antibiotic. national guidelines were used when published after . otherwise, most recent international guidelines were used. results: initial prescriptions were analyzed ( monotherapy) in patients (median age y, median saps ii , median sofa on prescription , icu mortality %, % immunocompromised). main sources of infection were lung (n = ) and intra-abdominal (n = ). leading isolated bacteria were enterobacteriaceae (n = , antibiotic resistance in ), streptococci (n = ), non-fermenting gram negative bacilli (n = , antibiotic resistance in ) and staphylococci (n = , resistance to methicillin in ). in the clinical settings analyzed, there was a proposal by antiogarde ® in ( %) and a guideline available in ( %) (p = . introduction: intubation is plagued with a high morbimortality, especially in emergency situations. it is now acknowledged that a seated position allows for optimized preoxygenation ( ) . however, there is no guideline concerning the patient's position for intubation. the patient is most often laid in a supine position, leading to a higher risk of aspiration ( ) . face-to-face intubation in sitting position (ftfi) would allow for an easier intubation and a lower morbidity. we focused on learning the ftfi technique using the macintosh laryngoscope and the airtraq videolaryngoscope in simulated difficult intubation situation and comparing the performance of the ftfi with the classic technique. the participants would intubate a high-fidelity manikin (simman g, leardal, norway) configured with a tongue edema (cormack b- ). for each trial, time to intubate (tti), success and complication rate, intubation difficulty and glottis exposure were noted. in classic position, three trials were performed with the airtraq followed by the laryngoscope in order to obtain baseline parameters. in ftfi, at least intubations were performed by each participant for each device. the utilization order was randomized. results: thirty physicians, with an experience of at least intubations each, were included. figure shows the learning curves of the ftfi based on the evolution of the tti measured for the airtraq and the laryngoscope. in classic position, the mean tti with the airtraq was . ± . s versus . ± . s with the laryngoscope (p = ns). in ftfi, once the technique mastered, the tti was ± . s with the airtraq versus . ± . s with the laryngoscope (p < . ). success rate, tti, complication rate, intubation difficulty and glottis exposure were better using ftfi versus classic intubation (p < . ). these parameters were even better with the airtraq than with the laryngoscope (p < . ). the learning profile of ftfi is different between the airtraq and the laryngoscope. it could be due to the participants' lesser familiarity with the airtraq. the better performances in ftfi could be due to better ergonomics allowing easier glottis exposure and learning ( ) . conclusion: face-to-face intubation in sitting position is easy to learn. it provides better performances and fewer complications than the classic intubation technique which might result in a lower morbidity. the airtraq provides even better results than macintosh laryngoscope. all participants recommend their colleagues to be trained in face-toface intubation. among non-invasive respiratory support, niv with bilevel pressure was the most frequent (n = , %) before cpap (n = , %) and high flow oxygen (n = , %). the proportion of patients on niv was up to % in the centres hosting more acs patients. conclusion: despite the absence of evidence from randomized controlled trials niv is nowadays commonly used in picu and hdu for scd patients with acs, especially in centres taking in charge a high number of scd patients. future physiological studies and randomized controlled trials might help to choose between the different ventilatory support options for acs. in transfused patients, the pre-transfusion hemoglobin was . ( . - . ) g dl in moderate pards and . ( . - . ) g dl in severe pards. the evolution of hemoglobin, osi, scvo and lactate after the transfusion is reported in the table . in our picu, a relatively restrictive policy of rbc transfusion was observed even in patients with severe pards. decision to transfuse seemed associated with the general severity status of the patient and with the hemoglobin level. further studies are needed to explore the generalizability of these findings, and to investigate the impact of transfusion on oxygen transport consumption balance in pediatric acute respiratory distress. introduction: pharmacokinetic parameters are altered in critically ill patients. for instance, in adult patients, it has been well demonstrated that augmented renal clearance results in subtherapeutic antibiotic concentrations. our objectives were to build a pediatric population pharmacokinetic model for piperacillin, in order to optimize individual dosing regimen. patients and methods: all children admitted in pediatric intensive care unit, aged less than years, weighing more than . kg, and receiving intermittent piperacillin infusions were included. piperacillin was quantified by high performance liquid chromatography. pharmacokinetics were described using the non-linear mixed effect modelling software monolix. monte carlo simulations were used to optimize dosing regimen, in order to maintain plasma concentration above the minimum inhibitory concentration ( mg l − for pseudomonas aeruginosa) throughout the dosing interval ( % ft > mic). results: we included children with a median (range) post natal age of . ( . - . ) months, median (range) body weight of . ( . - ) kg, median (range) pelod- score of ( - ) and median (range) estimated creatinine clearance of ( - ) ml.min - .m - . a one compartment model with first-order elimination adequately described the data. median (range) values for piperacillin clearance and volume of distribution were respectively ( . - ) l h − and . ( . - . ) l. body weight (allometric relationship), estimated creatinine clearance and pelod- severity score were the covariates explaining the estimated between subject variability. a third of the cohort attained the target, according to our dosing regimen and to the european guidelines. to reach the target and according to the simulated dosing regimens, children with acute kidney injury should receive intermittent infusion every h, administered on min. those with augmented renal clearance should receive a continuous infusion. to reach the target, standard intermittent piperacillin dosing regimen in critically ill children is not appropriate. in addition to body weight, dosing regimens should take into account the creatinine clearance. continuous infusion is adequate for children with augmented renal clearance. piperacillin individualized dosing regimens and therapeutic drug monitoring are mandatory in pediatric intensive care unit. introduction: all data support the need for early recognition, evaluation of pain in the nicu. multiparametric analysis including physiological parameters could be useful to have a more objective evaluation of pain in the nicu compared to scales built on external-evaluation. the newborn infant parasympathetic evaluation (nipe ® ) was developed to assess pain in newborns and infant, from preterm to the age of years. patients and methods: we conducted a monocentric, prospective study to compare the instantaneous nipe ® index value (nipei ® ) to the dan scale during acute procedural pain (picc line insertion) in preterm infants (under gw). the operators and the nurse were blinded to the continuous recording of nipei ® during the entire procedure. dan scale was assessed every min by a third person, trained to this scale and blinded to nipei ® . a direct correlation assessment between the dan scale and the nipei ® was performed by calculating the pearson's linear correlation coefficient. the differences between the nipei ® of non-painful (dan < ) and painful (dan ≥ ) infants were estimated by the wilcoxon-mann-whitney test. the usefulness of nipei ® as a new tool for pain assessment in neonates was estimated by the corresponding roc curve. our study was approved by our local ethic institutional review board. results: thirty-five preterm infants were included, nipei ® data were incomplete in infants. fifty percent of newborns were born before gw, and % had non-invasive respiratory support (continuous positive airway pressure cpap). at the time of the procedure, newborns had a median post-natal age of days and a median weight of grams. there was a moderate correlation between the nipei ® index and the dan scores (r = . + p < . ). the median nipei ® index was for non-painful events vs. for painful events, p < . . the area under the roc curve was . . for a threshold of nipei ® < , the sensitivity was . %, the specificity was %. positive likelihood ratio was . and the negative likelihood ratio was . ( fig. ) . we showed a correlation between the dan scale and the nipei ® index for pain assessment in preterm infants. the nipe ® monitor could be a useful and non-invasive tool for pain assessment in neonates. further studies are needed to confirm our results and to define more precisely the place of such monitors for pain evaluation in daily clinical practice in the nicu. introduction: the aim was to identify factors associated with the occurrence of acute pituitary hormone dysfunction in children with moderate to severe tbi and to describe the impact of this dysfunction on the stability of the children. patients and methods: prospective bicenter study including all children aged between month to years, admitted to picu for a moderate-severe tbi and with an expected stay > days. setting-pediatric intensive care units of grenoble and lyon, from to . endocrine explorations at the second morning following admission and h before discharge were performed-cortisol h cycle with free cortisol and acth dosages every h (or h if no central line) + free h urinary cortisol + tsh and t l, h urinary lh and fsh, blood level of testosterone or estradiol for children aged > years, and igf . patients were classified as having cortisol insufficiency if all the cortisol dosages were < nmol l and all acth were < pg l. tsh deficiency was defined as t l < . pmol l and tsh < . mui l. gonadotropin defciency was defined as urinary lh < . ui h and urinary fsh < . ui h for males + urinary lh < . ui h and urinary fsh < . ui h in female. patients with deficiency (acth and any deficiency) were compared to those without deficiency in terms of hemodynamic instability, respiratory instability, neurological and infectious complications for continuous variables means and % confidence interval were calculated and compared by t student test. chi- test was used to compare proportions. results: among the patients evaluated, had acth deficiency, and had at least one acute pituitary dysfunction. comparison of patients who presented acth deficiency with those who were not deficient found no differences in terms of patients characteristics, cause of tbi, level of severity and level of injury. paitents with acth deficiency required more frequently fluid bolus at day ( vs %, p = . ). all the markers of severity were higher and the need of vasoactive drugs were more frequent but the differences were not statistically significant. table shows comparison between patients with at least one pituitary hormone deficiency to those without deficiency. the same result was found. glycemia levels were lower in the group with deficiency. conclusion: we didn't find any predictive factors of pituitary hormone deficiency in children with moderate-severe tbi justifying a systematic screening of those patients. introduction: most intensive care unit (icu) patients cannot make decisions themselves. familiy members are actively involved in the care process as surrogate decision-makers and judges of care quality. however, family satisfaction with care is complex and is not clearly defined. the aim of this study is to evaluate the different procedures (reception book and staff education for aid and relationship) used in a new icu to improve the family care. patients and methods: we included in our study patients who had spent more than h in our department. a questionnairy, adapted to our population, was performed by our staff and validated by the hygiene and quality care departement. we proceded by phone calls, months after the inauguration of our icu. results: sixty-five questionnaires were included (fig. ). the average of age was ± with a sex ratio of . the average of the simplified acute physiology score (sapsii) was ± . the median stay was days [ - ] with a total mortality rate of %. mostly, we interrogated first-degree parents (n = ). only three families recieved reception book at admission. visit in patient room was autorised only for % (n = ) of family members. only four persons said they were disturbed in visit hours for architectural reasons (tight space). disponibility was found excellent in % (n = ) of cases for medical staff, % (n = ) for paramedicals. informations provided by physicians were clear in . % (n = ) of cases. fifteen of the family members ( %) asked psychology support. patients were followed up via phone calls during year after discharge. characteristics on admission and outcomes after discharge were analyzed stratified by ventilation modality niv vs imv. the overall survival was analyzed on the basis of the kaplan-meier curves. results: during the predetermined period of data collection, the follow-up involved patients. patients were treated by niv (group ) and patients needed imv (group ). there was no difference between the groups in age (p = . ), severity of copd (p = . ), physiological reserve at discharge (p = . ) and icu readmission (p = ). short term outcomes were not different between the groups- -month readmission ( . vs % respectively in niv and imv, p = . ) and -month mortality ( introduction: post-intensive care syndrome (pics) has been recently described as a combination of physical, cognitive and mental impairments appearing during a stay in an intensive care unit (icu). the prevention and detection of pics require the participation of each category of healthcare workers. however, the level of knowledge is unknown. we sought to assess the awareness among our icu staff in preparation for a follow-up consultation. the study used a short multiple-choice survey filled on a voluntary basis. all members of the staff were asked to fill the questionnaire over a one-week period. the assessment was composed by seven structured questions which aimed measure basic knowledge of post-intensive care syndrome and general strategies to diagnose that syndrome and the tests used. results: fifth five workers ( % of the staff ) of the department of intensive care answered the questionnaires ( % nurses, % physiotherapists, % physicians). the estimated ranges of prevalence of psychological problems were very low ( - %) for . %, low ( introduction: drafting a death certificate (dc) is a procedure considered as a part of doctor's daily practice, especially in emergency and intensive care departments. this certificate represents a civil, social, epidemiological and medico-legal act. it can engage the liability of the certifying doctor. the objectives of our study were to examine the content of dc drafted in emergency and intensive care departments, assess the quality of writing, and analyze drafting errors. patients and methods: a prospective study extended over a period of months from january to december , including all dc emanating from emergency and intensive care departments and received in the forensic department of habib bourguiba hospital in sfax. results: during the study period, dc meeting the inclusion criteria were collected. although confidential, the medical part of the dc was sealed by the doctor in onlyone third of cases. in the administrative section, nine socio-demographic parameters were studied. in % of the cases, less than four of the nine criteria were found. in the section concerning the certifying doctor data, parameters were screened. . % of the certifying doctors met at least six criteria. the most frequently missing parameter in this section was the identity of the person to whom the certificate was issued. the identity of the doctor was not mentioned in % of the cases. forensic data ( items) was complete in over three quarters of the certificates. nevertheless, in . % of cases, the medicolegal obstacle to burial box was left empty ( . %) or not ticked even if judicial investigation was required ( . %). the section on causes of death was the source of almost all of the drafting errors. we have classified these errors into six major ones, according the classifications reported in the literature. the percentage of certificate without faults was %. the most common major error was insufficient cause of death found in . % of cases followed by incorrect sequence of causes of death ( . %), medicolegal obstacle to burial not ticked although required ( . %), several causes of death mentioned simultaneously ( . %), unacceptable cause of death ( . %) and mechanism of death mentioned instead of the cause of death ( . %). our study showed that the quality of drafting of dc suffered from several insufficiencies, which encourages us to provide more effort in training doctors and to review the current official model of dc. introduction: septic shock is defined as a sepsis with hyperlactaemia greater than mm after correction of hypovolemia requiring vasopressors to maintain mbp > mmhg [ ] . it can be observed in pre-hospital emergency medicine (phem). the use of a reliable portable device for measuring lactate in phem would allow a better evaluation of septic patient facilitating their orientation towards intensive care unit (icu) or emergency department (ed). this portable delocalized biology device must be validated against the laboratory reference method (nfen iso ) [ ] . the aim of this study was to clarify the validity of a delocalized measure of lactatemia. we performed a prospective study including patients admitted into icu for septic shock (cpp number - - sc). lactate was measured in parallel on samples-one capillary with the portable device (lactate statstrip xpress, nova biomedical) and the other venous on a centrifuge tube for plasma analysis (architect c abbott diagnostics). we evaluated the analytical performance (coefficients of variation (cv) for repeatability and reproducibility evaluated at levels of quality control (qc)- . and . mm) and then the concordance between lactate levels measured by the devices and lactate levels measured by laboratory analyzer. results: at the qc concentrations tested, the cvs were in agreement with the limits set by the french society of clinical biology-cv < % for repeatability and < % for reproducibility. an excellent correlation was observed between the measurements-correlation coefficient r = . , slope = . and ordered at the origin = . . the latter suggested a low positive bias of the device not confirmed by bland-altmann graph analysis and graph of the differences. we verified the analytical performance of the device and showed an excellent correlation with the laboratory measurement. the delocalized measure can be used in phem in patients with suspected sepsis syndrome. this measure should allow a more accurate and early assessment of their severity in order to improve triage and hospital orientation between ed and icu. there is an association between mortality at d and hyperoxia in patients admitted in icu for refractory ohca requiring ecpr. these data underline the potential toxicity of high dose of oxygen and suggest that control of oxygen administration in such patients is an important part of the treatment. a value of pao between and mmhg after starting ecpr seems to be a target during treatment of ohca treated by ecpr. introduction: sepsis has been defined as a dysregulated host response to infection leading to life-threatening organ dysfunction (singer m et al., jama ) . a qsofa score relying on simple clinical criteria (respiratory rate, mental status and systolic blood pressure) has been proposed to better identify septic patients with associated higher mortality outside the intensive care unit (seymour cw et al., jama ) . the study aim was to evaluate the ability of qsofa to predict the development of organ failure and increased -day mortality in patients admitted for suspected sepsis in the emergency department (ed). patients and methods: prospective study conducted over a period of months comparing the prevalence of organ failure and -day mortality according to the value of qsofa at admission to the ed between group a (qsofa > = ) and group b (qsofa < ). as part of routine care, an electronic sepsis form was specifically created to identify prospectively and exhaustively all eligible patients on-line. for the purpose of the study, sepsis diagnosis was independently validated off-line by an adjudication committee which included three physicians who reviewed clinical, biological and microbiological data. for each patient, demographic data, source of infection, qsofa and sofa score, biological data and -day mortality were recorded. seventy-six patients of group a ( %) were hospitalized, of whom were admitted to the intensive care unit ( . %), and -day mortality reached . %. in group b, only patients developed an organ failure ( . %) and -day mortality was . % (table ) . the present study confirmed that the qsofa score is a reliable and practical tool to predict the development of organ failure and higher -day mortality in patients with suspected sepsis in the ed. limits of ct scan criteria and intravascular contrast extravasation to define pelvic angioembolization need: a specific assessment on the risk of false- introduction: opening of the mitochondrial permeability transition pore (ptp), triggered by cyclophilin-d (cypd) binding under stress conditions, plays a key role in ischemia-reperfusion injury. we sought to determine, using transgenic mice, whether cypd deletion (cypd −) would improve resuscitability and survival after experimental cardiac arrest (ca). additionally, we compared the protective effects of cypd deficiency with that of targeted temperature management (ttm). patients and methods: anesthetized mice underwent a min asphyxial ca followed by resuscitation (cardiac massage, resumption of ventilation, epinephrine). four groups of animals were studied-sham, control (ctrl), cypd-ca using mice lacking cypd (knockout mice), and ttm-ca with fast hypothermia induced by external cooling at reperfusion ( °c for h). two hours after ca, the following measurements were carried out (n = - group)-echocardiography, cellular damage markers (including s b protein and troponin ic) and mptp opening in mitochondria isolated from brain and heart. additional mice (n = - group) were included in the same groups for survival follow-up ( h and days). results: characteristics of ca were similar among groups. rate of restoration of spontaneous circulation (rosc) was significantly higher in cypd-and ttm groups compared to controls (p < . ). time to rosc was shorter in cypd-versus ttm and ctrl (p < . ). genetic loss of cypd and ttm prevented to a similar extent ca-induced myocardial dysfunction, increase in blood levels of both s b protein and troponin ic (p < . versus ctrl). ca resulted in a significant increase in ptp opening only in mitochondria isolated from brain (p < . versus sham). cypd deletion as well as ttm limited ca-induced ptp opening in brain (p < . versus ctrl). short-term survival ( h) was significantly improved in the cypd-and ttm groups when compared to controls (p < . ). however, only therapeutic hypothermia improved survival at day (p < . versus ctrl). in our murine ca model, genetic loss of cypd increased resuscitability and short-term survival but, unlike therapeutic hypothermia, failed to improve -day survival. introduction: early prediction of neurological outcome of post-anoxic comatose patients after cardiac arrest (ca) is challenging. prognosis of comatose patient relies on multimodal testing-clinical examination, electrophysiological testing and structural neuroimaging (mainly diffusion mri). this prognostication is accurate for predicting poor outcome (i.e. death) but not sensitive for identifying patients with good outcome (i.e. consciousness recovery). resting state functional mri (rs-fmri) is a powerful tool for mapping functional connectivity, especially in patients with low collaboration. several studies showed that rs-fmri can differentiate states of consciousness in chronically brain-damaged patients. a recent study also showed that functional neuroimaging can early detect signs of consciousness in patient with acute traumatic brain injury. however, rs-fmri has not been assessed for the early prognostication of post-anoxic comatose patient. we assessed whole-brain function connectivity (fc) of post-anoxic comatose patients early after ca using rs-fmri. nine patients ultimately recovered consciousness (good outcome) while eight died (poor outcome). we estimated fc for each patient following a procedure previously described. we statistically compared whole-brain fc between good and poor outcome group, to assess which brain connections differed between them. then, we trained a machine-learning classifier (a support vector machine, svm) to automatically predict coma outcome (good poor) based on wholebrain fc of comatose patients. finally, we compared this outcome prognostication based on functional mri to those using standard structural diffusion mri. results: good and poor coma outcome groups were similar in terms of demographics, except for time to rosc. good outcome group showed significant increase in whole-brain fc between most cortical brain regions + with the strongest changes occurring within and between occipital and parietal, temporal and frontal regions ( fig. ). using whole-brain fc and a svm classifier to predict coma outcome yielded to an overall prediction accuracy of . %(auc . ). interestingly, automatic outcome prognostication using functional neuroimaging achieved better results that structural neuroimaging methods like dwi (accuracy . %). conclusion: we used rs-fmri to predict coma outcome in a cohort of post-anoxic comatose patients early after ca. we deliberately chose to include only patients with indeterminate prognosis after standard multimodal testing, to assess the contribution of rs-fmri in the early prognostication of coma outcome. we found that automatic prediction based on functional neuroimaging yielded much better results than current dwi methods, notably for identifying patients who recovered consciousness. outcomes of post-anoxic comatose patients early after ca, using rs-fmri in rcts comparing treatment of severe pneumonia that may influence their ability to demonstrate differences between studied drugs. clinical cure was the most frequently used endpoint but its definition was highly variable. these results are not surprising as far as even guidance from regulatory agencies on how to evaluate hap vap treatments differ. the aim of this work was to reach a consensus on the most appropriate endpoint to consider in future clinical trials evaluating the efficacy of antimicrobial treatment for hap vap, using delphi method. patients and methods: twenty-six international experts from intensive care, infectious disease and from the industry were consulted using delphi method (four successive questionnaires) from january to january . more than % of similar answers to a question were necessary to reach a consensus. results: according to % the experts, clinical cure was the most desirable primary outcome among those found in the literature but two other endpoints were highly rated-all-cause mortality and mechanical ventilation (mv)-free days. consequently, % of the panelists agreed to use a composite endpoints and even a hierarchical composite endpoint to combine these items together in which clinical cure and mv-free days would be assessed at day and clinical cure at day after end of therapy. for vap, mortality was considered as the most clinically significant item by % of the experts, followed by mvfree days and finally clinical cure (fig. ) . for hap, a dual composite endpoint that only included all-cause mortality and clinical cure was chosen ( fig. ). among the various elements of clinical cure definition found in the literature, only three were retained by the experts-resolution at end of therapy of signs and symptoms present at enrolment, no further antimicrobial treatment needed and resolution or lack of progression of radiological signs of pneumonia. finally, we found a consensus on the signs and symptoms that should trigger the suspicion of pneumonia-worsening of gaz exchange, purulent tracheal secretions, hypotension and or vasopressor requirements and fever or hypothermia. we provide here two consensual endpoints (for vap and hap) that would help addressing the efficacy of antimicrobial molecules for hap vap treatment in future clinical trials. (table) . sm-vap were matched with control patients. in univariate analysis, risk factors for sm-vap weremale gender, chronic heart failure, respiratory, cardiovascular and coagulation sofa scores two days before vap, median number of antibiotics used, percentage of time with antibiotics before vap, parenteral nutrition, dialysis, catecholamine use and exposure to ureido-carboxypenicillin, ciprofloxacin, tazobactam or imipenem-meropenem during the week before vap (table) . patients with sm-vap were less likely to receive initial adequate therapy ( vs %, or . , p = . ). there was no statistical difference for icu or d mortality. d mortality was higher for sm-vap (table) . in multivariate analysis, exposure to imipenem-meropenem during the week before vap, respiratory and coagulation sofa scores two days before vap were independent risk factors for sm-vap. sapsii: simplified acute physiology score; sofa: sofa (sequential organ failure assessment); sofa resp: sofa respiratory score; sofa coag: sofa coagulation score; sofa cardio: sofa cardiovascular score conclusion: sm-vap represented . % of vap. we observed no differences in patients characteristics between the groups. imipenem-meropenem use during the week before vap was the most important risk factor for sm-vap. the higher risk of inadequate initial therapy with sm-vap had no impact on d mortality but d mortality was significantly higher. introduction: education of undergraduate students is key to improve hand hygiene (hh) behavioral changes amongst doctors [ . ] . our aim was to evaluate personal feedback using ultraviolet (uv) light inspection cabinets in a years program. our hypothesis was that its use for alcohol hand rub (ahr) application on first year would increase complete ahr application on nd year. patients and methods: this was a simple blind randomized trial comparing hh training with personal feedback using uv cabinet to a control group. on first year, students had access to a theoretical formation then were convened by groups for a demonstration of the correct execution of world health organization's (who) procedure [ ] . before hh training, each group underwent a cluster randomization. in the control group, the student hand rubbed under visual supervision and advises of a trainer. in the intervention group after the same visual assessment, completeness of ahr hand application was recorded under uv light and shown to the student. he was given free access to the uv cabinet to repeat the technique, until perfect application complete under uv light. an enhancement with a scenario-based learning was proposed to both groups. on second year, every student were asked to hand rub with the fluorescent ahr. a supervisor blinded to the group of randomization assessed the quality of the hh procedure visually, the completeness of hand application under uv light and compliance with the who's opportunities for hh during the simulation. results: after randomization students were included in the intervention group and in the control group. on second year, the rate of complete application of the ahr under uv was increased in the intervention group as compared with the control group ( % versus . % p < . ) ( fig. ) despite that visual assessment of hh procedures was similar between the two groups. in a logistic regression model including gender, intercurrent hh formation, intercurrent uv cabinet use, surgical unit traineeship and report of regular use of ahr, the hazard ratio for the intervention was . (ic . - . ). the rate of perfect compliance with the hh opportunities in the intervention group was increased ( . % versus . % p < . ) and the effect persisted in the logistic regression. conclusion: uv cabinets for undergraduate students' hh education improve the technique and the compliance with hh opportunities. included in a multifaceted education program, it must be considered a key tool for training. results: among the patients who underwent ecmo support for more than h, the bsi prevalence was . cases per ecmo days and microorganisms associated were most frequently gramnegative bacilli. as for positive ta cultures, microorganisms associated were oropharyngeal germs and gram-negative bacilli. two risk factors were associated with nosocomial bacteria occurrence in ta cultures-prior antibiotics and duration of mechanical ventilation more than days. we demonstrated a link between "positive ta culture" and "positive blood culture" and we showed a protective effect of using an antibioprophylaxis on "positive ta culture" and "global positive cultures" development. introduction: delirium in the icu is often under-diagnosed despite its related burden and impact on patients' morbidity, mortality and prolongation of hospital length of stay. the aim of this study was to assess the medical and paramedical community beliefs and practices regarding delirium in tunisian icus. patients and methods: between august st and / , healthcare professionals working at the icus of university hospitals of monastir and mahdia (tunisia) were asked to participate in the survey by completing a questionnaire anonymously (that specified participants' characteristics (age, gender, function, years of experience in icu) and their knowledge and perception of delirium in icu. the questionnaire consisted in questions of different types: likert style (: widespread scale in psychometric questionnaires in which the respondent expresses his or her degree of agreement or disagreement with an assertion), multiple choice, ranking and yes/no). results: during the study period, respondents out of ( % female, nurses: %), aged between - years in %, responded to the questionnaire. healthcare professionals experience in the icu was < year in . %; - years in . %, and > years in . %. participants asserted that the "most characteristic signs of delirium" were: insomnia ( %); confusion ( %); agitation ( %) and aggressiveness ( %). three-quarters of participants said they did not systematically search for signs of delirium in their patients. % thought that delirium was "an insignificant problem" or that "it was not a problem". only one and three participants respectively, said they attended a conference and read an article about delirium in icu the last year. half of the respondents felt that the most appropriate treatment for a patient with delirium was restraint. nearly one-third of participants thought that delirium was an under-diagnosed entity and only % felt that it was associated with long-term neuropsychological deficits. factors considered to be determinant in the occurrence of delirium were ards, shock, age, mechanical ventilation, postoperative status in , , , and %, respectively. conclusion: most tunisian healthcare professionals consider delirium as a common, underdiagnosed, and serious problem in the icu. yet, few participants actually monitor this condition. the influence of sedation choice on the delirium occurrence in critically ill poisoned patients: a randomized controlled trial khzouri takoua introduction: delirium is a common manifestation of acute brain dysfunction in critically ill patients. it is associated with a healthcare cost increase, and extension of the hospital stay length. the present study aimed to explore influence of patient characteristics and analgesicsedation on delirium incidence and to analyze its risk factors. patients and methods: it is a prospective single blind randomized controlled trial, started on the first july in a -bed toxicological intensive care unit, including all mechanically ventilated patients requiring sedation who were admitted for acute poisoning. they were randomly divided into two groups g et g receiving respectevily propofol-remifentanil and midazolam-remifentanil. delirium assessment scores were judged not adapted to our population and we retained the diagnosis of delirium on arguments inspired from diagnostic and statistical manual of mental disorders fourth edition (dsm-iv). results: until the th september , patients were included, with patients in g and in g . the two groups were comparable in terms of epidemiological characteristics. delirium was developed in patients ( %) (n = in g and n = in g ) with an average duration of ± h with no difference between the groups ( ± h for g - ± h for g , p = . ). compared to those without delirium, no differences were found in the patient characteristics among these two groups with regard to sex, age, psychiatric history and severity of illness (apache ii, igs ii score) and even with regard to hypnotic choice ( vs p = . ). delirium was associated to prolonged duration of mechanical ventilation ( ± h vs ± h, p = . ) and length of icu stay ( . h vs . h, p = . ) without significant differences. delirious patients had more hypotension (p = . ), and received more atropine ( . ). multiple logistic regression analysis identified atropine (or . , %cl . - . , p = . ) as an independent risk factor for delirium. the diagnosis and prevention of icu delirium are subjects of multiple ongoing investigations. we carried out this study to detect the risk factors of delirium in order to prevent it. it is important to note that our results are influenced by the studied population and are only preliminary. we rely on the study pursuit and the sample enlargement to better inform us as well on risk factors as protective. introduction: background: severe alcohol withdrawal syndrome is a common cause of hospital admission. delirium tremens is a potentially fatal complication of alcohol withdrawal. in severe delirium, very large dosages of benzodiazepines can be required despite well described side effects, such as coma and hypoxic cardiac arrest, although there is no recommendations for standardized treatments. objective -the aim of this study was to describe outcomes and risk factors for complications in patients with severe alcohol withdrawal syndrome treated in intensive care unit with continous infusion of benzodiazepine (bzd). we retrospectively reviewed the medical records of all patients hospitalized for alcohol withdrawal syndrome between and . only those who received continous-infusion of bzd, associated with close clinical monitoring and the evaluation of rass and cushman scores, without systematic recourse to mechanical ventilation, were included. results: we studied patients hospitalized in icu for severe alcohol withdrawal syndrome. the mean age (sd) was . ± . years, mean icu admission saps (simplified acute physiology score) ii score was ± . . all of them have received continous infusion of midazolam, with a median maximum perfusion velocity of mg h (interquartile range, ( , )). the median duration of treatement was days (interquartile range, ( , ) ). thirteen patients ( %) developed pneumonia, and or required intubation, and ( %) have had seizures. no cardiac arrest and death was observed. icu length of stay (los) was days ( , ) (median, interquartile range). patients who requiried intubation and or developed pneumonia, received substantially more bzd (median total dose, mg of midazolam vs. mg in the non-complicated group + p < . ), and their icu los was higher (median, days vs. days + p < . ). endotracheal intubation and or development of pneumonia were associated with a higher maximum perfusion velocity of midazolam (> mg h) (or . , ic % ( . - . ), p = . ). previous episodes of delirium tremens before icu admission were associated with higher complications such as mechanical ventilation and or pneumonia (or . , ic % ( . - . ), p = . ). in severe delirium, very large dosages of benzodiazepines can be used without systematic mechanical ventilation with a low incidence of complications. introduction: delirium is frequent in intensive care unit (icu) patients and is associated with increased mortality, increased hospital stay, increased cost and long term cognitive impairment in survivors. numerous pharmacological and non-pharmacological strategies have been investigated for delirium treatment without success. therefore delirium prevention strategies are recommended by current critical care practice guidelines. among the potentially modifiable risk factors for delirium, the impact of daylight exposure on delirium incidence and or duration has not been studied. the objective of this study was to investigate whether daylight exposition would reduce delirium burden in critically ill patients. we conducted a prospective study in a -bed medical intensive care unit (icu) over a -year period (january -january ). all consecutive adult patients receiving invasive mechanical ventilation (mv) for days or more were eligible for the study. patients were assigned to a room with windows allowing daylight exposure ("light" group) or without window ("dark" group), depending on bed availability. delirium was evaluated with the intensive care delirium screening checklist (icdsc) for a maximum period of days. delirium was defined by a icdsc score ≥ for two consecutive days. agitation was defined by a rass > or = + . the primary endpoint was cumulative incidence of delirium. data are presented as median (interquartile range) or number (percentage). results: a total of patients were included (age- [ + ] years, saps - [ + ], sofa score- [ + ], medical admission- %). of them, patients were admitted to a "light" group and to a "dark" group. incidence of known risk factors for delirium was similar in the two groups. delirium occurred in ( %) patients in the "light" group and in ( %) patients in the "dark" group (p = . ). the duration of delirium was [ + ] days. patients in the "light" group received significantly less neuroleptics to treat agitation than patients in the "dark" group ( vs. %, p = . ). this protective association persisted after adjustment for confounders in multivariate analysis (odds ratio = . + [ . + . ] + p = . ). daylight exposure does not impact on delirium burden in icu mechanically ventilated patients. however, daylight exposure is independently associated with a reduced prescription of neuroleptics to treat agitation. introduction: patients with convulsive status epilepticus (cse) frequently require mechanical ventilation (mv), either for general anesthesia in case of refractory generalized cse, or for airway protection. guidelines for the management of refractory generalized cse currently recommend general anesthesia for - h, followed by gradual withdrawal. our objective is to evaluate the incidence of refractory generalized cse among patients who required mv during pre-hospital management of status epilepticus, and to describe the management of general anesthesia in intensive care unit (icu). this ongoing multicenter retrospective observational study is conducted in french icus. all patients admitted in icu under mechanical ventilation between - - and - - with disease-code "status epilepticus" are included. exclusion criteria are-age < years, post anoxic se, acute traumatic brain injury, initiation of mv in icu, transfer from another icu, inclusion in a therapeutic trial on se, non-convulsive se. collected data include reason for mv, antiepileptic treatment, dosage and duration of general anesthesia, mode of eeg monitoring. outcomes are-relapse of se, mv duration, in-icu length of stay and mortality. results: among the medical files reviewed, met the inclusion criteria and were analyzed, and were excluded. a minority of patients ( . %) had a refractory generalized cse, most patients ( . %) had a non-refractory generalized cse + the others had mostly partial cse. the main reason for intubation was coma (n = , . %). the duration of general anesthesia was not significantly different in refractory cse patients compared to non-refractory cse patients (p = . ). data regarding main outcomes are summarized below-. these preliminary data suggest that the majority of the patients admitted in icu under mv for cse do not have a refractory status. indication of mv is mainly coma without persistent convulsions. the mean duration of general anesthesia before withdrawal is < h, and thus in discrepancy with guidelines, but does not seem associated with a frequent relapse of se. if this low rate of rse for patients admitted in icu and the safety of rapid withdrawal of ga are confirmed, the recommended - h duration of general anesthesia in icu could be challenged. introduction: induced coma in intensive care patients protect them against pain and neurologic disorders. however, a few of them may present a delayed wake-up when the sedation is interrupted. the aim of this work is to assess brain imaging findings in patients with this condition. patients and methods: retrospective review of imaging data of patients ( males and females), aged between and years, admitted in intensive care unit (icu) between june and september , who had sedation or general anesthesia and presented a delayed wake-up. they were explored either by mri (n = ) or computed tomography (ct) (n = ). patients with traumatic lesions were excluded. results: patients were admitted in the icu because of chronic obstructive pulmonary disease exacerbation (n = ), infectious pneumonia or pleural effusion (n = ), acute respiratory failure (n = ), heart disease (n = ). two patients underwent general anesthesia. septic shock and circulatory collapse occurred in and patients respectively. mri and ct showed lesions that may explain the wake-up delay in of and of patients, respectively. brain anomalies included anoxic lesions (n = ) with basal ganglia involvement (n = ), ischemic or hemorrhagic strokes (n = ), hepatic encephalopathy (n = ) and herpetic encephalitis (n = ). conclusion: brain imaging techniques help diagnosing causes of delayed wake-up after induced coma. anoxic lesions and strokes are mostly behind this condition. mri is more accurate than ct. introduction: gastric tubes are common in intensive care units used for enteral feeding, administration of drugs or aspiration of the digestive tract. these tubes offer an excellent tolerance but malposition may have serious consequences that can lead to patient's death. the actualy gold method to confirm their correct placement is chest x-ray. we report a study which evaluate the performance of gastric ultrasonography for the validation of the good positioning of the gastric tube. we carried out a prospective, monocentric study in a medical intensive care units. for each included patient, we compared the results of a gastric ultrasonography to the interpretation of a chest x-ray. results: one hundred and thirteen gastric ultrasonographies were performed from july to may . in cases, ultrasonography concluded that the gastric tube was correctly positioned, confirmed by chest x-ray. in cases, ultrasonography did not visualize the tube in gastric area. among these cases, only malpositions were detected by the chest x-ray. the sensitivity and specificity of gastric ultrasonography were . [ . + . ] and [ . + ]. positive and negative predictive values were and . , respectively. the ultrasonography was performed min [ . + . ] after the gastric tube placement while the chest x-ray was interpreted min [ . + . ] after this same placement (p < . ). our results suggest a good performance of gastric ultrasonography to check the positioning of the gastric tube. this result must be interpreted with caution because of a low power of the study. we planned a multi-center study to confirm our results. giabicani mikhael introduction: prognosis of cirrhotic patients hospitalized in intensive care unit (icu) remains poor. in many icus, cirrhotic patients are widely admitted and revalued after receiving optimal treatments. little is known about risk factors involved in the evaluation of the prognosis at day , except the persistence of organ failure. this susceptibility to organ failure would be related to an alteration of the regulation mechanisms of the systemic inflammatory response. the blood neutrophil-to-lymphocyte ratio (nlr) is an inflammation biomarker reported to predict clinical outcome in unselected critically ill patients and in patients with stable liver cirrhosis, but has never been studied in critically ill cirrhotic patients. the aim of this study was to evaluate the blood nlr as parameter to predict mortality of cirrhotic patients hospitalized > days in icu. retrospective monocentric study including consecutively cirrhotic patients hospitalized in a medical icu from to . for each patient, clinical and biological data at admission and day were collected. nlr at admission ("nlrd "), at day ("nlrd ") and its variation between admission and d ("delta nlr") were calculated. statistical analysis used appropriate non parametric tests and cox regression for survival analysis. the ability of the variables to discriminate survivors from non-survivors was determined using roc curves and a net reclassification index (nri). results: patients (median child-pugh score = [ - ], median meld score = [ - ]) were hospitalized more than days in icu. the major causes for icu admission were sepsis ( . %), gastrointestinal bleeding ( %) or respiratory failure ( . %). patients were followed up for . d . ( %) patients died- ( %) in icu, ( %) after icu discharge and ( %) after hospital discharge. in univariate analysis, factors significantly associated with mortality wereat d , nlr, meld and sofa scores + and between d and d -delta nlr, delta sofa and delta meld. predictors of death in multivariate analysis are shown in table . area under delta nlr roc curve was . (ci = . - . ). nri revealed that delta nlr was more efficient than delta sofa (nri = . %) to identify patients with a % mortality risk at least. conclusion: nlr is a novel inflammation index known to predict poor clinical outcomes. delta nlr is an independent predictor of mortality in critically ill cirrhotic patients and could be more effective than delta sofa in predicting hospital mortality in these patients. severe liver dysfunction acute liver failure related to exertional heatstroke: outcomes, histological features and role of liver introduction: severe acute liver injury and failure (sali alf) is a grave complication of exertional heatstroke (eh). liver transplantation (lt) may be a therapeutic option, but the criteria for, and timing of, transplantation have not been clearly established. the aim of this study was to define the profile of patients who require transplantation in this context. this was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related sali alf with a prothrombin time (pt) lower than %, with or without hepatic encephalopathy. results: male patients (median age- . years) with ali alf related to exertional heatstroke were studied + nine of them ( . %) were listed for emergency lt. the latter differed from those who were not listed with respect to their more severe liver failure after d , a clear deterioration in their pt and alt values between d and d , and more marked organ dysfunction. four of these nine patients were subsequently transplanted. at the time of lt, all had pt levels lower than %, a marked rise in bilirubin levels and required support for at least one organ (or x organs were involved). histological findings on the explanted livers demonstrated massive or sub-massive necrosis and little potential for effective mitosis with a mitonecrotic appearance. the unlisted patients ( . %) were still alive months later and had not experienced any after-effects. conclusion: survival without liver transplantation in patients with heatstroke-related ali alf reaches . %. the indication for liver transplantation is based on an evolving dynamic. the lack of any signs of an improvement in liver function at or after d , in patients presenting with other organ dysfunctions or failure, means that liver transplantation should be envisaged. the peculiar histological features observed on all the explanted livers, and the aspect of abortive mitoses in hepatocytes could be attributed to the effects of heatstroke. . on admission, the mean pt was . % ( - ), the mean total bilirubin was umol l. paracetamol poisoning was the principal etiology with % of the patients- % in the prometheus group versus % in the standard group (p = . ). the hepatic encephalopathy grade was significantly higher in the prometheus group- versus . in the standard group (p = . ). there was no difference between the two groups concerning mortality on day (p = ) or day (p = . ). there was no difference concerning the length of stay in intensive care unit or in hospital between the two groups. patients ( . %) were transplanted. there was a statistical difference between the two groups concerning liver transplantation (p = . )- transplant ( %) in the prometheus group versus transplant ( %) in the standard medical care group. there was a significant improve of encephalopathy after the prometheus session (p = . ). therapy in our icu were included consecutively and prospectively in the cohort. mars ® therapy performed using a double lumen dialysis catheter in the femoral or jugular vein. we used the monitor mars ® tc (teraklin) coupled with the dialysis machine prismaflex ® (gambro). the albumin dialysate circuit consisted of ml of % human albumin and was regenerated by an anion-exchange column and an uncoated charcoal column (diamars ® ie , diamars ® ac ). results: ninety patients were included for sessions. the mean duration was h min (± h min). the population treated consisted of groups-acute-on-chronic liver failure (aoclf), acute liver failure (alf), post-surgery liver failure (post transplantation, post hepatectomy), refractory pruritus and drug intoxication ( fig. ). regarding biological efficacy-total bilirubin was lowered in aoclf and post-surgery groups (p < . ), also in the alf group although not significatively. meld score was lowered in the aoclf and alf group (p < . ). however clinical variables (glasgow score and encephalopathy) didn't improve significatively. in the refractory pruritus group, pruritus decreased in out of patients (p < . ). bile acid levels decreased to . % of its mean baseline level (p < . ). in the drug intoxication group improvement of the richmond agitation-sedation scale (rass) from deeply sedated (rass < = − ) to minimal sedation (rass > = − ) was obtained in out of patients. out of sessions, catheter-related adverse effects were low ( . %), thrombocytopenia was the main adverse effect ( . %). conclusion: we report our mars ® experience with the largest cohort of patients referred from a single hospital. we showed biological efficacy in all indications, although clinical efficacy was uneven. mars ® therapy in patients with refractory pruritus yielded promising results. tolerance was good and the main adverse effect was thrombocytopenia. global transplantation-free survival was low in patients with liver failure, reinforcing the need for a liver transplantation center when using mars ® . introduction: colonoscopy is crucial for the management of lower gastro-intestinal disorders, but its profitability is discussed in critically ill patients, mainly because of the complexity of colonic preparation. as the profitability of colonoscopy in intermediate or intensive care units (cicu) has been scarcely reported ( ), we investigated its indications and usefulness. patients and methods: retrospective bicenter observational study ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . main endpoint: diagnostic profitability of cicu in unselected critically ill patients. profitability was a priori defined as "high" if cicu led to adapt ongoing therapies; allowed an endoscopic intervention; or participated in the decision to limit therapeutic effort. secondary endpoints: describe the quality of cicu and its preparation; determine its position in diagnosis strategy; describe its morbidity. ) + investigation of a gram negative bacilli sepsis (n = , %) + sigmoid volvulus (n = , %) + and cancer diagnosis (n = + %). cicu profitability was deemed high in % (n = ), with an endoscopic intervention performed in % (n = ). the cicu lead to antimicrobial adaptation (n = ), emergent surgery (n = ), or to limit therapeutics effort (n = ). in cases ( %) the cicu was considered normal. patients' preparation was rated as good in % (n = ) + and the colonoscopy was complete in ( %). the cicu was mainly performed as a nd ( %) or rd ( %) investigation after an abdominal ct-scan or an upper digestive endoscopy (respectively performed in first instance in and %). three cicu were complicated by hemodynamic and respiratory failures, none were fatal. discussion: in our series of unselected critically ill patients, cicu were mainly performed to investigate lower gastro-intestinal bleeding. despite a low rate of good preparation, cicu is safe and its profitability is high in the majority of cases. conclusion: although performed in poor conditions, cicu seems useful in the diagnostic and the therapeutic management of critically ill patients, and not only in gastro-intestinal bleeding. ( ) church, surgical endoscopy . introduction: accurate pain assessment is associated with better outcomes in intensive care unit (icu) patients. specific scales for noncommunicative patients have been developed and validated but their routine use still remains inaccurate and subjective. analgesia nociception index (ani) is based on high-frequency heart rate variability. this study objective was to assess the correlation between the behavioral pain scale (bps) and ani during care procedures in deeply sedated patients. we conduced a french multicentric prospective observational study with blinded continuous recording of ani during h with spotting of care procedures in patients with rass less or equal to − . we compared pain assessment using bps and ani before (t ) and during (t ) each care procedure. the cares analyzed included prick glycaemia, turning, catheter insertion, dressing change and others. a behavioral pain reactivity (bpr) was defined by a bps elevation of at least point. we analyzed minimal ani values and its variations with calculation of deltaani (anit -anit ). because of the analysis of several cares per patient we used a bonferroni's correction in comparison of bpr and no bpr groups with a significant p value < . for this comparison. for others analyses the p value considered as significant was p < . . correlation between ani and bps was analyzed using a spearman correlation rank test. introduction: the pain associated with burn was one of the most painful injuries to treat. pain was induced by therapeutic acts such as wound debridement, dressing and other painful procedures. burn pain caused changes in neurophysiology and pharmacokinetics that may make standard pharmacologic analgesic therapy less effective than usual.virtual reality has been explored as an adjunct therapy for the management of acute pain for a number of conditions. in our study, we attempt to assess the impact of virtual reality on management of burn pain during dressing changes. patients and methods: before the therapeutic procedure (dressing changes), the concept of virtual reality therapy was explained to the patient (technology and equipment used). the video used was snow mountain. during the act, pain was assessed until the end of the procedure. the assessment of pain was based on visual analog scale (vas). for pain intensity, the scale was most commonly anchored by "no pain" (score of ) and "very intense pain" (score of ). results: during the study period, patients were included. the mean age was ± years. % of our patients were adults aged over years. they were men and women. the average burned surface area was ± %. pain was evaluated before the start of the therapeutic procedure. the mean initial pain severity score was . ± . (range to ). the pain assessment after virtual reality condition showed a significant decrease in the intensity of pain (p < . ). the mean pain decreased from . to . ± . with extremes ranging from to . conclusion: our study supports the use of virtual reality, simple noninvasive, as an adjunct therapy in the management of pain associated with dressing changes in burn patients. introduction: hypno-analgesia (ha) is used in the operating room and for complex pain. before implementation of ha in our intensive care unit (icu), most protocols for algogenic procedures included intravenous or epidural morphine and nitrous oxid. since , many caregivers have been trained, ha has been implemented and patient comfort is evaluated using ) a specific analogic scale of comfort ( to ) before and after the procedure + ) at the end of the procedure, a score of patient and caregiver comfort using a five item questionnaire ( to points). this pilot prospective study compares ha versus the standard protocol in the removal of abdominal drains after digestive surgery. the main objective was to evaluate the patient comfort before after the procedure using a scale of comfort + the secondary objectives were to test the patient and caregiver comfort scores and evaluate in the impact on consumption of analgesic. between may and september , two groups were obtained, according whether the procedure was performed by ha-trained or non-hatrained professionals (depending on caregivers availability in the unit). the number of subjects required to compare scales of comfort before vs. after drain removal was , using a nonparametric wilcoxon-mann-whitney test. results: eighty-eight patients were analyzed. the mean note in the comfort scale remained unchanged after vs. before drain removal in patients without ha (n = , + . points, ± . ), while it increased in patients with ha (n = , + . , ± . + p = . ). using our specific five item comfort score, patients and caregivers had a comparable level of satisfaction in ha and non-ha groups (patients . and . + caregivers- in both). a trend was observed in reduction of the consumption of morphine and nitrous oxid with ha, without altering their comfort. discussion: despite its limitations (mainly, its open non-randomized design), this study suggests that-ha may be used for algogenic procedures and is willingly adopted in icu by patients and professionals + specific scales scores, adapted for ha, may be useful to assess the effectiveness + finally, ha seems to be at least as efficient as classical procedures and could reduce the use of analgesic drugs. conclusion: ha adds value to patients and to all caregivers. prospective randomized studies are needed to valid the comfort scores we proposed, and to prove that ha reduces the consumption of analgesic drugs. introduction: pain has long been a focus of concern for doctors and caregivers. in intensive care unit, the inability to verbalize discomfort and pain are major stressors for patients. music therapy has demonstrated in many international studies its effect on the blood pressure and on the respiratory frequency. in this context, we conducted a study to evaluate the effects of standardized musical intervention on pain during painful cares in vigils patients hospitalized in critical care. patients and methods: design-we conduct a prospective, observational, randomised, single blind, mono center study. painful cares were studied and then distributed in two groups (n = with music, n = without music). the patients were equiped with a bose© helmet, and had or not music therapy during the care. our main criteria was the pain, it has been evaluated by a numeric scale before and after the painful care. we also estimated anxiety with the covi's heteroevaluation scale before and after the car. we also noticed if the care were stopped because of the pain, then we used a semi quantative numeric scale in order to estimate the feeling of the caregiver and the patient on the session. results: concerning pain, there is no significant difference between the two groups (p > . ). however, in the music group, pain decreased by % after the care (p < . ). anxiety was way lower in the music group than in the group without music (p < . ). we also noticed a decrease of % of the anxiety in the music group. the patients and the caregivers' feeling were the same in the two groups, with no significant difference (p > . ). on the other hand, caregivers tended to underestimate the difficulty of the session in comparison with the patients' (p < . ) in both groups. conclusion: music therapy did not improve the pain in a significant way, in the music group versus the group without but allowed a decrease of % of the pain after the care. nevertheless, music reduced by two patients'anxiety. introduction: sedation and analgesia is one of the basic themes in icu as complications associated with excessive sedation negatively impact the morbidity and mortality of patients. the objective of this study is to show that the nurse implementation of a sedation and analgesia algorithm is beneficial to the patient in terms of sedative drugs reduction and thus overall decrease in duration of mechanical ventilation (mv) and the morbidity and mortality which is associated with it, without altering patient comfort and tolerance of the environment. patients and methods: a before and after prospective, observational, non-interventional study was conducted in surgical icu in caen university hospital, between november and april . mechanically ventilated patients under sedation predicted to last h or more were included. during the "before" period, sedation and analgesia was managed by the physician, while during the "after" period, it was managed by the nurses according to the protocol. results: intubated and mechanically ventilated patients were admitted during the study period. among the eligible patients, were included during "before" period and during "after" period. the duration of mv after inclusion was significantly shorter in group "after" ( . [ + ] vs [ + . ] days, p = . ), as the duration of target rass (- à ) was significantly longer ( the patients experienced less of ventilator-acquired pneumonia (vap) and delirium during the "after" period ( vs . %, p = . , and vs . %, p = . , respectively). the nurse implementation of a sedation and analgesia algorithm was associated with a trend towards reduction in duration of mv, icu and hospital length of stay. moreover, prevalence of vap and delirium was reduced, in correlation to the significant decrease in sedative drugs. this type of algorithm is necessary to reduce morbidity and mortality associated with mv. introduction: central venous catheter insertion is a common practice for anesthetists and intensivsts. this invasive procedure generates pain and anxiety for patients. we aim to demonstrate that remifentanil improves the analgesia during scheduled central venous catheter insertion in mindful patients. patients and methods: a prospective, randomized, double-blind, controlled study in patients requiring central venous access. patients were randomly assigned to receive ng ml − remifentanil target controlled infusion (tci) and local anesthesia (la) with lidocaine or placebo and la. all patients were monitored in intensive care or postintervention care unit and systematically received oxygen. patients were asked to assess verbal numeric rating pain scale (vnrps) during the procedure. the primary outcome was the maximal vnrps. secondary outcomes were pain at each step, anxiety, patient satisfaction, operator ease and side effects. results: ninety patients were included ( in each group). all patients were analyzed. remifentanil significantly reduced maximal pain-vnrps ( % confidence interval [ci] - ) vs ( % ci - ) in the placebo group p = . (table ) . we did not observe any adverse event during this study, and there were no significant difference between the groups regarding side effects. conclusion: tci remifentanil is a safe procedure to reduce pain during central venous catheter insertion in awake patients. trial registration-clinicaltrials.gov identifier- , remidolcath. introduction: although guidelines on post-resuscitation care recommend the use of short-acting agents for sedation during targeted temperature management (ttm) after cardiac arrest (ca), the potential interests of this strategy have not been clinically demonstrated. patients and methods: before-after study. we compared two sedation regimens (propofol-remifentanil, period p vs midazolamfentanyl, period p ) among comatose ttm-treated ca survivors. management protocol, apart from sedation and neuromuscular blockers use, did not change between the two periods. baseline severity was assessed with cardiac-arrest-hospital-prognosis (cahp) score. time to awakening was measured starting from discontinuation of sedation at the end of rewarming. awakening was defined as delayed when it occurred after more than h. results: patients ( in p , in p ) were included. cahp score in p and p did not significantly differ (p = . ). sixty percent of patients awoke in both periods ( vs , p = . ). median time to awakening was . (iqr - ) hours in p vs. (iqr - ) hours in p . awakening was delayed in % in p vs. % of patients in p (p < . ). after adjustment, p was associated with significantly lower odds of delayed awakening (or . , % ci . - . + p < . ). patients in p had significantly more ventilator-free days, and lower catecholamine-free days between admission and day . survival and favorable neurologic outcome at discharge did not differ across periods. time course for awakening according to sedation period. these figures report the time course of patients included after discontinuation of sedation. at each time point, we report in the upper part, proportion of patients awoken after discontinuation of sedation, in the lower part, patients who died without awakening, and in the middle part (in white), patients still comatose. red dots indicate, for each period, the last patient awakening (after days in p and days in p ). black dots indicate the median time to awakening (too early to appear for period ). conclusion: during ttm following resuscitation from ca, sedation with propofol-remifentanil compared with midazolam-fentanyl was associated with an earlier awakening, and an increase in ventilator-free days. the new recommendations of the french society of anesthesia-intensive care (sfar) on perfusion and medication errors were revised in to promote proper use relating to drug administration with medical devices. to advance that of inquiry, practices of our intensive care unit (icu) were assessed in order to improve drug administration by central venous catheter (cvc). patients and methods: prospective evaluation by pharmacist resident and technical nurse during seven weeks, using a standard evaluation tool, in a bed icu. drug recommendations and sfar documents from were used as referential of conformity. the following parameters were evaluated- central venous lines mounting, drug administration and identification with a focus on narrow therapeutic index (nti) drugs. results: patients with cvc were analyzed between june and july . entered directly in the icu. were hospitalized for surgical reasons. had triple-lumen cvc. regarding the first parameter, no conformity was found due to lack of line identification ( %) or anti-return valve well positioned ( %). perfusion ramp position was above heart level in %, infusion tubing had contact with floor in %, and absence of plug on non-used lines is found in % of cases. regarding second parameter, non-conformities were due mostly to syringe label-absence of drug's concentration ( %), preparator identification ( %), patient identification ( . %), drug identification ( . %, all concerning propofol), date and time of medication preparation ( %), lack of color code of labels ( %). regarding nti, % were not administrated according to the recommendations-absence of dedicated line ( %), absence of administration on the nearest insertion site of the catheter ( %). conclusion: the evaluation highlight some improvement axis such as complete identification on syringes, sensitizing of icu healthcare team, or homogenization of cvc perfusion system. it calls for a second evaluation round after implementation of improvements. introduction: sedation is a corner stone of the care of patients receiving mechanical ventilation in the icu. sedation was associated with increased comfort and adherence to care, but also with increased morbidity, including delirium, increased duration of mechanical ventilation and length of icu stay. previous studies reported beneficial impact of reduced doses of sedative drugs and careful monitoring of patients comfort and consciousness. our goal was to assess the impact of the introduction of a nurses-dedicated sedation protocol in our icu. patients and methods: this monocentre retrospective before-after study included all the patients admitted in our icu, over two threemonth periods, from july and january , treated with invasive mechanical ventilation for more than h and older than yrs. after the first period, all physicians and nurses were trained to a new sedation management protocol. analysis was performed to assess the prescription and application of the protocol, its impact on the use of sedative drugs, icu length of stay, and duration of mechanical ventilation. major complications were also recorded. results: patients were included- before and after the protocol implementation. patients in both groups had similar baseline characteristics (men vs. %, p = . + mean age ± vs. ± years, p = . + weight . ± . vs. . ± . kg p = . + igs ± vs. ± , p = . + medical admission vs. %, p = . ). recordings of rass and bps did not differ between groups ( ± vs ± , p = + ± vs, ± , p = . ). the duration of sedation was significantly shorter after introduction of protocol ( . ± . vs . ± . , p < . ), as was the duration of mechanical ventilation ( . ± . vs . ± . , p = . ) and icu length of stay ( . ± . vs . ± . , p = . ). there was no difference in major icu complications, nor in mortality between groups ( and %). conclusion: although the implantation of a sedation protocol did not translate in increased recording of rass and bps scores, it was associated with improved outcomes. our data suggest that, more than the protocol by itself, beneficial effects reported after the implementation of a sedation protocol may be ascribed to increased awareness of the care givers and thus better management of sedation. introduction: workload affects the quality of care and the prognosis of critically ills patients. measuring workload in intensive care units (icu) has thus become essential for allowing a better matching between the activities required and the management of resources. in march , the medical icu of the university hospital of monastir (tunisia) moved into new buildings (more space and beds, computerbased prescriptions and monitoring, etc.). the aim of the present study is to compare the level of workload before and after the change of the icu buildings. patients and methods: during the two study periods (period -july-september and period -july-september ) adult patients consecutively admitted, for more than h, in the medical icu for arf and or sepsis were included in the analysis. data collected were the demographic characteristics (age, sex, body mass index (bmi), comorbidities, simplified acute physiology score (saps) iii), the nursing workload measured using the therapeutic intervention scoring system (tiss- ) and hospital survival. results: thirty-six patients ( male) were included in the study ( during period and during the second period). the medians of age, saps iii and bmi were respectively (iqr = ) years, (iqr = ) and . (iqr = . ). the main comorbidities were hypertension, copd and neurological disease respectively in , and %. the demographic characteristics were similar during the two periods. nurse workload was characterized by m tiss- = (iqr = ) and time of nurse's care of min (iqr = ). these two workload indicators were significantly higher during the second period (table ) . during the second period, "standard monitoring" and "frequent dressing changes" (> time day) were the activities with significant increase from, respectively to % (p < . ) and from to % (p < . ). the relocation of our icu in in new buildings was associated with a significant increase of the nurse workload with regard to patients with arf and or sepsis. . bland-altman analysis showed excellent accuracy and precision between recorded and collected data for all tested variables within clinically significant pre-defined limits of agreement. however, ( . %) data were missing and a delay was observed between videotaped and collected times. this delay was less than s and remained stable through all data for each patient. we identified that the missing data were due to a limit in the number of data being processed in the database at the same time and the delay between data presentation and data collection in the database was due to different server time settings. both technical issues were corrected. conclusion: our study identified two issues in the data collection process that slightly limited the accuracy of our high resolution electronic database. we recommend the performance of such validation study before using a high resolution database for clinical or research purposes. introduction: fluid overload, and also its variations, is known to jeopardize the outcome of icu patients. however, fluid balance remains difficult to assess accurately. in that context, our study aims to assess the prognostic value of body weight variations (bwv) from day to day on the -day mortality, length of stay (los) and the occurrence of ventilator-associated pneumonia (vap) and bedsore in critically ill patients with shock. patients and methods: adult patients admitted in icu with shock between and , and requiring mechanical ventilation during the first h, were extracted from a prospective multicenter cohort for a retrospective analysis. bwv was defined as the difference between the body weight of the day of interest and the body weight on admission. case mix, severity on admission, and outcomes were collected. fine and gray sub-distribution survival models were used, with icu discharge as competing event, adjusted on comorbidity and illness severity at admission at each landmark, from day to day . the impact of bwv on icu stay duration was estimated through a multivariate negative binomial regression model. the median age and saps score of the included patients were (iqr, - ) years and (iqr, - ), respectively. the bwv increased from . kg (iqr, - . ) on day to kg (iqr, − . to . ) on day . the day in-hospital mortality, the icu occurrence of bedsore and vap were , and . %, respectively. four categories of bwv were defined according to bwv interquartiles: weight loss, stable weight, moderate and severe weight gain. categories of bwv were independently associated with death on day and day (day : shr . ; % . - . p = . ; day : shr . ; % ci . - . , p = . ) (fig. ) . a weight loss tended to be associated with increased occurrence of bedsore, and weight gain with increased occurrence of vap. the extent of bwv increased the duration of icu stay independently of other severity factors. discussion: bwv may be another clinically relevant tool to assess the risk of death, mostly after day . the increased risk of bedsore in case of weight loss deserved to be confirmed. conclusion: body weight should be daily monitored for better prognostication. bwv-based restrictive strategies should be further evaluated. the clinical effectiveness of multi-layer silicone dressings in preventing icu acquired pressure ulcers: a randomised controlled trial introduction: the development of pressure ulcers (pu) in critically ill icu patients result in additional morbidity and may contribute to mortality in some cases. the minimisation of icu acquired pu remain an international challenge. this paper describes australian research that used multi-layer soft silicone sacral and heel dressings to prevent pu in critically ill patients. patients and methods: a total of critically ill patients were enrolled into an -month randomised controlled trial in one of melbourne's trauma centres. patients were randomised on admission to the emergency department and either had standard pu prevention or standard care plus the application of prophylactic sacral and heel dressings. patients were observed daily for pu development for the duration of their icu stay. results: patients in the dressing group has significantly reduced incidence rate of pu development compared to patients receiving standard pu prevention alone ( . vs . %, p < . ). patients in the dressings group had a relative risk reduction of % and a % absolute risk reduction for developing a pu regardless of their critical illness. results indicate the number needed to treat to prevent one pu was . additionally, we calculated the cost-benefit of this intervention and found the patients treated with prophylactic dressings cost . time less than the standard care group for wound care. discussion: the use of prophylactic dressings to prevent pu at our hospital have proved to be very effective in icu and subsequent studies have confirmed our results. it appears that the main mechanism of pu protection provided by these dressings is the reduction of pressure and shear forces leading to tissue distortion and cell death rather than the previously accepted ischaemic model of pu development. our current policy is now to use these dressings on all patients with a high risk of developing pu. the use of prophylactic multi-layer silicone dressings to prevent pu in critically ill patients is effective but it does not replace standard pu prevention methods. the use of these dressings sould be considered complimentary to best practice in pu prevention. iatrogenic events in intensive care unit: incidence, risk factors and impact on outcome ayed samia , merhebene takoua introduction: iatrogenic events (ies) are defined as harm resulting from medical intervention and health care, and not explained by underlying disease. mortality is reported to be as high as . % in cohorts of hospitalized patients experiencing ie. both length of stay and cost of hospitalization are increased by ies occurrence. we perform this study to determine the incidence, risk factors, and impact on outcome of ies in intensive care unit (icu). patients and methods: all patients admitted more than h to the -bed icu of a teaching hospital were prospectively screened. patients were monitored daily for adverse clinical occurrences. time and data about each ie were collected and they were considered as preventable or life-threatening events. for each patient, the followings were recorded-basic demographic data, indication for admission, severity scores on admission (sapsii and apacheii), need and duration of mechanical ventilation (mv), length of stay (los) in icu, intensive care work load score (omega), global mortality and ies related mortality. results: during the months period, patients were included and ( . %) were judged to have developed an ie while hospitalized. we recorded ies over days in icu so a density incidence of ie for patient-day. ies were considered preventable in % of cases and life-threatening in % of cases. ies occurred in a mean delay of ± days. global mortality rate was . % and ies related mortality rate was . %. patients with ies were significantly severe on admission, with a longer duration of mv and los in icu. omega score was significantly higher. multivariate analysis showed that omega score was the independent risk factor of ies occurrence (or . ic % [ . - . ], p < - ). dead patients were significantly severe on admission and experienced more ies than survivors. omega score, duration of mv and los were significantly higher. in multivariate analysis, ies and life-threatening ies were independent factors of mortality (or . ic % [ . - . ], p < - and or . ic % [ . - . ], p < - respectively). conclusion: ies in icu are common and frequent but one-third is preventable. work load icu score is the independent risk factor of their occurrence. ies impact largely the outcome especially the lifethreatening ones. efforts must be focused on preventing programs to reduce ies and improve the outcome. introduction: based on the recent sepsis- definitions, septic shock is defined by the combination of vasopressor requirement and serum lactate level > mmol/l. however hyperlactatemia and lactate kinetics may result from both increased production and impaired clearance in the critically ill, and may therefore not only rely on the severity of circulatory failure. we herein addressed the determinants of hyperlactatemia (> mmol/l) and the factors likely to impact on early lactate clearance in septic shock. patients and methods: this was a -year ( - ) monocentric retrospective study. all adult patients diagnosed for septic shock within the first h were included. septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. the first lactate value (l ) was measured at the time of icu admission. hyperlactatemia was defined as a first lactate level > mmol/l. the second value (l ) was measured within h following the first measurement. lactate clearance was calculated as (l -l ) l time between l and l measurements) and expressed in mmol hour. parameters associated with initial hyperlactatemia and lactate clearance were investigated using multivariate logistic regression analysis. introduction: cardiac surgery with cardiopulmonary bypass (cpb) induces immunosuppression which has considerable implications for patients. cpb induces a significant increase in circulating neutrophils. neutrophil activation, associated with production of antibacterial peptides, reactive oxygen species (ros), cytokines, and other inflammatory mediators, as well as release of dna into the extracellular milieu (neutrophil extracellular traps (nets)), plays a central role in innate host defense and modulation of inflammation. however, it has been shown that, in septic shock or systemic inflammation as major surgery, immature circulating neutrophils can induce immunosuppression and increase the risk of secondary infections. staphylococcus aureus (sa) is one of the most commonly encountered bacterial pathogen responsible for poststernotomy mediastinitis, and neutrophils alterations may favor postoperative infections. the main objectives of this study were to evaluate the direct effects of cbp on neutrophils functions and to study the impact of different strains of sa on neutrophils bactericidal functions. patients and methods: blood samples were collected before and h after cardiac surgery with cpb and bone marrow samples were harvested directly after sternotomy, before initiation of cpb, and at the end of cpb, before sternal closure. septic patients were included as controls. circulating neutrophils analysis was performed using flow cytometry. we also studied netosis, ros production and bactericidal activity in isolated neutrophils before and after surgery using two strains of sa-one responsible of postoperative mediastinitis and one isolated from nasal carriage. results: blood cell count with differential demonstrated a significant increase in neutrophils h after surgery. flow cytometry analysis of blood samples indicated neutrophils were matures with a significant increase in degranulation marker (cd b). neutrophils life span was also increased after cbp. flow cytometry analysis of bone marrow samples showed no difference in cell composition and maturation before and after cbp. the neutrophil production of ros was significantly higher after cbp. however, cbp did not impact nets formation, phagocytosis and bactericidial function. moreover, there was no difference regarding the phagocytosis and the bactericidial activity when exposed to the two strain of sa. as expected, immature neutrophils count was significantly increased in septic patients compared to cardiac surgery patients. these results indicate that cbp promotes the recruitment of matures neutrophils via a demargination process. cbp does not induce neutrophil dysfunction. neutrophils should not be targeted to decrease postoperative infection after cpb. introduction: protein tyrosine phosphatase b (ptp b) is a negative regulator of both no production and insulin signaling and has been shown to be an aggravating factor in septic shock. stress hyperglycemia frequently occurs in critically ill patients and is associated with poor outcome. experimental studies on transgenic mice have shown that ptp b deletion resulted in a reduced insulin resistance and in a better survival during experimental model of sepsis. the main objective was to study the correlation between the ptp b gene expression and organ failure (through the delta sofa score between day and day ) or insulin resistance. patients and methods: twenty-seven healthy male volunteers have been included in this clinical trial. the product was administered by continuous intravenous infusion (civ). a single ascending dose design with dose levels was used. cohorts and received a -min single dose of motrem ( and mg and one and two volunteers respectively). then, cohorts to received either a -min loading dose (from . mg kg to mg kg) followed by . -hours maintenance dose (from . mg kg h to mg kg h) of motrem or a matching placebo ( - ratio). all volunteers were carefully monitored. before escalation to the next dose level, safety and pk data of the previous dose level were reviewed by a safety review committee. since immune system is at rest in normal individuals and thus trem- pathway is not activated, no pharmacodynamics parameters were analyzed. the main objectives of this trial was then to study the safety and pharmacokinetic profile of motrem. results: no product related changes in vital signs, clinical nor laboratory parameters were observed. no product-related adverse events were reported. the pk of motrem was linear; the main clearance was estimated at l/h/ kg which is higher than the hepatic blood flow in human (i.e., l/h/ kg) and is therefore indicative of an extensive enzymatic metabolism in blood + effective half-life was calculated to be about min. conclusion: motrem was found to be safe and well tolerated up to the highest dose tested ( mg/kg for a -min loading dose and mg kg h for a . -hours maintenance dose). safety and pharmacokinetics of motrem is currently being studied in septic shock patients in a phase iia randomised, double-blind, two-stage, placebo controlled, international, multicenter clinical trial (www.clinicaltrials.gov nct ). - ) is an immunoreceptor expressed on neutrophils and monocytes macrophages whose role is to amplify the inflammatory response driven by toll-like receptors engagement. the pharmacological inhibition of trem- confers protection in several pre-clinical models of acute inflammation. in this study, we aimed to decipher the role of trem- on the endothelium. we evaluated the expression of trem- in vessels and isolated endothelial cells by flow cytometry, qrt-pcr and confocal microscopy. we generated an endothelium-conditional trem- ko mice and submitted them to polymicrobial sepsis through clp. organs and blood were harvested at different time points and analyzed for cellular content, cytokine chemokine concentrations, and vasoreactivity. survival was monitored for week. results: trem- was expressed in aorta and pulmonary vessels from animals, and inducible after lps stimulation or during sepsis. these results were confirmed in human pulmonary microvascular endothelial cells. the pharmacological inhibition of trem- , using the synthetic inhibitory peptide lr , decreased the lps-induced trem- expression. sepsis induced a profound vascular hyporeactivity in wt animals, both in terms of contractility and endothelium-dependent relaxation. although contractility was still impaired in endotrem- -mice, vasorelaxation was completely restored. soluble trem- concentrations, a marker of trem- activation, were markedly increased in the plasma, the peritoneal lavage fluid and the lungs from wt septic mice compared to control. in endotrem- -mice, strem- level was reduced. plasma concentrations of soluble vcam- and il- were also reduced in endotrem- -animals. we observed an accumulation of neutrophils and inflammatory ly chigh monocytes in the lung of wt septic mice. this accumulation was dampened in endotrem- -mice. by contrast, endothelial trem- deletion favored the accumulation of reparative cells (ly clow monocytes). finally, survival was clearly improved in the endotrem- -group as compared to the wt group. conclusion: we reported that trem- is expressed and inducible in endothelial cells and plays a direct role in vascular inflammation and dysfunction. the targeted deletion of endothelial trem- conferred protection during septic shock in modulating inflammatory cells mobilization and activation, restoring vasoreactivity and improving survival. the effect of trem- on vascular tone, while impressive, deserves further investigations including the design of endothelium specific trem- inhibitors. - . ]. patients suffered from pneumonia, from intra-abdominal sepsis. we measured serum levels of total and free thiamine, thiamine mono di and triphosphate (tmp, tdp and ttp respectively), as well as the erythrocyte transketolase activity and arterial lactate at the time of admission. we also recorded the vital status at the end of the icu stay. results: % of our subjects exhibited particularly low levels of free thiamine (< nmol/l). there was no correlation between free (r = − . ; p = . ), or total (r = − . ; p = . ) thiamine concentration and lactate levels. there was no correlation between tmp (r = . ; p = . ), tdp (r = − . ; p = . ), ttp (r = − . ; p = . ) and lactate levels in the whole population. no correlation was found between the concentration of thiamine derivatives and arterial lactate levels in the subgroup of patients exhibiting the highest levels of lactate (> and > mmol/l). total thiamine and tdp concentration at the time of admission were significantly higher in icu survivors than in non-survivors (p = . and p = . ). during sepsis, we did not find any correlation between thiamine and lactate concentration. lower thiamine diphosphate concentration may be associated with icu-mortality. introduction: a positive fluid balance in sepsis is a determining factor for mortality. in previous experimental studies, sodium lactate has been shown to improve hemodynamic and avoid fluid overload ( ). to understand these beneficial effects, we investigated the impact of sodium lactate on capillary leakage, in comparaison to saline on capillary leak in a rat model. the sixteen sedated, mechanically ventilated rats were challenged with intravenous infusion of e.coli lipopolysaccharide ( mg/kg). two groups of eight animals were randomised to receive a continous perfusion ( ml/kg/h) of sodium lactate . % (treatment group) or . % nacl (control group). in order to inject the same caloric load in the two groups, a . ml/kg/h of either water of % dextrose solution were perfused. mean arterial pressure, heart rate, urine ouput were measured over a min period. an echocardiography was then performed and evans blue ( %, mg/kg) was intravenously injected min before sacrifice. organs were withdrawn and organs wet dry ratio and evans blue dye extravasation were measured. results: fluid balance, organs wet dry ratio and evans blue dye extravasation were not significantly improved in sodium lactate group. hemodynamics parameters were not significantly enhanced after sodium lactate infusion. discussion: previously, lactate administration has improves renal perfusion. in our study, the volume of urine output was decreased in the groups reflecting the severity of our model. and the vascular filling ( . ml/kg/h) higher than in the literature could impact our results. ( ) recently, the pressure electricy index-pmus eadi index (pei) has been described. ( ) the purpose of this study was to assess muscular pressure (pmus) using pei with our nava protocol. patients and methods: observational study, patients recovering from pneumonitis and acute respiratory failure. sbt was pressure support ventilation with cmh of assist and no pep. pei was calculated under nava and during sbt from airway pressure drop during end-expiratory occlusions, muscular pressure (pmus) was estimated from pei ( ) . another index, patient ventilator contribution index (pvbc) was also measured using the inspiratory peak of eadi and vt (inspiratory) during assisted and non-assisted breaths. we calculated pvbc-squared because it has been shown that it is more correlated to pmus ptot. results: results are summarized in the introduction: in icu, intubation is a high risk procedure associated with high morbidity. despite procedure's improvement with systematic application of fluid loading, early use of vasopressors and checklist use, morbidity remains high. first pass success is strongly correlated with adverse event occurrence. a recent study by semler et al. concluded than "sniffing" position is better than "ramped" position to increase first pass success even the primary outcome prespecifiedpulse pressure saturation was not different between the two groups. we conducted a post hoc analysis of the randomized clinical trial macgrath mac video laryngoscope or macintosh laryngoscope for intubation in the intensive care unit (macman) to determine the best position for intubation in the icu. patients and methods: macman was a multicentre, open-label, randomized controlled superiority trial. consecutive patients requiring intubation were randomly allocated to either the mcgrath mac videolaryngoscope or the macintosh laryngoscope, with stratification by centre and operator experience. an only inclusion criterion was-"patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if-contraindication to orotracheal intubation (e.g., unstable spinal lesion); insufficient time to include and randomize the patient (e.g., because of cardiac arrest); age < years; pregnant or breastfeeding woman + correctional facility inmate; patient under guardianship + patient without health insurance; refusal of the patient or next of kin to participate in the study; previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess association between patient position (sniffing or supine) and first pass success. between-groups baseline difference was adjusted for baseline covariates significantly associated with the group membership (p < . ). results: failure of first pass introduction: during acute exacerbation of copd oxygen should be titrated to avoid both hypoxemia and hyperoxia. the recommendations are not followed and automated oxygen titration may be useful in this population. the aim of this study was to evaluate a new device developed to automatically titrate oxygen based on spo target (freeo , oxynov, canada) and to compare oxygenation parameters with usual administration (manual flowmeter). the study is an observational monocentric study. we prospectively included patients hospitalized for acute exacerbation of copd receiving oxygen. written informed consent was obtained from all patient. in the first part of the study, we evaluated oxygen flowrate and spo during min at baseline based on management of the physicians in charge. the oxygenation parameters were compared with automated titration (freeo during h). in the second part of the study, oxygen was delivered with freeo until oxygen weaning or a maximum of h. we evaluated the oxygenation parameters during prolonged utilization, the duration of oxygen administration, a new bluetooth spo connection compared to wire spo connection (evaluated by visual analog scale - ). results: we present preliminary data of copd patients (sex ratio m f = ). mean age (± sd) was ± years, mean fev (± sd) was . ± . l. oxygenation data in both parts of the study are displayed in the table . time in the spo target was significantly increased with freeo in comparison with manual titration and oxygen flowrate was reduced by half. in the second part of the study, the % of time in the spo target with automated oxygen titration was above % and time with hypoxemia and with hyperoxia were low. in patients, we compared comfort with wire spo connection to bluetooth wireless spo connection. the comfort was significantly increased with wireless connection ( . ± . vs. . ± . , p < . ). duration of oxygen administration after inclusion ( . ± . days) and hospital length of stay after inclusion ( . ± . days). conclusion: automated oxygen titration maintains the patients within predetermined spo target more than % of the time and reduces oxygen flowrate in comparison with manual oxygen titration. the second part of the study demonstrates the feasibility to use automated oxygen titration during several days with similar outcomes as previously reported in similar population. there are several limitations of the study and additional evaluations of this device are required. introduction: hyperoxemia occurs up to % of mechanical ventilation days in the icu [ ] and is associated with increased mortality as compared to patients ventilated in normoxemia [ ] . intellivent-asv is a full closed loop ventilation mode adjusting automatically oxygenation's settings fio and peep according to spo for passive and spontaneously breathing mechanically ventilated patients. this post hoc analysis of a monocentric randomized controlled parallel group study compared frequency of hyperoxemia (pao > mmhg and or spo > %) and hypoxemia (pao < mmhg and or spo < %) and the percentage of ventilation time with spo > % and the percentage of ventilation time with spo < % between intellivent-asv and conventional ventilation mode in mechanically ventilated icu patients. the randomized controlled trial was performed in the general icu of hôpital sainte musse, toulon, france. eligible participants were adult aged or over, invasively ventilated for less than h at the time of inclusion with an expected duration of mechanical ventilation of more than h. exclusion criteria were broncho-pleural fistula, ventilation drive disorder and moribund patients. patients were allocated to intellivent-asv group or to conventional ventilation group (volume assist control and pressure support modes) using blocked randomization. the post hoc analysis was performed by the comparison of all arterial blood gases (abg) performed during the study period-the number of abg with hyperoxemia and hypoxemia, the median pao and spo for these arterial blood gases and fio associated were compared according to group. results: patients were included, patients in each group. the total number od abg was (mode conventional) vs (mode intel-livent-asv) (p = ns). the number of abg with pao > mmhg was respectively versus (p = . ) with sao > % was vs (p = . ) with pao < mmhg was vs (p = . ) + with sao < % was vs (p = . ). the percentage of time of ventilation spent with spo > % was % vs (p = . ), and with sao < % was . vs . (p = . ). the continuous control of oxygenation settings provided by intellivent-asv decreases significantly the number of blood gas with hyperoxemia as compared to manual oxygenation setting without increasing the risk of hypoxemia. introduction: in invasively mechanically ventilated patient, dyspnea is frequent and severe. relying on self-report, its measurement remains challenging in patients unable to communicate. a -item observation scale, namely the intensive care-respiratory distress observation scale (ic-rdos), has been proposed as a surrogate of dyspnea-visual analogic scale (d-vas) self-report in intensive care unit (icu) patients [ ] . however this scale has been validated among non-intubated patients and included one item "supplemental oxygen" not thoroughly adapted for intubated population. we sought to develop a dyspnea observation scale more suitable for intubated patients and to evaluate its performance to detect dyspnea. patients and methods: ancillary analysis of data prospectively collected from icu communicative patients enrolled for the validation of the ic-rdos. factorial principal component analysis was first performed to select variables that mostly contributed to the principal axes, among a set of observable variables with possible clinical relevance. to identify the best correlation between these variables and d-vas, were performed an iterative partial least square regression process (pls). iterative pls procedure identified five variables, of which the combination and weighting allowed optimal correlation with d-vas (r = . ; % ci . to . ; p value < . ), which constitute the ic-rdos [ ] . in a first step, we removed "supplemental oxygen", not relevant in intubated patients. we obtained a -items ic-rdos (r = . introduction: lung ultrasound (lus) has emerged in different clinical settings, such as in intensive care medicine (icm). early diagnosis of ventilator-associated pneumonia (vap) remains a challenge to the intensivist. however, scientific evidence is little available on whether lus reliably improves the diagnosis of vap. the aim of this prospective study was to assess whether lus could be an alternative to pulmonary computerized tomography (ct) for assessing diagnosis of vap in icm. patients and methods: twenty-one patients ventilated for duration more than days suspected of vap were included. lus was performed by a well-trained operator who was blinded of the vap diagnosis. the diagnostic gold standard of vap was on the basis of pulmonary ct and positive culture pulmonary. all clinical criteria for the diagnosis were collected the same day of lus and pulmonary ct. the ultrasound exam included anterior, lateral and posterior views from both sides of the chest with superior and inferior views. we classed patient in groups according diagnosis of vap with pulmonary ct (vap + or vap-) and lus (lus + or lus-). lus characteristics of vap diagnosis included profils-asymetric line b (profil a b), without sliding (profil b'), sub pleural consolidation (profil c), consolidation with punctiforme bronchogram (pb), linear air bronchograms (lb) or dynamic bronchograms (lbd), posteror lateral alveolar pleural suffusion (plaps), pleural effusion pathological (pep), shred sign (ss and complications according to insertion site. the advantage of this method is that it gives a pragmatic view of the real clinical situation. patients and methods: ancillary study of the akiki trial, an open pragmatic randomized controlled trial published in , in which patients with severe acute kidney injury were randomly assigned to either an early or a delayed rrt initiation strategy. the present study involved all patients who underwent at least one rrt session. number of rrt catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected. results: among the patients included in akiki, received rrt at least once and patients were finally included in the analysis ( missing data), leading to a total of rrt catheters. femoral site was chosen preferentially (n = , %), followed by jugular site (n = , %) and subclavian site (n = , %). investigating center was the sole factor significantly associated with the choice of insertion site in multivariate analysis (p = . ). higher weight did not affect choice of insertion site. mean duration of catheter use was . (+- . ) days without difference according to site. catheter dysfunction was the main reason for replacement (n = , %). suspicion of infection led to replacement of many catheters (n = , %) but was actually seldom proven (n = , % introduction: long standing dialysis (sled or crrt) allows a better hemodynamic tolerance as well as a greater performance to achieve a negative fluid balance in intensive care unit. dialysis alter hemodynamics mainly by short term variation of blood volume. in this study we took advantage of a continuous monitoring of blood volume during dialysis session to decipher the relationship between the variation of relative blood volume (rbv) with mean arterial pressure (map). this study is observational prospective, including all prolonged (> h) dialysis sessions in saint etienne nephrology intensive care unit between january and june . exclusion criteria were ongoing blood transfusion and blood volume controled ultrafiltration. medical records were compiled along with cardiac ultrasonography at the beginning when available. the statistical analysis was perfomed in two parts. the first part studied the performances of the first hour deltarbv (defined by rbv before minus rbv after h of dialysis) to predict a drop of map below mmhg (hypotension). this analysis excluded sessions with hypotension and intervention during the first hour. the second study was the modelization of the relationship between deltarbv and deltamap for every hour of dialysis without any intervention on blood pressure. both analyses were performed using mixed effects linear and generalized models. fig. vancomycin pk during sled results: a total of sessions on different patients were performed during the period. the characteristics of patients were as follows-sex ratio at , age (sd) . ( . ), weight . kg ( . ), sapsii score . ( . ) . patients on were taken in charge for fluid overload. in the first set of analyses (per sessions), sessions were excluded for intervention in the first hour. the adjusted deltarbv did not predict hypotension during the session (generalized mixed effect model, session and patients set as random effects, estimate . , p = . ). in the second set of analyses (per hour without any intervention), h were analyzed. adjusted deltarbv correlated strongly and inversly with deltamap (linear mixed effect model, random effects were sessions, patients and hour order in the session, estimate . , p < . ). conclusion: in our mostly fluid overloaded patients, the drop of rbv correlated with an increase of map. introduction: kidney transplant recipients (ktr) are at risk of icu admission because of prolonged immunosuppressive therapy and a higher risk of cardiovascular events, severe infections or drug-related toxicities. several retrospectives studies reported the short-term outcome of ktr admitted to the icu, but data concerning the risk of chronic kidney disease and anti-hla immunization are scarce. patients and methods: in this retrospective study, we addressed the in-hospital and long-term mortalities of the ktr admitted in a french icu ( beds) between january and june . predictive factors for death, long-term renal function and hla immunization were identified. results: the main causes for admission were acute respiratory failure ( . %), sepsis ( . %), post-operative period (peritonitis, hemorrhage + %). at the admission, mean age, saps and sofa score were ± years, ± and . ± . , respectively. renal replacement therapy, mechanical ventilation and vasopressors were required in ( . %), ( . %) and ( . %) patients. immunosuppressive regimen was modified in patients ( . % + steroids increase %, calcineurin inhibitors or antimetabolites withdrawal and %, respectively). in-hospital mortality was % ( . and . % at months and ). by multivariate analysis, ebv blood proliferation in the months preceding the admission in the icu, and the saps gravity score at admission independently predicted the in-hospital and long-term mortalities. among the patients alive at month after the admission in the icu and with available data, ( . %) and ( . %) progressed to a more severe ckd stage at months and , respectively. both, the severity of the aki and the preexisting ckd predicted the risk of progression of the ckd. last, de novo anti-hla immunization at month was identified in patients ( . %, donor specific antibodies ( . %)) and was significantly associated with the occurrence of acute transplant rejection (p = . ). in five patients who developed anti-hla antibodies, rbc transfusion during the icu stay was the only immunological trigger identified. discussion: outcome of ktr is closed to the general population admitted in icu and better than other immunocompromised patient, like patients from oncohematology. conclusion: worsening of the renal function and hla immunization are frequent and may impact mid to long-term prognosis because of the high risk of transplant rejection, end-stage renal disease and further transplantation contraindication. introduction: acute kidney injury (aki) is associated with a poor prognosis. although pulmonary embolism (pe) may promote aki through renal congestion or hemodynamic instability, its frequency as its impact on the prognosis of patients with acute pe have been poorly studied. patients and methods: using data from the registro informatizado de la enfermedad tromboembolica venosa (riete) registry, we assessed the frequency of aki at baseline, and its influence on the -day mortality rate of patients with objectively confirmed pe. aki was defined according to the "kidney disease-improving global outcomes" definition. we used multivariate analysis to assess whether or not the presence of aki independently influenced the risk for -day death. the study included , patients with acute pe, of whom ( . %) had aki at baseline. of these, patients ( %) were in stage , ( . %) in stage and ( %) in stage . the proportion of patients with high-risk pe in those with no aki, aki stage , aki stage and aki stage was- . , . , . and %, respectively (p < . ). after days, patients ( . %) had died. overall mortality was- % in patients with no aki, . % in aki stage , % in aki stage , % in aki stage , all p < . ). on multivariable analysis, aki was independently associated with an increased risk of death at days (odds ratio = . + % ci . - . ), after adjusting for the initial severity of pe, age > years, chronic heart failure or chronic lung disease, cancer, anemia and liver cirrhosis. conclusion: one in every - patients with acute pe had aki. moreover aki was an independent predictor of poor outcome in pe patients. this study suggests that pe (and its severity) should be considered as a risk factor for aki and aki may deserve to be evaluated as a prognostic factor in patients with acute pe. introduction: metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (ohca). we aimed to identify risk factors and assessing the impact of metabolic acidosis on outcome after ohca. patients and methods: we included all consecutive ohca patients admitted between and . using admission data, metabolic acidosis was defined by a positive base deficit and was categorized by quartiles. main outcome was survival at icu discharge. factors associated with acidosis severity and with main outcome were evaluated by linear and logistic regression, respectively. results: patients ( . % male, median age years) were included in the analysis. median base deficit was . [ . , . ] meq/l. male gender (p = . ), resuscitation duration (p < . ), initial shockable rhythm (p < . ) and post-resuscitation shock (p < . ) were associated with a deeper acidosis. icu mortality rate increased across base deficit quartiles ( . , . , . and . %, p for trend < . ) and base deficit was independently associated with icu mortality (p < . ). the proportion of cpc patients among icu survivors was similar across base deficit quartiles ( . , . , . and . %, p = . ) and . % of patients with a base deficit higher than . meq l survived to icu discharge with a good neurological recovery. severe metabolic acidosis is frequent in ohca patients and is associated with poorer outcome, in particular due to refractory shock. however, we observed that about % of patients with a very severe metabolic acidosis survived to icu discharge with a good neurological recovery. introduction: precarious socio-economic status can directly influence health, need for hospitalisation and mortality, according to a previous study performed in european countries. similar findings have been reported from anglo-saxon countries in the setting of intensive care. due to the different structure of the healthcare system in france, we aimed to investigate whether socio-economic status influences initial severity of disease and months mortality in patients admitted to intensive care in france. patients and methods: prospective, multicentre, cohort study including adult patients admitted to one of participating intensive care units (icus) between and , and presenting failure of one or more major organs. patients were considered to have a precarious socio-economic status if they presented at least one criterion of social vulnerability or a high epices deprivation score. results: data on social vulnerability were available for patients, of whom . % were considered to be socially vulnerable. compared to non-vulnerable patients, socially vulnerable patients were younger ( . vs . years, p = . ), more frequently had chronic disease ( . vs . %, p = . respectively for congestive heart failure and . %vs . %, p = . for chronic respiratory disease), had higher levels of physical dependency ( . vs . %, p = . ), and were more often classed as having long-term health conditions ( . vs . %, p < . ). conversely, non-vulnerable patients had greater severity of disease at admission to the icu than those classed as vulnerable, both in terms of saps ii and sofa scores (respectively . vs . (p = . ) and . vs . (p = . )). findings were similar after adjusting for major confounders (adjusted odds ratio (or) . , % confidence interval (ci) [ . - . ], p = . ). mortality at months was not significantly different between socially vulnerable patients and those not considered vulnerable, respectively . vs . % (p = . ), even after adjustment for initial severity. conclusion: despite less severe disease at admission to the icu among patients considered socially vulnerable, -month mortality did not differ significantly between those who were socially vulnerable and those who were not. these findings suggest that the french healthcare system provides good protection for the most disadvantaged members of society, particularly when they are admitted to the icu. introduction: an approach of the quality of care may involve assessing the patients' satisfaction. however, the extended caregiverpatient and family relationship, specific to the critically ill patients, may also require to assess the proxies' satisfaction. the opinionfamily tool was developed to assess the satisfaction of the critically ill patients' proxies, in an anonymous and continuous fashion. we conducted a study in the icu of tenon hospital (paris, france) between mars and august . the opinion-family questionnaire, built with categories ( items each), aimed to measure the proxies' satisfaction regarding their perception of the quality of care. all the proxies were invited to express voluntarily and anonymously his her degree of agreement as a response to a statement by the selection of the corresponding stars (strongly disagree- star, disagree- stars, neither agree nor disagree- stars, agree- stars, strongly agree- stars) using a secure touch screen disposed in the waiting room of the icu. results: altogether, patients were hospitalised during the study period, and proxies completed the questionnaire. all the responders spoke french. only responders ( %) answered more than one time. of the responders, ( %) were the referring person, ( %) were children and ( %) were spouses. during the study period, ( %), ( %), and ( %) responders had visited their relative to times, to times, and more than times, respectively. the different categories assessed by the opinionfamily tool were related to «the family and the patient» (fig. a) , «the family and the environment» (fig. b) , and «the family and the caregivers-availability, trust, support, and information» (fig. c) . the corresponding levels of satisfaction (responses of at least stars) were respectively , , , , , and %. some items were associated with a poor satisfaction (participation to the care, identification and availability of the caregivers). conclusion: the implementation of the opinionfamily tool allowed a continuous evaluation of the satisfaction of the critically ill patients' proxies. a systematic implementation of this tool in the icus may be useful to the caregivers for a better understanding of the needs of the proxies. in addition, this tool may allow rapid changes in icu organizations and behaviours to improve the proxies' satisfaction, which may ultimately, improve the care of patients. many factors influence end-of-life decisions (eol). we describe eol decisions in patients with acute respiratory failure and their impact on patients' prognosis. patients and methods: an international observational study included all patients with acute respiratory distress over a -month period. icu in countries were involved. demographic, clinical and biological data were compared between patients with and without decision of lst limitation. we also compared surviving patients after lst limitation decision to those who eventually died. results: among the patients, mortality was . %. a decision of lst limitation was reported in patients ( . %). in univariate analysis, patients with lst limitation decision were older and more frequently hospitalized for a medical condition, had a lower body weight, a higher sofa score, and presented active neoplasia immunosuppression or chronic liver failure more frequently (p < . for all). patients admitted after trauma, drug overdose or pulmonary contusion were less subject to have an lst limitation decision (p < . ). in contrast, patients with non-cardiogenic shock were more subject to these decisions (p = . ). eol decisions were less frequent in lower-middle income countries as compared to high and middle-high income countries (p < . ). multivariate analysis will be presented. among patients with an lst limitation decision, survived ( . %). mortality was higher in this group than in the whole study population (p = . ). in univariate analysis, death after decision of lst limitation was associated with admission for a medical condition (p = . ), severe ards, higher inspiratory pressure, non-cardiogenic shock, higher sofa score with or without respiratory component and chronic liver failure (p < = . for all). on the contrary, admission for trauma was associated with survival (p = . ). regarding the patients who died during their hospital stay, did not receive a decision of lst limitation ( . %). decision of lst limitation was more frequent in older patients (p < . ) and in high-income countries. conclusion: decisions of lst limitation are frequent in the icu, and are associated with increased age and medical severity. however, a significant percentage of these patients survived. interestingly, almost half of the patients who eventually died during their hospital stay had not been subject of a decision of lst limitation. evaluation of the decision-making process leading to a decision not to readmit a patient to the intensive care unit during a same hospital stay introduction: the risk-benefit ratio of (re-)admission to the intensive care unit (icu) has been widely discussed in the literature. however, the ethics of non-readmission during a single hospital stay have not been widely addressed. a decision not to re-admit a patient to the icu could be seen as a limitation of therapy, thus falling within the scope of the law dated april , by denying the patient access to potentially-available healthcare resources. in this context, we aimed to-( ) investigate whether decisions not to re-admit patients to the icu are taken in accordance with french legislation + and ( ) identify the characteristics of patients concerned by this type of decision. patients and methods: this study was based on data from the prospective, multicentre ivoire cohort (influence of socio-economic vulnerability on initial severity and prognosis of patients admitted to the icu + phrc-ir ). we identified patients included in two large regional university hospitals in the east of france for whom a decision not to re-admit was taken during a single hospital stay. the decisionmaking process was evaluated based on a questionnaire comprising items developed by a sociologist from semi-directive interviews with clinicians. results: among patients discharged from the icu alive, a decision not to re-admit to the icu during a same hospital stay was noted in the medical file of patients ( . %). this decision was primarily made on the day of discharge ( . %), and those involved in the decision included-the family, an outside consultant, and the patient themselves in , . and . % of cases respectively. the decision was justified in medical terms in . % of cases, and the main reasons cited were-( ) therapeutic impasse ( . %) + ( ) comorbidities ( . %) + ( ) degree of dependence of the patient ( . %). patients concerned by decisions of this type were generally older ( vs . years, p < . ), with more comorbidities (median vs , p = . ), greater loss of dependence according to katz's activities of daily living ( vs , p < . ), and longer duration of life-sustaining therapies ( . vs days, p = . ). conclusion: although the profile of the patients identified in this study likely justified the decision not to re-admit the patient to the icu, there is room for improvement in the decision-making process. introduction: most of organ donors are brain dead patients. in some cases, patients are identified as potential donors before brain death and will undergo intubation and mechanical ventilation for the sole purpose of awaiting brain death. the aim of this study is to evaluate the practices of professionals in charge of potential donors. (table ). in this case, the issue of organ donation was addressed to the relatives before intubation by % of icup and % of non icup (p = . ). % of participants never addressed organ donation before the brain death. for the % who have done so at least once, organ harvesting never happened in % of cases. legitimacy and difficulties ( table )- % of respondents felt that when a decision of treatment withdrawal or withholding is taken, the patient should not go to icu for any reason and % think that these patients should be allowed to die "quietly". the prospect of an extubation if brain death does not occur or in case of organ donation refusal is a problem for % of icup and % of non icup (p = . ). % of icup and % of non icup think they would need to receive training. conclusion: this study shows that pursuing mechanical ventilation for the sole purpose of awaiting brain death and organ harvesting is a common practice, and that intubating a patient for this purpose alone is done in most of cases but could still be more generalized. on the other hand, information to the relatives should be improved. - . ] . the effect of pp on the monitored parameters varies significantly between each patient but also between each session for the same patient. in positive responders, the effect continues statistically for to h depending on the parameter studied- . h for vd vt, . for phase slope, for petco and for cdyn. the maximum effect of prone positioning on selected parameters seems to be obtained after h of therapy. the acute respiratory distress syndrome (ards) is characterized by lung infiltration with activated neutrophils. neutrophil extracellular traps (nets) are antimicrobial structures released by neutrophils. nets have also been associated with tissue damage in experimental models of acute lung injury. whether nets are involved in the pathogenesis of human ards and could be a potential therapeutic target is unknown. we aimed to quantify alveolar nets production in patients with pneumonia and ards and assess its relationship with outcomes. patients and methods: prospective monocentric study. patients admitted in the icu in with pneumonia and moderate severe ards were included. immunosuppressed patients were excluded. nets (dnamyeloperoxidase) levels were measured by elisa in broncho-alveolar lavage (bal) fluid and serum samples of ards patients and in those of control patients (n = ). patients with higher and lower bal fluid nets levels were compared using the median as a cutoff value. results: thirty-five patients with bacterial (n = ), viral (n = ) or non-microbiologically documented (n = ) pneumonia and ards were included. nets levels were significantly higher in bal fluid than in blood of ards but not of control patients (fig. introduction: the ratio of arterial oxygen partial pressure to fractional inspired oxygen (pao fio or p f) is daily used to assess patients' evolution under ventilatory support. some studies reported the reliability of percutaneous oxygen saturation (spo ) to appreciate pao easy to get on bedside. thus two equations have been proposed-rice equation and ellis equation. however, no large prospective study assessed the reliability of such equations to estimate the p f at the bedside in real conditions. using the spectrum (severe hypoxemia-preva-lence, treatment and outcome) study, we aimed to evaluate the reliability of spo obtained by rice and ellis equation. this study is a planned companion of spec-trum study, a recent prevalence-point-day conducted by the srlf trial group in french-speaking icu aiming to report the patterns and outcomes of hypoxemic patients (defined by p f < mmhg). we included in the analysis all patients under mechanical ventilation with spo < % (according to limit of the rice study). spo and fio were measured simultaneously to arterial blood gas were drawn. results: among patients of the spectrum study, were on mechanical ventilation and had undergone arterial blood gas with simultaneously recorded spo and fio . of note, p f was < mmhg for + between and for + and between and for . pairwise correlations of truth p f with estimated p f was good (rice-spearman's rho = . , p < . -ellis-rho = . p < . ). bland-altmann test showed an important variability of results (p f vs rice (figure) - . ± . -p f vs ellis- . ± . ). the variability decreased with lower p f. caution may be used to interpret our results because we did not reported the quality of spo signal at the bedside. conclusion: regarding the variability of the results, whatever the used equation, caution may be used to predict the p f by the spo fio ratio in patients under mechanical ventilation. introduction: morbid obesity and ards both affect respiratory mechanics mainly through their respective impacts on chest wall and lung elastances. we present a unique series of patients combining very severe morbid obesity and moderate to severe acute respiratory distress syndrome (ards). we describe the use of trans-pulmonary pressures (tpp) measurements for optimization of external peep setting. patients and methods: the monocentric observational study was performed in morbidly obese patients admitted for moderate to severe ards. we performed an incremental peep trial ( cm h o steps) with tpp measurement (nutrivent probe, sidam, italy) in a semirecumbent position as previously described. a decremental peep trial after a recruitment maneuver was not performed since the safety of such a maneuver in this specific population is largely unknown. we defined two ways for determination of external peep setting-( ) peep necessary to obtain a positive expiratory tpp and ( ) peep necessary to obtain a plateau pressure between and cm h o (maximal alveolar recruitment express strategy). data are expressed as numbers (%) and medians (interquartile range). statistical analysis was made using the xlstat software. results: we enrolled during years morbidly obese patients (bmi (ir - )) admitted for a moderate to severe ards. clinical characteristics are displayed in table . the express strategy indicated a peep setting of cm h o (ir - ) whereas tpp-guided peep was cm h o (ir - ), p = . . driving pressure was higher in the express strategy peep setting ( . cm h (ir - )) than in the tpp-guided peep ( . cm h (ir . - )), p = . . tpp-guided peep setting was higher than indicated by the express strategy in all but one patient. one patient suffered from transient hypotension when external peep was set at cm h o, while no patient displayed an inspiratory tpp higher than cm h o. additional data will be provided during the meeting-pressure-volume curve at zeep ( patients), crf measurements ( patients) and abg and capnometry values at each peep level ( patients) . in our ards patients with extremely severe obesity, an incremental peep trial with tpp measurements appeared to be safe and indicated a peep setting significantly higher than for the commonly-used ards strategies. such an approach deserves further comparisons with other modalities of monitoring, such as crf measurements, eit studies, etc. severe poisoning by cardiotoxic drugs and circulatory assistance: -year experience at french university hospital tardif elsa , conil jean-marie , georges bernard , marcheix bertrand , crognier laure , bounes fanny , delmas clement chu rangueil, toulouse, france correspondence: tardif elsa -tardif.elsa@gmail.com annals of intensive care , (suppl ):f- introduction: toxicity from cardiac drugs is associated with a large number of fatalities, significant morbidity and healthcare consequences. severity of these poisonings can be explained by a refractory cardiogenic shock not responding to optimal conventional treatment. criteria of circulatory assistance indications remain unclear. the aim of the study was to describe and to compare patients intoxicated by cardiotoxic drug treated with or without veno-arterial extracorporeal membrane oxygenation (va ecmo). patients and methods: retrospective cohort study conducted at french university hospital. all patients intoxicated with cardiotoxic drugs between january and march were included. patients were divided into groups-with and without va ecmo. results: among the patients included in the study, patients were treated with va ecmo ( %) and patients with conventional therapies. ecmo was respectively employed for refractory shock and cardiac arrest in and cases, all patient required vasopressor support. in-hospital mortality was . % and was significantly higher in the ecmo group ( . %). beta-blockers with membrane stabilizing activity and non-dihydropyridine calcium channel blockers poisoning were the most commonly reported in the ecmo group. mean time from hospital admission to initiation of ecmo was h and the average ecmo duration was . days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . no serious adverse reaction was reported during this period. results expressed in median value ± confidence interval conclusion: refractory cardiogenic shock following cardiotoxic drug poisoning requiring circulatory assistance is associated with significant mortality. even if its use seems justified by the literature, the implantation criteria must be specified and this after an optimal conventional treatment to prevent multiple organ failure. the cdv of patients in the edass group was significantly higher (p < . ) at all-time points after the introduction of catecholamines than among those without edass, as early as h from catecholamine initiation (fig. ) . a strategy in two steps (cdv > µg kg at h and or cdv > µg kg at h) was able to predict edass with sensitivity of %, specificity %, positive predictive value % and negative predictive value %. overall, this two-step strategy identified high-risk patients at h, of whom presented edass. conclusion: overall, our results confirm that early death directly attributable to septic shock could be effectively predicted by the cdv in the first hours of treatment. these results will help to select patients eligible for innovative therapies aimed at improving early mortality in septic shock. introduction: in patients with cardiac arrest, end-tidal co (etco ) has been proposed to monitor the efficacy of cardiopulmonary resuscitation (cpr) but uncertainty persists on its interpretation. we hypothesized that exhaled co may also by affected by occurrence of "lung airways" collapse previously noticed during cpr. because this closure may possibly also limit oxygenation + analysis of the entire exhaled co time waveform-may give information of high clinical value to manage cpr. we report preliminary results from a clinical and bench study aimed at describing the pattern of the capnogram during cpr. induces a systemic inflammatory response associated with an immune dysregulation and a significant pulmonary dysfunction which has been well characterized. surprisingly, there are only a few data available on immunological changes induced by ecls. we believe that ecls leads to immune dysfunction that could expose patients to nosocomial infections. patients and methods: a two-phase study was lead. first we analyzed blood cell count with differential (including lymphocyte, neutrophils and monocyte counts) in all patients who received ecls in our institution from to within the first week following ecls initiation. secondly, monocytes, granulocytes, dendritic cells and lymphocytes function were assessed at day , day and day using flow cytometry and functional tests in patients receiving ecls and compared to patients with cardiogenic shock without ecls. results: among patients with elcs we found an early and persistent lymphopenia and a late neutrophilia (found to be associated with poor outcome in critically ill patients). compared to control (n = ), we found in patients who received ecls (n = ) a significant increase in immature granulocytes ( . ± . on day one versus . ± ± , p = . ) and lymphocytes apoptosis. ecls induced changes in myeloid derived suppressors cells proportion ( . % ± . on day three versus . % ± . before ecls, p = . ), which has been recently associated with a higher incidence of nosocomial infections and seems to be major actors of sepsis-induced immune suppression. complement component a receptor (c ar) from the neutrophil cell surface, was also decreased after ecls initiation (ratio of mean fluorescence index . ± . on day one, p = . ) which is a sign of complement-induced neutrophil dysfunction in septic patients. conclusion: ecls induces quantitative and qualitative leukocytes dysfunctions that can lead to a greater susceptibility to nosocomial infections which contribute to the poor outcome observed in several studies. introduction: aspiration pneumonia is a common complication of cardiac arrest. although its real incidence remains undetermined, probabilist antibiotherapy is frequently or even systematically prescribed in these cases. we assessed the incidence of out-of-hospital cardiac arrest-related aspiration pneumonia and the impact of a microbiological documentation in regard to antibiotherapy course. patients and methods: all patients admitted for out-of-hospital cardiac arrest from to were studied. in our icu, aspiration pneumonia is suspected when a clinical syndrome (fever, per resuscitation constatation) and or chest radiography infiltrates were present. in case of suspected aspiration pneumonia, a microbiological documentation was performed before initiation of probabilist treatment with amoxicillin-clavulanate. we retrospectively defined if patients have aspiration pneumonia using the following criteria-per resuscitation constatation, chest radiography infiltrates, fever. the number of microbiological documentation leading to an antibiotherapy modification was recorded as well as pathogens types. data are expressed as numbers (%) and medians (interquartile range). statistical analysis was made as appropriate using the xlstat software. results: patients were studied. clinical characteristics are displayed in table . ( ) received a probabilist antibiotherapy and ( ) were retrospectively considered with aspiration pneumonitia. results of microbiological documentation were ( ) positive microbiological sample and ( ) with a positive threshold whose ( ) were considered colonized (i.e. no clinico-radiological sign). on the entire positive culture sample, ( ) were positive with oropharyngeal flora as unique pathogen, ( ) introduction: this study aimed to assess whether augmented renal clearance (arc) impacts negatively on piperacillin-tazobactam pharmacokinetic pharmacodynamics (pk pd) target attainment in critically ill patients receiving g day by continuous infusion. patients and methods: over an -month period, all critically ill patients treated by piperacillin-tazobactam for a suspected or documented sepsis without renal impairment were eligible. during the first three days of antimicrobial therapy, every patient underwent -hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at steady state. the main pk pd outcome investigated in this study was the rate of empirical target non-attainment using a theoretical target mic of mg l − for piperacillin and mg l − for tazobactam. the secondary clinical outcome was the rate of therapeutic failure in microbiologically documented infections, defined as an impaired clinical response with a need for escalating antibiotics during treatment and or within days after end-of-treatment. over the study period, patients were included in the primary pharmacological analysis and in the secondary clinical analysis. using a mic of mg l − for piperacillin, the rate of empirical target non-attainment in the overall population was %, with a strong association with crcl ( fig. introduction: invasive fungal infections are a major burden in solid organ transplantation, especially in patients receiving liver graft. however, their incidence has decreased thanks to the development of an antifungal prophylaxis in the post-transplantation period. in patients at high risk of invasive fungal infection (ifi), this strategy is recommended, whereas its benefit remains controversial in low-risk patients. however, there is no clear definition of these two patients groups. our aim was to provide recent data on epidemiology, mortality and ifi risk factors in the early post-operative course in a population without any antifungal prophylaxis. results: the number of beta-lactam antibiotics was . of these requests, half were for piperacillin ( . %), and onethird were for amoxicillin ( . %). the other dosages were mainly for cloxacillin, cefepime, cefotaxime and ceftriaxone. the results confirmed that serum concentrations of piperacillin ( . ± . vs . ± . mg l − < . ) and amoxicillin ( . ± . vs ± mg l − < . ) significantly were higher in patients with neurological disorders or wakefulness delays. the roc curves allowed the predictive values associated with the presence of neurological disorders attributable to antibiotic treatment, corresponding to residual serum concentrations of piperacillin of mg l − and amoxicillin of mg l − . a predictive value for neurological disorders of these concentrations is proposed for residual serum concentrations greater than mg l − for both antibiotics ( % specificity and sensitivity). conclusion: our results suggest that there is an association between a residual concentration of piperacillin and amoxicillin greater than mg l − and the occurrence of neurological disorders. pharmacological therapeutic monitoring of beta-lactams in critically ill patients may be a useful intervention to optimize the antibiotic regimens and to avoid antibiotic-related toxicities. ( ) ( ) ( ) ( ) ( ) . patients with a gnb-bsi were included and were divided into two groups according to the resistance (r) profile (bsi due to a r isolate or not). the following resistances were considered-all gnb-bsi including pseudomonas spp., acinetobacter spp., stenotrophomonas spp. and enterobacteriacae (eb) for which the following antimicrobial resistances were considered-ticarcillin and ceftazidime (cefta) (pseudomonas (pa)), third generation cephalosporin ( gc) (eb) and imipenem (all gnb). after variable selection using random forest and univariable mixed logistic regression models, a multivariable analyses using a mixed model with a random effect (center). sub-group analyses were performed according to species (pa and eb) and resistance for eb. results: from , patients admitted in an annual median of french icus, experienced an icu-acquired (> h.) bsi, ( %) bsi due to gnb, including ( %) bsi due to r isolates. pa was identified in ( %) (mdr-pa bsis ( %)) and eb in ( %) (mdr-eb bsis ( ( %)). the raw mortality rate was % in the overall population and % in the patient with gnb bsi. it was significantly higher for r gnb bsi ( vs % for susceptible gnb bsi, p < . ). after adequate adjustment in a multivariate analysis, we showed that r-gnb bsi was significantly associated with mortality compared to susceptible strains (fig. ) . by considering species subgroup, the effect was not significant for resistant pseudomonas aeruginosa (p = . ) but remained significant when considering only eb. considering eb resistance, the impact of gc r showed a trend to an increased mortality risk whatever there was no effect of imi r (n = ( %)) on prognosis. limitation-the absence of information about antibiotic consumption may partly explain the remaining significant center random effect in the final models. conclusion: in a large french database, after adequate adjustment on prognostic factors, resistant bgn-bsi was associated with a higher icu mortality than susceptible one. the effect was mainly due to eb gc r. severely injured group versus . ± . days for the non-severely injured patients (p < . ). in multivariate analysis, heart rate (> min) and vittel score (≥ criterias) were related to the probability of belonging to the severely injured group (p = . ). the -hour mortality rate was . % in the ed and the -day mortality rate was . %. the development of a network in the ed hosting non vital polytraumas remains crucial. its primary goal will be to meet technical and time requirements and establish in-hospital triage algorithms based on clinical variables, in order to detect these patients at an early stage and offer them priority care in our overcrowded eds. introduction: the trauma of traffic accidents and particularly cranial trauma are, due to their frequency and severe consequences in both the short and long term, a real public health scourge on a global scale. studies of the epidemiology of cranial trauma by traffic accidents and their prognosis are rare at least in underdeveloped or developing countries. in addition, the impact of extracranial lesions on cranial trauma prognosis has long been discussed. the purposes of our study were to examine the epidemiological aspects and to determine the factors correlated to the immediate and distant prognosis of isolated cranial trauma. patients and methods: retrospective cohort spread over years (from to ) and including patients with isolated cranial trauma by traffic accidents (mean age . years, sex ratio- ). we proposed to study the factors correlated with a poor prognosis in terms of death in hospital and glasgow outcome scale (gos) at months unfavorable in dual analysis (univariate and then multivariate). for the gos study, patients were divided into groups-gos favorable for patients with good recovery (gos = ), recovery with a light handicap (gos = ), gos unfavorable for those having survived with a severe disability (gos = ), a vegetative or pauci-relational state (gos = ) and those who died (gos class ). results: hospital mortality was % and the gos at months was distributed as follows: death ( . %), vegetative state ( . %), severe disability ( . %), mild disability ( %) and good recovery ( . %). the -month gos was deemed unfavorable in . % of the cases. various after effects were observed in survivors: physical ( %) dominated by headache ( . %), sleep disorders ( . %) and epilepsy ( . %); memory disorders ( . %) or concentration ( . %) and finally emotional after effects ( . %) with irritability ( . %) and aggressiveness ( . %). in multivariate statistical analysis, independent predictors of mortality were arterial hypotension, hypoxia extradural hematoma (edh),, acute subdural hematomas (sdh), diffuse axonal injury and ventilator associated pneumonia. those correlated with an unfavorable gos were an age ≥ years, hypotension, cerebral edema, coma duration ≥ . days, edh and h glucose ≥ . mmol/l. conclusion: although the short-term prognosis of head trauma seems to be improved at present, the long-term consequences of cranial trauma remain fairly frequent, and often underestimated, which underlines the importance of their screening and their proper care. the average age of the survivors ( . ± . years) was lower than the mean age of the deceased ( . ± . ). ra was the cause of the trauma in % of the cases followed by the fall found cat % of the patients. prehospital care only concerned % of patients. the univariate analysis showed that the main factors of occurrence of death were age (p = . ), glasgow score (p = . ) anisocoria (p = . ), shock (p = . ) % of deaths were due to intracranial hypertension, haemorrhagic shock in % of patients and ards in % of polytrauma patients. conclusion: the management of polytrauma can not be improvised. the medical teams must be coordinated by an emergency physician in prehospital, a doctor anesthesiologist-resuscitator at the reception. some systematic gestures such as preparation of the reception allow to optimize the management of the time. introduction: benign cranial trauma is a major public health problem due to both its frequency and the health costs it creates. the aim of this study was to identify relevant clinical factors that could predict the achievement of brain ct and situations at risk for neurosurgical care and for which ct was a necessity. patients and methods: this is a month prospective study, including patients with benign traumatic brain injury (glasgow coma score gcs ≥ ), patients under years of age and patients with gcs < were excluded. epidemiological, clinical, paraclinical, therapeutic and evolutionary parameters were studied. a multivariate and univariate statistical study was carried out to reveal the predictive factors of a ct anomaly and the predictive factors for the neurosurgical care. data were entered and analyzed using spss . and excel software. results: the average age of patients was years with a predominance of male, and sex ratio of . . the cause of the btb was mainly represented by the accidents of the public road in . % of the cases. . % of the patients were asymptomatic, the most common symptomatology was dominated by the initial loss of consciousness ( . %), headache ( . %). the glasgow coma score was distributed as follows-gcs ( . %), gcs ( . %) and ( . %). . % of patients had clinical signs of trauma to the skulland or face. brain ct was performed in . % of patients, and . % had abnormal ct. the use of neurosurgical care was of the order of . %. in univariate analysis-the predictive factors for a ct abnormality were the intoxication during the brain trauma, the gcs < , signs of trauma in the skull face, the vomiting, the initial loss of consciousness, the comitial crisis and the predictive factors of neurosurgical care were the gcs < , the anisocoria, headache, the vomiting, the amnesia, the initial loss of consciousness, the comitial crisis, the anormal ct, the extradural hematoma or the subdural hematomat in multivariate analysis-the predictive factors for a ct abnormality were the gcs < , the initial loss of consciousness and the predictive factors for the use of neurosurgical care were the gcs < , signs of trauma in the skull face, the amnesia, the comitial crisis, the hsd. conclusion: an algorithm must be applied in collaboration between resuscitators and neurosurgeons to improve the quality of benign cranial trauma management. prognostic value of hyperchloremia in patients with traumatic brain injury: a prospective observational study taghouti introduction: background-traumatic brain injuries (tbi) are a major public health problem. they are the leading cause of death among those aged less than years. hyperchloremia is a common electrolyte disturbance in patients with tbi. hyperchloremia has been associated with increased morbidity and mortality in critically ill patients + however, its prognostic significance in tbi patients is poorly documented. the aim of this study is to describe the prevalence and outcomes of hyperchloremia in patients with tbi admitted to the intensive care unit. patients and methods: in a prospective design, we included consecutive patients with tbi ( males + median age- years) admitted to the icu in charles nicolle hospital of tunis from mars to september . adult patients (aged ≥ years) with isolated tbi or associated with minor extra-cranial injuries (defined as all non-head abbreviated injury scale < ) were included. hyperchloremia was defined as a chloride level > meg/l. clinical and laboratory variables were compared between survivors (n = ) and non-survivors (n = ). we assessed the association between hyperchloremia -h post-admission and -day mortality. p < . was taken to indicate statistical significance. results: the median sofa score at t was points and the median igs score was points. the median iss was points. there were cases of mild head injury, moderate head injury and severe head injury. the -day mortality was %. hyperchloremia occurred in patients ( %) and the incidence was significantly different between survivors and non-survivors ( vs. %, respectively, p < . ). in addition to hyperchloremia (p = . ), other laboratory variables were associated with -day mortality-hypernatremia (p = . ) and hypoalbuminemia (p = . ). conclusion: hyperchloremia -h post-admission was associated with -day mortality in patients with tbi. this index could be useful prognostic marker. efforts should focus on the prevention of hypernatremia and hyperchloremia in this vulnerable group of critically ill patients. child traumatic brain injury naili amine blida rp, algÉrie correspondence: naili amine -drnailiamine@yahoo.fr annals of intensive care , (suppl ):p- introduction: brain injury in children is common and mild in most cases, but it remains the leading cause of death and disability in children over year of age worldwide. the peculiarity of the child is that he possesses not mature brain and that the consequences of injuries acquired by traumatic brain injury can lead to the loss of capacities, as well as the non-acquisition of function, but above all the risk impact on learning abilities. the objective of the study is to define the incidence rate of cranial trauma in children as well as the mortality and morbidity of this scourge which presents a major public health problem. patients and methods: it is a descriptive retrospective study of a series of children hospitalized in neuro-resuscitation service during the period january to december , , including children admitted for cranial trauma. clinical, para-clinical, etiological and therapeutic data were collected from hospitalization records. results: in a series of children hospitalized during the defined period, children were admitted for cranial trauma, i.e. a frequency of %. the average age was years [ h of life- years], with a sex ration of among the children, had severe head trauma, a rate of % + whose causes are variable- road accidents, domestic accidents, traffic accidents, and obstetric accident, admitted with a pediatric glasgow score between and , and all required mechanical ventilation of the head trauma, were operated for different lesions- extra-dural hematomas, cranio-cerebral wounds, subdural hematomas, decompressive craniectomy, and embarrure. children had died following severe head trauma, i.e. a mortality rate of %, the morbidity rate of head trauma in the tipaza wilaya was . , children year, the average length of stay in intensive care units was days, with several complications of decubitus, and functional due to the primary and secondary lesions of the cranial trauma. the head trauma of the child is a public health problem, its functional prognosis can be dramatic when it is severe, its management must be early and multidisciplinary. introduction: the aim of the study was to identify factors predicting lung contusion in trauma children. patients and methods: retrospective study conducted for a period of years (january , -december , ) in a medical surgical intensive care unit. all trauma patients younger than years were included. two groups were compared-those with lung contusions (c + group) and those without lung contusions (c − group). results: we included patients. the mean (sd) age was . ( . ) years. chest injury was diagnosed in patients ( . %). all our patients needed mechanical ventilation. lung contusions were diagnosed in patients ( % of all patients and . % of patients with chest trauma). in multivariate analysis, independent factors predicting lung contusion were road traffic accident (odds ratio [or], . + % confidence interval [ci], . - . + p = . ), increased pediatric risk of mortality (prism) score (or, . + % ci . - . + p = . ), hepatic contusion (or . + % ci . - . + p = . ), and pelvic ring fracture (or, . + % ci . - . + p = . ). death occurred in patients ( . %). intensive care unit mortality was significantly higher in the c + group (or, . + % ci . - . + p = . ). however, mortality was not differentbetween the groups after adjusting for prism score (or, . + % ci . - . + p = . ) or after adjusting for injury severity score (or, . + % ci . - . + p = . ). conclusion: lung contusion is common in critically ill children with chest trauma. the diagnosis should be considered in patientswith road traffic accident, increased prism score, hepatic contusion, and pelvic ring fracture. introduction: chest trauma is often associated with pleural effusion (hemothorax and or pneumothorax). drainage of the pleural space by a chest tube is a common intervention in such situations. blunt dissection technique with a kelly clamp is preferred to classical trocar techniques to prevent severe complications, like perforation of thoracic or abdominal organs. despite these precautions, malposition remains the most common complication of tube thoracostomy. we investigated a new technique of bougie-assisted chest tube insertion to prevent chest tube malposition after chest drainage of post traumatic pleural effusion. patients and methods: we performed a controlled before-and-after study to assess the ability of a bougie-assisted chest tube insertion technique, compared to a standard blunt dissection technique, to prevent chest tube malposition. for the bougie-assisted group, we used a disposable eschmann-style bougie, commonly used to guide the endotracheal tube during difficult intubations. technique consisted in blunt dissection until the parietal pleura is opened. thoracostomy tube was preloaded onto the bougie and bougie was advanced alongside the finger, with apical or caudal direction after entering the chest cavity, depending on the type of pleural effusion. thoracostomy tube was then advanced forward utilizing a seldinger technique. the primary end point was optimal position of the chest tube. the tube position was blindly assessed on standard chest x-ray. in pneumothorax, optimal position was apical (above the aortic arch), and in hemothorax or mixed-effusion it was basal ( cm above the diaphragm or lower). results: a total of patients were enrolled (bougie-assistedn = + conventional-n = ). chest tubes were optimally position in ( %) in bougie-assisted group and ( %) in conventional group, or . , ic % = [ . - . ], p < . . efficacy of chest drainage (defined on chest x-ray as the absence of visible pleural line for pneumothorax and as a clear costophrenic angle for hemothorax) was assessed in ( %) in bougie-assisted group and in ( %) in conventional group, or . , ic % = [ . - . ], p < . . average procedure time was s ( % ci - s) for bougieassisted group and s ( % ci - s) for conventional group, p < . . no severe complication was observed in both groups. conclusion: bougie-assisted chest tube insertion technique prevents chest tube malposition, is safe, effective and shortens procedure time for the post traumatic pleural effusion drainage. introduction: infectious complications determine the prognosis of burned patients. however, the emergence of bacterial resistance to antibiotics threatens treatment efficacy, which is due to an inadequate antibiotic consumption inqualitative and quantitative terms. the objective of this study was to describe the profil of consumptionand susceptibility to antibiotics. and, to explore the predictive factors for theemergence of mrb in the service of burns and plastic surgery. patients and methods: it is a retrospective study including severe burnedpatients hospitalized for years in the plastic surgery department of theuniversity hospital ibn rochd from january to december . bacterialecology was described, and the distribution of the seeds by group, by species andby period of time was detailed. the ddd jh (daily defined dosage reportedin days of hospitalization) was used to assess the consumption of antibiotics. p correlation coefficients were calculated to explore the association betweenconsumption of antibiotics and the emergence of the bmr (multiresistantbacteria), and identified predictors of this emergence. results: on samples taken, bacterial and fungal strains were identified, with a predominance of p. aeruginosa ( . %), a. baumani i ( %) and s. aureu s ( %), the number of strains increased with the duration of the stay reaching itsmaximum from days in hospital. the ceftazidine ( . ddd dh), imipenem ( . ddd dh), and amikacin ( . ddd dh) were themost used antibiotics during our study, also + the profile of consumption increasedbetween and . bmr were isolated + the eblse were at the top ( . %) follow up of thecrpa ( . %), followed by the irpa ( . %) follow-up of the crab ( . %) then the irab ( . %) and finally the mrsa with a portion of . %. the profile of bacterial resistance has varied significantly for severalantibiotics bacteria pairs. conclusion: it remains difficult to show correlations between antibioticconsumption and bacterial resistance. however, these data are particularly usefulin the epidemiological surveillance of bacteria to better guide probabilisticantibiotic therapy. introduction: eclampsia is a rare but serious threat to maternal and fetal well-being. the aim of this study was to assess the incidence of eclampsia and its morbidity and mortality. patients and methods: we conducted a retrospective survey in a third level tunisian university teaching hospital from january to december . we included all patients with the diagnosis of eclampsia. results: in study period deliveries were registered. women with eclampsia were identified hence the incidence of eclampsia was . per deliveries. the median gestational age at the time of eclampsia was weeks. no maternal deaths due to eclampsia were recorded. the delivery mode was caesarean section in % of eclamptic patients. the recurrence of eclampsia despite magnesium sulfate prevention was observed in % of patients. severe complications of eclampsia were recorded in . % of patients- posterior reversible encephalopathy syndrome, acute pulmonary edema, and hellp syndrome. . % of new born were preterm. there were stillbirths and neonatal deaths. conclusion: the incidence of eclampsia was very high probably due to center effect. it's essential to raise awareness among mothers in the community regarding early signs and symptoms of preeclampsia eclampsia and to design a better tracking system for antenatal care program. introduction: to monitor maternal mortality which is an indicator of the quality of obstetrical care and anesthesia resuscitation, our country worked to set up several programs targeting maternal and child health. the aim of this work was-to evaluate the maternal mortality rate in our department and its evolution. to identify the cause of death and classify it depending on whether it is preventable or not. to spot the deficiencies either in the care management or the organization of the care system. to propose ways to improve our care and to fill the failures. patients and methods: it was a retrospective study about maternal death, performed at the department of gynecology and obstetrics, over a -year period (from to ) , that have reported cases of maternal death according to the world health organization definition. results: the maternal mortality rate (mmr) was . for every , live births. the average age of our patients was . years. the main risk factors for maternal mortality are unfavorable socioeconomic conditions, high-risk pregnancies, multiparity, primiparity and a poor follow-up of the pregnancy. the main causes of maternal death are represented by direct obstetric causes ( %) allocated as followspostpartum hemorrhage ( %), pregnancy toxemia ( %), acute fat hepatic steatosis ( %), infection ( %) and complications of anesthesia ( %). indirect obstetric causes were found in % of deaths. death was considered avoidable in . % of cases. conclusion: at the end of this work, we were able to pull several recommendations in order to reduce m.m.r. health education. facilitate access to care for the parturient, improve care and conditions of childbirth. continuous training of the medical and paramedical staff. introduction: mechanical ventilation can help improve the prognosis of sepsis. while adequate delivery of oxygen to tissue is crucial, hyperoxemia may be deleterious. invasive out-of-hospital ventilation is often promptly performed in life-threatening emergencies. we propose to determine whether the arterial oxygen pressure (pao ) at intensive care unit (icu) admission affects mortality at day (d ) in patients with septic shock subjected to mechanical out-of-hospital ventilation. patients and methods: we performed a monocentric retrospective observational study on patients with septic shock admitted to the icu. pao was measured at icu admission in patients subjected to invasive ventilation before any hospital admission. the primary outcome was mortality at day (d ). results: forty-nine ( %) patients with septic shock were mechanically ventilated before any hospital admission and transferred to the icu. the mean pao at icu admission was ± and ± mmhg for alive and deceased patients at d , respectively. pao was significantly associated with mortality at d (p = . ). using a roc curve, the corresponding auc was . [ . - . ]. for a pao > mmhg, the or for mortality at d was . [ . - . ] (p = . ), whereas for a pao < mmhg, the or was . [ . - . ] (p = . ). conclusion: in this study, we report a significant association between hyperoxemia at icu admission and mortality at d in patients with septic shock subjected to pre-hospital invasive mechanical ventilation. the adjustment of the pao is a crucial prognosis factor in patients with septic shock subjected to invasive out-of-hospital ventilation to avoid the toxic effects of hyperoxemia. however, blood gazometry is hard to get in a prehospital setting. consequently, alternative and feasible measures are needed, such as pulse oximetry, to improve the management of prehospital invasive ventilation. introduction: nowadays, benefit of enhanced ct-scan in positive diagnosis of acute pulmonary embolism (pe) is well established. it also allows evaluation of pe's burden on the right heart and shows several signs of acute cor pulmonale (acp). objectives -we aimed to assess benefits of control ct-scan h after thrombolysis in acute pe. patients and methods: we retrospectively enrolled patients with confirmed pe whom have been thrombolysed between january and august and controled with an enhanced ct-scan h after thrombolysis. assessement criteria were: qanadli obstruction index; signs of acp-right ventricle diameter left ventricle diameter (rvd lvd) and paradoxical interventricular septum (ivs). non inclusion criteria were: lack of initial or control ct-scan. results: during the study period ( years and months) we admitted patients from whom patients had acute pe ( . %). very severe patients that were thrombolysed as rescue therapy without initial ctscan and those who died before control ct-scan were not included. we enrolled patients-high risk mortality pe (n = , . %) and intermediate high risk pe (n = , . %). mean age was years and sex-ratio was . . at admission, mean severity scores were . ± . for saps ii and . ± . for apache ii. evolution criteria are listed in table . conclusion: control ct-scan is highly useful h after thrombolysis. it allows evaluation of response to pharmacological thrombolysis of acute pe and shows significative resolution of arterial obstruction degree and signs of acp. in december , after cancellation of the budget for a christmas tree, the nurses and caregivers of the night team spontaneously made and hung christmas decorations in our intensive care unit to make patients and their families feel better. the context was difficult with controversies around secularity. the town of paray le monial had been forced to remove a nativity scene and the city of melun had been criticized for setting one up. so we found it important to assess the perception of the approach by patients and relatives. patients and methods: decorations -hand-colored patterns about christmas theme printed on a paper decorations brought by the staff or already possessed by the unit-christmas balls, garlands, silver stardecorations made with service equipment-christmas tree consisting of inflated non-sterile gloves, cardboard, figurative nativity scene without a recognizable figure in a cardboard box with cotton, bed sheet to simulate snow. evaluation -all visitors and conscious patients received an anonymous single choice questionnaire with numerical scale and free fields from december th to december st, . results: answers were received, including-no negative opinion. neutral answer by a person who had not noticed the decorations. positive or extremely positive opinions. no answer without data. the comments pointed out the originality, the good idea, the warm comforting side. some asked for more decorations. others found them sober. the results show the good perception of the spontaneous action by the patients and their relatives. there was no negative response, particularly offend persons. however, it is possible that relatives or patients with negative opinions did not dare to express themselves. the initiative demonstrated a good cohesion of the night paramedical team, encouraging the interns and the day teams to take part in the coloring of the decorations. the initiative was initially aimed at the wellbeing of the patients and their relatives. however it has enabled an activity similar to preventing psychosocial risks among the healthcare team, allowing them to adopt a positive attitude in their approach to care. in addition, no significant costs were incurred thanks to the use of cheap materials, mainly recycled cardboard and standard quality white paper. the spontaneous decoration of our intensive care unit by the night care team was very well received by the patients, their families and their relatives. the initiative also made possible to enhance team cohesion and to value it. the associated costs were negligible. ventricular contractions. bp monitoring revealed a greater diastolic bp throughout h as well as during night-time. systolic bp higher than mmhg during sleep time was observed in % of participants. the frequency of arrhythmias and blood pressure variability are correlated with the increase in work stress and conflicts. conclusion: our results highlight the extent incidence of arrhythmia and blood pressure variability during intensive care unit night's shift probably due to the increased neuroendocrine stress response. ( %) and qrs enlargement ( %). ami was responsible for a significantly deeper coma (p < . ) but fewer seizures than clo (p = . ). three patients ( %) died. based on a univariate analysis, factors associated with death were cardiac arrest onset (p = . ), elevated plasma lactate concentration (p = . ), low arterial ph (p = . ), reduced pao fio ratio (p = . ) and prothrombine ratio (p = . ), increased aspartate aminotransferases (p = . ), alanine aminotransferases (p = . ) and serum creatinine concentration (p = . ) as well as marked catecholamine infusion rate (p = . ). the pharmacokinetic study showed significant increase in ami ( h vs. h) and clo ( h vs. h) elimination half-lives in overdose compared to pharmacological conditions, highlighting the contribution of organ failure to the delayed elimination of both toxicants. conclusion: ami and clo poisonings did not disappear and are still responsible for significant morbidities and mortality. ami was responsible for deeper coma with fewer seizures in comparison to clo. ami and clo elimination half-lives were significantly prolonged in overdose due to organ failure. introduction: severe poisonings and fatalities have been attributed to buprenorphine (bup) despite its ceiling respiratory effects, mainly if abused in co-ingestion with benzodiazepines. we previously showed that diazepam (dzp) bup combination induces severe respiratory depression in the rat, while each drug by itself does not. the objective of this study was to investigate the mechanisms involved in this drug-drug interaction using c-bup pet imaging and diaphragmatic electromyography in the sprague-dawley rat. patients and methods: c-bup was administered intravenously, mg kg unlabeled bup intraperitoneally and mg kg dzp subcutaneously. pet acquisition started with c-bup pet injection, min after dzp or its vehicle (veh + n = group) administration. suv normalized time activity curves (tacs) were generated and c-bup binding potential [bpnd, i.e. the ratio of the total receptor density (bmax) on the equilibrium dissociation constant (kd)] were modeled in different brain regions using a simplified reference tissue model with cerebellum as reference region. dem, implanted under anesthesia days before the experiment, was recorded during min in rats receiving veh veh, dzp veh, veh bup or dzp bup (n = group). after filtering and half-wave rectification, the first min auc of diaphragm contraction and workload were determined and compared between the groups. results: tacs and c-bup bpnd were not different between the dzp bup and the veh bup groups in all studied brain regions. diaphragm contraction was significantly increased in the veh bup group in comparison to the dzp bup group (p < . ). diaphragm workload was significantly increased in the veh bup group in comparison to the dzp veh and the dzp bup group (p < . and p < . respectively). discussion: dzp did not affect the c-bup brain distribution and brain binding suggesting that dzp does not affect bup transport across the blood brain barrier and bup receptors density affinity. bup administration induced an increase in diaphragm contraction and workload. this increase was inhibited in the presence of dzp suggesting that dzp bup combination-induced respiratory depression is mostly related to dzp. conclusion: respiratory depression related to dzp bup combination results from a pharmacodynamic drug-drug interaction. introduction: since the banning of dextropropoxyphene from the market, overdoses and fatalities attributed to tramadol, a who step- opioid analgesic, have increased markedly. tramadol overdose results not only in central nervous system (cns) depression attributed to its opioid properties but also in seizures, possibly related to nonopioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced cns toxicity. our objective was to investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose. patients and methods: sprague-dawley rats overdosed with mg kg intraperitoneal (ip) tramadol were randomized into four groups to receive solvent (control group), diazepam ( . mg kg ip), naloxone ( mg kg intravenous bolus followed by mg kg h infusion) and diazepam naloxone combination. sedation depth, temperature, number of seizures and intensity, whole-body plethysmography parameters and electroencephalography activity were measured. for each parameter, we compared the areas under the curves using mann-whitney tests for two-by-two comparisons between the four groups. regarding the effects of treatments on seizures, comparisons were performed using two-way analysis of variance followed by multiple comparison tests using bonferroni's correction. results: naloxone reversed tramadol-induced respiratory depression (p < . ) but significantly increased seizures (p < . ) and prolonged their occurrence time. diazepam abolished seizures but significantly deepened rat sedation (p < . ) without improving ventilation. diazepam naloxone combination completely abolished seizures, significantly improved rat ventilation by reducing inspiratory time (p < . ) but did not worsen sedation. based on the eeg study, tramadol-treated rats experienced electro-clinical seizures as soon as min after the injection, characterized by spike-waves and polyspikes with progressive decreased frequencies and inter-critical phases of slow delta waves until the next crisis. after diazepam naloxone injection, eeg waveforms consisted in hz-alpha rhythms and slow-down theta rhythms of drowsiness. none of these treatments significantly modified rat temperature. conclusion: diazepam naloxone combination is the most efficient antidote to reverse tramadol-induced cns toxicity. our experimental data greatly encourage administering this combination rather than naloxone alone as first-line antidote in tramadol-poisoned patients as an alternative to tracheal intubation. introduction: rubigine ® poisoning is a medical emergency that causes a major public health problem in underdeveloped countries, as it is frequently fatal. this poisoning is rare in france, but frequent in the french overseas departments (dom). the rubigine ® , made of fluoride and used as a rust remover, is the main source of poisoning in the caribbean. in martinique, the exact incidence of this intoxication is unknown, as there is no national and regional register. it could represent up to - % of severe acute poisoning. it was not until april that, following a prefectural order on the declaration, classification, packaging and labeling of substances, the composition of rubigine ® was modified to significantly reduce the mortality induced by its ingestion. the objective of our study was to describe the clinical features and complications that can occur after ingestion of rubigine ® as well as to determine the prognostic factors of death. we conducted a retrospective study over years, from to , including all patients admitted to emergency and intensive care units of the university hospital center (martinique) for acute rubigine ® poisoning. the usual demographic and clinical data were collected and comparisons between surviving and deceased patients were performed using a univariate analysis. results: fifty-five patients (mean age- years ( - ) + sex ratio male female- , ) were hospitalized at the university hospital of martinique. one-quarter of patients had no significant history. the average length of stay was . days ( - ). forty percent of patients experienced hypocalcaemia after initial intravenous calcium supplementation. complications included acute respiratory failure requiring invasive mechanical ventilation ( % of patients, duration of ventilation- . days, ( - )), renal failure ( %, of which % required extrarenal treatment, hemodynamic failure ( %), hepatic failure ( %), coagulation failure ( %), neurological failure ( %) and multi-visceral failure ( . %). three patients presented cardiogenic refractory shock requiring va ecmo ( . %) and another patient with digestive perforation ( . %). the mortality was . %, allowing the identification of prognostic factors of death. conclusion: rubigine ® poisoning is responsible for significant morbidity and mortality, despite optimal management. however, its incidence seems to have decreased sharply in recent years thanks to the strong mobilization and awareness of the population following the implementation of an information system by the university hospital 's clinical toxicology and toxico-vigilance unit, and different preventive measures introduced by the health authorities. introduction: since dextropropoxyphene withdrawal from the market, overdoses and fatalities attributed to tramadol, a who step- opioid analgesic drug, have increased markedly. besides central nervous system depression, tramadol overdose may result in seizures, usually included in the related serotonin syndrome. however, the serotoninergic mechanism of tramadol-induced seizures has been recently questioned. we investigated the effects of various specific pretreatments on tramadol-induced seizure onset and alterations in brain monoamines in the rat. patients and methods: sprague-dawley rats were randomized into five groups (n = group) to be pretreated with various agonists antagonists before receiving mg kg tramadol intraperitoneally- . mg kg ip diazepam + mg kg iv bolus followed by mg kg h infusion naloxone + mg kg ip cyproheptadine, and mg kg ip fexofenadine. seizure severity was graded according to the modified racine score ( ). we measured neurotransmitter concentrations in the frontal cortex using high performance liquid chromatography coupled to flurorimetry or radioenzymatic assay, as required. we used positron emission tomography-computed tomography to investigate interactions of tramadol with gaba-a receptors. the effects of treatments on seizures were compared using two-way analysis of variance followed by multiple comparison tests with bonferroni's correction. the areas under the curves of the effects on monoamine concentrations and the binding potentials in the pet-imaging study were compared two-by-two using mann-whitney u tests. results: diazepam abolished tramadol-induced seizures, by contrast to naloxone, cyproheptadine and fexofenadine pretreatments. interestingly, despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < . ), histamine (p < . ), dopamine (p < . ) and norepinephrine (p < . ) while no significant modifications were observed with the other tested pretreatments. based on positron emission tomography imaging using c-flumazenil fixation in the rat brain, we demonstrated molecular interaction between tramadol and γ-aminobutyric acid (gaba)-a receptors not related to a competitive mechanism between tramadol and flumazenil on the benzodiazepine binding site. our findings clearly ruled out the involvement of serotoninergic, opioidergic, histaminergic, dopaminergic and norepinephrinergic pathways in tramadol-induced seizures while strongly suggested tramadolinduced specific allosteric change in gabaa receptors that could contribute to seizures onset in overdose. conclusion: tramadol-induced seizures in overdose are mainly related to the gabaergic pathway. introduction: heparin-induced thrombocytopenia (hit) is a serious iatrogenic complication of heparinic treatments. the diagnosis of hit is difficult in the resuscitation environment because thrombocytopenia is a frequent and multifactorial phenomenon. the aim of this work was to study the clinical and biological presentation of patients with hit and the consequences attributable to hit on the evolution of patients in terms of morbidity and mortality and to develop a diagnostic strategy for hit for resuscitation patients. this was a retrospective, monocentric, descriptive and evaluative study conducted in our intensive care unit (icu) over a period of years months. an anti-pf antibody test was performed in patients who developed thrombocytopenia or a % drop in their initial platelet kinetics and the clinical picture. results: the incidence of hit was . % in patients hospitalized in icu. the clinicobiological severity scores, the reasons for admission to resuscitation were similar in both groups (hit+ and hit−) as well as the characteristics of the heparins used. the time of occurrence of thrombocytopenia was similar in the two groups. the diagnosis of hit was more often the only plausible diagnosis in the hit+ group. the t's score was significantly higher in the hit+ group. the evolution of the platelet count was similar in the two groups, in the decay phases as well as in the recuperation phase. hit+ patients showed significantly more thrombosis than hit− patients. there was no significant difference between the transfusion needs of hit+ and hit− patients. mortality was identical in both groups, as was the length of stay in icu. conclusion: hit is a rare disease. there was no evidence of a predisposing factor for the occurrence of the disease in a uniform resuscitation population. the diagnosis of hit is based on a cluster of arguments and not on an isolated event. biological tools are indispensable, in a complementary way to the clinical picture. pulmonary embolism in patients with sickle cell disease in intensive care unit: a challenging diagnosis jamoussi amira , zayet souheil , merhebene takoua results: during the study period, a total of patients with scd were admitted. among them, presented with respiratory distress and chest pain and then benefited first of trans-thoracic echocardiography that often showed right ventricle dilation and systolic pap > mmhg (n = ). all the patients underwent enhanced ct-scan and the diagnosis of pe was finally retained in cases ( . %) and hence colliged. the average age was . years ± . [ - years] with a sexratio = . the mean of apach ii score was . scd were diagnosed at the age of . years ± . [ - years] with a regular follow up in %. the reason for admission was acute respiratory failure in all cases. patients had clinical symptoms of pneumonia: pleuritic chest pain (n = ), dyspnea (n = ) and fever (n = ). all patients had a chest x-ray showing an alveolo-interstitial syndrome in cases ( . %) and an associated pneumonia in cases ( introduction: acute chest syndrome (acs) is the most severe complication of sickle cell disease and its evolution is unpredictable. acute pulmonary hypertension (ph) in acs is associated with an increased mortality, but its mechanism remains poorly known. our hypothesis is that acute ph is associated with a biological state of hypercoagulability in acs. in a prospective single center study, all consecutive scd patients with acs admitted to the intensive care unit (icu) of tenon hospital were included. specialized haemostasis dosages were performed on icu admission. a trans-thoracic echocardiogram was also performed on admission, and was repeated at steady state. results: among patients with acs, had a trans-thoracic echocardiogram and had a high echocardiographic probability of acute ph, including patient with bilateral pulmonary embolism and patient who developed multiple organ failure and died. there were no significant clinical, biological or radiological differences between patients with a low-intermediate probability of acute ph and those with a high probability of acute ph+ their evolution was similar. the exploration of haemostasis did not show between-group differences, regarding each parameter of haemostasis. however, when using a hierarchical cluster analysis, distinct profiles of coagulation were evidenced, defining biological classes. the subset of patients with a high echocardiographic probability of acute ph was more frequent in biological classes and which corresponded to hypercoagulability states. acute ph was transient in patients (n = ) with a repeated echocardiography at steady state. conclusion: acute ph may likely occur in patients with acs and a biological condition of hypercoagulability. further studies are needed to confirm these findings. gorham julie were the two independent predictors of survival after hospital discharge. in lung cancer patients admitted into the icu, the mgps is an independent predictor of survival after hospital discharge but not for mortality during icu stay. this inflammatory score could therefore be used as a long-term prognostic marker in this population of patients and would be more reflective of cancer, than reflecting the acute complication leading to icu admission. prospective and multicentric studies must be carried out to validate these results. introduction: recombinant active factor vii is a pro-hemostatic treatment used in obstetric haemorrhage, but no study has made it possible to specify its exact place in the decision algorithm. the objective of our work is to evaluate the efficacy and the benefit risk ratio of recombinant factor viia in the treatment of severe postpartum hemorrhage. we conducted a prospective study at the ibn jazzar university hospital in kairouan during the period from january , to december , . in total, we collected cases of recombinant factor viia in one postpartum haemorrhage. results: the mean age of our patients was + . years. the rate of childbirth was . %. the caesarean was the mode of delivery chosen for patients. the causes of postpartum haemorrhage in our series were-uterine atony in cases, uterine rupture and cervicouterine tear cases each, retroplacental hematoma and placenta accreta cases for each two and placenta praevia in cases. our patients were treated in an intensive care unit and the average hospital stay was . days. sulprostone was reported in cases ( . %), and all patients received a massive transfusion. the average time to administer rfviia was h min. the mean dose of factor vila recombinant was . ± . μg kg. five patients received a single dose, patients received a second injection and patients received doses. clinical efficacy-after a single injection, clinical efficacy with reduction in bleeding was observed in patients, i.e. %. the most frequent complication was insufficiencyrenal in cases including requiring hemodialysis, civd in cases, oap in cases, a multivisceral failure in cases, a septic shock in case and a mesenteric infarction in case. the progression was favorable in patients, while patients died ( . %). conclusion: it is important that new studies be carried out and shared experiences around the world on this drug appear to be effective and prevent invasive actions in the therapeutic arsenal of postpartum heamorrhage. introduction: post-partum haemorrhage (pph) is a life-threatening complication and remains a leading cause of maternal morbidity worldwide. the woman trial* estabished that early administration of tranexamic acid (ta) reduces mortality due to the bleeding in women with pph. our study purpose was to determine the effects of early administration of ta and fibrinogen concentrate on death, hysterectomy and transfusion in women with severe pph. patients and methods: this retrospective, monocentric study was performed in a third level tunisian hospital providing healthcare for more than pregnant women per year. were included in this study women with diagnosis of severe post partum haemorrhage after a vaginal or caesarean delivery from to . patients who received ta and fibrinogen concentrate were assessed in group (g ) and who not in group (g ). results: the incidence of severe pph was / deliveries. women were retained for data analysis g (n = ), g (n = ). anthropomorphic and obstetrics characteristics were not significantly different between the two groups. there was a significant difference between the two groups regarding to transfused units of red blood cells however, no difference in term of the use of frozen plasma and platelets concentrates was observed. perioperative hemoglobin nadir was significantly higher in g . the frequency of hysterectomy and pelvic packing were higher in g (table ) . no thromboembolic events and no haemorrhage related mortality were observed in the two groups. conclusion: in this retrospective study, early administration of tranexamic acid and fibrinogen reduces risk of hysterectomy transfusion. these encouraging results strongly support the need for a large, international, double-blind study to investigate the potential of the association "ta-fibrinogen concentrate" to reduce maternal haemorrhage related morbidity and mortality. introduction: immunodeficiency, acquired or congenital, is the first comorbidity associated with poor outcome in pediatric patients with acute respiratory distress syndrome (ards). the aim of this study was to describe outcome of pediatric patient with hematologic disease hospitalized in our intensive care unit for respiratory failure and to investigate the clinical variables associated with mortality. patients and methods: it was a retrospective monocentric descriptive study including all immunodeficient pediatric patient (malignant hemopathy, congenital immunodeficiency, bone marrow transplanta-tion…) from hematology hospitalized in our beds pediatric intensive care unit with the diagnosis of respiratory failure between january and february . results: fifty one patients were included corresponding to admissions. nighty percent of the patients met criteria for pediatric ards- % were severe, % moderate and % mild. extracorporeal circulation (ecc) was needed for patients. global mortality rate at picu discharge was %. twenty four patients ( %) received noninvasive ventilation (niv). height of them ( %) did not need invasive mechanical ventilation (imv). in patients who received imv, mortality rate was significantly higher if patients received before niv ( vs. %) p = . . all patients who needed imv after more than h of niv died (n = ). mortality was higher in children with griffon versus host disease ( vs. % p = . ). mortality of patients receiving ecc and renal replacement therapy (rtt) was respectively and %. conclusion: in our study, most of the patients hospitalized for respiratory failure met criteria for pediatric ards. if niv decrease imv requirement, it could be associated with higher mortality rate in case of failure. this result support recent recommendation that immunodeficiency is not a sufficient criteria to delayed imv. . flow and airway pressure were recorded at the asl inlet and mouth pressure into the manikin mouth. we defined "device driving pressure" as the peak mouth pressure minus the tele-expiratory mouth pressure. continuous data are reported as mean ± sd. results: as compared to the oxygen mask, vt increased significantly with m-niv and h-niv whatever the simulated respiratory effort ( ± and ± vs. ± ml respectively with the moderate simulated effort, p < . ; fig. ). hfnc and cpap were associated with a slight but non-significant decrease in vt as compared to the oxygen mask. overall, for a given respiratory effort, vt was influenced by the "device driving pressure", which tended to decrease when using hfnc and cpap and markedly increased with m-niv as compared to the oxygen mask. therefore, vt in m-niv with a simulated low effort was significantly higher than vt in cpap and hfnc with a simulated moderate effort ( ± ml, ± ml, and ± ml respectively, p = . for both comparisons). conclusion: in our bench model, the vt value was significantly influenced by the noninvasive ventilatory device. niv was invariably associated with significantly higher vt than with other devices, even when dividing by two the simulated inspiratory effort during niv. introduction: in icu, intubation is a high risk procedure associated with high morbidity. despite procedure's improvement with systematic application of fluid loading, early use of vasopressors and checklist use, morbidity remains high. several recent trials has been conducted with different metrics choose as primary outcome. however any evidence exists to choose one more than another: time to intubation, first pass success, difficult intubation. first pass success sine hypoxia and hypotension (dash- a) has been highlighted recently and choose by the game program without any scientific evaluation. we conducted a post hoc analysis of the randomized clinical trial macgrath mac video laryngoscope or macintosh laryngoscope for intubation in the intensive care unit (macman) to determine the best metric to choose for primary outcome for the next intubation studies in icu. patients and methods: macman was a multicentre, open-label, randomized controlled superiority trial. consecutive patients requiring intubation were randomly allocated to either the mcgrath mac videolaryngoscope or the macintosh laryngoscope, with stratification by centre and operator experience. an only inclusion criterion was-"patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if-contraindication to orotracheal intubation (e.g., unstable spinal lesion) + insufficient time to include and randomize the patient (e.g., because of cardiac arrest) + age < years + pregnant or breastfeeding woman + correctional facility inmate + patient under guardianship + patient without health insurance + refusal of the patient or next of kin to participate in the study + previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess association and prediction of life threatening complication (mild to moderate, severe, mild to severe) by different metric existing-time to intubation, first pass success, difficult intubation, first pass success sine hypoxia and hypotension. each metric was compared with another one. area under curve was built for every metric and all metrics were then compared. results: dash- a was superior to all others metrics included in the analysis for prediction of life threatning complications (all p < . ). failure of first pass conclusion: all metrics are not equal to predict severe life threatening complications during intubation in the icu. in this context, we recommend adoption of definitive airway sine hypoxia or hypotension at first attempt (dash- a) as primary outcome for intubation studies in the icu or as metric indicator tracked in quality improvement program. benbernou soumia introduction: introductionacute respiratory failure (arf) is a common cause of emergency use and one of the major reasons for admission to intensive care unit. it associates a vital risk imposing immediate symptomatic treatments and an etiological approach. [ ] among the etiologies of the arf, acute lung edema (ale), decompensation of chronic obstructive pulmonary disease (copd), chest trauma and pneumonia are the most frequent @it is a life-threatening pathology with a high incidence of mortality, since mortality is reported to be - % [ , ] for arf secondary to cardiogenic ale. the prevalence of arf in algeria remains unknown + the tahina study showed that respiratory diseases were the leading cause of consultation in the hospital [ ] . the the objective of this study is to estimate the frequency of use of the niv and to determine the associated factors of failure of the niv for the adult patients hospitalized for arf in the emergency department of oran hospital from january to november . prevalence of copd was found in the . % of tobacco subjects [ ] . the number of patients hospitalized for chest trauma continues to increase, resulting in an increase in the number of patients admitted for arf secondary to chest trauma. patients and methods: this is an observational and exhaustive study during the month of november, from the files of patients. the population-all subjects over years hospitalized for an arf at the reception and resuscitation units of the emergency department of oran hospital from january to november . results: ninety-seven patients were hospitalized for arf during this period. niv was used for patients. patients were acute lung edema. univariate analysis showed that spo was the only failure factor in this series. the failure rate of this technique was . %. niv is a technique that should be used more in the emergency rooms, which would make it possible to use less intubation specially in indications where the level of proof in the literature is important. demographic characteristics, etiology of exacerbation, comorbidities, the sapsii score, arterial blood gases at admission, respiratory, hemodynamic and neurological parameters, use of noninvasive or invasive ventilation, nosocomial infection, duration of niv, length of stay and mortality. results: during period study patients ( % women with a sapsii score ± ) were included. the etiology of exacerbation was bronchitis in % of cases and pneumonia in %. only patients have niv at home and patients have oxygen. pseudomonas aeruginosa was isolated in cases. twenty percent of the patients had developed a nosocomial infection, acinetobacter baumanii and pseudomonas aeruginosa were isolated in and % respectively. niv was used in patients at admission and the rate of niv failure was %. the duration of mechanical ventilation was ± days and the length of stay was ± days. the mortality was %. niv and oxygen at home were prescribed for patients. in univariate analysis survivors and non-survivors were comparable regarding baseline and clinical characteristics. nosocomial infections ( vs. %), and spassii score were significantly more elevated in non-survivors. in emergency department, the management of hypercapnic acute respiratory failure with hfo is limited. hypercapnia and acidosis remain moderate. patients are old with comorbidities. the mortality rate is high but expected given the number of limitation of active therapy. hfo appears to be effective for a majority of patients, but half of them required niv too. the niv hfo association seems an interesting option. but our methodology is perfectible and would require a randomized control tria. severe chronic obstructive pulmonary disease with chronic respiratory failure in intensive care unit: mortality and prognostic factors arnout chloé , faure morgane , novy emmanuel chu nancy, nancy, france correspondence: arnout chloé -arnout.chloe@gmail.com introduction: last decades, the number of patient with chronic respiratory failure due to chronic obstructive pulmonary disease (copd) admitted in intensive care unit (icu) increased. data about their real prognosis in the icu are lacking. the objective of this study was to evaluate mortality rate at months and to identify prognostic factors of copd patients with chronic respiratory failure, treated with long term oxygen therapy (ltot), admitted in icu. patients and methods: a retrospective cohort study was conducted in the french university hospital of nancy during years - on all copd patients treated with ltot admitted in icu. only the first admission was analysed. patients were included if they had spirometry, blood gas and oxygen flow in the year before admission in icu. other causes of chronic respiratory failure, and patients with tracheostomy before icu admission were excluded of the cohort. hospitalizations were selected using the international classification of diseases, th revision (icd- ). results: one hundred and thirteen patients were included, ( %) died in the first months after icu admission. mortality rate in icu was %. severity of copd was-mean bode score ± . , number of exacerbation per year requiring hospitalization ± . . ltot was used for . ± . years. acute respiratory failure was the main frequent cause- % pneumonia, % acute exacerbation of copd, % acute lung oedema. the sequential organ failure assessment score within the first h of icu admission was ± . need for mechanical ventilation was noted in % of cases and was associated to mortality with an odds ratio of . (ci % [ . - ] p = . ). in presence of other organ failure, mortality rate tends to increase. patients with median pao fio ratio > on first blood gas had a reduced risk of death (or . + ci % [ . - . ], p = . ). conclusion: this is the first study to assess mortality at month of patients with severe copd requiring ltot admitted in icu. severity of hypoxemia and use of mechanical ventilation are two prognosis factor of mortality. the addition of another organ failure seems to increase the mortality rate. severity of the chronic respiratory insufficiency less influenced short and long term outcome. this data have to be included in the global decision to admit a copd patient with ltot in icu. introduction: the remarkable progress in the outpatient care of the asthmatic patient (development and access to inhaled drugs) has made the admission of these patients exceptional in the icu. we have noticed a recent upsurge in asthmatic afmissions in the icu, and are investigating whether this fact was related to modifiable factors (access to adapted drugs) or an increase in the severity of the disease. patients and methods: retrospective, observational, three-center study conducted in three tunisian medical icu from january to july, . were included all consecutive patients admitted for severe acute asthma in three icus. were assessed-patient's demographic characteristics, asthma severity and its actual control based on global initiative for asthma classification (gina) , clinical characteristics of the acute episode, length of icu stay, ventilatory free days and mortality. results: out of the patients admitted within the study period, ( %) had severe acute asthma. the mean age was years (iqr - . ). sex ratio was . asthma was allergic in % with an average ancienty of . years. over all asthma was not very severe with no prior icu admission for acute severe asthma . % were mechanically ventilated at least one time. were classified severe and moderate persistant asthma respectively in . (%) and (%). . % were consideredpoorly controlled. low educational level and socio-economic status are the main determinants of poor control- % of analyzed patients didn't have a social care, and thus no accesse to prescribed anti-asthmatics + % didn't have a regular follow up and . % were jobless. when admitted to the icu- patients ( . %) needed invasive mechanical ventilation, one patient received niv. the mean length of stay was days (iqr . - . ). levels of auto peep and pic pressure at icu admission were respectively (iqr - ) and . (iqr , - . ) cm h o. mortality rate was %. this study suggests that low educational level and socioeconomic status (especially the lack of social care and joblessness) are the main determinants of poor control of asthma and may lead to the increase of rate of icu admission for severe acute asthma requiring mechanical ventilation. introduction: in emergency medicine, the boussignac system (bs) is sometimes used to administer oxygen and continuous positive airway pressure (cpap). in this case, fio value depends on the ratio between o flow and inspiratory flow (if). in some cases, the fio decreases due to the if increase. the aim of this study was to test a modified boussignac system in order to limit the fio decreases during inspiratory flow rate increases. the study was conducted on bench with bs connected to a two compartment adult lung model (dual test lung ® ) (dtl) controlled by a maquet servo i ® ventilator. three minute ventilation (mv- . . l min) with ti ttot = . were investigated. fio and mv measurements were made using an iworx ® ga gas analyzer. with a bs, two peep were analyzed- and cm h o. the bs was supplied by an o flow. in order to increase the fio , we have evaluated the addition of a t piece connected to a nebulizer at the air-room admission of a bs. the aerosol was supplied by an o flow of l min. the o flow was analyzed in continuous with a calibrated mass flow meter (red y vogtlyn ™ ). results: when mv increases, the fio decreases (p < . ). when peep increases, fio increases too (p < . ). the addition of an aerosol (o - l min) to a bs increases the fio (p < . ). however, in this last case, the gap between both fio decreases with increases mv (fig. ) . the addition of an aerosol connected to an o flow rate ( l min) at the entry of a bs limits the fio decreases during the mv increases. introduction: burned patients are at high risk of yeast colonization and thus of invasive fungal infections, particularly to candida (c.) spp., leading to an increase in morbidity and mortality. while pre-emptive antifungal therapy has improved survival, it may lead to an increase in antifungal resistance. the objectives of this work were to describe candida species distribution and to determine the antifungal susceptibility of candida isolates acquired in a burn unit. our study is a retrospective review of severely burned patients admitted to the burn unit of the ben arous traumatology and burns center with one or more positive culture sites for candida, during the -month period from may through august . a total of isolates were thus obtained. the susceptibility to antifungal drugs ( -fluorocytosine, fluconazole, ketoconazole, micronazole, itraconazole, amphotericin b) was determined using the fungitest ® broth dilution method for patients with infected normally sterile body sites or a candida colonization index superior or equal to . . since echinocandin and anidulafungine were recently introduced in tunisia, the susceptibility to these antifungal classes was tested for only one patient from our cohort. results: nasal and buccal sites were the most colonized body sites ( . % each), followed by axillary ( . %) and rectal sites ( . %) and urines ( . %). c. albicans was the predominant species ( . %), followed by c. glabrata ( . %), c. tropicalis ( . %) and c. parapsilosis ( . %). among the strains whose antifungal susceptibility was determined, majority of candida isolates were susceptible to fluconazole ( . %), which is the most frequently used molecule as a pre-emptive treatment in such cases in tunisia due to its availability and its efficiency. on the other hand, . % of the isolates were intermediate and . % were resistant to this antifungal drug, mainly c. glabrata for both groups. as for the other tested azoles, high rates of intermediate strains were noticed ( . % to itraconazole, . % to ketoconazole and . % to miconazole), mostly c. glabrata. only one strain was resistant to amphotericin b, which is not usually used in these cases due to its nephrotoxicity and the frequency of kidney failure in burned patients. our study demonstrates that c. albicans is the most frequent species in burn unit-acquired candidiasis. no major antifungal resistance was observed, apart from high rates of intermediate strains (mainly c. glabrata) to azole class antifungal drugs. introduction: infection, especially bacteremia, is a major cause of morbi-mortality in severely burned patients. mortalityrelated to bacteremia in burn patients was about % [ ] . we performed this study to determine the prevalence, the causative agents and outcomes of bacteremia in burned patients. introduction: carbapenems, the last line of therapy, are now frequently needed to treat nosocomial infections, and increasing resistance to this class of β-lactams limit antibiotic options in critically ill patients especially in burns. the objective of our study was to assess the impact of the detection of carbaménépases in optimizing treatments in burned. patients and methods: a prospective, monocentric study was carried out at the intensive care unit of burn in tunisia over months (march-august ). were included all patients who have had a carbapenemase research. the sample was carried out by rectal swab. all samples were analyzed by polymerase chain reaction (pcr) methods for presence of carbapenemase. during the study period, patients were included. the mean age was ± years. they were men and women. the average burned surface area was ± %. patients were transferred from another hospital structure in % of cases with a delay of h. % of patients had a septic complication with a delay of ± days. antibiotic treatment was empirical in cases. the therapeutic failure rate was %. results of carbame-nepases detected by pcr are detailed in table . in the group of patients pcr (+), the antibiotic treatment was changed in cases. the most association of antibiotics were-tigecycline in combination with colistin or in combination with fosfomycine and fosfomycin in combination with colistin. this leads to reduce therapeutic failure by %. conclusion: detection of carbapenemase in our study was higher ( %), allows us to identify regions with high risk of carbapenemase, improve therapeutic efficacy and strengthen infection control measures by isolation of all carbapenemase producing patient. introduction: icu-acquired bacteraemia is prevalent and poses a grave threat. providing information about the main causative bacterial agents and determination of their susceptibility to antibiotics may improve empiric therapy and early detection of emerging antimicrobial resistance. the aim of this study was to investigate the species distribution and antibiotic susceptibility of isolated strains from blood culture in burn intensive care unit during a five-year period. patients and methods: from january to december , a total of , non repetitive strains were isolated from blood cultures. incubation of blood culture vials and the detection of bacterial growth were performed by the bactec system. all isolated organisms were identified on the basis of standard microbiological techniques. antibiotic susceptibility testing was carried out by the agar disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm and guidelines. data were analyzed using the sir-system. minimum inhibitory concentrations of colistin, imipenem and vancomycin were determined using the etest ® method (biomérieux). results: of the , strains isolated, the most frequently identified species were staphylococcus aureus ( %), acinetobacter baumannii ( %), klebsiella pneumoniae ( %), and pseudomonas aeruginosa ( %). the rate of methicillin-resistant staphylococcus aureus (mrsa) was %. resistance to tigecycline and linezolid was and %, respectively. all strains were susceptible to glycopeptides. in addition, isolated acinetobacter baumanii strains showed high rates of resistant to all tested antibiotics except colistin. eighty per cent of these strains were resistant to ceftazidime and % to imipenem. resistance to rifampicin was % in , and has increased steadily to % by . similarly, high resistance rates were observed among klebsiella pneumoniae and pseudomonas aeruginosa to ceftazidime ( and % respectively), ciprofloxacin ( and %) and imipenem ( and %). conclusion: this study investigated on the local distribution patterns of causative organisms of bacteraemia in burn patients and the corresponding antimicrobial susceptibility profiles. multidrug-resistant pathogens, especially mrsa and acinetobacter baumanii, were the most frequently isolated organisms. hygiene measures and antimicrobial stewardship should be implemented to prevent the spreading of these resistant strains. introduction: pseudomonas aeruginosa is known opportunistic pathogen frequently causing serious infections in burned patients. multidrug resistance in this pathogen is increasing throughout the world and is a major problem in the management of these pathogens. analysis of serotype and resistance profile to antobiotics of p. aeruginosa help to establish a prompt control and prevention program. the aim of this study was to evaluate the frequency of antimicrobial resistance and the prevalence of pseudomonas aeruginosa serotypes isolated in the burn unit. patients and methods: during a period of years (from to ), strains of pseudomonas aeruginosa were isolated from burned patients. conventional methods were used for identification. antimicrobial susceptibility testing was performed with disk diffusion method and susceptibility data were interpreted according to breakpoints recommended by the french society of microbiology (fsm). serotypes were identified by slide agglutination test using p. aeruginosa o antisera (biorad). the imipenem-resistant strains have benefited from a research of carbapenemase production by the edta test. results: in our study period, bacterial isolates were found among which pseudomonas aeruginosa was the second most frequent bacterium isolated from burned patients ( %) after staphylococcus aureus ( %). the most frequent sites were-cutaneus infection ( %), blood culture ( %) and catheter ( %). the most prevalent serotypes were-o ( %), o ( %), o ( %), o ( %) and o ( %). the survey of antibiotic susceptibilily showed high pourcentage of resistance to the different antibiotics- % of strains were resistant to ceftazidim, % to ticarcillin, % to ciprofloxacin, % to amikacin and % to imipenem. among the imipenem resistant strains, % were metallo-beta-lactamase producers. the antibiotic to which p. aeruginosa was the most susceptible was colistin ( %). multidrugresistance was associated with o serotype in % of the cases. the global frequency of serotypes o , o and o was more than %. multidrug resistance and carbapenemase being associated with serotype o . serotyping of the strains isolated from burned patients will help to guide the first antibiotherapy. the dissemination of carbapenemases strains must be contained by implementation of timely identification, strict isolation methods and better hygienic procedures. and respiratory disorders ( . %)…). the therapeutic management was based on per operative resuscitation, organ failure treatment, probabilistic antibiotic therapy and median laparotomy surgery. the main etiologies of abdominal sepsis were-digestive perforations ( . %), purulent effusion ( %), intestinal necrosis ( %), cholecystitis ( . %). the bacteriological profile was -predominance of bgn ( . %) dominated by e. coli ( %) followed by klebsiella pneumoniae and acinetobacter baumanii ( . %), the mean duration of the hospitalization was . ± . days. the mortality rate was %. the main prognostic factors in our study in univariate analysis were-the advanced age, the diabetes, the organ failure, the increased gravity scores, the time to management, the use of catecholamines and the development of septic shock. the multivariate analysis showed a statistically significant association between the development of septic shock, the stercoral effusion, the peptic ulcer perforation, the operator and the therapeutic descalation. the abdominal sepsis is a serious affection, with great mortality. the improvement of its prognosis is based on a revision of the medical and surgical protocols, and an adapted antibiotic therapy depending on the direct examination of the samples, also of the bacterial ecology of the service. introduction: severe acute respiratory infections (sari) are common in critically ill patients. viruses can be found in immuno-competent patients. however, the main problem for viral infections is the diagnosis, isolation of the pathogen is often difficult and the symptoms not specific. the aims of this study were to describing the epidemiological characteristics of viral respiratory infections, to identify factors predictive of a poor outcome. introduction: in septic shock there are physiological changes with an increase in the volume of distribution, with implications for pharmacokinetics of antibiotics that make recommended doses potentially inadequate for target organisms with highest minimal inhibitory concentrations. to cover these bacteria, peak serum concentration (cmax) target is - pg ml. identification of predictive factors for insufficient cmax, in common practice, would make it possible to target the patients at risk in order to optimize dosage of antibiotic to be administered. objective of this study was to determine predictive factors of amikacin's cmax insufficient independently of the dosage. patients and methods: this was a retrospective study carried out between august and november in icu of our hospital. all adult patient receiving an initial injection of amikacin between and mg kg were included. clinical data collected were-amikacin dosage, body mass index (bmi), mechanical ventilation (mv), mean arterial pressure (map), use of noradrenaline and continuous hemofiltration (cvvh). biological elements were collected and for each, the last result in the h prior to admission and that at the patient's entry into icu were added to analysis. a comparison of this clinical and biological variables was made between two groups-the first one with an ineffective cmax of amikacin (< pg ml) and the second with an effective cmax of amikacin (> pg ml). results: patients were selected for statistical analysis. median dosage was . mg kg for a median cmax at . mg l. for patients, cmax was less than mg l and in patients, it was greater than mg l. there was a statistically significant relationship between a cmax greater than mg l and mv, bmi, pct measured before and after admission, albumin after admission, hemoglobinemia, hematocrit level after admission, the rate of urea after admission (table ) . a low bmi was associated with cmax < mg l. discussion: these results remain comparable to those found by taccone in , with dosages of mg kg having only % of the peaks above mg l + comparable also to montmollin's study in . conclusion: mv, bmi, pre-and post-admission pct, and albumin, hemoglobin after admission, hematocrit and urea after admission seems to be predictive criteria for insufficient amikacin's cmax independently of dosage. our study was limited to one icu, a heterogeneous recruitment, and that all samples have been taken at the right time. introduction: this study aimed to assess whether augmented renal clearance (arc) impacts negatively on ceftriaxone pharmacokinetic pharmacodynamics (pk/pd) target attainment in critically ill patients receiving g day by intermittent infusion. patients and methods: over an -month period, all critically ill patients treated by ceftriaxone for a first episode of sepsis without renal impairment were eligible. during the first days of antimicrobial therapy, every patient underwent -hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at trough concentrations. the main outcome investigated in this study was the rate of empirical target non-attainment using a theoretical target mic of mg/l. results: over the study period, patients were included ( samples analyzed for therapeutic drug monitoring). the rate of pk/pd target non-attainment was %, with a strong association with crcl (p < . ) ( table ). there was no statistical association between pk/ pd target non-attainment and therapeutic failure. conclusion: when targeting %ft > mic of the less susceptible pathogens, patients with crcl > ml/min are at risk of subexposure in ceftriaxone ( g day). these data emphasize the need of therapeutic drug monitoring in patients with arc, especially when targeting less susceptible pathogens or surgical infections with limited penetration of antimicrobial agents. introduction: the septic shock is a major concern of the intensive care unit in the world because of its frequency and especially of its mortality which remains high in spite of the progress made in the optimizing care. the aim of our work is to analyze the prognosis factors related to death among patients with septic shock in the icu of the military hospital avicenna of marrakesh, and to focus on the physiopathological and therapeutic data of the septic shock in the light of last acquisitions in this field. patients and methods: we proceed to a prospective study including all patients with septic shock at admission to icu or secondary, over a -year period (january -december ). prognosis factors related to death in patients with septic shock were studied in univariate and multivariate analysis. results: eighty-six cases of septic shock were collected from icu admissions, the incidence is . %, the mean age was ± . . the sites of infection most often involved were the abdomen and lung ( %), there was a predominance of gram-negative bacilli, the number of organ failure is in average . ± . . the overall mortality was . %. prognosis factors related to mortality retained after logistic regression are cardiovascular organ failure followed by neurological. indeed, the number of patients with or more failures was ( %) in the group of patients who died. as the second factor influencing the high mortality found severity score . ± . , age is also considered a prognosis factor since of patients were over years. the average age of the deceased was ± years versus ± years in survivors (p < . ), yet the mortality according to the infectious agent was not found as factor influencing mortality (p = . ). conclusion: septic shock is a frequent reason for hospitalization in icu. the improvement of prognosis requires an early and adapted management of sepsis as well as increases efforts for control and prevention of nosocomial infection. introduction: vitamin d deficiency is common in critically-ill patients. in addition to its role in the regulation of phosphor-calcic metabolism, vitamin d is of paramount importance for the immune system. the aim of the current study is to assess the prognostic value of vitamin d deficiency in patients with septic shock. patients and methods: retrospective study conducted over months. all the adult patients with septic shock and vitamin d level screening performed within the first h of admission were included in the study. we excluded patients with chronic kidney disease and those receiving vitamin d supply. two groups were compared: those with a serum vitamin d level < ng/ml (g ) and those with higher level (g introduction: since immunity plays a central role in neoplasms surveillance, it is likely that sepsis induced immune dysfunctions may impact on the underlying malignancy. we developed a research project investigating the reciprocal relationships between bacterial sepsis and cancer. we reported that sepsis-induced immune suppression promoted tumor growth in post-septic mice inoculated with cancer. in a reverse cancer-then-sepsis model we observed that sepsis may conversely inhibit tumor growth. this study aimed at investigating the cellular and molecular mechanisms of sepsis-induced tumor inhibition, and most especially the role of monocytes macrophages and toll-like receptor (tlr) signaling. patients and methods: we used c bl j wild-type (wt), tlr -/-, tlr -/-and myd -/-mice. mice were first subjected to tumor inoculation by subcutaneous injection of mca fibrosarcoma cells. fourteen days after, mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (clp). controls were cancer mice subjected to sham surgery. alternatively, cancer mice were subjected to an i.p. challenge with tlr agonist (lps or heat-killed staphylococcus aureus (hksa)). the distribution of tumor-associated immune cells was assessed by facs at days and following surgery. the activation status of tumorinfiltrating monocytes macrophages was assessed by facs (mhcii, cd , cd , pdl , pd ). f / + cells were purified by facs and we assessed cytokines production (rt-qpcr) and bacteria phagocytosis. we confirmed polymicrobial sepsis dampens tumor growth in wt mice. a similar clp-induced tumor growth inhibition was observed in tlr -/-mice, but neither in tlr -/-nor myd -/-mice. a challenge with lps resulted in a marked anti-tumoral effect, whereas a challenge with hksa had no impact on tumor growth. tumor-infiltrating immune cells analysis retrieved monocytes/macrophages predominance with two different subsets based on f / expression (f / high and f / low). late-onset (day ) tumors from clp-operated mice displayed increased proportions of f / high. as compared to f / low cells, f / high cells displayed a more immature status with a lower expression of cd , mhcii and pdl , and a higher phagocytic activity. interestingly, f / high cells from clp-operated mice exhibited a higher phagocytic activity than those from sham-operated mice. conclusion: polymicrobial sepsis drives a potent antitumoral activity in cancer mice, which is associated with changes in the distribution and functions of tumor-associated monocytes macrophages subsets. our results converge on a critical role of tlr signaling, that should be further investigated. conclusion: post-agressive immunosuppression in icu is not specific to sepsis. in septic shock, the low counts in circulating ilc s could be explained by ilc plasticity (conversion of these cells into ilc s), by migration from the blood or by an exacerbated apoptosis. ilc s expansion, associated with a higher risk of secondary infection, could be promoted by il- , released by tissue injuries. ilc s could activate regulatory t cells via il- . these preliminary results must be confirmed on a larger cohort. they play a suppressive role in the immune system by the secretion of negative regulatory cytokines such as interleukin- or by immune cell contact inhibition. the objective of this pilot study was to develop and test a protocol to determine the breg level in septic patients. the level of breg were measured on whole blood sample by flow cytometry the first day of hospitalisation in septic patients. b cells were identified on the single-parameter expression cd combined with scatter. the breg were identified as subpopulation expressing cd /hicd hi or cd /hicd + (see fig. ). the results were expressed as percentage of the parental lineage gate and absolute value per microliter. this protocol has been optimised in order to be able to transfer technic into clinical practice. results: we include patients hospitalized in intensive care unit with severe sepsis or septic shock. the percentage of cd + cd hic-d hi was . ± . % with a mean of . ± . cells microliter. the percentage of cd + cd hicd + was . ± . % with a mean of . ± . cells microliter. we are able to measure and follow the evolution of breg during severe sepsis or septic shock. because breg could inhibit body immune function, we wish to conduct a prospective study to evaluate the correlation between breg level and the prognosis of patients with sepsis. the neutrophil/lymphocyte ratio (nlr) reflects an inflammatory state. the nlr has recently emerged as a prognostic marker in colorectal cancer patients, acute coronary syndrome and pulmonary embolism (kayrak m, heart lung circ ). the aim of this study was to assess the prognostic value of nlr in patients with septic shock. we performed a prospective observational study in septic shock icu patients within h of admission from january to july in charles nicolle hospital of tunis. exclusion criteria were age < years, pregnancy + oncohematological patients, recent blood transfusion, post-cardiac arrest and brain-death. nlr was measured soon after admission and h, h, and h after. demographic, clinical and biochemical parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of icu stay were recorded. the primary endpoint was -day mortality. results: sixty-five patients ( males, median age, . years) with septic shock were included in the study. the -day mortality was %. the median sofa score at t was points and the median igs score was points. the sources of infection were as follows: the lungs (n = ), the urinary tract (n = ), the central nervous system (n = ), the abdomen (n = ), skin and soft tissue (n = ). the parameters that were identified through univariate analysis to be associated with -day mortality were igs score, lactate level, the nlr elevation at h , h and h . median nlr levels were significantly higher in non-survivors (n = ) than survivors ( introduction: the autonomic nervous system (ans) is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of ans activity and a relation between hrv and outcome has been proposed in various types of patients. we evaluated the feasibility of a automated hrv monitoring, based on standard electrocardiography monitoring, and investigated the different parameters that should be recorded. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct ) that aims to record more than icu patients over a -years period. patients and methods: physiological tracings were recorded from the standard monitoring system (intelliview mp philips), using a dedicated network and extraction software (synapse v , ltsi inserm u ) that enables simultaneous recording of different physiological curves, at their native resolution ( hz for ecg, hz for other). raw data were subsequently stored on a dedicated local server, before anonymization and analysis. all consecutive patients were recorded for a -hours period during the -hours following icu admission. all measurements were recorded with the patient laying supine, with a ° bed head angulation. physiological recordings were associated with metadata collection by a dedicated research assistant. hrv parameters were derived from electrocardiography monitoring using kubios hrv premium ( introduction: acute cor pulmonale (acp) is a frequent complication of acute respiratory distress syndrome (ards). it occurs in % of cases and might be associated with an increased mortality rate. it is defined by a ratio of telediastolic surfaces of right ventricular (rv) on left ventricular greater than . and a septal dyskinesia. however, systolic dysfunction defined by the guidelines of the american society of echocardiography has not been well studied in ards and in particular concerning the rv free wall longitudinal strain (rv-fw-ls). the aims of the present study were to identify the prevalence of rv systolic dysfunction and acp in ards, and to evaluate the effects of inhaled nitric oxide (noi) and prone positioning. we prospectively included patients to a mild to severe ards, and proceeded to standardization of ventilation and systematic echocardiography in semirecumbent position, with noi and in prone position. interpretation of examination was blinded to the investigator. we evaluated the presence of acp, systolic dysfunction identified by classical cardiologic criteria (rv fractional area change, rv tei index, tricuspid annular plane systolic excursion, velocity of the tricuspid annular systolic motion) and also by rv-fw-ls. results: sixteen patients were included. thirty-seven percent of patients were in severe ards. the prevalence of acp was % while right ventricular systolic dysfunction was identified in . % of patients with the classic cardiologic criteria and . % with the impairment of rv-fw-ls which represented the most sensitive test for right ventricular dysfunction detection (table ) introduction: the use of extra corporeal membrane oxygenation (ecmo) is increasing. brain complications may occur, resulting in an increased morbidity and mortality. the objective of our study was to analyze the incidence of neurological complications while receiving ecmo, the risk factors, and to describe morbidity and mortality in a large cohort of patients in intensive care unit. patients and methods: this was an observational, mono-centric, -year retrospective study in patients who received ecmo. primary outcome was the occurrence of neurological complication until d after ecmo. results: one hundred and eight patients were included in the analysis. twenty-seven patients ( %) presented a neurological complication. of these, died at d . there were ischemic sequelae ( . %), intracranial haemorrhages ( . %), cerebral edema ( . %) and one other lesion ( . %). the median time before occurence of a neurological complication was days after the implementation of ecmo. multivariate analysis revealed the presence of hyperlactatemia > . mmol l, neurological deficit at the beginning of the management, as well as the history of stroke before the ecmo implementation as predictive factors of neurological complication (or . , . the incidence of neurological complications under ecmo is about % and ischemic sequelae are the most frequent. history of stroke and low cerebral flow associated with ischemia-reperfusion seem to increase the occurrence of these complications and must lead to greater vigilance in these patients. - ] . eighteen patients ( %) survived at icu discharge with a good neurological outcome. by multivariate logistic regression analysis, female sex, initial shockable rhythm, and pre-ecmo arterial blood ph ≥ . were independent predictors of survival with good neurological outcome. all of the patients presenting with cpc score of or at icu discharge had a shockable rhythm and or ph ≥ . before ecls implantation. % of the patients presenting with these criteria had a good neurological outcome at icu discharge. all of the patients presenting with non-shockable rhythm and ph < . before ecls implantation died in the icu. conclusion: about one third of the patients presenting with shockable rhythm and or ph ≥ . before ecls implantation had a good neurological outcome at icu discharge. on the contrary, all of the patients presenting with both non-shockable rhythm and ph < . before ecls implantation died in the icu. these simple parameters might help to identify cardiac arrest patients which could benefit from ecls implantation. radjou aguila introduction: the decrease of lung volume is a keystone for the management of patients under mechanical ventilation in intensive care units. this procedure has not only led to a reduction of morbimortality in ards but also in all patients mechanicaly ventilated in intensive care units as well as in major surjery. nevertheless, the incidence of high volume (vt) on morbimortality is extremely variable (about to %). our main objective is to assess the incidence of high volume ventilation (> ml/kg predicted body weight, pbw) in our hospital intensive care units. moreover we were interested in determining the risk factors of high volume ventilation. we conducted a retrospective observational study from january to march in three intensive care units of a tertiary university hospital. all patients ventilated under sedation in vac mode during the h after admission were included in the study. of the patients admissions during the period, one of them ( %) have no height mentioned in their medical file and were exluded. among the patients considered, ( . %) were ventilated with high vt (fig. ). % of patients had a positive expiratory pressure ≥ cmh o. in multivariable analysis, height (smaller) and weight (lower) are the only associated factors with a high volume ventilation (p < . and p = . , respectively). discussion: the observed incidence on high vt patients is higher than that reported in most papers in literature (jaber et al. %, hess et al. %) . nevertheless, both studies were conducted in operating room with higher vt cut-off ( ml/kg). walkey and al showed that % of patients in ards were ventilated with vt › ml/kg of pbw. moreover, the same associated factors (smaller height and lower weight) have found in the study. older studies revealed higher bmi as factor to high volume ventilation. this difference could be explained by the use of predicted body weight. conclusion: although the growing literature and the recommandations aim to reduce the lung volume between to ml/kg of pbw, still one third of the patients in intensive care units are ventilated with too high lung volume. (fig. ). with either a nc overlap on one nostril or not. results: when the mv increases, the fio decreases. when the mouth opens, the fio decreases. when the prongs are overlapping one nostril the fio decreases slightly (mean ± % in absolute value). statistical differences were found between closed and open mouth and between overlap on one nostril and not (p < . ), except between tmo and cm at two mv ( and l/min) when nc overlap on one nostril (fig. ) . conclusion: when the prongs of nc are not correctly placed in the nostrils, the fio decreases, but this impact is limited in our bench study. the impact of mv increases and mouth opening on the fio values is also important. introduction: the weaning of mechanical ventilation is an essential and delicate phase in the management of a resuscitation patient. the neurosurgical patient presents a number of specific problems, such as impaired control ventilatory control, coughing or the pharyngo-laryngeal intersection. however, it often allows short-term ventilatory withdrawal in the neurosurgical patient, probably largely by the simple fact that it authorizes the definitive cessation of sedation. the objective of the study and demonstrate the place of tracheotomy in neuro-resuscitation patients, and prevent its complications. a retrospective descriptive study of patients hospitalized in the neuro-resuscitation unit during the period january to december , of which patients benefited from surgical tracheotomy, is a frequency of % of all inpatients during this period. clinical, para-clinical, etiological, and therapeutic data were collected from hospitalization records. in a series of hospitalized patients, during the defined period, patients had surgical tracheotomy, a frequency of %, in the literature two studies or the data were extremely variable, with % in the study namen versus . % in the coplin study. of the tracheotomies, were performed by neurosurgeons, and by resuscitators at a frequency of %. the tracheotomy was performed on average days after the intubation of the patients, after verification of the impossibility of the extubation of the latter either for central affection of the ventilatory controls, or reached the mixed nerves and disorders of the laryngo-pharyngeal intersection and according to expert recommendations in -tracheotomy should not be performed in the intensive care unit before the fourth day of mechanical ventilation. different pathologies that patients suffered and required tracheotomy were: post-operative complications of brain tumors (brain stem and mixed nerves) with patients, a rate of %, vascular pathologies (stroke and cvt)), with patients ( %), traumatic pathologies, with patients ( %). cases, %, cases of secondary bleeding of the orifice, cases of tracheal stenosis, and case of tracheomalacia. the decan made after pharyngolaryngeal neurological examination, and according to sfar recommendations experts suggest that a multidisciplinary decanulation protocol available in resuscitation departments. conclusion: tracheotomy in neuro-resuscitation has its place, especially in view of the different complications specific to this type of patient, but no study has demonstrated its improvement in vital prognosis. post-tracheotomy complications can be considerably reduced if the protocols and expert recommendations are applied. introduction: noninvasive ventilation (niv) in intensive care (icu) is associated with the occurrence of frequent asynchronies related to the leaks around the interface, mainly auto-triggering and delayed cycling. their detection requires a respiratory muscles activity monitoring. diaphragmatic ultrasonography is a simple imaging technique available at bedside to assess diaphragm motion. whether diaphragmatic ultrasonography would allow detecting asynchronies due to leaks during niv is unknown. the aim of this study was to assess two methods of diaphragmatic ultrasonography (excursion and thickening), coupled with the airway pressure signal to detect patient-ventilator asynchronies during niv. patients and methods: nine healthy subjects were placed under niv and subjected to intentional inspiratory and expiratory leakage on the ventilator circuit to generate delayed cycling and auto-triggering, respectively. the flow, airway pressure and diaphragmatic electromyogram were collected in order to identify the asynchronies generated by the leaks. in the meantime, an ultrasound recording of the excursion of the right diaphragm and of the thickening of the right diaphragmatic zone of apposition were performed and combined with the display of airway pressure on the ultrasound screen. these records were analyzed a posteriori to define the diagnostic performance [including sensitivity (se), specificity (spe), positive predictive value (ppv), and negative predictive value (npv)] of the excursion and the thickening to detect asynchronies. the experimental setup generated a median of asynchronies per subject (interquartile range - ). auto-triggering was correctly identified by continuous recording of both excursion (se = %, spe = %, ppv = %, and npv = %, fig. a ) and thickening (se = %, spe = %, ppv = %, npv = % + fig. c ). delayed cycling was detected with a slightly lower performance by diaphragm excursion (se = %, spe = %, ppv = %, npv = % + fig. b ) and thickening (se = %, spe = %, ppv = %, npv = % + fig d) . discussion: these encouraging results may be tempered by a variable effectiveness of the technique from one subject to another, in particular concerning the excursion. moreover, their generalization to critically ill patients may depend on several factors including echogenicity, stability and amplitude of the ultrasound signal in this population. conclusion: ultrasound is a simple clinical tool available at the bedside to detect delayed cycling and auto-triggering associated with niv leaks, provided that the airway pressure curve is displayed on the screen of the ultrasound machine. further studies are needed to assess its usefulness in detecting other types of asynchronies and its feasibility in critically-ill patients. introduction: although extra-corporeal co removal (ecco r) is not recommended, strong rational supports the concept. we aimed to describe our single-center experience of ecco r in the setting of mild to moderate acute respiratory distress syndrome (ards) and chronic obstructive pulmonary disease (copd). we performed a retrospective case note review of patients admitted to our tertiary regional intensive care unit (icu) and commenced on ecco r from november to august . demographic data, physiologic data (including ph and partial pressure of carbon dioxide in arterial blood [paco ]) before ecco r starting, and at day were recorded. results: twenty one patients received ecco r. thirteen were managed with hemolung ® device, seven with prismalung ® and one with ila ® . indication for ecco r were copd exacerbation (n = ), mild to moderate ards (n = ), uncontrolled hypercapnia due to pneumonia (n = ), and hypercapnia due to bronchial compression by mediastinal adenopathy (n = ). before starting ecco r, median minute ventilation, ph and paco were respectively . [ . , . conclusion: our observational cohort shows that ecco r therapy is effective to reduce paco and improve ph in the settings of mild ards and copd exacerbation. however, early weaning of sedation and pressure support ventilation might limit the decrease of respiratory rate and tidal volume. introduction: duchenne muscular dystrophy (dmd) is an x-linked recessive genetic disorder, caused by mutations in the dmd gene. respiratory failure is classical in the natural history of this disease. little is known about the diaphragm echographic pattern and the spectrum of patients with diaphragmatic paralysis in this disease. we aimed to assess the relationship between age and diaphragmatic motion and thickening fraction (tf) and to characterize the spectrum of patients with diaphragmatic paralysis. patients and methods: we included retrospectively dmd patients who experienced diaphragmatic echography and spirometry in our institution. diaphragmatic paralysis was defined as a diaphragm with tf < %. results: dmd patients were included in this study. all dmd patients were wheelchair bound. dmd patients had severe respiratory insufficiency with a median vc at % of predicted value [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . . % of patients were on home mechanical ventilation (hmv) and % were invasively ventilated. right diaphragmatic motion at deep inspiration was severely altered with a median of . mm [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . right tf of the diaphragm was severely altered with a median of . % [ . - . ] . . % of patients disclosed a paralyzed diaphragm pattern with a right tf < %. the age was inversely correlated with tf of the diaphragm (r = - . , p . ) and with the right diaphragm inspiration motion (r = − . p < . ). patients with diaphragm paralysis were older with median age at . years [ - . ], with severe respiratory impairment (median sitting cv = %) and median cumulated annual hmv duration at . years. conclusion: in dmd, age is inversely correlated with diaphragm function. diaphragm paralysis is frequent in older adult non-ambulant dmd. . the final probability model included the previous identified factors in addition to age and saps ii score, this model exhibited good calibration (hosmer-lemeshow x , p = . ) and good discrimination (roc-auc, . + % confidence interval, . - . ) (fig. ) . conclusion: our cohort study identified risk factors of icu death, mainly collected at admission among patients with aecopd. the proposed probability model has a good performance in predicting the short-term prognosis. further evaluation in other cohorts is needed. introduction: precarity is a complex notion including several components, and its definition is still debated. it is more subtle than financial poverty alone, and can increase population's health insecurity. we hypothesize that patients with precarity features may have different epidemiologic characteristics and icu outcomes than the general population. the aim of this study was to describe precarity features and outcomes of patients admitted to an icu located in a high poverty rate territory. patients and methods: we conducted a prospective single-center observational study of all patients admitted to icu of the saint-denis general hospital, from february to july . precarity features were classified in categories-absence of health insurance, lack of incomes or minimum allowances, homelessness or social home or hotel, and social isolation (no social link, or associations or neighbors). others social data were collected (speaking fluent french and education level) as well as usual clinical icu data. results: among patients included, precarity features were found in patients ( . %). income precarity was the most common, followed by accommodation precarity, health precarity and relation precarity (table ) . precarity was not associated with hospital mortality ( vs. . %, p = . ). all types of precarity were significantly associated with each other. precarious patients were younger ( vs. years-old, p < . ) and had less comorbidities. we found no differences concerning hospital or icu length of stay ( vs. days, p = . ) or concerning education level between precarious patients and the others. conclusion: our pilot study shows that precarity features are indeed very frequent and are often cumulated. with respect to the small patient sample, precarity does not seems to be associated with hospital mortality or length of stay. further investigations with larger patient samples and multicenter designs are warranted to investigate properly the impact of precarity on icu management and outcomes. introduction: population aging is a global and expanding phenomenon. elderly people are particularly vulnerable, and often need health care. this demographic evolution also affects intensive care units, and years old patient are now frequently admitted-it corresponds to % of admission in france. indeed we have analyzed the change in management of this very elderly people ( years old and more) over the past years in a french medical intensive care unit in a provincial university hospital. patients and methods: a retrospective cohort study was conducted using medical intensive care unit registry for demographic, physiological and diagnostic data from january to december . characteristics and treatment intensity during medical icu stay were specified, and short term and long term mortality were also recorded. results: a total of admissions, including octogenarians and older, were registered during the period. the proportion of very elderly people gradually increase from to %. intensity of treatment (organ support) increased from . from . per patient between the primary and the second part of the period, notably linked to mechanical ventilation ( vs. %, p < . ) and vasopressor infusion ( vs. %, p < . ). even if severity score increased (saps increase from . to . , p < . ), the icu mortality remains constant ( vs. . %). however, we were surprised to observe an increase in year mortality ( to %, p < . ). conclusion: between and , proportion of admission of very elderly people has increased two fold in our icu. although treatment intensity increases for more severe patients, icu mortality remains the same. nevertheless, absence of beneficial effect after year remains questioning. could icu to ward transfers and care course after hospital be optimized? lived alone at home, % in couple or with ther family, ( %) in retirement home and ( %) in nursing home. ( %) had a simplified ald score lower than indicating good functional independence. the more frequent diagnosis were acute pulmonary oedema and exacerbated copd. the mean simplified acute physiology score (saps ii) was ± . the treatment were were invasive mechanical ventilation ( %), only with noninvasive ventilation ( %), vasopressor agents ( %) and ( %) with renal replacement therapy. the average length of stay was . ± . days. after adjustment on sap-sii (without age), those invasive treatments were not associated with mortality no more than age. global mortality rate was %. ( %) were subject of a procedure for limiting therapeutics, among which ( %) died in the unit versus % for the other patients. the decision of therapeutic limitation was associated with severity of illness as measured by the sapsii (p = . ) but not with age. frequency of therapeutic limitation were similar in icu and intermediate care units. the mortality rate is lower than the older studies (s de rooij - %). unlike the study of p. biston ( ) which covers only the most serious cases, the mortality for any type of gravity remains reasonable. the procedure for limiting care were frequent especially for the most severe pathologies but all the patients who a decision of limiting care were stated were not dead. the patients over years old admit in french icu are very chosen. any major treatment appear to enhance mortality. introduction: due to advancements in medical technology and management of illnesses, an increasing proportion of critically ill patients are elderly. few information is available on the prognosis of these patients after icu discharge. the aim of this study was to analyze the clinical characteristics and long-term outcomes of elderly admitted to icu. patients and methods: monocentric, observational prospective study was performed. all elderly survivors (aged ≥ years) after an icu stay in a medical tunisian icu between january and december were included. data collected were: clinical features at admission, acute management procedures, functional characteristics and vital parameters (blood pressure, heart rate, abg's) at icu discharge. patients were followed during year via phone calls. a multivariate regression analysis was used to identify risk factors for one-year mortality. results: during the two-years study period, elderly patients were discharged alive. ( . %) were male. clinical features of elderly survivors were: mean age, . ± . years, median of charlson index, [ - ], chronic respiratory disease, ( . %), hypertension, ( . %) and diabetes ( . %). the most common reason for admission was acute respiratory failure in ( . %) patients and mean saps ii was . ± . . ( . %) patients required invasive ventilatory support, ( . %) vasoactive drugs and ( . %) received renal replacement therapy. the median of icu length of stay was days. the follow up was possible for ( . %) patients. mortality rate at year was . %. predictors of one-year fatal outcome in univariate analysis were as follows-saps ii (p = . ), heart rate at discharge (p = . ), decline in functional status (p = . ), world health organization (who) performance status at discharge (p = . ) and readmission within month (p = . ). multivariate regression showed that saps ii (or, . + % ci [ . - . ] + p = . ), who performance status at discharge (or, . + % ci [ . - . ] + p = . ) and heart rate (or, . + % ci [ . - . ] + p = . ) were independent risk factors of one-year mortality. conclusion: this study suggests that age and comorbidities should not be exclusion criteria for icu admission. in the long-term only saps ii, performance status and heart rate were significantly associated with one-year mortality in the elderly icu survivors. introduction: triage is an act performed at the entrance of emergency departments (ed's), it allows the classification of patients in different categories according to the seriousness and the priorities of treatment. vital emergencies are geared towards resuscitation room. in our ed, triage is not codified and is «done» in most cases by an unqualified staff. the aim of this work is to show the impact of absence of triage on the functionning of the resuscitation room. patients and methods: it's a prospective study, conducted in the ed of a university hospital, over months, including all patients over years old, admitted at the resuscitation room. epidemiological and clinical data of patients, their ccmu classification (classification clinique des malades aux urgences) have been specified, as well as their outcomes. we collected patients. the average age was . years old ( - years), for a sex ratio of . . forty patients ( . %) arrived «standing» at the ed. patients ccmu and represented . % of these admissions. the systolic blood pressure was under mmhg in % of cases, the glasgow coma scale < . in % of cases, and the spo < % in % of cases. mortality was . %. the other patients were admitted at the intensive care unit ( %), at the short stay hospitalization unit ( . %), at the operating room ( . %), or transferred to other departments ( . %). discussion: the patients ccmu and arrived by ambulance, «lying» , were considered as severe. the proximity of the resuscitation room of consultation rooms allows it to be used sometimes in flows' management and as a place of triage. the patients transferred straight to services didn't show signs of vital distress motiving their initial admission at resuscitation room or even at ed. those admitted at the short stay hospitalization unit were steady, but needed complementary examinations, specialized expert advice, or were waiting for a downstream bed. conclusion: a triage system must be introduced at the entrance of our emergency departments. the staff involved in that sorting must be identified, and disposing of a triage scale in order to figure out the degree of priority associated to patients conditions, and direct the ones needing urgent care towards the resuscitation room. results: one hundred patients were included, with average age of . years old ( - ) and sex ratio of . . these patients were brought to emergencies by their family in % of cases. reasons for admissions were varied, severe deterioration of their general condition ( %), alteration of consciousness ( %), respiratory distress ( %), convulsive seizures ( %). therapeutic interventions were cardio-pulmonary resuscitation ( %), fluid volume expansion ( %), mechanical ventilation ( %), administration of vasopressors ( %) and anticonvulsants ( %). mortality at the resuscitation room was %. thirty eight patients were admitted at the intensive care unit, equally at the short stay hospitalization unit (ssu) of ed. two patients returned home at the request of their family. discussion: these results show that ed's remain the last resort in front of oncology patient who is deteriorating, the occurrence of complications, and sometimes, the psychological exhaustion or family's obstinacy. emergencies departments continue admitting patients with terminal cancer, but are not organized for medium and long term care. the creation of a palliative care unit and the organization of home-based care will allow the prevention and treatment of complications as well as a psychological care, thus improving the living quality of these patients and their relatives. refusal of intensive care admission: assessment of a tunisian icu practices merhabene takoua introduction: need of intensive care exceeds its availability in several countries. as a consequence, rationing intensive care unit (icu) beds is common and often leads to admission refusal. purpose-to report refusal determinants and characteristics of patients associated with decisions to deny icu admission. this study was performed at the icu of abderrahman mami hospital, a -bed icu in ariana, tunisia. it was a prospective study enrolled between st january and th december . no predefined admission criteria were determined. decisions to admit are based on a combination of patient-related factors, severity of illness and bed availability. all consecutive patients referred for admission to icu during the study period were included. groups were defined gi-admitted patients and gii-refused patients. the reasons for refusal were categorized as follows: too well to benefit, too sick to benefit, patient or family refusal, necessity of other exploration not available in our institution and unit too busy. results: during the study period, icu admission was requested for patients of whom were admitted ( %). of the patients refused, only were admitted to icu later. refusal of icu admission came in % of cases from the emergency room and wards of our hospital, in % from other hospitals of whom % without icu. reasons of refusal were no beds availability ( . %), too sick to benefit from icu ( %), too well ( . %) and necessity of other exploration ( . %). no differences in demographic characteristic between the two groups were noted. among the refused patients, when compared with admitted patients, we found higher proportions of hematologic malignancies (p < . ) and cardiocirculatory arrest (p = . ). on the other hand, admitted patients were more likely to have cardio-respiratory comorbidities ( / vs. / , p = . ) and more need to mechanical ventilatory support ( vs. , p = . ). conclusion: our study confirms that icu refusal rate still high. it depends on both icu organization and patient characteristics. acute heart failure syndroms in intensive care: clinical features, management and outcome jamoussi amira , ajili achraf , merhebene takoua introduction: classification of acute heart failure (ahf) into clinical scenari (cs) was first proposed to facilitate early management ( ) . a decade after implementation of this approach, epidemiological and evolutive data based on this classification are interesting to investigate. that is why we aim to describe frequencies, management and mortality of each ahf syndrom in intensive care. a prospective study of patients > years with ahf admitted to the medical intensive care unit (icu) of abderrahmen mami hospital from january to august was conducted. patients were classified according to the clinical scenari ( ). clinical, therapeutic and outcome findings were recorded. results: during the study period ( months), we admitted patients in icu from whom ( . %) presented with ahf and then enrolled. the median age was of ± . years and sex-ratio . . a medical history of copd ( . %), hypertension ( . %), diabetes ( . %), ischemic cardiopathy ( %) and valvular cardiopathy ( . %) were noticed. at admission, severity assessement scores were: median apache ii . ± . and median saps ii ± . . clinical and evolutive characteristics according to clinical scenari are listed in table . conclusion: cs and cs are the most frequent ahf syndroms in icu and also have the best outcome. introduction: in cardiac arrest patients resuscitated from an ischemic ventricular fibrillation or tachycardia (vf/vt), both incidence and risk factors of recurrent severe arrhythmia are unclear. whether it is useful to give a prophylactic anti-arrhythmic (aa) treatment during the first hours and days is debated, particularly when a successful coronary reperfusion was provided. we aimed to evaluate the incidence of severe arrhythmia in patients resuscitated from an ischemic vf vt and to identify risk factors for developing arrhythmia during their icu stay. the procat registry captures all data from patients admitted in a tertiary hospital center after a resuscitated cardiac arrest (ca). we selected patients with an initial vf vt caused by an acute coronary syndrome (acs) and who were successfully treated with early percutaneous coronary intervention (pci) on admission. the primary endpoint was the recurrence of major arrhythmia between icu admission and icu discharge. all arrhythmias resulting in ca recurrence and or severe arterial hypotension requiring infusion of vasopressors were classified as major arrhythmias. multivariate logistic regression identified factors associated with the occurrence of major arrhythmias. results: between / and / , consecutive ca patients were included in the analysis. all patients underwent a successful pci of the infarct-related artery on hospital arrival. the only drug used as a prophylactic aa treatment was amiodarone, which was employed in / patients ( %). overall, / patients ( . %) had a major arrhythmia recurrence during their icu stay. a large majority of these major arrhythmia recurrences ( . %) occurred during the first h. characteristics of patients with and without major arrhythmia recurrence are described in the table . in multivariate analysis, public place location (or . [ . - . ], p = . ) and male gender (or . [ . - . ], p = . ) were both associated with a lower risk of major arrhythmia recurrence during the icu stay. prophylactic aa treatment was not associated with a lower risk of recurrences of major arrhythmias (or . [ . - . ], p = . ). conclusion: despite an early coronary reperfusion, more than % of our post-cardiac arrest patients experienced a recurrent severe arrhythmia during the post-resuscitation period, mostly during the first h in the icu. this proportion is much higher than what is reported in common acute coronary syndrome (without cardiac arrest) and further studies are needed to explore protective strategies. introduction: during symptomatic treatment of septic shock, markers of anaerobic metabolism may be used in a goal-oriented strategy. the recent international guidelines for management of sepsis and septic shock suggested guiding resuscitation to normalize lactate as a marker of tissue hypoperfusion. the purpose of this study was to evaluate the kinetics of lactate and other markers during the first three hours and to compare their levels between survivors and non survivors. we conducted a prospective, observational, single-center study of patients admitted to a general icu from the may to august . inclusion criteria were patients age ≥ , intubated and under mechanical ventilation with septic shock as defined by the third international consensus conference. simultaneous sampling of arterial and central venous blood gas were collected at h and h to obtain lactate (mmol/l), and scvo (%). delta pco (mmhg) and delta pco /cavo (mmhg/ml) were computed by our patient data management system and presented as a chart with additional hemodynamic data for clinical decision support. comparisons of values between groups were made by mann-whitney u test as appropriate. p < . was considered statistically significant. all reported p values are two-sided. statistical analysis was performed using systat ver. . . results: we studied intubated septic shock patients aged ± years, saps ii ± , sofa ± . . community pneumonia and peritonitis were the major sources of infection. icu mortality rate was %. all patients received norepinephrine ( . ± . µg/kg/ min), two patients received dobutamine ( . ± . µg/kg/min). the evolution of markers is summarized in table . at h and h , arterial lactate levels were higher in non-survivors than in survivors, but did not decrease at h in both groups. at h there was no statistical difference concerning scvo , delta pco and delta pco /cavo . after three hours of resuscitation, delta pco and delta pco /cavo ratio decreased and scvo increased in survivors. survivors had lower delta pco and delta pco /cavo ratio than non survivors. conclusion: although high lactate level is a key signal of anaerobic metabolism, it did not decrease during the first three hours in this group of severe septic shock patients. instead of using lactate, delta pco and delta pco /cavo kinetics could be integrated in a goaloriented strategy for septic shock resuscitation. introduction: to assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by oesophageal doppler (cidoppler). patients and methods: in patients, before infusing ml of saline, we measured cidoppler before and during the last seconds of successive -second end-inspiratory occlusion (eio) and endexpiratory occlusion (eeo), separated by min. patients in whom volume expansion increased cardiac index (transpulmonary thermodilution) > % were defined as "fluid responders". results: eeo increased cidoppler more in responders than in nonresponders ( ± vs. ± %, respectively, p < . ) and eio decreased cidoppler more in responders than in non-responders (- ± vs. - ± %, respectively, p = . ). thus, when adding the absolute values of changes in ci observed during both occlusions, cidoppler changed by ± % in responders and ± % in nonresponders. fluid responsiveness was predicted by the eeo-induced change in cidoppler with an area under the receiver operating characteristic (roc) curve of . ( % confidence interval- . - . ) and a threshold value of % increase in cidoppler. it was predicted by the sum of absolute values of changes in cidoppler during both occlusions with a similar area under the roc curve ( . ( . - . )) and with a threshold of % change in cidoppler, which is more compatible with oesophageal doppler precision. in this case, the sensitivity was ( - )% and the specificity was ( - )%. conclusion: if consecutive eio and eeo change cidoppler > % in total, it is very likely that volume expansion will be efficient in terms of cardiac output. the measurement of cardiac output using a signal morphology-based form of impedance cardiography (physioflow ® ) in intensive care unit: comparison with the trans thoracic echocardiography. introduction: in the intensive care units, the cardiac output (co) is one of the main hemodynamic parameters required to manage patients in shock. the physioflow ® is a new non-invasive method using the waveform analysis of the thoracic impedance signal (ti) to assess co. in hemodynamicaly unstable patients, no studies have evaluated the level of agreement between the co estimated by transthoracic echocardiography (co-tte) and that measured using the waveform analysis of thoracic impedance physioflow ® (co-ti). the objective of this study was to evaluate the ability of co-ti relative to co-tte to estimate the absolute co value and detect the expected variation co (v-co) in critically ill patients. patients and methods: fourteen patients sedated and mechanically ventilated, in shock under catecholamines and monitorred with tte and ti physioflow ® were included. hemodynamic datas, stroke volume (sv) and co with two monitoring were performed at baseline min before passive leg raising (plr), s after plr and min after volume expansion (ve) of ml of saline solution. responders were defined by an increase > % of cardiac output (v-co) after plr. results: fourteen pairs of tte and ti measurements were compared. the median (iqr) age was years ( - ), igs was ( - ). only patients were responders after plr. there was a significant correlation between the co-tte and co-ti measurements (r = . , p < . ). the median bias was . l/min and the limits of agreement (loas) were − . and . l/min. there was a significant correlation between v-co-tte and v-co-ti (r = . , p = . ) (fig. ) . the median bias was- . % and the loas for v-co were respectively - . and + . %. conclusion: the co measured with physioflow ® , a signal morphology-based impedance cardiography, is correlated to the co measured with tte. however, the high loa observed in this preliminary study underline the necessity to remain careful and wait for further inclusions. - ] vs. . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days, p = . ). despite imbalancedunderlying characteristics in terms of demographics and comorbidities, in-icu mortality rates were similar between patients ( . vs. %, p = . ). conclusion: prior bb treatment have limited impact on the severity of acute circulatory failure in septic shock and is not associated with increased mortality despite the underlying frailty of patients. introduction: cardiac output monitoring is a key component in the management of critically ill patients. cardiac output estimated by transthoracic echocardiography is documented in patient with atrial fibrillation, but a large part of transpulmonary thermodilution validation studies excluded this specific population. the objective of this study was to evaluate cardiac output mesurement and trend ability by transpulmonary thermodilution relative to transthoracic echocardiography in critically ill mechanically ventilated patients with atrial fibrillation. patients and methods: thirty mechanically ventilated patients requiring hemodynamic assessment were included in a prospective observational study. cardiac output was mesured simultaneously with transpulmonary thermodilution and transthoracic echocardiography. seventy-four pairs of cardiac output measurements were compared. the two measurements were significantly correlated (r = . et p < . ). the mean bias was - . l/min, the limits of agreement were - . and + . l/min, and the percentage error was . %. thirty-four pairs of cardiac output variation measurements were compared. there was no significant correlation between cardiac output variation measurements by transpulmonary thermodilution and transthoracic echocardiography. the mean bias was − . l/ min and the limits of agreement were − . and + . l/min. with a % exclusion zone, the four-quadrant plot had a concordance rate of . %. the polar plot had a mean polar angle of . ° with % confidence interval between − . ° and . °. conclusion: in critically ill mechanically ventilated patients with atrial fibrillation, cardiac output measurements with transpulmonary thermodilution and transthoracic echocardiography are not interchangeable. introduction: basic critical care echocardiography (cce) relies on transthoracic echocardiography (tte). we sought to assess the diagnostic capacity of a next-generation micro-digital broadband beamformer in patients with cardiopulmonary compromise. all patients with acute circulatory respiratory failure underwent two basic tte assessments using successively a next-generation micro-digital broadband beamformer ( elements, - mhz) incorporated in a sector phased array probe with twodimensional, m-mode and color doppler mapping capacities which was connected to a touchscreen interface (lumify, philips), and using a compact full-feature imaging system ( elements, - mhz + cx , philips). tte examinations were independently performed in random order by two intensivists with expertise in cce, within a -min time frame without therapeutic intervention. imaging quality was graded from (no image in the corresponding view) to (clear identification of % of endocardial boarders). the concordance of qualitative data was assessed using the kappa test and agreement of two-dimensional measurements (left ventricular end-diastolic diameter [lvedd], ratio of right ventricular (rv) and lv end-diastolic diameters [rvedd lvedd] + end-expiratory inferior vena cava diameter [dexpivc]) was evaluated using intraclass coefficient correlation (icc). results: thirty consecutive patients were studied, without any exclusion for absence of tte images (age, ± years, sap-sii, ± , % ventilated, % under catecholamines, lactate, . ± . mmol l). the proportion of echocardiographic views eligible for interpretation and mean duration of tte examinations were similar with the miniaturized and full-feature systems ( vs. %, . ± . vs. . ± . min, p = . ). two-dimensional imaging quality grade was lower with the miniaturized system ( system. concordance of two-dimensional measurements was also good-to-excellent (table ) . conclusion: for basic cce use, next-generation micro-digital broadband beamformer appears providing reliable information with good-to-excellent diagnostic capability, accurate two-dimensional measurements, and adapted therapeutic suggestions. these preliminary data require further confirmation. introduction: acute kidney injury (aki) in very old patients (over years) admitted in intensive care unit (icu) is a frequent issue and is known to be associated with a severe prognosis. we aimed at describing the clinical characteristics and prognosis of such a population. the objective of the study was dual: first to evaluate the short and long term mortality of these patients, second to determine the factors associated with a poor outcome. patients and methods: we conducted a descriptive, retrospective and monocentric study based on the hospital records of patients over years with aki admitted in our icu between january and december . the patients were selected according to the kdigo criteria ( ) . survivals at the discharge from hospital, at day and at year were assessed. the factors associated with mortality at year were scrutinized. results: after excluding patients for an initial therapeutic limitation, the data of remaining patients were reviewed. the patients were years old (interquartile range, iqr - ) and were predominantly male gender ( %). saps ii and sofa score at admission were (iqr - ) and (iqr - ) respectively. % of the patients needed for mechanical ventilation and % of them needed for catecholamine use. septic ( %), prerenal ( %), iatrogenic ( %) and cardiogenic injury ( %) were the leading cause of aki. dialysis was performed in % of patients. the overall mortality at the discharge from icu, at day and at year was , and % respectively (fig. ) . neither were the age, the comorbidities, the etiology of aki nor the need for dialysis associated to a significant increase in mortality. a stepwise cox regression analysis revealed saps ii and blood lactate level at icu admission as independent risk factors associated with year mortality. conclusion: aki at admission in icu is associated with a high mortality at year in an elderly population. main long term prognostic factors are linked to the initial severity at icu admission. introduction: the proportion of elderly around the world doesn't stop growing and increases the consumption in health care. however, lots of studies report the impact of the age on the decision to admit a patient to the icu despite no triage recommendation exists. the primary objective was to determine prognostic factors of death for the years and over at admission to the icu and secondly to evaluate their functional prognostic at short and medium term after their exit. patients and methods: prospective and observational study conducted in our icu beds unit from august to february . patients of years and over were listed. the dying patients arriving after a pre-hospital resuscitation for whom no therapeutic plan has been initiated and those admitted for an organ donation were excluded. the primary outcome was the duration between the admission and the potential death during the follow-up. the secondary outcomes were the necessity to entry an healthcare institution or the loss of one autonomy point on the adl french scale after the hospitalization. results: patients of the admissions were included. the igs ii and sofa average scores were respectively . ± . and . ± . . the most common diagnosis were a septic shock ( patients), a cardiopulmonary arrest ( patients), a cardiogenic shock ( patients) and a pulmonary oedema or a lung infection ( patients fig. survival of very old patients with aki in icu (%) each). patients ( . %) died during the follow up- at the icu, during ward and during re-education or after their home return. from a multivariate analysis (table ) , anisocoria, cardiopulmonary arrest and acute kidney injury (aki > ) seem to be independent risk factors of death. patients were alive at the end of the follow up. recovered their previous autonomy, needed a place in a specialized institution. all the other lost a part of autonomy months after their home return with the average loss of one point on the adl autonomy french scale. conclusion: anisocoria, aki and cardiopulmonary arrest seem to be independent risk factors of death for those patients. concerning the survivors, a stay at the icu lead to an increased dependency. other studies have to be led to evaluate which of our patients could have get the best benefit of their stay to prevent from a misuse of the structure. introduction: context-among the severe complications of preeclampsia, acute kidney injury (aki) poses a dilemma if features of thrombotic microangiopathy (tma) are present. although a hellp syndrome is considerably more frequent, ruling out a flare of atypical haemolytic and uremic syndrome (hus) is then of utmost importance. objective-to improve the differential diagnosis procedure in cases of post-partum aki. patients and methods: a hundred and five cases of post-partum aki, admitted in the last years ( ) ( ) ( ) ( ) ( ) in french icu from different regions, were analysed. initial and final diagnosis, renal features, haemostasis and tma parameters were all analysed, paying a special attention to their dynamics within the first days following the delivery. results: the main circumstances of aki were severe preeclampsia (n = ), post-partum haemorrhage (pph, n = ) and primitive tma (n = , including atypical hus and thrombotic thrombocytopenic purpura). among the thirteen cases of renal cortical necrosis, were associated with preeclampsia. congruence between the initial and the final diagnosis was low ( %). thus, none of the women referred to our centers for a suspicion of non-placental tma has received a final diagnosis of non-placental tma (and instead had a pe or a pph). conversely, all women with a final diagnosis of nonplacental tma were referred for a suspicion of pe-related tma, or with a pph which polluted the diagnosis. tranexamic acid was largely used in the context of pph ( %), at a dose up to grams total. taking into account the final diagnosis, we subjectively concluded that plasma exchanges and eculizumab were abusively indicated in and cases, respectively, of typical hellp syndrome. plasma exchanges were in itiated in all cases, a mean h following the admission. dynamics of hemoglobin, haptoglobin, and liver enzymes were poorly discriminant. the dynamic pattern of ldh and of platelets, in contrast, was statistically different between primitive tma-related aki and other groups-at day , platelets increased in preeclamptic women, and in other circumstances, but not in patients with primitive tma. a classification and regression tree (cart) independently confirmed the usefulness of platelets and ldh trajectory in the diagnostic algorithm (fig. ) . conclusion: the trajectory of ldh and platelet count is useful to identify the cause of post-partum aki, and the clinician may reasonably take therapeutic decisions at day post-delivery. introduction: continuous veno-venous hemofiltration (cvvhf) is a common practice in intensive care units (icu). because it is continuous, the choice of anticoagulation is essential-regional anticoagulation fig. analysis of post-partum aki cases with citrate or systemic with unfractionned heparin or low molecular weight heparin (lmwh). filter's lifespan is a major issue regarding filtration's effectiveness and cost. in this study, we compared the filter's lifespan between lmwh and citrate anticoagulation. patients and methods: a monocentric retrospective study was led from january to october . all the cvvhf sessions during this period were included. prismaflex© monitors (hospal) were used. practioners were free to choose between citrate or lmwh defining groups. we aimed a post filter ionized calcemia between . to . mmol/l in citrate group + and a post filter anti xa activity between . to . ui/ml in lmwh. results: cvvhf sessions were included- with lmwh anticoagulation, and with citrate. patients were years old on average, primarly males ( %), with an initial average saps ii score of . icu mortality was %. patients' hemostasis was measured before each cvvhf session, without any significant difference between the groups. global filter's lifespan was h + h in citrate group versus h in lmwh, without significant difference (p = . ) (fig. ) . no serious side effect, especially hemorrhage in the lmwh group, was reported. filtration efficiency, represented by the urea reduction ratio during the first cvvhf session, was similar, % ± % in lmwh group versus % ± % in citrate group (p = . ). conclusion: both anticoagulation-systemic with lmwh or regional with citrate can be used in icu. both methods enable long and comparable filter lifespan, with similar filtration efficiency and without serious adverse events. our results need to be confirmed by a randomized propective study. introduction: arf during the post-partum period is a rare complication. the main etiologies are post-partum haemorrhage (pph) and thrombotic microangiopathy (tma). rrt may be required. the aim of this study was to identify variables associated with rrt in this population admitted in icu. patients and methods: we conducted a study using retrospectively collected data in a cohort of patient with post-partum arf according to the kdigo criteria and requiring icu in the university hospital of lille from until . two groups were compared-rrt and non rrt patients. demographic and obstetrical data as well as data during icu stay and patients' outcome were collected. etiologies of arf, kdigo stage, anuria, hemolysis parameters and biological data at icu admission were studied. comparisons were made using a chi-two or fisher exact test or a mann-whitney u test. odds ratio (or) for the statistically different criteria were studied. results: twenty-two patients requiring rrt were compared to the patients without rrt. the two main etiologies of arf were tma ( . %) and pph ( . %). vaginal delivery was significantly more frequent in the rrt group compared with caesarian delivery (p = . ). use of rtt was significantly increased after pph compared the others etiology of arf (p = . ). in the rrt group, the icu length of stay was longer (p < . ) and igs ii score was higher (p < . ). higher kdigo score was observed in rrt patients (in the rrt group-kdigo = , = %, = %, and without rrt-kdigo = . %, = %, = %, p < . ). anuria h after icu admission was more frequent in cases of rtt ( . % versus . %, p < . ). hemolysis was greater in rrt patients with lower haptoglobin (p = . ) and increased lactate deshydrogenase (ldh) (p = . ). the association with rrt requirement was stronger with the duration of anuria, with an or at h at . [ . - . ] and at h at . [ . - ] . a lower haptoglobin was associated with a higher risk of rtt (or . [ . - . ]), as well as pph (or . [ . - . ] ) and vaginal delivery (or . [ . - . ]). conclusion: hemolysis parameters and anuria seemed useful criteria to identify patients at higher risk of rrt early during their icu admission. introduction: renal replacement therapy (rrt) has three aimsrestoring homeostasis, ensuring survival and preserving the potential for renal recovery. the main indication of rrt in icu is acute renal failure, correlated with a very important rate of mortality despite the progress made in its management. patients and methods: the objective of this work is to take stock of the indications and the objectives of the rrt in icu. through a prospective study, we report a serie of cases, collected at the multipurpose resuscitation unit of the avicenna military hospital in marrakech between september and september . results: the average age of our patients is , ± , years with extremes ranging from to years and a male predominance ( %). the main reasons for admission were hemodynamic distress in . % of cases, followed by septic shock in . % of cases, neurological and respiratory distress were noted in . and . % of cases, respectively. rrt indications were severe acidosis in % of patients, followed by % hyperkalaemia, acute pulmonary edema in %, hemodynamic instability in patients with chronic renal failure in %, acute renal failure in %, and hyperuriaemia in % of cases. the technique chosen is conventional intermittent hemodialysis with a synthetic membrane. the main duration of the sessions was h min ± mn. vascular access was a right internal jugular catheter in . % of patients and left in . %, right femoral catheter in . % of patients and left in . %, arteriovenous fistula (fav) and a tunneled catheter in . and . % of patients. mortality was , %, chronicity progressed in . % of cases and total or partial recovery of normal renal function in % of cases. conclusion: we have a high rate of mortality in our icu that's why we will focus on prevention of risk of renal failure in our patients. introduction: there is limited information on the outcome of acute kidney injury (aki) in patients with traumatic intracranial hemorrhage (tich). tich patient with aki was related high mortality rate. the aim of this study is to estimate the outcome using different renal replacement therapy on the survival rate and rate of long term renal-replacement therapy in adult tich patient. patients and methods: we retrospectively identified a total of tich patients with aki who required glycerol or mannitol therapy admitted to the intensive care unit during a -year period ending dec from the national health insurance research database. demographic data, severity of tich, medication, level of care, type of head surgery were collected. all patients subjects were older than > years. we also excluded patients diagnosed with tich before the cohort entry date, hemodialysis before tich, chronic kidney disease cancer coagulation defects purpura and other hemorrhagic conditions, mortality mechanical ventilation ischemic heart disease before tracking. the primary outcome was overall survival at day . the secondary outcome was the rate of long term hd therapy. results: a total of patients were enrolled. the kaplan-meier estimates of mortality at day did not differ significantly between the continuous veno-venous hemofiltration (cvvh) and hemodialysis (hd) strategies + deaths occurred among patients receiving cvvh-strategy group and deaths occurred among patients receiving hd-strategy group (adjusted hazard ratio: . , % ci . to . ; p = . ). the rate of long term hd was higher in the hd-strategy group than in the cvvh-strategy group ( . vs. . %, p = . ) especially in injury severity score ≥ group (table ) . discussion: in our study, tich patient with aki receving cvvh may have effect on renal blood flow protection or cytokine removal which lower the rate of long term hd. conclusion: these clinical data provides readers interventions to improve outcomes in this population and future study are needed to confirm the result. this study highlights the importance different renal replecement therapy in the tich with aki population (table ) . khaleq khalid , hattabi khalid , bensardi fatima zahra , bouhouri m. a , nciri a , hamoudi d , alharrar r introduction: the combined progress of abdominal surgery and anesthesia lead to more frequent surgical indications, including for fragile patients or serious pathologiespostoperative morbidity and mortality is an element that requires evaluation and analysis in surgical resuscitation. although pathological processes and new therapeutic approaches in surgery are currently well known, data on risk factors for morbidity and mortality are less available. the aim of our work is to evaluate the post-operative morbidity and mortality rate and to identify the main predictive factors. patients and methods: a retrospective-cohort, unicentric study that included all consecutive patients hospitalized in the surgical resuscitation department after abdominal surgery regardless of the operated organ, during years. the structured sheet of data collection included more than items on all perioperative data concerning the patient, the disease, and the operating surgeons. postoperative mortality and morbidity were defined as in-hospital death and complications. a first descriptive analysis of the various parameters collected was carried out a bivariate analysis was then performed to study the factors affecting morbidity and mortality in digestive surgery the comparison was made using the student's t test for quantitative variables and the chi square for the qualitative variables. a difference is considered significant when p < . ( %). results: among patients, the in-hospital death rate was . % and the overall morbidity rate was . %, the mean age was . ± , years with extreme ages of years and years with sex ratio of . . five factors were incriminated in post: operative mortality notably:renal failure p = . , duration of stay p = . , parenteral nutrition p = . , long duration of intubation p = . , perioperative blood transfusion p = . . three factors influencing morbidity were found: duration of stay p = . , parenteral nutrition p = . , long duration of intubation p = . . conclusion: knowledge of the true frequency of both mortality and morbidity is crucial in planning health care and research and identifying risk factors. introduction: tools to quantify and assess bowl management in critically ill are still very limited and often over-looked. with the primary fig. filter's lifespan concern of optimizing patients to preserve life, the problem of bowel care has been given less priority. the aim of this study was to use ultrasonographic measurements of gastric emptying in the critically ill as a tool of measurement of the impact of different specific factors of icu stay on bowl emptying. patients and methods: this is a prospective study conducted in an intensive care unit for months. it included patients. ultrasonic imaging of antral sections was undertaken every min for the first h and every min thereafter until total emptying. correlation analyses were calculated, applying an adjusted significance level (pb < . ) to correct for multiple testing. results: all our patients were above the age of . the median of age was years old . of our patients were male and were female. the total emptying median time was ± min. significant correlation was observed between length of stay and delay in bowl emptying. mechanical ventilation had also significant relation with slower bowl progression and gastric emptying. patients in septic shock had tendencies to earlier delayed bowl emptying compare to others patients included in our study. conclusion: the study we conducted is a pilot study. further studies should be conducted and unltrasonografic gastric assessment could be standardized in protocols to assess clinical decision making and improve nutrition and bowl management in icu patients. introduction: enteral nutrition, via a feeding tube, is often used in intensive care units (icu) to supply artificial nutrition to critically ill patients. the feeding tube is also commonly used to administrate drug therapy as well. however, there is a lack of knowledge of the nurses about this way of administration. this could be a potential source of medicine-related illness. the purpose of this study was first, to evaluate the nurse's knowledge on enteral drug administration, and second, to observe nurses and to evaluate the adequacy of their practices with guidelines, and to report medication-administration errors. patients and methods: this prospective study using the observation technique was conducted in icu (one medical and one surgical). first, a knowledge and practice questionnaire regarding drug administration trough enteral feeding tube was filled by each intensivist nurse. secondly, pharmacist performed observations of nurses during preparation and administration of medications. these practices were compared with the original medical prescription and with the data available in the literature. results: questionnaires were returned. nurses evaluated their knowledge as medium and as inadequate. there was a lack of knowledge on the type of drugs which can be used by feeding tube ( wrong responses). nurses and different drugs were observed during the drug administration phase. no administration totally complied with our institutional protocol, particularly the crush of tablets. when a tablet was crushed, in % an alternative formulation (in syrup for example) existed. the correct administration of drugs in feeding tubes is important and represents a challenge in icu. firstly, crushed tablets is the most frequent cause of obstruction of feeding tubes which have to be changed + secondly, crushed tablets destroys the controlled release of enteric coated dosage forms, resulting in a higher or a lower initial blood level. we have to train nurses for drug administration by feeding tube. on their daily ward, the pharmacist should improve the choice of medication's forms. introduction: acute variceal hemorrhage (avh) is a severe complication of portal hypertension. in addition, the variceal bleeding is still the most common lethal complication of cirrhosis. the most effective modality of treating is based on resuscitation combined with the endoscopic variceal band ligation. the purpose of this preliminary study was to find the factors associated with poor prognosis of avh in cirrhotic patients. patients and methods: this is a retrospective study, spread over months between january and december . are included all consecutive patients with liver cirrhosis hospitalized for variceal bleeding. we exploited the medical records to identify the clinical, biological and endoscopic parameters. results: a total of patients hospitalized for avh occurred during the study period. the mean age at admission was years, and are female. cirrhosis was post viral in % of cases. patients were classified as child-pugh c in % of cases. the median presenting model for end stage liver disease (meld) and clif sofa were respectively and . . twelve ( ) patients received beta-blockers and have required at least one endoscopic variceal band ligation at the time of the bleeding episode. in the acute phase, pharmacological treatment based on vasopressor (sandostatin)) was instituted in all cases and combining with antibiotic prophylaxis (c g or fluoroquinolone) in cases. in cases the endoscopy was made within h, active bleeding at endoscopy was observed in patients. esophageal avarices (ov) were grade i ( patients) grade ii ( patients) and grade iii ( patients). the eradication of varices was obtained in patients ( . % percentage of the cases). the variceal bleeding recurred in of patients ( %of cases) and patients died which within the first days. spontaneous bacterial peritonitis (p . ), hepatic encephalopathy (p . ) and the hemodynamic instability with schok (p . ) are correlated with early mortality at days. hepatic encephalopathy (p . ) and bacteremia (p . ) are corrolated with week motality. non selective betablocker (p . ) and primary use of band ligation when indicated (p . ) are protective factors and parameters of good outcome. conclusion: despite developing of endoscopic tools and respect of actual therapeutic guidelines in avh, the outcome is still poor. the prognosis appears to be dependent on the clinical condition at admission and primary prevention. introduction: the french intestinal stroke center based on a multimodal and multidisciplinary management has been developed to improve survival and intestinal viability. open surgical revascularization was decided for patients unsuitable for radiological revascularization and or suspected of intestinal necrosis. we aimed to study the prognosis of patients suffering from aoami in icu and who have benefited from open revascularization. single-center, observational and prospective study was carried out in a surgical icu of a tertiary center. patients with aoami managed in our intestinal stroke center from to and who underwent open revascularization were included. results: data of patients were collected. patients' characteristics are described in table . all patients had abdominal computed tomography angiography at the diagnosis, and patients ( %) presented signs of intestinal injury. thrombosis was the main mechanism of superior mesenteric artery (sma) occlusion ( patients, %). all patients received antiplatelet therapy, curative unfractionated heparin therapy and digestive decontamination. open revascularization was performed by sma endarterectomy ( patients, %), sma surgical bypass ( patients, %), retrograde open mesenteric stenting ( patients, %) and coeliac artery bypass ( patients, %). three patients ( %) underwent a radiologic endovascular revascularization attempt before open repair. small bowel resection ( cm ) was achieved in patients ( %). four patients ( %) had peritonitis. six patients ( %) had one or more relaparotomy ]), usually for hemodynamic instability ( %). only one patient died in icu ( %). icu lenght of stay was days ] and duration of mechanical ventilation was days [iqr - ]. overall, haemodynamic failure was present in patients ( %). median duration of vasoactive support was days [iqr - ]). severe acute respiratory distress syndrome was observed in patients ( %) and acute kidney injury in patients ( %, including patients who received renal-replacement therapy, %). enteral feeding was initiated in patients ( %) with a delay of . days [ . parenteral nutrition was administered in patients ( %), including patients ( %) without enteral feeding. five patients ( %) were discharged with small bowel syndrome. conclusion: icu patients who underwent open revascularization to treat aoami as part of a multimodal and multidisciplinary management in a dedicated intestinal stroke center have low mortality and intestinal resection rates. larger studies are needed to confirm these results. introduction: precise consequences of late transit in icu remain elusive. we have previously shown that defining late transit by the absence of stool within days after admission was not relevant because it did not identify a group of patients with specific outcome [ ] . to further improve this definition, we investigated the differences in outcome among patients according to their bowel movements frequency. patients and methods: preliminary results of a prospective, two centers, observational study. all patients admitted to icu, with a length of stay (los) of at least h were eligible and included with the following exceptions-abdominal surgery, bowel infection or any baseline condition known to alter transit time. patients were compared according to stool frequency-less than %, between and %, between and % or more than % of icu days. we also tested the former constipation definition of more than days after admission without stool passage. we registered demographic data, time spent under mechanical ventilation (mv), icu los, ventilation associated pneumoniae (vap) and vital status at discharge. results: over months, patients were screened and ( . %) were included, age . ± . years, mean saps ii ± , ( . %) mechanically ventilated. the most frequent exclusion criteria were los < h (n = ). % of the patients had stool less than % of icu days. patients with fewer bowel movements were more likely to be mechanically ventilated, without association with time spent under mv. there was a link between the time to first stool after admission and the stool frequency during icu (p < . vap n(%) ( . ) ( . ) ( . ) ( . ) death n(%) ( . ) ( . ) ( . ) ( . ) discussion: this study is limited by the number of patients leading to an imbalance between subgroups therefore limiting the comparison. conclusion: these preliminary results do not plead for an improvement of the late transit definition based on the frequency of stool. further data is warranted to better define this condition, and the management to provide. introduction: antibiotic therapy during acute exacerbation of copd (aecopd) still controversial and not well supported by clinical evidence. in fact half of these episodes are caused by viruses even during severe episodes with need to ventilator support. procalcitonin is effective to guide antibiotic therapy during acute exacerbation of copd without compromising patients' outcome, its efficacy in the intensive care setting still not well evaluated. we have conducted in a bed icu a before after study. during the first period (january -december ) patients with aecopd were included retrospectively and treated with antibiotics according to anthonisen criteria (control group). in the second period (january -may ) antibiotics were prescribed only if the procalcitonin level was greater than . ng ml (procalcitonin group). results: ninety-two patients were included, in the procalcitonin group and in the control group. antibiotics were administered at icu admission in patients ( %) in the procalcitonin group and in ( %) patients in the control group, p = . . only % of sputum cultures were positive at icu admission. time to recovery was similar between the two groups [ iqr ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , iqr ( - ), p = . ]. other patients' outcomes did not differ between the control group and the procalcitonin group with respectively: the mortality ( . vs. %, p = . ), the incidence of pavm ( vs. %, p = . ) and niv failure ( vs. %, p = . ). readmission to the hospital at day was significantly higher in the control group ( vs. %, p = . ). conclusion: using procalcitonin to guide antibiotic therapy during severe aecopd can reduce the use of antibiotics without compromising patients' outcomes. our study aimed to assess whether arc impacts negatively on cefazolin pharmacokinetic pharmacodynamics (pk/pd) target attainment and clinical outcome in critically ill patients. patients and methods: over an -month period, all critically ill patients treated by cefazolin for a documented respiratory infection without renal impairment were eligible. patients who underwent an empiric antimicrobial treatment > h before introduction of cefazolin were not included. during the first three days of antimicrobial therapy, every patient underwent -hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at steady state. the main outcome investigated in this study was the rate of pk pd target non-attainment defined by an unbound concentration < µg ml (mic value for inoculum > ufc ml). the secondary outcome was the rate of therapeutic failure, defined as an impaired clinical response with a need for escalating antibiotics during treatment and or within days after end-of-treatment. results: over the study period, patients were included ( samples analyzed for therapeutic drug monitoring). in pharmacological analysis, the rate of pk pd target non-attainment was %, with a strong association with crcl (p = . ) ( table ). in clinical analysis, the rate of therapeutic failure was % ( ), with a strong association with inoculum effect (p = . ). there was a strong association between therapeutic failure, crcl > ml min and pk pd target non-attainment adjusted on the inoculum effect (p = . ). introduction: vancomycin has long been used as the standard therapy of infections due to methicillin-resistant staphylococcus aureus (mrsa). the side effects of this drug as well as the increasing resistance and its pharmacodynamics effects have fostered the development of newly active drugs. nevertheless it is still widely prescribed and it stands as the mostly used comparator in randomized study. an assessment of our medical practice regarding its use may enhance compliance to guidelines so as to promote a better use of vancomycin. patients and methods: in our bed hospital, the incidence rate of mrsa fell from . to . per patient days from to whereas the current proportion of mrsa isolates is about %. vancomycin is the most prescribed empirical or targeted antibiotic therapy covering mrsa in our medical intensive care unit of beds even if a shift towards the use of linezolid in nosocomial pneumoniae has been noticed during the last years. key points regarding the proper use of vancomycin have been implemented in our antibiotic stewardship program. moreover courses concerning this topic are provided to our junior doctors. a retrospective review of the quality of antibiotic use has been carried out in courses of vancomycin therapy and the following criteria have been assessed-indication, dosing schedules, serum levels of vancomycin, duration of antibiotic therapy and the overall degree of conformity of the prescription. results: regarding indication, conformity was observed in cases ( %). the dosing schedule was appropriate in cases ( %) only. of the remaining cases ( %), all of them were not adjusted to the serum concentration and in cases ( %) the general dosing recommendation was not respected. the loading dose was inappropriate in cases ( %) and the proper follow up of serum levels of vancomycin has not been carried out in cases ( %). the duration of antibiotic therapy was in compliance with the protocol in cases ( %) and a slight longer duration was observed in cases ( %). finally the overall degree of conformity of the prescription was observed in cases ( %) only. table . in the sfar srlf guideline, the limitation of the echinocandins use to the benefit of ampho deoxycholate explains most of the poor agreement or consensus rate between investigators. the idsa escmid guideline are more helpful to guide indications of empirical treatment which mainly explains their higher rate of both applicability and agreement rate. the rates of agreement do not reflect whether the choice between different class iii antifungal therapies is the best or not. conclusion: the idsa guideline seems to take a broader spectrum of clinical situations into account, particularly in guiding more precisely indications of empirical treatments. escmid or idsa reach more often consensus at the first reading. ( ), and was discovered during a chest x-ray examination for % ( ). diaphragmatic paralysis was confirmed for all cases with chest ultrasound. % of patients ( ) were receiving mechanical ventilation at the moment of the diagnosis. the paralysed hemidiaphragm was left sided in % ( ), and right sided in % ( ). there was no bilateral diaphragmatic paralysis. hemi-diaphragmatic plication was performed in % of the patients ( ), and median time from cardiac surgery to surgical plication was days (range - days). indications for plication were failure to wean from ventilator ( %, ), and respiratory distress ( %, ). plicatured patients were remarkably younger (median age at cardiac surgery- days, range - days) than non-plicatured patients ( . months, range days- years). the median ventilation time after plication was days (range - days). all patients were asymptomatic after diaphragmatic plication. two patients died ( %). cause of death was independant from surgical plication (cardiogenic shock, septic shock). conclusion: diaphragmatic paralysis is a rare but serious complication of cardiac surgery in children. it commonly occurs after open-heart surgery, and specifically after arterial switch operation. plicatured patients were younger than non-plicatured patients and needed more frequently a ventilatory support. a closer monitoring may be required for young patients and mechanically ventilated patients. indeed, both are more likely to be treated by a diaphragmatic plication, reducing mechanical ventilation and intensive care duration. a prospective study. consecutive children aged between days and -year-old admitted to the picu, intubated and mechanically ventilated were eligible and they reached inclusion if they had at least one chest tube. ppl was directly measured by a pressure transducer connected through a needle inserted into the existing chest tube. pes was measured by both a specific probe (gaeltec probe) and by the feeding tube after mobilization (pes-ft). results: patients (median age months (interquartile + - )) were included and exploitable signals were finally available in patients, who were included in the analysis. most of patients (n = ) were admitted after cardiac surgery and had a spontaneous breathing activity. median pes measured by gaeltec probe and by feeding tube was . (interquartile + . - . ) and . ( . - . ) cm h o, respectively. median ppl measured into the chest tube was . ( . - . ) cm h o. bland-altman plots are represented in the figure. conclusion: both ppl measured into the chest tube, pes measured by the gaeltec probe or by the feeding tube are reproducible methods. . respiratory syncytial virus was identified in infants ( %). an initial caffeine citrate loading dose of mg kg was usually administered, followed by a mg kg day maintenance dose, for a median treatment duration of days [ ] [ ] [ ] [ ] [ ] [ ] . therapeutic management (invasive and non-invasive ventilation, nutrition support) and clinical outcomes (death, length of stay) were similar between groups. there was no difference in potential caffeine adverse effects between groups or within the caffeine exposed group pre and post-caffeine administration. conclusion: caffeine treatment of bronchiolitis related apnea seems to be a standard practice in our picu. our study failed to show any influence of caffeine on clinical outcomes in this indication when compared with a small number of patients. further studies are needed to assess the efficacy and safety of caffeine treatment in this indication as well as the appropriate treatment regimen as pharmacokinetic data suggest that higher dose could be of great interest in this non-prematurely born population. introduction: during the last decade, many authors have raised awareness concerning the increasing rate of venous thromboembolism (vte) in critically ill children [ ] . the presence of central venous catheter (cvc) is one of the most important risk factor for venous thrombosis in children [ ] . the purpose of this study was to analyze incidence and risk factors for catheter-related thrombosis in children admitted in our pediatric intensive care unit (picu). patients and methods: all children aged less than years, admitted in the picu from january to june , and receiving at least one tunneled cvc, were included in our retrospective study. those with venous thrombosis unrelated to cvc placement were excluded. catheter-associated venous thrombosis (cavt) was confirmed using doppler ultrasonography. introduction: weaning from the ventilation is a crucial moment in the icu stay. because of the risks of mechanical ventilation (mv), such as ventilator-associated pneumoniae, it is recommended to begin the weaning process as soon as weaning criteria occurs [ ] . however, extubation is also a hazardous period, with to % of subsequent respiratory failure requiring reintubation, harboring a dismal prognosis [ ] . international guidelines display the criteria triggering the extubation. nevertheless, the physician in charge eventually takes the decision to extubate. in this regard, there could be variations from an individual to another. the main goal of our study was to identify the perceived impediments to mv weaning among physicians, from intubation to extubation. patients and methods: prospective single center study in a bed university icu. all patients admitted between february and may and undergoing mv were included. we daily registered the existence of the criteria recommending a spontaneous breathing trial (sbt), the occurrence of a sbt, the items recommending postponing extubation, and the occurrence of an extubation. the estimated reasons for all the aforementioned decisions were asked to the physician in charge. results: patients were included, gathering days of mv and sbt. the average duration of mv was . ± . days. there was one extubation failure requiring reintubation. there were sbt failures. in cases, sbt was a success but did not lead to extubation because of hypotonia, weak cough, subsequent respiratory failure, hemorrhagic bronchial secretions, hemodynamic instability, absence of weaning criteria, drowsiness (all the aforementioned n = ), post sbt hypercapnia (n = ). out of the sbt ( %) were done while one or several weaning criteria were absent. impediments to weaning trials were different according to the time lag since icu admission, with fluid overload, muscular weakness and persistent need for assist control ventilation settings being the most frequent reasons advocated after days (figure). no objective assessment of muscular or cough strength was performed at any time, neither was monitored the rr vt, vital capacity or inspiratory pressure. . % of patients had otolaryngologist follow-up. the overall mortality of the studied population was . % including mortality related to tracheostomy in patients. the tracheostomy for extended mechanical ventilation was significantly associated with an increase of mechanical ventilation duration before tracheostomy (p < . ), duration of mechanical ventilation (p < . ), length of stay in intensive care unit (p < . ) and mortality rate (p = . ). introduction: acute renal failure complicating surgery has a particularly harmful prognosis, with a mortality of % to %. this high mortality rate is attributed to patient-related factors, the severity of the disease and the type of surgery, but not to the acute renal failure itself. the aim of our study is to elucidate the prognostic factors of acute renal failure in the postoperative sepsis in a series of patients. it is a retrospective analytical descriptive study spread over a period of years (from january to december ), observations of postoperative peritonitis were collected in the service of resuscitation of surgical emergencies of chu ibn rochdof casablanca. the statistical analysis was carried out using the spss software. the results are expressed with or and % confidence intervals (ci at %). the results were considered significant when p is < . . the mean age of the patients was ± years with a sex ratio of . ( m ) . renal failure was the most frequent failure after hemodynamic failure, patients were oliguric, anuriques and patients had a preserved diuresis, patients were divided according to the rifle (r %, i %, f %) and akin (i %, ii %, iii %). the predictive factors of acute renal failure ari were studied in univariate and multivariate analysis, factors were retained including catecholamines-or . + ci at % between . and . + p = . + the surgical site-or . + ci at % between . and . + p = . . conclusion: acute renal failure is an independent factor of mortality in the post-operative sepsis, but remains that its presence is a pejorative prognostic factor. this was a retrospective study performed in a large university hospital. all patients receiving the molecule were included in the analysis. indication for sodium lactate, dose, and modality of administration were collected. we also collected clinical and biological variables before sodium lactate infusion, after h (h ), and after h (h ). an analysis of the evolution of these variables at h and h was performed. results: between january and may , patients, aged years, % males, sofa score [ - ], received an infusion of molar sodium lactate ( ml ). main indications for sodium lactate were hyperchloremic metabolic acidosis ( %), vascular filling ( %), mixed acidosis ( %), and intracranial hypertension ( %). % of the patients presented with a chloride sodium ratio > = . at basal time. sodium lactate was associated with a significant increase of mean arterial pressure at h (p = . ) and h (p = . ), a decrease of catecholamine dose (p = . ) and heart rate (p = . ) at h , and an increase of diuresis in the h period following initiation of the treatment (p = . ). we observed an increase of ph, bicarbonate, base excess, and sodium, at h and h (all p < . ). plasma lactate concentration was increased at h (p < . ), but was not different from basal value at h (p = . ). there were no significant variation of plasma chloride. chloride sodium ratio was significantly reduced. plasma sodium > = mmol l and ph > = . at h were observed in % of the patients. this retrospective study reports the largest number of critically ill patients having received sodium lactate. hemodynamic effects observed in this study are concordant with the data of the literature. the metabolic effects observed in this study, with rapid increase of ph, bicarbonate, and base excess, strongly suggest the potential interest of sodium lactate among critically ill patients presenting with acidosis and increased chloride sodium ratio. introduction: acute kidney injury (aki) is a frequent and severe condition in intensive care unit patients that may require renal replacement therapy, most frequently continuous renal replacement therapy (crrt). although hypoglycemia is a well-known complication of crrt using glucose free solutions, euglycemic ketoacidosis (eka) has never been described in this setting. patients and methods: all anuric patients with glucose free crrt solution induced eka (february -may ) were prospectively included and evaluated. ketoacidosis was deemed possible when nonlactic metabolic acidosis did not improve in patients on crrt. because all patients were anuric, we measured ketonemia and used urinary test strip in the effluent fluid. eka diagnosis was retained when arterial serum bicarbonate was < meg/l despite crrt, in the absence of lactic acidosis and in the presence of ketones in the serum or crrt effluent fluid. results: eighteen patients ( % of our patients under crrt in this period) developed eka during crrt using glucose free solution (phoxilium ® ). time between cvvhdf initiation and ketonemia detection was ( - ) days. patient characteristics are presented in the table . half of them had for a medical history of diabetes ( insulindependent). only patients were receiving insulin and most of them had low glucose or food intake. increasing glucose intake and insulin infusion resolved ketonemia in all cases. discussion: we describe for the first time the occurrence of euglycemic ketoacidosis in critically ill patients under crrt using glucose-free replacement solution. common features of the patients were multiple organ failure with anuria, normal glycemia without insulin infusion and low glucose infusion or food intake. critical illness-induced insulin resistance and starvation could altogether contribute to ketoacidosis even if acidosis is unusual in starvation ketosis. by removing substantial amounts of glucose from the blood, crrt with glucose free solution could worsen this condition, mask hyperglycemia and induce euglycemic ketoacidosis. in critically ill patients on crrt using glucose free solution, euglycemic ketoacidosis is common and should be detected, especially in patients with low glucose intake, no insulin infusion and unexplained metabolic acidosis. importantly, the diagnosis can be missed in anuric patients with normal blood glucose and in the absence of known diabetes. since, cvvhdf-induced ketoacidosis may contribute to persistent acidemia and its adverse effects, serum or crrt effluent fluid ketone level should be measured in this setting. . - ] years. main reasons for admission were hypercalcemia (n = ( . %)), followed by acute encephalopathy (n = ( . %)). median saps ii and sofa scores were [ . - . ] and [ ] [ ] [ ] [ ] [ ] respectively. main causes of hcm were hematological malignancies (n = ( %)), solid tumors (n = ( %)), iatrogenic events (n = ( %)) and endocrinopathies (n = ( %)). median calcium levels at admission, at day and at icu discharge were . [ . - . ], . [ . - . ] and . [ . - . ] mmol l respectively. more than half of the patients (n = ( %)) recovered from hcm days after icu admission. acute kidney injury occurred in ( %) patients and ( . %) patients required dialysis. neurological complications concerned ( . %) patients, mainly delirium (n = , . %). digestive events occurred in ( . %) patients. cardiovascular events concerned ( %) patients and consisted in de novo hypertension in ( %) patients, and ekg disturbances in ( %) patients. during icu stay, ( . %) patients required mechanical ventilation and ( . %) patients required vasopressors. volume resuscitation with crystalloids was the first treatment in ( . %) patients, ( . %) received bisphosphonates and ( . %) received corticosteroids. respective icu and hospital mortality were . and . %. there was no correlation between the degree of hcm and icu mortality (p = . ). icu and hospital mortality were associated with the underlying disease (hematological malignancies (p = . )). conclusion: hcm is associated with high mortality rates. the increased mortality is a consequence of the main mechanism, mainly underlying malignancy rather than hcm per se. the course of hcm may be complicated by organ failures that are most of the time reversible with early icu management. introduction: sepsis is one of the leading cause of death among patients with chronic kidney disease (ckd). the mechanisms of this higher mortality remain poorly understood. sepsis and chronic kidney disease are both conditions associated with a higher plasmatic concentration of bile acids. the farnesoid x receptor (fxr) is a key regulator of the bile acid metabolism and has recently been involved in the regulation of the inflammasome during sepsis. we explored the role of fxr in the prognostic of sepsis in an animal model of ckd. patients and methods: sepsis was provoked by the injection of . mg kg of lps weeks after the creation of ckd. the ckd was created by unilateral nephrectomy associated with contralateral thermocauterisation. the mice (c bl j) were randomly assigned to one of the following groups-sham placebo, ckd placebo, sham lps or ckd lps. a fifth group of ckd lps mice received a treatment with sevelamer (a bile acid sequestrant) during weeks. survival of the animals, serum biochemistry and molecular biology in the kidney were performed after sacrifice. results: whereas the sham lps animals survived, all ckd lps animals died during the h following the injection of lps. the plasmatic urea, il beta and tnfa concentrations increased with the creation of ckd (ckd placebo versus sham placebo animals) and with the creation of sepsis (ckd lps versus sham lps groups). whereas the expression of fxr rna did not changed with the injection of lps in the sham animals (sham lps versus sham placebo), the fxr rna decreased with the creation of sepsis in the ckd animals (ckd lps versus ckd placebo groups). the ckd animals treated with sevelamer weeks before the administration of lps (ckd sev lps group) had a lower plasmatic concentration of il b, tnfa and increased the rna expression of fxr in the kidney compared to the ckd lps group. also, the treatment with sevelamer improved the survival of the ckd lps animals. conclusion: our study demonstrates a relation between fxr and the prognostic of sepsis in ckd animals. the exact link and the potential therapeutic interest of targeting fxr and bile acids metabolism in ckd patients remain to be studied. introduction: dysnatraemia, dyskalaemia and hypomagnesemia are frequent metabolic disorders in intensive care, and their causes represent a major concern for the intensivist, especially in urgent conditions. in the diagnostic approach, we often use the urine analysis. although measurement of -hour urine electrolyte excretion ( -hu) is considered the most reliable method, the great burden and difficulty in collecting complete -hour urine has prompted the search for more practical methods, such as spot urine analysis. the aim of the present study was to compare electrolyte excretion in urine samples collected over different time periods, in comparison with a -hour urine sample collection considered as the gold standard method. patients and methods: this prospective and descriptive study included patients admitted in a tunisian medical icu, between september and december . baseline characteristics, medications and laboratory data including electrolytes and renal function parameters were obtained from all patients. multiple urine specimens for analyzing na + k + mg + urea + ca + phosphate + creatinine + proteins and uric acid were obtained from -hour, -hour and -hour urine samples during day and night time, and results were compared with those obtained from the gold standard method ( -hour urine collection). correlation analysis was performed using the spearman test. results: significant correlation was found for all biochemistry parameters between -hour urine results and those obtained from -hour and -hour samples regardless of day or night sampling. a comparative analysis for sodium and potassium is shown in fig. . conclusion: determination of electrolyte excretion from urine samples taken over different time periods, and h, provides a reliable estimation of -hour urine electrolyte excretion. it appears practical for early understanding of the mechanism of electrolyte imbalance. however, further studies are warranted to confirm the usefulness of this approach. use of the procalcitonin assay in an adult emergencies department: retrospective experience of a general hospital of the suburb of paris ( . - . ). other markers of infectious were poorly recorded (fibrinemia in ( . % + . g l [ . - . ] + immature forms on blood count- . %). only ( . %) had blood cultures in the ed ( patient [ ] [ ] ) and ( . %) other(s) microbiological sample(s), mainly urinary ( patients [ . % + among them % considered as positive]). % of blood cultures were positives, mainly for gram negatives ( %). final diagnosis in the ed was considered as infectious disease (id) in only patients ( . %, including sepsis and septic shocks). ( . %) was considered as non-infected (nid) and final diagnosis remains unprecise in ( . %). pct values was of . ( - . ) in the id vs. ( - . ) in the nid (p < . ), wbc was of . in the id vs. . in the nid (p < . ) and crp was of ( . - . ) in the id vs. ( - ) in the nid (p < . ). no correlation was observed between the pct value and admission to dechocage room admission. . identification of the involved drug was obtained in % of the cases, based on qualitative screening. management was mainly supportive and included sedation ( %), naloxone ( %) and flumazenil ( %). tracheal intubation was required in patients ( . %). one cardiac arrest but no death occurred in the ed. forty-three patients ( %) were transferred to the intensive care unit. conclusion: our dataset provides an interesting insight into the drugs involved in and clinical pattern of toxicity outcome of acute recreational drug toxicity presentations at the ed, despite possible under-declaration and coding. classical recreational drugs were more common ( %) followed by prescription drugs ( %) and nps ( %). and drug ( %) consumers + hiv-infected ( %) and depressive ( %) patients) were admitted to the icu. the main declared compounds were methylenedioxypyrovalerone (mdpv + n = ), -methylethcathinone ( -mec + n = ), -methyl methcathinone ( -mmc + n = ) and -methyl methcathinone ( -mmc + n = ), more frequently used in drug mixtures sold as bath salts or in poly-intoxication with conventional illegal drugs (mainly cocaine and gamma-hydroxybutyrate). nps was used in a recreational ( %), chemsex ( %) or solitary practice ( %). binge ( %) and intravenous ( %) self-administration was remarkable. patients presented acute encephalopathy with psychomotor agitation ( %), confusion ( % + glasgow coma score- [ ]), hallucinations ( %), anxiety ( %), seizures ( %), myoclonus ( %) and stereotypes ( %). ecg typically showed sinus tachycardia ( %), qrs qt abnormalities ( %) and atrio-ventricular block ( %). acute cardiac ischemia ( %) and dysfunction ( %), disseminated intravascular coagulation ( %) and multiorgan failure ( results: during the first and the second study periods and patients were respectively admitted in the icu. total micro-organisms density was and . for patients for the first and the second period, respectively (p < . ). acinetobacter spp and pseudomonas aeroginosa were the predominant isolated microorganisms with a respective density of . and . isolates for patients. figure summarizes the patterns of bacterial ecology and resistance in our icu before and after transfer to new buildings, showing a significant decrease in pseudomonas aeroginosa resistance for ticarcillin and ceftazidim, whereas acinetobacter resistant to carbapenems and enterobacteriacae esbl significantly increased. our study suggests that transfer of icu to the new buildings was associated with a decrease of pseudomonas aeroginosa resistance, whereas acinetobacter spp resistance and esbl enterobacteriacae incidence increased. introduction: infections caused by antimicrobial-resistant bacteria (amrb) are one of the main issues in the spectrum of critically ill patients as they are associated with higher mortality, morbidity, and length of stay. thus, an appropriate initial antimicrobial therapy is decisive for better patient outcomes. the aim of the study is to determine the adequacy of first-line antibiotic therapy guided by weekly amrb screenings. patients and methods: a months prospective study was conducted in -bed micu. were included all patients with more than h of icu stay. an amrb screening was conducted upon admission and on weekly basis for all the patients. the choice of antibiotherapy if indicated, was guided by the most recent colonization results. if the patient has received at least one active in vitro antibiotic against the isolated bacteria, the empiric antibiotherapy was considered appropriate. results: patients were included in the study. mean age and saps ii were respectively ± years and ± . the median length of stay was days. ( %) patients were colonized by amrb upon admission. the most frequent isolated microorganisms were-escherichia coli ( %) and klebsiella pneumonia ( %). were assessed hospital-acquired infections (hai)- ( %) in amrb colonized patients and ( %) in uncolonized ones. the antibiotherapy was considered appropriate in infections ( %). out of the colonized patients, ( %) developed hai. ( %) patients had a concordant colonization body site to the infection. of the nosocomial infections, ventilator-associated pneumonias and central venous catheter infections were the most frequent, both at % (n = and n = ) + followed by urinary tract infections % (n = ) and infective endocarditis % (n = ). ( ). overall, the isolates were-extended spectrum betalactamase productrice-enterobacteria ( %), imipenem resistant-acinetobacter baumanii ( %), and multi resistant-pseudomonas aeroguinosa ( %). ni were documented including caused by mdr bacteria and distributed as follows-ventilator acquired pneumonia-vap (n = ), bacteraemia (n = ), vap with bacteraemia (n = ), catheter related infection-cri (n = ), cri with vap (n = ) and catheter-related bacteraemia-crb (n = ). the performance of mdr bacteria-screening in predicting ni was poor with % of sensitivity, % of specificity, . % of negative predictive value (npv), and % of positive predictive value (ppv). nevertheless, the performance of the nasal swab in the prediction of vap was better with % of sensitivity and . % of npv. conclusion: mdr bacteria-screening is useful as it allows to identifying the mdr bacteria-carriers and helps for a rational use of antibiotics in severe ni. however, its diagnostic contribution in the occurrence of ni is poor except the interest of the nasal swab in the prediction of vap owing to its good npv. we aimed at determining the respective weight of these phenomenon and the physiological determinants of the respiratory variations of the ivc diameter. patients and methods: in mechanically ventilated patients (tidal volume- . ± . ml kg of predicted body weight) haemodynamic, respiratory and the intra-abdominal pressure (iap) signals were continuously computerised. cvp, iap and the ivc diameter (transthoracic echocardiography) were recorded during -second end-inspiratory and end-expiratory occlusions separated by s, before and after the infusion of -ml of saline. patients in whom fluid administration induced an increase in cardiac index (picco- ) > % were defined as "responders". the respiratory variations of the ivc diameter, cvp and iap were calculated as the (end-inspiratory-end-expiratory values) mean value. the compliance of the ivc was estimated by the ratio (end-expiratory-end-inspiratory ivc diameter) (end-expiratoryend-inspiratory cvp). results: fluid administration increased cardiac index by more than % ( . ± . to . ± . l min m , p = . ) in patients. the respiratory variations of the ivc diameter predicted fluid responsiveness (area under the roc curve- . ( % ci . - . ), p < . ). before fluid administration, the ratio of changes in ivc diameter over changes in cvp was not different between responders and non-responders ( . ± . vs. . ± . mm mmhg, p = . ). before fluid administration, the respiratory variations of the cvp tended to be higher in responders than in non-responders ( ± vs. ± %, p = . ). the respiratory variations of the ivc diameter were associated with the respiratory variations of cvp (r = . , p = . ) but not with the respiratory variations of iap (r = - . , p = . ). the respiratory variations of the ivc diameter were not explained by a higher ivc compliance but rather by higher respiratory variations of the cvp in responders than in non-responders. interestingly, it seems that iap, the ivc extramural pressure, was not involved in the respiratory variations of the ivc diameter. inclusions are ongoing. during the hospitalization in icu, there was no significant difference between the two groups regarding the proportion of patients with aki through icu discharge. in the intervention group, % of the patients had a glomerular filtration rate lower than ml min . m compared to . % in the control group (p = . ) at day- . we found no significant difference between the two groups neither on hematopoietic effects of epo or serious adverse events. in patients resuscitated from an ohca of presumed cardiac cause, early administration of erythropoietin compared to standard therapy did not confer any renal protective effect. salvetti marie , and the ratio of end-diastolic areas of both the right and left ventricle in the long axis view of the heart (rveda lveda) were measured. a lvef < % defined lv systolic dysfunction, a ci < l min m defined low cardiac output, and a rveda lveda ratio > . (± associated with a paradoxical septal motion in the short axis of the heart) defined rv dysfunction (± acute cor pulmonale). the preload-dependence was evaluated using deltasvc or deltavmaxao. front-line hemodynamic and metabolic parameters were recorded at the time of tee assessment. results: lvef and ci could be simultaneously measured in of patients ( %). patients ( %) had a low ci related to lv systolic dysfunction (lactate- . ± . mmol l), patients ( %) had a low ci and a preserved lvef related to a rv dysfunction or to a sustained preload-dependence (lactate- . ± . mmol l), patients ( %) had preserved ci and lvef (lactate- . ± . mmol l) including only patients ( %) with a hyperkinetic profile (high ci and lvef > %), and patients ( %) had preserved ci but altered lvef (lactate- . ± . mmol l) due to a marked tachycardia. none of the front-line hemodynamic parameters was discriminatory to identify the circulatory profile identified by tee assessment (table) . introduction: aortic end-systolic pressure (esp) is considered as a reliable index of left ventricular afterload. recently, the effective arterial elastance (ea), i.e., the ratio of esp over stroke volume (sv), has also been proposed as a reliable afterload index. our aim was to document peripheral estimates of ea (eapsap) at the bedside in critically ill patients, and to investigate the haemodynamic mechanisms responsible for ea changes after fluid administration (fa). in the validation study, carotid tonometry (complior) was prospectively performed on haemodynamically stable spontaneously breathing patients equipped with an arterial femoral (n = ) or radial (n = ) catheter. ea was defined as the ( . × csap) sv ratio, where csap was the central systolic arterial pressure directly measured from the calibrated carotid waveform. eapsap was calculated as the ( . x peripheral systolic arterial pressure) sv ratio. sv was obtained by transpulmonary thermodilution or transthoracic echocardiography. in the clinical study, we included patients with invasive haemodynamic monitoring (picco- ), in whom fa was planned. results: in the validation study, the complior allowed estimating ea in all patients (ea = . ± . mmhg ml). the (eapsap-ea) bias was smaller at the femoral than radial artery level ( . ± . vs. . ± . mmhg ml, p < . ) and was strongly related to the systolic pressure amplification between the carotid and peripheral artery (r = . , p < . ). ea was more strongly related to sv (r = − . ) than to esp (r = . ) (each p < . ). the four-quadrant plot analysis indicated that patients ( %) exhibited a concordant low ea high sv pattern or high ea low sv pattern, while only patients ( %) exhibited concordant high ea high esp pattern or low ea low esp pattern (p < . ). there was a negative relationship between changes in eapsap and changes in sv in the whole population, in fluid responders (cardiac index increases > % after fa), in pressure responders (mean arterial pressure increases > % after fa) and in non-responders, while no consistent relationship between eapsap and esp changes was documented. conclusion: ea may be reliably estimated at bedside by using the ( . x femoralsap) sv ratio. ea value and ea changes induced by fa were related to sv rather than to esp. thus, ea should be considered as an index reflecting sv rather than left ventricular afterload in critically ill patients. this study included a sham group (n = ), a cpb group (n = ), an ir group (n = ) and a cpb-ir group (n = ). rats were exposed to min of cec, min of left pulmonary ischemia and min of reperfusion. fonctional endothelial dysfunction was evaluated by measurement of the pulmonary artery reactivity. systemic inflammation was evaluated by the plasma assay of il- beta, il- and tnf-alpha. the endothelial glycocalyx was evaluated by plasma assay syndecan- and electron microscopy. the statistics were performed using an anova test, p < . . we showed that cpb associated with ir induce an endothelial vasorelaxation dysfunction mainly mediated by nitric oxyde (no introduction: during circulatory shock, the goal of increasing cardiac output is to correct tissue hypoxia, which can be manifested by an increase in oxygen consumption (vo ) associated with an increase in oxygen delivery. we hypothesized that, in patients in circulatory shock, veno-arterial co gradients (pv-aco ) could be a good predictor of an increase in vo in fluid responders. patients and methods: we included patients with circulatory shock who received a fluid challenge. circulatory shock was defined by the association of vasopressor requirements to maintain mean arterial pressure (map) and a blood lactate concentration ≥ mmol l. we measured cardiac index (ci) and arterial and central venous blood gases and arterial lactate before and after a volume expansion ( ml of plasmalyte ® ). cardiac index (ci) was measured using a pulse contour analysis method (picco + pulsion, munich, germany). ci responders were the patients in whom ci increased (Δci) by > %. in those patients, vo responders were those in whom vo increased (Δvo ) by > %. receiver operating characteristic (roc) curves were performed. the data was presented as median ( th percentile- th percentile). a p < . was considered as statistically significant. introduction: the autonomic nervous system (ans) is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of ans activity and a relation between hrv and outcome has been proposed in various types of patients. while electrocardiographic hrv assessment seems to be the gold standard, we evaluated the feasibility of an automated hrv monitoring based on standard photoplethysmographic monitoring. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct ) that aims to record more than icu patients over a -years period. introduction: diabetic ketoacidosis is an acute complication of diabetes, defined as metabolic acidosis with a high anionic gap, associating hyperglycemia > mmol l ( g l), positive ketonuria, or superior or equal ketonuria to ++, it is a medical emergency which can occur in a known diabetic patient, or not. objective-to describe the clinical therapeutic and prognostic aspects of diabetic ketoacidosis in the intensive pediatric care unit at the ehs canastel oran, algeria. patients and methods: retrospective study carried out over a period of years. from january , to january , , in the intensive pediatric care service. the data was entered and analyzed using excel . results: cases were retained on hospitalizations per year, % of cases had no history with diabetes, % occurred in known diabetics with insulin, but are not followed medically. our patients were aged from months to years, but the average age of these patients was years and months, with a slight female predominance, coma was preceeded by % of cases polydipsy polyuria syndrome and % weight loss, triggered by an infectious syndrome including % of ent cases, % of respiratory infections and % of cases with digestive infections characterized by fever, abdominal pain, vomiting. the delay between diagnosis and admission to ice was - days. at admission % of patients were scored at on the glasgow scale, with presence of the cough reflex, and % were scored at < requiring tracheal intubation and mechanical ventilation of h with signs of dehydration and ionic disorders, namely hypokalemia and hypernatremia, blood glucose at admission varies between . and g l with glycosuria at +++ and ketonesuria between ++ and ++++ in only % of the patients had metabolic acidosis, a cerebral computed tomography (ct) performed in % of cases found a slight cerebral edema. therapeutic management was the rehydration, correction of metabolic disorders and introduction of insulin into sap, with monitoring and subcutaneous relaying due to ketonuria negativity. the outcome was favorable for all patients. conclusion: diabetic ketoacidosis is a major complication of diabetes which can be avoided by a good prevention campaign and systematic screening of any child suspected of diabetes, recognition of risk situations such as infections and clinical manifestations in order not to delay the management. introduction: scorpion sting is a public health problem world wide with a global distribution of species. in algeria, scorpionic envenomation occupies a prominent place in declarations. in , cases were reported. the objective of our study is to describe the epidemiological, diagnostic, therapeutic and evolutionary characteristics of the scorpion sting in children. retrospective study of cases of scorpionic envenomation hospitalized in the pediatric resuscitation department of the ehs canastel oran conducted during the year the inclusion criteria were the presence of traces with at least one locoregional or general clinical signs. the parameters studied-age, sex, city of origin, time of bite, time of management, initial first aid, time limit for admission to pediatric intensive care, and severity criteria. results: % of these cases were boys and % girls. the mediane age . % of the punctures occurred during the day, the site of the injection was the lower limb in % of the cases and there were bites scorpion cases in the west of algeria and exactly in oran and tiaret. of the cases was the upper limb. the delay of the management was from to h for of the cases who were classified in the third classed according to the clinical signs of gravity. the type of the scorpion was not identified. we can classify all the patients that we received in our service into three classes − % in class i, with local signs such as pruritus, redness, abnormalities and local pain. eva - , calmed by the infusion of mg kg iv of paracetamol and application of xylocaine cream at the site of the sting. introduction: the residence of children in intensive care is most often due to the existence of one or more organ dysfunction which requires heavy treatment (intubation, ventilation, drainage, venous tract) and this in a hostile environment which amplifies the aggression organic. the main objective of our work is to study the consequences of hospitalization of children in pediatric resuscitation. patients and methods: this is a descriptive prospective study on the outpatient consultation file of canastel's ehs multipurpose resuscitation. we studied files and assessed memory, perception of contact and nuisance factors felt by sick children. results: out of children seen in post resuscitation. the sex ratio is . . the average age of children is years ( months- years). the average hospital stay is days. the average gos (glasgow out scale) is . ( ) ( ) ( ) ( ) . the average duration of ventilation is days. % of children had central vascular access. three children describe a total memory of the stay, some memory and none. three children have a good perception about the staff, one child dissatisfied and three others indifferent. the nuisance factors described by the children are pain ( ), cold ( ), noise ( ), hunger ( ) and light ( ) . conclusion: consequences of psychological trauma, insufficiently evaluated especially by the staff, which result in the appearance of psychological disorders (nightmares and anxiety) with sometimes even severe post-traumatic neurosis. hence the need to adapt the environment and mainly noise and respect for sleep. [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the median treatment duration time was at ( - ) minutes. femoral vein was used as vascular access ( %) and most of pe procedures ( %) were performed with citrate anticoagulation. median exchange volume was at [ - ] ml and renal replacement fluid was fresh frozen plasma (ffp) in %, % ffp and % human albumin % in % and human albumin only in % of procedures. adverse effects were observed in less than % of procedures and % were lifethreathening including cardiac arrest, heart rhythm disorders, cerebral oedema and hemolysis. other remaining complications were secondary infections %, hemorrhage %, and pulmonary oedema % in all patients. twenty patients deceaded (icu mortality %). icu and hospital lenght of stay was at ± and ± days respectively. of survived patients still underwent pe after their icu discharge + totally recovered whereas ( %) were on partial remission. conclusion: pe is a routine and feasible technique in icu. this study showed that tpp was the most commonly indication of its use and that outcome was fair. adverse effects frequently occured but most of them were not severe. further studies would benefit form larger cohort to improve indications, delay of initiation and practice of this treatment. renal replacement therapy was required in % of elderly versus % (p = . ). frequency of ttp, hus and ahus was similar beetween groups. tma was more frequently associated with ongoing cancer and drug use in elderly ( vs. %, p < . and vs. %, p < . , respectively). gastro-intestinal bleeding during icu occurred more often among elderly ( vs. % (p = . )). icu mortality rate was higher ( vs. %, p = . ). no difference was found concerning plasma-exchange therapy, steroids use, and rescue treatments for refractory-ttp. discussion: increased complication and mortality rates in the elderly group might be ascribed to more cardiovascular morbidity in this population. the association between tma and ongoing cancer suggests a routine oncological workup among elderly. introduction: neutropenia, defined by an absolute count of polymorphonuclear neutrophils less than < mm , exposes patients to infectious complications that can lead to sepsis or septic shock. the mortality risk is higher. the french guidelines published in were formulated to homogenize the clinical practices and improve survival. we performed a monocentric retrospective study including all consecutive patients admitted to the medical icu of a tertiary hospital to a neutropenia with sepsis or septic shock, between the th of december and the th of december . the study protocol was approved by the local ethics committee ( . ce ) and published on clinical trial (nct ). results: patients were admitted in icu during this period. patients ( %) presented a neutropenia with sepsis or septic shock. among these patients, % had hematologic malignancies and % had solid tumour. patients ( %) was treated empirically with antipseudomonal beta-lactam or carbapenem and aminoglycoside. ( %) skin or suspected catheter-related infections were treated with anti-mrsa (methicillin-resistant staphylococcus aureus), vancomycin or linezolid. adequate antibiotics as described in guidelines was performed to patients ( %). patients ( %) received aminoglycoside ( patients received initial dose in icu, patients complement dose) and ( %) received anti-mrsa with antipseudomonal betalactam or cabapenem. patients ( %) had microbiologically documented infections with, % of bacteria ( % of gram-posit cocci, % of gram-negative cocci, % of gram-negative bacillus), % of fungi and % of viral infection ( table ) . among of them, % ( ) of esbl, % ( ) of mrsa and % ( ) of emerging highly resistant bacteria (bhre). the icu-mortality rate was % ( ) with % of -day mortality ( ). the curves of the cumulative incidence of death risk between d and d were no different according to adequate empirical antibiotic treatment as like french guidelines (fig ) . by multivariate analysis, independent factors of adequate antibiotic treatment were septic shock (or, . + % ci . - . ) and febrile neutropenia > days (or, . + % ci . - . ) at icu admission. conclusion: according to the usual clinical practice, septic neutropenic patients was already treated empirically by bitherapy including antipseudomonal or anti-mrsa if there is a skin or suspected catheter-related infection. adjunction of aminoglycoside in of the symptomatology in case of overdose, make the diagnosis difficult, especially since the drug in question is often unspecified and the toxicological analysis is not exhaustive. introduction: carbon monoxide intoxication is a public health problem in tunisia and around the world. currently, it is unclear the impact of this type of poisoning in our country for lack of declarations. we propose in our work to study the epidemiological characteristics of fatal carbon monoxide intoxications collected in the forensic pathology department of the university hospital in sfax, tunisia, to describe the different steps used in forensic diagnosis of fatal carbon monoxide intoxication and to propose preventive measures to reduce the rate of these intoxications. patients and methods: it is a retrospective study of cases of fatal carbon monoxide intoxications collected in the forensic pathology department of the university hospital in sfax, tunisia during years ( january to december ). commemoratives were collected from medical and police records. a forensic autopsy and a toxicological analysis were carried out in all cases. results: fatal carbon monoxide intoxication is the leading cause of toxic death in sfax during the period of our study. we notice a decrease in the incidence of this type of intoxication. the average age of deaths was years and months with male predominance. the peak frequency of intoxication was in cold season. the most frequent form of intoxication was accidental. the source of carbon monoxide was mainly the defective water heater often placed in poorly ventilated areas. the classic carmine red-color of lividity was found in the majority of cases. myocardial distress, favored by hypoxia, has been reported in two subjects with a pathological coronary artery. the mean hbco level was . %. however, account must be taken of the survival time and the time elapsed between death and dosing of hbco. the incidence of fatal carbon monoxide intoxication has decreased since and the victim profile has not changed too much. the fatal carbon monoxide intoxication is still persists as a public health problem in tunisia. the reduction of its frequency requires the implementation of a well-structured prevention plan based on epidemiological data from a national registry. the identification of these data requires mandatory reporting of this type of intoxication in tunisia. introduction: olanzapine is an atypical antipsychotic drug frequently prescribed in the treatement of bipolar disorder and schizophrenia. acute poisoning with this molecule is rarely reported. through this study we aimed to evaluate the incidence and describe the different clinical features of acute olanzapine poisoning. patients and methods: retrospective analysis of all cases of olanzapine intoxication admitted in -bed teaching icu between january and decembre . inclusion criteria were patient age ≥ year, acute olanzapine intoxication, the intoxication severity was assessed by the poisoning severity score (pss) of the european association of poison centres and clinical toxicologists. the evaluation of electrocardiograms was performed in the first day of hospitalization. the durations of qrs and qtc was measured and arrhythmias and conduction disorders was identified. results: patients were included, the mean age was ± years. they were males and females. long term treatment with olanzapine was noted in patients ( %) who suffered from psychiatic desease. the supposed ingestion dose ranged from to mg. the mean consulting time was ± h after the ingestion. olanzapine was co-ingested with others drugs in patients ( %). co-ingested drugs were-benzodiazepine (n = ), levomepromazine (n = ), serotonin recapture inhibitor (n = ), amitriptilyne (n = ) and biperiden (n = ). the pss was moderate in cases ( . %), severe in cases ( %) and fatal in case. the main clinical signs were tachycardia and miosis in % of cases each of them (n = ), agitation in % of cases (n = ). ecg abnormalities has been detected such as prolonged qtc in cases with a mean duration of ± ms. in the group of monointoxication ( patients) the pss was moderate in cases ( . %), severe in cases ( %) and fatal in one case. the coma glosgow scale was < fig. kaplan-meier survival between admission and -day according to adequate empirical antibiotic therapy guidelines (log rank, p = . ) in cases. mechanical ventilation was required in % of cases (n = %) with a mean duration of ± heures. the mean duration of icu stay was of ± h. twenty three patients recovered during the hospitalisation, one patient died with severe poisoning. conclusion: as showed in this study, acute olazapine poisoning could be severe, and lead to death sometimes. introduction: voluntary drug intoxication (vdi) continues to be a major health problem in many developed and developing countries. in algeria, this has become a worrying concern. awareness-raising is launched to prevent the public from these dangers. vdi are intentional or rarely accidental and can be individual or collective and affect all age groups. the vdi represents the first reason for hospitalization in the emergency department university hospital of oran. in algeria there is no national or regional register of voluntary intoxication. knowledge of the causes of drug poisoning should therefore be extrapolated from foreign studies. to draw up an assessment of the imvs, a retrospective study was carried out over the years ( - ) . this survey consisted of collecting data on the nature of the drug, age, sex, major toxidromes, severe imvs requiring hospitalization in icu, mortality, e.t.c scores and glasgo scores. results: cases of acute poisoning were collected, with a predominance in patients aged between and , a percentage of . %. in addition, most patients were female with . %, a sex ratio of . with p < . . the main toxidromes were-opioid syndrome in % of cases and anticholinergic syndrome in % of cases. etc with a score of > % accounted for % of patients. severe vdi requiring resuscitation hospitalization were %. conclusion: acute poisoning remains high and steady in the oran region and the under- age group represents the most affected category. awareness campaigns must be launched throughout the year to better conserve and store medicines, phytosanitary products and other chemicals. improved socio-economic conditions would help to reduce voluntary intoxication. introduction: scorpionic envenomation is unevenly distributed throughout the world and is particularly frequent in some regions of the world, notably north africa. the purpose of this work is to describe the epidemiological profile of the scorpionic envenomations admitted to the resuscitation department of mahres. patients and methods: a prospective study conducted at the mahres intensive care unit over a period of months ( until ), including all patients admitted for scorpion envenomation. results: we collected cases of patients admitted to the resuscitation department of mahres from to , including cases of scorpionic envenomations, i.e. . %. the median age was years with extremes ranging from to years. the sex ratio was . scorpion stings occurred at night in % of patients, % in the first half of the night (between pm and - pm) and % in the second half of the night ( to h). venom inoculation points were in the lower limbs in % of cases, followed by upper limbs ( %). the color of the incriminated scorpion was yellow in %, black in % and unspecified in % of the cases. for admission classes, there were % class i, % class ii and % class iii. the traditional therapeutic gestures practiced by the patients or their entourage were the laying scarification ( %) and the suction ( %). all patients received anti-scorpion serum, an analgesic, serum and tetanus vaccine. the progression was favorable in all cases after an average hospital stay of ± days. conclusion: scorpionic envenomations are indeed a reality in mahres with a non-negligible frequency despite under-reporting of cases treated by traditional medicine or in other hospitals. they mostly affect young people and the associated clinical manifestations often remain benign. introduction: severe pediatric poisoning is defined by the need for intensive care monitoring due to the nature, quantity of the substance and or clinical manifestations. it is one of the frequent reasons for admission to emergency and resuscitation. the purpose of this work is to identify poisoning in children admitted to pediatric intensive care units in order to assess the frequency, identify the products involved, and the clinical and evolutionary aspects. patients and methods: this is a descriptive study over a -month period in the canastel oran multi-purpose pediatric intensive care unit from july to july . we included all children aged - years admitted for ingestion and inhalation of products toxic. results: children admitted to pediatric intensive care, mean age was years, % under years with extremes of months and years, a female predominance of % was observed with a slight predominance of accidental poisoning ( %) compared to voluntary poisoning ( %). in % the toxic is ingested orally. the most frequent toxicants were drugs with cases ( %), mostly antidepressants and antiepileptics, followed by organophosphates with cases ( %), co cases ( %), petroleum products and plants with cases ( %). the main clinical signs were neurological signs ( %) with predominance of coma and convulsions in cases ( %), respiratory distress was present in cases ( %) and digestive signs cases ( %). for therapeutic management gastric lavage, charcoal and antidotes were the most frequent treatments. the evolution was marked by a mortality of % or a death secondary to a poly-medicinal intoxication voluntary in a girl of years. mechanical ventilation in cases ( %) and an average hospital stay of days. conclusion: acute poisoning is a medical emergency that may require resuscitation. young children are most exposed with drugs are the most frequently incriminated. we propose, as a preventive measure, companions of information on the dangers of toxic products and especially of medicines by the surveillance of the child and the regulation of certain products. introduction: the place of neuron specific enolase (nse) dosing remains uncertain as an indicator of neurological prognosis after a cardiac arrest, the threshold value for predicting an unfavorable evolution being variable from one study to another. our objective was to determine a nse cut-off value predictive of poor neurological outcome after a cardiac arrest. patients and methods: we realized a monocentric prospective trial in a medical icu of a french university hospital from january st to december th . all patients over years old hospitalized for a cardiac arrest in medical icu were included. patients who died during the first h or admitted for cardiac arrest with a neurological cause were excluded. serum nse values (elecsys nse test, cobas ® analyzer) were assessed at h and h after cardiac arrest. somatosensory evoked potentials were recorded between h and h . the primary endpoint was neurological outcome at month using the cerebral performance category scale (cpcs). cpcs or was considered as favorable outcome and cpcs higher than as poor outcome. data were collected using cardiologic or neurologic consultations report, or by phone call to the patient. using a roc curve we determined the nse value at h with higher specificity and acceptable sensitivity. results: we included patients. average age was years old. noflow time and low-flow time were respectively . and min. hypothermia was performed in ( %) patients. patients ( %) died in the icu. the -day and -months survival rates were respectively and % with a favorable outcome of % at months. on the roc curve we found a cut-off value of ng ml with specificity of . ci % ( . - . ) and a sensibility of . ci %( . - . ). area under curve was . ci % ( . - . ). out of the patients with a rising nse between h and h had an unfavorable outcome. among patients with nse > ng ml, the cortical n responses were bilaterally present in of them. conclusion: in our study nse value over than ng ml at h was predictive of poor neurological outcome after cardiac arrest. nse may prove to be a useful marker in patients with present n responses, possibly limiting the duration of hospitalization by introducing therapeutic limitation or withdrawal of support. physicians assessment of prognosis in icu patients with brain introduction: outcome prediction in icu patients with severe brain damage is a difficult task with observed heterogeneity in physicians estimation. the aim of the survey was to evaluate the prognostic estimates and treatment recommendation of intensivists in real patients with various causes of severe brain damage. patients and methods: a web anonymous survey including a summarized clinical report of four patients who stayed in the icu was submitted to french intensivists. patient presented with prolonged hypoglycemic coma, patient with intracerebral hemorrhage, patient with central and extra pontine myelinolysis, patient with a brainstem hemorrhage. all these patients received full treatment in the icu and had a -month follow-up. physicians were provided with the four clinical vignettes including clinical history, brain imaging and other relevant exams (csf, eeg,…), evolution of symptoms within the first days of the icu stay. they had to estimate -month outcome using modified rankin scale (mrs) where a score from to was considered as a good outcome and to as a poor outcome. they had to provide a recommendation about care among the following-full treatment, care limitation, care withdrawal. results: physicians completed the survey. there were ( . %) female. ( %) respondents were residents and ( . %) had a > -year of experience. patients and had a good -month outcome with mrs and mrs respectively while patients and had a poor outcome, both with mrs . correct prognosis estimations were ( %), ( . %), ( %) and ( . %) in patients to respectively. care limitation or withdrawal was recommended by ( . %), ( . %), ( %) and ( %) respondents in patients to respectively. of interest, care withdrawal was recommended by ( . %), ( . %), ( . %) and ( . %) respondents in patients to respectively. univariate analysis did not display any factor related with a good prediction of prognosis. conclusion: in this study, overall predictions were pessimistic with important variations among respondents. although decisions to withdraw life sustaining care were relatively low with regard to estimated prognosis, both inappropriate care limitation leading to self-fulfilling prophecies and unreasonable prolonged life supportive care could result from these estimations. introduction: organ harvesting is a national priority because of the shortage of organs, responsible each year for the lengthening of transplant waiting lists. among the identified potential donors, the main cause of non-harvesting is the refusal of organ donation (od), which exceeds % in france and % in paris area. patients and methods: in a network of hopitals, each procedure on a potential donor by the donor co-ordinator is recorded in a report. after selection of the reports with interviews with relatives about od between and , the data in the reports were collected and a multivariate logistic regression was performed to identify the factors associated with the refusal. results: reports with interviews about od was found. the overall opposition rate is . %. among the children ( . % of cases) the opposition rate is . %. among adults, ( . %) expressed their will about od during their lifetime, with an opposition rate of . % and for the ( . %) of them who never expressed their will, the opposition rate is . %. the factors associated with opposition in multivariate analysis are presented in table . when the deceased had never expressed their will, the reasons given by the relatives to justify the refusal are specified in . % of the reports. these are religious grounds ( %), cultural grounds ( %), respect for physical integrity ( %). in % of the cases, relatives believe that the deceased would have been opposed, and in % of the cases, they choose to refuse because they do not know the deceased's opinion. discussion: french law is based on presumed consent. despite this, it is noted that when patients had never expressed their opinion about od (and therefore had not refused it), the opposition rate reached . % and was comparable to the patients who had expressed themselves. conclusion: in our study, factors related to refusal of od are mainly related to the characteristics of the deceased (religion, culture, history of ethylism) and those of relatives (disagreement, presence of a spouse), but little to the way of doing the interview. however, there is a trend for less opposition when the interview is conducted during the day (between - and - ). on the other hand, when relatives first address the issue of od, the opposition rate is lower. introduction: french intensive care society guidelines and the claes-leonnetti law recommend that intensive care teams organize collegiate and multidisciplinary discussions regarding limitation and withdrawal of care decisions. these moments, coined ethical staffs in our unit, require freedom and safety of speech, which can be difficult to obtain when people are caught in hierarchical and or power relations. we sought to assess the representations, perceptions and opinions of icu personnel regarding ethical staffs. patients and methods: a questionnaire, developed by the icu psychologist, was distributed to the entire unit (secretaries, nurses, nursing auxiliaries, doctors) over a period of months. this -question questionnaire covered session organization and power relations between participants. results: among the questionnaires distributed in the icu, were retrieved and analyzed. medical function was associated by respondents with roles linked with power (leading, knowledge, decision, explanation) whereas paramedical function was associated with roles linked with care (perception, account, spokesperson) (fig. ) . regarding representations of decision making, nurses were considered as decision makers in cases ( %) and doctors in cases ( %). discussion: although ethical staffs are presented as a place where each opinion counts, stereotypes representation appear in the different roles assigned-on one side doctors are in charge of explanation and decision, and on the other side, nurses are taking care of patient's feelings and assume a role of spokesperson. these stereotypes correspond to gender stereotypes assigning women to positions of care, empathy and relationship, and men to more intellectual and leading skills. these gender stereotypes attest a hierarchy internalized by each one, as highlighted by social sciences and gender studies. conclusion: our results highlight the existence of a global idea, shared by the majority-doctors are decision makers and therefore are in a power relation regarding paramedical staff. this hierarchical relationship persists in this moment wished egalitarian (each opinion would count equally). these is a linkage between professional power relations and gender power relations, which show an association between doctor and masculine "qualities" and caretakers and feminine "qualities". these power relations are rarely acknowledged but could have a significant impact on the decision process of these meetings, and should be further investigated. results. despite the diary, % had a qspt score > , indicating a higher post traumatic disorders. patients ( %) presented a anxiety score > and patients ( . %) had a depression score > . these results underline the need of psychological support after the stay. conclusion: many survivors of intensive care unit reported a high level of psychological distress. it seems important offer at this patient a psychological support after an intensive care unit stay. most patients needs return in intensive care unit to understand some elements of hospitalization. actually, this support lack to screening and treatment this psychological morbidity. prevalence and description of the complications following a percutaneous coronary intervention for a myocardial infarction in non-cardiac critically ill patients: a retrospective single-center introduction: type myocardial infarction (mi) is an emergency, which immediate invasive strategy by a percutaneous coronary intervention (pci) is based on guidelines for cardiologic patients. conversely, the invasive strategy remains uncertain for patients hospitalized in the intensive care unit (icu) for a primary non-cardiac disease with mi as a complication, given the ischemic and hemorrhagic risks. we aimed to assess the prevalence of-and describe the major adverse cardiac and hemorrhagic events occurring in the icu after an invasive strategy by pci in this context. we conducted a retrospective single-center -year ( - ) study. all the consecutive icu patients with a suspected mi undergoing a coronarography were screened. patients treated with an invasive strategy (pci performed within days of mi) were included. patients hospitalized in icu for cardiac disease were excluded. the major adverse cardiac events (mace) were defined as post-procedure events occurring in the icu, including death from cardiovascular causes, mi recurrence, need for emergent revascularization and stroke. the major adverse hemorrhagic events (mahe) were defined as post-procedure events occurring in the icu, according to the bleeding academic research consortium. results: icu patients suspected of mi underwent a coronarography. patients ( %) had significant coronary lesions. twelve patients were excluded-tri-truncular coronary involvement (n = ), delayed procedure (n = ), cardiogenic shock (n = ). patients were included ( men, years [iqr - - - ], patients mechanically ventilated, patients with sepsis septic shock, median sofa score at the time of mi [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ). a pci was performed during the first day after diagnosis of mi in patients ( %) (median time- day [iqr - - - ]). a mace occurred in patients ( %), including stroke (n = ) and mi recurrence without revascularization (n = ). no patients deceased from cardiovascular causes in the icu, neither at months post-procedure (table ) . a mahe occurred in patients ( %), of whom had a mace. altogether, the prevalence of major adverse cardiovascular events combining mace and mahe was . ( % ci . - . ). there was no difference between septic and non septic patients regarding the prevalence of mace or mahe. the prevalence of adverse cardiovascular events after an invasive strategy by pci is high in non-cardiac critically ill patients with mi. larger studies are needed to determine which patients may benefit from this procedure. introduction: resuscitated cardiac arrest (ca) lead to immune alteration including lymphopenia, decreased monocyte hla-dr (mhla-dr) expression and dysregulated production of cytokines. in a recent multicenter randomized clinical trial, we tested the hypothesis that cyclosprine a (csa) would limit organ failures following out-of-hospital cardiac arrest (ohca). in a substudy, we aimed to determine the influence of csa on ohca-induced immune dysfunction. this study is a predefined substudy of the randomized cyrus trial (cyclosporine in ca resuscitation). patients with non-shockable ohca randomly received either an intravenous bolus injection of csa ( . mg kg) at the onset of advanced cardiovascular life support (csa group) or no additional intervention (control group). patients from the coordinating center were sampled at admission (d ) and at h (d ). complete blood count, cd + lymphocytes count and mhla-dr were evaluated by flow cytometry. serum levels of il- , il- , il- , il- and tnf&# + were measured by elisa test on frozen samples. results: a total of patients were sampled- patients from the csa group and from the control group. the characteristics of the patients, including resuscitation data, were also similar between the two groups at admission. the severity of organ failure as assessed by the sofa score at admission was similar between groups. all patients introduction: critically ill patients experience major insults that lead to increased protein catabolism and a significant loss of lean body mass with an impact on weaning from the ventilator and muscle recovery. in critically ill patients, severe and persistent testosterone deficiency is very common after icu admission. administration of testosterone may induce skeletal muscle fiber hypertrophy and decreases protein breakdown. the aim of this work is to assess testosterone levels in critical ill patients and to evaluate the safety of testosterone gel administration. this is a single center study realized in a university icu of beds. total testosterone levels were measured in critical ill men with at least one organ dysfunction with sofa > . the study drug was androgel, a formulation of % testosterone in an alcohol-water gel, approved by the ansm for treatment of hypogonadism in men. androgel was applied to the abdomen, shoulders or upper arms once a day at the same time to dry and intact skin during icu stay. the daily dose was mg in men and mg in women daily. patients with history of prostate or breast cancer or psa > ng ml were excluded. results: total testosterone levels were measured in men. median length of stay at the time of measurement was days in icu and days in the hospital. plasma testosterone levels were low in all but patient. median testosterone level was ng dl (normal values - ng dl). testosterone levels were not correlated with score sofa or length of icu stay. we found a moderate positif correlation between testosterone levels and length of hospital stay (r = . =). testosterone gel was administered in men and in women. in these patients, the median score sofa was , icu death occurred in patients ( % icu mortality), median length of ventilation was days and median length of stay in icu days. all patients received mechanical ventilation and vasoactive treatment. patients needed renal replacement therapy. androgel was well tolerated. no ischemic cardiovascular events were described. there was no application site reaction or acne. median length of testosterone gel administration was days. conclusion: critical ill patients have low testosterone levels. testosterone gel may be safely administered during the acute phase in icu. randomized clinical trials are needed to evaluate the impact of testosterone gel on physical performance. introduction: stroke is the leading cause of physical disability and the second leading cause of death worldwide. two thirds of all strokes occur in developing countries and is increasingly a public health problem. the aim of this study was to evaluate the epidemiology of strokes in oran, algeria in order to create a stroke registry. patients and methods: a cross-sectional study was conducted on all patients admitted for stroke at the oran chu between january and september . sociodemographic data, modifiable and nomodifiable risk factors, type of stroke, degree of disability, severity scores (glasgow and nihss) were studied. the spss software, log rank test, was used for data analysis and statistical testing as well as kaplan-meier for survival studies. results: a total of stroke patients were enumerated, aged - years (mean ± sd = . ± . ), . % had an ischemic stroke and % had a haemorrhagic stroke. % of the patients were men and % of the women. high blood pressure, diabetes, emboligenous heart disease and smoking were the most common risk factors. intra-hospital mortality was . % and the overall survival rate at days was %. conclusion: this epidemiological study demonstrates that strokes at oran hospital may be similar to other locations. however, it seems necessary and useful to design a continuous patient registration system. introduction: the prevalence of hyperosmolar states and the relationship with mortality nevertheless remain unquantified and not objectively demonstrated. the aim of this work is to determine whether hyperosmolarity is a prognosis factor, and to assess the impact of hyperosmolarity on the evolution of patients. patients and methods: this is a retrospective descriptive and analytical study performed at the medical intensive care unit at the university teaching hospital ibn rushd in casablanca on the cases admitted during year. we noted epidemiological, clinical, biological and evolutionary parameters of all the patients and divided them into two groups according to their osmolar states, the first non-hyperosmolar group with plasma osmolarity of less than mosm l, called the control group and the second hyperosmolar group, plasma osmolarity greater than or equal to mosm l. results: patients were included. the first group comprised patients ( %) and the second comprised patients ( %). the two groups did not differ significantly about sex and age. hyperosmolar patients had more diabets . %. patients in the two groups did not show significant differences in clinical outcomes, including apache ii and saps ii scores. significant differences are reported between the two groups, in natremia, creatinemia, liver transaminases. the plasma osmolarity was significantly different between the two groups with a mean in the control group of . ± . mol l while in the hyperosmolar group it was . ± . mosmol l (p = . ). the prevalence of hyperosmolar states in the study was % with % mortality. in the control group % were intubated-ventilated + . % received vasoactive drugs and . % received antibiotic therapy. in the control group + %of the patients were complicated by nosocomial infection, . % by septic shock and % diseased by thromboembolic complications. the deceased subgroup used intubation artificial ventilation in . %, vasoactive drugs in %, and antibiotic therapy in . %. in the surviving subgroup, . % only contracted the nosocomial infection. in the subgroup died . % are of mixed hyperosmolar type + . % hyperglycemic hyperuremic + . % hyperglycemic hypernatremic type. conclusion: hyperosmolar states are an independent a prognosis factor. intubation and ventilation, vasoactive drugs and antibiotic therapy increases considerably in hyperosmolar states. furthermore, it induced serious complications as nosocomial infections and septic shocks that further aggravate the prognosis even within hyperosmolar states. introduction: hyperthermia represents a major life-threatening medical emergency, and is also one of the leading causes of death in young athletes worldwide. its incidence is rare and little understood, but its mortality is on the rise. the objective of this study was to describe the population of patients admitted for exertional hyperthermia in martinique and guadeloupe and to determine the prognostic factors. patients and methods: retrospective and prospective study, including all patients admitted for exertional hyperthermia in both emergency and resuscitation services in martinique and guadeloupe from january to june . results were expressed as mean ± sd or %. results: in years, patients were observed (age- ± , men and women), the main antecedents of which were- hypertension, chronic oh, psychoses, stress hyperthermia. ( %) of the patients had seizures initially. the pre-hospital management was < min. nevertheless, ( %) patients were admitted to icu due to organ failure (neurologic %, hemodynamic %, liver %). the progression was favorable, deaths, including fulminant hepatitis and multi-visceral failure. the average length of stay in intensive care units was days (± ). conclusion: despite considerable preventive measures, stress hyperthermia represents a major problem within the military, soldiers and other athletes, with a mortality rate about % in most published series. the most effective method is immersion in ice water. there is an urgent need to provide the region with a clear preventive policy, including a relief action plan, training for doctors, athletes and other health professionals at risk of hyperthermia. chapoutot anne-gaëlle , leteurtre stéphane , chamouine abdourahim ( ) . the university hospital of lille is a pediatric center including several itecus in its pediatric hematology or gastrology departments, and more recently in its pediatric surgical department. moreover, there are - itecu extra-beds within the - bed pediatric intensive care unit (ivecu). the hospital of mayotte has no pediatric ivecu but a polyvalent one for adults, which receives children when necessary, as well as a bed itecu. the aim of this study was to describe prospectively the pediatric population which was admitted in the itecus of lille and mayotte over a one-year period from june to may . patients and methods: in this twin-center, prospective and observational study, data were collected for each patient admitted during the test period in itecus of both lille and mayotte pediatric hospitalsgeneral information about the patient, characteristics of each stay, severity scores on admission, type of treatments implemented, the report of the stay and patient's evolution. a standard declaration was made with an authorization granted by the local commission on informatics and liberty (french commission informatique et liberté, cil). results: during the course of the study, about children were admitted in each center. the collected data allow to describe and compare both populations in terms of severity of each patient's condition. this study based on a very large cohort has permitted to compare the population of a regional hospital with that of a university hospital and to demonstrate that a health-care provision including a pediatric intensive care unit is needed on mayotte island. introduction: simulation in intensive care is an innovative method for teaching. respiratory settings are responsible for some morbi-mortality of our patients. for this reason we develop a simulator of artificial ventilation (simva) and virtual patients. mathematical model resolved differential equations of chest and lung movements in order to match with a clinical data base. the goal of this study was to evaluate and compare virtual patients respiratory mechanic with the results of different protocols of ventilation from large randomised controlled trial-arma ( ) and express ( ). patients and methods: virtual patients had ards, and were defined by different thoracic and pulmonar compliance, total resistance, lung volumes, pressure-volume relation, and pressure and volume recruitment coefficients. ventilatory protocols were high versus low vt (arma study) and max versus min distension according to pep (express study). each virtual patient was titrated on the simulator with the protocols. respiratory frequency was set around cycles minute and adapted to protocols. respiratory mechanic after titration was recorded and compared to results of the studies. results: results are summarised in the table-the difference between virtual and real patients were not significant. vm l/min . ( . ) . ( . ) . ( . ) . ( . ) . ctp: tharacopulmanar compliance (ml/cmh o) discussion: inspiratory plateau pressure and thoraco-pulmonary compliance were able to change according to pep or vt settings within the same range as the large rct studies. mathematical model of recruitment was adapted to create many different results while pep was titrated according to respiratory mechanics with the express protocol. conclusion: simulation of artificial ventilation with a software can be realistic and might be an interesting pedagogical tool to teach interactively and repetidly ventilatory settings and respiratory mechanics interactions in ards without any risk for the patient in our units. introduction: expiratory flow limitation (efl) has previously been investigated in ards patients on zero peep by using negative expiratory pressure (nep) technique on tidal breath. in ards patients with efl peep improved oxygenation from intrinsic peep homogenization rather than lung recruitment. the nep technique is no longer available. as efl should reflect airway closure it is important to assess it. we described a new technique to assess efl. patients and methods: thirty-nine ards patients ( mild, moderate, severe) were investigated at peep and . they were intubated, mechanically ventilated (evita xl) in volume controlled mode (tidal volume ± ml kg predicted body weight) in the semi-recumbent position. airway pressure and flow measured proximal the endotracheal tube were continuously recorded (biopac ). we measured respiratory mechanics by the occlusion technique at each peep and recruited lung volume between peep and by using low flow inflation method associated with measurement in change in end-expiratory lung volume. for the latter, patient was manually disconnected at the end of baseline tidal inflation downstream pneumotachograph to atmosphere til zero flow, then reconnected at previous settings. efl was assessed offline by superimposing flow-volume loops of disconnected and baseline breath. efl was defined if no change in flow occurred over all or part of the disconnected expiration as compared to the baseline breath and no efl (nfl) if any increase in flow during the expiration was present (fig. ) . the percentage of the tidal volume involved in efl was measured. results: efl was present in patients ( %) over % of the tidal expiration. patients with efl had significant higher body mass index ( ± vs. ± kg m , p < . ) and totalpeep at peep ( ± vs. ± cmh o, p < . ) than nfl patients and tended to be more hypoxemic. at peep efl patients had a significant better compliance ( ± vs. ± ml cm h o, p < . ) with no change in recruited lung volume ( ± vs. ± ml) and tended to be more hypoxemic than nfl patients. mortality at icu discharge was % in efl versus % in nfl (p = . ). conclusion: measurement of efl is feasible without the nep technique. at higher peep ards patients with efl markedly improved compliance of the respiratory system not related to lung recruitment. further studies are required to better understand efl in ards patients and to assess its impact on patient outcome. limiting factor being carbon dioxide accumulation and hypercapnic acidosis. extra corporeal carbon dioxide removal (ecco r) intervenes by maintaining ph and pco within physiological ranges. this combination is called ultra-protective ventilation. we report our experience with ecco r in ards and non ards patients with a focus on feasibility and safety. patients and methods: from june to july all patients who have undergone ecco r in our icu were included consecutively and prospectively. venovenous ecco r was used through a dual lumen venous catheter (femoral or jugular). results: nineteen patients underwent ecco r for a total of sessions. ecco r was implemented through a dual lumen venous catheter (femoral or jugular) with different devices-hemolung respiratory assist system ® (alung) (n = ), ila activve ® (novalung) (n = ) and prismalung ® (prismaflex system) (n = ). sessions were (iqr . - . ) days long. catheter diameters were fr (n = ), fr (n = ), fr (n = ) and fr (n = ). thirteen patients suffered from ards and had non ards indications for ecco r, including ultraprotective ventilation. tidal volume decreased during ecco r from . (iqr . - . ) to . (iqr . - . ) ml kg of predicted body weight (p < . ) while ecco r allowed maintaining of ph and pco within acceptable range (fig. ). driving pressure decreased from (iqr - ) to (iqr - ) cm h o (p < . ). the main adverse effect was thrombocytopenia ( patients). six selected patients had no anticoagulation during ecco r because of high bleeding risk. discussion: ultra-protective ventilation was achieved with a decrease of tidal volumes (vt < ml kg) and positive pressures. few data on ecco r are available in patients at high risk of hemorrhagic complications, we report here a subgroup of patients who underwent efficiently ecco r without anticoagulation. six patients underwent ecco r for non ards indications, of them had no structural damages to the lungs which has never been reported and eccor allowed implementing ultra-protective ventilation with no major adverse effect. we report our experience on ecco r for ards and non ards indications. ultra-protective ventilation (vt < ml kg) was safe and feasible. the impact of general practitioners consultation on ards complicating community acquired pneumonia donval ulysse , tadie introduction: community-acquired pneumonia (cap) is a potentially severe infection that results in numerous general practitioner (gp) visits and hospital admissions each year. cap is also the most frequent single cause of acute respiratory distress syndrome (ards). risk factors for development of ards in the course of cap are not clearly defined although prognostic factors associated with mortality have been extensively studied. gp visits, as an early diagnosis and earlier access to antibiotics prescription could significantly affect the course of cap. the aim of the present study was to evaluate the impact of general practitioners consultation on ards complicating cap admitted to our icu. patients and methods: we retrospectively reviewed the medical records of all patients aged over years admitted between october , and december , , for ards complicating community acquired pneumonia with a pao fio ratio < mmhg after at least h of lung protective mechanical ventilation (mv). ventilatory modalities for ards had been protocolized over the study period as our icu was recruiting patients for two consecutive multicenter trials (acurasys and proseva). consequently, the protective ventilatory strategy used in these two clinical trials was applied to every patient with ards. patients were divided into two groups according to whether or not they visited a gp before icu admission. : patients were admitted for ards complicating cap. patients ( %) had visited a gp before admission in icu (gp +) and did not (gp-). analysis of demographic data, respiratory microbiology patterns, ards severity at admission did not show any differences between the two groups. sofa score at admission was significantly higher in gp-compared to gp + patients ( . ( - ) vs. . ( - ) respectively + p = . ) although respiratory sofa scores were not different ( ( - ) vs. ( - ) respectively + p = . ). ( %) gp-( %) and ( %) gp + patients presented septic shock at icu admission (p = . ). multivariate analysis found that gp consultation ( . [ . - . ] + p = . ) with antibiotics prescription ( . [ . - . ] + p = . ) were associated with decreased mortality at day ( fig. ) . in patients admitted to our icu for ards complicating community acquired pneumonia, gp visits prior to icu admission was associated with a better outcome. the beneficial effect may be due to earlier antibiotic prescription which could significantly lowered severe infection and septic shock. introduction: optimal peep level during ards remains controversial because of its beneficial and adverse effects. the optimal level of recruitment and its effect on oxygenation are not well defined and no technique is currently validated. the aim of our study was to evaluate the correlation between the recruited pulmonary volume estimated by a new technique (crf inview ® ) and the evolution of pao as well as the respiratory and hemodynamic tolerance of the application of an increasing levels of peep . patients and methods: a prospective, monocentric study that will last years (january -january ), taking place in the intensive care unit at the military teaching hospital of tunis and including patients if they met standard criteria for ards (berlin criteria). the main criterion for judgment was the correlation between the recruited pulmonary volume estimated by a new technique (crf inview ® ) and the evolution of the pao after application of three increasing levels of peep ( - - ). the other secondary criteria were the respiratory and hemodynamic tolerance of the application of increasing levels of peep measured by the picco ® technique. aimed to investigate the concordance between the onset of three vae tiers and valrti, and their impact on outcomes. we performed a retrospective analysis of prospectively collected data from patients requiring mechanical ventilation for more than days in a -bed mixed icu of a tertiary university teaching hospital, between january and december , . vat and vap episodes were assessed by prospective surveillance of nosocomial infections, according to the american thoracic society criteria. vae were identified retrospectively, according to current cdc definitions. the agreement between vac, ivac, pvap and valrti was assessed by k statistic. the impact of vae and valrti on duration of mechanical ventilation, icu and hospital length of stay and mortality was also assessed for the first episode of vat and vap. results: we included patients ( ventilator days). vap ( . per ventilator-days), vat ( . per ventilator-days) and vae ( . per ventilator-days) were diagnosed. there was no agreement between vat and vae and the agreement was poor between vap and vac (k = . , % ci . - . ), vap and ivac (k = . , % ci . - . ) or vap and pvap (k = . , % ci . - . ). patients who developed vat, vap or vae had significantly longer duration of mechanical ventilation, icu and hospital length of stay, compared to patients who did not, with similar mortality rates. conclusion: vae are not relevant for vat diagnosis and have low agreement with vap, despite their negative impact on ventilation duration, icu and hospital length of stay ( fig. ) . the introduction: post-operative pneumonia (pop) is a frequent and severe complication of major lung resection surgery. in , we changed our surgical antibioprophylaxis protocol from cefamandole to amoxicillin-clavulanate and observed a significant decrease of pop incidence and mortality. in , we additionally implemented in the respiratory intensive care unit (ricu) an antimicrobial stewardship program based on a local antimicrobial guideline and a weekly multidisciplinary review of all antibiotic therapies by ricu physicians, infectious diseases specialists and microbiologists. our objectives were to describe our current epidemiology of severe pop and to assess the quality of antibiotic prescriptions. patients and methods: all patients with severe pop occurring within days after lung resection between january and december were included. we collected data on clinical presentation, results of microbiological investigations, antibiotic regimen and outcomes. the quality of antibiotic use was assessed using indicators previously validated in the literature. results: over patients who underwent major lung resection in our center, matched criteria for severe pop and were included. most were males (n = , %). the median age was years (minimum- + maximum- ). most patients had chronic obstructive pulmonary disease (n = , %) and ( %) a history of non-pulmonary cancer. the resection consisted in lobectomy in % (n = ). the median length of stay in ricu was days ( + ), and -day mortality was % (n = ). respiratory microbiological samples were obtained in all patients, in most cases invasively per bronchoscopy ( %). microorganisms were cultured at a significant level in ( %) patients. predominant species were enterobacteriacae ( %), haemophilus influenzae ( %), staphylococcus aureus ( %) and pseudomonas aeruginosa ( %). microorganisms were sensitive to third generation cephalosporins in ( %) and to piperacillin-tazobactam in ( %). in patients treated empirically, antibiotics were prescribed according to the guideline in % ( ). in documented pop, empiric antibiotics were active against documented micro-organisms in ( %), and were correctly changed to pathogen-directed therapy in ( %). the median duration of antibiotics was of days ( + ). conclusion: ten years after implementation of amoxicillin-clavulanate as surgical antibioprophylaxis, the proportion of enterobacteriacae increased. the -day postoperative mortality rate remained below %. we report high adherence to the guideline for the choice of empirical therapy and treatment duration. the rate of de-escalation to pathogen-directed therapy could however be improved considering the high rate of bacteriologically-documented pop. resistance of pa has reduced between both periods from % to % (p < . ) for ceftazidim, from % to % (p < . ) for cirpofloxacin and from % to % (p < . ) for imipenem. nevertheless, among the cases, the p period did not change the risk of developing an infection (rr = . , ci % . - . ), a vap (rr = . , ci % . - . ), a septicemia (rr = , ci % . - . ) or the mortality rates (rr = . , ci % . - . ). conclusion: colonization and infection with pa are risk factors of increased mortality rates and alos in icu. an antibiotic stewardship program allows to reduce the incidence of patients having a positive sample with pa, and the antibiotic resistance of pa strains, without reducing the infection rate of these patients. impact of a local care protocol on the duration of antibiotic therapy in community-acquired peritonitis: years of experience introduction: the use of antibiotics is a major public health, economic and ecological challenge. in , a french national warning plan was created to manage the use of antibiotics. it advocates monitoring of the prescription of antibiotics and the implementation of measures to assess professional practices. the great majority of guidelines concerning the duration of antibiotic therapy in community-acquired peritonitis are based on studies with low level of evidence. the objective of this study is to evaluate the implementation of a standardized operational report (sor) with a local antibiotic protocol in the management of community-acquired peritonitis at our institution. patients and methods: this is a monocentric, prospective cohort study-before and after the establishment of the sor. the primary endpoint is duration of antibiotic therapy. secondary endpoints are length of hospitalization, infectious complications, mortality, and changes in local bacterial ecology. we have also evaluated retrospectively these different criteria on cohort was constituted since . results: a total of patients were enrolled from january to june and patients from may to may . the duration of antibiotic therapy was decreased by to days in localized peritonitis (p < . ) and to days in generalized peritonitis (p < . ) (figure) . however, the compliance to the protocol was only %, which leads to an increase in the duration of antibiotic therapy and hospital stay when not used (p < . ). the hospital stay decreased from to days in the localized peritonitis (p < . ). amoxicillin clavulanic acid (amc) is the most used antibiotic with an efficiency of %. there was no impact on morbidity and mortality when amc was inadequate. the bacterial ecology was not modified, the rate of extended-spectrum beta-lactamase (esbl) producing enterobacteria (esble) was %. the use of a standardized antibiotic protocol reduced antibiotic therapy duration and hospital stay, particularly in localized peritonitis despite incomplete compliance to the protocol. to achieve full compliance, we need to continue the training of different physicians and continue the spread of the protocol. introduction: bacterial meningitis is an important public health problem because of its frequency and severity. they remain a major cause of mortality and morbidity in developing countries. the aim of our work is to establish the epidemiological characteristics and the prognostic factors . patients and methods: we did a retrospective descriptive and analytical study and we included all the patients admitted for severe meningitis for year in the medical intensive care unit of the university teaching hospital ibn rushd at casablanca-morocco. results: patients were included. the incidence of severe meningtis was . %, the mean age was years old and the sex ratio h f was , . , % were pneumococcal meningitis and % were tuberculosis in univariate analysis, factors influencing mortality significantly-the male sex patients with pulmonary tuberculosis as an antecedent.• a low glasgow score at admission. the presence of a neurological deficit arterial ph, mean (sd) arterial lactate, mean (sd) kidney disease-improving global outcomes chronic kidney disease guideline development work group members. evaluation and management of chronic kidney disease-synopsis of the kidney disease-improving global outcomes clinical practice guideline dramatic increase in venous thromboembolism in children's hospitals in the united states from antithrombotic therapy in neonates and children acute childhood arterial ischemic and hemorrhagic stroke in the emergency department childhood hemorrhagic stroke-an important but understudied problem emergency management of deeply comatose children with acute rupture of a cerebral arteriovenous malformation goulmane mourad -m.goulmane@hotmail.com annals of intensive care we recorded episodes of nosocomial infections-pneumonia (n = , . %), bacteremia (n = , . %), catheter related infections cri (n = , . %) and urinary infections (n = , . %). pathogens isolated were largely dominated by non-fermentent gram-negative bacilli (n = , . %)-acinetobacter baumanii (n = , . %) with % resistance to imipenem and tygecycline, pseudomonas aeruginosa (n = , . %) with . % resistance to ceftazidim and stenotrophomonas maltophila (n = ). other gram-negative bacilli were enterobacteries (n = ), which were wide-spectrum betalactamase secreting (n = ) and carbapenemase (n = ). gram-positive cocci were the second highest (n = , . %)-coagulase negative staphylococcus (n = ) which were resistant to methicilline ( %), enterococcus (n = ) which were resistant to vancomycin (n = , . %), staphylococcus aureus sensitive to methicilline (n = ) and streptococcus (n = ). candida was incriminated in cases of cri we report here that neonates had a reduction in hla-dr expression after cpb, and those with prolonged decreased hla-dr in the early postoperative period (day ) could represent a subpopulation at greatly increased risk of later ni. if confirmed in a larger cohort of patients, our findings could indicate that hla-dr may be a useful biomarker of immunosuppression after cpb in neonates. non-traumatic hemorrhagic stroke (nths) in comatose children: epidemiological features and clinical presentation conclusion: compared to normobaric ltot the fio is lower during niv with the same o flow. compensation for intentional and nonintentional leaks and so an increase of air flow despite a constant o input might explain this. in intermediate care the use of hv for niv may be interesting alternative in which case the clinician must keep in mind that the fio decreases compared to standard oxygen therapy. concerning home usage we hypothesize that this partial removal of o treatment could contribute to the poor results of niv in chronic copd. introduction: in february , we opened a beds-post icu rehabilitation center (service de rééducation post réanimation, «srpr»), dedicated to weaning from mechanical ventilation and global post icu rehabilitation. objectives-description of the characteristics and main outcomes of the patients admitted over the first year of activity. patients and methods: retrospective analysis of data extracted from the medical files. results: patients were admitted times in the unit over its st year, from different icus (median duration of stay in the icu . days (iqr - )). % were ventilated ( % with niv). % had a tracheostomy. % had icu acquired weakness + % were able to walk. an underlying chronic respiratory disease was present in % of cases. % were obese. difficult weaning was found to have one or several respiratory components in % of cases (including post surgery diaphragmatic paralysis), cardiac in %, neurologic in %. significant complications occured in % of cases. median duration of stay was . ( - . ) days. ten patients died in the unit, patients were re-transferred in the icu, where of them died. over half of the patients were discharged at home, in a rehabilitation unit (ssr) or in a hospital ward awaiting a rehabilitation bed. the remaining %, that still needed some form of medical or surgical care were discharged in the ward (fig ) . in intention to treat, successful weaning from invasive ventilation was obtained in % of patients. of the patients discharged alive from the unit after completing the rehabilitation program (n = ), % were completely weaned from mechanical ventilation, % were discharged with niv or cpap + patients ( %) were considered not weanable from invasive ventilation + decanulation of tracheostomy was obtained in % of cases + % of the patients could walk. conclusion: srprs offer a new concept of care for difficult to wean patients, with promising results. introduction: scarce data about patients with prolonged weaning from the mechanical ventilation are available in the literature. patients without successful weaning days after their first weaning attempt were classified in the group of the weaning according new definition (wind) classification ( ) . we here describe specific data concerning weaning and hospital evolution of group patients included in this prospective cohort. among the patients included in the wind study, were classified in the group . additional data concerning comorbidities, cause of weaning failure and hospital evolution were collected for ( %) of these patients. results: these patients had median [interquartile range] duration of invasive mechanical ventilation of [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days and [ ] [ ] [ ] separation attempts. etiology of icu hospitalization was medical in ( %). they had a copd in ( %), hearth disease in ( %) and immusoppression in ( %). we noticed a mean saps ii of ± , a mean sofa d of ± and d of ± . tracheostomy for weaning was performing in ( %). at the end of their follow-up, ( %) were still alive- ( %) were still tracheostomized, still intubated and ventilated, ( %) treated with vni and ( %) were extubated (or decannulated) and breathed without assistance. among the patients still tracheostomized at the end of the follow-up, ( %) were still ventilated (permanently for of them, and partially for ) and ( %) had spontaneous breathing through their tracheostomy. these patients had a total icu length of stay of days. the destination at discharge from the icu is known for only of the survivors- ( %) in medical ward, ( %) in intermediate care units, ( %) in sub acute care, ( %) in icu and in surgical ward. conclusion: a third of the patients of the wind study classified in group and with available additional data died in hospital in months following intubation. at the end of the follow-up, % had spontaneous breathing without assistance, and % were still tracheostomized. among these tracheostomized patients, one third still required mechanical ventilation. ( )-béduneau, g., pham, t. and co ( ) . epidemiology of weaning outcome according to a new definition. the wind study. ajrccm, ( ) , - . introduction: copd patients have often polyglobulia because of associated hypoxemia especially in patients at the stage of chronic respiratory failure. we recently reported that anemia was present in % of patients with severe aecopd admitted to icu without impact on short-term prognosis. the aim of the present study was to assess the long-term impact of haemoglobin (hb) levels on outcomes of aecopd patients. patients and methods: in a prospectively collected database including consecutive patients admitted between and for aecopd in our icu. long-term status of patients following the first icu admission (surviving or deceased) has been verified by consulting the civil status registers. anemia was defined according to who criteria-hb < g dl in males + hb < g dl in females. long-term survival was assessed by kaplan-meier curve. results: the cohort included patients (median age , median ph . , . % males, niv as first ventilator mode in . %). anemia was observed in of the patients ( . %) with median haemoglobin levels at . and . g dl, in patients with and without anemia, respectively. anemia was associated with significantly lower years survival (log rank p = . ) (fig. ). the final model included age, saps ii score, comorbidities, home oxygen therapy, initial ventilatory mode, niv failure and haemoglobin levels. multivariate analysis identified age (or . per year + ic % . - . + p = . ), home oxygen therapy prior to exacerbation (or . + ic % . - . + p = . ), intubation at icu admission (or . + ic % . - . + p < . ), niv failure (or . + ic % . - . + p < . ), and haemoglobin (or . per decrease of g dl + ic % . - . + p = . ) as independently associated factors with years mortality . we conducted a prospective observational study including all patients who visited the sis during the last months. the collection of the usual anonymous demographic, medical and toxicological data was performed by the care-givers and social workers in charge of the drug users. data were declarative and no analytical confirmation was available except for the patients admitted in the icu. results discussion during months, drug users [f m sex ratio . + median age . years ( - ) + patients without resources ( %), without medical insurance ( %), unstable housing homelessness ( %)] visited the sis for drug injection or inhalation, representing , drug use including , inhalations and , injections by drug users day. drug users had no addictology ( %) or sociomedical ( %) follow-up. they were infected by hepatitis virus c ( %) and or hiv ( %). they declared to continue injecting in the public space ( %), sharing material ( %), and needles syringes ( %). the injected inhaled drugs in the sis were skenan ® (morphine, . %), crack ( % including injections), methadone ( . %), buprenorphine ( . %), heroine ( . %), and cocaine ( . %). these drugs were self-administered by polydrug users declaring concomitantly consuming crack ( . %), illicit morphine ( . %), cocaine ( . %), ethanol ( . %), cannabis ( . %), heroin ( . %), illicit methadone ( . %), benzodiazepines ( . %) and illicit buprenorphine ( . %). forty-five patients required a paramedical intervention in the sis resulting in calls to the emergency department and hospital admissions including transfers to the icu in relation to opioid overdose. no cardiac arrest and no death occurred. conclusion: sis visit for recreational drug self-administration rapidly becomes popular among drug users. illicit morphine (skenan ® ) glycemia (mmol/l) . ( - ) . ( - )ketones in the effluent liquid (g/l) . ( . - . ) ( - ) patients and methods: physiological tracings were recorded from the standard monitoring system (intelliview mp philips), using a dedicated network and extraction software (synapse v , ltsi inserm u ) that enables photoplethysmographic recordings from oximetry monitoring at a native resolution of hz. raw data were subsequently stored on a dedicated local server, before anonymization and analysis. all consecutive patients were recorded for a -hours period during the -hours following icu admission. all measurements were recorded with the patient laying supine, with a ° bed head angulation. physiological recordings were associated with metadata collection by a dedicated research assistant.hrv parameters defined in a previous study were derived using kubios hrv premium ( introduction: preventing post liver transplantation (lt) hepatic artery and portal vein thrombosis is challenging and includes enoxaparin administration. enoxaparin pharmacokinetics (pk) has not been investigated in children following lt. between-subject variability and critical illness may alter pk, leading to the risk of subtherapeutic exposure. patients and methods: clinical, biological and kinetic data were retrospectively collected in a single pediatric intensive care unit center from january to july . we described an enoxaparin pk model in children the first week following the lt. anti-xa activity timecourses were analyzed using a non linear mixed effects approach with monolix version r. results: anti-xa activity time-courses were well described by a one-compartment open model with first order absorption and elimination. body weight prior the surgery (bwpreop) and the related postoperative variation (bw(t)) were the main covariates explaining cl and v between subject variabilities. parameter estimates were cli = cltyp*(bwpreop ) + vi = vtyp*(bw(t) ) + where typical clearance (cltyp) and typical volume of distribution (vtyp) were . l h − and . l, respectively. standard dosing regimens of iu kg h were insufficient to reach the target range of anti-xa activity of . to . iu ml. specifically, children ( %) did never attain the target range during the whole period of treatment and all children were at least once under dosed. according to the final results, we simulated individualized dosing regimens within h following the first administration. more than iu kg h are suggested to reach the target range of anti-xa activity of . to . iu ml from the first day. standard enoxaparin dosing regimens is not appropriate to reach the target in pediatric liver transplantation patients. enoxaparin pk modeling should help the physician to achieve the target range from the initial dose and during the maintenance doses. higher dosing regimens, especially in youngest children are suggested to achieve the prophylactic target range. pharmacokinetic analysis of unfractionated heparin in critically ill children during extracorporeal membrane oxygenation: do we achieve the target? introduction: preventing thrombosis in children under extracorporeal membrane oxygenation (ecmo) requiring unfractionated heparin administration. unfractionated heparin pharmacokinetics (pk) has not been well investigated in children under ecmo. we described the unfractionated heparin dosing regimens and resulting anti-xa activities in children with ecmo. patients and methods: this is a single center retrospective study from march to september . were included children (< years old age) who were under ecmo for refractory hemodynamic failure related to (i) myocarditis or (ii) septic shock. anti-xa activity timecourses were analyzed using a non linear mixed effects approach with monolix version r. results: a total of children were included (septic shock, n = + myocarditis + n = with a median age of months ( - ), a median weight of . kg ( . - ) and median admission pelod- score of ( - ). bleeding occurred in children and thrombosis in . an initial bolus of unfractionated heparin ranging from to iu kg was infused and then continued by continuous perfusion with an initial dosing ranging from iu kg h to iu kg h. a total of anti-xa activity measurements were performed between h empirically antibiotics for these patients with severe infection may be recommended. introduction: prognosis of allogeneic hematopoietic stem cell transplant (hsct) recipients admitted to icu has improved with advances in hsct procedures and critical care management, but also with evolution in icu triage policy. our aim was to describe the outcome of hsct recipients admitted to icu according to a wide admission policy. patients and methods: retrospective multicenter study including all consecutive allogeneic hematopoietic stem cell transplant (hsct) recipients admitted to saint-antoine hospital medical icu, paris, france from to january to april . admissions were identified through a systematic review of icu database using icd- codes z and t . data were extracted from medical charts. qualitative and quantitative values are expressed as number and percentage, and median and interquartile range, respectively. comparisons between groups were performed using fisher's exact test and mann-whitney test for qualitative and quantitative variables, respectively. a p-value < . was considered to be significant. results: one hundred seventeen patients- men ( . %), median age [ - ] years-were included in the study. underlying hematological malignancies were: acute myeloid leukemia (n = , . %), myelodysplastic/myeloproliferative neoplasms (n = , . %), acute lymphoid leukemia (n = , . %), lymphoma (n = , . %), other ( . %). complete remission was achieved before hsct in ( %) patients. forty-nine ( . %) patients underwent myeloablative conditioning regimen and ( . %) received haploidentical grafts. twenty-eight ( . %) patients experienced disease relapse after hsct and ( %) graft versus host disease prior icu admission. median saps ii was and sofa score at day one [ - ]. the icu, hospital and -day mortality rates were respectively . , . and . %. in univariate analysis, factors associated with -day mortality were: saps ii (p = . ), invasive mechanical ventilation (p < . ), vasopressors (p = . ) and renal replacement therapy (p = . ). mechanical ventilation was the only independent factor of -day mortality (or . - . ], p < . ) with mortality rate reaching . % and even . % among patients with uncontrolled hematological disease. conclusion: prognosis of unselected hsct recipients admitted to icu remains poor, particurlaly among those receiving mechanical ventilation, and even more if hematological disease is not controlled. these results suggest that the implementation of an icu triage policy determined both by intensivits and hematologists would be helpful to identify good candidates for icu admission. introduction: acute respiratory failure (arf) is a common event in patients with primary malignant brain tumors (pmbt). even if many factors (corticosteroid therapy, swallowing disorders) suggest a specific etiologic spectrum, few data are available regarding its precipitating factors. our first aim was to compare the causes of arf between patients with pmbt and those with other type solid tumors. our second aim was to identify, among pmbt, the factors influencing survival in icu. patients and methods: bicentric case-control study from march to may . patients with pmbt (cases, primary central nervous system lymphoma included) admitted for arf were compared to patients with other kind of solid tumors (controls). the reason for admission "arf" as well as the causes of arf was determined by three experienced respiratory physicians and were required for inclusion: a respiratory rate > cycles/min and a pao /fio < for patients in spontaneous breathing and only a pao /fio < for patients under mechanical ventilation. in both groups were excluded patients with metastatic solid tumors, benign tumors or tumors with more than years of complete remission, recent post-operative patients, and patients with other immunodeficiency. results: a total of cases and controls were included. main patients' characteristics are reported in the table . acute infectious pneumonia was the leading cause of arf in both groups but was more frequent among cases ( vs. %, p < . ). cardiogenic pulmonary edema and exacerbation of chronic respiratory diseases were more frequents in controls ( vs. %, p < . ). pulmonary embolism was similar between the two groups ( vs. %, p = . ). among acute infectious pneumonia, pneumocystis pneumonia (pcp) and aspiration pneumonia were more frequent in cases ( vs. %, p < . and vs. %, p < . respectively). in multivariate analysis cancer progression (or- . %ic [ . - . ], p = . ), need for intubation (or- . %ic [ . - . ], p = . ) and respiratory rate (or- . % ci [ . - . ], p = . ) independently predicted icu mortality of pmbt patients. conclusion: in pmbt patients, the causes of arf differ significantly from other cancer patients. up to % of the admissions was related to preventable causes (pulmonary embolism, pcp) and a curable cause was identified in the majority of cases. our results suggest that pmbt alone is not a relevant criterion for icu recusal. introduction: drug intoxication is a common problem encountered in emergency departments. poisoning remains a major cause of hospitalization for young people, and that of the elderly is constantly increasing. objectives . determine the epidemiological characteristics of addicted patients . know the clinical manifestations of poisoning. patients and methods: a retrospective study of cases of acute poisoning recorded at the university hospital center chuoran between january and december was carried out. seizure on data processing by epi-info version . results: cases of acute poisoning, with an age ranging from to years. female patients predominated with %. people between the ages of and are the people most affected by poisoning. the nature of poisoning is varied. in this series, analgesics were found to be the leading cause of acute intoxication, with cases, % followed by psychotropic drugs ( %), benzodiazepines ( %), neuroleptics ( %), antiepileptics%) and antihistamines ( %). the majority of acute intoxications were managed within an average time of . ± . h with an interval between . and h. in % of cases the poisoning was asymptomatic, there were digestive manifestations in % of patients, % neurological, % cardiovascular and % respiratory. we deplore death in this series secondary to many drug poisoning. conclusion: acute drug poisoning is a common reason for admission to the emergency department of oran university hospital. the large number of drug families offered for sale, as well as the heterogeneity introduction: selective serotonin reuptake inhibitors (ssris) have been considered for their low toxicity comparatively to antidepressant agents. the present study aims to describe clinical features and prognosis of poisoning ssris. patients and methods: a retrospective study of patients admitted to our -bed teaching icu for acute ssris poisoning over a period of years from january to december . ssris poisoning was retained on a history of over dose ingestion, clinical signs and positive urine samples for ssris. results: thirty seven patients were collected, the middle age was ± years with a female predominance ( . %). a psychiatric history with depressive syndrome was noted in . % and a history of suicide in . %. paroxetine was the main invoked drug (n = ), followed by sertaline (n = ), then fluoxetine (n = ), venlafaxine (n = ) citalopram (n = ). the mean supposed ingestion dose was . mg. intoxication was pure in cases and associated with other drugs in cases-benzodiazepines (n = ), klippal (n = ), amisulpride (n = ), non-steroidal anti-inflammatory drug (n = ), prazin (n = ) and promethazine (n = ). neurological examination found drowsiness and mydriasis in % of cases (n = ), coma in . % (n = ), agitation (n = ), tremor (n = ), hyperreflexia (n = ), hypersudation (n = ), fever (n = ) and diarrhea in one patient. the qt was lengthened in five cases. treatment was symptomatic. five patients ( . %) required mechanical ventilation with average of ventilation duration of . h. all patients discharged alive the icu. conclusion: ssris poisoning is mainly manifested by serotonergic syndrome. evolution is favorable in the majority of cases. mechanical ventilation could be required. hemodynamic profile of shocks induced by dihydropyridine calcium channel blocker poisoning khzouri takoua introduction: acute calcium channel blockers (ccb) poisoning remains infrequent despite their increasing use. in our country, dihydropiridines are the most prescribed ones. very few works have studied the hemodynamic profile of acute dihydropyridines poisoning either by invasive means (right cardiac catheterization, transpulmonary thermodilution) or non-invasive (cardiac ultrasound). in this perspective, we carried out this study whose main objective was to illustrate the different hemodynamic profiles of shocks induced by dihydropyridine ccb poisoning. patients and methods: it was an observational retrospective study spread over months from st january to th december in a teaching toxicological icu, including all patients admitted for acute dihydropyridine ccb poisoning, who presented a shock and underwent right hemodynamic exploration.results: during the study period, ccb poisoning accounted for . % (n = ) of all the acute poisoinings requiring hospitalization in our intensive care unit. among them, had taken dihydropyridine which represents . %. four women aged of [ , ] were eligible. all the exposures were single-drug. the dihydropyridines involved were amlodipine in cases with a median value of supposed ingested dose (sid) of . mg and nicardipine in the other two ones, the median sid was mg. the delay of consultation was of . ± h after ingestion. gastrointestinal decontamination was performed in one patient with activated charcoal. the patients developed a shock within h, treated by initial vascular filling on average ml of crystalloids, noradrenaline alone in cases and with a combination of dobutamine in one patient. other adjuvant treatments (high dose insulin, calcium salts) have been used in all patients. their hemodynamic profile evaluation by right-handed catheterization swan-ganz was in favour of vasoplegia in cases with median values of systemic vascular resistances (svr) of dynes.s.cm- , of cardiac output (co) of (l min), and of the arteriovenous oxygen difference of . . the fourth patient's shock had mixed nature with svr of dynes.s.cm- and co of . (l min). all patients were discharged from the icu with a mean length of stay of days. conclusion: the dihydropyridine calcium channel blockers poisoning exposes to the shock risk due to several mechanisms. the clinician must be warned to look for signs of severity and understand its mechanisms by using the hemodynamic study in order to improve its management. goulmane mourad , alachaher djamel , djebli houria introduction: in daily practice, admission to the intensive care unit (icu) usually does not raise any major ethical problems. difficulties arise mainly in acute situations requiring intensive care that have not been anticipated and therefore, not adequately prepared and discussed. we hypothesized that non-admission of a patient to the icu must occur in the following circumstances-( ) with the patient's agreement, expressed either directly or through advance directives (ad), or as relayed by a surrogate or the family + ( ) according to a collegial decision-making process (if the patient is decisionally incapacitated) + and ( ) after seeking the opinion of an external consultant. the decision-making process must be documented in the patient's medical file. patients and methods: prospective, observational study in two hospitals (one large university hospital, one regional non-acamedic hospital) over a period of months. inclusion criteria were-patients aged ≥ years presenting with failure of at least organ that was directly life-threatening and requiring life-sustaining therapies. complete data collection was performed for each patient. results: a total of patients were included ( % from the emergency department and % from medical wards). the decision not to admit the patient to the icu was taken-( ) during night duty for patients ( %) + ( ) by a senior physician in %, and ( ) after clinical examination in ( %). the main reasons justifying the decision not to admit to the icu were-( ) metastatic cancer in patients ( %) + ( ) total loss of autonomy in ( %) + ( ) severe cognitive impairment in ( %) + ( ) premorbid state in ( %) + ( ) chronic organ failure for ( %) + and ( ) presence of ad (written or oral) specifying that the patient did not wish to be admitted to the icu in ( %). this study raises several points concerning the decision-making process for patients requiring intensive care. first, collegiality is observed in almost all situations of non-admission ( %). second, an outside consultant was contacted in around % of cases. third, % of patients had ad. fourth, the family or entourage were consulted in less than % of cases and finally, in around % of cases, the decision-making process was documented. conclusion: this study shows that in emergency situations, it is more difficult to take adequately structured decisions regarding icu admission than, for example, decisions regarding limitation or withdrawal of treatment in the icu. introduction: as known, tracheostomy is performed to improve quality of life (qol) in patients requiring prolonged mechanical ventilation. it is indicated to facilitate care of critically ill patients, in order to minimize risks of oro-tracheal intubation, and enhance recovery, allowing early discharge from icu with home ventilation. we aimed by this study to evaluate long-term survival and qol in tunisian patients discharged from the icu with tracheostomy, as well as related burden assumed by their relatives. patients and methods: patients who were admitted to the icu between and were eligible for inclusion in this retrospective cohort if they had a tracheostomy during their icu stay, and were discharged at home with a tracheostomy canula. for survivors, we used the short form health survey (sf ) to assess their qol at home. we estimated the degree of autonomy using the adl scale. to assess burden assumed by caregivers (family members most of the time) we used the short version of zarit burden interview. exclusion criteria were refusal of the interview or unavailability on the phone call. results: fourteen patients were discharged at home with a tracheostomy canula. only twelve responded to the phone call. four patients died month later. amoung the survivors, the removal of the tracheostomy canula was successful in patients after a mean duration of days. main findings are summarized in table . conclusion: tracheostomy shows good acceptance and acceptable qol. it allowed shorter length of stay in the icu and long-term survival after discharge from the icu, and should be encouraged for tunisian patients. in contrast, the qol of patients' relatives was more affected, with significant burden and work load. introduction: intensive care survivors present often some psychological disorders linked with experience memory loss or nightmares. the use of patient diaries has been developed and implemented by clinical staff to improve the quality of life after intensive care. patients received their diaries at icu discharge. this study was conducted in order to understand the potential benefits for patients the diary on prevalence anxiety, depression and post traumatic disorders during recovery. patients and methods: a structured interview study was administered to adult critical illness survivors who received ≥ h of mechanical ventilation in a medical and surgical intensive care unit. after months, this patients answered at two questionnaire-hospital anxiety and depression scale (had) and a screening instrument for ptsd (qspt). results: from the survivors at months, patients answered the questionnaires. we have two groups- patients had a diary and patients no diary. but these group are so low currently to compare introduction: in ards patients under ecmo common ventilator strategy aims at resting the lung by lowering tidal volume (vt) in the - ml kg predicted body weight range found in the literature analysis. we tested on the bench the not previously explored hypothesis that vt was not delivered in the % accuracy by most of icu ventilators in this low range. patients and methods: pneumatic test lung set at ml/cmh o compliance and cm h o/l/s resistance was attached to any of icu ventilators (v (drager), carescape r (ge healthcare), servo u (maquet), pb (covidien) and g (hamilton)) equipped with heated humidifier (fisher-paykel mr ) set off and adult ventilator circuit (rt evaqua fisher paykel). each icu ventilator was set in btps condition, at peep cm h o and fio . . airway pressure and airflow (hans-rudolph pneumotachograph) were measured (biopac m ) proximal to the lung model. for each ventilator a series of vt ranging from to ml was delivered for breaths each, at then at breaths/min respiratory rate (rr). the relationship of vt measured to vt set was assessed by linear regression over the icu ventilators for each circuit-rr combination. in each model, the change from the mean effect was assessed for each ventilator. for each model we obtained the mean effect of the ventilators then we compared the effect of each ventilator to the mean effect. results: for each combination of f and circuit, the mean slope was significantly lower than indicating that, on average, the set vt was under delivered (table) . there were differences in change in slope from the mean across the ventilators with interaction between ventilators and combinations. as an example, for the adult circuit f , carestation, pb and servo u performed better than g and v . across the combinations, v had consistent negative (greater underestimation than average) slopes and servo u consistent positive (lower underestimation than average) slopes whilst the slope sign in the three others changed direction. biomarkers. yet, hla-dr expression on alveolar monocytes was lower in ards than in controls, consistent with sepsis-induced immunosuppression at the alveolar level. functional differences observed between ards and controls suggested a tolerogenic profile of ards monocytes. introduction: despite their recommendation in the prevention of ventilator-associated pneumonia, oral care is not still clearly standardized. it generally includes a time for oropharyngeal and tracheal suctions which can induce a cough reflex in non-paralyzed patients leading to the mobilization of the endotracheal tube and a consecutively increased risk of tracheal microaspirations. during the oral care procedure, drainage of subglottic secretions at particular times before oro-tracheal suctions is expected to reduce microaspiration. the aim of this study is to assess whether this "optimized" oral care including subglottic drainage can reduce microaspirations. this is an open prospective study, including icu ventilated patients. two procedures have been compared in two randomized cross-over consecutive periods of one day each ( oral cares a day)-on day, they received routine oral care (oral care (o) then tracheal suction (t)) and on the other day they received optimized oral care (subglottic suction (sg ) then o then sg then t). the amylase enzymatic activity has been measured in o, t, sg and sg suctions as a surrogate for the oropharyngeal content. if present in t suctions, it defines microaspiration. since the amylase o content is not similar from a patient to another, the primary outcome was the median amylaset o ratio after routine versus optimized oral care. results: after informed consent, patients were included. were analyzed due to incomplete follow-up in patients. patients (sapsii ± ) were ventilated since . ± . days for a majority of respiratory indications. at day , and patients received routine oral or optimized oral car respectively without significant baseline difference. a trend in the reduction (− %) of amylase t o median ratio was observed after optimized versus routine oral care ( . % [ . - vs. . % [ . - ], p = . . conclusion: despite protection of trachea by the cuff of the endotracheal tube, amylase has been found in tracheal suctions (which represents the last step of oral care). in this pilot study with a limited sample of patients, a trend in the reduction of microaspirations was observed when subglottic suctions were interleaved between oral and tracheal suctions. an increased sample power could show more significant results, but we cannot eliminate that this weak effect could also be due to the inability of subglottic suctions to prevent microaspiration of the oral content. the study has been founded by teleflex. introduction: although necessary, mechanical ventilation can lead to ventilator-induced lung injury (vili) even when using protective ventilation strategies that combine low tidal volume (vt)( ml kg predicted body weight) and plateau pressure (pplat) <= cmh . lower positive pressures and tidal volumes could enhance lung protection + the hla-dr and pd-l expressions were higher on alveolar than on blood monocytes in both ards patients and controls (figure) . yet, hla-dr expression on alveolar monocytes was higher in controls compared to ards patients (p = . ). circulating monocytes had a higher phagocytic activity than alveolar monocytes (p < . ), but no significant difference was observed between ards patients and controls. an lps challenge increased the phagocytic activity of monocytes in controls (p = . ) but not in ards monocytes (p = . ). tnf-α intracellular synthesis was increased after lps exposure in circulating and alveolar monocytes of controls (p < . ) but only tended to do so in ards (p = . ). conclusion: differences in the phenotype of alveolar and circulating monocytes were observed in ards but also in controls, suggesting a physiological lung blood gradient in the expression of these results: until , ten patients were included and analyzed for the study. there was a significant difference between the volumes recruited at the three peep levels (p = . ). the recruitment evaluated was not correlated with pao . there is a significant decrease in cardiac index and pam caused by the increase in peep. conclusion: preliminary results from our study suggest that the estimated recruited lung volume estimated by crf inview ® technology appears to be poorly correlated with measured pao . the hemodynamic repercussions observed should also be considered in order to propose an optimal strategy for the optimal adjustment of peep. were compliant with the re-evaluation. ( %) patients received carbapenems according to the recommendations. a compliant prescription had no impact on hospital or icu length of stay and no impact on duration of mechanical ventilation but seemed associated with increase mortality (p = . ). discussion: the high rate of compliant prescriptions can be explained by the broad indications of carbapenems in the icu, especially in patients with septic shock. the increase mortality of patients with a compliant prescription is probably due to the severity of the infections. in order to achieve % compliance, we could suggested regularly updating the knowledge of carbapenems prescriptions, collaborating with bacteriology and infectiology teams, and establishing a computerized or paper prescription with feedback control. conclusion: the prescription of carbapenems appears most often in accordance with the recommendations in this icu. however, there is a need for improvement. introduction: bacterial infections are frequent triggers for diabetic ketoacidosis and a significant increase in morbimortality is observed in case of delayed antibiotic treatment. however the unnecessary administration of antimicrobial therapy can also lead to bacterial resistance. early sepsis markers are thus particularly useful for patients admitted in icu for diabetic ketoacidosis. patients and methods: we retrospectively studied cases of patients admitted in icu at avicenne french universitary hospital for ketoacidosis defined by ph < . and glycemia > . mmol l. clinical and biological data were analyzed at admission (d ) and on day (d ). results: between and , among patients admitted for diabetic ketoacidosis, were included. twelve out of were infected ( urosepsis, pneumonia, others). demographic data and comorbidities did not significantly differ between the infected and non infected group (ig and nig). antibiotics were administered to patients- ( %) in the infected group versus ( . %) in the non infected group. on d , there was no difference for-ph, temperature, leukocytes, neutrophils-to-lymphocytes count ratio and pct (table ) . on d , temperature, leukocytes, neutrophils-to-lymphocytes count ratio and pct were significantly higher in the ig. in the ig, the biological markers did not vary between d and d , whereas in the nig, leukocytes (p < . ), pnn (p < . ) and neutrophils-to-lymphocytes count ratio (p < . ) significantly decreased. surprisingly average pct levels seem to be particularly high in the nig on do as well as on d . conclusion: at admission, pct as well as other usual markers do not appear to be useful to differentiate infected from non infected patients admitted for ketoacidosis. however, on day , two different patterns can be drawn and help detecting non-infected patients and thus reduce exposure to antibiotics. these results should be confirmed by a prospective study, including a larger number of patients. ventilator-associated events (vae), reflecting worsening oxygenation, are defined as a persistent and significant increase in fio or peep level after a period of stability on the ventilator. vae definition includes ventilator-associated conditions (vac), infection-related ventilatorassociated complications (ivac) and probable ventilator-associated pneumonia (pvap). the relevance of vae for ventilator-associated pneumonia (vap) is low. however, the correlation between the three vac, ivac, and pvap, and the onset of ventilator-associated low respiratory tract infection (valrti), including ventilator-associated tracheobronchitis (vat) and pneumonia (vap), has never been studied yet. we on clinical examination. gravity scores-apache ii and saps ii. for lumbar puncture data, there is the proteinuria, glycorrhaphy resuscitation measures-drug intake and intubationin multivariate analysis, the factors of pejorative evolution-the male sex presence of meningeal syndrome. high proteinorachia. taking vasoactive drugs. the saps ii score. conclusion: according to this work, many factors influence the prognosis of acute meningitis in our population such as severity general scores, hemodynamic state and initial lumbar puncture data. we will need more investigations and prospective multicentric study to have more discrimination parameters. introduction: the emergence of atb-resistant bacteria has become an important public health problem, particularly in resuscitation environments, surveillance and monitoring of atb consumption is essential to combat this threat ecologically and economically. the aim of this work was to evaluate the consumption of atb in surgical resuscitation, to establish the cost, and to list the risk factors for bacterial resistance. patients and methods: it is a retrospective analytical study spread over year, studying patients who have received antibiotic therapy, the data on the consumption of atb were collected from the patient's medical records, the delivered doses were converted into ddd, according to the who standards and the end result is expressed in ddd days of hospitalization. the statistical analysis was carried out by the spss software. results: in our study, the mean age was . ± . , with male predominance + sex ratio . , traumatic pathology is the most common reason for admission, pneumopathy was the most frequent infection. overall atb consumption was . ddd dh, dominated by the class of betalactamins (cephalosporins . ddd dh, carbapenemes . ddd dh), the direct cost of atbs rises to . million dirhams, these are accounting for a large part of the pharmaceutical budget of the ibn rochd university hospital. bacteria found in order of frequency were acinetobacter baummanii, beta-lactamaseproducing enterobacteria, s. aureus and p. aeruginosa. acinetobacter baumannii showed the highest resistance rate. several risk factors for bacterial resistance were studied, notably the correlation between the use of atb and the emergence of resistant strains, only piperacillintazobactam was associated with the emergence of resistant strains of eblse, as well as other factors that were retained as significantly related to bacterial resistance by multivariate analysis-duration of hospitalization and perfusion of albumin. discussion: despite the limited number of studies done on atb consumption, it seemed that our results were similar to other national and foreign studies, the consumption of atbs is increased in hospital giving rise to the appearance of many multi-resistant bacteria. conclusion: in conclusion, resistance to antibiotics is a serious threat to public health both nationally and globally. it is therefore crucial to implement measures to counter this phenomenon + this is only possible through the proper use of atbs and gaits to prevent nosocomial infections. introduction: ventilaor-associated pneumonia (vap), the leading cause of infection in resuscitation, is also the main respiratory complication in cranial trauma. the aim of this study is to determine the specific risk factors for the occurrence of vap in this type of patient in an intensive care unit. patients and methods: we performed a retrospective study in our intensive care unit for an -month period (january , june ). all patients admitted for cranial trauma were included in the study and ventilated more than h in intensive care. vap is defined as late as of the th day of occurrence. the quantitative and qualitative variables studied were recorded at admission and during hospitalization. a univariate and multivariate analysis using the fischer and mann-whitney tests was performed. p is said to be significant if it is < . . results: our study included traumatic brain injury in older adults, of whom ( %) had one or more episodes of vap during their resuscitation. late vap accounted for almost of the cases ( patients). four independent variables were significantly related to the occurrence of vap-advanced age (p = . ), glasgow score (gcs) at admission < (p = . ), diabetes (p = , ), and the use of proton pump inhibitors for the prevention of stress ulcers (p = . ). the duration of intubation ( ± vs. ± days) and on intensive care ( ± vs. ± days) are significantly longer in the case of vap. mortality was significantly higher in vap- versus % (p = . ). the majority of early vap were due to both strepococcus ppneumoniae and haemophilus influenzae. the ecology of late vap was dominated by klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumanii. conclusion: of the four independent risk factors found in our study, glycemic balance and rapid airway safety by orotracheal intubation in the case of initial gcs < represent the relevant prevention axes of vap in traumatic brain injury in older adults. unfortunately, it is accompanied by a significant increase in bacterial resistance to antibiotics, leading to an increase in morbidity and mortality in intensive care units. patients and methods: this is a retrospective study carried out in our intensive care unit, covering all patients hospitalized between january and june and having contracted a nosocomial urinary infection. patients whose hospital stay was less than h and those fig. agreement between vae and lrti diagnostic with a nosocomial urinary tract infection acquired in another service were excluded. results: the study of resistance of the germs responsible for nosocomial urinary tract infection showed that-escherichia-coli was resistant to third generation cephalosporins in % of cases, at imipenem in % of cases, and without resistance to ertapenem and amikacin. pseudomonas was resistant to ceftazidime in % of cases, to imipenem in % of cases and to amikacin in % of cases. acinetobacter baumannii was resistant to imipenem in % of cases and to amikacin in % of cases. enterococcus faecalis had no resistance to vancomycin and ampicillin. staphylococcus aureus was resistant to methicillin in % of cases and without any resistance to vancomycin. mortality directly associated with nosocomial urinary tract infection was %. the comparison with previous studies has shown a significant increase in the bacterial resistance responsible for nosocomial urinary tract infection, which is of interest in monitoring the ecology of intensive care units and the resistance profile as well as the improvement of the management of antibiotics. introduction: nosocomial enterococcus infections are a constant concern in intensive care units due to their increasing frequency and the emergence of resistant strains to vancomycin. the aim of our study was to compare outcome findings of patients with nosocomial enterococcus infections according to their sensibility to vancomycin, and then to investigate predictive factors of mortality. patients and methods: it was a retrospective descriptive study, including all hospitalized patients in intensive care, between january st, and april st, , with nosocomial enterococcus infections. we recorded demographic and clinical findings, severity scores igs ii, apache ii, initial sofa and sofa at the time of infection, microbiological, therapeutic and outcome data. patients infected with vancomycin-susceptible enterococcus (vse) were compared to those having vancomycin-resistant enterococcus (vre) + then we searched for independent risk factors for vre. finally, a multivariate logistic regression was conducted to investigate independent predictive mortality factors. results: during the study period ( years and months), patients presented a nosocomial enterococcus infection with a median age of years [ - ] and a sex-ratio of . . at admission, patients ( . %) had respiratory distress. the median scores of igs ii, apache ii, initial sofa and sofa at the time of infection were respectively + + and . the infection sites were-urinary infection (n = , . %), bacteremia (n = , . %) and central line associated infection (n = , . %). patients had a vre nosocomial infections and vse. a septic shock complicated enterococcus infection in cases including cases of vre and cases of vse (p = . ). vre nosocomial infections were significantly related to arterial (p = . ) and venous (p = . ) femoral catheterization, to a duration of venous femoral catheterization > days (p = . ) and to e. faecium species (p < - ). no independent risk factor of vre was found. the median duration of hospitalization was days and the overall mortality rate was . %. multivariate analysis identified independent predictive factors of attributable mortality-patients in coma (or . + ic % = . - . + p = . ) and the occurrence of septic shock (or . + ic % = . - . + p = . ). conclusion: attributable mortality to nosocomial enterococcus infections was high and independent of the susceptibility of the strain to vancomycin. mortality was independently associated to septic schock occurrence and neurologic dysfonction. introduction: ventilator-associated pneumonia (vap) is defined by a lung infection contracted h after the putting under mechanically assisted breathing. risk factors predisposing to the development of vap among mechanically ventilated patients are many. some are related to the patient as age, history of copd, presence of an altered state of consciousness + others are related to care providing. patients and methods: a prospective nested case control study was conducted from marsh through april . all icu patients mechanically ventilated for more than h with endotracheal intubation or tracheostomy were included. cases of community-acquired pneumonia, non-mechanical ventilated hospital-acquired pneumonia, end-life patients and those aged less than years were excluded. the included patients with vap and those without vap were matched based on the age, the severity score and the comorbidities. for all patients included, preventive measures as assessed by the recent guidelines for preventing vap were applied after an education period of all medical and paramedical staff of the icu. the collected data are-age, comorbidities, admission severity scores, time to onset of vap, prior antibiotic therapy at the onset of vap, need for tracheostomy, duration of mechanical ventilation, length of stay in icu and become. results: during the study period, patients were mechanically ventilated. vap was observed in % of cases. vap was observed in cases with an incidence of % and incidence density of per patient-days of mechanical ventilation (mv). in univariate analysis, significant difference was found between the group with vap and the group without vap regarding admission for poly trauma, acute respiratory failure, the concept of prior antibiotic therapy, the need tracheostomy, the number of days alive without antibiotics and without mv, the duration of mechanical ventilation, length of stay and mortality. multivariate analysis showed that prior antibiotic therapy and the use of tracheotomy were independent factors for developing vap. prolonged duration of mechanical ventilation was an independent predictor of mortality in multivariate analysis with or . + % [ . to . ], p = . . the occurrence of vap was not an independent predictor to mortality. conclusion: the incidence of vap found in our study is similar to that found in the literature. an active strategy of rationalizing the prescription of antibiotics in intensive care units and a well-defined protocol of weaning from mechanical ventilation may reduce the incidence of vap and over-all morbidity and mortality. introduction: hyperoxemia is common in critically ill patients. hyperoxic acute lung injury (hali), reduced bacterial clearance, atelectasis and higher mortality rates were reported in mechanically ventilated patients with hyperoxemia. the aim of our study was to determine the relationship between hyperoxemia and mortality in patients with ventilator-associated pneumonia (vap). this retrospective observational single center study was performed in a -bed mixed intensive care unit (icu) during a -year period, from january to january . all patients with vap were included. vap was defined using clinical, radiological and quantitative microbiological criteria. hyperoxemia was defined as peripheral capillary oxygen saturation-spo ≥ %. spo was hourly collected in all study patients during the whole period of mechanical ventilation. the daily percentage of time spent with hyperoxemia was calculated as the number of hours with hyperoxemia divided by . results: among the patients receiving invasive mechanical ventilation (mv) > h during the study period, the incidence rate of vap was . vap per ventilator-days. patients developed vap and were all included in this study. ( %) vap patients died in the icu. the mean daily time spent with hyperoxemia was %. no significant difference was found in mean percentage of time spent with hyperoxemia between survivors and nonsurvivors at icu admission, before, after or at the vap diagnosis. age, and sequential organ dysfunction assessment (sofa) at the day of vap occurrence were independently associated with icu mortality (or . [ . - . ] per year, p = . + . [ . - . ] per point, p = . + respectively). no significant impact was found of time spent with hyperoxemia before vap occurrence, on mv free days, or icu length of stay (fig. ). discussion: several potential explanations could be provided for the absence of negative impact on mortality of hyperoxemia. first, the definition used for hyperoxemia could be debated, as no consensus exists. however, the definition used in our study was rather stringent and the mean daily time spent with hyperoxemia was in line with that reported by studies. second, the impact of hyperoxemia on mortality could have been confounded by a large number of patients included with pulmonary lesions at admission. third, the number of included patients was small. conclusion: our study found no significant impact of hyperoxemia at icu admission, or during icu stay, on icu mortality in vap patient. results: patients collected during this period. distal protected specimens were performed in patients suspected of vap. the diagnosis of this infection was made. in of them with other diagnostic criteria ( %) which represents an incidence density of . per , days. % of pavm are due to gram negative bacilli. the first germ involved in our series and pseudomonas ( %) followed by klebsielles ( %) followed by acintobacter baumanii ( %) enterobacteries representing the rest. % lung infection with gram-positive cocci (principally sensitive methicillin) pseudomonas was imipenem resistant in . %, baumanii was imipenem resistant in %. the resistance profile of the recovered germs (baumanii and pseudomonas) encourages the utmost rigor in the management of these patients, prevention is better attitude to adopt. introduction: the ventilator associated pneumonia (vap) appear in the second rank of the infections acquired in hospital after the urinary infections. the diagnosis is based on a beam of clinical, biological, radiological and bacteriological arguments. this work consisted of an epidemiologic analysis of the vap and aimed at evaluating of it the frequency, the risk factors, the antibioresistance of the isolated bacteria and the mortality factors. patients and methods: this retrospective study related to patients hospitalized in icu during a period of years from january to december . the study included all patients over years and ventilated more than h and developing vap. results: bgn predominant and represent . % of identified germs, the acinetobacter baumanni leads with . %, followed by klebsiella pneumonia ( . %), followed by pseudomonas aeruginosa ( . %), followed by e. coli ( . %), followed by enterobacter cloacae ( . %) and citrobacter frendi ( . %). the cocci gram positive (cgp) constitue . % of isolated germs of witch . % staphylococcus aureus, . % of non aureus staphylococci, . % streptococcus sp. the polymicrobism was found in % cases. the isolated germs were multiresistants. in this study, we find a very high mortality and a major additional morbidity of the np by prolongation of hospitalization, of mechanical ventilation and a major additional cost.conclusion: it appears in the light of this work that a strategy of prevention based on the strict application of hygiene measurements, the maintenance of the material of ventilation and the respect of care procedures prove to be urgent in our context. introduction: burns induce modification of distribution volume, increased clearance of drugs and decrease of protein binding. amikacin pharmacokinetics (pk) was altered with subthera-peutic serum concentrations. the aim of our study was to assess the pk of amikacin in burns after a loading dose given once a day according to this equation-dose(mg kg) = *pi( * , *dp ) + ( * , * dp ). threshold for therapeutic efficacy was a ratio of ≥ between the concentration achieved h after beginning the infusion (c peak) and the minimal inhibitory concentration (mic) of the isolated pathogen. patients and methods: this study was conducted in burn center in tunis. patients with documented and or suspected infections were included. were excluded pregnant women and patients with renal failure. enrolled patients received amikacin at a loading dose in h infusion. blood samples for pk analysis were assessed during days (total duration of amikacin)-immediately after the end of the first infusion (t ) and min after (t ) at day . for the nd, rd, th and th day, blood samples were taken before the infusion (t ), at the end (t ) and min after the end of it (t ). results: burned patients were included. the mean age was ± years with a body weight of ± kg. the mean dose of amikacin was mg kg day [ - mg kg day]. a peak between and μg/ml was reached in % of cases, corresponding to times the mic, break-points for enterobactericeae and pseudomonas aeuroginosa. total volume of distribution was . l kg ( . - . ) l kg, half-life time (t ) was . h [ . - h] and the amikacin clearance was . l h. a correlation was found between cpeak at day and cpeak at day (r = . ). conclusion: our study shows that an early achievement of an optimal cpeak mic ratio of amikacin was reached in half of cases with a correlation between cpeak in the beginning and at the end of treatment. so, initial cpeak was useful tu adjuste amk therapy in burns and predicts treatment efficacy. *pi-ideal weight + dp -admission weight-ideal weight + dp -actuel weight-admission weight. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -o hr mox authors: nan title: proceedings of réanimation , the french intensive care society international congress date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: o hr mox nan rationale: expiratory muscles has recently been stated as the «neglected component» in mechanically ventilated patient. several authors stated these muscles importance in cough capacity, contractile efficiency of the diaphragm or reduction of hyperinflation. however, few studies reported potential factors leading to expiratory muscle weakness and its importance on weaning success or survival after mechanical ventilation. patients and methods: this study is a secondary analysis of our previously described cohort of patients ventilated for at least h assessed for respiratory muscles function. maximal expiratory pressure (mep) measurement was carried out during spontaneous breathing trial using a manometer with an unidirectional valve. mep diagnostic accuracy to predict icu-aw (icu acquired weakness), weaning success and sursvival within days were assessed using expiratory muscle strength as absolute values (cmh o), as %predicted values and as %lower limit of normal. results: due to the paucity of data reporting threshold value for expiratory muscle weakness, we considered our median value ( cmh o (iqr )) as the threshold value for expiratory muscle weakness group (mep ≤ cmh o) and normal expiratory muscle group (mep > cmh o). patients with low mep received more catecholamines (p = . ) and a higher duration of mechanical ventilation (p = . ). inversely, higher body mass index was associated with higher mep. patients with low mep presented more icu-aw compared to normal mep patients ( % vs. %; p = . ). no other outcomes were different between groups. mep was statistically able to predict icu-aw but area under (auc) receiving operating curves showed weak predictive ability (auc: . ( % ic . - . ; p < . ) for a threshold value ≤ cmh o. expiratory muscle weakness was unable to predict critical outcomes when adjusting mep to the %predicted or lower limit of normal. discussion: possible explanation is that contrary to inspiratory muscle weakness, cough inefficacy after weaning from mechanical ventilation could be managed with cough supplementation techniques (i.e. mechanical in-exsufflation). conclusion: in our cohort, mep was not associated with mechanical ventilation weaning or death. despite our results, different clinical techniques for quantifying expiratory muscle weakness may provide more beneficial results. compliance with ethics regulations: yes rationale: venoarterial extracorporeal membrane oxygenation (va-ecmo) is used to support tissue perfusion during extracorporeal cardiopulmonary resuscitation (e-cpr). shock, resuscitation and the extracorporeal circuit may trigger a capillary leakage and a vasoplegic shock. currently, in these situations, high doses of norepinephrine (ne) are required. because high ne doses may have significant cardiovascular side effects, alternative options to support arterial blood pressure are needed. in recent years, several approaches to decrease the administration of high ne doses have been tested, one of them is the administration of vasopressin (avp). randomized trials have shown that avp infusion increases arterial pressure and systemic vascular resistance, decreases catecholamine requirements in patients with or at high risk of vasoplegic syndrome and attenuates vascular dysfunction. currently, no data are available for the study of the effects of avp in shock state in post refractory cardiac arrest. patients and methods: pigs were randomized into two groups, in order to receive avp or ne. a refractory cardiac arrest of ischemic origin was surgically created and va-ecmo was started after a min period of cardio-pulmonary resuscitation. then, resuscitation lasted h in each randomization group. the evolution of the consequences of the shock was evaluated by lactatemia and microcirculation (sdf and nirs) at baseline hour, h (when ecmo starts), h and h . renal and hepatic functions were assessed. results: experimental conditions were met for animals (avp, n = ; ne, n = ). the groups were comparable on the shock impact and its severity. no significant differences were found between populations for ecmo flow and map. there was a significant difference on fluid volume resuscitation amount ( [ . - . ] ml in the ne group versus ml in the avp group, p < . ) (fig. ). no significant difference between the ne and avp groups for lactate clearance between h and h ( . [− . to . ]% vs . [ . - . ]%, p = . ). we did not find any significant for sublingual microcirculation indices and nirs values. renal and liver function evolution were similar in the two groups during the protocol. conclusion: avp administration in refractory cardiac arrest resuscitated by va-ecmo when compared to ne is associated with less fluid volume for similar global and regional hemodynamic effects. compliance with ethics regulations: yes. patients and methods: a single-center prospective study. patients younger than months with severe bronchiolitis and supported by niv or hfnc were included. niv/hfnc was discontinued according to the local practices and no protocol existed. exceptt the principal investigator, the attending team was blinded to the study. weaning failure was defined as the need to reinstate niv/hfnc in the h after discontinuation. ethical approval was not necessary for this study in accordance with the french data protection autority methodology reference number mr- . results: a total of patients (median age days, ( %) males) were included. respectively, ( %) and patients ( %) were supported by niv and hfnc at admission (fig. ) . regarding the mode of niv, a bilevel mode was used in patients ( %) (fig. ). in patients supported by hfnc, the ventilatory support was discontinued progressively by decreasing air flow in patients ( %) while it was stopped abruptly in ( %). in patients supported by niv, the respiratory support was stopped abruptly in ( %) of them while hfnc was used as a weaning method for ( %) patients. a total of ( %) patients experienced a weaning failure. patients supported by niv/ hfnc who experienced a prompt weaning had a lower pediatric intensive care unit (picu) length of stay as compared to patients in whom hfnc was used as a weaning method ( ± h versus ± h, p = . ). however, the hospital length of stay was similar according to the weaning method ( ± days versus ± days for prompt and progressive methods respectively, p = . ). the duration of the weaning process did not differ according to the bed-availability in picu. in patients with severe bronchiolitis, a prompt weaning from niv/hfnc was associated with a lower length of stay in picu. however, the hospital length of stay was similar according to the weaning method. we suggest that a prompt weaning should be preferred in order to reduce the risk of picu related complications. compliance with ethics regulations: yes. information and incitation to open a twitter account and to follow critical care journal feeds) or group (control group). ict were interrogated on their recent medical literature knowledge at and month on trials published in pre-selected journals. results: during the study period, on the french ict contacted, agree to participate: were already on twitter, were randomized to twitter incitation and to control group. at month, there were who answered electronic questionnaire. self-declaration of article knowledge was not different between groups (p = . ). knowledge of primary outcome of each trial was not significantly better in groups (p = . ). in per-protocol analysis of ict on twitter or not, knowledge of article and primary outcome were also not significantly different (respectively p = . and p = . ). short incitation to open a twitter account and follow major medical journals with specific focus on cardiac arrest did not improve knowledge of medical literature by intensive care trainees at month. further trials are needed to better imply intensive care trainees in scientific medical literature. compliance with ethics regulations: yes. - . ] ; p = . ) as independently associated with in-hospital mortality ( fig. ). discussion: triple therapy is the recommended first-line treatment of caps. however, herein, it was not significantly associated with better survival in critically ill, thrombotic aps patients. for the subgroup of "definite/probable caps" patients, double and triple regimens were associated with survival. but the bivariable analyses including the day- saps ii showed that survival was linked to in-icu anticoagulation and corticosteroids-not ivig or plasmapheresis. our findings indicate that corticosteroids should probably be added to in-icu anticoagulation to treat "definite/probable caps". frequent fever and elevated c-reactive protein in all thrombotic aps patients suggest a marked inflammatory state that could explain corticosteroid efficacy. neither plasmapheresis nor ivig impacted the prognosis of "definite/ probable caps", but that finding could be explained by a lack of power compared to caps registry data. conclusion: in-icu anticoagulation was the only aps-specific treatment independently associated with survival for all patients. doublebut not triple-therapy was independently associated with better survival of "definite/probable caps" patients. in these patients, double therapy should be used as first-line therapy while the role of triple therapy requires further evaluation. compliance with ethics regulations: yes. motor deficiency ( %) ( %) ( %) . cognitive impairment ( %) ( %) ( %) . intra-individual relationships between Δpdi and tfdi for mechanically ventilated (mv) patients (a) and healthy subjects (c). relationships between Δpdi and tfdi when breathing cycles were averaged for all participants during each condition for mv patients (b) and healthy subjects (d). − %: initial settings minus % inspiratory help, + %: initial settings plus % more inspiratory help, pep : zero positive end-expiratory pressure, sbt: spontaneous breathing trial. healthy subjects performed spontaneousbreathing (sb) and ventilation against inspiratory threshold at , , , and % of maximal inspiratorypressure (mip) groups. airway closure occurrence increased with bmi ( %, % and %, p = . ). when present, airway opening pressure was . cmh o ( . - . ) and similar between the groups. with increasing bmi, total peep increased from . to . cmh o between groups (p = . ). all values of esophageal pressure increased with bmi. endexpiratory esophageal pressure was strongly correlated with bmi (rho = . , p < . ), as illustrated in fig. . consequently end-expiratory transpulmonary pressure decreased from − . to − . cm h o with increasing bmi (p = . ). the ratio of eelv to predicted functional residual capacity was negatively correlated with end-expiratory pressure (rho = − . , p = . ), but not with bmi. driving pressure and elastance of the respiratory system, chest wall and lung were similar across all ranges of bmi. likewise, eelv was similar between groups. conclusion: in ards, increasing bmi is associated with increased occurrence of airway closure and increased values of esophageal pressure. conversely, chest wall elastance is not influenced by bmi, as well as lung elastance. including bmi in interpreting respiratory mechanics in ards patients can provide additional information for the clinical management. compliance with ethics regulations: yes. rationale: low tidal volume is the cornerstone of protective ventilation inthe initial phase of ards ( ) . whether such low tidal volume can still be achieved when the patient is allowed to breathe spontaneously under pressure support ventilation (psv) is unknown. in moderate-tosevere ards patients receiving neuromuscular blockade, we assessed the tidal volume and its potential association with the outcome during the "transition period" following neuromuscular blockade. patients and methods: retrospective observational study in two university intensive care units. patients fulfilling moderate-to-severe ards criteria less than h after intubation and receiving neuromuscular blockers were included upon entry in the "transition period". we defined the "transition period" as the h following neuromuscular blockers cessation. ventilatory and hemodynamic parameters were recorded every h during the "transition period". primary outcome was the association between mean tidal volume under pressure support ventilation (psv) during the "transition period" and the -day mortality after adjustment for confounding factors. data are reported as median [ st- rd quartile] or number (percentage). results: one hundred nine patients were included, with a pao /fio ratio of mmhg at intubation and mmhg at inclusion and a sofa score at [ . - ] . patients had been ventilated days [ - . ] before inclusion. during the "transition period", patients ( . %) were switched to psv. the median duration of psv was h . the mean tidal volume under psv was significantly lower in survivors than in non survivors at day ( . ml/kg [ . - . ] vs. . ml/kg [ . - . ] respectively, p = . ). by multivariate analysis (cox proportional hazards regression model), mean tidal volume during psv remained independently associated with the -day mortality after adjusting for sofa score and immunosuppression. patients with a mean tidal volume above ml/kg under psv during the "transition period" had a lower cumulative probability of survival at day as compared with others (log rank test, p = . ) (fig. ) . conclusion: in patients with moderate-to-severe ards, a higher tidal volume under psv within the h following neuromuscular blockers cessation is independently associated with the -day mortality.compliance with ethics regulations: yes. kaplan-meier estimate of the cumulative probability of survival according to the mean tidal volume (vt)-lower of higher than ml/ kg-under pressure support ventilation (psv) during the "transition period" transfusion is associated with adverse events, and equipoise remains on the optimal transfusion strategy in oncologic patients in surgical setting. patients and methods: this is a retrospective, single center study. all adults admitted to the intensive care unit (icu) after oncologic surgery from january to december were eligible. the following types of surgery for cancer or metastasis resection with a high risk of bleeding were eligible: thoracic, abdominal, neurosurgery, gynecologic, urologic, otorhinolaryngology or spinal surgery. the primary outcome was a composite outcome including post-operative complications (respiratory, cardiac, renal, thromboembolic, infectious and/or hemorrhagic) and/or hospital mortality. results: of the patients included, patients ( . %) had anemia (based on the who definition: hemoglobin level - . g/dl for female; hemoglobin level - . g/dl for male), patients ( %) had moderate anemia (hemoglobin level: - . g/dl) and patients ( . %) severe anemia (hemoglobin level < g/dl). fifty-six patients ( . %) received at least one rbc transfusion during their hospital stay. patients exposed to moderate and severe anemia required more often renal replacement therapy (rrt) for acute kidney injury (aki) ( . % vs. . %; p = . ), had more surgery-related infections ( . % vs. . %; p = . ). patients who received rbc had more often aki with rrt ( . % vs. . %; p < . ), thromboembolic events ( . % vs. . %; p = . ), sepsis ( . % vs. . %; p = . ), pneumonia ( . % vs. . %; p = . ), surgical site infections ( . % vs. . ; p < . ) and second surgery for infection ( % vs. . %; p = . ). the multivariate analysis found an association between moderate and severe anemia (moderate anemia: or . [ . - . ] ; severe anemia: or . [ . - . ]; p = . ) and severe post-operative complications (fig. a) . there was also an association between rbc transfusion and severe post-operative complications ]; p < . ) (fig. b) . conclusion: anemia was frequent in oncologic surgical patients. anemia, including moderate anemia, was independently associated to patient outcomes; however, rbc transfusion also negatively impacts on patients' prognosis. our study highlights the need for further research to identify the optimal hemoglobin threshold for rbc transfusion in surgical oncologic patients. compliance with ethics regulations: yes. rationale: right ventricular (rv) failure is a common complication in moderate to severe acute respiratory distress syndrome (ards). rv failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. veno-venous extracorporeal co removal (ecco r) might allow ultraprotective mechanical ventilation strategy with a low tidal volume (vt) and plateau pressure (pplat). this study investigated if ecco r therapy could have beneficial effects on rv function. patients and methods: this prospective monocentric pilot study was conducted in a french icu from january to march . patients with moderate to severe ards with pao /fio ratio between to mmhg were enrolled. ventilation parameters, arterial blood gases, echocardiographic parameters performed by transthoracic echocardiography (tte), low-flow ecco r system operational characteristics, outcomes and adverse events were collected during the protocol. primary end point was evolution of rv echocardiographic parameters with ultraprotective ventilation strategy at ml/kg pbw during the -h following the start of ecco r. results: eighteen patients were included. efficacy of ecco r allowed an ultraprotective strategy in all patients. we observed a significant improvement of rv systolic function parameters assessed by tte (fig. ). tricuspid annular plane systolic excursion (tapse) increased significantly under ultraprotective ventilation compared to baseline (from . to . mm; p < . ). systolic excursion velocity (s') also increased after -day protocol (from . m/s to . m/s; p < . ). a significant improvement of aortic velocity time integral (vtiao) under ultraprotective ventilation settings was observed. there were no significant differences in the values of systolic pulmonary arterial pressure (spap). when patients were separated in two groups according to baseline paco level above or under mmhg, we showed the deleterious effect of hypercapnia on rv function, and observed in both groups a beneficial impact of an ultraprotective ventilation strategy on tapse. no severe adverse events directly related to ecco r were observed in our small cohort. conclusion: the low-flow ecco r allows ultraprotective ventilation strategy and improve rv function in moderate to severe ards patients. similarly to prone positioning, ecco r could become a strategy that enables to reconcile lung protective approach with rv protective approach in ards patients. large-scale clinical studies, including patients with severe rv dysfunction, will be required to confirm these results and to assess the overall benefits, in particular the best timing of beginning ecco r in ards patients. compliance with ethics regulations: yes. rationale: bronchoalveolar lavage (bal) is usually deemed to allow the diagnosis of a large array of pulmonary diseases and is usually considered as well tolerated in intensive care unit (icu) patients. however, recent data suggest that the diagnostic yield of bal could be rather low ( ) , and may question its innocuity ( ) . the present study aimed at assessing the benefit-to-risk balance of bal in icu patients. patients and methods: the study was approved by the appropriate ethics committee and registered with clinicaltrials.gov (nct ). in icus, from april to october , we prospectively collected adverse events (ae) during or within h after bal and assessed the bal input for decision-making in consecutive adult patients. aes were categorized in grades of increasing severity. the occurrence of a clinical ae at least of grade , i.e. sufficiently severe to need therapeutic action (s), including modification (s) in respiratory support, defined poor bal tolerance. the bal input for decision-making was declared satisfactory if it allowed to interrupt or initiate one or several treatments. results: we included bal in patients (age yrs ; female gender: [ . %]; simplified acute physiology score ii: ; immunosuppression [ . %], chronic pulmonary disease [ / ( . %)]). bal was performed either in non-intubated patients receiving standard o therapy (n = [ . %]), or noninvasive ventilation (n = [ . %]), or high-flow nasal cannula o therapy ( [ . %]), or in patients under invasive mechanical ventilation (n = [ . %]). a total of aes were observed in ( . %) patients. sixty-seven ( . %) patients reached the grade of ae or higher. the main predictor of poor bal tolerance identified by logistic regression was the association of a bal performed by a non-experienced physician (non-pulmonologist, or intensivist with less than years in the specialty or less than bal performed) in non-intubated patients (or: . [ % confidence interval . - . ] ; p < . ). ordinal regression also showed that when bal was performed by a non-experienced physician in a non-intubated patient, this was associated with an increased risk of ae of any grade (or: . [ . - . ]). a satisfactory bal input for decision-making was observed in ( . %) cases and was not predictable using logistic regression. conclusion: adverse events related to bal in icu patients are frequent, and sometimes serious. our findings call for an extreme caution when envisaging a bal in icu patients and for a mandatory accompaniment of the less experienced physicians. compliance with ethics regulations: yes. meningitis is a rare complication of critically ill patients with severe pneumococcal community-acquired pneumonia paul jaubert, julien charpentier, jean-daniel chiche, frédéric pene, alain cariou, guillaume savary, marine paul, jean-paul mira, mathieu jozwiak cochin, paris, france; mignot, versailles, france correspondence: paul jaubert (paul.jaubert@gmail.com) ann. intensive care , (suppl ): rationale: severe pneumococcal community-acquired pneumonia (pcap) is a frequent infection requiring intensive care unit (icu) admission. pneumococcal meningitis associated with pcap has been reported and could worsen the prognosis of patients. however, this complication is difficult to predict and lumbar puncture is not systematically performed, regardless the severity of pcap. thus, we investigated the characteristics of patients with pcap associated with pneumococcal meningitis. patients and methods: we retrospectively included all patients admitted for pcap in our icu between (inception of our electronic medical sheet) and the end of . community-acquired pneumonia was defined according to the criteria of the american thoracic society. we excluded all patients admitted in icu with initial suspicion of meningitis. variables regarding epidemiology, clinical and microbiological characteristics, management and prognosis of these patients were collected and analyzed. results: among the patients admitted for pcap ( ± years old, saps ii ± , % of men), % of the patients required mechanical ventilation and % vasopressors infusion. the icu mortality was %. s. pneumoniae was documented by a positive antigen test in % of the patient and/or by a positive sputum smear, tracheal aspirate or distal protected airway specimen in % of the patients, and/or by pleural aspirate in % of the patients and/or by positive blood culture in % (n = ) of the patients. a lumbar puncture was performed in % (n = ) of the patients with bacteriemia and in % (n = ) of the patients without bacteriemia, with a median delay of h [interquartile range: after the onset of antibiotherapy. alllumbar punctures (n = ) were performed for neurological signs: % of coma, % of confusion and % of seizures. when a lumbar puncture was performed, meningitis was diagnosed in % (n = ) of the patients with bacteriemia and in % (n = ) of the patients without bacteriemia (p < . ). the icu mortality ( % vs. %, respectively), age ( ± vs. ± years old, respectively), saps ii ( ± vs. ± , respectively) or icu length of stay ( ± vs. ± days, respectively) were not different between patients with and without meningitis (each p = ns). conclusion: meningitis is a rare complication of pcap and is more frequent in patients with bacteriemia. suprisingly, meningitis is not associated with higher icu mortality. further analyses are ongoing to identify independent risk factors of meningitis in patients with pcap. compliance with ethics regulations: yes. rationale: shock is the clinical expression of a circulatory failure that results in inadequate cellular oxygen utilization. whereas the host response to septic shock has been extensively described, knowledge of the pathogenesis of non-septic shocks remains limited. we aimed to characterize the systemic host response in shock related to non-septic conditions (nssh) as compared with septic shock (ssh). patients and methods: we performed a prospective study in two intensive care units (icus) in patients admitted for ssh (n = ) or nssh (n = ). immune responses were determined upon icu admission by measuring plasma biomarkers reflecting host response pathways implicated in the pathogenesis of critical illness (in ssh and nssh patients), and by applying genome-wide blood mrna expression profiling (in ssh and nssh patients). results: compared with nssh, patients with ssh had more chronic comorbidities, greater disease severity (apache iv score vs. , p < . ) and worse outcomes resulting in higher mortality rates up to one year after icu admission ( . % vs. . %, p < . ). plasma biomarker analysis revealed severely disturbed host responses in both ssh and nssh patients. however, ssh patients displayed more prominent inflammatory responses, endothelial cell activation, loss of vascular integrity and a more pro-coagulant state relative to nssh patients. blood leukocyte genomic responses were more than % common between ssh and nssh patients relative to health (fig. a) , comprising overexpression of innate pro-and anti-inflammatory pathways, and underexpression of lymphocyte and antigen-presentation gene sets. direct comparison of ssh to nssh patients matched for severity (fig. b) showed overexpression of genes involved in mitochondrial dysfunction and specific metabolic pathways, and underexpression of lymphocyte, nf-κb and cytokine pathways. conclusion: patients with ssh and nssh present with largely similar host response aberrations at icu admission; however, patients with septic shock show more dysregulated inflammatory and vascular host responses, as well as specific leukocyte transcriptome alterations consistent with greatermetabolic reprogrammingand more severe immune suppression. compliance with ethics regulations: yes. rationale: aki is associated with short and long term mortality and morbidity. although recovery has been demonstrated to be associated with outcome of critically ill patients, interpretation of available data is limited by time dependent nature of recovery and by competing risks. our objective was to describe renal recovery, pattern of recovery according to adqi definitions and risk factor of this later. monocenter retrospective cohort study. adult patients admitted in our icu from july to december were included. aki was defined according to kdigo criteria and recovery according to adqi definition. incidence of recovery at each time point was depicted using competing risk survival analysis. risk of transition between aki and no-aki was assessed by a semi-markov model. last, a trajectoire analysis was performed to depict most frequent recovery patterns. results are reported as n (%) or median (iqr). results: patients were included with a median age of ( - ). median sofa score at admission was [ ] [ ] [ ] [ ] [ ] [ ] . at icu admission, patients ( . %) had an aki stage , patients ( . %) an aki stage and patients ( . %) an aki stage . according to adqi criteria, aki was defined as rapidly reversed in patients ( . % of aki patients), persistent aki in patients ( . %) and as acute kidney disease (akd) in patients ( . %), remaining patients couldn't be classified (n = ). risk of recovery was of % per day until day then % per day (fig. a) . fine and gray model, taking into account death as competing risk, identified risk factors negatively associated with renal recovery, namely sofa score (shr = . per point; % ic = [ . - . ]), preexisting hypertension (shr = . ; % ic = [ . - . ]) and aki severity (stage vs. stage shr = . ; % ic = [ . - . ]). risk of de novo aki was maximal during the first days and ranged from to % per day. trajectoire model identified clusters of patients ( fig. b) , closely associated with patients' outcome: a) low patients' severity and no or mild aki (n = ; hospital mortality: %); b) moderate to severe aki but little associated organ dysfunction (n = , hospital mortality: . %); c) severe aki and multiple organ failure (n = ; hospital mortality: . %). conclusion: this study, assessing aki recovery patterns, is the first to our knowledge using adqi definition. despite the high rate of early recovery and of rapidly reversed aki, up to % of aki patients had not recovered at day and could therefore be classified has having akd. compliance with ethics regulations: yes. rationale: sepsis is the most frequent cause of acute kidney injury (aki). the "acute disease quality initiative workgroup" recently proposed new definitions for aki, classifying it as transient or persistent. we aimed to determine the incidence, attributable mortality and host response characteristics of transient and persistent aki in patients with sepsis. patients and methods: we performed a prospective observational study comprising consecutive admissions for sepsis in intensive care units (icus) in the netherlands, stratified according to the presence and evolution of aki. attributable mortality fraction (excess risk for dying with persistent aki relative to transient aki) was determined using a logistic regression model adjusting for confounding variables. in a subset of sepsis patients, plasma biomarkers indicative of major pathways involved in sepsis pathogenesis were measured. in a second subset of patients, whole-genome blood-leukocyte transcriptomes were analyzed. results: sepsis patients were included. aki occurred in . % (n = ), of which . % (n = ) was transient and . % (n = ) persistent. patients with persistent aki had higher disease severity scores on admission than patients with transient aki or without aki and more frequently had severe (injury of failure) rifle aki-stages on admission (n = , . %) than transient aki patients (n = , . %, p < . ). persistent aki, but not transient aki, was associated with increased mortality by day- (adjusted or . , % ci . - . ; p = . ) ( figure) and up to -year (adjusted or . , % ci . - . ;p = . ). the attributable mortality of persistent relative to transient aki by day- was . % ( % ci . - . %). persistent aki was associated with enhanced and sustained inflammatory and procoagulant responses during the first days, and a more severe loss of vascular integrity compared with transient aki. baseline blood gene expression showed minimal differences with respect to the presence or evolution of aki. conclusion: persistent aki is associated with higher sepsis severity, sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient aki, and independently contributes to sepsis mortality. compliance with ethics regulations: yes. rationale: to address the paucity of data on the epidemiology of patients admitted to intensive care units (icus) with in-hospital cardiac arrest (ihca), we examined key features, mortality and trends in mortality in a large cohort of patients admitted in french icus over the past years. patients and methods: from to database of the collège des utilisateurs de bases de données en réanimation (cub-réa), we determined temporal trends in the characteristics of ihca, patients' outcomes and predictors of icu mortality. results: of the icu admissions, ( . %) were cardiac arrests and were ihca ( . %). during the study period, the age of ihca patients increased by . years (p = . ) and patients presented more comorbidities (chronic heart disease, chronic kidney disease and cancer). patients were also more critically ill over the period as reflected by the increase of saps-ii by . % (p < . ). paradoxically, in-hospital management became lighter through the time with reduced respiratory support (p < . ), renal support (p < . ) and use of vasoactive drugs (p < . ). crude in-icu mortality decreased from % to . % over the past eighteen years (p < . ), fig. rationale: in surgery, prophylaxis antibiotic aims at preventing the occurrence of post-operative infections. for adults, it is currently recommended to only use prophylactic antibiotic therapy during the time of the intervention. but in pediatric cardiac surgery, there is no consensus around the optimal duration of use of antibiotic prophylaxis. the protocol was modified in in the icu and its time reduced to h. we aimed to determine whether h of post-sternotomy antibiotic prophylaxis was not less effective than h treatment to help prevent care-associated infections. patients and methods: after agreement of the ethics committee of our institution, we performed a retrospective non inferiority study, with an inferiority margin to %. the primary objective is to compare the incidence of care-related infections between a second-generation cephalosporin (c g) antibiotic prophylaxis during h and a -h protocols. the secondary objectives are to determine the infection's incidence, to identify the risk factors for nosocomial infections and to compare the incidence of multidrug-resistant infections. results: between january and july , children underwent cardiac surgeries with sternal opening. received h of c g antibiotic prophylaxis and received h of c g treatment. five previously infected children have been excluded. both groups were demographically and surgically similar. the median age was months (range a few hours of life to . years old) and the median weight was . kg. in the intent-to-treat analysis, incidence of care-related infections is at . % in the c g- h group and . % in the c g- h group. a multivariate analysis shows that the shorter -h time antibiotic prophylaxis is not inferior regarding infection prevention compared to h of antibiotic prophylaxis, p = . . as in the per protocole analysis, the c g- h group rate was . % and . % for the g g- h group. conclusion: it demonstrates that shortening the antibiotic prophylaxis treatment time to h does not affect or increase the rate of infections after a pediatric sternotomy surgery compared to -h protocole. prophylaxis in pediatric cardiac surgery should be short-lived. a multicenter prospective study would allow a consensus and confirm this decision. compliance with ethics regulations: yes. rationale: the use of "big data" is getting increasingly popular in the medical field, especially in intensive care where large amounts of data are continuously generated. however, big data can be misleading when essential clinical data are missing. the adequate adjustment for potential confounding factors (e.g., severity of respiratory distress) should be the key procedure in the big data analyses; however, it is challenging to capture the clinical severity within large electronic databases. bronchiolitis is one main reason for admission to pediatric intensive care unit (picu). the modified wood's clinical asthma score (mwcas) is widely used to assess the severity of bronchiolitis. the objective of the study is to build an automated mwcas (a-mwcas) to continuously assess the severity of respiratory distress in critically ill children. this retrospective study included all infants < years old with a clinical diagnosis of bronchiolitis, ventilated with non-invasive neurally adjusted ventilatory assist, in a canadian picu, between october and june . we developed an algorithm, using python . , which was directly connected to the electronic medical record. the components of the score were collected using structured query language (sql) queries and processed to derive the a-mwcas. for validation, the a-mwcas score was compared to the mwcas manually computed by a clinical expert (m-mwcas) . results: sixty-four infants were included in the study, for which of a-mwcas and m-mwcas were generated respectively. the cohen's kappa coefficient was applied to estimate the agreement between the two scores which was . ( % confidence interval) ( table ) which corresponds to . % of complete agreement. . % of the a-mwcas scores were within ± . of the m-mwcas. the kappa coefficient for the each score component were: . for the oxygen saturation, . for the expiratory wheezing, . for the inspiratory breath sounds, . for the use of accessories muscles and . for the mental status, respectively. discussion: the largest discrepancy was observed in the mental status, which clinical evaluation is relatively subjective and varies among care team members (doctor, nurse, respiratory therapist…). the automated score likely decreases this variability by consistently using the same source (respiratory therapist), but its validity should be confirmed in a prospective study. the a-mwcas provides a valid estimation of the mwcas that is fast and robust. after external prospective validation, it may help to add some clinical sense within large electronic databases, with improved assessment of the respiratory distress. compliance with ethics regulations: yes. rationale: in paediatric intensive care units (picu), survival rates have dramatically improved. this has been accompanied by increased morbidity, including psychological morbidity. these new impairments, that can affect the survivors and their families have been conceptualized under the frame of post-intensive care syndrome (pics) and picsfamily. the aim of this study was to explore the experience of critically ill children parent's during the stay in picu, and its impact on the family. patients and methods: we planned a prospective, single centre study for months. we collected qualitative written data from parents whose child had been admitted to the picu for the first time, for at least two nights. results: fifty-seven questionnaires were analysed from thirty-seven admissions. picu admissions were mostly unplanned. among parents % experienced very painful memories during admission and % have feared for their child's life. during the stay, noise has bothered % of parents, and many have described difficulties to rest at night. % had the sensation that their child was suffering, mostly from pain, tiredness, anxiety or fear. during picu stay, % of parents had to stop working, and siblings schooling was impacted in % of cases, % of parents considered themselves to be useful for their child and % have participated to nursing care. more than % were satisfied about information given and communication, % appreciated empathy and support from care givers. parents received support from family, friends, and also from other parents of hospitalized children. parents expressed relief ( %) and serenity ( %) to leave picu, % of them were in demand to meet picu staff again after discharge. conclusion: picu parent's experience is tough, and the impact on family is clear. these are known risks factors for pics. on a very positive note, parents seemed to be satisfied by family-centred care, and were able to preserve their parental role. however, there is still room for improvement of practices. compliance with ethics regulations: yes. the gut has been suspected to be involved in multiple organs dysfunction syndrome (mods) in the intensive care unit (icu). studies suggested a link between gastrointestinal dysfunction (gid) and outcomes. but these studies included very few patients and most of them were retrospective. patients and methods: this study is a secondary analysis of data from a previous study that included patients from french icus. gid is defined as the association of vomiting and constipation or diarrhea during the first week after icu admission. patients included were treated with vasopressors and mechanical ventilation. the first goal was to determine if gid is a risk factor of -day mortality in this population. secondary goals were to assess the impact of gid on nosocomial infections. results: among included patients, ( . %) had gid. by day- , ( %) of the patients with gid and ( %) of the patients without gid had died (odds ratio . [ . - . ]; p = . ). multivariable regression model did not show any association between gastrointestinal dysfunction and increased risk of -day mortality in patients (odds ratio . [ . - . ], p = . ). gastrointestinal dysfunction was strongly associated with other secondary outcomes ( table ). patients with gid had longer ventilation duration, icu length of stay and hospital length of stay. they also had more nosocomial infections, in particularly ventilator-associated pneumonia. this association still existed in a multivariable regression model for prediction of nosocomial infection including the same variables than the previous model (odds ratio . [ . - . ], p = . ). no association with day- mortality was observed. conclusion: gastrointestinal dysfunction was not a risk factor of day- mortality but was associated with an increased risk of nosocomial infection and an increased length of stay. this study is observational and no causality link can be done. however, our data suggest further studies on strategies aimed to limit gid. compliance with ethics regulations: yes. rationale: acute cholangitis (ac), a bacterial infection related to an obstruction of the biliary tree, may be responsible for life-threatening organ failure. however, little is known about the outcome and the predictive factors of mortality of critically ill patients admitted in icu for acute cholangitis. we aimed to describe characteristics of patients admitted in icu for ac and to analyze predictive factors of in-hospital mortality including the time to biliary drainage procedure. patients and methods: retrospective study of all cases of acute cholangitis admitted in french icus ( tertiary hospitals and non-ter- [ . ; . ] µg/l. % of patients (n = ) have positive blood culture, mostly gram negative bacilli ( %) and % producing extended spectrum beta lactamase enterobacteriaecae. at icu admission, persisting obstruction was frequent ( %) and therapeutic endoscopic retrograde cholangiopancreatography was performed in % of them. in a multivariable analysis, at icu admission, several factors were significantly associated with in-hospital mortality: sofa score (or = . [ % ic . ; . ] by point, p = . ), arterial lactate (or = . [ . ; . ] by mmol/l, p < . ), total serum bilirubin (or = . [ . ; . ] by umol/l, p < . ), obstruction nonrelated to gallstones (p < . ) and ac complications (liver abcess and/or pancreatitis) (or = . [ . ; . ] p = . ). in addition, time > h between icu admission and biliary drainage was associated to in-hospital mortality (adjusted or = . [ . ; . ] p = . ). conclusion: acute cholangitis is responsible for high mortality in icu. organ failure severity, causes and local complications of cholangitis are predictive factors of mortality as well as delayed biliary drainage. compliance with ethics regulations: yes. the united kingdom) were included (n = ). predictors of one-year mortality were retrospectively screened and tested on a single center training cohort. a predictive score was developed and tested on an independent multicenter cohort. results: four independent pre-transplantation risk factors were associated with one-year mortality after transplantation in the training cohort: age ≥ years (or = . , % ci = . - . , p = . ), pre-transplantation arterial lactate level ≥ mml/l (or = . , % ci = . - . , p = . ), mechanical ventilation with pao / fio ≤ mmhg (or = . , % ci = . - . , p = . ) and pretransplantation leukocyte count ≤ g/l (or = . , % ci = . - . , p = . ). a simplified version of the model was derived by assigning point to each risk factor: the transplantation for aclf- model (tam) score. a cut-off at points distinguished a high-risk group (score > ) from a low-risk group (score ≤ ) with one-year survival of . % vs. . % respectively (p < . ). the model and its simplified version were validated on the independent multicenter cohort. there was a significant difference between the high-risk and low-risk group with one-year survival of % vs. . % respectively (p < . ). conclusion: liver transplantation can be an effective treatment for critically ill cirrhotic patients with hepatic and extra hepatic organ failure provided patients are carefully selected and that they are transplanted at the optimal time in the intensive care. the tam score can help stratify post-transplantation survival and assist clinicians in the transplantation decision-making process at the bedside of aclf- patients. compliance with ethics regulations: yes. rationale: trans-thoracic echocardiography (tte) is commonly used in the initial management of patients with shock in icu. there is little published evidence for any mortality benefit. we compared the effect of echocardiography protocol versus standard care for survival and clinical outcomes. patients and methods: this randomized controlled trial included selected shocked patients (systolic blood pressure < mm hg and signs of organ hypoperfusion) randomized to early tte plus standard care versus standard care without tte. the primary outcome measure was survivalto days. secondary outcome measures included initial treatment and vasopressor weaning. results: consecutive subjects with circulatory shock (low systolic arterial blood pressure (sap) and signs of organ hypoperfusion) at the time of icu admission are included in the study. in the tte group: fluid prescription during the first h was significantly lower rationale: both the negative prognostic value and reversibility of left ventricular (lv) diastolic dysfunction in septic patients remain debated. the excess of mortality in septic shock patients with hyperdynamic profile has only been reported by small-size studies. accordingly, the primary objective of the prodiasys study was to assess the impact of lv diastolic dysfunction (and its severity) and of lv hyperkinesia echocardiographically identified during the initial phase of septic shock on -day survival. the secondary objective was to assess the potential link between lv diastolic dysfunction, cumulative water balance (on day ), and outcome. patients and methods: this was a multicenter, prospective, observational, cohort study. patients older than years hospitalized in icu for septic shock (sepsis- definition) were eligible. exclusion criteria were administration of inotropes, severe left valvular disease, constrictive pericarditis and moribund patients. in each patient, echocardiography was first performed within h after the diagnosis of septic shock and then daily until day , after vasopressor discontinuation, at icu discharge and on day or at hospital discharge, whichever occurred first. vital and biological parameters usually monitored for septic shock management were collected at each echocardiographic assessment. vital status was collected on day . associations between lv diastolic dysfunction or lv hyperkinesia and day- mortality were analyzed using a chi test. adjusted analyses were performed using logistic regression models, including variables known to be linked with the prognosis of septic shock (e.g., severity scores, delay of antibiotherapy). the relationship between the grade (i to iii) of lv diastolic dysfunction and -day survival were analyzed using a logistic regression model. the relationship between the presence of lv diastolic dysfunction and cumulated water balance on day were analyzed using a linear regression model adjusted on the body weight on admission. the relationship between the grade of lv diastolic dysfunction and cumulated water balance on day were analyzed using a linear regression model. diaphragm dysfunction and weaning induced pulmonary edema are two frequent causes of weaning failure but their coexistence and interaction have been poorly investigated. we hypothesized that diaphragm dysfunction may not induce a sufficient decrease in intra-thoracic pressure to increase venous return and generate a weaning induced pulmonary edema. we therefore investigated whether weaning induced pulmonary edema and diaphragm dysfunction are or not associated and evaluated the effect of diaphragm dysfunction on cardiac function and lung aeration during a spontaneous breathing trial (sbt). patients and methods: patients with readiness to wean criteria who had failed a first sbt were eligible. before and after a second sbt, diaphragm function was assessed by measuring the change in tracheal pressure induced by a bilateral phrenic nerve stimulation (ptr, stim), cardiac function (cardiac output, systolic pulmonary arterial pressure) was evaluated with echocardiography and lung aeration was estimated from the lung ultrasound score (lus). plasma protein concentration and hemoglobin were also sampled before and after the sbt. diaphragm dysfunction was defined by ptr, stim < − cmh o and weaning induced pulmonary edema was diagnosed in case of sbt failure associated with ) increase in plasma protein concentration or hemoglobin > % during the spontaneous breathing trial and/or ) early (e) over late peak diastolic velocity ratio > . or e over peak diastolic velocity ratio > . . results: fifty-three patients were included and / ( %) failed the sbt. diaphragm dysfunction was present in / ( %) of patients with weaning induced pulmonary edema, in / ( %) patients with sbt success and in / ( %) patients with other causes of sbt failure (p < . ). during the sbt, diaphragm dysfunction induced a significant increase in systolic pulmonary arterial pressure but no change in cardiac output. patients with diaphragm dysfunction had a higher lus as compared to their counterparts ( ± vs. ± , respectively, p < . ). conclusion: diaphragm dysfunction induces a loss of lung recruitment and a significant increase in systolic pulmonary arterial pressure during the sbt. coexistence of diaphragm dysfunction and weaning induced pulmonary edema is common in case of sbt failure but weaning induced pulmonary edema appears more likely to be involved than diaphragm dysfunction. compliance with ethics regulations: yes. rationale: diaphragmatic weakness in the intensive care unit (icu) is associated with poor outcome. prolonged mechanical ventilation is associated either with a decrease (atrophy) or an increase (supposed injury) in diaphragmatic thickness, both associated with prolonged weaning. shear wave elastography is a non-invasive technique that measures diaphragm shear modulus (sm), a surrogate of its mechanical properties. the aim of this study was to describe the diaphragm shear modulus during the icu stay and to describe its relation with diaphragm thickness. patients and methods: this prospective and monocentric study included all consecutive critically ill patients. ultrasound examination of the diaphragm (aixplorer; supersonic-imagine, aix-en-provence, france) was obtained by two investigatorsevery other day until icu discharge. demographics, diaphragm thickness, sm and outcomes were collected. a mixed model regression was used to study the relation between sm and diaphragm thickness. results: we enrolled patients from december st to june st, being invasively mechanically ventilated during the stay. diaphragm ultrasound evaluation was feasible in / ( %) patients. the duration of mechanical ventilation during the icu stay was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days with [ ] [ ] [ ] [ ] [ ] days spent on controlled mechanical ventilation. sm was . ± . kpa and diaphragm end-expiratory thickness was . ± . cm upon icu admission. increase and decrease ≥ % during icu stay occured in and percent of the patients respectively for diaphragmatic thickness, and in and percent of the patients respectively for diaphragmatic sm. diaphragm thickness over time was inversely correlated with diaphragm sm and with time spent under mechanical ventilation (table) . diaphragm sm over time was correlated with time spent under pressure support ventilation or under spontaneous breathing (compared to controlled ventilation) and with time spent under deep sedation. diaphragm sm was inversely correlated with age, sepsis, exposition to steroids (table) . no association was found between diaphragm sm and outcomes. discussion: our results are in line with the myotrauma concept, suggesting alteration in diaphragm mechanical properties associated with increased diaphragm thickness in critically ill patients. we hypothesize that this observation most likely reflects muscle injury and tissue infiltration with edema and inflammatory cells. conclusion: shear wave ultrasound elastography suggests that in critically ill patients, the increase in diaphragmatic mass is associated with an alteration in diaphragm mechanical properties as measured by sm. compliance with ethics regulations: yes. rationale: diaphragm dysfunction and intensive care unit (icu) acquired weakness (icu-aw) are associated with poor outcomes in the icu but their long term impact on prognosis and health-related quality of life (hrqol) is poorly established. this study sought to determine whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and icu-aw has a particular impact on two-year survival and hrqol. patients and methods: we used a previous cohort study conducted in our institution to follow up mechanically ventilated patients in whom diaphragm and limb muscle functions were investigated at the time of liberation from mechanical ventilation. diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < cmh o and icu-acquired weakness was defined by medical research council (mrc) score < . hrqol was evaluated with the sf- questionnaire. results: sixty-nine of the patients enrolled in the original study were included in the survival analysis and were interviewed. overall two-year survival was % ( / ): % ( / ) in patients with diaphragm dysfunction, % ( / ) in patients without diaphragm dysfunction, % ( / ) in patients with icu-acquired weakness and % ( / ) in patients without icu-acquired weakness. patients with concomitant diaphragm dysfunction and icu-acquired weakness had a poorer outcome with a -year survival rate of % ( / ) compared to patients without diaphragm function and icu-acquired weakness ( % ( / ) (p < . )). hrqol was not influenced by the presence of icu-acquired weakness, diaphragm dysfunction or their coexistence. conclusion: icu-acquired weakness but not diaphragm dysfunction has a strong negative impact on two-year survival of critically ill patients. the presence of diaphragm dysfunction appears more likely to be a determinant of early prognosis and does not appear to have a significant impact on long-term survival. compliance with ethics regulations: yes. rationale: influenza can lead to severe condition with acute respiratory failure and acute respiratory distress syndrome due to a massive pulmonary inflammatory in response to the viral invasion. lung bacteriobiota has been described to be associated with pulmonary inflammation in chronic respiratory diseases such as chronic obstructive pulmonary disease or cystic fibrosis. lung mycobiota has been poorly investigated despite the well-known role for fungi in numerous respiratory diseases. the aim of our study was to assess the prognostic value of lung bacteriobiota and mycobiota among critically ill influenza patients. patients and methods: we prospectively included influenza patients admitted to icu. sputum were stored a - °c. bacterial and fungal dna were extracted thanks to qiaamp ® powerfecal ® pro dna kit. s rrna gene v -v regions and its regions were amplified by pcr and sequenced on illumina miseq ® . taxonomic assignation was obtained by dada pipeline and microbiota analysis were performed according to day- mortality by the mean of phyloseq package on r . . software. results: thirty-nine patients were admitted to icu for influenza with sputa available and finally dna samples available after extraction. bacteriobiota alpha diversity was significantly lower among non-survivors than survivors when expressed by the mean of shannon index, simpson index or evenness (respectively p = . , p = . , p = . ). area under the curve to predict day- mortality was . , ci [ . ; . ] for shannon index, . ci [ . ; . ] for simpson index and . ci [ . ; . ] for evenness. β-diversity analysis also demonstrated significant differences between survivors and non-survivors (adjusted permutational multivariate anova, p = . ). nonsurvivors had a higher abundance of staphylococcus, haemophilus, streptococcus and moraxella. none of the fungal alpha-diversity index nor beta-diversity were significantively different between survivors and non-survivors. non-survivors had a higher proportion of candida albicans and malassezia but not of aspergillus. conclusion: the lung bacteriobiota profile, but not the mycobiota one, of critically ill influenza patients is associated with day- mortality and may be used to identify subjects with a poor prognosis at the time of admission. compliance with ethics regulations: yes. that takes into account the interaction between multiple cellular pathways. the pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. results: patients ( severe and moderate influenza patients) and healthy control subjects were included in the study. severe influenza was associated with upregulation in several neutrophilrelated pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (net) formation. the degree of upregulation in neutrophil-related pathways was significantly higher in severely infected patients compared to moderately infected patients. severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation, cd + t-cell co-stimulation, cd + t cell and natural killer (nk) cells effector functions. apoptosis pathways were also downregulated in severe influenza patients compared to moderate and healthy controls. conclusion: these findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection. compliance with ethics regulations: yes. rationale: herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ards). however, few is known about herpes simplex virus (hsv) and cytomegalovirus (cmv) reactivation occurring in patients with severe ards under venovenous extracorporeal membrane oxygenation (ecmo). we tried to determine the frequency of herpesviridae reactivation and its impact on patients'prognosis during ecmo for severe ards. patients and methods: we conducted an observational, retrospective study in a medical icu (ards and ecmo referee center) between and . patients with a severe ards requiring a venovenous ecmo for days or more were included. hsv and/or cmv reactivation occurring after ecmo insertion was screened for these patients. patients with immunosuppression, antiviral therapy against hsv and/ or cmv prior to inclusion, or hsv/cmv reactivation known at the time of ecmo insertion were excluded. hsv reactivation was defined by a positive qualitative throat sample (virocult ® ) pcr or positive bronchoalveolar lavage (bal) pcr. cmv reactivation was defined by a positive quantitative blood or bal pcr. results: during a five-year period, non-immunocompromised patients with a severe ards necessitating a veno-venous ecmo were included. sixty-seven ( %) experienced hsv and/or cmv reactivation during ecmo course ( viral co-infection, hsv alone and cmv alone). hsv reactivation occurred earlier than cmv after the beginning of mv ( ( - ) vs. ( - ) days; p < . ) and after ecmo implementation ( ( - ) vs. ( - ) days; p < . ). in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation ( ( - . ) vs. . ( - ) days; p < . ), a longer duration of . ) vs. ( - ) days;p < . ), and a prolonged vs. ( - ) days; p < . ) and hospital stay ( ( - . ) vs. ( - ) days; p < . ). however, in multivariate analysis, viral reactivation remained associated with prolonged mv only. when comparing patients having cmv (alone or combined with hsv) vs. hsv reactivation alone, cmv positive patients had a longer mechanical ventilation duration and fewer ventilator-free days at day- and a longer icu and hospital length of stay. conclusion: herpesviridae reactivation is frequent among patients with sevre ards under veno-venous ecmo and is associated with a longer duration of mechanical ventilation. cmv seems to have a proper negative role on pulmonary fiunction as compared to hsv alone. hsv and cmv deserve to be researched in severe ards patients under ecmo. compliance with ethics regulations: yes. charlotte vandueren , benjamin zuber , eve garrigues , antoine gros , nicolas epaillard , guillaume voiriot , yacine tandjaoui rationale: respiratory syncytial virus (rsv) is a common cause of pediatric bronchiolitis and influenza-like illness in adults. its involvement in severe infections in adults remains unclear. the captif study aimed at comparing characteristics and prognosis of icu patients infected with rsv and influenza, assuming that, based on the limited evidence, the mortality of rsv infection would be lower than the influenza related one. patients and methods: multicenter franco-belgian retrospective study. adults admitted to icus between /nov/ and / apr/ with respiratory rsv infection were included and matched : to influenza patients on center and icu admission date. patients' characteristics, clinical presentation, and outcome were compared between groups using univariate and multivariable analyses. results: we report here the results for the first cases among included patients. mean age was . ( . ) years and saps- score was ( ), not different between groups. compared to influenza patients, rsv patients more frequently had chronic respiratory failure ( % vs %, p < . ) or immune suppression ( vs %, p = . ). frequencies of cardiac, renal and hepatic chronic diseases were similar. almost all patients had respiratory symptoms (> %), extrarespiratory symptoms were more frequent in influenza patients ( vs %, = . ). rsv patients more frequently had bronchospasm ( vs %, p = . ). clinical presentation such as ards ( %), shock ( %) and pulmonary coinfection ( %) were similar, however sofa score was higher in rsv patients ( . ( . ) vs . ( ), p = . ). the p/f ratio was around mmhg in both groups, paco was higher in rsv patients ( vs mmhg, < . ). respiratory assistance at diagnosis tended to differ (p = . ), rsv patients receiving more non invasive ventilation ( vs %) and less high flow oxygen therapy ( vs %) but invasive ventilation was required similarly ( vs %). during icu stay, ards was more frequent in rsv patients ( vs %, p = . ), accordingly prone position ( . vs . %) and ecmo ( . vs . %) were more frequently needed. length of mechanical ventilation ( days ( - ) ) and icu los ( days ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ) were not different. icu mortality was similar in rsv and influenza patients ( . % and . %), the multivariate analysis did not find an association between type of virus and mortality. conclusion: rsv infection is frequent in adult icu patients. it presents more frequently than influenza as an acute on chronic respiratory failure with bronchospasm. despite difference in case mix and clinical presentation, vrs severity and burden appear similar to influenza justifying effort to prevent and treat it. compliance with ethics regulations: yes. rationale: mortality in acute stroke patients requiring mechanical ventilation ranges from to % at year. studies evaluating indicators of outcome in these patients have limitations, including singlecenter, retrospective designs and no adjustment for withholding/ withdrawal of life-sustaining treatments (wlst). our objective was to identify factors associated with -year survival in acute stroke patients requiring mechanical ventilation. patients and methods: retrospective analysis of a prospective multicenter database between and . icu stroke patients entered in the database and requiring mechanical ventilation within h were included. were excluded patients with stroke of traumatic origin, subdural hematoma or venous cerebral thrombosis. factors associated with -year survival were identified using a cox model stratified on inclusion center, adjusted on wflst occurring during the first h. data are presented as median [q -q ] or percentages. cox model results are presented as hazard ratios (hr) and % confidence intervals (ci). results: we identified patients from icus, aged [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] years and % males. on admission, the glasgow coma score (gcs) was [ ] [ ] [ ] [ ] [ ] [ ] and the saps score was . types of strokes were ischemic ( %), hemorrhagic ( %) and subarachnoid hemorrhage (sah) ( %). ischemic stroke patients received thrombolysis or thromboaspiration in / ( %) cases, and hemorrhagic stroke/ sah patients received neurosurgery or embolization in / ( %) cases. reasons for endotracheal intubation were coma ( %), acute respiratory failure ( %), seizures ( %), cardiac arrest ( %) and elective procedure ( %). sixty-five ( %) patients received a decision of wflst in the first h. one-year survival year was %. variables independently associated with -year survival were stroke type (ischemic as reference, hemorrhagic hr . (fig. ) . inclusion period ( inclusion period ( - inclusion period ( / inclusion period ( - inclusion period ( / inclusion period ( - or having a stroke unit on site was not associated with -year survival. conclusion: in acute stroke patients requiring mechanical ventilation, the reason for intubation and the opportunity to receive a specific stroke therapy are independently associated with long-term survival. these variables should be integrated in the decision process regarding initiation of mv in acute stroke patients. compliance with ethics regulations: yes. rationale: international guidelines recommend targeted temperature management (ttm) between ° and °c for out-of-hospital cardiac arrest (ca) patients. however, it is unknown if this treatment is effective whatever the severity of the insult. we aimed to examine the association between ttm and long-term neurological outcome according to the risk evaluated at time of admission in intensive care unit (icu) using a dedicated and validated score. patients and methods: we used data prospectively collected in the sudden death expert center (sdec) registry (great paris area, france) between may and december and in the resuscitation outcome consortium-continuous chest compression (roc-ccc) between june and may . we used a modified version of the cardiac arrest hospital prognosis (mcahp) score to assess the risk of poor outcome at icu admission in each of datasets. we finally studied the association between ttm use and long-term neurological prognosis according to mcahp score at icu admission divided into tertiles of severity in each of the datasets. results: there were patients analyzed in the french dataset and in the north-american dataset. the mcahp identified categories: low risk (score < points, % of unfavourable outcome), medium risk ( ≤ score < , % of unfavourable outcome) and high-risk group (score > , % of unfavourable outcome). according to the mcahp score at icu admission, ttm was associated with a better long-term neurological prognosis in patients with low risk (aor = . [ . - . rationale: acute ischaemic stroke is associated with a high risk of mortality, morbidity and healthcare-related costs. over the last decades new treatments, such as thrombolysis and thrombectomy, have been introduced. because of their further improvement, complications have been decreasing. this also led to extending indications for treatment to patients who were previously not eligible. the impact of this evolution on long-term outcome and cost-effectiveness has mainly been assessed in clinical trials and simulation studies. patients and methods: this single-centre retrospective study included patients treated for stroke between january and february . functional outcome at days was assessed by the modified rankin scale (mrs). cost data were retrieved from individual invoices of patients. undiscounted total healthcare costs were calculated for the index hospital stay, capped at days. contribution of cost categories to total costs was analysed. mrs at days was used as a proxy for utilities to define quality-adjusted life years (qalys). multivariate analysis was done for gender, age, charlson comorbidity index, pre-stroke mrs, stroke severity (nihss) and treatment modality (thrombectomy, thrombolysis, thrombectomy + thrombolysis, no intervention). incremental cost-effectiveness ratios (icers), associated to each treatment modality, were calculated. results: no intervention was done in patients ( . %). patients ( . %) required thrombolysis, ( . %) thrombectomy and ( . %) the combination. total costs were mean , eur ) . hospitalisation costs (mean , eur, iqr - , ) represented % of total costs, compared with drug costs ( eur, iqr - ), procedural costs ( eur, iqr - ), honoraria ( eur, iqr - ), lab ( eur, iqr - ) and imaging ( eur, iqr - ). mean total costs differed between treatment modalities: , (iqr - , ) eur for no intervention, , ) eur for thrombolysis, , (iqr , ) eur for thrombectomy and , (iqr , ) eur for the combination (p < . ). drivers for total costs were treatment modality (p < . ) and nihss-stroke severity (p < . ). utility scores were . rationale: emergency endotracheal intubation (eti) in the intensive care unit (icu) often concerns hypoxemic patients with hemodynamic instability. a cardiovascular collapse (cvc) after eti is a life-threatening complication. french guidelines suggested systematic fluid loading prior to eti. our study aimed to predict cvc after eti, while using echocardiography, and to evaluate the impact of fluid loading. patients and methods: a prospective study of consecutive intubations was performed from june to november in three icus. patients were selected if mean blood pressure measurements ≥ mmhg before eti. cvc was defined as mean blood pressure < mmhg within min following eti. four echocardiographic examinations were performed: - min before and - min after eti (or when a cvc occurred); -after passive leg raising; - h following eti. patients were classified as fluid responders when the left ventricular outflow tract velocity-time integral increased by at least % compared with baseline. results: echocardiographic examinations were performed. cvc occurred in / procedures ( %). in cvc group, mean dose of diprivan, used for fast sequence induction, was higher ( . ± mg/kg vs . ± . mg/kg, p = . ). in the cvc group, fluid responsiveness was considered in % patients and left ventricular (lv) systolic dysfunction %. lv diastolic dysfunction did not concern any patient in the cvc group. systolic blood pressure (sbp) < mmhg was the sole independent risk factor for cvc occurrence in multivariate analysis: or . ci % . - . , p = . . fluid responsiveness independent risk factors for cvc patients was sbp < mmhg (or . , ci % . rationale: the autonomic nervous system is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of autonomic nervous system activity and a relation between hrv and outcome has been proposed in various types of patients. we attempted to evaluate the best determinants of such variation in survival prediction using a physiological data-warehousing program (reastoc clinicaltrials identifier nct ). patients and methods: physiological tracings were recorded at hz from the standard monitoring system (intelliview philips mp ) using the synapse software (ltsi inserm umr ), for a h period, during the h following icu admission. all measurements were recorded while patients were laying in bed, with the head at ° and without any medical intervention. physiological data were associated with metadata collection by a dedicated research assistant. hrv was derived using kubios hrv, in either temporal ( (sdnn), (rmssd) and triangular index (ti)), frequency ( (lf), (hf)), non-linear domains (poincaré plotting) and entropy. results: consecutive patients were recorded between may and april . a lower lf/hf (< . ) and sd /sd (< . ) ratios on admission were associated with a higher icu mortality. multivariate analysis enabled to develop a mortality predictive model (bicus) associating spo /fio and hrv parameters (lf/hf and shannon entropy) with an auc = . (p < . ) for a bicus value > (fig. ) . conclusion: hrv measured on admission enables to predict prognosis in the icu, independently of the admission diagnosis, treatment and mv requirements. bicus may help predict prognosis on a real time basis, using parameters derived from standard routine monitoring. compliance with ethics regulations: yes. rationale: stroke, in the context of type diabetes (t d) is associated with a worse outcome than in non-diabetic conditions, reflected by an increased ischemic volume and more intracerebral hemorrhage. an unbalanced diet is one of major risk for developing t d. we aimed at creating a reproducible mouse model of stroke in impaired glucose tolerance condition induced by high fat diet. patients and methods: adult c bl mice ( male and female) were fed for months with either high fat diet (hfd, % lipids, % proteins, % carbohydrates) or a normal diet (nd, . % lipids, . % proteins, . % carbohydrates) . we used a model of middle cerebral artery occlusion (mcao) by a monofilament for min. oral glucose tolerance test and insulin tolerance test were used for evaluating the pre-diabetic state. mice were euthanized h after reperfusion. systemic inflammation, cerebral infarct volume and hemorrhagic transformation were determined. results: hfd was associated with an increased glycaemia following the oral glucose tolerance test. plasma leptinlevels in stroke conditions were significantly higher in hfd vs nd group. the hfd group presented a significant increase of infarct volume (hfd: . ± . mm vs nd: . ± . mm p = . ) and hemorrhagic transformation (hfd: . ± . vs nd: . ± . p = . ) (fig. ) compared to nd group. discussion: in humans, one of the mechanisms leading to insulin resistance is low-grade inflammation. hfd increases gut permeability, which leads microbiota dysbiosis, thereby promoting metabolic endotoxaemia and a low-grade inflammation state. experimental mouse models available for diabetes studies use leptin receptor deficient mice which develop t d or destruction of pancreatic beta cells by streptozotocine injection (t d). studies using diet-induced insulin resistance models generally feed the mice for weeks or more. however, metabolic disorders could appear earlier such as increase inflammatory markers. in our model, a short exposition to hfd ( weeks) leads to an increase of the pro-inflammatory markers as plasma leptin and a more severe stroke status (infarct and hemorrhagic transformation). conclusion: two months of hfd in adult mice altered hyperglycemia control. this metabolic disorder was associated with significantly higher leptin production, increased infarct volume and hemorrhagic complications than in normal-fed mice. this new model is particularly relevant to study stroke under pre-diabetic conditions induced by hfd. compliance with ethics regulations: yes. eight weeks of hfd increase ischemic volume and hemorrhagic transformation. (a)-infarct volume (v) h after reperfusion, all value are mean ± sem, hfd: v = . ± . mm , n = , nd: v = . ± . mm , n = , *p = . (b)-hemorrhage transformation (ht) score h after mcao. all value are mean ± sem hfd: ht score = . ± . , n = , nd: ht score = . +/+ . , n = *p = . rationale: cardiac arrest (ca), as massive ischemia reperfusion (ir), is an universal health issue. medication taken at the time of the ca could have prognosis consequences. no medication has proven its benefit on ca prognosis. pharmacological pre-or postconditioning aims to reduce ir injury but with disappointing results. metformin (met) is a worldwide-prescribed antidiabetic drug, and several clinical reports plead for a potential protective effect in various settings of sterile and non sterile inflammation, including ir. our hypothesis is that met act as a preconditioning drug against ca-induced ir. patients and methods: retrospective single academic medical center survival study (french west indies) on resuscitated ca in icu (institutional ethical committee approval). data were extracted from medical charts, pmsi, and laboratory dbsynergy ™ software. anonymized data were entered on a excel ™ and transferred to ibm ® -spss ® software (v . . . ) for analysis. univariate study (chi- , fisher exact tests, student-t test, mann-whitney u-test if required) was followed by a multivariate model (odd ratio or and % ic: kaplan-meier estimator and non parametric logrank test-mantel cox model). assuming an overall in-hospital mortality for ca in icu of % with an expected mortality decrease of % by met, the number of patients to be included is . results: the inclusion period was to , with included patients ( diabetic patients among whom took met). the d mortality was % in met+ patients (n = ) versus % in nomet patients (n = ), p < . . comparing alive (n = ) versus deceased (n = ) at d in univariate then multivariate analysis, asystole on the first ekg, number of iterative cardiac arrest,sofa, no-flow, lactate, low-flow and sapsii appear as independent criteria associated with d mortality.conversely, met intake showed up as a protective criterion (or . , ci . - . ). the survival curve, including strata of low-flow duration at the cut-off min, is reported on the fig. . among diabetic patients (n = ), the mortality of patients in the met+ (n = ) was % versus % in the nomet (n = ), p = . . conclusion: in diabetic patients suffering of massive ir related to resuscitated ca, a current treatment by met is associated with a better survival. these results support a protective effect of met and are important to initiate prospective evaluations, because of millions diabetic people around the world and the potential benefit of met. the potential benefit in non diabetic patients and in sterile as well as non sterile inflammation should be addressed. compliance with ethics regulations: yes. rationale: during systemic inflammation, the accumulation of misfolded proteins in the endoplasmic reticulum (er) induces er stress (ers). in animal models, the inhibition of ers reduces inflammatory response and organ failure. cardiopulmonary bypass (cpb) induces a significant systemic inflammatory response but ers expression has never been described in cardiac surgery patients. our objective was to describe the variations of the glucose related protein of kda (grp ), the final effector of the ers, during cpb. patients and methods: we conducted a prospective monocenter study including patients undergoing cardiac surgery with cpb. two samples (paxgene ® tube + edta tube) were taken at three times: before cpb, h after the end of cpb (h -cpb) and h after (h -cpb). after rna isolation and reverse transcription, we performed a quantitative polymerase chain reaction to evaluate the expression of gene encoding for grp and determined the plasma level of grp using enzyme-linked immunosorbent assay. our main objective was to study the variation of grp between pre-cpb and h -cpb samples. our secondary objectives were to evaluate the association of ers with morbi-mortality: organ failure at h (catecholamines and/or invasive ventilation and/or acute renal failure), troponinemia and pao /fio ratio (lung damage control). fig. ). we found an inverse correlation between grp plasma level and troponinemia at h (r = − . ; % ci[− . ; − . ]; p = . ) and a correlation between the pao /fio ratio and grp plasma level at h (r = . ; % ci[ . ; . ]; p = . ). we showed a significant relationship between the variation in plasma concentration of grp and post-operative organ failure after cpb. further studies are needed to better understand the molecular mechanisms of ers in acute inflammatory organ failure in humans. compliance with ethics regulations: yes. patients and methods: in a retrospective monocentric study ( / - / ) conducted in cardio-vascular surgical intensive care unit (icu) in henri mondor teaching hospital, all consecutive adult patients who underwent peripheral va-ecmo were included, with exclusion of those dying in the first h. diagnosis of acute mesenteric ischemia was performed using digestive endoscopy, abdominal ct-scan or fist-line laparotomy. significative results in the univariate analysis were analyzed in a multivariate analysis using logistic regression. results: va-ecmo were implanted. median age was ( - ) years and median . va-ecmo was implanted after a cardiotomy in % of the cases and for a medical reason in % of the cases including % of refractory cardiac arrest. patients characteristics are reported in the table. acute mesenteric ischemia was suspected in patients, with a delay of ( - ) days after ecmo implantation. digestive endoscopy was performed in patients, ctscan in five patients and first-line laparotomy in three patients. acute mesenteric ischemia was confirmed in patients, i.e. an incidence of %. laparotomy was performed in six of the patients, two having a stage i colitis ischemitis with stable conditions and being considered too severe to undergo futile surgery. overall mortality was %. all the patients with acute mesenteric ischemia died in the icu. independent risk factors of developing acute mesenteric ischemia were renal replacement therapy , p = . )) and onset of a second shock state within the first days of icu stay (or . ( % ic . - . , p = . )). conversely, early enteral nutrition was negatively associated with acute mesenteric ischemia (or . ( % ic . - . ), p . ). conclusion: acute mesenteric ischemia is a relatively frequent condition among patients under va-ecmo for cardiogenic shock. its extremely poor prognosis requires low threshold of suspicion. compliance with ethics regulations: yes. ( ). it allows the computation of trans-pulmonary pressure ( ) and can be used to set positive end-expiratory pressure (peep) ( . ) . prone position(pp) can reduce mortality in patients with acute respiratory distress syndrome (ards), but peep selection in pp is controversial. in human ards end-expiratory pes at zero flow (peept,es) was not different between supine (sp) and pp at same peep ( ). as no study measured ppl in sp and pp in ards we aimed at comparing peept,es and end-expiratory ppl at zero flow (peept,ppl) in this condition. our hypothesis was that peept,es was close to dorsal peept,ppl (peept,ppldorsal) in sp and to ventral peept,ppl (peept,pplventral) in pp. in eight female pigs of kgs intubated, sedated, paralyzed and mechanically ventilated, ards was induced by repeated saline lavage until pao /fio < mmhg under fio and peep cmh o. pes was measured by nutrivent catheter. ppl was measured by custom-made pouch sensors inserted surgically into the right anterior and posterior sixth intercostal space. ppl sensors were filled with air. after ards induction animals were randomly assigned to sp or pp. in each position, a recruitment manoeuver was performed and peep decreased from to cmh o by steps of cmh o lasting min each, then the animals were crossed over into the alternate position where the same procedure was done. at the end of each step nonstressed volume and correct position (baydur maneuver) were determined for pes and ppl sensors, then a -s end-expiratory occlusion was performed and pes and ppl recorded. linear mixed model was used to compare the value of pes and ppl at each peep and position. results: box-and-whisker plots of pes and ppl in sp and pp are shown in fig. . there is marked dorsal-to-ventral gradient in ppl at each peep in sp, which is reverted in pp at peep and only. there was no interaction between pressures and peep or position. with increasing peep pes increased significantly from peep in sp and pp. peept,pplventral was significantly lower than peept,es in sp but not in pp. (medtronic) , carescape (ge)) were set in pressure support cmh o, peep cmh o, fio % and equipped with the same double limb ventilator circuit (intersurgical) without any humidification device. asl bench model was set with inspiratory/expiratory resistance (r) and compliance (c) combinations: r / -c , r / -c and r / -c mimicking normal, ards and copd conditions, respectively ( ) . inspiratory effort generated by asl consisted of consecutive breaths obtained from the esophageal pressure in a real patient at the time of a spontaneous breathing trial. for each icu ventilator and rc combination, two steps were performed: in the first, atc was not activated and ventilator attached to asl without ett (atc-ett-); in the second, atc was set on at % compensation for an ett mm id and such an ett (shiley hi contour, covidien) joined icu ventilator to asl (atc+ ett+). the null hypothesis is that vtatc+ ett+ minus vtatc-ett-is . primary end point was the breath by breath paired difference betwen atc+ ett+ and atc-ett-. it was tested to zero for each ventilator in each rc condition. results: median vt was ml. table displays mean (± sd) difference in vt (ml) between atc+ ett+ and atc-ett-: a negative value means that atc under delivers and a positive value that atc over delivers vt for a given patient's inspiratory effort and rc. in four ventilators (c , s , elisa and ) atc almost systematically under delivered vt. in several instances under compensation was greater than % median vt. by contrast atc performed better with the other three ventilators (evita xl, v and carescape ). conclusion: atc tended to under deliver vt. furthermore, there were marked differences between icu ventilators the clinician should be aware of when using the atc option. compliance with ethics regulations: na. rationale: during the last decades, identification of factors associated with ventilation-induced lung injury has led to improved survival in patients with ards. the mechanical power of ventilation is the total energy transmitted from the ventilator to the respiratory system per unit of time and comprises three different components: elastic related to peep, elastic related to tidal volume and resistive. this integrative variable has been recently proposed as an useful predictor of ventilationinduced lung injury and death among ventilated patients. our goal was to determine the respective impact of the total mechanical power and its three components on the outcome of patients with ards. patients and methods: we performed a post hoc analysis of a randomized, controlled study of patients with ards with a pao /fio ratio < . themechanical power at inclusion and averaged on the first days after inclusion (total and its three different components) was computed according to the following equation: powerrs (j/ min) = . respiratory rate tidal volume [peep ( ) + ½ driving pressure ( ) + (peak pressure-plateau pressure) ( )], where the ( ), ( ) and ( ) parts correspond respectively to the elastic related to peep, elastic related to tidal volume and resistive components. the association between each of these four types of mechanical power evaluated during the first days after inclusion and mortality at d was assessed one after the other through multiple logistic regression, allowing control for potential confounding variables at inclusion (age, igs score without age, group of randomization, pao /fio , arterial ph). results: data from patients were analyzed, among which ( . %) died before d . there was no difference concerning the mechanical power at inclusion between survivors and non survivors (either total or its three components). among the four different types of mechanical power tested during the first days after inclusion, the elastic component related to tidal volume was the only one that was independently associated with mortality at d (or . ; % ci . - . ; p = . ) (figure) . conclusion: our study shows that only the elastic component of the mechanical power related to tidal volume independently predicted mortality at d among patients with ards, whereas the total mechanical power, its elastic component related to peep and its resistive component did not. further studies are needed to better define how the mechanical power of ventilation could be useful to synthetize the risk of ventilation-induced lung injury. compliance with ethics regulations: yes. probability of death at d as a factor of mean value (on d -d ) of the elastic component related to tidal volume of the mechanical power. to examine the effect of early-stage mechanical ventilation (mv) on diaphragmatic contractility. in the nd step, if a diaphragmatic dysfunction was detected, we assessed its influence on the weaning from ventilator. patients and methods: we measured prospectively the ultrasounddiaphragmatic thickening fraction (dtf) between groups: a study group versus a control group (n = for each). the study group included all adult patients receiving mv, in whom, the dtf was measured within a minimum of h and a maximum of days of mv. for the control group, were enrolled after their approval for participation, adult volunteers in spontaneous ventilation (sv). patients with factors affecting the diaphragmatic contractility (neuromuscular disease, severe obesity, and neuromuscular blockers…) were excluded. the ultrasound measurements were obtained at the zone of apposition of the right hemithorax. teleinspiratory and telexpiratory diameters (tid/ ted) were taken on the medio-axillary lines: posterior, median and anterior. the dtf was calculated as following: dtf = (tid-ted/ted) x . at the st step, the dtfs were compared and at the nd step: the relationship between dtf and weaning was analysed. results: our groups were comparable in corpulence and co morbidities. the sv group was younger ( vs. years, p < . ) with a predominant female composition. the diaphragmatic exploration concluded that in the mv group, the mean tid tended to be higher but without significant difference ( . + versus . + mm, p = . ), the mean ted was significantly higher ( . + versus . + . mm, p = . ) and dtf was significantly lower ( . + . % versus + . %, p = . ). the ventilation mode had no effect on dtf ( . + % for control volume vs. . + % for psv mode, p = . ). fourteen among ventilated patients had a successful weaning with a mean duration of days. a negative correlation was found close to significance between dtf and weaning duration (rho = − . and p = . ). a dtf value > % wasassociated with weaning success (or = , % ci = [ . - . ] and p = . ) with sensitivity = . %, specificity = %, ppv = % and npv = %. conclusion: the diaphragmatic contractile function was altered from the first days of mv. weaning duration seemed to be negatively correlated with dtf, and a dtf at the first days of mv greater than % was predictive of weaning success. compliance with ethics regulations: yes. rationale: mechanical ventilation is a life-saving treatment that is however associated with lung injury and/or diaphragm dysfunction. the optimal ventilator settings to provide lung protective ventilation while maintaining safe diaphragm activity are difficult to determine. a noninvasive and bedside evaluation of the diaphragm activity could be helpful in this context. the present study investigated whether changes in diaphragm shear modulus (i.e. stiffness, Δsmdi) assessed by ultrasound shear wave elastography (swe) may be used as a surrogate of changes in transdiaphragmatic pressure (Δpdi) in mechanically ventilated patients. patients and methods: patients had to be ventilated for at least h without contraindications for the placement of an oeso-gastric catheter. pdi was monitored continuously and smdi was measured at the zone of apposition of the right hemi-diaphragm, at hz sampling rate. measurements were performed twice under initial ventilator settings and at the end of a weaning trial. pearson correlation coefficients (r) were computed to determine within-individual correlations between pdi and smdi and changes in pdi and in smdi occurring between initial ventilator settings and the end of the sbt were compared by a paired test. results: twenty-five patients were enrolled and displayed a significant correlation between Δsmdi and Δpdi (mean r = . , range = . - . , all p < . ) (fig. a ). compared to their counterparts, patients with significant within correlations had a lower respiratory rate ( . ± . vs . ± . breath/min. respectively; p < . ) and a significant increase in Δsmdi ( . ± . kpa vs . ± . kpa. p < . ) between initial ventilator settings and the sbt. patients without Δsmdi-Δpdi correlation only displayed an increase in Δpdi ( . ± . vs . ± . cmh o, p < . ) at the end of the sbt with no concomitant significant increase in Δsmdi ( . ± . kpa vs . ± . kpa, p > . ). (fig. b) . conclusion: smdi obtained by swe appears as a promising technique to assess diaphragm activity in mechanically ventilated patients but technological improvements are necessary to increase swe sampling rate before enabling its generalization in the icu. compliance with ethics regulations: yes. rationale: end-inspiratory (eip) and end-expiratory (eep) pauses are commonly used during volume assist control ventilation to assess plateau pressure and total positive end-expiratory pressure (peeptot). they can also be used during assisted ventilation (av) for muscle pressure assessment. it requires ventilators able to perform eip during av. plateau pressure (pplat) usually increases in av during eip due to "hidden" inspiratory effort. pressure muscular index (pmi) is equal to pplat minus the sum of peeptot (measured during an eep) and set pressure support (ps); it theoretically reflects patient's effort without esophageal pressure (pes) monitoring. pes is the gold standard method to assess inspiratory muscle pressure (pmus, difference of pes drop at neural end-inspiration and correction factor for chest wall elastance and tidal volume). we aimed to illustrate the feasibility of measuring pmi using a standard icu ventilator at the bedside and study the correlation between pmus and pmi. patients and methods: measurements were recorded in icu patients. pes was measured using an nasogastric probe (equipped with an esophageal balloon) inserted for advanced monitoring (severe acute respiratory distress syndrome-ards) or for a study protocol (difficult weaning after copd exacerbation). recorded eip, eep and pes were used for post hoc analyses. results reported as ranges and median [iqr] . correlation between pmus and pmi tested with spearman correlation test. results: out of eip and eep duos could be analyzed ( -esophageal spasm/ -calibration error). ventilator mode was pressure support ventilation (ps - cmh o). cmh o, pmus = . [ . - . ] cmh o, pmi = . [ . - . ]. for all recordings, spearman r coefficient between pmus and pmi was . (p = . ). conclusion: muscular effort can be assessed in av using eip and eep using icu ventilators. however, recordings can be influenced by expiratory muscles contraction. patient's ability to follow directions during the maneuvers is an important factor to obtain reliable values. there seem to be a correlation in our small sample between muscular pressure assessed without and with pes. compliance with ethics regulations: yes. rationale: severe pneumonia can culminate in acute respiratory distress syndrome (ards). an uncontrolled inflammatory response is a key feature favoring transition towards ards. however, the underlying mechanisms remain poorly understood. in this context, the contribution of "innate t cells" (itc) -a family of non-peptide reactive t cells comprising nkt cells, mucosal associated invariant t (mait) cells and γδt cells-has never been explored. itc have emerged as key players in orchestration of the host response during infections and inflammation processes. for these reasons, these cells are already seen as potential therapeutic targets in other medical fields (especially oncology). here, we hypothesized that a tight regulation of their functions could be paramount to control the inflammatory response and to prevent ards development. patients and methods: to explore this, we combined a murinemodel of influenza a virus (iav) infection mimicking ardssymptoms and a clinical study recruiting patients admitted in icu for severe pneumonia. using flow-cytometry approaches, we investigated ( ) the abundance and dynamics of itc in various compartments, ( ) their pattern of activation/regulation markers (respectively cd and pd- ) and ( ) their cytokine production. results: during experimental iav pneumonia, itc were transiently recruited into the airways. unlike γδt and nkt, mait cells phenotype was largely changed, displaying a progressive cd overexpression and increased il- a production. during the resolution phase, up to % of pulmonary maits expressed pd- (versus < % in controls), which can suggest emergence of regulatory functions. last, using gene-targeted mice, we suggested that mait cells confer a protective effect during pneumonia. in the ongoing clinical study, the proportion of circulating mait cells in patients was markedly decreased compared to controls ( . ± . % versus . ± . % of t cells), but not for nkt or γδt cells. notably, some patients with severe ards presented detectable levels of maits in their respiratory fluids. in addition, circulating mait cells in patients overexpressed cd and pd- ( . % and % respectively), but with a reduced proportion able to produce il- and ifnγ, compared to healthy controls. lastly, proportion of activated (cd +) mait cells significantly decreased with clinical improvement. conclusion: this translational approach combining in vivo animal experiments and clinical samples with ex vivo experiments indicates a preferential modulation in mait cells functions during severe pneumonia. these data justify an in-depth analysis of mait cells activation mechanisms and functions in this context, in order to further explore a potential use as a disease-progression marker and -in a long term perspective-as a potential therapeutic target. compliance with ethics regulations: yes. representative flow-cytometry dot-plots of mait cells labelling using fluorophore-conjugated mr tetramers loaded with -op-ru from lungs of an infected mouse (a) and blood sample of a patient with pneumonia (b). c: frequency of mait cells, proportion of cd and pd- + mait cells in bronchoalveolar lavage during experimental murine pneumonia. d: blood frequency of mait cells in patients with pneumonia compared with healthy controls (as % of total t cells) rationale: immune paralysis following hyperinflammatory states increases the risk of secondary infections and death. reversing t-cells exhaustion using recombinant il or immune checkpoints inhibitors may improve the prognosis of patients with sepsis admitted to the icu. however, there is an unmet need to better characterize the state of t-cells exhaustion in these patients, its reproducibility and its correlation with the outcomes before implementing immunotherapy in the therapeutic armamentarium against sepsis. patients and methods: prospective observational cohort study performed in two tertiary-care icus in a university hospital. peripheral blood mononuclear cells were collected at day in adult patients with sepsis admitted to the icu. the level of cd + and cd + t-cells exhaustion was quantified using multi-color flux cytometry targeting the following exhaustion markers: pd- , b and cd . cd + regulatory t-cells (cd + cd + cd hi cd lo cells) were also assessed. results: the patients included in the study could be split in five clusters according to their dominant pattern of exhaustion markers on cd + t-cell (i.e. no markers, pd- +, b +, b + cd + and b + pd- +) and independently of their underlying morbidities. no patients harbored a fully exhausted triple-positive pattern. by multivariate analysis, saps gravity score at day (p = . ), a dominant b and/or pd- cd + pattern (p = . ) and lung sepsis (p = . ) where associated with the risk of death at day , whereas hemoglobin level was associated with survival (p = . ). no cd + or cd + exhaustion pattern independently predicted the risk of secondary infections. neither the level of cd + regulatory t-cells nor the dominant cd + exhaustion pattern was associated with the outcomes. rationale: there is growing use of multiplex polymerase chain reaction (mpcr) for respiratory virus testing in patients with communityacquired pneumonia (cap). data on one-year outcomes in patients with severe cap of bacterial, viral and unidentified etiology are scarce. patients and methods: a single-center retrospective study was performed in intensive care unit (icu) patients with known one-year survival status who had undergone respiratory virus testing for cap by mpcr. one year after icu admission, mortality rates and functional status were compared in patients with cap of bacterial, viral or unidentified etiology. results: there were ( . %) patients in the bacterial group, ( . %) in the viral group and ( . %) with unidentified etiology. one-year mortality was . % (n = / ), % (n = / ) and . % (n = / ), respectively (p = . ). in multivariate analysis, one-year mortality was higher in the bacterial group than in the viral group (hr . , % ic . - . , p = . ), had a trend to be higher in the bacterial group compared to the unidentified etiology group (hr . , % ic . - . , p = . ) and was not different between the viral and unidentified etiology groups (hr . , % ic . - . , p = . ). severe dyspnea (mmrc score = or death), major adverse respiratory events (new homecare ventilatory support or death) and severe autonomy deficiencies (adl katz score ≤ ordeath) were observed in / ( . %), / ( . %) and / ( . %) patients, respectively, with no difference between groups. conclusion: cap of bacterial origin was associated with a poorer prognosis than viral or unidentified etiology. impaired functional status was observed in a substantial proportion at one-year, irrespective of the causative microorganisms involved. compliance with ethics regulations: yes. interest of unyvero multiplex pcr (curetis) for bal rapid microbiologic and antibiotic susceptibility documentations in immunocompromised patients under antibiotic therapy jean-luc baudel , jacques tankovic , redouane dahoumane , salah gallah , laurent benzerara , jean-remy lavillegrand , razach abdallah , geoffroy hariri , naike bige , hafid ait-oufella , nicolas veziris , eric maury , bertrand guidet rationale: our aim was to evaluate the interest of the unyvero rapid ( . h) multiplex pcr assay (performed on bronchoalveolar lavage [bal] samples) for the management of immunocompromised patients already treated with antibiotics and diagnosed with pneumonia (according to clinical and radiological findings). we thus performed an observational study that compared the results (and the length of time to obtain them) of routine microbiological evaluation and unyvero assay. patients and methods: from july to january and from april to august , we examined bal samples from immunocompromised patients (coming from hematology, oncology, hepatology, gastroenterology, internal medicine, and neurology units) diagnosed with pneumonia (based on clinical and radiological findings), and already receiving antibiotic treatment. the following data were collected: age, gender, saps score, lung ct scan ( %) or x-ray ( %) results, duration and content of prior antibiotic therapy, direct examination, culture, antibiogram and unyvero results, secondary confirmation of pneumonia or not, possible changes in antibiotic therapy that could have been made after obtention of unyvero results. informed consent was obtained from all patients. results: bal samples were analyzed in immunocompromised patients (m/f ratio . , saps . ± . ) mostly with hematologic ( %) or oncologic ( %) diseases. the patients received either corticosteroids ( %), or chemotherapy ( %), or immunotherapy ( %). % of the patients were under mechanical ventilation, % under optiflow. % presented a shock, % had aplasia or neutropenia, % were allografted, % were autografted. the duration of prior antibiotic therapy at the time of bal were . ± . days. direct examination was positive in . % of the cases, culture (both above and under the classical threshold of cfu/ml) in %, unyvero in . %. a retrospective analysis of all the cases confirmed the initial diagnosis of pneumonia in only % of the cases. compared to culture, the sensitivity of unyvero was %, its specificity %. unyvero could permit to rapidly deescalate antibiotic therapy in % of the cases and to rapidly stop it in %. the unyvero assay on bal samples is useful in this specific population for rapid obtention of microbiological results and also for confirmation of the negativity of cultures and thus permits a better management of antibiotic therapy, leading to a reduction of antibiotic resistance selection pressure in the icu. compliance with ethics regulations: yes. do not underestimate rsv pneumonia among critically ill patients erwan begot , suzanne champion , charline sazio , benjamin clouzeau , alexandre boyer , hoang-nam bui , marie-edith lafon , camille ciccone , julia dina , didier gruson , renaud prével chu bordeaux, medical intensive care unit, bordeaux, france; chu bordeaux, virology laboratory, bordeaux, france; national reference center for measles mumps and rubella, chu de caen, caen, france correspondence: erwan begot (erwan.begot@chu-bordeaux.fr) ann. intensive care , (suppl ):f- rationale: respiratory syncitial virus (rsv) is a well-known cause of respiratory failure among neonates but its pathogenicity in adults is now emerging as a potential cause of viral pneumonia. data are limited with conflicting results regarding rsv pneumonia severity in adults. data are lacking about critically ill rsv patients' characteristics and outcomes. the aim of this study is to compare rsv patients' characteristics, care and outcomes to influenza patients' ones. patients and methods: patients diagnosed with rsv and influenza pneumonia admitted to our medical icu were included. data were retrospectively recorded. quantitative data are expressed by median and interquartile range and compared by use of mann-whitney test. qualitative data are expressed by number and percentages and compared by use of fischer exact t-test. rsv strains were prospectively collected. results: eighteen critically ill patients with rsv pneumonia and with influenza pneumonia were included. rsv and influenza patients had the same characteristics at admission except for age (respectively yo [ ; ] and acute respiratory distress syndrome rates (respectively / ( %) vs / ( %), p = . ). they received similar treatment as suggested by oro-tracheal intubation rates (respectively / ( %) vs / ( %), p: . ) and antibiotics prescription (respectively / ( %) vs / ( %), p: . ). rsv and influenza patients also had the same rates of bacterial co-infections ( / ( %) vs ( %), p: . ). invasive aspergillosis remained a rare event but also occurred among rsv patients ( / ( %) vs / ( %), p: . ). acute coronary syndromes were as frequent in both groups (respectively / ( %) vs / ( %), p = . ). day- mortality was similar between rsv and influenza patients (respectively / ( %) rationale: respiratory distress from seawater drowning is commonly considered multifactorial. etiologies are debatable and include heart failure, infection and acute respiratory distress syndrome (ards). documented bacterial infections seems mostly related to the site of drowning. data in this regard are scarce with prospective studies lacking. the objective of our study was to describe prospectively the characteristics and determinants of respiratory distress from seawater drowning. patients and methods: all patients admitted for seawater drowning to seven intensive care units (icu) on the french riviera in the summers of and were prospectively included. recorded data included clinical features on examination, personal history, chest x-rays, echocardiography and biological results obtained within the first h. a paired student's t-test was used to study statistical differences between quantitative variables on admission and during early evaluation (i.e. first h). results: forty-eight patients were admitted to seven centers of which ( %) were diagnosed as having ards, ( %) early pneumonia and ( %) acute cardiogenic pulmonary edema. twenty-one ( %) respiratory samples were collected but bacterial culture was positive in only cases. multidrug-resistant bacteria were not observed, and amoxicillin-clavulanate as first-line treatment was effective in all cases. echocardiography performed in ( %) patients was normal and unable to identify specific patient profiles. the median clinical pulmonary infection score (cpis) on admission was (iqr, - ) and decreased rapidly and significantly (p < . ) within h to (iqr, - ) (fig. ) . conclusion: data from this multicenter cohort suggest that respiratory distress following seawater drowning can mimic bacterial pneumonia during the first h with subsequent rapid clinical improvement in patients admitted to the icu. probabilistic antibacterial therapy should therefore be limited to the most severe patients. isolate ards is often the only etiology found and is resolutive within h. this prospective cohort is the largest of its kind and gives a better insight into the limited impact of cardiogenic and infectious processes on sea drowning-related respiratory distress. compliance with ethics regulations: yes. rationale: patients treated with "extracorporeal membrane oxygenation" (ecmo) are at a higher risk of developing nosocomial infections and they are consequently often treated with beta-lactams. french guidelines recommend obtaining beta-lactam trough concentrations above four times the minimal inhibitory concentration (mic) of the causative bacteria. the ecmo device may alter the pharmacokinetics of these medications, which may result in underexposure to beta-lactam antibiotics. patients and methods: this observational, prospective, multicenter, case-control study was performed in the intensive care units of two tertiary care hospitals in france. ecmo patients with sepsis treated with piperacillin-tazobactam were enrolled. control patients were matched according to sofa score and creatinine clearance. the pharmacokinetics of piperacillin was described based on a population pharmacokinetic model, allowing to calculate the time spent above × the mic breakpoint for pseudomonas aeruginosa susceptibility after the first dose and at steady state between two piperacillin infusions. results: forty-two patients were included. the median age was years [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , the sofa score was [ ] [ ] [ ] [ ] [ ] [ ] , and median creatinine clearance was ml/min . there was no significant difference in the time above x mic in patients treated with ecmo and controls during the first administration (p = . ) and at steady state (p = . ). there was no significant difference between the trough at steady state (p = . ), with / patients ( %) exhibiting concentrations of piperacillin lower than x mic. ecmo support was not associated with a steady state trough concentration below x mic (or = . [ . - . ], p = . ). the only variable independently associated with this risk was a creatinine clearance ≥ ml/min, (or = . [ . - . ], p = . ). conclusion: ecmo support has no significant impact on piperacillin exposure. intensive care unit patients with sepsis are, however, frequently underexposed with piperacillin, which suggest that therapeutic drug monitoring should be strongly recommended for severe infections. impact of a visual support dedicated to prognosis of patients on symptoms of stress of family members rationale: family members commonly have inaccurate expectations of patient's prognosis. adding to classic oral information a visual support, depicting day by day the evolution of the condition of the patient, improves the concordance in prognosis estimate between physicians and family members. the objective of this study was to evaluate the impact of this support on symptoms of anxiety/depression of family members. patients and methods: we conducted a bi-center prospective beforeafter study. all consecutive patients admitted in the two icus were eligible. in the before period ( months), family members received classic oral information. in the after period ( months) , in addition to classic oral information, the visual support ( fig. ) was available for family members in the patient's room from the day of admission until discharge from the icu. at day and from admission, symptoms of anxiety/depression of referent family member were evaluated by hospital anxiety and depression scale (hads). results: patients and their referent family members were included ( in period before and after). characteristics of patients of the two groups were similar regarding age, reason for admission, saps ii at admission and sofa score at day . also characteristics of referent family members were comparable in terms of age, sex ratio, type of relationship with the patient and number of visits since admission. at day , total had score was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the group before without the support and [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the group after with the support (p = . ). the prevalence of symptoms of anxiety (had-a score > ) and depression (had-d score > ) was similar in the two groups (respectively . % and . % in the group before, and . % and . % in the group after (ns)). at day , total had score was in the group before [ - ] and [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the group after (p = . ). by multivariate analysis the following factors were significantly associated with total had score > at day : age of patient ]), number of visits of referent ) and previous or current treatment of referent for anxiety or depression . ]). conclusion: in this study, the use of a visual support dedicated to prognosis of patients did not modify the level of stress of family members. compliance with ethics regulations: yes. rationale: the use of sedation and opioids at the end of life is a topic of considerable ethical debate. incidence of discomfort during the end-of-life of icu patients and impact of sedation on discomfort are poorly known. patients and methods: post-hoc analysis of an observational prospective multicenter study comparing terminal weaning vs. immediate extubation for end-of-life in icu patients, aimed at assessing the incidence of discomfort events according to levels of sedation. discomforts including gasps, significant bronchial obstruction or high behavioral pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. level of sedation was assessed using the richmond agitation sedation scale (rass). results: among the patients included in the original study, ( %) experienced discomfort after mechanical ventilation withdrawal. patients with discomfort received lower doses of midazolam and equivalent morphine, and less frequently had deep sedation (rass - ) than patients without discomfort ( % vs %, p < . ). after multivariate logistic regression, immediate extubation was the only factor associated with discomfort whereas deep sedation and administrations of vasoactive drugs were two factors independently associated with no discomfort. death occurred less rapidly in patient with discomfort than in those without discomfort ( . h [ . - . ] vs . [ . - . ], p < . ) (figure) . long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others. discussion: despite the theoretically expected anticipatory titrated doses of opioids and benzodiazepines to alleviate any discomfort after withdrawal of mechanical ventilation, half of the patients did not receive sedation or opiate when the decision to withdraw mechanical ventilation was taken. a major point that could interfere with the continuous deep sedation practice until death is the fear of potentially hastening death, and there is much controversy regarding its proper use in end-of-life care. conclusion: discomfort was frequent during end-of-life of icu patients and was mainly associated with terminal extubation and less profound sedation. compliance with ethics regulations: yes. rationale: bereavement in intensive care unit (icu) is associated with psychiatric disorders on relatives called post-intensive care syndrome family (pics-f). no isolated intervention (such as condolence letter) has shown a positive effect on these disorders, despite a well acceptance by relatives. we thought that a more integrated bereavement program should be considered. the goal of this study is to evaluate a combined psychologist-physician post-death meeting (pdm) in a bereavement program to evaluate needs and adhesion of relatives, and the effect on symptoms of anxiety and depression. patients and methods: monocentric, prospective study focused on relatives of patient admitted > h and deceased in icu. during patient's stay, relatives' presence was allowed on a h-basis and they could meet a clinician psychologist. formal meeting between relatives and the staff was realized at patient's admission and after important decision-making treatment. two weeks after patient's death, the psychologist called relatives to offer emotional support and to invite to a pdm. pdm occurs weeks after patient's death with the psychologist and the physician in charge of the patient. the objectives of the meeting were to provide emotional support, to answer medical question, and to detect symptoms of anxiety and/or depression with the hospital anxiety and depression scale (hads). we hypothesized that pmd would be able to alleviate pics-f at months. we aimed to enroll families to detect a % lowering of hads. results: the rate of pdm acceptance was lower than expected. after inclusions, only relatives accepted the pdm, whereas the phone call was well perceived ( %). main association with acceptance of pmd was a short duration of icu stay ( . days [ - . ] vs . days [ . - . ] p = . ) and icu admission for acute respiratory failure ( . % vs . %, p = . ) ( table ) . we found no relation between the number of in icu meeting (psychologist of medical staff) and pmd acceptance. for relatives who accept pmd we found a high proportion of symptoms of anxiety and depression ( % and %) with a hads at . [ - . ] (median, iqr). no evaluation was performed at months. conclusion: post death contact appears well perceived by relatives but pmd quite useless. this result may be explained by the inclusion of only late death (> h) where psychologist and medical staff had the opportunity to support relatives. further study should focus on early death (< h). compliance with ethics regulations: yes. rationale: pediatric intensivists frequently question themselves on the issue of limitation or termination of life-sustaining treatments (llst) carried out on children. such a decision comes under the claeys-leonetti law which forbids doctors from applying unreasonable treatment however, every so often, parents oppose themselves to a collegial llst decision that the medical and paramedical team had taken. such cases can even end up in court. in order to sort out this problem, this study focused on the factors that underlie the disagreement and the solution brought forward by pediatricians whenever parents demand to persue treatments although considered as unreasonable obstinacy. patients and methods: we carried out a qualitative study involving three multipurpose pediatric critical care unit. all pediatricians operating within these units were contacted. those who volonteered were met individually for a semi-directed interview. every interview was recorded and entitled to a complete hand-written retranscription. the interviews were analysed following the phenomenological interpretive analysis method and were subject to dual listing. results: pediatricians out of took part in the study. / claimed they would increase treatments or carry out cardiopulmonary resuscitation acts if asked to do so by parents, even if this went against the initial collegial decision. / claimed they would persue treatments although not beyond the current level. / said they would oppose themselves to parents concerning blood transfusion for comfort reasons. several key factors were identified as leading a doctor to the non-application of a llst decision: the certainty regarding the child's death on a short or mid-term basis ( / ), the litigiousness risk ( / ), the apprehension of mediatic pressure ( / ), the fear of a violent reaction from parents ( / ), other self-interest positions within the medical team ( / ), empathy towards parents ( / ), the uncertainty concerning the neurological prognosis ( / ), the lapse of time needed to fully accept the application in force of a decision ( / ). pediatricians out of admitted their own-suffering when confronted to the situation. conclusion: this study points out that pediatricians tend to follow parents' position when confronted to parental opposition. in such situations, pediatricians go against their own decision in order to safeguard the parental alliance even if it leads to unreasonable obstinacy, thus conflicting with medical deontological code obligations. compliance with ethics regulations: yes. rationale: end-of-life management strategies are clearly a worldwide issue of major importance that intensivists have to deal with on a daily basis. advance directives may be the solution sought to guide physicians to take such difficult decisions. yet, health care directives are not legislated in tunisia. the objective of this project was to draw a general descriptive overview to assess patients' wishes in tunisia. patients and methods: data were collected from a -item-questionnaire based on the french intensive care society's form for advance directives which was filled by people of general population in tunisia, including doctors and paramedics, from may to mid-september . all people included were or older and well informed of the form's utility. results: a total of participants were included. the mean age was . ± . years with extremes of and and a sex ratio of . . fourty-one ( . %) were either doctors or nurses and ( %) did suffer from a severe medical condition. among all the participants, ( . %) thought that end-of-life decisions were up to the doctor. for the rest, they willingly chose to be hospitalized in an icu, to undergo cardiopulmonary rescuscitation and to have ventilation support with orotracheal intubation or tracheostomy respectively in ( . %), ( . %) and ( . %) of the cases. only ( . %) refused temporary dialysis. when asked about sequelae they can live with, participants accepted hemiplegia in . % and paraplegia in . % of the cases. on the contrary, ( . %) refused to live in permanent coma and ( . %) disagreed to undergo tracheostomy and ventilation for life. moreover, ( . %) found that serious un aesthetic sequelae was a fatal consequence they could not survive. as well, only ( . %) consented to live with deep intellectual deficiency. regarding palliative care, ( . %) participants wished to be profoundly sedated until death, ( . %) prefered to die home over ( . %) in hospital. sixtytwo ( . %) desired to see a representative of their religion. furthermore, ( %) were for organ donnation. gender, being a health care professional and age under versus equal or over were not significant in dependent factors (p > . ). conclusion: it is our duty ashealth care professionals to spread advance directives awareness and education. nevertheless, the law should keep the pace with ethics evolution. compliance with ethics regulations: yes. rationale: adapted organ support techniques are needed to enhance reliability of preclinical animal experiments in the intensive care setting (guillon, annals of intensive care- ). a few renal replacement therapy (rrt) models have already been developed in rats, mostly hemodialysis in chronic kidney disease models or hemofiltration techniques in sepsis experiments. mounting evidence from clinical (gaudry, nejm- ) and histopathological studies suggest that rrt for acute kidney injury (aki) could impair renal recovery by acting as a 'second hit' leading to a maladaptive repair of tubular epithelium. we aimed to study this hypothesis in a hemodialysis model in rats with septic aki. patients and methods: on day , sprague-dawley rats were injected with lipopolysaccharide or placebo (nacl . %) intraperitoneally. on day , anesthetized rats underwent femoral artery catheterization for hemodynamic parameters monitoring. at the same time, one femoral vein and one carotid artery were catheterized for arterio-venous sterile extracorporeal circulation with or without passing through a miniature sterile polyester sulfone hemodialyzer ( cm surface, kda pores, microkros ® ) filled with dialyzate liquid in the outer compartment (table ) . vessels were ligated after the procedure and rats allowed to awaken. on day , rats were sacrificed. results: all rats injected with lipopolysaccharides o :b mg/kg survived at day . anesthesia was much challenging: ketamine + xylazine and tiletamine-zolazepam + xylazine required induction and maintenance intraperitoneal injections. these medications induced important hemodynamic parameters fluctuations and high mortality. isoflurane gas inhalation enabled better stability, less hypothermia and quick awakening. adequate temperature was controlled with a heating pad during the procedure and an incubator after. supine position was maintained. the whole circuit was anticoagulated with ml of heparinized saline ui/ml, since clots occurred in the absence of anticoagulation and bleeding when higher dosing was used. circuit (< . ml including dialyzer) was filled with saline solution before initiation, and total restitution of blood at the end of the experiment prevented any blood transfusion requirement. hematocrit was determined at beginning ( %) and end of experiment ( %). a peristaltic pump provided a blood flow rate of . ml/min, (higher rate was not tolerated) for h. of note, rats who underwent sham procedure (vessels ligature only) survived and did not display aki. circulation of a counterflow dialysate in the dialyzer is planned but has not been performed yet. conclusion: this hemodialysis system for rats is feasible at a reasonable price and might help research involving rrt in either ckd or aki. compliance with ethics regulations: yes. there were no significant relationship between rri and past medical history or severity score. we observed a significant negative correlation between rri and diastolic arterial pressure (p = . ) and heart rate (p = . ) as it could be expected by rri formula. an increased rri was associated with higher potassium (p = . ) and higher creatinine levels (p = . ). although not significant, we found a higher rate of subsequent rrt in the high rri group ( % vs %, p = . ). over the first days, fluid balance was significantly different between groups ( ml vs - ml respectively for low and high rri group, p = . ). since standard of care were similar, this suggests different fluid volume status between the two groups. in the low rri group, the cause of aki could predominantly be prerenal since positive fluid balance was not explained by more severe aki with refractory oliguria as shown by the low rrt rate. nevertheless, we did not observed any relationship between rri and the evolution of serum urea or creatinine levels, nor with the presumed aetiology of aki. conclusion: when focussing on the first rri measurement once stage aki was reached, rri ≤ . seems to be in favour of prerenal and transient renal dysfunction even if this is not supported by creatinine serum evolution. compliance with ethics regulations: yes. rationale: critically ill patients are at higher risk of bleeding but also dialysis filter clotting (inflammatory state). intermittent hemodialysis with calcium-free citrate-containing ( . mmol/l) dialysate (cafcit-ihd) recently emerged as a new safe and simple alternative to continuous renal replacement therapy allowing heparin-free extended dialysis sessions (> h). in this study, we aimed to answer to two issues still unresolved: (i) can citrate contained in the dialysate accumulate and lead to citrate intoxication in patients with liver disorders, and (ii) can citrate be avoided using citrate-and calcium-free dialysate (ccf-ihd)? patients and methods: monocentric retrospective study. among the sessions performed with cafcit-ihd, the ihd sessions ( critically ill patients) with citrate measurement available before and after the dialysis filter were reviewed. estimation of the liver clearance was performed using the picco lemon ® system (pulsion). in addition, sessions performed using ccf-ihd were reviewed. results: all the patients had liver disorders (post-liver transplantation period n = ; cirrhosis with child > a ). among the eighteen cafcit-ihd patients, fifteen ( %) and six ( %) received mechanical ventilation or vasopressive drugs, respectively. the median time of the dialysis session was h [ ] [ ] [ ] [ ] , with hourly ultrafiltration rate of ml (one premature termination not related to dysfunctional catheter). in all patients, ionized calcium (ica) decreased below . mmol/l after the filter, whereas post-filter calcium reinjection according to ionic dialysance led to a stable pre-filter (i.e. patient) ica. median citrate concentrations were all below . mmol/l after the filter (minimal concentration to obtain anticoagulation mmol/l) and all except one below the normal value (< µmol/l) before the filter. during all the sessions, ionized to total calcium ratio was below . and the strong ionized gap decreased. when available (n = ), no correlation could be identified between serum citrate concentration and liver clearance. last, in ccf-ihd sessions performed in critically ill patients, no premature termination occurred (median time of the sessions h) and post-filter ica also decreased below . mmol/l. no citrate accumulation could be identified in critically ill patients (even with liver disorders) and receiving extended dialysis sessions ( h or more) using calcium-free citrate containing-ihd. interestingly, we demonstrated that citrate is not required to obtain optimal regional anticoagulation (i.e. post-filter ica < . mmol/l), and a citrate-and calcium-free dialysate could be a safe alternative. compliance with ethics regulations: yes. rationale: ventilator induced diaphragmatic dysfunction is highly prevalent in adult critical care and associated with worse outcomes. specificities in pediatric respiratory physiology suggest that critically ill children may be at high risk of developing this complication, but no study has described the evolution of diaphragmatic function in critically ill children undergoing mechanical ventilation. this study aims to validate a method to quantify diaphragmatic function in mechanically ventilated children. in this prospective single-center observational study, children between week and years old intubated for elective ent surgery and without pre-existing neuromuscular disease or recent muscle paralysis were recruited. immediately after intubation, diaphragmatic function was evaluated using brief airway occlusion maneuvers during which airway pressure at the endotracheal tube (paw) and electrical activity of the diaphragm (eadi) were simultaneously measured for consecutive spontaneous breaths, while the endotracheal tube was occluded with a specific valve. occlusion maneuvers were repeated times. in order to account for central respiratory drive and sedation use, we recorded the neuromechanical efficiency ratio (nme, paw/eadi), in addition to the maximal inspiratory force (mif). in order to determine the optimal measure of nme during an occlusion, the variability over the three occlusion maneuvers of different variables (first breath, last breath, breath with maximal paw deflection, breath with maximal nme value, and median nme value) was assessed using coefficients of variation and repeatability coefficients. results: patients had a median age of . years (interquartile range . - . ), a median weight of kg ( - ), and were male ( %). the median evolution of paw, eadi, and nme ratio over the occluded breaths are represented on fig. . nme values corresponding to the last breath and the breath with maximal paw deflection were the least variable, with median coefficient of variation of % and % and repeatability coefficients of . and . , respectively. conclusion: brief airway occlusions can be used to assess diaphragmatic function in intubated children through both mif and nme ratio, and the latter should ideally be computed on the last breath or the breath with the largest pressure deflection to improve repeatability and decrease variation. compliance with ethics regulations: yes. epidemiology is poorly understood due to the rare use of validated diagnostic tools. the main objective of the study was to determine, by systematically calculating the wat- score, the incidence of ws in our surgical picu. the secondary objective was to analyze the risk factors, consequences and management modalities of ws. patients and methods: following institutional review board approval, we conducted a prospective monocentric study between july and january . all consecutive mechanically ventilated children admitted in our surgical picu with sedation/analgesia by continuous intra-venous (iv) benzodiazepines (bzd) and/or opioids for at least h were included. as soon as sedation was decreased and during h following their total discontinuation, wat- score was assessed twice a day. ws was defined by a wat- score > . the search for risk factors and consequences associated with ws was performed by univariate analysis (mann-whitney and chi test). ethical standards were satisfied and the lack of opposition from patients and their parents was systematically checked. results: the incidence of ws was % among the patients of our cohort including % of children admitted postoperatively and % after severe traumatic brain injury (tbi). significant results are reported in table . our results show that even for sedation time less than days, children could develop ws ( / patients). on the other hand, age, severity (pelod score), number of previous surgeries and severe tbi were not associated with ws. our study also demonstrated that cessation of sedation and prevention of ws was not uniform in our unit. the high incidence of withdrawal syndrome in our study, even in children sedated for less than days, and its consequences require thinking about prevention. we suggest a systematic monitoring of the occurrence of this adverse event using a validated score, from days of continuous iv sedation/analgesia. compliance with ethics regulations: yes. rationale: severe traumatic brain injury (tbi) is a major healthcare problem. amplitude and duration of intracranial hypertension is highly associated with patient outcome. the intracranial pressure (icp) is therefore one key parameter to monitor in the acute phase. when icp is monitored with an external ventricular drain, the pressure recorded by the monitor does not always correspond to the real icp, depending on the status (open/closed) of the -way tap. misleading values could therefore be sent to the patient medical record. our hypothesis is that a machine-learning algorithm will be able to identify automatically and in real time the reliable and non-reliable values of the icp signal. we retrospectively studied pediatric patients having an external ventricular drain between july and july , in a single pediatric intensive care unit. the icp signals were extracted from a high-frequency database ( hz) and pre-processed adequately. to train the algorithms, an annotated database was manually created with two classes: reliable icp vs. non-reliable icp (drain system opened to allow cerebrospinal fluid removal). eleven signal characteristics were compared between the two classes (mann-whitney test), and significantly differing variables were tested in the algorithms. we compared the performance of two machine-learning algorithms: the k-nearest neighbors (knn) and the support vector machine (svm). using -fold cross-validation method, % of the data was used to train the algorithms and % was used for testing. the best classifier was further validated by simulating a real-time icp analysis, using a s sliding-window approach with % overlap. the study was approved by the localresearch ethics committee. results: sixteen patients were included in the study. the training database created from patients, contained segments (of s duration) per class and per patient. eight signal variables were identified and kept to define the segments. the knn algorithm, with k = , led to the best performance, with a mean of % (mean ± sd: % ± . %). the knn was then visually validated on icp signals from the remaining two patients ( figure) . by simulating a real-time icp extraction, our algorithm was able to efficiently identify the reliable icp segments, and to display a mean value only for valid segments. university hospital picu (paris). all consecutive children ( month- years) admitted for acute encephalitis were included and diagnosis was confirmed using the consensus conference criteria's. data regarding clinical, biological and radiological presentations were collected as well as data on the therapeutics used and outcomes at discharge and at the last medical consultation. results: patients were included with a mean age of . years (range . to years old). infectious causes were identified in % (n = ), autoimmune causes in % (n = ) and acute demyelinating encephalomyelitis in % (n = ) of cases. etiology remained undetermined in % of cases (n = ). the most common pathogens were, in order of frequency, influenzae virus, mycoplasma pneumoniae and epstein-bar virus. the main clinical features were fever ( % n = ); epileptic seizures ( % n = ) and coma ( % n = ). regarding therapeutics, % of patients required mechanical ventilation and % of patients required hemodynamic support. % received corticosteroids, % intravenous immunoglobulins and % plasmatic exchanges. the use of these specific treatments was heterogeneous, especially in infectious and undetermined encephalitis, where respectively % and % received boluses of corticoids. the mean length of stay in picu was . days (range - days). the mortality rate was % and the overall rate of sequelae at discharge was % and % at distance, with % considered as severe (gose-ped score > ). the use of mechanical ventilation and young age at diagnosis were risk factors associated with poor prognosis at discharge. the etiology of acute encephalitis remains indeterminate in more than % cases with a clear predominance of infectious causes when an etiology is found. this is a severe pathology responsible for significant mortality and morbidity requiring long-term follow-up. compliance with ethics regulations: yes. rationale: preserving neurological outcome of children under extracorporeal membrane oxygenation (ecmo) remains challenging. acute brain injury (abi) is a frequent complication of ecmo that could be prevented by continuous neuromonitoring. cerebral near infrared spectroscopy (nirs) is routinely used for detecting cerebral complications of cardiac surgery. in adults and infants under prolonged ecmo, cerebral hypoxia is associated with poor neurological outcome. the aim of this study was to assess the value of an impaired cerebral oxygenation on mortality and occurrence of an abi in children under ecmo. patients and methods: children under years old were included in this observational retrospective monocentric study if they needed veno-venous (v-v) or veno-arterial (v-a) ecmo for respiratory and/ or circulatory failure and had concomittant nirs monitoring. cerebral desaturation was defined as a rsco value under % or under % from the baseline; cerebral hyperoxia was defined as a rsco value above %. proportion of time in cerebral desaturation and hyperoxia were recorded. neurological lesions were identified on imaging (mri or scan) by blinded radiologist and classified as major or minor. abi was defined as any hemorragic or ischemic lesion on cerebral imaging, including brain death. results: patients were included. ecmo duration was [ ; ] days. the mortality rate was ( . %), and the proportion of abi was ( %) including brain deaths, ( . %) major lesions, and ( . %) minor lesions. mean rsco was ± % in the right hemisphere, and ± % in the left hemisphere. there was no significant difference in cerebral hypoxia between survivors and non survivors, and between patients with and without an abi. cerebral hyperoxia was associated with a better survival (p = . in the right hemisphere, and p = . in the left hemisphere). in v-v ecmo and at the right conclusion: in our study, cerebral hypoxia was not associated with poor neurological outcome, but cerebral hyperoxia seems to be protective especially in v-v ecmo. this is the first study assessing the value of cerebral oxymetry in all age ranges pediatric ecmo. in this population, multimodal monitoring might be better than nirs alone to predict neurological impairment. further prospective studies are needed to assess first the feasibility, then the impact of such a monitoring. compliance with ethics regulations: yes. cerebral autoregulation impairment is associated with acute neurological events during pediatric extracorporeal membrane rationale: children supported by extracorporeal membrane oxygenation (ecmo) present a high risk of adverse neurological complications. as some animal studies have shown, cerebral autoregulation (ca) impairment after exposure to ecmo, may be a key factor. our main objective was to investigate the feasibility of ca continuous monitoring during ecmo treatment. the second objective was to analyze the relationship between ca impairment and neurological outcome. patients and methods: an observational prospective study including children treated by ecmo in centers was conducted. a correlation coefficient between the variations of regional cerebral oxygen saturation (rsco ) and the variations of mean arterial blood pressure(map) was calculated as an index of ca (cerebral oxygenation reactivity index, cox) during ecmo. a cox > . was considered as indicative for dysautoregulation. cox values were averaged inside mmhg-map bins, allowing determining optimal map (mapopt) and lower (lla) and upper (ula) limits of autoregulation in -h periods. neurological outcome was assessed by the onset of an acute neurologic event (ane) defined by occurrence of hemorrhagic or ischemic stroke and/ or clinical or electrical seizure and/or brain death during the ecmo treatment. rationale: myocardial ischemia reperfusion (ir) injury is the leading cause of perioperative morbi-mortality. protective effect of pharmacologic preconditioning such as anesthetic preconditioning (apc) with sevoflurane (sev) has been widely demonstrated in animal and human models. apc seems to protect myocardial cells from apoptosis, a programmed process of cell death tightly controlled by bcl- family proteins. however, the involved mechanisms in apc have yet to be characterized. we hypothesized that apc protects against myocardial apoptotic cell death by regulating bcl- anti-apoptotic members. to study the sev-induced apc mechanisms against myocardial ir, we used a validated in vitro model reproducing ir injury. rat cardiomyoblast cells h c were cultivated in . % o hypoxia in the presence of ischemia-mimicking medium. after min of ischemia, the reperfusion injuries are induced by replacing the culture medium with a krebs-henseleit normoxic medium for min. apc was performed by adding sev directly into the culture medium at an initial concentration of mm, prior to ischemia, for min. we then used another preconditioning agent, metformin (met), to explore the same signaling pathways. apoptotic cell death was measured by caspase activity assay and western blotting (expression of cleaved caspase ) under ir and apc conditions. results: our model faithfully reproduced the protective effect of apc which results in a significant decreased apoptosis under ir ( % reduction of the caspase enzymatic activity, correlated with a decrease of caspase cleavage). we showed that sev induces overexpression of the anti-apoptotic protein bcl-xl, which is responsible for the protective effect of apc. furthermore, these observations were confirmed in vivo in mouse heart lysates. we demonstrated that bcl-xl overexpression was due to the activation of the protein kinase akt. interestingly, we were able to show that preconditioning with met reproduces the protective effect of sev by inducing an akt-dependent bcl-xl overexpression. indeed, sev and met, which are both complex inhibitors of mitochondrial respiratory chain, seem to share a common reactive oxygenated species-dependent protective mechanism responsible for bcl-xl protein regulation. rationale: despite early endovascular treatment with successful recanalization, % of acute ischemic stroke (ais) patients experience a poor functional outcome after a large vessel occlusion. sepsis is frequent at the acute phase of stroke and is associated with poorer short and long term outcomes. we aimed to investigate the cerebral consequences of sepsis after recanalized ais and explore possible mechanisms involved. patients and methods: male c bl mice were randomly assigned to a x factorial plan to one of the following groups: ) a -minute middle cerebral artery (t-mcao) transient occlusion under inhaled general anesthesia, followed min after recanalization by intraperitoneal (i.p.) sepsis (lps, µg/g diluted in µl of nacl . %), (tmcao/ lps group); ) t-mcao followed by i.p. placebo ( µl of nacl . %) (tmcao/placebo group); ) sham operation (cervicotomy without carotid catheterization) followed by i.p. lps. (sham/lps group); ) sham operation followed by i.p. placebo, (sham/placebo group). in all groups, animals received subcutaneous fluid resuscitation ( µl nacl . %) immediately after the procedure and h later. twenty-four hours after recanalization, animals were scored for sepsis features and neurological deficit (on the modified neurological severity scale), (mnss) before sacrifice. the primary outcome measurement was a composite of death and hemorrhagic transformation at h. secondary outcome measurements included neurological deficit, sepsis features, neutrophil activation reflected by plasmatic myeloperoxydase (mpo) levels, stroke volume, and microglial activation in brain parenchyma (infarct core, perilesional area, controlateral hemisphere). results: t-mcao/lps animals had higher mnss ( . fold, p = . ) and sepsis ( fold, p = . ) scores at h with increased plasma mpo levels at h ( . fold, p < . ) and h ( . fold, p < . ), as well as, lower temperature ( . °c reduction, p = . ) and glycemia ( . g/l reduction, p = . ) as compared to tmcao/placebo animals. t-mcao/lps animals had a higher risk of unfavorable outcome at h ( -group comparison: p = . ; x analysis: t-mcao/lps, / − %vs. t-mcao/placebo / - %-, p < . ), whereas stroke volumes were not significantly different between groups. detailed results are presented in table . compared to t-mcao/placebo group, t-mcao/ lps animals had . fold increase (p = . ) in the mean number of microglial cells in the hemisphere controlateral to t-mcao, whereas no significant difference was observed in infarct core or peri-infarct parenchyma. conclusion: early sepsis after experimental ais worsens outcome and neurological deficit, without impacting stroke volume. early sepsisinduced systemic activation of neutrophils and increased microglial activation in the hemisphere contralateral to ischemia may have an important role on neurological outcomes observed in this setting. compliance with ethics regulations: yes. rationale: extracellular vesicles (evs) regulate diverse cellular and biological processes via facilitating intercellular cross-talk. several studies have suggested an association between lung injury and the generation of evs derived from platelets, neutrophils, monocytes, lymphocytes, red blood cells, endothelial cells, and epithelial cells. every year more than , patients require cardiac surgery with cardiopulmonary bypass (cpb). this cpb allows a substitution of the heart pump function and an oxygenation of the blood permitting a stop of the mechanical ventilation (mv). stopping mv during cpb is responsible for lung damage, leading to postoperative systemic inflammation while maintaining mv with positive expiratory pressure (peep) diminished the occurrence of atelectasis and the postoperative inflammatory response. in addition, this surgery is marked by immune dysfunction, leading to real immunosuppression of patients in postoperative care. a link between pulmonary injury and postoperative immunosuppression has been established, however, the mechanisms underlying this association are not fully known and evs may have a role in this post-operative immunosuppression. the purpose of this study is to investigate whether lung injury induced during cardiac surgery with cpb lead to the emergence of evs. the effect of mv during cpb on the production of these evs has also been studied. patients and methods: patients were prospectively divided into two groups: without mv during cpb and dead space mv with positive end-expiratory pressure during cpb. pao (arterial oxygen tension)/ fio (inspired oxygen fraction) ratio, biological markers of lung injury (cxcl , ccl , tnf-α, il- β, il- , rage, il- ) and blood cell count were collected before, h and days after surgery. the quantification of plasma evs was performed using turnable resistive pulse sensing and characterization of evs was performed using flow cytometry before, h and days after surgery. rationale: the benefit of prone positioning (pp) during moderate to severe acute respiratory distress syndrome (ards) may be related to its impact on the inflammatory response to ventilator-induced lung injuries. [ c]-pk is a positron emission tomography (pet) radiotracer that allows the non-invasive quantification of macrophages. we aimed to evaluate the effects of pp on [ c]-pk lung uptake in animals with experimental ards. patients and methods: experimental ards (by hydrochloric acid) was induced in pigs in supine position (sp), to obtain a pao / fio < mmhg. animals were under general anesthesia, neuromuscular blockade, and ventilated with a ml kg − tidal volume, and cmh o of positive end-expiratory pressure (peep). immediately after experimental ards, animals were randomized to be prone positioned, or to remain in sp. pet and computerized tomography (ct) were acquired h after randomization (h ). [ c]-pk uptake was measured on the whole lungs, and by dividing the lungs into regions or slices-of-interest (soi) along the ventro-dorsal axis, and was quantified by the standardized uptake value (suv), corrected for lung tissue density. results: pp was performed in animals, and sp in . after ards induction, pao /fio was [iqr, [ . - . ] in sp animals (p = . ). in pp animals, [ c]-pk suv was significantly lower in ventral soi, compared to sp, and significantly increased in dorsal soi ( fig. , *: p < . between groups in a given soi). in univariate analysis, [ c]-pk regional suv was positively associated with regional ct-measured peep-related increase in gas volume, and negatively with peep-related lung recruitment, but not with regional tidal volume. conclusion: during experimental ards, pp redistributed lung macrophage recruitment estimated by [ c]-pk uptake from ventral lung regions to dorsal regions, without affecting global macrophage influx. the intensity of macrophage recruitment was associated with peep-related lung inflation. compliance with ethics regulations: yes. rationale: acute respiratory distress syndrome (ards) is a pleiomorphic disease characterized by a severe respiratory failure associated with an increased mortality. nowadays, predicting clinical outcome of patients suffering from ards remains difficult. therefore, identifying new biomarkers to predict patient outcome, to evaluate response to therapy and to identify new potential pathways of interest are highly needed. exosomes are extracellular vesicles involved in cell-cell communication by transferring micrornas (mirnas) from donor to recipient cells. thus, exosomal mirnas can significantly affect biological pathways within recipient cells resulting in alterations of cellular function and the development of a pathological state. as biomarkers are highly needed in the particular field of ards, we realized a monocentric and prospective study to identify a new potential biomarker of interest. therefore, a prospective plasma sampling at the diagnosis of moderate to severe ards according to the definition of "berlin" has been performed. we analysed mirna content of exosomes from plasma ards patients compared to healthy subjects (hs) in order to identify new potential predictive biomarkers in ards. during one-year period, patients hospitalized in the icu of chu sart tilman suffering from infectious moderate-to-severe ards have been included. the ethical committee review boards of the hospital approved the research protocol (b , ref: / ), and informed consents were obtained. exosomes were isolated from plasma samples of ards patients and hs with standard ultracentrifugation protocol. exosomal mirna content was analyzed using small rna sequencing method, and diseases/biological processes associated to altered mirs were determined by bioinformatic analysis. results: for the first time, exosomal mirna expression modifications were studied in patients with moderate-to-severe infectious ards. we identified a new signature statistically significant composed of three up-regulated mirnas (mir- , mir- a and mir- ) and one downregulated (mir-let- b). conclusion: we identified potential biomarkers for ards from plasma exosomes. our findings may thus lead to predict ards outcome but also a better understanding about the roles of these mirs in the pathogenesis of ards and thus open new avenues for therapeutic approaches. in particular, exploit and develop the pro-fibrotic pathway induced by down-expression of mir-let- b. but also confirm in the future the current interest about mir- in its ability to restore pulmonary integrity after trauma. compliance with ethics regulations: yes. rationale: diabetic ketoacidosis (dka) is a life-threatening emergency. microvascular hyporeactivity was reported in these patients and was completely reversibly when ph was corrected with treatment: aggressive rehydration, electrolyte replacement and insulin therapy ( ) . red blood cell (rbc), a component of the microcirculation, showed alterations oftheir shape in diabetic patients ( ) but no data were available concerning the time course of the rbc deformability during treatment for dka. we aimed to assess the rbc deformability during dka treatment in icu patients. patients and methods: after approval by the ethics committee, rbcs deformability was assessed, in all icu patients admitted for dka and without infection, by ektacytometry technique (laser-assisted optical rotational red cell analyzer-lorrca): at icu admission, + h, + h and at the end of the icu stay ( - h). elongation index (ei) was defined as (l − w)/(l + w), where l is the length and w is the width. at °c, ei values were determined in the function of shear stress (ss) in a range of . - pa, based upon the laser diffraction pattern changes. a higher ei indicates greater rbc deformation. rbc deformability from patients with dka was compared at icu admission to healthy volunteers (v) and to diabetic patients followed in consultation (d). we also studied the evolution of deformability during treatment. results: icu dka patients compared to d and v were studied. as expected, glycemia and glycated hemoglobin were significantly higher in dka compared to d (respectively: glycemia: ( - ) vs ( - ) mg/dl and . % ( . - . ) vs . ( . - . ); all p < . ). dka patients received ( - ) ml of fluids and . ui/ kg bw ( . - . ) of insulin during their first h of icu stay. rbcs deformability from dka patients was significantly more altered at icu admission compared to others groups ( fig. ) and these alterations persists despite treatment. no correlations were observed between these alterations and quantity of fluids or insulin received, glycemia, glycated hemoglobin, ph, natremia, age or length of diabetes history. conclusion: in contrast of reversible microvascular hyporeactivity, rbc deformability from dka patients was already altered at icu admission and remains altered despite treatment. these alterations could contribute to the blood flow abnormalities observed in these patients. compliance with ethics regulations: yes. rationale: sepsis remains the first cause of acute circulatory failure in the emergency department (ed). standardized fluid resuscitation may not be adapted in certain patients, especially those with early sepsisinduced cardiac dysfunction in whom excessive fluid administration could be deleterious. information on early hemodynamic profile of septic patients in the ed are scarce. accordingly, we aimed at describing hemodynamic profiles encountered in septic patients assessed shortly after their ed admission using focused echocardiography. patients and methods: we prospectively enrolled adult patients with sepsis (qsofa score ≥ ) from january to july in the ed (nct ). focused echocardiography were performed by emergency physicians previously trained to ecmu level. each patient was evaluated according to a standardized protocol based on a limited number of simple binary clinical questions. investigators interpreted on-line the echocardiographic examination, determined the hemodynamic profile based on simple yet robust criteria (hypovolemia, left ventricular [lv] or right ventricular [rv] failure, vasoplegia with hyperdynamic state, tamponade, severe mitral or aortic regurgitation, or apparently normal profile), and recorded any substantial change in planned therapeutic management (surviving sepsis campaign ). data were digitally stored and validated off-line by an expert in critical care echocardiography. results: focused echocardiography were performed in patients (mean age: ± years; men: %; source of infection: pulmonary %, urinary %, abdominal %) after a median fluid loading of ml (iqr: - ml). according to sepsis- definition, patients had sepsis and sustained septic shock. mean sofa score was . ± . (hemodynamic failure %, respiratory failure %, renal failure %), mean lactate reached . ± . mmol/l, icu admission involved % of patients and overall -day mortality reached %. hemodynamic profile was hypovolemia in patients ( %), vasoplegia in patients ( %), cardiac failure in patients ( %) (lv failure: n = ; rv failure: n = ) and without relevant hemodynamic abnormality in patients ( %). ongoing therapy was altered based on early echocardiographic assessment in % of cases. mortality rate was not significantly different between groups (p = . ). conclusion: although hypovolemia was predominantly identified in patients presenting to the ed with sepsis during hemodynamic assessment, early ventricular dysfunction involved one-quarter of patients. these results suggest that early focused echocardiographic assessment promises to help the front-line physician tailoring the therapeutic management of septic patients in ed, especially regarding fluid resuscitation. compliance with ethics regulations: yes. right ventricular failure in septic shock characterization, incidence and impact on fluid-responsiveness guillaume geri , amélie prigent , xavier repessé , marine goudelin , gwenael prat , bruno evrard , cyril charron , philippe vignon , antoine vieillard-baron ambroise paré hospital, boulogne-billancourt, france; ambroise paré hospital, medical icu, aphp, boulogne-billancourt, france; chu limoges, limoges, france; chu brest, brest, france correspondence: guillaume geri (guillaume.geri@aphp.fr) ann. intensive care , (suppl ):f- rationale: right ventricular (rv) failure was defined by rv dilatation with systemic congestion. tricuspid annular plane systolic excursion (tapse) could be of limited value. we report the incidence of rv failure in patients with septic shock, its potential impact on the response to fluids, as well as tapse values. patients and methods: ancillary study of the hemopred prospective multicenter study including patients under mechanical ventilation with circulatory failure. with septic shock were analyzed. patients were classified in groups based on central venous pressure (cvp) and rv size (rv/lv end-diastolic area, eda). in group , patients had no rv dilatation (rv/lveda < . ). in group , patients had rv dilatation (rv/ lveda ≥ . ) with a cvp < mmhg (no venous congestion). rv failure was defined in group by rv dilatation and a cvp ≥ mmhg. passive leg raising (plr) was performed. results: % of patients were in group , % in group and % in group . in group and , rv/lv eda was higher than in group , . [ . ; . ] versus . [ . ; . ]. cvp was [ ; . ] mmhg in group . a correlation between rv size and cvp was only observed in group . higher rv size was associated with a lower response to plr (figure) . a large overlap of tapse values was observed between the groups. . % of patients with rv failure had an abnormal tapse. conclusion: rv failure is frequent in septic shock and alters fluid responsiveness. tapse was not accurate enough to diagnose rv failure. compliance with ethics regulations: yes. rationale: weaning-induced pulmonary oedema (wipo) is a leading cause of weaning failure in high-risk patients (heart failure, copd, obesity). we hypothesized that hypervolemia associated with positive fluid balance facilitates wipo in high-risk patients. patients and methods: in this prospective, observational, singlecenter study, patients with copd and/or heart failure with reduced ejection fraction (< %) were studied. exclusion criteria were nonsinus rhythm, severe mitral valve disease and inability to obtain adequate echocardiographic views. echocardiography was performed immediately before and during spontaneous breathing trial (sbt, -min t-tube). patients who failed sbt were treated according to echocardiographic results before undergoing a second sbt. fluid balance and body weight were collected at each sbt. shows interesting performance to predict fluid responsiveness in spontaneously breathing patients. nevertheless, measurement sites of inferior vena cava (ivc) diameters remain controversial for that purpose. the aim of the study was to test the accuracy of different measurement sites of civc to predict fluid responsiveness in spontaneously breathingpatients. this study is a post hoc analysis of two prospective cohorts. we included spontaneously breathing patients without mechanical ventilation presenting with sepsis-related acute circulatory failure and considered for volume expansion (ve). we assessed hemodynamic status at baseline and after a fluid challenge (fc) induced by a min-infusion of ml-gelatin %. the ivc diameters were measured off-line with ultrasonography using the bi-dimensional mode on a subcostal long-axis view. the civc was calculated as [ (expiratory-inspiratory)/expiratory] diameters during standardized (civc-st) and unstandardized breathing (civc-ns) conditions. breathing standardization consisted of a deep inspiration with concomitant control of buccal pressures and passive exhalation. patients were referred to be responders to fc (i.e. fluid responsive) when the stroke volume increased by ≥ %. results: among the patients included in the study, ( %) were responders to fc. the accuracy of civc-st and civc-ns before fc to predict fluid responsiveness differed significantly by measurement sites (interaction p value < . and < . , respectively). measuring ivc diameters cm from the junction of the ivc and the right atrium provided the best accuracy to predict fluid responsiveness ( fig. ). at cm caudal to the right atrium, civc-st was significantly better than civcns to predict fluid responsiveness: area under roc curve . ( % ci . - . ) versus . ( % ci . - . ), p < . . at cm, a civcst ≥ % and a civc-ns ≥ % predicted fluid responsiveness with sensitivity of % and %, and specificity of % and %, respectively. conclusion: accuracy of civc to predict fluid responsiveness in spontaneously breathing patients depends on both measurement sites of ivc diameters and breathing conditions. measuring ivc diameters during a standardized inspiration maneuver at cm caudal to the right atrium is the most relevant mean to optimize civc performance to guide ve. compliance with ethics regulations: yes. rationale: intermittent hemodialysis (ihd) is increasingly used in patients admitted to intensive care unit (icu) with acute kidney injury (aki) requiring renal replacement therapy (rrt). however, this technique is associated with nearly % of episodes of perdialytic hemodynamic instability (hi), a common cause of increased morbidity and mortality. at the same time, trans-thoracic echocardiography (tte) has become widely used in intensive care units and is now one of the hemodynamic monitoring methods used daily in the icu setting. patients and methods: search for one or more pre-dialysis tte criteria predictive of perdialytic hi, defined by a systolic blood pressure (sbp) lesser than mmhg or a suddain decrease in sbp of more than mmhg. prospective, observational study of standard care in a medical icu. collection of demographic, clinical and pre-dialysis echocardiographic data from included patients. results: twenty-five patients with a total of sessions of ihd between november and november were included in the study. tte was performed for each patient before each ihd session. hi occurred in hemodialysis sessions. in univariate analysis, the existence of prior heart disease ( % vs %, p = . ), a greater diameter of the left atrium ( . vs . cm, p = . ), a lower cardiac output ( . vs . l/min, p = . ), a right dysfunction assessed by lowered tapse and s-wave ( vs mm, p < . and . vs . cm/s, p = . , respectively) and an increase in paps ( vs mmhg, p = . ) were significantly associated with the occurrence of perdialytic hi (fig. rationale: several transthoracic echocardiography (tte) parameters of left (lv) and right ventricular (rv) systolic function are available. we compared the ability of these different parameters to track changes in lv or rv systolic function and to detect lv or rv systolic dysfunction in critically-ill patients. in patients ( mechanically ventilated and with atrial fibrillation), tte examinations were performed before and after i) infusion of -ml of saline (n = ), ii) changes in norepinephrine (n = ), iii) or in dobutamine (n = ) dosage. for the lv systolic function, we compared the mitral annular plane systolic excursion (mapse), the systolic (s') peak velocity of the lateral mitral annulus and the global longitudinal strain (glslv) to the lv ejection fraction (lvef), considered as the gold standard. for the rv systolic function, we compared the tricuspid annular plane systolic excursion (tapse), the systolic peak (s) velocity of the tricuspid annulus and the global longitudinal strain (glsrv) to the rv fractional area change (fac), considered as the gold standard. results: after pooling all values, lvef ( ± % at baseline) was better correlated to glslv (r = . ) than to mapse (r = . ) and s' wave (r = . ) (each p < . ). the concordance rate between changes (in %) in lvef and in the other parameters of lv systolic function was % for glslv, % for mapse and % for s' wave. both mapse and s' wave could not reliably detect moderate ( % ≤ lvef ≤ %) or severe (lvef < %) lv dysfunction. conversely, a glslv > − % predicted moderate lv dysfunction with a sensitivity of % ( % ic: - %) and a specificity of % ( % ic: - %) and a glslv > − . % predicted severe lv dysfunction with a sensitivity of % ( % ic: - %) and a specificity of % ( % ic: - %). after pooling all values, fac ( ± % at baseline) was better correlated to glsrv (r = . ) than to tapse (r = . ) and s wave (r = . ) (each p < . ). the concordance rate between changes (in %) in fac and in the other parameters of rv systolic function was % for glsrv, % for tapse and % for s wave.both tapse and s wave could detect rv dysfunction (fac ≤ %) with moderate reliability only. conversely, a glsrv > − % detected rv dysfunction with a sensitivity of % ( % ic: - %) and a specificity of % ( % ic: - %). in critically-ill patients, glslv and glsrv seem to be the best tte parameters of lv and rv systolic function. enrolments are still ongoing, which may allow further analysis. compliance with ethics regulations: yes. rationale: passive leg raising (plr), pulse pressure variation (ppv), and the -second end-expiratory occlusion test (eexpo) are frequently used to assess preload responsiveness. however, there are conditions in which they are not valid or feasible, which may preclude their applicability in the daily clinical practice. the aim of this study was to estimate the prevalence of such conditions in critically ill patients with acute circulatory failure. between january and april , all patients of a -bed medical icu were daily screened and those with acute circulatory failure, defined by norepinephrine infusion or fluid therapy > l during the previous h, were included. in each of them, we screened the criteria of validity/feasibility of ppv, plr and eexpo. results: eighty-four patients ( % with septic shock, % with cardiogenic shock, % with hypovolemic shock, % with non-septic vasoplegic shock) were enrolled in the study. among them, norepinephrine infusion was ongoing at the time of enrolment in % of the patients whilst % were under mechanical ventilation, and % with acute respiratory distress syndrome. plr was not applicable in % of cases. this was mainly due to venous compression stocking ( % of cases), intra-abdominal hypertension ( % of cases), and either an absence of cardiac output monitoring or impossibility to perform echocardiography ( % of cases). among the intubated patients, ppv was applicable in % of cases, including cases with high ppv under conditions generating false negatives (low tidal volume or lung compliance) or low ppv values under conditions generating false positives (spontaneous breathing, cardiac arrythmias). however, ppv was not interpretable in % of cases. this was mainly due to low tidal volume ventilation ( % of cases), spontaneous breathing activity ( % of cases), while the remaining non-interpretable cases ( %) had more than one reason. in the intubated patients, eexpo was not applicable in % of cases. this was due to impossibility for patients to sustain a -s hold of mechanical ventilation in % of cases, and either an absence of cardiac output monitoring or the impossibility to perform echocardiography in % of cases. plr and eexpo were both valid and feasible in % of the patients, and the three tests were all feasible in only % of patients. rationale: comorbid association between chronic respiratory diseases and sleep apnea syndrome (sas) revealed frequent with systematic search in icu following icu stay. this association carries prognosis impact depending whether specific treatment is implemented or not. nosas and stop bang scores are proposed for screening of sas in general population. the aim of the present study is to report the prevalence of sas in icu patients admitted for hypercapnic respiratory failure and compare association of nosas and stop bang score with sas severity. the study was conducted between january and september . patients consecutively admitted in the icu for hypercapnic respiratory failure had calculation of a no sas and stop bang scores at admission. in survivors nocturnal polygraphic records was performed to weeks following icu discharge. the association between the number of apnea-hypopnea episodes, bmi, and clinical variables suggestive of sas, was tested by poisson regression model. results: during the study-period, patients (mean age: ± years, ph . ± . , paco ± ) were admitted for hypercapnic respiratory failure. non invasive ventilation was used in % and death occurred in six patients. polygraphic records were performed in ( lost to follow-up) mean apnea-hypopnea index was ± with a minimum of and a maximum of . poisson logistic regression showed that no sas (p = . ) but not stop bang (p = . ) was associated with the level of apnea-hypopnea index. rationale: patients with severe acute exacerbations of chronic obstructive pulmonary disease (copd) may benefit from high-flow nasal oxygen regarding its physiological effects and good tolerance. bronchodilator vibrating mesh nebulization through high-flow nasal oxygen circuit has been described to induce similar effect to standard facial mask jet nebulization in stable copd patients. we aim to evaluate whether vibrating mesh nebulization of salbutamol through highflow nasal oxygen circuit is efficient in unstable patients with copd. patients and methods: we conducted a monocenter non-randomized physiological prospective cross-over study, between january and september , including icu patients with severe acute exacerbation of copd and respiratory acidosis treated by salbutamol nebulization. spirometry and airway resistances records were performed after a -h wash-out period without bronchodilator, before and after vibrating mesh nebulization of mg salbutamol through high-flow nasal oxygen circuit. the primary endpoint was forced expiratory volume in s after salbutamol nebulization. secondary endpoints included other spirometry parameters, clinical parameters, dyspnea assessed by a borg scale. results: fourteen consecutive patients were included, forced expiratory volume in s increased significantly after salbutamol nebulization through high-flow nasal oxygen ( ± ml, p = . ), as well as forced vital capacity ( ml ± , p = . ). airway resistances were not significantly changed after nebulization (− . ± . , p = . ) as well as peak expiratory flow (+ ml ± , p = . ). no difference was observed on borg scale (p = . ) and respiratory rate (p = . ) after salbutamol nebulization, while heart rate increased significantly (p = . ). discussion: salbutamol nebulization using vibrating mesh nebuliser placed on high-flow nasal oxygen circuit induces a significant but moderate bronchodilation in patients with severe acute exacerbation of copd. moreover, improvement of forced vital capacity after salbutamol nebulization suggests a reduction of dynamic hyperinflation. conclusion: salbutamol vibrating mesh nebulization through highflow nasal oxygen circuit increases significantly forced expiratory volume in s. compliance with ethics regulations: yes. t-piece versus sub-therapeutic pressure support for weaning from invasive mechanical ventilation in patients with chronic obstructive pulmonary disease: a comparative prospective study amira jamoussi, fatma jarraya, samia ayed, takoua merhabene, jalila ben khelil, mohamed besbes abderrahmen mami hospital, tunis, tunisia correspondence: amira jamoussi (dr.amira.jamoussi@gmail.com) ann. intensive care , (suppl ):f- rationale: the best weaning strategy for patients with chronic obstructive pulmonary disease (copd) remains unknown. the spontaneous breathing trial (sbt) represents a crucial step of weaning, but the choice between the t-piece (sv-tube) or the sub-therapeutic setting of the level of pressure support without positive expiratory pressure (psv) is still a matter of debate. we aimed to compare the success of extubation between two groups of copd patients according to the sbt type (vs-tube vs psv). patients and methods: it was a prospective and comparative study, from april to march , at the abderrahmen mami hospital's intensive care unit (icu). copd patients who underwent invasive mechanical ventilation (mv) for at least h and met the criteria for weaning were included and randomized to sv-tube or psv. a multivariate analysis was performed to determine the association between the sbt modality and the success of extubation (no re-intubation during the h following extubation). results: during the two years' study, patients were included. the mean age was ± years, the sex-ratio was . . weaning process was simple in patients ( %), difficult in patients ( %) and prolonged in patients ( %). fifteen and patients were respectively randomized to the sv-tube and psv groups. the mean duration of mv before randomization was comparable between the groups (sv-tube . ± . days vs psv . ± . days, p = . ). mean weaning time (days) was . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] for the sv-tube group and . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] for the psv group. the mean total mv duration (days) was higher in the sv-tube group than in the psv group ( . vs . , p = . ). the number of re-intubated patients within h following extubation was higher in the psv group ( / vs / , p = . ) as well as the overall reintubation rate ( . % vs %, p = . ). in multivariate analysis, the sbt's trial was independently associated to the success of extubation (or = . , ic [ . - . ], p = . ) in favor of sv-tube' modality. the median length of stay in intensive care was days [ ; ]. the mortality was higher in the psv group ( / vs / , p = . ). extubation failure was a factor associated with mortality (or = . , ci [ . , . ], p = . ). conclusion: ventilation weaning was easy in % of intubated copd patients. sv-tube as sbt modality was associated to success of extubation in patients with copd. mortality in intensive care was significantly higher in re-intubated patients. compliance with ethics regulations: yes. rationale: non-invasive ventilation has become the mainstay in hypercapnic respiratory failure. delaying intubation and invasive ventilation is associated with a worse outcome in these patients. although a predictive score of niv failure has been validated for hypoxemic respiratory failure no such score exists in hypercapnic respiratory failure. the aim of our study is to compare the performance of two scores in the predictive niv failure hypercapnic respiratory failure. patients and methods: consecutive patients admitted between january and july for hypercapnic respiratory failure, were included. hacor score and rox score were calculated in each patient at admission. in patients ventilated non-invasively, the outcome (niv success or failure) was noted. the area under curve (auc) and operative characteristics were computed for both scores. results: during the study-period, out of patients admitted for hypercapnic respiratory failure received niv as the primary ventilatory mode. these patients were mainly men ( / ), had a mean age of . ± years and had the following pulmonary disease: copd exacerbation . %, obesity-hypoventilation syndrome . %, bronchiectasis . %, and other diseases: . %. niv failure occurred in patients ( . %) and icu mortality in . %. mean hacor score and rox score were . ± . and . ± , respectively. the auc under roc was higher for hacor than rox ( . and . respectively) ( fig. ). the hacor score (cut-off ) had a sensitivity of . and specificity of . . conclusion: hacor score seems more accurate in predicting niv failure in hypercapnic respiratory failure. further prospective validation is needed. compliance with ethics regulations: na. rationale: published data on outcomes in respiratory weaning centers are limited and seem to depend on the organisation of healthcare systems and patient case-mix. the weaning center of our university hospital (post intensive care rehabilitation unit) admits for weaning and rehabilitation patients from medical and surgical intensive care units without severe neurological pathologies. the aim of this study was to describe patient's characteristics and outcome (weaning outcomes and survival) and to compare in subgroups according to the initial medical, surgical or cardiac surgical context. patients and methods: we conducted a monocentric retrospective observational study between / / and / / . «successful outcome» was defined by the association of survival and weaning from invasive ventilation. factors associated with evolution were investigated by uni-and multivariate analysis. survival after discharge was analysed according to the initial context and according to the type of ventilation at discharge. results: among patients included, ( . %) had a successful outcome with high use of non-invasive ventilation (niv) ( %). respiratory history (p = . ), female gender (p < . ), igs score at admission to the srpr (p = . ) and non-cardiac surgical setting (p < . ) were associated with an adverse course. the -month survival rate was % in discharged patients. the outcome was not different in the tree subgroups. niv rate at discharge was high in the subgroup of cardiac surgery patients. a multidisciplinary and personalised approach by a specialized weaning unit can provide a successful service model for patients who require liberation from prolonged invasive mechanical ventilation. compliance with ethics regulations: yes. rationale: high-dose insulin euglycemic therapy (hiet) is recommended as first line therapy for calcium channel blockers (ccbs) poisoning because of its inotropic effect. our first objective was to study its hemodynamic impact. we performed a retrospective cohort study of all consecutive patients admitted for ccbs poisoning treated with hiet, in one icu at the university hospital of lille between january and july . the hemodynamic impact was studied through mean arterial pressure (map), vasoactive-inotropic score (vis) and map/vis ratio during the h following hiet initiation. metabolic parameters were also collected. results: patients admitted for ccbs poisoning. patients treated with hiet in icu ( patients without circulatory shock, patients with shock after hiet and patients with shock at baseline before hiet). among shocked patients at baseline (n = ), no hemodynamic improvement was found except an increased map/vis ratio at h (p < . ). on the contrary, an initial worsening of vis ( [ rationale: ketamine is used in the induction and maintenance of general anesthesia. recently, there were concerns regarding its liver toxicity. we conducted a study to investigate the link between ketamine use and liver dysfunction (ld) in intensive care unit (icu) patients. patients and methods: data were extracted from the [anonymized] study, a randomized controlled trial designed to evaluate the effect of cisatracurium on -day mortality rate in moderate and severe acute respiratory distress syndrome (ards) patients. the main endpoint was the occurrence of a ld defined as a total serum bilirubin superior or equal to micromol/l. a matched case-control cohort was created: cases, receiving at least day of continuous ketamine infusion, were paired for with controls according to treatment with cisatracurium, hepatic and cardiovascular sofa sub-score, total serum bilirubin level at the time of inclusion, age, sex, ards from septic origin, shock anytime after inclusion. an analysis was also made on the whole cohort comparing the patients receiving at least day of continuous ketamine infusion to all patients who did not fulfill this criterion. results: cases were identified and matched to controls. in the ketamine group, the median ketamine duration was ( - ) days, and median total cumulative dose . ( . - . ) g. the occurrence of ld was higher in the ketamine group than in the matched control group ( . % versus . %, p = . , fig. ). the hazard ratio (hr) for ld in the ketamine group was . ( % ci . - . , p = . ). there was an increased risk of ld of . % per day of exposure to ketamine (hr . , % ci . - . p = . ) and of . % per gram of ketamine infused (hr . , % ci . - . , p = . ), with a risk starting to be statistically significant after days and gr. in multivariate analysis on the whole cohort, ketamine exposure (hr . , % ci . - . , p = . ), cumulative dose in gram (hr: . , % ic: . - . , p = . ) and ketamine exposure in days (hr: . , % ic: . - . , p < . ) remained independent risk factors for ld occurrence. conclusion: ketamine use in critically ill patients treated for ards is associated to a higher risk of liver dysfunction, assessed by total serum bilirubin. this risk is dose-dependent and increases with duration of treatment. the prescription of high doses or prolonged treatment with ketamine should probably be avoided in critically ill patients. compliance with ethics regulations: yes. rationale: ciguatera is one of the most common cases of marine poisoning associated with fish consumption in the world. the incidence of this intoxication is largely unreported. in martinique, the incidence of this intoxication seems constantly increasing. during the last years, numerous cases of large collective poisonings have been reported in martinique, especially during summer. the spectrum of clinical manifestations is large including gastrointestinal, neurological andcardiovascular symptoms. ciguatoxin, the toxin responsible for ciguatera fish poisoning is considered as a sodium channel agonist with cholinergic and adrenergic activity. it is rarely fatal and management of poisoned patients is essentially based on supportive care. the objective of this study was to describe the clinical characteristics and complications of ciguatera poisoning in martinique, focusing on the cardiovascular ones. observational, retrospective, single-center study covering six-year period from october to september , including all patients admitted to the emergency department of the university hospital of martinique (chu), and all patients who were declared to the regional health agency (ars) for ciguatera intoxication. results: one hundred and forty-nine patients ( ) who were ciguatera-affected were included. the incidence rate found was to be . cases per . patient-years in martinique over the period. about % of patients had gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain; % neurological disorders and % cardiovascular symptoms including, bradycardia, hypotension and interventricular block. ingestion of carangue fish was related to a major risk of chronic signs. conclusion: the incidence of ciguatera in martinique is increasing, with . cases/ . patient-years. the clinical presentation is defined mainly by digestive signs, followed by peripheral neurological disorders and cardiovascular symptoms. ciguatera fish poisoning in martinique presents similar clinical presentation to that of the other caribbean islands. there is no specific treatment. acute ciguatera poisoning is responsible for significant cardiovascular complications. physicians should be aware of the potential cardiovascular risk of ciguatera poisoning. compliance with ethics regulations: yes. rationale: pesticides have represented the most incriminated products in severe acute poisonings, in the developing countries, due to the availability of these products. organophosphate poisoning accounts for million poisonings/year worldwide. organophosphate (op) pesticides are used mainly as insecticides in agriculture. the moroccan anti-poison and pharmacovigilance centrer shows that op poisoning are responsible for % of all poisonings combined. the aim of our study: epidemiological, clinical, management and prognostic factors. patients and methods: a retrospective study was conducted on patients with op poisoning admitted to our nine-bed medical intensive care unit between january and december . inclusion criteria were: all patients over years of age and the exlusion criteria were: pesticide poisoning other than op, alcohol poisoning, drug poisoning, scorpionic poisoning and snake bites. statistical analysis was performed with spss software. results: forty patients were admitted for acute op poisoning. in morocco, organophosphores are available over-the-counter in several forms: rodentocides, malathion, cockroach trap, baygon insecticide ( fig. ). the average age was years with a female prévalence of . %. the intoxications were mostly intentional ( %). the symptomatology was determined by the three syndromes: central syndrome in %, muscarinic syndrome in %, nicotinic syndrome in %. rhythm disorders in %, and cardiovascular collapse in %. the symptomatic treatment was applied to all patients, antidotic treatment was administered in % of patients. the average length of hospitalization was days. conclusion: acute op poisoning is a real public health problem. its associated symptomatic treatment (respiratory and neurological resuscitation) and antidotic treatment. the mortality remains high in our context, therefore, we must attach great importance to the prevention. compliance with ethics regulations: yes. ( ). over an -month period, health officials in guadeloupe and martinique reported more than . such cases. assault of these brown algae represents not only an environmental and economic disaster, but also a threat for human health. after h on seashore, large amounts of toxic gas are produced by matter decomposition, including hydrogen sulfide (h s) and ammoniac (nh ). the acute effects on humans after exposure to high concentrations of h s are well described and of increasing severity with concentration, leading to potentially fatal hypoxic pulmonary, neurological and cardiovascular injuries (table ) ; however, the association of long-term exposure to sargassum and health events is unknown. although less documented, long term exposures may result in conjunctiva and upper airways irritation, headaches, vestibular syndrome, memory loss, and modification of learning abilities. in the absence of any available antidote, management of h s intoxication relies on supportive care and prevention using individual protection. the objective of this study was to evaluate the clinical characteristics and consequences of long-term exposure to sargassum among the local population. we conducted a prospective observational cohort study including all patients admitted to the emergency department at the university hospital of martinique from march to december due to exposure to sargassum. patients were managed according to the protocol established by the research group on sargassum in martinique. we assessed the patients exposure to sargassum and air pollutants using monitor located near of the patient's residence. demographics and clinical data (including cardiovascular, neurological and respiratory events) were collected. data are presented as mean ± sd or %.comparisons were performed using univariate analysis. results: in months, patients were included (age: ± years, m/ w, past history: hypertension (n = ), diabetes (n = ), asthma ( ). patients arrived with referral letter from their general practitioner ( %) and presented headaches ( %), developed gastrointestinal disturbances ( %), dizziness ( %), skin lesions ( %), cough ( %) and conjunctivitis ( %). not all patients were clinically symptomatic. in the patients presented in june ( %), symptoms more frequently occurred in the workplace or at home (p < . ). initial lung function tests were normal ( %). three patients were admitted in intensive care unit. conclusion: our study indicates that the magnitude of health effects following long-term exposure to sargassum may be larger than previously recognized. efforts to limit long-term exposure are mandatory. compliance with ethics regulations: yes. rationale: liver consequences of out-of-hospital cardiac arrest (ohca) have been poorly studied. the aim of this study was to describe the characteristics of ohca-induced acute liver dysfunction and its association with outcomes. we analyzed all consecutive ohca patients admitted to two academic centers between and . patients treated with vitamin k antagonist were not included. acute hepatocellular insufficiency (ahi), liver failure (lf) and hypoxic hepatitis (hh) were defined as a prothrombin (pt) ratio < %, a hepatic sofa sub-score > and an increase in transaminases > times the normal values, respectively. indocyanine green (icg) clearance was used as the reference measure of liver function in a subset of patients. multivariate logistic regression was used to identify potential risk factors for day mortality. rationale: neuron-specific-enolase (nse) is commonly used as a biomarker reflecting the extent of brain injury in different settings. in post-cardiac arrest patients, previous clinical studies reported that an increase in nse was predictive of a poor outcome but did not specifically focused on neurological outcome. in this prospective study, we aimed to determine the nse performance for prediction of severe brain damage in post-cardiac arrest patients. patients and methods: all consecutive patients admitted in our icu after cardiac arrest between january and february that were still comatose at h and had at least one measurement of serum nse were included. blood samples for nse measurement were serially collected at (h ) and h (h ) after cardiac arrest and serum nse levels were measured within h. we used the following criteria for the definition of severe brain damage (primary endpoint): cerebral performance categories (cpc) or level at discharge, brain death or withdrawal of life-sustaining treatments (wlst) based on neurological status. we also assessed the predictive value of serum nse using allcause mortality as a secondary endpoint. results: during the study period, patients were available for the analysis. they were mostly male ( . %), with an age of . years. among these patients, ( . %) had a good neurologic outcome (cpc - ) and patients were classified as having a severe brain damage ( wlst based on neurological status, brain deaths and survivors with . in univariate analysis, patients with severe brain damage less frequently received bystander cpr, had longer duration of no-flow, less initial shockable rhythm, more post-resuscitation shock and higher nse values: mean at h were . versus . ; and . versus . at h (p < . ). nse levels at h and h were strong predictors of severe brain damage (auc of . and . respectively, figure ) and also predicted all-cause mortality (auc of . and . respectively). to predict severe brain damage with % specificity, best nse cutoff values at h and h were . and . µg/l, with a sensitivity of . and . % respectively. conclusion: a high serum nse measured at h and h after cardiac arrest accurately predicted severe brain damage with a high specificity. our results support the use of nse for neuroprognostication after cardiac arrest, in combination with other predictors. compliance with ethics regulations: yes. rationale: the psychological care of patients, their relatives and of healthcare workers is a major issue in the intensive care unit (icu). psychologists may provide emotional support during trying times. the intervention of a psychologist may alleviate long term mental health issues such as post-traumatic stress disorder. the main objective of our study was to describe the availability of psychologists in french-speaking icus. patients and methods: internet survey conducted between march and may using surveymonkey (san mateo, usa). survey consisting of questions sent to subscribers of the srlf mailing list via mailchimp software (atlanta, usa). frequencies and percentages were determined for categorical variables and median and interquartile range for continuous variables. the icus with or without psychologist were compared using nonparametric fisher exact test. stata used (lakeway drive, te, usa). results: responses were obtained from unique icus in france (n = ), belgium (n = ), switzerland (n = ), algeria (n = ), morocco (n = ) and tunisia (n = ). ( %) icus were part of public hospitals, ( %) of private facilities. ( %) icus cared for adult patients, ( %) for children. the median number of beds was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . ( %) icus were open to visitors / , ( %), to visitors > h/day and ( %) to visitors < h/day. psychological consults were established in ( %) wards ( icus did not answer). pediatric icus employed more psychologists than adult icus (p = . ). comparison of icus based on the presence or not of a psychologist appears in table . in icus where a consulting psychologist is available, their effective availability is . [ . - ] full time equivalent. consults are delivered to: patients ( %), families ( %) or healthcare workers ( %). out of the icus without a psychological consult, responders from ( . %) icus believe that a psychological consult is undesirable. out of the icus without psychological consult, ( %) responders cannot obtain a psychological consult, whatever the circumstances, ( %) can require an outside psychological consult when needed, while ( %) can require assistance from a psychologist working in another unit (several answers possible for each respondent). conclusion: psychologists consult in only half of adult icus but in almost all pediatric icus. % of icus are unable to provide a psychological consult. psychological consults are delivered in similar proportions to patients, their family and to a lesser extent to healthcare workers. responders from . % icus without an established psychological consult believe that the availability of a psychologist is undesirable. compliance with ethics regulations: na. rationale: comfort of patients in intensive care unit (icu) is now a real concern for the healthcare teams. perceived patient discomfort assessment is a daily practice for our staff. the primary objective of our study was to assess whether the overall discomfort score reported by patients hospitalized in a separate intermediate care unit differs from that reported by patients hospitalized in icu. a tailored multicomponent program consisting of assessment of icu-related self-perceived discomforts with a -item questionnaire, immediate and monthly feedback to healthcare teams and site-specific tailored interventions, was applied in our department, located in a general hospital, and comprising a -bed icu and a separate -bed intermediate care unit rationale: the transition period surrounding the discharge from icu to hospital ward is a critical period in the course of the patient. handoff of complex patients is at high risk for communication failures between providers, inaccurate cares and icu readmission. a transition program including a post icu follow-up has been proposed to improve handoff quality. post icu consults by icu team represent, also, an opportunity for improving feedback on the quality of icu cares. the goal of the present study is to assess the feasibility and the impact of a systematic early post-icu consult (epicuc) program on handoff quality in a bed mixed icu. patients and methods: before the development of the epicuc program, standardized handoffs were already applied including identified day and hour of discharge and both verbally communicate and written medical and nurse information for receiving team. from st march to th october , all patients who were discharged to the ward of our hospital were candidates for epicuc. epicuc were performed by icu staff (at least one icu physician) within the days following discharge. the epicuc consisted of a face-to-face discussion with the receiver team to assess the accuracy, completeness and understanding of passing information and of a patient visit. a standardized form was used for collecting data. the impact of epicuc on handoff quality was assessed by the number of communication failures and the number of patients in whom epicuc resulted in a management change. personal feeling of epicuc providers on its usefulness was assessed by a - rating scale. results: among the candidates for epicuc, were dead and already discharged alive from hospital at epicuc time. epicuc were performed in patients ( %) within ± days after icu discharge. epicuc ( %) were performed by both, nurse and icu physician. ( %) patients and receiver teams ( %) were available at epi-cuc time. epicuc duration was ± min. a communication failure was identified in epicuc ( %), either a rectification of passing information (n = ; %) and/or a change in patient management (n = ; %). the usefulness of the epicuc was rated at ± and ± by icu physicians and nurses, respectively. conclusion: the time spent for epicuc appears reasonable. epi-cuc identified a communication failure in one-third of handoffs and allowed care readjustment in one quarter of patients. factors associated with handoff failures will be presented during the congress. compliance with ethics regulations: yes. rationale: surviving a critical illness is a challenging condition for patients and relatives. the psychological aspects are directly affected by physical status and performance. patients can feel depressed or anxious facing difficulties during recovery time. the aim of this study was to correlate patients' perceptions of his health status and his clinical performance measured after icu discharge. patients and methods: this is a prospective pilot study of an icu follow-up clinic conducted in a single center from january to july . this clinic is multidisciplinary and includes two visits at and months after icu discharge. patients with more than days of icu los were eligible. all patients at and -m visit were evaluated with sf- , mwt, mrc and time-up-and-go test. we conducted an analysis comparing clinical performance data and qualitative data between and months after icu discharge. the investigation included patients who had at least days of icu length of stay. patients attended the consult at -m and patients attended the consult both times. the median age (iqr) was ( - ) and % were men. %, % and % of patients had medical, scheduled surgical and emergency surgical admission causes respectively, with median (iqr) saps iii score ( - ). %, % and % of patients had sepsis, delirium and mechanical ventilation as a support. the physical status was progressively increased overtime likewise the physical capacity assessed by sf- score with p-value . between and -m. however, no significant difference between the subjective dimension of sf- , which analyses the perception of the patient about his physical capacity, assessed at -m and at -m was demonstrated (p . ). in this pilot-phase of following a cohort of critically ill patients, the natural physical improvement does not seem to change the patient's perception of their performances. this paradigm rouses a different perspective that should take into account when setting up rehabilitation programs. compliance with ethics regulations: yes. post-traumatic stress disorder after discharge from an acute medical unit basma lahmer , naoufel madani , , jihane belayachi , , redouane abouqal rationale: post-traumatic stress disorder (ptsd) occurs after exposure to a traumatic event and comprises of symptoms of repeated re-experiencing of the said event, avoidance of reminders, emotional numbing and persistent hyperarousal. in individuals exposed to "medical stress", various studies found evidence of ptsd occurring after the onset, diagnosis, or treatment of physical illness. our study aims to determine ptsd's risk factors in patients of an acute medical unit (amu) after their discharge. patients and methods: it was a prospective, analytical study conducted over a period of months at an acute medical unit. we collected sociodemographic and clinical data, patients' medical history, and evaluated the symptoms of anxiety and depression during their stay using the hospital anxiety and depression scale (hads). the prevalence of severe ptsd symptoms was assessed with the impact of events scale-revised (ies-r) at weeks and months using a cutoff of . associations between ptsd as evaluated by ies-r at months and patients' characteristics, including hads scores at admission were investigated using unadjusted linear regression, for univariate and multivariate regression analysis. statistical analyses were carried out using spss for windows (spss, inc., chicago, il, usa). we included patients in our study with a mean age of . ± . . in our population, . % of patients scored higher than a ies-r cutoff at weeks compared to . % at months. the mean hads-anxiety score is . ± and that of the hads-depression score is . ± . . on one hand, higher hads-anxiety score during the stay in the amu was linked to higher ies-r scores at months β: rationale: objective of critical care includes restoration of functional capacities. prompt identification of muscle acquired weakness (icu-aw) is crucial to target efficient rehabilitation. in published literature, data of quadriceps strength (qs) cannot be compared because of insufficient standardization of measurement protocols. we recently validated a highly standardized protocol of qs measurement. in order to build basic and comparable knowledge and to identify the weakest patients, this study aimed to describe qs of critically ill (ci) patients during their short-term evolution, and to compare them to surgical (s) and healthy (h) subjects. patients and methods: this observational study included ci patients who spent at least days in icu, patients scheduled for elective colorectal surgery (s) and young healthy volunteers (h). maximal isometric qs was assessed using a handheld dynamometer (microfet ® ) and expressed in newton/kg (n/kg). dominant leg was tested in supine position using a highly standardized procedure. ci and s patients were tested at t (as soon as collaborative in icu) and month after discharge (m rationale: the post intensive care syndrome (pics) gathers various disabilities, associated with a substantial healthcare use. however, patients' comorbidities and active medical conditions prior to intensive care unit (icu) admission may partly drive healthcare use after icu discharge. to delineate the relative contribution of critical illness and pics per se to post-critical illness increased healthcare use, as opposed to pre-existing comorbidities, we conducted a population-based evaluation of patients' healthcare use trajectories. patients and methods: using discharge databases in a . -million-people region in france, we retrieved, over three years, all adult patients admitted in icu for septic shock or acute respiratory distress syndrome (ards), intubated at least days and discharged alive from hospital. healthcare use (days spent in healthcare facilities) was analyzed two years before and two years after icu admission. healthcare trajectories were next explored at individual level: patients were assembled according to their individual pre-icu healthcare use trajectory by clusterization with the k-means method. results: eight-hundred and eighty-two ( ) patients were included. median duration of mechanical ventilation was days (interquartile ranges [iqr] ; ), mean saps was , and median hospital length of stay was days (iqr ; ). prior to icu admission, we observed, at the scale of the whole study population, a progressive increase in healthcare use. however, clusterization of individual according to pre-icu healthcare trajectories identified patients with elevated and increasing healthcare use (n = ), and two main groups with low (n = ) or no (n = ) pre-icu healthcare use. patients with high healthcare use had significantly more comorbidities than those with low healthcare use. in icu, however, saps , duration of mechanical ventilation and length of stay were not different across the groups. interestingly, analysis of post-icu healthcare trajectories for each group revealed that patients with low or no pre-icu healthcare (which represented % of the population) switched to a persistent and elevated healthcare use during the two years post-icu. conclusion: for % of ards/septic shock survivors, critical illness appears to have a pivotal role in healthcare trajectories, with a switch from a low and stable healthcare use prior to icu, to a sustained higher healthcare recourse two-years after icu discharge. this underpins the hypothesis of long-term critical illness and pics-related quantifiable consequences in healthcare use, measurable at a population level. compliance with ethics regulations: yes. ( ) to describe the pre-hospital grading protocol developed by the northern french alps emergency network (trenau) for children, ( ) to evaluate its quality to detect the most severe trauma patients and ( ) to assess the accuracy of this procedure to perform an adequate triage. patients and methods: our regional trauma system included hospitals categorized as level i, ii or iii pediatric trauma centers. eachpatient was graded a, b or c by an emergency physician, according to the seriousness of their injuries at presentation on scene. the triage was performed according to this grading and the categorization of centers. this study is a registry analysis of an -year period ( to ). results: a total of children (mean age years, % were boys) with severe trauma were included in the cohort. fifty-seven, % and % of patients were admitted to a level i, ii and iii, respectively. road accident was the main mechanism of injury ( % of patients). thirtysix percent of patients had a severe trauma, defined as an injury severity score (iss) higher than . one quarter of patients had at least severe lesions and one-third of patients had a trauma brain injury. the pre-hospital gradation was closely related with injury severity score (iss) and intra-hospital mortality rate. the triage protocol had a sensitivity of % and a specificity of % to predict adequate admission of patients with iss more than . using a specific trauma score (including occurrence of death, an admission in intensive care unit and the need for urgent surgery), sensitivity and specificity reached and %, respectively. fourty-six percent of patients were not graded at the scene (non-graded group). undertriage rate was significantly reduced in the graded group compared with the non-graded group, ( % versus %), without significant modification of the overtriage rate ( % versus %). overall, mortality at discharge from hospital was %, but % in grade a patients. conclusion: implementation of a regional pediatric trauma system with a specific pre-hospital triage procedure was effective in detecting severe pediatric trauma patients and in lowering the rate of prehospital undertriage. compliance with ethics regulations: yes. rationale: critically ill children suffer from pathophysiological changes, leading to large between-subject variability in drug clearance. since piperacillin is eliminated mainly via the kidney, changes in renal function go along with a modified elimination, and possible subtherapeutic or toxic drug concentrations. we aimed to determine the most accurate glomerular filtration rate (gfr) estimation formula for assessing piperacillin clearance in critically-ill children. patients and methods: all children hospitalized in pediatric intensive care unit and receiving piperacillin were included. piperacillin was quantified by high performance liquid chromatography. pharmacokinetics were described using the non-linear mixed effect modeling software monolix. in the initial pharmacokinetics model, gfr was estimated according to the schwartz formula. in the study, gfr was estimated with additional formulas, developed with plasma creatinine and/or cystatin c. biases, precisions, spearman's rank correlation coefficient and normalized prediction distribution error (npde) were used to assess the models. results: we included children with a median (range) postnatal age of . ( . - ) years, body weight of . ( . - ) kg and estimated gfr according to the schwartz formula of . ( - ) ml min- . . m . piperacillin concentrations were best predicted with the model using the creatinine clearance. the correlations were most accurate: r = . between the population-predicted and the observed concentrations, r = . and r = . for the npde versus population-predicted concentrations and time, respectively. concerning the individual predicted concentrations, bias and precision were respectively − . mg l − and . mg l − . gfr estimations based on serum creatinine were higher than those based on cystatin c (p = . ). conclusion: in summary, the -h creatinine clearance is the best predictor of piperacillin clearance and this could be investigated for drugs with renal elimination. as a whole, literature and our findings strongly suggest using creatinine clearance to also estimate gfr in critically ill children. the gap between the gfr estimations is large depending on the formulas, with higher estimations with equations based on serum creatinine. compliance with ethics regulations: yes. rationale: acute pancreatitis (ap) incidence have increased dramatically over the past years. new guidelines in were recently published in order to standardize the definition and management of ap. the aim of this study is to describe the management of children that were diagnosed with ap from the pediatric intensive care unit (picu) in two french hospitals. patients and methods: this retrospective cohort study included children aged under years old, who were admitted to the picu of robert-debré hospital and trousseau from to with a discharge diagnosis of ap. data collected included management, severity and outcomes. we have also obtained data on clinical, biological and radiological presentation. results: sixty patients were included, the median age was years ( - ) and % had a co-morbidity mainly hematologic ( / ). most of the ap were moderate ( %) or severe ( %). hemodynamic failure was the main reason for picu admission requiring a median fluid resuscitation ml/kg complemented by a median intravenous fluid therapy of ml/kg/h ( - ) during the first h. twenty patients ( %) required mechanical ventilation. fasting has been instituted in patients ( %) for a median of days ( - ), whereas patients ( %) received parenteral nutrition, only patients ( %) received enteral nutrition. antibiotic therapy was given to patients ( %) including % for curative therapy. the median length of stay in picu was days ( ) ( ) ( ) ( ) ( ) . the mortality rate was %. conclusion: this is the first french study which precisely described the management of patients with ap in picu. it highlighted the differences withthe new international guidelines. this study could improve the management of pa in picu and open research perspectives. compliance with ethics regulations: yes. rationale: apheresis and therapeutic plasma exchange (tpe) for children diseases has been poorly investigated in mostly small-uncontrolled studies. the purpose of this study is to describe indications and safety of tpe in children. patients and methods: in this single center and retrospective study, we included patients who underwent tpe with an age < years old in the pediatric center of necker-enfants-malades hospital from january to december . data were retrospectively collected in an electronic case report form via a web-based data collection system. results: patients with a median age of . years [range . ; . ] were selected. they achieved a total number of procedures. indications were antibody-mediated rejection (n = ; %) or desensitization therapy (n = ; %) for solid organ or hematopoietic transplantations; microangiopathy (n = ; %); renal diseases (n = ; %) and pediatric inflammatory diseases (n = ; %); or hyperviscosity syndrome (n = ; %). each patient had an average of procedures for the first session [range ; ] with a median volume of ml [range ; ml] corresponding to a median (rang) total plasma volume (tpv) equivalent of . l/m [ . - . ]. within days since the beginning of sessions, patients ( %) present a total of adverse events (aes) potentially related to tpe. there was a median (range) of aes/patients [ - ]. there was no association between aes and diseases, severity of patients, venous access, plasma substitute and body weight. few of aes (n = for patients) were potentially life-threatening and concerned mostly critically ill children. allergic reactions represented only aes for patients (grade i n = ; grade ii n = ; grade iii n = ). at the months endpoint, ( %) patients died and ( %) patients had severe persistent disease. no death had been related to the tpe process. we describe one of the largest retrospective pediatric cohort updated to the last international recommendations. tpe in children is performed for specific and potentially refractory disease. it is feasible without a major risk of life threatening adverse events. compliance with ethics regulations: yes. yacine benhocine university hospital nedir mohamed, tizi-ouzou, algeria correspondence: yacine benhocine (yacine @yahoo.fr) ann. intensive care , (suppl ):f- rationale: although analysis of literature data shows that implantable chamber catheters (iccs) are less at risk of infectious complications than other central venous catheters, these complications can be serious, which may differ from ongoing treatments such as chemotherapy, and may lead to the removal of the implanted device. the literature on preventing these infections is quite disparate, as practices. purpose: to evaluate the incidence of infections, to identify responsible germs and to measure the impact of preventive measures. patients and methods: prospective, descriptive, mono-centric study, from january to january . all patients under the age of who have benefited from an implantable chamber catheter, whose insertion procedure is as follows: local anesthesia, surgical asepsis (polyvidone iodine) in an operating room, double disinfection, no antibiotic prophylaxis, routes used: subclavian ( %), internal jugular ( %) by anatomic registration. the main criteria of judgment are: the incidence of local and general infections, their time of onset, responsible microorganisms. statistical analysis used the statistical package for the social sciences software. results: patients were included, the average incidence density of early infection is . / day-catheters. the time of onset of infection is essentially between the nd and rd week post-exposure, of which % is general infection. ablation involved % of infected catheters. the causative organisms are mainly gram-positive cocci ( . %), gram-negative bacilli are less involved ( . %), with a significant number of candida infections ( %). discussion: higher incidence of data from the literature. to remedy this requires the implementation of additional hygiene measures: antiseptic showers preoperatively, chlorhexidine??, and practice changes: echo guidance, antibiotic prophylaxis or locks? second generation catheters? our practices are disparate especially since the recommendations specifically concerning the prevention of infectious risk associated with internationally published iccs are rare. conclusion: at the end of this work, our perspectives are to: update the procedure, highlight risk factors on which it is possible to act, the adhesion of the different staff to the protocols. compliance with ethics regulations: yes. rationale: the sepsis and septic shock pediatric guidelines advise to treat patients using care bundles. in the first hour, the «resuscitation bundle» contains an appropriate fluid resuscitation, a broad-spectrum antibiotics administration after blood cultures, and initiation of inotrope if needed. the objectives were to evaluate the resuscitation bundle compliance in a cohort of septic children with cardiovascular dysfunction, and to analyze the effect on severity and outcome in pediatric intensive care unit (picu). patients and methods: retrospective analysis of the diabact iii study. this study analyzed the care course of children with severe community-acquired bacterial infection, hospitalized in picus in france's west departments, between august and january . children with severe sepsis and cardiovascular dysfunction were retrospectively included. results: we included children of whom ( . %) had compliant bundled care. the severity scores at picu's admission were similar between groups (p = . for the prism score and . for the pelod ). there was the same proportion of fluid-refractory shock (p = . ), mechanical ventilation (p = . ), neurological dysfunction (p = . ) and cardiac arrest (p = . ). in the «resuscitation bundle compliant» group, . % died versus . % in the other group (p = . ). we highlighted a severity bias: the sickest patients were more likely to receive compliant bundled care. conclusion: in our cohort, the resuscitation bundle's compliance was low. we did not show some effect on morbidity nor mortality. however, this study helps understand the factors associated with resuscitation bundle's compliance. rationale: nosocomial infections with extended-spectrum β-lactamase (esbl) producing gram-negative bacilli (gnb) are an important cause of hospital morbidity and mortality. the objective of this study was to determine the incidence and risk factors of nosocomial esbl-producing gnb infections in a paediatric intensive care unit (picu). patients and methods: a prospective surveillance study was performed from january through march in a picu. all patients hospitalized for more than h were included. centers for disease control and prevention criteria were applied for the diagnosis of nosocomial infection. results: during the study period, patients (median age: ± days) were included. the average length of stay was ± days with a total of , days of hospitalization. newborns accounted for . % of patients. sixty-two per cent of patients were colonized with multi drug resistant gram-negative rods, on admission or during their stay in the picu. one hundred and nineteen bacterial infectious episodes were registered ( . / patient days). one hundred infectious episodes were caused by a gnb and ( . %) by esbls producing gnb with an incidence of . / patient days (bloodstream infections: episodes, ventilator acquired pneumonia: episodes). esbls producing gnb infection had a specific incidence of . per catheter-days, and . per mechanical ventilation-days. fifty-nine percent of patients infected with esbls producing gnb had a prior digestive colonization with a multidrug-resistant gnb. forty-one episodes ( %) occurred in patients with central venous catheters. klebsiella pneumoniae was the most frequently isolated bacteria ( . %). mortality in the esbls producing gnb group was high ( . %). associated factors of nosocomial esbls producing gnb infection were mechanical vrntilation (p < . ), central venous catheterization (p < . ) and colonization with multiple drug-resistant gram-negative bacteria (p < . ). conclusion: nosocomial esbl-producing gnb infection had an incidence of . per patient days in our unit and seems to increase the mortality rate. factors associated with this infection were identified. marie lemerle , aline schmidt , valérie thepot-seegers , achille kouatchet , valérie moal , mélina raimbault , corentin orvain , jean-francois augusto , julien demiselle chu angers, médecine intensive réanimation, angers, france; chu angers, maladie du sang, angers, france; chu angers-ico, angers, france; chu angers, pharmacie, angers, france; chu angers, labora-toire de biochimie, angers, france; chu angers, néphrologie dialyse transplantation, angers, france correspondence: marie lemerle (marielemerle@yahoo.fr) ann. intensive care , (suppl ):f- rationale: acute kidney injury (aki) is associated with high morbidity and mortality in the setting of tumor lysis syndrome (tls). thus, strategies aimed at preventing aki occurrence represent a major goal to improve prognosis of patients with tls. the role of hyperphosphatemia as a risk factor of tls has been poorly analyzed. the aim of this study was to study the association between hyperphosphatemia and aki, and to determine whether a cut-off value of phosphatemia or phosphatemia's variation was associated with aki development during tls. patients and methods: in this retrospective and monocentric study, we included all patients with tls and whithout aki at admission, admitted to hematology, nephrology and intensive care units of the university hospital of angers between / / and / / . results: one hundred and thirty tls episodes were identified in patients. aki developed during episodes of tls ( %). hospital mortality was much higher in aki patients ( . % versus . %, p = . ). phosphate maximal values ( . ± . versus . ± . ) and ldh maximal values ( . ± . versus . ± . ) were higher in tls with aki, before aki occurrence (p = . and p = . , respectively). we found no association between the other biological parameters of tls and aki (serum calcium, uric acid and potassium). after adjustment for cofounders, there was a strong association between a rise in phosphate level of . mmol/l (hr . ic % [ . - . ], p < . ), exposure to platinum salts (hr . ic % [ . - . ], p = . ) and increasing maximal ldh value (hr per ui/l increase . ic % [ . - . ], p = . ) with aki. conclusion: this study highlights the utmost importance of serum phosphate in the setting of tls: phosphate is an early relevant biomarker for the risk of aki development. further studies are needed to assess whether aggressive prophylactic treatment to control serum phosphate concentration, such as renal replacement therapy before aki onset, constitutes a valuable approach. compliance with ethics regulations: yes. retrospective cohort of patients admitted to the medical icu of university affiliated hospital after carts treatment between august and august . results: of the patients treated by carts in the haematology department, ( %) were subsequently admitted to icu. median age was [ . - . ] years, and ( . %) were female. carts were indicated for r/r lymphoma. the median time between carts injection and icu admission was [ . - . ] days. all patients had cytokine release syndrome (crs), and ( . %) developed car-related encephalopathy syndrome (cres). median sofa score and saps were [ - . ] and [ . - . ], respectively. four ( . %) patients had hypotension treated by fluid bolus (n = ) or vasopressors (n = ), and ( . %) had acuterespiratory failure requiring oxygen therapy (n = ) or mechanical ventilation (n = ). six ( . %) patients had neurological symptoms (impaired consciousness n = , confusion n = , transient aphasia n = ), of whom one developed refractory convulsive status epilepticus afterwards. all patients received broad spectrum antibiotics, of whom ( . %) had documented infections. six ( . %) patients received interleukin- inhibitor (single dose n = , multiple doses n = ), and ( . %) received intravenous dexamethasone. one patient died in the icu from septic shock. median icu and hospital length of stays were [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and [ . - . ] days, respectively. two ( . %) patients died from relapsing malignancy before hospital discharge. three months after icu admission, four ( . %) patients were alive in complete remission. conclusion: more than % of patients treated with carts required icu admission for the management of a crs or a cres. early icu admission, close collaboration between haematologists and intensivists, and prompt administration of appropriate therapy (il- inhibitor and/or dexamethasone) and supportive care resulted in a good prognosis. compliance with ethics regulations: yes. rationale: tisagenlecleucel (ctl ) is a chimeric antigen receptor t cell therapy that reprograms autologous t cells to target cd + leukemia cells, approved in the us since august and in the eu since august for children and young adult (< years old) with relapsed/refractory b-cell acute lymphoblastic leukemia (b-all). this study reports the experience of picu management of ctl toxicity in patients treated in robert-debré university hospitals. patients and methods: all patients (age < years old) treated by tisagenlecleucel infusions between march , and september , , included in sponsored-clinical trials or treated within the french compassionate program or with the commercial product, were retrospectively analyzed. results: twenty-four patients were infused and patients ( %) were managed in picu for stays. ( stays: n = and stays: n = ). median age at picu admission was . years old [ . ; . ] with a median delay after car-t cells infusions of days [ . ; ] . the median length of stay in picu was days [ . ; ] with a max at days. cytokine release syndrome (crs) was the main indication of picu hospitalization ( . %, n = ) with grade (n = ) and grade (n = ) according to american society for transplantation and cellular therapy (astct) consensus grading system and treated by corticosteroid (n = . ) and tocilizumab (n = , only one infusion). norepinephrine was the only vasopressor used. the median vaso-inotrope score (vis) for grade was [ . ; . ] with a maximum at . neurologic toxicity was observed in patients with a grade (status epilepticus) and grade (focal edema on neuroimaging with depressed level of consciousness) according to immune effector cell-associated neurotoxicity syndrome (icans) grading system from astct consensus. the status epilepticus was managed with anti-epileptic drugs without mechanical ventilation. the focal edema was related to hhv and toxoplasmosis encephalitis. evolution was positive with foscavir and ganciclovir and days of mechanical ventilation. one patient was hospitalized for septic shock secondary to gram-negative central line bloodstream infection in aplasia, with a vis score at . evolution was favorable with antibiotics and central line removal. no death in picu from severe tisagenlecleucel toxicity was observed since the beginning of the car-t cells program. conclusion: toxicity profile of tisagenlecleucel required frequent and early picu hospitalization after infusions for severe crs and icans management. compliance with ethics regulations: yes. rationale: car-t cell (chimeric antigen receptor t) therapy is a promising treatment in refractory acute lymphoid leukemia (all) and diffuse large b cell lymphoma (dlbcl). the main complication consists in a cytokine release syndrome (crs) leading to an inflammatory state that can be very severe with life-threatening organ failure. neurological toxicity is also reported. we aim to describe car-t cells-related complications in icu patients. patients and methods: this is a single-center prospective study conducted between july and august . all the patients who have received car-t cells and who required icu admission were included. crs grading was defined according to the most recent classification of the asbmt and neurological toxicity was assessed with the cartox scale. each admission is considered independent and therefore corresponds to one patient. results: admissions, representing patients ( men and women), were considered. the median age was years . twothirds of the patients have been diagnosed with dlbcl (n = , %) and one-third with all (n = , %), months [ - ] ago. they had received lines [ ] [ ] of chemotherapy and had a high tumor burden ( % of lymphomas classified stage iv). the majority of the patients was admitted because of hemodynamic failure (n = , %) or respiratory failure (n = , %), days [ ] [ ] [ ] [ ] [ ] after car-t cells infusion. sofa at admission was [ ] [ ] [ ] [ ] [ ] . all the patients presented at least one complication ( figure) , the most common being crs (n = , %) with a median grade of [ ] [ ] . neurological toxicity was reported in ( %) patients (worst grade at [ ] [ ] [ ] ). documented bacterial infection involved % of the patients and consisted in catheter-related infections for half of the cases. in the icu patients were managed with fluid resuscitation (n = , %) during the first day, vasopressors (n = , %) and broad spectrum antibiotics ( %). a single patient required mechanical ventilation and two patients underwent dialysis. tocilizumab (anti-il receptor) was given to patients ( % of crs) in a median time of . h [ . - . ] after icu admission. patients ( %) received corticosteroids. the median icu length of stay was . days [ ] [ ] [ ] [ ] . patients ( %) died in the icu and hospital mortality was %. the -fluorouracil ( -fu)-induced hyperammonemic encephalopathy is a rare but serious -fu adverse drug reaction, which could require the admission of patients in intensive care unit (icu). given the paucity of data regarding this -fu adverse drug reaction, we performed a retrospective national survey from the french pharmacovigilance database to better characterize -fu-induced hyperammonemic encephalopathy and its management. patients and methods: since the inception of the french pharmacovigilance database, we identified all patients that experienced -fu-induced encephalopathy. variables regarding epidemiology, characteristics, management and prognosis of these patients were collected and analyzed. results: from from to years-old, % of women) were included. overall mortality was % (n = ) and % (n = ) of patients were admitted in icu. the -fu-induced hyperammonemic encephalopathy started [ ] [ ] [ ] [ ] days after the onset of -fu infusion. the most common neurological disorders were consciousness impairment, confusion and seizures. abnormalities in ct scan, mri, electroencephalogram and lumbar puncture were found in %, %, % and % of the whole population respectively, similar in icu and non-icu patients. ammonemia was dosed in % of the whole population and in % of icu patients. hyperammonemia tended to be higher in icu than in non-icu patients ( [ - ] vs. [ - ] µmol/l, respectively, p = ns) and in patients with the lowest glasgow outcome scale, but was not different between survivors and non-survivors. among icu patients, % required mechanical ventilation and % anti-epileptic drugs administration. besides -fu discontinuation, lactulose intake, renal replacement therapy or ammonium chelators were used to decrease hyperammonemia in %, % and % of patients respectively. a complete neurological recovery was observed in up to % of icu and non-icu patients within a delay of [ - ] days. a dihydropyrimidine deshydrogenase (dpd) deficiency was found in % of tested patients. a -fu rechallenge was considered in % (n = ) of patients with complete neurological recovery, including a patient with a partial dpd deficiency, within a delay of [ - ] days after recovery. a -fu-induced hyperammonemic encephalopathy relapse was observed in % of patients with -fu rechallenge. no relapse was observed when -fu rechallenge was performed with a decreased -fu dosage. conclusion: we report the first national survey and the largest cohort of patients with -fu-induced hyperammonemic encephalopathy so far. this serious -fu adverse drug reaction must be known by intensivists, since more than half of patients are admitted in icu and specific treatments are available. compliance with ethics regulations: yes. immune related adverse events: a retrospective look into the future of oncology in the intensive care unit adrien joseph , annabelle stoclin , antoine vieillard-baron , guillaume geri , jean-marie michot rationale: immune checkpoint inhibitors (ici) represent a paradigmatic shift in oncology. with their new position as a mainstay in cancer treatment, new toxicities called immune related adverse events (iraes) have emerged. patients and methods: retrospective study including patients admitted in the icu within days after treatment with an ici in french hospitals. patients were classified into groups according to the reason for admission: irae, intercurrent adverse event (intae) or event related to tumor progression (tumprog). results: patients were admitted during the course of an ici treatment, including irae, intae and tumprog, with a significant increase between (n = ) and (n = patients, p for trend < . ). irae included pneumonitis, colitis, diabetes complications, hypophysitis, nephritis, myocarditis and cardiac disorders, hepatitis or allergic reaction and meningitis. the immune related nature of the complication was known before admission in only ( %) cases. mean age was (± ) years and % had a performance status of - . primary tumors were melanomas ( , %), non-small cell lung cancers ( , %) , urothelial carcinomas ( , %) and hodgkin lymphomas ( , %) . ici at the time of admission included anti-ctla ( , %), anti-pd /pdl ( , %) and anti-ctla /anti-pd combination in ( %) patients. mean duration of stay in the icu was . (± ) days. three patients required vasopressor therapy alone, with mechanical ventilation and one with extracorporeal membrane oxygenation. three patients required non-invasive ventilation and renal replacement therapy alone. six required only endocrine or electrolytic equilibration and others did not receive any form of organ support. icu mortality was %. compared with other admissions, anti-ctla or anti-ctla /anti-pd combination treatments were associated with irae diagnosis (or = . [ . - . ] , p = . for anti-ctla and . [ . - . ] for anti-ctla /anti-pd , p = . ) and so was the diagnosis of melanoma ( . [ . - . ] , p = . ). there was no difference in terms of icu and post-icu survival between irae (median post-icu survival months [ -na]), intae ( . [ . -na]) and ). six patients admitted for an irae were rechallenged with the same ici after icu discharge and achieved complete response. conclusion: we conducted the first study describing patients admitted in the icu for iraes. their specific and heterogeneous profile, along with the expected increase in the number of admissions, underlines the need for an in-depth knowledge for icu physicians in order to take part in the multidisciplinary care required by these patients. compliance with ethics regulations: yes. rationale: patients with advanced-stage non-small-cell lung cancer have high mortality rates in the intensive care unit (icu). in this context, acute respiratory failure due to cancer involvement is the worst situation. in the last two decades, targeted therapies have changed the prognostic of patients with lung cancer outside the icu. unlike cytotoxic chemotherapy, the fast efficacy of targeted therapies led some intensivists to use them as rescue therapy for icu patients. we sought to investigate the outcomes of patients with lung cancer involvement responsible for acute respiratory failure and who received tyrosine kinase inhibitor during icu stay. patients and methods: we performed a national multicentric retrospective study with the participation of the grrroh (groupe de recherche en réanimation respiratoire en onco-hématologie). all patients with non-small-cell lung cancer admitted to the icu for acute respiratory failure between and were included in the study if a tyrosine kinase inhibitor was initiated during icu stay. cases were identified using hospital-pharmacies records. we collected demographic and clinical data in icu charts. vital status was assessed at the time of study completion (august ). the primary outcome was overall survival days after icu admission. results: twenty-nine patients (age: ± years old) admitted to a total of icus throughout france were included. seventeen patients ( %) were nonsmoker. the most frequent histological type was adenocarcinoma (n = , %) and a majority had metastatic cancer (n = , %). epithelial growth factor receptor mutation was the most common oncologic driver identified (n = , %). during the icu stay, ( %) patients required invasive mechanical ventilation, ( %) catecholamine infusion, ( %) renal replacement therapy and one ( %) extracorporeal membrane oxygenation. in addition to tyrosine kinase inhibitor, ( %) patients received steroids (beyond . mg/kg/day) and ( %) cytotoxic chemotherapy during icu stay. seventeen patients ( %) were discharged alive from icu and ( %) were still alive after days (see kaplan-meier curve figure) . moreover, patients ( %) were alive one year after icu discharge. conclusion: despite a small sample size this study showed that, in the context of lung cancer involvement responsible for acute respiratory failure, the use of tyrosine kinase inhibitor should not be refrained in patients with severe condition in icu. compliance with ethics regulations: yes. rationale: acute respiratory failure is the leading reason for intensive care unit (icu) admission in immunocompromised patients and the need for invasive mechanical ventilation has become a major clinical end-point in randomized controlled trials (rct). however, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. this study explores how this outcome varies across icus. patients and methods: hierarchical models and permutation procedures for testing multiple random effects were applied on both data from observational cohort (the trial-oh study: patients, icus) and randomized controlled trial (the high trial: patients, icus) to characterize icu variation in intubation risk across centers. results: the crude intubation rate varied across icus from % to % in the observational cohort and from to % in the rct. this center effect on the mean icu intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p-value = . , median or . [ . - . ]; rct: p-value: . , median or . [ . - . ]). two icu-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to icu admission) and could partly explain this center effect. in the rct that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. conclusion: invasive mechanical ventilation has become an important endpoint in immunocompromised patients with acute respiratory failure. however, we found significant variation in intubation risk across icu in both an observational cohort and a randomized controlled trial. our results highlight the need to take into account center effect in analysis because it could be an important confounder. reasons for heterogeneity are various (case-mix differences, center practices). this gives opportunities to future improvement in care management and study design. compliance with ethics regulations: yes. rationale: influenza virus (iv) infection is a major cause of ards that has been the focus of attention since the pandemic h n (h n pdm ) iv. although iv-mediated damage of the airway has beenextensively studied emphasizing specificity compared to other causes of ards, the impact of iv infection on the prognosis of ards patients, compared to the other causes of ards, has been few assessed. patients and methods: systematic detection of iv in times of epidemic using rt-pcr in respiratory specimen is routine practice in our icu along with prospective data collection of patients admitted to our icu for ards with pao /fio ratio ≤ mmhg. all patients received lung-protective ventilation, the sequential organ failure assessment (sofa) score was calculated on the first days of mechanical ventilation. the primary endpoint compared the -day survival from the diagnosis of ards between patients with and without iv infection. results: from october, to may, , patients (pts) [median saps ii score = ( - ); age years ( - ); pao / fio ≤ mmhg, n = ( %)] were admitted to our icu for ards with pao /fio ratio ≤ mm/hg, including pts ( %) with iv infection (h n pdm iv a, n = ; h n a virus, n = ; b virus, n = ; associated bacteria, n = ). other main causes of ards were bacterial pneumonia without iv ( %), aspiration ( %), non-pulmonary sepsis ( %). ( %) received prone positioning, and ( %) extra-corporeal membrane oxygenation. the overall mortality rate at day- for the entire population was % ( pts ( %) with iv infection versus pts ( %) without iv infection, p = . ). kaplan-meier survival curves showed that survival was significantly higher in patients with iv infection than in those without iv infection. iv infection remained independently associated with a better prognosis at day- when entered as dichotomous variable (iv infection, yes/no) (adjusted hazard ratio (hr) = . , % ci . - . , p = . ) and when iv infection only was distinguished from other causes of ards including mixed infection iv plus bacteria (adjusted hr = . , % ci . - . , p = . ). of note, within the first days of mechanical ventilation, non-pulmonary sofa scores were significantly lower in iv patients although similar pulmonary sofa scores. conclusion: our results suggest that patients with iv related ards have less severe non-pulmonary organ dysfunctions than those with ards from other and a lower mortality at day- despite similar ards severity. compliance with ethics regulations: yes. rationale: acute respiratory distress syndrome (ards) remains frequent in intensive care unit (icu) with % to % mortality. according to joint theater trauma system, ards occurs among % of war casualties: direct lung trauma, blast lesions, burn, massive transfusion and systemic inflammatory response syndrome lead to ards development. however, there is no data reporting ards among french evacuated casualties from forward environment. our study's aim is to describe ards incidence and its severity concerning medical evacuations from war theater. patients and methods: this is an observational retrospective multicentric study analyzing all evacuated patient from war theater and admitted in icu. all patients developing ards according to berlin definition have been included. study has been approved by local ethic committee. primary study endpoint was ards developing. second study endpoints were ards severity, duration of invasive ventilation, ards treatments, icu length of stay and mortality. results: patients have been admitted in icu between and . have been excluded. a total of patients have been analyzed. % (n = ) were military aged ( - ) years. % (n = ) developed ards. we found % (n = ) war casualties, % (n = ) trauma not related to war and % (n = ) medical patients. among severe trauma, median iss was ( - ), ais thorax ( ) ( ) ( ) , and % benefited from surgery on forward environment and % (n = ) received massive transfusion. % (n = ) suffered from mild ards, % (n = ) moderate ards and % (n = ) severe ards. evacuation time was ( - ) h. at admission in icu, pao /fio ratio was ( - ) (fig. ). all patients were intubated. ards treatments used were curarization ( %, n = ), prone position ( %, n = ), inhaled nitric oxide (noi) ( %, n = ), almitrine ( %, n = ) and extracorporeal life support (ecls) ( %, n = ). invasive ventilation duration was ( - ) days, length of stay ( - ) days, and -month mortality % (n = ). conclusion: according to our study, ards among french evacuated patients from war theaters remains frequent: it occurs on % among icu admitted patients. % suffer from severe ards with % global mortality. those datas are consistent with us studies. also, we wonder if we must adapt our treatment capacities on forward environment for the most severe patients. in us army, a specialized team (acute lung rescue team) is trained to care the most hypoxemic war casualties with more treatment options as noi, ecls. compliance with ethics regulations: yes. rationale : we recently reported that septic shock patients with pneumonia exhibit a high risk of icu-acquired pneumonia, suggesting that a primary pulmonary insult may drive profound alterations in lung defence towards secondary infections ( ) . given their importance in lung immune surveillance, alveolar macrophages (am) are likely to play a pivotal role in this setting. the objective of this experimental study is to address the impact of primary pulmonary or non-pulmonary infectious insults on lung immunity. patients and methods: we established relevant double-hit experimental models that mimic common clinical situations. c bl/ j mice were first subjected either to polymicrobial peritonitis induced by caecal ligation and puncture (clp), or to bacterial pneumonia induced by intra-tracheal instillation of staphylococcus aureus or escherichia coli. respective control mice were subjected to sham laparotomy or intratracheal instillation of phosphate-buffered saline. seven days later, mice that survived the primary insult were subjected to intra-tracheal instillation of pseudomonas aeruginosa (pao strain). we assessed survival and pulmonary bacterial clearance of post-septic animals subjected to p. aeruginosa pneumonia, as well as the distribution and functional changes in alveolar macrophages. results: when compared to sham-operated mice, post-clp animals exhibited increased susceptibility to secondary p. aeruginosa pneumonia as demonstrated by defective lung bacterial clearance and increased mortality rate ( % vs. %, p < . ). in contrast, all postpneumonia mice survived and even exhibited improved bacterial clearance as compared to their control counterparts. when addressing whole-lung immune cell distribution at the time of second hit (day ), amounts of am were decreased in post-clp mice while preserved or even increased in post-pneumonia mice. antigen-presenting functions of am appeared similar in all conditions. percentages of apoptotic (annexinv + ) and necrotic ( -aad + ) am were comparable at day and day after the first hit. interestingly, both ly c high and ly c low monocytes were sustainably increased in the lungs of post-clp mice, while only transiently expanded following pneumonia, suggesting that differences in am counts could be related to modulated turnover from precursor monocytes. conclusion: using clinically relevant double-hit experimental models, a primary pulmonary infection conferred resistance to secondary bacterial pneumonia. ongoing investigations are aimed at addressing the antibacterial am functions, as well as the turnover-driving mechanisms.compliance with ethics regulations: yes. rationale: little is known on the role of exit-site signs in predicting intravascular catheter infections. the current study aimed to describe the association between local signs at the exit-site and catheter-related bloodstream infection (crbsi), which factors substantially influenced local signs and which clinical conditions may predict crb-sis if inflammation at insertion site is present. patients and methods: we used individual data from multicenter randomized-controlled trials in intensive care units (icus) that evaluated various prevention strategies regarding colonization and crbsi in central venous and arterial catheters. we used univariate and multivariate logistic regression stratifying by center in order to identify variables associated with redness, pain, non-purulent discharge, purulent discharge and ≥ local sign and subsequently evaluate the association between crbsi and local signs. moreover, weevaluated the role of thedifferent local signs for developing crbsi in subgroups of clinically relevant conditions. results: a total of patients, , catheters ( , catheterdays) and crbsi ( . %) from icus withdescribed local signs were included. redness, pain, non-purulent discharge, purulent discharge and ≥ local signs at removal were observed in ( . %), ( . %), ( . %), ( . %) and ( . %) episodes, respectively. the sensitivity of ≥ local sign for crbsi was by . %, whereas the highest specificities were observed for pain ( . %) and purulent discharge ( . %). positive predictive value (ppv) was low for redness ( %), pain ( %), non-purulent discharge ( %) and ≥ local sign ( %), but increased for purulent discharge ( . %). negative predictive values were high for all local signs. after adjusting on confounders, crbsi was associated with redness, non-purulent discharge, purulent discharge and ≥ local sign (fig. ). conditions independently associated with ≥ local sign were age ≤ years old (or . , % ci . - . , p < . ), sofa score (sofa < or . , % ci . - . , p < . ), non-immunosuppression (or . , % ci . - . , p < . ), catheter maintenance > days (or . , % ci . - . , p < . ) and insertion site (or for subclavian site . , % ci . - . , p < . ). however, the presence of ≥ local sign was more predictive for crbsi in the first days of catheter maintenance (or . , % ci . - . vs. > catheter-days or . , % ci . - . , p heterogeneity = . ). conclusion: this post hoc analysis showed that local signs were related to crbsis in the icu. local signs were independently associated with specific patient's and catheter's conditions. in the first days of catheter maintenance, local signs were predictive for crbsi. compliance with ethics regulations: yes. rationale: pneumococcal meningitis (pm) is the leading cause of bacterial meningitis in adult patients requiring icu admission and is associated with a high case fatality rate (cfr), ranging from to more than % ( ) ( ) ( ) . patients with pm may develop sepsis or septic shock that may impact management and outcomes. we aim to describe the epidemiology and outcomes of pm associated with sepsis in adult patients in france. we analysed the occurrence of pm with sepsis from to in adult patients, using the national french hospital database pmsi (programme de médicalisation des systèmes d'information). for all analyses, only the first hospital admission was considered. cases were identified using a combination of a diagnosis code for pm plus a diagnosis code for sepsis (either a code for organ failure or a procedure code for organ support). data recorded included comorbidities ( ), characteristics of the hospital stay, severity of the patients including major intracranial complications and characteristics of the infection. costs and endpoints were determined at the end of all the hospital stays related to the first admission for pm with sepsis. standardized incidence, hospital mortality, and cfr were estimated. temporal trends were assessed using cochran armitage tests of trends and linear trend analyses. results: a total of pm with sepsis aged ≥ years were hospitalized in france during - . the incidence of pm decreased from . to . per m inhabitants (p < . ) (fig. ) . most of them came from home ( %), were admitted in an academic institution ( %) and benefited from icu ( %). their median age was [ ; ] years. twothird of them had at least one comorbidity. the initial neurological presentations included coma ( %), focal signs ( %), seizures ( %) and brain stem involvements ( %). the saps ii score was [ ; ] points. the main neurological complications were cerebrovascular complications ( %), cerebral abscess ( %) and hydrocephaly ( %). pm was associated with pneumococcal septicaemia or pneumococcal pneumonia in % and % of cases respectively. the length of icu and hospital stays were [ ; ] and [ ; ] days respectively and only icu length of stay decreased over time (p < . ). the prognosis was poor since only . % of the patients were discharged to home. indeed, . % of them died and % were transferred to rehabilitation units. no temporal trends could be observed for these outcomes. the average hospital costs per case were , € [ . ; . ] . conclusion: pm with sepsis in adult in france remained a real burden associated with a high mortality rate, and disability. compliance with ethics regulations: na. rationale: mucormycosis is an emerging fungal infection, especially in patients with hematological malignancies. although this infection may lead to multi organ failure, no study has been dedicated to critically ill patients with hematological malignancy. the primary objective was to assess outcome in this setting. the secondary objective was to assess prognostic factors. patients and methods: this retrospective cohort study was performed in icus. critically ill adult patients with hematological malignancies and mucormycosis were included between and . mucormycosiswas classified as "probable"or "proven" regarding eortc criteria. variables are reported as median [iqr] or number (%). adjusted analysis was performed using cox model. results: twenty-six patients were included with a median age of years [iqr, . acute leukemia was the most frequent underlying disease (n = , %). nine patients ( %) were allogeneic stem cell transplantation (sct) recipients. nineteen patients ( %) had neutropenia and patients ( %) had received steroids. the main reason for admission was acute respiratory failure (n = , %) followed by shock (n = , %). the median sofa score at admission was [iqr, - ] points. only patients ( %) had received prior anti-fungal prophylaxis effective against mucorales. mucormycosis was "proven" in patients and "probable" in patients. diagnosis was made by histopathologic examination in patients, direct microscopy or culture in , and polymerase chain reaction in . rhizopus and mucor were the most frequent documented species. seven patients ( %) had concurrent aspergillus infection. mucormycosis was diagnosed day [− to + ] after icu admission. ten patients ( %) had pulmonary involvement whereas five patients ( %) had rhino-cerebral involvement. infection was disseminated in eight patients ( %). twenty-two patients ( %) were treated with liposomal amphotericin b. twelve patients ( %) received antifungal combination including posaconazole in . eight patients ( %) underwent curative surgery. multiple organ failure was frequent, patients ( %) requiring invasive mechanical ventilation (imv), ( %) vasopressors, and ( %) renal replacement therapy. icu and hospital mortality rates were % and %, respectively. only two patients were alive at day . three variables were associated with mortality in a cox model including allogeneic sct . ]; figure), sofa score (hr . [ % ic . - . ]) and dual therapy (hr . [ % ic . - . ]) (fig. ) . conclusion: mucormycosis is associated with a high mortality rate in patients with hematological malignancies, especially in allogeneic sct recipients. futility of icu management in these patients is to be considered and strategies aiming to improve these patients' outcome are urgently needed. compliance with ethics regulations: yes. rationale: sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. several mediators, alone or in combination, were proposed to characterize individual response, but none was proven to have good external validity. the aim of this work was to establish whether some combinations are linked to clinical phenotypes in patients with presumed sepsis, using the data collected in the captain multicenter cohort which methods and first results were previously published (parlato, icm ). patients and methods: patients were prospectively included at the time of sepsis criteria, ( %) of whom with a secondary confirmed infection. community acquired pneumonia was causal in % of infections. saps score = points [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , age = years , male sex = %. patients were followed for more than days, in whom usual icu clinical and biological parameters were collected, as well as plasma biomarkers and leucocyte associated rnas. patients were clinically classified according to their acute severity (sofa score, serum lactate), confirmed initial infection, outcome (secondary infection occurrence, icu survival). non-supervised principal component analysis of the maximal values of biomarkers assessed on first days of sepsis, and varimax rotation technique of the selected components using sas software. results: patients, med sofa day = pts, med serum lactates day = . meq/l, bacterial infection = ( %), enterobacteriaceae infection = ( %), vap and/or bacteremia after day = ( %), alive at icu d/c = ( %). five components explain % of the variance of the biomarkers. the first component ( % of the variance) was not linked to the clinical predetermined phenotypes. the second component ( % of the variance) was principally made of hla-dr rna, cd rna and cx cr rna, and linked to a lower initial severity (r = − . , p = . ), a less frequent confirmation of initial infection (p = . ), a lower occurrence of pneumonia or bacteremia (p = . ) or death (p = . ). conclusion: in our cohort, using non supervised analysis, we could separate a biomarker association linked to lower initial severity, lower rate of a bacterial cause to sepsis, and better outcome. the markers found are among those which are regularly considered as describers of the peripheral alteration of the immune system observed during sepsis (pachot, ccm ; friggeri, cc ; peronnet icm ) . compliance with ethics regulations: yes. ( ) compared a standard of care to a procalcitonin (pct) oriented use of antimicrobials for sepsis in icus. serial blood samples were biobanked in / icus ( / patients enrolled for pro-adrenomedullin (proadm) and pct concentrations). patients and methods: the aim of the study was to evaluate the respective impact of serial pct and proadm measurements in predicting relapse or superinfection and death on day *. relapse was defined as the growth of one or more of the initial causative bacterial strains (i.e., same genus, species) from a second sample taken from the same infection site at h or more after stopping of antibiotics, combined with clinical signs or symptoms of infection. superinfection was defined as the isolation from the same or another site of one or more pathogens different from that identified during the first infectious episode, together with clinical signs or symptoms of infection [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] points at amission, medical admission: ( %), immunocompromised: ( %), on mechanical ventilation ( %), pct and proadm at inclusion were [ . - . ] ng/ml and . [ . - . ] nm/l respectively. ( %) patients developed a first episode of recurrence or supereinfection after a median delay of days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and ( %) died before d . the hr maximization process proposed an optimal cut point of ng/ml for pct and nm/l for pro adm to predict d death. in the multivariate cox model, both pct and proadm were associated with death but not with relapse or superinfection (table ) . conclusion: conclusion: both serial measurements of pct and proadm are independent predictors of death in patients treated for sepsis in icu. our study confirmed the use of nm/l as a good prognosis cut point for proadm. . compliance with ethics regulations: yes. rationale: the performance of serum ( - )-β-d-glucan (bdg) and its evolution to predict the occurrence of invasive fungal infection (ifi) in a high risk non immunocompromized population remains to be determined ( ). in a post hoc analysis of the empiricus randomized clinical trial ( ), we aimed to assess the prognostic value of repeated measures of bdg on the occurrence of invasive fungal infections. patients and methods: non-neutropenic, non-transplanted, critically ill patients with icu-acquired sepsis, multiple candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between july and february in french icus were included. bdg were collected in icu at day , , , and after inclusion. a value time of more than pg/ ml, pg/ml and an increase by more than % from the previous measurement (threshold of measurement error) were assessed at baseline and overtime. for that purpose, we conducted cause specific hazard models with death as a competing risk. we also planned subgroup analyses on the placebo and the micafungin groups. cumulative risk (cumrisk) of ifi at day were derived from models. [ . ; . ] ). neither a bdg > pg/ml, nor an increase by % of bdg over time were associated with the occurrence of ifi. similar results were found in the placebo subgroup. conclusion: among high risk patients, a first measurement of bdg over pg/ml was highly associated with the occurrence of ifi. neither a cut-off of pg/ml, nor repeated measurements of bdg over time seemed to be useful to predict the occurrence of ifi. the cumulative risk of ifi in the placebo group if bdg > pg/ml is . % questioning about the potential interest of empirical therapy in this subgroup. compliance with ethics regulations: yes. rationale: since the sepsis- conference, the distinction between sepsis and septic shock is based on blood lactate value. septic shock may be encountered in the pre-hospital setting. in order to reduce the mortality, the precocity of treatments implementation has been emphasized, particularly early antibiotic administration. prior antibiotic administration, and blood culture drawing must be performed. the aim of this survey was to clarify the capabilities of french prehospital emergency service (pems) to measure blood lactate and to draw blood culture prior to hospital admission for septic shock. patients and methods: we performed an electronic survey of auto-questions addressed to the deputy chair of the french pems in . results: sixty pems ( %) participated in the survey. twenty-five percent are able to measure blood lactate and % are able to draw blood culture in the prehospital setting. ninety-five percent declared lactate measurement is helpful in assessing severity. ninety percent claimed that the lactate value influences the hospital facility, emergency department vs. intensive care unit. twenty-eight percent believe that the impossibility to draw blood culture precludes prehospital antibiotic administration. sixty-three percent estimate that a protocol for septic shock management would be beneficial. conclusion: few french pems are able to measure lactate and draw blood culture in the prehospital setting. the impact of blood lactate measurement and blood culture drawing by pems on septic shock outcome requires further studies. compliance with ethics regulations: yes. rationale: head injury is a common cause of morbidity and mortality in the first four decades of life, accounting for approximately , annual hospital admissions in the united kingdom. the majority of patients recover without intervention, however some may develop a long-term disability or even die. the early detection of pathology is therefore absolutely critical in determining patients' prognosis, helping to provide appropriate timely management. the national institute for health and care excellence (nice) adult head injury guidelines, recommend that head injuries with specific risk factors should have a ct scan within h of risk factors being identified. furthermore the provisional report should be made available within h of the scan. this audit assessed the compliance of staff to the nice adult head injury guidelines. patients and methods: the previous adult ct head scans, requested due to head injury, from the emergency department (ed) at london north west healthcare nhs trust were analysed for compliance to the nice guidelines. the standards measured were: ( ) time from request of scan to completion of scan should be within h; ( ) time from completion of scan to publication of provisional report should be within h. the locally agreed target for both standards was %. results: on review of the ct scans, ( %) were completed within h of request. from the scans ( %) not completed within the hour, were due to porter unavailability, due to an uncooperative patient and the remaining reasons were not clear from documentation. following completion of the scan, scans ( %) were provisionally reported within h. conclusion: this study highlighted a good compliance by hospital staff in ensuring patients with head injuries are managed appropriately, following detection of risk factors indicating a ct head scan. having said that, the locally agreed targets were just short of being met. one factor resulting in delayed scans was porter availability. an intervention recently introduced is the use of the "e-portering" application, which will endeavour to save time for referrers requesting porters and allow patient tracking. it is also worth educating porters, via email bulletins, on the importance of priority scans, such as ct head following injury. furthermore, the findings of the audit were relayed to the radiology department to help improve reporting times and to the ed to re-emphasize prompt requesting of ct head scans when clinically indicated. compliance with ethics regulations: yes. rationale: continuous insufflation of oxygen (cio) performed with specific endotracheal tube during cardiopulmonary resuscitation (cpr) is as effective as intermittent ventilation on endotracheal tube. experimental data suggest that cio improves the efficacy of external cardiac massage and reduces gastric dilatation. as endotracheal intubation is a cause of cpr interruption and requires skilled staff, a specific device has been developed to perform cio without intubation. this device has been implemented progressively in our fire department since . we evaluated this practice. patients and methods: longitudinal study comparing the patients with out-of-hospital cardiac arrest managed by our fire department with cio or bag-valve ventilation between january and april . patients who received mechanical chest compression were excluded. the main outcome was hospital survival. secondary outcomes were the return of spontaneous circulation (rosc) and cpr quality. univariate and multivariate analysis was performed in the whole cohort and in the sub-groups of patient with shockable and non-shockable rhythms to take into account factors associated with survival (shockable rhythm, witness, age). results: among the patients included, have been ventilated with cio and with valve-bag. the mortality was similar in the two groups (cio: . % valve-bag: . % p . ). mortality and rosc were not associated with cio in the multivariate analysis (odds ratio or . %-confidence interval ci [ . - . ] and . [ . - . ], respectively). cpr quality was better with cio than with valve-bag regarding cpr fraction (ratio of duration of chest compressions on total duration of cpr, versus % p < . ) and adequacy to the guidelines of the rhythm and depth of chest compressions ( % vs % p < . and % vs % p < . , respectively). in both subgroups of patients, cpr quality was still better with cio than with valve-bag. in the subgroup of patients with shockable rhythm, univariate analysis showed a lower mortality among the patients with cio than among the patients with valve-bag ( . % vs . % p < . ) but this difference was not confirmed by the multivariate analysis (or . ci [ . - . ], p . ). conclusion: cio without intubation is associated with an improvement of cpr quality but neither with mortality nor return of spontaneous circulation in case of out-of-hospital cardiac arrest. compliance with ethics regulations: yes. rationale: cardiovascular accidents are a leading cause of death. a cardiopulmonary resuscitation (cpr) of quality has well shown that can reduce the mortality; despite this, survival rate has not changed significantly during last years. the aim of this study is to test a new wearable glove to provide lay people with instructions during out-ofhospital cpr. patients and methods: we performed a blinded, controlled trial on an electronic mannequin ambuman to test the performance of adult volunteers, non-healthcare professionals performing a simulated cpr both, without and with glove, following the glove instructions. the group without glove, also called "no-glove" is intended as control group. each compression performed on the electronic mannequin ambuman was recorded by a connected laptop computer, drawing a depth frequency curve over the time. primary outcome was to compare the accuracy of the two simulated cpr sessions in terms of depth and frequency of chest compressions performed by the same lay volunteers. secondary outcome was to compare the decay of performance and percentage of time in which the candidate performed accurate cpr. finally, the participants were asked if the glove was useful for cpr maneuvers. the difference between the two groups in regard to change in chest compression depth over time due to fatigue, defined as decay were also analyzed. results: chest compressions were included: in control group, in glove group (table ) . mean depth of compression in the control group was . mm versus . mm in the glove-group (p = . ). compressions with an appropriate depth were not statistically different ( . % vs . %, p = . ). mean frequency of compressions in the group with glove was . rpm vs . rpm in the control group (p < . ). the percentage of compression cycles with an appropriate rate (> rpm) was . % in the group with the glove versus % in the control group, with an observed difference of . % between the two groups, which was statistically significant (p < . ,ci = %). a mean reduction over time of compressions depth of . mm (sd . ) was observed in the control group versus a mean reduction of . mm in the group wearing the glove (sd . ), but this mean difference in the decay of compressions delivery was not statistically significant (f-ratio = . , ss = . , df = , ms = . , p = . ). conclusion: the visual and acoustic feedbacks provided by the device were useful in dictating the correct rhythm for non-healthcare professionals, translating in a significantly more accurate cpr. compliance with ethics regulations: yes. rationale: neuroprognostication after cardiac arrest (ca) is a crucial issue and current guidelines recommend delayed multimodal approach. we aimed to describe reasons for death in a prospective cohort of ca patients and evaluate the diagnostic accuracy of early combined neurological prognostication tools such as automated pupillometry (ap), continuous amplitude electroencephalography (aeeg) and cardiac arrest hospital prognosis (cahp) score performed h after return of spontaneous circulation (rosc). we set up a monocentric prospective cohort of adult ca patients admitted in icu after sustained rosc and collected data according to utstein style recommendations. reasons for death were described under recently proposed classification: withdrawal of life-sustaining therapies (wlst) for neurological reasons, wlst due to comorbidities, refractory shock or recurrence of sudden ca or respiratory failure. for patients who kept abnormal neurologic state after rosc with glasgow coma scale < , we analysed accuracy of early neuroprognostication tools (ap, aeeg and cahp score) to predict poor neurological outcome, i.e. cerebral performance category (cpc) > at hospital discharge. results: patients were admitted after sustained rosc from ca during the period ( . . to . . ). in-hospital mortality was %. neurological wlst was the first reason for death ( %). exhaustive early neuroprognostication with ap, aeeg and cahp score was available for patients. among them, poor neurological outcome at hospital discharge (cpc > ) was observed for patients ( % (fig. ) . this strategy would falsely misclassificate % of patients in a good neurologic outcome category. other survivors ( %) should then be investigated with further classical delayed neuroprognostication tools. compliance with ethics regulations: yes. rationale: management delay is one of the determining factors in the assessment of emergency department quality of care. asking for a specialized advice seems to increase the time of delay. our study aimed at measuring the delays in obtaining specialized advice and identify their major causes. patients and methods: we conducted a prospective study over the period of month. we included all adult patients presenting to the emergency department who required specialized advice. data of all patients was collected. waiting times and influencing factors were studied. results: a total of patients were included. the main reason for calling for a specialized advice was to ask for a department transfer in % of cases. the time of the day when specialized advice was solicited (n (%)): in the morning ( ); in the afternoon ( ); in the evening ( ). the main solicited specialties were (n (%)): visceral surgery ( ), trauma medicine ( ), cardiology ( ), urology ( ), and pulmonology ( ). the average waiting time between calling for and getting the specialized advice was ± min. seventy-five percent of the specialized advice was obtained within h. the causes of the delay were (n (%)): physician busy in the operating room ( ), unreachable physician ( ), physician in the outpatient clinics ( ). the impact of the waiting time was (n (%)): conflict ( ), worsening patient state ( ). the average time between calling for the specialized advice and reaching a management decision was ± min. conclusion: the increasing length of stay of patients in the ed is strongly correlated to the delay in obtaining specialized advice. the implementation of a strategy to reduce the waiting time is necessary to avoid overcrowding the emergency departments and provide optimal care. compliance with ethics regulations: yes. rationale: hypnoanalgesia has been used since few years to reduce icu-patients physical and psychological discomfort during invasive procedures. however, feasibility of overall well-being management of intubated patients with hypnosis has not been described. patients and methods: we report here the hypnotic accompaniment of a -year old patient without significant medical history hospitalized in our icu for a severe gbs during months. the gbs was diagnosed by electrophysiological study and immunologic markers. patient had nearly complete paralysis of all extremities, but no facial or bulbar muscles. he received mechanical ventilation during days, including weaning time. tracheotomy was performed at day . sedative drugs were stopped days after intubation. hypnosis sessions were startedvery early after intubation by one of our trained intensivist. eight hypnotic sessions of hypnoanalgesia or hypnotherapy were performed after approval of the patient and his parents. time distribution is reported in fig. . first and second sessions were performed in order to induce relaxation and reduce anxiety. following sessions were dedicated to: ) decrease pain intensity (initially neuropathic, then induced by physiotherapy), ) attenuate the negative perception of paralysis, ) reduce the discomfort of tracheotomy ) promote the belief in healing ) facilitate swallowing exercises. furthermore the patient was quickly trained to use self-hypnosis in order to dissociate him from pain, anxiety and icu pollutions. results: feasibility of hypnosis was judged satisfactory by the operating physician, despite mechanical ventilation. after extubation, final debriefing with the patient indicates that the most efficient sessions were those focused on anxiety disorders (using the suggestion of a safe place) and suggestions of mobility (using a mangas metaphor). the patient reported very positive perception of hypnosis use. he explained that self-hypnosis was effective to reduce many discomfort. he used it frequently (generally twice a day) for a puff of anxiety or before enoxaparin injection. our observation suggests that hypnosis seems feasible in icu-awake patients and may be an interesting way to improve their icu lived experience in combination with validated measures. further investigations are needed to evaluate its effects on post-traumaticstress disorder. compliance with ethics regulations: yes. rationale: there is little medical reference for hypnosis in the intensive care field. closed specialties such as anesthesia, emergency medicine can help and refer to hypnosis for certain technical procedures. objective: to propose landmarks for a successful implementation of hypnosis by intensivists within the intensive care unit. patients and methods: this monocentric prospective observational study was performed from february to june in the -bed medical icu of brest university hospital. collected data were: characteristics of patients and hypnosis sessions performed, demographic data, physiological parameters (heart and respiratory rates) and objective and subjective evaluation of hypnosis sessions quality. results: patients were included (mean age . ± years, saps ii . ± points). hypnosis sessions were performed, of which / under mechanical ventilation. patterns of hypnosis sessions were: anxiety/comfort ( %), during a technical procedure ( %): toe, cvc placement, thoracic drainage, upper digestive or bronchial endoscopy), initiation of noninvasive ventilation or before intubation. most of time, the hypnotic trance was permitted by formal hypnosis techniques with travel and nature themes suggestion. efficacy was qualitatively assessed and rated as "total effectiveness" for % of sessions. qualitative evaluation by hypnotherapist, technical operator and observers was respectively . ± . , . ± . and ± / . heart rate decreased from ± to ± bpm and respiratory rate/min decreased from ± to . ± rpm during sessions. discussion: after a meeting, the healthcare team carried out a brainstorming to propose hypnosis in our unit. several difficulties were observed to explain implementation failures such as: finding competent patient, respiratory assistance, difficult communication, noisy environment, many nursing care, unexpected emergencies, etc.…). this experience allowed writing a vademecum to perform hypnosis in intensive care. our aims are to get more trained caregivers and to integrate hypnosis during our postresuscitation consultation, especially for post-traumatic stress. conclusion: hypnotic tools can facilitate technical procedures and improve patients' and caregivers' quality of life within the icu. compliance with ethics regulations: yes. effect of a musical intervention during central venous catheterization in an intensive care unit: the music cat prospective randomized pilot study sophie jacquier, brice sauvage, gregoire muller, thierry boulain, mai-anh nay chr, orléans, france correspondence: sophie jacquier (sophie.jacquier@chr-orleans.fr) ann. intensive care , (suppl ):f- rationale: evaluate the effect of a musical intervention on patient anxiety during a central venous access or a dialysis catheter implantation in an intensive care unit. patients and methods: the music cat study was a prospective, single-centre, controlled, open-label, two-arm randomized trial, conducted from february to february . central venous catheterization with musical intervention was compared to standard care, i.e., the usual procedure of central venous catheterization without listening to music. eligible patients had to be able to hear, understand explanations and consent. randomisation was stratified according to ventilation type (mechanical ventilation or not) and catheter site (superior vena cava or femoral vein). the music care ® (paris, france) application was used to make the patients listen to music through headphones. each patient chose his/her musical topic on a digital tablet, just before the catheterization. the primary outcome was the change in anxiety visual analogic scale (vas) between the beginning and the end of the catheterization procedure (t -tf anxiety vas). secondary outcomes included the patient's pain vas at the end of the procedure (tf pain vas). results: patients were included in the standard care group versus in the musical intervention group. main reasons for admission were the need of central catheter for chemotherapy ( , %), and sepsis and/or shock in both groups ( , %). catheters were inserted in the internal jugular vein in most cases ( , %) and about one-third were tunnelled in both groups. there was no between-group difference regarding median t -tf anxiety vas: [iqr:− to ] in the standard care group versus − [− to ] in the music intervention group (p = . ) (fig. ) , with no significant interaction between the variables of stratification or the operator experience and the intervention. the median tf pain vas was not statistically different between groups: [ to . ] in standard care group and [ to ] in music intervention group (p = . ), with no significant interaction between the variables of stratification or the operator experience and the intervention. conclusion: in this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared to usual care. as the study may have been underpowered, larger size trials are needed. compliance with ethics regulations: yes. rationale: sleep is markedly altered in icu-patients under mechanical ventilation and may be due to noise, light, patient-care activities, patient-ventilator asynchronies, or the result of acute brain dysfunction induced by sedative drugs. to our knowledge, sleep has never been studied at icu admission before any sedation. our study aimed at assessing sleep quality of non-intubated sedation-free patients admitted to icu for acute respiratory failure. patients and methods: observational study performed in a single centre of a teaching hospital. patients admitted to icu for acute respiratory failure (respiratory rate ≥ breaths/min and pao / fio < mm hg under high-flow nasal oxygen) could be enrolled. patients with hypercapnia, central nervous disease, intubated early after admission and those with a do-not-intubate order were excluded. sleep was evaluated by complete polysomnography (psg) that started in the afternoon following admission and was continuously performed until the next morning. results: over a -year period patients were screened and patients were included. among them, patients were excluded for the following reasons: patient was intubated shortly after psg initiation, psg was lost, and eeg recordings ( %) were stopped before midnight (electrodes turned off or loss of signal). therefore, patients in whom psg was complete during the nocturnal period were retained in the analysis ( rationale: convulsive status epilepticus (cse) is a common neurological emergency associated with high mortality and morbidity rates. there are strong experimental data suggesting a potential impact of secondary brain insults (sbi) on outcome after cse. however, there is no clinical proof to support this hypothesis. our objective was to evaluate the association between sbi (mean arterial blood pressure, arterial partial pressure of carbon dioxide, arterial partial pressure of oxygen, temperature, natremia, and glycemia) at day and neurological outcomes days after cse. patients and methods: this was a post hoc analysis of the hyber-natus multicenter open-label clinical trial randomized critically ill patients with cse requiring mechanical ventilation to either therapeutic hypothermia ( - °c for h) plus standard care or standard care alone. patients still alive at day after inclusion were enrolled from march to january in french medico-surgical icus. the primary outcome was favourable outcome days after cse defined as a glasgow outcome scale score of . results: median age was of years . a previous history of epilepsy was noted in ( %) patients. most episodes ( / , %) occurred out-of-hospital, and ( %) were witnessed from their onset. cse was refractory in ( %) patients and total seizure duration was min ( - ). a favorable -day outcome occurred in ( %) patients. maximal glycemia value and hyperglycemia > . mmol/l at day were the only sbi variables associated with outcome in univariate analysis. by multivariate analysis, age > years (or, . ; % ic, . - . ; p = . ), refractory cse (or, . ; % ic, . - . ; p = . ), and primary brain insult (or, . ; % ic, . - . ; p = . ) were associated with an increased risk of poor outcome, and a bystander-witnessed onset of cse (or, . ; % ic, . - . ; p = . ) was associated with a decreased risk of poor outcome. conclusion: in our population, secondary brain insults were not associated with outcome in critically ill patients with convulsive status epilepticus; whereas age, bystander-witnessed onset of status epilepticus, refractory status epilepticus and primary brain insult were identified as strong predictors of -day functional impairment. further studies are warranted to confirm our findings. compliance with ethics regulations: yes. rationale: acute stroke (as) is a leading cause of morbidity and mortality worldwide. however, data on the prognosis andfunctional outcome of patients with as requiring icu management is limited. our purpose was to identify factors associated with good outcome (defined by a modified rankin score (mrs) of - ) months after icu admission. patients and methods: retrospective cohort of patients admitted to the medical icu of a university-affiliated hospital between january and december and coded for acute stroke using the icd- criteria. patients with traumatic stroke and isolated subarachnoid hemorrhage were excluded. results: we identified patients. median age was [ . - ] years and ( . %) were males. main reasons for icu admission were coma ( %), hemodynamic instability ( . %), acute respiratory failure ( %), and cardiac arrest ( . %). glasgow coma score at icu admission was [ ] [ ] [ ] [ ] [ ] [ ] [ ] and points. types of stroke were hemorrhagic in ( . %) patients and ischemic in ( . %). mechanical ventilation was required in patients ( . %). seizures occurred in . % of the patients and convulsive status epilepticus in . %. pneumonia was diagnosed in ( . %) patients (aspiration pneumonia n = , ventilator associated pneumonia n = ). thrombolysis or thromboaspiration were performed in ( %) patients with ischemic stroke. surgical evacuation of expanding hematoma was performed in ( . %) patients, ( . %) had craniectomy, and ( . %) had external shunt for hydrocephalus. icu and hospital mortality were . % and %, respectively. six months after icu admission, ( . %) patients had a good outcome (mrs - ), ( . %) had significant disability (mrs - ), and ( . %) were deceased (lost follow-up n = , . %). on multivariable analysis, age (or . per year ( . - . ), p = . ), saps (or . per point ( . - . ), p = . ), and hemorrhagic stroke (or . ( . - . ), p = . ) reduced the likelihood of good outcome (mrs - ) months after icu admission. conclusion: in our study, prognosis of acute stroke requiring icu admission was poor and a good functional outcome occurred in less than % of the patients at months. age, severity at icu admission, and type of stroke predicted outcome. compliance with ethics regulations: yes. rationale: in intensive care units, severe spontaneous hemorrhagic brain injuries have a poor prognosis for mortality and functional outcomes. affected patients face particular ethical issues regarding the difficulty of anticipating their eventual recovery. in this context, prognostic scores can help clinicians in patients/relatives counseling and therapeutic decisions. the previous reviews pointed out many prognostic tools for intracranial hemorrhage and subarachnoid hemorrhage but did not focus on injuries explicitly severe nor assessed the methodological limitations of the models. our systematic review aimed to assess methodologically prognostic tools for functional outcomes in severe spontaneous haemorrhagic brain, with particular attention to their clinical utilities. patients and methods: following prisma recommendations, we queried medline, embase, web of science, and the cochrane by february , . we included multivariate prognostic models explicitly developed or validated on adults with severe intracranial or subarachnoid haemorrhage. we evaluated the articles following the charms recommendations (checklist for critical appraisal and data extraction for systematic reviews of prediction modelling studies) and the tri-pod statements (transparent reporting of a multivariable prediction model for individual prognosis. results: our review confirmed the multiple publications of prognostic scores, as we found articles aiming to develop or validate prognostic tools. relying on guidelines, we discarded articles due to the lack of prognostic capacities, validation, or predictor selection. articles developed and validated a prognostic tool and externally validated existing models (fig. ) . no score was of good methodological quality in intracranial hemorrhage. we highlighted two prognostic scores in subarachnoid hemorrhages: the sahit predicting unfavorable outcome or mortality at months and the fresh predicting unfavorable outcome at months. conclusion: although prognostic studies on haemorrhagic brain injuries abound in the literature, they generally lack of methodological robustness or show incomplete reporting. with the numerous published scores, we believe that it is time to stop developing new scores. ongoing validation, recalibration, and impact studies would keep improving existing good tools. the use of "patient-centered" approaches could also enhance them, and be more appropriate to inform patients and families about their long-term potential recovery. these considerations should drive future research in the modern era of neurocritical care prognosis. compliance with ethics regulations: na. rationale: respiratory pattern analysis by a visual examination is an important part of clinical assessment but is dependent on caregiver expertise and is subjective. furthermore, there is no easy medical device used in picu to measure tidal volume (vt) and minute ventilation (mv) in spontaneous breathing patients. the clinical research unit in critical care of chusj and ets have developed a non-invasive computerized d video analyzing system (retract system) to detect and perform a video analysis of respiratory status in children. the aim of this study is to test the reliability of the retract system to monitor respiratory distress in critically ill children. the retract system is detailed in reference . in summary, cameras reproduce in d the thorax and abdomen of a subject. the respiratory status (respiratory rate (rr), tidal volume (vt), minute ventilation (mv)) assessed by the retract system was compared on a bench test (high-fidelity mannequin) and in critically ill children, to the ventilator measurements and clinician expert evaluation (gold standard). bland-altman plots were used for comparison. results: we observed a significant agreement, on mannequin, between retract system and gold standard method in estimating vt, rr and mv, i.e. % of the paired differences were within the limits of agreement in bland-altman plots, as illustrated in fig. . in critically ill children (n = ), the correlation between the pairs of measures was also high (r > . , p < . ) and thecoefficient of determination with a high fit ( . < r < . , p < . ). for good correlation, the retract system needed to have a visual access to thorax and abdomen in a quiet subject. the retract system measurements of vt, rr and mv for respiratory distress monitoring in patients seems reliable. more testing are required to validate this method in usual practice and to develop the retractions signs video analysis. compliance with ethics regulations: yes. rationale: severe bronchiolitis requires hospitalization in paediatric intensive care unit (picu). non-invasive ventilation (niv) has been demonstrated to treat them since twenty years, its use is well defined but there is no consensus for the weaning. this study evaluated the application of a nurse-driven niv weaning protocol in hospitalized infants with severe bronchiolitis and verified its safety. this was a retrospective monocentric study in a picu of robert debré hospital-paris, france. in the epidemic period of bronchiolitis between and , all patients under one year old with severe bronchiolitis and requiring niv were included. two groups were compared: one group using the nurse-driven niv weaning protocol and one group without using this protocol. occurrences of complications, duration of ventilatory support and length of stay (los) in picu and total los were compared. results: patients were included in the study, in the no-protocol group, and in the protocol group. the nurse-driven protocol was using at the rate of % (n = / in the protocol group (p = . ). picu los were . days [ ] [ ] [ ] in the no-protocol group versus days [ - . ] in the protocol group (p = . ), hospital los was days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the no-protocol group versus days [ ] [ ] [ ] [ ] [ ] [ ] in the protocol group (p = . ) (fig. ) . the use of this first nurse-driven niv weaning protocol was feasible and simple with a very good application rate. its utilization was safe. the occurrence of complications did not increase by the use of this protocol. it would allow an optimal niv weaning without prolonging the ventilatory support duration nor picu los or hospital los. the professional practices appeared to be coordinated and the nurses appeared to be more autonomous. compliance with ethics regulations: yes. no-protocol and protocol groups comparison: cpap duration ( ), ventilatory support duration ( ), picu los ( ), hospital los ( ) rationale: first-line management of severe acute bronchiolitis in infants is mainly based on non-invasive ventilation (niv) and high-flow nasal cannula (hfnc) therapy. however, pediatric data regarding weaning from niv/hfnc are lacking. this study aims to identify the weaning practices from niv/hfnc in children with severe bronchiolitis. the weaniv-survey is a cross-sectional survey. a questionnaire was sent to french-speaking physicians with key roles in pediatric intensive care units. results: a total of % ( / ) of french university hospital were represented in the study. only % of pediatric centers used a protocol for weaning from niv/hfnc and nurses were considered as key-actors of the weaning process for half of participants. continuous positive airway pressure (cpap) was the mode of ventilation mainly used as the first-line therapy in clinical practice. the main criteriaconsidered toinitiate weaning process were: noor slight respiratory distress, a fio < %, a respiratory rate < /min and no significant apnea. three strategies to discontinue niv/hfnc were identified: /gradual decrease of ventilatory parameters (pressure or flow), /abrupt discontinuation and /gradual increase in off-ventilation time. abrupt weaning strategy was the most commonly used, no matter the mode of ventilation. a significant level of respiratory distress, the presence of apneas, an increase in oxygen requirement, and a respiratory rate > / min were identified as weaning failure criteria by most pediatric intensive care physicians. conclusion: in most centers, the weaning process does not follow any protocol. abrupt weaning seems to be commonly used as weaning strategy in children with severe bronchiolitis supported by niv/hfnc. based on the study findings, we suggest that criteria for weaning initiation and for weaning failure must be defined and weaning protocols generated. compliance with ethics regulations: yes. complications secondary to prone positioning occured for patients ( . %). conclusion: this first study, which evaluate prone positioning efficacy in severe p-ards shows evidence that prone positioning improves oxygenation parameters and survival rate. these results highlight the necessity to develop a multicentric prospective randomized study to confirm these conclusions. compliance with ethics regulations: yes. ( vs ) and vasoactive-inotropic score (vis) ( vs ) were significantly higher in the non-survivor group. cannulation was veno-venous ( %) or veno-arterial ( %) and patients ( %) were finally not initiated on ecmo. we observed an increase of patients cannulated in our picu over time (fig. ). there was no significant difference in mortality between patients transported on ecmo after cannulation in our picu and those who were transported to be cannulated in a referral ecmo center. the median time between the decision and the cannulation was . h and the median time taken in charge by picu transport team was approximately h. these periods were not significantly different between cannulation on site or in an ecmo center and between survivors and not-survivors. conclusion: in our study, multiple organ dysfunction, particularly hematologic and acuterenal failures, seems to be a risk factor of mortality. the delay between decision and management is similar whatever the cannulation site. specific ecmo mobile team and picu transport team seem to be essential, fast and trained to transfer these patients. it would be interesting to compare our cohort with children requiring ecmo already hospitalized in a referral ecmo center. compliance with ethics regulations: yes. rationale: life expectancy in patients with metastatic breast cancer (mbc) has substantially improved over the last decade. life threatening complications result from advanced diseases, infection and treatment-related toxicity. only few studies have assessed outcomes in this setting. we performed a hospital-wide study to investigate how icu resources are needed in patients with mbc. patients and methods: all patients with mbc managed at our hospital between and were retrospectively included. the primary outcome was overall survival (os). factors associated with icu mortality were identified using a multivariable cox proportional hazard model with sensitivity analysis. results are expressed as median [interquartile ranges] unless stated otherwise. results: among the patients managed at our hospital, ( %, including male) were admitted to the icu ( [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] patients per year). age was [ - ] years. patients were receiving their nd [ st- rd] line of treatment and had [ ] [ ] metastatic sites. sofa score at admission was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . main reason for icu admission was sepsis (n = , %), acute respiratory failure (n = , %), coma (n = , %) and metabolic disorder (n = , %). invasive mechanical ventilation was required for patients ( %) and renal replacement therapy for ( %). sixteen ( %) patients died in icu. following icu discharge, median os was . months ( % ci [ . - . ]) and / ( . %) patients died within months. an antineoplastic treatment was resumed for / ( %) patients alive after icu discharge. factors independently associated with mortality were performance status ≥ (hr . , % ic [ . - . ] ) and sofa score at day (hr . per point, % ic [ . - . ] ). after sensitivity analysis, the number of treatment lines at icu admission was not associated with mortality. conclusion: icu admission is required in the course of the mbc disease for % of the patients. determinants of short term outcomes rely on performance status and disease severity but not on the characteristics of the underlying disease. ongoing analyses will assess whether icu survivors reach life expectancy of patients never admitted to the icu. compliance with ethics regulations: yes. hubert gheerbrant , jean-françois timsit , nicolas terzi , stephane ruckly , mathieu laramas , matteo giaj levra , emmanuelle jacquet , loic falque , denis moro-sibilot , anne-claire toffart chu grenoble alpes, grenoble, france; aphp, paris, france; outcom-erea, bobigny, france correspondence: hubert gheerbrant (hgheerbrant@chu-grenoble.fr) ann. intensive care , (suppl ):p- rationale: the prognosis of critically ill cancer patients admitted in intensive care unit (icu), remains an issue. our objective was to assess the factors associated with -and -month survival of icu cancer survivors. patients and methods: based on the french outcomerea ™ database, we included solid cancer patients discharged alive, between december and november , from the medical icu of the university hospital in grenoble, france. patient characteristics and outcome at and months following icu discharge were extracted from available database. results: of the cancer patients with unscheduled admissions, ( %) were discharged alive from icu. the main primary cancer sites were digestive ( %) and thoracic ( %). the -and -month mortality rates were % and %, respectively. factors independently associated with -month mortality included ecog performance status (ecog-ps) of [ ] [ ] . . - . ). interestingly, cancer chemotherapy prior to icu admission was independently associated with lower -month mortality (or, . ; % ic: . - . ). among patients with an ecog-ps - at admission, % (n = ) and % (n = ) displayed an ecog-ps - at and months, respectively. at months, ( %) patients received anticancer treatment, ( %) were given exclusive palliative care. discussion: factors associated with -month mortality are almost the same as those known to be associated with icu mortality. we highlighted that most patients recovered an ecog-ps of - at and months, in particular those with a good ecog-ps at icu admission, and could benefit from an anticancer treatment following icu discharge. conclusion: these results should be taken into account when deciding upon icu admission. it is of paramount importance to have an evaluation of both patient's general condition and anticancer treatment opportunities following icu discharge. compliance with ethics regulations: yes. rationale: the decision to urgently initiate medical anti-cancer treatment in cancer patients admitted to intensive care unit for cancerrelated organ failure is an issue. we currently lack criteria to select patients who may benefit from the treatment initiation. the purpose of our exploratory study was therefore to evaluate the characteristics of patients whose medical anti-cancer treatment is initiated in icu and to identify prognostic factors for in-hospital mortality. in these patients. patients and methods: we analyzed retrospectively, over a period of years ( / / to / / ), cancer patients over -year old admitted to our icu bordet and in whose anti-cancer medicaltreatment was initiated during in-icu stay. to identify prognostic factors for in-hospital mortality, we carried out a multivariate analysis of the factors influencing this mortality, considered as a binary. we also analyzed the long term survival of patients alive after their hospital stay (from the day of going out of hospital). results: overall, patients were included, men ( %) and women ( %), with a median age of years ( - ). of these, patients ( %) had a solid tumor and ( %) had a hematological tumor. in-icu mortality is % ( % ci - %) and in-hospital mortality % ( % ci - %). the prognostic factors for in-hospital mortality were age (mean vs in those who survived), the sofa score (median vs ), the saps ii score (mean vs ), the charlson score (mean vs. . ), the number of organ failure (mean . vs . ) and the presence of a therapeutic limitation (ntbr stated within h: % vs %). survival at year of patients who survived the hospital stay was % and median survival time was estimated to be . year ( % ci . - . ). in patients with a solid tumor, -year survival was % and % in those with a hematological tumor (p < . ). conclusion: we observed, in selected cancer patients admitted to the icu for a cancer-related complication, that the initiation of an anti-cancer medical treatment is feasible and can lead to interesting results, particularly in patients with a hematological tumor. compliance with ethics regulations: yes. rationale: considerable progress in the management of onco-hematology (oh) malignancies led to an increase in the number of patients proposed for intensive care unit (icu) admission. several guidelines offer decision models for icu transfer of these patients. we aimed to describe prognosis, adequacy of icu admission and denial in oncohematology patients. we included all oh patients proposed for icu admission in a tunisian medical icu, between january and july . from an admission proposal registry, were collected patient underlying condition, functional status, malignancy and predicted prognosis, acute critical illness and its reversibility, adequacy of icu rationale: cancer patients frequently need intensive care support for a life-threatening condition due to the underlying neoplasm or an adverse therapy-related event. however, there are poor data on their characteristics and outcomes in the intensive care setting. the aim of the present study was to describe clinical characteristics and to identify factors associated with in-icu mortality in critically ill cancer patients. patients and methods: it is a retrospective study conducted in the medical icu of farhat hached teaching hospital between january and december . all cancer patients with complete records were included. baseline characteristics, clinical parameters, severity of illness, primary tumor location and outcomes were collected. univariate and multivariate regression analyses were carried out to identify factors independently associated to poor prognosis. rationale: prognostic impact of underlying malignancy seems limited in most studies assessing outcome of critically ill cancer patients [ ] . however, only limited number of characteristics, namely disease progression status and preexisting stem cell transplantation, were usually assessed [ ] . primary objective of this study was to assess influence of hematological malignancy aggressiveness on hospital outcome. secondary objective was to assess influence hematological malignancy aggressiveness on type of infection. patients and methods: post-hoc analysis of prospective multicenter cohort performed in hospitals in france and belgium and including critically ill adults with underlying hematological malignancy admitted in icu from jan to may . a cox model was used to adjust for confounding variables then a propensity score matching on characteristics associated with underlying malignancy aggressiveness was performed. results: of the included patients, ( . %) had low grade malignancy (lg), the most frequent being myeloma (n = ), chronic lymphocytic leukemia (n = ), and myelodysplasia (n = ). patients with lg malignancy were older, underwent more frequently autologous stem cell transplantation (sct) and had less frequently altered performans status. they had more severe organ failure at icu admission (sofa score [ ] [ ] [ ] [ ] [ ] [ ] vs. [ ] [ ] [ ] [ ] [ ] [ ] , p = . ). before adjustment, mortality was % (n = ) and . % (n = ) respectively in patients with and without lg malignancy (p = . ). after adjustment for confounder using a cox model, a higher mortality was associated with nonlow grade malignancy (or . ; % ic . - . ). a propensity score then allowed a : matching upon variable associated with malignancy aggressiveness. after matching unadjusted mortality was % (n = ) in patients with lg malignancy and . % (n = ) in patients with high grade malignancy (p = . ) (figure) . in the matched cohort and after adjustment for confounder, high grade malignancies were associated with lower mortality (or . ; % ic . - . ). risk of fungal infection was unchanged by underlying malignancy before adjustment ( % vs. . % of patients with and without lg malignancy; p = . ) or after adjustment (hr . ; % ic . - . ). conclusion: despite anti-cancer advances, aggressiveness of hematological malignancies is associated with overall icu outcome. lowgrade malignancies displaying a better prognosis than non-low grade. aggressiveness of the underlying malignancy is not associated with risk of fungal infection. compliance with ethics regulations: yes. rationale: guillain-barré syndrome is the most common cause of acute flaccid paralysis and is associated with pulmonary embolism due to the mobility limitation. the aim of this study is to describe the incidence, the severity of pulmonory embolism in patients admitted to an intensive care unit (icu) for guillain-barre syndrome (gbs). patients and methods: twenty-eight adults patients with confirmed diagnosis of gbs were admitted to the icu in our university hospital center over a -year period and they were all included. prevalence, risk factors and course of vte were analyzed in icu patients with various forms and severity of gbs. results: during the study period, adult gbs patients were included. five ( . %) developped pulmonary embolism. the mean age was . ± . years and the sex ratio was . . the comparaison betewen the groups with and without pe showed that factors associated with the development of this complication were: respiratory failure requiring mecanical ventilation (p = . ), infectious complications (p < . ), blood pressure lability (p = . ), the delay of icu admission (p = . ), the delay to treatment initiation (p = . ), the sofa score (p = . ) and the presence of quadriplegia (p = . ). conclusion: pulmonary embolism is a frequent complication in patients with gbs. factors associated with this complication were: respiratory failure requiring mecanical ventilation, infectious complications, the delay of icu admission, the delay to treatment initiation, a high sofa score and the presence of quadriplegia. preventive measures in this category of patients have to be improved. rationale: acute respiratory distress syndrome (ards) is a life-threatening pathology associated with very high morbidity and mortality ( - %) in intensive care units (icu) and with even higher mortality among the severly burned patients worldwide ( à %). the aim of our study was to describe in tunisia burn patients with ards and to identify prognosis factors. patients and methods: we conducted a descriptive retrospective study between - - to - - , in burns icu, in ben arous, in tunisia. all burns who presented an ards, according to the berlin definition, during their stay in the icu, were included. when clinical or gasometric data was uncomplete, these patients were excluded. results: during the study period, patients were admitted to our burn unit including ventilated patients. fifty patients presented an ards: fifteen patients were excluded for lack of information, and patients were retained. the sex ratio was . . patients had a mean age of ± years, an average burned area of % ± %, an average unit of burn skin score (ubs score) of ± and an average sequential organ failure assessment score (sofa score) of . none of the patients had a history of cardiovascular or pulmonary diseases. the average time of onset of ards was ± days. ards was mild in case, moderate in and severe in . the etiology of ards was pulmonary in cases ( %) and extra-pulmonary in ( %). the pulmonary ards had as cause pneumonia isolated in patients, an isolated pulmonary burn in patients and a combination of pneumonia and lung burns in patients. extra-pulmonary ards were all due to sepsis and mainly to bacteremia. septic shock was associated with ards in patients ( %). the treatment was a conventional treatment based on protective ventilation, curarization and prone positioning in addition to the etiological treatment. the average length of stay in icu was days and mortality was % in these patients. conclusion: mortality from ards in burns in tunisia, is important especially in those with pulmonary burns as well as those with sepsis. the introduction of new treatments, such as extracorporeal membrane oxygenation, remains essential to improve the prognosis of burn patients. compliance with ethics regulations: yes. rationale: aspiration pneumonia (ap) is common in intensive care unit (icu). the incidence of ap among adults hospitalized with pneumonia ranges between and . %. usually one or more risk factors are identified to be involved in ap. the aim of this study was to determine the risk factors and predictors of mortality on patients with ap. patients and methods: we retrospectively included patients aged more than years and who were hospitalized in our icu for ap. patients were excluded if they had history of tuberculosis, if they have bronchiectasis or metastatic brain tumor. results: a total of patients were included. history of diabetes, hypertension, epilepsy and ischemic stroke were found respectively in . %, . %, . %, and . % of cases. the reason of icu admission were coma ( %), acute respiratory failure ( %), poisoning ( %) and cardiac arrest ( %). the incidence of acute respiratory distress syndrome (ards) was %. the most common organism isolated was staphylococcus aureus ( cases). risk factors for ap were epilepsy ( %), swallowing disorders ( %), ischemic stroke ( %), copd ( %) and degenerative neurological disease ( %). the mortality rate was . %. the median duration of mechanical ventilation was days [iqr - ]. in multivariate logistic regression analysis; saps ii score (or = . , % ic [ . - . ], p = . ) and ards (or = . , % ic [ . - . ], p = . ) were independently associated with mortality. conclusion: risk factors for aspiration pneumonia were epilepsy, swallowing disorders and ischemic stroke. ards and saps ii score were independent predictive factors of mortality. compliance with ethics regulations: yes. undetermined. the aim of this study was to evaluate the impact of hyperoxia on morbidity and mortality. patients and methods: this was a prospective study performed in the icu of abderrahmen mami hospital during a -month period. all patients admitted in icu during the study-period were included. those who didn't need oxygen therapy or in end of life stage were excluded. arterial blood gases were analyzed daily and each day with at least one value of oxygen arterial saturation (sao ) > % was considered as a day with hyperoxia. for each patient included, the number of times and days spent in hyperoxia was recorded as well as complications during the icu stay and the outcome. results: during the study-period, patients were included but only were eligible. mean age was ± years. acute on chronic respiratory failure was the most frequent reason of admission ( %). non-invasive ventilation was required for % of patients and invasive mechanical ventilation was necessary in % of cases. overall mortality was %. hyperoxia was observed in % of cases, with an average of ± times during the icu stay and ± days. a statistically significant association was observed between a long duration of hyperoxia and the occurrence of ventilator acquired pneumonia (p < - ), ventilator acquired bronchitis (p = . ), acute respiratory distress syndrome (p < - ), atelectasis (p < - ), septic shock (p < - ), rythm disorders (p = . ), reintubation (p < - ) and tracheostomy (p = . ). on multivariate analysis, independent factors of mortality were: simplified acute physiology score ii, cardiac failure, need for invasive mechanical ventilation and septic shock. hyperoxia was not independently associated with mortality. conclusion: hyperoxia is frequent in icu. it is significantly associated with icu complications but not independently associated with mortality. compliance with ethics regulations: yes. experience of the practice of prone position in patientswith acute respiratory distress syndrome in intensive care (chu oran) nabil ghomari, soumia benbernou, djebli houria faculté de medecine d'oran, oran, algeria correspondence: nabil ghomari (nabilghomari@hotmail.fr) ann. intensive care , (suppl ):p- rationale: mechanical ventilation (mv) in the prone position (pp) and low tidal volume have become recommendations with a high level of scientific evidence in recent years. the pp has been practiced for years in the chu oran emergency resuscitation service. we wanted to report the service experience in the practice of pp in patients with ards. patients and methods: retrospective study performed in patients with severe hypoxia ards with spo < % under fio > % or pao /fio < during the period march to december . results: patients received ventilation in pp. ards was secondary to thoracic trauma in % of patients, septic shock in % and aspiration pneumonitis in %. analysis of the success factors and improvement of oxygenation found that lobar ards, the delay < h and a duration of pp ≥ h were statistically significant. conclusion: the pp must be integrated into the arsenal of care of the patients in ards especially in our country where we do not have all the therapeutic options. compliance with ethics regulations: yes. julien goutay, nicolas cousin, thibault duburcq, erika parmentier-decrucq chu de lille, pôle de réanimation, hôpital salengro, lille, france correspondence: julien goutay (julien.goutay@gmail.com) ann. intensive care , (suppl ):p- rationale: in veno-venous extracorporeal membrane oxygenation (vv-ecmo) therapy, blood flow is the main determinant of arterial oxygenation and should be - ml/kg/min in adults. this flow rate is determined by several factors including the size of the inflow cannula. the impact on clinical outcomes of arterial cannula's size in veno-arterial ecmo (va-ecmo) has already been studied, and showed no difference for survival to discharge, weaning success rate and initial flow rate between a small cannula group and a larger one. our first objective was to describe the impact of inlet cannula size on the assistance flow rate in patients treated with vv-ecmo. secondary objectives were to analyze its impact on ecmo weaning, mechanical ventilation characteristics and mortality. patients and methods: we retrospectively reviewed all cases of respiratory failure treated with vv-ecmo admitted in the medical intensive care unit (icu) of lille's teaching hospital from january st, through march st, . inlet cannula size was collected and divided into two groups: the "small cannula" group had inlet cannula less than or equal to fr, while "large cannula" were larger than fr. primary endpoint was the initial flow rate according to the inlet cannula size, and its changes during the first h of assistance. secondary endpoints were the analysis of predictive factors associated with the choice of a larger inlet cannula, and the impact of its size on clinical outcomes such as successful ecmo weaning. results: patients treated with vv-ecmo were admitted in our hospital. eleven ( %) were cannulated with a large inlet device. mean initial ecmo flow rate was statistically higher in the "large cannula" group than in the "small cannula" one: . l/min (± . ) versus . (± . ) respectively, p < . . the difference was also significant during the first h of assistance. we found no difference between the two groups on clinical outcomes such as ecmo weaning time. in univariate analysis, weight was heavier in the "large cannula" group [ (± ) kg] than "small cannula" [ (± )], p < . . conclusion: ecmo initial flow rate was higher in a "large inlet cannula" group (internal diameter more than fr) compared with a "small cannula" group. we found no correlation with cannula-related haemorrhagic or thrombotic complications. inlet cannula size did not influence ecmo weaning, and duration time, but this may be a lack of statistical power. further prospective studies should confirm this results. compliance with ethics regulations: yes. rationale: burn patients are at risk of multidrug-resistant (mdr) bacterial infections with high mortality rate. therefore, monitoring the emergence of mdr pathogens in these vulnerable patients is important. this study aimed to assess digestive colonization with carbapenemase-producing gram-negative bacilli (cp-gnb) in patients admitted to the burn intensive care unit. patients and methods: our study was prospective and conducted over a one-year period (january to december ). every admitted patient was subjected to the screening. a double swab set was used to collect rectal swab specimens. one swab was used for mdr screening by disk diffusion method on selective media; the other for multiplex real-time pcr (cepheid's genexpert ® ) allowing detection of the most common carbapenemase-encoding genes (ceg) (blaoxa- , blakpc, blandm, blavim and blaimp). results: among the studied patients, ( . %) were detected positive at admission for cp-gnb by the genexpert ® carba-r assay. eleven patients, initially not colonized, acquired positive faecal carriage subsequently during their hospital stay. forty-two colonized patients ( . %) developed cp-gnb infection during their hospitalization. the ceg blandm quantitatively dominated by far with detections; either alone ( cases) or associated with other ceg ( cases). the second most frequent gene was blaoxa- . it was detected alone eight times and in association with other ceg times. forty-three patients carried blavim gene, usually in association with other ceg ( %). however, only one patient carried blakpc gene. the parallel screening by classical microbiology methods (disk diffusion on selective media) detected the presence of cp-gnb in all molecular positive samples. conclusion: our study describes the characterization of carbapenemase in burn patients and highlights their alarming spread. this emphasizes the importance of an active surveillance program by early detection of cp-gnb carriers and an isolation policy to limit the mdr infections expansion. compliance with ethics regulations: yes. rationale: invasive fungal infections are increasingly observed in the icus especially in burn units. inthe absence of simple and accessible techniques for early microbiological diagnosis, the use of antifungal treatment is increasing. little is known about the extent of the problem of antifungal prescription in burn icus. we aimed to evaluate the antifungal prescription in major burn patients. patients and methods: during the study period ( - ), all prescriptions of antifungals were analysed. analysis concerned demographics, clinical circumstances, as well as the basis of antifungal prescribing (targeted vs. empiric). among the patients admitted in this period, patients were treated with antifungals (sex ratio: . ; mean age: ± years, with low associated comorbidity). the tbsa was . % [ . - . ], ubs was [ . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . most of the patients ( . %) were transferred from another hospital structure within ± h. antifungal treatment was started at the average of the seventh day post wound injury, more often on an empiric basis. sofa score at the beginning of the treatment was ± . . lymphopenia was present in % and thrombopenia was present in %. index of colonisation was positif only in cases. the average candida score was . ± . . microbiological results were tardily collected, within weeks, in %. fungal urine infections were found in cases. candidemia and catheter-related infections were considered only in cases. the risk factors of fungal infection as described in literature were found in most of the patients including mechanical ventilation ( . %), length period of stay ( days [ . - . ]), central venous line ( %), severe sepsis or septic shock ( %), large-spectrum antibiotherapy for more than days ( %). conclusion: the management of antifungal infections in major burn patients is still challenging. antifungal prescription is based on clinical presumption. the empirical prescription reflects the lack of efficient laboratory support and late microbiological results prompting physicians to rely on clinical informations. the management of fungal infections is based on the improvement of mycological investigations. compliance with ethics regulations: na. rationale: invasive candidiasis is a widespread and alarming infection in intensive care units (icu) patients. its diagnosis is often difficult because of the lack of specificity of clinical signs and the low sensitivity of blood cultures. while the candida albicans species remain the most common cause of bloodstream infections, non-albicans are emerging. these infections are serious, associated with high mortality rate and requiring early diagnosis and appropriate treatment. in tunisia, few data are available. we aimed to determine the epidemiological profile of a series of candidemia in icu, the risk factors associated with the occurrence of candidemia and to describe the modalities of the mycological diagnosis of candidemia and their etiological profile. patients and methods: a retrospective longitudinal descriptive study conducted in the parasitology-mycology laboratory with the collaboration of the medical icu of la rabta hospital-tunis over a -year period from january , to december , . all hospitalized icu patients with at least one candida-positive blood culture were included. results: forty-three patients among hospitalized patients during the study period had at least one candidemia infection. the main risk factors for development of candidemia infection include invasive procedures, a prior use of antibiotics and parenteral nutrition. c. albicans was the most common species, detected in . % of patients. nonalbicans candida species were prominent ( . %), represented by c parapsilosis, followed by c. tropicalis and c. krusei then c. glabrata and finally c. lusitaniae. all the isolates tested were sensitive to the common antifungal agents. the mortality rate of our patients was high ( . %), and the detection of the albicans species in blood cultures was the only prognostic factor identified (or = . [ . - . ], p = . ). conclusion: candidemia in the medical icu patients is common and is associated with high mortality rate. despite the progress of biological tools, the diagnosis is difficult and needs to take into account the risk factors of the patients as well as scores based on clinical and microbiological parameters. a better identification of risk patients may help to early initiate empirical antifungal treatment. compliance with ethics regulations: yes. necrotizing soft-tissue infections in the intensive care unit: a retrospective hospital-based study kais regaieg, sabrine nakaa, arnaud mailloux, madjid boukari, johana cohen, dany goldgran-toledano groupe hospitalier intercommunal le raincy-montfermeil, montfermeil, france correspondence: kais regaieg (kais.regaieg@gmail.com) ann. intensive care , (suppl ):p- rationale: the objective of our study is to describe the epidemiological and clinical characteristics of necrotizing soft-tissue infections (nsti) and to improve therapeutic management. we conducted a retrospective observational study that included patients admitted in the intensive care unit (icu) of general hospital between september and aout with a primary or secondary diagnosis of nsti. we collected demographic and clinical data, cultured pathogens, lengths of stay, and in-icu mortality. results: during the study period, a total of patients admitted to the icu were diagnosed with nsti ( . % of the total number of patients). the mean of age was years. the sex ratio (m/w) was . . ten patients ( %) were directly admitted to the icu, others were transferred from medical or surgical wards. the mean of saps ii was . ( . ). the main indication to admission in icu was shock ( %). the most common comorbidity was diabetes ( %). the other co-morbidities associated with nsti were cardiovascular diseases ( %), obesity ( %) and carelessness ( %). the sites most commonly affected were extremities in patients ( %) and abdomen/ano-genital in patients ( %). in icu, a total of patients ( %) were mechanically ventilated [ (median duration: . days ( . )], patients ( %) were given vasopressors, and patients ( %) underwent renal-remplacement. all patients underwent one or more chirurgical intervention. patients ( %) underwent radical necrosectomy. in cases, an amputation was necessary. polymicrobian infection was seen in patients ( %). in patients ( %), we used vacuum assited closure therapy, which in patients was followed by definitive reconstruction by split skin grafts. the mortality in icu was %. the mean stay in icu was days . the mean duration of hospitalization of the patients who survived was days ( - ). on the basis of a univariate analysis, higher saps ii score and lactate levels were associated with increased mortality (p < . ). conclusion: ntsi is rare in icu but it's a life-threatening and disabling disease with a high mortality requiring a multidisciplinary management. early diagnosis and adequate treatment are necessary to improve clinical outcome and must be known by everyone. more studies are needed to estimate the interest and delay of new strategies such as negative pressure therapy. compliance with ethics regulations: yes. rationale: nosocomial infections remain a major cause of mortality and morbidity in burn patients. providing information about the main causative bacterial agents and determination of their susceptibility to antibiotics may improve empiric therapy and early detection of emerging antimicrobial resistance. the aim of our study was to investigate the species distribution and antibiotic susceptibility of isolated strains from a burn intensive care unit (icu). patients and methods: this study was performed retrospectively on all bacteriological samples taken from the burn icu at the trauma and burn center in tunisia during a seven year period (from january to december ). all isolated microorganisms were identified on the basis of standard microbiological techniques. antibiotic susceptibility testing was carried out by the agar disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. minimum inhibitory concentration of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may . results: during the study period, the most frequent identified species were pseudomonas aeruginosa ( . %), staphylococcus aureus ( %), klebsiella pneumoniae ( . %) and acinetobacter baumannii ( %). these strains have been mainly isolated from blood cultures ( %) and skin samples ( . %). pseudomonas aeruginosa resistance to ceftazidime increased from . % in to . % in and resistance to imipenem and ciprofloxacin was . % and . %, respectively. four strains were resistant to colistin. rationale: community-acquired peritonitis is a heterogeneous condition characterized by peritoneum inflammation in response to a bacteria injury. the aim of our study is to describe the epidemiological, clinical, bacteriological, etiological, therapeutic characteristics of community peritonitis, and to evaluate the prognostic factors. patients and methods: this is a retrospective descriptive and analytical study spanning three years (between january and december ) involving cases of community peritonitis, hospitalized in the surgical emergency resuscitation department p ibn rochd casablanca university hospital. our study included adult patients with community-acquired peritonitis who underwent medical and surgical management. the studied parameters are the demographic data, the clinical and paraclinical signs, the care taken and the evolution of the patients. the study showed that the mean age was . ± . years, with a sex ratio of . . patients medical history included tobacco ( . %), extra-abdominal signs [hemodynamic failure ( %), renal failure (n = , %), hematological disorders (n = , %) and respiratory disorders (n = , %)]. therapeutic management was based on perioperative resuscitation, treatment of organ failure, probabilistic antibiotic therapy and median laparotomy surgery. the main etiologies of community peritonitis were: digestive perforation ( . %), purulent effusion ( %), intestinal necrosis ( . %), cholecystitis ( . %). intraoperative bacteriological specimens yielded the following bacteriological profile: predominance of ngb ( . %) dominated by e. coli ( . %) followed by klebsiella pneumoniae and enterobacter cloacae ( . %) the mean hospital stay was . ± . days. the mortality rate was . %. conclusion: improvement in the prognosis of community-acquired peritonitis can only be achieved by constant assessment of very early diagnosis and initiation of appropriate resuscitation and antibiotic therapy associated with a complete surgery carefully codified according to guidelines. compliance with ethics regulations: yes. rationale: klebsiella pneumoniae carbapenemase (kpc)-producing bacteria are a group of emerging highly drug-resistant gram-negative bacilli causing infections associated with significant morbidity and mortality. the aim of our study is to point out the incidence of bloodstream infections (bsi) caused by kpc in icu patients, its clinical presentation and course. patients and methods: we conducted a retrospective descriptive study. all patients hospitalized in the icu of our hospital who developed bsi caused by kpc from january , to december , were included. results: during the study period, patients were included. the mean age was . ± . years ranging from to years. sex ratio (m/f) was . trauma was the major cause of hospitalization in cases ( %). the most common past medical diseases were arterial hypertension in patients ( %). length of hospital stay prior to icu admission was ± . days. at infection onset, mean saps ii was ± . , mean sofa was . ± . and mean apache ii was . ± . . during icu hospitalization, all patients required invasive mechanical ventilation during . ± . days, had a central venous catheter (cvc) and an indwelling urinary catheter in place, patients ( . %) had tracheotomy, ( %) underwent surgery, ( %) presented acute kidney failure and ( %) needed hemodialysis. before the isolation of kpc, all patients presented infections. antibiotics prescript were: colistin in patients ( %), carbapenems in patients ( %), amoxicillin/clavulanic acid in patients ( %), cephalosporins in patients ( %), fluoroquinolones in patients ( %), tigecycline in patients ( %), aminosids in patients ( %), rifampicin in patients ( %), fosfomycin in patients ( %), glycopeptides in patients ( %). the delay for kpc-bsi onset was . ± . days. the most common infection sources responsible of kpc-bsi were: cvc in patients ( %) and pneumonia in patients ( %). kpc infection was responsible of septic shock in patients ( %). resistance rates were: gentamycin ( %), amikacin ( %), colistin ( %), fosfomycin ( %) and tigecycline ( %). antibiotics used to treat kpc bloodstream infection were resumed in table . the mean length of icu stay was . ± . days. out of the included patients, patients died (the mortality rate was %). death was related to kpc infection in patients. conclusion: the high prevalence of kpc-bsi in icu patients dictates the importance of implementation of infection control measures and strict antibiotic policies. compliance with ethics regulations: not applicable. we identified episodes of nosocomial infections in patients, representing a cumulative incidence rate of . per exposed patients. the incidence density was . infections per days of hospitalization. the prevalence of pneumonia was . %, followed by urinary tract infections . %, central venous catheterization infections . %, bacteriemia . %, meningitis . % and surgical site infections . %. the incidence rate of intubation-related pneumonia was . / day of exposure. the incidence rate of bladder-related urinary tract infection was . / day of exposure. the incidence rate of positive culture of the central venous catheter was . / day of exposure. the incidence rate of bacteremia related to stay was . / day of exposure. the mortality rate was . % with a significant difference between infected and uninfected patients (p = . ). microorganisms were gram negative bacteria in % of cases. conclusion: epidemiological surveillance of healthcare-associated infections is needed to establish prevention plans. compliance with ethics regulations: not applicable. in the prehospital setting, early identification of septic shock (ss) with high risk of mortality is essential to guide hospital orientation (emergency department (ed) or intensive care unit (icu)) prior to early treatment initiation. in this context, the severity assessment is most of the time restricted to clinical tools. in this study, we describe the association between prehospital shock index (si) and mortality at day of patients with ss initially cared for in the prehospital setting by a mobile intensive care unit (micu in this study, we reported an association between prehospital si and mortality of patients with prehospital ss. a si > . is a simple tool to assess severity and to optimize prehospital triage between ed and icu of patients with ss initially cared for in the prehospital setting by a micu. the association of si with biomarkers may be helpful to improve the screening for ss and decision making of ss in the prehospital setting. compliance with ethics regulations: yes. the failure rate and complications were comparable between the groups, but the ultrasound-guided internal jugular catheter appears to be faster to insert and requires fewer punctures, so it could be an alternative to the femoral one in emergency situations. rationale: neuromyelitis optica (nmo) is a rare but severe disease. the prognosis of treated nmo attacks remains unclear. we evaluated our practice, the early evolution and the prognosis of nmo patients. patients and methods: an observational study was performed on patients with nmo attacks presenting with visual or medullar symptoms admitted for plasma exchange (pe) therapy from january to august . treatment efficiency was defined as a negative shift of the visual or motor disability score (edss). nonparametric mann-whitney and fisher exact tests were used for statistical analysis as required. results: twenty-four patients had pe sessions. characteristics of the cohort are described in table . ( . %) died from complications of nmo attacks. treatment had an effect in ( . %) patients. the shift in the ambulatory and visual edss was respectively − . + . and − . + . . the non-survivor patients had all aqp antibodies (p < . ). residual edss was higher in the non-survivor group ( . + . vs . + . , p < . ). pulse steroids were administered in ( %) patient in the non-survivor group vs ( %) patients in the survivor group (p < . ). twelve ( %) patients previously given pulse steroid therapy responded to pe. discussion: we assessed the handling of nmo attacks and identified our flaws. we concluded that pulse steroid therapy should not be withheld or replaced by lower dosage. we also need to find a way to make attacks identified by physicians earlier to shorten the delay between its onset and patient's admission in a specialized care unit. we observed that the mean improvement is modest during the early phase of our treatment. but a modest improvement in the edss can have a great impact in the patient's quality of life and even survival. conclusion: nmo attacks remain a threatening disease despite aggressive treatment. shortening the delay of treatment and ensure adequate pulse steroid therapy coupled to pe could be a way to improve the prognosis. compliance with ethics regulations: yes. rationale: acute kidney injury in trauma patients is a problem that has been little studied in the intensive care unit (icu). its occurrence has been shown to be associated with high morbidity and mortality. we aim to determine the outcome of icu trauma patients with acute kidney injury (aki), including the incidence of death in the icu, of nonreversible renal impairment and icu complications. patients and methods: this is a prospective study, conducted in the department of emergencies and icu, including trauma patients with a minimum icu stay of days. renal failure was defined based on the new kdigo classification. predictors of mortality and poor outcome were identified using univariate and then multivariate analysis. results: one hundred and fifty patients were admitted during the study period for the management of post-traumatic injuries, among which patients were included. the incidence of aki in the studied population was % ( cases) with ( %) diagnosed with stage one, ten ( %) with stage two and ten ( %) with stage three. the overall mortality of patients with post-traumatic aki was . % ( patients) with a mean icu lengh of stay (los) at ± days and of days on ventilator at ± . eight patients ( . %) needed renal replacement therapy and thirty-four had non-reversible renal impairement ( %). during icu stay, eight patients ( %) were diagnosed with pulmonary embolism. on univariate analysis, the following variables were associated to mortality in patients with post-tramatic aki including; age, hemodynamic instability on the day of diagnosis and bilirubin levels on the day of aki diagnosis. besides, according to our analysis, the use of renal replacement therapy and the non-reversibility of renal impairment during icu stay were also associated to icu mortality. among these factors, the non-reversibility of renal impairment in the icu was a predictor of mortality on multivariate analysis (p = . , or = , . in this cohort, the following variables were predictive of non-reversible renal impairment during icu stay; including age (with a best cut-off of years old), medical history of hypertension, higher iss and diuretics' administration. on multivariate analysis, the age (p = . , or = . , ci . - . ) and use of diuretics (p = . , or = , ci . - ) were associated to non-reversible aki in the icu. conclusion: our study confirms that post-traumatic aki in the icu is associated to high morbidity and mortality. the identification of outcome predictors could be valuable to guide the management of aki. compliance with ethics regulations: yes. rationale: the occurrence of acute kidney injury (aki) in trauma patients is a problem that has been little studied to date. its presence has been shown to be associated with an increased risk of morbidity and mortality in affected individuals. to determine the incidence of post-traumatic aki and identify its predictive risk factors that could be eventually prevented. patients and methods: this is a -month long prospective cohortstudy, conducted in the department of emergencies and intensive care unit (icu) of a university hospital, including trauma patients with a minimum icu stay of days. renal failure was defined based on the new kdigo classification. predictors of aki were identified using univariate and then multivariate analysis. results: one hundred thirty patients were admitted during the study period for the management of post-traumatic injuries, among which patients were included. the incidence of aki in the studied population was % ( cases) with ( %) diagnosed with stage one, ten ( %) with stage two and ten ( %) with stage three. on univariate analysis, older age and medical history of diabetes or hypertension were predictors of aki. injury assessment found traumatic brain injury (ais > ), glasgow (gcs) on admission, and the diagnosis of fat embolism to be associated to post-traumatic aki. moreover, hemodynamic instability on admission and during icu stay, shock-index on admission, the amount of fluid administered the use of vasoactive drugs, sepsis, hyperbilirubinemia, p/f ratio and acute respiratory distress syndrome (ards) were also associated to post-traumatic aki. among these factors, ards (p = . , or = , ci - ), fat embolism (p = . , or = , ci . ) without preload-dependence, and were unclassified. multivariate analysis (using variables collected prior to hypotension) identified the following variables as risk factors for the occurrence of hypotension associated with preload-dependence: preload-dependence before hypotension (odds ratio = . , p < . ), fluid removal rate by crrt (or = . per increase in sd, p < . ), and lactate levels (or = . per increase in sd, p < . ). in this single center study, preload dependence-associated hypotension was slightly more frequent than hypotension without preload dependence in icu patients undergoing crrt. testing for preload dependence to adjust fluid removal could help prevent hypotension incidence during crrt. rationale: few studies report the relation between functionnal brain alterations during and after icu stay and abnormalities of cbf displayed on tcd. using vti as hemodynamic parameter is unusual for evaluation of cbf. the purpose of this preliminary study was to compare the values of vti of healthy controls (c) versus icu (p) with usual parameters (i.e. diastolic (vd) and mean velocities (vm), resistance (ir) and pulsatility index (ip)). rationale: accurate diagnosis of the level of consciousness is a challenge and different states such as coma, vegetative state (vs) or minimally conscious state (mcs) are often confused while they convey meaningful prognostic information. this distinction rely on the coma recovery scale-revised (crs-r) gold-standard. however, this clinical scale is imperfect since unresponsive patients can exhibit genuine signs of consciousness using advance neuroimaging techniques. expanding the range of behaviors indexing consciousness at bedside is thus of decisive importance. patients and methods: we designed and proposed a new clinical sign of mcs, the habituation to auditory startle reflex (asr), based on the blink response to repeated sounds: either inhibition of the automatic asr response (extinguishable) or nohabituation (inextinguishable response). we prospectively tested this new sing in patients suffering from disorders of consciousness after severe brain injury and first compared its diagnostic performances with the current gold-standard (crs-r) using standard discrimination metrics (auc, sensitivity, specificity, likelihood ratios) and their % confidence interval. we then investigated the correlates of this new sign on two validated neuroimaging diagnostic procedures (multivariate eeg-based classification of the state of consciousness and fdg-pet metabolic index of the best preserved hemisphere) using an anova with the state of consciousness and the asr response as independent variable. rationale: although continuous electroencephalography (ceeg) is commonly recommended in neurocritical care patients, implementation of this monitoring in routine is facing the need for a specific training of professionals. we evaluated the effectiveness of a training program for the basic interpretation of ceeg to critical care staffs in a prospective multicentre study. patients and methods: after completion of a pre-test, participants (physicians and nurses) recruited in french intensive care units (icu) received a face-to-face eeg learning course, followed by additional e-learning sessions at day- (post-course), day- , day- and day- , based on training tests followed by illustrated and commented answers. each test was designed in order to evaluate knowledge and skills through correct recognition of predefined eeg sequences covering the most common normal and abnormal patterns. the primary objective was to achieve a success rate of more than % of correct answers at day- in at least % of participants. results: among participants, ( . %) completed the full training program and of these ( . %) full-training participants achieved at least % of correct answers at day- . paired comparisons between scores obtained at each evaluation demonstrated a statistically significant increase over time. at day , rates of correct answers were greater than % for all predefined usual eeg sequences, excepted for the recognition of periodic and burst-suppression patterns and reactivity, which were identified in only . % ( % ci . - . ) and . % ( . - . ) and . ( . - . ) tests, respectively. discussion: this multicentric prospective study, which evaluated a training program for the basics of electroencephalography offered to critical care teams, provides interesting information about the training process and its impact on learners according to their different characteristics. we believe that participants reflect the heterogeneity of the various use of ceeg in the critical care setting. participants came from university and non-university icus, and whereas some of them used to monitor patients with ceeg, others were in an implementation process when the last monitored neurocritical care patients with intermittent eeg. in accordance with previous studies, we focused to the entire medical and nursing icu staffs. conclusion: a -months training program aiming to teach the basic interpretation of continuous eeg in the intensive care units was associated with a significant attrition in participation over time. however, participants who received the full training program were capable to accurately recognize the vast majority of eeg patterns that are encountered in critically ill patients. compliance with ethics regulations: yes. mourad goulmane oran hospital and university center, oran, algeria correspondence: mourad goulmane (goulmane.mourad@univ-oran . dz) ann. intensive care , (suppl ):p- rationale: cerebral venous thrombosis (cvt) is a rare but very serious disease with various clinical and etiological aspects. unlike ischemic arterial accidents, epidemiological studies are limited. the aim of our work was to study the clinical, etiological and evolutionary features of cvt in the algerian population from a sample of patients. patients and methods: this is a retrospective observational study conducted in the neurology department of the chu d'oran between january and december . in a clinical context suggestive of cvt, the diagnosis of certainty was provided by brain mri coupled with mra. all subjects benefited from a complete etiological assessment. the anticoagulant treatment was based on the low molecular weight heparin relayed by the anti-vitamin k. the duration of the follow-up was months. results: the mean age was . ± . years, the sex ratio was ( f/ h), the onset was subacute in % of cases. the main early signs were headache ( . %), visual disturbances ( %), epileptic seizures ( . %) and motor deficit ( . %). thrombosis predominated in the upper sagittal sinus and lateral sinuses; parenchymal lesions were associated in / of the cases. gynecologic obstetric causes were by far the most frequent. the evolution was favorable in . % of the cases. discussion: cvt is characterized by its clinical polymorphism, its predominance in young women, and its most often favorable evolution. the causes are multiple and often intricate requiring the realization of a systematic etiological assessment even if the cause seems obvious. the treatment of choice remains early anticoagulation, based on heparinotherapy even in case of hemorrhagic softening. the characteristics of cvt in the algerian population are distinguished by a high frequency of gynecological obstetric causes. awareness campaigns for women of childbearing age are useful. compliance with ethics regulations: not applicable. rationale: the ct-dragon score was developed to predict longterm functional outcome after acute stroke in the anterior circulation treated by thrombolysis. its implementation in clinical practice is hampered by the plethora of variables included. in addition, the score has not been validated in important subgroups such as stroke patients undergoing thrombectomy. given these limitations, the current study was designed to evaluate the use of a simplified score based on machine learning, as a possible alternative. this single-centre retrospective study included patients treated for stroke, in the anterior and posterior cerebral circulation, between - and - . at days, favourable (modified rankin scale (mrs): - ) and miserable outcome (mrs: - ) were predicted by ct-dragon. machine learning selected the aim was to describe the adherence rates to gold guidelines in critically ill copd patients and to identify predictors of low adherence. patients and methods: a prospective cohort study conducted from december to april in a -bed medical intensive care unit of farhat hached hospital. all adult patients admitted for aecopd during the period of the study were included. demographic and clinical data were recorded. adherence to gold was evaluated. univariate and multivariate regression analyses were carried out to identify factors independently associated to non-adherence to gold guidelines. results: seventy-seven patients were recruited. patients' characteristics were : mean age, . ± years; male ( . %); median duration of the disease, [ - ] years; mmrc scale ≥ , ( . %); health insurance coverage rate, ( %); pulmonologist follow up, ( , %); frequent exacerbator (≥ exacerbations in the last year), ( . %); median exacerbations episodes, [ ] [ ] [ ] . long-term oxygen use and home mechanical ventilation were respectively used in ( . %) and ( . %). eight ( . %), ( . %) and ( . %) belonged to copd groups b, c and d, respectively. pharmacological treatment included: saba-ics combination, ( . %), laba-ics, ( . %), laba-lama, ( . %) and lama-laba-ics, ( . %). overall adherence to gold guidelines treatment recommendations for the different stages of copd was ( . %). two patients ( . %) were over treated and ( . %) were undertreated. inappropriate treatment rate was ( %) in gold b, ( . %) in gold c and ( . %) in gold d. univariate analysis identified two factors associated with non-adherence to gold : the absence of pulmonologist follow-up ( % vs. . %; p = . ) and the low income ( . % vs. . %; p = . ). in multivariate analysis only the lack of pulmonologist follow-up was identified as an independent risk factor associated with gold guidelines discrepancies (or, ; % ci [ . - . ]; p = . ). there is a lack of adherence to gold guideline treatment recommendations in tunisian copd patients. this may lead to severe exacerbations. discrepancies were due to the poor access of severe copd patients to an appropriate pulmonologist follow-up. compliance with ethics regulations: yes. the operating theaters concerned were: the otolaryngology block, ophthalmology, vascular and thoracic surgery, and gynecological surgery. all patients over years of age were enrolled using the clinical parameters of difficult intubation (arne score > ), which will benefit from orotracheal intubation. the main judgment criteria were: first-pass success rate, intubation time, which is defined as the time between inserting the slide into the patient's mouth and obtaining the capnography curve, the cormack-lehane score and the pogo score (percentage of opening of the glottis). statistical analysis used spss software. results: a total of patients were included. no cases of failure with this device were observed, the duration of intubation was on average . s (only cases required more than min). the cormack-lehane score and involved patients ( . %), and the pogo score greater than % involved patients ( . %). one case required the features of the simplified score. discrimination, calibration and misclassification of both models were tested. results: % had proximal anterior stroke, % proximal posterior stroke and % lacunar infarcts in either circulation. in % no thrombus was objectivated. % of patients were treated with thrombectomy, % received thrombolysis and % underwent both thrombolysis and thrombectomy. % only received anti-platelet therapy. the area under the receiver-operating-characteristic curve (auc-roc) for ct-dragon was . ( % ci . - . ) for favourable and . ( % ci . - . ) for miserable outcome. r ofct-dragon was . and . for favourable (lack of fit, p = . ) and miserable (lack of fit, p = . ) outcome respectively. misclassification rate was % for favourable and % for miserable outcome with ct-dragon. selection of predictors from the ct-dragon was done by logistic regression, bootstrap forest and decision tree analysis. nih stroke scale, pre-stroke mrs and age were identified as the strongest contributors to favourable and miserable outcome, and included in the simplified score. auc-roc was . ( ci% . - . ) and . ( ci% . - . ) for the prediction of favourable and miserable outcome respectively. r was . and . for the prediction of favourable (lack of fit p = . ) and miserable (lack of fit p = . ) outcome respectively. misclassification rate was % for favourable and % for miserable outcome with the simplified score. the simplified score had better discriminative power than ct-dragon for both outcomes (both p < . ). the ct-dragon score revealed acceptable discrimination in our cohort of both anterior and posterior circulation strokes, receiving a variety of treatment modalities. the simplified score had a better discrimination, while maintaining comparable and good specificity and misclassification rate for miserable outcome. the simplified score needs further validation in a prospective, multi-centre study. compliance with ethics regulations: yes. rationale: the gold report represents a major revision to gold strategy guidelines. it brings new recommendations regarding diagnosis, severity assessment, and both pharmacologic and non-pharmacologic treatment of copd. however, adherence to evidence-based therapeutic guidelines is often poor in low-income developing countries and represents a significant barrier to optimal management. the setting up of an lma-fastrach (desaturation). a case of glottic edema has been noted. discussion: this study shows a very high success rate with this technique ( . % in the first trial and . % in the second trial), in the context of a predictable difficult intubation. the video-airtraq allows a very good visualization of laryngeal structures, a shortening of the duration of intubation, and is rarely responsible for immediate or secondary complications. all the data in the literature go in the same direction. conclusion: at the end of this work, our perspectives are to update the difficult intubation procedure, integrating the video-airtraq into our algorithm, as well as into our difficult intubation trolley. to take into consideration the cost of this device to eventually generalize it to all our structures. compliance with ethics regulations: yes. ) and beds of continuous monitoring. the activity of the cp is organized in a medical visit in the morning and in conducting projects in the afternoon. the activity is presented using a -years balance sheet results: the activity of pharmaceutical interventions (pi) or answers to requests from teams is shown in table . the solicitations doubled the second year. the cp is involved in the conduct of internal or polar projects (set up of cooperative sedation, nutrition…), the good use of health products (relay iv/po, infusion, crushed tablets and compatibility with gastric probe, drug incompatibilities, proton pump inhibitors…), the efficiency of the drug circuit (link with the pharmacy, reflection on the improvement of the circuit, regular meetings with nurses), medico-economic analysis of health products spending and the formalization of actions by protocolisation. he is also very involved in clinical research: patient screening, clinical study setup: blipic study (beta-lactam's dosing in pneumonia in icu in patients treated by continuous renal replacement therapy; clinicaltrials nct ) or in candiarea project (invasive infections to candida and preemptive treatment guided by biomarkers; in progress). a satisfaction survey submitted at months to nurses ( answers/ ) or to doctors/ residents ( / ) reported cp competence in the accompaniment of teams (> %) [in medico-economical, contribution of knowledge, vigilance reflex…], relevance of information transmitted (> %) [administration of drugs, dosage adjustments, …] and his relationship adapted to the units (> %) [communication, availability] . the development of clinical pharmacy in icu involves mastery of the specificities of icu by the cp, requiring a learning period and relationships adapted to clinical situations and teams. many health products projects specific to critical care are coordinated by the cp and made possible by medical and paramedical involvement. the cp appears as a vector of good use both in medical (reasoned prescription) and paramedical (good practices) with increasing solicitation of teams since his arrival. this reception has been facilitated by an innovative approach of clinical pharmacy deployment in our icu on an impulse of the clinical pole compliance with ethics regulations: yes. predicting models such as the news has been developed in the emergency department, but it has only been fewly evaluated in the icu. heart rate variability (hrv) reflects the autonomic nervous system response in various pathological situations and may vary according to patients' physiological status. the rox index, which reflects the acute respiratory failure severity, seems to be a good predictor of high-flow nasal canula failure. the aim of this study was to evaluate the potential value of news, hrv and irox (inversed rox) as poor outcome predictors, using artificial intelligence and machine learning. a retrospective analysis of a prospective datawarehousing project (reastoc clinicaltrials identifier nct ) on icu patients who did not require invasive ventilation. physiological parameters were collected on admission, within a -h delay. news, hrv (in time, frequency, and non-linear domains), and irox were computed and integrated into the prediction model. analysis was performed using medcalc and matlab machine-learning work-package. results: one hundred and twelve patients were included. patients who died in the icu (n = ) had highest news as compared with icu survivors ( . [ . - . ] vs. . [ . - . ] respectively; p = . ). the irox was higher ( . [ . - . ] vs. . [ . - . ], p = . ) and most hrv parameters also depicted higher values for icu survivors. considering a composite icu prognostic outcome parameter (mortality and/or need for any form of respiratory assistance and/or an icu los > median los), there was also a difference for news, hrv and irox (p < . ). the best value to predict icu mortality for news was (auc = . , p = . ), irox > . (auc = . , p = . ) and hrv (shannon entropy) > . (auc = . , p = . ). the best model to predict the need fo respiratory assistance combines irox and hrv (sd /sd ; auc = . , p = . ). adding shannon entropy on this model predicts either the need for respiratory assistance and icu survival (respectively auc . , p = . and auc . , p = . ). in icu spontaneously breathing patients, news, irox and hrv are different in between survivors and patients who died. the best model to predict the need for respiratory assistance combines irox and hrv (sd /sd ). compliance with ethics regulations: yes. rationale: sepsis is known for its important mortality in critically ill patients. the last guidelines defined sepsis as life threatening organ dysfunction. it rejected the concept of systemic inflammatory response syndrome (sirs) associated to suspected or confirmed infection, and considered the concept of dysregulated response to infection. actual guidelines recommend the quick sequential organ failure assessment score (qsofa) to identify patients with sepsis especially when outside intensive care unit. thus, outcomes have mainly to judge the value of sirs in the sepsis- era. the purpose of our study was to compare whereas qsofa score or the sirs criterion are superior to predict in-hospital mortality, shock and mechanical ventilation use in sepsis. our study includes patients in whom the sepsis- definition is met. therefore, this inclusion was retrospectively performed throughout emergency department (ed) admission cases for clinically suspected infection. we collected patients admitted to ed for sepsis. mean age was years ± with bornes of and . men were % of the patients. death occurs in . % of patients, sepstic shock in % and the use of mechanical ventilation in . %. qsofa ≥ has a significant association with in-hospital mortality (p < . ) but not sirs ≥ ( . ). neither qsofa ≥ nor sirs ≥ has association with the use of mechanical ventilation (p = . vs. p = ). whereas, both have a significant association for prediction of septic shock. the absolute sensitivity and negative predictive value in our study can be explained by the small size of our sample. this needs confirmation with literature data about the fact that sirs criterion are superior in term of sensitivity and npv than qsofa to predict septic shock. despite the weak odds ratio (or) of sirs before that of qsofa and the poor specificity and positive predictive value (ppv), we can conclude that sirs according to its sensitivity and npv, seems to persist useful in the sepsis- era as a reliable prognostic tool in the ed. this may need more large studies for confirmation. conclusion: despite sirs has no significant association with mortality in sepsis, it has largely higher sensitivity and superior npv to predict septic shock than qsofa in ed. compliance with ethics regulations: yes. our study aimed to determine the predictive factors of mortality in our patients. retrospective study over years in the intensive care unit of the hospital august. all patients with septic shock were included. a p value < . was considered significant. results: patients were collected. the age ranged from to years old. the average duration of hospitalization in pre-intensive care was days. the reasons for admission: (febrile respiratory distress: % of cases, polytrauma: % and % for sepsis), the most frequent infections: pulmonary ( %) and blood ( %). % received prior antibiotic therapy and % were immunocompromised. the overall mortality was %. the analytical study of the data shows that the age, the length of stay before admission in intensive care and that in intensive care, fever, hypothermia, slimming, hypotension, collapse, failures (respiratory, hematological, renal, hepatic and neurological) and the use of catecholamines are correlated with mortality, whereas sex, chest pain, tachycardia or bradycardia and mottling are not predictive of mortality. conclusion: despite improved techniques for the diagnosis and treatment of patients with septic shock, mortality remains high, especially in the presence of certain risk factors, hence the value of prevention in immunocompromised patients and the reduction in their length of stay in a hospital setting. compliance with ethics regulations: yes. conclusion: p. mirabilis is among the leading bacteria responsible for nosocomial infections in icu. they are emerging highly drug resistant pathogens whose incidence is rapidly increasing in icu. so that, it early identification with in vitro testing is of paramount importance to the success of infectioncontrol efforts. compliance with ethics regulations: not applicable. rationale: influenza is a potential lethal disease causing dozens of thousands excess deaths per year both in europe and in the united states. besides hygiene procedures, vaccination is a cornerstone of influenza prevention and guidelines recommend for vaccination among health workers (hw), especially if they are in close contact with frail people. despite these recommendations, the vaccination coverage is low among health workers both in europe and in the us. the relevance of a mandatory vaccination for health workers is currently a hot topic but data are scarce regarding intensive care unit health workers' opinion. patients and methods: health workers from medical, surgical and polyvalent icus received a link to the electronic record of the survey. results: among the icus, icu health workers (hw) (medical: and paramedical: ) were questioned. three hundred and forty-one icu ( %) answered, ( %) medical health workers (mhw) and ( %) paramedical health workers (phw) (p < . ). among mhw / ( %) were vaccinated vs only / ( %) phw (p < . ). discrepancies exist between medical and paramedical icu health workers' opinions and beliefs about vaccination for influenza and its acceptance. medical health workers were more prone to consider influenza as a potentially lethal disease occurring not only among frail people but also in healthy people, to consider the vaccine efficient and safe. to agree with "vaccination for influenza is mostly related with gain for pharmaceutical industry" (or: [ . - ] ) and to disagree with "the risk of guillain-barré syndrome is higher after an episode of influenza than after vaccination for influenza" (or: . [ . - ] ) were independently associated to the disagreement with a mandatory vaccination for icu hw. conclusion: vaccination for influenza should be strongly recommended as a tool of individual protection for icu health workers as for general population. as confidence in vaccine efficacy and concerns about vaccine side-effects impact the vaccination rate, objective information should be provided to icu health workers about the efficacy and the side effects of vaccination for influenza. compliance with ethics regulations: yes. rationale: intra-abdominal infections are a major cause of morbidity and mortality. sfar recommendations on this topic were published in february . the purpose of this work was to evaluate whether our antibiotic therapy was adequate for these recommendations and whether they were adapted to our unit. the secondary objectives were to look for different risk factors for mortality, to evaluate the impact of inappropriate antibiotic therapy, to evaluate the relevance of carbapenem prescription. this is a single-center retrospective observational study of secondary peritonitis in the tourcoing intensive care unit. for each peritonitis, the epidemiological data and the co-morbidities of the patients were collected. bacteriology and anti-infectious therapies were described to determine the rates of adaptation of our antibiotic therapy and that recommended by sfar. the adequacy of our treatments to the recommendations was also quantifiable. the description of the stay, the occurrence of a death was specified. results: peritonitis were included. the rate of adaptation of the sfar antibiotic therapy was %. the rate of adaptation of our antibiotic therapy was % and its adequacy rate of %. the main differences in prescriptions concerned over-prescription of antifungals, molecule against gram positive bacillus and a sub-prescription of aminoglycosides and beta-lactams, in particular carbapenems. the different mortality risk factors found were sofa score > (or . % ci . - . ), the charlson score > (or . % ci . - . ), the hollow organ perforation (or . % ci . - . ). a comparison of the appropriate or not antibiotic groups did not reveal a significant difference in mortality, number of surgical revision and length of stay. in % of nosocomial peritonitis, antibiotic therapy with carbapenem was recommended. after recovery of microbiological data, it was only necessary for . % of cases. conclusion: our work showed a low rate of compliance with sfar recommendations. these recommendations are applicable to our service by providing a particular reflection for fungal infections. our study does not show a correlation between mortality and inadequate antibiotic therapy, surgery remaining the major treatment. compliance with ethics regulations:yes. rationale: acinetobacter baumannii is a gram-negative opportunistic bacteria that has gained several drug resistance mechanisms over the last decades. analysis of a. baumanii's resistance profile helps to establish a prompt control and a prevention program. the aim of this study was to evaluate the epidemiology and antimicrobial resistance of a. baumannii isolates in a trauma and burn center in tunisia. patients and methods: retrospectively, we studied all strains of acinetobacter baumannii isolated over a -year period (from january to december ). conventional methods were used for identification. antimicrobial susceptibility testing was performed with the disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. data were analyzed using the sir-system. minimum inhibitory concentration (mic) of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may . results: during the study period, non-repetitive strains of acinetobacter baumannii were isolated representing . % of all isolates, % of gram-negative bacilli (gnb) and . % of non-fermenting gnb. in our center, infections due to a. baumannii were endemic with epidemic peaks. a. baumannii was mainly isolated from burn intensive care unit ( %) and anesthesiology department ( . %). the most frequent sites of isolation were blood cultures ( . %), catheters ( %), respiratory specimens ( . %) and skin samples ( % sampling duration is also reduced, improving workflow. evaluators consider that bronchosampler rationalizes the cumbersome sampling process and that the closed system design reduces the risk of losing sample or sample contamination. the set-up, the suction capacity, the sampling quality and quantity have all been evaluated better or far better than that usually observed with usual sampling techniques and devices. finally, ( %) of users prefer bronchosampler to commonly used method. conclusion: this satisfaction survey shows that with its simple but revolutionary design, bronchosampler brings a real effective benefit in sampling procedure enabling the clinician to perform it alone, and ( %) of the survey evaluators consider that bronchosampler should replace their current practice. compliance with ethics regulations: yes. rationale: the possibility of having a sensitive, specific and prognostic biological marker for bacterial infections is a considerable challenge. a step was taken with the discovery of pracalcitonin. patients and methods: this is a prospective observational cohort study of patients in the medical resuscitation department of the university hospital of casablanca during the -month period, including patients in whom the pct was dosed. the data collected allowed us to form two groups according to the pct value: pct+ group with pct > ng/ml and pct− group with pct < ng/ml. the statistical analysis of these different data was carried out using epi info software version . . . results: % of our patients had a bacterial infection and % did not have one. we also distinguished community infections ( % of i+ patients) and nosocomial infections ( % of i+ patients). we found that the highest rates of pct were in nosocomial infections and the lowest pct rates were found in community-acquired infections. then, in each type of organ involvement we tried to vary the pct thresholds to . - and ng/ml in order to find the best threshold for which pct allowed to diagnose bacterial infection, justifying our choice of departure. we concluded that the best pct cut-off value in general was ng/ml, because it gave us the best sensitivity/specificity ratio ( % and % respectively) with a positive predictive value of % and a negative predictive value of %. the link between pct and bacterial infection was moderate (yule q-factor at . ). by analyzing the different therapeutic aspects, we showed that % of our patients had been treated with atb before the pct assay and that the broadest spectrum antibiotics available to our service were used in patients with pct levels the highest. finally, concerning the evolution, the higher the rate of pct, the higher the death rate, especially since % of patients with pct > ng/ml died. conclusion: procalcitonin is considered to be one of the best markers of systemic bacterial infection. indeed, its elevation is earlier than that of crp and its specificity is better compared to il- and il- . the rate of procalcitonin remains low in the presence of viral infection. procalcitonin is also a prognostic marker, its elevation is correlated with the severity of the infection, and its decrease is a good indicator of the effectiveness of antibiotic therapy. compliance with ethics regulations: not applicable. rationale: due to induction immunosuppression infection is the most common cause of mortality within the first year after lung transplantation (ltx). the management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. we sent by email a survey to ltx centers around the world dealing with daily clinical vignettes concerning perioperative antibiotic therapy. we considered perioperative period as the period of the transplant surgery (per operative) and the postsurgery time before any infection occurrence (postoperative). after general questions on local practices, we asked each center for colonization definition and their diagnostic methods for microbial screening in recipients and donors. the clinical cases were related to specific issues concerning the management of antibiotic therapy in different clinical situations, including no prior colonization, prior colonization with sensitive or multi-drug resistant (mdr) microorganisms including prior colonization with mdr bacteria not sensitive to beta-lactams. the invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center between june and september . we received a total of responses from countries, mostly from western europe (n = ) and the usa (n = ), (fig. ) . systematic screening for bronchial colonization before ltx was mostly performed with sputum samples ( %), regardless of the underlying lung disease. definition of colonization was very heterogeneous and the delay between the last bacterial isolation in pre-transplant and the ltx to consider if the therapy should target these bacteria varied between week and more than year. in recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin/tazobactam, cefepime, ceftazidime, carbapenems) were reported in % of the centers, and antibiotics with activity against methicillin-resistant staphylococcus aureus (mainly vancomycin) were reported in % of the centers. for these recipients, the duration of antibiotics reported was days ( %) or less ( %) or stopped when cultures of donor and recipients were reported negatives ( %). in recipients with pre-transplant colonization, antibiotics were adapted to the susceptibility of the most resistant strain isolated in pre-transplant samples and given for at least days ( %). conclusion: practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. the antibiotic duration reported was longer for colonized recipients. compliance with ethics regulations: not applicable. the vancomycin was therefore considered as justified or not and appropriate or not. occurrence of nephrotoxicity and supratherapeutic exposure in this study group was compared to critically ill children control group. results: thirty one children receiving vancomycin lines of treatment whose ( %) observed a risk of acute kidney injury (aki) (n = ) and an aki (n = ) during the vancomycin treatment period were included. there was a trend to inversed relationship between plasmatic concentrations of vancomycin and estimated creatinine clearance (r = . ). seven patients observed a nephrotoxicity related to vancomycin, they had a higher plasmatic concentration of vancomycin (p = . ). seven patients ( %) had a supratherapeutic exposure to vancomycin. nephrotoxicity and supratherapeutic exposure were higher in children with or combined liver-kidney transplantation than in comparative critically ill children group. we found blood stream infection due to the central catheter and blood stream infections probably due to the central catheter. one hundred thirtyfive bacteria were identified of which ( %) were staphylococcus coagulase negative. nineteen ( %) lines of vancomycin were appropriate and ( %) were justified. conclusion: vancomycin could have been avoided in one third of children with liver or combined liver-kidney transplantation during the early phase of postoperative stage. vancomycin is associated with a risk of both nephrotoxicity and supratherapeuric exposure. vancomycin should be used with caution, appropriate indications and dosing in this vulnerable population. compliance with ethics regulations: yes. rationale: early bacterial infection is a major and severe complication occurring within the first month after pediatric liver transplantation (lt). the rise of antimicrobial resistance, especially extended-spectrum beta lactamase producing enterobacteriaceae (esbl-pe), is henceforth a concern for these patients. this study aimed to assess the epidemiology of early bacterial infections, including those caused by multidrugresistant (mdr) pathogens, and to identify the risk factors for infection. rationale: the number of cancer patients admitted to emergencies is clearly increasing and digestive oncology is the leading cause of consultation. the aim of this work is to identify the epidemiological factors, the therapeutic modalities as well as the predictive factors of mortality and to compare them with the data of the literature. patients and methods: patients admitted to visceral emergencies for an urgent syndrome revealing or complicating a primary or secondary digestive cancer, and who required immediatemedical and/or surgical intervention and who had stayed at the surgical resuscitation level in our hospital center for a duration of years. several data were entered on excel and analyzed using the spss version software.-epidemiological, concerning age and sex; -clinics including risk factors, history, general condition of the patient and clinical examination data; -para-clinical, interesting biological assessments, and morphological examinations-medical and surgical therapeutics; -postoperative follow-up-treatment results. the three most frequent sites were rated in order of increasing frequency: colo-rectum ( %), pancreas ( %), and stomach ( %). the age group most found was age over years with % of cases, % of patients had under years. this series includes men and women with a sex ratio of , . the installation method was mostly gradual with % of cases. our patients have consulted for urgent clinical presentations mainly occlusive syndrome noted in % of patients. abdominal ct was the first examination performed, followed by abdominal ultrasonography in % and %, respectively. the therapeutic management was medico-surgical. the surgery done in % of patients, % for palliative indication: % were operated for an ostomy discharge, % for a digestive bypass, % for a palliative resection and % for a stoma feeding. postoperative outcomes were % morbidity and % mortality. the main cause of death was septic shock in % of cases, thanks to multivariate statistical analysis three factors were deduced significantly related to mortality: the asa score: p = . ; or = . ; ic: [ . ; . icu and hospital mortality rates were % (n = ) and . % (n = ), respectively. ten patients were alive months after with a median rankin score at [ - ]. more than half of the patients without stupor had a favorable neurological outcome (fig. ) . in univariate analysis, mechanical ventilation and stupor were correlated with mortality, whereas dic and apl were not. by multivariate analysis stupor was the only factor significantly associated with a higher mortality (hr: . [ . - . ] ). conclusion: intracranial hemorrhage is associated with a high mortality rate in al patients, stupor at the onset of intracranial bleeding being independently associated with poor outcome. up to one third of patients will nevertheless survive and experience a favorable neurological outcome. compliance with ethics regulations: yes. neurological outcome assessing by modified rankin scale according to stupor or coma at intracranial hemorrhage diagnosis (blank reflect missing data) rationale: sinusoidal obstruction syndrome (sos, previously known as veno-occlusive disease) is a complication of high dose chemotherapy, frequently occurring during bone marrow transplantation (bmt). severe sos is associated with a high mortality rate, related to multi-organ failure (mof). defibrotide being the only available option for prevention and treatment. prognosis of patients with sos requiring intensive care unit (icu) admission remains unknown. the primary objective was to assess the outcome of these patients. secondary objective was to assess risk factors associated with hospital mortality. patients and methods: retrospective study conducted between january and july in french icus. critically ill adult patients with sos (according to ebmt classification) who received defibrotide were included. results are reported as median [iqr] or number (%). adjusted analysis was performed using cox model. results: seventy-one patients were included with a median age of years . underlying hematologic diseases were acute myeloid leukemia ( %), lymphoma ( %),myelodysplasia/myeloproliferative neoplasm ( %) or acute lymphoid leukemia ( %). sos occurred during myeloablative allogeneic bmt ( %), reduced conditioning allogeneic bmt ( %), autologous bmt ( %) or chemotherapy ( %, including gemtuzumab ozogamycin in patients). median sofa score at icu admission was ]. ebmt prognostic score was often "very severe" ( %). main reasons for icu admission were respiratory failure (n = ), acute renal injury (n = ), shock (n = ), liver failure (n = ), coma (n = ) and monitoring (n = ). median bilirubin level at icu admission was µmol/l [iqr - ] and platelets count g/l . mechanical ventilation (mv), vasopressors, and renal replacement therapy (rrt) were required in % (n = ), % (n = ) and % (n = ) of patients, respectively. sixteen patients receiving defibrotide experienced bleeding events. icu and hospital mortality rates were % and % respectively, mainly related to organ dysfunction. in univariate analysis, delayed defibrotide initiation, bilirubin level, organ supports, sofa, and ebmt scores were associated with hospital mortality. cox model identified older age (hr . , % ci . - . ), mv (hr . , % ci . - . ), rrt (hr . , % ci . - . ), as associated with mortality. prophylactic defibrotide was correlated with a better outcome (hr . , % ci . - . ). similar results were observed after adjustment for center effect. conclusion: when organ support is required, icu management is associated with high mortality. organ support (namely rrt and mv) and older age were associated with poor outcome. prophylactic defibrotide was associated with survival either due to selection process or to efficacy in this setting. additional studies are needed to confirm these results. compliance with ethics regulations: yes. rationale: prognosis of critically ill immunocompromised patients (ciip) has improved over time. neutropenia is common and is found in one third of these patients. prognostic impact of neutropenia remains controversial and little data focus on ciip admitted in a context of acute respiratory failure (arf). primary objective was to assess prognostic impact of neutropenia on outcome of these patients. secondary objective was to assess etiology of arf according to neutropenia. patients and methods: retrospective analysis of prospective multicenter multinational dataset. adults immunocompromized patients with arf were included. adjusted analyses included ( ) a hierarchical model with center as random effect; ( ) propensity score (ps) matched cohort; and ( ) adjusted analysis in the matched cohort. results: overall, patients were included in this study. median age was [iqr - ] and patients ( . %) were of female gender. median sofa score was [ ] [ ] [ ] [ ] [ ] [ ] [ ] and ps was [ ] [ ] [ ] [ ] . main immune defect were hematological malignancy in patients ( %), solid tumor in ( %), systemic disease in ( . %), and other immunosuppressive drugs in ( %). neutropenia at admission was observed in patients ( %). initial oxygenation strategy was oxygen in patients ( %), high flow nasal oxygen in ( %), non-invasive ventilation in ( %) and invasive mechanical ventilation in ( %). before adjustment, hospital mortality was significantly higher in neutropenic patients ( % vs. % in non-neutropenic patients; p = . ). after adjustment for confounder in a mixed model, neutropenia was no longer associated with outcome (or . , % ci . - . ). after ps matching, neutropenic and non-neutropenic patients were compared. hospital mortality was similar in both groups ( % vs. % respectively; p = . ). after adjustment for variables associated with mortality, neutropenia was not associated with hospital mortality (or . , % ci . - . ). arf etiologies were distributed similarly in both neutropenic and non-neutropenic patients (fig. ) , main etiologies being bacterial pneumonia ( % vs. %), invasive fungal infection ( % vs. %), pneumocystis jiroveci pneumonia ( % vs. . %), and undetermined etiology ( % vs. %) (p = . ). conclusion: neutropenia at icu admission is not associated with hospital mortality in this cohort of ciip admitted for arf. surprisingly, arf etiology did not differ despite the multiplicity of observed immune defects. compliance with ethics regulations: yes. rationale: hepatic dysfunction (hd) is commonly observed in patients with hematologic malignancies and associated with an increased mortality in allogeneic hematopoietic stem cell transplantation patients. we aimed to assess incidence, risk factors and prognostic impact of hd in a large multicenter cohort study of critically ill patients with hematologic malignancies. patients and methods: this research was a post hoc analysis of a franco-belgian multicenter prospective study assessing the prognosis of patients with hematologic malignancies admitted to intensive care unit (icu) between january and may . hd was defined as serum total bilirubin ≥ µmol/l at icu admission. for patients with hd, a review of medical hospital records was performed by an expert panel to assess management of hd by attending physicians. results: among the patients with hematologic malignancies admitted to icu, were included in the study, mainly patients with non-hodgkin lymphoma ( . %) or acute myeloid leukemia ( . %). hd at icu admission occurred in patients ( . %). factors independently associated with hd were the use of cyclosporine (or = . , % ci . - . , p < . ) and antimicrobial treatment (or = . , % ci . - . , p = . ) before icu admission, abdominal symptoms at icu admission (or = . , % ci . - . , p < . ), ascites (or = . , % ci . - . , p = . ), hepatic charlson comorbidity (or = . , % ci . - . , p = . ), increased creatinine at icu admission (or = . , % ci - . , p = . ), neutropenia (or = . , % ci . - . , p = . ) and myeloma (or = . , % ci . - . , p = . ). hospital mortality was . % and . % in patients with hd and patients with no hd respectively (p < . ). hd appeared as an independent factor of hospital mortality after adjustment with other organ failure (oradj = . , % ci . - . , p = . ). factors independently associated with hospital mortality among patients with hd at icu admission are reported in table . etiologic diagnoses for hd by physicians were undetermined for patients ( . %) including ( . %) for whom the existence of hd has not even been mentioned in the medical record. investigations were performed in % and only % of patients received a specific treatment for hd. conclusion: hd at icu admission is common, underestimated, poorly investigated, and impairs outcome in critically ill patients with hematologic malignancies. hd should be considered and managed as other organ dysfunctions. it raises the importance of an early severity assessment of hd and a development of diagnosis strategies to get therapeutic options, in close collaboration between hematologists and intensivists. compliance with ethics regulations: yes. rationale: acute respiratory failure (arf) is the main cause for admission to the icu for patients with hematological malignancies (hm). viral pneumonia is poorly described in this population. respiratory viruses pcr is a rapid and sensitive diagnostic tool. thoracic ct allows to guide the diagnosis but is also poorly described. the primary objective was to describe ct features suggesting viral pathogenicity. secondaryobjectives were to assess risk factors associated with the use of invasive mechanical ventilation (imv) and icu mortality. rationale: high-dose methotrexate (hd-mtx) is commonly used in the treatment of solid tumours and hematological malignancies. severe toxicities are frequent, leading to organ dysfunction, multiple organ failure and death. outcome of these patients when critical illness occurs is poorly studied. this study aims to describe mtx-induced toxicities and to assess outcome in critically ill patients. in this retrospective study conducted in the icu of one university hospital between january and december , all the patients who were given hd-mtx (single dose greater than mg/m ) in the icu were included. results are presented as median [interquartile range] and number (percent). results: patients ( men and women) aged years [ - ], were included. b-cell lymphoma had been diagnosed in patients (burkitt, n = ; diffuse large b cell lymphoma with cns (central nervous system) involvement, n = ; primary cns lymphoma, n = ) and t-cell lymphoma in two patients. patients were mainly admitted for coma (n = ; %) or acute kidney injury (n = ; %). mtx was administered at a median dose of . g [ - ] . fourteen patients had concomitant medication interacting with mtx. median mtx clearance was days [ ] [ ] . frequent mtx-related complication were mucositis (n = , %), diarrhea (n = , %) or hepatic failure (n = , %). during icu stay, patients experienced acute kidney injury (kdigo stage . [ ] [ ] ). two patients received carboxypeptidase and three underwent dialysis. overall, patients ( %) required mechanical ventilation, ( %) vasopressors. hospital mortality was % (n = ). cox model identified mtx concentration h after administration higher than . µmol/l as associated with hospital mortality (hr . , % ci . - . ) (fig. ) . conclusion: to our knowledge this is the first study assessing characteristics and outcome of critically ill patients receiving hd-mtx. mtx concentration at h was associated with hospital mortality. despite underlying malignancy, icu support of these patients was associated with a meaningful survival. compliance with ethics regulations: yes. rationale: high-dose methotrexate ( g/m ; hdmtx) is the cornerstone of chemotherapy in acute lymphoblastic leukemia (all) and several high-grade non-hodgkin lymphoma (hnhl). despite standardized prevention, acute kidney injury (aki) and other life-threatening complications still occur. given the cost of glucarpidase, an enzyme that metabolizes mtx in few minutes, and the complexity of hematological patients admitted to the icu, a better comprehensive view of the factors that predict hdmtx toxicity, as well as the role of glucarpidase as rescue therapy in patients with organ failure, is mandatory. patients and methods: retrospective monocenter study including all the adult patients referred for all or hnhl in a french university hospital, and who received hdmtx. aki was defined according to the kdigo classification. univariate analysis (fischer exact or mann-withney tests) followed by multivariate analysis (stepwise logistic regression) were used to identify before hdmtx the clinical and biological predictive factors of aki. outcomes following glucarpidase were also addressed. results: from dec- to sept- , patients received hdmtx (median dose g/m ; all n = , hnhl n = ), totalizing hdmtx pulses. sixty-nine patients ( . %) developed aki after a median time of days (stage n = , stage n = , stage n = including one requiring dialysis in the first week). by multivariate analysis, only age, body mass index and a diagnosis of all were significantly and independently associated with the risk to develop aki. mtx exposure (maximal serum concentration at h - ) was also associated with aki (auc . , p < . ). glucarpidase was used in patients ( %) that differed by a higher age and bmi, and a lower basal egfr. glucarpidase was followed by a rapid renal improvement but serum creatinine did not return to baseline ( vs. micromol/l). thirty patients with aki or delayed mtx elimination did not receive glucarpidase but none required renal replacement therapy and egfr was only slightly but not significantly reduced at the end of follow-up. extra-renal adverse-events (rbc and platelets transfusions, neutropenia, hepatitis, severe diarrhea, mucitis) were more frequent in patients that developed aki. eighteen patients were admitted to the icu, including and that required mechanical ventilation or vasopressor drugs, respectively. conclusion: few actionable factors predict the development of aki after hdmtx, suggesting additional genetic factors. aki was reversed by glucarpidase but progression toward ckd was the rule. further studies will have to identify patients that will actually beneficiate from glucarpidase. compliance with ethics regulations: yes. khaoula ben ismail, sana khedher, ameni khaled, nassereddine foudhaili, mohamed salem usi digestif-service de gastroenterologie-eps charles nicolles.tunis-tunisie., tunisia, tunisia correspondence: khaoula ben ismail (khaoula @hotmail.fr) ann. intensive care , (suppl ):p- rationale: infection is common and accounts for major morbidity and mortality in cirrhosis. patients with cirrhosis are immunocompromised and have increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. we aimed to evaluate the impact of infection on hepatic encephalopathy. patients and methods: this is a prospective study, conducted over a period of years from january to december . consecutive patients with approved decompensated cirrhosis admitted to our department are included. all clinical and biological data were collected from the medical records. univariate and multivariate analysis were used to identify the impact of infection on hepatic encephalopathy. results: a total of patients diagnosed with decompensated cirrhosis were enrolled in this study. mean of age was years ( - ). sex ratio was . . hcv ( %) was the main etiology of cirrhosis. the reasons of hospitalization were: oedema with ascitic syndrome ( % of cases), digestive bleeding ( % of cases), fever ( % of cases), and encephalopathy ( % of cases). patients with infection seemed to have a high incidence of hepatic encephalopathy with % versus % when the patients are none infections. the results also showed that in those with hepatic encephalopathy, an effective antibiotic treatment accelerates significantly wakefulness under h with a rate of % vs. % (p < . ) . in addition, the infection does not influence mortality or length of stay compared to other complications such as digestive bleeding. conclusion: we found that infection caused more episodic hepatic encephalopathy than other complication and an effective antibiotherapy accelerate wakefulness. compliance with ethics regulations: yes. rationale: hepatic encephalopathy (he) is a common cause of hospitalization in patients with cirrhosis. pharmacologic treatment for acute (overt) he has remained the same for decades. to compare polyethylene glycol electrolyte solution (peg) and lactulose treatments in patients with cirrhosis admitted to the hospital for he. we hypothesized that rapid catharsis of the gut using peg may resolve he more effectively than lactulose. patients and methods: this is a prospective study, conducted over a period of years. from janury to december , we have been interested in cirrhotic patients with hepatic encephalopathy. all clinical and biological data were collected from the medical records. univariate and multivariate analysis were used to identify the difference beteween peg and lactulose in the treatement of hepatic encephalopathy. results: a total of patients diagnosed with decompation of cirrhosis were enrolled in this study. mean of age was years ( - ). sex ratio was . . hcv ( %) was the main etiology of cirrhosis. the hospitalization reasons were: edematous-ascitic syndrome in %, gastro-intestinal bleeding %, fever in %, and encephalopathy was present in % of cases. a total of patients were randomized to each treatment arm. baseline clinical features at admission were similar in the groups. twelve of patients in the standard therapy arm ( %) had an improvement of or more in hesa score, thus meeting the primary outcome measure, compared with of evaluated patients receiving peg ( %) (p < . ). the mean ± sd hesa score at h for patients receiving standard therapy changed from . ± . to . ± . compared with a change from . ± . to . ± . for the peg-treated groups (p = . ). the median time for he resolution was days for standard therapy and day for peg (p = . ). adverse events were uncommon, and none wasdefinitely study related. conclusion: we found that peg led to more rapid he resolution than standard therapy, suggesting that peg may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute he. compliance with ethics regulations: yes. acute pancreatitis and pregnancy janati adnane, lina berrada obstetric intensive care unit, casablanca, morocco correspondence: janati adnane (adnanejanati@gmail.com) ann. intensive care , (suppl ):p- rationale: the association of acute pancreatitis and pregnancy is rare but not negligible, it often cause a diagnostic problem given the gravidal context that can lead to serious repercussions. the objective of our study is to assess the particularities in the diagnosis, management and prognosis of acute pancreatitis during pregnancy patients and methods: this is a retrospective study about cases of acute pancreatitis occurred during pregnancy over a -year period ( - ) at the obstetric intensive care unit of the meriem maternity hospital in the chu ibn rochd casablanca. a retrospective analysis of the medical files of these patients was carried out, considering epidemiological and etiological criteria, the treatments administered and maternal/fetal fate. we found cases during this period, with an incidence of / . the average age of onset was years, % of cases occurred in the rd trimester. epigastric pain and vomiting were the common symptomatology. ultrasound showed biliary lithiasis in % of cases with increased pancreas size in % of cases. maternal mortality was zero. uncomplicated benign forms are the most common ( %). severe hypokalemia was found in % of patients. neonatal morbidity was marked by six premature deliveries. among them, a newborn died at day- of life discussion: the association of acute pancreatitis and pregnancy is rare, more frequent during the rd trimester, it mainly affects the young woman. lithiasic biliary pathology remains by far the most frequent etiology. the diagnosis is clinical most often represented by epigastralgia with vomiting and biological via lipasemia and amylasemia dosage. uncomplicated benign forms are the most common. hydroelectrolytic disorders are often found. abdominal ultrasound allows the etiological diagnosis. the treatment is above all symptomatic whose objective is the digestive rest, the correction of the hydroelectrolyte disorders but first of all relieve the pain. conclusion: acute pancreatitis is a rare event in pregnant women, but can have a maternal and fetal prognosis. it must be systematically evoked in front of the acute abdominal pains of the pregnant woman because the confirmation of the diagnosis is easy and the maternal results depend mainly on therapeutic management. prematurity remains the predominant factor in neonatal morbidity. compliance with ethics regulations: not applicable. rationale: aclf is a clinical concept defined in patients with chronic liver disease who presented organ failure(s) secondary to an acute decompensated event. liver transplantation in this indication showed good results in selected patients. the aim of this prospective study was to evaluate the outcome and the factors associated with a favorable selection to liver transplantation in this population. patients and methods: all consecutive patients admitted to the icu with cirrhosis and aclf, were recruited. patient with age < years or with fulminant hepatitis were excluded. results: between july and february , cirrhotic patients were admitted to icu. mean age was . ± . years ( . % male). cirrhosis was due to alcohol in . % of the patients. aclf grading at admission was: . % aclf (n = ), . % aclf (n = ), . % aclf (n = ), and . % aclf (n = ). of the patients, . % (n = ) were considered to be eligible for a transplant project and were assessed for liver transplantation. the main reasons were alcohol abuse ( . %, n = ), death within days after admission ( . %, n = ) and rapid improvement of the liver disease. of the eligible patients, % were transplanted with a mean time between admission to icu and liver transplantation of . ± . days. twelve patients died on the waiting list ( % of the listed patients), mainly of septic shock. among those who were assessed for liver transplantation but not listed (n = ), . % died before the listing (n = ) and . % were not listed because of severe comorbidities (n = ). the global mortality rate was . % (n = ). the and days rate mortality were respectively . % and . %. the overall -month patient survival was respectively % and % in the transplant and non-transplant group (p < . ) for the entire cohort. among eligible patients, factors associated with the absence of liver transplantation, in the multivariate analyses, were mechanical ventilation (hr . , % ci rationale: body composition is known to be a prognostic factor in cirrhotic patients. however, the link between this and the prognosis of patients in intensive care unit (icu) is unknown. the computed tomography offer accurate estimations of muscle mass by analysing a cross-section usually going through the third lumbar vertebrae. this retrospective study aimed to assess the feasibility of body composition (bc) analysis in cirrhotic patients with septic shock, using computed tomography (ct) and evaluate the impact of bc (muscle mass, subcutaneous and visceral fat) on outcome. patients and methods: this retrospective study included cirrhotic patients with septic shock hospitalized in icu who underwent an abdomino pelvic ct scan within h of admission. we collected the surface areas of muscle mass and adipose tissue on the ct scans. we compared bc data with mortality and with the number of organ failures. the average age was years . the average child and meld scores were respectively . [ - ] and . . the prevalence of sarcopenia was %. it was not associated with a higher mortality rate at day (p = . ) or with a higher number of organ failures at day (p = . ). we observed a higher subcutaneous adiposity index in patients who died at day (p = . ) and in patients with renal insufficiency at admission (p = . ). there was a trend (p = . ) towards more visceral fat in patients who died in icu. the assessment by ct of body composition reveal evaluation of bc using ct is feasible and reproducible and may constitute a promising tool to evaluate in cirrhosis critically ill patients. visceral fat mass seems associated with poor outcome in cirrhotic patients with septic shock compliance with ethics regulations: yes. rachid jabi, mohammed bouziane chu mohammed vi, oujda, morocco correspondence: rachid jabi (jabirachid@gmail.com) ann. intensive care , (suppl ):p- rationale: the infection of the necrosis constitutes a pejorative element in the management of the necrotico-haemorrhagic pancreatitis, in the absence of the drainage the mortality approaches %. the morbidity and mortality of surgery can be avoided with minimally invasive treatments. purpose: to compare the morbidity and mortality of the two groups of post-ercp pancreatitis and the other etiologies. patients and methods: a retrospective study over years between and and a comparison between pancreatitis secondary to post-ercp and other etiologies of pancreatitis. a p value of . is considered significant. the surgical treatment used in cases of superinfection post ercp against seven cases of other etiologies of pancreatitis. high mortality in post-ercp pancreatic arm % vs. % (p = . ). high morbidity in the operated group % vs. % (p = . ) represented mainly digestive haemorrhages. duration of stay was significantly longer in the operated group vs. days (p = . ). thrombocytopenia and beta-lactamase-producing enterobacteria have further complicated management in the post-ercp infected pancreatitis arm. the antibiotic resistance of infected pancreatitis in post-ercp patients is . % for ciprofloxacin, . % for imipenem and % for amikacin. conclusion: pancreatitis the most common adverse effect of ercp with significant morbidity and mortality. the collaboration between the intensive care unit gastroenterologist and the surgeon improves management since the risk factors are mainly related to the patient and can not be modified. compliance with ethics regulations: yes. gautier nitel, aghiles hamroun, anne bignon, gilles lebuffe chru lille, lille, france correspondence: gautier nitel (gautier.nitel@gmail.com) ann. intensive care , (suppl ):p- rationale: liver transplantation (lt) has been recently experiencing an expansion of its indications, allowing patients with potentially more co-morbidities to access to transplantation. in our era of graft shortage, we should focus on the identification of the best lt candidates. the aim of our work is to study the determinants of early morbidity and mortality after lt from three angles: occurrence of a major cardiovascular event (mace) or acute renal failure (kdigo stage - aki) in the first days postoperative, and death in the year following lt. retrospective study investigating the occurrence of mace or aki (kdigo - ) within days post-operative and mortality at year after lt, including patients who received a first lt between january and december in our center. analysis of risk factors by a multivariate step-by-step analysis. statistical significance for p < . . data presented in odds ratio (or) rationale: infectious complications are frequently reported in critically ill patients supported by veno-arterial extracorporeal membrane oxygenation (va-ecmo) for refractory cardiogenic shock, but their diagnosis is challenging. no study has specifically studied bloodstream infection (bsi) in this population and some recommendations suggest performing systematic blood culture (bc). in our unit, systematic bc are daily sampled. we investigated the interest of systematic bc to detect bsi under va-ecmo. patients and methods: in a retrospective analysis ( - ), and after exclusion of patients dying within h, all adult patients from cardio-vascular intensive care unit supported by va-ecmo were included. systematic daily and "on demand" bc (at the physician's discretion) performed from va-ecmo implantation to days after withdrawal were analyzed. bsi was defined as at least one bc positive to a pathogen (except for contaminants bsi which required at least two positive bc with the same bacteria in h). multivariable logistic regression was performed to identify risk factors for positivity of systematic bc. rationale: fungal infections are constantly increasing in hospitals. indeed, the increase in these infections and especially candida yeast infections is almost parallel to the increase in the widespread use of a wide range of implanted medical devices such as catheters. for this reason, we have been investigating, isolating and identifying candida yeast colonizing vascular catheters and studying the epidemiological and clinical characteristics of patients with colonized catheters. patients and methods: it is a prospective, transversal study conducted at the intensive care and neurosurgery services of the sétif university hospital, evaluating the fungal colonization of vascular catheters. these are collected from hospitalized patients for a period of months. a culture of the distal end of the catheter is performed directly after its ablation. the results obtained showed that among the samples taken, six are colonized by the yeasts, the incidence is %. six yeast of candida spp were isolated, % of them were candida albicans species, . % candida parapsilosis and . % were candida glabrata. conclusion: it appears that colonization of catheters occurs most frequently in patients with the following characteristics: extreme ages of life, male sex, antibiotic therapy and length of hospitalization or prolonged catheterization. compliance with ethics regulations: yes. rationale: the threat of emergent extensively drug-resistant bacteria (exdr) dissemination worldwide is real. it has become a global public health issue. in fact, glycopeptides-resistant enterococcus faecium (gre) and carbapenemase-producing enterobacteriaceae (cpe) are the lead microorganisms in the high resistant bacteria category. the aim of our study was to characterize the molecular mechanisms and to determinate the antimicrobial susceptibility profiles of gre and cpe isolated from burn patients. patients and methods: prospectively, we studied all cpe and gre strains isolated from burn patients between january and december . all isolated microorganisms were identified on the basis of conventional microbiological techniques. antibiotic susceptibility testing was carried out by the agar disc diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. molecular characterization was performed by multiplex real-time pcr (cepheid, genexpert ® ) allowing detection of the most prevalent carbapenemase encoding genes (blavim, blandm, blaimp, (blaoxa- and blakpc) as well as the genes vana and vanb of gre. results: during the study period, exdr were isolated from burn patients. the most frequent sites of isolation were blood cultures ( %) and skin samples ( . %). cpe represented . % of isolated exdr ( strains). among them, the most frequently identified species was klebsiella pneumoniae ( . %) followed by enterobacter cloacae ( %). twenty-four cpe ( . %) expressed the blandm gene. the blaoxa- gene was found in strains ( . %) and ten strains ( . %) carried both genes. of the cpe, . % revealed ertapenem mic > mg/l whereas most strains were susceptible to imipinem and meropenem with . % and . % of susceptibility, respectively. the antibiotics showing the highest resistance rates were cefotaxime ( . %), piperacillin-tazobactam ( . %), ciprofloxacin ( . %) and amikacin ( . %). the most active agents were colistin and fosfomycin with . % of resistance for each. seven strains of gre were isolated ( . % of exdr). all of them expressed the vana gene, with vancomycin mic > mg/l. however, teicoplanin mics ranged from to mg/l. all gre strains were beta-lactam resistant and highly resistant to aminosides. linezolid and tigecycline were the only active antibiotics. the dissemination of these extensively drug-resistant bacteria must be contained by implementation of strict isolation methods and better hygienic procedures in order to limit their economical and health consequences. compliance with ethics regulations: yes. rationale: stenotrophomonas maltophilia has emerged as an important pathogen that induces nosocomial infections. it is a non-fermentative, gram-negative bacillus that causes severe infectious diseases, particularly bacteremia in the hospital setting. morbidity and mortality due to stenotrophomonas maltophilia seems to be high, particularly in critically ill patient. the aim of this study was to describe the clinical features, management and outcome of patients with stenotrophomonas maltophilia infections. patients and methods: this was a retrospective analysis of prospectively collected data of patients hospitalized in intensive care unit (icu) between january and december . collected data were: age, gender, comorbidities, severity scores on admission, prior infections, use of antibiotics, use of invasive devices (urinary tract catheter, or mechanical ventilation), microbiological data, and antimicrobial therapy and outcome. results: during the study period, patients with stenotrophomonas maltophilia infection were included, with a mean age of ± years. the simplified acute physiology score ii and acute physiology and chronic health evaluation ii on admission were respectively ± and ± . bacteremia caused by stenotrophomonas maltophilia was observed in patients ( %) and ventilator acquired pneumonia in two patients ( %). twenty four episodes were classified as primary bacteraemia and only one as secondary bacteraemia due to urinary infection. four patients ( %) developed septic shock. mean sofa on the day of stenotrophomonas maltophilia infection was ± . prior antibiotic use was observed in % including an antipseudomonal agent in % of cases. infection due to stenotrophomonas maltophilia was considered in cases. empiric antibiotic therapy was administered to patients ( %) and had included an appropriate agent in only five cases ( %). after adapting antibiotics, monotherapy was the choice for six ( %) patients while a combination of two antibiotics was indicated in the others ( %). the most used antibiotic was the colistin in episodes ( %). intensive care mortality was %. univariate comparison between dead and survivors showed a significant difference in prior nosocomial infection and respiratory comorbidities. no independent risk factor of mortality was found in multivariate analysis. rationale: thrombocytopenia is a frequent disorder in critically ill patients, and several studies have reported its correlation with poor prognosis. considering the major role of platelets in hemostasis, a significant drop in platelet count is an alarming sign in septic patients. the aim of this study was to show the relationship between thrombocytopenia and platelet level changes and mortality in septic patients. patients with criteria for septic shock (based on the third international consensus definitions for sepsis and septic shock) at admission or at any time during hospitalization were included in a prospective study conducted for a period of months (january -august , ) in a medical surgical intensive care unit. patients hospitalized for less than h were excluded. thrombocytopenia was defined as a platelet count less than . /mm , and recovery was defined as returning to levels more than . /mm after presenting thrombocytopenia. we assessed the platelet count during the hospitalization and its outcomes. we included patients. the mean ± sd age was . ± . years. sex ratio was . . thrombocytopenia during sepsis (group ) was found in patients ( %) with a mortality rate at %. the mortality rate among patients not showing thrombocytopenia (group ) was significantly lower % (p = . ). the receiver operating characteristic showed that in (group ), a drop in the platelet count (from admission to septic shock day) more than % was associated with poor outcome (sensibility = %, specificity = %, auc = . ). among the (group ), % showed recovered platelet counts. the mortality was significantly higher in the patients with uncovered thrombocytopenia ( % vs. %, p = . ). conclusion: thrombocytopenia was shown to be an indicatorof poor prognosis in our study. in addition, drops of > % and failure to recover the platelet counts were further determinants of unfavorable outcomes. compliance with ethics regulations: yes. mehdi gaddas , sarra dhraief , karim mechri , imen jami , amenallah messaadi , lamia thabet rationale: pseudomonas aeruginosa is known as an opportunistic pathogen frequently causing serious infections. multidrug resistance in this bacterium is increasing worldwide and poses a major problem in the treatment of infections due to this microorganism. analysis of resistance profile to antibiotics of p. aeruginosa helps to establish a prompt control and prevention program. the aim of this study was to evaluate epidemiological profile and antimicrobial resistance of p. aeruginosa isolates in a trauma and burn center. patients and methods: retrospectively, we studied all p. aeruginosa isolates over a -year period (from january to december ). conventional methods were used for identification. antimicrobial susceptibility testing was performed with disk diffusion method and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. data were analyzed using the sirsystem. minimum inhibitory concentration of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may . results: during study period, non-repetitive strains of p. aeruginosa were isolated, representing % of all isolates. in our center, infections due to p. aeruginosa were endemic with epidemic peaks. p. aeruginosa was mainly isolated from burn intensive care unit ( . %) and anesthesiology department ( . %). the most frequent sites of isolation were skin samples ( . %), blood cultures ( . %), catheters ( . %) and urines ( . %). the survey of antibiotic susceptibility showed high percentage of resistance to the different antibiotics: . % of strains were resistant to ceftazidime, % to ticarcillin, . % to pipercaillin-tazobactam, % to imipenem, . % to ciprofloxacin and % to gentamicin. resistance to colistin was rare. it concerned only four strains, isolated from burn patients. the survey of antibiotic susceptibility evolution have shown a global increase of resistance to commonly prescribed antibiotics between and : from % to . % to imipenem, from . to . % to ticarcillin-clavulanate, from . % to % to ceftazidime and from . to % to gentamicin. whereas ciprofloxacin resistance rate have decreased from . to %. antibiotic resistant strains were mainly isolated from burn intensive care unit, with % of resistance to imipenem and . % to ceftazidime. the dissemination of multidrug-resistant strains of p. aeruginosa in our center must be contained by the implementation of strict isolation methods and better hygienic procedures. compliance with ethics regulations: yes. acinetobacter baumanii: therapeutic impasse sabah benhamza, mohamed lazraq, abdelhak bensaid, youssef miloudi, najib el harrar réanimation de l'hôpital du août, casablanca, morocco correspondence: sabah benhamza (benhamzasabah @gmail.com) ann. intensive care , (suppl ):p- rationale: acinetobacter baumanii (ab) is frequently responsible for nosocomial infection in the intensive care units, and its resistance to antibiotics continues to increase. the objective of our study is to determine the epidemiological profile and antibiotic sensitivity of isolated bacteria in the intensive care unit august , in order to optimize the probabilistic antibiotherapy of bacteremia in intensive care. patients and methods: this is a retrospective study performed in the intensive care unit of the hospital august , , spread over a period of years from january to january . results: the incidence of ab infection in our department was . % for all patients admitted to intensive care. the average age was years ± , male predominance (sex ratio . ). the average time to onset of infection was days. during the study period, ab strains were isolated, % of which were pulmonary, % blood, and % urinary. resistance to c g reached % in , % in and % in . for imipenem resistance was % in , % in , % in . for amikacin, resistance was % in , % in , and % in . for fluoroquinolones resistance was % in , % in and % in . cotrimoxazole resistance was around % in the last years conclusion: the resistance of ab to antibiotics has reached very alarming levels, especially for carbapenems. this requires resuscitators to change their antibiotic prescription behavior and to invest in the prevention of nosocomial infections. compliance with ethics regulations: yes. this is a prospective observational study conducted at the ed during the period of year. data of all patients admitted with suspected infection of any cause were collected. poor outcomes were defined as death and transfer to an icu within h. results: during the study period, a total of patients with a mean age of ± were included. % were male. within h of management in the ed, % of patients were transferred to the icu and % died. independent predictors of icu-transfer and death included low systolic blood pressure, fever and tachycardia. a prediction model containing these independent predictors had a good predictive accuracy with an area under the curve of . ( % ci . - . ). sensitivity was %, specificity %, positive predictive value % and negative predictive value %. conclusion: assessing readily available clinical variables at arrival to the ed can aid in predicting poor outcomes. [ ] [ ] [ ] [ ] [ ] [ ] . the most common co-morbidities were chronic respiratory failure (crf, n = ) and hypertension (n = ). respiratory distress (n = ) and coma (n = ) were the major indications for iv. us diaphragmatic exploration was performed at a median delay of iv at days [ ] [ ] [ ] [ ] [ ] [ ] . % of patients received sedation and . % received neuromuscular blockers. the ventilator mode was control volume in patients via endotracheal tube (n = ) and tracheostomy cannula (n = ). no major incident was detected during the turning of patients. both tid and ted decreased from the sp to the pp (fig. ) : tid (mm) ( in sp vs. . in pp, p = . ), ted (mm) ( . in sp vs. in pp, p = . ). the observed dtf was lower in the pp but without significance ( . vs. . %, p = . ). no difference was showed when the comparison between sp-dtf and pp-dtf was adjusted on the ventilator mode, obesity, neuromuscular blockers and crf. the positioning in pp in ventilated patients reduces both tele-inspiratory and tele-expiratory diameters of the diaphragm but not altered its contractile function. compliance with ethics regulations: yes. significance was considered at p < . . results: results are presented in the table below. discussion: nebuliser type influences the efficiency of aerosol delivery, with the vmn delivering a significantly higher % aerosol dose than the jn at the two circuit positions (p = . on inspiratory limb; p = . at the dry side of humidifier). in agreement with previous reports using bias flow, for both nebulisers, the location within the circuit has a significant effect, with the nebuliser on the dry side of the humidifier delivering more aerosol than on the inspiratory limb (p = . for vmn; p = . for jn). conclusion: for a mechanically ventilated adult tracheotomy patient, the type of nebuliser and the location of the nebuliser within the circuit influences aerosol delivery. rationale: automatic tube compensation (atc) is a mode available in most icu ventilators. it compensates for the resistive pressure into endotracheal tube/tracheostomy canula by continuously providing a pressure assistance based on internal diameter of a new endotracheal tube/tracheostomy tube. its use in icu is unclear. we designed a survey to further explore this. patients and methods: the survey was endorsed by the acute respiratory failure section and the clinicaltrials group of the european society of intensive care medicine (esicm). the pool was sent out via an email on june to the esicm members worldwide. the following closed questions were: country, years in icu, kind of icu, kind of hospitals, kind of respirators, atc use (never, always or in some patients), reasons to or not to use atc, ventilatory mode in which atc was used. the database was frozen on august st after two reminders. we used the gross national income per capita (usd) provided by the world bank to transform the respondent's country into a geographical-economical variable with levels: high-europe, high-noneurope and middle ( ) . atc use was coded as yes or no. the primary end-point was atc rate of use and the hypothesis was that less than % of the respondents do use it. variables were expressed as counts. groups were compared by chi square test. a logistic regression analysis was performed to explore the contributing factors to atc use. we received responses without any doublons, of which six were empty, from countries. four-hundred and nine respondents used atc always or in some patients ( % atc rate of use). this rate was not different between economical-geographical regions, icu, hospitals and years in icu. for those respondents who did not use atc the reasons were: atc mode not available in icu ventilators ( . %), atc not helpful mode ( . %), atc not known ( . %) and atc provides too much pressure assistance ( . %). for those respondents who used atc the reasons were: helpful in weaning ( . %), set by default ( . %) and physiological benefit ( . %). they used atc during spontaneous breathing trial ( . %), with any assisted mode ( . %) and with specific modes ( . %). we found no risk factor for atc use in the logistic regression model (fig. ) . the atc rate of use was unexpectedly high in this survey. this may result from respondents selection bias or from an a priori underestimation of its use. compliance with ethics regulations: yes. rationale: during pressure support ventilation (psv), adjusting the level of assistance mainly aims at maintaining the patient's respiratory effort within a normal range. however, respiratory effort measurement is impeded in clinical routine by the need of esophageal pressure recording. in this study, we evaluated the accuracy of assessing the respiratory effort from the flow and airway pressure signals using several machine learning algorithms based on the equation of motion of the respiratory system. patients and methods: using the asl simulator (ingmar medical) connected to a pb ventilator (medtronic) set in psv, we simulated a massive number of different respiratory cycles. each simulated cycle represented a unique combination of compliance and resistance of the respiratory system, duration and intensity of the muscle pressure (pmus), positive end-expiratory pressure (peep) and pressure support levels. using least squares regression methods, the flow waveform was fitted according to the equation of motion of the respiratory system to determine the compliance and resistance of the respiratory system, and the pmus. the hypothesis used (alone or in combination) to constrain the system were: linearity of pmus at the onset of the inspiratory effort, nullity of pmus at the end of insufflation, and nullity of pmus during expiration. thus, nine methods were built and tested. calculated and actual peak pmus values were compared using the bland-altman method. the nine methods of pmus assessment were evaluated using different simulated cycles. by limiting the analysis to selected cycles with a predefined applicability criterion (intrinsic peep less than cmh o), a limited inspiratory effort (peak pmus less than cmh o) and a high quality of fitting (r > . ), the method using the three hypothesis together to constrain the system was characterized by a bias of . cmh o and limits of agreement of - . and . cmh o. however, when widening the analysis to all the simulated conditions, no method allowed an accurate estimation of the peak pmus : the best one exhibited a bias of - . cmh o and limits of agreement of − . and . cmh o. conclusion: among the nine machine learning methods tested, some provided an accurate estimate of the respiratory effort in selected cycles but none allowed such accuracy across all simulated conditions. this incites to assess automated methods using a more complex physiological and physical model. compliance with ethics regulations: not applicable. rationale: there is a growing interest in esophageal pressure monitoring in mechanically ventilated patients. esophageal pressure can be measured with a specific nasogastric catheter equipped with esophageal balloon and connected to a pressure transducer. it is used as a surrogate for pleural pressure and may be considered as a corner stone in advanced care of ventilated patients to better assess lung and chest wall mechanics and easily detect patient-ventilator asynchronies. however, this promising technique is still seldom used in clinical practice. trained icu nurses may perform oesophageal pressure measurements which may help facilitate its implementation in the usual patient care. this study aimed at assessing whether a specific educational program to train nurses to perform esophageal pressure monitoring allowed reliable measurements. this was a prospective monocenter study performed in an academic icu. written informed consent was obtained from the nurses before inclusion in the study. the specific educational program consisted of a -min online theoretical course, a -h group theoretical teaching and a -min simulation training on a mannequin. then each participating nurse performed three esophageal pressure measurements (using nutrivent ® catheters and an icu monitor connected to arterial line pressure transducers system) on three different mechanically ventilated paralysed patients under supervision. a knowledge assessment was performed with a short written mcq test. the skill evaluation was by two trained experts. concretely the trained nurses performed an esophageal pressure measurement without assistance. their ability to control the esophageal balloon position by an occlusion test, to measure the inspiratory and expiratory airway and transpulmonary pressures and to calculate of respiratory system, lung and chest wall compliances was assessed at the bedside using a standardized evaluation form. we present here the preliminary results of the first nine included nurses. the written knowledge assessment was considered as rationale: several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation. we conducted this study to compare t-piece and pressure support ventilation (psv) ( cmh and peep ) in the process of weaning of mechanical ventilation in burns. patients and methods: it was a prospective randomized trial in burn icu in tunisia during months. mechanically ventilated patients who met standard weaning criteria were included [ ] . patients were randomized into two groups: group under t-piece and group under psv. duration of the test: - min. the tolerance of the vs test should be judged on clinical criteria. stopping the test if occurred: agitation, tachypnea > cycles/ min, tachycardia > / min, spo < %. successful withdrawal was defined as the ability to maintain spontaneous respiration for h after extubation. results: thirty patients were included, randomized into two groups. the mean age was ± years with a ratio sex of . the average tbsa was ± %. the cause of mechanical ventilation was essentially a face neck burned ( %). the following table shows the weaning outcome of both modalities. eighty percent of succeeded extubation for both groups (n = / ). the cause of failure of extubation was secretion retention and clutter in majority of cases followed by neurological and cardiac distress. the duration of mechanical ventilation does not influence the outcome of the weaning test (p < . ), with a mean of duration of ± days. conclusion: our study did not show any difference between the two weaning modalities in the matter of outcome of extubation. the choice of weaning test of mechanical ventilation is to be judged by the clinician according of the state of his patient. compliance with ethics regulations: not applicable. rationale: when expiratory tidal flow does not go up after increasing expiratory driving pressure expiratory flow limitation (efl) occurs. it is thought that efl heralds airway closure (ac). we investigated the role of chest wall elastance (ecw) in both efl and ac in acute respiratory distress syndrome (ards) patients. our hypothesis was that the lower the ecw to lung elastance (el) ratio the higher the likelihood of efl and ac. patients and methods: twenty-five moderate to severe ards patients were prospectively included in two centers. mechanical ventilation was delivered in volume-controlled mode with tidal volume ml/kg predicted body weight at positive end-expiratory pressure cmh o in semi-recumbent position. airway (paw) and esophageal (pes) pressures and flow were continuously recorded during min by a data logger (biopac ). then, end-expiratory and end-inspiratory occlusions were performed for s, then respiratory system was slowly inflated at constant flow. finally, patient was allowed to breathe out freely to atmosphere by using a three-way stop lock by-passing expiratory valve. ac and airway opening pressure (aop) were determined according to chen et al. ( ) . efl was assessed by the atmospheric method ( ) . dynamic elastance of chest wall (edyn,cw) and lung (edyn,l) were obtained from least square linear regression method over consecutive breaths. static elastance (est,cw and est,l) were determined by classic formulas and also by taking into account aop (est,cw_aop and est,l_aop, respectively). the performance of ecw/el ratio to predict efl and ac was assessed by the area under receiver operating characteristic (aucroc) curve. results: efl was observed in patients ( %) and ac in ( %). median aop was . cmh o ( % ci . - . ) . aucrocs for ecw/el ratios to detect efl and ac are shown in table . edyn,cw/edyn,l ratio was better to detect efl than est,cw/est,l ratio with edyn,cw/edyn,l ≤ . % sensitivity and % specificity. correction for aop made the performance of est,cw/est,l ratio as good as that of the edyn ratio. ac was poorly predicted by edyn and est ratios but its prediction greatly improved with aop correction. however, with the est,cw/ est,l_aop the critical ratio was . (sensitivity %, specificity %) and . (sensitivity and specificity %) for predicting efl and ac, respectively. conclusion: efl and ac are frequent in ards at peep cmh o. edyn,cw/edyn,l ratio lower than best predicted efl occurrence. once ac is taken into account est,cw/est,l ratio greater than accurately predicts ac. efl and ac are two distinct phenomena. compliance with ethics regulations: yes. rationale: anesthesia outside the operatingroom (aoor) in a pediatric environment was giving increasingly increasing indications and a lot of progress because of its interest in carrying out diagnostic and/or therapeutic explorations: % of the acts of anesthesia are performed outside the operating room. the objective of our study is: to clarify the importance and the frequency of the practice of the ahbo, to define its particularities, as well as an evaluation of the ratio: benefit/risk in order to reduce the morbidity and mortality. patients and methods: we report in this study the experience of the service of the resuscitation mother-child on the gestures of aoor. this is a prospective observational study, spread over a period of months: from / / to / / , dealing with acts performed for endoscopic digestive and bronchial procedures, cures in dermatology and radiotherapy, and medical imaging (ct and mri). results: of the procedures performed: were performed for ct, for mri, for arteriography and for endoscopic digestive procedures, for bronchoscopies, for radiotherapy treatments, for laser treatments in dermatology. anesthesia techniques use intravenous induction in % of cases using: hypnotics (propofol, midazolam, ketamine), morphine (remifentanyl, fentanyl), inhalation induction in % of cases (sevoflurane, halothane) and curare for cases of bronchoscopy (rocuronium). this anesthesia was marked by the occurrence of accidents in order of frequency: cardiac in % of cases (tachycardia, hypotension and rhythm disorders), and then respiratory in % of cases. the most serious accidents were admitted in reality and are represented by cases, of which required an intubation (bronchoscopy), a case of cardiorespiratory arrest recovered, cases of severe hypoxia associated with bradycardia and which required the ventilation with the mask (radiotherapy), and cases of bronchospasm requiring the deepening of the anesthesia (absence of tci). a good knowledge of the patient and the intervention, and difficulties specific to each specialty is necessary, as well as a preanesthetic consultation. the aoor must obey the same safety rules as in the operating theater and that in terms of: equipment, monitoring (integrate the capnograph to respiratory monitoring whenever deep sedation and when the continuous control of vas is difficult), anesthetic technique (tcbi) and post-procedure wakefulness management that must meet the same requirements as the sspi, especially for prolonged sedation. compliance with ethics regulations: yes. umbilical vein catheterization through wharton's jelly: a possibility for a fast and safe way to deliver treatments in the delivery room? suzanne borrhomée hôpital rené dubos, france correspondence: suzanne borrhomée (suzanne.borrhomee@gmail. com) ann. intensive care , (suppl ):p- rationale: a fast and safe venous access can be a critical issue in the delivery room during neonatal cardiopulmonary resuscitation, or before endotracheal intubation. here, we describe a new method to inject drugs using the umbilical vein, directly punctured through wharton's jelly. this method was performed in newborns between november and may . umbilical vein was identified and punctured easily and a reflux was obtained in all patients. the first step was antisepsis, and then the umbilical vein was punctured. the puncture was made approximately to cm above the navel. after checking for blood reflux, the nurse injected the treatment. the cannula was left in the vein during the injection and removed as soon as the intervention was over (intubation was performed, or the heart rate had increased). results: here, we report ten cases of emergency injection in the delivery room using this method: -four cases of cardiopulmonary resuscitation using this method to deliver epinephrine. cardiac massage was performed on all patients.-six cases of intubations in the delivery room using this method to administer the premedication. in all patients, the umbilical vein was identified easily. the equipment was the one usually used for venous injection in our unit and was manipulated and handled with ease. venous access was obtained in a matter of seconds, and blood reflux was observed in all patients. the treatments were efficient in all but two patients, which was imputable to the method in one patient. discussion: although this method has been known in our nicu for several years, there has been no publication regarding this method in neonates. inserting an umbilical vein catheter in the delivery room has been validated for resuscitation but this technique is lengthy and requires some sterility conditions that makes it even longer, and thus non-fitting for an emergency tracheal intubation. our method is fast and can be performed easily with no specific training. the whole manipulation procedure, from the beginning of the puncture to the end of the flush-out takes to s. we only identified few specific risks related to this method, mostly infectious, and the risk of drug diffusion. we describe a new route for administration of drugs in the delivery room that was successfully used in nine neonates. umbilical vein needle catheterization is not only safe and efficient, but is also fast and easy to perform without any special training. compliance with ethics regulations: yes. rationale: liver transplantation (lt) is the only option for children with end stage liver disease. recent advances in surgical procedure and immunosuppression have permitted a better patient and long term graft survival. however, acute cellular rejection remains a frequent complication occuring in to % of the cases according to different studies. it is more likely to occur during the first weeks post lt. many predictive factors of acute rejection have been described in litterature and results differ from one study to another. pediatric studies regarding this topic are few. the aim of this work is to study acute cellular rejection prevalence in the days following lt and to determine predictive factors. rationale: sedation practices for pediatric magnetic resonance imaging (mri) are highly heterogenous. the main challenge is to keep children immobile while being alone in a traumatizing environment for a long time. clinicians have to ensure hemodynamic and respiratory stability in this isolated environment while minimizing sedation neurologic adverse effects. in this series, we report the potential usefulness, feasibility, efficacy and safety of dexmedetomidine sedation for pediatric mri. patients and methods: a single center retrospective review of six children sedated with dexmedetomidine for mri in an emergency context. all children were hospitalized in the pediatric intensive care unit of a university hospital at the time of mri. results: data on six patients aged months to years is reported. five patients received dexmedetomidine by intravenous route (bolus of - µg/kg over min, followed by a continuous infusion of µg/ kg/h). one child received dexmedetomidine by intranasal route ( µg/ kg with atomization device). one child experienced bradycardia that did not require any intervention. very few movements were recorded during the mris for which images were rated as good quality. conclusion: dexmedetomidine seems a promisingly useful sedation agent for pediatric mri, thanks to its efficient sedative properties and good tolerability without respiratory compromise. compliance with ethics regulations: yes. rationale: computational models, or virtual patients, could be used to teach cardiorespiratory physiology and ventilation, determine optimal ventilation management as well as forecast the effect of various ventilatory support strategies. currently, there is no virtual patient specifically designed for modelling children cardiorespiratory system. thus, our research team has developed a cardiorespiratory simulator for children called "simulresp©". according to summers et al., the quality of a physiologic model is evaluated by three specific criteria: qualitatively, which relates to the model's ability to provide directionally appropriate predictions; quantitatively in steady states and in dynamics, which is the ability of the model to provide accurate predictions in steady state situations as well as dynamic transitions. the purpose of this study was to evaluate the quality ofsimulresp© according to these criteria. this study consisted in a prospective evaluation of the simulresp©'s predictions with simulated healthy subjects. the tests were performed with patients from to years old ( , , , , , years), with different characteristics; gender (m, f) and weight ( th, th and th percentile). blood gas values (ph, pco , po and spo ) were simulated for several virtual healthy patients with different characteristics. this study was conducted for both spontaneously breathing and mechanically ventilated patients. simulresp©'s quality and reliability were evaluated in terms of accuracy, robustness, repeatability and reproducibility. results: simulresp©'s validation procedures are ongoing. we intend simulresp© to be accurate when simulating healthy spontaneously breathing patients. but we hypothezised that simulresp© would not be able to simulate accurate blood gas values of mechanically ventilated patients conclusion: simulresp© is a promising computational model that will serve to perform calibration and validation procedures of clinical decision support systems and help clinican to determine optimal respiratory support strategies at bedside. further calibration procedures are yet required. compliance with ethics regulations: yes. the isthmic surgical tracheostomy, which was performed in the operating room by otolaryngologist under general anesthesia. the cutaneous incision was transversal in all cases.the choice of the cannula was adapted to the age, and the decanulation was carried out according to the evolution of the underlying disease. complications associated with tracheotomy are diverse, and common complications are such as careassociated pneumonia ( . %), tracheostomy tube obstruction ( . %), accidental decannulation ( . %), pneumothorax ( . %) and cases of tracheal stenosis ( . %). the mortality rate amounted to . %, where in most cases was due to the poor prognosis of the underlying diseases. the main factors of evolution are the patient's previous condition, cranial trauma, guillain-barré syndrome, tracheostomy time, prolonged tracheal intubation and the presence of complications. conclusion: regardless of the indication, the tracheotomy is an act of survival whose usefulness and effectiveness are certain. rationale: aspiration pneumonia (ap) is a frequently suspected complication of drug overdose requiring mechanical ventilation (mv) and admission to intensive care unit (icu). in the absence of reliable biomarkers for distinguishing between aspiration pneumonia and aspiration pneumonitis, antibiotic therapy is frequently prescribed. latest studies suggest that a care protocol could better select patients requiring antibiotic therapy. the objective was to determine the impact of a care protocol on the antibiotic prescription among patient admitted to icu for toxic coma with mv. we conducted a prospective observational cohort study in four icu. we included all patients admitted for toxic coma with mv. in the university-affiliated icu, a care protocol was applied. in the three others icu, physicians declared that they did not follow formalized conduct within the service and did as usual. results: we included patients in care protocol group and in control group. the mean saps ii was . (± . ) with a mean glasgow coma scale score at . (± . ) before intubation. within the total population, patients ( %) had a pulmonary bacteriologic sample (pbs), mostly because purulent tracheobronchial aspirate and new infiltrates on the chest x-ray (respectively . % and . % of the population with a bacteriological sample). among the patients with a bacteriological sample, ( %) were culture positive. the incidence of probabilistic antibiotherapy did not differ between the care protocol group (n = ) and the control group (n = ) . there was no difference for the incidence of pbs ( in each group). the others secondary outcomes did not differ either (table ) . conclusion: our study does not show that a care protocol allows a reduction of antibiotic prescription among patient admitted to icu for toxic coma with mv. our incidence of antibiotic prescription is lower than the previous studies. the absence of difference can be explain by two reasons: some of the physicians of the control group had been trained in the university-affiliated icu in the last years and may follow a management approach similar to that of the control group; despite our precautions, the existence of the study could have modify the practices in the control group. compliance with ethics regulations: yes. rationale: pancreatic surgery is associated with high morbidity, mostly due to infectious complications, so that many centers introduce post-operative antibiotics for all patients. such systematic prescriptions are not consensual and often rely on local practices. the aims of the study were to describe the occurrence of surgical site infection (ssi) and the antibiotic (atb) prescription after pancreatic surgery, and to determine the risk factors of post-operative surgical site infection, in order to better define the clinical indications for the prescription of antibiotics after major pancreatic surgery. patients and methods: all patients undergoing a scheduled major pancreatic surgery from january to november were included in the study. patients were classified in four groups according to the occurrence of a surgical site infection and to the post-operative antibiotic prescription as follows (ssi+/atb+; ssi-/atb+; ssi+/atb-, ssi-/ atb-). in addition, risk factors (fever and pre-operative biliary prosthesis) associated with the occurrence of a surgical site infection and with the antibiotic prescription, were analyzed using a logistic regression model. results: data from patients ( pancreaticoduodenectomies and splenopancreatectomies) were analyzed and classified as presented in the table. thirty patients ( . %) experienced a surgical site infection and ( . %) received post-operative antibiotics. we did not find any difference on post-operative antibiotic prescriptions ( . % versus . %, p = . ) between patients who developed a surgical site infection and those who did not. amongst the patients who were not prescribed antibiotics post-operatively, ( . %) did not develop a surgical site infection while ( . %) did. in-icu mortality did not differ between infected and non-infected patients ( versus %, p = . ). post-operative fever was different between ssi+ and ssi-( . versus . %, p < . ), while the prevalence of pre-operative biliary prosthesis was similar ( . versus . %, p = . ). amongst patients who did not develop a surgical site infection, antibiotic prescription was not associated with fever (p = ), but associated with a higher prevalence of preoperative biliary prosthesis ( . versus . %, p = . ). conclusion: non-systematic antibiotic prescription after major pancreatic surgery allowed to appropriately spare antibiotics in ( %) patients at the cost of under prescription in ( . %) patients. these results suggest that systematic post-operative antibiotic prescription could be excessive. fever appears to be a relevant clinical sign for individual-based prescription, whereas the presence of a biliary prosthesis does not. compliance with ethics regulations: yes. ( , ) . however, there is little evidence to support those recommendations ( ) . we aimed to describe care paths of pm with sepsis in french hospitals and to assess outcomes depending on their hospital trajectory. we conducted a retrospective analysis of the french medico administrative (pmsi) database of consecutive patients with pm and sepsis admitted to french hospitals, between and . only the first hospital admission was considered. cases were identified using a combination of a diagnosis code for pm plus a diagnosis code for organ failure or a procedure code for organ support. hospital trajectories were determined from the first admission to death or discharge, taking into account all potential transfers. costs and endpoints were determined at the end of patients' trajectories. five groups of patients were defined, according to care pathways: direct icu admission ( sticu); secondary icu admission, after initial admission to another unit including wards (ward ndicu) rationale: new-onset atrial fibrillation (af) is a common complication in patients with sepsis and is associated with increased mortality and morbidity rates. this condition results from a complex chain of events in response to infection, involving immunologic, humoral and cellular process and sympathetic overactivity. landiolol, the new injectable beta-blocker, with high beta selectivity and minimal impact on arterial blood pressure, may have beneficial effects in such a context. in this study, we aimed to investigate whether landiolol decrease the newonset of atrial fibrillation in a mice model of endotoxin-induced sepsis. patients and methods: thirty c bl/ male mice were randomly allocated to the following groups: sham (administration of µl of isotonic saline intraperitoneally-ip), septic (administration of µl of isotonic saline with mg/kg of lipopolysaccharide-lps-of e. coli o :b ip) and septic + landiolol (administration of isotonic saline with mg/kg of lps and, two hours later mg/kg of landiolol ip). four hours later, an attempt of af occurrence was triggered by a transesophageal electric pacing at fixed rate (as previously reported) in all mice previously anesthetized by isoflurane %. ekg was continuously recorded. results: ten mice per group (mean weight: ± g) have been included and analyzed. among the sham group the mean heart rate was at bpm versus bpm in the septic group. among the septic + landiolol group the mean heart rate was at bpm (p < , ). after transesophageal stimulation, none mice in the sham group had af, seven mice ( %) in the septic group had an af, and mice ( %) in the septic + landiolol group had an af. landiolol decreased the incidence of new-onset, sepsis-induced atrial fibrillation in mice (p = . ). conclusion: landiolol seems to have a protective effect against sepsis-induced af in mice. however, the mechanisms, including sympathetic activation and inflammasome pathways, should be investigated before drawn definitive conclusion regarding to efficiency of landiolol to prevent new-onset af during sepsis. compliance with ethics regulations: yes. - mg/l at or h, proportion of patients with a vancomycin serum concentration < mg/l, previously associated with resistance emergence and assessment of mortality and test of cure. results: a serum vancomycin concentration between - mg/l was reported in out of included patients ( %). a serum vancomycin concentration < ml/l and > mg/l were reported in patients ( %) and patients ( %), respectively. vancomycin serum concentrations during follow-up are shown in fig. . in multivariate regression analysis, a longer time between admission and initiation of vancomycin was the only parameter associated with a serum vancomycin out of this target, while acute kidney injury (aki) was associated with a lower incidence of subtherapeutic concentration. acute kidney injury rate was significantly higher in patients with a serum vancomycin concentration > mg/l. discussion: an adequate therapeutic target of serum vancomycin concentration was reached in % patients with nearly % < mg/l, which was similar to previous studies. aki and rrt requirement were higher in patients with serum vancomycin concentration > mg/l, whereas it is hardly to know whether it is a cause or a consequence. conclusion: these findings highlight the importance of a larger loading dose, vancomycin monitoring and measured creatinin clearance to improve vancomycin dosing protocol. compliance with ethics regulations: yes. rationale: suicide is a global phenomenon and one of the leading causes of death in the world. tunisia ranks second in the suicide rate in the maghreb, with . cases of suicide per , inhabitants. the aim of this study was to reconstruct the state of suicidal subjects before the act in order to identify their psychiatric profile. patients and methods: a -year prospective observational singlecenter ( -bed intensive care unit) study including all patients hospitalized for suicide attempt (sa). psychiatric evaluation of patients and contact with their families were done before intensive care unit discharge. results: seventy-one patients were enrolled with female predominance (sex ratio . ). mean age was ± years. familial or personal history of mental illness were found in ( %) and cases ( %) respectively. personal mental disorders were depression ( %), bipolar disorder ( %), schizophrenia ( %) and border line personality disorder ( %). twenty-five per cent had prior sa. sixty-three per cent were single, % married and % divorced. the common methods of suicide included drug ( %), chloralose ( %) and pesticide ( %) poisoning. mean igs ii and apache ii scores were ± and ± respectively. on admission, % of all patients were in coma, % had shock and % developed aspiration pneumonia. mechanically ventilation was done in % of all cases with mean duration of days. the mean length of stay in intensive care unit was days. mortality rate was %. psychiatric evaluation and contact with families deduced that the main precipitating factors for suicide were traumatic events. in fact: relationship problems (familial, marital or breakups), school failure and mourning were found in %, % and % of all cases respectively. reactional sa accounted for %. rationale: poisoning is a worldwide problem, associated with high morbidity and moratlity. in tunisia, the rate of fatal poisoning has been increasing in the last years, with emergence of new toxic substances. regardless of the toxic, fatal poisining is considered as a non natural death, that requires medico-legal investigation, to assess whether it is suicidial, crimnal or accidental death. this study aimes to determine the epidemiological characteristics of the cases of fatal poisoning in south, to identify the toxics used in oder to deduce the preventive measures. patients and methods: we conducted a retrospective study of all cases of fatal poisoning recorded in the forensic department of habib bourguiba university hospital in sfax, tunisia, over a -years period ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . results: during the study period, cases of fatal poisoning were autopsied. the number of victims recorded per year varied between and cases with an average of cases per year. the average age was years with extrems ranging from months to years. nearly half ( . %) were younger than years. a male predominance was noted with a sex-ratio of . . the majority of victims were single, loweducated and from rural origin. personal antecedent of psychiatric pathology was found in . % of cases. psychotic disorders (schizophrenia) and depression were the most common pathologies. in our study we noticed that death occured every weekday without significant difference between days. however, the frequency of fatal poisoning was slightly higher in cold seassons ( . %). in . % of cases, victims were found dead at home. accidental fatal poisoning was the most common ( %). no criminal cases have been observed. we noted a male predominance in accidental forms and a female predominance in suicidal forms. carbon monoxide poisoning was the most common ( cases) followed by the organophosphorus poisoning which was noted in cases. conclusion: decreasing the mortality rate from poison ingestion requires increasing public awareness about poisons and improving emergency service equipment and health personnel training. compliance with ethics regulations: yes. severe acute poisoning by organophosphate pesticides: report of cases at the oran hospital and university center mourad goulmane hospital and university center of oran, oran, algeria correspondence: mourad goulmane (goulmane.mourad@univ-oran . dz) ann.intensive care , (suppl ):p- rationale: organophosphate pesticides are synthetic organic pesticides widely used in agriculture mainly as an insecticide, nemacid or acaricide. these are the agricultural products, the most incriminated in poisoning in our context. the objective of this work was to determine the clinical, paraclinical, and progressive characteristics of this poisoning in a resuscitation environment. patients and methods: retrospective study of cases admitted to intensive care (january -december ). inclusion criteria were clinical, para-clinical, therapeutic and progressive. results: cases were identified: women and men, mean age = . ± years. the suicide attempt was the main reason for the intoxication ( cases). the glasgow coma score averaged ± . the central syndrome was present in % of our patients, followed by muscarinic syndrome % and nicotinic syndrome in % of cases. therapeutic management consisted of mechanical ventilation in % of cases, the use of vasoactive drugs in % of cases and the administration of antidotal treatment in % of cases. the overall mortality was . %. conclusion: organophosphate pesticides intoxication is a real health problem in algeria. it is a serious condition dominated by the respiratory and neurological distress that causes most deaths. it concerns in our context especially young women who ingest the product for the purpose of autolysis. the diagnosis is based on the clinical and dosage of cholinesterase activity in the plasma. treatment combines symptomatic measures that rely primarily on respiratory and neurological resuscitation to antidotal treatment. the clinical course in this type of intoxication is generally favorable under treatment with regression of signs in a few days. mortality is high in our context, so it should be considered a diagnostic and therapeutic emergency. the commercial availability of these products is worrisome, justifying the use of a broad prevention program to inform the public and authorities of the danger of organophosphate pesticides compliance with ethics regulations: not applicable. . the clinical examination revealed that five patients met the criteria for serious intoxication with the following signs: coma in four patients requiring the use of mechanical ventilation, seizures (n = ), rhabdomyolysis (n = ), shock (n = ), toxic takotsubo (n = ) and hepatocellular failure (n = ) leading to patient's death. the use of mechanical ventilation was necessary in patients. the analysis of the severity factors did not show a statistically significant association between severity, age (p = . ), sex (p = ) and chronic consumption of psychoactive substances (p = . ). on the other hand, we did not find a statistically significant association between serious intoxication, the number of tablets ingested (p = . ), the apacheii score (p = . ) and the average length of stay (p = . ). conclusion: ecstasy acute poisoning is becoming more common in our country and can potentially be very serious regardless of age, sex, medical history or number of tablets ingested. on the other hand, the concentration of nmda could be the only factor to be taken into consideration upon admission. compliance with ethics regulations: yes. quarter of early trauma-related mortality, in some series. early identification of poor outcome predictors could be valuable to guide the most appropriate care. we aim to determine factors associated to mortality in patients with severe non-penetrating chest trauma admitted to the icu. patients and methods: this is a prospective cohort study, including all patients with isolated severe blunt chest trauma (abbreviated injury scale ais > ) admitted to the intensive care unit of a university hospital, over a one-year period. the primary objective was to analyse risk factors associated to death and poor outcome using univariate and multivariate analysis. results: one hundred-thirty patients were admitted to the icu for blunt chest trauma among them were diagnosed with severe isolated chest trauma and were included. the mean age was at ± , mean iss at ± and mean tts at ± . twenty-eight ( %) patients were diagnosed with acute respiratory distress syndrome, ( %) with post-traumatic acute kidney injury and fourteen ( %) with post-traumatic pulmonary embolism. the mean length of icu stay (los) was at ± days and mean number of days on ventilator was at ± days. thirty-two ( %) patients underwent elective tracheostomy for prolonged intubation. thirty-seven patients ( %) developed infections, among them thirty ( %) were diagnosed with pulmonary infection and seven ( %) with non-thoracic infections. overall mortality had an incidence of . % ( patients rationale: early hyperglycaemia in traumatic brain injury (tbi) is a part of the stress response. it is an important indicator of severity and a reliable predictor of prognosis. we aimed to describe the epidemiological, clinical and paraclinical characteristics and to assess the prognostic impact of this hyperglycaemia on the tbi. we conducted a retrospective study in the intensive care unit (icu) of our hospital between and . were included all patients with tbi and blood glucose > mmol/l at the first h post-trauma. results: during the study period, patients were hospitalized in our icu with tbi. early hyperglycemia (> mmol / l) was found in patients ( . %). in univariate analysis, glycaemia > . mmol/l (= mg/dl) at admission was significantly associated with mortality (p = . ). we observed that glycaemia > . mmol/l at h , > . mmol/l at h , > . mmol/l at h and > . mmol/l at h was significantly associated with mortality (p = . ; p < . ; p = . and p = . , respectively). the risk factors significantly associated with mortality were age > years (p < . ), saps ii > (p < . ), initial shock (p < . ), glasgow coma scale (gcs) < / (p < . ), coma period > days (p = . ). the ct scan lesions statistically associated with mortality were: subdural hematoma (p < . ), cerebral oedema (p < . ), intra cerebral haemorrhage (p = . ), cortical contusion (p = . ), contusion of cerebral trunk (p = . ), contusion of the corpus callosum (p = . ), thalamus contusion (p = . ). in multivariate analysis, independent risk factors statistically associated with mortality were age > years old (or = . ic [ . - . ]; (p = . )), glycaemia > . mmol/l at admission (or = . ic [ . - . ]; (p = . )),gcs < / (or = . ic [ . - . ]; p < . ), intracerebral hematoma (or = . ic [ . - . ]; p = . ). we recommend a mandatory control of the blood glucose levels during a tbi with a target between . and . mmol/l in the acute phase. compliance with ethics regulations: not applicable. the fat embolism syndrome (fes) is a set of clinical, biological and radiological signs resulting in the obstruction of microcirculation by micro-droplets of insoluble fats.the clinical signs of the fes are not very specific, the diagnosis is difficult and the risk of misunderstanding this syndrome is very real.the fes appears after a trauma, often few days later. however, it sometimes occurs without previous trauma; and it is particularly difficult to recognize in these cases. the aim of this work is to define the epidemiological profile, the clinical and para-clinical features of this syndrome and its therapeutic management. rationale: sedative and analgesic treatment administered to critically ill patients with mechanical ventilation need to beregularly assessed to ovoid complications of oversedation mainly in elderly patients. our objective is to evaluate our sedation practice in the elderlyin our unit patients and methods: it was a prospective observational study, including elderly patients over years of age without acute brain injury requiring sedation more than h of hospitalization in the intensive care unit of our university hospital between april and december . thirty patients were included. the aged was . years, the sex ratio was . . respiratory distress was the most common reason for hospitalization %. the most accepted diagnoses were the decompensation of copd in % of cases and septic shock in % of cases. the saps ii averaged ± points, sofa averaged ± . points. renal failure was found in patients ( %), hepatic impairment was noted in patients ( %), hypoproteinemia was marked in patients ( %). midazolam was used in % of patients. it was in combination with fentanyl in % of cases and remifentanyl in % of cases. the median ramsay score . ± . on the first day of sedation and . ± . on the second day of sedation. the median rass scale was − . ± . on the first day of sedation and − . ± . on the second day of sedation. the median bps scale . ± . on the first day of sedation and . ± . on the second day of sedation. the mean wake up time was ± , days. neuromyopathy of resuscitation was suspected in seven patients ( %), withdrawal syndrome was observed in two patients ( %) and acute cognitive dysfunction in two patients ( %). the median duration of sedation was . days ± . days, the median duration of mechanical ventilation was . ± . days, the median length of stay was . ± . days. ventilator-associated pneumonia was diagnosis among % of patients. the mortality in intensive care was %. conclusion: sedation analgesia in the elderly person should be adapted according to age, ideal weight and renal and hepatic function by decreasing the initial doses. it should be evaluated by the recommended scores by setting a sedation objective according to the pathology. compliance with ethics regulations: not applicable. rationale: more than original articles are newly indexed in pub-med every day. journal club (jc) is one way to cope with this abyssal amount of medical information. we aimed at ( ) describing journals and articles analyzed during our jc sessions ( ), reporting the proportion of published articles being analyzed during jc sessions and ( ) assessing the clinical impact on our daily practices for each journal. patients and methods: a retrospective analysis of prospectively collected data over a -year period from to in a universityaffiliated icu. jc sessions were scheduled weekly and participants were free to choose and expose orally an article recently published in any medical journal (general, icu or non-icu specialized). clinical impact of a journal was retrospectively and independently assessed by two attending intensivists (dc, hm) and was defined by the ratio of articles considered as having a direct impact on our daily practices over the number of articles of the same journal read during the same period. results: from august to august , jc sessions were held and articles-mostly original (n = / ; %)-from journals were analyzed, accounting for . % of the articles ( . % of the original articles) referenced in pubmed during the same period. median number of articles exposed per session was [ ] [ ] [ ] [ ] . median number of doctors attending each session was [ ] [ ] [ ] (attendings: [ ] [ ] , fellows: [ ] [ ] , residents: [ ] [ ] ). general, icu and non-icu specialized journals accounted for %, % and % of the exposed articles, respectively. most of the reported articles dealt with intensive care (n = , %) especially infectious diseases (n = / ; %), hemodynamics (n = / ; %) or icu-organization (n = / ; %). compared to general and non-icu specialized journals, the proportion of read-over-published articles was higher for icu-specialized journals ( . % vs. . % vs. . %, respectively; p < . ). among original articles, only ( . %) [interventional (n = / ; %); observational (n = / ; %) studies] were considered as having a clinical impact on our daily practices. compared to icu and non-icu specialized journals, general journals had a higher clinical impact ( . % vs. . % vs. . %, respectively; p = . ). data regarding the most read general, icu and non-icu specialized journals are detailed in table . in a french university-affiliated icu with regular jc sessions, the proportion of read-over-published articles and the clinical impact of medical journals appear minor. in the ocean of medical literature, general medical journals appear more worth reading by intensivists than icu-specialized journals. compliance with ethics regulations: yes. rationale: the world's population is aging and the and over's age group is growing fast (+ . % per year). this aging population is impacting intensive care units with exponential rates of elderly patients ( . % in , % in ) , associated with significant mortality (from % to %). the evolution and the prognostic factors of these elderly patients in intensive care are therefore a public health issue for optimal management. patients and methods: we included all patients aged and over who were operated and admitted to surgical resuscitation in our center, with a duration of stay greater than h, from april to july . the data collected were: general characteristics of this population, mortality in intensive care, at day and at months and the prognostic factors guiding their evolution in intensive care and at months. results: of the patients included in our study, mortality was . % in intensive care, . % at day and . % at months. the prognostic factors in the intensive care unit were the average dose of noradrenaline at day (threshold at . mg/h), the sofa score at day (threshold at points) and the igs score (threshold at points). the prognostic factors at months were ventilatory autonomy on day (spontaneous ventilation, non-invasive ventilation, invasive ventilation), the reason for admission to intensive care (acute respiratory distress or septic shock) and the fragility score (clinical failure scale with a threshold at ). conclusion: the mortality of patients aged and over is influenced by prognostic factors easily obtained daily at patient's bed. these prognostic factors could be an aid for the resuscitation teams to evaluate the relevance of the care undertaken in elderly or even very elderly patients admitted in an acute situation. compliance with ethics regulations: not applicable. assessing patient safety culture perception in the intensive care unit in tunisia oussama jaoued, chaoueh sabrina, sik ali habiba, wael chemli, gharbi rim, fekih hassen mohamed, elatrous souheil hôpital taher sfar, mahdia, tunisia correspondence: oussama jaoued (oussamajaoued@gmail.com) ann. intensive care , (suppl ):p- rationale: in tunisia health care system, patient safety has become a priority of quality assessment. the aim of our study was to describe the safety culture perception of the intensive care unit staff. patients and methods: the safety attitude questionnaire (saq-icu) was distributed to all intensive care unit staff by email. the questionnaire explores safety culture domains: "team work", "safety climate", "job satisfaction", "stress recognition", "perception of the hospital and intensive care unit management" and "work condition". results: eighty participants responded to the questionnaire, % of them were women. participants were doctors in . %. the coordination between physicians and nurses was very good only in %. thirtynine participants thought that the workload was high and % like their work. medical errors are handled appropriately in % of cases and it was difficult to discuss errors in % of cases. the hospital is a good place to work in % of participants, % of participants were less effective at work when there were tired. the hospital did a good effort of training new personal in % of cases. the number of medical staff was lower than expected in % of cases. half of participants would feel safe being treated as patients in their respective units. all domains explored by saq-icu could be improved according to attendants. conclusion: safety culture perception among intensive care unit staff had several deficiencies, mainly the working conditions, the ignorance of medical error reporting procedures and the lack of communication. rationale: the simplified acute physiology score ii (saps ii) is an icu scoring system used to predict the mortality risk in patients presenting at the icu. however the majority of critically ill patients present initially at the ed and their transfer to the icu may be delayed for hours. therefore, the ability to accurately assess mortality risk at ed may have a great impact. the purpose of this study was to evaluate the performance of saps ii in predicting early and late mortality in ed patients. patients and methods: this prospective study was conducted at the ed during a -month period. data for adult ed patients were evaluated. saps ii score was used to predict early and late mortality rates at -h and -day respectively. discrimination was evaluated by calculating the area under the receiver operating characteristic curve (auroc). results: during the study period patients were enrolled. the mean age was ± years, % of the patients were men. the mean saps ii was . the early mortality rate was % and late mortality rate was %. saps ii was efficient in predicting early mortality, with an auroc of . ( % ci . - . ). however, it demonstrated no value in predicting late mortality with an auroc of . ( % ci . - . ) conclusion: in this study, saps ii score was accurate in predicting early mortality, however this tool appears less suitable for predicting late mortality. compliance with ethics regulations: yes. oussama jaoued, chaoueh sabrina, sik ali habiba, yosri ben ali, fekih hassen mohamed, elatrous souheil hôpital taher sfar, mahdia, tunisia correspondence: oussama jaoued (oussamajaoued@gmail.com) ann. intensive care , (suppl ):p- rationale: the aging of the population increased the number of hospitalizations in icu. the aim of our study was to determine the impact of hospitalization of patients over the age of on morbi-mortality and consumption of care (omega score). patients and methods: this is a retrospective study carried out in the icu in the hospital of taher sfar in mahdia over a period of years. all patients hospitalized in the icu were included in this study. two groups of patients were individualized: g : patients over years old, g : patients under years old. results: during the study period, patients ( < years old and ≥ years old) with a mean age ± years and with a mean sapsii ± were included. the common reason for hospitalization was acute respiratory failure in % of cases. comparing the two groups, the severity score sapsii was higher among patients older than years ( ± vs ± , p < . ). the use of mechanical ventilation was more common in the first group ( % vs. %, p < . ). the incidence of nosocomial infections was similar in both groups ( % in the group g and % in group g , p = . ) and the use of renal replacement therapy was also similar in tow groups ( % in the g group and % in the g group, p = . ). the duration of mechanical ventilation and length of stay were similar between the two groups. workload evaluated by the omega score was higher in the first group ( rationale: icu outcome depends on quality of pre-icu care. we aimed to assess the chain of care of deteriorating ward patients (dwp), through evaluation of preadmission severity and delays before admission, and association with outcome. patients and methods: retrospective observational study in a single center ( beds general hospital) for year-may th of to . all adult patients admitted in the icu from the wards were included, except for scheduled surgery, or unexpected event in the operative theater. preadmission severity was assessed through levels of national early warning score (news ): group with news inferior to , group with news between and , and group with news superior to . these scores were established from vital signs during the h before icu admission. patterns of patients, including sofa and saps , knaus index, charlson comorbidity score, cause of admission and technics used in the icu, length of stay in the icu and in the hospital, limitations of life-supporting care, and mortality at and days after icu stay. satistical analysis was performed through chi and fisher tests on qualitative parameters, and with kruskal-wallis, student and mann-whitney tests for quantitave data. results: sixty-eight patients were studied: in group , in group and in group . most patients (all except ) had not respiratory rate monitoring before icu admission. icu mortality was associated with rising preadmission severity (group : . %; group : . %; group : . %). base patterns (charlson comorbidity score, knaus index) did not differ between the groups, and . % of patients presented with sepsis. main causes of admission were respiratory ( . %), hemodynamic ( %) or neurologic ( . %) failures. all patients admitted after cardiac arrest resuscitation ( patients) belonged to group . acute severity scores (sofa and saps ) followed preadmission severity. limitation or withdrawing of life support in the icu was higher in group ( . %) than in groups ( %) and ( . %) . median delay between first news equal or superior to and icu admission was h, and h between news equal or superior to . diffrences in delays were not associated with outcome. discussion: our study outlines weaknesses in the chain of care of dwp. emphasis should be put on respiratory rate monitoring and better assessment of severity. rationale: access to critical care is controversial in older patients for reasons: lack of available icu-beds and speculation on induced costs. in contrast, admission of young patients aged or under is infrequently questioned even though they develop catastrophic multiple-organ failure requiring full care. in addition, emotive reaction triggered in staff by these patients often represents a heavy psychological burden when icu-stay is < h. information on the epidemiology, clinical information and induced costs regarding such patients is lacking. patients and methods: this study retrospectively assessed the records of patients aged or under, and admitted from january to august . cost-related expenses charged to care-payers were obtained from our medical information department. data (number, percentages or medians) were reported and discussed by comparison with those of nonagenarians during the same period. results: of , icu-admissions, were aged or under ( %), of whom ( . %) died within the icu, with ( %) dying within h of admission despite full intensive care. the latter represent our study population ( . % of the screened population). the median age was . years , male gender was prevalent ( %). half the patients (n = , %) were referred from the emergency department, ( . %) from hematology, from oncology ( . %), from medical intermediate care units ( . %), and one from digestive surgery ( . %). the first diagnosis at admission was septic shock (n = , . %), followed by post-anoxic encephalopathy (n = , . %), coma (n = , . %), acute respiratory failure (n = , . %) and cardiogenic shock (n = , . %). sapsii was . all patients were ventilated and infused norepinephrine. two patients underwent ecmo, and others mars. mean (± sem) retribution per stay was , ± €, and mean retribution per "day of stay" €. discussion: full care of these icu-patients, with early mortality has a financial impact similar to that of nonagenarians at , ± , €; the cost per "day of stay" is therefore on average % higher than that of nonagerians (mean length of stay: . days), and, in our experience, % higher than that of average patients. conclusion: icu-patients aged or under represent a small percentage of admissions and display half our overall mortality: one third of them die within h of admission with a not insignificant financial impact for cost-payers. septic shock is the first cause of referral, followed by unexpected cardiac arrest. compliance with ethics regulations: yes. rationale: severity scores in patients with sepsis are useful for triaging and predicting mortality. mortality in emergency department sepsis (meds) score is validated in patients with sepsis in the emergency department. curb- is validated in patients with communityacquired pneumonia but not in sepsis. curb- is a simple bedside tool that has many common elements with new sepsis identification score-q sofa. the study aimed to assess the accuracy of curb- score in predicting icu admittance and mortality compared to meds score. patients and methods: this prospective study was conducted at the ed during a -month period. we enrolled all adult patients with sepsis admitted to the ed. meds and the curb- scores were calculated at admission. patients were studied using curb- score and their icu admission and in-hospital mortality were ascertained. results: a total of patients were enrolled. the mean age was ± years. % of the patients were men. % of patients had a curb- score ≥ points with a mean meds score of %. among these patients, % were admitted to icu and % died. the curb- score,was efficient in predicting both icu admittance and in-hospital mortality with an auroc of . ( % ci . - . ) and . ( % ci . - . ), respectively. conclusion: a higher curb- score was correlated with higher rates of icu admittance and mortality in patients with sepsis due to any cause. compliance with ethics regulations: yes. abderrahim achouri, hadil mhadhbi, khedija zaouche, hamida maghraoui, radhia boubaker, kamel majed university hospital center rabta of tunis, tunis, tunisia correspondence: abderrahim achouri (achouryabderrahim@gmail. com) ann. intensive care , (suppl ):p- rationale: sepsis is a major cause of mortality. in other hand, preexistent chronic diseases seem to worsen outcomes among critically ill patients. the acknowledgement of this fact may motivate studies in this type of situations in order to improve survival in sepsis. on that purpose, our study tried to check the impact of chronic pre-existent illnesses on outcomes in this type of emergency patients. patients and methods: we have included patients in whom the sepsis- definition was met throughout emergency department admission cases for infection. in this study, considered outcomes were in-hospital mortality, shock occurence and the use of mechanical ventilation. results: we collected patients admitted to ed for sepsis. mean age was years ± with bornes of and . men were % of the patients. cormorbidities were: insulin dependent diabetes mellitus in . % of patients, non insulin dependent diabetes mellitus in . %, chronic obstructive lung disease in . %, chronic renal failure in . % with % in chronic replacement therapy from total patients, coronary artery disease in . %, with stent in . % and . % with aortic coronary graft from total patients, arterial hypertension in %, chronic heart failure in . %, atrial fibrillation in . %,. death occurs in . % of total patients, septic shock in % and the use of mechanical ventilation in . %. we did not find any association between comorbidity and the use of mechanical ventilation, but association with in-hospital mortality was found in pre-existent coronary artery disease (p = . ) and in patients with coronary artery stent (p = . ). odds ratio (or) was respectively . ( % ic = [ . - . ]) and . ( % ic = [ . - . ] ). we found significant association between chronic heart failure and shock (p = . ) with or = . ( % ic = [ . - . ] ). discussion: the small size of our sample may enlimit the contibution of other comorbidities on outcomes in sepsis such chronic renal failure, especially with renal replacement therapy and diabetes mellitus. whereas, we can conclude that cardiac diseases have the most important impact on outcomes in sepsis. outcomes in sepsis can be affected by comorbidities, especially cardiac diseases. therefore, that needs large studies to check it. compliance with ethics regulations: yes. micafungin population pk analysis in critically ill patients receiving continuous veno-venous hemofiltration or continuous veno-venous hemodiafiltration nicolas garbez , litaty mbatchi , steven c. wallis , laurent muller , jeffrey lipman , jason a. roberts , jean-yves lefrant , claire roger chu nîmes, nîmes, france; university of queensland, brisbane, australia correspondence: nicolas garbez (nicolas.garbez@umontpellier.fr) ann. intensive care , (suppl ):p- rationale: to compare the population pharmacokinetics (pk) of micafungin in critically ill patients receiving continuous veno-venous hemofiltration (cvvh, ml/kg/h) to those receiving equidoses of hemodiafiltration (cvvhdf, ml/kg/h + ml/kg/h). critically ill patients in septic shock undergoing continuous renal replacement therapy (crrt) and receiving mg micafungin once daily were eligible for inclusion. total micafungin plasma concentrations were analyzed using pmetrics ® . probability of target attainment (pta) was calculated from monte carlo simulations using -hour area under curve/minimum inhibitory concentration (auc - /mic) cut-offs (c. parapsilosis), (all candida species) and (c. non parapsilosis). daily dosing regimens of , and mg were simulated for the first days of treatment. results: eight patients were included in the study. micafungin concentrations were best described by a two-compartmental pk model. no covariate, including crrt modality (cvvh and cvvhdf), was retained in the final model, confirmed by internal validation. the mean parameter estimates (standarddeviation) were . ( . ) l/h for clearance, . ( . ) l for the volume of the central compartment, . ( . ) /h and . ( . ) /h for rate constants. the standard mg daily dosing was unable to reach % of pta for all candida species except c. albicans on the second day of therapy (fig. ) . conclusion: there was no difference in micafungin pk between equidoses of cvvh and cvvhdf. a dose escalation to mg is suggested to achieve the pk/pd target of candida species with mics exceeding . mg/l in this population. these "off-label" dosing regimens should be further investigated in clinical trials knowing the favourable toxicity profile and the post-antifungal effect of micafungin in order to ensure efficacy and to prevent the emergence of resistance due to an inadequate initial antifungal dosing regimen. compliance with ethics regulations: yes. rationale: sepsis is an important cause of morbidity and mortality in hospitalized patients. recognizing and responding to patients who experience clinical deterioration remains challenging in daily practice. our purpose was to assess the ability of the quick sequential organ failure assessment (qsofa) score to identify, among patients reviewed by an intensivist, those at risk of adverse outcomes. patients and methods: retrospective cohort of patients with suspected infection reviewed by an intensivist in a university-affiliated hospital between january and june . outcomes of interest were hospital mortality and a combined criterion of hospital mortality or icu stay of days or more. results: during the study period, patients were reviewed by an intensivist, of whom ( . %) had suspected infection according to the sepsis- criteria. at the time of review, ( . %) patients with suspected infection were qsofa positive (≥ ) and ( . %) were qsofa negative ( - ). following the review, ( . %) patients were admitted to the icu, among whom ( . %) had a prolonged stay (≥ days). in-hospital mortality was . %, and . % of the patients met the combined criterion of in-hospital mortality or prolonged icu stay. qsofa positive patients required more frequently mechanical ventilation ( . % vs. . %, p = . ) and vasopressor support ( . % vs. . %, p < . ) than qsofa negative patients. moreover, qsofa positive patients had higher hospital mortality than qsofa negative patients ( . % vs. . %, p = . ). for the prediction of in-hospital mortality, a positive qsofa had a predictive positive value (ppv) of %, and a negative predictive value (npv) of %. for the prediction of in-hospital mortality or prolonged icu stay, a positive qsofa had a ppv of % and a npv of %. conclusion: hospitalized patients with suspected infection for whom a review by an intensivist was requested, are at high risk of hospital mortality. although the accuracy of qsofa for identifying patients at risk of adverse outcomes is limited, its integration in a multimodal risk assessment approach may help distinguish the subset of patients who will benefit from an escalation of care. compliance with ethicsregulations: yes. rationale: according to the sepsis- consensus, sepsis is identified as an increase of at least points in the sepsis-related organ failure assessment (sofa) score in patients who presented infection. the quick sofa or qsofa is considered as a predictive tool of sepsis and mortality when it is equal to points or more. systemic inflammatory response syndrome (sirs) criteria are of limited utility because of their low sensitivity. hyperlactatemia, as known is a determinant of tissue hypoperfusion. our objective was to evaluate the prognostic value of sofa > , sirs > , qsofa > and lactate level > mmol/l in infected patients. nine-month prospective cohort study. patients aged years or older who had a proven or suspected infection were included. sofa score, sris criteria, sofa q and lactate levels were determined within the first h of infection. the primary endpoint was hospital mortality at days. the predictive power of the studied parameters was determined using using the area under the receiver operating characteristic curve (auroc). results: a cohort of cases was studied with mean age at . years. bacterial pneumonia was the most common infection site ( %). in the first h of onset of infection the medians [iqr - ] of the sofa, sris, and sofa scores and lactate levels were respectively [ ] [ ] [ ] [ ] [ ] [ ] [ ] , [ ] [ ] , [ - ] and . [ . - . ] . the progression to severe septic status was observed in patients ( %) and norepinephrine was introduced in cases. median length of stay was days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and mortality was %. overall, the accuracy in predicting mortality of the studied parameters was poor. an increase of sofa score by at least points had greater accuracy with auroc = . [ . - . ], sensitivity = % and specificity = %. conclusion: in infected patients, the sofa score had greater prognostic accuracy than the sirs criteria, the qsofa score or the lactate level. these results suggest that sirs, qsofa, and high lactate level may be useful in screening for sepsis, but this utility is limited in predicting mortality. compliance with ethics regulations: yes. rationale: quick sequential organ failure assessement (qsofa) has been validated for patients with presumed sepsis and others in general emergency department (ed) population. however, it has not been validated in specific subgroups of patients with a high mortality. the aim of this study is to evaluate the ability of qscore to predict prognosis in patients with decompensated liver cirrhosis. patients and methods: this is a retrospective study, conducted over a period of years from january to december . consecutive patients with decompensated cirrhosis, admitted in our department are included. data of all patients were collected and the qsofa score was calculated at admission. the main study endpoints were length of stay, complications and in-hospital mortality. results: a total of patients diagnosed with decompensated cirrhosis were enrolled. mean of age was years ( - ). sex ratio was . . hcv ( %) was the main etiology of cirrhosis. the reasons of hospitalization were: oedema with ascitic syndrome in % of cases, digestive haemorrhage ( % of cases), fevers ( % of cases), and hepatic encephalopathy was present in % of cases. the mean duration of stay was days ± . in-hospital mortality rate was % and mean score qsofa was . .the qsofa score was significantly correlated with length of stay (p = . ) and complications(p = . ) but not with in-hospital mortality (p = . ). conclusion: the qsofa score was not useful for predicting in hospital mortality in patients with decompensated liver cirrhosis but it was significantly correlated to the length of stay and complications. compliance with ethics regulations: yes. angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study clara vigneron , aldéric lécluse , thomas ronzière , sonia alamowitch , olivier fain , nicolas javaud médecine interne, centre de référence associé sur les angioedèmes à kinines (créak), hôpital saint-antoine, aphp, paris, france; neurologie, chu angers, angers, france; neurologie, chu pontchaillou, rennes, france; neurologie, hôpital saint-antoine, aphp, paris, france; urgences, centre de référence associé sur les angioedèmes à kinines (créak), hôpital louis mourier, aphp, colombes, france correspondence: clara vigneron (claravigneron@hotmail.fr) ann. intensive care , (suppl ):p- rationale: bradykinin-mediated angioedema is a complication associated with thrombolysis for acute ischemic stroke. risk factors are unknow and management is discussed. the aim of this study was to clarify risk factors associated with bradykinin-mediated angioedema after thrombolysis for acute ischemic stroke. patients and methods: in a case-control study conducted at a french reference center for bradykinin angioedema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angioedema, were compared to controls treated with thrombolysis treatment without angioedema. two matched control subjects were analyzed for each case. results: thrombolysis-related angioedema were matched to control subjects. the sites of attacks following thrombolysis for ischemic stroke mainly included tongue ( / , %) and lips ( / , %). the upper airways were involved in ( %) cases. three patients required mechanical ventilation. patients with bradykinin-mediated angioedema were more frequently women ( ( %) vs. ( %); p = . ), had higher frequency of prior ischemic stroke ( ( %) vs ( %); p = . ), hypertension ( ( %) vs. ( %); p = . ), were more frequently treated with angiotensinconverting enzyme inhibitor ( ( %) vs. ( %); p < . ) and were more frequently hospitalized in intensive care unit ( ( %) vs. ( %); p = . ). in multivariate analysis, factors associated with thrombolysisrelated angioedema were female sex (odds ratio [or], . ; % confident interval [ci], . - . ; p = . ) and treatment with angiotensin-converting enzyme inhibitors ([or], . ; % [ci], . - . ; p < . ). discussion: because of theretrospective case-control design and the lack of the total number of thrombolysis for ischemic stroke, the incidence of this complication could not be evaluated in our study. previous studies reported an incidence of . to . % of angioedema in patients treated with a thrombolytic therapy for acute ischemic stroke. our case-control study permits for the first time to analyse more cases to evaluate associated risk factors of this rare complication. conclusion: this case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykininangioedema associated with thrombolysis for ischemic stroke. compliance with ethics regulations: yes. rationale: patients with inflammatory bowel disease (ibd), frequently treated by immunosuppressive drugs, are more susceptible to be admitted to the intensive care unit (icu). however, outcome and predictive factors of mortality are little known. therefore, we aimed to assess the outcome and prognostic factors for critically ill ibd patients. patients and methods: we retrospectively studied data of consecutive ibd (i.e. crohn's disease and ulcerative colitis) patients admitted in icus between and . in-icu and one-year mortalities were estimated and predictive factors of in-icu mortality were identified by univariate and multivariate analysis. results: seventy-six patients (male: %, median age: . [ . - . ] years, charlson index: [ . - . ]) entered the study. ibd type was largely represented by crohn's disease ( . %) and its localization was mostly extensive: l ( . % of crohn's disease) or e ( % of ulcerative colitis) according to the montreal classification. twenty-seven patients ( . %) were treated with corticosteroids and ( %) with immunosuppressive therapy (azathioprine: . % and anti-tnfα: %). reasons for admission were shock/sepsis ( . %) and acute respiratory failure ( . %). icu diagnoses were infection ( %), ibd flare-up ( . %) or both ( . %), and pulmonary embolism ( . %). at admission, sofa score was [ . - . ] and . fifty-three patients ( . %) required mechanical ventilation, ( . %) vasoactive drugs, and ( . %) renal replacement therapy. twenty-three patients underwent emergency surgery ( . %) and six urgent endoscopic treatment ( . %). in-icu and one-year mortality rate were . % and . %, respectively. prognostic factors of in-icu mortality were sofa score (hr . , % ci [ . - . ], p < . ) and azathioprine treatment before icu admission (hr . , % ci [ . - . ], p < . ) (fig. ) . previous immunosuppressive treatment with anti-tnf did not alter the prognosis and even the type of ibd. conclusion: our study showed that more than % of ibd critically ill patients were discharged alive from the icu and a majority of them survived after one-year ( . %). we also found that sofa score and previous azathioprine immunosuppressive treatment worsened icu outcome. higher severity of the acute event affected short-term prognosis and should be taken into account for best icu triage and management. intensivists should pay particular attention to patients treated by azathioprine. compliance with ethics regulations: yes. fig. outcome of ibd patients admitted to the icu according to precious treatment with azathioprine status all aps patients with any new thrombotic manifestation(s) admitted to icus. results: one hundred and thirty-four patients (male/female ratio: . ; mean age at admission: . ± . years), who experienced caps episodes, required icu admission. the numbers of definite, probable or no-caps episodes (fig. ) , respectively, were: ( . %), ( . %) and ( . %). no histopathological proof of microvascular thrombosis was the most frequent reason for not being classified as definite caps. overall, / ( . %) episodes were fatal, with comparable rates for definite/probable caps and no caps ( % vs. . % respectively, p = . ). the kaplan-meier curve of estimated probability of survival showed no between-group survival difference (log-rank test p = . ). discussion: our results suggest that the caps criteria do not sufficiently encompass all the parameters responsible for thrombotic aps patients' disease severity in the icu. the absence of items referring to organ dysfunction/failure in the caps criteria probably limited their ability to predict mortality. albeit useful for the retrospective classification and comparison of patients, the caps criteria may be too stringent and not yet ready-to-use for the management of icu patients. for physicians outside expert aps centres, the absence of caps criteria could be misleading and lead to rejection of the diagnosis for near-caps patients, thereby preventing them from receiving the appropriate aggressive treatment they indeed require. we think that, when confronted with a critically-ill thrombotic aps patient, caps criteria should be interpreted with caution and should not be the only elements taken into account to decide the intensity of the therapeutic management. rationale: % of resuscitation patients develop anemia during their stay, it can worsen the prognosis, prolong the length of stay and lead to transfusions that can be the cause of complications. the objective of our work is to specify the incidence of anemia in our unit, its etiologies and its therapeutic management. patients and methods: we conducted a descriptive and analytical retrospective study within the surgical emergency resuscitation department of ibn rochd university hospital of casablanca, over a period of years from to . we included all anemic patients. statistical analysis was performed with spss statistics . p < . was considered significant. results: we included patients with an estimated incidence of %, the average age was years, the sex ratio h / f was . . % of admissions were for traumatic pathology and % postoperative digestive surgery. % had hypotension at admission and the mean temperature was . % .the onset of anemia and its depth were related to length of stay with . % of patients who were anemic beyond the th day of hospitalization with a hemoglobin level that became < . g / dl beyond the th day. % of the patients had a normochromic normocytic anemia becoming microcytic with the lengthening of the duration of stay. ferritinemia dosed in % of patients and was normal. % of our patients had exclusive parenteral nutrition while % had an enteral / parenteral combination. % were transfused in red blood cells (rbc) and % of patients were transfused more than once. % received between and rbc units. in patients who received transfusion episodes costing euros, the transfusion was inappropriate. the total cost of the transfusion was estimated at around , euros. % were supplemented with oral iron with an increase in hemoglobin in % of them. % of the patients came out of the intensive care unit with a hemoglobin level < g/dl/l. the mortality rate of our patients was % with as predictive factors in multivariate analysis, hyperthermia, coagulopathy, the transfusion appears as a factor of good prognosis. the prevention of blood spoliation and the fight against inflammation and nosocomial infection remain the pillars of the management of anemia in intensive care but in view of our results and the protective role of transfusion it would be interesting to see again the transfusion thresholds in our context. compliance with ethics regulations: yes. (fig. ). discussion: we described a series of patients with severe acute viral myopericarditises associated with anti-rnapol autoantibodies, an association that has never been reported previously. the fortuitous association of these autoantibodies with acute myopericarditis is highly unlikely. acute myocarditis is a very rare disease with a reported incidence of / , inhabitants. anti-rnapol -antibody detection is also very rare: . % positive tests (including the patients in this series) out of samples during a -year period in our immunology laboratory. this % proportion of patients with proven influenza-virus infections suggest that such severe infections could trigger anti-rnapol autoantibody production. however, influenza is a common disease and anti-rnapol autoantibodies are very rare. furthermore, no anti-rnapol autoantibodies were detected in the patients with severe influenza-related ards. last, anti-rnapol autoantibodies remained detectable several months after the viral infection had been cured. conclusion: this previously unknown association between severe acute viral myopericarditis and anti-rnapol autoantibodies is probably not fortuitous. anti-rnapol antibody detection in acute myopericarditis patients could imply individual susceptibility to severe viral infection. further studies are needed to investigate the pathophysiological mechanisms involved in this entity and potential specific therapeutic strategies. fig. relative frequencies of digestive manifestations in critically ill tma patients rationale: arrhythmia-induced cardiomyopathy has been recognized for several decades, but most severe forms, i.e. cardiogenic shock and refractory cardiogenic shock requiring mechanical circulatory support, were rarely described in adults. in this retrospective study, we described patients admitted in our tertiary care center for non-ischemic acute cardiac dysfunction (or worsening of previously known cardiac dysfunction) and recent onset supraventricular arrhythmia who developed cardiogenic shock requiring veno-arterial ecmo (va-ecmo). results: in a years period, patients had va-ecmo for acute non ischemic cardiac dysfunction and recent onset supraventricular arrhythmia (table ). fourteen ( %) patients had known nonischemic cardiomyopathy and ( %) known paroxystic atrial fibrillation. cardiogenic shock was the first manifestation of the disease in patients. atrial fibrillation was the main cause of arrythmia ( % of cases). at ecmo implantation, sofa score was [ - ], inotropic score , lvef % [ - ] and lactate level was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] mmol/l. twelve patients had sustained successful reduction after amiodarone and/or electric shock, all were weaned from ecmo and survived without transplantation nor long term assist device. among the patients with failure of reduction, underwent an atrio-ventricular ablation while on ecmo and had atrial tachycardia ablation; all were weaned from ecmo and survived. among the remaining patients without reduction and without ablation procedure, only the patients who were bridged to heart transplantation or left ventricular assist device survived. in univariate analysis, factors associated with unfavorable outcome were previously known heart disease, heart rate, renal replacement therapy, nt-probnp level, failure of rhythm reduction after amiodarone load and/or electric shock. among the patients who recovered and survived ( with successful reduction and with successful ablation), lvef increased from [ - ]% before ecmo implantation to [ - ]% at long term follow-up. discussion: this is the largest cohort of arrhythmia induced cardiomyopathies on va-ecmo and the first description of atrio-ventricular node ablation with favorable outcome in this setting. conclusion: arrhythmia induced cardiomyopathy is probably underrecognized and should be considered in any patient with nonischemic acute cardiac dysfunction and recent onset supraventricular arrhythmia. recovery is possible in the most severely ill patients on va-ecmo, even with severe left ventricular dilation. aggressive rate control by av-node ablation may be warranted in case of failure of reduction, and may allow recovery and favorable outcome. compliance with ethics regulations: yes. rationale: diagnosis of sepsis is a major challenge in intensive care units and is associated with a high morbidity and mortality. sepsis identification is even more difficult in patients with extracorporeal membrane oxygenation (ecmo) because of many confounding factors. the primary objective was to study the ability of c-reactive protein (crp) and procalcitonin (pct) values measured at ecmo support initiation (day ) to predict the occurrence of early sepsis in patients undergoing venoarterial ecmo (va-ecmo) or venovenous ecmo (vv-ecmo). the secondary objectives were to study the association between these biomarkers and mortality rate during ecmo support and in-hospital mortality rate. furthermore, we investigated the relationship between early sepsis and mortality. patients and methods: we performed a retrospective, monocentric study in the cardiovascular intensive care unit of the university hospitals of lille, france. between november , and december , , we included patients over years old, who underwent an ecmo support for a medical or surgical indication, and for whom biomarkers (crp and pct) levels were available for at least the first days of admission. biomarkers and blood cultures were daily assessed for the first ecmo support days. early sepsis was defined by sepsis diagnosis in the first days after circulatory assistance initiation. in-hospital mortality rate was censored at days. after univariate analysis, a cox multivariate regression model was used to assess if the association between biomarkers levels and early sepsis or mortality rate was independent. a kaplan-meier survival plot was used to describe the association between early sepsis and mortality. results: among patients included, underwent va-ecmo and underwent vv-ecmo. an early sepsis diagnosis was made in . % of va-ecmo patients and in % of vv-ecmo patients. pct and crp levels on day were significantly associated with early sepsis diagnosis (fig. rationale: fluids are one of the most prescribed drug in intensive care, particularly among patient with circulatory failure. yet, very little is known about their pharmacodynamic properties and this topic has been left largely unexplored. several factors may impact the haemodynamic efficacy of fluids among which the infusion rate. the aim of this study was to investigate the influence of the rate of fluid administration on the fluid pharmacodynamics, in particular by studying mean systemic pressure (pms). we conducted a prospective observational study in patients with septic shock to compare two volume expansion strategies. a fluid bolus, ml of normal saline were administered and several haemodynamic variables were recorded continuously: cardiac output (co), arterial pressure (ap), mean systemic pressure (pms, estimated from ci, pvc and map). infusion rate was left at the discretion of the attending physician. a "slow" and a "fast" groups were determined based on the median of the infusion duration. fluids effect was measured by the area under the curve (auc), maximal effect (emax) and time to maximal effect (tmax) for each haemodynamic variable. the effects of fluid on psm disappeared in one hour on average. compared to patients of the "slow" group, those of the "fast" group had a shorter tmax and a higher emax for pms (p = . and . respectively). the auc for pms was identical between group, while in case of similar effect of infusion rates, it should be larger in the "slow" group. regarding co, tmax was also shorter in the "fast" than in the "slow" group (p = . ). the decreasing slope from maximal effect was comparable between groups, for pms as for co. the effect of a ml fluid bolus with normal saline in septic shock patients vanished within one hour. a faster infusion rate increased the maximal and total effect of the fluid bolus and shortened the delay to reach the maximal effect. rationale: significant hypotension following spinal anesthesia is a common issue in everyday clinical practice. toavoid this potentially harming situation, an empirical fluid administration is usually performed before the procedure. inferior vena cava (ivc) ultrasound has been demonstrated effective in guiding fluid therapy in critical care patients. the purpose of this study was to evaluate the ivc ultrasound guided volemic status optimization in order to decrease post-spinal hypotension rate. patients and methods: in this prospective, controlled, randomised study, consecutive patients were recruited and patients were randomly assigned to a control group, consisting of pre-anesthesia empirical fluid administration (itt), an ivc ultrasound group in which fluid management was based on an ivc ultrasound evaluation, and a passive leg raising test (plrt) group in which volume optimization was performed following the above mentioned test. primary outcome was the hypotension rate reduction after spinal anaesthesia following fluid optimization therapy between the groups. secondary outcomes were the total fluid amount administered, the total vasoactive drug amount used and the time needed to realize the whole anaesthetic procedure in all three groups. results: % reduction in hypotension rate ( % ci - %, p = . ) was observed between the echocardiography group and the control group, and there was a reduction of hypotension rate by % (ci % - %, p = . ) between the echocardiography group and the plrt group. the total fluid amount administered was significantly greater in the ultrasound group than in the control group ( ml; sd ml, versus ml; sd ml, p = . ). the total amine consumption was % in control group, % in ivc group and % in plrt group. an increased of total study time was observed for the echocardiography group min (sd min) in comparison with the control group min (sd min) and ptlr group min (sd min), (p < . ). the study showed a faint but positive trend toward the use of ivc-ultrasound to identify patients in spontaneous breathing needing fluid optimization before spinal anesthesia compliance with ethics regulations: yes. rationale: we performed a systematic review and a meta-analysis of studies investigating the ability of the end-expiratory occlusion (eexpo) test to predict preload responsiveness, through the changes in cardiac output (co) or its surrogates, in adult patients. this meta-analysis was prospectively registered on prospero (crd- ). we screened pubmed, embase and cochrane database to identify all original articles published between and evaluating the ability of the eexpo test to predict a significant increase in co or surrogate, compared to the one induced by a subsequent volume expansion or by passive leg raising (plr). the meta-analysis determined the pooled area under the receiver operating characteristics curve (auroc) of eexpo testinduced changes in co to detect preload responsiveness, as well as pooled sensitivity and specificity and the best diagnostic threshold. subgroup analysis and sensitivity analysis were planned to investigate potential sources of heterogeneity. results: thirteen studies ( patients) were identified and included in the analysis. nine studies were performed in the intensive care unit and four in the operating room. preload responsiveness was defined according to co changes induced by fluid administration in studies (fluid-induced increase in co ≥ % or ≥ %) and according to co changes induced by plr in one study. the duration of the respiratory hold ranged between and s. for the eexpo test-induced changes in co, the pooled sensitivity and specificity were [ - ]% and [ - ]%, respectively, while the pooled auroc curve was . ± . (fig. ) . the corresponding best diagnostic threshold was . ± . %. when changes in co were monitored through pulse contour analysis compared to other methods the accuracy of the test was significantly higher ( ( ). continuing (decrease to % of peak level) or modification (decrease < %) of antibiotic therapy was guided by a serum pct assay from the third day of treatmentand every h until antibiotic was stopped. this last was stopped when pct levels had decreased of % from the initial value. results: a total of patients had been diagnosed as sepsis (n = , %) and septic shoc (n = , %). mean age was years ± . an average ubs and absi score of % and . the average length of stay in icu was days. patients were assigned into two groups: group a (favorable evolution, n = ); group b (unfavorable evolution, n = ). the therapeutic attitude according to the kinetics of the pct are presented in the table . we found a significant difference between patients with unfavorable evolution compared to those with a favorable evolution (in whom we stopped antibiotics) (p < . ), in terms of hemodynamic state, pct concentration and renal clearance. pctguided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in our patients. the average duration of antibiotic was . ± days. conclusion: pct measurement may help with the decision to initiate antibiotic therapy in low risk acuity of infection and allows more judicious antibiotic use by reducing antibiotic exposure. compliance with ethics regulations: not applicable. rationale: reducing the risk of severe hypoxemia during endotracheal-intubation (eti) is a major concern in intensive care unit but little attention was paid to co variations during this period. we conducted a prospective observational study to describe transcutaneous co (ptcco ) throughout intubation in patients who received preoxygenation with standardoxygen therapy (sot), non-invasive ventilation (niv), or high flow nasal cannula oxygen therapy (hfncot). patients and methods: patients over years undergoing eti in icu were continuously monitored for ptcco during intubation and the following h under mechanical ventilation (mv). haemodynamics and respiratory parameters were also recorded as well as arterial partial pressure of co (paco ) to evaluate reliability of the transcutaneous measure. results: two hundred and two patients were included in the study. we found a strong correlation between ptcco recorded at preoxygenation and the last paco available before intubation (r = . , p < . ). in % of patients ptcco values recorded at initiation of mv were out of - mmhg ranges. ptcco recorded at eti, at initiation of mv, min and h of mv were significantly higher than ptcco during preoxygenation (p < . by anova). variations of ptcco were significantly different according to the preoxygenation method (p < . for interaction in anova). lastly, a decrease in ptcco higher than mmhg within half an hour after the beginning of mv was independently associated with postintubation hypotension (pih) (odds ratio = . , % confident interval . - . , p = . ). conclusion: ptcco is a valuable tool to record paco variation in patients requiring invasive mechanical ventilation and could be useful to prevent pih. compliance with ethics regulations: yes. rationale: intubation in intensive care unit (icu) is a critical procedure which leads to serious adverse event in to % of cases. several recent trials were conducted to help physicians to choose medications, devices and modality of intubation. especially, videolaryngoscope (vl) led to several publications in the last few years, with increasing tools marketed and spread use (difficult airway management, routineintubation). we designed an online survey to take a picture of intubation process and devices availability in france. toolbox. it was positioned as a first line laryngoscope for every intubation in critically ill patients to reinforce the vl skill training. present study was performed using prospectively collected data from a continuous quality improvement database about airway management in a -beds french teaching hospital medical icu. all consecutive intubation procedure performed with vl from september to june were included. "first attempt success" group and "first attempt failure" group were compared by univariate and multivariate analysis in order to analyze the first attempt intubation success rate according to the level of operators' expertise, identify factors associated with first pass intubation failure and describe the intubation related complications. results: we enrolled consecutive endotracheal intubations. overall first attempt success rate was ( %). comorbidities, junior operator, the presence of cardiac arrest and coma were associated with a lower first attempt success rate. the first attempt success rate was less than % in novice operators ( - previous experiences with vl, independently of airway expertise with direct laryngoscopies) and % in expert operators (greater than previous experiences with vl) (fig. rationale: tracheostomy in intensive care unit (icu) has many advantages. but only patient comfort and shorter icu and hospital stay were demonstrated. the timing of this procedure is still debated. the aim of this study was to determine the impact of early tracheostomy on prognosis. we performed a retrospective study in a medical icu ( beds unit) from january to november . the technique of tracheostomy was exclusively surgical in the operating room made by the surgeon. the primary endpoint was mortality in icu. the secondary outcomes were post-tracheostomy incidence of ventilator acquired pneumonia, duration of mechanical ventilation and length of stay in icu. these criteria were assessed in relation to timing of the tracheostomy defined as early when performed before day of mechanical ventilation. results: forty-two patients were enrolled during the study period. mean age of patients was ± years. median length of stay in icu was of days. mortality rate was of %. comparing the two groups, early vs late tracheostomy, no difference was found with respect to mortality ( % vs. %, p = . ), vap occurrence ( % vs. %, p = . ), post-tracheostomy duration of mechanical ventilation ( ± d vs. ± d, p = . ), or length of stay in icu ( ± d vs. ± d, p = . ). in multivariate analysis, the only factor independently related to mortality was the sofa score patient on tracheostomy day with p = . and or = . (ci % [ . - . ] ). conclusion: tracheostomy in the intensive care unit remains a justified alternative despite the discordant data in the literature. in our study, the delay of the procedure didn't interfere with the evolution. however, the patient severity as attested by sofa score at the day of tracheostomy, was the only independent prognostic factor. those results should be confirmed by other large prospective studies. compliance with ethics regulations: not applicable. sabah benhamza, mohamed lazraq, youssef miloudi, abdelhak bensaid, najib el harrar réanimation de l'hôpital du août, casablanca, morocco correspondence: sabah benhamza (benhamzasabah @gmail.com) ann. intensive care , (suppl ):p- rationale: many unknowns remain as to the place of tracheostomy in intensive care. reluctance to perform a tracheotomy is numerous, especially when pre-exists chronic respiratory failure, but some data suggest benefits. we report in this work our experience in tracheotomy in the intensive care unit of the august hospital, casablanca. patients and methods: this is a retrospective descreptive study over years (january to january ) including all patients that have been tracheostomized in the intensive care unit of the august hospital . results: during the study period, patients were tracheostomized with a prevalence of . % in years, the predominance was male (sex ratio . ). the average age was ± years old. the indication for tracheostomy was prolonged ventilation in % of cases, extubation failure in % of cases, and intubation failure in % of cases. tracheostomy was performed on average on the th day of intubation. all patients were tracheostomized in the operating room by ent surgeons. the main complications attributable to tracheotomy were hemorrhage of the tracheostomy orifice in patients ( %) immediately resumed, cases of subcutaneous emphysema ( %), case of pneumothorax ( %), cases of orifice infection ( %). no patient died of a tracheostomy related cause. the tracheotomy in intensive care is still a subject of debate especially concerning the time of its realization. however it seems to reduce the duration of mechanical ventilation, facilitates the care and also the ventilatory weaning. compliance with ethics regulations: yes. rationale: hfnco is a frequently used device providing heated and humidified high flow oxygen with several advantages: decreased work of breathing, decreased dead space, increased end expiratory lung volume (eelv), more stable fio . the increase in eelv is relying of the positive expiratory effect generated by the device. the level of generated pep seems however to largely depend on whether the mouth is open or not. this study was aimed to assess the impact of mouth opening on eelv increase induced by hfnco using electric impedance tomography. patients and methods: the following hfnco trial was proposed to healthy subjects who used hfnco on a regular basis for patients care. oxygen flow was set successively during min periods at , and l/min (optiflowtm; fisher & paykel healthcare, auckland, nz). these three conditions were tested in semi recumbent and supine position chosen at random. measurement started in supine position with no flow (baseline) and each period was separated from the following by a wash out period on min during which the subject could breath normally with no supplemental oxygen. electric impedance tomography (pulmovista ® , dräger medical gmbh, lündbeck, germany) was performed applying a electrodes belt placed between the th and th intercostal space, including a reference electrode located on the abdomen. as no spirometer was used, the data of eelv computed on the eit device were expressed as percentage of variation of the value measured in supine or semi recumbent position with no flow. demographic data were expressed as median and extreme values. comparisons were performed using u mann whitney test. [ . - . ] accepted to participate to the study. when subjects received hfnco with open mouth (whatever position) no modification of eelv was observed (table ) . conversely, a significant increase in eelv was noted with closed mouth, whatever position. in the semi recumbent position the increase in eelv was even more important with l/min. conclusion: electrical impedance tomography illustrates the impact of mouth closure on eelv increase among healthy subjects receiving hfnco. compliance with ethics regulations: yes. rationale: in stable copd patients, nasal high flow oxygen (nhf) use can be associated with reduction in respiratory rate (rr) and minute ventilation (mv). in thesepatients, paco remains stable or decreases under nhf. this suggests a possible dead space reduction related to a washout effect of nhf. the aim of this study was to assess the physiological effects of nhf in hypercapnic patients with acute copd exacerbation. patients and methods: crossover study in hypercapnic patients suffering from acute copd exacerbation and treated with intermittent non-invasive ventilation (niv). nhf l/min or standard oxygenotherapy (stand o ) were randomly administered during h between niv treatments. rr, tidal volumes (vt), mv and corrected mv (cormv = mv x paco / ) variations were recorded during the last min of each study period using a respiratory inductive plethysmography vest. blood gas analysis was performed at the end of each oxygen administration period. visual analogic dyspnea score (vas) quoted from to was assessed by the patient after and min. results given as median [iqr] . wilcoxon tests were used to compare data between stand o and nhf. results: twelve patients were included and data could be recorded in ( (fig. ). dyspnea scores were not different between the modalities. conclusion: in case of acute copd exacerbation, using nhf between niv treatments was associated with paco and rr decrease. mv concomitantly decreased suggesting a deadspace volume reduction related to a washout effect of nhf. corrected mv decreased in all the patients except one. these results suggest that nhf could be used to deliver oxygen between niv treatments to copd patients suffering from acute exacerbation and could contribute reducing paco . compliance with ethics regulations: yes. rationale: the role of atypical micro-organisms in acute exacerbation of chronic obstructive pulmonary disease (copd) that require mechanical ventilation is poorly none. the aim of this study was to determine the role of atypical pathogens in severe acute exacerbation of copd. patients and methods: in this prospective study we included all patients admitted for acute exacerbation of copd requiring mechanical ventilation. atypical pathogens (chlamydophila pneumoniae and mycoplasma pneumoniae) were searched by serological diagnosis and by culture of sputum samples. in this study we included patients aged ± years. sixty-eight percent of sputum culture were considered significant. six cultures were positive with different microorganisms. neither chlamydophila pneumoniae nor mycoplasma pneumoniae were found. the prevalence of chlamydophila pneumoniae was . % (positive igg serum). the demographic characteristics was similar between patients with and without positive culture. the rate of noninvasive ventilation (niv) failure was % in positive serology group versus % in negative serology group (p = . ). the mortality was similar in both groups. in multivariate logistic regression analysis only positive serology (or = . ; % ic [ . - . ], p = . ) was an independent factor of niv failure. conclusion: a positive serology of chlamydophila pneumoniae was a predictive factor of niv failure without an impact on the morbidity and mortality of copd patient treated with mechanical ventilation. compliance with ethics regulations: yes. rationale: emergency departments (ed) receive a growing up number of patients with acute exacerbation of chronic obstructive pulmonary disease (copd) .non-invasive ventilation (niv) could be a good alternative to achieve a respiratory support, avoiding as much as possible the complications of invasive ventilation. the study aimed to assess the clinical outcomes of using niv in acute exacerbation of copd at ed and to identify whether clinical variables present at admission are predictive of niv failure. we conducted a prospective study conducted at the ed over a period of one year. data of all patients admitted for acute exacerbation of copd for all causes and requiring non-invasive ventilation were collected. niv failure was defined as need for endotracheal intubation or death. results: during the study period, a total of patients with a mean age of years (± ) were included. acute exacerbation of copd was due to bronchitis in %, to pneumonia in % of cases. % of patients had no apparent etiology of acute exacerbation of copd. bilevel positive airway pressure was performed on all patients, during a mean period of h (± ). clinical niv success was observed in patients ( %). the predictors of niv failure were advanced age, tachycardia, and hypercapnia. conclusion: the efficiency of niv in the management of acute exacerbations of copd at ed is well documented. this is further supported by our study which showed a clinical success in % of patients with acute exacerbation of copd. compliance with ethics regulations: yes. rationale: non invasive ventilation (niv) is often performed in elderly patients with acute respiratory failure (arf) at emergency department (ed). this technique may be subject to many difficulties, due to the presence of frequent co-morbidities. the aim of this study was to identify the predictive factors of niv failure in elderly patients with arf at ed. patients and methods: this was a retrospective study conducted at ed on year and months including patients aged more than years and who required the use of niv for an arf. all data were collected and analyzed using the spss software. patients were divided into two groups: niv failure and niv success. niv failure was defined by inhospital mortality, requirement of intubation or hospitalization at intensive care unit. results: during the study period, a total of elderly patients that required niv for arf were included. median age was years (min = , max = ) and sex ratio was . . the median charlson index was (min = , max = ). the etiological diagnoses of arf were acute decompensation of chronic obstructive pulmonary disease ( %), acute heart failure ( %), pneumonia ( %) and pulmonary embolism ( %). the arf was hypercapnic in % of cases and nonhypercapnic in %. niv failure concerned %. predictive factors of niv failure were clinical signs of right heart dysfunction (p < . ), c reactive protein (p = . ), initial ph (p = . ) and kidney dysfunction (p < . ). conclusion: in our study, niv failure in elderly patients with arf at ed was influenced by clinical signs of right heart dysfunction, c reactive protein, initial ph and kidney dysfunction. these clinical and biological factors could be useful to identify the most critical elderly patients and to better guide therapeutic decisions. compliance with ethics regulations: yes. rationale: the interest of ecco r in the management of very severe acute asthma exacerbations is still unclear. since it could help to control respiratory acidosis and /or to limit dynamic hyperinflation, its clinical benefits are uncertain, even in mechanically ventilated patients. the rexecor observatory is a prospective ecco r cohort in the great paris area. tencases of severe asthma treated by ecco r were retrospectively reviewed. mainly, arterial blood gases (abg), duration of ecco r and imv were collected and in-icu mortality were assessed. data are reported as median (iqr). results: ten patients ( men, age: (ic: - ) years, bmi: . (ic: . - . ) kg/m , fev- : . (ic: . - . ) l, ( (ic: - ) %), saps : . (ic: . - . ) points) were included. one patient suffered from cardiac arrest before admission and one had pneumothorax at icu admission. nine patients were under imv (started on the day of admission for ). before ecco r, patients received systemic corticosteroids, paralyzing agents, epinephrine and salbutamol. two patients suffered from pneumonia. ecco r was started (ic: - . ) days after intubation. venous vascular access was achieved via the right internal jugular route in patients and via the femoral route in . the hemolung device was used in patients, the ila activve in and the prismalung in . abg before and after day of ecco r are reported in table . duration of ecco r was (ic: . - ) days and patients were weaned from imv under ecco r. for the remaining patients, duration of imv after ecco r was (ic: - . ) days. icu stay was . (ic: - . ) days. the only one niv patient was not intubated. ecco r as stopped in patients because of complications (one hemolysis, one internal bleeding and one membrane clotting). one patient died in icu after limitation of life-sustaining therapy decision. we report a preferential use of ecco r in imv patients, contrasting with a marginal use in only one niv patient to prevent intubation. the mortality rate was low, in line with previous case series of severe acute asthma with ecmo or ecco r support. more studies are needed ( ) to better delineate the pathophysiological benefits of ecco r in asthma patients and ( ) to confirm strong clinical benefits. compliance with ethics regulations: not applicable. rationale: acute exacerbations of chronic obstructive pulmonary disease (aecopd) are the most important events characterizing respiratory illness progression. their management often needs noninvasive or invasive ventilation (iv). data of literature confirm that the mortality of aecopd requiring iv is high but are discordant about prognostic factors. the aim of our study was to describe the epidemiologic and clinical features of patients admitted for aecopd requiring iv, the treatment and the evolution in intensive care unit in order to deduce the independent factors of mortality. patients and methods: a -year retrospective analytic observational single-center study including patients hospitalized for aecopd requiring iv. results: fifty-eight patients were enrolled. mean age was ± years with sex-ratio of . . eighty one percent were smokers and % were classified gold stage . history of intensive care hospitalization and prior iv were found in % and % of all cases respectively. mean apache ii score was ± . the predominant precipitating factor for aecopd was respiratory tract infection ( % of all cases). twenty two percent of all patients presented septic shock. iv was initiated on admission in % of all cases and after noninvasive ventilation failure in % of all cases. forty-eight per cent of all patients developed septic shock as evolutionary complication. mortality rate was %. in univariate analysis: male gender (p = . ), duration of respiratory disease progression (p = . ), annual exacerbations frequency (p < − ), gold stage (p = . ), prior iv (p < − ), duration of symptoms before hospitalization (p = . ), apache ii score (p = . ), ph (p = . ), shock on admission (p = . ) and septic shock as evolutionary complication (p = . ) were predictors of mortality in our study. besides; shock on admission (p = . ) and as evolutionary complication (p = . ) were the two independent prognostic factors in multivariate analysis. conclusion: vital and functional prognosis of aecopd requiring iv depends on the severity of the underlying respiratory illness, the severity of the exacerbation and the quality of an early management. this emphasizes the importance of controlling modifiable risk factors including smoking cessation, basic treatment improvement and early appropriate treatment of these exacerbations. compliance with ethics regulations: yes. medical background, biological parameters, death-rate and outcome of patients have been compared. results: in total, patients have been included in the "hlh" population. death-rate in intensive care unit was % in the "hlh" group compared to % in the "not hlh" group (p = . ). we used more extrarenal cleansing in the "hlh" group ( % vs. %, p < . ), the duration of assisted ventilation was longer ( . days vs. . days, p < . ), as well as the duration of extrarenal cleansing ( . days vs. . days, p < . ) and those of amines ( . days vs. . days, p = . ). the average time of hospitalization was significantly longer in the "hlh" group ( . days vs. . days, p < . ). the secondary hlh to sepsis in intensive care unit, not well known and understudied, seems to have a different profile and a more serious outcome but no change in death-ratehas been found considering the pairing with the sofa. further studies are needed to plan a better therapeutic strategy within this population. compliance with ethics regulations: not applicable. serum and peritoneal exudate concentrations after high doses of ß-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study lisa leon, philippe guerci, elise pape, nathalie thilly, amandine luc, adeline germain, anne-lise butin-druoton, marie-reine losser, julien birckener, julien scala bertola, emmanuel novy chru nancy, vandoeuvre les nancy, france correspondence: lisa leon (lisaleon @gmail.com) ann. intensive care , (suppl ):p- rationale: critically ill patients with severe intra-abdominal infections (iais) requiring urgent surgery may undergo several pharmacokinetic alterations that can lead to ß-lactam under dosage. the aim of this study is to measure serum and peritoneal exudate concentrations of ß-lactams after high doses and optimal administration schemes. patients and methods: this observational prospective study included critically ill patients with suspicion of iai who required surgery and a ß-lactam antibiotic as empirical therapy. serum and peritoneal exudate concentrations were measured during surgery and after a h steady-state period. the pharmacokinetic/pharmacodynamic (pk/ pd) target was to obtain ß-lactam concentrations of % ƒt> x mic (minimum inhibitory concentration) based on a worst-case scenario (highest ecoff value) before bacterial documentation (a priori) and redefined on the mic of the isolated bacteria (a posteriori). results: forty-eight patients were included with a median [iqr] age of [ - ] and a saps ii score of . septic shock occurred in % of cases. the main diagnosis was secondary nosocomial peritonitis. piperacillin/tazobactam was the most administered ß-lactam antibiotic ( %). prior to bacterial documentation, patients ( . %) achieved the a priori pk/pd target. iai was documented in patients ( %). enterobacteriaceae were the most isolated bacteria. based on the mic (n = ) of isolated bacteria, % of the patients achieved the pk/pd target ( % ƒt> xmic). in the fig. we presented serum ß-lactams pk/pd target attainment and observed total concentrations of piperacillin-tazobactam at each timepoint in serum and peritoneal exudate. in critically ill patients with severe iais, high doses of ß-lactams ensured % ƒt> xmic in % of critically ill patients with severe iais within the first h. a personalized ß-lactam therapeutic scheme with a pk/pd target based on local ecology should be warranted. compliance with ethics regulations: yes. rationale: intensive care unit acquired bloodstream infections (icu-bsi) are frequent, and associated with high morbidity and mortality rates. the objective of our study was to describe the epidemiology and the prognosis of icu-bsi in our icu (cayenne general hospital). secondary objectives were to search for factors associated to icu-bsi caused by esbl-pe, and those associated with mortality at days. patients and methods: we retrospectively studied icu-bsi in the medical-surgical intensive care unit of the cayenne general hospital, during months (january to june ). we assessed survival at days from the diagnosis of icu-bsi. results: icu-bsi was diagnosed in . % of admissions giving a density incidence of . icu-bsi/ days. the median delay to the first rationale: necrotizing soft tissue infections (nsti) are a heterogenous group of severe infections. among them, group a streptococcal (gas) infection represent a subgroup that could benefit from specific therapies targeting the toxinic pathway, such as intravenous immunoglobulins or clindamycin. nevertheless, previous trials evaluating these treatments suffered from a low rate of gas infection among the study population. early identification of patients at high risk of gas infection would allow for assessing targeted treatment strategies. patients and methods: we conducted a secondary analysis of a previously published cohort of patients admitted to our tertiary center for surgically proven nsti between and . admission characteristics and microbiological documentation based on surgical samples, blood cultures or subcutaneous puncture were recorded. we compared patients with a documented gas infection to all other patients regarding admission characteristics. a generalized linear regression model was used to identify admission characteristics associated with a subsequent documentation of gas infection. results: among patients, ( %) had a gas infection, which was monomicrobial in ( %) cases. admission characteristics associated with gas infections by univariate analysis were nsaid treatment before admission ( ( . %) for gas infections vs ( . %) for others, p = . ) and leukocytosis as a continuous variable ( , /mm [ , - , ] vs. , [ - , ], p = . ). those inversely correlated with gas infections were immunodeficiency ( ( %) vs. ( . %), p = . ), and an abdominoperineal topography ( ( . %) vs. ( . %), p > . ). after multivariate analysis only immunodeficiency (or = . [ . - . ], p = . ) and an abdominoperineal infection (or = . [ . - . ], p = . ) remained associated with the absence of gas infection. using these criteria allowed for identifying subgroups of patients with increased likelihood of gas infections: from % overall (n = ) to % for non-abdominoperineal infections (n = ), % for patients without immunodeficiency (n = ) and % for both non abdominoperineal infections in patients without immunodeficiency (n = ). a sensitivity analysis for monomicrobial gas infections yielded similar results with the addition of younger age and non-nosocomial infections as predictors. conclusion: upon admission, the absence of immunodeficiency and of an abdominoperineal infection in nsti patients were covariables associated with gas infection. compliance with ethics regulations: yes. rationale: sickle-cell disease is the most common genetic disorder in the world. a complication of this disease is the acute chest syndrome (acs) which is associated with a high risk of death. respiratory tract infections are often mixed up and the introduction of betalactam antibiotics is recommended. glomerular hyperfiltration is common and responsible of a high risk of underdosing. this study compares cefotaxim continuous infusion to intermittent bolus in adult patients with acs. patients and methods: this observational retrospective monocentric study included acs admitted in intensive care unit and treated by cefotaxim with at least one plasmatic dosing between may and august . results: thirty patients received bolus administration while the others received continuous infusion. we observed patients ( %) and patients ( %) with a cefotaxim trough level ≥ mg/l in the bolus and continuous group, respectively (p < . ). the median residual concentration was mg/l [ - ] and . mg/l [ . - . ] in the bolus and continuous group, respectively (p < . ). there was no toxic effect induced by overdosing of cefotaxim. conclusion: compared to intermittent bolus infusion, continuous cefotaxim administration maximizes the pharmacokinetics parameters by obtaining a plasmatic concentration times above the minimal inhibitory concentration of usual germs associated with acs. continuous infusion of time-dependant antibiotics seems to decrease the risk of underdosing in patients with sickle cell disease. compliance with ethics regulations: not applicable. (n = , %), followed by esophageal varices rupture (n = , %), ulcer bleeding (n = , %) and diverticular hemorrhage (n = , %). infectious diseases were diagnosed in three patients ( %), including one clostridium colitis, one erosive gastritis with helicobacter pylori and one esophageal candidiasis. conclusion: gib is associated with a high mortality rate in immunocompromised patients, especially in patients with hematological malignancies. specific malignant lesions were the main etiology and may be difficult to treat. comparison with critically ill non-immunocompromised patients with gib will help physicians to provide specific therapeutic strategies in this population. compliance with ethics regulations: yes. risk factors for delayed defecation and impact on outcome in critically ill patients: a multicenter prospective non-interventional study benoît painvin ,* , arnaud gacouin , antoine roquilly , claire dahyot-fizelier , sigsimond lasocki , chloe rousseau , denis frasca , philippe seguin anesthésie-réanimation/chu rennes, rennes, france; réanimation médicale/chu rennes, rennes, france; réanimation chirurgicale/ chu nantes, nantes, france; réanimation chirurgicale/chu poitiers, poitiers, france; anesthésie-réanimation/chu angers, angers, france; centre investigation clinique/chu rennes, rennes, france; anesthésie-réanimation/chu poitiers, poitiers, france; réanimation chirurgicale/chu rennes, rennes, france correspondence: benoît painvin (painvinbe@gmail.com) ann. intensive care , (suppl ):p- rationale: delayed defecation is very common in intensive care units (icu) and it increases length of mechanical ventilation (mv), icu length of stay (los) and possibly mortality. the objective of this prospective multicenter study was to determine risks factors for constipation in icu and to evaluate their impact on mortality. patients and methods: it was a prospective multicenter non-interventional trial performed in university icus in france from january to october . all patients ≥ years old who had an expected los of days and mechanically ventilated for at least days were eligible. defecation was defined as the time of the first stool passage. results: patients were included in the analysis. a stool passage was observed in % of the patients during their icu stay with a mean delay of ± days. in multivariate analysis, risk factors for delayed passage of stool were non-invasive ventilation use and time spent under invasive ventilation whereas alcoholism, laxative treatment (before and after icu admission) and nutrition ≤ h favoured passage of stool (table ) . no relations between constipation and mortality were found. conclusion: we highlighted new and important independent factors for constipation in critically ill patients leading to a better prevention of this phenomenon.. compliance with ethics regulations: yes. rationale: community peritonitis is a frequent medical-surgical emergency of the adult, acquired by the patient in a non-hospital setting. careful multidisciplinary care is essential, involving surgeons, anesthetists, microbiologists and radiologists. the objective of our study is to determine the bacteriological aspects of intra-abdominal sepsis, to describe their sensitivity profiles and to propose treatment regimens for the management of community peritonitis. we conducted a descriptive retrospective study spanning a period of two years from january to january involving cases of community abdominal sepsis operated in the operating room of surgical emergencies of our hospital. we included in our study adult patients admitted for suspected or confirmed abdominal sepsis who had undergone bacteriological examinations on the abdominal collections. samples taken are sent directly to the bacteriology laboratory for bacteriological analysis of the results. the studies showed the mean age is . years old, with a sex ratio of . . we found positive results mainly of peritoneal origin with a percentage of . % peritonitis, dominate by intestinal peritonitis . % followed by the appendicular origin . % then peritonitis by perforation of ulcer. the most incriminated organism in intraabdominal sepsis is e. coli with a percentage of . % of the total germs found, followed by streptococcus spp . %, enterococci . %, non-fermenting bgn composed mainly of pseudomonas aeruginosa . %, staphylococci . % and acinetobacter baumanii . %. note also the presence of bacteroides fragilis is %. e. coli had a very low sensitivity profile for amoxicillin/clavulanic acid ( . %), unlike ceftriaxone, gentamicin, amikacin and ertapenem, which had a sensitivity of . %, respectively. . %, %, . %. conclusion: knowledge of the bacterial ecology of intraabdominal sepsis is important in the choice of probabilistic antibiotherapy, pending bacteriological findings. no data are yet available about nutritional management and risk of malnutrition in tunisian medical intensive care units (icu). the purpose of this study was to describe nutritional management in medical intensive care patients and to evaluate the risk of malnutrition. patients and methods: we conducted a prospective observational cross-sectional study in medical icus all around the tunisian country on the th september . all participant units received a questionary form about routine nutritional management and data of all patients hospitalized in icu on the study day. collected data were: demographic characteristics, reason for admission, severity scores and subjective evaluation of nutritional status on admission, type and volume of nutritional support on the study day and the day before, nutritional status, nutric score and biological data on the study day, reasons for nutritional interruption and other supports prescribed. results: thirteen icu all around tunisia participated to the study. no icu had a nutrition team and only one had a written nutrition protocol. four icus evaluated systematically the nutritional status on admission. all icus were aware and practiced early enteral nutrition in patients unable to maintain oral intake with a systematic supplementation of oligoelements and minerals. neither target energy nor protein intake were calculated. on the study day, patients were hospitalized with an occupation rate of %. mean age was ± years. mean body mass index was ± and % of patients were judged well nourished. enteral nutrition support was prescribed on admission in % of cases with a mean caloric intake of ± kcal/day. the mean caloric target on the study day was ± kcal/day with a mean caloric intake of ± kcal/day and a mean caloric gap of ± kcal/day. the mean nutric score and body mass index on the study day were ± and ± respectively. twenty patients were judged malnourished by the nutric score and twenty two by clinical evaluation. a good correlation was found between nutric score and clinical evaluation of nutritional status (k = . ). conclusion: tunisian icus don't have nutrition team or nutritional written protocol. early enteral feeding and supplementation is common. a good correlation exists between nutric score and clinical nutrition status evaluation. compliance with ethics regulations: yes. rationale: whether more intensive glycemic control (gc) is beneficial or harmful forcritically ill patient has been debated over the last decades. gc has been shown hard to achieve safely and effectively in intensive care. the associated increased hypoglycemia and glycemic variability is associated with worsened outcomes. however, modelbased risk-based dosing approach have recently shown potential benefits, improving significantly gc safety and performances. the stochastic targeted (star) gc framework is a model-based controller using a unique risk-based dosing approach. star identifies modelbased patient-specific insulin sensitivity and assesses its potential variability over the next hours. these predictions are used to assess hypoglycemic risks associated with a specific insulin and/or nutrition intervention to reach a specific target band. this study analyzes preliminary clinical trial results of star in a belgian icu compared to the local standard protocol (sp). the mean age in our series was . years with a male predominance (sex ratio = . ). the main revealing symptoms were epigastralgia, weight loss and vomiting. subtotal gastrectomy was performed in . % of cases and total gastrectomy in . % of cases. curative resection could only be performed in . % of cases. operative mortality was . % and morbidity was . %. the main factor influencing operative mortality was age greater than years. in univariate analysis the main prognostic factors; tumor size, degree of parietal invasion, presence of ganglionic invasion, presence of more than ganglia invaded, presence of metastases, locally advanced tumor, tumor stage and curative nature of resection. patient-related factors such as age associated blemishes and biological factors have a significant influence on the patient's prognosis. the prognosis of gastrectomies, although it has improved overall, remains mediocre. the only way to improve the prognosis remains the early diagnosis with an effective surgical management and the introduction of an adapted resuscitation. compliance with ethics regulations: yes. efficacy of multiple second line agents in refractory status epilepticus in a pediatric intensive care unit lea savary, claire le reun chu tours, tours, france correspondence: lea savary (lea.savary@hotmail.com) ann. intensive care , (suppl ):p- rationale: convulsive status epilepticus (cse) is the most common neurological emergency in children. refractory status epilepticus (rse) occurs whenseizures are not controlled with first-and secondline agents. in adults, rse requires pharmacological induced coma. in pediatric patients, association of second line treatment is often used to avoid general anesthesia although there is currently no data on the efficacy of this association. we performed a monocentric retrospective study to assess the efficacy of multiple second line agents in pediatric rse. all children admitted to clocheville hospital (tours) between january and december with a diagnosis of rse were included. our population was divided into two groups: need of general anesthesia (midazolam+) or not (midazolam-). results: children were included ( in group midazolam+, in group midazolam−) during the study period. among the patients with multiple second line agents, % did not need general anesthesia (n = ). in group midazolam+, cse was % longer in patients treated with multiple second line agents ( rationale: drowning is an acute respiratory failure resulting from immersion or submersion in a liquid. patients and methods: we report cases of drowning collated in the pediatric reanimation department during a period from to . the aim of our retrospective study was to analyze and compare the different epidemiological, clinical, parcalinical, therapeutic and evolutionary of drowning in our study. results: our study contains boys and girls, with a sex ratio (m/f) of , in an age between months and years. for cases studied, no one was classified stage i, . % classified stage ii, % stage iii, and . % stage iv. all cases collected by ou service were victim of accidental drowning, . % were secondary to the lack of parental supervision. among cases, had respiratory complications, cases of hydroelectrolytic disorders, case with infectious complications, cases of neurological and cases of cardiac or hypothermic complication. in our study, cases recovered well and cases died. the survival of the drowned person depends on the speed and efficiency of the intervention, which in thefirst place is prehospital, thus ensuring the first actions at the scene of the accident, which will have repercussions on the hospital care. this has an equal share in the improvement of the victim's prognosis. compliance with ethics regulations: not applicable. epidemiology of severe pediatric trauma following winter sport accidents in the northern french alps emilien maisonneuve , nadia roumeliotis , pierre bouzat , guillaume mortamet chu grenoble, grenoble, france; chu sainte-justine, montréal, canada correspondence: emilien maisonneuve (emilienmaisonneuve@orange. fr) ann. intensive care , (suppl ):p- rationale: this study describes the epidemiology of severe injuries related to winter sports (skiing, snowboarding and sledding) in children, and assesses potential preventive actions. we did a single-center retrospective study in our pediatric intensive care unit in the french alps. we include all patients less than years old, admitted to the intensive care unit following a skiing, snowboarding or sledding accident from to . results: we included patients (mean age . years and % were male); of which ( %), ( %) and ( %) had skiing, snowboarding and sledding accidents, respectively. the average iss (injury severity score) was . the major lesions were head (n = patients, %) and intra-abdominal (n = patients, %) injuries. compared to skiing and snowboarding, sledding accidents affected younger children ( vs. years, p < . ); most of whom did not wear a helmet ( % vs. %, p < . ). severity scores were similar amongst winter sports (iss = for skiing, for snowboarding and for sledding accident, p = . ). rationale: best strategies for the management of severe pediatric traumatic brain injury (tbi) are still not clearly established and wide variations among professional practices have been reported in the literature. unfortunately, these variations in practice have an impact on the patient's outcome. the objectives of this work were to assess the adequacy of professional practices to the guidelines for the management of severe head injury and to assess the level of agreement of respondents in the absence of guideline. patients and methods: a practice survey was conducted in frenchspeaking hospitals in canada, belgium, switzerland and france from april st to june th, . the survey was conducted as a progressive clinical case with questions based on guidelines and the literature from to . the questions related to the assessment and management of tbi during the acute and intensive care phase. results: seventy-eight questionnaires were included. the adherence to guidelines was good, with items out of obtaining an adherence rate of more than % regardless of the annual number of tbi managed by the centre. there was strong agreement among clinicians on the intracranial pressure (pic) (> %) and cerebral perfusion pressure (> %) thresholds used according to age. guidelines for indication of pic monitoring were almost perfectly followed in the case of glasgow score < and abnormal brain ct scan (n = , %). on the other hand, the natremia and glycemia thresholds and the role of transcranial doppler were not consistent. strong adherence to recent recommendations was achieved: seizure prophylaxis with levitracetam (n = / , %) and capnia threshold (n = , %). assessment of o pressure in brain tissue (n = , %) and autoregulation (n = ; %) was not a common practice. conclusion: overall, practices for the management of tbi appear to be standardised. variations persist in areas where there is a lack of literature and guidelines in paediatrics, so clinicians seem to refer to adult guidelines. compliance with ethics regulations: yes. choubeila guetteche chu constantine, constantine, algeria correspondence: choubeila guetteche (cguetteche@gmail.com) ann. intensive care , (suppl ):p- rationale: ingesting a coin cell is a common household accident in children, which can have serious consequences. the goal is to determine prognostic factors to improve management and reduce complications. patients and methods: we conducted a retrospective study including children under admitted in pediatric intensive care between january and may for ingestion of button cells, with epidemiological, clinical and paraclinical data collection. results: twenty-six children boys ( %), and girls ( %) were included, with an average age of months ( - ), increased incidence in recent years. clinical signs indicative were dysphasia with hyper-sialorrhea in cases, cervical pain in one case, respiratory distress in one case, the cell was located in the upper third of the esophagus in cases, third average in cases, third inferior in cases, the mean time before extraction was h. complications: cases of mediastinitis, cases of oesotracheal fistula, a case of perforation. conclusion: the young age of the child, the diameter of the battery, and especially the time of care are risk factors for the occurrence of complications, the prevention passes through the education of the general public and creation of channel of taking into account fast charge. compliance with ethics regulations: not applicable. yacine benhocine university hospital center nedir mohamed, tizi-ouzou, algeria correspondence: yacine benhocine (yacine @yahoo.fr) ann. intensive care , (suppl ):p- rationale: inhalation of foreign bodies is a common and serious accident in children, especially between and years old. at this age, children use their mouth to explore their environment. asphyxia is the immediate risk and respiratory sequelae may appear secondarily. the severity of this incident has been considerably reduced due to the progress of the instrumentation and anesthesia which condition the smooth running of the therapeutic act. aim: to evaluate the anesthetic modalities of the extraction of the foreign bodies of the airways in children, in order to optimize our care with a maximum of security. a prospective, mono-centric, descriptive study from january to november of patients treated for inhalation of foreign bodies in the airways. study population wasdefined by: age, sex, hospitalization context, physical and radiological examination data, anestheticmanagement. results: the average age of the patients was . months, the male predominated ( %), and the hospitalization context was polymorphic. general anesthesia was necessary in all cases, sevoflurane mainly for narcosis; the combination of an opioid in . % of cases and a curare in . %. spontaneous ventilation is desirable, but % was manually broken down intermittently between extraction attempts. cases of desaturation, bronchospasm, bradycardia, and pneumothorax have been reported. . % had a good evolution. discussion: the results of the epidemiological data are consistent with those of the literature. the penetration syndrome is very revealing. the chest x-ray is the key examination, the diagnosis is often based on indirect signs. in case of asphyxia by foreign body enclosed above or between the vocal cords, laryngoscopy and oxygenation is the first step to perform. in other cases, a rigid bronchoscopy is performed under general anesthesia; inhalation induction with sevoflurane is the technique of choice for many experienced authors. controlled ventilation is used in the majority of cases because spontaneous ventilation is not often not possible. the heterogeneity of anesthetic practices accounts for the multiplicity of clinical situations. conclusion: the inhalation of a foreign body is a diagnostic and therapeutic emergency. extraction of the foreign body takes place under general anesthesia, which is difficult and at risk. compliance with ethics regulations: yes. non-invasive neurally adjusted ventilatory assist (nava) in infants with bronchiolitis: a retrospective cohort study alex lepage-farrell, sally al omar, atsushi kawaguchi, sandrine essouri, philippe jouvet, guillaume emeriaud chu sainte justine, université de montréal, montréal, canada correspondence: alex lepage-farrell (alex.lepage-farrell@umontreal.ca) ann. intensive care , (suppl ):p- rationale: bronchiolitis is one main reason for admission to pediatric intensive care unit. most infants are successfully managed with nasal cpap or high-flow nasal cannula, but about a third of these patients are not sufficiently supported and require an alternative support. non-invasive neurally adjusted ventilatory assist (niv-nava) improves patient-ventilator interactions and could therefore improve the effectiveness of non-invasive support. our hypothesis is that niv-nava is feasible in infants with bronchiolitis and that it reduces the respiratory effort. patients and methods: we retrospectively studied all patients under years of age with a clinical diagnosis of bronchiolitis ventilated with niv-nava in our pediatric intensive care unit, between october and june . patients characteristics, respiratory and physiologic parameters, including diaphragmatic electrical activity (edi) were extracted from an electronic medical database (data collected every s). respiratory effort was estimated using the modified wood clinical score for asthma (mwcas) and the inspiratory peak edi, and -h periods before and after niv-nava initiation were compared (wilcoxon rank test). the study was approved by the local research ethics committee. results: during the study period, patients were admitted with bronchiolitis; infants ( boys) with a median ( th- th percentile) age of ( - ) days were treated with niv-nava after a failure of other non-invasive support methods, and all were included. twentyfive subjects ( %) had at least one comorbidity. the interfaces used were predominantly face masks ( %). the maximum ventilatory settings were nava level of . ( . - . ), peep of ( - ) cmh o, fio of % ( - ) and maximal pressure of ( - ) cmh o. total duration of non-invasive ventilation was ( - ) hours, including ( - ) hours in niv-nava. as detailed in the table , mwcas significantly decreased after niv-nava initiation, from . ( . - . ) to . ( . - . ), p < . . a decrease in inspiratory peak edi was also observed, which was particularly clinically relevant in infants with high baseline edi (> mcv). capillary blood ph and pco also significantly improved after niv-nava introduction. six patients ( %) needed escalation to endotracheal intubation. conclusion: this study confirms the feasibility of niv-nava in infants with bronchiolitis after failure of first line non-invasive support, with a low failure rate. niv-nava initiation was followed by a decrease in respiratory effort and an improvement in blood gases. this observational study supports the needs for prospective interventional trial. compliance with ethics regulations: yes. rationale: the use of blood transfusion is frequent in pediatric intensive care units and has increased significantly since . considered as therapeutic, it requires an assessment of the benefit / risk balance before making the transfusion decision. the aim of our study is to describe the transfusion practices in the pediatric resuscitation department of the ehs canastel, algeria. patients and methods: a retrospective observational study over a -month period from january of any blood transfusion performed in hospitalized patients, in the pediatric intensive care unit. we studied : the age, the sex, the history of blood transfusion, the indication of transfusion, the haemodynamic and respiratory parameters, the transfusional accidents, the length of stay in intensive care, the evolution after a blood transfusion. results: these included transfusion patients out of hospitalizations during the -month period, mean age was months.all patients had no transfusion history, % of patients had their anemia admission and % developed it during their stay. the reason for hospitalization was respiratory distress in %, convulsive condition in %, polytrauma in %, and head trauma in %. the indication of the transfusion was placed on a hb inferior or equal to g / dl in % of cases, in % on an hb superior to g / dl in addition to the clinical criteria of intolerance to anemia; in % of the cases no clinical or biological criteria found, the nature of the blood products was of the red cell in % of the cases and of the plasma concentrate in / of the cases and pfc in %. % received a+, % of a-, % of b+, % of o+ and % of o-. % of the patients had a transfusion-like reaction at min after the start of the transfusion; % of the patients were under artificial ventilation and % were under hemodynamic support, % under diuretic.the average length of stay was days; the favorable outcome was % of the patients after the transfusion with an increase in the hb level beginning, % of the patients had complications of their pathology and the death in % of the cases. conclusion: current transfusion practices in children often do not reflect the implementation of our current knowledge of the need for transfusion. hence the need to review the protocols and practice other transfusion alternatives to avoid complications and improve the quality of care. compliance with ethics regulations: not applicable. rationale: bacterial multi drug resistance is medical actuality nowadays, because of its morbidity and mortality especially in intensive care, it constitutes a real problem in our hospitals. we conducted a retrospective descriptive study, to identify bacterial drug resistance profile of patients with cross infections in the department of intensive care in august hospital. this study included patients hospitalized between st january and st december . the data was collected from medical records of this unit as from the register of the bacteriology service of ibn rochd university hospital. results: patients were hospitalized in the resuscitation service, of which had nosocomial infection, an incidence of . %. the mean age of the patients was years with male predominance (sex ratio . ), the average stay in intensive care was days. the site of infection was pulmonary in % of cases, blood in % of cases, urinary in % of cases, central catheter in %, neuro-meningeal in . % of cases. the germs isolated were: acinetobacter baumanii in . % of cases, pseudomonas aeroginosa in . % of cases, klebsiella pneumonia in . % of cases, enterococcus feacalis in . % of cases, e.coli in . % of cases and staphylococcus aureus in % of cases. acinteobacter baumanii showed resistance rates of up to % for the impenem and % for amikacin. regarding pseudomonas, it was resistant to impenem in % of cases and in % of cases to amikacin. compared to klebsiella, resistance to imipenem was % and % for amikacin. the mortality rate of infected patients was % conclusion: in the light of this work, we found that important emergence of multidrug resistance bacteria in intensive care unit is related to not only the immunocompomised state of patients but also to daily bad practices of health professionals such as the misuse of antibiotics. compliance with ethics regulations: yes. overnight culture of escherichia coli, klebsiella pneumoniae, staphylococcus aureus and pseudomonas aeruginosa, was also sequenced. results: twenty-four samples and the pc were analyzed. amplicon sequence analyses found similar results with the two primer pairs in % of cases. cultured pathogen was found in % ( / ) for human primer pair and in % ( / ) for earth primer pair. for each eta, ngs revealed bacteria unknown as pathogen globally identified as oropharyngeal flora in conventional microbiology (table ) . alpha diversity decreased for all vap patients overtime, average shannon . ( ; . ) versus ( . ; . ), and was higher in upper respiratory tract (os) versus lower respiratory tract (eta): average shannon . ( . ; . ) vs. . ( . ; . ) (ns). conclusion: this pilot study highlights the impact of s rdna amplification procedures (especially oligonucleotide sequences) used on the results in microbiome research. concordance between ngs and bacterial culture, as well as similar evolution of the alpha diversity than previously described ( ), enables us to validate our methodology using the "gut primers" pair f- r. these findings allow furthers major studies on the pulmonary microbiome of icu ventilated patients including comparison according to the occurrence of a vap or not. compliance with ethics regulations: yes. rationale: in the field of intensive care only few studies have explored bacterial microbiota whereas virome remained hardly considered. it appears essential to describe both evolution in mechanically-ventilated patients to improve the pathophysiological understanding of ventilator-associated pneumonia (vap) development. to date no study had been simultaneously conducted on lower respiratory tract with a single nucleic acid extraction before metagenomics analysis of bacterial microbiota and virome. we conducted a preliminary study to validate our methodology based on a common automated extraction of nucleic acids. patients and methods: twelve mechanically ventilated patients were selected: five who developped (vap) and seven controls (c) who did not. endotracheal aspirate (eta) were collected between intubation and day (or dvap for vap patients). conventional bacterial microbiology and multiplex respiratory viruses pcr were also performed. total nucleic acids were extracted using nuclisens easymag extractor. for the bacterial microbiota, region v of the s rrna genes was amplified. for the virome, the nextera dna xt kit (illumina) and rna seq trio kit (nugen) protocols were used to prepare viral dna and rna libraries. libraries underwent paired-end sequencing on the illumina miseq (bacteria) or nextseq- (virus) platform. after bioinformatics analysis we compared the performance of metagenomics analysis with conventional bacterial culture and other common viral detection methods. results: for culturable bacteria, concordance between conventional microbiology and sequencing was found in % ( / table . our preliminary results confirm the feasability of exploring both bacterial microbiota and virome on the same sample using a common extraction method. data from metagenomics were highly concordant with conventionnal detection methods for known pathogenic viruses and bacteria in lower tract respiratory sample and enables identification of other microorganisms. this is the first step for a large cohort study that aims to compare evolution of global lung microbiome in patients at risk of vap and assess how bacteria and virus interplay. compliance with ethics regulations: yes. references . clancy department of medical and toxicological critical care, lariboisière hospital one microorganism was isolated in . % and two in . % of cases. the main isolated microorganism were enterobacteriaceae in . % of patients. they were esbl-producers in . % of cases. initial antibiotic therapy was appropriate in . % of cases. factors independently associated with esbl-pe as the causative microorganism of icu-bsi were esbl-pe carriage prior to icu-bsi the sensitivity of esbl-pe carriage to predict esbl-pe as the causative microorganism of icu-bsi was . %, and specificity was . %. mortality at days was . % in the general population in multivariable analysis, there was no parameter which was independently associated to mortality at day from the occurrence of icu-bsi. conclusion: icu-bsi complicates . % of admission to icu and was associated with % in-hospital mortality assessing and applying individualized treatment for group a streptococcal necrotizing soft-tissue infection is possible service de réanimation médicale intensive care decompressive craniectomy in traumatic brain injury: about cases karama bouchaala sex ratio of . . the mean (sd) length of stay in icu was . ± . days. the mean glasgow coma score (gcs) (sd) was . ± . and gcs ≤ in . %. sofa score > was found in patients ( . %) and sapsii score ≥ in patients ( . %). the cerebral ctscan at admission showed acute subdural hematoma (asdh) in ( . %), cerebral oedema ( . %) and cerebral contusions ( %) teaching: fresenius medical care; patent or product inventor: gml czech republic banydeen rishika: no conflict of interest baptiste amandine: no conflict of interest baptiste olivier: no conflict of interest barbar saber davide: no disclosure barbier françois: no disclosure barbierlouise: trainings, teaching: ethicon, astellas; invitation to national or international congresses: sandoz, astellas barnerias christine: no disclosure baron aurore: no disclosure baron elodie: no conflict of interest barr att -due andreas: no disclosure barrau stephanie: no disclosure barraud damien: no disclosure barraud helene: no disclosure barrois brigitte: no conflict of interest baruchel andré: no disclosure bastide marie anaïs: no conflict of interest baudel jean-luc: no conflict of interest baudin florent: invitation to national or international congresses: dr baudin has received speaking fees from maquet critical care (epnv teaching: drager; invitation to national or international congresses: msd; hill rom beganton frankie: no conflict of interest begot erwan: no disclosure beinse guillaume: research support/scientific studies: association pour la recherche contre le cancer ion and fresenius kabi bensaid abdelhak: no disclosure bensardi fatimazahra: no disclosure benyamina mourad: no disclosure benzerara laurent: patent or product inventor: aphp benzerdjeb nazim: research support/scientific studies: amarape, icap; consultancy, expert: alphasights, msd; trainings, teaching: msd beqiri erta: no disclosure bÉranger agathe: no conflict of interest berard emilie: no conflict of interest berdai adnane: no disclosure berger patrick: no disclosure bernal william: no disclosure bernardin gilles: no disclosure berrada lina: no conflict of interest berthaud romain: no conflict of interest berthet guillaume: no conflict of interest berti enora: no conflict of interest bertoli sarah: no disclosure bertrand pierre-marie no conflict of interest besbes lamia: no disclosure besbes mohamed: no conflict of interest besch camille: invitation to national or international congresses: abbvie no conflict of interest boisseau chloé: no disclosure boissel nicolas: no disclosure boissier florence: no conflict of interest boivin alexandra: no conflict of interest bonacorsi stéphane: no conflict of interest bongiovanni filippo: no conflict of interest bonnardel eline: no conflict of interest bonnefoy-cudraz eric: no disclosure bonnet sixtine: no conflict of interest bonnevie tristan: research support/scientific studies invitation to national or international congresses: fresenius kabi and fresenius medi-calcare bucur petru: no disclosure buetti niccolo: research support/scientific studies: swiss national science foundation research grant and bangerter rhyner foundation supporting my postdoc bui hoang-nam: no disclosure burelli gabrielle: no conflict of interest burgel pierre-régis: no disclosure burghi g: no conflict of interest bustarret olivier: no conflict of interest butin-druoton anne-lise: invitation to national or international congresses expert: astra-zeneca; 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invitation to national or international congresses: msd frouin antoine: no conflict of interest frugier alexandre: no disclosure gaboriau louise: no conflict of interest gaci rostane: invitation to national or international congresses: bard gacouin arnaud: no disclosure gaddas mehdi: no conflict of interest gaillard arnaud: trainings, teaching: zoll medical gaimard sophie: no conflict of interest gainnier marc: no conflict of interest galbois arnaud: no conflict of interest galerneau louis-marie: invitation to national or international congresses: agir À domicile galicier lionel: consultancy, expert: novartis, eusapharma; trainings, teaching: baxalta, pfizer; invitation to national or international congresses no conflict of interest ichaÏ philippe: no conflict of interest imen sioud: no conflict of interest ioos vincent: no disclosure iserin franck: no disclosure issa nahema: no conflict of interest jaber samir: consultancy, expert: drager, fisher-paykel; medtronic; baxter xenios fresenius; invitation to national or international congresses: drager no conflict of interest jacq gwenaëlle: no conflict of interest jacquet emmanuelle: research support/scientific studies: unicancer (esme and storm studies invitation to national or international congresses: pfizer université laval-qc-ca labbe vincent: no disclosure labro laura: no disclosure lacaille florence: no conflict of interest lacampagne alain: no disclosure lacan claire: no conflict of interest lacherade jean-claude: no conflict of interest ladjemi maha-zohra: no conflict of interest lafon charles: no conflict of interest lafon marie-edith: no disclosure lafon thomas: no conflict of interest lagache laurie: invitation to national or international congresses advertising documents: philips; trainings, teaching: novartis, gsk, astra zeneca, boeringher; invitation to national or international congresses: chiesi, astra zeneca, sos oxygene, novartis, boeringher lamoth frédéric: consultancy, expert: gilead, msd, basilea; invitation to national or international congresses: msd expert: norgine; trainings, teaching: fujifilm, boston scientific lebreton guillaume: no disclosure lebrun-vignes benedicte: research support/ scientific studies: novartis; consultancy, expert: ansm lebuffe gilles: no disclosure leclerc maxime: no conflictof interest lÉcluse aldéric: research support/scientific studies: pgrx avc study; consultancy, expert: bms-pfizer, boerhinger ingelheim, bayer; invitation to national or international congresses: bms-pfizer, boerhinger ingelheim ledoux didier: no disclosure lefebvre francois: no conflict of interest macloughlin ronan: research support/scientific studies: aerogen ltd no conflict of interest mari arnaud: no conflict of interest marie damien: no conflict of interest marijon eloi: no disclosure mariotte eric: consultancy, expert: sanofi-aventis marjanovic nicolas: no disclosure marjanovic zora: no disclosure maroni arielle: no conflict of interest marot benoit: no conflict of interest marque sophie: no conflict of interest marti teaching: zambon, chiesi; invitation to national or international congresses no conflict of interest matusik elodie: no conflict of interest mauchien benedicte: no conflict of interest maury eric: research support/scientific studies: doran international, drager; trainings, teaching: vygon maxime virginie: no conflict of interest mayaux julien: invitation to national or international congresses stock shareholder: tanderev; patent or product inventor: tanderev mercat alain: research support/scientific studies: fisher-paykel, general electric; consultancy, expert: faron pharmaceuticals no disclosure merhabene takoua: no conflict of interest merle jean-claude: no disclosure mesotten dieter: no conflict of interest messaadi amenallah: no conflict of interest messika jonathan: invitation to national or international congresses: cslbehring; fisher&paykel metaxa victoria: no disclosure metogo mbengono junette arlette: no conflict of interest meunier anne: no conflict of interest meurice jean-claude: no disclosure meybeck agnes: consultancy, expert: janssen, gilead; invitation to national or international congresses teaching: msd no conflict of interest morimont philippe: no conflict of interest moro-sibilot denis: no disclosure mortamet guillaume: no conflict of interest mosbah nabil: no conflict of interest moschietto sebastien: no conflict of interest moucadel virginie: research support/scientific studies: biomérieux moulaire rigollet valérie: no disclosure mouliade charlotte: no conflict of interest moulin florence: no disclosure mounir yousfi: no conflict of interest mourabit karima: no disclosure mourvillier bruno: trainings, teaching: msd research support/scientific studies: aerogen; advertising documents: aerogen; patent or product inventor: aerogen musiari michele: no conflict of interest n'guyen quang-thang: no conflict of interest n'guyen tran: no disclosure nabil mosbah: no disclosure naccache lionel: no disclosure naimi skander: no conflict of interest nakaa sabrine: no disclosure nallet-amate megan: no conflict of interest natalis eloïse: no disclosure naudin jérôme: invitation to national or international congresses: novartis nay mai-anh: no conflict of interest nemlaghi safaa: no conflict of interest neofytos dionysios: research support/scientific studies: msd; consultancy, expert: msd, gilead, pfizer; invitation to national or international congresses: gilead, pfizer nesseler nicolas: no conflict of interest neviere remi: no disclosure nguyen alexandre: no disclosure nguyen khoa thao: no conflict of interest nicolau-travers marie-laure: no disclosure niÉrat marie cécile: no conflict of interest nieszkowska ania: no disclosure nigeon olivier: no conflict of interest nitel gautier: no conflict of interest nodea elena madalina: no conflict of interest noel marine: no conflict of interest nogier marie-béatrice: no disclosure noorah zaid: no disclosure nouira wiem: no conflict of interest noumeir rita: stock shareholder: softmedical noury norbert: no conflict of interest novy emmanuel: research support/scientific studies: msd; invitation to national or international congresses: pfizer expert: air liquide medical system ollivier veronique: no conflict of interest onimus thierry: no conflict of interest oppenheimer anne: invitation to national or international congresses: gedeon richter orkisz maciej: no conflict of interest orliaguet gilles: research support/scientific studies research support/scientific studies: oxynov; patent or product inventor: oxynov patrier juliette: no conflict of interest paugam catherine: no disclosure paul marine: no conflict of interest paul-bellon rachel: no disclosure paulo nicolas: no conflict of interest pavot arthur: invitation to national or international congresses: fresenius medical care france pehlivan jonathan: no conflict of interest peigne vincent: invitation to national or international congresses: air liquide pÉju edwige: no conflict of interest pene frédéric: consultancy, expert: alexion pÉpin-lehalleur adrien: invitation to national or international congresses: chiesi pere morgane: no conflict of interest pereira bruno: no disclosure perez didier: no disclosure perez pierre: no disclosure perez yonatan: no conflict of interest perier françois: no disclosure perin nicolas: no conflict of interest biomerieux robin emmanuel: no conflict of interest robin nicolas: no disclosure robineau olivier: no disclosure roch antoine: no disclosure roche anne: no conflict of interest roger claire: consultancy, expert: pfizer, fre-senius medical care; invitation to national or international congresses: msd,pfizer rolle amélie: no conflict of interest rondeau eric: no disclosure ronziÈre thomas: no disclosure roquilly antoine: no disclosure rosselli sylvène: no disclosure rouby jean-jacques: no disclosure rouis sana: no conflict of interest rouleau stéphane: no conflict of interest roulet sylvie: no disclosure roulland charlotte: no disclosure roumeliotis nadia: no conflict of interest rousse natacha: no disclosure rousseau anne-françoise: invitation to national or international congresses no disclosure sagnier anne: no disclosure saillard colombe: trainings,teaching: amgen, novartis; invitation to national or international congresses no conflict of interest schmidt aline: no disclosure schmidt matthieu: consultancy no disclosure schultz marcus: no conflict of interest schwebel carole: invitation to national or international congresses: pfizer scicluna brendon: no disclosure sculier jean-paul: no conflict of interest see perrine: no conflict of interest seghboyan jean-marie: no disclosure seguin amelie: no conflict of interest seguin philippe: consultancy, expert: lfb; invitation to national or international congresses: astellas sejourne caroline: no conflict of interest sellami walid: no conflict of interest sendid boualem: research support/scientific studies: allfun project, fp european commission; invitation to national or international congresses: pfizer senhadji lahcen: no conflict of interest serbouti rita: research support/scientific studies: fresenius medical care; consultancy, expert: fresenius medical care; trainings, teaching: fresenius medical care; invitation to national or international congresses: fresenius medical care serfaty lawrence: no disclosure sÉrie mathieu: no conflict of interest shaw geoffrey m.: no conflict of interest shi rui: no conflict of interest shimi abdelkrim: no disclosure shojaei maryam: no disclosure si-tahar mustapha: consultancy, expert: cynbiose respiratory; stock shareholder: cynbiose respiratory siami shidasp: no conflict of interest silva daniel: research support/scientific studies: fresenius medical care france; consultancy, expert: fresenius medical care france; invitation to national or international congresses: xenios novalung, heilbronn no conflict of interest sirault bruno: no disclosure sirodot michel: no disclosure slama michel: no disclosure slim amine: no disclosure smielewski peter: no disclosure soares marcio: stock shareholder: epimed solutions teaching: gilead; invitation to national or international congresses: pfizer spagnoletti marco: no conflict of interest steckelmacher claire: no disclosure stockx luc: research support/scientific studies: phenox, medtronic; consultancy no conflict of interest voiriot guillaume: research support/scientific studies: biomérieux, sos oxygène, janssen; consultancy, expert: biomérieux; invitation to national or international congresses: biomérieux von kietzell matthias: invitation to national or international congresses expert: aguettant; invitation to national or international congresses: vifor yacoubi wejden: no conflict of interest yager hélène: no conflict of interest yahya yosra: no conflict of interest yakini khalid: no disclosure yakouben karima: no disclosure yonis hodane: invitation to national or international congresses: lvl medical et pfizer younan romy: no conflict of interest youssoufa atika: no disclosure zacharia mahi: no disclosure zafrani lara: research support/scientific studies: jazz pharmaceuticals zambon olivier: no disclosure zaouak nadia: no conflict of interest zaouche khedija: no conflict of interest zarrougui wafa: no conflict of interest ze minkande jacqueline: no disclosure zeghdoud dalila: no disclosure zerbib yoann: no conflict of interest zerhouni amel: no conflict of interest zerhouni amine: no conflict of interest zerimech farid: no conflict of interest zerouali khalid: no disclosure zheng yi: no conflict of interest zimmerli stefan: research support/scientific studies: msd, pfizer, gilead; consultancy, expert: msd, pfizer; trainings, teaching: gilead; invitation to national or international congresses springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations farhat hached hospital, sousse, tunisia; yassminet regional hospital, ben arous, tunisia; habib bougatfa regional hospital, bizerte, tunisia; larabta hospital, tunis, tunisia; carthagene private hospital, tunis, tunisia; regional hospital of zaghouan, zaghouan, tunisia; regional hospital of tozeur, tozeur, tunisia; habib thameur hospital, tunis, tunisia correspondence: samia ayed (samia.ayed@yahoo.fr) ann. intensive care , (suppl ):p- geoffroy hariri, kyann hodjat-panah, laurene blum, jean-rémi lavillegrand, idriss razach, naike bige, jean-luc baudel, bertrand guidet, eric maury, hafid ait-oufella médecine intensive-réanimation, hôpital saint-antoine, paris, france correspondence: geoffroy hariri (geoffroyhariri@hotmail.com) ann. intensive care , (suppl ):p- rationale: hemolytic anemia (ha) is a common condition in intensive care unit but its diagnosis remains challenging. free hemoglobin (and heme) degradation leads to co release that can bind to hemoglobin to form carboxyhemoglobin (hbco). we hypothesized that hbco concentration could be used as a reliable diagnosis tool for ha. patients and methods: we performed a monocentric retrospective study in a -bed intensive care unit at st antoine hospital, paris, between and . all patients hospitalized for ha with arterial hbco dosage at admission were included. arterial hbco was measured in routine in our department with an il system ph/ blood gas analyzer. demographic and biological data were collected. a group control of patients with non-hemolytic anemia (hb < g/ dl) (nha) was also included. finally, we analyzed patients outcome according to hbco changes during icu stay. results: between and , patients with ha were included. nha patients were included in the control group. patients with ha were younger than patients with nha ( [ ; ] vs. [ ; ] years old, p = . ) but admission sofa was not different between groups ( [ ; ] , vs. [ ; ] , p = ns). among patients with ha, % had thrombotic microangiopathy, % had autoimmune hemolytic anemia and % had sickle cell disease. at icu admission, ha patients had higher hbco level than patients with nha ( . [ . ; . ] vs. . [ . ; . ] %; p < . ). hbco was a reliable biomarker of hemolysis (auc . ( . ; . ) p < . ). an hbco level threshold at . % identify hemolysis with a sensitivity ( - ) % and a specificity ( - ) %. in ha group, hbco was negatively correlated to hb level (r = . ; p < . ). in ha patients, changes of hbco level during icu management were associated with outcome, decreasing in survivors ( . [ ; . ] vs. . [ . ; . ] ; p = . ) but not in non-survivors ( . [ . ; . ] vs. . [ . ; . ] %; p = . ). conclusion: carboxyhemoglobin is a reliable diagnosis and prognosis biomarker for hemolytic anemia in icu compliance with ethics regulations: yes. rationale: thrombocytopenia is the most commonly hemostatic disorder encountered in intensive care, present in to % of patients. the mortality associated with this thrombocytopenia, the numerous pathological contexts associated with resuscitation and the lack of a recommended management strategy led to the establishment of these guidelines. the aim of our study was to determine the incidence, causes and risk factors associated with the occurrence of thrombocytopenia, as well as the impact of thrombocytopenia on the mortality and length of stay in the icu ibn medical resuscitation unit. rochd de casablanca, over a period of months. patients and methods: this was a prospective study, carried out in the medical resuscitation department of ibn rochd university hospital in casablanca over a period of months. there were two groups: ''sick'' group with thrombocytopenia with a platelets count < , / mm , and a ''control'' group without thrombocytopenia. patients with previous platelet disorders, hematologic malignancies, and patients undergoing chemotherapy were excluded. of the patients included, episodes of thrombocytopenia were identified, anoverall incidence of . %. sepsis was incriminated times ( . %), followed by ards in patients ( . %), massive filling in patients ( . %), disseminated intravascular coagulation in patients ( . %), and massive transfusion in patients ( . %). the drug origin was incriminated in patients ( . %). it was due to quinolones and imipenem. the mortality rate was deaths ( . %) which was inversely proportional to the lowest platelet count in the thrombocytopenia group, compared to deaths ( %) in the control group. the mean duration of stay in the thrombocytopenia group was ± days with extremes ranging from to days. conclusion: thrombocytopenia was a common abnormality in the intensive care system, it occured in many pathological situations and was a factor of morbidity and excess mortality. the most common etiology in this study was sepsis. the diagnostic and therapeutic approach depended on the particular clinical context in which thrombocytopenia occurs. its onset may constitute a hematological emergency, particularly when there is a major mucocutaneous and / or visceral hemorrhagic syndrome, which necessitates a rapid etiological diagnosis, and the establishment of an effective treatment, both symptomatic and specific. compliance with ethics regulations: not applicable. marc pineton de chambrun , romaric larcher , frédéric pene , laurent argaud , alexandre demoule , rémi coudroy , elie azoulay , yacine tandjaoui-lambiotte , stanislas faguer , alain combes , charles-edouard luyt , zahir amoura sorbonne université, aphp, hôpital la pitié-salpêtrière, institut de cardiométabolisme et nutrition (ican), service de médecine intensive-réanimation, paris, paris, france; rationale: catastrophic antiphospholipid syndrome (caps), the most severe manifestation of antiphospholipid syndrome (aps), is characterised by simultaneous thromboses in multiple organs. diagnosing caps can be challenging but its early recognition and management is crucial for a favourable outcome. this study was undertaken to evaluate the frequencies, distributions and ability to predict mortality of "definite/probable" or "no-caps" categories of thrombotic aps patients requiring admission to the intensive care unit (icu rationale: septic acute kidney injury (s-aki) is a frequent complication in critically ill patients and is associated with high morbidity and mortality. it is well known that chronic kidney disease increases the risk of pulmonary embolism (pe), but few studies have investigated the relationship between acute kidney injury (aki) and pe occurrence in septic patients. the aim of this study is to determine whether patients with aki are at increased risk of developing pe. patients and methods: were included, in a prospective study conducted over months (january -june , ) in a medical surgical intensive care unit, all the patients older than years with septic shock at admission or during hospitalization. two groups were compared: patients with kidney injury (aki+ group) and patients without kidney injury (aki− group). we studied the occurrence of pe in these two groups. results: we included patients. the mean (sd) age was . ( ± ) years. sex ratio was . . thirty one ( . %) patients developed pe. the occurrence of pe was significantly higher in (aki + group) [ patients ( %) vs. patients ( %); p = . ]. the incidence of pe according to kidney injury severity was patients ( %) kdigo i, patients ( %) kdigo ii, patients ( %) kdigo iii. in the aki+ group, pe was significantly associated with increased sofa score at admission ( points vs. points; p = . ), lower platelets count ( , vs. , ; p = . ), higher lacatatemia at septic shock day [ . vs. . mmol/l; p = . ] and higher c reactive protein level [ mg/l vs. mg/l; p = . ]. in a multivariate analysis the pe risk factors in (aki+ group) were thrombopenia (odds ratio = . ; ci [ . - . ], p = . ) and c-reactive protein value (odds ratio = . ; ci[ . - . ], p = . ). discussion: the increased risk for pe with aki may be due to endothelial involvement, vascular injury and the related changes found in procoagulant proteins (increased levels of fibrinogen, factor vii, factor viii, von willebrand factor, and plasminogen activator inhibitor- ). in our study, lower platelet and higher c reactive protein level were found in patients with pe, suggesting the participation of disseminated intravascular coagulation. these factors may contribute to increase pe risk. conclusion: the risk of pe is higher in septic patients with aki than in those with normal kidney function. therefore, because of paucity of evidence, larger studies are needed to understand pe pathway in septic aki and to establish efficient prophylaxis protocols. compliance with ethics regulations: yes. and of these patients ( . %) required intensive care. the lasted were males ( %) and a majority ( %) were younger than years of age. in intensive care patients, only ( . %) had nosocomial infection, majority were community acquired infections ( . %) with ( %) pneumoniae, ( . %) profound abscess, pyelonephritis ( . %), ( %) meningitidis. patients( %) required mechanical ventilation for days ( % ci - ), length of stay in icu was days ( % ci - ) and mortality rate was %. conclusion: hmkp infections lead young patients in intensive care unit in one third of case with a majority of pneumoniae requiring mechanical ventilation and with a high rate of mortality. furthers studies are needed to investigate the role of this particular strain in severity. compliance with ethics regulations: yes. rationale: infections secondary to snakebite occur in a number of patients, and are potentially life-threatening. bothrops lanceolatus bites in martinique average thirty cases per year and may result in severe thrombotic and infectious complications. we aimed to investigate the infectious complications related to bothrops lanceolatus bite. patients and methods: a retrospective single-center observational study over seven years ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) was carried out, including all patients admitted to the hospital due to bothrops lanceolatus bite. clinical and biological data were reported using the dx care, x-plore et cyberlab softwares of the emergency medicine and analyzed. one hundred and seventy snake-bitten patients ( males and females) were included. thirty-nine patients ( %) presented grade or envenoming. twenty patients ( %) developed wound infections. the isolated bacteria were aeromonas hydrophila ( cases), morganella morganii ( cases), group a streptococuss, and group b streptococcus (one case each). patients were treated empirically with third-generation cephalosporin (or amoxicillin/clavulanate), aminoglycoside and metronidazole combinations. outcome was favorable. the main factor significantly associated with the occurrence of infection following snakebite was the severity of envenoming (p < . ). our findings clearly point towards the frequent onset of infectious complications in b. lanceolatusbitten patients presenting with grade and envenoming. conclusion: infectious bite-related complications of bothrops lanceolatus account for approximately % of the cases, with a strong predominance for grade iii and iv. thus, based on the bacteria identified in the wounds; we suggest that empiric antibiotic therapy including third-generation cephalosporin should be administered to those patients on hospital admission. compliance with ethics regulations: yes. rationale: endocrine abnormalities have been reported with varying frequencies, following traumatic brain injury (tbi). few studies have examined the clinical features and outcomes of isolated acute thyrotropic hormone deficiencies after tbi. theaim of the study was to evaluate the early changes in thyrotropic hormone levels after traumatic brain injury (tbi) and to evaluate whether hormone changes are related to outcome patients and methods: we conducted a months long prospective cohort, including all patients admitted to a university hospital icu with moderate to severe traumatic brain injury (tbi), defined as a glasgow coma scale below twelve (gcs < ). blood samples for basal hormone values of thyroid-stimulating hormone (tsh) and free thyroxine (ft ) were obtained on days , , and . tsh serum concentrations were considered normal at > . mu/l; ft at > pmol/l. a thyrotropic insufficiency was defined as low ft and low tsh plasma levels. all patients were screened with a brain mri. patients were also monitored for neurological deterioration, including cognitive decline, convulsive seizures, increase in cerebral edema and brain herniation that were simultaneous to the diagnosis. results: during our study period's, trauma patients were admitted to our icu and met the inclusion criteria. on admission, our patients had a mean age at . ± , a mean injury severity score (iss) at ± , a mean abbreviated injury severity (ais) of the head at . ± . and a mean gcs at ± . of the patients a thyrotropic insufficiency was diagnosed in patients ( %) during the first days. the median delay to thyrotropic insufficiency diagnosis was days. in three of ( %), the thyrotropic insufficiency was nonrecovering during the patient's icu stay and was transient for the rest. none of the patients with acute thyrotropic insufficiency had direct hypothalamic or pituitary lesions on the brain mri. factors associated to the occurrence of acute thyrotropic insufficiency were: the ais of the head ( . ± . vs. ± . , p = . ), cerebral contusions ( % vs. %, p = . ), subarachnoid haemorrhage ( % vs. %, p = . ) and subdural haematoma ( % vs. %, p = . ). thyrotropic insufficiency was associated to neurological deterioration (p = . ) on the day of diagnosis but did not affect icu mortality ( % vs. %, p = . ). in this study, low pituitary-thyrotropic axis hormone levels were found in the acute phase of tbi and were associated to neurological deterioration but with no perceived effect on icu mortality. compliance with ethics regulations: yes. rationale: acute diabetes insipidus following head injury and its effect on patients outcome have not been sufficiently evaluated in large prospective studies. the aim of this study was to determine the incidence of acute cdi, delay of onset predictive factors and its impact on tbi patients. we conducted a prospective cohort, including all patients admitted to icu with moderate to severe tbi, defined as a glasgow coma scale (gcs) below twelve. for each tbi patient plasma sodium was measured daily, and if abnormally high, urine specific gravity and osmolality were measured. cdi was diagnosed using the seckl and dunger criteria. acute cdi was defined as cdi diagnosed in the first week following injury. all patients were screened with a brain mri. results: during our study's period, trauma patients were admitted to our icu, presented with moderate to severe tbi and were included. on admission, our patients had a mean age at . ± , a mean injury severity score (iss) at ± , a mean abbreviated injury severity (ais) of the head at . ± . and a mean gcs at ± . twenty-three percents ( patients) of the patients developed hypernatremia and % ( patients) were diagnosed with acute cdi. in of ( %), the cdi was nonrecovering. the median delay to develop transient cdi was h and for non-recoviring cdi was h (p = . ). none of the patients with acute cdi had direct hypothalamic or pituitary lesions. factors associated to the occurrence of acute cdi were: younger age ( ± vs ± , p = . ), neuro-surgery ( % vs. %, p < . ), hemorrhagic shock ( % vs. %), p < . ), cerebral edema ( % vs. %), p < . ), and fractures to the base of the skull ( % vs. %, p = . ). patients who developed cdi had a significantly higher mortality than those who did not ( of ( %) vs. of ( %), p < . ). there were no difference in terms of mortality between non-recovering and transient cdi ( % vs. %, p = . ), similarly the onset of cdi did not affect mortality ( h vs. h, p = . ). patients with acute cdi had poor glasgow outcome scale ( ± . vs. . ± . , p < . ) and longer icu los ( ± vs. ± , p = . ). conclusion: acute cdi is associated with higher mortality and poor outcome. therefore it is essential to diagnose and treat it promptly and correctly. compliance with ethics regulations: yes. acute glucocorticoid deficiency following traumatic brain injury mariem dlela, rania ammar zayani, abir bouattour, najeh baccouche, mounir bouaziz habib bourguiba hospital, sfax, tunisia correspondence: mariem dlela (mariem @gmail.com) ann. intensive care , (suppl ):p- rationale: published data demonstrates that long-term hypopituitarism could be common after traumatic brain injury (tbi).however, few studies focused on radiological, clinical, and repetitive endocrine assessment in the acute phase. the aim of the study was to evaluate the early changes in the adrenal axis following (tbi) and to evaluate whether hormone changes affect patient's outcome. we conducted a prospective study, including all patients admitted to a university hospital icu with moderate to severe traumatic brain injury (tbi), defined as a glasgow coma scale below twelve (gcs < ). each patient underwent sequential measurement of plasma cortisol (pc) on days , , and after tbi. we defined adrenal insufficiency as pc less than ng/ml. patients who received glucocorticosteroid therapy were excluded. outcome was measured by incidence of death, and glasgow outcome scale (gos) on day thirty. souhila sadat, dalila zeghdoud, dalila bougdal, kamel guenane ehs salim zemirli, alger, algeria correspondence: souhila sadat (sadatsouhila@hotmail.fr) ann. intensive care , (suppl ):p- rationale: the renewed interest in the pathophysiology of severe traumatic brain injury (tcg), allowed the understanding of the pathophysiological mechanisms leading to neuronal death.the non-invasive, easy, patient-based technical dtc allows evaluation of cerebral blood flow. purpose of the study: to determine the contribution of transcranial doppler (dtp) in the prevention of post-traumatic ischemia. patients and methods: a monocentric, observational, prospective study over a period of years, including tcg in the monitoring of cerebral blood flow (dsc) was provided by the dtc. we collected the following data: age, gender, lesion mechanism, lesion association, glasgow score at admission, time to perform the initial scan, time to perform the initial doppler, various abnormalities found at the initial dtp, the analysis of the level of map according to each situation of cerebral blood flow, the proposed therapies, the time to obtain a correct dtc. ( %), the statistical analysis showed no difference between the delay in setting up a hypohemia and the presence of a correct cerebral blood flow (p = . ), the statistical analysis of the map in the dtc group hypohemia compared to the correct dtc group objectified the absence significant difference between the two groups. the realization of dtp allowed therapeutic prioritization, the introduction of norepinephrine was in % of cases, osmotherapy in % of cases, optimization of sedation in . % of cases, the introduction of penthotal in . % of cases and the completion of decompressive in . % of cases. statistical analysis of mortality showed a significant difference in mortality (p = . ) in the hypohemic dtc group compared with the correct doppler . conclusion: ttc is an essential monitoring tool of cerebral hemodynamics, which may in prove the neurologic outiome of tcg. compliance with ethics regulations: yes. rationale: hyponatremia is a frequent electrolyte disturbance in hospitalized patients. it is particularly common in brain-injured patients with significantly elevated morbidity and mortality. the aim was to study the prevalence of hyponatremia in the acute phase of post-traumatic cerebral aggression, its degree of severity, its predictive factors as well as its prognostic impact in the population of post-traumatic brain injury. patients and methods: this is a retrospective study, carried out over a period of years about all traumatized head patients who developed hyponatremia during the first h of their stay. the descriptive part treated all patients who developed hyponatremia by detailing its different stages of severity.the analytical part treated the patients who developed a hypo-osmolar hyponatremia with a threshold of mmol/l retained to define the severity. during the study period, the incidence of hyponatremia in head trauma patients was . %. the occurrence of hyponatremia was associated only with the occurrence of early seizures (p = . ).severe hyponatraemia was associated with paroxysmal occurrence (p = . ), mass effect (p = . ), and hemostasis disorders. the multivariate study revealed that severe hyponatremia was associated with the glasgow score (p < . ) and pupillary changes (p = . ). on the other hand, it is the initial variation in serum sodium that was associated with both the severity of the initial neurological examination; glasgow (p < . ), saps (p = . ), pts (p = . ) and prism scores (p = . ), haemodynamic instability (p = . ) and neurovegetative disorders (p = . ). lesional features have also been found.regarding the prognosis, the occurrence of initial hyponatremia had a protective effect: a more favorable gos score p = . and a lower mortality (p = . ). a poor neurologic prognosis as well as a high mortality were associated with the most severe hyponatraemia and particularly with the initial variation of the sodium level (p = . ;). the mortality was . %. it was also particularly related to the initial change in sodium levels (p < . , . ). we concluded that there is no association between post traumatic early hyponatremia and the severity of the initial clinical presentation. however, the depth of hyponatremia and especially the initial change in sodium levels have been associated with more severe clinical pictures and a more limited prognosis. compliance with ethics regulations: yes. rationale: post-traumatic epilepsy (pte) is one of the complications described in the aftermath of headtrauma. its incidence is variable in the literature because of its clinical polymorphism. objectives of the study was to analyze the epidemiological profile (clinico-biological, radiological, therapeutic and evolutionary) of the patients having presented pte and to determine the risk factors for this pathology by comparing them with the rest of the traumatized brain patients. patients and methods: our study was retrospective. it was conducted in the intensive care unit (icu) of our university hospital between and . were included in our study all patients admitted to the service with brain injury and a glycaemia above mmol/l during the first h post-trauma. results: the incidence of pte was . %. ( among ) the average age was . ± . years. the sex ratio was . . the average of gcs was . ± . . three ( . %) patients had initial motor impairment. seizures were observed in ( . %) patients during the first h of hospitalization. the mean delay of occurrence of pte was ± . months. pte was diagnosed before the end of the first post-traumatic year in patients ( % of cases). the most commonly observed brain lesions were cortical brain contusions ( rationale: electrolytic disorders are common in neuro-resuscitation, especially dysnatremias and dyskalemias. hyponatremias are the most frequent, including the main etiologies: the syndrome of inappropriate secretion of antidiuretic hormone (siadh) and the "cerebral salt wasting" syndrome (csw). diabetes insipude of central origin secondary to a lack of dha secretion is the second most common disorder. patients and methods: it is a prospective study, analysing all the brains injured admitted to the a intensive care unit of chu hassan in fez, morocco. study spread over a -month period from / / to / / . the objective of the study is to detect the most frequent hydro-electrolytic disorders and to evaluate the therapeutic effectiveness of the service protocols. results: all these brains injured have caused he disorders over a period of time varying between d and d : * cases of hyponatremia ( %)/ cases of hypernatremia ( %), * cases of hypokaliemia ( %)/ cases of hyperkaliemia ( %), * cases of hyperchloremia, or %/ cases of hypochloremia ( %). * cases of diabetes insipidus, or . %. * cases without he disorder ( . %). the treatment for these disorders was: *for hypona; it reached mmol/l, initially corrected by a -hour water restriction, followed by an increase in the basic ration and furosemide boluses according to the ecv, even sodium loads for a single case of salt loss syndrome, while the main etiology remains the siadh. *for hyperna, it has reached mmol/l, evaluated by the extracellular volume, corrected by enteral tap water after calculation of the hydric deficit. if hperna is associated with polyuria greater than cc/kg/h; we speak of: *insipude diabetes, with polyuria up to cc/kg/h, compensated with potassium-containing solutions and blood ionogram monitored every h. desmopressin was used in titration, by bolus of . µg, with a diuresis objective between and . ml/kg/h. *for hypokalemia, up to . g/dl, observed mainly in the acute phase of brain aggression, corrected by increase in br for a k between . and g/l, and by potassium loads if k below . g/l. the evolution: deaths or . % ( cases of uncorrected diabetes insipidus), the restriction of disorders were corrected. conclusion: a knowledge of the hydroelectrolytic disorders encountered in this context is essential, as well as the implementation of a diagnostic and therapeutic protocol, which will reduce the time required to correct these disorders. compliance with ethics regulations: yes. . ] u/h). however, workload was increased under star ( vs. measurements per day), as expected from measurement interval difference between star ( -hourly) and the sp ( -hourly). conclusion: this unique patient-specific risk-based dosing approach gc framework was successful in controlling all patients safely and effectively. these preliminary results are encouraging and show gc can be achieved safely and effectively at lower target bands. in turns, these improved gc outcomes could improve patient outcomes. compliance with ethics regulations: yes. rationale: although its incidence has declined in recent years, gastric cancer remains common worldwide and is the leading cause of gastrectomy. his treatment is mainly surgical, but his prognosis remains poor. many studies on survival and prognostic factors have been carried out in foreign series. patients and methods: this is a retrospective study covering a period of three years from january to december interesting patients who had a gastrectomy and hospitalized in emergency resuscitation department surgical uhc ibnou rochd from casablanca. the statistical analysis of the different clinical, paraclinical and therapeutic data was carried out thanks to an exploitation sheet. rationale: gram-negative bloodstream infections (gnbsi) require timely appropriate antimicrobial therapy in intensive care units (icu) patients. conventional techniques usually take - h for antimicrobial susceptibility testing (ast). innovative approaches (accelerate pheno ™ system) provide pathogen identification in ~ h and ast including minimal inhibitory concentrations (mics) in ~ h. we report, in icu patients with gnbsi, results of implementation of the accelerate pheno ™ in our laboratory. we prospectively screened all gnbsi episodes reported in adult icu patients between september and september . to allow integration into the laboratory workflow, the accelerate pheno ™ was run on blood bottles positive before am (day ), in parallel with routine procedures: maldi-tof identification after short incubation on solid media (day ), β lacta (bio-rad ® ) test (day ) and disk diffusion method for ast (day+ ). for each episode, antimicrobial regimen was reassessed by a multidisciplinary team of bacteriologists, infectious diseases and icu physicians by the end of day . we measured: (i) concordance of accelerate pheno ™ results with conventional techniques, (ii) number of antibiotic adaptations on day and (iii) number of patients within the therapeutic range (free fraction over x mic and below concentration at risk of adverse events), based on real-time measurement of beta-lactams concentrations. results: of patients reported with gnbsi over the study period, were included. mean age was of ± . years, / were males. main sources of gnbsi were pulmonary (n = ) and digestive (n = ). bacterial identification of the accelerate pheno ™ was concordant with standard techniques in ( %): enterobacteriacae (n = ), pseudomonas aeruginosa (n = ). overall categorical agreement for ast was of % ( errors including very major errors). by the end of day , the antibiotic regimen was de-escalated in ( %) patients, which was appropriate in ( %). in cases, de-escalation was possible, but not fulfilled by icu physicians. twenty patients had beta-lactams concentrations measurements: were in the therapeutic range, below and over. conclusion: accelerate pheno ™ provided rapid and accurate results for most microorganisms isolated in blood cultures of icu patients with gnbsi. however, in a laboratory with routine maldi-tof early identification and β lacta test performed on day , the impact on early adaptation of the antibiotic regimen was evident in around patient over . compliance with ethics regulations: not applicable. jean-luc baudel , jacques tankovic , redouane dahoumane , jean-remy lavillegrand , razach abdallah , geoffroy hariri , naike bige , hafid ait-oufella , nicolas veziris , eric maury , bertrand guidet service bactériologie, hôpital saint-antoine, paris, france; service réanimation médicale, hôpital saint-antoine, paris, france correspondence: jean-luc baudel (jean-luc.baudel@aphp.fr) ann. intensive care , (suppl ):p- rationale: evaluation of the accurateness of the accelerate phenotest bc kit for rapid analysis ( . h for microorganism identification and additional hours for antibiotic susceptibility testing) of positive blood cultures from icu and hematology patients. patients and methods: from february to august , we included patients from the icu and hematology units with positive blood cultures. the following informations were collected : gender, age, duration of prior antibiotherapy, source of the infection, results obtained by conventional microbiological methods and by phenotest (data obtained and time to obtention of results). informed consent was obtained from all patients. results: blood cultures were analyzed in patients (m/f ratio . , age . ±, from the icu and from hematology). % of the patients were receiving antibiotics at the time of blood culture collection (mean duration : . days). the source of infection was unknown in % of cases, urinary in %, catheter-related in %, ascites in %, pneumonia in %. in cases ( %), there was a perfect match between phenotest and conventional results (identification and antibiotic susceptibility testing). in cases ( %), the bacterium responsible was not present in the phenotest panel. in cases ( %), phenotest identification was correct, but some discrepancies were observed regarding antibiogram. in cases ( %) phenotest identification was again correct but no antibiogram was available. in cases ( %), where two bacteria were present, phenotest could not identify one of them. in cases, phenotest did not provide bacterial identification because too few bacteria were present in the blood culture bottle. conclusion: the phenotest panel covered % of the bacteria implicated in this study. when the bacterium responsible was present in the panel, the results given by the phenotest correlated in % of cases with those of conventional methods. some rare discrepancies were observed regarding antibiotic susceptibility testing that have to be analyzed further. in the remaining % of cases, where too few bacteria or two different bacteria were present in the blood culture bottle, technical limitations did not permit to correctly identify microorganism(s) present or to obtain an antibiogram. compliance with ethics regulations: yes. mélanie fromentin, antoine bridier-nahmias, constance vuillard, jean-damien ricard, damien roux inserm umr iame infection antimicrobials modelling evolution, paris, france correspondence: mélanie fromentin (mel.fromentin@wanadoo.fr) ann. intensive care , (suppl ):p- rationale: studying human lower respiratory tract microbiota by using ngs (new generation sequencing) method is complex because of many unexpected biases due to dna extraction and amplification procedures. lung microbiota evolution under mechanical ventilation evolution may be highly informative to evaluate the actual risk of vap (ventilator-associated pneumonia) development. before starting a large study on the lung microbiome of ventilated icu patients, a methodological study was mandatory. patients and methods: five control and three vap patients were selected. endotrachealaspirate (eta) and oropharyngeal swab (os) were collected at icu admission for control patients and, days before and on the day of vap diagnosis for vap patients. after automated extraction of total dna, hypervariable region v of the s rdna genes was amplified with two different pairs of primers f- r: oligonucleotides from the earth microbiome project (earth primer pair) and from the gut microbiome project (gut primer pair), followed by sequencing on illumina miseq plateform. after bioinformatics analysis with mothur ® software, we compared the performance of ngs alongsideconventional bacterial culture. differences in alpha diversity (microbial diversity in a sample), expressed as the shannon index, across respiratory tract site (upper or lower) and across time (before and at vap time) has been investigated. a positive control (pc), rationale: colistin is used as a last-line treatment to combat multidrug-resistant (mdr) gram-negative bacilli (gnb). worryingly, colistin resistance in klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumannii is increasingly reported worldwide. we hereby report the prevalence of colistin resistance among gnb isolated from burn patients in tunisia. the study was carried out on strains of gnb isolated from microbiological samples of burn patients hospitalized in the intensive care unit between october and december . identification was performed by conventional methods. antimicrobial susceptibility was tested by disk diffusion method and the results were interpreted according to ca-sfm guidelines. minimum inhibitory concentration (mic) of colistin was determined using the eucast broth micro-dilution method (umic, biocentric ® ) results: pseudomonas aeruginosa was the most frequently isolated bacteria ( strains), followed by acinetobacter baumannii ( strains) and klebsiella pneumoniae ( strains). the most common sites of isolation were blood cultures ( %), catheters ( %) and skin samples ( %). most of p. aeruginosa isolates were multidrug-resistant with high levels of resistance to imipenem ( . %), ceftazidime ( %) and ciprofloxacin ( . %). however, all of them were susceptible to colistin. in fact, mics of colistin against all p.aeruginosa isolates were less than or equal to . mg/l. a. baumannii strains had high resistance rates to beta-lactams : % to ceftazidime and % to imipenem. only one strain was resistant to colistin with a mic equal to mg/l. all k. pneumoniae isolates were resistant to extended-spectrum cephalosporins. one third of these strains were resistant to imipenem and more than half ( . %) were resistant to amikacin. two strains were resistant to colistin with high mics (> mg/l). both were carbapenemase-producers, carrying oxa- and ndm carbapenemase encoding genes. conclusion: these data suggest that colistin-resistant or pan-drug resistant gnb clinical isolates are still relatively rare. however, they have important global public health implications because of the therapeutic problems they present, especially for vulnerable populations such as severely burned patients. hence the need to test colistin regularly in the laboratory and to set up a monitoring program for mdr pathogens. compliance with ethics regulations: yes. rationale: descending necrotizing mediastinitis (dnm) are medicosurgical emergencies whose forecast is closely related to the precocity of the therapeutic assumption. the purpose of our work is to profile these patients as well as the therapeutic and evolutionary aspects. patients and methods: retrospective study over years in the intensive care unit of the hospital august. all patients with dnm on cervicofacial cellulitis were included. results: cases were collected, % of cellulitis, incidence of . patients / year. average age , sex ratio of . . smoking, chronic alcoholism and diabetes are the most common antecedents. the favoring factors were: (poor dental conditions: % of cases, non steroidien anti-inflammatory drugs: %, diabetes: %). in % of cases the front door was dental. average time taken to take care of days. c-reactive protein and procalcitonin were positive in all patients. in % the chest x-ray was normal. all patients received tri-antibiotic therapy. intubation were difficult in all patients, we used nasofibroscope in % of cases and a rescue tracheotomy in one patient. only one patient had a cervico-thoracic surgical approach; for all the others she was cervical alone. streptococcus was the most isolated germ. the complications were (septic shock: %, ards: %). the average hospital stay was days with a mortality rate of %. conclusion: dnms are poorly prognostic. the best treatment remains prevention by better management of dental abscesses and tonsillar phlegmons. rationale: the initial, empirical antibiotic therapy of ventilator-associated pneumonia (vap) is often based on timing of its occurrence in relation to the onset of mechanical ventilation. this is due to reported differences between causal pathogens associated with early-onset (e-vap < - days of mechanical ventilation) compared to late-onset vap (l-vap ≥ - days of mv). e-vap is most often reported to be due to antibiotic-sensitive pathogens while l-vap is frequently attributed to antibiotic-resistant pathogens. however, there is emerging evidence that the isolated microorganisms may be similar regardless of onset time. the aim of our study was to compare the clinical outcomes of critically ill patients developing e-vap and l-vap and to compare the causative pathogens of the two groups. patients and methods: all the patients with the diagnosis of vap admitted between january and december were retrospectively included. vap was suspected on the basis of clinical and chest x-ray findings. the identification of the causative organisms was performed with endotracheal aspirate (eta) cultures. results: ninety patients developed vap. e-vap was observed in patients ( , %), whereas patients ( , %) developed l-vap. among patients with early-onset vap, % received antibiotics prior to the development of pneumonia, compared to % with late-onset vap (p = . ). otherwise, no differences (sociodemographic factors, antecedents, severity score, length of stay, length of mv) between the two groups were observed. the most common pathogens associated with e-vap were enterobacter species ( . %), pseudomonas aeruginosa ( . %) and oxacillin-resistant staphylococcus aureus (orsa , %). enterobacter species ( . %), acinetobacter baumannii ( . %) and pseudomonas aeruginosa ( %) were the most common pathogens associated with l-vap. no difference was noted in the contribution of multidrug resistant bacteria mdr ( % vs. %). hospital mortality was significantly greater for patients with l-vap caused by mdr ( %) compared to patients with e-vap ( %) (p = . ). conclusion: this classification is no longer helpful for empirical antibiotic therapy, since both early-onset and late-onset vap were caused by mdr bacteria. this justifies the need of intensive care unit-specific knowledge of causal agents associated with vap to reduce the rate of administration of inadequate antimicrobial therapy. compliance with ethicsregulations: yes. key: cord- -ak pq authors: nan title: th european congress of intensive care medicine athens - greece, october – , abstracts date: journal: intensive care med doi: . /bf sha: doc_id: cord_uid: ak pq nan objectives: evaluate the levels of tnf, il- and pai-i in different moments of the ards and the possible relationships among them. methods: septic patients with ards were studied. also significant differences for: tnf, pai-i and il- in septic patients and both evaluations of ards with control gropup; pai- between septics and nd evaluation in ards, and between the ist and nd evaluation in ards; il- between septics and both evaluations in ards; and il-~ in both evaluations in ards patients in relation to mortality. conclusions: i) elevations of tnf, pai-i and il- , with clinical signs, are suggestive of infection; ) the persistent and progressive elevation of pai-i with any clinical criteria may suggest evolution to ards; ) due to its own kynetics, il- takes part later in the acute phase, its levels being related to the magnitude of the injury in the tissues. objectives: the influence of long-term volume therapy with different solutions on plasma levels of circulating adhesion molecules was studied. methods: according to a randomized sequence, patients with sepsis secondary to major surgery exclusively received either hydroxyethylstarch solution ( % hes, mean molecular weight (mw) , daltons, degree of substitution (ds) . ) or human albumin % (ha) for volume therapy for days. plasma levels of circulating (soluble) adhesion molecules (endothelial leukocyte adhesion melecule- [selam -i] , intercellular adhesion molecule- [sicam -i] , vascular cell adhesion molecule- [svcam -i] , and p-selectin ) were serially measured on the day of admission to the intensive care unit (='baseline ' value) and during the next days. results: selam-i, sicam-i, and svcam-i plasma levels were markedly higher than normal at baseline in both groups. in the hes-patients, selam-j decreased to normal range, whereas it further increased in the ha-group (from • to • during the study period, sicam-i and svcam-i plasma levels remained unchanged in the hes-patients, but further increased in the ha-group (from • to , • sgmp- increased significatly only in the ha-group ( • to • only pao /fio was significantly correlated to plasma levels of adhesion molecules. conclusions: sepsis is associated with markedly elevated plasma levels of adhesion molecules indicating endothelial activation or damage. by long-term volume therapy with hes, these levels remained unchanged or even decreased, whereas volume therapy with human albumin did not have any beneficial effects on soluble adhesion. central venous catheters are frequently used in the care of the critically ill patient. the incidence of catheter related sepsis varies in the literature. we investigated the occurrence of contamination and sepsis compared to results of the epic study as part of quality assesment in our intensive care unit. from january until august all removed central venous catheters were examined for microbiological culture. the patients who showed signs of sepsis were also registered. the results of the contaminated catheters and septic patients were compared with results from the epic study. during the month period , patients were hospitalized on our intensive care unit. central venous catheters were examined for microbiological culture. specimens appeared to be possitive ( %). patients showed clinical signs of sepsis. the incidence of sepsis due to contaminated central venous catheters was / ( %). the incidence of sepsis due to the presence of all central venous lines was / ( %). the microorganisms responsible for the sepsis syndrom were : stapylococcus aureus (n= ), escherichia colt (n= ), others (n= ). in the epic study the percentage for sepsis on the icu was . % for the netherlands and . % for europe. despite a high number of positive culture from removed intravascular lines, a low percentage of sepsis was seen compared to results of the epic study. we recommend routine bacteriological culture of all removed central venous lines and recommend to look at colonization and sepsis due to intravascular lines as a measure of quality control in the intensive care unit. objectives: prognostic assessment of simplified acute physiology score (saps) in granulocytopenie patients with septic shock (ss). methods: the medical records of admissions to an intensive care unit (icu) of granuloeytopenic patients with ss are reviewed. fiftytwo patients had haematological malignancies. seven patients had aplastie anaemia. patients were categorised as survivors (discharged from icl and non-survivors (died in the icu). saps index was calculated for patients daily during their stay in icu. all patients were severe granulocytopenic (total white cell count less than , ] ] ). results: five patients ( , %) were discharged from icu. fifty-four patients died in icu. non-survivors had saps on admission higher than survivors ( . + . and . + . , respectively, p< , , mann-whitney u test). no patient with a saps greater than survived. mortality among the patients with saps from to was , %o. the evolution of ss was rapid. the mean stay in icu among non-survivors was only hours. an analysis of the saps index on admission of non-survivors showed an inverse correlation with the duration of their stay in icu (r=- , , p= . ). all survivors recovered from granulocytopenia. they had normal white cell counts at the time of discharge from icu. there was inverse correlation in survivors between saps and white cell counts, when these parameters were evaluated daily. however, the saps index alone cannot be considered to be on individual predictor factor of mortality. patients who had failure of the malignancy to respond to chemotherapy and who had persistent granuloeytopenia died in icu despite saps index on admission and recovery from ss. conclusion: saps index greater than , failure of the malignancy to respond to chemotherapy and persistent leueopenia all point to a poor outcome of granulocytopenie patients with ss. introduction: antipyretics sometimes are used for fever control in febrile neutropenic patients with hematological malignancies(hm). we observed a dramatic fall of blood pressure(bp) and development of septic shock(ss) in some of the patients who received antipyretics. aim: to clarify can antipyretics provoke ss in neutropenic patients with infection. methods: retrospective review of medicat records of neutropenic(wbc < , / )patients with hm, admitted to the intensive care unit for ss, was performed. there was selected group of patients receiving antipyretics shortly before a fall of bp. results: there was a definite causal relationship between receiving antipyretics and fall of bp in from patients. all patients had fever due to infection and had normal level of bp before receiving antipyretics. hypotension developed within minutes up to , hours after administration of antipyretics. three patients received , g of metamisol and one , g ofparacetamol per os. in all cases we observed dramatic diaphoresis and the temperature fall to subnormal level ( . + . ~ accompanied'by hypotension. but in - hours the fever was coming back without blood pressure elevation. the fluid replacement was controlled by central venous or wedge pressures. there were required + ml colloid and cristalloid solutions for volume loading. in spite of fluid administration the hypotension persisted and all patients required inotropic therapy. only one patient survived and is alive now. conclusion: it seems to us that our data offer to state that antipyretics administration can initiate ss in febrile neutropeuic patients with infection. objectives: to assess the agreement between cardiac output (co) measured by odm t and by other methods used in icu patients. methods: we prospectively studied adu t patients requiring hemodynamic monitoring with a pulmonary artery catheter. an esophageal doppler monitor provided measurements of co (odm), stroke volume and flow time (ft) used as an indirect evaluation of patient's volume status. patient hemodynamic status was evaluated by a modified fast response pulmonary artery catheter (baxter health care corporation, santa ana, ca), allowing co measurements by thermodilution "d) and an evaluation of right ventricular ejection fraction and end diastolic volume (rvef and rv-edv). in the last six patients co was measured by transthoracic echocardiography (echo) and oxygen consumption was measured by a deltatrack ii metabolic monitor (datex) allowing co calculation according to the fick formula (fick). the agreement between methods measuring co and their reproducibility, were evaluated by bland and altman analysis. results: agreement between co measurements is expressed as bias (d) and % limits of agreement (l of a = d_+ sd . td-fick - . - . to . fick-echo . - . to . there was no correlation between ft and rv-edv. conclusions: although co measurements by odmil had the best reproducibility, the limits of agreement between the four methods tested were unacceptable for clinical purposes. further investigation is required in order to improve the accuracy of co measurement in the icu. phd, a. paltzev, v.bajbikov, b.dobryakov d.sc., a.ostanin phd, o.leplifia phd, h.chernykh phd munieip. hosp. n l, n ; inst. of clin. immunol., novosibirsk, russia objectivies: efficiency of native cytokines used in the treatment of patients with severe surgical infections has been studied. methods: for two years patients were treated with cytokine mixture (ssp) obtained by arterio-venous perfusion of swine spleen and contained the following cytokines: il- , il- , il- , tnfa, ifny, gm-csf. results: ssp intravenous infusions were shown to accompany with mortality decrease from . % to . % in patients with abscessed pneumonia and lung abscesses and from % to % if disease course was complicated with sepsis. in patients with purulent peritonitis and sepsis efficiency of ssp was decreased due to endotoxieosis. thus, we used adoptive immunotherapy with mnc activated in vitro with ssp or recombinant il- . intravenous infusions of such cells resulted in transformation of a pathologic process from destructive into productive one. moreover, clinical manifestations of sepsis were controlled in % and mortality was decreased from % to %. conclusions: the use of eytokines themselves as well as cytokine-treated lymphoeytes permits to control the disease and leads to the mortnlity decrease owing to stimulation of host defence mechanisms. background: although red blood cell transfusions (rbct) are used to increase oxygen availability in septic patients, several lines of evidence suggest that rbct may actually worsen tissue hypoxia. thus, rbct may negatively influence outcome of septic patients. objectives: to determine the association of ) rbct ; ) number of units transfused; and ) mean age of the units transfused on the first day of transfusion with mortality of critically ill septic patients. methods: we prospectively identified patients who met strict criteria for sepsis syndrome (ss) seen in the icu of st. paul's hospital from to and excluded patients who died in the first days after the onset of sepsis. we recorded clinical characteristics, multiple system organ failure score, and apache ii at onset of sepsis. then, we retrospectively recorded the total number and age of rbc units transfused during the first days after onset of sepsis. overall -day mortality was %. results: the main results are shown in the table. the mortality of patients who received rbct was nearly double the mortality of those who did not receive rbct even after adjusting for severity of illness using apache ii. objectives: gastric mucosal acidosis is frequently observed in patients with sepsis. the aim of this study was to determine whether volume infusion using pentaspan| decreases abnormal gastric mucosal pco (pico ) in patients who have sepsis syndrome (ss) who have already been resuscitated using clinical endpoints. methods: we prospectively identified patients who met strict criteria for ss, had a pulmonary artery catheter and a gastric tonometer in place, and pico > mmhg. pentaspan| ( ml) was infused in rain. measurements of hemodynamics, hemoglobin, arterial lactate, blood gas analysis, and pico were performed before and repeated miff and hr after pentaspun| infusion. we calculated the pico -arterial pco' difference (pico -paco ) and phi (using henderson-hasselbach equation). anova was used to assess statistical significance. results: all patients werereceiving adrenergie drugs. map was : : mmhg and lactate . : : . mmol/l. pentaspan| increased ci by % (p< . ) but did not change pico ( and increase m oxygen o* wery were simimny achieved in both groups. nevertheless, epinephrine was associated with a lactic acidosis and increased laetate/pyruvatemia ratio (l/p) that evoke a dysoxia rather than a metabolic effect. an higher gastric mucosal pco in the ep group compared to nor-rob suggests the hypothesis of an anaerobic production of co in favor of a splanchnic hypoxia. in both group, arterial ketone body ratio that reflects hepatic mitochondrial redox state, compared to a control group without shock was decreased but increased between and hours after restoration of arterial pressure. the association norepinephrine-dobutamine seems to be better for splanehnic circulation than epinephrine and should be used for dopamine resistant septic shock. moreover, the increase in arterial pressure with nor-dob improved gastric mueosal ph and hepatic mitochondrial redox state and argue to reconsider arterial pressure as a significant goal for resuscitation in septic shock. conclusion: significantly higher malondialdehyde and ghitathione levels and glutathione-peroxidase activity in group ns at the end of icu stay were related to mortality these findings indicate an increased generation of free oxygen radicals together with increased anfioxidant activity in this group and sapport the employment of antioxidant interventions in critically ill patients. oblecfives: to determine the role of nitric oxide (no) in the mechanism of septic shock induced by isolated limb perfuslen with recombinant tnfcr methods: we have measured tnfr~ and metebo~ites of no in patients with signs ot septic shock following treatment with isolated limb perfusion for nonresectable soft tissue tumors and melanomas of a limb. perfuslen was carried out with melphalan (burroughs wellcome) and recombinant tnfcr (boehringer). tnfc~ was determined by specific radiometric assay (medgenix diagnostics), nitrate and nitrite were measured with a modification of the guess reaction ~. results: results are shown in the table. conclusions: during isolated limb pedusion with recombinant tnf~ very high levels of tnfcr were measured in arterial blood in patients. they all showed signs of severe sepsis syndrome with shock from vasodilafion, probably due to leak of recombinant tnft~ from the peduslen circuit to the systemic circulation. tnfc~-induced vasodilation was not accompanied by a rise in serum no-metsbolites. our findings do not confirm the widely accepted theory, mainly based on animal experiments, that genera• of no is the key pathogenefic mechanism in septic vasodilafion , nor that tnfrt invariably induces forreafion of no. the precise mechanism of shock in these patients remains to be elucidated. references: . moshage h, kok b, huizenga jr, jansen plm nitrite and nitrate determinaiions in plasma: a critical evaluation. clin chem : / . . moncada s, higgs a. the l-argioine-nitrio oxide pathway. n engl j med ; : - ec is a commonly used for prolonged, stable animal anesthesia. noting that the hypotension after iv lps was attenuated by ec, we hypothesized ec also protects against lps toxicity. sprague-dawley rats received ip saline (s), thiobutabarbita mg/kg (tb), or varied doses of ec, followed hours later by bolus mg/kg iv lps. -day survival is shown below: group: s tb ec( . gmikgi ec( .sgm/kg) ec(i. gm/kg) alive (n) t ~ total (n) s s "signiflcant;y different from all other groups, p< . s / rats given lps followed hours later by ec ( . gm/kg) also died. additional rats were treated with s (n= ) or gm/kg ec (n= ) followed by mg/kg lps, then sacrificed at hours. blood glucose (bg, mg/dl),.hematocrit (hct), leukocyte count (wsc/mm~ platelet count (pltxl ~/mm ), bicarbonate (hco, mg/dl), gross bowel hemorrhage (bh, - scale) and lung myeioperoxidase activity (mpo, ~vmirvgm wet lung) are shown below ( we conclude that ec reduces the lethality and multiple organ toxit;~ty of lps. its diverse effects suggest asite of activity upstream from the cytokine cascade. these results are important for studies of lps which may use ec anesthesia and may have potential in the therapy of septic shock. [zo = hz impedance (z; {dyn.sec.cm " }); zl = first harmonic z; zc = characteristic z; z ph. = t'trst harmonic phase angle {radians}; f, #, * at least p < . between fio . and . , fio . and fio . &no - . _+ . - . _+ . # - . + . m - . + . * - . + . * - . + . * - . _+ . * in hyperoxia, compared to dogs at the same q, minipigs had a higher ppa ( + rnmhg versus + mmhg; p < . ). hypoxia increased (ppa-ppao) at all levels of q by an average of mmi-ig in minipigs and mmhg in dogs. inhaled no inhibited hypoxia-induced (ppao-ppa)/q changes in both species. conclusions: we conclude ~ that the minipig is an animal model of elevated pulmonary vascular resistance and impedance, and ~ that hypoxia-induced alterations in pvz spectrum are due to changes of resistance in small arteries. objectives: ) to determine the toxicity of ng-monomethyi-larginine (nma) administered by intravenous bolus to patients with refractory septic shock. ) to investigate the biologic activity of nitric oxide synthase inhibitors in septic shock. methods: from august to january , thirteen patients with vasopressor refractory septic shock received nma intravenously in escalating doses from to mg/kg. results: no hepatic, renal, gastrointestinal, or hematologic toxicity was observed at doses of nma as high as mg/kg. significant biological activity was observed at all dose levels consisting of increased blood pressure (systolic blood pressure from . mm hg + . to . _+ . s.e.m., p= . , systemic vascular resistance ( + to + dyne.sec/ cm s, p=. ), and a decrease in vasopressor requirements. the magnitude and duration of these effect were dose dependent. decreased cardiac output ( . _+ . to . _+ . i/min p=. ) and increased pulmonary artery pressure ( . _+ . to . _+ . mm hg; p=. ) were also observed. no significant effects on heart rate, pulmonary capillary wedge pressure, or central venous pressure were observed. four of patients survived for more than days, patients died of cancer complications (all patients had maintained blood pressure for h on nma) and patients died of complication attributable to septic shock (mods, ards, dic, refractory hypotension), and patient was unevaluable. conclusions: no adverse clinical effects have been observed in patients receiving bolus doses of nma as high as mg/kg. the increased pulmonary artery pressures observed in septic shock patients is further augmented by nma and may limit the dose which can be administered by intravenous bolus. other schedules of drug dosing may attenuate this effect. glucose-insulin-potassium (gik) solutions have been shown to improve cardiac contractility and increase oxygen availability in experimental and clinical settings of septic shock. several mechanisms have been proposed to explain these effects including a direct improvemeut of the energy balance by glucose, a direct influence of insulin on cardiac performance or an increase in intravascular volume due to the hyperosmolarity of the solution. to explore the role of hyperosmolapity, we compared the effects of gik to those of a isoosmolar hypertonic saliue solutiou in endotoxin shock in dogs. methods : the study included mongrel dogs ( • pentobarbitalanesthetized aud mechanically ventilated with air. thirty minutes after the intravenotls administration of mg/kg of e. coli endotoxin, the dogs were randomized to receive a ml/kg infusion in rain of a hypertonic ( mosm]l) solution iucludiug either a mixture of glucose % with u insulin and meq kcl/l (glk-group ) or hydroxyethyl starch . % in naci . % (hes-group ). in each dog, a . % saline infi~sion was continued to maintain the puhnonary arlery occluded pressure at baseline level. hemodynamic, blood gas aualysis and laboratory data were collecled at baseline and miu, rain, rain, and nunutes later.. results : eudotoxin administration was followed by a fall in mean arterial pressure (map) aud cardiac index (ci) and a rise in blood lactate levels. resuscitation with either gik or hes hypertoaic solutions resulted in similm increases in map, ci, oxygen delivery and left ventricular stroke index (table ) . we conclude that during resuscitation from endotoxic shock the use of gik solutions is not superior to hypertouic hes solutions. the higher blood lactate levels observed in the dogs receiving gik can be attributed to the glucose metabolism. , for group , for group ) were drawn and immediately analysed at ~ using the abl radiometer for po , pco and ph, and the osm radiometer for hbo %, hbco% and methb%. psost (i.e. the ps at ph= . , pco = mmhg and temperature at ~ c) was calculated automatically by the instruments on mixed venous blood, as was the ps "in vivo" (i.e. the ps at the patient's value of ph, pcoz and temperature), using siggaard-andersen's algorithm. the data were compared by the one-way anova test and by the t-test for paired and unpaired samples. results: the mean resulting values (in mmhg) with the statistical differences are shown in table i. in addition, the time series analysis shows the mean ps~st values as statistically below the psin vivo" in the septic patients while the opposite is shown for the cardiac patients. no differences in the time analysis are demonstrated for the second group. a possible clinical significance may be drawn from these different behaviours. objectives:toxemia degree and humoral immunity condition have been studied in patients aged from to with progressive course of sepsis and polyorganic insufficience. methods: such toxemia and humoral immunity findings as lencositlcindex of toxication (lii), level of oligopeptides of the middle molecular mass registered at the wave length of nm(mmi) & nm (mm ), distribution index (id), immunoglobulins a,m,g, concentration of circulating immunocomplexes (cici & cic ) and also some clinical and biochemical findings on the , , day after the operation serve as criteria for treatment effect. results: it was founded that in intensive therapy and detoxication, level of lii is successively decreased from . ~ . to . +. on the -th day after the operation. true decrease of the level mm from . ~. to . +. un & optimal density and increase of distribution index from . to . are argued. conclusions: in studlng the dynamics of the immunoglobulin's spectrum and the true increase of immunoglobulin g level from . +. g/i to i . +. g/i on the -th day after the operation simultaneously with the decrease of cic from . ~ to . ~ . (p . ) were founded. some stages of the investigation true increase of lymphocytes from . + . % to . + . % was noted and it appeared to be a favourable prognosis finding for disease outcome. high correlation dependence between bacillus-and segmentonuclear neutrophils and immunoglobullns g & m (r=. -. in p<. ) was discovered and it also showed positive dynamics of the course of the disease. a year old male patient was admitted to the icu with severe paraquat poisoning. treatment consisted of gastic lavage and oral administration of fullers earth. because of very high plasma levels hemodialysis together with charcoal hemoperfusion was started within one hour after admission. this treatment was further continued by continuous veno-venous hemofiltration in order to remove the circulating paraquat and also circulating cytokines. nevertheless patient s condition worsened necessitating artificial. ventilation and hemodynamic support. patient died hours after admission of acute multiple organ failure due to paraquat poisoning. serum levels of paraquat were determined by colorimetric method (table) . levels of interleukin (il ) and (il ), tumor necrosis factor (tnf-alpha), interleukin i receptor antagonist (il ra) were determined both in plasma and ultrafiltrate ( q~!ectives : evaluate in critically ill patients the effects of tow-dose dopamine on gastric mucosal blood flow (gmbf) using laser-doppler flowmetry, a continuous non invasive method of assessing microcirculation. methods : patients requiring both mechanical ventilation and pulmonary artery catheterization for multiple trauma (n= ), ards (n= ) and pancreatitis (n=l) were included. in each patient, the laser-doppler (ld) probe was inserted through a naso-gastric tube. the ld signal is proportional to the number of red blood cells moving in the measuring volume and the mean velocity of these cells. when the ld signal was satisfactory, an aspiration was created into a catheter which was fixed in parallel to the ld probe, to maintain the tip of the probe against the gastric wall at the site of measurement. data (systemic hemodynamic parameters and gmbf) were obtained at the end of a rain resting period (baseline), then min after dopamine ( mcg/kg/min) infusion, and finally rain after the end of dopamine infusion (recovery gmbf _+ (perfusion units) gmbf ~a% vs baseline) * p < . vs "baseline" and "recovery". conclusions : ) despite a slight increase in co (+ %), the dramatical increase in gmbf (+ %) with dopamine, strongly suggests a selective vasodilator effect of low-dose dopamine on gasaic mucosal perfusion. ) laser-doppler flowmetry appears a promising method to assess gastric microcircalation in critically ill patients. increasing evidence suggests that the activation of inos is the final common pathway for vasodilation in human sepsis associated with endotoxic shock. activation of the cellular immune system induces the excessive release of the pteridines neopterin (n) and , -dihydroneopterin (nh ) by human macrophages/monocytes. besides the well established diagnostic value of pteridines in several inflammatory diseases, it is speculated that these substances per se exhibit biochemical functions. thus we hypothesize that pteridines can modulate inos gene expression in vascular smooth muscle cells (vsmc) in vilro. cdtured rat aortic vsmc from female wistar kyoto rats were incubated with n ( pm), nh ( ilm), lipopolysaccharide (lps, ~g/ml), and interferone-~/(ifn-~/, u/ml) for h, respectively, inos gene expression was measured by competitive reverse transcription polymerase chain reaction. the results are summarized in the table. the present study demonstxates a neopterin induced increase in inos mrna expression at the transcriptional level in vsmc. while coincuhation of cells with n + lps resulted in an additive effect on inos gene expression, n + ifn- seem to have a more than additive effect nh did not alter inos mrna synthesis, but it suppresses the lps as well as the ifn-yinduced augmentation of inos gene expression. we speculate that this pteridine-mediated modulation of inos gene expression is involved in the regulation of the vascular tone in endotoxic septic shock. the relationship of sepsis and coagulation abnormalities is well known, mainly in severe sepsis and septic shock. still farther, the extreme expression of hemostasis abnormalities (disseminated intravascular coagulation) in sepsis, has been extensively described. we studied the changes in several coagulation and fibrinolysis markers in septic patients, trying to correlate them with the evolution of the sepsis phenomenon, with an emphasis in its early stages, where therapeutic intervention might be more drastic. in patients, with sepsis, with severe sepsis and with septic shock, as well as in healthy volunteers (control group) we measured : platelet (ptl), coagulation markers [fxii, fvii, fviii, fvw, fibrinogen (fibr) we conclude that all parts of the coagulation system are gradually changed during the evolution of sepsis phenomenon , even in the earliest stage of sepsis. the expression of an inducible nitric oxide (no) synthase (inos) plays a major role in the pathophysiology of septic shock (ss). inhibition of inos could therefore be of therapeutic value. however, such an inhibition has been shown to be detrimental, increasing tissue anoxia (and end-organ damage), possibly through the simultaneous blockade of constitutive nos (cnos). thus, selective inhibition of inos might be more suitable. we evaluated the effects of l-canavanine (can), a more potent inhibitor of inos than cnos, in an animal model of ss. method: in anesthetized rats, catheters were placed in the femoral vein and artery. rats were given an iv bolus of lipopolysaccharide (lps, mg/kg), at baseline (to). after h (t ), rats received at random an infusion of either can ( mg/kg/h; can group, n=l ) or an equivalent volume of . % naci ( cc/kg/h; nac group, n= ), giyen over h (t -t ). a third group (sham group, n= ) received . % nac in place of lps, and then was treated like the nac group. mean blood pressure (mbp), blood lactate and nitrates (no ) were measured each h. glucose, creatinine and asat were also measured in rats (n= in each group). the can _+ * + "t . + . "~ . +_ . "t + " + " *p< . can vs naci ?p< . vs sham can suppressed the hypotension, reduced the hypoglycemia and hyperlactatemia, and attenuated the biological signs of renal and hepatic dysfunction induced by endotoxemia. these effects were associated with a lesser elevation of blood no , confirming a partial inhibition of inos. conclusion: l-canavanine attenuates the hemodynamic and metabolic consequences of endotoxemia in the rat. these effects may be related to a partial inhibition of inos. they contrast with the deleterious effects described with non selective inhibitors of nos. l-canavanine could become a new tool for the treatment of septic shock. rocalc tonin :marker of sepsis, ii~flammaiiur% t~ boifi .cheval*~ jf.timsit*, m.assicot**, b.misset*,/.carlet*, c.bohuon** saint joseph heap, paris**biochemistry institut g roussy, villejuif, ce bi~)l~i~ttectives_: high serum levels of procalcitoaln (proct) have been shown to be ~ss-ocinted with bacterial infection. however, few data exist about the ability of proct to differenciate septic shock and shock from other origin in which an activation of intlmmamtory mediators has been also demonstrated. methods: thirteen patients with bacterial septic shock (ss), patients with non septic shock (nss), patients with bacterial infection without shock ( nf) and icu patients without shock and without infection (control) were compared for proct levels at dayl, , , , . patients were classified blindly and independently fi'om proct results. twelve patients were excluded because any classification was impossible due to mixed pathology. proct was measured with ebemoluminescenee (brahms diagnostica-berlin). results: dayl, proct levels are significantly different between the four groups. dayl proct levels are correlated with saps (p= . ), infection ( . +_ vs _+ ,p= . ), shock ( _+ vs +.- ,p= . ), death at day ( _+ vs _+ ,p= . ). when shock and infection are introduced in multifactor &nov& only infection remains correlated with day proct levels ( = . ) in patients with shock, dayl proct levels are correlated with saps, infection and death at day , but not with arterial lactate levels (p= . ), white blood calls (p= . ) or fever (p= . ). proct levels remain higher i~i septic shock patients at day , and ( figure) . i c edpsion: procalcitonin levels in the first three days of shock are differen[" between septic and non septic shock patients. in patients with diseases known to induce acute an inflammatory process, procaldtonin seems to be a marker o~ infection. obiectives-to evaluate the effect of endotoxic shock on the distribution of blood flow between the mucosal and the muscular layer of the intestinal wall. methods: in fasted pigs, mean aortic pressure (map, mm hg), cardiac output (co, ml/min-kg),superior mesenteric artery flow (q sma, ml/min.kg), and phi, where measured before (control) and after i.v. endotoxin ( gg/kg). the blood flow to the mucosal and the muscular layer was measured in regions (proximal jejunum (pj), mid-small intestine (mi) and terminal ileum (ti)) by colored microspheres, using adjacent samples in each region. the muscular layer was separated from the mucosa by blunt dissection, and the flow determined independently in each layer. results: endotoxin with fluid resuscitation induced the expected decrease in map ( . _+ . vs . -+ . , p< . ), and phi ( . !-_ . vs . _+ . , p< . ), with a constant co ( _+ vs _+ , p= . ) and qst, aa ( . _+ . vs . _+ . , p= . ). the results of regional pertusion are presented in the table. (flow in ml/rain g of tissue; mean _+ sem ; * p< . vs control by two-way anova) conclusions-these data indicate that the mucosal flow increased during septic shock. they suggest that a decrease in phi may be due to hypoper~usion of the muscular layer or to metabolic alterations within the mucosa, despite a % increase in flow. acute increase in wbc count (from a mean of lo.oo mm a to o /mm~), between the rd and the th day of therapy. there was a decline of the wbc count to an average of about . mm a after decreasing the daily dose of the medication to mcg there was no increase in tile absolute number of the eosinophils during the whole course of the medication. there was a slight decrease in the c complement between . to . g/i. normal values . to . g/i there was no change in c values. conclusions : an early increase in wbc count was observed ( rd day) without subsequent increase in the number of immature types from bone marrow, probably due to the mobilization of wbc from the periphery and this increase was dose dependent. there was a slight decrease in c fraction of complement, probably due to the consumption of this fraction in the process of opsonization. no adverse effects of the medication were observed, during the treatment with the above dose. these data sugest that cm csf may be a useful complement to tile main antimlcrobial treat,nent ~ of septic [cu patients. objectives: as part of a large multicentric, placebo-controlled, randomized clinical trial investigating the effects of interleukin- receptor antagonist (ii-lra) in the treatment of severe sepsis and septic shock, this substudy evaluated in dem.il the acute hemodynamic effects of ii-lra in patients who were invasively monitored. methods: in a total of evaluable patients in whom vasoactive support was little altered, hemodynamic measurements were performed at baseline (twice), and i hour, h, h, h, h, and h after the administration of mg/kg (n= ) or mg/kg (n= ) of i - ra or the corresponding placebo (n = ). / patients ( %) were treated with adrenergie agents and / ( %) with mechanical ventilation. data were analyzed by a kruskal-wallis test. results: during the study, there was no significant difference with time or between groups in arterial pressure, cardiac filling pressures, cardiac index or left ventricular stroke work (figure). burmester, "~ man and h. djonlagic medical university (internal medicine, "cardiology, *'microbiology) and "**southern city hospital, lfibeck, germany obiectives: evaluation of the incidence of bacteremia and sepsis in patients with nontyphoidal salmonella (s.) infections, specification of risk factors, need of icu treatment, clinical course, and mortality in the group of the patients who developed septic complications. methods: data of all patients with microbiologically proven s. infections hospitalized in the medical university of lobeck and in the southern city hospital of l beck from to . results: within the observation period s. was isolated from the stool cultures of patients. in patients (g m, f, median age yrs) s. could be detected in blood cultures ( s. enteritidis, s. typhimurium). in addition, in of these patients s. was also isolated from other specimens (urine, liquor, and tissue fluids derived from abscess punctures). in all patients with positive blood cultures the clinical course of s, infection was complicated: ? patients developed mof (acute renal failure, ards, hemodynamic instability, dic) and required icu treatment for at least up to days, of the patients died. the predisposing disorders in the patients with s. bacteremia were (n=): aids ( ), immunosuppressive drugs ( ), chronic alcoholism ( ), malignancies ( ), none ( ). septic complications in patients with nontyphoidal s, infections are relatively rare (in this study < % of all hospitalized patients with microbiologically proven salmonellosis) but severe (mortality of approx. %). patients at risk for a complicated clinical course are predominantly those with predisposing disorders but occasionally also patients without evidence for an underlying disease. age (yr) + + death (n) duration of shock (h) + + noradrenaline (rag/h) , _+ + temperature (~ , + , + pvr (dynxsecxcm - ) + + co (ljmin) , _+ , , + , lactate (mmol/l) + , , + interleukin- (pg/ml) _+ + interleukin- (pg/ml) , _+ , , + , tnf-alpha (pg/ml) , + , + neopterin (nmol/l) , + , + crp (rag/l) _+ +_ pro-ct (ng/ml) , + , , + there was no positive correlation between serum lactate levels, degree of shock, hypoxemia and pro-ct positivity. pts with septic shock of bacterial origin entirely developed hyperprocalcitoninemia, whereas pts with cardiogenic shock, who expired within h did not. however, in late cardiogenic shock (> h) all pts developed fever of unknown origin and consecutive hyperprocalcitoninemia. these data suggest bacterial inflammation and/or mucosal translocation of bacterial products in pts with prolonged cardiogenic shock. the use of a loading dose of quinine ( . mg/kg base in h) is recommended in previously untreated patients (pts) with sfm, particularly in multi-drug resistance areas. this protocol is difficult to validate, since the viability of microorganisms is not assessed routinely in parasitology laboratories. objectives: to examine the evolution of parasite viability during the early phase of therapy of sfm. methods: from / to / , pts with sfm (who ) treated with iv quinine for less than h were included prospectively. blood samples were collected at o, , , , , and h viability was assessed by culturing parasitized red blood cells in the presence of h-hypoxanthine, and radioactivity was determined at h by scintillation counting. viability was expressed as the percentage of radioactivity compared to the initial sample. plasma quinine was determined by liquid chromatography. tile ratio plasma quinine (pmol/ )xlo /icso for quinine (nmo]/]) was called the parasiticida/ index. results: pts were included, • saps . -+ . . the initial parasitemia was t. + . %. complications of malaria were coma ( pts), shock ( pts), renal failure ( pts) and acute lung injury ( pts). all strains were sensitive to quinine (icso -- nmol/ ). in pts who were not given a loading dose, parasite viability increased by and %, with concomitantly low quinine levels ( and #mow] at h); pt died. in pts that received a loading dose (serum quinine at h = . -- . ~mol/]) a marked decrease of parasite viability (by +_ % at h) was shown. viability was inversely correlated with plasma quinine (r=. , p-.o ) and parasiticidal index (r=. , p-.o ). conclusions: even with fully sensitive strains, the use of a loading dose of quinine seems warranted in severe falciparum malaria in order to reach rapidly adequate plasma quinine ]evels, necessary to inhibit significantly parasite viability. l nkka, e ruokonell j takala. critical care research program, department of intensive care, kuopio univ hospital, finland objective: to determine the incidence of positive blood cultures, their microbial subgroups and to evaluate the outcome of icu patients with different bacleremias. material and methods: we analysed all positive blood cultures in consecutive admission to a university hospital icu in - and the icu and hospital survival of the bacteremia patients. during these years patients had positive blood cultures that were considered as clinically relevant, excluding colonizations or contanfinations. results: patients with positive blood cultures had an icu survival of . % (vs. , % in all icu patients) and six month survival of . % (vs. . % in all icu patients). the most common bacteria were enterobacteriaceae ( , %), staphylococcus aureus ( , %) , coagulase negative staphylococci ( . %), pseudomonas ( . %) and slieptococci ( . %). obiectives: to evaluate prognostic factors and mortality in consecutive patients (pts) with hiv infection and septic shock. methods: from - to - , records of consecutivepts with septic shock (crit care med , : - ) admitted to the icu were reviewed retrospectively. results: among pts with septic shock admitted during the study period, had hiv infection- of whom had aids-(gr. i) and were hiv-negative (gr. ill. ten gr. ii pts ( %) were irnmunosuppressed because of neoplastic or immune dlsease. mechanica] ventilation was required in % gr. i and % gr. ii pts in gr . i pts ( %) a multivariate analysis demonstrated that hiv infection and sap i were independently predictive of death in pts with septic shock. ~onclusions: evidence of increased mortality, number of organ failures and higher severity scores (saps i does not take into account immunosuppression) is demonstrated in hi v-positive pts, infection with hiv appears to be an independent prognostic factor in pts with septic shock. the frequency of opportunistic infections (often responsible for delayed diagnosis and treatment) may contribute to the poor prognosis in this population. obiectives: to determine interleukin (il)-i levels in plasma of patients with sepsis and septic shock. to analyze the relationship between plasma il- and the proinflammatory mediators, tumor necrosis factor-aifa (tnf) and il- , the underlying severity of the disease and the evolution of patients with sepsis. methods: we studied critically ill patients ( men, women; - years old) in three diferents groups. group i: patients without evidence of infection, group i : patients with sepsis and with septic shock (group iii). we measured plasma il-lo, tnf and il- levels in the first hours of diagnosis. severity of illness was estimated with the acute physiology and chronic health evaluation (apache ii) scoring sytem. results: plasma levels of il- were higher in group iii (median, pg/ml; range, - pg/ml) than in group ii (median, pg/ml; range, - pg/ml; p <. ) and group i (median, pg/ml; range, - pg/ml; p <. ). median il- concentrations did not differ among patients who survived (median pg/ml; range, - pg/ml) and those who died during the overall follow-up period ( days) (median, ; range, - pg/ml); but patients who died in short-term (< hours) with catecholamine-refractory hypotension showed the highest concentrations of il-io (median, pg/ml; range, - pg/ml). in patients with bacteriemia ( %), levels of il- were higher (median, pg/ml; range, - pg/ml) than in those with negative blood culture (median, , pg/ml; range - . pg/ml; p< . ). there was a good correlation between plasma il-io concentration and levels of tnf (r= . ; p < . ) and il- (r= . ; p < . ). the correlation between levels of il- and the apache ii score was significant only in the septic shock group (r= . ; p <. ). conclusions: in septic shock, il-io and proinflammatory citokines are released in high concentrations. the significant correlation observed in patients with septic shock between il- levels and apache ii, short-term death and bacteriemia can possibly be explained by the massive inflammatory response in septic shock with fulminant course. intensive care department -calmette hospital - lille -france. in septic shock, inadequate splanchnic blood flow may play a prominent role in the pathogenesis of multiple organ failure. measurement of gastric phi has been propose to evaluate tissue oxygenation in splanchnic organs. objectives: to compare gastric phi values with hepatic icg clearance, an index of liver blood flow and function ; to determine if one of these two methods could be proposed to assess the entire splanctmic peffusion in septic shock. methods : patients (age : • years ; saps ii : • were prospectively investigated (septic shock : bone criteria). following parameters were collected during hours : systemic hemodynamic parameters (swan ganz catheter a h -ref computer -baxter lab.), calculated systemic oxygen transport (do ), oxygen consumption (vo ) by indirect calorimetry (deltatrac datex lab.), gastric intramucosal pco (pco ss) and phi (trip -ngs catheter -tonometrics lab.) and plasma disappearance rate of icg (pdr dye) (femoral artery fiberoptic/thermistor catheter , cold z computer -pulsian medizintechnik, germany). correlations were performed using a linear regression. elevated in all days with the highest value in second and third days of treatment. nonsurvivors had higher values of these parameters than survivors but differences did not reach statistical significance. another trend of changes were observed in selectin p (gmp- ) concentration. in all patients concentrations measured were elevated but in survivors after not significant decrease this parameter in second day another one had simmilar values. in patients who died we noted significant decrease in third day (p < . ) whereafter prominent increase, significant after seventh day, in comparison to third day value and value in survivors group. icam- concentrations in all patients reached high levels and in nonsurvivors after four day of treatment significant increase in comparison to survivors we found. conclusions: multiple trauma complicated with sepsis induce rapid elevation of concentrations of il- , il- and increased expressior of adhession molecules (selectin e, p, icam- ) measure of icam- and selectin p concentration determine lung injury severity and prognosis as to health and life. (clp) .pathophysiology of cip is unclear, but changes in regional bloodflow may be a ~ignificant factor. nerve blood flow (nbf)is reduced in rat models of hemorrhagic shock (g),but no information is available in sepsis. we studied the comparative effect of acute endotoxemic shock {etx)& h on perfusion of rat sciatic nerve. methods: male sprague-dawley rats were anesthetized with pentobarbital (ip), instrumented with a tracheostomy, carotid arterial & venous catheters and mechanically ventilated (fi = . ). the left sciatic nerve was surgically exposed. monitored variables included: a) mean arterial pressure (map,mmhg) ,b) nbf (ml/ o g/min) by laser doppler flow meter,c) nerve internal arterial diameter (id ~ m) by video image shearing and splitting method. after stable baseline measurements were obtained, acute hypotension was induced by randomly assigning the rats to etx ( . b , difco) in saline at mg/kg or h. both interventions produced % reduction in map within min., which recovered to baseline values spontaneously in etx group, & by reinfusion of heparinized withdrawn blood in m. data were analyzed by linear regression, two-way repeated measures analysis of variance followed by bonferroni-t method. experimental stages were:( )baseline, ( ) mid-point of map reduction; ( ) nadir of hypotension, ( )midpoint of map recovery, & ( ) after stable recovery of map. both etx & h induced shock result in similar reduction in nbf consistent with lack of autoregulation in peripheral nerve vessels independent of etiology. since cip is primarily associated with sepsis, it is not likely that acute reduction in nbf alone causes cip. direct & indirect neurotoxic effects of mediators of sepsis need to be evaluated. .':_.~::::o o:oc ., objectives : evaluate the relationship between il- , a cytokine which inhibits tnf, production and protects mice from endotoxin toxicity, and the other proinflammatory cylokines, tnf~, il and ils in severe sepsis and septic shock. methods : twenty-eight icu patients ( m, f, mean age + y) were studied as soon as they developped a severe sepsis (n = ) or a septic shock episode (n= ) as defined by a conference consensus in ( ). tnf~, il , il s and il- plasma levels were measured by immuno-radiometrie assays from medgenix (fleurus, belgium). lc mean and range. results : the comparisons between cytokine levels in severe sepsis versus septic shock were made using the logarithm of the value in order to normalize the distribution of data, and student test. il- plasma levels were higher in patients with septic shock than in patients in severe sepsis. there was a significant correlation (p < . ) between il- and tnf a (r= . ), il- and il~ (r = . ) and il- and il s (r = . ) as well as between il- and apache n score (r= . ). patients who died (n = ) had il- levels higher than patients who survived but this difference was not statistically significant ( pg/ml vs . pg/ml; p> . ). conclusions : during severe sepsis and sepsis shock, il- seems at least to follow the same evolution (increase in plasmatic level) with the severity of sepsis as the other cytokines. reference : ( ) crit care med ; : - . objectives: to evaluate the effects of steroids on hemodynamics and mortality in septic patients with konwn levels of cortisol concentration. methods: retrospectively we analyzed data ofpatients with documented septic shock who received steroids after assessment of adrenal function. in all patients hemodynamic parameters as well as the necessary vasoactive medication were assessed, before and hours after corticosteroid medication. immediately before administration of corticosteroids adrenal function was evaluated with cortisol levels before and after synthetic corticotropin ( . mg). finally we studied mortality. we defined a positive respons on corticosteroids as an elevation of map of at least mmhg and/or a decrease in the necessary vasoactive medication of at least % within hours. adrenal insufficiency was defined as a cortisol level after stimulation of less than nmol/l. results: of patients were found to respond to steroid medication, did not. mean cortisol levels before and after corticotropin were • and • nmol/l in the responder group (rg) and • and • nmol/l in the non responder group (nrg). in the rg out of ( %) were found to have an adrenal insufficiency, in the nrg out of ( %). in the rg -weeks mortality was . % (l out of ), the overall mortality % ( out of ). mortality in the nrg was % ( out of ) (p < . ) and % ( out of ) (p < . ) respectively. conclusions: in patients in septic shock there is a beneficial effect of steroids in case of adrenal insufficiency, but also in a subgroup with normal adrenal f{unction. obiectives: intercellular adhesion is a critical step in the accumulation of leukocytes. postischemic cardiac lymph has the capacity to stimulate icam-i. in the coronary microcirculation neutrophils can be trapped and in many cases obstruct capillaries, previously we found that troponin t (s-tnt) a marker for myocardial iechemia, was increased in septic patients. the aim of the study was to follow slcam- and s-tnt levels continuously starting at the beginning of sepsis. methods: patients were ingluded in this institutionally approved study after relatives had given their informed consent. all patients were included within hrs following the beginning of sepsis. blood was drawn every hrs in the first ;~ hrs, after hrs, followed once per day for days. s-tnt, icam- , elam (elisa's, boehringer mannheim inc, r&d systems ltd.) arterial and venous blood gases were determined, an ecg and a complete hemedynamir measurement including cardiac output were obtained. all patients received adequate volume and catecholamine therapy (norepinephrine, dopamine, dobutamine; median (range) . ( . - . ), . ( . - ), . ( . - . ) pg/kg/min, respectively). statistical analysis: wileoxon signed rank-sum test. . ( . - . ) . patients had s-tnt levels > . pg/l. of these died, whereas only of patients died with s-tnt values < . pg/l (p= . ). all patients that died had elevated sjcam- levels ( ilg/l:cut-off ) whereas in the survivor group only % had elevated icam- levels (p= , ). conclusions: increased slcam- and s-tnt levels were found during early sepsis in the majority of patients, a high sicam- and s-tnt value was associated with a higher mortality. the research of the noninvasive haemodynamic monitoring accelerated recently all over the world. the aim of our study was to test whether the changes of the haemodynamk parameters measured by impedance cardiography (icg) were corresponded to clinical changes in septic patients. investigations were performed on critically ill postoperative septic patients (their multiple organ failure score was - /with icg monitor. in cases the investigation~ were performed in septic shock. the measured parameters were: heart rate (hr), mean arterial pressure (map), cardiac output (co), peripherial resistance (svr),preejection period (pep), and ventricular ejection time (vet). these parameters were measured during - hours in every minutes, depending on the patients cl~tnical condition. results: at the septic patients the hr and the co ]~reased. in septic shock the co was significantly higher the svr lower than in the septic group. in the hr there was no difference between the two groups. in septic shock noradrenalin influenced more effectively the measured parameters than dobutamin. conclusion: the trend of the measured icg parameters correlated with the clinical changes of septic patient's state. the noninvasive haemodynamic monitoring by impedance cardiography helps the planning and leading the adequate intensive therapy of these critically ill septic patients. to evaluate the development of sirs, sepsis and septic shock in hospitalized patients with fever, a prospective study was performed on patients using previously defined criteria. methods: normotensive patients with fever (temperature > . ~ axillary), admitted to the department of internal medicine were evaluated for the existence of sirs during the first three days of the study and sepsis at inclusion. during a follow-up period of days the patients were daily evaluated for the development of sepsis or septic shock. results: most patients ( %) had or developed sirs within the first three days, patients ( %) did not. sepsis was present in % at inclusion. in patients with sirs, % did not progress to sepsis or septic shock, % progressed to sepsis (mean interval . • . days), and patient (< %) directly progressed from sirs to septic shock. in patients with sepsis, % progressed to septic shock (mean interval . • . days). sepsis was preceded by sirs in %. septic shock was preceded by sepsis in % and by sirs in %. conclusions: % of patients with fever in an internal medicine department develop sirs, or sepsis. furthermore, progression from sirs to sepsis or septic shock is poorly predicted by fever or sirs. nevertheless, all patients with septic shock were preceded bysirs or sepsis. taken together, this may indicate a severity hierarchy of the syndromes. however, fever, sirs and sepsis are relatively poor indicators of development of septic shock. this supports further research on additional predictors of septic shock. b. m.manuylov, v.b.skobelsky (moscow) in recent years sodium hypochlorite (sh) has been successfully used to eliminate pyo-septic complications. moreover, the mechanism of the sh effect on the immune system has not been sufficiently studied. the aim of the present investigation was to study the mechanism of sh effect in inflammatory pulmonary diseases. patients with double pneumonia were subjected to the evaluation. sh in the concentration of mg/l in the volume of - m / hours was administered by drop infusion into the central vein. to evaluate one of the defence systems the leukocytes activity by the chemoluminescence technique was studied. in all the patients baseline secondary immunodeficiency which was indicated by the decrease in the luminescence level was established. even hour after the sh administration the leukocytes activation exp-ressed by the enhancement of their chemoluminescence . - times was observed. this supports the available findings that accumulation and liberation of the oxygen active forms (ol'oh, ' , h ) are accompanied by the increased phagocytosis, i,e. the signs of "the oxydation explosion" testify to the favourable sh effect on the course of inflammation processes. the use of sh permitted to decrease the percentage of lethality in double pneumonia by % in the intensive care unit over the year. at the same time, excessive activation of free radical oxygen may be a damaging factor. therefore, precise individual control over the choice of concentration, dosage and the preparation administration rate is required. prospective, double-blind, placebo-controlled, trial of atiii substitution in sepsis r. a. balk objective: pilot study to evaluate the efficacy and safety of atiii substimtion therapy in patients with sepsis. efficacy assessed using change in mortality or organ failure/dysfunction. adult patients meeting a definition of sepsis and cared for in a tertiary care academic medical center in chicago were identified and prospectively randomied to receive either atiii (kybernin p) or placebo in a double-blind treatment protocol. all other therapy and patient management were under the direction of the patient's attending physician. all patient's were followed for days and the organ dysfunction/failure were scored using published scoring systems (jordan et al crit. care med. , goris et al arch. surg. , kuaus et al ann. surg. colldusions:wha~ we met the shomaeker objectiv% the mortality and the pro~os[s were i~ttc*. those criteria were obtained with file tradititmal t~ctor likr doht~mme, hut c.~vh ~,as ca in~aertam measure. they ac~s smxergically in the optimizatic~l of the fell vmtrictdar work index, tad fimdameatally cavh seox~s to have an impo.aat role in the better respiratory ev-altmtioa, leaving yet the possibility to coltrol the flui& r althou~l eomproved it's not aec~pt~xl file importmlce h* the diminution, of the sepsis modiat~lrs llke fnt and il- with h~wmotiltrafi(al, stopphlg the evolution to nmltiorganic failure mid de~easethe mortality. with ours clhlicals results, we could saythat cavii in multiol~atlie disfut~oa septic patieats, se~r~ to be an c xilna] supoa or troatmeat maesure. of anaesthesia and intensive therapy, medical university of prcs, p~csf hungary. objectives: since some biological effects of bacterial endotoxin require an interaction between the lps molecule and a serum factor(s), we hypothesized that lps-induced no production and cgmp accumulation in vascular smooth muscle cells (vsmc), a mechanism ~thought to underlie cardiovascular collapse associated with septic shock, is modulated by serum factor(s). methods: cultured vsmc from rat aorta were challenged with e. coli lps for - hours either in the presence or absence of fetal calf serum (fbs), and no production was monitored by radioimmunoassay determination of cgmp content of hci extracts. results: in the absence of serum, o ng/ml lps was required to increase cgmp levels, whereas the presence of % fbs shifted the lps concentration curve i times to the left. similarly to fbs, human serum also potentiated lps-induced cgmp accumulation. in contrast to lps, serum had no effect on cgmp accumulation elicited by sodium nitroprusside, a no releasing agent, suggesting that the sensitivity of vsmc to generate cgmp in response to exogenous no is not modulated by serum. heat inactivation (> ~ min) but not removal of small molecules (< , d) from the serum by dialysis, reduced the potentiation of cgmp accumulation by serum. time course studied indicated that serum is required within the first min of lps exposure to increase cgmp levels. to investigate whether the effect of serum is specific for lps, we treated the cells with increasing concentration of interleukin -~ (il-i). % fbs shifted the il-iinduced cgmp responses five times to the left. conclusions: our study suggests that lower concentrations of e. cell lps and il-i require a heat labile macromolecule in the serum in order to elicit no production. this factor is present in the human serum and it may play a potentially important role during no synthesis induction in vsmc. objective: to evaluate the factors of acquisition and the outcome of methicillin resistant staphylococcus aureus (mrsa) bacteremia in an intensive care unit (icu). methods: all patients in which bacterermia due to staphylococcus aureus developed > hours following admission to our icu, during a year period ( january through january ) were reviewed. patients (pts) were included, mean age , y (sd , ), saps , (sd , ), mac cabe ( and ) %, mortality directly due to sepsis %. pts had mrsa bacteremia and methicillin susceptible staph. aureus (mssa) . both groups were compared using the chi square (with correction of yates), fisher's exact, student's t or wilcoxon test. results: there was no statistically significant difference between mrssa and mssa regarding at age ( , + , vs , + , ) , saps ( , + , vs , + , ), use of vancomycin ( % vs %), mechanical ventilation ( % vs %), number of days (d) before the drawing of the first positive blood culture (median d, range - d vs median d, range - d). more mrsa than mssa pts had previous use of nonsteroidal anti-inflammatory drugs (nsaid) ( % vs % p< , ), central venous catheter infection due to staph.aureus ( , % vs % p< , ), but previous use of antibiotics was not significantly different ( , % vs %). the outcome of the bacteremic pts was not statistically different: saps at the first day of bacteremia ( , +_. , vs , + , ), severe sepsis and septic shock ( % vs %), persistence of the bacteremia ( % vs %), mortality directly due to bacteremia ( % vs %). conclusion: previous use of nsaid, infection of venous central catheter are more frequently associated with mrsa bacteremia. thus, similar to others studies (hershow infect control hosp epidemio ; : - ) , these results do not indicate that mrsa is associated with increased virulence. objectives: to closer definition of mosf formation mechanismes in nosocomial sepsis (ns) the complex clinicobiochemical, microbiological, immunological, functional exaroination of cases with ns had been done. methods: examination of cellular and humoral immunity, nonspecific immunologic reactivity, systemic and hepatic circulation, microbiological examination of blood,electro-and echocardiography, sonography and computer tomography of chest and abdomen organs were obligatory. autopsy findings of dead cases had been analized. results: in cases ( , %) opportunistic pathogen microscopic flora ( staphylococcus anreus,staphylococcus epidermidis, staphylococcus saprophyticus) had been found out in blood inoculations. in cases ( %) side by side with destructive process in lungs the bacterial endo-and myocarditis with blood circulation failure had been determined.in cases ( %) simultanious lesion of three organs (heart,lungs,liver) had been found. morphologic examinations of dead cases ( %) internal revealed involvement of them in mosf-syndrome.hyperplasia of adenohypophysis;sclerosis of adrenal glands cortical layer;perivascular brain oedema,paralysis of brain capillaries and plasmorrhagia, cerebral thrombosis and cerebral abscess,necrobiosis of epithelium tubules of the kidney,pletora of hepar, fatty and granular degeneration of hepatocytes had been found.atrophy of white pulp and hyperplasia of red pulp, supress of lymphoid tissue, plethora and formation of infarctious had been found in spleen. mentioned changes in spleen were indispensable in ns. conclusion: in ns spleen can not secure it functions to support and appropriate detoxication potencial of organism,elimination of microbes,toxines,antoallergenes. insolvency of immunological link of antimicrobic defence is the starting mechanism of mosf developmentin ns. %neviere, jl. chagnon, b. vallet, d. mathieu, n lebleu, f. wattel ] ept of intensive care, hop calmette, lille, france ~everal studies have described tiypoperfusion of intestine during sepsis. owever, it is unknow whether the mesenteric blood flow is associated with nucosal hypoperfusion. additionally, the effects of resuscitation on the ntestinal microcirculation remain controversial. bjectives : to describe the effects of endotoxin in a porcine model during ~hock and resuscitation. ~ethods : ten pigs ( kg) were anesthetized and instrumented for "neasurement of cardiovascular variables. gastric and gut oxygenation vere assessed by intra-mucosal ph and microvascular laser doppler lowmetry. after baseline data collection, a minute intravenous infusion )f escherichia colt (serotype h , sigma, st. louis, mo) was begun ~t a rate of pg/kg. an infusion of either saline at . ml/kg/min (group ; n= ) or saline and dobutamine at a rate of pg/kg/min (group ii; n= ) vas begun mn after the end of the endotoxin infusion. tesults : to td t ~ fl w fluid ioadin,q alone sfyras d, k perreas, e douzinas, k spanou, m pitaridis and c roussos critical care dpt, evangelismos hosp., athens univ, school of medicine. obiectives: much controversy exists concerning the beneficial effects of cvvh on sepsis. we studied the effects of cvvh application on septic patients with reference to the following parameters: i) survival rate ii) cytokines' removal and iii) timing of cwh onset. methods: patients with sepsis (criteria according to accp/sccm, ) underwent cvvh as soon as they developed renal failure or dysfunction (urinary output< ml/ h, cr> . mg/dl and bun> mgd'dl ). specimens were collected: blood samples before cvvh and therafter both blood and ultrafiltrate (uf) samples on , and hours. cytokines tnfa, i - and ii- were measured by the immunoassay method in all specimens (uf and plasma -p) and sieving coefficient ([uf]/[p]) and h solute mass transfer of tnf and i - were calculated (v h x [uf] ). the apache ii score before cvvh onset, the duration of icu stay and the timing of cwh application related to the sepsis onset in days (ta) were recorded.with respect the mortality two groups were formed, i.e. group a (survivors) and group b (non-survivors) . the morbidity period in days of those septic patients who died in the past year and were not subjected to cwh (group c) was compared to that of group b. results: group a included pts and group b pts with mean+sd age ( _+ vs _+ , ns) and apache scores( _+ vs -+ . , ns). the mean ta-+ sd was . + vs -+ , p< . . the mean_+se morbidity period of group b vs group c was _+ vs _+ . p< . . the mean values of cytokines are presented in the following figures. the sieving coefficient for tnf was . and for i - was . . the solute mass tranfer was -fold the actual plasma content at a given time. . o conclusions: i) early application of cvvh seems to favourably affect the outcome of septic patients, ii) cytokine plasma levels do not decrease although cytokine removal is substantial, iii) it seems that cwh application in sepsis of any stage helps to buy time for further treatment. the most commonly monitored variables in shock stages idclude : arterial pressure, heart rate, central venous pressure, pulmonary artery wedge pressure and cardiac index. with vigorous therapy it is possible to bring these values back into the normal range in both survivors and nonsurvivors. therapeutic goal in septic shock stages is to maximize the values of cardiac index, delivery (do ) and consumption (c ). objectives: the main purpose of this article is to determine the relationship betwee~ delivery an consumption as a sign of hypoxia. fifteen patitents with septic shock were treated with intention to maximize the value of ci,d and v . we compared the levels of these parameters between the survivors and nonsurvivors and found no significant differences after hours. high levels of do and v may not guarantee against tissue hypoxia in early stage of septic shock. zjar~iic, dj janjic, lj. gvozdenovic, a.komareevic. t.petrovic, &marjanovic, institute of surgery, novi sad, yugoslavia objectives: evaluation and mutual comparison of clinical signs, laboratory data and microbiological monitoring in the patients with burn sepsis. method: retrospective analysis of the recorded data of all burn patients treated in our department between january and december . specially attentions were given to data considering wound infection, positive haemocultures, positive urinocultures and characteristics of septic state. results: out of patient there were ( , ~) adults and ( , ( ~) children. almost two thirds of the patients ( - , ~) were males. the predominantly cause ( , ~) of children's burns was scalding b~y hot liquids and flame burns ~ , ~) in adult patients. the most frequdntly species isolated from surface swat~ were pseudomonas aeruginosa ( " in adult patients) and staphyloccocus epidermidis ( , % in children). in only five patients ( , ~ the haenmcultures were positive -pseudomonas aeruginosa was isolated in three and staphyloccocus aureus in two patients. urine infection was diagnosed in , % of all patients. the treatment protocol included use of imipenem and polyvalent pseudomonas vaccine again~ pseudomonas aeruginosa and vancomycin and aminoglycosides against staphylococcus aureus. total mortality rate in this group of burned patients was , ~, but the mortality rate caused of sepsis was low (i %) . conclusions: early detection of any signs of wound infection and symptoms of septic state is a foundation for prevention and treatment of burn sepsis. the burn sepsis could be reliable detected by continuously monitoring the patient's status and by systematic microbacteriological monitoring of the burned patients. hyperdynamic vasoplegic septic shock p.f. laterre, p. goffette, j. roeseler, j.p, fauville, a. poncelet, p. lonneux, m.s. l~eynaert. dept. of intensive care, st. luc univ. hospital, brussels, belgium. splanchnic ischemia is described as a common feature of septic shock and could determine the development of msof. therapy such as noradrenaline (na) aiming at improving blood pressure is expected to worsen splanchnic ischemia by its vasoconstrictive effect and subsequent reduction in intestinal blood flow. ob[ective: evaluate the effect of na on splanchnic blood flow. material and method : in a patient admitted for variceal bleeding, ards and sepsis with positive blood culture, a fiberoptie catheter was positionned in the portal vein after recanalisation of its portosystemic stent shunt. blood pressure (bp-mmhg) , ci, svr, do (vigilance ~ baxter), v (indirect colorimetry), arterial, mixed venous and portal vein blood gases, phi were determined before (to) and during (t ) na infusion ( , to , hcg/kg/min.) . changes in splanchnic flow were assessed by changes in portal oxygen saturation (sp ) and arterio-portal oxygen saturation gradient (sao, -spoe laterre, ,lp. pedgrim, th. dugernier, v. delrue, ph. hantson, p. mahieu, m.s. reynaert. dept. of intensive care, st. luc univ. hospital, brussels, belgium. aim of the study : prospective determination of plasma levels of in patients with ss and their correlation with the type of microorganism and outcome. material and methods : in patients (pts) with ss and severe sepsis, plasma levels of tnfti, ill-b, il and il were determined every hours for days and on day after fulfilling the criteria of ss and severe sepsis. results : in pts, sepsis was caused by a gram (-) microorganism, in pts by a gram (+) and in pts no microorganism was identified. there were survivors ( %) (s) and non-survivors ( %) (ns) . cytokines profiles and levels were not different between gram (+) and gram (-) sepsis. ill-b levels were seldom elevated whatever the group studied. tnfot and il- were significantly higher in ns than in s ( objective: to evaluate the effects on the nitric oxide synthase inhibitor l-n~ hcl ( c ) on myocardial performance in human septic shock. method: septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; map< mmhg) or the requirement for a noradrenaline (na) infusion >_ .i ]tg/kg/min with a map _< mmhg. cardiovascular support was limited to na _+ dobutamine (db), c was administered for up to h at a fixed dose-rate of either , . , , or mg/kg/h iv. during c infusion, na was to be reduced and if possible withdrawn, whilst maintaining map above mmhg and the cardiac index (ci) as clinically appropriate. assessments were made at baseline (t = ); at i h from the start of treatment (t = ); and at the end of treatment (t = ) with c . conclusions: c can restore systemic vascular tone in patients with septic shock enabling na therapy to be reduced and/or removed. the ci tends to fall whilst lv performance is sustained over time. c is a novel vasoacfive agent for the treatment of septic shock, which is undergoing further clinical evaluation. laterre, f. thys, e. danse, j.p. pelgrim, e. florence, z roeseler, m.s. r eynaert. dept, of intensive care, st. luc univ, hospital, brussels, belgium. therapy aiming at improving blood pressure and cardiac index in septic shock (ss) might have deleterious effects on regional blood flow. objectives : compare the influence of volume loading (vl), dobutamine (dobu) and noradrenaline (na) on sushepatic oxygen saturation (shoe) and svoe-sho, gradient in treated ss. material and methods : in patients with ss, ci (thermodilution) , doe, svo,. sho,, svoe-sho e gradient and lactate (l) were determined before (to) and after (t ); vl, dobu and na. results: in patients with treated ss, tests were performed (vl n= ; dobu n= ; na n= method: septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; map< mmhg) or the requirement for a noradrenaline (na) infusion ~> . ~g/kg/min with a map _< mmhg. cardiovascular support was limited to na + dobutamine (db), c was administered for up to h at a fixed dose-rate of either i, . , , or mg/kg/h iv. during c infusion, na was to be reduced and if possible withdrawn, whilst maintaining map above mmhg and the cardiac index (ci) as clinically appropriate. assessments were made at baseline (t = ); at h from the start of treatment (t = ); and at the end of treatment (t - ) with c . conclusions: c is a novel vasoactive agent that can sustain map in patients with septic shock, enabling na support to he reduced and/or removed. there is a tendency for the ci to fall during treatment, which may be reflex in response to the increase in systemic vascular tone. c is a promising new therapy for septic shock, which will now be evaluated in a randomised, placebo-controlled safety and efficacy study. k. guntupalli objective: to evaluate the acute effects of the nitric oxide synthase inhibitor l-n~ hc ( c ) on selected indices of organ function in patients with septic shock. method: septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; map < mmhg) or the requirement for a noradrenaline (na) infusion --> . [xg/kg/ min with a map _< mmirlg. cardiovascular support was limited to na + dobutamine. c was given for up to h at a fixed dose-rate of either , . , , or mg/kg/h iv. during c infusion, na was to be reduced and if possible withdrawn, whilst maintaining map above mmhg and the cardiac index (ci) as clinically appropriate. indices of organ function were assessed at baseline (t = ); at the end of treatment (t = ); and h after treatment (t = ) with c . results. -median values (* assessment made at h or when c discontinued). conclusions: there was no appareut dose-dependent adverse effect on these indices of organ function either during or after exposure to c . the plmelet count tended to fall whilst creadnine appeared to increase over time in all dose cohorts. this novel and promising therapy for septic shock will now be evaluated in a randomised, placebo-controlled safety and efficacy sludy. pharmacokinetics of c in patients with septic shock preliminary results z. hussein, b. jordan, c. fook-sheung, k. guntupalli objective: to evaluate the pharmacokinetics of the nitric oxide synthase inhibitor l-n~ hc ( cg ) given by continuous infusion for h in patients with septic shock. method: septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; map < mmhg) or the requirement for a noradrenaline (na) infusion --> . ~tg/kg/min with a map _< mmhg. cardiovascular support was limited to na • dobutamine. c was administered for up to h at a fixed dose-rate of either , . , , or mg/kg/h iv. plasma was collected from each patient over a h period and analysed for c . pharmacokinetic parameters were derived from plasma concentration-time profiles using non-compartmental pharmacokinetic analysis. results: the (cm~ -maximum plasma concentration; auc -area under curve; cl -plasma clearance; v,, s -steady state volume of distribution; t'/ -plasma elimination halflife). conclusion: the pharmacokinetics of c in patients with septic shock are dose-independent at infusion rates up to . mg/kg/h. at higher rates, clearance of c decreases without any marked change in volume of distribution. c metabolism may be partially saturable at dose-rates above . mg/kg/h. obiectives: investigate the effect of the no synthase inhibitor, l-nt-methylarginine hc ( c ) on the haemodynamics and survival rate in a conscious mouse model of endotoxin shock. methods: female cd- mice ( - g) were instrumented under gaseous anaesthesia (isofluorane, %) and connected to a swivel tether system for continuous monitoring of blood pressure and drug administration. results: after h recovery, endotoxin administration (e. col• :b , - . mgkg - i.v.) elevated the plasma concentration of nitrite/nitrate (nox) and caused a progressive fall in mean arterial pressure (map) from + to + mmhg (n= , p< . ) at h, with a survival rate at h, h and h of %, % and % respectively. c administered as a h continuous infusion ( mgkg-th -t i.v., n= ), h after endotoxin, inhibited the elevation of plasma nox and attenuated the fall in map from + to + mmhg (n= ) at h, with an improved survival rate at h, h and h of %, % and % respectively. conclusions: this study suggests that overproduction of no is involved in the hypotension and mortality characteristic of septic shock. inhibition of no synthase using c represents a novel and promising treatment for septic shock. cultures of e.coli ( , %) and candida( , %) were olso received from autopsy material of children;p.aeruginosa,unspored anaerobes,proteus sp.,s.aureus,b.pneumonia were found in the few cases. in adults the spectrum of bacterioflora was mo~ re limited speaking about the number of species and cultures. in generalized forms of bacterial pyo-septic pathology a wider specific spectrum of causative agents was revealed usua fly with associations. e.coli and k.pneumonia played the leading role in children as well as in adults. in general,k.pneumonia ( , %cultures) and common e.coli( , %)prevailed according to the date of microbiological investigations of authopsy material in pyo-septfc pathology in . objectives: .in spite of all clinical exertion sepsis is still the reason for high clinica! lethality. this study is characterizing the group of patients which survived a septi~ shock. methods: during a period of months all surgical patients on icu were registrated prospectively, more than parameters for each of them were documented'daily in a paradox file. results (see table ): of patients fulfilled the criterion of a septic shock (r. bone, ) , of them died at the lth day, while the surviving group of patients stayed almost days at icu. obiectives: to compare the effects of and % pentastarch solutions to a human albumin solution on oxygen delivery (do ) in septic patients. methods: this stud}, included septic patients with fever (t > ~ tachycardia flqr > /rain), tachypnea (rr > /min) or mechanical ventilation, leukocytosis (wbc> /mm ) or leukopcnla (wbc< ()/mm ) and a clinical source of infection, who required a fluid challenge. in each patient the pulmonary arterial occlusion pressure (paop) was < mmhg. patients were randomized to receive ml of % albunun (n:i ), hydroxyethyl starch (hes -mw /d.s. . ) % (n: ) or t % (n=i ); patients were also treated with adrenergic agents. results cardiac index (c ) increased significantly only in % lies (table) hemoglobin (hb) decreased significantly at min in the same group. there was not significant change in oxygen delivery ( do ). baseline ci alb . :: . (l'min/m ) hes % . = . hes % . polyneuropathy of the critically ill (pci ) is a well recognized complication, acquired in the course of severe illness. we undertook a prospective study, to estimate the severity, extension and time of onset of pci in a selected group of patient with established septic shock ( bone's criteria ). all patients received inotropic circulatory support and were mechanically ventilated. none received relaxants or aminoglycosides. pci was diagnose<by clinical investigation and by emg, and repeated weekly ( axonal degeneration ). after days ( day = onset of septic shock ) in % of the patients pci was demonstrable. after days % of the patients had pci. there was a strong correlation between pci and other mof and between pci and encephalopathy ( eeg ). we conclude that i. pci is a common complication after septic shock. . pci develops early in the course of illness ( % after days ). . pci can be considered as a part of mof, suggesting a common pathogenesis. objectives: we addressed two questions: ) can serial measurements of vapco and avph also reflect the onset of tissue hypoxia during endotoxemia? ) are whole body changes in vapco and avph associated with parallel changes in regional circulation? methods: in anesthetized, mechanically ventilated dogs exhaled gases were sampled for determination of oxygen consumption (vo ). a catheter was positioned into the pericardial cavity to induce cardiac tamponade. ultrasonic flow probes were placed around superior mesenteric, left renal and left femoral arteries, and the corresponding veins were cannulated. group l served as control (n= ), group (n-- ) received mg/kg of endotoxin. thirty min later, tamponade was induced to gradually reduce do . results: systemic do crit was higher ( . _+ . vs . + . ml/kg.min, p < . ) and critical oxygen extraction ratio (o ererit) was lower ( . +_ . vs . +_ . %, p< . ) in the endotoxie than in the control group. meslenteric and femoral do crit were higher in the endotoxic than in the control group ( . _+ . vs . _+ . mlll g tissue.min and . _+ . vs . _+ . ml/min, respectively, both p< . ). regional o ercrit were lower in we endotoxic than in the control group (mesenteric: . _+ . vs .i_+ . %, renal: . + . vs . -+ . % and femorah . -+ . vs . _+ . %, all p< . ). vapco and avph followed a similar pattern in both groups, increasing slightly before do crit was reached, but dramatically wh,en do fell below do crit. in the presence like in the absence of endotoxin, systemic and regional do crit calculated from vo , from vapco , or from avph were similar; do crit was also significantly higher in the mesenteric and the femoral beds of the endotoxic than the control dogs. systemic and regional do crit could be calculated from the blood lactate levels only in the control group. conclusions: during an acute reduction in blood flow i) vapco and avph can reflect hypoxic threshold in the presence like in the absence of endotoxemia. ) alterations in organ oxygen extraction capabilities induced by endotoxin can be reflected by regional changes in vapco and avph. objectives: enhanced nitric oxide (no) release has been incriminated in the vasodilation and myocardial depression characterizing septic shock, but the administration of no blockers has yielded equivocal results. the present study explored the systemic and regional effects of a no donor linsidomine (sin-i) during endotoxic shock. methods: anesthetized dogs received endotoxin ( mg/kg iv), followed min later by a saline infusion to keep cardiac filling pressures constant. oxygen uptake (vo ) was derived from the expired gas analysis. regional blood flow was measured by an ultrasonic flowmeter (transonic). results: the control endotoxie group (n= ) maintained low arterial pressure and systemic vascular resistance. the dogs receiving a continuous infusion of , , ~ug/kg.min of sin- starting min following initial fluid resuscitation (each dose for h), had a higher cardiac index ( . -+ . vs . _+ . l/min.kg, p< . ) and lower systemic and pulmonary vascular resistance than the control group ( -+ vs -+ and -+ vs -+ dyne.sec/cm , respectively, both p< . ). arterial pressure and pulmonary artery pressure were not influenced. sin- significantly increased the mesenteric blood flow from -+ to + % of baseline levels and renal blood flow from -+ to -+ % (both p< . ) but did not influence femoral blood flow. the relative blood flow was increased in the mesenteric bed (at all doses), and reduced in the femoral bed (at highest dose). systemic oxygen delivery, vo , oxygen extraction and blood lactate levels had similar course in the two groups. conclusions: in fluid-resuscitated endotoxic shock dogs, the no donor sin- increased cardiac index without deleterious effects on arterial pressure, and increased splanchnic blood fl w. objectives: sepsis syndrome is associated with the release of a variety of inflammatory mediators, such as interleukins, tumor necrosis factor and platelet-activating factor (paf). administration of paf, a naturally occuring phospolipid, to laboratory animals has been demonstrated to resullt in pathological changes that closely resemble those found in sepsis. in addition, paf antagonists of various origins have been demonstrated to attenuate cardiovascular collaps and to protect against lethality in endotoxemia. in the present study the efficacy and safety of the paf-antagonist tcv- g was investigated in sepsis syndrome patients. in addition, the putative inflammatory parameters tumor necrosis factor (tnf), interleukin il) - il- , and soluble (s) e-selectin were measured in both tcv- and placebo treated patients. metho.~a randomized, double-biind, multi-center study was undertaken to compare the safety and efficacy of intravenously administered tcv versus placebo (takeda chemical industries ltd., osaka, japan). tcv- was used as add-on to conventional therapy in the treatment of patients with severe sepsis and septic shock ( . mg/kg body weight intravenously over hrs, twice a day for one week). day mortality was registered, as well as vital signs, laboratory parameters, hemodynamic parameters, apache ii score and mof score. plasma samples for the determination of inflammatory parameters were collected twice a day for one week. the study was approved by each institutional review board and written informed consent was obtained for each patient. results: a total of patients were included in the study. one patient had to be excluded as a result of protocol violation of the remaining patients patients were randomised to receive tcv- and to be treated with placebo. there were no significant differences between the treatment group with respect to age. gender, and apache i~ score on admission. however, admission levels of il- and il- , considered to reflect severity of disease, tended to be higher in tcv treated patients: . . vs . ng/ml for il- (p. ) and . vs . ng/ml for il- (p. ) in tcv- and placebo treated patients, respectively. a remarkable difference in survival, however not significant, was observed at day i.e. the end of tcv treatment (mortality: out of in the tcv group and out of patients in the placebo group). the inc;dence ui ~-,~verse events, 'n both treatment groups were comparable. plasma il- and plasma il- levels tended to decrease more rapidly in tcv treated patients compared to controls (p=. and p=. , for il- and /l- respectively) conclusions: tcv- is safe as add-on treatment in sepsis syndrome patients. the data presented indicate that tcv- may enhance survival of sepsis syndrome which will be assessed in a phase ill study. objective: oxidation of lipids by free oxygen radicals playes an important role in sepsis. an important source of oxygen radicals is the respiratory burst of phagocytic leukocytes, especially~ polymorphonuclear leukocytes. clinically the hallmark of sepsis is the capillary leak, which is mediated in part by oxyradicals. the adult respiratory distress syndrom (ands} represents the most studied capillary leak phenomenon in sepsis. methods: in ii patients (df,~m, aged - y.) with verified septicemia had been included in this study. beginning from day oxidisable lipidautoantibodies (club), ~opterin and crp were determined in the patients serum and compared against the apache ii score during the days - . patients, f and m died @u= ring their stay at the icu, of them in less than h~urs: after admission. at the begin surviving patients showed olab values between - %, non-survivors between - %, com= pared to neopterin values of - m~ol/l in survivors and - ~mol/l in non-survivors. apache ii score didn t show any difference. during the following days olab sbowed an in= crease in survivors, while in non-survivors olab stayed equal or showed a decrease. no difference between both groups was found in neopterin, crp and apache ii score. as result we conclude, tbat lipidperoxidation playes an important role during septicemia. olab as a marker of this process are predictive for the outcome of patients. obiectives : to evaluate the influence of cardiopulmonary bypass ongastrointestinal transit. meth~xls; gastrocoecal transit time (gtt) in consecutive children on day after uncomplicated open heart surgery was compared to gtt in children after closed heart thoracic surgery and to healthy controls. gtt was measured by hydrogen breath testing, using lactulose (o, g/kg in a % aequous solution) as nonabsorbable marker. exspiratory hydrogen content was measured using a electrochemical system (stimotron). patients in both groups had continuous infusion of morphine and midazolam and were comparable in respect to catecholamine dose. children with a history of toddler's diarrhoea and children with elevated central venous pressure were excluded. results: gastrocoecal transit was delayed in all patients after cpb, no transit was achieved within minutes in / . after closed heart surgery gtt was delayed (+- ) min vs. (+- ) compared to controls, but transit was achieved in all aptients within rain. mean dopamine dose was , mcg/kgmin after cpb and , meg after closed heart surgery.. conclusions: after uncomplicated cpb gastmcoecal transit is extremely delayed. the degree of delay is not explained neither by the use of analgetic and sedative drugs neither by the use of catecholamines. factors directly related to cpb (e.g. low flow perfusion, hypothe,mia) may be responsible. these findings are of limited clinical relevance in ancomplicated cases. in critically ill patients delayed enteral feeding may contribute to infectious complications. studies of therapentic measures to accelerate gastrointestinal transit therefore are warranted. neonatal ecmo -czech experience. nekvasil r., penkova z, vasek l., plier p., bobula a novotna e., pavlicek v., hnilicka m. nicu and ecmo center brno and dept. pediatric surge ', children's hospital brno, czech republic. introduction. in spite of the fact that neonatal ecmo has been gradually considered a standard method of solving uncontrollable respiratol t failure in newborns in most countries of the western europe, the introduction of this sophisticated method in countries of the former communist block meets a lot of problem. material methods. in the course of two years, only newborns, b.w. - g, were reffered to neonatal ecmo because of uncontrollable respiratow failure. at the admission the average values of oxygenation index were + , and aado , -+ , kpa. results. newborns ( %) died shortly alter" admission or during transport without possibity to further is newborns ( , %) were treated using high-frequency ventilation (hfo or hfjv), one for conspicuous airway resistance paradoxically with low-frequency ippb. all ventilated newborns survived. ecmo was applied in newborns ( , %) and of them survived the mortality rate of group mentioned was %. conclusion. the fact that in the czech republic ( mil. population with natality rate of about . newborns/year) only small part of patients was reffered to neonatal ecmo has a number of causes. the most important are: unacquaintance of prognostic and indication criteria at forwarding workplaces and the aversion of neonatologist to all new.therapeutic interventions. last but not least, a negative role is also played by current change of health service systems when, under the influence of health-service insurance companies a newborn in serious condition given only a standard intensive care in primary and secondary nicu is literally "the golden calf", and therefore these workplaces either do not send him or send him too iate ~o an ecmo center. stndy aim: urfactant, which is being applied into the lungs for treatment of respiratory distress syndrome, can reach the circulatory blood system by absorption. it refinances local fimctiun of macrophages and lymphocytes and increases the accumulation of nentrophils into the hmgs this eunld influence the local acute phase reactiml in the hmgs after surfactant application. "ilia aim of the stud), was to investigate the influence of oatural and artificial surfactaat onto the acute phase reaction and the blood elottiog system. material :and methods: a) measurement of tnf-a, - , ltb and thromboxane b release in whole blood: each of . ml hepariaised blood of healthy adult volunteers was iucubated lbr hears with eillier ill ug/ml lps, mg/ml b&,ine smfactant (alveulhct/themae), rag/nil artificial surfactant (exosurf/wellcome), og lps + i mg/ml bovine surfactant or i ug lps + i mghal artificial sorfactant, tleparinised bhx-,d without additions was used for controls. ' e concentration of e)lokines and eicosanoids ".van measured semiquantilatively by eijsa or eia (dimmva/hamburg) after ceatrifagalion, b) measurement of platelet aggregation: each of . ml haparinised hltxxl of healthy adult vohmteers was inculmled lbr hours with eilher aghnl i,ps, i mg/ml bovine surfactant (alveafact/thomae), i mg/ml artificial snrlhctant (exosurf/wellcotne), it} ug lps + i mghnl bovine snrfactant or ug lps + i mg/ml artificial surfaetant, tlepminised blood withont additions was nsed for controls. platelet aggregation in whole blood was measured by impedance in the aggregometer (g~nstaedt). c) measurement of the dotting activity: citrated bleed of healthy adult w~lunlccrs was mixed with difl'ereul couccalrations of imvine or artificial snrfactant fad then prolhrombiu tiaras and imrlial thrmnlx~plaslia filues were ineasnrcd. for measurement of the prokoagulatioo acfivily the reagent in the qnick test was replaced by surfaclant. results: dependmlt on the dose both surfactants stimulated the release of - but not or tnf-a io wlmle blood. "illere was no suppression of the lps-indaeed eytokine-release. both surfaclants did not directly influence the extrinsic blood coagulation system, while both activated the inniasie activity dependant on the dose. platelat aggregatiun was slightly stimulated by bovine snrfactunt and strongly inhibited by by artificial surthctant. in comhinafion with . ~ both factors showed no difft.'renca to lps ahme.'fhe reltu.tse of eiconasnid~." was stimolated more by artificial surfactant then by bovine surfilctant with regard to the cyehmxygelmse (thromboxsne b ) and the lipooxygenase (lencotrieae b ) pathways. conclusion: we cooclude: ) i:lovine as well as artificial surfaelant stimulate the cellular inmnn]e response. ) bovine as well as artificial surfnctant activate the intrinsic ctmgnlation cascade. ) bovine surlilctant stimulates platelet aggregation, artificial sar-fijctant inhibits platelet aggregation.. introduction: although the use of modem noninvasive methods like measurement of tope , tcpco or san leeds to an carly infonnation about pathologic alterations of the gas exdmage of ventilated patients, these methods cannot replace invasive bloodgas analysis. a new noninvasive method to monitor the capillary gas exchange is the reflection spectrophotometry. to record reflection spectra with a ldgh sensitivity on the surface of tissue we eonstnmted a special mierolightgnide photospectronmter (empito). this spectrometer enables the investigation of local helerogenities of llbo and lb content, capillary flow rate and oxygen uptake rate. aim of the study: ) to compare the sousitivity and specifity ofthe empilo with other non-invasive method~ of monitoring the gas exchange in neonatal intensive care patients. ) to investigate the possibility of obtainiug infonnations about the local nptake and the venous as well as arterial satnration. patients and methods:we investigaled non-selected patients of oar pediatric intensive care unit. for coulinnons monitoring we conslracted a special sappert to fix file end nf the microlightguide+ during the investigation tope , tcpco and san were measured by standard methods. "fo investigate the local tisslm oxygen uptake we recorded spectres within minutes by moving the lightgnide over an described area of the skin of the patient. 'lhe reselting i(gx) l ibo vahms were sorted by a software package. on the assumption that the low values correspond to the tibo value of the veaons ends of the capillaries and the high values to those of the arterial ends we ) it is possible to gel infonnations about the local o -uptake and arterial saturation ia the peripheral tissue by photoslg'ctroscopy. ) in combination with noninvasive pl i-measorement it seems possible to reduce withdrawal of blood for invasivn bhmd gas analysis. objectives:improve ventilation,tissue oxygenation and acid base balance among extremly low birth weightand premature infants. methods: fourteen cases were s~udied,their gestational age ranged from( - )ws.continnous positive air way pressure was applied to six cases at peep level from ( - )cm h o through nasal pronge,(group i),the other cases were managed as routine,(group ii).blood gases, tcpo ,tcco ,resp.rate,depth and pattern were monitored for assessment of tissue oxygenation and ventilation, results: our rasults showed that early application of cpap improve ventilation among ( . %)of cases,while ( . %)of cases need imv.the cases of group ii need imv among ( %)of the studied cases during the second or the third day of life. conclusions:-this preliminary study showed the import-............ ance of early application of cpap before the onset of respiratory distress syndrom to improve spontaneous ve ventilation,tissue oxygenation and to gecrease the risk of intubation. comparative assessment of pediatric intensive care; a national multicenfre siudy. reinoud j.b.j. gemkc, gouke j. bonsel , the dutch picasso (pediatric intensive care assessment of outcome) study group. twilbelmina children's hospital and utrecht university, utrecht department of clinical epidemiology, academic medical center, : amsterdam, the netherlands the performance of all ( ) pediatric intensive care units (icus) in the netherlands ( tertairy and non-tertiary) was analyzed in an open prospective muiticenter study. effectiveness of care was defined as the ratio of observed to prism-score derived expected mortality aenee, standardized mortality rate). efficiency was determined by objective criteria (mortality risk > % or administration of at least icu-dependent therapy)'. consecutive admissions aged < years old were included. overall, observed and expected mortality were in good agreement (p > . ). between hospitals, crude mortality showed wide variations (mean . %, range - %). however, in each center, observed and expected mortality were similar (mean ratio . , range . - . ). in tertiary care centres, severity of illness corrected mortality in high-risk patients was less than in non-tertiary care centres; paradoxically, in low-risk patients the opposite was found. probably the large proportion of low-risk tertiary care patients suffering from severe, incurable chronic disease, explains the higher mortality in this group. this indicates that simultaneous assessment of circumstances of dying and of long term morbidity in similar future studies is imperative. the average proportion of efficient icu days was %, however large variations between units were found (range: - %). in conclusion differences in mortality rates among pediatric icus were explained by differences in severity of illness. high efficiency rates in combination with adequate effectiveness, found in several centres suggest that admission and discharge decisions might be improved by a better selection of high risk patients requiring icu-dependent therapies, especially in less efficient centres. objectives: previously published studies showed that serum lactate levels correlated with outcome of severe ill adult, 'we hypothesized that critically ill newborns are often incurred hypopeffusion manifested by elevated lactate levels. these initial blood lactate levels should be related to nicu outcome. design: prospective study with ethical comfnittee approval. setting: the -bed neonatal intensive care unit of a university hospital material and method: a total of consecutive outbem newborns admitted to nlod from , . to ., . were enrolled to the study. babies who died or were discharged from the unit within hours of treatment were excluded from the study, mean birth weight was g (+/- r), mean gestatational age was weeks (+/- . wks), mean age at the admission was h (+/- hi. multiple (~_ j organ system failure occurred jn . % of babies at the admission./~tertal lactates were measure/at the admission, among - hour and - hour of n[c'lj therapy. outcome was defined as a mortality and length of nicu stay. results" survival rate was . %, mean length of nicu stay for survivors was . days (+/- . day). we found high lactate levels at the admission in . % babies (~ . % with levels above . retool/i). the mean arterial lactate concentrations for nonsurvivors were signiftcahtly higher than for survivors durin~ consecutive da~ as follows: objectives: the purpose of our research was to analyze the frequency of bronchial asthma (b.a.) exacerbations in pregnant women and health status of infants. methods: the research was based on the epidemiological investigation and prolonged observation of pregnant women with b.a. during the gestation period. remission of b.a. before the pregnancy in excess of years was recorded in patients ( . %), patients ( . %) reported a - year remission and patients ( . %) had a remission lasting less than months before they became pregnant. results: seven patients ( . %) developed medium attacks in the second half of pregnancy, four patients ( . %) experienced light attacks of b.a. asthma attacks were most frequently caused by acute respiratory diseases and stress factors. in two cases with grave manifestation of b.a., the pregnancy ended in abortion within the first - weeks due to the frequent and heavy choking attacks. to fight b.a. attacks, five patients used adrenomimetics (salbutamol, becotid) in sprays, six women were administered theophyllinum and salbutamol in the form of tablets during - weeks. a significant portion of pregnant women with b.a. ( %) exhibited frequent complications during pregnancy (toxemia, late gestosis, threat of miscarriage). our findings prove that babies born from women with b.a. of domestic and pollen origin had a low body weight ( - gr), functional immaturity and chronic antenatal and intranatal hypoxia twice as often as the infants born from healthy women without allergic background. conclusions: preventive treatment of women with b.a. prior to pregnancy is required to maintain a stable remission of the disease, which is a key to having healthy children delivered by mothers suffering from b.a. introduction. intracerebral hemorrhage (ich) is a common event in human prematudty, affecting about % of newborns weighing below g who are born before weeks of gestation, however, little is known about the pathogenesis of ich with exception of the prematurity of the brain itself, (birth) trauma, and asphyxia. the postischemic production of oxygen free radicals (ofr) dudng reoxygenation as a cause of brain damage has been demonstrated in animal research. since almost all preventive antioxidant activity of plasma is associated with ceruloplasmin and transferdn we investigated the association of such iron-oxidizing resp. iron-binding proteins and ich. we could demonstrate significantly reduced levels of both, iron-oxidizing and iron-binding proteins, in premature asphyxiated newboms pdor to development of ich. an increase of suparoxide after hypoxia in the presence of iron ions facilitates the formation ofthe highly reactive hydroxyl radicals. our data support the theory that ich may be caused by ofr, which can damage any sensitive tissue including growing endothelial cells. the estimation of transferrin-saturation and measurement of ceruleplesmin levels might help to identify an infant at dsk before the onset of ich. with the new medos | hia-vad | cardiac assist system the missing tool in the armamentarium of cardiac surgeons is available in two pediatric sizes: i -ml and -ml pump volume. the right sided pumps are % smaller for biventricular use. between february and may we implanted this assist system in children. the indications and demographics are indicated in the following table (left ventricular assist device-lvad, right vad-rvad univentricular vad-uvad, post cardiotomy cardiac failure-pcf, dilated cardiomyopathy-cmr bland white garland syndrome-bwg, tetralogy of fallot-tof, hypoplastic left heart syndrome-hlhs). objectives: evaluate tile effeci'of inhaled nitric oxide (no) as puhnona] t vasodilating agent ill tile posloperalivc period after correclion of congenital heart defects in infant. patient n.l: kg, lnonlhs, down syndrome undenvcnl rep~fir of atrioventricular septal defect (avsd). after surgery the puhnonary arlcry pressure (pap) slowly rose to tile syslemic dcspilc tnaximal eonvcnlional fllerapy (fentanyl mcg/kg/h, hypocapnia of mmhg and metabolic alcalinization). no was delivered into tile inspiratory branch of!be breathing circuit at ppm, and the gas aoalyser for no and no (polylron dmger) were situated at the espiratory branch, a rapid dccrcasc of pap io i/ of systemic was obtained with a dramalic improvement. no was continued at ppm for six days and the baby was exlnbated if! days after surgery and discharged from the icu days after. patient n. : . kg, monlhs, onderwen! repair of avsd. the day after surgery the systemic oxygen salnralion was % wilh a pap at % of systemic. two hours of c wenlional therapy failed o improve ihc patient and no administration was slarled at ppm. so dramatically incrcased to %, but the pap dropped only to % of syslemic. nevertheless ihe clinical conditions improved and the no administration could be reduced at ppm in the following days. she was extubaled days after surgery and discharged from the icu days after. patient n. : kg, 'ears. underwen| hearl tral~splantalion for congenital heart disease with moderate hypoplasia of pulmonary arlcrics. at the end of cardiopulmonary bypass the transpnlnlonary al~erio-venoas gradient yeas higher than mnfflg and we speculaled !hat w'ls due to a degree of puhnonary vasocostrictiont. the nsnal dose of no was otilised, however no significant modilicalion of pulmonary pressure or systemic oxygen saluralion was noled, and after h no was discontinned. tile palienl was carried io the icu with maximal inotropic support, extubated after d;b's and disclmrged from the icu after days. in all patient no major adverse effect relaled to no admilfistration ",','as holed. conclusion: in our experience no ms a pulmonary vasodilaling agent is effective and easily adjustable to tile palienls requiemenls, however its use remains limited ill those palienl ill whoin tile alnonll! of fixed inlllllojliify vascular resistance is predominanl. we report the use of ecmo support in two unusual cases of severe tracheal disruption in which it had become impossible to achieve adequate ventilation. case : severe tracheal laceration due to aspiration of a share forelan bodv: a previously healthy month old toddler was referred for ecmo following aspiration of a porcelain foreign body (with razor sharp edges) which had become embedded in the right mainstem bronchus with massive extrusion of air. this was removed on veno-arteda[ ecmo support, as the patient was unventilatable prior to bronchoscopy due to ongoing airieak. ecmg was continued after bronchoscopy to permit airway healing without the presence of an endotracheal tube. unfortunately, an extensive pulmonary haemorrhage on day of ecmo necessited re-exploration of the airway. this revealed a posterior tracheal tear from the cricoid to the middle of the right lower lobe. following repair the patient was left on ecmo support together with high frequency oscillation ventilation (hfov), the latter being used to minimise potential aideak and maximise alveoli recruitment. ecmo was weaned after days ( hours) -the patient was extubated weeks later. case : tracheal wound dehiscence due to seosls -tracheal transelant on ecmo: a month old infant with a c[inically significant congenital long segment tracheal stenosis and left pulmonary artery sling underwent resection of the stenosis, followed by primary reanastomosis. this was complicated, days later, by severe mediastinitis and complete dehiscence of the anastomosis. an autologous pericardial patch was used to repair this, however, the tracheal wound again dehisced days later making mechanical ventilation impossible. in view of ongoing sepsis and a severely disrupted trachea ecmo was the only possible form of support. following resolution of the local sepsis ( days) a definitive procedure in the form of a tracheal homograft (transplant) was undertaken on ecmo. the patient was managed on ecmo and hfov for a further days, the hfov being used to optimize rapid lung inflation. unfortunately this patient died months after weaning from ecmo due to complete disintegration of the homograft, which was not deemed reparable. conclusions: ) ecmo can be used in the acute management of oxygenation when there is major airway disruption making mechanical ventilation impossible. ) hfov was a useful adjunct in aiding recruitment of lung volume on ecmo in these two patients. backoreund: persistent pulmonary hypertension of the newborn (pphn) consists of a heterogenous group of diseases ranging from transient reversibte pulmonary hypertension to fixed primary malformations of the lung (primary pulmonary dyspfasia-ppd). inhaled nitric oxide (ino), a selective pulmonary vasodilator, has been proposed as a treatment for severe pphn. obiective and methods: ino was administered to near term neonates with severe persistent pphn, oxygenation index > and echocardiogrephic evidence of pulmonary hypertension, in order to further determine the clinical role of ino in the treatment of pphn. the response to ino was also analysed retrospectively to examine whether this could be of diagnostic value in differentiating at an early stage patients with reversible from fixed causes of pphn results: twenty one of the patients studied responded to the initial trial of no ( ppm x minutes), as defined by a greater than percent improvement in pad as well as a fall in the el to < . these patients were continued on ino therapy, with patterns of response emerging: pattern babies (n= ) continued to show a sustained response to ino and were successfully weaned from it within days -all survived. pattern babies (n= ) failed to sustain their response to ino over hours, as definded by a rise in the el > . six survived, five with ecmo. pattern babies (n= ) had a sustained dependence on ino for - weeks. all three died and lung histology revealed severe primary pulmonary dysplasia (ppd). patients with ppd (pattern ) not only required ino for longer periods of time than did the sustained responders (pattern ), but also required significantly higher doses of ino we report on the air transport of paediatric intensive care patients. these transports fall into three categories: ) retrieval of critically ill neonates and paediatdc patients referred for either ecmo or inhaled nitric oxide (ino) (n = ). one patient was transferred on ind. mean transfer time . hours (se + . hrs). ) long distance international transport using chartered aircraft (n = ). the indications for these transfers included both urgent retrievals for cardiac surgery and semi-elective transfer of stable patients back to their referring unit following treatment in tertiary centres. mean transfer time . hours (se + . hrs) ) long distance international transport using commercial aircraft (n = ). indications for transfer were either semi-elective retrieval for tertiary treatment or the return of stable chronically ventilated patients to their referring hospitals. mean transfer time hours (se _+ .fhrs, longest hrs). the transport team consisted of a paediatric intensive care doctor of at least registrar grade and a registered sick chidrens nurse with intensive care experience. the administrative components of the transfer (ambulances, airlines, customs) were managed in collaboration with companies specializing in air ambulance transfers. outcome: all the patients were safely transported to their destination without mortality or morbidity. complications durino transfer ir~lv~; ) patient complications -semielective endotracheal tube change and central access needed in the only patient brought to the commercial aircraft by the referring hospital (all others retrieved directly from referral hospital), seizure in patient with known encephalopathy, severe cyanotic spells in patient with fallots tetralogy who was retrieved for urgent surgery for this indication ) mechanical compfications -ventilator failure, incubator battery failure, oxygen regulator failure -all occurred with equipment sent from referral hospital, this was unfamiliar and unchecked by our transport team -it was not the decision of the transfer team to use this equipment on this single occassion. ) administrative complications -confiscation of incubator battery by airport security police, excessive delay by custom officials ( hours) in the airport. the incidence of such problems were felt to be low and unpredictable. in conclusion: mechanically ventilated paediatric patients can be safely transported on both chartered and commercial airlines. these transports are best accomplished by trained intensive care medical and nursing staff with the backing of an air ambulance organization competent in arranging the necessary administrative details. it is essential to use your own equipment and to retrieve the patient _directly from the referrin(] hospital to minimise ootential complications. our experience with anaesthesia for paediatric electromyography _w_._pla_ti_k_a_n_o_v, r.eousseff, k.pavlova, d.marinova dpts. of anaesthesiology and int. care and clinika] neurophysiology, med. university, pleven, bulgaria ~)_b_j#~ti_v~. to t~st a " heavv sedation " regimen of anaest-es~a for the purpose of paediatric electromyography d#s~gil~ non-randomized,non-blinded human trial in the seting of an uriiversity hospetal. _m_a_t_eri_a_is_a_nd_ m_e_th_od_s_. children,asa i-if,median age years,range - who undervent eleetrcmyography required anaesthesia. they recieved low-dose ketamine + i~iazepam or midazolam via musculary route( children,age - yrs,ketamine , mg/kg, diazepam - mg total dose ) or per os ( children,ketamine - mg/kg,diazepam , mg/kg or midazclam , - , mg/kg ) _resu_l_t_s. - minutes after medication a state of heavy sedation with weak spontaneos and stimuli-provoked movements was achieved in all children, that lasted - minutes and allowed adequate needle emg and nerve conduction investigation. children recieved additional , - , vol.% halothane during the placement of the needle. non -invasive blood pressure , breath and heart sounds and hb sad by pulse oxymetry were monitored.none of the older children disclosed memories of pain when asked after they regained adequate verbal contact.no complicationes were observed. antenatal maternal steroids reduce the risk of periventricular-intraventricular hemorrhage in very premature neonates treated with natural surfactants. i.apostolidou, c.papagaroufalis, g.touloumi, m.xanthou, n.kalpoyannis a' and b" neonatal icu "ag. sophia" children" s hosp. athens, greece. dept of hygiene and epidemiology, athens university, greece. obiectives: the aim of the study was to evaluate the association of periventricular-intraventricular hemorrhage (p-ivh) in surfactanl treated premature neonates with pre-and postnatal variables. methods: the population of the study was neonates admitted during the years to , with gestational age _< weeks and severe respiratory distress syndrome (rds) (mechanical ventilation and arterialalveolar oxygen tension ratio (ajapo ) < . ), who received rescue therapy of at least two doses of natural surfactants (alveofact or curosurf) and examined with ultrasound and/or autopsy for the presence of p-ivh (papile's classification). the examined factors in each neonate were the following: gestational age, birth weight, sex, multiple pregnancy, antenatal maternal steroids (complete and incomplete course of betamethasone), a/apo before the administration of the st dose of surfeclant, delivery, apgar score at min, type of surfactant, pneumothorax and patent ductus arteriosus. the statistical methods used were x and one-way analyses of variance followed by logistic regression medels, results: the incidence ot p-ivh was . %. three factors were found to have an independent relation to p-ivh (final logistic regression model): gestalional age, a/apo before surfactant administration, and antenatal administration of maternal steroids (complete and incomplete courses). for every weeks of lower gestational age the neonates had an almost doubled associated risk of p-ivh (or: . , % c : . , . ). for every . on average decrease of a/apo before surfactant administration the risk of p-ivh in the neonates was . times higher ( % ci: . , . ). the neonates whose mothers received antenatally steroids had only one tenth of the risk of p-ivh of the neonates whose mothers had not (or: . , % ci: . , . ). conclusions: our results suggest that the antenatal administration of maternal steroids, even less than hours before delivery, reduce the risk of pqvh in very premature neonates treated with natural surfactants, whereas the small gestational age and the lung immaturity still remain the main risk factors tor the development of p-ivh. we analysed retrospectively the management of ( boys, girls) accidental ingestions of foreign bodies in children (mean age : . years, range : months- years). no child had ingested more than foreign object. the majority of the ingested foreign bodies were : coins (n : ), toy parts (n : ), jewellery (n : ), batteries (n : ), "sharp" materials such as needles and pins (n : ), "large" amounts of food (n : ). impaction of food occurs more frequently in children after oesophageal reconstruction in cases of oesophageal atresia. although according to literature "coca-cola" is reported to be effective, this was not seen in our experience. / patients had minor transient symptoms at the moment of ingestion, such as retrosternal pain. only children experienced severe manifestations (cyanosis, dysphagia). in these children, endoscopy revealed oesophageal and gastric erosions. children were seen at the emergency ward within a few hours after the accident ( mean : hours, range min. - hours). chest and/or abdominal x-ray was performed as first-line investigation ( / objects were radio-opaque), and revealed an (unexpected) oeeophageal impaction in children. in / the foreign body was in the stomach. batteries, sharp objects and objects trapped in the oesophagus were removed, either by endoscopy or by magnet-extraction whenever possible. the outcome of the patients was excellent. no complications were observed. extraction is recommended in symptomatic patients, and whenever the foreign body is trapped in the oesophagus, or if the foreign object is "sharp" or a battery. objectives: two strategies were used for management of malignant diphtheria in children aged from . to years. methods: protocol n consisted of intravenous administration of diphtheria antitoxic serum, prednisolone ( mg/kg bw/day), plasmapheresis and supportive care. protocol n included the use of antitoxic serum against the background of high-dose dexasone ( - mg/kg bw/day), hemocarioperfusion and a preventive use (before the clinical manifestation of myocardial damage) of inotropic medications, inhibitors of angiotensin-converting enzyme and pentoxyphylline. each of protocols included the monitoring of serum toxin (diphtherin) levels. results: the group of patients treated according to the protocol n consisted of children with malignant diphtheria, of them with severe malignant diphtheria (grade and ). all patients exhibited the circulation of toxin during at least three days after the start of treatment. all patients with severe grade of disease demonstrated heavy cardiovascular disturbances associated with malignant diphtheria. of the children in the group died seven. the children of the second group were treated according to the protocol n . out of total of patients of this group. patients had severe malignant diphtheria. in all children a significant reduction in serum toxin level was revealed after hemocarboperfusion. in all but one case the satisfactory control of cardiovascular function on was achieved. of children admitted to the trial survived, one child with malignant diphtheria of grade and congenital filbroelastosys of the left ventriculum died. the severity of neurological complications was similar in each of groups. conclusions: the use of hemocarboperfusion, high-dose dexasone and early prevention of heart failure as a adjunct to the standart treatment has been shown to be of benefit in the management of malignant diphtheria. t. schaible, i. reiss, j. m er, l. gortner med. university of lqbeck, children's hospital, kahlhorststr. - , l~beck, germany surfactant therapy seems a promising approach for the treatment of the biochemical and biophysical abnormalities of the pulmonary surfactant system in severe ards. patients and methods: over a months period non-neonatal pediatric ards patients (age - months) in a "pre-ecmo"-situation (oi over h) were treated with bovine surfactant (alveofact| the underlying conditions-of ards were pneumonia ( ), sepsis ( ), immunosuppression ( ), near drowning ( ), neurogenous ards ( ). a total of - mg/kg b.w. was applied in several fractions. before surfactant therapy, we first tried different ventilation (best peep-finding, inversed i/e-ratio, hfo-ventilation) while monitoring the pulmonary mechanics. for hemodynamic stabilisation both norepinephrine and epoprostenol were used to optimize pulmonary perfusion for max. hrs. if there was no improvement of the oi by at least , further treatment with surfactant was initiated. in addition to surfactant all patients received a treatment with dexamethasone of mg/kg in doses. patients with no benefit (oi remained unchanged or increased within the max. - hrs) were taken on ecmo. results: nine patients improved within hours after surfactant therapy: the oi decreased from a level of (mean, range - ) before our treatment to a level of (mean, range - ) thereafter. in patients we were able to continue the positive effects of our treatment and they could be weaned of the respirator within - days. the other patients got worse despite respiratory improvement, they suffered of multiorgan failure of more than organ systems. the last patient did not benefit from surfactant, he had to be put on ecmo, but died because of a complication (hemopericard)after days. the autopsy of the ecmo-patient showed a pulmonary fibrosis, but the other death were not due to pulmonary failure. conclusion: a different sequential ards treatment integrating surfactant therapy can reduce the number of patients requiring ecmo. but ecmo as a therapeutic tool should be available in centers involved in ards treatment. l.blindl, t.p.le, h.weinzheimer, centre for paediatrics, university of bonn, germany selective reduction of elevated pulmonary vascular resistance by inhaled prostacycliu (pgi) has been reported in adults with acute lung injury, neonates with persistent pulmonary hypertension and in one infant with idiopathic pulmonary hypertension. we report on the effect of aerosolized prostacyclin in two children with secondary pulmonary hypertension. patient : in a boy with down's syndrome an avsd had been surgically corrected at month of age. at , yr of age a catheter examination revealed a pulmonary vascular resistance of % of systemic vascular resistance in room air and at an fin of . . prostacyclin ( . mcg/ml) was administered with a jet nebulizer at an fin of . . pvr declined to . systemic vascular resistance and returned to baseline after stopping pgi-inhalation. subsequent intravenous infusion ( ng/kg rain) had to be stopped after minutes because of systemic arterial hypotension. patient : a month old male infant with bronchopulmonary dysplasia developed suprasystemic right ventricular pressure inspire of therapy with oxygen and nifedipin. while he was spontaneously breathing % oxygen via face mask pao was mmhg, arterial ph was . . systolic arterial pressure was mmhg, a rv-ra gradient of mmhg was measured by cw-doppler. while fio was maintained aerosolized prostacyclin was administered over minutes. rv-ra gradient was mmhg, systemic blood pressure mmhg, pao mmhg. two hours later nitric oxide ( ppm) was inhaled at an fio of ( , . rv-ra gradient declined from to mmhg, systemic systolic blood pressure remained stable at mlnhg. discussion: sporadic experience shows that aerosolized prostacyclin selectively reduces elevated pulmonary vascular resistance in some patients. in patient the poor response to inhaled pgi compared to inhaled nitric oxide may be explained by the fact that the action of pgi is not independent from endothelial function, limiting it's effect in severe vascular disease. during the last two years ( - ), infants weighing less than gr. admitted to our referral unit. thirty four of them ( %) survived, ( % of infants weighing - g and % of infants weighing - gr survived) for the years - - the survival of these infants was % and for the years - - , % (p< . ). we analyzed the perinatal and neonatal factors influencing the outcome of these infants. the comparison among neonatal survivors ( ) to neonatal deaths ( ) shows: gestational age: . w ( ) to . w ( ) (s). birth weight: . g ( ) to . ( ) (s). apgar score: , ( ) to . ( ) (ns). presentation and mode of delivery: breech presentation is associated with higher incidence of neonatal deaths. i.v.h. (at the age of weeks): no one of the survival infants had evidence of i.v.h. respiratory problems: intubation, at the admittance of the infants . ",,( ) to % ( ) (s) use of surfactant: % ( ) to % ( ). bpd observed in % of the babies and only one was dependent on oxygen at home. antenatal betamethasone was given in % of the mothers. in conclusion: ) a great improvement in the survival rate observed in these infants the last years in our unit. ) factors with positive effect are increasing gestational age and birth weight, the absence of i.v.h. and the use of surfactant. the breech presentation and the severe respiratory problems increase the incidence of death. animal experiments demonstrated, that brain temperature determines the amount of neuronal damage caused by hypoxia and that mild hypothermia may have a protective effect. until now there is no method described and evaluated to measure brain temperature in neonatal intensive care units. we non-invasively measured brain temperature analogues, nasopharyngeal (tnasoph) and zero-heat-flux temperature (zht) at the temple whereby under zero heat flux surface temperature represents deep head and thus brain temperature. the aim of our study was to investigate the practicability of the method, the relationship of the two brain temperature analogues to rectal temperature (trect) and their dependence on insulation, thermal environment, body activity and time course. we investigated healthy preterms less then weeks postnatal age (gestational age +_ . wks; x + sd, weight +_ g) in an incubator. tnasoph was measured by a thermistor within a feeding tube, advanced to the nasopharynx, zht temple by a thermistor and a heat flux transducers both covered by an insulating pad, and trect thermal environment was characterised by operant temperature (tair . . + twall . ). body activity was video taped. measurements were performed during the following interventions: i/ insulation increased by turning the temple with sensors onto the mattress ( rain). ii) insulation increased by a cap ( min), iii) min after its removal, iiii) increased operant temperature by . + . ~ ( min). results: seven children with ea had a gasless abdomen, the endoscopic procedure excluded ( ) or diagnosticated an upper pouch fistula ( ). in patients who suspected "h" fistula ( ) broncoscopy has strong advocated method to make diagnosis and established cervical approach. from july newborns with ea and lower pouch tef received a selective transtracheal incannulation. we were not able to proceed just in case with congenital subglottie stenosis. in these patients we provided gastric drainage by radiopaque and flexible - french catheter. the knowledge of the precise anatomic position of tef consent to adjust the tip of the endotracheal tube in order to achieve best ventilation. the presence of the catheter through the fistula helps the surgeon to identify, it quickly. no complications were correlated to the procedure and no babies had early pneumonia. alimentary continuity was achieved in all patients ( primary anastomosis, resections of tef, oesophagocoloplasty and died with gastrooesofagostomy). the late mortality . % ( ) was only directly related to the severity of associated malformations. conclusion: the advantages of this technical approach are unquestionable for the anaesthesiologist and the surgeon. in our experienc e the procedure improves perioperative management of babies and appears to be safe. relation between cytokines, prethrombotic markers and endotelial injury markers in children with septic shock objectives: to establish the relationship between cytokines (tnf, il- , il- ) prethrombotic markers (d.d., pcam) and endothelial injury markers (tm, uwf) in pediatric patients with sepsis and bacteriemia without shock, and patients with septic shock. design and methods: prospective study, children ( months- years) were admitted in our picu in with the following diagnosis: bacteriemia ( ) sepsis ( ) and septic shock ( ) according to jacob's r f criteria. measurements: il- , il- , tnf, tm, vnf, d.d. pcam and routine laboratory data on admision, , , hours and on discharge. the prism (pediatric risk of mortality score) was also recorded. results and conclusions: two patients in the septic shock group died. significant differences were found between non-shock and septic shock patients in relation to tm, dd, pcam, il- , il- and tne high levels of tnf and il- are closely associated with the severity of septic shock with purpura in children. low levels of pcam on admission were associated with severe shock. who underwent open hea~nt surgery, hypervotaemia with or without oliguria was the most frequent reason to start pd ( %). in patients pd lasted less then one week and there were no complications; in patients it lasted - days (one child had a peritonitis). instillation of dialysis fluid into the peritoneal cavity was associated with a significant increase in central venous pressure. there were no significant changes in cardiac output or arterial oxygeu saturation. in all patients pd dhnjnished fluid overload or improved the metabolic status. patients ( %) survived the postoperative course and all had complete reintegration of renal function. conclusion: pd is a useful method to treat the fluid overload and acute renal failure in paediatric patients following open heart surgery with file effects of little importance on the cardiovascular fimction. obieetives: with the marketing of computerised systems for lung function testing in newborns, there has been an increasing interest in clinical approaches. percentile curves of pulmonary parameters permit an appropriate and clinically useful interpretation. however, the manual evaluation of the results using different curves is an impractical technique. therefoi'e a computer programme was developed. methods: the percentiles ( %, %, ~ %, %) of the most important pulmonary parameters were determined non-parametrically in weight-classes. for the calculation we have taken results of our own as well as other laboratories using a meta-analysis of reference studies. in all, individual data of - healthy newborns ageing between - days were collated. using these percentiles, for every parameter in relation to the body-weight the cumulative distribution was calculated approximately using piecewise linear and exponential functions. as shown in the figure the results of computing are represented numerically as well as graphically and can be included in the patient report. conelusions: clinic~d experiences with the programme have shown that representation of all measured parameters on standardised % scales allows an easy interpretation at first sight and improves the detection of pathologic patterns in the parameters. ")supported by bmft, fp "risikoneugeborene" prism (pediatric risk of mortality) score is a well known, already validated scoring system that quantifies severity of illness based on routinely clinical and laboratory variables measuring physiological instability. once computed the score by summing up the weights corresponding to the most abnormal value recorded during the first hours, the overall risk of mortality can be predicted by using the coefficients estimated by a logistic regression where prism score is the main independent variable. (pollack mm et al, -pediatric risk of mortality (prism) score. crit. care med. ; : - . to assess the applicability and validity of prism in the italian setting we launched out a prospective data collection in a sample of pediatric icus. measures of calibration (goodness of fit statistics) and discrimination (receiver operating characteristics and area under the roc curve) are planned to be adopted in the cohort of patients recruited during year period. as the validation study started on july , data collection is still on going and validation analyses will be carried out on july . up to now centers recruited cases. at present, characteristics of the sample recruited are the following: most of the patients were male ( %); the mean age is years with % of patiens having less than days; more than half were medical cases ( %) admitted from emergency room or from hospital floor ( %); % cases were admitted with an organ failure while % to be intensively monitored. icu-mortality was l %. the paper will present final results of calibration and discrimination analyses that will be carried out in the whole sample and across subgroups known to differ in terms of clinical relevance and prognosis. if calibration and discrimination assessment will produce not satisfactoty findings, a customization of the current coefficients will be made allowing a formal comparision of previous and new parameters. jf riera-faneao, m wells, j lipman. baragwanath intensive care unit, university of the witwatarsrand, south africa. [background the prism score is designed to assess the likelihood of death in ipaediatdc icu patients, using only acute physiological disturbances, age and [operative status to predict mortality. there is no evaluation of chronic health status, [including malnutrition. this may significantly affect its ability to accurately predict outcome in a population where malnutdtion is common. aim to determine the influence of nutritional insufficiency, as indicated by a low weight-for-age on outcome prediction by prism. patients & methods we analysed prism, weight and demographic data co ected prospectively from consecutive paediatdc icu admissions over a year pedod. a proportional weight (pwt) was calculated as a percentage from the th centile of the who weight-for-age growth charts. the pwt was compared for survivors and nonsurvivors, and mortality compared for pwt categodes nho wellcome classification). multivariate statistical techniques were used to identity associations with non-survival and to develop a modified logistic regression equation including a measure of i nutdtional status. receiver operating characteristic (roc) analysis was performed including and excluding patients with low pwt for the odginal and modified equations. results non-survivors had a lower weight than survivors ( . kg and . kg medians p = ) a lower pwt ( % and % medians p = . " . the incidence of malnutdtion , in our icu population was %. the mortality of manoudshed patients was' significantly increased (p = . ), with a good correlation with the degree of malnutrition. the accuracy of prism was significantly improved when malnourished patients were excluded from the analysis (roc value increased from . to . ). ! logistic regression and discriminant analysis identified a significant association between prism, pwt and outcome; age and operative status were not significantly related to mortality. the use of a modified equation including the raw prism score, pwt category and age can significantly improve the discriminatory power (az dm/elopmental sample . , az validation sample . ). the modified formula is: legit = - . + . *prism score - . *age + . *weight category, where the probability of mortality is exp(iog/t)/ + exp(iogio. discussion although we can improve the prediction of mortality by a modified or recelibrated formula, this still does not compare with the reference prism population. the need for validation of the score itself, in the association with outcome of the acute physiological variables themselves, is thus apparent. we conclude that while the odginal prism formula can be improved significantly, a modification of the basic variables in this and other third wodd populations may be essential. a high incidence of malnutrition is an independent risk factor of mortality, and an important cause of the poor discriminatory performance of prism. in order to improve the accuracy of prism, nutritional status should be taken into account. objectives: to assess the value of inhaled no to differentiate between pulmonary vascular constriction or fixed anatomical obstruction. methods: we assessed the response to ppm inhaled no in patients( m, f, median age . months, range day to years) with signs of increased pulmonary vascular resistance, there were pre and postoperative patients. patients were divided into responders(+) or non-responders(-). a positive response was defined as a % reduction in pulmonary arterial pressure and pulmonary vascular resistance(pvr) or in the presence of a left to right shunt, a fall in pvr accompanied by increasing pulmonary blood flow. left atrioventricular valve atresia + mustard pat: pulmonary atresia vsd: ventricular septal defect asd: atrial septal defect pda: patent ductus arteriosus tapvc: total anomalous pulmonary venous connection the responders( / ) were characterised by left to right shunts or pulmonary venous hypertension( / ). patient# was weaned from ecmo with inhaled no. patient# , without congenital heart disease, underwent a lung biopsy which confirmed reversible pulmonary vascular changes. patient# had a pulmonary hypertensive crisis which responded to no. all non-responders( / ) had evidence of anatomic obstruction to pulmonary blood flow (# , , )or a low pvr(# ) on subsequent cardiac catheterisation. in patient # , lung biopsy confirmed severe obliterative vascular disease. conclusions: inhaled no appears to be an effective pulmonary vasodilator. a failed response may be evidence of either irreversible pulmonary vascular disease or a residual anatomical obstruction which may be surgically remediable in the postoperative cardiac patient. therefore, inhalation of no may be a useful diagnostic test to differentiate between fixed anatomical obstruction and reversible vasoconstriction. results: during these years, the incidence of sdra was . % of the total of admissions. the most common etiology was meningococcic septic shock. since , there is a decrease of its incidence. (from % to %) and an increase of pneumonia and immtmodeficiencies. mean age of our patients was , years ( % males, % females), total mortality by sdra was % and there is an increase up to % since mean time of stay of the dead was , days and , days those who survived. although during the late years we offer in the picu a better attendance quality to the patients with sdra and the mean stay is longer, both for those who die and for those who survive, mortality of patients with sdra have increased. the incidence of sdra secondary to the septic shock of a meningococcic etiology have decreased. on the contrary, the sdra secondary to infections by opportunistic germs in patients with congenital inmmunodeficiencies or acquired immuodeficiencies have a tendency to increase. in our series, this change of aetiology is the responsible for the increase in mortality. hospital infantil unlversitario "virgen de roclo". sevilla. espalqa aims:to assess the incidence, etiology, clinical course, sequelae and mortality of the patients admitted to a paedfiatic intensive care unit with the diagnosis of severe traumatism. material and method: cases of severe traumatism in children admitted to our icu in the period from january to june were reviewed. age of patient ranged from months to years, % were males. in our series, % of cases suffered traumatism due to a traffic collision and % had a fall from a considerable height. only in one case was traumatism due to violence to the child. we assessed the first assistance received in % of cases: where was it performed, interval of time since the accident, and steps taken. these data were also studied in relation to the latter evolution. results: % of our patients suffered cranioencephalic traumadsm (ct); in % it was an isolated picture and in % of cases was associated to other lesions. there was participation of thoracic and/or abdominal organs in % of cases. % of cases presented important maxillofacial involvement. only one case presented serious cervical medullar lesion. mortality in our series was . %. in . % important sequelae remained. all of these patients presented tepas on admission equal or lower than . % of those with traumatises had slight sequelae. . % of the total evolve towards healing. a polytraumatized child is a patient that benefits considerably of it admission in a paedriatic !cu. the rapidity in receiving first aid and its quality are essential to avoid sequelae and to make mortality decrease. after unilateral lungtransplantation % of the patients develop a lung failure with decrease of perfusion and increase of pulmonary blood pressure in the transplantated lung. the improvement of perfusion is an importent task in the postoperative period. case report: a year old girl with idiopathic pulmonary fibrosis received a left sided single lung transplantation. during the early postoperative period occured a higtter demand of oxygen and an increasment of the pulmonary vascular resistence in the left lung. the pulmonary ventilation and perfusion scintigraphy indicated in comparison with the right lung a reduced perfusion of only % in spite of a ventilation of % of the transplanted lung. to improve the perfusion of the transplant we administrated per inhalation prostacyclin in a maximal dose of ng/kg/min. the arterial blood pressure decreased but the perfusion continued nearly at the same level. during the following administration of ppm no in the respiratory air we achieved a significant reduction of the respiration pressure f~m to nun h and of the pulmonary arterial pressure. the perfusion in the transplanted lung increased to ca/of the total pulmonary perfusion. after days of administration with no we were able to withdraw the axtifical respiration without any following complications. conclusions: the perfusion of transplanted lungs is a major proble_r~ in the postoperative period. this case demonstrated the advantage of no towards the inhalativ application of prostacyclin. no showed a significant improvement of perfusion in the transplanted lung of a year old girl. results: a total of children with ards were treated with bovine surfactant (alveofact| cases were evalable. the median age was . years (range weeks to , years). in six cases ards was associated with pneumonia, in two cases with lung hemorrhage; in one case isolated ards followed hemihepatectomy. the first surfactant application was performed with a median latency of clays (range - days) after first symptoms of ards witha median doseof mg/ kg (range - mg/kg). in patients doses of surfactant were applied. during the hour before therapy, the median pao / fio -ratio was - . within min. after application of exogenous surfactant the pao / fio -ratio increased to with successive decrease over a period of hours to . accordingly, an increase in pao and oxygen saturation and (less significant) a decrease in ventilation parameters could be observed. analysis of broncho-alveolar lavage before surfactant application in children receiving repeated doses revealed in most examined cases either clear surfactant deficiency or pathological function. of treated patients survived ( of the , respectively). of the surfactant doses were applied in the surviving patients.conclusions: the application of exogenous surfactant in children with ards caused a significant increase in oxygenation, which declined over a period of - hours. the effect often could repeatedly reproduced, in one case after applications. the increase in oxygenation often allowed the reduction of fio and/or the inspiratory pressure. no side effects were observed after exogenous surfactant application.in many cases the application of surfactant wag too late after first symptoms of disease (median latency days). ards mostly due to pneumonia seemed to respond to surfactant therapy less well or not at all. permanent junctional reciprocating tachycardia (pjrt) is the most common incesant supraventricular tachycardia (svt) in children. it is usually drug resistant and its onset in early life has been associated with dilated eardiomyopathy. we report our clinical experience with patients detected antenatally and another diagnosed at months of age. method.diagnosis: negative p waves were detected in leads ii,iii and f, p'r > rp" and there was not warm-up at tachycardia onset.clinical records, ekg,x-rays, echo and holter were reviewed. ep studies were undertaken only with therapeutic purposes. results. in a year period patients under y of age fullfilled diagnostic criteria; were detected prenatally ( - weeks) and one was diagnosed at age mo. the fetuses had intermitent svt during gestation. all of them had pjrt in the first month of life at rates between and bpm. they were admitted to the icu but did not develop signs of heart failure. they were controlled with digoxine (d); d and quinidine; d and propafenone in to days. one was in sinus rhytm until age y; he then showed persistent pjrt over % of the day on repeated holters and underwent successful radiofrecuency catheter ablation (rfca).the other two patients showed initially a lowering of tachycardia rate followed by sinus rhytm for over % of the day (follow-up ran and y). the mo. old infant was admitted to the icu in severe cardiac failure. echocardiogram showed marked systolic dysfunction (shortening fraction %) treatment with digoxine, amiodarone and propafenone were unsuccessful despite lowering heart rate to ; rfca was performed at m. of age with restoration of sinus rhytm and rapid recovery of contractility. all patients were given atp at admission with transient ( to see) recovery of sinus rhytm. ff,s clinical course of pjrt is variable. atp is useful only as a diagnostic tool. initial treatment with digoxine + amiodarone or propafenone is adviced. rfca is a very useful therapeutic modality and can also be performed in young infants twelve patients ( %) died. these were meningitis, head injury, sub-arachnoid bleeds, status epileptieus, leukaemie, drowning, and multiple trauma. calculated from the a admission day p edialric risk of mortality score (prism), the probability of death (p) ranged from - %. of the deaths, i were predicted by prism analysis except for the leukaemie patient (p i%) who died from haematological complications following chemotherapy. two children predicted to die (p % & %) survived. the median length of stay was days (range - days). patlents( %) received ventilatn~ support and patienta( %) were transferred to specialist units ( neurosciences, liver, cardiac, bums). this data supports the view that many paediatric patients are being adequately treated in a dgh icu. meningitis and other neurological illness caused the majority of deaths and respiratory problems caused most admissions. most deaths ( of ) occurred within a few hours of admission. ectopic junctional tachycardia (ejt) is one of the most dangerous arrhythmias in the postoperative setting of congenital heart defects since it does not respond to antiarrhythmics or defibrilation. the object of this presentation is to report on two patients who presented f_jt in the early postoperative period and developed intense congestive heart failure which could be controlled after treatment with moderate topical hypothermia. two patients, m and y, diagnosed of atdoventficular septal defect and tetralogy of fallot developed intense heart failure in the early postoperative period. taehyeardia rate was and bpm. medical drug therapy included weaning from vasoactive drugs, iv digitalization and iv amiodarone treatment. there was not response. they were both surfaced cooled by placing plastic bags filled with cold water over the patient's chest and abdomen. temperature was monitored to obtain a central temperature of ~ there was a gradual decrease in heart rate in the following hours ( - bpm) paralel to the degree of surface cooling and clinical course estabilized.both recovered normal sinus rhytm in to hours. there were not significant arrhytmias after the procedure and postop, was uneventful. conclusions. moderate hypothermia is a very useful manuever for the treatment of drug resistant ejt. since it lacks side effects of other antiarrthymics we beleave it should be the treatment of choice for the treatment of ejt in the postoperative patient. present understanding of the pathogenesis of sepsis, based on the theory of systemic inflammatory reaction, has risen new interest in the more invasive methods of treatment, like plasmapheresis, leucapheresis and exchange transfusion (et). obiectives: evaluate the effect of et in the treatment of neonatal sepsis. material and methods: from september to december , a prospective study was carried out, where the severest cases of bacteriologically proven neonatal sepsis (n= ) were treated with et. in total newborns were treated for culture positive sepsis in the intensive care unit during this study period. diagnosis of sepsis was based on the clinical criteria of suspected neonatal sepsis, used by mc harris et al., laboratory data and positive blood culture. newborns with severe congenital malformations were excluded. et was carried out with fresh (less than hours old) adsol-conserved erythrocytes, from which buffy coat had been removed, and same donors plasma, using a slow continuous two-site technique. the mean volume of et was . ml/kg. the effect of et was assessed as a change in the score for acute neonatal physiology (snap), general treatment results were compared with a historical control group of newborns, treated for culture-positive sepsis in the same icu during the first eight months in . students ttest and chi-square test were used in statistical analysis of the data. results: with the use of el a significant decrease in mortality was achieved: death of cases during the study period, compared to deaths among the controls (p< . ). no baby, receiving et, died. the incidence of severe complications did not differ in the two groups. the snap-score showed quick improvement by the first post-transfusion day (p<o. ) and the effect persisted during the five following days. conclusions: we conclude, that the use of et in the treatment of critical cases may help to lower the mortality of neonatal sepsis. it provides a quick improvement in the clinical condition of septic neonates. the granulocyte-colony stimulating factor (g-csf) is largely employed in granulocytopenic patients. experimental studies have' demonstrated the effectiveness and safety of the therapeutic use, nevertheless the human employ is reported almost exclusively in neoplastic patients submitted to chemotherapy and in patients with fungal or pseudomona~ spp infections. the authors report the data concerning three non granulocytopenic children: in the first, o girl years old, affected by pseudomomm aerug/n~a pyeionephritis, the antibiotic therapy was not tolerated in consequence of renal and hepatic failure. the second patient, an infant months old, has been treated with salbactam-ampiciilin, ceftriaxone and chioramphenicol because of haemepldlw iafluem~ meningitis; a late neurological aggravation required the antibiotic therapy recommencement the last, a years old insulin dependent diabetic boy, was affected by cared/do spp systemic infection; the antifungnl therapy w~ not practicable in consequence of renal and hepatic involvement in all the g-csf was administred subcutaneously at the'dose of $ u for days. a significant increase of granulocytes was ever noted already after the second administration until hours after the last dose. clinical signs, fever and biochemical values are promptly influenced positively and all patients are restored to health. no side affects were noted. the granulocyte colony stimulating factor, at indicated doses, can prove of great help in critical patients, in who the antibiotic or antifangal therapies can result toxye or cannot be tolerated. the ~reptococcas p~, among the gram pmltlve~ represents the main causative organism of bacterial meningitis in children, with the majority of deaths occurring within hours of admission, the third generation cepohlosporim were indicated as antibiotic of first choice, and some literature reports have demonstrated no significant dlffereuces in dinical course of patients treated with ce~rlaxoae and of those treated with ampieibin and chlornmphenicol. the authors report the ease of on infant, male, months old, submitted to a neurosurgical interventiol after days the infant became febrile and lethargic and a bacterial meningitis by ~trepmcecctz ~ was diagnosed, in spite of he was given the eoftriaxone therapy.. an amelioration was found only when a systemic treatment with vaucomyein was added. after days an intrathecal administration of vancomyein m~day was started: the norbmlization of the spinal fluid profile was uoted two days later and the infant receve~d progressively. the follow-up after eight months doem't evidentiate motosensorini sequelae-the individuation' of ~cscc~ pmmmsm/ae strains heta-loctam antibiotics resistant requires alternative therapeutic regimens: the k~terity quead vitam and quoad valetudinem of these infections justifies an intrathecal therapy, especially failing o prompt answer to the systemic treatment objectives: to evaluate the incidence of the burnout (bo) of the staff in a picu in a university hospital. the bo is a syndrome charactedzed by many factors like emotional stress, lack of personality and reduced work ability. this syndrome represents a kind of abnormal response in the working habitat, above all, where psychological and personal characters are mostly involved. the symptoms of bo are represented by demoralisation, demotivation, incapability, boredom, isolation up to organic disturbances, like migraine, insomnia, dizziness and gastrointestinal disturbances. the major incidence of this syndrome was found in the hospital staff, especially among the nurses, working in an atmospher of high emotional dsk, just like in an intensive care unit. methods: from january ' till april ' , all the staff of the picu of the a. gemelli hospital of rome, underwent a test to evaluate the bo. the test used was taken from the book "bumout: from tedium to personal growth", by pines and aronson. twenty seven people were studied ( females, males)i out of which doctors, residents and nurses. it was considered sign!ficant as mild bo, a score between - and as severe, the score of bo >. . results: subjects ( %) resulted positive for bo, out of which were females ( %) and were males ( %). the subjects with mild bo were / : was a doctor, residents and nurses. the subjects with severe bo were / , out of which resident and nurses. conclusion: the results obtained show that bo is a condition well represented in the staff of our picu. the category most at dsk seem to be the nurses ( subjects), as well as residents ( subjects), as in literature, which shows a major incidence of the syndrome in younger subjects and having a limited partecipation of functional decision. the results obtained obliged us to start a programme of serial controls so that the subjects most exposed can have a necessary psychological support to react adequately to this condition. the term systemic inflammatory response syndrome (sirs) was adopted by the consensus conference to denote a type of systemic response to severe infection or otherinsults in critically ill patients. when sirs occurs from infection it is called sepsis. sepsis occurs more frequently in persons with perexisting illness or severe trauma. there has been tremendous advances in prophylaxis, diagnosis, and treatment of sepsis. a comprehensive model of the disease progression from sirs to mods should be developed giving priority to severity of illness scoring system and other predictive methods. some recommendations for future clinical trials include: trials should not start with humans. before proceeding to human trials, animal studies should indicate an acceptable risk/benefit ratio. appropriate patient populations must be defined and treatment protocols should be standardized. full and rapid reporting of all results should be mandatory and a central repository of published and unpublished study results could be helpful. accrual at each center should be of sufficient size, and should include the number of patients accrued, mortality rates, and patient characteristics. pivotal trial should be preceded by sufficient pilot or phase ii studies. correct drug dosage and usage should be delineated in pilot studies. large, multicenter, trials should be used to enhance the unversality of trial results. analyses should be planned a priori. definitions for the target population should be explicit, reproducible, and include illness severity scores. outcomes should be relevant reproducible and include both measures of benefit and harm. mods and its reversal should be considered as an endpoint. quality of life should also be considered as an endpoint. the estimators of overall treatment effects should be controlled for base-line prognostic factors and subgroup anaiysis should only be used for hypothesis generation and not to modify the conclusoin of the trial. economic analysis should be included as part of clinical design. evaluatin of source control should be a critical component of any study. standardized clinical mediator assays should be pursued. placebo patients in clinical trials should be studied for a better understanding of the pathogenesis and epidemiology of sirs, evidence based medicine should be used to evaluate the validity of clinical. introduction: use of inhaled nitric oxide (no) as a modulator for optimizing ventilation-perfusion or lowering pulmonary artery pressure is becoming increasingly common. no is a free radical but little toxicological research has been published. clearance of nebulized mtc-dtpa is known to be, a sensitive indicator for early function impaimaent of the alveolocapillary barrier. we investigated whether exposure to no increased clearance of ~tc-dtpa from the lung. methods: three groups of white sealand rabbits (bw . kg) were anesthetized, tracheotomized and paralyzed. groups were ventilated for six hours at pressure regulated volume control, set to deliver ml/kg with a frequency of /rain, i/e ratio = : and peep = cm hzo using a modified servo ventilator (siemens, solna, sweden) with computerized no delivery system. gas mixture per group was either / or / [no (ppm) / fioz]. after six hours of ventilation in these groups and immediately after anesthesia in group (control), ~tc-dtpa was nebulized into the inspiratory line of the breathing circuit and administered as a fine aerosol. gamma counting was measured for minutes, monoexponential curves were fitted to the data and the clearance half-time (t was calculated. the t~/ mean • sd of the different groups were: t~a (mean -sd) h"e,i witl~ arf : di.ff:erent kinds, aged .q-ore mon't.hes to [ gears o : (bodi weight .~rom ., to kg), is presen .... "ed ( i,,~u::trl:e i:ibstraclive d:lse~se... ~ .ards'- ; :~,;,,arf o~ ::entral genes:i s .- , ,~ :inc lud ing men ingeenceph it :is- ~ reye ' s ~yrtdro~e-..#~,bri~:ln pes~.re~nimatior~ disease.." ). int:lrl~]. pa-. "iiulle'i,~s ariel regymes o+ l;mv,l;i"t"v were cle'l'.ermllled by ba- 'i~ier was. about . tuber,, dopamin tiara-:. t.io; was ~.".,,'.r:~r~led. cmv,cppv d~.!"~tion raniled -~rom f to dayns.,~ < .-:in , "t -irl lo;and> davs'-in 'l~atierr~{s i'i"ai s:ltiol~ o ; patterers to imv, simv modee was per.r:)rmed, ~herl pif:' decrease.d to - ml~ar, fi ~ecreased to , . lind less with a = /,,. i:lesq.lts:{ in pat:i.ents e{ group :l, who were tre,~d.ed w&th f'f'v, teoph :i. : . l:i.r~ (is- .mg/kg/day), g lucecdr t icostei~oids ( .... :~;mg/kg/day), when r exceeded in , -.];, times normal va i tea the e aqes/,'!:l"oln ~j,, ite :i.~;::.!;, ~ml"lrj), it was possible 't'(' ce 'e~ e aad]t:..~rom ! . '.' i', to !..'; , - , mml-lg in ~}.. :~.[~ houi,!; ~d'l(:i to ru:}l",g'd!~l:i. e i::h,:~e,'~c['el';i.stil obieetives : this chapter will describe what is knovca of the psychlogical responses of infant and children to hospiuiisation and attendant procedures. the factors which may modify these responses will he discussed and important considemtiorts will be outlined for optimal anaesthetic management and postoperative period of infants and children which will minimised the rise of emotional upset. methods : in this paper the autors will discttssed the probl of: . health children (asa i, ii) facing single uncomplicated surgical elective procedures . various abnormal situations including neurotic children, children facing repeted operations, chronically ill, buaaes and tsaumatically impired ones . unfortunate young patient facing and often expoclting fatal outcome from le "ul'ukaemia, tumors, cystic fibroses or otheq" disease. : management of each child must vary greatly, ifi general the phases of emotional conditioning include home and preadmissiun preparation, admitiun preoperated and operative care and postoperative period. the authors would be happy if the child passes all stages without any trauma which could be prolonged in the future life. introduction ino is used to selectively reduce pulmonary vascular resistan(~e. we applied ino in the postoperative intensive care of patients with pulmonary hypertension and the risk of right ventricular failure after surgical correction of a congenital cardiac defect. methods - ppm no were added to the ventilatory gas mixture using a specially designed equipment (messer-griesheim, germany/austria). indications for application included pulmonary artery pressure > % systemic pressure, critically depressed right, ventricular function or an oxygenation index > . assessment of n oefficiacy consisted of on-off-on measurements according to the clinical stability of the patient including hemodynamic parameters, pulmonary gas exchange, continuous monitoring of ventitatory function and transesophageal echocardiography of the right heart. results in situations ( patients, age days- , years), ino was applied - h postoperatively. oxygenation was improved in situations from _+ to + mmhg pc ; pulmonary pressure was reduced in situations from -* % to _+ % of systemic pressure. in situations, no reduction of pulmonary pressure was present, but measurement of cardiac output or echocardiographic analysis indicated an improvement of right ventricular function (right ventricular stroke volume + -* %, cardiac output + -* %). in situations (immediately postoperativ with suprasystemic pulmonary artery pressures [n= ], multi-organ-failure [n= ]), no response to ino could be determined. conclusions for a special group of patients, the selective reduction of pulmonary vascular resistance by ino has become an important part of postoperative therapy. using this selective afterload reduction, postoperatively depressed right ventricular function can be improved. this effect of ino seems to be the most important one in the postoperative period. thus, ino appears justified to be appfleo when impaired right ventdcular function could be improved even when pulmonary artery pressure is not raised or remains unchanged. obiectives : premature infant are exposed to danger of apaea due to anaesthesia during their tirst months of life. it is yet unknown whether prematurity is corelated to any other kind of reslgratory disorder due to anaesthesia within the tirst year of life. methods : we theretbre researched retrospectively for respiratory disorders in all infants under months of life belonging to asa group . they all had been anaesthetised in . in our clinic for the following surgical reasons: ingvinal haemia, umbilical haemia, hydrocelae testis and phymosis. results : in cases we tbund: lafingospasm during induction in anaesthesia ( , %), bronchospasm during induction in anaesthesia ( , %), impaired intubation ( , ~ postanaesthetic laringospasm ( , %), supposed aspiration ( , %),postanaesthetic inspiratory stridor ( , %), postinductional inngoedema ( , %), death after months in consequative of infection pneumonie ( , %), none of these disorders was correlated the prematurity, infants suffered of post anaesthetic apnea, of them had premature medical history. concludions : prematurity does not enhance the risk of respiratory disorders due to anaesthesia within the first year of life, except the danger of postanaesthetic almea needs spetial cosideration. it could be demonstrated that aepgi lowers pulmonary vascular resistance and indirectly improves cardiac function. this effect seemed to be selective, and was comparable to ino in the doses we have examined. therefore, aepgi could represent a clinically useful alternate to inc. however, further research is necessary to work up the benefits of either therapeutic strategy. objectives: heat and moisture exchange filtem (hme) are used as artificial noses for intubated patients to prevent tracheo-bronchial or pulmonary damage resulting from dry and cold inspired gases. furthermore they are used for the prevention of bacterial contamination of the anesthetic apparatus by the patient's exspired air. so they are considered as a time-and money-saving device in anesthesia. filters are mounted directly on the tracheal tube, where they collect a large fraction of the heat and moisture of the exspired air, adding this to the subsequent inspired breath. the effective performance depends on the water-and bacteria-retention capacity of the filter. this study evaluates the efficiency of four different filters under clinical conditions. methods: four different types of filters ( dar hygrobac, gibeck humidvent, medisize hygrevent and pall bb ) were investigated dudng mechanical ventilation over a pedod of hours. minipigs with hemorrhagic shock were intubated and ventilated for days in an animal intensive care unit (icu). after hours of mechanical ventilation the filter was randomly replaced maintaining the individual ventilatory conditions. the weight of the filter was determined before use and after removal after hours. the airway pressure was monitored online to record changes during use. tracheal secretions and both sides of the filter were microbiolologically tested to see whether bacteria of the animal's respiratory system could be found on the patient's side of the filter or if they even would have penetrated the barrier. results and discussion: over a pedod of hours of types of filters showed an increase in weight of + % and airway pressure. bactedal celonisation ccured in nearly all fillers ( of ) on the patient's side, whereas only three of four types of filters showed identical bacterial colonisation on both sides. the only filter that did not show bacterial penetration, increase in weight or airway pressure was the pall-hme, a condensation humidifier without hygroscopic salts for moisture retention. with respect to our data one should use a condensation humidifier if airway conditions should remain stable dudng mechanical ventilation and desinfection of the anesthetic apparatus should be avoided after each patient. aim: to assess the clinical uses of, and experiences with, the hayek oscillator. this is a non-invasive device capable ef delivering not only continuous negative pressure (cnp) but also external oscillatory ventilation around a negative baseline (eov-nb) using an external cuirass. this type of ventilation avoids the need for intubation and intermittent positive pressure ventilation (ippv) and facilitates weaning in ventilator dependent patients. patients and methods: patients in respiratory failure, age range weeks to years in a total of patient episodes were treated using either cnp or eov-nb mode. duration of treatment varied from hours to days. indications for use ef the device were: ) to facilitate weaning from ippv ) prevent reintubation of patients following unsuccessful extubation, and ) avoid intubation and ippv altogether using the hayek oscillator as the on[y means of respiratory support. results: there was an increase in pao :fio ratio after cnp and eov-nb (p < . , and p= . respectively, wilcoxon signed rank test). patients who were in respiratory failure with hypercapnia showed a statistically significant reduction in paco both with eov-nb and cnp (p= . and p= . respectively) but the magnitude of change was individually greater in the patients who were treated with eov-nb. all patients, however, showed a fall in respiratory rate (p< . ) after the application of the cuirass in cnp mode. there was no physiological deterioration related to the application of external extrathoracic negative pressure in either cnp or eov-nb modes. conclusion: the improvement in pao :fio , the fall in paco and respiratory rate were indicators of an improvement in ventilation. the proposed mechanisms include improvement in frc, recruitment of additional alveolar units, and improvement in secretion clearance resulting in reduction in the work of breathing. meek to ~ month of the lifo,the bemodyuanicfacls were defined uitb the help of tetropolar reography method!. the excretion of !he catbocholauines fcfi] mith the urine gas detertend by taylor ll,laoorsy ~ iacg/dayl. hsaltl in the hypercuagulation stage of bic we deflorteeed the acliuutiun of the tbrubio and plasiin syaet~ mitb the increase of the inhihitnrs, in this case we registered in full uahe dot this process coabined uitb the dayl~ excreliou with lho urine epinopbr ne e], nor~pinopbr no tel and dophanine io], lbat shod the inlensificatiou of the s~nthosis prnoe-s~es and the release of ea in blood fron hissue deport the actffat on of the svnpathadrenui systen ]sfisl assisted to furl the b?perd~nanical rosins of the eircuidion and increase the ,icrocirculatinn, the klinicai sings of the insufissieutly of the circulalion have not defined,that has been associated the conpensatury character uf the ehan~es of ~ and heludy~enic status, t~e uun~u|p-lion ceugulupatby bus been donoustraled in the hypocougulatien stage ~bat man xauifosted b the exhaust of lhe confulalion nod oessel-platel heuostasis, the consuxptton of cnnpononts tbronbln ,plnstin, kallek~eiu-kinln s~slots and the forniration eat in fell canoe clot uas accoqaued bs docrea,e of fl,nfl,o, the products of the xotabolisx of c~ and the activation of xonoaninoxydasu. the decrease of the extoll'on g and the exhaust deport co indicahd about t!e ]ou fund/anal reserve of ~fl~. it was one of the lain reason of ~bo heiod~uanic disbroed iheat insnfissient]~] and the uicrncireulaflion lintestinal codeme with the low effectife periferal flow] and nul[iplay organ failure,the distrued deport of sos mitb throubocytupenin no; be one of the nechanisn the dislrood of uessej-plalol heioshasis, the correlation bolueeo changes of boiostosis c~ and circulation ore reguired aduinistration nedidns, thai reslore the love s of c~ in the blood, prevent uulliplay organ failure and hetorrnge in children with sepsis, ~b~ectives: multi-measured correlative analysis of the most number of non-invasive indices of the cardiorespiratory system function was made to determine the structure of their interrelation and the ways of their adequate and effective correction. hethods: spiremetry, capno~raphy, oxygenography, indirect fick method at recurrent respiration, plethysmography, integral rheography -in all indices were used. the received data were processed on a computer by a standard package of statistical bmdp programs. results: women with ~h-gestosis (i group) and somatically healthy pregnant women (ii group) were studied. cluster analysis has shown that the rate of the mean correlation connection between ventilation indices was % in the ist group and % in the iind group; gaseous metabolism - % and %, respectively; central hemodynamics was ~ in both groups. conclusion: cluster interpretation allowed to suggest that an increase of the rate of the mean correlation connection between the indices was characteristic of effective adaptation as the system was multi-component and well-regulated. on the contrary, the increase of the rate of strong correlation connection between the indices reveals the rigidity of the system and the tensity of adaptation mschaniams, i.e. the proximity to decompensation. it follows from this that in cases of eph-gestgsis, the reliability of regulating ventilation and gaseous metabolism decreases. seve/e hypoxemia in non intubated patients represents a major contraindicafion to fiberoptic bronehoscopy (fob) and bronehoalveolar levage (bal), but these procedures are often required for a correct diagnosis of the causative agent of pneumonia. aim of this investigation was to veaify the safety and efficacy of bronehoseopic procedures during pressure support ventilation administered through facial mask (fm-psv). five intensive care patients, all immunoeompromised, ( males and females; mean age . • were enrolled in the study. all patients presented criteria for pneumonia with pao /fio ratio ~ and were responders to fm-psv. fob and bal were performed afte~ topical anesthesia with fm-psv ( ps = em h ; peep = emh ; trigger = -lemh ) continuously admires" tered ( ' before fob fio = . ; during fob, fio = and for ' alter fob, fio = . ). pao /fio ratio as well as saturation (sat) did not show signifteative changes during the procodure (fig.l) . no complication was observed and hemodynamic conditions were stable for all patients. cmv, pnenmoeystiis ( ), legionella and mycobaetermm tuberculosis were identified from bal allowmg a prompt and targeted therapy. we concluded that mask psv can represent an excellea~ technique to pexform fob and bal in severely hypoxemic patients without deterioration of gas exchanges and avoiding endotraoheal intubation. intensive care unit, hospital general of albacete, albacet~ spain. objective: to analyze the current incidence and epidemiology of total parenteral nutrition (tpn) among critically ill patients placed on mechanical ventilation. design: prospective observational study. setting: medical intensive care unit in a tertiary hospital. patients: a total of consecutive l'ritically ill patients with non-coronary related disease needing mechanical ventilation admitted in our icu during a months period. measurements: data of sex, age, diagnosis, and outcome were recorded. severity of illness and therapeutic effort in the first hours were measured using acute physiology score and chronic health evaluation (apache ii) and therapeutic intervention scoring system (ties). r~ults: mechanically ventilated patients, male and female, were studied. only ten patients needed tpn and their main diagnoses were: five cases of multiple organ failure secondary to pneumonia ( ), ards ( ) and septic shock ( ); two eases of acute panereatitis; and one mesenteric throngmsis, one status epilepticas, and one ,prolonged cholinergic crisis b~ suicidal organophnsphate insecticide subcutaneous injection. no statistically significant differences between both tpn and non-tpn groups were found: objectives: evaluate the efficacy of prone position in ards and determine its importance in the therapeutic algorithm. methods: consecutive patients with severe ards (murray-score > , ; pao / fit < mmhg; male, female, mean age years) were conventionally ventilated (pcv, peep - mbar, i:e=i:i, ppeak < mbar). if after hours pulmonary function did not improve patients were placed in prone position. change from prone to supine position was done every hours. beside ultimate survival, parameters investigated were aado , pao /fio , and venous admixture (qs/qt). results: during the first hours in prone position of patients showed a significant decrease in qs/qt ( . % vs. . %) and aado ( vs. mmhg), and an increase in pao /fio ( vs. mmttg). changes were most pronounced in patients with high qs/qt, and in patients with an onset of ards less than hours before first application of prone position. after an average of position changes ( to ) of patients could be weaned from the ventilator. patient could leave tile hospital. i the later course letality was primarily determined by additional organ failures and by the severity of the underlying disease. negative side effects were minor, including slight cardio-vascular depression and increase in p~co , and never posed a limitation to continuation of prone position. especially in patients with septic shock skin lesions in exposed areas could not always be prevented, prone position could easily be combined with all ventilation modes and with all intensive care interventions. also immediately after major surgery and in patients with open packing prone position was possible. conclusions: in this investigation prone position proved to be an efficient and safe method in the treatment of severe ards. patients with a pronounced ventilation/ perfusion mismatch and patients in the early stages of ards appear to profit most from prone position. though the immediate effect on oxygenation is striking, still more the % of all patients die from multi organ failure and underlying diseases. a proposed therapeutic algorithm for ards is as follows: if under conservative ventilation (pcv, peep < mbar, ppeak < mbar) pulmonary function does not improve within - hours prone position should be applied. when after - position changes no lasting effect can be achieved further ventilation modes (e.g. pc-irv, aprv, no, etc.) should be used in addition to prone position. standard intensive care principles, such as fluid restriction and optimization of circulation, apply also to patients in prone position. objectives: nitric oxide reacts with superoxide to form peroxynitrite, an extremely reactive and toxic species. we quantified the presence nitrotyrosine, the stable product of the interaction ' of peroxynitrite with tyrosine residues in the lungs of pediatric patients that died with respiratory distress syndrome (rds). methods: paraffin embedded lung sections, obtained at autopsy, were incubated with a polyclonal antibody raised against nitretyrosine, followed by a secondary fluorescent antibody. alveolar structure-associated fluorescence was quantified using existing methods. results: tissue sections from patients who died with rds exhibited significant specific immunostaining which was uniformly distributed across the blood-gas barrier. in contrast only background levels of fluorescence were seen in the lungs of patients who died from non-pulmonary causes. intense staining was also seen in the lungs of rats that breathed % for h, a condition known to result in rds-type illness; no immunostaining was observed in air-breathing rats. conclusions: significant levels of peroxynitrite may be formed in the lungs of patients with acute lung injury. peroxynitrite may be contributing to the pathology of rds by damaging key components of the alveolar epithelium including the pulmonary surfactant system. mechanical ventilation time was prolonged ,g • days in patients with ardsvs , _+ l, days in control . mean staylcuwas lg _+ ,g days in the ards group vs , • , days in control group postoperative mortality rate was % in ards patients vs , % in those without respiratory failure. -ards incidence in liver transplantation is low ( , % in our sene) but it causes high mortality ( %) page, gas ventilation of the perfluorocarbon-f'dled lung, supports gas exchange and circulation in small animals (< kg) with lung disease. we hypothesized that large animals could be supported by page without adverse effects on bemodynamics. we first elucidated the determinants of gas exchange in normal sheep, and applied them to a model of adult respkatory distress syndrome (ards). methods: using the ventilator settings determined to be optimal in our pilot study (fio of . , peep of cm h , imv of bpm, it of %, and tv of ml/kg), sheep weighing . ~ . ) kg had lung injury induced by instilling ml/kg of . n hc into the trachea. ten minutes after injury, sheep with pao < ton" were randomized to continue gas ventilation (control, n= ) or to institute page (n= ). page was instituted by instilling . l of unoxygenated pefflubron into the trachea and resuming gas ventilation at the previous settings. abg's were drawn at baseline, minutes after injury, minutes after injury, and then every minutes for hours. objectives: inhaled nitric oxide (no) can improve oxygenation and decrease mean pulmonary artery pressure (papm) in hypoxemic patients with ards. in severe hypoxemic copd patients, it is not known whether inhaled no can exert a similar effect on hemodynamics and gas exchange. therefore, we investigated die response of inhaled no in hypoxemic copd patients and the results compared with those obtained in a group of ards patients. methods: ten copd patients (age _+ y;fev~ . _+ . l) and ards patients (age _+ ; lis . _+ . ) mechanically ventilated were studied. hemodynamic parameters were measured using a swan ganz catheter. arterial and mixed venous blood gas determinations, sao , svo , hb and methb were measured (abl ,osm ). mean intratracheal concentrations of no and no were continuously monitored using a chemiluminescence analyzer (nox ) . during the study the ventilatory pattern and fioz were kept constant. the protocol was for ards group: basalt, no loppm, basal~; copd group: basalz, no lo ppm, no ppm, no ppm and basal . after a steady state of rain hemodynamic and gas exchange measurements were performed. a positive noresponse was defined as a % increment in pao . results: papm was similar in both groups and decreased significantly after no (ards, basal . _+ . mmhg, no . + . mmhg, p < . ) (copd, basal . _+ . mmhg, no- . _+ . nrmhg, p< . ). all other hemodynamic variables remained unchanged after no. basal oxygenation was higher in copd group (paojfio _+ mmhg) vs ards group (paojfio _+ mmhg)(p< . ). after no- , pao increased ( _+ mmhg to _+ mmhg, p< . ) and qs/qt decreased ( + % to _+ %, p< . ) only in ards group. in both groups, significant correlations between basal papm and inhaled no-induced decrease in papm were found. inhaled no-induced increase in pao /fio was not correlated with basal paoflfio . no responders were / ( %) in ards group and / ( %) in copd group (p< . ). conclusions. in hypoxemic ards and copd patients, inhaled no decreased mean pulmonary artery pressure. however, oxygenation only ameliorated in ards group because die number of responders to inhaled no were higher in ards group and this effect seems not to be related to the basal hypoxemia. these results might be explained by the v/q abnormalities present in copd patients. grant fis / . objectives: it has been recently reported that expired con slope as a function of time is modulated by total respiratory system resistance (rrs) in critically ill patients (chest ; : - ) . in this study, we analyze the relative contribution of disease (dis), endotracheal tube resistance (rtube), airway resistance (rmin), additional resistance (~rrs), autopeep (peepi) and dylmmic/static elastance (ed/es) to the co elimination in different clinical conditions. methods: we have studied adult patients ( controls, acute respiratory failure, severe ards and copd) mechalfically ventilated (servo and c, siemens) without peep. we recorded tracheal pressure, airflow and capnograms. signals were analogic to digital converted for posterior data analysis. objectives: alveolar ejection volume (van) can be defined as the fraction of tidal volume (vt) with minimal dead space (vd) contamination. according to the classical paradigm: limvd_~ [vco /vt] =facoz, vco vs vt relationship tends asyntotically to a constant slope when approaches end-tidal volume. we have defined van as the volume that defines this relationship until a limit of % variation. methods: six subjects with normal respiratory mechanics were studied during anesthesia for minor surgery. two subjects, otherwise normals but having high values of total resistance and dynamic compliance, were also studied. capnograms were recorded in steady-state at levels of vt ( . , . and . l) and four levels of peep ( , , and cmh objectives: patients with ards presented lung abnormalities which originate an increase in airway resistance (rmin), in additional resistance (~rrs) and in static elastance (ers). application of peep further increases ~rrs. capnographic indexes reflect lung ventilation]per fusion inhomogeneities. in these conditions, the effects of peep on lung mechanics could be better understood by simultaneous measurement of capnographic indexes. methods: we studied groups of subjects. n: normal subjects scheduled for minor surgery; arf: critically ill patients with mild acute respiratory failure; ards: patients with early ards (< h). we recorded tracheal pressure, airflow and capnograms. signals were analogic to digital converted for posterior data analysis. respiratory system mechanics was assessed by constant end-inspiratory and end-expiratory occlusions technique. at equal tidal volmne ( . l) a peep level of , , and cmh was applied in all patients. we calculated ers (cmh /l), rmin, c~rrs (cmh /l/s) and autopeep. capnographic indexes were alveolar ejection volume (vae)/vt ratio and expired co slope beyond vae (sipco in contrast to synthetic surfactant natural suffactants (alveofact| are able to inhibit pmn-activation. after incubation of activated neutrophils with surfactant, l-selectin expression is decreased. these effects depends on which preparation is used. we conclude, that natural surfactant (aveofact| can perhaps influence early recruitment (,,rolling") of pmn in patients with respiratory failure like ards. with ards hormann cb, baum m, putensen c, knapp r, lingnau w, putz g . clinic for anesthesia and general lntensiv care medicine, university of lnnsbruck, anichstrabe , innsbruck objectives: in thoracic ct scans of patients with severe ards atelectasis and pleural effusion can be found in the dependent lung regions. by rotating these patients from left lateral position to right lateral position a redistribution of the ct densities, a recruitment of atelectasis and therefore an improvement of gasexchange is possible within a few days ( , ). the objective of this study was to find out the mechanism of alveolar recruitment during lateral positioning by ct scanning in left and right lateral position. methodes: after approvel by the local institutional reviewboard we investigated ventilated patients with severe ards (entry criterias: murray score > , ) in the ct scann of the university hospital. after a stabilisation period of minutes in supine position a thoracic ct scan slice cm above diaphragm was taken. then two different positions of the patients were studied in a randomized order: a) degree of left lateral position, b) degree of right lateral position. each lateral position was held for minutes. at the end of each of these periods a thoracic ct scan slice cm above diaphragm was taken. quantitative analysis of ct scan data was based on the frequency distribution of the ct numbers. to quantify the alveolar recruitment during lateral positioning by means of ct scan we defined compartments within the lungs: a) normaly inflated lung, b) poorly inflated lung, c) noninflated lung ( = atelectases) ( ). results: independant of the side of lateral positioning (l) in the non-dependent upper lung a significant increase of the normaly inflated compartment (s: %; l: %) as well as a significant decrease of the noninflated compartment (s: %, l: %) was observed in comparison to supine position (s). in the dependant lower lung the normaly inflated compartment decreased significantly (s: %, l: %) whereas the noninflated compartment increased significantly (s: %, l: %). throughout the whole studyperiode we did not observe any significant change regarding gasexchange and hemodynamic parameters. conclusions: in lateral position the non-dependent upper lung is decompressed. therefore a significant recruitment of atelectases is observed in the upper lung within minutes. on the other hand the dependent lung is compressed by the weight of the upper lung and the mediastinum. a great amount of the alveoli of the dependant lung collapse in this short time intervall. therefore the net effect of recruitment of one positioning maneuver is very small. when positioning patients one should be aware, that the patient is kept in each lateral position long enough to clean up the atelectases in the non-dependant lung and short enough to compress less lung tissue in the dependant lung. objective: to analyze effects of low-dose no inhalation ia patients with severe aeut~ respiratory distress syndrome (ards) over five days. methods: we prospectively studied patients ( men, woman) with severe ards admitted to our icu between may and may who required no inhalation with a dose of ppm for at least days. entry criteria for no injaalafioa were murray score >i . aud pat/fie < nun hg with peep >~ em i~o for at least hours. all patients were sedated, intubated and mechanicauy vantil~ed with volume assist-control ventilation, and had indwelling arterial catheters (pulmonary artery, and radial or femoral artery) to measure cardiac output (by thermodilufion) and relevant intravaseular pressures, and to calculate derived parameters. no was administered between y piece of the ventilator and endotraeheal tube and flow was adjusted to obtain ppm no in the inhaled gas. the no, no and no x concentrations were continuously measured at the distal end of the endouacheal tube by the chemiluminiscence method (nox , see-seres, france). metahemoglobinemia levels were mesured daily. no inhalation was manteined if paojfio ~ improved at least % and was stopped when the change in pao /fio ~ was below % or when the patient presented a paojf > mm hg a~er minutes without no inhalation. every day we made an on-off test to determine if no inhalation improved pao /fio ~. statistics: analysis of vmiance. data: mean + standard deviation. results: the mean age was . +_ . years and mean lung injury score was . • . . mortality was % ( / ), metahemoglobinemia . • . %, and no concentrations zero. paojf~o always improved significantly al~er ppm no inhalation (see :~ conclusions: reintubation in salf-extubated patients strongly depends on the type of meehamcal venfilatory support: the probability of needing a reintabation ff ese occurs during fult vontilatory support is higher than ff ese occurs during weaning. these data suggest that some patients may remain under weaning from mechanical ventilation for unnecessarily prolonged periods of time. objective: the aim of this study was to evaluate the acute effects on gas exehonge and hemodynamics due to positional changes from supine (sp) to prone (pp) in patients with severe acute respiratory distress syndrome (ards). methods: nine intubated, sedated, paralyzed and mechanically ventilated patients with severe ards were prospectively studied. all had a murray score > . , and a pao /f~o < with peep ~ cm h for at least h. all patients had indwelling arterial catheters in the pulmonary artery as well as in the radial or femoral artery in order to measure cardiac output (by thermodilution) mad relevont pressures, and to withdraw blood samples. arterial blood gases and hemodynamie parameters were measured first in sp, and then in pp after minutes of stabilization. vontilatoly parameters remaing unchanged during all the study. statistical analysis was done by the non parametric wdeoxon test. data are expressed as mean ~= sd. results: there were men and women with a mean age of . years ( - ) and mortality was % ( / ). main results are shown below: objective: to describe and compare a new method for obtaining p-v loops (p-vcv) by using a two-way collins valve (twv) with thosu obtained by the supersyringe method (p-vss). methodology: we prospectively studied patients who had an aeute lung injury and were intubated, sedated and paralyzed, and mechanieany ventilated. we performed the p-vev loops and p-vss loops in random order, and the static inflation pressure was limited to emh with both methods. pressure (p) was measured at the airway opening by means of a differential p transducer, and volume was obtained from flow (measured with a pneumotacograph) integration. the p-vse method has already been described (h~trf a,et al.bepr ; : - ) . the p-vev method consists in the following: the inlet of a twv is connected to the ventilator's y-piece, and both outlets are couneeted to the endotraeheal tube by means of an additional y-piece; one of this outlets has a one-way rudolph valve in order to allow inspiration but not expiration during the inflation maneuver. changing the twv tap position allows basal ventilation or progressiveinflation of the respiratory system. this maneuver is as follows: during an end-expiratory occlusion, the ventilatory settings are adjusted to deliver a ml v r with a respiratory rate of /min and i/e ratio : ; at the same time the twv tap is ehonged in order to divert flow through the one-way valve. inflation then begins alter releasing the expiratory oonlusion. pressure and flow signals were digitized and acquired by a computer for subsequent data analysis. we analyzed the following parameters: inflation compllonee ( objective: to analyze the variables which eventually may differentiate ards patients who do and do not respond to low doses of inhaled no. we prospectively studied patients ( men, woman) with severe ards admitted to our icu between may and may who were treated with no ( ppm). the onta'y criteria for no inhalation were murray score >/ . and paojfo z < mm fig and peep >/ cm i~o for at least hours. all patients were sedated, intubated and mechanically ventilated with volume assist-control ventilation. tidal volume was between and ml&g, with constant inspiratory flow, respiratory rate was - /rain, and i/e ratio between : to : . all patients had indwelling arterial catheters (pulmonary artery, and radial or femoral artery) in order to measure cardiac output (by thermodiintion) and relevant intravascular pressures, and to calculate derived parameters. no was administered between y piece of the ventilator and ondotracheal tube, and flow was adjusted to obi~a ppm no in the inhaled gas. the no, no and no x concentrations were continuously measured at the distal end of the endotracheal tube by the chemilumiinscenee method (nox , see-seres, france). metahemogtobinemia levels were measured daily. we considered a response to no inhalation when an improvement in paoz/fo above % was observed after the inhalation of ppm no (group r) . when the cha~age in paojfi z was below % it was considered a lack of response (group non-r small airways functional abnormalities have been recognized as a common feature of lung pathology. however peripheral airways contribute relatively little (~ %) resistance to flow and there disturbances can not be adequately estimated by conventional measurements of respiratory mechanics. the purpose of the study was to evaluate the relationship between raw and small airways conductance following weaning from ventilator methods. patients (age: - years; males) with no serious complications al~er mitral or multiple valves replacements and with more than hrs on mechanical ventilation have been enrolled in this study. the modified flow interrupter technique (ptg "gould" with fleish head # ; differential pressure transducer pm- -tc "statham" w amplifier "kistler ") and flow-volume recording of forced expiration (fleish head # ) have been applied before surgery and following operation on mechanical ventilation (my), after extubation (t:xtijb), on ( nay) and ( day) days. airways specific conductance (sg aw) has been calculated as a mean of - consequent measurements in each patient at each stage. the sac was estimated by max expiratory flow at and % of vc on - f-v curves (mef .~ , mef ) all the data were statistically analyzed with t-test introduction : noninvasive ventilation (niv) reduces the need for endotracheal intubation, the length of stay in icu and the mortality rate in acute exacerbation of copd. however, some patients failed to be ventilated with niv. .objectives...; to further delineate patients who failed to be ventilated with niv and to obtain predicted factors of failure. patients : a cohort of patients ( • years) presenting with acute exacerbation of copd (fevi: • ml, paco : • , ph: . • . ) and nonmvasively ventilated (pressure support through a full-face mask) between april and may twenty-seven ( %) were successfully ventilated with niv (discharged alive without the need for endotracheal intubation) while ( %) failed, requiring endotracheal intubation. .methods : patients successfully ventilated and those who failed were compared according to respiratory and nonrespiratory variables univariate analysis (wilcoxon rank-sum test and fisher-exact test) was performed to select variables included in a multivariate analysis by stepwise logistic regression. results : underlying disease assessed by the simplified acute physiologic score ( • vs • , p = . ), creatinine serum concentration ( • vs • gm/l, p = . ), blood urea nitrogen (bun : • vs mm/l, p = . ), age ( • vs • , p = . ) were higher and encephalopathy ( vs %, p = . ) more frequent in patients who failed. multivariate analysis showed that encephalopathic patients (or (odd ratio) = , p = . ) older than years (or = , p = . ) and presenting with bun >_ mmyl (or = , p = . ) failed to be ventilated with niv. variables related to the respiratory" status (i.e. paco , pao , fev ) were unable to predict tile failure of niv. conclusion : copd patients older than years, presenting with acute exacerbation, encephalopathy and bun > ram/l, should be carefully monitored because of high probability of failure with niv. methods:from february to december we studied pa_ timnts, males and females(mean age +/- ); of the se had emphysema,lo chronic bronchitis, dilatative car diomyopatia,with tracheostomy and emphysema.mean pac at admission in icu was +/- mmhg,while when weaningbegan, +/- .mean autopeep was cmh ( - ).all patients were ventilated in crpv as long as four hours to calculate st tic and dynamic cmpliance and autopeep.then the ventila tion was continued with psv+cpap(peep cmh objectives: analysis of the incidence of neurogenic pulmonary edema (npe) in a population of headtrauma patients with acute respiratory failure (arf). npe can occur after a central nervous system insult. differential diagnosis: cardiogenic pulmonary edema and other forms of non eardiogenic pulmonary edema. true incidence and pathophysiohigy remain poorly defined, however the role of catecholamines seems undeniable. early onset npe (within h after trauma) is characterised by hypoxemia, transient pulmonary hypertension and bilateral central fluffy infiltrates on chestx-ray. characteristics of cardiogenic edema or pneumonia are absent. late onset npe, (beyond hours after trauma), is more insidious. the clinical and radiographic picture has to clear within to hours. ( ) methods: all headtrauma patients admitted from january to december , in a nearotrauma icu setting were retrospectively analyzed for arf with as sole criterinm a pao -fio ratio < . results: neurotrauma patients were admitted during . patients ( %) presented with severe head injury (gcs< ), patients ( . %) with moderate (gcs - ) and patients ( . %) with minor head injury (gcs - ). overall mortulity was . % early (within h. after trauma) and delayed onset respiratory incidents were distinguished, counting for ( . %), respectively patients ( . %), patients ( . %) had early and late respiratory complications. early respiratory insufficiency was caused in patients ( . %) by aspiration, in patients ( . %) by lung contusion, in patient ( . %) by fat embolism and in patients ( %) by npe. in the late onset group patients ( . %) presented with pneumonia, ( . %) with fat embolism and ( . %) with npe. the npe group, patients, presented as follows: patients ( . %) developed early npe, and ( . %) delayed onset npe. patients ( %) died within the first days after admission, showing high mortality. gcs was less than in patients ( . %), indicating severity of head injuries. conclusions: high incidence of arf with various etiology ( , ~ was found in this population. in about % of all admitted hcadtrauma patients ( , % of arf) npe was causing attetial hypoxemia. occurrence of npe seems to be related to the severity of the brain injury and thus to outcome. these data call for extreme vigilance in respect of the insidious occurrence of npe. were included if recovering from respiratory failure and if in the opinion of the primary physician were ready for extubation. patients were excluded if undergoing compassionate withdrawal of support or had tracheostomies. the attending physicians were blinded to the measurements. included patients were placed on pressure support (ps) of em h with demand-flow continuous positive airway pressure (cpap) cm h . after a minimum of minutes on the above sehiogs: gastric intramucosai pc'o , abg, and a p . were measured. the padents were then disconnected from the ventilator for a period of one minute and the patients" respiratory rate and minute ventilation were measured using a wrights respirometer to calculate the frequency to tidal volume ratio (f/vt). patients were then extubated. extubafion failure was defined as the inability to maintain spontaneous ventilation for hours for any reason. results: twenty patients met criteria and were studied over one month period in october . six of the twenty patients ( %) failed weaning. the mean and standard deviation is outlined in failure . +/- . . +/- . . +/- . . +/- . comparison between roc areas shows phi and p . to each show a statistically significant difference from an area of . (p<o. ). the area at which the test has no discriminative value. this is not the case for either the integrative index or the f/vt ratio. the differences between areas for each curve is not statistically significant. the area's for each roc curve is shown in table #' . results. of the newborns referred to us for ecmo-therapy developed barotrauma, of the required ecmo and one of the three other patients who did not recieve ecmo-therapy died. to determine the correlation between the risk factor barotrauma and the severity of the pulmonary situation, we determined the oxygenation index of each patient referred to us for ecmo-therapy . the table demonstrates , d- giessen, frg. inhalation of nitric oxide (no) and aerosulizatiun of prostaglandin (pg) i: have been suggested to achieve selective pulmonary vasodilation and improvement of arterial oxygenation in patients with acute respiratory distress syndrome (ards). we directly compared these two modes of transbronchial vasodilator therapy in ards patients mechanically ventilated for - h (mean murray lung injury score [ ] . + . ). patients were randomized to receive either first no and then pgi (n= ), or vice versa (n= ), with an intermediate baseline period. each drug was titrated individually to find the lowest effective dose for maximum improvement of arterial oxygenation. gas exchange variables, including data from the multiple inert gas elimination technique (miget), and hemodymmaics under application of no/pgi were compared to pro-and past-challenge values. no (mean dose . + . ppm) increased the mean oxygenation index (pao /fio ) from + to + mmi-ig (p < . ) and reduced the shunt-flow from . + . to . : . % (p < . ). aernselized pgi (mean dose . + . " ng/kg rain) augmented pao /fio from + to + mmhg (p < . ), and decreased shunt from . + . to . + . % (p < . ). the miget analysis showed predominant redistribution of blood-flow from shunt areas to regions with normal ventilation-perfusion ratios in response to both agents. in patients, both no and pgi caused an increase in pao /fio by at least rnmhg. two further patients displayed a corresponding improvement of arterial oxygenation in response to either no or pgiz. the mean pulmonary artery pressure decreased from . : . to . : . mmhg in response to no, and from . : . to . : . mmhg (p < . ) in response to pgi . cardiac output, systemic arterial pressure, and right and left heart filling pressures were not affected by either agent. we r that individually titrated doses of inhaled no and aerosolized pgi~ effect selective pulmonary vasodilation and redistribute blood-flow from shunt-areas to weu-ventilated regions with nearly identical efficacy profiles. obieetives: the use of extraeorporeal bypass systems for oxygenation and co -removal is performed in patients with acute respiratory distress syndrome (ards) to reduce mortality and to improve restitution of pulmonary functions. high-dose heparin -commonly used in such patients to prevent thrombotic complications -might cause incurable bleadings as a major risk. this lead to the development of heparinized bypass systems; results of animal and first clinical studies proposed that such systems might run with low-dose heparin or even without any systemic anticoagulation. methods: since , patients with severe ards were treated with extracorporeal lung assist (ela) using heparin-coated systems (type maxima, medtronic, carmeda coating) in our icu. they received a moderate systemic heparinization. standard clotting assays (act, aptt, tt, ptt, at-ill, fbg, fsp) as well as special tests (tat, r~-tg, pf , pal-l, d-dimers, protein c, cl-inhibitor) were performed. results: covalent heparin-eoating of the ela-systems combined with lowdose heparinization could not prevent major changes in coagulation: ) in mean, platelets dropped from /nl to /nl within h after onset of ela. ) tat levels were already elevated before ela start ( ug/]) and demonstrated an additional peak h after onset of ela (up to ug/[). ) in parallel, there was a transient peak of pai-i levels (from to au/ml} h after onset of ela. ) in mean, fibrinogen levels dropped from to mg/ ml within h after onset of ela. ) in mean, cl-inhibitor levels dropped significantly from % to % after onset of ela and reached the initial levels within h. ) after membrane change, there were significant changes for c -inhibitor, fibrin-d-dimers and tt. ) global clotting tests such as aptt, ptt and tt were within normal range. conclusions: patients with severe ards develop a prethrombotic state already before they get connected to the ela bypass system. after onset of ela, they experience additional involvement of procoagulant, anticoagulant, fibrinolytic, and complement systems. in parallel to laboratory findings, clinical data suggest that the use of heparin-coated systems with accompanying systemic low-dose heparinization does not avoid thrombembolic and hemorrhagic complications in tong-term ela patients. thus, at the present, higher dosed individually adjusted heparin treatment has to be recommended. thereby, standard clotting monitoring is not sufficient. objective: poor muscle performance contributes to prolonged dependence on mechanical ventilation. longitudinal data on muscle function in icu patients is scarce. we evaluated changes in inspiratory and peripheral muscle performance during prolonged intensive care in patients with acute respiratory failure. methods: patients requiring intensive care for more than one week were studied. maximum inspiratory pressure (pimax) was measured twice a week for a maximum of three weeks. handgrip power (dynamometer) and subjective fatigue (keldet score) were obtained in survivors only. one measurement was done on the date of extubation. pimax pressure was obtained by occluding the airway for seconds or at least five inspiratory breath attempts. obiectives -measurement of peep-induced changes in lung volume helps to assess respiratory mechanics in acute lung injury (ali). we evaluated the accuracy and stability of a new respiratory inductive plethysmograph (rip), in the measurement of peep induced changes in end-expiratory lung volume (eelv) and tidal volume (vt) against volume reference, pneumotachograph (pnt), methods -two hours periods of basal ventilation and stepwise increases and reductions of peep ( - - - - cm h ) were recorded in patients with all. in addition, the new rip device (respitrace plus tm) was compared to an older rip (respigraph tm, nims, fl, usa) to determine its thermal stability using cold and warm devices and a ventilated lung model. results -the difference between the new rip and pnt in the measurement of vt was - _+ mi (x _+ se) or a - . _+ . % error. increasing peep from to cm h induced a + ml change in eelv. a difference of + ml ( . % of max. eelv change) (ns) was found between rip and pnt eelv readings. during controlled ventilation with constant settings the mean change in eelv was _+ ml/ min (fig.i) . validation of calibration showed a mean error of -+ . % after rain. the new rip had a higher drift when cold (cold + ml/ min vs warm _+ ml/ min), whereas the old rip was thermally stable (cold - + ml/ rain vs warm i + ml/ min). trauma icu, hospital traumatologia y rehabilitacidn. vall d'rebron. barcelona. spain. recent data suggest that the proportion of patients with relevant discrepancies between two jugular bulb (jb) oxygen saturation (sjo ) values is higher than suspected. objectives: determine the incidence, the significance and the pro nosis value of those differences,if they exist,in severe head injured-patients. material and methods: severe head-injured patients, coma glasgow scale (gcs) , with diffuse brain injury according to marshall criteria in the first ct scan, icp recorded, with an interval from accident-double jb monitoring < than hours, were studied. data from bilateral sjo were obtained simultaneously, every hours. discrepancies were considered significant, when differences in sjo were > %. no chan es in treatment protocol (hyperventilation, man• etc) were carried out due to this study. results: men and women were studied, aged • yrs. at arrival at hospital, gcs were < in and ) in to. the incidence of high icp() mmhg) were sz at the entry. the mean therapy index level required to control lop was ~l all patients required vasopressor therapy to maintain upp over ds mmhg. in patients a s.s f swan-ganz fiberoptic catheter was used to obtain a continuous recording of sjo . in the others , sj were intermittently controhed.the mean time of monitoring were d. • days. ten patients died within this period. a total of . blood samples were analized. at arrival, sjo discrepancies were found in patients, b %. at hours, the incidence were lower, / , . %. at th day, were h/ , z and at day , when the catheters were retired, ii[ , z showed discrepancies. the ct showed new injuries in g z of patients with differences > ~ in sd values throughout treatment period. none of those were considered for neurosurgical treatment. no correlation was found between iop and sjo values and sjo differences. conclusions: the incidence of discrepancies between sjo was higher than expected in severe head-injured patients. these situation could reflect disturbances between demands. when differences are known, and those lend to change, the ct scan, nearly always, will show new injuries. platelet-activating factor (paf) is an inflamatory mediator implicated in the pathogenesis of bronchial asthma and acute respiratory distress syndrome (ards). its inhalation in healthy subjects produces transient bronchoconstriction and mild ventilation-perfusion mismatch, together with peripheral leukopenia as a result of intrapulmonary neutrophil (pmn) sequestration. likewise our group has shown in healthy subjects and asthmatic patients that aaibutamol (s) inhibits both pulmonary and systemic effects of paf, suggesting that s may inhibit paf-induced venoconstriction in pulmonary microoirculation. the aim of the present study was to investigate if s inhalation decreases pmn by lung sequestration induced by paf. we studied healthy, non-atop• nonsmoking subjects ( m/ f, + yr), which were pre-treated with s ( ,ug) or placebo, with a randomized, double-blind, crossover, design, before paf ( ,ug) inhalation. we measured the respiratory system resistance (rrs) by forced oscillation, arterial btood gases and both total white cell and pmn count every min over a min. period. simultaneously, we recorded continuously the lung dynamics of inm-neutrophil and tc m-erythrocytes activity, with a gammacamara. after placebo, paf inhalation decreased white cells (from to x /l), and pmn(from to _+ x /l), and increased aapo (from . _+ . to . + . mmhg, p<o. ) and rrs(from . . to . . cmh .s.i q ) (p < . each). the fall in total white cell count correlated with the intrapulmonary pmn retention (r = . , p < . ). by contrast, after s, paf did not induce any change in white ceil count (from to + x /i), pmn count (from to x /i), aapo (from . to . + . mmhg), and rrs (from . . to . . cmh .s.i ). compared with placebo, after s there was a lower ~lln-pmn lung activity ( . . vs . . cts/mci/pixel, p<o. ), lower intrapulmonary pmn retention ( . . vs . . %, p=o, ), and a faster washout ( . . vs . . s ~, p= , ). our results indicate that s inhibits paf-induced intrapulmonary pmn sequestration, being consistent with the hypothesis that s may offset the venoconstriction of pulmonary microcirculadon caused by this mediator. supported inpiratory muscle fatigue with failure of force generation as def'med by a tensiontime index (tti)> . - . has been shown to occur in normal volunteers and in stable copd patients with a specific imposed breathing pattern. its role, however, in hypercapnic respiratory failure is less certain. we studied failed weaning trials in copd patients in which breathing pattern, tension-time index (tti) of inspimtory muscles, dynamic peepi, dynamic lung elastance, lung resistance, and arterial paco and ph were measured at the beginning and end of a t-piece weaning trial. in addition, the change in esophageal pressure during a mueller maneuver (apes max) was measured. a weaning trail has been prospectively defined to have failed if one of the following criteria was met: a rise in pco > mmhg from baseline accompanied by a fall in ph< . ; a respiratory frequency (f) > /min; excessive accessory inspiratory muscle recruitment; and a marked increase in dyspnea. values are expressed as mean • se. weaning failure was characterized by a more rapid, shallow breathing pattern, worsened mechanics, hypercapnia and respiratory acidemia despite an unchanged tri and pes max. we conclude that in this setting hypercapnic respiratory failure is not a consequence of inspiratory muscle fatigue. rather the adopted breathing strategy and resultant hypercapnia may represent an adaptation to forestall the onset of muscle fatigue. concerning the investigated elf-par~eters, no stadstically signhqcant differences were detected between the pgi and the control group. histopathologlcal changes occured in both groups and consisted in rare focal flaaaning f tracheal epithelium with loss of cilia and slight inflammatory cell infiltration, as well as slight swelling of alveolar typo pneumoeytes. sections of generation , and from bronchial tree were free of pathological changes. conclusion: alter h inhalation of p~ji no signs of respiratory-lract tissue damage caused by the aerosol could be detected. the minor pathological findings in the trachea are most likely due to mechanical irritation by bronchoscopy, changes of the alveolar epithelium are known for long-term mechanical ventilation . objectives: the aim of this study was to evaluate of efficiacy of ganglion stetlate blockade in patients with respiratory failure. methods: two groups of patients were investigated: group i (n = ) trauma patients with acute lung injury (ali), group if (n = ) patients with asthmatic status. in all cases continuous mandatory ventilation (cmv) was used with bennett ae. in both groups bilateral ganglion stellate blockade with antero-lateral approach was performed, using . % marcain. the following parameters were analysed: pao , sao , paco~, pip and c~t~t. results: in trauma patients with aij after bilateral ganglion stellate blockade short -lived and slight improvement of pao and sao , decrease of pacoz and pir and increase of static compliance of respiratory system were found. in second group bilateral ganglion stellate blockade interrupted the asthmatic status and significant statistical improvement of parameters of oxygenation, ventilation and respiratory system mechanics were observed. conclusions: we suggest that the bilateral ganglion stellate blockade is a very useful method in treatment of patients with obstructive respiratory insufficiency. the aim of the study was to analyse whether there exists serum and urine electrolyte disorder in patients(pts.) with acute respiratory insufficiency(ari). the study included t pts. with ari (pao : , @ , kpa. paco : , i- , kpa, ph: ~: , , hco : , :~ , mmol/ , sao : , ~- , %) who were hospitally treated due to pneumonia( pts.),emboly of the pulmonary artery( pts.) and severe attack of bronchial asthma ( pts). among tham there were ( , %) males and ( , %) females, average age , ~: , years, otherwise previously healthy. electrolyte concentracions were measured at the onset of the disease in serum and urine collected during hours (sodium-na,potassium-k, chlorine-c , calcium-ca,magnesium-mgand phosphorus-p). the measured serum and urine electrolyte concentrations were compared with respective referent values (rv). by serum electrolyte analysis, the following average velues were obtained: na:l o, the object of our investigation was a group of pts with massive pneumonias, males ( . %), females ( . %),mean age yrs.thirteen ( %) of them were smokers, ( %) nonsmokers. only pt ( . %) had pre-existing chronic respiratory disease, and ( . %) were admitted for the first lime,with no previous respiratory anamnesis. diagnose was based on anamnestic data of productive cough in pts( . %),physicaly ~onchial breathing in i~s ( . %),white cell count onder x /l in pts( . %). radiographicly, bilateral massive homogeneous shadows were found in pts ( . %), onilateral in pts( . %),pleural effusion in pts ( . %). abnormal renal function was found in pts ( . %). sputum culture was positive in pts ( %): slr.pneumoniae, str.pyogenes, pse'udomonas aerug, in , , cases respectively. all patients had remarcable hypoxernia (pao range from , to , kpa) without hypercalmea. all patients needed oxygenotherapy together with antibiotics and other .symptomatic therapy. nineteen pts had anaelioration of general condition and normalization of blood gas analyses, while pts with the lowest hypoxcmia died.in conclusion, massive pneumonias are frequently followed by respiratory insufficiency which is one of the markers of pneumonia severity. as existing hypoxemia complicates the course of the disease,prolonges the recovery, makes therapy more complexe and may be cause of death , frequent blood gas measurement is recomanded. we studied the effects of bosentan (bos), an eta and etb receptor antagonist, to examine if endogenous et mediates pulmonary hypertension in anesthetized and ventilated dogs with acute lung injury due to oleic acid (oa). the gradient between pulmonary artery pressure (ppa) and occluded ppa (ppao), and gas exchange (evaluated by arterial blood gases and sf intrapulmonary shunt) were measured at controlled flow. in dogs (treatment), data were collected at baseline, during long injury (obtained rain after intravenous administration of oa . ml/kg), and again after bos ( mg/kg intravenously). in dogs (pretreatment), data were obtained at baseline, after bos and then after oa. in treated dogs, oa increased (ppa-ppao, mmhg, table, means + sem, * p < . vs base) and deteriorated gas exchange. after oa, bos did not affect pulmonary vascular tone nor gas exchange. in pretreated dogs, bos had no effect on baseline pulmonary vascular tone but prevented the increase in (ppa-ppao) after oa. the deterioration in gas exchange after oa was not influenced by bos pretreatment. objectives: the alveolar tension is measured by the application of the alveolar air equation in which the arterial pco is used or by the simplified form of this equation in which the respiratory exchange ratio is taken at the value of . . the purpose of this study was to estimate the effective alveolar tension (pao eff) during spontaneous breathing with a new bedside technique which is simple non-invasive in normal subjects and patients with chronic bronchitis-emphysema. we also compared these values with the ideal alveolar po (pao (i)), measured from the alveolar air equation in which paco was substituted by the effective alveolar pco (paco eff) and with the alveolar po measured from the simplified alveolar air equation (pa ). this study is complemantary to previous work for the estimation of paco eff. methods: the subjects breathed quietly through the equipment assembly (mouthpiece monitoring ring, fleisch transducer head) connected to a pneumotachograph and a fast response and co analyzer. the method is a computerised calculation of the effective alveolar po quite similar to that of paco eff, obtained from the simultaneously recorded at the mouth expiratory flow, and co concentration versus time curves. results: the results showed a mean difference (pao eff-pa (i)) of - . kpa in normal subjects and - , in patients. the mean of the difference (pao eff-paq ) and (pad (i]-pao z) was much greater than . in all subjects. the limits of agreement for the difference (paozeff-pa (i))were - . to . kpa in normal subjects and - . to . in patients, while those for the differences (pao eff-pad ) and (pao (i)-pad ) were very large ( > - . to > . ) in all subjects. conclusions: the effective alveolar po is very close to the ideal one in normal subjects, tn patients pao eff may excessively deviate from pa (i) due to the observed significant difference between the alveolar/tidal volume ratio for o and that for co . the alveolar po measured from the simplified alveolar air equation (pao ) differed substantially from pao eff and pad (i) in all subjects. the essential role of glucoprotein hormone erythropoietin is to control red cell production. hypoxemia, reduced blood -carrying capacity and increased affinity of hemoglobin for are the primary stimuli for erythropoietin production. both anemia and hypoxemia induce rapidly erythropoietin secretion. kidney erythropoietin rna levels correlate inversely with hematocrit and directly with plasma erythropoietin level. similarly, hypoxemia increases kidney erythropoietin rna and plasma erythropoietin. the effect of hyperoxemia (pa >lo mmhg) on erythropoietin secretion isn't very well understood. the purpose of this study was first to evaluate the erythropoietin secretion in patients with acute respiratory failure and second to determine the effect of hyperoxemia on erythropoietin secretion in patients with and without anemia. sixteen patients with acute or acute on chronic respiratory failure needed mechanical ventilation were included in this study. these patient were divided in two groups. the patient who developed anemia were included in group i and the patients without anemia in group i . erythropoietin was estimated in venous blood in three stages. the first sample was taken during hypoxemia, the second during hyperoxemia and third during normoxemia. all the patients had high erythropoietin level during the hypoxemia period (mean value • mu/ml). during hyperoxemia etythropoietin levels were reduced in both groups ( mean value . + . mu/ml in group i, . • mu/ml in group ii). in normoxemia stage, erythropoietin increased again in anemic patients, and decreased more in the patients of group i . we conclude that hyperroxemia inhibit erythropoietin secretion in spite of anemia and tow arterial oxygen content. hyperoxemia may be a factor of the insisted anemia in with oxygen treated icu patients. the purpose of this study was to determine the relationship between clinical features of acute lung injury (all) and parameters like total proteins, total and individual phospholipids, the presence of paf, and acetylhydrolase activity in bal of mechanically ventillated patients. acetylhydrolase catalyses the cleavage of acetyl-group from the second position of the glycerylether backbone of paf, leading to its inactivation. mechanically ventillated patients were divided to three groups. group i includes patients without all; group ii, comprisespatients with moderate degree all, ( . <g-i < . ); and group iii comprises patients with severe ards (all score > . ). broncoalveolar lavage (bal) was obtained after infusion of normal saline at ~ to intubated patients and cooled immediately. cells were removed after mild centrifugation ( x g, min, oc). aliquots from the supernatant were used for total protein, phospholipid and paf analysis and determination. acetylhydrolase activity was assessed after incubation of bal with h-paf labelled on the acetyl group. released label was measured by liquid scintillation counter in the supernatant after trichloroacetic acid precipitation of the non-reacted substrate. kinetic characteristics of the enzymes were also studied. total phospholipids appear reduced in bal of patients with all, while total proteins increase. these factors appear to correlate with the severity of all. paf was not present in bal samples pretreatad with equal volume of % acetic acid to denaturate acetylhydrolase. detection limit for paf under our experimental conditions: pg paf/ml bal. instead, acetylhydrolase activity was detected in amounts increasing with the total protein content. background: intubated patients without lung injury or impaired breathing control normally display an inspiratory peak flow of below l/s. the aim of our study was to investigate the inspiratory peak flow generated by patients with acute respiratory insufficiency (ari). we had to take into account that both an inspiratory pressure support (ips) and the resistance of the endotracheal tube considerably influence the flow pattern generated by the patient. patients and methods: to investigate the non-influenced flow pattern we developed a new ventilatory mode which automatically compensates for the flow-dependent resistance of the endotracheal tube (automatic tube compensation, atc). furthermore, the mode maintains a constant tracheal pressure in inspiration and expiratio n . consequently, the measured flow pattern exactly corresponds to the flow pattern generated by the patient except that the ventilator modified for this mode (evita, driiger liibeck, germany) was not able to deliver a gas flow of more than l]s. we have investigated patients with ari arising from different reasons. results: the inspiratory peak flow measured in the atc-mode was . l/s _+ . l/s. the maximal deliverable flow of l/s was obtained in of patients. the figure shows the flow pattern under atc and ips in [~s] oi:) one of these patients. conclusions: patients with ari display a highly increased inspiratory peak flow. ventilators used for spontaneous breathing should therefore be able to deliver a gas flow of more than l/s. an overproduction of no and reactive oxygen species (ros) has been demonstratred in septic shock. ros and nitric oxide (.no) are free radicals which are known to react together leading to peroxynitrite anions that can decompose to form nitrogen dioxide (no ) and hydroxyl radical (oh~ thus, no has been reported to have a dual effect on lipid peroxidation (prooxydant via the peroxinitrite or antioxidant via the chelation of ros). in the present study we have investigated in different models the in vitro and in vivo action of no on lipid peroxidation. copper-induced ldl oxidation was used as an in vitro model of lipid peroxidation. ldl ( ~g apob/ml) was incubated with cu + ( , ~tm) in presence or absence of no donor (sodium nitroprussiate or glutathione-no) from to ~m. oxidation of ldl was monitored continuously with conjugated diene formation ( nm) and hydroxy nonenal accumulation (hne). exogenous no prevents in a dose dependent maner the progress of copperinduced oxidation. ischaemia-reperfusion injury (i/r), characterized by an overproduction of ros, is used as an in vivo model. anaesthetized rats were submitted to hour renal isehaemia following by hours of reperfusion. sham operated rats (sop) were used as control. lipid peroxidation was evaluated by measuring the hne accumulated in rat kidneys in presence or absence of l-arginine or d-arginine infusion. l-arginine, but not darginine, enhances hne accumulation in i/r but not in sop (< . nmol/g tissue in sop versus . nmol/g tissue in i/r), showing that in this experimental conditions, no produced from l-arginine, enhances the toxicity of ros. this study shows that the pro-or antioxydant effects of no are different in vivo and in vitro and could be driven by environemental conditions such as ph, relative concentration of no and ros, ferryl species...these conditions are impaired in circulatory shock. methods:" the diagnostic and therapeutic approach was standardized so that data collected over a -year period were comparable. a progressive deterioration of clinical conditions and/or pulmonary gas exchanges was considered as indication for my. variables potentially predicting the need for hv were derived from clinical and arterial gas data, extrapulmonary diseases, use of drugs, chest x-ray and ecg abnormalities. results: rv, performed with external and/or internal ventilators, was necessary in patients ( %). at the hospital admission, pac was higher and ph was lower in patients requiring rv ( pneumomediastinum, pneumothorax, ateleetasis and myocardial infarction are rarely seen in bronchial asthma. these complications occur as a result of the severe asthma.the aim of our retrospective study was to analyse the complications seen in acute asthma attacks. during the years through , patients were admitted to hospital in acute asthma episode. there were ( , %) pts with complications; mean age of yrs; females ( %). clinical history, ecg and chest radiogr~hs were analysed. the mean duration of bronchial asthma was yrs (range from months to yrs), all patients were atopics. there were four ex-smokem and one smoker. the worsening of asthma symptoms begun two days before the admission (range from to days). on ecg all patients had tschycardia. rightward shift of the qrs axis and st-t changes indicative of right ventrieutur strain were found in three pts. these were the transient fmdings that improved after curing the acute asthma attack. non-q myocardial infarction oeeured in one patlent and resulted from the hypoxaemia of asthma. hyperinfl~ion was the usual finding on the chest radiograpk pneumomediastinum and subcutaneous emphysema were apparent in five pts and required no additional treatment unilateral pneumothoraccs were present in two pts and needed eontimous intrapleural drainage; one of these patienst died in eardiorespiratory insufficiency. ateleetasis of right upper lobe was present in one patient. it oceured due to inspissated secretions and needed no additional treatment all these patients, except one who died, improved on lreaanent with oxygcr~ steroids, beta-two agonists, theophylline and antibiotics. in conclusion, complications occur in acute asthma episodes as a result of the severe asthma mediastir,*l emphysema and atelectasis are not serious complications. pneumothorax and myocardial infarction are very serious life-treatening complications and always have to i:m considered in taati~ts with sev~ asthma. acute bronchial asthmatic episodes represent one of the most common respiratory mnergendes, its maximmum expression "status asthmatiens" is one entity of low incidence, still it is a risk to the physical integrity of the patient. during a total of patients with diagnosis of status asthmabcas were hospitalized. out of these palients six had a near-fatsl asthma and they were subjected to a complex examination. near-fatal asthma was defined as either respiratory arrest or acute asttuua with paco greater than , kpa and/or an altered state of consciousness. mean age was , -d: , yrs, four male and two female sex. at presentation two patients suffered from coma, others were confused. they exh'bited severe dystmoes, diffieul~ speaking, used accessory muscles of respiration, increased whee~tg while two cases had silent chest on auscultation. cyanosis indicated a very severe asthma attack in all six patients. mean respiratory rate was ~ /min and puts rate .d: bts/imn. arterial blood gases revealed a pao of , ~ , kpa, paco of , • kpa and ph of , -+- , . area-careful evaluation they received conventional therapy (immediately continuous oxygen, impelled nebulization with high doses of betatwo agonists and ipmtropium bromide, intmvanous st~oids and theophylline). in two eases signs and symptoms of deteriorating airflow and respiratory muscle fatigue determined the need for mechanical ventilation. out of six near-fatal attacks aggressive lrealanent was suscessfull in four patients and fatal in two eases. one patient admittcxl in coma died in severe hypoxae~a upon one hour and one mechanicaly ventilated died from cardiac arrhythmia. life-threatening attacks in asthmatics in our group developed gradual worsening despite neatment which r symptoms in most other patients. one patient had "brittle asthma", other long-standing acute episodes ireated with systemic steroids. conclusions: idantitiechon of fatality prone subjects may lead to fttrther muetion of seveze episodes. respiratory affest and coma upon admission, severe dyspnoca with silent chest on ausouhation, oyanusis and use of accessory muscles of respiration constitute the basic cfinieal picture. hypoxasmia must be immediately eon'ected.the patients and physicians should be able to assess the severity of asthma, a major factor in near-fatal and fatal asthma attacks. objectives :our purpose was to asses if the evolution of patients with a adult respiratory distress syndrome (ards) ,shows any relation to the pulmonary or systemic origin of the disease and whether or not there were differences in the frequency of the syndrome in both groups. methods : randomized prospective study in multidisciplinary icu. one hundred and sixteen patients with a high risk developing ards were distributed into two groups. one was named systemic origin group(so) and the other pulmonary origth group (po).ai patients only showed one cause (pulmonary or systemic) with potential risk of ards.the patient's hemodynamic and respiratory status was evaluated every hours the first day and every hours the second and third day. at the end of hours the patients were diagnosed as ards or non-ards. measurements and main results : of the total patients, were finally included in the so group and in the po group.patients in so group and po group had comparable ages (p<. ).peep in both groups was comparable (=. ) at the mmnent of admission to the study. there were no statistically significant differences for cardiac index and systemic vascular resistances. the pulmonary vascular resistances (pvr) showed significant differences at h.(p<. ) and h. (p<. ).the oxygen comsumption (vo) in patients of the so group showed statistically significant differences at h. (p<. ) with respect to initial values.fifteen cases of ards ( . %) in the so group and twenty five cases ( . %) in the po group were identified. the time of onset of ards was _+ hours in the so group and + b hours in the po group.the final outcome was very similar th both groups : mortality of % in the so group versus % in the pc group. conclusions : the pathogenesis of ards depends on whether the lesion is originated at or outside the lung. the po group showed a sborter thne of onset of ards, a faster and more severe increase of pulmonary shunt and a higher percentage of patients developing ards compared with patients of the so group.the so group showed a higher and faster increase in puhnonary resitances tbat po group and a decrease th oxygen comsumption earlier and more severe than in the po group. these data thus seem to show that there could be two mechanisms involved in the genesis of ards depending on the cause. the fact that the ards genesis is shorter in the cases of pulmonary etiology with faster impairment of pulmonary shunt, and a slower increase in pulmonary resistances in this pulmonary group, would indicate that the underlying mechanisms responsible for the hypoxemia are different to those which thitiate the increase in pulmonary resistances. finally, the exclusive inapairinent of oxygen consumption, which appears earlier than the onset of ards in the systemic origth group, could show the generalized character of the process in this group. perfusion of prostacyclin (pgi ) to treat pulmonary hypertension in adult respiratory distress syndrome (ards) worse pulmonary gas exchange due to a marked impairement of ventilation/perfusion mismatch. recently has been shown that if prostacyclin is given by aerosol instead of intravenous the net effect is an improvement of arterial oxigenation due to a redistribution of blood flow to well ventilated areas. objectives: to asses the effects of inhaled proatacyclin on pulmonary haemodynamics and gas exchange in patients with severe ards. methods : two patients with severe ards (murray score > ) recived inhaled pgi at - ng.kg.min " using an ultrasonic nebulizer. haemodynamic measurements, arterial and mixed venous blood gas analysis were performed before and after rain of pgi inhalation. results: short-terro p~i inhalation improved pulmonary g-~ e-'~hange in both patients. arterial oxygen partial pressure (pao ) increased from to mmhg in patient and from to in patient , the ratio pao to the fraction of inspired oxygen increased from to (patient ) and from to (patient ). venous admixture decreased from % to % and from % to % in patient and respectively. mean pulmonary artery pressure decreased slightly from to mmhg in patient and from to mmhg in patient . no effects on systemic haemodynamics were observed in any patient. conclusions: pgi inhalation improves gas exchange and produces selective pulmonary vaaodilation, thus can be an alternative therapy for the treatment of pulmonary hypertension and hypexemia in patients with severe respiratory falllure. methods: we treated ards-patients (age yr ( - ) mean, range) during - . the lowest pao /fio -ratio was ( - ), the worst murray score . ( . - . ), icu-stay ( - ) days and hospital mortality %. the costs of intensive care were calculated according to intensivity of patient care as assessed by tiss-scoring (therapeutic intervention scoring system). the more intensive the care, the higher are the costs. costs per year of life saved (=life-year" in us $) were compaired by other medical treatments ( - ). it is assumed that the mean expected length of remaining life in ards-survivors after intensive care is years. treatment life-year ($) ' bone marrow transplantation (acute leukemia) lowering cholesterol using iovastatin treating hypertension using nifedipine heart transplantation intensive care of ards-patients conclusions: intensive care of patients with severe ards is highly more cost-effective as compared with many other routinely used medical treatment strategies, the usually good recovery and the reasonable quality of life in survivors justifies investments to care of these patients ( ). there is a close correlation between these two methods of measuring evlw. however there is an underestimation of . % in this kind of pulmonary edema ( oleie acid induced ) with the double dilution method. although the size of the sample is small, in normal lungs there appear not to be this underestimation. the effect of peep on evlw has been studied with contradictory results, probably as a consequence oft differences in methods of measuring evlw, variations in the type and severity of lung injury, and different timings of peep application. objective= ) to analyse the effect of different levels of peep ( , and omh ) on evlw during hpe; ) to establish whether increases in intrathoracic pressure due to high peep levels can obstruct lymphatic drainage. material and methodet hpe was provoked in groups of dogs by inflating a foley catheter in left auricular to a pressure of - r~uhg. peep levels of , i or m~hg were applied. resultst objective: to assess the effect on extravascular lung water (evlw) of the application of peep and the reduction of vt in an oleic acid pulmonary edema model in pigs, using three ventila~ary strategies. material and methods: twelve adolescent pigs (weighing over kg) were randomly divided in three gmups immediately alter infusing via a central vein . ml/kg of oleic acid to produce a permeability pulmonary edema. the ventilatory parameters for each group were as follows: group i (n= ) : vt: - ml/kg; zeep. group :(n= ) : vt: - ml/kg; peep: cm h . group :(n= ) : vt: - ml/kg; peep: emil . (resulting in permissive hypereapnla) after a four-hour period of ventilation the animals were killed and the lungs excised to calculate gravimetrically the extravascular lung water using a standardized procedure ( hemoglobin content method ). ill evlw (ml/kg) group obiective: in the postoperative period, maintenance of adeguate arterial oxygen tension is a major problem in morbidly obese patients probably because of a large reduction in functional residual capacity (frc). the aim of this study was to evaluate the effects of peep on respiratory mechamcs and gas exchange in this kind of patients. methods: in nine postoperative mechanically ventilated morbidly obese patients (bmi> kg/m ) we partitioned the total respiratory system mechanics into its lung ( ) and chest wall (w) components using the airway occlusion technique associated with the esophageal balloon, during constant flow inflation (jap ; : ) . at three different levels of peep ( , , cmh ) we measured: compliance (cst), airway (rim) and "additional" (dr) resistance, frc and gas exchange. obiectives. to describe the use of prone position in our icu we analyzed the clinical records of all patients admitted in - , selecting adult patients with arf defined as: intubation and pao /fio < mmhg plus an fio > . or peep> cm i . results. patients met the arf criteria: of them ( . %) underwent prone positioning (p+). prone position use began in the early phase of arf ( . • days from the beginning, range - , median ). out of p+ pts were treated with controlled ventilation (cppv or pcv), while were on assisted ventilation (simv+ps) and on spontaneous breathing (cpap). only pts were awake when turned prone, while pts required adjuncts of sedation to tolerate the change of position. the duration of prone positioning was variable (average lenght . • h, range . - h). only minor side effects were observed (eyelids and facial edema, chest and facial pressure bruises). we consider responders (r+) those patients presenting at least . mmhg increase in pao /fio : / patients ( . %.) were responders when first pruned. the pao /fio changes induced by prone position are reported in the figure. pao /fio increased when patients were pruned (*p< . ) and remained higher than baseline values when returning supine(*p< . ). paco remained unchanged. prone positioning was used at least twice in / ( conclusions. this retrospective analysis confirms that prone positioning improves oxtgenation in the majorib' of arf patients. altough we have no available criteria to discriminate in advance r+ from r-pts, we now routinely consider the use of prone position in the treatment of severe arf. palo a, otivei m*, galbusera c, veronesi r, sala gallini g, zanierato m, iotti g, braschi a.servizio anest. e rianim. i, *laboratorio biotecnologie e tecnologie biomediche irccs s. matteo, pavia, italy inhaled no can improve arterial oxygenation and reduce pulmonary hypertension in ards patients; little information is, however, available about the dose-response curves. methods seven ards patients (lis . +. ) submitted to mechanical ventilation randomly received inhaled no doses in increasing or decreasing sequence: . , , , , , and ppm. reference measurements were obtained before and after the entire period of no inhalation. hemodynamic parameters and blood gases were measured after min in each condition. cmv was administered under sedation and paralysis, with constant ventilation, peep (lol-_ cmh ) and fit (. +. ). the changes in vt and fit due to the no ( ppm in n ) injection in the ventilator external circuit were compensated for. results . the dose of . ppm, ineffective on papm, significantly improved oxygenation. the increase of pat and the decrease of q'va/q' and papm were nearly maximal at - ppm. no deterioration of arterial oxygenation was observed at no doses as high as ppm. co exchange was not influenced by no inhalation. systemic hemodynamic variables did not change throughout the study. these results suggest that a concentration around ppm is adequate for obtaining maximum effects on hypoxemia and pulmonary hypertension in patients with ards. low-dose inhaled nitric oxide (no) induces redistribution of pulmonary perfusion in patients with severe ards and causes improvement of oxygenation [ ] . however, addition of exogenous lowdose no in the inspiratory gas mixture might be only a replacement of missing atmospheric no ( - ppb) in hospital central-supplied medical air. [ ] we have realised nitric oxide measurements in ten healthy volunteers, ( smokers and non-smokers) breathing with a mouthpiece and occluded nostrils through a ventilator circuit, with separation of inhaled and exhaled gases by a valve. no concentration was measured with a double-chamber chemiluminometer (environnement sa, france) and with charcoal/silicate purified compressed air. there was no nitric oxide detectable in the inspirat ry limb of the ventilator. unfiltered central supply medical air contained : - ppb of no and - ppb of no , whereas central supplied oxygen was no/no free. samples were taken after equilibration periods of minutes, with increasing fit levels of . , . and . for subsequent minutes periods; paired values were recorded every s. the mean no value was . ppb (sd . ) and n o significant differences were found for different fit levels both in smokers and non-smokers. these data suggest that the no concentration of pulmonary origin in the exhaled air of' healthy volunteers is probably lower than that reported by other authors [ ] and that, previously reported, differences between smokers and non-smokers are not always striking [ ] . we suggest the use of activated charcoal/silicate filters for clinical trials in order to achieve standard conditions. [ objective: to compare efficacy and safety of two doses of salbutamol. methods: sixteen adults who had severe acute a~hma were randomly assigned to receive either rag (n= ) or rag (n= ) of nebulized sulbutamol. both groups were similar with respect to age, duration of a~hma, duration of attack before arrival at the hospital and severity of a~hma according to baseline measurements (table) . evaluation was performed , , and rain after the start of nebulization. results: compared with mg regimen, mg regimen resulted in the same improvement in peak-flow and fischl index (figure). the changes in heart rate, respiratory rate and pace did not differ significantly between both groups. the incidence of side effects, which included tremor, palpitations, cardiac arrythmlas and other symptoms, was not sj~ificanfly different in the two populations. conclusion:the results of this study suggest that nebulization of ng of salbutamol is not more effective than rag in the initial treatment of acute severe asthma in adult patients. the prognostic factors of neutropenic patients admitted to the icu remain poorly known. the aim of this study was to determine the respective weight of underlying malignancy and organ system failures on the outcome of these patients. patients and methods: the charts of neutropenic patients (wbc < /mm and/or pmn < /ram ), admitted to the icu between and , were retrospectively reviewed. the characteristics of the neoplastic disease (h~emopathy or solid tumor, tumoral evolution, duration of cancer disease and of neutropenia), the mac cabe's score, the organ system (respiratory, hemodynamic, renal, neurologic, hepatic) failures and the severity scores (saps, saps ii ,osf) were registred within the st day in the icu. when discharged from the icu, the patients were classified as alive or dead. results: fifty-seven patients ( . %) had a h~ematologic malignancy, and ( . %) a solid tumor. fifty-nine of the patients died ( . %); the mortality rate did not differ between both groups ( . and % respectively, p = . ). with univariate analysis, none of the tumoral features is linked to the prognosis; only the respiratory (p < - ) and cardiovascular (p < - ) failures, and the number of organ system failures (p < - ) are associated to the risk of death. the saps (p < - ) and saps ii scores (p < - ) were higher in patients who died. with multivariate analysis (logistic regression), only the respiratory failure is correlated to the risk of death (p = - ); neither the features of the underlying malignancy (p > . ), nor the duration of neutropenia before admission in icu (p = . ), nor the severity scores figs ii: p = . ) are linked to the outcome. conclusions: the tumoral characteristics do not modify the prognosis after admission to the icu. they should not influence the decision to admit or refuse a cancer patient in the icu. respiratory failure at icu admission has the predominent weight on the risk of death in the icu. patients with respiratory acidosis due to asthma occasionally require levels of mechanical ventilation that place them at risk for barotrauma. a few case reports have described the use of an extra-corporeal membrane oxygenator(ecmo) circuit as an alternative means of co removal. generally, this has been used for short periods of time (< h) without serious complications and with low blood flows through the extra-corporeal circuit. we report a case of refractory asthma who could not tolerate even small-volume breaths from a mechanical ventilator due to severe bilateral airleak. ecmo therapy was initiated at the referring hospital prior to helicoptor transport. high blood flows were used ( % of the patient's cardiac output), sufficient to achieve both co removal and oxygenation. satisfactory gas-exchanged was accomplished (pco = - mmhg) with nearly total lung rest for a prolonged period ( h). however, the long ecmo duration was associated with two severe complica-ti ns: ) bilateral hemothoraces due to anticoagu!ation in the extra-corporeal circuit, and ) prolonged weakness as a result of neuromuscular blockade for six days. the patient was discharged from the hospital in good condition. we present the respiratory and hemodynamic features of this case aw well as the potential complications of ecmo therapy in asthma. objectives: parameters derived from tidal expiratory flow ~e) and volume (vt) can be used to detect airflow obstruction in copd patients who might be unable to perform forced spirometry (e.g., icu). however, indices such as ave/v t and at/re are highly variable (thorax, : ; ) . methods: we investigated whether the standardized for v m effective time (teff~) of a tidal breath, which is derived by asimple mathematical procedure (teff,= j'vdt/vt ), is a more reproducible and sensitive detector of airways obstruction, we studied nine normal subjects ( male, -+ yr) and copd patients ( male, -+ yr) in the seated position, with a noseclip on. they breathed quietly, through a pneumotashograph to measure flow (v). volume was obtained by numerical integration of thellow signal. each subject had an initial - min trial run, in order to become accustomed to the apparatus and procedure. when regular breathing had been achieved, all breaths over a min time interval were recorded. the mean value of six consecutive breaths (ers criteria) for each subject was used for analysis under the condition that within session variation of tidal volume (vt) was < %. lung function tests were: in normals (mean-sd), fevl%pred = • fevl/fvc%= -+ % , and in copd patients, fev~%pred= __. and fevi/fvc%= --. %. results: values are shown as mean-..+-sd in the following a su~ve~ os literature sources p~oves that t~aditlona], i.e. medicinal medication and physiothe~apeutic methods os t~eatment often p~ove to be insufficientl~ effective both currently and in the ~emote future. the goal of this study was to investigate the efficacy os t~eatment of b~onchial asti~ma patients by means os speleo-and artificial sp~ay therapy. speleotherapy t~eatment was conducted in the conditions os mic~oclimate os salt mine in solotvino hospital. a~tis sp~ay the-~apy was conducted by means os a self-made device. ou~ method is based on the p~inci-~ le os using the majo~ facto~ of speleo-he~apy -highly dispe~sed sp~ay s sodium chloride. the obtained ~esults ~e~e analyzed in five g~adations. at the end os the speleothe~apy improvement and considerable improvement was observed in , ~ os patients; inconsiderable improvement -in , ~ os patients. having evaluated the e~s os t~eatment using a~tis sp~ay therapy the indices a~e , h and , ~ ~espectively. remote ~esults of t~eatment a~e an important index os t~eatment, the ~esult os ~hich ~e~e studied by means s a ~uestionnaive-method. patients ~ho had been t~eated by speleothe~apy mo~e f~eguently ~e-po~ted a ~elapse in disease ust afte~ the course o~ t~eatment ( , h). ho~eve~, in a ]ate~ phase the ~emission ~ould last ]on-~e~ (s months in , ~ os patients, till one yea~ in ~ ~). in , ~ os patients who passed the co~se os a~tificial sp~ay therapy a ~elapse was ~egiste~ed immediately as the co~se os t~eatment. then thei~ condition stabilized ~hile in , ~ os patients a period os ~emission lasted s ha]s a yea~. , ~ of patients dida't ~epo~t a ~elapse of the disease du~in~ one yea~. evangelismos hospital, critical care department, athens, greece method#: mechanically ventilated patients ( copd, ards, other pulmonary diseases) were studied in two phases: ) during the acute phase of respiratory failure; ) during recovery - days later. we measured mip and monitored the pattern of breathing while the patients were breathing spontaneously through the respirator (pressure support mode with - cmh ) until either the point they were unable to sustain spontaneous breathing (sb) any longer (phase ) or for two hours when they could sustain sb indefinitely (phase ). subsequently the patients were sedated, paralyzed and mechanically ventilated. then we simulated the pattern of sb at the end of the sb trial by manipulating the variables of the ventilator and assessed respiratory mechanics b y the end-inspiratory and end-expiratory occlusion technique. . during recovery, a combination of reduced inspiratory load and increased venfilatory capability makes a patient previously unable to sustain sb to breathe spontaneously. . inspiratory load is reduced during recovery, mainly because both intrinsic peep and breathing frequency are diminished. obiectives: although elevated concentrations of a few cytokines have been shown to be present in the bronchoalveolar lavage (bal) fluid (balf) of patients with the adult (acute) respiratory distress syndrome (ards), the pethogenesis of ards is largely unknown. leukemia inhibitory factor (lif), a growth factor recently recognised as a polyfunctional cytokine integrated in cytokine networks was measured in unconcentrated balf of patients from different patient groups. methods: lif was measured in balf by means of a specific and sensitive elisa (detection limit pg/ml)in balf (lavage of x ml in the right middle lobe). results: lif was not detected in the balf of healthy control patients and in only one ( pg/ml) out of patients at risk for ards (after cadiopulmonary bypass surgery) who underwent bal h after the end of the extracorporeal circulation. high and detectable levels were found in the unconcentrated balf of out of patients with full-blown ards ( + , mean + sem, range - pg/ml). there was a good correlation between the level of lif in the balf and a number of markers of inflammation: neutrophils/ml (r: . , p= . ), albumin ( r: . , p= . ) and protein level (r: . , p= . ). conclusions:the biological role of lif in these balfs is not readily explained by its currently known actions and it is unkwon whether lif contributes to or is a response to local tissue damage. our results indicate that this cytokine with lots of interesting _functions is a pert of the inflammatory cytokine cascade in ards. background and obiective : we recently demonstrated that cisapride -a new prokinetic drug -enhanced enteral feeding in a heter genoas group of ventilated icu patients by significantly accelerating their gastric clearance (crit care meal, ; : - ) . it remains unknown, however, whether certain subgroups of patients might benefit more from adding cisapfide to their enteral nutrition regimen than others. patients with chronic obstructive pulmonary disease (copd) might represent such a subgroup since their illness and its specific treatment put them at risk for gastric emptying disorders. design and setting : prospective, consecutive sample study in an adult medical intensive care unit in a university hospital. patients : mechanically ventilated and hemodynamically stable copd patients. interventions : gastric emptying was evaluated by bedside scintigraphy and expressed as the time at which % of a tcg~-labelled test meal was eliminated from the stomach (t / ). baseline data (do) were recorded after enteral nutrition reached to ml daily. scintigraphic measurements were repeated days after cisapride ( ml orally, q.i.d) had been added to this regimen (d ). patients were considered cisapride responders when gastric clearance improved by more than % from baseline. results : normal values for the test meal and for scintigraphic acquisitions obtained in the supine position were found to be + min. in healthy volunteers (crit care med, ; : - ) . five patients responded to cisapride (t / : + rain vs. + min at do and d , respectively) and five did not (t / : + min vs. _+ rain at do and d , respectively). in contrast with non-responders, all five responders had clinically significant maldigestion at baseline (excessive (> ml) gastric residues, vomiting (> times/day and abdominal distension) which disappeared in of them after the administration of cisapride. conclusion : copd patients who tolerate enteral nutrition well have basal gastric emptying times which are comparable with those of healthy volunteers and are not influenced by cisapride. however, cisapride treatment provides both scintigraphic and clinical improvement in those copd patients who exhibit clinically obvious gastric emptying disorders. cernv v., dostal p., zivny p., zabka l. dept. of anesth. and critical care, charles university, faculty hospital, i-irade~ kralove , czech republic objective: the aim of the study was to evaluate the effect of early entera nutrition started within hours of injury on the incidence of multiple orgar failure (mof) in trauma patients requiring vantilatory support. methods: after institutional approval patients were enrolled in the study enteral feeding was begun within hours of injury in trauma patients (en group) admitted to icu. nasuenteric tube was placed as soon as possible after admission into the distal duodenum under endoscopy. additional parenteral nutrition was used to meet patients energy and protein requirements. the control group (pn) consisted of patients fed during this period paretuerally. severity score apache ii, trauma score, cumulative balance of nitrogen (g), incidence of mof (three and more organs) and length of ventilatury support (days) were calculated. values are expressed as mean + sd. results: tab introduction : parenteral nutrition (pn) is an important aspect in the optimal treatment of patients on gastroenterology or intensive care. the aim of this bi-center study in patients has been to assess tolerence and efficacy of a new protein-lipid mixture for pn from a simple preparation. patients and m~hods : patients were selected in two hospitals (tenon and saint-lazare, paris) and were divided into two groups : group a (gastroenterology~ l short bowel syndrome) and group b (intensive care, surgical patients). all patients likely to require pig for a period of days (group a) or days (group b) were studied. the pn regimens administered were the following : combination with g of mct/lct fat emulsion end , g of nitrogen, in liter end glucose requirements were met by imfizsion of l liter of glucose - % via a "y " connection. lipid thus provided % of the non introgen calories. total daily calorie intake was to ] kced. this study monitored, before and at the end of infusions, the sennn albumin (alb), preaiburtun (prealb), triglycendes (tg), cholesterol (cs), and the serum ammotransferases (sgot and sgpt) end alkaline phosphatase (alp) activities. statistical significances were calculated using the wilcoxon-tost. introduction: many cu patients present a catabolic illness in response to inflammation and infection, characterized by a rapid loss in skeletal-muscle mass despite optimal nutritional support. growth hormone (gh) is responsible for a rise of lipolysis, enhancing the energetic balance, and of protein synthesis. recombinant human gh (rhgh) is nowaday available for clinical use, but its cost is very high. therefore, rhgh should only be prescribed to icu patients when its efficacy can reasonably be anticipated (ie. when the patients are catabolic or stressed, but in order to avoid overprescription for unstressed patients and for those who are overly catabolic). hence, we, as others, recently demonstrated that rhgh had no favorable effect in highly stressed icu patients. objective: to detect on a clinical basis, low (ls), mild (ms) and severe stress (ss) states in icu patients and validate this clinical judgement by objective metabolic mesurements, in order to select early those icu patients potentially able to benefit from rhgh therapy. methods: consecutive icu patients were prospectively stratified as ls, ms and ss by two experienced icu senior consultants (temperature; agitation; heart rate; arterial blood pressure; presence of an infection; respiratory rate; exogenous catecholamines). anabolic (insulin, igf- , gh) and catabolic (cortisol, ghicagon) hormones, and nitrogen balance were determined for each patient within hours after admission in the icu. metabolic and clinical data were then compared. the clinical stress states determined by icu physicians correlate with an objective metabolic assessment. therefore, the patients who will more likely benefit from adjuvant rhgh therapy can be detected simply and early. a prospective study on rhgh therapy in ms icu patients is in progress. berger mm md , chiolero r md , pannatier a phd , berger l , cayeux c , voirol p , hurni m md . surgical icu, pharmacy, and cardiac surgery, chu vaudois, ch-iotl lausanne, switzerland objective. nutrition of the compromised cardiac surgical patient is challenging. numerous factors influence the gastrointestinal (gi) absorption function, among which gut perfusion, which depends largely on the systemic hemodynamic status. patients in hemodynamic failure are prone to organ failure, and may benefit from an early jejunal feeding. the study was designed to assess the absorption function after cardiac surgery in patients with adequate and altered hemodynamic status, using paracetamol as tracer of gi absorption. methods. after cardiac surgery, patients, aged _+ years (mean_+sd) were assigned to groups (anaesthesia: fentanyl gg/kg + midazolam): group (n= ): reference group, with normal hemodynamic status, easy recovery. group ('n= ): patients in low output syndrome, cardiac index < . i/m on day (d ) after surgery, requiring prolonged intensive care, mechanical ventilation + nutritional support. paracetamol g, was given intragastrically on d + d : plasma levels measured (h.p.l.c), at administration (to), t - - - - - and rain. hemodynamic status assessed with pulmonary artery catheter. healthy subjects served as controls. results. compared to healthy controls, absorption was strongly reduced on d in all patients (no difference between groups). on d , peak paracetamol level was significantly lower in group (low cardiac output): in group the area under the curve on d and d were similar. there was a large inter-patient variability, reflecting the hemodynamic status. conclusion. gi absorption was decreased on d in all patients, and reverted to normal between d and d in case of normal cardiac function, but not in case of low output syndrome. the decrease on d can be attributed to fentanyl, known to slow down the gi transit. in patients with cardiac failure, correction of altered absorption was correlated with the hemodynamic status, suggesting that gi absorption is dependent on adequate splanchnic perfusion. the aim of the work was to define specific significance and evaluate efficiency of enteral component of infusion therapy in the intensive care of gastroenterotogic patients of surgical profile with pyo-septic complecations. there were used the methods of radial diagnostics and polyelectrography; the laboratory control on oxygen-transporting function, volumetric and hemodynamic state, changes in metabolic, hormonal and immunologic status was conducted. from january, [ till november, there was carried out the randomized study of patients with general purulent peritonitis; among them persons constituted the control group and -the main one. in the main g~oup the intestinal lavage, enterosorption, enteral introduction of nutrient solutions with gradual turn to enteral nutrition by equalized mixture "ovolaet" were started from the first hours after operation. the data obtained allowed to define the specifity of the program of artificial medical nutrition in the group of examined patients, based on necessity of individual selection of media for enteral introduction depending on the stages of intestinal insufficiency syndrome. it was shown that inclusion of enteral component into the program of infusion therapy during early periods stabilized circulation in the regime of moderate hyperdynamia, considerably decreases the deficiency of circulating blood volume, normalizes the values of oxygen transport, consumption an}d extraction, provides the optimal level of mycardial adaptive possibilities without tension of its compensatory functions and pulmonary circulation overload. due to combined application of parenteral and enteral nutrition the metabolic processes are shifted towards anabolism. this is supported by decrease to normal values in the contents of blood aggresive hormones (acth,hydrocortisone) and increase in somatotrophic hormone. the complete parenteral-andenteral nutrition influences positively on restoration of cellular and tumoral immunity, activates the factors of organism nonspecific protection and recovery from immunodepression, prevents the development of immunodeficiency. impact tm vs control. s atkinson, n maynard, r grover, e sieffert, r mason, m smithies, d bihari departments of surgery and intensive care, guy's hospital, london, u.k objectives: comparison of the effect of an immunonutrient enteral feed versus a control on the outcome of a mixed intensive care unit (icu) population. methods: admissions to this multidisciplinary adu)t icu thought likely to stay more than three days and with tube access to the gi tract ~r randomised to receive either impact tm, a feed with supplemental arginine, dietary nucleotides and omega- fatty acids, or an isocaloric and isonitrogenous control feed. study end points included mortality and icu stay. approval was obtained from the hospital ethics committee. rosults: patients were entered into the trial. the two groups were well matched for age, sex, and admission apache ii with an overall mean admission risk of death of . (std. dev. -+ . ). on an intention to treat basis, there was a no significant difference in icu mortality, icu stay or standardised mortality ratio (s.m.r.) between the two groups (see table) . similarly, there were no differences after stratification for patients receiving or more litres of feed. conclusion: there is no evidence of an effect of impact@, an enteral immunonutrient feed, on pre-determined end-points (icu mortality, icu stay or standardised mortality ratio) in a mixed intensive care unit population over that of an isocaloric, isonitrogenous control feed. objeeflves: evaluate changes of blood laatate levels according to patient medical status after cvvhd initj,~ion using dialysate solution containing lactate. method: review of medioal records of consecutive patients ~eated by cvvhd (dialysate solution hmnosol lg , hospal,uk, lactate concentration retool/l). date obtained hr before and - hrs at~er cvvhd initiation were analysed. results: all data are presented as mean + sem. in one patient, pre end post filter lactate levds were measured during standard cvvhd setting (blood flow ml/mlu, dialysate solution flow i /hr), and approximate daily lactate flux into the patient was calculated to be as high as mmol/d. lactate leveh measured after cvvhd initiation increased significenfly compared to baseline levels ( . + . axtd . + . ,respectively; p< . ,paired t-test). when patiente with increased basal lactete (~- ) were compared to paliente with normal basal values (n= ), no difference in laotete increase was fmmd (p= . , manova). patiente with severe liver dysfunction ( points in mop scomlg, n= ) had higher basal laotate levels than patiente with normal or slightly abnormal liver teste ( or point in mof scoring, n=ll), rite values being . + . and . + . , respectively (p< . , student t-test). increase in blood lactate did not differ between these two groups after cvvhd was stetted (p= . , manova). in pafiente with invasive hemedynamio mo~, no oorrelation batween changes in lactate levels and eitlm" changes in oxygen ddivery (t =o.ol; p--o. ) or oxygen consumption (reversed fie, k) (r -q).o ;p-- . ) were found after cvvhd initiation. conclusion: blood lactate increases on cvvhd with dialysate soh~on rich in lactate. this increase is predominantly caused by influx of lactate into the blood via the filter end does not seem to depend on the liver fimotion and/or oxygen metabolism changes. objectives: the study was designed in order to determine the effect on plasmatic proteins, of two types of aminoacids solutions of parenteral nutrition (pn) adapted to stress, having different concentration of branched chain aminoacids (bcaa), when applying to politraumatized critical patients. methods: a prospective study was performed using a randomized double blind design of polytraumafized patients, split in two groups of ten patients each, with mean ages of _+ an -+ years. due to their condition, all patients required p.n. for at least days. both groups were subjected to isocalorie and isonitrogenous solutions ( ci/kg/ day and . g of nitrogen/ks/day), varying only in the concentration of bcaa; solution a having a % concentration and solution b %. blood samples determinations during days , , , after the beginning of treatment with p.n. were total proteins., albumin, trandferrine, protein binding retinol; prealbumine and fibronectine. the anova test (one and two way) was used to compare the values between the two groups. results: the administration of solution a, showed statistically significant increases in the determinations of the values of protein binding retino] (p < . ) and prealbumin (p < . ). no significant increases were observed in the values of total protein, albumin, transferrine and fibronectin. solution b produced statistically significant increases only in the values of total proteins (p < . ). the remaining proteins did not changed from their control values during the whole period of pn administration. comparing both groups, no statistically significant differences were observed related to the type of diet. nevertheless, differences were found in total proteins, albumin, protein binding retinoi, fibronectin (p< . ) and prealbumin (p < . ) in relation to the time course of pn therapy. only the albumin values showed significant differences (p < . ) when considering the interaction of both the type of diet and the time course of pn. conclusions: . solutions of pn adapted to stress, can maintain the control values of slow turnover proteins and improve the values of rapid turnover proteins. . no significant differences on plasma proteins were found between the two solutions having % or % concentration of branched chain aminoaeids. &determination of rapid turnover proteins does not seems useful for discriminating different solutions of bcaa during pn. obiectives; the hormonal changes in the post-traumatic situation often leads to an elevated blood glucose and a negative nitrogen balance. to reduce the elevated glucose production by aminoacids the apprication of xylitol may be an alternative energy source. in a double-blind randomized study we investigated the effects of a xylitol/glucose solution (group a: aminoacids g/i; glucose/xylito g/ g/l) on metabolism and particularly on pancreatic and liver enzymes compared to a glucose based nutrition solution regimen (group b: aminoacids g/i; glucose g/i). methods: the clinical trial was carried out after the approval by the local ethical committee on patients with severe brain injury. there was no difference in body mass index bmi (group a: . +/- . kg/m and group b: . +/- . kg/m=), age, and sex. daily individual energy expenditure was measured by indirect calorimetry (deltetrac "~). nutrition was started - hours after trauma or surgery with carbohydrates and aminoacids. fat was added h after nutrition had started. to analyze the effects on pancreatic and liver enzymes we investigated the following parameters for days: blood gtucose, serum lipase, serum amylase, asat, alat, ~gt, ap, and serum cholinesterase (che). results: due to the daily indirect calorimetric measurements energy requirements were satisfied. there was no difference in blood glucose concentration and cumulative nitrogen balance between the two groups. neither were there any significant changes in asat, alat, ap, and che for days in both groups. serum tipase steadily rose to lull in group a and . lull in group b, respectively. conclusions: there was no measurable influence of either nutrition solution on liver enzymes. the xylitol/glucose nutrition regimen does not have any advantage over the glucose based nutrition solution concerning blood glucose level or nitrogen balance. the elevation of serum lipase to a -fold level in either group needs further investigation on trauma patients. the effects of fat emulsions in lung function, particularly in lungdamaged patients, have been attributed to alterations in pulmonary vascular tone caused by eicosanoid production modificatione. as the eicosanoid production may depend on the fatty acid profiles of the intravenous fat emulsion, haemodynamic, pulmonary gas exchange and plasma levels of prostanoids were investigated in acute respiratory distress syndrome (ards) patients, during different intravenous lipid emulsions (providing different prostanoid precursors). we studied in a randomized double-blind design groups (n= each) with ards. group i (lct) received a fat emulsion with long chain triglycerids (lct- %), group ii (mct) an emulsion containing a mixture of medium and long chain triglycerids (mct/lct / - %) and group iii placebo (control), during h ( mg/kg/min each). we measured before, at the end of h infusion, and h after the end of the infusion: lipaemia, arterial and venous blood gases, pulmonary and systemic haemodynamics, and plasmatic levels (arterial and in mixed venous sample) of eicosanoids (txb=, -keto pgf~,, and ltb ). at the end of the fat emulsion, groups (i and il) to , • to , • mmol/i), the paoz/fio z remained unchanged in the three groups; no changes in intrapulmonary shunt (qs/qt) were shown; neither in the mean pulmonary artery pressure. in contrast, only in the lct group: cardiac output and oxygen consumption increased significantly ( . % and %) (p< . ). eicosanoids were increased at baseline compared to reference values (p< , ). a decrease (p<o, l in the arterio-venous difference of the vasodilatador prostanoid ( -keto pgf~=) was shown in lct group. our results indicate that fat emulsions in ards patient do not influence pulmonary gas exchange, provided that the perfusion rate were keept at mg/kg/min. the present study was designed to evaluate the metabolic changes of a carbohydrate-based diet versus a fat-based diet on oxidation rate of substrates and energy muscle metabolism in patients with an acute exacerbation of chronic obstructive lung disease. patients were mechanically ventilated with a volume-cycled respirator. after an overnight fast, patients were randomnly treated with a continuous enteral feeding over a nasogastrie tube with a carbohydrate/fat ratio of / in group i (n= ) , and a carbohydrate/fat ratio of / in group i] (n = ) during consecutive days. indirect calorimetry was set at baseline and hours later the enteral feeding was started. muscular quadriceps biopsy was performed on baseline and on day of enteral feeding. urine was collected during hours and was used to measure h urea nitrogen production. the caloric intake was set according to the measured resting energy expenditure. respiratory gas exchange rate were measured using a computerized open-circuit indirect calorimeter. quadficeps femoral muscle samples were obtained by muscular biopsy after local anesthesia. analyses of glycogen, glucose -phosphate, lactate, phosphocreatine and adenosine triphosphate (atp) and enzymes (glycogen synthase and glycogen phosphorylase) were determined. after h of nutrition patients in group i showed an increase in carbohydrate oxidation (from . % to . %, p= . ), and in group ii a decrease in protein oxidation (from % to %, p= . ). after days of enteral feeding a tendency to increase in glycogen concentration (group i, p= . ; and group ii,p= . ) was observed. while patients in group i showed a tendency (p= . ) to decrease glycogen phosphorylase, patients in group ii maintained these enzymatic levels. the increased in glycogen was correlated in group li with degradation enzyme (p = . ). in group i, the pao /fio ratio increased after days of treatment (from . to . ; p= . ), but no changes in days of mechanically ventilation, length of stay in icu, or mortality rate was evidenced between groups. it is concluded that the oxidation rate of substrates used for energy production varies according to the caloric sources administered. with nutritional therapy muscle glycogen concentration increases in both diets, with different enzymatic influence. more studies are warranted to further assess the clinical implications of the different pathophysiologic behavior of the two diets. under certain experimental and human conditions (radiation and/or thermal injury) the gi mucosa is unable to perform this protective function and could play an important role in the pathophysiology of the syndrome of multiple organ failure (smof). the objective of the present multicenter study was to know the gi mucosal permeability in critically ill patients and the relationship with their outcome. the method used to assess the integrity of the gi mucosal barrier measured mucosal permeability to various hydrophilic compounds. specifically, we measured the urinary excretion ratio (uer) of two sugars (lactulose and mannitol) that had been previously administered through a nasogastric tube. urinary excretion rate was measured in healthy humans (control) and in patients admitted to the intensive care unit (icu) at days , and . the apache ii of the patients studied was _+ . there was an increase of uer in the critically ill patients compared with controls (o. _+ . vs . _+ . ) (p< . ). in contrast, no changes in uer between days , and were observed ( . -+ . . significant changes were also established in the different groups: major and minor surgery, general and epidural anaesthesia , transfused and non transfused patients except for iron and ferritin plasma levels which didn't change significantly in patients who had received blood. a positive significant correlation was established between crp and ferritin (r= . ) for patients under general anaesthesia, but not on epidural, regardless of the type of surgery. conclusions: iron and transferrin plasma levels fell acutely in surgical patients while ferritin and crp rose. transfusion implied an acute iron load.the established correlation between cpr and ferritin in patients on general anaesthesia suggests that ferritin behave as an acute phase reactant in that setting, while epidural anaesthesia may ameliorate the inflammatory response. objectives: to analize the effect of gastrointestinal complicacions (gic) related to the enteral nutrition (en) in the real volume of diet administered to icu adult patients. a prospective multicenter study was designed (comgine study) in wich en application, gic definition and his management were defined by collaborative consensus.patients treated with en in one month pedod were included. in each case, daily volume of diet prescribed (pv) and administered (av) was recorded and the volume ratio calculated (vr=pvxl /av). patients were divided for days of en according to the presence (group ) or absence (group ) of gic (abdominal distension, increase of gastdc residuals,vomits or regurgitation, diarrhea,constipation and bronchoaspiration). differences between groups were analized by anova and mann-whitney u test with p< . for statistical significance. (vr%) group (vr%) tolerance to the enteral nutrition (en) has been related to the severity of illness in icu patients. the aim of this study was to evaluate this relationship. methods. a prospective, multicenter, study was performed (comgine study) in wich en application and related gastrointestinal complications (gic) were defined by collaborative consensus. adult icu patients treated with en in one month pedod were included. gic were classified as: ) abdominal distension (abd), ) increase of gastdc residuals (igr), ) vomits (vom), ) diet regurgitation (reg), ) diarrhea (dia) and ) constipation (con). patients were divided in two groups: group a: patients with gic dudng their evolution. group b: patients without gic. differences between groups were analized for apache ii admission score or evolutive variables ( carbon dioxide production is a major determent of work of breathing. increase in co production during nutritional support may precipitate ventilatory failure and difficulty in weaning from mechanical ventilation. in the present study, co output was calculated while passive mechanically ventilated patient were fed with different amount of calories and different proportion of protein, carbohydrate and fat. four clinical stable and mechanically ventilated patients were studied. carbon dioxide was calculated while patients were paralyzed, sedated and mechanically ventilated. six nutritional regimens were used: a) no calories, b) t gr glucose/ h, c) calories equal to rest energy expenditure in special formula with low carbohydrates and high fat (pulmocare) d) calories equal to rest energy expenditure in standard formula (nutdson) e) calories double to rest energy expenditure in standard formula (nutrison) and f) calories equal to rest energy expenditure parenterel (tpn). carbon dioxide output was low while no calories and/or only gr/ h glucose was provided, the mean values of vco output were _+_ and !-_ ml/min respectively. there was no difference in vco output between with low carbohydrates and high fat regimen and standard regimen, mean values were t . -+ and _+ respectively.the high calories regimen and tpn resulted in higher vco output, mean values _+ and • respectively. we conclude that the special with low carbohydrates and high fat regimen did not reduce vco output, in the contrary, high calories intake as well as tpn increased vco output under tested conditions. klouche k., cristol j.p., vela c., canaud b., b raud j.j. m tabolic intensive care unit and nephrology department. lapeyronie hospital. montpeuier france. predictive factors for rhabdomyolysis (rh) -induced acute renal failure (arf) were studied in a retrospective study from january to january . patients (pts) (male: , female:lo; mean age: + y.o.) were admitted with rh defined as cpk> iu/ . etiologies were: traumatic and ischaemic , infectious , toxic , excess activity . factors studied were: simplified acute physiologic score (saps: . + . ), organ systemic failure (osf: . _-!- . ), diagnosis delay (d: +_ h), clinical parameters (sepsis, dehydration), blood chemistry data (cpk, bun, creatinine, potassium, phosphorus, calcium, proteins, hematocrit) and urinary ph. severity of rh was estimated by ward score determined according to phosphorus, albumin, potassium, cpk, dehydration and sepsis. urea appearance rate (uar) and creatinine index (ci*) were determined over a hours period. arf was observed in pts. in non-arf and arf groups respectively, saps ( . _+ . vs . + . ), deshydratation ( vs ), sepsis ( vs ), phosphorus ( . + . vs . -+ . ), calcium ( . + . vs . _+ . ), ward score ( _+ . vs . + . ) were significantly different. however, no significance was observed in uar ( -+ vs -+ ) and ci ( _+ vs _+ ). patients required hemodialysis (hd) ( : sessions) and remained dialysis free. only osf ( . _+ . vs . -+ . ), ward score ( . _-/- . vs . _+ . ) and ci ( +_ vs -+ ) appeared significantly higher in pts requiring hd. pts died from associated disease. all patients suffering from arf recovered a normal renal function. we confwmed that an elevated ward score (over ) is a good predictive index of arf. in addition we found that ci is a severity factor for arf requiring hd. thus, patients suffering for rh with elevated ward score and ci, have a fair chance of dialysis and should be treated more intensively. * ci (expressed in mg/kg) = (car + feces creatinine) / weight. where car: creatinine appearance rate; feces cr~t..= mean plasmatic creatinine x . . tr~er k., cetin t.e., tugtekin i., georgieff m., ensinger h. universit~tsklinik flir an~sthesiologie, uim, germany introduction: endogenous as well as exogenous adrenergic agonists have a profound effect on carbohydrate metabolism in human critical illness. in this study the effects of noradrenaline (nor) and dobutamine (dob) on carbohydrate metabolism during a hr infusion were investigated. methods: after approval by the local ethic committee healthy volunteers were studied. hepatic glucose production (hgp [mg/kg/min]), using , -d glucose as stable isotope tracer, as well as plasma concentrations of glucose (glc [mmol/i]) and lactate (lac [mmol/i]) were measured prior and during infusion of nor ( . pg/kg/min) and dob ( pg/kg/min). blood samples were drawn before and during the agonist infusion. results: no major changes in insulin and gtucagon plasma concentrations could be found during the study period. ::i:::: :iiiii~ ~ i ::i: ~:: : :: i:ii. mean-+sd are shown. # p< . , anova for repeated measurments. conclusions: the effect of nor on hgp and glc were smaller as compared to adrenaline (i) with a similar time course. in contrast to the effects of adrenaline and nor, dob had a different effect on carbohydrate metabolism: a decrease in hcp and glc, which is uncommon for a / -adrenoceptor agonist. since hgp is an energy consuming process that might deteriorate hepatic oxygen balance in critical illness, the differential effects of adrenergic agonists may be of importance and need further clarification. the nutritional insufficiency often accompanies post-operative hypercaloric states, inanition, serious infections and weakening chronic illnesses. that is why the early nutritional support, sufficient and appropriate for each individual base, is a fundamental component of intensive care unit as an indispensable factor for recovery. per this reason, our unit, developed a software for the implementation and nutritional control of t~e assisted patients. this software is incorporated is an expert system called ~i~su, designed and developed by the computational division of our unit. this system arrives to inferred diagnoses such as : respiratory, hepatic, renal(with and without dialysis) dysfunctions, pancreatitis, ards, decrease of consciousness, diabetes. according to these data objectives: to compare the effect of short term enteral feeding versus parenteral nutrition, when a isonitrogenous and isocaloric feeding solution is administered by either mute. methods: in a prospective controlled clinical trial patients were studied; all exhibited moderate degree of malnutrition, normal liver and kidneys, and a functi ning gastrointestinal tract. the patients were randomized to receive a free amino acid and small peptide diet ( patients) or an isonitrogenous isocaloric parenteral support (tpn) ( patients) (total energy: kcal, nitrogen: . g, carbohydrates: g, fat: g, n/non protein calories: / ) at least for days. results: there were no significant changes in anthropometric parameters within either group. nitrogen equilibrium was aqhieved by day in the tpn group and by day in the enteral group ( . % of the enterally fed patients and % of the tpn patients maintained in positive balance the day of the study). there were no significant changes in serum albumin within either group. serum level of transferrin reached a significant increase in both groups (p= . ). thyroxine-binding prealbnmin rose significantly in both groups as well (p= . and . respectively). statistically significant rises in lymphocyte counts (p= . and . respectively), in levels of c (p= . and . ) respectively), iga (p= . ), igg (p= . and . respectively) and igm (p= . ) occurred in either treatment group. there was a high incidence of negative skin tests at the start of the study in the enteral group ( . %) and the tpn group ( %). by the end of the study the incidence of negative responsiveness was . % and . % respectively. despite maintenance of similar glucose levels in both groups, tpn led to significantly higher serum insulin levels. the serum insulin increased almost linearly over the study period and eventually prevented fat mobilization and lipolysis, so that free fatty acid levels had fallen significantly. a significant elevation of the liver enzymes over the study period occurred in . % of the tpn group, but not in the enterany fed patients. conclusions: the present findings provide no evidence that enteral diets containing free amino acids and small peptides, as their nitrogen sources, are in any way inferior to isonitrogenous isoealoric regimes parenterally given. aim: the aim of this study is to describe and explore the expectations of the functions of the critical care nurse to enable the formulation of guidelines for the scope of practice for the critical care nurse with a south african context, methods: phase i was to determine the expectations of the critical care nurse, the nursing service managers and the doctors with regard to the functions of the critical care nurse. a focus group interview was held with a group of experts in the field of critical care. the results were used to compile a questionnaire. this questionnaire was sent to the critical care nurses, the nursing service managers and the doctors in south africa for completion. from these results the functions of the critical care nurse were determined. phase ii was to formulate guidelines for the scope of practice for the critical care nurse within a south african context. through usage of the date (phase i) the scope of practice was formulated. guidelines were formulated for the practise, education and research regarding the limitations of the professional-ethical authoration and the implementation of the scope of practice for the critical care nurse. objectives : high output gastric aspirates arc occasionally observed during fasting in critically ill paticnts, preventing any attempt of feeding via the enteral route. although these patients are often said to suffer from "gastroparesia", the motor correlates of this condition arc lurgcly unknown. in this stud?', wc recorded the gastrointestinal motility of critically ill patients with abundant (> ml/ hours) fasting gastric aspirates. methods : antral ( sites separated each other from . cm), duodenal ( site) and jejunal ( site) contractions were recorded simultaneously by ~eans of a multihimen tube assembly positioned trader fluoroscopic control (perfused catheter technique). tracings from prolonged recordings were obtained on a multichannel recorder ( a recorder, hewlett-packard) then anal) ,ed visually, with a special attention for the following abnormalities which are characteristic of intcstinal pseudoobstmctiou: l) absence or aberrant propagation of the migrating motor complex (mmc), ) presence of bursts (> min) of nonpropagated phasic pressure and ) presence of sustained (> min) uncnardinate pressure activity. patients with a volume of gastric aspirates of • (sd) [median ml/ hrs were investigated for - [median minutes. results : only one patient had no detectable motor abnormality. mmcs were either absent (n= ) or migrated abnormally (retrograde propagation : n= ; retrograde and stationnary : n= ) in pts. bursts of nonpropagated phasic pressure activity were present in the duodenum in pts and sustained uncoordinate pressure activity was found in pts. additional abnormalities included episodes of prominent pyloric activity. (n=l) and sustained antral pressure activity (n= }. conclusion : critically ill patients with large volume of gastric aspirates have manometric evidence of intestinal pseudoobstruction. prokinetic therapy in these patients should thus focus not only on enhancing gastric motility, but also on restoring a normal propagative contractile activity in the intestine. this prospective, open-label, randomized placebo-controlled study included patients with hypokalemia in whom rapid potassium replacement ( meq kci in h) was performed: patients received mg sulfate ( g in hours) and patients received a corresponding saline infusion. measurements were made at time , + , + and + hours results: k levels increased more in mg treated patients than in the patients who received saline infusion at time and h (p < . -students-newman-keuls). (table ). introduction. dual lumen uaso-gastrojcjunal tubes are a major ads'ance in nutritional therapy of mechanically ventilated critically ill patients since the " authorizc jejunal feeding with concurrent gastric decompression, there,, reducing the risk for aspiration. unfortunately, placcmem of these tubes in the jejunum regularly dictates to resort to endoscopy in order to facilitate pyloric intubation. recently, the remarkable gastrokinetic properties of the well known macrolide antibiotic er}lhromycin have been demonstrated in gastroparetic critically ill patients . aim. in the presem stu~,, we evaluated the feasibility of placing dual lumen naso-gastrojcjunal feeding tubes at the bedside without endoscopy, using edthromycin to help iranspy'loric migration of the tube under fluoroscopic control. methnd each patient admitted in our icu during a months period and requiring artificial ventilation and enteral nutrition for a period of at least days was included in the study.. after inserting the tube (stayput| sandoz, usa) in the gastric anmnn, e.rythromycin ( rag) was aduunistored intravenously, to help fluoroscopic positioning of the tube into the jejunum. the total duration of the procedure (from nasal intabatiun to jejunal placement), as well as the duration of ftuoroscopy were recorded in each patient. results. patients (male/female : / : mean age : . + . years; mean apacbell score : .t • . ) wore enrolled into the study.the procedure was performed within the dab,s following institution of mechanical ventilation. jejunal access was obtained in all patients without resort to enduscopy in , • . min.(total duration of the procedure). mean duration of fluoroscopy was . + . rain. conclusion. we conclude that placement of dual lmnen naso-gastrojejunal tubes can be obtained in mechanically ventilated critically ill patients without resort to endoscopy., provided that e rythromycin is used as gastrokinetic agent to help pyloric intubation. the following ad and dis parameters were considered in all patients: -mid arm circumference, triceps skinfold thickness, serum transferrin, albumine and lymphoeites and urinary creatinine/height index. patients whose results were bellow % of normal values in or more of the above criteria were considered undernourished (und).statistical analysis was performed using % analysis.statistical significance was established at p<o.o . results: a total of patients( female, male) -with a mortality rate (~) of , % -were studied, aged -+ years and a median ]enght of stay of days. -nourished (nou) at ad and at dis - ; ~ %; -nou at ad and und at dis - ; ) , % ; -und at ad and und at dis - ; ~ . %; -und at ad and nou at dis - ; ~ , %. we observed a p< . when we compared groups and (p= . ), and groups and (p= . ). variation in nutritional status and longht of stay: -nou at ad and nou at dis = > median lenght of stay days; und at ad and und at dis = > median lengbt of stay days; nutritional status and age at admission: -age > = years : nou ( ) , und ( ) -age < years: nou ( ), und ( ) nutritional status and age at discharge: -age > = years : nou ( ) , und ( ) -age < years: nou ( ), und ( ) we observed a p<o. when we compared groups and (p=o. ) and groups and (p = . ) conclusion: such study permits to conclude that most of our patients ( . %), staying in icu for more than days, were und, namely the elder. we observed that this kind ef patient had a longer median length of stay in icu, associated with higher mortality rate. in conclusion, the nutritional management is an essential element in suportive care of critical)y ill patients. ohiectives: sirs is associated with hypercataholisnl and resistance to nutritional support, despite raised circu&ting levels of growth hormone and insulin. serum igf- levels however are low; thercti~re rhigf-i administration might produce nsefnl anabolic effects. the pharmacokinetics of exogenously administration rhlge-i in such patients are likely to differ from that seen in the less seriously ill due to changes in circulating blood volume, increased capillary permeability, poor nutritional stares, and alterations in binding proteins. the ol jective of this study was to determine the clearance, apparent vohnne (if distribution (vd), time to peak concentration (tmax) and elimination half-like (tia) of a single subctkaneous il~ieetion of rhlgf-i in patients with sirs on the intensive care unit (icu). methods: icu patients with sirs were entered into the study, which had been approved by the ethics comjnittee. in each patient baseline hlood samples for circulating gf-i were obtained over a hour period, prior to il!iection of p.g/kg of rhlgf- subcutaneously. a further l samples were taken fi'om each subject over the next hours. circulating ige-i was measured in serum at each time point by radioimmtme assay, and the area under the curve tbllowing administration of rhlgf-i was derived tbr individual patients fixm~ baseline a~!justed igf-i levels. clearance values were caietdated by dividing the administered dose of rh[ge-[ by the total area under the etnve. vd and tv were calculated by regression analysis of the terminal part nf the log sertnn concentration time profiles. results: results are expressed as median (range). age ( - ) years, apache ii score ( - ), and length of icu stay ( - ) days. baseiine circulating igf- levels were low ( < - ) ng/ml reaching a peak of only ( < - ) ng/ml. of the patients had basal levels predmnhaantly below the inwel-limit of detection of the assay, and showed no appreciable rise in serum igf-[ levels tbllowing rhigf-i injection. parmacokinetic variables could not therefi)re be determined in these two patients. following rhlgf-i injection in the remaining patients tmax was at ( - ) hours, clearance was ( - ) ml/min, vd was . ( . - . ) l/kg, and tia . ( . - . ) honrs. conchlsions: there was marked patient wu-iability in response to rhlgf-i administration. vd was similar to that seen in poshq~erative maior surgery patients ( . vs . l/kg), but clearance was greater ( vs ml/min), tmax earlier ( vs hours) and t~a shorter ( . vs i . homts). if riaigp-i is to be administered to dtically ill patients the dose should he nlodified m the light of these findings. baekgronnd: acute bacterial endoearditis continues to be a condition with high morbidity and mortality. the majority of patients are treated with high dose antibiotics, but a patient group requires surgical treatment. methods and results: from january to march , patients underwent surgery for acute bacterial endocarditis: had native valve endocarditis and had prosthetic valve endocarditis. there were men and women. streptococcus viridans was the predominant infecting agent in native ~alve endocarditis and staphylococcus epidermidis in prosthetic valve endocarditis. progressive congestive failure, uncontrolled sepsis and peripheral emboli were the most common indication for surgery. although the mitral valve is more commonly involved in acute bacterial endocarditis, the aortic valve most often requires surgical inlervetion. the postoperative bleeding in the no-aprotinin group was + cc and in the aprotinin was :t: (p < , ). the mortality in icu was , %, the staphyloccocical endoearditis mortality was , % and the no-staphyloccocical endocarditis mortality was , % (p< , ). conclusions: the early surgery is indicated if endocarditis has no response with medical treatment. the mortality of staphyloceocical endoearditis involving left valves was higher than caused by other infecting agents. aprotinin treatment improved prosta#andin metabolism and preserved pletelet function during open heart surgery and could be useful in this type of interventions. urgent surgery had a high mortality ( %). selective digestive decontamination (sdd) has increasingly become the subject of critical discussion sine~ the development of multiresistant organisms has become an issue. moreover, a selection of gram-positive pathogens must also be taken into account when using the sdd regimen, which is primarily directed at the gramnegative bacterial specumn, with the methicillin-resistant staphylococcus aureus strains (mrsa) being of particular importance. the objective of our study was to determine the extent to which colonization with mrsa strains is promoted by sdd. method: patients (ventilation period > days) were randomized and allocated to the sdd group (n= ) or the control group (n= ). in their general intensive care theraw, there were no differences between the groups. the sdd regimen consisted of the four times daily administration of rag polymi~ mg tobramycin and mg amphotericin b in the nesc, mnoth and stomach. systemic prophylactic ~dmini~/rution of antibiotics was not part of the sdd regimen. smears were taken from the nose and the rectum twice wceldy and from the pharynx and trachea once wceldy, and tested for mrsa. further samples were taken as clinically reqnircr results: smears were examined in the sdd group. mrsa strains were detected in samples ( . %) from patients, and in patients they were detected for a period of up to weeks. the positive smears were districted as follows: tracheal / ( . %), nasal / ( . %), pharyngeal / ( . %) and rectal ( . %). severe mrsa-induced infections were observed in patients (infection rate . % of the colonized sdd patients). smears were examined in the control group. ivlrsa swains were r in samples ( . %) from patients, but only repeatedly over a period of up to days in patients. the po~tive snmars were distributed as follows: traclmal / ( . %), nasal / ( . %), pharyngeal / ( . %) and rectal / ( . %). there were no mrsa infections in the control group. conclusion: the data collected support the view that the use of sdd promotes a selection and persistence of mrsa strains. longer-term colonization with mrsa and sovere systemic inf~ons were only found in the sdd group. although the clinical and epidemiological impact of resistance develol~ng when sdd is applied ~maine unclear, this question should be given close scrutiny. tazobactam/piperacillin (taz/p p) is a new broad spectrum antibiotic, in which the acylaminopenicillin piperaeillin is protected by the betatactamase inhibitor tazobactam from hydrolization by bacterial enzymes. taz/pip has shown to possess a high antibacterial activity against almost all clinically relevant bacteria and is a registered drug in germany. obiectives: purpose of this investigation was to evaluate, whether faz/pip . g is suited for efficient antibacterial monotherapy of severe infections and what influence dosage frequency reveals on clinical efficacy. methods: hospitalized patients have been documented in this multicenter trial during a year period. as this investigation should reflect the usual clinical treatment, the only criteria for enrolment were the typical signs of infection as e.g. temperature > ~ leucocytosis or an isolated pathogen. exclusion criteria did not exist and the patients were treated in accordance to the severeness of infection, underlying diseases, risk factors etc. with taz/pip . g t.i.d, or b.i.d. results: patients suffered in most cases from infections of the lower respiratory tract (n= ), followed by intraabdominal (n= ) and skin and soft tissue infections (n= ). % of the lrtis wvre nosocomial acquired and in % the treatment was conducted as monotherapy. in % the lrti was treated with taz/pip b.i.d, and in % t.i.d. pseudomonas spp. (n= ) and staph..aureus (n= ) were the most isolated pathogens pretrcatment. the clinical response rates (cured/improved) after treatment with taz/pip . g b.i.d, and t.i.d, were % and % respectively. results for intraabdominal-and skin and soft tissue infections will be presented. conclusions: in hospitalized patients with severe infections successful treatment with taz/pip in monotherapy is possible. in this population a reduction of the dosage frequency to . g b.i.d, revealed equivalent clinical response rates. objectives. retrospective evaluation of cases of severe generalized tetanus (sgt), treated in our icu the last years. we review cases of sgt ( m, f), mean age . years. in eases the entry site of c.tetanus was a skin laceration, in case it proved to be the external genitalia, while in the rest no portal of entry could be determined. in the first cases incubation period was short ( - days) and so was the period of onset ( - days). all patients needed mechanical ventilation (range - days), initally through an orotracheal tube,and later through a tracheostomy, performed • days after admission. clinical manifestations of sgt included muscle rigidity and i generalized spasms, persisting for up to weeks in the most severe cases. significant autonomic nervous system dysfunction was present in cases occurring - days after the admission and following the time course of generalized spasm. besides general supportive measures, specific treatment included passive +active immunization, penicillin g, magnesium sulphate and sedation in a variety of regimens. neuromuscular blockade was required in cases. nosocomial infections occurred in eases, with sepsis and mof in one. average stay in the icu was - days. one patient died with severe septic complications and one was discharged with severe disability due to anoxaemie ancephalopathy, after a cardiac arrest on admission. ~ disinfectant in suspension test, without presence of organic load, disinfectants showed efficacy on lm. in the carrier test, in the presence of organic load, out of examined disinfectants did not exposed efficacy on lm. the results of examinations clearly showed that evaluation of disinfectant's efficacy partly depend on the used test method. antun basi , intensive care unit, kb firule split spin~ideva ! jugoslavia bacteremia and sepsis are frequent complications encouuntered in severe icu patients.microorganism identification with hemoculture presents the basis for adequate and successful antibiotic treatment.in many patients damage and vulnerability of the peripheral veins presents an obstacle for obtaining the blood culture from the central venous (cv) catheter sample could be also used. material and methods blood cultures were perfomed in lo patients on blood samples simultaneously obtained from the peripheral vein and cv catheter three times in a -hour period.criteria for the suspected bacteremia were body temperature above c and leucocytosis above ioooo leucocytes/dl. the site for venipuncture and the cv catheter stopcock port were cleansed with povidon iodine.after the initial ml of blood were discarded,lo ml were used for the blood culture.standard laboratory technique for blood cultures was used. results and discussion in ( %) patients hemocultures was negative at both sites,whereas in the remaining ( %) they were positive.for twentyone ( ~ of the positive patients the same results were obtained at both sites (peripheral vein and cv catheter),whereas in ( . %) patients the blood culture were positive only for the cv catheter samples.the cv catheters were in place for less than days in patients and for more than days in patients.from patients with positive blood culture from the cv catheter,one patient had the catheter for three days,whereas the other had the catheter from - o days. we neither found significant differences in hemodynamic dates : objectives: , to count and evaluate bacteria isolated from endotracheal (et) suctiori samples (with and without saline). . to establish the exogenous source(s) of pathogens isolated from carer's hands and the equipment involved in sampling in order to reduce the incidence of contamination and infection. method~: this prospective study included consecutive ventilated patients ( male and female, _ + yr; apache ii score -+ ) over a period of months. et aspirated samples with and without saline were taken daily from day of intubation until pathogen~ were presented in counts of _> per ml. at the same time, samples from both carer's hands were taken before and after et suction and a swab from the ventilator tube. results: the overall length of intubation varied between to days. bacterial transfer between staff and patients was noted in % of patients until day of intubation. there was no significant correlation between severity score and appearance of colonization. the incidence of pneumonia in studied patients was % with an overall mortality rate of %. acinetobacter anitratas (no ), staphylococcus aureus (no. ), klebsiella pna~moniae (no. ) and pscudomonas aeruginosa (no. ) isolates predominated in all our specimens. we noticed increased resistance to most antibiotics with the exception of imipenem for gram (-) bacteria and vancornycin for gram (+) bacteria. conclusions: i. tracheobronchial colonization appears directly in the maiority of intubated patients. . there is a close relationship between the microflora of personnel, patients and equipment. . bacteria transfer was noted both to and from patients. . strict hand disinfection policy remains an important measure for the proper care of mechanically ventilated patients to reduce respiratory infections. nnseeomial pneumonia is the most common nnsocomiai infection in the icu-settiag, reported in up to % of patients admitted to the icu following surgery. it is associated with significant mortality that ranges from ~ to %. enteric gram-negative bacilli have been implicated in % to % of ventilntor-associated pneumonias and pseudomonas aeruginosa accounts for % to % of these pneumonias. importantly, epidemics of/ - actamnse-pruducing enterobacter spp or klebsiella spp that are resistant to extended spectrum cephalosporins or penicillins, pose serious obstacles to effective antibiotic choices. carbapenems provide in ~tro activity against a wide range of enterobacteriaceaeand other gramnegative aerobic bacteria, except steaotrophomonns maltophilia. in vitro meropcnem is more active against pseudomonas spp than imipanem (especially p. aeruginosa and p. cepacia), imipenem and meropenem are effective against more than % of strains responsible for nnsocomial infections. all major pathogens associated with lrti are usually covered by the carbapenems, exceptions are pathogens involved in so-called atypical pneuomouia like mycoplasma, chlamydia and legionella. carbapenems are highly stable in the presence of most chromsomal and plasmid-mediated blactumases and usually offer a postantibiotie effect lasting for three hours against most of the enterubacteriaceae. reeent studies comparing imipenem/cilastatin with other ~-lactams and fluoroquinolones in severe lrti in icu patients resulted in favourable clinical cure rates and good tolerance, but development of resistance in p. aeruginosa and ;. aureus during treatment were of some concern. meropenem offers the advantage of greater stability against enzymatic degradation, so no concomitant administration of an enzyme inhibitor is necessary, and meropenem appears to be associated with a lower risk of seizures, particularly when used at high doses. results from studies with meropenem in lrti, especially in critically ill patients with acute exacerbations of chronic bronchitis, demonstrated excellent cure rates and better gastrointestinal tolerance of this new carbapenem. both earbapenems are effective candidates for use as empiric monotherapy in nosucominl infections of critically ill patients. qbl~ctives a favourable effect of iv immunoglobulins in septic surgical patients has been reported, but not sufficiently validated. we conducted this study on trauma patients to: i) investigate the effect of ivig on septic complications and il) quantify this effect by means of serum bactericidai activity (sba) assessment and iii) to explore the effect of temperature increase (from to ~ c) on the sba methods: twenty trauma patierits matched on admission for age, sex, inju~ severity score and glasgow coma scale, were allocated to receive either wig (ivig group; i patients) or equal volumes of human albumin % (control group; patients). wig (sandoglobulin) was administered in a total dose of g/kg divided in a four time regimen on days , , and post-admission. three blood collections were performe& before the first dose (day ) and hours after the third and the fourth dose (days and respectively). complement, lgg fractions, the sba at ~ and at o c and clinical parameters were recorded. results-similar lgg and igg] serum levels were found in groups ivig and control on day ( +_ vs • ns and + vs + , ns), whereas they were significantly higher (p< ) in the v g group on days ( _+_ vs + , p< ) and ( _+ vs +i , p< . ). the various complement-fractions increased in both groups without inter-group differences the mean (• sbas ( ~ c) at rain in ivig group vs control group were: - _+ vs - • ns for day , _+ vs - _+ p< for day and _+ vs - + p< for day . the mean (+sd) sbas ( ~ c) at rain presented a significant improvement over those of ~ c but for the control group remained negative a~d were respectively as following: -~ • vs - + , ns for day , +_ vs - _+ , p< . for day and _+ vs - _+ , p< . for day . the increase of temperature induced a -fold improvement of sba in iv g group and -fold ofcontrol-~oup positive blood cultures, and the product of the infectious episodes number multiplied by days of occurence, were significantly lower (p< ) in the ivig group than in the control ( vs , and vs , respectively). conclusions: our study shows a significantly favourable effect of ivig administration on septic complications and on sba of trauma patients. the increase of temperature results in a significant improvement of sba of patients that received ivig, which theoretically means a farther prevention of infection in the febrile state. pharmaceutical microbiology, university of bonn, meckanheimer aune , d- bonn, germany infectious diseases in intensive care patients are common in comparison to patients on other wards and out-patients. the main difference is that intensive care patients are much more sensitive even to less virulent bacteria. thus, the spectrum of infecting organisms is different. strains often regarded as pathogens with low virulence cause serious infections in these patients. strains such as serratia, however, have intrinsic resistance to most commonly used agents such as rd generation eephalosporins. furthermore, the common pathogens like staphylococci, psoudomonas aeruginosu, enterocneei and gram-negative bacteria, enterobacteriaeceae as well as the non-fermenters are less sensitive if isolated from intensive care patients. it is difficult to generalize on intensive care units as different patient groups are in different icus aud there are great changes from one hospital to another and from one country to another. if we take s. aurens strains from one study from the'overall resistance in intensive care units towards oftoxacin was %, whereas in other hospital wards the percentage of resistance was . %, in out-patients, however, only .$ %. the same trend was true for entercnecus faecnlis, coagulase-negntive staphylococci, and other bacteria as well as other drugs. one most striking difference was found with klebsialla pneumoniae and gantamycin resistance, which was $ times higher in intensive care units as compared with outpatients, whereas in the same species no difference was to be seen with the resistance towards carbapenems. however, differences between countries seem to be even more striking, as example gantamycin resistance and staph. anrens is given. the extreme difference is more than fold. thus, it is evident that there is a general trend towards higher resistance in intensive care units, but no generalizatiouis possible. therefore, surveillance studies in intensive care units are needed and the antibiotic policy has to be adapted to the specific needs of the unit. in the icu setting the most potent antimicrobial agents are required to address problem organisms including those resistant to penicillins, cephalosporins and aminoglycosides. carbapanems would appear to present a useful option in this setting. objectives of this study was the evaluation of systemic candid• in postoperative cardiac surgery patients (pts) with prolonged icu stay. methods: out of postoperative adults pts of mean age . + . years old, with a mean icu stay of . _+ . days, following an open heart surgery from july to april , pts ( %) remained in icu for more than days because of severe perioperative complications. patients were included in the protocol if they had clinical signs of infection or sepsis, and fungi isolated in blood culture or in culture from at least three different sites. the patients who developed systemic candidiasis received iv fluconazole ( mg/day) ( patients) or amphotericin-b for at least four weeks, and then they were closely monitored. results: out of postoperative pts with prolonged jcu stay, pts ( . %) developed systemic candid• usually after the th postoperative day. they were males and females of mean age +_ . years old. this group of pts had prolonged bypass and aortic cross-clamp time compared to control group ( min vs , and vs min). all these pts received inotropes per• (mean value= . ). during their icu stay, pts developed sepsis of bacterial origin, while the other two severe infection, and received antibiotic regimens for prolonged period. the patients were submitted to mechanical ventilation for a median period of days. the median icu and hospital stay was and days respectively. all pts have been improved and finally negative cultures were obtained. conclusions: . a significant percentage of patients who remained in the postoperative icu for more than days developed systemic candidiasis. . all patients who developed systemic candidiasis had received antibiotics because of sepsis or severe infection, for prolonged period. . fluconazole seems to be a very good alternative to amphotericin-b. . fluconazole is a safe antifungal agent with few side effects. botulism is the most severe and an odd food poisoning. although it is more commonly related to preserved meat derivatives, preserved fish and vegetables are also responsible for a number of cases. obiectives: to evaluate four familiar outbreaks of botulism . methods: we study the patients that were admitted in our hospital because of botulism from may to february . results: the thirteen pacients involved had a previous history of home preserved beans ingestion. after a -hours incubation period, gastrointestinal symptoms (abdominal pain, vomits, constipation) appeared and lead them to hospital consultation in the th to th day after ingestion. two patients died (acute respiratory failure before admission), seven were admitted in icu, two in ward and two of them were discharged from emergency room. clinical symptoms and the previous history of the ingestion established the diagnosis, that was emg confirmed. in all cases, symptoms were consistent with b-toxin botulism. b-toxin was isolated in serum and food proceeding from the third outbreak, and the serum was negative in the other ones. neurological symptoms were predominant: midriasis ( %), dry mouth ( %), dysfagia ( %), asthenia ( %), palpebral ptosis ( %), accomodation paralisis ( %) and urinary retention ( %). muscle weakness lead to acute respiratory failure in three patients (one of them required mechanical ventilation). four patiens developed infections (respiratory, urinary and phlebitis). both died patients and one another presented severe hypertension. all admitted patients were treated with polivalent anti-toxin. the two patients who underwent a more severe muscle weakness received also guanidine hydrochloride, with no answer in one case and provoquing a cholinergic crisis in the other one. icu length of stay was days. at hospital discharge, patients continued symptomatic, mainly with dry mouth, disfagia and impaired vision. conclusions: although botulism is a serious illness, the pronostic seems favorable if treatment and support measures are avaible. usually neurological symptoms we predominant and at discharge some of them could still persist. the arrow "hands-off" (aho) thermodilution catheter (tc) is completely shielded during balloon testing, preparation, and the insertion procedure. in order to assess the value of the aho thermodilution catheter in the prevention of systemic infections associated with pulmonary artery catheterization (siapa), we conducted a randomized prospective study over an -month period. methods : the patients (pts) were randomly assigned to two groups : group i for a standard tc customarily used in the department, versus group for the aho thermodilution catheter. the diagnosis of siapa was determined on the basis of a positive culture of tc and bacteremia with the same organism, with out any other nearby focus, in association with regression or disappearance of the clinical signs of infection after removal of the thermodilution catheter. results ( objectives: the mortality rate (mr) of tb requiring mechanical ventilation (mv) is high ( - %). the aim of the study was to evaluate mr, associated factors, and prognostic significance of mv and hemodynamic disorders from tb in icu in patients with tb. methods: clinical parameters on admission, and complications in icu were related by univariate analysis to icu, hospital, and month outcome. patients required mv; were immunocompromised (ic) including hiv. tb was pleuropulmonary in , disseminated in and meningeal in . results: mr was % in icu, % in hospital and % at month. / ( %) < . mortality was associated with a high saps score, initial shock, mv and nosocomial septicemia. the mr dramatically increased when ards occurred during illness, despite the lack of correlation between mr and initial po /fio ratio or initial murray score. the site of infection did not influence the mr. surprisingly, the mean therapy delay was shorter for non survivors. mr was not related to ic status, nor hivstatus, but was only related to previous steroid therapy. conclusion: mr of tb requiring icu is high ( % at month). need for mv increased mortality ( % vs %). general severity and respiratory dysfunction seem to be major prognostic factors in icu rather than tb per se or than therapy delay. in spite of the improvement in the prognosis of pneumococcal meningitis (pm) with third generation cephalosporins (tgc), this infection still presents a great mortality which could be increased with the appearance of antibiotic resistant streptococcus pneumoniae. objectives: to asses intensive care mortality and morbidity of pm and to define patients (pts) at risk of complicated evolution. patients and methods: a retrospective evaluation of pm cases (all diagnosed by csf culture) admitted in our icu from january tit march . in all pts we analized: demographic data, underlying disease, apache ii score, clinical symtomps, treatment, complications and outcome. statistical analysis was done using bmdp sofware package. results:a total f pts were studied, males; mean age , _+ ( - ); apache ii score , + , ; glasgow coma scale (gcs) at admission , _+ , ; ( %) pts suffer from cronic pathology; ( %) pts diabetes mellitus (dm), ( , %) pts had had a previous cranial traumatism. in cases the source of infection was otic and also in ( %) episodes of pm there were bacteriemia. in out of ( %) pts that ct was performed no radiologic abnormalities were shown, of them presented cerebral oedema and pts a cerebral abscess. twenty-eight percent presented seixures, % hemiparesia, , % respiratory failure, , % shock, i % renal failure, , % multiple organ failure (mof). as for treatment refers , % pts recieved only penicillin, , % pts only tcg, , % pts tcg followed by penicillin and , % pts tcg+vancomycin. seventy-five percelat of pts recieved corticosteroids and , % vasoaetive drugs. the mean icu stay was , : days ( - ). twelve ( , %) pts died, two of them presented pm relapse (resistant streptococcus pneumoniae) and another two pts developed neurological sequelae. factors associated statistically with bad prognosis were dm, the use of vasoactive drugs, shock, mof, the apache ii score at admission, the gcs at the and hours from admission in the icu but not the gcs at admission. didn't resulted statistiealy signifcative age, previous eronie pathology, seizures, baeteriemia, renal failure and coagulation disorders. conclusions: mortality was high and associated to apache ii score at admission, to gcs at and hours after admission, shock, vasoaetive drugs and mof. objectives:the aim of the study was to analyse some of significant immunologycai changes in surgical patients,requiring intensive health care,and to determinate the possibility for evaluation,dynamical examination and importance of immunologycal problems for treatment. methodes:the study concerns a number of patients with expanded surgical intervention or serious postoperative complications.the results has been carried out with fiowcytometryc analyses of lymphocytic suhpopulations and routins methods for investigation of humeral immunity.the"panel" for evaluation of (} immunologycal parameters has been offered:t-calls total/cd +/;t-helper/cd +/;t-supressor/cd +/ th/ts ratio;b-cells/cd +/;naturai kilier/nk/cells;skin test for cellular immune function;phagocytic and oxidative activity;serum levels of immunogiobulins-g ,a,m;protease inhibitors;c-reactive protein.all patients have been studied during suffering and after surgical procedures dynamicaly. results:there have been estimated significant changes in immunologycal parameters especially:decrease of t-cells: cd +mean= . %/ . %- . %/and cd +mean= . %/ % - . %/;inverted th/ts ratio ,mean=o. / . - , /;reduced or negative skin teste;reduced phagocytic and oxidative activity before septic complications. conclusions:dynamical examination of immunologycal parameters shows,that the prolonged t-total,t-helper lymphocytopenia with functional deficience of ceils-mediated immunity correlates with the stage of clinical condition of the patients and has prognostic importance.it's clear,that immunologycal monitoring gives a possibility for immunecorrection. patients (pts) with the human tmunodeficiency virus (hiv) infection have a decreased immune response and are particularly susceptible to infectious endocarditis (ie). the aim of our study was to analyze the prevalence of ie, its clinical and therapeutic implications in a hiv population we prospectively studied pts, . % ( / -group ie+) with ie during the clinical course of this disease. we analyzed the following parameters: age, gender, race, type of hiv, cdc classification, number of t and t type cell population and its ratio, therapeutic with azt, type and number of opportunist infections (inf, mycobacteriosis (mb), neoplasm's (nee) the echocardiographic parameters were lv internal diastolic and systolic diameters, lv percentage of fractional shortening, interventricular and posterior wall thickness, the degree of valvular regurgitations and the presence of pericardial effusion. el was located at the mv in . %, tv in . %, av in % and pv in . ~ and was multiple in . %. hiv el+ pts had larger lv diameters and more frequent significant valvular regurgitations ( % tr, pe %, mortality %). these two groups differed significantly in the following clinical parameters: the typical symptoms were watery diarrhea, high fever, tachycardia,luekocytopenia and oligouria within th postoperative days. the patients with mrsa enterocolitis had positive mrsa culture from the many materials except feces.mesa strains frequently had coagulase type ,enterotoxin a and toxic shock syndrome toxin- .eight of patients had postoperative organ failure.most of the mrsa strains in japan were similar in coagulase type to our hospital and our department.all of mesa strains were susceptible to vancomycin and arbekacin,tbough most of them showed resistant to many other antibiotics.we have employed guidelines for therapies such as oral or enteral administration of vancomycin and correction of the hemodynamics for dehydration and circulatory failure due to diarrhea from .futhermore we have placed colonized or infected patients in private room,worn gown and mask,and carefully washed our hands from . these countermeasures for prevention of nosocomial infections after significantly reduced the incidence of mrsa enterocolitis. conclusions:earlier diagnosis and treatment, and distric prophylactic measureres against mrsa infections are very important. -- cdo ivda leptespiresls affects all the organs with widespread hemorrhage that is more prominent in skin, mucosa, skeletat muscles, liver and kidneys. lung involvement is usually mild and less common. suli, it is very uncommon acute respiratory failure to be the pr sontirlg symptom. a case with leptosplrosl..,s which was presenting with acute respiratory failure is described. a year-old man admitted to icu becauso of fever, myaigla, aevere c~, hemopty~s. his blood gases showed: pao : mmhg with fio : . , pco : mmhg, ph: . , hco : mecl chest x-ray film demonstrated diffuse bilateral alveolar pattern occupying beth lung / ). trarmamlnase, bllllrubln, ~ and esr were elevated, wbc was . mm , platelet: . ram , hematesrlt: %, hemoglobin: .sgrldl=. there was no clinical or ecttlographlc evidence of left heart failure.patient fulfilled the criteria for diagnosis ards he was found to have an ~lutinatlon tlter for leptoq~lral antigens(indirect he~lutlnatlon atomy, ilia} very high ( / , negative<ill ) and iglm antibodies also very high (elisa, a= . , negative< . ) strongly suggesting leptospirosls. treatment with tetracycline and non-tnvaslve mechanical ventilation by nasal mask were started. pre~jre support mode and cpap was usod. the following days the clinical picture,the oxygenation and the chest x-ray of the patients were improved, and patient dl~herged from the icu. the control of leptosplremlc phase as well as his good cooperation during nipsv contributed to rapid recovery and excellent outcome in hiv infections, pneumonias (pnm), mainly due to pne~ mocystis carinii (pc) have an outstanding place in pu ! monary complications. the aim of this work was to compare two group> of patients admitted with pnm in our icu during the same period ( - ): group a, patients hiv+, and group b, patients hiv-. apache ii was identical in the groups (p=ns). group a required more often mechanical ventilation (p= ,o ), had a higher p(a-a)o (p= , ) and metabolic acidosis was more frequent (p= , ). regarding laboratorial parameters group a had a lower no. of linfocytes (p= , ), a higher ldh (p= , ) and a more marked hypoalbuminemia (p=o, ). mortality was higer in group a ( , %) than in group b ( , %), (p= , ). analysing the a group patients, we found no significant differences between alive and deceased patients, with exception for albuminemia, which was lower in the deceased patients (p= , ). in conclusion, the hiv+ patient's pnm have a more agres sive behavior when compared with community acquired hiv-patient's pnm. the prognosis was not influenced by the apache ii. perhaps other parameters such as p(a-a)o , metabolic acidosis, linfocytes, ldh and albumin shoud be more evaluated as possible predictive indices. some prognostic factors, usually accepted as predictive in the analysis of hiv+ patients do not seem to be worth in the late stages of aids, mainly when they reqquire intensive care. intensive care unit, onassis cardiac surgery center, athens, greece. objectives of this study was the comparison of two different antibiotic regimens as prophylaxis in cardiac surgery patients. methods: in a prospective randomised comparative study, two different forms of antibiotic regimens were investigated : a single dose of cefuroxime (zinacef, gr) (group a) given during the induction of anaesthesia, versus a four days combination of amoxiculine (amoxil, gr tid) plus netilmicin (netromycin, mg bid) (group b). a total of patients (pts) ( males and females, of mean age . + . years old) were included in the study over a period of one year; in group a and in the group b. patients were checked for the occurrence of infection during the first postoperative month. results: the total rate of infection in cardiac surgery pts was . %; . % in group a and . % in group b (p=ns). pts ( . %) developed infection following cabg, pts ( . %) following valve replacement and pts ( . %) after other cardiac surgery. they were males ( . %) and females ( . %). endocarditis has occurred . % in group a and . % in group b. severe wound infection was recorded in . % in group a and in . % in group b. one case of sepsis ( . %) in group a and in group b ( . %). respiratory infection occurred in pts of group a ( . %) and in pts of group b ( . %). two cases of urinary tract infection was in group a and one in group b. catheterrelated infection was occurred in ( . %) in group a and ( . %) pts in group b. pts ( . %) had fever of unclear aetiology in group b. conclusions: there was no statistically significant difference regarding the rate of infection in both groups. a single dose administration of cefuroxime is accordingly just as effective as a four days regimen of amoxicilline plus netiimicin. legionella pneumophila is a common bacteria of the environment, and it is an agent responsible for severe community acquired pneumonia (cap). we analyzed the patients with lpp admitted in our icu during the last years ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . they represented . % of cap. seven patients were males and female, with mean age . + . years. tiss was . + . and apache ii . + . . all, but patient, were under mechanical yen tilation (mv) during a mean period of . • (min-l, max- ) days. two pneumonias occurred beyond the season, while patients had an epidemiological history. only patient had no risk factor. in all the others tobacco smoking and alcohol abuse was quite frequent. diagnosis was based on serologic test and culture or direct fluorescent antibody staining of bronchial secretions. seven patients had a multisystemic disease with hepatic dysfunction in , renal failure in (due to rhabdomy~ lysis in ). one patient had a prosthetic valve endocarditis and another developped ards. nosocomial septicaemie occurred in patients. mortality rate was %. deceased patients had initially higher apache ii, (a-a) , and lower natriemia. comparing lpp with the other cap (n= ), both submitted to mv, mortality rate was similar ( , % versus . %). in conclusion lpp can occur all over the year. there was a high incidence of severe complications and outcome was similar to the other cap when requiring mv. prospective specimen brash (psb) with culture > cfu cfu/ml. broncho-alv~lat lavage (bal) ~= c'fu/rnl or positive blood culture. were excluded for rapture of treatment ; were analysed (shift with oral antibiotic : ; prohibited antibiotics associations : ; resistant germ : ). clinical data : age , • , ; saps • , ; mac cabe i : , % -ii : , % -iii : , . , % of the patients were intubated and under mechanical ventilation. the pneumoaiae were : primitive in ( , %), copd ( , %), aspiration pneumonia ( , %). germs were isolated (psb , bal , blood culture ) : s. pneumoniac ( , %), h. influeazae ( , %), sttep~:occns ( , %), saar ns ( , %), enterobaetdrindr ( , %), mosexella catarrhalis ( , %), othem . / ( , %) were sensitive to freatment. the ltentment was mg/kg/d of ampiclllin and mg/kg/d of sulbactam in continuous iv adminisu'ation during at least days. clinical eff~ienev : success ( %), failures ( %) with superinfeetion , worsening or relapse , dead , side effects . there was no difference between etiologies : primiti~;e~ , %, copd , %, aspiration pneamoniae , %. the bacteriological effieieacy was evaluated only for patients with eradication ( , %), eradication but super~ection ( , %) : with pseadomoaas a&ogiuosa , eater~ac~ ; beeteriological failure ( , %). in conclusion, the aasor ampicillin -sulbactam is effective for the i~eatment of severe acquired community pneumonise. objectives : to assess the efficacy of chlorhexidine (cl) gel or suspension applied in the nose and in the op for the prevention of the tmcheobronchial colonization. methods : thirty-seven patients expected to be intubated for > h were randomized to received topical application oga cl suspension ( %) qshrs, a cl gel ( %) q hrs or a placebo. in addition all vpts received a nasal and a op spray ( %) of either cl or placebo administrated according to the same schedule. semi-quantitative cultures of the anterior nares, the oropharynx (op) and the trachea were obtained on admission and once a day until extubation (just before the next application). the results were assessed according to the following criteria: success = no acquisition of gnb in the trachea ; failure = acquisition of gnb in the trachea. acquisition was defined by a follow-up culture positive for a gnb not present in the trachea on admission. results : success failure nosocomialpneumonia overall morality clsusp. placebo clgel placebo n= n= n= n= / / / * / / / / * / / / / / / / / / i *p = , byfisher'sexacttest conclusions : these results suggest that topical cl gel administered q hrs may prevent tracheal colonization by gnb. f. daumal*, m. daumal**, c. plot**, v. vurmmen ~ e.colpurt**, b. manonry** * hygiene hospitali&e, ** service de r enmmtion, * service des admissiens-urgeuces centre hospitalier g- ndral - saint-quentin -france obiectives: evaluate the nosocemial risk due to peripheral venous inserted short catheters, and the quality of care. patients-methods: the intensive tare unit (i.c.u.) is a beds unit. the prospective study includes all the patients comn~ in from / / to / / . the recruitemont uses an evaluation schedule of local clinical signs. the nurses aimed to create this evaluation data which includes the place of entry site, the duration of catheterization and the cause ot withdrawal. only patients staying longer than days in the i.c.u. are accounted for. the diagnosis of uosoenmial infection is assured by the physician taking care of the patient and by the hospital epidemiologist on the next signs: evident pus at the catheter entry site, positive culture of the strain, with or without the same pathogen in the blood sla'uam,the patient having no other distant source of infection. analyses were performed on epi/nfo. results: the occurrence of nosoeomjal inthrtions: i abcess and bacteremia during the first part of the study lent the medical staff to modify the protocol of insertion end survey of the device. so we analysed different periods: period ( / / to / / ) and period ( / / to / / ) for all .e peripheral catheters inserted in the i.c.u. period , % , % en infection due to peripheral venous device is a daily threat. the severity of some clinical situations requiring admission in icu proves it. the motivation of nurses for rigid adherence to established protocol, the daily survey of the entry site, the withdrawal of the peripheral catheter every hours aimed to reduce significantly the local signs of inflammation end infection of peripheral catheters inserted inside the i.c.u. objectives: to investigate the use of a new metabolic monitoring device for different ips levels by comparing oxygen consumption (vo ) to measurements of the mechanical work of breathing (web) and p . . methods: the study was approved by the institutiotml ethics committee. eight patients were investigated during weaning after prolonged mechanical ventilation ( - days) for various diagnoses when the clinical physician judged the patient to be ready fur weainag. ips was setto , , , mbar far rain periods each. all patients had a peep between - mbar.. respiratory frequency (f), tidal volume (tv), minute ventilation (ve) were read from the ventilator display ( ae, puritan bennett, carlsbad, usa). flow and airway pressure were measured at the endotracheal tube site. esophageal pressure was measured using an esophageal balloon catheter (fa. ruesch, frg). web was determined as the area subtended by the pleural-pressure-vohime curve. p . was determined by using standard occlusion technique and graphical analysis of the airway pressure tracing. vo and vco were measured using the pb metabolic monitor (puritan bennett, carlsbad, usa) connected to the pb ae ventilator. all data are given as mean• deviation for each ips level. comparison between the different ips levels was performed using anova for repeated measurements. significance was considered at p< . , compared to ips mbar. results: the values for breathing pattern, web, p . , vo and vco are given in the table for the different ips levels; significance is indicated by ~. objectives: fluidized beds are often used in the management of critically ill mechanically ventilated patients. critically ill patients are increasingly colonized with resistent pathogens [ie: p. aeruginosa, methicillinresistent s. aureus (mrsa), extended spectrum i~-iactamase producing enterobacteriaceae ] that can ultimately cause nosocomial infection. methods: we prospectively monitored bacterial colonization of mechanically ventilated patients and of the fluidized bed (clinitron) inwhich they were treated. multiple samples for quantitative bacterial cultures were taken from oropharynx, trachea, feces and bedsores. samples of ceramic beads from the bed were also taken both during and after patient stay (after bed operation in the absence of patient). re,~ults: episodes in consecutive patients (mean age: . years) were analyzed. all had bedsores and/or urinary catheters and fecal incontinence, patients had nosocomial pneumonia, had urinary tract infection [ with extended spectrum imactamase producing k/ebsie//a pneumoniae (ki~lse)], one had positive blood cultures with mrsa, and one patient had a ki~lse found in high concentrations ( - s cfu/ml) in occasions in feces. patients were heavily colonized: the , samples from ceramic beads showed no growth or became sterile without any sterilisation procedure (even in one case of presence of kf~lse) during the patient stay. conclusions: fluidized beds do not put patients at high risk of acquiring nosocomin pathogens, and cross-contamination between patients seems unlikely, even when multiple resistent organisms were initially present. the recommandation from some manufacturers to undergo extensive sterilization of fluidized beds after use does not seem warranted, at least with the bed used in this study. ant. koutsoukou, a, tahmitzi, p. kithreotis, m. koutonlidou, k. stavrakaki, kainis e, g. vlahogiorgos and e. eliopoulos icu-centre for respiratory failure -chest diseases hospital of athens. the cost-effectiveness issue is becoming vital in modern medicine and may lead to moral dilemmas since sometimes certain groups of patients may not have access to highly specialised modalifies. objective: our study compared the mean daily cost for antimicrobial medication in copd patients treated in icu versus all other patients in the context of relevant epidemiological, prognostic and outcome data. methods: age, sex apache ii score, length of icu stay (los) and in -icu fatality were retrieved from the files of all icu admissions over . mean daily cost for antimicrobial therapy per patient (dcat) was estimated. these variables were statistically compared between copd and non-copd patients. significance was assumed at p< . results: of the total admissions were fully evaluable. of them ( %) were copd patients. data (m---sd) results for statistical test are given in table i . copd patients were significantly older spent more time in the icu and presented with significantly higher apache ii scores. outcome and dcat were comparable in the two groups. objectives: the use of heat and moisture exchangers (hmes) during long term mechanical ventilation (mv) is increasing. in icu patients, they are routinely changed every day, according to the recommendations of the manufacturers, but the clinical basis for such a daily practice is lacking. we therefore prospectively assessed whether changing hmes (dar hygrobac, spa, mirandola, italy) every h only would affect their clinical and bacteriological efficiency. methods: two consecutive groups of patients requiring mv for > h were compared: group = hme replaced every day, n= episodes of mv in patients; group = hme changed every h, n= episodes in patients. tubings were not changed in the same patient during the whole length of ventilatory support. diagnosis of nosocomial pneumonia (np) was based on a positive quantitative culture (~ cfu/ml) of a protected specimen brush in patients with clinical signs of pneumonia. quantitative cultures of pharynx, trachea and y-cannector were performed every h. results: the groups were similar in terms of age, indication for and overall duration of mv ( +_ . vs +_ days, p= . ), and severity of illness (saps: --- . vs . +_ . , p= . ). the maximal values for peak airway pressure were identical in both groups ( . -+ . vs . • cmh , p= . ). obstruction of the tracheal tube was observed in only one instance in a group patient who had tracheal bleeding. circuit colonization was very rare, and of low grade in both groups. the level of patient colonization and the type of organisms were identical in both groups. more importantly, the incidence of np was the same ( / vs / , p= . ), as was duration of mv before the occurence of pneumonia ( • vs . +_ . , p= . ) and overall mortality rate ( vs , p= . ). conclusions: the clinical efficiency of this hme does not seem altered after days of use. indeed, replacing this hme every h only neither affect circuit and patient bacterial colonization nor the incidence of np. therefore, substantial savings could be obtained changing hmes every other day only. obiectives: to evaluate the usefulness of different paraclinical investigations for the diagnosis and prognosis of acute viral encephalitis in icu patients. methods: we reviewed patients (pts) admitted to our icu from july to december with the diagnosis of acute viral encephalitis. all were in coma and were initially treated as presumed herpes simplex virus (hsv) encephalitis. the causative agents were: hsv ( cases), herpes zoster varicellae ( ), measle ( ), rabies ( ), unidentified ( ). eleven pts survived and three presented neurologic sequelae. twelve pts were investigated by mri, and eleven also by spect and multi-modality eps. including brainstem auditory eps (baeps). these investigations were obtained as soon as possible following admission and were repeated during icu stay when possible. the clinical outcome was noted. results: six pts ( / ) had an abnormal mri. among them, pts made a complete recovery, in comparison with / pts with a normal mri. in one hsv infected patient, mri remained normal despite clinical deterioration and bad outcome. when repeated, mri became abnormal in cases (with poor outcome in one) and was improved in one. spect was found abnormal in / pts (among them, pts had thus a normal mr/). the correlation regarding the topography of brain lesions was poor between mri and spect. the findings of spect could not be correlated with a poor outcome. the baeps confmned in % of the pts the clinical diagnosis of brainstem involvement. changes in visual and somatosensory eps were mild in all the pts and were not helpful for the prognosis. eps were otherwise interesting for the follow-up of the coma in these sedated and ventilated pts. conclusions: the value of mri and eps for the diagnosis of acute viral encephalitis is of limited interest. spect seems to show early modifications, even in pts with a normal mri, but this test is poorly specific and does not correlate with mri changes when present. concerning the prognosis, larger studies should probably confmn that a normal mri could usually result in a good outcome. this serie illustrates also that hsv encephalitis could be demonstrated only in a small number of cases and that the prognosis of non hsv encephalitis is not easily assessed. objectives: to study the influence of gram (-) bacterial lung infections on liver function i~ mv icu pts. pts and methods: we studied pts, # ( , %), ( , %). hean age: , • years ( - ). mean stay in icu: , • days ( - ). they were divided in groups: a( pts) who did not suffer from pneumonia and b ( pts) who developed a gram(-) bacterial pneumonia. both groups were consisted of pts with same age, sex and disease distribution and same systemic failures. we measured sgot, sgpt, total bilirubin(tb), direct bilirubin (db), alk.phosphatase (al.ph.), v-gt and albumin (alb.) times: on days o, and of the pneumonia for group b and respectively for g~oup a. conclusions: ) in elderly intubated pts of an icu, kp is isolated more frequently than in icu pts< years (p<o, ). ) the frequency of isolation of kp in icu pts during - was - %, but now ( - ) kp becomes more and more rare ( - %) and is isolated especially in elderly pts. ) its sensibility to antibiotics remains always the same. ) the prognosis of np in our study was independent from age (p<o, ), sex, presence of bacteremia (p< , ) and type of invading microorganism. gram neg bacteria and renal failure (rf) from aminoglycoside toxicity are common and serious complications in critically ill patients. the aim of this prospective, pilot study was to compare the safety and adequancy of the endotrecheal (et) vs the intravenous (iv) administration of aminoglycosides. were measured in the plasma and the bronchial secretions at and hours after the iv (bolus) or the et (nebulized) administration of mg of gm in seven criticcally ill patients ( with established renal failure). safety was defined as peak and trough plasma gm levels _< than and ijg/ml respectively and adequancy as gm levels in bronchial secretions _> , ijg/ml. results: gentamicin was administered by the et and iv routes in and separate sessions respectively. a total of samples were assayed, in bronchial secretions (bs) and in serum. the et route resulted in higher gm levels in the bronchial secretions compared to the iv route ( , + , vs , _+ , pg/ml respectively, p = ns ). adequate bronchial gm levels were achieved in % of patients after et administration, compared to % after iv aaministretion. the blood levels of gm were significahtly lower after the et vs the iv route ( , + , vs , • , pg/ml respectively, p _< . ). the et administration resulted in toxic bronchia~ gm levels in % of the specimens. % of these samples were from patients with renal failure, however toxic blood levels were reached in only % of these. gentamicin seems to be a safe and adequate alternative route of treatment for the lrti. however, in patients with renal failure the et administration of the aminoglycosides should also be modified and continuously monitored. in order to evaluate the pathogenic role of anaerobes in nosocomial pneumonia (np), we investigated the systemic humoral response in patients who developed a np with anaerobic bacteria, especially prevotella species. methods: blood samples from groups of patients were tested. group i: patients with a np in which prevotella spp. was isolated from protected specimen brush (psb), group ih a control group of patients with a np without anaerobic bacteria, group ill: a control group of patients with dental stumps but without pulmonary infection, group iv: a control group of healthy voluntary people with prevotella spp. isolated from the dental plaque. an elisa was used to evaluate the total antibodies level against a mixture of four prevotella strains and a western-blot method was done to identify the antigenic proteins. results: data are expressed as means .+ sd. the antibody levels in patients of group i ( • was statistically higher (p=o.o ) than in the control groups (respectively: + , _+ , _+ ). using western-blot method, the intensity of the response was roughly superposable to levels obtained by elisa and the profiles were different according to the prevotella species. the occurence of a np with anaerobic bacteria (prevotella species) isolated from psb leads to an antibody response which seems specific of the prevotella species isolated. fever is common in the intensive care unit, but is not always related to an infection. we sought to define the epidemiology of febrile patients in a general medical/surgical icu. methods: we prospectively analysed the source of fever (t > . ~ c) in all adult patients admitted for >- hours in the icu during a two month period. these patients were studied for consecutive days. and werc classified in groups according to the evidence of infection (center for disease control criteria) after complete evaluation: documented infection: cdc criteria + isolation of pathogen (d); possible infectron: cdc criteria without isolation of pathogen (p); unlikely infection: patients who did nol meet the cdc criteria (u). results: of a total of patients studied, dec'eloped fever ( %). including (after complete evaluation) d, p and u palients. both the highest temperature in tile first day of fever and the maximal temperature were higher in d than in u ( . • versus . • and . -~ . ~ versus . - . , respectively p= . and p= . ). most common sources of infection in d were the lungs in patients ( %) and urina .ry tract in ( %). of these patients had positive blood cultures ( %). the overall mortality was % ( % in d, % in p and % in u. differences ns). antibiotics were given in % of d, % of p and % of u ( patients). in p there was a non significant lower mortality." in patients who received antibiotics ( / ( %) versus / ( %) patients, respectively). conclusions: in febrile icu patients both the highest first day" temperaturc and maximal temperature are significantly higher in infected than in non infected patients, but the differences are too small to be useful clinicall). mortality rate is not significantly influenced either by the presence of an infection or by the administration of antibiotics, obiective: retrospective study to determine the influence of candida infection on icu outcome. methods: patieet with a stay of more than days in inteaasive care were screened for candida infection. patients were treated with antifungal therapy due to either an increased antigen titre of -> : or clinical evidence of candida colonization. serological candida-antigens (ramco, pastorex) and antibody titres (hemagglutination, lgg-, igm-elisa) were examined routinely. seroconversion was defined as a threefold increase of antibody titre or a titre of : or higher. results: the median length of stay was (ranging from to ) days, the mean apache ii score on admission was (+_ . sd) points. of patients patients died ( . %). in the group treated with antifungnls ( patients) patients died ( . %). although of the patients only ( . %) developed a candida infection as defined above the mortality in the group that showed signs of infection was significantly higher ( . % vs. . %, p < . [chi-square-test]). in patients an antigen concentration-> : was measured. seroconversion was found in patients. the most common fungus was candida albicans ( . %). furtberm re, candida glabrata was found in . %. most of the patients were treated with x mg fluconazole ( patients). in patients therapy was changed to amphotericin b/flucytosine. in patients therapy was started with amphotericine b and flucytosine. in patients a threefold decrease of candida antigen titre was found. patients showed a decrease of candida antibody titre. conclusions: meticulous screening for eandida infection seems to be necessary since the number of patients with fatal outcome is significantly higher in the group with signs of fungal infections and thus requires immediate antifungal treatment. objective: early diagnosis of patients with ventilator-associated pneumonia (vap), and subsequent identification of causative microorganism, and selection of the appropriate therapy are critical important points that affect morbidity and mortality. the results of the quantitative bacterial cultures are not available for at least hours, while a two hours period, since the specimen are obtained is enough to know the gram stain results. the aim of this study is to determine the usefulness of gram stain in specimens obtained by bronchoaiveelar lavage (bal), through the bronchoscope. material and methods: we studied patients ( males and females, age + ) with suspected ventilator-associated pneumonia. the bal gram stain was considered positive when the specimen after a centrifugation at rpm for min revealed: i) more than leukocytes per optic field, ii) squamous epithelial cell less than percent and iii) one or more microorganisms per optic field on magnification. all patients had been receiving antibiotics, with no change during the last days, prior to bronchoscopy. results: patients had vap and patients did not. in cases the bal specimens (quantitative bacterial cultures) established the diagnosis of vap in the remaining three patients the vap diagnosis was established by other procedures (blood or pleural fluid culture, clinical outcome, autopsy). apache fl score in patients with vap was , -+ , , while in patients without vap was , + , . there was a significantly higher incidence of vap in patients who had i) coma (gcs < ) and ii) been receiving neuromuscular blockade (p< . ) . the sensitivity of the gram stain for vap diagnosis was %, the specificity , %, the positive predictive value %, and the negative predictive value , %. conclusion: our data indicate that the gram stain of bal specimens is useful for the early diagnosis of vap and the subsequent administration of the appropriate treatment. the role of anaerobes in mechanically ventilated patients with pneumonia (mvp) have been poorly investigated aim of the study : analyse the prevalence of anaerobic isolation in mvp. methods : between october and february all suspected mvp were investigated using protected specimen brush (psb) technique. brushes were rapidly transported in shaedler broth to laboratory. a special care was tooken for anaerobic isolation. results : among the psb performed for suspected mvp ( nosocomial and community-acquired pneumonia), yielded at least one micro-organism (positive psb : %). of positive psb demonstrated only aerobic bacteria and ( %) yielded with anaerobes. in out patients, anaerobes were associated with aerobic bacteria. anaerobes were mostly isolated in nosocomial pneumonia ( / positive psb). strains of anaerobes were isolated. prevotella species represent out these strains ( %) the most frequent anaerobic species were prevotella oralis ( ) p. intermedia ( ) and p. buccae ( ). comments:using adequate methods, anaerobic bacteria are frequently isolated in mvp. it could be off importance to take in account anaerobes in the choice of empirical antibiotic therapy in mvp. objectives: the majority of patients with multiple trauma are considered immunocompromised. the aim of this study was to identify risk factors of pneumonia in mechanically ventilated patients with multiple trauma or after surgery. methods: in this prospective study we studied multi-trauma patients (mean age + years, apache ii . + ), admitted to a general intensive care unit (icu). all patients were intubated and mechanically ventilated. we were considered that a patient had ventilator associated pneumonia (vap) when the specimens of bronchoalveolar lavage (bal) or protected specimen brush (psi?,), ebb'ned through the bronchoscope, had one or more microorganisms in concentrations greater than and cfu/ml respectively. all patients had been receiving antibiotics, with no change during the last days, prior to bronchoscopy. results: patients had vap, and patients didn't. in the bivariate analysis, the glasgow coma scale (gcs)< (x = . , p< . ), the administration of neuromuscular blockade (x = . , p< . ), the duration of mechanical ventilation to be greater than days (x = . , p< . ), the flail chest (x = . , p< . ), the parenteral nutrition (x = . , p< . ), the ards (x = . , p< . ), the abbreviated injury scale (ais) of more than for thorax (:,: = . , p< . ), the pneumothorax (x = . , p< . ) were statistically significant related to development of vap. in multivariate regression analysis, using the stepwise technique, three of the seventeen studied factors showed to have an indepantent association with the development of vap:the administration of neuromuscular blockade (f: . , p< . ), flail chest (f: . , p= . ), and gcs (< ) (f: . , p= . ). conclusions: in patients admitted to icu for multiple trauma or major surgery, the administration of neuromuscular blockade, the flail chest, and the gcs (< ), in the population under study, were the indepedent risk factors for vap. mof is a sereous complication of differem states: infection, sterile inflamation, extensive fissure injure, intoxication, ets. there is close correlation between extension of mof and death, developement of nasocomial infection. immunologic disfunction. in order to prgnose probability of risk of mof development among the patients with sepsis and septic shock, we achived an eqation, allowing to recive a coeficient, closely connected with this probabiliti. we have used retrospective analisis of cases of sepsis. diagnosis of sepsis was based according to bone's criterions of sepsis. mof was assessed as disfunction of or more systems according to bone's classification of mof. having used correlation analisis we have estimated factors which have had high correlation coeficient with the probability of development of mof. there were: apache-ii score points, evidenceof septic shock, endocrinopathy. with the help of multyple regression analisis we acheved next equation: y= , + , x~ + , x + , x , were x i-apache-ii score points, x -evidence of septic shock, x -endocrinopathy. the explanatory power of this quation was evidenced by roc of . , se (v - . introduction: the presence of liver dysfunction in the process of multiple organ failure is associated with an adverse outcome, particularly when it becomes progressive to liver failure. disturbances of liver function may occur early and their detection may be of significant importance for the further development of organ failure. routinely used liver function tests appear to be inconsistent indicators of hepatic damage. in this study, we used p_lasma disappearance rate (pdr) of indocyanin-green dye (icg) as an early estimate of liver function. methods: we serially evaluated pdr and routine liver function tests (serum bilirubin, sgot, sgpt), as well as acute phase and non-acute phase proteins (crp, transferrin) in patients during the first week after trauma or the onset of sepsis. patients: group : (n = ) multiple trauma iss > , group : (n = ): abdominal sepsis, acute necrotizing pancreatitis (anp) grade iii. patients were selected on the basis of clin cal estimates that these patients would require continued icu observation. pdr was determined by means of a fiberoptic catheter and a computerized system (cold z- , pulsion), which permits repeated bedside measurements. the initial values of pdr, serum bilirubin and transaminases were not significantly different in trauma, sepsis and anp. in trauma patients pdr improved during the first week. in patients with sepsis and anp pdr remained low and worsened with time. the decrease in pdr preceeded an increase in biochemical liver function tests in these patients. + . &-_ ( - ) discussion: routinely available blood tests of liver function are usually altered several days after injury. however, they are generally non-specific indicators and they are influenced by extrahepatic factors. pdr seems to be useful to evaluate impaired liver function early after the onset of sepsis and trauma. objectives: to study frequency of organ system failure (osf) and it's influence on outcome in granulocytopenic patients with hematological malignancies and septic shock(ss). materials and method: retrospective review of medical records of granulocytopenie(wbc< , xl ) patients with hematological malignancies and ss, who were admitted to the intensive care unit (icu). frequency of osf before and after ss was analysed. the patisnts were categorised on survival and non-survival. results: signs of osf were observed in . % of patients before ss and in all patients after ss. only patients presented with hypotension refractory to inotropic therapy. nevertheless there was a significant increase of frequency of acute respiratory failure (arf), acute renal failure (arenf) and liver injury (li) after ss occurred(showed on the figure). only frequency of organ failure before and after objectives: statusmetria allows to define the effective level of oxygen status and accordance to it means of carbon dioxide and elec-trolyte in critical care. the conception of syndrome int~ive care (sic) is exhausted itself and invariable outcomes of sic of multiergan system failure (mosf) confirms that. therefore, an alternative to sic should be advanced. methods: efficlenoy of treatment has been asscsaed in patients with mosf using value of metabolic rate and ability of an organism to cover it by oxygen and substrate supply. oxygen pulse (op) and index of efficacy of oxygen transport (ieto ) was monitored. ~lt~.lntenaive care is considered to be homeostasis-securing therapy (hst) if energostructure deficit is eliminated and necessary for recovery regeneration rate is .restored. op in patients with mosf was . mt-m " , and le,~ and ie'i~ w~ . units in sic. we managed to maintain op of . - . ml.m " and ieto of . - . units in hst. patients from with mosf survived in sic and patients from survived in hst. efficiency of hst appeared to be two times as much as efficiency of sic. cr of homeostasia-se-'uring therapy is advancing. the conception provides restoration of regeneration rate due to effective then in sic elimination of en=gostructure deficit. the conception may be a basis of new technology for treatment of mosf. helen f goode phd, nigel r webster phd. anaesthesia & intensive care, university of aberdeen, ab zd, uk. objectives: xanthine dehydmgenase is converted under conditions of ischemia, reperfusion and endothelial damage to xanthine oxidase, with superoxide anion as a co-product of its catalytic activity. multiorgan dysfunction syndrome is associated with splanchnic vasoconstriction resulting in significant and prolonged gut ischaemia. aggressive volume resuscitation with prompt restoration of blood flow results in reperfusion of the tissue and is likely to cause xanthine oxidase-mediated release of oxygen-derived radicals. this study investigates xanthine oxidase activation and oxygen-derived free radical-mediated damage in such patients. methods: fourteen consecutive patients on itu who met established criteria for septic shock and secondary organ dysfunction were studied. serum xanthine oxidase activity was measured using oxidation of a chromagen in a dual enzyme system and plasma malondialdehyde was measured using a specific spectrephctometdc assay. apache ii scores, blood pressure, svr, cardiac output and day survival were also recorded. biochemical data were compared with results from healthy subjects. results: xanthine oxidase activity was . + . units/i in patients (mean :t: sem) and . + . units/i in controls (p<o. , mann whitney u test), and was highest in the patients who survived (p< . ). malondialdehyde concentrations were elevated ( . • . prnol/i compared with . • . pmol/i in controls, p< . ). xanthine oxidase activity did not relate to apache score or any of the cardiovascular parameters recorded, and was not influenced by the degree of organ dysfunction. conclusions: patients with sepsis and secondary organ dysfunction have xanthine oxidase activation and evidence of free radical damage. the finding that activity was highest in those patients who survived suggests that reperfusion was incomplete in patients who died, with decreased tissue xanthine oxidase ~tash out' into the circulation. influence objective : evaluation of the feasibility of measuring the intragastrie partial pr~sure of carbon dioxide (pco ) using a chemilumin~nt optode and fibre~ptics originally developed for intrav~cular blood gas monitorlng(p ) methods the pco electrode w~ calibrated i~-vitro according to the m~ufaeturers instructions the sensor w~ then stripped of its outer c~ing and threaded down the pile tube of a g~ c enema e (gt) so ha he ens ng portion sat well within the balloon. the modified gt was inserted n~og~trically after induction of anesthesia in ten patients undergoing c~diopuimonary byp~s throughout results: according to the datas of integral rheography % of patients were revealed to have hypodynamic type of blood circulation (cardiac output was decreased on - % and general peripheral resistance increased on - %). it was effective to use complamin (xantinoli nicotinas) in the complex therapy of su~h patients. the dosage was - mg/kg during - days. as a result of such therapy was also the oliguric stage shortening (ac n ).in , % of the cases unsatisfactory datas of central hemodynamic,combined with high (more than cm h ) venous pressure,lung oedema.then nanipruss ( , - , mkg/kg/min) was succesfutly used in complex with routine therapy.in the patients with low cardiac output and low general peripheral resistance mesaton ( , - , mg/kg) and dopamine ( - mkg/kg/min) were effective.change for the worse in the hemodynamics datas, inspire of therapy during - days,was prognostically unfavourable. conclusions:we consider early diagnostic of hemodynamic disorders and adequate correction of them is one of the most important factors, determined the outcome and prognosis in arf patients. obiective: to evaluate the results of renal replacement therapy (rrt) in surgical icu patients with acute renal failure (arf). arf in icu patients is associated with high mortality rates. we investigated the relation between mortality and organ failure in different categories of surgical icu patients receiving renal replacement therapy (rrt) for arf. methods: the records of surgical icu patients with arf requiring rri-(haemodialysis or cavhd) were examined. five different patient categories were defined; .ruptured aneurysm of the abdominal aorta (raaa) n = .elective vascular surgery (evs) n = .abdominal sepsis n - .trauma n = .others ( e.g. malignancy, obstetric emergencies) n- seven organ systems (cns,circulatory,respiratory,hepatic,renal,digestive,haematologic) were scored for possible failure using the mof score. results: mortality was as follows: all patients % , group % , group % , group % , group % , group % . mortality increased with the number of failing organ systems; mortality for all patients with > failing organsysterns was % the only exception being the subgroup of trauma patients where mortality under these circumstances was o% conclusions: mortality in surgical icu patients receiving rrt for arf is high. no significant difference in mortality is found between raaa and evs. mortality increases with the number of failing organ systems. the subgroup trauma patients shows a lower mortality compared to the group as a whole, even with > failing organ systems. to look for the most accurate scoring system to measure the severity of the complications occuring in the early phase ( first day) of kidney transplantation and to asses their prognostic value. methods: in our retrospective study we applied the apache li and the goris scoring system for the kidney recipients who developed multiple organ failure (mof) as a consequence of their pulmonary and. cardiovascular complications following kidney transplantation. we evaluated the recipients the distribution of the women and men ( % ~ % ) was the same as in the kidney recipients. applying the apache ii system most of the patients had their score between and , and the function of , or organs were affected at the time of the onset of mof. the apache ii system gave adequeate information about the disturbance of the function of other organs beside the kidney failure even at the time of the transplantation. the scores and the number of the affected organs correlated with the condition of the patients in the goris scoring system but not as sensitively as in the apache ii scoring system. conclusions: both the goris and the apache ii scoring system can be applied to measure the severity of the multiple organ failure occuring during the early phase of kidney transplantation. however the apache ii system is more suitable to follow not only the stateof the patients at the time of the admission but also the changes occuring in their condition during the complication. v.v.erofeev, v.v.ivleva scientific research institute for general reanimatulogy russian amsci, moscow, russia objectives: the analysis of ssc and results of their treatment in patients following critical states showed the necessity of developing a combined antibacterial therapy. methods: according to the protocol patients ( - years old) with combined trauma and massive hemorrhagy following vast aml traumatic operations were examined. microflora's composition and resistence to up-to-date antibiotics was studied using the anaiyser iems reader by "labsisteme"(finland). general clinical, bacteriological, immunological indices, as weil as the duration of the treatment and recovering rate served as criteria of the combined antibacterial therapy effectiveness. results: it was proved expedient to administer antibiotics in staphylococcus infection in the following combinations: riphampizin with fluoroquinolones; i-ii degeneration, cephalosporins with aminoglycosides; cephalosporins with fluoroquinolones. in case of singling out the exciters of the euterobacteriaceae family, including the pseudomonas aereginosa, -fluoroquinolones combined with modern amynoglycosides; fluuroquinolones with ureidopenicillines; ureidopenicillines with amynoglycosides; amynoglycosides with the ii-iii generation cephalosporins; cephalosporins with fluoroquinolones. in severe ssc caused by combined infection (including anaerobes) clindamicin with modern amynoglycosides was prescribed. conclusion: the combined antibacterial therapy allows: ) to increase the effect on microbic agents and the efficacy of treatment in combined infections; ) to lessen the possibility of the exciters'resistence to antibiotics; ) to prevent the development of superinfection: ) to decrease the doses of medicine and its toxic effect. objectives: two methods of blood volume measurement in a group of critically ill patients were compared to investigate the practical possibilities of a new easy to use method based on carbon monoxide (co) uptake. methods: all patients had multi-organ failure and haemodynamic monitoring with a swan-ganz catheter. mean apache ii score was ( - ). when indicated, patients had blood volume measurements simultaneously based on the techniques of, i) dilution of ~cr labelled red cells, and ii) inhalation of carbon monoxide gas with measurement of the rise of carboxyhaemoglobin produced. the co was administered via a newly designed, ventilator driven, fully closed circle system ensuring co retention and co removal with automatic addition of oxygen to m}ttch patient uptake. a portable computer performed all necessary calculations. results: volumes obtained by co uptake were compared with the "gold standard" radiolabelling method. mean blood volume determined by the co method was ml ( - ml) compared with ml( - ml) with slcr labelled red cells (r= . ). regression analysis produced an intercept at ml. the slope of the regression line was . ( . - . , % confidence limits). discussion: the co method produces volumes in excess of the radiolabelling method. there appears to be a systematic error, and one possible explanation is co binding to substances other than haemoglobin. conclusion: the co method is easier to use than radiolabelling and of the lower cost, since cohb measurement only is required. aceuraey is sufficient for clinical use and our preliminary findings suggest this system will meet the requirements. objectives: this study was conducted to determine the role of nitric oxide (no) in the pathophysiologic alterations and multiple organ damage, and the possible effects of " " " (l-n -monomethyl-l-arglnlne nmma) on hemodynamics and mortality in rats caused by a prolonged hypovolemic insult. methods: a prolonged hemorrhagic shock ( - mmhg for rain) was induced in anesthetized rats followed by adequate resuscitation. l-nmma was administered intravenously at doses of . mg/kg or . mg/kg at the end of resuscitation. results: infusion of . mg/kg l-nmma diminished the fall in mean arterial pressure, significantly increased the cardiac index (ci) and stroke volume (sv), together with remarkable protection from multiple organ damage compared to the controls. the h survival rate was significantly improved from . % in the control group to . % in the treatment group (p< . ). in contrast, the high dose of . mg/kg l-nmma resulted in a strong blood pressure response but a marked reduction in ci and sv concomitant with an increased total peripheral resistance index within the observation period, and caused severe damage to various organs at h after treatment. in addition, marked elevation in both endotoxin and tnf levels were observed in animals subjected to shock insult. conclusions: these results suggest that no induced by hemorrhagic shock in rats is an important mediator for pathophysiologic alterations associating with cardiovascular abnormalities, multiple organ dysfunction, and even lethality. thus, regulation of no generation and use of no inhibitors might provide new aspects in the treatment of hemorrhage related disorders, and the use of l-nmma would be either deleterious or salutary in a dose dependent manner. (hebert, chest- ) . the purpose of this study was to assess the risk factors for hepatic dysfunction in mosf. methods: patients have been hospitalized in our icu from january to may . , ( %) with mosf. among mosf pati~ts, ( %) have had hepatic dysfunction defined according to hebert (bilirubin ~ ttmop , chest ). thirty six of these patients acquired hepatic dysfunction after admission in the icu. these patients were compared with mosf patients without hepatic dysfunction selected blindly. chrorfic diseases, severity scores, eanse of admission, clinico-biologieal and hemodyunrrfic parameters, use of vesopressors, use of hepaiotoxic drugs, use of nutritional support and mortality were compared for hepatic failare and non hepatic failure groups.twenty nine patients had postmortem hepatic histologic examination, results: univaciate analysis: only parameters with p _< . are pre~nted. including these paramet~'rs in a multivariate analysis, anly c~hosis and vascular surgery remain independent risk factors for hepatic dysfunction. in particular, pao /fio , arterial lactate, do were not different between the two groups, some de~'ee of histological abnormalities was found in all liver samples, despite a normal bilirubin level in % of the cases conclusions: in our patients, conu'ary to previous studies, hypoxic and hemody~anfic parameters were not independent risk factors for hepatic dysfantion. this might be due to the inadequacy of the usual biologic definition of hepatic dysfunction as well as to the poor sensitivity of general hamodynamic parameters. critical states of various origin are complicated with the mldtiorgan farm (moi~ oceuzr~ce. due to their and functional features the lungs become the primmy damage target in various critical.states. ard that occurs in such states is associated with pulmonary edema development because of capillary permeability increase mediated by humeral and cenular responses to amag/~ factors exposure. r nmst be emphasized that mediators and effecto~rs of this respo~e affect not only puknonary capillaries, but other organs capiu~es as wellenhancing their permeability. orsans edema is a conmm~ finding at the autopsy of patients died from mof.clinical and radiolosial findings allow to have a diagnosis of pulmonmy edema before ~mi!ar lesions in other organs occm. additionally, there are some techniques that permit quantitative assessment of pulmonary edema flv.id (evlw) volume. in conclusion, we suggest that evlw changes in .dyn~rmcs in patients with mof are considered as a critical state severity measure which reflects indirectly the edema in other organs. objectives: we compared three different dialysis membranes to find out whether or not there were differences between their clearance characteristics on substances such as inuline, creatinine, urea, and phosphate to be eliminated in acute renal failure (arf). moreover, if a loss of clearance did occur we were interested in whether this was due to heparinization and a high production of the thrombine-anti-thrombine-complex (tat). methods: we carried out a randomized controlled study on consecutive critically ill patients presenting with arf, most of them in association with multi-organ failure, to be treated by continuous pump-driven arterio-venous renal replacement therapy on continuous low-dose heparinization. three different types of high-flux filter membranes (f tm [fresenius] , ct tm [baxter] , and filtra tm [hospal]) were assessed. each filter was changed intentionally after a hours" use. together the data of filters were evaluated, each at three different times (immediately after its onset [ hi, after h, and after h). the clearances of creatinine, urea, phosphate, and inuline were measured. results: there were some significant differences in clearance characteristics of inuline, creatinine, urea and phosphate between the filters (p< , ) showing the f tm membrane excelling filtra mand ct tm the more. the loss of inuline clearance ( mi/min/m ) after h, however, was insignificant for all filter types. a continuous low-dose heparinization scheme was applied without any relevant prolongation of the aptt. even lower losses were noted for the clearances of creatinine, urea, and phosphate. we found the tat-producfion increased after h (p< , ), but it did not rise any further. conclusions: as we could demonstrate in our study the clearance data of different types of filter membranes applied during continuous renal replacement therapy do show significant differences. on the other side, no relevant loss of clearance occurs during a hours" period indicating a high efficiency over time. to consider commercial aspects as well it shows that inexpensive conventional filter membranes can successfully be applied even for a longer renal replacement period, if needed. a retrospective study was performed on patients with acute renal failure (arf). we analysed survival in continuous (cd) and intermittent dialysis (hi)). mean age of the patients was years (y), patients ( % ) were < y, patients ( %) were >= y. the incidence of dialysed arf in our mixed intensive care departement is %/admission/y. statistics: fischer's exact test, mann-whitney-u test. efioloev: the contribution sepsis, cardiac failure and aminnglycosidcs was respectively %, % and %. treatment: cavh (cd) or cvvh (cd) was used in patients ( %), hemedialysis (hd) was used in patients ( %). data: mean apache scores were the same for cd and hd ( for both groups), patients treated with continuous dialysis techniques had significantly (p<o, ) more need for ventilation ( % vs %), elevated bilirubin ( % vs %) and a higher vasopresser need ( % vs %@ than patients treated with hemedialysis. there was a trend towards more sepsis ( % vs %; p= . ) mad coaguiation disorders ( % vs %; p= . ) in cd. taere were sign/ficantly more younger patients (< y) treated with cd ( % vs %, p< .os). mean apache score was significantly lower in patiants< y than as patienta>= y ( vs ; p< . ). patients< y had significantly (i}< . ) more coagulation disorders ( % vs %) and elevated bilirabin ( % vs %). there was no significant difference in vasopressur need and ventihatio~ between age groups. outcome:. hi) had a better sr compared to cd ( % vs ~ p< . ). patiants>= y had a comparable sr vs patients< y ( ") */e vs %; p----a.s.). tha global survival rate (sr) was % ( patients). conclusions : diaiysed arf has a well known lowsurvival rate ( %): hc~raedialysed patients had a better survival rate than patients treated with continuous dialysis. this can be explained by the fact that the latter were in a worse condition considering organ failure (more vantilatian, elevated bflirubin and need for vasepressurs), apache score couldn't illustrate that. patient~ y with arf have the same survival rate as patients< y: although patients >=- y have a higher apache score they have less organ faille. the avacbe score is not a good oredictor of survival in p with organ failure. departments of surgery and intensive care, guy's hospital, london, u.g-obiectives: a randomised controlled trial of a management protocol utilising the regular measurement of gastric intramucosal ph (phim) to control the administration of dopexamine. methods: patients admitted to a multidisciplinary teaching hospital intensive care unit (icu) undergoing insertion of a pulmonary artery catheter were managed according to a resuscitation protocol. randomisation was to either the protocol alone or to insertion of a nasogastric tonometer and subsequent management guided by phim. phim < . initiated volume and inotrope resuscitation and, if unsuccessful in elevating phim, dopexamine was commenced. approval was obtained from the hospital ethics committee. results: patients were considered for analysis and the two groups were well matched for age and sex. overall, there was a high hospital mortality of . %. there was no difference in icu or hospital mortality between the two groups (see table) . objectives: to compare cardiac output (co) measurements between continuous termodilution (cco) by thermal wire on pulmonary artery catheter (cco/svo vigilance. baxter critical care), and co measurement using a trans-esophageal doppler (dco) ultrasound system (odm ii, abbott laboratories), in the immediate postoperative period of cardiac surgery. methods: patients undergoing myocardial revascularization were monitored with cco by a swan-ganz catheter and an intra-esophageal dco probe, after induction of anesthesia. exclusion criteria were: aortic valve disfunction, previous valvular surgery esophageal disease, absense of sinus cardiac rhythm, and need of ventricular or intraaortic assistance. hemodynamic parameters, co by both cco and dco, svo . sao , diuresis, pha, and hemoglobin were repeatedly registered during the first hours after surgery, as the patients were kept under sedation and mechanical ventilation. results were compared using the method described by bland and altman. results: measurements of co were obtained, ranging . objectives: a decreased tissue oxygen delivery is responsible for a higher morbi-mortality rate among surgical patients; this diminished oxygen delivery/consumption rate (dojvo ) may origin the lactic acidosis observed in the gastrointestinal tract, reported in patients undergoing hypothermic cardiopulmonary extra corporeal surgery, and can be registered by tonometry as result of the gastric mucose ph. the purpose of this study is to evaluate the reliability of the intramucosal ph (phi) measurement by a nasogastric catheter as indicator of the do /vo > its co> relation to other parameters of do /vo disturbance, and with postoperative complications and clinical course. methods: patients ( male, female) undergoing cardiac surgical procedures were included ( myocardiai revascularizations, valvular substitutions, constrictive pericarditis). mean age was + years, mean weight _+ kg. a nasogastric probe (trie tonometrics) was placed after anesthesia induction; phi values were registered in the postoperative period ( ', ', ", ' and h after surgery end). the corresponding hemodynamic parameters, venous oxygen saturation (svo ), diuresis and arterial ph (pha) were also recorded. results: phi values ranged . to . (mean . ( . ); the mean values of clinical evolution were: extubation time, _+ hr.; discharge from postoperative care unit, - hr.; and hospital total postoperative time, _+ . days. complications registered were: perioperative acute myocardial infarctions, cases of respiratory insufficiency, occlusion of coronary bypass, an ease of hyperamilasemia. all patients with severe complications needing specific treatment showed either a low phi value, or a considerable descent in comparison with the initial register. statistic correlation between low phi and presence of complications was found; the low significance (p > . ) degree may be due to the low population size. conclusions: phi measurement in cardiac surgery patients is a non invasive, uncomplicated method for prediction of doz/vo disturbances, thus reflecting risk of increased major complications, and may precede changes in other usual indicators (svo , pha, cardiac output, ...). work-in-progress with a greater population size may offer more significant results. references: ( ) gutidrrez g: lancet ; : - . ( ) landow i: acta anaesthesiol scand ; : - . the haemoglobin-level (hb) is besides the arterial oxygen saturation and the cardiac index one of the relevant parameters of oxygen supply to the tissue. in contrast to otherwise healthy patients, there is no agreement on tile so-called transfusion-trigger in critically ill patients. in i?ont of this background the question arises, whether and to what extent blood transfusion in critically ill patients improves oxygen supply io tile tissue. this study was performed in critically ill/septic patients in the postoperative period alier an inlcclive/scptie revision operation of the hip or knee joint. on cardiac/seplic reasons monitoring consisted beside other measures of a pulmonary arlery catheter and of an indwelling arterial line li~r measurering/calculating standard haem~dynamic as well as systentic oxygen parameters. the indication for blood transfusion was given by hb together with the cliuical slatus of thc patienl (asa-scorc and multiple organ dysfunction (moi))). statistical analysis w~ks performed by mann-whitney-u-test. by fisher's exact-test and by wii.coxon-test: statistical significance was set with p< . . according tu the pretransfusion value of hb and of lactate (lac) palicnts ;,,'ere divided into groups as follows: a: hb< and b: >sg/dl: i: ac< . and ii: > .smm. in either group blood transfusion results in zt significant increase in hb (a: . _+ . to . + . g/dl; b: .(~ . tt, . + . g/dl; i: . -+ . to . -+ . jdl; i : . -+ . to . + . g/dl). wlailc, however, haemodynamic parameters do not difl)r significantly from each other before and alter blood transfusion, oxygen delivery (do, -ml/min x m-') increases significantly hi either group studied (a: -+ to -+ ; b: + to + ; : -+ to -+ ; i : -+ to -+ ), in contrast oxygen consumption (vo~ -ml/min x m e) does not change significantly in either group (a: i -+ to -+ ; b: -+ to -+ ; i: -+ tu -+ ; : -+ to +_ ); oxygen exlraction ratio decreases. this study in critically ill/septic patients demonstrates, that in this group of patients studied blood transfusion at a base-line-value of > . -+ . g/dl expectedly rises do~, however, it does not improve vo=; even not in septic patients with elevated lac-values. paclitaxel in a new anticancer agent, extract from the bark of the yew tree (taxus brevifolia), employed against breast and ovarian cancers resistant to chemotherapy. it promotes the polymerization of tubuline, and disrupts the normal microtubule dynamics. hematologic toxicity, hypersensitivity reactions (bronchospasm, urticaria and hypotension), and peripheral neuropathy are the main reported toxic effects. cardiac side effects are rare: atrioventricular blocks of higher degree are reported in . % of patients; congestive cardiotoxicity was discussed only in one trial in patients treated with paclitaxel and doxorubicin. we describe the history of a -years-old worn an with a breast cancer, diagnosed in , initial staging t nim , treated with mastectomy, axillary lymphadenectomy, andchemotherapy with a cumulative dose of anthracyclines of mg/m until august . the patient complained of dyspnea and severe hypotension immediately after an intravenous infusion of mg paclitaxel, given over hour for the treatment of bilateral, malignant pleural effusion. at echocardiography die left ventricular ejection fraction was reduced to %. she died days later because of a severe cardiac low output with hepatic and renal failure; an impressive hepatic cytolysis was observed. the post mortem examination confirmed the dilatation of the cardiac cavities, especially of the right ventricle, bilateral pleural fluid, and ascites. the histology was suggestive for a cardiomyopathy secondary to anthracyclines. the electron microscopy revealed a deposition of an unusual pathological pigment in the myocytes; subsarcolemmal deposition or membranous were absent. we hypothesize that paclitaxel was the cause of a major hypersensitivity reaction with shock and severe hepatic cytolysis, worsening the myocardial damage induced by anthracyclines. the possibility that a low doge of paclitaxel could directly increase anthracyclines cardiotoxicity -as decribed in the medical literature -will be discussed. objectives: activated endothelial cells release soluble intercellular adhesion molecule- (sicam- ), vascular cell adhesion molecule- (svcam- ), and e-selectin (selam- ). sicam- , svcam- , selam- , and inflammatory cytokines were determined. methods: sicam- , svcam- , and selam- were determined by elisa. tnf-a, il- , and il- were also measured by elisa. endotoxin was measured by an endotoxin-specific endospecy test after pretreatment of new pea method. results: the sicam- and s vcam-i levels were significantly higher in the septic multiple organ failure (mof) and sepsis groups than in the non-septic mof group. the selam- level was slightly higher in the septic mof group than in the sepsis withut mof group and non-septic mof group. the increases of soluble adhesion molecules were not in agreement with changes of plasma endotoxin level. levels of soluble adhesion molecules were correlated with the levels of plasma tnf-a and il- , but the level of il- . discussion and conclusion: the slcam- and svcam- levels in septic patients closely reflected the severity of the pathophysiological conditon. it was possible that the release of sluble adhesion molecules were not stimulated by plasma endotoxin, but endotoxin in the local infectious region. tnf-c~ and il- also were suggested to be involved in the release of these soluble adhesion molecules. obiectives: cardiopulmonary bypass (cpb) surgery is associated with a systemic inflammatory response attributable to the release of various inflammatory mediators and the activation of complement or coagulofibrinolytic system. in addition, adhesion molecules, such as icam- , elam- , and vcam- , appear to be of central importance in the inflammatory process following cpb surgery. we previously reported the effects of a synthetic protease inhibitor, fut- , reduced release of inflammatory cytokines (tnf, il-lg, il- ), activation of complement (c a, c a) or coagulofibrinolytic system (tat, pic, fpa) and protected platelet function (gpib, gpiib/llla) following cpb surgery. methods: in this study, we analyzed fut- on soluble adhesion molecules following cpb surgery. patients undergoing cpb surgery were divided into two groups, group a consisted of patients who received omg of fut- in priming solution, followed by a continuous infusion at mg/kg/hr during cpb in addition to initial heparin dose of mg/kg. group b, a control group, included patients who were injected with heparin only. the plasma slcam- , selam- , and svcam- concentration was measured by elisa. results: every soluble adhesion molecules decreased during cpb in both groups, and rose after cpb. selam- and slcam- reached their peaks on hours after cpb and on pod respectively in both groups, but they remained lower in group a (selam-i: . + . vs. . • ng/ml, p< . , slcam-i: • vs. • ng/ml, p< . ), svcam- , in both groups, remained lower than preoperative levels, but did much lower in group a. conclusions: fut- reduced adhesion molecules and suggested to be the effect on postoperative organ dysfunction. in the last few :,'ears the conditions of treatment in continuous hemofiltration/hemodiafiltration were discussed controversially. a significant removal of tnf-alpha and il-i could be demonstrated in cvvhd. the aim of our study was to investigate the elimination of tnf-alpha, l- , il- , il- , s-cd- and ifn-gamma in cvvh by measurement in plasma and hemofiltrate of critically ill patients with an acute renal failure. the patients of our study were treated with a continuous veno-venous-hemofiltration (polysulfone-filter, blood flow: - ml/h, filtration rate ml/h). the samples, hemofiltrate and plasma, were taken one hour after the start of treatment. the patients suffered from septic shock ( ), the so called hepatorenal s~aldrome ( ) and a severe pancreatitis ( ). the cytokine concentrations were measured with elisa-method. in contrast to elevated concentrations in plasma for tnf-alpha ( cases), scd ( cases), il- (l case) and il- ( cases), hemofiltrates contained no activities. only il- was removed in significant amounts with even higher levels in hemofiltrate than in plasma. this phenomenon was described so far for tnf-alpha and il- and may be due to the absence of metabolic properties (possibily enz~natic) in hemofiltrate. it can be shown, that tnfalpha, il- , il- could not be eliminated in cvvh with a filtration rate to ml/h. in contrast to findings of other investigators with a higher filtration rate (> ml/h), we found no significant concentrations of tnf-alpha and il in hemofiltrate. we conclude, that for a significant removal of important cytokines higher filtration rates (> ml/h) are necessary. objectives: multiple organ dysfunction syndrome including liver and renal impairment is a fatal complication in patients with the diagnosis of sever sepsis. this study focused to the effects of removing toxic substances from inflamnatory tissue by hemodiafiltration. ~ ethods: eleven patients were admitted to the icu in emergency center and met the criteria of systemic inflammatory response syndrome in association with infection. all patients developed liver and renal dysfunction and were treated by hemodiafiltration with high flux membranes (fb-u:nipro). the hemodiafiltration were performed times using nafamostat mesilate as an anticoagulant in hours with l of substitution fluid (hf-b:fuso). the serdm levels of endotoxin, cytokines, endothelin-i (et-]), human neutrophil elastase ~ -proteinase inhibitor complex (hne-pi), fibronectin (fn), lactate, and amino acids were measured before and after the hemodiafiltration. the hemodiafiltration would be effective to renal dysfunction by reducing endothelin and beneficial to tissue metabolism represented in fisher's ratio, but might be harmful to respiratory function by activating neutropila in patients of severe sepsss. background : intermittent hd may be poorly tolerated in the early phase of arf in hemodynamically unstable patients (pts). this technic may fail to achieve steady state urea low levels in hypercatabolic pts. method : nt = consecutive pts treated with hd; n = consecutive pts treated with cvvhf. hemodynamic unstability is defined by arterial hypotension and requirement of inotropie support despite adequate filling. rate of change in urea (u), ereatinin (cr), k + , ph were computed from a linear regression .analysis of data vs time in each treatment group during the first days of application of the two technics (anova). dally worst values were recorded. results : hd-group : apach% score = _+ ; mean number of organ system failure (osf) = . -+ ; mean blood pressure (mbp) = • mmhg (first day of application of hd). cvvhf-group : apachen score : + ; osf = -+ ; mbp = + mmhg (first day of application of cwhf discussion : during the first days of application of hd/cvvhf, u and cr decreased much more rapidly in the cwhf-group. k* and ph were maintained within normal range in the two groups. initial mbp which was much lower in the cwhf-group significantly improved during the application of cvvhf while mbp remained unchanged in the hd-group. conclusion : despite higher severity of disease in cvvhf group (apachen score, osf, lower initial mbp), we obtained a better performanco with cvvhf regarding the decrease of u and cr and the improvement of mbp. in relation to the different and continuous renal replacement techniques, the continuous venovenous one is the alternative method to continuous arteriovenous for critical patients with acute renal failure (arf). we present you our experience with cvvh in patients with mof. in our intensive care unit (icu) patients with mof were treated with cvvh in the period between january in to march in . the mean (• age of our patient population was , • years, being % male and % female the whole patient population was with mof iust at the moment the technique was accomplished; % was in mechanical ventilation, % needed vasopressor support and % required both of them (mechanical ventilation and vasopressor support) apache ii score mean of the patient population was , ~: , (range - ) and ati of them were with arf oligoanudc. technique: cvvh was accomplished using a single-d~al iumen catheter, ptaced in either a temoral or subclavian vein by the stand ard seld{nger technique. pol{sultone hemofitiers were also used, and the extracerporeal circuit used standard arterial-venous blcod tubing. blood flow and hence oltrafiltration pressure, within the circuit was generated by a roller blood pump. the modulus has a roller pump, a pressure transducer connected in an arterious and venous line, such as an air-transducer which is adapted to a drip-chamber in the return way. the replacement used was a peritoneal dialysis solution. medicine , st. george's hospital medical school, london. england. hepatic sinusoidal endothelium shows a major inflammatory response in porcine sepsis that can be attenuated by the administration of dopexamine hydrochloride. dopexamine is a beta and dopaminergic receptor agonist. the specific beta adrenoceptor antagonist ici has been shown to reduce the protective effects of dopexamine. we investigated the effect of this antagonist on hepatic ultrastructure in porcine sepsis. six pigs ( - kg) divided into groups were anaesthetised and intubated. cardiac output and portal blood flow were measured using standard techniques. the groups were; placebo, (peritonitis induced); blocker, (peritonitis induced and pg/kg ici bolus infused then given hourly). caecal content was aspirated and peritonitis induced. colloid was infused to maintain pawp at - mm hg for eight hours the animals culled, hepatic tissue removed and prepared for electron microscopy. in the placebo group hepatic endothelium was swollen and the sinusoids occluded by wbc. but in the ici blocker group, much of the sinusoidal endothelium was absent and there where large extra sinusoidal spaces among the hepatocytes. an assessment of the two groups showed worse hepatic architecture in the blocker group. the b antagonist blocked any protective effect of endogenous beta adrenoceptor agonist (adrenaline) on hepatic endothelium in porcine sepsis. george's hospital medical school, london. england. dopexamine hydr chloride, a beta and dopaminergic receptor agonist reduces hepatic damage in porcine sepsis. we tested dopexamine's effect on cerebral oedema. the beta adrenoceptor antagonist ici was infused to block any protective effect of dopexamine. nine anaesthetised pigs ( - kg) were randomised into groups; placebo, (peritonitis induced); dopexamine, (peritonitis induced and ~tg/kgdar of dopexamine infused); blocker, (as in dopexamine group but in addition pg/kg ici bolus given then infused at that rate hourly). caecal peritoneum was induced and colloid infused to maintain pawp at - mmhg for eight hours when the animals were culled, cerebral tissue removed, prepared for electron microscopy and digitisation. digitisation of the area of oedema surrounding the blood vessel and expressed as a percentage of the micrograph. . _+ . , dopexamine . + . ", blocker . + . . data expressed as mean + sd. significance p< . . * dopexamine compared to placebo and blocker. in the dopexamine group the area of tissue oedema was significantly lower than either the placebo or blocker groups. there were no significant differences between the placebo or blocker groups. the antagonist completely blocked the protective effect of the drug on cerebral oedema in porcine sepsis. beta adrenoceptor stimulation is protective of cerebral oedema in porcine sepsis. objectives: the hemodynamie~ of hepatic circulation during multiple organ failure (mof) have not been suffleienly studied. we investigated liver hemodynamics in two subgroups of patients with mof, those with either liver or lungs as the main organ of involvement. methods: three groups of patients were created: i) mof-hepatic involvement (mof-hi) ( patients) with bilirubin > . mg/dl and lung injury score < . , it) mof-ards ( patients) with respective values < . and > , iii) patients with head injury with respective values < and < , served as group control. all patients were in haemodynamieally stable state with an oxygen delivery index > ml/min/m prior to measurements. two swan-ganz catheters 'were inserted, one in the hepatic veins and one in pulmonary artery and the following measurements were determined: the hepatic vein free pressure (hvfp), the hepatic vein wedge pressure (hvwp), cvp, paop and co. the gradient of hvwp-hvfp represents liver perfusion pressures. by injecting contrast media at dose of iml/lokg with the balloon inflated to achieve sinusoidai image, the hepatic blood flow (hbf) was concluded by the time in seconds of media removal after balloon deflation. results: the co, cwp and cvp were comparable to all three groups. namely, for mof-hi, mof-ards and control groups the mean (+sd) value of co was . _+ . vs . _+ . (ns) and . _+ . respectively, of the paop was . +_ . vs +: (ns) and . + . respectively and of the cvp was .+. . vs . + . (ns) and . respectively. in contrast the two mof groups were different after the cut-offinclusion criteria ie the mean (+sd) value for bilirubin was . + . vs . + . ( < . ) and . _+ . respectively and lung injury score was . objectives: oxygen delivery (do ) and oxygen consumption (vo ) are increasingly monitored parameters in the icu. there still remain controversies about an oxygen supply dependency in critical illness particularly with respect to vo determination by either indirect calorimetry (vo m) or tick calculation (vo c). the purpose of this study was to investigate the changes in vo m and vo c following do increase. methods: the relatives of critically ill patients (mean age years, mean apache ii , mean mof-score ) gave their written informed consent to participate in this institutionally approved, prospective study. do was increased by fluid loading (hydroxyethylstarch %: mean volmne ml, mean duration of infusion min) and catecholamine support (dobutamine: mean dose , ~g/kg/min). changes in vo m and v c were recorded sinmltaneously before, during and following interventions. calorimetry was obtained with the metabolic monitor integrated in the ventilator (puritan bennett, carlsbad, ca adaptive endocrine response of organism to septic shock consisting in activation of the production of adrenal hormons, renin -angiotensin -aldosterone system (raas) and other hormonal systems has an influence over microvascular changes in these states and for development of multiple organ failure (mof). in patients with peritonitis of different origins ( nonsurvivors and survivors) were followed the changes in cortisol level and raas by radioimmunological methods and many variables for evaluation of respiratory, renal, hepatic function, coagulation etc. as a signs of mof. it was observed significant increase of the level of cortisol ( +_ , nmol/ i), aldosterone ( , • , nmol/i). by factorial statistical analysis we found significantly high correlations between hormonal changes and respiratory function (for example r=- , , p < , between cortisol and pao ; r = , , p < , between cortisol and d (a-v) ; olso renin -cao r=- , , p < , , renin d ~,vl o r = , , p < , ). such significant correlations was found and for raas with respiratory, renal function, byproducts of arachidonic acid thromboxan b and p fla, soluble fibrine degradation products etc. these correlations between the degree of endocrine changes and multiple organ failure in patients with septic shock produced by peritonitis suggest that their effects upon peripheral vascular resistance and constriction of the splanchnic, splenic, renal and other organ vasculatures are not always with physiologic expediency and there are perhaps the possibilities of therapeutic influence. intredu~on : dopexamlne has previously been shown to control hyperkalaemia ia patients with acdto renal failure (arf), however effects on the subsequent course of art are undomunente~ ob_iectlv~ : to evaluate clinical progress in patients with acute renal failure (arf) in an intensive care unit (icu) with regard to biochemical control, need for -and time to -dialysis, and outcome in patients receiving dopexamine. m~ods : consecutive patients meeting standard criteria for diagnosis of arf were included in the study. full cardiovas~dar, biechemical and intervention/outcome details were recorded. dopex.~min~ was infilsed at a dose of pg/kg/min in conjunction with a regimen of inotropir support and blood volume optimization. resn]~ : following the intzoduetion of dopc',~mine ilrinr vohlmes increased slightly over the next hrs fzom + ml/ hrs to + ml/ hrs (ns). data expres,uxl as mean + sem. three patients ( %) became polyuric with urine output > ml/hr within days and did not need dialysis. in the remaining patients the time to dialysis (to correct acid-base deficits or volume overload) was . + . days. serum potassium levels were well controlled. day or immediate pre-dialysis levels were . + . mmol/l compared with pre-lreatment . + . mmol/l overall mortality in this series was / ( %). duration of acute dialysis in survivors with renal recovery was . +_ . days. patients ( %) progressed into chronic renal failure and needed continuing renal replacement therapy. no adverse cardiovascular altects were seen at this low dopoxami~ dose although its competitive inhibition to adrenergic reuptake mechanisms meant that doses of pressor agents could often be reduced. : dopcx:~minr nsed in conjunction with inotropic support and blood volume oplimitntion, can safely postpone, or even avoid, the necessity for acute haemodialysis in icu patients. no evidence of tachyphylaxis to the effect on serum potassium levels was seen over the duration of the study. hen'era m., suarez g., dagn d., varela a., ramos j., garoia jm, aragdm c, jurado l, medina a. icu. hospital regional. malaga. spain. objective: to evaluate the haemodinamic tolerance to the veno-venous continuous hemefiltration (vvchf) system in patients with systemic inflammatory response sindrome (sirs), and the possible beneficial effect of this technique on the haemodinamics in these patients. material: patient admitted to the icu, with diagnosis of sirs and monitored with a pulmonary artery catheter at the beginning of wchf. we performed a complete haemodinamic study to all these patients (cardiac output, vascular resistanoss, ph and co in arterial and mixed venous blood samples, saturation of pulmonary mixed venous blood, do and vo calculations and temperature) and determined the respiratory mechanics (compliance and pao /fie relatinship) before starting the procedure, after minutes operating with the ultraflltrate branch closed (without filtered fluid production), afler and minutes of zero fluid balance bemofiltration and after minutes of filtration with negative balanos adjusted to the patients conditions. for the statistical analisis we have performed the anova test over the mentioned variables. results: we have not detected statisticaly significant differences of the analyzed variables before the beginning after operating the pun'@ for minutes without filtered fluid production and after minutes of zero fluid balance hf. only temperature shows a meaningful decrease in time. objectives: among many organs, playing the important role in pathogenesis of multiple organ failure, the particular place is taken by the intestine. ~ethods: the study was carried out in dogs !~n"~h pi was modelled by severe operative trauma (ot). the dcm was estimated by the indices values of work time (wt), contraction frequency (cf), mean amplitude of contractions (~ac) and motility index (mi) measured by method of tensography. "sl", created on the basis of sorbit and sodium lactate ( mosm/l), was injected in the dose of .o ml/ kg into v. cephalica antebrachii after hrs of ot. the results of the present study are the evidence of "sl" stimulative action on dcm and are experimental ground for "sl" using in complex therapy of pi in clinic. with splanchnic venous blood pc p.f. laterre p. goffette, j.p. fauville, a. poncelet, p. loneux, m.s. reynaert. intensive care unit, st. luc univ. hospital, brussels, belgium. determination of gastric intramucosal ph (phi) by gastric tonometry using the henderson-hasselback equation is expected to allow the detection of splanchnic ischemia in critically ill patients. because of bicarbonate concentration and acidbase balance influences on the calculation of phi, it has been proposed to use arterio-gastric pco,_ gradient [p(gast-a)co,] to assess splanchnic perfusion. htpothesis : pcoz in the gastric mucosa is in equilibrium with intraluminal co z and with co, in the blood leaving the stomach (mesenteric and portal blood). objective: mesure pco; and ph in portal vein blood and compare its value with pco and phi obtained simultaneously by gastric tonometry. material and method : in a patient ( y.), a fiberoptic catheter (baxter r) was positionned in the portal vein after transhepatic stent shunt repermeabilisation. hemodynamic parameters, do, (vigilance n baxter), gastric co and phi (tonometrics baxter) and portal blood gas were determined at regular intervals. results : sets of data were obtained and are expressed in mean + sd. gastric pco z was , + compared to , + . mmhg for portal pco . phi was . +._ , vs . +._o, for portal ph. no correlation was found for these parameters. p (gast-a) c was . + mm hg vs + . mm hg for p (portal-a) coz (no correlation). there was a good correlation between do e and p (portal-a) co z (r = , ) [figure] but no correlation with p (gast-a) c . obiectives: desaturation is a common finding during haemodialysis (hd). pulmonary oedema might be one cause for impaired gas exchange ( ). the aim of this study was to quantitate the amount of extravascular lung water (evlw) and gasexchange in chronic renal failure patients during and after a regular hemodialysis session. methods: chronic renal failure patients without symptoms or diagnosis of cardiac or respiratory disease were studied at the start (i), at the end (ii) and two hours after (iii) a regular bicarbonate hemodialysis session. the double-indicator dilution method, with indocyanine green and the stable isotope h as tracers, was used to measure evlw ( ). arterial bloodgases and endtidal co were registered. evlw data was compared to a group of renal healthy patients ( ). dcp n evlw, ml -pao , mmhg h~o +, nmol/l control group - -- l _+ "* -+ _+ crfgroup ii -+ ~ +- ns -+ "(" iii +- t _+ ns -+ t ** p < . dcp i from dcp , t p < . dcp li or i from dcp i, :~ p < . dcp ii from dcp i the evlw at the start of dialysis was larger in the crf group than in the control group. the evlw decreased significantly to a level not different from the control group in response to the reduction in weight after hd. pao~ was normal at the start of hd and showed a nun-signficant reduction after hd. paco ( . + . kpa) and etco ( . + . kpa) were unchanged while h o+ decreased and bicarbonate increased significantly. conclusions: the elevated level of evlw at the start of hd did not impair gasexchange. the decrease in evlw did not inhibit the decrease in pao . the reduction in h + followed by a fall in alveolar vantilation is the most plausible cause for the decrease in pao in bicarbonate dialysis. . prezant lung ; : - . . wallin j appl physio ; : - . a. dona~ d. battis& l col~ r danieli, d. achill~ l viglienz;~ c. giov-anaini, p. piaropao~ oblectives: to verify if intraoperative modifications of mtramucosal gastric ph (phi) below the normal lowest value . , can be predictive for important complications, as perforation, sepsis, mof or death. methocls: we have considered patients who andenvent major abdominal surgery. all patients received the same drugs in pre-anaesthasia, the same type of anaesthesia (balanced anaesthesia) and the same treatment with h -bloekers. after the induction of anaesthesia a gastric tonometer was positioned and a catheter was positioned in the radial artery. during the operation, every minutes, the following parameters were measured at the same time: phi, arterial ph (pha), blood lactate, mean arterial pressure. in follow up we considered death and complications happened during the hospital stay, in relation to intraoperative phi falls below . . results: among the patients, had a drop of phi below . during surgery. in three of them this fall was a single episode and happened within the first hour after the begiluting of the operation. after that phi rose to nomml values until the end of the operation these patients had a normal post-operative period, without complications, the other patients had a fall of phi during the demolitive manoeuvres. two paticots of them died. the first had a lowest phi= . and the second . . the first one ~zs operated on for hepatic istiecitoma, suffered a complete del'dseenco of the surgical wound on the th day after operation and died on the th day, the second one was operated on for a hepatic carcinoma had an intraoperative haemorrhage and died ~vo hours after the end of the operation. the other patients with a fall of phi had a lowest phi= . . . . . . . respectively.the first patient,operated onfor sigmoid carcinoma, underwent on a second operation for a transmural necrosis of the colic segment on the th day; the second one, operated for carcinoma of the right colon, had a cardiac ischelnia on the th pest-operative day and a dehiscence of the surgical wound on the th day: the third one, operated on for a sigmoid carcinoma, had melena in h post~ operative da b, and finally the fonrth patient, operated on for carcinoma of the tight colon, suffered a fistula of the surgical enteral anastomosis.all these patients were discharged alive from the hospital. the other patients, who had not reductions of phi ditring the operation, had a normal pest-operative period, without complications. conclusion: phi was able to predict the arising of some complications, probably due to intraoperative ischemic events. we can say that gastric tenometry, for its low invasivi.ty, can be included among the intraoperative monitoring in patients that tmdenvent on major abdominal surgery. (ttd),t"ea~rrerj.~ of hours duraticn. all l:atients nm.'-~ms_(~lly va~ ated in eantrol wcde ard_ la':'ad a a,~m--ganz catheter, with optic fibers for contirums mmsuremmt of svo mic studies were performed, c~e before the hegir~ of hd, c~e rain after the ~, ~ne at the middle, ~ne rain before lhe erd ard one rain after the erd of hd. paired t test ~as used far slatistical eval~ti~n. results: daring i~d there was a significant'reductton (p<o.~) of: c~tr~ venc~s eres~.re ( ve)emm to . ~ ~, ) ~arn'~w capil~ ~f~e pressure (i<~p) fr~n to ~mg hg, ) i~ from to . mmg hg. ~here was also a less pmnameed bat also-slatistics/ly significant r~ucticn (p<o. ) of: i) s~o~ from to patients undergoing surgical reconstruction of the aorta due to anenrysms of its abdominal part may develop transient and sometimes sustained episodes of dysoxia despite the conventional appeoreneas of being adequately resuscitated. indirect masurement of gastric mussel ph (phi) is being widely evaluated as a minimally invasive and sensitive means of assessing the adequaey of tissue oxygenation in these circumstances. the duration end degree of gastric intramucosal acidosis are related to the risk developing injured gastrointestinal tract end its putative consequences, i.e. translceation, cytokine release, organ dysfunction end failure, sepsis end death. measurement of phi is obtained indirectly by measuring pc in the lumen of the stomach with a silicone balloon tonometer (tonometrics, inc., worcester, ma, usa) and the bicarbonate concentration in arlz,,rial blood, end substituting these two values in the henderson-hasselbalch equation. objectives: to evaluate whether perioperative phi changes are predictive of complications end outcome end how they compare to standard haemodyuamic and oxygen trensport parameters. methods: patients ( males and female) urtderwent surgical replacement of abdominal aortic anonrysm with the aortic simple or bifurcated grail. patients were operated on eleetively, had an emergency surgery for raptured enentysm. haemodynamic, arterial ph and bicarbonate concentration measurements were taken before and after induction of anaesthesia, after cross-clamping and declamping of the aorta end at admission to itu. phi calculations ware done at the sime time except before induction, as tonometers were inserted after patient had been asleep. we used pulmonary utilizing a computer billing survey as well as hospital service transfer data from a month period ( / - / ), all obstetric patients that were transferred to the med/surg icu were identified, as well as their diagnoses and procedures. twenty-eight obstetric patients were transferred to the med/surg icu, compared to , deliveries occurring during that time period for a . % rate. the following procedural indications for icu transfer occured: insertions of endotracheal tubes, arterial catheterizations, temporary tracheostumy, and venous catheter. the following medical diagnoses were found: hypertensive/eclamptic episodes, hypotensive episodes, pulmonary embolism, mitral stenosis, and coagulation deficiency. there were four episodes of respiratory failure ( %). the historical rates of respiratory failure from the medical literature seen at a university hospital ore higher than those at our community hospital despite comparable icu transfer rates for critically ill ob patients. objectives: to evaluate the usefulness of several isss used in order to predict risk of death (rd). design: prospective data collection for months in a multidisciplinary -bed icu. methods: data from consecutive patients admitted to the icu from / / to / / were studied. all the necessary informations were stored in a computer using special software for every day computation of three isss (saps, saps ii, apache ii) and of the rd predicted by saps ii, mpm , mpm and odin. data from days of hospitalisation were used for comparative evaluation of isss and rd, while sensitivity and specificity in death prediction (cut off point of rd = %) were evaluated from data collected during the day of admission (saps ii, rpm , odin) or after hrs (mpm ). agreement between rd predictions was evaluated by bland and altman analysis. results:our results were the following: objectives: a) to create and validate software specially designed for the collection of demographic data and estimation of illness severity and predicted rd and b) to provide data necessary for the evaluation of the effectiveness and the efficiency of our icu. design: prospective data collection in a multidisciplinary -bed icu. methods: prospective data on specific physiological variables, selected demographic characteristics, comorbidity and the reason for icu admission were recorded every day for consecutive patients admitted to the icu from / / to / / . data were entered into a portable computer using specially designed software allowing the calculation of usual illness severity scoring systems (isss) and the corresponding predicted rd. results: we studied men and women, with a mean age of years. we conclude that, although observed mortality was higher than predicted rd, this difference was not statistically significant. the fact that the sd of predicted rd was too large, limits the usefulness of isss predictions for a comparative evaluation of different icus. objectives :the importance of objective evaluation of patients prognosis at their admission to an emergency department is clear. the aim of this study was to appreciate the prognosis of patients with the simplified acute physiology score ii (saps ii), and correlate this score to the prognosis and orientations of patients. methods : the score which is a reduced form of saps ii was calculated from clinical variables and laboratory items for patients. sensibili}y (se), specificity (sp) and accuracy (ac) were calculated to evaluate the performances of saps i . thresholds were calculated with the youden's test (se+sp- ). results : patients were admitted in the intensive care unit (icu)and patients in medical units; patients died. the saps ii was higher in patients which died than the survivors ( , + , vs. , + , , p< , ; respectively), the best threshold was , se was de %, sp was %, the ac was / . thus for patients admitted in icu than in medical unit ( , : : , vs. , + , , p< , ; respectively); the best threshold was , se was %, the sp was %, the ac was %. conclusions : these preliminary results suggest that saps ii can be used to determine the short term prognosis and the destination of patients seen in an emergency department. design: data was collected on all admissions over a six month period. all patients had a screening hiv elisa test. confirmatory ifa tests, western blot and flow cytometry were performed on hiv positive patients. the institutional ethics committee considered the major clinical impact of the study sufficient cause to waive the patient's right to informed consent, icu staff and patients were blinded to hiv results. following discharge patients were given the option of being advised of their hiv status. setting: the study was conducted in a bedded surgical icu at a tertiary care teaching hospital. patients, participants: all patients admitted during the period in question were included. interventions: "all patients were treated according to standard icu protocols. there were no interventions. results: most patients were admitted following trauma. there were no patients with aids, hiv positive and hiv negative patients. with respect to the latter two groups, the mean age and sex distribution was similar, there was a significant difference in organ failure ( % versus %, p < . ) and septic shock ( % versus %, p , : ) but no difference in icu/hosp[tal mortality or duration of icu/hospital stay. flow cytometry changes in hiv positive patients were consistent with the quiescent phase of hiv infection. conclusion: while morbidity is higher in hiv positive patients, there is no difference in mortality. hiv status should, therefore, not be an exclusion criterion for icu admission in this patient population. , n= ) and january-march (period , n= ) were studied. interventions: a resident micu team led by a trained intensivist took over the medical care from the primary physicians when the patients were admitted to the micu. the intensivist also vetted micu admissions and decided on micu discharge. in addition, there was a resident respiratory therapist to attend to vendlatory care during office hours. after office hours, the care of the micu was delegated to the on-call team on a rotational basis among the medical departments. results: the patients in the two groups were similar with respect to age, sex, race, source of admission and apache scores. the icu and hospital mortalities decreased from . % to . % (p=ns) and . % and . % (p=ns) respectively in period . the mean icu and hospital stay was also decreased from . __+ . to . + . days (p=ns) and . __+ to . • . days (p=ns) respectively. the improved micu length of stay for survivors in period was statistically significant ( . • . days vs . • . days = . ). there was no significant differences in the vse of peritoneal dialysis ( . % vs . %) and mechanical ventilation ( . % vs . %). however, utilisation of intra-arterial lines and pulmonary artery catheters increased from % in both to . % and . % respectively in period . conclusion: the duration of critical illness was reduced in period . hence, we believe that the closed |cu which was staffed by an intensivist and had the services of a respiratory therapist was beneficial for the care of the critically ill. the intensivist, was also more likely to utilise invasive monitoring. in the absence of liver transplantation, intensive care for patients with acute hepatic decompensation arising from alcoholic liver disease (ald) is indicated only for those who are likely to benefit from conventional means of organ support. we have attempted to elucidate potential risk factors and the efficacy of organ support in relation both to hospital outcome and icu costs so as to allow the earlier identification of relatively futile intensive care in this group of patients. methods: over a period of one year, ald patients ( males; females; median age years, median apache ii score ; hospital mortality %)with severe complications ( [ %] with bleeding oesophageal varices, [ %] with hepatorenel failure, [ %] with respiratory failure, [ %] with septic shock, and [ %] others) were studied in our liver icu. organ system failure, daily therapeutic interventions and icu costs were assessed using a patient management system (riyadh intensive care program). results: whilst survivors had a significantly lower admission apache ii score compared with non survivors (medians and , p< . ), or more organ systems in failure in the first hours of icu admission was associated with a % ( ) mortality. mortality was also related to child's grading and the numbers of organs supported. of the patients who received more than one form of organ support only one survived. organs supported mortality a (n= ) % none / ; % b (n= ) . % one / ; % c (n= ) . % two or more / ; % the icu costs for the patients were only s but s ( %, patient days) was utilised by the patients who died, giving an effective cost per survivor (ecps) of s . although the cost of treating the patients with or more organ systems in failure on the day of admission was s ( % of the budget) the ecps was s . conclusion patients with ald who have or more organ systems in failure early in their icu course have a poor prognosis and in the absence of liver transplantation, traditional strategies of organ support are ineffective. this begs the question whether such costly care is appropriate as although the ecps in this sub group is comparable with other patient groups with multiple organ failure, their outcome is considerably worse. objectives: to evaluate the economic impact to the healthcare sector of using dopexamine hydrochloride infusions to deliberately increase perioperative oxygen delivery in high-risk patients. methods: effectiveness data were obtained from a controlled clinical trial in which surgical patients were randomly assigned to either a control group (n = to receive best standard optimal fluid resuscitation perioperatively, or a protocol group (n = ) to receive, in addition, an infusion of dopexamine hydrochloride to increase the perioperative oxygen delivery index to greater than ml/min per square metre. resources consumed by patients during treatment were recorded prospectively and costs of resources at / prices were obtained retrospectively. cost-effectiveness ratios were estimated by dividing the total cost for each treatment group by the total number of patients in each group and by the clinical outcome of mortality days postoperatively. results: in the protocol group, there was a % reduction in mortality days postoperatively (p = . ), a significant reduction in the number of complications (p = . ) and a reduction in length of stay in the icu and surgical ward. the average cost per protocol patient to achieve a . % survival rate days postoperatively was s , , resulting in an average cost of s , per surviving protocol patient. the average cost of a control patient was s , to achieve a . % survival rate days postoperatively, resulting in an average cost of s , per surviving control patient. the use of dopexamine to deliberately increase oxygen delivery perioperatively generated a cost saving to the nhs of s , per patient together with a % reduction in mortality at days postoperatively. hence, the cost per surviving protocol patient was s . less than the cost of a surviving control patient. conclusion: the additional cost of dopexamine in protocol patients was offset by a lower incidence of complications and a shorter stay in the icu and on the surgical ward. hence, increasing oxygen delivery perioperatively in high-risk surgical patients saves both money and lives. objective: although king's college criteria are widely used, indication and timing for liver transplantation in acute liver failure is still far from certain. long-latency sensory evoked potentials -a proven measure of metabolic brain dysfunction (grimm et al. lancet ; : - ; madl et al. lancet ; : - ) -are markedly affected in patients with acute liver failure. serial sensory evoked potential recording should provide very useful information for the management of patients with acute liver failure. methods: recordings of standard bilateral sensory evoked potentials were performed in patients with acute liver failure. findings were focused on cortical n peak -a stable negative deflection occuring • ms after median nerve stimulation in healthy subjects, which can be recorded by skull electrodes over the sensory cortex. results: nine patients recovered spontaneously, patients were referred to emergency liver transplantation, and patients died. in all patients who recovered spontaneously, n peak was detectable between and ms. all patients who were referred to liver transplantation and of patients who died, developed a loss of a prior detectable n peak during the course of acute liver failure. objective: to determine high risk arid low risk patient groups in a medical intensive care unit regarding short term and long term outcome. methods: data on all admissions of the year were collected prospectively. according to their mode of admission patients were classified as admissions by the physician staffed ambulance service (as), admissions through the emergency department (ed)i referrals from non-intensive care wards (ni), and secondary referrals from other hospitals (oth). outcome was assessed in terms of in-unit mortality, in-hospital mortality, and long time mortality. patient groups were compared using the \ -test. life table analysis were per{ormed by kaplan-meier method comparing patient groups by log-rank test. the software spss for windows . . was used for statistical calculations. results: in-unit mortality: / patients ( . %) --oth . % > as . %> ni . % > ed . %; p = . . in-hospital mortality: / patients ( . %) --oth . % > ni . % > as . % > ed . %; p = , . mean survival time in days after discharge: as < ni < oth < ed ; p = . . conclusions: despite an excess in-unit mortality of secondary referrals from other hospitals the iongtime course of this special patient group is not different to others. solsuam, j, marrugat*, g, mirs, j, nolla, a, vazqu~z-sanchez, l alvamz, ~ioio s xndioina i~siw. ir~itate l(~icipal da l~sti~isn l~di~*, ~ospits dal objective: to study the influence of modifiable variables (complications derived from therapeutic activities) on the prognosis of ~atients admitted to the icu indapemently on thn severity of illnsss. patients am methods: between january asd ]lay data from , patients over years of aqe who retained in the icu for mare than hours ~ere pr~pectively regiatered. a cohort st~ly with follo~-~ nf patients durin~ ~eir stey in the hospital was deni~.el in all patients, reasons for a~issien, principal diagnosis sad severity of illn~s moasared by the saps scare vare recorded. fastens affecting patients' outcome that my be proventsd or modified included technical :omplisafioss, heapital-acqnired infections and in~pro~riate therapeutic decisions. a logistic regression model was used to assess the relative risk (l~} for in-heapital mortality adjusted for each variable. results: ic~ mortality ~s . % and in-hospitul mortality . %. patients who died showed a higher spas score then survivors ( , ~ i ,i). after adjusting hy severity of illness, co~;licetices that statistically increased the risk of in-hospital death were septic shock secomery to hoapitul-acqdired infection ( ~ . ; % el, . to . ), pmo~othor~x related to mocasnical ventilation (@ . ; % cl, . to . ) and delay in the insertion of a fln~-quidod catheter (ii~ . ; % ic, i.i to . ). col~lusien: registration of complicaticas derived from therapeutic activities is a valuable tool far quality central in the icu. g, ~i~ , j.l mle~ma, j, ~amqat*, j..~lla, a, vazquez-saltemz, f, alvamz , servioia de nndicina l~siu. i~stitutu ~icipal de ln~sti~acidn ~ i:a*, hospital dsl objective: to dstsr~ine the incidence of self-extebatien and its effect on ~ortality. patients and ]~etheds: betveen january and april , all i~tiente in whom selfextubatien w~s registered were inclnded in a prospective study. patients were divided into @nee who needed r~intabatinn within hoers and those who did not. in all patients, dsmoqraphie and ciinical data were recorded as well as icii mortality, in-hoapital mrtality and severity of illness according to saps score. eta were analyzed usi~ the cbj-square test for cathgorical verinbls, the analysis of varianc~ (anva) for aontinuc~ ~ria~les and a leqi tic regression anal~is to estimate the relative risk (iiii) for mortality as result of celt-nxtt~ation after adjusting for severity of illness. results: a total of intnmtsd patients amre stndied. self-extu~atien occurred in ( . %) patients and . % required reintuhot~pn. when a co,arise was made between patients who did not required reint@atinn and patien~.s who did, statistically significant differences in eqe ( . v_s . years, p = .~ ), ~verity of illness ( . ~ . spas score, p = . ), dia~isstia category ( s. % v_s . % of patients with res~iratury conditiono, p = , } and mean length of stay ( , ~ , days~ p = . ) were fo~m, a~ter ad~sti~ for severity, patients with self-ext@atinn who did not reqnired reintalatien showed a . iir for mortality ( % ci, .i to . ) as co~arod with patients in when self-ext@ation did mot occur. conclnsien: self-~extamtice that does not require reint@ation is associated with a isamr in-hospital natality probably dt~ to a prolonged period of weaming. patients' admissions to ices am often delayed doe to the shortage of beds available. @ile amaltieq icu admission, these patients are treated in observation nits of @e emergency services which bare ,either tile structure nor the trained ~reomenl that are available in leb~. objective: to daterdno the effect on the patient's proqusis of a delay in tile admission to the icu when criteria for icij admission are fulfilled. ~terials and methods: between jme am l?ece~ber all patients who fulfilled criteria to be almittod to the ic who for waste~r reason retained in tile observation unit for more than hours were included in a prospective stedy. in all patients, des~raphic end clinical dabs amre recorded as well as severity of illness aencrdi~j to saps score. a cesucontrol dasi~ was eend with a total ss~ln of , patients who suffered no delay is admission to icii over a period of years. data wen analyzed using the chl.-squ~re test (to aeons the association hetwenn in-patienty mortality end categorical vari~lns) and a maltipln logistic reqression model to sstimta odds ratio for) for in-hospital mortality as result of delay in icy admission as compared with early ad~issi| after adjusting for severity of illness end use of assisted mchenical ventilation. ~ &ults: a total of patients remained in the observation nit for more than hours with a del w in igd admission of . _+ . hoers. assisted mechanical ventilation was requited in % of patients and only monitericatien in %. itsse patients were cspared with ntients from the tet~l sample ratchod by age, sp~ score and rennoss of admission. in-hospital mortality for cases warn % as compared with . % for controls (p = s). after adjamtilg fen spas, age and mobamioal ventihtien, no statistically significant differences between both ~renpa were foam, altho~b there was a tendency towards a higher mortality amen@ patients with delay in icu admission (or = . ; % ci, , to , ). conclnnien: ~se findings suggest that prognosis of critically-ill patients is no worse as a result of admission to the loll being deln~d for borers. all data appropriate for the calculation of the apache ii score (aps) together wi'th other specific cardiac details relevant to these .patients were collected daily, verified and enter~ into a computer database. results: patients were studied. six patients died and five of thee underwent cardiac surgery. the mean aps was for survivors and t for non-survivors (p < . ). the mortality ratio was . and the major markers of mortality were apache ![ score, presence of chronic ill health, mean duration of ventiiation, mean length of icu stay and need for emergen~ surgery. sixteen percent ( ) of icu bed days were occupied by % of patients (non-sarvivors) which resulted in cancellation of cardiac sot#cat sessions in momhs. conclusions: this study concludes that apache t could be used as an audit tool in a cardiac surgical icu and demonstrates the severe compromis~don of cardiac surgical throughput by a few non-survivors, organ to determine the number of organ failure free days (offd) in a cohort of survivors and non-survivors with sepsis syndrome followed over a day period. ) to determine sample size requirements for clinical trials utilizing a increase in the number of organ failure free days as the primary outcome as opposed to mortality. methods: beginning december through to april , patients who met inclusion criteria of the "cardiopulmonary effects of ibuprofen in sepsis syndrome" and who did not have hiv/aids. brain death or moribund state were prospectively identified. presence or absence of failure of organ systems (pulmonary, cvs, renal, hepatic, gi, hematologic, & cns) was recorded daily until death or until days. a score of one was assigned to each organ system free of organ failure in patients still alive, ie, maximum daily off score= , maximum day off scorn= , sample size estimations were performed for variable detectable differences in off scores (delta). alpha was set at . (two-sided), with n/group = [(z a +z b ) o conclusions: a clinically relevant increase in off days may be detected with as small a sample size as to patients per group. this represents a significantly smaller sample size than needed to detect a change in mortality from % to % ( % relative risk reduction) where the n/group= . scoring patients in this manner prevents a lethal inte~entien from providing an improved organ failure score. in addition, an intervention that prolongs survival must also provide greater organ failure free days in order to be counted by this scoring method. survival as an outcome provides no information about the quality of that survival. off days provides a measurement of burden of illness. interventions which lessens this burden may be just as valuable as those that decrease mortality by providing a measure of the quality of survival and by decreasing costs of care. they may also prove to be an accurate surrogate marker of mortality. the advantage of this approach is that the event rote is much higher and sample size requirements are subsequently smaller. this would mean that clinical trials can be completed faster and at lower cost. outcomes such as mortality could then be assessed at a later date utilizing recta-analysis. we suggest that the use of off days is a valid outcome measure that may be utilized in clihieal trials of sepsis syndrome. the icu is perceived by many as being a stressful environment for both patients and staff. stress has been defined in three ways: a stimulus producing a particular response; the physiological and psychological response to a stimulus; an interaction butwom an individual and their environment. stress is currently thought to be a dynamic system of stimulus and. response which takes into account the individual's perception of the stimulus and their ability to respond effectively. stress may, therefore, be positive and allow personal development but an individual unable to respond effectively to a stimulus will experience negative effects or strain. critical illness is an intense stimulus to which the body needs to respond effectively. physiological responses are vital and most of intensive care involves supporting these. alternatively, blocking them, for instance with atom(date, increases mortality. psyehological responses are also vital but often poorly appreciated because of communication problems. many of the problems patients experience in an icu are evidence of psychological strain. this can be exhibited in various ways, for instance, anxiety, depression, passivity and confusion. dealing with critically ill patients is perceived as stressful. we recently studied occupational stress in our icu. most aspects of intensive care were not generally perceived as stressful indicating a self-selectien of icu staff. the most stressful aspects of icu work for nursing staff were the structure of the organization and career opportunities. medical and nursing staff had different stressors and different coping strategies. support for occupational stress, therefore, should focus on the individual and concentrate on information and communication. atmosphere, and especially at intensive care units, we face up to daily decision making. in most cases these are taken on the basis of personal opinion and the processing of a very limited amount of information. rising need to optimize the results of medical attendance becomes necessary to set structured system of d@cision making in which ethical basis have a sp@dial significance in view of next considerations: -we live into a pluralist society in which the importance of values is different. -most persons consider health as the first value only in the event of illness. -medical resources available are limited, whereas medical, attendance demand from population increases in a way many people consider it unlimited. in consequence, it becomes necessary to set up priorities in patients treatment. ehtical basis that rule decision making are essentially these ones: i. beneficence: to provide the patient that is being treated the highest profit. . non maleficence: it is our first duty to avoid hurting or damaging the patient."primum non nocere" . autonomy: in every particular medical attendance, the patient has ability to decide by himself. . justice: as equity: to provide the same treatment for those who have the same pathology, ignoring another factors such as age, sex or race. severe application of these principles can cause difficulty, which resolution requires a systematization of decision making. ( - ) . the lenght of stay between survivors and non survivors didn "t show statistical significance (p = . ). the mean aiii score when considering all admissions was , ( - ) . the initial score between survivors and non survivors showed ststistical difference ( . vs . ) respectively (p < . ). univariate logistic regresion analysis demostrated a % increment in death probability for every points augmentation in the aiii score with a sensitlbity of . % and specificity of . %, the roc curve showed that the best cut off point for death prediction was points with a sensitivity of . % and specificity of . %. if a patient is classified as high risk (> ) the bayesian analysis showed a . probability of death and for one class(fed as low risk (< ) a death probability < %. conclusions: the first day aiii score in this population showed to be a good discriminator between survivors and non survivors, and the risk of death augments as the aiii does. in this population an aiii score > points is asociated with a greater risk of death. using the aiii score in conjuntion with the clinical judgement will help clinicians reducing uncertainty in the every day decision making and better predict outcome, the results from this study should been taken with caution because the data were obtained from a small sample. objective: the quality of life has been considered a "uniquely personal perception" resulting from a mixture of health related factors and social circumstances [t. m. gill, jama , : ] . the aim of this study was to evaluate two measures of pqol in intensive care unit (icu) admitted patients. patients and methods: during icu stay and six-months after hospital discharge, co-operative icu admitted patients were directly interviewed about their pqol. we administered ftrstly the uniscale (pqolu) [sage et al crit. care med. , : - ] and then a step verbal scale (pqolv): best, good, fair, poor, worst. of the studied patients, at the first interview, were able to use both scales, but ( . %) understood only the verbal one. at the second interview, patients were not able to answer, used both scales and only pqolv. statistical analysis was performed using wilcoxon signed ranks, spearman rank correlation, student's t and chi square tests. results: of all cardiac surgery pts, pts ( . %) died in icu. they were males ( . %) and females ( . %). their mean age was (+ ) years and mean ef was . (+ . ). nineteen pts ( %) had low (< . ) preoperative ef. mortality was . % in the coronary artery bypass grafting (cabg) group (n= ) and . % in the valve replacement (vr) group (n= ). in the cabg +vr group, mortality was . % (n= ), and . % in the remaining pts (n= ). cardiogenic shock was the sole cause of death in pts ( %), septic shock in pts, whereas sepsis in combination with ards in pts, sepsis and stroke in two pts. in addition, pts died from cerebrovascular accidents, one from ards and one from pulmonary embolism. the pts who died in the icu had a significantly longer bypass and aortic cross clamp time and received more blood transfusions (p< . ) than a matched control group that survived to icu discharge. the duration of mechanical ventilation and length of icu stay were greater in the pts who died in the icu than in the control group. conclusions: . although cardiogenic shock is the main cause of death ( %)in cardiac surgery pts, sepsis and cerebrovascular accident are relatively frequent causes. . patients who died in the icu had longer bypass and aortic cross clamp time and received more transfusions, compared with the control group. . although renal or hepatic failure contributed to death in some pts, they were not the primary cause of death in any patient. objectives: evaluate the acute and follow-up outcome of patients (pts) treated with primary ptca (without prior thrombolysis) in acute myocardial infarction (ami) after and up to hours after onset of typical thoracic pain ("late" primary-ptca). methods and patients characteristics: from / to / consecutive pts with ami were treated by primary ptca in the wuppertal heart center pts ( , %) were admitted to our hospital > hours and < hours after symptom onset with ongoing chest pain and typical ecg-changes.mean age was years ( - ). pts were male, four female. % had an anterior wall myocardial infarction, % suffered an inferior/postero-lateral wall myocardial infarction.two pts were in cardiogenic shock at admission. singlevessel-disease was documented in . %, multi-vessel-disease in . %. average time of onset of pain to recanalisation was min ( - ). angiography revealed timi-flow in . % of the pts, timi-flow i in . %, timi-flow ii in . %. average follow-up (fu) period was months ( - months). timi iii lv-ef ~ -day major late re-late flow p.i.* aeute/fu mortality bleeds infarction mortality . % %/ % . % . % . % % early mortality occured in the two pts, who were in cardiogenic shock at admission no pt required emergency coronary artery bypass grafting.restenosis > % was seen in % of the pts. conclusions: "late" primary ptca achieves a favourable high recanalisation rate of about % (timi ill-flow) in our study group. additionally, there seems to be a trend for lv-ef improvement in follow-up. early high mortality is influenced by the patients admitted in cardiogenic shock. there might be a trend for increased major bleeding complications. objective: to assess the validity of saps ii (new simplified acute physiology score), comparing it with the previous version, (saps), in a sample of patients recruited by giviti, a network of icu's representative of the italian icu system methods: measures of calibration (goodness-of-fit statistics) and discrimination (receiver operating characteristics curve and area under the curve) were adopted in the whole sample and across subgroups differing in relevant prognostic characteristics. of the patients recruited during one month period, a total of patients were included in this study. for the purpose of the comparison of the two scores, patients with less than years, or having cardiac surgery or staying in the icu less than hours were excluded. vital status at icu discharge in the whole sample and at hospital discharge in half cases wher adopted as outcome measure. re$ ~: saps ii fits the data equally well compared to the older version (goodness-of-fit p= . and in the new and old versions, respectively) but its performance is somewhat better in terms of capability to distinguish patients who live from patients who die (areas under the curve . and . , respectively). furthermore, saps ii is better in terms of uniformity of fit across relevant subgroups, although substantial over prediction of mortality was observed in trauma patients and in patients admitted without organ failure to be intensively monitored. saps ii performed very wet] also in the subsample where hospital mortality was the dependent variable.satisfactory measures of calibration (goodness-of-fit p-- . ) and discrimination (receiver operating characteristics area= . ) were observed. c nr saps ii, a multipurpose scoring system developed in an international study, retains its validity in this independent sample of patients recruited in a large network of italian icus. although it has shown a good performance when adopted to predict icu and hospital mortality in the entire sample, further investigations are warranted. the observed over prediction of mortality in a few subgroups indeed call for a through assessment of the impact of confounders and biases on model performance when saps ii is adopted in samples that do not reflect the "average" icu patient. objectives: ) assess the effectiveness in a group of intensive care units by means of a quality performance index (qpi); ) assess the efficiency by means of a resource use index (rui); ) evaluate the performance of individual icus with respect to both indices (clinical and economical) while controlling for severity of illness. critical from ucis in catalonia patients alearic islands have been included in the study. inhospital mortality and weighted hospital lenght-of-stay (los) have been considered the outcome variables. severity of illness has been measured with the mpm ii at admission. in each icu, expected mortality has been obtained adding the probabilities of dying for its patients. expected los has been estimated adjusting a second order polynomial to the severity of illness. performance indices have been obtained by dividing the observed by the expected outcomes. re~ult~: the overall qpi was . and it ranged from . to . in the icus. the overall rui was and it ranged l~ont . to . . there was not a trade-offpattern between clinical performance and resource use. objectives: teaching hospitals often provide [cu care across a variety of specialized services. overall, this approach appears to result in the best risk adjusted survival rates, but at the highest cost (critical care medicine ; : - ): recently, there has been increasing focus on markers of overall hospital performance. however, in large teaching institutions, such markers may fail to detect intra-institntional variation at a large tertiary care medical center. methods: first intensive care unit (icu) day, acute physiology and chronic health evaluation iii (apache iii) and active therapeutic intervention scoring system (tiss) data were collected on random admissions to specialty icus with beds (range - ) between february i and december l, . post-operative solid organ transplant recipients were excluded. units included general medical, general surgical, and trauma, neurosurgery, cardio-thoracic surgery, and coronary care units. data were analyzed for risk adjusted outcomes: icu and hospital mortality and length ef stay (los); risk of requiring active cu treatment; and icu readmissinn using apache iii risk prediction models. results: the study icus cared for a diverse group of patients. mean apache iii scores ranged from . - . ; predicted risk of hospital death ranged from . - . %. standardized mortality ratios ranged from . to . with icus performing significantly better and performing worse than predicted (p< , ). los ratios and icu readmission rates ranged from . to . (ns) and . to . % respectively. patients predicted at low risk of requiring active icu treatment ranged from , to . % conclusions: there was wide variation in the mean level of patient severity between icus. after controlling for this severity, outcomes also varied widely. no clear pattern of overall institutional performance was evident. these data suggest that efforts to assess performance, improve quality, and maximize efficiency must be focused within individual units. programmatic evaluation of outcome allows for focused review of the processes of care contributing to good outcome (best practices) and where to focus ongoing quality improvement and cost reduction activities. background and method : we compared icu mortality in different age groups presenting with the same severity of disease. we assessed severity of illness by the physiological day -apache~ (physio-aa) score (thus excluding the age related points). for each of the following physio-a n score intervals ( - ; - ; - ; - ; > ) , we compared tcu mortality within age intervals (< ; - ; - ; - ; - ; > years - , - , - ) . in these groups mortality may be twice higher in the > years patients than in the _< years. mortality does not vary with age in low (physio a n = - ) and high (physio a n = > ) risk groups. in the low risk group, mortality is low in all the age intervals because of the begninity of illness. in the high risk group, extreme severity of disease probably blunts the impact of age and leads to high mortality rates in all age intervals. introduction: to access the actual social/clinical outcome of the patients who undenvent intensive care therapy oct) is rather difficult, quality of lilr is not easih.' defined and ohserver subjectivity is a prime factor in the evaluation. mortality ratio after discharge must be established and its causes understood. obieetives: the propose of this stud)-is to look into the mortality ratio that occurred on a series of patients that undorwent ict at our unit from of the ~iew point of severity of the original illness and the diagnostic groups. material and methods: during the period of one )-ear ( ), patients were treated at the unit, of them died, and ~ere not matched in our series because os incumpletc records. thirteen patients died in hospital after their reference to other departments, twelve patients were lost after discharge. thus. at the end. only patients were evaluated on the fu. the, were classified into the follov ng three groups: acute medical, elective surge d and acute and emergency postoperative. the patients were seen at , and months after discharge. the, were evaluated in accordance to their abili~, to being self supported in their daily life and capecity to fully return and hold to their pre~ ous jobs. apache scores were evaluated for each of the three groups and correlated to the icu dead, hospital dead, and mortality after hospital discharge, spss package was used for statistical analysis. remlts/conclasions: data shows that / patients died after discharge from the hospital, of ~itch nine died in the first three months. seventy-eight per cent of the patients were fully self supported in their daily life and % showed some kind of handicap. fosty-nine per cent of the patients wore on retirement either due to age or some form of chronic disease, when admilled to our unit. thirty-two peg cent had not been able to return to work, because the" were incapacitated on discharge. only % had return to their fully jobs but the period of the stu~, is not enough for all of them to be fully physically recovered. preliminmy statistical analysis shows us significant differences among groups. the aim of the present study is to compare the prognostic performance of five general severity indices ou coronary patienta and to find out if a proper ntatistical hundling of these indices could provide better results in these patients. methods: saps ii, mpm ii (mpm ii i mpmp ii ), apach ii end gaprik were evaluated o~ patients with acute myocardial infurction admitted to intensive care units from catulunye. calibration and discrimination were calculated for each index. calibration was calculated by th bosmer-lemeshow test. discrimination was evaluated by the area under the relative operating characteristic (roc)curve. if a model did not show a good performance it was customized using multiple logistic regression. finally, tworeduced models were developed, one fro~ the mpm series (mpm ii cor) and one from the group apache-saps (sapsiicor).their performances were again evaluated. results: discrimination was high enough for all models. neverthelees, oelibration of apache ii, saps ii and mpm was not satisfactory. thus,mpm ii , saps ii and gaprik were customized for coronary patients using the logits of both models, and obtaining good calibrations. mpm ii , and apache-saps were adapted and reduced to (mpm ii cor) end to variables (sapsiicor), respectively . both models showed better oalibrutions end discriminations than the original models. conolusion| models developed for multidisciplinary patients show a good discrimination when applied on aoronar i patients, but some needed customization in order to improve calibration. the number of variables of the principal model can be reduced (even to or variables) without loosing prognostic accuracy. objective: to compare the ability of two methods to predict outcome for intensive care patients. methods: we included consecutive intensive therapy unit (itu) admissions with an itu stay> hrs in a month prospective study (exclusion criteria: burn injury and age < yrs). data were couectsd applying the criteria described by the developers [ , ] . the definition of coma (mpm ii) was modified and the best assessment within in's, rather than the admission score, was used. statistical analysis included classification tables and receiver operaung characteristics (roc) curves to assess discriminative power, and lemeshaw-hosmer statistics and calibration curves to test accuracy of prediction. results~ average abe was yrs (ranse: - ) with a male:female ratio of . : . the actual hospital mortality was . %, mean predicted death rates were . % (mpmz ii) and . % (ap hi). non-survivors had siguitlcanfly higher predicted risks than survivors applying both methods (p< . l, t-test). the total correct classification rates (tccr) for apache iii were bett~r for all decision criteria applied (tccr, decision criterion %: apache ]/i . %, mpm ii . %). the area under the roc curve was . (ap iii) and . (mpm ii) confirming the better discrimination of apache ill. accuracy of risk prediction was similar for both models (ap nl ~ - , mpm b ;( - , lemeslmw-hosmer). showing some fluctuation, calibration curves lay close to the ideal line for predicted risks -< % with increasing deviation for higher risk groups (s. figure) . apache iii underestimated the risks of hospital death for almost all risk groups (curve above diagonal), whereas considerable overestimation for predicted risks > % ceenred with mpm~ii. objective: to assess the goodness-of-fit of the apache iii model for british itu patients. methods: we prospectively studied a cohort of adult patients consecutively admitted to a medical-surgical itu over a period of months. patients with burn injury, age < yrs and itu stay < hrs were excluded. using a eomputerlsed database, we routinely recorded hrs apache ill scores. predicted risks of hospital death were computed by critical audit ltd, london. accuracy of risk prediefion was assessed by hosmer-lemeshaw chi square (;( ) statistics and calibration curves [ ]. discrimination was tested employing classification tables and receiver operating characteristics curves (roc). restths: the mean age of the male and female patients was yrs (range: - yrs). of these patients, % were medical admissions, % were admired after emergency and % after elective surgery. the observed hospital mortality was . %, the overall mean predicted death rate was . %. mean predicted risks were siguifieanfiy greater for nonsurvivors ( . %o) than for survivors ( . %, p< . l, t-test). apache iii showed good calibration (z -~ , lemeshaw-hosmer). however, the calibration curve lay above the diagonal for almost all risk groups reflecting the tendency to underestimate actual mortality (s. figure) . the best total correct classification rate (tccr) was . % (decision criterion: %). the area under the roc curve was . % confirming the good discriminative ability of the model. objectives: the aim of this study is to point out the discrepancies between needs and actual treatment of less severely ili patients admitted in italian intensive cam units (icus) requiring only intensive monitoring, and verify the substantial likelihood of data comparing those collected from a national short term study with a regional long ternl use. ~: less severely ill patients ("observed patients") were only monitored; they did not require intubation, even if for a short period (less than houm) or major cardioeiranlatory supports, and were neurologically normal. epidemiologieal national data were obtained from giviti group (gruppo italiano valutazione interventi in terapia intensiva); this cohort study, collected patients, in two months in summer in all over italy. regional data were echieved in a three years entlection ( -i ) in lombardia' icus from archidia group (arehivio diagnostieo), including patients. mortality, severity score, diagnostic category and some typical intensive procedures were analysed and compared in both studies. patients' disgunstie categories were defined as surgical, medical and trauma, according to the main diagnosis and the presence/absence of surgical procedures. rr observed patients account for . % and % of all icu's patients respectively in national and regional data. very tow mortality rate was found in national data ( . %) and extremely low mortality in regional data ( . %). in both studies mortality, s.a.p.s. and length of stay were much lowor in "observed patients" than in general icu's population (mortality: . % and . %; .a.p.s. score: . and ; iength of stay: % and ). homologous distribution of patients in the two studies was noted for what concern their diagnostic category, aside from a slight prevalence of tranmatised patients in the giviti study. in the two groups the surgical patients were respectively % vs. %, medical patients were % vs. % and traumatised were % vs. %. % of "observed patients" in national study and % in the regional did not received any intensive procedure. only a minority of these patients availed haemodynamie eonu'ol with swan-ganz or renal haemofiltration. conclusions: these results underline that about one fourth patients admitted in italian icus benefit an oversized slructure i, relation to the real needs of their pathology. in hot more than % did non received any advanced treatment and mortality and s.a.p.s. score were substantially lower respect to general population. the results obtained from these two studies are similar, suggesting an uniform distribution of the case mix in italy, even if a different recruitment period and a different gengraphieal distribution were used. some discrepancies in the two studies were found in the diagnostic categories moreover regarding the tranmatised patients ( % vs. %); this can be explained from the seasonal (summer) characteristic of the national study. mutuality, yet very low, is different in the two groups, but these data do not allow any definite explanation. finally these epidemiologieal survey suggest need of further studies settling more strict criteria of admission in icu. this study aims to evaluate patients outcome, quality of care and effectivity of therapy in our intensive care unit. the main goal was to indentify factors that the most influence that outcome. during . the authors collected data of patients outcome and predictor variables. overall mortality rate was , %. the most common causes of death were infection. the diagnosis of sistemic inflammatory response syndrome (sirs) and multiple organ dysfunction syndrome (muds) significantly correlate with death ( %). average length of stay was . days ~. % patients died in the first ten hosiptal days and only % after days. age was directly correlated with death % of dead were older then sixty years. an analysis of physiological variables showed that serum levels of gl~cose ( %) and natrium ( %) were in optimal physiological values. serum proteins ( %) and haemoglobin ( %) levels were inversely related to death. multivariate showed that alveolo-arterio difference in content was the most informative of all mortality predictors (mean value , mmhg in % patients io>mrnhg). factor that most influence the patients outcome was infection (sepsis) and muds. use of predictive indicators of outcome in critically ill patients may help to assess treatment regimens and to compare patient groups. acute physiology and chronic health evaluation (apache if) score (crit. care had. ; : - ) and the sepsis score of elebute and stoner (br. h surg. ; : - ) have been used, objectives: to compare sepsis score and apache ii score in predicting outcome of critically ill patients. methods: overall survival during the past years for patients in our icu was calculated = % (prior probability). the outcome of patients who were admitted to our icu for > hours was observed. apache ii score on admission, patient predicted risk of death (apache ii risk) and the sepsis score on the first day of antibiotic course were prospectively recorded. discriminant function analysis of the scores in relation to outcome was performed. results: apache ii and sepsis scores in the survivors were significantly lower than in those who died ( . i . v~s . • . and . • v's . • . respectively p < . ). correct prediction of outcome by each score is shown in discussion and conclusions: although both scores have been previously evaluated in predicting outcome of icu patients, studies of the sepsis score were conducted in small numbers of patients or involved additional measurements not routinely available. this study demonstrates that the sepsis score alone or in combination with apache ii score is more effective than apache ii score in predicting outcome. objective to test the hypothesis that resuscitation titrated against gastric intramucosal ph (phi) improves survival in critically ill patients as suggested by gutierrez et al~. method emergency admissions to the intensive care unit were randomized into control and intervention groups. in the control group phi was measured at , and h while in the intervention group phi measurements were made hourly for h. both groups were managed according to the same guidelines to achieve the following targets: mean arterial pressure > mmhg, systolic arterial pressure > mmhg, urine output > . /ml/kg, haemoglobin > g/dl, blood glucose < mmol/ , arterial oxygen saturation > % and correction of uncompensated respiratory acidosis. if the phi was < . after achieving these targets, or after maximal therapy to achieve the targets, patients in the intervention group were given fluid to ensure an adequate cardiac preload and then dobutamine at then mcg/kg/h, titrated against phi. this additional therapy was continued until h after entry into the study. in each year patients were subdivided in two series with random selection, so that the st series contained abeat / and the nd / of the patients. the st series of all the years constituted the devdoping data set and the nd series the validation data set. with data of the st series ( patients), we created the predictive model, using stepwise logistic regression (bmdp, usa). each patient has been evaluated in die st, th, th and th day, calculating for each lime the apache ii score (for a total of records), independent variables were, besides time and apache ii of the time ( michaloudia g,, melissaki a., alexias g., gogafi c., kolotoura a., krimpeni g., pamouktaoglou f, filias n. objectives: to determine the medical staff's attitude towards various ethical issues methods : between january and february , anonymous questionnaires were sent to intensive care units, all over greece. results : questionnaires ( , %) were replied and returned back. of them , % were answered by male and , % by female. the doctors replied in the following rate : , % aged up to , % aged between and , % aged over . questions were answered and were divided into main topics, as following: . admission criteria: limited bed availability was the main cause for refusing admission in , % of icu's. , % evaluated each case's viability and only , % used some prognostic score system. , % of icu's accepted all cases and a significant percentage ( %) gave in to pressure coming from their colleagues ( , % female and , % male). . informing the patient/relatives: only , % was willing to tell the whole truth, while , % had given selective information.. in the case of iatrogenic incident, , % withheld it, because either they feared legal implications ( , %), or lost of trust ( , %). doctors are asking consent from the patient and/or his family, in order to include him/her in research protocols, in a rate of , %, while only , % found informed consent necessary for the proposed treatment procedure. . withdrawal of therapy/dnr orders/organ donation: , % were willing to withdraw complex treatment in patients with short life expectancy, except of administi'ating intravenous fluids, feeding and analgesics. in , % such a decis~n was unanimous, while the percentage of those carrying it out was , % ( , % female, , % male). in case of brain stem death , % ( , % female, , % male) withdrew any life support. , % would like therapy withdrawal to be legally established, while only , % would perform euthanasia, if there was substantial legal cover. for these cases, relatives' consent was considered to be necessary from a percentage of only , %. , % considered organ donation to be a necessary proposal, while , % refused to ask the patients' relatives for an organ donation, either because they didn't have the psychological strength for it ( , %), or because they doubted the procedures' objectivity ( , %). note: in greece, icu beds are less than % from the total number of hospital beds available. only a percentage of - % of these admissions comes from the same hospital, with a potentially direct evaluation. usually an icu doctor has to be informed through the telephone. finally, employment conditions in greece are such that any changes of the medical and nursing staffare limited. conclusions: the mathematical model we found has been validated also in the second series and the discrimination capability increases with time. using this model we can evaluate the probability of survive at every, time. its application at different times permits a better evaluation of haemodinamically instable patient trend. introduction: the feasibility to assess pulmonary capillary pressure (pcap) offers the opportunity to determine the longitudinal distribution of pulmonary vascular resistance (pvr). the purpose of this study was to measure pcap and to calculate pvr to determine whether relevant shifts in the distribution of pvr could be expected after routine cardiac surgery. methods: the study population consisted of consecutively admitted patients after cardiac surgery. surgical procedures included coronary artery bypass graft (cabg) (n= ) and mitral valve replacement (mvr) (n=t ). pcap was estimated by analysis of the pressure decay tracing after pulmonary artery occlusion. after estimation of pcap precapillary (ra) and postcapillary resistance (rv) was calculated. a complete set of hemodynamic variables was obtained at hour and at hours after operation. results: there were no significant hemodynamic changes during the first hours after surgery. the mvr group maintained pulmonary hypertension and higher levels of pcap. ra/rv, reflecting the longitudinal distribution of resistances, remained unchanged. however, rv predominated ra during the postoperative period in both groups. objectives: evaluation of the influence of long-term continuous i.v. administration of the ace-inhibitor enalaprilat on regulators of circulatory homeostasis. methods: t trauma and sepsis patients randomly received either . mg/h (group i, n= ) or . mg/h (group , n= ) of enalaprilat i.v. or saline solution (control, n= ) as placebo for days. plasma levels of endothelin- (et), atrial natriuretic peptide (anp), renin, vasopressin, angiotensin-ii, and catecholamines were measured before injection of enalaprilat (='baseline' values) and during the next days. results: except for et, plasma levels of all vasoactive substances exceeded normal range at baseline. angiotensin-ii significantly decreased during enalaprilat infusion ( . mg/h: from . • to . • pg/ml; . mg/h: . • to . • whereas it remained significantly elevated in the untreated control patients. vasopressin increased only in the control group (p< . ) and decreased after . mg/h of enalaprilat. et remained almostunchanged in group , whereas et increased significantly in the control patients (from . • to .t• on the th day). catecholamine plasma levels (epinephrine, norepinephrine) markedly increased in the control group (p< . ), but they did not change significantly throughout the study period in both enalaprilat groups. conclusions: continuous i.v. administration of the angiotensin-converting enzyme inhibitor enalaprilat beneficially influenced systemic and local vasoactive regulators of the circulation, which are normally increased in the critically ill. thus patients at risk of (micro-) circulatory abnormalities may profit from enalaprilat infusion. objectives: to determine the time taken for hemodynamic and gas exchange variables to a reach stady-state after a change from supine to trendelenburg position (trp). methods: we prospectively studied adult patients with severe sepsis or septic shock requiring hemodynamic monitoring. usual cardiorespiratory parameters were measured at baseline, min after the patient was placed in a trp and again min after the return to a supine position. a fiberoptic pulmonary artery catheter (svo~ oximetrix, abbott) allowing continuous svo monitoring wa~used. during the protocol we also continuously measured sao~ by pulse oximetry and vco~ and vo by monitoring partial concentration of o and co ir~ inspiratory and expiratory gases (deltatrac metabolic monitor, datex). therefore, we were able to monitor cardiac output variations by dividing vo~ with arteriovenous difference according to the fick equation (co-fick). results: no significant difference in hemodynamic status was observed min after the patients were placed in trp. despite the fact that no significant change was observed in co and vo~ estimated by thermodilution, co-fick had a tendency to dedrease continuously in trp and then to return to its initial value when patients regained supine position. respiratory gas analysis showed a small but persistent continuous increase in vco without a similar trend in vo values. conclusions: we conclude that no significant hemodynamic effect was detected in our patients after min in trp. evaluation of vo from respiratory gases analysis after a change in body's position should be interpreted with caution, since the patient may not yet have reached a stady-state after rain. since vo did not change, vco~ increase was probably due to position related changes in-pulmonary gas exchange and not to a change in patient's metabolic status. objectives: to determine whether changes in svo and/or other hemodynamic parameters during weaning trials could be used to predict successful weaning. methods: we prospectively studied adult patients with a history or clinical evidence of cardiovascular dysfunction, who were unable to tolerate spontaneous breathing (sb) for hours. for all these patients right heart catheterisation was considered necessary in order to detect hemodynamic alterations during weaning. a fiberoptic pulmonary artery catheter (svo ximetrix, abbott) allowing continuous svo monitoring was sod. hemodynamic status was evaluated ~t baseline and after one hour of spontaneous breathing through a t-piece. patients were assigned to one of two groups depending on whether they tolerated sb for hours. data were analysed by analysis of variance and unpaired student's t-test we also used multiple linear regression analysis to determine which hemodynamic variables were correlated with the magnitude of svo~ change and multiple discriminant analysis to determine if asy of the above variables were associated with toleration of sb for hours and/or successful weaning (s-w). (j physiol ; ." - ) . we tested the hypothesis that the ventilatory stimulation by dead space (vd) loading and % co inhalation is accompanied by a proportionate cardiovascular change. methods: six healthy subjects, mean age, year, performed three incremental exercise tests in a randomized order: ) inspiring air without vd (air control, ac); ) inspiring air with vd of ml (avd); ) inspiring % co ; % oxygen, balance nitrogen. the ventilatory responses were examined at matched heart rate (hr) equivalent to % peak hr. results: ventilation (vi) was significantly greater (p< . ) during the avd and co tests than during the ac test at the same work rates. end-tidal co (petco ) and estimated arterial co (paco ) were significantly greater (p< . ) at w and w. oxygen saturation was significantly lower (p< . ) during the avd test than during the ac and % co exerdse. at matched hrequivalent to % peak hr, vi was significantly greater (p< . ) during the avd and % co tests than during the ac exerdse ( l, l, and /). conclusion: we conclude that the increase in xri and petco due to vd loading and % co inhalation is not associated with an acceleration in hr. sup.ported by mrc (canada). objeetlve: the production of large amounts of oxygen radicals from the onset of ~en may be responsible, st least in part, for peroxidative damage to myocardial tissue. the aim of this study was to evaluate the time dependence of plasma tbars in patients with am] receiving thrombolytie therapy (tt). patients and m~hods: filiy eight patients admitted in icu ( men and women; mean age . - . years) rec~ving systemic tt for possible am] were ~died. all patients received recorabinant haman tissue-type plasminogen activator (r-tpa). the mean time fi'om the onset of symptoms and the be~nning of tt was . - . hours. peripheral veao~s blood samples were obtained fi'om each patient before and serially after tt ( , , and hours). tbars levels woe determined by using a spectrophotometrie technique. rq~r fusion was identified by the timing of ereatine phosphate kkmse (cpk) peak (< hours). table i list the variation of plasma eoneenlrations of tbars (mean -sd) in groups (a,b, and c) as a function of time from the beginning of tr. co,arisen oftbe time cuncentzatiens reveal a difference p<o. between group ami (a and b) versus group c. the between-groups (a-c) comparison showed significant differences (p<~). ) at , and hours fi-om de begin~g of'it. comparison ofthe , and hours eonocnlratiens did not reveafl any difference becween n~ (group b) and angor (group c). condmien: we have observed a maintenance of high level of tbars in reperfused patients enly. these results suggest that the increase of tbars levels may be due to phospholipid derangament of reperfused myocytes. objective: to detemline if tbars levels may be an early index reflecting peroxidative damage in ami patients. patients and methods: by using a spectrophotometric teclmiqtm, based on a modificatien oftbe buege and aust method, tbars levels ware determined in healthy subjects (group i) , patients with several risk factors of ischaemic cardiopathy (group if) and icu patients with possible aim ( were confirmed ami (group ma) and were angor (group iiib)). peripheral blood was obtained at the time of the icu admission in the group i . electrecardiographic data and eehocardiographic wall motion were used to identify ami location (anterior, inferoposterinr and indeterminate). statistical analysis was made with a standard statistical package (rsigma, horus hardware). , h , s, , h statistically significative increase of ' ix~e/ea.ee x~* tbars levels (p< . ) only in pstients with con/tuned ami (group ilia) . no differences were found between the rest of the groups. the figure shows the relationship between the tbars values and the time from the onset of the aim's symptoms. conclusion: we have found that in am/patients the tbars levels can be used as an early index reflecting peroxidative damage occurring to ischemie tissues. perioperative risk in patients with ischemic heart disease. the protective role of diltiazem. lg. hatziantoniou, p. tassiopoulos, c. fakiolas, ! g. foussas~ m. lycourinas perioperatlve morbidity and mortality are mainly of cardiac origin, particularly among elderly patients (pts) ~ith ischemic heart disease. we performed a randomized trial, in order to investigate the possible protective activity of diltiazem (d). methods: pts (aged zo• with a history of coronary insufficiency were subjected to major urological operations. they were randomized to two groups: group i ( pts) -p:ithout d and group ii ( pts) -d ~as administered . mg/kg iv bolus hours prior to anesthesia and . mg/kg/h upon the end of operation and for at least hours post-operatively. iv was substituted by oval administration of x mg starting the next day and for the rest of hospital stay. all pts underwent daily clinical, electrocardiographic and laboratory (ck-mb) control. results: are shown in the following interactions between the heart-lung unit and a cardiac assist device are the crucial issues for successful outcome of patients under mechanical circulatory support. several factors have been indicated and we can diffrentiate between anatomical and hemodynamic interactions. especially right heart failure and pulmonary hypertension have been proven to limit left ventricutar assist device (lvad) performance. in order to study the effects of right heart failure (rhf) and pulmonary hypertension (pht) on mechanical circulatory support, we designed an experimental study in dogs and combined in six groups left heart failure (lhf) and rhf and pht, respectively. in the control group we induced lhf with subsequent occlusions of lad and cx followed by reperfusion: in the next group we supported with an lvad during minutes starting minutes after cx occlusion (group if). in the next group we added right ventricular ischemia by occluding the rca simultaneously to the cx (group iii). these both groups we repeated only with pre-existing acute pht induced by the injection of o fm glass beads (groups vi and v). a last group was similar to group v (lhf and rhf and pht), but instead of a lvad, we used bvad support. in i and v no animal survived the second perfusion period ( hours). in ii and iii (no pht), all dogs survived in stable conditions. in iv (lvf, pht), % survived, the remainder died of incomplete recovery. in vi with bvad, only % survived. in iii and v, during occlusion of the rca, the right ventricle stopped contracting and right atrial pressure and mean pulmonary pressure equalized. this lead to a significant drop in inflow on the left heart side, which still provided sufficient lvad performance in case of absent pht (iii) and lead to death due to "low lvad output" syndrome in v. this "low lvad output" snydrome could be partly overcome by bvad support. we conclude that heart-lung interactions play a major role in lvad performance. by optimizing the perioperative management, they all can be overcome, except the occurrence of alveolar leakage syndrome. obiectives : we propose a new approach of transmural pulmtmary artery occlusion pressure (paoptm), in presence ef peep, from the folluwing hypothesis : if respiratory swings of paop are compared to those of alveolar pressure (apalv = plateau pressure -total peep), an index of transmission of airway pressures to pulmonary vessels is obtained (i t = apaop/apalv). the value of the product of it by peep can be substracted from end-expiratery paop (paopee) to obtain a calculated paoptm (paoptrnc). thus paoftmc = paopee -(apaop/apalv x peep). methods : we tested this hypothesis in patients by comparing paopee, paoptmc, and paopnadir obtained within the first seconds after disconnection from the ventilator, value of reference of paoptm in absence of intrinsic peep (peepi). at zeep, peepi was absent in patients (group a) but present in others (group b). patients were studied under the peep level chosen by the attending physician-(gr a : +_ ; gr b : _+ cmh ). results : l. gr a : paopee ( _+ mmhg) differed (p < - ) from paopnadir ( • mmhg) and paoptmc ( _+ mrahg). gr b : paopee, paopnadir, paoptmc differed between themselves ( " - , + , + mmhg respectively). . good correlatkm (r - (i. ) and agreement between paopnadir and paoptm were found in gr a, while there was no agreement in gr b (bland and altman analysis). . lung compliance (v t/bpah,) correlated well with i t in both groups (r - . ), suggesting that our hypt)thesis was strtmg even in patients with peepi. conclusions : paoptm under peep ventilation can be obtained, even in patients with peepi, from parameters easily measured at the bedside. introduction: cardiopulmonary bypass (cpb) may cause ischemia in several organ systems like the heart, brain and kidneys. reactive oxygen species (ros) are formed by subsequent reperfusion and stimulation of neutrophils by cpb. ros are harmful to biological systems e.g. cellular membranes, enzymes~ dna. many natural antioxidant systems protect against the effect of ros. in patients undergoing cabg we evaluated the production of ros by total plasma antioxidant status (tas) and lipid peroxidation measured by lipofuscin flip). methods: tas (randox, uk) and concentrations ofllp (tsuchida et al.) were measured in consecutive patients undergoing cabg. all the patients had a normal serum creatinine clearance (> ml/min). serum samples were obtained a) before operation, b) after removal of the aortic crossclamp, c) at admission to the icu, d) hours after operation, e) hours after operation. results: tas was significantly decreased after removal of the aortic crosselamp ( b, c and d lower than a), followed by a subsequent significant increase of lip ( c and d higher than b). the levels of tas and lip returned to baseline hours after operation. methods: patients with preoperative lvef< % undergoing coronary artery bypass grafting were studied. after surgery, a f femoral artery catheter was inserted and connoted to a fiberoptic monitoring system (cold z- t; pulsion medizintechnik, germany); this allows, with a double-indicator dilution technique, the calculation of cardiac index (ci,l/min/m ), intrathoracic bood volume (itbv,ml/m ), pulmonary blood volume (pbv,ml/m ) and extravascular lung water (evlw,ml/kg). with a f pulmonary artery catheter, wedge (w,nunhg) and central venous pressure (cvp,mmhg) were measured, while extraction ratio (o exr,%) and oxygen delivery (do ,ml/min/m ) was calculed. peak inspiratory pressure (pawp,cmh ) and mean airway pressure (mawp,cmh ) were measured with a varflex flow transducer (bicore,sensormedics,us). the patients were studied after minutes (to) of volume controlled standard ratio ventilation (vc), and after minutes (ti) of stabilisation period of pcirv ( % inspiratory time, % pause). vt,ve and total peep were held constant in every mode of ventilation. +_ . " *'p < , versus to conclusions: these data show that pcirv : is a safe ventilatory support also in cardiac patients with impaired ventricular function, and monitoring of itbv is more reliable to measure and optimise circulatory volume status, than w and cvp. c.ledeki-,g.rldisis,s.karotzai,c.micheilidis,m.agioutantb, g.beltapaulos. objeolivee:to evaluate the influence of lvswl on the well known correlation of sr and svo . paw eight patients ( melee end females) were included in this study regerdlen of the icu ~h"niseion couse. all paints were ,'~theta~ with e fiboroptir pulmonary artery catheter connected with an oxymetfir (r)~ so /co abbot computer.for any pulmonary artery catheter insertion, two pain= of sr and svo were obtained, one dudng inserlion and one during taking the catheter out. for any pair obtained, we eleo collected the deta concemig with the pedient's hemodynamir and oxygenation end we calculated the lvswi. were significantly (p<o. ) higher in group i. conclusion: breathing room air, the less hypoxemic patients had a rather satidactory do and tissue oxygenation (pro ) because they had properly adapted their ci. the absence of this mechanism (right heart impairement ?) in the hypoxemic patients, in spite of higher blood ne and e, was responsible for the poor do and pro . objectives: acute massive pulmonary embolism (pe) increases pulmonary artery pressure (pap) and dght ventdcular aftedoad, which may lead to dght ventdcular failure. inhaled nitdc oxide (no) selectively dilates pulmonary vessels. thus, inhaled no may be of potential therapeutic value in the management of the acute phase of pe. methods: following institutional approval, ten piglets (body weight + kg) were anaesthetised (midazolam/piritramide) and ventilated using a modified servo ventilator (siemens elema, sweden; fio . ). the following variables were obtained: systolic pap (spap), mean pap (mpap), diastolic pap (dpap), mean artedal pressure (map), central venous pressure (cvp), pulmonary capillary wedge pressure (pcwp), cardiac output (co), and artedal (pao ) and mixed venous (pvo ) oxygen saturation. pulmonary vascular resistance (pvr) was calculated. to induce pe, pm microspheres (sephadex g coarse, pharmacia biotech, freiburg, germany) were injected in an amount sufficient to increase mpap to mmhg initially. rain after embolisation when haemodynamics were in a steady state (control ), inhaled no was administered. further measurements were taken min after ppm no (no ), min after ppm no (no ), and min after discontinuation of no administration (control ). the administration of inhaled no resulted in a significant decrease in spap, mpap, and pvr. the cessation of no inhalation led to a complete return to pretreatment control values (table) . co, map, cvp, pcwp, pao?, and pv~ remained unchan no administration. objectivss:evsluate the yield of recombinant tissue plasminogen activater(rt-pa, actiiyse ~ oehringer ingelheim) as a thrombolytic agent ie pulmonary embolism ie .kr~auma patients. methods: in five patients with diagnosed pulmonary embolism(blood gases, chest x-ray, echocardiography, perlesion lung scans) were given rag of actij.yse as ~ hrs infusion, followed by heparin~single j. ihjaction snd iefusion ie doses - j./kg/day).the effectiveness of rt-pg thrembo].ytic sctier~ was svaluated im . . hrs(blood gases) amd on the third dayafter t~eat-,ment(~chocardiography and lung scan). results: three hrs after actilyse was given we observed significant clinical imprevemeet,confirmed by elevation of pao and sao in dlood.echocardiegr~m on the third day showed regression of pulmonary hypertension and lung scans showed % improvement in total lung perfusien. except slight bleeding from the site of injection nc~ more thromboiytic complicatioos were observed. conclusiens: actilyse used in five hrauma patients with pulmonary embol.ism was a very effsctive and safe thrombolytic agerlt, inducing rapid and evident clinical improvement. intermittent positive pressure ventilation ( ppv) by increasing pleural pressure, decreases the pressure gradients for systemic venous return and left ventricular (lv) ejection. we have previously shown that when inspiration is synchronized with systole using synchfjv in patients with severe cardiomyopathy, that cardiac output (co) was increased relative to both ippv and non-synchronized hfjv ( ). however, it is not known if similar effects could be realized in ventilatordependent patients with lesser degrees of lv dysfunction and fluid overload. we thus compared synci-ifjv to ippv in stable patients following coronary artery bypas grafting. methods: normothermic who were stable (< % variance/h.) were studied following admission to the sicu. heart rate (hr), mean arterial (pa), pulmonary artery occlusion pressure(ppao), co by continuous thermodilutiun (vigilance, baxter, usa), mixed venous saturation (svoz) and arterial blood gases (abg) were measured after rain. of each step. ippv was simv adjusted for a rate, tidal volume and fit to insure both normal abg and a peak airway pressure < cm h,o. syncfifjv was delivered by a hfjv ventilator (acutronic) during systole with ventilator parameters adjusted to optimize abg. protocol: patients received three ippv runs (ippvi. , ) with synchfjv runs interposed (hfjvz ). statistics: anova for repeat measures and paired t-test were used to compareruns and demonstrate variability. results:no significant difference in any of the measured hemodynamic variables were seen among the ippv and synchfjv runs (table) . post hoc separation of patients by preoperative ejection fraction (ef; ef > % ; n= and < %; n= ) did not alter these results. back~ound: in man, vascular endothelium-bound ace is expressed in concentrations greater than x that in serum and is believed to be the site of synthesis of circulating angioteusin il it is unclear whether ace inlubitors interact similarly with ace in different vascular beds. coronary vessels possess all the components of the renin-angiotensin system, including ace which may be involved in normalcardiac homeostasis, as well as in the pathogenesis of various cardiomyopathies. obiecfive: to develop a method for assaying the interaction of ace inkibitors with coronary endothelium-bunnd ace in man, methods: ace a~aty was meas~ed in five patients undergoing cabg surgery, from the transeuronary hydrolysis of the synthetic ace substrate h-bpap. trace mnou~ of ~fi-bpap ( gci) were injec~d as a bolus in the root of the aorta and simultaneously blood was withdrawn from a coronary sinus catheter into a syringe containing protease inhibitors which prevented the convession of umeaet~ ai-i-bpap by blood ace. the sample was later centrifuged to separate cells from plasma and the radioactivities due to formed product (~rl-bphe) and total sh were astimated in a [b-counter. two additional such determinations of ace activity were perform~ the second in the presence of . pg/kg e (coinjected with ~-i-bpap) and the third ten minutes after e. results: all subjects were hemodynamically stable throughout the course of the there were no noticeable hemodynamic effects of e. control transcorunary metabolism of~-bpap averaged g -a: %, in agreement with previously reported data. in the presence of e, % metabolism of ~-bpap was reduced to • reflecting a • inhibition of normal ace activity. ten minutes after e, ~ri-bfap metabolism had partially recovered to :l: %, representing a -a: % inhibition of control ace activity. from this data, the dissociation constant of e for coronary ace in vivo was estimated as . x " sec "l. conclusions: we have demonstrated the feasibility of repeated, reproducible measures of coronary endothelium-bound ace activity and of its inhibition by e. this procedure is safe and can be used to study the role of ace in normal cardiac function and in card pathologies. objectives. primary pulmonary hypertension (pph) is a progressive fatal disease of unlmown origin, with median life expectancy of less than three years after diagnosis. the responsiveness of pulmonary hypertension to a variety of vasodilator agents led to the speculation that, concomitant with vascular renmdelling processes, persistent vasoconstriction is an important feature of the disease. long term use of ca-channel blockers and intravenous pgiz may improve mortality in certain populations of pph patients, but both of these treatments lack selectivity for tire lung vasculature. the aim of this study was to test the efficacy of aerosolised prostacyclin and its stable analogue, [loprost for selective pulmonary vasodilatation in pph. methods: in three patients with pph, we compared aerosolisation of prostaglandin iz (pgi ) and iloprost to a battery of vasodilatory agents (diltiazem, nifedipin, inhaled nitric oxide, intravenous pgiz). results: nebulisation of pgi and iloprost tumed out to be most favourable for achieving effective and selective pulmonary vasodilatation. pulmonary vascular resistance decreased from + to -+ dyn*s*cm (p< . ) and pulmonary artery pressure from . + . to + . mmhg (p < . ), cardiac output increased from . + . to . _+ . i/rain (p < . ), mixed venous oxygen saturation from . _+ . to . + . % (p < . ) and arterial oxygen saturation from . + . to . _+ . % (mean _+ sem of trials in patients). -month iloprost nebulisation in one patient ( gg/day in six aerosol doses) demonstrated sustained efficacy of the vasodilator r~men. conclusion: aerosolation of pgi or its stable analogue may offer as new strategy for selective pulmonary vasodilatation in pph. endothelial adhesion molecules may play an important role in the pathogenesis of myocardial cell damage, and may contribute to the progression of heart failure. we measured the plasma soluble intercellular adhesion molecule- (sicam- ), vascular cell adhesion molecule- (svcam- ), and e-selecfin (selam- ) levels in patients with acute myocardial infarction admitted within hours after onset. peripheral venous plasma-samples were collected at the time of admission, , , , , and hours after onset. plasma soluble adhesion molecule concentrations were determined by elisa. patients were divided into groups as follows: group ; killip's class (k) and without thrombolytie therapy, group ; k and with thrombolytic therapy and group ; k and . both plasma sicam- and svcam- concentrations in group and were elevated rapidly and significantly and maintained at a high level during the first days. plasma selam- level did not change in any of the groups. these results suggest that the adhesion molecules icam- and vcam- may play a role in the pathogenesis of myocardial reperfusion injury and may indicate its severity in myocardial infarction. objectives: nitric oxide (no) is known to exert cytotoxic and negative inotropic effects on cardiomyocytes. no synthase activity has been reported to be increased in infarcted area in animal model of myocardial infarction. these findings suggest that no may be an important regulator for myocardial damage and cardiac function after myocardial infarction. we measured plasma no no -(nox) levels and estimated serial changes in acute phase of myocardial infarction. methods: subjects were patients admitted within hours after onset. venous blood samples were collected at -hour intervals on the first day, -bour intervals on the nd day and -hour intervals on the rd day and th days after onset. plasma nox concentrations were determined by griess method. results: the time course of the plasma nox levels (mea~+sem) displayed a tendency to gradually increase and to make a biphasic pattern with two peaks about hours and - days after onset (basal level; . _+ . , first peak; . !-_ . , second peak; . + . ram/l). plasma nox concentration was not influenced by the thrombolytic therapy, and nox values at the time of hours after onset were significantly correlated with maximal plasma creatine kinase level (r= . , p< . ). the levels of plasma nox in the early stage of myocardial infarction (from admission to the th day after onset) did not correlate significantly with the hemodynamic parameters (left ventricular ejection fraction, pulmonary capillary wedge pressure). conclusion: the early and late increase in no production after myocardial infarction may be implicated in the deterioration of myocardial contractility and induction of myocardial damage in the early phase of myocardial infarction. range - ) fullfilling the high risk criteria of shoemaker (colectomy , gastrectomy , pancreaticoduodenectomy , others ). patients were admitted to the icu preoperatively. arterial and pulmonary artery catheters were inserted and hemodynamics and oxygen transport were measured at admission and after stabilization to predetermined physiological end points. patients were considered stable when ci > . l/min/m , pcwp > mmhg, hb > g/l, sat >. . objectives: evaluate the acute effects of , mg ipratropium bromide and , mg fenoterol (ibf) inhaled dose on pulmonary function in nonsmocers (nb:m) and smocers (s) with sever (new york heart association class ii-iii), stabile congestive heart failure(chf) and healthy subjects. methods: pulmonary function tests were performed < h postprandial. the tests consisted el arterial blood gas aspiration followed by routine spirometry and pletismography, and single-breath gas analysis. after performance of these maneuvers, the patients was administred puffs-ipratropium bromide ( , rag) and fenoterol ( , rag). for , h, spirometry was repeated. results: in resting, pulmonary abnormalities observer in the s group were more severe then abnormalities observere in the nsm group. after treatment with ibf the improvement in pulmonary function was even more marked in patients who had smoked. the mean changes by forced expiratory volume in second(eevt) was , % (p< , t) improvement and , % (p< ,ob), forced expiratory flow betwen % and % of the forced vital capacity (fef . ) was , % (p< , ) and , % (p< , ) and maxamal voluntary ventilation (mw) was , % (p< , ) and , % (p<o, ) improvement. the mean changes in normal subjects were mild (fev increased by , %,fef - by , % and mvv by , %). we observed no adverse heamodinamie conseevence and no arrthytmogenicity. conclusion." in patients with chf the airway response to ibf is highly significant. further study is needed to determine whether therapy with ibf will load to improvement quality of life in patients with chf with dearly documented venti/atory defects. compared with unilateral ima grafts, usage of bilateral ima grafts in cabg patients causes greater thoracic trauma and further reduces blood supply to the sternum and intercostal muscles. these effects may be associated with increased postoperative respiratory complications obiectives: to study the effects of bilateral ima grafts on postoperative respiratory morbidity in cabg patients. methods: two groups of patients undergoing cabg were prospectively studied: group (n= ) received both imas as grafts and group (n= ) received only the left ima. the two groups were matched for age, smoking habits, total number of grafts and preoperative ejection fraction. pao /fio ratio was measured in all patients in the icu, at , , minutes on mechanical ventilation (mv), at , , minutes after extubation (ex) and on postoperative day (pod) . in addition, radiografic scores of atelectasis and pleural effusion were assessed postoperatively. results: group had significantly longer bypass ( _+ vs + . p< , ) and aortic cross clamp time ( +- vs + , p= , ). pao /fi ratio was significantly higher in group only at minutes after extubation (table) . there was no difference in the incidence or severity of atelectasis or pleural effusion between the two groups. the duration of mv was longer in group ( +_ vs _+ , p= , ), but the length of icu stay and hospitalization were similar. there was one case of pneumothorax in group and one case of pulmonary infection in each group. after extubation m[n min min min* rain min pod ' _+ _+ + -+ - -+ _+ _+ _+ _+ -+ _+ _+ -+ mean_+sd, *p=o, o conclusions: compared with unilateral ima grafts, the usage of bilateral ima grafts in cabg patients is not associated with increased postoperative respiratory morbidity. the diagnosis of rv ischaemia is difficult in the critical care setting. the purpose of this study was to determine the ability of rv endomyocardial and interstitial ph electrodes to detect rv ischaemia in an animal model of rv infarction produced by fight coronary artery ligation. we hypothesized that changes in transmural and interstitial ph would accompany the induced tissue hypoperfusion. rv interstitial (phint) and transmural endomyocardial ph (phendo) were measured in adult anaesthetized pigs before and serially after coronary ligation. phendo and phint fell progressively and significantly following coronary occlusion. this was accompanied by ischaemic ekg changes. the absolute and relative rates of change were greater for phendo compared to phint, particularly after minutes of ischaemia, ph was unchanged in control experiments when the electrode was placed within the fight atrial or ventricular chambers, as well as when coronary ligation was not performed. these data suggest that rv myocardial ph measurements reflect coronary ligation induced rv ischaemia, ph recorded from an electrode placed against the rv endomyocardial wall via a central vein was as useful as an interstitial measurement that required a thoracotomy. this newly described technique may be helpful in clinical settings where differentiation between ischaemic and nonisehaemic causes of rv dysfunction is important. centre. depts of cardiac surgery and anesthesiology, university of bari, italy. lung injury secondary to cardiopulmonary bypass (cpb) is well recognized. nevertheless, mechanical respiratory changes after cpb have been poorly investigated. aim of the study was to evaluate the effects of cpb on respiratory mechanics. elastance of the lung (est l), chest wall (est cw), and total respiratory system (est rs) were measured in patients without previous pulmonary disease undergoing elective cardiac surgery. there were males and females; no pleurotomy was done. cpb was carried out with membrane oxygenator. mean cpb and cross clamping times were _. and • min. flow (pneumothacograph), airway opening and esophageal pressures (pressure transducers and esophageal balloon) were measured on patients sedated and paralysed. measurements were obtained before sternotomy, at the end of cpb after chest closure, four and seven hours later. est rs, est l and est cw, were measured by occluding the airways and the end of a tidal breath. before end cpb- h after h after stemotomy closed chest cpb cpb estrs (cmh /l) . + . . - . " . _+ . * . - . * est cw " . _+ . . • . + . . -+ . est l " . -- . . - . " . -_ . " . _+ . " x + sd. * p < . : anova vs "before sternotomy". our data show that cpb induces increase in est l, whereas est cw remains unchanged despite sternotomy. impairment in est l after cpb evolves within the first hours and stabilizes hours later. during the clinical course of human imunodeficiency virus infection (hiv), patients (lots) can develop congestive and dilated cardiomyopathy syndrome (dcm). the aim of our study was to analyze the prevalence of dcm among an hiv population, its clinical and echocardiographic changes under a long term follow-up and therapy with an ace-inhibitor agent (captopril). we prospectively studied pts, % ( / ) developed dcm during the follow-up study. among this group % ( / pts) were in class i and ii and % ( / pts) in class iii and iv of the nyha classification. we divided this population in a acei+ ( pts) and acei-( pts), according to the administration of captopril. we analyzed the following parameters: age, gender, race, ivda, type of hiv, cdc classification, number of t and t type cell population and its t /t ratio, therapeutic with acei, type and number of opportunist infections, mycobacteriosis and neoplasm's. we analyzed several echocardiographic parameters, which included the initial (i), final (f) and variation (a) of the lv internal diastolic (lvdd/mm) and systolic (lvsdimm) diameters, lv % of fractional shortening (lv%fs/%), ivs and posterior wall thickness and lv mass (lvm/g). the two groups differed significantly in the following parameters: left ventricular functional indices of patients (pts) with iscjhemic dilated cardiomyopathy (idcm) have a critical value in terms of clinical prognosis of this disease. three-dimensional echocardiography ( -de) is a recently developed method that gives a better evaluation of lv morphology and function. the purpose of our prospective study was to assess the clinical applicability of this new -de method in a population with ischemic dcm diagnosis and calculate its lv indices of global and regional function. we studied a group of idcm pts, mean age _+ yrs, % male gender, using a combined -de tee approach. all pts were in class ill/iv of the nyha classification. first, ekg gated images were acquired through a mechanical pullback of the tee probe, and each set of data was transferred to a conventional ibm-pc system using a dedicated -de software. computer processing and analysis of the tee images led to a -de reconstruction matrix and off-line calculation of several lv global and regional indices. in all idcm lots the lv cavity was clearly reconstructed and end-systole and diastole in several orthogonat projections, out in multiple planes and its function quantitated using -de derived indices. mean values of -de lvesv= -+ ml, lvedv= _+ ml, lvstv= _+ ml and lvef= -+ % were obtained. for all these -de parameters, good correlations were observed with -de lv measurements obtained through biplane tee analysis of the lv cavity (r>. ; p<. ) as well as regional analysis of sequential -de cut planes. conclusion: in our group of patients with the diagnosis of ischemic dilated cardiomyopathy, this new -de method could be applied. our results show that this method allows a better assessment of the lv morphology and spatial geometry, with the calculation of global and regional indices with critical clinical and prognostic value in this particular cardiovascular pathology. simultaneous left atrial (la) and left ventricle (lv) inflow analysis assessed by pulsed doppler tee illustrate the loading conditions and reflect the hemodynamics of the left heart. we performed a prospective tee pulsed doppler study with recordings of the transmitral lv filling and pulmonary venous (pv) flow drainage in a group of patients with dilated cardiomyopathy (dcm). a group of dcm patients, mean age _+ yrs, % male were studied. this population was divided according to tee severe lv dysfunction (group slvd+ % pts; group slvd- % pts) in each pt we measured the peak velocities (vel/m/sec) and time velocity integrals (vti/m) of the transmitral early (e) and late (a) filing waves, the vel and vti of the pv systolic (s), diastolic (d) and atrial contraction (c) reversal flows. -de tee evaluation of the lved, lves, lvst volumes and lvef were obtained. we calculated other parameters, such as e/a, s/d and a/c ratios and the sum of c+a vel, that refelect la systolic function and lv compliance. + -_ . simultaneous and quantitative analytical approach of the pulmonary venous and transmitral flows and ventricular volumes improve the non invasive assessment and understanding of left ventricular diastolic function and cardiac performance in dilated cardiomyopathy patients. objectives : to assess the hemodynamic effects of fluid loading (fl) in acute circulatory failure (acf) due to acute massive pulmonary embolism. methods : hemodynamic measurements (fast-response thermistor pulmonary artery catheter) were performed at baseline (baseline) and after a rapid fluid loading with (fl ) and (fl ) ml of dextl'an (rhemacrodex| in patients free of previous cardiopulmonary disease ( • yrs) with acf (ci < . l/rain/m ) due to angiographicalty proven mpe (miller score > ) . results : are expressed as mean _+ sem and compared by anova. a significant negative correlation (r = . ) was observed between baseline rvedv[ and the effects of fl on ci. such correlation was not observed between baseline rap and the fl induced increased in ci. conclusion : fusibmificantly increases ci in acf due to mpe. however, the simultaneous decrease of arterial content due to hemodilution, limits the benefits expected from improved ci on peripheral oxygenation. obiective: to examine the hemodynamic effects of external positive endexpiratory pressure (peep) on right ventricular (rv) function in acute respiratory failure (arf) patients. methods: incremental levels of peep ( - - - cmh ) were applied and rv hemodynamics were studied by a swan-ganz catheter with a fast response thermistor for right ventrieular ejection fraction (rvef) measurement in mechanically ventilated arf patients (lis = . ~- . sd). according to the response to peep , two groups of patients were defined: group a ( pts.) with unchanged or increased rv end diastolic volume index (rvedvi) and group b (h pts) with decreased rvedvi. results: in the whole sample cardiac index (ci) and stroke index (sj) decreased at all levels of peep, while rvedvi , rv end systolic volume index (rvesvi) and rvef remained anchange d. at zeep the hemodynamic parameters of the two groups did not differ. in group a, ci decreased at peep , rvef decreased at peep (~ . %)~ rvesvi increased only at peep (+ . %) and rvedv[ reded unchanged. in group b, ci and rvedvi started to decrease at peep , 'rvesvi decreased only at peep (- . %), anf rvef was unchanged. individual behaviors of the hemodynamic parameters at the levels& peep were studied. rvedvi and ci were significantly correlated in out of:l patients in group b, and in no patient of group a. on the contrary, mpap and rvesvi were significantly correlated in out of patients in group a, and in no patient of group b. the slope of the relationship between rvedvi and rv stroke work index (rvswi) expresses rv myocardial performance. this relationship was significant (no change in rv contractitity)in patients of group b and in patients of group a. in some patients of group a, increments of peep shifted the rvswi/rvedvi ratio rightward inthe plot (rv function decrease). conclusions: in arf patients peep causes more often a preload decrease with unclmnged rv conctraetility. on the contrary, the finding of increased rv volumes during the application of peep is related to a decrease in rv myocardial performance. thus, these data suggest that application of peep might be considered as a stress test to assess rv function. right introduction: after heart transplant (ht), the right ventricle can be subject to an acute pressure overload, especially in cases where there is a preexisting severe pulmonary hypertension. this provokes right ventricular failure and, occasionally, circulatory collapse in intensive care unit. desire the advances that have been made in systems for preserving the donor heart and in post-surgical management, we have failed in our attempts to totally avoid this problem. the right ventricular function, although it usually remains within tolerable limits in these patients during the post surgery period, represents a factor which limits the results achievable in clinical transplant programmes. objectives: to determine the maximum tolerance of the right ventricle (mxtrv) when faced with acute pressure overload. to study the function of both ventricles of the healthy heart (donor) when faced with different degrees of pulmonary hypertension. to detect possible interactions between the ventricles in the absence of the pericardium to approximate the experimental model to the clinical model of ht. materials and methods: the pulmonary artery is progressively constrained in an experimental model until biventricniar failure is detected. this experiment is performed in two diffferent situations: with and without pericardial integrity. results: when pericardial integrity is maintained the mxtrv faced with a pressure overload is . + . nun hg. when this pressure is exceeded there is a circulatory collapse with a sharp fall in the cardiac output and in the aortic pressure. however, when pericardectomy is performed (model similar to ht), only • . nun hg is tolerated (p < . ). conclusions: with the pericardium open, as in heart transplant, the maximum pressure that the right ventricle can support is significantly less than with the pericardium closed. the pericardium has a positive effect in protecting the systolic ventricular interaction. it is, therefore, advisable to close the pericardium after heart transplant. jb prrez-bernal, a ordrfiez, a. heroandez, jm borrego, map camacho, c cruz, mac s~nchez, j monterrubio, c garcia, e. gonz~lez. hospital uulversitario " virgen del rocio ". sevilla. espaiqa. introduction: nowadays cardiomyoplasty isused incases of cardiac insufficiency as an alternative to cardiac transplant. after surgery the patients show a noteable improvement with the aid of this "biological circulatory assistance". some researchers suspect that the improvement could also be due to the formation of new blood vessels from the muscle that wraps the heart, nourishing the ischemic myocardium. objectives: our cardiovascular research group has proposed as an objective, the detection of any possible myocardial neovascularization through the muscle used for cardiomyoplasty. in the case that there are new blood vessels to the diseased myocardium through the wide dorsal muscle in which it is wrapped and which aids it mechanically, it would be possible to confirm the worldng hypothesis that cardiomyoplasty not only improves the cardiocirculatory funcfinn mechanically but also by facilitating a better blood flow to the ischemic myocardium. materials and methods: the cardiomyoplasty technique is described using an experimental model of myocardial ischemia. the vascular cast is achieved by injecting methacrylate simulataneously into both the coronary tree and the wide dorsal muscle, in five experiments the connections between the coronary vascular system and the vascular structure of the wide dorsal muscle are demonstrated, conclusions: we have demonstrated that cardiomyoplasty, as well as improving ventricular function, favours the revascularization of the myocardium. cardiomyoplasty could be indicated for cases of ischemic cardiopathy in patients in whom it is not possible to perform direct revacularization using conventional methods. a the therapeutic cardiological manouevres necessary in cases of ischeima reperfusion have increased considerably: fibrinolysis, transluminal angioplasty, coronary revascnlarization surgery and cardiac transplant. the appearance of a specific pathology ht acute reperfusion has been related to free oxygen radicals (for) generated by oxidative damage. objectives: to evaluate the appearance of for during a conti-olled process of ischemia-reperfusion in an experimental biological model and compare it with that in clinical cases. materials and methods: transitory cardiac ischemia was performed in five rabbits by reversible surgical ligation of the descending anterior coronary artery. after minutes coronary reperfusion was performed. blood samples were taken in the basal situation, at the end of ischemia and at , and minutes after the start of reperfusion. malondialdehyde (mda) was measured to evaluate the degree of lipid peroxidation (oxidative damage to the membrane). in ten patients undergoing conventional cardiac surgery the production of for was measured after aortic clamping. results: we observed that after minutes of reperfusion there was a highly significant increase (p < . ) in the mda values (mean = . /zmols/l). these returned to basal levels after and minutes of reperfusion. conclusions: an "explosion" of oxygen free radicals was detected very quicldy, just a few minutes after post-ischemia reperfusion. thus, if antioxidant agents are to be used to reduce the toxic effects of the for, these will ordy have a therapeutic effect if they are administered in the early phases of reperfusion. introduction: aortic connterpulsation is a ventricular assistance widely used in intensive care units in patients with cardiogenic shock as a provisional ventricular assistance. paraaortic or external aortic counterpnlsation is been investigated as a definitive veutricular assistance in those cases of terminal congestive heart failure and when heart transplantation is counterindicated. aims: to assess the haemodynamic effects of an aortomyoplasty in a biological model of congestive heart failure. material and method: as specimens, we used "large white" pigs. mean weight was kg. after the administration of conventional anaesthesia, dissection of the ladssimns dorsi muscle was performed on the samples at the laboratory of experimental surgery of our hospital. then we performed a thoracotomy at the level of the fourth intercostal space to reach the thoracic aorta. the aorta is dissecated centimetres from the exit of the subclavia and it is wrapped by the dissecated muscle. a cardiomyostimulator is provided in order to allow the synchronization between the diastole and the muscle contraction. the model of heart failure was provoked using verapamil plus propanolol i.v.. results: a significant increase of the aortic diastolic pressures and a significant decrease of the left ventricle telediastolic pressures were observed. this improvement in the parameters (dpti/tti) implies an increase of the coronary perfusion in a model of heart failure. conclusions: using the external aortic counterpulsation, the aortomyoplasty improves the coronary perfnsion and the heart efficiency in patients with heart failure in whom no conventional therapeutic action is possible. the permanent character of the paraaortic counterpulsation is it main advantage. the appearance of specific pathologies as a resuk of myocardial reperfasion has been related to the oxidative damage secondary to the release of oxygen derived free radicals (ofr). during the myocardial ischemia induced during heart surgery with extraeorporeal circulation, severalsubproducts of the oxygen are produced that shall cause toxic effects after the reperfusion which could be counteracted by the physiological antioxidant systems and/or provided by the medication. aims: to asses the ofr during heart surgery. to check whether an antioxidant treatment administered in the preoperative period make decrease the levels of ofr before and after the myocardial reperfusion and to verify whether its administration have any beneficial effect on the intra and extraoperative management. material and method: the study comprehends patients studied as two groups of individuals each (a and b). all patients underwent conventional heart surgery of valvniar substitmion or myocardial revaseularization. group a patients were administered rag/ hours of vitamin e (tocopherol acetate) hours prior to the intervention as antioxidant treatment. group b patient were not administered vitamin e. we assessed the quantity of malondialdehido (mda) to assess the degree of lipidic peroxidation or oxidative damage of the membrane during the myocardial ischemia and nm after the reperfusion. conclusion: patients who underwent heart surgery and were treated with tecopherol acetate in the preoperative period presented levels of rlo significantly lower than those who were not administered the drug, both during the intraoperative period and after myocardial reperfusion. we detected in these patients a need for antiarrhythmicals and pharmacoiogical support with catecholaminas, although not significant, both in the introaperative period and the immediate postoperative period. recommendations for the treatment of pulmonary embolism (pe) in the presence of right atrial thrombus (at) are conflicting. because of a significantly higher mortality rate due to fulminam or recurrent pe, there is a necessity to treat patients (pts) with mobile type a thrombi compared to pts with adherent type b thrombi. therapeutic strategies include anticoagulation, thrombolysis (t) or surgical thrombembolectomy. combination thrombolysis (cot), predominantly used for the treatment of acute myocardial infarction proved to prevent reocclusion of the infarct related artery at a comparable rate of hemorrhagia. benefit has been related to the alteration of hemostatic proteins by non-fibrinspecific thrombolytic s. administration of cot in pe has been performed sporadically. in the present case, a -year old male with no history of prior cardiovascular disease developed acute dyspnea which was related to pe in the presence of deep vein thrombosis of the left femoral vein. therapeutic anticoagulation was installed for a couple of days until there were several bouts of deterioration. biplane transesophageal echocardiography (tee) was performed and revealed a large, wormlike, hypermobile thrombus within the right atrium. computer tomography (ct) of the chest detected a saddle embolus in the bifurcation of the pulmonary tmnk almost occluding the entire left pulmonary artery (pa) and parts of the right pat consisted of mg frontloaded rt-pa and the subsequent continuous administration of urokinase in a dosis of . u/hr for hrs followed by therapeutic anticoagulation. symptoms, blood gases and ecg improved steadily during infusion, no adverse effects, i.e. minor or major hemorragia were registered. follow-up ct promptly after termination of t showed almost complete resolution of the saddle embelus, whereas tee showed complete dissolution of the at. ' finally, the patient was switched to oral anticoagulants and had an uneventful clinical course until he was discharged. conclusion: in the present case, cot was effective for the treatment of a complicated pe without any adverse effect. introduction: nowadays we can assist hearts with problems of insufficiency by techniques other than transplant. many researchers believe that the best way of assisting insufficient heart muscle is with another muscle from the patient. this technique of ventficular assistance is known as cardiomyoplasty. we describe the surgical technique of cardiomyoplasty using a biological model. the transformed skeletal muscle is transferred to the thoracic cavity where it wraps the heart and assists it. the choice and preparation of this muscle is currently under investigation. our group has focussed on the development of protocols for electrical stimulation to transform a skeletal muscle into a muscle which resists fatigue and which is functionally similar to the myocardium. we detect the optimum time at which this muscle has been transformed, by studying the transmembrane action potentials using intracellular electrodes. when the action potential of the trained muscle behaves like cardiac muscle we consider it ready for cardiomyoplasty. conclusions: cardiomyoplasty is an alternative surgical technique to cardiac transplant, which has a great future in the treatment of patients with advanced cardiac insufficiency. we describe methodology which, by intracellular techniques, allows selection of the optimum moment of transformation of a skeletal muscle trained to perform,like cardiac muscle, without suffering fatigue. purulent pericarditis is a rare disease. its treatment associate systemic antibiotics and drainage of the pericardium. we report a ease of purulent constrictive pericarditis in which intraperieardial fibrinolysis was use. a years old patient admitted in our icu for a constrictive pericarditis as a complication of a purulent pericarditis diagnosed seventeen days before. he had also an aehalasia and the o'esogastric endoscopy had found an oesophageal neoplasm. a fistula was not seen, indeed pericardial of flora was the same that oropharyngeal. hemodynamie and echographic study had confirmed a constrictive pericarditis. because of the poor state of the patient an intraperieardial fibrinolysis was prescribed ( . ui of streptokinase on days , , , ). fluid drainage was improved and cardiac output was also improved (day : . .min "i, day : . l.min'l). no change ofhemostasis was noted. a pericardeetomy and an oesophagectomy were performed after days of evolution. eighteen months latter the patient was still alive. intraperieardial fibrinolysis seems an interesting therapeutic way if rapidly prescribed in the purulent pericarditis course. the decrease in the systolic pressure following a mechanical breath, termed ddown (delta down), has been shown to be a sensitive indicator of preload ( , ) . however, the clinical use of this method necessitates the introduction of a short apnea. we have therefore developed a respiratory systolic variation test (rsvt) which obviates the need for apnea. the test is based on the delivery of successive breaths of increasing magnitude ( , , , and ml/kg). a line of best fit is drawn between the minimal systolic values (one after each breath) and the downslope calculated as the decrease in blond pressure for each increase in airway pressure ( mmhg / cmh ). in mechanically ventilated patients the rsvt was performed during controlled mechanical ventilation under sedation. the test was repeated after the administration of ml/kg of plasma expander. the initial mean downslope of the rsvt was -. + . mmhg/cmh . following volume loading the downslope decreased to -. + . (ns). at the same time, cardiac output (co) increased by . + . l/min (p<. ), end-diastolic area (determined by tee) increased from . + . to . + . cm (ns), and paop increased from + to + mmhg ( p < . ). the preinfusion downslope value of the rsvt correlated significantly with the increase in the co (r = . ) and the eda (r = . ). methods: an expert system has been constructed running on a multimedia computer with the two objectives in mind, viz training of inexperienced staff, and protocol guidance with treatment regimes for all staff. the system is based on experience gained from two previous systems, the one for dealing with acid-base and electrolyte problems in icu patients; the second for stabilisation of patients with heart rate and blood pressure abnormalities. the training section takes the form of a stage-by-stage account of the insertion of the pac and displays of correct waveforms, coupled with indications of possible incorrect placements, and guidance when failing to achieve the perfect positioning. the treatment protocol section extends an existing protocol for correcting abnormalities in heart-rate and blood-pressure, and now takes account of all the indices as measured by the pac. the system will suggest treatment to correct such things as abnormal wedge pressures concomitant with parameter values throughout the rest of the cardiovascular system. the type of patient eg post-operative cardiothoracic or i. c. u. trauma, will be taken into account when recognising abnormal parameter values and when prescribing treatment. results: a working system which will be improved by the finetuning being carried out. the results and lessons learnt will be presented at the conference. method: septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; map < mmhg) or the requirement for a noradrenaline (na) infusion ~ . g/kg/ rain with a map --< mmhg. cardiovascular support was limited to na + dobutamine (db). c was given for up to h at a fixed dose-rate of either , . , , or mg/kg/h iv. during c infusion, na was to be reduced and if possible withdrawn, whilst maintaining map above mmhg and the cardiac index (ci) as clinically appropriate. assessments were made at baseline (t = ); at i h from the start of treatment (t - ); and at the end of treatment (t - ) with c . conclusions: c does not appear to increase mpap or worsen pulmonary gas exchange in patients with septic shock, when given by infusion for up to h. c is a novel vasoactive agent for the treatment of septic shock which will now he evaluated in a randomised, placebo-controlled safety and efficacy study. objectives : to compare cardiac output (q) data obtained for thermal indicators in pulmonary artery (qtpa) and aorta (qtao) and for the stable isotope hzo in aorta (q v~ o) with indocyanine green (icg) in aorta (qicg) as reference. methods : an indicator solution of ice cold h ( . ml), h ( . ml) and icg ( mg) was injected as bolus via the injection port of a swan-ganz catheter. qlco and qzmo was measured using a dual optical system (penn lab instruments, philadephia, pa, usa). qtpa and qtao was measured using a in contrast to the recoveries of thermal indicator in pa and h in aorta the :~covery of thermal indicator in aorta was significantly increased in group ii (n= boluses) over group i (n= boluses) ( . <- . vs. . +- . , p= . ). conclusions: the "overrecovery" of thermal indicator in aorta is in agreement with " biscks deconvolution study (i) and results in erroneous values for q. the most pausible explanation is the distortion of the thermal curve caused by the slow response time of the thermal detection instrument as shown by ganz ( ) objectives: to compare data obtained with the double indicator dilution method using indocyanine green (icg) and the stable isotope h for the estimation of extravascular lung water (evlw hzo) to gravimetriu lungwater data (evlwg~). methods: an indicator solution oflcg ( rag) and h ( . ml) was injected as bolus via the injection port of a swan-ganz catheter. dilution curves for icg and zh was registered in aorta with a dual optical system (penn lab instruments, philadephia, pa, usa). cardiac output and mean tranist time was measured for both tracers (qico, tlco, q n o, t o) ( ). data analysis: evlwg~av was reference for evlwzhzo calculated as q hzo times the difference in mean transit time between t nzo and rico (atm n). as reference for atzn o evlwg~,v was divided by q~cg to obtain atg~,. a reference distribution volume for h was calculated as the sum of central blood volume and evlwg=v. boluses were administrated in a group (i) of anaesthetized pulmonary healthy sheep while q was altered. another boluses were administrated in a group (ii) of anaesthetized sheep with stable oleic acid induced pulmonary oedema. evlwg~v measurement was performed postmortem. results: for boluses h parameters were not significantly different from their respective reference parameter: at vao . +_ . s vs. atg~, . + . s, evlwzh o -+ ml vs. evlwg~,~ + ml. in group i the ratio between hzo parameters and respective reference parameters (n= ) were independent of qlco from . to . l/min. obiectives: to assess the thermo dye method using indocyanine green (icg) and thermal indicator for the estimation of lung water (evlwt). methods: ice cold indicator solution of icg ( mg) in water ( ml the aim of the study was to assess left and right ventricular function in the early postoperative period after orthotopic heart transplantation to elaborate therapeutic approaches of heart function abnormalities correction. mathefial and methods. haemodynamic monitoring data of twenty one patients ( men, women ) age from to were studied. cardiac output, pulmonary artery, right atrium and pulmonary wedged pressure were measured with swan-gans catheter. central haemodynamic indices were calculated with the help of computer-based monitoring system. relations of ventricular stroke work index to it's end-diastolic pressure were used for ventficular function assessment. results. in most cases right ventricular disfunction was the main problem. isolated fight ventficular failure with high pulmonary vascular resistance (pvr) was observed in % ( pts), without high pvr-in % opts) and with left ventricular failure-in % ( pts). one of the most important reasons for fight ventricular failure was the time of heart ischemia more than min, which is of great importance in the ease of distance harvesting. the most effective treatment for cardiac failure was combination of dobutamine with i oprotherenol, atrial pacing and vasodilatators in case of right ventfieular disfunction. all cases with isolated right ventricular failure were treated sucsessfully. biventricular heart failure was a sighn of bad prognosis and the reason of death in cases. conclusion. right ventfieular disfunetion is the main problem during transplanted heart adaptation in the early postoperative period. optimal therapeutic management of cardiac disfunction includes infusion of dobutamine in combination with isoprotherenol, atrial pacing and vasodilatators. cardiology-department of clinical centre-kragujevac institution for occupational health "zastava"-kragujevac, sr yugoslavia the aim of the investigate is analisis five years survives patients with a.i.m.in dependence of locality and risk-factors. we ana~sed- ~-pat~e~ts ( males and woman), average , years. for statistic evaluation we used life-table slstem in oder to estimate prognostic determinants. patients with respkatory muscle paralysis may benefit from respiratory assistance by abdomino-diaphragmatie pneumatic belt. we used a non invasive technique, m-mode sonography, to assess the effect of this device on diaphragmatic excursion. we measured the amplitude of right diaphragm motion in seven patients with duehenne muscular dysl~ophy in supine position with various thoracic posture ( ~ ~ ~ without and during pneumatic belt respiratory assistance. without respiratory assistance, the thoracic posture had no significant consequence on the amplitude of diapttragm motion, either in quiet or deep breathing. the pneumatic belt increased the diaphragm motion amplitude from . +__ . mm to . +_ . ram (p = . ) at ~ tilt angle, and from . + . mm to . + . mm (p = . ) at " tilt angle. the tidal volume increased from + to + rut a * tilt angle, and from + to + ml at * tilt angle (p = . ). two patients could not bear the horizontal position ( ' tilt). in the five other patients, the pneumatic belt increased but not significantly the amplitude of diaphragm motion ( . + . mm to . + . ram). after an overnight respiratory assistance, pao increased from . +_. . to + . mmhg ( = . ), sao increased from . + . % to . +_. % (p = . ), and paco decreased from + . to . +_. mmhg (p = . ) according to the ventilatory pattern result, m-mode sonography allows to measure non invasively the improvement of diaphragm kinetics obtained by pneumatic belt respiratory assistance, and may be helpful for its adjustment. objective: to study the effect of flow triggering (flow sensitivity and l/min) vs pressure triggering (-lcmh ) on inspiratory effort during pressure support ventilation (psv) and assited/controlled mode (a/c) in stable copd patients non-invasively ventilated with a full face mask. methods: the patients were studied during randomized min. runs using a bird st ventilator at zero peep (zeep). trigger values for pressure (-lcmh ) and flow ( l/rain) were the lowest allowed by this ventilator. the transdiaphragmatic pressure time product per breath (ptpdi), dynamic intrinsic peep (peepi,dyn), maximal airway pressure drop during inspiration (apaw) andl ventilatory variables (ti,te,ttot,rr,vt and minute ventilation) were measured. results: no major problems due to airleaks or to auto-triggeriffg phenomena were observed in the patients, so that all of them were able to perform all the protocol runs. minute ventilation and respiratory pattern were not different using the two triggering systems. the ptpdi was significantly higher during both psv ( . + . cmh: x sec) and a/c ( . + . ) with pressure triggering, as respect to psv ( . + . , p< . ) and a/c ( . + . , p< . ) with flow triggering ( l!m). no differences were observed between and l/min flow triggers. apaw was also significantly larger during pressure triggering; peepi,dyn was reduced during flow triggering being . + . cmh (psv flow trigger) vs . + . (psv pressure trigger) and . +_ . (a/c flow trigger) vs'f~ +l (atc pressure trigger). conclusions: in stable copd patients non-invasively ventilated, flow triggering reduces the respiratory effort during both psv and aic mode as compared to pressure triggering. this may be partly due to a decrease in peepi,dyn using a flow-by system. objective. cardiac output is higher during alternating ventilation (av) (i.e. differential ventilation of the lungs with a phase shift of half a ventilatory cycle) than during synchronous ventilation (sv) of both lungs . we verified the hypothesis that the higher cardiac output depended on a lower central venous pressure and intrathoracic pressure, due to a lower mean lung volume, which we attributed to part of the expansion of the inflated lung at the expense of the expiring, opposite lung . we studied this interaction between the lungs during one-sided inflation, which we called cross-talk. method. in anaesthetized and paralyzed piglets we applied short periods ( s) of one-sided ventilation ( breaths per rain, bpm), while the other lung was open to the ambient air. the air flow into the non-ventilated lung during expiration of the ventilated lung was integrated to volume. we studied -to-r and r-to-i cross-talk at ventilatory rates of , and bpm. the amount of cross-talk was the volume displacement in the non-ventilated lung. results. during bpm the r-to-i crosstalk was _+ . % (mean +__ sd) of the tidal volume to the right lung and the -to-r crosstalk _ . % of the left tidal volume. both values increased at bpm to _ . % (p < . ) and _ . % (p < . ) respectively. the values at bpm were in between., conclusion. we concluded that the lower mean lung volume and lower thoracic expansion during av compared to sv depends on partial expansion of the inflated lung into the non-inflated lung, resulting in a lower mean intrathoracic pressure as the main reason for the higher cardiac output during av. obiective: natural surfactant given for rds in premature infants leads to a rapid improvement in oxygenation, but lung compliance did not improve in most studies. however, acute effects on lung mechanics during and immediately after surfactant administration have not been studied before. methods: a total of administrations of bovine surfactant in recommended doses was given via a small catheter into the distal endotracheal tube either as a bolus (n = ) or as a slow infusion (n = ) in infants with established rds. static compliance (c), resistance (r) and time constant (tc = cxr) of the lung were measured every minutes with a lung function cart (sensormedics ) without interrupting ventilation. infants receiving synthetic surfactant were studied as controls. results: after surfactant as a bolus or during infusion c first decreased but then increased, whereas r increased immediately with great fluctuations but did not return to baseline. this pattern was more pronounced in infusion than in bolus administration. change of c and r varied greatly in the individual case, maximum c was > %, maximum r > % of baseline value. retreatment was followed by an increase in r in all patients, but c increased only in the one who was responder. patients receiving synthetic surfactant had no change of c or r and were non-responders. ob~i ctives= acute lung injury (ali} sometimes induces severe hypoxernla which may be refractory to conventional modes of mechanical ventilation (mv). the elm of this study was to observe some cardio-pulmonary effects of an alternative method of ventilatory management of severe ali. five patients with severe ali (murray scores > ) requiring mv were studied. protocol inclusion was considered when a control-mode of mv (with a pzo~=l. and a peep level < cme=o} was not able to get either a p.ojf=o= ratio > or a s.o= > %. patients were sedated, paralyzed, and a ventilator (serve c) was used for pressuz'e-control ventilation (pcv). fio= was maintained at . and peep removed. continuous gas flow ( • ml/kg] was humidified and jet delivered through a tube ( ram id, ml capacity, . ml/cm h=o compllancel ended in a nozzle ( . mm is) attached to the endotracheal tube connector. a thermodilution flcw-dlrected catheter was inserted in pulmonary artery. following variables were recorded minutes before and after protocol started: tidal volume (vt), minute ventilation (vz), intratracheal pressures (p~w), wedge pulmonary artery pressure (wp), central venous pressure (cvp), mean arterial pressure (map), cardiac index (ci), arterial and mixed venous oxyhemoglobin saturation (sao=, svoa) , oxygen delivery (do~) , oxygen consumption (vo ) , intrapulmonary shunting (q./qt) , and oxygen extraction ratio (ero). this observation suggests that hfpv could allow to ventilate at lower fin and improve blood oxygenation during the acute phase after inhalation injury reducing toxicity risk related to high fin . further studies are necessary to confima these results and evaluate the possible implications on mortality alter smoke inhalation and for other icu pts. objectives: to design a system for volume controlled high frequency ventilation (hfv) and to estimate the dependence of the tidal volume (vt) on frequency (f) in normocapnic ventilation in rats at frequencies - hz. methods: a new system for volume controlled hfv was devised consisting of the generator of the constant flow during inspirium and the constant pressure during expirium. the ventilator allows ventilation at frequencies - hz with the relative inspiratory time (ti) . - . . the airway pressure was measured at the proximal port of tracheostomic cannula , at the same site inspiratory and expiratory flow was measured using modified lilly-type of pressure-differential flow sensor. non-linearity of flow sensor was compensated on line by derived equation based on calibration at static and dynamic conditions. flow and pressure data were evaluated on line using original software. value of the positive end expiratory pressure (peep) was serve-regulated by analogous feed-back. in animal experiments white wistar rats ( - g) narcotized with ketamine/xylazine with cannulated carotid and femoral arteries were kept at the rectal temperature ~ the arterial pressure was monitored. after traeheotomy the metal cannula ( mm [.d.) was inserted, animals were curarized and ventilated at the following condition: peep = . kpa, ti = . . the dead space of ventilator including canula was . ml. the initial frequency was hz and rain after each change of the ventitatory regimen the blood gases analysis was performed. the frequency was changed according to the following schedule : hz--> hz--> hz--> hz--> hz--> hz--~ hz--> hz. vt for each frequency was regulated to maintain normocapnie ventilation with arterial pco = + mm hg. the arterial po was always above mm hg. results: for normocapnie ventilation in rats the following tidal volumes vt [ ml/kg] were found : vt = . --+ . ml/kg for ft = hz, vt = . + . mukg for fz = hz, vt = . +_ . ml/kg forf = hz, vm = . + . ml/kg forf = hz andvmt= . + . mukg for fs = hz (presented as mean values _+ s.d., n = ). the regression analysis using the mean values resulted in the equation for normocapnic vt in rats in our experiments : vtn = . * f-e. . conclusions: the described system allowing ventilation in a wide frequency range - hz with accurate measurements of airway pressures and vt might be useful for optimisation of artificial ventilation in new-barns with different lung pathologies. supported by grants iga mz cr nr - and gacr nr . s intensive care unit. university. hospital of south manchester, uk. methods: measurements were conducted on ventilated patients (puritan bennett ac with metabolic monitor pb set to measure end tidal co ). all measurements were repeated with the patient stabilised at cm. cm and cm peep. inclusion criteria were: ) haemedynamic stab(l( .ty for hr; ) pulmonad" anon" flotation catheter in situ: ) volume control ventilation with plateau of . s: ) fio ~ > . to maintain pao~. > kpa with em peep: ) qs/ot > %; ) pao /fio ratio < . measured variab!es included: r minute volume: plateau ainvay pressure: applied and intrinsic peep: fractional end tidal co ; arterial and mixed venous blood gases and hacmod).ttamic variables. results: statistical analysis was performed using repeated measures anova. significant decreases in cardiac index (ch p< . ), compliance (p<t). ) and o,'gcn deliver, index (do , p< . ) occurred with increasing peep (table ) . no other variable showed any significant change. methods : all consecutive patients orally intubated in the micu between january to april were studied. etts were positioned according to the reference marks mentioned above (measurements from upper incisors). the position of the ett tip in relation to the carina was measured on the chest radiograph done with the patient's head in neutral position. results : a total of men and women were studied (n= ). the mean distance of ett tip to carina was . cm. using the reference markings, cases ( . %) had the ett tip < cm from the carina and cases ( . %) > cm. one case resulted in an endobronchial intubation. the mean height of all patients were cm ( - ) for males and cm ( - ) for females. of the patients with ett tip < cm from carina, the mean height was cm and cm respectively. ~ onclusion : adopting the above quoted reference marks did not result in ideal positioning of the ett in a significant proportion of cases ( . %). we postulate that [s because our asian population is generally shorter than those in previous studies. objectives: to measure the changes of pulmonary mechanics before and after tracheostomy in patients with prolonged mechanical ventilation and to determine factors that predict the outcome of liberation from mechanical ventilation. design: prospective. setting: respiratory intensive care unit (ricu) in a tertiary hospital. patients: twenty patients with chronic lung disease requiring long-term mechanical ventilation. tracheostomy is indicated for further care. intervention: tracheostomy. measurements and results: pulmonary mechanics including respiratory rate (rr), tidal volume (vt), peak inspiratory pressure (pip), intrinsic positive end ex~ piratory pressure (peepi), lung compliance (cld), mean airway resistance (rawm), work of breathing (wob), pressure time product (ptp) by bicore cp- pulmonary monitor were recorded hours before and after tracheotomy. ventilator setting parameters remained the same during surgical intervention and were also recorded for comparison. generally, the mechanics including pir wob, raw~x and ptp showed improvment after tracheostomy. but only pip was significantly reduced (pre . _+ . to post . _+ . , p < . ). changes of wobp showed significant correlation with pre-operation rr, minute volume (mv), wobp, and peep(. changes of raw m were also significantly correlated with pre-operation peep, vt, and raw m. the patients were divided into two groups according to their outcome after two week follow-up. group included eight patients who were completely weaned from ventilator; group included twelve patients who still remained ventilator-dependent or were mortality. there was no difference in age, duration of mechanical ventilation, pro, post or changes of several lung mechanics between the groups of patients. pre-tracheostomy peep i and cld showed significant difference between these two groups ( . _+ . vs . + . in peepi; . _+ . vs . _+ . in cld, p < . ). pre-tracheostomy ventilator setting in mode of assist/control also showed significant higher percentage in group ( % % in group vs . % in group ). conclusion: in prolonged mechanical ventilation patients with chronic lung disease, tracheostomy will significantly improve pip and slightly reduce wobp, raw m and ptr patients who used pressure support mode before tracheostomy had better underlying lung conditions (lower lung compliance and auto-peep) will have better chance to wean from mechanical ventilation. forty-eight infants with congenital diaphragmatic hernia presenting within the first hours of life, who underwent surgical rapair,were analysed prospectively in order to produce a reliable inde x of severity of disease that would reliably predict eventual outcome. there were survivors and deaths in this series (mortality %).using arterialpco values measured hours after surgical repairand correlating them with an index of mechanical ventilation,we have been able to clearly define two groups of diaphragmatic hernia based on their response to hyperventilation. the first group, with co retention and severe preductal shunting,was unresponsive to hyperventilation with high rates and pressures the mortality was %. the second group responded well to hyperventilation and demonstrated reversable ductal shunting only. survival in this group was %. arterial co accurately reflects the degree of lung development in this disease and separates those patients with severe pulmonary hypoplasia where the outcome is invariably fatal, from those with a well developed contralateral lung where there is excellent potential for survival. respiratory failure unit, dpt medicine, univ. thessaloniki, thessaloniki, greece the variability of arterial blood gases (po , pc ) and the ph (abg) was examined in stable icu patients, few hours before a successful weaning from the ventilator. all patients were lightly sedated and the ventgatory conti~ons were pressure support (ps) for and ps plus intermitted mantatory ventilation in ii. [n each patient, speciments of abg were measured at min intervals during a - study period. at the same time with abg the arterial blood pressure (bp), the heart rate (cf), the tidal volume (tv) and the respiratory rate (n r were measured. for all the patients, the mean coefficient of variation (c) was . percent for po , . percent for pco and . percent for hco . the average sd for ph was . , the corresponding c for systolic bp, diastolic bp, cf, tv, rf were . , . , . , . , . percent. we conclude that the spontaneous variability of arterial blood gases in icu patients is not substantial ~hen they have stable the heamodynamic and the ventilatory parameters. deptx?fa'aaesthesioiogy and reanimation, rhe sechenov medical academy, moscow, russia objective: ~he prevention and treatment of hypoxia in the critical patiems. methods: i~fusions of perphtoran -a blood substitute with gas-transporting fimclion based on perphtorhydrocarbon -in patients with acute hypovolemia, microcirculatory distnrbance~ tissue gas exchange and metabolism; pulmonary iavage in ; iongterm extrapulmonary oxigenation with tleoroearboa oxygenator in combination whb ~trafiltra!ion, hemosorption and hemodialysis -in patients. results: pe~htoran increases blood volume, co,sv, decreases svr, improves capillary blood flow, increases the blood oxygen capacity, tissue oxygen tension, del, vo by improving the rheologic properties of blood and plasma, normalizes ext., prevents and eliminates fat embolisation and ards. decreases the need for blood transfusions and infusions of plasma expanders by . - . limes. alveolar venti!ation-perfusion ratio remains unchanged with its increased effective utilization. there was no surfactant destruction during lavage. extrapulmonary oxygenation of small volumes of venous blood eliminates venous destruction and then arterial hypoxia and increases pulmonary oxygenation. the use of lluorocarbon cxygenators during hemosorption and hcmodialysis provides the atraumatic and iongterm oxygenation of arterial blood and increases elimination of co which prevents the development of hypoxic complications. conclusions: perphtoran and fluorocarb~n oxygenators are effective in the correction of hypoxia in the criticat patients. objeqtives: to determine if there are differences in oxygen consumption (vo ) during weaning from mechanical ventilation (during total ventilatory support and spontaneous ventilation with cpap), and to compare different predictive parameters of weaning in predicting success of weaning. methods; prospective study in critically ill patients treated with mechanical ventilation for at least h, who fulfilled at least of standard weaning criteria (vt> ml/kg; respiratory frecuency (f) < ; pimax > cm h ; pao /fio > ). baseline measurements: t, vt, p . , pimax, f/vt, p . *(f/vt), p . /pimax. study protocol: measurement of vo , vco (medgraphics), vt, f, ve, and arterial blood gases during total ventilatory support (cmv), and after and minutes of spontaneous ventilation with cpap cm h . the weaning trial was stopped, failure to wean diagnosed, and mv resumed it a patient presented significant tachypnea, tachycardia, bradycardia, cardiac rythm disturbances, hypertension, hypotension, hypoxemia or hypercapnia. results: four patients did not complete the weaning trial, were extubatad, and of them had to be reintubated before h, being considered also weaning failures. during cmv, vo /kg was . + . ml/kg/min, and . _+ . mlo- /kg/min after ' on cpap cm h (p < , ). of patients ( %) with standard criteria were extubated, while only of ( %) with criteria (p< , ). next objectives: compare the extent and distribution of lung injury in dogs preinjured with oleic acid (oa) and ventilated with high tpp and adequate peep in the prone and supine position. methods: lung injury was induced with oa ( . - . ml/kg) in anesthetized, paralyzed, and intubated dogs (n= ) during volume controlled ventilation: rate= /min, peep= cmh , ti/ttot= . , fio = . , vt= ml/kg. animals were rotated during the oa infusion and the following minute stabilization period to assure uniform injury. in the supine position, peep was set - cmh above the lower inflection point (as determined by the pressure-volume curve), and vt was set to obtain a tpp of cmh : animals were ventilated in either the prone (n= ) or supine (n= ) position for four hours. pulmonary artery occlusion pressure was maintained constant ( - mmhg) with saline infusion. at the end of the protocol the lungs were removed and divided by template into dependent (d) and nondependent (nd) sections for wet weight/dry weight (v~n/dw) and grading of nstologic lung injury (hli; scale - ). oseillatron | is a pneumatic device that generates high frequency, oscillation by means of a reciprocating system in the form of a membrane. it generates sinusoidai wave form at ( to ( cycles/rain. the system does not deliver gas but must be adapted to the proximal respiratory, circuit of a conventional ventilator, resulting in ci-ifo. it was developed to enhance intrapnlmona~ diffusion during mechanical ventilation and to mobilise endebronchial secretions. methods. we measured arterial blood gases and haemedynamics during a first period of conventional ventilation (cppv) followed by. two rain periods of chfo (sequences : ( and ) c/rain : group l, n = l: and c/rain : group , n = ). measurements were made at the end of each period. cardiac output was measured using thermedilution method: flu and peep were kept unchanged throughout the study. intrinsic peep was also evaluated by, means of an occlusive valve. results. pa is not significantly modified during chfo at or c/rain. paco is slightly decreased at c/rain (p = .( ). however, intrinsic peep remains unchanged. there is no sequential effect (gr. l vs gr. ). there is no more effect of chfo for patieets who are at a flu higher than . (n = ). no changes in haemodynurmcs are observed except a slight increase in central venous pressure (cvp) during ci-ifo (p < .ol). obiectives: to examine the effects of inspiratory muscles unloading on neuromuscular output at controlled levels of chemical stimuli. methods: the ventilatory response to co was examined in ten normal subjects using rebreathing method. ventilation ~) and respiratory muscle pressure output (pmus) at the same end-tidal partial pressure of co (petco~) were compared with and without combined flow and volumeproportional pressure assist in two protocols (a and b). protocol a (n = ): two levels of assist were studied; flow assist (fa) of cmh /i/sec and volume assist (va) of cmh /i (assist ), and fa of cmh /i/sec and va of cmh /i (assist ). all conditions were applied randomly. v~, tidal volume (vt) and breathing frequency (f) were measured breath by breath and plotted as a function of petco~. protocol b: in subjects, in addition to above measurements, esophageal (pes) and gastric (pg) pressures were measured and the time courses of transdiaphragmatic pressure (pdi) and pmus were calculated. one level of assist (assist ) was studied in this protocol. results: in both protocols inspiratory muscle unloading did not change the f response to c%. compared to control, with assist v t response was displaced upwards; at petco of mmhg v t was increased significantly by . + . i and . + . i in protocol a with assist end , respectively, and by . _+ . i in protocol b with assist (p< . ). ~/~ responses showed similar changes as vtresponses. in both protocols the slope of v~ response (s did not change significantly with unloading. at low petco~ ( mmhg), pdi and pmus waveforms did not differ with and without assist. with unloading, at high petco ( mmhg), pdi and pmus at the end of neural inspiration decreased by . -+ . % and . + . %, respectively, from control values. neither change was significant (p> . ). by theoretical analysis we estimated the expected changes in vt and ~/~ when the levels of assist used in both protocols were applied in the absence of : any change in neural output response to co z. the predicted response was similar to that observed, indicating that the small difference in pdi and pmus between control and unloading runs was due to intrinsic properties of respiratory muscles end respiratory system. conclusions: these results suggest that when chemical stimulus is controlled, respiratory motor output is not downregulated with unloading. the determinants of the response of the respiratory output to inspiratory flow rates (v~) were examined in awake normal subjects. subjects were connected to a volume-cycle ventilator in the assist/control mode and v~ was increased in steps from to i/min and then back to i/min. v~ pattern was square, and all breaths were subject-triggered. in six subjects the effects of breathing route (nasal or mouth) and temperature and volume of inspired gas (protocol a) and in subjects the effects of airway anesthesia (upper and lower airways, protocol b) on the response of respiratory output to varying v~ were studied. in protocol b, in order to calculate muscle pressure during inspiration (pmus), respiratory system mechanics were measured using the interrupter method at end-inspiration. independent of conditions studied breathing frequency increased . significantly and end-tidal concentration of c% decreased as v~ increased. the response was graded and reversible and not affected by breathing route, temperature and volume of inspired gas and airway anesthesia. with and without airway anesthesia (protocol ) neural inspiratory and expiratory time and neural duty cycle, estimated from pmus waveform, decreased significantly as v~ increased. at all conditions studied the rate of change in airway pressure prior to triggering the ventilator tended to increase as v~ increased. the changes in timing and drive were nearly complete within the first two breaths after transition with no evidence of adaptation during a given ~/~ period. we conclude that v~ exerts an excitatory effect on respiratory output which is independent of breathing route, temperature and volume of inspirate and airway anesthesia. the response most likely is neu~'al in origin, mediated through receptors not accessible to anesthesia such as those located in chest wall or below the airway mucosa. it has been shown, in mechanically ventilated awake normal humans, that increasing inspiratory flow rate (~/~) exerts an excitatory effect on respiratory output. it is not known if this effect persists during sleep. to test this seven normal adults were studied during wakefulness and nrem sleep. subjects were connected through a nose-mask to a volume-cycled ventilator in the assist/control mode and ~/t was increased in steps ( - breaths each) from to i/min and then back to i/min. v~ pattern was square, and all breaths were subject-triggered. forty-one trials during nrem sleep and during wakefulness were analyzed. both during sleep and wakefulness minute ventilation increased and total breath duration (ttot) decreased significantly in a graded and reversible manner as ~' increased. these changes were complete in the first breath after v{ transition. the response was significantly less during sleep than during wakefulness (p< . ); at i/min ttot, expressed as % of that at i/rain, was . +_ . % during sleep and . +_ . % during wakefulness. during wakefulness, at i/min, the rate of change in airway pressure prior to triggering the ventilator, an index of respiratory drive, was % of that at i/min (p< . ). the corresponding value during sleep, was % (p> . ). in four sleeping subjects the increase in v~ was sustained for . - min. there was no evidence for adaptation of the response; tro t, averaged over the last three breaths, did not differ from that obtained when vj was sustained for only - breaths. we conclude that ) vt exerts an excitatory effect on respiratory output, mediated by a reflex neural mechanism and ) the gain of this reflex is attenuated by sleep. chest radiographs is a common complementary technique for patients in critical care units, with a low cost and easily available. however, it has certain well-known limits in diagnosis, the most important derived from the low quality of some pictures. in this paper we make a general review of some new technical approaches developed for improving the quality of the images, and so incrensing the diagnostic value of conventional radiology. we begin deaeng with the correct positioning of the patient, trough the filtering techniques, the synchronization of radiology and ventilation, and we make reference to the new computerized systems for digital image processing. conclusions: the portable radiographic system is a device that probably with maintain for many years in critical care units as a basic non-invasive diagnostic tool. but we need an increase in the efficiency of it, applying means as simple as a correct positioning of the patient, or the use of fitlers or synchronizers. thus we should improve the general standards of portable radiography. "are circular circuits safe? quantifying undelivered tidal volume in pediatrics patients". objectives: to evaluate the overall influence of internal compliance of circular circuits on delivered tidad volume (vt). methods: we studied prospectively asa i pediatrics patients ( to yr. old) scheduled for elective general surgery. mechanical ventilation was supplied by an ohmeda excel (circular circuit). the internal compliance of the circuit (cc)-anesthesia machine plus external circuit-was determined by the supersyringe method: corrugated dar tubes of mm. id and . m. long (children < kg), and a corrugated dar set of mm. id and . m. long (children > kg) were respectively used for ccl an cc values of . and . ml/cm h . a vtof mlg/kg and respiratory frequency was adjusted for an end-tidal co (etpco ) between mmhg. tidal volumes (measured by spirometry) and airway pressure (paw) data were recorded every ten minutes. volumes and thorax-lung compliances were calculated as follows: (vt delivered = vtadjusted-vol compressible, being vol. compressible = co x ppeak (aw). apparent compliance (ca) = vt adjusted/pplateau(aw), and true compliance (ct) = =vt delivered/pplatean(aw)). comparative statistics were separately designed between calculated compliance data and tidal volumes on a paired sample ~test basis. results: calculated values for volumes and thorax-lung compliances were: conclusions: due to the elevated internal compliance of the circular circuit there is a remarkable dilference between adjusted and delivered vt: mean undelivered vt was . % and reached as high as . %. teere is also a significative error in calculating true thorax-lung compliance: its overestimation can be as high as . %. circular circuits are considered safe and cost-saving for anesthetical practice. nevertheless we conclude that anesthetists should bearin mind vt losses when using circular circuits, due to compressible volume. tracheal stenosis is one of the most serious complications of patients submitted to prolonged endotracheal intubation, in which the decrease in inner diameter of upper airway makes it very difficult to achieve a correct ventilation. objectives: compare the results of applying high frequency jet ventilation (hfjv) to some of these patients with conventional controlled ventilation (cmv). methods: we used a prototype of high frequency jet ventilator (santiago- ) developed in our university, and we developed a tracheal tube in wich we modified the distal tip (conic tip). we applied this system to two patients which were initially ventilated in the operating room with usuai controlled mecanical ventilation (cmv) following the standards of our department, and then intubated with the special endotracheal tube and ventilated with hfjv. results: we could verify a proper ventilation of both patients with cmv and hfjv. during hfjv, the airway pressures were lower than those recorded during cmv. a lower airway pressure prevents lesions due to high pressures. conclusions: hfjv is a good method of ventilation for patients with significative stenosis of the trachea, not only during surgical procedures, but also during ventilation for long periods in critically patients. the ventilatory setting is pressure support mode. the pressure level and fit were kept constant during h/d. arterial blood gas, wbc count, and mean bp was checked according to the schedule: '(immediately before h/d), ', ', ', ', ', '. respiratory drive (represented by poa), tidal volume(ti) and minute ventilation(ve) were continuously recorded by pulmonary mechanics monitor (bicore cp- ). the mean value of the breaths minutes before blood sampling were used to represent the ventilatory status of that period. anova test is used for comparison between groups. for poa, hierarchical cluster method is applied to divide the cases into two groups of similar change. conclusions: our data suggest that pl is very useful, non invasive and low-expensive emergenc e support for arf, expecially in the elderly with severe chronic pulmonary disease and relative controindications to eti. pl seems to be an effective alternative when it is not immediatly possible to perform etl. the multiple inert gas elimination technique (miget) can be used to assess the effects of any given mode of mechanical ventilation on the pulmonary and systemic factors determining arterial po and pco> however, a potential problem in mechanically ventilated patients is that the l mixing box (mb- l) placed in series in the expiratory side of the circuit of the ventilator to sample mixed expired gas may provoke substantial discrepancies between the tidal votume set in the ventilator and the effective tidal volume delivered to the patient, due to the increase in the compression volume (vc) of the circuit. the effects of the mb- l on the v c were compared with those produced by a new l mixing box (mb- l) specifically designed to produce adequate gas mixing and to prevent loss of the two most soluble gases (ether and acetone) used in the miget. at any given peak cycling pressure (p~ak, cm h~o), the v c (ml) provoked by the mb- l was substantially higher (vc= . *ppeak) than that provoked by the new mb- l (vc= . *ppeak). at a ppeak = cm h ~ the v c were ml (mb- l) and m{ (mb- l), respectively (p< . ). in a group of subjects ( m/ f, _+ years), for each of six the gases used in the miget, the regression line between the mixed expired partial pressures simultaneously obtained from mb- l and mb- l fell on the identity line. it is concluded that the new mb- l allows adequate assessment of the effect of different modalities of mechanical ventilatory support on pulmonary gas exchange, with less potential for gas compression and thus hypoventilation. objectives evaluate the influence of different pressure support ventilation (psv) levels on cardiovascular and respiratory funcion in icu polytrauma patients. metbed&we studied polytrauma icu patients , who were in weaning process , after long term mechanical ventilation for acute respiratory failure . mean age ( - ) yrs . they all were connected to servo ventilators siemens c , and all were in stable condition , without sedation , inotropes or diuretics. the hemodynamic studies were done with continuous svo , swan ganz catheter (oximetrix, abbott). they all were in spontanuous mode (spent) with cm h cpap for at least one hour. we turned them to psv with inspiratory assistance (psv cm h ) and after rain we applied psv cm h , and after min psv cm h . hemodynamlo and respiratory measurements were done before and after the application of insiratory assistance. the results were statistically analyzed with anova. resets . respiratory variables . no significant changes in minute volume (ve). tidal volume (vt) and mean airway pressure (mpaw) increased statistically significant (p< . ) . respiratory rate (rr) decreased significantly (p< . ) . blood gase showed no difference . cardiovascular variables. cardiac output (co) decreased ns , heart rate (hr) had no change , central venous pressure (cvp) , mean pulmonary artery pressure (mpap) , pulmonary capillary wedge pressure (pcwp) , increased ns , oxygen delivery (do ) decreased ns, oxygen consumption (vo ) decreased ns. conclusions. psv is a very useful respiratory mode helping patients to be weaned from long term mechanical ventilation . it has beneficial effects on respiratory function and oxygen consumption without affecting seriously the hemodynamic parameters, possibly due to a decrease of the work of breathing. a. michalopoulos, a. anthi, k. rellos, j. kriaras, s. geroulanos intensive care unit, onassis cardiac center, athens. objectives of this study was to examine the effect of different levels of peep on postoperative svo and pvo values in a group of patients, following open heart surgery. methods: upon transfer to icu, patients ( males and females) of mean age _-+ years, were randomly assigned to receive (n= ), (n= ), or cm of peep (n= ). there were no statistically significant differences in demographic data or preoperative respiratory status among the three groups. all patients were ventilated on the assist control mode with a tidal volume of ml/kg. the fraction of inspired oxygen (fio ) was adjusted to keep a pao around mmhg. mixed venous po and svo were measured at min, and hours after application of mechanical ventilation in the icu, just before extubation (be), half hour after extubation (ae), and at hours post-extubation. differences at each study time were analysed by anova. results: mean svo and pvo values among the three groups, for all study intervals, are presented in the table. conclusion: we found no differences (p=ns) in tissue oxygenation (expressed by svo and pvo ) among the three groups, at any study interval, in the early postoperative course of patients following open heart surgery. intrinsic peep (peepi), and high elastance and resistance increase inspiratory work load in copd. cpap reduces work of breathing by counterbalancing peepi. pav provides flow (fa) and volume (va) assistance proportionally to patient resistance and elastance and inspiratory effort. we studied the effects of partitioned support (cpap-fa-va) on breathing pattern and inspiratory effort in five copd patients on pav compared to spontaneous ventilation (sv) and full support (fs: cpap+fa+va). flow, volume, minute ventilation (ve) respiratory rate (rr), inspiratory swing in esophageal pressure (apes), and its integral per breath (pti/b) and per minute (pti/m) were measured. objectives: to evaluate airway pressure fluctuation (apf) during spontaneous breathing in a high compliance cpap system. methods: the cpap system consisted of two l weighted balloons in a wedge shaped holder. ventilating gas flowed from one balloon through a low resistance one way valve into a tracheal tube (ett) provided with a pycor co sensor to monitor rebreathing. the ett was connected to a piston drive mechanical lung. expired gas flowed through a low resistance valve into a second weighted balloon, from where it was exhausted through a peep valve connected in parallel with the second weighted balloon. we evaluated system performance at v r from to ml, at rr from to bpm, while closely monitoring cpap airway pressure swings. at v v of and ml the rr was limited to bpm. for comparison we explored aps of a one l balloon cpap system, the cpap mode of the puritan bennett , and siemens ventilators, when connected to a healthy adult volunteer breathing through an ett. results: the compliance (cpl.) of one l balloon system was linear over a range from . to . l, with a cpl. of . l/em h .the cpl. of the l balloon ( . l/em h ) was linear between a volume of and . l. apf of the weighted balloon system was under em h at all v r (except at a v r of ml aps was . em h ), while the apf in the l balloon was up to em h . apf witli human volunteers with the two commercially available ventilators in the cpap mode was about cm h ; while under identical conditions apf in the l balloon system was . emhzo; and in the two l balloon system was below lcm h . conelusions: cpap using the two balloon system exhibits lower airway pressure fluctuations than a single balloon system; and is substantially lower than found in the two commercially available ventilators when used in the cpap mode. objective: to perform independent lung ventilation (ilv) with individual tidal volume (vt) set at a value generating a plateau airway pressure (pplat) < crnh~o and to evaluate the usefulness of the continuous monitoring of endtidal co (etco ) as a guide to titrate individual lung vt during ilv and for the weaning from ilv. methods: in seven patients, ilv was performed with ttvo ventilators set with the same fio: and respiratory rate. each lung was ventilated with a vt that developed a pplat < cmh~o. this setting led to a lower vt on pathological lung (pl). vt was increased in pl following etco~ and paco -etco variations. ilv was discontinuated when etco~., vt and statical compliance (cst) were similar in both lungs. results: one hour after starting ilv (ti), pl mean vt was significantly lower than in normal lungs (nl) ( + ml vs + ml, p< ) two individual behaviours were observed on tl in pl: four patients presented low etco: (range - mmhg)and normal pacoz (range - mmhg), while three patients had normal etco (range - mmhg) with high pac (range - mmhg). one hour before stopping ilv (t ), vt, etc and paco were the same in each lung. the pao /fio: ratio improved in all patients from the beginning ofllv cst of pl was + % of the normal lungs' cst on ti and improved to . + % ofnl's cst on t (p< . vs conclusions: setting vt of pl to a value not overcoming a pplat threshold does not impair oxygenation and is helpful in avoiding barotraumatism. measurements of differential etco and of the differential paco -etco gradient can be used to titrate vt allocation during ilv and as a guide for the weaning from ilv. total respiratory resistance in mechanically ventilated patients exceeds values obtained in normal subjects, due to the added and highly flow dependent resistance of the endotracheal tube (rett). this can adversely effect the efficacy of pressure regulated modes of assisted ventilation, such as pressure support (psv) and proportional assist ventilation (pav). recent work demonstrates that the influence of rett during psv can be overcome by using tracheal (ptr) rather than airway opening (pao) pressure to regulate the pressure applied (intensive care med :$ , ) . the purpose of this study was to see if this approach would also be effective during pav. flow, volume, pao, ptr, and transdiaphragmatic pressure (pdi) were measured in intubated patients in which either pao or ptt were used to regulate the pressure applied during pav where volume assistance was varied from to % of respiratory elastance. representative results (mean + se) are shown below. compared to spontaneous breathing (pav %), pav increased tidal volume (vt) while reducing respiratory rate (rr) so that minute ventilation ('~e) also rose. this was associated with a reduction in inspiratory effort, as reflected by a decrease in the pressure-time integral ( [ p) of pes and pdi both per minute and per liter ~re. the effects on breathing pattern were similar for pao and ptr regulated pav. in contrast, the reduction in inspiratory effort was always greater for ptr regulated pav. in conclusion, the volume assistance provided by pav is more effective when ptr rather than pao is used to regulate the pressure applied. pav methods: retrospective data analysis of adult patients with normal pulmonary function before operation and uneventful course following coronary artery bypass graft surgery over an month period. we compared assist/controlled mandatory ventilation (s-cmv, patients), synchronized intermittent mandatory ventilation with inspiratory pressure support (s-imv/psv, patients) and biphasic positive airway pressure ventilation (bipap, patients). results: patients ventilated with bipap had a significantly shorter mean duration of intubation ( . h, p< . ) than patients treated with s-imv/-psv ( . h) and s-cmv ( . hi. with s-cmv . % of the patients required single or multiple doses of midazolam but only . % in the s-imv-/psv group and . % in the btpap group. the mean total amount of midazolam of these patients was significantly higher in the s-cmv group ( . mg) than in the s-imv/psv group ( . mg, p< . ) and in the bipap group ( . mg, p< . ). the consumption of pethidine and piritramide did not differ between s-cmv and s-imv/psv but was significantly lower during bipap (p< . ). after extubation the paco patients was highest in the s-cmv group. conclusion: ventilatory support with bipap reduces the consumption of analgesics and sedatives and duration of intubation. unrestricted spontaneous breathing as well as fully ventilatory support allow adequate adaptation to the patients requirements. bipap seems to be an alternative to s-cmv and sqmv/psv ventilation not only in patients with severe ards but also in short term ventilated patients. _objectitives: after end-inspiratory airway occlusion we examined the ensuing gradual decrease in tracheal pressure (ptr) with the following equations proposed by bates et al. and hildebrandt: pv = p'v e'~cccl~ +pst, rs (bates) [ ] where p'tr is tracheal pressure immediately after occlusion, to= is occlusion time, "r is viscoelastic time constant of respiratory system, and p t is static elastic recoil pressure of respiratory system. p~(t) = h -h log t (hildebrandt) [ ] where h~ and h are parameters depending on lung volume, and initial time is s for analytical reasons. materials & methods: we studied healthy patients intubated, anestethized with propofol, paralyzed with vecuronium, and mechanically ventilated with constant flow ( . i/s) at zeep for minor surgery. pressure was measured in the trachea. flow was measured with a pneumotachograph and volume was obtained by numerical integration. the rapid occlusions were produced by an external valve. the signals were sampled at a frequency of hz and processed on a pc. the influence of the cardiac artifacts during the occlusion time ( s) was reduced by a software low-pass filter kaiser finite duration impulse response of elevated order. results: the mean (+ sd) coefficient of correlation using eq. was , -+ . , and using eq. was . + . . the values ofz~ (eq. ), however, decreased with increasing the tidal volume (vt) according to the following equation: "~ = . - . v t, similary, the values of h~ and h increased with increasing v t according to the following functions: h~ = . + v i and h = . + . v t. conclusions: the behaviour of "% of eq. suggests that the linear viscoelastic model is not sufficient to further describe the mechanical properties of the respiratory system over the vt range ( - ml/kg) in ventilated patients. infect this model predicts that "c is constant and independent of tidal volume. on the other hand the plastoelastic model is not sufficient to further describe the mechanical properties of the respiratory system. in fact "r obtained by fitting an exponential for data of eq. , is determined by the time of endinspiratory airway occlusion. obiectives: according to the viscoelastic model, the viscoelastic pressure of the respiratory system pv=rs during lung inflation with constant flow e~ is t/ r wh t lsms ira tlmeand r given by:pv~c.~ = d~( -'e-~ )[ ] ere " ' p" tory " and "r are resistance and time constant of viscoelastic unit. in the past, the viscoaletic constants were determinated by performing a series of occlusions at different lung volumes, or a sedes of occlusions at a fixed lung volume achieved with various inflation flows. in the present study we have developed a new method for determining "c and r which requires a single constant flow inflation. our method is based on determination of pv~r, during a single breath constant flow inflation, and of z during the ensuing end-inspiratory airway occiusion. dudng the occlusion the tracheal pressure p~, declines according the following function: ptr = p'lr e " too= " z + e~t.r= [ ] where p'~r is tracheal pressure immediately after occlusion, toc c is occlusion time, p,i.rs is static elastic recoil pressure of respiratory system, and ~ is viscoelastic time constant. we first determinated "~ by analyzing the time-course of ptr according to eq and next determining r according to eq. , using the expedmental values of p,i=~, ~ and ti, as well as "~ obtained with eq. . materials & methods: we studied healthy patients intubated, anestethized with propofol, paralyzed with vecurenium, and mechanically ventilated with constant flow ( . i/s) at zeep for minor surgery. pres-sure was measured in the trachea. flow was measured with a pneumniachograph and volume was obtained by numerical integration. the rapid occlusions were produced by an external valve. the signals were sampled at a fi'equency of hz and processed on a pc. the influence of the cardiac artifacts dudng the occlusion time ( s) was reduced by a software low-pass filter kaiser finite duration impulse response of elevated order. results: the mean coefficient of correlation with eq. was . . with v t of ml/kg, the mean values (+ sd) of ': and r of the subjects amounted to . • . s and . • . cmh i "~ s. with the traditional multi breath method the corresponding values were . + . s and . _+ . cmh i " s, respectively. with the t-test the difference between new and traditional "~ was statistically significant, between new and traditional r was not significant. conclusions: with the single breath method it is possible to compute ': and r . the mean values of r with v t of nd/kg, however, was slighuy different than those obtained with the traditional multi breath method. the application of modem principles of respiratory care and mechanical ventilation in icus has resulted in increased survival of critically ill individuals with neuromuscular, skeletal and irrevers~le pulmonary diseases. in these chronically ill individunts mechanical ventilation, long term therapy (ltot) and continuous home care is considered a chronic life supporltng technique that can not be withdrawn after their discharge from an icu. the aim of this study was to present the results of a rehabilitation programme and home care that runs in our ward. twenw three patients were referred to our clinic f~om icus during - . a specific rehabilitation programme designed according to individual's needs was performed. patients that benefitted from this programme were grouped into the following disorders. ) post tb respiratow failure ( %) ) neuromuscular diseases, ( %) } undiagnosed sas { %) ) cope) ( %) ( patients had a overlap syndrom). the programme consists of : ) assessment and mechanical support ff needed of the respiratonj system with non invasive methods (nasal or via tracheostomy). ) group and individual respiratory therapy ) mobilization ) nutritional support ) educational classes for the members of the family. three from the patients passed away (during the year), are under nippv during night with or without supply, pts recieve ltot. conclusion: the development of a programme for chronically ill individuals in especially designed wards in hospitals and the overall care at home is considered necessary at least in hospitals with icus. a rehabilitation programme and home care permits the fast but safe discharge of these patients from units of acute medicine that the cost of treatment is high and besides permits beds that are invaluable. we considered that the rehabilitation prod'amine and home care in our ward is the first performed in greek chronically ill pts and even though there is no special administxative support we think that the results are quite saltsfactory. objective: we postulated that the product of the respiratory frequency (f) and the ratio of inspiratory pressure (ip) to maximal inspiratory pressure (mip) would predict the weaning outcome in deeompensated copd patients better than either variable alone or other indices previously proposed. methods: in decompensated copd patients with difficult weaning, we measured, daily, respiratory mechanics data both during mechanical ventilation and after ten minutes of spontaneous breathing. then we calculated weaning indices reported in literature and some new integrated indices. according to the results of the discriminant analysis, we considered the integrative index crop (acronym of compliance, rate, oxygenation and pressure), the rapid shallow breathing index f/vt, the load/capacity ratio ip/mip, and the following new index: f x ip/mip. we used receiver-operatingcharacteristic (roc) analysis by calculating the area under the curve considered as the overall probability of correct classification. results: main results are reported in the following objective: to evaluate the reliability of some indices of endurance in predicting the weaning outcome of decompensated copd patients. methods: in decompensated copd patients with difficult weaning from mechanical ventilation (mv) we measured, daily, blood gas analysis, ventilatory and airway pressure pattern during mv, breathing pattern (frequency (f) and tidal, volume (v~)), inspiratory pressure (ip), and maximal ip (mip) during spontaneous breathing (sb). thereafter we calculated the following weaning indices: crop (compliance * mip * (pao /pao ) / f), flvt, ip/mip. data obtained the day at which the patient was considered ready for a trial of sb on clinical grounds but weaning failed (wf) and those obtained the day of the successful weaning (ws) were compared statistically through the wilcoxon rank-sum pair analysis. in order to quantify the predictive accuracy for each index with respect to successful weaning we calculated sensitivity, specificity, and diagnostic accuracy according with the standard formulas. methods : five patients ( + yrs) suffering from ards (lung injury score > . ) for hours or less entered into the study. irv (volume controlled, decelerating flow, % inspiratory pause, lie = / ) was compared to conventional ventilation (cv) (volume controlled, constant flow, no inspiratory pause, iie= / ). these two modes were applied for hours in a randomized order, with the same levels of total peep (peept = peep + peepi), tidal volume ( . • . ml/kg), respiratory rate ( • "bpm) mad fit ( • %). measurements (respiratory mechanics, hemodynamics, arterial and mixed venous blood gases) were performed after , , and hours of application of each mode. rvsuils : are expressed as mean + sem and compared by anova. backeround and methods: periodic breathing (pb) is characterized by repetitive cyclic variation in minute ventilation. pb is considewxl to be provoked by an instability in the respiratory control. inintubated, spontaneously breathing patients conventional modes of pressure support ventilation, i.e., triggered inspiratory pressure support ps), do not allow patients to breathe with theirinherent breathing pattern. therefore, pb, if existing, will appear mainiy after extubation. since our new mode of pressure support ventilation" automatic tube compensation" (atc) continuonsly corrects for the flow-dependent tube resistance during insnmdon and expiration ("electronic" extubatim), it pemaits patients to maintain their own inherent breathing pattern. then, ff necessary, tracheal pressure can be additionally supported by volume-proportioead and/or by flow-proportional pressure support (proportional assist ventilation, pav). (~as~: we report the case of a -year-old male patient who was intubated due to acute respiratory insufficiency after acute myocardial infarction with left ventricular dysfunction. during ips of mbar the patient showed a regular breathing pattem which became periodic during atc. in addition, proportional assist ventilation of mbar/l increased periodic breathing in such a way that the typical cheyne-stokes breathing pattem occurred (see figure) . baqkground: the hering-breuer reflex (hbr) is characterized by an inhibition of inspiration during lung inflation. this response has been recognized as an important vagally mediated mechanism for regulating the rate and depth of respiration in newborn mammals. in adult man the hbr is considered to be active only at lung volumes well above functional residual capacity, i.e., at tidal volumes above ml. assessment of the hbr requires specialized methods such as single breath or multiple occlusion technique. methods; in the presence of desynchronization between ventilator and patient, which frequently occurs during triggered inspiratory pressure support ventilation (ips)(see figure) , prolongation of the interval between inspiratory efforts (indicated by negative deflection of the esophageal pressure) due to lung inflation exposes an active hbr. we examined the occurrence of hbr in intubated critically ill patients. strength of hbr was assessed by the formula: prolongation [%] = ((inspiratory interval of interest -preceding inspiratory interval)/preceding inspiratory interval) * ( . rr of patients examined showed moderate to severe desynchronization. in of these patients a (re)activation of the hbr was found. the strength of hbr amounted to + %. there was a significant correlation between tidal volume and strength of hbr. in contrast to previous reports, an active hbr was shown during lung inflation well below ml. b pck~round: triggered inspiratory pressure support ventilation (ips) is commonly used to support inspiration in intubated spontaneously breathing patients. despite its usefulness ips shows some disadvantages which can be deleterious in crificauy ill patients: -additional work of breathing to be performed by the patient due to the flow-dependent tube resistance -desynchronization between patient and ventilator due to inherent triggering failures of the ips mode suppression of the patient's inherent breathing pattern -inability to predict successful extubation in difficult-to-wean patients methods: based on the known flow-dependent tube resistance our new mode "automatic tube compensation" (atc) compensates for the pressure drop across the endotracheal tube ("electronic" extubation). then, if necessary, tracheal pressure can be supported by volume-proportional pressure support (vpps) and/or by flow-proportional pressure support (fpps). results: hitherto, we have examined patients after open-heart surgery and patients with acute respiratory insufficiency (ari) or ards using atc with/without vpps/fpps. preliminary results suggest that the new mode avoids additional work of breathing due to accurate compensation of the pressure drop across the endotracheal tube during in-/expiration prevents desynchronization between patient and ventilator allows patients to breathe with their inherent breathing pattern accurately predicts the outcome of extubation even in difficult-to-wean patients due to "electronic" extubation conclusions: the new mode atc with/without vpps/fpps allows to support ventilation in a more physiologic manner and overcomes the disadvantages of conventional modes of pressure support in intubated patients. backgound: cheyne-stokes respiration (cs) is characterized by regula]; recurring periods of hyperpnea and apnea. in normal subjects, cs may occur after hyperventilation, after arrival in high altitude, or during sleep. it has also been observed in patients with prolonged circulation time due to congestive heart failure, as well as in some neurological patients. there is no report about the influence of sedative drugs on periodic breathing (pb) and cs. methods: in intubated patients conventional modes of pressure support do not allow patients to breathe with their inherent breathing pattem. therefore, periodic breathing and cs are rarely seen. since our new mode of pressure support ventilation "automatic tube compensation" (atc) continuously corrects for the flow-dependent tube resistance during inspiration and expiration ("electronic" extubation) it permits patients to maintain their own inherent breathing pattem even if pathological, e.g., periodic. results: using this new mode of pressure support ventilation, periodic breathing was unmasked in of intubated patients, of which showed cs. in of these patients the occurrence of cs was linked to impaired left ventricular function with increased circulation time. normal left ventricular and neurologic function was found in the remaining patients. in of these patients cs disappeared after intravenous administration of the benzo-diazepine antagonist flumazenil (figure). consequently, in this patient cs was induced by benzodiazepine sedation. objecti',~s: in contrast to conventional rhodes for pressure supported spontaneous breathing, our newly developed ventilatow mode ,,automatic tube compensation" (atc) completely compensates for the flow-depandant pressure drop tlpm-r across endotracheal ttlbe (ett). in the atc mode, the ventilator supplies a flow v' in order to maintain a constant tracheal pressure p~,,~. to this end, pk,,= has to be oontinuousiy determined. since continued measurement of p,,~ by introducing a catheter via the ett is not reliable, we opted for its continuous calculation socordng to the following equation: p~ = p,,, -aperr, pw being the continuously measured airway pressure. this also requires the continual measurement .of flow v' to calculata apm-r using the non-fineer approximation: aport = kvv' + k .w. the constant tube coefficients k~ and k are mathematically determined by mesns of a least-squares-fit procadum based on laboratory investigations. tracheal secretions, however, reduca the omss-saction of the ett. consequently, ~ values of ki end k are changed rendering the p~,ch calculations inaccurate. therefore, k and ~ have to be pedodcally updated to ensure an a~urete monitoring of pn,~ and a complete tube compensation under atc at any time. background: one of the first steps in weaning patients from controlled mechanical ventilation is to stop muscle relaxation and to reduce sedation. it can take several hours, however, until the patient is able to trigger the ventilator and to breathe spontaneously. during this period, many patients display a sudden increase in peak airway pressure of up to %. patients and methods: to investigate the reason for this potentially dangerous effect, we continuously measured lung and chest wall mechanics in post-operatively ventilated patients. lung mechanics (airway resistance and lung compliance) was measured using the esophageal balloon technique as described in [ ] . chest wall mechanics (tissue resistance and chest wall compliance) was calculated from lung mechanics and total respiratory system mechanics as described in [ ] . results: we found a decrease of chest wall compliance (cw) to be the main reason for episodes of sudden airway pressure increase while lung compliance (cl) remained unchanged. the decrease of c w can be inter- gil cano a, san pedro jm ~, sandar d, herntndez . , carrizosa f, , herrero a. emergency and intensive care department, hospital of jerez, spain objective: ) to determine the incidence of hypoteasion (h) associated with emergency intabatian of mechanical ventilation, and ) to establish its relauonship with respiratory mechanics (rm) and arterial blood gases. mechanical ventilation performed in the emergency room, in a prospective eans~eative manner, were evaluated. data collected included patient demographics, diagnoses, blood pressure and arterial blood gas levels before and at~er intabatian, and p_m, including calculated pulmonary end-inspiratory volume above functional residual capacity (veic) and calculated dynamic hypetinflatien (dhc). all patients received midazolen and awaanrinm to facilitate tracheal intubatien and rm measurement. hypotension was defined as a decrease in systolic pressure higher than mmhg or an absolute decrease in systolic blood pressure below to mhg within hour of intabatian. patients were excluded because met at least one of the following exclusion criteria: preexisting shock or h ( ), cardiac arrest ( ) . there weren't any association between peepi or other airway pressures (paw) and h, but calculated pulmonary volitmes had tendency to be larger in patients with h (p < . ). high paco before lrasheal intubatian ( . - mmhg) with a quickly decrease alter starting mechanical ventilation was a usual finding (p < . ) in patients who developed h. paw. ) thexe was a good relatienship between h and high arterial paco before traqueal intahatian and its fast "washing" with mechanical ventilation. ) because cao patients had the highest incidence of h, controned mechanicel hypoventilatien driven by paco changes and pulmonary volumes monitoring instead paw, should be attempted in these patients to avoid this cemplication after tracheal intubatiert. introduction: the endotracheal tube (ett) and demand valve devices cause an added work of breathing (wobadd), which is the work necessary to overcome the resistive load of the ett and the breathing circuit ( ). application of ips has been shown to partly compensate this added work ( ). since tbe amount of wobadd is flow dependent, a fixed ips is not adequate to completly compensate the wobadd ( ). therefore, atc has been developed as a new form of assisted spontaneous breathing ( ), which provides a flow-dependent pressure support. thereby, it theoretically should compensate all the wobadd due to the tube. the purpose of this study was to evaluate the reduction of wobadd with ips and atc for different ett. methods: a mechanical lung model (ls , dr*alger, liibeck, frg) was used to generate a constant spontaneous breathing pattern. the ls was connected to an artificial trachea (at, cm long, mm id). the at was intubated with three different tubes of . , . , . mm id and connected to an evita ventilator modified to provide atc as an option (dfager, liibeck, frg). flow and airway pressure were measured between the y-piece and the ett for four different modes of ventilation: cpap, ips of and cm i and atc all with a peep of cm h . the tracheal pressure (ptrach) was measured in the at. total wobadd was calculated as the area subtended by the ptrach-volume curve below peep. results: the results for total wobadd in nd/ are shown in the figure for the three different ett: breath/mln, s=success, f=failur% *~p<. , **-p< , ns = non significant, f versus s neveltheless, in / patients, invasive ventilation was necessary in mean . _+ hours after beginning of fmpsv. there was no significant difference between the two groups (success, failure) in following parameters : sex, age, previous histoly, medical treatment, saps & , clinical signs (rr, spo , heart rate, blood pressure, glasgow score...), radiological and echocardiographic findings and standard biological parameters. only two parameters were related with failure : .a low value of pac on admission until the patients were intubated. . an increased level of cpk in relation with an acute myocardial infarction ( / cases in the failure group, vs / cases in the success group, x~(with continuity correction) : p<. ). conclusion : fmpsv is a noninvasive, safe, rapidly effective method of treatment in acpe, which may avoid tracheal intubation. further studies are necessary to precise if association of arf and low paco (< mmhg) and/er acute myocardial infarction represents an indication of immediate invasive ventilation. introduction: since the added work of breathing (wobadd) imposed by the endotracheal tube (ets and the breathing circuit is regarded as an important contribution to the total work of breathing, considerable effort has been tmdettaken to compensate for this added work. ips has been fotmd to decrease the wobadd imposed by different ventilators ( , ). because of the flow dependent pressure drop across the etf the tracheal pressure (ptr) should be measured to estimate the total imposed wobadd (wobtut) ( , ). the aim of this study was to assess the circuit imposed work (wobcirc) and wobtot (including ett) for different demand valve ventilators during cpap and/ps. methods: a mechanical lung model (ls , driiger, lfibeck, frg) generated a constant spontaneuus breathing pattern. the ls was connected to an artificial trachea (at), intubated with an . nun et]', end connected to one of four ventilators (servo c and servo , siemens,-elema, sweden; evita , driiges, liibeck, frg; pb ae, puritan bennett, carlsbad, usa). three different modes of ventilator settings were tested (cpap, ips and mbar; trigger set at maximal sensitivity, peep always mbar). flow and airway pressure (paw) were measured between the y-piece and the etr; tracheal pressure (ptr) was measured in the at. wobtot was calculated as the area under the ptr-volume curve below peep, wobcirc was calculated as the area under the paw-volume curve below peep. results: in the foti g., patroniti n., cereda m., sparacino me., giacemini m., pesenti a. inst.of anesth.and intensive care-univ.of milan -sgh monza i aim of the study was to assess cpl,rs measurement obtained by the airway occlusion method during psv. we therefore studied paralyzed cppv ventilated ali patients (lung injury score = . • that were weaned to psv. we performed end inspiratory and end expiratory airway occlusions using the hold function of the ventilator (siemens serve c), first during cppv and then within the th psv hour. airway pressure and flow signals were recorded (cpi bicore) for subsequent analysis. an airway pressure plateau was defined as a flow tracing in which airway pressure was stable for at least . sec. end inspiratory (pel,rsi) and end expiratory (pel,rse) recoil pressures were then measured as the mean airway pressure during plateaus. cpl,rs was computed as tv/ (pel,rsi-pel,rse i) cpl,rs can be adequately estimated during psv using the airway occlusion method; ) during psv inspiratory plateaus are longer than the expiratory ones; ) the length of plateaus is negatively affected by the respiratory drive. foti g., de marchi l., *tagliabue m., gilardi p., giacomini m., sparacino me., pesenti a. inst.of anesth.and intensive care,-univ.of milan *dept.of radiology-sgh monza i we retrospectively compared ct scan and gas exchange findings between a group of patients successfully weaned from vcv to psv (group s = ii patients) and a group who failed the weaning (group f = patients). we selected ali patients (lis= . • in vcv mode who had available a chest ct scan performed within days from the weaning trial. a psv trial was began as soon as the patient reached hemodynamic stability and a pao > mmhg, irrespective of fie (peep < cmh ). maximum psv level was < (pel,rs-peep) measured during vcv, where pel,rs was the respiratory system elastic recoil pressure at end inspiration. psv ventilation was considered successful if a respiratory rate < bpm, an increase in fie lower than . compared to vcv, a pace increase < % of vcv value and hemodynamic stability were maintained during the next hours of psv. if any of these conditions was not met the trial was declared a failure. interdisciplinary critical care unit, regional hospital lugano-ch *surgical critical care unit, university hospital, geneva-ch objective: to assess the degree of correlation of cardiac output measured by thoracic electrical bioimpedance and thermodilution in mechanically ventilated patients with different levels of positive end-expiratory pressure (peep). methods: prospective study with ventilated patients, after head injury and with postoperative sepsis, with normal cardiac output: simultaneous determination of cardiac output by thermodilution and thoracic electrical bioimpedance performed with different levels of peep ( - - cm h ). results: cardiac output measured by thermodilution during sequential increment of peep did not vary: . + . for peep , . + . for peep and . + . l/rain for peep . simultaneously the bioimpedance device recorded a significant increase in cardiac output from . + . for peep to . + . l/mi for peep . (p < , ). conclusion: cardiac output measured by bioimpedance cannot replace the invasive thermodilution methods of cardiac measurement output during mechanical ventilation with peep. we also isolated a subset (h) of patients who had been hypercapnic (paco > mmhg) for at least days (range to days) before the end of cv. the psv trial was started as soon as pao was > mmhg, irrespective of fie and with peep < cmh and the psv level had to be < (pplateau-peep) as measured during cv. pace , pha, base excess (be) were collected before discontinuation of cv and on the ist day of psv: ) . ) weaning is more difficult in pts with head injury(p<o, ) and iss> (p<o,ol), in elderly(p<o, ) and in pts who need fi > , (p<o, ) and peep>io cm h (p<o, ). ) pts with iss> need longer duration of mv (p<o,ol). ) the mortality rate is higher in pts with iss> (p<o,o ), with head injury (p<o,ol) and in elderly (p<o, ). ) paradoxally, compliance was found to be higher in pts> years than in pts< years (p<o, ). s. crotti, p.pelosi, d.mascheroni, m.cerisara, a.lissoni, l.gattinoni. istituto di anestesia e rianimazione -irccs, milano, italia. obiectives. we investigated by ct scan the effects of extrinsic peep (peepe) on lung inflation, tidal volume distribution and regional compliance in sedated, paralyzed chronic obstructive pulmonary disease (copd) patients with dynamic hyperinflation (peep• methods. two ct section (end expiration, end inspiration) were obtained at lung base level in patients (individual analysis for each of the eight lungs) at peepe levels: peepe = cmh (zeep) and peepe amounting to %, % and % of the peep• at zeep ( . • cmh ). tidal volume was kept constant ( • . ml/kg). each lung section was divided into zones equally spaced along the vertical axis: upper (the most ventral), middle and lower (the most dorsal) zone. for each zone we computed: gas volume at end expiration (gase) and at end inspiration (gas• tidal volume (dgas=gasi-gase) and compliance (cpl=dgas/dp;.dp=plateau pressureactual peep• we also computed the lung inflation as the entire ct section gas volume at end expiration (total gase). results. at each peep level both gase and gas• were higher in the upper than in the lower zone ( we cone!ude that in copd patients with dynamic hyperinflation only the application of peepe higher than peepi produces a further increase of lung inflation, decreasing cpl of the upper zone (the more expanded one) probably by stretching phenomena, and causing dgas redistribution from the non dependent to the dependent lung zones. i. ravagnan, p. vicardi, f. valenza, d. tubiolo. p. pelosi l. gattinoni. st . anestesia e rianimazione, universita' di milano, ospedale maggiore -irccs, italy objectives: to investigate the effects of peep and ps on respiratory. pattern and inspiratory effort during ps ventilation in patients with acute lung injury or acute exacerbation of chronic lung disease. methods: pts with acute (a) (paco = • mmhg, pao /pao = . • and pts with chronic (c)(paco = • mmhg, pao /pao = . : . ) lung disease were studied in ps ventilation during the weaning phase. measuring airway pressure, esophageal pressure and gas flow we computed respiratory rate (ril bpm), tidal volume (tv, ml) and pressure time product (ptp, cmh *s/min), which is an index of oxygen muscle consumption. measurements were collected, after rain of stabilization, at and cmh ps and at two different peep levels ( and cndd conclusions: during psv: ) breathing pattern and ptp are different between a and c; ) in both groups peep does not modify breathing pattern; ) peep reduces ptp in c but not in a; ) ps modifies breathing pattern and reduces ptp in c but not in a. to test the performance of a new heat and moisture exchanger (hme): twistair, baxter. this is a hydrophobic-hydrophilic hme without hygroscopic salts. method: we evaluated the hme performance with a previously described method (i); it consists of a "lung simulator" connected to a mechanical ventilator and a flow divider, with a dry and a wet thermal probe inserted into inspiratory and expiratory limbs. on average ps level changes were associate( with opposed changes in both p . and rr. changes in p . were remarkable, homogeneous and highly significant (p<. ), while changes in rr were less pronounced, inhomogeneous and less significant (p<. ). it seems therefore that p . is a better index than rr for estimating a change in load for the respiratory muscles. recently, the lsf method has been described as an interesitng alternative to conventional tecniques used to measure total respiratory mechanics, providing, over these latter, advantages such as no need for hold maneuvers and no need for particular flow patterns. data on the reliability of the lsf method, however, are still few. methods. sets of measurements were obtained in each of ards patients, paralyzed and ventilated in cmv with constant inspiratory flow and an end-inspiratory pause equal to % of ttot. the lsf method provided data for total compliance (ctotlsf) and total resistance (rtotlsf) by multiple linear regression analysis of airway pressure, flow and volume change, applied over the entire breath. the lsf measurements were automatic and continuous, and each value used for analysis was the average of consecutive cycles. conventional measurements of dynamic.compliance (cdyn), quasistatic compliance (cqs), minimum inspiratory resistance (rmin) and maximum inspiratory resistance (rmax) were obtained by the constant flow, end-inspiratory occlusion method, each value being the average of measuremts. ctotlsf was compared with cdyn and cqs, while rtotlsf was compared with rmin and rmax. results. ctotlsf showed a high correlation both with cdyn (cdyn=. .ctotlsf+l. , r =. ), and with cqs (cqs =. .ctotlsf + . , r =. ). the average difference between ctotlsf and cqs, yet, was much lower (+. + . ml/cmh ) than the one between ctotlsf and cdyn (+ . + . ml/cmh ). rtotlsf correlated much better with rmax (rmax=. *rtotlso+. , r =. ) than with rmin (rmin =. .rtotlsf +. . , r =. ). the average difference between rtotlsf and rmin was + . + . cmh / /s, while the one between rtotlsf and rmax was +. + . , confirming the better agreement between rtotlsf and rrnax. conclusion.the agreement between rtotlsf and rmax suggests that rtotlsf takes into account both the airway and the tissue components of resistance, unlike rmin which only expresses airway resistance. the agreement between ctotlsf and cqs indicates that ctotlsf expresses the pure elastic components of the respiratory system. in the paralyzed patient, the expiratory time constant (rce) of the unit represented by total respiratory system and ventilator can be calculated from the slope of the expiratory flow-volume curve. recently it has been suggested that an estimate of this slope is provided by the ve/v'epeak ratio, ve being the exaled tidal volume and v'epeak the peak expiratory flow.the reliability of this method is still little known. methods. sets of measurements were obtained in mechanically ventilated ards patients during paralysis and cmv. measurements of ventilator expiratory resistance (rext) and of total respiratory mechanics were performed in order to calculate these reference measurements for ve/v'epeak: rcdyn=(rmin+rext)ocdyn, rcstat=(rmax+rext)ocqs, rclsf=(rlsf+rext)~ cdyn (dynamic compliance), cqs (quasistatic compliance), rmin (minimum inspiratory resistance), rmax (maximum inspiratory resistance) were obtained by the constant flow, end-inspiratory occlusion method. clsf and rlsf respectively corresponded to measurements of total respiratory system compliance and resistance by the least squares fitting method. ve/v'epeak showed a high correlation with all reference measurements, rcdyn (ve/v'epeak= . orcdyn-. , r =. ), rcstat (ve/v'epeak = . rcstat -. , r = . ), and especially rclsf (see fig the static pressure volume curve of the respiratory system (p/vst) provides valuable information, but the extensive data analysis prevents its use in clinical routine. dynamic p/vcurves are simpler to record. the objective of this study was to develop an automated method to obtain quasi-static p/v-curves (p/vqs) during low flow inflation as well as to measure resistance. preliminary tests were done in normal subjects and subjects with varying degree of lung disease. methods: a computer/ventilator interface (cvl) was constructed for control of a servo ventilator c during an automatic sequence: a) a normal breath, b) a prolonged expiration at zero peep, c) a low flow inflation of a predetermined volume, d) analysis of ventilator pressure and flow. pressure was corrected for tube resistance. airway resistance was calculated from a) and used to derive p/vqs from c). as reference, p/vst was obtained by the occlusion method. results: in non-obstructive diseases the method performed well at volume and pressure controlled ventilation. static and quasistatic compliance were virtually identical. p/vqs clearly reflected the lower inflection point and, when present, the upper inflection point (uip). in some patients uip was more evident in p/vqs, especially at an increased inflation flow rate. in obstructive diseases, the method for subtraction of resistive pressure was inadequate. conclusions: the system for automated computer controlled studies of lung mechanics based on a standard ventilator provides comprehensive information. differences between p/vst and p/vqs imply that the latter reflects also other factors than p/vst that contribute to impedance at hyperdistension. the clinical significance of the two curves remains to be shown. obiective: to evaluate the effect of combined high frequency jet ventilation (chfjv) in patients with severe respiratory insufficiency (sri). methods: in a retrospective study of the period - we analyzed patients suffering from sri who were refractory to conventional mechanical ventilation and were treated with combined high-frequency jet ventilation (chfjv). refractory to conventional mechanical ventilation was defined as a pao /fio < , despite maximal ventilator settings: peep > cm hz , fit > . . a total of patients matched these criteria, males and females with a median age of ( - ) years. seventeen suffered from severe trauma. chfjv was started following a median period of ( - ) days of conventional mechanical ventilation. prior to chfjv ventilation parameters expressed as median were the following: fit . , pao /fio , peep cm h peak airway pressure (pap) cm h . chfjv consisted of high frequency jet ventilation with a frequency of to breaths/minute, driving pressure of . to . arm, and inspiration time of to percent, superimposed on the whole cycle of conventional mechanical ventilation with a frequency of l to breaths/minute and tidal volumes of to ml. results: following two days of chfjv of patients showed an improvement of ventilatory parameters; peep could be reduced to < cm h in patients, the pap was decreased with > cm h:o in patients, fio could be reduced to < . in patients and finally the median pao /fio ratio changed from to . during chfjv patients died, of respiratory failure and due to multiple organ failure, died within two days of chfjv. the median duration of chfjv in survivors and nonsurvivors was days in both groups. conclusions: our data show that with chfjv in the majority of patients with sri who are refractory to conventional mechanical ventilatior" the ventilatory parameters can be improved. backeround and obiectives: although ventilation with peep above the inflection point (pinf) has been shown to reduce lung injury by recruiting previously closed alveolar regions, it carries the risk of hyperinflating the lungs. in the present study we set out to develop a new strategy to recruit the lung during ventilation with small vt, while maintaining peep levels as low as possible. we hypothesized that if the lung was recruited with a sustained inflation (si) to total lung capacity, recruitment would be maintained as long as the peep level was higher than the critical closing pressure of the lung, as observed on the deflation limb of the pv curve (ajrccm ; ( ) :a ). the purpose of this study was to examine the hypothesis that a strategy using si and a peep<pinf would induce less lung injury during small tidal ventilation than ventilation at the same low peep level without using a recmitment strategy in a model of respiratory distress syndrome. methods: we used a randomized protocol with groups to ventilate nonperfused, lavaged rat lungs with small vt ( to ml/kg) for hours and studied the effect on compliance and lung injury. group : peep>ping group : peep<pin f with an si, inflation to on h over sec, to recruit volume; group : peep<pinf without si; group : control group, lungs were inflated at peep<pin f, but not ventilated. results: in group and group static compliance did not change after ventilation (table) . in group static compliance fell significantly. group showed significant changes in the pv curve, which were less severe than in group . results from morphological examination are pending but preliminary results showed less lung injury in group , compared to group . conclusions: small tidal ventilation following a recruitment manoeuvre in a model of respiratory distress syndrome allows ventilation on the deflation limb of the pv curve at a peep below pinf. this strategy ( ) minimizes lung injury as well as, or better than using peep above pint" and ( ) ensures a lower peep to minimize the detrimental consequences of high lung volume ventilation. i~peep>pin~ _objectives-this report is presenting the results of the clinical study for using eeg examination as a method of the evaluation of patients ability for weaning. methods: the study inclljqles eeg examinations with fourier spectral analysis' of patients ~vith respiratory insufficiency and prolonged control mechanical ventilation (cmv). all patients have had a-rhythm of eeg before weaning. we have followed respiratory rate, tidal volume, respiratory pa{tern, end-tidal co and blood gases during weaning. results: patients had invariable eeg activity or short -waves period (till one hour). the weaning of this patients was fast arid sucsessful. other patients have had a decreasing of a-activity, an appearence of -waves for an hour and more, a short episodes of a-and e-activity. after that this patients had gas exchange and respiratory disorders with regression of the weaning right up to cmv. conclusion: eeg could be used as a method of the evaluation of patients ability for weaning from cmv. some eeg signs shows the overstrain of compensatory systems before the change to the worse of gas exchange and respiratory pattern. s. elatrous, p. aslanian, d. touchard, d. corsi, h. lorino, l. brochard. medical intensive care unit, inserm u , hopital henri mender, cr~teil, france. in vitro comparison of flow triggering (ft) systems demonstrated advantages compared to pressure triggering (pt) systems for some ventilators (puritan bennett ) but not others (siemens serve ). we studied the two types of systems in two groups of patients mechanically assisted with pressure support ventilation ( + cmh ). in the first group (pb ) the effort of breathing, assessed by the esophageal pressure time index, was significantly lower with the ft than with the pt ( + cmh .s/min - vs + , p< . ). by contrast no significant difference appeared in the second group (serve ), as predicted by the bench study despite marked interindividual differences ( + cmh .s/min - vs + , p = . ). we conclude that ) rigorously performed bench studies can predict in vivo effects, ) mild advantages can be found for the new triggering systems on some ventilators. objectives: pressore-volume curves (pv) of the respiratory system is of interest for the determination static compliance (cs , lower (lip) and upper (uip) inflection points which indicate zones of airway recruitment and overdistension. this study aimed to compare an "automated low flow inflation" method (alfi) to the reference occlusion (oc) method. the ability of the former method to identify cst, lip and uip was tested in icu patients. me,otis: ( arf and ards) sedated paralysed patients were studied using a serve c ventilator linked to a computer which automatically forced the ventilator to insufflate at a low constant flow a velum up to - ml or a maximum paw of cm h (alfi). the quasistatic elastic pressure (pel,qs was obtained by subtraction of the resistive pressure of tubing and patient and related to volume for calculation of compliance cqst. for oc tidal volumes (v from up to - ml were followed by a s post-inspiratury pause for determination of static pal (pel,st) in relation to volume. compliance was defined from the linear part of the p/v curves. lip and uip were defined from the consistent deviation of p/v data from extrapolated the linear part. ~,~ i~: in ards, mean cst was . + . and cqst . + . ml/cm h (us), lipst . + . and lipqst . + . cm h (us), uipst . + . and uipqst . + ~ cm h (us). nosocomial pneumonias (np) are frequent and often unsuspected during ards (bell, ! ). in the present study, we evaluated prospectively the onset of np during severe ards (group b of the european study). patients and methods: the charts of patients with severe ards have been prospectively recorded. a plugged telescopic catheter (ptc) specimen has been systematically performed every hours, for quantitative bacteriological analysis. the diagnosis of np was defined by a number > colony forming units / ml. results: for the patients studied, the mean saps score (+ sd) was +_ , the initial pao /fio ratio was -&-_ , the duration of mechanical ventilation (mv) was + days. the mean delay before the onset of the first np was . + . days ( - ), and the mean pao /fio ratio was +- . respiratory symptoms (purulent aspirates, new pulmonary infiltrates, or gazometric changes) were present in % of the patients studied. alteration of gas exchange was present in of the patients ( np) . a new pulmonary infiltrate was present in only np ( %). an increase of fever was noted in patients, an increase of leukocytosis > % in patients, an increase of volume and purulence of sputum in of the patients with np. the degree ofgazometric worsening (pao /fio before np minus pao /fio during np) during the first episode of np was + mmhg. excluding the bacteriological criteria of np, the number of criterias of np present was in / patients, ( / ), ( / ) or ( / ). two patients only had a pulmonary colonization (ptc: < cfu / ml) before the first episode of np. the incidence of np is high ( %) during severe ards. the first episode occurs in average:at the th day, and is the cause of a severe hypoxemia (pao /fio ) . the onset of a np may contribute to the high mortality rate observed in our patients ( %). each worsening of hypoxemia during severe ards should induce to suspect a np. respiratory system during mechanical ventilation. the me~hod quantifies the dissipative energy consumption of the respiratory system in terms of energy loss aek, inefficiency ~k~ and respiratory dissipative resistance rk~ over a given partition of the tidal volume. the method can be applied in intensive care units with no interference to ventilatory support. it allows for monitoring the combined effects of inhomogeneities, non-linearities and visco-elastic effects, that are subject to change in the respiratory system. the method is studied on pigs~ in the presence of a log-dose response curve of methacholine (mch) induced disease. in healthy pigs~ we find a mean value of energy loss, ae, of . • j/l, a mean value of inefflency, ~ of . ~= . and a mean value of resistance, ~, of . • cm h s/ . the respiratory resistance, rk, shows a variation over the partition of tidal volume with armax ---- . • . cm h s/l. during methacholine provocation~ ae rises more than five-fold up to . • j/l~ doubles to . • and t~ increases to a maximum of • cm h s/l, with armax : . • . cm h s/ . the variation in rk becomes more pronounced with higher doses of methacholine. methods: ards patients were prospectively studied. initially they were ventilated in the amv (assist mechanical ventilation) mode with the settings prescribed by their primary physician. after stabilization, ventilatory gas exchange and hemodynamic variables were determined. patients were then ventilated in the mrv (mandatory rate ventilation) mode with breaths as the target rate. in mrv the target rate is set and the ventilator autoregulates the pressure support level delivered ~o achieve this rate. after stabilization, the measurements done on amv were repeated. finally, patients were sedated and paralyzed and ventilated in cmv (control mechanical ventilation) with the ventilatory variables they had during mrv. measurements done in amv and mrv were repeated and respiratory mechanics were assessed with the constant flow end inspiratory occlusion method. results: two groups were recognized based on their response to mrv. tn group patients responded to mrv by decreasing their v and increasing the t/t t ratio. ve, vo , and aado decreased while paco increased and tda vo ume and co remained unchanged. on the contrary, in group v, vr and ve increased; ppeak and trr t remained unchanged, paco~ decreased while vo and aado increased with constant co, the pressure support level needed to achieve the target rate was much lower in group than in group ( , -+ . vs . _+ . ). obiectives : in the newly developed mode of ventilatory support ,,automatic tube compensation" (atc) the ventilator compensates for the flow-dependent pressure drop across the endetracheat tube (ett) thus allowing ,,e]ectronic extubation". the aim of the study is to investigate whether healthy subjects perceive atc in inspiration (atc-in) and in expiration (atc-in-ex) and whether atc provides an increase in subjective comfort compared with the conventional assisted spontaneous breathing mode (asb). methods : healthy volunteers (no preceding lung disease, non-smokers, male, - years)breathed spontaneously through an uncut ett of . mm id via a mouthpiece. the ett was connected with a prototype ventilator evita modified by the manufacturer (drfiger, lebeck) for atc. flow and airway pressure were measured at the outer end of the ett. three ventilatory modes, ( ) asb ( mbarover mbar peep), ( ) atcin, ( ) atc-in-ex were selected in random order. immediately following the transition from one mode to another the volunteers answered by hand sign how they perceived the new mode compared with the preceding mode: ,,better" (+ ), ,,equal" ( ) or ,,worse" (- ). inspiration and expiration were investigated separately by presenting mode transitions (in total; including ,,placebo" transitions). results : the difference between atc and conventional asb is perceived in inspiration and in expiration. atc is positively judged; asb is nega ively judged. the diagrams show mean values _+ sd of five volunteers investigated up to now. the new mode atc is perceived as an increase in subjective comfort. our explanation is that atc preserves the natural breathing pattern better than conventional asb. objectives: to determine the role of cerebral vasoconstriction in the delayed hypoperfusion phase in comatose patients after cardiac arrest. to correlate the results with indices of cerebral oxygenation and the levels of several vasoactive hormones in the jugular bulb. methods: in comatose patients after cardiac arrest we measured the pulsatility index (pi) of the medial cerebral artery by transcranial doppler sonography. the pi is a reliable indicator of cerebral vascular resistance. we also sampled blood from the jugular bulb and measured cerebral oxygen extraction ratio and jugular bulb levels of endothelin, nitrate and cgmp. the first measurement was done within hours after cardiac arrest and repeated , , , , and hours later. results: we studied patients, females, mean age , + , years. the pi decreased s!gnificantly between th~ first and the last measurement from . _+ . to . + . (p = . ). cerebral oxygen extraction ratio decreased also from . + . to . + . (.p = . ). endothelin levels were high, but didn't change during the studied period. nitrate levels varied in a wide range, but didn't change significantly. however, cgmp levels increased significantly from very low levels in the first measurement to very high levels hours later, rasp. . pmol/ml (median; th . - th . ) and . pmol/ml (median; th . - th . ) (p = . ). eighteen and hours after the first measurement we found a strong correlation between pi and cerebral oxygen extraction ratio ( r = . , p = . and r = . , p = . ). we.also found hours after the first measurement a significant correlation between pi and cgmp levels ( r = . , p = . ). we found no correlation between pi and endothelin or nitrate levels. conclusion.~; our results show a high cerebral vascular resistance in the first few hours after cardiac arrest, gradually decreasing during the next hours. this is accompanied by an initially high cerebral oxygen extraction ratio and low cgmp levels, suggesting that the cerebral vascular resistance is induced by active vasoconstriction because of insufficient cgmp levels, leading to a decrease in cerebral blood flow and a compensatory ~ncrease in cerebral oxygen extraction. objectives: sudden cardiac arrest is a major cause of mortality in western countries accounting for over half of all cardiovascular deaths. in most cases the mechanism of death is prolonged cardio-circulatory arrest due to ver:tricular fibrillation (vf) preceding final asystole. recurrent syncopes due to idiopathic vf with good neurological prognosis have been reported in patients with and without cardiac etiology ( , ). in the past measurements of cerebral hemodynamics have been repeatedly done in humans during cpr, but until today no studies of cerebral blood flow velocity (cbfv) have been reported during controlled cardiac arrest in humans not under-going cpr. it was the purpose of our study to evaluate the acute hemodynamic effects of untreated vf on cbfv. methods: after approval by the local university ethics comittee, five male patients aged - years without evidence of cerebral disease were investigated during vf while undergoing implantation of a pacer cardioverter defibrillator system (model d; medtronic| a standard anaesthetic regimen was used (propofol, fentanyl). after implantation of the automated cardiac defibrillator vf was induced by electrical countershock to test effective sensing, pacing, and defibrillation. to measure cerebral blood flow velocities (cbfvmca) the doppler probe was placed above the zygomatic arch between the lateral margin of the orbit and the ear and directed towards the m segment of the middle cerebral artery (mca). results: a total of phases of vf were investigated. duration of vf ranged from to seconds, with cbfvmc a (mean_+sd, cm sec - ) flow pattern changing from pulsatile to laminar flow immediately after onset of vf. conclusions: the underlying mechanism of the laminar cerebral blood flow observed during vf in our patients is uncertain, but it may provide insight into the prognosis of patients with idiopathic vf. theoretically, the laminar cerebral blood flow observed in our pulseless patients may provide a substantial amount of cerebral perfusion even during clinical cardiocirculatory arrest objective: to investigate whether the intensive care nursing staff can inflate more accurately a specific air volume with the laerdal resuscitation bag when they receive feedback after each inflation about the delivered volume compared to no feedback. method: icu nurses were asked to inflate a testlung model times with a specific air volume ( ml, ,ml or ml) under three different conditions (normal, decreased compliance and increased resistance) without and with feedback. we measured the mean absolute difference from the specific airvolume after each ten inflations. results: the largest absolute difference was found when icu nurses inflated ml ( ml). the mean inflated volume for this group was ml. when the icu nurses had to inflate ml the mean absolute volume difference was ml with a mean inflated volume of ml. inflating ml produced an absolute volume difference of ml with an mean inflated volume of ml. the absolute volume difference decreased when the compliance of the testlung was decreased and even more when the resistance of the used endotracheal tube was increased. when the icu nursing staff received volume feedback after each inflation the mean absolute volume difference was reduced between the ml and ml for all specific air volumes. % of the last inflations with feedback were significantly smaller than ml from the specific air volume (p < . ). conclusion: the majority of nurses overinflated the specific air volumes. the largest over inflation occurred when ml and the smallest when inflating ml. when nurses were provided with volume feedback the performed significantly better. we concluded that icu nurses are not able to inflate a specific air volume with the laerdal resuscitation bag without receiving volume feedback. feedback is desirable in order to reduce the volume trauma. objectives: a pro_found impairment in systolic and diastolic myocardial function following successful cardiopulmonary resuscitation (cpr) has been demonstrated by using langerdorff method in rats. in the present study we have investigated post resuscitation myocardial dysfunction in a porcine model of cpr. methods: ventricular fibrillation (vf) was electrically induced by alternating current applied to the ep{cardium of the right ventricle in domestic pigs. following rain of untreated vf, precordial compression and mechanical ventilation was initiated and maintained for min. electrical defibrillation was then attempted and of animals were successfully resuscitated. results: following successful cardiac resuscitation, stroke volume index (svi) decreased from prearrest value of . ml/kg to . ml/kg (p< . ), and left ventricular stroke work index (lvswi) from . to . mmhg,ml/kg (p< . ). both svi and lvswi remained depressed for another hours. these decreases were associated with increases in heart rate from bpm to bpm (p< . ). no significant changes from baseline in mean arterial pressure, mean pulmonary pressure, right atrial pressure and pulmonary artery wedge pressure were observed. prehospital resuscitation efforts c. k ppel. g. fahron, h. lufft, a. kruger, c. th(jrk, f. bertschat, f. martens dept, of nephrology add medical intensive care, virchow-klinikum, humboldt-universit~t, d- bedin, germany obiective: the success rate of prehospital resuscitation in patients with cardiocirculatory arrest in an emergency medical system (ems) may reach - % depending on the time of calling the ems, the distance to cover by the emergency ambulance and the training of the emergency physician and his staff. in the berlin ems, which is associated with the berlin fire brigade, the time between alarm and arrival at the scene ranges from - min, mean min. resuscftation is based on the advanced cardiac life support (acls) according to the guidelines of the american heart association. if resuscitation efforts fail to restore circulation, they are terminated after - min, depending on duration of cardiocirculatory arrest, pre-existing disease, age, absence of an even transient response to cpr. however, there is a lack of practical criteria for termination of cpr in individual decision making. patients: we report cases of prehospital cpr with primary asystolia terminated after - rain of frustraneous cpr efforts including highdose epinephrine and dopamine. results: after termination of cpr, the ecg monitor remained connected and showed permanent asystolia in all patients while the emergency physician completed his records. spontaneous resumption of respiration and circulation was observed in these patients after - min and cpr efforts were immediately resumed, nevertheless, of the patients died at the scene, while could be hospitalized with stable circulation. one of them died hours after admission to the icu, the other survived for weeks in a vegetative state. spontaneous resumption of circulation and respiration is most likely due to the development of extreme hypercapnia and acidosis, which -at least in some patients -seems to be a stronger stimulant of the circulatory and respiratory brainstem centers than cpr with high-dose catecholamines, conclusion: because of the legal and ethical implications of this rare phenomenon, emergency physicians should continue ecg monitoring for at least rain. after termination of cpr efforts. pulmonary artery catheterezation is used for patient's monitoring [ ]. we reported our results on such monitoring in [f.coaobbeb,r.fe enb~-kap~monorm~, ,n ,p. - ] .however not all of the received criteria assessments meet demands that are necessary for early diagnosis of critical states. here we report the data on po ,pco (mm rg),so ,ph levels in femoral [af) and pulmonary (ap) arteries blood, as well as on summary gas pressure (sgp) calculated from pe=(po +pco ) in mm hg in ap blood. these data were derived from:i) subjects free of cardiovascular pathology according to catheterization data during their spontaneous air breathing (n group in ap blood appears to be a measure of adequacy ratio between pc and sgp in ap blood during air breathing; partly its characteristics and variations ranges are presented earlier [ j. in control group it is equal to , • mm hg. tests on sgp neither exclude nor substitute conventional (pc and pco ) tests, but rather include them as a part choosing only additive characteristic -pressure. they appear to be a part of general system of human metabolism regulation by pressure (arterial,venous,intracardiac, tissue,liquor,onco-osmotic,etc ietraabdeminal pressure produces perturbations of cardiac, pulmonary, and renal physiology. this most often occurs fonowing eeliotomy for peritonitis or intestinal obstruction; bowel edema and distention prevent wound closure without unacceptable compromise of blood pressure or pulmonary compliance. a variety of temporizing measures have been reported for managing wounds that cannot be closed: ) using towel clips to reapproximate skin only, )i sewing silastic, marlex or other prosthetic grafts to the fascia to "enlarge" the peritoneal cavity, ) using loosely tied retention sutures for partial closure, ) simply packing the wound without attempts at c~osure. these techniques either traumatize the abdominal wall (complicating definitive closure), expose the bowel to damage, or allow excessive loss of fluid and heat. since we have evolved a suturelees technique which permits the abdomen to be partially closed in a quick, safe, sterile, sealed, atraumatic fashion -while providin! decompression of unphysiologic intraabdominal pressure. methods: whenever possible omentum is interposed between bowel and the open incision. viscera are covered by a layer of sterile, non-reactive plastic, placed deep to the fascia and extending we~t beneath the edges. sump tubes are placed above the plastic and covered in turn by two layers of an adhesive plastic drape which sticks to the skin and seals the wound in all directions, the patients remain intubated and paralyzed. results: we have used this technique in a total of patients, four of whom suffered from compartment syndrome. all of the latter were males and ranged in age from to . all four showed immediate physiologic improvement. all four incisions were eventually closed without complication. one compartment syndrome patient died t days later of multiple organ failure. there were no complications related to the closure technique in any of the patients. conclusions; . selected patients with abdominal compartment syndrome will benefit from decompression using this temporary sutureless technique. the technique a) is quick, safe, sterile, sealed, and atraumatic, b) minimizes loss of fluid and heat, c) facilitates eventual definitive abdomina| closure. although m. brunner m. mitllncr objectives: to determine incidence and predisposing factors for cardiac arrest occurring during the first hours after open heart surgery. methods: the study included patients who, following open heart surgery, had adequate cardiac function and in whom cardiac arrest was not anticipated. all data were prospectively recorded and analyzed. results: from / through / , pts underwent open heart surgery at our hospital. of th~se, pts ( %) (age _+ yrs) had a cardiac arrest during the first hours after transfer to icu. they were operated on for coronary artery bypass grafting (cabg) ( pts), valve replacement (vr) ( pts), cabg and vr ( pts) and aortic aneurysm ( pt). the preoperative ejection fraction was _+ % whereas bypass and aortic cross-clamp time were + and + rain, respectively. prior to arrest, they had a cardiac index of . _+ . l/min/m and were receiving . + inotropes. arrythmias leading to cardiac arrest were ventricular tachycardia/fibrilation ( pts) and bradyarrythmia ( pts). closed-chest cpr was initially performed on all pts and was followed by open-chest cpr in pts. eighteen pts ( %) survived to icu discharge. causes of arrest included perioperative myocardial infarct (t pts, %), tamponade ( pts, %), rupture of the proximal vein gra& anastomosis ( pt, %), graft occlusion ( pts, %); no cause was found in pts ( %). conclusions: postoperative cardiac arrest in stable cardiac surgery pts is relatively infrequent (- % incidence) and is associated with a high survival rate following successful cpr. perioperative myocardial infarct is the most common predisposing factor. group ~deptof anaesthesia and intensive care, semmelweis univ. medical school, buda military hospital intensive care unit, budapest background: when a cardiac arrest occurs in-hospital, the outcome can be improved by a higher quality of basic life support provided by the witnessing health care workers until the code team arrives. this basic life ~pport (bls) should include the best available method for airway management as well. since not all medical staff are ready for carrying out endatracheal intnbation, we investigated the effieacy of the use of different airway management methods during bls. methods: we have investigated the efficacy of airway management of doctors and nurses from different hospital wards: internal medicine, department of surgery, trauma, urology and gynaecolagy. comparing the bag-valve-mask, laryngeal mask and the endotracheal intubafion, we have measured the following parameters: time needs for correct application (sec.), number of incorrect applications (out of ten trial), efficacy of artificial ventilation provided by the device. we used a computerised als trainer manikin for the evaluation of the performance. total performance score was created after the measurement between - . after the first screening we held a x hours training. doctors and nurses were trained for the endotracheal intubation (group it , t ) , doctors and nurses were trained to use the laryngeal mask (group lm , lm ) . all respondent were trained to use the bag-valve-mask device. day, month and month after the training we have carried out retention study using the same method. results: we have found that the efficacy of the artificial ventilation using the above mentioned devices were poor before the training. the average after-training performance scores of the groups are presented in the table below. (bls) should be initiated by the witnessing health care professional. the cpr study introduced a multi level code system, which means bls included sophisticated airway management, early defibrillation and early epinephrine administration provided before the code team arrives. our previous studies confirmed a poor level of cpr performance and a high demand for cpr training among health care professionals. method: we established a cpr training course centre, where doctors and nurses are being trained for in-huspital basic and advanced life support. x hours of training were held. after the theoretical introduction a step-by-step training method ws used for trainees to be familiar with all sequences of basic and advanced life support. then we synthetised all separated sequences. afterwards, a r e play of rescue groups was taken in simulated situations. we also trained the multi level alarm system fur the in-hospital resuscitations. after the training all respondents had to sit for examination. the quality of performance was scored and compared to our previous results. semi-structured interviews were carried out before and aider the training among all respondents to collect information about the course. results: we have found a remarkably high interest among doctors and nurses in our cpr training courses. it was very important to use proper equipment for the training: audio-visual training facilities, computerised als trainer manikin, manual and automatic defibrillator units. the evaluation of the examination held immediately a~er the training course showed a significant higher quality of performance than before the training. the self.-eonfidence of the trainees for initiating and carrying out resuscitation had increased. their overall feeling about the course was positive and % responded the course "very useful". . % of doctors and . % of nurses claimed fur regular training facilities with als trainers, conclusion: the cpr training for health care werkers is mandatory including the training of sophisticated airway management and use of elad~l~ills~tt~r wlaa ~en ~r a~ti~atir ~nel r rm~a'*h*nr m~thnd for training will improve the efficacy, the satisfaction of trainees, therefore their compliance for further co-operation will also increase. s objectives: the effect of reinfusion in emergency surgery and gynecology. methods: we had an experience of autologous blood transfusion in patients whom was produce t an emergency surgical or gynecological interventions in occasion with break tubal pregnancies ( . %), penetrating abdominal wounds with injuries of mesenterial vessels ( . %), injuries of the liver ( . %), blunt abdominal trauma with lien ruption ( . %). in . % patients had the previous somatic pathology. blood loss volume was - ml, & the reihfuside blood volume was - ml, consisting - % of blood loss. it was needn't to fransuse donor blood in . % in further but - ml of contanined erythrocytes were frasfused for supporting of hb concentration on the g/l ( g/dl) rate at the other patients with isovolemie hemodiluttion. results: the arterial blood pressure fast stabilisation on the perfusion level had noted after reinfusion, excluding the case, when the volume of reinfused blood had conisted just % of blood loss at the patient with massive blood loss. complications have noted in two cases. one patient with slash wound, injury of arteria gastrica dextra and total blood loss of ml, has an episode of asystoly, dic (disseminated intravascular coagulation) syndrome, acute renal failure, and acute pancreatitis that we haven't connected to reinfusion. all the complications were successfully corrected and at thirty first day patient with subcapsular wound of the lien that has happened days before complicated with external rupture of the capsull & massive intraabdominal bleeding, has the hemolytical shock, dic syndrome, acute renal failure developed after reinfusion. he was died. all another have no complications. posthemorrhagic anemia had corrected rapidly than in case when hemorrange corrected exclusively by donor blood. conclusions: we consider that simplicity, accessibility, high effectiveness, quite well further results of blood reinfusion, except the case of blood reinfusing that was for time-expired out of blood vessels (more than days in our case) will promote to the wide spreading of this method, especially in emergency surgery, in massive injuries, & in disarters, all the cases of insufficiently of time for selection of lot of donor blood. objectives: study of a reaction of the oardioreepiratory system of pregnant women to i/v microperfusion of clophelinum which is known to eliminate hemodynsmic and endocrine nociceptive reactions and can be used for treating hypertensive syndrome in pregnancy and labor. methods: the following non-invasive methods were used: capnography, spirometry, oxygenography, indirect fick principle based on the circle breathing, plethysmography and integral rheography~ functional indices of cardiorespiratory function were evaluated. results: pregnant women with ~h-gestosis were examined before and after i/v infusion of i ml of . % clophelin solution, . mg/kg/hour. before the treatment intensification of carbohydrate metabolism, hyperventilation with moderate hypooapnia and complete respiratory compensation of metabolic acidosis~ increased alveolar ventilation, decreased alveolar volume, predomination of perfusion over ventilation, hypokinetio type of circulation with dominated load by peripheral vascular resistance to the blood flow was observed in this group of patients. microperfusion of clophelin imp~-oved the ventilation/perfusion ratio, ventilatory and gaseous exchange efficiency, resulted in a decrease of congestion in the pulmonary circulation, possibly owing to a decrease of peripheral vascular resistance by %, of the heart rate by io. %, of the oardial output index by . %. conclusionm: the resulted type of circulation with a decreased load on the heart both by resistance and volume allowed to improve the cardioreepiratory system function in pregnant patients. objectives: the injury severity score is a measure of severity of anatomic injuries. iss is a sum of squares of the highest degrees of the abbreviated injury scale (ais) for each of three most severity injured regions. the purpose of the study is to establish correlation between the iss values and mortality rate in older, polytraumatized patients. methods and results: iss was determined for patients. the mean iss value was . + . while the median value was . minor injuries were present in ( %) patients with iss less than , while ( %) patients with iss more than had severe injuries. increased mortality of the older patients was noted in the range - . all patients older than died while % of patients below yrs of age survived, indicationg correlation between iss and mortality rate in polytraumatized patients above yrs of age. conclusions: this mode of evaluating severity of injuries may help in triage, determining appropriate level of care and as an indicator of future outcome of polytraumatized patients. objectives : tissue hypoxia is a non exclusive cause of hyperlactatemia. other serious medical situations induce hyperlactatemia. therefore, lactatemia could be a non specific indicator of severity in patients admitted in emergency unit. the aims of this study were to examine the correlations between lactatemia with the short term survival course prognosis and the unit of hospitalisation; intensive care unit (icu) or medicine unit, in patients admitted in our emergency department. methods -lactatemia was measured as soon as the admittance, in arterial blood sample of patients which needed arterial blond gas. sixty-one patients were included during months. to assess the statistical performances of lactatemia, sensitivity (se), specificity (sp) and accuracy (ac) were calculated for the threshold determined by the youden's test (se+sp- ). results : fifteen patients were admitted in icu and in a medical unit. fifteen patients died. a group of patients had a lactatemia up to mmol.l" . in this group of patients, had acidocetosis, had asthma, had cerebral vascular ischemia, had neoplasia, had cardiogenic shock, was epileptic, had congestive heart failure, had acute respiratory failure, had septicaemia, had hyperosmolar status finally had medicinal intoxication. lactatemia was significantly higher in non survivor than survivor ( . • vs. . + . , p<o.oool, respectively), the cut point of lactatemia was . mmoll" se was %, sp was % and the accuracy was %. on the other hand lactatemia was higher in patients admitted in icu than in medical unit ( . + . vs. . • p<o. , respectively). conclusions : this preliminary results suggest that lactatemia is a good indicator of the short term survival course in patients admitted in an emergency unit. furthermore, hyperlaotemia is present in several pathology seen in emergency. objective: to determine the pattern of injury, total peripheral white cell, neutrophil, and lymphocyte responses, and the outcome of trauma patients who are leucopaenic on admission to the icu. design: prospective, descriptive study of consecutive admissions over months. setting: a -bed surgical intensive care in a teaching hospital. patients: thirty consecutive adults admitted to the icu following trauma. leucopaenia was defined as a total peripheral white cell count of < x , neulropaenia < x , and lymphopaenia < . x ~ cells per litre. measurement and results: the total peripheral white cell count was documented daily and the neurtophil and lymphocyte counts and differential percentages on days , , and . the incidence of leucopaenia was significanfiy higher in patients with gunshot wounds (p < . ) and hollow visceral intra-abdominal injury (p < . ). eight ( %) patients died. no significant differences were found in the initial mean total white cell, neutrophil, or lymphocyte counts nor in the differential percentages between survivors and non-survivors. the total peripheral white cell count increased significantly in survivors compared to those who died (p < . ) and significant differences were found in absolute neutrophil counts (p < . ) and differential percentages (p < . ) on days and . no significant differences were found in lymphocyte counts or differential percentages. conclusions: there is a signficant association between leucopaenia, neutrepaenia, and intra-abdominal hollow visceral injury and peritoneal contamination. survival is related significantly to resolution of these white cell deficiencies. these findings suggest a possible role of granulocyte colony stimulating factor in the trauma patient with intra-abdominal infection and persistent neutropaenia. amelioration of organization emergency care team in order to improve caring for urgent cases. objectives: emergency care team (ect), as integral part of health, respectively as activity of primary health protection care all acute difficult conditions which vitaly danger patients and distressed. the aim of our investigations was to indicate on the possibilities of amelioration of organization ect in order to improve caring for urgent cases. methods: in our investigations we used epidemiologicai and statistical metods all informations and matherials from terrain ects. results: the number of traumatized in traffic accidents etc. have a epidemic character. it is well known that . % traumatized died in first two hours. ect isn't enough qualified to care a traumatized on the place of accident and during transport. because that medical personnel must have an education with solid qualities. conclusions: . besides a physician specialized (vii --+ vii -~ viii gradus) in urgent medicine, it's necessary to introduce two ( ) medical technicians instead of one as is existing now ( ~ ). .the medical technicians can drive cars and one of them always, drives the ambulance car ("b" category). .the technicians have been specially educated for urgent cases (iv ~ v ~ vi). . such a new team structure should be more capable in professional sense. .we can see an importance of team-work in ects. . such teams should also be more economic in comparison with existing one. . we think, that on the general medical studies need to include a new discipline-urgent medicine! objectives: to detoxicate an organism since we have used biological sorbents: isolated from liver and spleen of human or animal cells or tissue fragments. methods: cellular dialysis ( dialyses) in patients with an acute hepatic insufficiency poisoning by hepatotropic poisons: cc , dichloethane, mushrooms -were conducted using "artificial kidney" apparatus, by means of arteriovenous shunt, formed at forearm with disposable dialyzers. hepatocytes suspension was poured into dializing circuit of dialyzer at - mg of cells per i kg of patients weight. dialysis was performed during - hrs. patients with purulent-septic states were treated as for hemoperfusion through prepared sorptional column: . ml of hemosorbent and . ml of fragmented spleen or hepatocytes suspension with the help of roller pump with the rate of - ml/min, during - min. average volume of hemoperfusion made . . conclusions: in all cases we used both native and cryopreserved biomaterial. analysis of the dynamics of clinical, biochemical, scintigraphic and us-investigastions allows to conclude that application of cellular-sorptional method of detoxication enable to prolong life and reduce lethal outcome in some severe category of patients with endotoxicosis. after infusion of diazepam ( . mg/kg),thiopentone ( mg/ kg) and vecuronium (lmg/kg),patient was intubated and mechanical ventilation was adjusted to mantain normoca= pnia. ct scan showed left parieto-occipital hypodensity with brain swelling. after admission in neurological icu,dexamethasone ( mg/ kg/die),mannitol ( .smg/kg) and diphenylydantoin ( mg/ kg/die) were administred. two hours later neurological status of the patien~ was normal and she was extubated. the risks of stereotactie radiosnkgety are related to: hemorrhgge during the latency interval;transient radia= tion effects;permanent radiatio~einduced complications; radiation induced neoplasia. no epilepsy is reported in pts with avm and no seizure before radiosurgery. in c nclusion, epilepsy can be a posmib~e delayed eompli c~t~n, ~fe~r rgdi surgery for cerebral avm. serum potassium deficiency is a frequently reported finding in the time course of acute myocardial infarction (ami). if this is also correct for patients with ami undergoing primary percutaneous transluminal coronary angioplasty (ptca) is unknown.for that reason we analysed in patients ( m., f., + y.) serum potassium concentrations on ad ,mission and directly after ptca.the reference intervall for potassium in our clinical laboratory is , - , mmol/l. although more than % of the patients with ami undergoing ptca showed normal potassium serum concentrations on admission a measurable decrease of potassium could be found in % of patients ( ) after ptca.therefore for the majority of patients with ami potassium supplementation prior to ptca can be justified to avoid electrolyte disturbances as a possible trigger factor for cardiac arrhythmias in the setting of ami and acute reperfusion due to primary ptca. objectives: diagnostic procedures are very important in the management of abdominal injures in trauma. the aim of this paper is to present our experience with peritoneal lavage as diagnostic procedure in abdominal injury. methods: we analyzed patients to whom peritoneal lavage was applied in the surgical emergency from st of january till st of december . results; in this four years period there were abdominal injures. there were blunt injures. among them in patients peritoneal lavage was applied. results were positive in patients and negative in patients. false positive finding were in patients and false negative in two patients. in patients with positive lavage there were more than , /mm red blood cells, more than , /mm white blood cells and the level of amylase was up to u/i. the gall, urine and stool were positive as well. in patients with negative lavage there were less than , /mm red blood cells, less than /mm white blood ceils and amylase were negative. conclusion: peritoneal lavage is useful and important diagnostic procedure in the management of abdominal injures in trauma. our experience with urgent surgical management of the acute gastric and duodenal bleeding s.se en md, z.milo~evi md, *s.srdi md, k.sar ev md. clinic for abdominal and endocrine surgery, institute for surgery; *clinic for cardiology, institute for cardiovascular diseases; school for medicine novi sad, university of novi sad, yugoslavia objectives: acute gastric and duodenal bleeding are very common complication of gastric and duodenal ulcer. the aim of this paper is to present efficiency of our surgical management of these acute conditions. methods: in this paper results of surgical management of patients with acute gastric and duodenal bleeding, treated in our clinic from the st of january till st of december , are presented. results: among operated patients there were females ( . %) and males ( . %). there were patients ( . %) with gastric bleeding and patients ( . %) with duodenal bleeding. bleeding from gastric ulcer were treated with the following methods: excision of ulcer with suture in patients ( . %), ulcer suture in patients ( . %), billroth i in patients ( . %) and billroth ii in patients ( . %). heinecke-mikulicz-weinberger pyloroplastica was the most frequently used in the treatment of the duodenal ulcer bleeding. bilateral truncal vagotomy was done in patients ( %), duodenotomy with ulcer suture was done in three patients ( . %) and three patients underwent billroth ii operation. we had three complicationsduodenal dehiscence in pyloroplasty. there were no lethal complications. conclusions: based on our own experience we conclude that acute bleeding from gastric and duodenal ulcer can be safely managed with urgent and modern operative techniques. dept. of anaesthesiology. emergency center of serbia, belgrade, srj b ectives and methods: cardiac contusion was evaluated by serial determination of cpk-mb fraction and co using non-invasive doppler technique in patients with blunt trauma of the chest. results: miooardial contusion was diagnosed in ( %) patients, while in ( %) it appeared unaffected. cpk-mb of % and more in comparison to total cpkwas . + , % in patients, and , + , % in pts (p< . ).c of . + . l/min in patients with cardiac contusion, measured hrs after admission at the latest, was significantly lower than in group of patients with co of . + . l/min (p< . ). conclusions: co values were significantly lower in patients with cardiac contusion and correlated with pathological values of cpk-mb fraction. objectives: extracorporal plasmophoresis (pph) was implemented by non-stop method in patients with obstructive jaundice. methods: changes of serotonin (s) and histamine (n) in arterial (ab) and venous (vb) blood were investigated before and after one-time session of pph. s and h in blood serum were determined with fluoremetric method. results: before pph the average s contents in ab and vb did not differ. after one-time pph session s in the blood outflowing lungs was % lower than in the blood inflowing. hours after extracorporal detoxication implemented the indices kept the same level. similar dynamics after pph was observed in h. before the session h contens was equal both in the blood inflowing and in the blood outflowing lunge. after pph h contents in ab was % lower compared to the vb and did not change for hours. conclusions: dynamics of changes of biogene amines shows that under the influence of pph there takes place not only mechanical removal of their surpluses together with plasm, but there sharply grows inactivating role of lungs towards ba substances, which is confirmed by reduction of their concentration in the blood outflowing lungs. this effect is probably connected with the "deplasmation" of the lung cellular elements. simultaneously lungs' cells are freed not only from plasm but from toxic adsorbents on their surface. as a result the lung cells activate absorption of the surplus number of amines from the vessel channel. it is not excluded that s inactivation is due to growing activity of monoaminooxidase resulting in deminishing of intoxication. acute pulmonary embolism: thrombolytic therapy or pulmonary embolectomy? i.lodiena md, phd, s.shevchenko md, pphd., medical university, kharkov, ukraine objectives: pulmonary embolism (pe) remains a challenging problem for diagnosis and management for the emergency physician. the aim of this work is to identify the best treatment for massive pulmonary thromboembolism. methods: during recent years patients with symptomatic acute serious pe were reffered to our observations. selective pulmonary arteriography confirmed this diagnosis in all cases. ( . %) underwent urgent surgery, of them ( . %) with cardiogenic shock and ( . %) with massive pulmonary embolism. patients ( . %) underwent thrombolytic therapy. results: in the patients who received thrombolytic therapy successful results were achieved in cases ( . %), in ( . %) patients subsequent pulmonary embolectomy was performed. mortality rate was ( . %) in the patients who underwent pulmonary embolectomy after unsuccessful thrombolytic therapy and ( %) in the patients with cardiogenic shock and massive pe. lower extremity deep venous thrombosis caused pe in % patients. pe mortality rate is repoted to be %, but all patients with cardiogenic shock and massive pe died. this very high mortality rate related to the clinical status of the patients whose condition became worse despite intensive treatment. conclusions: the results of this study show that in most cases thrombolytic therapy is an effective rapid method of treating pe. however, surgical treatment is preferable when the patients reveal adverse effects to drug therapy, when medical therapy is unsuccessful or when the patients are seriously ill with reccurent cardiac arrest. high-quality pulmonary angiography remains the most accurate and reliable means of diagnosing pe. this prospective study was conducted to investigate the serum thyroid hormone levels in traumatized critical ill patients. serum thyroid stimulating hormene(tsh),total thyroxine(tr ),free thyroxine(ft ),total tri-iodothyronine(tr ),free tri-iodothyronine (ff ) levels were measured within hr.of intensive care unit admission(first day) in multiple tratmmtized male patients(injury severity score higher than ). in fifth day the same hormone levels were repeated. tsh,et ,ft ,tr and ft levels were determined by radioimmueoassay(ria). the levels of 'i~sh,xt ,fr ,et and ft in survivors and nonsurvivors were compared with first and fifth days (table) . in conclusion, we are convinced that there was a high correlation between low ser~n thyroid hormone levels and mortality, serum thyroid hormone levels are prognostic value in traumatized critical ill patients. objectives: glucagon improves myokardium contractility, intensifies kidney blood flow, stops bronchospasm ( ), these were the reasons of investigating its effect on hemodynamics and metabolism in hypovolemic shock expermentally and in clinic. methods : in experiments on white rats with traumatic shock glucagon (novo nordisk) was injected intraperitoneally in dose rocg/kg. patients with hypovolemic shock (trauma, hemorrage) were injected glucagon intravenously in dose mg on the background of infusion therapy. results : glucagon hightened recovery indexes of glucose in rats and patients with shock, whereas in groups without glucagon hyperglycemia developed. rats with glucagon injection had double times urea content than the norm ( , + , mmol& norm - , + , mmol/i ), whereas rats without glucagon had urea content , + , mmol/ ( p < , ). osmolarity of blood plasma in rats having glucagon injections was , + , mosm/kg h , without the drug - , + , mosm/kg h ( p < , ), ldh activity - , + . and , + , ( p < , ) mcmol cec- accordingly. lethality in the group of rats without glucagon was % /n= /, with glucagon - (n = ). in patients with hypovolemic shock in minutes after glucagon administration stroke volume increased to % (sv), miocardium contractility -to % (mc), peripheral resistance of vessels ( vr ) decreased to %. in - , hrs sv increased to %, mc-to %, pvr -decreased to %. conclusion : the study provides the evidence that glucagon has an anti-shock effect, improves hemodynamics and metabolism indexes in cases of hypovolemic shock. reference : picazo j. glucagon in acute medicine : pharmacological, clinical and therapeutic implications (norwell, mass:kluwer publishing, ), p. n, vasina (t) ,n.sebbota hph ( ). dept; of acute endotoxicosis, n.v. s~lifosovslay scientific research institute of ermergency ltealth care, boscow, lk'ussia (i}. institute for problems of cryobiology and cryouledicine of the national academy of sciences of the f/maine, kl'k r-key, [ maine ( ), objectives: the investigation of isolated hepatocytes using's efficacy in patients with acute hepatic fai lln-e. methods: native and crioconsrved allo-and xeno-!mmatocztes fixed on semi;ermeable ~mbr~s were used. results: the artificial supporting system with isolated hepatocttes as metabolic ~its was. ap-plied in patients. during tl~ treatmen~ with this cytotherapz an improvement of clinic state and biochemical rates were observed even inthe first we~s. for instance, the kncreasing of glutamin acid's level in blood up to normal value and decreasing of ammontes -concentration from i ~ mmol/l down to # mol/l were discovered. ~ae diminution of ence,%halo;athy was noted too. general lethality was' equal z, there of i z concerned acute hepatic failure (/k~). conclusions: the using of sum~rting hepatic system is able to cope the ~nenomenon of ~i~. objectives: fat embolism (ee) is an important and insufficiently studied problem of the intensive care medicine. fe is clinically diagnosed in % and morphologically in - % of the victims with severe multiple skeletal injury that is accompanied by the shock. methods: during the last years patients with the cerebropulmonary form of fe were treated in the icu. the prognosis of the probability of fe development was done using the computer system "cite-prognosis" in which the triss-method, dynamic and statistical prognosis of the injury outcome~ and the values of the most severe injury in points were realized. the treatment consisted of the surgical stabilization of the fractures with the authors' design of the rod apparatus in the acute period, long-term mechanical ventilation with peep via tracheostomy, complex fluid therapy using perfluorochemical emulsions (pe), and electrochemically active solution of na hypochlorite (snh) via the central vein. results: the treatment of patients with fe gave a good result that was manifested by the complete regression of psychoneurologic and respiratory disorders. conclusions~taking into account the prognostic data~ it is necessary to provide early complex of intensive care to the polytraumatized patients. it includes the surgical stabilization of fractures, fluid therapy using pe and snh~ early long-term mechanical ventilation. dr. alexandr e. poladko, station of medical aid. kiev ukraine. objectives: the reason of investigation is to prove the necessity of beginning of the intravenous infusion of nitroglycerin before the hospitalisation. methods: from january i to june protocols of treatment myocardial infarction patients in kiev medical aid station. results: the results of treatment are better if infusion began early or prolonged during hospitalisation. conclusions: there were patients with acute myocardial infarction treated before hospital by the cardiological groups. patients were treated with the early infusion of nitroglycerin and without. the results of treatment were: in the group with infusion: mortality in the first hours % the full disappear of pain % in the group without infusions mortality in the first hours % the full disappear of pain % that's why our opinion is that infusion of n. is necessary in the treatment of the patients with myocardial infarction from the first minutes of illness. dr. gennady d. kyrzhner, station of medical aid, kiev, ukraine. object: looking for safe medication which is good for the treatment of arterial hypertension and is simple for use. we inspected the effect of prazosin in the conditions of the cail during the year. method: we used mg prazosin tablets sub lingua and measured blood pressure ones during hours. the parameters were registrated in protocol. result." one hundred patients took part in investigation. the middle age of patients was . the reason of hypertension was not taken into consideration. in two hours after beginning of the treatment we caught the reliable lowering of blood pressure in % of patients. the general condition of patients became better in - min. it was only one accident of complication during the treatment -the orthostatic hypoter~sion, conclusion: prazosin hydrochloride in the dose mg sub lingua is safe and simple for use in the urgent situations. objectives: hypomagnesemia is frequently observed in severely burned patients during the early period after injury. increased urinary excretion is insufficient to explain the magnitude of the magnesium (mg) depletion. the possibility of exudative cutaneous mg losses has been proposed, but not yet demonstrated. the study aimed at measuring the mg content of the cutaneous exudates and urine during the first week after major burns. methods: patients, aged _+ years (mean _+ sd), and burnt _+ % of body surface, were studied from day (d ) to d . serum samples were collected at do, serum and urine from d to d , and on dio, d , d . cutaneous exudates were extracted from the textiles surrounding the patients, collected over h periods from d to d , using bidistilled acidified water. mg supplements ( . to mmol/ h) were prescribed from d to dio according to the severity of hypomg (serum mg < . mmol/i). results: mg serum levels decreased below reference ranges in patients between d and d , and normalised thereafter during supplementation. urinary mg excretion was increased in patients, mean excretion being . _+ . mmol/ h until d . mean daily mg cutaneous losses, were mmol/ h, i.e. mmo; in days. large inter-& intra-patient variability: the daily exudative losses ranged from to mmol/ h. conclusions: the mean daily mg cutaneous losses after burns were larger than the urinary losses, and equivalent to the recommended intakes for mg; the addition of the exudative and urinary losses largely explained the increased mg requirements after burns. complex immunologic alterations occur following thermal injury. the activation and consumption of the complement and dotting systems are suggested to play an important role in the development of the capillary leak syndrome, tn burned patients, a generalized inflammatory reaction as well as the impairment of the host defense are considered to be the major reasons for complications, such as sepsis and multiple organ failure. in a pig model we investigated a possible protective effect of cl-inhibitor (berinert, behring). before conducting the animal experiments the human cl-inhibitor concentrate was analyzed for its inhibitory capacity on purified pig cls and its pharmacoldnetic behaviour in pigs (t / ,id ). pigs received anesthesia and analgesia and arterial, venous and pulmonary (swan ganz) katheters were placed into the carotis and jugular veins. the pigs were scalded for seconds with ~ hot water to achieve a % tbs partial-thickness burn. blood samples were taken prior and after surgery as well as , minutes, , , and every further hours after thermal trauma. two control groups (each n= ) included animals which were either scalded or not scalded and treated only by resuscitation of ringers lactat solution. besides various parameters blood samples were analyzed for complement. the pigs (n= ) received c -inhibitor concentrate at an initial dose of u/kg body weight either immediately or hours after thermal trauma (n- ), followed by three further applications (of reduced amounts) every hours. the clinical outcome as indicated by vital parameters and as well as demonstrated by reduced edema and inflammatory tissue destruction suggested a protective effect of cl-inhibitor. complement analysis revealed a faster recovery of the alternative and classical pathway activities in cl-inhibitor treated pigs as compared to the control group but only if the regulator was given immediately after thermal trauma. from these results a protective function of c -inhibitor on thermal trauma can be assumed. objectives: the aim of study was to characterise the pattern of secretion of interleukin- (il- ) and tumor necrosis factor alpha (tnf alpha) in multiply injured or not injured critically ill patients and to relate these results to their outcome. methods: blood samples of multiply injured ( ( ) ( ) ( ) il- (nis) ( ) ( ) ( ) il- (nin) ( ) ( ) ( ) conclusions: this data suggest tnf alpha is a better prognostic marker in patients with multiple injury, than in critically ill patients without injury. il- is not significantly higher in nonsurvivors of both groups. sepsis is associated with an increased production of nitric oxide (no), as reflected by a rise in plasma levels of nitrites (no ) and nitrates (no ). severe bum injury is associated with similar symptoms of inflammation like hypotension, high cardiac output low vascular resistance and increased vascular permeability so that an increased no production may be involved. the present study included patients admitted to the intensive care unit of the burn center of brussels (age : - years; burned surfaee area - %), and control (non-septic) patients hospitalized in the neurological rehabilitation unit of the erasme hospital (age - years). the patients in both groups were fed enterally with to kcal/kg/day of a standard solution. in the burn group, daring the study period, patients were mechanically ventilated, required vasopressor (dopamine) therapy, and received antibiotics; patients were discharged alive from the intensive care unit, and no patient died during the study period. plasma was sampled for no /no determinations (griess reaction) daily from day to day (n=ll) or to discharge (day , n= ; day , n= ) in the burn group, and once the control group. in the burn group, no /no levels were elevated at day ( _+ #moles/i), reached a maximal value on day ( - p.moles/l) and progressively decreased to day (fig). these values were higher than in the control group ( . :t: . #moles/l, all differences p< . ). however, no correlation was found between the plasma no /no levels and the age of the patient or the total burned surface area; burned patients who became infected tended to have higher plasma no /no levels than those who did not ( + vs - #moles/i, ns). the present study indicates that burn noa/noa (llmol**/l) injury is associated with increasedloo] [__ ] ~ no /no plasma levels, which are ao so consistent with an enhanced no pro- o duction, ao obiectives:urapidil has been recommanded for therapy of hypotension in neurosurgical patients, because it was found not to increase intracranial pressure in patients with compromised intracranial dynamics ( ). in contrast several authors reported an increase of icp after urapidil administration in patients with head injury ( ). our study was designed to determin the influence of urapidil on mean lumbar cerebrospinal fluid pressure (csfp) in awake humans with uncompromised intracranial compliance. methods: after approval by the local university ethics comittee, six volunteers (asa , male, female) were studied in the lateral decubitusposition with the vertebral column positioned horizontally. a gauge needle was inserted into the lumbar subarachnoid space at level l /l and connected to a trancducer (mx | medex inc.) for csfp measurements. the volunteers were advised to keep respiratory rate and etco constant. after a resting period of minutes basline measurements were performed including csfp, cvp, map, hr, etco (cardiocap | datex). then the volunteers were given urapidil . mg/kg over a period of minute. minutes later measurements were repeated. results: statistics: wilcoxon signed rank test, p< . significant; values: mean_+sd, si = mmhg. - _ " _+ * _+ * - _+ " _+ csfp: cerebrospinal fluid pressure, cpp: mean cerebral perfusion pressure. conclusions: during normoventilation urapidil leads to a decrease in map parallel by an increase in csfp and therefore in icp, most likley mediated by an autoregulatory dilatation of cerebral vessels. if this cerebrovascular response is suppressed by hyperventilation, no increase in icp is found despite a uredipil induced drop in map ( ). after longterm hyperventilation cerebralbloodflow is normalized. this might be the reason why the drop in bloodpressure following urapidil administration again led to an increase in icp ( background and objectives: the intestine is one of the most sensitive tissues to ischemia-reperfusion injury. reperfusion of the intestine is often associated with increase in mucosal permeability and ulceration. d(-)-iactate is produced by indigenous bacteria found in the gastrointestinal tract and mammals do not possess the enzyme systems to rapidly metabolize it. the present study was designed to determine the kinetics of plasma d(-)-iactate alteration in rats paused by acute intestinal ischemia-reperfusion injury. methods: following the anesthesia, the superior mesentcric artery (sma) was exposed and it was occluded by a micro-bulldog clamp applied at its origin from the aorta. after min of occlusion, the arterial clamp was removed and the supply area of the sma was allowed to be reperfused ( h). plasma d(-)lactate levels were measured by an enzymatic spectrophotometric assay. the endotoxin content of plasma sample was assayed by the limulus amebocyte lysate test with a kinetic modification of the test kit procedure. results: intestinal ischemia for min resulted in a significant increase in d(-)-lactate levels within the portal vein as compared to sham-operated animals. plasma d(-)-lactate levels had a tendency to further increase after reperfusion up to h. it was showed that significant elevation of endotoxin concentrations in portal vein was alread~r detected at the end of -min ischemia, reaching peak at . h post-reperfusion and decreasing gradually throughout the study period. at the end of ischemia, marked mncosai damaged such as edema, hemorrhage and necrosis was observed. there was evidence of injury to ti, e muscuiaris propria together with diffuse mucosal damage and destruction following reperfusion, particular at h postreperfusion. in addition, penetration of bacteria was commonly found in the intestinal wall at various time points following ischemia/reperfusion injury. conclusions: these data suggest that acute intestinal ischemia is associated with permeability change of mucosal barrier resulting in increased plasma d(-)qactate, which is also remarkably influenced by subsequent reperfusion. plasma d(-)-lactate may be a useful marker of intestinal injury following both ischemia and reperfusion insult. objective: to assess the clinical usefulness of two methods of intracranial pressatre (icp) monitoring: intraparonquimatous recording (icpc) and epidural recording (icpe), versus intraventricular icp (icpv) as a gold standard. we prospectively studied patients with severe head injury (glasgow coma score < ) admitted to our icu between fobmaly and december . icpv was monitored in all pativrats by means of a multipzffolated catheter connected to a water coinnm. six of patients were additionally icpc monitored by a fiber optic transducer (comma r~), and seven of patients were icpe monitored by a couplvd fluid system (plastimedr). icpc was placed homolatetal to the focal, lesion m two cases and contralateral in three; icpe was placed homolateral to the focal lesiou in two cases and contralateral in three. all three systems were calibrated at the ear level. stali~cs: correlation coefficient and lineal regression were done between icpe and icpv, and between icpe and icpv with the hourly p~rs of values obtained dttting assistontial period. results: of the six icpc -icpv studied pa~onts, we observed a correlation coef~cieut r = . (p < . ) with a regres~on line y = . + . x. four of ~hx lcpc -icpv patients had r > . when correlaliou eoet~dent was obtained indixddually. of the seven icpe -]cpv studied patients, we observed a cortelafiau ooeffioiont r = . (p < . ) with a regression line y = . + . x. corralalmu eoetfieiont was inwer than . in all seven patients. corrdation eoelfieients for levals of icpv > man hg, > mm hg and > tuna hg with icpe showed r = . , r = . and r = . respectively; and with icpe r = . , r = . and r = . . the obtained values did not change during the study. conclusdns: in our study icpe was considered a good type of icp monitoring. /cpe signiticantly infravalorates icp values. we observed a good correlatinn between icpc and icpv values in patients with high inttacramal presanre. objective: midazolam is a benzodiazepine agonist widely used for sedation in emergency medicine. few studies in animals and humans point to a direct analgesic effect of midazolam probably mediated by spinal antinociceptive receptors and/or peripheral benzodiazepine receptors ( , ). in our experience in the berlin emergency medical system (unpublished results) with anecdotal cases of extreme chest pain due to binge drinking but no evidence of acute myocardial infarction or extreme abdominal pain due to peritonitis, acute intermittent porphyria, peutz-jeghers syndrome or testicular torsion, we found that small doses of midazolam ( - mg i.v.) were much more effective in relieving pain than repeated administration of high doses of buprenorphine or morphine, which may be associated with a considerable respiratory depressant effect. the dose of midazolam required for pain relief in these patients is non-narcotic and allowed further communication on the character and localization of' the residual pain, which might be very important for the further diagnostic procedure. patients: ten patients with abdominal pain due to acute gastrointestinal bleeding, suspected pancreatitis, suspected acute porphyria, and chest pain with no evidence of acute myocardial infarction received first-line midazolam i.v. at an initial dose of mg and were asked how it affected the intensity and character of pain. results: at the chosen dose of midazolam ( - mg), all patients were responsive to detailed questioning on basic orientation, the character, intensity and localization of the pain, and medical history. none of the patients required an additional opiate. all patients stated that the pain was tolerable after midazolam alone. conclusion: our preliminary clinical observations suggest that low-dose midazolam might be an alternative to opiates in extreme pain of presumably visceral odgin. objectives: it is known that severe head injury in elderly patients is associated with higher mortality than in younger patients. it remains however to be clarified whether the preinjury pathology which is frequent among these patients, affects the outcome. methods: in an attempt to investigate this hypothesis, patients aged over years suffering from head injury, with glasgow coma scale (gcs) of or less, were studied retrospectively. twenty-six patients ( . %) had preinjury pathology i.e. diabetes mellitus, arterial hypertension, heart failure, alcoholism, parkinson's disease etc. (group a) and fifty-three ( . %) did not (group b). the following data were recorded: mortality in the i.c.u., duration of hospitalisation, incidence of infective complications and neurologic status at discharge. results: groups were comparable in terms of mean gcs ( . vs. . ) and median age ( . vs. ). the incidence of brain pathology in the two groups was the following: epidural haematoma . % vs. . %, acute subdural! haematoma . % vs. . %, intracerebral haematoma . % vs. . %, subarachnoid haemorrhage . % vs. . %, diffuse haemorrhage . % vs. . %, contusion . % vs. . % and non-visible pathology (normal ct) . % vs. . %. unilateral pupilary dilatation was found to be . % in group a and , % in group b. the mortality during hospitalisation in the i.c.u. was almost the same: % iu group a and . % in group b patients. however, group a patients had significantly more infective complications, required longer hospitalisation and had lower gcs at discharge. conclusions: the results show that the existence of preinjury pathology does not seem to affect the short-term outcome of elderly patients with severe head injury. it has however an impact on morbidity and perhaps long-term survival of these patients. the assessment of clinical development in intensive care patients with severe head injury still remains a problem. to optimize the monitoring of intracraniel prassure (icp) we rautlr~dly implant an eplduml measuring device in our hospital. the aim of this study was to prove the correlation of the icp-values with ct findings and clinical development. during a month period ( - r the icp was monitored in p~,tients ( male, female) with severe head injury by an eplclural measuring device (epldyn~/$plegelberg| the mean age was . years ( - ). the glasgow coma scale at admission was . ( - ). in all cases the device was placed wfihln the first hours after admission. the tcp was compared with physical examination, radioidglcal or intraoperatlve findings and cunlca! outcome. the average time of measuring was . days ( - ) . the traatment depended on the !cp values recorded. rising icp-valuea ~ed to radlologlcal c ntra!s by ct-scan. in case an intracranlai hemorrhage was detected and drained. the overall survival rate was . %. showed a complete resolutl n, in other . % psychological residuals like decreased mentatlon, in . % sensomotorlc residuals like cerebral nerve dysfunction and aphasia, and . % of the injured remained in a comatous status. in % of our cases the measured values correlated with clinical course and management. in cases ( . %) we observed a displacement of the icp-pevice. there was no icp induced infecllon. istituto di anestesiologia e rianimazione, universit& ,,la sapienza", rome, italy * istituto superiore di sanit& -servizio di epidemiologia e biostatistica, rome, italy objectives: acute renal failure (arf) can be a severe complication of trauma. the current incidence of post-traumatic arf is associated with high mortality . identification of risk factors and prevention of this complication could improve the outcome of trauma patients. methods: one hundred fifty three consecutive trauma patients (age . _+ . , injury severity score . + . ) admitted to icu were studied. incidence of arf was . % ( / ). arf was defined as persisteat plasma creatinine > mg/dl with or without oligoanuria . arf was defined as early when occurring within the first hours (earf) and late when the onset was after the first four days (larf). results: earf occurred in patients while larf developed in patients. age, iss, and incidence of rhabdomyolysis and acute respiratory failure were not different in the two groups. an higher incidence of multiple organ failure (mof) and sepsis ( . % for both) were observed in larf group, when compared to earf ( % and % respectively). abdominal trauma was more frequent in earf group ( % vs %). the gs for earf and larf were respectively _+ . and _+ . while in the group who not developed arf (narf) the gs was . • conclusions: gs score difference seems suggestive and can be that an abnormal cerebral activity (hipofisary hormones?) may play a crucial role on onset of arf in these patients. moreover the frequency of acute respiratory failure in the group of arf was higher ( . versus . ) than narf group. the early ipoxia in the early phase of trauma, then, may be another crucial point for development organ failure. these are preliminary data. a more exact statistical analysis must be perform to have definitive conclusions. to compare the active compression-decompression cardiopulmonary resuscitation (acd-cpr) with the standard cardiopulmonary resuscitation (s-cpr) in out of hospital cardiac arrest patients. is a controlled, randomized study. two groups of patients with cardiac arrest out of the hospitalwere formed. group i, (acd-cpr) and group ii (s-cpr). for the acd-cpr groupweusedthecardiopumpdeviceofambulnternational. asfortherest, the erc ( ) algorithms for acls were followed. the utstein style (for out of hospitat cardiac errest) was used for listing and evaluating all cases of the study. the cpr was contucted by the crew and the doctors of our mobile intensive care units (micu). we studied consequitive patients ( in group i) and ( in .group ii). demographics pre-cpr characteristics (e.g. ecg form of cardiac arrest) and procedures (eg bystanders or second tiers crew cpr, defibrillation, drugs) were quite similar for both groups. the mean arrival time of micu was min. in group i we recorded r.o.s.c. (return of spontaneous circulation) , %, death %, continuation of cpr efforts , %. while in group ii, %, %, and , % respectively (recorded percentage until the admission to the hospital). no significant difference was found in anyofthe short term outcome parameters. no complications related to the acd-cpr technique, were noted. not any significant difference between the two methods was proven (from this small evaluated sample). the results of previous clinical studies are controversial (i) . more sophisticated studies proved the superiority, in a certain number of parameters (e.g pressures, flow, etc) of the new technique although there are many difficulties for establishing clinical results. in the pre-hospital setting that is related to many parameters (speed of the intervention, effectiveness of bystanders cpr, education ofparamedics, etc.)the evaluation is even harder. the superiority ofthe acd-cpr can be proven when it is performed in almost times increased number of studied patients as w~ll as improvement of the technique could lead us to more established results. objectives; infectious morbidity is the major cause of mortality after burn injury, and is due to multiple factors. trace elements (te), which are involved in both humeral and cellular immunity, exhibit severely altered status after burns. te supplementation has been shown to be associated with increased leukocyte counts and shortened hospital stay. the trial aimed at studying the immune responses in severely burnt patients receiving normal te supplies or early large supplements. methods: patients, aged _+ yrs (mean_+sd), with burns covering + % of body surface were studied from day (d ) to d post-injury, were randomised in groups (g): g -control receiving recommended te supplies + placebo; g -receiving in addition large supplements of cu, se and zn from d to d . enteral nutrition was started within hours of injury in all patients. immunological parameters: peripheral leukocyte counts, proliferation of mononuclear cells to mitogens, cell surface molecule expression, and neutrophil chemotaxis at d and d . infectious episodes and micro-organisms were monitored until d . results: the patients' characteristics were similar g & g . the total leukocyte counts were higher in g between d and d , due to increased neutrophils (significant from d to d ). total cd + and cdlg+ cells did not differ, whereas cd + (monocytes) were significantly increased at d . proliferation to mitogens was significantly depressed in all patients. chimiotactism was not altered. the number of infectious episodes was significantly decreased in g with a mean of . _+ . infections during the first days versus . _+ . in the control group (p < . ). conclusions: the large te supplements for days was associated with a significant decrease of the number of infectious episodes. supplementation was associated with increases in total leukocyte, monoeyte and neutrophit numbers. further studies are required to determine the precise mechanism underlying the improved immune defences. objectives: evaluate the efficiency of local adsorption (la) with the use of carbon adsorbents in case of severe burns in expertment and clinic. methods: experimental studies on la were performed on a model of % body surface area iiib-iv burn in rats. a burn eschar was excised on the rd day after burn, the wounds were dressed with the gauze bandages (control) or with adsorptive dressings (la), dressings were regularly changed. clinical investigations were carried out in the course treatment of patients with severe thermal and radiation ilia-iv burn. in the dynamics of bum disease some indices of proteometabolism and intoyacation criteria were evaluated. results: the experiments have demonstrated that the application of la after early excision of a burn eschar exerts a pronounced normalizing effect on a protein electrophoregram and the activity of proteases and their inhibitors in burned tissues preserving vitality. thus, by the th day after burn infliction the activity of cathepsin d in injm'ed muscles is times lower under an adsorptive dressing than under a gauze bandage (control) (p< , ), the activity of trypsin-like proteases is . - . times lower and the antitryptie activity does not differ significantly from the normal level. the cytotoxicity of extracts of burned tissues after the adsorptive dressing application fn vivo and adsorption in vitro is - % and - %, respectively, of the toxicity of control extracts. a similar normalizing effect of la is ok~rved for an intact muscular tissue and blood serum. the dectron-spin-resonance studies have demonstrated that la allows to normalize antitoxic activity of liver and functional activity of kidneys. the application of la in the treatment of patients with severe burns have been shown to localize a region of irreversible tissue changes, accelerate rejection of a burn eschar, attenuate an endogenous intoxication level and, as a result, shorten the time for grafting of a burn wound and accelerate wound heating. conclusions: proceeding from the obtained results, we can consider la as an effective method of localization of a region of irreversible tissue changes as well as of correction of local and general metabolism failures and overcoming burn autointoxication during burn disease. c de deyne, t vandekerckhove*, j. decruyenaere, b. vaganee, v vandewalle*, f colardyn depts of intensive care and neurosurgery*-university hospital gent-belgium. jugular bulb oximetry is the first bedside available cerebral monitoring technique providing an estimation of the adequacy of cerebral perfusion. its routine use in all patients suffering from severe head injury admitted to our ic unit enabled an extensive analysis of all very early cerebral perfusion data in order to evaluate the incidence of abnormal sjo~ data (and their possible causes) in this very eady period after traumatic insult and to search for possible implications as to the emergency management. these very early data were defined as the first hours icu data and icu admission had to occur within h of traumatic insult. over the last years, pts with severe head injury (gcs< ) were monitored by jugular bulb oximetry, starting immediately after their arrival at the icu (mean of . h after trauma, range between - h). in a total of pts (= . %), jugular bulb desaturatiens (< %) were noticed during this early h period. in pts (= %), jugular bulb saturations higher than % were observed, whereas pts (= . %) revealed no abnormal sjo data ( - %) during these first h. concerning the periods with too low jugular bulb saturations (n: ), we found the following correlation ; in pts (= . %) cerebral perfusion pressure (cpp) was below mmng, in pts (= . %) paco~ was below mmhg and finally in pts (= %) we found primary intracranial hypertension. for the high jugular saturations (n: ) we found a primary intracraniaf hypertension in f pts (= %), and a pace level above mmhg in pts (= %). in all patients we could restore jugular bulb saturation within normal range ( - %) with the correct!on of the presumed causative factor. we can conclude that ultra early jugular bulb saturation data revealed a high incidence of abnormal values, with a predominance of jugular bulb desaturations, confirming once again the high incidence of disturbed and too low cerebral perfusion within the first hours after severe head injury. these jugular bulb desaturations were especially correlated to systemic causes, as a too low cpp (caused in the vast majority by primary map insufficiency, and not by intracranial hypertension) and hyperventilation were the major causes of the desaturation periods. as jugular bulb desaturatione are known to be significantly correlated to a worse neurological outcome after severe head injury, one might improve outcome by an emergency management avoiding these possible causes of jugular desaturation. therefore, extreme attention should be paid to the maintenance of an adequate mean arterial blood pressure (above mmhg?) even duhng the few time spent at the emergency department. one should be as attentive to the maintenance of normoventilation during this very early period of admission and hyperventilation without any knowledge of icp or sjo should be abandonned. recently, indomethacine has been proposed for the treatment of therapy refractory intracranial hypertension in pts suffedng from severe head injury ( ). indomethacine, a cyclo-oxygenase inhibitor, gives rise to a significant fall in cerebral blood flow by inducing cerebral vasoconstriction. therefore, its use could result in a drastic lowering of the intraeranial pressure (;cp) in pts suffering from intracranial hypertension secondary to cerebral hyperaemia and in whom the use of other cerebral vasoconstrictive drugs (barbiturates or hyperventilation) appears insufficient to control icp. for the last months, we included the use of indomethacine in our therapeutic flow chart for severe head injury management. pts revealing intracranial hypertension (icp> mmhg) and cerebral hyperaemia (sjo~> %) and in whom icp was not efficiently controlled by the combined use of hyperventilation and barbiturates were given indomethacine in a trial to control icp. a total of head injured pts received treatment for intracranial hypertension over the last months. six of them met the criteria set for the administration of indomethacine. in pts, no decrease in icp or in sjo was observed and both pts died due to therapy refractory intracranial hypertension. in the other pts, a significant fall in icp and in sjo was observed shortly after indomethacine administration. in pts we observed a catastrophic fall of sjo= even below %, indicating an extreme cerebral vasoconstriction with the possible risk of inducing cerebral ischaemia. in one of the pts, icp remained under control without further administration of indomethadne, but he died days later in multiple organ failure. the other pts, needed multiple indomethacine administrations (for pt even during consecutive days) to finally control icp. in all pts, icp was finally controlled, but only pt survived. both other pts died from systemic causes (multiple organ failure in pt, massive gut infarction in the other tat, possibly due to the systemic vasoconsttictive effects of the indomethacine administration). in conclusion, indornethacine might have a role in the treatment of intraoranial hypertension, especially when caused by cerebral hyperaemia. we observed however a poor final outcome and a threatening high incidence of systemic events (multiple organ failure, gut infarction) in those pts receiving indomethacine for icp control. therefore, indomethacine in the treatment of intracranial hypertension should be reevaluated in controlled study settings, before its routine use can be considered. untill recently, intracranial hypertension (ich) in pts suffering from severe head injury was managed in a staircase approach, with csf drainage as first therapeutic step, mannitol as second step, hyperventilation as third step, and finally, barbiturates as the last rescue step for therapy refractory ich. this staircase approach for the treatment of tch was only guided by the intracraniat pressure, and not by other parameters such as e.g. the actual state of cerebral perfusion of the concerned pt. jugular bulb oximetry provides us with the first, bedside and continuous available, estimation of cerebral perfueion. its implementation in a rigourous flow chart, based on as well icp-as jugular bulb oximetry-data might result in an altered strategy for ich management. we adopted a '~ugular bulb saturation (sjo~)-guided approach" for ich management in consecutive pts, suffering from severe head injury (gcs< ). we maintained csf drainage as first therapeutic step, but the decision for the second step was guided by sjo information. pts revealing ich and sjo=values above %, were treated with hyperventilation, and did not receive mannitol. if ich persisted, barbiturates were added as a third step. on the other hand, pts with ich and sjo= vales less than %, received mannitol administration as second step. hyperventilation and/or barbiturates were only added if ich persisted and if no cerebral hypoperfusion was discerned (sjo=> %). our objectives were to prospectively analyze this new therapeuticstrategy, as compared to the formerly used staircase approach of ich. we managed pts with ich, with an overall mortality of . % due to therapy refractory ich. all pts received standard primary care with head elevation, full sedation and normovenfilation. fer pts, csf drainage alone was sufficient to control ice of the remaining pts, pts received mannitol and pts were hyperventilated as second approach. in the third line, pts were managed with barbiturates, with mannitol and pts with hyperventilation. finally, barbiturates were used as the final rescue in pts. these results reveal a less frequent use of mannitol as only pts received mannitol, compared to the pts that would have received mannitol using the former staircase approach. hyperventilalien was used much earlier in the treatment course, as lots were already hyperventilated in the second line approach, were this was formerly exclusively reserved for the third line approach. finally, also barbiturates were used much eadier ( pts received barbiturates as third approach). we may therefore conclude to a important change in the management of ich, induced by a sjo -guided flowchart. however, future studies will have to elucidate if this new strategy for the intensive care management of severe head injury will also result in an improved outcome. obsectives: in a first series of experimental brain injury we investigated the course of brain po , icp and cerebral blood flow after traumatic brain injury (tbi), whilst accordingly there are very few data available and the mechanisms leading to secondary brain damage are poorly understood. methods: in piglets ( days old, , - kg) of either sex we produced a moderate brain injury ( , arm., msec.) using a lateral fluid percussion {fp) device. complete measurements were made before and min. after brain trauma and after , and hours including blood gases, cardiac output (htermodilution), heart rate, eeg, laser doppler flow probe (ldf} and icp values (camino), brain temp., po by a clake type oxygen electrode (licox) and coloured microspheres for regional blood flow. results: immediately after the trauma a typical "cushing"response to the icp peak up to mm hg being highly significant (before mean i mm hg, range - mm hg) could be observed: mean arterial blood pressure rose from appr. mm hg to ii mm hg for - min. in two animals this was followed by an ischemic period lasting min. accordingly icp values gradually returned to starting measures within hours; in the ischemic animals they remained at a level of about mm hg.-no secondary increase of icp could be observed, once icp dropped to starting values within hours. cerebral blood flow (ldf) fell from mean values being i before trauma to appr. zero and recovered to around . brain po started at mean values of mm hg (range - mm hg) and fell to around zero depending upon the severity of the ischemic reaction. on average values of mm hg were reached over the time course. conclusions: with our fp trauma model we can reproduce the well known "cushing"-response after brain injury; secondary icp elevations cannot be achieved, although local edema is observed. direct brain po measurement seems to be a very sensitive variable for detection of cerebral ischemia and anticipates eventually following icp elevations by far. pulmonary aspiration s,traoaras. v. sgountzos, p. agouridakis, m eforakopoulou, e. ioannidou. intensive care unit (tcu) of "kat" hospital, athens, greece ob!e=ives: the reported mortality rate after pulmonary aspiration is variable in several series. the purpose of this study was to find out the influence of preexisting disease or situation on morbidity and mortality of intensive care unit (icu) patients with pulmonary aspiration. methods: patients who were treated in icu and had pulmonary aspiration, were studied, entrance's criteria in the study, all of them obliged, were: ) suction of gastric contents from trachea during intubation, ) presense of a predisposing factor, e.g. coma. ) recent hypoxaemia or new infiltrates in xray. preexisting disease was recorded and correlated with complications and outcome. patients with glasgow coma scale , because of cerebral injury, and patients who died within days from cause other than aspiration, were excluded from the study. method of statistical analysis: chi-square test, results: one hundred forty five patients were studied. the trauma patients were and the non trauma patients . from the trauma patients, had cerebral injury and were polytreumatized without cerebral damage. from the non trauma patients, had malignant neoplasms, neurological diseases in terminal stage, old age, drug overdose, and several diseases. eighty seven from trauma patients ( %) and from non trauma patients ( %) manifested several complications (pneumonia, ards, etc), so there was no statistical difference in complications' frequency between the groups (p> , ). the severity of complications was also proportional in the groups. eighteen deaths were recorded in the trauma patients (mortality %). only deaths correlated directly or indirectly with the aspiration ( %). in non trauma patients, deaths were recorded ( %). twelve deaths were recorded in patients with neoplasms, deaths in patients with neurological diseases, deaths in aged patients, death in drug overdose patients, and death in patients with several diseases, the mortality difference in trauma and non trauma patients was statistically significant (p< , ). in patients with drug overdose the mortality was significantly lower from the other non trauma patients and the difference was statistically significant (p< , ). conclusion: the preexisting disease or situation plays a major role in the outcome of the patients with pulmonary aspiration. the mortality of patients with aspiration seems to be caused by severe preexisting situations rather, that lead to death, than from the pulmonary aspiration per se, which may be a final happening in a predetermined course. obiectives; the purpose of this study was to compare fluconazole and amfotericin-b in the treatment of fungal infections in severe trauma patients. methods: thirty five severe trauma patients who were treated in intensive care unit (icu), were studied prospectively. they all developed fungal infections, prooved with blood positive cultures and at least one of the following: fever, positive urine or bronchial secretions cultures, infiltrates in xrays. the patients were separated randomly in groups. the patients of group a ( patients) received fluconazole rag/day for days. and the patients of group ( patients) amfotericin-b rag/day for also days. compaiison's criteria were the clinical responce to treatment (fever etc), the fungal elimination (blood and other cultures), the relapses of the disease, the side effects of drug, and the outcome of the patients. as method of statistical analysis was used the chi-square test. results: nine patients from of the group a ( %), and from of the group b ( %), presented remission of fever (patients of group b had better clinical responce than patients of group a, and the difference was statistically significant, p< , ). all the patients before treatment had positive for fungi blood cultures. after days of treatment, patients of group a and none of group b had positive cultures. eight patients (from who had positive cultures of bronchial secretions before treatment) of group a. and (from ) of group . had positive cuttures of bronchial secretions after days of treatment, so positive bronchial secretions were fewer in group b than in group a, but this difference wasn't statistically significant, (p< , and p> , ): ten patients (from ) of group a and patients (from ) of group b had positive urine cultures, after days of treatment (positive urine cultures were fewer in group b than in group a and this difference was statistically significant. (p< , ). two patients of group a and none of group b had a relapse of fungal disease. in group a, no side effects were obsepced, while in group b were observed only minor side effects (small increase of serum creatinine in patients, chills and fever during infusion in patients, and hypokalemia in patients). three patients of group a and patient of group b died, because of sepsis. conclusion: amfotericin-b (even i~ short regimen of days), is superior to fluconazole in the clinical and laboratory responce and also in the relapse of fungal disease, fluconazole is superior to amfotericin-b as it has no side effects. ob!ectives: flail chest after thoracic trauma is a serious injury. it is controversial if flail chest by itself orthe concomitant intrathoracic injuries e.g. pulmonary contusion, is the cause of the reported significant morbidity and mortality. in this study we searched the influence of concomitant thoracic injuries in the course and outcome of patients with flail chest. methods: eighty five patients with flail chest after isolated chest injuries were studied, for the purpose of analysis, we separated the patients into groups, patients with isolated flail chest were included in group a, patients with flail chest and hemo-pneumothorax in group b, patients with flail chest and pulmonary contusion in group c, and patients with flail chest and hemo-pneumothorax and pulmonary contusion in group d. complications from the chest, duration of mechanical ventilation and mortality were compared in the groups. statistical comparison of results belween groups was made using chi-square and t-studend tests. results: the patients were . all patients received mechanical ventilation, twenty eight patients were ihcluded in group a, in group b, in group c. and in group d. seventy three patients manifested complications from the chest, especially pulmonary infections. there was no statistical difference among the groups as to number of complications ( twenty four patients had chest complications in group a, in group b, in group c, and in group d. p> , }. the duration of mechanical ventilation was not statistically different among the groups (the mean duration was , days in group a, , in group b, , in group c, and , in group d, p> , ). there was also no statistical difference in mortality among the groups (six patients died in group a. in group b, in group c, and in group d, p> , ). conclusion: flail chest by itself is a serious thoracic damage with many complications, regardless of the presense of other thoracic injuries, which don't contribute to greater morbidity and mortality. the present study investigated the correlation between blood lactate mortality and organ failure in trauma patients admitting between december , and july , in the icu. road traffic accidents were the most common cause of trauma in this studded population. brain damage was the main cause of mortality .nevertheless, of patients died from sepsis and multiple organ failure without significant brain damage and these deaths were potentially preventable. respiratory failure was the most common complication and was developed in ( %) of survivors and in ( %) of non survivors .we noted low fncidence of renal failure may be do to the early and aggressive ittv'asive hemodynamic monitoring and cardiopulmonary support. as part of our routine case protocol serial blood lactate levels were measured in each patient at least times a day until the valses returned within the normal range or until death. we analysed the blood lactate levels on admission, the highest value and the number of days until the first normal value (<l.smeq/i). initial lactate and highest lactate levels were significantly higher in patients with than without organ failure.( . vs . , . vs . meq/l, p< . )the duration of hyperlactemia also was higher in the patients with organ complications. ( . vs . days, p< . ). both initial lactate and highest lactate levels were higher in the non survivors than in the survivors.( . vs . , . vs . meq/l, p< . ) the present study demonstrated that not only the degree but also the duration of hyperlactemia can be related to the development of posttraumatic complications. serial blood lactate measurements are reliable indicators of morbidity and mortality following trauma. s current evidence suggest that peep only affects intracrenisl pressure (zcp)when it interferes with systemic arterial pressure, although the effects of peep over cerebral oxygenation remains unknown. objective: determine the effects of peep over icp and cerebral metabolism measured by sj , kjdo and ceo in severe head injured patients. meterial ~ methgds: patients with glasgow coma scale l at arrival, with difusse brain injury in the first gt, according to marshall criteria,lop and jo monitored, under analgesia and sedation, normoventilated with zeep, without mannitol treatment in the previous hours, normal x ray chest and within the first hours from injury, were considered candidates. peep value where increased fro~ zero to cmh , in three different steps, each one with min of duration. all date were analized on line, pmax p'p ..... p.._, from the ventilator, systemlc haemodynem]c data, cerebra perfuslon pressure (cpp), icp and sjo , in the case of hemodynamic deterioration, during the study, ppc ommhg, extra-volume were administered. if persistence, dopamine were begun or increased dosage. if no good response were obtained, patients were retired from the study. results. patients were candidates, of them were exc;uded due to haemodynamic instability, k total of completed all steps and were e~amined, men and women, age ! . yrs. at hospite; arrival, glasgow were < in patients, and > in the rest . patients mmhg at the beginning. zeep ob/ectives. critically ill patients are transpoded to an intensive care unit(icu), under conditions, which have not been systematically evaluated. therefore, we set suite investigate transportation and admission condition of these patients to our department. methods. we studied patients( females), aged (mean-..+-sd) . _ . yrs, which were consecutively (from august to march ) admitted to the icu, through the greek national emergency transporta~on service. apache ii severity score upon admission was . -+ . (range - ). the following data were evaluated: ) number of medical departments, where health care was provided until final admission to the icu, ) ambulance transportation conditions, ) catheters and tubes inserted before admission, ) vital signs upon admission ) information provided by referring physician (scored on a to scale: history, electrocardiogram, chest x-ray, laboratory data, drug therapy already administered), ) comparison of the state of the patient described by referring physicians, to the actual state u pen admission. resu/ts. one to four medical departments had provided health care before the palient was admitted the icu ( : . %, : . %, : . %, : %). thirty/ ( . %) patients were escorted by a physician. twenty-six/ ( . %) were transported on oxyge n, fio (mean__.sd): -+ %, pao : . -+ . mmhg. five of the remaining , for whom no oxygen was provided, had pao : . -+ mmhg. twelve/ ( . %) were intubated and ventilated during transportation. thirtyfour/ had a peripheral venous line, / had an arterial line, / had a nasogastdc tube, / had a urinary catheter. eleven/ were sedated and / were paralysed. three/ were on inotropes. vital signs upon admission were: arterial blood pressure, systolic . -+ mmhg, diastolic -+ mmhg, heart rate -+ bpm, temperature . -+ cc. patient information score was --. . . the actual state upon admission was found substantially different, as compared to the description of the referring physician, in / ( . %) patients. conclusions. we conclude that several aspects of the greek national emergency transportation service to an icu should be reevaluated and further improved, i. e. ventilatory support, adequacy of information provided and accuracy of prior description of the patient's state. a new perspective must be applied for critically ill patients transportation since . % of the patients were evaluated and treated in more than one, medical departments, mostly primary care, before they were finally admitted to our icu. dclhb is a human derived hemoglobin molecule that has been cross-linked to stabilize and permit heat pasteurization to remove residual proteins and inactivate viruses. dclhb is mixed with a lactated electrolyte solution to yield a total hemoglobin concentration of log/dl objective: to present an overview of four recently completed clinical safety studies of dclhb in the u.s. and europe, and to discuss the properties, actions and potential indications for dclhb. method: patient populations in the four studies included males and females ranging in age from to years. dosing ranged from mglkg to mg/kg. the controlled randomized safety studies were conducted in chronic renal failure patients, surgical patients undergoing total hip replacement or abdominal aorta repair and in hemorrhagic hypovolemic shock patients. these very diverse patient populations allowed safety evaluation of the product in patients who were generally elderly, often hypertensive with some degree of cardiovascular disease, and receiving medications for treatment of other conditions. results: over patients received dclhb in the four:studies. no product related sarious adverse events occurred during the clinical trials. conclusion: results from phase itll safety studies of dclhb in patients undergoing chronic renal dialysis, abdominal aorta repair, or total hip replacement and in patients in hemorrhagic hypovolemic shock, indicate that the product was well tolerated in these distinct populations. although these studies were designed to evaluate safety, the data suggest clinical benefit. follow-up efficacy trials are indicated. prehospital emergency services represent the extension of emergency care into the community and constitutes the manpower, communications, transportations and facilities used to provide care for patients outside hospital. one of the main points of the system is how to decide the hospitalization of patients and what kind of facilities to provide : emergency medical service, fire brigade, locat general praclitionner or ambulance officers. objectives : to realize guidelines for using the prehospital emergency medical service in case of patient'calls outside hospital. methods : from st june to july , all the calls for emergency care were analysed using a questionnaire of items (origin of the call, responses to the questions of an emergency practitionner, kind of emergency service provided and the issue of the patient). after taking account of the appropriatness of the decision, statistical method used was a logistic regression. results : calls were analysed. the criteria, for prehospital emergency medical service using, given by the logistic regression were as following : existence of a call for emergency, thoracic pain, dyspnea, seizures, cyanosis, drug intoxication, fall of the patient, fracture, age, the state of consciousness and the neurologic reactivity. the minimal and maximal predictive values of the model given by the logistic regression are respectively % and %. the performance of the model is %. conclusion : it seems possible to help medical decision of emergency medicine by using only some easy criteria and a predictive model. (italy) objective: to evaluate the incidence of blunt carotideal injury (bci) in patients admitted to our icu after head injury. methods: we reviewed the medical records of all patients diagnosed to have a bci. at admission, the severity of trauma was assessed either with glasgow coma scale (gcs) and with ct scan. bci was demostrated by doppler ultrasography (us) and by angiography (ang). results:since may to april , patients were admitted to our icu with bci ( m, f, age + ). a history of direct trauma was present in patients. admission gcs was in all patients, and was associated with hemiparesis in of them; the last became paretic hours thereafter. two patients had concomitant injuries (a homoiateral clavicular and a controlateral zygomatic fracture, respectively). the initial ct scan was negative in every patient, and showed signs of ischemia after a variable timespan ( - days) after the onset of the symptoms. the bci was diagnosed with us and ang, which demonstrated a thrombosis of the internal carotid artery (ic). in two patients, an intimai dissection was also present. three patients were treated with heparin associated with antiaggregating agents and were discharged alive. the last patient was referred to our icu after the development of a massive hemispheric infarction, and died three days after the admission. at necropsy, the ic thrombosis was associated to an extensive homolateral extra and intracranial venous thrombosis. conclusions:the presence of focal neurological signs despite a negative ct scan should address the diagnosis toward a bci, thus implementing the diagnostic workup with us and/or ang. tab i: distribution of l~tients (%) in the groups the outcome were monitorett results were sabmitted to statistical analysis using a continence table x in z test. res.cl~s: of patients were submitted to thrombolysts and died. the higher incidence of bracb, ar~lhmias (ii degree gg p t e and av block. i degree av block. avsb . <ii. sinus arrest) that requited the insertion of avsc . <cl temporar~ pace-maker was recorded in group a b vs c . ns in % of the cas ~. the rapid recognition of life tab li:;~ test. threatening conditions suggests the monitoring of v r-lead r b' in the course of inferior ami. the authors report their own expirience in application of ringer lact.(rl)and , %nacl/ %dextran . methods:in polytraumatized patients with developed hae morrhagic shock,injures of the chest(qg)and abdomen(q ) prevalid.replacement of the volume loss egan in institutions of general medicine,frequently by rl and dextran or haemaccel.after receiving necessary medical aid,polytraumatized patients wer transported to mma by helicopter,continuing replacing of circulation volume by the same solution. results:average quantities of the solution dministered ~o the injured wer~ - ml.a group of the inoured which,after the admission to mma was resuscitated by adml nistration of the , %nacl/ %dextran @(groupii)( -sml/kg observed to the final surgical management,had statistically higher map(increase of % in relation to admission), cvp(average increase of , cmh~o),diuresis(averagely omi after min.),better gas ~nalyses and acid-base status in relation to the group which was administered only rl(groupi)(increase of the map of q %,average increase c~ of cvp , cmh and average diuresis oml after omin). total quantity of the administered solutions was significantly smaller in the groupii( ml: ml).the only ob served complication was hyperhatr~f~a::and~moderat~hyper osmolerity of plasma which disappeared within hours. the quantity of replaced blodd was considerably smaller in the groupii(qooofnl: ooml).in the group i interstitial pulmonary oedema was observed in two patients(qo%),while: in the group ii no complication was observed.coagulation i disorder and hypotension were not recorded because of the fast infusion of hypertonic/hyperoncotic solution in the groupil as the infusion of , %nacl/ %dextran lasted minutes. w.scherzer(l~,k.lechner( ),r.simon( ). ll)dept.anaesthesiology,trauma hospital,vienna-meidlin !( )neurotraum.rehabilitation center,vienna-meidling both austrian workers'compensation board,vienna,austria what we usually call"unconcious" means only that the patient is not able to interact in any kind of way.experiences in intensive care medicine (robinson, ) ,in general anaesthesia (bennet, ) and with evoked potentials show,that unconcious patients are not automatically unhble to process and recall information.this implicates a challenge to start the efforts to restore the traumatica-!ly desintegrated brain function as early as possible in the acute phase ia (zieger, ) .we present a method to ~repare the patient for the rehabilitation goals of the postacute phase ib,the phase of stabilisation ii and of rehabilitation iii within one concept. to achieve sensory stimulation in phase la we use: attempt at some kind of dialogue by speaking to and tou-ching the patient,to make him experience his body limits, ~acio-oral therapy by ice application,tast and smell pro vocations and trials of feeding,early adaption to circadian rhythm and guiding the patient in every-day-life-ac-tivities e.g.:in the brushing of teeth,washing etc. to achieve motor stimulation and orientation in terms of ~-ace,time and gravity in phase la we use: avoidance of perceptual impairment as produced by air-:sack-beds or habituation to supine position,using method~ according to affolter( ) ,basal stimulation (bienstein, ) , bobath-therapy( ) and facilitation of a physiological moving pattern(pnf)according to knott( ) . conclusions: by integrating all these measures in the ~herapy and nursing even in the acute phase la one prei ares the comatose patient for multisensory stimulation nd motor training and all other rehabilitation activities in the following phases of therapy. s objectives." measurement of cardiac output (co) and stroke volume (sv) requires insertion of a central venous catheter and is associated with a considerable risk for complications. non-invasive methods for determination of hemodynamic parameters have been introduced recently. one of these methods is the aortic modelflow program, which provides co and sv continously using a three-element windkessel model. the aim of the study was to evaluate the accuracy of the aortic modelflow program in critically ill patients. methods: patients (mean age: ) admitted to the emergency department after cardiopuimonary resuscitation (n=ll) and for myocardial infaction (n= ), acute congestive heart failure (n= ) and anaphylactic shock (n=l) were included to the study protocol. after stabilization all patients received a swan-ganz catheter (baxter~; edwards swan-g-anz) via a central vein. co and sv were measured by the use of a cardiac output catheter and injection of rrd ice-cold glucose % non-invasive cardiac output measurement was done by using the continuous cardiac output software package modelflow (tno; portapres| results: overall, paired measurements were used for the evaluation of the accuracy of non-invasive obstained sv and co. mean values, standard deviation and range of co and sv evaluated by invasive and non-invasive methods are summarized in the aortic modelflow provides reliable hemodynamic data in critically ill patients. it may be a useful alternative due to its non-invasive approach and continous measurement. objectives: to determine the feasability and accuracy of a rapid urine screening test (triage tm, merck-diagnostika) in an emergency department. methods: prospective analysis of the triage tm testkit (tt) in patients admitted because of suspected drug abuse during an observational period of months. the tt is a eompetitve immunoassay which gives qualitative results within i minutes for methadone, benzodiazepines, cocaine, amphetamine, opiates, barbiturates and cannabis. urine samples were analysed with the tt and compared to the results of a enzyme-lihked tmmuno-assay (el.a) in our labratory (gold standard). results: during the study patients were enrolled, in of these patients substance abuse was proven by tt and verified by eia. we recorded no false positive or false negative results for benzodiazepines, barbiturates, opiates, cocaine and cannabis. two results were false positive and one false negative for methadone; one result was false negative for amphetamines. the triage-testldt had an overall sensitivity of . and specificity of . . conclusions: the triage tm testkit seems to be a a useful rapid test device in addition to quantitative tests for drugs of abuse in an emergency department. objectives: the purpose of this study was to evaluate the influence of several factors of the renin-angiotensin-aldosterone system on blood pressure response in patients with hypertensive crises. methods: patients with systolic blood pressure > rorohg and diastolic blood pressure > nunllg were included into the study. prior to treatment blood samples for determination of plasma renin activity (pra), angiotensin converting enzyme (ace), angiotensin ii (ang ii) and aldosterone (aldo) were collected. all patients received rog enalaprilat intravenously. success of treatroent was defined as a reduction of systolic blood pressure below mmi-ig and diastolic blood pressure below mmi-ig within minutes after start of treatment. results: patients were included in our study, ( %) patients responded successfully to treatment. mean arterial pressure decreased in responders by . mmhg and in non-respenders by . mmhg (p< . ). responders and non-respenders differed signii'icantly concerning pra (p= . ), ace (p= . ) and ang ii (p= . ). . . the extent of blood pressure reduction correlated positively with the pretreatment pra and ang ii concentrations (correlation coefficient for pra: r= . ; ang ii: r= . ). conclusion: our data confirm that in patients with hypertensive crises blood pressure response to ace inhibition is mainly determined by circulatory pra, ace and ang ii. as the extent of blood pressure reduction correlates with pra, ace-inhibitors in patients with suspected high renin status cannot be recommended, as excessive blood pressure reduction, which carries a considerable risk for further organ damage, may occur. f. staikowsky, n. grillon, f.pevirieri, c.jedrecy, c. zanker, f. michard, a. haft medical emergency department. hospital bichat, paris epidemiology of acute intentional self medications-poisoning (smp) in france is especially known by data of poison control centei,s and intensive care units (icu). the purpose of this study is pro~,ided characteristics of this problem in a med for adults. method: july to june , files of patients consulting to the ed for smp have been retrospectively analyzed. results: patients, women and men, . + years old (range - ) have been admitted for episodes of smp ( % of all consultations) whose relapses during the period of study. psychiatric disorders, drug addiction or hiv patients was found for respectively . %, . % and , % of patients. the interval of time between the ingestion and emergency consultation was noted for % of smp ( + min, ranges - ). the involved products name was known in totality in % of cases with an average number by episode of . + drugs (ranges - ). the most often, ( %) or ( %) different products were interfered. the nonbarbiturate psychotropic drugs accounted for . % of the products (benzodiazepines %, antidepressants . %, neuroleptics %, carbamates . %, imidazopyridines . %, cyclqpyrrol nes . %). analgesics and nonsteroidal antiinflammatories represented . % of all drugs, anticonvulsants . %, cardiovascular drugs %, antiinfective agents . %, drugs against cough . %, muscle relaxants . % and antihistamines h . %. the benzodiaz pines were present in episodes, alone in episodes. in . % of cases, there was a simultaneous intoxication with alcohol. the processing consisted of gastric lavage in . % of cases, activated charcoal in . % of cases, flumazenil in . % of cases, naloxone and acetylcysteine in . % of cases; orotracheal intubation was performed in patients. admission in hospital was effective for patients, in medical ward (n = ), psychiatry (n = ) or icu (n = ); no fatal case was recorded. conelusion: smp to ed are often benign. the benzodiaz pines are the most often incriminated but the new anxiolytics and hypnotics (imidazopyridines and cyclopyrrolones) take a growing place. the latsion burn center of athens. its planning constructive and functional refinements j. ioannovich, a. petalas-vourekus, d~ serbetis, h. carsin a bed burns unit is under construction following a donation to the general hospital of athens. the plan of the unit, covering a surface of approximately . m is based on the principle of three identical bed satelites which may function totally independent from each other. in the center of the unit the common facilities are installed, like operation theatres, storage rooms etc. this new modification in the plan of a burn unit is presented in this paper. the advantages from the fucntional, administrative and medical point of view are discussed. tiffs anisotropic conduodon could favour the ocenrence of a circular movement of the impulse that leads to tachyeardias by reentry. purposes of this work were to study, with the help of epicardial mapping, the influence of a trieyclie antidepressant, clomipramine (c), on the conduction velocity longitudinal (vl) and transverse (vt) to myocardial fiber orientation and on anisotropy (a = ratio vl/vt), and their modificutions by the sodium bicarbonate ( ). method: a plaque of electrodes, positioned on the left anterior ventricular wall of anesthetized dogs, allowed to deliver, thanks to central electrodes, programmed electrical stimulations inducing vcuttienlar complexes, and to collect them. each entailed unipolar dectrogram was processed by a computer system that drew the isochrones and a map of activation allowing the calculation of v. the c was infused ( . mg/kg/min iv) during rain; at t , dogs received the b until the retuni of qrs to its initial value fro). a lengthening of qrs of at least % of its value at to was demanded before the administration of b. results: dog was excluded because of an.~nsufficient prolongation of qrs before the administration of b. all values (map : mean arterial pressure, i-ir : heart rate, qrs andqt intervals, v) differed significatively ( < . ) compared to values control fro)except qrs at t . the b ( + ml/kg; ranges . and . ml/kg) modified no studied dements outside of the ( }rs. to ti t t t t t a , + , , + , , + , , + , , + , , + , , +- ,~ conclusion : the c slowed v l and v t without modify the anisotropy. the b did not modify the v of~conduction while the qrs prolongation was corrected. the c acts as a class i antiarrythmie drug on the inward sodium current during the phase of action potential; the gap junctions have shown to be important in the conduction and an action on the gap junctions such as a modulation of the junctional resistivity, can not be rule out. is the doctor a heroe ? p. t.schies~.he, t. bauer, m. seyr dept. of anaesthesiology and intensive care, aokh krems, austria objectives: helicopter emergency services (hes) are getting popular more and more. the results concerning outcome are encouraging. however, some recent accidents with dead or badly wounded hescrew-members have shown the relatively high risk for the crews. therefore we were interested to eval ate the motivation of physicians to participate in a hes. this survey was designed to investigate current concerns about safety and motivation of doctors on emergency call. methods: a questionnaire was sent to doctors of the austrian emergency system. the survey consisted of multiple choice questions and subjective scoring tables from (--full agreement) to (=disagreement). overall, "/. of the active emergency physicians participated in the survey. results: . % of the doctors assume the system is basically safe, experienced doctors tended to have less trust in safety. only % would not hesitate to go into action by dark. . % stdctly refuse night flights to accidents outdoors. although defibrillations are assumed to be safe dudng flight, only % would do it. . % of the doctors would rather stop flying. the most common reasons for ,uitting were wish of family and fear of an accident. . % conclusioq: short transportation times help to avoid trauma related stress, pain and shock-induced organ complications. therefore the physiologic and economic advantages of hes are undebatable. however, the survey data indicate a considerable concern about safety of the medical personal in a hes. crash landings within less than years with deadcases and badly wounded crew members in a small country like austda make desire for safe flying conditions understandable. obiectives: to evaluate the clinical usefulness of trachlight. methods: trachlight is a new device facilitating endotracheal intubation. a stylet with a lightprobe is inserted into the endotracheal tube. intubation is guided by the light glowing through the neck tissues, thus rendering direct laryngoscopy unnecessary. intubation using trachlight was studied in patients (age - years). the indication for intubation was elective surgery in patients (asa i-ii) and emergency intubation in patients. in the elective patients, anaesthesia was induced with thiopentone supplemented with fentanyl, and intubation was facilitated with vecuronium. the cause for intubation in the emergency patients was dyspnea in , cardiac arrest in , trauma in, and unconsciousness due to drug overdose or seizures in patients. intubation was facilitated with medication in patients. results: of the elective patients, ( %) were successfully intubated. six patients ( %) needed two attempts before successful intubation. the duration of intubation exceeded seconds in patients ( %). of the emergency patients, ( %) were successfully intubated. six patients ( %) needed two attempts, and the duration of intubation was more than seconds in patients ( %). in % of all patients, intubation was assessed as easy. no or insufficient glow, prolonging intubation or necessitating two attempts, was noted in patients ( %). oesophageal intubation occurred in patients. conclusions: trachlight may be a valuable adjunct for intubation in varoius settings provided that adequate training is provided. a learning curve was found to exist. objectives: to compare enoxaparin and standard heparin in cavhd and calculate the value of laboratory controls in the treaanent. patients and methods: twenty patients needing dialysis for acute renal failure participated in the study. the main exclusion criteria were massive bleeding or a thrombocyte level < x e /i. in each treatment the same type (av- , fresenius ag, germany) of a polysulfone capillary haemofilter was used. the study scheme consisted of two consecutive four-day cavhd treatments, one course for each type of heparin. the order of heparin administration was counterbalanced between patients. the standard heparin was given as a continuous infusion aiming at an activated coagulation time between and s. the initial enoxaparin dose was rag every :th hour intravenously, but was modified by any signs of coagulation in the dialysis blood lines or bleeding complications. results: the dialysis treatment was adequate in both treatment modes, with mean blood urea levels . and . mmol/l respectively (ns). the bleeding complications were moderate and similar in both treatment modes. the mean life-span of haemofilter using enoxaparin as an anticoagulant was some longer than using heparin ( . + . h versus . + h, ns). the mean aptt-levcl during heparin treatment was s and during enoxaparin treatment s (ref. - s). the mean daily dose of heparin was nag, that of enoxaparin lg mg. the mean anti-xa activities were . u/mi and . u/mi, respectively, reflecting a better bioavallability of enoxaparin. conclusions: both anticoagniation modes were equally effective and well tolerated. the amount of enoxaparin needed for a proper anticoagulation was, however, less than half of that of standard heparin. the changes in aptt level were too slight to make its use possible in controliing the dose of enoxaparin. the use of enoxaparin seems to be rather safe in cavhd even without laboratory controls. the adv~ucea in the management of computerized data of an intensive care unit have been petalled to the clinical advauces and the increasing sophistication of methods of diagnosis fop the clinical application an therapy. this has led our unit to design and develop a computational system called timbu which is used to help physicians assist patients. among its various uses, this system has a software for the hemodynsmic control of a critic patient. this program was carried out to get as fast as possible the hemodynamic data of the patients in an intensive care unit. as an example, we can mention that when we load data obtained through direct measurement from the monitors and the lab, the program calculates parameters that guide, intelligently, to the diagnosis and therapeutic behaviour of the hemodynamic problem through screen messages. the validation of this program in the unit of intensive care has demonstrated that its use allows a more efficient handling of the patient with serious hemodynamics and respiratory disorders. ohieetlve: traema is a heterogeneotm 'disease' that ecatr~ a~"o~s all age ~oupe with v~ying degrees of severity. this imerogeneity has made the di~e, trmma, diflkaflt to r the ehn of this stady wa~ to assr the fitaen of saps in ibis popeleties. methode: in order to compute the ~ probability, a model derived from logistic regression w~ developed. meam'e of calibration (goodaess-of-fit stetislj.r and di~'riminafion (roc ou~e) were adopted in developmm~ and validetlon set randomly taken from a database of pts eeeseemivety admitted in icu (arohidia). ~ witho= salm, p~ yom~ am is yam, with los ~horter thma hotam wore exr fa'om thi~ mmly~ir thi~ model v~s then evahmed on the ~per ~mbgro~ (i.e., trmma pts). if'it did t~t fit the data well ~, new model wm developed rer the logit only on trm=~apm. reims: data were availabte for pts during aperiod of three .y~m , treama pts were . %), teats of calibration iadioaled probability model did mot provide m adequate refle~on of the mortality ezperieace in pm with ireutae, being the observed mortality lower flma the expected (figm'o). a aew model was then variable. this oastomized model fit~ the de~t of trmara pts very well (g =- a p> . ; roc = , ). the di:lferencea between the two modele were evident. conclusion: this ltudy shows that mortality in iramna pts is over wcfe~d when ~se~ed by menm of saps. however the r mode! meets high standmcd in terms of calibration mid dil~'iminat'~o~ ']"he advaatage of ~imd models meaas the colleotion of the ~ set of variables for all pm admitted in icu e~einat the ase of diasma specific ~oring syatex~. ("sl"): effects on cardiovascular and hemostasis systems (cvs, hss) a.oborin~ph, ~.~yndiuk~ph, b.kondratsky ~pt. of'""su~gery and transfusiology, research institute of hematology, lvov, ukraine objectives: great interest has been shown recently in the use of hoss for the initial resuscitation of hypovolemic shock. methods: the study was carried out in dogs -~h hs was induced by jet momentary hemorrhage (h) from a. femoralls (the bloodloss volume made . + . ml/kg). the treatment was begun after .u+o. hrs of h. "sl", created on the basis of-sorblt and natrium lactate ( mosm/l) was injected into v. femofalls at the dose of io. ml/kg. results: it is established that before treatmen-~rterial blood and central venous pressures (abp, cvp) diminished to . mm hg and - . + . cm h (p .o ), while heart rate (hr)-increased to . + . per min (p<.o ). by this the indices of ~latelet counts (pic) and plasma fibrinogen (pf) lowered by . % (p<.i) and . % (p~. ), while fibrin degradation products (fdp) enlarged by . % (p~ . ). after - min of treatment termination abp and cvp increased to . + . mmhg and . +o. cm h (p<.o ), and ~[r diminished to t . + . per min (p>. ). at the same time the indtces of pic and pf enlarged by . % and . % (p>.i), while fdp diminished by . % (p>.i). one of dogs survived. life duration of the other dogs was . + . hrs. conclusions: the obtained data are ~he evidence of normalizing influence of "sl" on cvs and hss, and allow to recommend it as a mean of initial resuscitation of hs in clinic. oblectives: we prospectively studied icu patients with severe head injury (hi), which cerebral lesions monitorized with sjo through opljcal fiber and the cerebral flux with tcd. methods: since january until june , we collected ht admitted to the icu, and of them monitorized with optical fiber in the right jugular bulb and tcd. all patients needed mechanical ventilation related to gcs <__ , with ct in admission (classifing lesions according to marshall and al.) . we related the final results to the evolution of sjo and tcd, with other monitorizing methods like gcs, ct and icp. ~sults: conclusions: in patients with gcs _< , sjo is useful to evaluate the evolution towards vegetative state, still more in cases with ct type ii in admission and higher apache ill. elevation of icp implies an evolutive nsk to brain death and data of tcd is a good indicator of brain death, the complete monitorization of these patients can improve the therapeutic control of this neurologic problem, , ( m, f) , (m. age: + years), divided in two groups (a and b) under specific criteria(tremor and/or fever during admission in i.c.u., or not). the injury severity score was > in all studied patients. tbe group a ( m, ") had no tremor and/or fever on admisskm, while em group b (tin, the above criteria were ix)sitive. bhx~d samplings were taken - hours after accident and - rain. after admisskm in i.c.u. micro-eli~ method was used for measuring cytokinc-levcls. statistic analysis was performed by studcnt-t test. as control group, healthy people were examined. _resu!_ts-il-lct, il-ii~, il- and tnf-tt levels were similar to control group levels in both groups a and b. i!,- and g-csf levels were found increased in both groups (p< jxjl), while il- levels were statistically significant comparing to group a. in con_tin_skin, during immediate post raumatic period,proinflamatory cylokines il-i~, il-i~ and tnf.-ct, produced in an earlier stage than ,. , cannot be detected,whereas .- was increased significantly, especially in group b. g-csf was fimnd in increawal levels in both gr(mps, without statistically significant difference between gnmps a and i|. objectives-l~valantc proteolitic activity, disorders in" eariy, period after combined trauma and p(~.ssibilit, i' of their correction by injection of proteo[ysis inhibitors contrycal and s-fto~:nracil in combination with driving an isotonic snlu~ion of sodlum chloride and polig[ucine. methods: biochemicai studies of proteolitic activity in dogs with limited deep burn and acute bloodloss, . result:s: in case of deep % burn, cornplicated by bloodshed the of blood grows at - times. it; is the restdt of the pancreas glandischemi demage, caused by the centralised circulation of blood and intensifies the deviations of haemodiaamics and albumin exchange. the degree of endogene intoxication by mean mofecular peptides which are the products of albumin decay reses to %, and % in hours. in hours after the trauma the-process is accompanied b ! , % lower inhibitory activity of blood, where as at the peak of the trauma it was , ~ higher. that proves the nnfavuurahle process of the shock in case a combined trauma. conclusion: the vein injection of 'proteolysis inhihitotz cnntrycal and -fforuraei[ in cumbination with driving an isotonic solution of sodium chloride and p.dligh]cine to refill lhe loss of blood helps to lower at times the profeolitic activity of blood. but it still remains above the initial level. the degree of endogene intoxication lowers at times; [ emodinamics aml albumin exchange stahilised. objectives: nimodipine, a known calcium antagonist, has been shown to dispose a beneficial effect on patients with subarachnoid hemorrhage, but its efficacy on traumatic or spontaneous intracerebral hematoma has not been justified. therefore, we studied the effect of nimodipine on the histopathological changes following an experimental intracerebral haematoma in rabbits. methods: twenty-three new zealand albin rabbits of both sexes, weighing - , kgr and at age of - months were anesthetized and a small burr hold in the left parietal aerea was carried out under aseptic conditions. the dura was opened and . ml (this volume assuring a normal incranial pressure after kaufman ) of autologous blood was injected into a depth of mm via a needle of . mm bore. the wound was closed and the animals were left to recover. nimodipine, of , mg/kgr of by weight per day was given via a nasogastric tube to fifteen animals for a period of time of fifteen days (group b). six rabbits were given water and served as control (group a). both groups of animals weie sacrified on the fifteenth day, their brains were removed and immersed into % formalin solution. tissue sections of ~ were embedded into paraphin and stained with haematoxyline and eosin, mason and gfap stain for gliac cells. results: two animals died after the surgical procedure, because they developed large intracerebral bematoma. no animal developed neurological deficit except one of group a which manifested a right side hemiparesis. the results of the bistopathological changes are the following: i) the mean -+ sd diameter of the lesions in the group a was --. ~t while that of group b was + ~t (p< , ) ii) secondary ischaemic neural tissue changes, characterized by the extravasatlon of red cells, the presence of haemosiderin-containing macrophages and signs of low grade inflammation zpredominated in the specimens of group a and were totaly absent from those of group b. iii) a ring of gliac hyperplasia and a low grade local fibrosis was found, encircling the lesions in the specimens of group a in contrast to those of group b. conclusions: nimodipine when administered in rabbits following the development of a non increasing the icp experimental intracerebral haematoma, prevents the extention and the severity of the lesion. objectives: to study the efficacy and side effects of adding intramuscular clonidine (clophelinum) to analgesic regimen in early management of patients with serious burn injury. methods: pts with - % bsa second to third degree flame burns (respiratory tact injury excluded) to yrs of age were randomised to study (n= ) and control (n= ) groups. burn shock was treated with hypertonic saline -bicarbonate solutions ( mmol/l na +) ml/kg/%bsa for the first hours and ml/kg/%bsa for second day. analgesia in control group for the first hours was provided by regular hourly intramuscular administration of mg of morphine sulphate and mg of analgesic -antipyretic analgin with mg of diphenhydramine (dimedrol). from the rd day regular administration of morphine was finished. in the study group ixg of clonidine was added -hourly for hours and dose of morphine halved. vas, verbal rating scale for sedation (vrs, - ), sleeping time, spo , hr, bp, diuresis, vomiting and other complications were comparatively evaluated during patients' stay in icu. results: addition of ~g of intramuscular clonidine daily allowed to achieve better analgesia and sedation with halved consumption of morphine. mean vrs in study group for the first days was . - . vs . - . in control group with twice longer sleeping time. there was significantly less tachycardia in study group; dynamics of bp for the first hours did not differ considerably; later, there, was tendency for hypotension in study group without adverse effects on diuresis or other indices of tissue perfusion. because of high incidence of chronic ethanol abuse among study population pts of control group suffered from psychomotor agitation or delirium, probably as a sign of alcohol withdrawal syndrome (aws). this made regular evaluation of vas impossible. in the study group only pt showed sign of aws. mean vas score was in . - . range for first postburn days. pts appeared excessively drowsy due to clonidine, but it had no adverse effect on their overall clinical course. mean spo values in study group were in - % range, among controls - %; vomiting was absent in. cionidine group vs cases among controls conclusions: clonidine could be a valuable addition to analgesic -sedative regimen in burns, especially for prevention of aws and deserves further study in this regard. hemodialysis -hemoflltration modifications and/or intratracheal gas insuflation have been recently used for blood gas exchange in several models of respiratory failure. objectives: evaluate the combination of cavh-m and igi for respiratory support in experimental acute lung injury. methods: five mongrel dogs ( -+ kgr) were mechanically ventilated inroom air, paralysed, heparinized, connected with a cavh-m system (diafilter- polysulphone membrane) and remained stable for one hour (pao~= . • peco = -+ mmhg, ph= . -+ . , bp= -+ mmhg and pap= -+ mmhg). all was induced two hours after oleic acid infusion ( . ml/kgr) into the pulmonary artery (poo~= . _+ -p< . , paco~- . _+ -p< . , ph= . -+ . -p< . , bp= -+ -p=ns, and pap= _+ -p< . ). fio % for the next minutes did not significantly altered the b ood gas abnormalities. afterwards, pure oxygen applied simultaneously a) through the inlet of the filtrate's compartment of the hemofilter ( l/min) while filtrate and gas were removed from the outlet port (bypass flow ml/min) b) through a thin intratracheal catheter positioned cm above the carina ( l/min). the fio given through the ventilator readjusted to %. results replacement fluids/filtrate during the next four hours were not exceed . l/hour, whilst the blood gases and pressures were improved as follow: cavh-inlet:pao.= . objective. to compare the changes in humoral immunity in trauma patients following massive transfusion of autologous and homologous blood. methods. we studied randomised clinical groups of patients each containing patients with trauma and operation of large arterial vessels. the amount of autologous or homologous blood transfused to the patients was exceeding ml, while the patients in the control group did not recieve blood or blood products. results. we recorded most pronounced and characteristic changes on the -st and on the -th day in the group of patients recieving homologous blood transfusion, i.e. decreased amount of igg,iga,igm,c and c fractions of the complement system, haptoglobin and significant and sustained rise of circulating immune complexes up to the end of the study period. in the control group of patients the decrease was weaker and lasted only during the -st post-operative day; the dynamics of the circulating immune complexes level were almost the same as in the first group of patients. in the group of patients recieving autologous blood transfusion, the parameter values did not change significantly from preexisting levels after the -st day, while on the -th and on the -th day showed a tendency towards aslight rise. conclusions. autologous blood has a favourable effect upon humoral immunity and should be the transfusion medium of choice in cases where autologous blood reinfusion is technically possible. ivan petkov, m.d., rumen farashev, m.d. and dimitar terziiski, m. d. medicine, military medical academy, g. sofiiski str., sofia, bulgaria objective. the amount of blood lost during trauma and operation could hardly be forseen and donor blood supplies are not always available in sufficient amounts. rare blood group types and/or unexpected haemorrhage pose a great challenge to the transfusion therapy and the methods of intraoperative autologous blood transfusion. methods. we report a case of a -year old male patient with extremely massive intraabdominal haemorrhage ( m( blood loss ) during an abdominal aorta reconstruction following a traumatic injury of the abdominal aorta. we achieved a successful reinfusion of ml of autologous blood using an original autotransfusion system developed by us ( pat. no / . . ) . results and conclusions. the autotogous blood in the case reported here was the only and the most suitable transfusion medium for the rapid intraoperative compensation of the acute haemorrhage and the favourable outcome of the patient. the post-operative period was smooth and no significant disorders in the clinical course as well as in the laboratory tests ( morphological,biochemical,coagulation and immunological) were recorded. there were no complications during the postoperative period despite the fact that the amount of blood reinfused to the patient was slightly exceeding his own volume of circulating blood. objective. the haemoglobin concentration and the perfusion pressure value could not be the only criteria for the early signs of tissue and organ dysfunction. because of this, we employed the extensive monitoring of oxygen transport during severe trauma in order to. achieve dynamic evaluation of physiologic compensatory mechanisms and to assess the efficacy of intensive care management. methods. we conducted a prospective controlled trial on the blood oxygenation, oxygen transport and tissue perfusion during the first days after the trauma in patients with polytrauma. we used a swan -ganz pulmonary artery catheter (beckton -dickinson, u.s.a.), deseret cardiac output computer (medical inc., u.s.a.) and hewlett -packard monitor (hewlett -packard, germany) to measure and calculate all the parameter values. the severity of the injury was assessed using the apache ii score system. all the patients had scores over . results. the results show a significant decrease in the arterial blood oxygen content and in the arterio-venous difference, as well as an increase in alveolo-arterial oxygen difference and in the transpulmonary right-to-left shunt. the tissue oxygen supply and the tissue oxygen consumption reveal a tendency towards a decrease below the physiologic minimum of adeqate values. the erythrocyte current velocity and the ratio between oxygen transport and erythrocyte current velocity also decrease inspite of the optimal blood rheology. conclusions. the dynamics in the parameters values are most pronounced between the -nd and the -th hr after trauma, which predisposes patients to the risk of developing stable hypoxemia and characterizes this period as the most critical for tissue metabolism and organ dysfunction. posttraumatic changes in immune mechanisms in lung compartment in trauma were analyzed in ao and da inbred strains of rats which differ in their immunological reactivity: the former being low responder and lat-~er hiperresponsive. methods: the levels of tnf-alpha activity in the supernatants of cultured lung lobes and dynamics of cells migration from tissue explants in h lung cultures were assessed in ao and da rats subject ted to severe burn trauma. results: increased levels of tnf activity ( + pg/ml compared to + . pg/ml in control) were found od day following trauma in lung sups of ao rats while no changes in the levels of activity of this cytokine were found in lung-sups od da rats more pronounced extent and dynamics of cell emigration were noted in da rats, while almost unchanged in ao rats sharp rise in pmn percentages h following trauma ( - % compared to rare pmns in control), followed by increase in lymphocyte numbers at later time points among lung cell emigrants was detected in ao rats. slower but persistent increase ( %, h following trauma and % and % on days and after trauma infliction, respectively) in pmn numbers among da lung cell emigrants was detected, which appeared to be activated, as judged by their nbt reduction capacity. increased percentages of peripheral blood pmns and increased state of leukocyte aggregation/adhesion were detected in both strains, but different levels of plasma tnf: increased levels in ao rats on days and following trauma, and initially but persistently high levels of plasma tnf alpha in da rats ( - fold higher compared to initial levels in ao rats). conclusions:different patterns of local (lung) and systemic changes in cell numbers and cytokine levels implicate differential posttraumatic migratory capacity of pmns vs. lymphocytes in lungs in ao and da rats. early diagnosis of acute intestinal ischemia by color doppler sonography e. danse, b.van beers, p.goffette, f.hammer,aav.dardenne, f.thys, p-f.laterre, m,s. reynaert, .lpringot dept of radiology (profb.maldague) and dept of intensive care ( prof m,s.reynaert), st.luc univ.hospital, brussels, belgium ob emergeny medical squad service is the most important segment in the process of saving the people, in the cases of mass accidents, like industrial accidents caused by the: explosion, fire, chemical poisoning, traffic accident, elemental catastrophes and the war. because of that, each emergency medical squad service needs to have in its motor-pool vehicle for the mass accidents/ for provoding at least people, wounded as well as the people became ill/. objectives: presentation of such special vehicle, produced by "zastava-kamioni" and it's medical-technical equipment. methods: descriptive and comparative analysis of the medical and technical characteristics, based on the actual norms/din, , iso , yus.../ results: on the base of doctrinaired requirements of the emergency medical squad in the case of mass accidents, our researches resulted in the following medical and technical characteristics -the vehicles for mass accidents are gvw/with a payload off cca - t, with the fixed, closed body, type: universal van, -technical equipment aggregates, stretches, anti-fire device, equipment for pitching the tent and for maintaing technical conditions of the work -medical equipment: linen bags with complete sets of bandage material, means for the reanimation and immobilization, for the infusion, medical instruments and remedies as well as the tent for lodging at least wounded and sik people. in federal republic yugoslavia, it was proposed such vehicles for the emergency medical squad needs. conclusion: we suggest to introduce this vehicle in the production range of the ambulance vehicles for saving, especially in the circles where can occur serious accidents. introduction : carbon monoxide (co) poisoning commonly generates central nervous system abnormalities though an important cardiac morbidity and mortality must be considered. long-term exposure to co with cohb levels < % may be more dangerous than short-term levels of - %. we report a case of an adolescent who after prolonged exposure to co developed a severe reversible cardiac dysfunction with low levels of bloed cohe c a.ase history : a year old boy was found comatose at home. his mother in the neighbouring bathroom died severn hours earlier of what was later proven to be a co intoxication. on arrival the gcs was / and the patient was breathing spontaneously. a postictal status with eventual postanoxic encephalopathy was suspected. a coh'b level of % was objectivated. the cardiorespiratory situation quickly deteriorated requiring mechanical ventilation. chest x-ray showed diffuse bilateral patchy infiltrates. ecg revealed signs of ischemia. severe left ventricular dysfunction was evidenced by pulmonary artery catheterisation and echecardiography and later by isotopic angiography (lvef %). treatment was intensified with inotropic support, intta-aortic balloon counterpulsation and oxygen therapy. the clinical course was further complicated by a crush syndrome and renal failure. the patient's condition gradually improved and he fully recovered without any residual lesions (lwf %) conclusion : even after prolonged exposure cohb levels can be misleadingly low. high tissue levels of accumulated co can be associated with coma and fulminant cardiorespiratory failure requiring advanced life support facilities. introduction : both neuroleptics (nlp) and tricyclic antidepressive agents (tca) can induce arrhythmias, prolongation of the qt segment and the pr interval and hypotension. we report a case illustrating that combined overdose of these agents increases the toxicity of each compound and the risk for adverse cardiac events. .c, gse history : a year old male ingested mg doxepin (sinequanr), a tca and mg prothipendyl (dominalr), a potent nlp in an attempted suicide. upon arrival in the emergency department the patient was unconscious (gcs / ), breathing superficially, and presenting signs of recent vomiting. physical examination revealed a taehycardia of b.p.m., an arterial blood pressure of / mmh g. ecg showed a brood qrs complex tachycardia. a chest x-ray revealed the presence of an aspiration pneumonia. laboratory investigation demonstrated increased levels of crcatine phosphokinase, lactate dehydrogenase and aspartate transaminase ; hyperglycemia and leucocytosis were present. the plasma concentrations of doxepin and prothipendyl were respectively gg/l (toxic level #g/l) and i.tg/l (no reference). treatment consisted of mechanical ventilation, gaslric lavage and administration of activated charcoal and iv fluids and antibiotics. a hemodynamically well tolerated veatricular tachycardia developed / h later. nahco ( meq/ h) was administrated inducing an ectopic atrial tachycardia with a normal qrs complex and prolonged qt. h after admission a normal sinus rhythm was present; the prolongation of the qt segment persisted for days. the patient fully recovered. conclusion : the treatment with nahco~, alkalizing the blood and thus increasing the protein binding of the tricyclic antidepressant molecule, can readily correct the potentially life-threatening cardiac arrhythmias and therefore should be part of the routine treatment of combined tca-nlp overdose. ob/ectives: the development of diabetes insipidus (di) in patients with brain injury is a known negative prognostic sign. the aim of this study was to investigate whether this is also a reliable early prognostic sign of brain death. methods: this is a retrospective study of patients treated" during a two year period ( - - to - - ) in our i.c.u who meeted the following criteria: ( ) coma score _< gcs within the first hours, ( ) positive brain ct scan on admission classified according to marshall's diagnostic classification (classes - ), ( ) normal renal function during the entire icu stay. for the definition of di were used the usual di criteria plus hypematriaemia (serum na" >_ meq/l). survival was defined up to the th postadmission day. conclusions: according to the findings of this study, the development of diabetes insipidus in brain injured patients seems to be a highly specific index for brain death (positive predictive value = . ). however, further prospective studies are needed for the definitive evaluation of these findings in such patients. emergency care in italy, despite all efforts, is still lacking a nationwide organized prehospital care system and, until today, there are only different regional solutions. the majority of these realities imply rather simple ambulance first-aid services without attending emergency physicians and without resuscitation equipment. the emergency medical service (ems) system in falconara m., italy, was implemented in august by a collaboration between the school of anesthesiology and intensive care of the university of ancona and the, already existing, volunteer rescuer organisation "yellow cross". according to the guidelines pubblished in [ ] the pre-existing equipment of the volunteers was completed with type a ambulances and special equiped motorcar (patient monitor, defibrillator) for ambulance indipendent physician transpur[. a special data collecting schedule was created to memorise every emergency intervention in a computerised data-base. the intraining members of the school of anesthesiology and intensive care provide hour ready intervention. in this report the authors describe their experience concerning primary firstaid medical interventions. for a preliminary evaluation we considered, retrospectively, consecutive emergency interventions in the time period from novembre , to april , . the emergency physicians treated male ( %) and female ( %) patients, patients died before hospital admission and patients ( %) were treated at home by the ambulance indipendent physician and did not need any further medical treatment. in the same time period year earlier (november to april ) without attending physician the volunteer rescuers transferred all first-aid interventions to near-by hospitals. we conclude that the presence of an attending, iudipendently motorised physician in emergency interventions is essential for the establishment of precise priorities and may be helpful to reduce hospital admissions by ambulance intervention, though reducing primary" health care costs. we have developed the method of liquor filtration which allows to purify the cerebrospinal liquor from blood and its decay products in the subarachnoid bloodstroke. the hemipermeable dialysis membrane was used as a filter, which lets only in water, electrolytes and substances with small molecular weight. the liquor filtration was used for the treatment of patients with the subarachnoid bloodstrokes of different etiology. the perfusion of liquor was performed at the rate ml/min in the recirculatory mode. its duration was - min depending on the bloodstroke intensity. the filtration makes possible the most completely purifying of the hemorragic liquor, the reducing of the content of blood ceils and its decay products - times as less. the monitoring of the patient's state during the perfusion didn't revealed the departure from the norm of the main vital part. the liquor filtration technique compares favo-~ rsbly with the routine method of cleaning by the absence of toxical effect of heterogenous solutions on the central nervous system. the filtrstion of the cerebrospinal liquor in the subarachnoid bloodstroke sllows to provide the the early cleaning of liqour, the regression of meningeal syndrome and to improve the patient's state of health. e tabli~mczr bd ~ of rei~idnal medical first-aid zhoulittoing, ed., tan zi, m.d. dept. of sargery, the first teaching t[ospitat, yejin-l)a-l)ao, wuhan fltlna objectives: the medical first-aid is the most important task of the public hc atth department. in general, single hospital model couldn't fatty, effective ly rescue mony severe patients who need mergant treatment in the scene. bub establishing the medical first-aid network, the severe patients can be given the most timely und the most scientific emergent treatment. so that, the suc cessfut rate of the saving wilt be greatly increased. methods..; our hospital is a general big hospital. through developing and cons tructlng for more than ten years, the medical first-aid network distributed art over the area under our jurisdiction has been set up. it consists of thr ee units: the medical first-aid unib center comartd and mnagment unit, co m~nlcation and tiaison unit. the principle of the network operation is with oat having to far to mergoncy, specialized emergency and the best merge acy. results: the results of the network operation were notable. cmpari~ the to tat successful rate of the saving ( . ~), the successful rate of saving tra ma ( .~), the suscessfut rate of saving shock ( .~) and the successful rate of cardioputmonary resuscitation ( . ~) daring the three years after t he network operated with these before ( . ~), ( ]. ~), ( . ~) and ( ft. ~), the successful rates after operating were remrk~iy higher ( p<i).o ). conctusions~ the above results showed estabiishmnt and mena emont of region at medical first-aid network had very si~nificont action during mergentty s avin the severe patients. moreover, the regi~at medical first-aid network atso take an important part in prevention and health protection of the mass. objectives: se related mortality is due to the occurrence of both rv and lv dysfunction evoking cardiogenic shock and pulmonary edema (f. abroug, intensive care med ; s. nouira. chest ) . prospective evaluation of scorpion antivenon (sav), the only available specific treatment, is lacking. the aim of this study is to assess the effects of sav on the basis of a case-control study. methods:among consecutive victims of se presenting to the emergency department, were managed using sav (group sav+). these patients were matched to envenomated patients who did not receive sav (group sav- chest injuries are the cause of death in % of trauma fatalities and a major contributing factor in an additional %. pneumothorax is a major complication of chest injuries and can be initially overlooked bringing to additional morbidity and mortality especially in patients who require mechanical ventilation. the real incidence of pneumothorax in severe blunt chest trauma hasn't yet been established, as many pneumothorax can be missed on the initial chest x-ray (cxr) and computed tomography (ct) has not been routinely used. to evaluate the incidence of pneumothorax in patients with severe blunt chest trauma. methods: a prospective study. from january to december , all trauma patients with one of the followings conditions: fractures of four or more ribs, signs of lung contusion on the initial cxr or presenting a severe hypoxemia on admission (pao /fio < ) in the absence of pre-existing pathologies, were evaluated by initial cxr and subsequently submitted routinely to a ct. results: severe trauma patients were considered. of them, presenting a severe hypoxemia on admission, had no evidence of major chest trauma (ais< ). hypoxemia was the consequence of severe trauma in other districts; these patients were therefore excluded. patients with severe thoracic trauma (ais>= ) were admitted into the study. the mean iss was . ( - ). thirty-six patients required artificial ventilation for at least hours during the icu slay. three of them, who had a tension pneumothorax, were submitted to an emergency thoracic decompression on the field by the emergency helicopter team. in cases pneumothorax was diagnosed an the initial cxr more patients had a pnx which was identified only on the ct. in cases a large pnx with lung collapse was missed on the cxr. in our group of severe blunt trauma patients, % ( / ) presented a pnx that required the insertion of a thoracic drainage. only one third ( / ) of the pneumothorax could be recognised on the initial cxr, while other were decompressed before performing the cxr. as many as % of the cases of clinically significant pnx were missed on the cxr, and a ct performed soon after admission allowed an early diagnosis bringing to changes in the treatment. (as the patients were mechanically ventilated a chest tube was inserted in all these cases). in cases, the initial cxr overlooked a huge tended pnx which was the cause of hemodynamie instability. conclusion: in patients with severe blunt chest trauma even large pnx can be missed on the initial cxr. moreover due to the non compliant compressible lung, a % pneumothorax which can be recegnised only on a ct, can bring to high intrapleural pressure altering eardiopulmonary function. n. andoeli , .~osid, m.zesevid, m.risovid, d.stepi , d.djokid b~rga~yc~qterclinicalcaqterafserbia, belgrade cb~ctives:~lis study ~ the use of ~rq]ofol earbired with k~t~ine (aq a~sjgh~ic s@~qt widn inirjrsic armlgesic pro~mities) or with fsqtmtyl,with psrtial azgmsis an hgenxlyn-a~ic ~ durirg ~ ~ re:~ver~ f~m ~ in hxh ~ of ~ti~. ~: yali~mial and ~bod: a~it p~tie~ts a~ i-ii were included in ibis shxly. patients were rsrd]nly dieided in two ~ns. all d~tie~ts ~me given - prcpofol bolus doses (o, ~gkg) for ird~iqn of ~. ~ia ~s m~sjn~ with an infusion ~ ~ropafol. as sdflitianal were given fan-i~l (o, n]g) ~tely before ~ anj trad~e~ irfojoation followad by feasted bolus of o,i mg in ~ro o l.patients in gr~ o received i~ (an initial bolus dose of rg slowly intcavax~ rd mg as infusion over ~ rain) .infusions of pro~fol or imcpofol with kg~mine ~ stopfsj - rain ]:~o~ extuhation.arterial blood ~ (sistolic arterial blood preassu-re~zap,mean ~rterial blood pr~,d~lic arterial preassure-[zp a~ h~art rate-~) ~ m~ before induction of a~ io, snd rain aftem ~ intutation. results: arterial blood preasstre ~s decreases duri~ irn~ction of sn~wd~sia in hy~ ~n~s,tnt mare in th~ ~ who r~eived fsqtanyl.~ere w~s statisticslly sifnific~ntly difemerme dmir~ m~ of an~ia. arterial blood r~easatre and heart rate were stable in the t-..e~min -~a ~. all th~,fl-e keta'nire grcqo hsd e~rly :~e~y time. ctrmlusi~s: ~e ombiretion of protxfol wilh keta/ne for irduorion a~d ~ of sn~sd~esis w~s yell accept~ by p~tierfcs anj coald he ~ as an alterrstive ~o ccnva~icrsl a~es -d~sia. objectives : assess the relation between cytokine or endotoxin release and indices of splanchnic malperfasion after hemorragic shock in multiple trauma patients. ]~r study was approved by the local ethical committee. trauma patients admitted to the emergency room who met the entrance criteria of more than hour map < mmhg or use of vasoactive agents or blood lactates > mmol/ were selected for study. a nasogastric tonometer (tonometrics, inc, plastimed, france) and a swan ganz catheter were placed on admission. phi, lactates, hemodynamics, plasma cytokine and endotoxin concentrations were measured on admission and at . , , , hrs. an immunoradiometric assay was used to determine plasma concentrations of il (n< . ng/ml) and tnfc~ (n< pg/ml). plasma endotoxin concentrations were measured using a chromogenic limulus assay (n< . eu/ml)( endotoxine unit= pg). results : severe multiple trauma patients (age = _+ yrs, iss = -!-_ , saps = +'~, mean-+sd) were studied. they received + packed red cells during the first h. mean duration of collapsus before inclusion was . _+ . hrs. death occm'red in ~tients. ~ pglml, *: ng/ml, etox : endotoxin(eu/ml), lact: lactate (retool/l) a significant correlation between initial il level and saps was observed. in the early post-injury period phi, sao , svo , vo were significantly associated with ;il release (p< . at ho, h , h ). later a significant correlation existed between lactates and ii (h , h ). a peak of tnf was detected at and hrs. it was associated with low phi and low arterial ph of the early post-injury period (p< . iat ho, h , h ,h , h ) and with high lactate levels of later period (_>h ). only the late release of endotoxins (i{ ) was correlated significantly with initial !oxygea-delivered parameters. iconclusion : there was a marked increase in il in the early phase of trauma . i and tnf release after major trauma iwith hemorragic shock is associated with splanchnic malperfusion, as assess by the ivery low values of phi. lactates seem to be a later indice. toxic effects are a well-known complication of an overdosage of prescription theophylline. what is less known is that over-the-counter (otc) asthma medications contain theophylline, and that in some cases this might cause toxic effects. a case seen by us involved toxic effects from theophylline in an otc medication and to date is the only published case in the english literaturet the rationale for this study was to delineate the otc products containing theophylline from whatever data sources available. hyperthermia frequently occurs in intensive care treated patients and intentional application of whole body hyperthermia together with chemotherapy is a therapeutical access to treatment of malignant disorders. anaesthetic support is required in either condition. due to the marked decrease in systemic vascular resistance seen in hyperthermia an additional vasodilatory effect of the anaesthetic is unwanted. the vascular effects of anaesthetics in hypertherm organisms is not known in detail. therefore, we performed an experimental study to detect the effects of inhalational anaesthetics in whole body hyperthermia. in sprague-dawley-rats katheters were inserted into trachea, jugular vein, and carotid artery. for continuous monitoring of cardiac output a flow probe was placed around the aortic arch. the rats were mechanically ventilated with different concentrations of inhalational agents in oxygen. we compared the effects of enflurane, isoflurane, and halothane in stepwise increased body temperature by submerging in a temperature controlled water bath. results: isoflurane lowers arterial pressure more than halothane or enflurane. the inhalational anaesthetics lower the cardiac output similarily and independently of temperature. isoflurane decreases systemic vascular resistance independently of core temperature and the decreasing effect of halothane on the resistance is completely abolished in hyperthermia. conclusions: the influence of hyperthermia on the systemic vascular resistance is dangerous. this allows no additional effect of the anaesthetic management. in spite of the vasodilating effect of inhalational agents in normotherm subjects, this effect is abolished in hypertherms using halothane. the condition of management of analgosedation in hyperthermia is different from normothermia. objectives: to evaluate a bedside computer processed cerebral function monitor for assessment of brain wave activity when clinical/visual clues are not present. methods: ten icu patients undergoing neuromuscular blockade monitored with the aspect brain wave monitor from january to june , . results: time to onset and depth of sedation were readily apparent to icu physicians not specifically trained in eeg reading. objectives: to determine whether non-depolarising neuromuscular blockade reduces oxygen consumption (vo ) in sedated, apnoeic patients. methods: haemedynamic. metabolic and oxygen transport variables were determined in sedated, apnoeic patients with severe acute lung injury. all patients were ventilated using a puritan-bennett ae ventilator with integrated metabolic monitor. inclusion criteria were; ) stable cardiorespirator s" status; ) systemic and pulmonary artery catheters already in situ; ) inspired oxygen < %. patients were sedated with midazolam or propofol to abolish response to verbal stimuli, and sufficient morphine or alfentanil to abolish all spontaneous respiratory efforts. following baseline measurements, neuromuscular blockade was induced with intravenous vecuronium, ug/kg, followed by an infusion of ug/kg/h to maintain the train-of-four ratio at . a further four sets of measured and calculated variables were obtained at min intervals. results: statistical analysis was by repeated measures anova. there were no significant changes in any variable over time. the changes in calculated oxygen consumption (vo fick) , and measured oxygen consumption (vo gas), and in energy expenditure (ee), are shown in the table. objetive: to study the effects on coronary hemodyrtamics and myocardiai metabolism of administering propofol during postoperation sedation of patients with normal coronary circulation and good ventricular function undergoing cardiac surgery. patients and methods: patients ( women and men) undergoing aortic and/or mi~-a/ valvular cardiac surgery were selected, with an ejection fraction greater than . and normal coronary circulation. for postoperation sedation propofol was administered in . mg/kg i.v. bolus, followed by a . mg/kgth perfusion. all data were registered before administering propofol and after minutes, the patients being hemodynamically stable and a rectal temperature of _+ . -~ systemic and pulmonary hemodynamics, and global, as well as regional myocardial blood flow, and metabofic variables were measured. results: the patients studied were about years old, and the average period of aortic cross-clamp was . min. the adminstering of propofol caused a decrease in the coronary blood flow (- %), great curonary vein flow (- %), myocardial oxygen consumption (- %), regional myocardial oxygen constanption (- %), myocardial oxygen extraction (- %), regional myocardial ooxygen extraction (- %), while coronary vascular resistances and global coronary vascular resistances did not change. oxygen saturation increased in the coronary sinus (+ %) as well as in the great cardiac vein (+ %). in no patient were significant changes suggestive of myocardial ischemia objectified. there was also found a decrease in systolic (- %), diastolic (- %) and mean (- %) arterial pressure, systemic vascular resistance (- %), and cardiac output (- %). conclusions: in accordance with the clinical conditions of this study, the administering of propofol is not likely to cause changes in coronary autoregulation, oxygenation and myocardial metabolism. obietive: analyse the effects of . % "end tidal" isoflurane (sedative dosage) on the metabolism and coronary hemodynamics during the postoperation period of patients undergoing cardiac surgery. patients and methods: patients ( women and men) undergoing aortic and/or mitral valvular cardiac surgery, with an ejection fraction greater than . and normal coronary anatomy, were selected. after the surgical operation, . "end tidal" isoflurane was administered for postoperadon sedation. the determination of variables to be studied was carried out before and minutes after administering isoflurane, die patients being hemodynamically stable and a rectal temperature of _+ . -+c. systemic and pulmonary hemodynamics, and global, as well as regional myocardial blood flow, and metabolic variables were measured. results: the average age of the patients studied was -+ . years. during surgical operation the period of aortic cross-clamp was . _+ . rain. the administering of isoflurane was followed by a statistically significant drop in coronary perfusion pressure (- %), coronary vascular resistance (- %), regional coronary vascular resistance (- %), regional myocardial oxygen consumption (- %), regional myocardial oxygen extraction (- %) and accompanied by a significant rise in oxygen saturation in the coronary sinus (+ %) and in the great cardiac vein (+ %). myocardial oxygen consumption, myocardial exu'action of lactate and regional myocardial lactate extraction did not change. in no patient were enzyme or electrocardiograph changes objectified. systolic (- %), diastolic (- %), mean (- % ) arterial pressure, and systemic vascular resistances (- %) decreased, while cardiac output did not. discussion: the administering of . % "end ddal" isoflurane, in the clinical conditions of this study, produced a decrease in systemic arterial pressure due to a reduction of systemic vascular resistance without deteriorate cardiac output. at coronary circulation level, has and effect on coronary autoregulation but had no effect on oxygenation and myocardial metabolism. the idea of tiva implies the realisation of major anesthesia components (los of consciousness, neurovegetative inhibition, analgesia, myorelaxatiou, providing the adequate gas-exchange) through i.v. introduction of drugs exclasively. aim: providing for the main tiva components with minimal side effects of the drugs used, taking into consideration the patients characteristics and the surgery specific character. methods: anaesthesias have been conducted in patients aged years ( females, males), undergoing planned and urgent operations with the pathology of lower, extremities, perinaeum, small pelvis, hypogastrium and with reserved spontaneus respiration against a background of % insnffladon through mask. operations lasted from . - . h. anaesthesia adequacy was assested by constant monitoring: "cardiocap" (nibr hr, rr, sao , t), through glykhaemia level and mimicry reactions. standart premedicatioo of m-cholinolytics ( . mg/kg) and h -blockers ( . mg/kg) on the operational table was sumplemented by administration of . - . mg/kg of lidocaine, . . mkg/kg of clonidine, . - . mg/kg of pentamidine by the tachifilaxia method. the premedication adequacy was assessed through haemodynamics characteristics. sedation: . - . mg/kg of droperidoi, .l- . mglkg of diazepam and analgesia: - mkg/kg of phentanyl, . -- . mg/kg of ketamine were introduced fractionally according to indications. infusion rate of ringer-lactat solution was - ml/kg/h and depended on the intraoperational blood loss volume and on the patients preoperational condition. the duration of postoperative analgesia was registered. results: clinical assessment of analgesia according to this techniques allowed to decrease the anaigetics dosage to the subauaesthetic levels. smooth stabilisation of haemodynamics (bp) at proper age norms in patients with the initial hypertension by the -th min. of anaesthesia as well as the absence of its increase in response to the additional introduction of anaesthetic have been achieved. (hr) had no abrupt changes and remained in the range of - per rain. adequate external breathing: decrease (rr) by - per rain., with sao increase from % to - %. hypoventilation was avoided by respirate ventilator. according to unauthentic data the glykhaemia level had been lowered by -t % to the end of the operation with the initial moderate hyperglykhaemia of up to mmol/l the cutaneous covering grew warm and got pink colouring. no mimicry reactions. in the postoperative period patients were in the superficial sleep state ( - ) and analgesia lasted - b. there were no complications due to anaesthesia. conclusion: combined using of bz, opiates, neuroleptics potentiate the i.v. anaesthetics effects allowing lowering of each tiva component dosage and, as a consequence avoiding their negative influence on respiratory and heart vascular systems. complex application of adrenergetics (therapeutic doses of cionidine and pentamini with using of taehfilaxy effects) permitted to provide for analgetic and neurovegetative components of general anaesthesia under subanacsthetic doses of tiva main components, and manifestation of hyperdynamic reactions of haemodynamics decreased while using of lidocaine -the economicai activity of heart-vascular system. good level of muscle relaxation was achieved allowing for widening of surgical intervention extent without respirator ventilators and inhalation anaesthetics application. anaesthesia is easily controlled due to fractional introduction of drugs with quick recovery of cns functions after anaesthesia. postanaesthetic analgesia is increased while concurrent opiates doses are decreased. absence of marced haemodynamic, endocrine and metabolic reactions during the operation and after it resulted in shortening the period of patients staying in hospital. a yo white man was admitted to hospital for dyspnea and a productive cough. he had cabg in past, but no recent cardiac ischemia. physical exam: decreased breath sounds over right lung. chest xray: consolidation of right lung. admission medications included diltiazem, furosemide (both were continued) and trazodone (which was discontinued). admission ecg: sinus rhythm, qt . /qtc . sec, with st and t wave abnormalities similar to prior tracings. he required intubation and mechanical ventilation for progressive hypoventilation and hypoxemia. between icu days and he received haloperidol, - mg/d (cumulative dose rag) for agitation and delirium. icu day : qt . /qtc . sec. icu day : for better control of delirium, trazodone " mg q hs was added. icu day : he developed frequent nonsustained ventdcular ectopy. icu day : qt . /qtc . sec, pha . , paco mm hg, pao mm hg, k . meq/l, mg . meq/l. later in icu day the patient had brief episodes of torsades de pointes, each responding to precordial thump, and finally rhythm stabilized with i.v. lidocaine and magnesium. haloperidor and trazodone were discontinued. ecg was unchanged and myocardial infarction was ruled out. next day, icu day : qt . /qtc . sec. torsades de pointes, a form of ventricular tachycardia characterized by a twisting qrs axis, is commonly associated with qt prolongation. haloperidol is used frequently in icu for control of agitation and delirium, with reported doses up to mg/day. over past decade, cases of torsades de pointes with prolonged qt related to haloperidol have been reported. trazodone may also prolong qt and cause ventricular arrhythmias, especially in patients with pre-existing cardiac disease. in this patient, trazodone likely exacerbated qt prolongation from halopeddol leading to torsades de pointes. critical care physicians must be aware of this interaction. it is imperative to follow the qt interval for patients receiving halopeddol, especially when another drug also known to prolong qt is added. one must consider discontinuing the drug when qt/qtc becomes prolonged. objectives: analgesics and intravenous anesthetic drugs are routinely used in critically fll patients, who often suffer from a secondary impairment of the immune system. previous in vitro studies have demonstrated inhibitory effects of these drugs on polymorpho nuclear cells (pmn). the potentially important role of endothelial cells (ec), however, was not investigated, since suitable test systems were not available until recently. therefore a physiologically more relevant in vitro migration assay through cultured human endothelial cell monolayers (ecm) we established. using this assay system, the comparative effects of fenlanyl, sufentanil, propofol and the known pmn inhibitor thiopontal were tested. methods: human umbilical vein endothelial cells (huvec) were isolated and cultured on microporous membranes (cyclopererm) until an ecm was grown. pmn from male and female volunteers were separated by standard procedures. ecm and pmn were preincubated with clinically relevant concentratious of thiopental ( m), propofol ( p_g/ml), the solvent of propoful (intralipid), fentanyl ( ng/ml) and sufentanil (sng/ml). after preincubatiun (ecm minutes, pmn minutes) with the reslx~tive drug, leukocyte migration towards the chemoatfractant fmlp ( o - m) was measured in a two chamber well system for hours. the migration rate of untreated (untr.) and treated (treat.) pmn through untreated and treated ecm were determined. as a control untreated pmn and untreated ecm were used. results are given as means from independent duplicate determinations and expressed as a percentage of control (table) . statistical analysis was done with student's t-test. results: clinical concentrations of fentanyl, sufentanil and prupofol showed similar inhibitor~ effects as the known pivin inhibitor thit e ). % conclusions: for the first time we could show that analgesics and anesthetics exert their inhibitory effects not only on pmn, but mainly on the interaction of pmn with endothelial cells. moreover, we could shmv a significant suppressive effect of the opinids fentanyl and sufentanil on both ec and pmn. the known inhibitory effect of thiopental obtained in ec-free test systems were also confirmed in our physiologically more relevant assay system. objectives: to investigate when and how sedation is used in a consecutive cohort of patients admitted in a large sample of italian intensive care units (icus), gathered in a network named giviti, representative of the italian icus system. methods; the study called for a recruitment period of one month, from january to february , , data collection included age and other demographic variables, acute diagnostic broad profiles, severity of illness scores, treatments, lenght of stay and vital status at icu discharge. as concerned sedation, each patient was observed until discharge or for a maximum period of seven days. information on all the drugs used for analgesia/sedation, the route and modalities of administration, the timing, dosages and purpose of the administration have been recorded. results: the study involved the cooperation of icus, of which enrolled at least one case. the total sample included patients. overall, . % of patients analyzed (t / ) received at least one prescription of sedative during their stay. globally, at least one sedative drug was prescribed to these patients in days in icu. although over drugs were reported to be used, pharmacological principles accounted alone for % of all prescriptions. opioids were actually used in % of prescriptions; propofol in % and benzodiazepine in . %. as regards the way of administration, intravenous administration was applied in % of cases and, followed by intramuscular in . %. moreover, non-steroidal anti-inflammatory drugs (nsald) were used in % of patients and neuromuscular blockade agents (nmba) in %. detailed analysis on certain subgroups (surgical, trauma, ventilated patients etc.) have been also carried out in order to describe the practice of sedation in these peculiar subgroups. findings will be widely discussed during the presentation. conclusions: these results should be interpreted keeping in mind how peculiar is the intensive care setting compared to many other less complex settings of hospital care. in conclusion we thought it was important to present the data currently available in the most neutral form, to start moving in a direction which will enable us -by means of more specific and detailed studies, and with the cooperation and involvement of all those participating in the project -to shed light on one of the many aspects of medical practice in the field of intensive care which deserve closer attention. introduction: the aged run perilously high risks in cardiac surgery: among others, of haemodynamic fluctuations, respiratory depresskm and organ failure. response to anaesthetics is a crucial determinant for post<)perative complications, none the less being reintubation due to mechanical ventilation difficulties which increase morbidity, mortality and intensive cdre unit (icu) stay. objective: we wanted to assess our a,aesthesia window (selection, and a view of the induction -extubation period) for predicting safe and swift awaking, thus: icu dismissal for the aged. methods: in , selected patients (pts) (> y, f) followed a regular elective cardiac surgery protocol (propofol given at precisely designated time intervals). upon cu arrival, they were subjected to an admission protocol. our predictive criteria for early extubation at h included: a) alertness and ready response to commands; b) adequate gag reflex and sufficient protection for respirak)ry tract; c) pao > mmhg with flu < . ; d) stable ph> . with spontaneous respiration; d) stable haemodynamics without dysrhythmias; e) adequate perfusion and diuresis (> .(i ml/kg/h); f) mediastinal bfeeding< ml/h for at least h; g) normothermia (core temp> ~ and no shivering). subsequent reintubation was for: ) rr> /min; ) spontancx)us ventilation for rain with paco > mmhg; ) pao < mmhg with fio > . ; ) ph> . ; ) heart rate>] bm; and/or ) non mental alertness; and ) other medical disorders, after which adequate weaning therapy was necessary. then, successful weaning after h was considered: ) spontaneous breathing without any forrn of mechanical assistance; ) stability in haemodynamics; and ) elimination of fever threat. results: pts ( %) were extubated at h without complication; other pts ( %) at h but had to be reintubated because they were hypoxic and began weaning therapy; finally, they were all re-extubated by h. only pts ( %) proved problematic. conclusion: a,aesthesia wimhlw options (selectkm, extubation, reintubation and weaning) predicted quick (times propofol administration) and safe (rigid criteria) extubation ( %= h and %= h), exempting pts with developed post-operative complications ( %=extubation< h) unrelated to al~aesthesia window or icu protocol. dismissal and recovery then became an abbreviated question of time. fifisetll p, domeneg~i ~, sforzini i., veronesi i~, maconi a.g. *, breg~ massone p.p h [] ic+pca request conclusions:using e~aprenorphine, a synthetic,long-acting, ago-antagemist opinid drug as analgesic, in the major surgery we obtained the best clinic results with association of conttheus infusion of haft dose drug with bohts of pca in the first - hours and just pca in the secmad day after surgery when the patient is less sleepy. in this way we dent have a great sav~g of suppled drug but the major well-belng of patient without ~erious side-effects and quick mobilization; the dosage used don't compromise a good awake of patient: all patients are sleepy but ready for answer, no allueinatian, bradipnea but not less than b/m without ipoxia. also the patient proffered this kind of truit meut than the traditional at demand. the ward staff feel it useful] and rehabl~ the negative feed-back technology of the electronic infuser system makes possible to use it safe in the ward with high drug's concentration too. the infusion rate of low dose of drug assure a continuative analgesic covering ~n the first postoperative periad; the pca mode involves the patient him-self in the managemenl of therapy and enables him to choose the best way to confront the dll~icuity of postoperative period without call medical stall using pca-device we have had no probicm~ no accident. analgesia during extracorporeal shook wave lithot ripsy a .levit, b.grinbezg regional hospital, ekaterinbu~g, russia b~ectives: our task was to compare ~he analgetic effect of norphin and tramel. methods: study was made of two groups of uro-li~patients aged - . group a ( patients) received baprenorphine hydrochloride (norphin) at dosages of #. • mg/kg. group b ( patients) received tramadel hydrochloride (t~aasl) st dosages of . z . mg/kg. before the procedure diazepam was administrated i.v. ( . ! . mg/kg). blood saturation (spoz), hemodynamics incides (bp, hr,sv,co,sap,svr) were examined and the patients' subjective assessments of snsesthesis quality were analyzed. the hospital ethics committee approved the investigation. results: when using norphin hr increased by . % on the onset of the procedure while sap and sv decreased by .%% and . %, respectively (p< . ). however, there were no reliable co chsnges. spoz ~educed by @. % (p< . ) and remained lower than the initial one after the procedure was oyez. when administrating tramsl min. after ste~ting the procedure sap and svr increased by ~ . % and . % respectively. sv and co decreased insignificantly. nine patients in group b saffeting some dlscomfo~t needed additional tm~msl in~ection. in the course of the whole p~oced~e spo, was constant and was highez than that in ~he case of nozphin (p<o. ). conclusion: respiratory suppression by no~phin can limit its use in case of lithotzip@y while the advantages of tremsl a~e: lack of dyspnoe and good contact with the patti-b_ the role of uncommon agents of antinociception, placed epidurally, in the control of pain transmission in the spinal cord is well documented. somatostatin as an inhibitory agent is found in the dorsal horn of the gray matter of spinal cord. the effects of somatostatin is similar to the opiates if injected into the epidural space (ref. i, , , ) . the aim of the present study is to present the clinical effect of above mentioned palliative therapy in the case of cancer and non cancer pain. informed consent had been obtained from every patient before treatment was initiated under the legalisation of the local ethics committee. using the permanent epidural catheter and continuous infusion pump, we administer somatostatin in the dose of up to microgram per hour for one up to three days. the patients paln feeling was evaluated using a vas (visual analogue scale). we found that the opiate resistant pain level decreased by %. the rest pain could be controlled by pereral opiate analgetics or by combination of somatostatin and an opiate plus a local anaesthetic agent epidurally. theoretically, it seems that epidural administration of somatostatin and local anaesthetic agent is useful in the control of acute pancreatic pain and systemic effect of somatostatin is beneficial in the treatment of acute pancreatitis. few studies have been performed in the critically ill (ci) and because of the complex pharmacodynamic and pharmacokinetic changes that occur, it is difficult to predict accurately drug responses and interactions in individual patients. midazolam (m) is a watersoluble benzodiazepine with a rapid onset and short duration of action in normal individuals; however its metabolism is decreased in the ci. critical care physicians every day experience suggest that among the ci there is a different pattern of response to m; here it is hypothized that such a response could be due to different metabolic behaviours of ci. m (i.v.infusion rate - rag/h) and antipyrine ( rag p.o.) were infused to ci with ( patients -group ) and without ( patientsgroup ) endotracheal intubation. blood samples were collected at fixed times during and after m infusion. total urine nitrogen and antipyrine elimination half-life demonstrated different metabolic characteristics in group chypermetabolizer") as compared to group chypometabolizer"). results follow. the results of our study are preliminary and more kinetic data in critically ill patients are needed to statistically confirm our approach of "hypometabolizer" and "hypermetabolizer". objectives: some clinieai and experimental studies suggest that propofol decreases myocardial contractility in coronary artery bypass grafting (cabg) patients. the intrinsic negative inotropic action of the drug may be independent from changes of preload and afterload, whereas the myocardial depression induced by propofol may depend on changes in ca ++ ious availability. aim of this study was to verify the hemodynamic effects of propofoi in a group of cabg patients with uneompromised contractile function and to minimize myocardial depression, during induction of anesthesia, choosing to associate calcium chloride (cac ) in an other group and to define its role in producing this effect. methods: fourty patients, randomly divided in two groups ( pts a and pts b), undergone elective cabg, were enrolled in this study. anesthesia was induced by senior anesthetist in both groups by means of fentanyl mg• kg < in ", pancuronium . mg x kg - and propofol mg • kg - in ". a blind investigator administered via another venous way at same speed ( ") saline in patients of group a and mg x kg - cac in patients of group b. hemodynamic data (heart rate hr, mean arterial pressure map, mean pulmonary artery pressure pap, pulmonary capillary wedge pressure pcwp, central venous pressure cvp, cardiac index ci, stroke volume index svi, systemic and pulmonary vascular resistances indexed svri and pvri) were obtained at baseline (to), ' after anesthesia induction (t ) and " after tracheal intubation (t ). results: hr decreased moderately in both groups (p = ns). map decreased as well, more markeatly in group a at ti and t . this trend was statistical significant (p < . ) in both groups. pap, pcwp and cvp unchanged following induction in any of two groups. ci decreased in group a (p < . ) dramatically dropping at t , while in group b it showed a negligible decrease at t (p = ns) and value similar to baseline at t . svri and pvri did not exhibit statistically significant changes. conclusions: the use of propofol as a starter of anesthesia in cabg patients allows to reduce total dose of fentanyi, dramatically reducing post-operative intubation time. propofol-fentanyl association prevented the hyperdynamic response to stress (i. e. laryngoscopy, intubation) but severely depressed ci and svi. cac simoultaneous administration effectively minimized the negative inotropic effect of propofol. moreover no unwanted side-effects due to cac were observed. diseoordinated labor activity (dla) is one of most serious in obstetric pathology.medication sleep effect to a woman in birth is of limitation of pathologic impulsation from the central nervous system, but it does not influence processes resulting in and supporting dla on the organ level. constant discoordinated uterine contractions during medication sleep (ms) imerease disturbances of uterine blood flow, organ hepoxemia connected with hyperergia of vascular wall and myometrium to catecholamines, that reduces efficiency of anesthesiologic protection. we applied hexoprenalin in complex with ms to primaparas. efficiency control was being accomlished through hysterograms, grade scale of analgetic effect where hemodynamics reaction to pain, significance of emotional reactions and their vegetative manifestations before and during ms were registered, and also through hydrocortisone level in plasma before and during ms. the examined women's average duration of ms was hours more than in control and made hours, though their average labor duration and in control was the same and made hours. % of the examined women experienced independant labor, as for the control group -only %. supplementary methods of anesthesia were required in % in control,that increased medicamentous depression of the fetus, but for the examined group -only in %. the examinees's newborns experienced favourable terminations, in control newborns were in state of light rate asphixia. analgetic effect was complete in control just in i %, and of examinees -in %. on the women's hysterogrnms before ms discoordinated contractions were registered on the background of increased tonus. during ms in control similar uterine contractions were constantly registered, but for the examinees they were not marked at all or had the proper character. the examinees' hydrocortisone level was reduced for % and in control only for %. the study has allowed to make a conclusion that hexoprenalin applications in complex with ms in case of dla make anesthesiologic care safer and more effective, promote simultaneous removal of patholgic processes in the central nervous system and uterus, which lead to dla development. objectives: the aim of report is to present a clinical study results for the evaluation of anesthesia for a patients in unconscious states by eeg examination: methods: the study was conducted on patients after a severe abdominal operations on stomach and intestine and on one patient after traumaticat exarticulation of upper extremity. all patients have different unconscious state levels from somnolence to coma ]. also thay hav~ had respiratory insufficiency and control mandatory ventilation have been used. we were used intrave,~ous injections of morphine hydrochloride from initial dose of mg. than we were increased the dose to mg i.v. by drops with an accompanying eeg monitoring and fourier spectral analysis. initially all patients have had -rhythm with slow and a-activity. an c~-activity index have been lower than %. results: after anesthesia the o-and a-activity have disappeared. the or-activity index have increased to %. also we have noted decreasing of the unconscious state levels to a possibility of a verbal contacts ( - points gcs). conclusion: the quality of anesthesia could be evaluated by eeg monitoring. a regaining consciousness afte~ the injections of high doses of morphine, probably, may be a result of an opiate deficiency (full or partial). anesthesia with the following drugs: clonidine, l-arginine, l-n-arginine-methyl-ester (l-name), and their combinations. tail-flick latency (tfl) was determined at time zero and min after each treatment. clonidine (i- ~g/mouse) prolonged tfl in a dose-dependent manner. at a clonidine concentration of gg/mouse, tfl increased . -fold compared to time zero. l-arginine increased tfl at a high concentration (i gg/mouse). l-name suppressed tfl . -fold compared to time zero at a concentration of gg/mouse. conclusion: we have found that no is involved in clonidine spinal analgesia. studies are currently being undertaken to assess the effect of combination treatment of the above drugs on clonidine supraspinal analgesia. objectives: hemodynamic changes ussualy accompany laryngoscopy and tracheal intubation.the aim of this prospective study vas tu present the effectivness sufentanil in preventing reflex circulatory respone of laryngoscopy and tracheal intubation and provides stable hemodynamio condition for induction of balanced anaesthesia. methods: adult asa i-ii patients sheduled for elective surgery.they were allocated randomly and divided into two groups:fifteen patients received single bolus of placebo prior to laryngoscopy.and tracheal intubation. anaesthesia induction was then performed with thiopental (smg/kg) and atracurium ( , mg/kg), followed by neurolept anaesthesia. mean arterial preassure (map) and heart rate (hr) were measured before, during and min after intubation. althought ecg was recorded at the same time intervals. results: the groups were compared with regard to the changes in arterial blood pressure,heart rate and electrocardiogram. mean arterial preassure and heart rate were incresed significantly during and after laryngoscopy and tracheal intubation in control group but remained unohange the baselin values in the group who received sufentanil. control group ecg suggested more changes than sufentanil group. conclusions: the results indicated that , mg/kg sufentanil for anaesthesia induction reducing the pressor response to laryngoscopy and tracheal intubation. obiective: the aim of this experimental study was to evaluate morphologically the influence of anesthesia in liver as well as in isolated hepatocytes (hc). methods: a total of female swine ( - kg) were used as liver donors and were randomly assigned to one of two groups regarding anesthesia protocol: group a (n= ): induction with intravenous sodium thiopental in a dose of mg/kg, group b (n= ): propophol in a dose of mg/kg for induction'and mg/kg/h for maintainance of general anesthesia. both groups were under the same preanesthetic regimen (diazepam, ketalar and atropin) and received standarised doses of fentanyl and pancuronium during anesthesia. in beth groups total hepatectomy was performed and the liver was perfused with - it of cold ( oc) university of wisconsin solution for a period of hours before hepatocyte isolation. liver tissue samples were fixed in formalin for the morphological study and stained with hematoxylin-eosin and pas. for hc isolation collagenase solution (type v, sigma, c- , . mg/ml) was infused via portal vein and the liver was incubated at oc for rain. cells were filtered and then washed in cold hanks' solution. isolated hc were fixed and prepared for staining or simply cryopreserved (- oc). results: histology was completed in / experiments ( in group a and in group b). mononuclear infiltration (halothane type injury) was found in all specimens ( / ). focal zonal necrosis and acidophilic bodies were found in specimens from group a ( / and / respectively) while portal inflammation with piece meal necrosis was found in one specimen from group b ( / ). smears of hepatocytes -beth formalin fixed and cryopreserved at - oc -were stained with hematoxylin-eosin and showed morphologically intact hepatocytes. conclusion: pre[imineq~' study of our material reveals mote frequent livet injury in the thiopental group, but this finding has yet to be established by increasing the number of observations. objectives: in this paper we present our experience and point out the importance of sedation of those patients who suffered severe head injuries/contusic cerebri with signs of decelebration/and who were put on ventilatory machine to obtain better mechanical ventilation in neurosurgical intensive care unit of emergency center in belgrade. methods: patients were treated from jan. till dec. results: in patients we successed to reduce agitation and decelebration. conclusions: the major demand of sedation in neurosurgical patients are that the patient should be calm, comfortable and painless. references we compared three analogous groups of patients in each, with orthopedic operations on lower extremities. in each group we applied different kind of analgesia: first group rece-ned local anesthetic ( ml . ~ bupivacaine) when analgesia was first demanded; second group received ml fentanyl via peridurai catheter when analgesia was first demanded, and third group received m] fentanyi intravenously on demand for analgesia. we used visual analog scale (vas) for estimation of pain intensity and success of applied therapy. statistical data analysis was performed using student's t-test. tha best vas had group in which local anesthetic was applied periduraly. second was the group with periduraly applied fentanyl, and third was the group with intravenously applied fentanyl the longest duration of the effect of analgesia ~/as in the second group. there were no adverse effects and complications, apart from mild sedation in the third group. for orthopedic operations on lower extremities, application of peridural catheter for anesthesia and successful postoperative analgesia with local anesthetic, or opioid analgesics is acceptable. background and obiective : tympanic temperature measurement (ttm) is a relatively new procedure which provides accurate estimates of core temperature in stable postoperative patients and in patients admitted to the emergency ward. however, experience with this technique in hemodynamically unstable adult icu patients is limited. design : prospective study with patients serving as their own control. se:ttijlg : adult medico-surgical icu in a tertiary care hospital. patients : consecutively enrolled patients with thermodilution catheters in place and without contraindieation for rectal temperature measurement and without hypothermia (core temperature < ~ interventions : tympanic temperature, measured by a commercialized tympanic thermometer (genius a first temp) was compared with pulmonary artery (pat) and rectal temperature (rt). within minutes, core temperature was assessed in each patient by the same trained individual using the three techniques in random order. measurements and main results : mean bias (ix~ and its variability (sdr of method comparison pairs were calculated using the methods comparison analysis as described by bland and alunan (lancet, ; i : - objective: to measure the prevalence of pressure sores on the intensive care unit and the effect of risk calculation on pressure score prevalence and pressure score severity. method:in during a period of months a series of prevalence studies was carried out on the sicu to investigate how many patient days with pressure sores were taken care for by the icu nursing staff, what kind of preventive interventions were done and what the patient risk was on developing a pressure score. results: on average there was a prevalence of pressure sores on the buttocks of . % on the short stay unit and . % on the long stay unit; preventive interventions increased when the pressure score was visible for the nurse and the majority of patients had a high risk or extra high risk for developing pressure sores according the pressure score risk calculator. as a result of these findings the nursing management decided in that nurses had to complete daily on every patient the pressure score risk assessment in order to be able to take adequate preventive interventions. when the results of the two studies were compared, the most important results were that: ) there is no indication of a reduction in patient days with pressure sores (short stay unit: %, long stay unit: %); ) there is a reduction in severity of pressure sores (grade iv decreased from . % to . %) because adequate preventive measurements are initiated by icu nurses in an earlier stage. possible explanations for the increase of patient days with pressure sores on the long stay unit are that the average pressure score risk score was increased from . to . and the mean frequency of nursing patients on alternate sides decreased from . to . times each day. conclusion: daily assessment of the individual patient risk on developing pressure sores does not decrease development but reduces the severity of the developed pressure sores. method: the conventional woundcare method of patients with an open abdomen is to change frequently the saline soaked ribbon gauze pads ( - times each day). this method is labour intensive for the itu nursing staff and rather uncomfortable for the patient. problems that often occur are: insufficient hygiene, frequent nursing interventions, a progressive risk for deterioration of the skin and underlying tissues, difficult to measure abdominal output and in case of bowel fistulas enteral feeding is hardly possible. in using the new method, stomahesive is applied on the skin surrounding the wound. a large size of surgical film dressing, opsite | is applied over the abdomen. two or more foley ~ catheters ch are inserted through an opening in the surgical filmdressing. the application of several lateral openings in the catheters is advised. the drains are held firmly in place between two layers of sterile opsite | "flexigrid ~'' x with the so called bookend method and are connected to a low vacuum suction system ( - kph) results: we studied the frequency of dressings changes on patients in the itu. in total they had days with an open abdomen. during this period there were dressing changes. this means one dressing change every days. further advantages of the new method are; more hygiene in patient care, no maceration and irritation of the skin, nursing on alternate sides is possible, output can be measured, in case of bowl fistula, enteral feeding is possible and an abdominal lavage is possible on the sicu by opening the opsite | conclusion: this new method of woundcare management is more patient friendly, prevents several nursing complications and decreases the work load for the nursing staff. objective: to investigate the interaction between the ventilator and the closed suction system related to possible induced negative pressure by this sytem. method: we studied in a testlung model what the effect was of the different ventilators (evita: dr~iger; servo c: siemens), ventilation modes ppv, simv) and ventilator settings (tv, trigger level, frequency, peep level) on the induced negative pressure by the closed suction system during suctioning. results: when using the evita the magnitude of the negative pressure increased when the ventilation frequency and tv decreased.. the largest negative pressure (- cm h ) was produced with a tv of ml and a frequency of /min in the ippv mode with trigger level on - cm h and a peep level of + cm h . the servo c showed a complete different pattern. the largest negative pressures were measured when no trigger level was set ( cm h ), the induced negative pressure was not depended on the tv or ventilation frequency but more depending on the ventilator mode. the simv mode produced the smallest negative pressures ( - cm h ) and the ippv mode the largest ( - cm h ). conclusion: the effectiveness of the closed suction system is very much depending on the kind of ventilator, ventilator mode and ventilator setting that is used. if the interaction with the used ventilator is not known by the icu nurse this piece of equipment can cause damage to the patient by inducing large negative pressure in the comprimised lung and there fore creating the possibility of alveolar collaps and atelectasis or oedema. introduction : ethical problems are daily and disturbing preoccupations for the icu staff. objectives : improving ethical management in icu by creation of an intelprofessional group of ethical reflexion ( iger ). methods : existing was evaluated by a preliminary formulated series of questions sended to the whole staff (q , n = , items) after two training sessions (laws, deontology, professional values, culture, norms of quality) followed by persons ( %) and directed by an external chairman, satisfaction and needs of the staff were evaluated by a second series of questions (q , n = , items). at the issue, iger was created. results : q : responders ( %). law's misinformation : to %, disagreement for limitation of intensive cares : %, hope to improve collective decisions and creation of iger : % q : responders ( %) : satisfied by the training sessions : %, non satisfied : %, want to continue the project : %, refuse : %. iger was constitute by physicians, nurses, secretary, dietetic (n = ). the first working theme was {< therapeutic's withholding and withdrawing decisions in icu ~>. four subgroups of iger's members (having access to an ethical library) worked independautly and submitted their reflexions in a tdmestrial plenary session of iger in the presence of an external chairman, allowing a synthesis. at the issue a report was writted to be used as a reference for bedside and individual decisions. conclusions : constitution of iger seems to improve ethical management in icu. the first result of iger is that it is now possible to began collectively a reflexion concerning therapeutic's withholding and withdrawing in icu. the work is going on and further subjects will be studied. objectives: ) to compare the value of heat-moisture exchangers with bacterial filters (hmef) and without bacterial filters (hme) in the prevention of colonization of ventilator tubing and ventilator-associated respiratory infections. ) to asses the temperature and relative humidity of inspired all using both types of heat-moisture exchangers. methods: mechanically ventilated patients were randomized, to either hmef or hme. endotraeheal aspirates, pharyngeal swabs and samples from tubing were collected for bacterial cultures on the st, nd day mechanically ventilation and weekly thereafter. temperature and relative humidity were measured in patients ( hmef and hme) h and h after placing the hme or the hmef. results: both groups were comparable as regards age, mechanical ventilation period, severity score (saps ii), leukocyte count, and number of patients with prior antibiotic treatment. from the hmef group, ( %) ventilator tubing yielded microorganisms in, at least, one sample as compared to ( %) of the hme group; p=ns. the incidence of respiratory infection was similar in both groups ( % vs %, p:ns, for hmef and hme respectively). among the bacterial species isolated from ventilator tubing in the hmef group, ( %) were not isolated from pharyngeal swabs. a similar ratio was shown in the hme group ( / , %). both heat-moisture exchangers were efficacious in keeping a good relative humidity of inspired air ( % • vs % • .%; p=ns, for hmef and hme respectively). relative humidity was significantly higher after h of mechanical ventilation in the hme group as compared to hme group ( . % • vs . % • %; p= . ). conclusions: both types of heat-moisture exchangers have the same effect on the prevention of colonization of ventilator tubing. similar relative humidities are achieved when using either type of heat-moisture exchanger. results: tumor and nontumer enhrgements of the thyroidea were present in ~ of the operated, surgicel adrenal disease in io!, hyperplssle or persthyroid gland tumor in ~ end endocrine pancreatic tumors in %. in the intensive oere unit, these patients wore screened by noninwsive monitoring in ~ of cases: and invasive monitoring was applied in % of ceses.the basic noninvesive methods included: electrocardiogram with standard end precerdial leeds, percutaneous eutomotlc measurement of systolic, diastolic and mean arterial pressure, measurement of hourly diuresis and body temperature, frequency, hearing capacity and rhythm of one s own breathbng bs well as pulse oxymetry. a special plece in monitoring and control of vital parameters in postoperative period belonged to the nurse, thoroughly trained for enelysis end interpretation of the observed parameters which would be discussed in the paper. it has been believed that the leader sits at the pinnacle of power. over the years, this has proven to produce frustruation and anguish instead of the expected results. leaders have not been able to produce the changes they know are essential to their organization's survival with this command-and-control paradigm. through literature reviews and evaluating leadership styles, one can clearly see the most effective form is that of empowering people to a new level of performance -not ordering it. changing the leadership paradigm to a manner/style that has been shown to be effective and one of people empowerment shifts the focus to personal responsibility for performance. removing obstae}es~ stimulating self-directed actions, and determining focus and direction are just a few elements used to create the successful environment of empowerment. with increasing pressure in the health care arena, it becomes critical that a leader's job is to get the people to be responsible for their own performance. developing ownership, creating an environment where people want to be responsible, being a mentor or coach, and learning faster while encouraging others to do so demonstrates the commitment to effective leadership. this presentation will illustrate the critical components that are achieved when every person in the institution is empowered to perform at a level that is directed toward positive, effective results. herrera m. (md) . icu. hospital regional. malaga. spain. the systems of veno-vanous continuous haemofiltration (wchf) have a high cost and a limited life span. in an attempt of lengthening their mean life it has been proposed to accomplish programmed washes of the ~-stems. this practice supposes an increase in nursing workload. in order to evaluate the real efficiency of this practice we have accomplished this study. material: prospective randomized study of all the filters of vvchf used during the last year in our icu. we have determined two groups of filters, in the first (group a) we accomplished washed in a programmed way, and in the other (group b) only when the alarms of the system suggested a clotting of the filter. for the statistical analysis we used the kaplan-meier test for survival analysis. results: we have studied a total of patient submitted to wchf during the last year. we used a total of filters with this results. objectives. sounding out the nurses about the need to inform patients" relatives and the rigth kind of such information, like a preliminary approach to an information cuality assessment, methods: we inquired all the nurses of the intensive care unit of an regional hospital by an semiestructurated questionary which included personal data: age, sex, contractual relation, professional experience.., and opinion data: do you think to inform relatives is a nurse task?. which of the next informafions do you think is more important?, please, write others topics about information you think are relevant. we process the data on epi-info estatistical program and use x test to compare the results. results" from nurses of staff refused to flu the quetionary, and were not available. of the remaining, %were v~men and % men. the mean age were . % had an svable contract and ( eventual, the mean professional experience were of years and % worked in the unit since more than years. the % answered that offer information to relatives is part of the nurse activities. we did not find differences with nurses who answered negatively comparing by sex, age, contractual relation or proffesional experience. the three information topics found out like more important were: ) to inform about patient mood. ) to inform about happenings from the last visit. ) to inform about dressing instrument required by the patient, nurses who answered negatively think that to inform is a doctors task or that nurses are not competent. conclusion~ intensive care unit teams (nurses, doctors and auxiliar personnel) should get accord on who and how to inform relatives, we consider the nurses' role on information as unquestionable. objective: investigate the respiratory and cardiovascular response after discontinuing oxygen therapy durir~ intr~/]o~pital transport. desiqn: fifty-one patients ( male and female, aged + , and , , years respectively, ~+sym) being on therapy were studied prospectively in two consecutive intrahospital transports. oxygen therapy was continued in the first transport while the second one was performed as usually, i,e, without . during transport each patient was monitored by pulse oxymeter and holter whereas arterlal blood gases were tested just before a~xl aft~-trar~portation. results: compared to daseline, pa and sa were signif~canthy decreased in the case of oxygen discontinuation (p< , i). paco was significantly inur~ds~i only in the subgroup of patients with obstructive lun[ disease (p< , ) . heart rate increased in all phases of the transport when administratlon was discontinued. blood pressure remained stable in either case. the percentage of supraventricu!ar extrasysto!es, ectopic v~r[hicui~r contractions and st-s ~ment depression was progressively increasing and became very high at the end of transport in the case of therapy discontinuation. other arrhythmias did not change significantly. conclusion: discontinuation of oxygen therapy during intrahospital transport causes severe drop of pao and sa , increases the heart rate and contributes to the appearance of arrhythmias which were not present before. methods:for evaluation of the functional state of brain the complex of methods was used,whieh included electro encephalngraphy ( brain mapping ), rheoencephalography, tetrapolar transtorax rheography. for the estimation of humoral status the level of histamine and serotonine, products of free-radical oxidation,enzimatic markers of ishemic damage of brain and of endogenous intoxication was investigated. results: patients with encephalopathies after resuscitation were observed.asystolia was as a result of:shock, trauma, asphyxia,poisonings,appiication of drugs, eclamp sia,injury of the heart,diseases of fhe cardiac vessels. all patients with postasystolic syndrome entranced in comafose condition.in the group (reconvalescents) the depth of coma by glasgo~ pittsburg"s scale was , +- , . the duration of coma was from rain. to hour,average , +- ,sh.ln the group (the deads) the depth of come was , +- , .the artificial lung ventilation was used in all patients:in the group , +- , days,in the ~ , +- , days.apallish syndrome developed in cases,in patients diagnozed <<brain death~. the th degree encephalopathy (coma) was found to be associated with disorganized eeg-pattern with predomi nant alpha-( group) and slow ( group) activity. the relative power of delta-and theta-ranges was about - per cent.the patients with apallich syndrome demonstrated greatly elevated theta-range power, that of beta -range was essentially decreased. the degree of disturbances of circulation in the both groups was different.cardiac index (ci) and stroke index (si) in the group decreased on , % and , z, in the -on , % and (; , %.general peripheral resistance (gpr) increased in the group on , %,in the -on (; , %.in the group brain blood flow was increased, in the -decreased on , n.in the group there was the normotonic type of reg-curve,in the -atonic or hypotonic type (without reaction on pharmacologic influ ence).disturbances of permeability of cellular membranes (enhanced free-radical oxidation with an increase in di enic conjugates on and n) and vascular ones (an increase of serotonin concentration on and %, hi stamine content on and %) resulted in hyperfermentia (an increase of concentration of creaune phosphoki nase in the group on %,in the - %.the level of middle molecules (mm) increased in the group on , %, in the -on , %,of polyamines (p) (spermidin,spermin,putrescin).coefficient of correlation between mm and p was , . immediate correction of neurocyte metabolism is impossible due to marked brain oedemaswelling,severe dis ordes of cerebral circulation, disturbances of membrane permeability.thus,the following treatment algorythm might be advisable: . protective inhibition of brain and reduction of its energy requirements. . recovery of cell and vascular membrane fuoctions. .recovery of blood circulatiom .oxygenation of nervous tissue and drainage of brain disintegration products.in patientshbo carried out. .active methods of detoxication (homo-and enterosorption). .correction of cerebral metabolism. . dehydrative therapy must be very cautious. conclusion: the activation of energetic metabolism in neurocytes must be carred out only under neurophysiolngical control and after definite preparation. ( ). the clinical estimation of acute cerebral failure carried out by olasgo-pittsburg"s classification of coma. we studied such groups of patients: poisoning co ( ), asystolia ( ), eclampsia ( ), acute renal failure ( ), control group ( ). methods: electroeneephalngraphy (brain mapping) was fulfilled by means of encephalograph <,medicor ~ in monopolar channels. the estimation of eeg patterns by zhirmunskaya method ( ) was carried out. there were analyzed and changes of eegb by results of rapid transformation furie after rhythmical photostimulation(phts) , , , hz. we studied also the figures of absolute and relative power in such diapason : delta ( - hz), theta ( - hz), alpha ( - hz), betal( - hz), beta ( hz and more). results: all eeo changes were divided into following types: -organized ( , groups); iii -asynehronic ( group); iv -disorganized with prevalence of alpha-waves ( , , groups); v -disorganized with prevalence of delta-and theta activity ( , , ; , groups) akkording to our model of hormonal-metabolic disbalance in pregnancy , one of the main reason of destosis is hypoergos , reesults in endotoxemia and neuro-endokrine disregulation. so, stady of central nervous system function give us the information about adaptation processes. the aim of our work is to study the degree of neurologikal deficit in destosis when olifen and lipin were used. there were studied pregnants with different severe forms of gestosis. the degree of neurologikal deficit was valued by datas of neurologikal status . eeg with ,~brain mappinng~, , electrikal resistance of the skin. the komplex inteensive therapy with applikation of olifen and lipin allowed to improve the patient,s condition , decrease the degree of neurolodikal deficit and mortality . kostenko v.phd,kabanko t.,phd,galalu s.md,beliavtseva n. ,shramenko k. phd intensive care department,donetsk medical university, donetsk, ukraine plasmapheresis (pph),as other extracorporal methods of detoxicatin,has a great importance in contemporary medicine. the role of pph is special,because of its simplicity, effectiveness, atraumatic.we incalcated pph in obstetrical clinic. there are rough changes in agregate condition of blood in more of pregnants.these changes lead to disturbances of central,organ and peripheral hemodynamic.the therapeutic effect of pph is due to influence on agregate condition of blood. we considered that application of pph is very effective in pregnants with:bronchial asthma, severe forms of diabet, psorias, gestosis, allergic diseases. we used the membrane pph in pregnants: apparatus-,,hemos-pf>,, plasmofllter pmf- ,with effective area- cm,the volume of extracorporal contour- ml.such pph has no the ~ agressive effect,,, as in cases of application another extracorporal methods. this method was incalcated in our practice recently, so results will be reported in further publications. ( ). post-operative cerebral neoplasm ( ), post-operative subdural hematoma ( ). icp was monitored via a catheter inserted in the lateral ventricle and values were continuously digitally recorded by means of a bedside computer data acquisition system (maclab). the fiberoptic tracheobroucosenpe, which guided the procedure, was passed between the nasotracheal tube and the trachea in order to avoid hypoventilalion. the patients had stable baseline hemodynaimcs. propofol infusion and fentanyl boli were administered to mantain stable mean arterial pressure values. peak (mean(sd)) icp duping the minutes pre-ciaglia procedure (baseline values) were compared with values during ciaglia procedure, and the minutes p st-ciaglia procedure. data were compared with repeated measures anova. results: ciaglia procedure duration was (mean(sd)) ( ) objectives: transient global amnesia (tga) is a syndrome caracterized by impairment of short-term memory, inability to form new memories, retrograde amnesia and repetitive queries, without other neurological signs and symptoms. the pathophysiology of tga is unknown; thromboembolic, epileptic, migrainous and metabolic mechanisms have been suggested. to address some of these issues, we undertook a study of cases of tga in whom we examined clinical, laboratory data, electroencephalogram, ct of the head, ultrasonography ecodoppler. methods: patients were included in this study: men and women. the mean age was years. all cases underwent a standard clinical examination, electrocardiogram, routinary humoral tests and x-ray, electroencephalogram (eeg), ct scan of the head, ultrasonography ecodoppler. results': the mean duration of amnesia was h. m. +/- h. m. hypertension was found in patients ( %), ischemic heart disease in patients ( %), hypercholesterolemia in patients ( %), hypertrigliceridemia in patients ( %), smoking in patients ( %), atrial fibrillation in patient ( %), history of epilepsy in patient ( %), migraine history was not recorded. ct scans of the head showed multiple small deep infarcts in patients ( %), a single hypodense lesion in patients ( %). in patients electroencephalogram was normal ( %), in patients there were widespread nonspecific electrical changes ( %), in patients there were focal nonspecific eeg abnormalities ( %). conclusion: in our study tga was more common in women ( %). we showed a prevalence of hypertension, hypercholesterolemia and cerebral infarcts compared to normal controls. we have demonstrated a higher incidence of nonspecific electrical changes in tga of lower length, while ischemic lesions in ct of the head were more frequent in tga of greater length. these data seem to be in agreement with the hypothesis that tga is a heterogeneous clinical syndrome, consisting of pure, epileptic, and ischemic types. however we did not find any correlation useful in discriminating pure from associated tga forms. from our study it is tempting to speculate that pure tga is a rare event, underlying still unknown mechanisms wich differ from ischemic, epileptic, migraineous causes. objectives: aneurysmal subarachnoid haemorrhage (sah) is special condition increasing intracranial pressure (icp) in various ways. at the other hand cerebral vasospasm and related delayed ischaemic deficit (did) could answer for the poor outcome. triple h therapy seems today a basic option to prevent did, but it may increase the icp worsening the altered intracranial pressure condition and thereby the cerebral perfusion pressure (cpp). is there any way to individualise the triple h therapy when it is necessary? methods: between sept. march thirty-seven patients with intracranial aneurysms were operated on within hours following sah. five patients were in hunt-hess iv at admission. all patients received triple h therapy in a preventive fashion following surgery and were monitored by daily transcranial doppler ultrasonography (tcd). icp and cpp was measured in twenty-four cases. twenty-two of them received lumbar liquor drainage (lld) and nineteen were administered induced hypertension. the other group was treated by basic triple h therapy. results: in group with monitored icp the outcome was twenty-one excellent, one poor, two died (one of them died from extracranial decease). in the other group four had excellent, six moderate, two poor outcome, and one died. conclusion: according to our recent observation the patients can be divided into two groups of therapy. in group i, the patients with elevated tcd values and either low or high icp reacted to lld. we are concerned that haemodilution and slight hypervolaemia should dominate in the triple h therapy. in group ii patients having high icp with tcd and/or symptomatic vasospasm should be managed by the induced hypertensionhypervolaemia dominated therapy focusing on cpp (icp) and focal neurological signs. air emboli were detected in lo% (n= ) of natients undergoing coronary srtery bypass craftin~ (cabg). central nervous system ~ysfunction occured in ~$ of the nstients with air embnli and in none of those ~ithhout air embo!i. hvtothermia is the classic form of oro-tect~on used dur~nc ~"~" " ~ ~ ca~.,~modu] :r, on~_,_. bj/oass. the surf~eon sho,;,ed thorough!~: evecnnte air from the heart, but the onesthesio!o[[ist can signifieamt!y influence the outcome by emt!oyin ~ methods to detect and treat air emboli. the changes in head rate are primarily due to alterations of autonomic tone. the heart rate variability (hrv), that express the degree of heart rate fluctuation around the mean heart rate, reflects somehow the condition of central nervous system. hrv may be measured by a number of techniques. short-term time-domain variables of hrv are reflect generally the vegal activity. in this study the changes in hrv variables of patients with brain damage, and in addition the changes in hrv measurements in comparison with the clinical evolution were evaluated. eight patient with brain damage and six normal individuals as control group were studied. a elecrocardiographer with availability of computation the sequence of beat-to-beat intervals for one minute was used. the following variables of hrv were measured: ) standard deviation (sd) of beat to beat r-r interval differences that reflects the respiratory control, )the maximum/minimum (max/rain) interval that reflect variability related to baroreflex and thermoregulation and ) the coel~cient of variation (cv), the results are shown in the in the patients with brain death and in vegetate state there were virtually no hrv. increased hrv pattern was found with clinical improvement, the changes of hrv precede of the changes of gcs, we conclude that time-domain hrv could reflects the degree of brain damage, it is good prognostic index of the brain damage and may change earlier than the gcs. objectives: cerebral co vasoreactivity is an important determinant of cerebral blood flow (cbf) and has been shown to be of prognostic value in head trauma (acta anaesthesiol. scand. ; : - ) . we wondered whether co vasoreactivity could be selectively altered in one hemisphere in comatose patients. methods: patients ( m/ f, age - yrs, glasgow - ) in coma due an acute brain lesion (trauma, hemorrhage, or infection) were studied. cbf was measured bilaterally using jugular thermodilution at paco , , , and mmhg by increasing pico with mechanical ventilation kept constant. normal co vasoreactivity was defined as an increase in cbf of at least i ml/min. g per mmhg paco . results: patients had normal co vasoreactivity bilaterally, patients had altered co vasoreactivity at both sides, and patients had a normal response at one side (left or right) with an altered response on the other side (dght or left). for the patients left cbf was in mean ! ml/min. g lower than right cbf (figure methods: following institutional approval piglets (body weight :tl . ) were anaesthetized by % fluothane. a catheter was placed in the right femoral artery for blood pressure monitoring and a fiberoptic catheter (oxymetncs- abbott) was advanced via the right internal jugular vein to the jugular bulb for sjo determinations. another catheter with a balloon on the tip was advanced in the right atrium via the right femoral vein. a mean arterial pressure (bp) at mmhg was achieved by appropriate balloon inflation for rain and two groups were cleated: i) the hypoxemic group by respirator disconnection (*) and it) the hyperoxemic group by fio =l on respirator (o). samples were obtained at time ( ), ' min at hypoperfusion ( ) arid at reperfijsion at ' ( ), ' ( ) and ' ( ). pao , pjo and oxidative brain stress evaluation was performed from jugular bulb blood. the latter included: i) no synthase (nos) and xanthine oxidase (xo) activities by a method based on the oxidation of scopoletin detected fluorometrically, it) no levels estimated as onoo-by luminol enhanced chemiluminescence in the presence of ~tm hydrogen peroxide (h ). resul'~s: the mean pao was mmt-ig for group i and methods: we retrospectively reviewed all upper gi-endoscopies, performed in the period january -july in patients ( men and women) admitted at the icu's of our hospital. results: it concerned surgical, medical, eardiological and neurological patients with a mean age of . yrs (range: - ). in %, the endoscopy was performed at the icu and in % at the endoscopy department. in % of the cases, the endoscopy was primarily diagnostic, of which % was performed for localization of upper gi blood loss. in % the endoscopy was primarily thempentic, of which % was performed for placement of a duodenal feeding canula. location of the upper gi bleeding was: variees ( %), duodenal ulcer ( %), oesophagitis ( %), gastric ulcer ( %), others ( %) and none ( %). as coincidental findings were noted: cesophagitis ( %), gastritis ( %), gastric deer ( %), duodenal ulcer ( %), duodenitis ( %), oesophageal ulcer ( %) and others ( %). conclusions: there were marked differences in indications and findings of endoscopy at the different icu's. these differences reflect an admission bias and differences in populations and treatment preferences. compared with cardiological and neurological icu's, substantially more endoscopies were performed at surgical and medical icu's. in a considerable number of cases, no source of upper gi blood loss could be found endoscopicaiiy. when upper gi blood loss was the icu admission diagnosis, the main cause was needing varices, which could be controlled endoscopically in the vast majority of cases. when upper gi blood loss was ndt the icu admission diagnosis, peigie ulcer and oesophagifis were the main causes of bleeding. because of the considerable number of coincidental almom~adities found at endoscopy, there is still room for debate whether antacid medication and/or motility stimulating agents should be given prophylactically at icu's. many studies have shown that blood lactate levels in survivors and nonsmvivors of traumatic and septic shock are significantly different. the degree of multiple organ failure is related to the duration of lactic acidosis ( ). the aim of this study was to evaluate blood lactate level as a prognostic marker of high risk postoperative patients who may benefit from invasive hemodynamic monitoring and aggressive fluids administration and early inotropic support based on oxygen transport parameters. methods: patients undergoing elective long term vascular and abdominal surgery (asa i-bi) were studied. blood lactate levels were measured after icu admission. in the case of blood lactate level above mmoltl, measurement was repeated every hours for hours or until normaiisation (blood lactate level less than mmol/ ). type of surgery, length of surgery, amount of fluids delivered intraoperatively and postoperatively, hemoglobin levels, hemodynamic variables, diuresis, postoperative complications, length of icu stay and clinical outcome were recorded. because no attempts were made to randomisr therapy or change our standard therapy protocol institutional approval was not required. rebuts: the frequency of postoperative complications was , % and mortafity was , % in a group of patients with blood lactate level less than , mmol/l (n = ). frequency of complications ( , %) was significantly increased in a group of patients with blood lactate levels , - mmol/l (n = ), mortality was , %. mortality ( %) and frequency of complications ( %) were significantly increased in a group of patients with blood lactate levels above mmol/l (n = ). conclusion: blood lactate levels can serve as early marker of high risk postoperalivr patients and may predict increased risk of postoperative complications mad ~e death. objective.~: investigated practicability and clinical value of the routine measurement of hepatic venous oxygen saturation (shvo ) after major liver surgery, as shvo is considered an indirect parameter for splanchthc and hepatic blood flow. methods: consecutive patients were included in this study after liver resections for primary or secondary liver tumors. patients suffered from liver cirrhosis (childs a). immediately after post-operative admission on the icu a pa-catheter ,was inserted under fluoroscopy via the right jugular internal vein into the hepatic vein contralateral to the resection area. hepatic venous and arterial blood samples were drawn every two hours. shvo was correlated to the clinical course, macro hemedynamics, abgs aug other established lab parameters. results: in out of attempts the catheter could be placed correctly. in four cases after right hemihepatectomy the left hepatic vein could not be intubated due to a dorso-lateral tilting of the left liver. this is also reflected in a significantly longer time of fluoroscopy for catheterization of the left hepatic vein ( . _+ % rain vs. . + . rain; p < . ). the procedure requires a total of between and minutes. relevant clinical complications were not observed except for short term supraventricular arrhythmias during passage of the catheter through the right atrium. hemodynamics and pulmonary function could be considered normal in all individuals at time of measurement. shvo showed a span from . % to . % with a mean of . % -+ . %. the following statistically significant findings could be obtained: (a) patients with liver cirrhosis showed a significantly lower shvq than patients without ( . % • . % vs. . % • . %; p < . ). (b) a negative correlation between shvo immediately after operation and the duration of intraoperative hepatic vascular occlusion could be observed (r = - . ; p < . ). this correlation could also be seen for the first post-operative hours (r = - . ; p < . ). (c) a negative correlation between shvo and the difference between arterial and hepatic venous lactate levels was found (r = - . ; p < . ). conclusions: the routine measurement of shvo appears to be a promising extension of post-operative monitoring after major liver surgery. it is a safe method easily feasible on any major surgical icu though relatively time consuming. a further validation of this method is necessary in larger studies. therapeutic recommendations on the basis of shvo findings cannot be given yet. methods: in cases after major liver resection, in which abnormally low readings of shvo suggested an impaired hepatic blood flow, pgi was applied at a dose rate of ng/kg/min. as shvo can be considered an indirect parameter for hepatic blood flow, the effect of pgi infusion on shvo was measured. moreover, the changes of macro hemodynamics and pulmonary function were monitored. results: before the application of pgi z mean shvo for all patients .was . % ( - - - ). in three cases without major structural alteration of the remaining liver tissue the continuous intravenous administration of pgi lead to a sustained increase of shvo z to an average of . % ( . - , ). the postoperative course in these three cases was uneventful. in two cases with compensated liver cirrhosis after hepatitis c no change in shvoz under pgi infusion could be observed. both patients died and days respectively after operation in protracted liver failure. side effects of pgi included a slight decrease of systemic and pulmonary vascular resistances. consequently map decreased by up to % as did intrapuimonary right-left shunt increase. in none of the observed patients did these side effects posed a limitation of continuous application of pgi z. conclusions: in patients without structural alteration of the liver the systemic application of prostacyclin at a dose rate of ng/kg/min could significantly increase an abnormally low hepatic venous oxygen saturation after major liver resections, tn two cases of severe liver cirrhosis a similar increase could not be observed. after first clinical investigations and with the results of recent studies in animal further controlled clinical studies of prostacyclin in the postoperative management after liver surgery appear justified. any delay in gastric emptying can promote micro-aspiration and give rise to ventilator associated nosoarnnial pneumonia. h -receptor antagonists have been suspected of promoting pneumonia by changing the gastric ph. in a few tri',ds on humans ranitidine was noted to delay gastric emptying. the aim of this prospective, randomised, blinded study was to evaluate in a ventilated icu population if there was a difference between cimetidine (c) and ranitidine (r) on the gastric filling index (gfi conclusion: in this population there was no difference in gfi between c and r; however the age and creatinine were significantly different and could have favoured the c group. also the very long t/ could have hidden smaller differences between c and r as has been described in volunteers. between april , and april , , patients with severe acute pancreatitis were admitted to participating hospitals. patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (imrie score >_ ) and/or computed tomography criteria (balthazar grade d or e). patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). all patients received furl supportive treatment, and surveillance cultures were taken in both groups. results: fifty patients were assigned to the selective decontamination group and were assigned to the control group. there were deaths in the control group ( %), compared with deaths ( %) in the selective decontamination group. (adjusted for imrie score and balthazar grade: p = . ). this difference was mainly caused by a reduction of late mortality (> weeks) due to significant reduction of gram-negative panreatic infection (p = . ). the average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < . ). failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients ( %) and transient gramnegative pancreatic infection was seen in one ( %). in both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria. reduction of gram-negative colonization of the digestive tract, preventing subsequent pancreatic infection by means of selective decontamination, significantly reduces morbidity and mortality in patients with severe acute necrotizing pancreatitis. ieco by sodium hypochlorite (nacio) infusion is considered to be a model of microsomal oxidation in liver on cytochrome p- . active c provides oxidation of toxic metabolic products in the blood and exfused during plasmapheresis plasma, and also hydrophobic to hydrofilic transformation of substanses. sterile nacio in necessery concentrations was obtained by electrolysis of saline ( , - , % naci solution) in electrochemical set e~io- (russin,moscow). methods: . the nacio in concentration ragfl ( - ml/ h ) was administred into central veins in patients with extensive peritonitis and endotoxicosis - /t. erytrocytes resistance to nacio, circulating blood volume glycemia and hemostasis were initially estimated. . after plasmapheresis exfused toxic plasma was mixed with nacio conccantration of i mg/t in : ratio in sterile "hemacons".the effectiveness of plasma detoxication and possibility of its reinfusion were evaluated by determination of albumin effective concentration (eca g/l), the concanlration of medium molecular oligopeptides (mm , ) and other biochemical tests (bilimbin, creatinine, carbomide and so on). results: . the intravenous administration of nac excels detoxicative effect of hemosortion by - % provides effictive presentation of protein components and blood cells and improves the transport function of albumin by %. . the return of exfused plasma after its purification ieco was - %. only the remaning - % of deficient plasma were compensated by fresh cryoplasma and albumin solutions. ischemic hepatitis (ih) is a severe complication in critically ill patients. acute circulatory failure of multiple etiology can lead to splachnic hypoperfusion and cause acute and reversible anoxic damage. over a period of mos pts, m and f, mean age + . yrs developed liver disease compatible with ih. eight pts had a documented hypotensive episode (six pts with septic shock and two hypovolemic shock), while cardiogenic pulmonary edema in the absence of hypotension was responsible for ih in the remaining four pts. all the pts had a rapid striking elevation of ast, &lt and ldh with equally rapid resolution of these parameters to near normal wimin days (mean . ). the mean peak level of ast, alt and ldh was iu/l (range to ), iu/l (range to ) and iu/l (range to ) respectively. serum total bilirubin levels rose transiently with a moan t:eak level of . mg/dl (range . to . ), while altered coagulation paran-,ete's (pt> . times normal) was observed in four pts and clinically significant coagulopathy with fibrin degradation products occurred in one pt ( . %). renal impairment (cr> . mg/dl) was manifest in all pts; six pts developed non-oliguric renal failure ( %) while two pts required hemodialysis. ten lots required vasoconstrictor inotropes [dobutamine (range - pg/kg/min) and dopamine (range - pg/kg/min), while replacement of circulatory blood volume was performed in two pts with hypovolemic shock. eight lots expired ( . %), but none died as a direct result of hepatic damage. the mortality rate was higher among pts with concurrent renal failure ( %). it is concluded that: ) ih is not uncommon complication in the icu with the prognosis depending on the underlying disease. ) clinically significant coagulopathy is uncommon complication of ih. ) titration of inotropes is required to obtain optimal cardiac output support and subsequently liver blood flow. it is difficult to ascertain the perfusion of free flaps such as jejunal loops after surgery. objectives: to assess ischaemia as evidenced by intramural ph of jejunal free flaps used for reconstructive surgery following total pharyngolaryngectomy. methods: the sigmoid ph tonometer ( tonometrics inc.,usa ) was used to monitor intramural ph of the jejunal free microvascular flaps ( phig ) in patients who underwent total pharyngolaryngectomy. a standard general anaesthetic was given and all patients were admitted to the icu for controlled ventilation and monitoring. all had similar postoperative care. phig was measured pre, post-revascularization of the flap and on icu admission, , and hours postrevascularization. objectives: to classificate the wide spectrum of itc of anp into distinct pathophysiological patterns according to presentation and course. patients (pts) and methods: pts, ~( , %), ( , %) were admitted in the icu because of anp and acute respiratory failure(arf), ilean age: , • years. hean stay in icu: , • days. pts were operated, of them twice. hean value of ranson's scale: , • ( - ). we analyzed hemodynamic measurements,arterial blood gases(abg), x-ray findings(xrf), ct-scans and operative records. results: patterns of pleuropulmonary complications were identified: a)early hypoxia without xrf - pts. b)early ards with typical xrf - pts( died), c)early arf with xrf(atelectasis,infiltrates)- pts( died). d)late ards with typical xrf- pts( died), e)pleural effusions in various combinations with the above patterns - pts. overall mortality rate: / = , %. conclusions: l)frequent x-rays and abg are important for the classification of itc of anp. )even though patterns of classification in anp are not clearly distinguishable,they facilitate an anticipatory management. )deterioration of abg and xrf indicates that preventive measures for arf must be intensified and agressive surgical therapy is required. )delay of surgical therapy is related to worse prognosis(p<o, ) and prolonged hospitalisation time(p<o,ol). in the contrary, the early timing of the operation before infection and extrapancreatic necrosis is essential for a better prognosis (p<o, ). objectives: the development of cholestasis during intensive care treatment is allied with an inferior prognosis. this study investigates the sensivity, specification and also the positive and negative forecast of patients survival -exemplary for bilirubine. methods: during a period of months all surgical patients on icu were registrated prospectively (n = ). for documentation of disease development a standard foldcrform based on a computer-data-system was used. the results of this kind of documentation showed aapprax. , m!ll. of single patient informatioas. results: of patients didn't suffer from liver disease or have any operation on liver or bile tract. of them have had a normal scale of bilimbine in the postoperative period, a higher scale of bilirabine was regisu'atcd by patients. at a ,,cut-off" of rag% (total-bilirubine) the sensitivity was , , specivity , , positive predicive level , , negative predictive level , for survival criteria of a patient. the max. reached level of bilirubine, also the daily increase turned out almost the same results as they were found for other parameters nf cholcstasis like ap or gamma-gt. objective: the aim of this experimental protocol was to evaluate the morphological and functional parameters of isolated pig liver grafts, perfused in an extracorporeal liver support system. methods: the system consists of the graft liver, a membrane oxygenator (oxygenation surface . cm z, flow= itlmin), a heater, a centrifuge pump and a fluid reservoir. twenty pig livers, mean weight gr (min , max gr) were obtained and after a mean cold ischemia time of min were perfused fo} a mean of . h (min . , max h). perfusion solution consisted of r/l and hemacell. inflow to the graft liver was performed through the portal vein at a mean pressure of ( - ) mmhg at ~ while outflow was secured through the suprahepatic inferior vena cava. during perfusion the following parameters were evaluated through pre-and posthepatic hourly (to-t ) sampling: po , " + + " pco , ph, hco -, na , k , ca , osmolality, glucose, lactate, ast, alt, alp, u bilirubin and coagulation factors i, v and viii. biopsies were obtained periodicallty. b_p_~: results were as follows: mean ph fell from . at t o to . at t while mean output po fell from at t o to at t . mean output ast values increased from at t o to > at t while mean output alp values increased from . at t o to at t . mean output k + values increased from . at t o to > at t . histology revealed lesions of ischemic necrosis, more prominent after t . conclusion: results show that the isolated liver graft presents satisfactory function and morphology at least for a five hour perfusion period in the described extracorporeal circuit. correction of ph contributed to an increase in bile flow. between and the practice of transplantation has changed drasticaily in switzerland -besides kidneys also hearts, heart and lung, lung, iiver and pancreas transplantation has started in several centers. major information efforts have been made, organ exchange rules were set up and a national coordination center was initiated. the aim of this retrospective single center study was to assess the influence of transplantation on organ donation. in the past eleven years organs were donated from potential donors i single, multi organ donations) analysis of refusal was evaluated categorized into medical and/or familiar reasons. the number of potential donors increased from ( ) ,to ( ) with a concomitant drastic reduction of donations from % in to % in ; amounting to a net unchanged number of donations over the last years ( = ; = ) . the import and export of donor organs was balanced since the introduction of the national coordination center. in contrast multi organ donation increased from % in to % in despite of the more stringeant selection criteria, in conc]usion the introduction of a full range of transplantation procedures at several new university programs and the increase of multi organ donation has not had the forecasted impact on organ donation despite a sustained informative and promotional campaign, objective: monitoring hepatic venous oxygen saturation (svho ) provides online information about hepatic-splanchnic oxygen supply-demand ratio [ ]. previously, x~ reported hepatic venous catheterization in patients undergoing orthotopic liver traru~lantation (olt) [ ] . in the present study, we assessed the effects of nitroglycerin (ng), a vasudilator that affects the venous capacitance vessels more than arterial vessels and prostaeyclin (pgi , flolan r~, wellcome, uk), an arterial and splanchnic vasodilator on hemodynamies and hepatic venous oxygen saturation (svho ) in human liver transplantation. methods: with institutional approval and informed consent, consecutive patients, mean age - -_ years, were studied following olt. postoperatively, fiberoptic pulmonary artery catheter was inserted into the right hepatic vein. timed infusions of ng at a rate of . gg/kg/min and pgi at ng/kg/min were initiated for a rain period. each sequence was followed by baseline therapy for rain. results are expressed as mean=tsd. statistical analysis was performed using friedman's-two-way-anova-test, significance was accepted at p< , . results: ng at . gg/kg/min induced a decrease of mean arterial pressure (map) ( _ [baseline] vs. + mmhg) and pulmonary artery wedge pressure (pcwp) ( j: [baseline] vs. : mmhg). cardiac index (ci) ( - vs. + l/rain/m ), oxygen delivery index (do i) ( -+ vs. + mgnfin) and svho ( _~ vs. -l-_ %) were decreased (p< . ). pgi at ng/kg/min induced a reduction in map ( • nm~. _g) and pcwp ( + mmhg). ci ( _+ l/rain/m ), do i ( : ml/min) and svhoz ( + %) were increased (!o< . ). vasedilatation induced by ng decreased systemic oxygen supply and impaired splanclmie oxygenation. pgi increased systemic oxygen delivery in parallel with svho , suggesting a corresponding improvement of hepatic-splanchnic okygenation. thus, if vasedilator therapy is indicated in th orient receiving liver grafting, pgi appears to be advantageous. however, due to its platelct aggregation inhibiting properties, the usefulness and safety of pgi in olt patients has still to be determined. objectives: to analyze the effect of steroid treatment given to donor on the early function of transplanted kidney. methods: from january, until now donors were involved into this prospective study. every other donor was treated with mg/kg solu-medrol one hour before organ retrieval. according to the steroid treatment of the donor the recipients were divided into two groups: group -steroid pretreatment goup (y~= ), and group -control group (n= ). the donors and the recipients were treated using the same kidney transplantation protocol onl~r the adults, and the first cadaver kidney transplanted patients were involved into the study. the daily routine parameters were analyzed pre-and intraoperafive, and on the - th, th and th postoperative days. results: we could not show any clinically important differences between the two groups in respect of donor parameters. preoperative, the patients in group had slightly lower ereatinin level ( -+ g.,non vs. -+ gmol/ ) which persisted into the early postoperative phase. the values of the other examined pre-and intmoperativc parameters were almost the same. during the first postoperative days the patients in group i needed less diuretics (furosemide and renal dose of dopamine) and their sodium excretion was closer to the physiological range than in group . the other parameters did not differ significantly. the less furosemide need in group ! pe~isted to the end of the first month. conclusions: according to our data the steroid treatment of the donors improves the early function of the transplanted kidney in some respects. to prove the real benefit of the donor steroid treatment needs more data and further analysis. objectives: severe infections may compromize the outcome of liver transplantation..determination of new parameters may increase the knowledge of pathophysiologic mechanisms and may lead to changes in postoperative therapeutic management of patients at risk. methods: between august and september , patients with transplants were monitored for cytokines and extracellular matrix pammeters on a daily basis. serious infections (n= ) included microbiologic evidence and more than secondary organ failures. patients with cholangitis (n=ll) or uneventful postoperative course (n= ) referred as control groups. results: -year patient survival was . % ( / ): patients died due to serious infections, while died for other reasons. mean bilimbin, stnf-rii-, ifn- -, il- -, il- -, il- -, laminin-and neopterin levels were significantly elevated in patients with serious infections compared with patients experiencing mild cholangitis or with an uneventful postoperative course. a further increase of all parameters was observed in patients who subsequently died; tnf-ri/: _+ pg/ml vs • pg/ml; ifn- : _+ pg/ml vs . -+ . pg/ml; il- : -+ pg/ml vs -+ pg/ml; il- : -+ pg/ml vs _+ pg/ml; il- : _+ pg/ml vs • pg/ml; laminin: -+ ng/ml vs -+ ng/ml; neopterin: _+ nmol/ vs _+ nmolb for non surviving vs-surviving patients. a significant decrease of sialic acid yeas observed in patients with serious infections; and a further decrease occurred in patients who subsequently died: -+ mg/l vs • mg/ . conclusions: the increase or decrease of various cytokines and extracellular matrix parameters may be indicative for severity of infectiolx routine monitoring of these parameters may improve current diagnostic tools and poss~ly lead to changes in therapeutic management of patients at ~k. objectives: evaluation of the cytokine network after liver transplantation may give some insight in pathophysiologic mechanisms of rejection and may lead to detection of patients at high risk. methods: patients with transplants were monitored for various cytokines on a daily basis between august and september . rejection was assessed by histology in combination with clinical signs of rejection and laboratory investigations. results: during the first postoperative month, patients ( . %) developed rejection; patients were successfully treated with methylprednisolone (steroid-sensible rejection), while further patients required additional treatment with fk or okt (steroid-resistant rejection). patients subsequently developed chronic rejection. mean levels of various cytokines and extracellular matrix parameters including tnf-rii, ifn- , il-ib, il- r, il- , il- , il- , hyaluronic acid and neopterin were significantly higher in patients with steroid-resistant than in patients with steroid-sensible rejection. a further increase of some parameters was observed in patients who subsequently developed chronic rejection; bilirubin: . -+ . mg/dl vs . -+ . rag/all; tnf-rii: -+ pg/ml vs _+ pg/ml; il- : +- pg/ml vs -+ pg/ml; neopterin _+ nmol/ vs -+ nmol/ ; hyaluronic acid: _+ ~tg/l vs _+ ~tg/l for patients with chronic versus patients with acute steroid-resistant ~ejection. sialic acid levels decreased in patients with acute steroidresistant rejection; and a further decrease was observed in patients who tieveloped chronic rejection: _+ mg/l vs _+ mg/ . ~onclusions: various cytokines and extraeeuular matrix parameters were indicative of severity of rejction. the extensive increase of bilirubin, tnf-ii, il- , hyaluronic acid and neopterin may indicate subsequent chronic ection. monitoring of these parameters may, therefore, lead to changes in immunologic management after liver transplantation. background : combined kidney and pancreatic transplantation is being performed with increasing frequency in patients with diabetes mellitus and renal failure, as it offers more chances of success and better results than kidney transplantation alone. mycotic arterial aneurysm constitutes a devastating complication following pancreatic transplantation. all cases of mycotic arterial aneurysms have been however reported with exocrine pancreatic drainage into the gastrointestinal tract. intervention : we describe a series of consecutive whole kidney-pancreas transplantation performed at the university of geneva hospitals ( beds) between december and may . exocrine pancreatic drainage into the bladder (epdb) was performed to improve early detection of rejection episodes. epdb was hypothesized to reduce the risk of contamination from the gastrointestinal tract and the subsequent possible occurrence of potentially fatal infectious complication. in all patients the dual transplantation was performed through a median incision according to the procedure described by nghiem. results : two out of the patients who received kidney-pancreatic transplant developed arterial mycotic aneurysms and days following surgery. aneurysms developed at the site of the arterial anastomosis used to rearterialize the homograft. both patients had peritonitis caused by candida albicans requiring surgical drainage and intravenous antifungal therapy. rupture with hemorragic shock occured in both patients leading to graft removal in one patient, and three episodes of lffetreateniug hemorragic shock followed by graft failure and removal days after transplantation in the other. conclusion : arterial mycotic aneurysm constitutes an early, lifetreatening complication of kidney-pancreatic transplantation; it mandates graft removal. although exocrine pancreatic drainage into the bladder consitutes a definitive advantage for caller diagnosis of graft rejection, it does not eliminate the risk for retrograde colonization and subsequent severe infection in our experience. s. bocharov, i. teterina, regional clinical hospital, irkutsk, russia acute profound loss of blood can result from the very different injuries and hepato-pancreato-duodenai operations enter such a rank. ill-timed and inadeguate correction of operation hemorrage is one of the reasons for postoperation complications, including polyorganic insufficiency. the pathogenesis seems to be very complex. in early stages of bleeding the liquid enters the vessel bed, followed by hypoproteinosis and hematocrit fall. however, as decompensation develops, the fluid leaves the vessel system in the result of increasing postcapillary resistance and lowering col-ioidnooncotic blood pressure (cop). the resulting hypovolemia causes primarily acute disturbance of central hemodynamics and then of microcirculations and transcapillary exchange. central hemodynamic failure after acute loss of blood manifests itself through cardiac output lowering and capillary blood flow deceleration. taking into consideration, that % is critical value for cpv loss and for cev it is %, we consider arising the level of cop to the immediate task. cop raising allows to normalize transcapillary exchange, which we assess through cop and mcp (mean capilary pressure) gradient. the next task is to make up for globular volume till homeostasis providing level. considerable attention is given to catabolism inhibition and maximum possible enegry provision. control over high proteolitic activity of blood and callicreinkinin system activity implies direct proteases inhibitors. reologic, membrane stabilizing, antihypoxanthine and anticoagulant therapies are obligatory. virehow clinic, dept. of surgery, humboldt university berlin, germany regarding a high mortality up to % of fulminant hepatic failure orthotopic liver transplantation seems to be the only promising therapeutic approach in many cases. this study shows experiences from a transplantation center. between june and april patients suffering fulminant hepatic failure were admitted to our surgical intensive care unit all patients showed severe liver dysfunction with grade ii to iv encephalopathy. after a period of diagnostics and conservative treatment ranging from few hours to days (mean . days) we reported of these patients as possible organ recipients to eurotransplant. all of these patients were transplanted within hours, ( %) of them even within hours. the principal aetiologies were hepatitis b ( ), hepatitis c ( ), nanb hepatitis ( ), mushroom poisoning (amanita phalloides ). after transplantation patients suffered from initial-non-function and underwent re-transplantation. the one-year-survival rate was %, patients died within months after transplantation due to various reasons. patients were not referred for liver transplantation. of them never met transplantation criteria, improved by conventional therapy and could finally be discharged from hospital. the known reasons for liver failure in this group were mushroom poisoning ( ), paracetamol intoxication ( ) and fulminant hepatitis a ( ). patients suffering from fulminant hepatitis ( ) or intoxication ( ) were excluded from emergency liver transplantation for various contraindications. of these patients ( %) died despite conventional intensive care. we don't know if some of the patients in the transplantation group would have survived without transplantation, because whenever we decided on transplantation we could perform the operation within hours. but the good survival rate in the transplantation group ( %) the % recovery rate in the group, where there was no transplant-indication in our opinion and the fatal outcome ( % mortality) in patients with contraindications are an encouraging proof of a successful therapeutic strategy in acute liver failure. these results are based on a close cooperation between experienced transplant surgeons, hepatologists and intensive care doctors, using sophisticated laboratory and imaging techniques in a specialized center. introduction: during brain death patients suffer from multiple endocrinologic disturbances. one of the most important are those related with thyroidal axis. it is well described the euthyroid sick syndrome whose more frequent pattern consist of decreased triiodothyronine (t ), increased reverse t (rt ) with normal levels of tetraiodothyronine ( " ) and tsh, this lacking in " " levels lead to a change from aerobic to anaerobic metabolism which results in tissular damage. objective: .to study thyroidal pattern in brain death patients potential organ donors. .to avoid organ impairment by administration of t . .to study the hemodynamic and hormonal changes after the administration of t in these patients. material and methods:population: brain death patients of any etiology potential organ donors admitted to the intensive care unit. patients were classified in hemodynamically stable (group ) and unstable (group ). group received a bolus of . p.gr/kg. and a perfusion at a dose of - . p.gr]h of t . hormonal assays: total t (tt ), total " (tt ), tsh. fxee t (ft ), free " (ft ) and rt were determine at the moment of clinical brain death ( hrs) and in group two these assays were repeted at hours , and . results: patients ( male) with a mean age of years (range to yrs.) were studied. the clinical brain death was confirm later with other explorations (eeg, doppler). there were patients in group ( , %) and patients in group ( , %). hormonal pattern: at the moment of brain death tt was normal in cases ( , %) and decreased in i ( , %); tt was normal in patients ( , %) and decreased in ( , %); ft was normal in cases (i , %), decreased in ( , %); fl' was normal in patients ( , %) , decreased in ( , %) .rt was normal in cases ( , %) and increased in cases ( , %). there were no statistically significant differences in hormonal pattern between the two groups. only t levels at hours , and were significant in group . in the cases with ft decreased, the tt was normal in ( %) and decreased in ( %), tt was decreased in ( , %) and normal in ( , %), tsh was decreased in i ( , %), normal in ( , %) and increased in i( , %) and ft decreased in ( , %) and normal in ( , %) and rt was normal in ( , %) and increased in ( , %). there were no statistically significant differences in cardiac index, vascular resistances and pulmonary shunt before and after the administration ef t . conclusions: . the hormonal pattern most often find in brain death patients was: normal tt , decreased tt , normal tsh, decreased ft , normal fr and normal rt . . there were discrepancies in the values of ft and tt . there were no statistically significant differences in hemodynamic and pulmonary parameters. objectives: magnetic resonance angiographie (mra), a non-invasive procedure, provides flow-related information additionly to the anatomy of the vascular system. measurement of signal intensity and edge detection of vessel structures permits to calculate blood flow velocity and vascular diameters. we examined whether cerebral hemodynamic changes by altering the arterial pressure of carbon dioxid (pace ) could be detected by mra. methods: following institutional approval and informed consent, mechanically ventilated patients without elevated intracraltial pressure underwent mra with defined periods of hyper-, hypo-and normoventilation (pace : , , mmhg; arterial blood gas probes; avl). mra was performed with a . tesla magnetom (vision, siemens). two different mra techniques were used: a conventional time-of-flight- d-angiography (tr: ms; te: ms; fl: deg; slab: mm) for vessel diameter detection and a flash- d-gradient-echo-sequence (tr: ms; te: ms; fl: dog) for measurements of blood flow velocity. an axial view parallel to the ac-pc-iine (anteriorposterior-commissur-line) was used for repeated imaging of identical regions of interest toi) of the proximal part of the internal carotid (ica) and middle cerebral artery (mca) as well as of peripheral branches of the mca and the posterior cerebral artery (pca). results: changes of pace correlated with changing signal intensities, whereby under hyperventilation a decrease of , % (p . ) and under hypoventilation an increase of . % (p . ) was observed compared with normoventilation. blood pressures were stable throughout the whole study period, pace dependent changes in vessel diameters were more pronounced in peripheral branches of mca and pca. a change from normo-to hyperventilation produced a decrease in proximal vessel diameter of - . % (p _< . ) and in peripheral diameter of - . % (p _< , ). a change from normo-to hypoventilation produced an increase in proximal diameter of + . % (p < . ) and of + . % (p -< . ) in peripheral diameter. conclusions: pace related changes of cerebral vessel diameter can be easily detected by mra without injecting a contrast agent. the results confirm that co -reactivity is more pronounced in peripheral cerebral vessels, which are subjected to greater changes in diameter than major basal arteries. hyperventilation leads to a decrease and hypoventilation to an increase in signal intensity thus reflecting the corresponding changes in blood flow velocity, intensive care unit (icu) of "kat" hospital, athens, greece, ob!ective$; the value of bronchoscopy in pulmonary atelectasis of icu patients is under question the presence of an air bronchogram sign in xrays, which is considered as evidence of central bronchus patency, is referred in several studies as a negative criterion for bronchoscopy, whereas its absence as a positive one. it is also referred that air bronchogram sign correlates with delayed resolution of atelectasis, probably because of obstruction of many periferal airways (not central). the purpose of this prospective study was the evaluation of the air bronchogram sign on frontal chest film as a negative criterion for bronchoscopy and as criterion of delayed resolution of atetectasis, methods: icu patients with atelectasis were studied prospectively. they underwent bronchoscopy, bronchoscopic findings, presense of air bronchogram sign, and outcome of atelectasis were recorded, correlations were made, between: ) bronchoscopic potency of airways and air bronchogram sign } resolution time of atelectasis and broncoscopic potency of airways. ) resolution time'of atelectasis and air bronchogram sign, methods of statistical analysis were the t-student test and the chi square test, results:the patients were , men women , seventeen patients had atelectasis of whole lung, of upper lobe, and of lower lobe. ten patients had atelectasis in right and in left lung. eight from patients had air bronchogram sign in x-ray, there was no statistical correlation between air bronchogram sign and bronchoscopic potency of airways [ from patients with air bronchogram sign ( %) and from without air bronchogram sign ( %), had bronchoscopic potency of airways, p> . ], resolution time of atelectasis didn't correlate statistically with bronchoscopic potency of airways (mean resolution time in patients with bronchoscopic potency , days and in bronchoscopically closed bronchi , days, p> , ). there was also not a statistical correlation between resolution time of atelectasis and air bronchogram sign (mean resolution time in patients with air bronchogram sign , days, and without air bronchogram sign , days. p> ). conclusion~i; the presense of an air bronchogram sign in x-ray of icu patients with atelectasis, does not coexist obligatorily with bronchoscopic patency of airways and cannot be used as a negative criterion for bronchoscopy, neither as a criterion of delayed resolution of atelectasis. th. wertgen chest sonography (cs) is routinely used in our department to examine icu patients with clinical symptoms of pulmonary embolism, pneumonia, pleural effusion or unclear chest pain. we perform cs with a sector transducer ( . mhz) and a linear transducer ( . mhz) using acuson xp/ c. the sonographic signs of pulmonary embolism and infarction are most well demarcated, mainly wedge shaped and triangular pleural based lesions, more roughly structured, observed with a hyperechoic reflex in the center corresponding to the bronchitic (fig. ) . pneumonia is characterized by homogenously hypoechoic, wedge shaped parenchymal lesions, containing air or fluid bronchograms; they move with respiration (fig. ) . pleural effusions are spaces of various echogenicities, from anechoic to homogeneously echogenic, which may contain floating strands or complex septa, located between visceral and parietal pleuras (fig. ) . from march to april we did examinations by cs in icu patients ( male, female; age from - ). patients examinations pulmonary embolism pneumonia pleural effusion us-guided thoracic punctions were performed in patients. in two patients we found pneumonia or pleural effusion caused by a lung carcinoma. another two patients showed a normal cs (diagnosis: inflammation of the gall bladder, inflammation of the myocardium). conclusion: cs is a very useful method for icu patients with chest diseases. it takes less time and is less expensive than ctand sometimes of a higher diagnostic value than x-ray. last but not least cs is invaluable for the icu patient, because the examination is done save and quickly at bed side and the results of cs are very helpful in diagnoses and treatment. results : inter-observer reliability was evaluated as an % concordance. results of the tee classification were : class : n = ( %) ; class : n = ( %) ; class : n = ( %) ; class : n = ( %) class : n = ( %). therapeutic implications of tee in class patients were : cardiac surgery in patients (two cases of acute mitral regurgitation, two valvular abscesses and one hematoma compressing the left atrium), discontinuation of peep in one ventilated patient with an atrial septal defect, weaning of mechanical ventilation in one patient with an atrial septal defect, prescription of antimicrobial therapy in patients with endocarditis and prescription of anticoagulant therapy in patients with left atrial thrombus. the only noteworthy complication was a case of spontaneously resolving supraventrieular tachycardia. conclusion : tee is safe and well tolerated, and is useful in the management of icu patients with shock, unexplained and severe hypoxemia or suspected endecarditis. the aim of this study was to determine whether ultrasound guidance can help interns to improve the results of jugular vein access in icu. methods : in a prospective and randomized study, we compared, in patients admitted to the icu, an ultrasound-guided method (ultrasound group : patients) with an external landmark guided technique (control group : patients). all jugular vein accesses were performed by young interns with an experience of < procedures. results : internal jugular cannulatian vein was aci~ieved in all patients in the ultrasound group and in patients ( p.cent) in the control group (p < . ). average access time was longer in the control group ( • sec. vs • see. ; p = . ) and puncture of the carotid artery occurred in patients in each group (p = . ). patients ( p.cent) in the ultrasound group and patients ( p.cent) ia the control group (p < . ) were cannulated in rain. or less. the cannula was therefore unabie to be inserted within minutes in patients in the control group, with failure of eannulation in of these patients ( p.cent). failure was due to thrombosis (n = ), small calibre of the internal jugular vein (< ram) (n = ), abnormal vascular relations (n = ) or cervical irridation (n = ). among the primary failures of cannulation, an internal jugular vein catheter was able to be inserted in cases by an experienced physician on the side initially selected and with ultrasound guidance in cases. the catheter was inserted into the contralateral internal jugular vein under ultrasound guidance in the remaining cases. jugular cannulation was obtained at the first attempt in p.cent in the control group and p.cent in the ultrasound group. conclusion : ultrasound guidance improved the success rate of jugular vein cannulation by inexperienced operators in icu patients. when the internal jugular vein has not been successfully eannulated within minutes by the external landmark guided technique, the authors recommend the use of the ultrasound guidance. in the majority of cases right atrial or ventricular thrombi represent pulmonary emboli in transit. these may be fatal in patients (pts) treated conservatively with anticoagulation only. in literature the incidence of right heart thrombi in pts with proven pulmonary embolism (pe) is said to be in the range of - %. extremely mobile, long, worm-shaped masses in the right heart cavities carry an especially high early thrombus-related mortality rate which ranges from - %. current therapeutic strategies favour fibrinolytic therapy with consecutive anticoagulation. we report five cases ( male, i female, - years) of right heart and pulmonary thromboembolism. in these pts diagnosis and regression of thromboemboli following systemic intravenous lysis therapy with recombinant tissue-type plasminogen activator (rt-pa) was documented by transesophageal echocardiography (tee). a submassive pe occured in pts, a massive pe in pts. one patient (pt) had a cardiac arrest. in all cases tee clearly identified the extensive thrombns formation in the right-sided cavities of the heart and in the central pulmonary artery in cases. all pts were treated with mg rt-pa, pts in a front-loaded regimen over minutes, pt over minutes, and, due to the life threatening situation, in one case a bolus injection as ultima ratio was performed with no intracerebral bleeding complication. regression of thromboembolic masses after fibrinolytic therapy was demonstrated by transthoracic and transesophageal echocardingraphy after to hours. all pts survived and were put on coumadine, pt developed an intracerebral bleeding with persistent hemiplegia. conclusions: the use of thrombolytic therapy is highly efficacious for the therapy of pts with pe and concomitant right or ventricular thrombus formation. transthoracic and especially transesophageal echocardiography are powerful bed-side diagnostic tools for the immediate diagnosis and follow-up of successful treatment in this life-threatening condition. although widely used, catheterisation of the femoral vein in the groin using "landmark" technique is frequently complicated by accidental arterial puncture. suboptimal hygiene and patient discomfort are also associated with this technique. with regard to these last two factors cannulation of the femoral vein - cm below the inguinal ligament would seem an attractive alternative. as "landmark" technique is not possible for the cannulation of the femoral vein in this part of the thigh, ultrasound was used to locate the vessel and the results of this technique were evaluated. methods: a portable compact ultrasound device (site rite,dymax corp.) featuring a . mhz transducer (ultrasound depth - cm) fitted with a needle guide and a cm screen was used by residents with no previous experience in ultrasound guided cannulation. patients consisted of a surgical icu population. results: in patients catheters were introduced.in cases more than one ( - ) attempt was made and in patients the procedure was unsuccesfull due to the fact that the vessel was situated out of reach of the ultrasound (vessel depth > - cm), during the procedures one accidental arterial punction was registered. the catheters remained in situ for a mean of days (range - ) and were used for volume suppletion, medication, parenteral nutrition and haemodialysis.co-ionisation rates compared to those of subclavian catheters in our icu. in the first patients cases of asymptomatic thrombosis of the femoral vein were seer on ct-scans performed for other indications, in the following patients duplex scanning performed after removal of the catheter yielded another cases of asymptomatic femoral vein thrombosis. conclusions: ultrasound guided femoral vein catheterisation - cm below the inguinal ligament is a safe and simple technique that can easily be performed by residents without prior experience. the incidence and impact of thrombo-embolic complications associated with this technique are still subject to further investigation. objectives: to estimate the cost of antibiotherapy (ab-cost) in a multidisciplinary -bed greek icu and to correlate ab-cost with total cost of drugs and consumables and with patient's outcome, severity of illness and type of admission. methods: prospective data from consecutive patients admitted to the icu from / / to / / were studied. a tick chart was designed to record all drugs, materials and consumables regularly used for icu patients, but did not include low price drugs and consumables, which are provided from hospital's pharmacy as stock and were included in a fixed icu cost calculated for a month period. the chart also contained demographic details and data necessary for the calculation of several illness severity scoring systems. obiectives: over years evaluate the necessary efforts and expenses to implement a cis in the routine of a -bed stcu. methods: in june a commercially available, unix-based cis was installed on a -bed surgical icu. the goal was a paperless documentation at the bedside. after more than years clinical experience two aspects were investigated: what effort is necessary to install and support a cis, and what is the benefit for patients and personnel on the icu? results: the installation and support of a full-fledged cis requires a considerable effort: (a) the conceptual framework for the cis has to be defined. this includes the definition of documentation standards, as well as nursing and therapeutic standards, which is the essential basis for the configuration of any cis. (b) configuring a cis, i.e. "fine-tuning" it to the user's specific needs, is always a laborious task. moreover, constant maintenance is necessary. these tasks require the following personnel: experienced health care professionals for defining the conceptual framework, - trained health care professionals for configuration, system administrator. on a single icu ( - beds) these are not considered full-time jobs. (c) training is best done employing the "train-the-trainers" approach. (d) beside the necessary amount of man power and money to install and purchase a cis, administrative and mis support is needed, especially when interfaces to the hospital and laboratory information systems have to be set up. in general, a cis needs the commitment of all people involved. without a really professional approach with a longterm goal any major cis can turn into an unnecessary but inevitable night mare. after years clinical use and a thorough implementation of a cis on a major sicu it can be said that full-fledged cis offers an opportunity to dramatically improve the working environment on an icu. moreover, it adds to patient safety, quality of care and cost efficiency in one of the most advanced and expensive areas of medicine. conclusion: a major investment in man power and money is necessary to install and maintain a full-fledged cis. a sincere professional commitment to the goals of a cis is necessary. in exchange, a well configured and well maintained cis dramatically improves the quality of therapy and care on the icu. even return of investment and financial profitability of a cis seem feasible todayl from the clinical perspective it appears that the users themselves are the central determinant whether a cis makes a dream come tree or turns into a night mare. objectives: to establish a relationship between the activities of the staff and the occurrence of auditory alarms on the i. c.u. ard to evaluate confusion between auditory alarms. methods: laboratory based studies which investigated aspects of confusion between alarms in current use on the i. c. u. the observational studies were conducted over an month period and examined the frequency and duration of alarms together with the concurrent activites being undertaken by staff on the unit. the laboratory based studies showed that there were enduring confusions between the alarms on various items of medical equipment, for example a ventilator alarm and an e. c. g. monitor alarm. the results of the observation studies demonstrated that alarms are activated when specific activities are being undertaken by staff. sounds could be used in future recommendations for alarms on medical equipment. suggestions are also discussed for improving and rationalising auditory warnings in the i. c. u. obiectives: we investigated inferior petrosal sinus (ips), the lowest affluent to jugular bulb (jb), as a possible source of contamination of samples in jb for monitoring oxyhemogiobin saturation (sjbo ). pulling back the catheter the oxyhemoglobin saturation usually rises indicating extracerebral contamination (jakobs en met al: j cereb blood flow metab ; : ). methods: the study was carried out on patients undergoing ips sampling to differentiate cushing disease from ectopic acth syndrome and to lateralize any resulting pituitary lesion. we studied the value of oxyhemogiobkn saturation high in jb (sjbo ), at ips (sipso ) and at mid jugular vein ( th cervical vertebra) (smj ) bilaterally. results: we found significant differences between right sjbo and both right sipso (p= . ) and right smjo ( p= , ) and between left sjbo and both left sipso (p= . ) and left smjo (p= . ) we did not fred any difference bilaterally. objectives: we studied various methods of receiving and editing of clinical datas in critically ill patients (different ethiology). patients were investigated in regional intensive care center. methods : the following datas were studied : anamnesis, status praesens objectivus ( organs and systems ) ,. clinical and biochemical markers of critical condition , datas of eeg ,rheography . the medical information complex contained : channel electroencephalograph, -channel roencephalograph, ad-converter ( analog inputs, bit resolution, k hz), ibm dx , software includes set of routines for spectral eeg analysis, eeg-mapping, correlative analysis, and brain bloodstream reg-monitoring (written in turbo pascal . ), expert programs for estimation objective and humoral patient status (written in clipper . ) and statistics. there were used following programme-language instruments : borland c++ . , nantucket clipper . , ca-clipper tools ii. as the methods of statistical processing of dates were used: t-students criterion , fisher criterion, methods of correlation analisis, calculation of the regression levels, dispersion analysis, results : there was created the optimal structure of hard and sofware complex of search steady objective regularity in dynamic of critically ill patients condition. conclusion : the created system allowed to value effectiveness of intensive care and give us new opportunities in study pathogenesis of systems disorders in critical condition . over a five year period a patient data management system has been installed which allows individualised patient data to be accurately collected. using this data a costing system has been developed which ascribes costs thus: . direct costs -drugs, fluids, consumables, interventions. these are ascribed to individual patients, according to data collected from the pdms. . indirect costs -energy, depreciation, admm costs, maintenance etc. these are summed for the year and ascribed as an overhead per patient day. n.b staffcusts contain art element of both cost types the aim is to make as many costs as possibie 'direct', hence 'activity costs' have been calculated winch comprise staff time, drugs and consumables -these are direct costs. these costs of patient care are then searnlessly integrated into the financial and budget management of the icu environment. it was found that by calculating costs in this manner % of the total cost of icu are captured within the 'direct' element, and so are able to be ascribed to individual patients. this is much more accurate than simply dividing the total costs of ~cu by the number of patient days. temporal costs (variations during patient stay) and cross sectional costs (cost differences between admitting specialities) were also noted with interest. results of the initial analysis of data captured by the system will be presented. little is known about the resource costs (not simply cash costs) of icu. even less is known about individual patient costs, with previous estimates of these costs varying widely. however, if cost effectiveness studies are to be undertaken accurate calculation of individual, group and total icu cost is an essential, prerequisite, which, via this system of costing, is now achievable. information about intensive care of cancer patients is limited in the literature, despite the increasing use of such facilities in oncology over the two last decades. in order to determine if and how critical care facilities can be used specifically for these patients, we performed a world-wide inquiry in anticancer centers selecting the hospitals by using the international directory of cancer institutes and organizations. we mailed a questionnaire to centers and we received responses ( . %). there was at least one uncological (i.e. with > % of cancer patients) icu in (% % an -year old woman with graves disease presents with sore throat, vomiting, diarrhea, sinus tachycardia at /minute and a temperature of ~ several weeks before, treatment with propylthiouraeil had been stopped (rash and fever) and replaced by methimazole and ledide prior to a minor surgery. however, both drugs were discontinued by the patient two weeks before admission. shortly after arrival in hospital, patient's condition progressed to respiratory failure (upper airway edema), delirium and shock requiring icu admission, intubation and resuscitation with fluids and vasopressors. white blood count was /mm ~ with neutrophils. patient's hemodynamic data showed initial hyperdynamic profile followed by low output state with decreased sv ( %) (n - %) and cardiac index ( , ) (n , - ). echocardiogram confirmed cardiac chambers dilation as previously described in thyroid storm. lithium carbonate, corticosteroids, antibiotics and beta-blocker perfusion were given. plasmapheresis was started. free t& (n= , - pmo/l) went from , to , after the first two pheresis. after a remarkable clinical recovery, sub-total thyroideetomy was done i days after admission. in life-threatening thyroid storm, plasmapheresis is a very effective therapy when anti-thyroid drugs are counterindicated. purpose: to compare the reliability of prognostic indexes in crhically iu patients admitted in an intesive care unit (icu) who had acute renal failure (arfi and were treated with different dialytic techniques. material and methods: patients were included in a prospective study from june to november . patients presented arf defined by creatinin serum leve(s greater than pmol/l and previous normal levels. patients were divided in three groups. group i (control) : patients with arf who did not receive substitutive techniques. group ih patients under intermittent hemodialysis (hd) or peritoneal dialysis (pd). group ii : patients under continuous hemodiafiltrstion (hf). the statistical analysis was chi-square test and analysis of variance. results: the table shows the results we obtained, we did not find any significant difference betwen the two groups of patients undergoing dialysis. d(fferences were observed only between group i and the other groups as shown below. we did not find any significant association between the theoretical mortality predicted and the observed mortality according to saps in the three groups. due to exposure to a wide variety of unpleasant stimuli, for example, tracheal suctioning, venipuneture and physiotherapy, most pataents admitted to the icu will require some form of sedation. this review will describe the suggested properties of an ideal sedative agent for use in the icu and review the current limitations of some of the available agents from this perspactive. methods used to quantify the level of sedation, such as the ramsay score, glasgow coma score, newcastle sedation score and visual analogue scores, and their deficiencies will be examined. consideration will be given to defining the optimal level of sedation and the circumstances under which sedation might be varied over the icu course will be discussed. preliminary results from an ongoing study examining the role of light versus heavy sedation and ischaemia in a cardiac surgical icu population will be presented. the pharmacceconomics of icu sedation will be briefly addressed. finally, the role that sedation may play in increasing morbidity, pastieuiarly nosocomial pneumonia, in the icu will be discussed. objectives : therapy cost(tc) in icu patients is a substantial component of total hospital care cost. estimation of tc during this year, partitioning to various groups of drugs used and attempt to minimise it, were considered practically useful. methods : in collaboration with the hospital pharmacy we were able to have a complete report of au drugs used for icu patients (including enteral and parenteral nutrition). mean apache ii severity score upon admission was . and mean length of tcu stay was . days. price per drug unit and cost per group of drugs were also available drugs were divided into two groups: antibiotics ( ) cardiovascular drugs ( ), gastrointestinal system drugs ( ), enteral and parenteral nutrition ( ), respiratory system drugs ( ), sedative, analgesics and paralysing agents ( ), parenteral solutions with electrolytes, vitamins and trace elements ( ), anti-inflammatory agents ( ), protein substitutes and immunomodulation agents ( ), anticoagulative agents ( ). antibiotics were further subdivided into those "freely" prescribed (a) and those whose prescription and administration requires filling of a relevant form (b). results : !) tc for icu patients/day was . drs ($ ). total tc/patient was . drs ($ . . ). ii) partitioning total tc per group of drugs reveals : ( ) %, ( ) . %, ( ) . %, ( ) . %, ( ) . %, ( ) . %, ( ) . %, ( ) . %, ( ) . %, ( ) . %. t ) concerning antibiotics which consist the major cost component, group a and group b contributed by . % and . % to the total icu tc respectively. group b were administered to . % of all icu patients. conclusions : i) for the above studied patient population antibiotics consist almost half of total tc followed by protein substitutes and immunomodulation agents. ii) if tc control could be attempted in the icu, prescription of beth groups must be reviewed. appropriate treatment should be prescribed and readily provided to any patient. clinical significance of routine protein substitution, currently controversial, should be re-evaluated. new antibiotics (third & fourth generation cephalosporins, quinolones, carbaponems) should be prescribed on the basis of strict diagnostic procedures using modern technology available. rationalisetion of antibiotic therapy will lead to cost control, redistribution of icu expenses and substantial contribution to infection policy in our country. objectives: i -to investigate the clinic efficiency of the monitoring of the rso cerebral, in relationship to the stroke prevention, in patient undergoing carotid surgery. -to determinate the variations of the rso during the different surgical and anesthetic procedures in these patients methods: ten patients undergoing carotid endarterectomy. precise neurological exploration previously to the surgery and in the immediate postoperative period. angiography evaluation to the extend of carotid artery disease. invasive blood pressure, ecg, pulse-oximetry ( pso ) and rso were collected previousty to the induction of anesthesia. the premedication was administered intravenously -midazolam ( mcgr/kg) and fentanyl (i rncgr/kg) -. thiopental ( mg/kg),fentanyl ( mcgr/kg) and atracnrium ( , mg/kg) have been used for induction of anesthesia. co te is monitoring al~er the orotraqueal intubation ! the anesthetic maintenance is accomplished with lsofluorane ( , - , %) and bolus of atracurium and fentanyh the surgical procedure is standard (without arterial shunt during the carotid cross-clamping). we register each minutes: blood pressure, cardiac frequency, pso , co te and rso . the rso cerebral variate in relation with: the anesthetic induction, blood ~ressure, co te, cross-ulampping carotid and with the modifications of the head position. the maximum decrease of rso cerebral was in relation with the :ross-clampping carotid ( minimal value: ). no patient had neurologic complications and postoperative stroke after carotid endarterectomy were not observed. objectives: there are more than anesthesia in chelyabinsk emergency hospital every year. to % patients of it emergency anesthesia is applied. more than patients have ishemie heart disease (ihd), hypertansion (hp) and previos miocardial infarction (pmi). more than % of all patients are old patients (op). the resalts deep noninvasive bioimpedance monitoring (nbm) in surgical patients have been studied by us. methods: our nbm system "kentavr" includes parameters of cardiac and vessels function. it is realised by monitors in operation theatres and computer network. moreover we are able to examine surgery patients before anesthesia and perioperatively by using special computers system for cardiovascular reflex control by fast fourie transform (fft) of parameters simultaneously. results: pathients extremly needed peryoperative monitoring of hemodinamics. from these patients more % had stroke volume (sv) less than ml, n -co less than . /mim/m , % -ejection fraction (ef) less than n and % -puls bioimpedans microvessels (pbm) less than morn. patient had intensive care in special department. out of died. comparing with survived with these patients before operation hr was larger, sv, co,ef, pbm and puls bioimpedance aortha was smaller. much more of these patients were with ihd, pmi, hd, op. even with survived patients these parameters decreased the towards the end of operation. surgery patients had different variability of basic hemodinamical parameters with common tendency to increase power amplitude in low frequency by fft. conclusions: using of bioimpedanee noninvasive parameters allows to have criteria for corrections (infusies, vasodilatators, inotrops and others) and then us the final goal, to have more sucssesful surgery. with survived patients was perioperatively and postoperatively care more intensive. obiectives: the aim of the study was to compare the phi with the hemodynamically derived tissue oxygenation indexes as: oxygen delivery (do ), oxygen consumption (vo ), cardiac index (el), and arteriovenous difference in oxygen [(a-v)do ]. methods: patients ( males and females) with major trauma or major abdominal surgery were studied. on admission, a nasogastric tube allowing phi measurement was introduced and a pulmonary artery catheter was inserted for optimal hemodynamic management. each phi measurement was accompanied with a complete hemodynamic study comprising systemic and pulmonary artery pressures, blood gases, and cardiac output measurements with the thermodilution method. derived parameters vo , do , ci, (a-v)do were measured according to the standard formula. hemodynamic parameters were opt• as soon as possible with fluids, inotrepes, and vasopressors according to repetitive hemodynamic measurements. all patients were under mechanical ventilation. after hemodynamic stabilisation phi and hemodynamic measurements were repeated every eight hours, during a -hour study period. a total number of measurements were obtained and compared. statistics: results are presented as means + sd, correlations were performed between phi and the hemodynamically derived oxygenation parameters. a p< . value was considered as significant. results: mean values were phi= . + . , do = + , vo = + , c. = . + . , (a-v)do = . + . . no correlation was found between phi and do , phi and vo , phi and c.i, phi and (a-v)do . on the contrary in patients phi remained below . for more than hours despite adequate hemodynamically derived tissue oxygenation parameters. mortality in this group of patients was very high ( %). conclusion: no correlation was found between phi and the hemodynamically derived tissue oxygenation parameters our data suggest that phi is a better oxygenation indicator than the hemodynamically derived tissue oxygenation parameters, because it is closely related to the patient's outcome. objectives: the pathogenesis of septic shock and multiorgan failure is believed to be related to tissue hypoxia of the gastrointestinal tract. therefore new monitoring techniques, preferably organ specific, are required to establish the adequacy of tissue oxygenation. peep is used to reduce pulmonary shunt volume and improve blood oxygenation, but is accused to impair splanchnic perfusion. we studied mucosal oxygenation and perfusion on the capillary level in the stomach and the duodenum. methods: we used the erlangen microlightguide spectrophotometer (empho ll) together with a specifically designed fibre probe (bodenseewerk ger~tetechnik, berlingen) in combination with a standard gastroscope. measurements were performed on ventilated, traumatized patients (ages - years), with no evidence of shock or severe infection, after informed consent was obtained from the relatives. all patients were hemodynamically stable without inotropic support. an area of cm was analysed in the gastric corpus, the antrum and in the duodenum. in three patients we simultaneously measured the muc sal blood flow using a laser doppler flowmeter ( objectives: to investigate the influence of hb-o affinity in the monitoring of svo~ during improvement of cardiac index (ci) in cardiogenic shock. design: to state whether changes in svo: were associated in changes in actual pso (p~ ) and standard p~ (ps st) consecutive measurements of artero-venous bga, before an.d after therapy-induced changes in ci, were evaluated in patients (mean age -* y) suffering from cardiogenie shock, all under mechanical ventilation in psv modality. methods: together the hemodynamic measures, m~xed venous samples were analysed at ~ c using the abl radiometer for po , pco: and ph, and the osm radiometer for hbo %, hbco% and methb%. psost (i.e. the p~ at ph= . , pco:= mmhg and temperature at ~ c) was calculated automatically by the instruments on mixed venous blood as was the ps "in vivo" (i.e. the pso at the patient's value of ph, pco and temperature), using siggaard-andersen's computerizated algorithm. mean time between paired measurements was . -* . houm. the data were compared by anova test for linear regression and t-test for paired samples. results: a dose linear relationship was found between svo and oxygen extraction ratio (oer), r= . ,p= . . the improvement of ci ( . -* . to . + . l/min/m , p< . ) induced a significant increase in svo~ ( . -* . to . • . %, p<. ). a significant decrease in p ( . • . to . • . mmhg, p< . ) without any significant change in p~ st ( . • . to . • . mmhg, p=ns) was also found. these data show that either oer or the shift to the left of the oxygen dissociation curve account for increase in svo occurring with restoration of systemic blood flow. the program is intended to help the intensive care unit interne providing him with a practical tool when making decisions concerning patients in a critical condition. in his daily practice in intensive care unit, in this case the interne of the unit, uses this program for each patient as follows: on the first stage of data collection he should complete the following modules: ( )personal data ( )patient's pathology ( ) laboratory and~ monitor lug data ( )drugs prescribed or toxic elements ingested. in this way, the system allows optionally the consult with a computerized data base about the drugs prescribed, standardized parameters and techinques performed by the central laboratory. ( )reference to an antibiotics guide regarding becterian sensitivety in our unit, whitch ee checked every six month ( ) access to de questionnaired apache ii to load up new data. ( ) statistcs about patient's admission and discharge. results: once all data collection is finished the system performs the followin duties: ( )detailed drugs interactions, including toxic elements ( )diagnosis starting from the clinical, laboratory and monitoring data. in some cases, it also establishes therapeutic strategies, e.g. a coagulopathy ( ) give the l~narmacological incompatibilities between the drugs p~escribed and %he diagnosis established, and ( )perform dosage adjustments based upon the personal and pathological data. objeatve: to assess the power of diseri~,~ion ofa multiperpose severity score (sai~) when applied to subgroups ofpatieals (pta) according to their lemg~ of ~ay (los) in icu. design: in order to compute the saps probability, a model derived fi~m legible regression was developed. meaumree of calibration (goodmem..of.fit statistics) end discrimination (roc cm've and relative area under the cm've) were adopted in develotammtul asd validation set. the whole databue was ~ati~ed in five gronps reeked on los as follows: los = days, los = - days, los = - da~, los = - days, los > day~. area under the carve (auc) was ud~ninted for each ro~. s~ing: imlimlcus. patents: of ~ pts comec~ively admired ~ a period of three yeet~ ( ) ( ) ( ) , a total of was i~leded in this study. pts without saps, p~ yolmger them yearn, p~ with los shorter ~ hom'~ were excluded from this maly~is. iaterventinns: nose mema'onm~ end result: the logistic model developed gave good remits in terns of calibration md discrimin~on, both in developmental set (do.s g : . , p > . ; auc = . i- . ) and in validation ~t (g.o.g g : . , p > . ; auc = . ..+ . ). auc of each grottp showed a loss in di~zimination (i.e., prediaton) closely related with los, being . i- . in pts with los = days el . ~. ia tm with los > da~ (figure). following the present guidelines of integral management, in order to achieve optimization of sanitary resources and better use of facilities, we feel that the setting up of objetives is a key factor in the continuous process of improvement of quality care. postsurgical intensive care services maintain an interdepent relationship with other hospital services. within the general plan of the hospital it's of the utmost importance to delegate autonomy to the various depertments and service units in determining and achieving objetives. it's also necessary to establish mechanism for coordination of the activities in order to assure the succes of the program. the objetives cannot be improvised, they must be carried out in a specific manner in the following stages: .-analysis of the present situation (starting point). where are we?. defining objetives and making explicit the activities and methods to achieve them is to anticipate the future; it is of the utmost importance to comunicate said plans to all whom affect by encouraging them to attain the desired results. in the present paper we intend to show the guidelines to follow in carrying out a course of objetives. introduction:we presents results related to the quality of life (qol)of critical patients, from paeec project data. material and methods: the paeec project is a multicentre study define the type of patients cared for in spanish icus, and the therapeutic activity provided. ninety-five icus from spain are taking part. this study analyzes the qol of critical patients prior to their icu admission.for the evaluation of qol a questionnaire designed by our team for critical patients was used, with items grouped in sub-scales: physiological functions ( items); functional capacity ( items) and subjective aspects ( items). qol is classified in levels: normality ( points); slight deterioration ( - points);moderate deterioration ( - points); significant deterioration (>i points). the we present results related to therapeutic activity in critical patients and their age, from the paeec project. material and methods: the paeec project is a multicentre study to define the type of patients in spanish icus, and the therapeutic activity provided. ninetyfive icus from spain are participating. this study analyzes therapeutic activity in the first hours as evaluated by tiss, and related factors. results: the sample was , patients, sge . ~ . years. severity by apache ii system was . • points. the tiss score was . • points, distributed as follows: i (<i points): %; ii (i - points): %; iii ( - points): %; iv (> points): %.there is a positive correlation between the level of therapeutic activity and severity by apache ii (r = . , p < . ), and a very weak but negative correlation between tiss and age (r = - . , p < . ), so that an increase in age corresponds to a lower level of therapeutic activity.patients the multivariate analysis of the relationship between tiss and age took into account: severity, existence of previous history, need for mechanical ventilation, size of hospital, diagnosis and mortality. it indicated that there continued to be a relationship between therapeutic activity and age, so that as age increased, therapeutic activity diminished. conclusions: therapeutic activity performed on critical patients is less in the oldest patients, in whom excessively aggressive procedures are limited. a relational data base management system in the icu. c. kotsavassiloglou*, d.matamis, g. dadoudis, j. kioumis, d. riggos. icu dep., g. papanicolaou gen. hosp., exohl, thessaloniki, and * a' neurological clinic of aristotelian university, thessaloniki, greece. objectives: the introduction of the information technology in the i. c. u seems to be unavoidable because of the large amount of produced data and the need for their systematic analysis. such an information system should be a) easy to use, b) friendly to the user, c) powerful and d) modular. on that basis, we created a patient data management system (pdms) according to the expectations of the medical staff of an eighteen bed multidisciplinary icu. methods: we selected paradox for windows v . for the implementation of a relational data base because this program meets the above mentioned criteria. informations regarding the patients include a) demographic data, b) previous medical history, c)diseases upon admission, d)complications during hospitalization and e) outcome data. the diseases' registration consists of items classified in categories upon the principal system affected. specific informations about the need and duration of mechanical ventilation, nutrition, renal replacement, right heart catheterization and icp monitoring are also available. an extension was added concerning icu infections and related informations about antibiotic-resistant pathogens. all icu pathogens can be matched to their resistance or sensitivity and cost of antibiotics. the program can perform queries and various statistical analyses based on complex criteria. new modules can be added later according to the future needs and remarks of the users. results: the program was well accepted by the medical staff and patients were registered as a test. the first analysis of the data related a) observed mortality versus the apache ii predicted mortality, b) mortality according to the age, gender, pathology aud duration of icu stay and c) pathology upon admission and icu related complications. conclusions: the long term use of this pdms can be an efficacious research tool. it can be used in retrospective or prospective studies by addition of necessary modules. the first data analysis revealed the iack of an international diseases' classification system. the development of a worldwide common classification system is essential for the compatibility of the data analysis among various icus. this will allow the realization of multicenter trials on a large scale. s. nanas= n. sphiris, a. precates, a. lymberis, m. pirounaki, and ch. roussos dept. of critical care, university of athens, athens, greece the complexity of the cases submitted to an icu, the variety of underline disease, tbe severity, as well as the large number of substances administered to each patient constitute obvious the need of support with an easy available dss. this system will assure the safety of the administered treatment will help to adjust the dose according to the situation of each patient and it will screen for possible interaction and incompatibilities between the administered drugs. the goal of the present effort is the design and development of a software system acting as a decision support tool to physicians of icu. the application is organised around a relation database management system (rdbms) that consist of: a) all available substances ( . ), b) all generic names of medications available in our country for each substance, c) incompatibilities ( . cases) and d) interactions with other substances ( . cases). the following figure shows the structure of the rdbms. y ta~ortato~ [ c~rs using the stored parameters for each patient the dose and the rate of administration of selected substances will be possible to calculate. the continuous monitoring of the treatment for each patient supports the medical staff to make the necessary changes of the prescriptions. the application is currently developing in wireless pen based computer systems which place patients at the centre of "islands of information" located throughout icu. in conclusion this dss is a powerful and useful tool for icu staff because it provides without additionai work to the routine of daily practice, the currently available information for each order concerning drug interaction and incompatibilities as well as treatment monitoring is to obsea~ among critically ill pfdieats, stdjdivided following the diagn~s at the adn~ssio~ the diffmeax:es in the ~ and oxyplx~efic l~mmems bawe~ strvwors [s] and non sumvors ins] and to test the pc~'bih'ty to have soar survival criteria, as earliest as tx~able. method~ :we made a ~ study on consexa~e ~ilically ill paliffas, subdivided in series following the diastases at the admission: medical pafiea~ ( s and ns), surgical patients ( s and ns), a~d poliwauntas ( s and ns). follow up was done at d,.ays from the admission in ice. all the patienls were ramitored with a ~ c~eter and laeno:lymmi. "c and o .x.xyphorefic txuamaers va:~e couected at fin~es (t): at fiae ~draission (t ), at x~ars from t (t ), at (f ), (y ), (t ), % (t ) and horus from t cf ). in~,h ~ies, for ~y ~ a all the lin'~ n~an and sandaid d~viation was ~ tx~h for s and for ns. th~ betw~ s and ns tl~ roeaas of ~h porarneter ~e ccmpared tt~ng t-lest and p < . w~ considered ska~ significant in each series in the t wheae the mast significative diffemx:as ~goeamd bet~en s and ns, we made a txedictive criterion, asamting as predictive indices for stnvival the i:r values, higher or lower than flae treans of the ~rar~ers of au flae patients, axx)rdhlg to those ones t~iatistically diff~'e~ betw~m s and ns. fhmlly xse co:weatxt onaong the series the nrametees of the st~rs with the analysis of variance, to daserve the lxjsable differealt irea~ of sty hflices, following the diagn~s of admission: :nedkal, angical patient or poll~tam results: we c~ld not find ~ predictive criterion for politraonaas, perhaps ixx:ause of the few ntanber of l~fients. for high ri~ saw~cal patieras the following criterion at t has a sensitivi .ly of ~ ,and a ~ecificity of . %: sv > . nffmin/n~, map> mmhg, pmap< nmalqg cvp<i nunhg will nmah& lvswi> g m/m , sxo > ~ do > mlhnin/m , o er< %. for lx~dical l~tienls at t the following criteric~a has a ser~tivi.ty of % and a ~zificity of . ~ cvp< . mn~g, sao > %, s,g) > ~ vo i< ml/nfin/m , o er< %, shunt< % survlvops' data of the series ~ signitic~atly differenl~ both for the t~mody~nic a~ for fl~e ox rphomfic lxlmn~s; moreover we ~ that the vatt~ of hemodynamic mad ox.~ho~tic indices were higher in politrautms. conclus'ions: acx~ording to the fftffe~mt patho!o~es, the ~ rnelabo~c needs are diffeten~ so that it is juslified to mash ~ the~alceutic goals, following the type oflmthology. hen~ we foru~d for high ~k mrgical pmka~ and for medical patier~s assme, ff mllslied, a good prognosis while, if n [ ntljsfled~ the plinsliclioil ofdl~tth is no[ g(ioct finally, ab~ high iis~ supgical palieaats, according to what other atmhors say, txatws sh ~'n~ers ' therapeutic goalsvvould seem inadeqt~te, bec~jse they need a gear physiologic and themtx~ic elth~ in rdation to the rretabolic needs. figure ) . thus, the smaller european nations had a greater participation than ~e larger ones, with the exception of norway. a similar result was evidenced for contributions to intensive care medicine (figure ). these findings can be explained by different submission policies and language banners. however, there was no significant correlation with the gross national product of each country. conclusion: we conclude that the smaller european countries generally contribute more to international intensive care journals than the larger ones. objectives: to evaluate the agreement between a new and three old methods measuring ctp and to assess their reproducibility. methods: we studied patients ventilated with a siemens c respirator. we measured ctp by dividing the tidal volume with the increase in airway pressure (paw), either with the respirator setting used (ca) or with a fixed setting (cf). by modifing the inspiratory time (ti) without changing inspiratory flow, we were able to deliver two series of inflations ( , ,... ml) before and after curarisation of the patient. the same volumes were also inflated in paralysed patients with a super syringe. at the end of each inflation a plateau of sec was performed and paw was recorded. the above three sets of pressure-volume (pv) points were used to reconstruct the corresponding pv-curves (( , c , c the new method for ctp measurement without a super-syringe had the best reproducibility in paralysed patients and gave similar results without curarisation in the majority of them. however, agreement between the methods tested was unacceptable for clinical purposes. further investigation is required in order to improve the accuracy of ctp measurement in icu patients. m kunert, r.sorgenicht, l.scheuble, k.emmerich, h.g ker med.clinic b (dept.of cardiology) i heart center of wuppertal/university witten-herdecke,germany objective to determine the accuracy of activated partial thromboplastin time (apl-l) and activated clotting time (act) studies when samples are drawn through heparinized central venous catheters (cvc). methods a total sample of paired act/p't-/" values was analysed in patients ( m., f., + y.) for monitoring heparin therapy.all patients had a cvc (certofix trio,braun,frg) in the internal jugular vein receiving a continous infusion of . u heparin via the central catheter.act (hr-act, hemotec,usa) and ap'i-f (neothromtin, behring,frg) samples were drawn from the cvc using the double syringe technique (removing and discarding ml blood before drawing the sample). these blood samples were compared to act/ap'cf blood samples obtained by venipuncture (v.fem.) at the same time, act values were analysed directly in the intensive care unit (icu),api-i samples were measured in the hospital laboratory within minutes. results ac-i -~ pi-f~ cact/~pi r = , ) cvc samples + + . v.femoralis samples " + + p-value n.s. n.s. conclusion there is no difference in heparin anticoagulation studies drawn from heparinized central venous catheters compared to those obtained by femoral venipuncture,withdrawing ml blood prior to obtaining the blood specimen is a safe way for eliminating heparin contamination.not only the aptt test but also the act test is a useful method for heparin anticoagulation assessment in the icu. objectives: evaluation of the delicate balance between filter-coagulation and patient-hemorrhage using heparin as anticoagulant in continuous renal replacement procedures. methods: from january through august , we studied filter surviva[ and hemorrhagic complications during filter periods in critically d[ patients, treated with continuous arterio-venous hemo(dia)filtration, with special emphasis on the heparin dose, concurrent use of coumarins, systemic activated partial thromboplastin tirne(aptr), platelet count, mean arterial bloodpressure and the type of filter used. results: filters ( %) were disconnected because of coagulation. mean survival of multiflow an filters was twofold shorter compared to survival of fh gambm filters. a total of hemorrhagic complications occurred of which three patients died at aptt values of respectively , and seconds. after adjustment for mean arterial bloodpressure, platelet count and the type of the filter, the risk for filter-coagulation decreased % (relative risk . , %c . - . ) for each ten seconds increase in aptt. the risk for patient-hemorrhage increased % (relative risk . , %ci . - . ) at an aptt-increase of ten seconds. the occurrence of filter-coagulation and patienthemorrhage was not correlated with the administered dose of heparin. concurrent use of cournarines had a positive effect on filter-survival, without increasing the overall incidence rate of patient-hemorrhage. conclusions: the systemic apt]" is a good predictor of the risk for filtercoagulation and patient-hemorrhage. heparine therapy seems optimal at an aptt between and seconds, although one should realize that fatal hemorrhagic complications still can occur. objectives: the alterations in vascular tone which are primarily regulated by adreno-sympathetic tone(ast) are compensatory responses in hemorrhagic patients. this study was designed to evaluate the correlation between vascular tone and ast in patients with hemorrhage, methods: the vascular tone was expressed by volume elastic modulus (ev) that is defined as; ev = ap/(av/v) (ap; the arterial pulse pressure, av/v; the volume change ratio). ev was measured using a non-invasive transmittance infrared photoelectric plethysmography (tipp) and a volume oscillometric sphygmomanometer . we prospectively studied patients with hemorrhage. the initial ev measurement was performed on arrival and repeated for a hours duration. as a parameters of ast, serum concentrations of adrenalin (ad), noradrenalin (nor), plasma renin activity(pra) were measured simultaneously. we analyzed the correlation of ev and conventional parameters to ast by multivariate statistical analysis. results: ev values at transmural pressure mmhg on admission and hours later were respectively . + . mmhg, . +_ . mmhg (mean + sd). systolic pressure(pas) and serum hormones on arrival and hours later were respectively, pas; . _+ . , + . mmhg, ad; . _+ . , . _+ . ng/ml, nor; . _+ . , . + . ng/ml, pra; . _+ . , . _+ . ng/ml/hr. the ev values correlated significantly with ad (r= . , p= . , n= ), nor (r= . , p= . , n= ), pra (r= . , p= . , n= ). by multivariate statistical analysis, ev correlated more significantly with ad and nor and pra (p= . ) than the conventional parameters such as pas, heart rate and pulse pressure. conclusions: the alterations of ev correlates closely with ast. the compensatory mechanism in hemorrhagic patients can be detected noninvasively by ev monitoring. obiectives and method: autologous oxygenator blood was processed at the end of cardiopulmonary bypass (cpb) by either hemofiltration (hf , , m , fresenius) or by cell washing with a onntinous autologous transfusion system (cats, fresenius). prospectively the blood of patients for each group was processed and then retransfused intravenously to the patient. besides, volume and time requirements, standard hematologic chemistry, coagulation and complement activation were measured. results (mean values for oxygenator blood at the end of cpb, and results of concentrate after processing by filtration or washing): both processing techniques show excellent hemoconcentration of the diluted cpb blood with a good transfusion effect for the patient. filtration retains all plasma proteins and large molecular weight plasma bound waste products. in contrast, cell washing with cats significantly depletes plasma proteins and waste products. the newely developped cats machine gives eonsisinnt laboratory result in a fully automatic continuous processing mode. in conclusion, both filtration and washing are effective for processing cpb blood. filtra tion yields a highly concentrated whole blood, whereas cats washing produces a high quality autologous erythrocyte concentrate. soluble fibrin has during the last years gained interest as a marker for the activation of the coagulation in connection with various clinical conditions, e.g. disseminated intravascular coagulation, deep venous thrombosis and myocardial infarction. elevated levels of soluble fibrin in plasma can be detected by the chromogenic assay coaset fibrin monomer, relying on the ability of fibrin to enhance the tpa-catalyzed conversion of plasminogen to ,plasmin. using this test, it has been shown that the level of soluble fibrin can be correlated to severeness of illness in critically ill intensive care unit patients. a revision of the coaset fibrin monomer kit has now been made and the new product, coatest soluble fibrin, is considerably more convenient to handle and gives higher resolution at low fibrin levels. the test is performed by the addition of a buffer dilution of the plasma sample to a microstrip well containing the colyophilized mixture of tpa, plasminogen and the plasmin specific cbromogenic substrate s- . the reaction is allowed to proceed at,. room temperature for minutes before discontinuation. the absorbance at nm, measured in a microplate reader, is proportional to the content of soluble fibrin in the sample. the assay is carefully standardized and calibration curves are provided in the kit. the convenient and rapid assay procedure makes the coatest soluble fibrin test well suited for single test analysis in acute situations. objectives : blood coagulation abnormalities have been reported in the systemic blood of patients with cerebral lesions. the physiopathology of such events is not yet completely understood. we compare the coagulation profile of blood from the right jugular bulb with systemic blood of patients with head injury. methods: we studied patients, who were admitted to our neurosurgical intensive care unit between january and march with head injury and no other associated pathology (age - yrs), a glasgow coma score <= g, no abnormality in baseline coagulation profile and no history of coagulopaties. the patients did not undergo angiography. a one-way gauge certofix catheter was inserted through the right internal jugular vein up to the jugular bulb. an identical catheter was inserted through a subclavian vein. blood was sampled from either catheter (a=atrial; j=jugular) - hours after trauma (t ) and t hours later (t the inddence dpontolx'rative thmmhi~e and haumord~gic complieatiom were assessed in padents treated with indobefen, heparin calcine caeca), low mollecolar weight heparin (lmwh) (f.nosheparin) and undergoing hemodiludun, blood predeposhing, intra mad postoperative blood saving. ]'he indolmfon tempota~.norks platelet aggregation through ,,elective inhibition of the cyclatygenasis and thus atacbldonicadd( ).tbe n'mimum effect occurs after hours from the fast administration and is still present after hours. ~- patients, mean age --- yrs., weight --- kg were studied. ( . %) were male and ( . %) female. onderwent hip prosthesis ( previously plate and screw removal) hip revim'un ( stem, cop and stem + cop), tutal knee prosthesis, in the st anaesthesidogy depl from - to - - . as for antithromboembolic ptephylam, apart from hemodihitiun pts were with treated indobufen ndo), with heparin ealdum caeca) and with low mo!lecular weight hepam (lwr, ). as the slightest clinical and/or imtmmental suspidon of deep vein thrombosis (dv'i') or polmonary umbolism(pe), a phlebogram or sdndgram were respectively carried out. -the inddence of homologom transhisiom was significandy lower (p= . l) in the padeats treated with indobufen ( . ) compared .'ith heca ( . %). the con~gency table shows statistical signifleance for the use of heca in patients with vein deficiency in the lower limbs, past dvr and/or pe, coronary heart disease (cdh'), while there is no correlation for renal, cardiac or liver defidency, obesity, systemic hypertemion, atrhythmy, diabetes, chronic bronchitis and rheumatoid arthritis. by comparing the postoperative cumplications with the risk factors, there ks a highly significant correlation (p= . l) between cdh and thrombotic and humord~agic complieatiom (pe, death, he~atoma, die use of hum_ologous blood). thee data show that hep~in, preferred in patients with c'dh, roost likely for leagal-tuedical reasons, did not have the de~'ed effect. conclusions -the stastisfical aar~ais shows ~nifieanfly different efflea~ (pro . ) between the therapies (see table) : it can be seen that in patients undergoing autotramfusiun and hemedihidon, indobufen produo~ a lower incidence of haemotrhagic complieatiens compared to heca and lmwh and is more effective in the prevention d ~c complications at clinical e~idence. the duration of i~toperadve hospital stay is signi~cantlylonger for patients transfused with homologous red ceils and treated with hec, .a ( . -+ . days) and lmwh ( . +- a days) compared with indo(ll. _+ a days). one of the main causes for postoperative complications in major orthopaedic surgery is postopemtive bleeding with local effects in the operation site (hematomata, pain and delayed mobilization) and/or systemic and subsequent cardiodrculamry repercussions that are sometimes severe. the aim of this study is to assess the possibility to apply a new system of monitoring, control and saving postopemtive blood loss from the drainage. the bt recovery dideco (marandola, modena-italy) ~ used since it is the only apparatus capable of doing this. the apparatus consists of a pressure transducer, adjustable from - a + mmhg, which activates a peristaltic pump connected m drainage robes. the bt recovery display shows hourly bleeding in the first hours, total bleeding, time passed since the start of monito~g and subsequent salvage and the aspimtioo pressure on the drainage robes; the latter is inserted at - mmhg and then modified according to bleeding/minute, g bt recovery also has an alarm that sounds automatically if.' blood loss is more than ml/hour; air is in the circuit; the batteries are running low. materials and methods: pts were studied ( m and ~), aged . -+ .lyears, basal hemoglobin . -+ (range . - . )g/all, treated from st january, to mst december, in the st service of anesthesia and intensive care unit of our hospital. the patients underwent the following surgical treatment: total hip revision ( pts), cup revision (~ipts), stem revision ( pts), total knee revision ( pts). the average dumtion of the operations was -+ min. intranpemtive monitoring and blood salvage was applied to all patients. genera! anesthesia was used on pts. and integrated (epidural analgesia + light general) on the remaining t . anttthromboembolic prophylaxis consisted of external pressure bandage, isovolemic hemodilution with iodobufen in ( . %)pts., calalc heparin in ( . %)pts., low molecular weight heparin in ( . %)pts.; pt did not give a predepoalt of blood, gave unit, pts units, pts units, pts units. the data obtained was statistically analysed using contingency tables and anova. results: average intmop salvage was -+ ml, average postop salvage was -+ mi the average intra+postop +- ml. average postop loss was -+ ml. the global incidence of postop complications was: h~natomata . %, dvt . %, pulmonary thromboembolism , , myocardiac ischemia . %, acute myocardic infarction . %, respiratory deflciecy . %, arrhythmia %, cystitis . % there were nn complications in . % of pts. postop bleeding over ml in under minutes (with bleeding alarm activation) occurred in pts ( . %). this sta~tically correlates only with the type of operation performed (more frequently in total hip revision p= . ) and with a significant decrease (p~ . ) in the pruthrombic activity detected about hours after the operation. this bleeding, also made the alarm sound, calling the attention of staff who could act accordingly, by making the drainage pressure positive and incre~sthg the tension of the external pressure bandage. conclusions postop monitoring, control and blood loss salvage combined with predepoalting and intmop salvage has enabled allogenic transfusions in % of cases to be avoided in operations with high postop blood loss like hip or knee revision. the usefulness of the system can be seen by the fact that in the patients with so much bleeding to set off the alarm, there was no significant difference in the incidence of allotransfusions and complications. references )borghi b., bassi a., de simone n., laguardia am., fonnaro g. an injury of the brain may result in various disorders of hemostasis caused by the release of • into the circulation through a damaged blood-brain bar tier. disseminated intravascular coagulation(dic) is one of these disorders. it is a freguent but relatively rare ly diagnosed complication of subaraohnoidal haemorrhage. the aim of this study was to evaluate some parameters of both blood coagulation and fibrynolisis in patients with sah.in addition one wanted to find out wh~ther potential changes correlated with the pa• condition in the acute phase of sah and whether they influenced the course of this disease. patients with sah were studied. in of them sah was due to closed eraniocerebral injury and in the rema ining resulted from vascular malformation. the following parameters were evaluated:the prothrombine time,the activated partial thromboplastin time, the thrombine time,level of factor v,fibrinogen degrada tion products and fibrin monomers. the results let us show the presence of oic in patients with closed craniocerebral injury and in with vas. cular malformation despite the lack of clinical symptoms the tests in posttraumatic patients and in patients from second group showed incomplete dic.on admission patients with such changes in measured parameters were in poor condition.the course of the disease and the effe cts of treatment were also worse in these patients. the results showed ihal in patients with sah complex disorders of both coagulation and fibrynolisis occur, and they depend on clinical condition of the patient. they also influence the course of the disease. methods : charts of all patients admitted with d.i.c. over a ten year period ( - ) were reviewed. diagnosis of dic was based on the association of fibrinogen < g/ -platelets < / -fpd > ~tg/ml in the hours of the admission. results : patients -mean age + y -saps +_ -gestanional age _+ weeks -the two first conditions associated with d.i.c. were placental abruption ( %) and preeclampsia or eclampsia ( , %). bleeding episode was present in pts ( %) and surgical treatment has always been necessary. pts ( %) were given packed red ceils ( + u) and fresh frozen plasma ( + u). patients were given platelets packs. heparin was never administered. pts required mechanical ventilation and two patients hemodialysis. all the patients survived. correction of prothrombin time (p.t.) and fibrinogen (f) was quick (p.t. at t h ~ % -f at t h , + , g/i). but platelets count remained low (plat. at t h + / ) -no difference was observed in patients who received platelets. conclusion : prognosis of critically ill o.p. is good. blood loss is the main complication. correction of hypovolemia and anemia with concomitant surgical treatment are essential. the administration of coagulation factors or platelets is still under discussion. objectives: to evaluate the effects of antithrombin iii i at-iii) and a protease inhibitor, gabexate mesilate foy), on the coagulation and fibrinolysis in disseminated intravascular coagulation (dic). methods: after the approval of our institution and consent from patient's family, patients with a dic score ( , japan) more than points (dic or having a risk for dic) entered this study. they were randomly divided into two groups, foy (i- mg/kg/h for days or more) treated group and no foy group, each of patients. platelet count (plt), fibrinogen (fen), at-iii fibrin degradation product (fdp), d-dimer (do), fibrin monomer (fm), thrombin-antithrombin complex (tat), plasmin-plasmin inhibitor complex (pic), and prothrombin time ratio (ptr) were measured before the start of treatment (at admission) and i, , and days after the admission. at-iii at units for days was administered if the at-iii at admission was less than %. finally the patients were divided into four groups: group a, foy (+) and the at-iii ~ %; group b, foy (+) and the at-iii < %" group c, foy (-) and the at-iii %; group d, foy (~) anffthe at-iii < %, each of patients, to match the patients for backsrounds. all parameters, dic score and survival rate in a month following treatment were compared among the four groups. results: the at-iii and plt from day to were significantly higher in groups a and c than in groups b and d. the fdp, dd, tat, and pic after treatment decreased significantly from the baselines in groups a and c but not in groups b and d. the fgn and fm were not significantly different among the four groups. the ptr decreased in groups c and d but increased in group b. the dic score decreased significantly in groups a and c than in groups b and d. survival rates were %, %, % and % in groups a, b, c and d, respectively, although not significantly different. conclusions: in patients with dic or a risk for dic, foy had no expected effects but at-iii had suppressive effects on the coagulation and fibrinolysis mechanisms. a prognostic factor ? carbon monoxyde intoxication is a classical complication of inhalation injury. carbon monoxyda is also physiologically produced during the heme metabolism: heme is conversed to bi]irubin by the hemeoxygenase which is an intracellular stress protein. icu patients (pts) were studied prospectively for apache ii score and carboxyhemnglobin (hbco) arterial level to assess if hbco level could be correlated with the severity of the pts. objective: to evaluate a new technique of non-surgical tracheotomy. patients: adults, mean age years and children, mean age months ( me.- yrs). method: through a needle inserted in the trachea, a guide wire is retmgradely pushed out of the mouth and attached to a special device formed by a flexible plastic cone with pointed metal tip joined to an armoured tracheal cannula. this device is then pulled back through the oral cavity, larynx and trachea, and outwards across the neck wall by applying traction on the wire with one hand and counterpressure on the neck wall with the fingers of the operator's other hand. when the cone and / of the eannula have emerged, the cannula is cut off from the cone, straightened perpendicular to the skin, rotated and advanced caudally to its final position. results: endoscopic control facilitates and improves the safety of all manoeuvres. the pointed cone easily pierces the tissues, and the cannula is extracted without difficulty since it has the same outer diameter as the cone. tissue adherence around the cannula is absolute thus preventing local inflammation. the time in apnea required for dilation and cannula placement does not exceed see., and it is well tolerated because within safety limits in patients hyperventilated with oxygen. only one case of bleeding occured in a patient on dialysis with severe coagulopathy. autoptic findings in subjects who died due to progression of primary disease showed a very regular stoma with an almost complete lack of hematic and flogistie infiltration in recent tracheotomies. .conclusions: translaryngeal tracheotomy (tlt), by virtue of its greater inherent safety and lower tissue trauma than percutaneous techniques, can also be carded out in infants and children, a severe test bench for any tracbeotomy technique. further specific indications are recently stemotomized patients, since tlt is associated with a low rate of infection, and short term tracheotomies after laryngeal surgery, to prevent obstructive complications. references: fantoni a., translaryngeal tracheotomy, apice, ed. gullo, trieste, , . background: inhalation of no has been shown to reverse hypoxic pulmonary vasoconstriction , to reduce pulmonary pressure in pulmonary hypertension of different origin and to improve gas exchange. in putmoflary embolism, pulmonary hypertension is caused by mechanical vascutar obstruction and by reactive vasoconstriction. the effects of inhaled no in putmonary embofism has been partiatly studied' the purpose of this study was to investigate and determine the effects of no inhalation on pulmonary hemodinamica and gas exchange in a hypoxic canine model of pulmonary embolism. methods: two groups of adult mongrel dogs were studied: group (control} dogs and group (no inhaled) dogs. both groups were anestesized with tiopental, mechanically normoventilated with an hypoxjc mixture of and n~ (f[q , ) and instrumented (swang-ganz catheter, femoral artery catheter) pulmonary embolism (pe) was induced by fisher's method s. no inhalation ( ppm) in group was started rain. pdor to pe and kept constant throughout the experiment. no inhaled concentration was analyzecf by chemiluminiscence technique. pulmonary artery pressure (pap), central venous pressure and sistemic arterial pressure were continuosly recorded. cardiac output, artedat po~ (pan ) and mixed venous po~ were measured in both groups under hypo)dr conditions, before pe and , , and rain. after pe. pulmonary vascular resistance (pvr) and gas exchange (pao fio:~ ratio), were calculate using standard formulas. data were process and analyzed with non pararnetdc test, and reported as mean -so and statistical significance was considered if p < , . : no produced an increase in arterial oxigenation (pao /fio~ ratio) and reduced pap before pe induction in group . after pe we found no significant difference with .respect to the time eour.se of pap, pvr and gas exchange between beth groups throughout the experiment. probably, the severe mechanical obstruction produced in pulmonary embolism masked the small effects of no inhaled. obiectives: blood volume measurement would be useful in critically ill patient management if it were easy to perform. this is not the ease and current methods are based on radiolabelled red cell dilution. inhalation and uptake of a known mass of carbon monoxide (co) gas and measurement of earboxyhaemoglobin increase can give results accurate enough for clinical use. this requires a rebreathing system providing oxygenation and carbon dioxide removal, yet complete retention of all carbon monoxide administer&l, and so most authors hand ventilate with a bag and waters soda-lime canister, adding oxygen as necessary. we aim to popularise this method by; i)design of an automatic co administration system driven by the itu ventilator and ii)writing of software for a portable computer to perform all necessary calculations method: we show the computer is use estimating the co dose required and later estimating the blood volume. we also show the new gas administration system. this is a fully closed circle attached to a "bag in bottle", driven by the ventilator. the novel feature is the mechanism by winch driving gas (set to % ) spills automatically into the circle, balancing o uptake by the patient, yet allowing no co loss. conclusions: this equipment is easy to use, reduces human error and allows optimum ventilator settings to remain. the operator merely administers the volume of co determined by the computer and takes blood on two occasions. carboxyhaemoglobin measurement is easy to perform, thus there is a cost saving also. with our modifications use of this technique may potentially become more widespread, the video demonstrates the method in use in our itu. - ( %) underwent conventional surgical therapeutics. " ( %) with resection of tracheal stenosis with end-to-end anastomosis(rts). i ( %) with broncoscopic dilatation. one patient died and the others still have stable patency(sp) without continued treatment. - ( , %) have received endoscopic laser ablation with or without calibration tubes. of them ( , %) are receiving continued endotracheal treatment until now. ( , %) have sp wihout continued treatment. -i ( , %) endoscopic laser therapeutic case turned to rts and is having sp. conclusion: conventional surgical aproach has been progressively replaced in our hospital by endoscopic laser ablation and silicone calibration tubes. this study suggests that these technics are effective and could be the elective treatment for iatrogenic stenosis. obiectives: hemorrhagic disorders due to thrombocytopenia and thrombocyiopathia remain one of the most serious complications during long-term extracorporeal membrane oxygenation (ecmo) in patients with severe acute respiratory distress ~drome (ards). in the presented study, nitric oxide (no), kwown as a potent endogenous platelet antiadhesive, disaggregating and antiaggregating compound, was evaluated for its possible antagonistic effect on platelet trapping when added to the gas compartment of membrane oxygenators (mo). meti~ods: two parallel separated extracorporeal circuits, consisting of heparin bonded hollow fiber oxygenators (minimax, medtronic, carmeda eioactive surface), tubing systems, low pressure reservoirs, and roller pumps were prepared. for each measurement, a pair of circuits was simultaneously filled blood from the same volunteer. low-heparinized fresh warm blood was obtained from four healthy volunteers, who had no drugs for at least two weeks. the gas inlets of both oxygenators received dry gas ( % oxxygen, % carbon dioxide, % nitrogen); gaseous no ( ppm) was added to the gas of one of the oxygenators (no-mo), whereas the other one (mo) was used as control. after minutes no gas was switched off, so that the no-mo received no more no, and no was added to the gas inlet of the membrane, which had no no before_ to assure iutracircnit volume stability, drawn blood for measurements was replaced with saline, and platelet counts were corrected for dilution by hemoglobin values. the mean of four platelet counts (coulter counter) of each timepoint (start, , , , , , , , and minutes) was used for statistical analysis (paired sample t-test). results: in the no-mo platelets remained at + , % (percentage of baseline value, mean -+ sd) until min. in contrast, platelets of the mo continuously decreased after start and were significantly lower after minutes ( , + , % vs _+ , %(p< . ); min. , -+ , %vs , _+ , %(p< . ); min. , _+ , % ( p < . ). after switching of no gas to the mo, further decrease of plateleta was stopped and platelets remained at , +_ , % until termination of circulation. platelets of the former no-mo decreased slightly after cessation of no gas to , _+ , %. conclusions: these data indicate that gaseous no significantly attenuates platelet trapping in hollow fiber oxygenators, when added to the gas compartment. this might be a new therapeutical approach for membrane oxygenator induced thrombocytopenia during long-term ecmd. objectives: nitric oxide (no) plays a pivotal role in regulation of vascular hemostasis. several studies elucidated the antiadhesive, antiaggregating, and disaggregating properties of endothelially synthesized no to platelets. additionally, agonist-induced no production in platelets by the l-arginine-no pathway was found as a negative feedback mechanism after platelet activation. although noplatelet interactions were intensively studied by several investigators, no data exist, about changes in platelet surface molecule expression in no-modulated platelets measured by flow cytometry using monoclonal antibodies (moabs). methods: p-selectin (alpha-granule-membrane protein, gmp- , cd p) and glycoproteiu (gp , lysosomal protein, cd ) are expressed only after platelet activation and degranulation. activation was quantified in thrombin ( . u/ml) and adp ( . ram) stimulated platelet rich plasma samples (prp). blood was obtained from healthy volunteers (n= ), who had no drugs for at least days. for evahiation of no-modulated activation, the spontaneously noreleasing compound sin-i ( . mm) ( -morpholino-syndonimin-hydrochlorid) was added in parallel prepared samples prior to the addition of agonist. platelet surface molecule expression was evaluated with moabs directed against cd a (gpilbliia, fibrinogen-receptor, phycoerythrin(pe)-conjugated), cd p (fitcconjugated), and cd (fitc). only cd a-positive signals were gated in sideangled light scatter, and assayed for activation marker expression (defined as percent of gated population). results: basal p-selectin expression was . + . %, and increased to . _+ . % after thrembin-activation, and to . + . % in adp-stimulated samples. addition of sin- attenuated p-selectin expression to . - - % in thrombin (p<. , two-tailed paired t-test), and . + . % (p<. ) in adpactivated platelets. basal gp expression was . _+ . % and increased to . + . % in thrombin, and to . _+ . % in adp-stimulated samples. with sin-l, gp expression decreased to _+ . % (p<. ) in thrombin, and . : . (p . ) in adp-stimulated samples. conclusions: these data implicate, that no leads to a significantly reduced activation of surface molecule expression in thrombin and adp-stimulated platelets. in addition, flow cytometry might be a useful tool for studying modulation of platelet activation by no or no-releasing compounds. introduction: acute cadmium poisoning is very rare. on initial presentation may mimic metal-fume fever, but acute inhalation cadmium toxicity may produce fatal chemical pneumonitis. case report: we present a case of acute fatal respiratory failure secondary to cadmium-fume irthalation. a year old patient was trasferred from another hospital with acute respiratory failure presumably due to pneumonia. the last days before he had had commom cold symptoms. he had been cutting with a welder during one hour without any respiratory protective measure. three hours after exposure he developed progressive dispnea and was admitted to hospital. with presumtive diagnosis of respiratory infection, antibiotics were begun, however be failed to improve. all microbiological studies were negative. chest x-ray showed bilateral diffuse infiltrates. on seventh day he needed intubation and mechanical ventilation and on th he was admitted to our icu. antibiotics were stopped and new microbiological studies were performed including brochoalveolar lavage and virologic studies. all results were negative. he developed progressive hipoxemia and hipercapmia and finally, multiorganic disfunction syndrome. he died days after exposure. the metal he had been working with was a % cadmium alleation. blood cadmilam concentration days after exposure was . mcg cd/g cr, and urine cadmium concentration was . mcg/l. on postmortem examination, tissue cadmium concentrations were: blood ng/ml, liver ng/g, kidney ng/g and lung ng/g. these values confirm that cadmium was the cause of the fatal respiratory illness in this patient. conclusion: this case evidences the considerable hazard of acute poisoning after inhalation of eadmium-fume and stresses the need of appropiated safety measures against metal-fume poisoning. aim : lactic acidosis is considered the hallmark of cyanide poisonirig. however, the relationship between plasma lactate and blood cyanide levels has not been determined. the aim of this study was to determine the significance of plasma lactate concentration (plc) during the course of cyanide poisonings. methods : the patients were included according to the clinical suspicion of pure cyanide poisoning at the time of presentation. fire victims were excluded. serial blood samples were collected before and after intravenous hydroxocobalamin (hoco). blood cyanide concentration (bcc) was measured colorimetrically. plc was measured enzymatically. results : patients were studied. on admission, plc ranged from . to mmol/l, and bcc from . to gmol/l. mean systolic blood pressure was • mm hg, mean arterial ph . • . , mean anion gap was . + . mmol/l and mean pao . • . kpa. three patients died. before antidotal treatment, there was a significant correlation between plc and arterial ph (p = . ), anion gap (p = . ) and bcc (p = . ) but not with heart rate, pao , paco and blood glucose, or blood pressure. during the whole course of the poisoning, a plc _> retool/ was a sensitive and specific indicator of a blood cyanide concentration > ~tmol/ . sustained catecholamine administration reduces the correlation coefficient. conclusion : baseline measurement of plc allows assessment of severity of acute cyanide poisoning. thereafter, plc may be used to assess the adequacy of antidotal treatment, more especially in patients not requiring sustained infusion of catecholamines. aim: the aim of this case report was [o study the correlation between the plasma lactate levels and several clinical, biological, and toxicological parameters serially measured during the course of a cyanide poisoning treated with a high dose of hydroxocobalamin. a -year-old male ingested potassium cyanide leading to cardiac arrest. cpr was performed prior to hospital arrival where the patient received g hydroxocobalamin. sbp rapidly returned to normal allowing withdrawal of epinephrine. the patient remained comatose and died from brain injury days after the ingestion. methods plasma lactate and blood cyanide levels were measured serially. blood cyanide levels were measured using a colorimetric method.~ plasma lactate levels were measured using an enzymatic method. for correlation spearman rank correlation test was used. results. initial plasma lactate and blood cyanide levels were mmol/l and gmol/l, respectively. there was no overall correlation between sbp and either blood cyanide or plasma lactate levels. similarly, there was no overall correlation between arterialvenous oxygen saturation difference with either blood cyanide or plasma lactate levels. in contrast there was a strong correlation between blood cyanide and plasma lactate levels (r= . , p< . ). the time-course of the blood cyanide concentrations was described by a mono-exponentiai decay (r = . ) with a blood half-life of . h. similarly, the time-course of plasma lactate levels was described by a mono-exponential decay (r = . ) with a blood half-life of . h. discussion. in this case of acute human poisoning, sbp was a much poorer indicator of continuing cyanide effect both before and after antidotal treatment, than was lactate production. this suggests a potential clinical role for following serial plasma lactate levels as a marker of the evolution of cyanide toxicity. aim : cyanide (cn) poisoning in fire victims is frequent and rapidly fatal. in a prospective study we tried to assess the clinical tolerance of a high dose of hydroxocobalamin (hoco) administered at the scene of the fire in fire victims suspected of cn poisoning. methods : inclusion criteria : soot in mouth or sputum ~ any degree of neurological impairment. exclusion criteria : children, pregnant women, burns of total surface body area > %, multiple trauma. protocol desigrl following examination and the collection of a blood sample in dry heparin, a g dose of hoco ( g in case of cardiovascular collapse) was administered intravenously over min. the systolic blood pressure was monitored before and after the administration of hoco, and one hour later. results : there were females and males. the mean blood cn concentration was • pmol/ . the mean blood carbon monoxide was . • . mmol/ . nineteen fire victims eventually died. among the non-cn-intoxicated patients (blood cn < ~mol/ ), there was no significant change in arterial blood pressure. in the cn-intoxicated patients (blood cn > gmol/ ) a significant increase in blood pressure was observed both immediately (p < . ) and hour later (p < . ) after the admistration of hoco. no allergic reactions were observed. conclusions : in fire victims with cyanide poisoning, the administration of a high dose of hydroxocobalamin was associated with an improvement in systolic blood pressure. hydroxocobalamin is well tolerated in fire victims without cn poisoning. objectives: tricyclic antidepressant (tca) overdose can lead to serious complications including cardiac arrhythmias [ ] . because of the known risk of early deterioration and the implication for management, emergent evaluation is essential. we determined the diagnostic usefulness of the electrocardiogram (ecg) in tca poisoning. methods: retrospective study of all patients with tca intoxication (pos. ,toxicology screening in urine and/or pos. history) in a -beduniversity hospital from through . the severity was graded with mild= no symptoms or agitation; medium= disorientation, somnolence, tachycardia, or convulsions; and sever~ coma, significant arrhythmias or death. we analysed the first ecg after admission with a special emphasis on qrs-and qtc-intervals and the terminal ms frontal plane qrs-vector (tqrs), which, was reported to lie typically between + and * + + • the best correlation with severity grade was found with qrs-and qtc-duration (p= . ), the tca-dose (p= . ) and hf (p= . ); tqrs did not correlate. patients died ( . %). conclusion: qrs-and qtc-prolongation in the admission ecg, and the reported dose of ingested drugs are useful predictors for severity of poisoning due to tricyclic antidepressants. we did not find additional benefit in determining the terminal ms frontal plane qrs-vector. objectives: since treatment of amphetamine poisoning is usually symptomatic and often associated with a fatal outcome, a search for specific drugs to help the amphetamine-intoxicated victim is sorely needed. methods: we report a case of a suicidal ingestion of large amounts of the amphetamine-derivative , -methylenedioxy-ethamphetamine (mdea) and heroin (diacetylmorphine) and present the hypothesis that the two drugs produce opposing clinical effects. results: a year old caucasian male was admitted to the emergency ward because of acute-onset confusion. at presentation, he was agitated and showed increased muscular rigidity. he had taken tablets of "eve" (mdea, approx. g) and g of "smack" (heroin) by oral route approximately h before admission. because of rapidly progressive tachypnea and exhaustion, the patient was intubated and ventilated. the serum concentration of "eve" on admission was ng/ml (lethal range - ng/ml). trace amounts of cocaine and substantial amounts of heroin ( ngtml; mean value in heroin-related deaths: ng/ml) were also found in the serum. the patient was successfully weaned from the ventilator by day and recovered without persistent neurobehavioral disturbance. despite high serum levels of both drugs, the patient did not present with the classic signs and symptoms normally seen during intoxication with these drugs. amphetamines in general, and mdea in particular, have opposite clinical effects to heroin or diacetylmorphine. none of these were however present in the case presented despite the high ingested doses and the serum levels in the lethal range. conclusions: the fascinating fact that, apart from the respiratory depression, none of the clinical signs reported after massive overdose with these two drugs were present, might be attributed to the opposite pharmacological effects of mdea and heroin. we believe that the patient unwittingly saved his own life by the oral coingestion of both mdea and heroin. our clinical data raise an interesting point about the pharmacological treatment of acute poisoning with amphetaminederivatives. introduction: the acute attack of aip still carries a significant risk of mortality of around %. a succesful outcome depends on early diagnosis, removal of pricipitating factors and provision of intensive supportive therapy. objectives: twenty one patients ( females, male) with documented aip were seen over a -year period in the university hospital. patient was in clinical remission and were with the acute attack of aip, among them with respiratory paralysis were required artificial lung ventilation and -assistant ventilation with peee pathologic treatment during the attack was normosany, adenil, androgenes, glueosa, riboxin parenteral and enteral nutrition via nasogastric tube. symtomatic treatment -pethidine, propranoton, antibiotics, bronchoscopia. methods: intermittent phasmapheresis was performed on patients. the following measurements were peformed: level of porphobilinogen (pbg) in the wire and delta-aminolevulinic acid in the blood. hematological and routine chemical evaluations, hepatic, hemodynamic and respiratory function. results: after plasmapheresis the median pbg excretion (normal range - mkg per/ kgr creatinine) fill from mkg on admission . mkg, then on - day raise to mkg and then during treatment with normosong and prasmapheresis lowest level was . mgk. fatalities occured in two females during attacks with proforma cerebral involvement and patients attained clinical remission. conclusion: after therapy with plasmapheresis normosong we found that there was consistently reduce the urinary excretion of pbg and shortening the duration of the acute attack. objectives: pigs has been reported to present with a higher pulmonary arterial pressure (ppa) and stronger pulmonary vascular reactivity than many other species, including man. aim of the present study was to compare pulmonary vascular impedance (pvz) before and after embolisation in weight-matched adult dogs and minipigs. methods: we investigated pvz spectra in anaesthetized and ventilated (fio . ) minipigs and dogs. after baseline measurements the animals were embolised with autologous blood clots to reach a ppa above mmhg. results: flow ( and ppa matched pvz data (mean-+sem) are shown in the table. [zo = hz impedance (z; {dyn.sec_em- }); zl = first harmonic z; zc = characteristic z; z phase = first harmonic phase a@e {radians}; fmin = frequency of pvz the first m{n~mam; *, f p at least < . between dog and minipig, and before v~. after embolisation respectively]. before case report: a -yr-o]d woman affected by legs recurrent thmmbophlebitis, was admired in medmine department for tach.~pnea, chest pain, tachycardia and cyanosis. before starting two-dimensional transesophageal echocardiography (tee) to confirm the suspicion of pulmonary embolism, she suddenly had ventricular fibrillation. resuscitation and defibrillation were readily performed. when sinus rhythm was reinstituted she was in superficial coma with preserved corneal and light reflexes: right hemiplegia, poor perfusion and h~posphygrma of the left arm. tee showed dilation of rigth ventricle (rv), incomplete occlusion of pulmonary arter~ (pal at it~ hifurcation, severe tigth-to-left shunt through a patent foramen ovate, paradoxical embolism with incomplete occlusion of left subclavian artery mechanically ventilated with vt= ml, rr= /mm, fio =l, the patient had ph= . , pao = mmhg and paco = . systemic bp was / mmhg and hr= b/min with low dose epinephrine ( . g/kg/min) a thrombolytic infusion (rtpa: mg/ h) through a peripheral vein was started tee imaging and clinical status hours later were unmodified. a new rtpa infusion was performed through the pulmonary hole of a swan-ganz catheter with the tip close to the embolus. one hour later pa pressure decreased from / mmhg to / mmhg, etco increased from to mmhg and sao improved from % to % three days later the parietal, spontaneously breathing and with normalized tee scans of rv and pa, was transferred to rehabilitation service to perform physical therapy. conclusions: massive pulmonary embolism in a patient with patent foremen ovale, paradoxical embolism and refractory hypoxaemia was unaffected by systemic rtpa infusion, while intrapulmonary rtpa administration dramatically improved gas-exchange, hemodinamics and the general conditions of the patient. the presence of a large rigth-to-left _atrial shunt and the rapid rtpa metabolism could likely explain the effectiveness of its intrapulmonary administration in front of failure of systemic thrombolysis. introduction. cardiogenic shock during massive pulmonary embolism (blpe) is due to an acute increase of right ventricle (rv) afterload and possibly rv ischemia causing a failure of rv pump function. the rec~;mmended therapeutic strategies are: xoiume augmentation ~n ~rder m }ncrease rv pre-h~ad, adrenergic drugs to increase t'ontractillly and maybe coronary perfusion, fibrinolytic drugs to delermine clot lysis. there have been several reports of noradrenaline (na) as a useful drug in this setting for its sluing ~z, but also ~, properties. case report.an obese },ears old woman was transferred to our icu for tetanus. she was given the usual antibiotic and immunoglobuline therapy. l'wo thoracic epidural catheters were put in place at different levels and replenished with marcaine qid. a continous infusion of sedation (diazepam § was started together with mechanical ventilation. curarization ~,as given occasionally. fraxiparine . /die was used for prophylaxis of thrombotic disease, on day th at . a.m. she started to be hypoxic (sa %), tach ,tardic l l(i b/rain.), her blood pressure(rp) dropped frum norma~ values to r mm/hg, the central venous pressure (cvp) raised [rom lb to mm/hg and the end tidal co was mm/hg lower than one hour before. the physical examination of the chest revealed a clear bilateral ventilation and the chest x-ray was normal apart from an elevation of the :tiaphragm as compared to the previous. an e.c.g. showed sinus tachycardia, right bundle branch block and a possible inferior necrosis (which was already present on admission). a trans-thoracic echozardiography was performed which showed "an acute overload of the right centricle wilh remarkable dilatation. tricuspidal regurgitation ++. paradoxical movement of septum. small left ventricle with normal wall kinetics". the cardiac enzymes were later shown to be normal. an acute massive pulmonary embolization was assumed m be present.. a bolus of streptokinase x i(i u. was given fonowed by a continous infusion . two liters of colloids were also given in a sh~rt time, two hours later the patient was still deeply hypotensive, hypoxemic and anurir(bp / mm/hg, cvs mm/hg, spo %) despite a cominnus infusion of dobutamine fag/kg/min and adrenaline . ~tg/kg/min. at this stage a bolus of aoradrenaline ,g was given followed by a cnntinous infusion of . !*g/kg/min. an immediate improvement of the hemodynamics was noticed and one hour later the bp was / mmhg, the cvp mm/hg, the sao % and a brisk diuresis started. the hemodynamics kept stable and weaning from vasoactive drugs was achieved within two days. one month iater the patient was discharged home in good conditions.. con c i u sio n.ne administration may help to restore rv coronary flow and ;~ump function during mpe. aeute putmonary t~omboembo~sm [ffe) cou be mamfeslated with either respiratory or cardiovascular syndromes or both. the arm of the study was to establish leading respn'atory symptoms, frequency and form of the roendganographic (rig) changes as well as blood gas disturbance degree in acute pte with dommam respiratory disease appearance. the study includes retrospeotive analysis of i pte patients (pts), males (average age , yrs) and .q females (average age , yrs). they were admitted at university, olinie" with suspection ofpleuropnlmonary disease, including pte. final diagnosis of pte was based o~ evident risk factors in , % of the eases (deep venous thrombosis, surgery, trauma, imobilisation, malignancy ere), acceptable clinical, rtg, sdntigraphic and laboratory findings, as well as deep veins examination by dopple~-sonographie and radioisotopic -~enogmphy. respiratory symptoms appeared in all cases: sudden pleural pain ( %), dyspnea ( %), hemoptysis ( %), cough ( %) with association of two or more symptoms in %. chest xrays findings were abnormal in % with diaphragmal elevation ( , ~ lung opaeilies ( , %), atelectasis ( , %), plemal effusion ( , %), main pulmonary brancah asimetry ( , ~ oligemia ( %), heart shadow changes ( , %) and pulmonary arteries "cut off' ( , %). the association of two or more abnormalities was found in , % while normal chest x-rot was found in ~ of the cases. hypoxemia with pao < , kpa was found in , % followed with hypocapnia and respiratory alealosis in , % in , % of the gas exchage analysis were within normal limits. among cardiovascular symptoms short syn~cpa appeared in i , %, ecg changes-st q t type in "~ , %. results show high frequency of positive ~g findings in pte pts that is opposite to oppinion that chest x-ray in acute fie is the most ofran normal. leading symptoms are pleural pain and dyspnea, while hemoptysis were found in a half of the study group. blood gas changes were present in two thirds of the cases. kakkar, in his classic work ,clearly demonstrated the efficiency of low doses of heparin in prevention of deep vein thrombosis (lancet : , ) .after this first study the application of heparin prophylaxis became more and more diffused until to be considered a routine in many surgical departement.actually application of blood saving technique induces postoperative hemodilution effect. in that condition prophylaxis routinely applied seems a nonsense and can be at risk for postoperative hemorrhage. methods: to analize this problem we compared patients arrived in our intensive care unit (i.c.u.) in. : (group a) with arrived in : (group b) .every patient was operated for major abdominal surgery.in each one we considered the hemoglobin (hb) value,hematocrit(hct), and coagulation pattern (c.p.) at the arrive in i.c.u. and hours later. the patients was also divided in those receiving heparin prophylaxis (i) from not treated patients (ii) results:the application of blood saving technique clearly appears from the hb and hct level wich have a mean value of , +/- , (hb) and +/- (hct) in group a while in group b mean value are , -/- , (hb) and +/- (hct).patients of group a (ii) are the only one where a pathologycal c.p. with statistical significance has been demonstrated.in this goup we got four cases of evidence of venous thrombosis and one of pulmonary embolism.in patients of group b(i) we encontered the incidence of two cases of severe hemorrhage despite the absence of statistical significance in c.p.modifications. oxygen desaturation during broncho-alveolar lavage: role of oxygen saturation monitoring in prevention of acute respiratory insufficiency g. galluccio, b. valeri, s.batzella, m. di lazzaro*, servizio di endoscopia toracica, ospedale forlanini, rome, italy * servizio die anestesia a rianimazione, osp. forlanini the broncho-alveolar iavage is a diagnostic procedure employed in interstitial diseases of the lung. it requests the introduction through the working channel of a fiberoptic bronchoscope, after occlusion of a segmentary bronchus, of aliquots of saline solution at c, subsequently gently reaspired, in order to remove cells and proteins from elf (endoalveolar lining fluid), which is related to interstitial medium. bronchoalveolar lavage induces deep effects on pulmonary function: -lowering of the alveolar surface of exchange; -shunt effect, depending on the perfusion of non-ventilated districts; -increased pulmonary arterial pressure, due to hypoxic vasoconstriction; -decrease of lung compliance. in this report the authors present the result of oxygen saturation monitoring in a group of patients with interstitial lung disease, who underwent diagnostic broncho-alveolar lavage. in most patients with severe interstitial involvement, the lavage performed without supplement of oxygen induced a severe fall in the oxygen saturation during the late phase of the procedure. if supplementary oxygen was delivered during bronchoscopy, since its beginning, only slight modifications of the curve were detected. in patients without thickening of interstitium, in whom the lavage was performed in order to obtain material for bacterial or cytologic examination, no modification of oxygen saturation was observed in standard procedure. as conclusion the authors strongly reccomend monitoring oxygen saturation in patients with radiologic evidence of interstitial involvement also in patients with no evidence of dyspnoea. g. galluccio, b.valeri, s.batzella, m. di lazzaro*, servizio di endoscopia toracica, ospedale forlanini, rome, italy * servizio die anestesia a rianimazione, osp. forlanini the treatment of choice in patients with alveolar proteinosis consists of pulmonary lavage. this procedure requests the introduction, through the working channel of a fiberoptic bronchoscope, segment by segment, of aliquots of saline solution at c, subsequently gently reaspired, in order to remove the proteins deposited in the alveolar spaces. the method is very similar to that used in bronchoalveolar iavage, a diagnostic procedure used to obtain cells and substances from elf (endoalveolar lining fluid), which is related to interstitial medium. as known, bronchoalveolar lavage induces oxygen desaturation, because of shunt effect. understandably, one lung lavage has remarkably more deep effects on pulmonary function than bronchoalveolar lavage, for the amount of fluid introduced, the length of the procedure and the conditions of controlaterai lung. in this report the authors present the result of oxygen saturation monitoring in a patient who underwent pulmonary lavage for alveolar proteinosis. in the lavage performed without supplement of oxygen a severe fall in the oxygen saturation was observed during the late phase of the procedure. if supplementary oxygen was delivered during bronchoscopy, since its beginning, only slight modifications of the curve were detected. as conclusion the authors strongly reccomend the subministration of supplementary oxygen in pulmonary lavages, also in patients with excellent respiratory conditions. a. b. dublisky prof., m. r. isaakjan ass., v. a. zasukha, s. m. vinichuk prof., v. p. tserty ass. prof., chair of anaesthesiology, resuccitation and medicine of catastrophes, neurology of ukrainian state medical university, kiev, ukraine. objectives: detection of plasmophoresis's influence of results in treatment of ishemic insult. methods: we ve investigate patients with ishemic insult, treated with reverse plasmopheresis in complex treatment. after primary infusive therapy we took ml of patients' blood and separated it within min with rotation frequensy of /rain. after separation of erythrocytes from plasma, the latter has been returned to patients. we made - procedures during - days. hemoglobin, hematokrit, time of blood coagulation were determinated. the brain blood flow in internal carotid arteries, regional volum brain blood flow and total brain biood flow were evaluated with tetrapotar chest rheography and tetrapolar rheoencephalography. obtained date were comparised with control group after traditional treatment. results: it was found that after reverse plasmopheresis the hemoglobin and hematokrit levels decreased significantly in studied patients' plasma (from + . g/l to _+ . g/ and from + . % to _+ . % respectively). the time of blood coagulation by lee-white has increased by - . times (up to - rain). the level of brain blood flow has been increased significantly after reverse plasmopheresis in comparison with control group. the following tests of brain blood flow have been increased: a) the total volume brain blood flow from . + . ml/min to . _+ . ml/min (p < . ); b) the regional brain blood flow from . _+ . ml/min to . + . ml/min (p < . ); c) the brain blood flow in internal carotid arteries from . _+ . ml/min to . + . ml/min (p < . ). conclusions: the use of reverse plasmopheresis in complex treatment of patients with ishemic insult aiiows to improve rheological blood patterns, helps to increase volume brain blood flow. it results in quicer reparation of neurological functions. objectives: a prospective evaluation of the efficacy of continuous infusion of verapamil in reducing the incidence of postoperative atrial fibrillation after pulmonary surgery. methods: a total of consecutive patients, on verapamil, on placebo was included after lobectomy or pneumouectomy. a loading bolus of verapamil ( mg over minutes) was followed by a rapid loading infusion ( . mg/min) for minutes and finally a maintenance infusion ( . rag/rain) for hours. results: a mean plasma level of verapamil of ng/ml was obtained only after more than hours. atrial fibrillation occurred in five out of patients who tolerated the verapamil infusion, and in out of patients on placebo (p = . ). verapamil infusion was not tolerated in patients because of hypotension or a heart rate of less than /min, within hours of the start of the therapy. when atrial fibrillation occurred, the ventricular response, mean _+ sd, was not significantly slower during verapamil infusion ( + ) compared to placebo ( + ). conclusions: because of its frequent side effects and the only modest efficacy verapamil should not be considered for prophylactic therapy of atrial fibrillation after pulmonary surgery, and is probably not a good first choice for slowing the heart rate in case of rapid ventricular response once atrial fibrillation has occurred in these patients. results: study of haemostasis in these patients has showed deep disturbances of blood coagulation. fibrogen level has reduced to . + . g/l, fibrinogen and/or fibrine degradation products concentration have enhanced to . _+ . g/l, monofibrin soluble complex concentration to . -+ . g/l, blood plasmin level was enhanced to . + . mmol/ , plasminogen proactivator level was also enhanced to . + . ram, plateletes aggregation has decreased to %. after plasmopheresis aggregation was decreased in . times. it has been connected with decrease of fibrin and/or fibrinogen degradation products level and level plasmin in . times, and plasminogtnt activator level in . times. at the same time we have observed increase in total antifibrinalitic activity of blood in . times. activity of activators plasmine and plasminogene proactivators has decreased in . times and in the same time activity of activation inhibitors and antiplasmines has increased in times. conclusions: plasmapheresis leads to considerable improvement of a general condition and reduction of the haemorrhagic syndrom's sings (controlling of gastrointestinal haemorrage, reduction of intensity of subcutaneons haematoma). evaluation of continuous cardiac output (cc ) monitoring based on thermodilution technique in critically ill patients. methods: cardiac output (co) was monitored continuously using a modified pulmonary artery (pa) catheter, on which a heating filament is located and by which energy is transmitted to the circulating blood. a microprocessor calculated co by a new algorithm. standard bolus thermodilution technique ( ml of ice-cold saline solution) was used to compare cc with intermittent bolus cardiac output (ic ) measurements. the following subgroups were prospectively studied: i. heart rate (hr) > beats/min, . cardiac output > i/min . cardiac output < . i/min, . rectal temperature > . ~ and . pa catheter was inserted for more than days. results: a total of pairs of ic and cc measurements were obtained from the patients. bias (ico measurement minus cc measurement) of all measurements were . • i/min and the % confidence limits (mean difference• were - . / . i/min. also in the subgroups, cc measurement agreed closely with ico measurement (c > i/min: bias= . • i/min; co < . i/min: bias=- . • i/mln). elevated temperature and prolonged lay-days of the pa catheter did influence agreement of cc measurement with ic measurement neither (> ~ bias= . • i/min). conclusions: monitoring of cc using a modified pulmonary artery catheter with a heated filament has proven to be accurate and precise also in the critically ill when compared with "standard" intermittent bolus thermodilution technique. this method enhances our armamentarium for more intensive monitoring of these patients under various circumstances. background: the number of patients who need coronary artery surgery was) grows every year. most of these surgical operations are with extrar eircuiation (ecc). since january , this surgery is made without ecc in selected patients in our hospital. this technique is exceptional in spain. this type of surgery has proved useful in patients requiring revascularization of the left anterior descending, eireunflex or right coronary artery (not for grafting the pos~tefio~r descending branch}. blethods and results: since , patients aged to years (mean years) underwent cas without ecc. the mortality in programmed surgery was %. no patient was reexplored for hemorrhage. the mean values of some clinics parameters v~ere: a) blood requeriments: units per patient, b) need of mechanical ~entilation: i , hours, c) postoperative bleeding: cc, d) days at icui , . we used the student % t test or fisber~s exact test to compare these results with the mean values of surgery with ecc: a) blood requeriments per patient (p< , ), b) need of mechanical ventilation: hours (p< , ), c) postoperative bleeding: cc (p< , ), d) days at icu: (p< , ), e) programmed surgery mortality: % (p< , ). conclusion: our limited experience shows that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated pathology and in jehova's witness. the need of mechanical ventilation, days at icu, blood requeriments and morbi-mortality were fewer than surgery with ecc. to study the hemodynamic and antiarrhythmic influence of ace-inhibitor enalapril in acute myocardial infarction (mi). methods: holter ecg monitoring, heart rate variability analysis, echocardiography ( and l days after beginning of the treatment), stress-echocardiography and stress ecg ( - -th day after the onset of mi). enalapril was included into the treatment of pts with mi (study group), with normal or increased blood pressure, from the -st day of the disease. the data were compared with pts treated without enalapril (control group). results: silent ischemia during stress-test was registered in pts of the study group and of control group, the arrhythmia episodes during stress test -in and pts and episodes of silent nocturnal isehemia -in and pts correspondingly. enalapril importantly attenuated the hypertensi~re re~aetioh % stress test. in pts of the study group the number of perifocal hypokinesis zones decreased; in the control group it didn't change. the quantity of ventricular extrasystoles in the patients of the study group decreased by %; the heart rate variability indices improved as well; in the control group the character of ventrieulir arrhythmias, heart rate and its va]~i~bili%y didn't change significantly. conclusions: the inclusion of enalapril into the treatment of mi is a useful t ol to improve hemodynamie parameters and decrease the incidence of ventricular arrhythmias. objectives: to study left ventricular (lv) systolic function in the patients with acute myocardial infarction (ami) before and after peroral captopril test. methods: the original echocardiographic parameter of lv contractility, "coefficient of effective systolic function" (cesf), was proposed in the study. cesf is calculated from lv stroke volume (sv), obtained from doppler aortic flow in lv outflow tract and lv end-diastolic diameter (edd): cesf =sv/edd. the study included patients with ami, who had local lv dyskinesia and global lv systolic dysfunction (ef< %). besides cesf, the ejection fraction was calculated before and after administration of mg eaptopril (on the fifth day of ami) by methods of bullet and simpson. results: the dynamics of these parameters, as well as heart rate (hr) and mean blood pressure (bp), is shown in the tabte. before cal~topril ef (bullet) . • . ef (simpson) . introduction: the cold system is a monitoring system for measurement of right (copa) and left (coart) ventricular cardiac output, cardiac function index (cfi), fight ventricular ejection fraction crvef), fight ventricular cnddiastolic volume (rvedv), intrathoracic blood volume (!tbv), global enddiastolic volume (gedv), lung water (etv) and excretory liver function (pdr). patients and methods: pts have been monitored by the cold system. above mentioned parameters are measured by thermal dye dilution and a fiheroptic femoral artery catheter. copa, rvef and rvedv measurements additionally were compared to measurements by the baxter explorer. :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: ;;;k;;;;i cov (%) explorer ! ! [ gedv, itbv and pdr showed a significant decrease dufing the first - h after the operation, cfi and rvef si~canfly improved after k wheras etv showed a i~ in the early postoperative phase and fell to normal ranges at h. comparison of cold/explorer m~ements sb wed good correlations. discussion: concerning m ~toring of ri,ght ventric~ar function cold and explorer can he seen as equal. rvef gives an ar report about the performance of the right ventricle without use o f echocardiography. measuring itbv and gedv ~ improve ~gement and con~ol of th.e volume status, monitoring etv helps preventing lung edema. pdr shows good corre|ati n to liver blood chemistry and is bedside avai|ab|e. thus the cold system offers additional parameters for comprehensive m~nitofing of pts. ~e~ ~c surgery. obiectives: to evaluate the influence of an a!'~ered cardiac function on the cardiovascular response to the increase in oxygen demand induced by an increase in core temperature. methods: this preliminary study included adult critica!ly ill patients monitored by arterial and pulmonary artery catheters in whom thermodilution cardiac index {ci) and arteria! and mixed-vef)ous blood gases measurements could be obtained before and after an acute change in core temperature of at least . ~ (max rain apartl the patients were separated in two groups according to their cardiac function: patients had an impaired cardiac function as defined by a history of cardiac disease and an ejection fraction below % and patients had normal cardiac function. results: individual data are shown in the figure. in contrast to the control group (continuous line) in which c! increased without changes in oxygen extraction ( er), the q er in patients with impaired cardiac function (dottled line) increased without changes in ci. conclusions: the increase in oxygen demand associated with changes in temperature is met by an increase in c! in patients with unaltered cardiac function and in an increase in o er in patients with altered cardiac function. temperature should be taken into account in the assessment of the adequacy of cardiac output in patients with impaired cardiac function. objectives: to define the hemedynamic and metabolic response to physical therapy(pt) in relation to the type/level of sedation and the cardiac status in icu patients. methods: we studied mechanically ventilated icu patients ( • years) in stable hemodynamic status (no change in vasoactive treatment for at least hours), separated in groups: group = deep sedation, cardiac dysfunction required dobutamine (n= )r group = deep sedation (barbiturates), unaltered cardiac function (h=lo), group = moderate sedation, altered cardiac function (h= ) and group = moderate sedation, unaltered cardiac function (n= ). complete hemodynamic data, arterial and mixed venous blood gases, respiratory gas analysis (metabolic cart ccm, medgraphics) were obtained at baseline ( x) and twice (q. min) during leg mobilization. data were analyzed by anova. calcium channel blockers were used in complex preoperative preparation of hypertensive surgical patients. patients were allotted to groups based on their hemodynamic profile: hypokinetic: ejection fraction (ef)< . , patients; eukinetic (ef> . ),i patients and hyperkinetic (ef> . ),i patients. the most noticable change in hemodynamics was in the hypokinetic group: ef and cardiac output (co) were significantly decreased (p< . ) while systolic arterial pressure (sap) (p< . ) and peripheral resistance (pr) (p< . ) were elevated. the results showed that in hypokinetic patients on nifedipine ef (p< . t) stroke volume (sv) (p< . l) and co (p< . ) were increased while pr(p< . t), sap(p< . ) and diastolic arterial pressure(p< . ) were decreased. eukinetic type patients also showed an increase in ef,albiet to a lesser extent,than in the hypokinetic group. increased sv and co(p< . ) were observed in eukinetic patients though this was to a lesser extent than in the hyperkinetic group. in the hyperkinetic group of patients nifedipine had no effect on the aforementioned parameters except for a decrease in sap(p< . i). nifedipine increased ef in all hypokinetic patients. comparative results show that isoptin was less effective than nifedipine in decreasing peripl~eral vascular resistance and had a depressive effect on the myocardium. it can be concluded that the action of calcium channel blockers normalizing the circulation in the hypertensive surgical patient depends on: the condition of myocardium, the patients hemodynamic profile and their pharmacological properties. they were most effective in the hypokinetic group. zalo/nthinos e., daniil z. zakynthinos s., armaganidis a., kotanidou a., nikolaou ch..,roussos ch. critical care department, university of.athens, evangelismos hospital, athens, greece. introduction : surgical is the optimal treatrnent for ioculated effusions and the preferable procedure when multiple bands are seen in the pericardial sac by echo. patients : palients, post cardiac surgery, uremic ( men, women) with large pericardial effusion and clinical or echocardiographic findings of tamponade or both. these particular patients displayed numerous linear echo-dense bands and s~'ands crossing the pericardial space (in one of them a ioculated effusion compressed the left ventricule). one had aptt increased, four were mechanically ventilated. technklue : a fr polyurethane catheter with end and multiple side holes over ga needle was echo-guided to the ideal site (fluid abundant and closest to the transducer). the catheter was attached to a close system with a heimlich valve for continuous drainage (pneumothorax kit). subcostal entry was selected in one patient and chest wall in five. the patient's position was changed every hour at least. (we believe that the small changes in the position of the catheter and the mechanical breaking of the bands in relation with the movement of the heart assist the pericardial fluid to remove). results : in all cases only a small quantity of fluid was withdrawn in the first minutes( - ml) with some clinical and echo-findings improvement. the fluid was bloody or serosanuginous with high protein content (ht= % ,protein , gr/dl) in all cases. in first hours the mean volume of fluid removed was ml ( to ml). in that period echo showed no residual fluid. the catheter remained within the pericardium to days .. no complications are mentioned. conclusion : cardiac tamponade due to hemorrhagic high protein pericardial effusion in uremic and postcardiac surgery patients,, as it is revealed by echo dense bands, can be faced by -d echo guided perieardiocentesis. a -fr polyurethane catheter with multiple side holes, attached to a heimlich valve was effective to evacuate the pericardial fluid. no catheter was occluded though heparin infusions were not used. multiple changes of the patient's position may be fundamental. this -d echo guided pericardiocentesis performed in in~nsive care unit seems to be useful , safe and quick technique. determining the best inotropic drug represents a very serious problems. the use of more selective and potential inotropic and vasodilatative drugs does not always lead to improvement of hemodynamic parameters in patients with low cardiac output syndrome. this paper presents patients with acbp who need an inotropie support after extracorporeal circulation in first hours. the patients were divided into dobutamin et dopamine groups. the heart rate (hr). mean sistemic arterial pressure [map), central venous pressure (cvp). and termodilution cardiac index (ci) were measured. the measurements were without using inotropic drugs, and then using them after rain, min, and finally with one hour rate, within first hours. the statistical analysis shows that both drugs lead to an increase in hr in the first hour of the application. the final effect of dobutamine is no change in hr, whereas the effect of dopanime is very significant increase in hr. thus. an absence of taehyeardie response selects the dobutamine as a better choice. backeround: pulmonary vascular eadothelium possesses major metabolic functions, which when altered contribute to the development of serious pathologies such as ards. one such function is the conversion of angiotensin i to angiotensin ii, catalyzed by angiotensin converting enzyme (ace), located on the luminal surface of the endothelial cells. ace activity has been extensively studied in animals in vivo, by means of indicator-dilution techniques, providing: i) under toxic conditions, an early index of lung injury, and it) under normal conditions, estimations of dynamically perfused capillary surface area (pcsa). objectives: to validate the use of these techniques in matt: i) for pulmonary endothelial function assessment, and it) for pcsa estimation. methods: ace activity was estimated in ten adult haman volunteers, with no pulmonary medical history and normal pulmonary artery pressures, undergoing cardiac catheterization for coronary artery disease assessment. single-pass traspulmonary hydrolysis of the specific ace substrate hbenzoyl-phe-ala-pro (bpap; p.ci) was measured by means of indicatordilution techniques, and expressed as %metabolism (%m) and v=-hi( -m). bpap was injected as a bolus i) into a main pulmonary artery, and it) inside the right atrium, to assess ace activity in one and both lungs. we also calculated a,~,/i~, an index of pcsa. pulmonary plasma flow (fv) was determined by thermodilution. fp in one lung was estimated as . xf v. results: similar values of %m ( . + . vs . • and v ( . • vs . • were observed in both and one lung respectively. a~k~ decreased from • ml/min (both ltmgs) to :~ (one lung). conclusions: i) pulmonary endothelial ace activity and thus pulmonary endothelial function may be assessed in humans by means of indicator-dilution techniques, it) our data denote homogeneous pulmonary capillary ace coneentratious and capillary transit times in both haman lungs, iii) the % reduction of a=~/k~ in one lung suggests that this procedure can be used to quantify pcsa in man. (supported by the fonds de la recherche en saute du quebec and the national health system of greece). objective: verify whether antioxidant activity is higher in reperfused than in no-reflow myocardium after i.v. thrombolysis for acute myocardial infarction (ami). methods: patients with ami were included. blood for estimation of catalase (cat), glutathione peroxidase (gpx) and mn-superoxide dismutase (sod) was drawn before initiation of i. the mechanism of myocardial cell defence against free radicals is probably identical in both reperfusion and no-reflow phenomena. therefore, antioxidants cannot be used as reperfusion markers. objectives_ to evaluate the precipitating factors of hypothermic phrenic nerve injury following cabg with lima. methods: fifty two consecutive patients ( females), with a mean age of + (mean +sd) years were studied. during the ischemic arrest time topical hypothermia was obtained in al~ patients wffh ice slush and no cardiac insulation pad was used. all patients received a lima graft, with or whithout additional vein grafts. supramaximai, bilateral phrenic nerve stimulation was performed percutaneously preoperatively and whithin hours postoperatively. square wave stimuli of . msec duration were applied at the posterior border of the sternomastoid muscle. the compound muscle action potential of the diaphragm was recorded, using surface electrodes on the anterior chest wall. the time interval from the application of stimulus to the onset of diaphragmatic activity, phrenic nerve conduction time (pnct), was measured. values exceeding . msec were considered as abnormal. besults: preoperatively, all patients had normal (mean+sd) pnct, . • msec for the left nerve and . • mseo for the right nerve. on the first postoperative day, right pnct was normal in atl patients ( . • msec) , whereas left pnct was normal in patients ( . • msec) and abnormal in patients (incidence . %). in patients the left phrenic nerve was inexcitable and in patient left pnct was prolonged ( . msec). comparing patients with normal and abnormal pnct there was no difference in age, gender, number of grafts used, aortic cross-clamp and bypass time. however, patients with abnormal pnct had a lower preoperative ejection fraction ( • vs • p= . ). moreover, in all of them lima was dissected from its origin ligating all upper arterial branches, which provide the blood supply to the left phrenic nerve, whereas in those with normal pnct the small vessels originating from the upper to cm of lima were preserved (p= . ). conclusiojel~ a hypoperfused left phrenic nerve seems to be more susceptible to hypothermic injury during cabg with a lima conduit. objectives: to test if necessary interventions on systemic vascular resistance (svr) along with preset pump flew (q) during cpb could adversely affect autoregulatory response and cause vo shifts. methods: we studied males ( - yrs) who underwent cpb for cardiac surgery. at o oesophageal temperature - c we set pump flow at . i.m~ .min - . when map was higher than mmhg we calculated vo by using fick equation. then we infused sodium nitropruaside (sn) to control map at - mmhg for min and we calculated vq . without changing the sn infusion rate we set q at . i.m' .min " . ten min later we measured vo . we took vo changes into consideration if greater than %. statistical analysis using students-t-test for paired data and analysis of variance was used as appropriate. results: depending on the biphasic vo response to sn infusion during low and high q we classified pts in four groups (table). i. vo increases with sn and increases further during high q unmasking hypoperfusion and supply dependency. ii. vo increases with sn but the addition of high q results in systemic shunt. iii. vo increase during high q proves that vasodilatation can turn flow insufficient. iv. vo does not change with any intervention. the small number of pts and the wide standard deviation did not allow any statistical significance. conclusions: cpb is an interesting model for the behavior of microcirculation. intervention on svr and q can improve or impair effective regional oxygen delivery, resulting in either better perfusion or systemic shunt. vo monitoring seems necessary during cpb. preoperative cardiovascular optimization (opt) to ci > . l/min/m , _< paop < mm hg,and svri __< mmhg/ll/min/m decreases cardiac events (events) and mortality (mort) in peripheral vascular surgery patients (pvs). objectives: to determine if opt to the same endpeints decreases events in patients undergoing abdominal aortic aneurysm repair (aaar) and to study the r predictive value in pvs patients. methods: aaar patients and pvs patients were admitted to the s cu monitored with e pa and arterial catheters and treated to achieve opt. patients underwent surgery independent of success of opt data included demograph cs, incremental risk factors, laboratory and hemodynamic data pre, intra, a~nd postoperatively events, and mort. events included arrhythmias requiring treatment or prolonging the sicu stay > hours, a st depression > !mm or t wave inversion, an acute mr defined by a new q wave > . sec or cpk-mb > %. results are presented as means _ -. sd. opt was achieved in of ( %) and in of ( %) in the pvs and aaar group, respectively. events did nat differ between groups of ( , %) and of ( , %) in the pvs and aaar group, respectively (p>o. ). mort was of ( %) and of ( . %) in the pvs and aaar group, respectively (p > . ), while there was no difference in endpoints of opt between patients with and with.out events in the aaar group, there was a significant difference in ci between patients with and without events in the pvs group. of note, of ( %) patients who developed events in the pvs group had a ci < . in contrast to of ( %)in the aaar group. the positive and negative predictive value were % and % in the pvs and % and % in the aaar group. conciusione: f. the endpoints of opt used for pvs patients cannot be ~sed to reduce events in aaar patients; . pvs patients who have net achieved opt are at extraordinary risk of perioperative events; . preoperative card ovascu ar opt in aaar patients makes no difference in cardiac related events, background : comparison of the right and left filling pressures (cvp/pcwp ratio) is considered as a useful diagnostic clue : the normal ratio is _< . ; ratio >_ . may suggest right ventricul~ infarction while equalization of the cvp and pewp is a classic sign of tamponade ( ). however after cardiac surgery, many conditions (diastolic dysfunction, pulmonary hypertension, positive pressure ventilation) are susceptible to modify the '*normal" cvp/pcwp ratio. material and method : we determined cvp/pewp ratio in consecutive patients (pts) after uncomplicated cardiac surgery ( coronary artery bypass grafts; valvular replacements) measurements were made before and after tracheal axtubation. results :cardiac index : . _+ . /minlm~; laotate: + rag/i; cvp range : - rnmhg; pewp range : - mmhg. mean cvp/pcwp ratio before extubation is . ( % confidence imerval : . - . ) and after extubation, . ( % confidence interval : . -. . ), (ns, paired t-test). in % of the pts, cvp was higher than pewp. there are no correlation between the cvp/pcwp ratio and c! before (r = - . ) and after extubation (r = - . ) nor between the cvp/pcwp ratio and mean pulmonary arterial pressure (mpap), before (r = . ) and after extubation (r = - . ), discussion : cardiac performance is adequate according to ci and lactate. however the cvp/pcwp ratio is markedly higher than the "normal" (_< . ) ratio. this difference is not related to mechanical ventilation because the ratio is similar before and after extubation, nor to pulmonary hypetaension because of absence of any correlation with mpap, post-cpb diastolic dysfunction of the right ventricle could be an alternative explanation. in this group of pts, increased cvp/pewp is not associated with any impairment of cardiac performance (absence of correlation with ci), conclusions : cvp/pcwp ratio as high as within a large range of cvp ( - mmhg) and pcwp ( - mmhg) may still be considered as normal after cardiac surgery. this emphasizes the limitations of the hemodynamic monitoring after cardiac surgery (in comparison with echographic technics). careful analysis of the morphology of the cvp and right ventricular pressure curves (x descent, y descent, dip-plateau) is mandatory rather than relying on the quantitative assessment alone. reference : ( ) ntensive care.-university hospital -m~laga (spaink introduction. fibrinolitic treatment (ft) permits the treatment of acute myocardial infarction (ami) addressing the etiology, thereby eading to mproved ventncular function and a marked reduction m mortality. the main clinical oroblem is the reduced time of application. delay in hospitalization, which can be from to minutes, is potentially the most avoidable delay. method. to reduce delays in hospitalization, the following was carried out in two chases. audit: analysis of the time lapse from onset of symptoms to start of ft. showed that during "(he period june to december , patients with chest paros were treated within a eriod varying from minutes to hours from onset of symtoms. ages ranged from to (average , ), oelng males and females. they were glved initial ecgs to determine st mcreases suggesting ami. median t~me for this orocedure was l m.. potentia ami patients were then admitted to the coronary unit, [)atients, under age with no contraindications received ft the median time apse from admission to corona-y care and administration of ft was minutes ( . ), -he total median delay was minutes ~ -i h. min,~ delays n start of this procedure are grouped as follows: extra-hosdita delays (from onset of symtoms to arrival at hospital) diagnostic delays (from hospital arrival to ecg). treatment delays (from diagnosis to ft). objectives: protocol of procedure to implement a fast-track method. a protoco was drawn up with the object of reducing diagnostic delays to -i minutes and treatment delays to less than i minutes results. following rmplementatlon of this protocol in january , fts were glven, with an over all average delay of minutes. this fast-track method did not reveal any inappropnate ft or any increase m complications, conclusions: detailed study of the various times taken for diagnosis ane treatment of ami patients, showed up weaknesses in the system and improvements througn the protocol based on performence orocedures which led to a % reduction in the start of ft background: the importance of the early use of thrombo!ytic agents in acute myocardial infarction (ami) is based in the better remaining ventrictjlar function and smaller mortality rate because of the greater reperfusion and sma!ler infarction size, therefore, it is very impodant to apply this treatment to the maximum number of patients without thrombolytic contraindicati n, and within the minimun period of time. the "thrombolytic fast track" implementation allows to optimize the time to administrate thrombelytic agents avoiding multiple delays~ methodology: we anal!ze the application of thromboly c agents to patients with suspect of ami from the begin!ng of september until the end of february . in this time there are two different periods, during the first months thrombolytic agent were admin!strated at intensive care unit (icu), and during the second period we carried out a protocol of quick detection and thrombolysis therapy in susceptible patients at the emergency room in order to reduce the time to treatment. ma!n results are shown in the faffewins de ay h=hours m=minutes the implementation of the fast track does not need supplementary personal or equipment but a protocelized approach and training of the personal involved the main problem detected was the usual attendance overload of the emergency department that makes difficult to follow many structurated actions. conclusions: pratocqlized changes in the management of ami can significantly reduce the detay in the administration ef thrombolytic agents. it is not necessary to eomplet the procedure iq the emergency department, as the use of bolus schedules allows to begin the treatment in this area and to transfer the patient to icu afterwards. elective cardiac surgery. b calvet, f ryckwaert, p trinh duc, p colson. anesthesia -reanimation, hopital arnaud de villeneuve, montpellier, france. obhectives: the study was aimed at analysing the incidence of renal dysfunction following cardiac surgery and its prognosis (acute renal failure, post-operative morbidity and mortality). methods: two hundred and thirty seven patients (aged from to ) were consecutively operated on for elective cardiac surgery and retrospectively included in the study. patients with preoperative infections and operated on in emergency were excluded. each patient had preoperative invasive cardiac investigation with angiography and calculated ejection fraction (ef). anaesthesia, cardiopulmonary bypass (cpb) and cardiac arrest management were similar in all patients. general body temperature was reduced to - ~ c. renal dysfunction was defined as a % increase from baseline of serum creatinine. demographic data, asa, treatments, pre-operative creaunine level, cpb and clamping (axc) times, intra and postoperative use of inotrope, serum lactate level before surgery, at the end of cpb, at the time of admission in intensive care unit (icu) and on post operative day one and apache score were compared in patients with or without renal dysfunction using anova test for repeated mesures and x when appropriate. data are expressed as mean +__sd. p value less than . was considered statistically significant. results: thirtytwo patients ( , %) suffered from renal dysfunction. age, serum lactate level at the end of cpb, at admission in icu, at pod and apache level at admission in icu, intra-operative use of inotropes were statistically different in patients with or without renal dysfunction (p< , ). mortality rate was statistically different in patients with or without renal dysfunction(~, , % and %, respectively, p= , ). incidence of acute renal failure following renal dysfunction was , % ( patients required hemodialysis). conclusions: although our cdteria for defining renal dysfunction were very sensitive, the incidence of renal dysfunction following elective cardiac surgery was lower than communly accepted in the litterature ( ). however renal dysfunction appeared significantly associated with a poor prognosis. reference: -settergren g, ohqvist g current opinion in anaesthesiology , : - r ; , tzelepis, g. , , late complications were observed in % of cannulations: local infection in (i, %), catheter displacement by the patient in cases ( , %), catheter displacement during nursing care in ( , %) and malfunction in cases ( , %). conclusions: central venous catheterizations are followed by immediate and late complications in almost the same percentage acute poisoning with amphetamines (mdea) and heroin: antagonistic effects between the two drugs methods: after institutional approval and informed consent, selected patients ( _+ years) undergoing peripheral vascular surgery (n= ) or carotid endarterectomy (n= ) were investigated. patients included had either documented cad (n= ) or two or more (n= ) dsk factors (age > years, smoking, diabetes meltitus, hypertension, hypercholesterolaemia > mg/dl). -lead ecg recordings were carded out preoperatively, on ardval in the postanaesthetic care unit, and h, h, h, and h postoperatively. ecg recordings were analysed by an independent blinded cardiologist for signs of pmi (new st segment depression > . mv and/or new t inversion). in addition results: of the patients investigated developed ecg-documented pmi, % occurdng in the immediate postoperative phase. troponin i levels > . ng/ml were found in of these patients thus, comparing a cardiac troponin i cut-off level of ng/ml with intermittent -lead ecg recordings, we found a sensitivity of % and a specificity of % methods: demographic, clinical and ecg data were analyzed. . % of patients were male; . % female. cad was the most common underlying cardiac disease ( . %) and . % underwent open heart surgery. % received proeainamide for supraventricular and % for ven~cular arrhythmias. % received a loading dose. maintenance was provided by iv route in . % and by po in . % ( . %sr end . % ir). . % of patients were obese right ventricular function following cardiopulmonary bypass: is important the mode of myocardial protection we underwent this study in order to examine its safety and usefulness in pts with trustable coronary conditions (unstable angina ua the mean age for group a was • years, for group b • years, and for group c • years. a history of previous myocardial infarction was present in pts of group a, in of group b and in of group c. three pts in group a, in group b and in group c had previous coronary artery bypass grafting. the median time between the onset of symptoms and a was days ( - ) for group a we used a continuous fixed intravenous a infusion at a dose of the sn was % in groups a and b, % in c, and sp % for group a, (fixed defects included) and % for groups b and c. there was no difference of side effects among groups: chest pain (i pt -group a, pts -group b, and pts -group c), transient hypotension ( pt -group c), headache ( pts, group c), dyspnea ( pt -group a), while st depression was seen in pts of group b and in pts in group c. the rate of a infusion was decreased to /kgr/min in one group b pt due to development of chest pain s five year follow up of humoral immunity in paced patients athens polyclinic hospital, department of cardiology athens, greece author index a abiad ch bertschat, e betbes blanch, l del nogal saez e -meneza nolla, j. nolla-salas pilz~ u puig de la bellacasa e scarpa, n. van de wetering objectives: only % of patients suffering from acute guillain-barr@ syndrome (gbs) respond promptly to established therapies like plasma exchange or intravenous immunoglobulines. in contrast to serum, cerebrospinal fluid (csf) of gbs and ctdp patients contains enriched portions of antiexcitatory factors(i) and cytokines ( ) able to induce pronounced conduction block ( ). to reduce or remove such pathologic factors we introduced a technique with direct access to the subarachnoid space. methods: with informed consent we lumbally inserted g catheters in gbs-and cidp -patients under sterile conditions. some of them had not responded very well to established therapies. - ml of csf were withdrawn and retransfused by a bidirectional pump (flofors) after passing newly developed filters (pall). daily filtrations with several cycles were performed ( - ml) over one week. results: the gbs patients improved after days (median) for one grade (according to the gbs-scale from the gbs study group) . the ventilator dependent patients were weaned after days (median). patients not at all treated before ( / ) responded better than patients that had been pretreated ( / ) with plasmaexchange or intravenous immunoglobulines. / cidp patients drew benefit from treatment, stabilized iongterm. conclusions: csf-filtration is a relatively save and well tolerated additional procedure. the costs are considerably lower ( / ) than those for plasmaexchange or intravenous immunoglobulines. references:( )wsrz aet al: csf and serum from patients with inflammatory polyradiculopathy have opposite effects on sodium channels. muscle nerve ( ) . ( ) clinical observations were made in patients admitted to the clinic. they were in coma associated with acute alcohol intoxication.standard evaluations (ecg-monitoring, electrocardiography, neuromonitoring, studies of acid-alkali condition, biochemical and toxicologic investigation of blood and urine) prior to and following the treatment conducted were undertaken in all the patients.to correct irreversible impairement of functions twofold laser blood irradiation by means of alok- apparatus, the exposure within minutes, was carried out.the data obtained confirm more rapid coma withdrawal of the patients, reconstruction of the heart and central nervous system electrophysiologic indeces, reliable reduction in complications compared with the control group. objective: to know the actual incidence of the critical illness polyneuropathy(cip). setting: fourteen intensive/critical care unit beds, in bed university hospital, covering . inhabitants (majority rural area). the icu patients are medical, surgical and coronary, excluded the neurotrauma and neurosurgical. design: a conseculive and prospective study. all the patients admitted during three months, from january lth to march th , were eligible (patients with admittance diagnosis of polyneuropathy were excluded ). methods: patients with apache ii score > , at the admission and six days after admissions were included into the study protocol. diagnosis of sepsis, mof, and all the drugs administered days before were recorded. a complete neurological exam, by a neurologist, in absence of ssdatives and muscles reliant ( th, ~ and th days after icu admittance) was made. we evaluated the nerve and muscles function with and electromyography study in all patients, at same days. in some paeents with cip we performed a nerve biopsy. results: from patients ( apache ii score: . ) admitted in the icu, ( . %) enter the study protocol. seven ( , %) had an axonal polyneuropathy(cip), three very severe. only four of the patients with cip had pathologic clinical exam. apache ii score: cip vs non-cip was . vs . . the incidence of cip by diagnosis (cip/diagnosis) was: sepsis, / and mof, / . conclusions: . -we think that it is necessary to define the "critically ill" for some score, before designing a study to know the incidence of this syndrome. . -we think that the incidence of the cip is lower that the latest papers say. objectives:acute pancreatitis(ap)is becoming a more important problem among the elderly as the population ages. the increasing presence of gallstone disease,as well as the use of certain drugs,may also contribute to the occurrence of pancreatitis. methods:all patients(> years)admitted to our medical department over an eight year period were included.pancreatitis was confirmed by biochemical tests and imaging techniques.scores were developed using ranson's criteria and a multiple organ system failure(mosf)index . overall, patients were evaluated; ( %)had pancreatitis of unknown etiology . results:( )patients with pancreatitis of ~nlqnown etiology were sicker and had greater morbidity( % vs %),mortality( % vs %),and longer hospital stays than p~tierf~ with pancreatitis of known cause.( )the best predicto~of severity and outcome was the mosf index and not ranson's criteria;the higher the score,the greater the associated disease,the worse the outcome.( )curlously,no difference existed in associated medical conditions between patierts withknown and ur ~own causes of pancreatitis. conclusions:greater organ dysfunction exists in patients with pancreatitis of unknown etiology, even though age and associated medical conditions do not differ . the application of the total enteral nutrition in the burns disease has minimized the complication rate and consequently increased the survival rate of children and adults. time of initiation, composition, duration and way of administration are very important in obtaining the optimum beneficial effect from the treatment and diminishing the complication rate and side effects. the above features will be discussed in view of our experience in cases. ta buckle?,, ra freebalm, c gomersall g joynt, r young. tg short. department of anaesthesia and intensive cm+e, prince of wales hospital. the chinese university of hong kong, shatin, hong kong introduction: gastric mucosal ph (phi) monitoring has been proposed as a relatively noninvasive index of the adequacy of aerobic metabolism in the gut. to examine the accuracy of gastric intramucosal pit measurements as a function of time and as a function of the catheter itself to determine whether the measurement error between catheters is clinically acceptable. patients with a gastric tonometer (trip tm, tonometrics, worcester. ma) insitu for > days were studied. following informed consent two new tonometers were inserted equidistantly & correct position was confirmed radiographically. measurements of intramucosal gastric ph were then performed over a hr period. eight -ten measurements were made in each of ten critically ill patients.percent differences between the two new catheters were . % ie at ph . _+ . ( % limits) and between old & new catheters were . %, ie ph j _+ . ( % limits). conclusions: the results suggest that the function of the tonometer deteriorates over time and that the absolute values of phi m~ not ~ufficiently accurate. however as a trend monitor phi may be useful in the clinical setting. despite a continuous decline both in li'equency and severity of gastro-intestinal stress-lesion/-bleeding (gisb) due to both improvement in preclinical support and in intensive care medicine, patients with cerebral lesion are still considered at high risk for developing gis . therefore the question arises, whether m> specific (}lsb-prophylaxis besides general and neurological intensive care, specific pharlnaeothcrapy or even the combination of two specific drugs reveals any protective efli~ct on frequency and severity of gisb.this pntspcclive randomized study has been perfornted in patients snfrering t'rttna head-injury/cerebral lesion and with a glasgow-coma-scale on admission (gcs:,)of < . according to randomization the patients have been grouped as tbllows: h analgesia/sedation (n= ); ih analgesiajsedation plus pirenzepine mg/day (n= ); .[ih anatgcsia/sedalkm plus sncraltate x [ g/day (n= ); iv: analgesidsedatkm plus pirenzcpine mghlay plus sucralfate x e/day (n= ). slalislical analysis has been performed by chl:*tt~sl. rank correlatinn and unpaired t-test; statistical significance has been set with p < . . / patients ( . %) developed gisb. although the mean gcs~-value (x -+ sd) did not reach significance between patients with and without gisb ( . + . vs . -+ . ). a significant inverse correlation between gcs:, and the incidence of gtsb (rs~ = . ) has been shown. the frequency of gisb among the groups is as follows: h . %; lh . %; llh . %; iv: . % (ch -~ = . ; not signilicant). no gisb-induced blood translusion or mortality, respectively, could be demonstrated. survival rate between the groups did not differ significantly (chi-" = . ; p= . ) and reached an overall-value of . %.drug-specific glsb-prophylaxis -administered either as monotherapy (pirenzepine, sueralfate) or in combination of these two specific-drugs -reveals no additional significant influence on the incidence of gisb in patients with cerebral lesion compared to no specific prophylaxis besides the general trauma-/disease-specific intensive care measures. critical care dpt, evangelismos hospital, athens university scho~" of medicine objectives: the correlation of longterm presence of nasogastric tube (ngt) to gastroesophageal reflux (ger) is still in question. in case of positive correlation, peg should represent an alternative to tube feeding in patients unable to be fed orally. therefore, we investigated: i) the correlation between ng and ger and ii) the effect of peg on ger. methods: a -h esophageal ph-metry was performed in patients in recumbent position at ~ who had a ngt for more than days and were on sucralfate for gastric mucosal protection. the tip of the ph-probe was lied cm over the esophagogasttie junction, confirmed by x-rays. patients who presented a percentage of ger-total (i.e. with a ph less or more than ) (ger-t) more than %, underwent ~t peg. the presence of a creseent-notch on the esophagogastric junction persisting on inspiration and the grade os endoseopic and histologic esophagitis (scale= - ) was noted. two ph-metrles repeated on h and on days post-peg were compared to the pre-peg one, with the followin~ parameters taken in consideration: i) % ger-t, ii) number of ger-total per hour (no/h ger-t) and iii) the duration that ph was less than (tph< ). in case ot ger persistence at the ph-metry on ?th day post-peg (group ii) another endoscopy was performed, while patients with reduced ger (group i) were considered as esophagifis-free.results: out of patients presented a ger-t> %. eleven out of group i group (n= ) i ( objectives: the aim of the present study was to compare the performance of a specially modified version of a photo-and magnetoacoustic (pa/ma) gas analyzer (br~)el & kjaer, denmark) with a conventional quadrupole mass spectrometer (ms) (innovision, denmark) in inert gas rebreathing (rb) tests such as determination of functional residual capacity (frc), pulmonary capillary blood flow (pcbf) and lung tissue volume (vtc). methods : from simultaneous readings of inert gas concentrations with the ms and the pa/ma analyzer during rb experiments a comparison was made of the pcbf, vtc and frc values. the rb tests were performed during rest and exercise ( , and w) in ten healthy subjects. results: the differences (mean +/-sd) between simultaneous estimates of rebreathing parameters were the following (pa/ma -ms) for pooled data, pcbf: . +/- . i/min, vtc: - +/- ml and frc: . +/- . liters. conclusions: smell but significant differences were found between the estimates of pcbf, vtc and frc using the ms and pa/ma, respectively. reference: p. clemensen, p. christensen, p. norsk, and j. gr~nlund. a modified photo-and magnetoacoustic multigas analyzer aplied in gas exchange measurements. j appl physiol ; : - . objectives: because transcranial doppler (tcd) has been proposed to explore cerebral co vasoreactivity in brain injury (stroke ; : - ), we compared this technique with the kety-schmidt reference method to assess cerebral vasoreactivity in comatose patients. methods: mechanically ventilated patients (age - yrs, glasgow - ) in coma due to acute brain injury were investigated during stepwise changes in paco ( , , , and mmhg) by increasing inspired pco . middle cerebral artery velocity (vm) was measured by tcd. after insertion of a catheter in the ipsilateral jugular bulb, cerebral blood flow (cbf) was determined by the kety-schmidt method, using the inhalation of % n through the inspiratory line of the ventilator. for each patient a cerebral co~ vasoreactivity index was calculated as the slope of linear relationship between vm or cbf and paco . objectives: after cardiac surgery the fluid shill, between interstitial and intravasal space may be marked. this is due either to the intraoperative volume loading by the extracorporeal circulation or the increased postoperative diuresis. therefore, infusion of a large amount &fluids is necessary during the first postoperative hours. it still remains unclear which of the substances at disposal is the best for this purpose. aim of the present study was to compare the different fluids with special regard to postoperative bleeding and rheological behaviour. methods: patients undergoing cabg-surgery were investigated and randomizedly distributed to three different groups of postoperative volume replacement to stabilize the mean arterial pressure at mm hg. . ringer's solution, . . % gelatine solution, . % hydroxyaethylstarch (mean m.w. . ). we evaluated the following parameters within intervals of min: arterial and central venous pressure, heart rate, postoperative bleeding, urinary output, volume replacement. results: there was no statistically significant difference between the groups with regard to urinary output and bleeding. in spite of larger amounts of fluids necessary in the ringer treated group patients of this group showed symptoms of hypovolemia. hematocrit was increased in the ringer patients. this was statistically significant. introduction: pulmonary wedge pressure (pcwp) and central venous pressure (cvp) are frequently used as parameters for cardiac preload, although it is known that both are poorly correlated to the cardiac index (ci). it has been claimed that intrathoracic blood volume (itbv) measured with the thermal dye dilution method reflects cardiac preload better than pcwp and cvp. we studied the correlation between itbv and ci in a mixed population of critically ill patients. methods: in consecutive patients ( sepsis/sirs, acute heart failure, ards, transjugular intrahepatic portosystemic shunt) monitored with a pulmonary artery catheter, itbv was measured on regular intervals using the pulsion cold z- system (pulsion, munich, germany). ci, pcwp, and cvp were recorded simultaneously. results: a total of ol measurements was made. pcwp and cvp did not correlate to ci, nor did apcwp or acvp correlate to aci. itbv was correlated to ci in a non-linear fashion (f - , df = , p < . , (figure) ). aitbv was correlated to ac in a linear fashion (r = . , f = , df = , p < .o ). a rapid and efficient circulatory support system may save a patient in cardiogenic shock. left heart bypass with percutaneous and transseptal placement of the aspiration canuia simplifies the circuit and avoids the need for an oxygenator. we assessed this preclinical set-up in anaesthetized pigs using a centrifugal pump with a f arterial catheter and a f left atrial aspiration line. animals were supported for two hours at a mean flow of . liter ( ' rpm), a mean hematocrit of % and low heparinisetion (act double baseline). hemodynamic and laboratory samples were taken at baseline (a), minutes (b), one hour ( pulmonary hypertension (ph) usually involves obliteration and loss of functional pulmonary microvasculature. the microvaseular endothelium normally acts as a major metabolic organ, converting angiotensin i to angiotensin ii via the angiotensin-converting ectoenzyme (ace). it is unknown whether the loss of functional vasculature and altered pulmonary blood flow seen in ph will affect lung ace metabolic activity. we therefore estimated pulmonary vascular ace activity in patients with ph of various causes: primary; post atrial septal defect closure (asd); chronic thromboembolic (te); anorexigen; iv drugs; collagen disease. single-pass transpulmonary hydrolysis of the specific ace substrate h-benzoyl-pbe-ala-pro (bpap) was measured and expressed as % metabolism (%me . we also calculated an index of peffused functional capillary surface area (amax/km). all patients with ph had an abnormality of %met or amax/km, or both. as compared to control humans (mean %met = . % _+ . % s.d.), the mean %met in ph patients was . % _+ %. the %met in ph patients correlated inversely with cardiac output (r= . ), possibly reflecting more complete bpap hydrolysis with longer pulmonary transit times. amax/km was markedly decreased in ph ( + ml/min) as compared to controls ( _+ ml]min), consistent with a significant loss of functional capillary surface area. patients with collagen disease, asd and anorexigen-induced ph had the most marked abnormalities. in conclusion, patients with pulmonary hypertension have decreased pulmonary endothelial angiotensin converting enzyme activity, likely due to a loss of functional or perfused pulmonary microvaseulature. supported by the funds de la recherche en same du quebec and the national health system of greece. objective: to investigate adrenocortical function in patients with ruptured aneurysm of the abdominal aorta (raaa). studies investigating adrenocortical insufficiency in critically ill patients report an incidence ranging from % to less than %. this may in part be explained by difference in methods used (single cortisol measurement vs short acth stimulation test) and populations studied (heterogenous groups of patients with great individual variation in underlying disease as well as duration and severity of illness). methods: we investigated the adrenocortical function in patients with (raaa).a short acth stimulation test (synacthen test; ug - acth iv) was performed at hrs within hrs of admission. plasma cortisol was measured before (cort basal) and after stimulation (cort stim). a plasma cortisol level > . umol\l before or after stimulation was considered normal, severity of illness was assessed using apache ii. results: of the patients investigated died and survived. mean cort basal in nonsurvivors was significantly (p< .o ) higher than in survivors; . (range . - . ) vs . (range . - , ). this difference between nonsurvivors and survivors was also present for cort stim but lacked significance; . (range . - . ) vs . (range . - . ). while patients showed a cort basal < . , no cort stim < . was found. there was no significant difference in mean age or apache ii score between survivors and nonsurvivors; vs and vs . conclusions: single plasma cortisol levels were inadequate to assess the adrenocortical function in the patients studied, judged by a short acth stimulation test, our investigation in patients with raaa showed no adrenocortical insufficiency. mortality in raaa is associated with elevated plasma cortisol levels. obiectives: mortality in acute myocardial infarction (ami) prinicipally depends on hemedynamic impairment. thus, patients (pts) with elevated pulmonary wedge pressure (pwp) present high in-hospital mortality. however, the complete right heart catheterization is laborious, so the central venous pressure (cvp) alone is frequently used to assess the severity of ami. the accuracy of cvp in estimating pts with ami was tested in this retrospective study. methods: pts. aged + years, admitted to our ccu from to with their first ami, were inctuded in this study. all had undergone right heart catheterization because of overt or suspected heart failure. swan-ganz catheters ( f, cm, abbott, il, usa) had been used, every treatment had been temporarily interrupted l h before the calheferization. based on ecg findings the pts were retrospectively divided into groups. in group a we included pts with anterior ami, in group b, pts with inferior ami, and in group c, pts with inferior and right ventricular ami. the initial values of cvp and pwp were considered for the linear regression of the pwp variable on cvp and p< . was accepted as statistically significant.results: in g~oup a, the cvp and pwp vaiues were + mmhg and _+ mmhg respectively. despite the signifanf correlation (p< . ) between the two variables, it was not possible fo predict the exact value of pwp based on cvp value, pts ( %) presented cvp> mrnhg and of these ( %) had pwp_> mmhg. in group , the cvp was _+ mmhg and the pwp, _+ mmhg. significant correlation (p< . ) between the two variables also existed, however it was impossible to predict the pwp value. pts ( %) had cvp> mmhg but only of these ( %) had pwp> mmhg, similar was the relation between cvp and pwp in group c (p< . ). cvp averaged + mmhg, and pwp, _+ mmhg. pts ( %) had cvp> mmhg and from these ( %) presented pwp> mmhg,conclusions: a single measurement of cvp in ami does not ensure an accurate assessment of pwp. because every pt with ami needs optimal values of pwp in order to prevent pulmonary congestion or manifestations of low preload, the significance of complete right heart catheterization becomes apparent. in patients (pts) with advanced hf the need and the prognosis for heart transplantation (ht) can be predicted from vo= max. indirect measure of functional capacity with the six-minute walk test can also predict smvival in moderate hf. to predict vos max from indirect astinmtions of functional capadty such as - ~q~/, pulmonary and heart function tests, and to assess the prediddve value of the above parameters in hf pts survival. we evaluated pts (age + yeats nyha class: ii, hi, iv) with hf for pit. they underwent a pmgmmive exercise test on cycle ergometer for vo max determination, a -mw, a right heart catheterization and a spirometry and dlco estimation. introduction: brain death causes myocardial impairment by mechanisms that are not well understood yet. the aim of this work was to assess the echocardiographic features found in these patients from the clinical onset of brain death to somatic death, methods: seven brain dead patients were studied (patients" relatives refused to allow them to be used as donors). mean age was . ( - ) years old. four of the patients were female, none of the patients had any history of cardiac disease. transthoracic echocardiogram (echo) and electrocardiogram (ecg) were obtained at the onset of clinical brain death and were repeated every hours until somatic death. we we detected severe diffuse hypokinesia (ef< %) in patients and mild hypokinesia in others (ef - %). systolic function was strictly normal in only patients. corrected qt interval (qtc) in ecg was . _+ . msec (normal range - msec) just before somatic death (b). conclusion: in patients with brain death we observed a significant increase of left ventricular mass due mainly to ivs "hypertrophy" without any important change in the dimensions of the left ventricle. to our knowledge, this finding has never been reported before and its importantance in heart transplantations may be of particular interest. predict right ventricular outcome. l. jacquet, r. dion, p. noirhomme. m. van dijck. m. goenen cardiothoracic intensive care unit, st-luc univ. hospital(ucl) we have registred: heart rate (hr), blood pressure (bp), pulmonary artery pressures (pap), central venous pressure (cvp), pulmonary capillary wedge pressure (pcwp), pulmonary and systemic vascular resistances (pvr, svr), right ventricle end-diastolic end end-systolic volume (redv, resv), right ejection fraction (ref), right sistolyc ventricular work (rsvw) and cardiac output (co) using a thermodilution thechnique and a microprocessor (model ref- ; baxter-edwards laboratory); duration of cpb and aortic clamping, and the requirements of haemodynamic support after cpb.results: in the c group an increase post-cpb of the fc ( + . + . , p < . ) was produced without significantly changes in the redv, resv, ref, rsvw neither co. in the w group, hr increased from . + . to . + . (p < . ); redv was reduced from . -+ to . _+ . (p < . ); resv was reduced from • . to + . (p < . ). there were not changes in the other haemodynamyc parameters. there was a trend (no significantly) to an increase of ref in the w group ( . + . |• . ) compared with the c"group ( • . ($ . • . ) post-cpb. the need for haemodynamic support was similar in both groups.conclusions: the warm, continuous, anterograde-retrogade myocardial protection has obtained a decrease of preload, hr, and a trend to an increase in the ref, making an improvement in the right ventricular global performance when is compared with the classic form of cold myocardial protection. objective: to evaluate the effect of dobutamine on gastric mucosal ph (phi) after coronaly artery bypass surgery. design: prospective study in a university hospital intensive care unit (icu). subjects: elective cardiac surgery patients. interventions: dobutamine was infused at ug/kg/min for hours immediately after admission to the icu. hemodynamics were measured every minute periods until hours and again hours after stopping dobutamine. results: there were no significant differences in mean gastric phi between the groups but mean phi decreased in both groups during the study period. oxygen delivery and consumption both increased during dobutamine infusion but decreased to the control group level after stopping the dobutamine infusion. lactate levels did not change. baseline objectives: the aim of the study was to evaluate the usefulness of a low dobutamine dose in conjunction with intraaortic balloon pumping and mechanical ventilation in cardiogenic shock. we studied patients . -+ t . years of age suffered of post infarction cardiogenic shock characterized by a systolic arterial pressure< mmhg, urine output< ml/h and mental confusion or purpueral signs of low output, non responded to dobutamine infusion up to pg/kg/min. all patients underwent mechanical assistance by the intra-aortic balloon pump (iabp). five patients were additionally placed on mechanical ventilation due to blood gases disturbances. the end points in our study were: reversion of cardiogenic shock, improvement of patients survival or both on the th post infarction day and months later. results: three patients refused iabp treatment and / survived on the th day. on the th day / supported by the iabp and / that underwent mechanical ventilation plus iabp were alive (p < . ). on the th month / supported by the iabp and / that underwent mechanical ventilation plus iabp were alive (p< . ). conclusions: in conclusion, the combined use of mechanical ventilation and iabp assistance in severe cardiogenic shock might improve survival. obiectives: the study was aimed at analysing predictive factors of swan ganz pulmonary catheter (pc) requiremen t during elective cardiac surgery according to the need of sustained inotropic support after surgery. methods: three hundred patients (aged from to ; females and males)were consecutively operated on for elective coronary artery bypass surgery (cabg, n= ), valvular replacement (vr, n= ), combination of both (vr-cabg, n= ), or others (n= ) and retrospectively included in the study. each patient had preoperative invasive cardiac investigation with calculated ejection fraction (ee). anaesthesia, cardiopulmonary bypass (cpb) and cardiac arrest managements were similar in all patients. pc requirement was estimated from the need of either dobutamine, adrenaline, dopamine or enoximone use during the first hours after cardiac surgery. demographic data, asa and nyha classifications, preoperative ef and treatments, type of surgery, cpb and aortic cross clamping (axc) times, and postoperative incidence of complications were compared in patients with or without inotropic support using either student's t test or x with continuity correction when appropriate. results: seventy hree patients ( . %) required inotropic support after surgery. axc .and cpb times, mean stay in icu were significantly longer in patients with inotropie support (p< . ). type of surgery, preoperative ef, and nyha classification are the first significant factors related to inotropic support (p< . ). most patients operated on for double-vr or vr=cabg required inotropic support ( and %, respectively). postoperative mortality was higher in patients receiving inotropic support ( , % vs , % 'overall mortality, p= . ). conclusions: since pc insertion is most.often justified because inotropes are required, these results suggest that elective rather than routine systemic pc insertion could be helped by considering several but selected preoperative factors. background: cardiovascular depression due to anaesthesia, old age and major gastrointestinal surgery is becoming an increasingly frequent challenge .to the anaesthesia-surgory team. deliberate preoperative manipulation of haemodynamics and oxygen transport parametres towards prede~t~mined optimal values may prove to be effective "in reducing morbidity ~nd mortality in high risk surgical patients,. a new concept of using conlimaous perioperative measurement of cardiac'output to obtain and maintain supranormal oxygen delivery (do i) is presented. methods: continuous measurement of cardiac output is a relatively new form of on-line monitoring, in which trains of impulses are emitted from a thermal filament mounted on a pulmonary artery catheter. computer software recognizes patterns generated by minute changes in blood temperature and ealoalates cardiac output every - seconds. cardiac output and mixed venous blood oxygen saturation are displayed graphically on line. in tins tm study cardiac output was measured continuously by vigilance cardiac outpu t compl/ter (baxter). preoperative haemodynamic optimization was performed with the goal of increa- sing do i to at least ml/min/m accordfing to shoemaker's algorithm . this was.done by infusing colloids (albumin or hydroxy ethyl starch (haes-steril| until the desired do was reached. infusion was stopped if cardiac output ceased to increase with infusion, if there were signs of pulmonary oedema or if wedge pressure reached mmhg. vasoactive or inotropic drugs were infused if the desired do was not reached by infusion alone. anaesthetic technique included continuous thoracic epidural and isoflourane anaesthesia. expected mol:bidity and mortality rates were calculated by the "possum" score aasing preoperative clinical and paradinical estimates of organ function as well as surgery characteristics . materials: asa group ill-iv patients with a mean age of years (range - ) and a mean weight of kg (range - )) scheduled for major abdominal surgery were included. results: patients were excluded because do i could not be raised at all. mean do i was increased from ml/min/m (range - ) to ml/min/m (range - ). mean volume of preoperativdy infused colloid was ml (range - ). during surgery ml (range ) of colloid was infused. mean length of surgery was minutes (range - ). mean blood loss was ml (range ). expected mortality and morbidity rates ("possum") were % and %, respectively, whereas patient follow up upon discharge or at death revealed mortality and morbidity rates of % and %, respectively. conclusion: based on experience from the present study, continuous measurement of cardiac output has proved to be a valuable tool for perioperative optimization of do in asa group ili and iv patients during major surgery. however further studies including a greater number of patients are necessary to confirm the promising preliminary findings. we studied the hemodyn~c effects of three different combinations of positiv inotropic .agents, vasodilators, diuretics and av-filtration (av) in patients (pts) with severe left heart faille (left veutrieul x filling pressure (lvfp) > mmhg) due to acute myocardial infarction. hemodynamic measurements (intravascular pressures (lvfp), thermodilution (cardiac index (ci)) were made before (control) and after each therapy. in furosemide (f) + d butamin (d) + nitroglycerin (ni) reduced lvfp and a small increase of ci occurred. in of these pts :(group a) nitroprusside (hip) instead of ni increased ci significantly, in the other pts adding of amrinone (a) resulted in a pronounced increase of ci. group c (n= ): the combination of ni and av reduced lvfp but did not increase ci which was achieved by av+d+ni. in order to optimize the treatment of acute heart failure a combination of inotropic agents, vasodilators, diuretics and av-filtration should he used guided by hemodynamic monitoring. arias jr, miragaya d, sandard, san pedro dm ~, herndndez d, valenzuela . objectives: to evaluate the variation in nomdrenaline (na) plasma concentrations in patients with acute myocardial infarction (am ) after thrombolytic therapy with noniltvasive reperfusion criteria (clinical, electrocardiographic and enzymatic), in relation to infarct size and location.methods: consecutive patiens with ami, from october , to february , , admitted within hours alter onset of symptoms, undergone successfull systemic thrombolysis. of them were anterior (group a) and inferior (group b) . noradrenaline plasma levels at (na ), (na ) and (na ) minutes after admission were compared with ck-peak plasma levels by linear regression. differences were tested for significance by student-t-test for paired and unpaired values. na plasma concentration was measured by high-presssure liquid chromatography. p< ns . ns means -sem (normal limit for our laboratory: na < / pg/ml; ck < u/i ) conclusions: . the na plasma levels at admission (nai) are more increased in anterior than inferior amis, probably in relation to infarct size. . the decrease in na is more evidence in amis with anterior location. . this decrease is probably due to the major efficacy of thrombolytic therapy in amis with anterior location. arias jd, miragaya (group b) , probably due to certain degree of t~cg'rfueion. . there is not significant variation in na in conventional treated ami (group c). v.suchanov, a.levit, p.trofimov, icu, regional hospital, ekaterinburg, russiaobjectives: our task was to improve the technique of preservation of platelet rich plasma. methods: patients scheduled for multiple cardiac valve replacement in were divided into two groups: group i ( patients) -without pp; group ii ( patients) -pp was performed preoperatively. the first pp was made ten days and the second - days before the operation. prp was preserved by cryoconservation. our technique of cryoconservation is distinguished by the speed of freezing ( - ~ and absence of dmso. this made it possible to preserve % functionally active platelets during days. the prp was transfused back after heparin neutralization. the hospital ethics committee approved the investigation.results: the blood loss through the st p. o. d. was significantly greatest in the group i ( _+ ml) and all the patients required transfusion of the donor blood ( + ml) whereas the blood loss in group ii was +_ ml and olny patients required the donor blood. the number of platelets on the st p.o.d, was _+ . /l (group i) and + . /l (group ii), p < . .conclusions: our technique of prp cryoconservation makes it possible to avoid the crystallization phase during freezing of prr thus the infusion of prp may improve hemostasis after open heart surgery and limit the use of the donor blood. in-hospital outcome of women suffering an ami is generally considered worse than that of men, but it is still debated whether female sex is per sea negative prognostic factor or is merely associated with other negative determinants of prognosis. the purpose of the present study is to evaluate the independence of the association between female sex and mortality (in the patients of the swiss centers) and in the patients randomized in the isis- trail mortality rate in women was . % ( / ) compared to . % ( / ) in men; in switzerland: in-hospital mortality for women was . % ( / ), for men . % ( / ).the table shows the results of isis- in terms of odds ratios and their % confidence intervals either after unadjusted analysis or after adjustment for age, known to be the major confounding variable when prognosis of women after myocardial infarction is considered, and for all the available clinical and epidemiological characteristics collected at trial entry: these observations suggest that there is a small but independent effect of female sex on short-term mortality after acute myocardial infarction. ( ) and bubble ( ) oxygenators a, ere used. anaesthesia was balanced and pts were extubated to hrs after cpb. pts were monitored with swan-ganz catheters (sgc) for hrs after cpb. at that time qs/qt was calculate( according to )be standard shunt equation. after the sgc had been removed, an estimated shunt was calculated. measurements of qs/qt were performed: before induction of anaesthesia ( ), after induction of anaesthesia (i[), mins after cpb (iii) (iv) and (v) hrs afiter cpb, rains after extubation (vi), hrs after cpb (v[ ) and on the nd, rd, th, th and tb postoperative day (pd) (viii, x, x, xi, xi , respectively). analysis of data was performed by two-way analysis of variance, p < . being regard as significant.results: the figure shows the values for qs/qt expressed as means + sd. there was a significant increase in qs/qt above b~setine throughoul the whole investigated period except on the th pd. qs/qt reached maximum at rains after extubation (vi). objectives: many stndies have shown advantages of membrane oxygenalors over ubbie type oxygenators. the aim of this study was to evaluate the influence of x 'genator type on pulmonary shunt (as/at) after coronary surgery. methods: patients (pts) gave their informed consent to the study which was approved by the university ttuman research committee. pts were divided into two groups: a (n = ) with a membrane o~genator and a (n = ) with a bubble oxygenalor used during cardiopulmonary bypass (cpb). ths were monitored with swan-ganz catheters (sgc) for hrs after cpb. at that tfme os/ot was calculated according to the standard shunt equation. alter the sgc had been removed, an estimated shunt was calculated..measurements of os/qt were performed: betore induction of anaesthesia (i), mins after extubation ( ), hrs alter cpb ( ) and on the nd, rd, th, th and th postoperative day (iv, v, vi, vii> viii, respectively). analysis of data was performed by one-way analysis of variance, p < . being regarded as significant.results: the figure shows the values for qs/qt expressed as means _+ sd. os/qt was significantly greater at rains after extubation (ii) in a group. the difl'ereuce between the two groups was no more significant from hrs after cpb (iii) to the end of the investigated period. ! i * p < a. s betw~n ~o~ conclusions: membrane ox 'genation during cpb is accomplished by reduction in blood cellular destruction and less alteration in blood. the results of our study show the influence of oxygenator type on value of qs/ot only after extubation ( to hrs after cpb). the difference in qs/qt disappeared his after cpb and since that time the oxygenator type had no influence on qs/qt. it may be of particular importance in patients with severe forms of cardiopulmonary disease who are at risk of higher postoperative morbidity and mortality. objectives: hypomagnesemia has been reported with a variable prevalence ( to % ) in icu patients. magnesium deficiency can induce a number of climcal symptoms (primarily cardiovascular and neuropsychiatric) but can also be clinically silent ( - % are asymptomadc), methods: we measured whole blood ionized magnesium (lmg++) in patients on admission to the icu, using a nova electrolyte analyzer (nova biomedical), containing an img++ electrode. blood was collected in syringes with dry heparin (radiometer qs ). normal range of img++ was found between . - . mmot/l (healthy volunteers). results: for the entire population, we found a % prevalence ( / ) of hypomagnesemia (figure ) . among the surgical patients, the prevalence was highest after cardiac surgery ( %) and after thoracic surgery ( %) and was lowest after neurosurgery ( %). hypomagnesemia was also common in patients after liver transplantation (lvtx) or with hepatic failure ( % for both groups). conclusion: our findings confirm that hypomagnesemia is common in acutely ill patients, especially in those after cardiothoracic surgery or those with liver disease. nevertheless. it is difficult to define the associated factors with sufficient specificity, so that measurements of img++ are warranted to diagnose hypomagnesemia. hepariu influences platelet function and may lead to thrombocytopenia called heparin-associated thrombocytopenia (hat) regardless of the dose and route of administration. additinnal venous and/or arterial thrombosis may lead to life-threatening complications. the incidence of so-calied heparin-associated thrombocytopenia and thrombosis (hatt) ranges between i- %. hatt is confirmed by a heparin induced platelet activation assay (hipa). results: from / to / consecutive patients of our icu were reviewed retrospectively. all patients were treated with heparim the incidence of hatt was % ( ). in all cases diagnosis was proven by a positive hipa. / patients died. in / hatt could be confirmed before severe thromboembolic complications occured. / patients developed a deep vein thrombosis (dvt), / dvt and pulmonary embolism (pe), / dvt, pe and arterial thrombosis (at) and / a dvt, pe~ at and a sinus thrombosis. conclusion: the incidence of hatt in a r series of pts. is %. presence of thrombocytopenia and thrombosis of the great 'vessels is associated with a significant mortality ( / ). computed tom graphy (ct) and transthoracic/transesophageal echocardiography (tte/tee) are important tools in diagnosing and monitoring the extent of cenlrai venous and arterial thrombosis. a. cabral md, m. shahla md c. meneses-oliveira md and jl vincenl md.phd. department of intensive care. erasme university hospital, brussels, belgium objective: to determine extreme hemodynanuc patterns in cardiogenic shock. although ~.~xdiogenic shock is characterized by a low cardiac index (ci), high systemic w~,scular resistance index (svri), and high cardiac filling pressures, some patients may develop art atypical pattern. we reviewed the hemodyuamic pattern of patients with cardiogenic shock, as defined by an initial ct below . l/rain/m: in the presence of myocardial dysfimction attributed to ischemic heart disease (n= ), heart failure (n= ), valvulopathy (n= ) or recent cardiac surgery (n= ). after exclusion of patients with concurrently suspected/documented infection, this study included patients, of whom ( . %) survived. treatment of shock included dopamine (n= ), dobutamine (n= ), norepinephrine (n= ) and epinephrine (n= ). patients with arterial hypertension (ah) and initially law plasnla renin activity (pra) had been studied. in all patient changes of arterial pressure (ap) after single administration of enap was studied. nypotensive reaction wiht deereasin e of average ap about - mm hg ayter single drug administration observed only in patients. ezap monotherapy accomplished during one week with mg daily dose. hypotensive effect observed in patients including ones which were susceptible to single enap administration. after that first stage of therapy all patints began to combinate enap with hypothyazid in dose of mg per day~ after week of treatment such drugs combination lead to veritable ap lowering in addition patients. in the remaining resistant to such drug combination patients was add corinfar in daily dose of mg. this new drug combination permits to lower ap in patients. subsequent discontinuation of enap administration to such patients aid not connected with increasing of again.therefore the most of the patients with ah and law pra( , %)did not susceptible to enap therapy and enap and hypothyazid combination. on the contrary-combination of corinfar with hipothyazid was effective in % patients with ah and low pra. methods: in patients with cardiogenic shock due to ischemic heart disease (n= ), heart failure (n= ) and valvulopathy (n= ), hemod aamic data including measures of intravascular pressures, cardiac output and mixed venous gases were collected at regular times intervals, at least times a da?. all measurements were obtamed in a relative steady state and in the absence of severe anemia or hypoxemia. treatment of shock included dobutamine (n= ), dopamine (n= ), norepinephrine (n=i ) and epinephrine (n= objective: based on our previous studies of the function of isolated liver grafts, this experimental protocol aims at developing a novel extracorporeal liver support circuit, with an incorporated pig liver. methods:the graft liver was obtained from pigs weighing - kg. under general anesthesia the aqimals underwent total hepatectomy,following cannulation of the portal vein, the infrarenal aorta and the infrahapatic vena cava and peffusion wit h it of heparinised r/l solution at ~ the circuit consisted of the graft liver connected to a fluid reservoir and a centrifuge pump. ten healthy pigs weighing - kgr were connected to the circuit as follows: the rt carotid artery was connected to the portal vein of the graft and the rt jugular vein was connected to the fluid reservoir, through the centrifuge pump. the fluid reservoir collected the outflow from the graft's suprahepatic inferior vena cava. the cystic duct of the graft was ligated and the bile.duct cannulated for bile collection and measurement. bridges were adapted to the circuit to bypass the graft liver when necessary, in cases of by pass blood perfusing the graft was oxygenated through a bubble oxygenator. mean total priming volume of the circuit was ml. temperature was maintained at ~ and portal vein pressure at ( - ) mmhg. the flow was . - . ml/gr of graft liver mass per minute. observation period was hours (t ). results: results of the hemadynamic and metabolic monitoring of the recipients [map (t = mmhg , t = mmhg), hr (t = , t = ), rap (t = mmhg , t = mmhg), pap (t = mmhg, t = mmhg), pcwp (t = mmhg, t = ~mhg), svr (t = dyn'sec/cm ' , t = dyn'seclcm~ pvr (t = dyn.sec/cm o, t = dyn.sec/cm ,'~), co (t = . t/min, t = . t/min), do (t = ml/min, t = . ml/min), vo (t = ml/min, t = ml/min), o er (t = . %, t = . % ), ph (to= . , t = . ), po (t = mmhg, t = mmhg), pco (t = mmhg, t = mmhg), pvo (t = mmhg, t = mmhg), svo (t = %, t = %), be, na, k, ca ++, lactate, osmolality, ast, alt, pt, aptt, revealed hemodynamic and metabolic stability of the animal. consumption, co production and tissue oxygenation of the graft were also studied. conclusion; the described circuit proved to be safe and well tolerated by healthy animals but its value for temporary liver support is currently being estimated, in a surgically induced experimental fulminant hepatic failure modal. introduction: prosthetic materials like silikone, dacron, teflon e.tc. produce auto immune responses and may even trigger clinical syndromes like scleroderma, sjogren, sle el.c. in our study we followed the evolution of humorial immunity parametrs for up to five years in a cohort of paced pts with implanted metallic and silicone materials. method: paced pts (mean age +- yrs) without clinical or laboratory findings of malignancy or immune disorders were included. we measured the immunoglobulins, the complement, the auto antibodies and the proteins involved in inflammatory reactions every months. the initial and final mean values are shown in the obiectives: hsp, a systemic leucocytoclastic vasculitis and anaphylactoid purpura can be accompanied by abdominal pain and life-threatening intestinal bleeding. recently we could disclose, that these patients develop severe fxiii-deficiency and immense haemorrhagic oedema of the intestinal wall. by the following case report we will demonstrate and discuss the importance of fxiiideficiency for pathogenesis, therapy and outcome in hsp. case report: a year old man developed typical skin manifestations of hsp following an episode of severe (biliary ?) pancreatitis and percutaneous draining of a pancreatic pseudocyst. two days later he had a paralytic "ileus with immense hemorrhagic wall-oedema and massive dilatation of the small bowel. he got fever up to . ~ and developed severe gastrointestinal haemorrhage (blood transfusions necessary). the coagulation data disclosed a severe fxhi-deficiency (activity %), whereas quickvalues, platelet count and atiii-level were found to be within the normal range. elastase was markedly elevated. substitution of fxiii to normal levels leeds to the cessation of bleeding symptoms and abdominal pain, later resulting in a restitutio ad integrum. conclusions: hsp with intestinal involvement is a life-threatening vasculitis, in which careful and frequent examinations of the coagulation system, especially of fxiii are necessary. detailed analysis of the coagulation data suggest, that the severe fxiiideficiency is due to a specific degradation by proteolytic enzymes (like elastase) as well as consumption within the immense haemorrhagic oedema of the intestinal wall. knowing these facts, even most severe cases of hsp with intestinal involvement can be successfully treated by substitution of fxih. a -year-old woman presented a year history of occasional self-limited episodes of weakness, generalized edema and o!!~aria. the immunologic testing showed no~nnai levels of complements, clq inhibitor, and serum chemistry values, between or during a attack, she was not treated. she was a~mitted to the hospital with symptoms including nausea, vomiting, weakness and ol!guria. on examination, the patient presented facial and g~neralized edema. the systolic blood pressure was mm hg, pulse beats/mir~ute, hematocrit . , seln~n protein /i, and se~um albumin q/l. an leg-kappa pa[apfotein was demostrated ( . g/l) and urine was neaative for puotein. c~'stalloid and colloid don't increased the blaod pressure but resulted in anasarca, with a total of ii lit[as of in~ravenous fluids. therapy wink flozen plasma, . units of clq inhibitor, cortlcosteroids, annihistwnines and antifibrinolytic agents was uns~iccessfull. the a~minist~ation of dopamine, norepineph~ne and epinephrine was inefective. the patient died at the bores, only a few cases have been reported, all had igg paraprotein, the pathophysio!o~] is urd~no~n% but is possible that the paraprotein may be zesponsib!e for the increased capillary pe~leabilityo despite efforts to res~scinate the patients during an acute attack, the syndrome is often fatal. the variable course of systemic uapiliary leak syndrome and the unpredictability and self-limited nature of attacks cloud assessment of therapeutic inte~-vention. the purpose of the present work is to provide some information about the nursing care and results from our experience in continous arteriovenus hemofiltration (cavh).cavh is an extracorporeal technique, especially applicable in the critically ill patients, for disturbances, and for the control of azotemia.we used this method in critically ill patients men and women ages from - who had sepsis -arf congestive heart failure postoperative multiple organ failure and polytrauma .this method was applied to these patients from to hours. % of the patients recovered completely their kidney function, % improved their kidney function and % died.we concluded therefore that this method was very effective for the critically ill patients to whom it was applied, but it requires excellent and continuous nursing care; under the above mentioned circumstances the method works effectivelly. an animal model with rats undergoing a dialysis procedure was designed to test the hypothesis that recovery from ischemic acute renal failure (airf) may be affected by the type of membrane used in hemodialysis. male sprague dawley rats were allocated to groups: in group i, (n= ) airf was inducted by bilateral renal artery clamping for rain. group h (n= ) rats underwent a sham procedure. in each group, rats were dialyzed twice ( th and th day) with either a cuprophan (cupro), a hemophan (hemo) or a pan (an ) minidialyscr or stayed nondialyzed (no hi)). renal function was monitored daily by measuring urea and creatinine values and by two single shot inulin clearances on the days following dialysis. additionally hemolytical activity of complement was determined. inulin clearance on day was reduced significantly but there was no difference in the degree of decrement in glomular filtration rate (gfr) between dialyzed and undialyzed rats, nor between the dialyzed animals with different membranes (gfr: no hi): . _+ . ; cupro: . _+ . ; hemo: . _+ . ; an : . _+ . ). the evaluation of renal function by day nine revealed significant recovery for all airf-groups compared to day (p< . ), irrespective of wether they underwent dialysis or not, or the type of dialysis membrane. complement activation could be detected in all dialyzed groups but no statistical differences between the animal groups dialyzed with different membranes were noticed. our findings refute the hypothesis that in airf exposure to complement-activating cellulosic membranes impairs the recovery of renal function in rats. changes patients: patients who underwent first cadaver kidney transplantation in our unit between january and december in were involved. the recipients were divided into groups: group i." non functioning graft (n= ); group ii: delayed graft function (n= ), group ili: good graft function (n= ). the grouping criteria were: a/haemodialysis in the fii~t postoperative days, b/diuresis in the i st postoperative day, c,' scram crcatininc difference between the st postoperative day and the preoperative level. all of the parameters were involved into the exarainatio, which we measllre in our every, day practice. results: the preoperative haematocrit level differed significantly between group i. ( . ) and croup ii. and iii. ( . and . , p< . ). intmo! emtive significant differences were found between the different groups in systolic blood pressure (group i. hgrmn, group ii. hgnnn, group iii. hgmm, p< . ), mean arterial pressure (group i. hgmm, vs. group ii. hgnun p< . , vs. group iii. hgmm p< . ), and pulse-amplitude and rate-pressure product too. the second warm ishaemic time in group iii. was significantly shorter than in the other two groups (group iii. inin. vs. group ii. rain. p< . , vs. group i. rain. p< . !). the rejection rate was higher in the first days in the patients with non-functioning grafts (group i. % and group ii. % vs. group iii. %) . the other examined parameters have not differed significantly. conclusion: according to our results the success of the kidney transplantation is mnitifactorial. the most important factors of this relationship are: the perioperative fluid-balance, the maintenance of adequate perfusion blood pressure during the operation, good surgical technique and immunological problems.