key: cord- -mu u bvj authors: wiesen, jonathan; komara, john j; walker, esteban; wiedemann, herbert p; guzman, jorge a title: relative cost and outcomes in the intensive care unit of acute lung injury (ali) due to pandemic influenza compared with other etiologies: a single-center study date: - - journal: ann intensive care doi: . / - - - sha: doc_id: cord_uid: mu u bvj background: critical illness due to h n influenza has been characterized by respiratory complications, including acute lung injury (ali) or acute respiratory distress syndrome (ards), and associated with high mortality. we studied the severity, outcomes, and hospital charges of patients with ali/ards secondary to pandemic influenza a infection compared with ali and ards from other etiologies. methods: a retrospective review was conducted that included patients admitted to the cleveland clinic micu with ali/ards and confirmed influenza a infection, and all patients admitted with ali/ards from any other etiology from september to march . an itemized list of individual hospital charges was obtained for each patient from the hospital billing office and organized by billing code into a database. continuous data that were normally distributed are presented as the mean ± sd and were analyzed by the student’s t test. the chi-square and fisher exact tests were used to evaluate differences in proportions between patient subgroups. data that were not normally distributed were compared with the wilcoxon rank-sum test. results: forty-five patients were studied: in the h n group and in the noninfluenza group. mean ± sd age was similar ( ± and ± years, respectively, p = . ). h n patients had lower apache iii scores ( ± vs. ± , p = . ) and had higher pplat and peep on days , , and . hospital and icu length of stay and duration of mechanical ventilation were comparable. sofa scores over the first weeks in the icu indicate more severe organ failure in the noninfluenza group (p = . ). hospital mortality was significantly higher in the noninfluenza group ( vs. %, p = . ). the noninfluenza group tended to have higher overall charges, including significantly higher cost of blood products in the icu. conclusions: ali/ards secondary to pandemic influenza infection is associated with more severe respiratory compromise but has lower overall acuity and better survival rates than ali/ards due to other causes. higher absolute charges in the noninfluenza group are likely due to underlying comorbid medical conditions. the spread of a novel h n strain of the influenza a virus represents the first pandemic of the st century and the first influenza pandemic since [ ] . compared with seasonal influenza, this strain was more prevalent in younger-aged individuals, obese patients, and pregnant women [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . severe cases of pandemic h n resulted in respiratory failure thought to be secondary to direct cell damage and systemic cytokine release resulting in acute lung injury (ali) or acute respiratory distress syndrome (ards) requiring prolonged ventilatory assistance and the frequent use of rescue therapies [ , , , [ ] [ ] [ ] [ ] [ ] . limited data exist that compare the clinical differences between ali in h n patients and ali arising from other etiologies. furthermore, whereas a number of studies have assessed different aspects of the economic impact of the recent pandemic [ ] [ ] [ ] [ ] , few have focused on the health care cost of the pandemic, particularly the utilization of limited icu resources. we report the severity, clinical outcomes, and hospital charges of ali/ards secondary to pandemic influenza a infection compared with ali/ards from other etiologies during a similar period of time. based on clinical bedside observations and published reports [ , , ] , we hypothesize that ali/ards secondary to pandemic influenza is associated with similar icu outcomes but increased resource utilization and higher hospital charges due to the frequent need for rescue interventions and prolonged ventilatory assistance. the study was approved by the human investigation committee of the cleveland clinic foundation (ccf) (institutional review board approval # - ) as a retrospective, single-center study at the ccf medical icu. patients were identified from a unit-based acute lung injury screening database (cleveland clinic is one of the centers participating in the ardsnetwork) and the h n patient log maintained during the fall-winter season of - . patients were included if they met criteria for ali (pao /fio ≤ ; acute bilateral infiltrates; positive pressure ventilation via endotracheal tube; and no clinical evidence of left atrial hypertension or congestive heart failure) between the months of september to march -the time that influenza infection was most prevalent. diagnostic methods for influenza a virus detection consisted of rapid antigen testing, polymerase chain reaction (rtpcr), and viral culture from nasopharyngeal swabs, tracheal aspirates, and bronchioalveolar lavage specimens. the patients were grouped into two categories: those with laboratoryproven h n infection; and those in whom h n was not clinically suspected. only patients with confirmed infection were included in the influenza group to ensure that the clinical course of the disease was accurately captured. patients were excluded from the study if they did not meet the above criteria for ards, or if clinical suspicion pointed to a likely pandemic viral infection with negative diagnostics. a research electronic data capture (redcap) database was constructed with a complete listing of the patient's demographic and clinical information, including age, gender, height, weight, body mass index (bmi), presenting symptoms, past medical history, primary reason for admission to the icu, vital signs, presence of vasopressors, laboratory values, ventilator settings and respiratory parameters, acute physiology and chronic health evaluation (apache) iii and sequential organ failure assessment (sofa) scores on admission to the micu, number of intubated days, duration of icu and hospital stay, mortality, and rescue therapies (namely inhaled nitric oxide, proning, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation [ecmo]) [ ] . the data collection was de-identified and collected in accordance with hipaa guidelines. as part of the routine micu respiratory therapy protocol, mechanical ventilation parameters are recorded every hours. all patients are managed according to a mechanical ventilation protocol that incorporates the use of nonconventional modes when a lung protective strategy on conventional modes failed to provide adequate oxygenation. the following criteria were used to define the analyzed parameters: ) mode of ventilation: the mode of ventilation that was used for the longest time for a given day; ) pao /fio : worst daily ratios were recorded; ) plateau pressure (pplat): for patients on volume control ventilation the airway pressure was measured after a -second inspiratory hold without concomitant active inspiratory efforts, and for patients on pressure control ventilation (pcv) the highest total system pressure (peep + inspiratory pressure) was recorded; ) positive end expiratory pressure (peep): the value corresponding to the highest peep for the day was recorded; ) tidal volume (vt): the largest daily volume was recorded. respiratory data were captured on the first day of intubation (day ) and then on subsequent days , , and of mechanical ventilation. there were no differences in ventilator protocols or management between the two groups. an itemized bill of individual charges for each patient was obtained from the hospital billing office and was organized by billing code into the following categories: room/board, pharmacy, supplies, laboratory, radiology, surgical (including procedures performed under general anesthesia), blood products, respiratory services, dialysis, and miscellaneous (which included some professional fees, nonsurgical procedures and phlebotomy, and diagnostics not included in the other categories, such as electroencephalograms, electrocardiograms, echocardiograms, cardiac catheterizations, and vascular studies). the values represent the hospital charges for the aforementioned services rather than the actual reimbursement, which may be subject to more variability. the single-center nature of the study removes interfacility differences in clinical and billing practices. continuous data that were normally distributed are presented as the mean ± sd and were analyzed by the student's t test. the chi-square and fisher exact tests were used to evaluate differences in proportions between patient groups. in instances where the data were not normally distributed, the groups were compared with the wilcoxon rank-sum test. differences were considered statistically significant if the p value was < . . fifty-one patients were identified in the acute lung injury screening database between september and march . twenty-two met criteria for ali and did not have confirmed or suspected h n infection and were thus included in the noninfluenza group (ali/ards secondary to noninfluenza etiologies). thirty-six patients in the h n patient log had confirmed influenza a testing. of those, had ali requiring mechanical ventilation (mv) during their micu stay and were included in our analysis. demographics, presenting symptoms, past medical history, and acuity on admission are shown in table . patients in the influenza group tended to be younger with a higher bmi. patients in the influenza group presented more often with lower respiratory infection ( vs. %, p = . ) and had increased requirement for mechanical ventilation on admission to the icu ( vs. %, p = . ). on the other hand, the noninfluenza group had a higher propensity to present with shock requiring vasopressors ( vs. %, respectively, p = . ). the primary cause of ali in the h n group was pneumonia (n = ), whereas in the noninfluenza group the etiologies were more varied, including pneumonia (n = ), sepsis (n = ), aspiration of gastric contents (n = ), transfusion reaction (n = ), and other (n = ). whereas seven patients ( %) in the h n group were considered healthy, only one patient ( %) in the noninfluenza group had no comorbid medical conditions on admission to the icu (table ) . this difference is reflected in the lower mean apache iii score on admission to the icu in the h n group ( ± vs. ± , p = . ), despite similar sofa scores ( . ± . and . ± . , p = . ). there were no statistically significant differences between the two groups for initial laboratory data, including white blood cell count, platelets, serum creatinine, bilirubin, and creatinine kinase. the number of patients who developed acute renal failure that required dialysis throughout their icu stay was the same (n = ) in both groups. sofa scores on days , , , and of mechanical ventilation indicate that patients in the noninfluenza group had more severe organ failure during their icu stay (p = . ; table ). table shows oxygenation index and mechanical ventilation related parameters on days , , , and . there was a nonsignificant trend toward worsening hypoxia in the h n group, despite significantly higher peep and pplat on days , , and . tidal volumes were comparable throughout. plateau pressures in the h n group were high due to the relative decrease in pulmonary compliance in h n -related lung injury. four patients in both groups were ventilated with airway pressure release ventilation (aprv). more patients in the influenza group required rescue therapies on day of mechanical ventilation ( vs. , respectively, p = . ); however, similar numbers of patients in both groups required rescue therapies over the duration of mv ( and patients, respectively). rescue therapies in the h n group included inhaled no (n = ), ecmo (n = ), prone ventilation (n = ), and high-frequency ventilation (n = ), and in the noninfluenza group only inhaled no (n = ) and prone ventilation (n = ). mechanical ventilation days were comparable between groups ( ± vs. ± days for groups i and ii, respectively, p = . ) as were -day ventilator-free days ( ± . and . ± , p = . ). four patients in the h n group and seven in the noninfluenza group underwent a tracheostomy procedure. hospital and icu los were comparable (median ± iqr: ± vs. . ± . and ± vs. ± . days for the influenza group and ii, respectively, wilcoxon p = . and . ). mortality was significantly higher for patients in the noninfluenza group ( vs. %, p = . ). interestingly, a kaplan-meier curve of icu mortality (figure ) indicates that patients in the h n group were more likely to be discharged alive from the icu when the length of stay was greater than days, despite a trend toward higher mortality within the first weeks. even though all charges were higher in the noninfluenza group, only the difference in blood products utilized in the icu was significant ( ± vs. ± thousands of u.s. dollars, wilcoxon p < . ; table ). differences in icu charges in pharmacy (p = . ), supplies (p = . ), radiology (p = . ), and miscellaneous (p = . ) were large but not significant due to considerable variation. the proportion of charges in each of the major categories was similar between the groups (figure ). the average total icu cost per patient ( ± vs. ± thousands of u.s. dollars, wilcoxon p = . ) and the average icu cost per patient per day ( ± vs. ± thousands of u.s. dollars, wilcoxon p = . ) tended to be higher in the noninfluenza group. the fall of heralded the influx of patients suffering from severe hypoxic respiratory complications secondary to the pandemic h n influenza to icus across the country. due to the severity of pulmonary disease that many of these patients experienced, perception among treating clinicians was that these patients would have a all values expressed as mean ± sd. using mixed models, the overall p value comparing the influenza and noninfluenza groups is . . the trend over time was not significant (p = . ). worse outcomes and consume more resources, as measured by hospital charges, than patients who developed ali from other etiologies. we demonstrated that, contrary to what was perceived, pandemic influenza a ali/ ards was associated with a lower acuity and, consequently, lower hospital mortality that ali/ards from other etiologies, and had a similar icu and hospital los. icu and total hospital charges reflected a trend toward higher overall charges for room and board, blood products, pharmacy, and overall charge per patient in the noninfluenza group. in accordance with other descriptive reports of pandemic influenza [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , patients who tested positive for h n infection, tended to be young (no patients > years old), obese ( had bmi > kg/m ), and in relatively good health ( % with no comorbid medical conditions). there were no pregnant patients in either group. compared with other studies of pandemic influenza patients who required mechanical ventilation, sofa scores (mean . ) were similar, although apache ii ( ± ) scores were higher [ ] [ ] [ ] [ ] , , , ] . the degree of respiratory compromise in our patients was more severe than other reports judging by the higher peep requirements and longer duration of mechanical ventilation, which was roughly double that reported in other studies [ ] [ ] [ ] , , , , , ] . plateau pressures in these studies were not consistently reported. however, despite significantly longer ventilation duration and prolonged icu and hospital stays, the mortality in our cohort was not higher than that seen in other studies, which ranged from - % in patients who required mechanical ventilation [ ] [ ] [ ] , , , , , ] . looking at the different patient characteristics between groups, it may be tempting to postulate that the higher rate of patients with pulmonary ards in the h n group, in contrast to prevalent nonpulmonary ards in the noninfluenza group, would correlate with a higher peep response among the latter [ ] . our findings suggest the contrary. patients in the h n group had higher mean plateau pressure, likely indicative of lower compliance. the similarity of pao /fio ratios in the two groups may be a reflection of higher peep values used in the h n group for lung recruitment, rather than being indicative of comparable degrees of lung injury. although assessing recruitability from this retrospective analysis is difficult and may be inaccurate, the higher peep used and the implication of lower compliance observed are predictors of potentially recruitable lung [ ] . these observations support the recent call for a reevaluation of the ali and ards criteria to account for this heterogeneity in the patient population [ ] . a number of important differences between the two cohorts emerged as well. as expected, the noninfluenza group was older, had more comorbid medical conditions, and less often presented to the icu with respiratory failure. the degree of ventilator support was significantly higher in the h n group on days , , and , and there was a trend to more severe hypoxemia during that time as well. nevertheless, the use of use of aprv and rescue therapies was comparable in both groups. despite more severe respiratory compromise, h n patients did not have longer time on the ventilator, longer icu or hospital stays, or higher mortality. although sofa scores were similar, the noninfluenza group had significantly higher apache iii scores, likely secondary to points assigned to comorbid medical conditions. the high acuity of illness, as well as the presence of severe comorbidities, such as solid and hematologic oncologic conditions ( patients), chronic renal insufficiency ( patients), and cirrhosis of the liver ( patients), likely contributed to the poor outcomes in the noninfluenza group. conversely, despite more severe respiratory compromise, patients in the h n group were more likely to recover due to their younger age and better overall health histories. the % mortality in the noninfluenza group was much higher than typically reported in clinical trials, with one notable exception [ ] . however, reports from tertiary care centers involving patient cohorts with similar underlying comorbid conditions have reported equally high mortality rates [ ] . our observation brings up an interesting point, namely the difference between the reported mortality in clinical trials and the observed mortality in a similar clinical condition affecting patients that would have been excluded from such trials due to coexisting comorbidities. a kaplan-meier plot of icu mortality (figure ) indicates that although patients in the h n group were less likely to survive the first days of icu care, those that did survive past day were more likely to be discharged alive from the hospital. patients in the noninfluenza group were unlikely to survive if their icu length of stay exceeded weeks. ards is among the most expensive conditions encountered in the icu [ ] . in , bellamy and oye described the charges of patients with ards, with the most expensive being room and board ( %), clinical laboratory ( %), pharmacy ( %), and inhalation therapy and ventilation ( %) [ ] . twenty-five years later, our study indicates that the aforementioned categories continue to represent the most expensive charges incurred by ards patients in the icu. the overall similarity of charges in room and board and respiratory therapy between the two groups is likely indicative of the comparative durations of hospitalization and mechanical ventilation. interestingly, despite higher ventilatory requirements and more severe hypoxemia in the h n group, respiratory charges were similar between the two groups, suggesting that the high cost of maintaining a patient on mechanical ventilation is independent of the degree of ventilator support necessary. thus, respiratory charges are more likely a reflection of duration of mechanical ventilation rather than the degree of ventilator support necessary. absolute icu charges for room and board, blood products, pharmacy, radiology, average daily charge, and overall charge per patient were larger in the noninfluenza group. icu charges for blood products in the noninfluenza group were greater by a factor of four, and pharmacy charges double that of the h n group. this finding is likely a reflection of the higher prevalence of underlying comorbid medical conditions in the noninfluenza group, such as malignancy and cirrhosis, which require expensive medications and predispose to anemia. moreover, the high mortality in this cohort likely precluded even higher hospital charges. nevertheless, the h n cohort amassed charges of similar magnitude to the most ill and expensive patients in the icu, indicating the abundant health care resources consumed by severe pandemic influenza infection. there are a number of limitations to our study. as a retrospective chart review rather than a prospective investigation, the information was culled from sources that were at times incomplete. second, the study contained a relatively small number of patients, and measures taken to ensure internal validity of each group, such as limiting the influenza group to confirmed h n infection and the noninfluenza group to the duration of the influenza season, further limited its size. additionally, whereas our study provides descriptive information relevant to the patient population of our institution and tertiary referral centers with similar acuity, other icus may be exposed to a different cohort of patients. on the other hand, as a single-center study, potential differences in clinical and billing practices could be minimized. although a comprehensive charge profile of each patient was generated, trends in the timing of charges could not be obtained. finally, the hospital charge data were mined from an extensive database divided by charge coding, and therefore, some charges may have been mislabeled or inappropriately categorized. our study provides interesting observations about the clinical course, outcomes, and cost of the h n influenza pandemic. although patients with severe pulmonary complications of pandemic influenza infection have poor oxygenation and require significant ventilatory support and rescue therapies, their younger age and tendency to have fewer comorbid medical conditions contribute to their improved prognosis compared with patients with ali from other causes. both groups of patients consume enormous amounts of hospital resources, and physicians and policy makers must be aware of this when future pandemics arise. world now at the start of influenza pandemic california pandemic (h n ) working group: severe h n influenza in pregnant and postpartum women in california pediatric hospitalizations associated with pandemic influenza a (h n ) in argentina critical care services and h n influenza in australia and new zealand extracorporeal membrane oxygenation for influenza a(h n ) acute respiratory distress syndrome critically ill patients with influenza a(h n ) in mexico intensive care adult patients with severe respiratory failure caused by influenza a (h n )v in spain critically ill patients with influenza a(h n ) infection in canada pandemic (h n ) : epidemiological, clinical and prevention aspects hospitalized patients with h n influenza in the united states pandemic (h n ) influenza writing committee of the who consultation on clinical aspects of pandemic (h n ) influenza, bautista e, chotpitayasunondh t: clinical aspects of pandemic influenza a (h n ) virus infection clinical management of pandemic influenza a(h n ) infection h n : viral pneumonia as a cause of acute respiratory distress syndrome ventilator management for hypoxemic respiratory failure attributable to h n novel swine origin influenza virus hospitalized patients with h n influenza infection: the mayo clinic experience clinical findings and demographic factors associated with icu admission in utah due to novel influenza a(h n ) infection the macroeconomic impact of pandemic influenza: estimates from models of the united kingdom, france, belgium and the netherlands cost-effectiveness analysis of hospital infection control response to an epidemic respiratory virus threat economic consequences to society of pandemic h n influenza -preliminary results for sweden effectiveness and cost-effectiveness of vaccination against pandemic influenza (h n ) research electronic data capture (redcap)-a metadata-driven methodology and workflow process for providing translational research informatics support severe refractory hypoxaemia in h n ( ) intensive care patients: initial experience in an asian regional hospital lung recruitment in patients with the acute respiratory distress syndrome epidemiology and outcomes of acute lung injury effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome adult respiratory distress syndrome: hospital charges and outcome according to underlying disease variable costs of icu patients: a multicenter prospective study relative cost and outcomes in the intensive care unit of acute lung injury (ali) due to pandemic influenza compared with other etiologies: a single-center study the authors declare that they have no competing interests.authors' contributions jw and jk were responsible for the data input. jw and jg composed the manuscript. hw provided editorial assistance. ew provided the statistical analysis. all authors read and approved the final manuscript. submit your manuscript to a journal and benefi t from: convenient online submission rigorous peer review immediate publication on acceptance open access: articles freely available online high visibility within the fi eld retaining the copyright to your article submit your next manuscript at springeropen.com key: cord- -x ffw authors: damiani, elisa; carsetti, andrea; casarotta, erika; domizi, roberta; scorcella, claudia; adrario, erica; donati, abele title: comment on “respiratory mechanics and gas exchanges in the early course of covid- ards: a hypothesis-generating study” date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: x ffw nan we have read with great interest the article by diehl et al. on the evaluation of respiratory mechanics and gas exchanges in patients with acute respiratory distress syndrome (ards) due to covid- that was recently published in the annals of intensive care [ ] . in patients with moderate-to-severe ards, the authors observed high physiological dead space (v d /v t ) and ventilatory ratio (vr). several hypotheses are made to explain the pathogenesis of increased v d /v t , namely pulmonary embolism, alveolar overdistension, increased instrumental dead space, and diffuse microcirculatory dysfunction [ ] . even if alveolar overdistension due to high peepprotective ventilation, with regional compression of alveolar vessels, is likely to exert a major impact on lung mechanics in ards, the hypothesis of a contributing role of microvascular derangement is particularly captivating. lung injury in ards (and covid- pneumonia) seems mainly driven by a dysregulation of the reninangiotensin system, leading to increased vascular permeability, inflammation, pneumocyte apoptosis, and fibrosis [ ] . pulmonary microvascular injury, with leaky blood vessels, interstitial oedema, microthrombosis, and heterogeneous perfusion, may be the first responsible for ventilation/perfusion mismatch and increased dead space in ards. in patients with early moderate or severe ards, ospina-tascon et al. showed an inverse correlation between v d /v t and sublingual microcirculatory blood flow distribution [ ] . in their study, diehl et al. reported an elevation of markers of endothelial damage and thrombosis (i.e., circulating endothelial cells and d-dimers); however, they did not show any statistical correlation with variables of respiratory mechanics and/ or gas exchange [ ] . in a recent report, we described the sublingual microcirculation of mechanically ventilated patients with severe sars-cov- pneumonia and showed an inverse correlation between perfused vessel density (pvd) and d-dimers [ ] . this relationship was confirmed in sars-cov- patients on veno-venous extracorporeal membrane oxygenation [ ] . unfortunately, we could not evaluate the relationship with physiological dead space, because v d /v t data were not available for our cohort. we calculated the vr for patients who were not receiving extracorporeal membrane oxygenation (median vr = . [ . - . ]); however, we could not find any significant correlation with d-dimers (spearman's rho = − . , p = . ) or microcirculatory variables (spearman's rho for pvd = . , p = . ). the extremely low sample size significantly limits these analyses. this comment refers to the article available at https ://doi.org/ . /s - - - . taken together, all these data would suggest a connection between microvascular dysfunction, coagulopathy, and increased physiological dead space in the genesis of respiratory failure in covid- pneumonia. nonetheless, the cause-effect relationship remains to be proven. an altered sublingual microcirculation could just be an epiphenomenon of a hemodynamic compromise in patients with worse respiratory mechanics: in our cohort, sublingual microvascular perfusion tended to decrease with increasing driving pressures [ ] . further investigations are imperative to gain a more comprehensive understanding of the pathophysiology of covid- and select the best treatment strategy. appropriately designed clinical and laboratory-controlled studies are needed to prove any causal relationship between microvascular derangements and increased dead space ventilation. finally, a consideration must be made regarding the article by diehl et al. [ ] : the authors used side-stream capnography, which may be inaccurate for calculations of v d /v t as compared to main-stream capnography. the transport delay of the gas in the sampling tube with axial mixing of the gas residing in the tube, together with the variable sampling flow rate resulting from the alternating positive airway pressure during mechanical ventilation, leads to underestimation and distortion of the capnogram, with consequent inaccurate v d /v t calculations. respiratory mechanics and gas exchanges in the early course of covid- ards: a hypothesis-generating study angiotensin system and its opposing arm in sars-cov- related lung injury microcirculatory dysfunction and dead-space ventilation in early ards: a hypothesis-generating observational study microvascular alterations in patients with sars-cov- severe pneumonia sublingual microcirculation in patients with sars-cov- undergoing veno-venous extracorporeal membrane oxygenation publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. all authors equally contributed to the study's conceptualization, methodology, and analysis. ed, ac, ec wrote the manuscript. rd, cs, ea, and ad revised the manuscript critically. all authors read and approved the final manuscript. none. ethics approval and consent to participate not applicable. not applicable. the authors declare that they have no competing interests.received: july accepted: october key: cord- -e fbg i authors: liu, songqiao; zhao, zhanqi; tan, li; wang, lihui; möller, knut; frerichs, inéz; yu, tao; huang, yingzi; pan, chun; yang, yi; qiu, haibo title: optimal mean airway pressure during high-frequency oscillatory ventilation in an experimental model of acute respiratory distress syndrome: eit-based method date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: e fbg i background: high-frequency oscillatory ventilation (hfov) may theoretically provide lung protective ventilation. the negative clinical results may be due to inadequate mean airway pressure (mpaw) settings in hfov. our objective was to evaluate the air distribution, ventilatory and hemodynamic effects of individual mpaw titration during hfov in ards animal based on oxygenation and electrical impedance tomography (eit). methods: ards was introduced with repeated bronchoalveolar lavage followed by injurious mechanical ventilation in ten healthy male pigs ( . ± . kg). settings of hfov were hz (respiratory frequency), % (inspiratory time) and cmh( )o (∆pressure). after lung recruitment, the mpaw was reduced in steps of cmh( )o every min. hemodynamics and blood gases were obtained in each step. regional ventilation distribution was determined with eit. results: pao( )/fio( ) decreased significantly during the mpaw decremental phase (p < . ). lung overdistended regions decreased, while recruitable regions increased as mpaw decreased. the optimal mpaw with respect to pao( )/fio( ) was ( . – . ) cmh( )o, that is comparable to eit-based center of ventilation (eit-cov) and eit-collapse/over, . ( . – . ) and . ( . – . ), respectively (p = . ). eit-cov decreasing along with mpaw decrease revealed redistribution toward non-dependent regions. the individual mpaw titrated by eit-based indices improved regional ventilation distribution with respect to overdistension and collapse (p = . ). conclusion: our data suggested personalized optimal mpaw titration by eit-based indices improves regional ventilation distribution and lung homogeneity during high-frequency oscillatory ventilation. acute respiratory distress syndrome (ards) is common in icu characterized by diffuse endothelial and epithelial injury, inflammatory pulmonary edema, small lung, lung injury inhomogeneities and severe hypoxemia [ , ] . mechanical ventilation remains mainstay in the management of patients with ards [ ] . lung protective ventilation with low tidal volumes [ ] , positive end-expiratory pressure (peep) [ , ] and prone position [ ] may improve outcomes. nevertheless, the mortality of ards patients remains high, up to - % [ ] . high-frequency oscillatory ventilation (hfov) delivered high mean airway pressure (mpaw) and extremely small tidal volumes to prevent alveolar derecruitment/ overdistention as well as avoid the repeated opening/ closing of individual alveolar [ ] . clinical trials [ ] and large animal trials [ ] have demonstrated that hfov improves oxygenation, reduces lung inflammatory processes and histopathological damages, and attenuates oxidative lung injury compared with conventional mechanical ventilation (cmv). currently, clinical data do not support the use of hfov in patients of ards. two major multicenter, randomized trials (oscar and oscillate) failed to show improvement on -day mortality in moderate-to-severe ards patients [ ] [ ] [ ] . a meta-analysis found that hfov might not improve outcome compared with cmv [ ] . one possible reason may be the improper hfov protocols applied and inadequate hfov settings. the optimal mpaw titration is still a challenge during hfov. the selection of paw is usually guided by a static p-v curve or based on the oxygenation index [ ] ; however, either computed tomography scanning [ ] or frequent blood gas analysis is indispensable. recently, a study showed that hfov guided by transpulmonary pressure improved systemic hemodynamics, oxygenation, and lung overdistension compared with conventional hfov in animals [ ] . but the ventilation distribution and homogeneity remain unknown toward the methods mentioned above to titrate mpaw. electrical impedance tomography (eit) might allow the clinician to better adjust these ventilatory settings. eit is a bedside imaging technique that enables monitoring air distribution in the lungs [ ] . our previous study has showed the gi index may provide new insights into air distribution in cmv and may be used to guide ventilator settings [ , ] . eit might allow the clinician to better adjust ventilatory settings in hfov. it is possible that hfov would be safer and more effective with a more individualized approach to setting mpaw adjusted according to ventilation distribution bedside. in the present study, our objective was to evaluate the air distribution, ventilatory, and hemodynamic effects of individual mpaw titration in hfov based on oxygenation and eit. the study was approved by the science and technological committee and the animal use and care committee of the southeast university, school of medicine, nanjing, china. all animal procedures and protocols were performed according to the guidance for the care and use of laboratory animals [ ] . a total of ten healthy male pigs (body weight . ± . kg, mean ± sd) were included. pigs were anesthetized with an intramuscular injection of ketamine hydrochloride ( mg/kg), atropine ( mg/kg) and fentanyl citrate ( mg/kg), followed by a continuous intravenous infusion of propofol ( - mg/kg/h), fentanyl citrate ( . - . μg/kg/h), midazolam ( . mg/kg/h), and atracurium ( . mg/kg/h). after the induction of anesthesia, the pigs were placed in supine position, on a thermo-controlled operation table to maintain body temperature at about . ℃. with local anesthesia, a mid-line neck incision was performed and the trachea was secured using an -mm-id endotracheal tube. the animals received conventional mechanical ventilation (servo-i ventilator, solna, sweden) under volume-controlled mode (respiratory rate breaths per minute; inspiration-to-expiration time ratio : and peep cmh o; fraction of inspiration o (fio ) and tidal volume (v t ) . and ml/kg, respectively). a swan-ganz catheter (arrow international, reading, pa, usa) was inserted through the internal jugular vein to measure central venous pressure (cvp) and pulmonary arterial wedge pressure (pawp). a thermistor-tipped picco catheter (pulsion medical system, munich, germany) was advanced through the right femoral artery to monitor the mean arterial pressure (map) and cardiac output (co). in addition, arterial blood samples were collected from a picco catheter. a continuous infusion of a ml/(kg h) balanced electrolyte solution was administered during the experiment, and map was maintained above mmhg with rapid infusions of . % saline solution at up to ml/kg, if required. after the initial animal preparation, the pigs were stabilized for min and baseline measurements (t baseline ) were taken. ards was induced by repeated bilateral bronchoalveolar lavage with ml/kg of isotonic saline ( ℃). after stabilization, an arterial blood gas sample was obtained to verify that the ratio of partial pressure of arterial oxygen pao and fio decreased to less than mmhg, followed by h of injurious mechanical ventilation (peep cmh o and distending pressure cmh o in pcv). pao /fio remained less than mmhg for min (t ards ) with an increase of fio to . . the mechanical ventilation mode was then switched to hfov (fio . ; respiratory frequency hz; inspiratory time %; ∆pressure cmh o), and a recruitment maneuver was performed (mpaw of cmh o for s) after -min hfov ventilation. after recruitment, stepwise mpaw decrements were performed from to cmh o with a step of cmh o decrease every min. (flowchart of the study is showed in additional file : figure s ). cvp, pawp, map and co were recorded at every pressure level. all blood gas measurements were performed using an automated blood gas analyzer (nova m; nova biomedical, waltham, ma, usa). continuous eit measurements started after tracheostomy (pulmovista , dräger medical, lübeck, germany). an eit electrode belt with electrodes was placed around the thorax cm above the xyphoid level and one reference ecg electrode was placed at the abdomen. the frequency of injected alternating current was selected automatically according to the noise spectrum. the images were continuously recorded and reconstructed at hz. the eit data were reconstructed using a finite element method-based linearized newton-raphson reconstruction algorithm [ ] . baseline of the images was referred to the lowest impedance value measured during t ards . oscillatory impedance variations of every s were averaged to present the ventilation distribution. one-minute period at the end of each mpaw step was used for further eit analysis. optimal mpaw with respect to oxygenation was defined as mpaw in the step before the one at which pao dropped by > % compared to previous step (additional file : figure s ). the center of ventilation (cov) index showing the vertical distribution of ventilation was calculated [ , ] : i i denotes impedance value of pixel i. y i is the pixel height and pixel i is scaled so the most ventral row is and the most dorsal row is . optimal mpaw with respect to eit-cov was defined as mpaw associated with the cov values closest to %. eit-based cov index higher than % at high mpaw steps indicated ventilation distribution toward gravity-dependent regions. recruitable regions compared to the highest mpaw level and overdistended regions were calculated using a method that was published recently [ ] . during the analysis of hfov in the present study, the oscillatory impedance variation was too small to confirm overdistension. therefore, compared to the original method, the volume changes induced by mpaw changes were used. the differences of impedance between lower mpaw and higher mpaw were calculated. the regions with less than % changes were denoted as regions with limited volume changes. these regions with almost no pixels changes were considered to be overinflated, if they belonged to those image pixels that were showed in lung regions at lower mpaw step. regions were considered to be recruitable if they were included in the lung regions at end-expiration at the highest mpaw step but not at the current mpaw step. the lung regions at mpaw level n were defined as pixels with higher impedance value (i) than % of maximum changes compared to the lowest mpaw level r (reference level, the lowest mpaw level). subsequently, the maximum differences of impedance (i max-diff ) between lower mpaw (denoted as mpaw level n) and higher mpaw (mpaw level n + ) were calculated. the regions with less than % changes were denoted as regions with limited volume changes (for pixel k, k ∈ i, i k < % × i max-diff ). these regions k were compared to lung regions at mpaw level n (j n ). they were considered to be overinflated, if they belonged to lung regions at mpaw step n at the same time (k ∩ j n intersection of set k and set j n ). the numbers of pixels in these two regions were plotted against decremental mpaw. optimal mpaw with respect to recruitable and overdistended regions was defined as the step where these two-pixel curves intersected. if the curves not intersected, mpaw with the lowest sum of recruitable and overdistended regions was selected. with the nature of this method, no values could be calculated for the lowest mpaw step, since the calculation required a comparison with a lower mpaw step (eq. ). overdistension/recruitment ratio was defined as number of pixels in the overdistended regions over that in the recruitable regions. statistical analysis was performed with the mat-lab software package (matlab . statistic toolbox, the mathworks inc., natick, ma, usa). due to the limited number of subjects, results are presented as median ± interquartile range. one-way kruskal-wallis test was used to assess the significance of differences in hemodynamics and oxygenation among different mpaw, and differences in optimal mpaw estimated with various criteria. a p value lower than . was considered statistically significant. wilcoxon signed-rank test was applied for further comparison within groups and the significance levels were corrected for multiple comparisons using holm's sequential bonferroni method. ards was successfully induced by repeated bronchoalveolar lavages in all pigs. the induction of ards led to a significant decrease in pao /fio (p < . ). map and co increased while cvp and pawp decreased along with the decremental mpaw trial. hemodynamic data during the mpaw trial are plotted in additional file : table s . the effect of mpaw on the pao /fio and partial pressure of arterial carbon dioxide (paco ) during hfov are shown in additional file : figure s . during the decremental phase, significant decrease in pao /fio and increase in paco were found between the mpaw step of cmh o and cmh o (p < . ) (additional file : figure s left). the optimal mpaw calculated by individual animal with respect to pao /fio was ( . - . ) cmh o. cov decreased along with mpaw decrease revealing a redistribution of ventilation toward non-dependent regions (fig. , left) . the optimal mpaw with respect to eit-cov in all pigs was . ( . - . ) cmh o and the values among individuals varied a lot. eit-derived overdistended regions decreased as mpaw decreased (fig. , right, green circles) . at the same time, recruitable regions increased (black stars). the optimal mpaw using the approach based on the calculated eitcollapse/over was . ( . - . ) cmh o. the optimal mpaw with respect to pao /fio was ( . - . ) cmh o, that is comparable to eit-based center of ventilation (eit-cov) and eit-collapse/ over, . ( . - . ) and . ( . - . ), respectively (p = . ). the differences between the selected mpaw according to oxygenation and according to "eit-cov" and "eit-collapse/over" were compared with bland-altman plots (fig. ) . the differences in mpaw selection between oxygenation and eit-based methods could be as high as cmh o in some pigs. the optimal mpaw settings derived from oxygenation, eit-cov and eit-collapse/ over were compared (table ). in fig. , overdistended and recruitable regions at mpaw levels selected based on oxygenation were illustrated. in each pig, the optimal mpaw defined with oxygenation was given (x-axis). the mpaw titrated by eit-based indices improved regional air distribution with respect to overdistension and collapse (comparison among mpaw titration strategies, p = . ) ( table ) . in the present study, novel eit-based method titrating mpaw under hfov was proposed and evaluated in ards model. the titration results were compared with oxygenation method and the effects on lung homogeneity were examined. we found that the individual mpaw titrated by eit-based indices improved regional ventilation distribution with respect to overdistension and collapse and the suggested mpaw may not always match the ones proposed by oxygenation method. hfov may remain a tool in managing patients with severe ards and refractory hypoxemia and not the firstline treatment for ards patient. hfov with high mpaw values applied in both two trials [ , ] might contribute to negative clinical outcome on ards patients and canceled out the positive effects. hfov using paw set according to a static p-v curve [ ] , oxygenation, mean airway pressure during cmv [ ] , and transpulmonary pressure [ ] has been examined in clinical and animal studies, but the bedside monitoring base on ventilation distribution is lacking. in the present study, we provide new mpaw titration method in respect of regional ventilation distribution that improves lung homogeneity. the increased mpaw lead to more lung tissue hyperinflated, and the eit-cov decrease, which revealed redistribution toward non-dependent regions. a critical issue of this eit-based method was the pre-defined threshold used to identify lung regions. further studies are required to confirm if the threshold used in the present study is optimal for various subjects and conditions. the reliability of eit has been confirmed and eit has been used in clinic setting and adjust of cmv. eit has been used in peep titration and tidal volume setting by comparison with various conventional methods, such as ct [ ] , single-photon-emission computed tomography [ ] , positron emission tomography [ ] , and pneumotachography [ ] . previous studies have already shown that eit was able to monitor ventilation distribution during hfov in preterm infants and patients with chronic obstructive pulmonary disease [ , ] . the optimal settings based on oxygenation were comparable to eit-cov and eit-regional ventilation distribution. it was also observed that overdistended regions were large at the mpaw selected with oxygenation method in several pigs. pf ratio is an invasive method with a certain time delay in response to pressure changes. although the average values between eit-derived measures were not very different, individual differences could be large (up to cmh o, figs. and ) . hence, mpaw titration with eit-based indices improved regional ventilation distribution while titration aiming oxygenation was not always the case. besides, it is worth to note that eit is currently the only bedside non-invasive tool to assess overdistension. further investigation should be conducted in future clinical studies. number of pixels is presented as black asterisk (recruitable lung region) and red circles (overdistended lung region) with the optimal mpaw were defined with oxygenation (upper). the number of pixels is presented as black crosses (recruitable lung region) and red squares (overdistended lung region) with the optimal mpaw were defined with eit-based center of ventilation index (lower x-axis) as well (lower) our study has some limitations. first, as an experimental study, these data were obtained in animals and its clinical impact may be limited. therefore, the optimal mpaw selected in the present study might be not suitable with that in ards patients. second, hfov should not be employed in the absence of well-trained expertise because of its complexity. further validation study to assess the feasibility of such strategies in ards patients with proposed method should be conducted. our data provide personalized optimal mpaw titration in hfov with eit-based indices, which may provide a new insight of regional ventilation distribution and lung homogeneity during high-frequency oscillatory ventilation. acute respiratory distress in adults acute respiratory distress syndrome: the berlin definition acute respiratory distress syndrome ventilation with lower tidal volumes as compared with traditional tidal volumes for acute 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validation study on electrical impedance tomography changes in lung volume and ventilation during surfactant treatment in ventilated preterm infants publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. supplementary information accompanies this paper at https ://doi. org/ . /s - - -z.additional file : figure s . flowchart of the study. figure s . pao /fio (left) and paco (right) during mpaw decrements trial after having fully recruited the lungs.additional file : table s . hemodynamics characteristics during decremental hfov mpaw (n = ). the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. the study had the approval of the science and technological committee and the animal use and care committee of the southeast university, school of medicine, nanjing, china. the animals were handled according to the helsinki convention for the use and care of animals. all authors have read this paper and agreed with the submission. inez frerichs has received reimbursement of travel, meeting expenses and speaking fees from swisstom and dräger, respectively. zhanqi zhao receives a consulting fee from dräger medical. the remaining authors have disclosed that they do not have any potential conflicts of interest. the authors state that neither the study design, the results, the interpretation of the findings nor any other subject discussed in the submitted manuscript was dependent on support. key: cord- -h d v ga authors: ospina-tascón, gustavo a.; bautista, diego f.; madriñán, humberto j.; valencia, juan d.; bermúdez, william f.; quiñones, edgardo; calderón-tapia, luis eduardo; hernandez, glenn; bruhn, alejandro; de backer, daniel title: microcirculatory dysfunction and dead-space ventilation in early ards: a hypothesis-generating observational study date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: h d v ga background: ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ards). although increased dead-space ventilation (v(d)/v(t)) has been described in ards, its mechanism is not clearly understood. we sought to evaluate the relationships between dynamic variations in v(d)/v(t) and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in v(d)/v(t) fraction during early stages of ards. methods: forty-two consecutive patients with early moderate and severe ards were included. peep was set targeting the best respiratory-system compliance after a peep-decremental recruitment maneuver. after min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. v(d)/v(t) was calculated from the co( ) production ([formula: see text] ) and co( ) exhaled fraction ([formula: see text] ) measurements by volumetric capnography. sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. all measurements were repeated h after. results: percentage of small vessels perfused (ppv) and microcirculatory flow index (mfi) were inverse and significantly related to v(d)/v(t) at baseline (spearman’s rho = − . and − . , p < . ; r( ) = . , and . , p < . , respectively) and h after (spearman’s rho = − . , and − . ; p < . ; r( ) = . and . , p < . , respectively). other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with v(d)/v(t). variations in ppv between baseline and h were inverse and significantly related to simultaneous changes in v(d)/v(t) (spearman’s rho = − . , p < . ; r( ) = . , p < . ). conclusion: increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in v(d)/v(t), while respiratory mechanics and oxygenation parameters do not. whether there is a cause–effect relationship between microcirculatory dysfunction and dead-space ventilation in ards should be addressed in future research. epithelial permeability, with subsequent loss of aerated lung tissue and increased lung stiffness [ ] . these alterations lead to imbalances between ventilation and perfusion relationships, which finally result in hypoxemia and impaired carbon dioxide clearance. an optimal ventilation-to-perfusion (v a /q) ratio ( . < v a /q < ) is necessary to ensure a normal gas exchange [ ] [ ] [ ] . typically, it has been considered that pulmonary perfusion in ards occurs in non-ventilated (v a /q < . ) or poorly ventilated ( . < v a /q < . ) lung units, which, in turn, results in vasoconstriction of perfusing arterioles [ ] . such v a /q mismatch in some lung regions in which perfusion largely exceeds ventilation, account for hypoxemia, which is the clinical hallmark of ards [ , , ] . nevertheless, distribution of ventilation to poorly perfused ( < v a /q < ), severely hypoperfused (v a /q > ) or non-perfused (v a /q ~ ∞) lung units might also occur in patients with ards [ ] and indeed, increases in v d /v t have been strongly related with adverse clinical outcomes [ ] [ ] [ ] . importantly, high v a /q and v a /q ~ ∞ ratios corresponding to lung regions where ventilation largely exceeds perfusion, account for carbon dioxide retention [ ] . increases in high v a /q and/or dead-space lung units have been classically attributed to alveolar overdistention with the subsequent compression of intra-alveolar vessels in the non-dependent lung areas [ , ] . nevertheless, increased dead-space ventilation has also been described in patients subjected to protective ventilation strategies with low plateau pressures [ , ] , which suggest that mechanisms different to alveolar overdistention should be implied. in normal conditions, the heterogeneity of systemic microcirculatory blood flow distribution is negligible [ ] . nevertheless, severe inflammation can induce microcirculatory alterations [ , ] determining alterations in oxygen extraction capabilities by the tissues and contributing to the development of multiple organ dysfunction [ ] . although there are many technical limitations to directly evaluate pulmonary microcirculation [ ] , heterogeneity of microvascular blood flow at pulmonary level could contribute to imbalances between ventilation and perfusion relationships. thus, considering microcirculatory dysfunction during inflammatory conditions as a generalized phenomenon, which may involve systemic and pulmonary vascular beds, we hypothesized that alterations in microvascular blood flow distribution evaluated at the sublingual mucosa as representative of an extra-pulmonary territory could be related to variations in dead-space ventilation v d /v t during early phases of moderate and severe ards. this prospective observational study was conducted in a -bed mixed icu from a university hospital. the local ethical and biomedical research committee approved the study (fundación valle del lili ebrc protocol number: ; approval number: - , ). a written informed consent was waived as no invasive procedures or new interventions were used. we daily screened all patients under mechanical ventilation in the icu during a -month period, searching for those with moderate and severe ards. to avoid the selection of cases with transitory hypoxemia simulating ards, patients were enrolled only after successfully completing a two-step selection process [ , ] : (a) first, patients mechanically ventilated through an endotracheal tube with a peep ≥ and fio ≥ . for at least h and meeting the moderate and severe ards criteria according to berlin consensus definitions [ ] were declared potentially eligible; (b) then, potential candidates were subjected to a fio trial at . while maintaining peep ≥ (to sustain a spo ≥ %, but ensuring peak inspiratory and plateau pressures < and cmh o, respectively) for at least min, after which, new arterial blood gases were collected. those patients maintaining a pao /fio ≤ after such peep/ fio trial and with < h of evolution of ards were finally included. the exclusion criteria were: < years of age, pregnancy state, history of neuromuscular diseases, moderate and severe copd (defined as fev < % predicted); history of intubation due to copd exacerbation, receiving domiciliary oxygen or long-term use of steroids because copd; history of congestive heart failure or any acute ischemic cardiac condition. a patient was also excluded when limitation of therapeutic effort orders were given. after fulfilling the two-step selection process, patients selected were connected to a mainstream co sensor and this in turn to a volumetric capnography module (infinity etco + respiratory mechanics module, dräger medical systems, telford, usa). mechanical ventilation parameters were adjusted after a stepwise alveolar recruitment maneuver, as it will be detailed later. after a min of stabilization period, we started capnography measurements while sublingual microcirculatory images were simultaneously acquired, such as detailed thereafter. a new set of measurements was obtained h after. arterial and mixed venous blood samples (when available) were drawn for gases analysis (abl , radiometer; copenhagen, denmark) at t and h after (t ). in all the cases, the attending physicians decided on the type of hemodynamic monitoring to use. complete respiratory and hemodynamic parameters were also registered simultaneously. at the time in which this study was performed, the local protocol included an initial recruitment maneuver to adjust peep in patients with severe ards. thus, patients were subjected to a stepwise recruitment maneuver with progressive peep increases until a peak pressure of cmh o while maintaining a driving pressure of cmh o, as described elsewhere [ , ] . once obtained the maximal peak pressure, it was sustained during min whereupon a decremental peep titration trial was conducted in steps of cmh o at min interval from to cmh o registering the corresponding compliance of the respiratory system (c rs ). after such a peep titration, a new alveolar recruitment was performed until a peak pressure of cmh o while maintaining a driving pressure of cmh o during min, to finally adjust the definitive ventilatory settings. definitive peep was set at the corresponding best c rs plus cmh o. if falls in c rs were observed in two consecutive downsteps, then the peep level was set at the highest compliance plus cmh o. according to the local protocol, the recruitment maneuver was stopped if one or more of following signs were observed: heart rate > or < bpm; decrease of mean arterial pressure < mmhg or systolic pressure < mmhg; acute atrial fibrillation, atrial flutter or ventricular tachycardia. thereafter, mechanical ventilation was set in volumecontrolled mode or in pressure-controlled, according to the selection of the attending physician. in the first case, ventilation was set at vt of ml/kg of predicted body weight maintaining plateau pressures < cmh o, flow of l/min, inspiratory pause of . s, i:e ratio of : to : , respiratory rate to match the minute ventilation previous to the recruitment maneuver, fio necessary for spo ≥ and ≤ % and peep adjusted as indicated above. if plateau pressures were > cmh o, then vt was reduced to a minimum of ml/kg of predicted body weight. for those ventilated in pressure-controlled mode, driving pressure was adjusted to maintain vt ml/kg of predicted body weight (or less if vt/c rs > ), i:e ratio : to : , minute ventilation matching that previous to the recruitment maneuver, peak inspiratory pressure ≤ cmh o, and fio and peep adjusted as indicated above. after an automatic purge and calibration procedure, a mainstream co sensor was placed between the ventilator circuit and the patient connection. this sensor was in turn connected to a volumetric capnography module (infinity etco + respiratory mechanics module, dräger medical systems, telford, usa). after selection of the ventilator settings, a min of stabilization period was allowed before to start the measurements. data trend for co production ( v co ) and exhaled minute ventilation (v e ) were averaged over min. v co measurements were obtained at standard temperature and pressure, and dry (stpd), whereby a correction factor of . mmhg l/ml was used to convert to body temperature, and pressure, saturated (btps). the fraction of exhaled co ( f eco ) was calculated dividing the v co by the v e (eq. ): exhaled co pressure ( p eco ) was then calculated as the product between the f eco and the barometric pressure minus the water vapor pressure (eq. ): where p b corresponds to the local barometric pressure (i.e., mmhg). subsequently, v d /v t was calculated by the enghoff modification of the bohr equation (eq. ): all measurements of v co performed by the module were automatically corrected for circuit compression, as described elsewhere [ ] . a sidestream dark-field (sdf) imaging device (micro scan; microvision medical, amsterdam, the netherlands) was used to explore the sublingual microcirculation simultaneously to dead-space fraction measurements, ventilatory mechanics and oxygenation parameters at both inclusion and h after. a cutoff value of μm was used to classify vessels as large or small. continuous flows were considered as normal while intermittent and stopped flows were considered as abnormal. according to the consensus for the evaluation of microcirculation, we calculated the proportion of small vessels perfused (ppv), the total vascular density (tcd) and the functional capillary density (fcd) [ ] . a heterogeneity index of microcirculatory blood flow was also calculated as the difference between maximal and minimal ppv values in five different mucosa areas divided by its own mean value (see additional file ). additionally, we reported the microvascular flow index (mfi). a detailed description about microcirculatory blood flow assessment is provided in additional file . ( ) sample size calculation is described in additional file . distribution of data was tested using the kolmogorov-smirnov test. non-parametric test for related samples were used to evaluate the differences on hemodynamic, respiratory, capnometry and microcirculatory blood flow parameters between baseline and h after. the relationships between the v d /v t , percentage of small vessels perfused (ppv), and microcirculatory blood flow index (mfi) were evaluated by the spearman rho test. other bivariate correlations between v d /v t , pao /fio , and respiratory mechanics were also performed using spearman rho test. additionally, simple linear regression models with linear and quadratic terms and their respective coefficients of determination (r ) were used to evaluate the relationship between each microcirculatory, respiratory mechanics or oxygenation parameter and the v d /v t at both baseline and h after. finally, we calculated the delta of variation of v d /v t and ppv measurements between baseline and h after. then, a spearman rho was used to evaluate the correlation between v d /v t and ppv dynamic variations from baseline to day- . furthermore, a simple linear regression model with quadratic term and its respective coefficient of determination (r ) was used to evaluate the relationship between variations in ppv and v d /v t from baseline to h after. data are presented as median [percentiles - ]. a p value ≤ . ( -tailed) was considered significant. a total of patients with moderate and severe ards were included in the study. a complete flowchart detailing the selection process is shown in additional file : figure s , while a strobe statement checklist for observational studies is provided in additional file : table s . mortality at day- and day- were % and . %, respectively. the icu length of stay was . [ . - . ] days. general characteristics are presented in table , while hemodynamics, respiratory mechanics, blood gases analysis, pulmonary dead-space fraction and microcirculatory blood flow parameters at baseline and h after are presented in table . we observed an inverse and significant relationship between ppv and v d /v t at both baseline (spearman rho = − . , p < . ; r = . , p < . ) and h after (spearman rho = − . , p < . ; r = . , p < . ) (fig. a, b) . similar findings were observed between v d /v t and the microcirculatory flow index at baseline (spearman rho = − . , p < . ; r = . , p < . ) and h after (spearman rho = − . , p < . ; r = . , p < . ) (fig. c, d) . there were no significant correlations between v d /v t and other respiratory mechanics and oxygenation parameters (fig. , additional file : table s ) . a significant relationship was observed between the variation in v d /v t and the percentage of variation of ppv from baseline measurements to h after (spearman rho = − . , p < . ; r = . , p < . ) (fig. , additional file : figure s ). additional information about survivors and non-survivors at day- is provided in additional file : table s . after simultaneous calculation of dead-space fraction by volumetric capnography and exploration of sublingual microcirculation by the sdf technique during the early stages of moderate and severe ards, we retrieved two hypothesis-generating observations: (a) v d /v t is inverse and significantly related with sublingual microcirculatory blood flow distribution, while peep levels, respiratory airway pressures, pao /fio and lung strain surrogates : (v t /c rs ) do not; (b) v d /v t variations were closely related with dynamic changes in the microcirculatory blood flow distribution observed at sublingual mucosa. other mechanisms unrelated to shunt-induced hypoxemia could be implicated in gas exchange abnormalities and in the onset of pulmonary and extra-pulmonary multiorgan dysfunction in ards. distribution of ventilation to poorly perfused ( < v a /q < ), severely hypoperfused (v a /q > ) or non-perfused, i.e., true dead-space ventilation (v a /q ~ ∞) lung units, can also contribute to gas exchange disturbances and it might be a key piece in the pathophysiology of ards. some studies in the past demonstrated the occurrence of increased pulmonary dead-space fraction in patients with acute hypoxemic respiratory failure [ , , ] , and highlighted the apparent relationship between high v d /v t and increased mortality [ ] . nevertheless, early studies included patients under non-lung-protective ventilation strategies, in which overinflation leading to capillary collapse could explain v a /q mismatching with the resultant increased v d /v t [ ] . remarkably, later studies in ards patients subjected to lung-protective ventilation, also demonstrated the occurrence of increases in v d /v t and confirmed its consistent relationship with worse clinical outcomes [ , , ] . in agreement with this, we observed increases in v d /v t at baseline and h after in patients with moderate and severe ards. importantly, we did not find any relationship between v d /v t and variables suggesting vascular collapse related to alveolar overdistention or increased pulmonary strain (e.g., v t /c rs ), although admittedly, fig. relationships between pulmonary dead-space fraction (v d /v t ) and the microcirculatory blood flow at baseline and h after. a scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and the proportion of small vessels perfused at baseline. b scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and the proportion of small vessels perfused h after. c scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and mfi at baseline. d scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and mfi h after. ppv: percentage of small vessels perfused; v d /v t : pulmonary dead-space fraction; hi: heterogeneity index of microcirculatory blood flow; mfi: microcirculatory blood flow index controlling airway pressures and v t /c rs (driving pressure) could not prevent alveolar overdistention because the inhomogeneous lung compromise in ards [ ] . relationships between microvascular blood flow and v d /v t have not been widely studied because of technical limitations to directly evaluate pulmonary microcirculation [ ] . our data suggest an apparent relationship between microcirculatory dysfunction and dead-space ventilation. admittedly, sublingual mucosa and pulmonary circulation are two dissimilar vascular beds with particular regulating mechanisms. nevertheless, during inflammatory conditions, microcirculatory dysfunction is a generalized phenomenon involving simultaneously most vascular beds [ ] , although with different effects depending on the territory studied [ ] . microcirculatory alterations have been described in autopsies and biopsies from lungs of patients with acute hypoxemic respiratory failure [ , ] and angiograms performed through pulmonary artery catheters demonstrated filling defects attributable to macro-and micro-emboli [ , ] . increases in v d /v t in our patients were well correlated with alterations in microcirculatory blood flow distribution detected in a non-pulmonary vascular bed. such observation could pose the hypothesis about heterogeneity of microvascular blood flow contributing to inequalities in v a /q relationships. indeed, variations of v d /v t from baseline to h after were closely related with dynamic changes in microcirculatory blood flow distribution at sublingual mucosa, which reinforce the strength of such relation. nevertheless, whether pulmonary microvascular alterations or other organ-specific microvascular blood flow can be evaluated or estimated through evaluation of an extra-pulmonary microvascular bed can result highly controversial [ ] . in normal conditions, heterogeneity of microvascular blood flow is negligible [ ] and matching of perfusion to metabolism usually improves during hypoxic or low-flow states [ ] . however, during inflammatory conditions, heterogeneity of microcirculation increases as consequence of the interruption of blood flow of individual capillaries causing derangements in the oxygen extraction capabilities, thus contributing to organ failure. in agreement with this, we observed important microcirculatory alterations consisting in decreased ppv, reduced fcd and increased heterogeneity of blood flow, which were in turn linked to more severe extra-pulmonary organ dysfunction quantified by sofa score (see additional file : table s ). pathophysiological mechanisms increasing v d /v t in ards are quite complex. an increased v d /v t reflects a global assessment of abnormal gas exchange, but not simply the contribution of discrete high v a /q regions and true anatomic dead space (v a /q ~ ∞). although the patchy pattern of vascular damage is a phenomenon clearly recognized in ards [ ] , no studies demonstrated that damaged areas necessarily receive substantial ventilation, as would be necessary to explain regions of high v a /q ratio. using the multiple inert gas elimination technique (miget) to evaluate the fractional contribution of each v a /q abnormality (shunt, mid-range v a /q heterogeneity, high v a /q, and anatomic dead space) on total v d /v t at progressively high peep levels, coffey et al. [ ] demonstrated similar v d /v t values at different peep levels mediated by very different physiologic abnormalities, although certainly, higher peep values were consistently related to high v a /q peaks. our results might add more complexity to the pathophysiology on increased v d /v t in ards suggesting the contribution of altered microcirculatory blood flow distribution on the increase of high v a /q units. routine assessment of pulmonary gas exchange in ards is based on analysis of oxygen and carbon dioxide partial pressures. these variables, although sensitive to intrapulmonary factors (e.g., shunt and v a /q matching), could be also altered by extra-pulmonary elements such as cardiac output, oxygen consumption, minute ventilation and inspired oxygen fraction. v d /v t values can widely vary according to the method used to estimate it [ ] . previous studies used the enghoff modification of the bohr equation (vd enghoff ) in patients with ards [ ] [ ] [ ] ] . nevertheless, this method could overestimate the real v d /v t when anatomic or intrapulmonary shunts are present as it assumes a perfect v a /q matching throughout all alveolar-capillary units [ , ] . (see figure on next page.) fig. relationships between pulmonary dead-space fraction (v d /v t ) and some respiratory mechanics and oxygen parameters at baseline and h after. a scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and the pao /fio ratio at baseline. b scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and the pao /fio ratio h after. c scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and peep levels at baseline. d scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and peep levels h after. e scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and the v t /c rs at baseline. f scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and the v t /c rs h after. g scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and pm aw at baseline. h scatter plot depicting the correlation between pulmonary dead-space fraction (v d /v t ) and pm aw h after. pao /fio ratio: arterial oxygen partial pressure to oxygen inspiratory fraction; peep: positive end-expiratory pressure; v t /c rs : tidal volume-to-respiratory system compliance ratio (i.e., driving pressure); pm aw : mean pressure of the airway ospina-tascón et al. ann. intensive care ( ) : although we used the vd enghoff method, we computed v d /v t from the co production ( v co ) and co exhaled fraction ( f eco ) measurements by volumetric capnography, which can accurately reflect measurements by metabolic monitors [ ] . trying to exclude cases with transitory hypoxemia simulating ards, we completed a two-step selection previously described [ , ] . although breathing pure oxygen may influence the v a /q distribution [ ] , our definitive v d /v t measurements were performed min after return to the previous fio , thus causing the lowest impact on v a /q balance. also, we used a stepwise recruitment maneuver with progressive peep increases, which was part of the local protocol at the time in which patients were included. probably at present, such maneuver would not be used as recent evidence suggests that it can be harmful [ ] . nevertheless, such maneuver allowed us to standardize the selection of peep and ventilatory parameters. we recognize that our study has important limitations. first, many hemodynamic and respiratory coexisting factors can influence v d /v t measurements. indeed, combination of hypovolemia, vasoactive agents and/or inotropics, cardiac output variations, pulmonary resistances and flows, distribution of ventilation along the lungs and even local microthrombi formation, might influence v d /v t variations in one or other direction. thereby, identical v d /v t elevations might reflect simultaneous alterations in diverse physiological components. second, our study is not able to demonstrate a causal association between v d /v t and sublingual microcirculation and it was not registered as observational study. nevertheless, dynamic variations from baseline to h after merit exploration in future studies. third, whether pulmonary microvascular alterations occur in parallel to other extra-pulmonary microvascular beds is highly controversial. however, microcirculation studies reveal simultaneous alterations at different beds during shock or inflammatory conditions. fourth, the number of cases included in our study was relatively small. however, the fact that our patients were strictly selected and calculation of v d /v t used v co and exhaled fraction of co ( f eco ) measurements by volumetric capnography strengthens our results. increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in v d /v t independently of respiratory mechanics and oxygen parameters, thus suggesting that microcirculatory alterations could be implicated in ventilation/ perfusion mismatching during early ards. the inverse dynamic relationships observed between sublingual microcirculation and dead-space ventilation poses a hypothetical pathophysiological mechanism during moderate and severe ards that deserves future research efforts. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . abbreviations ards: acute respiratory distress syndrome; co : carbon dioxide; copd: chronic obstructive pulmonary disease; c rs : compliance of the respiratory system; etco : end-tidal co ; fcd: functional capillary density; f eco : exhaled co fraction; mfi: microcirculatory flow index; p aco : arterial co partial pressure; p eco : exhaled co pressure; peep: positive end-expiratory pressure; ppv: percentage of small-vessels perfused; tcd: total capillary density; v a /q: ventilation-to-perfusion ratio; v co : co production; v d /v t : dead-space ventilation fraction; v e : exhaled minute ventilation; v t : tidal volume; v t /v rs : driving pressure. 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measurements by metabolic analyzer and volumetric co monitor how to evaluate the microcirculation: report of a round table conference pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome lung structure and function in different stages of severe adult respiratory distress syndrome redistribution of pulmonary blood flow in the dog with peep ventilation the association between physiologic dead-space fraction and mortality in subjects with ards enrolled in a prospective multi-center clinical trial lung inhomogeneity in patients with acute respiratory distress syndrome microvascular perfusion as a target for fluid resuscitation in experimental circulatory shock early bedside detection of pulmonary vascular occlusion during acute respiratory failure vascular obstruction causes pulmonary hypertension in severe acute respiratory failure alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia the pulmonary vascular lesions of the adult respiratory distress syndrome relationship between capillary and systemic venous po during nonhypoxic and hypoxic ventilation mechanisms of physiological dead space response to peep after acute oleic acid lung injury assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study effect of anatomic shunt on physiologic deadspace-to-tidal volume ratio-a new equation rationale of dead space measurement by volumetric capnography effect of lung recruitment and titrated positive end-expiratory pressure (peep) vs low peep on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors thank dr. fernando rosso (cic, fundación valle del lili-universidad icesi, cali, colombia) and dr. yuri takeuchi (universidad icesi -fundación valle del lili) for their unconditional support to this project. literature search: gaot, dfb and gh; data acquisition: gaot, dfb, jdv, wfb, and hjm; data analysis and interpretation: gaot, gh, hjm, jdv, wfb, eq, lect; critical review: gaot, gh, ab and ddb; conception, hypothesis delineation, and design of the study: gaot, and ddb. all authors read and approved the final manuscript. the current study received logistic support from the centro de investigaciones clínicas -fundación valle del lili, cali -colombia. the datasets generated and/or analyzed during the current study are not publicly available as recommended by the local ethical and research committee involving human beings (fundación valle del lili, cali, colombia) but these could be available from the corresponding author on reasonable request and under prior approval by such committee. the ethical and research committee involving human beings approved the current study (protocol number: ; approval number: - , , fundación valle del lili, cali, colombia). not applicable. key: cord- -sb pgqi authors: ospina-tascón, gustavo a.; teboul, jean-louis; hernandez, glenn; alvarez, ingrid; sánchez-ortiz, alvaro i.; calderón-tapia, luis e.; manzano-nunez, ramiro; quiñones, edgardo; madriñan-navia, humberto j.; ruiz, juan e.; aldana, josé l.; bakker, jan title: diastolic shock index and clinical outcomes in patients with septic shock date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: sb pgqi background: loss of vascular tone is a key pathophysiological feature of septic shock. combination of gradual diastolic hypotension and tachycardia could reflect more serious vasodilatory conditions. we sought to evaluate the relationships between heart rate (hr) to diastolic arterial pressure (dap) ratios and clinical outcomes during early phases of septic shock. methods: diastolic shock index (dsi) was defined as the ratio between hr and dap. dsi calculated just before starting vasopressors (pre-vps/dsi) in a preliminary cohort of patients with septic shock (january to february ) and at vasopressor start (vps/dsi) in patients with septic shock included in a recent randomized controlled trial (andromeda-shock; march to april ) was partitioned into five quantiles to estimate the relative risks (rr) of death with respect to the mean risk of each population (assumed to be ). matched hr and dap subsamples were created to evaluate the effect of the individual components of the dsi on rrs. in addition, time-course of dsi and interaction between dsi and vasopressor dose (dsi*ne.dose) were compared between survivors and non-survivors from both populations, while roc curves were used to identify variables predicting mortality. finally, as exploratory observation, effect of early start of vasopressors was evaluated at each pre-vps/dsi quintile from the preliminary cohort. results: risk of death progressively increased at gradual increments of pre-vps/dsi or vps/dsi (one-way anova, p < . ). progressive dap decrease or hr increase was associated with higher mortality risks only when dsi concomitantly increased. areas under the roc curve for pre-vps/dsi, sofa and initial lactate were similar, while mean arterial pressure and systolic shock index showed poor performances to predict mortality. time-course of dsi and dsi*ne.dose was significantly higher in non-survivors from both populations (repeated-measures anova, p < . ). very early start of vasopressors exhibited an apparent benefit at higher pre-vps/dsi quintile. conclusions: dsi at pre-vasopressor and vasopressor start points might represent a very early identifier of patients at high risk of death. isolated dap or hr values do not clearly identify such risk. usefulness of dsi to trigger or to direct therapeutic interventions in early resuscitation of septic shock need to be addressed in future studies. definition of shock incorporates the presence of low arterial pressure in association with abnormalities in tissue perfusion leading to abnormal oxygen metabolism by the cells [ ] . because the intimate relationship between blood pressure and flow, operational definitions of shock include the fall of mean (map) and/or systolic arterial ospina-tascón et al. ann. intensive care ( ) : pressure (sap) [ , ] . nevertheless, alterations of pulse wave could grossly mirror, in some extend, the underlying mechanisms of acute circulatory failure implied in shock. for example, sap results particularly important to define cardiogenic shock [ ] , hemorrhagic [ ] or any type of shock with a hypovolemic component, since at very early stage of these conditions, sap and pulse pressure (pp) fall while diastolic arterial pressure tends to be sustained. however, hypotension observed during septic shock results from a complex interaction between vasodilation, relative and absolute hypovolemia, myocardial dysfunction, and altered blood flow distribution [ ] . in particular, vasodilation resulting from the failure of the vascular smooth muscle to constrict is one of the leading mechanisms associated with hypotension and tissue hypoperfusion in septic shock [ ] . in these cases, diastolic arterial pressure (dap) would better reflect vasodilation than sap or map. in healthy people, dap is mainly determined by vascular tone and it remains nearly constant from the ascending aorta to the peripheral vessels [ ] . thus, detection of low dap at peripheral vessels should reflect systemic vasodilation as long as aortic valve is competent. however, in general, dap is not considered for definition of septic shock, and with few exceptions, its relationship with clinical outcomes has not been widely described [ ] . important studies in patients with septic shock define hypotension in terms of map and sap values [ ] [ ] [ ] assuming the pivotal role of map [ ] or sap, on organ perfusion [ ] [ ] [ ] , in addition to the prognostic value of sustained low map values [ ] . nevertheless, evaluation of the loss of vascular tone through the severity of diastolic hypotension could have profound implications on therapeutic decisions since there are not robust clues to rapidly predict when hypotension will be sustainably corrected with fluid loading. thus, rapid assessment of severity of vasodilation could influence therapeutic decisions such as the early introduction of vasoactive agents [ ] , which theoretically would avoid unnecessary fluid administration while promptly restoring tissue perfusion. remarkably, dap should not be evaluated separately from heart rate. acute reductions in arterial pressure are compensated by increased sympathetic activity, although sometimes such compensation becomes maladaptive. this was the original rationale to indexing sap by heart rate (hr) during hemorrhagic shock and acute critical illness [ , ] , or indexing map by hr to detect myocardial hypoperfusion [ ] . likewise, as dap depends on vascular tone and the duration of the cardiac cycle [ ] , a combination of dap and hr could reflect the severity of circulatory dysfunction during vasodilatory conditions. thus, we evaluated the relationships between very early hr:dap ratios (i.e., the diastolic shock index, or dsi, calculated just before or at the start of vasopressor support) and clinical outcomes in patients with septic shock, hypothesizing that very early dsi values could promptly identify patients at high risk of unfavorable outcomes, while persistence of high dsi during the first hours of resuscitation could reflect more severe cardiovascular dysfunction. a total of patients were analyzed: a preliminary cohort of patients with sepsis requiring vasopressor support (january to february ) from one mixed-icu in a university hospital in colombia (fundación valle del lili, cali, colombia) and patients with septic shock included in a recent randomized controlled study (march to april ) conducted in hospitals in countries (argentina, chile, colombia, ecuador, uruguay), the andromeda-shock trial [ ] . the respective ethical and research committee involving human beings approved the use of the data obtained in both the initial cohort (protocol number , irb/ec approval number - , fundación valle del lili, cali, colombia) and the randomized controlled trial [ ] . septic shock was defined in the andromeda-shock population according to the third international consensus definitions for sepsis and septic shock (sepsis . ), which states septic shock as the combination of suspected infection accompanying life-threatening organ dysfunction, requirement of vasopressor therapy to elevate map ≥ mmhg and lactate > mmol/l despite adequate fluid resuscitation [ ] . meanwhile, patients from the preliminary cohort were included under the diagnostic criteria for septic shock stated in the surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: [ ] , based on the previous sccm/esicm/accp/ats/sis international sepsis definitions conference [ ] , valid during the period in which the database was constructed. exclusion criteria for preliminary cohort covered patients < -year old, pregnant women, patients with liver failure (protrombin time > s or international normalized ratio ≥ . and any hepatic encephalopathy), advanced liver cirrhosis (child-pugh c), acute/ chronic atrial fibrillation, presence of ventricular arrhythmia, use of definitive/transitory pacemaker and those with do-not-resuscitate orders. meanwhile, exclusion criteria for the andromeda-shock population are detailed elsewhere [ ] . dsi was calculated as the quotient between hr and dap registered just before the start of vasopressor therapy (pre-vps/dsi) in the preliminary cohort and at the randomization point in the andromeda-shock population (< h of septic shock diagnosis according to inclusion criteria), i.e., vps/dsi [ ] . then, dsi was subsequently calculated , , and h after the introduction of vasopressor support in both populations. time elapsed from the first hypotension episode and the first fluid load with resuscitative intention was registered in the preliminary cohort, while time elapsed from the diagnosis of septic shock up to randomization was recorded for the andromeda-shock population. most of the initial measurements (i.e., pre-vasopressor and at the start of vasopressor) were obtained by non-invasive techniques using an oscillometric brachial cuff, typically in those patients admitted from the emergency room and general wards. however, invasive pressures were registered later on, when an indwelling intra-arterial catheter was placed. the volume of resuscitation fluids was registered at pre-vps point, and then, , and h after in the preliminary cohort, and at the vps/dsi point, and h after in the andromeda-shock population. meanwhile, net fluid balance was recorded at and h after the start of vasopressors in both populations. the hr-to-sap ratio [ , ] was also calculated at same time points. multiple organ dysfunction was assessed using the sequential organ failure assessment score (sofa) [ ] , while ventilator-free days and requirement of acute renal replacement therapy were also registered. finally, as a simple exploratory observation, the effect of timing to start vasopressor support was evaluated in the preliminary cohort. a very early start of vasopressor was defined as the one started within the first hour of receiving the first fluid load with resuscitative intention such as it was recently reported [ ] . patients from the preliminary cohort followed an early quantitative resuscitation protocol adapted from the surviving sepsis campaign [ , ] , aimed in general to target (a) map ≥ mmhg; (b) urine output > . ml/ kg/h; (c) scvo ≥ %, when available; (d) normalization of lactate levels or decreasing of % every- h in lactate levels. a complete description of the resuscitation protocol and general management in such cohort is described elsewhere [ ] . meanwhile, patients collected from andromeda-shock trial were randomly allocated to peripheral perfusion-targeted resuscitation or lactate level-targeted resuscitation following a protocol described in detail elsewhere [ ] . first, dsi values, calculated just before the start of vasopressors (pre-vps/dsi) in the preliminary cohort or at the randomization point (vps/dsi) in the androm-eda-shock population, were partitioned into five quantiles to estimate the relative risks (rr) of death in relation to the mean risk of their respective population (assumed to be ). the mean risk and % confidence intervals at each dsi quintile were calculated after adjustment for the covariables: age, sofa score day- , apache ii, initial arterial lactate, and volume of resuscitation fluids received before start of vasopressors and from vasopressor start up to h after. then, new partitions were performed aiming to evaluate the effect of individual components of pre-vps/dsi or vps/dsi (i.e., dap and hr) on the relative risk of death, as follows: (a) into quintiles of progressively higher dap; (b) into quintiles of progressively higher hr; (c) re-stratifying each original quintile of dap into sub-clusters of dsi to extract patients with similar dsi values and therefore, simultaneous increasing of hr and dap. second, repeated-measures anova were used to evaluate differences in the time-course of dsi, mean arterial pressure, dap, hr, pulse pressure, and vasopressor doses between survivors and non-survivors at day- in both preliminary and andromeda-shock populations. similarly, the time-course of the product of dsi and dose of vasopressor (dsi*ne.dose) was compared between survivors and non-survivors at day- . third, receiver operating characteristic (roc) curves were used to identify the performance of variables at pre-vp point (for preliminary cohort) or at randomization point (for andromeda-shock), and h after, to predict mortality at day- and . such variables were pre-vps/dsi (or vps/dsi, in the case of patients from andromeda-shock), lactate, mean arterial pressure, sofa score, apache ii, and systolic shock index (hr:sap ratio). in addition, the interaction or product of dsi by the dose of vasopressor (dsi*ne. dose) was also included at points where the patients were under vasopressor support. fourth, the effect of very early start of vasopressors on mortality at day- in each quintile of pre-vps/dsi from the preliminary cohort was evaluated using a chi square test and additionally, logistic regression models adjusted by sofa score and initial lactate at each pre-vps/dsi quintile. a hosmer and lemeshow test was used to assess the goodness of fit in each model. a total of patients with septic shock were analyzed: patients from a preliminary cohort (additional file : figure s a ) and from the randomized controlled trial andromeda-shock (additional file : figure s b) . a strobe statement checklist for observational studies is provided in sdc additional file : table s . lengths of icu and hospital stay were ( - ) and days, respectively, in the preliminary cohort, while these were ( - ) and days in the andromeda-shock. overall mortality at days- and were . % and . % in the preliminary cohort, and . % and . % in the andromeda-shock. general characteristics of both preliminary cohort and andromeda-shock are presented in the table . progressive increases in pre-vasopressor dsi (pre-vps/ dsi) or dsi at vasopressor start (vps/dsi) were related with gradual increases in the relative risk of death at day- in the preliminary and andromeda-shock populations (fig. ). similar hr values were related with progressively lower risk of death as long as dap gradually increases, and consequently, dsi values decrease (fig. ) . likewise, similar dap values were related with progressively higher risk of mortality as long as hr gradually increases, and consequently, dsi also did (fig. ) . nevertheless, simultaneous increases in hr and dap with subsequent similar dsi values were related with similar risk of death (additional file : figure s ). a complete description for dsi, dap and hr partitioning is presented in the additional file : tables s , s . meanwhile, a complete description of general demographics, hemodynamics, lactate, renal replacement and mechanical ventilation requirements, resuscitation and cumulative fluids according to the pre-vps/dsi and vps/dsi in the preliminary cohort and andromeda-shock populations are presented in additional file : tables s , s . there were significant differences in the time-course of dsi between survivors and non-survivors at day- in both populations (repeated-measures anova, intersubjects difference p < . ) (fig. ) . similarly, the product of dsi and dose of norepinephrine (dsi*ne.dose) remained significantly high in non-survivors from both populations (repeated-measures anova, inter-subjects difference p < . ) (fig. ) . time-course of diastolic pressure, heart rate, mean arterial pressure, pulse pressure and systolic shock index for survivors and non-survivors are showed in additional file : figures s -s . pre-vps/dsi from preliminary cohort or vps/dsi from andromeda-shock depicted similar performance to predict mortality at day- and than other variables such as sofa score and initial lactate levels (additional file : figure s a-s b) . conversely, mean arterial pressure or isolated diastolic arterial pressure and the systolic shock index showed poor performance for such prediction. dsi and dsi*ne.dose at h showed again similar performances than sofa score and lactate values, while mean arterial pressure, diastolic arterial pressures and the systolic shock index depicted a poor performance to predict mortality at day- (additional file : figure s b-s b) . very early start of norepinephrine (i.e., norepinephrine started within the first hour of the first fluid load with resuscitative intention) was related with a lower mortality in higher pre-vps/dsi (i.e., the pre-vps/dsi quintile- ) (additional file : tables s , s ). our study retrieves four important findings: (a) progressively higher dsi values calculated just before or at the start of vasopressors are associated with a gradual increase in the risk of death in patients with septic shock; (b) isolated low dap or high hr values do not clearly identify such risk; (c) non-survivors evolve with persistently high dsi values while requiring higher doses of vasopressors and more resuscitation fluids than survivors; (d) pre-vps/dsi and vps/dsi showed similar performance to sofa score and initial lactate levels to predict mortality, while mean arterial pressure and systolic shock index did not. vasodilation plays a key role in the development of hypotension and tissue hypoperfusion in septic shock [ ] . dap reflects in part the vascular tone when aortic valve is competent. nevertheless, the duration of the cardiac cycle, the blood volume ejected to the aorta and the arterial compliance also influence dap [ ] . thus, under isovolemic conditions and constant arterial compliance, shortening diastolic times are associated with higher dap while a prolonged diastole leads to an opposite effect [ ] . consequently, simultaneous and opposite variations in dap and hr could suggest more severe cardiovascular dysfunction, with progressively high hr unable to compensate dap drops as a consequence of gradual decrease in vascular tone. supporting this, our data suggest that such progressively opposite changes in hr and dap represent more severe circulatory dysfunction with proportional increases in the relative risk of death. persistently low map [ , ] or dap [ ] have been related to worse outcomes in septic shock, while newonset prolonged sinus tachycardia as a consequence of sympathetic activity has been associated with increased major cardiovascular events, prolonged length of stay [ ] , and higher mortality rates [ ] . nevertheless, isolated dap or hr just before or at start of vasopressors was not clearly related with mortality in the preliminary cohort and andromeda-shock populations. figure s ). in addition, map, sap and "systolic shock index" (or, hr:sap ratio) were not related with mortality in both populations (additional file : figures s , s ) . we hypothesized that although map and sap are used to operatively define septic and another types of shock, initial map or sap does not reflect systemic vasodilation, which is a leading mechanism in septic shock. although dsi depicted a similar auc-roc than sofa score and initial lactate levels, dsi could add some practical and valuable information about how to intervene the initial hemodynamic condition in sepsis. progressively high dsi values calculated just before and at the start of vasopressor support were related with gradual increases in the risk of death. patients in the higher quintiles of pre-vps/dsi and vps/dsi required more renal replacement therapy, depicted higher lactate values and also showed slower lactate decreases over the first h of resuscitation. they also required significantly more resuscitation fluids and higher doses of fig. relative risk of death at day- according to pre-vasopressor diastolic shock index (pre-vps/dsi) or vasopressor start (vps/dsi) partitions in the preliminary and andromeda shock populations. diastolic shock index values obtained from just before the start of vasopressor (in preliminary cohort) and at the start vasopressor support (in andromeda-shock) were partitioned into quantiles (q to q ). distribution of heart rate (hr) and diastolic pressure (dap) (top) and their respective diastolic shock index distribution (middle) are presented through the quantile distribution. boxplots (top and middle) delineate the interquartile range, the median is shown as a line in the middle of the box, and tails represent the % range. coefficients derived from a logistical regression were used to calculate the cut-off value of the diastolic shock index (dsi) detecting the mean risk of mortality of the entire population at days. this point was used as the reference to calculate the adjusted relative risks, in such a way that a relative risk of represents the mean risk of the respective population (bottom). the mean risk and % confidence interval (error bars at the bottom) for each percentile were calculated after multivariate adjustment (cox proportional-hazards model) for the covariables: age, gender, sofa score day- , initial arterial lactate and ph, and resuscitation fluids from vp to h. the gray zone represents the % confidence interval for the cox regression (continuous line) across the complete population, assuming the diastolic shock index as a continuous variable. note that adjusted relative risk of death increases as diastolic shock index also does through the quintile distribution vasopressors as reflected by the product of dsi and dose of norepinephrine (dsi*ne.dose). we hypothesize that persistently higher dsi values reflect a lack of vascular tone requiring progressively higher doses of vasopressors with an inadequate restoration of tissue perfusion. however, the observational nature of our study hinders the direct effect of variations in vasopressor dose or fluid loading on the dsi since the resuscitation maneuvers in each group were guided targeting map but not dap. all arterial pressure measurements used for dsi calculations in our study were obviously obtained at the peripheral circulation (i.e., at brachial, femoral or radial sites). although some disagreement in systolic or mean arterial pressure is observed from the ascending aorta to the peripheral vessels, dap remains almost constant [ , ] , even during experimental endotoxemic conditions in which a "vascular tone decoupling" from central-toperipheral circulation can occur [ ] . thus, dap records obtained at peripheral circulation closely reflect central dap measurements even during severe inflammatory conditions with increased vasodilation and altered arterial compliance. although it could be argued that invasive vs. non-invasive measurement methods to measure arterial pressure could influence our results, the bias for dap measurements is far lower than that observed for sap [ ] . furthermore, although significant differences fig. relative risk of death at day- according to diastolic arterial pressure (dap) partition in the preliminary and andromeda shock populations. diastolic arterial pressure (dap) values from just before the start of vasopressor support were partitioned into quantiles (q to q ). distribution of heart rate (hr) and diastolic pressure (dap) (top) displays a progressive increasing of dap values through the quantile partitioning with their corresponding hr values, which remains similar from q to q . the respective diastolic shock index distribution (middle) is presented through the quantile distribution. the boxes (top) delineate the interquartile range, the median is shown as a line in the middle of the box, and tails represent the % range. boxplots/error bars (middle) represent medians and % confidence intervals of the diastolic shock index (dsi) at each quantile. relative risks' distributions (bottom) were calculated as described in fig. . note that adjusted relative risk of death decreases as dap increases and subsequently dsi decreases, for similar hr values in sap or map are observed according to if invasive vs. non-invasive method are used [ ] , dap recordings are closer at progressively lower dap values [ ] . consequently, all these considerations claim against the introduction of considerable errors in dsi calculation when using invasive vs. non-invasive dap values and also favor the notion of dsi as a global marker of decreased vascular tone since dap is less influenced by the reflection of pulse waves. this study may have some important clinical implications. it is unlikely that severe hypotension as a result of severe vasodilation could be reversed by simple fluid administration and instead, unnecessary fluids with subsequent harmful accumulation can occur [ , ] . although also considered as "first line intervention", vasopressors are usually used as a rescue therapy when initial fluid administration fails to correct hypotension or when arterial pressure is judged to be insufficient to ensure an adequate tissue perfusion. recent experimental and observational data suggest that very early start of vasopressor support could be beneficial [ , ] . nevertheless, there are no clear signals indicating when vasopressor support should be started. in this way, very early signals of severe vasodilation should alert on its possible immediate requirement. thus, dsi should not be interpreted as "another index of death". instead, a higher dsi value at presentation of severe cases of sepsis could identify patients who might benefit from some fig. relative risk of death at day- according to heart rate (hr) partition the preliminary and andromeda shock populations. heart rate (hr) values from just before the start of vasopressor support were partitioned into quantiles (q to q ). distribution of heart rate (hr) and diastolic pressure (dap) (top) displays a progressive increasing of hr values through the quantile partitioning with their corresponding dap values, which remains similar from q to q . the respective diastolic shock index distribution (middle) is presented through the quantile distribution. the boxes (top) delineate the interquartile range, the median is shown as a line in the middle of the box, and tails represent the % range. boxplots/error bars (middle) represent medians and % confidence intervals of the diastolic shock index (dsi) at each quantile. relative risks' distributions (bottom) were calculated as described in fig. . note that adjusted relative risk of death increases as hr and subsequently dsi also increases, for similar dap values very early interventions capable of modifying the course of septic shock. our data suggest some beneficial of very early start of vasopressors in patients at the higher pre-vps dsi. nevertheless, sample size and the retrospective nature of such observation simply pose a hypothesis to be tested in the future. our study has several limitations. first, as previously mentioned, its retrospective nature might limit the conclusions since some confounding factors and potential bias may not have been controlled. nevertheless, observations from preliminary cohort, corroborated in prospectively collected data from a recent randomized controlled trial, reinforce the strength of dsi as an early identifier of septic patients at high risk of death. second, we did not include a control group of normal subjects, so recognizing a dsi cutoff to identify abnormality could be misleading. third, although persistently high dsi values were consistently observed in non-survivors in both the preliminary and andromeda-shock groups, there are no clues about whether it is possible to intervene dsi course or even whether modifying dsi course might influence clinical outcomes. nevertheless, this could be an important research question as recent experimental observations suggest that some early therapeutic interventions might modify the time-course of cardiovascular dysfunction in septic shock. finally, despite the apparent plausibility of dsi at very early stages of septic shock, our observations are limited to a relative small sample of patients. consequently, the potential utility of dsi in the clinical practice should be additionally explored. dsi calculated just before or at the vasopressor start might identify patients with septic shock at high risk of death. isolated dap or high hr is not clearly related with such risk. whether the dsi could be used as a trigger or to direct therapeutic interventions in septic shock or sepsis-related cardiovascular dysfunction deserves future research efforts. consensus on circulatory shock and hemodynamic monitoring. task force of the european society of intensive care medicine contemporary management of cardiogenic shock: a scientific statement from the american heart association effect of blood pressure on hemorrhage volume and survival in a near-fatal hemorrhage model incorporating a vascular injury circulatory shock abnormal vascular tone, defective oxygen transport and myocardial failure in human septic shock the patterns of the arterial pressure pulse diastolic arterial blood pressure: a reliable early predictor of survival in human septic shock trial of early, goal-directed resuscitation for septic shock goal-directed resuscitation for patients with early septic shock a randomized trial of protocol-based care for early septic shock hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature n-acetyl-l-cysteine depresses cardiac performance in patients with septic shock elevation of cardiac output and oxygen delivery improves outcome in septic shock reversal of late septic shock with supraphysiologic doses of hydrocortisone hemodynamic variables related to outcome in septic shock temporary removal: importance of diastolic arterial pressure in septic shock: pro shock index as a marker for significant injury in trauma patients shock index: a re-evaluation in acute circulatory failure the quotient of mean arterial pressure and heart rate predicts hypoperfusion of collateral-dependent myocardium steady and pulsatile energy losses in the systemic circulation under normal conditions and in simulated arterial disease. cardiovasc res effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on -day mortality among patients with septic shock: the andromeda-shock randomized clinical trial the third international consensus definitions for sepsis and septic shock (sepsis- ) surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock sccm/esicm/accp/ats/sis international sepsis definitions conference dmw-deutsche medizinische wochenschrift use of the sofa score to assess the incidence of organ dysfunction/ failure in intensive care units: results of a multicenter, prospective study. working group on "sepsis-related problems" of the european society of intensive care medicine effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis surviving sepsis campaign: international guidelines for management of sepsis and septic shock combination of arterial lactate levels and venous-arterial co to arterial-venous o content difference ratio as markers of resuscitation in patients with septic shock early goal-directed therapy using a physiological holistic view: the andromeda-shock-a randomized controlled trial arterial blood pressure during early sepsis and outcome impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications significance of new-onset prolonged sinus tachycardia in a medical intensive care unit: a prospective observational study pressure and flow waves in systemic arteries and the anatomical design of the arterial system peripheral vascular decoupling in porcine endotoxic shock methods of blood pressure measurement in the icu fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database deresuscitation of patients with iatrogenic fluid overload is associated with reduced mortality in critical illness unintended consequences; fluid resuscitation worsens shock in an ovine model of endotoxemia publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors thank dr. sergio prada (cic, fundación valle del lili-universidad icesi, cali, colombia) and dra. yuri takeuchi (universidad icesi -fundación valle del lili) for their unconditional support to this project. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . abbreviations hr: heart rate; dap: diastolic arterial pressure; map: mean arterial pressure; sap: systolic arterial pressure; dsi: diastolic shock index; sofa: sequential organ failure assessment score; apache ii: acute physiology and chronic health evaluation. the current study received logistic support from the centro de investigaciones clínicas -fundación valle del lili, cali -colombia. the datasets generated and/or analyzed during the current study are not publicly available as recommended by the local ethical and research committee involving human beings (fundación valle del lili, cali, colombia). nevertheless, it could be available from the corresponding author on reasonable request and under prior approval by such committee. the ethical and research committee involving human beings approved the current study (protocol number , irb/ec approval number - , fundación valle del lili, cali, colombia).the andromeda-shock randomized clinical trial was conducted at hospitals in countries (argentina, chile, colombia, ecuador, uruguay). the institutional review board at each site approved the study and the use of data for post hoc analysis. not applicable. the authors declare that they have no competing interests. received: january accepted: april key: cord- - nsvup authors: kapoor, indu; prabhakar, hemanshu; mahajan, charu title: vitamins as adjunctive treatment for coronavirus disease! date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: nsvup nan we read with great interest the article by li et al., where authors have reviewed many therapeutic strategies for critically ill patients with coronavirus disease (covid- ) [ ] . apart from antiviral drugs and anti-bacterial drugs, authors also discussed various adjunctive interventions which included corticosteroids, thymosin alpha a, cyclosporine a, interferons, gamma globulins and many more. they even discussed the chinese medicines which were used in past to treat other viral infections. they also stated that these medicines might benefit covid- patients; however, the efficacy and safety of these traditional medicine formulae in covid- need to be further confirmed by clinical trials. though authors have not mentioned, another important supplementary adjunct to treat these critically ill patients in intensive care unit is various vitamins. at present times, good immune system is the major weapon against the covid- and vitamins help in efficient functioning of immune system. inadequacy of these vitamins in the body can lead to suppressed immunity, which may further predisposes the patient towards infection. these vitamins enhance the three level of immunity in body's defence system by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. vitamins like a, c and e help in enhancing the skin barrier function. vitamins a, b , b , c, d and e work synergistically to support the protective activities of the immune cells. all these vitamins except vitamin c are helpful in antibody production. vitamin a has been shown to enhance immune response against influenza virus [ ] . a controlled human trial has reported that vitamin c significantly lowers the incidence of pneumonia, suggesting that vitamin c may affect susceptibility to lower respiratory tract infections [ ] . kim et al. in their study indicated that combined use of vitamin c, hydrocortisone, and thiamine (vitamin b ) improves the chest radiologic findings of patients with severe pneumonia and reduce their mortality [ ] . ilie et al. identified a negative association between the mean vitamin d levels in various european countries with covid- cases/ m and covid- mortality [ ] . the most vulnerable group, the elderly population, is also the amongst the ones who have the most deficient vitamin d levels and are at higher risk for covid- infection. a large systematic review and meta-analysis including , patients has also shown that vitamin d supplementation is effective against acute respiratory tract infection [ ] . therefore, these vitamins have shown to protect against the acute viral infections and should be the part of adjunctive therapy in critically ill covid- patients. despite the use of vitamins worldwide in covid- patients, it is difficult to comment on its absolute therapeutic or preventive role in these group of patients. in future, trials may be needed to understand the role of vitamins in patients of covid- . therapeutic strategies for critically ill patients with covid- baseline serum vitamin a and d levels determine benefit of oral vitamin a&d supplements to humoral immune responses following pediatric influenza vaccination vitamin c intake and susceptibility to pneumonia combined vitamin c, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: propensity score-based analysis of a before-after cohort study the role of vitamin d in the prevention of coronavirus disease infection and mortality vitamin d supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data ik: this author helped in conceptualization of the manuscript and prepared the first draft. hp: this author helped in finalising the manuscript. cm: this author helped in revising the manuscript. all authors read and approved the final manuscript. none. the authors declare that they have no competing interests.received: june accepted: september open access *correspondence: dr.indu.me@gmail.com aiims, new delhi, india key: cord- -jjszkq n authors: gavelli, francesco; teboul, jean-louis; azzolina, danila; beurton, alexandra; taccheri, temistocle; adda, imane; lai, christopher; avanzi, gian carlo; monnet, xavier title: transpulmonary thermodilution detects rapid and reversible increases in lung water induced by positive end-expiratory pressure in acute respiratory distress syndrome date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: jjszkq n purpose: it has been suggested that, by recruiting lung regions and enlarging the distribution volume of the cold indicator, increasing the positive end-expiratory pressure (peep) may lead to an artefactual overestimation of extravascular lung water (evlw) by transpulmonary thermodilution (tptd). methods: in ards patients, we measured evlw (picco device) at a peep level set to reach a plateau pressure of cmh( )o (highpeep(start)) and and min after decreasing peep to cmh( )o (lowpeep( ′) and lowpeep( ′), respectively). then, we increased peep back to the baseline level (highpeep(end)). between highpeep(start) and lowpeep( ′), we estimated the degree of lung derecruitment either by measuring changes in the compliance of the respiratory system (crs) in the whole population, or by measuring the lung derecruited volume in patients. we defined patients with a large derecruitment from the other ones as patients in whom the crs changes and the measured derecruited volume were larger than the median of these variables observed in the whole population. results: reducing peep from highpeep(start) ( ± cmh( )o) to lowpeep( ′) significantly decreased evlw from ± to ± ml/kg, central venous pressure (cvp) from ± to ± mmhg, the arterial oxygen tension over inspired oxygen fraction (pao( )/fio( )) ratio from ± to ± mmhg and lung volume by [ – ] ml. the evlw decrease was similar in “large derecruiters” and the other patients. when peep was re-increased to highpeep(end), cvp, pao( )/fio( ) and evlw significantly re-increased. at linear mixed effect model, evlw changes were significantly determined only by changes in peep and cvp (p < . and p = . , respectively, n = ). when the same analysis was performed by estimating recruitment according to lung volume changes (n = ), cvp remained significantly associated to the changes in evlw (p < . ). conclusions: in ards patients, changing the peep level induced parallel, small and reversible changes in evlw. these changes were not due to an artefact of the tptd technique and were likely due to the peep-induced changes in cvp, which is the backward pressure of the lung lymphatic drainage. trial registration id rcb: -a - . registered october extravascular lung water (evlw) is the amount of fluid present in the lungs, outside the pulmonary blood vessels [ ] . in acute respiratory distress syndrome (ards), lung injury leads to increases in the pulmonary capillary permeability and in evlw, which reflect the severity of the disease [ ] . many studies have investigated the changes in evlw induced by a positive end-expiratory pressure (peep), which is the cornerstone of ards treatment (additional file : table s ). however, they have provided very discordant results, some showing that evlw augmented when increasing levels of peep were applied [ ] [ ] [ ] [ ] [ ] [ ] , some that it decreased [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and some others that it did not change [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the large majority of these studies were conducted in animals [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , with various models of ards and methods of evlw estimation. today, the routine measurement of evlw at the bedside is allowed by transpulmonary thermodilution (tptd). one animal [ ] and three human studies [ , , ] have investigated the effects of peep changes on tptd-estimated evlw, three suggesting that evlw increases with peep [ ] [ ] [ ] and another one that it remains unchanged [ ] . however, these studies did not investigate the potential artefact that may induce an increase in evlw along with the peep level. indeed, the peep-induced lung recruitment may relieve the hypoxic vasoconstriction of the recruited regions, which eventually become accessible to the cold indicator while they were not at a lower peep level. this may lead to an artefactual overestimation of the peepinduced evlw augmentation. thus, the goal of our study, conducted in ards patients, was to investigate whether the estimation of evlw by tptd is artefactually influenced by the lung derecruitment potentially secondary to the decrease in the peep level. this prospective, one-centre study was approved by the institutional review board of our institution (comité pour la protection des personnes, ile-de-france vii, idcrb -a - ). at the time of inclusion, patients' relatives were informed of the study protocol and possibility was given to them to refuse participation. as soon as clinical condition improved and patients were able to give consent, the same information was delivered to them, with possibility for them to deny the participation. all patients and/or relatives accepted to participate. inclusion criteria were age ≥ years, presence of ards according to the berlin definition [ ] and monitoring with a tptd device (picco device, pulsion medical systems, feldkirchen, germany). exclusion criteria were contraindications to peep increase (pneumothorax, uncontrolled shock state) and extracorporeal membrane oxygenation, which impedes the measurement of evlw by tptd. patients could be under continuous venovenous haemofiltration since it does not affect the tptd estimation of evlw [ , ] . tptd measurements were performed by injecting -ml boluses of saline (< °c) through a jugular vein catheter. in order to allow the detection of small changes in evlw, the average of the results obtained by five successive thermodilution measurements was used. with this number of replicates, the least significant change of evlw is % [ ] . with tptd, we also measured the pulmonary vascular permeability index (pvpi) [ , ] (also averaged from five successive thermodilution measurements) and cardiac index (ci). in addition to arterial pressure and ci, we measured the central venous pressure (cvp) at the base of the c wave, at end-expiration. the value of three successive respiratory cycles was averaged. the pressure transducer was attached to the arm, at a height corresponding to the level of the right atrium. in a subgroup of patients ventilated with an infinity v ventilator (dräger, lübeck, germany), we directly estimated the volume of derecruited lung during the peep decrease. for this purpose, after transiently reducing the respiratory rate to breaths/min to reduce the risk of air trapping, a prolonged expiration was performed while abruptly reducing peep from its baseline value to cmh o for one breath. the difference in end-expiratory vt between the breath while peep was decreased and the one before was defined as the total change in lung volume [ ] . at the same time, we keywords: pulmonary oedema, pulmonary lymphatic drainage, central venous pressure, lung recruitment, mechanical ventilation estimated the minimal predicted change in lung volume determined by the peep change, as previously described [ ] . briefly, the respiratory system compliance at low peep was multiplied by the pressure difference between the two peep levels. then, this value was subtracted from the total change in lung volume and the result was considered as an estimation of derecruited lung volume induced by peep reduction [ , ] . in addition, in the whole population, we estimated the degree of derecruitment during the peep decrease by observing the simultaneous changes in compliance of the respiratory system (crs) [ ] . for this purpose, crs was calculated as the ratio of tidal volume (vt) over the driving pressure (plateau pressure-peep). we defined patients with a large derecruitment from the other ones as patients in whom crs changes and the measured derecruited volume were larger than the median of their value observed in the whole population. at baseline, patients were ventilated in the assist-control mode with a vt at ml/kg (predicted body weight). peep was set to reach a plateau pressure of - cmh o (high-peep) [ ] . sedation was provided by propofol and remifentanil. at this time (high-peep start ), a first set of measurements was performed including heart rate, arterial pressure, cvp, evlw and blood gas analysis. peep was then decreased, while the derecruited volume was estimated in the patients in whom it was possible. after min (low-peep ′ ) and min (low-peep ′ ), we measured the same variables as at baseline. a time interval of min appeared to us as reasonably long enough for allowing potential fluid transfer through the pulmonary capillary barrier. thereafter, peep was increased back to its baseline level. after min, the variables measured at baseline were measured again (high-peep end ). sedative drugs, vt, respiratory rate, and the fraction of inspired oxygen (fio ) remained unchanged during the study. volume expansion, fluid removal, recruitment manoeuvres, administration of inhaled nitric oxide or nebulization were not performed during this time. considering an α risk of % and a β risk of %, to evidence a peep-induced change in evlw by ± ml/kg, we estimated that patients should be included into the study, a number that was rounded to . the peepinduced change in evlw was estimated by considering that the least significant change of the measurement is % if five values of tptd are averaged [ ] and by expecting a baseline evlw of ± ml/kg [ ] . data are expressed as mean ± standard deviation for normally distributed variables or median [interquartile range] for skewed data. a shapiro-wilk test was considered to determine if a variable was well-modelled by a normal distribution. the analysis of patients with a large derecruitment compared to the other ones was planned a priori. a linear mixed factor anova for repeated measurements was used to evaluate both within-subject effect (peep/time effect) and between-subject effects (recruiting effect). both high-peep start and low-peep ′ have been considered as reference categories for comparisons. multiple comparisons of means have been performed using tukey contrasts. the covariate effect on evlw outcome was then estimated using a linear mixed model for repeated measurements (random intercept model) adjusting the estimates for peep, position (prone/supine) and recruiting effect according either to the crs changes and the recruited lung volume. sample size calculation and statistical analysis were performed with medcalc . . software (mariakerke, belgium) and r . . statistical software with lme package. sixty consecutive patients were included. on average, ards developed for [ ] [ ] [ ] [ ] [ ] days at the time of inclusion. septic shock was present in ( %) patients (table ) . pneumonia was the cause of ards in all patients. the number of chest x-ray quadrants involved was two in ( %) cases, three in ( %) cases and four in ( %) patients. at baseline, blood lactate was . [ . - . ] mmol/l, creatinine [ - ] μmol/l and ( %) patients had renal replacement therapy in place (conventional haemodialysis in three, continuous venovenous hemofiltration in patients, without weight loss). eleven ( %) patients were in prone position at the time of inclusion, whereas ( %) other ones had required prone positioning before the inclusion (table ). seventeen ( %) patients were paralysed at the time of inclusion and the richmond agitation-sedation scale was − [− to − ]. the decrease in peep from high-peep start decreased cvp by ± % (p < . ) ( table ). when peep was increased from low-peep ′ to high-peep end , opposite and symmetrical changes were observed (table ; see additional file : table s for post hoc comparisons). from high-peep start to low-peep ′ , peep decreased by ± cmh o and this was accompanied by a decrease in the plateau pressure by ± cmh o. when decreasing peep from high-peep start , the change in crs was . [− . to . ] ml/cmh o (n = ) ( table ) . since the median value of crs changes was . ml/ cmh o, we defined derecruiters as patients in whom decreasing peep induced a decrease in crs. when decreasing peep from high-peep start , the estimated derecruited lung volume was [ - ] ml in the patients in whom it was measured (n = ). no differences were found in terms of evlw changes between derecruiters and the other patients, defined according to either the crs change (n = ) or the derecruited volume (n = ). all the significant changes in respiratory variables reversed with a similar amplitude when peep was increased from low-peep ′ to high-peep end ( table ) . decreasing peep from high-peep start induced a significant decrease in evlw by ± % (p < . ) ( table , fig. ). this decrease in evlw was observed in all the patients but two (fig. ) . it persisted at low-peep ′ and low-peep ′ . when peep was increased from low-peep ′ to high-peep end , opposite and symmetrical changes in evlw were observed (table ) . when we evaluated the covariate effect on evlw at the linear mixed model for repeated measures, adjusted for peep, prone/supine position and recruitment according to crs changes, only the changes in peep and cvp were significantly associated to the changes in evlw (p < . and p = . , respectively) ( table ). when we performed the same analysis by estimating recruitment according to lung volume changes (n = ), cvp but not the recruited lung volume remained significantly associated to the changes in evlw (p < . ). this study shows that decreasing peep in ards patients induces a small, reversible and rapid decrease in evlw measured by tptd. the recruited lung volume was not independently associated with this change in evlw, while it was the case for the change in cvp. at the bedside, the only technique that allows the measurement of evlw is tptd. although it can detect interstitial oedema, lung ultrasound does not allow the quantification of the evlw total volume, and ct scan cannot be used routinely. the estimation of evlw by tptd in humans has been demonstrated to correlate with the one provided by gravimetry [ ] , which is the reference technique. even small and rapid changes in evlw can be measured [ ] . the value of evlw has been regularly demonstrated to be correlated with mortality in critically ill patients [ , ] , especially in septic shock [ , ] and ards [ , ] . nevertheless, the ability of tptd to assess the changes in evlw induced by peep has been only scarcely investigated, despite its important role in ards management [ ] . moreover, the few available studies did not specifically investigate the artefact that may affect the tptd estimation of peep-induced changes in evlw [ ] [ ] [ ] ] . as a matter of fact, by relieving the hypoxic vasoconstriction in recruited areas, peep may allow the cold indicator to reach these regions, increasing the volume of evlw that is accessible to measurement. in our study, the changes in evlw were the same among patients with high or low derecruitment, when derecruitment was assessed by the peep-induced change in lung volume, the method that is today the best one for estimating recruitment/derecruitment at the bedside [ ] . it was also the same in the whole population, when we defined derecruitment as a decrease in crs. moreover, neither the estimated derecruited lung volume nor the crs changes were independently associated with evlw changes at linear mixed model analysis. another argument against the explanation of evlw changes by artefacts due to lung recruitment is that the changes in evlw were observed rapidly both after [ ] . the fact that specular changes were observed after opposite peep changes strongly suggests that a haemodynamic mechanism may be a more plausible explanation for the observed results. since the peep-induced changes in evlw we observed were not due to artefacts in the tptd estimation, one should consider that evlw was really decreased when the peep level was reduced, and that this small and rapid change was reversible. although of small amplitude, the evlw changes were actually significant. moreover, fig. shows well how evlw changes were very consistent among patients. also, we took the precaution to measure evlw by averaging not three but five tptd measurements, which enabled us to reliably detect small changes in evlw [ ] . our results are in accordance with the previous studies which, amongst very discrepant ones, suggested that peep induces small increases in evlw [ ] [ ] [ ] [ ] [ ] [ ] . in theory, three mechanisms might explain why evlw varies in the same direction as peep (additional file : figure s ). first, decreasing peep decreases cvp, which is the backward pressure of the drainage through the thoracic duct. this may happen by direct transmission of the intrathoracic pressure to the right atrial pressure, or as the result of the decrease in the right ventricular afterload. although the changes in evlw were of lower amplitude than those of cvp, the results of the linear mixed effect model make this pathophysiological hypothesis acceptable. of note, even though it may increase cvp in ards patients [ , ] , prone position in our population was not an element influencing the relationship between cvp and evlw. the second mechanism which may explain why the peep decrease diminished evlw is a decrease in the formation of lung water (additional file : figure s ). indeed, the intrathoracic pressure is transmitted to the left atrium, such that when peep is decreased, the intramural pulmonary capillary pressure is decreased as well. it is well known that, on the opposite, augmenting peep increases the intramural pulmonary artery occlusion pressure [ ] . we could not assess this mechanism, since we estimated neither the pulmonary capillary pressure nor the pulmonary artery occlusion pressure in our study. the normal pulmonary lymphatic flow is estimated to be - ml/h in humans [ ] . nevertheless, it has been reported that the pulmonary lymphatic flow could increase to tenfold, or even more, during ards [ ] . moreover, the estimation of pulmonary lymphatic flow in humans comes from animal studies, and it is much of an assumption that lymph flow is the same per kilogram of bodyweight in humans as in dogs [ ] . then, this is compatible with the amount of changes in evlw we observed. the peep decrease led to a reduction of evlw by . ± . ml/kg, which was equivalent to roughly ml of lung water accumulated in min, and vice versa when peep was re-increased. nevertheless, since we did not directly measure the lymphatic flow and since the link between evlw and cvp observed in our results was imperfect, we cannot exclude the contribution of other mechanisms. in particular, it might be possible that part of the changes in evlw we observed were related to changes in lung permeability, although this seems to be unlikely in such a short time. the decrease in peep was associated with a significant but slight decrease in pvpi, which reflects alveolo-capillary permeability. nevertheless, this change was very small, and was not significantly reversed when peep was re-increased. first, our findings show that tptd is not flawed by the level of peep, as it has been previously suspected [ ] . second, our observation that increasing peep increases evlw does not challenge the benefit of peep in ards. the increase in evlw we report was small and might be easily counterbalanced by the potential benefits of peep such as increase in end-expiratory lung volume induced by recruitment, decrease in pulmonary shunt in recruiters and redistribution of alveolar fluid to extra-alveolar spaces [ ] . nevertheless, when using tptd at the bedside [ ] , clinicians should be aware that changing peep might slightly change evlw and that it is not due to a worsening of the disease or to the deleterious effects of some fluid administration. first, we only observed the short-term effects of peep. we judged it was ethically unacceptable to maintain these patients with ards at a low peep level for a long time. moreover, it would have been impossible to avoid confounding events (changes in ventilatory setting and fluid administration or removal) over longer periods. second, we estimated the derecruited volume during the peep decrease and not the recruited volume during the peep re-increase. indeed, we speculated that derecruitment may occur faster than recruitment and be easier to detect [ ] . third, we directly measured the peep-induced changes in lung volume in patients only, though it is the best method to estimate lung recruitment or derecruitment at the bedside. estimating derecruitment through changes in crs, as we did in the whole population, has many limitations [ ] . fourth, the number of saline boluses required for averaging evlw measurements may have provoked fluid-induced changes in evlw. however, the fact that evlw decreased at the first study step indicates that this limitation probably had a very small impact. fifth, because this was a human study, we could not directly measure the lymphatic flow, a procedure that could have strengthened our conclusions. finally, we did not insert either a pulmonary artery catheter or an oesophageal balloon and thus could not estimate the hydrostatic lung filtration pressure and the transmural pressure. we thus cannot exclude that changing peep also changed the degree of pulmonary oedema formation. in ards patients, changing the peep level induced parallel, small and reversible changes in evlw. these changes were not due to an artefact of the tptd technique and are likely due to the peep-induced changes in cvp. extravascular lung water in critical care: recent advances and clinical applications relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the berlin definition aspiration pneumonia: beneficial and harmful effects of positive end-expiratory pressure effect of 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patients with hyperinflation lymphatics and lymph in acute lung injury effects of peep on extravascular lung water and central blood volume in the dog indicator dilution measurements of extravascular lung water: basic assumptions and observations consensus on circulatory shock and hemodynamic monitoring. task force of the european society of intensive care medicine publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : table s . previous literature regarding positive endexpiratory pressure effects on lung water in acute respiratory distress syndrome.additional file : table s . mean difference of haemodynamic and respiratory variables for post hoc comparisons using tukey hsd approach.additional file : figure s . possible haemodynamic effects of positive end-expiratory pressure (peep) decrease on extravascular lung water (evlw) levels, not taking into consideration possible artefactual effects related to the transpulmonary thermodilution (tptd) method. ards: acute respiratory distress syndrome; cvp: central venous pressure; ci: cardiac index; crs: respiratory system compliance; evlw: extravascular lung water; fio : inspired oxygen fraction; pao : arterial oxygen partial pressure; pao /fio : arterial oxygen tension over inspired oxygen fraction ratio; peep: positive end-expiratory pressure; pplateau: plateau pressure; pvpi: pulmonary vascular permeability index; sao : arterial oxygen saturation; tptd: transpulmonary thermodilution; vt: tidal volume. jlt and xm conceived and designed the study. ab, cl, fg, ia and tt recruited the patients and collected the data. da, fg, jlt and xm analysed and interpreted the data. gca supervised the data interpretation. fg and xm drafted the report and all authors contributed to review it. all authors read and approved the final manuscript. no funding. individual, de-identified participant data are available from the corresponding author on reasonable request. information and consent obtained for each patient.name of the ethics committee that approved the study and the committee's reference number: comité pour la protection des personnes, ile-de-france vii. trial registration id rcb: -a - . registered october . the patients were included prospectively. not applicable. key: cord- -ql moyi authors: hong, david; choi, ki hong; cho, yang hyun; cho, su hyun; park, so jin; kim, darae; park, taek kyu; lee, joo myung; song, young bin; choi, jin-oh; hahn, joo-yong; choi, seung-hyuk; choi, jin-ho; sung, kiick; gwon, hyeon-cheol; jeon, eun-seok; yang, jeong hoon title: multidisciplinary team approach in acute myocardial infarction patients undergoing veno-arterial extracorporeal membrane oxygenation date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: ql moyi background: limited data are available on the impact of a specialized extracorporeal membrane oxygenation (ecmo) team on clinical outcomes in patients with acute myocardial infarction (ami) complicated by cardiogenic shock (cs). this study evaluated whether specialized ecmo team is associated with improved in-hospital mortality in ami patients undergoing veno-arterial (va) ecmo. methods: a total of ami patients who underwent va-ecmo were included. in january , a multidisciplinary ecmo team was founded at our institution. eligible patients were classified into a pre-ecmo team group (n = ) and a post-ecmo team group (n = ). the primary outcome was in-hospital mortality. results: in-hospital mortality (pre-ecmo team vs. post-ecmo team, . % vs. . %; p = . ) and cardiac intensive care unit mortality (pre-ecmo team vs. post-ecmo team, . % vs. . %; p = . ) were significantly lower after the implementation of a multidisciplinary ecmo team. on multivariable logistic regression model, implementation of the multidisciplinary ecmo team was associated with reduction of in-hospital mortality [odds ratio: . , % confidence interval (ci) . – . ; p = . ]. incidence of all-cause mortality [ . % vs. . %; hazard ratio (hr): . , % ci . – . ; p < . ) and readmission due to heart failure ( . % vs. . %; hr: . , % ci . – . ; p = . ) at months of follow-up were also significantly lower in the post-ecmo team group than in the pre-ecmo team group. conclusions: implementation of a multidisciplinary ecmo team was associated with improved clinical outcomes in ami patients complicated by cs. our data support that a specialized ecmo team is indispensable for improving outcomes in patients with ami complicated by cs. cardiogenic shock (cs) is the main cause of mortality in patients with acute myocardial infarction (ami) [ , ] . despite advancements in reperfusion and pharmacological therapy, the short-term mortality rate of patients with ami complicated by cs remains unacceptably high [ , ] . particularly, in refractory cs not responding to open access *correspondence: jhysmc@gmail.com † david hong and ki hong choi contributed equally to this work division of cardiology, department of internal medicine, heart vascular stroke institute, samsung medical center, sungkyunkwan university school of medicine, irwon-ro, gangnam-gu, seoul , republic of korea full list of author information is available at the end of the article conventional medical therapies, in-hospital mortality rate reaches % to % [ , ] and mechanical support such as veno-arterial (va) extracorporeal membrane oxygenation (ecmo) is recommended in both the latest american heart association and the european society of cardiology guidelines (classes iia and iib, respectively) [ , ] . these poor outcomes are due to complex and hemodynamically diverse state of cardiogenic shock [ , ] . the high-acuity of maintaining ecmo and the interaction between native heart and va-ecmo may also be related to the poor outcomes [ , ] . in particular, running va-ecmo is associated with many serious complications, which may contribute to further increase in morbidity and mortality [ , [ ] [ ] [ ] . accordingly, related organizations recommended that these patients be managed by a collaborative multidisciplinary team with trained specialists [ , ] . however, for ami complicated by cs, which is the most common cause for the use of va-ecmo [ ] , the impact of a multidisciplinary approach on the clinical outcome has not been investigated. therefore, we sought to identify whether a multidisciplinary ecmo team is associated with improvements in in-hospital mortality among patients with ami complicated by cs who underwent va-ecmo. the study population was derived from the prospective institutional va-ecmo registry of samsung medical center in seoul, republic of korea from may to july (fig. ) . from this registry, ami patients complicated by cs were included in the analysis. ami was defined as evidence of myocardial injury (defined as an elevation of cardiac troponin values, with at least one value above the th-percentile upper-reference limit) with necrosis in a clinical setting, consistent with myocardial ischemia [ ] . cs was defined as persistent hypotension (systolic blood pressure < mmhg) for min or a state that required inotrope or vasopressor support to achieve a systolic blood pressure of more than mmhg despite adequate filling status, with signs of hypoperfusion [ ] . va-ecmo was applied to patients with medically refractory cs that did not respond to inotropes and vasopressors, or cardiac arrest that was not resuscitated with advanced cardiac life support [ , ] . patients who received va-ecmo due to stable angina, unstable angina, and variant angina were excluded from this study. patients, who were clinically stable before revascularization, but received va-ecmo for prophylactic purpose because of their poor cardiac function and high risk of expected treatment, were also excluded from the study. finally, patients were analyzed. as of the date the multidisciplinary ecmo team was founded at our institution, patients were classified into two groups: a pre-ecmo team group (before january , n = ) and a post-ecmo team group (after january , n = ). the institutional review board of samsung medical center approved this study, and written informed consent was obtained. our institution is a tertiary referral hospital with a tertiary-level intensive care unit. since the initiation of the use of ecmo in , the number of patients treated with ecmo had increased gradually. currently, more than patients are treated with ecmo each year at our institution. cardiac surgeons or interventional cardiologists inserted va-ecmo at bedside or in the catheterization laboratory. as far as there were no special indications, peripheral cannulation with percutaneous approach using the seldinger technique was chosen as the initial implant method. the capiox emergency bypass system (capiox ebs ™ ; terumo, inc., tokyo, japan) and permanent life support (pls; maquet, rastatt, germany) were used in our hospital. all patients received unfractionated heparin as an anticoagulant unless there was active bleeding. through our hospital's own protocol, the heparin infusion rate was adjusted to achieve the target activated clotting time of to s and activated partial thromboplastin time of to s, respectively. in the event of persistent pulmonary edema after ecmo initiation despite diuresis and inotropes, left ventricular decompression was achieved by either percutaneous atrial septostomy or surgical venting. in january , a multidisciplinary ecmo team was founded at our institution. our ecmo team consists of interventional cardiologists, critical care physicians, cardiovascular surgeons, heart failure physicians, a pharmacist, a nutritionist, and perfusionists who were formal intensive care registered nurses and received specific ecmo training. before the team's establishment, attending physician, who was capable of inserting and maintaining ecmo, was responsible for running ecmo. most of the ecmo-related decisions, from initiation to weaning, were made solely by the attending physician. instaff training was in charge of attending physician as well. no protocol existed for maintaining ecmo. only elective consultation to experienced cardiothoracic surgeons was possible in difficult clinical situations, with no -h on-call coverage by an ecmo specialist. however, after the foundation of the ecmo team, team members readily participated in the management of ecmo patients and all ecmo-related decisions, as described below. first, both the initiating and weaning of ecmo were performed under the supervision of the ecmo team. based on our institutional ecmo protocols for indications and contraindications (additional file : table s ), the ecmo team evaluated the eligibility of the patient for ecmo and made the final decision of whether to initiate ecmo or not. the decision of weaning was also made together by the attending physician and ecmo team based on our institutional weaning criteria. second, as part of daily rounds, echocardiography was performed to evaluate cardiac function and recovery. the pharmacist and nutritionist adjusted prescribed medications and nutritional plan in accordance with alterations of pharmacokinetics and metabolic status due to running ecmo and the critically ill status of the patient. also, the ecmo team checked the functional status of the ecmo device including the pump, oxygenator, and cannula daily, and assessed the occurrence of ecmo-related complications and the adequacy of relevant management. third, ecmo-trained physicians, cardiovascular surgeons, and perfusionists provided -h on-call coverage for ecmo patients and potential candidates. fourth, the ecmo team was responsible for staff training. doctors and nurses who were in charge of ecmo patients were educated by the ecmo team in order to properly manage patients according to their complicated clinical situations. fifth, a weekly meeting was held to discuss the issues of current ecmo patients as well as review previous cases for quality assurance. patient management was performed according to current standard guidelines [ , , , ] . the choice of treatment strategy of percutaneous coronary intervention (pci) (type, diameter, and length of stents; use of intravascular ultrasound; glycoprotein iib/iiia inhibitor use; and thrombus aspiration) was left to the discretion of the attending physicians. unless there was an undisputed reason for discontinuing dual-antiplatelet therapy, all patients were recommended to take aspirin indefinitely plus a p y inhibitor for at least year after the index procedure. coronary artery bypass graft (cabg) was performed using current standard methods. the left internal mammary artery was considered preferential for revascularization of the left anterior descending artery. patients who underwent cabg were recommended to take aspirin indefinitely. if intolerant to aspirin, taking clopidogrel as an alternative was also allowed. patients were prospectively registered at the time of index hospitalization. demographic feature and cardiovascular risk factor data were collected by detailed interview with patients or their families at admission. coronary angiographic findings and procedural history of pci, cabg, and ecmo were gathered during hospitalization. information about adjunctive therapies in addition to ecmo such as inotropes, mechanical ventilation, and continuous renal replacement therapy was collected at the time of discharge. follow-up outcomes were obtained from the review of patients' electronic medical records by research coordinators of the dedicated registry. clinical events that occurred within a -month follow-up period were analyzed. the primary outcome was in-hospital mortality. secondary outcomes included cardiac intensive care unit (cicu) mortality, -month all-cause death, -month readmission due to heart failure, successful weaning of ecmo, complications in the cicu, length of cicu stay, duration of ecmo, duration of mechanical ventilation, and duration of continuous renal replacement therapy. all clinical outcomes were defined according to the academic research consortium [ ] . all deaths were considered cardiac-related unless a definite non-cardiac cause could be established. successful weaning of ecmo was defined as maintaining hemodynamic stability after ecmo removal with or without getting durable left ventricular assist device or heart transplantation. included complications were major bleeding, vascular complications, infection, and limb ischemia. major bleeding was defined as bleeding in the brain, thorax, mediastinum, gastrointestinal tract, or abdomen or any fatal bleeding requiring transfusion or intervention. vascular complications included vessel perforation, arterial dissection, and site bleeding. site bleeding that was fatal was not included in vascular complications and included in major bleeding. minor complications such as local hematoma were not recorded in vascular complications. infection was defined as the presence of clinical symptoms or signs of infection with concurrent microbiological evidence of infection confirmed by blood culture during cicu stay. limb ischemia was defined as cases requiring surgical management or having dependent performance from to scale on functional ambulation classification resulting from limb ischemia at discharge [ ] . categorical variables were presented as numbers and relative frequencies and compared using the chi-square test or fisher's exact test, as appropriate. continuous variables were presented as mean ± standard deviation or median with interquartile range (q to q ) and compared using the student's t test or the wilcoxon rank-sum test, as appropriate. the risk of in-hospital mortality was compared using logistic regression analysis and was presented as odds ratios (or) and % confidence intervals (ci). to identify independent predictors of in-hospital mortality, multivariable logistic regression analysis was performed. variables were included in the analysis if they showed a significant relation in the univariate analysis with a p value of less than . and were considered clinically relevant. cumulative incidences of clinical outcomes were calculated by kaplan-meier estimates and compared using a log-rank test. cox proportional hazards regression analysis was performed to compare the risk of clinical events before and after the ecmo team establishment. risks of clinical events were presented with hazard ratios (hr) and % cis. all probability values were two-sided and p-values of less than . were considered statistically significant. statistical analyses were performed using the r statistical software (version . . ; r foundation for statistical computing, vienna, austria). baseline clinical and angiographic characteristics are shown in table . of the total patients, . % presented with st-segment elevation myocardial infarction (stemi), . % had out-of-hospital cardiac arrest, and . % had in-hospital cardiac arrest. as for angiographic profile, the left anterior descending artery and left main coronary artery accounted for . % and . % of the culprit vessels, respectively. a total of . % of patients presented with multivessel disease. nevertheless, there were no differences in baseline clinical and angiographic characteristics between the two groups, except for body mass index, previous history of myocardial infarction and pci, and baseline total bilirubin. also, indicators of severity in ecmo patients such as encourage score, ami-ecmo score, and sofa score were not different between the two groups. regarding treatment characteristics (table ) , successful revascularization through either pci or cabg was higher in the post-ecmo team group than in the pre-ecmo team group ( . % vs. . %; p = . ). in stemi patients, door-to-balloon time was shorter in the post-ecmo team group than in the pre-ecmo team group ( . vs. . , p = . ). extracorporeal cardiopulmonary resuscitation was performed in . % of study population and there was no significant difference in proportion between the two groups. arrest to ecmo pump-on time (for extracorporeal cpr patients only) and shock to ecmo pump-on time (for non-extracorporeal cpr patients only) were numerically shorter in the post-ecmo group than the pre-ecmo group, with no statistical significance. for supplementary treatments after ecmo insertion, the use of inotropes or vasopressors, intra-aortic balloon pump, and mechanical ventilation was significantly lower, whereas distal perfusion was more frequently performed in the post-ecmo team group than in the pre-ecmo team group. clinical outcomes are presented in table . in-hospital mortality occurred in patients ( . %) and cicu mortality occurred in patients ( . %). in-hospital mortality ( . % vs. . %; p = . ) and cicu mortality ( . % vs. . %; p = . ) were significantly lower in the post-ecmo team group than in the pre-ecmo team group (fig. ) . the lower rate of in-hospital mortality in the post-ecmo team group was mainly driven by the lower rate of cardiovascular death ( . % vs. . %; p = . ). however, there were no significant differences between the two groups regarding non-cardiovascular death ( . % vs. . %; p > . ). clinical outcomes at months of follow-up showed consistent findings in relation with the primary outcome (fig. ) . the multidisciplinary team approach was associated with significantly lower risk of all-cause death ( . % vs. . %; hr: . , % ci . - . ; p < . ) and readmission due to heart failure ( . % vs. . %; hr: . , % ci . - . ; p = . ) at months of follow-up. regarding the management of va-ecmo patients in the cicu, specific parameters are compared in table and additional file : table s . the successful weaning of va-ecmo ( . % vs. . %; p = . ) was higher in the post-ecmo team group than in the pre-ecmo team group. however, the length of cicu stay did not differ significantly between the two groups. also, the duration of ecmo, mechanical ventilation, and continuous renal replacement therapy were longer in the post-ecmo team group than in the pre-ecmo team group. as for complications (i.e., major bleeding, vascular complication, infection, limb ischemia), each component tended to be lower in the post-ecmo team group than in the pre-ecmo team group, resulting in a statistically significant decrease in overall complications in the post-ecmo team group ( . % vs. . %; p = . ). age, out-of-hospital cardiac arrest, successful revascularization, use of mechanical ventilation, use of continuous renal replacement therapy, annual ecmo volume and the multidisciplinary ecmo team approach showed significant relation in the univariable analysis and were included in multivariable logistic regression model (table ). in this model, the multidisciplinary ecmo team approach was associated with decreased risk of in-hospital mortality (adjusted or: . , % ci . - . ; p = . ). the current study is the first to evaluate the impact of a multidisciplinary ecmo team approach on clinical outcomes in ami patients complicated by cs using data from a prospective va-ecmo registry. the main findings were as follows. first, in-hospital mortality and cicu mortality were significantly lower in the post-ecmo team group than in the pre-ecmo team group. second, the risks of all-cause death and readmission due to heart failure at -month follow-up were also significantly lower in the post-ecmo team group than in the pre-ecmo team group. third, in a multivariable logistic regression model, multidisciplinary team approach was associated with decreased risk of in-hospital mortality in ami patients with cs undergoing va-ecmo. although multidisciplinary team approach has been recommended in the care of critically ill patients, only a few studies to date have addressed its effects on clinical outcomes [ , ] . also, even though the american heart association recommended that patients with cs be managed by a multidisciplinary team [ ] , nonetheless, this recommendation was primarily based on expert opinions and research regarding the association of hospital volume with clinical outcomes in cs patients, not the multidisciplinary approach [ , ] . furthermore, considering that inserting ecmo is a high-risk intervention and maintaining ecmo requires highly sophisticated measures, the extracorporeal life support organization guidelines recommended that ecmo be operated by multidisciplinary team including trained specialists [ ] . however, there are no data about the relationship between multidisciplinary care and clinical outcomes in ami patients complicated by cs undergoing va-ecmo. therefore, we aimed to investigate the impact of multidisciplinary approach in this setting and demonstrated its beneficial effect, including reduction in mortality. our study has several strengths. a large number of patients were observed for a sufficient follow-up period of months considering that the study population was extremely severely ill patients with cs. also, mortality as well as various treatment strategies and secondary outcomes were compared before and after the introduction of the multidisciplinary ecmo team. lastly, the study population was extracted from a large prospective registry of a tertiary university hospital that reflects the real-world population and practices. the in-hospital mortality in our study before multidisciplinary team introduction was . %, similar to that of other multicenter studies ( - %) [ , ] . therefore, our study suggested that, in addition to contemporary practice of cs, the additional benefit of a multidisciplinary approach might exist. the reasons how the multidisciplinary approach improved clinical outcomes are multifactorial in the current study. first, the multidisciplinary team consisted of experts from diverse fields. thereby, the multidisciplinary approach enabled critically ill cs patients to receive systematic care and at the same time appropriate treatment for each problem. as a team leader, the critical care physician was closely involved and coordinated the multidisciplinary approach in order to properly manage multifaceted acute critical care [ ] . heart failure physicians were also involved in the treatment from the beginning of the initial state of shock and contributed to improve mortality not only by providing acute heart failure care, but also by maintaining the patient's long-term cardiac function and stably directing the process toward implementing exit strategies such as ventricular assist devices and heart transplantation for indicated patients [ ] . furthermore, a pharmacist and nutritionist were included in the multidisciplinary team. the adjustment of medications according to the altered pharmacokinetics of ecmo patients led to the maintenance of drugs at the appropriate therapeutic levels without side effects [ , ] . likewise, customizing nutritional delivery according to table predictors of in-hospital mortality c-statistic of the logistic regression model for in-hospital mortality was . ( % ci . - . ) entered variables in univariate analysis for evaluating significant relation with the primary outcome included multidisciplinary approach, age, male, body mass index, hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, history of myocardial infarction, history of percutaneous coronary intervention, history of cerebrovascular accident, st-segment elevation myocardial infarction, out-of-hospital cardiac arrest, left ventricular ejection fraction, laboratory findings in table , anterior infarction, multivessel disease, percutaneous coronary intervention, coronary artery bypass graft, extracorporeal cardiopulmonary resuscitation, insertion of ecmo before revascularization, distal perfusion, use of inotropes or vasopressors, use of intra-aortic balloon pump, use of mechanical ventilation, use of continuous renal replacement therapy, overall complications and annual ecmo volume ci confidence interval, ecmo extracorporeal membrane oxygenation, or odds ratio [ , ] . second, our institutional maintenance strategies of ecmo patients were changed in order to reduce ischemic time after multidisciplinary team implantation. if cardiopulmonary resuscitation (cpr) persisted for longer than min without the return of spontaneous circulation, the ecmo team was activated and extracorporeal cpr was immediately started, unless a patient was contraindicated to receive ecmo. also at least one primed ecmo circuit was always prepared in advance at our institution. as a result, in stemi patients, doorto-balloon time was significantly shorter in the post-ecmo group than in the pre-ecmo group. also arrest to ecmo pump-on time and shock to ecmo pump-on time showed shorter tendency in the post-ecmo team group than in the pre-ecmo team group. third, various efforts were made to reduce ecmorelated complications. during daily rounds, evaluation of cardiac function through echocardiography and modifications of clinical settings were made in order to maintain appropriate hemodynamic status. these efforts have contributed to prevent organ damage due to ischemia or overperfusion. also, multidisciplinary team assessed the risk of ecmo-related complications by checking physical examinations and related laboratory results on a daily basis. in addition, as one of the changes in our institution's ecmo maintenance strategies, awake ecmo was pursued unless pulmonary gas exchange was insufficient to cause upper body hypoxia. in our study, the use of mechanical ventilation was significantly lower in the post-ecmo team group and this may have played an important role in avoiding complications related to mechanical ventilation and sedation [ ] . lastly, mandatory distal perfusion, which was reported to reduce limb ischemia and even improve `survival [ ] , was strongly recommended. as a result, all of these diverse efforts significantly reduced the incidence of complications after the team establishment, which was considerably lower than the values shown in other studies [ ] . as limitations, first, this study was an observational, prospective registry based, single-center study. consequently, the influence of confounding bias or selection bias affecting the results of the research cannot be excluded. although multivariable adjusted analysis was performed by adding various variables, the effects of confounding variables, such as annual ecmo volume or the learning curve of ecmo, were not completely corrected. therefore, the results may be influenced by multifactorial causes other than multidisciplinary team. furthermore, there might be concern about differences between the two groups when selecting patients who were appropriate candidates for using va-ecmo. however, considering that selecting appropriate patient with team-based and protocolized decision is the effect of the multidisciplinary team, this can be considered as one of benefit of multidisciplinary team rather than the selection bias. second, the advances in the treatment of shock patients or accumulation of experiences over time may have served as potential bias in the study. during the study period, three major randomized trials in ami patients by cs were done [ , , ] . first two studies were conducted to investigate the prognostic implications of immediate multivessel pci and iabp, respectively, and showed no significant difference in mortality [ , ] . on the other hand, subgroup analysis of the other study, that compared the effects of vasopressors in patients with cs, showed survival benefit of norepinephrine over dopamine [ ] . these advancements seemed to have played some role in improving the clinical results. however, as shown in fig. , when the patients who were treated before the multidisciplinary team establishment ( - ) were divided into two groups according to time, there was no significant difference in clinical outcomes between the two groups. on the other hand, there was a significant improvement in mortality between before and after . considering there was no major change in patient management other than the foundation of the multidisciplinary team, this improvement could be regarded as an additional benefit of multidisciplinary approach on the top of other advances in practice strategy or the accumulation of experiences. third, our data could not show in detail how multidisciplinary approach affected mediating outcomes and which mediating outcomes were improved, that led to decreased mortality. this is a limitation of our retrospective study, in which data were insufficiently investigated. further thoroughly investigated prospective study is needed to elucidate the detailed influence of multidisciplinary approach. fourth, the multidisciplinary approach did not show a significant reduction in the duration of cicu stay and adjunctive treatment. nonetheless, the interpretation of this result should be done with caution. this result might be related with the ability of multidisciplinary team to maintain patients stable in the long-term and save those who may have died previously. as a result, the multidisciplinary approach inevitably increased the duration of organ support. a multidisciplinary approach was associated with significantly lower in-hospital mortality in ami patients complicated by cs who underwent va-ecmo. therefore, our findings support the current expert consensus that a multidisciplinary ecmo team is indispensable for improving outcomes in ami patients with cs. early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction intraaortic balloon support for myocardial infarction with cardiogenic shock emergency circulatory support in refractory cardiogenic shock patients in remote institutions: a pilot study (the cardiac-rescue program) predicting survival after ecmo for refractory cardiogenic shock: the survival after veno-arterial-ecmo (save)-score accf/aha guideline for the management of st-elevation myocardial infarction: a report of the american college of cardiology foundation/american heart association task force on practice guidelines esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with st-segment elevation of the european society of cardiology (esc) a team-based approach to patients in cardiogenic shock contemporary management of cardiogenic shock: a scientific statement from the american heart association venoarterial extracorporeal membrane oxygenation in cardiogenic shock left ventricular unloading during extracorporeal membrane oxygenation: insights from meta-analyzed observational data corrected for confounders nosocomial infections in adult cardiogenic shock patients supported by venoarterial extracorporeal membrane oxygenation bleeding, transfusion, and mortality on extracorporeal life support: ecls working group on thrombosis and hemostasis neurologic complications of extracorporeal membrane oxygenation: a review position paper for the organization of ecmo programs for cardiac failure in adults extracorporeal life support organization registry international report accf/aha guideline for coronary artery bypass graft surgery: a report of the american college of cardiology foundation/american heart association task force on practice guidelines esc guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the european society of cardiology (esc) standardized end point definitions for coronary intervention trials: the academic research consortium- consensus document magliozzi mr gait assessment for neurologically impaired patients. standards for outcome assessment kahn jm the effect of multidisciplinary care teams on intensive care unit mortality multidisciplinary critical care and intensivist staffing: results of a statewide survey and association with mortality effect of cardiogenic shock hospital volume on mortality in patients with cardiogenic shock the encourage mortality risk score and analysis of long-term outcomes after va-ecmo for acute myocardial infarction with cardiogenic shock association between presence of a cardiac intensivist and mortality in an adult cardiac care unit outcomes of patients with acute decompensated heart failure managed by cardiologists versus noncardiologists pharmacist participation on physician rounds and adverse drug events in the intensive care unit trough concentrations of vancomycin in patients undergoing extracorporeal membrane oxygenation adequacy of nutrition support during extracorporeal membrane oxygenation evolution of critical care cardiology: transformation of the cardiovascular intensive care unit and the emerging need for new medical staffing and training models: a scientific statement from the american heart association awake" extracorporeal membrane oxygenation (ecmo): pathophysiology, technical considerations, and clinical pioneering fluoroscopyguided simultaneous distal perfusion as a preventive strategy of limb ischemia in patients undergoing extracorporeal membrane oxygenation comparison of dopamine and norepinephrine in the treatment of shock one-year outcomes after pci strategies in cardiogenic shock publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : table s . indications and contraindications for va-ecmo deployment. table s . duration of organ support and cicu stay. ami: acute myocardial infarction; cabg: coronary artery bypass graft; cicu: cardiac intensive care unit; cpr: cardiopulmonary resuscitation; cs: cardiogenic shock; ecmo: extracorporeal membrane oxygenation; pci: percutaneous coronary intervention; stemi: st-segment elevation myocardial infarction; va: veno-arterial. key: cord- -ygocpnht authors: de jager, pauline; kneyber, martin c. j. title: response to the authors date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: ygocpnht nan we like to thank the authors for their interest in our manuscript and their positive feedback. high-frequency oscillatory ventilation (hfov) is used in our unit for any type of pards when the patient meets specific criteria as outlined in our manuscript (in summary, peak inspiratory pressure [pip] > - cm h o, peep > cm h o, fio > . , and oxygenation index [oi] increases on three consecutive -h measurements despite increasing peep) [ ] . we understand the author's perspective that hfov might be more effective in certain types of pards, but we advocate that hfov should not only be considered in case of refractory hypoxaemia, but also when the bedside team wants to prevent ventilator settings becoming toxic. an individualised lung volume optimisation manoeuvre (such as the staircase incremental-decremental titration of the continuous distending pressure (cdp) helps in identifying patients who have potential for lung recruitability since the response is highly heterogeneous among pards [ ] . as our data showed, such an individualised manoeuvre can be tolerated well in terms of haemodynamic effects with a minimal risk of barotrauma (in fact, we observed no barotraumas following the manoeuvre in our cohort). the authors raise an important point: what is the "optimal" frequency in relation to pards severity? although the concept of the corner frequency is quite clear, it is difficult to detect at the bedside how the "optimal" frequency can be identified in heterogenous pards [ ] . basically, the lower the lung compliance, the higher the frequency probably should be. for simplicity, when we implemented the hfov clinical algorithm in our unit, the advice was to start with hz in all patients, irrespective of age or pards severity and titrate immediately after the lung volume optimisation manoeuvre using the pco to give direction (e.g. frequency up or down). our data confirmed that it was possible to do this in all patients, irrespective of age (fig. ) . we agree that in a subgroup of patients in our cohort, especially those with mild-to-moderate pards optimisation of conventional mechanical ventilation settings might have been attempted. the median oi of as pointed out by the reviewer is the oi after the lung volume optimisation manoeuvre, hence the high cdp we use as part of the open-lung concept confounds the oi. it is true that in general in the paediatric intensive care unit there is a relatively low use of positive end-expiratory pressure (peep) and tolerance of high fio instead. however, the best strategy to optimise cmv in children with severe pards remains uncertain [ ] . to date, there is no specific peep strategy shown to be beneficial nor are there outcome data demonstrating that higher peep is better than lower peep in pards, although there are some suggestions that lower peep in pards may be associated with increased mortality [ ] . we also do not know what the optimal vt is in (severe) pards [ ] . hence, we advocate that hfov should also be considered if the bedside team wants to prevent ventilator settings becoming toxic. we eagerly await the results of a -by- factorial randomised controlled trial comparing the effects of ventilation strategy (cmv vs hfov) with or without prone positioning (http://www.prosp ect-netwo rk.org) on patient outcome [ ] . feasibility of an alternative, physiologic, individualized openlung approach to high-frequency oscillatory ventilation in children lung volume optimization maneuver responses in pediatric high frequency oscillatory ventilation understanding the pressure cost of ventilation: why does high-frequency ventilation work? recommendations for mechanical ventilation of critically ill children from the paediatric mechanical ventilation consensus conference (pemvecc) peep lower than the ards network protocol is associated with higher pediatric ards mortality tidal volume and mortality in mechanically ventilated children: a systematic review and meta-analysis of observational studies* high-frequency oscillatory ventilation for pards: awaiting prospect not applicable. authors' contributions mk drafted the manuscript. pdj contributed to the intellectual content of the manuscript. both authors read and approved the final manuscript. none. key: cord- -dlwph za authors: alshahrani, mohammed s.; sindi, anees; alshamsi, fayez; al-omari, awad; el tahan, mohamed; alahmadi, bayan; zein, ahmed; khatani, naif; al-hameed, fahad; alamri, sultan; abdelzaher, mohammed; alghamdi, amenah; alfousan, faisal; tash, adel; tashkandi, wail; alraddadi, rajaa; lewis, kim; badawee, mohammed; arabi, yaseen m.; fan, eddy; alhazzani, waleed title: extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus date: - - journal: ann intensive care doi: . /s - - -x sha: doc_id: cord_uid: dlwph za background: middle east respiratory syndrome (mers) is caused by a coronavirus (mers‐cov) and is characterized by hypoxemic respiratory failure. the objective of this study is to compare the outcomes of mers-cov patients before and after the availability of extracorporeal membrane oxygenation (ecmo) as a rescue therapy in severely hypoxemic patients who failed conventional strategies. methods: we collected data retrospectively on mers-cov patients with refractory respiratory failure from april to december in intensive care units (icus) in saudi arabia. patients were classified into two groups: ecmo versus conventional therapy. our primary outcome was in-hospital mortality; secondary outcomes included icu and hospital length of stay. results: thirty-five patients were included; received ecmo and received conventional therapy. both groups had similar baseline characteristics. the ecmo group had lower in-hospital mortality ( vs. %, p = . ), longer icu stay (median vs. days, respectively, p < . ), and similar hospital stay (median vs. days, p = . ). in addition, patients in the ecmo group had better pao /fio at days and of admission to the icu ( vs. , and vs. , p < . ), and less use of norepinephrine at days and ( vs. %; and vs. %, p < . ). conclusions: ecmo use, as a rescue therapy, was associated with lower mortality in mers patients with refractory hypoxemia. the results of this, largest to date, support the use of ecmo as a rescue therapy in patients with severe mers-cov. middle east respiratory syndrome (mers), which was first described in , is caused by a novel coronavirus (mers-cov). the world health organization (who) as of december reported confirmed cases of the mers-cov infection globally with an overall mortality rate of % [ ] . the majority of cases were reported in saudi arabia, wherein were confirmed cases, and of which ( %) died [ ] . human coronaviruses were first identified in the mid- s and usually cause mild upper-respiratory tract illness. in , the first confirmed case of mers-cov was reported from saudi arabia [ ] . mers-cov infection is associated with significant mortality related to the virulence of the virus, nature of the disease, and the lack of effective therapy. patients with mers-cov who develop acute respiratory distress syndrome (ards) are at a high risk of dying from refractory hypoxemia, multiorgan failure, and septic shock [ ] . current interventions such as lung protective ventilation, prone ventilation, and neuromuscular blocking agents have been shown in randomized trials to improve mortality in patients with ards [ ] [ ] [ ] . however, in some patients, these conventional measures fail to maintain adequate oxygenation; therefore, other rescue therapies are considered, such as different modes of ventilation, inhaled pulmonary vasodilators, and extracorporeal membrane oxygenation (ecmo). anticipated difficulties in patient recruitment, study design, and ethical concerns affect the feasibility of conducting randomized clinical trials that examine the efficacy of ecmo in this population. therefore, observational studies are a reasonable alternative. in this study, we aim to describe the effect of ecmo rescue therapy on patient-important outcomes in patients with severe mers-cov. in response to the large mers-cov outbreak, the saudi ministry of health implemented a national ecmo program in april . the saudi ecmo program provided a rapid transportation chain system (medevac system), isolated intensive care unit (icu) beds, and venovenous (v-v) ecmo machines in selected centers across the country. an ecmo team was created that was available h a day/ days a week. the team included an intensivist trained in ecmo, a cardiac surgeon, a perfusionist, and ecmo-trained nurses. the intensivist on the ecmo team triaged all calls from other centers based on predefined criteria, wherein patients were predetermined to be candidates to receive ecmo or not. criteria for eligibility to receive ecmo were based on the extracorporeal life support organization (elso) [ ] guidelines and are listed below. we retrospectively identified patients who would have been eligible for ecmo but did not receive it because the ecmo program was not available at that time (prior to april ). the intervention (ecmo) group was included from five main ecmo centers in three major cities in saudi arabia after the program initiation (april to december ). all participating hospitals were accredited by the joint commission international and had closed icus with -h coverage by trained intensivists. we obtained ethics approval from the saudi ministry of health ethics review board and from individual centers' ethics boards. patients were candidates to receive ecmo if they have met the following criteria: the ecmo group included patients who met the above criteria and received ecmo after implementing the ecmo program from april to december . we included all patients with mers-cov who received ecmo during that period. the control group were patients who met the above criteria but did not receive ecmo in the period prior to the introduction of ecmo program (prior to april ). weaning from ecmo was primarily based on clinical improvement demonstrated by adequate oxygenation and gas exchange shown in vital signs, blood gases, and chest x-ray. the decision for readiness of a patient to be weaned from ecmo was left to the judgment of treating clinician and the ecmo team. the weaning process followed the elso criteria as follow: weaning starts by decreasing the flow to l/min while keeping the sweep of % (to maintain spo > %). if spo remains within target, a trial of clamping the catheters and keeping the patient on the ventilator at appropriate settings was attempted. we designed an electronic pretested data abstraction forms; the forms were pilot tested prior to data collection to ensure accuracy and reproducibility. trained personnel collected the data at each participating center under the supervision of the local principal investigators. research personnel collected data on patients' demographics, comorbidities, acute physiology and chronic health evaluation ii (apache ii) score, laboratory results (hemoglobin concentration, white blood and platelets counts, kidney function, blood gases), ventilator modes and settings, interventions used to treat refractory hypoxemia (prone ventilation, use of neuromuscular blocking drugs, and pulmonary vasodilators), vasoactive support, antimicrobial and antiviral therapy, steroid use, and primary and secondary outcome data. data were tested for normality using the kolmogorov-smirnov test. a repeated-measures analysis of variance was performed. fischer's exact test was used for the categorical data. independent t test was used to compare the continuous variables in the two groups. the mann-whitney u test was performed to compare the nonparametric values of the two groups. data were expressed as median (interquartile range (iqr) [range]), number (proportion), or mean (sd) as appropriate. the volume of cases was not enough to allow a priori power analysis. however, a post hoc power analysis indicated that the current sample size of patients is powered to detect % absolute difference in mortality rate, with a type i error of . and a power of %. a value of p < . was considered statistically significant. eighty patients with confirmed mers-cov infection were admitted to the icus of participating centers from april to december . thirty-five patients met our eligibility criteria and were included in the analysis, in the ecmo group and in the control group. as shown in table , the baseline characteristics were similar in both groups; the median ages were ( vs. years), and mean apache ii score ( vs. ) were not statistically different. (p = . and p = . ; respectively). adjunctive therapies were used in both groups. ribavirin was used significantly more often in the ecmo group compared to the control group ( vs. %, p = . ), interferon was also used more in the ecmo cohort compared to controls ( vs. %, p = . ), and the use of steroids was similar in both groups ( vs. %, p = . ). at day one of eligibility to ecmo, more patients in the control group required hemodynamic support with norepinephrine compared to ecmo group; however, both groups had similar use of epinephrine and dobutamine, continuous renal replacement therapy (crrt), modes of ventilation, positive end-expiratory pressure (peep), and neuromuscular blocking agents (tables and ). alveolar recruitment maneuver was used in one patient in the ecmo group. none of the patients received prone ventilation. throughout days - , more patients in the control group developed renal impairment and had significantly lower pao /fio ratio (table ) . other laboratory values were similar between both groups (table ). however, due to the small sample size, it was not feasible to adjust for all confounding factors. in the ecmo group, the v-v mode was used in all patients via the percutaneous cannulation approach for vascular access. femoral-femoral access was used in % of patients, while femoral-jugular access was used in % of cases. ecmo access was inserted by a cardiac surgeon in % of cases and by a cardiac intensivist in the remaining %. chest x-ray was used to confirm successful cannulation in patients and transesophageal echocardiography (tee) in one patient. blood flow (l min − ), revolutions per minute, and sweep gas among ecmo patients had a mean (sd) of . ( . ), . ecmo-related mechanical complications occurred in ( %) patients; one patient developed pneumothorax that was treated with chest tube insertion, and two patients had major bleeding immediately after the initiation of ecmo. compared to the control group, the ecmo group had significantly lower in-hospital mortality ( vs. %; p = . ), longer icu stay ( vs. days; p = . ) ( table and fig. ). less use of norepinephrine at days and (p < . ), and better oxygenation (higher pao / fio ratio) throughout days - (table ). in this retrospective cohort study, we found that ecmo rescue therapy was associated with lower in-hospital mortality, better oxygenation, and fewer organ failures compared to historical control (usual care) in patients with severe mers-cov. however, the length of hospital stay was the same and a possible explanation is that during the crisis phase, patients were mechanically ventilated in the ward when icu beds are full, and it is possible that this could have contributed to similar stay in hospital in both groups. although elso issued guidelines on the use of ecmo in patients with ards, these guidelines do not address specific disease context, and are difficult to generalize to the heterogeneous ards population. therefore, we conducted this observational study to report on the efficacy and safety of ecmo in patients with severe mers-cov infection. there is a single case report in the literature looking at ecmo in mers-cov patients. guery et al. described the use of ecmo in two patients with acute respiratory failure secondary to mers-cov infection in france, where both patients developed severe hypoxia and increasing oxygen requirements, leading to mechanical ventilation and ecmo use. one patient died, and the other survived after approximately months in hospital [ ] . ecmo use in respiratory failure has been reported with variable survival rates. the first randomized clinical trials (rcts) failed to prove superiority of ecmo over conventional management [ , ] . however, the severe adult respiratory failure (cesar) trial showed improved -month survival in patients who were referred early to an ecmo center [ ] . this was the largest clinical trial to investigate the efficacy of early use ecmo in patients with ards. despite concerns about the trial design and possible differences in steroid use and ventilator strategies, these results contributed to the increasing use of ecmo worldwide. in this study, we observed no significant differences in the use of adjunctive therapies except for ribavirin use in the ecmo group. the benefit of antiviral therapy in mers-cov infection remains unclear. recent korean guidelines published during the mers-cov outbreak in south korea suggested the use of antiviral therapy in patients with severe mers-cov [ ] . in patients with respiratory failure from h n infection who required the use of ecmo, the survival rate varied considerably between studies ranging from to % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . there was a large variation in survival rates, which could be explained by differences in patients' baseline characteristics and severity of illness. in one study, older, obese, diabetic, or immunocompromised patients were found to be at a higher risk of developing severe [ ] [ ] [ ] [ ] . in this study, the two groups were comparable at baseline, and there were no significant differences between groups in any of these variables. another large observational study examined the predictors of death in h n patients who underwent v-v ecmo and found that creatinine and bilirubin levels, systemic arterial pressure, hematocrit, and pre-ecmo hospital length of stay were associated with higher mortality [ ] . another important factor is the center experience and volume of cases; this could have contributed to the variability in survival rates with ecmo use. a recent study by barbaro et al. [ ] demonstrated that centers with > ecmo cases/year had better survival rates than centers with less than cases per year. in saudi arabia, ecmo was not available except in one center until the mers-cov crisis; thereafter, the ecmo program was implemented as a therapeutic option for patients with refractory hypoxemia. ecmo interventions were run in tertiary centers with equipped icus by most experienced intensivists and perfusionists who received training in ecmo prior to the start of the program. although more ecmo patients received ribavirin and interferon therapy, we do not believe that this difference has an impact to our findings. published reports on this therapy are limited, but none showed significant improvement with this combination [ ] [ ] [ ] . the largest study to date published in abstract format [ ] showed no reduction in mortality. therefore, we believe that the imbalance of co-interventions between the two groups is unlikely to affect the estimation of treatment effect. in regard to infection control issues, caregivers safety of ecmo patients was organized and maintained by aggressive measures which were applied strictly and monitored closely with all admissions were taken to airborne isolated rooms which impacted the containment of the virus plus applying the universal protective personal measures all the time during the patients encounter. because of these stringent measures, there were no reports by or about any caregiver of any ecmo patient being affected. to our knowledge, this is the largest study to describe outcomes in patients with mers-cov who received ecmo. there are several strengths to our study: the "before and after" design allowed us to compare ecmo cases to a control group with similar demographics and within the same institutions. we also collected data on important variables and confounders, and conducted adjusted analyses to assess the impact on the results. we adhered to the strengthening the reporting of observational studies in epidemiology (strobe) guidelines [ ] . despite the strengths of our study, it has several important limitations. first, the retrospective nature of this study renders it at risk of bias. all patients in the control group died, which may be explained by the severity of illness, as these were patients who had ards and were eligible otherwise. we cannot rule out the possibility of selection bias, as we were unable to track all transfer requests due to the outbreak and crisis at the time, leaving us with limited information. in addition, some patients were transferred from non-participating ecmo centers; therefore, baseline pre-ecmo data such as blood gases and ventilator settings could not be obtained. furthermore, due to insufficient documentation during the outbreak and crisis circumstances, we were not able to track the ecmo requests to the referral call center. there were differences in some co-interventions (e.g., antiviral therapy), and the influence of unmeasured confounders cannot be excluded. such concerns can only be addressed in rcts; however, conducting rct is likely to be challenging in the context of epidemics. this study was not designed to compare the cost of interventions; although it is an important outcome that could help the clinicians and stakeholders to make decisions. lastly, the small sample size limited our ability to perform an adequate multivariate analysis. similar to other ecmo studies, it is difficult to determine if the mortality was the result of refractory respiratory failure or other causes like septic shock or other organs failure. in summary, the use of ecmo was associated with lower mortality in patients with severe mers-cov infection and refractory hypoxia. future randomized trials, although challenging to conduct, are highly needed to confirm or dispute these observations. until more data are available, ecmo could be considered as a rescue therapy in selected mers-cov patients with refractory hypoxemia. 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ribavirin and interferon alfa- a for severe middle east respiratory syndrome coronavirus infection: a retrospective cohort study ifn-α a or ifn-β a in combination with ribavirin to treat middle east respiratory syndrome coronavirus pneumonia: a retrospective study effect of ribavirin and interferon on the outcome of critically ill patients with mers the strengthening the reporting of observational studies in epidemiology (strobe) statement: guidelines for reporting observational studies we wish to acknowledge the saudi ministry of health for implementing a national ecmo program in april who assisted us throughout the course of this research. we thank our colleagues from all participating icus throughout saudi arabia who provided insight and expertise that greatly assisted the research, and for their comments on an earlier version of the manuscript. the authors declare that they have no competing interests. all data produced and analyzed during this study are included and presented as tables in this manuscript. authors have no objection in granting and assigning the annals of intensive care journal unrestricted right to reproduce, publish, and distribute this manuscript in all forms including electronic form either offline or online media. no patients were involved neither in the design, recruitment, and conduction of this study nor in the development of outcome measures. we plan to disseminate the results of the study in lay language for patient interest groups. we had one institutional review board approval (irb-h- -j- ) for the ecmo from the saudi arabia ministry of health as all ecmo program during the outbreak was under the umbrella of the ministry. all authors declare that they receive no support from any commercial organization or company. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -w aa elj authors: tonetti, tommaso; grasselli, giacomo; zanella, alberto; pizzilli, giacinto; fumagalli, roberto; piva, simone; lorini, luca; iotti, giorgio; foti, giuseppe; colombo, sergio; vivona, luigi; rossi, sandra; girardis, massimo; agnoletti, vanni; campagna, anselmo; gordini, giovanni; navalesi, paolo; boscolo, annalisa; graziano, alessandro; valeri, ilaria; vianello, andrea; cereda, danilo; filippini, claudia; cecconi, maurizio; locatelli, franco; bartoletti, michele; giannella, maddalena; viale, pierluigi; antonelli, massimo; nava, stefano; pesenti, antonio; ranieri, v. marco title: use of critical care resources during the first weeks (february –march , ) of the covid- outbreak in italy date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: w aa elj background: a covid- outbreak developed in lombardy, veneto and emilia-romagna (italy) at the end of february . fear of an imminent saturation of available icu beds generated the notion that rationing of intensive care resources could have been necessary. results: in order to evaluate the impact of covid- on the icu capacity to manage critically ill patients, we performed a retrospective analysis of the first weeks of the outbreak (february –march ). data were collected from regional registries and from a case report form sent to participating sites. icu beds increased from to ( . %), and patients receiving respiratory support outside the icu increased from ( . %) to ( . %). patients receiving respiratory support outside the icu were significantly older [ vs. years], had more cerebrovascular ( . vs. . %) and renal ( . vs. . %) comorbidities and less obesity ( . vs. . %) than patients admitted to the icu. pao( )/fio( ) ratio, respiratory rate and arterial ph were higher [ vs. ; vs. breath/min; . vs. . ] and paco( ) and base excess were lower [ vs. mmhg; . vs. . ] in patients receiving respiratory support outside the icu than in patients admitted to the icu, respectively. conclusions: increase in icu beds and use of out-of-icu respiratory support allowed effective management of the first days of the covid- outbreak, avoiding resource rationing. data regarding the impact of covid- outbreak on the capacity of the health-care system to accomplish the need for icu care are limited. the estimated need for intensive care unit (icu) admission is variable, ranging between . [ ] , . [ ] and . % [ ] . reported icu mortality ranges between [ ] , [ ] [ ] , and % [ ] . this extreme variability has been attributed to differences in terms of beds availability, staff and organization of intensive care units [ ] . on thursday, th february , the first cases of positivity for sars-cov- were recorded in lombardy region, northern italy. since then, the number of patients with corona virus and acute hypoxemic respiratory failure in three regions of northern italy (lombardy, veneto and emilia-romagna) dramatically increased, subsequently leading to the call of a national emergency status [ ] . a mathematical model of the occupation of intensive care resources in italy predicted the saturation of the theoretical availability of beds on the national territory by mid-april [ ] . in order to respond to such predicted growing need for icu resources, on march st the italian government published a notice, ordering to increase the number of icu beds (https ://www.salut e.gov.it/porta le/homem obile .jsp) and approved a law decree that allocated million euros to the public health service to bring the number of icu beds for invasive mechanical ventilation to the % of the total hospital beds (https :// www.gazze ttauf ficia le.it/eli/id/ / / / g / sg). since the spread of the sars-cov- virus is growing and critical care resources of public health systems are dramatically challenged [ ] , we reasoned that a better understanding of clinical management and icu requirements for patients with severe covid- at the very beginning of the outbreak may support resources planning and may help to set effective organizational and clinical interventions for the most seriously affected patients. the objective of the study was therefore to ( ) describe the process of expansion of the icu capacity in response to the covid- outbreak during the first weeks of the pandemics; ( ) describe settings and modalities of care of acutely ill covid- patients; ( ) compare outcomes between critically ill patients with covid- receiving care in or outside the icu. we retrospectively studied consecutive critically ill patients with confirmed covid- who were referred to the hospitals of the lombardy, veneto and emilia-romagna regions during the first weeks of the italian outbreak (february - march , ) . a confirmed case of covid- was defined as a patient with a positive result on high-throughput sequencing or real-time reverse transcriptase-polymerase chain reaction assay of nasal and pharyngeal swab specimens [ ] . in total, hospitals ( in lombardy, in emilia-romagna and in veneto) participated in the study. institutional review boards reviewed the protocol and authorized data collection. data on icu beds expansion and on total hospital and icu admissions were gathered from registries of the regional icus coordinators of lombardy (ap), veneto (pn) and emilia-romagna (vmr) [ ] . moreover, a data collection form was circulated among participating icus and de-identified data on patients admitted in the icu and receiving respiratory support outside the icu were recorded h after admission. in particular, demographics, comorbidities and basic physiological data were collected. in the initial days of the epidemics in northern italy, icu beds and personnel were made available by closing elective surgical admissions and centralizing to a limited number of single non-covid- hub hospitals all neuro-and cardiac-surgical admissions. moreover, ordinary availability of icu beds in the three regions was increased from to ( . %); in particular, icu capacity increased by . % (from to ), . % (from to ) and . % (from to ) in lombardy, emilia-romagna and veneto, respectively. this was achieved by converting operating rooms, coronary units, step-down units and recovery rooms to fully equipped covid- icus. furthermore, the use of outof-icu respiratory support in the form of cpap or niv [ ] [ ] [ ] was extended to many different wards, although initial reports suggested caution in the use of non-invasive respiratory support in covid- patients due to the risk of transmission of infection [ ] . all patients included in the study underwent evaluation by a senior intensivist, who decided according to her/ his clinical judgment and to local protocols whether to treat the patient in a ward under supervision of the icu team or to admit the patient to the icu. the criteria for icu admission were: (a) failure of noninvasive respiratory support, defined as persistent hypoxemia, tachypnea and respiratory distress or development of hypercapnia despite the application of cpap/niv; (b) expected imminent need for invasive mechanical ventilation; (c) absence of a do-not-intubate order, as discussed collegially by the intensivist and the ward staff physicians caring for the patient. at all sites out-of-icu respiratory support was provided by care teams that included at least (i) a senior clinical staff with certified experience in intensive care medicine available around the clock; (ii) nurse support provided with a nurse/patients ratio ranging from : to : ; (iii) continuous monitoring of electrocardiogram trace, non-invasive blood pressure, oxygen saturation, and respiratory rate. conventional oxygen therapy was referred as applied through venturi or no-rebreathing masks. helmets were the interface systematically used to deliver cpap. niv was equally delivered through mask and helmets. highflow oxygen therapy was adopted in some units as an alternative to cpap. classification into oxygen therapy and non-invasive respiratory support followed the rule of the highest degree of support; accordingly, a patient receiving oxygen therapy at first and then escalating to non-invasive support was classified as receiving non-invasive support. continuous variables were expressed as medians and interquartile ranges (iqr). categorical variables were summarized as counts and percentages. no imputation was made for missing data. statistical analyses were descriptive. comparisons between groups were made using wilcoxon rank-sum and pearson's chi-square. all tests were -tailed and were considered significant if p < . . twenty-eight-day mortality of patients admitted in the icu through the period february -march , and of patients receiving respiratory support outside the icu through the same period was evaluated using the method of kaplan-meier. cumulative incidence of patients extubated and disconnected from mechanical ventilation was calculated and death was considered a competing event. patients were followed up until april th. all the analyses were performed with the use of sas software, version . (sas institute inc., cary, nc). in the period february th-march th, registries of the coordinating centers of lombardy, emilia-romagna and veneto showed that a total of patients were hospitalized for covid- and a total of were admitted and treated in the icu ( . %). data collection forms collected from the participating centers provided information on patients treated in the icu and on patients who received respiratory support outside the icu ( patients in total). notably, the number of patients receiving respiratory support outside the icu increased from ( . %) on february to ( . %) on march (fig. , top) , and the proportion of patients admitted to the icu declined from the . % of hospitalized covid- patients on february to the . % of hospitalized covid- patients on march (fig. , bottom) . compared to patients admitted to the icu, patients receiving respiratory support outside the icu were significantly older, had more cerebrovascular and renal comorbidities and fewer of them were obese. the attending intensivists deemed patients ( . % of the patients treated outside the icu) as non-eligible for further escalation of respiratory support (i.e., for invasive mechanical ventilation). in patients treated outside the icu, conventional o therapy was applied in the . % of the cases and non-invasive respiratory support (including niv, cpap and high-flow o therapy) in the . %, while . % of icu patients were intubated. pao /fio ratio, respiratory rate and arterial ph were higher and paco and base excess were lower in patients receiving respiratory support outside the icu than in patients admitted to the icu. (table ). the infectious disease and the pneumology wards were the most more common locations where out-of-icu respiratory support was delivered ( . % and . %, respectively) ( table ). patients receiving conventional o therapy outside the icu had less cerebrovascular comorbidities and obesity and had significantly higher values of pao /fio and arterial ph than patients receiving noninvasive ventilatory support outside the icu (including niv, cpap and high-flow o therapy). mortality did not differ between patients receiving conventional o therapy and non-invasive respiratory support ( . % vs. . %, respectively; table ). analysis of -day mortality showed a proportion of deaths of . % ( out of ) in patients treated in the icu and of . % ( out of ), in patients receiving respiratory support outside the icu (p = . ). nonsurvivors treated in the icu died within ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days while in non-survivors receiving respiratory support outside the icu death occurred within ( - ) days. fortyfour patients in the icu group ( . %) and patients ( . %) in the out-of-icu group were still hospitalized through april th (last day of follow-up). the present study describes how the italian health-care system of three northern italian regions responded to the increasing need for clinical resources for critically ill patients during the first days of the covid- outbreak through the . % increase in icu beds and the increasing use of non-invasive respiratory support outside the icu. data to evaluate the impact of covid- outbreak on the capacity of the health-care system to accomplish the need for icu resources are limited. xie and coworkers reported that in wuhan as of feb , , there were about patients requiring ventilatory support with new patients every day. however, since only icu beds were available, three general hospitals were rapidly converted to critical care hospitals with a total of about beds dedicated to covid- critically ill patients [ ] . griffin and coworkers described the process to implement an icu surge capacity at the greater new york presbyterian system. in their experience, new covid- icus had to be rapidly assembled after the first weeks from the admission of the first critically ill covid- patients [ ] . concomitantly to the increase in icu bed capacity, there was a progressive increase in the number of patients who received respiratory support outside the icu (from . to . %) under the daily supervision of an intensivist. this allowed to reduce the percentage of patients admitted to the icu from . % on february th to . % on march th. the response between the italian and the greater new york presbyterian systems was similar, despite the different icu capacity ( . % of the total hospital beds in the usa [ ] vs. . % in italy (https ://www.salut e.gov.it/imgs/c_ _pubbl icazi oni_ _alleg ato.pdf ). this might be explained by the extensive use of out-of-icu respiratory support we adopted in italy [ ] [ ] [ ] . our data show that, compared to patients admitted to the icu, patients receiving respiratory support outside the icu were significantly older, had more comorbidities and had a higher pao /fio ratio and a lower paco . among patients treated outside the icu, proportions of patients treated with conventional o therapy and noninvasive respiratory support were comparable ( . vs. . %, respectively). the median age of our icu population [ years ( - )] is consistent with the one reported at national level in pre-pandemic times [ ] and, although it is difficult to draw conclusion from these data, it is probable that the same age criteria were adopted during the first weeks of the covid- epidemics in northern italy. patients receiving conventional o therapy outside the icu showed a pao /fio ratio higher than those receiving non-invasive support outside the icu, without differences in age and mortality. although a crude comparison of mortality is not very informative because of the baseline differences between the icu and outof-icu populations, we show here that the difference in survival at days in patients treated in the icu and those receiving respiratory support outside the icu was small ( . vs. . %, respectively). altogether these data seem to suggest that treatment outside the icu has been offered as a therapeutic setting proportional to patient's conditions and not as a 'limited' standard of care, always remaining within the ethical perimeter of standard clinical practice [ , ] . nevertheless, is unlikely that all eligible patients were transferred to an icu, and we cannot exclude that at least some patients who matched criteria for icu admission did not survive long enough to be transferred to icu or comorbid disease or goals of care precluded escalation to icu level care. non-invasive ventilation was suggested to be avoided in covid- patients due to the risk of transmission of infection [ ] . in our hospitals, the risk might have been reduced for the following reasons: (a) helmets equipped with high-efficiency particulate air filters at the peep port were the interface of choice for delivering non-invasive respiratory support in almost / of patients treated outside the icu; this interface might have avoided the dispersion of the multiphase turbulent gas cloud from coughing and sneezing on part of the patients, possibly reducing the transmission of covid- [ ] ; (b) about % of the patients receiving respiratory support outside the icu were treated in infectious disease wards that are commonly equipped with negative pressure rooms [ ] . moreover, there is growing evidence that niv can be safely performed outside the icu in covid- patients, and even advanced maneuvers such as prone positioning have been successfully tested in these patients [ ] . these data have may important implications for the reorganization required by health-care systems necessary to manage the covid- outbreak. the italian society of anesthesia, analgesia, resuscitation, and intensive care (siaarti) recommended an approach for resource allocation based on "clinical appropriateness" and "distributive justice" in case of significant mismatch between the number of patients requiring icu admission and the available resources and acknowledged that: "it is not about making choices on value, but to reserve possibly scarce resources first to who has higher probability of survival and second to who can have higher saved years of life, with the purpose of maximizing benefits for the highest possible number of people" [ ] . our data show that increasing the icu capacity by . % obtained through the reorganization of available facilities (conversion of operating rooms, coronary units, closure of all scheduled surgical activity) and use of out-of-icu respiratory support [ ] [ ] [ ] , the healthcare system was able to accomplish the clinical needs for respiratory support in covid- patients and may suggest that end-of-life practices might have remained within the ethical perimeter of standard clinical practice [ , ] . the retrospective nature represents the major weakness of this study. although data have been collected by personnel with experience in clinical research and strongly motivated to share their experience, the enormous clinical load and the risk of contagion have certainly influenced the quality of the data and limited the number of information that has been possible to collect. moreover, further analysis is needed to provide information regarding use of resources, allocation of beds, staffing choices, timing of opening up of new beds, and what resources were most stretched in the first weeks. moreover, the expected heterogeneity in hospital capacity and care practices between study hospitals may limit the practical utility of the description for clinicians facing an imminent surge of patients with covid- disease. despite these limitations, this study represents the first and most detailed description of the clinical reality of the first western country overwhelmed by the covid- epidemic. in conclusion, although our analysis confirms the grave concerns regarding the capacity of health-care systems to effectively respond to the covid- outbreak, these data show that the rapid increase in beds obtained through the reversal of already available resources into intensive care facilities and the use of out-of-icu respiratory support allowed to manage the first terrible days of the covid- outbreak. the present analysis shows that only rapid acquisition of new intensive care facilities with appropriate equipment and personnel and use of out-of-icu respiratory support [ ] [ ] [ ] may avoid the rationing of health-care resources that may be acceptable for "battlefield medicine", but should be incompatible with health-care systems founded on the principles of universality, solidarity and distributive justice (article of the constitution of the italian republic and law number december rd, ). manerbio (italy), benvenuto.antonini@asst-garda.it; nicolangela belgiorno, istituto clinico san rocco ), massimo_borelli@asst-bgovest.it; luca cabrini, ospedale di circolo e fondazione macchi, varese (italy), luca.cabrini@uninsubria.it; livio carnevale busto arsizio (italy), daniel.covello@asst-valleolona.it; gianluca de filippi, asst rhodense-presidio ospedaliero g milan (italy), deipolimd@gmail.com; paolo dughi, asst franciacorta -presidio ospedaliero di iseo vimercate (italy), giorgio.gallioli@asst-vimercate.it; paolo gnesin saronno (italy), stefano.greco@asst-valleolona.it; luca guatteri, ospedale "sacra famiglia" fatebenefratelli seriate (italy), roberto.keim@asst-bergamoest.it; giovanni landoni melegnano (italy), giovanni.marino@asst-melegnanomartesana.it; guido merli, asst crema-ospedale maggiore di crema, crema (italy), guido.merli@asst-crema.it; dario merlo fondazione poliambulanza istituto ospedaliero, brescia (italy), giuseppe.natalini@gmail. com; nicola petrucci, asst garda-ospedale di desenzano d/g, desenzano del garda (italy), nicola.petrucci@asst-garda legnano (italy), danilo.radrizzani@asst-ovestmi.it; maurizio raimondi, asst pavia-ospedale civile di voghera ), enrico.storti@asst-lodi.it; mario tavola zingonia (italy), giovanni.vitale@ grupposandonato.it mirano (italy), mauroantonio.calo@aulss .veneto.it; vinicio danzi, u.o.c anestesia e rianimazione ospedale cà foncello, treviso (italy), antonio.farnia@aulss .veneto.it; francesco lazzari, u.o.c. anestesia e rianimazione, ospedale dell azienda zero del veneto, padova (italy), mario.saia@azero.veneto.it; nicolò sella, u.o.c. istituto di anestesia e rianimazione, azienda ospedale università padova, nico.sella@hotmail.it; eugenio serra, u.o.c. istituto di anestesia e rianimazione, azienda ospedale università di padova, padova, eugenio.serra@ aopd.veneto.it; ivo tiberio, u.o.c. anestesia e rianimazione, azienda ospedale università padova, ivo.tiberio@aulss .veneto.it (italy), martina.bordini @studio.unibo.it; fabio caramelli, policlinico sant'orsola malpighi (italy), guido.frascaroli@aosp.bo.it; maurizio fusari, ospedale "santa maria delle croci (italy), costanza.martino@auslromagna.it; raffaele merola, policlinico sant'orsola-malpighi (italy), mrofrc@ unife.it; giuseppe nardi, ospedale "infermi rimini (italy), antonella.potalivo@auslromagna.it; francesca repetti, ausl piacenza, piacenza (italy), francesca.repetti@hotmail.it; pierpaolo salsi, azienda ospedaliera santa maria nuova, reggio emilia (italy), salsi.pierpaolo@ausl.re.it; marina terzitta modena (italy), tosimartina@gmail.com; sergio venturi, emergency commissioner for emilia-romagna region, sergio arcispedale sant' anna clinical characteristics of coronavirus disease , in china clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a singlecentered, retrospective, observational study clinical characteristics of hospitalized patients with, novel coronavirus-infected pneumonia in wuhan china baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region italy characteristics and outcomes of critically ill patients with covid- in washington state critical care crisis and some recommendations during the covid- epidemic in china critical care utilization for the covid- outbreak in lombardy, italy: early experience and forecast during an emergency response covid- and italy: what next? lancet facing covid- in italy-ethics, logistics, and therapeutics on the epidemic's front line clinical features of patients infected with novel coronavirus in wuhan china early cpap prevents evolution of acute lung injury in patients with hematologic malignancy introducing critical care outreach: a ward-randomised trial of phased introduction in a general hospital effect of the critical care outreach team on patient survival to discharge from hospital and readmission to critical care: non-randomised population based study aerosol and surface stability of sars-cov- as compared with sars-cov- hospital preparedness for covid- : a practical guide from a critical care perspective critical care bed growth in the united states: a comparison of regional and national trends the influence of gender on the epidemiology of and outcome from severe sepsis changes in end-of-life practices in european intensive care units from to withholding or withdrawing of life-sustaining therapy in older adults (>/= years) admitted to the intensive care unit turbulent gas clouds and respiratory pathogen emissions: potential implications for reducing transmission of covid- protecting healthcare workers from sars-cov- infection: practical indications respiratory parameters in patients with covid- after using noninvasive ventilation in the prone position outside the intensive care unit it/sitea ssets /news/covid % -% d ocume nti% s iaart i/siaar ti% -% c ovid- % -% c linic al% e thics % r eccom endat ions members of the covid- northern italian icu network: lombardy: giovanni albano, humanitas gavazzeni, bergamo (italy), giovanni.albano@gavazzeni.it; armando alborghetti, policlinico san pietro-ponte san pietro (italy), armando.alborghetti@grupposandonato.it; giorgio aldegheri, irccs tt, gg, az, pn, mc, fl, pv, ma, sn were responsible for study design, data acquisition, analysis, interpretation, and preparing the first draft of the manuscript. gp, rf, sp, ll, gi, gf, sc, lv, sr, mg, va, ac, gg, ab, ag, av, iv, dc, cf, mb mg, were responsible for data acquisition and data interpretation. ap and vmr were responsible for study design, data acquisition, analysis, interpretation, finalize the manuscript and study data integrity. all authors had an opportunity to review the manuscript and approved its final submitted version. no funding was provided. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. the study was approved by the coordinating center's irb (comitato etico avec, bologna, italy) with approval number / /oss/aoubo; participant centers obtained approval from their respective irbs; consent to participate was waived for unresponsive, uncommunicative or deceased patients, in accordance to rule / of the italian privacy authority. key: cord- -u dfp gf authors: toubiana, julie; courtine, emilie; tores, frederic; asfar, pierre; daubin, cédric; rousseau, christophe; ouaaz, fatah; marin, nathalie; cariou, alain; chiche, jean-daniel; mira, jean-paul title: association of rel polymorphisms and outcome of patients with septic shock date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: u dfp gf background: crel, a subunit of nf-κb, is implicated in the inflammatory response observed in autoimmune disease. hence, knocked-out mice for crel had a significantly higher mortality, providing new and important functions of crel in the physiopathology of septic shock. whether genetic variants in the human rel gene are associated with severity of septic shock is unknown. methods: we genotyped a population of icu patients with septic shock and icu controls for two known polymorphisms of rel; rel rs and rel rs . outcome of patients according to the presence of rel variant alleles was compared. results: the distribution of rel variant alleles was not significantly different between patients and controls. among the septic shock group, rel rs *t minor allele was not associated with worse outcome. in contrast, rel rs *g minor allele was significantly associated with more multi-organ failure and early death [or . ; % ci ( . – . )]. conclusion: in a large icu population, we report a significant clinical association between a variation in the human rel gene and severity and mortality of septic shock, suggesting for the first time a new insight into the role of crel in response to infection in humans. despite continued efforts and significant advances in critical care medicine, septic shock remains a significant health problem with a mortality rate around % [ , ] . septic shock is defined as sepsis accompanied by cardiovascular failure that is often a part of multiple organ dysfunction syndrome (mods) [ ] . thus, septic shock represents an extreme manifestation of the host inflammatory response to severe infection. transcription of inflammatory mediators such as cytokines, chemokines, adhesion molecules and reactive oxygen species is strongly activated by the transcriptional factor nf-κb and contributes to the development of mods [ , ] . nf-κb is an ubiquitous family of inducible dimeric homodimer or heterodimer transcriptional factors composed by five members: rel (c-rel), rela (p ), relb, nf-κb (p /p ) and nf-κb (p /p ) [ ] . the role of rela in severe infection is well established, as it is highly recruited to the promoter of pro-inflammatory genes in non-survivors of septic shock [ , ] . the crel subunit was the least studied member of the rel family, but seems to have also a critical role in the antimicrobial host defense. indeed, in vivo studies revealed that crel is required for macrophage activation [ , ] , adaptive immunity [ ] and the control of lymphocyte proliferation [ , ] . crel is also a key regulator of numerous cytokines: il- , il- , il- , il- , il- , il- , il- , il- , ifn-γ, ifn-β, ifn-λ, mip -α and gm-csf [ , [ ] [ ] [ ] [ ] [ ] [ ] . more recently, in a murine model of polymicrobial sepsis, rel deficiency led to an increased mortality, an enhanced systemic inflammatory response and a sustained depletion of spleen lymphoid dendritic cells [ ] [ ] [ ] [ ] ] . furthermore, whole blood transcriptomics showed that crel targets inflammatory and survival genes during sepsis [ , ] . moreover, genetic variants within the rel locus have been associated with inflammatory diseases or autoimmunity in europeans [ ] . even if no study reports the importance of crel in human sepsis, these elements highlight the potential importance of crel for nf-κb targeted-immunomodulation in severe infections. recently, the role of genetic factors influencing the susceptibility to or the severity of severe sepsis has been extensively studied. several single nucleotide polymorphisms (snps) have been characterized in genes of nf-κb pathway proteins. for instance, snps in tlrs [ ] [ ] [ ] , tirap [ ] , irak [ , ] , iκb [ ] and nf-κb inducing kinase (nik) [ ] genes have been associated with severity of sepsis. however, the association between genetic variants in nf-κb subunits and severe infections has been poorly reported. hence, the present study aims to test the hypothesis of an association between clinically significant rel genetic variants and severity of septic shock in a large cohort of well-defined intensive care unit (icu) patients. this study was conducted prospectively in three medical icus in france. all three icus share similar severe sepsis management protocols based on international guidelines from the surviving sepsis campaign for management of severe sepsis/septic shock [ ] . the septic shock group was defined by usual criteria [ ] . briefly, patients were eligible for inclusion into the septic shock group (ss) if they had, within their stay in icu, a clinical evidence of infection with two of four sirs criteria (fever (> . °c) or hypothermia (< °c); tachycardia (> beats/min); tachypnea (> breaths/min) or need of mechanical ventilation; white cell count > × /l) and if, after an adequate fluid resuscitation, they required vasopressor infusion (norepinephrine, epinephrine or dopamine > μg/kg/min) to maintain a mean arterial pressure higher than mmhg. exclusion criteria included comorbidities highly associated with death in ss [ ] : age above years, cardiac failure (nyha class iii or iv), liver insufficiency (child c), bone marrow aplasia or leucopenia not related to septic shock (white blood cell count < . × /l), immunosuppression (hiv, current immunosuppressive therapy including steroids with equivalent prednisone > . mg/kg per day) or ongoing cancer with undergoing treatment. the control group (c) was composed of patients hospitalized simultaneously in the three icus for other reasons than infection and who did not develop sepsis nor required any inotropic or vasopressor agents during their icu stay. similar exclusion criteria were used for the control and the ss groups. patients were followed up throughout their icu stay, and clinical and biological characteristics were prospectively collected: age, gender, sapsii score and previous medical history of severe infection requiring hospitalization. for the ss group, characteristics of current infectious episode were also collected: primary sites of infection, infection-related microorganisms, development of multi-organ dysfunction syndrome (mods) (defined as the presence of more than two organ system failures occurring simultaneously icu stay) [ ] , mechanical ventilation requirement estimated by ventilator-free day (vfd: time without mechanical ventilation within the icu period censured to days) [ ] and icu mortality. to minimize confounding factors due to ethnical differences, all patients selected in the study were caucasians and had european origins. the institutional review board of cochin hospital, paris, france, approved the study, and informed consents have been obtained from the patients or their relatives. two previously described snp have been analyzed. the snp rs is a a → g transition located in the second intron of rel gene on chromosome (chromosomic location ). the snp rs is a g → t transition located in the fourth intron of rel gene (chromosomic location ). all genetic analyses were performed blinded from the clinical data. genomic dna was extracted from mononuclear cells using magna pure compact automate (roche diagnostics ® ). dna extracts were then quantified and stored in code-barr tubes ( dcypher, abgene ® ) to maintain anonymous status of the patients all along the study. real-time pcr allelic discrimination assays were realized by taqman ® method on abi (applied biosystems ® ). probe and primer combinations were designed to discriminate the two rel snps (rs and rs ). quality control for genotyping was performed by automatic sequencing patients carrying the different rel genotypes in order to confirm allelic discrimination results and also by re-genotyping % of the entire cohort. all dna samples showing discrepancy between the two analyses were definitively sequenced (n = ). all data were analyzed by spss v . and "r" v softwares. both snps were tested for hardy-weinberg disequilibrium to check for stratification. in order to calculate the Šidák multiple testing correction, we first evaluate the effective number of independent tests (called meff ) in the analysis by using the methodology proposed by li and ji [ ] . this method aims to prevent from overcorrection due to possible linkage disequilibrium (ld) between the snps. power calculation has been based on the frequency of the variant allele in the control population as proposed by hattersley et al. [ ] . hence, for an incidence of the variant allele of % in the control population and a power at %, a % increase in the case population with a type i error of %, individuals in each group appear to be sufficient to detect genetic susceptibility to ss (http://www.stat.ubc.ca/~rollin/stats/ssize/b .html). for the second study assessing the prognostic value of the variant alleles in ss group, given the frequency of the variant genotype, and an expecting mortality rate at - % in the ss subgroup group, we considered that ss patients were sufficient for a power at . (type i error at . ) to identify a % difference in genotype frequency. descriptive results of continuous variables were expressed as median and interquartile range reflecting population distribution. variables were tested with chisquare test for categorical data (sex, multi-organ failure, primary sites of infection, microorganisms, genotypes) and with mann-whitney u test for numerical data (age, sapsii, vfd). a multivariate logistic regression model was used to determine the respective role of rel genotypes for susceptibility to ss and to icu mortality. confounding factors with a p value < . were included in this model. continuous variables were included without any transformation, and genotypes were considered as a factor (dichotomous unordered variate) to avoid the implicit dose effect when coding the genotypes , and according to the number of mutated alleles carried. results were expressed as odds ratio (or) and % confidence interval (ci), and variable with p value < . was defined as statistically significant. the total enrolled caucasian population was composed by septic shock patients (ss) and controls (c). in the c group, enrolled icu patients were admitted for various non-infectious reasons (metabolic: %, neurological: %, respiratory: %, cardiovascular: % and surgical: %) and did not develop severe sepsis and did not require vasopressor infusion during their icu stay. c patients were younger than ss patients ( vs . years, respectively, p = . ), and females were more represented in c group ( and %, for c and ss, respectively, p = . ). mortality rate and occurrence of mods in the c group were and %, respectively. all ss patients received norepinephrine or epinephrine as first vasopressor. the main site of infection was the lung ( %); microorganisms were identified in % of the cases, mainly gram-positive bacteria. median sapsii value of and high percentage of patients with multiple organ dysfunctions ( %) underlined the severity of the septic shock population. the icu mortality rate of the ss group was %. hardy-weinberg proportions were comparable to expected percentages regarding rel variants: rel rs (p = . ) and rel rs (p = . ) in favor of homogeneity of population ethnicity. to determine whether rel rs and rs snps were associated with septic shock susceptibility, genotype frequencies were determined for ss and c patients. as reported in table , no significant difference was found between the two groups. moreover, these incidences were similar to those reported in the hapmap database-reported genotype distribution for european population (http:// www.ncbi.nhm.nih.gov/projects/snp/snp_viewtable. cgi?pop= ). among the ss patients, general clinical characteristics were not significantly different between patients carrying rel minor allele and patients homozygous for major allele on both rel-analyzed loci ( table ). in order to study the link between rel snps and septic shock severity, we compared acute respiratory distress syndrome (ards) and mods frequencies, and vfd value between patients carrying rel rs *g and rs *t minor alleles and in those homozygous for the major alleles. as given in table , vfd values were table ]. for multiple testing correction, we calculated a meff of . [ ] leading to a corrected p value of . . a similar trend was observed for ards (p = . , table ). in ss group, mortality was not significantly different between patients carrying rel rs *t minor allele and homozygous for the major allele of this snp ( . vs. . %, for minor and major alleles, respectively, p = . ). in contrast, the presence of the rs *g minor allele was significantly associated with a higher mortality rate ( vs. %, for minor and major alleles, respectively, p = . ) (fig. ) the present study showed that septic shock patients carrying the rs *g minor allele had an over risk of mods and mortality. in contrast, no association was found between the rel rs *t allele and the severity of septic shock. this study was the first to investigate the importance of two polymorphisms within rel gene in a large european population of septic shock patients. several human studies have suggested that these variants may have an effect on the inflammatory balance, as they have been associated with inflammatory and autoimmune diseases. indeed, the intronic rs snp in the rel gene was associated with susceptibility to rheumatoid arthritis [ ] [ ] [ ] and psoriasis [ ] . the intronic rs snp was linked to a higher risk of crohn's disease, ulcerative colitis [ ] and celiac disease [ , ] and primary sclerosing cholangitis [ ] . genome-wide studies have also found that rel locus was associated with psoriasis [ , ] , rheumatoid arthritis [ ] , ulcerative colitis [ , ] and hodgkin's lymphoma [ ] . however, functional and structural effects of these polymorphisms are still unknown and need to be investigated. given that variant alleles are located on an intronic site, it is possible that these polymorphisms affect transcriptional efficiency of rel gene or these variants may be in strong linkage disequilibrium with a variant inside a neighbor gene. the higher rate of mortality observed in ss patients carrying rs *g might be linked to a higher inflammatory state, as they also developed more frequently mods. they also tend to have more ards and lower vfds however not significant, but this is most likely underpowered, as vfds are not normally distributed. mortality in septic shock was partially related to hyperactivation of nf-κb [ , ] . in this setting, previous genetic studies on several gain of function snps in genes of receptors and signaling molecules upstream of nf-κb, such as tlr and irak [ , ] , showed a significant association with severity of sepsis. these genetic factors might unbalance the fine-tune regulation toward a hyperinflammatory deleterious state. however, the exact role of crel on inflammatory processes is less understood in humans. recent studies have shown that crel could be involved in autoimmunity, such as inflammatory arthritis [ ] and autoimmune encephalomyelitis [ ] . more recently, crel was shown to have a key role in antimicrobial defense processes. rel−/− mice are more susceptible to leishmania major [ ] or toxoplasma gondii infections [ ] , to viral infection by influenza virus [ ] , to bacterial infection by listeria monocytogenes [ ] and to polymicrobial sepsis [ ] . crel is probably important in pro-/ anti-inflammatory balance as rel−/− mice seemed to have an enhanced inflammatory response [ ] . the study design quality is important for a right interpretation of genetic association studies [ ] . we tried to follow closely these quality criteria. first, it is important to select a snp of a protein involved in the physiopathology of the disease. as already mentioned, rel seems to be an interesting gene to study because nf-κb plays a central role in physiopathology of sepsis, and recent studies show the importance of crel in this context. however, one important limit of our study is the absence of data regarding the functional effect of these two snps. functional data are needed to improve our understanding of how rs *g variant of rel is related to sepsis severity. second, the population homogeneity has been controlled by limiting the study on european patients without severe comorbidities. the third item is probably one of the more controversial in the sepsis field: choice of a clearly defined phenotype to avoid confusion factors. thus, we have selected only patients with septic shock whose diagnosis and treatment are standardized [ ] , and these patients had no major comorbidity or immunosuppressive treatment, severe autoimmune diseases in particular, that could have been confounding the results. however, it is impossible to rule out effects of confounding factors or gene-environment interactions in our results, and septic shock is heterogeneous with regard to the source of infection. sample size is essential for statistics quality in association study but is difficult to achieve in pure septic shock population. at our knowledge, our cohort is one of the largest ever published populations in this topic and is large enough to diminish type i error. it is important to consider that after correction for multiple testing, our result only reached near significance. Šidák/ bonferroni correction assumes, however, that markers are independent, whereas the snps studied here are in ld and are therefore not truly independent from each other. as a result, though we tried to take into account ld by the calculation of meff, the adjustment is likely to overcorrect in this case. we therefore consider that our preliminary results would need a validation in independent cohorts. finally, this genetic association study is limited to one gene. genome-wide association studies (gwas) are now discovering new unsuspected genes that might have an impact on sepsis outcome [ ] . the association between rs *g allele and severity of septic shock brings a new perspective on the role of crel subunit of nf-κb in severe infections in humans. better understanding of the genetic effects of nf-κbdependent inflammatory pathways is essential for further research on modulation of nf-κb activity by specific inhibitors, such as small molecule inhibitors of crel, as an adjuvant treatment for sepsis [ , ] . further studies are needed to investigate the functional role of this rel polymorphism on the inflammatory processes observed in sepsis and to validate these encouraging results in independent cohort. abbreviations mods: multiple organ dysfunction syndrome; il: interleukin; ifn: interferon; snp: single nucleotide polymorphisms; icu: intensive care unit; ss: septic shock group; c: control group; vfd: ventilator-free day; ards: acute respiratory distress syndrome; ld: linkage disequilibrium; tlr: toll-like receptor. severe sepsis and septic shock epidemiology of severe sepsis surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock nf-kappa b activation as a pathological mechanism of septic shock and inflammation the two nf-kappab activation pathways and their role in innate and adaptive immunity characterization of elements determining the dimerization properties of relb and p predictive value of nuclear factor kappab activity and plasma cytokine levels in patients with sepsis role of nfkappab in the mortality of sepsis the rel subunit of nf-kappab-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for rel in different macrophage populations cutting edge: identification of c-rel-dependent and -independent pathways of il- production during infectious and inflammatory stimuli mice lacking the transcription factor subunit rel can clear an influenza infection and have functional anti-viral cytotoxic t cells but do not develop an optimal antibody response multiple hemopoietic defects and lymphoid hyperplasia in mice lacking the transcriptional activation domain of the c-rel protein genomewide analysis of gene expression in t cells to identify targets of the nf-kappa b transcription factor c-rel the roles of c-rel and interleukin- in tolerance: a molecular explanation of self-nonself discrimination il- rescues the hyporesponsiveness of c-rel deficient b cells independent of bcl-xl, mcl- , and bcl- interferon regulatory factor- activates il- and il- promoters in cooperation with c-rel regulation of the il- gene by the nf-kappab transcription factor c-rel regulation of ifn-lambda promoter activity (ifn-lambda /il- ) in human airway epithelial cells nuclear factor kappab subunits relb and crel negatively regulate toll-like receptor -mediated beta-interferon production via induction of transcriptional repressor protein yy critical role of crel subunit of nf-kappab in sepsis survival the c-rel transcription factor in development and disease toll-like receptor polymorphisms affect innate immune responses and outcomes in sepsis a common dominant tlr stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease relevance of mutations in the tlr receptor in patients with gram-negative septic shock a mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis irak functional genetic variant affects severity of septic shock variant irak- haplotype is associated with increased nuclear factor-kappab activation and worse outcomes in sepsis ikappab genetic polymorphisms and invasive pneumococcal disease a single nucleotide polymorphism in nf-kappab inducing kinase is associated with mortality in septic shock surviving sepsis campaign guidelines for management of severe sepsis and septic shock definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter prospective study in intensive care units. french icu group for severe sepsis statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix what makes a good genetic association study? confirmation of association of the rel locus with rheumatoid arthritis susceptibility in the uk population encoding a member of the nf-kappab family of transcription factors, is a newly defined risk locus for rheumatoid arthritis genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci an investigation of rheumatoid arthritis loci in patients with early-onset psoriasis validates association of the rel gene genetic analysis of innate immunity in crohn's disease and ulcerative colitis identifies two susceptibility loci harboring card and il rap coeliac disease-associated risk variants in tnfaip and rel implicate altered nf-kappab signalling improving the estimation of celiac disease sibling risk by non-hla genes three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for il , rel, and card a genome-wide association study identifies new psoriasis susceptibility loci and an interaction between hla-c and erap genome-wide association identifies multiple ulcerative colitis susceptibility loci ulcerative colitis-risk loci on chromosomes p and q found by genome-wide association study a genome-wide association study of hodgkin's lymphoma identifies new susceptibility loci at p . (rel), q . and p (gata ) nuclear factor-kappab activation in peripheral blood mononuclear cells in children with sepsis distinct roles for the nf-kappab (p ) and c-rel transcription factors in inflammatory arthritis critical roles of c-rel in autoimmune inflammation and helper t cell differentiation genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study the ikk nf-kappa b system: a treasure trove for drug development a small-molecule c-rel inhibitor reduces alloactivation of t cells without compromising antitumor activity this study was supported by national grant from the ministry of health (phrc ), grant from carisma (cochin association for research in inflammation, sepsis and molecular advances), grant from srlf (société de réanimation de langue française) and grant from sfar (société française anesthésie réanimation. these funding organizations played no role in the design, execution and publication of the study. jt and jpm participated in the design of the study and the interpretation of the data. jdc, ac, pa, nm and cd participated in the recruitment of patients; ec and jt in the redaction and revision of the manuscript; and ft checked the statistics. cr and fo performed the genotyping experiments. all the authors reviewed the manuscript. all authors read and approved the final manuscript. the authors declare that they have no competing interests. key: cord- -nki sasr authors: vidaur, loreto; totorika, izarne; montes, milagrosa; vicente, diego; rello, jordi; cilla, gustavo title: human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis date: - - journal: ann intensive care doi: . /s - - -y sha: doc_id: cord_uid: nki sasr background: information on the clinical, epidemiological and molecular characterization of human metapneumovirus in critically ill adult patients with severe community-acquired pneumonia (cap) and the role of biomarkers identifying bacterial coinfection is scarce. methods: this is a retrospective epidemiological study of adult patients with hmpv severe cap admitted to icu during a ten-year period with admission psi score ≥ . results: the . % of the patients with severe cap due to human metapneumovirus were detected during the first half of the year. median age was years and . % were male. the genotyping of isolated human metapneumovirus showed group b predominance ( . %). all patients had acute respiratory failure. median apache ii and sofa score were and . , respectively. the % were coinfected with streptococcus pneumoniae. . % of the patients had shock at admission and % underwent mechanical ventilation. seven patients developed ards, three of them younger than years and without comorbidities. mortality in icu was . %. among survivors, icu and hospital stay were . and days, respectively. plasma levels of procalcitonin were higher in patients with bacterial coinfection ( . vs . ; p < . ). the levels of c-reactive protein, however, were similar. conclusion: human metapneumovirus was associated with severe cap requiring icu admission among elderly patients or patients with comorbidities, but also in healthy young subjects. these patients often underwent mechanical ventilation with elevated health resource consumption. while one out of four patients showed pneumococcal coinfection, plasma procalcitonin helped to implement antimicrobial stewardship. electronic supplementary material: the online version of this article ( . /s - - -y) contains supplementary material, which is available to authorized users. human metapneumovirus (hmpv) is a worldwide distributed enveloped virus with a rna genome closely related to respiratory syncytial virus. hmpv belongs to the paramyxoviridae family, in the genus metapneumovirus, first identified in the netherlands in [ ] . based on genetic and antigenic variability, hmpv strains have been classified in two groups or lineages (a and b) and four sublineages (a , a , b and b ) [ ] [ ] [ ] . the virus has been reported as a common respiratory pathogen in childhood, associated mainly with upper but also with lower respiratory tract infections [ , ] . during the annual epidemics, hmpv has been associated with a significant number of hospital admissions in young children [ ] [ ] [ ] [ ] . respiratory tract infections caused by hmpv during adulthood are less prevalent and less serious than those open access *correspondence: loretovidaurtello@gmail.com critical care department, donostia university hospital-biodonostia health research institute, san sebastian, guipuzcoa, spain full list of author information is available at the end of the article in childhood. however, the presence of hmpv has been detected in - % of adult patients admitted due to a community-acquired pneumonia (cap) [ , ] and has been associated with asthma and chronic obstructive pulmonary disease exacerbation [ ] [ ] [ ] . the same as with other common respiratory viruses, hmpv is usually associated with non-severe pneumonia, whereas risk factors like immunosuppression, specific comorbidities-chronic lung disease, heart disease, blood disorders-elderly and living in long-term care facilities are associated with a higher risk of severe viral pneumonia [ , ] . nevertheless, recent studies suggest that hmpv infection is an underappreciated cause of critical illness, also in previously healthy patients [ ] [ ] [ ] [ ] . severe community-acquired pneumonia (scap) is a known infectious complication of respiratory viruses including hmpv. in these cases, clinical presentation, evolution and treatment differ depending on the pathogens involved, hmpv alone or hmpv coinfected with a bacteria. some biomarkers have been studied as diagnostic markers to discriminate between viral or bacterial pneumonias and help physicians to decide not to start or when to withdraw the antibiotic therapy [ , ] . the main objective of this study was to describe the clinical and epidemiological characteristics of adults with severe pneumonia caused by hmpv who required intensive care unit (icu) admission, over a long period of time. secondary objectives were to characterize the epidemiological and molecular viral diversity and to compare the value of c-reactive protein (crp) and procalcitonin in identifying bacterial coinfections. this is a ten-year, retrospective epidemiological study with inclusion of patients with cap due to hmpv admitted in a -bed icu in the north of spain. in , this icu assisted a referral population of , inhabitants older than years. all patients older than years from july to june admitted in the icu by cap with admission psi score ≥ were considered eligible. during the first years of the study, samples to detect respiratory viruses were obtained occasionally in patients with cap. however, it turned the standard of care in the icu after influenza pandemic. to be included, cases meet two of the following three criteria upon admission: (a) severe acute respiratory failure (pao /fio < ), (b) multilobar radiological involvement or (c) systolic arterial pressure < mmhg. acute respiratory distress syndrome (ards) was diagnosed as an acute diffuse lung injury with increased vascular permeability, bilateral radiographic opacities and hypoxemia not fully explained by cardiac failure or fluid overload following the berlin criteria [ ] . exclusion criteria: subjects with nosocomial pneumonia or admitted due to non-respiratory infection (non-severe coincidental infection) and patients with pneumonia during the preceding months (persistence of viral rna in respiratory samples). patients were recruited from the computerized records of the microbiology department, and the medical records were revised by two clinical investigators (it, lv). the recorded clinical variables were socio-demographic (age and sex), comorbidities, the charlson comorbidity score and clinical symptoms at admission [ ] . radiological and analytic findings at admission and during the evolution, coinfections, antibiotic therapy, the presence of shock or need of mechanical ventilation, icu and hospital stay were also recorded. the detection of hmpv in respiratory samples was made by reverse transcription polymerase chain reaction (rt-pcr), in house monoplex until july [ ] , real-time commercial multiplex (luminex xtag respiratory viral panel [usa]) until july and seegene anyplex ™ ii rv /allplex ™ respiratory panel [republic of korea] since then. the extraction of nucleic acids was made using an automatic biorobot m extractor (qiagen gmbh, hilden, germany) until july and the nuclisens ® easy-mag platform (bio-mèrieux sa, marcy l'etoile, france) from that date. the genotyping of hmpv was performed with a rt-pcr followed by sequencing [ ] . blood cultures, streptococcus pneumoniae and legionella pneumophila antigenuria (alere binaxnow, scarborough, me, usa), and pharyngeal exudates with viral transport media to evaluate respiratory viruses were assessed in all the patients included in the study. coinfection was considered when hmpv was isolated with other viral or bacterial pathogens at the same time. discrete variables were expressed as counts (percentage) and continuous variables as medians and - % interquartile ranges (iqrs). differences in continuous variables were analyzed by the mann-whitney u test or the kruskall-wallis test when appropriate. qualitative variables were analyzed by the chi-square test with yate's correction when necessary. the threshold for clinical significance was p < . . data analysis was performed using spss for windows . . (spss, chicago, il, usa). the obtained clinical samples and the medical intervention of the patients were ordered by the clinician attending each patient. the study was approved by the ethics committee for clinical research of the health area of gipuzkoa (spain). informed consent was waived due to the retrospective nature of the study. during the study period, respiratory samples were sent from the icu to the microbiology service to study viral etiology, hmpv being identified in patients ( . %). studied samples were mainly pharyngeal exudates ( . %), but also tracheal aspirates ( . %), bronchoaspirates ( . %), bronchoalveolar lavages ( . %) and sputum ( . %), where bacterial culture was also performed. five patients with hmpv were excluded because admission causes were other than respiratory infection. cases were detected every year except in (n = - ). the highest prevalence was in and (fig. ) . twenty-six of the patients with respiratory infection due to hmpv ( . %) were detected during the first half of the year and ( . %) in march-april. hmpv circulated every year later than influenza virus, being the epidemic peak of both infections separated by a period of - months. in fact, the % of cases ( / ) of hmpv infections in patients admitted to icu occurred out of the influenza epidemic period ( table ) . genotyping of hmpv was performed in cases, being ten cases of hmpv group a ( . %) and of hmpv group b ( . %). the viral strains belonged to sublineages a (n = ; . %), b (n = ; . %) and b (n = ; . %). group a strains predominated until ( . %), while later, the most frequent was genotype b ( %). after excluding seven patients with bacterial coinfection, there were not significant differences in the genotype of hmpv between six patients who developed ards ( % genotype b) and who did not ( % genotype b). at icu admission, all patients had acute respiratory failure and received empiric antibiotic therapy. median apache ii score was , and median saps iii and sofa scores were . [iqr . - . ] and . [iqr . - . ], respectively. median age of the included patients was years [ - % iqr . - . ], and . % of them were under years old ( with less than two comorbidities). the . % (n = ) of the patients were male. main symptoms at admission were cough ( . %), dyspnea ( . %), fever ( . %) and purulent respiratory secretions ( . %). nineteen patients ( . %) had major comorbidities such as immune compromise (n = ), asthma (n = ) or chronic respiratory disease (n = ) ( table ) . seven patients (none died) had coinfection with streptococcus pneumoniae. three episodes were coinfected with viral pathogens: human parainfluenza virus type (hpiv ), human rhinovirus and cytomegalovirus (last one in an immunosuppressed patient). predominant radiologic pattern in patients with hmpv infection and without coinfection was the interstitial alveolar pattern ( . %), while in the patients with streptococcus pneumoniae coinfection, the alveolar pattern was predominant ( . %). eight patients had pleural effusion at admission, and two more developed it during the icu stay. pleural effusion was bilateral in four patients and massive (> l) in three cases. seventeen ( . %) patients had shock at admission, fourteen ( %) underwent invasive mechanical ventilation (median . days [iqr - . ]) due to acute respiratory failure and four were tracheostomized due to prolonged mechanical ventilation. severe complications were frequent, highlighting acute renal failure in patients ( . %), of which two required renal replacement therapy; cardiac failure or cardiogenic shock in eight patients ( . %); and ards in seven cases ( %) (two of them in patients with bacterial coinfection) ( table ). three patients who developed ards were younger than years ( , and years, respectively) without major comorbidities or bacterial coinfection. all of them underwent invasive mechanical ventilation due to acute respiratory failure (one had coinfection with hpiv ). the main clinical and epidemiological characteristics of the patients are summarized in the supplementary material (additional file : table s , additional file : table s ). the majority of the patients ( . %) had lymphocytopenia (< /ml) at admission ( our study gives new insights on the molecular epidemiology of hmpv pneumonia admitted to the icu over years. hmpv was consistently detected in cap admitted to the icu, with an annual incidence ranging . - case/ , inhabitants older than years per year. molecular characterization of hmpv revealed group dominance of subgroup b. hmpv infection presented seasonal distribution, with / of cases detected in late winter-early spring each year. the % of the studied patients were younger than years without comorbidities. hmpv cap often presented as acute respiratory failure with bilateral opacities and half of icu subjects underwent mechanical ventilation. lymphocytopenia and pleural effusion were common at admission. plasma procalcitonin was a sensitive tool to identify coinfection with bacteria ( %), which contributes to antimicrobial stewardship. these findings suggest the need to implement hmpv diagnosis tests in subjects with cap developing acute respiratory failure. two out of three patients of this study had shock at admission, half of them underwent mechanical ventilation, one out of four developed ards and one out of seven died during the clinical course, suggesting that hmpv is responsible for scap in adults. these data are concordant to that observed in the only study with a wide range of patients with hmpv infection in critically ill patients, in which % of the patients required mechanical ventilation, % developed ards and the mortality was % [ ] . moreover, there are sporadic reports of - patients with hmpv infection acquired in the community and acute respiratory failure who required icu admission [ ] [ ] [ ] . in a large prospective study of icu patients requiring invasive mechanical ventilation, hmpv was more frequently detected in patients admitted by severe respiratory infection than in patients with other causes, suggesting a causal role of hmpv in the development of severe respiratory infection [ ] . most of the patients of this study had major comorbidities at admission, mainly chronic respiratory failure and immunosuppression, being those patients and the elderly the most susceptible to develop severe hmpv infections [ , , ] . however, % of the patients were younger than years old and one out of three did not have major comorbidities, being similar to cap related to other etiologies. interestingly, three patients ( . %) were young adult patients without comorbidities and without bacterial coinfection that developed ards pointing out a main role of hmpv in the etiology of severe respiratory infections requiring mechanical ventilation. in the cohort of patients of hasvold et al. [ ] , % of the patients had only minor comorbidities and were not immunosuppressed. one out of four episodes of severe acute respiratory infection was coinfected with bacteria, similar to that observed in other series [ , ] . streptococcus pneumoniae, one of the bacterial species most frequently involved in post-viral super-infections [ ] , was the main isolated bacterial pathogen. in these episodes, procalcitonin has been reported to discriminate between viral episodes and those with bacterial coinfection [ ] , in contrast with crp. some studies have recommended different cutoff points of procalcitonin to discontinue early antibiotic therapy in patients with community-acquired therapy, being . ng/ml and, mainly . ng/ml the most recommended [ , ] . none of the patients with documented bacterial coinfection in this study had a procalcitonin level lower than ng/ml which supports the early discontinuation of antibiotic therapy in this group of patients with low plasma levels of procalcitonin. the results of this study, about procalcitonin plasma determinations, could help to develop personalized medicine in patients with cap, helping physicians to early discrimination between viral or bacterial pneumonia and antimicrobial stewardship [ ] . three different genotypes of hmpv were associated with severe cap requiring icu admission, which supports that all of them are able to cause severe infections in adult patients. the low number of cases of the three different hmpv lineages, the presence of coinfections and the retrospective nature of the study made impossible to analyze the clinical pattern and the evolution of the patients based on the genotype of the infecting hmpv. however, to date, there are no significant differences in the evolution or clinical manifestation between different genotypes of hmpv in adults in the outpatient setting [ ] . this study has some limitations and therefore, the results should be evaluated cautiously. the hmpv infection was diagnosed by oropharyngeal swab samples more than in low respiratory tract samples, mainly in non-intubated patients. the detection of a viral pathogen in respiratory samples of a patient with acute respiratory infection can be coincident and not related to icu admission. the retrospective design of the study can underestimate the actual incidence of hmpv infection because some patients admitted because of acute respiratory infection could not be investigated for viral etiology. however, from the influenza pandemics, nasopharyngeal swab samples with respiratory viral detection are routine of care being collected in the % of patients with scap admitted to icu. finally, three different molecular techniques were used, with potential selection bias due to the differences in sensitivity of these techniques. in conclusion, our study confirms that hmpv, a respiratory virus causing bronchiolitis and pneumonia in children, was associated with severe cap requiring icu admission among elderly patients or patients with comorbidities, but also in healthy young subjects. these patients often underwent mechanical ventilation with long icu and hospital stays, associated with elevated health resource consumption. the results of this study agree with recent observations [ ] suggesting a shift in the paradigm of severe pneumonia, recommending that viral infection (and specifically hmpv) should be ruled out when complicated with acute respiratory failure. while one out of four patients showed pneumococcal coinfection, plasma procalcitonin levels helped to implement antimicrobial stewardship. additional file : table s . main characteristics of immunocompetent adult patients admitted to the intensive care unit due to a severe community-acquired pneumonia associated with human metapneumovirus infection (guipuzcoa, basque country, spain, - ). table s . main characteristics of immunosuppressed adult patients admitted to the intensive care unit due to a severe community-acquired pneumonia 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severe pneumonia requiring intensive care unit admission the role of human metapneumovirus in the critically ill adult patient infection biomarkers in primary care patients with acute respiratory infections-comparison of procalcitonin and c-reactive protein serum procalcitonin measurement and viral testing to guide antibiotic use for respiratory infections in hospitalized adults: a randomized controlled trial acute respiratory distress syndrome: the berlin definition validation of a combined comorbidity index seasonal distribution and phylogenetic analysis of human metapneumovirus among children in osaka city respiratory viruses in invasively ventilated critically ill patients-a prospective multicenter observational study postviral complications. bacterial pneumonia procalcitonin (pct) levels for ruling-out bacterial coinfection in icu patients with influenza: a chaid decision-tree analysis effect of procalcitonin guided guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the pro-hosp randomized controlled trial procalcitonin guidance of antibiotic therapy in community acquired pneumonia: a randomized trial towards precision medicine in sepsis: a position paper from the european society of clinical microbiology and infectious diseases the role of human metapneumovirus genetic diversity and nasopharyngeal load on symptom severity in adults lv made substantial contribution to the conception and design of the work, the acquisition, analysis and interpretation of the data and has drafted the work. it made substantial contribution to the conception and design of the study, analysis and interpretation of the data. dv, mm, jr and gc made substantial contributions to the interpretation of the data and substantively revised it. all authors read and approved the final manuscript. the authors declare that there has not been any source of funding for the research. the datasets supporting the conclusions of this article are included within the article (and its additional file). the study was approved by the ethics committee for clinical research of the health area of gipuzkoa (spain). informed consent was waived due to the retrospective nature of the study. not applicable. the authors declare that they have no competing interests. key: cord- -wb n w authors: nieman, gary f.; gatto, louis a.; andrews, penny; satalin, joshua; camporota, luigi; daxon, benjamin; blair, sarah j.; al-khalisy, hassan; madden, maria; kollisch-singule, michaela; aiash, hani; habashi, nader m. title: prevention and treatment of acute lung injury with time-controlled adaptive ventilation: physiologically informed modification of airway pressure release ventilation date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: wb n w mortality in acute respiratory distress syndrome (ards) remains unacceptably high at approximately %. one of the only treatments is supportive: mechanical ventilation. however, improperly set mechanical ventilation can further increase the risk of death in patients with ards. recent studies suggest that ventilation-induced lung injury (vili) is caused by exaggerated regional lung strain, particularly in areas of alveolar instability subject to tidal recruitment/derecruitment and stress-multiplication. thus, it is reasonable to expect that if a ventilation strategy can maintain stable lung inflation and homogeneity, regional dynamic strain would be reduced and vili attenuated. a time-controlled adaptive ventilation (tcav) method was developed to minimize dynamic alveolar strain by adjusting the delivered breath according to the mechanical characteristics of the lung. the goal of this review is to describe how the tcav method impacts pathophysiology and protects lungs with, or at high risk of, acute lung injury. we present work from our group and others that identifies novel mechanisms of vili in the alveolar microenvironment and demonstrates that the tcav method can reduce vili in translational animal ards models and mortality in surgical/trauma patients. our tcav method utilizes the airway pressure release ventilation (aprv) mode and is based on opening and collapsing time constants, which reflect the viscoelastic properties of the terminal airspaces. time-controlled adaptive ventilation uses inspiratory and expiratory time to ( ) gradually “nudge” alveoli and alveolar ducts open with an extended inspiratory duration and ( ) prevent alveolar collapse using a brief (sub-second) expiratory duration that does not allow time for alveolar collapse. the new paradigm in tcav is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. this novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. the outcome of this approach is an open and stable lung with reduced regional strain and greater lung protection. globally more than three million patients per year develop acute respiratory distress syndrome (ards), accounting for % of all intensive care unit (icu) admissions. in the united states, up to , patients a year are diagnosed with ards and , of these patients die [ ] . current ards treatment is supportive: protective mechanical ventilation, typically using lower tidal volume ventilation (vt) and low-moderate positive end expiratory pressure (peep) [ ] . unfortunately, current protective ventilation strategies have not lessened ards mortality rate [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the determinant of vili is not the "mode" of ventilation, but the way parameters of the mechanical breath are set and combined. the goal of any protective mechanical breath should be maintaining functional residual capacity and increasing lung homogeneity. in this paper, we review the pathophysiology of ards in the microenvironment and identify how changes in alveolar micromechanics predispose the lung to a secondary vili. understanding how ards alters the dynamic alveolar inflation physiology enables us to adjust the mechanical breath profile (mb p -all airway pressures, volumes, flows, rates and the time at inspiration and expiration at which they are applied) necessary to minimize vili [ ] . variants of the airway pressure release ventilation (aprv) mode have been used for decades with many combinations of settings (fig. ) . in this review, we discuss the physiological impact of the time-controlled adaptive ventilation (tcav) method on ards-induced abnormal alveolar mechanics, efficacy in both translational animal models and in a retrospective clinical analysis. acute respiratory distress syndrome pathophysiology current falls into three categories: (a) normal nondependent tissue, (b) severely injured and collapsed dependent tissue, and (c) unstable tissue located between these two tissue types [ , ] . efforts to minimize vili, block progressive acute lung injury (ali), and reduce ards mortality have resulted in two current approaches: ( ) the ardsnet low vt (lvt) method is intended to protect the non-dependent normal lung tissue from overdistension (od) and reduce alveolar recruitment/ derecruitment (r/d) with positive end expiratory pressure (peep), while resting severely injured tissue by allowing it to remain collapsed throughout the ventilation cycle [ ] . however, this strategy has not further reduced ards mortality [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . this suggests that our understanding of ards pathophysiology remains [ ] all using the airway pressure release ventilation (aprv) mode but with different methods: a stock et al. used a cpap phase that encompassed % of each breath, a release phase of . s and a respiratory rate (rr) of /min [ ] ; b davis et al. decreased the respiratory rate by prolonging both the cpap and release phase [ ] ; c gama de abreau et al. adjusted their cpap and release phase to values typical of a conventional breath [ ] ; d roy et al. minimized the release phase and extended cpap to occupy % of each breath, typical of the time-controlled adaptive ventilation (tcav) method [ ] . although these studies all used the aprv mode, each differs significantly in the application methods used to set the mode incomplete, particularly in the lung microenvironment [ , ] . indeed, the concept that the pulmonary parenchyma falls into three crudely differentiated categories according to the gravitational axis is being challenged. the current understanding is that open and collapsed tissues are not delineated into compartments, but are rather intermingled throughout the entire lung [ ] [ ] [ ] [ ] [ ] . the unchanged mortality associated with the lvt method may also reflect the fact that maintaining lung tissue collapse ("resting") may not be protective [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the atelectatic lung does not exchange gas, is susceptible to pneumonia, and may ultimately lead to collapse induration and fibrosis with the inability to re-inflate or epithelialize the airspace [ ] [ ] [ ] . using conventional ventilation strategies, the ola has not been shown to reduce alveolar r/d-induced atelectrauma [ , ] or improve survival [ ] . in a recent rct, the ola with maximal recruitment strategy and peep set to best compliance resulted in increased mortality [ ] . however, the lack of significant differences in compliance and driving pressure (∆p) between groups suggested that ( ) the lungs had not been well recruited, which is essential for the ola strategy to be effective; ( ) the lungs were overdistended by excessive strain following the maximal recruitment; or ( ) the chosen peep was not optimal to stabilize the newly recruited lung. other research has shown [ ] that ola could not be attained using peep up to cmh o and plateau pressure (pplat) limited to cmh o. while ola is theoretically lung protective, traditional recruitment maneuver (rm) + peep methods may not provide sustained recruitment, stability, and homogeneity [ , , [ ] [ ] [ ] . more recent studies suggest that the lung pathology compartmentalized by gravity (i.e., normal lung tissue adjacent to acutely injured tissue) is incorrect and that regional lung strain and inflammation throughout the entire lung is the main driver of vili [ , [ ] [ ] [ ] [ ] [ ] [ ] . regional strain is caused with each breath by ( ) alveolar and alveolar duct r/d [ ] [ ] [ ] [ ] [ ] [ ] [ ] and ( ) stress-multiplication (s-m), which cause injury to open lung areas adjacent to collapsed or edema-filled tissue [ , , [ ] [ ] [ ] [ ] [ ] . retamal et al. used ct scans to generate volumetric strain maps revealing highly heterogeneous regional strains (caused by alveolar r/d and s-m), which suggests that there may not be a safe threshold for low vt [ ] . cereda et al. hypothesized that vili is not caused by overdistension of normal lungs, but rather develops in multiple areas of excessive regional strain located throughout the lung and caused by the primary insult [ ] . they showed that tissue adjacent to the primary lesion was most susceptible to secondary vili, an outcome supported by dynamic modeling of interdependent parenchyma during ali [ ] . this suggests that to effectively reduce vili at the bedside, the clinician needs to know how to adjust ventilator settings (e.g., vt, pplat, peep, inspiratory and expiratory duration) to reduce r/d and s-m [ ] [ ] [ ] . synchrotron phase-contrast imaging can measure r/d at acinar length scales over short time frames and has demonstrated that lung collapse in the microenvironment differs between normal and acutely injured lungs [ ] [ ] [ ] [ ] . scaramuzzo et al. first measured tissue collapse in the microenvironment of the normal lung with graded reductions in peep. they assessed the numerosity (asnum) and dimension (asdim) of airspaces during lung deflation and found that the primary mechanism by which the lung loses volume was reduced asnum secondary to alveolar and small airway derecruitment [ ] . in a subsequent paper, scaramuzzo showed in an ards model that the mechanism of lung deflation was reduced asdim, which differs from the mechanism of normal lung deflation (asnum) [ ] . broche et al. showed that "compliant collapse", which is described "as a structural collapse of the airway wall along a certain length" is the primary mechanism of airway closure in the acutely injured lung [ ] . "compliant collapse" suggests that fluid movement in the microenvironment would play a role in airway collapse and reopening. thus, the function of time during inspiration and expiration, and the opening and closing pressures, would be key components in keeping the lung open and stable [ ] . this work underscores the merits of an extended inspiratory duration and a brief expiratory duration to improve alveolar recruitment and stability in a rat ards model [ ] , lung protection in a neonatal piglet model [ ] , and reduced ards incidence and mortality in trauma patients [ ] . we postulate that as the lung opens, the increase in parenchymal tethering of airways [ ] and alveolar interdependence [ ] reduce lung pathology as a power-law function. hamlington et al. have shown that progressive lung injury advances in power-law fashion where alveolar r/d (atelectrauma) caused the initial holes in the epithelium and that high airway pressure (volutrauma) greatly expands these holes in a power-law or rich-get-richer fashion [ ] . lung protection also arguably follows a power-law function with reestablishment of parenchymal tethering, alveolar interdependence, and surfactant function all working together to accelerate recruitment and stabilization of adjacent tissue. alveoli are often misunderstood as elastic and modeled as rubber balloons with immediate size changes (volumetric distortion or strain) with application or removal of pressure (physical stress) during inspiration and expiration [ ] . in reality, alveoli behave in a viscoelastic rather than an elastic manner [ , [ ] [ ] [ ] . viscoelastic systems exhibit a time-dependent strain and can be conceptualized by the spring-and-dashpot model (fig. ) [ ] . figure illustrates the strain/time curve of elastic (spring), viscous (dashpot), and viscoelastic (spring-and-dashpot) behaviors. since the lung opens and collapses as a viscoelastic system, we use the spring and dashpot to illustrate lung recruitment during inspiration and derecruitment during expiration. the initial rapid opening or collapse (strain) of lung tissue followed by a continual opening or closing over an extended period time ( - s) is important. viscoelastic behavior of alveolar opening and collapse begins only after the critical opening or collapse pressure for that alveolus is reached. before these critical pressures are obtained, there is no alveolar strain. however, the opening and closing pressures are not static; instead, they are dependent upon the level of surfactant deactivation and the degree of mechanical interdependence between adjacent alveolar walls and parenchymal tethering on the walls of small airways [ ] . the original computational model of r/d by ma and bates was based on symmetrical bifurcations of the airway tree with each branch having an individual critical opening and collapse pressure [ ] . however, this computational model no longer supported the new biological evidence on r/d at the acinar level. an alveolar interdependence component was added to the model such that the closure of a unit will impact the critical opening and collapse pressures of adjacent units [ ] . fluid movement in the microenvironment during airway collapse and reopening suggests that the pressures necessary for opening and collapse are also a function of the time at which they are applied [ ] . thus, a long inspiratory time with a short expiratory time would open more alveoli and prevent more alveolar collapse, as compared to the same airway pressures applied for shorter or longer amounts of time [ ] . since alveoli recruit as a viscoelastic system, once critical opening and collapse pressures are reached, the longer the inspiration (fig. -red hold) , the more lung tissue recruited with each breath [ , [ ] [ ] [ ] [ ] . similarly, the shorter the expiratory duration (red release), the less lung tissue that will collapse. furthermore, the sustained inspiratory time causes both creep and stress relaxation, the most likely mechanism of which is redistribution of gas within the lung or opening of collapsed alveoli [ ] . we postulate that this information can be used to design an mb p that will open and stabilize the acutely injured lung. the longer the inspiratory time, the more alveoli recruited. we previously quantified in vivo alveolar recruitment in real-time in a rat ards study that involved mathematical modeling. initial recruitment after the applied breath did not begin until after the first second, followed by a rapid recruitment ( - s). the majority of recruitment occurred in s with continued gradual recruitment over the subsequent s (fig. ) [ ] . the absence of any inflation for the first second has clinical significance since inspiratory time in most conventional ventilator settings is . - . s. a brief inspiratory time confines ventilation to proximal conducting/convective airways rather than allowing the time-dependent gas distribution to reach and facilitate diffusion in the distal airspace [ ] . other investigators using ct scans combined with mathematical modeling also support this temporal lag in alveolar opening following an applied proximal airway pressure [ ] [ ] [ ] . the similarities between alveolar percent recruitment/time ( fig. ) coincide with the viscoelastic behavior strain/ time curves (fig. , inspiration-lung recruitment). derecruitment of alveoli is also viscoelastic in nature (fig. , expiration-lung derecruitment). the deflation strain/ time curve suggests that a ventilator strategy with a brief expiratory duration (red release) would minimize lung collapse, placing ventilation on the more favorable expiratory portion of the pressure-volume curve [ ] . there is no mechanistic evidence that current ola protocols using a rm and titrated peep actually achieve and sustain an open lung [ , , ] . the ardsnet method features a brief time at peak inspiration and an extended time at expiration (fig. , left) , producing an mb p that is antithetical to the tcav method (fig. , right) . conversely, the tcav method reconfigures time systems. an applied force (red arrows) generates a stress that results in a yield or strain once the force reaches critical opening pressure. upper left: the spring models elasticity with a rapid increase in strain leading to a plateau strain, which is distinctive of that spring. upper right: the dashpot models viscous strain, where movement of the dash progresses (dashed line) with flow of the fluid in the pot around the dash (brown arrows), which is distinctive of the viscosity of the fluid. bottom: viscoelastic behavior is modeled by the spring and dashpot, where force transfer from the spring to the dash results in a time-dependent strain with an initial rapid change in strain ( - s), which becomes gradual over time ( - s) . lung strain follows this behavior (fig. ) . bottom left: an extended inspiratory time (hold) optimizes lung recruitment once critical opening pressure is reached. bottom right: a short expiratory time (release) minimizes lung derecruitment if it is sufficiently fast to prevent reaching the critical collapse pressure (see figure on next page.) allocation to extend inspiration using a continuous positive airway pressure phase (cpap phase) with a brief (sub-second) release for exhalation (release phase). open valve cpap is used rather than closed valve to allow the patient to spontaneously inhale or exhale with little added resistance at any time in the breathing cycle. the short expiratory time does not allow the expiratory flow to reach zero flow, and therefore, the alveolar pressure is always above the set expiratory pressure (p low ), which itself is always set at cmh o. the cpap phase initiates before the lung fully depressurizes (fig. , right) , maintaining a positive end expiratory pressure determined by the peak expiratory flow, the expiratory duration, and the compliance of the respiratory system. the gas volume released (vr) during the release phase is analogous to vt in that it equals the volume delivered during the cpap phase (we use vt in place of vr in this review for consistency). however, tcav does not aim to achieve a target vt, but rather the vt changes depending on the release time (t low ), which is adjusted by changes in respiratory system compliance (c rs ): ↓c rs = ↓vt and ↑c rs = ↑vt alveolar recruitment is not only a function of the amount of pressure applied to the lung, but also of the time during which the pressure is applied because alveoli open and collapse as a viscoelastic system (fig. , viscoelastic behavior) . alveolar volume change is further influenced by alveolar micro-anatomy, including parenchymal tethering and shared alveolar walls, establishing alveolar interdependence. all the above components play an important role in alveolar recruitment and derecruitment [ , , [ ] [ ] [ ] . thus, the longer airway pressure is applied, the more alveoli recruited (fig. , viscoelastic behavior) [ ] . this time-dependent recruitment has been described by suki et al. as the "avalanche theory" of lung inflation [ ] . we conducted histological measurements of terminal airspace in a rat ards model [ ] and reported a redistribution of gas from alveolar ducts into alveoli with tcav, but not with a volume-controlled mode. stress relaxation occurs during the cpap phase because there is sufficient time for alveoli to be recruited. we postulate that gas is transferred from the more elastic ducts (fig. , viscoelastic behavior-rapid initial strain) into the more viscous alveoli (fig. , viscoelastic behavior-slow progressive strain over time) during the extended cpap phase. by comparison, the ardsnet brief inspiratory time (fig. , left, duration of inspiration) method would not effectively recruit viscoelastic alveoli, allow time for tissue creep, or result in redistribution of gas from the ducts into the alveoli [ , ] . this is supported by studies indicating that the ola, which uses occasional rms combined with a brief inspiratory duration (fig. , left) , has not been shown to reduce mortality. the likely reason for this lack of efficacy is that neither rms nor the brief fig. the ardsnet method using the volume assist-control ventilation mode (left) has an i:e ratio of : , which directs a short inspiration and a long expiration, and peep is arbitrarily set. conversely, the tcav method (right) has an i:e ratio of : , which directs a long inspiration (cpap phase) and a short expiration (release phase), not allowing the lung to fully depressurize and resulting in a time-controlled peep (tc-peep, red dashed line). time controlled-peep (tc-peep) is adaptive (not arbitrary) because it is determined in real-time according to compliance, which is measured in the preceding breath by the slope of the expiratory flow curve (slope fe ) (red arrowhead on right) (fig. ) inspiratory duration effectively opens the lung; therefore, alveolar heterogeneity and regional strain were not eliminated [ , , ] . to normalize the alveolar duct to alveolar volume distribution in the acutely injured lung, it is necessary to use a combination of an extended time at inspiration (cpap phase) and short expiratory duration (release phase) (fig. , right) . the physiologic impact of tcav on lung recruitment over time in a brain-dead organ donor is depicted in fig. a , top. displayed respiratory system compliance (c rs ), driving pressure (∆p = vt/c rs ), and vt measurements are after initial transition of the brain-dead donor to tcav (tcav = h) and then (tcav = h) and (tcav = h) hours on tcav. the prolonged inspiratory time (fig. , right) gradually "nudges" open the lung and normalizes gas distribution within the alveoli and ducts (fig. a -blue collapsed lung tissue converting to open tan tissue) and the brief expiratory time prevents these newly opened alveoli from re-collapsing (fig. , right) [ ] . although the ∆p was slightly elevated ( . cmh o) when tcav was first applied (t ) due to the low c rs ( ml/cmh o), it remained within the safe range due to the low vt ( . ml/kg). as the lung recruited over time, the vt increased (t = . ml/kg) without increasing ∆p, which fell into the normal lung range ( . cmh o) due to increased c rs ( ml/kg). continual reduction in ∆p occurred because c rs increased (t = ml/ cmh o) as the lung fully opened and ∆p fell into the normal range ( . cmh o) (fig. a, top) with a vt of . ml/ kg. these data indicate how the vt can only increase if c rs increases, which personalizes the vt to the pathophysiology of the patient's lung in real-time and normalizes the tidal volume to lung volume (fig. a, top) . figure b , bottom depicts the ventilator screen and the chest radiograph (cxr) from a brain-dead donor initially on controlled mechanical ventilation (cmv) and then converted to tcav. the progressive changes in ∆p and cxr at (tcav = h), (tcav = h) and (tcav = h) hours on tcav are displayed. the progressive decrease in ∆p as the lung recruits is identified by the reaeration of the lung on cxr. these data suggest that an extended cpap duration for a period of hours will "nudge" alveoli open with each breath, reducing c rs and allowing ventilation at a low ∆p even with a vt higher than ml/kg. the lung becomes time and pressure dependent when acutely injured, such that it will quickly collapse at atmospheric pressure [ , [ ] [ ] [ ] . in animal ards models, the majority of lung collapse occurred in the first s of exhalation with collapse as fast as . s [ ] . this suggests preventing collapse of alveoli with the fastest time constants, the expiratory duration must be less than . s. markstaller et al. had similar findings in an ards porcine model with lung collapse occurring in % of the lung within . s [ ] . lachmann was one of the first to suggest that stabilizing alveoli with heterogeneous collapse time constants could be accomplished by dramatically shortening expiratory time [ ] . together, these studies suggest it is possible to stabilize alveoli with fast collapse time constants by using a brief expiratory time [ , , ] . the slope of the expiratory flow curve (slope fe ) allows breath-by-breath assessment of changes in c rs (fig. ) [ ] . with progressive ali, edema and loss of surfactant function increases lung recoil force, causing (see figure on next page.) fig. optimizing recruitment with tcav allows the lung to accommodate increased tidal volumes, without increases in driving pressure, due to a concomitant increase in compliance. a tcav-induced lung recruitment over time ( - h) in a brain-dead organ donor. driving pressure (Δp) was calculated as tidal volume (vt) divided by respiratory system compliance (c rs ). the adaptive nature of tcav delivers low vt ( . ml/kg at h) with lung collapse and low c rs , but adjusts vt over time (vt = . ml/kg at h, vt = . ml/kg at h) as the lung opens and c rs increases. notably, Δp actually decreased despite increasing vt (a). b evolution of driving pressure (Δp) and chest x-ray (cxr) over time: a cmv (conventional mechanical ventilation) on a brain-dead organ donor ( kg) with baseline ventilator settings: vc-ac, vt , rate , peep cmh o with peak pressure cmh o, vt . ml/kg/predicted body weight (pbw), and Δp ml/cmh o. chest x-ray showed severe bilateral infiltrates. tcav = h: h after transition to tcav with settings: cpap phase pressure = cmh o, release set pressure = cmh o, cpap time = . s, release phase duration = . s. note the lower vt of ml ( . ml/kg/pbw), which gradually increased from a vt of . ml/kg/pbw when first transitioned to tcav (data not shown); both vts using the tcav protocol are lower than those on the conventional mode (cmv = ml, . ml/kg/pbw). the cxr demonstrates radiographic clearing of densities with significant recruitment and a reduction in Δp from to ml/cmh o. tcav = h: h on tcav, a new chest radiograph for line placement indicated continued recruitment, and the cpap phase pressure was subsequently decreased to cmh o. in addition, the angle of the expiratory flow curve became less acute (fig. ) , and the release phase duration was increased to . s. the cpap time was increased to . s because ventilation had improved. despite a lower p high , the vt continued to increase as did an improvement in c rs . the continued radiographic clearing of densities and reduction in Δp fell to ml/cmh o despite continued vt increase. tcav = h: the cpap phase pressure was further decreased to cmh o due to continued recruitment (cxr) with a Δp of ml/cmh o. the lungs and the heart, liver, and both kidneys from this organ donor were all successfully transplanted rapid lung collapse and decreased c rs . the collapse rate of the lung is manifested as a change in the slope of the expiratory flow curve (slope fe ), a measure of lung recoil, which is determined by c rs and both turbulent and viscous resistances [ ] . brody demonstrated that ( ) lung c rs could be calculated if both of these resistances are known; ( ) dynamic c rs must be a constant, independent of volume; and ( ) the inertia of the chest-lung system is negligible [ ] . the brief release phase is passive without muscular effort or added external resistance (i.e., peep) such that the slope fe can be used as a bedside monitor to analyze the mechanical properties of the respiratory system on a breath-to-breath basis [ ] . the release phase is protocolized using the tcav method for the expiratory flow to terminate (e ft ) at % of the expiratory flow peak (e fp ) (e fp × % = e ft ) (fig. a, b) [ ] . the formula e fp × % = e ft was first identified empirically at the bedside to be effective at stabilizing the lung [ ] and has been subsequently shown to be most effective at maintaining open and stable alveoli [ ] , normalizing alveolar/alveolar duct volume distribution [ ] , and resulting in homogeneously ventilated alveoli [ ] . in the example presented in fig. b , e fp is − l/min, so the expiratory flow is terminated (e ft ) at − . l/min (− l/min × % = − . l/min). to accomplish this at the bedside, the clinician sets the ventilator to terminate the expiratory flow when it reaches . l/min (fig. , right) , and the cpap phase is restored (fig. , right) . although slope fe is not directly measured, fig. personalizing the release phase using the slope of the expiratory flow curve (slope fe ). the release phase becomes briefer, directed by the slope fe with lung injury severity. a normal lung release phase is . s, with moderate ards of . s and severe ards of . s, all directed by changes in the slope fe . b the release phase duration is calculated by expiratory flow terminating (e ft ) at % of the expiratory flow peak (e fp ) (red arrow head). in this example, the e fp = − l/min, so flow will be terminated (e ft ) at − . l/min (− l/min × % = − . l/min). although the e ft is always at . l/min in our example, the release phase duration varies ( . , . , . s) due to changes in the slope fe (a, b) . we did not directly measure the slope of the expiratory flow curve, but by terminating expiration at % of the e ft , changes in the slope change the expiratory duration (a, b) . thus, the release phase is both personalized and adaptive as the patient's lungs become better or worse using the tcav method. c expiratory flow/ time graphics on a ventilator monitor from a brain-dead organ donor meeting berlin criteria for severe ards. the release phase was set using the equation: e fp × % = e ft . the slope fe when tcav was initially applied was . °, resulting in a release phase of . s. twenty-four hours on tcav and the slope fe increased to . °, resulting in a release phase of . s. the spike in the expiratory flow curve is an artifact due to compression of gas in the ventilator circuit variation in the slope causes a change in release phase duration: gradual slope = long release phase and steep slope = short release phase (fig. a, b, . , . , . s release phase times with changes in the slope fe ). figure c depicts two airway flow/time curves with the slope fe circled and the angle measured on the ventilator monitor in a brain-dead donor. the top curve shows the initial application of tcav, and the bottom curve is h later. with a steep slope ef , expressed as an angle ( . °), the expiratory time is short (t low . s), and as the slope ef increases (angle goes from . º to . °), the expiratory duration increases (t low . s). this illustrates that the duration of the release phase changes with changing lung pathology and thus is personalized and adaptive as the patient's lung mechanics becomes better or worse (fig. a, b ). with cpap, the vt is directly related to c rs (fig. a, top) . the adaptive quality of the tcav breath allows for unique personalization of vt based on changes in lung physiology in contrast to the prevailing "one size fits all" ml/kg method [ ] . further, the tcav method maintains a low Δp since vt decreases as c rs decreases (figs. a, top and ). figure presents gross lung photographs and the corresponding lung compliance (c rs ), tidal volume (vt), and driving pressure (Δp) calculated from a previously published paper [ ] . the animal model utilized was a clinically applicable porcine peritoneal sepsis and gut ischemia/ reperfusion (ps + i/r) ards model [ ] . two groups of animals were studied: ( ) ardsnet low vt (lvt) method applied after the animals desaturate and ( ) the tcav method applied immediately following ps + i/r injury. the time post-ps + i/r injury that these two protocols were applied matched the time of application on patients clinically (i.e., ardsnet method is applied to patients after oxygen desaturation [ ] and tcav is applied immediately upon intubation [ ] ). in the ardsnet group, c rs continually decreased over the -h study period, whereas in the tcav group, c rs remained similar to baseline at t (fig. c) . the Δp in the tcav group remained in the normal range even with elevated vt ( ml/kg) because c rs also increased (fig. d) . gross photos indicate that the tcav method (fig. a ) maintained an open homogeneously ventilated lung without edema, whereas the ard-snet method (fig. b) allowed the lung to develop severe atelectasis and both intra-lobule and airway pulmonary edema. given that the inspiration:expiration (i:e) ratio for tcav is approximately : , co retention could reasonably be a concern. because the tcav method is such an effective lung recruitment tool, there is seldom an issue with high blood levels of co once the lung is fully recruited. once recruited, there is a large surface area for co diffusion and thus high concentrations of co can be exhaled during the short release phase. the tcav method can be applied preemptively as soon as the patient is intubated, never giving the lung a chance to collapse and eliminating any problems with co retention [ ] , thus minimizing the risk of hypercapnia and eliminating the need for extracorporeal venovenous co removal (ecco r). in addition, if the patient is adequately hydrated, there is no negative impact on lung perfusion since lung recruitment reestablishes normal frc, which reduces pulmonary vascular resistance and right heart afterload [ , ] . no human rcts have yet utilized the tcav method, but several recent rcts have approximated many of the settings. zhou et al. first evaluated patients with a p/f less than mmhg who were intubated for less than h and randomized to receive either ardsnet lvt or aprv with tcav-like settings [ ] . the aprv group demonstrated a significant decrease in number of days on mechanical ventilation (from to ), length of icu stay , tracheostomy requirement ( . % to . %), and a . % absolute decrease in mortality ( . % to . %, p = . ), although the study was not sufficiently powered to show a difference in mortality. ganesan et al. conducted an rct using aprv and examined children under years old with ards who had been intubated for less than h and were randomized to receive either standard lvt strategy or aprv [ ] . unlike the zhou trial, the aprv arm performed significantly worse, necessitating early trial termination. the investigators, however, introduced two significant and synergistically harmful changes to the tcav protocol: setting and adjusting the p high pressure of the cpap phase based on vt and improper regulation of spontaneous breathing. by limiting p high to maintain a lower vt, the investigators never opened the lung to the point necessary to eliminate regional lung strain, the same mechanism hypothesized to explain the failed art rct. their initial mean airway pressure (pmaw) difference was only . cmh o despite setting p high at the pplat and then adding an additional cmh o. the authors even provide a table for guiding initial p high settings, which, based on the aprv arm's p/f ratio of mmhg, should have resulted in an initial pmaw difference closer to cmh o-an almost % increase from what was observed. lastly, hirshberg et al. conducted an rct in adults with acute hypoxic respiratory failure and attempted to keep the vt at about ml/kg. the study was stopped fig. gross lung photos with corresponding driving pressure (Δp), tidal volume (vt), and respiratory system compliance (c rs ) values over time [ ] . two protective mechanical ventilation strategies, the tcav method (a) and the ardsnet (lvt) method (b), were tested in a clinically applicable -h porcine ards model of peritoneal sepsis (ps) and gut ischemia/reperfusion (i/r) injury [ ] . the evolution of c rs , Δp, and vt with time in each group occurred over the -h study period (c, d). in the ardsnet lvt method group, Δp increased despite the reduction in vt because of worsening c rs . with the tcav method, Δp remained low despite vt = ~ ml/kg because c rs progressively increased (c, d). the personalized and adaptive vt based on lung c rs (i.e., high c rs = large vt and low c rs = small vt) was also seen in the brain-dead organ donor (fig. a) . gross lung photos illustrate that the tcav method (a) was lung protective, whereas the lvt method (b) resulted in severe acute lung injury. Δp was calculated retrospectively and was not in the publication by roy et al. [ ] early in part because the release volumes (i.e., vt) often exceeded ml/kg. using the tcav protocol an increasing vt indicates that the lung is reopening and is associated with improved crs, Δp, and cxr (see example, fig. b ). in addition, there was no evidence that the vt of ml/kg caused vili since there were no significant differences in pao /fio (p/f) ratio, sedation, vasoactive medications, pneumothorax, or outcome between groups [ ] . lastly, the t low was not set to a strict e fp × % = e ft . the aprv mode using different application methods has recently been shown in statistical reviews and meta-analyses of rcts to improved oxygenation, have a mortality benefit, and increase the number of ventilator-free days as compared to conventional ventilation strategies, without a higher risk of barotrauma or negative hemodynamic effects [ , ] . neither the current lung protect and rest nor ola ventilation strategies have been effective at reducing vili and ards-related mortality below that in the arma study. for a protective ventilation strategy to be effective, it must open and stabilize the lung. dynamic physiology of alveolar volume change suggests that the use of ventilation time can solve this heretofore intractable problem. the novel use of inspiratory and expiratory times to open and stabilize the acutely injured lung may accomplish the ola goals where traditional ventilation strategies have failed. specifically, the tcav method, which uses an extended time at inspiration to open alveoli and brief expiratory time to prevent alveolar re-collapse has been shown to effectively open and stabilize the lung in animal ards models. there is a sound physiological rationale for the efficacy of the tcav method, and deviations from this method may result in a significant loss of lung protection. the combination of basic science and clinical work has given this group a paradigm changing perspective. our approach focuses on veiled mechanisms that have been largely overlooked, such as understanding the time necessary for the alveolus to open or collapse or taking advantage of biological realities, such viscoelasticity, to manage the lung. the new paradigm in tcav is configuring each breath guided by the previous one, which achieves real-time titration of ventilator settings and minimizes instability induced tissue damage. this novel methodology changes the current approach to mechanical ventilation, from arbitrary to personalized and adaptive. the outcome of this approach is an open and stable lung, which reduces regional strain and provides greater lung protection. abbreviations ards: acute respiratory distress syndrome; vili: ventilator-induced lung injury; aprv: airway pressure release ventilation; frc: functional residual capacity; tcav: time-controlled adaptive ventilation; cpap: continuous positive airway pressure; tc-peep: time controlled-positive end expiratory pressure; t low : time at low pressure; t high : time at high pressure; p high : pressure at inspiration; p low : pressure at expiration; peep: positive end expiratory pressure; e ft : expiratory flow termination; e fp : expiratory flow peak; rct : randomized controlled trial; ola: open lung approach; mb p : mechanical breath pattern; ct: computerized axial tomography. acute respiratory distress syndrome: advances in diagnosis and treatment ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. the acute respiratory distress syndrome network epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in countries past and present ards mortality rates: a systematic review has mortality from acute respiratory distress syndrome decreased over time? a systematic review definition and epidemiology of acute respiratory distress syndrome current incidence and outcome of the acute respiratory distress syndrome lessons to learn from epidemiologic studies in ards outcome of acute respiratory distress syndrome in university and nonuniversity hospitals in germany mortality trends of acute respiratory distress syndrome in the united states from to outcomes of patients presenting with mild acute respiratory distress syndrome: insights from the lung safe study the -year evolution of airway pressure release ventilation (aprv) pressure-volume curve of total respiratory system in acute respiratory failure. computed tomographic scan study mechanical ventilation in adults with acute respiratory distress syndrome. summary of the experimental evidence for the clinical practice guideline looking beyond macroventilatory parameters and rethinking ventilator-induced lung injury airway pressure release ventilation reduces conducting airway micro-strain in lung injury visualizing the propagation of acute lung injury does regional lung strain correlate with regional inflammation in acute respiratory distress syndrome during nonprotective ventilation? an experimental porcine study stress distribution in lungs: a model of pulmonary elasticity alterations of mechanical properties and morphology in excised rabbit lungs rinsed with a detergent physiology in medicine: understanding dynamic alveolar physiology to minimize ventilator-induced lung injury alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis alveolitis and collapse in the pathogenesis of pulmonary fibrosis mechanical ventilation-associated lung fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome opening pressures and atelectrauma in acute respiratory distress syndrome does high peep prevent alveolar cycling? effect of lung recruitment and titrated positive endexpiratory pressure (peep) vs low peep on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial alveolar instability (atelectrauma) is not identified by arterial oxygenation predisposing the development of an occult ventilatorinduced lung injury effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on pao oscillations after saline lavage a fibre optic oxygen sensor that detects rapid po changes under simulated conditions of cyclical atelectasis in vitro unstable inflation causing injury: insight from prone position and paired ct scans deterioration of regional lung strain and inflammation during early lung injury tidal changes on ct and progression of ards lung inhomogeneities and time course of ventilator-induced mechanical injuries mechanical breath profile of airway pressure release ventilation: the effect on alveolar recruitment and microstrain in acute lung injury effect of airway pressure release ventilation on dynamic alveolar heterogeneity mechanisms of surface-tensioninduced epithelial cell damage in a model of pulmonary airway reopening the influence of non-equilibrium surfactant dynamics on the flow of a semi-infinite bubble in a rigid cylindrical capillary tube biomechanics of liquid-epithelium interactions in pulmonary airways tidal ventilation at low airway pressures can augment lung injury airway closure in acute respiratory distress syndrome: an underestimated and misinterpreted phenomenon alveolar volume-surface area relation in air-and saline-filled lungs fixed by vascular perfusion influence of forced inflations on the creep of lungs and thorax in the dog alveolar micromechanics in bleomycin-induced lung injury lung inhomogeneity in patients with acute respiratory distress syndrome micromechanics of alveolar edema local strain distribution in real three-dimensional alveolar geometries stress concentration around an atelectatic region: a finite element model acute respiratory distress syndrome never give the lung the opportunity to collapse preemptive mechanical ventilation based on dynamic physiology in the alveolar microenvironment: novel considerations of time-dependent properties of the respiratory system last word on viewpoint: looking beyond macroventilatory parameters and rethinking ventilator-induced lung injury regional behavior of airspaces during positive pressure reduction assessed by synchrotron radiation computed tomography the effect of positive end-expiratory pressure on lung micromechanics assessed by synchrotron radiation computed tomography in an animal model of ards dynamic mechanical interactions between neighboring airspaces determine cyclic opening and closure in injured lung individual airway closure characterized in vivo by phase-contrast ct imaging in injured rabbit lung ventilator-induced lung injury and lung mechanics limiting ventilator-associated lung injury in a preterm porcine neonatal model early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: a systematic review of observational trauma ards literature alveolar leak develops by a rich-get-richer process in ventilatorinduced lung injury lung tissue viscoelasticity: a mathematical framework and its molecular basis lung parenchymal mechanics lung parenchymal mechanics in health and disease modeling the complex dynamics of derecruitment in the lung respiratory mechanics in anesthetized paralyzed humans: effects of flow, volume, and time differential susceptibility of diaphragm muscle fibers to neuromuscular transmission failure lung mechanics. an inverse modeling approach nunn's applied respiratory physiology stress relaxation of the human lung the role of time and pressure on alveolar recruitment effect of different pressure levels on the dynamics of lung collapse and recruitment in oleic-acid-induced lung injury dynamics of lung collapse and recruitment during prolonged breathing in porcine lung injury what's new in respiratory physiology? the expanding chest wall revisited! intensive care med correlation between alveolar recruitment/derecruitment and inflection points on the pressurevolume curve ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial physiological effects of the open lung approach in patients with early, mild, diffuse acute respiratory distress syndrome: an electrical impedance tomography study airway-parenchymal interdependence. comprehensive micro-scale to meso-scale analysis of parenchymal tethering: the effect of heterogeneous alveolar pressures on the pulmonary mechanics of compliant airways a model of surfactant-induced surface tension effects on the parenchymal tethering of pulmonary airways avalanches and power-law behaviour in lung inflation viscoelastic properties of alveolar wall the effects of airway pressure release ventilation on respiratory mechanics in extrapulmonary lung injury early airway pressure release ventilation prevents ards-a novel preventive approach to lung injury predicting the response of the injured lung to the mechanical breath profile influence of inspiration to expiration ratio on cyclic recruitment and derecruitment of atelectasis in a saline lavage model of acute respiratory distress syndrome effect of tidal volume and positive end-expiratory pressure on expiratory time constants in experimental lung injury temporal dynamics of lung aeration determined by dynamic ct in a porcine model of ards open up the lung and keep the lung open mechanical compliance and resistance of the lung-thorax calculated from the flow recorded during passive expiration other approaches to open-lung ventilation: airway pressure release ventilation influence of state of inflation of the lung on pulmonary vascular resistance relation between lung volume and pulmonary vascular resistance early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome airway pressure release ventilation in pediatric acute respiratory distress syndrome: a randomized controlled trial randomized feasibility trial of a low tidal volume-airway pressure release ventilation protocol compared with traditional airway pressure release ventilation and volume control ventilation protocols airway pressure release ventilation in adult patients with acute hypoxemic respiratory failure: a systematic review and metaanalysis airway pressure release ventilation during acute hypoxemic respiratory failure: a systematic review and meta-analysis of randomized controlled trials airway pressure release ventilation: a new concept in ventilatory support airway pressure release ventilation regional lung aeration and ventilation during pressure support and biphasic positive airway pressure ventilation in experimental lung injury publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. drafting of manuscript-lag, gfn, nmh, bd. critical revisions-gfn, pla, js, sjb, mm, lag, ha, mk, nmh. all authors read and approved the final manuscript. salary support for gfn, js, sjb, from nih r hl . not applicable. not applicable. not applicable. pla, gfn, mks, and nmh have presented and received honoraria and/or travel reimbursement at event(s) sponsored by dräger medical systems, inc., outside of the published work. pla, gfn, and nmh have lectured for intensive care online network, inc. (icon). nmh is the founder of icon, of which pla is an employee. nmh holds patents on a method of initiating, managing, and/or weaning airway pressure release ventilation, as well as controlling a ventilator in accordance with the same, but these patents are not commercialized, licensed, or royalty-producing. the authors maintain that industry had no role in the design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript. key: cord- - prli s authors: vahedian-azimi, amir; bashar, farshid r.; khan, abbas m.; miller, andrew c. title: natural versus artificial light exposure on delirium incidence in ards patients date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: prli s nan we read with interest the study by smonig et al. on the impact of natural light (nl) exposure on delirium-associated outcomes in mechanically ventilated (mv) intensive care unit (icu) patients [ ] . in this single-center, prospective, observational study, the authors report an improvement in the secondary outcomes of hallucination incidence and haloperidol administration for agitation. no difference in delirium incidence or duration, mv duration, self-extubation, icu or hospital length-of-stay (los), or mortality was observed [ ] . we request clarification on whether the cumulative doses of haloperidol differed. smonig's findings differ from our observations. we have conducted a longitudinal cohort study of , icu patients with acute respiratory distress syndrome (ards) on mv from icus ( mixed, surgical, medical) from academic medical centers [ , ] . here, we report the results of a retrospective secondary analysis of patients from the mixed medical-surgical icus of two academic hospitals to assess the impact of nl exposure on delirium incidence. each icu had the same layout including beds; with adjacent windows allowing for nl (circadian pattern), and positioned m from the nearest window (artificial light: al). delirium was defined according to the dsm-iv-tr [ ] , and was assessed three times daily by the bedside nurse and researcher (kappa agreement coefficient . - . ) using the confusion assessment method for the icu (cam-icu) [ ] . we performed both unadjusted and adjusted logistic regression accounting for: year, diagnosis, age, sex, vital signs, illness severity (apache-ii score), development of ventilator-associated pneumonia, microbiology results, presence of an multiple drug resistant pathogens, mv duration, los (icu, hospital), and survival. we found that al patients had a . -and . times greater incidence of delirium by unadjusted and adjusted logistic regression, respectively. methodological differences in delirium definition, screening method and frequency, criteria for nl group, and population studied may contribute to the outcome heterogeneity across studies (table ) [ , [ ] [ ] [ ] [ ] . six studies utilized a validated delirium screening tool (table ) , whereas one did not [ ] , and one included (as a positive) any patient treated with haloperidol (regardless of screen result) [ ] . furthermore, two studies required a positive delirium screen on ≥ consecutive days to be classified as delirium [ , ] . moreover, the light exposure definitions vary considerably across studies. three studies compare patients in rooms with or without windows [ , , ] , whereas in two studies, all patients have nl exposure to differing degrees [ , ] . the assessed patient populations differ as well. whereas we found improved delirium outcomes in ards patients, who often have greater illness severity and longer icu los than the general icu patient population, no difference was observed in other icu populations [ , [ ] [ ] [ ] . our data suggest that further investigation in defined icu sub-populations may provide an opportunity to better identify those likely to benefit from nl exposure. such studies should capitalize on transparency using clear and reproducible of key variables including the definitions of delirium and nl exposure. based on the current level of evidence, it would be premature to discard a therapeutic role for nl exposure in critically ill patients. impact of natural light exposure on delirium burden in adult patients receiving invasive mechanical ventilation in the icu: a prospective study post-icu psychological morbidity in patients with ards and delirium impact of religiosity on delirium severity among critically ill shi'a muslims: a prospective multicenter observational study diagnostic and statistical manual of mental disorders (dsm-iv-tr) fourth edition (text revision) evaluation of delirium in critically ill patients: validation of the confusion assessment method for the intensive care unit (cam-icu) delirium and effect of circadian light in the intensive care unit: a retrospective cohort study effect of intensive care unit environment on in-hospital delirium after cardiac surgery do windows or natural views affect outcomes or costs among patients in icus? intensive care unit environment may affect the course of delirium publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. the authors that contributed to study design were ava, frb and acm. study implementation and data abstraction was performed by ava and frb. data analysis was performed by ava and acm. manuscript writing and revision were performed by acm amk, and ava. all authors read and approved the final manuscript. key: cord- -mupxzffk authors: diehl, j.-l.; piquilloud, l.; vimpere, d.; aissaoui, n.; guerot, e.; augy, j. l.; pierrot, m.; hourton, d.; arnoux, a.; richard, c.; mancebo, j.; mercat, a. title: physiological effects of adding ecco( )r to invasive mechanical ventilation for copd exacerbations date: - - journal: ann intensive care doi: . /s - - -y sha: doc_id: cord_uid: mupxzffk background: extracorporeal co( ) removal (ecco( )r) could be a valuable additional modality for invasive mechanical ventilation (imv) in copd patients suffering from severe acute exacerbation (ae). we aimed to evaluate in such patients the effects of a low-to-middle extracorporeal blood flow device on both gas exchanges and dynamic hyperinflation, as well as on work of breathing (wob) during the imv weaning process. study design and methods: open prospective interventional study in deeply sedated imv ae-copd patients studied before and after ecco( )r initiation. gas exchange and dynamic hyperinflation were compared after stabilization without and with ecco( )r (hemolung, alung, pittsburgh, usa) combined with a specific adjustment algorithm of the respiratory rate (rr) designed to improve arterial ph. when possible, wob with and without ecco( )r was measured at the end of the weaning process. due to study size, results are expressed as median (iqr) and a non-parametric approach was adopted. results: an improvement in paco( ), from ( ; ) to ( ; ) mmhg, p = . , and in ph, from . ( . ; . ) to . ( . ; . ), p = . , was observed after ecco( )r initiation and adjustment of respiratory rate, while intrinsic peep and functional residual capacity remained unchanged, from . ( . ; . ) to . ( . ; . ) cmh( )o and from ( ; ) to ( ; ) ml, p = . and p = . , respectively. wob measurements were possible in patients, indicating near-significant higher values after stopping ecco( )r: . ( . ; . ) versus . ( . ; . ) joules/min., p = . and . ( . ; . ) versus . ( . ; . ) joules/l, p = . . three patients died in-icu. other patients were successfully hospital-discharged. conclusions: using a formalized protocol of rr adjustment, ecco( )r permitted to effectively improve ph and diminish paco( ) at the early phase of imv in ae-copd patients, but not to diminish dynamic hyperinflation in the whole group. a trend toward a decrease in wob was also observed during the weaning process. trial registration clinicaltrials.gov: identifier: nct . chronic obstructive pulmonary disease (copd) is currently the fourth leading cause of death in the u.s. and is expected to become the third leading cause of death [ ] . value of non-invasive ventilation (niv) for severe ae-copd was formally demonstrated by randomized open access *correspondence: jean-luc.diehl@aphp.fr assistance publique -hôpitaux de paris, hôpital européen georges pompidou, service de médecine intensive -réanimation, rue leblanc, paris, france full list of author information is available at the end of the article clinical trials [ , ] . while the hospital mortality of patients successfully treated with niv has decreased over years, and is currently less than %, mortality in patients requiring imv after niv failure is close to % [ ] . among the techniques which could help to improve the prognosis of such patients, extracorporeal co removal (ecco r) seems to be a very promising approach [ , ] . however, most of the studies focused on ecco r in niv ae-copd patients, with the aim to prevent intubation [ ] [ ] [ ] or to provide an additional respiratory support after extubation [ ] . only a small number of imv copd patients were studied under ecco r, with the aim to facilitate extubation [ ] [ ] [ ] [ ] . ecco r was initiated early after intubation in studies [ , ] , while the delay between intubation and ecco r initiation was higher than days in another study [ ] . we preliminarily reported an ecco r-induced reduction in work of breathing and co production in such a setting [ ] , confirming and extending previous observations [ ] . in the present study, we hypothesized that the addition of ecco r at the early phase of imv could both improve gas exchanges and could also permit to diminish respiratory rate (rr), therefore, minimizing dynamic hyperinflation in ae-copd patients. beyond efficacy assessments, we also planned to describe the complications or adverse events associated with the technique, since bleeding and clotting complications were frequently reported in ae-copd patients [ ] . this interventional open prospective study was planned to recruit deeply sedated imv ae-copd patients in tertiary-level icus in france. an institutional ethic board (comité de protection des personnes ile-de-france vi, paris, france) approved the protocol (protocole ephebe p -id crb: -a - ). informed consent was obtained from patients' legal representatives. the study was prospectively registered in clinicaltrials.gov: identifier: nct . consecutive copd patients older than yrs. hospitalized for hypercapnic respiratory failure requiring imv were prospectively screened for inclusion in the study. inclusion criteria were: • ae of a known or suspected copd • intubation (whatever the reason for intubation which had to be specified) • mv since less than h. • persistent respiratory acidosis and hyperinflation, while the patients were deeply sedated and paralysed • written inform consent obtained from patient's legal surrogate criteria for persistent respiratory acidosis and hyperinflation were the combination of: ph < . , paco > mm hg and intrinsic peep (peepi) (endexpiratory occlusion) > cmh o, while on assist-controlled volume ventilation with the following settings: v t : ml/kg of predicted body weight (pbw), rr: /min., applied peep: cmh o, i/e ratio: / . non-inclusion criteria were as follows: body mass index (bmi) > kg/m , pao /fio < mm hg, history of haemorrhagic stroke, history of heparin-induced thrombocytopenia and any current severe bleeding. the protocol of the study was explained to the legal representatives and informed consent was obtained from patients legal representatives. when possible, the same explanations were further provided to the patient himself after full recovery, for obtaining a definitive post hoc written consent. the hemolung ® ecco r system (alung technologies, pittsburgh, pa) was used. it consists of an exchange cartridge (membrane surface . m ) which, in connection with a controller and tubing, ensures ecco r of about ml/min. at extracorporeal blood flow rates comprised between and ml/min. the vascular access is achieved by means of a double lumen . f central venous catheter. the maximum duration of use of the circuit, as specified by the manufacturer, is days. anticoagulation was achieved by the mean of continuous unfractionated heparin infusion aiming to obtain daily therapeutic antixa activities between . and . ui/ml. no systematic daily measurement of plasma free hemoglobin was performed during the study. the carescape r ventilator (general electric healthcare) was used allowing continuous measurement of the native lung's vco and serial measurements of the functional residual capacity (frc) (applied peep set at zero) or end-expiratory lung volume (eelv) (any positive applied peep) using the nitrogen washout/washin technique [ , ] . a nutrivent catheter (sidam, mirandola, italy) was inserted for esophageal pressure measurements, allowing the calculation of inspiratory work of breathing (wob) during the weaning process as previously described [ ] . figure illustrates the flowchart of the study. after inclusion in the study, we first calculate the target paco (paco target ) corresponding to a ph value of . , based on the henderson-hasselbach equation governing the relationship between paco , ph and bicarbonates plasma values. in cases of mixed respiratory and metabolic acidosis, any paco target below the normal paco value was replaced by the mmhg value. the second step of the study was to measure the physiological dead space (v d ) using the bohr-enghoff equation: v d /v t = (paco -p e co )/paco . the third step of the study was to start ecco r. after cannulation and initiation of the treatment, an increase in the sweep gas flow (using pure o ) generally up to l/min. induced a decrease in native lung's vco . we checked for stabilization of the latter, with a delay of h. the fourth part of the study was then to adjust rr for reaching paco target . for that purpose, we used the proportionality equation between alveolar ventilation, native lung's vco and paco : expressed as: assuming that v d was unchanged during the study. the fifth part of the study was to perform final measurements after waiting again for stability of the native lung's vco , with a further delay of h. if required, we adjusted the extracorporeal blood flow and/or sweep gas flow with the aim to keep unchanged the native lung's vco after the initial decrease. the primary outcome measure was peepi, measured during a prolonged expiratory pause at inclusion in the study and after initiation of ecco r combined with rr adjustment. we choose peepi as the primary outcome measure because we assumed that improvement in arterial ph and paco would be obvious and that the medical device would be powerful enough for achieving both improvements in respiratory acidosis and in dynamic hyperinflation. secondary end-points measured within the same time frame were: plateau pressure, peak pressure (ppeak), frc, paco , pao , arterial ph, hemoglobin saturation (sathbo ), extracorporeal vco , standard hemodynamic parameters. we also calculated v t /t e as a major determinant of dynamic hyperinflation. based on recorded files, wob at the end of the weaning process was measured just before extubation with and without ecco r under low pressure support ventilation as previously described [ ] . as a supplemental analysis, we also pooled the wob results of the present study with previously published results of pilot patients obtained using the same experimental design [ ] . ecco r-related adverse events were recorded during the whole icu-stay. this included severe hemolysis defined as a serum free hemoglobin level higher than mg/l and/or association to jaundice, hemoglobinuria or impaired renal function. time on ecco r, time on imv, length of stay in icu and in hospital and mortality at days were recorded. considering results obtained in preliminary pilot patients, we hypothesized a mean value of peepi at inclusion of cmh o along with an average reduction of cmh o of peepi after initiation of ecco r combined with rr adjustment (sd pooled = . -slightly below the average reduction). based on these assumptions, with evaluable patients, a paired t-test would reach a statistical power of % to conclude to the statistical significance of the difference before/after ecco r at the (two-sided) alpha level = . (nquery mot module). demographics and clinical characteristics of included patients at inclusion were described as follows: quantitative and qualitative variables were tabulated with medians, interquartile range (iqr) and range (min; max), and counts and proportions, respectively. we secondly described primary and secondary endpoints, at each time point, with the same statistical indicators. results are expressed in the results sections as median (iqr). due to study size, a non-parametric approach was adopted. for principal analysis on primary endpoint, we implemented wilcoxon signed-rank test to compare peepi at inclusion and peepi after initiation of ecco r combined with rr adjustment. regarding secondary endpoints, we performed the same test as for primary endpoint. for endpoints assessed several times, graphs representing variable distributions at each timepoint helped interpreting statistical parameters and tests. in this exploratory twelve patients were recruited during an -month period in centers. table shows characteristics at inclusion. causes of ae were viral pulmonary infections in patients, bacterial pulmonary infection in patients, pneumothoraxes in patients (all with successful pleural drainage at the time of measurement), and exacerbation in a post-surgical context for the last patient. after initiation of ecco r, the rr adjustment algorithm (aiming to improve arterial ph value) resulted in rr decrease in patients, in rr increase in patients, while rr was maintained unchanged in the remaining patients (fig. ) . as a consequence, median minute ventilation was not modified, from ( ; ) to ( ; ) ml/min., p = . . peepi after initiation of ecco r and rr adjustment was not significatively different from basal values: . ( . ; . ) to . ( . ; . ) cmh o, p = . . other respiratory parameters (mechanical ventilator settings, other parameters of hyperinflation, abg values and native lungs vco values) before ecco r initiation and after ecco r initiation combined with rr adjustment are mentioned in table , in additional file : fig. s (gas exchanges parameters) and additional file : fig. s (ventilatory parameters). in the patients with pure respiratory acidosis before ecco r initiation, we found that the rr adjustment in addition to ecco r led to increase in arterial ph from . ( . ; . ) to . ( . ; . ). median extracorporeal blood flow was ( ; ) ml/min., with a median sweep gas flow of ( ; ) l/ min. median extracorporeal vco was ( - ) ml/ min. no variations in hemodynamic parameters were observed without or with ecco r. median ecco r duration was . ( . ; . ) days. median sweep gas flow was l/min. from day to day . additional file : fig. s illustrates the course of total peep and eelv under ecco r until day . of note, an external positive peep (generally between and cmh o) was set after stopping deep sedation beyond the first days of imv, to favor the synchronization between the patient and the mechanical ventilator and to counteract flow limitation. additional file : fig. s illustrates the course of abg parameters and additional file : fig. s illustrates the course of hematological parameters under ecco r until day . mainly, a mild thrombocytopenia was observed in the whole group. inspiratory wob measurements with and without ecco r were possible in only patients during the weaning process, due to premature cessation of ecco r before readiness of patients to perform a low pressure support ventilation trial in patients (mainly in relation with hemorrhagic and thrombotic complications) and due to accidental removal of the nutrivent probe in one patient. wob measurements were performed in conscious patients while breathing at a low pressure support level with ecco r and after switching the sweep gas flow from current value to l/min. for a h period. results are indicated in table . results adding the previously published results of pilot patients using a similar design are presented as additional file : table s . three patients died in-icu and were successfully discharged from icu and hospital. the causes of death were one hemorrhagic stroke during ecco r we report a physiological and clinical evaluation of a low-to-middle extracorporeal blood flow veno-venous ecco r system in very severe ae-copd patients studied shortly after intubation. severity of the patients was assessed by the combination of respiratory acidosis and elevated intrinsic peep under pre-specified respiratory settings aimed to avoid excessive dynamic hyperinflation in deeply sedated imv patients. moreover, all patients were intubated after niv failure. dynamic hyperinflation was also assessed by frc and eelv measurements using the nitrogen washin-washout method, providing original results in this specific copd population. indeed, such patients were not included or were excluded from previous studies [ ] . as expected, we observed very high baseline frc values as compared to published reference values measured in the supine position [ ] . initiation of ecco r was associated with a median extracorporeal co removal amount of ml/min., corresponding to % of the pre-ecco r whole body co production. accordingly, there was a decrease in native lungs' co elimination, which, in conjunction with rr adjustment, permitted to improve arterial ph and to obtain a median absolute decrease in paco of mmhg. this could be beneficial at the early stage of imv in ae copd patients, mainly by minimizing the deleterious effects of acute hypercapnia on ventilator demands, therefore, allowing to shorten deep sedation periods and to rapidly initiate the imv weaning process. we didn't observe any ecco r-induced deleterious effect on oxygenation, as sometimes mentioned in copd patients [ , , ] . however, severely hypoxemic patients were excluded from our study. moreover, we used a low-to-middle blood flow ecco r device, therefore, minimizing the ecco r-induced imbalance between native lung's vo and vco [ ] . we also found a higher sathbo under ecco r, which could at least in part be explained by a left shift of the o dissociation curve due to a decrease in arterial paco and to a parallel increase in arterial ph. although probably too complex for a general clinical use, the algorithm for rr adjustment performed well for arterial ph improvement. such a result was favored by the hemodynamic stability of the patients during ecco r initiation associated with stability in whole body co production. by choice, we didn't retain an algorithm based on v t reduction. this was based on the fact that the absolute value of physiological dead space for co depends of the absolute value of v t , therefore, allowing easier calculations when keeping a fixed absolute v t value [ ] . however, despite the use of quasi-maximal extracorporeal blood and sweep gas flows, the algorithm led to a decrease in rr in only patients. this explains that no improvement in peepi, as the primary outcome measure, was observed in the whole group. the clinical correlate is that the ecco r system was not able in our group of very severe imv copd patients to both improve respiratory acidosis and improve dynamic hyperinflation. however, it's obvious that alternative adjustments algorithms would have been associated with different results. as an example, it could have been possible to first reduce rr and v t after ecco r initiation while keeping paco at the same level. such a strategy very probably would have been associated with a significant decrease in peepi. moreover, in the clinical setting, clinicians will have the possibility to tailor personalized strategies: by simply choosing different paco target and by calculating individual rr adjustment, clinicians have the possibility to arbitrate between respiratory acidosis and dynamic hyperinflation respective improvements. it's also likely that ecco r systems allowing higher extracorporeal co removal amounts could have been associated with higher improvements in hyperinflation parameters and in respiratory acidosis. altogether, this illustrates the need for clinicians to develop clinical strategies of ecco r initiation in deeply sedated imv copd patients. such strategies should be based on the severity of patients, mainly assessed by parameters of dynamic hyperinflation and respiratory acidosis. based on animal and clinical studies, clinicians should also take into account the performances of the different ecco r devices and their effects on native lungs respiratory co elimination [ , ] . providing such strategies could have important implications for the care of patients and for the design of future rcts aiming to prove important clinical benefits of ecco r in very severe ae-copd patients. in addition, we have to mention that our algorithm is not per se suitable for awake patients. this point is important, since ecco r can be proposed in ae-copd patients at high risk of niv failure, or in cases of difficult imv weaning. finally, such low-to-intermediate extracorporeal blood flow devices could be viewed as more suitable for paralyzed moderate ards patients with minimal co production rather than for very severe ae-copd patients. in line with peepi results, frc and v t /t e were not significantly improved in the whole group. one could question the validity of frc measurements in patients treated by ecco r, since ecco r can modify the native lung's respiratory quotient [ ] . however, the nitrogen fraction calculation is based on direct measurements of both o and co fractions when f i o is lower than %, as indicated by the manufacturer [ ] . since our study included only non-severely hypoxemic patients, with fio < %, we are confident in the validity of our results. also, the course of frc results was coherent with peepi results. we previously reported an ecco r-induced benefit in terms of breathing pattern and of work of breathing in imv ae-copd at the end of the weaning process [ ] . using the same design, we observed similar trends in patients. considering a possible lack of statistical power due to the number of patients, we pooled the results of the studies and observed significantly less wob (expressed either in joules per min, per liter of ventilation or per breath) under ecco r. however, since we cannot exclude selection bias, these results are presented with great caution and should not be extrapolated to clinical practice. such results obtained in non-sedated patients only suggest that ecco r could favor a more rapid liberation of imv, as compared to standard care of imv ae-copd patients [ , , ] . moreover, the fact that efficiency of ecco r was observed several days after initiation, could open the way for further studies of different clinical strategies for ecco r weaning. the median duration of ecco r was near to the maximal duration of the circuit as indicated by the manufacturer. such result is important to consider for the choice of ecco r devices and circuits in copd patients. we observed one fatal intracerebral bleeding. such fatality, along with other hemorrhagic complications and thrombosis, illustrate the need to improve the knowledge of the interaction between ecco r circuits, anticoagulation regimen and coagulation system of the patients. indeed, hemorrhagic complications can be favored by an usual mild thrombocytopenia as observed in our study and by other factors such as the occurrence of an acquired willebrand disease, as previously preliminary reported with the hemolung system [ ] and such as a severe endothelial dysfunction, as recently reported by our group [ ] . moreover, fewer side effects could also be expected with higher extracorporeal blood flow devices, as recently shown in ards patients [ ] . nevertheless, the in-hospital mortality rate was found to be lower than the mortality rate observed in imv ae-copd patients by burki et al. with the same device, which could suggest a benefit to initiate ecco r early in the course of imv in copd patients [ ] . one of the main limitations of the study was a too optimistic hypothesis at the time of conception of the study, leading to an overestimation of the ability of hemolung device for co removal in such severe ae-copd patient [ , ] . another limitation was the choice to use standardized mechanical ventilator settings, as part of our usual respiratory bundle in such severe ae-copd patients. it is, therefore, conceivable that more personalized settings could have been more appropriate for certain patients. one other limitation was the assumption of an unchanged v d /v t during all points of the study. indeed, there was a possibility of individual decrease (or increase) in v d /v t in patients with decrease (or increase) in rr. such variations in v d /v t after limited modifications in ventilatory settings have been reported previously in ae-copd patients [ ] . however, there were no differences in the whole group between peepi, plateau pressure, ppeak and eelv values at baseline and after initiation of ecco r combined with rr adjustments. the lack of standard of care control group was also a limit of the study for evaluating dynamic hyperinflation independently of ventilation on a more prolonged time. accordingly, the different initial time points were separated by a delay of h. therefore, we cannot exclude that a more delayed ecco r-induced improvement in regional ventilation could have occurred and allowed decreasing rr, i/e ratio or v t, all important determinants of dynamic hyperinflation. we didn't observed severe hemolysis in contrast to other reports [ , ] . however, the observation is limited by the lack of systematic daily plasma free hemoglobin measurement, which is now a standard practice in our centers. the low inclusion rate of the study and the fact that wob measurements were not possible for the majority of included patients are also clear limitations. using a formalized protocol of rr adjustment, ecco r permitted to effectively improve ph and diminish paco at the early phase of imv in ae-copd patients, but not to diminish dynamic hyperinflation in the whole group. such results could support the clinical implementation of fine-tuned algorithms derived from our protocol taken into account the main goals of ecco r at the early phase of imv, i.e., controlling both hyperinflation and respiratory acidosis. chronic obstructive pulmonary disease randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease outcomes of noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease in the united states extracorporeal carbon dioxide removal for lowering the risk of mechanical ventilation: research questions and clinical potential for the future extracorporeal carbon dioxide removal for acute hypercapnic respiratory failure extracorporeal carbon dioxide removal in patients with chronic obstructive pulmonary disease: a systematic review extracorporeal co removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control the feasibility and safety of extracorporeal carbon dioxide removal to avoid intubation in patients with copd unresponsive to noninvasive ventilation for acute hypercapnic respiratory failure (eclair study): multicentre case-control study control of respiratory drive by extracorporeal co removal in acute exacerbation of copd breathing on non-invasive nava a novel extracorporeal co removal system: results of a pilot study of hypercapnic respiratory failure in patients with pilot study of extracorporeal carbon dioxide removal to facilitate extubation and ambulation in exacerbations of chronic obstructive pulmonary disease venovenous extracorporeal co removal for early extubation in copd exacerbations requiring invasive mechanical ventilation effects of extracorporeal carbon dioxide removal on work of breathing in patients with chronic obstructive pulmonary disease effects of extracorporeal co removal on inspiratory effort and respiratory pattern in patients who fail weaning from mechanical ventilation estimation of functional residual capacity at the bedside using standard monitoring equipment: a modified nitrogen washout/washin technique requiring a small change of the inspired oxygen fraction peep-induced changes in lung volume in acute respiratory distress syndrome two methods to estimate alveolar recruitment lung stress and strain calculations in mechanically ventilated patients in the intensive care unit normal values of functional residual capacity in the sitting and supine positions understanding hypoxemia on ecco r: back to the alveolar gas equation effect of tidal volume on gas exchange and oxygen transport in the adult respiratory distress syndrome veno-venous extracorporeal co removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations utilisation de l'épuration extra-corporelle de dioxyde de carbone dans l'exacerbation de la maladie pulmonaire obstructive chronique: une revue narrative is extracorporeal co removal really "safe" and "less" invasive? observation of blood injury and coagulation impairment during ecco r severity of endothelial dysfunction is associated with the occurrence of hemorrhagic complications in copd patients treated by extracorporeal co removal (ecco r). intensive care med efficacy and safety of lower versus higher co extraction devices to allow ultraprotective ventilation: secondary analysis of the supernova study effects of inspiratory flow waveforms on lung mechanics, gas exchange, and respiratory metabolism in copd patients during mechanical ventilation a -year multicenter, observational, prospective, cohort study on extracorporeal co removal in a large metropolis area publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. supplementary information accompanies this paper at https ://doi. org/ . /s - - -y.additional file : table s . work of breathing (wob) measurements in patients with and without ecco r. figure s . gas exchanges parameters before ecco r initiation and after ecco r initiation and adjustment aiming to improve arterial ph value. figure s . ventilatory parameters before ecco r initiation and after ecco r initiation and adjustment aiming to improve arterial ph value. figure s . daily course of total peep and eelv under ecco r until day . figure s . daily course of abg parameters under ecco r until day . figure s . course of hematological parameters under ecco r until day . the sponsor "direction de la recherche clinique, assistance publique -hôpitaux de paris" was in charge of the general organization of the research. the study was founded by alung (pittsburgh, usa). alung (pittsburgh, usa) and general electric healthcare also provided (non-financial) technical support for the study, mainly by providing ecco r and mechanical ventilator devices and consumables. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. an institutional ethic board (comité de protection des personnes ile-de-france vi, paris, france) approved the protocol (protocole ephebe p -id crb: -a - ). informed consent was obtained from patients' legal representatives. not applicable. dr. diehl reports grants and non-financial support from alung, non-financial support from general electric healthcare, during the conduct of the study; personal fees and non-financial support from xenios novalung (fresenius medical care) outside the submitted work.dr. aissaoui reports non-financial support from astrazeneca, non-financial support from medtronic, non-financial support from abiomed, outside the submitted work.dr. mercat reports personal fees from faron pharmaceuticals, personal fees from air liquide medical systems, grants and personal fees from fisher and paykel, personal fees from medtronic, personal fees from drager, non-financial support from general electric, outside the submitted work. key: cord- -wkwqlnz authors: kobayashi, jun; murata, isamu title: nitric oxide inhalation as an interventional rescue therapy for covid- -induced acute respiratory distress syndrome date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: wkwqlnz covid- is an emerging disease of public health concern. while there is no specific recommended treatment for covid- , nitric oxide has the potential to be of therapeutic value for managing acute respiratory distress syndrome in patients with covid- . however, inhaled nitric oxide has not yet been formally evaluated. given the extent of the covid- pandemic, and the large numbers of hospitalized patients requiring respiratory support, clinical use of inhaled nitric oxide may become an alternate rescue therapy before extracorporeal membrane oxygenation for the management of acute respiratory distress syndrome in patients with covid- . novel coronavirus disease (covid- ) is an emerging disease of public health concern, and the current pandemic is having a major global impact. increasing attention is being focused on the development of therapeutic strategies against this disease. we read, with great interest, the article by li et al. "therapeutic strategies for critically ill patients with covid- " published in this journal [ ] . while there is no specific recommended antiviral treatment, and vaccines have yet to be developed, the authors provided a powerful pharmacological strategy for the treatment of critically ill patients with covid- acute respiratory distress syndrome (ards). in this review article, the drug applications for covid- are well described according to disease severity; however, nitric oxide (no) inhalation therapy, which is not described in this review, may be included in the strategy as a promising therapeutic candidate. in , during the severe acute respiratory syndrome coronavirus (sars-cov) outbreak, a pilot study showed that lowdose inhaled no (max ppm) could shorten the time of ventilatory support for patients infected with sars-cov [ ] . although epidemiological evidence supporting the use of inhaled no in treating covid- has not yet been identified, similar therapeutic effects of no can be expected for patients with covid- due to the genetic similarities between the two viruses [ ] . based on this experience, clinical trials have begun in several medical institutes in the united states, and now a phase clinical trial of inhaled no is being conducted for mechanically ventilated patients with covid- ards to confirm whether no inhalation will become an interventional therapy to rescue patients with this disease [ ] . the inflammatory cytokine storm induced by virus infection is closely related to the development and progression of ards. given the common pathological process leading to virus-induced ards [ ] , previous experience suggests that inhaled no may be useful for managing covid- ards. previously published in vitro studies indicated that no possessed inhibitory effects on sars-cov replication. moreover, growing evidence has shown that inhaled no can reduce inflammatory cell-mediated lung injury by inhibiting neutrophil activation and subsequent pro-inflammatory cytokine release. due to its potent and selective pulmonary vasodilation, inhaled no can lower pulmonary vascular resistance and decrease edema in the alveolar spaces, which enhances ventilation/perfusion matching. in addition, recent evidence also suggests that inhaled no could open access have a wide range of systemic effects via cgmp-dependent and -independent mechanisms leading to a decrease in vascular tone, and a reduced risk of thrombosis and leukocyte adhesion to pulmonary and systemic vascular endothelium [ ] . because no acts as a pro-inflammatory and an anti-inflammatory agent, depending on the amount of no generation and its source, early and timely initiation of inhaled no therapy may prevent cytokine storms following abnormal vascular endothelium/leukocyte interactions. in severe covid- ards with hypoxemia despite optimizing ventilation and other rescue strategies, extracorporeal membrane oxygenation (ecmo) is the final therapeutic option [ ] . however, given the high running cost, limited number of devices, and the skilled medical staff required to perform ecmo, inhaled no, which is relatively of low cost and readily available, may be a promising interventional therapy for patients with severe covid- ards. because inhaled no has been extensively applied to treat pulmonary hypertension, ards, and other respiratory diseases with a relatively good safety profile, we advocate for a clinical trial exploring the use of inhaled no for the management of covid- ards to be conducted as a matter of urgency. therapeutic strategies for critically ill patients with covid- inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in beijing lung pathology of fetal severe acute respiratory syndrome protocol of a randomized controlled trial testing inhaled nitric oxide in mechanically ventilated patients with severe acute respiratory syndrome in covid- (sars-cov- ). medrxiv extrapulmonary effects of inhaled nitric oxide: role of reversible s-nitrosylation of erythrocytic hemoglobin none. dr. jk devised the concept and wrote the manuscript draft, and dr. im helped with editing. both authors read and approved the final manuscript. no funding was used for this report. not applicable.ethics approval and consent to participate not applicable. not applicable. the authors declare that they have no competing interests.received: april accepted: may springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - b v yct authors: darreau, c.; martino, f.; saint-martin, m.; jacquier, s.; hamel, j. f.; nay, m. a.; terzi, n.; ledoux, g.; roche-campo, f.; camous, l.; pene, f.; balzer, t.; bagate, f.; lorber, j.; bouju, p.; marois, c.; robert, r.; gaudry, s.; commereuc, m.; debarre, m.; chudeau, n.; labroca, p.; merouani, k.; egreteau, p. y.; peigne, v.; bornstain, c.; lebas, e.; benezit, f.; vally, s.; lasocki, s.; robert, a.; delbove, a.; lerolle, n. title: use, timing and factors associated with tracheal intubation in septic shock: a prospective multicentric observational study date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: b v yct background: no recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock. patients and methods: this prospective multicenter observational study was conducted in icus in france and spain. all consecutive patients presenting with septic shock were eligible. the use of tracheal intubation was described across the participating icus. a multivariate analysis was performed to identify parameters associated with early intubation (before h following vasopressor onset). results: eight hundred and fifty-nine patients were enrolled. two hundred and nine patients were intubated early ( %, range . – %), across the centers with at least patients included. the cumulative intubation rate during the icu stay was / ( %, range – %). in the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, ph and inability to clear tracheal secretions. global r-square of the model was only % indicating that % of the variability of the intubation process was related to other parameters than those entered in this analysis. conclusion: neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. center effect was important. finally, a vast part of the variability of intubation remained unexplained by patient characteristics. trial registration clinical trials nct , registered on may , . https://clinicaltrials.gov/ct /show/nct ?term=intubatic&draw= &rank= . several international guidelines such as the surviving sepsis campaign help physicians to manage septic shock patient [ ] . however, these guidelines do not indicate the place for tracheal intubation and initiation of mechanical ventilation. several arguments have been put forward in favor of early ventilatory support in septic shock patients, as part of the bundle that should be introduced in the first hours open access *correspondence: nicolas.lerolle@univ-angers.fr medical intensive care unit, angers university hospital, angers, france full list of author information is available at the end of the article of care together with antibiotic, fluid, and vasopressor use. reducing work of breathing and oxygen consumption to maintain adequate tissue oxygenation, preventing diaphragmatic dysfunction and self-inflicted lung injury are expected benefits of invasive ventilation [ , ] . several studies have shown that diaphragmatic dysfunction may occur as early as in the first h of septic shock [ , ] . on the other hand, arguments to challenge a systematic use of ventilatory support in septic shock include immediate complications of tracheal intubation (including hemodynamic impairment) as well as potential side effects related to ventilation (ventilator-induced diaphragm dysfunction, muscle atrophy, ventilation-induced lung injuries, and ventilator-associated pneumonia) [ ] [ ] [ ] . in recent multicenter trials on septic shock patients, the percentage of patients who received invasive ventilation ranged widely from to % [ , ] . in a declarative international survey, % of clinicians declared that the decision to initiate invasive ventilation was based on "common sense" or "human physiological data" [ ] . agreement between responders regarding hemodynamic parameters to initiate mechanical ventilation was low, contrary to neurologic and respiratory criteria. in acute neurologic and respiratory failures, indications for intubation and mechanical ventilation are generally well-accepted across studies, based on reliable quantitative parameters (respiratory rate, use of accessory respiratory muscles, pao / fio ratio, and glasgow coma score) [ ] [ ] [ ] [ ] [ ] . how physicians apply these criteria in septic shock patients and whether other parameters, in particular hemodynamic, are involved is unknown. to assess use, timing and factors associated with tracheal intubation in septic shock patients, we conducted a multicenter observational prospective study in intensive care units (icus) in france and spain. our hypothesis was that in the absence of specific recommendations in the sepsis care bundle, use and timing of tracheal intubation might vary greatly between patients. the intubatic study was a prospective, multicenter observational study conducted in icus ( in france and one in spain) in both academic and non-academic hospitals. the primary endpoint was to assess rate of intubation, early and late, and factors associated with intubation practice in septic shock patients. the secondary endpoint was to assess mortality according to intubation. we considered a time window of h following vasopressor onset to define early intubation, from the results of our previous study [ ] . two approaches were used to assess the parameters associated with early intubation. first, criteria for standard indications for early tracheal intubation were defined a priori, based on accepted recommendations for invasive ventilation initiation in neurologic or respiratory failure. frequency of early intubation and patient characteristics were described among those with such criteria [ ] [ ] [ ] [ ] [ ] . second, a multivariate analysis entering a wide array of parameters was performed to assess the link between these parameters and early intubation among all patients. an evaluation of the goodness-of-fit of the model was performed to determine the amount of early intubation variability explained by the different covariates. the inclusion period ran from may to october . icus were involved gradually and had -months to include patients. the protocol allowed for a maximum of patients enrolled per center. physicians participating in the study were aware of its main objective, but were instructed to perform patient's care as they usually did, and no specific hypothesis was put forward regarding optimal management of these patients. patients, or a proxy if the patient was deemed unable to consent, received oral and written information about the study, and oral consent was obtained before inclusion. when a proxy gave the initial consent, the patient's consent was further obtained whenever possible. this study was approved by the angers university hospital ethics committee (n° / ). patients aged years and above were eligible if admitted in a participating icu for septic shock, defined by a documented or clinical suspicion of infection and hypotension requiring vasopressor infusion despite adequate fluid loading. patients could be included if a vasopressor was introduced in the h preceding icu admission, i.e., in another hospital or the emergency room. patients were not eligible if vasopressor infusion was started after tracheal intubation and mechanical ventilation (noninvasive ventilation through facial mask did not prevent inclusion). incapacitated adults, pregnant women, patients with a decision of withdrawal or withholding of care before icu admission, patients without social health insurance and patients who refused to participate in the study were not included. age, sex, and main comorbidities were noted. saps ii and sofa score were calculated h after icu admission [ , ] . infection site, causal pathogen(s), and nosocomial or community-acquired subset of infection were registered. hemodynamic, respiratory, and neurological parameters were recorded between the time of vasopressor onset (h ) and h : oxygen administration device and pao /fio ratio (see additional file : table s for fio determination), respiratory rate, accessory inspiratory muscle use, paradoxical abdominal breathing, inability to cough or to clear tracheal secretions, vasopressor infusion rate (norepinephrine or epinephrine in all centers), arterial lactate concentration, serum creatinine level, urine output, and glasgow coma score. in patients not intubated by h , the worst values of acute neurological and respiratory severity parameters over this period were registered. in patients intubated before h , the worst parameters between h and intubation were registered. fluid loading from the first hypotension to h was noted. durations of icu stay, hospital stay, vasopressor infusion, mechanical ventilation, and renal replacement therapy were registered. icu, hospital and -day mortality were recorded. criteria qualifying for theoretical immediate tracheal intubation during the h -h time window were either (independently of intubation being performed or not): • neurological failure: glasgow coma scale < . • respiratory failure, two criteria among these had to be present: oxygen saturation less than % during more than min despite optimized oxygen administration, respiratory rate more than per minute, significant accessory respiratory muscle use, respiratory acidosis defined by ph < . and pco > mmhg, hypoxemia with pao /fio ratio inferior to , and inability to cough or clear tracheal secretions. these criteria are generally associated with strong recommendations for immediate tracheal intubation in case of neurological or respiratory failure [ ] [ ] [ ] [ ] [ ] . we sought to include more than patients, estimating an early intubation rate ranging from to %. this allowed for the selection of to covariates to be included in a multivariable model for explaining early intubation [ ] . continuous data were summarized as the mean and standard deviation or median with inter-quartile range as required and compared using the kruskal-wallis test. categorical data were expressed as number and percentage and compared using the fisher exact test. the cumulative hazard function of event occurrence was estimated using the nelson-aalen procedure. early intubation was studied through a mixed-effects logistic regression model, considering a list of covariates (considered as fixed effect covariates). covariates entered in the multivariate analysis were chosen a priori based on their relevance after reaching a consensus between nl, jfh, ad, msm, fm, sj and cd based on published literature review and advice from experts of the topics (prof. pierre asfar and prof. laurent brochard). the practice variation between participating centers was also considered in this model by including "center" as a random effect covariate. patients intubated for emergent surgery procedure were excluded for this analysis. no imputation was performed for missing data. the goodness-of-fit was assessed using a mckelvey pseudo r-squared measure, evaluating the outcome variability based on the constructed model [ ] . the weight of each covariate included in the outcome variability explanation was assessed through the percentage of mckelvey pseudo r-squared associated with this covariate [ ] . graphical representation of patients survival was performed with kaplan-meier method, and survival rates were compared with log-rank test. all the tests were twosided considering a type i error set at . . the statistical analyses were performed using stata ® . . eight hundred and fifty-nine patients were enrolled in the study. early intubation (i.e., in the h following vasopressor initiation) was performed in patients ( %). at h, additional patients had been intubated and were intubated between h and h , and only one thereafter during the icu stay. cumulative intubation rate over the icu stay was therefore / ( %, range among the centers with at least patients included - %; q -q - %). the hazard of being intubated over the first h is displayed in fig. . the percentage of patients intubated early ranged from . to %, [q -q : . - . %] across the centers with at least patients included (these centers included patients), see fig. . data of patients intubated early, late (after h ) and never intubated are displayed in table : parameters associated with acute severity (i.e., respiratory and hemodynamic variables), chemotherapy, presence of fungus and some site of infections (digestive and urinary) were significantly different between patients intubated early, late, and never intubated. two hundred and twenty-six patients reached neurological or respiratory standard criteria for theoretical immediate intubation by h and patients did not reach such criteria by h . figure shows frequency of intubation at h and h in these two subgroups of patients, showing that among patients with neurological or respiratory standard criteria for theoretical immediate intubation by h , only % were intubated at this time ( % by h ). one hundred and fourteen patients could not be classified due to missing data. in the group of patients with standard criteria for theoretical immediate intubation, patients intubated early had more severe respiratory, hemodynamic and neurologic parameters in comparison with patients not intubated before h and had a worse outcome when considering the number of days without organ support and survival (see additional file : table s ). predictor variables used in the mixed-effects logistic regression model are detailed in table and its footnote. according to physicians, ( . %) patients were intubated for emergent surgical procedures; these patients were excluded from the dataset for the analysis. seven parameters were significantly associated with intubation by h and ranked in the model as follows by decreasing weight: glasgow score, center effect, use of accessory respiratory muscles, lactate, vasopressor dose, ph and inability to clear tracheal secretions. however, the global r-square of the model was only % indicating that % of the variance of the decision to intubate or not was related to other variables than those entered in this analysis. finally, mortality and other outcomes were significantly different between patients intubated early, late, and never intubated (see table ). survival according to intubation status is displayed in fig. . patients never intubated had the higher survival and better outcomes. comparison of patients intubated early vs. late showed no survival data are n (%) or mean ± sd a worst value recorded between h and h , or between h and immediately before intubation if intubation performed before h b at h fig. intubation frequency at h and h in patients with and without neurological or respiratory standard criteria for theoretical immediate intubation by h difference, but longer length of icu and hospital stay in these latter patients. in this observational study conducted over patients in icus, early intubation (in the h following vasopressor onset) was performed in % of the patients. thirty-eight percent were intubated at h . a wide variation was observed across centers. in the patients with standard criteria usually recognized for immediate tracheal intubation due to neurological and/or respiratory failure before h , only half of them were intubated early [ ] [ ] [ ] [ ] [ ] . in a multivariate analysis entering a wide array of parameters, seven neurological, respiratory and hemodynamics acute severity parameters were associated with early intubation. center effect was also prominent. finally, the model only explained % of the variance of early intubation, meaning that % was related to unmeasured parameters. the survival curves showed no mortality difference between early and delayed intubation. conversely, never-intubated patients had better survival. few studies have specifically evaluated tracheal intubation in septic shock patients. from large interventional studies on septic shock, although not designed to study intubation specifically, a trend towards lesser intubation rates can be observed, from % in the - period to % in recent years, which is in line with the rates observed in our study [ , , ] . in a monocentric qualitative survey, bauer et al. analyzed the factors that influenced the decision of early intubation in sepsis-associated respiratory failure. they showed that the decision to intubate was not solely based on clinical parameters, but also on clinician factors like background, experience or instinct and system factors like organizational structure or workload [ ] . our study confirms and extends these data by showing quantitatively that a vast component of the decision process to intubate in septic shock patients is not related to acute severity parameters or baseline conditions. initiating tracheal intubation and mechanical ventilation in a septic shock patient is not an inconsequential decision with potential harms and benefit as pointed out in the introduction. to this date, it is impossible to determine whether the place given to tracheal intubation in septic shock patients is adequate or not. the model used in this study only displays the parameters probably taken into account in the decision process, but not if these parameters are appropriate or not for the patient's outcome. although we did not observe any difference in mortality between patients intubated early and late, we cannot conclude on the adequate timing for this procedure. indeed, the fact that our model only explains half of the variance leaves a wide range of parameters beyond the scope of our analysis. those unknown and possibly important parameters make the impact of intubation and its timing on outcome difficult to analyze in a multivariable model or a propensity score model. our study has several limitations. the -h threshold for defining early intubation could be discussed. as already cited, a previous study showed that tracheal intubation was mostly performed during the first h of septic shock [ ] . six hours is an accepted time frame for early intervention in sepsis [ ] . to take into account the workload requirements and organizational factors of this demanding procedure, we extended to the first h the time frame for defining early tracheal intubation. missing data were observed in % of included patients, which may impact the accuracy of our results. we may have missed some important parameters that should have been considered to explain the decision to intubate. however, the prospective and dedicated design of our study allowed the monitoring of a wide range of baseline and clinical parameters. we may also have missed the adequate time frame during which parameters should have been monitored. in a future study, organizational factors (physician experience, workload, etc.) may be registered. another hypothesis is that this uncertainty represents clinical equipoise, opening the way for a randomized trial comparing early ( h) vs. late (rescue) tracheal intubation. in conclusion, we observed that % of patients with septic shock were intubated by h and % at h . in a multivariate analysis, neurological, respiratory and hemodynamic parameters were associated with early intubation. center effect had a strong influence on the medical and surgical intensive care unit, alençon hospital, alençon, france. medical and surgical intensive care unit, morlaix hospital, morlaix, france. medical and surgical intensive care unit, métropole savoie hospital, chambéry, france. medical intensive care unit surviving sepsis campaign guidelines for management of severe sepsis and septic shock mechanical ventilation protects against diaphragm injury in sepsis: interaction of oxidative and mechanical stresses distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs mechanical ventilation to minimize progression of lung injury in acute respiratory failure diaphragmatic fatigue during sepsis and septic shock respiratory muscle fatigue: a cause of ventilatory failure in septic shock incidence of and risk factors for severe cardiovascular collapse after endotracheal intubation in the icu: a multicenter observational study rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans the epidemiology of septic shock in french intensive care units: the prospective multicenter cohort episs study goal-directed therapy for septic shock-a patient-level meta-analysis criteria for initiation of invasive ventilation in septic shock: an international survey predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial predictors of intubation in patients with acute hypoxemic respiratory failure treated with a noninvasive oxygenation strategy high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure impact of endotracheal intubation on septic shock outcome: a post hoc analysis of the sepsis-pam trial a new simplified acute physiology score (saps ii) based on a european/north american multicenter study the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine a simulation study of the number of events per variable in logistic regression analysis a statistical model for the analysis of ordinal level dependent variables partial credit model: estimations and tests of fit with pcmodel high versus low blood-pressure target in patients with septic shock current epidemiology of septic shock: the cub-réa network timing of intubation in acute respiratory failure associated with sepsis: a mixed methods study early goal-directed therapy in the treatment of severe sepsis and septic shock publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we thank prof. pierre asfar and prof. laurent brochard for insightful comment on the manuscript and on the covariates to select. model and, an important part of the variance remained unexplained. a significant part of the decision to intubate seemed independent of patient characteristics. supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : table s . conversion table for fio determination. table s . comparison between patients intubated early and not intubated early in the group of patients with standard criteria for early endotracheal intubation.abbreviations icu: intensive care unit; pao : arterial oxygen partial pressure; fio : inspired oxygen fraction; saps ii: simplified acute physiologic parameter; sofa: sequential organ failure assessment; vo : oxygen consumption; nyha: new york heart association functional classification; paco : arterial carbon dioxide partial pressure; spo : oxygen pulsed saturation.authors' contributions cd, fm, msm, sj, ad and nl contributed equally to the redaction of the protocol, investigation, enrollment, data collection and manuscript redaction. jfh contributed in data management and statistical analysis. all other authors contributed to enrollment and data collection. all authors read and approved the final manuscript. the present study has been conducted without any financial support. the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. this study was approved by the angers university hospital ethics committee (n° / ). not applicable. the authors declare that they have no competing interests. key: cord- -iryb v z authors: kao, kuo-chin; chang, ko-wei; chan, ming-cheng; liang, shinn-jye; chien, ying-chun; hu, han-chung; chiu, li-chung; chen, wei-chih; fang, wen-feng; chen, yu-mu; sheu, chau-chyun; tsai, ming-ju; perng, wann-cherng; peng, chung-kan; wu, chieh-liang; wang, hao-chien; yang, kuang-yao title: predictors of survival in patients with influenza pneumonia-related severe acute respiratory distress syndrome treated with prone positioning date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: iryb v z background: patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ards). prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ards. the aim of this study is to investigate the survival predictors of prone positioning in patients with ards caused by influenza pneumonia. methods: this retrospective study was conducted by eight tertiary referral centers in taiwan. from january to march in , all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ards and receiving prone positioning were enrolled. demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis. results: during the study period, patients with severe influenza pneumonia were screened and patients met the diagnosis of ards. totally, patients receiving prone positioning were included for analysis. the -day survivors had lower acute physiology and chronic health evaluation (apache) ii score, pneumonia severity index (psi), creatinine level and lower rate of receiving renal replacement therapy than non-survivors ( . ± . vs. . ± . , p = . ; . ± . vs. . ± . , p = . ; . ± . mg/dl vs. . ± . mg/dl, p = . ; and % vs. %, p < . ). multivariate cox regression analysis identified psi (hazard ratio . , % confidence interval . – . ; p < . ), renal replacement therapy (hazard ratio . , % confidence interval . – . ; p < . ), and increase in dynamic driving pressure (hazard ratio . , % confidence interval . – . ; p = . ) which were independent predictors associated with -day mortality. conclusions: in the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ards, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with -day mortality in patients with influenza pneumonia-related ards receiving prone positioning. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. severe complicated influenza including pneumonia, myocarditis and neurologic complications are still a burden on intensive care units (icu) nowadays, especially viral or secondary bacteria pneumonia-induced acute respiratory distress syndrome (ards) [ , ] . during the winter season in , there was an outbreak of influenza in taiwan. totally, subjects were admitted to icus due to severe complicated influenza pneumonia according to the data from the centers for disease control of taiwan [ ] . patients with influenza pneumonia needing mechanical ventilation were at high risk of rapid progression to ards. for the pandemic h n virus infection, - % of patients admitted to icus had complications with ards [ , ] . there are several therapeutic options for refractory hypoxemia in patients with severe ards [ , ] , but only a few options have been confirmed with clinical validity by previous studies, including higher positive endexpiratory pressure (peep) [ , ] , lower tidal volume [ ] , neuromuscular blocking agents [ ] and prone positioning [ ] . prone positioning was first suggested in [ ] ; however, the clinical benefit of prone positioning in patients with ards was not confirmed until when the proseva study showed decreased -day and -day mortality and increased ventilator-free days only when it was started early and there were sufficiently long sessions [ ] . further, meta-analysis by cochrane database also revealed that prone positioning would reduce the mortality rate when used with lung-protective strategies and longer duration in patients with severe ards [ , ] . few studies have explored the effect of prone positioning focused on influenza pneumonia-related ards patients. xu et al. [ ] studied h n influenza patients with prone positioning, and decrease in carbon dioxide retention was noted, but no clinical outcome was mentioned. moreover, what factors that can predict the efficacy of prone positioning in severe ards are not entirely clear [ ] . the aim of this study is to investigate the survival predictors of prone positioning in patients with severe ards caused by influenza pneumonia. this multicenter retrospective cohort study was conducted by the taiwan severe influenza research consortium (tsirc), which included eight tertiary referral centers (four hospitals in northern taiwan, two hospitals in central taiwan and two hospitals in southern taiwan). over a period of months from january to march in , all patients with the virology-proven influenza infection who were admitted to icus due to severe complicated influenza in these eight hospitals were collected and their data were analyzed. all patients diagnosed as severe ards according to berlin definition and also receiving prone positioning were collected for investigation [ ] . the berlin definition of ards was defined by acute onset within week, bilateral lungs opacities, no evidence of cardiac failure-related hydrostatic edema by echocardiography, and pao /fio ratio < mm hg with positive end-expiratory pressure (peep) ≥ cm h o. the demographic and laboratory data, treatment record, mechanical ventilation settings, and clinical outcomes were analyzed from the electronic medical records with a standardized case report form in each hospital. university hospital rind, tri-service general hospital - - - ). the need for informed consent was waived, and patients' data were anonymized and de-identified prior to analysis. influenza infection was confirmed by one of the following tests revealing as positive including the rapid antigen test, nucleic acid reverse transcriptase polymerase chain reaction (rt-pcr), viral culture sampling from nasopharynx swab, throat swab, sputum or bronchoalveolar lavage and positive serum antibody serologic test (antibody titers increased more than times from acute to convalescent stages). the usual practice in the units was that patients be ventilated with lung-protective strategy by low tidal volume - ml/kg of predict body weight plus low positive endexpiratory pressure (peep)-oxygen fraction in air (fio ) table for pressure-controlled or volume-controlled ventilation [ ] . ventilation was monitored by arterial blood gas measurements, with ventilator settings changed as needed. pulse oximetry (spo ) was used to monitor oxygenation, and ventilatory settings were adjusted to maintain spo > % or pao > mm hg and to avoid raising the plateau pressure > cm h o. the method of prone positioning complied with the proseva study [ ] . doses of neuromuscular blocking agent with intravenous cisatracurium and sedatives with intravenous midazolam were adjusted to maintain synchrony between the ventilator and the patient's breathing, as well as hemodynamics. the criteria for stopping prone positioning were any of the following: improvement in oxygenation (defined as a pao /fio ratio ≥ mm hg, with a peep of ≤ cm h o and an fio ≤ . ), a decrease in the pao /fio ratio ≥ % or complications happening during prone positioning such as spo ≤ % or pao /fio ratio ≤ mm hg, severe cardiac arrhythmia, systolic blood pressure ≤ mm hg and any other life-threatening condition for which the intensivist decided to stop the prone positioning. the laboratory data including baseline characteristics, underlying disease, complete blood count, differential count and biochemistry data were obtained when the patient was admitted to the icu. the mechanical ventilator settings were recorded such as peak inspiratory pressure, peep, artery blood gas, partial pressure of oxygen in arterial blood (pao ), pao /fio ratio, tidal volume, dynamic driving pressure and dynamic compliance of the respiratory system before and day after the first prone positioning. the above physiological data were recorded before prone positioning on the supine position and day after first prone positioning on the prone position. the dynamic driving pressure and dynamic compliance were computed as peak pressure minus peep and tidal volume divided by peak pressure minus peep. the severity scores including pneumonia severity index (psi) [ ] , acute physiology and chronic health evaluation ii (apache ii) score [ ] , curb- (confusion, urea > mmol/l, respiratory rate ≥ /min, blood pressure [systolic < mm hg or diastolic ≤ mm hg] and age ≥ years) pneumonia severity score [ ] and sequential organ failure assessment (sofa) score [ ] were collected on the icu admission day. statistical analyses and database management were performed using spss version . . (spss inc., chicago, il). the data were presented as number (percentages) for nominal variables, and as mean ± standard deviation for continuous variables. the chi square test was used to compare the nominal variables, and the student's t test was used to compare the continuous variables. cox proportional hazard models were used with covariates significantly different between survivors and non-survivors at the threshold of . and mortality at day as the dependent variable. calibration was assessed using hosmer-lemeshow goodness-of-fit test (c statistic, goodness of fit was defined as a p value > . ), and discrimination was assessed by the area under the receiver operating curves. even though peak airway pressure, dynamic driving pressure, and compliance are mathematically coupled, we planned to formally test the collinearity within them and, if verified, to use a specific cox model for each. we also included those collinear variables two-by-two into three additional cox regression models [ ] , besides the other covariates. one model pertained to peak airway pressure and dynamic driving pressure, one to peak airway pressure and compliance, and one to dynamic driving pressure and compliance. if both variables in the couple lacked significance, the conclusion could be that the same information was carried by each component of the couple. if one of the variables in the couple remained significantly correlated with survival, this variable would be more informative than the other in the couple. univariate and multivariate cox proportional hazard regression models were used to estimate the hazard ratio (hr). in this study, we used the two-tailed test, and the definition of significance was p value < . . in total, patients with virology-proven severe influenza pneumonia were admitted to icus and screened during the study period. there were patients with influenza a (including h n in patients and h n in patients), patients with influenza b, and patients with undetermined influenza type. of these patients, patients ( %) met the diagnosis of severe influenza pneumonia-related ards. the rates of mild, moderate and severe ards were % ( / ), % ( / ) and % ( / ), respectively. of these patients with ards, patients ( %) receiving prone positioning were included for analysis (fig. ) . the rate of receiving prone positioning was % ( / ) in mild, % ( / ) in moderate and % ( / ) in severe ards, respectively (p = . ). the characteristics of the subjects according to the -day survivors and non-survivors are summarized in table . the mean age was . ± . years, and patients ( %) were male. the duration of prone positioning of survivors and non-survivors was not significantly different ( . ± . days vs. . ± . days, p = . ). the survivors had lower apache ii score, psi, creatinine level and lower rate of receiving renal replacement therapy than did non-survivors ( . ± . vs. . ± . , p = . ; . ± . vs. . ± . , p = . ; . ± . mg/dl vs. . ± . mg/dl, p = . ; and % vs. %, p < . ). regarding the oxygenation, the mean pao /fio ratio of these patients before prone positioning was . ± . mm hg. before prone positioning, there were no significant differences in the pao /fio ratio, paco , tidal volume, peep, peak airway pressure, dynamic driving pressure and dynamic compliance between surviving and non-surviving patients. the data regarding the gas exchange and lung mechanics were recorded before prone positioning and after -day prone positioning (table ) . for the -day survivors, there were no significant differences in these parameters compared with -day non-survivors except for peak airway pressure. after prone positioning, the -day survivors had decreased peak airway pressure (− . ± . cm h o) and the -day non-survivors had increased peak airway pressure ( . ± . cm h o). compared with -day non-survivors, the peak airway pressure and dynamic driving pressure were both decreased in -day survivors (− . ± . univariate analysis was used to identify variables that have prognostic value for -day mortality, and multivariate cox regression analysis was used to identify variables that did have significant predictive value (table ) . pneumonia severity index (hazard ratio . , % confidence interval . - . ; p < . ), renal replacement therapy (hazard ratio . , % confidence interval . - . ; p < . ) and increased dynamic driving pressure (hazard ratio . , % confidence interval . - . ; p = . ) were identified as significant and independent predictors associated with -day mortality. as the collinearity between Δ dynamic driving pressure, Δ peak airway pressure and Δ dynamic compliance was statistically significant, a cox model was constructed for each of these variables. after multiple adjustments of coupled variables, three additional cox models were performed (additional file ). when Δ dynamic driving pressure and Δ peak airway pressure were analyzed two-by-two, Δ dynamic driving pressure remained significant but Δ peak airway pressure did not (model in additional file ). when Δ dynamic driving pressure and Δ dynamic compliance were analyzed two-by-two, Δ dynamic driving pressure remained significant but Δ dynamic compliance did not (model in additional file ). when Δ peak airway pressure and Δ dynamic compliance were analyzed two-by-two, both did not reveal significant (model in additional file ). receiver operating curves analysis and c statistic of variables of predictors revealed . in psi ( % confidence interval, . - . , p = . ), . in renal replacement therapy ( % confidence interval, . - . , p = . ) and . ( % confidence interval, . - . , p = . ) in delta dynamic driving pressure (fig. ). the aim of this multicenter retrospective study was to evaluate the effect of prone positioning focusing on patients with influenza pneumonia-related ards. after multivariate cox regression analysis, psi, renal replacement therapy and increased dynamic driving pressure were associated with -day mortality in patients with influenza pneumonia-related ards receiving prone positioning. most of the studies evaluating the effect of prone positioning were in ards patients with heterogeneous risk factors [ , ] . for specific conditions such as burns, prone positioning has been demonstrated to safely implement and improve oxygenation (in burn patients with severe ards) in a burn intensive care unit [ ] . the present study was more homogenous and specific to patients with ards caused by influenza pneumonia. systematic review and meta-analysis studies in prone positioning have revealed decreased mortality in patients with severe acute hypoxemic respiratory failure, but not in less severe hypoxemia. survival benefits were noted using a range of pao /fio ratio thresholds up to approximately mm hg [ ] or less than mm hg [ ] . in the present study, the pao /fio ratio was . ± . mm hg before prone positioning. however, the pao /fio ratio was not significantly different between -day survivors and -day non-survivors ( . ± . mm hg vs. . ± . mm hg, p = . ). in terms of the response of prone positioning to ards, the different entities of the risk factor possibly produce different outcomes. in addition to severity of hypoxemia, further clinical trials would assist in clarifying the survival benefits of prone positioning in the specific risk factors. some studies have shown that acute kidney injury (aki) was common and an independent risk factor for mortality in patients with influenza a [ ] [ ] [ ] [ ] . in patients with severe ards caused by h n influenza pneumonia, a recent study also revealed aki was common and demonstrated significantly increased mortality [ ] . the % mortality rate among the patients requiring renal replacement therapy was significantly higher than the % mortality rate among the patients not requiring renal replacement therapy. the present study in patients receiving prone positioning caused by influenza pneumonia-related ards demonstrated that the requirement for renal replacement therapy had nearly times the mortality rate (hazard ratio . ) than patients not requiring renal replacement therapy. in order to reduce the mortality in patients with severe ards caused by h n influenza pneumonia, it is important to prevent development ards acute respiratory distress syndrome, bmi body mass index, apache ii acute physical and chronic health evaluation, sofa sequential organ function assessment, psi pneumonia severity index, curb- curb- for pneumonia severity, wbc white blood cell count, paco atrial pressure of carbon dioxide in arterial blood, pao atrial pressure of oxygen in arterial blood, fio oxygen fraction in air, pbw predict body weight, peep positive end-expiratory pressure all values are expressed as the number of patients (percentage) or mean ± sd *p < . : survivors versus non-survivors of aki and need for renal replacement therapy by avoiding nephrotoxic agents and supplying sufficient renal perfusion and oxygenation. amato and colleagues analyzed randomized controlled trials in ards patients and demonstrated that driving pressure was the strongest predictor of mortality [ ] . a secondary analysis of data from ards patients enrolled in two independent randomized controlled trials revealed that when ventilating patients with low tidal volume, driving pressure was a risk factor for death in ards patients, as was plateau pressure or compliance of respiratory system [ ] . airway driving pressure was significantly related to lung stress and could detect lung over-stress with acceptable accuracy (r = . p < . and r = . p < . at and cm h o of peep) in ards patients [ ] . furthermore, the apronet study on prone positioning of ards patients found that prone positioning was associated with low complication rates, significant increase in oxygenation, and a significant decrease in driving pressure [ ( - cm h o) to [ ] [ ] [ ] [ ] [ ] [ ] [ ] cm h o, p = . ] [ ] . our previous study for severe ards patients with ecmo revealed that higher dynamic driving pressure [hazard ratio . ( . - . ), p = . ] during the first days of ecmo was one of the factors independently associated with icu mortality [ ] . the present study in influenza pneumonia-related ards patients receiving prone positioning also found that increased dynamic driving pressure (hazard ratio . , % confidence interval . - . ; p = . ) was identified as ards acute respiratory distress syndrome, Δ change between before and after prone positioning day, pao partial pressure of oxygen in arterial blood, paco atrial pressure of carbon dioxide in arterial blood, one of the independent predictors associated with -day mortality. it was suggested that ventilatory support with lung-protective strategy with low tidal volume and optimal peep level be applied, and these be then adjusted according to the driving pressure, ideally less than cm h o, although this limit should be addressed in future studies [ ] . despite some studies associating driving pressure with physiological and clinical outcomes, it is necessary to evaluate the driving pressure as a primary end point during ventilatory setting in ards patients in the near future. the lung safe study showed that the use of prone positioning actually depended on the severity of hypoxemia, from % in mild to . % in moderate and to . % in severe ards [ ] . a prospective international prevalence study (the apronet study, ards prone position network) found that the rates of prone positioning were up to . %, . % and . % in mild, moderate and severe ards [ ] . in our study, the rates of prone positioning were %, % and % in mild, moderate and severe ards, respectively. the substantially different rates in the use of the prone positioning may reflect the management bias of prone positioning in patients with ards between the different studies. furthermore, among our eight involved hospitals, the rate of prone positioning varied from % ( / ) to % ( / ) and the bias even existed between different hospitals in the same study. it is important to be homogenous on the indication and management in the selected prone position as one of the standard interventions in severe ards. this study has some limitations. firstly, since this study is retrospective, some patients or data might be missing. secondly, the primary end point of this study was -day mortality, and the value of computed power was . . this was a retrospective study, and patients with severe ards receiving prone positioning were analyzed. although more patients were needed to increase the power of this study, the limitation was from the nature of retrospective study within a -month period. thirdly, prone positioning is not a routine intervention in the management of ards and has no standard procedure such as how many hours a day, how to perform it or how to protect the patients. in this study, even though every patient had prone positioning for more than h a day, the exact duration showed little difference between each hospital. fourthly, the change in physiological measurements pertains to a difference between supine and prone position, and hence, the impact of chest wall is not taken into account. finally, in this study, we focused on influenza-related ards patients, and whether the result can be extrapolated to all patients with ards is unknown, requiring further investigation. to confirm the benefit of prone positioning in ards especially in influenza this study was designed to evaluate the effect of prone positioning in influenza pneumonia-related ards patients. after multivariate cox regression analysis, it was found that psi, renal replacement therapy and increased dynamic driving pressure were associated with -day mortality in patients with influenza pneumoniarelated ards receiving prone positioning. h n : viral pneumonia as a cause of acute respiratory distress syndrome pathogenesis of influenzainduced acute respiratory distress syndrome taiwan national infectious disease statistics system. taiwan centers for disease control critical care services and h n influenza in australia and new zealand critically ill patients with influenza a(h n ) infection in canada the berlin definition of ards: an expanded rationale, justification, and supplementary material european society of intensive care medicine, and society of critical care medicine an official american thoracic society/european society of intensive care medicine/society of critical care medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome neuromuscular blockers in early acute respiratory distress syndrome prone positioning in severe acute respiratory distress syndrome conference on the scientific basis of respiratory therapy. pulmonary physiotherapy in the pediatric age group. comments of a devil's advocate prone position for acute respiratory failure in adults effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis a multicenter retrospective review of prone position ventilation (ppv) in treatment of severe human h n avian flu treatment of ards with prone positioning acute respiratory distress syndrome: the berlin definition a prediction rule to identify lowrisk patients with community-acquired pneumonia apache ii: a severity of disease classification system defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine effect of driving pressure on mortality in ards patients during lung protective mechanical ventilation in two randomized controlled trials prone positioning improves oxygenation in adult burn patients with severe acute respiratory distress syndrome prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis prone position for acute respiratory distress syndrome: a systematic review and meta-analysis writing committee of the who consultation on clinical aspects of pandemic (h n ) influenza influenza a infection and acute kidney injury: incidence, risk factors, and complications acute kidney injury among critically ill patients with pandemic h n influenza a in canada: cohort study acute kidney injury in criticallyill adult patients with seasonal influenza infection outcomes of acute kidney injury in patients with severe ards due to influenza a(h n ) pdm virus driving pressure and survival in the acute respiratory distress syndrome airway driving pressure and lung stress in ards patients a prospective international observational prevalence study on prone positioning of ards patients: the apronet (ards prone position network) study dynamic driving pressure associated with mortality in acute respiratory distress syndrome with extracorporeal membrane oxygenation driving pressure: a marker of severity, a safety limit, or a goal for mechanical ventilation? epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in countries we thank professor meng-chih lin, the president of the taiwan society of pulmonary and critical care medicine, who organized and coached the tsirc team. on behalf of all authors, the corresponding author states that there is no conflict of interest. not applicable. not applicable. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - gutb m authors: lapidus, nathanael; zhou, xianlong; carrat, fabrice; riou, bruno; zhao, yan; hejblum, gilles title: biased and unbiased estimation of the average length of stay in intensive care units in the covid- pandemic date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: gutb m background: the average length of stay (los) in the intensive care unit (icu_alos) is a helpful parameter summarizing critical bed occupancy. during the outbreak of a novel virus, estimating early a reliable icu_alos estimate of infected patients is critical to accurately parameterize models examining mitigation and preparedness scenarios. methods: two estimation methods of icu_alos were compared: the average los of already discharged patients at the date of estimation (dpe), and a standard parametric method used for analyzing time-to-event data which fits a given distribution to observed data and includes the censored stays of patients still treated in the icu at the date of estimation (cpe). methods were compared on a series of all covid- consecutive cases (n = ) admitted in an icu devoted to such patients. at the last follow-up date, days after the first admission, all patients but one had been discharged. a simulation study investigated the generalizability of the methods' patterns. cpe and dpe estimates were also compared to covid- estimates reported to date. results: los ≥ days concerned out of the patients ( %), including of the deaths observed. two months after the first admission, ( %) patients had been discharged, with corresponding dpe and cpe estimates of icu_alos ( % ci) at . days ( . – . ) and . days ( . – . ), respectively. series' true icu_alos was greater than days, well above reported estimates to date. conclusions: discharges of short stays are more likely observed earlier during the course of an outbreak. cautious unbiased icu_alos estimates suggest parameterizing a higher burden of icu bed occupancy than that adopted to date in covid- forecasting models. funding: support by the national natural science foundation of china ( to dr. zhou) and the emergency response project of hubei science and technology department ( fca to pr. zhao). the spread of a novel coronavirus (sars-cov- ) has brought about a pandemic referred to as the covid- pandemic [ ] . this pandemic has resulted in a worldwide crisis with unprecedented decisions of restrictive non-pharmacological mitigation interventions taken at local, regional, or national levels. a major aim of these measures is lessening as much as possible the daily number of new individuals requiring an admission in intensive care units (icu) in order to be able to appropriately manage them in the healthcare system and sustain an appropriate management for the rest of the population [ ] . a fast inflow of new admissions in the icu has critical consequences within a short time. for example, between march and april in france, the number of icu beds occupied by covid- infected persons dramatically increased from to [ ] , corresponding to an average daily increase of % additional beds. such a situation requires a massive and rapid increase of icu facilities and the french minister of health announced on march that the nationwide capacity had been increased from to , critical beds [ ] . the underlying mathematics are simple: an average unbalanced increase of % during days implies that at day , the resulting occupancy would be that of day multiplied by a factor . since . ( days) = . . the system is highly sensitive to a sustained unbalance: even an average increase as low as % during weeks, a likely situation after outbreak peak, would nevertheless require increasing occupancy at day by %. the average length of stay (alos) in icu is an important estimate relating to the stability of the healthcare system in terms of icu bed occupancy. for instance, hypothesizing an icu alos of days in patients infected with a new emerging agent, the daily probability of a bed discharge would be / alos = / = . . this implies that whenever the rate of required admissions would exceed the % alos-dependent threshold, the global number of beds occupied or required would increase and possibly overwhelm capacity. this example demonstrates that estimating the icu alos of a population infected by an emergent virus constitutes a very critical information to modelers and decision-makers for guiding adaptations of the local capacities in the context of the outbreak. such an estimate is expected to be provided as soon as possible. however, when examining the situation within a short delay after the beginning of the outbreak, only few cases are likely to be already discharged from the icu. the patients still in icu referred to as censored cases must be considered in any unbiased estimation relating to the length of stay (los). in this study, we present a detailed examination of the timeline of the whole cohort of consecutive covid- patients admitted to a devoted icu of the zhongnan hospital of wuhan university (zhwu) in which we investigated the evolution of the alos estimation according to the accumulation of the cases, using two methods of estimation. our results indicate that even considering a last followup date corresponding to the date when two-thirds of the admitted patients would have been discharged, the icu alos estimated with the biased method would be nearly half of that issued from the unbiased method. in the light of these investigations, the estimates relating to icu los of covid- cases that have been reported to date [ ] [ ] [ ] [ ] , likely underestimate the real values. such estimates being also used in forecasting models [ ] [ ] [ ] [ ] [ ] , the present study has practical implications for improving prediction scenarios to guide public decision. this study was approved by the medical ethics committee, zhwu (clinical ethical approval no. ). the informed consent was waived by the medical ethics committee for emerging infectious disease. as in many locations, the organization of the zhwu (hubei province, people's republic of china) for managing covid- patients was subjected to several changes during the course of the covid- outbreak. first, on december , at a time when the outbreak emerged frankly, two initial icu, one depending on emergency and the other from surgery, were reorganized for constituting a single entity of beds devoted to the management of patients with covid- requiring critical care. second, on march , at a time when the outbreak had declined, all covid- icu patients were transferred to another icu in leishenshan hospital, the largest newly built facility for covid- patients with beds, while icu admissions were reorganized for other pathologies than covid- at zhwu. third, on april , leishenshan hospital was definitively closed and patients initially admitted at zhwu were retransferred to this hospital. all consecutive patients with a confirmed diagnosis of covid- by pcr and initially admitted to the abovementioned icu of beds at zhwu from december to march (n = ) were included in the study. patients admitted to this icu during this period also included consecutive patients for which there was a radiological evidence of viral pneumonia [ ] while rt-pcr test of throat swabs had remained negative for several times, and these patients were also considered as eligible for the study. last follow-up of patients was made on april , and days after the first and the last admission, respectively. the file of each patient along his/ her hospital course was cautiously reviewed, including whenever the patient was transferred to another hospital. the following data were collected for each patient: age, sex, date of admission and discharge in the hospital as well as the vital status at discharge (dead or alive), date of admission and discharge in the icu as well as the vital status at discharge (dead or alive), beginning and end dates of mechanical invasive or noninvasive ventilation procedures. whenever a patient was transferred from the icu in a given hospital to the icu of another hospital, we considered that such a continuum constituted a single icu stay. since the objective of this study was an assessment of the alos in icu of covid- patients, of the abovementioned stays were excluded from the analysis: first, one of the patients with a confirmed rt-pcr positive test had contracted covid- at the hospital while this patient was hospitalized for post-complications after a kidney transplantation, and the record file highly suggested an icu stay relating more to these complications than to covid- infection. conversely, only three of the ten patients with the radiological evidence of viral pneumonia were included in the analysis: seven patients had clinical characteristics suggesting that the icu stay might be not mainly related to covid- (e.g., liver lesions, massive cerebral infarction, …), and were therefore excluded from the study. data are expressed as mean ( % confidence interval (ci)) or median [interquartile range (iqr)], and represented according to the kaplan-meier estimator [ ] . in addition, we examined how the icu alos estimates of covid- patients issued from two estimation methods evolve and compare while the cumulative number of available stays increases along the course of the outbreak. all analyses were made with r statistical software version . . and censored data were fitted with the use of the flexsurv package. the two methods compared were the following. this first method applies a straight-forward calculation: all icu stays of the series for which the discharge date is before or equal to a given follow-up date of interest were considered (and only such stays were considered). reported alos estimate was the mean los of those already discharged patients. reported los median and quartiles were calculated on the same patients. this second method takes into account the inherent censored characteristic of longitudinal data: considering a given follow-up date of estimation, all previously admitted patients were considered, whether or not they were already discharged. a parametric distribution (e.g., exponential, gamma or weibull) was fitted to the whole set of patients. such a method for appropriately analyzing time-to-event censored data belongs to the standard framework of methods of survival analysis [ , ] . reported alos estimates, as well as los medians and quartiles, are predictions based on this parametric model. in order to demonstrate the generalizability of our results, these two methods were also compared using two simulation studies. both considered a -bed icu with as many patients admitted on day and new patients admitted as soon as the previous ones were discharged. in the first study, simulated los were sampled with replacement from the observed los in zhwu. such a simulation allows to be free from the observed schedule in practice, including the order of occurrence of the lengths of stay observed. the simulation forces the icu to be initiated in an already saturated functioning admitting covid- patients. the los of the patient still in the icu at the date of last follow-up was imputed. in the second study, los were sampled from a parametric gamma distribution in order to explore how estimates evolve with time in a situation where the true distribution is known. the median age of the patients was years [iqr - ] and ( %) were men. the time-course of the icu stays of the covid- patients is shown in fig. a . at the date of last follow-up, april , one patient was still in the icu, deaths ( %) had occurred in the icu, and the patients discharged alive from the icu were also all discharged alive from the hospital. invasive mechanical ventilation procedures concerned ( %) patients: stays involving only noninvasive ventilation concerned patients, stays involving only mechanical invasive ventilation concerned patients, and patients had shifted from one type of ventilation to another during the course of their stay. the mean and median estimates for the duration of mechanical invasive ventilation was . days ( % ci . - . ) and . days [iqr . - days], respectively. the corresponding estimates for noninvasive ventilation were . days ( % ci . - . ) and . [iqr . - . ], respectively. figure b shows the cumulative number of admissions and discharges according to time. at the date of last follow-up, over months ( days) had passed since the date of the first admission, january . figure c shows the evolution of dpe and cpe-based alos estimates according to the accumulating data that become available as time passes. exponential, . c evolution of the estimates of icu average los issued from the two methods of estimation according to the date chosen for estimation. the expected estimate is shown together with the corresponding % confidence interval. cpe, method including censored cases; dpe, method considering only stays for which the patient was already discharged from icu at the date of estimation. whenever some patients of the cohort remain treated in the icu at the date of follow-up, c indicates that dpe yields a biased underestimation of alos: discharges observed early are more likely to concern patients with a short los or conversely, the discharges occurring at the end of the process are more likely to concern patients with a long los. b illustrates the latter pattern: nine out of the first occurring discharges concern los < days, while eight out of the last occurring discharges concerned los > days weibull, and gamma distributions led to similar fits of the data-with a delayed convergence for the exponential distribution-and we retained the gamma distribution for reporting cpe. . whenever some patients of the cohort remain treated in the icu at the date of follow-up, dpe yields a biased underestimation of alos: discharges observed early are more likely to concern patients with a short los or conversely, the discharges occurring at the end of the process are more likely to concern patients with a long los. figure b , in which the los corresponding to each discharged patient is indicated along the discharge curve, illustrates this pattern: out of the first occurring discharges concern los < days, while eight out of the last occurring discharges concerned los > days. in the end, the simulations shown in additional file : appendix s demonstrate the generalizability of the biased pattern of dpe, and the unbiased pattern of cpe. figure a presents a kaplan-meier estimator and indicates that the median icu los is around days. the corresponding estimate issued from cpe is slightly higher, at . days, because the corresponding parametric fit is impacted by the substantial frequency of very long stays: fig. b shows the los distribution and out of the patients ( %) had a length of stay ≥ days. the relatively high frequency of such patients with a very long los explains why the expected estimates of alos shown in fig. c requires a substantial delay until remaining stable. interestingly, among the patients with a los ≥ days, had died while the total number of observed deaths in the cohort was . the fact that % ( / ) of the deaths observed occurred in patients who had an icu stay ≥ days also indicates that obtaining a reliable estimate of the mortality rate in the patients admitted to the icu as well as obtaining a reliable alos of the individuals dying in the icu also requires waiting a substantial delay after the beginning of the outbreak. taking the covid- outbreak as an emblematic example of the first outbreak of a threatening pandemic due to a novel infectious agent, the present study demonstrates the importance of obtaining a reliable estimate of the icu alos in such situations. the study also recalls that appropriate methods of estimation require the inclusion of censored cases in the analysis, and we also demonstrate the important bias associated with calculations only based on the stays of already discharged patients. importantly, the bias inherent of the latter method is not at all sensitive to sample size or to the consideration of factors potentially associated with icu alos value (e.g., variability from one center to another). for example, whatever the number of patients and the variability of the numerous centers involved in the studies of guan et al. [ ] based on national data from china and in the study of grasselli et al. [ ] based on hospitals from lombardy mentioned in table , the provided estimates were biased. finally, whenever patients of the population treated in the icu with a long los are observed at a substantial frequency, as was observed in the present reported series, the bias relating to inappropriate methods might be especially important. although the present study shows that alos constitutes an important parameter, we failed to find any observational study of covid- cases published in the early phase of the epidemic that reported alos. nevertheless, several of these studies had reported median estimates of icu los and such a choice is perfectly understandable: since icu los is not normally distributed, a reporting of median and iqr instead of the mean is recommended. the medians of icu los reported [ - , , ] (see table ) often concern a particular sub-population (e.g., patients who died, patients who survived), ranged from days (estimate considering six patients who died in the icu) to days (estimate reported in the same study and based on patients discharged alive from the icu) [ ] , and raise concerns in terms of the potential bias of the reported estimates (see table ). these concerns may be then extended to modeling studies [ , , , , ] that will naturally parameterize their forecasts according to the observational data reported ( table ). the data of the series reported here yielded an estimate of icu alos at . days ( % ci . - . ) and a median icu los at . days [iqr . - . ]. these estimates are well above estimates that were reported in the early phase of the epidemic. they are associated with several strengths. first the whole study time-course lasted days, enough time had passed for allowing a last date of follow-up at which all patients but one were discharged. to our knowledge, such a resulting quasi-complete distribution of the los observed in a given series of covid- cases (see fig. b ) has not been reported to date, and in addition, such a data set is indeed appropriate for assessing estimation methods since the target value of the estimate is nearly perfectly known (only one stay remained censored). second, the high values reported here are based on a reasonable sample size (n = ) and our study demonstrates that an unbiased estimate at a reasonable distance from the beginning of the epidemic is inherently higher than that issued from a biased calculation a short time after the beginning of the outbreak. nevertheless, our study also has some limitations. the study is monocentric and therefore, the extrapolation of our estimates to other settings is questionable. the gamma distribution-based cpe method allowed a reasonable alos estimate at the beginning of the epidemic, but other distributions might better fit data from other settings. because it is unbiased, the cpe method should nevertheless always be preferred, and the choice of associated simple parametric distributions should be favored as compared to more complex distributions whenever corresponding fittings are similar. the estimate issued from wuhan data is also inherently adjusted for many co-factors with a likely influence on icu los that may vary from one place to another and/or with time. for example, one may think about the impact of disease knowledge on triage decisions and on the decision to withdraw early mechanical ventilation based on refinement of prognostic factors (ethical issues), bed availability and pressure of this threatening epidemic on the organization of the healthcare system likely modifies the characteristics of admitted patients as well as various specific characteristics of the units (including cultural behaviors), accumulating experience with covid- patients likely improves management procedures according to time. ideally, estimates for different spatiotemporal settings should be based on observational data directly collected in corresponding settings for guarantying estimates appropriately adjusted with co-factors. however, such generalizability issues relating to estimate variability according to spatiotemporal conditions also stands for most studies reported to date, and devising a universal validated model able to adjust for any spatiotemporal condition worldwide is a very ambitious work, far beyond the object of the present study. the main outcome of this study is alerting the community about three elements. first, all scientists working on covid- must realize that when dealing with data relating to los, they should imperatively use appropriate methods devoted to the analysis of censored data. such methods are not original, they belong to the standard tools used in the domain of survival analysis and are easily available in any statistical software. there is no reason for avoiding their usage, and the reader will find an illustrative computer code in additional file : appendix s . an additional strength of these methods-illustrated in additional file : appendix s -is their ability to fit individual characteristics of patients with multivariable models to predict los adjusted to co-factors explicitly considered in the model formula. such a modeling strategy may for example be deployed for documenting variations between different recruitment settings or for providing estimates in specific strata of the population. a side result of the analyses made in the present study suggests that the fatality rate of covid- patients in the icu might also be underestimated, and on this topic, the present study shares many perspectives with the work of lipsitch et al. on the biases associated with the estimation of case-fatality risks [ ] . second, in the context of the first outbreak of a novel infectious agent, some estimates concerning time-to-event data such as hospital los, icu los, duration of ventilation, time of illness onset to icu admission, etc., constitute a kind of critical food required to feed forecast models and these models are very important in many issues such as exploring and comparing mitigation scenarios, or optimizing preparedness. therefore, enhancing the quality of the above-mentioned estimates is an important concern and our study suggests that there is room for such enhancements in the analyses of covid- epidemic. third and to conclude, whenever the estimates reported in this study would be generalizable to other settings, then this is bad news: long icu los as reported here imply that occupied beds remain unavailable for a long time and this adds additional pressure to the surge in icu beds encountered in many places worldwide. based on this complete series of consecutive cases together with simulated cases, the present work demonstrates that icu_alos estimates used in most models to date may be importantly underestimated. in such a context of novel infectious agent, this work advocates for an urgent application of widespread survival analysis tools to properly estimate icu_alos and other critical parameters relying on censored time-toevent data. accurate estimation of these parameters, on which rely forecast models, is crucial to ensure consistency of mitigation and preparedness scenarios, as attested by the worldwide concern over icu bed occupancy in the current covid- crisis. the funders had no role in: study design; collection, analysis, and interpretation of data; writing of the manuscript; preparation of the manuscript world health organization impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand response team point quotidien infection au nouveau coronavirus (sars-cov- ): nombre de personnes actuellement en réanimation ou soins intensifs pour covid- baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region italy clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan china clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study projecting hospital utilization during the covid- outbreaks in the united states locally informed simulation to predict hospital capacity needs during the covid- pandemic the epidemic calculator modeling covid- spread vs healthcare capacity ihme covid- health service utilization forecasting team, murray cj. forecasting covid- impact on hospital bed-days, icu-days, ventilatordays and deaths by us state in the next months. medrxiv radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study survival analysis: a self-learning text survival and event history analysis: a process point of view clinical characteristics of coronavirus disease in china clinical features and short-term outcomes of patients with corona virus disease in intensive care unit potential biases in estimating absolute and relative case-fatality risks during outbreaks publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the decision of performing the study emerged from informal discussions involving nl, xz, fc, br, yz, and gh. study conception and design: nl and gh. data acquisition: xz and yz had full access to all of the raw data in the study and can take responsibility for the integrity of the data. analysis: nl and gh. interpretation of data: nl, xz, fc, br, yz, and gh. first draft of the article: nl and gh. all authors read and approved the final manuscript. this study has benefited from the support of the national natural science foundation of china ( to dr. xianlong zhou) and from the emergency response project of hubei science and technology department supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : appendix s . simulation study.additional file : appendix s . unbiased average length of stay estimation-an illustrative example. all data used in this article are explicitly shown in figs. and of the article. any request for additional details must be sent to drs. zhao and zhou. this study was approved by the medical ethics committee, zhwu (clinical ethical approval no. ). the informed consent was waived by the medical ethics committee for emerging infectious disease. not applicable. prof. carrat reports personal fees from sanofi, personal fees from imaxio, outside the submitted work. the other authors have nothing to disclose. key: cord- -sjvqjoye authors: gaudet, alexandre; martin-loeches, ignacio; povoa, pedro; rodriguez, alejandro; salluh, jorge; duhamel, alain; nseir, saad title: accuracy of the clinical pulmonary infection score to differentiate ventilator-associated tracheobronchitis from ventilator-associated pneumonia date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: sjvqjoye background: differentiating ventilator-associated tracheobronchitis (vat) from ventilator-associated pneumonia (vap) may be challenging for clinicians, yet their management currently differs. in this study, we evaluated the accuracy of the clinical pulmonary infection score (cpis) to differentiate vat and vap. methods: we performed a retrospective analysis based on the data from independent prospective cohorts. patients of the tavem database with a diagnosis of vat (n = ) or vap (n = ) were included in the derivation cohort. patients admitted to the intensive care centre of lille university hospital between january , and december , who had a diagnosis of vat (n = ) or vap (n = ) were included in the validation cohort. the accuracy of the cpis to differentiate vat from vap was assessed within the cohorts by calculating sensitivity and specificity values, establishing the roc curves and choosing the best threshold according to the youden index. results: the areas under roc curves of cpis to differentiate vat from vap were calculated at . ( % ci [ . – . ]) in the derivation cohort and . ( % ci [ . – . ]) in the validation cohort. a cpis value ≥ was associated with the highest youden index in both cohorts. with this cut-off, sensitivity and specificity were respectively found at . and . in the derivation cohort, and at . and . in the validation cohort. conclusions: a cpis value ≥ reproducibly allowed to differentiate vat from vap with high specificity and ppv and moderate sensitivity and npv in our derivation and validation cohorts. ventilator-associated lower respiratory tract infections (va-lrti), including ventilator-associated tracheobronchitis (vat) and ventilator-associated pneumonia (vap), are the most frequent infectious complications in intensive care units (icu), concerning about % of critically ill subjects undergoing mechanical ventilation [ ] . their diagnosis currently relies on symptoms of lower respiratory tract infection in patients intubated for more than h with a positive culture of lower respiratory microbiological sampling. in addition to these criteria, the presence of a new infiltrate on chest radiography allows to make the diagnosis of vap. by contrast, vat is characterized by the combination of the above-mentioned criteria without new radiographic infiltrates [ ] . the occurrence of vap is associated with increased mortality, longer duration of mechanical ventilation and length of stay in the icu. on the other hand, the diagnosis of vat seems to be linked with lower levels of mortality than vap, even though being associated with increased length of mechanical ventilation and icu stay [ ] . the management of vap currently relies on antimicrobial therapy, whereas current guidelines do not recommend the administration of antibiotics in vat, making the distinction between these two entities a crucial point [ ] . although theoretically based on clearly defined criteria, differentiating vat and vap may sometimes be challenging for the physician. indeed, chest radiographies performed in the context of icu often lead to multiple artefacts, additionally to numerous causes of non-infectious radiological opacities making the diagnosis of vap tricky. in addition, a lack of sensitivity of chest radiography has been reported for the detection of vap, thus leading to a likely underestimation of this diagnosis in mechanically ventilated patients [ ] [ ] [ ] . several tools have been developed to improve the detection of vap. amongst them, the clinical pulmonary infection score (cpis) is a daily routine parameter-based score with moderate to good accuracy in the detection of vap. this score, originally described by pugin et al, has been declined in a simplified version, allowing its easier appliance by physicians at patient's bedside [ , ] . based on the results of a single study, recent guidelines on the management of hospital-acquired pneumonia and vap suggest that a cpis score ≤ should lead to the early discontinuation of antimicrobial therapy, being associated with a low probability of pneumonia [ , ] . considering these observations, the use of the cpis in patients with microbiologically confirmed va-lrti might be proposed as a helpful tool for the early detection of vap. however, to the best of our knowledge, the evaluation of the cpis in this indication has never been reported yet and would be of significant interest. furthermore, such an evaluation should be preferentially performed in independent cohorts to assess its reproducibility, given the heterogeneity in the performances of cpis for the diagnosis of vap in ventilated patients [ ] , and because this score was not initially developed to distinguish vat from vap. therefore, we aimed in this study to evaluate the accuracy of the cpis to differentiate vat from vap in independent cohorts of patients with microbiologically confirmed va-lrti. this is a retrospective study based on the analysis from the tavem database [ ] and of a cohort of patients admitted in a single mixed icu during a -year period. the tavem study is a large prospective multinational observational study conducted in icus in europe and south america. details about the design and patients of the tavem study have been previously published [ ] . in our study, patients from the tavem database with a diagnosis of va-lrti were included in the derivation cohort. patients admitted in the single mixed icu of the lille university hospital between january and december and with a diagnosis of va-lrti were included in the validation cohort. patient demographic characteristics, severity scores, comorbidities, primary diagnoses, and prior antibiotic exposure were recorded at baseline for all patients. further, data about clinical, biological and radiological diagnostic criteria for va-lrti, microbiological diagnostic procedures, bacteriological findings, degree of severity on the onset of infection, antibiotic use and clinical outcomes were obtained. the diagnosis of va-lrti was based on the presence of at least of the following criteria: body temperature of more than . °c or less than . °c, leucocyte count greater than , cells per μl or less than cells per μl, and purulent endotracheal aspirate. microbiological confirmation was needed for all episodes of infection, with the isolation in the endotracheal aspirate of at least cfu per ml, or in bronchoalveolar lavage of at least cfu per ml. vat was defined with the above-mentioned criteria with no radiographical signs of new pneumonia. conversely, vap was defined by the presence of new or progressive infiltrates on chest radiograph. a modified version of the cpis was used in this study, as previously published in the literature (additional file ) [ ] . notably, we did not consider cultures of tracheal aspirate; leucocyte categories were reduced to two; three categories were used for the aspect of sputum; tracheal secretions were classified as few, moderate, large, and purulent. the cpis score was calculated at the time of microbiological sampling for clinical suspicion of va-lrti by retaining for each variable the maximal attributable number of points over the past hours. the primary aim of this study was to evaluate the accuracy of the cpis to differentiate vat from vap in patients with microbiologically confirmed va-lrti. categorical variables were expressed as numbers (percentages) and compared using chi square test or fisher's exact test, as appropriate. normality of distribution of continuous variables was checked graphically and using the shapiro-wilk test. skewed continuous variables were presented as medians (interquartile ranges), and compared using mann-whitney u tests. normally distributed continuous variables were presented as means (sd), and compared using student's t tests. correlations between skewed continuous variables were assessed using spearman's rank correlation tests, and regression lines were displayed using simple linear regression method. to assess the diagnostic ability of cpis to differentiate vat from vap, we performed a receiver operating characteristics (roc) analysis for the diagnosis of vap in both derivation and validation cohorts. we computed the area under the roc curve (auc) and the sensitivity, specificity, positive and negative predictive values (ppv and npv) as well as positive and negative likelihood ratios for different cut-off values. the best cut-off for the discrimination between vap and vat was determined according to the youden index. all statistical tests were two-tailed and p values < . were considered statistically significant. statistics department of lille university hospital performed all data analyses using sas software package, release . (sas institute, cary, nc, usa). three hundred twenty patients with vat and patients with vap were included in the derivation cohort. seventy patients with vat and patients with vap were included in the validation cohort. percentage of male and percentage of cirrhosis were higher, whilst age was lower in patients with vap compared to patients with vat in the derivation cohort. sofa score was higher and percentage of heart failure was lower in patients with vap compared to patients with vat in the validation cohort. appropriate initial antimicrobial therapy was more frequent in vap than in vat in the derivation cohort, and less frequent in vap compared to vat in the validation cohort ( table ) . comparisons of baseline patients characteristics between derivation and validation cohorts are shown in additional file . data are presented as number (%) or mean (sd) copd chronic obstructive pulmonary disease, saps simplified acute physiology score, sofa sequential organ failure assessment, vap ventilator-associated pneumonia, vat ventilator-associated tracheobronchitis p value < . is indicated in italic characters clinical outcomes in the derivation and validation cohorts are shown in table and additional file . icu mortality was higher in patients with vap compared to patients with vat in the derivation cohort. the analysis of microbiological findings revealed a higher frequency of enterobacter spp. in patients with vap compared to patients with vat in the validation cohort. conversely, citrobacter freundii was found more frequently in vats than in vaps in the validation cohort ( table ) . comparisons of microbiological findings between derivation and validation cohorts are shown in additional file . cpis values ranged from to for patients with vat and from to for patients with vap in the derivation cohort. in the validation cohort, cpis values ranged from to for patients with vat and from to for patients with vap. the distribution of cpis values was significantly lower in patients with vat than in those with vap in the derivation cohort with median values of ( - ) vs ( - ) (p < . ) as well as in the validation cohort ( ( - ) vs ( - ) (p < . )) ( fig. ) . roc analysis showed aucs at . ( % ci [ . - . ]) in the derivation cohort and . ( % ci [ . - . ]) in the validation cohort (fig. ) . performances of the cpis for the diagnosis of vap at different cut-offs are summarized in table . a cpis value ≥ was associated with the highest youden index in both cohorts. with this cut-off, sensitivity and specificity were respectively found at . and . in the derivation cohort, and at . and . in the validation cohort. a cpis value ≥ was found in patients of the validation cohort and amongst them, were true vaps (ppv = . ). in the derivation cohort, patients had (fig. ) . in the derivation cohort, inappropriate antimicrobial therapy was associated with a longer duration of mechanical ventilation in patients with a cpis value ≥ , whilst no difference between groups was found in subjects with a cpis value < (table ). comparisons of clinical outcomes according to the appropriateness of antimicrobial therapy in vat and vap in derivation and validation cohorts are shown in additional file . in this study, a cpis value ≥ appeared as the best cutoff according to the youden index, with a high specificity and a moderate sensitivity, with similar results in both derivation and validation cohorts. as far as we know, this is the first study to explore the accuracy of cpis for the diagnosis of vap amongst patients with va-lrti. cpis has been widely described as a helpful tool, with a moderate accuracy for the diagnosis of vap, a best cut-off value of in most studies, and pooled estimates for sensitivity and specificity at . and . , respectively [ ] . the question of early identifying patients who will develop a diagnosis of vap may be critical, as therapeutic managements of vat and vap currently differ. indeed, current guidelines recommend that vap should be treated with appropriate antimicrobial therapy, by contrast with vat for which such a treatment remains not recommended [ , ] . in that view, considering a cpis value ≥ as a criterion for the early initiation of antimicrobial therapy may appear clinically relevant, as this cut-off was associated with good specificities and ppvs > . in both cohorts. furthermore, a cpis value ≥ was found in / ( %) and / ( %) patients with vaps in our derivation and validation cohorts, respectively, suggesting that this threshold may allow an early diagnosis in almost half cases of vap. conversely, we may note the moderate to poor npv of the cpis to exclude the diagnosis of vap. accordingly, it appears that using the cpis in subjects with clinical suspicion of va-lrti and positive microbiological sampling should mostly be considered for the early initiation of antibiotics in patients with a cpis value ≥ . however, these considerations must be taken with caution. first, because appropriate antimicrobial therapy in patients with cpis ≥ was poorly associated with favourable outcomes in our cohorts, yet this result might be a consequence of the differences in characteristics between patients receiving appropriate and inappropriate antibiotic treatments. second, the question of initiating antibiotic treatments in patients with vat remains unclear. indeed, a continuum between vat and vap cannot be ruled out, as a higher risk of pneumonia was reported in patients with vat in the tavem study [ ] . in addition, data from this cohort suggest that the risk of progression from vat to vap would be reduced in patients receiving antibiotic treatment. on the other hand, current french and international guidelines do not address the initiation of antibiotics in vat, because of a lack of evidence supporting this strategy [ ] . thus, further investigations are warranted to clarify whether patients with vat should benefit or not from antimicrobial therapy. one apparently surprising result of our study was the % rate of patients with cpis values ≥ in vats. this might be explained by the fact that our study was restricted to patients with symptoms of lower respiratory tract infections. this is likely to have resulted in overall greater cpis values in our population than usually reported, especially in patients without vap [ ] . as a consequence, a more intense clinical presentation seems required to accurately segregate vaps from vats than to distinguish vaps from patients without respiratory infections. this might partly explain the optimal cut-off found at in our study, which is higher than the points threshold usually reported in the literature [ ] . in contrast, we report cpis values found at or in several patients with vaps and vats in both cohorts. this result is actually reflecting the uncomplete clinical presentations initially observed in some patients. in these, the symptoms could initially include a mild increase of body temperature without reaching . °c, the appearance of few tracheal secretions, or a moderate worsening of the pao /fio ratio without falling below , thus motivating the respiratory microbiological sampling, although the cpis was still calculated at or by then. however, all these patients eventually reached the criteria for va-lrti, with a worsening of their symptoms, thus completing their clinical presentation. this frequent progression at the initial stage of va-lrti raises the question of whether the calculation of cpis at a single time-point can give enough information to distinguish vap from vat. the evaluation of the relationship between cpis calculated at the time of clinical suspicion of va-lrti and variations of cpis over h before that time-point (delta cpis) in our derivation cohort brings some interesting insights about that question. this analysis reveals that nearly all patients with a cpis value ≥ also had a delta cpis ≥ and that cpis was subsequently correlated to delta cpis in vat and in vap (additional file ). furthermore, delta cpis does not seem to show greater accuracy than cpis to differentiate vat from vap (additional file ). these results convey the idea that subjects with greater cpis are not only exhibiting marked features of respiratory infection, but are also worsening their symptoms, thus supporting the reliability of the cpis measured at a single time-point to discriminate vats from vaps. other parameters than the cpis might be proposed to improve the early diagnosis of vap. vap seemed to be associated with a higher mortality in icu than vat, yet this result was not statistically significant in the validation cohort. this result suggests that a diagnosis of vap might be associated with more severe organ failures, and especially with more severe levels of hypoxaemia. this hypothesis is supported by the results of the tavem study, showing that significantly more patients with vap had an episode of worsening gas exchange than did those with vat [ ] . therefore, severity scores like sofa, calculated at the time of the clinical suspicion of va-lrti, could help to improve the early detection of vap, particularly through evaluation of the respiratory sofa. a similar strategy has already been developed through the infection probability score, although this score does not apply specifically to vap but to nosocomial infections in general [ ] . furthermore, such a strategy has never been evaluated specifically for va-lrti. routine biomarkers like crp and pct have been evaluated for the identification of vap, with variable diagnostic performances. luyt et al. reported a poor accuracy of pct for the diagnosis of vap, with roc aucs respectively found at . and . for d- pct and pct increase. to be noted that adjunction of pct did not significantly improve the accuracy of the cpis for the diagnosis of vap in this study, with an auc rising from . for cpis alone to . for cpis combined with pct [ ] . in another report, charles et al. showed good performances of pct variations for the diagnosis of nosocomial infections, with aucs > . in roc analysis and similar results for the diagnosis of vap. in this work, pct variations were above all associated with a good specificity and high ppvs [ ] . on the other hand, povoa et al. showed a moderate performance of crp for the diagnosis of vap, with aucs > . for variations of crp in their roc analysis [ ] . furthermore, at the day of vap diagnosis, they observed that a single measurement of crp was useful in particular for the exclusion of vap diagnosis. beside these routine biomarkers, some authors have investigated the potential usefulness of strem- , yet with disappointing results showing very poor accuracy for the diagnosis of vap [ , ] . these data underline the potential utility of these biomarkers in differentiating vat from vap. however, their moderate accuracy when taken as single parameter highlights the hypothetical interest of a mixed evaluation integrating one or several of these variables in a cpisbased score. the distinction between vat and vap currently relies on the presence of at least one new infiltrate on the chest radiography. however, the relevance of this criterion remains questionable, given its low accuracy in diagnosing microbiologically confirmed vap amongst critically ill subjects undergoing mechanical ventilation [ ] . this inaccuracy mainly results from the difficulties to distinguish infiltrates of infectious cause from other aetiologies, like pleural effusions, cardiac overload or atelectasis, which are frequently present in icu patients [ ] . in that view, lung ultrasound has been proposed as a promising tool for the diagnosis of vap, and could thus be considered to distinguish vat from vap, yet its utility remains limited because of its poor inter-operator reproducibility [ ] . computed tomography (ct) could also be proposed to enhance the detection of lung infiltrates. indeed, self et al. reported that only . % of the patients presenting to ed with opacities on ct had images of pneumonia detected on chest radiography [ ] . therefore, ct could allow a better differentiation between vat and vap. however, its greater cost, associated with the necessity to transport patients, and higher exposure to radiations limit its use in routine clinical practice. all these tools could improve the accuracy of the cpis and should probably be assessed in a future updated version of this score. our study has several limitations. first, this was a retrospective analysis, thus limiting the parameters that could be studied in our cohorts. above all, studying the accuracy of inflammation biomarkers like crp or pct would have been interesting, but could not be performed because these parameters were not measured in a sufficient number of patients in our validation cohort. second, this study was performed in patients with microbiologically confirmed va-lrti, limiting the applicability of our results at the patient's bedside, because of the frequent delay between processing of the microbiological sampling and culture positivity. third, evaluating the cpis to distinguish vat from vap might appear questionable in our study, as the radiographic criterion is part of the items required for the calculation of this score. nevertheless, it must be noted that the cpis was calculated once for all at the time of microbiological sampling in the respiratory tract, which corresponded to the moment of the clinical suspicion of va-lrti. this is to oppose the methods used to retrospectively classify patients between vat and vap, with all the biological, clinical and radiological data available to make a final diagnosis. this last point must be considered regarding the frequency of uncomplete initial presentation with initial absence of radiographic signs, representing more than % of vap in the study performed by ramirez et al. [ ] . fourth, the population of our study included a lower percentage of surgical admissions in the validation cohort than in the derivation cohort. this might have interfered with our results, as a poor accuracy of cpis has been reported in surgical patients, because non-infectious causes of lung injury may represent a confounder in this population [ , ] . fifth, the rates of appropriate initial antibiotic treatments were significantly different between vaps and vats in both cohorts. accordingly, we could not draw any conclusion regarding the benefit of appropriate antimicrobial therapy in patients with a cpis value ≥ . sixth, roc analysis showed a lower auc of cpis in our validation cohort, thus underlining a weaker overall accuracy in this population. finally, lung infiltrates were probably missed in some patients with vap, given the reported lack of sensitivity of chest radiography for the detection of pneumonia [ , ] . however, the use of chest radiography allowed us to diagnose vat and vap using the same criteria than in the tavem study. accordingly, our definitions of vap and vat are consistent with those in which a difference in mortality rates was reported [ ] . further explorations in a larger prospective multicentre study are needed to confirm our findings. in patients with evidence of va-lrti, a cpis value ≥ allowed the early diagnosis of half cases of vap with specificity and ppv above % in our derivation and validation cohorts. the cpis might thus be considered as a helpful tool to drive the early initiation of antimicrobial therapy in patients with va-lrti. incidence and prognosis of ventilator-associated tracheobronchitis (tavem): a multicentre, prospective, observational study international ers/esicm/escmid/alat guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (hap)/ventilator-associated pneumonia (vap) of the the chest radiograph in critically ill surgical patients is inaccurate in predicting ventilator-associated pneumonia the clinical value of daily routine chest radiographs in a mixed medicalsurgical intensive care unit is low from starting mechanical ventilation to ventilator-associated pneumonia, choosing the right moment to start antibiotic treatment diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. a proposed solution for indiscriminate antibiotic prescription diagnostic accuracy of clinical pulmonary infection score for ventilator-associated pneumonia: a meta-analysis management of adults with hospital-acquired and ventilatorassociated pneumonia: clinical practice guidelines by the infectious diseases society of america and the infection probability score (ips): a method to help assess the probability of infection in critically ill patients usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report biomarker kinetics in the prediction of vap diagnosis: results from the biovap study soluble triggering receptor expressed on myeloid cells- (strem- ) as a diagnostic marker of ventilator-associated pneumonia soluble triggering receptor expressed on myeloid cells- in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia lung ultrasound for diagnosis and monitoring of ventilator-associated pneumonia high discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ed patients: implications for diagnosing pneumonia the futility of the clinical pulmonary infection score in trauma patients screening for ventilator-associated pneumonia in the surgical intensive care unit: a single-institution analysis of , lower respiratory tract cultures publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . authors' contributions ag, im-l, pp, ar, js and sn contributed to acquisition of data for the work. ag, ad and sn contributed to analysis of data for the work. ag and sn contributed to interpretation of data for the work. all authors have revised this work critically for important data, given their final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. all authors read and approved the final manuscript. the tavem study group included the following contributors:ignacio martín- none. the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. centers participating to the tavem study either received ethics approval from their institutions or ethics approval was waived (institutional review board number ). not applicable. sn reports personal fees from msd, pfizer, gilead, bio rad, and biomerieux, outside the submitted work; other authors have no competing interest to disclose. the authors declare that they have no competing interests. key: cord- -n x gcn authors: hurtado, daniel e.; erranz, benjamín; lillo, felipe; sarabia-vallejos, mauricio; iturrieta, pablo; morales, felipe; blaha, katherine; medina, tania; diaz, franco; cruces, pablo title: progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: n x gcn background: protective mechanical ventilation (mv) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ards) patients. in ards lungs without mv support, the mechanisms and evolution of lung tissue deformation remain understudied. in this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under mv. methods: lung injury was induced by lung lavage in murine subjects, followed by h of spontaneous breathing (sb-group) or h of low v(t) mechanical ventilation (mv-group). micro-ct images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. three-dimensional regional strain maps were constructed, from which a region-of-interest (roi) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. results: after h of ventilation, regional strain levels were significantly higher in . % of the rois in the sb-group. significant increase in regional strain was found in . % of the rois in the mv-group. progression of regional strain was found in % of the rois in the sb-group, whereas the mv-group displayed strain progression in . % of the rois. progression in regional strain heterogeneity was found in . % of the rois in the sb-group, while the mv-group resulted in . % of the rois showing significant changes. deformation progression is concurrent with an increase of non-aerated compartment in sb-group (from . % ± . % to . % ± . %), being higher in ventral regions of the lung. conclusions: spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. in contrast, low v(t) mv prevents regional strain and heterogeneity progression in injured lungs. supraphysiological levels of pulmonary tissue deformation during mechanical ventilation (mv), measured in terms of relative volume change, are associated with worse outcomes during acute respiratory failure [ ] [ ] [ ] . tissue deformation can be expressed as global strain, can be defined as the ratio of tidal volume (v t ) over the endexpiratory lung volume (eelv) for the lung. global strain has been used to determine safe thresholds of v t to prevent secondary lung injury (i.e., ventilator-induced lung injury) [ ] . however, lung damage can occur in patients under mv, even if they are ventilated within the defined global safety limits. lung deformation heterogeneity and regional overdistention have been proposed as promotor mechanisms in these conditions. a spatial correlation between areas of increased regional strain and areas of tissue inflammation has been found in a high global strain model, demonstrating the potential role of regional biomechanical behaviors in the progression of lung injury [ ] . considering these findings, a better understanding of the spatiotemporal progression of regional strain and heterogeneity may be the key to avoid progression of damage to the lungs during respiratory failure [ ] . clinicians are now concerned by the impact of spontaneous breathing with or without mv during acute respiratory failure. experimental and clinical studies have demonstrated that vigorous spontaneous breathing overlapping with mv may worsen lung injury [ ] [ ] [ ] [ ] . however, in non-intubated subjects with lung injury and spontaneous unregulated ventilatory efforts, regional forces generated by the respiratory muscles may lead to injurious effects on a regional level and induce the progression of the lung injury, a phenomenon known as patient selfinflicted lung injury [ ] . with these thoughts in mind, we designed this study of experimental lung injury to understand how regional lung inflation patterns evolved in time in spontaneousbreathing subjects and in under controlled low v t mv. we hypothesize that regional deformation in lung injury progresses in time in spontaneous-breathing lungs, whereas it remains uniform in subjects under controlled mv. the study protocol was approved by the universidad andres bello bioethics committee. sprague-dawley rats (sex paired) were considered for this study. the rats were maintained in humidity, light, and temperature-controlled environment inside a dedicated animal research facility. food and water were provided ad libitum. after inhalatory induction with % isoflurane (aesica queenborough ltd., uk), the rats were anesthetized by an intraperitoneal injection of ketamine ( mg − kg − , drag pharma invetec s.a.) plus xylazine ( mg − kg − , alfasan, woerden-holland). after tracheal instillation with % lidocaine (drag pharma, santiago, chile), tracheal intubation was performed with a g bd angiocath ® catheter (becton-dickinson infusion therapy systems inc., utah, usa). for intubation, an adequate level of anesthesia was assumed if the pedal reflex was absent. otherwise, a second ketamine ( mg − kg − ) plus xylazine ( mg − kg − ) dose was administered. lung injury was induced by saline lavage, as previously reported [ ] , but we adapted the model to maintain a group without mv during the observation period after lung injury. in short, each animal was placed in supine decubitus after intubation, and one instillation of . ml − kg − of warm normal saline was flushed in the airway. the residual fluid was suctioned from the airway (surfactant depletion). after lavage, the animals were stabilized for an average time of min with a volumecontrolled mv strategy, using a v t of ml kg − , positive end-expiratory pressure (peep) of cmh o, i:e ratio : , respiratory rate (rr) of breaths per minute and an inspiratory fraction of oxygen (fio ) of , which was delivered by a ventelite ® small animal ventilator (holliston, ma, usa). block randomization was used to assign the animals to the spontaneous breathing group (sb-group) and the low v t controlled mv group (mv-group) after induction of lung injury and stabilization. extubation in the sb-group was performed after stabilization when spontaneous respiratory effort was detected during a gradual lowering of respiratory frequency; then, animals were supported with a fio of in the oxygen chamber (somnosuite ® for rats, kent scientific, torrington, ct, usa). for the mvgroup, mv was performed using the following parameters: v t ml kg − , peep cmh o, i:e ratio : , rr of breaths per minute and fio . all subjects were placed in a prone position for the rest of the study. rectal temperature, electrocardiogram, rr, and oxygen saturation (spo ) were monitored and recorded using the small animal physiological monitoring system (holliston, ma, usa). body temperature was maintained at ± °c through the controlled heating surface of the system. after min of clinical stability in both groups, the vital signs were registered, and the first set of images was acquired. then, the subjects were observed and monitored for h. after this period, a second set of images was obtained. during the observation phase, dissociative anesthesia was adjusted to suppress motor activity in the sb-group and to suppress the respiratory effort and ventilatory asynchrony in the mv-group. initially, the sbgroup consisted of nine subjects, and the mv-group consisted of six subjects. at the end of the study, the animals were killed by intravenous administration of a lethal dose of thiopental ( mg/kg, richmond laboratories, buenos aires, argentina). a schematic depicting the experimental protocol can be found in additional file : figure s . micro-computed tomography (micro-ct) images were acquired using a commercial skyscan in vivo micro-ct scanner (bruker microct, kontich, belgium). images at end-of-expiration (ee) and end-of-inspiration (ei) were acquired at the beginning (t ) and the end (t ) of the ventilation stage. the scanner includes a physiological monitoring system to track the breathing of the subject in order to deliver time-resolved four-dimensional ( d) image sequences. in the sb-group, respiratory gating based on the thorax movement was employed to reduce the effect of motion artifacts [ ] , while in the mv-group, the acquisition was controlled by the mechanical ventilator cycles. scans were performed using a source voltage of kv and a source current of μa. the isotropic voxel resolution was μm. the retrospectively synchronized "listmode" scan was performed with an exposure time of ms, a scan rotation of ° and a step of . °. the entire scanning procedure took approximately min. micro-ct images were then postprocessed using the software provided by bruker (nrecon, tsort, data-viewer, and ctan) to increase the signal-to-noise ratio and to enhance the contrast. ring artifact and hardening filters were employed to improve the quality of the acquired images. median and unsharp mask filters were applied to reduce the noise and enhance the definition of boundaries in the images. lung images were segmented using the active-contour method implemented in the itk-snap software (university of pennsylvania, philadelphia, usa) [ ] . manual corrections were performed when necessary, and the resulting segmented images were carefully checked by independent clinical experts to assure anatomically correct structures. two masks for ee and ei images were generated during the segmentation step. a first mask, denoted as whole-lung mask, considered the whole-lung domain. a second mask, denoted as aerated-lung mask, only considered lung regions that belonged to compartments classified as poorly aerated, normal, and hyperaerated, according to their values of hounsfield units and the ranges defined for these compartments that have been reported in the literature [ ] [ ] [ ] [ ] . non-aerated regions were excluded from this second mask. the aerated-lung mask was then used to compute the end-of-inspiration lung volume (eilv) and end-of-expiration lung volume (eelv). tidal volume was defined as v t = eilv − eelv. the global strain was calculated as v t /eelv, and minute ventilation was determined as v min = rr × v t . the distribution of aeration compartments was computed from the whole-lung masked images, dividing the lung in four compartments according to the hu intensity, as described above. aeration distribution was reported as stacked bar charts using the percentage of the total lung volume that each compartment occupied. besides, for the sb-group, the aeration distribution of the dorsal region and of the ventral region was computed from dividing the lung image into two subregions of equal volume along the dorsal-ventral direction. the image-based biomechanical analysis was performed following the approach introduced by our group in previous publications [ , ] . in brief, the niftyreg library [ ] was employed to perform image registration between aerated-lung masks of ee and ei to obtain the displacements between the expiratory and inspiratory states of the lung. a d tetrahedral finite-element mesh was created from the aerated-lung mask at ei for each lung of all subjects. the displacement of the mesh from ee to ei allowed for the calculation of local volumetric strain. the biomechanical approach used in this work has been summarized in non-technical terms elsewhere [ ] . additional file : figure s shows a schematic diagram of the sequential steps performed for obtaining the d regional lung strain maps, which are indicative of local parenchymal stretching [ , ] . to allow for regional comparison between groups, lungs in each subject were divided into ten segments with approximately equal volumes along the apical-basal (ab) direction and into ten segments along the dorsal-ventral (dv) direction. by intersecting all ab and dv segments, we constructed a matrix of × regions of interest (rois) that are independent of one another. during this procedure, some ab and dv segments did not intersect, and therefore some of the rois were void. weighted mean and standard deviation values of regional volumetric strain were computed for each roi, where the sample includes tetrahedra contained in each roi, and weighting is performed according to each tetrahedron volume. the time evolution of the regional volumetric strain at each roi was studied by means of the regional strain progression index (spi), defined for each roi as spi = ( + roimean strain at t )/( + roi-mean strain at t ). we note that spi is a relative measure of deformation progression. an spi = implies no evolution of regional strain, an spi > is related to temporal progression (amplification) of regional strain, and spi < implies a reduction of regional strain over time. to evaluate the dispersion of regional strain in an roi, we defined the regional strain heterogeneity index (shi) as the coefficient of variation of the roi strain distribution, which is expressed in terms of volumetric change, i.e., shi = ( + roi standard deviation)/( + roi-mean). a wilcoxon signed-rank test was employed to assess intra-group differences in time for global physiologic parameters such as global strain, spo , eelv, v t , rr, and v min , as well as those parameters in the lung aeration compartments. the time progression of regional deformation in each roi was studied by means of the wilcoxon signed-rank test to assess absolute differences in regional strain between t and t . relative differences in spi were studied by means of a mann-whitney u-test to detect if spi was different from . . the feltz-miller asymptotic test for the equality of coefficients of variation from k populations [ ] was employed to independently detect differences of shi between t and t for each roi. values are expressed as the mean ± sem. all calculations were done using the software for statistical computing r version . . (http://www.r-proje ct.org/). surfactant depletion resulted in severe respiratory failure during the stabilization phase, with an s/f ratio ± mmhg for all subjects. statistical and image analysis was carried out using five subjects in the sb-group and five subjects in the mv-group due to the following considerations: (i) mortality in the sb-group was high, with three out of nine subjects dying before completing the observation period and image acquisition; and (ii) the ct images acquired in one animal of each group displayed a notorious alteration of the thoracic-abdominal region, preventing a reliable analysis. the group weights were ± g and ± g for the sb-group and the mv-group, respectively. table reports the physiologic parameters (spo , rr, v t , v min , eelv) and global strain for both groups under study. additional file : table s shows the individual physiologic data for both groups. no significant changes were detected between t to t in any of the groups. the distribution of lung aeration is shown in fig. . there were significant changes in time in lung tissue aeration in the sb-group, decreasing normal lung tissue and increasing non-aerated tissue at t compared to t . there were no significant differences in mv-group. additional file : figure s shows the dorsal and ventral distributions of aeration compartments in the sb-group at t and t . when analyzing the changes in aeration in the sb-group, we found an increase of . % in the non-aerated ventral region and an increase of . % in the nonaerated dorsal region. additional file : figure s shows ct images at ee and ei for t and t in sb-group. at ee, we observe the collapse progression over time, particularly at the ventral regions. at ei, we observe a progression of aeration in the basal-dorsal region. roi array maps reporting roi-mean regional volumetric strain for the sb-group and mv-group at t and t are shown in fig. (see fig. a for a sketch depicting the apical-basal and ventral-dorsal directions). when comparing rois in t and t , there was a significant table physiologic data for the experimental groups at the beginning and at the end of the ventilation stage, either for sb-group or mv-group eelv, v min , v t , and global strain were obtained from image analysis of μ-ct images no significant changes were detected between t to t in any of the groups regional strain in the sb-group at t . c regional strain in the mv-group at t . d regional strain in the sb-group at t . e regional strain in the mv-group at t . significant within-subject differences are denoted by * (p < . ) increase in regional volumetric strain in out of rois ( . %), which were predominantly located in the basal-dorsal quadrant (fig. b, d) . in contrast, in the mv-group, only out of rois ( . %) was found to be significantly different between t and t (fig. c, e) . additional file : figure s shows the d regional volumetric strain maps for representative subjects of the sbgroup and mv-group at t and t . when analyzing volumetric regional strain over time, all rois in the sb-group ( out of ) had a significant spi greater than , showing progression (fig. a) . a spatially homogeneous progression trend is therefore observed for the whole lung in this group. in contrast, in out of rois of the mv-group, spi was not different than , meaning an absence of progression of volumetric strain. roi array maps reporting the roi-mean spi for the sb-group and mv-group are shown in fig. . heterogeneity of regional deformation was assessed through the shi, for which roi arrays are reported in fig. . in the sb-group, we found a significant increase in time in shi in out of rois ( . %) (fig. a, c) . in the mv-group (fig. b, d) , only out of rois resulted in a significant increase of shi between t and t ( . %). in this work, we studied the lung regional strain distribution, heterogeneity, and deformation progression in subjects spontaneously breathing and subjects on controlled low-v t mv in a murine lung-injury model. we found that a significant progression in regional volumetric strain and heterogeneity was observed after h of spontaneous breathing in injured lungs. changes in lung regional strain during spontaneous breathing were concurrent with the tomographic progression of the nonaerated-tissue compartment of the lung and a reduction of the normal-tissue compartment, in accordance with de-recruitment phenomenon, with collapse progression being higher in ventral regions of the lung. in contrast, the mv-group had limited progression of the regional strain and heterogeneity at the end of the study. a key finding of our study is that regional strain significantly progressed in the sb-group, but did not result in major changes in the mv-group. we note that in the sb-group, global strain increased in roughly % from t to t , but due to intra-group variability and the small sample size, this mean increase did not result in significant differences. while this situation is a limitation of the study, it also highlights the high sensitivity of regional deformation analysis in detecting strain progression when compared to global strain. another interesting finding is that strain progression was more substantial in the dorsal and basal regions in sb-group. this observation is supported by the fact that the progression of the lung collapse is stronger in the ventral areas than in the dorsal areas. since collapsed tissue is not expected to deform, it is the dorsal region the one expected to deform the most, which is confirmed by our regional strain analysis. these results suggest the deformation mechanisms associated with the contraction of the diaphragm are relevant to regional deformation. the caudal movement of the diaphragm is relative to its initial relationship with costal insertion, so the capacity to generate force in the caudal direction increases proportionally to the reduction of eelv, as in severe lung injury [ ] . these findings are in agreement with the experiment of yoshida and coworkers [ ] , where spontaneous breathing was beneficial in subjects with lung injury under mv when its severity was mild. the opposite effects occurred when the lung injury was severe, in which spontaneous breathing amplified the injury, thus increasing transpulmonary pressures, atelectasis, cyclic collapse, and histological signs of damage. similar to the findings of yoshida et al. in mechanically ventilated subjects with severe lung injury, we found more lung damage in sb-group. the paradox of spontaneous breathing and lung damage can be explained by the solid-like behavior of the injured lungs. contraction of the diaphragm generates non-uniform fluctuations of pleural pressure across the lung surface, producing an unsuspected overstretch in dependent regions and displacement of alveolar gas to non-dependent regions of the lungs (i.e., pendelluft) [ ] . in our study, the progression of non-aerated tissue in the sb-group may have intensified these phenomena, resulting in an imperfect elastic anisotropic inflation and amplifying the damage in the poorly aerated compartment of the lungs [ ] . another finding in our study was the progression of the heterogeneity of deformation of the lung, measured in terms of regional shi, in the sb-group. this observation suggests that sustained vigorous spontaneous ventilatory efforts might promote the progression of deformation heterogeneity in subjects with severe lung injury. in contrast, subjects on controlled mv showed fewer rois with progression of shi. inhomogeneity of ventilation has been proposed as a promoter of lung injury associated with ventilatory support. lung injury promoters are responsible for the amplification of damage injured lungs, even when mv parameters are within standard safety limits (non-harmful). the concept of stress raisers has been introduced to explain the amplification of damage in areas of high inhomogeneity [ , ] , linking the biological response in the lung parenchyma to the regional deformation in localized areas of the lung. the regional analysis showing inhomogeneity in the sb-group suggests that injurious patterns of ventilation in subjects without mv (spontaneous breathing), such as tidal recruitment, anisotropic inflation, and pendelluft phenomena, among others, can be associated with progression of injury, although the method we used cannot accurately characterize them. these findings take on particular translational relevance because regional differences in tissue aeration have been related to stress raisers and in patient mortality [ ] . it is important to note that regional stress is related to regional strain by means of constitutive relations (regional elastance); since regional strain can be directly estimated from image-based biomechanical analysis, it may serve as a better predictor of regional stress [ ] . it has been proposed that hyperventilation, due to vigorous diaphragm contraction, can amplify the lung injury. surprisingly, we did not find significant changes in v t in sb-group over time. with these observations, an important question arises: if strain increases in spontaneously breathing subjects, why v t does not change? several mechanisms might explain this conundrum. first, high respiratory drive progressively induces higher inspiratory flow over time. in the inhomogeneous lung, as sbgroup, fast alveolar units received more air, whereas the slow ones got deaerated, similar to other observations in subjects under mv [ , ] . also, high peak inspiratory flow in spontaneous breathing (deaccelerating pattern) increases the damage because the viscoelastic adaptation of the lung parenchyma does not have enough time to dissipate harmful forces [ ] . second, the hering-breuer reflex is a mechanism that can limit v t during spontaneous breathing in subjects with a high respiratory drive. third, vigorous breathing efforts in subjects with lung injury cannot be adjusted or regulated, even with appropriate sedation [ ] . a larger amplitude of the diaphragm caudal movement generates an excessive negative intrathoracic and interstitial pressure, contributing to venous return and formation of edema [ ] . concurrent with the progression of regional strain and heterogeneity, the sb-group displayed an increase in the non-aerated compartment and a reduction of the normally aerated compartment, which is associated with alveolar collapse. this result is in agreement with observations in subjects with acute lung injury breathing spontaneously under mv [ ] , and the ones described by mascheroni et al. in an experimental ovine study. the authors observed a severe deterioration of pulmonary function after . - h of pharmacologically induced hyperventilation in spontaneously breathing animals without lung disease. mv and pseudoparalysis prevented these alterations. this study confirms that vigorous spontaneous ventilation can affect the lung, and controlled mv can prevent or attenuate the damage of the lung in this setting [ ] . the development of hydrostatic lung edema in the sb-group might be a possible interpretation of these findings. in this group, a higher negative pleural pressure caused by more substantial spontaneous breathing efforts increases the transvascular alveolar pressure, which in turn results in augmented lung perfusion and finally, in edema [ ] [ ] [ ] [ ] [ ] . also, we need to consider that lung inflammation in regions exposed to high strain might lead to an increase in permeability; thus, they are more susceptible to edema. our work suffers from certain limitations that should be improved in future experiments. operational restrictions and scanning-time demand imposed by the micro-ct scanner did not allow for the use of invasive monitoring. it took over min for a full scan, and inside the scanning chamber, the spontaneous respiratory effort could not be monitored using esophageal pressure monitoring; monitoring gas exchange was also not possible. these restrictions prevented us from quantifying the parameters of global lung mechanics-oxygenation and ventilation-which are needed to classify the severity of the lung injury as well as the intensity of the respiratory effort. we note that subjects in the sb-group were also under anesthesia, which may modify the respiratory pattern. in addition, it is important to mention that our strain measurements in the mv-group are related to dynamic strain and do not account for the deformations that may occur due to the use of peep volume, which we believe are small compared to the dynamic strain. a technical limitation concerned with the image registration and biomechanical analysis is the fact that currently, the regional strain can only be computed in aerated regions of the lung. in particular, regional strain in the non-aerated areas was not calculated. this technical limitation does not allow us to conclude regarding the deformation of collapsed areas of the lung. despite these limitations, we highlight the unique character of this experimental design to study "patient self-inflicted lung injury" (p-sili). we measured the regional strain and heterogeneity in spontaneously breathing subjects in the whole lung. future studies should include a regional analysis of inflammation and atelectasis that could be spatially related to the different deformation measures proposed in this study to confirm correlations between regional deformation, tissue inflammation and edema, and their progression over time. spontaneous breathing can induce progression of lung injury by many mechanisms, a phenomenon known as p-sili. we identified a progression of regional deformation and heterogeneity in injured lungs under spontaneous breathing, but not in low v t mv subjects. this topic has profound implications in translational research, as patients with acute respiratory insufficiency can spontaneously breathe for extended periods before starting appropriate mv support, and also during unsuccessful weaning [ , ] . understanding the mechanisms involved in the progression of lung damage and its main determinants-heterogeneity and stress raisers, among others-will better support the decision to start or hold off mv support, thus balancing risks and benefits and potentially improving the clinical outcome. low v t mv is a strategy that can attenuate stress raising phenomena, thus reducing the maldistribution of regional strain dictated by lung heterogeneity [ ] . future studies need to assess whether other modalities of respiratory support, such as noninvasive mv and high-flow nasal cannulas, can attenuate the progression of lung injury and regional volumetric lung strain. lung stress and strain during mechanical ventilation: any safe threshold? does regional lung strain correlate with regional inflammation in acute respiratory distress syndrome during nonprotective ventilation? an experimental porcine study 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pressure at minimal respiratory elastance represents the best compromise between mechanical stress and lung aeration in oleic acid induced lung injury spontaneous breathing improves lung aeration in oleic acidinduced lung injury a scanographic assessment of pulmonary morphology in acute lung injury improving the accuracy of registration-based biomechanical analysis: a finite element approach to lung regional strain quantification spatial patterns and frequency distributions of regional deformation in the healthy human lung fast free-form deformation using graphics processing units registration-based lung mechanical analysis of chronic obstructive pulmonary disease (copd) using a supervised machine learning framework effect of local tidal lung strain on inflammation in normal and lipopolysaccharide-exposed sheep an asymptotic test for the equality of coefficients of variation from k populations actions of the respiratory muscles spontaneous effort causes occult pendelluft during mechanical ventilation stress distribution in lungs: a model of pulmonary elasticity the role of three-dimensionality and alveolar pressure in the distribution and amplification of alveolar stresses lung inhomogeneity in patients with acute respiratory distress syndrome ventilator-induced lung injury: the anatomical and physiological framework role of strain rate in the pathogenesis of ventilator-induced lung edema effects of inspiratory flow on lung stress, pendelluft, and ventilation heterogeneity in ards: a physiological study the future of mechanical ventilation: lessons from the present and the past spontaneous breathing: a double-edged sword to handle with care acute respiratory failure following pharmacologically induced hyperventilation: an experimental animal study esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives changes in transmural central venous pressure in man during hyperventilation exacerbation of acute pulmonary edema during assisted mechanical ventilation using a low-tidal volume, lung-protective ventilator strategy micromechanics of alveolar edema do spontaneous and mechanical breathing have similar effects on average transpulmonary and alveolar pressure? a clinical crossover study treatment of acute hypoxemic non-hypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial acute respiratory distress syndrome: predictors of noninvasive ventilation failure and intensive care unit mortality in clinical practice publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations authors acknowledge the financial support of the supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : figure s . schematic of the experimental protocol.additional file : figure s . schematic of the image acquisition process and image-based biomechanical analysis employed to construct threedimensional lung regional strain maps.additional file : table s . individual physiologic data for both groups. figure s . ct images of a representative subject in the sb-group showing the regional progression of lung collapse at the end of expiration (ee) and aeration at the end of inspiration (ei): (i) subject at t during ee, (ii) subject at t during ee, (iii) subject at t during ei, (iv) subject at t during ei.additional file : figure s . regional volumetric strain maps for representative subjects of the sb-group (top row) and the mv-group (bottom row) at t and t . progression of regional strain and heterogeneity in time is observed for the sb-subject, which reaches volumetric strain levels of up to %. regional strain distribution remains uniform and homogeneous in the mv subject. this work received funding from the consejo nacional de desarrollo científico y tecnológico conicyt chile through grants fondecyt regular , fondecyt regular , and fondef idea id i , and from the mille- key: cord- - nvhtqoh authors: pouly, olivier; lecailtel, sylvain; six, sophie; préau, sébastien; wallet, frédéric; nseir, saad; rouzé, anahita title: accuracy of ventilator-associated events for the diagnosis of ventilator-associated lower respiratory tract infections date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: nvhtqoh background: the aim of this study was to investigate the concordance between ventilator-associated events (vae) and ventilator-associated lower respiratory tract infections (va-lrti), and their impact on outcome. methods: this retrospective study was performed in five -bed icus of a teaching hospital, during a -year period. ventilator-associated lower respiratory tract infections (va-lrti), including ventilator-associated tracheobronchitis (vat) and ventilator-associated pneumonia (vap) were prospectively diagnosed. the agreement between vae, vat and vap was assessed by k statistics. results: a total of patients ( , ventilator-days) were included. vap ( . per ventilator-days), vat ( . per ventilator-days) and vae ( . per ventilator-days) were diagnosed. there was no agreement between vat and vae, and the agreement was poor between vap and vae (k = . , % ci . – . ). vae and va-lrti were associated with significantly longer duration of mechanical ventilation, icu and hospital length of stay. vap, vat and vae were not significantly associated with mortality in multivariate analysis. conclusions: the agreement was poor between vae and vap. no agreement was found between vae and vat. vae episodes were significantly associated with longer duration of mechanical ventilation and length of stay, but not with icu mortality. in spite of increased use of non-invasive mechanical ventilation, and high-flow nasal oxygen in the intensive care unit (icu), invasive mechanical ventilation is still used in a large proportion of critically ill patients [ ] . ventilator-associated lower respiratory tract infections (va-lrti), including ventilator-associated pneumonia (vap), and ventilator-associated tracheobronchitis (vat) are the most common complications in patients receiving mechanical ventilation. these infections are associated with increased duration of mechanical ventilation, length of hospital stay, and cost [ , ] . the diagnosis of these infections is based on chest x-ray, which is not specific in detecting new infiltrates in critically ill patients. therefore, the cdc recommended using a new definition for ventilator-associated events (vae), including infectious and other conditions. this definition includes only objective criteria and is perfectly reproducible [ ] . however, recent studies and meta-analysis reported poor agreement between vae, including ventilator-associated conditions (vac), infection-related ventilator-associated complications (ivac), or probable vap (pvap) [ ] [ ] [ ] . few studies evaluated the agreement between vae and va-lrti, including vap and vat. although vap and vat are both associated with increased duration of mechanical ventilation and length of icu stay, only vap is associated with increased mortality rates [ ] . thus, it is probably important to distinguish vap from vat. in addition, the recent ats/idsa guidelines on vap recommended not treating vat patients with antimicrobial, based on the low quality of the available evidence [ ] . therefore, we conducted this retrospective analysis of prospectively collected data to determine the agreement between vae and va-lrti, including vap and vat. we also aimed to determine the impact of vae on outcomes, including duration of mechanical ventilation, length of icu and hospital stay, and mortality. this study was conducted in five -bed icus in lille university hospital, during a -year period (from january st, through december st, ). the irb of the lille university hospital approved the study and waived informed consent. in accordance with the french law, and because of the retrospective observational design, written informed consent was not required. all patients hospitalized in one of the icus and receiving invasive mechanical ventilation for at least days were eligible for this study. patients who received mechanical ventilation for < days, and those who received mechanical ventilation for > h before icu admission were excluded. va-lrti included vap and vat. vap was defined as pneumonia diagnosed after h of intubation and mechanical ventilation. the diagnostic criteria for vap included a new infiltrate on chest x-ray associated with at least two of the following: body temperature ≥ . °c or < °c; leukocyte count ≥ × /l or < . × /l; and purulent tracheal aspirate or sputum. in addition, a microbiological confirmation was required for all patients (positive endotracheal aspirate culture ≥ colony-forming units (cfu)/ml or positive bronchoalveolar lavage culture ≥ cfu/ml) [ ] . vat was defined using the same criteria as for vap, except the presence of new or progressive pulmonary infiltrate. vae were diagnosed according to cdc definition (additional file : figure s ). vae diagnosis was considered concordant with that of vat or vap, when these infections occurred within days before or after the alteration of peep or fio (additional file : figure s ). a vap prevention strategy was routinely used during the study period. the ventilator circuit was not changed routinely. sedation and weaning were based on a written protocol. a minimal positive end expiratory pressure of cm h o was used in all patients. oral cavity was cleaned with chlorhexidine thrice daily. cuff pressure was measured and adjusted ( cm h o) by nurses thrice a day. tracheal suctioning was routinely performed by nurses, using an open tracheal suction system. patients remained in semi-recumbent position, and received enteral nutrition based on a written protocol. antibiotic treatment for patients with suspected vap was based on ats/idsa guidelines [ ] . antibiotic treatment for other infections was based on written local guidelines adapted from international and national guidelines. stress ulcer prophylaxis was not routinely used. selective digestive decontamination was not used. data related to vap and vat episodes were prospectively collected. data regarding mechanical ventilation (peep and fio ) were automatically imported every hour in the patient management software icip ® (philips healthcare). data from -h time slots were then retrospectively examined to determine the episodes of vae. other data such as body temperature, leukocytosis, antibiotic use, patient characteristics, aetiology of vae episodes, duration of mechanical ventilation and hospitalization, and mortality were collected retrospectively from patients' computerized medical records. the incidence rate and cohen's kappa coefficients were calculated on all episodes of vae, vap and vat. the concordance between the diagnosis for vac, ivac, pvap and that of vap and vat was determined by cohen's kappa statistic [ ] . only first episodes were taken to examine patients' characteristics according to the occurrence of vae, vap and vat. qualitative variables were expressed in percentage. because of non-normal distribution, quantitative variables were expressed in median, th and th percentiles. chi squared test, or fisher's exact test; and mann-whitney u test, or kruskal-wallis test, were used to compare the qualitative and quantitative variables, respectively. the difference was considered significant when p < . . when a significant difference existed between patients with vap, vat, and those with no va-lrti, comparisons between different groups were performed: vap vs vat, vap vs no va-lrti and vat vs no va-lrti. multivariate analyses, using forward multiple logistic regression models, were performed to determine the impact of va-lrti and vae on mortality, adjusting for age, saps ii and immunosuppression. out of the patients who received invasive mechanical ventilation, ( %) were excluded (fig. ). overall patients were included and received , days of invasive mechanical ventilation. a total of episodes of vac ( . for ventilatordays), vap ( . for ventilator-days) and vat ( . for ventilator-days) were diagnosed and used for concordance analysis. at least one episode of vac, ivac, and pvap was diagnosed in ( . %), ( . %), and ( . %) patients, respectively. at least one episode of vat or vap were diagnosed in ( . %) and ( . %) patients, respectively. among patients with vat, ( . %) patients developed a subsequent vap. a total of vat and vap were correlated with vac ( fig. ) . concordance (kappa statistic) between vac and vap, ivac and vap, pvap and vap were . ( % ci - . ), . ( % ci . - . ), and . ( ci . - . ), respectively ( table ) . because of the small number of patients with vae and vat (n = ), kappa statistic could not be calculated. the most common causes for vae were vap (n = , %), and atelectasis (n = , %). . % of vae were possibly related to vat, and no aetiology was found for ( , %) episodes (fig. ) . characteristics of patients who presented vat, vap, or no va-lrti are presented in table . a significant difference was found between the three groups regarding male gender, age, neurologic failure at icu admission, and immunosuppression. median duration of mechanical ventilation before vat, and vap occurrence was ( , ), and ( , ) days, respectively. the characteristics of patients with vac, ivac, or pvap, and those without these conditions are presented in table . in vac patients, as compared with those with no vac, male gender, sofa at icu admission, and bmi > were significantly higher. in ivac patients, as compared with those with no ivac, sofa score at icu admission, and bmi > were significantly higher. in pvap patients, as compared with those with no pvap, age, medical category, and charlson comorbidity index were significantly lower. median duration of mechanical ventilation before vac, and ivac, and pvap occurrence was ( , ) , ( , ) , and ( , ) days, respectively. icu mortality, duration of mechanical ventilation and length of stay were significantly different between patients with vap, vat, or no va-lrti (table ). in patients with vap, as compared with those with no va-lrti, duration of mechanical ventilation, and length of stay were significantly higher. in patients with vap, as compared with those with vat, icu mortality was significantly higher. in patients with vat, as compared with those with no va-lrti, duration of mechanical ventilation and length of stay were higher, and icu mortality was significantly lower. in multivariate analysis, the occurrence of va-lrti was not associated with mortality (table ) . although duration of mechanical ventilation and length of stay were significantly higher in patients with vac, ivac, or pvac, as compared with those without these conditions, no significant difference in mortality was found between these different groups ( table ). in multivariate analysis, the occurrence of vae, or of va-lrti was not associated with mortality (table ). our results suggest that vae are moderately correlated to vap, and not correlated to vat. vae and va-lrti are all associated with increased duration of mechanical ventilation and length of hospital and icu stay. va-lrti and vae were not independently associated with mortality. the strengths of our study include the large number of included patients (n = ) and ventilator days (n = , ), and the prospective evaluation of all va-lrti, including vat. previous studies reported similar findings regarding the correlation between vae and vap [ , , ] . however, few studies prospectively evaluated the incidence of vat in patients with vae [ , ] . among the diagnosed episodes of vae, only ( %) were possibly related to vat. thus, the correlation between vae, and vat could not be calculated. in a retrospective analysis of prospectively collected data, bouadma et al. [ ] identified aetiologies of each episode and found only % of vac caused by tracheobronchitis. worsening of ventilatory parameters is not a mandatory criterion for va-lrti definition, and only the clinical pulmonary infection score (cpis) includes the alteration of the pao /fio . our study and previous studies [ , ] reported that an important percentage of vae episodes were possibly related to vap, and not to vat. this clearly suggests that using alteration of oxygenation, i.e. pao /fio , could be helpful in differentiating vap from vat. differentiating these two infections could be a difficult task, as the accuracy of chest x-ray in diagnosing new infiltrates is low [ ] [ ] [ ] . however, it is still important to differentiate them, as antibiotic treatment is not recommended for vat and inappropriate use of antimicrobials is a risk factor for subsequent emergence of multidrug-resistant bacteria [ , ] . previous large observational studies and two small randomized controlled trials suggested beneficial effects of systemic and inhaled antibiotics. however, several limitations preclude definite conclusions on the interest of antimicrobials in patients with vat, and further large multicentre randomized controlled trials are required. the incidence of vae in our study is in line with previous findings. however, the incidence of vap ( %) is somehow higher than that reported by recent studies [ ] . this could be explained by the fact that only patients receiving mechanical ventilation for > days were included in our study. vae, and va-lrti were associated with significantly longer duration of mechanical ventilation and hospital and icu stay. however, vae and va-lrti were not independently associated with mortality. in contrast, two previous studies reported that vae were associated with significantly higher mortality rates [ , ] . vae diagnosis algorithm is based on objective criteria and easy to use in routine in mechanically ventilated patients. however, the clinical relevance of vae is not clear. first, our study and previous ones clearly showed that applying a vae algorithm surveillance is not accurate in detecting va-lrti. second, the impact of a ventilator bundle on vae incidence is unknown. few studies have focused on the preventability of vae, but it seems [ ] [ ] [ ] . our results show that many vae were non-infectious events as atelectasis, pleural effusion or acute pulmonary embolism. this might explain why ventilator bundles are not effective in preventing vae, and should not be used to assess the quality of care in mechanically ventilated patients. vae algorithm failed in identifying most of vat and % of vap episodes and should not be used to start an empirical treatment of va-lrti. furthermore, the retrospective nature of vae does not allow its use at bedside. in fact, to meet ivac criteria, patients must have days of stable oxygenation parameter and days of worsening ventilatory settings after which a new antibiotic must be prescribed for at least days. our study has some limitations. first, it was performed in a single center, and its results may not be generalized to all icu patients. second, it was retrospective. however, all va-lrti were prospectively identified. third, no data were collected on duration of antibiotic treatment before va-lrti, and vae, neither on appropriateness of antibiotic treatment in patients with va-lrti. fourth, the definition of vat and vap was based on chest x-ray that was interpreted by physicians in charge and no blind interpretation was performed. the prolonged duration of mechanical ventilation reported in patients with va-lrti, or vae, as compared to those with no infection, or no vae could not be attributed to these events as no adjustment was performed. vae and va-lrti are common in mechanically ventilated critically ill patients, and have a significant impact on duration of mechanical ventilation and length of stay. vae are moderately correlated to vap, and not correlated to vat. our results suggest that vae should not be used as a marker of quality of care or to start empirical antibiotic treatment. nosocomial infection surveillance in intensive care units clinical and economic consequences of ventilator-associated pneumonia: a systematic review incidence and prognosis of ventilator-associated tracheobronchitis (tavem): a multicentre, prospective, observational study assessment of an automated surveillance system for detection of initial ventilator-associated events does ventilator-associated event surveillance detect ventilator-associated pneumonia in intensive care units? a systematic review and meta-analysis electronic implementation of a novel surveillance paradigm for ventilator-associated events. feasibility and validation ventilator-associated pneumonia: present understanding and ongoing debates attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies management of adults with hospital-acquired and ventilatorassociated pneumonia: clinical practice guidelines by the infectious diseases society of america and the interrater reliability: the kappa statistic ventilator-associated events: prevalence, outcome, and relationship with ventilator-associated pneumonia the clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated assessing predictive accuracy for outcomes of ventilator-associated events in an international cohort: the euvae study the chest radiograph in critically ill surgical patients is inaccurate in predicting ventilator-associated pneumonia chest radiograph vs. computed tomography scan in the evaluation for pneumonia high discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ed patients: implications for diagnosing pneumonia international study of the prevalence and outcomes of infection in intensive care units understanding why resistant bacteria are associated with higher mortality in icu patients nosocomial pneumonia in icus in europe: perspectives from the eu-vap/cap study ventilator bundles in transition: from prevention of ventilatorassociated pneumonia to prevention of ventilator-associated events the preventability of ventilator-associated events. the cdc prevention epicenters wake up and breathe collaborative ventilator-associated events and their prevention publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . abbreviations ci: confidence interval; cpis: clinical pulmonary infection score; or: odds ratio; rgv: residual gastric volume; vap: ventilator-associated pneumonia; vat: ventilator-associated tracheobronchitis.authors' contribution sn, and ar designed the study. op, and sn performed statistical analyses. all authors collected the data, contributed in interpretation of the results, drafted and approved the submitted manuscript. sn had full access to the data and takes the responsibility for the integrity of the data and the accuracy of the data analysis. op and sl contributed equally to this study. all authors read and approved the final manuscript. none. all data are provided in the manuscript. the irb of the lille university hospital approved the study and waived informed consent. in accordance with the french law, and because of the retrospective observational design, written informed consent was not required. not applicable. sn: msd (advisory board and lecture); pfizer, gilead, bio rad, and biomérieux (lecture). ar: maatpharma (advisory board); pfizer (lecture). other authors: none. key: cord- -b ycocg authors: rutsaert, lynn; steinfort, nicky; van hunsel, tine; bomans, peter; naesens, reinout; mertes, helena; dits, hilde; van regenmortel, niels title: covid- -associated invasive pulmonary aspergillosis date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: b ycocg nan to the editor: since march , following in the footsteps of china, europe has been facing the covid- pandemic, caused by the sars-cov- virus [ ] . increasing numbers of patients are being admitted to intensive care units (icu) throughout the world, imposing multiple diagnostic and therapeutic challenges on stressed healthcare systems. in our -bedded mixed icu, we have encountered an unexpectedly high number of covid- patients developing invasive pulmonary aspergillosis. through our case series, we aim to raise awareness of this severe complication in the critical care community, point out different diagnostic obstacles and share our approach to the management of this complex problem. invasive pulmonary aspergillosis (ipa) is a well-known complication in immunocompromised patients and is encountered frequently in haematopoietic stem cell or solid organ transplant recipients [ ] . continued improvement in diagnostics has revealed that half of the cases of ipa occur in the icu, in patients who are often nonneutropenic [ , ] . severe influenza infection is a wellknown risk factor for developing ipa in non-neutropenic patients; a syndrome termed influenza-associated aspergillosis (iaa) [ ] [ ] [ ] . a damaged respiratory epithelium, dysfunctional mucociliary clearance and a local immune paralysis were demonstrated to be key pathophysiological factors [ ] . supported by the hypothesis that alveolar damage facilitates fungal invasion, acute respiratory distress syndrome (ards) has frequently been associated with ipa in the icu [ ] . with this in mind, the existence of covid- -associated pulmonary aspergillosis is deemed likely. between march th and april th , covid- patients were admitted to our icu, of whom ( %) required invasive mechanical ventilation. seven of these ventilated patients ( %) were suspected of ipa (table ) . median age in our patient cohort was (interquartile range - ) years. underlying comorbidities were primarily cardiovascular. only three patients were immunocompromised. one patient received chronic corticosteroid treatment for pemphigus foliaceous, one patient was hiv-positive (cd count > ; viral load < copies, treated with antiretrovirals [lamivudine/tenofovir/nevirapine]) and one patient had been treated for acute myeloid leukaemia years ago and had developed ipa during chemotherapy. all patients were intubated and mechanically ventilated due to severe covid- pneumonia. our suspicion was raised initially through an unusually rapid growth (< h) of aspergillus species in bronchial aspirates of three different patients. all samples were obtained during routine bronchoscopies, performed for atelectasis, respiratory deterioration or increasing inflammatory parameters. from that moment, routine galactomannan assays on serum and bronchoalveolar lavage (bal) fluid were assessed regularly and bronchoscopy-guided biopsies of suspicious tracheobronchial lesions were obtained whenever present. unfortunately, computed tomography (ct) scanning was deemed unfeasible in some patients due to extreme hypoxia or difficult mechanical ventilation and whenever performed, table shows the timing and results of the microbiological testing in our case series. differentiating between aspergillus colonization and ipa is notoriously difficult, especially in the icu. in the absence of host factors, as defined by the european organisation for research and treatment of cancer (eortc) diagnostic criteria, invasive or high-risk diagnostics (biopsy, ct scan) are required to support the diagnosis of ipa [ ] . the aspicu algorithm was designed to partially deal with the absence of host factors [ ] . based on this algorithm, four patients (no , , , ) were diagnosed with proven ipa, based on histopathological evidence. all of these patients showed positive galactomannan indices on bal fluid. in two patients, cultures and/or galactomannan bal only became positive post mortem (no , ), before ct scan or histopathological samples could be obtained. in one patient (no ), histopathological sampling was negative and galactomannan bal only mildly raised, but a raised serum galactomannan was later detected. in the remaining patients, the serum galactomannan index remained negative (< . ). the mean time between intubation date and the first microbiological signs of ipa was a striking (sd ) days. icu physicians often have to weigh the risks of further diagnostic tests against a delayed initiation of antifungal treatment, which is associated with mortality rates over % [ ] . because all patients with clinical features of possible ipa were suffering from severe respiratory failure and hemodynamic instability, we initiated antifungal therapy as soon as cultures or galactomannan assays were positive. five patients were started on voriconazole. in two of these patients, the treatment was escalated to isavuconazole due to pancytopenia or undetectable voriconazole levels under continuous renal replacement therapy. two patients died on treatment. to confirm and control this alarming incidence of covid- -associated ipa, a number of measures were taken. firstly, we ruled out an environmental source, by sampling room air and the oxygen and pressurized air supplies (mas , merck). prior to covid- , the incidence of ipa in our icu was not elevated. nonetheless, high-efficiency particulate air filters (hepa) (halton vita, helsinki, finland) were installed in the icu. secondly, all mechanically ventilated covid- patients were screened systematically by performing serum galactomannan assays twice weekly. whenever a bronchoscopy was needed, bal galactomannan indices and mould cultures were requested, regardless of the indication for bronchoscopy. finally, we initiated prophylactic nebulization of . mg of liposomal amphotericin b (ambisome ® , gilead, foster city, usa) in every mechanically ventilated patient without an established diagnosis of ipa [ ] . since the implementation of these measures, we have not encountered any new cases of ipa at the time of writing. using this case series, we would like to raise awareness about covid- -associated pulmonary aspergillosis, in view of its potential detrimental outcome. we believe that a low threshold for screening, prophylaxis and early antifungal treatment is of paramount importance, especially since different immunosuppressive therapies have been suggested to treat patients suffering from this alarming condition. sars-cov- infection among travelers returning from wuhan, china invasive pulmonary aspergillosis the clinical spectrum of pulmonary aspergillosis invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study invasive pulmonary aspergillosis complicating severe influenza: epidemiology, diagnosis and treatment diagnosing invasive pulmonary aspergillosis in icu patients: putting the puzzle together revised definitions of invasive fungal disease from the european organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (eortc/msg) consensus group inhaled amphotericin b as aspergillosis prophylaxis in hematologic disease: an update. microbiol insights publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we want to thank our entire icu team for their unwavering commitment during these challenging times. lr wrote the first draft of manuscript with input and revisions from nvr and ns. ns collected the data from the source documents. tvh and lr performed the literature search. pb and hd advised on the reporting of the clinical data; rn and hm on the reporting of the microbiological and infection prevention data. all authors had full access to all of the data. all authors read and approved the final manuscript. none. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. publication approval granted by the ethics committee. not applicable. the authors declare that they have no competing interests. key: cord- - kw v rm authors: vuillard, constance; pineton de chambrun, marc; de prost, nicolas; guérin, claude; schmidt, matthieu; dargent, auguste; quenot, jean-pierre; préau, sébastien; ledoux, geoffrey; neuville, mathilde; voiriot, guillaume; fartoukh, muriel; coudroy, rémi; dumas, guillaume; maury, eric; terzi, nicolas; tandjaoui-lambiotte, yacine; schneider, francis; grall, maximilien; guérot, emmanuel; larcher, romaric; ricome, sylvie; le mao, raphaël; colin, gwenhaël; guitton, christophe; zafrani, lara; morawiec, elise; dubert, marie; pajot, olivier; mentec, hervé; plantefève, gaëtan; contou, damien title: clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-mda- dermato-pulmonary syndrome: a french multicenter retrospective study date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: kw v rm background: anti-synthetase (as) and dermato-pulmonary associated with anti-mda- antibodies (amda- ) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease. we undertook a -year retrospective multicenter study in french icus in order to describe the clinical presentation and the outcome of patients admitted to the icu for acute respiratory failure (arf) revealing as or amda- syndromes. results: from to , patients ( males; median age [ st– rd quartiles – ] years, no comorbidity %) were admitted to the icu for arf revealing as (n = , %) or amda- (n = , %) syndromes. muscular, articular and cutaneous manifestations occurred in patients ( %), ( %) and ( %) patients, respectively. seventeen of them ( %) had no extra-pulmonary manifestations. c-reactive protein was increased ( [ – ] mg/l), whereas procalcitonine was not ( . [ . – . ] ng/ml). proportion of patients with creatine kinase ≥ n was % (n = / ). forty-two patients ( %) had ards, which was severe in %, with a rate of % (n = / ) of extra-corporeal membrane oxygenation requirement. proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were %, %, %, % and %, respectively. icu and hospital mortality rates were % (n = / ) and % (n = / ), respectively. patients with amda- dermato-pulmonary syndrome had a higher hospital mortality than those with as syndrome (n = / , % vs. n = / , %; p = . ). conclusions: intensivists should consider inflammatory myopathies as a cause of arf of unknown origin. extra-pulmonary manifestations are commonly lacking. mortality is high, especially in amda- dermato-pulmonary syndrome. identifying the cause of acute respiratory distress syndrome (ards) is a crucial step for initiating a targeted treatment and improving prognosis [ , ] . however, two recent studies [ , ] showed that % of patients with ards according to the berlin criteria [ ] lacked exposure to "common" risk factors (e.g., pneumonia, acute pancreatitis, aspiration of gastric content or extra-pulmonary sepsis) with no etiology eventually retrieved in % of them [ ] . for such atypical ards, a comprehensive diagnostic work-up, including specific immunologic tests, is recommended [ ] so that to identify immune causes, typically amenable to specific therapeutic interventions (e.g., corticosteroids). yet, an ancillary analysis [ ] of an international, multicenter, prospective cohort study [ ] reported that such immunological examinations were performed in only % of ards without common risk factors. anti-synthetase (as) and anti-melanoma differentiation-associated gene (amda- ) syndromes are near one of the other autoimmune inflammatory myopathies [ ] potentially responsible for rapidly progressive interstitial lung disease leading to acute respiratory failure and ards [ ] [ ] [ ] [ ] . as and amda- dermatopulmonary syndromes may be clinically indistinguishable one from another, with almost three-quarter of patients with amda- dermato-pulmonary syndrome exhibiting the clinical attributes of the as syndrome [ ] . when arf is the initial presentation of as or amda- syndromes [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] or when extra-respiratory manifestations, such as muscular, cutaneous or articular signs are lacking [ , [ ] [ ] [ ] [ ] [ ] , the diagnosis is challenging, especially in the intensive care unit (icu) setting, where many other reasons of acute respiratory failure (arf) can be discussed. to the best of knowledge, a number of case reports of arf revealing autoimmune inflammatory myopathies have been previously reported, but an extended case series has not been published as yet. therefore, we undertook this retrospective study in order to: ( ) describe the clinical features and the outcome of patients admitted to the icu for arf revealing either an as or an amda- dermato-pulmonary syndrome, and; ( ) identify predictive factors of hospital mortality. we conducted a -year multicenter retrospective noninterventional study in icus in france from january , , to december , . all patients older than years were included if they met the following criteria: ( ) admitted to the icu for arf not related to cardiogenic pulmonary edema; ( ) no common ards risk factor, among pneumonia, acute pancreatitis, aspiration of gastric content, extra-pulmonary sepsis, multiple transfusions, major trauma, pulmonary vasculitis, drowning, severe burns, identified according to the berlin definition [ ] ; ( ) immunologic test performed during icu stay, which was positive for anti-synthetase (jo- , pl , pl , oj, ej, ks, zo, yrs/tyr/ha) or anti-mda- autoantibodies; and ( ) no alternative diagnosis for arf. it is worth notifying that in the present study the diagnosis of as or amda- dermato-pulmonary syndromes had to be made during the icu stay. therefore, those who had a diagnosis of as or amda- made before icu admission were not included. the investigator of each participating center was responsible for the identification of the patients, either from the hospital medical reports, using the function "research the files in which the key words mda- or antisynthetase or myositis occurs" of microsoft windows ® , or through a search using the international classification of diseases ( th revision) following codes: m (autoimmune myositis), m (myositis), m (polymyositis) and m (dermatomyositis). the clinical charts of all identified patients were anonymized before sending to the main investigators (dc and cv). clinical charts were reviewed in order to check the inclusion criteria. the following data were collected on a standardized anonymized case record form: demographic characteristics (age, gender), severity scores upon icu admission (sequential organ failure assessment [ ] and simplified acute physiology score ii [ ] ), main comorbidities, delay between first respiratory sign and icu admission, clinical examination (respiratory and extra-respiratory manifestations) and laboratory findings at the time of icu admission (blood leukocytes and platelets counts, serum procalcitonine, c-reactive protein, creatine kinase and creatinine levels, pao /fio with fio calculated according to the following formula [ , ] : fio = oxygen flow in liter per minute × . + . when standard oxygen was used), radiological findings on chest x-ray and ct scan, cytological and bacteriological analyses of broncho-alveolar lavage (bal) fluid, type of positive autoantibodies (jo- , pl , pl , oj, ej, ks, zo, yrs/tyr/ ha or amda- ), immunosuppressive treatments received (corticosteroids, cyclophosphamide, rituximab, basiliximab, tacrolimus, cyclosporine, methotrexate, intravenous immunoglobulins or plasma exchange), organ supports in the icu (invasive mechanical ventilation, extra-corporeal membrane oxygenation (ecmo), renal replacement therapy, vasopressors), icu and hospital length of stay, icu and hospital mortality. written reports of chest ct scan performed at the time of icu admission were sent to the main investigators (dc and cv) in order to individualize elementary lesions (ground-glass attenuation, alveolar consolidation, septal thickening, pleural effusion, pneumothorax, pneumomediastinum and mediastinal lymphadenopathy) and their location (lower or upper lobe predominance). signs of lung fibrosis (honeycombing, traction bronchiectasis and reticulations) were also collected. cytological analyses of bal fluid collected at the time of icu admission were reported, as well as results of open lung, skin or muscle biopsies, if performed. continuous variables are reported as median [ st- rd quartiles] and compared by the mann-whitney u test. categorical variables are reported as counts and percentage points in groups and compared by using the fisher's exact test. survival curves of patients with amda- and as syndromes were drawn using the kaplan-meier method and compared using the log-rank test. all tests were two-sided, with p < . indicating statistical significance. the statistical analysis was performed by using the rstudio software version . . (www.rstud io.com). from january , , to december , , patients fulfilled the inclusion criteria, including ( %) with as syndrome (jo- n = / ( %); pl n = / ( %); pl n = / ( %); ej n = / ( %)) and ( %) with amda- dermato-pulmonary syndrome. all the patients with amda- dermato-pulmonary syndrome were admitted after january , . demographical characteristics, main comorbidities and clinical manifestations are given in table . most of the patients had no comorbidity (n = / , %). median sapsii and sofa scores at the time of icu admission were and [ ] [ ] [ ] [ ] [ ] [ ] , respectively. the median delay between first respiratory sign and icu admission was days. most of the patients had central temperature > °c (n = / , %). myalgia, arthralgia/arthritis and cutaneous manifestations occurred in % (n = / ), % (n = / ) and % (n = / ) of patients, respectively. about one-third of patients (n = / , %) had no extra-pulmonary manifestation, in a similar proportion in amda- and as groups. biological data at the time of icu admission and radiological findings are reported in table . c-reactive protein levels (n < mg/l) were increased ( mg/l), while procalcitonine levels (n < . ng/ml) were not ( . [ . - . ] ng/ml). the rate of patients having creatine kinase plasma levels greater than times the upper limit of normal laboratory range was % (n = / ) in the whole population, and only % (n = / ) in the as group. the median pao /fio ratio at icu admission was [ - ] mmhg. most patients (n = / , %) had bilateral condensations on chest x-ray, with a predominantly lower location (n = / , %) ( table ). all patients underwent a lung ct scan, which showed ground-glass attenuation in % (n = / ) and alveolar condensation in % (n = / ). signs of lung fibrosis were observed in % (n = / ), while % (n = / ) had mediastinal lymphadenopathies. bal fluid analyses were available in % (n = / ) of patients and are summarized in table . the cell count was [ - ] × /ml, and percentages of lymphocytes, neutrophils and macrophages were % , % and % , respectively. bal was performed before antibiotic therapy in only / ( %) patients and was negative for lung infection in every patient. there was no correlation between bal findings and elementary lesions observed on chest ct scan. in particular, the proportion of patients with > % bal neutrophils did not differ between patients with or without elementary lesions of lung fibrosis on chest ct scan (n = / , % vs. n = / , %, p = . ). an open lung biopsy was performed in ( %) patients and depicted findings consistent with organizing pneumonia (n = ), usual interstitial pneumonitis (n = ) and diffuse alveolar damage (n = ) ( table ). a total of patients ( %) had a muscle (n = ) or a skin (n = ) biopsy performed during the icu stay. all muscle biopsies revealed findings consistent with an inflammatory myositis, while skin biopsies were either normal (n = ) or revealed findings consistent with lichenoid dermatitis (n = ) or with dermatomyositis (n = ) ( table ) . most patients (n = / , %) received an antimicrobial therapy upon icu admission (table ). all patients received steroids, after a median delay of [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days following the icu admission. other immunosuppressive treatments administered are reported in table . almost all patients (n = / , %) had ards, categorized as severe (pao /fio ≤ mmhg with peep ≥ mmh o) in % (n = / ), with % (n = / ) of them requiring ecmo. icu and hospital mortality rates were % (n = / ) and % (n = / ), respectively. patients with amda- dermato-pulmonary syndrome had a higher icu mortality than those with as syndrome (n = / , % vs. n = / , %; p < . ). among the icu survivors, ( %) were diagnosed with a cancer (colorectal n = , pharyngeal n = , melanoma n = ) during the [ - ] days post-icu stay follow-up. compared to patients who survived at the hospital discharge, those who died were more likely to have an amda- autoantibody (n = / , % vs. n = / , %; p = . ), had a higher rate of ground-glass attenuation table demographical and clinical manifestations of patients with acute respiratory failure revealing anti-synthetase syndrome or dermato-pulmonary syndrome associated with anti-mda- antibodies amda- anti-mda- antibodies, as anti-synthetase, arf acute respiratory failure, hiv human immunodeficiency virus, icu intensive care unit, iqr inter-quartile range, saps simplified acute physiology score, sofa sepsis-related organ failure assessment chronic respiratory failure ( ) ( ) ( ) . congestive heart failure ( ) ( ) ( ) . chronic kidney failure active solid cancer or malignant hemopathy ( ) ( ) ( ) . table ). after adjustment on syndrome (anti-synthetase or amda- dermato-pulmonary syndrome), the presence of ground-glass attenuations on chest ct scan was no longer associated with in-hospital mortality (p = . ). the kaplan-meier graph showed a lower probability of survival days after icu admission in patients with amda- antibody than in patients with as antibody (fig. ; p < . log-rank test). we are herein reporting the first large cohort of patients admitted to icu for arf revealing either as or amda- dermato-pulmonary syndrome. the main findings are: ( ) clinical manifestations may be nonspecific with the absence of extra-pulmonary manifestations of inflammatory myositis in one-third of patients; ( ) hypoxemia is severe with a high rate of severe ards and rescue maneuvers; and ( ) hospital mortality is high, especially in dermato-pulmonary syndrome associated with amda- autoantibodies. as and amda- -associated dermato-pulmonary syndromes are two near each of the other inflammatory myopathies that may be responsible for severe acute interstitial lung diseases [ ] [ ] [ ] . the diagnosis is easy to consider when extra-pulmonary manifestations are present. in as syndrome, the main extra-pulmonary manifestations include myositis with elevated creatine kinase levels, non-erosive arthritis, raynaud's phenomenon and thick cracked skin over the tips and sides of the fingers called "mechanic's hands" [ ] [ ] [ ] [ ] [ ] [ ] . however, there is a wide heterogeneity in clinical manifestations depending on the causative as autoantibody [ , ] . in amda- -associated dermato-pulmonary syndrome, the cutaneous manifestations (skin ulcerations or necrosis, facial erythema, mechanic's hands, periungual telangiectasia, gottron's papules, raynaud's phenomenon) are in the forefront [ , , ] and usually contrast with the absence of clinical signs of myositis (clinically "amyopathic myositis"). demographical and clinical findings in our patients were in line with those recently reported in non-icu patients with as [ , , ] or with amda- dermato-pulmonary syndromes [ ] . both in as and amda- dermato-pulmonary syndromes, extra-pulmonary manifestations may be lacking [ , ] rendering the diagnosis difficult to make. in our series, more than one-third of patients had no extra-pulmonary manifestations with a similar proportion in as and amda- patients. this rate contrasts with the % rate recently reported [ ] in patients with amda- dermato-pulmonary syndrome, reflecting the lack of training of intensivists for the clinical assessment of these patients and highlighting the need for a multidisciplinary approach. considering the high proportion of patients lacking extra-pulmonary manifestations, the clinical presentation may mimic that of a "bilateral pneumonia without microbiological documentation. " hence, % of our patients received antibiotic therapy at icu admission. the presence of an intense inflammatory syndrome with increased c-reactive protein levels contrasting with the lack of elevation of serum procalcitonine could help intensivists appreciating the probability of an infectious process, this dissociation being highly suggestive of a non-infectious inflammatory process. in our series, bal was performed in % of patients. unlike a recent work [ ] showing that a lymphocytic bal fluid was associated with better icu survival in ards patients with no common risk factor, our study failed to identify any predictive role of bal cytology on hospital survival. bal fluid analysis does not seem a useful diagnostic tool for as or amda- dermato-pulmonary syndromes, but should nevertheless be performed to rule out an alternative diagnosis, such as diffuse alveolar hemorrhage or active infection. all included patients underwent chest ct scan. interestingly, ct chest findings predominate in the lower lobes, which is consistent with a previous report [ ] . ct scan signs of lung fibrosis have been recently shown to be associated with a poor outcome in patients with arf related to interstitial lung diseases [ ] . in our study, ct scan signs of lung fibrosis were not associated with hospital mortality, probably because of a lack of adequate power. while ground-glass opacities are usually considered as potentially reversible lung lesions during idiopathic pulmonary fibrosis [ , ] , these lesions were associated with in-hospital mortality in our study, probably because they were more frequently observed during amda- dermato-pulmonary syndromes. indeed, this association was no longer observed after adjustment on the type of positive antibody (anti-synthetase or amda- ). our series underlines the severity of as and amda- dermato-pulmonary syndrome, since % of patients fulfilled the berlin criteria for ards [ ] , categorized as severe (pao /fio ≤ mmhg with peep ≥ mmh o) in % of cases. anti-mda- dermato-pulmonary syndromes exhibited a significantly higher mortality than as syndromes, with almost all these patients dying in the icu of refractory ards despite a high rate of ecmo ( %). moreover, amda- patients had a much higher mortality than those with severe ards included in the lung safe study [ ] , highlighting the irreversibility of lung lesions despite immunosuppressive treatments. these results are in line with previous series, showing that refractory ards is the leading cause of mortality in amda- patients [ ] . whether our patients had a true ards (i.e., presence of diffuse alveolar damage (dad), the histological hallmark of ards) or simply fulfilled the berlin criteria while having a non-dad histology is unknown. in fact, the berlin definition of ards is not fully reliable for diagnosing dad, and several non-dad histological entities (such as lung fibrosis, organizing pneumonia, diffuse alveolar hemorrhage or lung tumoral infiltration) have been reported in patients fulfilling the clinical and radiological criteria for ards [ , [ ] [ ] [ ] . regarding the onset of lung injury, the berlin definition of ards stipulates that "respiratory signs should occur (or worsen) within days after an exposure to a common ards risk factor" (e.g., pneumonia, acute pancreatitis, aspiration of gastric content or extra-pulmonary sepsis). in our patients, the absence of a common risk factor for ards according to the berlin definition together with delay between first respiratory sign and icu admission exceeding days ( days) advocate more for an ards mimicker rather than for a real ards. however, a recent histological study revealed that % of patients with an acute decompensation of as syndrome due to jo- autoantibody exhibited histological lesions of dad [ ] . in non-icu patients, the prognosis of inflammatory myopathies depends on the severity of lung involvement [ , , , ] . treatment of interstitial lung disease associated with as and amda- dermato-pulmonary syndromes is not standardized and based on case reports. numerous immunosuppressive therapies are available (e.g., cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, rituximab, basiliximab, intravenous immunoglobulins or plasma exchange) [ , , , , , ] , but high-dose corticosteroids remain the first-line therapy. our study underlines the wide variations in the choice of immunosuppressive treatment even if the association corticosteroids-cyclophosphamide was administered in almost over patients. patients with amda- received significantly more immunosuppressive drugs highlighting a higher severity. of note, % of icu survivors developed cancer, in line with previous series of as patients [ ] . our study suffers from several limitations. first, we included a limited number of patients, inherent to the rarity of the disease. however, this is the first series on arf revealing as or amda- syndromes in an icu context and our findings are consistent with previous reports. this limited number of patients precluded performing multivariable analyses and thus did not allow for adjusting the observed association between some variables and mortality with potential confounders. second, the relationship between positive as or amda- autoantibody and arf is not proven. we therefore cannot exclude that some patients had a fortuitously positive autoantibody and that inflammatory myopathy was not the cause of arf. however, this hypothesis appears unlikely since an alternative diagnosis for arf had to be excluded, and all patients were treated with immunosuppressive therapies underlining the high degree of clinician's suspicion. third, because the patients were recruited over a -year period in centers, icu procedures were inevitably heterogeneous. fourth, the prevalence of amda- dermato-pulmonary syndromes may have been underestimated during the study period since detection of amda- autoantibody was first described in [ ] and was therefore routinely available only from in most of participating centers. last, several classical predictors of mortality related to ventilation (tidal volume or driving pressure [ ] ) were not available as a result of a long-term retrospective design. considering the high proportion of patients lacking extra-pulmonary manifestations and the nonspecific presentation mimicking that of a bilateral communityacquired pneumonia, we believe that arf related to autoimmune inflammatory myopathies may be underdiagnosed. hence, de prost et al. recently showed that the diagnostic work-up performed in ards patients with no common risk factor was not comprehensive, with only % of patients having immunological tests [ ] . the lack of screening for as or amda- autoantibodies is probably one of the reasons why these diseases are underestimated. therefore, when the etiology of arf appears unclear, we recommend a more aggressive diagnostic work-up [ ] , including immunological tests in order to identify patients amenable to specific therapies. a careful assessment of extra-pulmonary manifestations, such as cutaneous or articular signs, is crucial. while the presence of extra-pulmonary manifestations is highly suggestive, the -week delay between first respiratory signs and icu admission, the absence of an obvious etiology for arf, the presence of bi-basal consolidations on chest x-ray with an intense inflammatory process, contrasting with a low procalcitonin level together with the lack of microbiological documentation are the main clues to consider the diagnosis of as or amda- syndromes in a patient without extra-pulmonary manifestation. to better assess the relevance of these signs, further prospective studies aiming at systematically screen for autoantibodies in ards without risk factors are needed. once the diagnosis is made, the management is difficult and requires a multidisciplinary approach involving intensivists, pulmonologists, internists and rheumatologists in order to decide the best-individualized therapeutic strategy. intensivists should consider inflammatory myopathies, such as anti-synthetase syndrome and dermato-pulmonary syndrome associated with anti-mda- antibodies, as a cause of acute respiratory failure when the etiology appears unclear. extra-pulmonary manifestations are commonly lacking and an isolated lung involvement may reveal the disease. hospital mortality is high, especially in amda- dermato-pulmonary syndrome. abbreviations ards: acute respiratory distress syndrome; arf: acute respiratory failure; as: anti-synthetase; amda- : anti-mda- autoantibody; bal: broncho-alveolar lavage; dad: diffuse alveolar damage; ecmo: extra-corporeal membrane oxygenation; icu: intensive care unit. dc had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. dc made substantial contribution to the study design, data collection and analysis and manuscript writing. cv contributed to data collection and interpretation, and drafting of the manuscript. mpc, ndp, ad, j-pq, sp, gl, mn, gv, mf, rc, gd, em, nt, yt-l, fs, mg, eg, rl, sr, rlm, gc, cg, lz and em contributed to patients identification in each center, data collection and manuscript writing. md contributed to the data analysis, statistical analysis and manuscript revision. ndp, cg, op, hm and gp contributed to the manuscript writing and revision, and provided important intellectual content. all authors read and approved the final manuscript. service de réanimation, centre hospitalier universitaire de grenoble alpes, avenue maquis du grésivaudan, la tronche, france. service de réanimation médico-chirurgicale, centre hospitalier universitaire avicennes -assistance publique hôpitaux de paris, rue de stalingrad, bobigny, france. service de réanimation service de réanimation médico-chirurgicale service de réanimation médico-chirurgicale, centre hospitalier du mans, avenue rubillard, le mans, 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syndrome the authors declare that they have no competing interests. the study was approved by institutional review board of the french society for respiratory medicine in september (cepro - ), which waived informed consent. this study did not receive funding from external or internal sources. key: cord- -b wm db authors: gaborit, benjamin jean; tessoulin, benoit; lavergne, rose-anne; morio, florent; sagan, christine; canet, emmanuel; lecomte, raphael; leturnier, paul; deschanvres, colin; khatchatourian, lydie; asseray, nathalie; garret, charlotte; vourch, michael; marest, delphine; raffi, françois; boutoille, david; reignier, jean title: outcome and prognostic factors of pneumocystis jirovecii pneumonia in immunocompromised adults: a prospective observational study date: - - journal: ann intensive care doi: . /s - - -x sha: doc_id: cord_uid: b wm db background: pneumocystis jirovecii pneumonia (pjp) remains a severe disease associated with high rates of invasive mechanical ventilation (mv) and mortality. the objectives of this study were to assess early risk factors for severe pjp and -day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis. methods: we prospectively enrolled all patients meeting pre-defined diagnostic criteria for pjp admitted at nantes university hospital, france, from january to january . diagnostic criteria for pjp were typical clinical features with microbiological confirmation of p. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (pcr) assay. severe pjp was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least % fio( ), non-invasive ventilation, or mv. results: of respiratory samples investigated during the study period, from patients were positive for p. jirovecii. of these patients, met criteria for pjp and were included in the study, ( . %) patients had severe pjp, including who required mv. all patients were immunocompromised with haematological malignancy ranking first (n = , %), followed by solid organ transplantation (n = , %), hiv-infection (n = , %), systemic diseases (n = , %), solid tumors (n = , %) and primary immunodeficiency (n = , %). by multivariate analysis, factors independently associated with severity were older age (or, . ; % ci . – . ; p < . ), a p. jirovecii microscopy-positive result from bronchoalveolar lavage (bal) (or, . ; % ci . – . ; p < . ); and absence of a bal fluid alveolitis profile (or, . ; % ci . – . ; p < . ). the -day mortality rate was %, increasing to % in the severe pjp group. factors independently associated with -day mortality were worse sofa score on day (or, . ; % ci . – . ; p < . ) whereas alveolitis at bal was protective (or, . ; % ci . – . ; p < . ). in the subgroup of hiv-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher -day mortality (or, . ; % ci . – . ; p < . ). conclusions: older age and p. jirovecii oocysts at microscopic examination of bal were independently associated with severe pjp. both initial pjp severity as evaluated by the sofa score and viral co-infection predicted -day mortality. alveolitis at bal examination was associated with less severe pjp. the pathophysiological mechanism underlying this observation deserves further investigation. over the last years, survival benefits provided by steady advances in antitumor chemotherapy and immunosuppressant regimens for patients with autoimmune diseases, haematological malignancies, and solid organ transplants have substantially increased the number of adults living with immunodeficiencies [ , ] . among opportunistic infections in immunocompromised adults, pneumocystis jirovecii pneumonia (pjp) was associated with high rates of intubation and mortality [ ] . consequently, an early identification and optimal treatment of patients with pjp remains a key priority [ , ] . since the advent of antiretroviral therapy, the incidence and mortality rates of pjp among patients positive for the human immunodeficiency virus (hiv) have decreased steadily [ ] . however, pjp is being increasingly diagnosed in hiv-negative patients, in whom it carries a poorer prognosis [ , ] . a higher proportion of neutrophils in broncho-alveolar lavage (bal) fluid during pjp was associated with higher risks of respiratory complications and mortality [ , ] . in the same way, a low lymphocyte count in bal fluid was a risk factor for the failure of trimethoprim/sulfamethoxazole (tmp/smz) therapy [ ] . early adjunctive steroid therapy for severe pjp dramatically decreased mortality rates in hiv-positive patients [ , ] but had variable effects in their hivnegative counterparts [ ] [ ] [ ] . these findings suggest that the immunological status and underlying diagnosis may influence the pathophysiology of pjp and the risk of mortality [ , ] . however, bal fluid cytology profiles have not been adequately evaluated as potential prognostic factor and predictors of treatment responses. the identification of early predictors of pjp outcomes, including bal fluid findings, may help to determine which patients are most likely to benefit from intensive care and could justify adjunctive steroid therapy. the aim of this prospective study of patients with pjp was to identify early risk factors for severe pjp and -day mortality. this is a retrospective analysis of prospective cohort. from january to january , all patients presenting an invasive fungal infection that has been diagnosed in our center have been included in a prospective registry (the french prospective surveillance programme, ressif network), thus pjp patients have been included in a subcohort. for each patient with a positive sample, the following clinical findings were prospectively investigated: dyspnea and/or cough in immunocompromised patients with interstitial syndrome by radiography or ct scan. among all respiratory samples investigated for years (n = ), all positive tests for pneumocystis jirovecii samples (n = ) were assessed by a biologist and a clinician to investigate criteria for pjp and include them in this prospective cohort. the following data were prospectively collected: age; sex; underlying disease; pjp prophylaxis; other medications including glucocorticoids taken during the past month; type of symptoms and symptom duration at pjp diagnosis and time from symptom onset to hospital admission. secondary, the clinical data were collected for all patients from medical records: laboratory findings (white blood cell count; absolute neutrophil count; c-reactive protein [crp] level; bal fluid findings including the cell profile assessed by an independent cytologist on centrifuged bal fluid samples prepared with the wright-giemsa and perls stains to allow the determination of macrophage, lymphocyte, neutrophil, eosinophil, and basophil counts); presence of p. jirovecii and/or other fungi and/or bacteria and/or viruses (influenza viruses, respiratory syncytial virus, adenovirus, cytomegalovirus) were recorded at pjp diagnosis. the sofa score on day and the ratio of the arterial partial pressure of oxygen over the fraction of inspired oxygen (pao /fio ) on day [ ] were recorded for each patient at pjp diagnosis. anti-pjp medications, adjuvant glucocorticoid therapy, oxygen supplementation, and ventilatory support provided at admission were documented. finally, patient outcomes including -day mortality were recorded. the collection of follow-up data ended in december . severe pjp was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least % fio , non-invasive ventilation, or mv. because not all patients were hospitalized in intensive care units, we chose this pragmatic and reproducible severity criterion. according to the berlin definition [ ] , severe acute respiratory distress syndrome (ards) was defined as the presence of the following criteria within days after icu admission: new respiratory symptoms, bilateral opacities mortality. alveolitis at bal examination was associated with less severe pjp. the pathophysiological mechanism underlying this observation deserves further investigation. keywords: pneumocystis jirovecii pneumonia, early prognostic score, high flow oxygen, haematological malignancies, alveolitis on chest radiographs or by ct, absence of suspected hydrostatic/cardiogenic pulmonary oedema, and pao / fio ≤ . lymphocytic alveolitis [ ] was defined as a bal fluid cell population containing more than % of lymphocytes and more than % of neutrophils combined with an activated macrophage phenotype, based on the diagnostic criteria for hypersensitivity pneumonitis, a condition characterised by alveolitis and migration to the alveoli of multiple cell types including activated t cells, monocytes, and natural killer cells [ ] . finally, patients with other pathogens associated with p. jirovecii in respiratory or blood samples were classified as having coinfection at icu admission. patient characteristics were described using mean ± sd for continuous variables (or % confidence interval [ % ci] when appropriate) and proportions for qualitative variables. continuous variables were compared using the wilcoxon rank-sum and kruskal-wallis tests and qualitative variables using fisher's exact test with computation of the odds ratios (ors) and their % cis. overall survival was assessed using kaplan-meier curves and log-rank tests. factors associated with severity were identified by logistic regression analysis. factors associated with all-cause -day mortality were identified by logistic regression analysis of patients alive after day versus patients who died before day . only factors reaching statistical significance (p < . ), with no more than % missing data, were included in the multivariate model. when collinearity between co-variates was detected, only the variable with the highest or was kept into the multivariate regression model. results are reported as log-transformed coefficients with their % cis. missing data were not interpolated. analyses were performed on the whole population, then excluding hiv+ patients. of the respiratory samples tested during the study period, from patients were positive for p. jirovecii. of these patients, met our pjp criteria and were included in the study; table reports their main characteristics. the remaining patients were classified as having bronchial p. jirovecii colonisation (fig. ). the mean number of patients included per year was and the number of patients per year increased gradually over time to reach a peak of patients in (additional file : figure s ). of the patients with pjp, had positive bal fluid, by a direct examination of bal fluid in patients and only detected by pcr in patients. the induced sputum test was positive in patients (by pcr, n = ; time from onset to bal, days, mean ± sd ± . pj visible in smears, n (%) ( . ) alveolitis profile, n (%) ( ) co-infection at pjp diagnosis, n (%) viral infection ( ) bacterial infection ( ) invasive fungal infection ( ) and/or grocott-gomori stain, n = ). both the bal fluid and the induced sputum test were positive in patients. all patients were immunocompromised with haematological malignancy ranking first (n = , %), followed by solid organ transplantation (n = , %), hiv-infection (n = , %), systemic diseases (n = , %), solid tumors (n = , %) and primary immunodeficiency (n = , %). the mean hiv viral load at pjp diagnosis was , copies for hiv-positive patient. only ( . %) patients were given pjp prophylaxis. of these, were compliant with the prescription during the last months before diagnosis, which never consisted in tmp/smz. the first-line pjp therapy was tmp/smz for ( . %) patients, ( . %) patients being treated with atovaquone; no pjp therapy was given to the remaining patient, who died within h after icu admission (pjp diagnosis was made post-mortem). adjunctive glucocorticoid therapy was given to ( %) patients based on severity criteria. sixteen patients were switched from tmp-smz to atovaquone (n = ) or pentamidine (n = ), due to acute kidney injury (n = ), myelotoxicity (n = ) allergy (n = ), or hepatic cytolysis (n = ); of these patients had both acute kidney injury and myelotoxicity. of patients with available bal fluid cytology results, ( %) had evident alveolitis profile. mean bal fluid percentages in the patients were . ± . for neutrophils, ± . for macrophages, and ± . for lymphocytes. bacterial co-infection was diagnosed in ( %) patients, viral co-infection in ( %) patients, and fungal co-infection in ( %) patients (additional file : table s ). lymphocytes and neutrophils mean ratio were, respectively, % and % in hiv patients, % and % in non-hiv patients, % and % in dead patients, % and % in survivors patients, % and % with only pjp patients, % and % during coinfection. we did not observe in our study eosinophilic and neutrophilic alveolitis. of the patients, ( . %) were classified as severe pjp (table ) . icu admission was required in patients, including who received mv. the hiv serology was positive in / ( %) patients with severe pjp and / ( %) patients with non-severe pjp. early risk factors associated with severity in the univariate analyses were age > years (or, . ; % ci . - . ; p < . ), albuminemia < g/l (or, . ; % ci . - ; p < . ), blood neutrophil count > . g/l (or, . ; % ci . - ; p < . ), bal fluid neutrophils > % (or, . ; % ci - ; p < . ), p. jirovecii oocysts observed at direct examination of bal fluid (or, . ; % ci . - . ; p < . ), higher baseline lactic dehydrogenase value (or, . ; % ci . - . ; p < . ), and higher crp (or, . ; % ci . - . ; p < . ). a bal alveolitis profile was protective (or, . ; % ci . - . ; p < . ). by multivariate analysis, factors independently associated with severe pjp were older age (or, . ; % ci . - . ; p < . ), p. jirovecii oocysts observed at direct examination of bal fluid (or, . ; % ci . - . ; p < . ) and the absence of a bal fluid alveolitis profile (or, . ; % ci . - . ; p < . ). bmi, body mass index; icu, intensive care unit; ards, acute respiratory distress syndrome; saps , simplified acute physiology score version ; sofa score, sequential organ failure assessment score; hiv, human immunodeficiency virus; pjp, pneumocystis jirovecii pneumonia; crp, c-reactive protein; ldh, lactate dehydrogenase; pj, pneumocystis jirovecii a the total exceeds % because some patients had more than one cause of immunodeficiency b of these patients, followed their prescribed prophylactic regimen (aerosolised pentamidine, n = ; and atovaquone, n = ) and did not (trimethoprim/sulfamethoxazole, n = ; and aerosolised pentamidine, n = ) two factors were independently associated with -day mortality by multivariate analysis, a worse sofa score was associated with higher -day mortality (or, . ; % ci . - . ; p < . ), whereas bal fluid alveolitis profile was associated with lower -day mortality (or, . ; % ci . - . ; p < . ) ( table ) . hiv serology was a protective factor in univariate analysis but was not statistically associated with protective factor in the multivariate -day mortality analysis. in survival analysis hiv patients presenting with pjp was associated with statistically better prognostic than that of patients with hematologic diseases or solid cancer (additional file : figures s , s ) . in the subgroup of hiv-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher -day mortality (or, . ; % ci . - . ; p < . ) (additional file : tables s , s ). factors associated with -day mortality in icu patients were sofa score and non-hiv patients (additional file : table s ). in this prospective study, over four-fifths of pjp patients were hiv-negative, and half met our criteria for severe disease. a worse sofa score on admission and viral co-infection were independently associated with higher -day mortality in both whole patients and hiv-negative patients. importantly, a bal fluid cytological profile consistent with alveolitis was associated with lower -day mortality. severe pjp on admission as defined for our study was associated with a % risk of receiving mv, in keeping with recent results from large cohort studies [ , ] . given the prognostic significance of severity, an improved knowledge of early risk factors for severity is helpful to identify patients requiring more intensive monitoring and treatment. as illustrated here, hiv patients less often experienced severe pjp compared to their hiv-negative counterparts, in agreement with earlier data [ , , [ ] [ ] [ ] [ ] . the reduced severity of pjp in hiv-positive patients is more table risk factors for -day mortality in the overall population (patients where bal was performed, n = ) italics characters correspond to the analysis parameters with a statistically significant difference bmi, body mass index; saps , simplified acute physiology score version , sofa score, sequential organ failure assessment score; hiv, human immunodeficiency virus likely to be associated with the particularity of hivinduced immunosuppression, of which pneumocystis is a hallmark of a severe adaptive cellular impairment. the co-morbidities in non-hiv patients (onco-hematology, solid organ transplantation and system diseases) may also contribute to their greater vulnerability. the immune recovery allowed by the initiation of antiretroviral therapy is probably correlated with better long-term outcomes in hiv-positive patients than in non-hiv patients whose profound immunosuppression is more frequently extended. hiv-positive patients also have lower neutrophil counts in bal fluid samples [ ] , are less likely to develop severe pjp, and have lower mortality rates compared to hiv-negative patients [ , [ ] [ ] [ ] [ ] . the sofa score, viral co-infection and absence of alveolitis remained independently associated with a -day higher mortality in hiv-negative patients, suggesting that it is a strong independent marker in the whole pjp population. by univariate analysis, early risk factors for severity in hiv-negative patients were markers for vulnerability (older age and lower serum albumin) and for inflammation (systemic inflammatory syndrome characterized by blood and alveolar polynucleosis serum crp level). the patient subgroup at the most severe end of the spectrum had the highest crp levels and neutrophil counts, suggesting that anti-inflammatory treatments might improve patient outcomes. our study suggests that future prospective studies on adjunctive treatments for pjp should focus on hiv-negative patients, notably solid organ and haematological stem cell transplant recipients, meeting criteria for severe pjp (e.g., sofa score > with a low pao /fio ratio). the potential relevance of a bal fluid cytology profile consistent with alveolitis should probably also be taken into account when assessing the efficacy of new treatment regimens. as expected, mortality within the first days was significantly higher in patients with severe versus nonsevere pjp. the independent association between a worse sofa score at admission and -day mortality confirms the appropriateness of an evaluation with an intensivist to consider icu admission of patients with oxygen-dependent pjp [ ] . the quicksofa, which is a simplified score based on three criteria, is easy to determine by non-intensivists and may be useful for determining when advice from an intensivist should be sought [ ] . in addition to a worse sofa score, viral co-infection at the time of pjp diagnosis was associated with higher -day mortality. viral infections consisted mostly ( %) in reactivation of latent viruses (cytomegalovirus, herpes simplex virus, or epstein-barr virus), suggesting that this subgroup may have been characterised by a more profound immune deficiency. taken together, this finding supports the hypothesis that the outcome of pjp is also closely related to the underlying diagnosis and immune response. an important finding from this study is the clear association between a bal fluid cytology profile consistent with alveolitis (> % lymphocytes, > % neutrophils, and presence of activated macrophages) and less severe pjp and lower -day mortality. the presence of neutrophils in bal fluid has often been noted in clinical and experimental studies of acute respiratory distress syndrome (ards) [ , ] . three patient subgroups can be identified in our population, one defined by alveolitis, the other one pjp occuring in hiv-positive individuals, both having a better prognosis and the last one defined by a sofa score above on admission who have a more severe prognosis. taken together, these results suggest that specific immunological characteristics might allow the identification of patient subgroups with different treatment needs and outcomes. cd + t cell levels were non-significantly higher in patients with alveolitis, whereas glucocorticoid exposure was comparable in the two groups. to our knowledge, alveolitis during pjp has not been described as a good prognostic factor yet [ ] . in murine models of cd + t-cell depleted mice, increased alveolar recruitment of cd + t cells induced by interleukin- therapy improved p. jirovecii clearance [ ] . lymphocyte count in bal fluid is increased in patients with alveolitis, which was associated with a better prognosis in our study. thus, alveolitis during pjp might reflect maintenance of an effective pulmonary immune response including cd + t-cell recruitment. glucocorticoid therapy might, therefore, be unnecessary in patients with pjp and alveolitis, although their specific response to glucocorticoids has not been investigated to date. four-fifths of our patients had not been prescribed pjp prophylaxis, and among those with a prescription only one-third were compliant. these findings confirm earlier results [ , ] and further identify the absence of tmp/smz prophylaxis as a major risk factor for pjp in high-risk patients [ ] . providing appropriate prophylactic anti-microbial treatments to patients with immunosuppression, notably related to haematological diseases and transplantation, is crucial to improve patient outcomes. adherence to prophylactic treatment must be supported at each follow-up visit. pjp usually develops in patients with cd + counts below /mm [ ] [ ] [ ] , although the depth of lymphopenia does not correlate with pjp severity [ , ] . a history of glucocorticoid exposure is an often reported risk factor for pjp in hiv-negative patients [ , ] . among our patients, over half were receiving glucocorticoid therapy at the diagnosis of pjp, in a mean prednisone-equivalent dosage of mg/day. adjuvant glucocorticoid therapy was given to most severe patients who failed antibiotic treatment alone. given the history of glucocorticoid exposure, the effects of adjuvant glucocorticoid therapy were difficult to assess. the role for adjuvant glucocorticoid therapy in patients with pjp is debated [ , [ ] [ ] [ ] [ ] [ ] and is currently being assessed in a prospective study (clinicaltrials.gov identifier: nct ). serum ldh level at pjp diagnosis was associated with poor outcomes in hiv-positive and hiv-negative patients in several studies [ ] . in our population, ldh > µkat/l ( u/l) levels were associated with severe pjp by univariate analysis but not with higher -day mortality by multivariate analysis. missing data or a role for unidentified confounders may explain this result. a limitation of our study is the use of non-validated criteria for defining severe pjp. the european conference on infections in leukaemia- group has defined severe pjp, like those defined for hiv-positive patients [ ] such as pao less than kpa, oxygen saturation less than %, and radiological impairment. these criteria were only used in retrospective study of pjp patients [ ] . however, these criteria have not been prospectively validated in non-hiv patients. hiv-patients less often experienced severe pjp compared to their hiv-negative counterparts, enhancing the need to propose an early severity scale adapted to this specific population. we, therefore, relied on criteria indicating hypoxemic arf, namely, fio ≥ % or niv or mv. the strong association of severe pjp with higher -day mortality indicates that our definition successfully identified severe pjp. in a large prospective cohort of patients admitted for pjp, the sofa score on admission and presence of viral co-infection were independently associated with higher -day mortality. importantly, a bal fluid cytology profile suggesting alveolitis was associated with less severe pjp and lower -day mortality. our findings, notably the associations linking the sofa score and alveolitis to -day mortality, deserve further evaluation in a multicentre prospective study. future studies of adjunctive treatments for pjp therapy should differentiate 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supplementary information accompanies this paper at https ://doi. org/ . /s - - -x. abbreviations ards: severe acute respiratory distress syndrome; bal: broncho-alveolar lavage; bmi: body mass index; ci: confidence interval; cmv: cytomegalovirus; crp: c-reactive protein; ebv: epstein-barr virus; fio : fraction of inspired oxygen; hiv: human immunodeficiency virus; hsv : herpes simplex virus; icu: intensive care unit; ldh: lactate dehydrogenase; mv: invasive mechanical ventilation; niv: non-invasive ventilation; or: odds ratio; pao : arterial partial pressure of oxygen; pcr: real-time polymerase chain reaction; pjp: pneumocystis jirovecii pneumonia; rsv: respiratory syncytial virus; saps : simplified acute physiology score version ; sd: standard deviation; sofa score: sequential organ failure assessment score; tmp-smx: trimethoprim-sulfamethoxazole.authors' contributions bjg and bt analysed and interpreted the data. cs performed the cytological examinations of broncho-alveolar fluid samples. fm, ral, and bjg were members of the independent committee that adjudicated the pjp cases. bjg and jr wrote the manuscript. all authors read and approved the final manuscript no funding was received for this study. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. all authors read the final version of the manuscript and approved its submission to annals of intensive care. the authors declare that they have no competing interests. key: cord- -dtbm ue authors: malbrain, manu l. n. g.; langer, thomas; annane, djillali; gattinoni, luciano; elbers, paul; hahn, robert g.; de laet, inneke; minini, andrea; wong, adrian; ince, can; muckart, david; mythen, monty; caironi, pietro; van regenmortel, niels title: intravenous fluid therapy in the perioperative and critical care setting: executive summary of the international fluid academy (ifa) date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: dtbm ue intravenous fluid administration should be considered as any other pharmacological prescription. there are three main indications: resuscitation, replacement, and maintenance. moreover, the impact of fluid administration as drug diluent or to preserve catheter patency, i.e., fluid creep, should also be considered. as for antibiotics, intravenous fluid administration should follow the four ds: drug, dosing, duration, de-escalation. among crystalloids, balanced solutions limit acid–base alterations and chloride load and should be preferred, as this likely prevents renal dysfunction. among colloids, albumin, the only available natural colloid, may have beneficial effects. the last decade has seen growing interest in the potential harms related to fluid overloading. in the perioperative setting, appropriate fluid management that maintains adequate organ perfusion while limiting fluid administration should represent the standard of care. protocols including a restrictive continuous fluid administration alongside bolus administration to achieve hemodynamic targets have been proposed. a similar approach should be considered also for critically ill patients, in whom increased endothelial permeability makes this strategy more relevant. active de-escalation protocols may be necessary in a later phase. the r.o.s.e. conceptual model (resuscitation, optimization, stabilization, evacuation) summarizes accurately a dynamic approach to fluid therapy, maximizing benefits and minimizing harms. even in specific categories of critically ill patients, i.e., with trauma or burns, fluid therapy should be carefully applied, considering the importance of their specific aims; maintaining peripheral oxygen delivery, while avoiding the consequences of fluid overload. intravenous fluids have been in clinical use for over a century, yet the medical and scientific community have only recently begun to appreciate the importance of judicious fluid administration, the necessity to handle them as any other drug we prescribe [ ] [ ] [ ] [ ] , and the considerable side effects with which they may be associated [ , ] . three major indications exist for intravenous fluid administration [ , , [ ] [ ] [ ] : resuscitation, replacement, and maintenance. resuscitation fluids are used to correct an intravascular volume deficit or acute hypovolemia; replacement solutions are prescribed to correct existing or developing deficits that cannot be compensated by oral intake alone [ ] ; maintenance solutions are indicated in hemodynamically stable patients that are not able/allowed to drink water in order to cover their daily requirements of water and electrolytes [ , ] . in addition to these classical indications, the quantitative relevance of fluids administered as drug diluents and to guarantee catheter patency, the so-called fluid creep, has been recently underlined [ , ] . although the use of intravenous fluids is one of the most common interventions in medicine, the ideal fluid does not exist. in light of recent evidence, a reappraisal of how intravenous fluids should be used in the perioperative and critical care setting is warranted. here, we present the executive summary on this area of the international fluid academy (https ://www.fluid acade my.org). similarly to antibiotics, the ds of fluid therapy need to be considered (table ) [ ] . fluids are drugs with indications, contraindications, and side effects. different indications need different types of fluids, e.g., resuscitation fluids should focus on rapid restoration of circulating volume; replacement fluids must mimic the fluid that has been lost; maintenance fluids must deliver basic electrolytes and glucose for metabolic needs. the dose makes the poison, as stated by paracelsus. however, timing and administration rate are equally important for fluids [ , ] . of note, in contrast to most drugs, there is no standard therapeutic dose for fluids. the duration of fluid therapy is crucial and volume must be tapered when shock is resolved. however, while "starting triggers" for fluid resuscitation are quite clear, clinicians are less aware of "stopping triggers" of fluid resuscitation. the final step in fluid therapy is to withhold/withdraw fluids when they are no longer required, thus reducing the risk of fluid overload and related deleterious effects [ ] . intravenous "balanced" solutions include crystalloids and colloids with minimal effect on the homeostasis of the extracellular compartment, and in particular on acid-base equilibrium and electrolyte concentrations [ ] . in addition, the term "balanced" has been recently applied also to fluids with a low chloride content (cl − ). therefore, there are two main categories of balanced solutions ( table ): ( ) fluids causing a minimal effect on acid-base equilibrium, having an electrolyte content with an in vivo strong ion difference (sid), i.e., the sid after metabolism of the organic anion, close to - meq/l; ( ) fluids having a normal or sub-normal cl − content (cl − ≤ meq/l). according to the quantitative approach to acid-base equilibrium [ , ] , the three variables regulating the ph of biologic fluids independently are ( ) partial pressure of carbon dioxide (pco ); ( ) the concentration of non-volatile weak acids (a tot ); ( ) the strong ion difference (sid), defined as the difference between the sum of all strong cations and the sum of all strong anions [ ] . these principles clearly suggest that intravenous fluids may affect ph due to (i) the specific electrolyte content characterizing the solution, therefore altering the sid of the extracellular compartment and (ii) the dilution effect due to the volume infused, thus reducing the concentration of a tot [ ] [ ] [ ] . ideally, the fluid able to leave plasma ph unchanged after its administration, at constant pco , should balance these variations. recent studies clearly showed that, in this regard, the ideal balanced solution should have an in vivo sid equal to the baseline concentration of hco − [ ] . if the sid of the infused fluid is greater than plasma hco − , plasma ph will tend toward alkalosis; if the sid of the infused fluid is lower than plasma hco − , plasma ph will tend toward acidosis, as it is always the case for nacl . %, the so-called "normal" saline [ ] . as stated above, the definition of "balanced" solution includes also a category of iso-and near-isotonic fluids with a low cl − content (equal to or lower than meq/l), as compared to nacl . %. nonetheless, the final composition of such a fluid, especially when considering crystalloids, will depend on ( ) tonicity; ( ) electrical neutrality and ( ) sid. indeed, an isotonic balanced solution leaving unaltered acid-base equilibrium (i.e., with an sid close to meq/l) will necessarily have a cl − content > meq/l (as in sterofundin-iso). in contrast, a fluid with an sid of meq/l and a lower cl − content will necessarily be slightly hypotonic (as with lactated ringer's). finally, an isotonic fluid with a low cl − content will necessarily have a higher sid (as with plasmalyte), with a consequent alkalizing effect. [ , ] . on the other hand, in an experimental model of near-fatal hemorrhagic shock, a lower dose of balanced solution was needed, as compared to nacl . % to restore a target blood pressure [ ] . these conflicting results underline the fact that findings about fluid therapy are condition-specific, and that results obtained from septic patients or experimental models should not be extrapolated to all situations. despite these controversies, which need further clarification, several definitive differences exist between these two categories of drugs. first, chloride-rich nacl . % causes a higher dose-dependent degree of acidosis and hyperchloremia, which possibly favors the contraction of vascular smooth muscles [ , ] , potentially leading to a reduced renal perfusion. when healthy volunteers received l of either saline or plasma-lyte over h, saline significantly decreased renal artery blood velocity, decreased renal cortical tissue perfusion, decreased urine output, and increased extravascular fluid accumulation compared with plasma-lyte [ ] . these findings may support the idea that hyperchloremia may cause increased tubule-glomerular feedback and decreased renal cortical perfusion [ ] . indeed, a large-scale propensity-matched observational analysis of u.s. insurance data showed that the use of plasmalyte ® versus nacl . % on the first day of major abdominal surgery led to significantly less renal failure requiring dialysis [ ] . in addition to the effect on renal perfusion, nacl . %, being slightly hypertonic, likely causes an increased incretion of arginine vasopressin. these two effects can conceivably contribute to the slower renal excretion of nacl . % as compared to balanced solutions [ , ] . indeed, more fluid will be retained in the interstitial space, with the consequent propensity to cause more edema [ , ] . however, it is not merely the renal function that could be deranged by high chloride concentrations; infusion of nacl . % can cause abdominal discomfort in healthy volunteers [ ] and a reduced gastric perfusion in elderly surgical patients [ ] . two important and large randomized controlled trials comparing the use of balanced solutions and normal saline have been published in the last years. the split in-vivo sid-all organic molecules contained in balanced solutions are strong anions. the resulting calculated sid (in vitro-sid) is equal to meq/l, due to electrical neutrality. once infused, the organic molecules are metabolized to co and water; the resulting in vivo-sid corresponds to the amount of organic anions metabolized a sterofundin-iso or ringerfundin b in vivo-sid of tetraspan reported in the table results from the sum of organic anions; of note, there is a discrepancy as compared to the sid calculated as the difference between inorganic cations and inorganic anions ( meq/l vs. meq/l). no study was the first multi-center double-blind randomized controlled trial performed on patients, comparing balanced and unbalanced fluids in intensive care units. it showed no significant difference in the main outcome, i.e., incidence of acute kidney injury [ ] . while providing a high level of evidence, this trial did not give a definitive answer. indeed, the median volume of study fluid was only l over days. moreover, both study groups had received a median volume of . - . l of plasmalyte within h prior to enrolment, therefore making it plausible that prior administration of plasmalyte counterbalanced the effects of low-dose nacl . %. the smart-trial was a large study performed in five intensive care units of a single academic center [ ] . a total of , patients were randomized to receive either nacl . % or a balanced solution (plasma-lyte a or lactated ringer's). in both groups, patients received an extremely small amount of fluids: a median of l from admission to day or discharge, whichever came first. despite the unexpectedly low volume of crystalloids, the authors found a small difference in the primary outcome, i.e., the incidence of major adverse kidney events within days (composite of death, new renal replacement therapy or persistent renal dysfunction) in favor of balance solutions. looking at the overall outcome, it is important to emphasize that there was no reduction of in-hospital mortality and that neither the incidence of renal replacement therapy ( . % vs. . %, p = . ) nor the incidence of persistent renal dysfunction ( . % vs. . %, p = . ) was statistically significant. a similar study performed by the same authors and published in the same issue of the new england journal of medicine, the salt-ed trial, found a similar difference in the incidence of major adverse kidney events in noncritically ill adults [ ] . in summary, we can avoid fluid-induced metabolic acidosis and excessive chloride loading simply using balanced solutions. there is increasing evidence that an excessive chloride administration may have a detrimental effect on renal function, even at low doses. therefore, the use of balanced solutions, particularly in patients that potentially need a significant amount of intravenous fluids, seems to be a reasonable pragmatic choice [ ] . on the contrary, saline may be an intuitive choice for patients with hypovolemic hyponatremia or hypochloremic metabolic alkalosis. in any other settings, the most important reason to choose nacl . % over balanced solutions is likely economic in nature. therefore, the patient's serum chloremia is an important factor to determine the appropriate type of fluids. albumin accounts for approximately % of the plasma protein content [ ] and is the main determinant of plasma oncotic pressure, playing a crucial role in the regulation of microvascular fluid dynamics [ , ] . normal plasma concentration of albumin ranges between and g/l, corresponding to approximately . - . mmol/l, and to an in vitro pressure of approximately . mmhg. in contrast, in vivo colloid-oncotic pressure is lower, since the permeability of the endothelial barrier to albumin is variable, even in healthy subjects. nonetheless, according to starling's law, oncotic pressure is the force counteracting intravascular hydrostatic pressure, therefore acting to reabsorb water and small solutes from the interstitium to the intravascular space. the crucial role of albumin's oncotic property in the regulation of microcirculatory fluid dynamics also seems to apply to the endothelial glycocalyx layer [ , ] . this gel-like layer, lining the luminal side of the endothelium, is thought to comprise % of the intravascular volume. the current view of the glycocalyx is that it holds many compounds that are mandatory for the functioning of the endothelium and mediates several key physiological processes, such as maintaining the vascular barrier, hemostasis, prevention of cell adhesion to the endothelium and transmission of shear stress [ ] . the role of the glycocalyx is however under continuous investigation and its role and function might need to be revised in the future [ ] . of note, shedding of the glycocalyx occurs in the presence of reactive oxygen species, hyperglycemia, cytokines, and endotoxin, and is therefore common in critically ill patients [ ] . in the context of fluid homeostasis, loss of barrier function induced by glycocalyx shedding is associated with the formation of edema [ ] . furthermore, fluid therapy itself is known to be potentially deleterious for endothelial function [ ] , likely because of the resulting oxidative stress. however, the risks probably relate to the specific clinical context. indeed, while volume loading did not cause glycocalyx shedding in surgical patients and healthy volunteers [ , ] , the amount of glycocalyx shedding was proportional to the volume of fluid given in septic shock patients [ ] . the albios study, a large italian randomized controlled trial, gave some suggestions on whether or not albumin administration improves outcomes in severe sepsis and septic shock [ ] . patients with severe sepsis were randomized to receive either % albumin and crystalloids or crystalloids alone after initial early goal-directed resuscitation. in patients randomized to albumin treatment, albumin was supplemented for days, to maintain an albumin concentration ≥ g/l. despite some beneficial physiologic effects (lower heart rates, higher mean arterial pressure, and lower daily net positive fluid balance over the first days), no difference was observed either in mortality at days ( . % vs. . %) or in overall organ failure scores. however, when analyzing the results according to disease severity, patients with septic shock randomized to albumin supplementation showed a lower risk of death (relative risk . ; % confidence interval-ci . - . ) as compared to those just receiving only crystalloids. it is worth mentioning that this trial did not utilize albumin as a resuscitation fluid, but as a drug to correct hypoalbuminemia. colloids should remain in the intravascular space longer than crystalloids, provided that the endothelial barrier is intact, which is often not the case in critically ill patients [ ] . given the recent discussion on the potential adverse effects of artificial colloids, especially of hydroxyethyl starches (hes), a renewed interest in the use of albumin has emerged. however, despite the strong physiologic rationale and significant scientific effort [ , ] , to date, no randomized controlled trial has shown any significant benefit of fluid resuscitation using albumin over other types of fluids, including crystalloids [ ] . some reports have even suggested that albumin administration in the setting of cardiac surgery may be associated with the development of acute kidney injury [ ] . as stated previously, one of the largest albumin trials to date, the albios study, reported a reduction in -day mortality in a subgroup of patients with septic shock. however, this result was based on a post-hoc rather than predefined analysis and should, therefore, be interpreted with caution. the results of two ongoing randomized trials, the albumin italian outcome septic shock-balanced trial (albioss-balanced) and the albumin replacement therapy in septic shock (ariss), may provide some answers to the above-mentioned issues. the significant cost and the availability of equally effective low-cost alternatives do not play in favor of albumin, although a subgroup analysis of the albios dataset may suggest that albumin infusion is likely cost-effective in patients' septic shock [ ] . up to date, the theoretical benefits of albumin are not supported by sound clinical evidence, and the case for albumin remains controversial. the aim of perioperative fluid therapy, in parallel with the maintenance of the effective circulating blood volume, is to avoid both fluid overload and under-hydration, while maintaining patients' fluid balance as close as possible to zero. despite this rationale, it is not unusual for surgical patients to receive - l of fluid and - mmol of sodium, leading to edema and adverse outcomes [ ] , which is also favored by the marked and mean arterial pressure-dependent reduction of the elimination capacity of crystalloids [ , ] . on the other hand, overnight fasting and bowel preparation, when traditionally applied, lead to fluid deficits. apparently, patients develop postoperative complications when fluid retention exceeds . l [ , ] . of course, fluid gain depends not only on the amount of fluid administered, but also on the capacity of the kidney to excrete the excessive fluid and salt [ ] . fluid therapy is not only meant to compensate intraoperative losses but should also take into account those occurring prior to surgery, induced by poor water intake, bowel preparation, major inflammation associated with a stress response, and possibly, hemorrhage. dehydration, however, is difficult to detect through clinical methods. many studies examined whether a fluid load is capable of reducing hypotension caused by the induction of general/regional anesthesia. however, results regarding a preload strategy have been discouraging [ , ] . in response to the ongoing administration of large volumes of crystalloid to patients undergoing major surgery, a 'fluid restrictive' strategy has been proposed. for example, brandstrup et al. demonstrated in a multicenter randomized controlled trial that a more restrictive regimen was associated with better outcomes following colorectal surgery [ ] . however, the regimen was restrictive compared with the standard of care that was excessive (e.g., l positive balance due to high crystalloid volumes) [ ] . it is therefore conceivable that the group with a better outcome rather benefitted from the avoidance of fluid excess than from fluid restriction. the interpretation of the literature on the topic is hampered by the use of very heterogeneous definitions [ ] . what is however clear from observational studies is that both too much and too little fluid are associated with poor outcomes [ ] [ ] [ ] [ ] . recently, a large cohort study from u.s. hospitals including adult patients having colon, rectal or primary hip or knee surgery was concluded [ ] . a significant association was found between liberal fluid administration on the day of surgery and worse outcomes (increased total costs and length of stay in all patients), as well as increased presence of postoperative ileus, in patients undergoing colorectal surgery. interestingly, the authors also observed that restrictive fluid utilization (the lowest % by volume) was also associated with worse outcomes. it is common in enhanced recovery after surgery (eras) protocols to find the term "intraoperative fluid restriction" [ ] . however, alternative terms, such as "zero balance" or the avoidance of salt and water excess, are also available. protocols advocate the infusion of balanced crystalloid of - ml/kg/h and to give additional boluses of fluid only to match needs judged by either measured volumes lost during surgery, or the assessment of peripheral perfusion (such as according to the so-called 'goal-directed fluid restriction') [ ] . overall, the literature suggests that algorithm-based perioperative fluid regimens result in improved patient outcomes. fluid management in postoperative patients is a key determinant of their outcomes. while restoring effective volume is critical for these patients, fluid management should not compromise healing processes. optimal fluid management should thus target efficient central hemodynamics and tissue perfusion while avoiding positive net fluid balance. in theory, colloids offer the advantages over crystalloids of higher plasma expansion capacity and longer plasma half-life. they have the theoretical disadvantage of delaying clotting time and increasing the risk of kidney injury. in randomized trials, the ratio of the cumulative dose of colloids over the cumulative dose of crystalloids ranged roughly from . to [ ] . in patients with overt clinical hypovolemia, colloids were superior to crystalloids in improving cardiac filling pressures and performance [ ] . likewise, in a large multinational randomized trial performed in critically ill patients with acute hypovolemia, colloids reduced vasopressor and ventilator dependency when compared to crystalloids [ ] . a recent systematic review of resuscitation with hes in surgical critically ill patients identified randomized trials [ ] . however, this review found no statistically significant difference between hes and crystalloids, in terms of mortality (risk ratio . ; % ci . to . ; i = %), need for renal replacement therapy (risk ratio . ; % ci . to . ; i = %), and major infectious complications (risk ratio . ; % ci . to . ; i = %). it is worth mentioning that eligible trials were too small to draw firm conclusions on this issue. it should also be stated that there are opposing views regarding the use of starches [ ] . for example, several criticisms regarding the chest trial have been put forward which still require to be addressed [ , ] . furthermore, it can be stated that in the chest trial starches were administered to patients that were not hypovolemic. on the other hand, the cristal trial (where % of the colloid group received hes) concluded that significantly less volume was required to achieve hemodynamic stability for hes vs. nacl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups [ ] . taking these opposing views into consideration, the ongoing debate about the use of starches in hypovolemic critically ill patients still requires more data. among patients undergoing major abdominal surgery, the recent results of the flash trial, showed no significant difference in a composite outcome of death or major postoperative complications within days after surgery [ ] . pending the results of ongoing trials, there are currently insufficient data to ban the use of colloids in the surgical intensive care unit. many patients undergoing surgery are not able to ingest food or fluids for some time following surgery and will require maintenance fluids. recently, a debate emerged on the tonicity of these solutions: although guidelines traditionally recommended the use of hypotonic maintenance fluids, in pediatric literature, these were shown to be associated with an increased incidence of symptomatic hyponatremia [ , ] . the recent randomized controlled topmast trial in adults undergoing major thoracic surgery found this problem to be mild in these patients. isotonic maintenance fluids, on the other hand, were associated with a considerably larger positive cumulative fluid balance (estimated at . l more positive under fluids containing compared to mmol/l of sodium) [ ] . the problem with fluid overload in the perioperative setting a certain degree of hypervolemia is necessary to maintain organ perfusion during anesthesia and surgery. however, fluid given after the induction of anesthesia mainly increases "unstressed" blood volume, because vasodilatation occurs as a consequence of anesthesia. at this point, additional fluid administration is needed to optimize stroke volume, i.e., to add to the "stressed" intravascular volume [ ] . many clinicians still consider this "wet" approach as the gold standard for intraoperative fluid therapy [ ] , although intravascular volume expansion certainly bears some dangers. myocardial work and cardiac pressures increase when infused fluids have exceeded the degree of anesthesia-induced vasodilatation. moreover, fluid overload reduces the colloid osmotic pressure that, together with raised cardiac pressures, might promote pulmonary edema [ ] . these issues are of particular relevance in patients with poor cardiovascular status. finally, hypervolemia may be responsible for another important effect: the release of atrial natriuretic peptides (anps) to the circulation caused by the stretching of atrial myocardial fibers [ , ] . indeed, in response to a rapid infusion of crystalloids, anp levels increase -to -fold [ ] [ ] [ ] , therefore reducing strain on the circulation by promoting natriuresis and capillary leakage of albumin. fluid administration is one of the cornerstones of hemodynamic resuscitation in critically ill patients. how much fluid to give has been the subject of lively debate over the years. too much fluid can have harmful consequences on multiple organ systems, e.g., worsening gas exchange, renal function and wound healing. fluid overload is particularly likely to arise in conditions when capillary permeability is altered due to an inflammatory response, such as during sepsis. a positive fluid balance has been associated with worse outcomes in several studies in various groups of intensive care unit (icu) patients [ , [ ] [ ] [ ] . in patients with septic shock, fluid administration and positive fluid balance were independently associated with increased mortality rates [ , ] . similarly, in patients admitted to the icu after major surgery, fluid balance was an independent risk factor for death [ ] . indeed, a multimodal restrictive fluid strategy aiming for negative fluid balance (pal-treatment) in patients with acute lung injury (ali) was associated with improved outcomes in a retrospective study [ ] . it has to be acknowledged that a positive fluid balance could be a marker of disease rather than a pure iatrogenic or preventable problem and it would be erroneous to assume the default position of underresuscitation. indeed, inadequate resuscitation due to insufficient fluid administration may result in poorer tissue perfusion and hence organ dysfunction and failure, particularly in the early phase of treatment. a balance needs to be achieved, such that each patient receives sufficient, but not excessive, fluid for her/his needs. crucially, different patients will have different needs and baseline fluid status depending on multiple factors including age, co-morbid disease and current diagnosis. in addition, it is mandatory to consider indices of fluid tolerance, such as cvp, lung water, oxygenation and hemoglobin levels. fluid requirements vary during the course of illness. as such, fluids must be prescribed on an individual patient basis; the prescription should be regularly reviewed and tailored to the evolving clinical stage. the answer to the question of whether fluid overload is a problem in the icu will thus depend on when it is asked. in the acute resuscitation/ salvage phase, fluid administration is generous. while fluid overload should always be a concern, a positive fluid balance is a specific target of this phase. the term deresuscitation/de-escalation was first suggested in [ ] and finally coined in [ ] . it specifically refers to 'late goal-directed fluid removal' , which involves "aggressive and active fluid removal through diuretics and renal replacement therapy with net ultrafiltration". deresuscitation/de-escalation is sometimes also used to more loosely refer to the phase of critical illness and/or the care of a critically ill patient, after initial resuscitation, stabilization, and optimization. it is characterized by the discontinuation of invasive therapies and a reduction of a spurious fluid balance. late conservative fluid management is defined as consecutive days of negative fluid balance within the first week of icu stay, and is an independent predictor of survival in icu patients [ ] . fluid overload and a positive cumulative fluid balance are associated with increased morbidity and worse outcomes, as previously discussed. the natural course of events after a first insult (such as infection, trauma, etc.) is a systemic inflammatory response with increased capillary permeability and organ dysfunction [ ] . the presence of fluid overload and interstitial edema may thus trigger a vicious cycle. this is what has been referred to as the ebb phase of shock [ ] . in the majority of patients, shock reversal occurs (with correct antibiotics and proper source control) and excess fluids can be mobilized: this is called the flow phase [ ] . however, some patients will not transfer spontaneously from the ebb to flow phase and will remain in a state of unresolved shock with positive cumulative fluid balance, and this is where active deresuscitation/de-escalation might have an important role. it is unclear which is the best therapeutic option for deresuscitation/de-escalation. the administration of albumin in combination with diuretics ( % albumin to achieve a serum albumin levels of g/l and furosemide bolus of mg followed by continuous infusion of mg/h) and the association of this strategy with the sequential application of peep set to counteract intraabdominal pressure (iap) have been proposed [ ] . in addition, renal replacement therapy and aggressive ultrafiltration can be used to achieve a negative fluid balance in selected patients [ ] . when it comes to deresuscitation/de-escalation, it is important to decide on when, how and for how long. for this purpose, we need to use the right targets to reach our goals. "over-deresuscitation" has its drawbacks and may cause neurologic dysfunction in the long run [ ] . in conclusion, it is crucial to ensure that the indication for fluid resuscitation no longer exists (e.g., absence of vasopressor, no lactate, adequate venous oxygen saturation of hemoglobin) before starting with deresuscitation. furthermore, the steps of deresuscitation/de-escalation need to be kept in mind: ( ) define a clinical endpoint (e.g., improvement in oxygenation); ( ) set a fluid balance goal (e.g., l negative balance in h); ( ) set perfusion and renal safety precautions (e.g., vasopressor need, % serum creatinine increase); ( ) re-evaluate after h unless safety limits reached; ( ) adjust the plan accordingly. two articles were published recently, almost simultaneously, referring to the dynamics of fluid therapy [ , ] . these conceptual models identified four dynamic phases. the acute dialysis quality initiative (adqi) group proposed s.o.s.d. (salvage, optimization, stabilization, de-escalation) as acronym [ ] . however, during the international fluid academy day (ifad) meetings there was a clear preference for the r.o.s.e. acronym (resuscitation, optimization, stabilization, evacuation) as summarized below, in fig. and table . we tried to suggest endpoints and targets for the different phases; however, it was decided not to include them because there cannot be a specific target of cardiac index and ppv must be considered only if cardiac output is low. a high ppv is often a physiological state and defining a "normal" state when a low ppv value is reached might lead to unnecessary fluid infusion [ ] . also, defining a given preload level as a target of resuscitation is senseless as it may shift from patient to patient and from time to time. in the first, salvage/resuscitation phase, when a patient presents with hemodynamic shock, the aim of the treatment is resuscitation and correction of shock with the achievement of an adequate perfusion pressure. a rapid fluid bolus should be given (although the exact amount can vary, usually - ml/kg given over to min and repeated when necessary), normally in association with vasopressor administration. in parallel, emergency procedures to resolve any obvious underlying cause should be performed, with hemodynamic monitoring initiated. in this phase, the goal is early adequate goal-directed fluid management: fluid balance must be positive. we do not support blind adherence to the surviving sepsis campaign guidelines adagio to administer ml/kg of fluids within the first hour for all patients, as explained previously [ ] . this may lead to either over-or under resuscitation in some patients. every patient needs an individual and personalized approach. the optimization phase starts when the patient is no longer in overt absolute/relative hypovolemia, but remains hemodynamically unstable. some form of monitoring will by now be in place. fluids should be administered according to individual needs, reassessed on a regular basis, e.g., using fluid challenge techniques [ , ] . fluid challenges must be conducted carefully, bearing in mind the four essential components (trol): type of fluid (e.g., a balanced crystalloid-like plasmalyte); rate (e - ml over min); objective (e.g., normal arterial pressure or heart rate); and limits (e.g., high central venous pressure level) (fig. ) [ ] . the aim of this phase is to optimize and maintain adequate tissue perfusion and oxygenation in order to prevent and limit organ damage. the patient must be carefully monitored during the optimization phase: often several types of monitoring (e.g., arterial catheter, echocardiography, central venous pressure, arteriovenous blood gas) are required to obtain the most complete picture of a patient's hemodynamic status. although a resuscitation based on microcirculatory endpoints is expected to result in analogous amelioration in the microcirculation, a lack of coherence may exist between macro-and microcirculation. thus, markers of hypoperfusion should include also lactate, prolonged capillary refill time and mottling score [ ] . once the patient is stable, the stabilization phase begins and evolves over days. in this phase, the aim of fluid management is to ensure water and electrolytes to replace ongoing losses and provide organ support. the target should be a zero or slightly negative fluid balance. it might be of interest, in this context, to underline the weeks fact that in the major trials suggesting a harmful effect of starches [ , ] , these colloids were given abundantly also in the stabilization phase, i.e., in a phase that possibly did not require these drugs. the final phase is evacuation or de-escalation, with the purpose of removing excessive fluid. this will be frequently achieved by spontaneous diuresis as the patient recovers, although ultrafiltration or diuretics might be necessary. of note, it was recently shown that diuretics might favor the recruitment of microcirculation, thus decreasing diffusion distances and improving oxygen extraction [ ] . fluid management in acute hemorrhagic shock following trauma although traumatic brain injury remains the commonest cause of death following severe blunt injury, concomitant major hemorrhage will result in cerebral hypoperfusion, which undoubtedly contributes to secondary brain injury and death. as such, hemorrhage remains the most preventable cause of trauma mortality. an adequate intravascular volume, hemoglobin concentration and oxygen saturation are essential to maintain aerobic metabolism. humans do not tolerate anaerobic metabolism and % of oxygen consumption is used in the formation of adenosine triphosphate (atp), the major energy source for cell function. rapid reversal of anaerobic metabolism is imperative to restore atp and prevent irreversible cellular apoptosis and death [ ] . recognizing that hypovolemia is the consequence of hemorrhagic shock, past strategies utilized crystalloids to restore intravascular volume, followed by blood transfusion. crystalloids, however, do not carry oxygen, and oxygen delivery may only be enhanced by an adequate hemoglobin concentration. furthermore, major hemorrhage is accompanied by a unique coagulation disorder, the acute coagulopathy of trauma and shock (acots) [ ] , leading to poor clot formation, as a result of increased binding of thrombin to thrombomodulin and enhanced fibrinolysis. dilution of coagulation factors, acidosis, and hypothermia play a secondary role in this scenario. the approach to resuscitation must therefore be proactive and not reactive with the combined administration of packed red blood cells, plasma, platelets, and cryoprecipitate. the use of clear resuscitation fluids should be minimized. based on military experience, the recommended ratio of packed red blood cells to plasma and platelets should be : : . the endpoints for hemoglobin concentration of g/dl, a platelet count of > , , an inr < . and a fibrinogen concentration of > g/l cannot be generally recommended. in addition, the ionized calcium level should be > . mmol/l. while the above is a general recommendation, not all patients will require such an aggressive approach [ ] . indeed, over-zealous transfusion is associated with unwanted complications. the standard approach has been to use conventional laboratory coagulation testing to determine the need for component therapy. these, however, are performed at room temperature and do not reflect individual steps in coagulation. thromboelastometry has now been recognized as an essential tool to monitor coagulopathy in trauma [ ] . this device reflects the entire process of coagulation and can graphically determine the need for specific coagulation factors. unlike laboratory coagulation studies, modern thromboelastometry machines may be set to the patient's core temperature and accurately reflect the in vivo coagulation status. these instruments should be the standard of care in centers handling major trauma. following the crash- trial indicating the benefit of tranexamic acid given within h from injury, such treatment has been included in many protocols for major hemorrhage [ ] . in the presence of a sophisticated trauma system, the benefits are doubtful and further data are warranted [ ] . the understanding of burn shock pathophysiology and subsequent development of fluid resuscitation strategies resulted in dramatic outcome improvements in burn care during the last decades [ ] . however, while under-resuscitation has become rare in clinical practice, there is growing concern that over-resuscitation, leading to increased morbidity and mortality, has become more of an issue in burn care. in the late sixties of the previous century, baxter and shires developed their landmark formula at the parkland memorial hospital, which has lasted decades as the gold standard for fluid resuscitation in acute burn care across the world [ ] . the formula advocates ml crystalloids per kg per % of total body surface area for h, of which half is given during the first h. diuresis (target ml/kg/h) is used to guide the amount of intravenous fluids. during the second h of resuscitation, colloids are allowed, and resuscitation volume is adapted according to diuresis (with a gradual decrease if diuresis is adequate). however, over the last years, multiple centers have reported excess fluid administration [ , ] . this fluid excess often leads to "resuscitation morbidity", a group of complications linked to fluid overload, such as delayed wound healing, delayed recovery of gastrointestinal function (with ileus), pulmonary edema (due to capillary leak and increased extravascular lung water), limb compartment syndrome, orbital compartment syndrome, intra-abdominal hypertension and abdominal compartment syndrome leading to multiple organ failure [ ] [ ] [ ] . this discrepancy between the predicted and the administered fluid is known as "fluid creep", a term brought to life by basil pruitt [ ] . recommendations for fluid resuscitation in burns are listed in table . the most well-known adverse effect of nacl . % is hyperchloremic metabolic acidosis. given the large infusion volumes administered to burn patients, balanced solutions are preferred. indeed, since the beginning of burn resuscitation, most formulae advocate the use of balanced crystalloid solutions. of note, an observational study reported lower sequential organ failure assessment (sofa) scores in severely burned patients resuscitated with acetated ringer's [ ] . the use of colloids in the first h has been controversial since it was thought that the existing capillary leak would allow large molecules to leak out into the extravascular space and exert an osmotic pull increasing the formation of edema [ ] . in the last years, renewed interest in colloids has arisen during burn resuscitation, instigated by the awareness of morbidity related to resuscitation and fluid creep. until recently, the low molecular weight hes solutions were widely used as a resuscitation fluid in critically ill icu, surgery and burn patients. however, after large fluid trials, including the chest and s trials, showing increased mortality and a higher rate of renal replacement therapy have raised alarming conclusions regarding the safety of hes solutions, starches can no longer be used in burn injuries as recommended by the pharmacovigilance risk assessment committee (prac) [ , , ] . albumin is a natural plasma protein that contributes most to intravascular oncotic pressure in humans (see above). the most common solutions are %, % or % albumin. it is a relatively expensive solution and its availability may be limited in some countries. although albumin resuscitation has been used with some reservations, especially in the acute phase of burn resuscitation, trials provide promising data regarding the use of albumin as an adjunctive therapy in burn resuscitation [ , ] . similarly, hypertonic saline has been used for decades in burn resuscitation; theoretically, it expands the circulating volume by an intravascular water shift. proponents claim that this process will decrease tissue edema and will lower the rate of complications. this hypothesis, however, needs to be confirmed by further studies. consider the ps of fluid prescription as shown in fig. and tailor the iv fluids to the patient's need via individualized and personalized care (table ) [ ] . prescription safety can be summarized by the ' ds' principle as explained above [ ] : the bottom line is "give the right fluid in the right dose to the right patient at the right time" the prescription of fluid therapy is one of the most common medical acts in hospitalized patients but many of the aspects of this practice are surprisingly complex. it is time to introduce fluid stewardship in your icu. the physician should engage in writing a prescription that accounts for drug, dose, duration and whenever possible de-escalation. c pharmacy: the prescription is sent to the pharmacy and is checked for inconsistencies by the pharmacist to get a more holistic view. d preparation: the process by which the prescription is prepared and additions (e.g., electrolytes) made. e patient: the filled prescription goes back to the patient and fluid stewards should observe administration, response, and debrief to avoid fluid-induced harm, we recommend a careful evaluation of the chosen solution and a phase-wise approach to its administration, taking into account the clinical course of the disease or surgical procedure. fluids should be prescribed with the same care as any other drug and every effort should be made to avoid their unnecessary administration. c. replacement and redistribution if patients have ongoing abnormal losses or a complex redistribution problem, the fluid therapy is adjusted for all other sources of fluid and electrolyte losses (e.g., normal saline may be indicated in patients with metabolic alkalosis due to gastro-intestinal losses) d. fluid creep all sources of fluids administered need to be detailed: crystalloids, colloids, blood products, enteral and parenteral nutritional products, and oral intake (water, tea, soup, etc.) precise data on the concentrated electrolytes added to these fluids or administered separately need to be collected fluid creep is defined as the sum of the volumes of these electrolytes, the small volumes to keep venous lines open (saline or glucose %), and the total volume used as a vehicle for medication the following information is included in the iv fluid prescription: the type of fluid the rate of fluid infusion the volume or dose of fluid the iv fluid prescription is adapted to current electrolyte disorders and other sources of fluid intake patients have an iv fluid management plan, including a fluid and electrolyte prescription over the next h the prescription for a maintenance iv fluid only changes after a clinical exam, a change in dietary intake or evaluation of laboratory results fluid management before, during and after elective surgery hydroxyethyl starch / . versus ringer's acetate in severe sepsis intravenous balanced solutions: from physiology to clinical evidence it is time to consider the four d's of fluid management association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults resuscitation fluids national institute for h, care excellence guideline development g. intravenous fluid therapy for adults in hospital: summary of nice guidance intravenous fluid therapy for hospitalized and critically ill children: rationale, available drugs and possible side effects principles of fluid management and stewardship in septic shock: it is time to consider the four d's and the four phases of fluid therapy effect of isotonic versus hypotonic maintenance fluid therapy on urine output, fluid balance, and electrolyte homeostasis: a crossover study in fasting adult volunteers maintenance intravenous fluids in acutely ill patients maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed icu population normal saline to dilute parenteral drugs and to keep catheters open is a major and preventable source of hypernatremia acquired in the intensive care unit mortality after fluid bolus in african children with severe infection unintended consequences: fluid resuscitation worsens shock in an ovine model of endotoxemia fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice independent and dependent variables of acid-base control stewartìs textbook of acid-base lulucom electrolyte shifts across the artificial lung in patients on extracorporeal membrane oxygenation: interdependence between partial 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springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations mlngm and nvr are co-founders of the international fluid academy (ifa). this open access article is endorsed by the ifa. the mission statement of the ifa is to foster education, promote research on fluid management and hemo- ds: drug-dose-duration-de-escalation; anp: atrial natriuretic peptide; atp: adenosine triphosphate; ci: confidence interval; eras: enhanced recovery after surgery; hes: hydroxyethyl starch; iap: intra-abdominal pressure; icu: intensive care unit; peep: positive end-expiratory pressure; rose: resuscitation-optimization-stabilization-evacuation; sid: strong ion difference; sofa: sequential organ failure assessment. mlngm wrote the concept. mlngm wrote first draft. all other authors reviewed and edited the manuscript. all authors read and approved the final manuscript. dr. manu malbrain is professor at the faculty of medicine and pharmacy at the vrije universiteit brussels (vub) and member of the executive committee of the abdominal compartment society, formerly known as the world society of abdominal compartment syndrome (https ://www.wsacs .org/). he is a cofounder, past-president and current treasurer of wsacs. he is a co-founder of the international fluid academy (ifa). not applicable. not applicable. not applicable. not applicable. key: cord- -jr d authors: joseph, adrien; zafrani, lara; mabrouki, asma; azoulay, elie; darmon, michael title: acute kidney injury in patients with sars-cov- infection date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: jr d background: acute kidney injury (aki) is a frequent complication of severe sars-cov- infection. multiple mechanisms are involved in covid- -associated aki, from direct viral infection and secondary inflammation to complement activation and microthrombosis. however, data are limited in critically-ill patients. in this study, we sought to describe the prevalence, risk factors and prognostic impact of aki in this setting. methods: retrospective monocenter study including adult patients with laboratory confirmed sars-cov- infection admitted to the icu of our university hospital. aki was defined according to both urinary output and creatinine kdigo criteria. results: overall, covid- patients were admitted. aki occurred in patients ( %), including , and patients with aki stage , and respectively. the severity of aki was associated with mortality at day (p = . ). before adjustment, the third fraction of complement (c ), interleukin- (il- ) and ferritin levels were higher in aki patients. after adjustment for confounders, both severity (modified sofa score per point) and aki were associated with outcome. when forced in the final model, c (or per log . ; % ci . – . ), il- (or per log . ; % ci . – . ), or ferritin (or per log . ; % ci . – . ) were not associated with aki and did not change the model. conclusion: in conclusion, we did not find any association between complement activation or inflammatory markers and aki. proportion of patients with aki during severe sars-cov- infection is higher than previously reported and associated with outcome. since december , severe acute respiratory coronavirus (sars-cov- ) has spread worldwide, causing more than . million cases and deaths [ ] . this pandemic has put unprecedented pressure on healthcare systems and especially on intensive care units (icus). acute kidney injury (aki) is a frequent complication of severe sars-cov- infection but data are scarce in icus. aki has been previously reported with an average incidence of % ( - %) overall, with highest ranges in the critically ill ( %; - %) [ ] [ ] [ ] . different applications of the kidney disease improving global outcomes (kdigo) criteria for aki, in particular different methods to estimate missing baseline creatinine and handling urinary output, can cause important variations of estimated incidence [ , ] and may contribute to the discrepancies among these studies. multiple mechanisms are involved in covid- -associated aki, ranging from direct viral infection of the kidney and secondary inflammation to complement activation and microthrombosis [ ] . in particular, severe covid- is associated with uncontrolled systemic inflammatory response with high levels of il- [ ] that could potentially lead to intrarenal inflammation and increased vascular permeability and share several features with hyperferritinemic syndromes such as open access *correspondence: lara.zafrani@aphp.fr service de médecine intensive et de réanimation médicale, hôpital saint-louis, assistance-publique hôpitaux de paris, paris university, avenue claude vellefaux, paris, france full list of author information is available at the end of the article macrophage activation syndrome [ ] . furthermore, unrestrained activation of complement leads to endothelial cell dysfunction and intravascular coagulation that could participate in covid- -associated aki [ ] . both il- [ ] and complement [ ] have been proposed as therapeutic targets and understanding their role in covid- -associated aki is therefore a priority. however, most of the studies performed to date gave little data regarding definition of aki or influence of inflammation and complement markers on aki. in this study, we sought to describe the prevalence, risk factors and prognostic impact of aki during covid- in the icu. we conducted a retrospective monocenter study including adult patients with laboratory confirmed sars-cov- infection admitted to the icu of our university hospital. all adult patients (age ≥ years) who tested positive by polymerase chain reaction testing of a nasopharyngeal sample for covid- and were hospitalized from march , to june , were eligible. this study was approved by an institutional review board (french intensive care society-ce srlf n° - ). need for informed consent was waived as regard to the study observational design and in accordance with the french law. this study was conducted in accordance with the principles of the declaration of helsinki. all data were obtained from medical records and patients' charts. baseline patients' characteristics were collected, including demographics and comorbidities before icu admission. the variables recorded regarding icu admission and treatments were relative to clinical presentation, reason for icu admission, diagnosis, therapies implemented and outcomes. blood sampling and routine biological testing were performed on the day of admission according to the standard laboratory protocols. all samples were immediately centrifuged at rpm at °c for min, separated from the cells and stored at − °c until biochemical assays of complement proteins c , c (nephelometry) and sc b (elisa), il- (elisa) were performed. the primary outcome was mortality at day . aki was defined according to both urinary output and serum creatinine kdigo criteria [ ] as follows: stage -increase in serum creatinine by . mg/dl within h or a . - . times increase in serum creatinine from baseline or urinary output < . ml/kg/h for - h within days; stage - . times increase in serum creatinine or urinary output < . ml/kg/h for ≥ h within days; stage - times or more increase in serum creatinine or to ≥ . mg/dl or initiation of rrt or urinary output < . ml/kg/h for ≥ h or anuria for ≥ h within days. patients were stratified according to the highest aki stage attained during the first days of icu stay. baseline creatinine was defined as the best value in the preceding months or if unavailable as the lowest value during icu stay or was back calculated based on a glomerular filtration rate of ml/min/ . m with mdrd equation in patients without known chronic kidney disease. chronic kidney disease (ckd) was defined according to the kdigo definition. modified sofa was defined as sofa score [ ] excluding the renal component. continuous variables were described as median (interquartile range [iqr] ) and compared between groups using the non-parametric wilcoxon rank-sum test. categorical variables were described as frequency (percentages) and compared between groups using fisher's exact test. mortality was assessed using survival analysis. independent risk factors of day mortality were assessed using cox model. conditional stepwise variable selection was performed with . as the critical p-value for entry into the model, and . as the p-value for removal. interactions and correlations between the explanatory variables were carefully checked. validity of proportional hazards assumption, influence of outliers, and linearity in relationship between the log hazard and the covariates were carefully checked. independent risk factors of aki were assessed using logistic regression. conditional backward stepwise variable selection was performed with . as the critical p-value for entry into the model, and . as the p-value for removal. interactions and correlations between the explanatory variables were carefully checked. influence of outliers, and linearity in relationship between the log hazard and the covariates were carefully checked. it was preplanned to force, one by one, in the final model inflammation biomarker, ferritin, complement pathway dosage and peep level at admission should these variable not be selected. kaplan-meier graphs were used to express the probability of death from inclusion to day . comparisons were performed using the log-rank test. overall, rate of missing data was . % with rate of missing data among major outcome or covariates was < %. as regard to completeness of the dataset, no imputation of missing data was performed. statistical analyses were performed with r statistical software, version . . (available online at https ://www.rproje ct.org/) and the 'survival' package was used. a p value < . was considered significant. overall, covid- patients were admitted in our icu between march and may and included in this study. patients' characteristics are described in table . median age was years [ - ] and patients ( %) were of male gender. only patients ( %) had no underlying disease. hypertension (n = , %), diabetes (n = , %) and chronic kidney disease (n = , %) were the main comorbidities. thirty-six patients were obese (n = , %) or overweight (n = , %) and ( %) were treated with angiotensin converting enzyme inhibitors or angiotensin-receptor blockers. median sofa score at admission was [ ] [ ] [ ] [ ] [ ] [ ] . median modified sofa score [without the renal component] was [ ] [ ] [ ] [ ] [ ] [ ] . fifty-six patients ( %) required mechanical ventilation and ( %) vasopressor therapy. rate of patients with missing baseline serum creatinine was % (n = ) and did not differ between aki and patients without aki ( vs. % respectively; p = . ). aki occurred in patients ( %), including patients, patients, patients with aki stage , and respectively. among patients with aki, ( %) met only urinary output kdigo criteria, ( %) met only creatinine criteria and ( %) met both. urinary output criteria alone was more frequently involved in diagnosis of milder stage of aki (aki stage (n = , %) and stage (n = , %) compared to % in stage (n = , p = . ). thirteen ( %) required renal replacement therapy during the first days in icu. before adjustment, c (p = . ), il- (p = . ) and ferritin levels (p = . ) were associated with aki severity, whereas soluble c b fraction was not different (p = . ) (fig. ) . in a multivariate model incorporating baseline chronic kidney disease, only modified sofa was significantly associated with the development of aki (or per point . ; % ci . - . ). when forced in the final model, c (or per log . ; % ci . - . ), il- (or per log . ; % ci . - . ), ferritin (or per log . ; % ci . - . ), or peep level (or per mmhg . ; % ci . - . ) were not associated with aki and did not change the model. however, after adjustment for modified sofa and ckd, c value higher than median was significantly associated with a lower risk for aki stage or , compared to no aki or aki stage (or . % ci [ . - . ], p = . ), while the association between aki stage or and il- , ferritin, sc b and peep levels did not reach statistical significance (additional file : table s and figure s ). twenty-nine ( %) patients had died by day , ( %) patients with aki and ( %) patient without aki (p = . ). more than half of the patients with aki stage (n = , %) and (n = , %) died before day . the severity of aki was associated with mortality at day (p = . ) (fig. and additional file : figure s ). patients who died were older ( versus years, p = . ), suffered more frequently from chronic kidney disease ( versus %, p = . ), had higher sofa score ( versus , p < . ), ferritin levels ( versus mg/l, p = . ) and il- levels ( versus ng/ ml, p = . ), and were less often immunocompetent ( versus %, p = . ). neither comorbidities nor bmi were associated with death at day . patients who died more often required mechanical ventilation ( versus %, p < . ), vasopressors ( versus %, p < . ) and renal replacement therapy ( versus %, p = . ). after adjustment for confounders, both aki and severity (modified sofa score per point) were associated with survival ( table ) . there was a similar trend towards poorer survival in patients with (n = ) and without (n = ) baseline serum creatinine (additional file : figure s ). we also tested the interaction between missing baseline serum creatinine and reported results and did not find any significant interaction (additional file : table s ). treatments with lopinavir/ritonavir (n = ), tocilizumab (n = ), eculizumab (n = ) or chloroquine (n = ) were associated neither with mortality nor with the development of aki. in this study, we describe the incidence of aki in covid- patients admitted to the icu, and the link between aki, inflammation markers and complement levels. the main results of this case series are the higher than previously reported incidence of aki and its lack of association with il- , ferritin or complement factors c and sc b . the importance of aki in covid- patients has been increasingly recognized. if initial reports from china reported rates of aki as low as . - % in severe patients [ , , ] , incidences from later studies ranged between % [ ] and % [ ] in critically ill patients. most reports lack a clear operational aki definition [ ] [ ] [ ] , but even in studies that used kdigo serum creatinine criteria, diuresis was inconsistently taken into account, and none of them reported aki stages. our study is the largest published to date reporting incidence of aki specifically in critically ill patients. with % of patients diagnosed with aki, the rate of aki in our study is much higher than previously reported. interestingly, one of the largest cohort from the united states reported a prevalence of aki in covid- patients requiring mechanical ventilation of % [ ] , close to our finding of %. one strength of our study is the rigorous use of kdigo criteria, including urinary output. furthermore, given that many patients will present with aki without a reliable baseline serum creatinine on record, estimation of the latter is of tremendous importance. several methods to estimate missing baseline creatinine can lead to variations in incidence of aki up to % [ ] . using complete kdigo definition we found a % incidence of aki during the first days of icu stay and a % incidence in patients requiring mechanical ventilation. we also tested the hypotheses that covid- -associated-aki is linked to the elevation of cytokines induced by sars-cov- infection [ ] , complement dysregulation [ ] induced by sars-cov- infection or mechanical ventilation settings. high levels of il- have been associated with the development of severe disease [ , ] and acute respiratory distress syndrome [ ] during covid- infection, but the role of inflammation markers in covid- -induced-aki remains speculative [ ] . the deleterious role of il- has been demonstrated in different models of aki, including ischemic aki, nephrotoxin-induced aki and sepsis-induced aki [ , ] . in our study, il- and ferritin levels correlated with severity but were not independently associated with aki. the complement system represents the first response of the host immune system. it participates in the development of aki [ ] and has also been suspected to play a role in aki in the context of sars-cov- infection [ , ] . recent studies showed a strong immunohistochemical staining of complement cascade components in the lungs [ ] and kidneys [ ] of severe covid- patients. however, even if c levels were associated with aki severity in univariate analysis, the association did not persist when forced into a multivariate model, and soluble c b showed no association with aki. c level was only independently associated with aki stage and compared to no aki or aki stage . overall, our results do not support a role for complement dysregulation in covid- -induced-aki, even though complement dysregulation may be involved in the most severe forms of aki. although our study did not include extensive coagulation explorations [ ] , the lack of difference in fibrinogen levels in patients with aki when compared to patients without aki does not support the evidence of a role of hypercoagulability in covid- -induced-aki, suggested by the presence of thrombi in glomerular loops described by others [ , ] . last, high levels of peep in covid- patients [ , ] have also been suggested as a potential factor for increased aki in severe covid- patients [ ] . in our study, peep levels were not independently associated with the development of aki, but the lack of statistical power and longitudinal data on peep levels does not allow for any definite conclusion. our study also has limitations. first, despite being the largest focusing on covid- -induced-aki in the icu, the limited number of patients can translate into a lack of statistical power. nevertheless, rate of aki and sample size allow confirming a high aki incidence with a reasonable level of confidence ( %; % ci - ). in addition, the monocenter design may have limited external validity of our findings. the proportion of missing baseline serum creatinine value ( %) may also be an issue. missing baseline creatinine value is a common problem in research focusing on aki, and although most studies do not report the proportion of missing baseline values, rates as high as % are common [ ] . we provide sensitivity analyses (additional file : figure s and table s ) to show that back calculation of missing baseline creatinine values unlikely results in a significant bias. last, lack of association between inflammation biomarker, il- or complement component do 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emmanuelle; appert, alexandra; hadj, mathilde; claverie, paul; matt, morgan; barraud, olivier; françois, bruno; jamoussi, amira; jazia, amira ben; marhbène, takoua; lakhdhar, dhouha; khelil, jalila ben; besbes, mohamed; goutay, julien; blazejewski, caroline; joly-durand, isabelle; pirlet, isabelle; weillaert, marie pierre; beague, sebastien; aziz, soufi; hafiane, reda; hattabi, khalid; bouhouri, mohamed aziz; hammoudi, driss; fadil, abdelaziz; harrar, rachid al; zerouali, khalid; medhioub, fatma kaaniche; allela, rania; algia, najla ben; cherif, samar; slaoui, mohamed taoufik; boubia, souhail; hafiani, y.; khaoudi, a.; cherkab, r.; elallam, w.; elkettani, c.; barrou, l.; ridaii, m.; mehdi, rihi el; schimpf, caroline; mizrahi, assaf; pilmis, benoît; le monnier, alban; tiercelet, kelly; cherin, mélanie; bruel, cédric; philippart, francois; bailly, sébastien; lucet, jc; lepape, alain; l’hériteau, françois; aupée, martine; bervas, caroline; boussat, sandrine; berger-carbonne, anne; machut, anaïs; savey, anne; timsit, jean-françois; razazi, keyvan; rosman, jérémy; de prost, nicolas; carteaux, guillaume; jansen, chloe; decousser, jean winoc; brun-buisson, christian; dessap, armand mekontso; m’rad, aymen; ouali, zouhour; barghouth, manel; kouatchet, achille; mahieu, rafael; weiss, emmanuel; schnell, david; zahar, jean-ralph; artiguenave, margaux; sophie, paktoris-papine; espinasse, florence; sayed, faten el; dinh, aurélien; charron, cyril; geri, guillaume; vieillard-baron, antoine; repessé, xavier; kallel, hatem; mayence, claire; houcke, stéphanie; guegueniat, pascal; hommel, didier; dhifaoui, kaouther; hajjej, zied; fatnassi, amira; sellami, walid; labbene, iheb; ferjani, mustapha; dachraoui, fahmi; nakkaa, sabrine; m’ghirbi, abdelwaheb; adhieb, ali; braiek, dhouha ben; hraiech, kmar; ousji, ali; ouanes, islem; zaineb, hammouda; abdallah, saousen ben; ouanes-besbes, lamia; abroug, fekri; klein, simon; miquet, mattéo; thouret, jean-marc; peigne, vincent; daban, jean-louis; boutonnet, mathieu; lenoir, bernard; merhbene, takoua; derreumaux, celine; seguin, thierry; conil, jean-marie; kelway, charlotte; blasco, valery; nafati, cyril; harti, karim; reydellet, laurent; albanese, jacques; aicha, narjess ben; meddeb, khaoula; khedher, ahmed; ayachi, jihene; fraj, nesrine; sma, nesrine; chouchene, imed; boussarsar, mohamed; yedder, soumaya ben; samoud, walid; radhouene, bousselmi; mariem, bousselmi; ammar, asma; cheikh, asma ben; lakhal, hend ben; khelfa, messaouda; hamdaoui, yamina; bouafia, nabiha; trampont, timothée; daix, thomas; legarçon, vincent; karam, henri hani; pichon, nicolas; essafi, fatma; foudhaili, nasreddine; thabet, hafedh; blel, youssef; brahmi, nozha; ezzouine, hanane; kerrous, mahmoud; haoui, saad el; ahdil, soufiane; benslama, abdellatif; abidi, khalid; dendane, tarek; oussama, ssouni; belayachi, jihane; madani, naoufal; abouqal, redouane; zeggwagh, amine ali; ghadhoune, hatem; chaari, anis; jihene, guissouma; allouche, hend; trabelsi, insaf; brahmi, habib; samet, mohamed; ghord, hatem el; habiba, ben sik ali; hajer, nouira; tilouch, najla; yaakoubi, sondes; jaoued, oussama; gharbi, rim; hassen, mohamed fekih; elatrous, souheil; arcizet, julien; leroy, bertrand; abdulmalack, caroline; renzullo, catherine; hamet, maël; doise, jean-marc; coutet, jérôme; cheikh, chaigar mohammed; quechar, zakaria; joris, magalie; beauport, dimitri titeca; kontar, loay; lebon, delphine; gruson, bérengère; slama, michel; marolleau, jean-pierre; maizel, julien; gorham, julie; ameye, lieveke; berghmans, thierry; paesmans, marianne; sculier, jean-paul; meert, anne-pascale; guillot, max; ledoux, marie-pierre; braun, thierry; maestraggi, quentin; michard, baptiste; castelain, vincent; herbrecht, raoul; schneider, francis; couffin, severine; lobo, david; mongardon, nicolas; dhonneur, gilles; mounier, roman; le borgne, pierrick; couraud, sophie; herbrecht, jean-etienne; boivin, alexandra; lefebvre, françois; bilbault, pascal; zelmat, setti-aouicha; batouche, djamila-djahida; mazour, fatima; chaffi, belkacem; benatta, nadia; sik, ali habiba; talik, i.; perrier, maxime; gouteix, eliane; koubi, claude; escavy, annabelle; guilbaut, victoria; fosse, jean-philippe; jazia, rahma ben; abdelghani, ahmed; cungi, pierre-julien; bordes, julien; nguyen, cédric; pierrou, candice; cruc, maximilien; benois, alain; duprez, frédéric; bonus, thierry; cuvelier, grégory; ollieuz, sandra; machayekhi, sharam; paciorkowski, frédéric; reychler, gregory; coudroy, remi; thille, arnaud w.; drouot, xavier; diaz, véronique; meurice, jean-claude; robert, rené; turki, olfa; ben, hmida chokri; assefi, mona; deransy, romain; brisson, hélène; monsel, antoine; conti, filomena; scatton, olivier; langeron, olivier; ghezala, hassen ben; snouda, salah; ben, chiekh imen; kaddour, moez; armel, anwar; youness, lafrikh; abdelhak, bensaid; youssef, miloudi; najib, al harrar; mustapha, amouzoun; noufel, mtioui; mohamed, zamd; salma, el khayat; ghizlane, medkouri; mohamed, benghanam; benyounes, ramdani; montini, florent; moschietto, sébastien; gregoire, emilien; claisse, guillaume; guiot, julien; morimont, philippe; krzesinski, jean-marie; mariat, christophe; lambermont, bernard; cavalier, etienne; delanaye, pierre; benbernou, soumia; ilies, sofiane; azza, abdelkader; bouyacoub, khalida; louail, meriem; mokhtari-djebli, houria; arrestier, romain; daviaud, fabrice; francois, xavier laborne; brocas, elsa; choukroun, gérald; peñuelas, oscar; lorente, josé-angel; cardinal-fernandez, pablo; rodriguez, josé-maria; aramburu, josé-antonio; esteban, andres; frutos-vivar, fernando; bitker, laurent; costes, nicolas; le bars, didier; lavenne, franck; devouassoux, mojgan; richard, jean-christophe; mechati, malika; gainnier, marc; papazian, laurent; guervilly, christophe; garnero, aude; arnal, jean michel; roze, hadrien; richard, jean christophe; repusseau, benjamin; dewitte, antoine; joannes-boyau, olivier; ouattara, alexandre; harbouze, nadia; amine, a. m.; olandzobo, a. g.; herbland, alexandre; richard, marie; girard, nicolas; lambron, lucile; lesieur, olivier; wainschtein, sarah; hubert, sidonie; hugues, albane; tran, marc; bouillard, philippe; loteanu, vlad; leloup, maxime; laurent, alexandra; lheureux, florent; prestifilippo, alessia; cruz, martin delgado maria; romain, rigal; antonelli, massimo; blanch, torra lluis; bonnetain, franck; grazzia-bocci, maria; mancebo, jordi; samain, emmanuel; paul, hebert; capellier, gilles; zavgorodniaia, taissa; soichot, marion; malissin, isabelle; voicu, sebastian; garçon, pierre; goury, antoine; kerdjana, lamia; deye, nicolas; bourgogne, emmanuel; megarbane, bruno; mejri, olfa; hmida, marwa ben; tannous, salma; chevillard, lucie; labat, laurence; risede, patricia; fredj, hana; léger, maxime; brunet, marion; le roux, gaël; boels, david; lerolle, nicolas; farah, souaad; amiel-niemann, hélène; kubis, nathalie; declèves, xavier; peyraux, nicoals; baud, frederic; serafini, micaela; alvarez, jean-claude; heinzelman, annette; jozwiak, mathieu; millasseau, sandrine; teboul, jean-louis; alphonsine, jean-emmanuel; depret, françois; richard, nathalie; attal, pierre; richard, christian; monnet, xavier; chemla, denis; jerbi, salma; khedhiri, wafa; necib, hatem; scarfo, paolo; chevalier, charles; piagnerelli, michael; lafont, alexandre; galy, antoine; mancia, claire; zerhouni, amel; tabeliouna, kheira; gaja, ali; hamrouni, bassem; malouch, abir; fourati, sami; messaoud, rihab; zarrouki, youssef; ziadi, amra; rhezali, manal; zouizra, zahira; boumzebra, drissi; samkaoui, mohamed abdennasser; brunet, jennifer; canoville, bertrand; verrier, pierre; ivascau, calin; seguin, amélie; valette, xavier; du cheyron, damien; daubin, cedric; bougouin, wulfran; aissaoui, nadia; lamhaut, lionel; jost, daniel; maupain, carole; beganton, frankie; bouglé, adrien; dumas, florence; marijon, eloi; jouven, xavier; cariou, alain; poirson, florent; chaput, ulriikka; beeken, thomas; maxime, leclerc; haikel, oueslati; vodovar, dominique; chelly, jonathan; marteau, philippe; chocron, richard; juvin, philippe; loeb, thomas; adnet, frederic; lecarpentier, eric; riviere, antoine; de cagny, bertand; soupison, thierry; privat, elodie; escutnaire, joséphine; dumont, cyrielle; baert, valentine; vilhelm, christian; hubert, hervé; leteurtre, stéphane; fresco, marion; bubenheim, michael; beduneau, gaetan; carpentier, dorothée; grange, steven; artaud-macari, elise; misset, benoit; tamion, fabienne; girault, christophe; dumas, guillaume; chevret, sylvie; lemiale, virginie; mokart, djamel; mayaux, julien; pène, frédéric; nyunga, martine; perez, pierre; moreau, anne-sophie; bruneel, fabrice; vincent, françois; klouche, kada; reignier, jean; rabbat, antoine; azoulay, elie; frat, jean-pierre; ragot, stéphanie; constantin, jean-michel; prat, gwenael; mercat, alain; boulain, thierry; demoule, alexandre; devaquet, jérôme; nseir, saad; charpentier, julien; argaud, laurent; beuret, pascal; ricard, jean-damien; teiten, christelle; marjanovic, nicolas; palamin, nicola; l’her, erwan; bailly, arthur; boisramé-helms, julie; champigneulle, benoit; kamel, toufik; mercier, emmanuelle; le thuaut, aurélie; lascarrou, jean-baptiste; rolle, amélie; de jong, audrey; chanques, gérald; jaber, samir; hariri, geoffroy; baudel, jean-luc; dubée, vincent; preda, gabriel; bourcier, simon; joffre, jeremie; bigé, naïke; ait-oufella, hafid; maury, eric; mater, houda; merdji, hamid; grimaldi, david; rousseau, christophe; mira, jean-paul; chiche, jean-daniel; sedghiani, ines; benabderrahim, a.; hamdi, dhekra; jendoubi, asma; cherif, mohamed ali; hechmi, youssef zied el; zouheir, jerbi; bagate, françois; bousselmi, radhwen; schortgen, frédérique; asfar, pierre; guérot, emmanuel; fabien, grelon; anguel, nadia; sigismond, lasocki; matthieu, henry-lagarrigue; gonzalez, frédéric; françois, legay; guitton, christophe; schenck, maleka; jean-marc, doise; dreyfuss, didier; radermacher, peter; frère, antoine; martin-lefèvre, laurent; colin, gwenhaël; fiancette, maud; henry-laguarrigue, matthieu; lacherade, jean-claude; lebert, christine; vinatier, isabelle; yehia, aihem; joret, aurélie; menunier-beillard, nicolas; benzekri-lefevre, dalila; desachy, arnaud; bellec, fréderic; plantefève, gaëtan; quenot, jean-pierre; meziani, ferhat; tavernier, elsa; ehrmann, stephan; chudeau, nicolas; raveau, tommy; moal, valérie; houillier, pascal; rouve, emmanuelle; lakhal, karim; gandonnière, charlotte salmon; jouan, youenn; bodet-contentin, laetitia; balmier, adrien; messika, jonathan; de montmollin, etienne; pouyet, victorine; sztrymf, benjamin; thiagarajah, abirami; roux, damien; de chambrun, marc pineton; luyt, charles-edouard; beloncle, françois; zapella, nathalie; ledochowsky, stanislas; terzi, nicolas; mazou, jean-marc; sonneville, romain; paulus, sylvie; fedun, yannick; landais, mickael; raphalen, jean-herlé; combes, alain; amoura, zahir; jacquemin, aemilia; guerrero, felipe; marcheix, bertrand; hernandez, nicolas; fourcade, olivier; georges, bernard; delmas, clément; makoudi, sarah; genton, audrey; bernard, rémy; lebreton, guillaume; amour, julien; mazet, charlotte; bounes, fanny; murat, gurbuz; cronier, laure; robin, guillaume; biendel, caroline; silva, stein; boubeche, samia; abriou, caroline; wurtz, véronique; scherrer, vincent; rey, nathalie; gastaldi, gioia; veber, benoit; doguet, fabien; gay, arnaud; dureuil, bertrand; besnier, emmanuel; rouget, antoine; gantois, guillaume; magalhaes, eric; wanono, ruben; smonig, roland; lermuzeaux, mathilde; lebut, jordane; olivier, andremont; dupuis, claire; radjou, aguila; mourvillier, bruno; neuville, mathilde; d’ortho, marie pia; bouadma, lila; rouvel-tallec, anny; rudler, marika; weiss, nicolas; perlbarg, vincent; galanaud, damien; thabut, dominique; rachdi, emna; mhamdi, ghada; trifi, ahlem; abdelmalek, rim; abdellatif, sami; daly, foued; nasri, rochdi; tiouiri, hanene; lakhal, salah ben; rousseau, geoffroy; asmolov, romain; grammatico-guillon, leslie; auvet, adrien; laribi, said; garot, denis; dequin, pierre françois; guillon, antoine; fergé, jean-louis; abgrall, gwénolé; hinault, ronan; vally, shazima; roze, benoit; chaplain, agathe; chabartier, cyrille; savidan, anne-charlotte; marie, sabia; cabie, andre; resiere, dabor; valentino, ruddy; mehdaoui, hossein; benarous, lucas; soda-diop, marième; bouzana, fouad; perrin, gilles; bourenne, jeremy; eon, béatrice; lambert, dominique; trebuchon, agnes; poncelet, géraldine; le bourgeois, fleur; michael, levy; camille, guillot; naudin, jérôme; deho, anna; dauger, stéphane; sauthier, michaël; bergeron-gallant, krystale; emeriaud, guillaume; jouvet, philippe; tiebergien, nicolas; jacquet-lagrèze, matthias; fellahi, jean-luc; baudin, florent; essouri, sandrine; javouhey, etienne; guérin, claude; lampin, marie; mamouri, ouardia; devos, patrick; karaca-altintas, yasemin; vinchon, matthieu; brossier, david; eltaani, redha; teyssedre, sonia; sabine, meyet; bouchut, jean-christophe; peguet, olivier; petitdemange, lucie; guilbert, anne sophie; aoul, nabil tabet; addou, zakaria; aouffen, nabil; anas, benqqa; kalouch, samira; yaqini, khalid; chlilek, aziz; abdou, rchi; gravellier, perrine; chantreuil, julie; travers, nadine; listrat, antoine; le reun, claire; favrais, geraldine; coppere, zoe; blanot, stéphane; montmayeur, juliette; bronchard, régis; rolando, stephane; orliaguet, gilles; leger, pierre-louis; rambaud, jérôme; thueux, emilie; de larrard, alexandra; berthelot, véronique; denot, julien; reymond, marie; amblard, alain; morin-zorman, sarah; lengliné, etienne; pichereau, claire; mariotte, eric; emmanuel, canet; poujade, julien; trumpff, guillaume; janssen-langenstein, ralf; harlay, marie-line; zaid, noorah; ait-ammar, nawel; bonnal, christine; merle, jean-claude; botterel, francoise; levesque, eric; riad, zakaria; mezidi, mehdi; yonis, hodane; aublanc, mylène; perinel-ragey, sophie; lissonde, floriane; louf-durier, aurore; tapponnier, romain; louis, bruno; forel, jean-marie; bisbal, magali; lehingue, samuel; rambaud, romain; adda, mélanie; hraiech, sami; marchi, elisa; roch, antoine; guerin, vincent; rozencwajg, sacha; schmidt, matthieu; hekimian, guillaume; bréchot, nicolas; trouillet, jean louis; besset, sébastien; franchineau, guillaume; nieszkowska, ania; pascal, leprince; loiselle, maud; sarah, chemam; laurence, dangers; guillemette, thomas; jacquens, alice; kerever, sebastien; guidet, bertrand; aegerter, philippe; das, vincent; fartoukh, muriel; hayon, jan; desmard, mathieu; fulgencio, jean-pierre; zuber, benjamin; soufi, a.; khaleq, k.; hamoudi, d.; garret, charlotte; peron, matthieu; coron, emmanuel; bretonnière, cédric; audureau, etienne; audrey, winters; christophe, duvoux; christian, jacquelinet; daniel, azoulay; cyrille, feray; aissaoui, wissal; rghioui, kawtar; haddad, wafae; barrou, houcine; carteaux-taeib, anna; lupinacci, renato; manceau, gilles; jeune, florence; tresallet, christophe; habacha, sahar; fathallah, ines; zoubli, aymen; aloui, rafaa; kouraichi, nadia; jouet, emilie; badin, julie; fermier, brice; feller, marc; serie, mathieu; pillot, jérôme; marie, william; gisbert-mora, chloé; vinclair, camille; lesbordes, pierre; mathieu, pascal; de brabant, fabienne; muller, emmanuel; robaux, marie-aline; giabicani, mikhael; marchalot, antoine; gelinotte, stéphanie; declercq, pierre louis; eraldi, jean-pierre; bougerol, françois; meunier-beillard, nicolas; devilliers, hervé; rigaud, jean-philippe; verrière, camille; ardisson, fanny; kentish-barnes, nancy; jacq, gwenaëlle; chermak, akli; lautrette, alexandre; legrand, matthieu; soummer, alexis; thiery, guillaume; cottereau, alice; canet, emmanuel; caujolle, marie; allyn, jérôme; valance, dorothée; brulliard, caroline; martinet, olivier; jabot, julien; gallas, thomas; vandroux, david; allou, nicolas; durand, arthur; nevière, rémi; delguste, florian; boulanger, eric; preau, sebastien; martin, ruste; cochet, hélène; ponthus, jean pierre; amilien, virginie; tchir, martial; barsam, elise; ayoub, mohsen; georger, jean francois; guillame, izaute; assaraf, julie; tripon, simona; mallet, maxime; barbara, guilaume; louis, guillaume; gaudry, stéphane; barbarot, nicolas; jamet, angéline; outin, hervé; gibot, sébastien; bollaert, pierre-edouard; holleville, mathilde; legriel, stéphane; chateauneuf, anne laure; cavelot, sébastien; moyer, jean-denis; bedos, jean pierre; merle, philippe; laine, aurelie; natalie, de sa; cornuault, mathieu; libot, jérome; asehnoune, karim; rozec, bertrand; dantal, jacques; videcoq, michel; degroote, thècle; jaillette, emmanuelle; zerimech, farid; malika, balduyck; llitjos, jean-françois; amara, marlène; lacave, guillaume; pangon, béatrice; mavinga, josé; makunza, joseph nsiala; mafuta, m. e.; yanga, yves; eric, amisi; ilunga, jp; kilembe, ma; alby-laurent, fanny; toubiana, julie; mokline, amel; laajili, achraf; amri, helmi; rahmani, imene; mensi, nidhal; gharsallah, lazheri; tlaili, sofiene; gasri, bahija; hammouda, rym; messadi, amen allah; allain, pierre-antoine; gault, nathallie; paugam-burtz, catherine; foucrier, arnaud; chatbri, bassem; bourbiaa, yousra; thabet, lamia; neuschwander, arthur; vincent, looten; beck, jennifer; vibol, chhor; amelie, yavchitz; resche-rigon, matthieu; pirracchio, jean mantzromain; bureau, côme; decavèle, maxens; campion, sébastien; ainsouya, roukia; niérat, marie-cécile; prodanovic, hélène; raux, mathieu; similowski, thomas; dubé, bruno-pierre; demiri, suela; dres, martin; may, faten; quintard, hervé; kounis, ilias; saliba, faouzi; andré, stephane; boudon, marc; ichai, philippe; younes, aline; nakad, lionel; coilly, audrey; antonini, teresa; sobesky, rodolphe; de martin, eleonora; samuel, didier; hubert, noemie; nay, mai-anh; auchabie, johann; giraudeau, bruno; jean, reignier; darmon, michaël; ruckly, stephane; garrouste-orgeas, maïté; gratia, elisabeth; goldgran-toledano, dany; jamali, samir; dumenil, anne sylvie; schwebel, carole; brisard, laurent; bizouarn, philippe; lepoivre, thierry; nicolet, johanna; rigal, jean christophe; roussel, jean christian; cheurfa, cherifa; abily, julien; lescot, thomas; page, isaline; warnier, stéphanie; nys, monique; rousseau, anne-françoise; damas, pierre; uhel, fabrice; lesouhaitier, mathieu; grégoire, murielle; gaudriot, baptiste; gacouin, arnaud; le tulzo, yves; flecher, erwan; tarte, karin; tadié, jean-marc; georges, quentin; soares, m.; jeon, kyeongman; oeyen, sandra; rhee, chin kook; gruber, pascale; ostermann, marlies; hill, quentin; depuydt, peter; ferra, christelle; muller, alice; aurelie, bourmaud; niles, christopher; herbert, fabien; pied, sylviane; loridant, séverine; françois, nadine; bignon, anne; sendid, boualem; lemaitre, caroline; dupre, celine; zayene, aymen; portier, lucie; de freitas caires, nathalie; lassalle, philippe; le neindre, aymeric; selot, pascal; ferreiro, daniel; bonarek, maria; henriot, stépahen; rodriguez, julie; taddei, mara; di bari, mauro; hickmann, cheryl; castanares-zapatero, diego; deldicque, louise; van den bergh, peter; caty, gilles; roeseler, jean; francaux, marc; laterre, pierre-françois; dupuis, bastien; machayeckhi, sharam; sarfati, celine; moore, alex; mendialdua, paula; rodet, emilie; pilorge, catherine; stephan, francois; rezaiguia-delclaux, saida; dugernier, jonathan; hesse, michel; jumetz, thibaud; bialais, emilie; depoortere, virginie; michotte, jean bernard; wittebole, xavier; jamar, françois title: proceedings of réanimation , the french intensive care society international congress date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: a pviol nan introduction the study of the bacterial cartography in thoracic surgery is extremely important for the treatment of post-operative infections due to the severity of the underlying pathology, the fragility of patients after surgery in addition to the choice of the empiric antibiotic therapy. we led a prospective study following all the patients who underwent a pulmonary resection surgery for a period of months from january to july , jointly with the microbiology department, chu ibn rochd, casablanca. the bronchial secretions were collected by a protected distal bronchial sample using a (combicath) after the intubation. results during the period of the study, patients underwent a pulmonary resection, % for a neoplastic pathology. the medium age was years ± and % of our sample were male. % of our patients had smoking habits and of them had pulmonary tuberculosis, had repeated respiratory infections. the antibiotics used in pre-operative: % of beta-lactams; % of fluoroquinolones; % of macrolides. moreover, % of our patients were classified asa . of the obtained samples, were positive ( . %). the most frequently observed germs were the acinetobacter baumannii ( . %), pseudomonas aeruginosa ( . %), klebsiella pneumoniae ( . %), staphylococcus aureus ( . %). the acinetobacter baumannii was the most resistant germ ( % sensibility to carbapenem). these patients were followed until their d after surgery, of them developed a post-operative pneumonitis with cases of multi-resistant acinetobacter baumanii, of which deceased. conclusion pneumonitis after pulmonary resection are common and severe that's why it is necessary to establish a global prevention strategy mainly based on general patricians and pneumologists' awareness concerning the choice of the prescribed antibiotics, in order to avoid the spread of multi-resistant germs. introduction carbapenemase-producing enterobacteriaceae (cpec) are increasingly reported worldwide and constitutes a real challenge antibiotic for clinicians to preserve the bacterial ecology. its incidence has remarkably increased in our intensive care unit during the last years. the esbl spread has a major consequence in term of antibiotic choices. carbapenem antibiotic are regarded as the most effective treatment. however numbers of authors suggest that alternatives antibiotics (i.e. noncarbapenems) could be used in esbl-pe infections. there are some conflicting data regarding the use of alternatives in case of esbl-pe infections. moreover as far as we know, there are no data in icu. objectives the aim of this study was to describe esbl-pe infections in icu and therapeutic options chosen in these specific situations. patients and methods prospective multicentric observational cohort study conducted in volunteers icu. all consecutive patients hospitalized in icu with esbl-pe infection according to cdc definitions were included. severity of illness was defines according to bone criteria, saps ii and sofa. demographic datas, empirical and definitive antibiotic therapy (et and dt), clinical evolution, and outcome were recorded. in vitro antimicrobial susceptibility testing was performed by the disk diffusion method or the vitek system according to the guidelines of the antibiogram committee of the french microbiologic society. results during the study period patients with esbl-pe infection met eligibility criteria with respectively a median age and saps ii score of ( - ) and ( - ). the median sofa score at first day of antibiotic therapy and icu admission were ( - ) and ( ) ( ) ( ) ( ) ( ) ( ) ( ) respectively. the most frequent site of infection were respiratory tract ( %), urinary tract ( %) and abdominal ( %). the most frequent isolated species were: escherichia coli ( %), klebsiella sp ( %) and enterobacter sp ( %). respectively , and % patients had septic shock, severe sepsis and sepsis according to bone criteria. among esbl-pe, . % were carbapenem and . were blbi sensitive. among the whole population, ( %) patients received a carbapenems as et. ( %) received a dt with carbapenems and ( %) patients received an alternative dt. the most frequent reasons for maintaining carbapenems as dt were: antibiotic susceptibility tests ( % of cases), severity level ( % of cases) immunosuppression ( % of cases). the median length of icu stay after infection was respectively ( - ) and ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days for carbapenems and alternatives dt (p = . ). the d mortality was % for patients with carbapenems dt and % for patients with alternatives dt (p = . ). surprisingly, there were no differences between the groups (carbapenems vs alternatives) in term of severity. conclusion alternatives are frequently used for esbl-pe infections in icu. in our cohort ( %) patients received antibiotics other than carbapenems regardless of the severity. introduction bacterial resistance to antibiotics is a common problem worldwide. in south america, this prevalence is reported to be the highest in the world. however, in french guyana, there is no data on the epidemiology of colonization and infection caused by extended spectrum b-lactamase producing enterobacteriaceae (esbl-pe). we conducted this study to investigate the prevalence of colonization with esbl-pe and subsequent icu acquired infection in french guiana. introduction the implementation of hemofiltration (hf) as a renal replacement therapy in septic shock patients requires the supply of large quantities of replacement solutions. these solutions are either industrially prepared in autoclaved expensive plastic bags (conventional hemofiltration, chf) or continuously provided in unlimited amounts at the dialysis machine directly from the water treatment plant to form the replacing solutions (on-line hemofiltration, olhf).the aim of our study was to evaluate the safety and effectiveness of on-line hemofiltration compared to conventional hemofiltration in septic shock patients. the investigative protocol was approved by the institutional ethics authorities and all patients or their legally authorized representatives provided written informed consent. it was a prospective, randomized, clinical study, including septic shock patients with acute renal failure. patients were randomized to receive either on-line hemofiltration (n = ) or conventional hemofiltration (n = ) for renal replacement therapy during days. hemodynamic monitoring was conducted by conventional devises, including: electrocardiogram and a radial arterial catheter for invasive arterial pressure every h during period study. we collected serum samples also every h (urea, potassium and sodium levels, troponin, hemoglobin, platelets, c-reactive protein and lactates). results the evolution of heart rate (hr), mean arterial pressure (map), biological markers were comparable between the two groups over time except a significant decrease in map in the olhf group compared to chf group only at h (p = . ) and h (p = . ) and a significant decrease in c-reactive protein level in the olhf group at h (p = . ). conclusion on-line hemofiltration seems to be a safe and reliable method of renal replacement therapy in septic shock patients. it may be associated with attenuated pro-inflammatory cytokine profile (c-reactive protein). none. introduction therapeutic plasma exchange (tpe) is crucial for the management of auto-immune diseases like thrombotic thrombocytopenic purpura or myasthenia gravis. tpe is performed either by centrifugation, with specific machines which are not routinely available in icus, or by using specific plasma separation membranes with widely spread in icus hemofiltration machines. regional citrate anticoagulation for tpe is well established with centrifugation but has been seldom described for membrane tpe. we are reporting the experience of our icu in this field. patients and methods retrospective study including all patients who received tpe with citrate regional anticoagulation between and in an -bed icu. tpe is performed solely in the icu in our institution. results patients were included. tpe was required for thrombotic microangiopathy ( patients), vasculitis ( patients), hyperviscosity syndrome ( patients), guillain-barré syndrome ( cases) and others ( patients) . mean saps score was [standard deviation (sd) . ] . tpe were performed, with a mean number of . (sd . ; range - ) tpe per patients. coagulation of the circuit of tpe occurred in ( %) patients. coagulation of the circuit occurred in . % ( / ) of the tpe. minor adverse events have been reported in two patients: one had a rash during the first tpe (no recurrence during the next tpes) and the other had paresthesia during the first two tpes (the calcium infusion was increased and there had been no recurrence during the next tpes). no serious adverse events related to citrate were observed. conclusion regional anticoagulation with citrate allowed us to perform tpe in patients, without significant adverse events. the rate of circuit coagulation was . % per tpe. none. introduction a reduced incidence of membrane thrombosis after injection of anti-thrombin (at) has been reported in septic patients with acquired deficit in at undergoing continuous hemofiltration. as this strategy was routinely performed in our unit until , we investigated its cost-effectiveness. patients and methods data about the use of hemofiltration, the consumption of at and hemofiltration devices during (period with routine use of at) and (period with use of at only if a membrane thrombosis occurred) were extracted from the administrative database of the institution. a decisional tree was built to modelize the impact of at on the consumption of hemofiltration devices and blood products. the decisional tree took into account the probability of membrane thrombosis with and without at and the probability of transfusion after membrane thrombosis. costs were obtained from the pharmacy of the institution (at, hemofiltration devices) and from the literature (blood products). results during , days of hemofiltration were performed, with the use of doses of at ( , €) and hemofiltration devices ( , €) . during , (− %) days of hemofiltration were performed, with the use of (− %) doses of at ( €) and (+ %) hemofiltration devices ( , €) . the mean cost of day of hemofiltration decreased from € to € with the diminution of the use of at. according to the decisional tree, at was almost never cost-effective. the only circumstances associated with a benefit for the use of at was the association of a probability of thrombosis with at inferior to . , of a probability of thrombosis without at equal , of a probability of transfusion after thrombosis equal and a cost of transfusion of €. in these extremely favorable circumstances, at could decrease the daily cost of hemofiltration of . - . €. discussion the model has several limits: the losses of utility related to transfusion and to interruption of hemofiltration due to thrombosis were not taken into account; the cost of at measurement was not estimated; the work load of changing a membrane and of transfusion after membrane thrombosis was not analyzed. conclusion our results suggest that anti-thrombin is not costeffective to reduce the costs of hemofiltration related to membrane thrombosis. none. introduction in intensive care unit (icu), some patients suffering from acute kidney injury need renal replacement therapy (rrt). it requires the circuit anticoagulation, this could be done by a regional citrate method. today, this is a recommended approach for the everyday care, even if the technique isn't widespread yet [ ] . the ionized calcemia dosing through the filter ("post-filter" ionized-calcemia) is used to monitor the technique efficacy, with a target of . - . mmol/l showing a good filter anticoagulation. the objective of our study was the assessment of efficacy and safety of our regional citrate anticoagulation protocol, with a less restrictive post-filter ionized calcemia target ( . - . mmol/l). the main goal was the analysis of the circuit lifespan, considering a lifespan above h, as well as the search of some clinical and biological factors affecting the technique efficacy. moreover, we analyzed the side effects incidence of the protocol (hypernatremia, metabolic alcalosis), and their consequences. the study received the scientific ethical agreement of university hospital of toulouse, and is registered with number - . patients and methods patients, admitted to one of the two university hospital icus of toulouse, needing a continuous rrt method, without any need for systemic heparin anticoagulation, and without severe hepatocellular failure, were included in the study. filters included over a -year period were analyzed. results results show a mean filter lifespan of h, with a lifespan above h for . % of all filters. coagulation was the cessation reason for . % of filters, most of them before h of the filter use. a value of post-filter ionized calcemia at day below . mmol/l was the main factor influencing a filter lifespan above h. an age older than and a saps ii severity score below were other factors conditioning a filter lifespan of more than h. side effects of citrate were rare and didn't have any clinical impact among our patients. discussion these results suggest that citrate used for anticoagulation in rrt could have an additional anti inflammatory effect through the induced hypocalcemia, as well as an energetic gain which could lead to a renal protection against ischemia-reperfusion mechanism [ ] . moreover, these results call into question the need of post-filter ionized calcemia dosing for the monitoring of citrate anticoagulation efficacy, since the method safety is monitored by the total-to-ionized calcium ratio. conclusion during continuous rrt in icu, a regional citrate anticoagulation protocol with a non-restrictive post-filter ionized calcemia target seems to be efficient and could reduce side effects. these results need to be confirmed with a randomised control study. introduction continuous veno-venous haemofiltration (cvvh) is used to treat acute kidney injury in critically ill patients. to optimize its efficiency, cvvh requires effective anticoagulation. systemic anticoagulation with standard heparin, the most used, can lead to major bleeding complications. hemofilters that are able to adsorb heparin molecules on their surface such as an st and oxiris membranes represent an alternative. the objective of this study was to compare these two types of filters in terms of duration, efficiency, dysfunctions and cost. materials and methods from october to may , we conducted a retrospective, observational, and non-interventional study. all patients admitted in the intensive care unit needing cvvh were included. the primary endpoint was the filter lifespan: an st versus oxiris. the secondary endpoint was the filter efficiency (urea reduction ratio: urr). the main analysis did not consider the anticoagulation type. we conducted a subgroup analysis taking into account the use or not of an anticoagulation. results sessions in patients were carried out using filters representing , h of treatment. the mean an st filter lifespan was ± h and ± h for oxiris filters (p > . ). there is no significant difference in terms of duration between the two filters. the subgroup analysis taking into consideration the use or not of anticoagulation did not show any difference either. the mean urr was ± % in the an st group and ± % in the oxiris group (p > . ). concerning the dysfunctions, there were no significant difference between the two filters. one hundred and seventy-six an st filters were used for a total cost of , euros. two hundred and ten oxiris filters were used for a total cost of , euros. conclusion the an st and oxiris lifespans are not significantly different. they were as efficient in terms of blood epuration and had as many dysfunctions. the use of an oxiris filter rather than an an st to extend the circuit's lifespan in the same clinical conditions is not justified considering the extra cost generated. introduction because oliguria is a poor prognostic sign in patients with acute renal failure (arf), diuretics are often used to increase urine output in patients with or at risk of arf. from a pathophysiological point of view there are several reasons to expect that loop diuretics could have a beneficial effect on renal function. however, a review of literature shows that the use of loop diuretics in patients with arf has been associated with inconclusive results despite the theoretical benefits [ ] . to assess the adjunctive effect of diuretics, to alter the progression to kidney injury or failure, in patients at risk for acute renal failure. patients and methods this is a retrospective chart review of consecutive patients who developed arf with oliguria in the intensive care unit. chart abstractors were well trained residents. two chart reviewers (senior intensivists) studied all the charts. an explicit protocol was used to precise all needed definitions. uniform handling of data was ensured especially for conflicting, missing or unknown data. oliguria was defined as urine output lower than . ml/kg/h for at least h. rifle score was assessed before and after urinary output normalisation. therapeutic intervention to optimize pre-renal perfusion was described. mean arterial blood pressure (mbp) before and after therapeutic initiation, oliguria duration, delay from oliguria onset to diuretic administration, delay from diuretic administration to urinary output normalisation were measured. results patients were studied over a years period. ] h. the delay from diuretic administration to urinary output normalization was [ . , ] h. after resumption of diuresis, rifle score was assessed as (patients without risk, %; r, %; i, %; f, % l, zero; e, zero) (fig. ) . increased serum creatinine level, above . fold normal range, was observed only in ( %) patients. conclusion rapid optimization of pre-renal hemodynamic disturbances associated with short delay administration of diuretics could significantly alter the progression to kidney injury or failure in at risk acute renal failure icu patients. the ventilator associated pneumonia (vap) is a common and severe complication of assisted ventilation. it's the leading cause of nosocomial infections in intensive care unit and remain responsible for a high morbidity and mortality because of the emergence of multidrug resistant (mdr) bacterial agent such us acinetobacter baumannii (ab). the aim of this study was to determine the incidence, risk factors and prognosis of ab vap. patients and methods retrospective study extending over a year period (january -january ) that included all patients over patients were divided into two groups: one consisting of patients who developed vap to ab and the second developed vap to another bacterial pathogen. results one hundred and forty patients developed vap. the incidence rate of ab vap was . % with a density of incidence of . per ventilator days. age, male gender, the time between hospitalization and mechanical ventilation and the medical pathology were risk factors for developing ab vap. ab was resistant to ceftazidime in %, to imipenem in %, tobramycin in % and netilmycin in . %, rifampin in % with a sensitivity to colistin in % of cases. the resistance of this germ to imipenem increased from % in to . % in . the evolution of patients with ab vap developed frequently septic shock compared to other patients ( vs . %; p = . ). the ab vap mortality was higher ( vs %; p = . ). conclusion the increasing incidence of multi-drug resistant ab vap is responsible for a high morbidity and mortality. so we need to identify risk factors and to strengthen the means of prevention of hand contamination and cross transmission during invasive procedures. introduction central line associated bloodstream infections (clabsi) are among the serious hospital-acquired infections. the aim of this study is to determine the incidence of clabsi, the pathogens and the risk factors that play a role in the development of bsi among patients followed in a tunisian medical intensive care unit. patients and methods all patients admitted for more than h were included in the study over a -year period in an -bed medical icu. the enrollment was based on clinical and laboratory diagnosis of bsi. blood samples were collected from catheter hub of all patients for culture, followed by identification and antibiotic sensitivity testing of the isolates. was higher compared with the mean rate of clabsi in icu reported by the nnis system surveillance for , which is . / catheter.days [ ] . duration of catheterization, frequent manipulation of catheter, catheter location, catheter type, underlying diseases, suppression of immune system, and types of fluids administered through the catheter are significant risk factors in development of bsis [ ] . in our study both duration of catheterization and number of attempts are independent factors for clabsi. conclusion in a monocenter cohort, clabsi had a moderate density rate but are associated with poor outcome. identifying the risk factors is necessary to find solutions for this major health problem. introduction according to some studies, field-intubated patients have . - times greater risk of ventilator associated pneumonia (vap). endobronchial intubation (ei) can be unrecognized by the physicians and may result in complications such as atelectasis which in turn could increase the risk of vap. the aim of our study was to confirm this hypothesis. patients and methods this monocentric retrospective study included all consecutive patients > years who underwent an out-of-hospital tracheal intubation before their admission to the intensive care unit (icu) between january and december . exclusion criteria were suspected aspiration or pneumonia on admission, patients who died within the first days of icu stay, extubation in less than h and underlying disease making radiological interpretation difficult for vap diagnosis. vap were divided into early onset (< days) and late onset (≥ days) events and were independently diagnosed by two experienced intensivists who had no access to the initial chest x-ray performed to check the position of the tracheal tube, based on the clinical pulmonary infection score. onset of ventilator associated tracheobronchitis (vat) was also noted. inadvertent endobronchial intubation was determined by another independent physician based on the interpretation of admission chest x-ray. results patients were intubated out-of-hospital. of the patients excluded, had an extubation in less than h, were died within the first days, had a suspicion of pneumonia, a suspicion of aspiration and an underlying disease making radiological interpretation difficult. of the patients included, ( . %) had an ei upon admission. no significant difference was observed between the ei and non-ei group for gender, age, saps , comorbidities and diagnostic category (cardiorespiratory arrest, trauma, coma and cardiorespiratory failure). early-onset vap were diagnosed in % in the ei group and in % of non-ei patients (p = . ). adding early onset vat, the respiratory infection rate was % in the ei group and % in the non-ei group (p = . ) (fig. ). late-onset vap were observed in . % in the non-ei group and . % in the ei group, without difference between groups (p = . ). there was no inter-group difference in the duration of ventilation, duration of icu stay and icu mortality. staphyloccocus aureus was the most prevalent pathogen in patients with early-onset vap ( . %, only one strain was methicillin-resistant). conclusion this study found a high rate of inadvertent prehospital endobronchial intubation with a higher incidence of early-onset vap. these results support the implementation of specific procedures to decrease the incidence of ei. introduction ventilator-associated pneumonia (vap) is associated with increased hospital stay and high morbidity and mortality in critically ill patients. the classic dichotomy between early and late onset vap is no longer helpful available. the aims of this study were to determine the incidence of multidrug-resistant pathogens in the first episodes of vap and to assess potential differences in bacterial profiles of subjects with early-onset versus late-onset vap. patients and methods retrospective cohort study over a period of months including all patients who had a first episode of vap confirmed by positive culture. subjects were distributed into groups according to the number of intubation days: early-onset vap (< days) or late-onset vap (≥ days).the primary endpoint was the nature of causative pathogens and their resistance profiles. results sixty patients were included, men and women. the average age was ± years. the igs at admission was . [ ; ] apache [ ; ] . monomicrobial infections were diagnosed in of patients ( %).two different bacteria were isolated in cases ( %). a. baumannii was the most frequently isolated in % (n = ) of patients; followed by p. aeruginosa in % (n = ), enterobacteriaceae in % (n = ) and s. aureus in % (n = ). the isolated bacteria were multidrug-resistant in most cases ( / ). the vap group comprised episodes ( %) of early-onset vap and episodes ( %) of late-onset vap. a. baumannii was isolated in % of early vap (n = ) versus % of late vap (n = ) (p = ns), p. aeruginosa in % of early vap (n = ) versus % of late vap (n = ) (p = ns) and enterobacteriaceae in % of early vap (n = ) versus % of late vap (n = ) (p = ns). for the resistance profile of the different pathogens isolated, there was no difference between early and late onset vap. conclusion according to new data from the literature, there were no microbiological differences in the prevalence of potential multidrugresistant pathogens or in their resistance profiles associated with early-onset versus late-onset vap. the bacterial nosocomial infection is a major cause of morbidity and mortality in burned. the bacterial ecology in an icu has a major impact in terms of morbidity and mortality, particularly in the center of burned or length of stay of patients is increased compared to a general intensive care. we conducted an observational study spread over months in icu for severe burned burnt including any who have spent more than h with nosocomial infection (modified cdc criteria), and in which all biological and bacteriological samples were taken. the different types of infections studied were: skin, urinary, lung and bloodstream infections. they excluded all patients belatedly supported or having stayed in other healthcare facilities. results one hundred twenty ( ) patients showed nosocomial infection during this period. the sex ratio (m/f) was . and the mean age was ± years. bacteremia was present in . % of cases, followed by the urinary tract infection that was present in . % of cases, followed by the cutaneous infection in . % of cases, and last pulmonary infection in % of cases. infection was polymicrobial in . % of cases. the main bacteria identified were: acinetobacter baumanii ( . %) of which % is resistant to imipenem, enterobacteriaceae ( . %), pseudomonas aeruginosa ( %) of which . % is resistant to ceftazidime and . % is resistant to imipenem, enterococcus ( %) and staphylococcus aureus ( . %). conclusion the incidence of nosocomial infection is very high compared to literature. the rate of resistance to common antibiotics is very high. a drastic management of antibiotics in our context, the selection of patients and the frequent use in the operating room for skincare allow a better management of these patients. introduction acinetobacter baumannii (ab) ventilator-associated pneumonia (vap) is common in critically ill patients. the aims of this study were to describing the epidemiological characteristics of ab-vap, to identify risk factors for acquisition and factors predictive of a poor outcome. materials and methods a retrospective-prospective study was conducted at the medical intensive care unit of the university hospital ibn sina, rabat-morocco from january to december . they were included in the study that all patients developed vap with identified germ. for identification of risk factors of acquisition of ab vap, two groups of patients were compared: patients with ab vap versus patients with vap caused by other germs. to identify factors associated with mortality, two other groups were compared: survivors versus died. results patients presented vap among which were caused by acinetobacter baumannii. among isolates of ab, . % were drug susceptible, and . % were multidrug-resistant while % were extensively drug-resistant. they were independent risk factors for acquisition of ab vap in multivariate analysis: the presence of a central venous catheter before the occurrence of vap, duration of prior hospitalization ≥ days and icu duration of stay ≥ days. the mortality rate of ab vap was %. the independent risk factors for poor outcome in multivariate analysis were: duration of antibiotic treatment > days, the reintubation and the presence of a previous hospitalization. discussion our data were similar to those of the literature with a high incidence of vap due to the ab ( %) and a high rate of resistance to this bacterium particularly to carbapenems. however, and compared to the literature, the vap ab were responsible for a death rate much higher ( %). conclusion our data were similar to those of the literature with a high incidence of vap due to the ab ( %) and a high rate of resistance to this bacterium particularly to carbapenems. however, and compared to the literature, the vap ab were responsible for a death rate much higher ( %). introduction ventilator-associated pneumonia (vap) is common in critically-ill patients. in fact, - % of patients requiring invasive mechanical ventilation develop this complication. the onset of vap has been reported to be associated with increased mortality. however, data related to critically-ill elderly patients are scarce. the aim of this study is to assess the prognostic impact of vap in critically-ill elderly patients. patients and methods mono-center, retrospective study conducted from / to / / . all old patients (age ≥ years) requiring mechanical ventilation were included. two groups were compared: patients who developed vap (vap (+) group) and those who did not develop vap (vap (−) group). results during the study period, patients were included. the causes of admission in the intensive care unit (icu) were shock (n = ), acute respiratory failure (n = ) and disturbed level of consciousness (n = ). diabetes mellitus, hypertension and chronic obstructive pulmonary disease were the most common comorbidities ( . , . and . % respectively). mean age was . ± . years. sex-ratio (m/f) was . . mean apache(ii) score was ± . the mean duration of mechanical ventilation was ± days. thirty patients ( . %) developed vap. icu-mortality was significantly higher in the vap (+) group ( vs . %; p = . ). multivariate analysis identified two independent factors predicting icu mortality: shock on admission (or = . , ci % [ . - . ], p < . ) and vap (or = . , ci % [ . - . ], p = . ). conclusion vap is common in critically-ill elderly patients and is associated with worse outcome. therefore, preventing its onset is of paramount importance. increased health-care costs. among pathogens responsible of vap, acinetobacter baumannii which is characterized by its ability to spread in the hospital environment and to acquire resistance leading sometimes to therapeutic impasses is associated with a particularly high mortality reaching - %. objective to describe the epidemiological characteristics of a. baumannii vap, to determine their prognosis and identify factors associated with mortality. patients and methods it is a monocentric observational study conducted over a period of years in a tunisian intensive care unit (icu) including mechanical ventilated patients for more than h with confirmed a. baumannii vap. results one hundred and twenty-three patients were included in the study. a. baumannii was responsible for % of vap in our icu. the vap were late in % of cases. more than % of isolates pathogens were resistant to ticarcillin, piperacillin, piperacillintazobactam, ceftazidime and ciprofloxacin. sixty percent of germs were sensitive to imipenem. resistance to imipenem has increased consistently from % at the beginning of the study to % in . all pathogens were susceptible to colistin. a. baumannii vap was complicated by septic shock in % of cases. the median duration of mechanical ventilation and of icu stay were (iqr: [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and days (iqr: - ) respectively. the use of parenteral nutrition was the only factor associated with the occurrence of a. baumannii vap resistant to imipenem (odds ratio . , % ci [ . - . ], p = . ). icu mortality was %. it was higher in patients with a. baumannii vap resistant to imipenem ( vs %, p > . ). in the multivariate analysis, the age, the use of renal replacement therapy and the occurrence of vap relapse have been identified as factors associated with mortality. conclusion a. baumannii resistance to imipenem became threatening. the use of parenteral nutrition was the only factor associated with the occurrence of a. baumannii vap resistant to imipenem. the choice of empiric antimicrobial for vap caused by this pathogen must take in consideration the epidemiologic data of each country and each icu. a. baumannii vap was associated with high mortality. the age, the use of renal replacement therapy and the occurrence of vap relapse have been identified as predictive of poor outcome. none. admission in intensive care unit for severe adverse drug event: what finding? julien arcizet , bertrand leroy , caroline abdulmalack , catherine renzullo , maël hamet , jean-marc doise , jérôme coutet introduction adverse drug events (ade) remain a serious public health problem. they represent between . and . % of hospital admissions and between . and . % of intensive care unit (icu) admissions. they are defined as any injury related to a drug, and include both adverse drug reactions, expected or not, but also underuse, overuse and misuse, unintended or undesired, preventable or not. indeed, mortality from iatrogenic event would rise between . and . %, whereas these ade that resulted in icu hospitalization could be prevented in . - . % of cases. these unplanned admissions overload icu, limit access to health care for other patients and have serious economic consequences for the health system. it is therefore necessary to study these ade to know their main causes and attempt to find a solution to avoid them. the main objectives of our study were to clinically and pharmaceutically analyze and stratify the different ade leading to hospitalization in our icu. this is a monocentric prospective study, between june to january , in medico-surgery icu. from all admissions, we had included patients admitted in our hospital for involuntary ade (plausible, likely and very likely causal). we had collected clinical aspects (failure mode, igsii score, mortality in icu) and pharmaceutical aspect (number of drug, offending drugs) at daily medical staff meeting. conclusion hospitalizations in icu for ade are still too common despite their preventability for most cases. many patients with known cognitive disorder manage their treatment themselves and this is probably one of the reasons of iatrogenic events. anticoagulants and antiplatelet agents, by side effects, misuse, underuse or overuse are very often involved. the onset of kidney failure from dehydration and the continuation of nephrotoxic and antidiabetic treatment also remain one of the most common causes. consequently, it is necessary to continue and develop primary, secondary and tertiary prevention strategies to prevent their appearance, to limit their consequences and to reduce recidivism. introduction intensive care unit (icu) is usually identified as a place of acute care, concentrated over a short period. for many reasons, a prolonged stay in the icu has a pejorative connotation for the intensivist physician. the aim of our study is to describe the epidemiological, clinical, paraclinical profile of patients hospitalized for a long time in icu (over days) and to identify the main prognostic factors and those that can predict the duration of stay in icu. we conducted a retrospective study, over a period of years and months (january to june ), enrolling patients whose length of stay was greater than or equal to introduction despite an improvement in prognosis of patients with hematologic malignancies for the last decade, mortality of such patients admitted to the intensive care unit (icu) remains high. yet, it seems that a first icu stay does not modify prognosis of the malignancy. until now, there is no data on readmission in the icu of such patients and its effect on short and long term prognosis impact. patients and methods this retrospective, single-center study conducted on a years period in the medical icu from our university hospital included patients with hematological malignancies admitted for a first stay. objectives were to evaluate the icu, day and months mortality, to identify prognostic factors associated with mortality within uni-and multivariate analysis, to evaluate readmission rate within the days after discharge, to indentify the admission risk factors associated with icu readmission and the prognosis factors associated with mortality during the second icu stay. multivariate analysis poor performance status, igs ii, hlh, mv and anti-fungal administration were associated with increased icu mortality, infections with pseudomonas were associated with higher day mortality. catheter related infections were associated with better icu survival and cr was associated with lower day mortality. of ( . %) candidate patients for icu readmission after a first stay were readmitted within the days following discharge. median overall survival was lower in readmitted versus non readmitted patients. months mortality was . % for readmitted versus . % for no readmitted patients (p < . ). the second icu stay mortality was . % and month mortality was . %. by multivariate analysis, only mv was associated with prognosis. the months mortality rate of patients who survived to the second icu stay was significantly higher than the patients who survived to the first admission but were not readmitted ( . vs . %, p = . ). conclusion main features, short and long term mortality and prognostic factors associated with icu admission are in lines with previous studies. early readmission rate was high with a negative impact on survival. despite admission in the icu of patients with hematologic malignancies seems not to affect long term prognosis, early readmission seems to have a pejorative impact on the course of the malignancy. introduction lung cancer is among all types of cancer, the most common solid tumour admitted in intensive care [ ] . recent studies showed that the prognosis of patients with lung cancer during intensive care unit (icu) stay has improved [ ] . the aim of our study was to determine the causes of icu admission of lung cancer patients, their prognosis and to identify factors predicting hospital mortality and survival after hospital discharge. in fact, temporary full-code icu management in patients with relapsed aml seems to be appropriate. none of the life-sustaining interventions at admission and on day were able to predict survival. an icu trial of days might not be enough to appraise precisely the outcome. bone marrow transplant was associated with a high mortality in our study. in case of relapsed aml with bmt, icu management is still challenging. the growing population of chronically critically-ill patients has a poor prognosis despite all the resources mobilised [ ] . our primary objective was to analyse the prognostic value of different definitions used to describe them. our secondary objective was to look for early clinical and biological factors that could be associated with the in-hospital mortality. we conducted an epidemiological prospective study in intensive care units (neurosurgical, cardiosurgical and medical) of a large french teaching hospital (henri mondor, créteil). we included all the patients hospitalized for at least days. we tested definitions: the prolonged mechanical ventilation, the definition taken up by kahn et al. [ ] , the prolonged length of stay, the persistent critical illness and the persistent inflammation-immunosuppression and catabolism syndrome. two biological examinations were performed: upon entering the study and week later. the study endpoint was the in-hospital mortality. results thirty patients were included between april and july . among them, only % matched the definition of prolonged mechanical ventilation, which is still the most used in the literature. further, it was not associated with the mortality, but the prolonged length of stay was, with % of these patients, that did not survive to their hospital stay. other parameters that were significantly different between the patients who died and those who survived were an advanced age, an elevated igs ii score at hospital admission, an elevated sofa score at study entry, a late healthcare-associated infection and several biological variables: a high c reactive protein, low albumin and prealbumin and a poor percent of monocytes expressing hla-dr, all measured at day . conclusion the in-hospital mortality of chronically critically-ill is still high. a prolonged length of stay is the only definition who may be helpful to identify the patients with the poorest outcome. among the early factors associated with mortality, we found a late healthcareassociated infection and a low percent of monocytes expressing hla-dr, pointing to the value of studying the immune system of these patients. introduction as a result of demographic transition, the proportion of «very elderly» (≥ years) patients is increasing worldwide and more of these patients are nowadays admitted to intensive care units (icu). among physicians the discussion about appropriateness of these icu admissions still remains controversial mostly due to questionable outcome, limited resources and costs. the aim of the study was to determine and evaluate the clinical characteristics and outcome in a very old population admitted to a medical icu in an urban teaching hospital. we present here a monocentric, retrospective and observational study. we reviewed the charts of all patients (≥ years) admitted to a medical icu between and ( years). we collected epidemiological, clinical and biological parameters and all therapeutic measures during the icu stay. a longterm survival follow-up was also performed. two hundred eighty-four patients were included for statistical analysis. multivariate cox regression was also performed to identify risk factors for -day outcome. results a total of patients were included, which represented . % of admissions to the icu during the period of the study. the mean age was . ± . years, the sex ratio was . . most of patients ( %) were admitted from the emergency department. % of these admitted patients suffered of previous dementia. the mean charlson comorbidity score was . ± . and the mean mccabe score was . ± . . the admission diagnosis in the icu was mainly respiratory distress ( %), septic shock ( %), cardiac arrest ( %) and coma ( %). the mean saps-ii score within h of icu admission was . ± . . half of these patients required support by mechanical ventilation (mean duration . days) and vasoactive drugs and % of patients received renal replacement. icu and in-hospital mortality rates were and % respectively. overall survival at months after hospital discharge was %. multivariate regression revealed necessity of catecholamines and mechanical ventilation as independent risk factors and urinary sepsis as protective factor for -day outcome. in fine, for % of these patients, a limitation of active treatment was decided (on average after days of stay). for all others there was no justification for limiting care because of a well-established treatment plan (with family, gp, icu team). conclusion the proportion of elderly patients remains low, but they are increasingly being treated in intensive care units. nevertheless, the in-hospital mortality is high compared to the average mortality in our icu over the same period ( %). the prognosis is often not as poor as initially perceived by physicians. the indication for icu treatment in our study was mostly justified; in the setting of consistent patient care and good clinical practice. it remains therefore appropriate to discuss every single icu admission of elderly patients without any restriction related to age. thus, the ongoing cluster-randomized trial of icu admissions for the elderly patients (ice-cub study) is deeply awaited to confirm or not these results [ ] . keywords intensive care; prognosis; outcome; elderly patients; over -years old. introduction regardless of the route of delivery, the postpartum hemorrhage (pph) is defined as blood loss ≥ ml after childbirth, and severe pph as blood loss ≥ ml. pph is the leading cause of maternal mortality in africa. the aim of this prospective study was to assess the quality of the initial management of pph in algeria in oran ehu and to determine the factors of care with the severity of this complication. we conducted a prospective cohort study between april and september at the ehu oran. all women who delivered vaginally and showed hpp including the suspected cause was uterine atony were included. the severe pph was defined as bleeding that required invasive surgical treatment (hysterectomy, arterial ligation), a transfusion, a transfer to an intensive care unit or death of the patient. the quality of care was evaluated using objective criteria defined by a delay of diagnosis and care and mortality. results among the women who delivered vaginally during the study period, had a pph, link with uterine atony alleged at diagnosis, of which presented signs of severity. in % of cases, the delay in diagnosis of pph was less than min; % of women received oxytocin within min after diagnosis. the tranexanique acid was used in case. the examination of the cervix, uterine exploration and uterine massage was performed in , and %, respectively. the failure of first line treatment involved % of patients. among them, the time between the diagnosis of pph and administration of blood derivatives was greater than h in a third of cases. the administration of oxytocin delay exceeds min multiplied by . the risk of severe pph. however we had deaths in our series. discussion in our study the optimal period of care was not adequate, obtaining blood derivatives in our institution remains among the factors aggravating among the main risk factors for pph, uterine atony was the main source of complication. bleeding postpartum aggravated in our two patients has led to the deaths from late diagnosis and care that was not optimal. these hemorrhages pp is the leading cause of mortality: % of obstetric deaths ( % in the confidential survey - ) [ ] . a hysterectomy was indicated after failure to conservative treatment. the death rate is estimated at % following a disorder complicated hemostasis of disseminated intravascular coagulation (dic). in some series, the mortality rate is estimated between and % [ ] . conclusion the management of pph in obstetrics gynecology service the ehu oran was not optimal. the issue of timing of diagnosis and initial treatment is crucial. solutions must be sought locally to ensure the administration of essential medicines in time, especially the injection of oxytocin within min after diagnosis. introduction chronic obstructive pulmonary disease (copd) is a common pathology that would represent the third cause of death worldwide by . its evolution is interspersed with episodes of acute exacerbations (aecopd) that may indicate an admission in intensive care unit in the most. objective to study the evolution of management modalities of patients admitted in our intensive care unit for aecopd, to determine their prognosis and to identify factors associated with mortality. patients and methods it is a retrospective, monocentric study, performed in a tunisian intensive care unit (icu) over a period of years. we including all patients admitted in icu for aecopd. parameters collected were demographic features, comorbidities, regular treatment, dyspnea assessed by the mrc scale, initial clinical severity reflected by saps ii and apache ii scores, modalities and icu admission deadlines, initial arterial blood gas analysis, management of patients in the icu (ventilation modalities, prescription of antibiotics, use of vasoactive drugs) and their outcomes (incidence of nosocomial infections and their sites, length of stay and icu mortality). results a total of patients, which represents . % of all hospitalizations, with mean age of years (iqr: - ) were admitted for aecopd during the study period. the mean saps ii and apache ii were respectively (iqr: - ) and (iqr: - ). of these, % were ventilated with niv whose overall failure rate was % with a significant decrease between the beginning and the end of the study ( vs % p = . ). sixty-four percent of patients received antibiotics at admission. the prescription rate of antibiotics has decreased significantly over the years from to %. the incidence of nosocomial infections was %. it remained steady between and %. their sites were pulmonary in % of cases. icu mortality was %. in multivariate analysis, icu admission deadlines, niv failure and the use of vasoactive drugs were identified as factors associated with mortality. conclusion our study showed the importance of aecopd in the activity of our icu. the management of these patients has evolved over the years, which was reflected by the significant decrease in the prescription of antibiotics and the enhancement of niv success rate. this result could be attributed to the combination of several factors: precocious management of patients, experience of the healthcare team and the use of efficient ventilators. icu admission deadlines, niv failure and the use of vasoactive drugs were identified as factors associated with mortality. introduction aim. investigate the effect of music therapy on the tolerance of non-invasive ventilation (niv) during its introduction. currently, % of the trauma are intubated. thirty-three percent of the patient admitted in intensive care suffers from acute respiratory distress syndrome (ards). the fmhs chose oxygen concentrator as oxygen source in addition to oxygen pressurized bottles. their supply can be uncertain in conflict areas. insufficient data are available concerning the use of oxygen concentrator in intensive care unit. the primary endpoint was to determine over the total duration of oxygen therapy, the number of days on which the use of pressurized oxygen was needed for patients oxygenated by oxygen concentrator. the secondary endpoints were to identify when pressurized oxygen was needed, describe the characteristics of the population with oxygen therapy and estimate the oxygen quantity economised thanks to the use of oxygen concentrator. the study took place in the forward surgical unit of bouffard. it's a french role located in djibouti republic in africa. all patients over admitted in the intensive care and needing oxygen therapy were included. all the patients were oxygenated with an oxygen concentrator. the oxygen concentrators used were sequaltm integra om, that could deliver up to l/min of normobaric oxygen. the ventilator used were pulmonetictm ltv and . results thirty-six patients were included over the months' study period. sixty percent of the patients were men with an average age of two hundred and fifty-one days represents the total number of days of oxygen therapy divided into days of invasive ventilation, days of noninvasive ventilation and days of oxygen mask. the use of pressurized oxygen was necessary times over the days of oxygen therapy which represents . % of the total time. the causes of its use were in ten cases ( . %) criteria of severe ards, in six cases an emergency intubation and in three cases a transfer. one dysfunction of an oxygen concentrator happened during our study. the oxygen concentrator produced m of oxygen over the study period, which represents oxygen pressurized bottles of litres. this enabled an economy of , euros. conclusion it is safe to use oxygen concentrator to take care of critically ill patients in limited resources environment. the use of pressurized oxygen is still compulsory in two situations: in case of electricity failure and in case of high fio (above %). oxygen concentrators are sufficient in . % of the time. they enable to deliver oxygen any time which is essential when supply is uncertain in conflict areas. none. table ). for the same mv and level of ofr, fdo was in our experiment, with an ofr of l/min, when ifr = l/min (mv = l/min and ti/ttot = . ), the fdo is equal to % (± %) (see table ). to this value of ifr, the fdo is in accordance with the formula of ats, but when ifr increase beyond l/min, the fdo decrease and the formula is not in accordance with ats. this can be explain because during inspiratory phase, air room (fractional oxygen = . ) entry in airway mixes with ofr (fo = ), which modifies the fdo . in this case, when ifr increase then fdo decrease and vice versa. medical and paramedical staff must be aware that with patients who receive ofr by nasal cannula, any change of ofr and/or inspiratory flow changes the fdo . in this case, for maintain the same fdo , it is necessary that modify the value of ofr. the actual fio delivered under oxygen mask in patients with acute respiratory failure and the factors that may influence the fio are poorly known. in clinical practice, different methods including formula or conversion tables based on oxygen flow can be used to estimate delivered fio . we aimed to assess first the factors influencing measured values of fio , and second the best method to estimate fio in patients breathing under oxygen mask. we included icu patients admitted for acute hypoxemic respiratory failure from a previous prospective trial [ ] in whom fio was measured under oxygen mask using a portable oxygen analyzer. we collected demographic variables and respiratory parameters that may influence measured fio . low fio was defined according to the median measured fio . for each patient, measured fio was compared to "calc + %" formula (fio = oxygen flow in liters per minute × . + . ) to "calc + %" formula (fio = oxygen flow in liters per minute × . + . ), and to a conversion table [ ] . a ± % limit of agreement for each estimation method was arbitrarily considered acceptable. results among the patients included, median measured fio was % [ - ]. after adjustment on oxygen flow, the three variables independently associated with low measured fio using multivariate analysis were patient's height, a low paco , and a respiratory rate greater than breaths/min. using paired analysis, each estimation methods differed significantly from measured fio (p < . for each). values outside the limits introduction acute hyperglycemia is common in intensive care. it was associated with poor prognosis and increased mortality. the purpose of our study is to investigate the frequency of hyperglycemia in our icu, to determine the main causes of high blood sugar and to analyze the impact of this hyperglycemia. our study is prospective during months. it was conducted in the intensive care unit of the university hospital habib bourguiba sfax-tunisia. were included in our study all patients admitted to the service during the period of the study. for each patient included were collected from the icu admission, clinical and biological data. results during the study period, patients were hospitalized in our icu and the diagnosis of hyperglycemia (> mmol/l) was admitted in patients ( %). the comparison between patients who developed hyperglycemia and those free hyperglycemia group showed that, the patients of the first group were significantly older (p < . ). additionally, hyperglycemic patients had more medical history including history of diabetes (p < . ), a higher saps ii (p < . ), a more significant frequency of active infections (p < . ). moreover, the presence of hyperglycemia was associated with shock (p < . ) and respiratory distress (p < . ). their evolution was marked by the significantly higher frequency of infectious complications (p < . ), thromboembolic complications (p < . ) and acute renal failure (p < . ). the average duration of mechanical ventilation and the length of stay were also significantly prolonged in hyperglycemia group patients (p < . for both). finally, the presence of hyperglycemia was significantly associated with a higher mortality rate. conclusion we concluded that hyperglycemia is correlated with poor prognosis of morbidity and mortality. but strict glycemic control remain controversial. thus, further studies on this subject will be recommended to define the exact place of glycemic control in intensive care. none. the rrt was prophylactic in four cases started when phophatemia was more than mmol/l, and therapeutic for renal failure and established tls in three cases. the median duration stay in icu was [ ] [ ] [ ] [ ] j. thirteen patients left the icu without major metabolic dysfunction. two patients deceased due to infectious complications. discussion monitoring of electrolytes was done on average, three times a day which is hard to do in onco-hematology unit. the early use of rasburicase and the aggressive iv hydration helped to prevent tls for seven patients. the aggressive iv hydration was made according to echocardiography data and close monitoring of vital signs and urine output which has allowed to avoid volume overload and acute pulmonary edema. the early prophylactic rrt prevented renal failure and metabolic complications. conclusion early management of tls in icu can prevent tls and most of its serious complications and should be considered in tls prophylaxis recommendations. none. the both urinary (expressed as the ratio of ngal on urinary creatinine) and plasma ngal were predictive of aki stage . predictive value of plasmatic measurements was higher than the urinary one (auc of . and . , respectively, p = . between auc), but not higher than either baseline serum creatinine (auc = . ) or h diuresis (auc = . ). backward multivariate regression showed that plasma ngal concentration was associated with serum creatinine, crp and albumin, whereas urinary ngal was associated with leucocyturia and baseline creatinine. discussion previous positive studies with ngal did not compare the performance of this costly biomarker with simple usual clinical parameters to predict aki. moreover, several parameters were associated with ngal concentrations with a high risk of collinearity (crp) and/or false positive results (leucocyturia). our data do not support any added value of ngal concentration over baseline serum creatinine or urine output to predict aki. introduction acute renal failure (arf) is a common entity in intensive care, concern that the heavy morbidity and mortality it is associated [ ] . early diagnosis of this entity remains difficult, neither diuresis and creatinine are early parameters in the diagnosis of arf. the kidney is an organ that suffers long to become faulty, the priority is to recognize renal aggression and to achieve a therapeutic allowing reversibility of the infringement. a number of markers have been developed for the diagnosis of the ira but costs remain high not allowing their routine use. the measurement of resistance index with the renal doppler could be a solution for the diagnosis of aggression and also of the etiology. the elevation of creatinine was seen later within h after the ir > . discussion in our series the resistance index has a value of early diagnosis of renal prognosis aggression in the occurrence and development of renal failure. renal doppler associated with a strictly applied standardized protocol achieves the two goals of monitoring who aid in the diagnosis and guide treatment. although the recommendations of experts to this tool provides that it should probably not use the resistance index measured by renal doppler to diagnose or treat an ira (grade ) [ ] . identifying the cause of kidney aggression is a prerequisite before any therapeutic action. hypovolemia and soda hydro overload are the causes principales. excess filling hyper intra thoracic pressure and hypoxia are the main causes of kidney congestion. conclusion doppler is an early renal medium in the diagnosis of renal aggression. a larger series could assert this observation. none. ), had significantly more pre-eclampsia, / ( %) versus / ( %) p = . . pe were started at an average of . days after foetal extraction, and with an average of sessions. patients of the pe group had significantly lower nadir of hemoglobin but also lower hemoglobin level at day and day . nadir of platelets count was also lower and level remain lower at days , , and . acute kidney injury (using kdigo classification) was more frequent with a higher rate of dialysis in icu, in the pe group ( / ( %) vs / ( %) p = . ) with a more frequent need for dialysis at the exit of icu. proteinuria was significantly higher in the pe group ( . mg/mmol vs . mg/mmol, p = . ). adamts dosage was done only in patients with pe. we find a diminution of adamts activity (before pe) with an average of % [ - ] in this group. there was no death, and adverse effects were not significantly different. discussion this study shows that pe was used when diagnosis was uncertain in the most severe form of pp-tma. low hemoglobin, low platelets, acute kidney injury and high level of proteinuria are the main factors associated with the decision to begin pe. this technique was safe and not associated with major adverse events. several studies show that there are physiopathological crossovers between diseases associated with pp-tma, for example low adamts activity in hellp or mutation in alternative complement pathway which induced hellp. moreover, studies and case reports show a benefit of pe in hellp syndrome. our study did not find significant difference in adverse events (maybe due to a lack of power), but this is another argument to discuss pe in the management of pp-tma in severe patients. the main limits of our study are that none of the patients who had a plasmatic exchange had a diagnosis of ptt and that diagnosis tests were not performed in all patients with pp-tma (complements level, adamts …). conclusion pp-tma treated with pe has lower hemoglobin, lower platelets, higher rate of kidney injury and proteinuria than those treated without pe. no difference were found for adverse events. begining of pe should be discussed for management of a pp-tma without amelioration after foetal extraction. none. introduction diffuse alveolar damage (dad) is the typical histological feature of acute respiratory distress syndrome (ards). however, in a previous study including patients with criteria for ards, we found that only % of them had dad at autopsy exanimation [ ] . it has been shown that patients with ards and dad on open lung biopsy had higher mortality than those without dad [ ] . thus, we aimed to identify markers associated with dad in patients with ards. we included the patients who met criteria for ards at time of death in our large database of clinical autopsies [ ] . we assessed the proportion of dad according to the severity of ards including the degree of hypoxemia and the ancillary variables from the berlin definition: use of high levels of positive endexpiratory pressure (peep at least cmh o), radiographic severity ( or quadrants on chest radiograph), altered respiratory system compliance (≤ ml/cmh o), and large dead space defined as a corrected expired volume per minute (≥ l/min). results dad was associated with all the severity markers abovementioned using univariate analysis. after multivariable logistic regression, the three markers independently associated with presence of dad were the gender with an odds ratio ( conclusion dad was significantly more frequent in females. in addition to the severity of hypoxemia, diffuse infiltrates involving the quadrants was a significant marker of dad. introduction ventilation induced lung injury (vili) is responsible for an increased mortality in ards [ ] . mechanical ventilation may trigger an inflammatory response, comprising alveolar macrophage activation and recruitment, which may be specifically, repeatedly and spatially assessed by functional imaging techniques such as positron emission tomography combined with computerized tomography (pet/ct) [ ] . c-pk is a pet radiotracer with potential to quantify macrophage inflammation. we aim to assess its performance to detect lung macrophage recruitment in an experimental highvolume vili model. materials and methods vili was performed in anesthetized pigs under neuromuscular blockade by rapidly increasing the tidal volume (vt) to obtain a transpulmonary pressure (tpp) between and cmh o under zero end-expiratory pressure. pet/ct acquisitions were performed before (t ) and after h of high-volume ventilation (t ), and image-derived measurements were realized on the whole lungs, and regionally on distinct lung regions (divided along the anteroposterior and the cephalocaudal axes). c-pk lung uptake was estimated using the standardized uptake value (suv), normalized to the ct-derived tissue fraction in the region of interest (roi). mechanical lung aggression was estimated by ct-derived dynamic and static strains, and tidal alveolar hyperinflation (expressed as a fraction of the tidal variation in the roi volume). after euthanasia, alveolar damage and macrophage recruitment were assessed in the lung regions, using semi-quantitative scores. results between t and t , vt and tpp significantly increased from . ± . to . ± . ml/kg and . ± . to . ± . cmh o, respectively. suv on the whole lung significantly increased from . ± . to . ± . between t and t and dynamic strain from . ± to . ± . , whereas static strain did not significantly vary. tidal alveolar hyperinflation significantly increased from ± to ± % on the whole lung between t and t . regionally, dynamic strain, and tidal alveolar hyperinflation significantly differed between regions, as well as between t and t . regional suv differed between t and t but not between regions. regional static strain did not differ between regions, nor between t and t . in multivariate analysis, regional suv was independently and significantly associated with dynamic strain and tidal alveolar hyperinflation. histologic analysis showed significant regional differences in alveolar damage but not in macrophage recruitment. suv was positively associated with macrophage recruitment but not with alveolar damage. discussion in this experimental vili model, c-pk suv was significantly increased after h of injurious ventilation, and was significantly and positively associated with high-volume ct-derived mechanical parameters, such as dynamic strain and tidal alveolar hyperinflation. the radiotracer's specificity for macrophages is confirmed by the suv significant association with macrophage recruitment and the lack of association with alveolar inflammatory edema. conclusion c-pk is a macrophage-specific pet radiotracer, with potential to dynamically and specifically assess alveolar macrophage inflammation induced by high-volume ventilation. research founded by the french society of intensive care medicine (srlf) and la fondation pour la recherche médicale (dea ). the reverse triggering (rt) is the term used to name the contractions reflexes of the muscle diaphragmatic provoked ("triggered") by the periodic insufflations, delivered by the ventilator, at sedated patients under mechanical ventilation [ ] . the rt constitutes a new form of patient-ventilator interaction clinically difficult to detect and little known. the rt could have potential implications during the management of acute respiratory distress syndrome (ards). at present, the management of severe ards consists among others, on the use of an early and systematic perfusion of neuromuscular blockade agents (nmba) during a h' period, continuation to the acurasys essay which showed a reduction of the mortality in the group of the severe ards patient receiving nmba. the reason of the beneficial effect of curare is not perfectly known. it is possible that the phenomenon of rt is a mechanism implied in the deleterious role of the mechanical ventilation during ards. the abolition of this phenomenon by nmba could explain the beneficial effect of nmba in ards [ ] . the objective was to look for the phenomenon of rt in two groups of ards patients: a group receiving nmba and a group not receiving nmba. patients and methods physiological observational and comparative study in intensive care units. we record continuous signals of airflow, airway pressure, and esophageal pressure during h of consecutives patients with ards criteria and pao /fio ratio ≤ at a positive end-expiratory pressure (peep) of cmh o evolving for less than h under mechanical ventilation. recording of esophageal pressure of consecutives moderate to severe ards patients were blinded analyzed (group nmba n = ; group unless nmba n = ). any phenomenon of rt was observed in the group of mild ards patients receiving nmba (fig. a) . we confirmed the existence of rt on patients of in the group of mild ards who not receiving nmba (p = . ) (fig b) . discussion one of the main limits was the quality of the collection of the signal of esophageal pressure. the monitoring of esophageal pressure is technically difficult, and can d influence the quality of the signal and the reliability of the results. conclusion this study confirms the existence of the phenomenon of reverse triggering among deeply sedated patients not receiving nmba with a % incidence. more research is needed to determine if the reverse triggering is a risk factor independent from vili, associated with the bad prognosis of severe sdra patients and, if a strategy of early treatment based on nmba, could improve the prognosis of reached patients. after ecmo removal had a significant median reduction of days in the bipap-aprv group, p = . (fig. ). we reported the feasibility of a protocol based on bipap-aprv aiming at resuming sv as soon as possible in ards patients under ecmo. the occurrence of spontaneous inspiratory efforts in ards patients can major variability of transpulmonary pressure and as result jeopardise vt and driving pressure control. this might be an issue if protective ventilation is not guaranteed anymore. vt with bipap-aprv remains within safe range when the ratio fig. circles are pac group, rhombus are aprv group. mv mechanical ventilation, psv pressure support ventilation. data are presented as median (iqr), comparison between the groups at each time mann-whithney test, *p < . of spontaneous minute ventilation to total minute ventilation is between and % [ ] . bipap-aprv is more efficient than psv to increase lung aeration in patients with ards [ ] . recruitment of dependent region is more likely to achieve if sv is not supported by synchronized positive airway pressure as during bipap-aprv [ ] . our strategy targeting a percentage of sv between and % with high peep could be viewed as a compromise in order to promote sv and protective ventilation at the same time. conclusion protective ventilation combined with sv under ecmo by using a specific protocol based on bipap-aprv is feasible and safe. it may facilitate weaning and thus reduce the time under mv after ecmo. to what extend this beneficial effect is directly due to the presence of sv deserve further investigations. introduction since the first transplant from a patient in a state of brain death conducted in at the university teaching hospital ibn rushd of casablanca, the number of transplants has increased. however, it is still inadequate meet the growing needs of organs. the refusal of families remains the main obstacle to the developpement of organ transplantation in morocco. the aim of our study is to monitor and analyse the evolution of family refusal to organ donation in a brain dead patient. patients and methods this is a retrospective and comparative study from august until december .the data were collected from records of brain dead patients candidates for organ donation at the intensive care units on ibn rushed hospital. the coordination registers were also studied. a questionnaire was distributed to families who refused organ donation to investigate the causes of the refusal. results during this period, patients with brain death have been identified and families had been approached. families ( %) refused organ donation. the main causes of refusal were: fear of body mutilation ( %), lack of will ( %) and religious causes in % of cases. the refusal rate for families decreased from % in to % in . only patients experienced cardiac arrest before transplantation. during this period, cornea transplants from braindead patient were conducted with kidney transplants and two liver transplants. discussion the evolution of the refusal of families saw a decline through awareness and communication campaigns for organ donation. conclusion improvements to our health care system must be proposed including strengthening detection of potential donors and relationships with the donor's family and effective communication policy. in the icu, three major actors are involved in the caring relationship: patient, relatives and caregivers. acting as spontaneous testimonials of the lived experience, thank-you letters from relatives may be considered by icu teams as a source of original information which could help in improving care for critically ill patients and families. this study aimed to investigate the qualitative content of thank-you letters from relatives of patients who stayed in the icu. specifically, our research questions were, with regards to the letters' content, ( ) how is the caring relationship tackled and characterized by relatives? ( ) to what extent does this relationship impact their experience of icu? materials and methods the study took place in a -beds icu during a -month period. the research team consisted in a care assistant, a nurse (also clinical research associate), a psychologist (not working in the icu) and an intensivist. the corpus consisted in twenty thankyou letters received in the icu. we conducted a qualitative study according to the thematic inductive approach. the process of coding was intended to create established meaningful patterns. results two main themes emerged as specific determinants of the caring relationship: ( ) the temporality, comprising the time dedicated to the patients and their family, the time spent with the icu team, the striking time corresponding to significant events for relatives needed to be shared with the staff, the extension of the link with caregivers by evocating a new life after icu stay, the writing time as a countergift to the caregivers; ( ) the caregivers behaviour, including human skills detailed in many core values (kindness, availability, devotion, attention, goodwill, sensitivity) psychological support, emotional sharing, capabilities to give informations. relatives feel to be "at the center of all attention" in the same way as their loved ones. through the narration of icu experience, the caring relationship is characterized as follows: ( ) the caregiver becomes a close person with an equal relationship (feelings of friendship, emotional closeness); ( ) the icu team becomes a new family (contrasting with the poor living environment of icus); ( ) the relative becomes a caregiver (with appropriation of medical terms or speaking of his loved one as a patient); ( ) the caregiver is seen as a "super-hero" through an asymmetrical relationship with an overstatement of personal dedication and investment of the staff members (abnegation, vocation, involvement). the caring relationship impacts relatives' experience of intensive care in several ways: ( ) relatives are deeply touched by caregivers' human behavior, emotional support being a source of solace and resilience in particular for bereaved families; ( ) relatives express the idea that taking care of humans is not a valued and rewarded task and the emerging awareness of hospital realities and difficulties of work in the icu; ( ) the most striking transformational change in relatives is the perception of their own vulnerability and humanity, leading them to exhibit an outward-looking attitude (for example filling out their organ-donation card), and encouraging the icu caregivers to continue their missions for the others. conclusion thank-you letters provide both encouraging and informative messages for icu teams about relational care for patients and families notably the indivisibility of the families and their critically ill loved ones. the relatives' experience of the icu appears strongly influenced by the caring relationship in the way they express an authentic revelation of their own humanity and altruistic thoughts. the thematic content of thank-you letters questions determinants and fundamental values at stake in the patient-relatives-caregivers relationship. introduction far from medical paternalism, the doctor-patient relationship has now evolved to respect "the autonomy and patients' rights". changing behavior has been gradual, while the law offered the patient the freedom to consent to care and then of expressing their wishes regarding the therapeutic intensity they would benefit, in critical situations where consent would not be possible, through advance directives (ad) [ ] . their use is of paramount interest for intensivist in many critical situations. unfortunately, the use of ad remains marginal because of the unfamiliarity of patients with their use and an appropriation default by clinicians [ ] . the aim of our study was to investigate the perspective of the coming family physician generation on advances directives. patients and methods population of interest was general practitioner fellow (gpf) from class of to . we built an online questionnaire survey about knowledge and the place they want to give to ad in their forthcoming daily clinical activity. this questionnaire was sent to gpf emails obtained by universities, unions and via the official mailing lists of different regionals classes provided by the first contacted. descriptive analysis of quantitative data was expressed as mean and standard deviation, qualitative data in number and percentage. the comparison of continuous variables was performed by the student t-test and the comparison of categorical variables by a chi test. analyzes were conducted on biostatgv website and microsoft excel ® . results gpf answered the survey, mainly from ile de france (n = ), toulouse (n = ) and lille (n = ). for gpf the majority of patients do not know the ad ( . %) and % think that those who know do not know how to use it. . % of gpf think writing ad by patients requires better information. according to them, the information should concern the support offered in the icu ( . %), the use of mechanical ventilation ( . %), dialysis ( . %) and the evolution of patients after hospitalization in icu ( . %). nevertheless information on the prognosis of chronic diseases or organ failure seems interesting for only and . % of them respectively. . % of gpf wish to propose the drafting of ad to their patients. however, only . % of them are willing to suggest ad to patients with cancer or hematologic malignancies, . % to patients with neurological and/or degenerative disorders, . % to elderly patients. discussion despite the low proportion of the population we think these observations to be of interest because we probably selected the gpf the most interested in ad as the participation was not mandatory. conclusion a large majority of young of future general practitioner is willing to be involved in the implementation of ad with their patients, however the target population remains very limited, considering that half of them do not want to discuss ad with patients suffering from diseases potentially associated with icu admission or therapeutic intensity discussion. this study was conducted in adult intensive care units in public or private hospitals in four countries: canada, france, italy, spain. in each country, health care professionals were solicited for an exploratory interview about the sources of stress in the work environment: senior physicians, residents, experienced nurses (with more than years of experience in the service) and inexperienced nurses (with less than years of experience in the service). all the interview transcripts were analysed using an inductive coding approach. results one hundred and sixty professionals ( physicians and nurses) were included in the study. eight themes emerged from the analysis, and they concerned the stress linked to ( ) patient ( ) care, ( ) team, ( ) family, ( ) institutional context, ( ) environment, ( ) organizational context, ( ) individual dimensions. in each theme, sub-themes have been identified and determine more precisely the difficulties at work. discussion our findings emphasize the complexity of work in icus and show the specifics factors not taken into account in the generic stress scales such as stress in relation with family relationships, the end of life decisions and inequity of health care. conclusion the specific stress scale should allow to better identified stress in icu and to develop measures of prevention and support and training programs. introduction intensive care units (icu) is a place where caregivers face many constraints that can affect their physical and mental health due to the use of specific care and strong emotional charge related to patient death and pain of the families. the aim of the present study is to detect anxiety disorders and/or depression among staff working in icus. on september , a questionnaire was distributed to staff (medical and paramedical) operating in icus in the university hospital fattouma bourguiba monastir, tunisia ( medical icu, surgical icu, cardiologic ccus and nephrologic intermediate care unit). this questionnaire included demographic data of participants (age, sex, marital status, length of service, psychiatric history, consumption of anxiolytic and/or antidepressant) and the hospital anxiety and depression scale (had: scale composed by items to screen the anxiety (a) and/or depression (d) among hospital staff ). results during the study period, participants completed the questionnaire ( %), % of them were women, the median age was years ± . . forty-nine participants were doctors (the majority of them residents: / ). . % of participants (all paramedics) worked on night shift, seniority of more than a year in the icu was found in % of participants. . % of staff interviewed were married and only . % of them reported consumption of anxiolytics and/or antidepressants. . and . % of the participants had respectively symptoms suggesting anxiety and depression. the median had score was (iqr = ); the medical function seems to be significantly associated with the occurrence of symptoms of anxiety and depression compared to paramedics, however the type of icu (medical/surgical icus vs cordiologic/nephrologic icus) does not appear to be related to the occurrence of symptoms of anxiety or depression (table ) . conclusion anxiety and depression are common symptoms among caregivers in icus. improved conditions of work in these units should be a target to avoid burn out syndrome. none. anxiety, n (%) depression, n (%) introduction carbon monoxide (co) poisoning is one of the common causes of poisoning specially in the cold season, which leads to a significant morbidity and mortality. we retrospectively reviewed the medical data of patients who presented to the toxicology emergency department with co poisoning during january to march . we analyzed patients' characteristics, management, and outcomes. results a total of six hundred and sixty-six patients ( female and male), aged of ± years, were included; poisoning occurred between december and february in % of cases, secondary to an indoor heating system exposure in the majority of cases ( %). the estimated duration of exposure was . ± h [ . - h], with a mean carboxyhaemoglobin (cohb) level on arrival at . ± %. neurological changes were the most presenting symptoms including headache (n = , %), dizziness (n = , %), seizure (n = , . %) and loss of consciousness (n = , . %). digestive disorders involving vomiting and nausea were observed in . % (n = ). one woman without cardiovascular risk factors developed non stsegment elevation myocardial infarction complicated by lung edema. the majority of patients (n = , %) received normobaric oxygen during h (n = ) and h (n = ). hyperbaric oxygen therapy was administered at . ata during h to patients for neurological changes (n = ), pregnancy (n = ) and elevated cohb ≥ % (n = ). mechanical ventilation was required for patients, and admission into intensive care unit in patients ( %). death occurred in cases ( . %). conclusion the carbon monoxide poisoning is a common reason for emergency department visits in winter. the physician should be aware of the serious neurological and cardiovascular complications, if symptomatic treatment and oxygen therapy regimens were not respected. none. neuro-respiratory toxicity of baclofen in the rat: study of the concentrations/effects relationships and role of gabaergic introduction baclofen, a gaba-b receptor agonist is used as muscle relaxant agent and recently for the treatment of alcohol dependence. the number of poisonings has significantly increased since this new indication. clinical presentation of poisoning mainly includes sedation, hypotonia, respiratory depression and seizures. to characterize the neurorespiratory toxicity of this molecule at high doses, we aimed at investigating alterations in sprague-dawley rat ventilation and brain electrical activity after baclofen administration and studied their reversal by gaba-receptor antagonists. materials and methods rat ventilation was investigated using plethysmography and arterial blood gas analysis while brain electrical activity was studied using eeg with one implanted frontal electrode. three baclofen doses were used including . mg/kg ( % lethal dose- %), . mg/kg ( %) and mg/kg ( %). baclofen concentrations were obtained using hplc-msms assay. we modeled baclofen pharmacokinetics and analyzed the doses/effects and effects/concentrations relationships. results baclofen induced early-onset and prolonged dosedependent sedation (p = . ), hypothermia (p = . ), eeg and respiratory depression ( . ) characterized by significant increase in the inspiratory (p = . ) and expiratory times (p = . ). significant increase in paco and decrease in arterial ph and pao were observed at mg/kg (p = . ), peaking at min. eeg showed signal slowing, burst-suppression aspects and spikes peaking at - h post-injection without normalization at the end of the experiment at h. we did reverse baclofen-induced decrease in tidal volume with saclofen (a gaba-b receptor antagonist) and interestingly no alteration of baclofen-induced respiratory depression was observed with flumazenil (a gaba-a receptor antagonist). pharmacokinetic parameters of baclofen were obtained at the three doses and were dose-dependent. significant but non-linear relationships were observed between baclofen-induced effects and concentrations. conclusion baclofen causes dose-dependent neurorespiratory toxicity in rats. however, due to increased poisonings, its safety profile at high doses remains to be established in humans. none. poisoning was deliberate in % of cases. mean ingested dose was . ± mg. the majority of patients presented to the emergency room at . ± h after ingestion. digestive decontamination was performed in . % (n = ) of patients. clinical presentation was dominated by neurological symptoms; including coma (n = ), hypotonia (n = ), hyporeflexia (n = ), agitation (n = ), seizures (n = ) and delirium in case. hemodynamic manifestations included bradycardia in patients, three of them required atropine infusion. one patient presented with hypotension responding to vascular resuscitation. sixteen cases required mechanical ventilation. aspiration pneumonia was noted in cases. mean duration of ventilation was . h ± . mean hospital length of stay was h ± . complications included ventilation associated pneumonia in one case and moderate rhabdomyolysis in cases. all patients evolved favorably. there is no correlation between coma and assumed ingested dose. conclusion baclofen overdose causes mainly neurological effects and except for bradycardia cardiovascular effects were uncommon. prognosis is good if full supportive care is administered properly. none. introduction the lack of an effective treatment for the maintenance of abstinence from alcohol has led physicians to take an interest in baclofen. beyond efficacy, safety of baclofen, prescribed in high doses, is a concern, especially in case of drug overdose. indeed, patients with chronic alcohol abuse frequently develop psychiatric disorders, and are at risk of voluntary drug intoxications. thus, we set up a retrospective study to describe morbidity and mortality associated with baclofen overdose. conclusion baclofen, prescribed in high doses, may lead to severe intoxications: self-poisonings frequently require endotracheal intubation and are associated with an increased risk of death. dialysis decreases baclofen elimination half-time but clinical relevance of this difference could not be determined. none. introduction baclofen, a gaba-b receptor-agonist with muscle relaxant properties established since , has been recently used at elevated doses to treat dependence to ethanol. the number of prescriptions has exponentially increased without an exact evaluation of its toxicity. we aimed to describe acute baclofen poisoning requiring intensive care unit (icu) admission and study the relationships between the toxic encephalopathy and the plasma baclofen concentration. we conducted a single-centre retrospective study including all baclofen-poisoned patients admitted to the icu in - . when requested by the clinical situation, repeated electroencephalograms and measurements of the plasma baclofen concentrations were performed. toxic eeg encephalopathy on a scale of zero to five was graded according to the international rating system (markand, ). plasma baclofen concentration was determined using liquid chromatography coupled to mass spectrometry in tandem developed with a quantum ultra apparatus (thermo fisher scientific) and electrospray source ionization in positive mode (limit of quantification: ng/ml). linear regression and chi- or mann-whitney tests were used as requested for subgroup comparisons. baclofen pharmacokinetics and the relationships between the toxic encephalopathy and the plasma baclofen concentration were modeled using winnonlin software v. ) were closed to the observed values reported at therapeutic doses. the relationship between baclofeninduced encephalopathy as a function of the baclofen concentrations was described using a sigmoidal emax model. conclusion baclofen poisoning may be life-threatening. toxic encephalopathy is well-described with eeg and its grade correlated to the baclofen concentration. prescribers should be aware of the dangers of baclofen which benefits to treat dependence to alcohol are still lacking. none. results initial examination suggested that an illness other than bacterial meningitis was the cause of patients' complaints. first hypothesis was meningitis receiving uncomplete dosage regimen of antibiotics. thereafter owing to apparent loss of consciousness with abnormal eyes movements, non-tonico-clonic seizures were considered meanwhile. the ratio of individuals less y-o to those equal to and greater was / %. the male to female ratio was / %. the mean duration of hospitalisation was . ± . days (extremes - days). extrapyramidal syndrome predominant on the upper part of the body was noted by paediatrician neurologists who suggested considering a genetic disease. however, signs and symptoms were present in people from different families in different areas at the same time. the definitive diagnosis made on pictures and videos of children and adults and was facio-troncular dystonia resulting from drug-induced adverse effect. four urine samples were collected in children and sent to a toxicological laboratory in france. all urine samples were positive for haloperidol meanwhile the other causes of facio-troncular dystonia were excluded, including other neuroleptics, metoclopramide, antidepressants, amodiaquine, anti-histaminic drugs, anti-epileptics, and cocaine. from january to august , hospitalisations were recorded in patients. looking for the source of haloperidol showed that tablets sold as 'diazepam' and consumed by symptomatic patients contained haloperidol as the sole active pharmaceutical ingredient, suggesting that this large outbreak was due to haloperidol toxicity from falsified diazepam. initial treatment was diazepam to relieve severe facio-troncular dystonia which was efficient but resulted in long-lasting sedation more especially in children. a dosage regimen using bipéridène administered by intravenous and oral route was refined to prevent adverse effects related to this anticholinergic agent used in children. the complete reversal of the facio-troncular dystonia was the antidotal evidence supporting the toxicological diagnostic. the mortality rate was less than % meanwhile the direct causal relationship with adr is questionable. an epidemiological study, including toxicological analysis in controls in ongoing. indeed, facio-troncular dystonia induced by haloperidol does not result from a drug overdose but is an adr occurring in about % of patients treated with haloperidol. who is involved in the inquiry related to this counterfeature involving different countries. the cause of the error is presently under investigation. discussion this outbreak emphasizes the need to consider toxicity resulting from counterfeatured medicines when facing collective atypical signs and symptoms in countries with unrestricted access to medication with limited control of qualities of the medicinal drugs. conclusion counterfeatured medicinal drug may result not only in poor efficacy but also in onset of unexpected outbreak of unknown diseases that should suggest a toxic origin. in late -early , médecins sans frontières (msf) had to face an outbreak of severe facio-troncular dystonic syndrome (ftds) in north-east congo. this outbreak resulted from counterfeature of pills sold as diazepam. toxicological analysis revealed one pill contained about mg of haloperidol. ftds induced by haloperidol does not result from a drug overdose but is an adverse drug reaction (adr) occurring in about % of patients treated with haloperidol. nine-hundred and twenty-five individuals were admitted in msf structures for ftds. the ratio of individuals less than y-o and equal to or greater of age was / %, including ( . %) of children less than y-o. initial treatment was based on diazepam which relieved ftds but resulted in long-lasting sedation, preventing given any drug by the oral route. owing to the definitive diagnosis, a shift to the use of a more specific antidote was chosen. biperiden was selected as existing in the intravenous and oral form in the swiss pharmacopea. the study was approved by the ethical committee of the ministery of health of the republic democratic du congo. patients and methods as a whole, biperiden was used in cases ( % of the total). treated children presented with severe dystonia as evidenced by inability to cooperate and to swallow. verbal informed consent was obtained from relatives. the dosage regimen to treat drug-induced dystonic syndrome in the swiss pharmacopea is as follows: for parenteral use in children, intravenously or intramuscularly: . mg/kg or . mg/m bsa every , according to response and tolerance; a maximum of four doses per day should be used. the internal msf recommendations for biperiden use in children were . - . mg/kg of body weight that might be repeated four times a day. initially, biperiden administration was administered under medical supervision by the msf referent at the scene. results there was no pediatric preparation of biperiden. accordingly, the adult preparation was used in children. the preparation contained mg of biperiden in one milliter of solvent. the initial planned dose for children of y-o and less and those up to y-o were and mg, respectively. the mg ( ml) of biperiden was diluted in ml of saline resulting in a final dilution of mg/ml. six children were treated according this dosage regimen. however, the one mg dose was either of limited efficacy while being associated in others of signs suggestive of adr, including agitation, heart rate greater than b/ min, the upper limit for children aged of y-o and less. two children greater than y-o presented severe abnormal behavior resulting in an attempt at escape. owing to question about safety, the dosage regimen was changed, as follows: mg ( ml) of biperiden was diluted with ml of saline resulting in a final dilution of . mg/ml. an initial dose of . mg was administered intravenously as a bolus dose. the effects were looked for over min. in the absence of improvement in facial dystonia, a second bolus dose of . mg was administered, a third dose could be considered min later if the ftds did not resume. the cumulative initial dose should not be greater than mg. in addition to the reversal of facial dystonia, the therapeutic effect of biperiden included the return of swallowing to normal allowing to give further doses of biperiden by the oral route for three days. the first oral dose was administered no less than h after the last initial dose at a dose equal to the efficient initial cumulative dose. the following doses were halved every h. no adr related to biperiden were reported using this dosage regimen. the mean duration of hospitalisation was . ± . days. discussion the bioavailability of biperiden by the oral route is equal to %. accordingly, the corresponding intravenous dose should be divided by a factor three. dosage regimen of anticholinergic drugs in children are poorly documented. the dosage regimen recommended by the pharmacopea resulted in frequent and severe adr. titration of biperiden resulted in efficient and safe dosage. conclusion when biperiden administration is required by intravenous route in children of y-o and less, biperiden should be administered intravenously and titred using bolus dose of . mg till the therapeutic effect is obtained. introduction severe poisoning by rodenticides is frequent. it represents nearly % of patients admitted to the new intensive care unit (icu) of the region. that is why we decided to perform this study. the aim of this work was to describe the epidemiology, clinical features and management of all patients admitted to our unit for acute poisoning with rodenticides. patients and methods it was a retrospective study performed in the year from january to december. the study included all patients admitted in the icu for rodenticide poisoning. results patients were enrolled in the study. our patients were young with a mean age of ± years. poisoning was more common in females (n = ; %). the mean delay between rodenticide poisoning and first medical contact was about ± h in the cases where this information. most of our patients ( %) attended the emergency department of zaghouan with a non-medical transportation. it was a suicide attempt in most cases ( %) and an accidental poisoning in % of patients. the most frequent cause of poisoning in our study was organophosphorus pesticide (n = ; %). the second cause was alpha-chloralose poisoning with seven cases ( %). one patient ingested accidentally an anticoagulant rodenticide. most of patients had ingested (oral route) the rat poison (n = ; %). clinical examination found normal vital signs in ten cases ( %). nine patients ( %) had a shock, eight patients ( %) had an acute metabolic disorder and five patients ( %) had acute respiratory failure or were comatose. all patients enrolled in the study were admitted in the icu for a period of clinical observation of h. stomach pumping (gastric lavage) was performed in patients ( %). an antidote which was atropine was needed in twelve patients. three patients ( %) who ingested alpha-chloralose needed intubation and mechanical ventilation. all patients had a good outcome and were discharged from icu and from hospital. the mean icu length of stay was ± days. conclusion this is the first study of acute poisoning with rodenticides admitted in the new icu. the results of our study were similar to those published in recent literature. cases of acute poisoning with rodenticides reported in this work were not severe. none. introduction the systemic arterial load imposed to the left ventricle (lv) is a major determinant of normal/abnormal cardiovascular function. the lv mean ejection pressure (lvmep) is the best estimate of load faced by the lv throughout ejection. the contribution of the steady and pulsatile blood pressure (bp) component of arterial load to lvmep is debated. we studied the hemodynamic correlates of lvmep using carotid tonometry. intensive care unit patients equipped with an indwelling catheter were studied, thus allowing precise calibration of the tonometer. patients and methods carotid tonometry (complior analyse ® alam medical, france) was prospectively performed on hemodynamically stable, spontaneously breathing patients ( f, mean age ± sd = ± years). carotid waveforms were calibrated from diastolic bp and time-averaged mean bp invasively obtained at the radial (n = ) and femoral (n = ) artery. all patients were free of aortic stenosis. lvmep was the area under the systolic part of the carotid pressure waveform divided by ejection time. results lvmep ( ± mmhg) was strongly related to central systolic bp ( ± mmhg; r = . ) and was also related to mean bp (r = . ), peripheral systolic bp (r = . ), peripheral (r = . ) and central (r = . ) pulse pressure (each p < . ). the lvemp was not related to age, heart rate and stroke volume. systolic pulse wave amplification ratio from carotid to periphery was . ± . . conclusion lvmep was most strongly related to central systolic bp, which combines the influences of the steady and pulsatile components of central arterial load (r = . ). lvmep was less strongly related to peripheral systolic bp, which may be less informative given variable systolic pulse wave amplification across patients. introduction myocardial dysfunction is one of the main predictors of poor outcome in septic patients, with mortality rates next to %. many pathological findings were found in the sepsis induced cardiomyopathy including myocardial ischemia, alterations in microcirculation and proinflammatory cytokines. the aim of this study was to assess the prognostic value of a recently developed highly sensitive cardiac troponin i (hstni) assay in patients with septic shock. we performed a prospective observational study in septic shock icu patients within h of admission. exclusion criteria were age > years; pregnancy; post-cardiac arrest and braindead. hstni was measured soon after admission and , , and h after. patients were subjected to transthoracic echocardiography (tte) at study inclusion and regular biochemical and hemodynamic assessments were performed. pearson's chi square and fisher's exact tests were used. p < . was considered significant. conclusion circulating hs-ctni is present in patients with septic shock. a rise of hstni may be an indicator of poor outcome. also, right heart functional abnormalities exist in patients with septic shock. none. evolution of the right distribution width as a pronostic marker during the differents state of shock introduction right distribution width (rdw) has been recently proposed as a pronostic factor in different pathologic situations and especially to the septic patients who stay in icu. some works substantiate the relationship between an alteration of the red blood cell rheology during the septic shock and a severe state of the disease. no one has studied the rdw between the differents shocks yet. we are going to determinate the relationship between rdw and apache ii score, mortality rate in the intensive care unit (icu), at the hospital, at the day and . we investigated those parameters near patients who were admitted at the icu and needed norepinephrine between the first of march and the st of december. they were stratified in différent groups: septic shock n = , cardiogenic shock n = , hemorragic shock n = and obstructive shock n = . results we did not observe any correlation between the rdw and the icu mortality, hospital mortality and at the day and . only a poor significant correlation has been found between the cardiogenic shock and the mortality rate: at the hospital (p = . ), at day (p = . ) and at the day (p = . ) but not in the icu (p = . ). the receiver operating characteristics (roc) curves do not show significant differences between rdw, apache ii score and icu mortality rate or intra hospital. the sample of the hemorrhagic shock and obstructive shock was not usable for this calculation. compared to other studies which were focused on the septic shock where the mortality was approximately %, we determinated a mortality rate near %. conclusion the delta of the rdw d /d did not present any correlation with the mortality rate. in our study, the rdw in the different kind of shocks do not look like to be a good predictive marker of the mortality, except for the patients included in the cardiogenic shock where a poor significant correlation could be highlighted. conclusion cardiogenic shock was the most frequent complication of ami who led to icu admission, whereas mechanical complications are rare at the era of early coronary reperfusion strategies. in addition to severity score, serum creatinine and cardiogenic shock appeared as independent factors of hospital death. none. introduction pulmonary embolism (pe) in high-risk is a partial or total obliteration of the pulmonary arterial network by a fibrin-clot cruoric more than %, the management requires a rapid reduction of pulmonary arterial resistance and right ventricular post load through rapid revascularization by thrombolysis. our aim is to determine the value of thrombolysis in pulmonary embolism and describe the clinical, paraclinical and outcome pulmonary embolism at high risk. patients and methods this is a descriptive study of cases of pulmonary embolism at high risk admitted to the cardiology department to chu oran between and . signs of gravity of (pe) comprising: syncope, circulatory collapse, cardiogenic shock or acute pulmonary sonographic sign of heart. it was confirmed in chest ct. all patients received thrombolysis using the protocol accelerated by two types of molecules: streptokinase or actilyse. the sex ratio was . ; mean age years, ranging from to years; risk factors were dominated by contraception was % and the postoperative % the clinical picture was dominated by cardiogenic shock in % of cases. % cardiovascular collapse and syncope in %; doppler echo all patients had signs of dysfunction of the right ventricle represented by the dilatation of the right cavities and pulmonary hypertension. the cta found a (pe) bilateral in % right in %. thrombolysis using actilyse in patients and streptokinase in cases. the outcome was favorable in patients; with two cases that are complicated by chronic pulmonary heart and the death of patients with cancer. discussion the female predominance is explained by the increase of risk factors hormonal contraception, whose first generation combination hormonal. our patient had a high probability with clinical signs of severity based on the score wells [ ] . this diagnosis was confirmed by chest ct; which shows the vascular bed obstruction degree with a very good sensitivity and specificity. the suspect patients with severe pe and that presented signs of acute pulmonary heart ultrasound have effectively (pe). the indication of thrombolysis was chosen on hemodynamic criteria; success is found in % of patients with improved hemodynamics dice the early hours. this success is explained by the role of thrombolytic in lysis clot to obtain pulmonary arterial revascularization; and reduce pulmonary arterial resistance and the right ventricular afterload which accelerates the healing of right heart failure and improvement of pulmonary capillary volume. the cases who developed a chronic pulmonary heart; it was done immediately a right ventricular dysfunction with pulmonary arterial outset of very high pressures suggestive that the embolism occurred on an already pathological right heart. no cases of massive bleeding were noted in our series. conclusion severe pulmonary embolism is burdened with high mortality; diagnosis is based on the stratification of risk score, was facilitated by the non-invasive strategies that articlent around the doppler echocardiography and ct angiography; thrombolysis can reduce the high mortality related to severe pulmonary embolism. introduction hypertension is a frequent motif for admission to emergencies. the diabetic is increasingly exposed to this risk [ ] . the objective of this study is to evaluate the proportion of diabetic patients presenting to the emergency department with high blood pressure (bp) and to identify their epidemiological and clinical characteristics. introduction sepsis associated liver dysfunction (sld) is usually attributed to systemic and/or microcirculatory disturbance. hypoxic hepatitis, also known as shock liver or ischemic hepatitis, is a life threatening event associated with high morbidity and mortality. doppler ultrasonography is a non invasive method to measure doppler hepatic hemodynamic parameters. the primary objective of this study was to assess the accuracy of the hepatic hemodynamic parameters (portal venous blood flow pvbf and resistance index of the hepatic artery hari) in predicting sld in septic shock patients. the secondary aims were to identify factors associated with sld, investigate the effects of volume expansion (ve) on systemic and intrahepatic hemodynamics and to assess the intra-and interoperator reproducibility. we also analyzed -day mortality. in a prospective design, we included consecutive patients with septic shock ( males; median age: . years) admitted to the icu with septic shock in charles nicolle hospital of tunis from february to july . all patients were resuscitated following the surviving sepsis campaign guidelines. we measured systemic hemodynamic variables (mean arterial pressure (map), and cardiac index (ci)) and performed hepatic doppler before and after volume expansion. we measured pvbf and computed the hari. we recorded the liver function tests (alt, ast and bilirubin) for h. sld was defined as an increase in serum bilirubin ≥ µmol/l (hepatic sofa ≥ ). accuracy of the hepatic hemodynamic parameters to predict sld was measured by the area under the roc curve. p < . was taken to indicate statistical significance. the median sofa score at t was points and the median igs score was points. the sources of infection were as follows: the lungs (n = ), the abdomen (n = ) and the urinary tract (n = ). the incidence of sld in our cohort was . % (n = ). there was no significant difference between "sld group" and "no-sld group" in all hepatic hemodynamic parameters especially the pvbf and the hari. lactate levels were significantly higher in patients with sld (median . vs. . mmol/l). similarly, the platelet count was significantly lower in the "sld group" [mean (± sd) . ± . ( /l) vs. . ± . ( /l); p = . ]. there was no difference in duration of mechanical ventilation, icu length of stay and -day mortality between the groups. the pvbf was significantly lower in patients who died before d (median: vs. l/min in the survivors; p = . ). volume expansion caused a significant increase in ci, mean hepatic artery velocity and the pvbf. the intra-and interoperator reproducibility was good to excellent for the systolic and mean velocities of the hepatic artery, portal vein diameter and the pvbf. conclusion our results don't support the hypothesis that the hepatic sonography is predictive of sld in septic shock. our pilot study showed higher lactate levels and hematologic sofa in sld group. the pvbf was significantly lower in patients who died before d . more experience will be necessary to define the ultimate role of doppler ultrasonography in the evaluation of hepatic perfusion in patients with septic shock. introduction early surgery is the current trend for management of patients with valvular disease. that said many of them, particularly from developing countries, are still operated at a very advanced stage of disease. despite improvements in myocardial protection and surgical techniques, postoperative care after multiple valve surgery (mvs) for advanced rheumatic heart disease (rhd) remains to be a clinical challenge. we conducted a study to determine postoperative complications and morbidity-mortality risk factors in this subgroup of patients. results sixty-two patients were included: with out-of-hospital refractory cardiac arrest and with in-hospital refractory arrest. the initial rhythms was shockable rhythm in ( %) cases. at ecls initiation, the mean no flow was . ± . min and mean low flow (time between the time of refractory cardiac arrest and time at which an ecls flow was provided) was ± min. the mean ecls flow rate was . ± . l/min. initial blood test results were: arterial ph = . ± . and plasma lactate = . ± . mmol/l. eleven ( %) patients survived ( / ( %) acute coronary syndrome, / ( %) severe poisoning due to drug intoxication, / ( %) dilated cardiomyopathy, and / ( %) others). survival was lower for patients with out-of-hospital refractory cardiac arrest, of ( %), than for patients with in-hospital refractory cardiac arrest, of ( %), respectively, p = . . as expected, out-of-hospital refractory cardiac arrest was associated with a more prolonged low flow ( ± min vs ± min, p < . ) and a more profound acidosis (ph . ± . vs . ± . , p = . and arterial lactate . ± . vs ± , p = . ). in univariate analysis, survival was lower for patient with refractory cardiac arrest unrelated to drug intoxication, vs %, respectively, p = . . in addition, mortality was associated with arterial ph ( . ± . vs . ± . , p = . ) and low flow ( ± vs ± min, p = . conclusion in a highly selected group of critically ill patients with refractory cardiac arrest, the potential beneficial effect of ecls could be due only to its clinical impact on reversible causes of circulatory failure (i.e. severe drug intoxication in our cohort). further studies are needed to clarify whether the use of ecls could be considered as a disproportionate tool, specifically in patients with out-of-hospital refractory cardiac arrest due to acute coronary syndrome or associated with prolonged low flow or a profound acidosis. none. post-cardiac arrest shock treated with veno-arterial extracorporeal membrane oxygenation: an observational study and propensity-score analysis wulfran bougouin , nadia aissaoui , alain combes average time between introduction and removed of the ecd was h ( - ). among the esogastroduodenoscopy performed, ( %) were strictly normal. endoscopy showed minor gastric injuries in patients ( %). within these patients, ( %) also presented minor esophageal injuries. esogastric injuries characteristics were mostly similar to usual orogastric probe injuries. one patient ( %) experienced a serious ulcerous esophagitis mimicking a peptic esophagitis, not firmly related to the ecd. no patients necessitated hemostatic local procedure and no significant gastrointestinal bleeding was observed. eight patients ( %) were alive at d , including patients ( %) with a cerebral performance category score of . this compares favorably to outcomes from previous studies. conclusion ecd seems an interesting and safe semi-invasive method of cooling in ohca patients treated with °c-ttm. although it seems slower than more invasive devices to reach °c, ecd was able to strictly maintained the tt within the maintenance phase of ttm. further studies will be necessary to define the exact place of this new device within the cooling strategy in patients necessitating a precise ttm-strategy. none. fig. see text for description introduction since post-cardiac arrest care might influence the outcome, characteristics of receiving hospitals should be integrated in survival evaluation of patients transported in hospital. we aimed at assessing the influence of care level center on survival at discharge in a regional registry of out-of-hospital cardiac arrest (ohca). we prospectively collected utstein and in-hospital data for all non-traumatic ohca patients, in whom a successful return of spontaneous circulation (rosc) had been obtained, from a large metropolitan area (great paris). receiving hospitals were categorized in groups (a, b, c) depending on their respective characteristics (annual volumes, / catheterization availability and temperature management use). we compared patients' characteristics in the groups and performed a multivariable logistic regression using discharge survival at endpoint. results during the study period (may -dec ), patients were admitted in hospitals ( in group a, in group b and in group c). overall survival rate at discharge was / ( %). patients' baseline characteristics significantly differed, as hospitals from group a treated younger patients and more frequent shockable rhythms (p < . ). unadjusted survival rate differed significantly among the groups of hospitals (respectively , and . % for a, b, c, p < . ). however in multivariable analysis, the category of hospital was no longer associated with survival. conclusion in this population-based study, characteristics of receiving hospitals are not associated with survival rate at discharge. this could result from the strategy used for triage, which aims in matching patients' characteristics and resources. introduction acute kidney injury (aki) commonly occurs after cardiac arrest and is associated with an increased mortality and a delayed awaking. early recognition of aki remains challenging, given that serum creatinine increases belatedly after aggression. introduction out-of-hospital cardiac arrests (ohca) are an absolute urgency and have a very poor prognosis. pediatric guidelines differ from adult guidelines for cardiac arrest management. since , adult guidelines apply from the onset of puberty. the main objective was to describe the epidemiological characteristics and outcome of ohca victims while taking puberty into account. the secondary objective was to determine the prognostic factors for survival at d . materials and methods all patients less than years of age, victims of ohca between july , and september , care by a mobile emergency and resuscitation service (smur) participating in french national cardiac arrest registry (réac) were included. patients were split into groups: prepubescent patients (named "children": girls - years, boys - years), pubescent patients (named "adolescents": girls from to years and boys from to years) and "adults" (men and women - years). the "adolescents" group was consecutively compared to the "children" group and to the "adults" group. results children, adolescents and , adults under the age of have been included. ohca in adolescents occurred more often on public roads ( %) or in public places ( %) and were more often traumatic ( %) than those in children and adults. respiratory causes were more frequent in children ( %) than in adolescents ( %) and adults patients ( %). the proportion of shockable rhythm increased with age ( , and % for children, adolescents and adults respectively). survival at d was greater in adolescents ( %) than in children ( %) and adults ( %) (p = . and p = . respectively). in the studied groups, initial shockable rhythm was a survival factor at d (respectively or [ . - . ] for children, adolescents and adults). other risk factors are described in table . conclusion adolescents had better survival at d than the others groups. adolescents and adults had shockable rhythm more often than children. moreover, respiratory failure was less frequent in adolescent and adults patients compared to children. puberty seems to be a good limit to differentiate pediatric patients with ohca. none. introduction non-invasive ventilation (niv) is an effective alternative to endotracheal mechanical ventilation (mv) in the management of acute respiratory failure (arf) patients. nevertheless, it can be still difficult to assess its real feasibility, application and outcome in daily clinical practice. therefore, we report our clinical experience with routine use of niv since the last national recommendations ( ). our aims were to evaluate the clinical efficacy and outcome of niv, and to identify predictive factors for niv failure based on a daily use. patients and methods we conducted an observational retrospective single-center cohort study by reviewing all medical records from january to december in our -bed medical intensive care unit (icu). eligible patients were those having received niv during their icu stay. two groups were defined according to the indication of niv: niv for hypoxemic or hypercapnic arf (arf-niv), and niv used in the post-extubation period for weaning, prevention or treatment of post-extubation arf (post-extubation niv).the main evaluation criteria were the incidence of niv use, success/failure rate of niv and risk factors for niv failure in each group. niv failure was defined as the need for stopping niv whatever the reason (intubation, intolerance, death) within days after its initiation. ( ; ), and was longer in the post-extubation niv group ( days ( ; ) ) than in the arf-niv ( days ( ; ) for hypoxemic arf, ( ; ) for hypercapnic) (p < . ). the overall icu mortality was . % ( . % in hypoxemic group, . % in hypercapnic group, and . % in post-extubation niv group) (p = . ). in multivariate analysis, the main risk factors for arf-niv failure were: saps ii on admission (p < . ), absence of cardiologic history (p = . ) and the cause of arf (p = . ) with a higher failure rate for pulmonary infections than acute cardiogenic pulmonary edema (or . , p = . ). for post-extubation niv, the only independent risk factor for failure was normocapnia before niv initiation (p = . ). conclusion our large longitudinal study demonstrates the feasibility and efficacy of niv applied in daily clinical practice. provided it is performed in a suitable environment by an experienced team, niv should be considered as a first-line ventilatory treatment in various etiologies of arf and a very useful ventilatory support in the postextubation period. nevertheless, risk factors for niv failure should be known by icu clinicians, hypoxemic arf remaining the more difficult indication to manage with niv. réanimation médicale, hôpital saint-louis, paris, france; service de biostatistique et information médicale, hôpital saint-louis, paris, france; réanimation, institut paoli-calmettes, marseille, france; réanimation introduction acute respiratory failure (arf) is the leading cause for icu admission in immunocompromised patients. in these patients, oxygenation strategy is of major interest to avoid the need for mechanical ventilation (mv), which is associated with high mortality rates. in that setting, use of non-invasive ventilation (niv) and oxygen therapy with high flow nasal cannula (hfnc) could be interesting alone or in association, but data about initial ventilation strategy in immunocompromised patients are controversial. to assess how initial oxygenation strategy actually influences the risk of mv on the coming day within the three first days of icu stay. the study end-point was the need for mv on the coming day. we restricted analyses to these first three icu days given, based on our own experience, most of mv was expected to occur by then. we performed a post hoc analysis combining three prospective studies of critically ill immunocompromised patients (two randomized control trials, the ivnictus and the minimax studies and one prospective cohort, the trial-oh study). we only considered patients with arf and a delay between icu admission and study inclusion less than h. we excluded patients who required invasive mv within the first day, those with an icu stay less than day and those with acute pulmonary edema diagnosis at icu admission. in order to estimate and compare the causal effect of daily respiratory management strategy on the probability of intubation in the coming day, we computed inverse probability of treatment weights (iptw) using propensity-score, defined as the probability of actual treatment selection conditionally on observed covariates. to handle confounding in such dynamic regimens, we considered marginal structural models (msm), which have been proposed to estimate the causal effect of a time-dependent exposure when time-dependent covariates that can be affected by the previous treatment are present. two treatment exposure models were considered: niv versus oxygen therapy regardless the device (model ) and hfnc alone, niv alone versus niv + hfnc versus standard oxygen therapy alone (model ). results patients were included in the study. in model , there was no difference between niv and oxygen groups on mv whatever the landmark time. in model , while the unweighted or for intubation at day was significantly higher in the niv group (or . , %ci . - . ) and hfnc group (or . , %ci . - . ) than those in the standard oxygen alone group, these differences disappeared in the weighted samples. using msm, no effect of the oxygenation strategy on mv was found, regardless of the oxygenation devices but the landmark time was associated with a reduced occurrence of mv. conclusion we found no evidence of any significant difference from several oxygenation strategies on mechanical ventilation probability during the first days of icu in a large cohort of immunocompromised patients with arf. none. introduction the role of noninvasive ventilation (niv) is debated in the management of patients with acute hypoxemic respiratory failure. a recent study showed that patients treated with high-flow nasal cannulae oxygen therapy (hfnc) had lower intubation and mortality rates than those treated by the association of hfnc with niv ( ). high tidal volumes (vt) delivewred with niv may be associated with an increased risk of intubation ( ) . we aimed to identify risk factors associated to intubation, in hypoxemic patients with acute respiratory failure and especially the role of vt under niv. patients and methods this is an ancillary study from a multicenter, randomized, controlled trial including patients with acute hypoxemic respiratory failure (florali-study). we focused on only patients with moderate or severe hypoxemia (pao :fio ratio ≤ mmhg) and we excluded those with mild hypoxemia. the criteria for intubation were predetermined including worsened or persisted respiratory failure, impairment of neurologic status and hemodynamic instability. results after adjustment on the oxygenation strategy, the two factors independently associated with intubation were the presence of bilateral pulmonary infiltrates at admission (or . simulation conditions enables to reproduce its occurence, using different types of tools, from physiological parameters to heart rate variability and psychocognitive tests. future research is required to evaluate the impact of these parameters on teaching. none. with stratification by centre and operator experience. an only inclusion criterion was: "patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if: contraindication to orotracheal intubation (e.g., unstable spinal lesion); insufficient time to include and randomize the patient (e.g., because of cardiac arrest); age < years; pregnant or breastfeeding woman; correctional facility inmate; patient under guardianship; patient without health insurance; refusal of the patient or next of kin to participate in the study; previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess occurrence of spo < % during intubation procedure between groups of preoxygenation: bvm (at a minimum flow of l/min, niv ( % fio ), hfnc (at a minimum flow of l/min, with % fio ), and nrm (at a minimum flow of l/min). between-groups difference in desaturation occurrence was adjusted for baseline covariates significantly associated with the group membership (p < . ). multivariate analysis of the occurrence of a desaturation (< %) was performed using logistic regression. bag-valve mask was considered reference. results baseline characteristics were showed in table . groups were similar at baseline except for pao /fio ratio. in univariate analysis, age (p = . ), saps (p = . ), pao /fio ratio (p = . ),spo (p = . ) and method of preoxygenation (p = . ) were associated with occurrence of desaturation below %. in multivariate analysis, spo at randomization and method of preoxygenation were only predictors of desaturation below %. bvm and hrm were associated with similar risk of desaturation occurrence whereas niv (or . introduction intubation procedure is a challenging issue in intensive care unit (icu) [ ] . cardiac arrest related to intubation in critically ill adult patients has been poorly studied. the studies were not powered to conclude on this rare outcome [ ] . the main objective of our study was to establish the incidence of cardiac arrest and to assess the risk factors of cardiac arrest in a large prospective database of intubation procedures performed in icu. five prospective studies were included, with similar data collected before, during and after intubation procedures using the same methodology. the primary outcome was the incidence of cardiac arrest related to intubation. the secondary outcomes were the death (cardiac arrest without return of spontaneous circulation (rosc)), the cardiac arrests with rosc, the complications related to intubation, the length of icu stay and the -day mortality. the factors associated with cardiac arrest related to intubation procedures were assessed by univariate and multivariate analysis based on patient, provider and practice characteristics. results among the intubation procedures included, cardiac arrests ( . %) occurred, including with rosc ( . %) and without rosc ( . %). main patient, provider, procedure characteristics and outcomes according to cardiac arrest related to intubation are presented in table . in multivariate analysis, the independent predictors of cardiac arrest related to intubation were low systolic blood pressure prior to intubation, hypoxemia prior to intubation, no preoxygenation, overweight or obesity and age > years. mortality rate at day was significantly lower in patients intubated without cardiac arrest ( . %, of ) than with cardiac arrests overall ( . %, patients of , p < . ) and cardiac arrest with rosc ( %, patients of , p < . ). conclusion cardiac arrest related to intubation in adult icu is not a rare event occurring in . % of cases with high immediate mortality of . % and at day of . %. we identified five independent risk factors to cardiac arrest which of them could be modifiable. optimal preparation to intubation procedure could help to prevent those cardiac arrests. introduction naasotracheal intubation (nti) has been progressively given up in favour of the orotracheal intubation (oti) in intensive care unit (icu). this could be explained by more frequent infectious (sinusitis and ventilator associated pneumonia) and non-infectious (epistaxis, turbinates bones injury) complications the former being thought to be more frequent with nti. however, whereas infectious sinusitis is a risk factor for vap, no study has yet demonstrated that oti decreases the infectious sinusitis rate compared with nti. furthermore, nasal route could improve patient comfort and decrease auto-extubation. finally nti can be performed without laryngoscopy with less risk of lips and dental injury. in this prospective study, we aimed to compare the complication of nti and oti and to assess the comfort of the patient. we performed a prospective observational study in a -bed medical icu including patients requiring endotracheal intubation. the intubation route was let at the discretion of the physician in care of the patient, however oti was compulsory in case of cardiac arrest, severe hypoxemia (p/f < when available) and clotting perturbation. for each patient, age, sex, sapsii, mechanical ventilation duration. intubation route were recorded as well as complications during the placement of endotracheal tube. infectious and non infectious complications during invasive ventilation period were also recorded. in patients who were successfully extubated, pain, burning feeling, dryness and the wish of tube removal were assessed using visual analogic scales (vas conclusion despite its small size, and the absence of randomization, the present study suggests that nasotracheal intubation improves the comfort and the tolerance of tracheal intubation and is not associated to higher rates of vap. none. effect of mode of hydrocortisone administration in patients with septic shock: a prospective randomized trial oussama jaoued , rim gharbi , najla the baseline characteristics of patients were similar between the two groups. sepsis was secondary to community-acquired infection in % of cases. there was no difference in mortality between groups ( % in continuous groups and % in discontinuous group). sofa score was significantly higher at days , and in discontinuous group. length of stay, duration of mechanical ventilation, number of day without vasopressors, and the occurrence of adverse events were similar in the two groups. conclusion the mode of hydrocortisone administration in patients with septic shock has no influence on morbidity or mortality. the occurrence of adverse events was similar. introduction widespread activation of coagulation with platelet consumption is a pathophysiological feature of severe sepsis and septic shock. thrombocytopenia, either defined by platelet count below g/l or by a significant relative - -percent decrease in platelet count is a potent poor prognostic factor in sepsis. besides their role in hemostasis, platelets also carry various immune and inflammatory functions that are likely to impact on host defense against infections. we aimed to assess whether changes in the platelet count induced by sepsis is associated with the development of subsequent nosocomial infections. patients and methods patients were obtained from two prospective studies about immuno monitoring of dendritic cells and innate-like lymphocytes in critically ill septic patients ( , ) . adult patients with severe sepsis and septic shock were included. exclusion criteria were any immunosuppressive condition (hematological malignancy, hiv infection at any stage, bone marrow or solid organ transplantation, daily corticosteroid therapy > . mg/kg prednisone-equivalent, chemotherapy or any other immunosuppressive treatments), pregnancy, do-not-resuscitate orders on admission. in addition patients who died or who received platelet transfusion during the first week after icu admission were also excluded. platelet counts were collected on the day of sepsis diagnosis (d ) and then on d , d and d . the relative variation in platelet count at day n compared to day was calculated as follows: (count at day n − count at day ) × / (count at day between between d and d , between d and d and between d and d were also similar between patients with and without icuacquired infections (fig. ). discussion in this preliminary study from selected cohorts of nonimmunocompromised patients, sepsis resulted in mild alterations in platelet counts, making it unlikely to become associated with the development of nosocomial infections. it would be relevant to address this question in larger cohorts of non-selected patients, as well as the impact of platelet transfusions in this setting. conclusion changes in platelet counts were not associated with an increased susceptibility towards icu-acquired infections in non-immunocompromised patients with severe sepsis and septic shock. introduction sepsis is the leading cause of mortality in the intensive care unit (icu) patients despite the progress regarding their care. the immunodeficiency due to sepsis with the consequent profound lymphocyte alterations is now well proven. the objective of this work was to determine the prognostic impact of lymphocytopenia in septic patients in icu. retrospective study including all patients hospitalized for sepsis or septic shock between / / and / / . the sepsis and septic shock definitions were adjusted with the third international consensus definitions for sepsis and septic shock. were excluded from the study patients of onco-hematology. lymphocytopenia was defined as an absolute lymphocyte count less than level of /mm during the first h of hospitalization. the prognostic factors analyzed for the lymphopenic and non lymphopenic patients were in hospital mortality, the occurrence of nosocomial infections and hospital length of stay. results among the patients, aged ± years, patients were with septic shock and patients with sepsis. igsii score and sofa score were respectively ± and ± . four patients were immunocompromised due to hiv infection in one case and an immunosuppressive therapy in cases. lymphocytopenia was observed in patients ( %). twenty-eight patients ( %) died within an average of ± days. it was noted the occurrence of nosocomial infections. the median length of stay was days with extremes of one and days. the lymphopenic patients were comparable to non lymphopenic patients in terms of medical history and severity scores. mortality was comparable between the groups with a rate of % (n = ) in lymphopenic patients and % (n = ) in non-lymphopenic patients (p = . ). the earliness of death was correlated with the duration of lymphopenia (r = . , p = . ). the occurrence of nosocomial infections was not different between the two groups: % (n = ) for lymphopenic and % (n = ) for non lymphopenic patients. the hospital length of stay was not different between the two groups but was correlated with the duration of lymphocytopenia (r = . , p = . ). conclusion lymphocytopenia is frequently found in sepsis. lymphocytopenia was not associated with excess of mortality nor with the subsequent occurrence of infectious complications during the icu stay. his persistence was associated with an earlier death and a more prolonged hospitalization. none. introduction relative adrenal insufficiency (rai) is common in icu patients, particularly during septic shock ( ). it has been shown that the rai also occurs during cardiogenic shock ( ) . septic cardiomyopathy occurs in a significant proportion of septic shock patients. the aim of this study was to evaluate the role of rai on septic cardiomyopathy. patients and methods prospective observational study conducted in the intensive care in one university hospital in france. patients meeting the criteria for septic shock without prior corticosteroid therapy and without chronic heart disease were included. total blood cortisol levels were assessed immediately before (t ) a short corticotropin stimulation test ( . mg iv of tetracosactrin) and and min afterward. Δmax was defined as the difference between the maximal value after the test and t . rai was defined as an inappropriate adrenal response with Δmax < µg/dl and septic cardiomyopathy as the appearance of cardiac systolic dysfunction (left ventricle ejection fraction < %) within the first days of septic shock. we performed a multivariable analysis using backward stepwise logistic regression to identify independent predictors of septic cardiomyopathy. discussion although the definition of rai is not consensual, a threshold of Δmax at µg/dl has been widely used in septic shock, with or without the use of t ( ). the usefulness of substitutive doses of steroids in septic shock is controversial, but many authors assume this treatment has a potential in reversing overt vasoplegia. our data suggest an implication of rai in septic cardiomyopathy. conclusion we found rai to be an independent predictor of septic cardiomyopathy. these findings may suggest a new role for substitutive doses of steroids in the hemodynamic management of septic shock. introduction regional perfusion parameters, like lactate, pyruvate and glycerol, may predict outcome in septic shock patients. continuous venovenous haemofiltration (cvvh) has been considered beneficial in septic shock patients. the aim of our study was to investigate whether cvvh, in comparison to intermittent haemodialysis (ihd), is able to improve regional perfusion in septic shock patients studied by muscle microdialysis. patients and methods it was a prospective, randomized, clinical study, including septic shock patients with acute renal failure, aged over years. patients were randomized to receive either cvvh (n = ) or ihd (n = ) for renal replacement therapy. intermittent haemodialysis was carried out during the first h of the h study period. systemic haemodynamics and interstitial tissue concentrations of lactate, pyruvate, glucose and glycerol were obtained at baseline, , , and h after initiation of renal replacement by using muscle microdialysis. results regarding systemic haemodynamics parameters, cvvh caused a decrease in heart rate in contrast to ihd after h (− ± vs + ± /mn). there were no changes in vasopressor support throughout the -h study period and so systolic blood pressure remained stable in both groups. during the h of all renal replacement therapies there was no significant change in muscle pyruvate and glucose levels. during cvvh muscle lactate decreased constantly, as did muscle glycerol levels. this decrease reaches a significant levels at h for muscle lactate and at h for muscle glycerol (fig. ) . conclusion our results suggest that among septic shok patients, cvvh may improves regional perfusion in comparison with ihd. none. introduction acquired hypernatremia (h-na) is an independent risk of death among icu patients ( ). in the rct "hyper s" study, we compared normal to % hypertonic saline during the first h in patients with septic shock with normal serum na concentration (sna) at baseline. the study was prematurely stopped for potential harmful effect associated with more frequent h-na. we assessed the role of h-na on mortality. patients and methods data are a post hoc analysis of the "hyper s" study database including patients. sna was measured at h , every h for days and then daily until d . study fluids were stopped if sna > or > mmol/l increase over h. mild, moderate, and severe h-na were defined as sna > mmol/l, > mmol/l and > mmol/l, respectively. sna profiles were compared between d survivors and non-survivors. acute kidney injury (aki) was defined by doubling serum creatinine and/or need for dialysis. results patients with available data were analysed. ( %) developed h-na (mild: %, moderate: %, severe: %). no matter the absence or presence and its severity, h-na did not affect mortality ( , , , and %, respectively without, with mild, moderate, and severe h-na, p = . ). sna profiles were similar between survivors and non-survivors (table ) . a sensitivity analysis performed among survivors at d did not change the results. compared to patients without h-na, aki occurred in % of patients with h-n vs % (p = . ), atelectasis in versus % (p = . ) and icu acquired weakness in versus % (p = . ). conclusion hypernatremia occurrence is not associated with an increased risk of morbidity and mortality during hypertonic fluid resuscitation in septic shock. none. introduction guidelines about the moderate hypokalemia treatment (between . mmol/l and . mmol/l) are based on experts estimations, and non-specific ones for patients in the intensive care units (icu). the aim of this study was to evaluate the correction of the hypokalemia in an icu and the compliance of recommendations. materials and methods an observational epidemiological, retrospective and monocentric trial has been realized during a period of months (from january to february ). the study population included hospitalized patients in the icu who have shown a first moderate hypokalemia episode, all cause considered. patients who have presented an acute renal failure with a kdigo (kidney disease: improving global outcomes) score of three the day of their inclusion were excluded. the main primary study endpoint was percent correction of the serum potassium after h. the secondary study endpoints were the incidence rate of moderate hypokalemia and the efficacy about the hypokalemia correction in accordance with the achieved treatment consistent or not with recommendations. results patients had at least one episode of hypokalemia. the incidence rate of the hypokalemia first episode was . %. the study population included patients. igs score was . (± ). patients required mechanical ventilation at the inclusion. the serum potassium was greater than or equal to . mmol/l after h about patients ( . %) (corrected group). at h one patient had a serum potassium higher than mmol/l. the average total potassium was respectively . infusion of potassium and ( . %) patients have been a management compatible with the most common recommendations (input potassium chloride of mmol, use of the enteral administration and lack of continuous intravenous infusion). the percent correction of the hypokalemia after h was respectively of / ( . %) in the group in which recommendations had been respected and of / ( . %) in the other one (p = . ). discussion in our knowledge there are no previous studies that have specifically focused on the correction of the moderate hypokalemia in critically ill patients. in our study the incidence rate of the moderate hypokalemia was lower than data from the literature because we have only considered the first episode of the hypokalemia [ ] . among patients without contraindication to the enteral administration, this one was used in less than half of the cases. % of these patients received potassium with a continuous intravenous infusion and only patients received medical care conform to the guidelines. the medium potassium quantity provided was very lower to the guidelines. only % of the patients have been corrected after h without any difference in the medium potassium quantity which has been provided in relation to the uncorrected group. conclusion only . % of moderate hypokalemia in icu are corrected after h. the intravenous way is considerably used (in % of cases) with a poor return. a wide-ranging study is necessary to determine the best correction modes. none. results patients were included. mean ± sd age was ± years, % were male, mean ± sd saps ii was ± . icu length of stay was ± days and icu mortality rate was %. during the first days in the icu, % of patients received at least one nephrotoxic drug. % of patients received one, % received two, % received three and % received more than three nephrotoxic medications. diuretics, antibiotics and iodinated contrast media were the nephrotoxic drugs most frequently administered to, respectively, , and % of patients. aki (kdigo stage or higher) occurred in % of patients during the first days in icu. the proportion of patients with aki increased with the number of nephrotoxic drugs received: / ( %) of the patients not exposed to nephrotoxic drugs developed aki whereas, respectively, / ( %), / ( %), / ( %) and / ( %) of the patients receiving one, two, three, and more than three nephrotoxic drugs developed aki. the univariate association between the number of nephrotoxic medication and aki persisted in the multivariate analysis adjusted on baseline saps ii score (p < . ). conclusion the significant proportion of patients exposed to nephrotoxic drugs and the observed association with aki warrants further investigation. statistical adjustments for multiple potential confounders is needed in order to assess a potential causal relationship which would lay foundations for interventional studies. none. ( ) the minimal kidney aggression by current monomeric nonionic low-osmolar contrast media, late serum creatinine increase being explained by the occurrence of later (between the th and the nd hour) kidney injury due to critical illness or its therapy or ( ) insufficient sensitivity of early ( h) measurements of this biomarker to detect contrast-associated aki. competing interests partial financial support, no implication in data analysis and interpretation. introduction diabetic ketoacidosis, generally resulting from an absolute deficiency of insulin, is a frequent cause of hospitalization in intensive care unit. recommendations for diagnosis of diabetic ketoacidosis, care and site of admission have been published by the english society of diabetology. icu admission are recommended if one of the following criteria is present: gcs < , systolic arterial pressure (sap) < mmhg, spo < %, ketosis > mmol/l, hco < mmol/l, ph < . , potassium level < . mmol/l or anion gap > mmol/l. however, it is suspected that adhesion to recommendations remains low. in this study, we aimed at describing patients admitted for diabetic ketoacidosis in icu. we looked at adhesion to published recommendations regarding admission and care. we also described metabolic complications and looked for an association between complications and dose of initial insulin therapy. complications hypoglycemia (< . mmol/l) was observed in % of patients within the first h in which % were < . mmol/l. this was and % of patients between and h of icu stay. hypokalemia below . mmol/l happened in % of patients within the first h and in % between and h. neither hypoglycemia nor hypokalemia were correlated with initial insulin bolus or initial dosage of continuous intravenous insulin. hypophosphatemia < . mmol/l was observed in % of patients. discussion in this study, admission to icu was consistent with british recommendations since most patients presented at least one clinical or biological criterion indicating icu admission. arterial blood gas were sampled in the large majority of patients despite consistent data showing that venous blood gas might be sufficient in non-hypoxemic patients. also, initial insulin bolus and sodium bicarbonate perfusion were performed in a significant subset of patients despite absence of convincing data or recommendations supporting their use. finally, significant hypokalemia and hypoglycemia were frequent in these patients. these complications are in theory favored by insulin therapy but we did not observe a correlation between administration of an insulin bolus or the dose of continuous intravenous insulin perfusion. conclusion in this retrospective multicentre study, patients admitted in icu for diabetic ketoacidosis were correctly oriented regarding the british recommendations. metabolic complications (hypoglycemia and hypokalemia) were frequent but not correlated with initial dose of insulin. the appropriate rate for hypernatremia (h-na) correction is unknown. under-correction could be associated with worse outcome. experts recommend a rapid correction of acute (< days) and sever (> mmol/l) h-na with a rate of − mmol/l/h until na < mmol/l ( ). correction should be, therefore, obtained within h. in patients with septic shock resuscitated with iso-or hypertonic saline and who acquired acute severe h-na, we assessed if the correction rate was associated with mortality. patients and methods data are a post hoc analysis of the rct "hyper s" database comparing normal to % saline for h in septic shock. serum na (sna) was measured at h , every h for days and ) . h-na correction rate was more rapid in non-survivors, p = . (table ). over-correction occurred similarly in survivors ( %) and non-survivors ( %). the time to reach sna normalization was shorter in nonsurvivors (p = . ). after adjustment for sapsii and maccabe scores, more rapid correction rate remained significantly associated with mortality: or . ; % ci ( . - . ), p = . . conclusion in the context of acute severe h-na induced by fluid resuscitation, a rapid correction rate might be associated with even aggravated rather than improved mortality. introduction systemic capillary leak syndrome (slcs) is a rare disease characterized by recurrent life-threatening attacks of capillary hyper permeability in the presence of a monoclonal gammopathy (mg). during acute episodes, the leak of fluid and proteins from the intravascular compartment to the interstitium results in clinical signs of both acute hypovolemia and interstitial edema. biological profile is pathognomonic with marked hemoconcentration and paradoxal hypoproteinemia. hypovolemic shock is the classical feature of severe scls attacks. however, beside this typical hemodynamic profile, several case report described myocardial dysfunction during scls attacks. the objectives of this study were to assess frequency, characteristics and outcome of myocardial involvement during severe scls attacks. ( %) mechanical ventilation, ( %) renal replacement therapy, ( %) veno-arterial extracorporeal membrane oxygenation, ( %) intra-aortic balloon pump and ( %) an impella. compartment syndrome occurred in ( %) patients and ( %) died in icu. we then compared the patients with myocardial involvement to the without clinical and biological manifestations were similar in between groups. however, chest pain ( vs %, p = . ), dyspnea ( vs %, p = . ) and respiratory failure ( vs %, p = . ) were more frequent in patients with myocardial involvement than in others. there was no difference between groups regarding treatment received in icu, complication and outcome except for the use of va-ecmo ( . vs %, p = . ). conclusion myocardial involvement seems frequent in patients with severe scls attack, occurring in % of the cases. such patients exhibited classical features of scls attacks. myocardial involvement was responsible for altered lvef or transient ventricular hypertrophy. myocardial dysfunction could be severe, even requiring mechanical circulatory support. scls attacks should be known as a cause of severe reversible myocardial dysfunction and hypertrophy. none. introduction in refractory cardiorespiratory emergencies, ecmo appears a good alternative to conventional treatment. its extracorporeal circuit justifies curative anticoagulation explaining haemorrhagic and thrombotic complications. activated clotting time (act) is empirically and commonly used to assess anticoagulation but with large inter and intraindividual variabilities. in practice, antixa activity dosage is available to approach anticoagulant effect of heparin and is less expensive, but data during ecmo are missing. we sought to demonstrate the lack of correlation between antixa and act in patients under ecmo support. we prospectively include patients supported by ecmo in chu toulouse, france, between / and / for circulatory/respiratory support. anticoagulation was achieved by unfractionated heparin: initial bolus then continuous intravenous infusion ( - iu/h), for antixa target of . - . . concomitant dosing of antixa (laboratory) and act (hemocron ® ) was conducted two times a day on the same sample throughout the ecmo period. relationship between act and antixa was analyzed by spearman correlation (rho). after transformation into categorical variables (obtained target = ; outside the target = ), analyzes were completed by a concordance study (kappa). as recognized on literature act's targets were between and . results patients were included: men ( %), median age yo ( - ). indications were veno-arterial (n = ) and veno-venous ecmo (n = ). ecmo median duration was days (hours to days). spearman correlation test found low and inconsistent correlation between antixa and act (rho spearman < . ). this correlation lack present from the day one, worsens over time. analyzed kappa showed no discrepancy between the areas "targets" of act and antixa confirming the results (table ) . conclusion use of act for ecmo anticoagulation monitoring doesn't seem appropriate and high price probably justifies preferential use of antixa in clinical practice. analyzes of relationships between antixa and bleeding/thrombotic events are needed to confirm the antixa place and its target in these indications. introduction postcardiotomy cardiogenic shock (cs) has an incidence of % to % after routine adult cardiac surgery. in . - . % of cases, an venoarterial extracorporeal life support (va-ecls) is requested. the -month survival rate is . % ( ). survivors may suffer of physical and psychological impairments as well as an alteration of quality of life. this study was designed to assess the outcomes, long-term health- since icu discharge, % of patients reported physical sequelae., ecls-related limb pain occurs in % of patients while paresthesia occurs in % and chronic-tiredness in %. mean karnofsky score was % (table ) . conclusion after va-ecls for postcardiotomy cardiogenic shock longterm physical and psychological sequelae are frequent in survivor discussion interest for fluid management is growing in critical patients. nevertheless, no study has yet investigated its impact in selected patients with cardiogenic shock treated with va ecmo. our study suggested a possible association between fluid overload and mortality but lack the power to confirm these results with multivariate analysis. conclusion fluid management is a key therapy during va ecmo but fluid overload could be associated with worsen outcomes. further studies with larger population are warranted before considering fluid restriction trials. introduction extracorporeal life support (ecls) has taken an important place in the treatment of cardiogenic shock (cs) or refractory cardiac arrest (ca). however, ecls deplore a high mortality rate in the first days raising important ethic and economic consequences. in this context, continuation of support should be reassessed precociously. the aim of this study was the research of prognostic factors of -days mortality, h after ecls implantation for cs or ca. materials and methods all patients undergoing ecls in our tertiary center during a -year period were prospectively included. the ecls were managed with a multidisciplinary protocol based on consensus. clinico-biological data were collected just before and h after ecls implantation. these data were compared between survivors and deceased at month. , cpc score was respectively for patients, for , for . at months, cpc score changed only for the patients with a cpc score at (one died after another suicide attempt, one changed his cpc score to ). in the group without ca (n = ), had normal neurological status at months and at months (one patient died because of a cancer). among these patients, % returned at home and % returned to work. ( %) patients re-attempted suicide in the year. the major risk factor of mortality is the presence of a cardiac arrest on hanging site. all the other factors found to be related to mortality are well known risk factors in cardiac arrest of other origin. in univariate analysis, risk factors of neurological sequelae at months were a cardiac arrest on hanging site (p = . ) an elevated diastolic blood pressure ( vs mmhg; p = . ), a lower initial glasgow score ( vs ; p = . ), and an elevated blood glucose ( . vs . g/l p < . ) at admission in icu. discussion our cohort of self-hanging patients can be divided in two parts: a) patients with ca in the pre-hospital period with a high mortality and a good neurological recovery in / surviving patient, but with a small group; b) patients without ca with a very low mortality and a very good neurological recovery. these results seem to be better than in the most important cohort [ ] published until now in self-hanging patients without ca and not treated by hbot (mortality at . % and . % of poor neurological recovery). conclusion patients surviving a self-attempted hanging who have not presented ca and treated by hbot have mainly a good neurological outcome. randomized control study should be undertaken to confirm hbot effectiveness in that indication. introduction venoarterial extracorporeal membrane oxygenation (va-ecmo) is increasingly used to treat refractory cardiogenic shock or cardiac arrest. acute brain injury (i.e. ischemic stroke, haemorrhage and/or failure to awaken because of diffuse brain injury) may occur in up to % of patients on va-ecmo and is associated with increased mortality and poor functional outcome in survivors. however, early indicators of neurological outcome are lacking in this population. we aimed to assess the prognostic value of early electroencephalography (eeg) alterations during va-ecmo. we conducted a prospective single-center study in the medical icu of a university hospital on consecutive patients cannulated to va-ecmo. a standardized clinical neurological evaluation including the rass score, the gcs score, the full outline of unresponsiveness (four) score and brainstem reflexes was coupled to an intermittent eeg. eeg was recorded as soon as possible within the first h after va-ecmo cannulation. eeg characteristics were analyzed by a neurophysiologist who was blinded to the patient's condition. a severely altered eeg pattern was defined as a predominant delta frequency, discontinuous, unreactive and/or an isoelectric background. the primary endpoint was poor neurological outcome, defined as the composite of death or acute brain injury on neuroimaging within days. data are presented as median (interquartile range) or number (percentage). false-positive rates (fprs, corresponding to -specificity) of poor neurological outcome were calculated for each significant predictor, using an exact binomial % confidence interval (ci). results sixty-nine (age ( - ) years) patients with a sofa score of ( - ) were included. main indications for ecmo were: post cardiac surgery (n = , %), terminal dilated cardiomyopathy (n = , %), and acute myocardial infarction (n = , %). cardiac arrest before ecmo cannulation was noted in ( %) patients. eeg was recorded ( - ) days after va-ecmo cannulation and ( %) patients were sedated at time of eeg. at day , ( %) had a poor outcome (n = deaths and n = patients alive with acute brain injury). in univariate analysis, a lower rass score (p = . ), a lower four score (p = . ), a lower score on the motor component of the glasgow coma scale (p = . ), and a lack of cough reflex (p = . ) at the time of eeg were significantly associated with a poor outcome. a severely impaired eeg pattern or presence of a discontinuous background activity were also associated with a poor outcome (p = . and p = . , respectively). indicators of poor neurologic outcome are presented in the table . among all parameters, a discontinuous background activity was the only variable that constantly predicted poor outcome (false-positive poor outcome prediction rate of %, % ci - %). conclusion early intermittent eeg has a strong prognostic value for sedated patients on va-ecmo. presence of a discontinuous eeg background activity seems to be more accurate than clinical alterations to predict a bad neurologic outcome at days. none. table ). it was not found a significant association of ctp to mortality ( % in the case group and % in control group, p = . ). other factors that increased mortality were coma, seizures, shock, oedema, cellularity in csf > units/mm . otherwise, the ventilation length was prolonged with ctp group ( . vs . days, p = . ) and neurological sequels namely the epilepsy was more frequent with the group ctp: ( vs %, p = . ). conclusion the occurrence of ctp on bacterial meningitis was significantly associated with ct scan lesions which seems to be an association be in both directions. also, the positive culture predisposed more to the ctp. mortality was higher with the presence of ctp but without real significance. the ctp was a factor that extends the ventilation time and exposed to the post infectious epilepsy. introduction acute bacterial meningitis requires rapid triage and therapeutic decision-making. the aim of this study was to assess the overall ability of a point-of-care glucometer to determine bacterial infection in cerebrospinal fluid (csf). we performed a prospective, observational study. we included patients for whom an analysis of csf was indicated by the physician in charge with blood sampling performed for glucose concentration measurement within h. we simultaneously measured the glucose concentrations in csf and blood using a central laboratory and point-of-care glucometer. the diagnosis of bacterial meningitis was determined by two physicians after reviewing the complete medical chart. we compared csf and blood glucose concentrations and csf/blood glucose ratios obtained at the bed-side with a glucometer versus those obtained by the central laboratory. we determined the performance characteristics of the csf/blood glucose ratio provided by a glucometer to detect bacterial infection in the csf immediately after csf sampling. conclusion we demonstrated that the csf/blood glucose ratio measured by a glucometer can serve as a clinical decision support tool for the early detection of csf with a high probability of bacterial infection. this costless point-of-care method has the potential to expedite medical decision-making for the triage of adult patients with suspected meningitis in the emergency department immediately after lumbar puncture. none. introduction cardiac arrest remains a frequent cause of admission in intensive care unit. a majority of patients will die during their hospital stay mainly from consequences of hypoxic-ischemic brain injury after a decision of withdrawal of life sustaining therapy support by a prediction of poor outcome. the reliability of prognostication is crucial, but is still a difficult and uncertain exercise. eeg is the most widely used prognostic tool to support a clinical examination and is accessible in most hospitals. it is recommended for both prognostication and ruling out subclinical seizures. there is no high-level evidence for predicting poor prognosis using eeg because of the wide variety of classification systems used and the interrater variability. our objective is to assess the prognostic value of simple eeg features based on the recent american clinical neurophysiology society (acns) standardized classification and to study the interrater variability. we conducted a retrospective monocentric observational study in a bed medical intensive care unit of the university hospital la timone, marseille, france. all patients aged of more than year-old admitted for a resuscitated cardiac arrest between november and july who underwent therapeutic hypothermia and a full multimodal prognostic evaluation including a eeg were included in the study. outcome was classified according to the cerebral performance category score measured at day . unfavorable outcome was defined as death (cpc ), persistent vegetative state (cpc ), or severe neurological disability (cpc ). favorable outcome was defined as moderate neurological disability (cpc ), or no disability (cpc ). eeg was performed in all patients still comatose after rewarming between and h after admission and after discontinuation of sedation. eeg interpretation was made by independent senior neurophysiologists, blind to the outcome. eeg features are based on the latest acns classification. for each eeg feature, sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv) for predicting an unfavorable outcome were calculated. results during the study period, cardiac arrest were admitted of which patients went through a full neurologic evaluation and were finally included in the study. according to neurological outcome, % had a favorable evolution, and % had an unfavorable outcome. the presence of burst suppression, and epileptiform activity was constantly associated with an unfavorable prognostic with a % specificity and % false positive. a non-reactive eeg is strongly associated with an unfavorable evolution with a % specificity and % false positive. other features including periodic or rhythmic patterns and low voltage were inconstantly associated with unfavorable outcome. kappa score for all eeg feature was slight or fair and always under . . discussion this study allowed us to identify a homogenous cohort of comatose patient after cardiac arrest who underwent therapeutic hypothermia. we identified simple eeg features based on the new classification of the acns constantly associated with unfavorable outcome. these features must be known by intensivists to better integrate eeg in the multimodal evaluation of neurological prognostic. there is important interrater variability that must lead to caution and to always use multimodal approach to prognostic an unfavorable outcome. conclusion bedside eeg is an excellent tool for predicting outcome of post-anoxic coma through simple eeg features. burst suppression, epileptiform activity and non-reactive eeg are strongly associated to neurological outcome after cardiac arrest. however, the interrater variability emphasize the need of being well trained for the standardized methods of evaluating eeg parameters. introduction emergent reintubation is a well-known risk of laryngotracheal trauma and of ventilatory acquired pneumonia. to precisely define its risk before extubation for each patient is a part of quality of care in intensive care units. none of these consecutive children representative of picu activity has been reintubated. the coming prospective muticentric study which aims to validate alt in childhood must precisely define this criteria of evaluation. conclusion the different methods of alt are feasible in real clinical conditions in picu. because of the increasing use of cuffed etts in a wide variation of patients with different body weight, the best alt to use at the bedside must be definitively validated in this population. introduction prolonged mechanical ventilation (pmv) and chronic mechanical ventilation (cmv) in neonates is associated with a high morbidity and mortality. the objective of the study is to identify, among the patients with pmv, those that evolved to cmv, as well as the adverse respiratory, neurological and feeding sequelae. we conducted a retrospective study of the last years at the chu sainte-justine (montreal, canada). chart review included patients with pmv (≥ days) using the paediatric definition adapted from the namdrc consensus conference ( ) . demographic and clinical data, including follow-up at and months corrected age, was collected for each included patient. the evolution of pmv neonates with cmv (≥ days) and without ( - days) was compared. we identified neonates that met criteria for pmv. patients born between and (n = , % of the cohort) were analyzed. around half of the patients ( - patients a year) are transferred from the neonatal unit to the paediatric intensive care unit. in our center, they represent around % of total admissions, but their length of stay is among the longest. among these newborns, % were preterm (n = ) with % (n = ) born before weeks gestation. of all patients with a malformation ( %, n = ), had a thoracoabdominal anomaly and had congenital heart disease. thirty-six patients had cmv with mean ventilation time of days (range - days). survival at months corrected age was % ( / ) in the pmv group and % ( / ) in the cmv group. at months corrected age, % of patients were dependent on artificial enteral feeding (nasogastric tube or gastrostomy), with % in the pmv group and % in the cmv group. nine percent of patients had oxygen supplementation ( patients in the pmv group and in the cmv group), and % were mechanically ventilated. ten percent of patients had a tracheostomy ( patients in the pmv group and in the cmv group). discussion neonates with cmv have more sequelae. their rapid identification (at days of ventilation) is essential to implement multidisciplinary development care in order to minimize neurodevelopment impairment. conclusion most newborns in our pmv cohort have a congenital malformation. survival at months corrected age appears equivalent in both pmv and cmv group. artificial enteral feeding is more frequent in the cmv group and most patients have no respiratory support at months corrected age. none. the value of pressures and volumes in assessing the fluid responsiveness depend on the systolic cardiac function in adult ( ). we have studied the relative value of static filling volume and pressure to predict the fluid responsiveness, according to systolic cardiac function in children during acute circulatory failure. patients and methods patients under years old with an acute circulatory failure of two intensive care units during a year period of inclusion were analyzed. an exhaustive cardiac echography was performed initially (indexed end-diastolic volume (edvi) and e/e' from transmitral and tissue doppler were recorded), and the stroke volume index (svi) was measured before and after a fluid challenge (a ml/ kg of crystalloid over min results twenty-five children with acute circulatory failure were included. fluid responsiveness occurred in of the fluid loading events with low lvef, and in of the fluid loading events with normal lvef. pressure approach: for low and normal lvef, the auc-roc for fluid responsiveness was respectively . (ci . - )/ . ( . - ) for a e/e' .the best thresholds of e/e' in low lvef was . with a sensitivity of (ci - ) % and a specificity of (ci - ) %. for low and normal lvef auc roc was respectively . (ci . - . )/ . (ci . - . ) for the pvc. volume approach: for low and normal lvef, the auc-roc for fluid responsiveness was respectively . (ci - ) and . ( . - ). the best thresholds in normal lvef was an edvi below ml/m wit a specificity of (ci - ) and a sensitivity of (ci - ) %. discussion our study shows a variation of the diagnostic value of e/e' and edvi according to the left ventricular systolic function. therefore, the systolic function should be taken into account to analysed the e/e' and edvi value. few preload dependency markers are validated in children and none for children in spontaneous ventilation ( ) . our study suffers from a lack of power that calls into question the validity of our results. another limitation is that both approaches with volume and pressure are not very discriminant as it is known for static value in adults. our study illustrates that, on a pressure-volume curve, when the cardiac inotropism is reduced, the filling of the left ventricle is moved to the up and right of the curvilinear diastolic function curve. therefore, pressure variations are larger than volume variations. these values should be monitored on a larger scale to define their exact diagnostic value. conclusion static pvc value is a low preload-dependency surrogate. when lvef is low a pressure evaluation based approach seems more accurate. when lvef is normal a volume evaluation based approach seems informative as predicted by the slope of the end diastolic pressure volume curve. those both static approaches remain of poor diagnosis accuracy. introduction acute viral bronchiolitis is a primary cause of respiratory distress in paediatric intensive care unit (icu). prone position (pp) is commonly used in neonates to improve respiratory mechanics and has been found beneficial to adult patients with acute respiratory distress syndrome. we aimed to evaluate the effect of pp on work of breathing as compared to supine position (sp) in children with severe bronchiolitis requiring non-invasive ventilation. the protocol was approved by our irb ( -a - ). fourteen infants ( boys) with median age days [firstthird quartiles - ] with severe bronchiolitis requiring cpap were included after written informed consent. children were investigated in pp and sp each applied for h in a random order with a washout period of min between them. level of cpap was set at cmh o in both conditions. oesophageal pressure probe was inserted orally (cto- pressure transducer, gaeltec, scotland) to measure oesophageal pressure. flow and airway pressure (pmo in fig. ) were simultanuously recorded using a neurovent data acquisition system (neurovent inc, toronto, canada). one hundred breaths were analyzed in each condition, in which work of breathing was estimated from oesophageal pressure-time product (ptpes) and oesophageal swings (fig. ). data were expressed as median (first-third quartiles) and compared by using the wilcoxon two-sample paired sign test. a p-value below . was considered significant. . the edtb contains data from ventilated patients (invasively and non-invasively) and details concerning ionotropic and sedative treatment during picu courses. discussion as far as we know, this edtb is currently the only one as exhaustive available in picu worldwide. after almost years of multidisciplinary collaboration, we are able to collect many useful physiological, therapeutic and medical data in an ongoing edtb. although many concerns remain concerning data validation, organisation and exploitation, this edtb already contribute to the development of clinical decision support systems and virtual patient validation and we create international collaborations to further develop these tools. three research protocols using the database are ongoing including: validation of a neuromonitoring clinical decision support system, validation of a cardio-respiratory simulator, developement and validation of the automatic diagnosis of pediatric acute respiratory distress syndrome and development of spo forecast using artificial neuronal network. conclusion thanks to informatics and electronic devices improvement, data gathering in intensive care units has empowered. we hope that our work in picu will encourage other teams on the way of data gathering, in order to build an international picu edtb in a close future. none. introduction severe trauma is rare in the pediatric setting ( % of all trauma in france). however, its morbidity and mortality remain high, in relation to brain injury. pediatric traumatic brain injury (tbi) prehospital care is challenging for non-pediatric retrieval teams. though, we disseminated pediatric tbi pre-hospital care regional guidelines and thereafter intended to assess severe pediatric trauma pre-hospital care and secondary cerebral insults control. we conducted a retrospective study in a single pediatric trauma center. children admitted in emergency room with severe trauma and moderate to severe tbi (glasgow coma scale ≤ ) from june to march were included. pre-hospital and hospital data regarding primary care, equipment, medications and secondary cerebral insults control (i.e. blood pressure, oxygenation, co level, temperature, glycemia) were collected from medical files. two pediatric transport team experts assessed the quality of pre-hospital care, based on two major endpoints. results twenty-nine files were analyzed. median iss was . all the children had been referred directly from the trauma scene to the pediatric trauma center. they were all intubated in the prehospital setting, ( . %) presented with spo < % before or at emergency room admission, and ( . %) presented with a pco > mmhg at admission. at least one peripheral catheter was inserted in all the children. mean total fluid bolus was . ml/kg (± ). nor-epinephrine was administered in ( %) children. mean blood pressure was below age threshold in ( %) children during transport or at admission. an intracranial hypertension treatment (apart from sedation) was delivered in ( %) children before admission. body temperature was monitored in patients and were hypothermic at emergency room admission. experts concluded on sub-optimal care in children: major endpoint was "respiratory care", "hemodynamic care" and "neurologic care" in , and patients respectively. discussion on this small series, we showed pre-hospital sub-optimal care regarding secondary cerebral insults control, especially regarding co level, blood pressure and body temperature. our results will help to design new care improvement strategies (e.g. sedation, fluid bolus and ventilation optimization, early use of vasoactive drugs, systematic body temperature monitoring…). conclusion data on pre-hospital secondary cerebral insults care are rare in the pediatric setting. based on our results, we aim to improve quality of care of children presenting with traumatic brain injury, and to reduce its morbidity and mortality. introduction unsuccessful extubation from mechanical ventilation increases mortality and morbidity. to reduce the extubation failures in our intensive care unit we used a mechanical ventilator weaning protocol, based on published data. during the first part of the study, risk factors and incidence of extubation failure were first described. afterwards in the second part, our mechanical ventilator weaning protocol was tested to determined its efficiency regarding the extubation failure. patients and methods a monocentric and observational study, was first conducted. we included children aged from birth to old, during a period of months and collected for each patient their medical history, intubation and extubation parameters, and existing events of extubation failure or extubation complication. the second part of the study was prospective, we include patients extubated by applying our mechanical ventilator weaning protocol. results average duration of mechanical ventilation was . h in the first part of the study. using a univariate analysis, duration of mechanical ventilation was a risk factor of extubation failure with an average duration of . discussion our study confirms published data about extubation failure risk factor like duration of intubation, chronic respiratory affection, history of previous intubation, and the administration of benzodiazepine. it is the first pediatric study that shows a reduction of extubation failure by using a specific mechanical ventilator weaning protocol. the mean bias of our its retrospective and prospective character. conclusion our study shows the interest of a mechanical ventilator weaning protocol to reduce the incidence of extubation failure. we currently continue the apply our protocol to include more patients in order to confirm our results. stroke of the child is formidable though it is ten times rarer than in adults, but this scarcity can have adverse consequences on the speed and quality of the management and the consequences on later psychomotor development. our goal is to describe the clinical and therapeutic aspects of these pediatric stroke while bringing our experience. patients and methods retrospective study of cases of children hospitalized in general intensive care unit to the pediatric hospital canastel oran for stroke during the period from january to january . the clinical, etiological, para clinical, and scalable were studied and transcribed on a standard electronic form.all patients had a brain ct. magnetic resonance imaging(mri) was possible in patients for lack of availability of the technical facilities during the study. results ten cases were selected. the mean age was months ( month to years), % are male, patients had a history of chd like tetralogy of fallot and complicated bronchiolitis myocarditis, one patient had a history of petechial purpura, other was a factor deficiency, headache history was noted in patients, and patients with no particular antecedent was found. all patients arrived comatose / score on the scale of glasgow, isochores reactive pupils with a motor deficit of hémicorps, patients have degraded their neurological score with onset of clinical signs of hypertension intra cranial namely anisocoria and hypertension requiring osmotherapy, sedation and mechanical ventilation with an average duration of - day. o child arrived brain dead, patients had generalized tonic-clonic seizures which yielded after taking a benzodiazepine (diazepam) and phenobarbital (like gardenal). cerebral ct was performed in all cases and could we revealed the nature of the stroke hemorrhagic in cases and ischemic stroke in cases. two patients have benefited from an mri that found a thrombosis of the artery internal carotid right sylvian. besides symptomatic treatment, treatment was initiated based on the type of stroke, patients received low molecular weight heparin (lmwh) at . ml/kg in addition to symptomatic treatment, patients received vitamin k. four patients died in an array of autonomic disorders and evolved favorably and six patients were transferred to a pediatric unit. the average length of stay in icu was . days ( - days). discussion the mortality rate is important since no specialized center for children, and difficulty especially in the diagnostic imaging field while suspected stroke should be confirmed by imaging and the diagnostic delay. which is due to a poor assessment of the initial situation in half of the cases by the parents, the other half by the swiss magazine consulté.une doctor showed that in a study in % of children with stroke, this diagnosis was not primarily discussed and that in % of cases the cause of the stroke was poorly evaluated [ ] . heart disease certainly represent the second most important risk factor. a collaboration of a team must be multidisciplinary, death has affected mostly older children whose age is between and years, who have a hemorrhagic stroke against by infants who have an ischemic stroke have evolved and oriented they exceed the acute phase to pediatric services for further investigation and monitoring. conclusion the child may also be having a stroke, which usually reaches the elderly. this justifies a good knowledge of this disease, and multiply the initial management efforts to reduce mortality and improve prognosis. anwar armel , benqqa anas , samira kalouch , khalid yaqini , aziz chlilek introduction nosocomial infections are a main problem for public health for their cost as well as for the morbidity and mortality they generate. they are particularly common in intensive care units due to patient's lower defenses and of invasive procedures proliferation. work's purpose: • determine the epidemiology of bacterial noso-comiales infections (ibn) in the medico-surgical pediatric intensive care department of children's university hospital of casablanca. • to identify factors associated with these infections. we led a retrospective study of hospitalized patients, spending more than h in medical-surgical pediatric intensive care department, at the university hospital ibn rochd of casablanca, over a period of months from january to december . results during the studied period, patients were admitted at intensive care with a stay of more than h. thirty episodes of inb were recorded. the incidence rate was . % and the incidence density was . % per hospitalization's days. the admission average age was . ± -month starting from month to years with a male predominance ( %). most of admissions ( %) was related to medical background, . % received from other hospital department. furthermore, % of the patients received prior antibiotics, usually prescribed before icu admission. invasive procedures (intubation, central catheterization) were used in . % of patients, vvp only in . %, tracheotomy in . and . % had received surgery. gram-negative bacilli (bgn) were isolated for a lot of patients, dominated by acinetobacter baumannii. these bacteria were isolated throughout the study year. risk factors analysis underlined that the presence of invasive procedures enhances in risk, that is central venous catheter and the need for mechanical ventilation. conclusion nosocomial bacterial infections are dominated by pneumonia and central catheter infections, and are mainly due to bgn. the factors associated with these infections were identified. the guillain-barré syndrome (gbs) is the most common cause of acute flaccid paralysis in children since the acute anterior poliomyelitis eradication. few studies have been held on the topic and knowledge of gbs in children, although it is recognized that the etiologic mechanisms, and clinicobiological background, are the same as in adults, prognosis remains different. our work's aim is to study this disease's mortality factors of children hospitalized in pediatric intensive care. patients and methods it is a retrospective, descriptive, mono centric study to review patients with gbs between january and december and hospitalized at pediatric intensive care department of abderrahimharouchi hospital of casablanca. the used software is spss . to compare the bivariate variables, we used the khi test, and to compare quantitative variables, the anova to factor test was used. the level of significance was fixed at % with % confidence interval. the disease was predominant in male with a sex ratio of . men/women. after a prodromal event, usually infectious ( . %) and a free interval of days on average to start motor disorders. these are of two types: either a hypo or areflectic flaccid paralysis of the lower limbs ( . %) of ascending evolution in . % of the cases. either flaccid tetraplegia or hypo areflectic, ( . %). ventilation was required in . % of the cases, and specific treatments based on immunoglobulins were administered in . % of the cases. death's rate is still high ( . %) and mainly due to hospitalization complications. in our study respiratory disease was noted in . % of the cases, also other signs of serious illness such as swallowing disorders ( . %) and autonomic disorders ( . %) also noted what led to management in intensive care for all our patients. these patients study allowed to identify some mortality prognosis factors of the disease in intensive care units (such as male gender, ig administration duration, the occurrence of autonomic disorders like blood pressure instability), the most discriminating remains the occurrence of nosocomial infections. conclusion it must be underlined, that in view of our strict inclusion criteria, focusing only on patients admitted at intensive care and of the relatively small sample size ( cases), our results must be qualified and must be enhanced by additional and more varied studies to better understand this disease in children. introduction early surgical treatment is recommended for refractory intracranial hypertension (htic) in children to improve vital and functional prognoses, whether traumatic or vascular cause. the main objective of this study was to compare the mortality and morbidity of children with severe intracranial hypertension after severe head trauma (tc) or due to vascular cause after decompressive craniectomy (dc) or medical therapy alone. the secondary objective was to identify the initial severity factors associated with higher mortality. patients and methods a retrospective study was performed with data collected from patients aged under years-old admitted to our pediatric intensive care unit for severe intracranial hypertension of traumatic or vascular cause, between january and january . they were divided into groups: patients who received medical therapy alone and those treated with decompressive craniectomy after optimal medical management. results a total of children were included. among them, were treated with dc ( htic of vascular cause and htic of traumatic cause), and were supported by medical means only ( htic of vascular cause and htic of traumatic cause). in the population "traumatic intracranial hypertension", we note that children in the "dc" subgroup are more often in mydriasis upon arrival (p = . ) than in the subgroup treated medically. in this same population, children in the "dc" subgroup received higher doses of mida-zolam (p = . ), of mannitol (p = . ) and hypertonic saline (p = . ) than in the other subgroup. in the population "vascular intracranial hypertension" the two subgroups were comparable. in the case of traumatic intracranial hypertension, mortality rate in the "dc" subgroup was . % against . % for children treated medically (p = . ); "dc" children had more metabolic complications such as hypernatremia than "not dc" children, p = . . mortality rate in the «vascular intracranial hypertension» group was % for children treated with decompressive craniectomy, and . % for children treated medically alone (p = . ). patients treated surgically in the «vascular intracranial hypertension» group had longer overall stays (p = . ) and longer icu stays (p = . ). popc score (pediatric overall performance category) upon discharge for children with intracranial hypertension of traumatic cause treated with decompressive craniectomy was . ± . against . ± . among children treated medically, p = . . in "dc" children with intracranial hypertension of vascular cause, popc upon hospital discharge was . ± . against . ± . among non-operated children, p = . . the schooling rate was higher among children treated medically for intracranial hypertension of traumatic cause, p = . . the severity factors related with higher mortality identified in the population "traumatic intracranial hypertension" were mydriasis upon admission, a pim score higher and a lower temperature (< . °); the latter being the only factor identified for htic of vascular cause. in the case of traumatic intracranial hypertension, icp monitoring in survivors was . % against . % in children died, with no significant difference. in the population "vascular intracranial hypertension", all the patients who died had not been monitoring pic. discussion the severity factors related with higher mortality identified in the population "traumatic intracranial hypertension" were mydriasis upon admission, a pim score higher and a lower temperature (< . °); the latter being the only factor identified for htic of vascular cause. other studies have related other severity factors as initial glasgow scale, tardive decompressive craniectomy. conclusion decompressive craniectomy doesn't seem to improve the mortality rate or the outcome in patients with hypertension of traumatic cause in our study but the dc traumatic subgroup was more serious than the subgroup treated medically. in children with refractory intracranial hypertension of vascular cause dc significantly improves survival and outcome. further studies are needed to clarify the role of decompressive craniectomy and its timing in the therapeutic management of refractory intracranial hypertension. introduction shortage of heart grafts is a major problem, leading to a significant mortality rate in the national waiting list, essentially for young children with low weight. the potential paediatric brain-dead donors often have myocardial dysfunction (md), which seems to be reversible. the aim of this study is to assess prevalence, causes and consequences of md when the potential paediatric donors are taken over, up to multi-organ retrieval, and the evolution after cardiac transplantation. materials and methods this observational, monocentric, retrospective study included all brain-dead children aged - years old, who had their myocardial function assessed through a cardiac ultrasound performed by a cardiologist and identified from to . all adult patients and those who didn't undergo a cardiac ultrasound were excluded. md was defined as an lvef ≤ % with or without abnormal segmented cinetic parameters. the main evaluation criteria was the prevalence of md in potential identified donors. the secondary evaluation criteria were the causes and consequences of md on heart retrieval and the origin of this md. results out of included patients, had md. prevalence of md was of %. there was no significant difference between groups regarding aetiology of brain death nor administration of catecholamines. having a cardiopulmonary arrest during intensive care unit stay was associated with a significant risk of presenting a md (p = . ). having a md had no consequences on organ retrieval in general (p = . ), but was significantly associated with a decrease in heart retrieval opportunities (p = . ). the cause of heart grafts refusal was a poor ventricular function in % of cases ( cases out of ). the cause for non-retrieval was parental refusal in one-third of cases. evolution of the cardiac grafts was favorable in cases on , one transplanted patient died (from a non-cardiac cause) and patient was lost to follow up. conclusion md in paediatric brain-dead patients has direct consequences on heart retrieval and transplantation, and otherwise, organ shortage is a major ongoing problem. a better transplant management regarding hemodynamics (with the use of a protocol) could increase the number of heart transplants, especially in small children, and reduce mortality rate in national waiting list. the prone positioning (pp) is a strategy widely used in the treatment of severe forms of acute respiratory distress syndrome (ards) in adults. its early use significantly reduces mortality ( ). however, the studies do not strongly demonstrate its prognostic impact in pediatric ards. the aim of this study was to describe the prone positioning practices in the french-speaking pediatric intensive care units (picu). patients and methods this survey was conducted by email questionnaire to pediatric intensivists belonging to the french society of intensive care medicine and the french-speaking group of pediatric intensive care and emergency medicine. it was conducted from february to may . the survey was addressed to doctors, nurses, physiotherapists practicing in picu. it included questions about indications, contraindications, techniques and medical devices used, and complications. results one hundred and three persons answered ( doctors and nurses) which work in french hospitals and canadian hospital. sixty-eight percent of interviewed persons have more than years experience and % of them treat each year more than children ards. only % of the picu have a pp medical protocol. fifty percent of interviewed persons frequently use pp for the medical care of ards and % systematically use it. thirty-six percent begin pp at the early phase of ards during conventional ventilation, while % before the introduction of unconventional ventilatory strategies (ohf); only % use it after the respiratory failure unless unconventional ventilatory strategies. seventy-three percent report that pp is used with prolonged periods (> h/day), % with short periods (< h/day) and % with very long periods (> h/day). regarding the weaning criteria, most of interviewed persons seem to use multiple and combinated criteria: % use hypoxemia severity parameters (pao /fio , pao , sao ), % use the oxygen level (fio ) and % use the mechanical ventilation parameters (peep, p max, p plate). finally, despite a low level of scientific evidence in children, % of the persons gave a strong recommendation for pp as standard care in severe pediatric ards. see fig. . the survey confirmed the widely use of pp in pediatric ards. however, no specific protocol is avalaible in most of the picu. the timing of the pp beginning can be different according to children, early and prior to use of the conventional ventilation strategy in most cases. the duration of pp seems more consensual. most of the centers use extended periods longer than h/day. these results are close to guérin et al. advocating a duration > h/day. finally, the weaning is a great issue and depends on multiple criteria. in guerin et al. ( ) pp was interrupted if one of the following criteria were present: pao / fio ≥ mmhg, with peep of ≤ cm of water and a fio of ≤ . ; decreased pao /fio than %, compared to compared to the supine position, or the occurrence of complications. no study has validated pp weaning criteria during pediatric ards. conclusion the prone positioning is a strategy commonly used in pediatric intensive care units for the severe pediatric ards. the criterias of implementation and timing are variable, as well as the weaning criterias. more pediatric multicenter randomized studies will be necessary to confirm the benefits of pp in pediatric ards and to define clear weaning criteria. introduction allogeneic hematopoietic stem cell transplantation (hsct) recipients have profound defects in every immunity compartments that can lead to severe opportunistic infections (oi). % of hsct patients require admission to the icu because of diverse infectious or non-infectious complications with dismal outcomes. oi specific course in this population has not been described previously and the management of these infections may be a concern. the aim of this study was to investigate risk factors, management and outcomes of io in hsct recipients admitted to the icu. patients and methods this was a retrospective ( - ) single center study of patients admitted to icu after an allogeneic hsct. patients provided written informed consent according to helsinki declaration. data regarding the transplant, infections and life sustaining therapy use were analyzed. oi were considered if present at the time or during icu admission. results hundred and ninety-four patients (pt) were included. median age was [ ; ] years, . % were males. reason for transplantation was acute leukemia in ( %) pt and the hematological condition was still in complete remission at icu admission in % of patients. ( %) and ( %) had received a myeloablative conditioning regimen and anti-thymoglobulin serum respectively. % had acute graft versus host disease over grade at icu admission. oi was documented in patients ( %). an invasive fungal infection (ifi) was found in pt owing to mucormucosis, trichosporon septicemia and invasive aspergillosis ( possible, probable and proven according to eortc criteria). serum galactomannane antigen was positive in ( %). median time from transplantation and icu admission to ifi diagnosis was respectively [ ; ] and − [− ; ] days. lung was involved in % and patients with aspergillosis were admitted to the icu for acute respiratory failure in % (vs. % for others p = . ). they did not required invasive ventilation more frequently ( vs. % p = . ). and % required vasopressors and renal replacement therapy with no difference as compared to others. median icu length was [ ; ] days. demographic, stem cell source, and donor type were not associated with ifi occurrence in this population. however / had received a total body irradiation ( vs. % p = . ). ifi occurrence was not associated with icu or day mortality ( vs. % p = . and vs. % p = . respectively). a viral infection was found in pt owing to cmv, adenovirus, hsv and vrs infections. analyses were focused on cmv reactivation. median time from transplantation and icu admission to cmv reactivation was respectively [ ; ] and − [− ; − ] days. reactivation was mainly positive blood pcr but pt had cmv colitis. a preemptive treatment was started on the same day in median and lasts [ ; ] days. patients with cmv reactivation had more frequently multiple organ failure ( vs. % p = . ) and higher icu admission sofa score ( [ ; ] vs. [ ] [ ] [ ] [ ] [ ] [ ] p = . ). they trend to have higher admission creatinine serum level ( [ ; ] vs. [ ; ] umol/l, p = . ) and more frequently required emergency renal replacement therapy ( vs. % p = . ) mechanical ventilation ( vs. % p = . ) and vasopressors ( vs. % p = . ). median icu length was [ ; ] days and comparable to others. demographic, stem cell source, conditioning regimen and donor type were not associated with cmv occurrence. cmv reactivation was not significantly associated with icu or day mortality ( vs. % p = . and vs. % p = . respectively). conclusion oi was found in % of allogeneic hsct recipients admitted to the icu. ifi were mainly responsible for respiratory distress and cmv associated to multiple organ failure. non-invasive diagnostic tests were positives in a majority of these patients. in this cohort, io treatment was started quickly after the diagnostic and we did not find an association with mortality. intensivists should always consider oi in their diagnostic panel in this specific population. introduction over the last two decades, targeted therapies in patients with solid tumors have both increased their length of survival and significantly altered their immune functions. however, data on opportunistic infections in this setting remain scarce. in this systematic review, we sought to identify published cases of opportunistic infections in patients with solid tumors, with a special interest on clinical findings, trends over time and outcomes. materials and methods we performed a search of medical subject headings (mesh) on pubmed using the words pneumonia pneumocystis (pcp), invasive aspergillosis (ia), histoplasma, mucor, geotrichum, cryptococcus, coccidioidomycosis combined with the mesh term neoplasms (breast, lung, ovarian, urologic gastrointestinal, digestive system, abdominal, brain, carcinoid tumor, sarcoma, testicular, seminoma). we identify published cases of opportunistic infections in non hiv patients with solid tumors between / / and / / included. results regarding pneumocystis jirovecii pneumonia, cases could be identified. there were men and women, aged of . ( - ) years. underlying tumors were chiefly brain neoplasms (n = , %), lung neoplasms (n = , %) and breast neoplasms (n = , %). at the time of pneumocystis pneumonia onset, patients ( %) had a history of chemotherapy, ( %) had received long term or high dose steroids, and ( %) had an history of biotherapy targeting the malignancy. of note, patients ( %) had received only chemotherapy, ( %) had received steroids alone, ( %) everolimus therapy alone and ( %) received none of these treatments. regarding invasive aspergillosis cases could be identified. mean age was . ( - ) and ( %) were men. solid tumors associated with invasive aspergillosis were primarily lung neoplasms (n = , %) and brain neoplasms (n = , %). at aspergillosis onset, ( %) patients had a history of chemotherapy, ( %) were receiving long term or high dose steroids and ( %) had received targeted therapy. fourteen ( %) patients had received only chemotherapy, ( %) only steroids, and ( . %) had received targeted therapy alone. for both infection, there was a trend for a higher number of reported cases throughout the studied period. conclusion this systematic review provides objective data showing that an increased proportion of patients with solid tumors present with opportunistic infections. we are convinced that it is a clinically relevant but still neglected problem. selected oncologic population may be becoming eligible for antimicrobial prophylaxis against pneumocystis or aspergillus. care unit of strasbourg in france. patients were included only if they are non-immunocompromised according to the european organisation for research and treatment of cancer (eortc). invasive aspergillosis was defined as an association of microbiological evidence, a radiological imaging and a clinical context. results eighteen patients ( males) were identified during the study period. the median of igs ii was . (interquartile range (irq), . - . ). ninety-four percent was under mechanical ventilation. fourteen ( %) patients were suffering from liver failure. among liver failure, twelve ( %) were beforehand suffering from cirrhosis. the median meld score was (interquartile range (irq), - ). sixty-four percent of aspergillosis were due to aspergillosis fumigatus. hundred percent were pulmonary aspergillosis. fifty-six percent of aspergillosis were associated with bacterial pneumonia. the mortality rate at the date of the latest news (an average of years) was seventytwo percent. discussion invasive aspergillosis is not exceptional in the non-immunocompromised patient especially in patient developing liver failure. an active research of colonization/infection with aspergillus in these patients remain to be discussed. conclusion invasive aspergillosis in icu has a poor prognosis. the liver failure seems to be the most important risk factor in non-immunocompromised patients according eorct criteria. introduction chest wall elastance (ecw) has been found to increase in prone (pp) as compared to supine position (sp) in ards patients [ ] . this makes respiratory system elastance (ers) not reflecting lung elastance (el). little is known about the changes of ecw, el and lung resistance (rl) when moving the patient from the sp to the pp via the lateral position (lp). the goal of present study was to measure ecw, el and rl in ards patients in sp, lp and pp during the proning procedure. patients and methods it was a prospective, single-center, controlled study. ards patients intubated, sedated and paralyzed with pao /fio ratio < mmhg, peep ≥ cmh and an indication of pp were included. mechanical ventilation was delivered in volume controlled mode with constant flow inflation and end-inspiratory pause . s included into the inspiratory time. ventilator settings were unaltered during the procedure. an esophageal balloon catheter (nutrivent device) was used for esophageal pressure (pes) measurement. pressure at the airway opening (pao) and airflow were measured by fleish pneumotachograph proximal to endotracheal tube and upstream heat and moisture exchanger. pao, pes and airflow were continuously measured during min in sp, then during min in lp and min in pp. the side for the lateralization was that selected by routine practice (in the opposite side from central venous line). ers and resistance of the respiratory system (rrs) were obtained by fitting flow and pao signals breath by breath to the first order equation. ecw and resistance of the chest wall (rcw) were similarly obtained by fitting flow and pes signals breath by breath to the first order equation pertaining to the chest wall. el and lung resistance (rl) were obtained by subtracting ers and rrs from ecw and rcw, respectively. our ethical committee approved the protocol. data are shown as median (first and third quartiles). comparisons between positions were made by using paired-t-test. results twenty-nine patients, males, of ( - ) years, saps ( - ) and sofa score ( - ) were included ( - ) days after ards criteria were met. the ards severity was moderate in cases ( %) and severe in ( %). tidal volume averaged . ( . - ) ml/kg predicted body weight, peep ( - ) cmh o, fio ( - ) %, pao /fio ( - ) mmhg. the cause of ards was pulmonary in cases ( %), extra pulmonary in ( %) and undetermined in ( %). lateral positioning was on the right side in ( . %) and on the left side in patients ( . %). the results are shown in the table . conclusion during prone positioning in ards patients, as compared to sp we observed a higher rl in lp and an increased ecw in pp. introduction neuromuscular blocking agents (nmba) could exert beneficial effects in acute respiratory distress syndrome (ards) through properties on respiratory mechanics and particularly in modifying transpulmonary pressures (pl). patients and methods prospective randomized control study in moderate to severe ards patients within the first h of the onset of ards. all patients were monitored by an esophageal catheter and followed during h. moderate ards patients were randomized in two groups according to the systematic administration of a h continuous infusion of cisatracurium besylate or not (control group). the severe ards patients group received a h continuous infusion of cisatracurium besylate. the evolution during the h of the study of the oxygenation and the respiratory mechanics including inspiratory and expiratory transpulmonary pressures and driving pressure were assessed and compared. delta transpulmonary pressure (∆pl) was defined as inspiratory pl minus expiratory pl. results thirty patients were included, in the moderate ards group and in the severe ards group. nmba infusion was associated with an improvement in oxygenation both the moderate and the severe ards patients group accompanied by a decrease in both the plateau pressure and the total positive end expiratory pressure. the mean inspiratory and expiratory pl were higher in the moderate ards patients group receiving nmba as compared with the control group (fig. ) . in contrast, there was no modification of both the driving pressure and the ∆pl related to nmba administration. conclusion nmba could exert beneficial effects in moderate ards patients through higher observed inspiratory and expiratory transpulmonary pressures. none. introduction prone position (pp) is a major treatment in management of acute respiratory distress syndrome (ards). the use of pp in patients with severe ards associated with brain injury is at high risk of intracranial hypertension. the aim of this study is to analyze the effect of pp on intracranial pressure (icp) and cerebral perfusion pressure (cpp) in patients with ards and acute neurological condition requiring monitoring of icp. patients and methods it is a retrospective descriptive study including sixteen patients with acute brain injury (subarachnoid hemorrhage, severe head trauma, and hemorrhagic stroke) and continuous monitoring of icp who developed a severe ards during icu stay from january to december and for which pp was performed. pp sessions were analyzed. hemodynamic and respiratory parameters, blood oxygenation, pic and ppc were studied in supine, before pp and after pp. the study was approved by fics ethic comity. results a significant increase in pao /fio ratio was observed in pp, from ± to ± (p < . ). in pp, the icp was increased ± . - ± . mmhg (p < . ) while the cpp was stable ± versus ± mmhg (ns). median duration of pp session was h ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . increasing of icp during pp required medical treatment in sessions ( %). pp session was interrupted in sessions ( %). in subgroup of patients who respond to pp in terms of oxygenation, the increase of icp was lower than in non-responders ( vs %) (p < . ). cpp was not modified whatever the nature of the response to pp ( ± - ± in non-responders and from ± to ± in responders (ns)) (fig. ). discussion our study shows an improvement of oxygenation during pp in severe ards patient with acute brain injury. we observe a constant increment of pic during pp sessions. the increment of icp is less in responders to pp. significant increased icp requiring an enhancement in the medical treatment was observed in % of the cases, and lead in most cases to a discontinuation of the session. our data underlined the absolute necessity to monitor icp during pp session in patients with acute brain injury and ards, even if icp is controlled previously in supine. only prospective ( , ) and one retrospective studies evaluate the effects of pp on icp in patients with acute brain injury and acute respiratory failure (arf). they results are similar to ours. in all these studies, the severity of arf was often not well specified. roth and al. ( ) had included only % of ards in a population of patient with icp not controlled. in others studies, monitoring of icp during pp was not systematic. despite the retrospective nature of the study and the small number of patients, it is the only work studying the effects of pp on intracranial pressure in patients with acute brain injury at risk for intracranial hypertension and severe ards according to the berlin's definition. conclusion our work suggest that pp is a quite secure technique for use for the treatment of severe ards even patients at risk of intracranial hypertension with a benefit in terms of oxygenation without major increase of icp particularly in pp responders. introduction influenza-associated acute respiratory distress syndrome (ards) requiring extracorporeal membrane oxygenation (ecmo) support is known to have a good prognosis ( ). however, the incidence and impact of co-infection in this setting remain unknown. we conducted a retrospective, observational analysis of data prospectively collected from all patients admitted to our medical icu who received ecmo support for influenza-associated ards between and . co-infection was defined as isolation of a pathogen in the lower respiratory tract at a significant level or in the blood during the h following hospital admission. when no pathogen was identified in a patient receiving antibiotics prior to bacteriological sampling, an independent adjudication committee reviewed all charts to assess if the patient had a "high probability" or "low probability" for bacterial co-infection, based on clinical, radiological and biological results available. results are presented as median [iqr] . results among the patients hospitalized for an influenzaassociated infection in our icu, had an ards requiring support by either veno-venous-(vv, n = ), venoarterial (va, n = ) or venoarterio-venous-(vav; n = ) ecmo. - . ), pre-ecmo sofa score > (or . ; % ci . - . ) as independent predictors of hospital mortality, but not co-infection (or . , % ci . - . ). in a second analysis, patients with proven co-infection and high probability of co-infection were grouped and compared to patients with no co-infection and low probability of co-infection; and results were similar. as compared to others co-infected patients, those co-infected with a pvl-positive s. aureus had same characteristics and similar mortality rate, but all received a treatment active against pvl production. conclusion co-infection is frequent in patients with influenzaassociated ards supported by ecmo, occurring in roughly % of the cases. mortality of patients with co-infection is higher than those without, but seems mainly due to the severity of the disease. s. aureus was the most frequently identified pathogen, with a high prevalence of pvl-positive s. aureus, infection with a pvl-positive strain was not associated with a poorer outcome as compared to other co-infections. whether a treatment active against pvl production should be given in those patients remains to be determined. none. the pancreaticoduodenectomy (pd) is major surgery in visceral surgery. this technique performed for the first time in by whipple has seen much progress and development over the years that have enabled a significant reduction in mortality, while the morbidity remains high. the aim of this study was to analyze postoperative morbidity pancreaticoduodenectomies. we retrospectively studied cases of cephalic duodenopancreatectomy at the department of surgical emergencies resuscitation (wing ) spanning years, between january and december . the average age of patients was . years with % of females and % of males, the frequence of pancreatic resections was years. the indications of cephalic duodenopancreatectomy were: tumors of pancreatic head ( %), ampulla vater ( %), duodenum tumors ( %). the restoration of continuity after cephalic duodenopancreatectomy was realized with a rate of % for pancreaticogastrostomy and % for pancreaticojejunostomy. the average hospital stay was , days, with extreme lengths of - days. the postoperative course was marked by the occurrence of deaths ( %), the morbidity rate was , % after pj and % after pg; the most frequent complications were the pancreatic fistula ( %), the postoperative peritonitis ( %), the digestive bleeding ( %), the gastroparesis ( %). conclusion advances in the overall care of patients by surgical teams, anesthesiologists and intensivists, the dpc mortality is currently low in experienced centers. the multidisciplinary, involving surgeons, radiologists and especially intensive care, to manage more effectively the complications of this surgery remains burdened with high morbidity. introduction severe acute pancreatitis (sap) is a common but potentially lethal pathology due to the multiplicity and severity of complications that can occur at all stages of evolution. in the last decade, mini-invasive interventional treatments of infected pancreatic necrosis (ipn) have been developed. the aim of the present study was to assess the management and outcomes of sap patients, as well as to identify the role of ipn. this was a retrospective study of prospectively collected data from all consecutive patients admitted in intensive care unit (icu) in a single french center (hospital of nantes) from to . using logistic regression, we evaluated the association between ipn and patients characteristics at baseline and the outcomes. (fig. ) , highlighting the prognostic importance of respiratory failure and acute renal failure at the time of lt, as well as complex interactions between donor and recipient features. conclusion ventilator support and/or acute renal failure at the time of lt are major predictors of mortality but complex recipients/donors relationships may moderate these associations, as demonstrated by our cart analysis. none. subtotal gastrectomy ( / ). enlarged gastrectomy was performed in patients ( %). the mean operative time was . ± min. per-operative transfusion was required in patients ( . %). the average length of stay in icu was . ± days. postoperative mortality was . %. in our series, patients ( . %) had at least one postoperative complication: an anastomotic fistula diagnosed in patients ( . %), patients ( . %) had postoperative peritonitis and patients had ventilator associated pneumonia. reoperation was necessary for patients ( . %), it was performed after . days ( - days). in univariate analysis, risk factors for postoperative morbidity after gastrectomy was hypoalbuminemia (p = . ), anemia (p = . ), bmi (p = . ) and malnutrition (p = . ). age, sex, neoadjuvant chemotherapy, extended lymphadenectomy, splenectomy or pancreatosplenectomy, total gastrectomy and operative time were not significantly associated with higher postoperative morbidity. in multivariate analysis, malnutrition (p = . ) and bmi (p = . ) were significantly associated with the occurrence of postoperative complications. conclusion the results of our study are similar to those reported in medical literature. preoperative evaluation and nutritional rehabilitation are crucial to improve patient's outcome and reduce morbidity and mortality after gastrectomy for cancer. the mesenteric ischemia is a condition relatively rarely. it is marked by high mortality. mortality is primarily related to the land on which ischemia occurs and especially the time taken to diagnose. this delay is due to the low specificity of clinical signs and the absence of diagnostic laboratory test. the mesenteric ischemia remains a diagnostic and therapeutic challenge. patients and methods twenty cases of acute mesenteric ischemia have been collected at the surgical resuscitation (resuscitation ) at the hospital center ibn rochd of casablanca from january to december . results the mean age of our patients is year old. it is about a disease that the incidence increases these last years, particularly because of the waxing number of old patients and/or suffers from advanced cardiovascular diseases. the cardiovascular risk factor has been present in % of our patients. the abdominal pain has been present in all the patients. it is a sudden, intensive pain localized the most often at the level of the epigastria, becomes diffuse in few hours or even few days. other clinical signs have been described as the bilious vomiting that becomes fecaloid after few days. the digestive hemorrhages as the moelena and the hematemeses. a stop of the matter and the gazes was noticed in % of our patients. the absence of specificity of the clinical signs forced the realization of complementary examinations. the scanner becomes the reference imaging. it permits a differential diagnosis, the search of direct signs of vascular obstruction and the emphasis of intestinal pain. four etiologies are noticed: the arterial occlusion by emboli ( %), the arterial thrombosis ( %), the venous thrombosis ( %) and the "non occlusive" form ( %). the strategy of management of the acute mesenteric ischemia is multidisciplinary, based on the equips of radiology, vascular surgery and/ or visceral surgery and resuscitation. the treatment consists in measures of general resuscitation, the techniques of endoluminal vascular disobstruction and techniques of surgical revascularization. in spite of the improvements in the diagnosis and the therapeutic procedure of the ima, the disease still know a rate of mortality between and % according the studies. in our study, we noticed cases of death ( %), cases of good recovery ( %), cases are unknown evolution ( %). conclusion it is a vital emergency that the evolution still knows great mortality. it is very important to remind the acute mesenteric ischemia in the case of any acute abdominal symptom in order to anticipate about the natural evolution and to act in a reversible stage of the ischemia. none. introduction emergency departments staff are frequently exposed to many complex stressful situations and consequently burnout syndrome. our study aimed to describe epidemiological particularities and determine the risk factors of burnout syndrome in different categories of emergency. patients and methods we studied five academics and four regional hospitals. the level of burnout was assessed using the "maslach burn out inventory" score and the degree of depression with major depression inventory (mdi) test. results one hundred and forty-three correctly completed questionnaires were collected. the mean age of study population was ± years. sex-ratio was at . . fifty-one per cent of the care staff were married. physicians represented % and paramedical %. the general frequency of burnout syndrome was % (n = ). low level burnout was present in %, moderate level in % and high level in %. the depression frequency was %. a statistically significant correlation was found between burnout and depression firstly (p = . ) and between burnout and lack of equipment (p = . ). their relative risk was . [ . , ] and . [ . , . ] respectively). main risk factors associated with high level burnout are detailed in table . conclusion burnout syndrome frequency in our emergency departments is alarming. helping to resolve social and psychological problems and improving work conditions may help to decrease it. the healthcare activity is recognized as a major polluting activity. in france, it generates , tons of waste cremated each year, and represents % of the tertiary energy consumptions. in the united states, it generates tons of waste per day and % of total co emissions in were attributed to him. ultimately, such waste production is associated with adverse environmental and health effects. nevertheless, near half of the hospital waste would be recyclable, particularly in our intensive care units (icu) [ ] . furthermore, sustainable development solutions generate profits. the aim of this study is to make an overview of waste produced in a icu and offer solutions to conserve natural resources and reduce the carbon footprint bound to the healthcare activity. materials and methods experimental study, single-center, concerning a period of months in an icu-high surveillance unit compound of beds. we have identified all waste generated. our packaging were given to the recycling company in connection with the hospital. then we have studied the impact of the implementation of sustainable development solutions. results firstly, we have studied the non-recycled waste and the quantity produced over a period of month. approximately kg of waste is produced per patient per day with % of infectious waste and % of general waste. these results were linked with a bad distribution of garbage bags in the rooms ( l of infectious waste versus l of general waste). secondly, we have improved our way to sort and consume and we have created recycling dies without compromising patient safety. all these measures have not increased workload. changing bags in the rooms ( l of infectious waste and bags of l of general waste) allowed to reach the normal goals of sectors with a net benefit estimated at euros per year. the medical broken glass containing drugs was thrown into plastic containers of l for infectious waste to prevent the risk of cuts. by creating a specific die intended to the general waste, we could quantify the production of this glass to kg per week and to spare the use and the incineration of containers of l per year (global economy of euros). plastic packaging represented an important proportion of the cremated waste. we have created sectors of recycling including the polypropylene ( - kg per month), the polyethylene colorless and colored polyethylene. this plastic is sold to be recycled without additional cost for the hospital. the linerboards was cremated. we have created a recycling die ( kg per month). this sector was subsequently extended to the entire hospital structure, particularly the pharmacy that produces containers of l per month. they are now sold without additional cost. many unnecessary plastic waste is generated daily. we have removed using mild soap plastic bottles of ml by using the same mild soap in pump of ml (economy of euros). the use of l plastic bags for the transitional deposit of linen has been deleted (economy of euros). concerning the paper: % of the impressions were made in simplex. printers were parametrized on both sides by default allowing the economy of reams per year ( , sheets), several thousand liters of water and the reduction of co emissions. discussion recycling is only one component of the sustainable development in health. other avenues that could be considered to improve icu sustainability would include examining water use (for linen), electricity use (reducing non-essential use at night…). beyond these actions, we need to encourage our suppliers to turn to sustainable and recyclable packages to reduce the use of polluting and depletable fossil fuels such as oil. but also to develop with them circular economies where waste is returned to them to be reused. conclusion we must ask the question also resuscitate our tons of waste. our icu produce large quantities of waste (over tons per year per bed). however, a significant proportion, especially plastic, is recyclable with a significant environmental and financial benefit. waste management also requires an optimal and rational use of supplies because "the best waste is that which is not produced" and that excess is not a guarantee of quality. as already said st exupéry in : "we do not inherit the earth from our parents, we borrow it from our children. " so do not expect tomorrow to reduce major adverse ecological impact paradoxically generated by a great profession whose ultimate goal is to cure people. moreover, an external consultant is rarely applied and palliative cares are insufficiently developed after «non-readmission» decisions. for providing corrective measures, this study lead to propose a «nonreadmission» process by integrating the discussion for a real «patient's care project» at the end of the icu hospitalization. this process would lead to collect patient's opinion through advance directives, to ensure a collegial discussion including an external consultant and to allow reevaluation of global patient's clinical status and one or more organ failure(s). then, «non-readmission» decisions would be integrated in a therapeutic project which would promote the initiation of a palliative care program if necessary. the purpose of this process is well to respect patient's autonomy and dignity as required by french law and medical ethics. the proportion of elderly patients is steadily increasing. due to the growth of this part of the population who suffer from multiple pathologies, the need for hospitalization in intensive care increases. according to the simulations, the proportion of octogenarian patients in icu will increase reaching the third of icu patients. while chronological age is not a significant factor of poor prognosis in the icu ( ), many factors should be taken into account to evaluate the relevance of icu admission in the senior population and withholding such intensification should be consensually discussed between clinicians and obviously as often as possible with the patient himself ( ) . the aim of the study was to assess the role of stakeholders (ward physicians, intensivists, family doctor and patient himself ) in the decision of withholding icu admission for elderly patients in our internal medicine department. we made a prospective observational monocentric study, including all the elderly patients (defined as older than ) admitted in the internal medicine department from january to june . the only non-inclusion criterion was patient's refusal to participate to the survey. collected data involve physiological (cognitive, autonomy, nutritional status), morbidities (acute and chronic diseases) and social parameters (marital status, relatives). and evaluation of quality of life by the patient himself using an analog visual scale was also obtained. internal medicine physicians were asked to report any icu withholds decision for their patients. in absence of notification, every physician was questioned again the day of the concerned patient's discharge. results one hundred ninety-one patients were included between january and june . factors associated with a significant reduction of in hospital mortality were higher age (p = . ), higher lactate level (p = . ), chronic obstructive pulmonary disease (p = . ), diabetes mellitus (p = . ), immunodepression (p = . ) and respiratory failure (p = . ). conclusion in patients hospitalized for vs high body mass index, low left ventricular systolic function, high white blood cell count, low creatinine clearance, high lactate level and st-segment depression are the variables correlating significantly with high-sensitivity troponin-t concentrations. peak of hstnt was not significantly associated with in-hospital mortality in this setting. introduction mitochondria are evolutionary endosymbionts that are derived from ancestral aerobic bacteria and so might bear and release bacterial molecular motifs supporting the role of mitochondria in danger signal regulations. free circulating mitochondrial dna (mtdna) is elevated in a wild range of critical illness observed in intensive care units, and is associated with bad outcomes and mortality. the mtdna is a molecular pattern that belongs to mitochondrial damage associated molecular patterns (mtdamps), and can interact with pattern recognition receptors (prr) to induce self defense reaction. free mtdna activates inflammatory signaling pathways through toll-like endosomal receptor (tlr ) interactions. nevertheless, new evidence advocates a role of the receptor for advanced glycation end-products (rage) in mtdna signaling. experimental data suggest a role of mtdna-prr interaction in systemic inflammation and organ dysfunctions as septic acute kidney injury or pulmonary inflammation. impact of free circulating mtdna on endothelial cell is not known. the main purpose of this study was to test whether mtdamps and mtdna can induce endothelial dysfunction. we also evaluated the role of mtdna-rage axis in mtdamps induced endothelial dysfunction. mitochondria were isolated from livers of wild type c b mice. isolated mitochondria were sonicated on ice to obtain mtdamp preparations. semi quantitative evaluation of mtdamp content was tested by qpcr, with specific markers of mtdna (cytochrome b (cytb), nadph oxidase (nd )). intraperitoneal injection of mg of mtdamps was used as experimental model in wild type and rage ko mice, as previously described [ ] . the mtdamps were also administrated after ex vivo dnase preparation. endothelial function was assessed with a mulvany-halpern style myograph, h after mtdamp administrations on aorta (conductive vessel) and on d division of mesenteric artery (resistive vessel). endothelial-dependent relaxation was studied by cumulative expositions of the vessels to acetylcholine ( . - - . - m). endothelial-independent relaxation was studied by sodium nitroprussiate exposition. results the mtdamps preparation contains a high quantity of mtdna with a /cycle threshold (ct) ratio of . for cytb expression. intraperitoneal administrations of mtdamps induced a decrease of endothelial-dependent relaxation mainly on conductive vessel (p = . , n = per group) and to a lesser extent on resistive vessel (p = . , n = per group). rage-ko mice were protected from mtdamps-induced aorta dysfunction (p = . , n = per group). the ex vivo exposition of mtdamps to a dnase preparation decreased mtdna content in mtdamps solution with a /ct ratio of . for cytb expression. eventually, the pretreatment of mtdamps with a dnase preparation prevented the mtdamps-induced aorta dysfunction (p = . , n = ). discussion more than prognostic markers, mtdamps particularly mtdna seems implicated in endothelial dysfunction in critically ill patient. new evidence suggest rage interaction in endosomal tlr pro-inflammatory and pro-oxidant response to mtdna [ ] . also in sepsis, physiological clearance of circulating dna might be impaired, this results comfort the possibility of therapeutic regulation of free circulating mtdna to prevent septic organ dysfunction related to mtdamps accumulations. conclusion exogenous mtdamps can induce endothelial dysfunction in mice. the mtdna-rage axis is a key component of the signaling pathway involved in this dysfunction. the use of dynamic parameters to assess fluid responsiveness was supported by cyclic changes in stroke volume induced by mechanical ventilation. however, these parameters have several limits. venous to arterial carbon dioxide difference inversely related to cardiac index. consequently, fluid administration would be beneficial if carbon dioxide gap increases. objective to investigate whether carbon dioxide gap predicts fluid responsiveness in patients with acute circulatory failure. patients and methods we conducted a prospective study in the medical intensive care unit of hospital taher sfar at mahdia, between march and april . patients with circulatory failure and who required mechanical ventilation were included. we measured the variation of cardiac index between baseline and after volume expansion of ml of saline fluid. the picco was used to measure cardiac index. response to fluid challenge was defined as a % increase in cardiac index. before and after fluid administration, we recorded carbon dioxide difference and hemodynamic parameters. results among included patients, ( %) were responders. the causes of acute circulatory failure were septic shock (n = ), cardiogenic shock (n = ), and hypovolemia (n = ). carbone dioxide gap was significantly higher in responders group ( ± vs ± mmhg, p = . ). the area under the roc curve for carbon dioxide gap was . ( % ci . - . ). the best cutoff value was mmhg (sensibility = %, specificity = %, positive predictive value = % and negative predictive value = %). the area under the roc curve for delta carbon dioxide was . ( % ci . - . ). conclusion in this study, baseline carbon dioxide gap was not universal indicator to predict the fluid responsiveness in patient with circulatory failure. introduction supraventricular arrhythmia (sva) is commun in intensive care unit (icu). its incidence seems to be higher in patients with sepstic shock. sepsis-associated myocardial dysfunction promote the occurrence of sva by constituting an arrythmogenic substrate or under the effect of inotropic drugs. the aim of this study is to assess the incidence and prognostic impact of sva in patients with septic shock. patients and methods we retrospectively studied all patients with new onset sva suffering from septic shock in non cardiac surgical icu. myocardial dysfunction was evaluated by transthoracic echography (tte) after an adequate cardiac resuscitation using intravenous fluids expansion and adjunctive vasoactive agents. sva was detected by the electrocardiogram scope. during the study period clinical and biologic characteristics, hemodynamic tolerance (vasopressors doses, arterial pressure changes), current treatment (such as corticoid), duration of mechanical ventilation, duration of vasopressor requirement and hospital mortality were collected. results sixty patients were included in the study. the sva occurred in patients, with an incidence of %. the median time to onset was days. cardioversion was performed for patients with an effectiveness of %. clinical and biological characteristics were similar between the groups with and without sva: saps and sofa score at the beginning of septic shock, the existence of ards and cardiac biomarkers (nt-probnp, troponin). however, renal failure and the use of corticoid in septic shock were more frequent in the group with sva. the maximum doses of vasopressor agent were not significantly different between the groups with or without sva. myocardial dysfunction in sepsis defined by the left ventricle ejection fraction (lvef) less than % (or the need for inotropic drug for lvef > %) was not associated with the occurrence of sva (+sva group: n = ; −sva group: n = ; p: . ). sva was poorly-tolerated, observed by a significant decrease in mean arterial pressure and a significant increase in norepinephrine doses within h of the start of sva. the occurrence of sva was associated with longer duration of use of vasopressor agent and a longer duration stay in icu (+sva group: days, −sva group: days; p = . ). there was no difference in duration of mechanical ventilation and hospital mortality between the two groups. conclusion the occurrence of sva is common in septic shock, poorly tolerated hemodynamically and associated with longer duration stay in the icu and vasopressor need. sepsis myocardial dysfunction isn't necessarily associated to the occurrence of sva. introduction a short term beneficial effect of prone position on cardiac index has been shown in % of ards patients, and was related to an increase in cardiac preload in preload responsive patients ( ) . the aim of this study was to evaluate the long term hemodynamic response to prone position in a larger series of ards patients. patients and methods single center retrospective observational study performed on ards patients hospitalized in a medical icu between july and march . patients included were adults fulfilling the berlin definition for ards, undergoing at least one prone position session, under hemodynamic monitoring by the picco ® device, with availability of hemodynamic measurements performed before (t ), at the end (t ), and after the prone position session (t ). prone position sessions were excluded if they were performed > days after ards onset. the following variables were recorded: demographic, sapsii, ards severity and risk factor, sofa score and cumulative fluid balance at pp onset, delay between ards session and pp session, hemodynamic, arterial blood gas, ventilatory settings, plateau pressure, catecholamine dose and additional treatments. statistical analyses were performed using prone position session as statistical unit and mixed models taking into account both multiple prone position sessions by patient and multiple measurements during a prone position session. p < . was chosen for statistical significance. data are expressed as mean ± standard deviation. results patients fulfilled the inclusion criteria over the study period, totalizing prone position sessions ( ± sessions per patient). patients' age was ± y, % were male, % fulfilled the criteria for severe ards, and sapsii at icu admission was ± . ards risk factors were pneumonia in ( %), aspiration pneumonia in ( %), and sepsis in ( %) patients. duration of prone position sessions was ± h. hemodynamic measurements were performed in pp ± h after pp session onset. at session onset, sofa score was ± , and cumulated fluid balance was . ± . l. vasopressor were used in %, inhaled nitric oxide in %, and neuromuscular blocking agents in % of the sessions. hemodynamic and respiratory parameters before, during and after the prone position sessions are reported in table . cardiac index increased by at least %, decreased by at least % or remained stable in ( %), ( %), and ( %) of the sessions, respectively. as compared to both other groups, pp sessions with significant increase in cardiac index had the following significant differences at t by univariate analysis: lower cardiac index, lower global end-diastolic volume, lower cardiac function index, and lower vasopressor dose. multivariate analysis is under investigation. conclusion prone position is associated with an increase in global end-diastolic volume, reversible after return in supine position that may explain the positive effect of pp on cardiac index observed in ¼ of the pp sessions. introduction make sure that our patient have a good circulatory condition is a daily challenge for the intensivist. one of the therapeutics is fluid and one of his purpose is to increase venous return and then cardiac output. in order to examine that, there are several tools as the transthoracic echocardiogram wich allows the visualisation and the study of the respiratory variability from the inferior vena cava (ivc). unfortunately there are some situations where the ivc visualisation is difficult (obesity, gut surgery, emphysema). the ivc is easily seen by a transhepatic ultrasound in her retrohepatic section. we make the hypothesis that the shape of the ivc could be predictive of fluid responsiveness. we have performed fluid challenge in patients under mechanical ventilation. the need for fluid therapy is the intensivist in charge decision. we performed a echocardiogram and we take two measures of the icv: major axis and minor axis, the icv is measured avec the sus hepatic vena. a elastometry index (ei) is determined which is the ratio of minor axis to minor axis. the fluid challenge is ml of isotonic saline then we perform a new echocardiogram. a tag is written on the patient to take the same ultrasound slice. we retain one increase of % of the cardiac index (ic) as a success of the filling. we exclude the presenting patients a right cardiac insufficiency, an arrhythmia and/or a htap. the statistical analysis is realized with the software r. results between august, and january, we included patients. the average age is of years ( - ), igs of ( - ), ejectionnal fraction of % - ) and the s wave tricuspid is ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the causes of the filling were an oliguria ( %), a low blood pressure ( %), a low cardiac output ( %), a hyperlactatémia ( %) and an other cause in % of the cases. we find a positive correlation between the ei and the increase of the ic, also for the area of the vci and the respiratory variations of the vci (p . ) the other variables are not predictive (bp, e/e' , e/a). the data are summarized in the picture . roc curves has been established ( only % of the journals studied required authors to use stard. a high impact factor and the year of the study were the items associated with a better sqs the presence of a conflict of interest was associated with a lower sqs in univariate analysis. a higher impact factor (> ), was the only independent factors statistically significantly (p = . ) associated with higher sqs in a multivariate regression model. discussion our study showed that the sqs were very low. assessment of a study depends on quality of reporting. blindness and participant sampling are the cornerstone to evaluate such bias as spectrum, verification, review and selection bias of a study, and were unfortunately scarcely reported compared to existing data in diagnosis accuracy reporting. one of the limitation is the years sample of the study. we have planned to continue the analysis for a -year review starting just after the stard publication. conclusion our study showed that several items remain poorly reported. we recommend systematic use of stard criteria in the elaboration and reporting of future studies that evaluates the preload dependence. introduction neurological impairment, i.e. encephalopathy, is commonly observed in patients with decompensated cirrhosis and/or portosystemic shunts admitted in icu. often ascribed to high plasmatic levels of ammonia, encephalopathy could also be induced by drugs or infection, due to altered blood-brain barrier (bbb) permeability. this latter setting is often underdiagnosed and encephalopathy related to hyperammonemia (so called hepatic encephalopathy-he) being pointed out as the culpit of all neurological symptoms in cirrhotic patients. quinolones and betalactamins were recently found in the cerebrospinal fluid of he patients and it has been shown that the expression of efflux pumps, responsible for drugs passing through the bbb, was altered in animal models of he. the purpose of this study was to assess the incidence of neurological impairment, i.e. encephalopathy, in cirrhotic patients hospitalized in discussion overall, we reported a higher rate of lumbar puncture than those reporting in others studies concerning status epilepticus. furthermore the rate of % of pleocytosis directly linked to status epilepticus is slightly higher than in most studies. unfortunately we didn't realize a second lumbar puncture to assess the pleocytosis normalization during the days following the first lumbar puncture. the pathophysiological hypothesis of this phenomenon may be that prolonged/repeated seizures during status epilepticus would induce a blood-brain barrier dysfunction thereby favoring a cerebrospinal pleocytosis. conclusion in our study, % of status epilepticus without infectious or neoplastic origin had a cerebrospinal pleocytosis directly linked to status epilepticus. this pleocytosis was significantly associated with myoclonic seizures and blood leukocytosis. these data may help to interpretation of cerebrospinal fluid pleocytosis during status epilepticus. introduction neurological prognostication from cardiac arrest survivor is a current concern. eeg patterns and nse dosage are two important prognostic factors. nse threshold for prediction of poor outcome appear controversial, in part, because of variability in dosage timing and measurement techniques. synek score is routinely used in our center to classify comatose patients in post cardiac arrest. the aim of this study was to assess the prognostic value of nse and synek classification to predict poor neurological outcome. introduction traumatic brain injury (tbi) is a major public health problem. it is the leading cause of death and disability in young subjects. one of the principles of the tbi management is prevention of secondary cerebral insults including maintaining perfusion and cerebral oxygenation, control of intracranial pressure (icp). an increase in icp above mmhg is associated with poor outcome. cerebral hypoxia can occur with normal level of icp and cerebral perfusion pressure (cpp).monitoring of regional partial pressure of brain tissue oxygen (pbto ) is a safe and reliable method for measuring cerebral oxygenation. a retrospective single-center observational study was conducted between january and december , aimed to study the influence of pbto with severe tbi patients outcome at months through glasgow outcome scale (gos). the hourly values of icp, pbto and cpp were recovered on daily monitoring sheets. we compared two groups according to their gos. during the study period, patients underwent a monitoring icp and pbto . results the mean age was . ± . years. . % were men. the initial glasgow score was . ± . . the mean simplified acute physiology score (saps ii) was . ± . and injury severity score (iss) . ± . . at months, patients had died (gos ). forty patients had a good outcome: gos - (group ). sixteen patients had poor outcome: gos - (group ). in group , there are significantly more pbto hourly values below mmhg at day ( . ± . vs . ± , in group , p = . ); and more pbto hourly values greater than mmhg at day ( . ± . vs . ± . , p = . ). conclusion pbto less than mmhg or greater than mmhg at day is associated with poor outcome at months in the severe tbi. the pbto allows a more individual approach of monitored tbi. none. introduction organ donation in patients after a decision to withdraw life-supportive therapies (wlst) (maastricht condition: m ) have been performed in our hospital since may . we report here main characteristics of donors, data on m procedure and results on renal transplant recipients. patients and methods all potential donors were included in a survey from may to june , according to the french national m protocol defined by the french organ procurement agency (agence de la biomédecine:abm) [ ] .the demographical, clinical and biological characteristics of the donors, the different deadlines and times of the protocol and data of renal transplantation were collected and analyzed. results patients had inclusion criteria. patients were admitted in intensive care unit for cardiac arrest ( %), strokes ( %), traumatic brain injury ( %), ards ( %). of them, procedures ( %) were stopped ( refusals of organ donation, medical contra-indications discovered with additional exams, failure of vessel cannulation, deaths more than h after extubation). kidneys were harvested and transplantations performed ( renal cancer discovered during procurement surgery).the characteristics of the donors, deadlines of the protocol and transplant recipients are reported in the table . conclusion the french programm maastricht offered a new possibility of organ donation in our hospital. thanks to these donors, the number of renal grafts increases and the preliminary results on transplant recipients are encouraging in line with the preliminary report of the abm. nevertheless, it is necessary to follow the transplant recipients and extend the procedure to new centres. in this study, we found some relevant risk factors for microaspiration (age, low score at gcs) consistent with literature on the subject. patients with paralytic agents had less gam which may be due to higher peep, higher cuff pressure and less enteral nutrition because of the severity of the underlying diseases. conclusion this study did not show any increased risk of microaspiration in intubated copd patients, whatever stage of copd. introduction protected specimen brush (psb) is considered to be one of the standard methods for the diagnosis of ventilator-associated pneumonia (vap). to our knowledge, there is no study assessing effect of prior antibiotherapy on direct examination, bacteriological culture and concordance of direct microscopy and culture. patients and methods all consecutive episodes of suspected vap were retrospectively evaluated between january and december in a -bed intensive care unit. patient's characteristics and preexisting conditions were abstracted from the medical charts. after assessment of vap probability using the clinical pulmonary infection score (cpis), psb were performed in patients with a cpis of or more. based on antibiotic treatment in patients when bacteriological specimens were obtained, two groups were defined: no antibiotic group and antibiotic treatment started before psb group. two independent bacteriologists retrospectively reviewed direct examination and culture of psb to assess bacteriological concordance, defined as non-concordant when direct examination and culture were different, concordant when direct examination and culture were similar and partially concordant when either direct examination or culture were comparable but with other microorganisms lacking in one or the other method. results during this -months period, among mechanically ventilated patients, episodes of suspected vap with psb were evaluated. we found % of psb (n = ) performed without antibiotic treatment and % of psb (n = ) performed under antibiotherapy. we found no significant differences in patient's demographics, characteristics, and severity between both groups. patients received antibiotics for the following reasons: aspiration pneumonia (n = ), peritonitis (n = ), vap (n = ), community-acquired pneumonia (n = ), septic shock of unknown origin (n = ), pyelonephritis (n = ), meningitis (n = ), acute pancreatitis (n = ) and others (n = ). the median duration of mechanical ventilation in the antibiotic receiving group and in the group without antibiotics was . days (iqr; - days) and days (iqr: - ), respectively. when psb was performed under antibiotic treatment, direct examination was positive in % (n = ), culture was positive in % (n = ) and those methods were concordant, non concordant and partially concordant in % (n = ), % (n = ) and % (n = ), respectively. on the other hand, when psb was performed without antibiotics, direct examination was positive in % (n = ), culture was positive in % (n = ) and those methods were concordant, non concordant and partially concordant in % (n = ), % (n = ) and % (n = ), respectively. in univariate analysis, we found a significantly higher proportion of negative direct examination and negative culture in the antibiotic group (p > . ). moreover, these methods were significantly more frequently concordant (p = . ), with a higher rate of both negative microscopic exam and culture when compared to the no antibiotic group ( %, n = vs %, n = ). surprisingly, among the patients previously treated with antibiotics with positive culture, % (n = ) of the microorganisms showed antibiotics sensitivity. discussion whether prior antibiotic treatment may induce false negative of false positive treatment is a well-recognized phenomenon, the precise effect of antibiotics on direct examination and quantitative culture is not well assessed in vap. moreover, despite recent development of clinico-radiological score, diagnosis of vap remains difficult, with no gold-standard. therefore, bacteriological guided therapy is of particular importance. we found psb realization under antibiotic treatment is associated with a lower rate of positive direct examination and culture and suggest performing these bacteriological samples without antibiotherapy. some authors have suggested lowering the diagnostic threshold point of this bacteriological technique in order to preserve its accuracy. however, we can postulate that microorganisms responsible of superinfection in mechanically ventilated patients treated with antibiotics may be resistant and therefore the psb could be positive. conclusion in patients with a high pre-test probability of ventilatoracquired pneumonia, recent introduction of antibiotics significantly reduced the diagnostic accuracy of protected brush specimen by reducing rates of positive direct examination and culture. further studies should evaluate if antibiotic discontinuation may revert this effect. ann. intensive care , (suppl ): we have had non conflict of interest in this study. results we included patients in the phase and patients in the phase . baseline characteristics of patients were similar in both groups. compliance with all the measures has been improved between the two period from to . %. the incidence density decreased from . to . vap per ventilator days between observational and interventional period, but the all-cause mortality was almost equal in the groups ( . vs. %). discussion with the implementation of our bundle, observance of the team were improved in the second group, compared to the first and the incidence density decreased from . to . vap per ventilator days between both period. this result is consistent with the littérature. sure enough, many studies show the same effect of vap prevention with a decrease of nearly % of the incidence density of vap, after implementation of a «ventilator -bundle [ ] . conclusion the implementation of a "ventilator bundle, " has significantly reduced the incidence of vap in our service. in the contrary, our study failed to demonstrate a reduction in mortality. introduction with an increasing incidence and high mortality rates, sepsis is a public health issue. there is growing evidence that sepsis induces long lasting alterations of transcriptional programs through epigenetic mechanisms that may lead to protracted inflammation, organ failure, sepsis-induced immune suppression (siis), secondary infections and death. we hypothesized that epigenetic changes contribute to the pathophysiology of siis. to test this hypothesis, we studied the effects of histone deacetylases (hdac) inhibition with trichostatin a (tsa) in a double-hit murine model of siis and secondary pneumonia. materials and methods c bl/ mice were treated with tsa ( mg/ kg ip) or saline serum (ctl) min before induction of sepsis by cecal ligation and puncture (clp). surviving mice underwent intratracheal instillation of . × cfu of pseudomonas aeruginosa days after clp. we evaluated the effect of tsa on survival and cellular responses to the primary and secondary infections. cellular responses in the blood, spleen and bal were assessed by flow cytometry after clp (days , & ) and after pneumonia ( & h). we also studied lymphocyte apoptosis and dendritic cells (dc) expression of cd , cd , and mhcii. bacterial clearance was assessed in the bal and in the blood and h after pneumonia. continuous variables represented as mean ± sd were compared using student t test. kaplan-meier curves were compared by the log rank test. p < . indicated statistically significant differences. results whereas treatment with tsa did not change survival after clp, tsa improved survival after tracheal instillation of p. aeruginosa (p = . , fig. ). tsa-treated mice had significantly higher absolute dc, t and b-lymphocytes counts with reduced lymphocyte apoptosis after clp. four hours after secondary pneumonia, tsa-treated mice had significantly higher dc counts and improved bacterial clearance in the bal, with reduced systemic dissemination of p. aeruginosa. conclusion hdac inhibition with tsa improves survival in our murine model of secondary pneumonia, improves bacterial clearance and attenuate cellular features of siis. these results suggest that sepsisinduced epigenetic changes contribute to the advent of siis. comprehensive characterization of epigenetic changes associated with siis might allow us to identify new therapeutic targets to reprogram immune cells in sepsis and avoid siis. length of icu stay was ± days. patients acquired nis ( . % bsi, . % pneumonia, . % cri and . % uti. there was no bacteriological documentation of ni in . % of cases. nis occured days post burns. the most three isolated pathogens were: acinetobacter spp. ( %), p. aeruginosa ( . %) and extended spectrum betalactamase-producing enterobacteriaceae ( %). the most frequently administered antibiotics were polymyxin/carbapenem/teicoplanin combination ( %), polymyxin/carbapenem combination ( %) and carbapenem/tigecycline combination ( %). in our study, mortality rate was %. conclusion nosocomial infection occured in . % of cases in burn patients, caused by acinetobacter spp, p. aeruginosa and enterobacteriaceae blse. so, eradication of infection in burn patients require effective surveillance and infection control in order to reduce mortality rates, length of hospitalization and associated costs. introduction infection of the lower respiratory tract is the most common cause of infection in intensive care unit (icu) ( ) . although the attributable mortality of ventilator associated pneumonia remains debated, the recurrence of these infections is always associated with a significant morbidity ( ) . staphylococcus aureus methicillin-sensitive (sams) is one of the most frequently germs involved in icu pneumonia especially in trauma patients. the aim of the study was to establish the risk factors associated with microbiological treatment failure of pneumonia, caused by sams. materials and methods we retrospectively identified patients who developed a first episode of ventilator associated pneumonia caused by sams during a years-period ( - ). the primary end point was the microbiological treatment failure defined as a second episode of pneumonia caused by sams corresponding to either a persistent or a recurrence of the pneumonia (fig. ) . the primary aim of the study was to identify factors associated with a treatment failure, the secondary objective was to identify factors associated with the occurrence of second episode (i.e. persistent, recurrence, superinfection and/or relapse of pneumonia caused by any bacteria) during or after treatment of the first episode caused by sams. definition of outcomes was based after analysis of current concepts available in the literature. factors associated with primary and secondary objectives in univariate analysis (p-value < . ), or clinically relevant ones, were entered in a multivariate logistic regression. the final selection was performed using the stepwise selection based on the akaike criterion. results fifty-nine patients ( . %) developed a second episode of pneumonia and among them, ( . %) were considered as a microbiological failure. in a multivariate analysis, the association of oropharyngeal flora (fop) with the sams (or, . ; % ci, . - . ; p = . ) and the need of emergency surgery (or, . ; % ci, . - . ; p = . ) were predictive of a microbiological failure. empirical antibiotic therapy with amoxicillin-clavulanic acid (or, . ; % ci, . - . ; p = . ) and performing emergency surgery (or, . ; % ci, . - . ; p = . ) were predictors of a second episode of pneumonia caused by any bacteria. conclusion in this retrospective, monocentric study, the co presence of orophryngeal flora and the need of emergency surgery were associated with microbiological failure of pneumonia caused by sams in icu. introduction ventilator-associated pneumonia is a major iatrogenic problem since it is a cause of hospital morbidity, mortality and increase of health care costs. it has been studied many times, but data's revision is always necessary. our study aimed to describe epidemiology of ventilator-associated pneumonia and identify local causative pathogens. we carried out a prospective study in an intensive care unit. were included patients intubated for more than h, from april to may , and presenting signs of ventilator-associated pneumonia (fever, abundant and purulent secretion, increase of fio greater than . , signs on chest-x ray) with positive culture of endotracheal aspirate. were excluded patients with germ colonization. results a total of patients were ventilated for more than h. among them thirty-four patients aged of ± . years presented episodes of ventilator-associated pneumonia (that is . ± . episodes per patient). the mean sofa score was . ± . . the main reasons of mechanical ventilation were loss of consciousness secondary to poisoning ( %), respiratory distress ( %) and status epilepticus ( %). the mean duration of stay was . days with extremes at and days. the average time between hospitalization and suspicion of ventilator-associated pneumonia was . ± . days. the average value of the clinical pulmonary infection score at suspicion was ± . . the average time between recurrences was . days with extremes at and days. the culture of endotracheal aspirate identified two pathogens in %. it reveled acinetobacter baumanii in % in which % were imipenem resistant, pseudomonas aeroginosa in %, klebsielle pneumoniae in %, staphylococcus fig. see text for description aureus methicillin resistant in %. extended spectrum β-lactamases bacteria were found in % and carbapenemases producers in %. empirical antibiotherapy was always association of imipenem and colistin. it was necessary to adapt it to antibiograms in / . ventilator-associated pneumonia was complicated by septic shock in % and acute respiratory distress syndrome in %. patients evolved to healing in % of episodes (n = ), to superinfection in % (n = ) and to death in % (n = ). pseudomonas aeruginosa was the most frequent germ in superinfection ( / ) , acinétobacter baumanii was the most pathogen associated to death ( / ). conclusion ventilator-associated pneumonia is an iatrogenic disease that threatens lives. it's in part avoidable. preventive measures have to be implemented to reduce its frequency, consequences and costs. introduction during mechanical ventilation, mismatch between respiratory muscles activity and the assistance delivered by the ventilator results in dyspnea and asynchrony and is commonly observed in intensive care unit (icu) patients. proportional assisted ventilation (pav) is a ventilatory mode that adjusts the level of ventilator assistance to the activity of respiratory muscles estimated by an algorithm. to date, pav has been mostly studied in patients without severe dyspnea or asynchrony. we hypothesized that, compared to pressure support ventilation (psv), pav will prevent severe dyspnea or asynchrony. patients and methods were included icu mechanically ventilated patient exhibiting severe dyspnea or asynchrony with psv. three conditions were successively studied: ) psv on inclusion (baseline), ) psv after optimisation of ventilator settings in order to minimize dyspnoea and asynchrony (optimisation), and ) pav. ten-minutes recording were performed with each condition. the intensity of dyspnea was assessed by the visual analogic state (vas, only in patients able to communicate) and by the intensive care respiratory distress operating scale (ic-rdos) for all the patients. the electrical activity (emg) of extradiaphragmatic inspiratory muscles was measured. the fig. bayesian nma with random effect prevalence of asynchrony was quantified by the visual inspection of the airway flow and pressure traces. results patients were included, % male, aged [ - ] years, saps [ - ], mechanically ventilated for [ ] [ ] [ ] [ ] [ ] [ ] days. the tidal volume (tv) was higher in the optimisation and pav than in the basal condition (table ). the respiratory rate(rr) was lower with pav than in the other conditions. the dyspnea-vas was lower with optimisation and pav than with the basal conditions. the ic-rdos was lower with pav than with the two other conditions. the asynchrony index was lower with pav than with the two other conditions. parasternal emg activity was lower with pav and optimisation (fig. ) . conclusion in icu patients receiving mechanical ventilation with psv and exhibiting severe dyspnea or asynchrony, the optimisation of ventilator settings with psv and the pav mode decrease in the simiar way the severity of dyspnea and the prevalence of patient-ventilator asynchrony. introduction in spite of recent research and progress in weaning protocols, extubation failure still occurs in - % of patients and is associated with poor outcomes, with a mortality rate of - %. many risk factors for planned extubation failure have been suggested, including hypercapnia at end of spontaneous breathing trial (sbt). however, performing arterial blood gases at the end of sbt is not routinely recommended whereas etco may be routinely monitored during a low pressure support sbt. the aim of this prospective observational study was to determine the clinical usefulness of etco to predict extubation failure. patients and methods we recorded clinical data and etco during a successful h low level pressure support sbt (at the beginning, after min and at the end of the trial). patients ventilated through tracheostomy and unplanned extubations were excluded. extubation failure was defined as death or the need for reintubation within h ( ) after extubation; this delay was prolonged to days ( ) in case of noninvasive ventilation after extubation, which was systematic in older patients or those with cardiorespiratory disease, as per our weaning protocol. multivariable logistic regression analysis was performed to identify independent variables associated with extubation failure. results one hundred and fifteen ventilated patients were enrolled in our study from july to june . the median age of these patients was [ - ] years, their median simplified acute physiology score (saps) ii was [ - ] points and . % (n = ) were female. seventeen ( %) patients had chronic obstructive pulmonary disease. reintubation rate was % (n = ). etco at other time points as well as its changes during the sbt were also similar between groups. the three variables predicting extubation failure in the multivariable logistic regression model were a past medical history of cirrhosis, acute respiratory distress syndrome before weaning and lower minute ventilation at the end of sbt. conclusion etco during a successful sbt seems useless to predict outcome of extubation. introduction airway management in intensive care unit (icu) patients is challenging [ ] . "airway failure", defined as the inability to breathe without endotracheal tube, differs from "weaning failure", defined as the inability to breathe without an invasive mechanical ventilation. however, most of the studies assessing predictive factors of extubation failure did not separate airway from weaning failure. we aimed to describe incidence of extubation failure in critically ill patients, separating for the first time airway from weaning failure, in a prospective multicenter observational study. patients and methods a prospective, observational, multicenter study was conducted in french icus. all adult patients consecutively extubated in icu were included. an ethics committee approved the study design (code uf: , register: -a - ). the study was registered on clinicaltrials.gov (identifier no.nct ). clinical parameters were prospectively assessed before, during and after extubation procedure. extubation failure was defined as the need to reintubate less than h after extubation. extubation failure could be due to airway failure, weaning failure or mixed airway and weaning failure. results from december to may , intubation-procedures were studied in patients from centers. patients ( . %) were intubated twice. the median number of intubation-procedures included by center was . the flow chart of the study is shown in fig. . incidence of extubation failure was . % ( of intubation-procedures). incidence of airway failure, weaning failure and mixed failure were respectively . % ( of ), . % ( of ) and . % ( of ). conclusion extubation failure at h occurred in . % of the extubation procedures recorded, % due to airway failure, % to weaning failure and % to mixed airway and weaning failure. specific risk factors will be determined using this multicenter database. introduction acute on chronic liver failure (aclf) have been recently defined by an acute decompensation of a chronic liver disease associated to organ failure and a high mortality rate. few authors reported on the use of total plasma exchange (tpe) in patients with the current definition of aclf. the aim of this pilot study was to evaluate the efficiency and safety of tpe in critically ill cirrhotic patients admitted with aclf in the icu. patients and methods a prospective cohort of cirrhotic patients admitted to the icu between february and february . tpe was performed using a plasma filter (tpe , hospal ® ) on a cvvhdf machine (prismaflex ® , baxter ® ) connected to the patient with a femoral double lumen f catheter. the plasma volume exchanged per session was . - . of the total plasma volume. ratio and type of fluid replacement were % with % albumin solution followed by % with fresh frozen plasma. clinical and biological parameters, and the following scores meld, sofa, clif-sofa, clif-of and child pugh were evaluated prior, after tpe session and days distant of treatment. results seven male patients with a mean age of . ± . years comprised the study and had a total of tpe sessions. the etiology of cirrhosis was alcoholic (n = ) or post-hcv (n = ). the reasons of aclf were acute alcoholic hepatitis (n = ), variceal bleeding (n = ) and sepsis (n = ). prior to tpe, the mean scores of sofa, clif-sofa, clif-of, meld and child-pugh were respectively . , , . , . and c . . mean total bilirubin prior and after tpe sessions was reduced from . ± . µmol/l to . ± . µmol/l (reduction of . %; p = . e− ); at day , mean total bilirubin was still lower at ± µmol/l (p = . ). mean inr prior and after tpe improved from . ± . to . ± . (reduction of inr of . %, p = . e− ) and at day of treatment at ± . (reduction of %, p = . ). mean ggt levels reduced by . % (p = . ). mean platelet counts ( . ± . g/l) reduced by . % (p = ns). the probability of survival at , and days was . , . and . %. one patient was transplanted and still alive. tolerance during sessions was good similar to cvvhdf. two side effects related to the femoral catheter were observed (bacteremia and hemorrhagic shock post catheter ablation). conclusion this preliminary study of tpe in aclf showed a marked reduction of liver enzymes and improvement in coagulation parameters with a relative good safety. a specific caution should be undertaken regarding catheter related complications. tpe worth to be fig. flow chart of the free-rea study introduction extubation is a key moment for the patient on his way to recovery. extubation failure concerns - % of icu patients and is closely linked to nosocomial pneumonia. the practice concerning enteral feeding interruption at time of extubation has not been investigated. fasting before extubation may prevent aspiration and development of nosocomial pneumonia. thus, fasting and gastric content suctioning before extubation may be reasonably considered as a mean to reduce this burden. fasting before extubation may prevent aspiration and development of nosocomial pneumonia. thus, fasting and gastric content suctioning before extubation may be reasonably considered as a mean to reduce this burden. however, fasting, as recommended before elective general anesthesia is likely to be ineffective in the setting of extubation in the icu, due to patients' gastroparesis and prolonged gastric stasis. beyond the potentially unnecessary burden in terms of paramedical workload, fasting may have some side effects such as caloric deficit, hypoglycemia, or delayed extubation. given the current lack of objective data concerning the clinical practice of feeding/fasting and gastric tube suctioning before extubation in the icu, we undertook this descriptive study to assess current practice. materials and methods we conducted a retrospective, multicenter study in eleven intensive care units in the west of france over a month timespan. all patients extubated were included and data about enteral feeding during the peri-extubation period as well as extubation failure and nosocomial that pneumonia occured within days were recorded. data observed in the eleven participating centers were completed with a short email survey concerning declarative practice performed among intensive care units. results during the study period, patients were included. overall, patients ( %) failed extubation and needed reintubation within the days following planned extubation. pneumonia was significantly more frequent reintubated patients than the other ( vs. %, p < . ). hundred patients ( %) received enteral feeding at the time of extubation. compared to patients who did not receive enteral feeding, those patients had a higher disease severity (sapsii score , [ ; ] vs. [ ; ], p < . ; longer duration of mechanical ventilation [ ; ] vs. . [ ; ] days, p < . ). accordingly, those patients had a higher rate of extubation failure ( vs. %, p = . ) and pneumonia ( vs. %, p = . ). among the patients receiving enteral feeding, fasting was implemented before extubation for patients ( %). similarly, the incidence of pneumonia was not different between groups (n = ( %) vs. n = ( %), p = . ). after extubation, the fasting patients experienced a longer delay until feeding resumption as compared to non-fasting patients ( h [ ; ] vs. [ ; ] ), but this difference did not reach statistical significance. overall gastric content suctioning before extubation was not commonly performed; before extubation: % of the fasting patients and % of the non fasting patients. among the participating centers, while some centers imposed a fasting period before extubation to all their patients, some did it infrequently. however, no center never imposed fasting, illustrating between and within center heterogeneity. this heterogeneity was confirmed on the larger scale declarative email survey ( % response rate amont units) which showed that only % of the units had a written standardized operational procedure for extubation. survey respondents reported to practice fasting before extubation "always", "frequently" and "never or rarely" in respectively , and % of cases. conclusion both practices, fasting as well as pursued nutrition until extubation are commonly performed in icus, with little standardization of practice. safety seems equivalent, as no clinically significant difference in terms of reintubation rate and pneumonia were observed. thus, the equipoise condition appears met to undertake a trial evaluating feeding strategies in the peri-extubation period. introduction noninvasive ventilation (niv) has become a cornerstone for the supportive therapy of acute respiratory failure (arf). survival benefits in chronic obstructive pulmonary disease (copd) and cardiac patients have been demonstrated. although arf and copd patients are at risk of malnutrition that adversely affects patient outcomes, few data are available regarding the management of nutritional support in non-invasively ventilated patients. we sought to describe nutritional management in patients receiving niv as the first line therapy for arf. secondary objectives were to assess the impact of early nutrition use on the need for invasive mechanical ventilation, occurrence of icuacquired pneumonia, length of stay, and death. patients and methods we conducted an observational study from the multicenter french database fed by french icus. our institutional review board approved this study. adult medical patients admitted to the icu and receiving niv for more than days were included. exclusion criteria were patients admitted after surgery, readmitted in icu, patients with neuromuscular disease and treatment-limitation decisions on admission. four groups of patients were defined according to nutrition received during the first days of niv: ( ) no nutrition; ( ) enteral nutrition: patients who received enteral nutrition with or without parenteral nutrition; ( ) parenteral nutrition only ( ) oral nutrition only. the impact of nutrition on day- mortality was assessed through the use of a cox model adjusted on clinically relevant covariates. the impact of nutrition on other secondary end-point i.e. icu-acquired pneumonia occurrence, need for invasive mechanical ventilation were assessed using a fine & gray models. patients were censored after days of follow-up. choice among collinear variables was performed considering clinical relevance, rate of missing variables and reproducibility of definitions. results were given as hazard ratio (hr) for cox models and subdistribution hazard ratios (shr) and % confidence intervals (ci). the impact on duration of stay was estimated by a multivariate poisson regression. p values less than . were considered as significant. statistical analysis was performed using sas . (cary, nc). results during the study period, , patients were included in the database and met inclusion criteria. among them, received no nutrition; received enteral nutrition, received parenteral nutrition only, and received oral nutrition only. overall, patients developed icu-acquired pneumonia ( %), required invasive mechanical ventilation ( . %) and died before day- ( %). median length of stay was days [ ; ]. after adjustment for confounders, type of nutrition support was associated with an increase day- mortality (p = . ). compared to oral nutrition, enteral nutrition was associated with an increase day- mortality [shr . , % ci . - . ; p = . ] whereas parenteral nutrition and no nutrition did not influence this outcome. the type of nutrition was not associated with the occurrence of icu-acquired pneumonia (p = . ). however, patients who received enteral nutrition experienced more frequently icu-acquired pneumonia [shr = . , % ci . - . ; p = . ] as compared to oral nutrition patients. ventilator free days within the days were negatively associated with the type of nutrition (p < . ). compared to oral nutrition, parenteral and enteral nutrition were negatively associated with ventilator free days within the days [rr per day = . , % ci . - . ; p < . and rr per day = . , % ci . - . ; p < . ]. delta paco measured between the first days was not associated with any type of nutrition. conclusion more than half the patients receiving niv were fasting within the first two niv days. oral nutrition was prescribed for onethird of them and was well tolerated. lack of feeding or underfeeding had no impact on mortality and ventilator free days within the days. however, enteral nutrition was associated with an increased occurrence of icu-aquired pneumonia and a higher mortality rate. was high, caloric debt during temporary ecls was low in comparison with previous results [ ] . overnutrition was frequent in the nec group and would justify implementation of nutrition protocol. incidence of gi intolerance remains frequent and could justify systematic used of motility agents with introduction of en. conclusion enteral nutrition in patients treated with temporary extracorporeal life support is feasible and may be improve with systematic motility agents and implementation of nutritional protocol. introduction cardiac surgery with cardiopulmonary bypass (cpb) is associated with a generalized inflammatory response with concomitant immune paresis which predisposes to the development of postoperative infections and sepsis ( ) . lymphocytes are essential agents of innate and adaptive immune responses during infections or inflammation processes. lymphopenia has been associated with immune dysfunction during septic shock, and it has been shown that low absolute lymphocyte count was predictive of postoperative sepsis ( ) . furthermore, impaired lymphocyte function probably occurs after cpb. thus, we investigated mechanisms involved in postoperative lymphopenia and impaired lymphocyte function after cpb. the aims of this study were: ) to describe a potential relationship between lymphopenia and occurrence of postoperative infections. ) to demonstrate that cpb induces lymphocytes apoptosis. ) to demonstrate that cpb impaired lymphocyte function (ability to proliferate). ) to demonstrate that il- , pd-l (programmed cell death ligand ) and indoleamine , -dioxygenase (ido) could be interesting targets to restore lymphocyte ability to proliferate after cpb. patients and methods blood cell counts with differentials obtained within the first postoperative week were analyzed in patients undergoing cardiac surgery in . postoperative lymphopenia was defined as a lymphocyte count < . × cells l − . postoperative infections were defined following cdc criteria. study procedures: the following analysis were performed before (t ) and h after (t ) cardiac surgery with cpb: lymphocyte apoptosis; t-cell proliferation ability following polyclonal stimulation; hla-dr and pd-l expression on monocytes; plasma ido activity and il- levels; and the ability of lymphocytes to undergo a clonal proliferation when stimulated using specific inhibitors of il- and ido. the study was approved by our local ethics committee. patients were informed of the observational nature of the study and gave their consent. . early lymphopenia after cpb was associated with the occurrence of postoperative infection: postoperative infections occured with a median delay of days. patients who developed postoperative infections had a significantly lower lymphocyte count at day , day and day than patients without postoperative infections. . cpb induced lymphocyte apoptosis and decreased t-cell proliferation ability. . cpb during cardiac surgery decreased mhla-dr expression. . cpb increased ido activity, pd-l expression and il- plasma levels. . il- or pd-l inhibition of inhibition could restore ability of lymphocytes to proliferate, although ido inhibitors did not show any effect. we provided new evidences that cpb induces immunosuppression. we also demonstrated that il- and pd-l could be interesting targets to restore ability of lymphocytes to proliferate. as maintaining mv during cpb decreased plasmatic levels of il- , our study brings new evidences that ventilator strategies could be of interest to decrease postoperative infections. respectively . % (n = ), . % (n = ) and . % (n = ) of the included patients. mortality was of . % in the overall population (n = ) and was higher in neutropenic patients ( . vs. . % in non-neutropenic patients; p < . ). neutropenia was independently associated with poor outcome when adjusted for underlying malignancy, allogeneic stem cell transplantation and severity as assessed by organ support (or . ; % ci . - . ). mortality decreased progressively over time in both non-neutropenic (from to %; p < . ) and in neutropenic patients (from to %; p < . ). when adjusted for confounders, admission during a more recent period was independently associated with favourable outcome and did not change the final model. conclusion this preliminary analysis suggests a meaningful survival in neutropenic critically ill cancer patients despite an independent association between neutropenia and mortality. additional analyses are on-going in order to adjust for study weight, heterogeneity across studies, assess the influence of neutropenia duration or g-csf use, and confirm the influence of neutropenia in a predefined subgroup of patients. introduction candida bloodstream infections (cbi) are frequent and increasing in hospitalized patients, especially in intensive care units. considering the results of some experimental in vitro and animal studies, it seems that yeasts belonging to candida genus are able, so as to survive, to modulate the immune response of the host by guiding t cells polarization to th profile. th and th cytokines are known to be involved in host defense against cbi. however, these data are mainly experimental or collected after candidemia. the aim of this study is to precise kinetic of cytokines network during human cbi. this was an ancillary study of an institutional project dedicated to pathophysiology of candidiasis. we have included patients with candidemia and controls ( matched hospitalized controls and healthy subjects). the sera of cases were gathered before (almost days before), during and after the isolation of yeasts from blood culture, defined as day (d ). quantitative analysis of cytokines by luminex ® technology and of ( , )-β-d-glucans by fungitell ® test were performed on samples. the amplitude of th profile response was expressed by summing the amount of the most relevant cytokines for th , th and th profiles, in pg/ ml. for each patient, the highest level of response was considered as %. results are expressed for the population by means of the results. we then performed univariate analysis (fischer exact test for qualitative variables, mann-whitney and wilcoxon test for quantitative variables, spearman for correlation; graphpad prism v software) and a multidimensional analysis by principal component analysis (pca; igorpro software). results patients with candidemia exhibited an increase in proinflammatory cytokines (ifnγ, tnfα and il- ), in comparison with the anti-inflammatory cytokines (il- and il- ) before d (p = . ) in univariate analysis. the ratio between mean values reverses at d and d (p = . ) and the increase of th response level from d to d is correlated to the decrease of th response (r = − . ; p = . ) in univariate analysis and pca. a pro-inflammatory response (th ) is associated with a reduced mortality (rr = . [ . ; . ]) and with a lower β-d-glucans levels (p < . ). discussion we describe here a dynamic cytokine profiles in response to candidemia. pro-inflammatory response predominates before d and reverses after. this is contradictory to the postulate that an antiinflammatory background could predispose to invasive candidiasis in icu patients and exhibiting a "post-infectious immune suppression conditions". but the relative deficiency in th response compared to simultaneous anti-inflammatory cytokines secretion observed after cbi is in accordance with experimental data, suggesting the modulation of the immune response by candida. the link between cytokinic profile and mortality can also raise the hypothesis of an influence by genetic factors on the regulation and direction of the immune response and so, the existence of a high-risk population. conclusion these data suggest a relation between candida and the orientation of the immune response towards a pattern deleterious for the infected host. this could allow to determine the most relevant cytokines varying during cbi. they could be used as biomarkers to identify the patients who could benefit from an early treatment in a preemptive targeted therapeutic strategy. these data will be paralleled to genetic background and to circulating candida derived molecules to precise the relative part of the host and the pathogen in this complex interaction. introduction lung ultrasound is widely used in intensive care, ermergency and pneumology medicine, for assessing acute respiratory pathologies. it is noninvasive, radiation free and rapidly available at the patient's bedside and provides an excellent accuracy. so, lung ultrasound may be an interesting tool for the physiotherapist as it allows to assess with more accuracy the patient improving the chest physiotherapy indication and monitoring ( ) . as far as we are aware, no study has evaluated the impact of lung ultrasound on clinical-decision making by physiotherapists in the use of chest physiotherapy. this case report highlights the lung ultrasound interest in chest physiotherapy in patient with lung consolidation. patients and methods this was a case report written following the recommendations of the care guideline ( ). the case was a -years-old female patient, non intubated, hospitalized in a respiratory icu. she was hypoxemic (pao = mmhg and sao = %), with dyspnoea at rest and an increasing radiological opacity at the right lung base. hypoxemia was the indication for physiotherapist referral. at the clinical examination, the physiotherapist's findings were: decreased mobility, dullness and abolished vesicular sound at the base of right hemithorax. this clinical examination and chest x-rays analysis allowed the physiotherapist to propose several clinical hypotheses: pleural effusion, obstructive atelectasis or pneumonia. the chest physiotherapy treatment differs according to the type of lung deficiencies. for example, the physiotherapist must to refer the patient to the medical staff in case of pleural effusion or may implement hyperinflation technique in case of obstructive atelectasis. determining the nature of lung deficiencies is essential to provide the more suitable therapeutic strategy. so, the physiotherapist decided to perform a lung ultrasound examination to retain the more likely hypothesis. results ultrasound examination performed by the physiotherapist highlighted the presence of a lung consolidation at the infero-lateral and posterior parts of the right lung with a pneumonia pattern: presence of tissue-like sign, shred sign, dynamic air bronchogram and fluid bronchogram. the medical staff implemented antibiotic treatment. the ultrasound findings guided the physiotherapist to choose chest physiotherapy technique improving the alveolar recruitment: nearly prone position (left side down) and continuous positive airway pressure during min. the patient response to the treatment was monitored by ultrasound and showed a decrease of the lung consolidation size and apparition of b lines, meaning a gain of lung aeration. these findings were associated with spo improvement but without decrease of dyspnoea. discussion lung ultrasound allowed the physiotherapist to precise the nature of the radiological lung opacity. as it is more accurate than clinical examination or chest x-ray, this suggests a more suitable choice of chest physiotherapy techniques than conventional clinical decision-making process. ultrasound findings suggested a positive response to the chest physiotherapy treatment. the apparition of re-aeration signs (b lines, decreased consolidation size) showed a short-term efficacy of the chest physiotherapy treatment. this allowed the physiotherapist to continue the treatment during week and obtain a substantial clinical improvement. conclusion the use of lung ultrasound in the clinical decision-making process may help the physiotherapist to choose with more accuracy the therapeutic strategy. moreover, it allows to monitor the treatment in real-time and assess the patient's response. the use of this tool may allow the physiotherapist to determine the optimal indications for chest physiotherapy and thus avoid unnecessary or inappropriate treatments. introduction critical illness together with immobilization have deleterious effects on patients outcome, especially in the presence of sepsis. increased muscle catabolism and membrane inexcitability reduce muscular mass and impair function within the first days after sepsis onset ( ). early mobilization could potentially limit muscle wasting and functional impairment in this population. the purpose of this study was to test whether exercise during the early phase of sepsis is safe and beneficial and to which extent it can limit skeletal muscle protein catabolism and preserve function. patients and methods adult patients admitted with the diagnosis of severe sepsis were included and randomly allocated to two groups; ) control group (ctrl-g): manual passive/active manual mobilization twice a day or ) experimental group (exp-g): additional two times min of passive/active cycling exercise. both groups benefited from a reduced sedation, adjusted nutritional intake and bed to chair transfer as soon as possible. skeletal muscle biopsy and electrophysiological testing were realized at day- and day- . muscle histology, biochemical and molecular analyses of anabolic/catabolic and inflammatory signalling pathways were performed. a group of four healthy subjects was used to obtain non pathological values. hemodynamic parameters and patients perception were collected during each session. results twenty-one patients were included, however died before the second muscle biopsy. ten patients in ctrl-g and nine in exp-g were finally analysed. muscle fibre cross sectional area (µm ) was significantly preserved by exercise (relative changes were ctrl-g: − ± % vs exp-g: ± %, p = . ). markers of catabolic systems were highly increased during sepsis compared to healthy subjects and reduced in both groups days after admission. however the reduction in mrna (relative change) tended to be more important in exp-g: murf- (ctrl-g: − ± % vs exp-g: − ± %, p = . ), mafbx (ctrl-g: − ± % vs exp-g: − ± %, p = . ), lc b (ctrl-g: ± % vs exp-g: − ± %, p = . ) and bnip (ctrl-g: ± % vs exp-g: − ± %, p = . ). anabolic and inflammatory markers were not affected by exercise. electrophysiological testing, including direct muscular stimulation, was abnormal on day- in of evaluated patients. since only a limited number of patients could be reassessed a second time, comparison between groups was not possible. in general, all activities were well tolerated by patients with no adverse events. the pulmonary auscultation is used by respiratory therapist (rt) to evaluate the efficiency of a treatment. listen to the noises coming from the primary bronchi (pb) is important because it is the place where secretions can be accumulated. therefore, it is crucial to know exactly where to place the stethoscope's chestpiece on the chest. few studies have analyzed the chest area where the pb were located. our hypothesis is that pb are localized on a line that joins axillary fossa (bi-axillary line: bal). the aim of our study is to evaluate the probability to find the primary bronchi by analysis of chest radiography. patients and methods a retrospective study was performed by analysis of chest x-ray using the software: tm reception ® , which allows precise measures to the tenth of millimeter. all the x-rays were made on confined to bed patients hospitalized within intensive care unit, internal medicine and abdominal surgery rooms. the following measures (in mm) were made between: the exclusion criteria were: bmi < . kg/m and bmi > kg/m , scoliosis, minor patient, lack of visibility of one of the axillary fossa, lack of visibility of pb, clavicular asymmetry, kyphosis, lack of symmetry in the shot, atelectasis and pneumothorax. statistics: normality test: ks. mean values are expressed with their sd and % ci. discussion in this study, we performed analysis of chest x-rays of bedridden patients and we demonstrated that it is possible to localize easily, on either side of the bs, the right and left pb at ± mm distance (lp) above a line joining axillary fossa. this study constitutes a new tool for the rt who, by using stethoscope with a chestpiece of cm surface area, will be able to listen to noise coming from pb. conclusion the data presented herein (fig. ) show that right and left pb are located at a mean distance of (± ) mm and (± ) mm above the bal, on both sides of the bs. the bal represents thus an easy and precise mode to detect right and left pb by bedridden. finally, the distance between the hyoid bone and the sc is about cm. as the pb are located after the bifurcation, this information constitutes another useful way for the localization the right and left pb by bedridden patient. introduction critically ill patients frequently develop muscle weakness, which is associated with prolonged intensive care unit and hospital stay ( ). this randomized controlled trial (clinical trials nct ) was designed to investigate whether a daily training session using a tilt table, started early in stable critically ill patients with an expected prolonged icu stay, could improve strength at icu and hospital discharge compared to a standard physiotherapy program. the study protocol was approved by an ethics committee and informed consent was obtained from all patients. patients admitted in adult icu of marie lannelongue hospital, france, who were mechanically ventilated for at least days were included. exclusion criteria were cerebral or spinal injury, pelvic or lower limb fracture. patients were assessed each day for temporary contraindications for mobilization out of bed (rass score <− or > ; hemodynamic instability; a continuous intravenous dose of epinephrine/ . no significant difference was observed in terms of mrc score or in terms of pts with or without weakness (mrc > ) at icu or hospital discharge. however, the number of pts with weakness was significantly higher in the group before tilt mobilization, suggesting a more rapid improvement in the tilt group. the icu and hospital lengths of stay were not different between groups. discussion the prevalence of muscle weakness in our population is high before mobilization ( . %, % ci . - . ), is still . % at icu discharge but represents only ~ % at hospital discharge. this low hospital discharge prevalence is probably related to the early and intense physiotherapy in both groups, which may explain our inability to demonstrate superiority of the addition of tilt table positioning, although a faster recovery is suggested. conclusion training sessions using a tilt table, in addition to early and intense physiotherapy did not improve muscle strength evaluated using mrc score in surgical icu patients with muscle 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identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the macocha score in a multicenter cohort study faouzi saliba -faouzi.saliba@pbr.aphp.fr annals of intensive care réanimation médicale polyvalente, hôpital de la source mickael landais -mickaelandais@gmail.com annals of intensive care perioperative fasting in adults and children: guidelines from the european society of anaesthesiology the decision to extubate in the intensive care unit service de réanimation médicale s refeeding hypophosphoremia in a medical critical care unit: -month observational study gioia gastaldi -gioia.gastaldi@chu-rouen.fr annals of intensive care refeeding hypophosphatemia in critically ill patients in an intensive care unit. a prospective study refeeding syndrome: problems with definition and management biosit and inserm u , faculte de medecine, université rennes immune dysfunction after cardiac surgery with cardiopulmonary bypass: beneficial effects of maintaining mechanical ventilation s influence of neutropenia on mortality of critically ill cancer patients: results of a systematic review on individual data quentin georges brazil; department of critical care medicine and division of pulmonary and critical care medicine united kingdom; department of intensive care centre d'infection et d'immunité de lille equipe -basic and clinical immunity of parasitic di delta nlr") were calculated. statistical analysis used appropriate non parametric tests and cox regression for survival analysis. the ability of the variables to discriminate survivors from non-survivors was determined using roc curves results during the study period, cirrhotic patients were admitted in icu. the etiologies of liver cirrhosis were alcoholic in % of cases with severe score: median child-pugh score = %) deaths after icu discharge during the same hospitalization. nlr decreased for survivors between d and d univariate analysis, for predicting survival, higher values of nlrd , delta nlr, meld score at admission, sofa score at admission and at day and delta sofad -d were significant factors. predictors of death in multivariate analysis are shown in fig. . area under delta nlr roc conclusion the blood nlr is a novel inflammation index that has been shown to independently predict poor clinical outcomes. we have demonstrated that delta nlr is an independent predictor of mortality in critically ill cirrhotic patients the association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study gene-and exon-expression profiling reveals an extensive lps-induced response in immune cells in patients with cirrhosis celine dupre -duprecece@gmail.com annals of intensive care diagnostic accuracy of procalcitonin in critically ill immunocompromised patients the role of pattern-recognition receptors in innate immunity: update on toll-like receptors esm- is a novel human endothelial cell specific molecule expressed in lung and regulated by cytokines thoracic ultrasound: potential new tool for physiotherapists in respiratory management. a narrative review the care guidelines: consensus-based clinical case reporting guideline development department of physical medicine and rehabilitation icu-acquired weakness and recovery from critical illness o where should we place the stethoscope's chestpiece to hear the noise of the primary bronchi? frédéric duprez , bastien dupuis , grégory cuvelier , thierry bonus frédéric duprez -dtamedical@hotmail.com annals of intensive care o aerosol delivery using two nebulizers through high flow nasal cannula: a randomized cross-over spect-ct study correspondence: jonathan dugernier -jonathan.dugernier@uclouvain.be annals of intensive care introduction in , an international consensus conference took stock of the various measures to be implemented for the prevention of ventilator acquired pneumonia (vap) [ ]. these measures are often gathered in groups of or under the term of "ventilator-bundle. " the effectiveness of these "bundles" was poorly evaluated in african environment. objective to establish a vap prevention program and assess its impact on morbidity and mortality of patients under mechanical ventilation in our service. patients and methods prospective, mono centric, quasi-experimental before-after study. it took place in the intensive care unit of the university clinics of kinshasa in the democratic republic of congo (drc). this service is equipped with beds and a respirator for two beds. the observational period (phase ) was carried out from february st to december st, and the intervention period (phase ) from february st, to february st, . all consecutive patients intubated and mechanically ventilated for more than h were included. five preventive measures were held: hand hygiene, the elevation of the head of the bed at °- °, the daily lifting of sedation, oral decontamination with chlorhexidine and control cuff pressure of the endotracheal tube. compliance with this bundle was assessed by direct observation without the knowledge of caregivers. the diagnosis of "vap" was held before a clinically modified sore (m cpis) > . the main outcomes were the incidence of vap and mortality. the protocol for this study was approved by the ethics committee of the school of public health of the university of kinshasa, under the approval number: esp/ec/ / .introduction nosocomial infections (ni) are common in burn patients due to the loss of the first line of defense against microbial invasion, immunocompromising effects of burn injury, and invasive diagnostic and therapeutic procedures. the objective of this study was to identify the incidence of nosocomial infection (ni), the pathogens and their antibacterial patterns, and prognosis of these burn patients. patients and methods a retrospective study was conducted in a bed intensive burn care unit during months. patients were eligible for the study, if they met the following criteria: total burn surface area (tbsa) > %, length of icu stay ≥ h, and infected in accordance with the criteria of the national nosocomial infections surveillance (nnis) and the criteria of the sfetb [ ][ ]. in this study, nis were classified into four main groups: pneumonias, bloodstream infections (bsi), catheter related infections (cri), and urinary tract infections (uti). for included patients, skin levy, blood cultures, urine and sputum cultures were drawn during fever or clinical features of sepsis. results during the -month study period, patients were admitted to the icu, patients were included ( . %). were male and female. the mean age was ± yr. the mean tbsa was ± %. % were admitted from another hospital. burn injuries were due to domestic accidents in % and self immolation in %. the mean none. none. none. none. none. none. none. none. none. none. ann. intensive care , (suppl ): none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. consulting activities with fisher & paykel. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. none. failure extubation in intensive care unit: risk factors, incidence and evaluation of a mechanical ventilator weaning protocol lucie petitdemange , anne sophie guilbert none. none. none. none. none. none. opportunistic infections in patients with solid tumors: a systematic review julien poujade , elie azoulay none. invasive aspergillosis in non-immunocompromised patients hospitalized intensive care unit guillaume trumpff , max guillot , thierry braun , ralf janssen-langenstein , marie-line harlay , jean-etienne herbrecht introduction characteristics and outcomes of adult patients with invasive aspergillosis in intensive care unit have rarely been described. we performed a retrospective study on consecutive adult patients with invasive aspergillosis who were admitted form january through january to the intensive none. noorah zaid , nawel ait-ammar , christine bonnal , jean-claude merle , francoise botterel , eric levesque anesthesia and intensive care medicine, chu henri mondor, créteil, france; unité de parasitologie-mycologie, département de virologie, bactériologie-hygiène, parasitologie, hopital henri mondor, créteil, france correspondence: eric levesque -eric.levesque@aphp.fr annals of intensive care , (suppl ):s introduction liver transplant recipients have high rate of invasive fungal disease (ifd) with high morbidity and mortality, in part due to its delayed diagnosis. the fungal cell wall component ( , )-betad-glucan (bg) is a biomarker for fungal infection but its utility remains uncertain. this prospective study was designed to review our experience in ifd and to evaluate the impact of bg in the diagnosis of ifd. patients and methods from january to may , liver transplantation were performed in our institution. serum samples were tested for bg (fungitell; cape cod inc., usa) least weekly between liver transplantation and their discharge from hospital. ifd was defined as proposed by the european organization for research and treatment of cancer/mycoses study group. results nineteen patients ( %) were diagnosed with ifd including cases of candidiasis infection (ci) in eleven out of patients, invasive pulmonary aspergillosis (including one who had previously ci) and one case of septic arthritis of the hip caused by scedosporium spp. ifd was associated with significantly high mortality (log-rank p = . ). the area under the roc curves, for bg to predict ifd, was . ( % ci . - . ). using a cutoff of pg/ml, the most discriminative cut-off point from the roc curve, the sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) values of bg for overall ifd was % ( % ci, - ), % ( % ci, - ), % ( % ci, - ) and % ( % ci, - ). conclusion based on its high npv, bg value appears to be a good biomarker to rule out the diagnosis of ifd when the value is below pg/ml. a single point bg may guide the investigation and the decision to start antifungal therapy in patients at risk for ifd. none. monitoring of changes in lung and chest wall mechanics in the supine, lateral and prone positions during the prone positioning maneuver in ards patients zakaria riad , mehdi mezidi , hodane yonis , mylène aublanc, , sophie perinel-ragey, , floriane lissonde , aurore louf-durier, , romain tapponnier , jean-christophe richard , bruno louis, , claude guérin , plug working group réanimation médicale, hôpital de la croix-rousse, lyon, france; inserm, u , equipe , équipe biomécanique cellulaire et respiratoire, université paris-est créteil -faculté de médecine, créteil, france correspondence: zakaria riad -zakaria.riad@icloud.com annals of intensive care , (suppl ):s none. introduction systemic rheumatic diseases (srd) are autoimmune diseases that are rare but cause substantial morbidity and mortality. srds chiefly affect the lungs, however, data on critically ill patients with srd admitted for arf are scarce. patients and methods retrospective cohort conducted in french icus ( . the major comorbidities were cardiovascular ( %), tobacco exposure ( %), chronic kidney disease ( %) and neoplasia ( %). two-thirds of patients were on systemic corticosteroids at admission, the median dose of (iqr) mg per day. srd diagnosis was made in the icu in . % of patients. clinically or microbiologically documented bacterial pneumonia was the leading arf etiology ( . %). in % of cases, arf was related to an opportunistic infection (mainly aspergillus (n = ) and pneumocystis (n = )). others arf etiologies included specific lung involvement ( . %) and cardiac pulmonary edema ( . %). sofa on day one was [ ] [ ] [ ] [ ] [ ] [ ] [ ] . associated organ dysfunctions were mainly hemodynamic ( %) and renal ( %). mechanical ventilation was needed in % of patients (non invasive only in . % or invasive in . %), % needed vasopressors, and % renal replacement therapy. systemic corticosteroids were started in % of patients and % of patients received pulse steroids. cyclophosphamide and plasma exchange were required in and % of patients, respectively. length of icu stay was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days. icu-acquired infection occurs in % of cases. in total, patients ( . %) died throughout the icu stay. arf etiology was not associated with mortality. by multivariate analysis, shock on admission (or . [ . - . ], p < . ) and the use of invasive mechanical ventilation (or . [ . - . ], p = . ) were independently associated with mortality, whereas non-invasive ventilation was associated with decreased mortality (or . [ . - . ], p = . ). by considering among the connective tissue diseases, the groups of myositis and scleroderma (n = ), these diseases were associated with a trend for a higher mortality (or . [ . - . ], p = . ). conclusion in patients with srd, arf is associated with a high case fatality, primarily when mechanical ventilation is needed. particular attention must be given to specific srd-sub groups for which pulmonary flare may require intensive immunosuppression. none. none. none. severe acute pancreatitis in icu: management and outcomes of infected pancreatic necrosis charlotte garret , matthieu peron , emmanuel coron , cédric bretonnière , jean reignier , christophe guitton réanimation médicale, chu hôtel-dieu nantes, nantes, france; the acute pancreatitis appears as a pathology that we can define with difficulty because of its clinical presentation or prognosis. patients and methods in our study, we analysed cases of acute necrotic and hemorrhagic acute pancreatitis, hospitalized at the department of resuscitation of the surgical emergencies (p ) of the uhc ibn rochd casablanca during the period ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the purpose of this study is to do a descriptive analysis of the epidemiologic, clinic, radiological, therapeutic and evolutive data of the acute necrotic pancreatitits, we included in our study patients with epidemiologic, clinic, radiologic, biologic criteria of acute necrotic pancreatitits diagnosis whatever is the biliary or alcoholic etiology. the valuation gravity of the pancreatitis has been based on:• ranson bioclinical score > /apache ii > ; • visceral failure.• spreading of the necrosis. the analysis of the results shows that: about the epidemiologic aspect: mean age ( year old), the biliary etiology predominates ( %). about the clinical aspect: pain ( %) vomiting ( %), stop of the transit ( %), the visceral distresses are: the shock ( %), respiratory distress ( %), and neurological distress ( %). about the radiological aspect: pleural effusion ( %), abdominal echography: vesicular lithiasis ( %), dilated principal biliary duct ( %), abdominal computerized tomography: stage e ( %). about the biological aspect: hyperglycemia ( %), hyper-amylasemia ( %). the indexes of gravity that have been appreciated in this study are: ranson score > ( %), imrie score > ( %), igs score ≥ ( %), osf score ≥ ( %). the treatment of the anhp has been symptomatic in particular and the evolution has been characterized by mortality about %, the cause was particularly infectious. the prognostic factors predetermined in this study are:• female type (p = . ).• hemodynamic distress (p = . ).• respiratory distress (p = . ).• scores of gravity:• ranson > (p = . ).• imrie > (p = . ).• osf ≥ (p = ).• infection (p = . ).• duration of the hospitalization (p = . ).• rate of c-reagent protein (p = . ). in conclusion, the mortality is still high in the anhp, considerable effort of search is necessary to prevent the infectious complications of mortality. none. predicting -day mortality following liver transplantation in patients with acute-on-chronic liver failure: a decision-tree model from the french national liver transplantation system, the optimatch study, - none. none. none. none. none. none. the french law and recent expert opinions have emphasized the need for a multidisciplinary approach in decisions to forgo life sustaining therapies for the critically ill. we sought to assess how icu nurses actually rank their involvement and perceive this process. materials and methods we conducted a cross sectional survey using a web-based questionnaire between june and september . results of the icus invited to participate, ( %) agreed. a total of icu participants completed the survey of whom % were nurses and % assistant nurses. median age was (inter quartile range - ) years and % were female. median work experience was ( - ) years and time in the icu was ( - ) years. eighty-five percent of the participants have been involved at least once in a multidisciplinary end-of-life discussion. less than half of the participants reported a good ( %) or partial ( %) knowledge of the current end-of-life legal framework. the decision to start a discussion about withdraw life-sustaining therapy (wlst) was initiated by a senior intensivist in % of the cases, by a nurse in % and an assistant nurse in . %. this decision was approved by % of the participants. the decision-making process was considered to be initiated at the right time for % of the participants, too late for %, and too early for %. the discussion occurred mostly in the afternoon ( %) or during the medical staff ( %), in a dedicated place in % of the cases. a median of ( - ) health-care professionals attended the wlst discussion. half the respondents reported being reluctant to talk during the discussions and % never expressed their own opinion. indeed, although the length of the discussion was ( - ) minutes, participants estimated to talk during only ( - ) minutes. the following reasons were mentioned by the participants to explain these facts: having cared for the patient for too short time ( %), lack of medical knowledge ( %), decision of wlst already taken by the medical staff ( %), their opinion not really taken into account ( %), reluctant to talk during meetings in general ( %), consider that the discussion is limited to a medical expertise ( %), limited professional experience ( %), and fear to express a different opinion ( %). nevertheless, % of the participants were partially ( %) or totally ( %) satisfied by the way the decision making process was conducted, % considered that collegiality was applied, and % agreed with the final decisions.conclusion icu nurses rank favorably multidisciplinary wlst discussions. nevertheless their involvement in the discussion remains limited. beyond factors related to work organization and professional experience, efforts should be made to recognize their role and value, and to encourage them to share their own opinions with the other members of the icu team. none. determinants and prognosis of elevation of high-sensitivity cardiac troponin t in patients hospitalized with vasodilatatory shock marie caujolle , jérôme allyn , dorothée valance , caroline brulliard , none. free plasmatic mitochondrial dna-receptor for advanced glycation end-products: a new signaling pathway of critical illness-induced endothelial dysfunction arthur durand , rémi nevière , florian delguste , eric boulanger, none. quality of reporting of fluid responsiveness evaluation studies: a five year systematic review izaute guillame , matthias jacquet-lagrèze , jean-luc fellahi none. none. none. none. none. introduction microaspiration of gastric and oropharyngeal contaminated secretions occurs frequently in intubated critically-ill patients, and plays a major role in the pathogenesis of ventilator-associated pneumonia (vap). at basic state, patients with chronic obstructive pulmonary disease (copd) have an increased risk of microaspiration (due to gastro-esophageal reflux disease, pharyngo-laryngeal dys-function…), this risk may even be more important under mechanical ventilation. the main purpose of this study is to determine if copd is a risk factor for global abundant microaspiration (gam) in intubated critically-ill patients. we gathered data about two prospective multicentric randomized trials focused on microaspiration in intubated patients. data about copd were retrospectively collected in order to complete previous data. microaspiration of gastric and oropharyngeal secretions was respectively determined by quantitative measurements of pepsin and salivary amylase in all tracheal aspirates during the first h after intubation. gam was defined as the presence at significant level of pepsin (> ng/ml) and/or salivary amylase (> ui/l) in at least % of the tracheal aspirates. in order to find gam independent risk factors, we realized an univariate and multivariate analysis of the variables collected. results out of patients included in the studies, were analyzed among which patients with copd. patients ( %) had gam. neither copd diagnosis, nor spirometric severity nor specific therapeutics were associated with gam. risk factors for gam in univariate analysis were the age, diabetes, low score in glasgow coma scale (gcs), and no recourse to paralytic agents or vasopressors. after none. none. implementation and impact assessment of a "ventilator-bundle" at the university clinics of kinshasa: before and after study josé mavinga , joseph nsiala makunza , m e mafuta , yves yanga , amisi eric , jp ilunga , ma kilembe none. none. amel mokline , achraf laajili , helmi amri , imene rahmani , nidhal mensi , lazheri gharsallah , sofiene tlaili , bahija gasri , rym hammouda , amen allah messadi burn care department, trauma and burn center, tunis, tunisia correspondence: amel mokline -dr.amelmokline@gmail.com annals of intensive care , (suppl ):s none. none. none. introduction mechanical ventilation (mv) weaning is a crucial step in critically ill patients. mv duration is associated with an increased risk of ventilator associated events, even though its specific impact on mortality has never been clearly demonstrated ( ). automated closed loop systems might help the weaning process. a recently published meta-analysis has reported a reduction in mv duration when using an automated weaning mode as compared to non-automated mode ( ) . however, the different automated modes have not been compared to each other. the objective of this network meta-analysis was to compare the performance of the three major automated weaning modes, i.e. the automode°, the smartcare° and the adaptative support ventilation (asv°) for mv weaning in critically ill and postoperative adult patients. we included all randomised control trials that compared automated closed loop weaning applications either to another automated application or standard care, including weaning according to a written weaning protocol or nurse driven protocols. the three modes of automated modes included in the study were asv°, smartcare° and automode°. the primary outcome was the duration of mv weaning, defined as the time between randomization and a successful extubation. we also planned subgroup analyses in the icu and the post-operative populations. the quality of the studies was assessed independently by two blinded investigators, using the evaluation recommended by the cochrane collaboration. a network bayesian meta-analysis using random effect models and based on aggregate data from the included studies was performed using the gemtc package (r project, vienna). this trial was declared in pros-pero in august (crd ). results search of databased identified articles; were screened for eligibility after removal of duplicates. abstract analysis led to the exclusion of articles with a final full text analysis of randomised control trials. ultimately, trials were included in the analysis, representing ventilated patients. nine studies included patients in the post-operative period while six were conducted in icu. the automated mode was asv° (a) in studies, smartcare° (c) in studies and auto-mode° (b) in studies. all studies reported the duration of mv weaning as defined in our protocol. in all studies, the control group was standard care with a weaning process driven either by nurses or physicians. in studies ( %) a written weaning protocol was used in the control group. all icu studies used sedation protocols based on sedation scores, none of them including systematic daily sedation interruption. each one of the automated application was associated with a significant reduction in the duration of mv as compared to the control. when comparing all different modes using the network meta-analysis framework, asv° appeared to be the best automated mode when it pertains to reducing the duration of mechanical ventilation weaning (fig. ) . subgroup analysis showed similar results in the post-operative and the icu populations. conclusion compared to standard weaning practice, the major automated weaning modes significantly reduced the duration of mv weaning in critically ill and post-operative adult patients. asv° was associated with the most significant effect when compared to the two other automated modes (smartcare°, automode°). further physiological respiratory studies would help to understand the underlying mechanisms accounting for the superiority of asv. none. none. introduction in intensive care unit (icu) patients, diaphragm dysfunction is associated with adverse clinical outcomes. ultrasound measurements of diaphragm thickness (tdi), excursion (exdi) and thickening fraction (tfdi) have been proposed as estimators of diaphragm function, but have never been compared to phrenic nerve stimulation. our aim was to describe the relationship between tdi, exdi, tfdi and diaphragm function evaluated using the change in endotracheal pressure after phrenic nerve stimulation (ptr,stim), and to compare their prognostic value. patients and methods ptr,stim and ultrasound variables were measured in mechanically ventilated (mv) patients < h after intubation ("initiation of mv", under assist-control ventilation, acv) and at the time of switch to pressure-support ventilation ("switch to psv"). diaphragm dysfunction was defined as ptr,stim < cmh o. results patients were included. at initiation of mv, ptr,stim was not correlated to tdi (rho = − · , p = · ), exdi (rho = · , p = · ) or tfdi (rho = − · , p = · ). at switch to psv, tfdi and exdi were correlated to ptr,stim, (rho = · , p < . and · , p = · , respectively), but tdi was not (rho = − · , p = · ). at switch to psv, a tfdi < % could reliably identify diaphragm dysfunction (sensitivity and specificity of and %, respectively), but tdi and exdi could not. this value was associated with increased duration of icu stay and mv, and mortality. conclusion under acv, neither tdi, exdi nor tfdi were related to ptr,stim. under psv, tfdi was strongly correlated to diaphragm strength and, when decreased, was associated with poorer outcome. alexandre demoule has signed research contracts with covidien, maquet and philips; he has also received personal fees from covidien and msd. none. none. none. management of enteral feeding during extubation in the intensive care unit: a multi-center retrospective study in french intensive care units mickael landais , noemie hubert , mai-anh nay , johann auchabie , bruno giraudeau , reignier jean , arnaud w thille , stephan ehrmann none. none. nutritional support in patients receiving temporary extracorporeal life support: a retrospective cohort study arthur bailly , laurent brisard , philippe bizouarn , thierry lepoivre , johanna nicolet , jean christophe rigal , jean christian roussel , bertrand rozec réanimation ctcv transplantation thoracique, chu de nantes -hôpital nord laennec, saint-herblain, france; chirurgie ctcv transplantation thoracique, chu de nantes -hôpital nord laennec, saint-herblain, france correspondence: laurent brisard -laurent.brisard@chu-nantes.fr annals of intensive care , (suppl ):s introduction the optimal nutritional intake in patients receiving temporary extracorporeal life support (ecls), including extracorporeal membrane oxygenation (ecmo) venovenous (vv) or venoarterial (va), remains controversial. enteral nutrition (en) is suspect to increase risk of gastrointestinal (gi) intolerance and intestinal ischemia. so, total parenteral nutrition (tpn) is often preferred. the purpose of this study is to describe the nutrition practices for critically ill patients receiving ecls and identify opportunities for improving nutrition therapy in this population. patients and methods retrospective analysis of patients requiring ecmo-va or ecmo-vv between and in the cardiac surgery intensive care unit of the university hospital of nantes. nutritional support was daily monitored with parenteral intake (glucose, lipid and propofol, protein and albumin, parenteral nutrition) and enteral nutrition until ecls weaning. two groups were compared during ecls period: no enteral nutrition delivered (none or tpn) (anec, n = ) and at least once enteral nutrition delivered (nec, n = ) including en alone and supplemental parenteral nutrition (spn). primary outcome was incidence of gi intolerance and risk factors. secondary outcomes were nutritional adequacy (calculated as overall of calories and protein delivered divided by the theoretical amount requirements: kcal/kg/d and . g/kg/d) and clinical outcome. data are reported as median ( th and th percentiles) or number (%), and analyzed with student's t test for continuous variables and χ test for categorical variables. p < . was considered as significant. none.introduction refeeding syndrome (rs) is a potentially lethal condition that remains underdiagnosed. it is characterized by severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished patients undergoing refeeding orally, enterally, or parenterally. clinical criteria have been proposed for determination of its risk and reported in the national institute for clinical excellence (nice) clinical guidelines. hypophosphoremia (hp) is a prominent feature of the rs and seems to be the earliest abnormality. phosphorus is a vital component of nucleic acids, enzyme systems, and various metabolic pathways. objective to determine the incidence of refeeding hypophosphoremia (rh) < . mmol/l, and severe rh < . mmol/l in a medical critical care unit. patients and methods monocentric, retrospective and observational study with patients from french-speaking icu nutritional survey study frans. critically ill adults (more than yo) were enrolled if they were hospitalized for more than days during a -month period and had an artificial nutritional support. refeeding hypophosphoremia is defined by the occurrence of hypophosphoremia after refeeding. we studied the incidence of hr, risk factors, and prognosis. results patients were enrolled between / / and / / . rh appears in . % and severe rh < . mmol/l in . % (fig. ) . there is no correlation between rs risk factors and rh in our study. logistic regression did not permit to identify neither risk factor nor prognostic modification. there is a lack in phosphoremia measuring ( . %), and overfeeding during the first days occurs in . %. discussion we define that an hypophosphoremia appearing after refeeding is a refeeding hypophosphoremia, and we do not consider others etiologies, such as mechanical ventilation, alkalosis, sepsis, alcoholism, malabsorptive states, poor intake, some medication. our cohort is too small to find some possible correlations with risk factors or prognosis. conclusion refeeding hypophosphoremia is common in our population. hypophosphoremia is not an independent predictor of icu or in-hospital mortality in critically ill patients. the knowledge of the sri requires the follow-up of the phosphoremia during nutrition after critical illness in particular in the undernourished patients. none. introduction to determine the possible relationship between days cumulated proteins ( days cpd) and energy deficits ( days ced) observed in ventilated patients and icu length of stay, duration of ventilator support, incidence of infections and days mortality. patients and methods mixed medical or surgical ventilated for at least days adult patients from icus from chu liège belgium were enrolled into the study. they were fed by enteral route with a target of kcal and . g of proteins by corrected kg of bodyweight and by day. if % of the target was not reached on day seven, parenteral nutrition was added with the same target. ced and cpd were calculated for days, taking into account all the sources of nutrition, and was defined as the difference between the amount of energy or protein intake and the target. results from / / till / / , patients were followed. data from patients could be cumulated on the first days. there were males, mean bmi was . ± . ; saps ii score on day was . ± . , sofa score at day was . ± . . they were ventilated for a median of days (iqr - ), median icu length of stay was days (iqr - ). mean sofa max calculated for the first days was . ± . and the day mortality was . %. on day , only % reached the target of kcal/kg and % the target of . g of protein/kg. mean days ced was − . ± . kcal and mean days cpd was − . ± . g. there was a significant negative relationship between both deficits and the sofa max (p = . for ced and p = . for cpd). however, there were no correlations between any of the deficits and icu length of stay, duration of mechanical ventilation, occurrence of infections and days mortality. discussion saps ii level, sofa max level, icu length of stay, all these parameters emphasize the high severity of this cohort of patients. it could indeed been thought that it is in this group of critically ill patients that the impact of nutrition could be easily demonstrated. clear relationships between sofamax on day and the days ced and cpd could be seen. however, both the deficit and the level of organ dysfunctions could be cause or consequence. unlike previous studies, usually performed in less severely ill patients, we did not find any relationship between ced or cpd and patient's outcome. conclusion contrary to some recent studies, we found no relationship between ced and cpe and outcome of patients. future studies are needed. none. cardiopulmonary bypass induces lymphopenia and decreases lymphocyte proliferation ability: il- and pd-l as potential therapeutic targets to reduce postoperative infection fabrice uhel , mathieu lesouhaitier , murielle grégoire , baptiste gaudriot , arnaud gacouin , yves le tulzo , erwan flecher , karin tarte , jean-marc tadié fig. incidence of hypophosphoremia at admission, the first day, and refeeding hypophosphoremia none. the prognostic impact of neutropenia in criticallyill cancer patients remains controversial. hence, several studies in critically ill cancer patients failed to demonstrate the impact of neutropenia on outcome [ ] . this lack of statistical association might however, reflect a lack of statistical power. a previous meta-analysis of aggregated data suggested % ( % ci - %) raw increase in mortality in neutropenic patients. the available data were, however insufficient to allow adjustment with confounders [ ] . the aim of this study was to assess the influence of neutropenia on mortality of critically ill cancer patients using individual data obtained from studies identified by our systematic review. secondary objectives were to assess the influence of neutropenia on mortality of critically ill patients while taking into account underlying malignancy, use of g-csf or changes related to period of admission. patients and methods this systematic review and meta-analysis was performed according to the prisma statements. public-domain databases including pubmed and the cochrane database were searched by using predefined keywords. the research was restricted to articles published in english and studies focusing on critically ill adult patients from may to may . the methods and objectives of this systematic review were reported in the prospero database (crd ). selected manuscripts' authors were then contacted to obtained part of their dataset. mortality was defined as either hospital or day- mortality. this preliminary analysis reports results from the whole dataset before and after adjustment using logistic regression. period of admission and use of g-csf were then assessed and were a pre-planned analysis. results our initial search yielded citations and studies were retained for further analysis. overall, studies were excluded for redundancy with other included studies, as containing only neutropenic patients, and two as containing only palliative patients. finally datasets ( %) containing sufficient data to allow comparison were obtained from authors. overall, patients were included in this study, including patients with neutropenia at icu admission. median age was of years (iqr - ). median sapsii score at icu admission was (iqr - ). respectively and patients had underlying haematological malignancy and solid tumours, and patients underwent allogeneic stem cell transplantation. mechanical ventilation, vasopressors, and renal replacement therapy were required in none. none. ( ) . in icus, cirrhotic patients are widely admitted and revalued after receiving optimal treatments for days. however, little is known about how manage these patients after day according to their prognosis. the blood neutrophil-to-lymphocyte ratio (nlr) as a novel inflammation index biomarker has been reported to be a predictor of clinical outcomes in various malignancies and in unselected critically ill patients ( ) . nlr has also been identified as a predictor of mortality in patients with stable liver cirrhosis. to our knowledge, the ability of nlr to predict outcome in critically ill cirrhotic patients has never been studied. the aim of this study was to evaluate the usefulness of inflammatory marker such as nlr for diagnosis of infection and predicting the outcome in hospitalized critically ill cirrhotic patients. we performed a retrospective monocentric study including consecutively cirrhotic patients hospitalized in a medical icu from to . for each patient, clinical and biological data at admission and day were collected. nlr at admission ("nlrd "), at day ("nlrd ") and the variation of nlr between admission and d none.introduction diagnosis of infection in immunocompromised patients can be difficult. however, diagnosing infection is very important, particularly in critically ill. this study aims to evaluate the benefit of procalcitonin (pct) blood level as a diagnostic marker for bacterial infection in patients with hematological malignancies admitted to the intensive care unit (icu). this retrospective single-center study included all consecutive patients with acute myeloid leukemia or high grade lymphoid malignancy admitted to the icu. patients were sorted into three subgroups, according to clinical and microbiological data: «infectious disease», «no infectious disease» and «unknown». initial serum pct and when available at day and day were recorded. receiver operating characteristic (roc) curve, sensitivity and specificity were calculated. serum pct was considered as decreasing when the decrease was ≥ % at day and/or ≥ % at day . mortality rates in the icu and at day- were also studied. results fifty-four patients were included in the study. at diagnosis, pct levels were significantly different between the "infection disease" group and the "no infection disease" group (p = . ). there was no difference between the "infection disease" group and the "unknown" group (p = . ). for the diagnosis of bacterial infection, best initial serum pct threshold was . ng per milliliter. for that threshold, sensitivity was . % and specificity was . %. pct area under the roc curve was . [ci % = . - ]. youden's j statistic was . . pct levels weren't different between groups according to the presence of neutropenia or in case of inaugural disease. there was a significant difference in pct values between groups according to the sofa score (p = . ), but not the saps score. mortality rate in the icu and at day- were significantly lower for the patients with decreasing pct (p < . and p < . , respectively). when comparing serum pct and crp predictive values, pct was significantly a better marker of bacterial infection (fig. ). discussion we found that serum pct, with a threshold of . ng/ ml, is a reliable marker of bacterial infection disease in patients with aggressive hematological malignancy admitted to the icu. our study confirms the results of a previous study in unselected immunocompromised patients admitted to the icu, showing a % sensitivity, a % specificity and an area under roc curve of . [ . - . ] for a threshold of . ng/ml ( ). the main limitations of our study are its retrospective design and the small number of included patients. conclusion pct is a reliable marker of bacterial infection in patients with hematological malignancies admitted to the icu. pct kinetic seems to be an interesting prognostic marker in this population. none. in this study, we have found that kinetics of secretion and expression of endocan is faster with huvecs stimlated by tlr agonist than tlr agonist. this results could suggest that endocan may be not only a marker of septic shock but could be also a specific marker to recognize the nature of pathogenic microorganisms in septic shock. furthermore, other studies with more tlr agonists could be useful to confirm these results. conclusion studying the effects of diverse tlrs agonists could make the plasmatic dosage of endocan more specific and helpful to recognize the nature of pathogenic microorganisms in septic shock. none. lung ultrasound: help to the diagnostic and the monitoring of response to physiotherapy. a case report of pneumonia aymeric le neindre introduction chronic critical illness (cci) syndrome is a new condition affecting an increasing number of patients, who survived an acute critical illness but have persistent severe organ dysfunction, requiring prolonged specialized care. cci is a iatrogenic process, reflecting the efficacy of modern life support technologies( ), and encompasses multiple organ failure, need for prolonged mechanical ventilation (mv), organ support, and palsy due to polineuromyopathy. the transition from acute to cci is gradual: definitions are based on duration of mv, with cut-offs of , or consecutive days of mv for ≥ h/day. cci patients may come from either medical or surgical icu; their health status fluctuates between improvements and deteriorations implying recurrent transitions between different levels of care ( ) .the risk of death is reported to be as high as %. despite a relatively young age ( years on average), functional status of cci patients discharged is seriously impaired, thus cci patients require long-term rehabilitation. aim: to estimate the frequency of cci syndrome in careggi, a large academic, tertiary care hospital; to describe the clinical course of cci patients through discharge, and their functional status at discharge. patients and methods administrative data on admission, transfer, death and discharge of all cci patients, consecutively admitted in one of the icu beds at careggi hospital from january to december , , were collected. cci was defined with the cut off of ≥ days of icu stay, representing the index event (ie) without contribution of previous or subsequent hospitalization in other hospitals. reasons for admission were grouped into the broad categories of medical causes, surgery, major trauma and cardio-respiratory arrest. patients discharged were evaluated in daily living, cognitive status, and mobility using barthel index. results we identified subjects who developed cci ( males; age . ± . years, mean ± sem); of them came from an external icu, began their cci course within careggi hospital ( from the emergency room, from a regular ward). average duration of the ie was . ± . days. these sample developed accumulative length of icu stay of days, corresponding to a % icu bed occupation over the theoretical total of , . when days of subintensive care and regular ward were separately added, days of highly specialized care and days of total acute hospital stay were reached. surgical patients had longer hospitalizations (p = . ).cci patients confirmed to be highly erratic: a total of transitions across different services were recorded in the patients, with a maximum of in of them. mean age was comparable between the patients who died ( %) and the remaining who were discharged alive ( . ± . vs. . ± . years; p = . ).fourteen subjects continued their icu stay out of hospital. only , whose age was lower ( . ± . years), were discharged home; half of the participants (n = , . %) were admitted to a residential rehabilitation facility. younger subjects scored better in the domains of self care (p = . ) and cognitive status (p = . ) but not in the domain of mobility, including walking ability: patients required maximal assistance in performing activities of daily living and transfers, other required medium/maximal assistance, with no statistical difference between dg group. conclusion cci is a relevant clinical condition that need to be assessed and possibly prevented, as it causes severe morbidity, long-term functional impairment and exceeding healthcare costs. none.conclusion early mobilization during the first week of the sepsis onset was safe and preserved muscle fibre cross sectional area. none. none. study of efficacy on icu acquired weakness of early standing with the assistance of a tilt table in critically ill patients none.introduction patients with high flow nasal cannula may benefit from combined aerosol therapy. clinical efficacy depends on pulmonary deposition which is related to the type of nebulizer. all new nebulizers or delivery methods require rigorous evaluation. the aim of this study was to compare lung deposition between two nebulizers (jet nebulizer vs vibrating-mesh nebulizer) through high flow nasal cannula in healthy subjects. patients and methods aerosol delivery of diethylenetriaminepentaacetic acid labelled with technetium- m ( mtc-dtpa, mci/ ml) to the lungs using a vibrating-mesh nebulizer (aerogen solo ® , aerogen ltd., galway, ireland) and a constant-output jet nebulizer (opti-mist plus nebulizer ® , convatec, bridgewater, nj) through high flow nasal cannula (optiflow ® , fisher & paykel, new zealand) was compared in healthy subjects. flow rate was set at l/min through the heated humidified circuit. pulmonary and extrapulmonary deposition were measured by single photon emission computed tomography combined with a low dose ct-scan (spect-ct) and by planar scintigraphy. results lung deposition was only . ± . and . ± . % of the nominal dose with the vibrating-mesh nebulizer and the jet nebulizer, respectively (p < . ). dose lost in the high flow circuit, humidification chamber and nasal cannula was higher with the vibrating-mesh nebulizer as compared to the jet nebulizer ( . ± . vs . ± . % of the nominal dose, p = . ). expressed as percentage of emitted dose, lung deposition was similar with both nebulizers. conclusion this study demonstrated that aerosol delivery through hfnc is poor in the specific conditions of the study despite the higher efficiency of the vibrating-mesh nebulizer as compared to the jet nebulizer. placing the nebulizer on the hfnc circuit at l/min induces high aerosol loss on the circuit and the oropharynx. key: cord- -xilbhy authors: gattinoni, luciano; marini, john j.; chiumello, davide; busana, mattia; camporota, luigi title: covid- : scientific reasoning, pragmatism and emotional bias date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: xilbhy nan we thank dr. tobin et al. for their comments [ ] in response to our letter [ ] . at this time of uncertainty, clinicians turn to experts and opinion leaders for advice on how to best manage a patient afflicted by a new and complex disease which affects primarily-but not exclusively-the respiratory system. under the strains of pandemic practice, everyone is trying hard; clinicians must strike a sensitive and difficult balance in managing a relentless caseload with the limited (if not inadequate) resources at their disposal. in the midst of early applause by the general public and intense scrutiny by healthcare systems and governments-it is clear that there has been wide variability in the provision of care for patients of similar severity affected by covid- . when all answers are in, is quite possible that some of the initial applause will turn eventually into fault-finding and condemnation. in this context, it is very well to "sit on the fence" and from there launch darts of judgment at those who are trying to express a particular view, as long as these contestations help clinicians in their decision-making. yet, it seems to us that most of the arguments, counterarguments, attempts to correct, disparage and set-therecord-straight expressed by tobin et al. [ ] are aimed, not so much at the worth or fault of the arguments per se, but at their proponents-namely, us. this impression stems from the observation that among the avalanche of articles published since january , which contain a wide spectrum of opinions (as should be expected when the evidence is patchy and apparently inconsistent), none beside our own have received such an exacting response. leaving aside these reflections, other considerations need to be brought to the fore: the quibbling and partial nature of the objections raised. when trying to piece together the pathophysiology of this unfamiliar entity, to this point we have had to rely on fragmentary evidence, logic and scientific intuition. it is not difficult to imagine that to the ideas and examples we report in our manuscripts, dr tobin-or anyone else-will be able to find exceptions and contradicting evidence. the scientific literature is full of such examples. anyone can do the same-if they simply wish to abrogate a point of view. all intensivists know with certainty that invasive mechanical ventilation may be life-saving. no one proposes otherwise. yet, we should not be criticized when we suggest that tobin and co-authors had expressed views that premature intubation in this covid context is "fatal". for example, recently in the american journal of respiratory and critical care medicine, we can find: "the surest way to increase covid- mortality is the liberal use of intubation and mechanical ventilation" [ ] . clearly, the meaning and interpretation of the word "liberal" in this context is wide-ranging. however, the contention that mechanical ventilation is "the surest way to increase covid- mortality" -is not supported by clinical data and therefore, once again such a statement is yet to be proved or disproved. our detractors failed to note that we had focused our recommendations for early intervention on those patients who continue (or intensify) vigorously labored breathing with less invasive therapy. another example is provided when tobin et al. say "patients with acute severe asthma develop large pleural open access *correspondence: gattinoniluciano@gmail.com department of anesthesiology, emergency and intensive care medicine, university of göttingen, göttingen, germany full list of author information is available at the end of the article pressure swings, yet autopsy studies in patients dying because of status asthmaticus are remarkable for the absence of pulmonary edema" [ ] . it is unfortunate that in the study quoted, the main histological characteristics-as the title of that paper suggests, "… reference to changes in the bronchial mucosa" [ ] . indeed, almost decades later another uncited paper from a prominent journal reported edematous lungs in children with severe asthma [ ] . it seems, therefore, that the strong breathing efforts of asthma as well as those during upper airways obstruction promote "negative pressure pulmonary oedema". similar hydrostatic forces are at work during labored breathing in the fluid-permeable lungs of covid- . we agree that at present, worsening of a chest x-ray cannot be linked directly to p-sili [ ] ; however, results of the recently published study by tonelli [ ] is mechanistically consistent with the hypothesis we have been trying to advance [ ] . the tidal volumes and pressures during niv are too variable and too influenced by the integrity of the interface seal to definitively support or disprove p-sili. ethics dictate that there can be no 'experimentum crucis' of deliberate iatrogenic injury, as seems to be requested from us by our critics. we do not wish to maintain ongoing arguments with tobin et al. [ ] -who we respect as clinicians and scientists who have greatly contributed to the advancement of critical care. nonetheless, readers do need to objectively consider the merit of such arguments and our response to them. by doing so, hopefully they may reconcile those that square best with their own clinical experience until these important management issues are definitively resolved. surely, we are entitled to put forward a hypothesis to the scientific community without meeting the same unremitting finger wagging response in a time of uncertainty that demands that we choose the most logical approach to clinical problems we cannot ignore. we are left with the same conclusion: to prove and disprove something is the basis of scientific progress. it is possible, then, that future data will disprove the non-existence of spontaneously induced lung injury or prove the tragic consequences of ignoring it. p-sili is not justification for intubation of covid- patients spontaneous breathing, transpulmonary pressure and mathematical trickery basing respiratory management of covid- on physiological principles the pathology of asthma, with special reference to changes in the bronchial mucosa mechanical forces producing pulmonary edema in acute asthma early inspiratory effort assessment by esophageal manometry predicts noninvasive ventilation outcome in de novo respiratory failure. a pilot study publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. all authors contributed equally to the drafting of the manuscript and provided critical revision for important intellectual content. all authors read and approved the final manuscript. none. not applicable.ethics approval and consent to participate not applicable. not applicable. none. key: cord- - lx fkv authors: bagate, françois; tuffet, samuel; masi, paul; perier, françois; razazi, keyvan; de prost, nicolas; carteaux, guillaume; payen, didier; mekontso dessap, armand title: rescue therapy with inhaled nitric oxide and almitrine in covid- patients with severe acute respiratory distress syndrome date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: lx fkv background: in covid- patients with severe acute respiratory distress syndrome (ards), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for va/q mismatch, as hypoxic vasoconstriction alteration. this study aimed to evaluate the capacity of inhaled nitric oxide (ino)–almitrine combination to restore oxygenation in severe covid- ards (c-ards) patients. methods: we conducted a monocentric preliminary pilot study in intubated patients with severe c-ards. respiratory mechanics was assessed after a prone session. then, patients received ino ( ppm) alone and in association with almitrine ( μg/kg/min) during min in each step. echocardiographic and blood gases measurements were performed at baseline, during ino alone, and ino–almitrine combination. the primary endpoint was the variation of oxygenation (pao( )/fio( ) ratio). results: ten severe c-ards patients were assessed ( males and females), with a median age of [ – ] years. combination of ino and almitrine outperformed ino alone for oxygenation improvement. the median of pao( )/fio( ) ratio varied from [ – ] mmhg at baseline, to [ – ] mmhg after ino (p = . ) and [ – ] mmhg after ino and almitrine (p < . ). we found no correlation between the increase in oxygenation caused by ino–almitrine combination and that caused by proning. conclusion: in this pilot study of severe c-ards patients, ino–almitrine combination was associated with rapid and significant improvement of oxygenation. these findings highlight the role of pulmonary vascular function in covid- pathophysiology. severe acute respiratory syndrome coronavirus (sars-cov- ) which is responsible for the coronavirus disease (covid- ) pandemic is causing a massive influx of patients presenting with severe acute respiratory distress syndrome (ards) to intensive care units (icus) worldwide [ ] . for the most severe cases, refractory ards may lead to a discussion regarding the use of extracorporeal membrane oxygenation (ecmo), an expensive and invasive life support resource, available in limited numbers in expert centers [ , ] . since the possibilities cannot fit with the large-scale outbreaks, alternative solutions should be proposed [ ] . some authors have hypothesized that potential relatively preserved respiratory system compliance (crs) despite severe hypoxemia in covid- patients suggests a possible hemodynamic mechanism for ventilation/perfusion (va/q) mismatch as hypoxic vasoconstriction alteration [ ] . the sars-cov- uses angiotensin converting enzyme (ace ) receptor expressed by pneumocytes in the epithelial alveolar lining to infect the host, thereby causing lung injury, but the ace receptor is also widely expressed on endothelial cells, including the heart, kidney, intestine and lung. the presence of viral elements within endothelial cells with an accumulation of inflammatory cells, suggest that sars-cov- infection may induce endotheliitis altering vascular reactivity [ ] including the hypoxic vasoconstriction or other vasomotion control. the combination of inhaled nitric oxide (ino), a selective pulmonary vasodilator, and almitrine, a specific pulmonary vasoconstrictor, was proposed several decades ago as to improve va/q mismatch. it was spectacular in many ards patients with maintained vasodilation in ventilated zones receiving ino and reduced perfusion in poorly or non-ventilated zones after almitrine treatment [ ] [ ] [ ] . in the particular context of covid- , we hypothesized that ino-almitrine combination could improve arterial oxygenation in severe covid- ards (c-ards) by a redistribution of the pulmonary blood flow towards ventilated areas. intubated patients with laboratory-confirmed covid- , who met the criteria for ards (berlin definition) [ ] with persistent severe hypoxemia (pao / fio < mmhg), were prospectively included at the medical icu of henri mondor university hospital (creteil, france). sars-cov- infection was confirmed by real-time reverse transcriptase-polymerase chain reaction (rt-pcr) assay of nasal swabs or lower respiratory tract samples (bronchoalveolar lavage or endotracheal aspirate). age lower than years, acute cor pulmonale defined as septal dyskinesia with dilated right ventricle (end-diastolic right ventricle/left ventricle area ratio > . ), pulmonary embolism, hyperlactatemia (> mmol/l), hepatic insufficiency, and ecmo support were exclusion criteria. respiratory settings and ards management were in accordance with french guidelines [ ] . the study was approved by the ethics committee of the french intensive care society as a component of standard care, and patient consent was waived as per french law. families were given information about the study. enrolled patients were sedated and received neuromuscular blockers to maintain a volume-control mechanical ventilation adapted to keep the tidal volume around ml/kg of predicted body weight (pbw) and the paco below mmhg. after hemodynamic and ventilatory optimization, prone positioning was tested because of persisting severe hypoxemia (pao /fio < mmhg). after a proning session lasting to h, the patients were put back to supine position and the ino ( ppm) alone followed by ino associated with mcg/kg/min of almitrine (vectarion ® , servier, suresnes, france) were tested. the fio was settled at to limit heterogeneity within patients and to look at the effect of the drugs on true qs/qt, eliminating mostly the low va/q zones. the effect on arterial oxygenation was evaluated at least after min in each condition: supine baseline, ino, and ino plus almitrine. because of the potential negative impact of right ventricle afterload increase during almitrine, the right ventricular function was assessed by echocardiography along with arterial blood gases at baseline, during ino alone, and with ino-almitrine combination. patients who had a pao /fio ratio that increased by at least % or by mmhg as compared to the baseline situation were considered "responders" [ ] . the assessment of respiratory mechanics included the following measurements. plateau pressure and total peep were assessed during an end-inspiratory ( . s) and end-expiratory ( - s) occlusion maneuver, respectively. the driving pressure and the crs were computed as the difference between plateau pressure and total peep and tidal volume divided by the difference between plateau pressure and total peep, respectively. the potential airway closure phenomenon was detected by measuring the airway opening pressure during a low flow (≤ l/ min) insufflation and potential for lung recruitment was assessed by the mean of the recruitment-to-inflation ratio (r/i ratio) computation, as previously described by chen et al. [ ] . a r/i ratio < . was used to characterize a poorly recruitable patient. trained operators (competence in advanced critical care echocardiography) performed transthoracic echocardiography in the supine position at baseline, and during ino and almitrine administration. they focused on global function (velocity-time integral of left ventricular outflow tract, cardiac index), and the right ventricle function as previously proposed [ ] . because of severe hypoxia, all patients had a detection of potential shunting across patent foramen ovale in four-chamber view after injection of sterile-modified fluid gelatine solution (plasmion, fresenius-kabi, sevres, france) aerated with room air to generate microbubbles as previously proposed [ ] . the following data were collected at inclusion: age, gender, body mass index, past medical history, standard treatments, charlson comorbidity index, sequential organ failure assessment (sofa) score [ ] , simplified acute physiologic score (saps) ii [ ] , and the need for vasopressors. in addition, the need for ecmo support, limitation of life-sustaining therapies and icu mortality were collected during hospitalization. statistical analyses were performed with the jmp software (version ; sas institute inc, cary, nc) and graph-pad prism software (version ; graphpad software inc., la jolla, ca, usa). the primary endpoint of this study was the variation of oxygenation (pao /fio ). data were presented as median with interquartile range or number with percentage. multiple paired values were compared using friedman test followed by paired wilcoxon test with benjamini-hochberg correction. spearman's test was used to assess correlation. for all tests, a two-way p-value < . was considered statistically significant. as a pilot study, ten severe c-ards patients were assessed (seven males and three females), with a median age of [ - ] years. median time since endotracheal intubation was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days, allowing to mix potential different hypoxic mechanisms. clinical characteristics, comorbidities, standard treatments and organ failures at inclusion are presented in table . as shown in additional file : table s , the gas exchange response of the last prone position the day before the protocol was favorable (increase in pao /fio of at least % or mmhg) in most ( / , %) patients; overall, the pao /fio ratio increased from [ - ] mmhg (supine) to [ - ] (prone), p < . (additional file : table s ). respiratory mechanics in supine position after proning are reported in additional file : table s . the median values of crs and driving pressure were [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ml/cmh o, and [ ] [ ] [ ] [ ] [ ] mmhg, respectively. r/i ratio was < . in / ( %) patients, indicating limited recruitability in a majority of patients. in supine position, patients were still severely hypoxic with median pao of [ - ] mmhg at fio of ( table ) . on supine position, only the addition of almitrine to ino increased significantly pao from baseline ( fig. ) , with no significant changes in pulmonary blood flow and other hemodynamic and echocardiographic variables ( table ). pao increased by more than % in seven of ten patients with ino-almitrine combination (additional file : figure s ). one non-responder had an intra-cardiac shunt related to patent foramen ovale. the response to ino + almitrine did not correlate with the benefit on pao induced by prone positioning (ρ = − . , p = . ). similarly, the baseline respiratory mechanics were not associated with the ino-almitrine response (additional file : table s ). although the study was not designed to evaluate the impact on outcome, it is important to report that six out of ten patients had a refractory hypoxemia (pao / fio < mmhg), which could not be treated by almitrine due to the shortage of drug reserve. one patient benefited from ecmo support with a favorable final outcome, the five remaining could not be treated by ecmo and died during icu stay. the main findings of this pilot study were as follows: i) only the combination of ino and almitrine improved the arterial oxygenation in severe c-ards patients; ii) in vitro studies suggested a direct antiviral effect of ino on the sars-cov replication cycle [ , ] . during the first sars-cov outbreak in , a pilot study reported the efficacy of ino in a limited series of severe patients, with reversal of pulmonary hypertension, improved hypoxemia and shortened duration of mechanical ventilation [ ] . some authors suggested that ino could be used as a rescue therapy during the current pandemics [ , ] , inasmuch as covid- is characterized by major pulmonary vascular dysfunction with endothelialitis, and thrombosis [ , ] . in our case series, ino alone had a negligible effect on oxygenation. in addition, in the absence of rv dysfunction, ino did not change the rv d echocardiographic measures. these results confirm the adequate exclusion of patients with pulmonary hypertension and/or rv dysfunction, to safely use almitrine. ongoing randomized controlled trial testing ino will probably shed light on its usefulness in a broader population of patients with c-ards [ ] . some authors have hypothesized that in some patients with c-ards (especially those with low elastance-"l type"), hypoxemia was not completely explained by pulmonary shunt resulting from diffuse alveolar damage [ ] . the respiratory mechanics of our selected patients did not fully match with the proposed "l type", described by gattinoni et al. [ ] , but was in accordance with a recent larger cohort of critically ill adults with covid- [ ] . the frequency of vascular and perfusion abnormalities [ ] and pulmonary embolism incidence seems higher in covid- pneumonia as compared to classical ards [ ] . there is also a specific pulmonary procoagulant pattern [ ] , causing alveolar capillary microthrombi, as revealed by post-mortem studies [ , ] . more interestingly, ackermann et al. reported [ ] the presence of intussusceptive angiogenesis. these anomalies may alter hypoxic pulmonary vasoconstriction, a possible mechanism for va/q mismatch and hypoxemia during c-ards. addition of almitrine to ino in patients with c-ards has the potential for restoring vascular homeostasis, in particular hypoxic pulmonary vasoconstriction [ ] . the first reported study on almitrine in severe hypoxia in covid- patients [ ] showed a highly significant increase in p/f ratio with almitrine, independently from the dose used ( or mcg/kg/min). because the level of pvo entering the pulmonary circulation is a major controller of hypoxic pulmonary vasoconstriction [ ] , they measured the svo , that increased significantly. recently, barthélémy et al. [ ] described the effect of almitrine in critically ill covid- patients. in this study, almitrine ( μg/kg/min) globally increased oxygenation within h of infusion start. however, the studied population was heterogeneous, and the effect of prone position was not reported. another study reported the effect of ino ( to ppm in patients), almitrine ( . mg/ kg over min in patients), or both ( patients). surprisingly, the authors failed to observe any oxygenation improvement, with all patients investigated in prone position [ ] . taken together, previous reports and our study suggest a beneficial effect mainly during almitrine infusion in c-ards in the supine position. in our study, since pulmonary blood did not change, it is reasonable to consider that the drugs combination creates pulmonary resistance gradient favoring the perfusion of ventilated areas reducing the va/q mismatch [ ] . these data are consistent with previous larger studies in non-covid ards [ , , ] . moreover, a recent preliminary study in non-covid ards patients with veno-venous ecmo support, might renew the interest for almitrine [ ] . the role of ino and almitrine in the therapeutic arsenal of ards is not yet completely clear, but it is reasonable to consider ino and almitrine as potential rescue therapies that might be applied in case of persisting severe hypoxemia despite prone positioning and before considering ecmo [ ] . our study suffers from several limitations. first, it is a pilot study on a small cohort, with no control group of ards not resulting from covid- , making the results only exploratory. however, our c-ards patients were homogeneous in terms of severity and selection. second, because of limited drug availability, we did not evaluate the prolonged effect of this therapeutic combination. thus, full interpretation on efficacy and tolerance is not possible. we did not observe adverse events on this short duration of administration. at least for a short duration, almitrine did not cause hyperlactatemia, hemodynamic instability (by favoring acute cor pulmonale), or hepatic disturbances [ ] . third, we could not standardize the timing of evaluation referring to prone position. a potential impact of additive effects of prone position and ino-almitrine on arterial oxygenation cannot be ruled out [ ] . fourth, ventilation in fio may theoretically increase the alveolar partial pressure in oxygen and inhibit or at least decrease hypoxic pulmonary vasoconstriction in non-or hypo-ventilated areas. however, an fio of was used for the following reasons: i) the level of hypoxia for almost all patients necessitated very high fio close to ; ii) the fio of allows measuring hypoxia mainly related to true qs/qt and not low va/q zones. it is then more rigorous to compare the results of modification of true shunt instead of global venous admixture containing also low va/q; iii) the gas equation used to calculate the p/f ratio may introduce large bias as previously shown. in this small series of severe c-ards patients, the ino-almitrine combination was associated with rapid and significant improvement of oxygenation, which was not observed with ino alone. these findings highlight the role of pulmonary vascular vasoreactivity in covid- , which could partially be corrected by almitrine. this may help to avoid the ecmo or delay the time at which ecmo can be initiated. this aspect could only be evaluated in a randomized clinical trial in presence or not of almitrine. more work is warranted to test whether the prolonged use of these medicines could alter the long-term outcome of such patients. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file : table s . blood gas before and after the last proning session in ten patients with severe acute respiratory distress syndrome secondary to coronavirus disease . additional file : figure s . individual values of the ratio of oxygen partial pressure to inspired oxygen fraction in arterial blood in patients with severe acute respiratory distress syndrome secondary to coronavirus disease , according to position (prone or supine) and administration of inhaled nitric oxide with or without almitrine. * , # and & denote a p value < . for paired wilcoxon (with benjamini-hochberg correction) following friedman test, as compared to supine (before prone), supine (after prone), and supine with ino, respectively. red lines: "almitrine non-responders"; blue lines: "almitrine responders"; solid lines: "prone responders"; dashed lines: "prone non-responders". additional file : table s . respiratory mechanics in supine position in ten patients with severe acute respiratory distress syndrome secondary to coronavirus disease . table s . correlations between respiratory mechanics and oxygenation response to the combination of inhaled nitric oxide and almitrine in ten patients with severe acute respiratory distress syndrome secondary to coronavirus disease . a novel coronavirus 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hypoxemia inhaled no and almitrine bismesylate in patients with acute respiratory distress syndrome: effect of noradrenalin evaluation of almitrine infusion during veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults intravenous almitrine bismesylate reversibly induces lactic acidosis and hepatic dysfunction in patients with acute lung injury publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we are very indebted to all physicians and nurses of the henri mondor medical intensive care unit for their help for the care of covid- patients. authors' contributions fb, st and amd designed the study and wrote the manuscript. fb, pm and fp collected the data. kr, ndp, gc and dp designed the study. all authors read and approved the final manuscript. the present study has been conducted without any financial support. all data generated and analyzed during the study are included in the published article and can be shared upon request. all authors helped to revise the draft of the manuscript. all authors read and approved the final manuscript. the study was approved by the institutional ethics committee of the french intensive care society as a component of standard care and patient consent was waived as per french law. information about the study was given to families. not applicable. the authors declare that they have no competing interests.author details ap-hp, hôpitaux universitaires henri-mondor, service de médecine intensive key: cord- -jj anf g authors: shang, you; pan, chun; yang, xianghong; zhong, ming; shang, xiuling; wu, zhixiong; yu, zhui; zhang, wei; zhong, qiang; zheng, xia; sang, ling; jiang, li; zhang, jiancheng; xiong, wei; liu, jiao; chen, dechang title: management of critically ill patients with covid- in icu: statement from front-line intensive care experts in wuhan, china date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: jj anf g background: the ongoing coronavirus disease (covid- ) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. statements from front-line experts in the field of intensive care are urgently needed. methods: sixteen front-line experts in china fighting against the covid- epidemic in wuhan were organized to develop an expert statement after rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill covid- patients. each expert was assigned tasks within their field of expertise to provide draft statements and rationale. parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences. results: a comprehensive document with statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill covid- patients. among them, recommendations were strong (grade ), were weak (grade ), and were experts’ opinions. a strong agreement from voting participants was obtained for all recommendations. conclusion: there are still no targeted therapies for covid- patients. dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important. the outbreak of novel coronavirus pneumonia that was first detected in wuhan in december resulted in a worldwide pandemic. on february , , the world health organization (who) formally named it coronavirus disease . a person with laboratory confirmation of virus causing covid- infection, irrespective of clinical signs and symptoms, is considered as a confirmed case [ ] . globally, more than , , confirmed individuals and over , deaths, across more than countries, territories or areas have been reported [ ] . approximately % of confirmed cases developed severe disease [ ] , while the grand fatality rate was . % [ ] . as the virus continues to spread at an alarming rate, healthcare workers are seeking effective and actionable management for affected patients. in china, physicians have been coping with covid- for over months. most of the people who contracted covid- presented with mild symptoms ( . %), then severe ( . %), and finally critical ( . %) ( table ) [ ] . most of the confirmed cases were between the ages of and ( . %), diagnosed in hubei ( . %), with the overall fatality rate of . %, and . % in health workers [ ] . the case fatality rate for critical cases was . % [ ] . patients with underlying diseases had much higher fatality rates than patients with no underlying diseases ( . % for cardiovascular disease, . % for diabetes, . % for chronic respiratory disease, . % for hypertension, . % for cancer, and . % for none) [ ] . the epidemic outbreak curve peaked around january - , , after which the decline ensued. a recent single-center study found that most critical patients developed organ dysfunction, where % were found to have acute respiratory distress syndrome (ards), % with acute kidney injury (aki), % with cardiac injury, % with liver dysfunction, and % with pneumothorax [ ] . besides these epidemiological findings, chinese experts have gained valuable experience in the management and pathology of this disease. we consider it our responsibility to share these experiences through the expert consensus. chinese specialists in critical care medicine were organized and worked together to develop an expert statement after five rounds of expert seminars and discussions. this statement represents a synthesis of evidence and experts' consensus on critical care, despite the lack of clinical trials. critical cases are characterized by exhibited respiratory failure, septic shock, and/ or multiple organ dysfunction/failure [ ] . in experts' opinion, the patients should also be considered as critical cases if they are suffering from high respiratory frequency (rr ≥ bpm) and low oxygen index (arterial partial pressure of oxygen (pao )/fraction of inspired oxygen (fio ) ≤ mmhg) under high-flow nasal cannula oxygen therapy (hfnc). the experts drew up sections on the management of covid- disease, mostly based on the experience in wuhan. the statements were drawn up by a group of front-line intensive care experts in china who fought against the covid- epidemic in wuhan. the group's agenda was predefined. the expert group first defined clinical questions to be addressed and then designated the experts in charge of each question after a first meeting. all the questions were formulated according to the population, intervention, control, and outcome (pico) format, which helps defining inclusion and exclusion criteria for the literature searches and identifying relevant studies. the quality of evidence was assessed using the methodology described in grades of recommendation, assessment, development, and evaluation (grade). the quality of evidence can be high, moderate, low, or very low. because of the sudden outbreak of a covid- , the proposed question could be the subject of a recommendation as an expert opinion due to inexistent or insufficient literature. in addition, the published data on severe acute respiratory syndrome (sars), middle east respiratory syndrome (mers) and other coronaviruses infections, as well as data on supportive care in the icu from studies on influenza and other respiratory viral infections, ards and sepsis was used as indirect evidence. a total of rounds of expert seminars and discussions were organized to provide trustworthy recommendation on the management of critically ill covid- patients (table ) . we use the wording "we recommend", "recommended", "should" or "should not" for strong recommendations, "should probably", "should probably not" or "should probably be considered" for weak recommendations, and "the experts suggest", "the experts suggest against", "suggested" or "not suggested" for expert opinion. the implications of the recommendation strength are presented in table . the proposed recommendations were discussed one by one. at least % of experts agree to approve a proposal for criteria, and at least % of experts must agree to reach a strong agreement. in the absence of strong agreement, choose to reformulate the proposal and re-rating, in order to reach consensus. only the expert opinions that give strong agreement are retained. the prevention and control of infections, diagnostic strategy, therapeutic management, and transportation of patients were defined. literatures were searched via pubmed and the cochrane library databases. only articles published in english or with an english abstract were included in the analysis focused on recent data according to an order of appraisal ranging from meta-analyses to randomized trials to observational research studies. the study population size and research relevance were considered for each study. according to the grade method and summary of the results, experts drew up statements. of these guidelines, had a high level of evidence (grade ±), had a low level of evidence (grade ±), and were expert opinions. a strong agreement was reached for all statements after two rounds of scoring. as the front-line of the covid- outbreak response, health care workers are exposed to a huge risk of infection. therefore, health care workers must follow the standard precautionary principles and try their best to ensure the personal protection, hand hygiene, ward management, environmental ventilation, and sanitization of the object surface, so as to avoid nosocomial cross-infection. statement implementation of standard precautions, strengthening ward management, and self-management are suggested safety measures for health care workers (expert opinion). rationale averted by the current epidemic situation of covid- , taking proper precautions is essential for avoiding the spread of infection among health care workers. thus, the following points need to be considered. as a high-risk environment, tertiary class protection is suggested for health care workers in intensive care unit (icu). personal protective equipment (ppe) includes disposable surgical cap, n mask, work uniform, disposable medical uniforms, disposable latex gloves, goggles, and full-face shields. full-face respiratory protective devices or powered air-purifying respirators are required when performing aerosol-generating procedures. destroying and disposing of masks properly, putting on and removing ppe, and practicing hand hygiene are necessary to avoid self-contamination. special attention should be paid to details such as the side exposure of the eyes and wrists with glove slippage, as well as the risks of infection while removing some disposable shoe covers [ ] . the hand hygiene system should be strictly implemented table statement timeline march , designating the experts in charge of each addressed question each expert made a detailed outline of their respective question march , discussing and resolving the problems encountered by the experts in the process of making the statements april , ( ) discussing the experts' respective statement and rational after revision; ( ) first round of scoring april , guideline finalization meeting for the second round of scoring table recommendations according to the grade methodology grade + strong recommendation "…we recommend…", "…recommended…" or "…should…" high level of evidence grade + weak recommendation "…should probably…" or "…should probably be considered…" low level of evidence expert opinion recommendation in the form of an expert opinion "…the experts suggest…", "…suggested…", "…the experts suggest against…", or "…not suggested…" [ ] . clinical triage system needs to be established to assess all patients at admission, allow for early recognition of possible covid- cases and immediate isolation of patients with suspected disease in an area separate from other patients (source control). the number of family members and visitors who are in contact with suspected or confirmed covid- patients should be limited or visiting should be prohibited altogether. the proper disposal of clinical waste should be ensured [ ] . health care workers need to self-monitor for signs of illness and self-isolate. if illness occurs, they should report it to managers and stay at home. a sensible diet, proper rest, and adequate exercise are advised to maintain physical and psychological health. health care workers should familiarize themselves with related working procedures so as to avoid mistakes [ ] . proper icu ward setting, necessary equipment and facilities, and strict icu environmental disinfection, are suggested (expert opinion). rationale it is suggested to adjust measures according to the differing conditions so as to set the icu ward rationally. contaminated areas, potentially contaminated area and clean areas need to be strictly divided. the buffer zone should be set between every two areas. posting eye-catching logos on each area is required to prevent straying into the wrong place. different points of access should be set for medical staff and patients, making sure they do not get crossed. for icu, tertiary class protection should be correctly performed in each area, which is of great importance for precaution of covid- [ ] . the use of negative pressure rooms with natural ventilation is recommended by the who guidance to prevent the spread of airborne pathogens among rooms [ , ] . first-aid materials and medicine such as oxygen tank, electrocardiogram (ecg) monitor, defibrillator, injection pump, infusion pump, endotracheal intubation supplies, portable vacuum extractor, noninvasive ventilator, invasive ventilator, hemofiltration equipment, extracorporeal membrane oxygenation (ecmo) equipment and so on should be prepared. other equipment, including air disinfecting machine and air cleaner, as well as medical gas systems including oxygen, compressed air, special gas, and vacuum suction systems, need to be assured too. it is of particular importance to implement effective measures to prevent the spread of covid- in icu. disinfection includes concomitant disinfection and terminal disinfection. concomitant disinfection must be conducted immediately for the materials and environment contaminated by the excretion of the suspected and confirmed patients. following the end of day's work in icu, or the patients' recovery or death in the isolation ward, terminal disinfection needs to be done carefully. key disinfection objects include patients' living supplies such as clothes and quilt, medical supplies, ground and wall space of icu wards, the surface of desks and bed tables, as well as air [ , ] . current evidence indicates that covid- is mainly transmitted from person to person through droplets, contact, and even high concentrations of aerosols [ ] . large amounts of droplets and aerosol are generated by sputum suction in the airway, specimen collection, tracheal intubation, fiber bronchoscopy, tracheotomy, etc. accordingly, surgeons are at a great risk of contamination. in order to avoid occupational exposure, recommendations during the aerosol-generating procedures in covid- patients are the following: statement if possible, covid- patients should probably be admitted to negative pressure rooms (grade +, weak recommendation). rationale negative pressure rooms are aimed to decrease the concentration of severe acute respiratory syndrome coronavirus (sars-cov- ) pathogens. in view of that, the risk of contamination would be decreased during the aerosol-generating procedures in such a setting. during the severe acute respiratory syndrome (sars) epidemic, it was reported that negative pressure settings were effective in preventing cross-contamination and protecting the staff and patients inside the room [ ] . according to who recommendations for covid- patients, such locations should be with a minimum of air changes per hour or at least l/ second/patient with natural ventilation [ ] . the experts suggest that operators wear a portable air-purifying respirator with level iii biosafety protection (expert opinion). rationale an observational study reported that among hospitalized patients diagnosed with confirmed covid- in zhongnan hospital in wuhan in january, , were healthcare workers [ ] . till march , , it has been reported that over health workers were confirmed with covid- , among whom died. the memory of what has happened during the sars outbreak is still fresh. a systematic review showed that the healthcare workers who performed aerosol-generating procedures, including endotracheal intubation (odds ratio, . ), noninvasive ventilation (odds ratio, . ), tracheotomy (odds ratio, . ), and manual ventilation before intubation (odds ratio, . ) were at higher risk of suffering from sars infection compared with the non-performers [ ] . most of the infections among healthcare workers occurred at the early stage of this outbreak when the self-protective directive has not yet been established and reinforced. after confirmation of human to human transmission of sars-cov- , the self-protection for healthcare workers was subsequently established and reinforced from the end of january . level iii biosafety protection is mandatory for intubation according to the guidance of the general office of the national health committee [ ] . ppe donning process should be strictly followed during high-risk operation: disposable hair cover, fit-tested n respirator or equivalent, fluid-resistant gown, two layers of gloves, goggle and face shield, and fluid-resistant shoe covers. the main operator should use portable airpurifying respirator. all the donning processes should be supervised by a professional nurse or assistant. doffing process of ppe after high-risk exposure should also be followed: hand hygiene, face shield and goggle removal, fluid-resistant gown removal, outer glove removal, shoe cover removal, inner glove removal, hand hygiene, n respirator or equivalent removal, and hair cover removal. the doffing process seems to be of greater importance. all the processes should also be supervised so as to reduce the risk of contamination [ ] . the aerosol-generating operations such as tracheal intubation and tracheotomy are suggested to be performed by senior physicians or specialists in the field. an electronic laryngoscope with light emitting diode is suggested during endotracheal intubation. if possible, disposable equipment is suggested to be used. b) fiber bronchoscopy is not suggested for patients without an artificial airway. the operation is suggested to be performed by senior physicians or professionally trained respiratory therapists. a bronchoscope with an external display is suggested for facilitating operations. if possible, the use of a disposable bronchoscope is suggested (expert opinion). rationale large amounts of aerosols generated by incubation can increase the risk of transmission and nosocomial infection [ ] . thus, visual devices are recommended to facilitate the procedure, limit operation time [ ] and ensure the distance between operator and patient. routine fiber bronchoscopy operations are not suggested for covid- patients. meanwhile, most covid- patients have few airway secretions [ ] so that the indication of bronchoscopy should be strictly minimized. according to the recommendations by the centers for disease control and prevention (cdc) [ ] and who [ ] , disposable medical equipment should be used for patient care if possible. statement (a) deep sedation (richmond agitation-sedation scale (rass): - ) is suggested for patients during the procedure of fiber bronchoscopy. (b) the artificial airway is suggested to be connected with a threeway connector allowing access to get into the airway to perform a bronchoscopy. (c) the use of a closed airway suction device is suggested (expert opinion). rationale severe covid- patients with artificial airway tend to suffer from severe hypoxemia [ ] . the patient's secretions, droplets, and aerosols can be widely spread during the operation. patients should be intubated within s [ ] . the procedure of fiber bronchoscopy should be performed gently with great caution in severe covid- patients. during bronchoscopy, following procedures should be followed to avoid aerosols spreading: artificial airway should be connected with a disposable three-way connector to a ventilator, then (a) ventilator needs to be set to standby mode, (b) the artificial airway needs to be briefly clamped, (c) the bronchoscopy should be quickly inserted into the connector, (d) the clamp should be opened, (e) ventilation should be restored [ ] . for the patients requiring mechanical ventilation, it is not advisable to disconnect patients from the ventilator. even though some clinical experts insisted that antiviral therapy is unnecessary for seriously ill patients with covid- since the course of disease in severe types is longer than weeks, multiple virus particles have been found at the lung lesions following histopathological examination. up to date, there is no specific antiviral drug that has been testified and globally recognized effective for treating covid- . in china, several antiviral drugs such as ribavirin, ganciclovir, oseltamivir, arbidol, alpha-interferon, chloroquine, lopinavir-ritonavir, and remdesivir have been used in clinical settings for the treatment of covid- . among them, oseltamivir and arbidol hydrochloride are the most commonly utilized; however, these antiviral drugs were originally designed for influenza, and their efficacy and safety for covid- need to be further investigated. no antiviral drugs are proven effective and should probably be considered for sars-cov- treatment (grade +, weak recommendation). rationale ribavirin is a broad-spectrum antiviral drug. clinical observations have suggested that early use of this drug is efficacious in containing covid- . to avoid possible aerosol transmission, we do not recommend alpha-interferon nebulization for covid- infected patients. according to a very recently published clinical study from france, hydroxychloroquine can significantly reduce viral load in covid- patients, and azithromycin can further enhance this effect [ ] . in this study, combination use of hydroxychloroquine (hcq) and azithromycin for at least days at an early stage could rapidly reduce the nasopharyngeal viral load and decrease the length of hospital stay for infected patients. it should be noted that treatment with higher chloroquine diphosphate (cq) dosage ( mg cq twice daily) is not recommended for severe covid- due to its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir [ ] . nonetheless, a randomized controlled trial (rct) trial conducted by cao et al. suggested monotherapy of lopinavir-ritonavir did not bring about any clinical benefits for severe covid- patients compared with standard supportive care, which may be partly caused by the higher throat viral loads in lopinavir-ritonavir group, delayed treatment initiation [ ] . of note, these clinical studies were limited by relatively small sample sizes. more large-scale and well-designed clinical trials are needed to confirm their potential therapeutic effects. arbidol monotherapy might be better than lopinavir-ritonavir in reducing viral load in covid- patients [ ] . a clinical study from gilead sciences showed that remdesivir could improve clinical conditions in critically ill patients with covid- , and stop patient from receiving invasive mechanical ventilation or ecmo [ ] . however, a recent multicentre study published in the lancet found no benefit of remdesivir in improvement of clinical outcomes for severe covid- [ ] . one recent study published in n engl j med showed that compassionate use of remdesivir improved clinical outcomes in a subset of severe covid- patients [ ] . however, the absence of control groups precludes a final conclusion. the definite therapeutic effectiveness of remdesivir in the treatment of severe covid- needs to be further verified. remdesivir has been approved as a potential treatment for severe covid- patients by the japanese ministry of health, labour and welfare (mhlw) on may , due to the covid- pandemic [ ] . the main side-effects of these antivirals include qt interval elongation, bradycardia, hepatic injury, and obvious gastrointestinal reactions such as serious diarrhea and vomiting which may contributed to disease deterioration. clinical trials testing remdisivir for the treatment of severe covid- patients are underway (nct , nct ). convalescent plasma therapy belongs to passive immunization, which is used for the treatment of virus infections when specific drugs and vaccines are unavailable. convalescent plasma, which has been used for more than one hundred years, can provide specific antibodies to neutralize and eradicate the viruses from the blood circulation. up to date, there is no particular treatment for covid- . in , the who recommended the use of convalescent plasma collected from patients who recovered from the ebola virus infection as an empirical treatment during the outbreak [ ] . during the covid- epidemic period, this method was also recommended by the national health commission of china for the treatment of severe and critical patients [ ] . statement convalescent plasma therapy should probably be used for severe and critically ill patients with covid- (grade +, weak recommendation). rationale convalescent plasma has been testified to suppress viremia, shorten the hospital stay, and reduce mortality during several virus epidemics. in during a spanish influenza pandemic, convalescent plasma reduced the mortality rate by > % in severe patients [ ] . since then, it was also used for prophylaxis or as a treatment for several virus infections such as measles, argentine hemorrhagic fever, influenza, chickenpox, and infection by cytomegalovirus. over the past two decades, its efficacy and safety were confirmed during pandemics of sars, mers, h n and h n avian flu. during the sars pandemic in , eighty patients received convalescent plasma at prince of wales hospital, hong kong. by the nd day, a higher discharge rate was observed in patients (n = ) given convalescent plasma before day than that given plasma after day ( . % vs. . %; p < . ) [ ] . a prospective cohort study conducted by hung et al. showed that convalescent plasma therapy (n = ) significantly reduced mortality compared to the control group (n = ) ( . % vs. . %; p < . ). meanwhile, plasma treatment lowered the upper respiratory tract virus load and decreased serum cytokines levels in patients with severe pandemic (h n ) virus infection [ ] . these studies verified the efficacy of convalescent plasma in patients with virus infections. it has been reported that among three severe mers patients who received convalescent plasma infusion, just two showed neutralizing activity [ ] . among five critically ill patients with covid- receiving mechanical ventilation convalescent plasma infusion, patients were discharged, while clinically ill patients improved and maintained the stable condition till the day after transfusion [ ] . a study performed in severe covid- patients found that convalescent plasma treatment could improve clinical outcomes, improve immune function, and promote absorption of lung lesions [ ] . nonetheless, just like any other treatment, convalescent plasma has its limitations. the main limitation refers to the reported studies, which are not randomized trials, but just prospective cohort studies or case series studies. therefore, it was not possible to eliminate the influence of baseline severity and other treatments when evaluating the effects of convalescent plasma therapy. other limitations include the risk of transmitting infections to transfusion service personnel, the need for adequate selection of donors with high neutralizing antibody titers, and the risk of other transfusion-transmitted infections [ ] . however, regardless of these limitations, since there are still no specific etiological treatments for covid- , and convalescent plasma is available, it is reasonable to use it in the treatment of covid- patients. respiratory failure is the primary organ dysfunction, which worsens the prognosis of covid- patients. oxygen therapy and respiratory support are the key treatments for covid- -induced ards. due to inflammatory and necrosis-induced small airway occlusion, which was confirmed by autopsy of covid- -induced ards, positive pressure ventilation is vital to restore the collapsed airway and improve gas exchanges. however, high end-inspiratory pressure increases stress and strain to normal alveoli and increases the risk of lung injury. oxygen therapy and respiratory support for covid- -induced ards should balance airway recruitment and risk of lung injury (fig. ). indication for hfnc and niv. statement niv and hfnc should probably be used for covid- -induced ards with pao / fio > mmhg (grade +, weak recommendation). rationale noninvasive ventilation support (niv) and hfnc are important treatments for covid- -induced mild and moderate ards. the mechanisms of the two treatments are positive end-expiratory pressure, decreased respiratory workload, decreased incidence of intubation, ease of use, and higher comfort. in a randomized trial of adult patients admitted to the icu for acute hypoxemic, nonhypercapnic respiratory insufficiency, continuous positive airway pressure (cpap) delivered by face mask was associated with an early improvement in oxygenation; however, it was not associated with a reduced need for intubation or with improved outcomes [ ] . a trial that compared hfnc oxygen, standard oxygen via face mask and face mask niv in patients with acute hypoxemic respiratory failure, reported that the intubation rate was significantly lower with hfnc oxygen than with standard oxygen or niv among patients with pao /fio ≤ mmhg at enrollment and, for the whole group (patients with pao / fio ≤ mmhg), patients managed with hfnc had improved survival. there were no differences in outcomes between niv and standard oxygen [ ] . a substudy examined the practice of niv use in ards of lungsafe study reporting that niv was associated with higher icu mortality in patients with a pao / fio < mmhg [ ] . for covid- , there is no sufficient evidence to prove that hfnc is superior to niv. statement when using niv and hfnc, oxygenation and breathing patterns are suggested to be closely monitored, and intubation delays is suggested to be avoided (expert opinion). rationale for all cases with noninvasive support, patients should be closely monitored, as deterioration can abruptly occur [ ] . in china, some patients presented with hypoxemia, later named "silence hypoxemia", since these patients were without corresponding clinical manifestations, e.g., no high respiratory rates, high heart rate, respiratory distress, and other hypoxia symptoms. these patients have a high risk of sudden death and should be closely monitored and timely provided with oxygen therapy. positive responses are usually evident soon after the initiation of niv and hfnc. if there is no substantial improvement in gas exchange and respiratory rate within a few hours, invasive mechanical ventilation should be started without delay. failure to recognize a lack of improvement during noninvasive support may result in further respiratory deterioration and/or cardiac arrest, often with devastating consequences. delayed intubation increases ards mortality; therefore, early recognition of ards severity could avoid delayed intubation. if the use of hfnc fails, endotracheal intubation is unavoidable even with the use of rescue niv [ ] . the indications for hfnc and niv intubation are a higher level of severity (saps ii score > ), hypoxemia (pao /fio ≤ mmhg), hypoxemia that is not improved following niv treatment for h, and strong spontaneous breathing (tidal volume with niv > ml/ kg pbw) [ ] . rox index can be used to predict hfnc failure and intubation for patients with respiratory failure; > . , suggests a high chance of success, < . suggests a high risk of failure, and intubating the patient should be discussed; index between . and . , suggests the patient should be monitored very closely and intubation delays should be avoided [ ] . [ , ] . another trial that employed a multilevel mediation analysis to analyze individual data from patients with ards, who were also included in nine previously reported randomized trials, identified driving pressure as the ventilation variable that best-stratified risk. decreases in driving pressure owing to changes in ventilator settings were strongly associated with increased survival [ ] . low tidal volume ( - ml/kg pbw), limited plateau pressure (< cmh o), and driving pressure (< cm h o) could decrease ards mortality. bedside measurements should probably be used for the evaluation of lung recruitability (grade +, weak recommendation). rationale alveolar collapse is mainly generated by inflammatory lung edema, impairment of chest wall movement, and surfactant deficiency. some reports have shown different effects of recruitment maneuvers in ards patients due to lung recruitability [ ] . from our experience in wuhan, most of the covid- patients had low lung recruitability [ ] . due to the infectiousness of covid- , ct, and the other necessary equipment cannot always be used to evaluate lung recruitability. however, some bedside measurements, such as the pressure-volume curve, recruitment to inflation ratio, and clinical parameters, can be measured by a ventilator and used to evaluate lung recruitability [ ] . based on low lung recruitability in covid- -induced ards, high peep should probably not be used, and peep setting should probably be based on various factors, including gas exchange, hemodynamics, lung recruitability, and driving pressure (grade +, weak recommendation). rationale use of positive end-expiratory pressure (peep) usually improves gas exchange and helps reduce the need for high fio . in addition, appropriate levels may limit vili by maintaining lung recruitment and improving lung homogeneity [ ] . when applied with a constant pplat, peep reduces the driving pressure and keeps the lung recruited. because of the lack of resources, peep selection criteria may include lung recruitability, peep/fio table, respiratory system compliance, optimal oxygenation, and driving pressure [ , , ] . based on the available data, all peep values represent a compromise between the extent of recruitment and overdistension, and hemodynamics. the experts suggest optimizing ventilator settings to improve hypercapnia (expert opinion). rationale in china, hypercapnia has been commonly found in covid- -induced ards. the mechanisms are related to lung injury inhomogeneity and an increase in dead space. firstly, optimization of ventilator setting is important; secondly, the prone position could decrease dead space and improve hypercapnia [ ] ; thirdly, tracheal gas inflation (tgi), which influences sputum drainage, could increase alveolar ventilation and co removal [ ] ; fourthly, extracorporeal life support or co removal equipment could improve hypercapnia. statement we recommend using prone positioning in severe covid- patients to prevent the deterioration of patients' condition (grade +, strong recommendation). rationale prone positioning has a beneficial effect on oxygenation, lung recruitment, and stress distribution. the physiological effects of prone positioning include redistribution of lung densities, often with the recruitment of well-perfused dorsal regions. although prone positioning increases chest wall elastance, this change is usually accompanied by improved lung recruitment, a reduction in alveolar shunt and improved ventilation/ perfusion ratio, subsequent improvement in oxygenation and co clearance, a more homogeneous distribution of ventilation and a reduced vili risk [ , ] . indications for prone positioning include moderateto-severe ards (pao /fio < mmhg), and/or hypercapnia. duration of prone positioning should be more than h, and the termination of prone positioning should be based on the response of oxygenation, lung mechanics, and hemodynamics. because prone positioning could improve lung inhomogeneity, early prone positioning should be provided for covid- infected patients with/without respiratory failure [ , ] since it could prevent respiratory failure. since covid- is highly infectious, implementation of the prone positioning might require more manpower, thus further increasing the workload of medical personnel. pressure injury of the skin and mucous, facial edema, corneal edema, displacement of the catheter, and airway obstruction must be avoided when placing patients in the prone position. most of the covid- patients presented with mild symptoms; however, about % of patients developed into severe cases, % of them were critically ill with mortality estimates of . − . % [ ] [ ] [ ] . mechanical ventilation alone may not be enough to resolve refractory hypoxemia and hypercapnia in these patients. ecmo could be initiated to maintain oxygenation and avoid ventilator-induced lung injury. a cross-sectional study found that ( . %) patients treated with ecmo [ ] . we recommend an early use of ecmo in covid- patients with refractory hypoxemia or hypercapnia who have received invasive mechanical ventilation and prone positioning (grade +, strong recommendation). rationale the appropriate timing of ecmo in covid- patients might be challenging due to enormous demand and uncertainty related to the reversibility of impaired lungs. to guarantee the reversibility of compromised lungs, ecmo should be launched before injurious mechanical ventilation, which is common in critically ill patients with covid- [ , ] . the primary purpose of ecmo is the maintenance of sufficient oxygenation, removal of co , avoidance of high respiratory drive, and sequencing of ventilator-induced lung injury. the following traditional indications for ecmo may be suitable for covid- patients: pao /fio < for over h; pao / fio < for over h; irreversible ph < . for over h. the experts suggest using the traditional indications for ecmo in hospitals with sufficient medical resources. however, for areas with poor medical resources, the indications for ecmo are suggested to be balanced between the available resources and expected outcomes (expert opinion). the who guidance released a statement, in which they suggest referring patients with refractory hypoxemia despite lung-protective ventilation to those settings with expertise in ecmo [ ] . the latest guidance document issued by elso also suggested that ecmo should be considered according to the standard management algorithm for ards in patients with viral lower respiratory tract infections [ ] . however, in reality, numerous patients who met the criteria for ecmo were admitted over a short period, which was beyond the capacity of the medical resource, including workforce and equipment. in this context, the priority of the ecmo supply should be balanced between the available medical resources and disease reversibility. younger patients with minor or no comorbidities should be given the highest priority when resources are limited. despite standard contradictions, patients who fit the criteria below may be excluded: ( ) patients with significant comorbidities; ( ) elderly patients with worsening prognosis; ( ) patients on mechanical ventilation for more than days. prone position, as well as other adjunct therapies should probably be used for critically ill patients even during ecmo (grade +, weak recommendation). rationale ventilation with the prone position, which is currently recommended by the guidelines, can improve lung heterogeneity as well as oxygenation [ ] . it should be considered in the early stages of the disease rather than as a delayed attempt [ ] . prone position ventilation is currently widely applied for severe covid- patients in china [ ] . even if an ultraprotective ventilation strategy is implemented with the aid of ecmo, prone ventilation is considered to benefit the recovery of the lung. elevated myocardial enzymes, such as cardiac troponin t (ctnt), creatine kinase (ck), creatine kinase-mb isoenzyme (ck-mb), have been widely observed in critically ill patients with the covid- , indicating potential myocardial injury. a significant elevation of myocardial enzymes often indicates a poor prognosis. most patients with elevated myocardial enzymes do not present compromised left ventricular systolic function (reduced ejection fraction) or abnormal electrocardiogram. left ventricular diastolic dysfunction or mild-to-moderate pulmonary arterial hypertension is common in some covid- patients. intensive hemodynamic monitoring should probably be considered for patients with hemodynamic instability. ecmo should probably be used for salvage therapy for patients with severe cardiac dysfunction (grade +, weak recommendation). rationale while sars-cov- and mers-cov share similar pathogenicity, it has been shown that mers-cov can induce acute myocarditis and heart failure [ ] . elevation of biomarkers of cardiac injury is common among critically ill patients with covid- and associated with a higher risk of in-hospital mortality [ , ] . reversible subclinical diastolic dysfunction without systolic impairment was observed in sars [ ] . comparable to sars, most covid- patients with elevated myocardial enzymes do not present compromised left ventricular systolic function. left ventricular diastolic dysfunction or mild-to-moderate pulmonary arterial hypertension have been commonly found in covid- patients. from our experience, tachycardia such as sinus tachycardia and atrial fibrillation were also common, while compensatory tachycardia was absent, even in patients with severe hypoxia or hemodynamic collapse. the exact mechanism of myocardial injury in covid- remains unknown. it has been suggested that direct myocardial injury is mediated via angiotensin converting enzyme (ace ). ace -dependent myocardial infection was observed in the murine model infected with sars-cov [ ] . one study published in n engl j med provides evidence that angiotensin-converting enzyme inhibitors (acei)/angiotensin receptor blockers (arb) medications in covid- patients did not show any association with increasing susceptibility to sars-cov- [ ] . in patients with hemodynamic instability, non-invasive or invasive monitoring, such as echocardiography or thermodilution methods, should probably be used to guide fluid therapy or administration of vasoactive agents. in patients with life-threatening cardiac dysfunction, extracorporeal life support might be salvage therapy. statement hypovolemia is common in critical covid- patients, easy-to-implement parameters should probably be considered for the assessment of the patient's volumetric status (grade +, weak recommendation). rationale the use of vasoactive drugs revealed that the incidence of shock in critically covid- patients was %, and % in non-survivor population [ ] . the shock could be the result of hypovolemia, cardiac injury, and sepsis. fever and mouth breathing could cause large amounts of fluid loss in critical covid- patients, while decreased water intake, acute gastrointestinal injury, depression, intubation, and sedation could exacerbate hypovolemia. previous studies reported on the relationship between dehydration and mortality in severe h n patients [ ] . moreover, older age, comorbidities (especially diabetes and cardiovascular disease), lower lymphocyte count, and higher d-dimer levels were identified as risk factors associated with shock [ , ] . cardiac injury was found in % critical covid- patients [ ] , which meant poor fluid responsiveness and the risk of pulmonary edema. for these reasons, the patients' volumetric status, as well as the fluid responsiveness, should be dynamically assessed. one meta-analysis of rcts showed that dynamic assessment of fluid responsiveness could improve the clinically relevant outcomes in icu, such as mortality reduction, reduced duration of icu length of stay, and mechanical ventilation [ ] . considering the limited clinical resources in the covid- pandemic, we recommend using simple bedside assessments, such as passive leg raising (plr), lactate clearance, pulse pressure variation (ppv), and inferior vena cava (ivc) collapsibility or distensibility. a recent meta-analysis determined that the plr induced changes in cardiac output, with a pooled sensitivity of . and a pooled specificity of . [ ] . ppv also accurately predicted fluid responsiveness in critical patients. in a meta-analysis including studies and patients, ppv predicted fluid responsiveness with the pooled sensitivity of . and a pooled specificity of . [ ] . ivc collapsibility resulted as a simple, non-invasive bedside predictor of fluid responsiveness with a sensitivity of . and a specificity of . [ ] . early lactate clearance-directed therapy was associated with reduced in-hospital mortality, shorter duration of mechanical ventilation, and shorter icu-stay [ ] . a recent observational study showed higher serum lactate levels in covid- non-survivors ( . vs. . mm/l) [ ] . besides, additional attention should also be paid to mental states, degree of thirst, oliguria, skin temperature, and prolonged capillary refilling time as well. conservative fluid strategy should probably be considered for covid- patients with ards while ensuring tissue perfusion (grade +, weak recommendation). rationale even though fluid management in covid- remains unknown, it could be assumed that these patients would respond to fluid therapy in the same way as other ards patients. previous studies have shown that higher cumulative fluid balance is related to the higher mortality of critically ill patients, especially in cases of ards [ ] and/or septic shock [ ] . due to pulmonary edema in critical covid- patients [ ] , excessive fluid therapy could increase extravascular lung water and affect gas exchange, resulting in a poor prognosis. one clinical trial found that the conservative fluid strategy improved lung function, shortened the icu-stay length and duration of mechanical ventilation compared with a liberal strategy in patients with acute lung injury [ ] . another study reported that more than half of critically covid- patients were older than years [ ] . when older patients develop cardiac injury and pulmonary edema, they tend to be less responsive to fluid intake [ ] . conservative fluid strategies could reduce the occurrence of positive fluid balance while ensuring tissue perfusion [ ] . although it has been reported that conservative fluid strategy and liberal strategy have a similar incidence of aki and the requirement for renal replacement therapy (rrt) [ ] , it is still necessary to closely monitor the renal function of patients. at the same time, attention should be paid to maintaining electrolyte balance and acid-base balance. rationale to date, there are still no studies on fluid types in covid- patients; thus, our observations are based on relevant studies of critically ill patients in general. a systematic review of studies that included , participants revealed that using colloids (such as starches, dextrans, albumin or fresh frozen plasma, or gelatins) had no difference in mortality in critically ill patients compared to crystalloids [ ] . considering the price and accessibility, fluid resuscitation with crystalloids should probably be used for critically ill patients. one single-center research reported that low serum albumin ( . ± . g/l) was associated with the progression of covid- pneumonia [ ] , while another study found no significant differences between the nonaggravation and aggravation patients in the early stage of the disease [ ] . serum albumin level < g/l was identified as an independent risk factor for the -day mortality in patients with community-onset pneumonia [ ] . based on the previous evidence and our clinical observations, hypoproteinemia is present in most covid- patients; thus, albumin supplement should probably be used for patients with serum albumin levels below g/l. statement psychological and humanistic care should probably be considered for conscious patients with covid- (grade +, weak recommendation). rationale besides experiencing physical impairment and stressful treatments, covid- patients are being subjected to closing monitoring, and are also witnessing various events in the ward such as sudden deterioration of illness, emergency resuscitation procedures and death, all of which could lead to posttraumatic stress disorder, anxiety, and depression according to previous studies [ , ] . it was reported that % to % of sars survivors had symptoms related to posttraumatic stress disorder, anxiety, and depression and that emotional support, such as communication with others and sharing worries could reduce symptom severity [ ] . accordingly, psychological implications should not be ignored in coronavirus patients. psychological health services and humanistic care could have an important role in rehabilitation. the previous study confirmed that citalopram could improve reappraisal ability and anxiety symptoms in children and adolescents [ ] and that olanzapine could improve psychotic symptoms [ ] . therefore, citalopram or olanzapine should probably be used to improve the psychological symptoms in patients or intervention of the psychologists in the isolation ward who would perform psychological assessment and psychotherapy for patients with new coronary pneumonia. the experts suggest assessing patients' sleep quality, implementing comprehensive measures to improve sleep and reduce the incidence of delirium, thus promoting recovery (expert opinion). nonpharmacological strategies and pharmacotherapy, including dexmedetomidine and melatonin, should probably be considered to decrease the incidence of delirium (grade +, weak recommendation). rationale sleep abnormalities, including abnormal sleep architecture, sleep deprivation, and disruption, frequently occur in the icu. numerous factors can affect sleep in covid- patients, such as stress, anxiety, pain, respiratory distress, tachypnea from the underlying hypoxemia, noise levels, stage lighting in the isolation ward, implementation of healthcare, procedures of healthcare workers, and the pathophysiology of the acute illness. sleep abnormalities may not only lead to mental disorders, but could also damage tissue repair, immune regulation mechanisms and cause delirium, all of which are associated with patient's poor prognosis [ , ] . nonpharmacological strategies for preventing sleep disturbances and treating delirium, such as keeping noise levels within and db range (a) during the day, and less than db (a) at night [ , ] , and providing critical patients admitted to the icu with earplugs can significantly improve patient's sleep and reduce the risk of delirium [ ] . however, in patients with sleep disturbances and delirium, pharmacotherapy care may be necessary. medications such as dexmedetomidine [ ] and melatonin [ , ] may promote sleep and decrease the incidence of delirium, although only limited data are available in support of their use [ ] . assessing pain and preferential use of analgesia over sedation should probably be considered for covid- patients (grade +, weak recommendation). rationale pain is defined as an uncomfortable physical and mental experience caused by physical injury, inflammation, or emotional stimuli. covid- patients tend to experience pain due to hypoxia, long-term immobility, inflammatory storm, impairment of heart, liver, kidney, and other organ functions, procedures, and mental stress. opioids, such as remifentanil and sufentanil, are the firstline options for analgesia in icu according to the pain, agitation/sedation, delirium, immobility, and sleep disruption (padis) guidelines [ ] . sufentanil can be used for covid- patients receiving invasive mechanical ventilation during the early stage of severe ards because of its stronger and faster onset of analgesia, and small accumulation [ ] . remifentanil is suitable for covid- patients receiving invasive mechanical ventilation, especially during person-ventilator confrontation [ ] due to stronger respiratory depression. previous research has confirmed that music or relaxation may diminish anxiety and discomfort in some patients [ , ] . therefore, nonpharmacological pain management strategy can be used for conscious patients with covid- or for patients who do not tolerate opioid therapy, such as covid- patients receiving hfnc oxygen therapy or non-invasive mechanical ventilation. assessment of the patient's pain is the foundation of pain management. accordingly, a numeric rating scale (nrs) should probably be used for evaluation of pain in all covid- patients able to self-report their pain. behavioral pain scale (bps) and critical-care pain observation tool (cpot) should be used to evaluate pain in critically ill patients unable to express the pain for themselves. the ideal target values are: nrs < points, bps < points and cpot < points. deep sedation should be performed for patients with severe ards, especially those receiving invasive mechanical ventilation, prone position, neuromuscular blockade, or ecmo treatment (grade +, strong recommendation). rationale it is well known that analgesia and sedation can eliminate pain and discomfort, reduce sympathetic nerve excitement, patient's metabolic rate, oxygen consumption, the metabolic burden of various organs, stress, and inflammation. however, plenty of evidence suggests that deep sedation is associated with adverse outcomes, including prolonged mechanical ventilation and icu-stay, higher mortality, lower rates of in-hospital, and -year follow-up survival [ ] [ ] [ ] [ ] [ ] . under 'real-life' conditions in wuhan, deep sedation was extremely important for reducing oxygen consumption and developing tolerance to mechanical ventilation by new coronavirus patients with severe ards who suffered from respiratory distress, tachypnea and respiratory overdrive even after receiving invasive mechanical ventilation. accordingly, deep sedation should be an important part of lung-protective ventilation strategy, especially during the early stage of severe ards. previous studies have confirmed that daily spontaneous awakening trials (interruption of sedatives) lead to better outcomes in patients receiving mechanical ventilation [ ] . however, critically ill patients with covid- have a longer mechanical ventilation time, and daily sedatives interruption is not suggested for patients receiving deep sedation in order to reduce lung damage during early stage of severe ards. midazolam and propofol are the primary medications used for icu deep sedation. the sedation-agitation scale (sas) and rass are the reliable and valid sedation assessment tools used for assessing the depth and quality of sedation in covid- patients. the sas and rass should be used to measure the depth after administering sedatives. the target value is rass - - points, sas points for deep sedation, and sas point. the target value of very deep sedation is rass - point for patients receiving neuromuscular blocking agents [ ] , prone position, or ecmo treatment. we suggest a bispectral index monitoring for patients undergoing very deep sedation, if available. light sedation is suggested for severe covid- patients receiving hfnc oxygen therapy and non-invasive mechanical ventilation, and also for critically ill patients in the recovering stage (expert opinion). rationale agitation and anxiety, which frequently occur in covid- patients, may be associated with adverse outcomes. appropriate sedation can reduce anxiety and agitation while preserving patients' comfort. light sedation can maintain frequent redirection, and increase the physiologic stress response, but not increase the incidence of myocardial ischemia. we suggest the use of light sedation for covid- patients receiving hfnc oxygen therapy or non-invasive mechanical ventilation. in addition, light sedation should be given to recovering patients in order to reduce the time of mechanical ventilation and the time of stay in icu [ ] when pao / fio ≥ - mmhg. dexmedetomidine can be used for patients receiving light sedation due to the small respiratory depression. the target value of light sedation is sas - points and rass − to + points. there is some evidence that immunotherapy may be effective against novel coronavirus infection. an article [ ] published on the medrixv website stated that the mortality of covid- patients might be negatively related to the number of lymphocytes in patients. patients tend to be below normal levels and lower level of helper t cells in the severe group. the percentage of naïve helper t cells increased, and memory helper t cells decreased in severe cases. this suggested that novel coronavirus might fight the immune system; thus, early lymphocytes and t lymphoid subgroups testing are required for early intervention, which may help to avoid lymphocyte depletion. currently, there are several available immunomodulatory drugs, including glucocorticoid, thymosin, and immunoglobulin. statement systemic corticosteroids should probably not be used for the treatment of covid- . for critically ill patients with ards at an early stage, corticosteroids should probably be prudently used at a low or moderate dose over the short course if there are no contraindications (grade -, weak recommendation). rationale glucocorticoid use in ards remains a controversial topic. it is well known that corticoids are beneficial in the treatment of ards since they can alleviate inflammatory response and delay fibrosis [ ] . a retrospective study conducted in guangzhou revealed that proper use of corticosteroids in confirmed critical sars patients led to lower mortality and shorter hospitalization stay and was not associated with significant secondary lower respiratory infections or any other complications [ ] . however, there are some inconsistencies in the existing studies. a study involving patients with ards, showed improved oxygenation and lung injury score in less than h but no change in -day mortality [ ] . another study found no differences in overall mortality, while mortality was increased when steroids were started after day [ ] . as for viral pneumonia, a few studies have found that the administration of corticosteroids in patients with influenza pneumonia is associated with increased icu mortality [ , ] . who does not recommend routine use of corticoids in the treatment of covid- , while treatment with methylprednisolone may be beneficial for patients who develop ards, as was shown by a retrospective cohort study of patients with confirmed covid- pneumonia admitted to wuhan jinyintan hospital in china [ ] . given the inconclusive evidence and urgent clinical demand, the guidance published by china national health commission on march , , suggested the use of glucocorticoids over the short time period ( to days) for patients with progressive deterioration of oxygenation indicators, rapid imaging progress, and excessive activation of inflammatory response. the dosage of methylprednisolone should not exceed - mg/kg/day. it should be noted that large doses of glucocorticoid might delay the removal of coronavirus due to immunosuppressive effects. thymosin is a peptide originally isolated from thymic tissue, which was initially selected for its ability to restore immune function to thymectomized mice. thymosin may act on precursor t cells to increase the number of activated t helper cells and expression of th -type cytokines such as interleukin- and interferon-alpha. the activated dcs and th cells then kill bacterial, fungal, or viral infections and lead to the stimulation of differentiation of specific b cells to antibody-producing plasma cells and an improvement in response to vaccines by stimulation of antibody production [ ] . the use of thymosin alpha therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis [ ] . also, it has been observed that lower lymphocytes in covid- patients indicate worse prognosis [ ] . thus, thymosin may theoretically have an effect on covid- , which needs to be further investigated. immunoglobulin may regulate the host's immune response in a variety of ways, but it had no effect on mortality in previous sepsis studies. at present, it is not recommended in the treatment of covid- . a study performed in severe or critical covid- patients showed that tocilizumab treatment could improve clinical outcomes, promote absorption of lung lesions, improve immune function, and reduce inflammatory response [ ] . however, il- inhibitor sarilumab was shown to be ineffective in the treatment of severe covid- , leading to early termination of this clinical trial [ ] . large sample size studies using prospective cohort designs are required to verify the therapeutic effect of il- inhibitors for severe covid- . great attention should be paid to secondary infection since it may worsen the patient's prognosis. however, since the data on the epidemiology of secondary infection in covid- patients are lacking, we can only make some suggestions according to our own experience and some previous studies focused on h n . the experts suggest against using prophylactic antibiotics for covid- patients (expert opinion). rationale due to the nature of virus infection, it is not logical to use prophylactic antibiotics, and there is no evidence that this strategy could reduce the incidence of the secondary infection. on the other hand, according to the management guidelines of covid- from who and china [ , ] , empiric antibiotic treatment should only be used based on the clinical diagnosis (communityacquired pneumonia, healthcare-associated pneumonia or sepsis), local epidemiology and susceptibility data, and treatment guidelines. based on our observations from wuhan, many severe and critical covid- patients did not show any signs of bacterial infection (such as elevated wbc, pct and similar); thus, we do not suggest the routine use of prophylactic antibiotics in covid- patients, especially at the early stage or for non-intubated patients. the experts suggest closely monitoring the signs of secondary infection, especially in critically ill patients with covid- who have been admitted to icu > h (expert opinion). rationale both long course of the disease and immunosuppressive state place the severe and critical covid- patients at a high risk of secondary infection (including bacteria and fungus). unfortunately, the data on the epidemiology of secondary infection in covid- patients are lacking. however, based on the evidence from h n , secondary infection is very common in patients admitted to icu > h [ , ] . although a complete nosocomial infection prevention and control system was set up in wuhan according to the guidelines [ , ] , ventilator-associated pneumonia and hospital acquired pneumonia were very common occurrences in the icu. we suspect this is mainly because the medical staff is wearing heavy personal protective equipment, and heavy workload adhered to the incomplete implementation of these measures. consequently, the strategies for nosocomial infection prevention should be effectively implemented, and multiple site samples (blood, sputum, etc.) should be routinely collected to monitor the signs of secondary infection. in clinical practice, coagulation dysfunction is commonly found in covid- patients, and the symptoms range from mild disorders of coagulation indicators to disseminated intravascular coagulation (dic). the exact etiology of covid- -associated coagulopathy is unclear, diverse and multifactorial, and may include direct attack by the sars-cov- on vascular endothelial cells, cytokine storm-mediated inflammation-coagulation cascades, hypoxia, and complication with sepsis. coagulation dysfunction or thrombocytopenia is closely associated with the severity and poor prognosis in covid- patients [ ] . clinicians should increase awareness of covid- -associated coagulopathy, which in covid- patients is accompanied with the following abnormal coagulation indexes: platelet-lymphocyte ratio < × , the reduction of prothrombin time (pt) and activated partial thromboplastin time (aptt) by more than the lower limit of th percentile or the increase of pt by more than s or aptt by more than s, or the increase of fibrinogen, fibrin degradation product (fdp) and d-dimer by more than the lower limit of th percentile without clinical evidence of primary blood system diseases or chronic liver diseases. routinely assessing the coagulation dysfunction on admission and dynamically monitored thereafter should probably be performed to identify covid- -associated coagulopathy as early as possible (grade +, weak recommendation). rationale according to the available literature, the condition of covid- patients is commonly complicated with coagulopathy, where the symptoms range from mild disorders of coagulation indicators to dic. the increase of d-dimer in covid- patients is very common, accounting for % to . % of all cases [ , , , , ] . the degree of elevation and persistent elevation are indicators of poor prognosis. the nanshan zhong team has reported that among covid- patients in hospitals from provinces ( mild cases and severe cases), the proportion of severely ill patients with d- dimer higher than . mg/l was up to . %, and the proportion for the mild patients was . % [ ] . zhou et al. have demonstrated that among confirmed covid- patients ( deaths, survival), d-dimer > . g/l was an independent risk factor for clinicians to identify patients with poor prognosis at the early stage [ ] . the coagulation parameters (pt and aptt) in covid- patients vary with different severity and the different courses of the disease. covid- patients in the early stage show the activation of the exogenous coagulation system, manifested as decreased pt and hypercoagulable state. along with the progression of the disease, especially when patients develop dic, pt and aptt significantly increase, which is associated with the poor prognosis of patients. tang has reported increased fibrinogen ( . g/l vs. . g/l, p = . ) and fdp values ( . µg/ml vs. µg/ml, p < . ) in covid- patients [ ] , which indicated that instead of hyperfibrinolysis observed in the late stage of dic, fibrinolysis inhibition is the main feature accompanying the progression of covid- . the autopsies of covid- patients have revealed abundant transparent thrombus in the pulmonary alveoli, myocardium, portal area, and renal tubular epithelial cells, thus indicating that fibrinolysis inhibition may have a decisive role in covid- -associated coagulation dysfunction. the incidence of dic is low in covid- patients. it has been reported that among the covid- patients, only patient ( . %) was diagnosed as dic [ ] . however, tang's report has shown that the overall incidence of dic is . %. the existence of dic was more common in fatal cases, where . % met the isth diagnostic criteria for dic; the median time for dic diagnosis after admission was days, whereas among the patients who survived, only patient ( . %) met this criterion [ ] . medical institutes should dynamically detect the pt, international normalized ratio (inr), aptt, d-dimer, fibrinogen, and fdp to identify covid- -associated coagulation disorders, which might be helpful for making timely treatment decisions. it is also suggested to use the isth score system to diagnose covid- -associated dic [ ] ; if possible, sf and pai- should be used to detect the pre-dic status in the shortest possible time. routinely evaluating the risk of venous thromboembolism (vte) and hemorrhage should probably be performed in covid- patients. for critically ill covid- patients with low hemorrhage risk, subcutaneous injection of low molecular weight heparin (lmwh) should probably be used for preventing vte (grade +, weak recommendation). rationale the most common clinical features of coagulopathy in covid- patients are thrombosis in the deep vein or intermuscular vein of the lower extremity, which can be identified by the coagulation parameters and ultrasonic monitoring. it has been reported that the incidence of vte or thrombotic complications in patients with severe covid- admitted in the icu was - % [ , ] . it is necessary to pay attention to the clinical observation of patients with bed rest lasting for more than days and observe whether these patients are experiencing asymmetric pain, swelling or discomfort in unilateral lower limbs or bilateral lower limbs, or local swelling or superficial vein filling in the lateral limbs. especially when patients show chest pain, hemoptysis, dyspnea, or hypoxemia, which cannot be explained by ncp or other basal diseases, we should be alert to the occurrence of pulmonary thromboembolism. for critically ill covid- patients with low hemorrhage risk, a subcutaneous injection of lmwh should probably be used for the prevention of vte. for patients with severe renal dysfunction (creatinine clearance rate < ml/min), unfractionated heparin is recommended. for critically ill patients whose condition is complicated with high hemorrhage risk, intermittent pneumatic compression is recommended for mechanical prevention. mild or moderate covid- patients should probably avoid sedentary lifestyle or dehydration and are encouraged to engage in active activities and to drink more water appropriately. for mild or moderate covid- patients with a high or moderately high risk of vte according to the padua or caprini evaluation model, it should probably be considered to use lmwh for to days until the elimination of risk factors. anticoagulation therapy should probably be used for patients with hypercoagulant state without bleeding risk. lmwh or unfractionated heparin should probably be considered to be the first choice (grade +, weak recommendation). rationale hypercoagulant state is common in covid- patients. meantime, cytokine storm-mediated inflammation-coagulation cascades may have an essential role in covid- -associated coagulopathy. studies have found that in addition to the anticoagulant effect, heparin also has a certain anti-inflammatory effect [ ] . therefore, lmwh or unfractionated heparin is the first choice for anticoagulation: tang et al. have reported that lmwh or unfractionated heparin anticoagulation was associated with improved survival in the patients with a sepsis-induced coagulopathy (sic) score ≥ and in those with d-dimer levels more than times of the upper limit of normal(≥ mg/l) [ ] . it is suggested that lmwh u/kg or unfractionated heparin units subcutaneously twice daily could be given to patients without contraindication once d-dimer ≥ mg/l or sic ≥ . heparin-induced thrombocytopenia (hit) should be prevented during heparin treatment, and platelet counting should be monitored daily. for patients with hit, other anticoagulants, such as agatraban, bevaludine, fondaparinux, and rivaroxaban, could be used. for patients at high risk of bleeding, anticoagulants are not recommend, and chinese traditional medicine could be used to improve blood circulation and dispersing stasis. although diffuse alveolar damage and ards are the main features of covid- , the involvement of the kidney and other organs needs to be considered. aki was associated with a higher risk of in-hospital mortality. clinicians should increase awareness of aki in hospitalized covid- patients. kidney disease: improving global outcomes (kdigo) criteria should probably be used for the diagnosis of aki in covid- patients. measuring serum creatinine every days should probably be performed to avoid a missed diagnosis of aki (grade +, weak recommendation). rationale the incidence of aki in covid- patients varies with different severity of illness: mild cases have an aki incidence of . - %, severe cases have an aki incidence of - . %, and the aki incidence for those critical cases that require to be admitted in icu is up to . - % [ , , , , ] . according to kdigo aki diagnostic criteria, certifying aki is mainly based on changes in scr, and the frequency of scr tests has a substantial impact on the detection rate of aki. in a nationwide cross-sectional survey of hospitalized adult patients in china, the detection rate of aki was only . % by kdigo criteria [ ] . after adjusting for the frequency of scr, the incidence of aki in chinese hospitalized adults rose to . % [ ] . thus, in order to improve early recognition of aki, scr measurements should be performed more frequently throughout the course of the disease. it is necessary to measure scr every days throughout the course of the disease to avoid a missed diagnosis of aki. the experts suggest using standard aki care bundle ( r principle) for covid- -associated aki (expert opinion). rationale the exact pathogenesis of covid- associated aki is unclear. the etiology of kidney impairment in covid- patients, which is likely to be diverse and multifactorial, may include direct attack by the sars-cov- on target cells in the kidney, immune systemmediated damage, disease-related prerenal factors, a complication with sepsis and nephrotoxic drug-related factors [ , ] . covid- associated aki is an independent risk factor for poor prognosis in patients. clinicians should address standard aki following r principle (risk screen, recognition in the early phase, response in time, renal replacement therapy, and rehabilitation of the kidney). aki is significantly more likely to develop in severe covid- patients than in nonsevere patients [ , , , , ] . meanwhile, studies have shown that patients with elevated baseline scr are more likely to develop aki and develop more severe aki [ ] . therefore, we should routinely screen the risk of aki in covid - patients, particularly for severe cases, patients with elevated baseline scr or those having proteinuria and hematuria at admission. optimizing the volume status and oxygenation, maintaining hemodynamic stability, making sure the mean blood pressure above mmhg are the important measures for prevention and treatment of aki. the experts suggest using crrt for the critical cases accompanied by kidgo aki - stages, or cytokine storm syndrome (expert opinion). rationale according to the available literature [ , , , , ] , the percentage of covid- patients who require continuous renal replacement therapy (crrt) is . - %, and particularly the percentage of critical patients admitted in icu that requires crrt is . - . %. indications of the crrt in covid- patients include renal indications and non-renal indications. renal indications include severe aki (kidgo aki - stages) with hemodynamic instability. non-renal indications include complications with severe ards and persistent inflammatory fever, which cannot be controlled not even with glucocorticoid corticosteroid therapy, hypernatremia refractory to conservative medical treatment, volume overload or urine output, which cannot meet the needs of drug infusion and energy supply and diuretic resistance. multiple rct research has indicated that the application of crrt in critical patients in an early phase cannot effectively decrease the mortality rates [ , ] . however, considering the suggestion that restrictive fluid volume management strategy should be adopted for covid- patients complicated by ards based on the premise of sufficient tissue perfusion, we suggest crrt initiation in severe patients within h when they show rank aki under kdigo criteria or accompanied with cytokine storm syndrome. in clinical practice, the doctors in charge should comprehensively evaluate conditions including the covid- patient's level of systemic inflammation, severity and progress of illness, severity, and progress of aki, local medical resources, and the qualification of blood purification operators to give a reasonable choice of crrt application. statement crrt prescription is suggested to be target-oriented based on the patient's condition (expert opinion). rational crrt prescription should be prescribed before the application of crrt on patients, and the prescription must be target-oriented. continuous venovenous hemofiltration (cvvh) global surveillance for human infection with coronavirus disease (covid- ) world health organization. coronavirus disease (covid- ) situation reports clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected the novel coronavirus pneumonia emergency response epidemiology team. the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- )-china clinical 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espen guideline on clinical nutrition in the intensive care unit calorie intake of enteral nutrition and clinical outcomes in acutely critically ill patients: a meta-analysis of randomized controlled trial gudielines for the provision and assessment of nutrition support therapy in the adult critically ill patient: society of critical care medicine (sccm) and american society for parenteral and enteral nutrition clinical nutrition in critical care medicine-guideline of the german society for nutrition medicine(dgem) recommendations for nutrition therapy in critically ill covid- patients safe patient transport for covid- publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. all the authors have participated in literature retrieval, viewpoint discussion, and writing the manuscript. all authors read and approved the final manuscript. none. not applicable. not applicable. not applicable. the authors declare that they have no competing interests. key: cord- -q igdvq authors: ryan, donal; frohlich, stephen; mcloughlin, paul title: pulmonary vascular dysfunction in ards date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: q igdvq acute respiratory distress syndrome (ards) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (ph). multiple factors may contribute to the development of ph in this setting. in this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ards and reported on mortality in the period to . there were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. in order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. we consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ards, including the important effects of mechanical ventilation. pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (tpg) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. the great variability in management strategies within and between studies means that no unified analysis of these papers was possible. uniquely, bull et al. (am j respir crit care med : – , ) have recently reported that elevated pulmonary vascular resistance (pvr) and tpg were independently associated with increased mortality in ards, in a large trial with protocol-defined management strategies and using lung-protective ventilation. we then considered the existing literature to determine whether the relationship between pvr/tpg and outcome might be causal. although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. nonetheless, abnormally elevated pvr/tpg may provide a useful index of disease severity and progression. further studies are required to understand the role and importance of pulmonary vascular dysfunction in ards in the era of lung-protective ventilation. acute respiratory distress syndrome (ards) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension [ ] . the single biggest advance in the management of ards has been the institution of lung protective ventilation (ardsnet) [ ] . however, mortality remains unacceptably high, ranging from the % to % reported in randomised controlled trials up to % in published observational studies [ , ] . intensivists and researchers have long been aware of the occurrence of pulmonary hypertension and cor pulmonale in ards. however, there has been uncertainty about the underlying pathophysiology and the link between the degree of pulmonary hypertension and outcome from ards. is pulmonary hypertension simply an indicator of the severity of lung injury or is it part of the underlying pathophysiological process contributing to the development of ards? recent studies have pointed to the importance of pulmonary vascular dysfunction (pvd) in predicting mortality from ards [ ] , but the exact mechanism by which pvd and mortality are linked is not known. the focus of this review is to examine the nature of the relationship between pulmonary hypertension/pvd and mortality in ards. studies were identified after a literature search using key terms (ards or acute respiratory distress or ali or acute lung injury) together with any of the following: pulmonary haemodynamics, pulmonary artery pressure, pulmonary vascular resistance, pulmonary vascular dysfunction, right ventricle, right ventricular failure, acute cor pulmonale, or pulmonary artery catheter. the references of articles found in this manner were also examined for similar studies. manuscripts that reported a relationship between pulmonary haemodynamics and mortality in ards/ali were included. in addition, papers that reported a relationship between right ventricular failure/right ventricular dysfunction and outcome were included. we have included definitions of commonly used terms in this article in table . many indices of pulmonary haemodynamics have been measured in patients with ards. pulmonary arterial pressure, wedge pressure and pulmonary vascular resistance have all been reported as well as measures of right ventricular function. the two most commonly reported measures are pulmonary arterial pressure and pulmonary vascular resistance. a number of studies (table ) have documented the changes in pulmonary haemodynamic measurements in patients with ards. all measurements were derived from the use of pulmonary artery catheter except for the study by cepkova [ ] , where pa systolic pressures were estimated using echo. some of these studies are small, and the majority were conducted before the widespread introduction of low tidal volume ventilation. nevertheless, certain observations can be made from the data. mild to moderate elevations in mean pulmonary artery pressure (mpap) are seen in most patients with ards [ , ] . squara et al. found moderate elevation in mean pulmonary pressure in patients, h after the diagnosis of ards [ ] . patients with worse pao /fio ratios had higher mpap than those with better oxygenation ( . ± . vs. . ± . mmhg, p = . ). systolic pulmonary arterial pressure (pap) was deemed to be of 'independent and sustained prognostic significance during the course of ards'. in a later study, osman et al. also found mpap to be an independent predictor of mortality in a multivariate model [ ] . other studies either found pap not to be predictive of death or else did not specifically examine for a relationship [ , [ ] [ ] [ ] [ ] ] . in patients with severe ards, beiderlinden et al. [ ] found an incidence of pulmonary hypertension of . % but did not find any association between pulmonary hypertension and death. hemilla et al., in a review of patients with severe ards who subsequently received ecmo, found evidence of moderate pulmonary hypertension using pulmonary artery catheter data acquired prior to the institution of extracorporeal support [ ] . again, direct measurements of pap were not identified as being of prognostic significance. pulmonary vascular resistance (pvr) is known to be elevated in patients with ards (tables and ). zapol and jones were the first to document that raised pulmonary vascular resistance was a common finding in patients with severe respiratory failure [ ] . they observed that pulmonary vascular resistance tended to fall in survivors but remained elevated in those who died. this is the only study to report pulmonary haemodynamic indices longitudinally. zapol and jones subsequently documented a threefold elevation in pvr in patients with ards [ ] . these in a secondary analysis of the haemodynamic data from the fluid and catheter treatment (factt) trial of patients with ards who were managed with a pulmonary artery catheter, bull et al. showed that the transpulmonary gradient (mpap-pulmonary arterial occlusion pressure (paop)) and the pulmonary vascular resistance index (mpap-paop/ci) were the only pulmonary haemodynamic indices that showed a significant difference between those who died and those who survived. multivariate analyses showed them to be independent predictors of mortality in ards [ ] . they used the term 'pulmonary vascular dysfunction' to describe these two variables. covariates in their multivariate analyses included sex, race, age, apache ii score, the presence of shock at baseline, level of positive end-expiratory pressure (peep), the pao :fio ratio and fluid treatment strategy. they did not find any difference in p:f ratios, pasp, padp, mpap, paop or cardiac index between those who survived with ards and those who did not. the pplat and peep levels were not different among the groups. it is worth noting that % of the screened patients were excluded because they had a pulmonary artery catheter in place at the time of randomization and that % of the enrolled patients showed a paop > mmhg at enrollment, therefore not meeting the abc definition of ards. this may have explained why the pap-paop gradient may have been significant, when pap was not. there are marked differences among these studies, with some showing that pulmonary arterial pressure is independently associated with mortality, and in others' findings, it is not. similarly, increased pvr was found to be a predictor of adverse outcome in some studies and not in others. before considering these discrepancies in more detail, it is helpful to examine the relationship between pap and pvr in healthy subjects and to look at the pathophysiology of elevated pulmonary vascular resistance. there is a complex, non-linear relationship between pulmonary arterial pressure and pulmonary vascular resistance in normal, non-diseased lungs. in the lungs, the pvr is conventionally calculated as follows: where pvr = pulmonary vascular resistance, mpap = mean pulmonary arterial pressure, lap = left atrial pressure and co = cardiac output. in the systemic circulation, an ohmic relationship between driving pressure and flow through the blood vessel provides a reasonable approximation ( figure a ). in such a system, the plot of pressure against flow is a straight line passing through the origin and the resistance to flow is well characterised as the ratio of the arterial pressure to the flow (cardiac output) at all points along the pressure flow line. in contrast, the blood flow through the lungs is not well described by a linear relationship passing through the origin but by a curvilinear plot that has a positive intercept on the pressure axis ( figure b ). this curvilinear relationship arises because of the marked distensibility of the pulmonary vasculature. an increase in pulmonary arterial pressure results in an increased flow due both to the higher driving pressure and the distension of the vessels so that the diameter of the vascular lumen is increased. thus, increases in pulmonary arterial pressure have a disproportionate effect on pulmonary blood flow. as a consequence, a reduction in cardiac output leads to an increase in the ratio of the pressure drop across the pulmonary circulation (pap-lap) to flow, even though there is no change in vasomotor tone ( figure b ). blood flow through the lungs also depends on the transmural pressure in the pulmonary vessels (pressure within lumen minus airway pressure) to a much greater extent than in systemic vessels. airway pressure can have a marked effect on pulmonary blood flow, as originally determined by west [ ] . lung volume has an important effect on pvr which is independent of vascular transmural pressure. whittenberger et al. [ ] described how low (near residual volume) lung volumes were associated with a slight elevation in pvr (extra-alveolar vessels are narrowed) and high lung volumes (near total lung capacity) were associated with the highest pvr (alveolar capillaries are stretched). this contributes to in the systemic circulation, the mean pressure (p)-flow (q) plot is well described as a linear (ohmic) relationship. the two points identified (open circles) show a normal cardiac output and a reduced cardiac output, respectively, in the hypertensive condition. at each of these cardiac outputs, it is clear that the ratio of p to q is the same and therefore can be used to easily characterise the resistance of the systemic circulation. (b) in the pulmonary circulation, the plot of mean pressure against flow is curvilinear with an intercept on the pressure axis that is equal to left atrial pressure. the blue curve represents a normal pressure flow curve (healthy lung), while the red curve represents pressure flow curve in the presence of hypoxic pulmonary hypertension. the two points identified (open circles) show a normal cardiac output and a reduced cardiac output, respectively, in the hypertensive condition. at each cardiac output the pulmonary vascular resistance, (ppa-lap)/q, is illustrated as the slope of the straight dashed line. even though the two points are each on the same pressure flow curve, the calculated pulmonary vascular resistance is different at the different cardiac outputs. psa, systemic arterial pressure (mean); ppa, pulmonary arterial pressure (mean); q, cardiac output (flow). a marked elevation in pulmonary vascular resistance, even if the vascular transmural pressure is kept constant [ ] . pulmonary arterial pressure is not only affected by changes in pulmonary vascular resistance but also changes in right ventricular (rv) output. rv output, in turn, is affected by factors that are extrinsic to the lung. it is evident, even from this brief summary, that pulmonary arterial pressure and pulmonary vascular resistance cannot be used as interchangeable measures of the state of pulmonary haemodynamics in patients with ards. for a comprehensive review of this problem of interpreting changes in pulmonary vascular resistance, the reader is referred to the work of vesprille and naeije [ , ] . many of the candidate mechanisms that explain an elevation in pvr in ards have been recently reviewed [ ] . we will highlight the pathophysiology of some of these mechanisms. bradford and dean were among the first to recognise that hypoxia resulted in sustained elevations in pulmonary arterial pressure [ ] . the mechanisms that underlie hypoxic pulmonary vasoconstriction (hpv) are complex and primarily relate to intracellular increases in calcium concentration and rho kinase-mediated sensitisation in pulmonary arterial smooth muscle cells [ ] [ ] [ ] [ ] . hpv causes an increase in pvr to % to % of baseline when healthy volunteers are exposed to hypoxia (po mmhg) [ ] . marshall et al. have shown that when hpv is acutely reduced in ards by the administration of % inspired oxygen, pulmonary arterial pressure was reduced by the order of % to % from its peak [ ] . this may be an underestimate of the extent of hpv in the lung, as it does not take into account the contribution of hpv in non-ventilated lung units. to assess the contribution of non-ventilated lung units to hpv, benzing et al. took a group of patients with severe ards treated by veno-venous extracorporeal lung assist and ventilated them with an fio of . for a period of min prior to taking measurements (thereby minimising hpv in ventilated lung units). they then manipulated the mixed venous partial pressure of oxygen (pvo ) by adjusting the proportion of blood flow diverted through the oxygenator in order to assess hpv in non-ventilated regions. when pvo was high ( . ± . mmhg), the total lung pvr was (± ) dyne.s.cm − .m and increased by . % to (± ) dyne.s.cm − .m when pvo was reduced to low values ( . ± . mmhg) [ ] , clearly demonstrating that hpv in non-ventilated lung units contributes significantly to the increase in pulmonary vascular resistance in ards. in addition to the influence of hpv, disruption of the endothelium in ards results in an alteration in the normal balance of mediators of vasodilation (no, prostacyclin) and vasoconstriction (thromboxane, leukotrienes, endothelin, serotonin, angiotensin ii) favouring vasoconstriction. these factors have been reviewed recently [ , ] . tomashefski et al., in a landmark post-mortem study of patients with ards, found that patients had evidence of microthrombi. nineteen had macrothrombi in the pulmonary arterial and capillary vessels [ ] . they also found endothelial injury in all stages of ards in all cases on both standard histological preparations and electron microscopy. there is now ample evidence supporting the concept of lung injury causing local, as opposed to systemic, coagulation in ards [ , , ] . tissue factor (tf) is released from endothelial cells that have been injured, in response to a variety of proinflammatory stimuli [ ] . tf is a strong activator of the extrinsic clotting cascade. increased activation of procoagulant processes occurs in the lung in ards and does not result from the systemic activation of coagulation (such as is seen in sepsis) [ , ] . animal data suggest that blockade of the tf-factor viia-factor xa complex may reduce the degree of pulmonary hypertension in ards [ ] . levels of protein c, a natural anticoagulant, are also reduced in ards [ ] while levels of plasminogen activator inhibitor- are increased in ards patients, and both are prognostic of increased mortality in ards [ ] . more recently, biomarkers of coagulation and inflammation have been shown to provide good discrimination for the diagnosis of patients with ards [ , ] , and analysis of sars-cov infection in laboratory models has shown that the delicate balance between coagulation and fibrinolysis is shifted towards fibrin deposition during infection leading to ards [ ] . therapies targeting this pulmonary coagulopathy may also have an anti-inflammatory effect and attenuate the severity of ards [ ] . therefore, ards represents a procoagulant, antifibrinolytic phenotype and results in the local formation of microthrombi, which may, in turn, act to increase the pulmonary vascular resistance by the mechanical obstruction of blood flow. fibroproliferation is a characteristic of the late stage of ards, and is present in approximately % of patients who die of this condition [ ] . it is associated with increased mortality, and the presence of fibrosis on thin cut ct scan has been used to predict outcome in ards [ , ] . in a small post-mortem study of the lungs of patients who had died with 'severe respiratory failure' , zapol et al. demonstrated that there is increasing destruction of the capillary bed as ards progresses, which may contribute to elevations in the pvr of the same patients measured ante-mortem [ ] . many mediators have been linked to the fibroproliferative response, but those that have an association with vascular effects include angiotensin ii and vascular endothelial growth factor (vegf) [ ] [ ] [ ] . tomashefski et al. [ ] noted that there was electron microscopy evidence for extensive vascular remodelling in ards. the intermediate phase was characterised by fibrocellular obliteration of the arteries, veins and even lymphatic vessels. in the late stage, vascular remodelling was associated with distorted, tortuous arteries and veins. these tortuous channels were concentrated in regions of dense or irregular fibrosis. the number of capillaries was reduced, and they were often dilated. muscularisation of the arteries was identified in the intermediate phase and was very marked in the late phase. this mechanical disruption of the course of blood vessels is likely to contribute to the sustained elevation in pvr seen in non-survivors. a key difference between normal lungs and injured lungs in ards is the use of mechanical ventilation in the latter, requiring the application of peep and positive inspiratory plateau pressures. when peep is applied to a diseased lung, the change in pvr is determined by the balance between overdistension of lung units and recruitment of areas with previously low numbers of open alveoli. when the number of open alveoli increases following a recruitment manoeuvre and application of high peep, then pvr may even fall in keeping with whittenberger's-u shaped relationship between pulmonary vascular resistance and lung volume. any increase in ventilated alveolar area may also reduce hpv. canada et al., found that the pulmonary vascular resistance index (pvri) was lowest at cm h o in the normal lung but cm h o had to be applied to the injured lung in order to achieve minimal pvri [ ] . above 'optimal peep' levels, the pvr increased, presumably due to compression of intra-alveolar capillaries by the increased airway pressure resulting in an increase in zone and characteristics [ , ] . there are very few studies which have measured pulmonary vascular resistance in ards patients ventilated with lower tidal volumes, perhaps due to the reduction in the use of the pulmonary artery catheter just as lung-protective ventilation was gaining widespread acceptance [ ] . limitation of plateau pressures has, however, been shown to be associated with lower rates of right ventricular failure than in historical studies [ , ] . the application of higher tidal volume to the patients in these studies was associated with a significant increase in right ventricular afterload [ ] . there is currently no evidence to suggest that one mode of ventilation has more or less effect than any other mode on pulmonary vascular haemodynamics. any effect of the mode of ventilation on pvr is likely to be related to the amount of peep and plateau pressure that is applied. why do the studies of pulmonary haemodynamics report inconsistent relationships with mortality? as is apparent, pvr is directly influenced by factors that are intrinsic to the lung and can be increased by the pathophysiological insults that occur in ards. in contrast, pap is affected both by factors extrinsic to the lung (e.g. rv output preload and contractility) and by factors intrinsic to the lung (pvr). in clinical practice, there is considerable variability in the preload of patients with ards. both volume loading and venous tone have a considerable influence on the amount of venous return reaching the heart. the presence of sepsis and the use of vasopressors will both affect venous tone. likewise, raised intra-thoracic pressure can have a compressive effect on the intra-thoracic veins, including the superior and inferior venae cavae [ ] and limit venous return in patients with ards. sepsis-induced cardiac dysfunction may result in rv impairment in as many as % of patients [ ] . the studies in table have reached different conclusions about the significance of pap and pvr and their relationship to outcome in ards. what might account for these differences? all except one of the studies quoted are observational in nature and did not employ standard patient management protocols. the studies were not designed to answer specific questions about the nature of pulmonary haemodynamics in ards, and the data were drawn from patients who were managed differently in terms of mechanical ventilation (mode and pressures applied), fluid status and vasopressor use, all of which adds to the statistical noise when trying to draw useful conclusions. bull et al.'s data came from patients who all had a standardised approach to ventilator management (in particular the use of low tidal volume ventilation), pulmonary artery catheter data acquisition as well as fluid management. bull et al.'s study, the largest in the modern era of 'protective ventilation' found no association between pap and outcome but showed a highly significant and independent link between two indices of pulmonary vascular dysfunction (mpap-paop and pvri) and mortality. pvr is primarily affected by factors that are intrinsic to the lung, while pap is influenced by both pvr and rv preload and contractility. when the variability in management was controlled for (as in bull et al.'s study), the measured pvr was more likely to have reflected the vascular changes induced by the disease process in ards. this is because the protocol standardised many of the extrinsic factors (airway pressure, tidal volume, fluid loading) that can influence pa pressure independently of changes in pulmonary vascular resistance. importantly, in this wellcontrolled study, indices of elevated pulmonary vascular resistance were found to independently predict greater mortality in ards. this highly significant association between mortality and measures of pulmonary vascular resistance, in a carefully controlled study, raises the question as to whether pvd directly causes increased mortality or is it associated with mortality. there are two potential mechanisms by which an elevation in pvr could cause mortality in ards. either it results in right ventricular failure, with subsequent multi-organ dysfunction or it exacerbates the acute lung injury directly. the right ventricle is more sensitive to acute increases in its afterload than the left ventricle. we know from studies of major pulmonary embolism, that a normal right ventricle cannot acutely generate pulmonary pressures greater than mmhg (mean) and quickly fails in this clinical context [ ] . is the same true for patients with ards? sustained pulmonary hypertension may result in right ventricular failure (rvf) in ards patients [ ] . over the years, the incidence of right ventricular dysfunction (rvd) has declined as improvements in mechanical ventilation have been adopted and lessened the intrathoracic airway pressure in patients with ards [ , ] , but rvd is variably defined and diagnosed among studies which makes comparison difficult. clinically, right ventricular failure has no agreed definition, but criteria (using pulmonary artery catheter data) include pulmonary hypertension associated with an rv cardiac index < . l min − m − and a right atrial pressure > mmhg [ ] . using these criteria, osman et al. found an incidence of right ventricular failure of . % in patients with ards [ ] . the presence of rvf was not associated with death. in bull et al.'s analysis of patients with ards, they reported an incidence of right ventricular failure (rvf) of % (using monchi's definition of right atrial pressure > pulmonary artery occlusion pressure [ , ] ); rvf was not predictive of mortality. the presence of rvf can also be inferred using echocardiographic criteria. acute cor pulmonale (acp) has been defined as the presence of rv dilation (ratio of rv end-diastolic area to left ventricle end-diastolic area > . ) in association with dyskinesia of the interventicular septum in response to an increased afterload [ ] . jardin et al. originally described the two-dimensional echo characteristics in a group of patients with acute respiratory failure, showing that the right ventricular enddiastolic area increased as the pvri (measured using a pac) increased and rv stroke volume declined [ ] . vieillard-baron et al. have demonstrated an incidence of echocardiographic cor pulmonale of % in a study of patients with ards [ , ] . however, acp was found to be reversible in those patients whose ards resolved, and it did not have a negative prognostic significance. similar results were found by cepkova in a study of patients with acute lung injury [ ] . in a retrospective analysis of patients with ards admitted to their unit since , jardin's group found a correlation between increasing levels of plateau pressure and the incidence of acute cor pulmonale [ ] . as measured plateau pressure increased, the incidence of acp rose up to % with plateau pressures of > cm h o. while they also noted an association between the presence of acp and mortality in the overall group, this did not hold true when the airway pressure was aggressively limited, in line with current practice [ ] . vieillard-baron's group [ , , , , ] have suggested that the increases in rv afterload due to elevations in peep and plateau pressure, as well the underlying lung injury, result in rv dysfunction that is sufficient to increase mortality. this reflects what we know of the pathophysiology of pulmonary embolism, but the evidence is not as definitive in ards. the presence of acp has not been consistently demonstrated to be associated with excess mortality in ards in the modern era of protective ventilation. perhaps this is because the authors modified their approach to mechanical ventilation in these studies when acp was recognised, in order to limit the distension of the right ventricle by reducing the airway pressures (peep and plateau) and putting the patient in a prone position [ , ] . recent echocardiographic derived data on right ventricular dysfunction from boissier et al. [ ] suggest that even when tidal volume and plateau pressure are limited in line with best practice, the incidence of acp in ards is still % and is independently associated with mortality in spite of greater use of prone positioning and nitric oxide. lheritier et al. [ ] found a similar incidence of acp ( . %) in moderate to severe ards patients ventilated with a lung protective strategy, but they could not find an association between the presence of acp and outcome. in both studies, the groups with acp had a higher use of nitric oxide and prone positioning compared to those without acp. it is unclear what accounts for the different findings in these studies. the relationship between acp/rvd and outcome in ards is therefore unclear, and it remains to be determined. it is worth asking the question as to whether there is a plausible mechanistic basis that would allow pulmonary vascular dysfunction to worsen ards. high-altitude pulmonary oedema (hape) is a condition that occurs in previously healthy individuals within to days after rapid ascent above altitudes of , to , m [ , ] . while it is not a form of ards, it is a severe form of non-cardiogenic pulmonary oedema, which can develop in susceptible individuals ( % to % of the normal population) in the presence of hypoxia alone [ ] . individuals who develop hape have an increased degree of hpv compared to unaffected members of the population. pulmonary artery pressure at an altitude of , m is about % to % higher in individuals who are prone to hape compared with non-susceptible controls, and this higher pressure precedes oedema formation [ ] . the increase in hpv can also be demonstrated at low altitude in susceptible individuals exposed to a brief hypoxic challenge [ , ] . lowering pulmonary artery pressure during the ascent to high altitude can prevent hape. a non-specific pulmonary vasodilator (nifedipine) [ ] or the phosphodiesterase- -inhibitor tadalafil [ ] reduced the prevalence of pulmonary oedema in hape-susceptible individuals after rapid ascent to , m from % to about %. this suggests that excessive hpv may contribute to the development of acute oedema, possibly by redistributing pulmonary blood flow away from areas with high degrees of hpv to other sections of the lung, with resultant hyper-perfusion, endothelial injury and capillary leak. this causes a secondary inflammation which is clinically indistinguishable from ards [ ] . the finding that a subset of the population is prone to the development of non-cardiogenic pulmonary oedema, as a result of exposure to hypoxia alone, is of relevance to our understanding of ards. ards is characterised by heterogeneous areas of alveolar hypoxia and inappropriate vascular responses to these areas of hypoxia may partially explain the finding that individuals with pulmonary vascular dysfunction have worse outcomes in ards. there is, as of yet, no evidence to support this hypothesis in the general population who present with ards. is pvd a marker of the severity of ards? as patients recover from ards, there is resolution of the pulmonary vascular dysfunction. many of the mechanisms of pvd in ards (the release of multiple vasoactive mediators, vascular remodelling and the formation of vasoocclusive microthrombi) are caused by the disruption of the normal endothelial-inflammation-coagulation pathways. pvd may be a good summative index of vascular damage from these mechanisms. nuckton et al. has previously reported that an increased dead space fraction was associated with increased mortality in ards [ ] , which they postulated might be due to injury to the pulmonary capillaries from inflammation and thrombosis and obstruction of pulmonary blood flow in the extraalveolar pulmonary circulation. there is evidence that extra-pulmonary organ dysfunction in ards is caused by the systemic inflammatory response, which in turn is driven by the initiating pulmonary injury [ ] . if pvd is primarily a downstream result of the activation of the inflammatory-coagulation cascade in the lung, then, the reason it is associated with mortality in ards may be because it reflects the severity of the underlying inflammatory process. this hypothesis may also help to explain why pvd is associated with mortality in wellcontrolled studies of patients with ards whereas right ventricular dysfunction has not been consistently shown to be associated with mortality. ards studies are rarely adequately powered to look at mortality as they do not recruit sufficient numbers of patients to be able to draw valid conclusions. using pvd as an index of disease severity might allow researchers an additional way to stratify the severity of lung injury and to test the efficacy of new treatments for ards by measuring the change in pvd, which is known to improve as the patient recovers from lung injury. in order to develop new treatments for ards, we need better methods for examining their efficacy. using pvd as an endpoint might improve the predictive value of phase ii trials prior to embarking on full scale clinical studies of new treatments. assessment of pulmonary vascular resistance may be possible using non-invasive echocardiographic technology [ ] which would increase the applicability of this approach and may be worth pursuing. pulmonary vascular dysfunction is an independent predictor of mortality in ards. an examination of the physiology of pulmonary haemodynamics in ards helps to explain why it may be a clearer mortality signal, when compared to the inconsistent link between mortality and pulmonary arterial pressure or right ventricular dysfunction. further study is needed to determine precisely the dominant pathways involved in causing pvd in ards. this is an area of research that may yet lead to greater understanding of the complex interplay between the pulmonary circulation, endothelial dysfunction and activation of the inflammatory-coagulation cascades that underlie ards. abbreviations acp: acute cor pulmonale; ards: acute respiratory distress syndrome; co: cardiac output; hpv: hypoxic pulmonary vasoconstriction; lap: left atrial pressure; mpap: mean pulmonary arterial pressure; no: nitric oxide; p:f: ratio of partial pressure of oxygen to fraction of inspired oxygen; pplat: plateau pressure; pac: pulmonary artery catheter; padp: pulmonary arterial diastolic pressure; paop: pulmonary arterial occlusion pressure; pap: pulmonary arterial pressure; pasp: pulmonary arterial systolic pressure; peep: positive end-expiratory pressure; pvd: pulmonary vascular dysfunction; pvr: pulmonary vascular resistance; rv: right ventricle; rvd: right ventricular dysfunction; rvf: right ventricular failure; tpg: transpulmonary gradient. the authors declare that they have no competing interests. authors' contributions dr was responsible for writing, editing and reviewing the majority of the manuscript. sf wrote and reviewed the section on high-altitude pulmonary oedema. pmcl was responsible for the concept for the review, editing and final review of the manuscript. all authors read and approved the final manuscript. the acute respiratory distress syndrome acute respiratory distress syndrome network (ardsnet): ventilation with lower tidal volumes as compared with 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and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial adult respiratory distress syndrome secondary to high altitude pulmonary edema pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome activation and regulation of systemic inflammation in ards: rationale for prolonged glucocorticoid therapy echocardiography based estimation of pulmonary vascular resistance in patients with pulmonary hypertension: a simultaneous doppler echocardiography and cardiac catheterization study pulmonary vascular dysfunction in ards. annals of intensive care convenient online submission rigorous peer review immediate publication on acceptance open access: articles freely available online high visibility within the fi eld retaining the copyright to your article submit your next manuscript at springeropen.com key: cord- -mhe q ce authors: sanaie, sarvin; mirzalou, negin; shadvar, kamran; golzari, samad e. j.; soleimanpour, hassan; shamekh, ali; bettampadi, deepti; safiri, saeid; mahmoodpoor, ata title: a comparison of nasogastric tube insertion by sort maneuver (sniffing position, ngt orientation, contralateral rotation, and twisting movement) versus neck flexion lateral pressure in critically ill patients admitted to icu: a prospective randomized clinical trial date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: mhe q ce background: although many techniques have been introduced to facilitate nasogastric tube (ngt) insertion using anatomic landmarks and a group of devices, there is a lack of general consensus regarding a standard method. the current study purposed to investigate if sort maneuver (sniffing position, ngt orientation, contralateral rotation, and twisting movement) increases the success rate of ngt correct placement versus neck flexion lateral pressure (nflp) method. methods: a randomized controlled trial study was conducted in two university affiliated intensive care units (tertiary referral center). three hundred and ninety-six critically ill patients older than years of age were randomly divided into sort (n = ) and nflp (n = ) groups. the technique was classified as “failed” after the third unsuccessful attempt. patient characteristics, success rate for the first attempt, time required for the successful first attempt and overall successful insertion time, various complications including kinking, coiling and bleeding and ease of insertion were noted as main outcomes measured. results: ease of insertion was significantly better in the sort group compared to the nflp group (p < . ). the number of failed attempts was significantly higher in the nflp group ( . %) vs the sort group ( . %) (p = . ). the pattern of complications was not different between two study groups (p = . ). the odds of stage ii (odds ratio (or) = . ; % confidence interval (ci) . to . ), stage iii (or = . ; % ci . to . )) and stage iv (or = . ; % ci . to . ) ease of insertion were much higher in nflp compared to sort group, after adjusting for age and body mass index (bmi). the odds of failure was not significantly different in nflp group compared to sort group (or = . ; % ci . to . ), after adjusting for age and bmi. conclusions: sort technique may be considered as a promising method for successful ngt insertions in critically ill patients. however, more trials are needed to confirm the results of this study. the decision must account for individual patient and clinical factors and the operator’s experience and preference. trial registration: the study was registered at government registry of clinical trials in iran (http://www.irct.ir) (number: irct n , march ) nasogastric tube (ngt) insertion is one of the most commonly performed interventions in critically ill patients [ ] . but its insertion in these patients is challenging as they cannot swallow ngt, which results in ngt kinking and coiling in the oral cavity [ ] . furthermore, its flexible nature and presence of an inflated endotracheal tube cuff can make its placement impossible especially during the first attempt [ ] . although its insertion appears simple, due to invasive nature of this procedure, repeated attempts may result in complications like aspiration, intracranial placement, nasal bleeding, esophageal perforation, hydrothorax and empyema [ ] . the most common sites of misplacement are piriform sinus, arytenoid cartilage, esophagus and lungs [ ] [ ] [ ] . the routine way for ngt insertion is the blind technique with the patient's neck in neutral position and a lateral neck pressure head flexion. there are several methods which help the insertion of ngt, including reverse sellick's maneuver, frozen ngt, with use of endoscope or forceps, stylet, split endotracheal tube and angiography catheter/esophageal guidewire assisted techniques [ , [ ] [ ] [ ] [ ] . (the list of mentioned methods is fully shown in appendix table .) considering feasibility and cost effectiveness, there is growing interest in ngt insertion techniques that are not device-based. it has been noted that most difficulties in ngt insertion are due to anatomic reasons, so to maximize the insertion efficiency and minimize iatrogenic complications, the anatomical variation during ngt insertion must be considered. najafi introduced a new method named sort maneuver for ngt placement [ ] . sort is a mnemonic word for the four main steps of the maneuver, namely: sniffing position, ngt orientation, contralateral rotation, and twisting movement [ ] . he recommended that the manoeuver could also be of assistance in trans-esophageal echocardiography probe insertion. existence of different methods with variable reported success rates indicates that the quest for the best method is still on. the present study was carried out to compare ngt insertion by sort maneuver with neck flexion lateral pressure (nflp) in critically ill patients admitted to icu. this study was a single-blind randomized clinical trial and was registered with the government registry of clinical trials in iran (http://www.irct.ir) under trial number irct n . a partial waiver for health insurance portability and accountability act (hipaa) was obtained to allow the investigative team to screen the patients' charts for their eligibility. an informed consent was obtained from the patients if their cognition level was intact or from the next-of-kin/healthcare proxy if the mentation was suppressed. five hundred and fifty-one patients who were admitted into two university affiliated icus and needed ngt placement were enrolled in this randomized clinical trial. the study took place at the mixed medical/surgical icus of the two main teaching hospitals ( inpatient bed) and major trauma centers in tabriz, iran from april to jan . flow diagram of the study is shown in fig. . all critically ill patients older than years of age and without skull base fracture, coagulopathy, nasopharynx and esophageal pathology, history of head and neck radiotherapy and neck trauma who needed ngt placement were enrolled in the study. patients' refusal to participate in the study was considered as the exclusion criteria. patients were randomly divided into two groups using a balanced block randomization by the research pharmacy team; group nflp in which ngt was inserted for all patients with standard method (nflp) and group sort in which ngt was inserted through sort maneuver. a fr. , -cm ng tube was used in all cases, and the insertion was performed by two critical care registered nurses who were experienced in ng tube insertion in critically ill patients by these two methods. as sort method is a new one and not routine in our icus, the nurses who were supposed to perform it had to complete the education course for sort method. only two nurses performed the ngt insertion by sort method in this study in order to decrease interpersonal variations. these two nurses were educated to perform ngt insertion with sort maneuver for days prior to the start of our trial. they performed almost to ngt insertion with sort maneuver. we assessed the success/failure rate for them which did not have any difference between the two nurses. the distal end of the ng tube was lubricated in all cases and passed through the larger nostril to the nasopharynx. the tube was then advanced into the posterior oropharynx according to the selected technique. in group nflp, a lubricated ngt was inserted through the selected nostril to a depth of cm. lateral neck pressure was applied at the same side as that of the selected nostril with the neck flexed and the ngt was advanced to the targeted point. in group sort, after the patient was placed in sniffing position, ngt was oriented from the nose to the esophagus entrance considering anatomical landmarks. the position of ngt tip was changed by back and forth and rotational movements until it found its way through the esophagus without any resistance. if any resistance occurred, the procedure was stopped. sliding distal end of ngt on the posterior wall of oropharynx into the esophagus by the tip of the index finger is sometimes helpful for an accurate orientation. after that, we rotated the head to the contralateral side of ngt entrance. then, the tip of ngt was directed deep into the esophagus by twisting movements to reduce resistance. we performed external pressure on the area of piriform sinus if the initial maneuver failed. we confirmed the correct place of ngt with epigastric auscultation, aspiration of gastric contents and finally a chest x-ray for reconfirmation. if the first attempt was failed, ngt was withdrawn and fully cleaned and then reinserted in the same nostril. after the third attempt, the technique was considered as "failed" and ngt insertion was guided by laryngoscope and magill forceps to advance the ngt under direct vision. the ngt length was estimated with measuring the distance from the xiphoid process to the earlobe via the nose [ ] . primary endpoint of our study was success rate for ngt insertion in each group. the secondary end points were complication and ease of insertion in each group. patient characteristics and following data were noted for all patients: success rate at the first attempt, the second attempt and overall for each group, time required for fig. flow diagram of the study successful first attempt and overall successful insertion time, various complications including kinking, knotting and bleeding. we also reported other rare complications like insertion to cranium, pneumothorax and chylothorax if they occurred. we evaluated the ease of insertion with a -grade score as following: first grade as successful insertion in less than s and in the first attempt, second grade as successful insertion in the first attempt with more than s or in the second attempt with less than s, third grade as successful insertion in the nd attempt with more than s or in three attempts, and fourth grade as failed insertion. the sample size was calculated based on the pilot study as there was no similar previous study. a sample size of per group was calculated to identify at least a % difference in proportions of failure from the baseline % proportion and to fulfill a minimum statistical power of % and % confidence level. additional sample size was considered for the multivariable analyses. finally, and patients were assigned into the nflp and sort groups, respectively. at the first stage, the distributions of quantitative variables were examined using the kolmogorov-smirnov test and histogram plots. the quantitative variables with and without normal distribution were reported as mean ± standard deviation and median (interquartile range), respectively. the qualitative variables were reported as frequency (%). normally distributed variables were compared between two groups using independent samples t test and those without normal distribution were compared with mann-whitney u test. in addition, chi-squared and fisher's exact tests were used to compare the qualitative variable between two groups. the study variables were compared between the nflp and sort groups and those with p < . were further studied whether to be included as confounding variables. finally, binary and multinomial logistic regressions were applied to examine the association of categorical and binary outcomes with ngt insertion techniques, respectively, after adjusting for confounders. p < . was considered statistically significant. all analyses were done by spss software version (spss inc., chicago, il, usa) and stata version (stata corporation, college station, tx, usa). three hundred and ninety-six critically ill patients who required ngt insertion were enrolled in this study. group nflp consisted of patients and group sort consisted of patients. flow diagram of the study is shown in fig. . patients in two groups did not have significant differences regarding sex (p = . ), but the median of age was significantly higher in nflp than sort group (p = . ). patients in two groups did not have a significant difference in weight (p = . ), but had a significant difference regarding body mass index (p = . ). demographic characteristics of patients are shown in table . before comparing the outcomes of interest between two study groups, the mallampati score of groups were compared and it was found that the difference between two groups was not statistically different (p = . ). however, it was found that the pattern of ease of insertion stages were different between the two studied groups (p < . ). overall, successful intubation was significantly more in sort group compared to nflp (p = . ). furthermore, successful insertion in less than s and in the first attempt (stage i) was more common in the sort group than nflp group ( . % vs. . %). also, successful insertion in the first attempt with more than s, or in the second attempts with less than s (stage ii) was fewer in sort than nflp groups ( . % vs. . %). in addition, successful insertion in the second attempts with more than s, or in three attempts (stage iii) and failure (stage iv) were less common in sort group than nflp group ( . % vs. . % and . % vs. . %), respectively. finally, failed ngt insertion happened in % and . % of patients in sort and nflp groups, respectively (p = . ) ( table ). the pattern of complications such as bleeding, kinking, and coiling or combination of them were not different between study groups (p = . ). there was not any case of rare complications like insertion to cranium, pneumothorax, chylothorax, etc. after adjusting for high body mass index and age, the odds of unfavorable outcomes such as stage ii (or = . ; % ci . to . ), stage iii (or = . ; % ci . to . ) and stage iv (or = . ; % ci . to . ) ease of insertion was much higher in nflp than sort group, compared to the reference group (stage i) (table ) . moreover, after adjusting for high body mass index, the odds of failure in the nflp was higher, but not statistically significant than sort group (or = . ; % ci . to . ). the results of this clinical trial shows that sort maneuver, as a simple technique, significantly increases the success rate of the first attempt insertion, overall success rate, and ease of ngt insertion, and also decreases the time required for correct ngt placement in critically ill patients admitted to icu. although the odds of failure was not statistically different between two groups after adjusting for high body mass index, it was an expected issue as the number of failed cases in two groups, especially in sort group, was very low and power reduction was not avoidable in the multivariable model. so, this point needs to be interpreted with caution and we should not ignore the lower odds of failure in the sort group due to the insufficient power of multivariable model. the insertion of ngt can be difficult even for experienced physicians, as the routine way for its insertion is the blind technique. variation of patients' functional anatomy, whether physiologic or pathologic, can furthermore increase the difficulty of ngt insertion. there are many trials that have used glidescope or macintosh laryngoscope with the assisted magill forceps [ , , ] . but the limited space provided by the laryngoscope or the glidescope blade for the manipulation of magill forceps is a drawback of this method which can decrease the success rate or may result in increased complications. some authors recommended the ipsilateral compression of the neck at the level of the lateral border of the thyrohyoid membrane to transiently collapse the ipsilateral piriform sinus and slightly move the arytenoid cartilage which results in easier insertion of ngt via lateral or posterior hypopharynx [ ] . another technique table comparing the outcomes of interest between the study groups nflp: neck flexion lateral pressure; sort: sniffing position, ngt orientation, contralateral rotation, and twisting movement ease of insertion: i: successful insertion in less than s and in first attempt ii: successful insertion in st attempt with more than s, or in nd attempts with less than s iii: successful insertion in nd attempts with more than s, or in attempts to overcome the difficulties of blind ngt insertion is considering patients' anatomical factors. piriform sinus and arytenoid cartilages are the most common places in which ngt is usually lodged [ ] . najafi introduced a new technique named sort maneuver for facilitation of ngt placement in anesthetized patients which seems as a suitable approach to solve the mentioned problems [ ] . each component of this maneuver overcomes a problem during ngt insertion. sniffing position thrusts the arytenoid cartilage away from esophageal entrance. contralateral rotation of head blunts the ipsilateral piriform sinus malposition while orientation changes the anterior curve of ngt tip to posterior, facing the esophagus. twisting is for applying back and forth movement to ngt tip in order to reduce resistance during deep insertion until it finds its way through esophagus. this is the first study that evaluates the effect of sort maneuver in critically ill patients and our results show that this technique can decrease the failed attempts, the number of attempts and the time required for correct placement of ngt. kayro et al. showed that using a -cm-high pillow was the best way to insert a ngt, but ipsilateral head rotation did not contribute to the procedure [ ] . ngt insertion without rotation generally causes impingement of the tip of the ngt on the posterior aspect of the tongue which usually leads to intraoral coiling. the tip of the ngt is always directed anteriorly, so this can also potentially cause misplacement of the ngt into trachea. with sort maneuver, the tip is always faced posteriorly, hence the tube always advances with the posterior esophageal wall. as a result, it reduces the chances of tube misplacement which is similar to some previous reports [ ] . kinking and coiling of the ngt are the most common complications in previous reports [ ] , which is consistent with our results. nowadays, combined techniques have been considered for ngt placement especially in unconscious patients. gatack et al. performed a study evaluating the combined facilitating effects of reverse sellick's maneuver and neck flexion [ ] . in another study, kirtania et al. showed that esophageal guide wire assisted insertion while maintaining manual forward laryngeal displacement resulted in more successful attempts compared to the technique of head flexion while maintaining lateral neck pressure [ ] . both techniques, like ours, showed the positive results with combining different techniques. one of the most important points regarding correct ngt placement is to develop interventions based on primary caregivers' knowledge and skills with regard to ngt insertion techniques [ ] . this is one of the strengths of our trial as we provided training for our nurses and physicians before starting this trial which may affect the results in the way that produces such a high success rate. this is the first clinical trial regarding efficacy of sort maneuver in the insertion of ngt in humans and for generalizing the results, we need more trials. thence, this method may be used as an ideal and simple method for ngt insertion in different situations like tee as mentioned by najafi et al. [ ] . this study has some limitations. first, this study is not a double-blinded study. second, we did not enroll children or patients who had not been stabilized. however, the technique should be tested in patients with high risk of ngt insertion difficulty. although all ngt were inserted by two experienced nurses causing a decrease in the inter-personal variation, we should try this method with different nurses on different populations to generalize the results of this study. ngt is usually impacted at arytenoid cartilage level and also, inflated balloon of tracheal tube can cause obstruction of the ngt in intubated patients, especially in conditions where cuff pressure measurement is not common. additionally, cerebral protection is very important in critically ill patients and this technique does not require the use the laryngoscope (that could increase intracranial pressure further). our four-in-one technique also helps in decreasing the aspiration and ventilatorassociated pneumonia chances as this technique does not require deflation of endotracheal tube cuff. we believe that sort maneuver is a simple technique and does not need any skill for its insertion, but we need more trials to confirm this hypothesis in unskilled inserters. in future, larger studies involving those populations may consolidate the suitability of these modified techniques and may establish the superiority of any of them in the difficult or special situations. the sort maneuver has a high success rate for ngt insertion and increases the ease of insertion. hence, this method may be considered in critically ill patients, but still there is no consensus regarding a standard approach, and the decision must account for every patient individually and on the basis of clinical factors and the operator's experience and preference. verifying the placement of nasogastric tubes at an emergency center: comparison of ultrasound with chest radiograph nasogastric tube insertion in anesthetized and intubated patients: a new and reliable method nasogastric tube insertion in anesthetized intubated patients undergoing laparoscopic hysterectomies: a comparative study of three techniques thoracic complications of nasogastric tube: review of safe practice nasogastric tube insertion using different techniques in anesthetized patients: a prospective, randomized study another method to assist nasogastric tube insertion insertion of a nasogastric tube using a modified ureteric guide wire esophageal guidewire-assisted nasogastric tube insertion in anesthetized and intubated patients: a prospective randomized controlled study a new technique to insert nasogastric tube in an unconscious intubated patient a randomized, clinical trial of frozen versus standard nasogastric tube placement nasogastric tube insertion in anaesthetized patients: a comprehensive review nasogastric tube insertion easily done: the sort maneuver sort maneuver for nasogastric tube insertion inserting a nasogastric tube: you'll do this to remove gastric contents, administer medications and feedings, and more here's what you should know comparison of different methods of nasogastric tube insertion in anesthetized and intubated patients oro-and nasogastric tube passage in intubated patients fiberoptic description of where they go at the laryngeal level and how to make them enter the esophagus a study on insertion of a nasogastric tube in intubated patients easier nasogastric tube insertion a comparison of nasogastric tube insertion techniques without using other instruments in anesthetized and intubated patients the effects of systematic educational interventions about nasogastric tube feeding on caregivers' knowledge and skills and the incidence of feeding complications publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we would like to thank mrs. sanaz jalali for her assistance with the study. sars and am were responsible for conception and design of the study, data acquisition, and drafting/editing of the manuscript; saes and db were responsible for a substantial portion of the data analysis, manuscript drafting and revision; nm and as made a substantial contribution to the study design, data acquisition and manuscript drafting; ks and hs made a substantial contribution to the study design, data acquisition; sejg was responsible for conception and design of the study, and drafting of the manuscript. all authors read and approved the final manuscript. the present work was supported by tabriz university of medical sciences. the datasets used and/or analyzed in the present study are available from the corresponding author on reasonable request. the study protocol and the informed consent were reviewed and approved by the institutional review committee on health research ethics at tabriz university of medical sciences for its merit (study protocol approval date: . . . ethics committee reference number: ir.tbzmed.rec. . ). not applicable. the authors declare that they have no competing interests. see table . key: cord- -mbqncen authors: de pascale, gennaro; lisi, lucia; ciotti, gabriella maria pia; vallecoccia, maria sole; cutuli, salvatore lucio; cascarano, laura; gelormini, camilla; bello, giuseppe; montini, luca; carelli, simone; di gravio, valentina; tumbarello, mario; sanguinetti, maurizio; navarra, pierluigi; antonelli, massimo title: pharmacokinetics of high-dose tigecycline in critically ill patients with severe infections date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: mbqncen background: in critically ill patients, the use of high tigecycline dosages (hd tgc) ( mg/day) has been recently increasing but few pharmacokinetic/pharmacodynamic (pk/pd) data are available. we designed a prospective observational study to describe the pharmacokinetic/pharmacodynamic (pk/pd) profile of hd tgc in a cohort of critically ill patients with severe infections. results: this was a single centre, prospective, observational study that was conducted in the -bed mixed icu of a -bed teaching hospital in rome, italy. in all patients admitted to the icu between and , who received tgc ( mg loading dose, then mg q ) for the treatment of documented infections, serial blood samples were collected to measure steady-state tgc concentrations. moreover, epithelial lining fluid (elf) concentrations were determined in patients with nosocomial pneumonia. amongst the non-obese patients included, had a treatment failure, whilst the other subjects successfully eradicated the infection. there were no between-group differences in terms of demographic aspects and main comorbidities. in nosocomial pneumonia, for a target auc( - )/mic of . , % of the patients would be successfully treated in presence of . mcg/ml mic value and all the patients obtained the pk target with mic ≤ . mcg/ml. in intra-abdominal infections (iai), for a target auc( - )/mic of . , at least % of the patients would be adequately treated against bacteria with mic ≤ . mcg/ml. finally, in skin and soft-tissue infections (ssti), for a target auc( - )/mic of . only % of the patients obtained the pk target at mic values of . mcg/ml and less than % were adequately treated against germs with mic value ≥ mcg/ml. hd tgc showed a relevant pulmonary penetration with a median and iqr elf/plasma ratio (%) of . [ . – . ]. conclusions: the use of hd tgc is associated with satisfactory plasmatic and pulmonary concentrations for the treatment of severe infections due to fully susceptible bacteria (mic < . mcg/ml). even higher dosages and combination strategies may be suggested in presence of difficult to treat pathogens, especially in case of ssti and iai. β-lactamase (esbl)/carbapenem-producing enterobacterales and extensively drug-resistant (xdr) acinetobacter baumannii are susceptible to tgc [ ] [ ] [ ] . tgc is currently approved by the u.s. food and drug administration (fda) for complicated skin and skinstructure infections, complicated intra-abdominal infections, community-acquired pneumonia with an initial dose of mg, followed by mg every h. nevertheless, due to an increased risk of death compared to other antimicrobials, its use has recently been restricted in situations when alternative treatments are not suitable ( [ ] , https ://www.fda.gov/drugs /drug-safet y-and-avail abili ty/ fda-drug-safet ycomm unica tion-fda-warns -incre asedrisk-death -iv-antib acter ial-tygac il-tigec yclin e). however, the alarming increase in antimicrobial resistance amongst the nosocomial pathogens is leading the clinicians to consider the use of tgc as an important therapy in the management of difficult to treat infection, particularly in critically ill patients. this is also supported by recent studies suggesting that previous failures of tgc therapy in critically ill patients were likely due to a drug underdosage [ , ] and that standard doses provide serum concentrations that are below the minimum-inhibitory concentrations (mics) of most mdr pathogens. moreover, it has been reported an increased effectiveness of high-dose tgc (hd tgc) regimen to improve the clinical outcome, without safety issues [ ] [ ] [ ] [ ] . therefore, we designed this prospective observational study to describe the pharmacokinetic/pharmacodynamic (pk/pd) profile of hd tgc in a cohort of critically ill patients with severe infections. this was a prospective, observational study that was performed between and in the -bed icu of a -bed teaching hospital in rome, italy. the protocol was approved by the catholic university's ethical committee (approval number prot.sf / ). written informed consent was obtained from the patients' legally authorized representative. critically ill adult patients were considered eligible for the study when the attending physician prescribed tgc as empirical treatment (within h from microbiological sampling) of a possible mdr infection, or as targeted therapy based on definitive results, in the absence of any exclusion criteria: known tgc allergy, creatinine clearance less than ml/min (calculated according to the cocrockft-gault formula) apart from those ones who were anuric and on continuous renal replacement therapy (crrt), hyperbilirubinemia (bilirubin level higher than mg/dl), severe hepatic failure (child-pugh c), little chance of survival as defined by the simplified acute physiology (saps ) score > , concomitant treatment with other drugs that can potentially interfere with tgc (i.e., rifampin and cyclosporine). patient without microbiologically confirmed infection were not excluded. tgc was administered intravenously at loading dose (ld) of mg over -min, followed by mg over -min bid. on day after the commencement of the hd tgc, at steady state, pharmacokinetic analyses of the study group were performed. clinical and demographic data were recorded upon enrolment. safety and adverse events were determined through the observed biochemical abnormalities, documented according to the department of health and human services-common terminology criteria for adverse events (dhhs-ctcae v. . ) classification [ ] . clinical cure was defined as the complete resolution of all signs and symptoms of the infection by the end of tgc therapy. in case of ventilator-associated pneumonia (vap), improvement or lack of progression of all abnormalities on chest radiographs was also required [ ] . otherwise, the outcome was classified as treatment failure. clinical outcomes were independently evaluated by two physicians (gdp, msv) when judgments were discordant (two cases), the reviewers reassessed the data and reached a consensus decision. the quality of source control was considered adequate when it included drainage of infected fluid collections, debridement of infected solid tissue, removal of devices/foreign bodies, and definitive measures to correct anatomic derangements resulting in on-going microbial contamination and to restore optimal function within h after diagnosis [ ] . although tgc concentration-time profiles are stable dose just on day , blood samples were collected after the seventh dose (on day of treatment) at t (immediately before the initiation of the infusion) and , . , , , , , , and after the start of infusion. according to patients' respiratory status, one mini-bronchoalveolar lavage (bal) ( ml sterile . % saline solution was blindly instilled through a telescopic catheter and immediately aspirated in a trap) was performed on day , in case of suspected hap. stock solution of tgc and the internal standard (is), propranolol hydrochloride, were prepared by dissolving accurately weighed amounts of each compound in meoh to obtain a final concentration of . mcg/ml. calibration standards were prepared by diluting stock solutions of tgc in drug-free human plasma to yield tgc concentrations of , , , , . , . , . , . , . and . ng/ml. tigecycline liquid/liquid extraction from plasma samples (see additional file ). tigecycline solid-phase extraction from bal samples (see additional file ). chromatographic and mass-spectrometric conditions (see additional file ) urea levels were detected by the quantichrom urea assay kit (bioassay system, hayward, ca, usa), which was used according to the manufacturer's instructions. a one-compartment model with first-order elimination determined pharmacokinetic parameters. the - h area under the time-concentration curve (auc - ) was determined by the linear trapezoidal rule. tgc auc - was calculated as auc - x . tgc maximum and minimum concentrations (c max , c min ) were directly obtained from observed peak and trough concentrations. epithelial lining fluid (elf) tigecycline (tgc elf ) concentration was calculated from bal concentration (tgc bal ) using urea as dilution marker: tgc elf = tgc bal x urea dilution index (plasma urea concentration/bal urea concentration) [ ] . in all patients, distribution volume (vd), drug clearance (cl), and elimination half-life (t / ) were calculated after a single -mg intravenous dose at steady state. according to previous literature, based on early animal efficacy studies using a classification and regression tree approach, area under the concentration curve (auc) - /mic ratio ≥ . , . and . were used as pd targets for vap, intra-abdominal infections (iai) and skinsoft-tissue infections (ssti), respectively [ ] . graphing of data was undertaken using prism version . for windows (graphpad software, san diego, ca). isolates were identified by matrix-assisted laser desorption ionization-time-of-flight (maldi-tof) mass spectrometry (maldi biotyper, bruker daltonics gmbh, leipzig, germany). the in vitro susceptibility of the isolates was assessed with the vitek system (biomérieux, marcy l'etoile, france) or with panels manufactured by merlin diagnostica gmbh (bornheim, germany). results were interpreted in accordance with the european committee on antimicrobial susceptibility testing (eucast) clinical breakpoints. the presence of carbapenemase genes of blakpc, blandm, blavim, blaoxa- , blaoxa- , and blaoxa- types was determined by polymerase chain reaction and dna sequencing analysis using previously described protocols (endemiani, poirel, woodford) [ ] . all statistical analyses were performed using medcalc software, version . . (medcalc ® , mariakerke, belgium). kolmogorov-smirnov test was used to value the variables distribution. the data with a non-normal distribution were assessed with mann-whitney test and the median and selected centiles' ( th- th) value were given (interquartile range, iqr). the data with a normal distribution were assessed with student's test. categorical variables are presented as proportions and were analysed with the use of the chi square test or fisher's exact test, as appropriate. a p value < . was considered significant. due to the pk/pd design of the study, a sample size was not calculated, foreseeing the recruitment of at least patients during the predefined study period (july -july ). the clinical details of the non-obese patients included in the study are listed in table . albumin levels were quite low with an overall positive fluid balance at enrolment. median saps ii score was . and the most relevant comorbidities were cardiovascular diseases, chronic obstructive pulmonary disease, chronic renal failure and neoplasm (table ) . median sofa score was and many patients were in septic shock or presented with acute respiratory failure (arf) and acute kidney injury (aki) requiring mechanical ventilation (mv) and crrt, respectively. more than half of the patients had vap, followed by intra-abdominal infections and skin and soft-tissue infections: in the microbiological casemix gram-negative bacteria were mostly represented ( . %). median duration of tgc therapy was days and it was started empirically in half of the cases. the use of vasopressors and mv during tgc therapy was high and -day mortality rate was . %. eleven patients had a treatment failure, whilst the other successfully eradicated the infection. there were no between-group differences in terms of demographic aspects and main comorbidities. further the two groups were similar in terms of presenting features and outcomes with the exception of vap rate which was higher in the treatment success group ( . % vs. . %, p = . ) and a trend to a higher percentage of skin and soft-tissue infections and source control amongst patients who failed tgc treatment (p = . and p = . , respectively). a one-compartment model with first-order disposition processes adequately described the concentration-time curve, although significant interindividual variability was observed. vd, cl and t / were . l, . l/h and . h, respectively. median and iqr values of c max and c min were . [ . - . ] mcg/ml and . [ . - . ] mcg/ml (table ). figure shows the mean ± sd time-concentration profile at different time points of plasma tigecycline concentrations, compared with most frequently observed mic values ( . - . - . mcg/ml). auc - and iqr were calculated for each patient and the percentage of target attainment was also computed for nosocomial pneumonia (np) (auc - /mic breakpoint of . ), complicated intraabdominal infections (ciai) (auc - /mic breakpoint (fig. ) . conversely, no significant differences were found comparing mean ± se elf/plasma ratio at h and h ( ± . vs. . ± . ; p = . ) (fig. ) . our study shows an hd tgc ( mg ld, then mg q ) time-curve concentration with mean peak and trough levels of . mcg/ml and . mcg/ml, respectively (fig. ) . auc - /mic targets for nosocomial pneumonia (≥ . ) and complicated intra-abdominal infections (≥ . ) were obtained in the majority of cases in presence of bacteria with mic values ≤ . . otherwise, lower mic values (≤ . mcg/ml) were required to have satisfactory auc - /mic results ( %), whilst treating a skin/soft-tissue infection (fig. , table ). similar to plasma h and h, pulmonary concentrations ( . mcg/ml and . mcg/ml, respectively) were observed with a good median elf/plasma ratio of . % (table , fig. ). this high-dose regimen was associated with a . % of treatment success rate in a normal weight population including % of vap, % of ciai and % of ssti. tgc was used in half of the cases as targeted regimen for a median duration of days. the rates of septic shock, acute respiratory failure requiring mv and acute kidney injury requiring crrt were also high, with a mortality rate of . % (table ) . the pharmacokinetics/pharmacodynamics and tissue penetration of tigecycline have been extensively studied in various in vitro and human models [ ] . however, these studies were generally carried out in healthy volunteers, and few pharmacokinetic data concerning infected patients are available, which may present pathophysiologic conditions influencing the pharmacokinetic profile of this molecule. in addition, the majority of available data in infected patients derive from studies where normal doses are used, although for severe nosocomial infections a double-dose regimen is warranted [ , ] . recently, standard-dose tgc pharmacokinetics in ten critically ill patients has been studied [ ] . the authors observed that a larger body mass index was associated with increased tgc cl, but standard doses produced satisfactory plasmatic levels for vap and ciai treatment due to enterobacter cloacae, esherichia coli, klebsiella pneumoniae and methicillin-resistant staphylococcus aureus. however, higher dosages were required for the treatment of ssti, especially in obese patients. eleven out of patients in our cohort were receiving crrt whilst being treated with high-dose tgc. interestingly, in a recent paper, broeker and cow [ ] described the pk/pd of standard-dose tgc in eleven patients on continuous veno-venous haemodialysis (cvvhd) or haemodiafiltration (cvvhdf). tgc dialysability, as expressed by saturation coefficients ( . and . for cvvhd and cvvhdf, respectively), was very high, but the contribution of crrt tgc clearance was minimal (about l/h), compared with the total body clearance ( . l/h). peak drug concentrations were below mcg/ml and trough levels about . mcg/ml. the authors, considering the auc - /mic referral value for ciai ( . ), observed that such target was accomplished in % of the case if mic was ≤ . . this result is quite different from our findings where lower mic values are required to get the optimal pk/pd target. indeed, our results are in line with current available data, underlying the plus-value of increased dosages whilst treating critically ill patients especially with severe ciai and ssti. in addition, there is a high need of pk/pd data on tgc administered at higher than approved dosages, in light of the wide spread of increased resistance to tgc amongst gram-negative rods and acinetobacter spp. the first investigation on pk/pd of hd tgc derives from ramirez et al. who conducted a randomized phase trial to evaluate the clinical efficacy of two high-dosage regimen of tgc ( mg bid and mg bid) versus imipenem-cilastatin ( g every h) for the treatment of nosocomial pneumonia [ ] . in the clinically evaluable population, clinical cure with tgc mg bid was numerically higher than with bid and imipenemcilastatin ( g every h) ( % vs. . % vs. %). mean peak tgc concentration was about mcg/ml, declining to less than . mcg/ml after h, observing a safety profile comparable to that one known for the approved those. the only other study investigating the pk/pd of hd tgc profile was conducted by borsuk-de moor et al. in icu patients with severe infections [ ] . the time-concentration curve was similar to our data, displaying a peak concentration about mcg/ml and h level below . mcg/ml. interestingly, the authors developed a model which showed that no individual covariates may influence target concentrations, advising to modify tgc daily dosage according to pathogens type, susceptibility pattern and pk targets. tissue concentrations of antibiotics at the target site contribute to therapeutic effects: using plasma concentrations may frequently overestimate the target site concentrations and therefore clinical efficacy. this is the first study to report steady-state elf percentage penetration of tgc administered mg q after mg ld. considering the auc - /mic target of . , our data show satisfactory pulmonary concentrations with potential clinical success in %- % to %- % of the cases treating bacteria with mic of . - . mcg/ml to . - mcg/ml, respectively (fig. ) . these data confirm the results observed in healthy subjects by conte et al., where the c max /mic , auc/mic ratios, t > mic and extended serum and intrapulmonary half-lives following the standard regimen are favourable for the treatment of tgc-susceptible pulmonary infections [ ] . penetration ratio may be even higher when in presence of infected lungs. crandon et al. demonstrated in infected and noninfected mice lungs that the baseline penetration ratio of . is incremented to . in case of acinetobacter pneumonia [ ] . conversely, the majority of lung penetration occurs in alveolar cells, than in elf, as suggested by welte et al. in three cases of mdr lung infections [ ] . finally in a recent study on healthy subjects treated with standard tgc dose, the ratio of elf and auc to total plasma concentration of tigecycline was . and . , respectively [ ] . our study has several limitations. first, we adopted a single high-dose of tigecycline and we do not know if even higher dosages may result in better pk/pd profiles. second, we measured only pulmonary tissue concentration trough elf collection and we can only postulate the real tissue/plasma ratio for ciai and ssti which, additionally, accounted only for less than % of the cases. third, our analysis focused on total tgc concentration rather unbound auc - , due to the lack of clinical reliable breakpoint of fauc - /mic . fourth, we did not provide real mic values and we only simulated a wide range ( . - mcg/ml) to compute auc/mic ratios and pta percentages. fifth, we did not sampled bal from most hypoxemic/most severely patients, introducing a bias in the final results. finally, the sample size may be likely responsible of an underestimated interindividual variability in the observed pk/pd profile. our study is the first investigation where not only plasmatic but also pulmonary tigecycline concentrations are investigated during the treatment of severe infections in critically ill patients with high-dose tgc. observed plasmatic concentrations suggest the efficacy of this molecule for the treatment of susceptible pathogens, including pneumonia. higher than mg/day dosages and combination with other active molecules may be suggested whilst treating enterobacteriaceae and acinetobacter spp. with mic values close to the clinical breakpoint, especially in case of ssti and iai. supplementary information accompanies this paper at https ://doi. org/ . /s - 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achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with gram-negative pneumonia risk factors for mortality and cost implications of complicated intra-abdominal infections in critically ill patients pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia detection and characterization of antimicrobial resistance genes in pathogenic bacteria* pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines high-dose tigecycline for the treatment of nosocomial carbapenem-resistant klebsiella pneumoniae bloodstream infections: a retrospective cohort study once daily high dose tigecycline-pharmacokinetic/pharmacodynamic based dosing for optimal clinical effectiveness: dosing matters, revisited tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study population pharmacokinetics of high-dose tigecycline in patients with sepsis or septic shock steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline comparison of tigecycline penetration into the epithelial lining fluid of infected and uninfected murine lungs tigecycline possibly underdosed for the treatment of pneumonia: a pharmacokinetic viewpoint comparison of omadacycline and tigecycline pharmacokinetics in the plasma, epithelial lining fluid, and alveolar cells of healthy adult subjects springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. authors' contributions gdp and ma had full access to all the data in the study and take responsibility for the integrity and the accuracy of the data analysis. gdp, ms, pn and ma conceived the study, and participated in its design and coordination and helped to draft the manuscript. gdp was in charge of the statistical analysis, participated in analysis and interpretation of data, helped to draft the manuscript, and critically revised the manuscript for important intellectual content. ll, gmpc, msv, slc, lc, cg, gb, lm, sc and vdg collected the data for the study, recruited patients and did sample analyses. gdp, ll, gmpc, mt, ms, pn and ma participated in the conception, design and development of the database, helped in analysis and interpretation of data, helped in drafting of the manuscript and critically revised the manuscript for important intellectual content. all authors read and approved the final manuscript. fondi d' ateneo pn, università cattolica del sacro cuore (it). the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. the protocol was approved by the catholic university's ethical committee (approval number prot.sf / ). written informed consent was obtained from the patients' legally authorized representative. written informed consent was obtained from the patients' legally authorized representative. no individual person's data in any form are presented in this manuscript. the authors declare that they have no competing interests. key: cord- -zimkzbr authors: beloncle, françois m.; pavlovsky, bertrand; desprez, christophe; fage, nicolas; olivier, pierre-yves; asfar, pierre; richard, jean-christophe; mercat, alain title: recruitability and effect of peep in sars-cov- -associated acute respiratory distress syndrome date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: zimkzbr background: a large proportion of patients with a sars-cov- -associated respiratory failure develop an acute respiratory distress syndrome (ards). it has been recently suggested that sars-cov- -associated ards may differ from usual non-sars-cov- -associated ards by higher respiratory system compliance (c(rs)), lower potential for recruitment with positive end-expiratory pressure (peep) contrasting with severe shunt fraction. the purpose of the study was to systematically assess respiratory mechanics and recruitability in sars-cov- -associated ards. methods: gas exchanges, c(rs) and hemodynamics were assessed at levels of peep ( cmh( )o and cmh( )o) within h (day ) and from to days (day ) after intubation. the recruited volume was computed as the difference between the volume expired from peep to cmh( )o and the volume predicted by compliance at peep cmh( )o (or above airway opening pressure). the recruitment-to-inflation (r/i) ratio (i.e. the ratio between the recruited lung compliance and c(rs) at peep cmh( )o) was used to assess lung recruitability. a r/i ratio value higher than or equal to . was used to define highly recruitable patients. results: the r/i ratio was calculated in of the enrolled patients at day and in patients at day . at day , ( %) were considered as highly recruitable (r/i ratio median [interquartile range] . [ . – . ]) and ( %) were considered as poorly recruitable (r/i ratio . [ . – . ]). the pao( )/fio( ) ratio at peep cmh( )o was higher compared to peep cmh( )o only in highly recruitable patients ( [ – ] vs [ – ] mmhg; p < . ). neither pao( )/fio( ) or c(rs) measured at peep cmh( )o or at peep cmh( )o nor changes in pao( )/fio( ) or c(rs) in response to peep changes allowed to identify highly or poorly recruitable patients. conclusion: in this series of patients with sars-cov- associated ards, % were considered as highly recruitable and only % as poorly recruitable based on the r/i ratio performed on the day of intubation. this observation suggests that a systematic r/i ratio assessment may help to guide initial peep titration to limit harmful effect of unnecessary high peep in the context of covid- crisis. a very large proportion of patients admitted to icu for coronavirus disease (covid- ) fulfill acute respiratory distress syndrome (ards) criteria according to berlin definition [ ] [ ] [ ] . in a large series of severe acute respiratory syndrome coronavirus (sars-cov- )-associated respiratory failure, the majority of intubated open access *correspondence: francois.beloncle@univ-angers.fr département de médecine intensive-réanimation, chu d' angers, université d' angers, rue larrey, angers cedex , france full list of author information is available at the end of the article patients were ventilated with high level of positive endexpiratory pressure (peep) [ ] . however, information about specific individual characteristics of respiratory mechanics of sars-cov- -associated ards remains very limited [ ] [ ] [ ] . based on their experience during the crisis, some authors suggested that part of the sars-cov- associated ards may present relatively high respiratory system compliance (c rs ) and poor recruitability with peep, contrasting with severe hypoxemia. accordingly, high levels of peep might be harmful in this socalled "phenotype". the aim of this prospective study is to describe the characteristics of the respiratory mechanics of sars-cov- -associated ards, and, in particular, whether the lungs are recruitable with high levels of peep. patients admitted from march th to april nd to the medical icu of the university hospital of angers and intubated for sars-cov- -associated ards were prospectively included within h of intubation. ards was defined according to the berlin definition criteria [ ] . sars-cov- infection was confirmed by real-time reverse transcriptase-polymerase chain reaction (rt-pcr) assay of nasal swabs or lower respiratory tract samples (bronchoalveolar lavage or endotracheal aspirate). exclusion criteria were age lower than years, pneumothorax and use of extracorporeal membrane oxygenation (ecmo). our care strategy did not include high-flow nasal canula (hfnc), continuous positive airway pressure (cpap) or non-invasive ventilation for the management of patients with covid- . after intubation, patients received initially deep sedation and neuromuscular blockers for to h and were ventilated in volume-controlled mode with a tidal volume of ml/kg of predicted body weight (pbw) and a respiratory rate up to /min, adjusted to maintain arterial ph above . . peep was set according to gas exchange, hemodynamic tolerance and a plateau pressure lower or equal to cmh o. the fraction of inspired oxygen (fio ) was set for an arterial oxygen saturation (sao ) between and %. lung recruitment induced by high peep and detection of airway closure were assessed as previously described [ , ] . all the measurements were performed in supine semirecumbent position, with the head of the bed elevated at °, in volume-controlled mode with tidal volume of ml/kg pbw and a constant inspiratory flow of l/ min. after min at a peep level of cmh o, the respiratory rate was decreased to /min to eliminate possible intrinsic peep, and the expired tidal volume displayed by the ventilator was noted. peep was abruptly decreased to cmh o and expired volume displayed by the ventilator immediately after the maneuver was noted. the previous respiratory rate was resumed and peep was maintained at cmh o for the next min. plateau pressure, total peep, arterial blood gases and central venous blood gases (collected from a jugular venous line) were assessed at the two levels of peep (additional file : figure s ). mean arterial pressure (map) and heart rate were also recorded at the end of the application of each peep level. a low-flow ( l/min) inflation from peep cmh o (tidal volume = ml/kg pbw) was then performed to identify a possible airway closure [ ] . airway closure was identified by the inspection of the pressure-time curve and the airway opening pressure (aop) was measured using cursors on the ventilator screen. this maneuver was performed in the supine position within h after intubation (day ) and from day to day after intubation (day ) in patients still ventilated in volume-controlled mode, neither triggering the ventilator nor on ecmo. the recruited lung volume was computed as the volume expired from peep to cmh o (displayed on the ventilator screen immediately after an abrupt decrease in peep) subtracting from the previous expired tidal volume and from the lung volume predicted by the compliance at low peep (additional file : figure s ) [ , ] . the lung volume predicted by the compliance at low peep represents the minimum predicted change in lung volume corresponding to the change in pressure between the peep levels (i.e. the change in lung volume if no recruitment occurs) and is equal to the product of c rs at peep cmh o (or above aop) and peep change (i.e. cmh o or -aop). the r/i ratio represents the ratio between the compliance of the recruited lung and the compliance of the "baby lung". briefly, the compliance of the recruited lung was calculated as the recruited lung volume divided by the difference between the peep levels (i.e. cmh o) in patients without airway closure at cmh o or by the difference between cmh o and aop, in patients with airway closure above cmh o [ ] . the respiratory system compliance at peep cmh o or above aop was used as a surrogate for the compliance of the baby lung. a high r/i ratio is considered to be associated with a high potential for lung recruitment. as previously described, a threshold of . was used to differentiate poorly recruitable from highly recruitable patients [ ] . the following data were collected at inclusion (i.e. on the day of intubation): age, past medical history, sequential organ failure assessment (sofa) score [ ] and simplified acute physiologic score ii (saps ii) [ ] , partial pressure of arterial oxygen (pao ), fraction of inspired oxygen (fio ), partial pressure of arterial carbon dioxide (paco ), tidal volume, respiratory rate, minute ventilation, set peep and plateau pressure. the delay from symptom onset to icu admission and from icu admission to intubation was also reported. the estimated shunt fraction was calculated, based on the venous admixture determination [ ] , considering central venous oxygen saturation (scvo ) as an acceptable surrogate for mixed venous oxygen saturation [ ] : with cao , cvo and cco being the arterial, central venous, and ideal capillary o concentration values, respectively. the c rs was computed as tidal volume divided by the difference between plateau pressure and total peep (or aop in patients with airway closure at cmh o). for each patient, the extension and severity of lung opacities were assessed on the first chest x-ray performed after the intubation by independent observers who were unaware of the patient's clinical data, using the rale score [ ] . in this score, each quadrant is scored for extent of consolidation (from to ) and density of opacification (from to ). the rale score corresponds to the sum of the products of the consolidation and density scores of each of the quadrants (maximum score = ). data are presented as median [interquartile range] or number (percentage). the study population was divided into groups according to the r/i ratio at day . highly recruitable patients group was composed of patients with r/i ratio higher than or equal to . at day and the patients with r/i ratio lower than . made up the poorly recruitable patients group. the two groups of patients were compared using mann-whitney u-test or fisher's exact test as appropriate. paired data were compared using wilcoxon test for paired data. all tests were estimated shunt fraction: performed with a type i error set at . . the statistical analysis was performed using prism (graphpad software v . b, la jolla, ca, usa). twenty-six patients were included in this study. the peep trial maneuver for recruitability assessment was rapidly interrupted in one patient at day because of major desaturation on peep cmh o. twenty-five patients were thus analyzed. main characteristics of the patients and respiratory parameters on the day of intubation are presented in tables and . the r/i ratio was assessed in patients at day and in patients at day . among the patients evaluated at day , ( %) were considered as highly recruitable (r/i ratio . [ . - . ]) and ( %) were considered as poorly recruitable (r/i ratio . [ . - . ]); table and fig. table and additional file : figure s . among the patients considered as highly recruitable at day , a second r/i ratio assessment was performed at day in patients. among these patients, remained highly recruitable and became poorly recruitable, fig. . in addition, patient was switched early to pressure support, patients were discharged from icu, and died before the second r/i ratio assessment. among the patients considered as poorly recruitable at day , a second r/i ratio assessment was performed at day in patients. among these patients, became highly recruitable and remained poorly recruitable, fig. . the other patients were switched early to pressure support. the pao /fio ratios measured at peep cmh o and at peep cmh o were not different in the groups; fig. table and fig. . in addition, c rs was not non-invasive support before intubation, n (%) ( ) ( ) ( ) fig. and additional file : figure s . we did not observe significant changes in map and hr between peep cmh o and peep cmh o in the groups; additional file : figure s . the rale score of the chest x-ray performed after intubation did not differ between the groups ( . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the highly recruitable patients group vs [ . - ] , in the poorly recruitable patients group, p = . ); additional file : figure s . the main results of the present case series could be summarized as follows: ( ) the majority of these sars-cov- -associated ards exhibit relatively preserved static c rs and are considered as potentially recruitable based on r/i ratio soon after intubation; ( ) neither individual p-values refer to the comparison between the highly and poorly recruitable patients groups. r/i ratio is by definition higher in the highly recruitable than in the poorly recruitable patients values of pao /fio ratio and static c rs measured either at high or low peep nor changes of these parameters with change of peep allow to identify highly recruitable or poorly recruitable patients; ( ) among patients initially considered as poorly recruitable, some of them become highly recruitable days later. in the present series of sars-cov- -associated ards, the initial respiratory mechanics assessment performed soon after intubation at peep cmh o and cmh o allowed to identify patients as potentially highly recruitable and as poorly recruitable based on the previously reported r/i ratio [ ] . interestingly, the second complete respiratory mechanics assessment performed to days later in patients suggested that initial status may change more frequently from poorly recruitable to highly recruitable than the reverse. the present small cases series is the first to describe early and complete respiratory mechanics evaluation in sars-cov- -associated ards consistent with the " phenotypes" model proposed by gattinoni et al. [ ] . our observations extend those initially reported in three small cases series showing essentially low or variable potentials of recruitment with peep [ ] [ ] [ ] . in the recently reported chinese series of sars-cov- -associated ards, all patients were initially considered as poorly recruitable based on the same method to measure r/i ratio [ ] . interestingly, repetitive measurements showed that some of them became recruitable potentially depending on the time course evolution of the disease and the respiratory treatment they received (notably prone positioning). authors concluded that r/i ratio is feasible, even in the constrained covid- environment and may allow to guide individual titration of peep to limit potential harmful effects expected with high peep in poorly recruitable patients. most ( %) of these patients received niv or hfnc before intubation for a median of [iqr, [ ] [ ] [ ] [ ] days. this could lead to patient self-inflicted lung injury [ ] that may explain, at least in part, their low respiratory system compliance (around ml/cmh o) after intubation. this may also have participated to the apparent beneficial effect of prone position on recruitment in this series despite initial poor recruitability. in the italian series of sars-cov- -associated ards, the near-normal compliance of the respiratory system ( ml/cmh o on average) contrasted with severe hypoxemia suggesting relatively preserved lung volumes which is unusual in non-covid- ards [ , ] . based on these original observations, authors challenged the classical recommendations for peep titration and prone positioning based on the severity of hypoxemia [ ] , suggesting that peep may lead to severe hemodynamic impairment and fluid retention in poorly recruitable patients while prone position may be less efficient imposing an unnecessary additional workload in the context of the pandemic. the same group of authors proposed a concise physiological description of what they called "phenotypes l and h". briefly they opposed the possible high proportion of poorly recruitable patients with near-normal compliance ("l") to patients with low compliance and high potential for recruitment ("h" not different from classical non-covid- ards) that may benefit from higher peep and prone position. authors mentioned that the phenotype may change with time. the mix of poorly recruitable and higly recruitable patients that we observed in the present study based on r/i ratio, roughly fit with this "h" and "l" description. in fact, pao /fio ratio was significantly increased at peep cmh o compared to cmh o only in highly recruitable patients. conversely, poorly recruitable patients exhibited a non-significant trend toward higher c rs at low peep compared to highly recruitable patients. moreover, the trend in decrease in c rs observed in these patients when peep is increased may reflect overinflation thus indicating the risk associated with high peep in these patients. of note, the increase in pao /fio ratio with peep in poorly recruitable patients may be explained, at least in part, by a potential reduction in cardiac output induced by peep that may have contributed to decrease the shunt fraction [ ] . rather than the schematic opposition of two phenotypes, our results suggest that recruitment with peep in these patients must be individually evaluated since it may vary largely depending on the initial clinical presentation as well as the time course evolution under treatment. our study presents important limitations. first of all, the small number of patients enrolled in this series does not allow to conclude about the expected repartition of the two proposed phenotypes in a large population of sars-cov- -associated ards. moreover, initial respiratory management (i.e. prolonged use of hfnc, cpap or non-invasive ventilation vs early intubation) is a confoundable parameter that may impact the respiratory pattern recorded immediately after intubation. second, the respiratory mechanics characterization at two levels of peep and the r/i ratio do definitively not allow to determine accurately the optimal peep level. finally, the second respiratory mechanics evaluation was not available in all patients thus limiting the possibility to assess the impact of prone positioning and peep settings that may change the evolution of the phenotype along the time course evolution of the disease. in this series of sars-cov -associated ards, early respiratory mechanics assessment (at and cmh o of peep) and r/i ratio calculation showed a mix of highly recruitable and poorly recruitable patients. neither individual values of pao /fio ratio or c rs on low or high peep nor their changes after a change of peep allowed to distinguish highly recruitable from poorly recruitable patients. present observations suggest that a systematic r/i ratio evaluation may be useful to guide initial setting of peep in the context of sars-cov -associated ards. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file : figure s . a. study protocol. positive end-expiratory pressure level (peep) was set to cmh o. arterial and central venous blood gases were collected after a min period and respiratory mechanics was assessed. respiratory rate (rr) was decreased to /min and peep was decreased to cmh o (see below, additional file : figure s b ). after a min period with peep cmh o, arterial and central venous blood gases were collected and respiratory mechanics was assessed. a low flow insufflation ( l/min) from peep cmh o was performed after a prolonged expiration. a visual analysis of the pressure-time curve on the ventilator screen allowed to identify a potential airway closure (and to measure a potential airway opening pressure) (see a representative tracing below). b. measurement of the recruited lung volume. after decreasing rr to / min, expired tidal volume displayed by the ventilator at peep cmh o baseline characteristics and outcomes of patients infected with sars-cov- admitted to icus of the lombardy region risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease pneumonia in wuhan, china acute respiratory distress syndrome: the berlin definition lung recruitability in sars-cov- associated acute respiratory distress syndrome: a singlecenter, observational study covid- does not lead to a "typical" acute respiratory distress syndrome potential for lung recruitment and ventilation-perfusion mismatch in patients with the acute respiratory distress syndrome from coronavirus disease potential for lung recruitment estimated by the recruitment-toinflation ratio in acute respiratory distress syndrome. a clinical trial airway closure in acute respiratory distress syndrome: an underestimated and misinterpreted phenomenon peep-induced changes in lung volume in acute respiratory distress syndrome. two methods to estimate alveolar recruitment implementing a bedside assessment of respiratory mechanics in patients with acute respiratory distress syndrome the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine a new simplified acute physiology score (saps ii) based on a european/north american multicenter study fifty years of research in ards. gas exchange in acute respiratory distress syndrome can central venous blood replace mixed venous blood samples? severity scoring of lung oedema on the chest radiograph is associated with clinical outcomes in ards covid- pneumonia: different respiratory treatments for different phenotypes? intensive care med mechanical ventilation to minimize progression of lung injury in acute respiratory failure lung recruitment in patients with the acute respiratory distress syndrome the berlin definition of ards: an expanded rationale, justification, and supplementary material publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations in the context of covid- crisis, authors would like to greatly acknowledge all the medical and non-medical teams of the angers medical icu working in constrained environment. was noted. peep was abruptly decreased to cmh o and expired volume displayed by the ventilator immediately after the maneuver was noted. plateau pressure at peep cmh o was measured. initial rr was then resumed. c. representative tracing of a low flow insufflation allowing to identify a complete airway closure and to measure the airway occlusion pressure (aop).additional file : figure s . distribution of recruited lung volume (v rec ) within h after intubation in the highly recruitable and poorly recruitable patients groups. *, p < . . horizontal lines represent median and interquartile range values. authors' contributions fb, jcr and am contributed to the study conception and design. fb, bp, cd, nf and pyo performed the data collection and the initial data analysis. fb, jcr and am prepared the first draft of the manuscript. all authors contributed to the data analysis and to the critical revision. all authors read and approved the final manuscript. bp received a -year research fellowship grant from the university hospital of réunion, france. cd and nf received a -year research fellowship grant from the university hospital of angers, france. the datasets analyzed during the current study are available from the corresponding author on reasonable request the study protocol was approved by the ethics committee of the university hospital of angers (# / ). the study reports data routinely acquired in usual care, signed informed consent was not required. not applicable. key: cord- -furt xcn authors: hraiech, sami; bonnardel, eline; guervilly, christophe; fabre, cyprien; loundou, anderson; forel, jean-marie; adda, mélanie; parzy, gabriel; cavaille, guilhem; coiffard, benjamin; roch, antoine; papazian, laurent title: herpes simplex virus and cytomegalovirus reactivation among severe ards patients under veno-venous ecmo date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: furt xcn background: herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ards). however, little is known about herpes simplex virus (hsv) and cytomegalovirus (cmv) reactivation occurring in patients with severe ards under veno-venous extracorporeal membrane oxygenation (ecmo). we tried to determine the frequency of herpesviridae reactivation and its impact on patients’ prognosis during ecmo for severe ards. results: during a -year period, non-immunocompromised patients with a severe ards requiring a veno-venous ecmo were included. sixty-seven patients ( %) experienced hsv and/or cmv reactivation during ecmo course ( viral co-infection, hsv alone, and cmv alone). hsv reactivation occurred earlier than cmv after the beginning of mv [( – ) vs. ( – ) days; p < . ] and after ecmo implementation [( – ) vs. ( – ) days; p < . ]. in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation [( – . ) vs. . ( – ) days; p < . ], a longer duration of ecmo [ ( – . ) vs. ( – ) days; p < . ], and a prolonged icu [ ( . – . ) vs. ( – ) days; p < . ] and hospital stay [ ( – . ) vs. ( – ) days; p < . ] as compared to non-reactivated patients. however, in multivariate analysis, viral reactivation remained associated with prolonged mv only. when considered separately, both hsv and cmv reactivation were associated with a longer duration of mv as compared to non-reactivation patients [ ( . – ) and ( . – ), respectively, vs. . ( – ) days; p < . ]. co-reactivation patients had a longer duration of mv [ . ( – . ); p < . ] and icu stay [ . ( . – ) vs. . ( . – . ) and ( – . ), respectively] as compared to patients with hsv or cmv reactivation alone. in multivariate analysis, hsv reactivation remained independently associated with a longer duration of mv and hospital length of stay. conclusions: herpesviridae reactivation is frequent among patients with severe ards under veno-venous ecmo and is associated with a longer duration of mechanical ventilation. the direct causative link between hsv and cmv reactivation and respiratory function worsening under ecmo remains to be confirmed. herpes simplex virus (hsv) and cytomegalovirus (cmv) belong to the herpesviridae family and are characterized by an often asymptomatic primo-infection generally during childhood followed by a latency phase. in immunocompromised subjects, herpesviridae are common viral causes of opportunistic infections. but hsv and cmv reactivations are also frequently reported in intensive care unit (icu) non-immunocompromised patients [ , ] . reactivation ranges from to % and to % for hsv and cmv, respectively [ , ] . herpesviridae reactivation in immunocompetent icu patients is associated with poorer outcome [ ] . hsv pulmonary reactivation has been described to be associated with a longer mechanical ventilation (mv) duration, icu stay and mortality [ , , ] . cmv reactivation is also associated with a higher mortality, mv duration and icu length of stay [ ] . in particular, cmv has been identified as a cause of persistent acute respiratory distress syndrome (ards) [ ] and has also been shown to increase the mortality in ards patients [ ] . however, despite these associations, the debate on the proper pathogen role of herpesviridae rather than being a witness of patients' severity is still ongoing. studies failed to demonstrate that cmv prophylaxis was able to decrease il- plasma levels in cmv seropositive critically ill patients [ ] or to decrease mortality [ ] . the role of herpesviridae pre-emptive treatment among icu patients has been recently evaluated in a randomized controlled trial (rct) (nct ). the data concerning hsv showed that preemptive acyclovir did not decrease the duration of mv although a trend towards lower mortality was found in treated patients [ ] . the most frequent risk factors for cmv and hsv reactivation in the icu are patients severity, sepsis, prolonged mv [ ] , high-dose corticosteroid therapy, acute renal failure or massive transfusion [ ] , with a strong association for mv and sepsis [ ] . patients under veno-venous extracorporeal membrane oxygenation (vv ecmo) for severe ards [ ] often combine several or all of these risk factors [ ] . despite the uncertainties regarding the exact role of herpesviridae reactivation in immunocompetent critically ill patients, it might add to the pulmonary pathology in patients with ards. in experimental studies, cmv reactivation led to increased pulmonary fibrosis [ ] and accessing bacterial pneumonia [ ] . these findings suggest that herpesviridae-related pulmonary pathology may be causally linked to the clinical disease course following ards onset, especially in the most severely ill patients who require prolonged mechanical ventilation, and might particularly concern patients under ecmo. however, despite the tight link that seems to exist between herpesviridae, mechanical ventilation and ards, no study has investigated the occurrence of hsv and/or cmv reactivation in patients under vv ecmo. in this study, we aimed to assess the frequency of herpesviruses reactivation during ecmo course and to determine its impact on patients' prognosis. we conducted an observational, retrospective study in a medical icu (ards and ecmo referee center) at the marseille university hospital between december and april . patients aged or more, hospitalized in the icu for severe ards requiring a vv ecmo for days or more were included. hsv and/or cmv reactivation (see definition below) occurring after ecmo insertion was screened for these patients. patients with immunosuppression (immunosuppressive treatments including corticosteroids > . mg/kg/day prednisoneequivalent within days prior to inclusion, severe neutropenia < . g/l of neutrophils, hiv seropositivity, bone marrow or solid organ transplantation), antiviral therapy against hsv and/or cmv prior to inclusion, or hsv/cmv reactivation known at the time of ecmo insertion were excluded. at the time of the study, hsv and cmv screening were routinely performed twice weekly in all patients under mv. hsv reactivation was defined by a positive qualitative throat sample (virocult ® ) pcr. cmv reactivation was defined by a positive quantitative blood pcr with a copy number > /ml. when a broncho-alveolar lavage (bal) was performed for suspicion of ventilator-associated pneumonia, hsv and cmv pcr were systematically realized in bal and blood. cmv viral loads were converted in iu/ml and qualified as "high reactivation" for viral loads greater than or equal to iu/ml or "low reactivation" for viral loads of - iu/ml [ ] . cmv antigenemia was also researched in case of reactivation suspicion. the following data were retrospectively recorded from the patients' medical file: age, sex, simplified acute physiologic score ii (saps ii) [ ] , sequential organ failure assessment (sofa) score [ ] , presence of co-morbidities, presence of previous immunosuppression, cause of ards, date of mv initiation, date of ecmo implementation, other organ failure associated with ards during icu stay (in particular need for catecholamines or renal replacement therapy), blood transfusion, post-aggressive pulmonary fibrosis (defined by an alveolar procollagen iii higher than µg/l) [ ] , time of hsv/cmv reactivation, delay between mv and hsv/cmv reactivation, delay between ecmo and hsv/cmv reactivation, duration of mv (from the day of intubation to the day of mv weaning), ecmo duration (from the day of ecmo implementation to its removal or death), ecmo-free days at day , ventilator-free days (vfd) at day , icu length of stay [from the day of icu admission (in the first icu if the patient was referred from another hospital) to discharge], hospital length of stay [from the admission to hospital (in the original hospital if the patient was referred from another hospital) to discharge to home or to rehabilitation ward], icu and hospital mortality, acyclovir or ganciclovir treatment after reactivation under ecmo. statistical analysis was performed using ibm spss statistics version . (ibm spss inc., chicago, il, usa). first, a univariate analysis was performed. data were expressed as mean ± the standard deviation or median with interquartile range for the quantitative variables, and as numbers and percentages for the categorical variables. patient characteristics and clinical outcomes were compared to the viral reactivation status of the patients or antiviral treatment. groups were compared using the chi-square or fisher's exact test for categorical characteristics, and using the student's t test or mann-whitney u test for continuous ones, as appropriate. then a multivariate analysis was performed to assess the independent effect of viral reactivation on different outcomes. multiple linear regression was used to construct models. variables that were marginally significant (p < . ) in the univariate analysis, and that had clinical relevance were included in the regression models. beta coefficients and their p values were presented. a two-sided p value less than . was considered statistically significant. during the study period, patients were admitted to our icu for severe ards requiring a vv ecmo for days or more (see flowchart, fig. ). of these, patients were excluded because of immunosuppression ( patients), hsv/cmv reactivation at the time of ecmo implementation ( patients) or acyclovir/ganciclovir treatment before ecmo ( patients). among the patients included, patients ( %) experienced hsv and/or cmv reactivation during the icu stay and ( %) were free from hsv/cmv reactivation at the time of icu discharge or death. population's characteristics are presented in table . patients with hsv/cmv reactivation had a longer mv before ecmo than non-reactivated patients (p < . ). mean cmv viral loads (in blood or bal) were ± iu/ml with a high reactivation for ( %) patients. clinical outcomes are presented in table . patients exhibiting hsv/cmv reactivation received more transfusion [ ( - . ) vs. ( - ) red cells pellets; p = . ]. pulmonary fibrosis, diagnosed by an alveolar procollagen iii > µg/l, was not different between both groups. in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation [ ( - when separating patients according to hsv, cmv, and co-reactivation (hsv and cmv), we found that hsv reactivation was associated with a longer duration of in multivariate analysis (table ) , only hsv reactivation remained independently associated with a longer duration of mv and hospital length of stay but a shorter icu stay. thirty-four patients ( %) received an antiviral treatment (acyclovir or ganciclovir) during ecmo course. no difference in clinical outcomes was found between treated and untreated patients except a trend towards longer duration of mv for treated patients (additional file : table s ). multivariate analysis evaluating, after adjustment on patients' severity and length of mv and ecmo duration before reactivation, the clinical impact of hsv/ cmv reactivation. the coefficient designates the number of days by which the different endpoints are affected data are presented as median and interquartile range or absolute value and percentage a p < . compared with non-reactivation group until today, no data have been published concerning herpesviridae reactivation in icu patients under vv ecmo for severe ards. in this retrospective study covering a -year period, we found that hsv/ cmv reactivation was frequent and concerned more than half non-immunocompromised patients, which is higher than that described in previous studies including all icu patients [ , , ] . this might be explained by several reasons: the use of pcr to diagnose reactivation with a higher sensitivity than older technics, the age of our cohort of patients (with a high probability of seropositivity for hsv and cmv at icu admission) and the frequency of sepsis with a probable induced "immunoparalysis" [ ] . in our cohort, hsv reactivation occurred earlier than cmv reactivation and the median time of reactivation for both viruses was comparable to what is described in "non-ecmo" patients [ ] . cmv viral loads in blood and bal were high in almost all patients. elevated cmv viremia is associated with a higher risk of death or prolonged hospitalization [ ] . patients included were comparable except for the duration of mv before ecmo that was longer in the reactivation group. it is well known that mv is a risk factor for herpesviridae reactivation with a strong association for cmv [ ] . we found that herpesviridae reactivation was associated with a prolonged mv, this association persisting in multi-variate analysis. we also found in these patients a prolonged ecmo duration, icu, and hospital stay, although not confirmed in multivariate analysis. in a recently published meta-analysis, li et al. [ ] showed that cmv reactivation was associated with an increase of days in mv and a days increase in icu stay. these results confirmed those published by limaye et al. [ ] , which showed that cmv viremia among icu patients was associated with a higher risk of death or prolonged icu stay > days. similarly, in a case-control study [ ] , cmv reactivation was associated with a prolonged duration of mv and icu stay. in a specific population of ards patients, ong et al. [ ] demonstrated that patients with cmv reactivation had a ( - ) days median duration of mv as compared to ( - ) days for non-reactivated patients. icu length of stay was also longer [ ( - ) vs. ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) days] for reactivated patients. same results have been published concerning hsv reactivation [ , ] , especially during ards. our findings suggest that herpesviridae reactivation is associated with worse outcomes for ards patients including when they are under ecmo. when examining the impact of each virus separately, we found that both hsv and cmv were associated with a prolonged mv, and also ecmo duration for hsv. coreactivation had a negative effect not only on mv and ecmo duration but also on icu and hospital stay, as compared to patients free from reactivation or with only one virus. hsv was independently associated with a longer duration of mv and hospital length of stay but, surprisingly, a shorter icu stay. these results highlight the potential negative role of hsv in ards patients under ecmo. very recently, luyt et al. [ ] showed that preemptive treatment with acyclovir, compared to placebo, for mechanically ventilated patients with oropharyngeal hsv reactivation, was not associated with shorter mv duration. however, a trend towards lower day- mortality was observed in the acyclovir group. in our cohort, more than half of the patients were treated after the diagnosis of viral reactivation. treatment with acyclovir or ganciclovir did not improve the outcomes, with a trend for longer duration of mv in the sub-group of treated patients. these results might be explained by the fact that anti-viral treatment was decided by clinicians more frequently in case of worsening respiratory status, persisting fever or end-organ hsv/cmv disease, and so reserved for the most severe patients. we did not find any increase in renal failure in patients receiving antiviral drugs, which was also noticed in luyt et al. 's study [ ] . however, we cannot exclude any other side effects. our study has some limitations. first, the retrospective design of our cohort, counterbalanced by the important number of patients included during this -year period. second, the applicability of our results to the general population of patients under ecmo must be considered cautiously considering the high rate of patients treated with antiviral drugs after reactivation. however, in non-emco patients, routine screening of herpesviridae has been reported as well as the use of antiviral treatment despite the lack of recommendation [ , , ] . third, few patients developed an isolated cmv reactivation. this precludes to conclude clearly on the specific impact of cmv in our cohort of patients. fourth, our methods do not prevent competing risks. in particular, the difference in mv duration between reactivated and non-reactivated patients might have been influenced by the high mortality reported. however, this mortality was similar in both groups and the difference of mv duration persisted when considering only the patients discharged alive from the icu. finally, despite the statistical association, it is not possible to conclude whether herpesviridae reactivation is directly responsible for worse clinical outcomes or if it is a consequence and a witness of the severity of the disease, as in non-ecmo populations [ ] . herpesviridae reactivation is frequent among patients with severe ards under veno-venous ecmo and is associated with a prolonged mechanical ventilation. this association is present for hsv as well as cmv and also for co-reactivation. the direct causative link between hsv and cmv reactivation and respiratory function worsening under ecmo remains to be confirmed. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file : table s . clinical outcomes according to anti-viral treatment. abbreviations ards: acute respiratory distress syndrome; bal: broncho-alveolar lavage; cmv: cytomegalovirus; ecmo: extracorporeal membrane oxygenation; hiv: human immunodeficiency virus; hsv: herpes simplex virus; icu: intensive care unit; il- : interleukine ; iu/ml: international units/milliliter; mv: mechanical ventilation; pcr: polymerase chain reaction; saps ii: simplified acute physiologic score ii; sofa: sequential organ failure assessment; vfd: ventilator free days; vs.: versus; vv: veno-venous. active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation cytomegalovirus reactivation in icu patients cytomegalovirus reactivation in critically-ill immunocompetent patients cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients is acyclovir effective among critically ill patients with herpes simplex in the respiratory tract? cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis a contributive result of open-lung biopsy improves survival in acute respiratory distress syndrome patients cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome effect of ganciclovir on il- levels among cytomegalovirus-seropositive adults with critical illness: a randomized clinical trial safety and efficacy of antiviral therapy for prevention of cytomegalovirus reactivation in immunocompetent critically ill patients: a randomized clinical trial acyclovir for mechanically ventilated patients with herpes simplex virus oropharyngeal reactivation: a randomized clinical trial prevalence and mortality associated with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit cytomegalovirus infection in critically ill patients: associated factors and consequences cytomegalovirus infection in immunocompetent critically ill adults: literature review formal guidelines: management of acute respiratory distress syndrome long-term neurocognitive outcome is not worsened by of the use of venovenous ecmo in severe ards patients pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice cytomegalovirus reactivation enhances the virulence of staphylococcus aureus pneumonia in a mouse model a new simplified acute physiology score (saps ii) based on a european/north american multicenter study the sofa (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. on behalf of the working group on sepsis-related problems of the european society of intensive care medicine type iii procollagen is a reliable marker of ards-associated lung fibroproliferation early herpes and ttv dnaemia in septic shock patients: a pilot study cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we acknowledge mrs claudine marion and sabine depetris for their help.authors' contributions sh, eb, cg, ma, gp, gc and bc collected and analyzed the data. sh, eb, cg, ar and lp analyzed and interpreted more precisely the data. cf, al, sh and cg performed the statistical analysis. sh, eb and lp wrote the manuscript. all authors read and approved the final manuscript. the authors received no funding for this work. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. patients and their relatives were informed of the possibility of the use of medical data for retrospective studies and did not manifest opposition. the study was approved by the "portail d'accès aux données de santé de l' assistance publique des hopitaux de marseille" ("règlement général pour la protection des données" registration number - ). not applicable. the authors declare that they have no competing interests. key: cord- -tcnpskpy authors: wang, ke; zhao, wei; li, ji; shu, weiwei; duan, jun title: the experience of high-flow nasal cannula in hospitalized patients with novel coronavirus-infected pneumonia in two hospitals of chongqing, china date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: tcnpskpy background: the outbreak of a novel coronavirus ( -ncov)-infected pneumonia (ncip) is currently ongoing in china. most of the critically ill patients received high-flow nasal cannula (hfnc) oxygen therapy. however, the experience of hfnc in this population is lacking. methods: we retrospectively screened confirmed patients with ncip in two hospitals of chongqing, china, from january st to march th, . among them, ( . %) patients experienced severe acute respiratory failure including patients ( %) treated with hfnc as first-line therapy, patients ( %) treated with noninvasive ventilation (niv) and one patient ( %) treated with invasive ventilation. hfnc failure was defined by the need of niv or intubation as rescue therapy. results: of the hfnc patients, ( %) experienced hfnc failure. the hfnc failure rate was % ( / ) in patients with pao( )/fio( ) > mm hg vs. % ( / ) in those with pao( )/fio( ) ≤ mm hg (p = . ). compared with baseline data, the respiratory rate significantly decreased after – h of hfnc in successful group [median (iqr: – ) vs. ( – ), p = . ]. however, it did not in the unsuccessful group. after initiation of niv as rescue therapy among the patients with hfnc failure, pao( )/fio( ) significantly improved after – h of niv [median ( – ) mmhg vs. (iqr: – ) under hfnc, p = . ]. however, two out of seven ( %) patients with niv as rescue therapy ultimately received intubation. among the patients with severe acute respiratory failure, four patients were eventually intubated ( %). conclusions: our study indicated that hfnc was the most common ventilation support for patients with ncip. patients with lower pao( )/fio( ) were more likely to experience hfnc failure. in december , acute respiratory infection due to novel coronavirus ( -ncov), now known as novel coronavirus-infected pneumonia (ncip), emerged in wuhan, china [ , ] . the main symptoms were fever, cough, dyspnea, myalgia, fatigue, and radiographic evidence of pneumonia [ ] [ ] [ ] . human-to-human transmission of ncip has been reported, even in the incubation period [ ] [ ] [ ] . in a hospital, % of health care workers and % of patients who were already hospitalized for other reasons have been identified as presumed hospital-related transmission and infection [ ] . the ncip has spread worldwide and many countries have reported cases of ncip [ ] [ ] [ ] [ ] . as of february , , , cases with ncip were confirmed and cases died in china [ ] . the who has declared the outbreak of ncip as a public health emergency of international concern on january , . in the hospitalized ncip patients, the time from disease onset to shortness of breath was median days and to development of ards was median . days [ ] . and the rate of development of ards ranged from to % [ , ] . most of the patients received oxygen therapy. highflow nasal cannula (hfnc) is one of the oxygen therapies for critically ill patients [ ] . however, to the best of our knowledge, there were no studies to report the use of hfnc in hospitalized ncip patients. here, we aimed to report the experience of hfnc in this population. this was a retrospective observational study performed in two hospitals of chongqing, china. the -ncov was confirmed by real-time reverse transcription polymerase chain reaction (rt-pcr) assay [ ] . the diagnosis of ncip was based on clinical characteristics, chest imaging and rt-pcr assay. we screened all the patients with ncip in two hospitals (yongchuan hospital of chongqing medical university and chongqing public health medical center) from january st to march th, . the ncip patients who required hfnc, niv or invasive ventilation to improve oxygen were classified as severe acute respiratory failure. the study protocol was approved by the local ethics committee and institutional review board (approval number ). as this was a retrospective study, the informed consent was waived. the critically ill patients who received hfnc (fisher & paykel, auckland, new zealand, or humid-bm, respircae medical, shen yang, china) were managed by their attending physicians. the temperature was set at to °c, the flow was set at to l/min, and the fraction of inspired oxygen concentration (fio ) was set to maintain the spo more than %. the continuous use of hfnc was required for all the patients at the initial phase. when the respiratory failure was reversed, the intermittent use of hfnc was performed. we gradually increased the time of standard oxygen and shortened the duration of hfnc until the hfnc was totally weaned. however, if the respiratory failure progressively deteriorated, the attending physicians determined to use noninvasive ventilation or invasive mechanical ventilation as a rescue therapy. hfnc failure was defined by the need of niv or intubation as rescue therapy. before the use of hfnc, we collected the demographics, vital signs, laboratory tests and the arterial blood gas tests. the baseline pao /fio was measured under standard oxygen just before hfnc. the fio was estimated as follows: fio (%) = + * flow (l/min) [ ] . we also assessed the disease severity by acute physiology and chronic health evaluation ii (apache ii) score and organ failure by sequential organ failure assessment (sofa) score. at - h and termination of hfnc, we also collected the vital signs and arterial blood gas tests. among the patients who experienced hfnc failure and needed niv as rescue therapy, these variables were also collected at - h and termination of niv. continuous variables were reported as mean value (standard deviation) or median value [interquartile range (iqr)] when appropriate. the differences between two groups were analyzed by student's t test or mann-whitney u test. the differences between different time points within group were analyzed by the use of paired student's t test. categorical variables were reported as number and percentage, and analyzed using the chi-squared test or fisher's exact test. a p value < . was considered significant. we screened patients with ncip for eligibility ( fig. ) . twenty-seven out of ( . %) patients experienced severe acute respiratory failure. among the patients with severe acute respiratory failure, hfnc was used as first-line therapy in ( %) patients, noninvasive ventilation (niv) in ( %) patients, and invasive ventilation in one ( %) patient. four patients were eventually intubated ( %). the characteristics of the patients treated with hfnc as first-line therapy are summarized in table . among the patients treated with hfnc, ( %) experienced hfnc failure and needed niv as a rescue (fig. ) . however, the failure rate was % in patients with pao / fio ≤ mmhg. the comparisons between patients with hfnc success and failure are summarized in table table ). to the best of our knowledge, there were no studies to report the use of hfnc in patients with ncip. our study originally reported that hfnc was the most common ventilation strategies for ncip patients. patients with lower pao /fio were more likely to experience hfnc failure. forty-one percent of patients required niv as rescue therapy. however, % of niv patients ultimately received intubation. in our study, we found that the number of hfnc patients were much higher than niv patients when the hfnc or niv was used as an initial oxygen support. it means that physicians were more likely to use hfnc among the critically ill patients caused by ncip. as the outbreak of ncip in china, thousands of clinical staff joined in the patient management. most of them had no experience on how to use hfnc or niv. the current knowledge shows that ( ) the hfnc is non-inferior to niv on intubation rate in critically ill patients [ ] ; ( ) the use of hfnc is more comfortable than niv and the skin breakdown is less likely to occur [ , ] ; and ( ) the manipulation of hfnc is much easier than niv. therefore, the clinical staff were more likely to use hfnc in ncip patients. person-to-person transmission of ncip has been confirmed. in the early stages, the epidemic doubled in size every . days, and the estimated basic reproductive number was . ( % ci . to . ) [ ] . the virus is believed transmitted mostly via droplets or contact and possibly via aerosol [ ] . all people are generally susceptible to the virus. as of february , , clinical staff have been infected with ncip, and of them died [ ] . therefore, a device that produces lesser number of droplets or aerosol is required. the exhaled air dispersion produced by hfnc was limited and the risk of hospital-acquired infection did not increase [ , ] . therefore, the use of hfnc in ncip patients is feasible. however, the amount of condensation in the circuit increased when the ambient temperature decreased [ ] . the condensed water became an important source of infection for ncip. so, avoidance or reduction of condensation was very important when the hfnc was used. a previous study reported that % of hfnc patients required intubation [ ] . in this study, % of patients experienced hfnc failure and required niv as rescue therapy. among the niv patients who experienced hfnc failure, the intubation rate was %. however, in our study, % of patients experienced hfnc failure. among the unsuccessful patients, all of them directly switched to niv (no one directly switched to intubation). it means that the physicians who managed the ncip patients were more likely to use niv than intubation when the hfnc was unable to maintain the oxygenation. we speculated that the process of intubation made the physicians at high risk of infection because of the close encounter and irritable cough. however, among the patients with hfnc failure in our study, only % received intubation. this indicates that the success rate is high after transition to niv. our study has several limitations. this is a retrospective observational study. we did not predefine how to manage the hfnc. the transition to niv or intubation was decided by the attending physicians. different physicians have different opinions on the point to switch to niv or intubation. however, this study can reflect on how the hfnc has been used in the real world among the ncip patients. in addition, we only enrolled patients in this study as the enrollment period is short. to our knowledge, there are no studies that report on how the hfnc was used in ncip patients. rapid publication is very important for public health. it also can provide an important reference for clinical physicians when using hfnc in ncip patients. this study firstly reports the experience of how to use hfnc in patients with ncip. hfnc was the most common ventilation support for patients with ncip. patients with lower pao /fio were more likely to experience hfnc failure. the overall rate of intubation was % among the ncip patients with severe acute respiratory failure. abbreviations ncip: novel coronavirus ( -ncov)-infected pneumonia; hfnc: high-flow nasal cannula; niv: noninvasive ventilation; ards: acute respiratory distress syndrome; apache ii: acute physiology and chronic health evaluation ii; sofa: sequential organ failure assessment; rr: respiratory rate; hr: heart rate; sbp: systolic blood pressure; dbp: diastolic blood pressure; iqr: interquartile range. a pneumonia outbreak associated with a new coronavirus of probable bat origin clinical features of patients infected with novel coronavirus in wuhan epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster a familial cluster of infection associated with the novel coronavirus indicating potential person-to-person transmission during the incubation period first case of novel coronavirus in the united states the first case of novel coronavirus pneumonia imported into korea from wuhan, china: implication for infection prevention and control measures first imported case of novel coronavirus in canada, presenting as mild pneumonia first cases of coronavirus disease (covid- ) in france: surveillance, investigations and control measures novel coronavirus pneumonia emergency response epidemiology team. the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure respiratory care equipment. philadelphia: j.b. lippincott company high-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy but not to noninvasive mechanical ventilation on intubation rate: a systematic review and meta-analysis effect of high-flow nasal therapy on dyspnea, comfort, and respiratory rate high-flow nasal cannula therapy versus intermittent noninvasive ventilation in obese subjects after cardiothoracic surgery special expert group for control of the epidemic of novel coronavirus pneumonia of the chinese preventive medicine association. an update on the epidemiological characteristics of novel coronavirus pneumonia covid- exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks effect of high-flow nasal cannula oxygen therapy in immunocompromised subjects with acute respiratory failure. respir care inspiratory tube condensation during high-flow nasal cannula therapy: a bench study publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -m dy us authors: hraiech, sami; bourenne, jérémy; kuteifan, khaldoun; helms, julie; carvelli, julien; gainnier, marc; meziani, ferhat; papazian, laurent title: lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in sars-cov- -related acute respiratory distress syndrome date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: m dy us nan the current international outbreak of respiratory illness due to sars-cov- and named covid- can evolve to severe progressive pneumonia and acute respiratory distress syndrome (ards), multiorgan failure, and death. up to now, there are no specific therapeutic agents for coronavirus infections. lopinavir-ritonavir treatment recently failed to demonstrate any significant outcome benefit, but the study was underpowered to rule out clinically meaningful treatment effects, and the intervention was started a median of days after symptoms onset [ ] . in vitro inhibition of virus spread has been reported with chloroquine prior to or after sars-cov- infection [ ] . hydroxychloroquine has been found to be more potent than chloroquine to inhibit sars-cov- in vitro [ ] and a recent report suggested that % of non-icu hydroxychloroquine-treated patients had negative pcr results in nasopharyngeal samples at day (d ) post-inclusion [ ] and in all the patients treated with hydroxychloroquine and azithromycin combination (hydroxychloroquine-azithromycin) [ ] . in order to evaluate these results in intensive care unit (icu) patients, we retrospectively assessed in moderate-to-severe ards the efficacy of hydroxychloroquine-azithromycin combination regarding viral disappearance at both day of the treatment and day of evolution of ards as compared with patients treated with lopinavir-ritonavir and a control group without any anti-viral treatment. forty-five patients were included, receiving the combination of hydroxychloroquine mg and azithromycin then mg daily, receiving lopinavirritonavir mg daily and who did not receive any anti-viral treatment (controls). patients were admitted to icus in different regions of france from march nd to march st. in one icu, they received hydroxychloroquine-azithromycin as a usual policy while this combination was maintained if started prior to admission in the second icu (the other patients receiving lopinavir-ritonavir). controls were treated in other icus with antibiotics targeting bacterial community acquired pneumonia only. in all patients, nasopharyngeal pcr for sars-cov- were performed at the time of diagnosis and then regularly during icu stay in order to assess viral clearance. results of pcr were qualitative at the beginning of the pandemic, then quantitative and expressed by the pcr cycle threshold (ct). data were expressed as mean ± the standard deviation or median with interquartile range for the quantitative variables, and as numbers and percentages for the categorical variables. groups were compared using the chi-square or fisher's exact test for categorical characteristics, and using the student's t test or mann-whitney u test for continuous ones. a two-sided p value of less than . was considered statistically significant. results are displayed in table . patients presented ards criteria ± days after diagnosis confirmation and open access *correspondence: sami.hraiech@ap-hm.fr ± days after treatment onset. negative nasopharyngeal pcr for sars-cov- at day following the initiation of treatment were observed in ( %) patients from the lopinavir-ritonavir group as compared with ( %) patients from the hydroxychloroquine-azithromycin group and ( %) from the control group (p = . ). at day following ards onset, pcr was negative in only patients, from the lopinavir-ritonavir group, from the hydroxychloroquine-azithromycin group and from the control group. when considering only the patients that had received an anti-viral treatment within the days following the onset of covid- symptoms, we found that none of them ( / ) had a negative pcr days after the beginning of treatment in the hydroxychloroquineazithromycin group as compared with / ( %) in the lopinavir-ritonavir group (p = . ). at day following ards, mortality was . %, all survivors being under mechanical ventilation (mv) with no difference regarding ventilatory parameters, use of adjuvants and sofa score. the latest follow-up done ± days following treatment onset revealed that patients were still alive ( %), ( %) in the lopinavir-ritonavir group, ( %) in the hydroxychloroquine-azithromycin group and ( %) in the control group. ten patients were still in icu, ( %) from the hydroxychloroquine-azithromycin group, and ( %) from the lopinavir-ritonavir group. in this case-control study, the rates of viral clearance at day after treatment were not significantly different between patients treated with hydroxychloroquine and azithromycin, patients treated with lopinavir-ritonavir and those not treated with any specific anti-viral treatment. no difference in sars-cov- pcr negativity was found between groups days after meeting moderate-tosevere ards criteria. groups were comparable, except for a higher severity at admission in control patients, who were more frequently transferred to the icu only when requiring mv, because of the massive influx of patients in this region of france. although a positive pcr is not synonymous with active viral development, these results highlight the fact that neither of the treatments was able to achieve a rapid viral clearance in ards patients, as it has been suggested in one report on non-severe patients [ ] . waiting for the results of ongoing randomized controlled trials, clinicians should prescribe these treatments taking into account the paucity of the current rationale and the risk-benefit ratio in severe forms. moreover, considering the lack of viral clearance in the most severe patients, the use of immunosuppressive drugs should be carefully balanced in this population [ ] . a trial of lopinavir-ritonavir in adults hospitalized with severe covid- chloroquine is a potent inhibitor of sars coronavirus infection and spread in vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus (sars-cov- ) hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial immunosuppression for hyperinflammation in covid- : a double-edged sword? lancet publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we acknowledge all the medical and nurse staff of the medical icu of marseilles north hospital. authors' contributions sh, jb, jh, kk, collected and analysed the data. sh, jc and jb performed the statistical analysis. sh, lp, fm and mg wrote the manuscript. all authors read and approved the final manuscript. the authors received no funding for this work. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. patients and their relatives were informed of the possibility of the use of medical data for retrospective studies and did not manifest opposition. not applicable. the authors declare that they have no competing interests. key: cord- -xaehtmjf authors: roesthuis, l. h.; van der hoeven, j. g.; van hees, h. w. h.; schellekens, w.-j. m.; doorduin, j.; heunks, l. m. a. title: recruitment pattern of the diaphragm and extradiaphragmatic inspiratory muscles in response to different levels of pressure support date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: xaehtmjf background: inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. this provides a good rationale to monitor respiratory drive in ventilated patients. respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. a disadvantage is that both techniques are invasive. therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. the aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm. methods: activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. pressure support (ps) levels were reduced from to cmh( )o every min with steps of cmh( )o. the magnitude and timing of respiratory muscle activity were assessed. results: we included ventilated patients. diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower ps levels ( ± % increase for the diaphragm, ± % parasternal intercostals, ± % scalene, ± % sternocleidomastoid, ± % alae nasi and ± % genioglossus). changes in diaphragm activity correlated best with changes in alae nasi activity (r( ) = . ; p < . ), while there was no correlation between diaphragm and sternocleidomastoid activity. the agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. onset of alae nasi activity preceded the onset of all other muscles. conclusions: extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. however, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (emg) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm. background diaphragm dysfunction frequently develops in critically ill patients [ ] [ ] [ ] . among other factors, inappropriate ventilator assist plays a prominent role in the pathogenesis. ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy [ ] [ ] [ ] [ ] [ ] [ ] . this provides a good rationale to monitor respiratory effort in ventilated intensive care unit (icu) patients [ ] [ ] [ ] [ ] . calculation of muscular pressure (pmus) based on changes in esophageal pressure and chest wall elastic recoil pressure is considered the gold standard to monitor respiratory effort [ , ] . electrical activity of the diaphragm (eadi), acquired with a nasogastric catheter with multiple electrodes, has been used to quantify respiratory effort as well [ ] [ ] [ ] . although electromyography (emg) does not directly reflect effort, a linear correlation between pmus and eadi has been reported [ ] . however, both techniques are invasive and the multi-electrode esophageal catheter is only available with one specific ventilator (servo-i/u). however, eadi can also be obtained using surface electrodes [ , ] , although with specific challenges, especially in obese patients, or after abdominal surgery. therefore, it is of interest to investigate surrogate markers for respiratory drive, such as activity of extradiaphragmatic inspiratory muscles [ ] . the extradiaphragmatic inspiratory muscles support the diaphragm to maintain adequate ventilation, but each muscle has specific other tasks. for instance, the alae nasi and genioglossus maintain upper airway patency [ ] [ ] [ ] , the parasternal intercostals stabilize the chest wall and facilitate rotation of the trunk [ , ] , while the scalene and sternocleidomastoid are involved in rotation of the head and flexion of the neck [ ] . in previous studies, surface emg has been used in ventilated icu patients to evaluate activity of the extradiaphragmatic inspiratory muscles, including alae nasi, parasternal intercostals [ ] , scalene [ , ] , sternocleidomastoid and genioglossus [ ] [ ] [ ] . overall, these papers concluded that monitoring of respiratory drive in ventilated icu patients by surface emg is feasible and useful. however, the effect of different levels of ventilator support on the relation between diaphragmatic and extradiaphragmatic inspiratory muscle activity was not studied in detail, as well as a comparison on individual patient level between activity of the diaphragm and extradiaphragmatic inspiratory muscles. therefore, the aim of the current study is to investigate in invasively ventilated icu patients the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm in response to different inspiratory support levels and to evaluate agreement between activity of the extradiaphragmatic inspiratory muscles and the diaphragm. this study was conducted in a mixed icu of the radboud university medical center. adult patients mechanically ventilated for at least days, with a nava catheter (maquet critical care, sölna, sweden) in situ and inspiratory support ≤ cmh o, positive end-expiratory pressure (peep) level ≤ cmh o and fio < . , were recruited. exclusion criteria were hemodynamic instability [i.e. systolic blood pressure < mmhg; heart rate < or > beats/min and use of high-dose vasopressors (i.e. norepinephrine > . µg/kg/min)]. based on previous physiological studies from our group [ ] [ ] [ ] [ ] , a convenience sample of patients was considered appropriate. the institutional review board waived informed consent as risks associated with this study were negligible. patients or patient surrogate decision-makers were informed about the study purpose and design. this was a prospective clinical study. all patients were ventilated with a servo-i ventilator (maquet critical care, sölna, sweden). activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was continuously measured as described below. pressure support (ps) level was reduced every min with steps of cmh o, from cmh o to cmh o. the duration of min for each study step was considered appropriate as it has been shown previously that respiratory drive adapts within min of altered loading [ , , ] . peep, inspiratory rise time, cycle-off criteria and trigger sensitivity were maintained as dictated by clinical protocol. flow was acquired by placing a single use flow sensor (hamilton medical ag, bonaduz, switzerland) between the endotracheal tube and y-piece of the ventilator circuit, connected to a pressure transducer (range ± kpa, freescale semiconductor, tempe, az, usa). the pressure transducer was connected to the auxiliary channel ( . μv/bit, amplification factor: ) of the porti data acquisition system ( bits, tmsi; the netherlands). keywords: ventilated critically ill patients, respiratory drive, electrical activity of the diaphragm, extradiaphragmatic inspiratory muscle activity, surface electromyography eadi was obtained using a multi-electrode nasogastric catheter. correct positioning of the catheter was obtained using standard software supplied with the ventilator by the manufacturer. electrical activity from the extradiaphragmatic muscles was recorded using wet gel silver-silverchloride surface electrodes, × mm in diameter (ambu ® blue sensor n, ballerup, denmark). recording locations were cleaned to improve signal to noise ratio. for the alae nasi, electrodes were placed on each side of the nose. for the genioglossus electrodes were placed just below the chin and above the hyoid bone. electrode placement of the sternocleidomastoid and scalene was guided by ultrasonography and electrodes were placed in the lower thirds of the muscles [ ] . for the parasternal intercostals, the active electrode was placed in the second intercostal space cm lateral from the sternum and the reference on an adjacent rib. a ground electrode was placed on the patient's wrist. visual feedback for all (emg) signals was available. eadi was acquired with a porti data acquisition system ( bits, tmsi; the netherlands) with unipolar electrophysiological channels ( . nv/bit, amplification factor: ). emg from extradiaphragmatic muscles was acquired with a porti data acquisition system ( bits, tmsi; the netherlands) with bipolar electrophysiological channels ( . nv/bit, amplification factor: ). flow and emg signals were digitized with a sample frequency of hz and stored synchronously on a hard disk using portilab (tmsi; the netherlands). offline analysis was performed with matlab (r b, the mathworks, natick, massachusetts, usa). eadi was processed as described previously [ ] . surface emg signals were band-pass filtered using a - hz second-order butterworth filter. if present, ecg artifacts were removed from the emg using a wavelet-based adaptive filter [ ] . from each recording (i.e. from every muscle and ps level) at least breaths free of artifacts were selected at the end of each period. for each period the root mean square of the emg was determined with a time averaging period of ms. further smoothing was obtained by applying a moving average filter with a window size of ms to obtain a mean emg envelope. an example of processing of the emg signal is given in additional file : figure s . inspiratory efforts were detected from the flow signal and segmented in epochs time-locked to the inspiratory efforts. these epochs started s before the inspiratory effort and terminated . s after the onset of the inspiratory effort [ ] . respiratory rate, tidal volume, minute ventilation and inspiratory time were calculated from the flow signal. a threshold was determined visually from the mean emg envelops to detect onset, peak and end of muscle activity (additional file : figure s ). the maximal amplitude of muscle activity during inspiration was defined as emg peak . in addition, area under the curve of muscle emg activity was calculated from onset of muscle activity till muscle activity was reduced to % of emg peak , multiplied with respiratory rate (emg auc/min ). both parameters were normalized to muscle activity at pressure support level cmh o (% ps ). timing of onset, peak and end of muscle activity were calculated relatively to the onset time of eadi (additional file : figure s ). to compare the magnitude and timing of respiratory muscle activity between ps levels, one-way analysis of variance for repeated measures was performed (friedman test). post-hoc analysis was performed with dunn's multiple comparison test, to correct for multiple comparisons. repeated observation analysis was performed to investigate whether changes in diaphragm activity would also result in the same changes in extradiaphragmatic inspiratory muscle activity [ ] . eadi and surface emg for each of the extradiaphragmatic inspiratory muscles were compared using bland-altman analysis. for all tests, a two-tailed p < . was considered significant. data are presented as mean ± standard error of the mean (sem) for parametric data or median (interquartile range) for non-parametric data. statistical analyses were performed with prism (graphpad software, san diego, ca, usa). seventeen patients with a nava catheter for clinical reasons were consecutively enrolled. mean body mass index was . ± . kg/m . other patient characteristics are shown in table . no adverse events were reported during the study. reducing inspiratory ps level increased respiratory frequency, and decreased tidal volume and minute ventilation (table ) . ps level did not affect inspiratory time ( table ). as expected, eadi peak increased while lowering ps level (fig. ) . in general, the extradiaphragmatic inspiratory muscles emg peak followed a similar pattern (fig. ) , although the responses varied strongly among muscles and patients (additional file : figure s ). emg auc/min provided similar results (additional file : figure s ). in several patients, extradiaphragmatic inspiratory muscle activity could not be detected: alae nasi (n = ), genioglossus (n = ), scalene (n = ) and parasternal intercostal muscles (n = ). calculation of correlation coefficients with repeated observations showed the highest positive correlation between eadi peak and alae nasi emg peak (r = . ; p < . ), with emg peak expressed as percentage relative to ps cmh o. this was followed by the parasternal intercostals emg peak (r = . ; p < . ) and genioglossus emg peak (r = . ; p < . ). a poor correlation was found between eadi peak and scalene emg peak (r = . ; p < . ), whereas no correlation was found between eadi peak and sternocleidomastoid emg peak . on individual patient level, large differences were observed between the changes in diaphragm and extradiaphragmatic inspiratory muscle activity (fig. ). bland-altman analyses (additional file : figure s ) showed that the bias between eadi and surface emg for each of the extradiaphragmatic inspiratory muscles is small; however, the % limits of agreement are large due to individual differences. regardless of the level of support the limits of agreement remain large. figure shows the recruitment hierarchy of the diaphragm and extradiaphragmatic inspiratory muscles. timing is relative to the onset of eadi. data were averaged per muscle for the different levels of support, because timing was not affected by the level of support. onset of alae nasi activity preceded the onset of all other muscles. both peak and termination of electrical activity occurred earlier for both the alae nasi and genioglossus compared to the other muscles. in addition, parasternal intercostal activity terminated earlier than sternocleidomastoid, eadi and scalene activity. the main finding of the current study is that surface emg of extradiaphragmatic inspiratory muscles does not reliably reflect activity of the diaphragm under different levels of inspiratory support. there is a moderate to low correlation and low agreement between changes in diaphragm and extradiaphragmatic inspiratory muscle activity in response to unloading of the respiratory muscles. furthermore, there are notable differences in timing of activation between the diaphragm and extradiaphragmatic inspiratory muscles. as expected, activity of the extradiaphragmatic inspiratory muscles increased in response to reducing level of assist on a group level. our results are largely in accordance with previous studies in intubated patients. schmidt et al. reported that parasternal intercostal, scalene and alae nasi activity increases when a low inspiratory ps level is applied as compared to a high ps level [ ] . cecchini et al. [ ] showed that both nava and ps ventilation reduced alae nasi and scalene activity in proportion to the level of assistance. in addition, we found that this also holds for the genioglossus, despite that the endotracheal tube bypasses the upper airways. remarkably, in most patients extradiaphragmatic inspiratory muscles remain active up to a ps level of cmh o. brochard et al. [ ] also demonstrated that the sternocleodomastoid muscle remains active at high inspiratory ps levels. these findings indicate high respiratory drive even at high levels of pressure support. high respiratory drive despite high levels of inspiratory assist may be explained by persistent abnormal arterial blood gas, feedback from afferents from the lung and chest wall or systemic inflammation (for review see [ ] ). in the current study, we showed with repeated measures observation analysis that there are only moderate correlations between the changes in diaphragm and extradiaphragmatic inspiratory muscle activity (fig. ) . moreover, we demonstrate that there are large limits of agreement for all ps levels when comparing the changes in diaphragm and extradiaphragmatic inspiratory muscle activity (additional file : figure s ). for example, for the scalene and diaphragm, the % limits of agreement are between - and + % ps (normalized to muscle activity at ps level cmh o) for changes in surface emg and eadi peak (additional file : figure s ). in clinical practice, such a measurement error is unacceptable, because this means, for example at an average eadi peak of % ps (normalized to muscle activity at ps level cmh o) at ps , that there could be either no scalene activity or scalene emg peak could be doubled. the relationship between diaphragm and extradiaphragmatic inspiratory muscle activity has been addressed previously. these studies reported that the recruitment pattern of extradiaphragmatic inspiratory muscles is comparable to the diaphragm in response to lower inspiratory support levels during noninvasive ventilation in healthy subjects [ , , ] , patients with chronic obstructive pulmonary disease (copd) [ ] and ventilated icu patients [ , ] . in contrast to our study, no correlation or agreement analysis were reported in most of these studies. in the study by lin et al., there were also large limits of agreement between diaphragm and scalene muscle activity during noninvasive ventilation in copd patients, whereas the parasternal intercostal muscles performed better [ ] . copd patients often have high levels of neural respiratory drive (for review see [ ] ) and thereby extradiaphragmatic inspiratory muscle activity is easier to detect with surface emg. eadi peak (% ps ) fig. relation between diaphragm and extradiaphragmatic inspiratory muscle activity for pressure support (ps) level , , and cmh o, with peak electrical activity of the diaphragm (eadi peak ) and peak electromyography (emg peak ) normalized to muscle activity at ps level cmh o (% ps ). each individual patient is depicted in a specific color and marker. the regression lines describing the relation on individual patient level are depicted, from which the high variability among patients is clear. points are not shown (ps patient for scalene (scalene emg peak % ps at eadi peak % ps ) and ps and patient for sternocleidomastoid (sternocleidomastoid emg peak and % ps at eadi peak and % ps , respectively), as values were off scale. however, the regression lines shown include these data points taken together, reducing inspiratory assist does not have a uniform effect on the diaphragm and extradiaphragmatic inspiratory muscles. differences in responses among muscles may be partly explained by the fact that extradiaphragmatic inspiratory muscles are involved in other functions, such as patency of the upper airways, rotation of the head, flexion of the neck and stabilization of the trunk [ ] [ ] [ ] [ ] [ ] [ ] . for the parasternal intercostal muscles the same motoneurons are depolarized during postural and inspiratory tasks; their output during inspiration is depending on the direction of the rotation of the trunk [ ] . furthermore, it has been shown that neural respiratory drive is not uniform in healthy subjects, and respiratory muscles recruit according to their mechanical advantage. in other words, respiratory muscles (or portions of muscles) with the greatest mechanical advantage for a specific task will be recruited earlier and to a larger extent [ , ] . it seems plausible that the same is true in disease, which could result in differences in recruitment of extradiaphragmatic inspiratory muscles and the diaphragm with changes in ventilator support. parthasarathy et al. [ ] suggested such a hierarchy of respiratory muscle recruitment in patients failing a t-piece trial. in addition to the diaphragm and intercostal muscles, they demonstrated an immediate increase in sternocleidomastoid muscle activity with little change thereafter. the expiratory muscles are recruited relatively late during the t-piece trial: the largest increase in activity occurred only after - min. finally, drive to the diaphragm may underestimate the true respiratory drive due to the contribution of the extradiaphragmatic inspiratory muscles, especially in critically ill patients there may be a discrepancy. respiratory drive can be higher in critically ill patients not only due to the load on the respiratory muscles, but also due to metabolic acidosis and hypoxemia, brain, lung or chest wall pathologies (for review see [ ] ). in healthy subjects there is a clear hierarchy with respect to respiratory muscle recruitment [ , ] . for example, upper airway muscles recruit ± ms before the diaphragm recruits in healthy subjects [ ] . we studied more different muscles and applied different ps levels as compared to previous studies [ , ] . the alae nasi recruited earlier as compared to other extradiaphragmatic inspiratory muscles ( - ms) and the diaphragm ( ms). we found no differences in timing of the extradiaphragmatic inspiratory muscles between ventilator settings. these results were expected based on previous studies [ , ] . schmidt et al. [ ] observed that recruitment onset times were similar among the scalene, sternocleidomastoid and genioglossus in mechanically ventilated patients. in addition to the poor correlations and low agreement between changes in activity between the diaphragm and extradiaphragmatic inspiratory muscles in response to unloading, there are practical issues that limit the applicability of surface emg to monitor drive to the diaphragm. first, we found that in several patients no muscle activity could be detected from the genioglossus, alae nasi, parasternal intercostals and scalene during the whole study protocol. this could be the result from real inactivity of the muscles or low signal-to-noise ratio. second, surface emg is vulnerable to noise (e.g. electromagnetic noise) and artifacts (e.g. due to movement), these cannot be avoided, but the effects can be minimized in the preprocessing and analyzing process [ ] . third, the technique is technically challenging in obese patients, restless patients, or patients with diaphoresis. note that data used in the current study were highly selected. large periods of data were not useful to study breathing activity because patients were moving their head or body resulting in non-breathing-related muscle activity. the current study has some limitations. first, we did not measure force, only emg as a measure for respiratory drive. respiratory drive can be evaluated at the bedside by several methods (for recent review see [ ] ). the only method to measure the contribution of extradiaphragmatic inspiratory muscles to respiration is by surface emg. therefore, we wanted to evaluate the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm. second, we did not measure surface eadi. bellani et al. [ ] demonstrated that surface eadi correlated well with eadi, although there was a high variability in the slopes between patients. they showed that respiratory effort could be calculated from surface eadi, but when comparing surface eadi with esophageal pressure to compute muscular pressure, this resulted in low bias but large limits of agreement. calculation of effort from both the diaphragm and extradiaphragmatic inspiratory muscles did not result in an improved estimation of respiratory effort as compared to eadi or surface eadi. third, the study was not blinded. the signals were analyzed offline, only periods to be analyzed were selected manually, while the rest of the analysis was performed automatically using a custom-written script. therefore, the unblinded nature is unlikely to affect the results. fourth, accuracy of calculating recruitment times depends on the manner in which the threshold for muscle activity is determined, and also on the noise level. therefore, not only relative onset times were computed, but also peak and termination times. for all three parameters the same trends were found and recruitment times were in the same range. in the current study, we investigated potential surrogate markers of diaphragm activity. we demonstrate that extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. however, we found moderate correlations and low agreement between changes in diaphragm activity and extradiaphragmatic inspiratory muscle activity. therefore, it is concluded that monitoring of respiratory drive is not feasible using extradiaphragmatic inspiratory muscle activity. we demonstrate that the magnitude and timing of muscle activity differ among inspiratory muscles, making it very cumbersome to monitor patient-ventilator interactions. critical illness-associated diaphragm weakness diaphragm muscle fiber weakness and ubiquitinproteasome activation in critically ill patients rapidly progressive 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muscle coordination be precisely studied by surface electromyography? publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations not applicable. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . study conceptions and design: lhr, jd, lmah; data acquisition: lhr, jd; data analysis: lhr, jd, lmah; data interpretation: all authors; manuscript drafting and revising: all authors. all authors read and approved the final manuscript. there was no financial funding for this study. the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. the study protocol was approved by the local ethical committee (cmo regio arnhem-nijmegen) and informed consent was waived as potential risks associated with this study were negligible. not applicable. the authors declare that they have no competing interests. key: cord- -vt e crh authors: elabbadi, alexandre; pichon, jérémie; visseaux, benoit; schnuriger, aurélie; bouadma, lila; philippot, quentin; patrier, juliette; labbé, vincent; ruckly, stéphane; fartoukh, muriel; timsit, jean-françois; voiriot, guillaume title: respiratory virus-associated infections in hiv-infected adults admitted to the intensive care unit for acute respiratory failure: a -year bicenter retrospective study (hiv-vir study) date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: vt e crh introduction: acute respiratory failure is the main reason for admission to the intensive care unit (icu) in hiv-infected adults. there is little data about the epidemiology of respiratory viruses in this population. methods: hiv-infected adults admitted to two intensive care units over a -year period for an acute respiratory failure and explored for respiratory viruses with multiplex polymerase chain reaction (mpcr) were retrospectively selected. objectives were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome. results: a total of episodes were included. an hiv infection was newly diagnosed in % of cases and % of the population were on antiretroviral therapy. real-time mpcr tests identified at least one respiratory virus in the respiratory tract of ( %) patients, but with a non-viral copathogen in two-thirds of cases. rhinovirus was predominant, documented in patients, followed by influenza and respiratory syncytial viruses (both n = ). the prevalence of respiratory virus-associated infection did not vary along with the level of the cd t-cell deficiency, except for rhinovirus which was more prevalent in patients with a cd lymphocyte count below cells/µl (n = ( %) vs. n = ( %), p < . ). in multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis. conclusions: viruses are frequently identified in the respiratory tract of hiv-infected patients with acute respiratory failure that requires icu admission, but with a non-viral copathogen in two-thirds of cases. rhinovirus is the predominant viral specie; its prevalence is highest in patients with a cd lymphocyte count below cells/µl. acute respiratory failure (arf) is the leading cause of admission to the intensive care unit (icu) in hivinfected patients [ ] [ ] [ ] . infectious causes are predominant, although the proportion of opportunistic infections has decreased significantly in the era of combination antiretroviral therapy (art) [ , , ] . in contrast, the open access *correspondence: guillaume.voiriot@aphp.fr assistance publique -hôpitaux de paris, service de médecine intensive réanimation, hôpital tenon, sorbonne université, paris, france full list of author information is available at the end of the article burden of non-hiv-related pulmonary events, such as bacterial pneumonia, acute bronchitis and acute exacerbation of chronic obstructive pulmonary disease (copd) has been shown increasing [ , , ] . these important changes in the etiologic panel of arf in hiv-infected patients question the role of respiratory viruses. indeed, using nucleic acid amplification test such as multiplex polymerase chain reaction (mpcr), these pathogens have been shown highly prevalent ( - %) in large cohorts of adult patients admitted to the icu for all-cause arf [ , ] , community-acquired pneumonia [ , ] , hospitalacquired pneumonia [ ] , acute exacerbation of copd [ , ] , and asthma [ ] , compared to asymptomatic adults [ , ] . high prevalence has also been described in specific immunocompromised populations, such as cancer and hematology patients [ , ] . in contrast, little is known about the epidemiology of respiratory viruses in hiv-infected patients [ , ] , especially those admitted to the icu, and the prevalence of respiratory viruses according to the cd t-cell deficiency. moreover, coinfections with virus and opportunistic pathogens may occur. overall, respiratory virus-associated infections may affect prognosis. therefore, we conducted a comprehensive observational study among adult hiv-infected icu patients with arf explored with respiratory mpcr. our goals were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome. we conducted a retrospective bicenter observational study in two icu of the paris area (the -bed icu of the bichat university hospital and the -bed icu of the tenon university hospital). from april to april , all consecutive hiv-infected patients admitted to icu having undergone an mpcr in the respiratory tract within h following their icu admission were screened. medical records were independently reviewed by two physicians (ae and gv). all patients with arf at icu admission were included. arf was defined by the presence of at least two of the following criteria: cough, expectoration, dyspnea, rales, signs of respiratory distress (tachypnea exceeding /min, paradoxical abdominal breathing), chest pain, hypoxemia requiring oxygen therapy, noninvasive ventilation or intubation. in case of multiple admissions over the -year study period, only the first admission was analyzed. at icu admission and during icu stay, data regarding demographics, comorbidity, hiv-related characteristics, clinical examinations, laboratory and radiological findings, microbiologic investigations, and therapeutic management were collected (for details, see additional file ). mortality was defined as death from any cause within days following the icu admission. respiratory mpcrs were performed either in nasopharyngeal (np) swabs or in lower respiratory tract (lrt) specimen, usually bronchoalveolar lavage (bal) fluid otherwise endotracheal aspirate. during the study period, different respiratory mpcr kits (additional file : table s ) were used (for more details about microbiological evaluation, see additional file ). medical charts were independently reviewed by two clinicians (ae and gv). they determined the causative diagnosis of arf for each patient, using a -class classification. in case of an inter-reviewer discordance, a shared review of the medical charts was performed, and an agreement was found. the five mutually exclusive classes of causative diagnosis for arf were: (i) pneumocystis jirovecii pneumonia (pcp); (ii) other opportunistic lung infections; (iii) non-opportunistic acute lung infection; (iv) non-infectious lung disease, and (v) extra-pulmonary cause (for details, see additional file ). the primary endpoint was to determine the prevalence of respiratory viruses according to the cd lymphocyte count. a respiratory virus documented with mpcr was always considered as a pathogen of the respiratory tract, regardless of the type of specimen (np or lrt). the cd lymphocyte count measured during the icu stay was used to group patients, with a cut-off of cells/µl (≤ cells/µl for the low-cd group; > cells/µl for the high-cd group) [ , ] . secondary endpoints were to describe the epidemiology of respiratory viruses and coinfections with non-viral pathogens, to identify risk factors for respiratory virusassociated infection, and to study outcome. a composite criterion named "complicated course" included death from any cause within days following the icu admission or mechanical ventilation for more than days. continuous data were expressed as median [first through third quartiles] and were compared using the pairwise mann and whitney test. categorical data were expressed as number (percentage) and were evaluated using the chi-square test or fisher exact test. p values less than . were considered significant. a univariate logistic regression with clinically relevant variables was used to identify variables associated with a respiratory virusassociated infection. a multivariate conditional logistic regression, including variables with p value less than . in the previous step, was used to identify variables independently associated with a respiratory virus-associated infection. similar statistical analyses were performed to identify variables independently associated with death from any cause within days following the icu admission and mechanical ventilation for more than days in survivors at day- . quantitative variables that did not validate the log-linearity assumption were transformed into categorical variables according to their median value. missing data were imputed to the median or the more frequent value. the accuracy of the final model was tested using area under the receiver operating characteristic curve analysis and the hosmer-lemeshow chi-square test. analyses were performed using the sas software package (sas institute, cary, nc, usa). during the -year study period, hiv-infected adult patients were admitted at least once to icu and underwent a respiratory mpcr in the first h of the icu stay. among them, did not fulfill criteria of arf. the final study group consisted of patients. their main characteristics, stratified by the cd lymphocyte count at icu admission, are presented in table . of these patients, were admitted twice during the study period and one was admitted thrice. eleven patients ( %) were newly diagnosed as having hiv infection on icu admission; the remaining had been previously diagnosed, and were on art but with poor adherence to the treatment in patients, as mentioned by the infectiologist in the medical charts. latest available median cd lymphocyte count and hiv viral load were cells/µl [ - ] and log copies/ml [ - . ], respectively. at least one additional factor of immunosuppression was identified in ( %) patients. at icu admission, median cd lymphocyte count was cells/µl , with patients ( %) equal or below cells/µl (low-cd group) and ( %) above cells/µl (high-cd group). both these groups did not differ regarding demographics, performance status, factors of immunosuppression other than hiv and comorbidity, except for copd which was more prevalent in the high-cd group (n = ( %) vs. n = ( %), p = . ). the microbiological investigations are displayed in additional file : table s . mpcr was performed in np swabs exclusively (n = , %) or in lrt specimen exclusively (n = , %), or both (n = , %). respiratory tract specimens for bacterial culture have been obtained in ( %) patients. bal fluid has been obtained in ( %) patients. causative diagnoses of arf are displayed in table . an opportunistic lung infection was diagnosed in ( %) patients. seven of the patients with newly diagnosed hiv infection and patients receiving art, but with a poor adherence to the treatment had pcp. non-opportunistic acute lung infections were identified as causative diagnosis of arf in ( %) patients. all the bacteria-infected patients received an appropriate antimicrobial regimen within the first h of icu stay. eight patients had a clinical presentation suggestive of lung infection, but without microbiological documentation. the arf was attributed to a non-infectious lung disease in ( %) patients, mainly related to a decompensated chronic condition, i.e., acute exacerbation of copd and pulmonary edema. overall, respiratory viruses were identified in ( %) patients (table ) . rhinovirus was predominant (n = ), followed by influenza (n = ), respiratory syncytial virus (n = ) and parainfluenza virus (n = ). only one pure virus-virus coinfection was found. the prevalence of respiratory virus-associated infection did not differ among low-and high-cd groups (table ) ; therefore, the median cd lymphocyte count in respiratory virus-infected patients was cells/µl, in comparison with cells/µl in non-infected patients (fig. ) . however, the prevalence of rhinovirus-associated infection was higher in the low-cd group, and three-quarters of rhinovirus-infected patients exhibited a cd lymphocyte count below cells/µl (fig. ) . in patients, the viral documentation was accompanied by a non-viral documentation (additional file : figure s ), with bacteria-virus coinfection in patients, bacteria-virus-virus in patients, p. jirovecii-virus in patients and p. jirovecii-virus-virus in one patient. the rate of viral documentation among patients explored with np swab exclusively, lrt specimen exclusively, or both, did not differ significantly ( %, % and %, respectively; p = . ). documentation of respiratory viruses was more frequent during the winter period (october to march) (additional file : figure s ). conversely, rhinovirus documentation did not follow a seasonal distribution, since only / were observed during the period from october to march. characteristics of the population, stratified by respiratory virus-associated infection are presented in additional file : table s . at icu admission, respiratory virus-infected patients displayed higher respiratory rate and fever. in multivariate analysis, female gender, smoking and steroid therapy were shown as independently associated with respiratory virus-associated infection ( table ) . mortality at day- was %, and % of patients displayed a complicated course, without difference between high-cd and low-cd groups (table ) . we investigated whether a respiratory virus-associated infection table causative diagnosis of acute respiratory failure in hiv-infected patients admitted to the icu data are presented as number (%). cd refers to cd lymphocyte count (cells/µl) a other opportunistic lung infections included cmv-associated pneumonia (n = ) and pulmonary tuberculosis (n = ) b non-infectious lung diseases included acute exacerbation of copd of non-infectious etiology (n = ), cardiogenic lung edema without underlying lung agent (n = ), cryptogenic hemoptysis (n = ), intra-alveolar hemorrhage (n = ); acute interstitial pneumonia (n = ), mendelson syndrome (n = ), sickle cell disease (acute chest syndrome) (n = ); neoplastic pleural effusion (n = ) and castleman disease (n = ) c extra-pulmonary causes included histoplasmosis (n = ), cryptococcus neoformans meningitis (n = ), bacterial meningitis (n = ), pyelonephritis (n = ) and bacteremia of unknown origin (n = ) all extra-pulmonary cause c ( . ) ( . ) ( . ) affected prognosis. in the analysis stratified by respiratory virus-associated infection, outcome was similar between infected and non-infected patients (additional file : table s ). in multivariate analysis, a respiratory virus-associated infection was not identified as an independent factor of either a complicated course (table ) or death at day- (additional file : table s ). this retrospective study investigated the epidemiology of respiratory viruses in hiv-infected adults admitted to the icu for arf. real-time mpcr tests identified at least one virus in the respiratory tract of % of patients, but with a non-viral copathogen in two-thirds of cases. the prevalence of respiratory virus-associated infection did not vary along with the level of the cd t-cell deficiency, except for rhinovirus which was more prevalent in patients with a cd lymphocyte count below cells/ µl. in multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis. in this study, more than one patient out of four ( %) were infected with at least one respiratory virus. this finding illustrated the high yield of an aggressive diagnostic strategy with a broad panel mpcr on respiratory tract specimens. our results are original since prior works having described the etiological panel of arf in hivinfected icu patients were conducted before the era of real-time mpcr [ , , ] . interestingly, the rate of viral documentation that we observed was similar to what had been described ( to %) previously in non-hiv adults admitted to the icu for an acute respiratory disorder requiring intubation [ , ] . we identified at least one non-viral copathogen in more than two-thirds of the patients with a viral documentation, in line with a recent report in a population with a high prevalence of tuberculosis [ , ] . nonopportunistic acute lung infections, including pneumonia, acute bronchitis and exacerbation of copd, were the first cause of arf, consistent with previous reports in western countries [ , ] . this finding highlights the burden of chronic respiratory conditions in aging hivinfected populations [ ] . here, more than % of patients were smokers. synergistic effects of tobacco and hiv [ ] in promoting chronic bronchitis and pro-copd changes in the lung [ ] have been demonstrated. moreover, high rates of viral documentation within airways of copd patients both at stable state and during exacerbation have been reported [ ] . these data may explain the high rate of viral documentation that we observed. in multivariate analysis, smoking was independently associated with respiratory virus-associated infection. this finding is in line with previous works demonstrating that tobacco exposure alters immune responses to rhinovirus [ ] , influenza virus [ ] and respiratory syncytial virus [ ] . interestingly, female gender was associated with an increased risk of respiratory virus-associated infection on multivariate analysis. prior cohort studies in primary care described an increased risk for development of influenza-like illnesses in women compared to men [ , ] . however, to our knowledge, no prior study has specifically explored this point in hiv-infected populations admitted for arf. in this study, we also aimed to investigate a putative role of the hiv-related cd t-cell deficiency in promoting respiratory virus-associated infection. previous studies explored this point in children, but with conflicting results. annamalay et al. described similar rates of viral documentation in hiv-infected and non-infected children admitted for lower respiratory tract infections [ ] , whereas o'callaghan-gordo et al. observed that respiratory virus-associated infections were to times more prevalent among hiv-infected children admitted for pneumonia [ ] . as we did not include a comparative non-hiv population, we rather examined whether or not the rate of viral documentation varied along with the level of cd t-cell deficiency. finally, we found no association between the cd lymphocyte count and the risk of respiratory virus-associated infection, in line with a previous report focusing on influenza viruses [ ] . rhinovirus was the predominant virus, accounting for more than % of viral documentations. this high prevalence was consistent with that of previous reports in icu patients with arf [ ] , community-acquired pneumonia [ ] or acute exacerbation of copd [ ] . surprisingly, rhinovirus was much more prevalent in low-cd patients. this finding is original, since no prior work has specifically explored this point in adults. in hiv-infected children, rhinovirus has been shown highly prevalent, during both pneumonia and bronchiolitis, but without data regarding a putative association with the level of cd t-cell deficiency [ , ] . other data in hematology and cancer adults demonstrated high rates of rhinovirus documentation within airways during respiratory tract infections [ , ] . to explain this high prevalence in immunocompromised patients, a mechanism of prolonged viral shedding has been proposed, rather than iterative reinfections as observed in copd patients [ ] . the prolonged rhinovirus shedding may be attributable to an inefficient immunological control of a single infectious episode [ , ] . therefore, in pediatric hematopoietic stem cell transplant recipients with a persistent rhinovirus shedding (≥ days), piralla et al. demonstrated significant lower cd , cd and nk lymphocyte counts at the onset of infection, as compared to children with a brief rhinovirus shedding. moreover, a decrease in rhinovirus load was associated with significant increases of the same lymphocyte counts [ ] . these data would suggest an important role for the t-cell immunity in the control of rhinovirus infection, and subsequently, may explain a delayed rhinovirus clearance in low-cd hivinfected patients, resulting in persistent shedding and increased prevalence. we observed a high rate of dual infection, either virusbacteria or virus-opportunistic pathogen. these findings made us consider the prognostic impact of such coinfections. studies in icu adult patients with pneumonia suggested that virus-bacteria coinfection was associated with a worse prognosis [ ] . in mice, the coinfection of influenza with streptococcus pneumoniae [ ] , legionella pneumophila [ ] or staphylococcus aureus [ ] impaired the anti-influenza immune response and increased mortality. whether similar synergistic effects exist in virusopportunistic pathogen coinfection remain unknown. only one animal study has explored the couple pneumocystis jirovecii-influenza, but in a successive rather than concomitant model [ ] . unfortunately, in our study, the low number of observations prevented us from analyzing the prognosis according to the presence of coinfections. our study has several limitations. first, this study included adult patients with arf that required icu admission, preventing any conclusion on other populations such as hiv-infected children or hiv-infected adults with arf that did not require icu admission. second, the study was retrospective, so we did not control the microbiological investigations. the preferred sample for mpcr test in non-intubated patients was not the sputum, but the nasopharyngeal swab [ ] . several factors may have discouraged clinicians to use sputum, including the high number of patients unable to produce sputum [ ] and the highly viscous nature of this sample that can make nucleic acid extraction difficult [ ] . by definition, an mpcr was performed in the respiratory tract of every included patient because it was a criterion for patient screening. but some other microbiological tests were only occasionally performed, i.e., cytomegalovirus pcr. furthermore, the retrospective design prevented us from obtaining a number of data, which were rarely reported in medical records by physicians, including vaccine history, pneumocystis jirovecii prophylaxis, symptoms before hospital referral, and duration of symptoms before icu admission. third, only patients having undergone an mpcr in the respiratory tract within the h following their icu admission were screened; this might suggest a confounding of indication. fourth, the choice to classify patients according to their cd lymphocyte count on the icu admission, instead of the latest known value, might be criticized. however, this choice was guided by the high number of missing values in the latest cd lymphocyte count as well as the number of newly diagnosed patients without any prior cd lymphocyte count. fifth, we assumed that a virus identified with pcr in nasopharyngeal or lower respiratory tract samples was always a pathogen of the respiratory tract, whatever the clinical picture and radiological features. this might be criticized since respiratory viruses might be present in asymptomatic adult subjects [ ] , even if it seems rare, about % of asymptomatic adults seen at the emergency department [ ] . sixth, to avoid overinterpreting the data, we decided to consider respiratory viruses as a homogeneous group of pathogens in the analysis stratified by respiratory virus-associated infection. this might be criticized since the pathogenicity differs from one viral species to another. viruses are frequently identified in the respiratory tract of hiv-infected patients with arf that required icu admission, but with a non-viral copathogen in two-thirds of cases. rhinovirus is the predominant viral specie; its prevalence is highest in patients with a cd lymphocyte count below cells/µl. supplementary information accompanies this paper at https ://doi. org/ . /s - - - . additional file . additional information on material and methods, table s (panels of mpcr kits used in the two participating icus over the -year study period), table s (microbiological investigations performed in hiv-infected patients admitted to the icu for acute respiratory failure, according to the diagnosis of respiratory virus-associated infection), table s (baseline characteristics, behavior during icu stay, and outcome of hiv-infected patients admitted to the icu for acute respiratory failure, according to the diagnosis of respiratory virus-associated infection), table s (multivariate analysis of the risk factors for death at day- in hiv-infected patients admitted to the icu for acute respiratory failure), figure s (distribution of the microbiological documentations in hivinfected patients admitted to the icu for acute respiratory failure), figure s admissions to intensive care unit of hiv-infected patients in the era of highly active antiretroviral therapy: etiology and prognostic factors etiologies and outcome of acute respiratory failure in hivinfected patients temporal trends in critical events complicating hiv infection: - multicentre cohort study in france survival for patients 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international survey of knowledge and practice among intensivists diagnostic value of microscopic examination of gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia comparison of sputum and nasopharyngeal swabs for detection of respiratory viruses publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations none. gv had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. ae participated in the design of the study, participated in the data acquisition, analysis and interpretation, and the statistical analysis, and drafted the manuscript. jp, bv, as, lb, qp, jp and vl participated in the data acquisition, analysis and interpretation, and helped to revise the manuscript. rs participated in the data analysis and interpretation, and the statistical analysis. mf and jft participated in the design of the study, participated in the data analysis and interpretation, and helped to revise the manuscript. gv designed the study, participated in the data analysis and interpretation, and the statistical analysis, and revised the manuscript. all authors read and approved the final manuscript. none. data and materials supporting the findings of this study can be entirely shared if asked. not applicable. the authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. key: cord- -q trgj authors: robert, rené; kentish-barnes, nancy; boyer, alexandre; laurent, alexandra; azoulay, elie; reignier, jean title: ethical dilemmas due to the covid- pandemic date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: q trgj the devastating pandemic that has stricken the worldwide population induced an unprecedented influx of patients in icus, raising ethical concerns not only surrounding triage and withdrawal of life support decisions, but also regarding family visits and quality of end-of-life support. these ingredients are liable to shake up our ethical principles, sharpen our ethical dilemmas, and lead to situations of major caregiver sufferings. proposals have been made to rationalize triage policies in conjunction with ethical justifications. however, whatever the angle of approach, imbalance between utilitarian and individual ethics leads to unsolvable discomforts that caregivers will need to overcome. with this in mind, we aimed to point out some critical ethical choices with which icu caregivers have been confronted during the covid- pandemic and to underline their limits. the formalized strategies integrating the relevant tools of ethical reflection were disseminated without deviating from usual practices, leaving to intensivists the ultimate choice of decision. in their daily practice, intensivists are used to facing to ethical concerns related to admission or non-admission to icu, to withholding or withdrawing life support and to communication with families. the devastating pandemic that has stricken the worldwide population induced an unprecedented influx of severe ards patients dramatically exceeding icu bed capacities in several areas of many countries. as a result, four new options never applied to date were considered with the common aim of saving a maximum number of lives: to prioritize icu beds for patients with the best prognosis; to increase at all costs the number of icu beds, thereby creating stepdown icus; to organize transfer to distant icus with more beds available, or to accelerate withdrawal of life support in icus. additionally, to protect the patients' relatives, visits for families were prohibited or strongly limited and adequate communication between caregivers and families was disrupted, counteracting more than years of research aimed at improving interaction with families and quality of care during eol [ ] . moreover, since most health care facilities were being used for covid- patients, the situation also raised concerns inside the icu for patients without covid- requiring icu admission. in such a crisis, there are ingredients liable to shake up our ethical principles, sharpen our ethical dilemmas, and lead to situations of suffering for caregivers [ ] . faced with these profound changes in patient management, intensivists were caught off guard, forced by the density of work, the lack of immediately available beds and the possibilities of transferring patients to make painfully experienced choices that were contrary to their basic ethical principles and source of immediate burden [ ] [ ] [ ] . the aim of this paper is to focus on and to discuss the main ethical concerns raised during the pandemic, especially with regard to icus. since there are differences between health organizations in different countries around the world, ethical perception may vary according to legal or societal specificities. however, even though our thinking was based on french management of the crisis, similar approaches were assessed in other countries, especially in europe and ethical questioning is commonly shared by intensivists throughout the world. the massive influx of patients raised questions on the eventual modification of our admission criteria to the detriment of the most vulnerable populations. the decision to refuse admission of a severely ill patient to an icu is a regular part of the intensivist's work. guidelines have been drawn up to guarantee fairness, avoid unreasonable obstinacy and ensure respect for the patient's wishes and transparency with families [ ] . theoretically, even during an epidemic icu patient admission decision-making should be identical to that of a routinely applied decision-making method. however, the number of requests for admission made at a time of extreme scarcity of icu beds dramatically increased. it has been shown that in case of shortage of icu beds, the criteria for patient selection are modified, patients being more frequently considered as necessitating mainly palliative comfort care [ , ] . it is also necessary to underline the increased risk of mortality for patients who cannot be admitted to icu due to lack of beds, whatever the secondary course adopted: delayed admission, transfer to another distant unit or admission to a less specialized unit [ ] . faced with a massive influx of patients and extreme scarcity of icu beds, the theoretical risk of "sacrificing the most vulnerable patients" shakes our ethical convictions. herein, a triage plan with ethical justifications (table ) has been proposed to maximize benefit for the greatest number of people [ , , , ] . were the plan to be applied, utilitarian ethics would take precedence over individual ethics and employ the means least restrictive to individual liberty in view of accomplishing the public health goal. in other words, an unprecedentedly dramatic experience has taken place in which, due to compressed temporality, exacerbated emotional factors and massive influx of patients, a choice in the sorting cursor is made to the detriment of a reasoned strategy. such a situation is likely to contradict our caregiving-based ethical values [ ] . indeed, in addition to the elements linked to the lack of available beds, several factors in the decisionmaking process were sources of concern: reduction of the minimum time necessary to make such occasionally "life-or-death" decisions, decrease due to containment measures in the essential time to be spent with relatives and pressure from the continuous flow of arriving icu patients. in parallel with war medicine or disaster situations, prioritization strategies have been proposed [ , ] . although such prioritization is not supposed to be opposed to the ethical issues of icu access, in a specific epidemic situation this approach is nevertheless in conflict with our principles insofar as it allows utilitarian ethics to take precedence over ethics based on personhood. in this strategy, doing the greatest good for the greatest number may be inadequate insofar as it ignores other ethically relevant considerations. among the ethical principles ( table ) , prediction of number of years to live is posited as the priority selection criterion, which means that the youngest individuals should receive priority, thereby applying the life-cycle principle in allocation decisions [ ] . however, this appears to be only the least bad of existing or proposed justifications. decision trees have been proposed and simplified specific criteria have been requested, so to shorten the previously implemented regulatory period; this is in contradiction with a recommended practice, which privileges clinical contact with the patient. a simple score integrating the sofa score and the estimate of a probability of death at or years has been used, leading to the creation of a three-grade priority standard [ , ] . although numerous studies have demonstrated the relevance of such scores on an overall population scale, their lack of sensitivity or specificity at the individual level has been repeatedly underlined [ ] [ ] [ ] . indeed, the crude auroc for sofa score predicting in-hospital mortality is only . , leaving one out every four patients with an inappropriate decision [ ] . similarly, the ability to predict a given patient's life expectancy or risk of mortality at or years is generally poor. when applied, such first come, first served lottery strategies must assume "mistake of prophecy" and the eventual sacrifice of wrongly predicted patients. similarly, age becomes a potentially easy operational cursor, which we do not know how to place rationally [ ] . however, whatever the angle of attack, we can only make our choices using ethically flawed approaches. thus, shared recommendations including an admission decision-making checklist incorporating frailty score, comorbidities and, quality of life evaluation (table ) , have been developed and published on covid-crisis websites [ , ] helping intensivists to make such decisions. to conclude, rather than promoting unrefined and imprecise outcome prediction, a pragmatic multimodal approach taking into account frailty score and, comorbidity indices while leaving room for physician judgment should be considered as the best possible [ ] . as another application of the societal concept, it has been proposed to prioritize for icu care the caregivers who have become critically ill, not due to their intrinsic quality or for so as to "reward" them, but rather for the possibility, once they are cured, of being returning to the operational caregiving circuit [ ] . this raises at least two issues: first, the illusion of a rapid return to the caregiver circuit after resuscitation care for a severe form of the disease [ ] , and second, the choice of target actors for such prioritization. this appears to be an insoluble brain teaser: why not prioritize other societal actors who may favor the fight against pandemic such as researchers or other professionals helping to maintain the balance of our society in times of acute crisis? and with respect to the ethical principle of distributive justice, how is one to say that one life is worth more than another? moreover, utilitarian theories of emergency icu bed allocation have been criticized in the theoretical literature, especially on the ground of inequity in application of criteria that may disadvantage existing vulnerable populations [ ] . one solution to overcome the shortage of icu beds during a pandemic is to quickly set up new icus. this requires available rooms in the hospital or the rapid construction of new units, as has been done in china. this option effectively increased the number of icu beds by almost % in several countries and facilitated on-the-spot admission of large number of patients requiring mechanical ventilation. it was rendered possible by the dedication of volunteer health care workers (hcws) having agreed to work in a new and singularly stressful environment. however, this option has been associated with a significant risk of reduced quality of care for several reasons associated with the difficulties in meeting nationwide standards for critical care facilities in this type of emergency context. first, rooms converted from intermediate care units or post-operative recovery rooms are not adequately designed for the all the equipment and organization required in critical care. second, volunteer hcws recruited to work in icus may not adequately be trained for specific and sophisticated icu work despite the hastily improvised teaching sessions or "crash courses" organized to help them learn. along with the risk of decreased skill level, insufficient training of these hcws increases the burden of work [ ] . third, in the context of a pandemic, highly sophisticated devices, especially ventilators, are frequently lacking. this leads to use of inappropriate devices for the complex care of severe ards patients. to sum up, while the possibility of quickly setting up "neo-icus" permits admission of a large number of very severe critically ill patients, it also entail a possible risk of downgraded quality level of care and subsequent impaired prognosis, as shown in other situations [ , ] . additionally, this type of organization may imply distributive inequality, with access to icu facilities of heterogeneous efficiency and with a selection criterion recording in the patient's medical file that would be close to first come-first served, which could become first come-best served. epidemic intensity and icu bed availability were reported to vary strongly across countries and also within regions in a single country. to mitigate these "geographic" inequalities, patient transfers from regions with dramatic shortages of icu beds to areas less affected by the outbreak and with a large amount of available icu beds along with including optimal material and icu staff, have been implemented. these transfers require aircrafts, helicopters or trains that have been sophistically adapted to the care of critically ill patients and necessitate the involvement of a large number of dedicated physicians and nurses to ensure adequate organization and optimal patient safety. notwithstanding its complexity, in order to be efficient this transfer strategy should be organized within a short period of time and should allow the transfer of a significant number of patients. it is associated with increased costs that should not be charged to the patient or his or her relatives. the first ethical issue surrounding such transfers is related to the benefit/risk balance. for the patient, the benefit of being in the hands of highly qualified teams is counterbalanced by the risk of clinical worsening during transfer. during patient selection, close attention should be paid to severity status: not too severe (transfer would be too risky), and not too well (to avoid unnecessary transfer). while informed patient consent should theoretically be part of the decision, most of the transferred patients were unconscious and unable to approve such a transfer, thereby ruling out the autonomy principle. informed consent was consequently obtained from their next of kin (patients whose next of kin refused were not transferred). a second ethical issue concerns the icu departments accepting patients from a distant region and possibly aggravating the risk of a suddenly increased epidemic wave in their own area. indeed, covid pandemic experience has shown that we did not have efficient predictive tools to precisely anticipate the kinetics of icu bed requirements. finally, such transfers may be associated with increased suffering and psychological trauma for the relatives. indeed, long distance and limitation of travels for epidemic control will strongly impede if not altogether rule out the presence of relatives at the patient's bedside and prevent adequate communication between them. this could exacerbate pain for the families, especially if specific communications are not developed (see below). it has been proposed to relieve the icu teams in charge of patient care of the responsibility of admission or nonadmission decisions and to entrust this work to a dedicated triage team headed by a triage officer [ , ] . the advantage of this approach is that it relieves the healthcare team of the emotional impact of a potentially painful ethical dilemma [ ] . however, the composition of these triage teams must be specified. mentions of volunteers, leaders recognized by their peers and by the medical community have been put forward [ ] . it should no doubt be specified that the triage leaders will be intensivists recognized for their ethical sensitivity, and an overly "military" strategy should be scrupulously avoided [ ] . if not, the potentially protective role of independent triage teams can be a source of additional injury for caregivers, disappointed with their patient's unfavorable outcome and even blamed for an unshared therapeutic cessation decision or dehumanization of care [ ] . it has been suggested that patient severity assessments be intensified during their progress in icu stay, so that the withdrawal of one patient's mechanical ventilation can benefit another patient [ ] . in this way, withdrawal of artificial ventilation might be decided when the improvement is not fast enough, while hopes of survival may persist. similarly to the triage team, it has been proposed to use triage committee to buffer clinician from potential harm [ , ] . again, the risk of ethical drift must be emphasized. despite an influx of patients and lack of beds, it does not seem ethically acceptable to lose a chance for patients for whom treatment does not seem to be unreasonable obstinacy. moreover, the appreciable time taken to make these decisions is an element that risks being called into question during an epidemic emergency. finally, under the pretext of risk of contamination and need for confinement, exchanges with relatives to share final decisions could be reduced if not eliminated, a factor entering once again into contradiction with basic ethical concepts. it must be admitted that in a crisis situation with an unprecedented influx of patients in icu, no single strategy fully corresponds to our ethical values. whatever the approach adopted, imbalance between societal and individual ethics leads to unsolvable discomforts that caregivers will have to overcome. in other words intensivists would have to consider their own tension between utilitarianism (making icu beds available rapidly, potentially sacrificing patients without rapid improvement for new admissions) and virtue (accept to prolong icu stay for an icu patient even if there is no bed available to admit another patient) ethics. fortunately, the formalized strategies of ethical reflection associated with decision-making for withdrawal of life support therapies have long since been part and parcel of routine practice, leaving the ultimate choice of decision up to the intensivist. the heterogeneity in eol-decision-making is probably huge across hospitals and icu. postponed decision-making or even paralysis at eol may have created excess in mortality due to shortage of icu beds. nevertheless, confidence should be given to icu teams to manage the eventual withdrawal of life support decision through a bedside decision-making process taking into account the exceptional difficulties linked to the epidemic situation. since discrepancies may exist between experts' ethical recommendations and public perception, general public opinion has been investigated based on the basis of deliberative democracy [ , ] . a -participant panel placed in a simulated context of a severe influenza pandemic favored ethical principles of saving the most lives (surviving current illness) and saving the most life-years (living longer) over a first come first serve scenario [ ] . however, a significant number of participants were opposed to the idea of ventilator reallocation [ ] . in this study, subgroup differences associated with age or ethnicity of the participants were pointed out [ ] . in another survey, the pragmatic constraints imposed by an assumption of extreme scarcity were not accepted by the canadian participants, who expressed difficulties in making priority-setting decisions because these were perceived as psychologically burdensome, no-win situations [ ] . transparent communication is also important during such a crisis so as to allow public opinion to be able to better understand place the decisions of icu teams. the covid- epidemic is a threat to family-centered care in icus. during the st weeks of the epidemic, visits were prohibited to ensure that relatives did not contaminate other family members, patients, or healthcare professionals. family members could no longer be at the patient's bedside and the icu team was unable to propose structured communication and support to family members. involvement in decision-making was compromised, and it was felt that this situation was harmful both for patients and family members. indeed, over the last decade, research has shown that post-icu syndrome (pics-f) [ ] in family members is a cause of major concern. the major risk factors for pics-f are poor communication with an icu team, being in a decision-making role, low educational level, and having a loved one who died or was close to death. indeed, many studies have shown that communication with caregivers is one of the most highly valued aspects of care and that impacts-on family members' experience during and after the patient's stay, including in the aftermath of the patient's death [ , ] . communication perceived as inconsistent, unsatisfactory or uncomforting is associated with higher risk of post-icu burden [ ] . risk of ptsd-related symptoms increases when relatives, both non-bereaved and bereaved, feel that the information given is incomplete [ ] . after death in the icu, bereaved family members are at high risk of presenting symptoms that negatively affect their quality of life, such as anxiety, depression, ptsd symptoms [ , ] and complicated grief [ ] . interestingly, family members who witness a relative of theirs suffering from dyspnea are at higher risk of developing ptsd-related symptoms and those who are not able to say goodbye to relative of theirs are at higher risk of developing complicated grief symptoms [ ] . in the context of the covid- pandemic, risk factors for developing post-icu burden are numerous, thereby increasing exposure to anxiety, depression, ptsd and complicated grief. as said in the new york times, "of all the ways the coronavirus pandemic has undermined the conventions of normal life, perhaps none is as cruel as the separation of seriously ill patients and their loved ones, now mandated at hospitals around the world" [ ] . faced with these various difficulties and risks, recommendations have been published regarding communication with family members in this specific context. first, patients and family members should receive clear explanations, both directly (over the phone or when present) and on institutional websites, concerning the imposed restrictive policies: it is important that they understand why they cannot visit their loved one [ ] . in other words, the restriction must have meaning. second, icu teams are encouraged to proactively schedule routine telephone calls with family members to maintain continuity of communication [ ] . the calls must follow a plan so that family members know when to expect contact. the phone calls will not only address the patient's health status, but also provide reassurance regarding comfort and dignity [ ] . conversations are important to help the icu team better understand the patient as a person (values, advance directives, etc.) and to help family members think about possible difficult decisions. in this context, goal-concordant care is particularly important and icu teams must strive to avoid intensive life-sustaining treatments that would be unwanted by patients [ ] . on a parallel track, strategies to reinforce communication between the patient and the family have been developed. icu teams should encourage patient and family to call, text, and videoconference with each other as often as wanted [ ] . they may also help the patient and family members record and send audios, videos, or written messages to one another. if the patient is unconscious, the icu team can print written messages or family photos and stick them in a diary that can then be given to the patient. staying in touch is vital, both for the patient and for the family members. moreover, many icu teams have made visitation policies more flexible. these units have adapted themselves to the influx of patients while respecting a predetermined protocol. the visitor must have a dedicated time appointment and wait in a room where he/she may not meet other visitors. instructions on hygiene are given by the nurses. psychological support for each visit and followup calls by the icu psychologist are also recommended. visiting a loved one in intensive care is very upsetting in the best of times, but when in addition one has been separated for days, perhaps weeks, there is also all the emotional pressure of a long-awaited reunion. in end-of-life (eol) situations, the icu team must avoid depriving family members of the opportunity to say goodbye to the patient [ ] . if visitation is usually forbidden in the icu, it should be made possible in an eol situation. if the family cannot or does not want to come to the icu, letting him/her speak to the patient one last time over the phone is important. family members need to prepare for bereavement, meaning they must understand what is happening: end-of-life family conferences should be organized, remotely if needed [ ] . honest conversations are important, as helping family members prepare for death is an important part of anticipatory grief [ ] . not being prepared is associated with increased risk of complicated grief. when possible, respecting the family's wishes is particularly important in a context where the grief process may be more complex as families are unable to see their loved one's body, to physically share their emotions with other relatives and, sometimes even to attend their loved one's burial. in the current pandemic, sources of psychological disorders for hcws are multiple. they are affected by distress similar to than the general population regarding the effects of lockdown and containment, the risk of personal or families' and friends' illnesses, the uncertainty about pandemic duration and, the lack of effective specific treatment. this dearth of knowledge has given rise to a great deal of contradictory information that has forced health care professionals to constantly readapt and to cope with the experience of powerlessness and personal ineffectiveness [ , ] , and they also experience "front line" specific factors [ ] . the factors include extended workloads, feelings of powerlessness when trying to contain the large number of patients, concerns about the suffering and potential poor outcomes of their patients, preoccupations about potential shortages of intensive care resources (including personal protective equipment), the fear of transmitting the disease to their loved ones, and apprehension about possible involvement in ethically difficult resource allocation decision-making. this situation has created a high level of uncertainty and insecurity that constitutes a risk to the mental health of caregivers [ , ] . to date a few studies have reported a quantification of symptoms amongst hcws. all of them have shown an increase in psychological disorders compared with different control groups providing no direct care to patients: [ , [ ] [ ] [ ] ] . fear was more frequent than anxiety and depression with incidences varying from , , % to , , %, respectively [ , ] . assessments by other scales confirmed two-thirds of mental health disorders, especially in young women [ ] . sleep disorders were also reported [ ] . in some countries, e.g., in italy or in france, healthcare workers are applauded by the population each evening at pm. societal reward and "glorification" [ ] of the caring function appears to be a protective factor in the short term [ ] and in his first address to the nation, the president of france, emmanuel macron, called healthcare workers "the heroes with a white coat". it may be dangerous for healthcare workers to fall into this trap. altruism has long since been recognized as a core value of this profession. moreover, a hero must keep silence about his feelings, a factor which is known to favor burnout [ ] . insecurity and uncertainty are reflected not only at an individual level, but also at a collective level. the covid- epidemic requires reinforcement of the icu teams with new staff members or even reorganization of the unit, weakening the reference points and trust within the team. this context creates a feeling of vulnerability and loss of control for professionals [ , ] . a lack of interaction between caregivers and families induces a feeling of exclusion and even a significant emotional burden when patients die, highlighted in certain cases by a feeling of guilt [ ] . psychological support has been set up for caregivers, as many hospitals have initiated telephone hotlines, psychologists within units, relaxation sessions, meditation, discussion groups, and optimization techniques. these responses should ideally vary according to the phase of the pandemic [ ] . at the early phase, the best way to prevent psychological disorders is to acknowledge staffers' work by providing adequate human resources and material supplies [ ] . both frequency and transparency in hospital communication likewise play a key role [ , ] . concrete measures to set up rest areas, to facilitate the logistics of meals, daily life, and the possibility of having leisure and relaxation time are optimally appropriate to the needs of the caregivers during the crisis. at this stage, this type of collective support could be more effective than individual support. however, individual assessment of mental health may later become relevant. in a study in wuhan, the most valued psychological resources consisted in social media ( %) and psychological guidance books ( %) [ ] . requests for therapist-driven video calls or consultations were less frequent ( %) and rose the question of their availability, given the large number of affected hcws [ ] . similarly, a form of reluctancy, or even an absence of solicitation of the listening units in times of health crisis has been reported [ , ] . to overcome the covid- pandemic, in many places throughout the world, new resources were developed in a short period of time, dramatically increasing the number of icu beds allowing admission of a huge number of critically ill patients. the massive patient influx highlighted numerous ethical concerns that icu caregivers are likely to face. some models have proposed ethical justifications to difficult decision-making, usually based on deontological (or societal) rather than individual ethics. we wished to draw attention to the risk of taking refuge behind ethical alibis notwithstanding the fact that the specific pandemic context there is no single satisfactory solution. in such a situation each option is associated with its own strengths and weaknesses, and intensivists should make their choices in full awareness of intractable ethical dilemmas. in many circumstances, caregivers have no choice but to adopt less than perfect solutions even though the price to be paid consists in undermining patients' , relatives' and caregivers' psychological wellbeing. lessons should be learnt from this experience and ethical reflections should be developed in order to anticipate a potential new pandemic in the close or more distant future. abbreviations eol: end-of-life; hcws: healthcare workers; icu: intensive care unit. guidelines for family-centered care in the neonatal, pediatric, and adult icu a coronavirus cautionary tale from italy: don't do what we did a framework for rationing ventilators and critical care beds during the covid- pandemic triage of scarce critical care resources in covid- an implementation guide for regional allocation factors associated with mental health outcomes among health care workers exposed to coronavirus disease recommendations for end-of-life care in the intensive care unit: a consensus statement by the american college [corrected] of critical care medicine intensive care unit bed availability and outcomes for hospitalized patients with sudden clinical deterioration influence of icu-bed availability on icu admission decisions refusal of intensive care unit admission due to a full unit: impact on mortality surge capacity logistics: care of the critically ill and injured during pandemics and disasters: chest consensus statement fair allocation of scarce medical resources in the time of covid- allocating medical resources in the time of covid- scarce resource allocation during disasters priorisation des traitements de réanimation pour les patients en état critique en situation d'épidémie de covid- avec capacités limitées. société française d' anesthésie réanimation, service de santé des armées too many patients…a framework to guide statewide allocation of scarce mechanical ventilation during disasters understanding articles describing clinical prediction tools. evidence based medicine in critical care group predicting death and readmission after intensive care discharge the proliferation of reports on clinical scoring systems: issues about uptake and clinical utility prognostic accuracy of the sofa score, sirs criteria, and qsofa score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit effect of systematic intensive care unit triage on long-term mortality among critically ill elderly patients in france: a randomized clinical trial décision d'admission des patients en unités de réanimation et unités de soins critiques dans un contexte d'épidémie à covid- clinical ethics recommendations for the allocations of intensive care treatments, in exceptional, resource-limited circumstances long-term outcome after the acute respiratory distress syndrome: different from general critical illness? priority setting of icu resources in an influenza pandemic: a qualitative study of the canadian public's perspectives prepared to respond? exploring personal disaster preparedness and nursing staff response to disasters physician staffing patterns and clinical outcomes in critically ill patients: a systematic review esicm working group on quality improvement, valentin a, ferdinande p. recommendations on basic requirements for intensive care units: structural and organizational aspects the toughest triage-allocating ventilators in a pandemic ventilator triage policies during the covid- pandemic at u.s. hospitals associated with members of the association of bioethics program directors emotional impact of end-of-life decisions on professional relationships in the icu: an obstacle to collegiality? post-intensive care syndrome: an overview in their own words: patients and families define high-quality palliative care in the intensive care unit improving comfort and communication in the icu: a practical new tool for palliative care performance measurement and feedback. qual saf health care family response to critical illness: postintensive care syndrome-family risk of post-traumatic stress symptoms in family members of intensive care unit patients predictors of symptoms of posttraumatic stress and depression in family members after patient death in the icu complicated grief after death of a relative in the intensive care unit family-centered care during the covid- era a -point strategy for improved connection with relatives of critically ill patients with covid- covid-ready communication skills: a playbook of vitaltalk tips the importance of addressing advance care planning and decisions about do-not-resuscitate orders during novel coronavirus (covid- ) not dying alonemodern compassionate care in the covid- pandemic grief during the covid- pandemic: considerations for palliative care providers les professionnels de santé face à la pandémie de la maladie à coronavirus (covid- ): quels risques pour leur santé mentale? l'encéphale a study on the psychological needs of nurses caring for patients with coronavirus disease from the perspective of the existence, relatedness, and growth theory clinician wellness during the covid- pandemic: extraordinary times and unusual challenges for the allergist/immunologist mental health care for medical staff in china during the covid- outbreak psychological impact of the covid- pandemic on health care workers in singapore psychological status of medical workforce during the covid- pandemic: a cross-sectional study online mental health services in china during the covid- outbreak impact on mental health and perceptions of psychological care among medical and nursing staff in wuhan during the novel coronavirus disease outbreak: a crosssectional study social capital and sleep quality in individuals who self-isolated for days during the coronavirus disease (covid- ) outbreak in january in china on behalf of the entire editorial and publishing staff of jama and the jama network. health care heroes of the covid- pandemic an official critical care societies collaborative statement-burnout syndrome in critical care health-care professionals hospital preparedness and sars immediate and sustained psychological impact of an emerging infectious disease outbreak on health care workers timely mental health care for the novel coronavirus outbreak is urgently needed annals for hospitalists inpatient notes-preparing for battle: how hospitalists can manage the stress of covid- protecting healthcare workers during the coronavirus disease (covid- ) outbreak: lessons from taiwan's severe acute respiratory syndrome response publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors wish to thank jeffrey arsham for reviewing and editing the original english-language manuscript. authors' contributions rr: conception and design of the work. rr, nkb, ab, al, jr, ea: drafted the manuscript and revised it. all authors read and approved the final manuscript. not applicable. not applicable. not applicable. not applicable. the authors declare they have no conflict of interest. key: cord- -zwh xj u authors: al-dorzi, hasan m.; aldawood, abdulaziz s.; khan, raymond; baharoon, salim; alchin, john d.; matroud, amal a.; al johany, sameera m.; balkhy, hanan h.; arabi, yaseen m. title: the critical care response to a hospital outbreak of middle east respiratory syndrome coronavirus (mers-cov) infection: an observational study date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: zwh xj u background: middle east respiratory syndrome coronavirus (mers-cov) has caused several hospital outbreaks, including a major outbreak at king abdulaziz medical city, a -bed tertiary-care hospital in riyadh, saudi arabia (august–september ). to learn from our experience, we described the critical care response to the outbreak. methods: this observational study was conducted at the intensive care department which covered icus with single-bedded rooms. we described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. the clinical course and outcomes of healthcare workers (hcws) who had mers were noted. results: sixty-three mers patients were admitted to mers-designated icus during the outbreak (peak census = patients on august , , and the last new case on september , ). most patients had multiorgan failure. eight hcws had mers requiring icu admission (median stay = days): seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. the hospital mortality of icu mers patients was . % ( % for the hcws). in response to the outbreak, the number of negative-pressure rooms was increased from to rooms in mers-designated icus. patients were managed with a nurse-to-patient ratio of : . . infection prevention practices were intensified. as a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~ % and n masks were used per patient/day on average. family visits were restricted to h/day. although most icu staff expressed concerns about acquiring mers, all reported to work normally. during the outbreak, . % of nurses and . % of physicians working in the mers-designated icus reported upper respiratory symptoms, and were tested for mers-cov. only / ( . %) icu nurses and / ( . %) physician tested positive, had mild disease and recovered fully. the total sick leave duration was days for nurses and days for physicians. conclusions: our hospital outbreak of mers resulted in patients requiring organ support and prolonged icu stay with a high mortality rate. the icu response required careful facility and staff management and proper infection control and prevention practices. the middle east respiratory syndrome (mers) coronavirus is a recently identified virus that is closely related to the severe acute respiratory syndrome coronavirus (sars-cov) [ ] , causes severe hypoxemic respiratory failure with multiorgan failure and frequently requires admission to the intensive care unit (icu) [ , ] . as of september , , the world health organization (who) reported laboratory-confirmed cases, including related deaths [ ] . the majority (~ %) of mers cases occurred in saudi arabia [ ] , where several hospital outbreaks happened [ , ] with % of all cases taking place within healthcare facilities [ ] . the outbreak in the republic of korea illustrated the global threat of this disease. it started in may and resulted from a case with travel history to the arabian peninsula [ ] . human-to-human transmission occurred to close contacts [family members, other patients and healthcare workers (hcws)] and led to cases of mers-cov infections with % fatality rate. in our hospital, king abdulaziz medical city-riyadh, an outbreak of mers disease occurred in august to september [ ] , led to significant disruption of hospital functions and resulted in mers cases [ ] with patients requiring icu admission. the outbreak was attributed to crowding, movement of infected but undiagnosed patients and breaches in infection prevention and control practices [ ] . details of the hospital outbreak have been published elsewhere [ ] . most of the medical literature on mers has focused on describing the characteristics and outcomes of affected patients. preparedness and the response of the healthcare system at its different levels are crucial to contain this disease and manage its associated outbreaks. nevertheless, little is published about how the healthcare system responded to the disease and hospital outbreaks. the objective of this study was to describe the response of the icu to a hospital mers outbreak, the associated changes in its workflow and the impact on its hcws. this study was an observational study conducted at the intensive care department of king abdulaziz medical city, a -bed tertiary-care referral hospital in riyadh, saudi arabia, that was accredited by the joint commission international. the hospital had an infection prevention and control department. the intensive care department covered units: an -bed trauma icu (unit a), a -bed medical-surgical intensive care unit (unit b), a -bed surgical icu (unit c), an -bed neurologic icu (unit d) and a -bed stepdown unit (unit e). the department also provided coverage to boarding patients in the -bed resuscitation area in the emergency department (ed). the hospital had also an -bed burn icu. the icus were operated as closed units with -h, -day onsite coverage by boardcertified critical care intensivists [ ] . normally, medical teams covered the units during the day with each team consisting of one intensivist consultant, one registrar/ fellow and - residents. the nurse-to-patient ratio in all the icus was mostly : . one certified respiratory therapist covered a maximum of six ventilated patients. additionally, the department had a rapid response team, which covered the hospital wards and was activated according to predefined criteria and is covered by a sixth separate team [ ] . the department has had several ongoing quality improvement projects and indicators. infection prevention and control practices, such as hand hygiene and the ventilator care bundle, were monitored by multidisciplinary icu teams and the infection prevention and control department [ ] . for intubated patients, ventilator care was provided by specialized respiratory therapists and included using closed endotracheal suctioning systems which were changed every h or as clinically indicated [ ] , changing the ventilator circuits in between patients or if they became soiled or damaged [ ] , and using heat and moisture exchangers which were changed every days or when visibly soiled [ ] . due to the high prevalence of multidrug-resistant organisms and prior cases of influenza and mers infection in the hospital, droplet precautions were applied to all icu patients since february [ ] . sporadic cases of mers cases have been managed in our icu since february . the characteristics, management and outcomes of the initial mers cases managed in our unit were described previously [ ] . all hcws were required to undergo fit testing for the n respirators (table ). an infectious disease epidemic plan (idep) was initially released in may and was revised in march . table describes selected plan elements. according to the idep, one unit (unit a) was designated as the primary receiving unit for mers patients, because of its geographic location being away from main hospital traffic and because of its rooms were negative-pressure airborne infection isolation rooms (aiir). the plan was not explicit about which units would be used if the number of cases exceeded the capacity of this unit. however, unit b had negative-pressure rooms. in our hospital, mers was suspected based on clinical presentation and confirmed by laboratory testing as recommended by the who and the saudi ministry of health [ , ] . in our icu, the workup of patients having lower respiratory tract infections was standardized to include bacterial gram stain and culture, mers-cov polymerase chain reaction (pcr), h n pcr, bacterial and viral multiplex pcr on respiratory samples, mycoplasma, chlamydia and legionella serology and, if suspected, tuberculosis workup. the respiratory samples were routinely obtained by blind deep tracheal aspirate in intubated patients. in the hospital biosafety level laboratory, mers-cov screening was performed by real-time reverse-transcription (rrt) pcr on respiratory samples by checking for the upstream e protein genome (roche modular dx coronavirus) and infection confirmation by detecting the open reading frame a genome (mers-cov kit from tib molbiol) [ ] . laboratory workers were fit-tested and applied n respirators while handing respiratory samples. positive samples were sent to the saudi ministry of health reference laboratory for confirmation. viral culture was not performed as biosafety level is needed. we noted mers cases admitted to the icu from july to october , , and collected data on the clinical characteristics, management and outcomes of the affected hcws. we also obtained data about the rrt-pcr performed for icu patients. we identified the physicians and nurses who reported sick leave for respiratory illnesses. as surrogate for infection control practices, we obtained data on the related consumables for units a and b before and during the outbreak (april- september , ) . we also collected qualitatively our own observations and those of other hcws on the icu response during the outbreak using interviews and open discussions. descriptive data were presented as means and standard deviations or frequencies and percentages, as appropriate. the infection prevention and control consumables were compared in the months before (april to july) and the months during (august and september) the outbreak. the plan will be activated by the chair of the outbreak response committee based on the phase definition phase i - cases of suspected or confirmed in the hospital phase ii - cases of suspected or confirmed in the hospital phase iii > cases of suspected or confirmed in the hospital phase i confirmed mers-cov cases requiring intubation will be assigned a negative-pressure room and cohorted in one icu confirmed cases that have been diagnosed with mers-cov in any icu other than the trauma icu (unit a), shall be transferred to the trauma icu (unit a) as soon as possible. phase ii all mers-cov patients will be cohorted in one unit. if the number of patients exceeds its capacity, then other units are identified to receive the additional cases closure of all nonessential hospital functions phase i all services run without interruptions except for certain precautions for mers patients phase ii all elective surgery shall be canceled to free more icu beds phase iii all elective cardiac surgery shall be canceled outpatient clinic visits shall be limited to urgent visits only healthcare worker (hcw) management all hcws shall be aware of . relevant infection prevention and control policies and procedures . their annual influenza immunization status. if not vaccinated, please contact the employee health clinic to arrange for an appointment . their n fit check/test status. if have not been fit-tested, please contact the employee health clinic to arrange for an appointment hcws exposed to a confirmed mers-cov case shall be assessed according to a predetermined protocol hcws requiring isolation at home and happen to share a room with another hcw will be provided a room in the designated accommodation for isolation till cleared by the infection prevention and control department an infection prevention and control officer is available h per day, days per week in july , five cases of acute respiratory failure were referred to the icu team from the ed and wards and were diagnosed to have mers pneumonia. as the number of mers patients increased, the idep was activated on august , and included strict implementation of infection control measures, including airborne and contact isolation for confirmed and probable mers cases, and droplet and contact isolation for suspected cases [ ] . on august , phase iii of the idep was activated (table ) , which included ed closure, elective surgical procedure cancelation and outpatient clinic suspension [ ] . meanwhile, the icu maintained full operations. figure suspected mers cases had rrt-pcr on nasopharyngeal swabs in nonintubated patients and on deep tracheal aspirates in intubated patients. fiberoptic bronchoscopy was not performed for the diagnostic workup of mers or ventilator-associated pneumonia. repeated testing was frequently needed to make the diagnosis. among our critically ill mers patients, the initial mers-cov testing was performed on nasopharyngeal swabs in and deep tracheal aspirates in the rest (n = ). in the first sample, mers-cov was detected in only / ( . %) nasopharyngeal samples and / ( . %) deep tracheal aspirates. after initial negative or equivocal nasopharyngeal swabs (n = ), a second nasopharyngeal swab was performed in patients (positive in . %) and deep tracheal aspirate in (positive in %). our microbiology laboratory extended its working hours and prioritized testing samples coming from the icu and the rest of the hospital. the number of mers-cov tests performed on icu patients went up from an average of . before to . per day during the outbreak with a maximum of tests on september , . in patients with suspected mers and negative rrt-pcr, the test was repeated after - days. there was a general consensus among our intensivists that three negative lower respiratory samples and low clinical pretest probability were needed to exclude mers-cov infection. for patients with confirmed mers, the test was repeated twice weekly until consecutive tests were negative. the mean age of the patients was . ± . years with the majority ( . %) being males. eight hospital workers required icu admission after acquiring mers. table summarizes their characteristics. half of them did not have direct contact with patients. one of them was a pregnant nurse that worked in the ed. all but one required intubation. the medical management of mers patients was largely supportive. most ( . %) mers patients required endotracheal intubation, which was performed by the most experienced available physician with airborne precautions. lung-protective ventilation was implemented for acute respiratory distress syndrome with tidal volumes ( - ml/kg of ideal body weight). to reduce the airborne generating procedures, we discouraged the use of noninvasive ventilation for suspected mers cases. nevertheless, it was used in the initial management of ( . %) patients. these patients were either suspected to have concomitant cardiogenic pulmonary edema or had milder disease. intubation was needed for patients. highflow oxygen therapy was not used as it was unavailable. when needed, bronchodilators were used via metered dose inhalers rather than nebulizers. most ( . %) mers patients required vasopressors. renal replacement therapy was provided for ( . %) patients. for the hospital workers acquiring mers (n = ), cisatracurium infusion was used in ( . %), early prone positioning in ( %), continuous renal replacement therapy in ( %) and extracorporeal membrane oxygenation in ( table ) . none of the patients received ribavirin, interferon therapy or high-dose steroids. the hospital mortality of mers patients was . % with all deaths occurring in the icu. all hospital workers who had mers survived and were discharged to home. the icu and hospital length of stay were prolonged ( . ± . and . ± . days, respectively). during the outbreak, our hospital established a command center, which met twice daily, and oversaw all interventions in accordance to the idep. the intensive care department chairman was a member of the command center and presented daily the number of suspected and confirmed cases in the icu, bed and staff management issues and any challenges. the department chairman attended all morning handover meetings in the icu where he received input from the icu teams and provided feedback from the command center. the hospital provided an intranet page that had educational material on mers, mers management guidelines and proper infection control practices. the page was regularly updated. additionally, the hospital frequently informed staff about the mers outbreak status through emails. staff could communicate with the command center regarding any outbreak-related concern or question. the intensive care department communicated with the medical staff about the saudi ministry of health and who practice guidelines. before and during the outbreak, the who interim guidance for the management of suspected and confirmed mers-cov infection [ ] was circulated to our icu staff. moreover, a letter expressing gratitude and encouragement was sent from the department chairman to all hcws. family visiting to mers patients was restricted from an open visiting policy to h per day during the evening with visitors not allowed to enter patient rooms. visiting outside these hours was allowed in selected cases if the clinical condition required. to update the patients' families, the icu consultant contacted and updated the next of kin by phone every day and addressed the family concerns. a nurse was assigned to screen all staff and visitors entering each unit by asking for symptoms of acute respiratory infection and measuring temperature. staff and family members with symptoms of acute respiratory illness or fever were not allowed to enter. the initial mers cases were admitted to the designated mers unit (unit a). as the number of patients increased, the icu leadership identified other icus as potential placement units. the hospital clinical engineers converted a total of standard rooms in unit b and unit c to negative-pressure rooms by increasing air exhaust more than supply by cubic feet per minute. as the number of suspected and confirmed mers patients increased, unit b and then unit c were used. as the number of our mers patients increased beyond unit a capacity, patients without mers were transferred to other units or hospitals to increase bed capacity. the old pediatric icu, which was recently vacated in june after the opening of a new pediatric hospital, was used to care for stable and long-term patients. during the outbreak, and patients from units a and b, respectively, were transferred to the other icus (units c-e and the old pediatric icu), and patient to another hospital. the care for mers patients was demanding. for example, of the affected hcws required prone positioning for the management of acute respiratory distress syndrome ( table ). also of them required continuous table ) . the care was also associated with significant exposure risk. this can be reflected in the duration of mechanical ventilation for the hcws who required intubation ( - days) and length of icu stay ( - days) ( table ) . during the outbreak, the nurse-to-patient ratio was mostly : except for one patient on ecmo ( : ). additionally, - additional nurses were deployed in each unit to assist in procedures such as prone positioning and to monitor and correct infection control practices. in unit a, for instance, the nurse-to-patient ratio was : . before the outbreak and became : . during the outbreak. we restricted medical management to the attending physicians, senior registrars and critical care fellows. rotating residents were not allowed to work in the icu during the outbreak. entry of nonclinical staff, such as research coordinators, was restricted and the ongoing clinical trials were put on hold, except for mers studies, to reduce staff exposure. during the outbreak, concerns among icu staff were raised about acquiring mers and transmitting the virus to their families; a concern that was substantiated by seeing hospital workers infected and developing critical illness. however, many felt privileged to be part icu team managing the outbreak and taking care of mers patients; none refused to report to work as per schedule. two pregnant icu nurses were redeployed to low-risk units. staff members who developed fever, respiratory symptoms or gastrointestinal illness were asked not to present to work, but rather to report to the ed or the employee health clinic depending on their illness severity. of the bedside nurses covering units a and b, ( . %) nurses had symptoms of acute respiratory infection during the outbreak and consequently had nasopharyngeal swabs obtained for mers-cov; all tested negative. their total sick leave duration was days (range: - days per nurse). in comparison, in the months before the outbreak, ( . %) nurses had sick leaves for a total of days (range - days per nurse). of the nonresident icu physicians, ( . %) physicians received sick leave for a total of days (range - days per physician). in unit c, two nurses ( . %) of nurses who worked in mers units (units a, b and c) and one rotating resident ( . %) out of physicians covering the icus tested positive for mers-cov. the resident and one of the nurses were symptomatic and required hospitalization in a mers ward for approximately week and both recovered fully. in february , long before the mers outbreak, droplet precautions had been added to the standard precautions for all icu patients, mainly to prevent the transmission of influenza. during the outbreak, airborne precautions were added for all confirmed and suspected mers cases. although all staff were required to be fit-tested for the n respirators before the outbreak (table ) , we discovered that many icu staff were not tested. during the outbreak, a clinic was emergently opened to fit test hcws and the results were documented. specific policies and procedures were developed or updated for donning and doffing personal protective equipment (ppe). related visual instructions were provided inside each icu room. outside patient rooms, carts containing ppe were organized to facilitate donning in the correct sequence. during the outbreak, additional training on hand hygiene techniques and ppe application was provided. housekeepers were also retrained on proper cleaning techniques and ppe use. the intensive care department worked closely with the infection prevention and control department on all aspects of infection control. the implementation of such infection control measures required having adequate ppe supplies, such as respirators, goggles, face shields and gowns. table describes the consumption of surface disinfectants, antiseptic alcohol for hand hygiene, n masks and other ppe before and during the mers-cov outbreak. during the outbreak, the consumption of detergent surface disinfectant and ethyl alcohol for alcohol-based hand rub increased by almost % and the use of n masks increased by > times compared to the preceding months. the number of examination gowns per patient per day decreased during the outbreak probably due to staff avoiding unnecessary exposure. twenty-four powered air-purifying respirators were made available to staff who failed the n respirator fit test. they were used by physicians, nurses and respiratory therapists. training sessions on their application were conducted. in this report, we described how the icu responded to a mers-cov outbreak at a tertiary-care hospital. the outbreak led to mers patients requiring prolonged icu care and most received invasive mechanical ventilation, vasopressors and renal replacement therapy. the overall mortality was %, but all affected hospital workers survived. the outbreak management included almost tripling the icu capacity of negative-pressure rooms and intensifying infection prevention and control practices. even though icu staff had significant exposure risk, very small number acquired mers-cov. response to incidents such as an infectious hospital outbreak requires a robust hospital-wide command and control structure that is able to make rapid informed decisions across an institution. as it was the case in our hospital, the control of outbreak may require major interventions such as closing the ed, suspending elective surgeries, preventing inter-facility patient transfers, canceling ambulatory clinics and outpatient diagnostic procedures, preventing hospital staff from working at other institutions and restricting hospital visitors [ ] . our hospital had a preexisting idep, which facilitated managing and containing the mers-cov outbreak. such a plan is mandatory for every hospital. mers infection is associated with several challenges. its presenting symptoms overlap with those of other severe acute respiratory illnesses and include fever ( %), cough ( %), dyspnea ( %) and diarrhea ( %) [ ] , often in older adults with preexisting chronic comorbidities [ , ] . common laboratory abnormalities include leukopenia, lymphocytopenia, thrombocytopenia and elevated serum creatinine, lactate dehydrogenase, and liver enzymes [ ] . the initial chest radiographs show minimal abnormality to extensive bilateral infiltrates [ ] . unfortunately, many frontline physicians are unfamiliar with the mers case definition, probably because cases are sporadic, leading to delayed or even missed diagnosis. delayed recognition may lead to exposing many other patients, visitors and hcws to the infection as it was the case in our hospital. mers-cov nosocomial transmission is thought to be via respiratory droplets, and contact spread is suspected [ ] . in korea, the delayed diagnosis of an infected traveler to the arabian peninsula led to mers cases and resulted in intraand inter-hospital transmission [ ] . in saudi arabia, % of mers cases were acquired in the healthcare setting with % of all cases being hcws [ ] . therefore, taking a detailed history, knowing mers case definitions, standardizing pneumonia workup, obtaining lower respiratory tract specimens [ ] and implementing droplet isolation for suspected cases are crucial interventions to break the transmission chain in the healthcare setting. admitting mers patients in single-bedded negativepressure rooms and cohorting them in selected units are recommended to facilitate providing care and monitoring [ ] . during an outbreak, clinical engineering should have expedient plans to convert standard rooms. retrofitting the rooms with externally exhausted hepa filters may be a solution [ ] . outbreaks can lead to significant increase in the need for icu beds, but may simultaneously reduce the available beds. the sars outbreak in toronto led to -day closures of icu beds, which represented % of the tertiary-care university medical-surgical icu beds in toronto [ ] . hence, hospitals should always have plans to augment icu bed capacity, such as by transforming general wards. the ability of any hospital to deal with an infectious outbreak is decided by the availability of icu beds [ ] . caring for mers patients represents a substantial exposure risk for icu staff because of three reasons: high exposure dose, long daily contact hours and prolonged icu stay with viral shedding. mers-cov patients requiring icu admission have higher viral load than other mers patients [ ] . aerosol-generating procedures, such as noninvasive ventilation, suctioning and bronchoscopy, add to the exposure and transmission risk [ ] . extended bedside care is needed for mers patients due to the requirement of organ support such as mechanical ventilation, vasopressor therapy, continuous renal replacement therapy, prone positioning and extracorporeal membrane oxygenation [ , ] . in this study, we observed an increase in the nurse-to-patient ratio from : . to approximately : . during the outbreak. the sars epidemic was also associated with increases in the nurse-topatient ratio [ ] . stay in the icu can last for weeks [ ] , which we observed. additionally, mers-cov shedding can be prolonged and may last for > days [ ] . the exposure risk to mers-cov can exert significant psychosocial stress on hcws. death has occurred in young hcws who acquired mers-cov infection [ ] , which adds to this fear. during the sars outbreak in toronto, a survey of hcws found that > % of respondents reported sars-related concern for their own or their family's health [ ] . moreover, % of respondents had probable emotional distress [ ] . during our outbreak, many icu staff expressed concerns about acquiring mers. staff safety should be a primary goal in a hospital infectious outbreak. pregnant and immunocompromised staff should be redeployed to lower-risk areas [ ] , which we did. proper exposure management should be pre-planned, which was determined in our idep. n respirator fit testing should be performed at hiring of new staff and done for all other staff before any outbreak. although fit testing was required for all staff, many did not have fit testing done. however, in response to the outbreak, fit testing was performed to all staff and powered air-purifying respirators were provided to those who failed fit testing. strict infection prevention and control practices should be implemented and audited. this was performed in our units. repetitive training is recommended [ ] . despite intensive infection prevention practices, of our icu staff had mers-cov infection during the outbreak likely due to suboptimal ppe use while intubating yet undiagnosed patients. mers management was supportive and largely adhered to the who recommendations [ ] . it included intubation, early prone positioning and neuromuscular blockade for moderate-to-severe acute respiratory distress syndrome as these interventions have been shown to improve the outcomes of ards patients [ , ] . although noninvasive ventilation use was discouraged, it was used in patients. the who considers noninvasive ventilation an option in selected mers cases [ ] . it should be used as a short trial without delaying intubation if unsuccessful [ ] . moreover, high-flow oxygen by nasal cannula may be another option [ , ] ; however, the associated transmission risk as a result of aerosol generation is unknown. systematic corticosteroids, ribavirin and interferon were avoided as they have no proven benefit [ , ] . our mers patients had high mortality ( %). the previously reported mortality of mers patients who had critical illness ranged from to % [ , , ] . none of our hcws who developed mers died, which was gratifying to our staff. our mers-cov hospital outbreak stressed our system to unprecedented limits. we learned many lessons from it ( table ). the successful management of outbreak required integrating icu functions with the hospitalwide plans, having preparedness plans, implementing proper infection control practices and managing staffing and staff exposure. every hospital should have an infectious disease epidemic plan that should govern the response to an infectious disease outbreak. the response should cover organizing patient services, implementing infection control, managing employee exposure and communicating with national health services and with hospital staff hospital leaders should be prepared to increase the capacity of negative-pressure airborne infection isolation rooms in the case of an infectious disease outbreak all healthcare workers should receive training on proper hand hygiene and personal protective equipment application. hand hygiene and personal protective equipment practices should be monitored. education should be repeated periodically all healthcare workers should be fit-tested for n respirators on hire with the result documented in their files. periodic audit of this requirement should be done hospitals should make plans to acutely increase personal protective equipment supplies as consumption increases tremendously during an infectious disease outbreak hospital and icu leaders should have plans to cover healthcare workers who are exposed or become symptomatic to avoid potential staff shortage severe acute respiratory syndrome vs. the middle east respiratory syndrome clinical aspects and outcomes of patients with middle east respiratory syndrome coronavirus infection: a single-center experience in saudi arabia clinical course and outcomes of critically ill patients with middle east respiratory syndrome coronavirus infection middle east respiratory syndrome coronavirus hospital outbreak of middle east respiratory syndrome coronavirus mers-cov outbreak in jeddah-a link to health care facilities the national command control center; ministry of health-kingdom of saudi arabia. mers-cov in ksa notes from the field: nosocomial outbreak of middle east respiratory syndrome in a large tertiary care hospital-riyadh, saudi arabia weekend and weeknight admissions have the same outcome of weekday admissions to an intensive care unit with onsite intensivist coverage impact of an intensivist-led multidisciplinary extended rapid response team on hospital-wide cardiopulmonary arrests and mortality a multifaceted approach to improve hand hygiene practices in the adult intensive care unit of a tertiary-care center comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: diagnosis and treatment ministry of health kingdom of saudi arabia. infection prevention and control guidelines for middle east respiratory syndrome coronavirus (mers-cov) infection assays for laboratory confirmation of novel human coronavirus (hcovemc) infections clinical management of severe acute respiratory infection when middle east respiratory syndrome coronavirus (mers-cov) infection is suspected-interim guidance identification and containment of an outbreak of sars in a community hospital middle east respiratory syndrome: knowledge to date middle east respiratory syndrome coronavirus: a case-control study of hospitalized patients stability of middle east respiratory syndrome coronavirus (mers-cov) under different environmental conditions mers outbreak in korea: hospital-to-hospital transmission an appropriate lower respiratory tract specimen is essential for diagnosis of middle east respiratory syndrome (mers) interim infection prevention and control recommendations for hospitalized patients with middle east respiratory syndrome coronavirus hospital preparedness and sars association of higher mers-cov virus load with severe disease and death, saudi arabia aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review clinical review: sars-lessons in disaster management middle east respiratory syndrome coronavirus (mers-cov) viral shedding in the respiratory tract: an observational analysis with infection control implications middle east respiratory syndrome coronavirus infections in health care workers psychosocial effects of sars on hospital staff: survey of a large tertiary care institution sars and hospital priority setting: a qualitative case study and evaluation infection control in the management of highly pathogenic infectious diseases: consensus of the european network of infectious disease prone positioning in severe acute respiratory distress syndrome neuromuscular blockers in early acute respiratory distress syndrome high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: an observational study none. the authors declare that they have no competing interests. written informed consent was not obtained for publication of these data. the institutional review board of the ministry of national guard health affairs approved the retrospective clinical data collection on mers patients, and no consents were required. abbreviations ed: emergency department; hcw: healthcare worker; icu: intensive care unit; idep: infectious disease epidemic plan; mers: middle east respiratory syndrome; ppe: personal protective equipment; rrt-pcr: real-time reversetranscription polymerase chain reaction; who: world health organization. hmd was involved in conception and design, data collection, statistical analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content and approval of the final version to be published. asa contributed to the analysis and interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. rk helped in data collection, analysis and interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. sb contributed to the analysis and interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. jda helped in data collection, interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. aam was involved in data collection, interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. smj helped in data collection, interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. hhb contributed to data collection, interpretation of data, critical revision of the manuscript for important intellectual content and approval of the final version to be published. yma helped in conception and design, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content and approval of the final version to be published. all authors read and approved the final manuscript.author details icu and ticu, intensive care department, king abdulaziz medical city, king key: cord- - mn b vv authors: diehl, j-l; peron, n.; philippe, a.; smadja, d. m. title: response to damiani and colleagues date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: mn b vv nan we have read with great interest the comment of damiani on our article, retaining the hypothesis of a possible major role of microvascular derangement in the physiopathology of covid- ards. such a hypothesis, supported by a number of arguments such as the rich expression of the sars-cov- ace receptors in lung endothelial cells and dysregulation of the renin-angiotensin system, is now widely mentioned by others, using different approaches such as eit studies [ ] , high-energy ct studies [ ] and histopathology studies [ ] . damiani et al. have put our results in perspective with their own published observations of an inverse relationship between sublingual perfused vessel density and d-dimers in mechanically ventilated patients with severe sars-cov- pneumonia. they also reported a tendency to a decrease in sublingual microcirculation in patients with increased driving pressures. interestingly, we observed in our patients an inverse relationship between circulating endothelial cells (cecs) and total respiratory system compliance (r = − . , p = . ), which could suggest a parallel between microvascular and alveolar insults, perhaps in relation with the hemodynamic consequences of a more severe alteration in respiratory mechanics. to explore if covid- ards patients could exhibit a lung-specific microvascular response to high peep levels, as compared to non-covid- ards patients, seems to be an important field of investigation. one important point is that the very vast majority of studies in covid- ards patients used, by convenience, ventilatory ratio (vr) as a marker of impaired ventilatory efficacy, as mentioned in damiani's comment, rather than dead space measurements. however, it must be pointed out that vr was not originally designed to be used as a surrogate of dead space [ ] . accordingly, although highly significant, we found only a moderate level of correlation between vr and physiological dead space (v d /v t ) [ ] . the level was even lower than the values found in the non-covid- ards literature. we appreciate the opportunity to discuss some very important technical points in relation to capnography methods and the derived indexes. damiani et al. state that our v d /v t measurements could be inaccurate, due to transport delay of gas together with variable sampling flow rate. however, this point (and others also considered as disadvantages of the side stream method) is counterbalanced by specific disadvantages of the mainstream method which could also influence the precision of the results. altogether, it is generally considered that there are advantages and disadvantages of both, the choice between them being of personal preference or from availability (as in our cohort of covid- ards) rather than from strong recommendation [ ] . nevertheless, we agree that knowledge of physiologic and technologic basis of capnography is absolutely mandatory, both for research purposes and also for monitoring of icu patients [ ] . finally, it will be important to further precisely investigate the relationship between dead space measurements, with a special focus on indicators of alveolar dead space, and markers of endothelial dysfunction, such as bio-markers (such as cecs and d-dimers) and innovative methods such as the video-microscopy methods used by damiani and colleagues. ideally, such prospective studies should include covid- ards patients and non-covid- ards patients as a control group. they should include measurements performed at different peep levels. they should also include measurements performed during the full course of invasive mechanical ventilation. *correspondence: jean-luc.diehl@aphp.fr potential for lung recruitment and ventilation-perfusion mismatch in patients with the acute respiratory distress syndrome from coronavirus disease pulmonary angiopathy in severe covid- : physiologic, imaging, and hematologic observations pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid- ventilatory ratio: a simple bedside measure of ventilation respiratory mechanics and gas exchanges in the early course of covid- ards: a hypothesis-generating study principles and practice of intensive care monitoring. tobin mj edit an unusual sidestream capnogram publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we would like to acknowledge all nurses, technicians and physicians involved in the george pompidou european hospital for help in taking care of patients and including them in the study. substantial contributions to the conception or design of the work: jld, ds. drafting the work or revising it critically for important intellectual content: all authors. agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors. all authors read and approved the final manuscript. no specific funding. the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. patients mentioned in the response were included in the french-covid national cohort after informed consent of proxies or family members by phone, due to quarantine. additionally, proxies or family members gave also an informed consent by phone for a formalized local process of collecting biological samples in relation to cardiovascular, metabolic or renal diseases (comité de protection des personnes ile-de-france ii, irb registration , approval: november , ). not applicable. key: cord- - hmsknon authors: li, lei; li, ranran; wu, zhixiong; yang, xianghong; zhao, mingyan; liu, jiao; chen, dechang title: therapeutic strategies for critically ill patients with covid- date: - - journal: ann intensive care doi: . /s - - -z sha: doc_id: cord_uid: hmsknon since the novel coronavirus disease (covid- ) outbreak originated from wuhan, hubei province, china, at the end of , it has become a clinical threat to the general population worldwide. among people infected with the novel coronavirus ( -ncov), the intensive management of the critically ill patients in intensive care unit (icu) needs substantial medical resource. in the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of covid- in the icu based on the previous experience of treating other viral infections and influenza. these treatments are referable before the vaccine and specific drugs are available for covid- . in late december , a group of patients with pneumonia of unknown cause were confirmed to be infected with a novel coronavirus ( -ncov) in wuhan, china. the -ncov has now infected tens of thousands of people in china and has spread rapidly around the globe [ ] . the world health organization (who) has declared coronavirus disease (covid- ) as a public health emergency of international concern and released interim guidelines on patient management [ ] . due to the severity and the spreading of covid- (novel coronavirus pneumonia, ncp), the chinese government and the medical institutions have executed strict strategies to control the influence of this epidemic [ ] . until the end of february, the epidemic has been controlled to a great extent nationally. in wuhan, the situation tends to be stable while a high proportion of critically ill patients are still under treatment of intensive care. coronaviruses (covs) are enveloped viruses with a single positive-stranded rna genome (~ - kb in length). covs mainly cause respiratory tract infections and some strains have high infectivity and mortality as well as heavy damage on public health, such as severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers). the -ncov is a β-cov of group b with over % similarity in genetic sequence with sars-ncov [ , ] . the latest version of diagnosis and treatment plan pointed out that the main transmission route is droplet transmission and close contact transmission. in addition, there are risks of airborne spread of -ncov during aerosol-generating medical procedures in specific circumstances [ , ] . for the positive nucleic acid in oropharyngeal swabs. asymptomatic cases also have the risk, although weak, of transmission. respiratory viral infection can cause severe illness, especially in the elderly and persons with co-morbidities [ ] . according to the latest version of diagnosis and treatment guidelines, confirmed cases infected with -ncov are classified to have severe illness once complying with one of the following symptoms: ( ) anhelation, respiratory rate ≥ times/min; ( ) oxygen saturation at rest ≤ %; ( ) pao /fio ≤ mmhg; and classified to be the critical/life-threatening illness once complying with one of the following symptoms: ( ) respiratory failure, mechanical ventilation needed; ( ) shock; ( ) other organ dysfunction syndrome and requirement of intensive care unit admission. the progress of the severe illness with covid- is usually rapid and there is no clear separation between the severe illness and the critical illness. therefore, patients of these two classes are combined to be the critical illness, which is helpful for health care workers to diagnose and treat patients with intensive care and resources at the early stage of the critical illness. the diagnostic evidences for icu admission according to the previous experience in the treatment of sars include old age (> years old), presence of co-morbidities (particularly, diabetes mellitus, hepatic or cardiac disease), and elevated lactate dehydrogenase levels on admission to hospitals [ , ] . -ncov invades through the respiratory mucosa and infects other cells, inducing cytokine storm systemically [ ] . some patients may progress rapidly with ards, disseminated intravascular coagulation (dic), septic shock, and eventually multiple organ failure [ ] . therefore, early identification and timely treatment of critical cases is of crucial importance. evidence-based therapy and supportive care in icu is the mainstay for the management of severe and life-threatening illness of covid- . the severe and critical illnesses with covid- should be treated in icu in the hospital with nosocomial infection control. strict volume management, multi-organ function evaluation, critical care of the nutritional assessment/appropriate nutritional support are essential for these patients in icu. in addition, attention should be paid to bedbound patients to prevent deep vein thrombosis. at present, there is no antiviral treatment with confirmed effectiveness for covid- . available drug options that come from the clinical experience of treating sars, mers and other previous influenza virus have been used for the treatment of covid- patients. although these antiviral drugs are promising in the treatment of covid- , it should be kept in mind that: ( ) the adverse effects of the drugs need to be monitored in clinic, ( ) the effects of these drugs on critically ill patients still need to be clarified, ( ) the potential mutation of the coronavirus may lead to the drug resistance of the virus. nucleoside analogs have a broad-spectrum antiviral effect via the mechanisms of lethal mutagenesis, chain termination, and inhibition of nucleotide biosynthesis. fabiravir and ribavirin are representative drugs of nucleoside analogs and exhibit the antiviral effect by inhibiting nucleotide biosynthesis. it has been demonstrated that the combination of fabiravir and oseltamivir in the treatment of severe influenza may accelerate clinical recovery than oseltamivir alone [ ] . in addition, it has been reported that the combination of ribavirin and interferon alpha (ifn-⍺) significantly reduced the -day mortality of critically ill patients infected with mers, although the -day mortality was not affected [ ] . ribavirin and ifn-⍺ were also used in the treatment for sars. however, ribavirin might have side effects such as anemia and liver injury, and ifn-⍺ may not improve the patients' outcome [ ] . therefore, the use of ribavirin and ifn-⍺ in the treatment of covid- needs to be further elucidated by clinical studies. lopinavir/ritonavir is a protease inhibitor in the treatment of hiv infection. lopinavir/ritonavir showed the antiviral activity by inhibiting the replication of coronavirus in vitro. it has been reported that the combination of lopinavir/ritonavir with ribavirin could lower the risk of ards compared with ribavirin alone [ ] . most recently, the randomized clinical trial of lopinavir/ritonavir ( mg/ mg, twice-daily for days) in the treatment of covid- by cao et al. has shown that in hospitalized adult patients with severe covid- , no beneficial effect was observed with lopinavir/ritonavir treatment compared with standard care group [ ] . the adverse effects of lopinavir/ritonavir treatment include anorexia, nausea, abdominal discomfort, diarrhea, or acute gastritis. moreover, the risk of hepatic injury, pancreatitis, more severe cutaneous eruptions, as well as the drug interactions due to cyp a inhibition has been observed in the clinical trial, which arouses concern about the use of higher or prolonged dose regimens for outcome improvement [ ] . in addition, serious complications such as acute kidney injury and secondary infection were fewer than in those not receiving treatment. future trials with severe illness might help to elucidate the possibility of benefit of lopinavir/ritonavir treatment. remdesivir (gs- ) is a new nucleoside analog and has been recognized as a potential and promising antiviral drug against a wide array of rna viruses, including sars/mers-cov. it is currently under clinical development for the treatment of ebola virus infection [ ] . remdesivir potentially inhibits the rna-dependent rna polymerase from mers-cov, reduces virus replication, decreases the virus titer in mouse lungs infected with mers-cov, and improves the lung tissue damage [ , ] . the antiviral activity of remdesivir and ifn-beta was found to be superior to that of the combination of lopinavir/ritonavir and ifn-beta against mers-cov [ ] . a randomized, controlled trial has reported that the prolonged use of remdesivir in the treatment of ebola virus disease (evd) is safe [ ] , and no adverse events have been observed [ ] . as a candidate drug that has not been approved, information about the side effects of remdesivir has not been reported yet. at present, two randomized, controlled, double-blind clinical trials are ongoing to evaluate the efficacy and safety of remdesivir ( mg loading dose on day , followed by mg i.v. once-daily maintenance dose for days) in hospitalized patients with mild/moderate or severe covid- respiratory disease [ , ] . the results of these clinical trials may open the window for effective antiviral therapy for such an epidemic infectious disease. arbidol is a small indole-derivative molecule and is approved for the prophylaxis and treatment of influenza and other respiratory viral infections [ ] . it also showed inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis b and c [ ] . in addition, arbidol has been reported to have antiviral activity against the pathogen of sars, and the effect of arbidol mesylate-a derivative of arbidol, was almost five times higher than arbidol in reducing the reproduction of sars in cells in vitro [ ] . it has been claimed that arbidol was effective against -ncov in vitro [ ] . a randomized multicenter controlled clinical trial of arbidol in patients with -ncov is in progress in china [ ] . it is known that angiotensin-converting enzyme- (ace ) as a membrane protein is a functional receptor of sars-cov and it can facilitate virus entry into the cells by binding to the spike (s) protein of the virus, which mediates the fusion of viral and host membranes [ ] [ ] [ ] . therefore, it may be of importance to block the binding of s protein to ace to treat viral infection, such as sars-cov [ ] . chloroquine is a -aminoquinoline known since , the sulfate and phosphate salts of which have both been commercialized as widely used antimalarial and autoimmune disease drugs. chloroquine also shows broad-spectrum antiviral effects [ ] . it was found to be a potent inhibitor of sars-cov infection due to its inhibitory effect on ace [ ] . it has been demonstrated that -ncov enter the epithelial cells of oral mucosa via the essential receptor ace [ ] , and chloroquine can function at both entry and post-entry stages of -ncov infection [ ] . besides the antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo. recently, wang et al. have demonstrated that chloroquine is highly effective in the control of -ncov infection in vitro and is suggested to be assessed in human patients suffering from covid- [ ] . in addition, the results from more than covid- patients have indicated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging, promoting virus negative conversion, and shortening the disease course [ ] . however, attention should be paid to the potential detrimental effects of chloroquine observed in previous attempts to treat viral diseases. at present, the clinical trials to evaluate the efficacy and safety of chloroquine in the treatment of covid- is ongoing [ ] . the use of chloroquine in the treatment of covid- should refer to the most recent announcements if any. in addition, hydroxychloroquine is a -aminoquinoline derivative antimalarial drug. hydroxychloroquine is an immunosuppressive drug with mature clinical application in the treatment of rheumatic immune diseases such as rheumatoid arthritis and systemic lupus erythematosus [ , ] . it has been found to be more potent than chloroquine in inhibiting -ncov in vitro. hydroxychloroquine sulfate mg given twice daily for day, followed by mg twice daily for another days is recommended in the treatment covid- [ ] . at present, the clinical evaluation of hydroxychloroquine in the treatment of covid- is in progress [ ] , which might shortly provide preliminary results about the effectiveness of hydroxychloroquine. patients with pneumonia, especially in severe condition, may encounter with co-infection or cross-infection of bacterial pathogens, for instance staphylococcus aureus, during medical treatment in the hospital. considering the high incidence of bacterial infection for critically ill patients with covid- , it is essential to test the kinetics of procalcitonin (pct) and c-reaction protein (crp) in covid- patients for timely diagnosis and intervention of bacterial infection. according to the recent ats/idsa clinical practice guidelines, besides antiviral treatment for patients with viral-infected pneumonia, clinicians should empirically give antibacterial therapy to patients that initially have severe diseases (extensive pneumonia, respiratory failure, hypotension, and fever), or deteriorate after initial improvement, or fail to improve after to days of antiviral treatment [ ] . thus, antibiotic treatment is recommended in the treatment of covid- patients based on the evidence of bacterial infection. the blind and inappropriate use of antibiotics, especially the broad-spectrum antibiotics, should be avoided. immune disorders have been observed in the treatment of patients with covid- . the virus infection activates the immune cells, leading to cytokine storm which is associated with disease severity [ ] . on the other hand, the critical illness with covid- mainly affect elders or people with chronic diseases, some of whom have very low number of lymphocytes, especially cd + t cells, implying deficiency of immune system. therefore, to modulate the immune responses, a variety of pharmacologic agents have been proposed [ , ] . the use of corticosteroids in the treatment of ards is controversial. observational data in sars suggest that immunomodulation with regimens of high-dose methylprednisolone might be helpful in modulating inflammatory responses and lung damage [ , ] . on the other hand, other studies showed that use of steroids is associated with increased risk for bacterial infection, increased mortality, and even antiviral resistance in influenza-associated pneumonia or ards [ ] [ ] [ ] [ ] . moreover, multiple studies have reported that corticosteroid treatment is associated with delayed viral shedding in hospitalized patients without significant change in -day mortality [ ] [ ] [ ] . corticosteroid therapy in patients with mers was shown to be not associated with a difference in mortality, but associated with delayed mers coronavirus rna clearance [ ] .the early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention has been shown to increase the risk for critical disease or death from h n infection [ ] . the currently limited clinical research does not support the use of corticosteroids in the treatment of ards in covid- patients to improve the outcome of patients. the who recommended that corticosteroids should not be used in the treatment of viral pneumonia or ards. there is no convincing proof for the therapeutic benefits of corticosteroids in the treatment of covid- , which still need to be demonstrated in clinical research. thymosin alpha- is a thymic peptide hormone with significant benefits in restoring the homeostasis of the host immune system [ ] . it is chemically synthesized and used in diseases with impaired immune system [ ] . it has been reported that the low lymphocyte count is associated with the poor prognosis of septic patients. the use of thymosin alpha- therapy in combination with conventional medical therapies was effective in improving clinical outcomes and reducing mortality in severe sepsis [ ] . in addition, thymosin alpha- can enhance the immune responses of sars patients and help to limit the spreading of sars [ ] . therefore, although there is no clinical evidence showing the beneficial effects of thymosin alpha- in covid- , it has been recommended to be used for some patients to enhance cellular immunity for the resistance of viral infection. cyclosporine a is widely used in transplantation and autoimmune disorders due to its immunosuppressive effect. cyclophilin a as a key member of immunophilins is the cellular receptor for cyclosporine a [ ] . the inhibition of cyclophilins by cyclosporine a could block the replication of coronavirus, including sars-cov [ ] . therefore, non-immunosuppressive derivatives of cyclosporine a might serve as broad-range cov inhibitors applicable against emerging virus like -ncov, which still needs to be confirmed by clinical studies in the future. there are two types of interferons (ifns), type i ifns and type ii ifns. it has been demonstrated that type i ifns can inhibit the replication of both sars and mers-cov [ , ] . kuri et al. have reported that ifn transcription was blocked in tissue cells infected with sars-cov and cells infected with sars-cov were able to partially restore their innate immune responsiveness to sars-cov after priming with small amounts of ifns [ ] . moreover, in patients with severe mers-cov infection, the combination of ifn-alpha- a with ribavirin was shown to improve survival [ ] . recently, the combination of remdesivir and ifn-beta was shown to have significant antiviral activity [ ] . intravenous gammaglobulin is considered as the safest immunomodulating drug available for the treatment of severe infection and sepsis. it has high titers of neutralizing antibodies against broad-spectrum virus, bacteria, and other pathogens, and can modulate the host immune responses in several ways. however, a large-scale multicenter randomized placebo-controlled trial did not show improved survival with intravenous gammaglobulin in severe sepsis [ ] . moreover, a cochrane review showed that intravenous gammaglobulin did not reduce the mortality of septic patients [ ] . therefore, there is no convincing argument to recommend intravenous gammaglobulin in the treatment of -ncov. one of the most important mechanism underlying the deterioration of covid- is cytokine storm characterized by elevated levels of il , ifn-and other cytokines, which will lead to ards or even multiple organ failure [ ] . tocilizumab is a recombinant humanized monoclonal antibody binding to il receptor and inhibiting its signal transduction. tocilizumab has been used in the treatment for rheumatoid arthritis (ra) [ ] . moreover, tocilizumab has been reported to be effective against cytokine release syndrome induced by car-t cell infusion against b cell acute lymphoblastic leukemia [ ] . in diagnosis and treatment guidelines of ncp (trial version . ) [ ] , tocilizumab is recommended for the immunotherapy of patients with extensive lung lesions and severe cases that show an increased level of il in laboratory testing. the efficacy of tocilizumab in covid- patients still needs to be investigated. in , chinese traditional medicine was used to prevent and treat sars [ ] . in , during the pandemic of h n influenza, the traditional chinese medicine of china issued a chinese traditional medicine prevention program, which included several chinese herbal medicine formulae for the prevention of infection of adults and children. shufengjiedu capsules and lianhuaqingwen capsules have also played a role in the prevention and treatment of new respiratory infectious diseases such as influenza a (h n ) [ , ] . some studies have confirmed that yupingfeng powder has antiviral, antiinflammatory and immunoregulatory effects [ ] . a multicenter, large-scale, randomized trial found that yinqiao powder plus another heat-clearing formula could reduce time for fever resolution in patients with the h n influenza virus infection [ ] . it is suggested that high-risk populations exposed to covid- patients, including medical staff, family members, and other people who are in close contact with covid- patients, as well as residents living in covid- outbreak areas, might benefit from taking chinese traditional medicine formulae for prevention. however, the efficacy and safety of these chinese traditional medicine formulae in covid- need to be further confirmed by clinical trials. the convalescent plasma derived from the patients with antibodies against -ncov can be effective in reducing the mortality rate of critically ill patients with infectious disease [ ] . convalescent plasma has been found to have an immunotherapeutic potential for the treatment of mers, sars and ebola virus disease [ ] [ ] [ ] . the explanation for the efficacy of convalescent plasma therapy is that antibodies from convalescent plasma might suppress viremia via free viral clearance, blockade of new infection, as well as the acceleration of infected cell clearance [ ] . in addition, the use of high-titer mers serum from camel could significantly improve the histology of lung damage and increase the clearance of mers-cov in mice [ ] . moreover, the use of convalescent plasma or serum was also suggested by who under blood regulators network when vaccines and antiviral drug was unavailable for an emerging virus. evidence shows that convalescent plasma therapy is not associated with the occurrence of severe adverse events [ ] . convalescent plasma, if available, can be used for the treatment of critically ill patients with covid- after the evaluation of the valence of antibody. it is worthwhile to test the efficacy and safety of convalescent plasma transfusion in covid- patients. a meta-analysis showed that among patients with -ncov infection, the incidence of ards is approximately % [ ] . moreover, between % to % of patients admitted to icu have hypoxemia/or development of respiratory exhaustion [ ] . therefore, timely and effective respiratory support can contribute to reduce complications and improve the survival of such critically ill patients. oxygen therapy, high-flow nasal cannula, and non-invasive ventilation may reduce the need of endotracheal intubation and decrease ventilator-associated complications and mortality. however, several studies have reported that the failure of non-invasive ventilation was up to % in which invasive ventilation was ultimately required in the treatment of severe influenza a (h n ) in canada [ ] . non-invasive ventilation may be effective and safe for some patients, whereas it might increase virus transmission to health care workers because of risk for infected aerosol generation. therefore, for the treatment of -ncov, non-invasive ventilation may be used in selected patients in early stages with milder acute hypoxemic respiratory failure [ ] . while for critically ill patients, the effectiveness of transitionally oxygen therapy, such as respiratory status and oxygen index (po / fio ), needs to be closely monitored and it should be switched to mechanical ventilation when necessary. high-flow nasal cannula has emerged as an alternative to non-invasive ventilation to prevent intubation and reduce mortality in patients with acute hypoxemic respiratory failure [ ] . high-flow nasal cannula has been reported to significantly reduce -day mortality of community-acquired pneumonia compared with standard oxygen or non-invasive ventilation [ ] . hui et al. have shown that the breath dispersion distance is limited therefore lowering the risk of air transmission. however, the loose connection of the cannula with nasal obstruction can significantly increase the dispersion distance [ ] . wearing masks (particularly n ) can effectively reduce the breath dispersion distance during high-flow nasal ventilation to prevent nosocomial transmission [ , ] . in addition, high-flow nasal cannula might increase virus transmission risk due to aerosol generation. therefore, staff protection of health care workers is critical. mechanical ventilation for patients with severe ards should be managed with lung-protective strategies to minimize ventilator-associated lung injury and to improve survival. the approach to minimize ventilatorassociated lung injury and to improve survival includes: ventilation with low tidal volumes ( to ml/kg of predicted body weight), targeting plateau pressure (< cmh o) [ ] , and minimizing the inspired oxygen concentration to decrease oxygen toxicity. high positive endexpiratory pressure (peep) can reduce the need for high fio by improving gas exchange and lung compliance, whereas too high peep may lead to lung overdistension and hemodynamic instability. optimal peep which can be titrated by pressure-volume curve, oxygenation, stress index, electrical impedance tomography (eit), ultrasound, and some other clinical parameters is associated with improved survival rate among severe ards patients [ ] . lung recruitment needs to be evaluated for mechanically ventilated patients when uncorrectable hypoxemia occurs, and lung recruitment should be executed for patients whose lungs can restore aeration. ct, eit, ultrasound, and other bedside techniques should be used to evaluate lung recruitability before lung recruitment. for critically ill patients managed with mechanical ventilation, excessive spontaneous breathing due to stretching may lead to lung injury. therefore, neuromuscular relaxant may be used to control the spontaneous breathing and protect the lung. prone positioning ventilation is a technique that often improves oxygenation in ards, possibly through improvements in ventilation-perfusion matching, the uniformity of ventilation, and gravity-related atelectasis. prone ventilation was used in mechanically ventilated sars patients without enough data to draw any conclusion with regard to its efficacy [ ] . although prone ventilation showed no improvement in survival or organ dysfunction overall, it might be beneficial for patients with severe ards. a multicenter rct demonstrated that early application of prone positioning in patients with severe ards resulted in decreased mortality [ ] . in addition, the use of prone positioning in patients with h n influenza-induced severe ards was shown to be related with improved oxygenation, sustained after returning to a supine position, and with decreased carbon dioxide retention [ ] . generally speaking, prone positioning ventilation for no less than h daily is a relatively safe procedure that rarely worsens a patient's respiratory status. it can be thus recommended for the treatment of -ncov-induced severe ards. ecmo has become the important life-support strategy for the standardized treatment of ards patients. ecmo should be considered as early as possible when the lung recruitment and prone positioning ventilation show to be ineffective. observational studies have reported that patients with ards induced by h n influenza showed lower hospital mortality with transfer to an ecmo center compared with matched non-ecmo-supported patients [ ] . the use of ecmo also showed survival benefit in patients with severe mers [ ] . ecmo tends to improve patient outcomes when used among those with limited organ failures and good pre-morbid functional status [ ] . substantial proportion of critically ill patients with covid- appear to have developed cardiac arrhythmias or shock [ ] , and may need ecmo support. however, for those who will develop septic shock or refractory multiple organ failure, ecmo is not suggested due to its less benefit. ecmo is a resource-intensive, highly specialized and expensive form of life support with potential for significant complications such as hemorrhage and nosocomial infection. therefore, the use of ecmo should be strictly limited in the treatment of covid- . moreover, since the number of critically ill patients is still increasing and the resource of ecmo is finite, judgment is needed to decide when ecmo may be worthwhile and when it may not. support with ecmo is supposed to be for the most critically ill patients in regions with extensive resources for this therapy [ ] . for patients with ards, restrictive and timely fluid resuscitation is associated with better oxygenation and lower mortality. aggressive fluid administration may worsen oxygenation and ventricular dysfunction, which may result in longer duration of mechanical ventilation and even mortality. therefore, it is necessary to assess fluid responsiveness and to evaluate ventricular function during fluid resuscitation. conservative fluid administration while maintaining adequate mean arterial pressure and organ perfusion with the appropriate use of diuretics and vasopressors is of importance [ ] . according to the latest epidemiological report, the incidence for the critically ill patients to develop multiple organ dysfunction syndrome is up to % [ ] . covid- may be combined with other organ injuries, including liver injury, cardiac dysfunction, coagulopathy, which may need the routine functional support for critically ill patients in icu. moreover, all the critically ill patients with covid- admitted into icu have negative nitrogen balance and malnutrition [ , ] , which has been considered as a contributing factor to the emergence of viral infectious diseases. therefore, appropriate nutritional strategy is pivotal for the treatment of critical illnesses when necessary. there are no specific antiviral drugs or vaccines for -ncov at present. therefore, it is important to enhance the host immune response against the infection with -ncov. all of the drug options are based on the experience treating sars, mers or some other previous influenza viruses. the efficacy of existing drugs as well as adjunctive pharmacologic interventions in the treatment of critical ill patients with covid- warrants further verification in clinical research. to completely stop the epidemic spreading of covid- , a vaccine for -ncov is urgently needed. besides enhancing the host immune responses against viral infection, appropriately respiratory supportive strategies, monitoring and support of multiple organ function, modulating the immune status and inflammatory responses individually, as well as the prophylaxis and treatment of complications are all important guarantee for the recovery of critically ill patients with covid- . for a better understanding of this novel virus, more research needs to be done to get optimal strategies for the treatment of covid- . a novel coronavirus from patients with pneumonia in china organization wh. clinical-management of severe acute respiratory infection when 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summary: tocilizumab for treatment of chimeric antigen receptor t cell-induced severe or life-threatening cytokine release syndrome national health commission & state administration of traditional chinese medicine chinese herbal medicine for severe acute respiratory syndrome: a systematic review and meta-analysis unique synergistic antiviral effects of shufeng jiedu capsule and oseltamivir in influenza a viral-induced acute exacerbation of chronic obstructive pulmonary disease the chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function yu ping feng san, an ancient chinese herbal decoction, induces gene expression of anti-viral proteins and inhibits neuraminidase activity oseltamivir compared with the chinese traditional therapy maxingshigan-yinqiaosan in the treatment of h n influenza: a randomized trial convalescent plasma: new evidence for an old therapeutic tool? convalescent plasma for ebola virus disease retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in sars patients use of convalescent plasma therapy in sars patients in hong kong enhanced clearance of hiv- -infected cells by broadly neutralizing antibodies against hiv- in vivo passive immunotherapy with dromedary immune serum in an experimental animal model for middle east respiratory syndrome coronavirus infection convalescent plasma as a potential therapy for covid- critically ill patients with severe acute respiratory syndrome critically ill patients with influenza a(h n ) infection in canada official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks exhaled air dispersion during coughing with and without wearing a surgical or n mask expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by novel coronavirus pneumonia surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease (covid- ). intensive care med prone positioning in severe acute respiratory distress syndrome a multicenter retrospective review of prone position ventilation (ppv) in treatment of severe human h n avian flu referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza a(h n ) extracorporeal membrane oxygenation for severe middle east respiratory syndrome coronavirus preparing for the most critically ill patients with covid- : the potential role of extracorporeal membrane oxygenation management of critically ill adults with covid- publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors would like to express their appreciation for all of the health care workers and other hospital staff for their efforts in combating the outbreak of covid- . all the authors have participated in literature retrieval and viewpoint discussion. ll and rl have written this article under the supervision of dc and jl. all authors read and approved the final manuscript. not applicable. not applicable. not applicable. the authors declare that they agree for the publication of this article. the authors declare that they have no competing interests. key: cord- -m lkrehi authors: nan title: proceedings of réanimation , the french intensive care society international congress date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: m lkrehi nan introduction: veno-venous extracorporeal co removal (ecco r) is a promising new therapeutic option in the critical care setting. we conducted a prospective observational study of the use of ecco r in selected voluntary centers during years aiming to assess the prevalence of the ecco r use mainly among copd and ards patients. patients and methods: two medical devices: hemolung (alung technologies, pittsburgh, usa) and ila activve (xenios novalung, heilbronn, germany) were selected after literature and medico-economic evaluations. a specific medical and nurses training was provided in table characteristics of patients with known or de novo svv (small-vessel vasculitis) admitted to the intensive care unit for acute respiratory failure (arf) all arf (n = ) immune arf (n = ) non immune arf (n = ) p age , introduction: ineffective triggering is frequent during pressure support ventilation (psv). its occurrence is favored by dynamic hyperinflation that may arise when increasing the pressure support level (psl). decreasing the psl however fails to suppress ineffective triggering in a subgroup of patients that are therefore exposed to refractory ineffective triggering. proportional assist ventilation with load-adjustable gain factors (pav +) decreases the incidence of ineffective triggering in unselected patients but its effect on refractory asynchrony during psv is unknown. the main aim of our study was to assess the effect . the median gain during pav + was % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the asynchrony index was significantly lower with pav + than psv ( % [ ] [ ] [ ] [ ] [ ] [ ] [ ] vs. % respectively, p = . ). moreover, the asynchrony index decreased in every patient with pav + (fig. ) . noticeably, the tidal volume was already protective in psv and decreased even more during pav + ( . ml kg [ . - . ] vs. . ml [ . - . ] respectively, p = . ); and the neural respiratory rate was high in both modes ( cycles min in psv vs. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in pav + , p = . ). total esophageal pressure-time product (ptpes) did not significantly differ between the two modes but the ptpes proportion that was wasted in ineffective efforts decreased with pav + ( % [ ] [ ] vs. % , p = . ). conclusion: our preliminary data suggest that: ( ) pav + reduces the incidence of refractory ineffective triggering; ( ) patients exposed to refractory ineffective triggering during psv seem characterized by rapid shallow breathing despite high ventilatory support, questioning the tolerance of both ventilatory modes. results with further inclusions will be presented. introduction: the use of alternatives to carbapenems to treat patients with extended-spectrum beta lactamase-producing gram negative bacilli (esbl-gnb) infections remains controversial. their use in patients with severe infections in the icu has been poorly studied. the aim of this study was to compare the outcome of icu patients having received carbapenems to those having received a carbapenem-sparing agent (csa). the charts of patients with esbl-gnb infection hospitalized in our icu between and were retrospectively reviewed. patients treated with betalactam betalactam inhibitor (bl bli), cefepime or quinolones were considered has having received an alternative to carbapenems (csa). patients having received such a csa were compared to those having received a carbapenems. primary outcome was treatment failure at day , defined as esbl-gnb infection recurrence (relapse with same pathogen) or death, whichever first occurred. results: patients with esbl-gnb infection were included. source of infection was the lung for most of them. characteristics of patients are displayed on table . their median saps ii and sofa scores were and [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , respectively, and ( %) were on septic shock. patients received a carbapenem empirically, among whom were switched to a csa agent when antibiogram was available (csa-definite group), whereas carbapenems were pursued in the others (carbapenem-only group), mainly because pathogens were resistant to others antibiotics. among the patients having received a non-carbapenem agent as empirical treatment, pathogen was susceptible to this agent in and they pursued the same treatment (csa-only group), whereas were switched to a carbapenem (pathogens resistant to empirical treatment, carbapenem-definite group). treatment failure were not different among these groups (table ) . globally, patients received a csa as their definite treatment (csadefinite and csa-only groups), whereas received a carbapenems (carbapenems-only and carbapenems-definite groups). whereas duration of antimicrobial treatment was similar ( [ - ] days vs. [ - ] days, respectively, p = ns), treatment failure rate was not higher in the former, as compared to those having received a carbapenems ( vs. %, respectively, p = . ). conclusion: treatment of patients with esbl-gnb severe infection in the icu with a csa seems to be safe when the pathogen is susceptible to this csa. however, mic should be first determined before de-escalating to a csa. larger studies are needed. percentages of samplings which attained the pk pd targets for various crcl with potential suboptimal beta-lactam concentration in critically-ill patients with aki treated either with an early or a delayed rrt strategy. patients and methods: ancillary study in a subset of patients with severe aki (kdigo ), receiving a beta-lactam antibiotic, in a trial comparing two rrt initiation strategies. in this trial, patients from intensive care units were randomly assigned to either an early (immediate rrt) or a delayed (late or no rrt) rrt initiation strategy. beta-lactam residual concentrations were sampled at and h after inclusion. the appropriate concentration was defined as a trough of at least times the minimal inhibitory concentration (clinical breakpoint of eucast). the primary outcome was an adequate plasma concentration of the beta-lactam during the first days. results: among the patients included in the centers participating to this ancillary study, a beta-lactam trough concentration was evaluated in subjects, in the early and in the delayed groups. ninety patients ( . %) had an adequate beta-lactam dosage. rrt initiation strategy had no impact on beta-lactam concentration (p = . ). among the septic shock patients ( % of the sampled patients), ( %) had a correct antibiotic concentration. in contrast, only of the patients without definite sepsis ( . %) had a correct dosage. factors associated with an adequate beta-lactam trough concentration in univariate analysis were admission for a septic shock (p = . ), a higher plasma creatinine level (p = . ), a higher mean arterial pressure (p = . ) and a lower serum bicarbonate level (p = . ) at randomization. a higher sofa score was associated with an adequate beta-lactam concentration near to statistical significance (p = . ). multivariate analysis will be presented. in the context of severe aki, beta-lactam concentration reached a sufficient level in % of septic shock patients. interestingly, rrt initiation strategy was not associated with beta-lactam trough concentration. early rrt did not affect trough concentration of betalactam. we may hypothesize that physicians were highly vigilant and adapted antibiotic administration adequately in these patients. introduction: amikacin infusion requires to target a peak serum concentration (c max ) - times the minimal inhibitory concentration, corresponding to a c max at - mg l − for the least susceptible bacteria. recent study reported that % of critically ill patients do not attain this target with a mg kg dose ( ) . membrane sequestration, alteration of the volume of distribution and lack of data in this population make drugs pharmacokinetics (pk) on ecmo challenging. our study aimed to assess the prevalence of insufficient amikacin c max in critically ill patients on ecmo and to identify relative risk factors. patients and methods: prospective, observational, monocentric study of adult patients on venoarterial (va) or venovenous (vv) ecmo receiving a loading dose of amikacin for suspected gramnegative infections. intravenous amikacin was administered with a loading dose of mg kg of total body weight and c max was measured min after the end of the infusion. independent predicators of c max < mg l − after the first amikacin infusion were identified by mixed model multivariate analysis. results: from january to february , patients (median saps (interquartile range) ( - ); age ( - ) years) under va-ecmo ( %) or vv-ecmo ( %) were included. at inclusion, the sofa score was ( - ) and ( %) patients were on renal replacement therapy. overall icu mortality was %. c max was < mg l − in ( %) of the patients. independent risk factors of amikacin under-dosing were body mass index (bmi) < kg m − (odds ratio (or) . , % confidence interval %ci . - . , p = . ) and a positive h fluid balance (or per ml increment: . , %ci . - . , p = . ) (fig. ). our results were comparable to those observed in patients treated with amikacin without ecmo ( ) . conclusion: this large prospective study suggests that the prevalence and associated risk factors of amikacin under-dosing are similar in critically-ill patients with or without ecmo. the use of a mg kg dose in low bmi patients and in those with a positive -h fluid balance on ecmo is strongly encouraged to obtain adequate therapeutic targets and prevent therapeutic failure. results: fifty patients were included ( with delirium, controls), at day for controls and day for patients with confusion. delirium patients were more severely ill sofa [ ; ] versus [ ; ] (p = . ); with higher rass [ ; ] versus [ ; ] (p = . ). they presented with % bl overdosing versus % in controls (p = . ); with % of bl in therapeutic index: % in controls (p = . ). obesity and renal failure were not associated with bl overdosing but there was a trend with hypoalbuminemia (p = . ). discussion: trend in association of bl overdosing with delirium corresponds to previous studies, and would need a larger scale study to be confirmed. severity differences in groups would need changes in inclusion criteria to obtain homogeneous groups. a possible association of bl underdosing with poor evolution of infection and organ failures would need more precise evaluation. hypoalbuminemia could have an impact on bl overdosing. conclusion: delirium was not associated with bl overdosing but with therapeutic index. a high variability of bl concentrations warrants therapeutic drug monitoring. a larger scale study should include changes in design. feasibility and safety of low-flow extracorporeal co removal with a renal replacement platform to enhance lung protective ventilation in patients with mild to moderate ards schmidt matthieu , jaber samir , constantin introduction: extracorporeal carbon dioxide removal (ecco r) might allow ultraprotective mechanical ventilation with lower tidal volume (vt) (< ml kg ideal body weight), plateau pressure (pplat) (< cm h o), driving pressure, and respiratory rate (rr) to reduce ventilator induced lung injury (vili). the aim of this study was to assess the feasibility and safety of ecco r with a renal replacement platform (rrt) to permit ultra-protective ventilation in patients with mild to moderate acute respiratory distress syndrome (ards). patients and methods: twenty patients with mild (n = ) or moderate ards were included. vt was gradually reduced from to , . and ml kg − and peep adjusted to reach > pplat > cm h o. standalone ecco r (no hemofilter associated on the rrt platform) was initiated when arterial paco increased by more than %. ventilation parameters (vt, rr, peep), respiratory compliance, driving pressure, arterial blood gases, and ecco r system operational characteristics (blood flow, sweep gas flow, and co removal rate) were collected during a minimum of h of ultra-protective ventilation. complications, mortality at day , need for adjuvant therapies and data on weaning from both mechanical ventilation and ecco r were also collected. results: while vt was reduced from to ml kg − and pplat kept below cm h o, peep was significantly increased from . ± . at baseline to . ± . cm h o at vt = ml kg − . as a result, the driving pressure was significantly reduced to . ± . cm h o at vt = ml kg − (p < . ) (fig. ) . no significant differences in rr, pao fio ratio, respiratory system compliance were observed after vt reduction. mean extracorporeal blood, sweep gas flow and co removal were ± ml min − , ± . l min − and ml min − , respectively. mean treatment duration was ± h. main side effects related to ecco r were membrane clotting which occurred in patients after ± h. conclusion: a low-flow ecco r device driven by a rrt platform efficiently removed co while allowing ultra-protective mechanical ventilation settings in patients with mild to moderate ards (clinicaltrials. gov identifier: nct ). morimont philippe , habran simon , desaive thomas , janssen nathalie , amand theophile , blaffart francine , dauby pierre , kolh philippe , defraigne jean-olivier , lambermont bernard introduction: protective lung ventilation (plv) is recommended in patients with acute respiratory distress syndrome (ards) to minimize additional injuries to the lung. however, increased right ventricular (rv) afterload resulting from ards could be enhanced by hypercapnic acidosis resulting from ventilation at lower tidal volume. relative contribution of these factors (ards and plv) in rv afterload is not clearly established. the aim of this study was to compare rv afterload in ards combined with plv to rv afterload in plv alone. patients and methods: this study was performed in an experimental model of severe hypercapnic acidosis performed in series of pigs. in both groups, respiratory tidal volume was decreased by %. in the first group (ards group), an ards (obtained by repeated bronchoalveolar lavage) was performed before reducing ventilation, while in the second group (control group), hypercapnic acidosis was resulting from low tidal volume ventilation alone. results: in both groups, systolic pulmonary artery pressure (paps) significantly increased during plv. this increase was significantly higher in ards group than in control group (fig. ) . severe hypercapnic acidosis occurred in both groups: paco increased from . ± . to . ± . (p < . ) and arterial ph decreased from . ± . to . ± . (p < . ) in ards group while paco increased from . ± . to . ± . (p < . ) and arterial ph decreased from . ± . to . ± . (p < . ) in control group. pao significantly decreased in ards group ( ± to ± . mmhg, p < . ) but did not significantly changed in control group. conclusion: isolated hypercapnic acidosis resulting from plv was clearly responsible for increased rv afterload and this effect was significantly enhanced in ards. pulmonary vasoconstriction resulting from hypercapnic acidosis is strongly enhanced by factors like hypoxia, endothelial injuries or inflammatory mediators in ards. extracorporeal co removal could be the solution to limit afterload burden on the right ventricle when plv is achieved during ards. introduction: prone positioning has been shown to improve mortality in acute respiratory distress syndrome (ards) patients. the respiratory system driving-pressure (dprs) and the transpulmonary driving-pressure (dpl), measured with esophageal manometry, have been shown to be strongly correlated with mortality. the aim of this study was to investigate the evolution of the dpl during prone positioning and its relationship with evolution of oxygenation in ards patients. patients and methods: ten patients with ards equipped with esophageal manometry were enrolled. dprs, dpl and chest wall driving-pressure (dpcw) were measured before and h after prone positioning. respiratory system, pulmonary and chest wall elastance (ers, el, ecw) were calculated at the same time. finally, we studied the correlation between these respiratory variables and oxygenation indicators. patients were classified as responders to prone positioning if the change in the ratio of arterial oxygen partial pressure oxygen inspired fraction (delta.pao /fio ) induced by the manoeuvre was larger than the median value observed in the group. results: in the whole population, median value of delta.pao /fio was . mmhg, and patients were classified as responders and as non-responders. in responders, dpl significantly decreased from . ± . cm h o to . ± . cm h o (p = . ) and el decreased from . ± . cm h o l to . ± . cm h o l (p = . ) after prone positioning. other respiratory variables did not change. in non-responders, respiratory variables did not change. between responders and nonresponders, there was no significant difference between baseline respiratory variables. after prone positioning, delta.pao /fio was not related to baseline respiratory parameters. on the contrary delta. pao /fio induced by prone positioning was strongly correlated with changes in dpl (r = − . , p = . ) and changes in el (r = − . , p = . ). we did not find any correlation between delta.pao /fio and changes in dpcw or changes in ecw. the correlation between delta.pao /fio and changes in dprs (r = − . , p = . ) and changes in ers (r = − . , p = . ) did not reach significance. conclusion: in patients who respond to prone positioning by the highest improvement in oxygenation, dpl significantly decrease after prone positioning. the changes in dpl and the changes in el play a major role in the improvement in oxygenation induced by prone positioning whereas the changes in dpcw and ecw do not. introduction: whereas prone positioning (pp) has been shown to improve patient survival in moderate to severe ards patients, its rate of use was . % in lung safe study. however, lung safe study was not specifically focused on pp. therefore, present study aimed to determine prevalence of use of pp in ards patients (primary endpoint), physiologic effects of and reasons for not using pp (secondary end-points). the apronet study was a prospective international one-day prevalence study performed times in april, july, october and january . at each study day, investigators had to screen every patient staying in icu from to h and to fill electronic crf. for patients with ards (defined from the berlin definition criteria) at each study day oxygenation and ventilator settings were recorded. for those receiving pp these variables were recorded before and at the end of pp session. the reasons for not proning were also collected. values are presented as median ( st- rd quartiles). prevalence rates of pp were compared by using chi square for trend and groups were compared with nonparametric tests. introduction: although acute respiratory distress syndrome (ards) has been largely focused on, few data are available concerning hypoxemia independently of its cause in intensive care unit (icu) patients. a recent prevalence-point-day (ppd) evaluated the patterns and outcomes of hypoxemia in french speaking icus. here, we describe the main etiologies, management and outcomes of the patients of this cohort presenting with severe hypoxemia. patients and methods: a ppd was conducted among french speaking icus during spring . hypoxemia was defined by a pao fio ratio below . we analyzed the data from patients with severe hypoxemia (i.e. with a pao fio ratio < ) and compared their characteristics (causes of hypoxemia, ventilatory and non-ventilatory management) and outcomes to the patients with mild or moderate hypoxemia. results: among the hypoxemic patients the day of the study, ( %) had severe hypoxemia. the main cause of hypoxemia was pneumonia and this diagnosis was more frequent than in mild and moderate hypoxemia. whereas bilateral radiologic infiltrates were present in ( . %) patients, ards was diagnosed by physicians in only ( . %) of them. invasive mechanical ventilation (mv) was used in ( . %) patients. high flow oxygen was administered in ( . %) of them and ( . %) were under non-invasive ventilation (niv) the day of the study. median vt was . ( . - . ) ml kg of ibw. positive end-expiratory pressure (peep) was higher than in mild and moderate hypoxemic patients ( ( - ) vs. ( - ) and ( - ) cm h o respectively, p < . ). median plateau pressure was . ( - . ) and was higher than in mild and moderate groups. median driving pressure was ( - ) cm h o with no difference when compared to other groups. neuromuscular blocking agents were administered in ( . %) patients, inhaled nitric oxide (ino) in ( %) patients and only patients ( . %) were on prone positioning. fourteen ( . %) patients were under extracorporeal membrane oxygenation (ecmo). icu mortality was higher in severe hypoxemic patients as compared to mild and moderate ( . vs. . and . % respectively, p < . ). icu length of stay in icu survivors was not statistically different between groups. conclusion: severe hypoxemia, independently from ards, worsens the prognosis of icu patients. even though ards might be underdiagnosed, a protective ventilation was respected in severe hypoxemic patients. introduction: major changes in septic shock management raise the questions of the relevance of the classical risk factors of nosocomial infections in the current era and the link with the primary infectious insult. we herein investigated the risk factors and the outcomes of icuacquired infections in a recent cohort of septic shock patients. patients and methods: this was a -year ( - ) monocenter retrospective study. all adult patients diagnosed for septic shock within the first h were included. septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. patients who survived the first three days were eligible for assessment of the risk of the first icu-acquired infections. the diagnosis of nosocomial infections were based on current international guidelines. patients were classified according to the development of pulmonary or non-pulmonary icu-acquired infections. the determinants of icu-acquired infections were addressed in a multivariate logistic regression analysis. results: patients were admitted for septic shock. patients remained alive in the icu after the first three days and could then be evaluated for the risk of icu-acquired infections. hence, patients remained free of secondary infections, patients first developed an episode of nosocomial pneumonia and patients first developed an episode of non-pulmonary infection. the mortality rates of patients with icu-acquired pneumonia, non-pulmonary icu-acquired infections and without secondary infections were , and %, respectively (p = . ). in multivariate analysis, the development of icu-acquired pneumonia was independently associated with male gender (or . , ci % [ . - . ], p = . ), renal replacement therapy (or . , ci % [ . - . ], p = . ), platelet transfusion (or . , ci % [ . - . ], p = . ) and a primary pulmonary infection (or . , ci % [ . - . ], p < . ). the development of non-pulmonary infections was independently associated with renal replacement therapy (or . , ci % [ . - . ], p < . ), fresh frozen plasma transfusion (or . , ci % [ . - . ] , p = . ), healthcare-associated septic shock (or . , ci % [ . - . ], p = . ). conclusion: icu-acquired pneumonia occurs preferentially in patients with septic shock of pulmonary origin. in addition, we identified the transfusion of blood products as a risk factor for pulmonary and nonpulmonary nosocomial infections. introduction: human serum albumin is used for the restoration of blood volume, emergency treatment of septic shock patients. several experimental studies suggested that albumin could have additional protective effects on the vascular wall and more specifically on endothelial functions. however, the in vivo effect of albumin in human endothelium remains unknown. the aim of this study is to assess the effect of albumin or saline infusion on skin endothelial function in septic shock patients requiring volume expansion. we performed a prospective randomized monocentric study in an -bed medical intensive care unit. all patients with septic shock who required fluid administration were included between h and h after vasopressor starting. patients were randomized to receive either ml of saline solution . % or ml of albumin %. norepinephrine dose was not modified h before and during the procedure. endothelium-dependant vasodilatation in the skin circulation was assessed by iontophoresis of acetylcholine before and after fluid administration. the improvement of skin blood flow in response to acetylcholine after fluid administration was compared between groups. for each patient, age, sex, saps ii, site of infection, global hemodynamic parameters and clinical microcirculatory parameters were recorded. results are expressed as mean ± sd. qualitative data were compared using chi- or fisher's exact test while quantitative data comparisons used student t test or mann-whitney as appropriate. results: twenty-two patients were included ( women, age: ± , saps ii: ± ). twelve patients received saline and received albumin. apart from age, no statistical difference was found between groups regarding demographic characteristics and baseline hemodynamic parameters. norepinephrine dose and mean volume of infused fluid before inclusion was not different between groups (table ) . before fluid replacement, endothelial response to acetylcholine iontophoresis was not different between groups (auc vs ; p = . ). volume expansion induced a slight increase of systolic arterial pressure, significantly higher in the albumin group ( vs %; p = . ) with no difference regarding cardiac output variations between groups. next, we compared the variations of endothelium response to iontophoresis before and after fluid infusion. the improvement of endothelial response after acetylcholine challenge was significantly higher in the albumin group ( vs %, p = . ). conclusion: in the early stage of septic shock resuscitation, we showed that albumin infusion had protective endothelial effects. this result has to be confirmed in a larger cohort. ] + all p < . ). we found no correlation between cognitive scores at hospital discharge and the severity of eeg-defined encephalopathy during the days of icu or during the first h after admission. however, sepsis survivors' scores were lower than controls' (p < . ) ( table ) . conclusion: in this study, eeg was more sensitive than clinical tools to detect sae but clinical scales correlated with the eeg grade. encephalopathy was not associated with short-term cognitive function. further study and a larger cohort are needed to determine which early eeg introduction: there is growing evidence that corticotherapy improves survival from septic shock. this observational study aimed at evaluating at bedside resistance to corticosteroids in adults with sepsis. patients and methods: participants-icu adults with septic shock or without sepsis admitted to the raymond poincaré university hospital. we also evaluated healthy controls. intervention-resistance to corticosteroids was assessed using a skin test. µl of dermocorticoid cream (class iii, betamethasone) was applied on a cm surface of the skin. at h, two independent physicians scored the blanching of the skin from to - -no blanching + -< % of surface + - to % of surface + - to % of surface, and -blanching beyond application area. cohen's kappa was used to measure concordance. a mean score of < indicated corticoresistance and a score of indicating normal sensitivity to corticosteroids. we also performed a µg acth test. results: we enrolled patients, patients with septic shock ( males, ) and patients without sepsis ( males, ). overall, ( %) with two measurements patients had concordant evaluation of score by the two physicians + while had a difference of -point in scores, resulting in a kappa of . ( % ci . - . ). in patients with septic shock, ( %) have corticoresistance, i.e. a mean score < , ( %) a score of or , and ( %) has normal sensitivity to corticosteroids. in non-septic critically ill, ( %) have corticoresistance, ( %) a mean score of - , and ( %) have normal sensitivity to corticosteroids. hence, as compared to non-septic patients, patients with septic shock were more likely to have corticoresistance (p = . ). discussion: topic application of corticosteroids on the skin results in activation of glucocorticoid receptors present within the vessels. subsequently, activation of lipocortin may inhibit the activity of phospholipase a , regulator of prostaglandins, leucotrienes and platelet activating factor. then, the coupling of alpha adrenoreceptors to their agonists is potentiated, increasing vessels smooth muscles sensitivity to catecholamines. the subsequent local vasocontriction is reflected by skin blanching. thus, the observed lack of skin blanching in septic patients may reflect altered coupling between gluocorticoids and glucocorticoids receptors. conclusion: roughly one out of two adults with septic shock may develop a resistance to corticosteroids as assessed by a skin blanching test in response to betamethasone. introduction: mild therapeutic hypothermia, currently recommended in the management of cardiac arrests with shockable rhythm could promote infectious complications and especially ventilator-associated pneumonia (vap) (mongardon et al. crit care med ). despite high incidence of vap and retrospective trials suggesting a benefit of shortterm ( h) antibiotics in this setting (davies et al. resuscitation ) , systematic use of antibiotic prophylaxis is not recommended in patients treated with mild therapeutic hypothermia after cardiac arrest. the primary objective was to demonstrate that systematic short-term antibiotic prophylaxis with amoxicillin-clavulanic acid can reduce incidence of early vap (< days) in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest. secondary objectives were its impact on incidence of late vap and on day mortality. patients and methods: multicenter two parallel-group doubleblinded randomized trial. adult patients hospitalized in icu, mechanically ventilated after out-of-hospital resuscitated cardiac arrest related to initial shockable rhythm and treated with mild therapeutic hypothermia were eligible. exclusion criteria were pregnancy, need for extracorporeal life support, ongoing antibiotic therapy or pneumonia, known chronic colonization with multiresistant bacteria, known allergy to beta-lactam antibiotics and moribund patients. patients received either intravenous injection of amoxicillin-clavulanic acid ( g mg) or placebo three times a day for days. the primary endpoint was the onset of early vap. all suspected pulmonary infections were adjudicated by a blinded independent committee. results: out of patients included, were finally analyzed, in treatment group and in placebo group (mean age . ± . years, sex ratio = , sofa score . ± . ). characteristics of cardiac arrest were similar in both groups (no flow = . ± . min vs . ± . min, low-flow = . ± . min vs . ± . min). early vap were confirmed, in treatment group vs in placebo group, with an incidence of . vs . %, respectively (hr = . + ic % = [ . + . ], p = . ) (fig. ). the procedure did not affect occurrence of late vap (> days), respectively vs . day mortality was similar in both arms ( . vs . %, p = . ) and no adverse event was related to study treatment. conclusion: short-term antibiotic prophylaxis with amoxicillin-clavulanic acid significantly decreases incidence of early vap in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest related to shockable rhythm. introduction: immunosuppressed (is) patients are prone to develop respiratory failure and to need ventilatory support. invasive ventilation shared a grim prognosis in the past and non-invasive ventilation had been recommended in these patients, however niv efficacy has been recently challenged and the advent of high flow oxygen therapy had brought even more complexity in the management of such patients. using the data from a recent point-prevalence-day of hypoxemia in icu, we compare the frequency, management and outcomes of hypoxemia in is and immuncompetent (ic) patients. patients and methods: the spectrum study was conducted in french-speaking icus in countries during spring . is was retained in case of malignant hemopathy, hiv positivity, immunosuppressive drugs, recent chemotherapy, neutrophil count < . g l. hypoxemia was defined as a pao fio ratio > and separate into severe (> ), moderate (> ) and mild (> ). we focused on the causes of hypoxemia, the ventilatory management and the outcome. results: among the patients included, ( %) were is out of whom ( %) were hypoxemic, proportion similar to the ic patients. mean age and igs- of hypoxemic patients were similar in is and ic patients. hypoxemia was mild in ( %), moderate in ( %) and severe in ( %) is patients with a similar distribution compared to hypoxemic ic patients. the causes of hypoxemia were also similar pneumonia being the leading cause. ( %) hypoxemic is patients fulfilled the berlin criteria for ards in a similar proportion to ic patients. respiratory support used in hypoxemic is patients was ambient air in , low flow oxygen in , high flow in , niv in and invasive ventilation in patients, with a different distribution from the ic patients (more patients on high flow therapy and less invasively ventilated). the day of the study, thoracic ct scan and echocardiography were performed in a similar proportion in is and ic patients whereas broncho-alveolar lavage was more frequently performed in is patients ( vs %, p < . ). finally, as expected, icu mortality was higher in hypoxemic is patients ( vs %, p < . ). conclusion: immunosuppression in the icu seems not to be associated with hypoxemia, severity of hypoxemia or ards. oxygenation management is slightly different from immunocompetent patients with more frequent use of high flow therapy. ( ) mmhg, ph . ( . ). were included in the l/kg/min group and in the l/kg/min group. no difference was observed between groups for baseline characteristics. failure rate was not different between groups- . vs . % + p = . . no center effect was observed for failure. discomfort was more frequent in the l kg min group- vs % + p = . . the length of stay was shorter in the l kg min group- . ( . ) vs . ( ) days + p = . . intubation occurred in patients in the l/kg/min group vs patients in the l kg min group (p = . ). conclusion: hfnc with a flow rate of l/kg/min did not reduce the risk of failure compared to l/kg/min at the initial respiratory management of avb in young infants. comparison of epinephrine and norepinephrine for the treatment of cardiogenic shock following acute myocardial infarction. optima cc study levy bruno introduction: despite the frequent use of vasopressors which are administered in % of patients in cardiogenic shock (cs), there is only limited evidence from randomized trials comparing vasopressor in cs. hence, the optima cc study was designed to compare epinephrine and norepinephrine in cardiogenic shock following myocardial infarction. patients and methods: multicenter, double-blind, randomized trial in french icu. cardiogenic shock patients due to myocardial infarction treated by pci were randomized to receive epinephrine or norepinephrine to maintain map at mmhg. dobutamine was introduced at the physician discretion according to a combination of parameters-echocardiographic parameters, cardiac index, lactate clearance, svo and swan-ganz derived parameters. results: / patients were ventilated ( %). there were no differences in the duration nor in the maximal dose or cumulated dose of epinephrine or norepinephrine. dobutamine was used in / ( %) in the epinephrine group and in / ( %) in the norepinephrine group. there were no differences in the duration, in the maximal or cumulated dose. arterial pressure evolution was similar. heart rate increased significantly in epinephrine group and did not change in norepinephrine group. cardiac index and cardiac power index increased significantly more in the epinephrine group than in the norepinephrine group. cardiac double product, a surrogate of myocardial oxygen consumption increased in epinephrine group and did not change in norepinephrine group. epinephrine use was associated with a lactic acidosis from h to h while arterial ph increased and lactate level decreased in norepinephrine groupepinephrine was significantly associated with an higher incidence of refractory shock- / ( %) versus / ( %) p = . ). the incidence of arrhythmia was identical (epinephrine- % versus norepinephrine- %, p = . ). ecmo was used in / ( %) in the epinephrine group and in / ( %) in the norepinephrine group (p = . ) mortality was / ( %) in the norepinephrine group and / ( %) in the epinephrine group (p = . ) epinephrine use was associated with a trend to an increased risk of death (p = . ) and an increased risk of death plus ecmo (p = . ) at days. there was a trend for an increased risk of death plus ecmo at j (p = . ). conclusion: in patients with cardiogenic shock following myocardial infarction, epinephrine use was associated with a lactic acidosis, an higher incidence of refractory shock and an increased risk of death plus ecmo at j . high dose immunoglobulins in toxic shock syndrome in children: a pilot randomized controlled study (ighn study) javouhey etienne , leteurtre stéphane , tissières pierre , joram nicolas , wroblewski isabelle , ginhoux tiphanie , dauger stéphane , kassai behrouz hôpital mère enfant, bron, france; hôpital jeanne de flandre, lille, france; hôpital du kremlin-bicêtre, le kremlin-bicêtre, france; chu nantes, nantes, france; chu grenoble, la tronche, france; hospices civils de lyon, bron, france; hôpital robert debré, paris, france; hospices civils de lyon, bron, france correspondence: javouhey etienne -etienne.javouhey@chu-lyon.fr annals of intensive care , (suppl ):co- introduction: superantigen toxins synthesized by s. aureus or by s. pyogenes are responsible for toxic shock syndromes (tss) which lethality can reach %. high dose intravenous immunoglobulins (ivig), able to neutralize these toxins, are frequently used even tough evidence of its efficacy is not supported by randomized controlled study (rct) . moreover, ivig are expensive and possibly harmful. before conducting a rct, a pilot study was first designed to assess the feasibility in the context of pediatric critical care. patients and methods: a double blinded rct was performed comparing g kg of ivig to isovolumic % albumin perfusion within the first h of tss in children aged between month to years. a priori criteria to determine the feasibility were defined as a rate of inclusion among eligible patients > %, a rate of protocol's deviations < % (treatment delivery, non-respect of blinding, premature stop), and by the practical and financial aspects of the protocol. secondary objectives were to assess the efficacy of ivig on organ dysfunction (using pelod- score), on mortality at day and their safety. the study was promoted by the hospices civils of lyon, approved by the cpp sud-est and registered at clinical trial (nct ). inform consent from both parents was required before randomization. this study was funded by csl-behring company. results: during the months study period, patients were included in centers. the inclusion rate was of % ( parent's refusals, parents were absent at admission). two patients were wrongly included (pneumococcal shocks), one patient didn't receive the treatment because he was transferred for ecmo in a non-investigator center, three patients were treated after h, and in two patients one bottle of treatment was missing. the blinding was well respected. missing data on the pelod score and mortality was lower than %, and no premature stop was reported. the ecrf completion was judged easy by investigators. the inclusion of children within the first h was judged challenging. the treatment delivery had to be improved, requiring the help of research assistants. seven serious and one severe adverse events were registered, all patients recovered and no death was reported. conclusion: this pilot study suggested that a rct is feasible. it provides crucial information to improve the recruitment, the respect of the protocol and the correct measure of organ failure. however, inclusion of international centers is necessary to attain the sample size required. indirect calorimetry-based method for the work of breathing assessment when compared to esophageal pressure (pes) measurement and electrical activity of the diaphragm (eadi) during a spontaneous breathing trial in continuous positive airway pressure. patients and methods: a prospective single center study. all intubated and mechanically ventilated children > months and < years old, hospitalized in the pediatric intensive care unit were eligible. patients considered as ready to extubate were included. simultaneous recordings of vo , pes and eadi were performed during steps: before, during and after the spontaneous breathing test in continuous positive airway pressure. results: twenty patients, median . months, were included. half of the patients were admitted for a respiratory reason. predicted resting energy expenditure was overestimated as compared to measured resting energy expenditure ( [ - ] vs [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] kcal kg day, p < . ). spontaneous breathing test was associated with an increase in esophageal pressure-time product from to cm h o s min. the same trend was observed in respiratory drive, assessed by eadi which increased from . [ . - . ] to . [ . - . ] . oxygen consumption obtained by ic was higher during spontaneous breathing test as compared to conventional ventilation ( . [ . - . ] vs . [ . - . ] ml kg min) but non significantly. changes in work of breathing as assessed by vo was poorly correlated with measurements from pes and eadi whereas we found a moderate correlation between pes and eadi values. spontaneous breathing test and extubation were successful in ( %) and ( %) patients, respectively. conclusion: during weaning from mechanical ventilation, spontaneous breathing test in continuous positive airway pressure induced an increase in work of breathing, both in respiratory drive, as measured by eadi and in respiratory mechanics, as measured by pes. oxygen consumption measured by indirect calorimetry does not seem to be a reliable tool to assess work of breathing in mechanically ventilated children. ben gheriba khalil , grimaud marion , heilbronner claire , roy emeline , hadchouel alice , renolleau sylvain , rigourd virginie hôpital necker enfants malades, paris, france correspondence: ben gheriba khalil -bg.khalil@gmail.com annals of intensive care , (suppl ): introduction: during the winter season - we had evaluated breastfeeding disruption after hospitalization for bronchiolitis in our hospital in infants under month (n = ). we observed % of mothers whose breastfeeding was stopped of modified. clinical severity had no impact on breastfeeding but % of mothers stated that lack of support and advice was the first cause of breastfeeding disturbance. we conducted this second phase to evaluate the potential impact of actions to promote breastfeeding on unwanted weaning during hospitalization for bronchiolitis. patients and methods: this is a cross sectional study during two epidemic seasons of bronchiolitis in a tertiary care hospital. all patients aged months or younger hospitalized with acute bronchiolitis and receiving at least partial breastfeeding were eligible for the study. patients discharged at home whose parents accepted to be contacted by phone were included. a bundle of actions to promote breastfeeding in patients with bronchiolitis was implemented (posters, flyers, staff training, equipment with breast pumps) between the two epidemic seasons. the data was extracted from the charts and from a phone survey two weeks after discharge to evaluate breastfeeding in eligible patients in our hospital. phase i (before action) had included patients hospitalized between december and march in all wards hosting patients with bronchiolitis. phase ii (after action) included patients hospitalized from october to december . the data from phase ii was compared with data from phase i. results: fifty patients could be included during the second step of the study, with a mean age of days. breastfeeding was exclusive for % of mothers (vs % in phase i). the median length of stay was days (vs days in phase i). twenty-one ( %) patients spent time in picu vs. % in phase i, needed intubation, received non invasive ventilation for a median length of days (vs. days in phase i). the number of patients needing nutritional support was ( %) during phase ii vs. ( %) during phase i. after implementation of our actions, ( %) mothers kept breastfeeding as before (vs. % in the previous epidemic season, p < . ), mothers ( %) stopped, ( %) switched to partial breastfeeding and ( %) reduced without stopping. conclusion: bronchiolitis is a high risk event for breastfeeding disruption but staff training and correct advices and support for mothers during hospitalization seems to diminish that risk. benefits of using a high temporal resolution database in the automatic real-time pediatric ards screening nardi nicolas introduction: pediatric acute respiratory distress syndrome (pards) is frequent in pediatric intensive care units (picu), potentially lethal and the diagnosis is often missed or delayed (palicc ) . in picu, data are usually recorded between to min which leads to only a minority of the arterial partial pressure of oxygen (pao ) that are usable to calculate a valid oxygenation index (oi). if not available, pao should be replaced by the spo if < % to calculate the oxygen saturation index (osi). using a high temporal resolution (htr) database that records data every - s, we aim to develop a relevant clinical algorithm of mass data aggregation to improve pards screening with the automatic oi and osi calculation. patients and methods: all the patients admitted to our pediatric icu between may and august were included. the htr and the electronic medical records (emr) were queried through structured query language (sql) following these steps-( ) data selection ( ) extraction to a linear format ( ) date and time synchronization ( ) data pivoting ( ) aggregation through a -min moving average ( ) hypoxemia calculation. statistical analysis included proportions, correlations and bland-altman analysis. results: between may and august , patients ( stays) were admitted to the picu. approximately million rows were retrieved from the databases including , pao values. the algorithm was able to calculate , ( % of the pao ) oi and osi. the comparison between oi and osi showed that . % of the results were between the limits of agreements (− . + . ), a bias of − . and a correlation r = . . the comparison between the ois from the htr and emr databases showed that . % of the results were between the limits of agreements (− . + . ), a bias of − . and r = . . conclusion: using a mass data aggregation algorithm on a htr database allows more pao to be used to calculate an oi than the usual emr. the oi results differ slightly between the htr and the emr. the accuracy is probably in favor of the htr because of the shorter timelapse between the oi parameters. the osi is possibly a biased oi surrogate and should be interpreted with caution. our next step will be to measure the impact of the algorithm on the pards real-time diagnosis and pards severity categories. introduction: early administration of appropriate antibiotic therapy with adequate concentration is the cornerstone of the severe sepsis and septic shock's treatment. adult studies showed alteration of distribution and elimination which can lead to insufficient drug concentration in septic patients. in children, studies are lacking and antibiotic dosing may be suboptimal. we aim to describe the plasma concentration of the most used beta-lactam in critically ill children, to describe the rate of patients with suboptimal exposure and associating clinical and biological factors. patients and methods: this was a prospective, single center, observational study designed in beds pediatric intensive care unit (picu) and high dependency care at the necker hospital (paris, france) from january to may . were included, children with severe sepsis or septic shock, aged less than years and weighing more than . kg, and receiving one or more of the following antibiotics-amoxicillin, cefotaxime, cefazolin, ceftazidime, piperacillin-tazobactam, meropenem and imipenem for suspected or proven infection. betalactam plasma concentrations were analysed using high performance liquid chromatography. results: we enrolled children (severe sepsis, n = ( . %) + septic shock, n = ( . %)) with a median age of months ( - . bacteria were identified in patients ( . %). a total of blood samples were analysed at a median of days ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) following the onset of sepsis. twenty-four patients ( . %) had insufficient concentration (cefotaxime ( %) + piperacillin-tazobactam, ( %) + amoxicillin ( %) + meropenem ( %), cefazoline ( %), imipenem ( %) + ceftazidime ( %)). insufficient concentrations were associated with early measurements (< h from the sepsis' onset) (p = . ) and creatinine clearance increase (p = . ). adequate concentrations were associated with small age (p = . ). in conclusion, current standard beta-lactam dosing in children with severe sepsis or septic shock could be inadequate to reach the target concentrations. that could lead to the risk of clinical and bacteriological failures as well as the emergence of bacterial resistance. further pharmacokinetic studies are mandatory to improve antibiotic therapy in this vulnerable population. introduction: intermittent hemodialysis is a key support therapy in icu. despite protocol-based optimization, intradialytic hemodynamic instability (ihi) remains a common complication and could account for mortality and delayed renal recovery. the identification of patients at high risk for ihi is crucial but remains poorly explored. our objective was to test whether tissue perfusion parameters assessed at the bedside (mottling, index capillary refill time (icrt), and lactate) predict ihi and to develop and to validate a predictive score of ihi. patients and methods: prospective observational study in a -bed medical icu in a tertiary university hospital including hemodialysis sessions performed for acute kidney injury. exclusion criteria were patients with dark skin and dialysis performed in extreme emergency. mean arterial pressure (map), mottling score, icrt, and lactate were recorded just before starting hemodialysis. first episode of ihi requiring therapeutic intervention was recorded , , and min after hemodialysis starting. results: ninety-six hemodialysis sessions performed in patients were recorded. half of the patients received vasopressors (n = , %). ihi occurred in ( %) sessions and was more frequent among patients receiving vasopressors ( vs %, p < . ). mottling were more frequent ( vs %, p = . ), lactate levels higher ( . [ . - . ] vs . [ . - . ] mmol l, p < . ) and icrt longer ( . [ . - . ] vs . [ . - . ] s, p < . ) before sessions with ihi compared to sessions without, independently of map (p < . ). the incidence of ihi increased with the number of tissue perfusion alterations ( , , , and % for , , , and alterations, respectively, p < . ). a tissue hypoperfusion score, defined as icrt (seconds) + lactate level (mmol l) + if mottling presence was predictive of ihi independently of map (or . [ . - . introduction: epidemiological data suggest an increased risk of longterm chronic kidney disease after acute kidney injury (aki). in survivors of out-of-hospital cardiac arrest (ohca), aki is frequent and is associated with numerous factors of definitive renal injury. we made the hypothesis that aki after ohca was a strong risk factor of long-term chronic kidney disease (ckd). we aimed to evaluate renal outcome of ohca survivors according the occurrence of aki in icu. patients and methods: we used the cohort of consecutive ohca patients admitted between and in a tertiary medical icu previously described (geri et al. icm. ) . aki was defined by kidney disease improving global outcomes (kdigo) criteria. long-term creatinine level was the last blood creatinine assessment we were able to retrieve. the main outcome was the occurrence of ckd, defined by an estimated glomerular filtration rate (egfr) lower than ml min . m according to the mdrd equation. long-term mortality was evaluated as well. factors associated with ckd occurrence were evaluated by competing risk survival analysis (fine gray and cox cause specific models providing sub-hazard ratio (shr) and cox sub-hazard (csh)). results: among the ohca patients who were discharged alive, we were able to retrieve the outcome of patients (median age [iqr , ] , . % of male) who were included in the analysis. during a median follow-up time of . [ . - . ] years, ckd occurred in ( . %) patients and ( %) patients died. a previous history of arterial hypertension (shr = . [ . + . ], p = . + csh = . [ . + . ], p = . ), aki during icu stay (shr = . [ . + . ], p = . + csh = . [ . + . ] , p = . ) and an age higher than (shr = . [ . + . ] , p = . + csh = . [ . + . ], p = . ) were independently associated with ckd occurrence. aki was not associated with long-term mortality (shr = . [ . + . ], p = . + csh = . [ . + . ], p = . ). in ohca survivors resuscitated from an ohca, ckd was a frequent long-term complication. aki during icu stay was a strong determinant of long-term ckd occurrence. introduction: many critically ill patients have a moderate to high risk of bleeding but they also require prolonged intermittent dialysis to ensure a negative water balance without hemodynamic adverse events. thus, a heparin-free easy-to-use anticoagulation within the dialysis circuit is needed but, to date, usual protocols (iterative saline flushes, heparin grafted membranes) lead to - % of premature clotting and sessions that last greater than min are rarely achievable. we assessed the safety and efficiency of heparin-free regional citrate anticoagulation of the dialysis circuit using a calcium-free citrate-containing dialysate, with calcium reinjected according to ionic dialysance (an online measure of the instantaneous clearance of small molecules available in most of dialyzers). patients and methods: we prospectively reported the clotting events that occurred during all the heparin-free dialysis sessions that were performed with a regional anticoagulation based on calcium-zero citrate-containing dialysate (citrasate, hemotech, france) between january and august in a -beds icu. results: a total of dialysis sessions were performed in patients (mechanical ventilation n = + norepinephrine n = ). median duration of dialysis was min (iqr, - + maximum min), and median ultrafiltration volume was l (iqr . - . ). when assessed, urea and beta -microglobulin reduction rates were . % ± . % and % ± . %, respectively. postfilter ionized calcium was . ± . and . ± . mmol l at and h, respectively, within the extracorporeal circuit. a major clotting event that led to premature termination of the session occurred in only sessions ( . %) . in these five cases, major catheter dysfunction occurred before clotting within the circuit. prefilter ionized calcium remained within narrow ranges (before after change + . ± . mmol l), and total-to-ionized calcium ratio, a surrogate marker for citratemia, was unchanged and always below . . in sessions, no ionized calcium measurement was required. conclusion: dialysis anticoagulation with calcium-free citrate containing dialysate is an easy-to-use, efficient, and inexpensive form of heparin-free regional anticoagulation. calcium reinjection according to ionic dialysance allows prolonged hemodialysis sessions in critically ill patients without the need to systemically monitor ionized calcium. sessions can be safely extended according to the hemodynamic tolerance to ensure an adequate dose of dialysis and a negative water balance, a major point in patients with severe aki. introduction: brain injury is the first cause of death after cardiac arrest (ca) and multimodal neuroprognostication is a cornerstone of postresuscitation care. among the different usable information provide by electroencephalogram (eeg), the aim of this study was to evaluate the predictive value of eeg reactivity regarding neurological outcome at discharge. patients and methods: using our prospective registry of successfully resuscitated patients admitted to a cardiac arrest center between january and , we studied all consecutive comatose patients still alive at h and in whom at least one eeg was performed during coma. in addition to usual clinical findings, we collected eeg (patterns and reactivity, status epilepticus) and somatosensory evoked potentials characteristics. the eeg reactivity was evaluated by a blinded neurophysiologist and was defined as a reproducible change of the tracing (in amplitude or frequency) provoked by an auditory and a nociceptive standardized stimulation. we evaluated the predictive values of persistent lack eeg reactivity and other indicators regarding their respective ability to predict a favorable or unfavorable outcome. recovery of a level or on the cerebral performance category (cpc) scale at discharge was considered as a favorable outcome, as opposed to recovery of a cpc level - (unfavorable outcome). we included patients who were mostly male ( %), with median age of years. ca occurred in a public place in % of cases, and it was witnessed in % of cases. bystander cpr was initiated in % patients and the initial cardiac rhythm was shockable in % patients. median time to eeg was days ( - ) and % of patients were still sedated during the examination. a favorable neurologic outcome was observed in patients ( %). an eeg reactivity was present in patients ( %) with favorable outcome and in patients ( %) with unfavorable outcome. the positive predictive value (ppv) of a persistent eeg reactivity for prediction of favorable outcome was % . by contrast, the ppv of lost eeg reactivity for prediction of unfavorable outcome was % (ic % - ) with a false positive rate (frp) of . % ( . - . ). eeg electroencephalogram, ssep short-latency somatosensory evoked potentials, ppv positive predictive value, npv negative predictive value, fpr false positive rate in this population of post-cardiac arrest patients, the presence of eeg reactivity was poorly predictive of a favorable neurologic outcome. the absence of reactivity was highly predictive of unfavorable outcome. in combination with other indicators, searching for eeg reactivity may have important implications in the neuroprognostication process. conclusion: this subgroup analyses of a randomized controlled trial, found no survival benefit when comparing crystalloids to colloids in critically ill surgical patients. introduction: goal of a fluid challenge (fc) is in fine to increase the stroke volume (sv) or the cardiac index (ci) when an episode of hypovolemia or a preload dependence status are suspected. fc is one of the most common practices in icus, however, the way to assess the response to fc is not standardized. the present study aimed to evaluate whether the trans-thoracic echocardiographic (tte) assessment of the response to fc immediately at the end of the infusion or delayed min later could affect the results of the fc. patients and methods: prospective, observational, multicentre study including all icu patients in septic shock requiring a fc. were excluded patients with-arrhythmias, poor echogenicity and severe mitral or aortic regurgitation. fc was performed administering ml of crystalloids over min. fluid responsiveness was defined as a > % increase in stroke volume (sv). the following echocardiographic parameters were recorded-e wave, a wave, e a ratio, velocity-time integral (vti), ea wave and sa wave. map, hr and tte variables were collected at baseline (t ), at the end of fluid challenge (t ) and (t ) and min (t ) after the end of fluid challenge. quantitative data are expressed as mean and standard deviation (sd) or median and interquartile (iqr), according to their distribution. qualitative data are expressed as absolute number and frequency (%). results: from may th to january th , a total of patients were enrolled in french icus (mean age- ± years, median igs ii- , median sofa score- [ ] [ ] [ ] [ ] [ ] ). among the ( %) patients responders to fc at t , patients were transient responders (tr), i.e. became non-responders at t ( %, % ci = [ - ]) and ( %, % ci = [ - ])) patients were persistent responders (pr), i.e. remained responders at t . among the non-responders (nr) at t , became responders at t , ( %, % ci = [ . - . ] ). in the subgroup analysis, no statistical difference in haemodynamic and echocardiographic parameters was found between non-responders, transient responders and persistent responders (fig. ) . conclusion: the present study shows that, after a % vti increase at the end of the fc, vti returns to baseline at min in half of the responders. blood volume status (normo or hypovolemia) before initiating the fluid infusion could explain the transient or persistent response to fc observed in septic patients. mottling score is a strong predictor of day- mortality in sepsis patients independently of catecholamine dosing and other tissue hypoperfusion parameters dumas guillaume , joffre jérémie , hariri geoffroy , bigé naike , baudel introduction: sepsis is a frequent critical condition. mottling score, an hypoperfusion parameter, is well correlated with outcome. however, uncertainties persist regarding its value not only as a marker of patient severity but also as an independent predictor of mortality and treatment efficacy. we performed a post hoc analysis of four published prospective studies including sepsis patients with or without shock. we analyzed the relationship between the mottling score (from to ) and day- mortality according to other prognosis covariates such as catecholamine dosing, urine output and plasma lactate levels. first, factors associated with outcome were determined by multivariate analysis. second, mottling score-by-covariate interaction was studied to better understand its effect on mortality. finally, effect of mottling score variation at different time point (h -h -h -h ) was assessed. whereas ecmo was successfully weaned in ( %) patients. proportion of perfused vessel (ppv), perfused vessel density (pvd), micro flow index (mfi) and heterogeneity index (hi) were severely impaired before ecmo. re-establishing high and stable peripheral blood flow with va-ecmo led to a rapid decrease in heart rate and vasoactive inotropic support and significantly improved all microcirculation parameters within h. total vessel density and pvd, measured before and after ecmo initiation, were better in patients successfully weaned from ecmo (p < . ) (fig. ) . conclusion: cardiovascular support with ecmo-va rapidly improved macro and microcirculation in refractory cardiogenic shock patients. total vessel density and perfused vessel density were significantly better in survivors h after ecmo initiation and might therefore help to predict outcomes. further studies are now needed to better define the utility of this technology in larger groups of va-ecmo patients. introduction: thyroid storm is a rare but life-threatening disease related to thyrotoxicosis. it can lead to multiple organ failure including cardiovascular disorders or neurological impairment. to date, data on this disease in icu patients are scarce and limited to case reports. we therefore aimed to describe clinical presentation, outcomes and management of thyroid storm in icu patients. patients and methods: local diagnoses coding database (from january to july ) from french icu were interrogated for main and secondary diagnoses codes including thyrotoxicosis based on the international classification of disease th revision. thereafter two investigators reviewed all the medical records selected. inclusion criteria were thyroid storm based on the diagnostic criteria of the japan thyroid association (t. satoh, endocrine journal ). it combines thyrotoxicosis with elevated levels of free triiodothyronine (ft ) or free thyroxine (ft ) with at least two of the following symptoms-central nervous system manifestation, fever, tachycardia > bpm, congestive heart failure, or total bilirubin level more than micromol/l. clinical presentation, therapy used, and outcome were recorded. results: sixty-two patients (median age years (interquartile range - ) + saps ii ( - ) were included. thyroid storm was the first manifestation of thyrotoxicosis in ( %) patients. graves' disease ( %), amiodarone induced thyroiditis ( %), autoimmune thyroiditis ( %), and toxic multinodular goitre ( %) were the main causes of hyperthyroidism. amiodarone, thyroid hormone toxicity, antithyroid drugs withdrawal or infectious trigger were identified in ( %) patients. organ support including mechanical ventilation, catecholamine infusion, renal replacement therapy and veno-arterial ecmo were used in , , , and patients, respectively. main thyroid storm treatments included antithyroid drugs ( %), betablockers ( %), corticosteroids ( %), and plasmapheresis ( %). lastly, icumortality was %, with multiple organ failure responsible of death in all patients. although its incidence appears low, icu physicians should be aware of the multiple clinical features of thyroid storm. our preliminary data reported various specific therapeutic management of this potentially fatal disease. prompt initiation of targeted therapies is required for atypical hemolytic uremic syndrome (ahus) and thrombotic thrombocytopenic purpura (ttp), but no specific therapy is consensual for shiga toxinassociated hemolytic uremic syndrome (stec-hus). thus, rapid differentiation of stec-hus is mandatory to tailor the initial treatment. furthermore, apart from large outbreaks, characteristic features of this syndrome in adults have not been described. in this study, we retrospectively compared the characteristics of stec-hus, ahus and ttp patients at admission in two expert icus. patient were included if they presented with the triad of mechanical hemolytic anemia, thrombocytopenia and organ damage, and tmas were classified using international criteria. other causes than stec-hus, ahus and ttp were excluded. results: amongst tmas admitted between september and january , stec-hus, ahus and ttp were included. stec-hus patients were older ( ) than ahus ( , p = . ) and ttp patients ( , p < . ). they presented with more frequent digestive symptoms ( versus and % for ahus and ttp, p = . and < . ), but bloody diarrhea was rare ( %) and non-statistically different from other tmas. confusion was more frequent in stec-hus ( %) than ahus patients ( %, p = . ). biologically, stec-hus patients displayed elevated fibrinogen levels ( . vs . and . for a hus and ttp, both p < . ) and severe renal failure. forty-two percent required renal replacement therapy and % were treated with plasma exchange before the distinction from other tmas could be made. only ( %) stec-hus patient died in the icu (fig. ) . conclusion: characteristics supposed to identify stec-hus are largely shared with other tmas. in particular, the differential diagnosis between ahus and stec-hus appears to be more difficult than the stereotypical description derived from pediatric studies. severe hyperglycemia in icu patients: a higher mortality rate and a higher incidence of diabetes in a long-term follow-up study . ], p = . ) but not when admitted for coma, sepsis or cardiac arrest. mortality rate was significantly higher in patients with severe hyperglycemia compared to those without, regardless of preexisting diabetes (hnd hd vs. nhnd nhd groups + p < . ). patients with severe hyperglycemia had a higher incidence of type diabetes at ( vs. % + p = . ) and months ( vs. % + p = . ) compared to those who did not. conclusion: severe hyperglycemia occurring in the first days of icu admission was associated with higher mortality rate and an increased risk of diabetes in the following months regardless of preexisting diabetes. introduction: vitamin d deficiency is frequent in northwestern countries and could represent a modifiable risk factor for critically ill patients, in relation with its pleiotropic effects ( ) . some studies reported an association between oh vitamin d ( oh) deficiency, chronic health status and icu-and hospital-related outcomes. however, a large supplementation study have not been found to improve outcome of patients with moderate oh deficiency (< ng ml) ( ) . the aim of the study is to analyze the relationship between the severity of oh deficiency at icu admission, severity of illness and outcomes and ultimately to identify subgroups of patients in whom the likelihood of benefit of supplementation is larger. patients and methods: consecutive patients admitted over a -month period who stayed at least h in a medical surgical -bed icu were included. in these patients, demographic data, charlson comorbidity score, severity scores (saps and sofa) and -oh (chemiluminescence, diasorin) were collected at admission. icu and hospital length of stay (los) and mortality were recorded. correlations were searched between oh and the different scores, and vital outcomes ( - )). hypothyroidism was unknown before icu admission in % patients. median sofa score at icu admission was ( - ). myxedema coma, circulatory failure, respiratory failure, and severe hypothermia were respectively the main admission reason in , , , and % patients. a precipitating factor such as drugs thyroid toxicity, thyroid hormone withdrawal or infection was found out in only ( %) patients. main causes of hypothyroidism were thyroiditis and thyroidectomy. thirtytwo ( %) patients had alteration of consciousness with a median glasgow score at ( - ). in addition, median heart rate at icu admission was ( - ) bpm while hypothermia < °c was noted in ( %) patients. median tsh level at admission was ( - ) mui l, t and t levels respectively ( - . ) pmol l and ( - . ) pmol l. rhabdomyolysis was frequent with median cpk level ( - ) ui l. organ support including mechanical ventilation, catecholamine infusion and, renal replacement therapy were respectively used in , , and % patients. lastly, % patients received oral levothyroxine whereas the intravenous form was used in others. overall icumortality was %. our preliminary data showed that severe manifestations of hypothyroidism leading to icu admission represent de novo hypothyroidism in two-thirds of patients, leading to a high mortality. introduction: when it comes to infections of the central nervous system (cns), the greatest challenge in the emergency department (ed) is to identify patients that have a rare life-threatening diagnosis. alone or in combination, fever, headache, altered mental status encompass a broad differential diagnosis. antibiotics or antiviral therapy should be given as soon as possible, ideally after both blood and cerebrospinal fluid (csf) have been obtained. early treatment is associated with a lower mortality. patients and methods: we present here, a four-year ( - ) retrospective and monocentric study. during the period of the study, we included all adult patients with the diagnosis of cns infection (positive csf culture). we collected and analyzed all clinical, biological, imaging, treatments and evolution datas during the stay. a total of patients with cns infection have been included for statistical analysis. we analyzed a second group (n = ) with suspected cns infection (negative csf) as a control group. results: in the study population, mean age was ± . years old and the sex-ratio was . . there were no difference between the two groups in terms of clinical signs except for more altered mental status in the control group (p = . ). all patients of the study (n = ) benefited of lumbar puncture (lp) in the ed with an average time of ± min after admission. this delay was the same between the two groups (p = . ) but was significantly higher in the encephalitis subgroup (n = , p = . ). patients who had imaging (ct or mri) during the ed stay had more likely a delay in lp realization ( vs min, p = . ). patients where the cns infection diagnosis was firstly evoke by the triage nurse had lp more quickly (p = . ). the median door to-antibiotic-time was min with no difference between the two groups of the study (p = . ). % of all patients were hospitalized for an average length of stay of . ± . days and % of them were admitted in the icu. the inhospital mortality was % in the study population. introduction: there are numerous causes of acute exacerbations of copd (aecopd), the most common of which are bronchial and or pulmonary infections. viral etiologies may account for % of aecopd, but this rate is likely underestimated because of the limited performance of the conventional diagnostic tests. multiplex molecular diagnostic tests may identify several pathogens including viruses and bacteria, from a single respiratory tract sample, with high sensitivity. using these tests, respiratory viruses are identified in to % of cases, according to the series. the objective of this work was to describe the microbial epidemiology, the management and the outcome of patients admitted to the intensive care unit (icu) with moderate to severe aecopd, in the era of multiplex testing. a prospective non interventional multicenter study conducted in two university-teaching hospitals. in addition to the usual samplings, a nasopharyngeal swab was performed for multiplex polymerase chain reaction (pcr), using respiratory panels fil-marray biomérieux ( viruses and bacteria) or eplex automaton ( viruses and bacteria) depending on the center. the preliminary results involve the patients ( males + years ( - )) included in tenon hospital over a -month period. the mean fev was % ( - ) median % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . drug therapies included anticholinergics (n = + %) and beta- -mimetics (n = + %), inhaled (n = + %) or oral (n = + %) steroids, and azithromycin (n = + %). a respiratory virus was identified in patients ( %), alone or in combination with a bacterium (n = ). a bacterial pathogen was identified alone times ( %). therapeutic interventions did not differ depending on whether a virus was detected or not-exposure to antibiotics ( ± . vs. . ± d + p = . ), administration of oseltamivir ( / vs. / + p = . ), steroids ( / vs. / + p = . ) and mechanical ventilation ( / vs. / + p = . ). the icu length of stay ( . ± . vs. . ± . d + p = . ) was similar. the icu and d-mortality rates were . and . %, respectively. conclusion: respiratory viruses are frequently involved in moderate to severe aecopd. the respiratory multiplex pcr should be performed in this setting and the results should be taken into account to more adequately use the anti-microbial treatments. introduction: prophylactic non-invasive ventilation (niv) is a well established method for prevention of post-extubation acute respiratory failure in hypercapnic patients. however, its role in the postextubation period, in traumatic brain injury patients, is uncertain. especially, because of effects of the brain injury, on respiration and airway control. we perform a study to assess the impact of prophylactic niv after extubation among patients with severe traumatic brain injury. patients and methods: over a period of year, adult patients with isolated severe traumatic brain injury, who were under invasive mechanical ventilation for more than h were eligible for inclusion in the study. they were randomized, after decision of extubation, to receive conventional therapy or conventional therapy associated with niv. conventional therapy consisted of oxygen delivery by facial mask, semi-recumbent position, mucus suctioning and nebulization therapy. the main objective of the study is to assess the impact on reintubation rate. extubation succes was defined by the absence of need for reintubation within the days. the secondary objective is to evaluate the effect on icu length of stay after extubation. the clinical benefit of non-invasive ventilation (niv) in patients with acute hypoxemic respiratory failure (arf) is being called into question. indeed, in a multicenter randomized trial recently conducted in hypoxemic arf patients (pa fi < ), intubation rate in the niv group was % and intensive care unit (icu) mortality rate was %, numbers higher than in the standard-oxygen group ( ) . an excessive tidal volume under niv is a hypothesis to explain these bad outcomes ( ) . our experience does not seem to support these data. therefore we wanted to-investigate the rate of niv success in hypoxemic arf and global in-icu mortality. estimate the average expired tidal volume and identify predictive factors of niv failure. conclusion: though limited by its design, our study seems to show a similar efficacy of niv following ue as compared to planned extubation, with a safety concern for rescue niv and a potential interest for "prophylactic" niv. further data is warranted. which is yet operator dependent and time-consuming, or by invasive methods including esophageal pressure or diaphragmatic electromyogram measurements. the main purpose of this study was to assess the relevance of curvex as a noninvasive diagnostic and classification tool for asynchronism management. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct ) that aims to record consecutive icu patients, over -years. all consecutive patients were recorded for a -hours period during -h following icu admission. all measurements were recorded with the patient laying supine, with a ° bed angulation. raw ventilatory pressure and flow curves were transferred to a centralized server using a dedicated network. the physician in charge of the study was informed of the online analysis on a routine basis. physiological recordings were associated with metadata collection. asynchronisms detection is based on a non-parametric hypothesis testing (random distortion testing), that requires no prior information on the signal distribution. beside asynchrony index monitoring (ai), five asynchronism's types were qualified-ineffective efforts (ie), short cycles (sc), multiple cycles (mc), prolonged inspiration (pi) and premature cycling (pc introduction: international guidelines recommend ultrasound (us) guidance for central venous catheter (cvc) insertion. however, evidence is lacking for several aspects of guidance such as probe shape or whether the needle has to be in plane (ip) or out-of-plane (oop). we assessed these issues in a randomized trial. success at first pass, number of attempts (needle passes), success, times between skin contact and needle skin penetration and between needle skin penetration and liquid back flow in the syringe were recorded. qualitative and quantitative values are expressed as number (percentage), and median (range), and were compared using the wilcoxon matched pairs test and the fisher exact test, respectively. results: for ijv puncture, first attempt success rate was more than % and was neither influenced by probe shape nor approach (table ) . conversely for rav puncture, using lp with ip approach was more frequently successful at first attempt ( vs %, p = . ). time elapsed between needle skin penetration and liquid back flow was shorter for rav puncture using ip approach ( s vs s, p = . ). time elapsed between probe appliance on skin and liquid back flow was significantly shorter with the linear probe for ijv whatever the approach and for rav using ip approach. rav puncture was more frequently impossible with mcp ( vs %, p = . ). arterial puncture occurred more frequently with mcp ( vs %, p = . ). lp use and ip approach were associated with more free event puncture ( ± ) . minimal ani, reflecting intense stress was . (± . ). objective and subjective stress of each team leader is shown in fig. . there was a significant negative linear correlation between minimal ani and maximal hr (rho = − . , p = . ). there was no significant correlation between self-reported stress vas (neither pre hfs or maximal stress) and minimal ani. conclusion: hrv monitoring is a feasible method to evaluate continuous physiological stress for team leaders in highly stressful simulationteaching. upgrading signal connection by bluetooth . or wi-fi could improve the method. focusing on specific stressful time points might improve stress assessment and its correlation with performance. introduction: simulation training has become available in health sciences faculties and proposed in many specialties. intensive care is one of the fields of development of simulation based training. the aim of the present study was to report the experience of the faculty of medicine of monastir simulation center in training medical students and residents in intensive care and to compare their respective perceptions. this was a descriptive study including students ( th year of the medical curriculum) and residents who received training during the last academic year ( ) ( ) , in the simulation center during their icu traineeship. simulation training was based on high-fidelity mannequins for students and seminars with high fidelity and procedural simulation training for residents. three sessions per group were organized for students and a total of five sessions for residents. we collected participant characteristics and used likert scale (from to ) to assess participant satisfaction, simulation fidelity, impact on clinical practice, stress level and instructor behaviors. chi test was used to compare students' and residents' perception of the simulation based-training. results: during the study period students (of the students' whole promotion) and residents actively participated at least in one of the simulation-based training sessions. median students' and residents' ages were respectively years ( - ) and years ( introduction: hospitals are encouraged to edit local antibiotic therapy guidelines. antibiogarde ® is an electronic antibiotic prescription referential developed by a multidisciplinary team of french physicians, regularly updated, and locally customizable, which has been purchased by more than french hospitals. we compared adequacy fig. team leader's objective (heart rate and ani) and subjective stress (declared vas stress) of initial antibiotic prescription by icu clinicians, antibiogarde ® proposal and national or international guidelines. patients and methods: between january and june , initial antibiotic prescriptions in an icu were retrospectively analyzed when microbiologically documented. antibiogarde ® and guidelines proposals were simulated, considering data available at the time of initial prescription. adequacy was defined when all bacteria responsible for infection were sensitive to at least one prescribed proposed antibiotic. national guidelines were used when published after . otherwise, most recent international guidelines were used. results: initial prescriptions were analyzed ( monotherapy) in patients (median age y, median saps ii , median sofa on prescription , icu mortality %, % immunocompromised). main sources of infection were lung (n = ) and intra-abdominal (n = ). leading isolated bacteria were enterobacteriaceae (n = , antibiotic resistance in ), streptococci (n = ), non-fermenting gram negative bacilli (n = , antibiotic resistance in ) and staphylococci (n = , resistance to methicillin in ). in the clinical settings analyzed, there was a proposal by antiogarde ® in ( %) and a guideline available in ( %) (p = . introduction: intubation is plagued with a high morbimortality, especially in emergency situations. it is now acknowledged that a seated position allows for optimized preoxygenation ( ) . however, there is no guideline concerning the patient's position for intubation. the patient is most often laid in a supine position, leading to a higher risk of aspiration ( ) . face-to-face intubation in sitting position (ftfi) would allow for an easier intubation and a lower morbidity. we focused on learning the ftfi technique using the macintosh laryngoscope and the airtraq videolaryngoscope in simulated difficult intubation situation and comparing the performance of the ftfi with the classic technique. the participants would intubate a high-fidelity manikin (simman g, leardal, norway) configured with a tongue edema (cormack b- ). for each trial, time to intubate (tti), success and complication rate, intubation difficulty and glottis exposure were noted. in classic position, three trials were performed with the airtraq followed by the laryngoscope in order to obtain baseline parameters. in ftfi, at least intubations were performed by each participant for each device. the utilization order was randomized. results: thirty physicians, with an experience of at least intubations each, were included. figure shows the learning curves of the ftfi based on the evolution of the tti measured for the airtraq and the laryngoscope. in classic position, the mean tti with the airtraq was . ± . s versus . ± . s with the laryngoscope (p = ns). in ftfi, once the technique mastered, the tti was ± . s with the airtraq versus . ± . s with the laryngoscope (p < . ). success rate, tti, complication rate, intubation difficulty and glottis exposure were better using ftfi versus classic intubation (p < . ). these parameters were even better with the airtraq than with the laryngoscope (p < . ). the learning profile of ftfi is different between the airtraq and the laryngoscope. it could be due to the participants' lesser familiarity with the airtraq. the better performances in ftfi could be due to better ergonomics allowing easier glottis exposure and learning ( ) . conclusion: face-to-face intubation in sitting position is easy to learn. it provides better performances and fewer complications than the classic intubation technique which might result in a lower morbidity. the airtraq provides even better results than macintosh laryngoscope. all participants recommend their colleagues to be trained in face-toface intubation. among non-invasive respiratory support, niv with bilevel pressure was the most frequent (n = , %) before cpap (n = , %) and high flow oxygen (n = , %). the proportion of patients on niv was up to % in the centres hosting more acs patients. conclusion: despite the absence of evidence from randomized controlled trials niv is nowadays commonly used in picu and hdu for scd patients with acs, especially in centres taking in charge a high number of scd patients. future physiological studies and randomized controlled trials might help to choose between the different ventilatory support options for acs. in transfused patients, the pre-transfusion hemoglobin was . ( . - . ) g dl in moderate pards and . ( . - . ) g dl in severe pards. the evolution of hemoglobin, osi, scvo and lactate after the transfusion is reported in the table . in our picu, a relatively restrictive policy of rbc transfusion was observed even in patients with severe pards. decision to transfuse seemed associated with the general severity status of the patient and with the hemoglobin level. further studies are needed to explore the generalizability of these findings, and to investigate the impact of transfusion on oxygen transport consumption balance in pediatric acute respiratory distress. introduction: pharmacokinetic parameters are altered in critically ill patients. for instance, in adult patients, it has been well demonstrated that augmented renal clearance results in subtherapeutic antibiotic concentrations. our objectives were to build a pediatric population pharmacokinetic model for piperacillin, in order to optimize individual dosing regimen. patients and methods: all children admitted in pediatric intensive care unit, aged less than years, weighing more than . kg, and receiving intermittent piperacillin infusions were included. piperacillin was quantified by high performance liquid chromatography. pharmacokinetics were described using the non-linear mixed effect modelling software monolix. monte carlo simulations were used to optimize dosing regimen, in order to maintain plasma concentration above the minimum inhibitory concentration ( mg l − for pseudomonas aeruginosa) throughout the dosing interval ( % ft > mic). results: we included children with a median (range) post natal age of . ( . - . ) months, median (range) body weight of . ( . - ) kg, median (range) pelod- score of ( - ) and median (range) estimated creatinine clearance of ( - ) ml.min - .m - . a one compartment model with first-order elimination adequately described the data. median (range) values for piperacillin clearance and volume of distribution were respectively ( . - ) l h − and . ( . - . ) l. body weight (allometric relationship), estimated creatinine clearance and pelod- severity score were the covariates explaining the estimated between subject variability. a third of the cohort attained the target, according to our dosing regimen and to the european guidelines. to reach the target and according to the simulated dosing regimens, children with acute kidney injury should receive intermittent infusion every h, administered on min. those with augmented renal clearance should receive a continuous infusion. to reach the target, standard intermittent piperacillin dosing regimen in critically ill children is not appropriate. in addition to body weight, dosing regimens should take into account the creatinine clearance. continuous infusion is adequate for children with augmented renal clearance. piperacillin individualized dosing regimens and therapeutic drug monitoring are mandatory in pediatric intensive care unit. introduction: all data support the need for early recognition, evaluation of pain in the nicu. multiparametric analysis including physiological parameters could be useful to have a more objective evaluation of pain in the nicu compared to scales built on external-evaluation. the newborn infant parasympathetic evaluation (nipe ® ) was developed to assess pain in newborns and infant, from preterm to the age of years. patients and methods: we conducted a monocentric, prospective study to compare the instantaneous nipe ® index value (nipei ® ) to the dan scale during acute procedural pain (picc line insertion) in preterm infants (under gw). the operators and the nurse were blinded to the continuous recording of nipei ® during the entire procedure. dan scale was assessed every min by a third person, trained to this scale and blinded to nipei ® . a direct correlation assessment between the dan scale and the nipei ® was performed by calculating the pearson's linear correlation coefficient. the differences between the nipei ® of non-painful (dan < ) and painful (dan ≥ ) infants were estimated by the wilcoxon-mann-whitney test. the usefulness of nipei ® as a new tool for pain assessment in neonates was estimated by the corresponding roc curve. our study was approved by our local ethic institutional review board. results: thirty-five preterm infants were included, nipei ® data were incomplete in infants. fifty percent of newborns were born before gw, and % had non-invasive respiratory support (continuous positive airway pressure cpap). at the time of the procedure, newborns had a median post-natal age of days and a median weight of grams. there was a moderate correlation between the nipei ® index and the dan scores (r = . + p < . ). the median nipei ® index was for non-painful events vs. for painful events, p < . . the area under the roc curve was . . for a threshold of nipei ® < , the sensitivity was . %, the specificity was %. positive likelihood ratio was . and the negative likelihood ratio was . ( fig. ) . we showed a correlation between the dan scale and the nipei ® index for pain assessment in preterm infants. the nipe ® monitor could be a useful and non-invasive tool for pain assessment in neonates. further studies are needed to confirm our results and to define more precisely the place of such monitors for pain evaluation in daily clinical practice in the nicu. introduction: the aim was to identify factors associated with the occurrence of acute pituitary hormone dysfunction in children with moderate to severe tbi and to describe the impact of this dysfunction on the stability of the children. patients and methods: prospective bicenter study including all children aged between month to years, admitted to picu for a moderate-severe tbi and with an expected stay > days. setting-pediatric intensive care units of grenoble and lyon, from to . endocrine explorations at the second morning following admission and h before discharge were performed-cortisol h cycle with free cortisol and acth dosages every h (or h if no central line) + free h urinary cortisol + tsh and t l, h urinary lh and fsh, blood level of testosterone or estradiol for children aged > years, and igf . patients were classified as having cortisol insufficiency if all the cortisol dosages were < nmol l and all acth were < pg l. tsh deficiency was defined as t l < . pmol l and tsh < . mui l. gonadotropin defciency was defined as urinary lh < . ui h and urinary fsh < . ui h for males + urinary lh < . ui h and urinary fsh < . ui h in female. patients with deficiency (acth and any deficiency) were compared to those without deficiency in terms of hemodynamic instability, respiratory instability, neurological and infectious complications for continuous variables means and % confidence interval were calculated and compared by t student test. chi- test was used to compare proportions. results: among the patients evaluated, had acth deficiency, and had at least one acute pituitary dysfunction. comparison of patients who presented acth deficiency with those who were not deficient found no differences in terms of patients characteristics, cause of tbi, level of severity and level of injury. paitents with acth deficiency required more frequently fluid bolus at day ( vs %, p = . ). all the markers of severity were higher and the need of vasoactive drugs were more frequent but the differences were not statistically significant. table shows comparison between patients with at least one pituitary hormone deficiency to those without deficiency. the same result was found. glycemia levels were lower in the group with deficiency. conclusion: we didn't find any predictive factors of pituitary hormone deficiency in children with moderate-severe tbi justifying a systematic screening of those patients. introduction: most intensive care unit (icu) patients cannot make decisions themselves. familiy members are actively involved in the care process as surrogate decision-makers and judges of care quality. however, family satisfaction with care is complex and is not clearly defined. the aim of this study is to evaluate the different procedures (reception book and staff education for aid and relationship) used in a new icu to improve the family care. patients and methods: we included in our study patients who had spent more than h in our department. a questionnairy, adapted to our population, was performed by our staff and validated by the hygiene and quality care departement. we proceded by phone calls, months after the inauguration of our icu. results: sixty-five questionnaires were included (fig. ). the average of age was ± with a sex ratio of . the average of the simplified acute physiology score (sapsii) was ± . the median stay was days [ - ] with a total mortality rate of %. mostly, we interrogated first-degree parents (n = ). only three families recieved reception book at admission. visit in patient room was autorised only for % (n = ) of family members. only four persons said they were disturbed in visit hours for architectural reasons (tight space). disponibility was found excellent in % (n = ) of cases for medical staff, % (n = ) for paramedicals. informations provided by physicians were clear in . % (n = ) of cases. fifteen of the family members ( %) asked psychology support. patients were followed up via phone calls during year after discharge. characteristics on admission and outcomes after discharge were analyzed stratified by ventilation modality niv vs imv. the overall survival was analyzed on the basis of the kaplan-meier curves. results: during the predetermined period of data collection, the follow-up involved patients. patients were treated by niv (group ) and patients needed imv (group ). there was no difference between the groups in age (p = . ), severity of copd (p = . ), physiological reserve at discharge (p = . ) and icu readmission (p = ). short term outcomes were not different between the groups- -month readmission ( . vs % respectively in niv and imv, p = . ) and -month mortality ( introduction: post-intensive care syndrome (pics) has been recently described as a combination of physical, cognitive and mental impairments appearing during a stay in an intensive care unit (icu). the prevention and detection of pics require the participation of each category of healthcare workers. however, the level of knowledge is unknown. we sought to assess the awareness among our icu staff in preparation for a follow-up consultation. the study used a short multiple-choice survey filled on a voluntary basis. all members of the staff were asked to fill the questionnaire over a one-week period. the assessment was composed by seven structured questions which aimed measure basic knowledge of post-intensive care syndrome and general strategies to diagnose that syndrome and the tests used. results: fifth five workers ( % of the staff ) of the department of intensive care answered the questionnaires ( % nurses, % physiotherapists, % physicians). the estimated ranges of prevalence of psychological problems were very low ( - %) for . %, low ( introduction: drafting a death certificate (dc) is a procedure considered as a part of doctor's daily practice, especially in emergency and intensive care departments. this certificate represents a civil, social, epidemiological and medico-legal act. it can engage the liability of the certifying doctor. the objectives of our study were to examine the content of dc drafted in emergency and intensive care departments, assess the quality of writing, and analyze drafting errors. patients and methods: a prospective study extended over a period of months from january to december , including all dc emanating from emergency and intensive care departments and received in the forensic department of habib bourguiba hospital in sfax. results: during the study period, dc meeting the inclusion criteria were collected. although confidential, the medical part of the dc was sealed by the doctor in onlyone third of cases. in the administrative section, nine socio-demographic parameters were studied. in % of the cases, less than four of the nine criteria were found. in the section concerning the certifying doctor data, parameters were screened. . % of the certifying doctors met at least six criteria. the most frequently missing parameter in this section was the identity of the person to whom the certificate was issued. the identity of the doctor was not mentioned in % of the cases. forensic data ( items) was complete in over three quarters of the certificates. nevertheless, in . % of cases, the medicolegal obstacle to burial box was left empty ( . %) or not ticked even if judicial investigation was required ( . %). the section on causes of death was the source of almost all of the drafting errors. we have classified these errors into six major ones, according the classifications reported in the literature. the percentage of certificate without faults was %. the most common major error was insufficient cause of death found in . % of cases followed by incorrect sequence of causes of death ( . %), medicolegal obstacle to burial not ticked although required ( . %), several causes of death mentioned simultaneously ( . %), unacceptable cause of death ( . %) and mechanism of death mentioned instead of the cause of death ( . %). our study showed that the quality of drafting of dc suffered from several insufficiencies, which encourages us to provide more effort in training doctors and to review the current official model of dc. introduction: septic shock is defined as a sepsis with hyperlactaemia greater than mm after correction of hypovolemia requiring vasopressors to maintain mbp > mmhg [ ] . it can be observed in pre-hospital emergency medicine (phem). the use of a reliable portable device for measuring lactate in phem would allow a better evaluation of septic patient facilitating their orientation towards intensive care unit (icu) or emergency department (ed). this portable delocalized biology device must be validated against the laboratory reference method (nfen iso ) [ ] . the aim of this study was to clarify the validity of a delocalized measure of lactatemia. we performed a prospective study including patients admitted into icu for septic shock (cpp number - - sc). lactate was measured in parallel on samples-one capillary with the portable device (lactate statstrip xpress, nova biomedical) and the other venous on a centrifuge tube for plasma analysis (architect c abbott diagnostics). we evaluated the analytical performance (coefficients of variation (cv) for repeatability and reproducibility evaluated at levels of quality control (qc)- . and . mm) and then the concordance between lactate levels measured by the devices and lactate levels measured by laboratory analyzer. results: at the qc concentrations tested, the cvs were in agreement with the limits set by the french society of clinical biology-cv < % for repeatability and < % for reproducibility. an excellent correlation was observed between the measurements-correlation coefficient r = . , slope = . and ordered at the origin = . . the latter suggested a low positive bias of the device not confirmed by bland-altmann graph analysis and graph of the differences. we verified the analytical performance of the device and showed an excellent correlation with the laboratory measurement. the delocalized measure can be used in phem in patients with suspected sepsis syndrome. this measure should allow a more accurate and early assessment of their severity in order to improve triage and hospital orientation between ed and icu. there is an association between mortality at d and hyperoxia in patients admitted in icu for refractory ohca requiring ecpr. these data underline the potential toxicity of high dose of oxygen and suggest that control of oxygen administration in such patients is an important part of the treatment. a value of pao between and mmhg after starting ecpr seems to be a target during treatment of ohca treated by ecpr. introduction: sepsis has been defined as a dysregulated host response to infection leading to life-threatening organ dysfunction (singer m et al., jama ) . a qsofa score relying on simple clinical criteria (respiratory rate, mental status and systolic blood pressure) has been proposed to better identify septic patients with associated higher mortality outside the intensive care unit (seymour cw et al., jama ) . the study aim was to evaluate the ability of qsofa to predict the development of organ failure and increased -day mortality in patients admitted for suspected sepsis in the emergency department (ed). patients and methods: prospective study conducted over a period of months comparing the prevalence of organ failure and -day mortality according to the value of qsofa at admission to the ed between group a (qsofa > = ) and group b (qsofa < ). as part of routine care, an electronic sepsis form was specifically created to identify prospectively and exhaustively all eligible patients on-line. for the purpose of the study, sepsis diagnosis was independently validated off-line by an adjudication committee which included three physicians who reviewed clinical, biological and microbiological data. for each patient, demographic data, source of infection, qsofa and sofa score, biological data and -day mortality were recorded. seventy-six patients of group a ( %) were hospitalized, of whom were admitted to the intensive care unit ( . %), and -day mortality reached . %. in group b, only patients developed an organ failure ( . %) and -day mortality was . % (table ) . the present study confirmed that the qsofa score is a reliable and practical tool to predict the development of organ failure and higher -day mortality in patients with suspected sepsis in the ed. limits of ct scan criteria and intravascular contrast extravasation to define pelvic angioembolization need: a specific assessment on the risk of false- introduction: opening of the mitochondrial permeability transition pore (ptp), triggered by cyclophilin-d (cypd) binding under stress conditions, plays a key role in ischemia-reperfusion injury. we sought to determine, using transgenic mice, whether cypd deletion (cypd −) would improve resuscitability and survival after experimental cardiac arrest (ca). additionally, we compared the protective effects of cypd deficiency with that of targeted temperature management (ttm). patients and methods: anesthetized mice underwent a min asphyxial ca followed by resuscitation (cardiac massage, resumption of ventilation, epinephrine). four groups of animals were studied-sham, control (ctrl), cypd-ca using mice lacking cypd (knockout mice), and ttm-ca with fast hypothermia induced by external cooling at reperfusion ( °c for h). two hours after ca, the following measurements were carried out (n = - group)-echocardiography, cellular damage markers (including s b protein and troponin ic) and mptp opening in mitochondria isolated from brain and heart. additional mice (n = - group) were included in the same groups for survival follow-up ( h and days). results: characteristics of ca were similar among groups. rate of restoration of spontaneous circulation (rosc) was significantly higher in cypd-and ttm groups compared to controls (p < . ). time to rosc was shorter in cypd-versus ttm and ctrl (p < . ). genetic loss of cypd and ttm prevented to a similar extent ca-induced myocardial dysfunction, increase in blood levels of both s b protein and troponin ic (p < . versus ctrl). ca resulted in a significant increase in ptp opening only in mitochondria isolated from brain (p < . versus sham). cypd deletion as well as ttm limited ca-induced ptp opening in brain (p < . versus ctrl). short-term survival ( h) was significantly improved in the cypd-and ttm groups when compared to controls (p < . ). however, only therapeutic hypothermia improved survival at day (p < . versus ctrl). in our murine ca model, genetic loss of cypd increased resuscitability and short-term survival but, unlike therapeutic hypothermia, failed to improve -day survival. introduction: early prediction of neurological outcome of post-anoxic comatose patients after cardiac arrest (ca) is challenging. prognosis of comatose patient relies on multimodal testing-clinical examination, electrophysiological testing and structural neuroimaging (mainly diffusion mri). this prognostication is accurate for predicting poor outcome (i.e. death) but not sensitive for identifying patients with good outcome (i.e. consciousness recovery). resting state functional mri (rs-fmri) is a powerful tool for mapping functional connectivity, especially in patients with low collaboration. several studies showed that rs-fmri can differentiate states of consciousness in chronically brain-damaged patients. a recent study also showed that functional neuroimaging can early detect signs of consciousness in patient with acute traumatic brain injury. however, rs-fmri has not been assessed for the early prognostication of post-anoxic comatose patient. we assessed whole-brain function connectivity (fc) of post-anoxic comatose patients early after ca using rs-fmri. nine patients ultimately recovered consciousness (good outcome) while eight died (poor outcome). we estimated fc for each patient following a procedure previously described. we statistically compared whole-brain fc between good and poor outcome group, to assess which brain connections differed between them. then, we trained a machine-learning classifier (a support vector machine, svm) to automatically predict coma outcome (good poor) based on wholebrain fc of comatose patients. finally, we compared this outcome prognostication based on functional mri to those using standard structural diffusion mri. results: good and poor coma outcome groups were similar in terms of demographics, except for time to rosc. good outcome group showed significant increase in whole-brain fc between most cortical brain regions + with the strongest changes occurring within and between occipital and parietal, temporal and frontal regions ( fig. ). using whole-brain fc and a svm classifier to predict coma outcome yielded to an overall prediction accuracy of . %(auc . ). interestingly, automatic outcome prognostication using functional neuroimaging achieved better results that structural neuroimaging methods like dwi (accuracy . %). conclusion: we used rs-fmri to predict coma outcome in a cohort of post-anoxic comatose patients early after ca. we deliberately chose to include only patients with indeterminate prognosis after standard multimodal testing, to assess the contribution of rs-fmri in the early prognostication of coma outcome. we found that automatic prediction based on functional neuroimaging yielded much better results than current dwi methods, notably for identifying patients who recovered consciousness. outcomes of post-anoxic comatose patients early after ca, using rs-fmri in rcts comparing treatment of severe pneumonia that may influence their ability to demonstrate differences between studied drugs. clinical cure was the most frequently used endpoint but its definition was highly variable. these results are not surprising as far as even guidance from regulatory agencies on how to evaluate hap vap treatments differ. the aim of this work was to reach a consensus on the most appropriate endpoint to consider in future clinical trials evaluating the efficacy of antimicrobial treatment for hap vap, using delphi method. patients and methods: twenty-six international experts from intensive care, infectious disease and from the industry were consulted using delphi method (four successive questionnaires) from january to january . more than % of similar answers to a question were necessary to reach a consensus. results: according to % the experts, clinical cure was the most desirable primary outcome among those found in the literature but two other endpoints were highly rated-all-cause mortality and mechanical ventilation (mv)-free days. consequently, % of the panelists agreed to use a composite endpoints and even a hierarchical composite endpoint to combine these items together in which clinical cure and mv-free days would be assessed at day and clinical cure at day after end of therapy. for vap, mortality was considered as the most clinically significant item by % of the experts, followed by mvfree days and finally clinical cure (fig. ) . for hap, a dual composite endpoint that only included all-cause mortality and clinical cure was chosen ( fig. ). among the various elements of clinical cure definition found in the literature, only three were retained by the experts-resolution at end of therapy of signs and symptoms present at enrolment, no further antimicrobial treatment needed and resolution or lack of progression of radiological signs of pneumonia. finally, we found a consensus on the signs and symptoms that should trigger the suspicion of pneumonia-worsening of gaz exchange, purulent tracheal secretions, hypotension and or vasopressor requirements and fever or hypothermia. we provide here two consensual endpoints (for vap and hap) that would help addressing the efficacy of antimicrobial molecules for hap vap treatment in future clinical trials. (table) . sm-vap were matched with control patients. in univariate analysis, risk factors for sm-vap weremale gender, chronic heart failure, respiratory, cardiovascular and coagulation sofa scores two days before vap, median number of antibiotics used, percentage of time with antibiotics before vap, parenteral nutrition, dialysis, catecholamine use and exposure to ureido-carboxypenicillin, ciprofloxacin, tazobactam or imipenem-meropenem during the week before vap (table) . patients with sm-vap were less likely to receive initial adequate therapy ( vs %, or . , p = . ). there was no statistical difference for icu or d mortality. d mortality was higher for sm-vap (table) . in multivariate analysis, exposure to imipenem-meropenem during the week before vap, respiratory and coagulation sofa scores two days before vap were independent risk factors for sm-vap. sapsii: simplified acute physiology score; sofa: sofa (sequential organ failure assessment); sofa resp: sofa respiratory score; sofa coag: sofa coagulation score; sofa cardio: sofa cardiovascular score conclusion: sm-vap represented . % of vap. we observed no differences in patients characteristics between the groups. imipenem-meropenem use during the week before vap was the most important risk factor for sm-vap. the higher risk of inadequate initial therapy with sm-vap had no impact on d mortality but d mortality was significantly higher. introduction: education of undergraduate students is key to improve hand hygiene (hh) behavioral changes amongst doctors [ . ] . our aim was to evaluate personal feedback using ultraviolet (uv) light inspection cabinets in a years program. our hypothesis was that its use for alcohol hand rub (ahr) application on first year would increase complete ahr application on nd year. patients and methods: this was a simple blind randomized trial comparing hh training with personal feedback using uv cabinet to a control group. on first year, students had access to a theoretical formation then were convened by groups for a demonstration of the correct execution of world health organization's (who) procedure [ ] . before hh training, each group underwent a cluster randomization. in the control group, the student hand rubbed under visual supervision and advises of a trainer. in the intervention group after the same visual assessment, completeness of ahr hand application was recorded under uv light and shown to the student. he was given free access to the uv cabinet to repeat the technique, until perfect application complete under uv light. an enhancement with a scenario-based learning was proposed to both groups. on second year, every student were asked to hand rub with the fluorescent ahr. a supervisor blinded to the group of randomization assessed the quality of the hh procedure visually, the completeness of hand application under uv light and compliance with the who's opportunities for hh during the simulation. results: after randomization students were included in the intervention group and in the control group. on second year, the rate of complete application of the ahr under uv was increased in the intervention group as compared with the control group ( % versus . % p < . ) ( fig. ) despite that visual assessment of hh procedures was similar between the two groups. in a logistic regression model including gender, intercurrent hh formation, intercurrent uv cabinet use, surgical unit traineeship and report of regular use of ahr, the hazard ratio for the intervention was . (ic . - . ). the rate of perfect compliance with the hh opportunities in the intervention group was increased ( . % versus . % p < . ) and the effect persisted in the logistic regression. conclusion: uv cabinets for undergraduate students' hh education improve the technique and the compliance with hh opportunities. included in a multifaceted education program, it must be considered a key tool for training. results: among the patients who underwent ecmo support for more than h, the bsi prevalence was . cases per ecmo days and microorganisms associated were most frequently gramnegative bacilli. as for positive ta cultures, microorganisms associated were oropharyngeal germs and gram-negative bacilli. two risk factors were associated with nosocomial bacteria occurrence in ta cultures-prior antibiotics and duration of mechanical ventilation more than days. we demonstrated a link between "positive ta culture" and "positive blood culture" and we showed a protective effect of using an antibioprophylaxis on "positive ta culture" and "global positive cultures" development. introduction: delirium in the icu is often under-diagnosed despite its related burden and impact on patients' morbidity, mortality and prolongation of hospital length of stay. the aim of this study was to assess the medical and paramedical community beliefs and practices regarding delirium in tunisian icus. patients and methods: between august st and / , healthcare professionals working at the icus of university hospitals of monastir and mahdia (tunisia) were asked to participate in the survey by completing a questionnaire anonymously (that specified participants' characteristics (age, gender, function, years of experience in icu) and their knowledge and perception of delirium in icu. the questionnaire consisted in questions of different types: likert style (: widespread scale in psychometric questionnaires in which the respondent expresses his or her degree of agreement or disagreement with an assertion), multiple choice, ranking and yes/no). results: during the study period, respondents out of ( % female, nurses: %), aged between - years in %, responded to the questionnaire. healthcare professionals experience in the icu was < year in . %; - years in . %, and > years in . %. participants asserted that the "most characteristic signs of delirium" were: insomnia ( %); confusion ( %); agitation ( %) and aggressiveness ( %). three-quarters of participants said they did not systematically search for signs of delirium in their patients. % thought that delirium was "an insignificant problem" or that "it was not a problem". only one and three participants respectively, said they attended a conference and read an article about delirium in icu the last year. half of the respondents felt that the most appropriate treatment for a patient with delirium was restraint. nearly one-third of participants thought that delirium was an under-diagnosed entity and only % felt that it was associated with long-term neuropsychological deficits. factors considered to be determinant in the occurrence of delirium were ards, shock, age, mechanical ventilation, postoperative status in , , , and %, respectively. conclusion: most tunisian healthcare professionals consider delirium as a common, underdiagnosed, and serious problem in the icu. yet, few participants actually monitor this condition. the influence of sedation choice on the delirium occurrence in critically ill poisoned patients: a randomized controlled trial khzouri takoua introduction: delirium is a common manifestation of acute brain dysfunction in critically ill patients. it is associated with a healthcare cost increase, and extension of the hospital stay length. the present study aimed to explore influence of patient characteristics and analgesicsedation on delirium incidence and to analyze its risk factors. patients and methods: it is a prospective single blind randomized controlled trial, started on the first july in a -bed toxicological intensive care unit, including all mechanically ventilated patients requiring sedation who were admitted for acute poisoning. they were randomly divided into two groups g et g receiving respectevily propofol-remifentanil and midazolam-remifentanil. delirium assessment scores were judged not adapted to our population and we retained the diagnosis of delirium on arguments inspired from diagnostic and statistical manual of mental disorders fourth edition (dsm-iv). results: until the th september , patients were included, with patients in g and in g . the two groups were comparable in terms of epidemiological characteristics. delirium was developed in patients ( %) (n = in g and n = in g ) with an average duration of ± h with no difference between the groups ( ± h for g - ± h for g , p = . ). compared to those without delirium, no differences were found in the patient characteristics among these two groups with regard to sex, age, psychiatric history and severity of illness (apache ii, igs ii score) and even with regard to hypnotic choice ( vs p = . ). delirium was associated to prolonged duration of mechanical ventilation ( ± h vs ± h, p = . ) and length of icu stay ( . h vs . h, p = . ) without significant differences. delirious patients had more hypotension (p = . ), and received more atropine ( . ). multiple logistic regression analysis identified atropine (or . , %cl . - . , p = . ) as an independent risk factor for delirium. the diagnosis and prevention of icu delirium are subjects of multiple ongoing investigations. we carried out this study to detect the risk factors of delirium in order to prevent it. it is important to note that our results are influenced by the studied population and are only preliminary. we rely on the study pursuit and the sample enlargement to better inform us as well on risk factors as protective. introduction: background: severe alcohol withdrawal syndrome is a common cause of hospital admission. delirium tremens is a potentially fatal complication of alcohol withdrawal. in severe delirium, very large dosages of benzodiazepines can be required despite well described side effects, such as coma and hypoxic cardiac arrest, although there is no recommendations for standardized treatments. objective -the aim of this study was to describe outcomes and risk factors for complications in patients with severe alcohol withdrawal syndrome treated in intensive care unit with continous infusion of benzodiazepine (bzd). we retrospectively reviewed the medical records of all patients hospitalized for alcohol withdrawal syndrome between and . only those who received continous-infusion of bzd, associated with close clinical monitoring and the evaluation of rass and cushman scores, without systematic recourse to mechanical ventilation, were included. results: we studied patients hospitalized in icu for severe alcohol withdrawal syndrome. the mean age (sd) was . ± . years, mean icu admission saps (simplified acute physiology score) ii score was ± . . all of them have received continous infusion of midazolam, with a median maximum perfusion velocity of mg h (interquartile range, ( , )). the median duration of treatement was days (interquartile range, ( , ) ). thirteen patients ( %) developed pneumonia, and or required intubation, and ( %) have had seizures. no cardiac arrest and death was observed. icu length of stay (los) was days ( , ) (median, interquartile range). patients who requiried intubation and or developed pneumonia, received substantially more bzd (median total dose, mg of midazolam vs. mg in the non-complicated group + p < . ), and their icu los was higher (median, days vs. days + p < . ). endotracheal intubation and or development of pneumonia were associated with a higher maximum perfusion velocity of midazolam (> mg h) (or . , ic % ( . - . ), p = . ). previous episodes of delirium tremens before icu admission were associated with higher complications such as mechanical ventilation and or pneumonia (or . , ic % ( . - . ), p = . ). in severe delirium, very large dosages of benzodiazepines can be used without systematic mechanical ventilation with a low incidence of complications. introduction: delirium is frequent in intensive care unit (icu) patients and is associated with increased mortality, increased hospital stay, increased cost and long term cognitive impairment in survivors. numerous pharmacological and non-pharmacological strategies have been investigated for delirium treatment without success. therefore delirium prevention strategies are recommended by current critical care practice guidelines. among the potentially modifiable risk factors for delirium, the impact of daylight exposure on delirium incidence and or duration has not been studied. the objective of this study was to investigate whether daylight exposition would reduce delirium burden in critically ill patients. we conducted a prospective study in a -bed medical intensive care unit (icu) over a -year period (january -january ). all consecutive adult patients receiving invasive mechanical ventilation (mv) for days or more were eligible for the study. patients were assigned to a room with windows allowing daylight exposure ("light" group) or without window ("dark" group), depending on bed availability. delirium was evaluated with the intensive care delirium screening checklist (icdsc) for a maximum period of days. delirium was defined by a icdsc score ≥ for two consecutive days. agitation was defined by a rass > or = + . the primary endpoint was cumulative incidence of delirium. data are presented as median (interquartile range) or number (percentage). results: a total of patients were included (age- [ + ] years, saps - [ + ], sofa score- [ + ], medical admission- %). of them, patients were admitted to a "light" group and to a "dark" group. incidence of known risk factors for delirium was similar in the two groups. delirium occurred in ( %) patients in the "light" group and in ( %) patients in the "dark" group (p = . ). the duration of delirium was [ + ] days. patients in the "light" group received significantly less neuroleptics to treat agitation than patients in the "dark" group ( vs. %, p = . ). this protective association persisted after adjustment for confounders in multivariate analysis (odds ratio = . + [ . + . ] + p = . ). daylight exposure does not impact on delirium burden in icu mechanically ventilated patients. however, daylight exposure is independently associated with a reduced prescription of neuroleptics to treat agitation. introduction: patients with convulsive status epilepticus (cse) frequently require mechanical ventilation (mv), either for general anesthesia in case of refractory generalized cse, or for airway protection. guidelines for the management of refractory generalized cse currently recommend general anesthesia for - h, followed by gradual withdrawal. our objective is to evaluate the incidence of refractory generalized cse among patients who required mv during pre-hospital management of status epilepticus, and to describe the management of general anesthesia in intensive care unit (icu). this ongoing multicenter retrospective observational study is conducted in french icus. all patients admitted in icu under mechanical ventilation between - - and - - with disease-code "status epilepticus" are included. exclusion criteria are-age < years, post anoxic se, acute traumatic brain injury, initiation of mv in icu, transfer from another icu, inclusion in a therapeutic trial on se, non-convulsive se. collected data include reason for mv, antiepileptic treatment, dosage and duration of general anesthesia, mode of eeg monitoring. outcomes are-relapse of se, mv duration, in-icu length of stay and mortality. results: among the medical files reviewed, met the inclusion criteria and were analyzed, and were excluded. a minority of patients ( . %) had a refractory generalized cse, most patients ( . %) had a non-refractory generalized cse + the others had mostly partial cse. the main reason for intubation was coma (n = , . %). the duration of general anesthesia was not significantly different in refractory cse patients compared to non-refractory cse patients (p = . ). data regarding main outcomes are summarized below-. these preliminary data suggest that the majority of the patients admitted in icu under mv for cse do not have a refractory status. indication of mv is mainly coma without persistent convulsions. the mean duration of general anesthesia before withdrawal is < h, and thus in discrepancy with guidelines, but does not seem associated with a frequent relapse of se. if this low rate of rse for patients admitted in icu and the safety of rapid withdrawal of ga are confirmed, the recommended - h duration of general anesthesia in icu could be challenged. introduction: induced coma in intensive care patients protect them against pain and neurologic disorders. however, a few of them may present a delayed wake-up when the sedation is interrupted. the aim of this work is to assess brain imaging findings in patients with this condition. patients and methods: retrospective review of imaging data of patients ( males and females), aged between and years, admitted in intensive care unit (icu) between june and september , who had sedation or general anesthesia and presented a delayed wake-up. they were explored either by mri (n = ) or computed tomography (ct) (n = ). patients with traumatic lesions were excluded. results: patients were admitted in the icu because of chronic obstructive pulmonary disease exacerbation (n = ), infectious pneumonia or pleural effusion (n = ), acute respiratory failure (n = ), heart disease (n = ). two patients underwent general anesthesia. septic shock and circulatory collapse occurred in and patients respectively. mri and ct showed lesions that may explain the wake-up delay in of and of patients, respectively. brain anomalies included anoxic lesions (n = ) with basal ganglia involvement (n = ), ischemic or hemorrhagic strokes (n = ), hepatic encephalopathy (n = ) and herpetic encephalitis (n = ). conclusion: brain imaging techniques help diagnosing causes of delayed wake-up after induced coma. anoxic lesions and strokes are mostly behind this condition. mri is more accurate than ct. introduction: gastric tubes are common in intensive care units used for enteral feeding, administration of drugs or aspiration of the digestive tract. these tubes offer an excellent tolerance but malposition may have serious consequences that can lead to patient's death. the actualy gold method to confirm their correct placement is chest x-ray. we report a study which evaluate the performance of gastric ultrasonography for the validation of the good positioning of the gastric tube. we carried out a prospective, monocentric study in a medical intensive care units. for each included patient, we compared the results of a gastric ultrasonography to the interpretation of a chest x-ray. results: one hundred and thirteen gastric ultrasonographies were performed from july to may . in cases, ultrasonography concluded that the gastric tube was correctly positioned, confirmed by chest x-ray. in cases, ultrasonography did not visualize the tube in gastric area. among these cases, only malpositions were detected by the chest x-ray. the sensitivity and specificity of gastric ultrasonography were . [ . + . ] and [ . + ]. positive and negative predictive values were and . , respectively. the ultrasonography was performed min [ . + . ] after the gastric tube placement while the chest x-ray was interpreted min [ . + . ] after this same placement (p < . ). our results suggest a good performance of gastric ultrasonography to check the positioning of the gastric tube. this result must be interpreted with caution because of a low power of the study. we planned a multi-center study to confirm our results. giabicani mikhael introduction: prognosis of cirrhotic patients hospitalized in intensive care unit (icu) remains poor. in many icus, cirrhotic patients are widely admitted and revalued after receiving optimal treatments. little is known about risk factors involved in the evaluation of the prognosis at day , except the persistence of organ failure. this susceptibility to organ failure would be related to an alteration of the regulation mechanisms of the systemic inflammatory response. the blood neutrophil-to-lymphocyte ratio (nlr) is an inflammation biomarker reported to predict clinical outcome in unselected critically ill patients and in patients with stable liver cirrhosis, but has never been studied in critically ill cirrhotic patients. the aim of this study was to evaluate the blood nlr as parameter to predict mortality of cirrhotic patients hospitalized > days in icu. retrospective monocentric study including consecutively cirrhotic patients hospitalized in a medical icu from to . for each patient, clinical and biological data at admission and day were collected. nlr at admission ("nlrd "), at day ("nlrd ") and its variation between admission and d ("delta nlr") were calculated. statistical analysis used appropriate non parametric tests and cox regression for survival analysis. the ability of the variables to discriminate survivors from non-survivors was determined using roc curves and a net reclassification index (nri). results: patients (median child-pugh score = [ - ], median meld score = [ - ]) were hospitalized more than days in icu. the major causes for icu admission were sepsis ( . %), gastrointestinal bleeding ( %) or respiratory failure ( . %). patients were followed up for . d . ( %) patients died- ( %) in icu, ( %) after icu discharge and ( %) after hospital discharge. in univariate analysis, factors significantly associated with mortality wereat d , nlr, meld and sofa scores + and between d and d -delta nlr, delta sofa and delta meld. predictors of death in multivariate analysis are shown in table . area under delta nlr roc curve was . (ci = . - . ). nri revealed that delta nlr was more efficient than delta sofa (nri = . %) to identify patients with a % mortality risk at least. conclusion: nlr is a novel inflammation index known to predict poor clinical outcomes. delta nlr is an independent predictor of mortality in critically ill cirrhotic patients and could be more effective than delta sofa in predicting hospital mortality in these patients. severe liver dysfunction acute liver failure related to exertional heatstroke: outcomes, histological features and role of liver introduction: severe acute liver injury and failure (sali alf) is a grave complication of exertional heatstroke (eh). liver transplantation (lt) may be a therapeutic option, but the criteria for, and timing of, transplantation have not been clearly established. the aim of this study was to define the profile of patients who require transplantation in this context. this was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related sali alf with a prothrombin time (pt) lower than %, with or without hepatic encephalopathy. results: male patients (median age- . years) with ali alf related to exertional heatstroke were studied + nine of them ( . %) were listed for emergency lt. the latter differed from those who were not listed with respect to their more severe liver failure after d , a clear deterioration in their pt and alt values between d and d , and more marked organ dysfunction. four of these nine patients were subsequently transplanted. at the time of lt, all had pt levels lower than %, a marked rise in bilirubin levels and required support for at least one organ (or x organs were involved). histological findings on the explanted livers demonstrated massive or sub-massive necrosis and little potential for effective mitosis with a mitonecrotic appearance. the unlisted patients ( . %) were still alive months later and had not experienced any after-effects. conclusion: survival without liver transplantation in patients with heatstroke-related ali alf reaches . %. the indication for liver transplantation is based on an evolving dynamic. the lack of any signs of an improvement in liver function at or after d , in patients presenting with other organ dysfunctions or failure, means that liver transplantation should be envisaged. the peculiar histological features observed on all the explanted livers, and the aspect of abortive mitoses in hepatocytes could be attributed to the effects of heatstroke. . on admission, the mean pt was . % ( - ), the mean total bilirubin was umol l. paracetamol poisoning was the principal etiology with % of the patients- % in the prometheus group versus % in the standard group (p = . ). the hepatic encephalopathy grade was significantly higher in the prometheus group- versus . in the standard group (p = . ). there was no difference between the two groups concerning mortality on day (p = ) or day (p = . ). there was no difference concerning the length of stay in intensive care unit or in hospital between the two groups. patients ( . %) were transplanted. there was a statistical difference between the two groups concerning liver transplantation (p = . )- transplant ( %) in the prometheus group versus transplant ( %) in the standard medical care group. there was a significant improve of encephalopathy after the prometheus session (p = . ). therapy in our icu were included consecutively and prospectively in the cohort. mars ® therapy performed using a double lumen dialysis catheter in the femoral or jugular vein. we used the monitor mars ® tc (teraklin) coupled with the dialysis machine prismaflex ® (gambro). the albumin dialysate circuit consisted of ml of % human albumin and was regenerated by an anion-exchange column and an uncoated charcoal column (diamars ® ie , diamars ® ac ). results: ninety patients were included for sessions. the mean duration was h min (± h min). the population treated consisted of groups-acute-on-chronic liver failure (aoclf), acute liver failure (alf), post-surgery liver failure (post transplantation, post hepatectomy), refractory pruritus and drug intoxication ( fig. ). regarding biological efficacy-total bilirubin was lowered in aoclf and post-surgery groups (p < . ), also in the alf group although not significatively. meld score was lowered in the aoclf and alf group (p < . ). however clinical variables (glasgow score and encephalopathy) didn't improve significatively. in the refractory pruritus group, pruritus decreased in out of patients (p < . ). bile acid levels decreased to . % of its mean baseline level (p < . ). in the drug intoxication group improvement of the richmond agitation-sedation scale (rass) from deeply sedated (rass < = − ) to minimal sedation (rass > = − ) was obtained in out of patients. out of sessions, catheter-related adverse effects were low ( . %), thrombocytopenia was the main adverse effect ( . %). conclusion: we report our mars ® experience with the largest cohort of patients referred from a single hospital. we showed biological efficacy in all indications, although clinical efficacy was uneven. mars ® therapy in patients with refractory pruritus yielded promising results. tolerance was good and the main adverse effect was thrombocytopenia. global transplantation-free survival was low in patients with liver failure, reinforcing the need for a liver transplantation center when using mars ® . introduction: colonoscopy is crucial for the management of lower gastro-intestinal disorders, but its profitability is discussed in critically ill patients, mainly because of the complexity of colonic preparation. as the profitability of colonoscopy in intermediate or intensive care units (cicu) has been scarcely reported ( ), we investigated its indications and usefulness. patients and methods: retrospective bicenter observational study ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . main endpoint: diagnostic profitability of cicu in unselected critically ill patients. profitability was a priori defined as "high" if cicu led to adapt ongoing therapies; allowed an endoscopic intervention; or participated in the decision to limit therapeutic effort. secondary endpoints: describe the quality of cicu and its preparation; determine its position in diagnosis strategy; describe its morbidity. ) + investigation of a gram negative bacilli sepsis (n = , %) + sigmoid volvulus (n = , %) + and cancer diagnosis (n = + %). cicu profitability was deemed high in % (n = ), with an endoscopic intervention performed in % (n = ). the cicu lead to antimicrobial adaptation (n = ), emergent surgery (n = ), or to limit therapeutics effort (n = ). in cases ( %) the cicu was considered normal. patients' preparation was rated as good in % (n = ) + and the colonoscopy was complete in ( %). the cicu was mainly performed as a nd ( %) or rd ( %) investigation after an abdominal ct-scan or an upper digestive endoscopy (respectively performed in first instance in and %). three cicu were complicated by hemodynamic and respiratory failures, none were fatal. discussion: in our series of unselected critically ill patients, cicu were mainly performed to investigate lower gastro-intestinal bleeding. despite a low rate of good preparation, cicu is safe and its profitability is high in the majority of cases. conclusion: although performed in poor conditions, cicu seems useful in the diagnostic and the therapeutic management of critically ill patients, and not only in gastro-intestinal bleeding. ( ) church, surgical endoscopy . introduction: accurate pain assessment is associated with better outcomes in intensive care unit (icu) patients. specific scales for noncommunicative patients have been developed and validated but their routine use still remains inaccurate and subjective. analgesia nociception index (ani) is based on high-frequency heart rate variability. this study objective was to assess the correlation between the behavioral pain scale (bps) and ani during care procedures in deeply sedated patients. we conduced a french multicentric prospective observational study with blinded continuous recording of ani during h with spotting of care procedures in patients with rass less or equal to − . we compared pain assessment using bps and ani before (t ) and during (t ) each care procedure. the cares analyzed included prick glycaemia, turning, catheter insertion, dressing change and others. a behavioral pain reactivity (bpr) was defined by a bps elevation of at least point. we analyzed minimal ani values and its variations with calculation of deltaani (anit -anit ). because of the analysis of several cares per patient we used a bonferroni's correction in comparison of bpr and no bpr groups with a significant p value < . for this comparison. for others analyses the p value considered as significant was p < . . correlation between ani and bps was analyzed using a spearman correlation rank test. introduction: the pain associated with burn was one of the most painful injuries to treat. pain was induced by therapeutic acts such as wound debridement, dressing and other painful procedures. burn pain caused changes in neurophysiology and pharmacokinetics that may make standard pharmacologic analgesic therapy less effective than usual.virtual reality has been explored as an adjunct therapy for the management of acute pain for a number of conditions. in our study, we attempt to assess the impact of virtual reality on management of burn pain during dressing changes. patients and methods: before the therapeutic procedure (dressing changes), the concept of virtual reality therapy was explained to the patient (technology and equipment used). the video used was snow mountain. during the act, pain was assessed until the end of the procedure. the assessment of pain was based on visual analog scale (vas). for pain intensity, the scale was most commonly anchored by "no pain" (score of ) and "very intense pain" (score of ). results: during the study period, patients were included. the mean age was ± years. % of our patients were adults aged over years. they were men and women. the average burned surface area was ± %. pain was evaluated before the start of the therapeutic procedure. the mean initial pain severity score was . ± . (range to ). the pain assessment after virtual reality condition showed a significant decrease in the intensity of pain (p < . ). the mean pain decreased from . to . ± . with extremes ranging from to . conclusion: our study supports the use of virtual reality, simple noninvasive, as an adjunct therapy in the management of pain associated with dressing changes in burn patients. introduction: hypno-analgesia (ha) is used in the operating room and for complex pain. before implementation of ha in our intensive care unit (icu), most protocols for algogenic procedures included intravenous or epidural morphine and nitrous oxid. since , many caregivers have been trained, ha has been implemented and patient comfort is evaluated using ) a specific analogic scale of comfort ( to ) before and after the procedure + ) at the end of the procedure, a score of patient and caregiver comfort using a five item questionnaire ( to points). this pilot prospective study compares ha versus the standard protocol in the removal of abdominal drains after digestive surgery. the main objective was to evaluate the patient comfort before after the procedure using a scale of comfort + the secondary objectives were to test the patient and caregiver comfort scores and evaluate in the impact on consumption of analgesic. between may and september , two groups were obtained, according whether the procedure was performed by ha-trained or non-hatrained professionals (depending on caregivers availability in the unit). the number of subjects required to compare scales of comfort before vs. after drain removal was , using a nonparametric wilcoxon-mann-whitney test. results: eighty-eight patients were analyzed. the mean note in the comfort scale remained unchanged after vs. before drain removal in patients without ha (n = , + . points, ± . ), while it increased in patients with ha (n = , + . , ± . + p = . ). using our specific five item comfort score, patients and caregivers had a comparable level of satisfaction in ha and non-ha groups (patients . and . + caregivers- in both). a trend was observed in reduction of the consumption of morphine and nitrous oxid with ha, without altering their comfort. discussion: despite its limitations (mainly, its open non-randomized design), this study suggests that-ha may be used for algogenic procedures and is willingly adopted in icu by patients and professionals + specific scales scores, adapted for ha, may be useful to assess the effectiveness + finally, ha seems to be at least as efficient as classical procedures and could reduce the use of analgesic drugs. conclusion: ha adds value to patients and to all caregivers. prospective randomized studies are needed to valid the comfort scores we proposed, and to prove that ha reduces the consumption of analgesic drugs. introduction: pain has long been a focus of concern for doctors and caregivers. in intensive care unit, the inability to verbalize discomfort and pain are major stressors for patients. music therapy has demonstrated in many international studies its effect on the blood pressure and on the respiratory frequency. in this context, we conducted a study to evaluate the effects of standardized musical intervention on pain during painful cares in vigils patients hospitalized in critical care. patients and methods: design-we conduct a prospective, observational, randomised, single blind, mono center study. painful cares were studied and then distributed in two groups (n = with music, n = without music). the patients were equiped with a bose© helmet, and had or not music therapy during the care. our main criteria was the pain, it has been evaluated by a numeric scale before and after the painful care. we also estimated anxiety with the covi's heteroevaluation scale before and after the car. we also noticed if the care were stopped because of the pain, then we used a semi quantative numeric scale in order to estimate the feeling of the caregiver and the patient on the session. results: concerning pain, there is no significant difference between the two groups (p > . ). however, in the music group, pain decreased by % after the care (p < . ). anxiety was way lower in the music group than in the group without music (p < . ). we also noticed a decrease of % of the anxiety in the music group. the patients and the caregivers' feeling were the same in the two groups, with no significant difference (p > . ). on the other hand, caregivers tended to underestimate the difficulty of the session in comparison with the patients' (p < . ) in both groups. conclusion: music therapy did not improve the pain in a significant way, in the music group versus the group without but allowed a decrease of % of the pain after the care. nevertheless, music reduced by two patients'anxiety. introduction: sedation and analgesia is one of the basic themes in icu as complications associated with excessive sedation negatively impact the morbidity and mortality of patients. the objective of this study is to show that the nurse implementation of a sedation and analgesia algorithm is beneficial to the patient in terms of sedative drugs reduction and thus overall decrease in duration of mechanical ventilation (mv) and the morbidity and mortality which is associated with it, without altering patient comfort and tolerance of the environment. patients and methods: a before and after prospective, observational, non-interventional study was conducted in surgical icu in caen university hospital, between november and april . mechanically ventilated patients under sedation predicted to last h or more were included. during the "before" period, sedation and analgesia was managed by the physician, while during the "after" period, it was managed by the nurses according to the protocol. results: intubated and mechanically ventilated patients were admitted during the study period. among the eligible patients, were included during "before" period and during "after" period. the duration of mv after inclusion was significantly shorter in group "after" ( . [ + ] vs [ + . ] days, p = . ), as the duration of target rass (- à ) was significantly longer ( the patients experienced less of ventilator-acquired pneumonia (vap) and delirium during the "after" period ( vs . %, p = . , and vs . %, p = . , respectively). the nurse implementation of a sedation and analgesia algorithm was associated with a trend towards reduction in duration of mv, icu and hospital length of stay. moreover, prevalence of vap and delirium was reduced, in correlation to the significant decrease in sedative drugs. this type of algorithm is necessary to reduce morbidity and mortality associated with mv. introduction: central venous catheter insertion is a common practice for anesthetists and intensivsts. this invasive procedure generates pain and anxiety for patients. we aim to demonstrate that remifentanil improves the analgesia during scheduled central venous catheter insertion in mindful patients. patients and methods: a prospective, randomized, double-blind, controlled study in patients requiring central venous access. patients were randomly assigned to receive ng ml − remifentanil target controlled infusion (tci) and local anesthesia (la) with lidocaine or placebo and la. all patients were monitored in intensive care or postintervention care unit and systematically received oxygen. patients were asked to assess verbal numeric rating pain scale (vnrps) during the procedure. the primary outcome was the maximal vnrps. secondary outcomes were pain at each step, anxiety, patient satisfaction, operator ease and side effects. results: ninety patients were included ( in each group). all patients were analyzed. remifentanil significantly reduced maximal pain-vnrps ( % confidence interval [ci] - ) vs ( % ci - ) in the placebo group p = . (table ) . we did not observe any adverse event during this study, and there were no significant difference between the groups regarding side effects. conclusion: tci remifentanil is a safe procedure to reduce pain during central venous catheter insertion in awake patients. trial registration-clinicaltrials.gov identifier- , remidolcath. introduction: although guidelines on post-resuscitation care recommend the use of short-acting agents for sedation during targeted temperature management (ttm) after cardiac arrest (ca), the potential interests of this strategy have not been clinically demonstrated. patients and methods: before-after study. we compared two sedation regimens (propofol-remifentanil, period p vs midazolamfentanyl, period p ) among comatose ttm-treated ca survivors. management protocol, apart from sedation and neuromuscular blockers use, did not change between the two periods. baseline severity was assessed with cardiac-arrest-hospital-prognosis (cahp) score. time to awakening was measured starting from discontinuation of sedation at the end of rewarming. awakening was defined as delayed when it occurred after more than h. results: patients ( in p , in p ) were included. cahp score in p and p did not significantly differ (p = . ). sixty percent of patients awoke in both periods ( vs , p = . ). median time to awakening was . (iqr - ) hours in p vs. (iqr - ) hours in p . awakening was delayed in % in p vs. % of patients in p (p < . ). after adjustment, p was associated with significantly lower odds of delayed awakening (or . , % ci . - . + p < . ). patients in p had significantly more ventilator-free days, and lower catecholamine-free days between admission and day . survival and favorable neurologic outcome at discharge did not differ across periods. time course for awakening according to sedation period. these figures report the time course of patients included after discontinuation of sedation. at each time point, we report in the upper part, proportion of patients awoken after discontinuation of sedation, in the lower part, patients who died without awakening, and in the middle part (in white), patients still comatose. red dots indicate, for each period, the last patient awakening (after days in p and days in p ). black dots indicate the median time to awakening (too early to appear for period ). conclusion: during ttm following resuscitation from ca, sedation with propofol-remifentanil compared with midazolam-fentanyl was associated with an earlier awakening, and an increase in ventilator-free days. the new recommendations of the french society of anesthesia-intensive care (sfar) on perfusion and medication errors were revised in to promote proper use relating to drug administration with medical devices. to advance that of inquiry, practices of our intensive care unit (icu) were assessed in order to improve drug administration by central venous catheter (cvc). patients and methods: prospective evaluation by pharmacist resident and technical nurse during seven weeks, using a standard evaluation tool, in a bed icu. drug recommendations and sfar documents from were used as referential of conformity. the following parameters were evaluated- central venous lines mounting, drug administration and identification with a focus on narrow therapeutic index (nti) drugs. results: patients with cvc were analyzed between june and july . entered directly in the icu. were hospitalized for surgical reasons. had triple-lumen cvc. regarding the first parameter, no conformity was found due to lack of line identification ( %) or anti-return valve well positioned ( %). perfusion ramp position was above heart level in %, infusion tubing had contact with floor in %, and absence of plug on non-used lines is found in % of cases. regarding second parameter, non-conformities were due mostly to syringe label-absence of drug's concentration ( %), preparator identification ( %), patient identification ( . %), drug identification ( . %, all concerning propofol), date and time of medication preparation ( %), lack of color code of labels ( %). regarding nti, % were not administrated according to the recommendations-absence of dedicated line ( %), absence of administration on the nearest insertion site of the catheter ( %). conclusion: the evaluation highlight some improvement axis such as complete identification on syringes, sensitizing of icu healthcare team, or homogenization of cvc perfusion system. it calls for a second evaluation round after implementation of improvements. introduction: sedation is a corner stone of the care of patients receiving mechanical ventilation in the icu. sedation was associated with increased comfort and adherence to care, but also with increased morbidity, including delirium, increased duration of mechanical ventilation and length of icu stay. previous studies reported beneficial impact of reduced doses of sedative drugs and careful monitoring of patients comfort and consciousness. our goal was to assess the impact of the introduction of a nurses-dedicated sedation protocol in our icu. patients and methods: this monocentre retrospective before-after study included all the patients admitted in our icu, over two threemonth periods, from july and january , treated with invasive mechanical ventilation for more than h and older than yrs. after the first period, all physicians and nurses were trained to a new sedation management protocol. analysis was performed to assess the prescription and application of the protocol, its impact on the use of sedative drugs, icu length of stay, and duration of mechanical ventilation. major complications were also recorded. results: patients were included- before and after the protocol implementation. patients in both groups had similar baseline characteristics (men vs. %, p = . + mean age ± vs. ± years, p = . + weight . ± . vs. . ± . kg p = . + igs ± vs. ± , p = . + medical admission vs. %, p = . ). recordings of rass and bps did not differ between groups ( ± vs ± , p = + ± vs, ± , p = . ). the duration of sedation was significantly shorter after introduction of protocol ( . ± . vs . ± . , p < . ), as was the duration of mechanical ventilation ( . ± . vs . ± . , p = . ) and icu length of stay ( . ± . vs . ± . , p = . ). there was no difference in major icu complications, nor in mortality between groups ( and %). conclusion: although the implantation of a sedation protocol did not translate in increased recording of rass and bps scores, it was associated with improved outcomes. our data suggest that, more than the protocol by itself, beneficial effects reported after the implementation of a sedation protocol may be ascribed to increased awareness of the care givers and thus better management of sedation. introduction: workload affects the quality of care and the prognosis of critically ills patients. measuring workload in intensive care units (icu) has thus become essential for allowing a better matching between the activities required and the management of resources. in march , the medical icu of the university hospital of monastir (tunisia) moved into new buildings (more space and beds, computerbased prescriptions and monitoring, etc.). the aim of the present study is to compare the level of workload before and after the change of the icu buildings. patients and methods: during the two study periods (period -july-september and period -july-september ) adult patients consecutively admitted, for more than h, in the medical icu for arf and or sepsis were included in the analysis. data collected were the demographic characteristics (age, sex, body mass index (bmi), comorbidities, simplified acute physiology score (saps) iii), the nursing workload measured using the therapeutic intervention scoring system (tiss- ) and hospital survival. results: thirty-six patients ( male) were included in the study ( during period and during the second period). the medians of age, saps iii and bmi were respectively (iqr = ) years, (iqr = ) and . (iqr = . ). the main comorbidities were hypertension, copd and neurological disease respectively in , and %. the demographic characteristics were similar during the two periods. nurse workload was characterized by m tiss- = (iqr = ) and time of nurse's care of min (iqr = ). these two workload indicators were significantly higher during the second period (table ) . during the second period, "standard monitoring" and "frequent dressing changes" (> time day) were the activities with significant increase from, respectively to % (p < . ) and from to % (p < . ). the relocation of our icu in in new buildings was associated with a significant increase of the nurse workload with regard to patients with arf and or sepsis. . bland-altman analysis showed excellent accuracy and precision between recorded and collected data for all tested variables within clinically significant pre-defined limits of agreement. however, ( . %) data were missing and a delay was observed between videotaped and collected times. this delay was less than s and remained stable through all data for each patient. we identified that the missing data were due to a limit in the number of data being processed in the database at the same time and the delay between data presentation and data collection in the database was due to different server time settings. both technical issues were corrected. conclusion: our study identified two issues in the data collection process that slightly limited the accuracy of our high resolution electronic database. we recommend the performance of such validation study before using a high resolution database for clinical or research purposes. introduction: fluid overload, and also its variations, is known to jeopardize the outcome of icu patients. however, fluid balance remains difficult to assess accurately. in that context, our study aims to assess the prognostic value of body weight variations (bwv) from day to day on the -day mortality, length of stay (los) and the occurrence of ventilator-associated pneumonia (vap) and bedsore in critically ill patients with shock. patients and methods: adult patients admitted in icu with shock between and , and requiring mechanical ventilation during the first h, were extracted from a prospective multicenter cohort for a retrospective analysis. bwv was defined as the difference between the body weight of the day of interest and the body weight on admission. case mix, severity on admission, and outcomes were collected. fine and gray sub-distribution survival models were used, with icu discharge as competing event, adjusted on comorbidity and illness severity at admission at each landmark, from day to day . the impact of bwv on icu stay duration was estimated through a multivariate negative binomial regression model. the median age and saps score of the included patients were (iqr, - ) years and (iqr, - ), respectively. the bwv increased from . kg (iqr, - . ) on day to kg (iqr, − . to . ) on day . the day in-hospital mortality, the icu occurrence of bedsore and vap were , and . %, respectively. four categories of bwv were defined according to bwv interquartiles: weight loss, stable weight, moderate and severe weight gain. categories of bwv were independently associated with death on day and day (day : shr . ; % . - . p = . ; day : shr . ; % ci . - . , p = . ) (fig. ) . a weight loss tended to be associated with increased occurrence of bedsore, and weight gain with increased occurrence of vap. the extent of bwv increased the duration of icu stay independently of other severity factors. discussion: bwv may be another clinically relevant tool to assess the risk of death, mostly after day . the increased risk of bedsore in case of weight loss deserved to be confirmed. conclusion: body weight should be daily monitored for better prognostication. bwv-based restrictive strategies should be further evaluated. the clinical effectiveness of multi-layer silicone dressings in preventing icu acquired pressure ulcers: a randomised controlled trial introduction: the development of pressure ulcers (pu) in critically ill icu patients result in additional morbidity and may contribute to mortality in some cases. the minimisation of icu acquired pu remain an international challenge. this paper describes australian research that used multi-layer soft silicone sacral and heel dressings to prevent pu in critically ill patients. patients and methods: a total of critically ill patients were enrolled into an -month randomised controlled trial in one of melbourne's trauma centres. patients were randomised on admission to the emergency department and either had standard pu prevention or standard care plus the application of prophylactic sacral and heel dressings. patients were observed daily for pu development for the duration of their icu stay. results: patients in the dressing group has significantly reduced incidence rate of pu development compared to patients receiving standard pu prevention alone ( . vs . %, p < . ). patients in the dressings group had a relative risk reduction of % and a % absolute risk reduction for developing a pu regardless of their critical illness. results indicate the number needed to treat to prevent one pu was . additionally, we calculated the cost-benefit of this intervention and found the patients treated with prophylactic dressings cost . time less than the standard care group for wound care. discussion: the use of prophylactic dressings to prevent pu at our hospital have proved to be very effective in icu and subsequent studies have confirmed our results. it appears that the main mechanism of pu protection provided by these dressings is the reduction of pressure and shear forces leading to tissue distortion and cell death rather than the previously accepted ischaemic model of pu development. our current policy is now to use these dressings on all patients with a high risk of developing pu. the use of prophylactic multi-layer silicone dressings to prevent pu in critically ill patients is effective but it does not replace standard pu prevention methods. the use of these dressings sould be considered complimentary to best practice in pu prevention. iatrogenic events in intensive care unit: incidence, risk factors and impact on outcome ayed samia , merhebene takoua introduction: iatrogenic events (ies) are defined as harm resulting from medical intervention and health care, and not explained by underlying disease. mortality is reported to be as high as . % in cohorts of hospitalized patients experiencing ie. both length of stay and cost of hospitalization are increased by ies occurrence. we perform this study to determine the incidence, risk factors, and impact on outcome of ies in intensive care unit (icu). patients and methods: all patients admitted more than h to the -bed icu of a teaching hospital were prospectively screened. patients were monitored daily for adverse clinical occurrences. time and data about each ie were collected and they were considered as preventable or life-threatening events. for each patient, the followings were recorded-basic demographic data, indication for admission, severity scores on admission (sapsii and apacheii), need and duration of mechanical ventilation (mv), length of stay (los) in icu, intensive care work load score (omega), global mortality and ies related mortality. results: during the months period, patients were included and ( . %) were judged to have developed an ie while hospitalized. we recorded ies over days in icu so a density incidence of ie for patient-day. ies were considered preventable in % of cases and life-threatening in % of cases. ies occurred in a mean delay of ± days. global mortality rate was . % and ies related mortality rate was . %. patients with ies were significantly severe on admission, with a longer duration of mv and los in icu. omega score was significantly higher. multivariate analysis showed that omega score was the independent risk factor of ies occurrence (or . ic % [ . - . ], p < - ). dead patients were significantly severe on admission and experienced more ies than survivors. omega score, duration of mv and los were significantly higher. in multivariate analysis, ies and life-threatening ies were independent factors of mortality (or . ic % [ . - . ], p < - and or . ic % [ . - . ], p < - respectively). conclusion: ies in icu are common and frequent but one-third is preventable. work load icu score is the independent risk factor of their occurrence. ies impact largely the outcome especially the lifethreatening ones. efforts must be focused on preventing programs to reduce ies and improve the outcome. introduction: based on the recent sepsis- definitions, septic shock is defined by the combination of vasopressor requirement and serum lactate level > mmol/l. however hyperlactatemia and lactate kinetics may result from both increased production and impaired clearance in the critically ill, and may therefore not only rely on the severity of circulatory failure. we herein addressed the determinants of hyperlactatemia (> mmol/l) and the factors likely to impact on early lactate clearance in septic shock. patients and methods: this was a -year ( - ) monocentric retrospective study. all adult patients diagnosed for septic shock within the first h were included. septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. the first lactate value (l ) was measured at the time of icu admission. hyperlactatemia was defined as a first lactate level > mmol/l. the second value (l ) was measured within h following the first measurement. lactate clearance was calculated as (l -l ) l time between l and l measurements) and expressed in mmol hour. parameters associated with initial hyperlactatemia and lactate clearance were investigated using multivariate logistic regression analysis. introduction: cardiac surgery with cardiopulmonary bypass (cpb) induces immunosuppression which has considerable implications for patients. cpb induces a significant increase in circulating neutrophils. neutrophil activation, associated with production of antibacterial peptides, reactive oxygen species (ros), cytokines, and other inflammatory mediators, as well as release of dna into the extracellular milieu (neutrophil extracellular traps (nets)), plays a central role in innate host defense and modulation of inflammation. however, it has been shown that, in septic shock or systemic inflammation as major surgery, immature circulating neutrophils can induce immunosuppression and increase the risk of secondary infections. staphylococcus aureus (sa) is one of the most commonly encountered bacterial pathogen responsible for poststernotomy mediastinitis, and neutrophils alterations may favor postoperative infections. the main objectives of this study were to evaluate the direct effects of cbp on neutrophils functions and to study the impact of different strains of sa on neutrophils bactericidal functions. patients and methods: blood samples were collected before and h after cardiac surgery with cpb and bone marrow samples were harvested directly after sternotomy, before initiation of cpb, and at the end of cpb, before sternal closure. septic patients were included as controls. circulating neutrophils analysis was performed using flow cytometry. we also studied netosis, ros production and bactericidal activity in isolated neutrophils before and after surgery using two strains of sa-one responsible of postoperative mediastinitis and one isolated from nasal carriage. results: blood cell count with differential demonstrated a significant increase in neutrophils h after surgery. flow cytometry analysis of blood samples indicated neutrophils were matures with a significant increase in degranulation marker (cd b). neutrophils life span was also increased after cbp. flow cytometry analysis of bone marrow samples showed no difference in cell composition and maturation before and after cbp. the neutrophil production of ros was significantly higher after cbp. however, cbp did not impact nets formation, phagocytosis and bactericidial function. moreover, there was no difference regarding the phagocytosis and the bactericidial activity when exposed to the two strain of sa. as expected, immature neutrophils count was significantly increased in septic patients compared to cardiac surgery patients. these results indicate that cbp promotes the recruitment of matures neutrophils via a demargination process. cbp does not induce neutrophil dysfunction. neutrophils should not be targeted to decrease postoperative infection after cpb. introduction: protein tyrosine phosphatase b (ptp b) is a negative regulator of both no production and insulin signaling and has been shown to be an aggravating factor in septic shock. stress hyperglycemia frequently occurs in critically ill patients and is associated with poor outcome. experimental studies on transgenic mice have shown that ptp b deletion resulted in a reduced insulin resistance and in a better survival during experimental model of sepsis. the main objective was to study the correlation between the ptp b gene expression and organ failure (through the delta sofa score between day and day ) or insulin resistance. patients and methods: twenty-seven healthy male volunteers have been included in this clinical trial. the product was administered by continuous intravenous infusion (civ). a single ascending dose design with dose levels was used. cohorts and received a -min single dose of motrem ( and mg and one and two volunteers respectively). then, cohorts to received either a -min loading dose (from . mg kg to mg kg) followed by . -hours maintenance dose (from . mg kg h to mg kg h) of motrem or a matching placebo ( - ratio). all volunteers were carefully monitored. before escalation to the next dose level, safety and pk data of the previous dose level were reviewed by a safety review committee. since immune system is at rest in normal individuals and thus trem- pathway is not activated, no pharmacodynamics parameters were analyzed. the main objectives of this trial was then to study the safety and pharmacokinetic profile of motrem. results: no product related changes in vital signs, clinical nor laboratory parameters were observed. no product-related adverse events were reported. the pk of motrem was linear; the main clearance was estimated at l/h/ kg which is higher than the hepatic blood flow in human (i.e., l/h/ kg) and is therefore indicative of an extensive enzymatic metabolism in blood + effective half-life was calculated to be about min. conclusion: motrem was found to be safe and well tolerated up to the highest dose tested ( mg/kg for a -min loading dose and mg kg h for a . -hours maintenance dose). safety and pharmacokinetics of motrem is currently being studied in septic shock patients in a phase iia randomised, double-blind, two-stage, placebo controlled, international, multicenter clinical trial (www.clinicaltrials.gov nct ). - ) is an immunoreceptor expressed on neutrophils and monocytes macrophages whose role is to amplify the inflammatory response driven by toll-like receptors engagement. the pharmacological inhibition of trem- confers protection in several pre-clinical models of acute inflammation. in this study, we aimed to decipher the role of trem- on the endothelium. we evaluated the expression of trem- in vessels and isolated endothelial cells by flow cytometry, qrt-pcr and confocal microscopy. we generated an endothelium-conditional trem- ko mice and submitted them to polymicrobial sepsis through clp. organs and blood were harvested at different time points and analyzed for cellular content, cytokine chemokine concentrations, and vasoreactivity. survival was monitored for week. results: trem- was expressed in aorta and pulmonary vessels from animals, and inducible after lps stimulation or during sepsis. these results were confirmed in human pulmonary microvascular endothelial cells. the pharmacological inhibition of trem- , using the synthetic inhibitory peptide lr , decreased the lps-induced trem- expression. sepsis induced a profound vascular hyporeactivity in wt animals, both in terms of contractility and endothelium-dependent relaxation. although contractility was still impaired in endotrem- -mice, vasorelaxation was completely restored. soluble trem- concentrations, a marker of trem- activation, were markedly increased in the plasma, the peritoneal lavage fluid and the lungs from wt septic mice compared to control. in endotrem- -mice, strem- level was reduced. plasma concentrations of soluble vcam- and il- were also reduced in endotrem- -animals. we observed an accumulation of neutrophils and inflammatory ly chigh monocytes in the lung of wt septic mice. this accumulation was dampened in endotrem- -mice. by contrast, endothelial trem- deletion favored the accumulation of reparative cells (ly clow monocytes). finally, survival was clearly improved in the endotrem- -group as compared to the wt group. conclusion: we reported that trem- is expressed and inducible in endothelial cells and plays a direct role in vascular inflammation and dysfunction. the targeted deletion of endothelial trem- conferred protection during septic shock in modulating inflammatory cells mobilization and activation, restoring vasoreactivity and improving survival. the effect of trem- on vascular tone, while impressive, deserves further investigations including the design of endothelium specific trem- inhibitors. - . ]. patients suffered from pneumonia, from intra-abdominal sepsis. we measured serum levels of total and free thiamine, thiamine mono di and triphosphate (tmp, tdp and ttp respectively), as well as the erythrocyte transketolase activity and arterial lactate at the time of admission. we also recorded the vital status at the end of the icu stay. results: % of our subjects exhibited particularly low levels of free thiamine (< nmol/l). there was no correlation between free (r = − . ; p = . ), or total (r = − . ; p = . ) thiamine concentration and lactate levels. there was no correlation between tmp (r = . ; p = . ), tdp (r = − . ; p = . ), ttp (r = − . ; p = . ) and lactate levels in the whole population. no correlation was found between the concentration of thiamine derivatives and arterial lactate levels in the subgroup of patients exhibiting the highest levels of lactate (> and > mmol/l). total thiamine and tdp concentration at the time of admission were significantly higher in icu survivors than in non-survivors (p = . and p = . ). during sepsis, we did not find any correlation between thiamine and lactate concentration. lower thiamine diphosphate concentration may be associated with icu-mortality. introduction: a positive fluid balance in sepsis is a determining factor for mortality. in previous experimental studies, sodium lactate has been shown to improve hemodynamic and avoid fluid overload ( ). to understand these beneficial effects, we investigated the impact of sodium lactate on capillary leakage, in comparaison to saline on capillary leak in a rat model. the sixteen sedated, mechanically ventilated rats were challenged with intravenous infusion of e.coli lipopolysaccharide ( mg/kg). two groups of eight animals were randomised to receive a continous perfusion ( ml/kg/h) of sodium lactate . % (treatment group) or . % nacl (control group). in order to inject the same caloric load in the two groups, a . ml/kg/h of either water of % dextrose solution were perfused. mean arterial pressure, heart rate, urine ouput were measured over a min period. an echocardiography was then performed and evans blue ( %, mg/kg) was intravenously injected min before sacrifice. organs were withdrawn and organs wet dry ratio and evans blue dye extravasation were measured. results: fluid balance, organs wet dry ratio and evans blue dye extravasation were not significantly improved in sodium lactate group. hemodynamics parameters were not significantly enhanced after sodium lactate infusion. discussion: previously, lactate administration has improves renal perfusion. in our study, the volume of urine output was decreased in the groups reflecting the severity of our model. and the vascular filling ( . ml/kg/h) higher than in the literature could impact our results. ( ) recently, the pressure electricy index-pmus eadi index (pei) has been described. ( ) the purpose of this study was to assess muscular pressure (pmus) using pei with our nava protocol. patients and methods: observational study, patients recovering from pneumonitis and acute respiratory failure. sbt was pressure support ventilation with cmh of assist and no pep. pei was calculated under nava and during sbt from airway pressure drop during end-expiratory occlusions, muscular pressure (pmus) was estimated from pei ( ) . another index, patient ventilator contribution index (pvbc) was also measured using the inspiratory peak of eadi and vt (inspiratory) during assisted and non-assisted breaths. we calculated pvbc-squared because it has been shown that it is more correlated to pmus ptot. results: results are summarized in the introduction: in icu, intubation is a high risk procedure associated with high morbidity. despite procedure's improvement with systematic application of fluid loading, early use of vasopressors and checklist use, morbidity remains high. first pass success is strongly correlated with adverse event occurrence. a recent study by semler et al. concluded than "sniffing" position is better than "ramped" position to increase first pass success even the primary outcome prespecifiedpulse pressure saturation was not different between the two groups. we conducted a post hoc analysis of the randomized clinical trial macgrath mac video laryngoscope or macintosh laryngoscope for intubation in the intensive care unit (macman) to determine the best position for intubation in the icu. patients and methods: macman was a multicentre, open-label, randomized controlled superiority trial. consecutive patients requiring intubation were randomly allocated to either the mcgrath mac videolaryngoscope or the macintosh laryngoscope, with stratification by centre and operator experience. an only inclusion criterion was-"patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if-contraindication to orotracheal intubation (e.g., unstable spinal lesion); insufficient time to include and randomize the patient (e.g., because of cardiac arrest); age < years; pregnant or breastfeeding woman + correctional facility inmate; patient under guardianship + patient without health insurance; refusal of the patient or next of kin to participate in the study; previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess association between patient position (sniffing or supine) and first pass success. between-groups baseline difference was adjusted for baseline covariates significantly associated with the group membership (p < . ). results: failure of first pass introduction: during acute exacerbation of copd oxygen should be titrated to avoid both hypoxemia and hyperoxia. the recommendations are not followed and automated oxygen titration may be useful in this population. the aim of this study was to evaluate a new device developed to automatically titrate oxygen based on spo target (freeo , oxynov, canada) and to compare oxygenation parameters with usual administration (manual flowmeter). the study is an observational monocentric study. we prospectively included patients hospitalized for acute exacerbation of copd receiving oxygen. written informed consent was obtained from all patient. in the first part of the study, we evaluated oxygen flowrate and spo during min at baseline based on management of the physicians in charge. the oxygenation parameters were compared with automated titration (freeo during h). in the second part of the study, oxygen was delivered with freeo until oxygen weaning or a maximum of h. we evaluated the oxygenation parameters during prolonged utilization, the duration of oxygen administration, a new bluetooth spo connection compared to wire spo connection (evaluated by visual analog scale - ). results: we present preliminary data of copd patients (sex ratio m f = ). mean age (± sd) was ± years, mean fev (± sd) was . ± . l. oxygenation data in both parts of the study are displayed in the table . time in the spo target was significantly increased with freeo in comparison with manual titration and oxygen flowrate was reduced by half. in the second part of the study, the % of time in the spo target with automated oxygen titration was above % and time with hypoxemia and with hyperoxia were low. in patients, we compared comfort with wire spo connection to bluetooth wireless spo connection. the comfort was significantly increased with wireless connection ( . ± . vs. . ± . , p < . ). duration of oxygen administration after inclusion ( . ± . days) and hospital length of stay after inclusion ( . ± . days). conclusion: automated oxygen titration maintains the patients within predetermined spo target more than % of the time and reduces oxygen flowrate in comparison with manual oxygen titration. the second part of the study demonstrates the feasibility to use automated oxygen titration during several days with similar outcomes as previously reported in similar population. there are several limitations of the study and additional evaluations of this device are required. introduction: hyperoxemia occurs up to % of mechanical ventilation days in the icu [ ] and is associated with increased mortality as compared to patients ventilated in normoxemia [ ] . intellivent-asv is a full closed loop ventilation mode adjusting automatically oxygenation's settings fio and peep according to spo for passive and spontaneously breathing mechanically ventilated patients. this post hoc analysis of a monocentric randomized controlled parallel group study compared frequency of hyperoxemia (pao > mmhg and or spo > %) and hypoxemia (pao < mmhg and or spo < %) and the percentage of ventilation time with spo > % and the percentage of ventilation time with spo < % between intellivent-asv and conventional ventilation mode in mechanically ventilated icu patients. the randomized controlled trial was performed in the general icu of hôpital sainte musse, toulon, france. eligible participants were adult aged or over, invasively ventilated for less than h at the time of inclusion with an expected duration of mechanical ventilation of more than h. exclusion criteria were broncho-pleural fistula, ventilation drive disorder and moribund patients. patients were allocated to intellivent-asv group or to conventional ventilation group (volume assist control and pressure support modes) using blocked randomization. the post hoc analysis was performed by the comparison of all arterial blood gases (abg) performed during the study period-the number of abg with hyperoxemia and hypoxemia, the median pao and spo for these arterial blood gases and fio associated were compared according to group. results: patients were included, patients in each group. the total number od abg was (mode conventional) vs (mode intel-livent-asv) (p = ns). the number of abg with pao > mmhg was respectively versus (p = . ) with sao > % was vs (p = . ) with pao < mmhg was vs (p = . ) + with sao < % was vs (p = . ). the percentage of time of ventilation spent with spo > % was % vs (p = . ), and with sao < % was . vs . (p = . ). the continuous control of oxygenation settings provided by intellivent-asv decreases significantly the number of blood gas with hyperoxemia as compared to manual oxygenation setting without increasing the risk of hypoxemia. introduction: in invasively mechanically ventilated patient, dyspnea is frequent and severe. relying on self-report, its measurement remains challenging in patients unable to communicate. a -item observation scale, namely the intensive care-respiratory distress observation scale (ic-rdos), has been proposed as a surrogate of dyspnea-visual analogic scale (d-vas) self-report in intensive care unit (icu) patients [ ] . however this scale has been validated among non-intubated patients and included one item "supplemental oxygen" not thoroughly adapted for intubated population. we sought to develop a dyspnea observation scale more suitable for intubated patients and to evaluate its performance to detect dyspnea. patients and methods: ancillary analysis of data prospectively collected from icu communicative patients enrolled for the validation of the ic-rdos. factorial principal component analysis was first performed to select variables that mostly contributed to the principal axes, among a set of observable variables with possible clinical relevance. to identify the best correlation between these variables and d-vas, were performed an iterative partial least square regression process (pls). iterative pls procedure identified five variables, of which the combination and weighting allowed optimal correlation with d-vas (r = . ; % ci . to . ; p value < . ), which constitute the ic-rdos [ ] . in a first step, we removed "supplemental oxygen", not relevant in intubated patients. we obtained a -items ic-rdos (r = . introduction: lung ultrasound (lus) has emerged in different clinical settings, such as in intensive care medicine (icm). early diagnosis of ventilator-associated pneumonia (vap) remains a challenge to the intensivist. however, scientific evidence is little available on whether lus reliably improves the diagnosis of vap. the aim of this prospective study was to assess whether lus could be an alternative to pulmonary computerized tomography (ct) for assessing diagnosis of vap in icm. patients and methods: twenty-one patients ventilated for duration more than days suspected of vap were included. lus was performed by a well-trained operator who was blinded of the vap diagnosis. the diagnostic gold standard of vap was on the basis of pulmonary ct and positive culture pulmonary. all clinical criteria for the diagnosis were collected the same day of lus and pulmonary ct. the ultrasound exam included anterior, lateral and posterior views from both sides of the chest with superior and inferior views. we classed patient in groups according diagnosis of vap with pulmonary ct (vap + or vap-) and lus (lus + or lus-). lus characteristics of vap diagnosis included profils-asymetric line b (profil a b), without sliding (profil b'), sub pleural consolidation (profil c), consolidation with punctiforme bronchogram (pb), linear air bronchograms (lb) or dynamic bronchograms (lbd), posteror lateral alveolar pleural suffusion (plaps), pleural effusion pathological (pep), shred sign (ss and complications according to insertion site. the advantage of this method is that it gives a pragmatic view of the real clinical situation. patients and methods: ancillary study of the akiki trial, an open pragmatic randomized controlled trial published in , in which patients with severe acute kidney injury were randomly assigned to either an early or a delayed rrt initiation strategy. the present study involved all patients who underwent at least one rrt session. number of rrt catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected. results: among the patients included in akiki, received rrt at least once and patients were finally included in the analysis ( missing data), leading to a total of rrt catheters. femoral site was chosen preferentially (n = , %), followed by jugular site (n = , %) and subclavian site (n = , %). investigating center was the sole factor significantly associated with the choice of insertion site in multivariate analysis (p = . ). higher weight did not affect choice of insertion site. mean duration of catheter use was . (+- . ) days without difference according to site. catheter dysfunction was the main reason for replacement (n = , %). suspicion of infection led to replacement of many catheters (n = , %) but was actually seldom proven (n = , % introduction: long standing dialysis (sled or crrt) allows a better hemodynamic tolerance as well as a greater performance to achieve a negative fluid balance in intensive care unit. dialysis alter hemodynamics mainly by short term variation of blood volume. in this study we took advantage of a continuous monitoring of blood volume during dialysis session to decipher the relationship between the variation of relative blood volume (rbv) with mean arterial pressure (map). this study is observational prospective, including all prolonged (> h) dialysis sessions in saint etienne nephrology intensive care unit between january and june . exclusion criteria were ongoing blood transfusion and blood volume controled ultrafiltration. medical records were compiled along with cardiac ultrasonography at the beginning when available. the statistical analysis was perfomed in two parts. the first part studied the performances of the first hour deltarbv (defined by rbv before minus rbv after h of dialysis) to predict a drop of map below mmhg (hypotension). this analysis excluded sessions with hypotension and intervention during the first hour. the second study was the modelization of the relationship between deltarbv and deltamap for every hour of dialysis without any intervention on blood pressure. both analyses were performed using mixed effects linear and generalized models. fig. vancomycin pk during sled results: a total of sessions on different patients were performed during the period. the characteristics of patients were as follows-sex ratio at , age (sd) . ( . ), weight . kg ( . ), sapsii score . ( . ) . patients on were taken in charge for fluid overload. in the first set of analyses (per sessions), sessions were excluded for intervention in the first hour. the adjusted deltarbv did not predict hypotension during the session (generalized mixed effect model, session and patients set as random effects, estimate . , p = . ). in the second set of analyses (per hour without any intervention), h were analyzed. adjusted deltarbv correlated strongly and inversly with deltamap (linear mixed effect model, random effects were sessions, patients and hour order in the session, estimate . , p < . ). conclusion: in our mostly fluid overloaded patients, the drop of rbv correlated with an increase of map. introduction: kidney transplant recipients (ktr) are at risk of icu admission because of prolonged immunosuppressive therapy and a higher risk of cardiovascular events, severe infections or drug-related toxicities. several retrospectives studies reported the short-term outcome of ktr admitted to the icu, but data concerning the risk of chronic kidney disease and anti-hla immunization are scarce. patients and methods: in this retrospective study, we addressed the in-hospital and long-term mortalities of the ktr admitted in a french icu ( beds) between january and june . predictive factors for death, long-term renal function and hla immunization were identified. results: the main causes for admission were acute respiratory failure ( . %), sepsis ( . %), post-operative period (peritonitis, hemorrhage + %). at the admission, mean age, saps and sofa score were ± years, ± and . ± . , respectively. renal replacement therapy, mechanical ventilation and vasopressors were required in ( . %), ( . %) and ( . %) patients. immunosuppressive regimen was modified in patients ( . % + steroids increase %, calcineurin inhibitors or antimetabolites withdrawal and %, respectively). in-hospital mortality was % ( . and . % at months and ). by multivariate analysis, ebv blood proliferation in the months preceding the admission in the icu, and the saps gravity score at admission independently predicted the in-hospital and long-term mortalities. among the patients alive at month after the admission in the icu and with available data, ( . %) and ( . %) progressed to a more severe ckd stage at months and , respectively. both, the severity of the aki and the preexisting ckd predicted the risk of progression of the ckd. last, de novo anti-hla immunization at month was identified in patients ( . %, donor specific antibodies ( . %)) and was significantly associated with the occurrence of acute transplant rejection (p = . ). in five patients who developed anti-hla antibodies, rbc transfusion during the icu stay was the only immunological trigger identified. discussion: outcome of ktr is closed to the general population admitted in icu and better than other immunocompromised patient, like patients from oncohematology. conclusion: worsening of the renal function and hla immunization are frequent and may impact mid to long-term prognosis because of the high risk of transplant rejection, end-stage renal disease and further transplantation contraindication. introduction: acute kidney injury (aki) is associated with a poor prognosis. although pulmonary embolism (pe) may promote aki through renal congestion or hemodynamic instability, its frequency as its impact on the prognosis of patients with acute pe have been poorly studied. patients and methods: using data from the registro informatizado de la enfermedad tromboembolica venosa (riete) registry, we assessed the frequency of aki at baseline, and its influence on the -day mortality rate of patients with objectively confirmed pe. aki was defined according to the "kidney disease-improving global outcomes" definition. we used multivariate analysis to assess whether or not the presence of aki independently influenced the risk for -day death. the study included , patients with acute pe, of whom ( . %) had aki at baseline. of these, patients ( %) were in stage , ( . %) in stage and ( %) in stage . the proportion of patients with high-risk pe in those with no aki, aki stage , aki stage and aki stage was- . , . , . and %, respectively (p < . ). after days, patients ( . %) had died. overall mortality was- % in patients with no aki, . % in aki stage , % in aki stage , % in aki stage , all p < . ). on multivariable analysis, aki was independently associated with an increased risk of death at days (odds ratio = . + % ci . - . ), after adjusting for the initial severity of pe, age > years, chronic heart failure or chronic lung disease, cancer, anemia and liver cirrhosis. conclusion: one in every - patients with acute pe had aki. moreover aki was an independent predictor of poor outcome in pe patients. this study suggests that pe (and its severity) should be considered as a risk factor for aki and aki may deserve to be evaluated as a prognostic factor in patients with acute pe. introduction: metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (ohca). we aimed to identify risk factors and assessing the impact of metabolic acidosis on outcome after ohca. patients and methods: we included all consecutive ohca patients admitted between and . using admission data, metabolic acidosis was defined by a positive base deficit and was categorized by quartiles. main outcome was survival at icu discharge. factors associated with acidosis severity and with main outcome were evaluated by linear and logistic regression, respectively. results: patients ( . % male, median age years) were included in the analysis. median base deficit was . [ . , . ] meq/l. male gender (p = . ), resuscitation duration (p < . ), initial shockable rhythm (p < . ) and post-resuscitation shock (p < . ) were associated with a deeper acidosis. icu mortality rate increased across base deficit quartiles ( . , . , . and . %, p for trend < . ) and base deficit was independently associated with icu mortality (p < . ). the proportion of cpc patients among icu survivors was similar across base deficit quartiles ( . , . , . and . %, p = . ) and . % of patients with a base deficit higher than . meq l survived to icu discharge with a good neurological recovery. severe metabolic acidosis is frequent in ohca patients and is associated with poorer outcome, in particular due to refractory shock. however, we observed that about % of patients with a very severe metabolic acidosis survived to icu discharge with a good neurological recovery. introduction: precarious socio-economic status can directly influence health, need for hospitalisation and mortality, according to a previous study performed in european countries. similar findings have been reported from anglo-saxon countries in the setting of intensive care. due to the different structure of the healthcare system in france, we aimed to investigate whether socio-economic status influences initial severity of disease and months mortality in patients admitted to intensive care in france. patients and methods: prospective, multicentre, cohort study including adult patients admitted to one of participating intensive care units (icus) between and , and presenting failure of one or more major organs. patients were considered to have a precarious socio-economic status if they presented at least one criterion of social vulnerability or a high epices deprivation score. results: data on social vulnerability were available for patients, of whom . % were considered to be socially vulnerable. compared to non-vulnerable patients, socially vulnerable patients were younger ( . vs . years, p = . ), more frequently had chronic disease ( . vs . %, p = . respectively for congestive heart failure and . %vs . %, p = . for chronic respiratory disease), had higher levels of physical dependency ( . vs . %, p = . ), and were more often classed as having long-term health conditions ( . vs . %, p < . ). conversely, non-vulnerable patients had greater severity of disease at admission to the icu than those classed as vulnerable, both in terms of saps ii and sofa scores (respectively . vs . (p = . ) and . vs . (p = . )). findings were similar after adjusting for major confounders (adjusted odds ratio (or) . , % confidence interval (ci) [ . - . ], p = . ). mortality at months was not significantly different between socially vulnerable patients and those not considered vulnerable, respectively . vs . % (p = . ), even after adjustment for initial severity. conclusion: despite less severe disease at admission to the icu among patients considered socially vulnerable, -month mortality did not differ significantly between those who were socially vulnerable and those who were not. these findings suggest that the french healthcare system provides good protection for the most disadvantaged members of society, particularly when they are admitted to the icu. introduction: an approach of the quality of care may involve assessing the patients' satisfaction. however, the extended caregiverpatient and family relationship, specific to the critically ill patients, may also require to assess the proxies' satisfaction. the opinionfamily tool was developed to assess the satisfaction of the critically ill patients' proxies, in an anonymous and continuous fashion. we conducted a study in the icu of tenon hospital (paris, france) between mars and august . the opinion-family questionnaire, built with categories ( items each), aimed to measure the proxies' satisfaction regarding their perception of the quality of care. all the proxies were invited to express voluntarily and anonymously his her degree of agreement as a response to a statement by the selection of the corresponding stars (strongly disagree- star, disagree- stars, neither agree nor disagree- stars, agree- stars, strongly agree- stars) using a secure touch screen disposed in the waiting room of the icu. results: altogether, patients were hospitalised during the study period, and proxies completed the questionnaire. all the responders spoke french. only responders ( %) answered more than one time. of the responders, ( %) were the referring person, ( %) were children and ( %) were spouses. during the study period, ( %), ( %), and ( %) responders had visited their relative to times, to times, and more than times, respectively. the different categories assessed by the opinionfamily tool were related to «the family and the patient» (fig. a) , «the family and the environment» (fig. b) , and «the family and the caregivers-availability, trust, support, and information» (fig. c) . the corresponding levels of satisfaction (responses of at least stars) were respectively , , , , , and %. some items were associated with a poor satisfaction (participation to the care, identification and availability of the caregivers). conclusion: the implementation of the opinionfamily tool allowed a continuous evaluation of the satisfaction of the critically ill patients' proxies. a systematic implementation of this tool in the icus may be useful to the caregivers for a better understanding of the needs of the proxies. in addition, this tool may allow rapid changes in icu organizations and behaviours to improve the proxies' satisfaction, which may ultimately, improve the care of patients. many factors influence end-of-life decisions (eol). we describe eol decisions in patients with acute respiratory failure and their impact on patients' prognosis. patients and methods: an international observational study included all patients with acute respiratory distress over a -month period. icu in countries were involved. demographic, clinical and biological data were compared between patients with and without decision of lst limitation. we also compared surviving patients after lst limitation decision to those who eventually died. results: among the patients, mortality was . %. a decision of lst limitation was reported in patients ( . %). in univariate analysis, patients with lst limitation decision were older and more frequently hospitalized for a medical condition, had a lower body weight, a higher sofa score, and presented active neoplasia immunosuppression or chronic liver failure more frequently (p < . for all). patients admitted after trauma, drug overdose or pulmonary contusion were less subject to have an lst limitation decision (p < . ). in contrast, patients with non-cardiogenic shock were more subject to these decisions (p = . ). eol decisions were less frequent in lower-middle income countries as compared to high and middle-high income countries (p < . ). multivariate analysis will be presented. among patients with an lst limitation decision, survived ( . %). mortality was higher in this group than in the whole study population (p = . ). in univariate analysis, death after decision of lst limitation was associated with admission for a medical condition (p = . ), severe ards, higher inspiratory pressure, non-cardiogenic shock, higher sofa score with or without respiratory component and chronic liver failure (p < = . for all). on the contrary, admission for trauma was associated with survival (p = . ). regarding the patients who died during their hospital stay, did not receive a decision of lst limitation ( . %). decision of lst limitation was more frequent in older patients (p < . ) and in high-income countries. conclusion: decisions of lst limitation are frequent in the icu, and are associated with increased age and medical severity. however, a significant percentage of these patients survived. interestingly, almost half of the patients who eventually died during their hospital stay had not been subject of a decision of lst limitation. evaluation of the decision-making process leading to a decision not to readmit a patient to the intensive care unit during a same hospital stay introduction: the risk-benefit ratio of (re-)admission to the intensive care unit (icu) has been widely discussed in the literature. however, the ethics of non-readmission during a single hospital stay have not been widely addressed. a decision not to re-admit a patient to the icu could be seen as a limitation of therapy, thus falling within the scope of the law dated april , by denying the patient access to potentially-available healthcare resources. in this context, we aimed to-( ) investigate whether decisions not to re-admit patients to the icu are taken in accordance with french legislation + and ( ) identify the characteristics of patients concerned by this type of decision. patients and methods: this study was based on data from the prospective, multicentre ivoire cohort (influence of socio-economic vulnerability on initial severity and prognosis of patients admitted to the icu + phrc-ir ). we identified patients included in two large regional university hospitals in the east of france for whom a decision not to re-admit was taken during a single hospital stay. the decisionmaking process was evaluated based on a questionnaire comprising items developed by a sociologist from semi-directive interviews with clinicians. results: among patients discharged from the icu alive, a decision not to re-admit to the icu during a same hospital stay was noted in the medical file of patients ( . %). this decision was primarily made on the day of discharge ( . %), and those involved in the decision included-the family, an outside consultant, and the patient themselves in , . and . % of cases respectively. the decision was justified in medical terms in . % of cases, and the main reasons cited were-( ) therapeutic impasse ( . %) + ( ) comorbidities ( . %) + ( ) degree of dependence of the patient ( . %). patients concerned by decisions of this type were generally older ( vs . years, p < . ), with more comorbidities (median vs , p = . ), greater loss of dependence according to katz's activities of daily living ( vs , p < . ), and longer duration of life-sustaining therapies ( . vs days, p = . ). conclusion: although the profile of the patients identified in this study likely justified the decision not to re-admit the patient to the icu, there is room for improvement in the decision-making process. introduction: most of organ donors are brain dead patients. in some cases, patients are identified as potential donors before brain death and will undergo intubation and mechanical ventilation for the sole purpose of awaiting brain death. the aim of this study is to evaluate the practices of professionals in charge of potential donors. (table ). in this case, the issue of organ donation was addressed to the relatives before intubation by % of icup and % of non icup (p = . ). % of participants never addressed organ donation before the brain death. for the % who have done so at least once, organ harvesting never happened in % of cases. legitimacy and difficulties ( table )- % of respondents felt that when a decision of treatment withdrawal or withholding is taken, the patient should not go to icu for any reason and % think that these patients should be allowed to die "quietly". the prospect of an extubation if brain death does not occur or in case of organ donation refusal is a problem for % of icup and % of non icup (p = . ). % of icup and % of non icup think they would need to receive training. conclusion: this study shows that pursuing mechanical ventilation for the sole purpose of awaiting brain death and organ harvesting is a common practice, and that intubating a patient for this purpose alone is done in most of cases but could still be more generalized. on the other hand, information to the relatives should be improved. - . ] . the effect of pp on the monitored parameters varies significantly between each patient but also between each session for the same patient. in positive responders, the effect continues statistically for to h depending on the parameter studied- . h for vd vt, . for phase slope, for petco and for cdyn. the maximum effect of prone positioning on selected parameters seems to be obtained after h of therapy. the acute respiratory distress syndrome (ards) is characterized by lung infiltration with activated neutrophils. neutrophil extracellular traps (nets) are antimicrobial structures released by neutrophils. nets have also been associated with tissue damage in experimental models of acute lung injury. whether nets are involved in the pathogenesis of human ards and could be a potential therapeutic target is unknown. we aimed to quantify alveolar nets production in patients with pneumonia and ards and assess its relationship with outcomes. patients and methods: prospective monocentric study. patients admitted in the icu in with pneumonia and moderate severe ards were included. immunosuppressed patients were excluded. nets (dnamyeloperoxidase) levels were measured by elisa in broncho-alveolar lavage (bal) fluid and serum samples of ards patients and in those of control patients (n = ). patients with higher and lower bal fluid nets levels were compared using the median as a cutoff value. results: thirty-five patients with bacterial (n = ), viral (n = ) or non-microbiologically documented (n = ) pneumonia and ards were included. nets levels were significantly higher in bal fluid than in blood of ards but not of control patients (fig. introduction: the ratio of arterial oxygen partial pressure to fractional inspired oxygen (pao fio or p f) is daily used to assess patients' evolution under ventilatory support. some studies reported the reliability of percutaneous oxygen saturation (spo ) to appreciate pao easy to get on bedside. thus two equations have been proposed-rice equation and ellis equation. however, no large prospective study assessed the reliability of such equations to estimate the p f at the bedside in real conditions. using the spectrum (severe hypoxemia-preva-lence, treatment and outcome) study, we aimed to evaluate the reliability of spo obtained by rice and ellis equation. this study is a planned companion of spec-trum study, a recent prevalence-point-day conducted by the srlf trial group in french-speaking icu aiming to report the patterns and outcomes of hypoxemic patients (defined by p f < mmhg). we included in the analysis all patients under mechanical ventilation with spo < % (according to limit of the rice study). spo and fio were measured simultaneously to arterial blood gas were drawn. results: among patients of the spectrum study, were on mechanical ventilation and had undergone arterial blood gas with simultaneously recorded spo and fio . of note, p f was < mmhg for + between and for + and between and for . pairwise correlations of truth p f with estimated p f was good (rice-spearman's rho = . , p < . -ellis-rho = . p < . ). bland-altmann test showed an important variability of results (p f vs rice (figure) - . ± . -p f vs ellis- . ± . ). the variability decreased with lower p f. caution may be used to interpret our results because we did not reported the quality of spo signal at the bedside. conclusion: regarding the variability of the results, whatever the used equation, caution may be used to predict the p f by the spo fio ratio in patients under mechanical ventilation. introduction: morbid obesity and ards both affect respiratory mechanics mainly through their respective impacts on chest wall and lung elastances. we present a unique series of patients combining very severe morbid obesity and moderate to severe acute respiratory distress syndrome (ards). we describe the use of trans-pulmonary pressures (tpp) measurements for optimization of external peep setting. patients and methods: the monocentric observational study was performed in morbidly obese patients admitted for moderate to severe ards. we performed an incremental peep trial ( cm h o steps) with tpp measurement (nutrivent probe, sidam, italy) in a semirecumbent position as previously described. a decremental peep trial after a recruitment maneuver was not performed since the safety of such a maneuver in this specific population is largely unknown. we defined two ways for determination of external peep setting-( ) peep necessary to obtain a positive expiratory tpp and ( ) peep necessary to obtain a plateau pressure between and cm h o (maximal alveolar recruitment express strategy). data are expressed as numbers (%) and medians (interquartile range). statistical analysis was made using the xlstat software. results: we enrolled during years morbidly obese patients (bmi (ir - )) admitted for a moderate to severe ards. clinical characteristics are displayed in table . the express strategy indicated a peep setting of cm h o (ir - ) whereas tpp-guided peep was cm h o (ir - ), p = . . driving pressure was higher in the express strategy peep setting ( . cm h (ir - )) than in the tpp-guided peep ( . cm h (ir . - )), p = . . tpp-guided peep setting was higher than indicated by the express strategy in all but one patient. one patient suffered from transient hypotension when external peep was set at cm h o, while no patient displayed an inspiratory tpp higher than cm h o. additional data will be provided during the meeting-pressure-volume curve at zeep ( patients), crf measurements ( patients) and abg and capnometry values at each peep level ( patients) . in our ards patients with extremely severe obesity, an incremental peep trial with tpp measurements appeared to be safe and indicated a peep setting significantly higher than for the commonly-used ards strategies. such an approach deserves further comparisons with other modalities of monitoring, such as crf measurements, eit studies, etc. severe poisoning by cardiotoxic drugs and circulatory assistance: -year experience at french university hospital tardif elsa , conil jean-marie , georges bernard , marcheix bertrand , crognier laure , bounes fanny , delmas clement chu rangueil, toulouse, france correspondence: tardif elsa -tardif.elsa@gmail.com annals of intensive care , (suppl ):f- introduction: toxicity from cardiac drugs is associated with a large number of fatalities, significant morbidity and healthcare consequences. severity of these poisonings can be explained by a refractory cardiogenic shock not responding to optimal conventional treatment. criteria of circulatory assistance indications remain unclear. the aim of the study was to describe and to compare patients intoxicated by cardiotoxic drug treated with or without veno-arterial extracorporeal membrane oxygenation (va ecmo). patients and methods: retrospective cohort study conducted at french university hospital. all patients intoxicated with cardiotoxic drugs between january and march were included. patients were divided into groups-with and without va ecmo. results: among the patients included in the study, patients were treated with va ecmo ( %) and patients with conventional therapies. ecmo was respectively employed for refractory shock and cardiac arrest in and cases, all patient required vasopressor support. in-hospital mortality was . % and was significantly higher in the ecmo group ( . %). beta-blockers with membrane stabilizing activity and non-dihydropyridine calcium channel blockers poisoning were the most commonly reported in the ecmo group. mean time from hospital admission to initiation of ecmo was h and the average ecmo duration was . days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . no serious adverse reaction was reported during this period. results expressed in median value ± confidence interval conclusion: refractory cardiogenic shock following cardiotoxic drug poisoning requiring circulatory assistance is associated with significant mortality. even if its use seems justified by the literature, the implantation criteria must be specified and this after an optimal conventional treatment to prevent multiple organ failure. the cdv of patients in the edass group was significantly higher (p < . ) at all-time points after the introduction of catecholamines than among those without edass, as early as h from catecholamine initiation (fig. ) . a strategy in two steps (cdv > µg kg at h and or cdv > µg kg at h) was able to predict edass with sensitivity of %, specificity %, positive predictive value % and negative predictive value %. overall, this two-step strategy identified high-risk patients at h, of whom presented edass. conclusion: overall, our results confirm that early death directly attributable to septic shock could be effectively predicted by the cdv in the first hours of treatment. these results will help to select patients eligible for innovative therapies aimed at improving early mortality in septic shock. introduction: in patients with cardiac arrest, end-tidal co (etco ) has been proposed to monitor the efficacy of cardiopulmonary resuscitation (cpr) but uncertainty persists on its interpretation. we hypothesized that exhaled co may also by affected by occurrence of "lung airways" collapse previously noticed during cpr. because this closure may possibly also limit oxygenation + analysis of the entire exhaled co time waveform-may give information of high clinical value to manage cpr. we report preliminary results from a clinical and bench study aimed at describing the pattern of the capnogram during cpr. induces a systemic inflammatory response associated with an immune dysregulation and a significant pulmonary dysfunction which has been well characterized. surprisingly, there are only a few data available on immunological changes induced by ecls. we believe that ecls leads to immune dysfunction that could expose patients to nosocomial infections. patients and methods: a two-phase study was lead. first we analyzed blood cell count with differential (including lymphocyte, neutrophils and monocyte counts) in all patients who received ecls in our institution from to within the first week following ecls initiation. secondly, monocytes, granulocytes, dendritic cells and lymphocytes function were assessed at day , day and day using flow cytometry and functional tests in patients receiving ecls and compared to patients with cardiogenic shock without ecls. results: among patients with elcs we found an early and persistent lymphopenia and a late neutrophilia (found to be associated with poor outcome in critically ill patients). compared to control (n = ), we found in patients who received ecls (n = ) a significant increase in immature granulocytes ( . ± . on day one versus . ± ± , p = . ) and lymphocytes apoptosis. ecls induced changes in myeloid derived suppressors cells proportion ( . % ± . on day three versus . % ± . before ecls, p = . ), which has been recently associated with a higher incidence of nosocomial infections and seems to be major actors of sepsis-induced immune suppression. complement component a receptor (c ar) from the neutrophil cell surface, was also decreased after ecls initiation (ratio of mean fluorescence index . ± . on day one, p = . ) which is a sign of complement-induced neutrophil dysfunction in septic patients. conclusion: ecls induces quantitative and qualitative leukocytes dysfunctions that can lead to a greater susceptibility to nosocomial infections which contribute to the poor outcome observed in several studies. introduction: aspiration pneumonia is a common complication of cardiac arrest. although its real incidence remains undetermined, probabilist antibiotherapy is frequently or even systematically prescribed in these cases. we assessed the incidence of out-of-hospital cardiac arrest-related aspiration pneumonia and the impact of a microbiological documentation in regard to antibiotherapy course. patients and methods: all patients admitted for out-of-hospital cardiac arrest from to were studied. in our icu, aspiration pneumonia is suspected when a clinical syndrome (fever, per resuscitation constatation) and or chest radiography infiltrates were present. in case of suspected aspiration pneumonia, a microbiological documentation was performed before initiation of probabilist treatment with amoxicillin-clavulanate. we retrospectively defined if patients have aspiration pneumonia using the following criteria-per resuscitation constatation, chest radiography infiltrates, fever. the number of microbiological documentation leading to an antibiotherapy modification was recorded as well as pathogens types. data are expressed as numbers (%) and medians (interquartile range). statistical analysis was made as appropriate using the xlstat software. results: patients were studied. clinical characteristics are displayed in table . ( ) received a probabilist antibiotherapy and ( ) were retrospectively considered with aspiration pneumonitia. results of microbiological documentation were ( ) positive microbiological sample and ( ) with a positive threshold whose ( ) were considered colonized (i.e. no clinico-radiological sign). on the entire positive culture sample, ( ) were positive with oropharyngeal flora as unique pathogen, ( ) introduction: this study aimed to assess whether augmented renal clearance (arc) impacts negatively on piperacillin-tazobactam pharmacokinetic pharmacodynamics (pk pd) target attainment in critically ill patients receiving g day by continuous infusion. patients and methods: over an -month period, all critically ill patients treated by piperacillin-tazobactam for a suspected or documented sepsis without renal impairment were eligible. during the first three days of antimicrobial therapy, every patient underwent -hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at steady state. the main pk pd outcome investigated in this study was the rate of empirical target non-attainment using a theoretical target mic of mg l − for piperacillin and mg l − for tazobactam. the secondary clinical outcome was the rate of therapeutic failure in microbiologically documented infections, defined as an impaired clinical response with a need for escalating antibiotics during treatment and or within days after end-of-treatment. over the study period, patients were included in the primary pharmacological analysis and in the secondary clinical analysis. using a mic of mg l − for piperacillin, the rate of empirical target non-attainment in the overall population was %, with a strong association with crcl ( fig. introduction: invasive fungal infections are a major burden in solid organ transplantation, especially in patients receiving liver graft. however, their incidence has decreased thanks to the development of an antifungal prophylaxis in the post-transplantation period. in patients at high risk of invasive fungal infection (ifi), this strategy is recommended, whereas its benefit remains controversial in low-risk patients. however, there is no clear definition of these two patients groups. our aim was to provide recent data on epidemiology, mortality and ifi risk factors in the early post-operative course in a population without any antifungal prophylaxis. results: the number of beta-lactam antibiotics was . of these requests, half were for piperacillin ( . %), and onethird were for amoxicillin ( . %). the other dosages were mainly for cloxacillin, cefepime, cefotaxime and ceftriaxone. the results confirmed that serum concentrations of piperacillin ( . ± . vs . ± . mg l − < . ) and amoxicillin ( . ± . vs ± mg l − < . ) significantly were higher in patients with neurological disorders or wakefulness delays. the roc curves allowed the predictive values associated with the presence of neurological disorders attributable to antibiotic treatment, corresponding to residual serum concentrations of piperacillin of mg l − and amoxicillin of mg l − . a predictive value for neurological disorders of these concentrations is proposed for residual serum concentrations greater than mg l − for both antibiotics ( % specificity and sensitivity). conclusion: our results suggest that there is an association between a residual concentration of piperacillin and amoxicillin greater than mg l − and the occurrence of neurological disorders. pharmacological therapeutic monitoring of beta-lactams in critically ill patients may be a useful intervention to optimize the antibiotic regimens and to avoid antibiotic-related toxicities. ( ) ( ) ( ) ( ) ( ) . patients with a gnb-bsi were included and were divided into two groups according to the resistance (r) profile (bsi due to a r isolate or not). the following resistances were considered-all gnb-bsi including pseudomonas spp., acinetobacter spp., stenotrophomonas spp. and enterobacteriacae (eb) for which the following antimicrobial resistances were considered-ticarcillin and ceftazidime (cefta) (pseudomonas (pa)), third generation cephalosporin ( gc) (eb) and imipenem (all gnb). after variable selection using random forest and univariable mixed logistic regression models, a multivariable analyses using a mixed model with a random effect (center). sub-group analyses were performed according to species (pa and eb) and resistance for eb. results: from , patients admitted in an annual median of french icus, experienced an icu-acquired (> h.) bsi, ( %) bsi due to gnb, including ( %) bsi due to r isolates. pa was identified in ( %) (mdr-pa bsis ( %)) and eb in ( %) (mdr-eb bsis ( ( %)). the raw mortality rate was % in the overall population and % in the patient with gnb bsi. it was significantly higher for r gnb bsi ( vs % for susceptible gnb bsi, p < . ). after adequate adjustment in a multivariate analysis, we showed that r-gnb bsi was significantly associated with mortality compared to susceptible strains (fig. ) . by considering species subgroup, the effect was not significant for resistant pseudomonas aeruginosa (p = . ) but remained significant when considering only eb. considering eb resistance, the impact of gc r showed a trend to an increased mortality risk whatever there was no effect of imi r (n = ( %)) on prognosis. limitation-the absence of information about antibiotic consumption may partly explain the remaining significant center random effect in the final models. conclusion: in a large french database, after adequate adjustment on prognostic factors, resistant bgn-bsi was associated with a higher icu mortality than susceptible one. the effect was mainly due to eb gc r. severely injured group versus . ± . days for the non-severely injured patients (p < . ). in multivariate analysis, heart rate (> min) and vittel score (≥ criterias) were related to the probability of belonging to the severely injured group (p = . ). the -hour mortality rate was . % in the ed and the -day mortality rate was . %. the development of a network in the ed hosting non vital polytraumas remains crucial. its primary goal will be to meet technical and time requirements and establish in-hospital triage algorithms based on clinical variables, in order to detect these patients at an early stage and offer them priority care in our overcrowded eds. introduction: the trauma of traffic accidents and particularly cranial trauma are, due to their frequency and severe consequences in both the short and long term, a real public health scourge on a global scale. studies of the epidemiology of cranial trauma by traffic accidents and their prognosis are rare at least in underdeveloped or developing countries. in addition, the impact of extracranial lesions on cranial trauma prognosis has long been discussed. the purposes of our study were to examine the epidemiological aspects and to determine the factors correlated to the immediate and distant prognosis of isolated cranial trauma. patients and methods: retrospective cohort spread over years (from to ) and including patients with isolated cranial trauma by traffic accidents (mean age . years, sex ratio- ). we proposed to study the factors correlated with a poor prognosis in terms of death in hospital and glasgow outcome scale (gos) at months unfavorable in dual analysis (univariate and then multivariate). for the gos study, patients were divided into groups-gos favorable for patients with good recovery (gos = ), recovery with a light handicap (gos = ), gos unfavorable for those having survived with a severe disability (gos = ), a vegetative or pauci-relational state (gos = ) and those who died (gos class ). results: hospital mortality was % and the gos at months was distributed as follows: death ( . %), vegetative state ( . %), severe disability ( . %), mild disability ( %) and good recovery ( . %). the -month gos was deemed unfavorable in . % of the cases. various after effects were observed in survivors: physical ( %) dominated by headache ( . %), sleep disorders ( . %) and epilepsy ( . %); memory disorders ( . %) or concentration ( . %) and finally emotional after effects ( . %) with irritability ( . %) and aggressiveness ( . %). in multivariate statistical analysis, independent predictors of mortality were arterial hypotension, hypoxia extradural hematoma (edh),, acute subdural hematomas (sdh), diffuse axonal injury and ventilator associated pneumonia. those correlated with an unfavorable gos were an age ≥ years, hypotension, cerebral edema, coma duration ≥ . days, edh and h glucose ≥ . mmol/l. conclusion: although the short-term prognosis of head trauma seems to be improved at present, the long-term consequences of cranial trauma remain fairly frequent, and often underestimated, which underlines the importance of their screening and their proper care. the average age of the survivors ( . ± . years) was lower than the mean age of the deceased ( . ± . ). ra was the cause of the trauma in % of the cases followed by the fall found cat % of the patients. prehospital care only concerned % of patients. the univariate analysis showed that the main factors of occurrence of death were age (p = . ), glasgow score (p = . ) anisocoria (p = . ), shock (p = . ) % of deaths were due to intracranial hypertension, haemorrhagic shock in % of patients and ards in % of polytrauma patients. conclusion: the management of polytrauma can not be improvised. the medical teams must be coordinated by an emergency physician in prehospital, a doctor anesthesiologist-resuscitator at the reception. some systematic gestures such as preparation of the reception allow to optimize the management of the time. introduction: benign cranial trauma is a major public health problem due to both its frequency and the health costs it creates. the aim of this study was to identify relevant clinical factors that could predict the achievement of brain ct and situations at risk for neurosurgical care and for which ct was a necessity. patients and methods: this is a month prospective study, including patients with benign traumatic brain injury (glasgow coma score gcs ≥ ), patients under years of age and patients with gcs < were excluded. epidemiological, clinical, paraclinical, therapeutic and evolutionary parameters were studied. a multivariate and univariate statistical study was carried out to reveal the predictive factors of a ct anomaly and the predictive factors for the neurosurgical care. data were entered and analyzed using spss . and excel software. results: the average age of patients was years with a predominance of male, and sex ratio of . . the cause of the btb was mainly represented by the accidents of the public road in . % of the cases. . % of the patients were asymptomatic, the most common symptomatology was dominated by the initial loss of consciousness ( . %), headache ( . %). the glasgow coma score was distributed as follows-gcs ( . %), gcs ( . %) and ( . %). . % of patients had clinical signs of trauma to the skulland or face. brain ct was performed in . % of patients, and . % had abnormal ct. the use of neurosurgical care was of the order of . %. in univariate analysis-the predictive factors for a ct abnormality were the intoxication during the brain trauma, the gcs < , signs of trauma in the skull face, the vomiting, the initial loss of consciousness, the comitial crisis and the predictive factors of neurosurgical care were the gcs < , the anisocoria, headache, the vomiting, the amnesia, the initial loss of consciousness, the comitial crisis, the anormal ct, the extradural hematoma or the subdural hematomat in multivariate analysis-the predictive factors for a ct abnormality were the gcs < , the initial loss of consciousness and the predictive factors for the use of neurosurgical care were the gcs < , signs of trauma in the skull face, the amnesia, the comitial crisis, the hsd. conclusion: an algorithm must be applied in collaboration between resuscitators and neurosurgeons to improve the quality of benign cranial trauma management. prognostic value of hyperchloremia in patients with traumatic brain injury: a prospective observational study taghouti introduction: background-traumatic brain injuries (tbi) are a major public health problem. they are the leading cause of death among those aged less than years. hyperchloremia is a common electrolyte disturbance in patients with tbi. hyperchloremia has been associated with increased morbidity and mortality in critically ill patients + however, its prognostic significance in tbi patients is poorly documented. the aim of this study is to describe the prevalence and outcomes of hyperchloremia in patients with tbi admitted to the intensive care unit. patients and methods: in a prospective design, we included consecutive patients with tbi ( males + median age- years) admitted to the icu in charles nicolle hospital of tunis from mars to september . adult patients (aged ≥ years) with isolated tbi or associated with minor extra-cranial injuries (defined as all non-head abbreviated injury scale < ) were included. hyperchloremia was defined as a chloride level > meg/l. clinical and laboratory variables were compared between survivors (n = ) and non-survivors (n = ). we assessed the association between hyperchloremia -h post-admission and -day mortality. p < . was taken to indicate statistical significance. results: the median sofa score at t was points and the median igs score was points. the median iss was points. there were cases of mild head injury, moderate head injury and severe head injury. the -day mortality was %. hyperchloremia occurred in patients ( %) and the incidence was significantly different between survivors and non-survivors ( vs. %, respectively, p < . ). in addition to hyperchloremia (p = . ), other laboratory variables were associated with -day mortality-hypernatremia (p = . ) and hypoalbuminemia (p = . ). conclusion: hyperchloremia -h post-admission was associated with -day mortality in patients with tbi. this index could be useful prognostic marker. efforts should focus on the prevention of hypernatremia and hyperchloremia in this vulnerable group of critically ill patients. child traumatic brain injury naili amine blida rp, algÉrie correspondence: naili amine -drnailiamine@yahoo.fr annals of intensive care , (suppl ):p- introduction: brain injury in children is common and mild in most cases, but it remains the leading cause of death and disability in children over year of age worldwide. the peculiarity of the child is that he possesses not mature brain and that the consequences of injuries acquired by traumatic brain injury can lead to the loss of capacities, as well as the non-acquisition of function, but above all the risk impact on learning abilities. the objective of the study is to define the incidence rate of cranial trauma in children as well as the mortality and morbidity of this scourge which presents a major public health problem. patients and methods: it is a descriptive retrospective study of a series of children hospitalized in neuro-resuscitation service during the period january to december , , including children admitted for cranial trauma. clinical, para-clinical, etiological and therapeutic data were collected from hospitalization records. results: in a series of children hospitalized during the defined period, children were admitted for cranial trauma, i.e. a frequency of %. the average age was years [ h of life- years], with a sex ration of among the children, had severe head trauma, a rate of % + whose causes are variable- road accidents, domestic accidents, traffic accidents, and obstetric accident, admitted with a pediatric glasgow score between and , and all required mechanical ventilation of the head trauma, were operated for different lesions- extra-dural hematomas, cranio-cerebral wounds, subdural hematomas, decompressive craniectomy, and embarrure. children had died following severe head trauma, i.e. a mortality rate of %, the morbidity rate of head trauma in the tipaza wilaya was . , children year, the average length of stay in intensive care units was days, with several complications of decubitus, and functional due to the primary and secondary lesions of the cranial trauma. the head trauma of the child is a public health problem, its functional prognosis can be dramatic when it is severe, its management must be early and multidisciplinary. introduction: the aim of the study was to identify factors predicting lung contusion in trauma children. patients and methods: retrospective study conducted for a period of years (january , -december , ) in a medical surgical intensive care unit. all trauma patients younger than years were included. two groups were compared-those with lung contusions (c + group) and those without lung contusions (c − group). results: we included patients. the mean (sd) age was . ( . ) years. chest injury was diagnosed in patients ( . %). all our patients needed mechanical ventilation. lung contusions were diagnosed in patients ( % of all patients and . % of patients with chest trauma). in multivariate analysis, independent factors predicting lung contusion were road traffic accident (odds ratio [or], . + % confidence interval [ci], . - . + p = . ), increased pediatric risk of mortality (prism) score (or, . + % ci . - . + p = . ), hepatic contusion (or . + % ci . - . + p = . ), and pelvic ring fracture (or, . + % ci . - . + p = . ). death occurred in patients ( . %). intensive care unit mortality was significantly higher in the c + group (or, . + % ci . - . + p = . ). however, mortality was not differentbetween the groups after adjusting for prism score (or, . + % ci . - . + p = . ) or after adjusting for injury severity score (or, . + % ci . - . + p = . ). conclusion: lung contusion is common in critically ill children with chest trauma. the diagnosis should be considered in patientswith road traffic accident, increased prism score, hepatic contusion, and pelvic ring fracture. introduction: chest trauma is often associated with pleural effusion (hemothorax and or pneumothorax). drainage of the pleural space by a chest tube is a common intervention in such situations. blunt dissection technique with a kelly clamp is preferred to classical trocar techniques to prevent severe complications, like perforation of thoracic or abdominal organs. despite these precautions, malposition remains the most common complication of tube thoracostomy. we investigated a new technique of bougie-assisted chest tube insertion to prevent chest tube malposition after chest drainage of post traumatic pleural effusion. patients and methods: we performed a controlled before-and-after study to assess the ability of a bougie-assisted chest tube insertion technique, compared to a standard blunt dissection technique, to prevent chest tube malposition. for the bougie-assisted group, we used a disposable eschmann-style bougie, commonly used to guide the endotracheal tube during difficult intubations. technique consisted in blunt dissection until the parietal pleura is opened. thoracostomy tube was preloaded onto the bougie and bougie was advanced alongside the finger, with apical or caudal direction after entering the chest cavity, depending on the type of pleural effusion. thoracostomy tube was then advanced forward utilizing a seldinger technique. the primary end point was optimal position of the chest tube. the tube position was blindly assessed on standard chest x-ray. in pneumothorax, optimal position was apical (above the aortic arch), and in hemothorax or mixed-effusion it was basal ( cm above the diaphragm or lower). results: a total of patients were enrolled (bougie-assistedn = + conventional-n = ). chest tubes were optimally position in ( %) in bougie-assisted group and ( %) in conventional group, or . , ic % = [ . - . ], p < . . efficacy of chest drainage (defined on chest x-ray as the absence of visible pleural line for pneumothorax and as a clear costophrenic angle for hemothorax) was assessed in ( %) in bougie-assisted group and in ( %) in conventional group, or . , ic % = [ . - . ], p < . . average procedure time was s ( % ci - s) for bougieassisted group and s ( % ci - s) for conventional group, p < . . no severe complication was observed in both groups. conclusion: bougie-assisted chest tube insertion technique prevents chest tube malposition, is safe, effective and shortens procedure time for the post traumatic pleural effusion drainage. introduction: infectious complications determine the prognosis of burned patients. however, the emergence of bacterial resistance to antibiotics threatens treatment efficacy, which is due to an inadequate antibiotic consumption inqualitative and quantitative terms. the objective of this study was to describe the profil of consumptionand susceptibility to antibiotics. and, to explore the predictive factors for theemergence of mrb in the service of burns and plastic surgery. patients and methods: it is a retrospective study including severe burnedpatients hospitalized for years in the plastic surgery department of theuniversity hospital ibn rochd from january to december . bacterialecology was described, and the distribution of the seeds by group, by species andby period of time was detailed. the ddd jh (daily defined dosage reportedin days of hospitalization) was used to assess the consumption of antibiotics. p correlation coefficients were calculated to explore the association betweenconsumption of antibiotics and the emergence of the bmr (multiresistantbacteria), and identified predictors of this emergence. results: on samples taken, bacterial and fungal strains were identified, with a predominance of p. aeruginosa ( . %), a. baumani i ( %) and s. aureu s ( %), the number of strains increased with the duration of the stay reaching itsmaximum from days in hospital. the ceftazidine ( . ddd dh), imipenem ( . ddd dh), and amikacin ( . ddd dh) were themost used antibiotics during our study, also + the profile of consumption increasedbetween and . bmr were isolated + the eblse were at the top ( . %) follow up of thecrpa ( . %), followed by the irpa ( . %) follow-up of the crab ( . %) then the irab ( . %) and finally the mrsa with a portion of . %. the profile of bacterial resistance has varied significantly for severalantibiotics bacteria pairs. conclusion: it remains difficult to show correlations between antibioticconsumption and bacterial resistance. however, these data are particularly usefulin the epidemiological surveillance of bacteria to better guide probabilisticantibiotic therapy. introduction: eclampsia is a rare but serious threat to maternal and fetal well-being. the aim of this study was to assess the incidence of eclampsia and its morbidity and mortality. patients and methods: we conducted a retrospective survey in a third level tunisian university teaching hospital from january to december . we included all patients with the diagnosis of eclampsia. results: in study period deliveries were registered. women with eclampsia were identified hence the incidence of eclampsia was . per deliveries. the median gestational age at the time of eclampsia was weeks. no maternal deaths due to eclampsia were recorded. the delivery mode was caesarean section in % of eclamptic patients. the recurrence of eclampsia despite magnesium sulfate prevention was observed in % of patients. severe complications of eclampsia were recorded in . % of patients- posterior reversible encephalopathy syndrome, acute pulmonary edema, and hellp syndrome. . % of new born were preterm. there were stillbirths and neonatal deaths. conclusion: the incidence of eclampsia was very high probably due to center effect. it's essential to raise awareness among mothers in the community regarding early signs and symptoms of preeclampsia eclampsia and to design a better tracking system for antenatal care program. introduction: to monitor maternal mortality which is an indicator of the quality of obstetrical care and anesthesia resuscitation, our country worked to set up several programs targeting maternal and child health. the aim of this work was-to evaluate the maternal mortality rate in our department and its evolution. to identify the cause of death and classify it depending on whether it is preventable or not. to spot the deficiencies either in the care management or the organization of the care system. to propose ways to improve our care and to fill the failures. patients and methods: it was a retrospective study about maternal death, performed at the department of gynecology and obstetrics, over a -year period (from to ) , that have reported cases of maternal death according to the world health organization definition. results: the maternal mortality rate (mmr) was . for every , live births. the average age of our patients was . years. the main risk factors for maternal mortality are unfavorable socioeconomic conditions, high-risk pregnancies, multiparity, primiparity and a poor follow-up of the pregnancy. the main causes of maternal death are represented by direct obstetric causes ( %) allocated as followspostpartum hemorrhage ( %), pregnancy toxemia ( %), acute fat hepatic steatosis ( %), infection ( %) and complications of anesthesia ( %). indirect obstetric causes were found in % of deaths. death was considered avoidable in . % of cases. conclusion: at the end of this work, we were able to pull several recommendations in order to reduce m.m.r. health education. facilitate access to care for the parturient, improve care and conditions of childbirth. continuous training of the medical and paramedical staff. introduction: mechanical ventilation can help improve the prognosis of sepsis. while adequate delivery of oxygen to tissue is crucial, hyperoxemia may be deleterious. invasive out-of-hospital ventilation is often promptly performed in life-threatening emergencies. we propose to determine whether the arterial oxygen pressure (pao ) at intensive care unit (icu) admission affects mortality at day (d ) in patients with septic shock subjected to mechanical out-of-hospital ventilation. patients and methods: we performed a monocentric retrospective observational study on patients with septic shock admitted to the icu. pao was measured at icu admission in patients subjected to invasive ventilation before any hospital admission. the primary outcome was mortality at day (d ). results: forty-nine ( %) patients with septic shock were mechanically ventilated before any hospital admission and transferred to the icu. the mean pao at icu admission was ± and ± mmhg for alive and deceased patients at d , respectively. pao was significantly associated with mortality at d (p = . ). using a roc curve, the corresponding auc was . [ . - . ]. for a pao > mmhg, the or for mortality at d was . [ . - . ] (p = . ), whereas for a pao < mmhg, the or was . [ . - . ] (p = . ). conclusion: in this study, we report a significant association between hyperoxemia at icu admission and mortality at d in patients with septic shock subjected to pre-hospital invasive mechanical ventilation. the adjustment of the pao is a crucial prognosis factor in patients with septic shock subjected to invasive out-of-hospital ventilation to avoid the toxic effects of hyperoxemia. however, blood gazometry is hard to get in a prehospital setting. consequently, alternative and feasible measures are needed, such as pulse oximetry, to improve the management of prehospital invasive ventilation. introduction: nowadays, benefit of enhanced ct-scan in positive diagnosis of acute pulmonary embolism (pe) is well established. it also allows evaluation of pe's burden on the right heart and shows several signs of acute cor pulmonale (acp). objectives -we aimed to assess benefits of control ct-scan h after thrombolysis in acute pe. patients and methods: we retrospectively enrolled patients with confirmed pe whom have been thrombolysed between january and august and controled with an enhanced ct-scan h after thrombolysis. assessement criteria were: qanadli obstruction index; signs of acp-right ventricle diameter left ventricle diameter (rvd lvd) and paradoxical interventricular septum (ivs). non inclusion criteria were: lack of initial or control ct-scan. results: during the study period ( years and months) we admitted patients from whom patients had acute pe ( . %). very severe patients that were thrombolysed as rescue therapy without initial ctscan and those who died before control ct-scan were not included. we enrolled patients-high risk mortality pe (n = , . %) and intermediate high risk pe (n = , . %). mean age was years and sex-ratio was . . at admission, mean severity scores were . ± . for saps ii and . ± . for apache ii. evolution criteria are listed in table . conclusion: control ct-scan is highly useful h after thrombolysis. it allows evaluation of response to pharmacological thrombolysis of acute pe and shows significative resolution of arterial obstruction degree and signs of acp. in december , after cancellation of the budget for a christmas tree, the nurses and caregivers of the night team spontaneously made and hung christmas decorations in our intensive care unit to make patients and their families feel better. the context was difficult with controversies around secularity. the town of paray le monial had been forced to remove a nativity scene and the city of melun had been criticized for setting one up. so we found it important to assess the perception of the approach by patients and relatives. patients and methods: decorations -hand-colored patterns about christmas theme printed on a paper decorations brought by the staff or already possessed by the unit-christmas balls, garlands, silver stardecorations made with service equipment-christmas tree consisting of inflated non-sterile gloves, cardboard, figurative nativity scene without a recognizable figure in a cardboard box with cotton, bed sheet to simulate snow. evaluation -all visitors and conscious patients received an anonymous single choice questionnaire with numerical scale and free fields from december th to december st, . results: answers were received, including-no negative opinion. neutral answer by a person who had not noticed the decorations. positive or extremely positive opinions. no answer without data. the comments pointed out the originality, the good idea, the warm comforting side. some asked for more decorations. others found them sober. the results show the good perception of the spontaneous action by the patients and their relatives. there was no negative response, particularly offend persons. however, it is possible that relatives or patients with negative opinions did not dare to express themselves. the initiative demonstrated a good cohesion of the night paramedical team, encouraging the interns and the day teams to take part in the coloring of the decorations. the initiative was initially aimed at the wellbeing of the patients and their relatives. however it has enabled an activity similar to preventing psychosocial risks among the healthcare team, allowing them to adopt a positive attitude in their approach to care. in addition, no significant costs were incurred thanks to the use of cheap materials, mainly recycled cardboard and standard quality white paper. the spontaneous decoration of our intensive care unit by the night care team was very well received by the patients, their families and their relatives. the initiative also made possible to enhance team cohesion and to value it. the associated costs were negligible. ventricular contractions. bp monitoring revealed a greater diastolic bp throughout h as well as during night-time. systolic bp higher than mmhg during sleep time was observed in % of participants. the frequency of arrhythmias and blood pressure variability are correlated with the increase in work stress and conflicts. conclusion: our results highlight the extent incidence of arrhythmia and blood pressure variability during intensive care unit night's shift probably due to the increased neuroendocrine stress response. ( %) and qrs enlargement ( %). ami was responsible for a significantly deeper coma (p < . ) but fewer seizures than clo (p = . ). three patients ( %) died. based on a univariate analysis, factors associated with death were cardiac arrest onset (p = . ), elevated plasma lactate concentration (p = . ), low arterial ph (p = . ), reduced pao fio ratio (p = . ) and prothrombine ratio (p = . ), increased aspartate aminotransferases (p = . ), alanine aminotransferases (p = . ) and serum creatinine concentration (p = . ) as well as marked catecholamine infusion rate (p = . ). the pharmacokinetic study showed significant increase in ami ( h vs. h) and clo ( h vs. h) elimination half-lives in overdose compared to pharmacological conditions, highlighting the contribution of organ failure to the delayed elimination of both toxicants. conclusion: ami and clo poisonings did not disappear and are still responsible for significant morbidities and mortality. ami was responsible for deeper coma with fewer seizures in comparison to clo. ami and clo elimination half-lives were significantly prolonged in overdose due to organ failure. introduction: severe poisonings and fatalities have been attributed to buprenorphine (bup) despite its ceiling respiratory effects, mainly if abused in co-ingestion with benzodiazepines. we previously showed that diazepam (dzp) bup combination induces severe respiratory depression in the rat, while each drug by itself does not. the objective of this study was to investigate the mechanisms involved in this drug-drug interaction using c-bup pet imaging and diaphragmatic electromyography in the sprague-dawley rat. patients and methods: c-bup was administered intravenously, mg kg unlabeled bup intraperitoneally and mg kg dzp subcutaneously. pet acquisition started with c-bup pet injection, min after dzp or its vehicle (veh + n = group) administration. suv normalized time activity curves (tacs) were generated and c-bup binding potential [bpnd, i.e. the ratio of the total receptor density (bmax) on the equilibrium dissociation constant (kd)] were modeled in different brain regions using a simplified reference tissue model with cerebellum as reference region. dem, implanted under anesthesia days before the experiment, was recorded during min in rats receiving veh veh, dzp veh, veh bup or dzp bup (n = group). after filtering and half-wave rectification, the first min auc of diaphragm contraction and workload were determined and compared between the groups. results: tacs and c-bup bpnd were not different between the dzp bup and the veh bup groups in all studied brain regions. diaphragm contraction was significantly increased in the veh bup group in comparison to the dzp bup group (p < . ). diaphragm workload was significantly increased in the veh bup group in comparison to the dzp veh and the dzp bup group (p < . and p < . respectively). discussion: dzp did not affect the c-bup brain distribution and brain binding suggesting that dzp does not affect bup transport across the blood brain barrier and bup receptors density affinity. bup administration induced an increase in diaphragm contraction and workload. this increase was inhibited in the presence of dzp suggesting that dzp bup combination-induced respiratory depression is mostly related to dzp. conclusion: respiratory depression related to dzp bup combination results from a pharmacodynamic drug-drug interaction. introduction: since the banning of dextropropoxyphene from the market, overdoses and fatalities attributed to tramadol, a who step- opioid analgesic, have increased markedly. tramadol overdose results not only in central nervous system (cns) depression attributed to its opioid properties but also in seizures, possibly related to nonopioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced cns toxicity. our objective was to investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose. patients and methods: sprague-dawley rats overdosed with mg kg intraperitoneal (ip) tramadol were randomized into four groups to receive solvent (control group), diazepam ( . mg kg ip), naloxone ( mg kg intravenous bolus followed by mg kg h infusion) and diazepam naloxone combination. sedation depth, temperature, number of seizures and intensity, whole-body plethysmography parameters and electroencephalography activity were measured. for each parameter, we compared the areas under the curves using mann-whitney tests for two-by-two comparisons between the four groups. regarding the effects of treatments on seizures, comparisons were performed using two-way analysis of variance followed by multiple comparison tests using bonferroni's correction. results: naloxone reversed tramadol-induced respiratory depression (p < . ) but significantly increased seizures (p < . ) and prolonged their occurrence time. diazepam abolished seizures but significantly deepened rat sedation (p < . ) without improving ventilation. diazepam naloxone combination completely abolished seizures, significantly improved rat ventilation by reducing inspiratory time (p < . ) but did not worsen sedation. based on the eeg study, tramadol-treated rats experienced electro-clinical seizures as soon as min after the injection, characterized by spike-waves and polyspikes with progressive decreased frequencies and inter-critical phases of slow delta waves until the next crisis. after diazepam naloxone injection, eeg waveforms consisted in hz-alpha rhythms and slow-down theta rhythms of drowsiness. none of these treatments significantly modified rat temperature. conclusion: diazepam naloxone combination is the most efficient antidote to reverse tramadol-induced cns toxicity. our experimental data greatly encourage administering this combination rather than naloxone alone as first-line antidote in tramadol-poisoned patients as an alternative to tracheal intubation. introduction: rubigine ® poisoning is a medical emergency that causes a major public health problem in underdeveloped countries, as it is frequently fatal. this poisoning is rare in france, but frequent in the french overseas departments (dom). the rubigine ® , made of fluoride and used as a rust remover, is the main source of poisoning in the caribbean. in martinique, the exact incidence of this intoxication is unknown, as there is no national and regional register. it could represent up to - % of severe acute poisoning. it was not until april that, following a prefectural order on the declaration, classification, packaging and labeling of substances, the composition of rubigine ® was modified to significantly reduce the mortality induced by its ingestion. the objective of our study was to describe the clinical features and complications that can occur after ingestion of rubigine ® as well as to determine the prognostic factors of death. we conducted a retrospective study over years, from to , including all patients admitted to emergency and intensive care units of the university hospital center (martinique) for acute rubigine ® poisoning. the usual demographic and clinical data were collected and comparisons between surviving and deceased patients were performed using a univariate analysis. results: fifty-five patients (mean age- years ( - ) + sex ratio male female- , ) were hospitalized at the university hospital of martinique. one-quarter of patients had no significant history. the average length of stay was . days ( - ). forty percent of patients experienced hypocalcaemia after initial intravenous calcium supplementation. complications included acute respiratory failure requiring invasive mechanical ventilation ( % of patients, duration of ventilation- . days, ( - )), renal failure ( %, of which % required extrarenal treatment, hemodynamic failure ( %), hepatic failure ( %), coagulation failure ( %), neurological failure ( %) and multi-visceral failure ( . %). three patients presented cardiogenic refractory shock requiring va ecmo ( . %) and another patient with digestive perforation ( . %). the mortality was . %, allowing the identification of prognostic factors of death. conclusion: rubigine ® poisoning is responsible for significant morbidity and mortality, despite optimal management. however, its incidence seems to have decreased sharply in recent years thanks to the strong mobilization and awareness of the population following the implementation of an information system by the university hospital 's clinical toxicology and toxico-vigilance unit, and different preventive measures introduced by the health authorities. introduction: since dextropropoxyphene withdrawal from the market, overdoses and fatalities attributed to tramadol, a who step- opioid analgesic drug, have increased markedly. besides central nervous system depression, tramadol overdose may result in seizures, usually included in the related serotonin syndrome. however, the serotoninergic mechanism of tramadol-induced seizures has been recently questioned. we investigated the effects of various specific pretreatments on tramadol-induced seizure onset and alterations in brain monoamines in the rat. patients and methods: sprague-dawley rats were randomized into five groups (n = group) to be pretreated with various agonists antagonists before receiving mg kg tramadol intraperitoneally- . mg kg ip diazepam + mg kg iv bolus followed by mg kg h infusion naloxone + mg kg ip cyproheptadine, and mg kg ip fexofenadine. seizure severity was graded according to the modified racine score ( ). we measured neurotransmitter concentrations in the frontal cortex using high performance liquid chromatography coupled to flurorimetry or radioenzymatic assay, as required. we used positron emission tomography-computed tomography to investigate interactions of tramadol with gaba-a receptors. the effects of treatments on seizures were compared using two-way analysis of variance followed by multiple comparison tests with bonferroni's correction. the areas under the curves of the effects on monoamine concentrations and the binding potentials in the pet-imaging study were compared two-by-two using mann-whitney u tests. results: diazepam abolished tramadol-induced seizures, by contrast to naloxone, cyproheptadine and fexofenadine pretreatments. interestingly, despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < . ), histamine (p < . ), dopamine (p < . ) and norepinephrine (p < . ) while no significant modifications were observed with the other tested pretreatments. based on positron emission tomography imaging using c-flumazenil fixation in the rat brain, we demonstrated molecular interaction between tramadol and γ-aminobutyric acid (gaba)-a receptors not related to a competitive mechanism between tramadol and flumazenil on the benzodiazepine binding site. our findings clearly ruled out the involvement of serotoninergic, opioidergic, histaminergic, dopaminergic and norepinephrinergic pathways in tramadol-induced seizures while strongly suggested tramadolinduced specific allosteric change in gabaa receptors that could contribute to seizures onset in overdose. conclusion: tramadol-induced seizures in overdose are mainly related to the gabaergic pathway. introduction: heparin-induced thrombocytopenia (hit) is a serious iatrogenic complication of heparinic treatments. the diagnosis of hit is difficult in the resuscitation environment because thrombocytopenia is a frequent and multifactorial phenomenon. the aim of this work was to study the clinical and biological presentation of patients with hit and the consequences attributable to hit on the evolution of patients in terms of morbidity and mortality and to develop a diagnostic strategy for hit for resuscitation patients. this was a retrospective, monocentric, descriptive and evaluative study conducted in our intensive care unit (icu) over a period of years months. an anti-pf antibody test was performed in patients who developed thrombocytopenia or a % drop in their initial platelet kinetics and the clinical picture. results: the incidence of hit was . % in patients hospitalized in icu. the clinicobiological severity scores, the reasons for admission to resuscitation were similar in both groups (hit+ and hit−) as well as the characteristics of the heparins used. the time of occurrence of thrombocytopenia was similar in the two groups. the diagnosis of hit was more often the only plausible diagnosis in the hit+ group. the t's score was significantly higher in the hit+ group. the evolution of the platelet count was similar in the two groups, in the decay phases as well as in the recuperation phase. hit+ patients showed significantly more thrombosis than hit− patients. there was no significant difference between the transfusion needs of hit+ and hit− patients. mortality was identical in both groups, as was the length of stay in icu. conclusion: hit is a rare disease. there was no evidence of a predisposing factor for the occurrence of the disease in a uniform resuscitation population. the diagnosis of hit is based on a cluster of arguments and not on an isolated event. biological tools are indispensable, in a complementary way to the clinical picture. pulmonary embolism in patients with sickle cell disease in intensive care unit: a challenging diagnosis jamoussi amira , zayet souheil , merhebene takoua results: during the study period, a total of patients with scd were admitted. among them, presented with respiratory distress and chest pain and then benefited first of trans-thoracic echocardiography that often showed right ventricle dilation and systolic pap > mmhg (n = ). all the patients underwent enhanced ct-scan and the diagnosis of pe was finally retained in cases ( . %) and hence colliged. the average age was . years ± . [ - years] with a sexratio = . the mean of apach ii score was . scd were diagnosed at the age of . years ± . [ - years] with a regular follow up in %. the reason for admission was acute respiratory failure in all cases. patients had clinical symptoms of pneumonia: pleuritic chest pain (n = ), dyspnea (n = ) and fever (n = ). all patients had a chest x-ray showing an alveolo-interstitial syndrome in cases ( . %) and an associated pneumonia in cases ( introduction: acute chest syndrome (acs) is the most severe complication of sickle cell disease and its evolution is unpredictable. acute pulmonary hypertension (ph) in acs is associated with an increased mortality, but its mechanism remains poorly known. our hypothesis is that acute ph is associated with a biological state of hypercoagulability in acs. in a prospective single center study, all consecutive scd patients with acs admitted to the intensive care unit (icu) of tenon hospital were included. specialized haemostasis dosages were performed on icu admission. a trans-thoracic echocardiogram was also performed on admission, and was repeated at steady state. results: among patients with acs, had a trans-thoracic echocardiogram and had a high echocardiographic probability of acute ph, including patient with bilateral pulmonary embolism and patient who developed multiple organ failure and died. there were no significant clinical, biological or radiological differences between patients with a low-intermediate probability of acute ph and those with a high probability of acute ph+ their evolution was similar. the exploration of haemostasis did not show between-group differences, regarding each parameter of haemostasis. however, when using a hierarchical cluster analysis, distinct profiles of coagulation were evidenced, defining biological classes. the subset of patients with a high echocardiographic probability of acute ph was more frequent in biological classes and which corresponded to hypercoagulability states. acute ph was transient in patients (n = ) with a repeated echocardiography at steady state. conclusion: acute ph may likely occur in patients with acs and a biological condition of hypercoagulability. further studies are needed to confirm these findings. gorham julie were the two independent predictors of survival after hospital discharge. in lung cancer patients admitted into the icu, the mgps is an independent predictor of survival after hospital discharge but not for mortality during icu stay. this inflammatory score could therefore be used as a long-term prognostic marker in this population of patients and would be more reflective of cancer, than reflecting the acute complication leading to icu admission. prospective and multicentric studies must be carried out to validate these results. introduction: recombinant active factor vii is a pro-hemostatic treatment used in obstetric haemorrhage, but no study has made it possible to specify its exact place in the decision algorithm. the objective of our work is to evaluate the efficacy and the benefit risk ratio of recombinant factor viia in the treatment of severe postpartum hemorrhage. we conducted a prospective study at the ibn jazzar university hospital in kairouan during the period from january , to december , . in total, we collected cases of recombinant factor viia in one postpartum haemorrhage. results: the mean age of our patients was + . years. the rate of childbirth was . %. the caesarean was the mode of delivery chosen for patients. the causes of postpartum haemorrhage in our series were-uterine atony in cases, uterine rupture and cervicouterine tear cases each, retroplacental hematoma and placenta accreta cases for each two and placenta praevia in cases. our patients were treated in an intensive care unit and the average hospital stay was . days. sulprostone was reported in cases ( . %), and all patients received a massive transfusion. the average time to administer rfviia was h min. the mean dose of factor vila recombinant was . ± . μg kg. five patients received a single dose, patients received a second injection and patients received doses. clinical efficacy-after a single injection, clinical efficacy with reduction in bleeding was observed in patients, i.e. %. the most frequent complication was insufficiencyrenal in cases including requiring hemodialysis, civd in cases, oap in cases, a multivisceral failure in cases, a septic shock in case and a mesenteric infarction in case. the progression was favorable in patients, while patients died ( . %). conclusion: it is important that new studies be carried out and shared experiences around the world on this drug appear to be effective and prevent invasive actions in the therapeutic arsenal of postpartum heamorrhage. introduction: post-partum haemorrhage (pph) is a life-threatening complication and remains a leading cause of maternal morbidity worldwide. the woman trial* estabished that early administration of tranexamic acid (ta) reduces mortality due to the bleeding in women with pph. our study purpose was to determine the effects of early administration of ta and fibrinogen concentrate on death, hysterectomy and transfusion in women with severe pph. patients and methods: this retrospective, monocentric study was performed in a third level tunisian hospital providing healthcare for more than pregnant women per year. were included in this study women with diagnosis of severe post partum haemorrhage after a vaginal or caesarean delivery from to . patients who received ta and fibrinogen concentrate were assessed in group (g ) and who not in group (g ). results: the incidence of severe pph was / deliveries. women were retained for data analysis g (n = ), g (n = ). anthropomorphic and obstetrics characteristics were not significantly different between the two groups. there was a significant difference between the two groups regarding to transfused units of red blood cells however, no difference in term of the use of frozen plasma and platelets concentrates was observed. perioperative hemoglobin nadir was significantly higher in g . the frequency of hysterectomy and pelvic packing were higher in g (table ) . no thromboembolic events and no haemorrhage related mortality were observed in the two groups. conclusion: in this retrospective study, early administration of tranexamic acid and fibrinogen reduces risk of hysterectomy transfusion. these encouraging results strongly support the need for a large, international, double-blind study to investigate the potential of the association "ta-fibrinogen concentrate" to reduce maternal haemorrhage related morbidity and mortality. introduction: immunodeficiency, acquired or congenital, is the first comorbidity associated with poor outcome in pediatric patients with acute respiratory distress syndrome (ards). the aim of this study was to describe outcome of pediatric patient with hematologic disease hospitalized in our intensive care unit for respiratory failure and to investigate the clinical variables associated with mortality. patients and methods: it was a retrospective monocentric descriptive study including all immunodeficient pediatric patient (malignant hemopathy, congenital immunodeficiency, bone marrow transplanta-tion…) from hematology hospitalized in our beds pediatric intensive care unit with the diagnosis of respiratory failure between january and february . results: fifty one patients were included corresponding to admissions. nighty percent of the patients met criteria for pediatric ards- % were severe, % moderate and % mild. extracorporeal circulation (ecc) was needed for patients. global mortality rate at picu discharge was %. twenty four patients ( %) received noninvasive ventilation (niv). height of them ( %) did not need invasive mechanical ventilation (imv). in patients who received imv, mortality rate was significantly higher if patients received before niv ( vs. %) p = . . all patients who needed imv after more than h of niv died (n = ). mortality was higher in children with griffon versus host disease ( vs. % p = . ). mortality of patients receiving ecc and renal replacement therapy (rtt) was respectively and %. conclusion: in our study, most of the patients hospitalized for respiratory failure met criteria for pediatric ards. if niv decrease imv requirement, it could be associated with higher mortality rate in case of failure. this result support recent recommendation that immunodeficiency is not a sufficient criteria to delayed imv. . flow and airway pressure were recorded at the asl inlet and mouth pressure into the manikin mouth. we defined "device driving pressure" as the peak mouth pressure minus the tele-expiratory mouth pressure. continuous data are reported as mean ± sd. results: as compared to the oxygen mask, vt increased significantly with m-niv and h-niv whatever the simulated respiratory effort ( ± and ± vs. ± ml respectively with the moderate simulated effort, p < . ; fig. ). hfnc and cpap were associated with a slight but non-significant decrease in vt as compared to the oxygen mask. overall, for a given respiratory effort, vt was influenced by the "device driving pressure", which tended to decrease when using hfnc and cpap and markedly increased with m-niv as compared to the oxygen mask. therefore, vt in m-niv with a simulated low effort was significantly higher than vt in cpap and hfnc with a simulated moderate effort ( ± ml, ± ml, and ± ml respectively, p = . for both comparisons). conclusion: in our bench model, the vt value was significantly influenced by the noninvasive ventilatory device. niv was invariably associated with significantly higher vt than with other devices, even when dividing by two the simulated inspiratory effort during niv. introduction: in icu, intubation is a high risk procedure associated with high morbidity. despite procedure's improvement with systematic application of fluid loading, early use of vasopressors and checklist use, morbidity remains high. several recent trials has been conducted with different metrics choose as primary outcome. however any evidence exists to choose one more than another: time to intubation, first pass success, difficult intubation. first pass success sine hypoxia and hypotension (dash- a) has been highlighted recently and choose by the game program without any scientific evaluation. we conducted a post hoc analysis of the randomized clinical trial macgrath mac video laryngoscope or macintosh laryngoscope for intubation in the intensive care unit (macman) to determine the best metric to choose for primary outcome for the next intubation studies in icu. patients and methods: macman was a multicentre, open-label, randomized controlled superiority trial. consecutive patients requiring intubation were randomly allocated to either the mcgrath mac videolaryngoscope or the macintosh laryngoscope, with stratification by centre and operator experience. an only inclusion criterion was-"patients must be admitted to an icu and require mechanical ventilation through an endotracheal tube". patients were excluded if-contraindication to orotracheal intubation (e.g., unstable spinal lesion) + insufficient time to include and randomize the patient (e.g., because of cardiac arrest) + age < years + pregnant or breastfeeding woman + correctional facility inmate + patient under guardianship + patient without health insurance + refusal of the patient or next of kin to participate in the study + previous enrolment in a clinical randomized trial with intubation as the primary end point (including previous inclusion in the present trial). post-hoc analysis was performed to assess association and prediction of life threatening complication (mild to moderate, severe, mild to severe) by different metric existing-time to intubation, first pass success, difficult intubation, first pass success sine hypoxia and hypotension. each metric was compared with another one. area under curve was built for every metric and all metrics were then compared. results: dash- a was superior to all others metrics included in the analysis for prediction of life threatning complications (all p < . ). failure of first pass conclusion: all metrics are not equal to predict severe life threatening complications during intubation in the icu. in this context, we recommend adoption of definitive airway sine hypoxia or hypotension at first attempt (dash- a) as primary outcome for intubation studies in the icu or as metric indicator tracked in quality improvement program. benbernou soumia introduction: introductionacute respiratory failure (arf) is a common cause of emergency use and one of the major reasons for admission to intensive care unit. it associates a vital risk imposing immediate symptomatic treatments and an etiological approach. [ ] among the etiologies of the arf, acute lung edema (ale), decompensation of chronic obstructive pulmonary disease (copd), chest trauma and pneumonia are the most frequent @it is a life-threatening pathology with a high incidence of mortality, since mortality is reported to be - % [ , ] for arf secondary to cardiogenic ale. the prevalence of arf in algeria remains unknown + the tahina study showed that respiratory diseases were the leading cause of consultation in the hospital [ ] . the the objective of this study is to estimate the frequency of use of the niv and to determine the associated factors of failure of the niv for the adult patients hospitalized for arf in the emergency department of oran hospital from january to november . prevalence of copd was found in the . % of tobacco subjects [ ] . the number of patients hospitalized for chest trauma continues to increase, resulting in an increase in the number of patients admitted for arf secondary to chest trauma. patients and methods: this is an observational and exhaustive study during the month of november, from the files of patients. the population-all subjects over years hospitalized for an arf at the reception and resuscitation units of the emergency department of oran hospital from january to november . results: ninety-seven patients were hospitalized for arf during this period. niv was used for patients. patients were acute lung edema. univariate analysis showed that spo was the only failure factor in this series. the failure rate of this technique was . %. niv is a technique that should be used more in the emergency rooms, which would make it possible to use less intubation specially in indications where the level of proof in the literature is important. demographic characteristics, etiology of exacerbation, comorbidities, the sapsii score, arterial blood gases at admission, respiratory, hemodynamic and neurological parameters, use of noninvasive or invasive ventilation, nosocomial infection, duration of niv, length of stay and mortality. results: during period study patients ( % women with a sapsii score ± ) were included. the etiology of exacerbation was bronchitis in % of cases and pneumonia in %. only patients have niv at home and patients have oxygen. pseudomonas aeruginosa was isolated in cases. twenty percent of the patients had developed a nosocomial infection, acinetobacter baumanii and pseudomonas aeruginosa were isolated in and % respectively. niv was used in patients at admission and the rate of niv failure was %. the duration of mechanical ventilation was ± days and the length of stay was ± days. the mortality was %. niv and oxygen at home were prescribed for patients. in univariate analysis survivors and non-survivors were comparable regarding baseline and clinical characteristics. nosocomial infections ( vs. %), and spassii score were significantly more elevated in non-survivors. in emergency department, the management of hypercapnic acute respiratory failure with hfo is limited. hypercapnia and acidosis remain moderate. patients are old with comorbidities. the mortality rate is high but expected given the number of limitation of active therapy. hfo appears to be effective for a majority of patients, but half of them required niv too. the niv hfo association seems an interesting option. but our methodology is perfectible and would require a randomized control tria. severe chronic obstructive pulmonary disease with chronic respiratory failure in intensive care unit: mortality and prognostic factors arnout chloé , faure morgane , novy emmanuel chu nancy, nancy, france correspondence: arnout chloé -arnout.chloe@gmail.com introduction: last decades, the number of patient with chronic respiratory failure due to chronic obstructive pulmonary disease (copd) admitted in intensive care unit (icu) increased. data about their real prognosis in the icu are lacking. the objective of this study was to evaluate mortality rate at months and to identify prognostic factors of copd patients with chronic respiratory failure, treated with long term oxygen therapy (ltot), admitted in icu. patients and methods: a retrospective cohort study was conducted in the french university hospital of nancy during years - on all copd patients treated with ltot admitted in icu. only the first admission was analysed. patients were included if they had spirometry, blood gas and oxygen flow in the year before admission in icu. other causes of chronic respiratory failure, and patients with tracheostomy before icu admission were excluded of the cohort. hospitalizations were selected using the international classification of diseases, th revision (icd- ). results: one hundred and thirteen patients were included, ( %) died in the first months after icu admission. mortality rate in icu was %. severity of copd was-mean bode score ± . , number of exacerbation per year requiring hospitalization ± . . ltot was used for . ± . years. acute respiratory failure was the main frequent cause- % pneumonia, % acute exacerbation of copd, % acute lung oedema. the sequential organ failure assessment score within the first h of icu admission was ± . need for mechanical ventilation was noted in % of cases and was associated to mortality with an odds ratio of . (ci % [ . - ] p = . ). in presence of other organ failure, mortality rate tends to increase. patients with median pao fio ratio > on first blood gas had a reduced risk of death (or . + ci % [ . - . ], p = . ). conclusion: this is the first study to assess mortality at month of patients with severe copd requiring ltot admitted in icu. severity of hypoxemia and use of mechanical ventilation are two prognosis factor of mortality. the addition of another organ failure seems to increase the mortality rate. severity of the chronic respiratory insufficiency less influenced short and long term outcome. this data have to be included in the global decision to admit a copd patient with ltot in icu. introduction: the remarkable progress in the outpatient care of the asthmatic patient (development and access to inhaled drugs) has made the admission of these patients exceptional in the icu. we have noticed a recent upsurge in asthmatic afmissions in the icu, and are investigating whether this fact was related to modifiable factors (access to adapted drugs) or an increase in the severity of the disease. patients and methods: retrospective, observational, three-center study conducted in three tunisian medical icu from january to july, . were included all consecutive patients admitted for severe acute asthma in three icus. were assessed-patient's demographic characteristics, asthma severity and its actual control based on global initiative for asthma classification (gina) , clinical characteristics of the acute episode, length of icu stay, ventilatory free days and mortality. results: out of the patients admitted within the study period, ( %) had severe acute asthma. the mean age was years (iqr - . ). sex ratio was . asthma was allergic in % with an average ancienty of . years. over all asthma was not very severe with no prior icu admission for acute severe asthma . % were mechanically ventilated at least one time. were classified severe and moderate persistant asthma respectively in . (%) and (%). . % were consideredpoorly controlled. low educational level and socio-economic status are the main determinants of poor control- % of analyzed patients didn't have a social care, and thus no accesse to prescribed anti-asthmatics + % didn't have a regular follow up and . % were jobless. when admitted to the icu- patients ( . %) needed invasive mechanical ventilation, one patient received niv. the mean length of stay was days (iqr . - . ). levels of auto peep and pic pressure at icu admission were respectively (iqr - ) and . (iqr , - . ) cm h o. mortality rate was %. this study suggests that low educational level and socioeconomic status (especially the lack of social care and joblessness) are the main determinants of poor control of asthma and may lead to the increase of rate of icu admission for severe acute asthma requiring mechanical ventilation. introduction: in emergency medicine, the boussignac system (bs) is sometimes used to administer oxygen and continuous positive airway pressure (cpap). in this case, fio value depends on the ratio between o flow and inspiratory flow (if). in some cases, the fio decreases due to the if increase. the aim of this study was to test a modified boussignac system in order to limit the fio decreases during inspiratory flow rate increases. the study was conducted on bench with bs connected to a two compartment adult lung model (dual test lung ® ) (dtl) controlled by a maquet servo i ® ventilator. three minute ventilation (mv- . . l min) with ti ttot = . were investigated. fio and mv measurements were made using an iworx ® ga gas analyzer. with a bs, two peep were analyzed- and cm h o. the bs was supplied by an o flow. in order to increase the fio , we have evaluated the addition of a t piece connected to a nebulizer at the air-room admission of a bs. the aerosol was supplied by an o flow of l min. the o flow was analyzed in continuous with a calibrated mass flow meter (red y vogtlyn ™ ). results: when mv increases, the fio decreases (p < . ). when peep increases, fio increases too (p < . ). the addition of an aerosol (o - l min) to a bs increases the fio (p < . ). however, in this last case, the gap between both fio decreases with increases mv (fig. ) . the addition of an aerosol connected to an o flow rate ( l min) at the entry of a bs limits the fio decreases during the mv increases. introduction: burned patients are at high risk of yeast colonization and thus of invasive fungal infections, particularly to candida (c.) spp., leading to an increase in morbidity and mortality. while pre-emptive antifungal therapy has improved survival, it may lead to an increase in antifungal resistance. the objectives of this work were to describe candida species distribution and to determine the antifungal susceptibility of candida isolates acquired in a burn unit. our study is a retrospective review of severely burned patients admitted to the burn unit of the ben arous traumatology and burns center with one or more positive culture sites for candida, during the -month period from may through august . a total of isolates were thus obtained. the susceptibility to antifungal drugs ( -fluorocytosine, fluconazole, ketoconazole, micronazole, itraconazole, amphotericin b) was determined using the fungitest ® broth dilution method for patients with infected normally sterile body sites or a candida colonization index superior or equal to . . since echinocandin and anidulafungine were recently introduced in tunisia, the susceptibility to these antifungal classes was tested for only one patient from our cohort. results: nasal and buccal sites were the most colonized body sites ( . % each), followed by axillary ( . %) and rectal sites ( . %) and urines ( . %). c. albicans was the predominant species ( . %), followed by c. glabrata ( . %), c. tropicalis ( . %) and c. parapsilosis ( . %). among the strains whose antifungal susceptibility was determined, majority of candida isolates were susceptible to fluconazole ( . %), which is the most frequently used molecule as a pre-emptive treatment in such cases in tunisia due to its availability and its efficiency. on the other hand, . % of the isolates were intermediate and . % were resistant to this antifungal drug, mainly c. glabrata for both groups. as for the other tested azoles, high rates of intermediate strains were noticed ( . % to itraconazole, . % to ketoconazole and . % to miconazole), mostly c. glabrata. only one strain was resistant to amphotericin b, which is not usually used in these cases due to its nephrotoxicity and the frequency of kidney failure in burned patients. our study demonstrates that c. albicans is the most frequent species in burn unit-acquired candidiasis. no major antifungal resistance was observed, apart from high rates of intermediate strains (mainly c. glabrata) to azole class antifungal drugs. introduction: infection, especially bacteremia, is a major cause of morbi-mortality in severely burned patients. mortalityrelated to bacteremia in burn patients was about % [ ] . we performed this study to determine the prevalence, the causative agents and outcomes of bacteremia in burned patients. introduction: carbapenems, the last line of therapy, are now frequently needed to treat nosocomial infections, and increasing resistance to this class of β-lactams limit antibiotic options in critically ill patients especially in burns. the objective of our study was to assess the impact of the detection of carbaménépases in optimizing treatments in burned. patients and methods: a prospective, monocentric study was carried out at the intensive care unit of burn in tunisia over months (march-august ). were included all patients who have had a carbapenemase research. the sample was carried out by rectal swab. all samples were analyzed by polymerase chain reaction (pcr) methods for presence of carbapenemase. during the study period, patients were included. the mean age was ± years. they were men and women. the average burned surface area was ± %. patients were transferred from another hospital structure in % of cases with a delay of h. % of patients had a septic complication with a delay of ± days. antibiotic treatment was empirical in cases. the therapeutic failure rate was %. results of carbame-nepases detected by pcr are detailed in table . in the group of patients pcr (+), the antibiotic treatment was changed in cases. the most association of antibiotics were-tigecycline in combination with colistin or in combination with fosfomycine and fosfomycin in combination with colistin. this leads to reduce therapeutic failure by %. conclusion: detection of carbapenemase in our study was higher ( %), allows us to identify regions with high risk of carbapenemase, improve therapeutic efficacy and strengthen infection control measures by isolation of all carbapenemase producing patient. introduction: icu-acquired bacteraemia is prevalent and poses a grave threat. providing information about the main causative bacterial agents and determination of their susceptibility to antibiotics may improve empiric therapy and early detection of emerging antimicrobial resistance. the aim of this study was to investigate the species distribution and antibiotic susceptibility of isolated strains from blood culture in burn intensive care unit during a five-year period. patients and methods: from january to december , a total of , non repetitive strains were isolated from blood cultures. incubation of blood culture vials and the detection of bacterial growth were performed by the bactec system. all isolated organisms were identified on the basis of standard microbiological techniques. antibiotic susceptibility testing was carried out by the agar disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm and guidelines. data were analyzed using the sir-system. minimum inhibitory concentrations of colistin, imipenem and vancomycin were determined using the etest ® method (biomérieux). results: of the , strains isolated, the most frequently identified species were staphylococcus aureus ( %), acinetobacter baumannii ( %), klebsiella pneumoniae ( %), and pseudomonas aeruginosa ( %). the rate of methicillin-resistant staphylococcus aureus (mrsa) was %. resistance to tigecycline and linezolid was and %, respectively. all strains were susceptible to glycopeptides. in addition, isolated acinetobacter baumanii strains showed high rates of resistant to all tested antibiotics except colistin. eighty per cent of these strains were resistant to ceftazidime and % to imipenem. resistance to rifampicin was % in , and has increased steadily to % by . similarly, high resistance rates were observed among klebsiella pneumoniae and pseudomonas aeruginosa to ceftazidime ( and % respectively), ciprofloxacin ( and %) and imipenem ( and %). conclusion: this study investigated on the local distribution patterns of causative organisms of bacteraemia in burn patients and the corresponding antimicrobial susceptibility profiles. multidrug-resistant pathogens, especially mrsa and acinetobacter baumanii, were the most frequently isolated organisms. hygiene measures and antimicrobial stewardship should be implemented to prevent the spreading of these resistant strains. introduction: pseudomonas aeruginosa is known opportunistic pathogen frequently causing serious infections in burned patients. multidrug resistance in this pathogen is increasing throughout the world and is a major problem in the management of these pathogens. analysis of serotype and resistance profile to antobiotics of p. aeruginosa help to establish a prompt control and prevention program. the aim of this study was to evaluate the frequency of antimicrobial resistance and the prevalence of pseudomonas aeruginosa serotypes isolated in the burn unit. patients and methods: during a period of years (from to ), strains of pseudomonas aeruginosa were isolated from burned patients. conventional methods were used for identification. antimicrobial susceptibility testing was performed with disk diffusion method and susceptibility data were interpreted according to breakpoints recommended by the french society of microbiology (fsm). serotypes were identified by slide agglutination test using p. aeruginosa o antisera (biorad). the imipenem-resistant strains have benefited from a research of carbapenemase production by the edta test. results: in our study period, bacterial isolates were found among which pseudomonas aeruginosa was the second most frequent bacterium isolated from burned patients ( %) after staphylococcus aureus ( %). the most frequent sites were-cutaneus infection ( %), blood culture ( %) and catheter ( %). the most prevalent serotypes were-o ( %), o ( %), o ( %), o ( %) and o ( %). the survey of antibiotic susceptibilily showed high pourcentage of resistance to the different antibiotics- % of strains were resistant to ceftazidim, % to ticarcillin, % to ciprofloxacin, % to amikacin and % to imipenem. among the imipenem resistant strains, % were metallo-beta-lactamase producers. the antibiotic to which p. aeruginosa was the most susceptible was colistin ( %). multidrugresistance was associated with o serotype in % of the cases. the global frequency of serotypes o , o and o was more than %. multidrug resistance and carbapenemase being associated with serotype o . serotyping of the strains isolated from burned patients will help to guide the first antibiotherapy. the dissemination of carbapenemases strains must be contained by implementation of timely identification, strict isolation methods and better hygienic procedures. and respiratory disorders ( . %)…). the therapeutic management was based on per operative resuscitation, organ failure treatment, probabilistic antibiotic therapy and median laparotomy surgery. the main etiologies of abdominal sepsis were-digestive perforations ( . %), purulent effusion ( %), intestinal necrosis ( %), cholecystitis ( . %). the bacteriological profile was -predominance of bgn ( . %) dominated by e. coli ( %) followed by klebsiella pneumoniae and acinetobacter baumanii ( . %), the mean duration of the hospitalization was . ± . days. the mortality rate was %. the main prognostic factors in our study in univariate analysis were-the advanced age, the diabetes, the organ failure, the increased gravity scores, the time to management, the use of catecholamines and the development of septic shock. the multivariate analysis showed a statistically significant association between the development of septic shock, the stercoral effusion, the peptic ulcer perforation, the operator and the therapeutic descalation. the abdominal sepsis is a serious affection, with great mortality. the improvement of its prognosis is based on a revision of the medical and surgical protocols, and an adapted antibiotic therapy depending on the direct examination of the samples, also of the bacterial ecology of the service. introduction: severe acute respiratory infections (sari) are common in critically ill patients. viruses can be found in immuno-competent patients. however, the main problem for viral infections is the diagnosis, isolation of the pathogen is often difficult and the symptoms not specific. the aims of this study were to describing the epidemiological characteristics of viral respiratory infections, to identify factors predictive of a poor outcome. introduction: in septic shock there are physiological changes with an increase in the volume of distribution, with implications for pharmacokinetics of antibiotics that make recommended doses potentially inadequate for target organisms with highest minimal inhibitory concentrations. to cover these bacteria, peak serum concentration (cmax) target is - pg ml. identification of predictive factors for insufficient cmax, in common practice, would make it possible to target the patients at risk in order to optimize dosage of antibiotic to be administered. objective of this study was to determine predictive factors of amikacin's cmax insufficient independently of the dosage. patients and methods: this was a retrospective study carried out between august and november in icu of our hospital. all adult patient receiving an initial injection of amikacin between and mg kg were included. clinical data collected were-amikacin dosage, body mass index (bmi), mechanical ventilation (mv), mean arterial pressure (map), use of noradrenaline and continuous hemofiltration (cvvh). biological elements were collected and for each, the last result in the h prior to admission and that at the patient's entry into icu were added to analysis. a comparison of this clinical and biological variables was made between two groups-the first one with an ineffective cmax of amikacin (< pg ml) and the second with an effective cmax of amikacin (> pg ml). results: patients were selected for statistical analysis. median dosage was . mg kg for a median cmax at . mg l. for patients, cmax was less than mg l and in patients, it was greater than mg l. there was a statistically significant relationship between a cmax greater than mg l and mv, bmi, pct measured before and after admission, albumin after admission, hemoglobinemia, hematocrit level after admission, the rate of urea after admission (table ) . a low bmi was associated with cmax < mg l. discussion: these results remain comparable to those found by taccone in , with dosages of mg kg having only % of the peaks above mg l + comparable also to montmollin's study in . conclusion: mv, bmi, pre-and post-admission pct, and albumin, hemoglobin after admission, hematocrit and urea after admission seems to be predictive criteria for insufficient amikacin's cmax independently of dosage. our study was limited to one icu, a heterogeneous recruitment, and that all samples have been taken at the right time. introduction: this study aimed to assess whether augmented renal clearance (arc) impacts negatively on ceftriaxone pharmacokinetic pharmacodynamics (pk/pd) target attainment in critically ill patients receiving g day by intermittent infusion. patients and methods: over an -month period, all critically ill patients treated by ceftriaxone for a first episode of sepsis without renal impairment were eligible. during the first days of antimicrobial therapy, every patient underwent -hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at trough concentrations. the main outcome investigated in this study was the rate of empirical target non-attainment using a theoretical target mic of mg/l. results: over the study period, patients were included ( samples analyzed for therapeutic drug monitoring). the rate of pk/pd target non-attainment was %, with a strong association with crcl (p < . ) ( table ). there was no statistical association between pk/ pd target non-attainment and therapeutic failure. conclusion: when targeting %ft > mic of the less susceptible pathogens, patients with crcl > ml/min are at risk of subexposure in ceftriaxone ( g day). these data emphasize the need of therapeutic drug monitoring in patients with arc, especially when targeting less susceptible pathogens or surgical infections with limited penetration of antimicrobial agents. introduction: the septic shock is a major concern of the intensive care unit in the world because of its frequency and especially of its mortality which remains high in spite of the progress made in the optimizing care. the aim of our work is to analyze the prognosis factors related to death among patients with septic shock in the icu of the military hospital avicenna of marrakesh, and to focus on the physiopathological and therapeutic data of the septic shock in the light of last acquisitions in this field. patients and methods: we proceed to a prospective study including all patients with septic shock at admission to icu or secondary, over a -year period (january -december ). prognosis factors related to death in patients with septic shock were studied in univariate and multivariate analysis. results: eighty-six cases of septic shock were collected from icu admissions, the incidence is . %, the mean age was ± . . the sites of infection most often involved were the abdomen and lung ( %), there was a predominance of gram-negative bacilli, the number of organ failure is in average . ± . . the overall mortality was . %. prognosis factors related to mortality retained after logistic regression are cardiovascular organ failure followed by neurological. indeed, the number of patients with or more failures was ( %) in the group of patients who died. as the second factor influencing the high mortality found severity score . ± . , age is also considered a prognosis factor since of patients were over years. the average age of the deceased was ± years versus ± years in survivors (p < . ), yet the mortality according to the infectious agent was not found as factor influencing mortality (p = . ). conclusion: septic shock is a frequent reason for hospitalization in icu. the improvement of prognosis requires an early and adapted management of sepsis as well as increases efforts for control and prevention of nosocomial infection. introduction: vitamin d deficiency is common in critically-ill patients. in addition to its role in the regulation of phosphor-calcic metabolism, vitamin d is of paramount importance for the immune system. the aim of the current study is to assess the prognostic value of vitamin d deficiency in patients with septic shock. patients and methods: retrospective study conducted over months. all the adult patients with septic shock and vitamin d level screening performed within the first h of admission were included in the study. we excluded patients with chronic kidney disease and those receiving vitamin d supply. two groups were compared: those with a serum vitamin d level < ng/ml (g ) and those with higher level (g introduction: since immunity plays a central role in neoplasms surveillance, it is likely that sepsis induced immune dysfunctions may impact on the underlying malignancy. we developed a research project investigating the reciprocal relationships between bacterial sepsis and cancer. we reported that sepsis-induced immune suppression promoted tumor growth in post-septic mice inoculated with cancer. in a reverse cancer-then-sepsis model we observed that sepsis may conversely inhibit tumor growth. this study aimed at investigating the cellular and molecular mechanisms of sepsis-induced tumor inhibition, and most especially the role of monocytes macrophages and toll-like receptor (tlr) signaling. patients and methods: we used c bl j wild-type (wt), tlr -/-, tlr -/-and myd -/-mice. mice were first subjected to tumor inoculation by subcutaneous injection of mca fibrosarcoma cells. fourteen days after, mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (clp). controls were cancer mice subjected to sham surgery. alternatively, cancer mice were subjected to an i.p. challenge with tlr agonist (lps or heat-killed staphylococcus aureus (hksa)). the distribution of tumor-associated immune cells was assessed by facs at days and following surgery. the activation status of tumorinfiltrating monocytes macrophages was assessed by facs (mhcii, cd , cd , pdl , pd ). f / + cells were purified by facs and we assessed cytokines production (rt-qpcr) and bacteria phagocytosis. we confirmed polymicrobial sepsis dampens tumor growth in wt mice. a similar clp-induced tumor growth inhibition was observed in tlr -/-mice, but neither in tlr -/-nor myd -/-mice. a challenge with lps resulted in a marked anti-tumoral effect, whereas a challenge with hksa had no impact on tumor growth. tumor-infiltrating immune cells analysis retrieved monocytes/macrophages predominance with two different subsets based on f / expression (f / high and f / low). late-onset (day ) tumors from clp-operated mice displayed increased proportions of f / high. as compared to f / low cells, f / high cells displayed a more immature status with a lower expression of cd , mhcii and pdl , and a higher phagocytic activity. interestingly, f / high cells from clp-operated mice exhibited a higher phagocytic activity than those from sham-operated mice. conclusion: polymicrobial sepsis drives a potent antitumoral activity in cancer mice, which is associated with changes in the distribution and functions of tumor-associated monocytes macrophages subsets. our results converge on a critical role of tlr signaling, that should be further investigated. conclusion: post-agressive immunosuppression in icu is not specific to sepsis. in septic shock, the low counts in circulating ilc s could be explained by ilc plasticity (conversion of these cells into ilc s), by migration from the blood or by an exacerbated apoptosis. ilc s expansion, associated with a higher risk of secondary infection, could be promoted by il- , released by tissue injuries. ilc s could activate regulatory t cells via il- . these preliminary results must be confirmed on a larger cohort. they play a suppressive role in the immune system by the secretion of negative regulatory cytokines such as interleukin- or by immune cell contact inhibition. the objective of this pilot study was to develop and test a protocol to determine the breg level in septic patients. the level of breg were measured on whole blood sample by flow cytometry the first day of hospitalisation in septic patients. b cells were identified on the single-parameter expression cd combined with scatter. the breg were identified as subpopulation expressing cd /hicd hi or cd /hicd + (see fig. ). the results were expressed as percentage of the parental lineage gate and absolute value per microliter. this protocol has been optimised in order to be able to transfer technic into clinical practice. results: we include patients hospitalized in intensive care unit with severe sepsis or septic shock. the percentage of cd + cd hic-d hi was . ± . % with a mean of . ± . cells microliter. the percentage of cd + cd hicd + was . ± . % with a mean of . ± . cells microliter. we are able to measure and follow the evolution of breg during severe sepsis or septic shock. because breg could inhibit body immune function, we wish to conduct a prospective study to evaluate the correlation between breg level and the prognosis of patients with sepsis. the neutrophil/lymphocyte ratio (nlr) reflects an inflammatory state. the nlr has recently emerged as a prognostic marker in colorectal cancer patients, acute coronary syndrome and pulmonary embolism (kayrak m, heart lung circ ). the aim of this study was to assess the prognostic value of nlr in patients with septic shock. we performed a prospective observational study in septic shock icu patients within h of admission from january to july in charles nicolle hospital of tunis. exclusion criteria were age < years, pregnancy + oncohematological patients, recent blood transfusion, post-cardiac arrest and brain-death. nlr was measured soon after admission and h, h, and h after. demographic, clinical and biochemical parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of icu stay were recorded. the primary endpoint was -day mortality. results: sixty-five patients ( males, median age, . years) with septic shock were included in the study. the -day mortality was %. the median sofa score at t was points and the median igs score was points. the sources of infection were as follows: the lungs (n = ), the urinary tract (n = ), the central nervous system (n = ), the abdomen (n = ), skin and soft tissue (n = ). the parameters that were identified through univariate analysis to be associated with -day mortality were igs score, lactate level, the nlr elevation at h , h and h . median nlr levels were significantly higher in non-survivors (n = ) than survivors ( introduction: the autonomic nervous system (ans) is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of ans activity and a relation between hrv and outcome has been proposed in various types of patients. we evaluated the feasibility of a automated hrv monitoring, based on standard electrocardiography monitoring, and investigated the different parameters that should be recorded. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct ) that aims to record more than icu patients over a -years period. patients and methods: physiological tracings were recorded from the standard monitoring system (intelliview mp philips), using a dedicated network and extraction software (synapse v , ltsi inserm u ) that enables simultaneous recording of different physiological curves, at their native resolution ( hz for ecg, hz for other). raw data were subsequently stored on a dedicated local server, before anonymization and analysis. all consecutive patients were recorded for a -hours period during the -hours following icu admission. all measurements were recorded with the patient laying supine, with a ° bed head angulation. physiological recordings were associated with metadata collection by a dedicated research assistant. hrv parameters were derived from electrocardiography monitoring using kubios hrv premium ( introduction: acute cor pulmonale (acp) is a frequent complication of acute respiratory distress syndrome (ards). it occurs in % of cases and might be associated with an increased mortality rate. it is defined by a ratio of telediastolic surfaces of right ventricular (rv) on left ventricular greater than . and a septal dyskinesia. however, systolic dysfunction defined by the guidelines of the american society of echocardiography has not been well studied in ards and in particular concerning the rv free wall longitudinal strain (rv-fw-ls). the aims of the present study were to identify the prevalence of rv systolic dysfunction and acp in ards, and to evaluate the effects of inhaled nitric oxide (noi) and prone positioning. we prospectively included patients to a mild to severe ards, and proceeded to standardization of ventilation and systematic echocardiography in semirecumbent position, with noi and in prone position. interpretation of examination was blinded to the investigator. we evaluated the presence of acp, systolic dysfunction identified by classical cardiologic criteria (rv fractional area change, rv tei index, tricuspid annular plane systolic excursion, velocity of the tricuspid annular systolic motion) and also by rv-fw-ls. results: sixteen patients were included. thirty-seven percent of patients were in severe ards. the prevalence of acp was % while right ventricular systolic dysfunction was identified in . % of patients with the classic cardiologic criteria and . % with the impairment of rv-fw-ls which represented the most sensitive test for right ventricular dysfunction detection (table ) introduction: the use of extra corporeal membrane oxygenation (ecmo) is increasing. brain complications may occur, resulting in an increased morbidity and mortality. the objective of our study was to analyze the incidence of neurological complications while receiving ecmo, the risk factors, and to describe morbidity and mortality in a large cohort of patients in intensive care unit. patients and methods: this was an observational, mono-centric, -year retrospective study in patients who received ecmo. primary outcome was the occurrence of neurological complication until d after ecmo. results: one hundred and eight patients were included in the analysis. twenty-seven patients ( %) presented a neurological complication. of these, died at d . there were ischemic sequelae ( . %), intracranial haemorrhages ( . %), cerebral edema ( . %) and one other lesion ( . %). the median time before occurence of a neurological complication was days after the implementation of ecmo. multivariate analysis revealed the presence of hyperlactatemia > . mmol l, neurological deficit at the beginning of the management, as well as the history of stroke before the ecmo implementation as predictive factors of neurological complication (or . , . the incidence of neurological complications under ecmo is about % and ischemic sequelae are the most frequent. history of stroke and low cerebral flow associated with ischemia-reperfusion seem to increase the occurrence of these complications and must lead to greater vigilance in these patients. - ] . eighteen patients ( %) survived at icu discharge with a good neurological outcome. by multivariate logistic regression analysis, female sex, initial shockable rhythm, and pre-ecmo arterial blood ph ≥ . were independent predictors of survival with good neurological outcome. all of the patients presenting with cpc score of or at icu discharge had a shockable rhythm and or ph ≥ . before ecls implantation. % of the patients presenting with these criteria had a good neurological outcome at icu discharge. all of the patients presenting with non-shockable rhythm and ph < . before ecls implantation died in the icu. conclusion: about one third of the patients presenting with shockable rhythm and or ph ≥ . before ecls implantation had a good neurological outcome at icu discharge. on the contrary, all of the patients presenting with both non-shockable rhythm and ph < . before ecls implantation died in the icu. these simple parameters might help to identify cardiac arrest patients which could benefit from ecls implantation. radjou aguila introduction: the decrease of lung volume is a keystone for the management of patients under mechanical ventilation in intensive care units. this procedure has not only led to a reduction of morbimortality in ards but also in all patients mechanicaly ventilated in intensive care units as well as in major surjery. nevertheless, the incidence of high volume (vt) on morbimortality is extremely variable (about to %). our main objective is to assess the incidence of high volume ventilation (> ml/kg predicted body weight, pbw) in our hospital intensive care units. moreover we were interested in determining the risk factors of high volume ventilation. we conducted a retrospective observational study from january to march in three intensive care units of a tertiary university hospital. all patients ventilated under sedation in vac mode during the h after admission were included in the study. of the patients admissions during the period, one of them ( %) have no height mentioned in their medical file and were exluded. among the patients considered, ( . %) were ventilated with high vt (fig. ). % of patients had a positive expiratory pressure ≥ cmh o. in multivariable analysis, height (smaller) and weight (lower) are the only associated factors with a high volume ventilation (p < . and p = . , respectively). discussion: the observed incidence on high vt patients is higher than that reported in most papers in literature (jaber et al. %, hess et al. %) . nevertheless, both studies were conducted in operating room with higher vt cut-off ( ml/kg). walkey and al showed that % of patients in ards were ventilated with vt › ml/kg of pbw. moreover, the same associated factors (smaller height and lower weight) have found in the study. older studies revealed higher bmi as factor to high volume ventilation. this difference could be explained by the use of predicted body weight. conclusion: although the growing literature and the recommandations aim to reduce the lung volume between to ml/kg of pbw, still one third of the patients in intensive care units are ventilated with too high lung volume. (fig. ). with either a nc overlap on one nostril or not. results: when the mv increases, the fio decreases. when the mouth opens, the fio decreases. when the prongs are overlapping one nostril the fio decreases slightly (mean ± % in absolute value). statistical differences were found between closed and open mouth and between overlap on one nostril and not (p < . ), except between tmo and cm at two mv ( and l/min) when nc overlap on one nostril (fig. ) . conclusion: when the prongs of nc are not correctly placed in the nostrils, the fio decreases, but this impact is limited in our bench study. the impact of mv increases and mouth opening on the fio values is also important. introduction: the weaning of mechanical ventilation is an essential and delicate phase in the management of a resuscitation patient. the neurosurgical patient presents a number of specific problems, such as impaired control ventilatory control, coughing or the pharyngo-laryngeal intersection. however, it often allows short-term ventilatory withdrawal in the neurosurgical patient, probably largely by the simple fact that it authorizes the definitive cessation of sedation. the objective of the study and demonstrate the place of tracheotomy in neuro-resuscitation patients, and prevent its complications. a retrospective descriptive study of patients hospitalized in the neuro-resuscitation unit during the period january to december , of which patients benefited from surgical tracheotomy, is a frequency of % of all inpatients during this period. clinical, para-clinical, etiological, and therapeutic data were collected from hospitalization records. in a series of hospitalized patients, during the defined period, patients had surgical tracheotomy, a frequency of %, in the literature two studies or the data were extremely variable, with % in the study namen versus . % in the coplin study. of the tracheotomies, were performed by neurosurgeons, and by resuscitators at a frequency of %. the tracheotomy was performed on average days after the intubation of the patients, after verification of the impossibility of the extubation of the latter either for central affection of the ventilatory controls, or reached the mixed nerves and disorders of the laryngo-pharyngeal intersection and according to expert recommendations in -tracheotomy should not be performed in the intensive care unit before the fourth day of mechanical ventilation. different pathologies that patients suffered and required tracheotomy were: post-operative complications of brain tumors (brain stem and mixed nerves) with patients, a rate of %, vascular pathologies (stroke and cvt)), with patients ( %), traumatic pathologies, with patients ( %). cases, %, cases of secondary bleeding of the orifice, cases of tracheal stenosis, and case of tracheomalacia. the decan made after pharyngolaryngeal neurological examination, and according to sfar recommendations experts suggest that a multidisciplinary decanulation protocol available in resuscitation departments. conclusion: tracheotomy in neuro-resuscitation has its place, especially in view of the different complications specific to this type of patient, but no study has demonstrated its improvement in vital prognosis. post-tracheotomy complications can be considerably reduced if the protocols and expert recommendations are applied. introduction: noninvasive ventilation (niv) in intensive care (icu) is associated with the occurrence of frequent asynchronies related to the leaks around the interface, mainly auto-triggering and delayed cycling. their detection requires a respiratory muscles activity monitoring. diaphragmatic ultrasonography is a simple imaging technique available at bedside to assess diaphragm motion. whether diaphragmatic ultrasonography would allow detecting asynchronies due to leaks during niv is unknown. the aim of this study was to assess two methods of diaphragmatic ultrasonography (excursion and thickening), coupled with the airway pressure signal to detect patient-ventilator asynchronies during niv. patients and methods: nine healthy subjects were placed under niv and subjected to intentional inspiratory and expiratory leakage on the ventilator circuit to generate delayed cycling and auto-triggering, respectively. the flow, airway pressure and diaphragmatic electromyogram were collected in order to identify the asynchronies generated by the leaks. in the meantime, an ultrasound recording of the excursion of the right diaphragm and of the thickening of the right diaphragmatic zone of apposition were performed and combined with the display of airway pressure on the ultrasound screen. these records were analyzed a posteriori to define the diagnostic performance [including sensitivity (se), specificity (spe), positive predictive value (ppv), and negative predictive value (npv)] of the excursion and the thickening to detect asynchronies. the experimental setup generated a median of asynchronies per subject (interquartile range - ). auto-triggering was correctly identified by continuous recording of both excursion (se = %, spe = %, ppv = %, and npv = %, fig. a ) and thickening (se = %, spe = %, ppv = %, npv = % + fig. c ). delayed cycling was detected with a slightly lower performance by diaphragm excursion (se = %, spe = %, ppv = %, npv = % + fig. b ) and thickening (se = %, spe = %, ppv = %, npv = % + fig d) . discussion: these encouraging results may be tempered by a variable effectiveness of the technique from one subject to another, in particular concerning the excursion. moreover, their generalization to critically ill patients may depend on several factors including echogenicity, stability and amplitude of the ultrasound signal in this population. conclusion: ultrasound is a simple clinical tool available at the bedside to detect delayed cycling and auto-triggering associated with niv leaks, provided that the airway pressure curve is displayed on the screen of the ultrasound machine. further studies are needed to assess its usefulness in detecting other types of asynchronies and its feasibility in critically-ill patients. introduction: although extra-corporeal co removal (ecco r) is not recommended, strong rational supports the concept. we aimed to describe our single-center experience of ecco r in the setting of mild to moderate acute respiratory distress syndrome (ards) and chronic obstructive pulmonary disease (copd). we performed a retrospective case note review of patients admitted to our tertiary regional intensive care unit (icu) and commenced on ecco r from november to august . demographic data, physiologic data (including ph and partial pressure of carbon dioxide in arterial blood [paco ]) before ecco r starting, and at day were recorded. results: twenty one patients received ecco r. thirteen were managed with hemolung ® device, seven with prismalung ® and one with ila ® . indication for ecco r were copd exacerbation (n = ), mild to moderate ards (n = ), uncontrolled hypercapnia due to pneumonia (n = ), and hypercapnia due to bronchial compression by mediastinal adenopathy (n = ). before starting ecco r, median minute ventilation, ph and paco were respectively . [ . , . conclusion: our observational cohort shows that ecco r therapy is effective to reduce paco and improve ph in the settings of mild ards and copd exacerbation. however, early weaning of sedation and pressure support ventilation might limit the decrease of respiratory rate and tidal volume. introduction: duchenne muscular dystrophy (dmd) is an x-linked recessive genetic disorder, caused by mutations in the dmd gene. respiratory failure is classical in the natural history of this disease. little is known about the diaphragm echographic pattern and the spectrum of patients with diaphragmatic paralysis in this disease. we aimed to assess the relationship between age and diaphragmatic motion and thickening fraction (tf) and to characterize the spectrum of patients with diaphragmatic paralysis. patients and methods: we included retrospectively dmd patients who experienced diaphragmatic echography and spirometry in our institution. diaphragmatic paralysis was defined as a diaphragm with tf < %. results: dmd patients were included in this study. all dmd patients were wheelchair bound. dmd patients had severe respiratory insufficiency with a median vc at % of predicted value [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . . % of patients were on home mechanical ventilation (hmv) and % were invasively ventilated. right diaphragmatic motion at deep inspiration was severely altered with a median of . mm [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . right tf of the diaphragm was severely altered with a median of . % [ . - . ] . . % of patients disclosed a paralyzed diaphragm pattern with a right tf < %. the age was inversely correlated with tf of the diaphragm (r = - . , p . ) and with the right diaphragm inspiration motion (r = − . p < . ). patients with diaphragm paralysis were older with median age at . years [ - . ], with severe respiratory impairment (median sitting cv = %) and median cumulated annual hmv duration at . years. conclusion: in dmd, age is inversely correlated with diaphragm function. diaphragm paralysis is frequent in older adult non-ambulant dmd. . the final probability model included the previous identified factors in addition to age and saps ii score, this model exhibited good calibration (hosmer-lemeshow x , p = . ) and good discrimination (roc-auc, . + % confidence interval, . - . ) (fig. ) . conclusion: our cohort study identified risk factors of icu death, mainly collected at admission among patients with aecopd. the proposed probability model has a good performance in predicting the short-term prognosis. further evaluation in other cohorts is needed. introduction: precarity is a complex notion including several components, and its definition is still debated. it is more subtle than financial poverty alone, and can increase population's health insecurity. we hypothesize that patients with precarity features may have different epidemiologic characteristics and icu outcomes than the general population. the aim of this study was to describe precarity features and outcomes of patients admitted to an icu located in a high poverty rate territory. patients and methods: we conducted a prospective single-center observational study of all patients admitted to icu of the saint-denis general hospital, from february to july . precarity features were classified in categories-absence of health insurance, lack of incomes or minimum allowances, homelessness or social home or hotel, and social isolation (no social link, or associations or neighbors). others social data were collected (speaking fluent french and education level) as well as usual clinical icu data. results: among patients included, precarity features were found in patients ( . %). income precarity was the most common, followed by accommodation precarity, health precarity and relation precarity (table ) . precarity was not associated with hospital mortality ( vs. . %, p = . ). all types of precarity were significantly associated with each other. precarious patients were younger ( vs. years-old, p < . ) and had less comorbidities. we found no differences concerning hospital or icu length of stay ( vs. days, p = . ) or concerning education level between precarious patients and the others. conclusion: our pilot study shows that precarity features are indeed very frequent and are often cumulated. with respect to the small patient sample, precarity does not seems to be associated with hospital mortality or length of stay. further investigations with larger patient samples and multicenter designs are warranted to investigate properly the impact of precarity on icu management and outcomes. introduction: population aging is a global and expanding phenomenon. elderly people are particularly vulnerable, and often need health care. this demographic evolution also affects intensive care units, and years old patient are now frequently admitted-it corresponds to % of admission in france. indeed we have analyzed the change in management of this very elderly people ( years old and more) over the past years in a french medical intensive care unit in a provincial university hospital. patients and methods: a retrospective cohort study was conducted using medical intensive care unit registry for demographic, physiological and diagnostic data from january to december . characteristics and treatment intensity during medical icu stay were specified, and short term and long term mortality were also recorded. results: a total of admissions, including octogenarians and older, were registered during the period. the proportion of very elderly people gradually increase from to %. intensity of treatment (organ support) increased from . from . per patient between the primary and the second part of the period, notably linked to mechanical ventilation ( vs. %, p < . ) and vasopressor infusion ( vs. %, p < . ). even if severity score increased (saps increase from . to . , p < . ), the icu mortality remains constant ( vs. . %). however, we were surprised to observe an increase in year mortality ( to %, p < . ). conclusion: between and , proportion of admission of very elderly people has increased two fold in our icu. although treatment intensity increases for more severe patients, icu mortality remains the same. nevertheless, absence of beneficial effect after year remains questioning. could icu to ward transfers and care course after hospital be optimized? lived alone at home, % in couple or with ther family, ( %) in retirement home and ( %) in nursing home. ( %) had a simplified ald score lower than indicating good functional independence. the more frequent diagnosis were acute pulmonary oedema and exacerbated copd. the mean simplified acute physiology score (saps ii) was ± . the treatment were were invasive mechanical ventilation ( %), only with noninvasive ventilation ( %), vasopressor agents ( %) and ( %) with renal replacement therapy. the average length of stay was . ± . days. after adjustment on sap-sii (without age), those invasive treatments were not associated with mortality no more than age. global mortality rate was %. ( %) were subject of a procedure for limiting therapeutics, among which ( %) died in the unit versus % for the other patients. the decision of therapeutic limitation was associated with severity of illness as measured by the sapsii (p = . ) but not with age. frequency of therapeutic limitation were similar in icu and intermediate care units. the mortality rate is lower than the older studies (s de rooij - %). unlike the study of p. biston ( ) which covers only the most serious cases, the mortality for any type of gravity remains reasonable. the procedure for limiting care were frequent especially for the most severe pathologies but all the patients who a decision of limiting care were stated were not dead. the patients over years old admit in french icu are very chosen. any major treatment appear to enhance mortality. introduction: due to advancements in medical technology and management of illnesses, an increasing proportion of critically ill patients are elderly. few information is available on the prognosis of these patients after icu discharge. the aim of this study was to analyze the clinical characteristics and long-term outcomes of elderly admitted to icu. patients and methods: monocentric, observational prospective study was performed. all elderly survivors (aged ≥ years) after an icu stay in a medical tunisian icu between january and december were included. data collected were: clinical features at admission, acute management procedures, functional characteristics and vital parameters (blood pressure, heart rate, abg's) at icu discharge. patients were followed during year via phone calls. a multivariate regression analysis was used to identify risk factors for one-year mortality. results: during the two-years study period, elderly patients were discharged alive. ( . %) were male. clinical features of elderly survivors were: mean age, . ± . years, median of charlson index, [ - ], chronic respiratory disease, ( . %), hypertension, ( . %) and diabetes ( . %). the most common reason for admission was acute respiratory failure in ( . %) patients and mean saps ii was . ± . . ( . %) patients required invasive ventilatory support, ( . %) vasoactive drugs and ( . %) received renal replacement therapy. the median of icu length of stay was days. the follow up was possible for ( . %) patients. mortality rate at year was . %. predictors of one-year fatal outcome in univariate analysis were as follows-saps ii (p = . ), heart rate at discharge (p = . ), decline in functional status (p = . ), world health organization (who) performance status at discharge (p = . ) and readmission within month (p = . ). multivariate regression showed that saps ii (or, . + % ci [ . - . ] + p = . ), who performance status at discharge (or, . + % ci [ . - . ] + p = . ) and heart rate (or, . + % ci [ . - . ] + p = . ) were independent risk factors of one-year mortality. conclusion: this study suggests that age and comorbidities should not be exclusion criteria for icu admission. in the long-term only saps ii, performance status and heart rate were significantly associated with one-year mortality in the elderly icu survivors. introduction: triage is an act performed at the entrance of emergency departments (ed's), it allows the classification of patients in different categories according to the seriousness and the priorities of treatment. vital emergencies are geared towards resuscitation room. in our ed, triage is not codified and is «done» in most cases by an unqualified staff. the aim of this work is to show the impact of absence of triage on the functionning of the resuscitation room. patients and methods: it's a prospective study, conducted in the ed of a university hospital, over months, including all patients over years old, admitted at the resuscitation room. epidemiological and clinical data of patients, their ccmu classification (classification clinique des malades aux urgences) have been specified, as well as their outcomes. we collected patients. the average age was . years old ( - years), for a sex ratio of . . forty patients ( . %) arrived «standing» at the ed. patients ccmu and represented . % of these admissions. the systolic blood pressure was under mmhg in % of cases, the glasgow coma scale < . in % of cases, and the spo < % in % of cases. mortality was . %. the other patients were admitted at the intensive care unit ( %), at the short stay hospitalization unit ( . %), at the operating room ( . %), or transferred to other departments ( . %). discussion: the patients ccmu and arrived by ambulance, «lying» , were considered as severe. the proximity of the resuscitation room of consultation rooms allows it to be used sometimes in flows' management and as a place of triage. the patients transferred straight to services didn't show signs of vital distress motiving their initial admission at resuscitation room or even at ed. those admitted at the short stay hospitalization unit were steady, but needed complementary examinations, specialized expert advice, or were waiting for a downstream bed. conclusion: a triage system must be introduced at the entrance of our emergency departments. the staff involved in that sorting must be identified, and disposing of a triage scale in order to figure out the degree of priority associated to patients conditions, and direct the ones needing urgent care towards the resuscitation room. results: one hundred patients were included, with average age of . years old ( - ) and sex ratio of . . these patients were brought to emergencies by their family in % of cases. reasons for admissions were varied, severe deterioration of their general condition ( %), alteration of consciousness ( %), respiratory distress ( %), convulsive seizures ( %). therapeutic interventions were cardio-pulmonary resuscitation ( %), fluid volume expansion ( %), mechanical ventilation ( %), administration of vasopressors ( %) and anticonvulsants ( %). mortality at the resuscitation room was %. thirty eight patients were admitted at the intensive care unit, equally at the short stay hospitalization unit (ssu) of ed. two patients returned home at the request of their family. discussion: these results show that ed's remain the last resort in front of oncology patient who is deteriorating, the occurrence of complications, and sometimes, the psychological exhaustion or family's obstinacy. emergencies departments continue admitting patients with terminal cancer, but are not organized for medium and long term care. the creation of a palliative care unit and the organization of home-based care will allow the prevention and treatment of complications as well as a psychological care, thus improving the living quality of these patients and their relatives. refusal of intensive care admission: assessment of a tunisian icu practices merhabene takoua introduction: need of intensive care exceeds its availability in several countries. as a consequence, rationing intensive care unit (icu) beds is common and often leads to admission refusal. purpose-to report refusal determinants and characteristics of patients associated with decisions to deny icu admission. this study was performed at the icu of abderrahman mami hospital, a -bed icu in ariana, tunisia. it was a prospective study enrolled between st january and th december . no predefined admission criteria were determined. decisions to admit are based on a combination of patient-related factors, severity of illness and bed availability. all consecutive patients referred for admission to icu during the study period were included. groups were defined gi-admitted patients and gii-refused patients. the reasons for refusal were categorized as follows: too well to benefit, too sick to benefit, patient or family refusal, necessity of other exploration not available in our institution and unit too busy. results: during the study period, icu admission was requested for patients of whom were admitted ( %). of the patients refused, only were admitted to icu later. refusal of icu admission came in % of cases from the emergency room and wards of our hospital, in % from other hospitals of whom % without icu. reasons of refusal were no beds availability ( . %), too sick to benefit from icu ( %), too well ( . %) and necessity of other exploration ( . %). no differences in demographic characteristic between the two groups were noted. among the refused patients, when compared with admitted patients, we found higher proportions of hematologic malignancies (p < . ) and cardiocirculatory arrest (p = . ). on the other hand, admitted patients were more likely to have cardio-respiratory comorbidities ( / vs. / , p = . ) and more need to mechanical ventilatory support ( vs. , p = . ). conclusion: our study confirms that icu refusal rate still high. it depends on both icu organization and patient characteristics. acute heart failure syndroms in intensive care: clinical features, management and outcome jamoussi amira , ajili achraf , merhebene takoua introduction: classification of acute heart failure (ahf) into clinical scenari (cs) was first proposed to facilitate early management ( ) . a decade after implementation of this approach, epidemiological and evolutive data based on this classification are interesting to investigate. that is why we aim to describe frequencies, management and mortality of each ahf syndrom in intensive care. a prospective study of patients > years with ahf admitted to the medical intensive care unit (icu) of abderrahmen mami hospital from january to august was conducted. patients were classified according to the clinical scenari ( ). clinical, therapeutic and outcome findings were recorded. results: during the study period ( months), we admitted patients in icu from whom ( . %) presented with ahf and then enrolled. the median age was of ± . years and sex-ratio . . a medical history of copd ( . %), hypertension ( . %), diabetes ( . %), ischemic cardiopathy ( %) and valvular cardiopathy ( . %) were noticed. at admission, severity assessement scores were: median apache ii . ± . and median saps ii ± . . clinical and evolutive characteristics according to clinical scenari are listed in table . conclusion: cs and cs are the most frequent ahf syndroms in icu and also have the best outcome. introduction: in cardiac arrest patients resuscitated from an ischemic ventricular fibrillation or tachycardia (vf/vt), both incidence and risk factors of recurrent severe arrhythmia are unclear. whether it is useful to give a prophylactic anti-arrhythmic (aa) treatment during the first hours and days is debated, particularly when a successful coronary reperfusion was provided. we aimed to evaluate the incidence of severe arrhythmia in patients resuscitated from an ischemic vf vt and to identify risk factors for developing arrhythmia during their icu stay. the procat registry captures all data from patients admitted in a tertiary hospital center after a resuscitated cardiac arrest (ca). we selected patients with an initial vf vt caused by an acute coronary syndrome (acs) and who were successfully treated with early percutaneous coronary intervention (pci) on admission. the primary endpoint was the recurrence of major arrhythmia between icu admission and icu discharge. all arrhythmias resulting in ca recurrence and or severe arterial hypotension requiring infusion of vasopressors were classified as major arrhythmias. multivariate logistic regression identified factors associated with the occurrence of major arrhythmias. results: between / and / , consecutive ca patients were included in the analysis. all patients underwent a successful pci of the infarct-related artery on hospital arrival. the only drug used as a prophylactic aa treatment was amiodarone, which was employed in / patients ( %). overall, / patients ( . %) had a major arrhythmia recurrence during their icu stay. a large majority of these major arrhythmia recurrences ( . %) occurred during the first h. characteristics of patients with and without major arrhythmia recurrence are described in the table . in multivariate analysis, public place location (or . [ . - . ], p = . ) and male gender (or . [ . - . ], p = . ) were both associated with a lower risk of major arrhythmia recurrence during the icu stay. prophylactic aa treatment was not associated with a lower risk of recurrences of major arrhythmias (or . [ . - . ], p = . ). conclusion: despite an early coronary reperfusion, more than % of our post-cardiac arrest patients experienced a recurrent severe arrhythmia during the post-resuscitation period, mostly during the first h in the icu. this proportion is much higher than what is reported in common acute coronary syndrome (without cardiac arrest) and further studies are needed to explore protective strategies. introduction: during symptomatic treatment of septic shock, markers of anaerobic metabolism may be used in a goal-oriented strategy. the recent international guidelines for management of sepsis and septic shock suggested guiding resuscitation to normalize lactate as a marker of tissue hypoperfusion. the purpose of this study was to evaluate the kinetics of lactate and other markers during the first three hours and to compare their levels between survivors and non survivors. we conducted a prospective, observational, single-center study of patients admitted to a general icu from the may to august . inclusion criteria were patients age ≥ , intubated and under mechanical ventilation with septic shock as defined by the third international consensus conference. simultaneous sampling of arterial and central venous blood gas were collected at h and h to obtain lactate (mmol/l), and scvo (%). delta pco (mmhg) and delta pco /cavo (mmhg/ml) were computed by our patient data management system and presented as a chart with additional hemodynamic data for clinical decision support. comparisons of values between groups were made by mann-whitney u test as appropriate. p < . was considered statistically significant. all reported p values are two-sided. statistical analysis was performed using systat ver. . . results: we studied intubated septic shock patients aged ± years, saps ii ± , sofa ± . . community pneumonia and peritonitis were the major sources of infection. icu mortality rate was %. all patients received norepinephrine ( . ± . µg/kg/ min), two patients received dobutamine ( . ± . µg/kg/min). the evolution of markers is summarized in table . at h and h , arterial lactate levels were higher in non-survivors than in survivors, but did not decrease at h in both groups. at h there was no statistical difference concerning scvo , delta pco and delta pco /cavo . after three hours of resuscitation, delta pco and delta pco /cavo ratio decreased and scvo increased in survivors. survivors had lower delta pco and delta pco /cavo ratio than non survivors. conclusion: although high lactate level is a key signal of anaerobic metabolism, it did not decrease during the first three hours in this group of severe septic shock patients. instead of using lactate, delta pco and delta pco /cavo kinetics could be integrated in a goaloriented strategy for septic shock resuscitation. introduction: to assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by oesophageal doppler (cidoppler). patients and methods: in patients, before infusing ml of saline, we measured cidoppler before and during the last seconds of successive -second end-inspiratory occlusion (eio) and endexpiratory occlusion (eeo), separated by min. patients in whom volume expansion increased cardiac index (transpulmonary thermodilution) > % were defined as "fluid responders". results: eeo increased cidoppler more in responders than in nonresponders ( ± vs. ± %, respectively, p < . ) and eio decreased cidoppler more in responders than in non-responders (- ± vs. - ± %, respectively, p = . ). thus, when adding the absolute values of changes in ci observed during both occlusions, cidoppler changed by ± % in responders and ± % in nonresponders. fluid responsiveness was predicted by the eeo-induced change in cidoppler with an area under the receiver operating characteristic (roc) curve of . ( % confidence interval- . - . ) and a threshold value of % increase in cidoppler. it was predicted by the sum of absolute values of changes in cidoppler during both occlusions with a similar area under the roc curve ( . ( . - . )) and with a threshold of % change in cidoppler, which is more compatible with oesophageal doppler precision. in this case, the sensitivity was ( - )% and the specificity was ( - )%. conclusion: if consecutive eio and eeo change cidoppler > % in total, it is very likely that volume expansion will be efficient in terms of cardiac output. the measurement of cardiac output using a signal morphology-based form of impedance cardiography (physioflow ® ) in intensive care unit: comparison with the trans thoracic echocardiography. introduction: in the intensive care units, the cardiac output (co) is one of the main hemodynamic parameters required to manage patients in shock. the physioflow ® is a new non-invasive method using the waveform analysis of the thoracic impedance signal (ti) to assess co. in hemodynamicaly unstable patients, no studies have evaluated the level of agreement between the co estimated by transthoracic echocardiography (co-tte) and that measured using the waveform analysis of thoracic impedance physioflow ® (co-ti). the objective of this study was to evaluate the ability of co-ti relative to co-tte to estimate the absolute co value and detect the expected variation co (v-co) in critically ill patients. patients and methods: fourteen patients sedated and mechanically ventilated, in shock under catecholamines and monitorred with tte and ti physioflow ® were included. hemodynamic datas, stroke volume (sv) and co with two monitoring were performed at baseline min before passive leg raising (plr), s after plr and min after volume expansion (ve) of ml of saline solution. responders were defined by an increase > % of cardiac output (v-co) after plr. results: fourteen pairs of tte and ti measurements were compared. the median (iqr) age was years ( - ), igs was ( - ). only patients were responders after plr. there was a significant correlation between the co-tte and co-ti measurements (r = . , p < . ). the median bias was . l/min and the limits of agreement (loas) were − . and . l/min. there was a significant correlation between v-co-tte and v-co-ti (r = . , p = . ) (fig. ) . the median bias was- . % and the loas for v-co were respectively - . and + . %. conclusion: the co measured with physioflow ® , a signal morphology-based impedance cardiography, is correlated to the co measured with tte. however, the high loa observed in this preliminary study underline the necessity to remain careful and wait for further inclusions. - ] vs. . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days, p = . ). despite imbalancedunderlying characteristics in terms of demographics and comorbidities, in-icu mortality rates were similar between patients ( . vs. %, p = . ). conclusion: prior bb treatment have limited impact on the severity of acute circulatory failure in septic shock and is not associated with increased mortality despite the underlying frailty of patients. introduction: cardiac output monitoring is a key component in the management of critically ill patients. cardiac output estimated by transthoracic echocardiography is documented in patient with atrial fibrillation, but a large part of transpulmonary thermodilution validation studies excluded this specific population. the objective of this study was to evaluate cardiac output mesurement and trend ability by transpulmonary thermodilution relative to transthoracic echocardiography in critically ill mechanically ventilated patients with atrial fibrillation. patients and methods: thirty mechanically ventilated patients requiring hemodynamic assessment were included in a prospective observational study. cardiac output was mesured simultaneously with transpulmonary thermodilution and transthoracic echocardiography. seventy-four pairs of cardiac output measurements were compared. the two measurements were significantly correlated (r = . et p < . ). the mean bias was - . l/min, the limits of agreement were - . and + . l/min, and the percentage error was . %. thirty-four pairs of cardiac output variation measurements were compared. there was no significant correlation between cardiac output variation measurements by transpulmonary thermodilution and transthoracic echocardiography. the mean bias was − . l/ min and the limits of agreement were − . and + . l/min. with a % exclusion zone, the four-quadrant plot had a concordance rate of . %. the polar plot had a mean polar angle of . ° with % confidence interval between − . ° and . °. conclusion: in critically ill mechanically ventilated patients with atrial fibrillation, cardiac output measurements with transpulmonary thermodilution and transthoracic echocardiography are not interchangeable. introduction: basic critical care echocardiography (cce) relies on transthoracic echocardiography (tte). we sought to assess the diagnostic capacity of a next-generation micro-digital broadband beamformer in patients with cardiopulmonary compromise. all patients with acute circulatory respiratory failure underwent two basic tte assessments using successively a next-generation micro-digital broadband beamformer ( elements, - mhz) incorporated in a sector phased array probe with twodimensional, m-mode and color doppler mapping capacities which was connected to a touchscreen interface (lumify, philips), and using a compact full-feature imaging system ( elements, - mhz + cx , philips). tte examinations were independently performed in random order by two intensivists with expertise in cce, within a -min time frame without therapeutic intervention. imaging quality was graded from (no image in the corresponding view) to (clear identification of % of endocardial boarders). the concordance of qualitative data was assessed using the kappa test and agreement of two-dimensional measurements (left ventricular end-diastolic diameter [lvedd], ratio of right ventricular (rv) and lv end-diastolic diameters [rvedd lvedd] + end-expiratory inferior vena cava diameter [dexpivc]) was evaluated using intraclass coefficient correlation (icc). results: thirty consecutive patients were studied, without any exclusion for absence of tte images (age, ± years, sap-sii, ± , % ventilated, % under catecholamines, lactate, . ± . mmol l). the proportion of echocardiographic views eligible for interpretation and mean duration of tte examinations were similar with the miniaturized and full-feature systems ( vs. %, . ± . vs. . ± . min, p = . ). two-dimensional imaging quality grade was lower with the miniaturized system ( system. concordance of two-dimensional measurements was also good-to-excellent (table ) . conclusion: for basic cce use, next-generation micro-digital broadband beamformer appears providing reliable information with good-to-excellent diagnostic capability, accurate two-dimensional measurements, and adapted therapeutic suggestions. these preliminary data require further confirmation. introduction: acute kidney injury (aki) in very old patients (over years) admitted in intensive care unit (icu) is a frequent issue and is known to be associated with a severe prognosis. we aimed at describing the clinical characteristics and prognosis of such a population. the objective of the study was dual: first to evaluate the short and long term mortality of these patients, second to determine the factors associated with a poor outcome. patients and methods: we conducted a descriptive, retrospective and monocentric study based on the hospital records of patients over years with aki admitted in our icu between january and december . the patients were selected according to the kdigo criteria ( ) . survivals at the discharge from hospital, at day and at year were assessed. the factors associated with mortality at year were scrutinized. results: after excluding patients for an initial therapeutic limitation, the data of remaining patients were reviewed. the patients were years old (interquartile range, iqr - ) and were predominantly male gender ( %). saps ii and sofa score at admission were (iqr - ) and (iqr - ) respectively. % of the patients needed for mechanical ventilation and % of them needed for catecholamine use. septic ( %), prerenal ( %), iatrogenic ( %) and cardiogenic injury ( %) were the leading cause of aki. dialysis was performed in % of patients. the overall mortality at the discharge from icu, at day and at year was , and % respectively (fig. ) . neither were the age, the comorbidities, the etiology of aki nor the need for dialysis associated to a significant increase in mortality. a stepwise cox regression analysis revealed saps ii and blood lactate level at icu admission as independent risk factors associated with year mortality. conclusion: aki at admission in icu is associated with a high mortality at year in an elderly population. main long term prognostic factors are linked to the initial severity at icu admission. introduction: the proportion of elderly around the world doesn't stop growing and increases the consumption in health care. however, lots of studies report the impact of the age on the decision to admit a patient to the icu despite no triage recommendation exists. the primary objective was to determine prognostic factors of death for the years and over at admission to the icu and secondly to evaluate their functional prognostic at short and medium term after their exit. patients and methods: prospective and observational study conducted in our icu beds unit from august to february . patients of years and over were listed. the dying patients arriving after a pre-hospital resuscitation for whom no therapeutic plan has been initiated and those admitted for an organ donation were excluded. the primary outcome was the duration between the admission and the potential death during the follow-up. the secondary outcomes were the necessity to entry an healthcare institution or the loss of one autonomy point on the adl french scale after the hospitalization. results: patients of the admissions were included. the igs ii and sofa average scores were respectively . ± . and . ± . . the most common diagnosis were a septic shock ( patients), a cardiopulmonary arrest ( patients), a cardiogenic shock ( patients) and a pulmonary oedema or a lung infection ( patients fig. survival of very old patients with aki in icu (%) each). patients ( . %) died during the follow up- at the icu, during ward and during re-education or after their home return. from a multivariate analysis (table ) , anisocoria, cardiopulmonary arrest and acute kidney injury (aki > ) seem to be independent risk factors of death. patients were alive at the end of the follow up. recovered their previous autonomy, needed a place in a specialized institution. all the other lost a part of autonomy months after their home return with the average loss of one point on the adl autonomy french scale. conclusion: anisocoria, aki and cardiopulmonary arrest seem to be independent risk factors of death for those patients. concerning the survivors, a stay at the icu lead to an increased dependency. other studies have to be led to evaluate which of our patients could have get the best benefit of their stay to prevent from a misuse of the structure. introduction: context-among the severe complications of preeclampsia, acute kidney injury (aki) poses a dilemma if features of thrombotic microangiopathy (tma) are present. although a hellp syndrome is considerably more frequent, ruling out a flare of atypical haemolytic and uremic syndrome (hus) is then of utmost importance. objective-to improve the differential diagnosis procedure in cases of post-partum aki. patients and methods: a hundred and five cases of post-partum aki, admitted in the last years ( ) ( ) ( ) ( ) ( ) in french icu from different regions, were analysed. initial and final diagnosis, renal features, haemostasis and tma parameters were all analysed, paying a special attention to their dynamics within the first days following the delivery. results: the main circumstances of aki were severe preeclampsia (n = ), post-partum haemorrhage (pph, n = ) and primitive tma (n = , including atypical hus and thrombotic thrombocytopenic purpura). among the thirteen cases of renal cortical necrosis, were associated with preeclampsia. congruence between the initial and the final diagnosis was low ( %). thus, none of the women referred to our centers for a suspicion of non-placental tma has received a final diagnosis of non-placental tma (and instead had a pe or a pph). conversely, all women with a final diagnosis of nonplacental tma were referred for a suspicion of pe-related tma, or with a pph which polluted the diagnosis. tranexamic acid was largely used in the context of pph ( %), at a dose up to grams total. taking into account the final diagnosis, we subjectively concluded that plasma exchanges and eculizumab were abusively indicated in and cases, respectively, of typical hellp syndrome. plasma exchanges were in itiated in all cases, a mean h following the admission. dynamics of hemoglobin, haptoglobin, and liver enzymes were poorly discriminant. the dynamic pattern of ldh and of platelets, in contrast, was statistically different between primitive tma-related aki and other groups-at day , platelets increased in preeclamptic women, and in other circumstances, but not in patients with primitive tma. a classification and regression tree (cart) independently confirmed the usefulness of platelets and ldh trajectory in the diagnostic algorithm (fig. ) . conclusion: the trajectory of ldh and platelet count is useful to identify the cause of post-partum aki, and the clinician may reasonably take therapeutic decisions at day post-delivery. introduction: continuous veno-venous hemofiltration (cvvhf) is a common practice in intensive care units (icu). because it is continuous, the choice of anticoagulation is essential-regional anticoagulation fig. analysis of post-partum aki cases with citrate or systemic with unfractionned heparin or low molecular weight heparin (lmwh). filter's lifespan is a major issue regarding filtration's effectiveness and cost. in this study, we compared the filter's lifespan between lmwh and citrate anticoagulation. patients and methods: a monocentric retrospective study was led from january to october . all the cvvhf sessions during this period were included. prismaflex© monitors (hospal) were used. practioners were free to choose between citrate or lmwh defining groups. we aimed a post filter ionized calcemia between . to . mmol/l in citrate group + and a post filter anti xa activity between . to . ui/ml in lmwh. results: cvvhf sessions were included- with lmwh anticoagulation, and with citrate. patients were years old on average, primarly males ( %), with an initial average saps ii score of . icu mortality was %. patients' hemostasis was measured before each cvvhf session, without any significant difference between the groups. global filter's lifespan was h + h in citrate group versus h in lmwh, without significant difference (p = . ) (fig. ) . no serious side effect, especially hemorrhage in the lmwh group, was reported. filtration efficiency, represented by the urea reduction ratio during the first cvvhf session, was similar, % ± % in lmwh group versus % ± % in citrate group (p = . ). conclusion: both anticoagulation-systemic with lmwh or regional with citrate can be used in icu. both methods enable long and comparable filter lifespan, with similar filtration efficiency and without serious adverse events. our results need to be confirmed by a randomized propective study. introduction: arf during the post-partum period is a rare complication. the main etiologies are post-partum haemorrhage (pph) and thrombotic microangiopathy (tma). rrt may be required. the aim of this study was to identify variables associated with rrt in this population admitted in icu. patients and methods: we conducted a study using retrospectively collected data in a cohort of patient with post-partum arf according to the kdigo criteria and requiring icu in the university hospital of lille from until . two groups were compared-rrt and non rrt patients. demographic and obstetrical data as well as data during icu stay and patients' outcome were collected. etiologies of arf, kdigo stage, anuria, hemolysis parameters and biological data at icu admission were studied. comparisons were made using a chi-two or fisher exact test or a mann-whitney u test. odds ratio (or) for the statistically different criteria were studied. results: twenty-two patients requiring rrt were compared to the patients without rrt. the two main etiologies of arf were tma ( . %) and pph ( . %). vaginal delivery was significantly more frequent in the rrt group compared with caesarian delivery (p = . ). use of rtt was significantly increased after pph compared the others etiology of arf (p = . ). in the rrt group, the icu length of stay was longer (p < . ) and igs ii score was higher (p < . ). higher kdigo score was observed in rrt patients (in the rrt group-kdigo = , = %, = %, and without rrt-kdigo = . %, = %, = %, p < . ). anuria h after icu admission was more frequent in cases of rtt ( . % versus . %, p < . ). hemolysis was greater in rrt patients with lower haptoglobin (p = . ) and increased lactate deshydrogenase (ldh) (p = . ). the association with rrt requirement was stronger with the duration of anuria, with an or at h at . [ . - . ] and at h at . [ . - ] . a lower haptoglobin was associated with a higher risk of rtt (or . [ . - . ]), as well as pph (or . [ . - . ] ) and vaginal delivery (or . [ . - . ]). conclusion: hemolysis parameters and anuria seemed useful criteria to identify patients at higher risk of rrt early during their icu admission. introduction: renal replacement therapy (rrt) has three aimsrestoring homeostasis, ensuring survival and preserving the potential for renal recovery. the main indication of rrt in icu is acute renal failure, correlated with a very important rate of mortality despite the progress made in its management. patients and methods: the objective of this work is to take stock of the indications and the objectives of the rrt in icu. through a prospective study, we report a serie of cases, collected at the multipurpose resuscitation unit of the avicenna military hospital in marrakech between september and september . results: the average age of our patients is , ± , years with extremes ranging from to years and a male predominance ( %). the main reasons for admission were hemodynamic distress in . % of cases, followed by septic shock in . % of cases, neurological and respiratory distress were noted in . and . % of cases, respectively. rrt indications were severe acidosis in % of patients, followed by % hyperkalaemia, acute pulmonary edema in %, hemodynamic instability in patients with chronic renal failure in %, acute renal failure in %, and hyperuriaemia in % of cases. the technique chosen is conventional intermittent hemodialysis with a synthetic membrane. the main duration of the sessions was h min ± mn. vascular access was a right internal jugular catheter in . % of patients and left in . %, right femoral catheter in . % of patients and left in . %, arteriovenous fistula (fav) and a tunneled catheter in . and . % of patients. mortality was , %, chronicity progressed in . % of cases and total or partial recovery of normal renal function in % of cases. conclusion: we have a high rate of mortality in our icu that's why we will focus on prevention of risk of renal failure in our patients. introduction: there is limited information on the outcome of acute kidney injury (aki) in patients with traumatic intracranial hemorrhage (tich). tich patient with aki was related high mortality rate. the aim of this study is to estimate the outcome using different renal replacement therapy on the survival rate and rate of long term renal-replacement therapy in adult tich patient. patients and methods: we retrospectively identified a total of tich patients with aki who required glycerol or mannitol therapy admitted to the intensive care unit during a -year period ending dec from the national health insurance research database. demographic data, severity of tich, medication, level of care, type of head surgery were collected. all patients subjects were older than > years. we also excluded patients diagnosed with tich before the cohort entry date, hemodialysis before tich, chronic kidney disease cancer coagulation defects purpura and other hemorrhagic conditions, mortality mechanical ventilation ischemic heart disease before tracking. the primary outcome was overall survival at day . the secondary outcome was the rate of long term hd therapy. results: a total of patients were enrolled. the kaplan-meier estimates of mortality at day did not differ significantly between the continuous veno-venous hemofiltration (cvvh) and hemodialysis (hd) strategies + deaths occurred among patients receiving cvvh-strategy group and deaths occurred among patients receiving hd-strategy group (adjusted hazard ratio: . , % ci . to . ; p = . ). the rate of long term hd was higher in the hd-strategy group than in the cvvh-strategy group ( . vs. . %, p = . ) especially in injury severity score ≥ group (table ) . discussion: in our study, tich patient with aki receving cvvh may have effect on renal blood flow protection or cytokine removal which lower the rate of long term hd. conclusion: these clinical data provides readers interventions to improve outcomes in this population and future study are needed to confirm the result. this study highlights the importance different renal replecement therapy in the tich with aki population (table ) . khaleq khalid , hattabi khalid , bensardi fatima zahra , bouhouri m. a , nciri a , hamoudi d , alharrar r introduction: the combined progress of abdominal surgery and anesthesia lead to more frequent surgical indications, including for fragile patients or serious pathologiespostoperative morbidity and mortality is an element that requires evaluation and analysis in surgical resuscitation. although pathological processes and new therapeutic approaches in surgery are currently well known, data on risk factors for morbidity and mortality are less available. the aim of our work is to evaluate the post-operative morbidity and mortality rate and to identify the main predictive factors. patients and methods: a retrospective-cohort, unicentric study that included all consecutive patients hospitalized in the surgical resuscitation department after abdominal surgery regardless of the operated organ, during years. the structured sheet of data collection included more than items on all perioperative data concerning the patient, the disease, and the operating surgeons. postoperative mortality and morbidity were defined as in-hospital death and complications. a first descriptive analysis of the various parameters collected was carried out a bivariate analysis was then performed to study the factors affecting morbidity and mortality in digestive surgery the comparison was made using the student's t test for quantitative variables and the chi square for the qualitative variables. a difference is considered significant when p < . ( %). results: among patients, the in-hospital death rate was . % and the overall morbidity rate was . %, the mean age was . ± , years with extreme ages of years and years with sex ratio of . . five factors were incriminated in post: operative mortality notably:renal failure p = . , duration of stay p = . , parenteral nutrition p = . , long duration of intubation p = . , perioperative blood transfusion p = . . three factors influencing morbidity were found: duration of stay p = . , parenteral nutrition p = . , long duration of intubation p = . . conclusion: knowledge of the true frequency of both mortality and morbidity is crucial in planning health care and research and identifying risk factors. introduction: tools to quantify and assess bowl management in critically ill are still very limited and often over-looked. with the primary fig. filter's lifespan concern of optimizing patients to preserve life, the problem of bowel care has been given less priority. the aim of this study was to use ultrasonographic measurements of gastric emptying in the critically ill as a tool of measurement of the impact of different specific factors of icu stay on bowl emptying. patients and methods: this is a prospective study conducted in an intensive care unit for months. it included patients. ultrasonic imaging of antral sections was undertaken every min for the first h and every min thereafter until total emptying. correlation analyses were calculated, applying an adjusted significance level (pb < . ) to correct for multiple testing. results: all our patients were above the age of . the median of age was years old . of our patients were male and were female. the total emptying median time was ± min. significant correlation was observed between length of stay and delay in bowl emptying. mechanical ventilation had also significant relation with slower bowl progression and gastric emptying. patients in septic shock had tendencies to earlier delayed bowl emptying compare to others patients included in our study. conclusion: the study we conducted is a pilot study. further studies should be conducted and unltrasonografic gastric assessment could be standardized in protocols to assess clinical decision making and improve nutrition and bowl management in icu patients. introduction: enteral nutrition, via a feeding tube, is often used in intensive care units (icu) to supply artificial nutrition to critically ill patients. the feeding tube is also commonly used to administrate drug therapy as well. however, there is a lack of knowledge of the nurses about this way of administration. this could be a potential source of medicine-related illness. the purpose of this study was first, to evaluate the nurse's knowledge on enteral drug administration, and second, to observe nurses and to evaluate the adequacy of their practices with guidelines, and to report medication-administration errors. patients and methods: this prospective study using the observation technique was conducted in icu (one medical and one surgical). first, a knowledge and practice questionnaire regarding drug administration trough enteral feeding tube was filled by each intensivist nurse. secondly, pharmacist performed observations of nurses during preparation and administration of medications. these practices were compared with the original medical prescription and with the data available in the literature. results: questionnaires were returned. nurses evaluated their knowledge as medium and as inadequate. there was a lack of knowledge on the type of drugs which can be used by feeding tube ( wrong responses). nurses and different drugs were observed during the drug administration phase. no administration totally complied with our institutional protocol, particularly the crush of tablets. when a tablet was crushed, in % an alternative formulation (in syrup for example) existed. the correct administration of drugs in feeding tubes is important and represents a challenge in icu. firstly, crushed tablets is the most frequent cause of obstruction of feeding tubes which have to be changed + secondly, crushed tablets destroys the controlled release of enteric coated dosage forms, resulting in a higher or a lower initial blood level. we have to train nurses for drug administration by feeding tube. on their daily ward, the pharmacist should improve the choice of medication's forms. introduction: acute variceal hemorrhage (avh) is a severe complication of portal hypertension. in addition, the variceal bleeding is still the most common lethal complication of cirrhosis. the most effective modality of treating is based on resuscitation combined with the endoscopic variceal band ligation. the purpose of this preliminary study was to find the factors associated with poor prognosis of avh in cirrhotic patients. patients and methods: this is a retrospective study, spread over months between january and december . are included all consecutive patients with liver cirrhosis hospitalized for variceal bleeding. we exploited the medical records to identify the clinical, biological and endoscopic parameters. results: a total of patients hospitalized for avh occurred during the study period. the mean age at admission was years, and are female. cirrhosis was post viral in % of cases. patients were classified as child-pugh c in % of cases. the median presenting model for end stage liver disease (meld) and clif sofa were respectively and . . twelve ( ) patients received beta-blockers and have required at least one endoscopic variceal band ligation at the time of the bleeding episode. in the acute phase, pharmacological treatment based on vasopressor (sandostatin)) was instituted in all cases and combining with antibiotic prophylaxis (c g or fluoroquinolone) in cases. in cases the endoscopy was made within h, active bleeding at endoscopy was observed in patients. esophageal avarices (ov) were grade i ( patients) grade ii ( patients) and grade iii ( patients). the eradication of varices was obtained in patients ( . % percentage of the cases). the variceal bleeding recurred in of patients ( %of cases) and patients died which within the first days. spontaneous bacterial peritonitis (p . ), hepatic encephalopathy (p . ) and the hemodynamic instability with schok (p . ) are correlated with early mortality at days. hepatic encephalopathy (p . ) and bacteremia (p . ) are corrolated with week motality. non selective betablocker (p . ) and primary use of band ligation when indicated (p . ) are protective factors and parameters of good outcome. conclusion: despite developing of endoscopic tools and respect of actual therapeutic guidelines in avh, the outcome is still poor. the prognosis appears to be dependent on the clinical condition at admission and primary prevention. introduction: the french intestinal stroke center based on a multimodal and multidisciplinary management has been developed to improve survival and intestinal viability. open surgical revascularization was decided for patients unsuitable for radiological revascularization and or suspected of intestinal necrosis. we aimed to study the prognosis of patients suffering from aoami in icu and who have benefited from open revascularization. single-center, observational and prospective study was carried out in a surgical icu of a tertiary center. patients with aoami managed in our intestinal stroke center from to and who underwent open revascularization were included. results: data of patients were collected. patients' characteristics are described in table . all patients had abdominal computed tomography angiography at the diagnosis, and patients ( %) presented signs of intestinal injury. thrombosis was the main mechanism of superior mesenteric artery (sma) occlusion ( patients, %). all patients received antiplatelet therapy, curative unfractionated heparin therapy and digestive decontamination. open revascularization was performed by sma endarterectomy ( patients, %), sma surgical bypass ( patients, %), retrograde open mesenteric stenting ( patients, %) and coeliac artery bypass ( patients, %). three patients ( %) underwent a radiologic endovascular revascularization attempt before open repair. small bowel resection ( cm ) was achieved in patients ( %). four patients ( %) had peritonitis. six patients ( %) had one or more relaparotomy ]), usually for hemodynamic instability ( %). only one patient died in icu ( %). icu lenght of stay was days ] and duration of mechanical ventilation was days [iqr - ]. overall, haemodynamic failure was present in patients ( %). median duration of vasoactive support was days [iqr - ]). severe acute respiratory distress syndrome was observed in patients ( %) and acute kidney injury in patients ( %, including patients who received renal-replacement therapy, %). enteral feeding was initiated in patients ( %) with a delay of . days [ . parenteral nutrition was administered in patients ( %), including patients ( %) without enteral feeding. five patients ( %) were discharged with small bowel syndrome. conclusion: icu patients who underwent open revascularization to treat aoami as part of a multimodal and multidisciplinary management in a dedicated intestinal stroke center have low mortality and intestinal resection rates. larger studies are needed to confirm these results. introduction: precise consequences of late transit in icu remain elusive. we have previously shown that defining late transit by the absence of stool within days after admission was not relevant because it did not identify a group of patients with specific outcome [ ] . to further improve this definition, we investigated the differences in outcome among patients according to their bowel movements frequency. patients and methods: preliminary results of a prospective, two centers, observational study. all patients admitted to icu, with a length of stay (los) of at least h were eligible and included with the following exceptions-abdominal surgery, bowel infection or any baseline condition known to alter transit time. patients were compared according to stool frequency-less than %, between and %, between and % or more than % of icu days. we also tested the former constipation definition of more than days after admission without stool passage. we registered demographic data, time spent under mechanical ventilation (mv), icu los, ventilation associated pneumoniae (vap) and vital status at discharge. results: over months, patients were screened and ( . %) were included, age . ± . years, mean saps ii ± , ( . %) mechanically ventilated. the most frequent exclusion criteria were los < h (n = ). % of the patients had stool less than % of icu days. patients with fewer bowel movements were more likely to be mechanically ventilated, without association with time spent under mv. there was a link between the time to first stool after admission and the stool frequency during icu (p < . vap n(%) ( . ) ( . ) ( . ) ( . ) death n(%) ( . ) ( . ) ( . ) ( . ) discussion: this study is limited by the number of patients leading to an imbalance between subgroups therefore limiting the comparison. conclusion: these preliminary results do not plead for an improvement of the late transit definition based on the frequency of stool. further data is warranted to better define this condition, and the management to provide. introduction: antibiotic therapy during acute exacerbation of copd (aecopd) still controversial and not well supported by clinical evidence. in fact half of these episodes are caused by viruses even during severe episodes with need to ventilator support. procalcitonin is effective to guide antibiotic therapy during acute exacerbation of copd without compromising patients' outcome, its efficacy in the intensive care setting still not well evaluated. we have conducted in a bed icu a before after study. during the first period (january -december ) patients with aecopd were included retrospectively and treated with antibiotics according to anthonisen criteria (control group). in the second period (january -may ) antibiotics were prescribed only if the procalcitonin level was greater than . ng ml (procalcitonin group). results: ninety-two patients were included, in the procalcitonin group and in the control group. antibiotics were administered at icu admission in patients ( %) in the procalcitonin group and in ( %) patients in the control group, p = . . only % of sputum cultures were positive at icu admission. time to recovery was similar between the two groups [ iqr ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , iqr ( - ), p = . ]. other patients' outcomes did not differ between the control group and the procalcitonin group with respectively: the mortality ( . vs. %, p = . ), the incidence of pavm ( vs. %, p = . ) and niv failure ( vs. %, p = . ). readmission to the hospital at day was significantly higher in the control group ( vs. %, p = . ). conclusion: using procalcitonin to guide antibiotic therapy during severe aecopd can reduce the use of antibiotics without compromising patients' outcomes. our study aimed to assess whether arc impacts negatively on cefazolin pharmacokinetic pharmacodynamics (pk/pd) target attainment and clinical outcome in critically ill patients. patients and methods: over an -month period, all critically ill patients treated by cefazolin for a documented respiratory infection without renal impairment were eligible. patients who underwent an empiric antimicrobial treatment > h before introduction of cefazolin were not included. during the first three days of antimicrobial therapy, every patient underwent -hour creatinine clearance (crcl) measurements and therapeutic drug monitoring at steady state. the main outcome investigated in this study was the rate of pk pd target non-attainment defined by an unbound concentration < µg ml (mic value for inoculum > ufc ml). the secondary outcome was the rate of therapeutic failure, defined as an impaired clinical response with a need for escalating antibiotics during treatment and or within days after end-of-treatment. results: over the study period, patients were included ( samples analyzed for therapeutic drug monitoring). in pharmacological analysis, the rate of pk pd target non-attainment was %, with a strong association with crcl (p = . ) ( table ). in clinical analysis, the rate of therapeutic failure was % ( ), with a strong association with inoculum effect (p = . ). there was a strong association between therapeutic failure, crcl > ml min and pk pd target non-attainment adjusted on the inoculum effect (p = . ). introduction: vancomycin has long been used as the standard therapy of infections due to methicillin-resistant staphylococcus aureus (mrsa). the side effects of this drug as well as the increasing resistance and its pharmacodynamics effects have fostered the development of newly active drugs. nevertheless it is still widely prescribed and it stands as the mostly used comparator in randomized study. an assessment of our medical practice regarding its use may enhance compliance to guidelines so as to promote a better use of vancomycin. patients and methods: in our bed hospital, the incidence rate of mrsa fell from . to . per patient days from to whereas the current proportion of mrsa isolates is about %. vancomycin is the most prescribed empirical or targeted antibiotic therapy covering mrsa in our medical intensive care unit of beds even if a shift towards the use of linezolid in nosocomial pneumoniae has been noticed during the last years. key points regarding the proper use of vancomycin have been implemented in our antibiotic stewardship program. moreover courses concerning this topic are provided to our junior doctors. a retrospective review of the quality of antibiotic use has been carried out in courses of vancomycin therapy and the following criteria have been assessed-indication, dosing schedules, serum levels of vancomycin, duration of antibiotic therapy and the overall degree of conformity of the prescription. results: regarding indication, conformity was observed in cases ( %). the dosing schedule was appropriate in cases ( %) only. of the remaining cases ( %), all of them were not adjusted to the serum concentration and in cases ( %) the general dosing recommendation was not respected. the loading dose was inappropriate in cases ( %) and the proper follow up of serum levels of vancomycin has not been carried out in cases ( %). the duration of antibiotic therapy was in compliance with the protocol in cases ( %) and a slight longer duration was observed in cases ( %). finally the overall degree of conformity of the prescription was observed in cases ( %) only. table . in the sfar srlf guideline, the limitation of the echinocandins use to the benefit of ampho deoxycholate explains most of the poor agreement or consensus rate between investigators. the idsa escmid guideline are more helpful to guide indications of empirical treatment which mainly explains their higher rate of both applicability and agreement rate. the rates of agreement do not reflect whether the choice between different class iii antifungal therapies is the best or not. conclusion: the idsa guideline seems to take a broader spectrum of clinical situations into account, particularly in guiding more precisely indications of empirical treatments. escmid or idsa reach more often consensus at the first reading. ( ), and was discovered during a chest x-ray examination for % ( ). diaphragmatic paralysis was confirmed for all cases with chest ultrasound. % of patients ( ) were receiving mechanical ventilation at the moment of the diagnosis. the paralysed hemidiaphragm was left sided in % ( ), and right sided in % ( ). there was no bilateral diaphragmatic paralysis. hemi-diaphragmatic plication was performed in % of the patients ( ), and median time from cardiac surgery to surgical plication was days (range - days). indications for plication were failure to wean from ventilator ( %, ), and respiratory distress ( %, ). plicatured patients were remarkably younger (median age at cardiac surgery- days, range - days) than non-plicatured patients ( . months, range days- years). the median ventilation time after plication was days (range - days). all patients were asymptomatic after diaphragmatic plication. two patients died ( %). cause of death was independant from surgical plication (cardiogenic shock, septic shock). conclusion: diaphragmatic paralysis is a rare but serious complication of cardiac surgery in children. it commonly occurs after open-heart surgery, and specifically after arterial switch operation. plicatured patients were younger than non-plicatured patients and needed more frequently a ventilatory support. a closer monitoring may be required for young patients and mechanically ventilated patients. indeed, both are more likely to be treated by a diaphragmatic plication, reducing mechanical ventilation and intensive care duration. a prospective study. consecutive children aged between days and -year-old admitted to the picu, intubated and mechanically ventilated were eligible and they reached inclusion if they had at least one chest tube. ppl was directly measured by a pressure transducer connected through a needle inserted into the existing chest tube. pes was measured by both a specific probe (gaeltec probe) and by the feeding tube after mobilization (pes-ft). results: patients (median age months (interquartile + - )) were included and exploitable signals were finally available in patients, who were included in the analysis. most of patients (n = ) were admitted after cardiac surgery and had a spontaneous breathing activity. median pes measured by gaeltec probe and by feeding tube was . (interquartile + . - . ) and . ( . - . ) cm h o, respectively. median ppl measured into the chest tube was . ( . - . ) cm h o. bland-altman plots are represented in the figure. conclusion: both ppl measured into the chest tube, pes measured by the gaeltec probe or by the feeding tube are reproducible methods. . respiratory syncytial virus was identified in infants ( %). an initial caffeine citrate loading dose of mg kg was usually administered, followed by a mg kg day maintenance dose, for a median treatment duration of days [ ] [ ] [ ] [ ] [ ] [ ] . therapeutic management (invasive and non-invasive ventilation, nutrition support) and clinical outcomes (death, length of stay) were similar between groups. there was no difference in potential caffeine adverse effects between groups or within the caffeine exposed group pre and post-caffeine administration. conclusion: caffeine treatment of bronchiolitis related apnea seems to be a standard practice in our picu. our study failed to show any influence of caffeine on clinical outcomes in this indication when compared with a small number of patients. further studies are needed to assess the efficacy and safety of caffeine treatment in this indication as well as the appropriate treatment regimen as pharmacokinetic data suggest that higher dose could be of great interest in this non-prematurely born population. introduction: during the last decade, many authors have raised awareness concerning the increasing rate of venous thromboembolism (vte) in critically ill children [ ] . the presence of central venous catheter (cvc) is one of the most important risk factor for venous thrombosis in children [ ] . the purpose of this study was to analyze incidence and risk factors for catheter-related thrombosis in children admitted in our pediatric intensive care unit (picu). patients and methods: all children aged less than years, admitted in the picu from january to june , and receiving at least one tunneled cvc, were included in our retrospective study. those with venous thrombosis unrelated to cvc placement were excluded. catheter-associated venous thrombosis (cavt) was confirmed using doppler ultrasonography. introduction: weaning from the ventilation is a crucial moment in the icu stay. because of the risks of mechanical ventilation (mv), such as ventilator-associated pneumoniae, it is recommended to begin the weaning process as soon as weaning criteria occurs [ ] . however, extubation is also a hazardous period, with to % of subsequent respiratory failure requiring reintubation, harboring a dismal prognosis [ ] . international guidelines display the criteria triggering the extubation. nevertheless, the physician in charge eventually takes the decision to extubate. in this regard, there could be variations from an individual to another. the main goal of our study was to identify the perceived impediments to mv weaning among physicians, from intubation to extubation. patients and methods: prospective single center study in a bed university icu. all patients admitted between february and may and undergoing mv were included. we daily registered the existence of the criteria recommending a spontaneous breathing trial (sbt), the occurrence of a sbt, the items recommending postponing extubation, and the occurrence of an extubation. the estimated reasons for all the aforementioned decisions were asked to the physician in charge. results: patients were included, gathering days of mv and sbt. the average duration of mv was . ± . days. there was one extubation failure requiring reintubation. there were sbt failures. in cases, sbt was a success but did not lead to extubation because of hypotonia, weak cough, subsequent respiratory failure, hemorrhagic bronchial secretions, hemodynamic instability, absence of weaning criteria, drowsiness (all the aforementioned n = ), post sbt hypercapnia (n = ). out of the sbt ( %) were done while one or several weaning criteria were absent. impediments to weaning trials were different according to the time lag since icu admission, with fluid overload, muscular weakness and persistent need for assist control ventilation settings being the most frequent reasons advocated after days (figure). no objective assessment of muscular or cough strength was performed at any time, neither was monitored the rr vt, vital capacity or inspiratory pressure. . % of patients had otolaryngologist follow-up. the overall mortality of the studied population was . % including mortality related to tracheostomy in patients. the tracheostomy for extended mechanical ventilation was significantly associated with an increase of mechanical ventilation duration before tracheostomy (p < . ), duration of mechanical ventilation (p < . ), length of stay in intensive care unit (p < . ) and mortality rate (p = . ). introduction: acute renal failure complicating surgery has a particularly harmful prognosis, with a mortality of % to %. this high mortality rate is attributed to patient-related factors, the severity of the disease and the type of surgery, but not to the acute renal failure itself. the aim of our study is to elucidate the prognostic factors of acute renal failure in the postoperative sepsis in a series of patients. it is a retrospective analytical descriptive study spread over a period of years (from january to december ), observations of postoperative peritonitis were collected in the service of resuscitation of surgical emergencies of chu ibn rochdof casablanca. the statistical analysis was carried out using the spss software. the results are expressed with or and % confidence intervals (ci at %). the results were considered significant when p is < . . the mean age of the patients was ± years with a sex ratio of . ( m ) . renal failure was the most frequent failure after hemodynamic failure, patients were oliguric, anuriques and patients had a preserved diuresis, patients were divided according to the rifle (r %, i %, f %) and akin (i %, ii %, iii %). the predictive factors of acute renal failure ari were studied in univariate and multivariate analysis, factors were retained including catecholamines-or . + ci at % between . and . + p = . + the surgical site-or . + ci at % between . and . + p = . . conclusion: acute renal failure is an independent factor of mortality in the post-operative sepsis, but remains that its presence is a pejorative prognostic factor. this was a retrospective study performed in a large university hospital. all patients receiving the molecule were included in the analysis. indication for sodium lactate, dose, and modality of administration were collected. we also collected clinical and biological variables before sodium lactate infusion, after h (h ), and after h (h ). an analysis of the evolution of these variables at h and h was performed. results: between january and may , patients, aged years, % males, sofa score [ - ], received an infusion of molar sodium lactate ( ml ). main indications for sodium lactate were hyperchloremic metabolic acidosis ( %), vascular filling ( %), mixed acidosis ( %), and intracranial hypertension ( %). % of the patients presented with a chloride sodium ratio > = . at basal time. sodium lactate was associated with a significant increase of mean arterial pressure at h (p = . ) and h (p = . ), a decrease of catecholamine dose (p = . ) and heart rate (p = . ) at h , and an increase of diuresis in the h period following initiation of the treatment (p = . ). we observed an increase of ph, bicarbonate, base excess, and sodium, at h and h (all p < . ). plasma lactate concentration was increased at h (p < . ), but was not different from basal value at h (p = . ). there were no significant variation of plasma chloride. chloride sodium ratio was significantly reduced. plasma sodium > = mmol l and ph > = . at h were observed in % of the patients. this retrospective study reports the largest number of critically ill patients having received sodium lactate. hemodynamic effects observed in this study are concordant with the data of the literature. the metabolic effects observed in this study, with rapid increase of ph, bicarbonate, and base excess, strongly suggest the potential interest of sodium lactate among critically ill patients presenting with acidosis and increased chloride sodium ratio. introduction: acute kidney injury (aki) is a frequent and severe condition in intensive care unit patients that may require renal replacement therapy, most frequently continuous renal replacement therapy (crrt). although hypoglycemia is a well-known complication of crrt using glucose free solutions, euglycemic ketoacidosis (eka) has never been described in this setting. patients and methods: all anuric patients with glucose free crrt solution induced eka (february -may ) were prospectively included and evaluated. ketoacidosis was deemed possible when nonlactic metabolic acidosis did not improve in patients on crrt. because all patients were anuric, we measured ketonemia and used urinary test strip in the effluent fluid. eka diagnosis was retained when arterial serum bicarbonate was < meg/l despite crrt, in the absence of lactic acidosis and in the presence of ketones in the serum or crrt effluent fluid. results: eighteen patients ( % of our patients under crrt in this period) developed eka during crrt using glucose free solution (phoxilium ® ). time between cvvhdf initiation and ketonemia detection was ( - ) days. patient characteristics are presented in the table . half of them had for a medical history of diabetes ( insulindependent). only patients were receiving insulin and most of them had low glucose or food intake. increasing glucose intake and insulin infusion resolved ketonemia in all cases. discussion: we describe for the first time the occurrence of euglycemic ketoacidosis in critically ill patients under crrt using glucose-free replacement solution. common features of the patients were multiple organ failure with anuria, normal glycemia without insulin infusion and low glucose infusion or food intake. critical illness-induced insulin resistance and starvation could altogether contribute to ketoacidosis even if acidosis is unusual in starvation ketosis. by removing substantial amounts of glucose from the blood, crrt with glucose free solution could worsen this condition, mask hyperglycemia and induce euglycemic ketoacidosis. in critically ill patients on crrt using glucose free solution, euglycemic ketoacidosis is common and should be detected, especially in patients with low glucose intake, no insulin infusion and unexplained metabolic acidosis. importantly, the diagnosis can be missed in anuric patients with normal blood glucose and in the absence of known diabetes. since, cvvhdf-induced ketoacidosis may contribute to persistent acidemia and its adverse effects, serum or crrt effluent fluid ketone level should be measured in this setting. . - ] years. main reasons for admission were hypercalcemia (n = ( . %)), followed by acute encephalopathy (n = ( . %)). median saps ii and sofa scores were [ . - . ] and [ ] [ ] [ ] [ ] [ ] respectively. main causes of hcm were hematological malignancies (n = ( %)), solid tumors (n = ( %)), iatrogenic events (n = ( %)) and endocrinopathies (n = ( %)). median calcium levels at admission, at day and at icu discharge were . [ . - . ], . [ . - . ] and . [ . - . ] mmol l respectively. more than half of the patients (n = ( %)) recovered from hcm days after icu admission. acute kidney injury occurred in ( %) patients and ( . %) patients required dialysis. neurological complications concerned ( . %) patients, mainly delirium (n = , . %). digestive events occurred in ( . %) patients. cardiovascular events concerned ( %) patients and consisted in de novo hypertension in ( %) patients, and ekg disturbances in ( %) patients. during icu stay, ( . %) patients required mechanical ventilation and ( . %) patients required vasopressors. volume resuscitation with crystalloids was the first treatment in ( . %) patients, ( . %) received bisphosphonates and ( . %) received corticosteroids. respective icu and hospital mortality were . and . %. there was no correlation between the degree of hcm and icu mortality (p = . ). icu and hospital mortality were associated with the underlying disease (hematological malignancies (p = . )). conclusion: hcm is associated with high mortality rates. the increased mortality is a consequence of the main mechanism, mainly underlying malignancy rather than hcm per se. the course of hcm may be complicated by organ failures that are most of the time reversible with early icu management. introduction: sepsis is one of the leading cause of death among patients with chronic kidney disease (ckd). the mechanisms of this higher mortality remain poorly understood. sepsis and chronic kidney disease are both conditions associated with a higher plasmatic concentration of bile acids. the farnesoid x receptor (fxr) is a key regulator of the bile acid metabolism and has recently been involved in the regulation of the inflammasome during sepsis. we explored the role of fxr in the prognostic of sepsis in an animal model of ckd. patients and methods: sepsis was provoked by the injection of . mg kg of lps weeks after the creation of ckd. the ckd was created by unilateral nephrectomy associated with contralateral thermocauterisation. the mice (c bl j) were randomly assigned to one of the following groups-sham placebo, ckd placebo, sham lps or ckd lps. a fifth group of ckd lps mice received a treatment with sevelamer (a bile acid sequestrant) during weeks. survival of the animals, serum biochemistry and molecular biology in the kidney were performed after sacrifice. results: whereas the sham lps animals survived, all ckd lps animals died during the h following the injection of lps. the plasmatic urea, il beta and tnfa concentrations increased with the creation of ckd (ckd placebo versus sham placebo animals) and with the creation of sepsis (ckd lps versus sham lps groups). whereas the expression of fxr rna did not changed with the injection of lps in the sham animals (sham lps versus sham placebo), the fxr rna decreased with the creation of sepsis in the ckd animals (ckd lps versus ckd placebo groups). the ckd animals treated with sevelamer weeks before the administration of lps (ckd sev lps group) had a lower plasmatic concentration of il b, tnfa and increased the rna expression of fxr in the kidney compared to the ckd lps group. also, the treatment with sevelamer improved the survival of the ckd lps animals. conclusion: our study demonstrates a relation between fxr and the prognostic of sepsis in ckd animals. the exact link and the potential therapeutic interest of targeting fxr and bile acids metabolism in ckd patients remain to be studied. introduction: dysnatraemia, dyskalaemia and hypomagnesemia are frequent metabolic disorders in intensive care, and their causes represent a major concern for the intensivist, especially in urgent conditions. in the diagnostic approach, we often use the urine analysis. although measurement of -hour urine electrolyte excretion ( -hu) is considered the most reliable method, the great burden and difficulty in collecting complete -hour urine has prompted the search for more practical methods, such as spot urine analysis. the aim of the present study was to compare electrolyte excretion in urine samples collected over different time periods, in comparison with a -hour urine sample collection considered as the gold standard method. patients and methods: this prospective and descriptive study included patients admitted in a tunisian medical icu, between september and december . baseline characteristics, medications and laboratory data including electrolytes and renal function parameters were obtained from all patients. multiple urine specimens for analyzing na + k + mg + urea + ca + phosphate + creatinine + proteins and uric acid were obtained from -hour, -hour and -hour urine samples during day and night time, and results were compared with those obtained from the gold standard method ( -hour urine collection). correlation analysis was performed using the spearman test. results: significant correlation was found for all biochemistry parameters between -hour urine results and those obtained from -hour and -hour samples regardless of day or night sampling. a comparative analysis for sodium and potassium is shown in fig. . conclusion: determination of electrolyte excretion from urine samples taken over different time periods, and h, provides a reliable estimation of -hour urine electrolyte excretion. it appears practical for early understanding of the mechanism of electrolyte imbalance. however, further studies are warranted to confirm the usefulness of this approach. use of the procalcitonin assay in an adult emergencies department: retrospective experience of a general hospital of the suburb of paris ( . - . ). other markers of infectious were poorly recorded (fibrinemia in ( . % + . g l [ . - . ] + immature forms on blood count- . %). only ( . %) had blood cultures in the ed ( patient [ ] [ ] ) and ( . %) other(s) microbiological sample(s), mainly urinary ( patients [ . % + among them % considered as positive]). % of blood cultures were positives, mainly for gram negatives ( %). final diagnosis in the ed was considered as infectious disease (id) in only patients ( . %, including sepsis and septic shocks). ( . %) was considered as non-infected (nid) and final diagnosis remains unprecise in ( . %). pct values was of . ( - . ) in the id vs. ( - . ) in the nid (p < . ), wbc was of . in the id vs. . in the nid (p < . ) and crp was of ( . - . ) in the id vs. ( - ) in the nid (p < . ). no correlation was observed between the pct value and admission to dechocage room admission. . identification of the involved drug was obtained in % of the cases, based on qualitative screening. management was mainly supportive and included sedation ( %), naloxone ( %) and flumazenil ( %). tracheal intubation was required in patients ( . %). one cardiac arrest but no death occurred in the ed. forty-three patients ( %) were transferred to the intensive care unit. conclusion: our dataset provides an interesting insight into the drugs involved in and clinical pattern of toxicity outcome of acute recreational drug toxicity presentations at the ed, despite possible under-declaration and coding. classical recreational drugs were more common ( %) followed by prescription drugs ( %) and nps ( %). and drug ( %) consumers + hiv-infected ( %) and depressive ( %) patients) were admitted to the icu. the main declared compounds were methylenedioxypyrovalerone (mdpv + n = ), -methylethcathinone ( -mec + n = ), -methyl methcathinone ( -mmc + n = ) and -methyl methcathinone ( -mmc + n = ), more frequently used in drug mixtures sold as bath salts or in poly-intoxication with conventional illegal drugs (mainly cocaine and gamma-hydroxybutyrate). nps was used in a recreational ( %), chemsex ( %) or solitary practice ( %). binge ( %) and intravenous ( %) self-administration was remarkable. patients presented acute encephalopathy with psychomotor agitation ( %), confusion ( % + glasgow coma score- [ ]), hallucinations ( %), anxiety ( %), seizures ( %), myoclonus ( %) and stereotypes ( %). ecg typically showed sinus tachycardia ( %), qrs qt abnormalities ( %) and atrio-ventricular block ( %). acute cardiac ischemia ( %) and dysfunction ( %), disseminated intravascular coagulation ( %) and multiorgan failure ( results: during the first and the second study periods and patients were respectively admitted in the icu. total micro-organisms density was and . for patients for the first and the second period, respectively (p < . ). acinetobacter spp and pseudomonas aeroginosa were the predominant isolated microorganisms with a respective density of . and . isolates for patients. figure summarizes the patterns of bacterial ecology and resistance in our icu before and after transfer to new buildings, showing a significant decrease in pseudomonas aeroginosa resistance for ticarcillin and ceftazidim, whereas acinetobacter resistant to carbapenems and enterobacteriacae esbl significantly increased. our study suggests that transfer of icu to the new buildings was associated with a decrease of pseudomonas aeroginosa resistance, whereas acinetobacter spp resistance and esbl enterobacteriacae incidence increased. introduction: infections caused by antimicrobial-resistant bacteria (amrb) are one of the main issues in the spectrum of critically ill patients as they are associated with higher mortality, morbidity, and length of stay. thus, an appropriate initial antimicrobial therapy is decisive for better patient outcomes. the aim of the study is to determine the adequacy of first-line antibiotic therapy guided by weekly amrb screenings. patients and methods: a months prospective study was conducted in -bed micu. were included all patients with more than h of icu stay. an amrb screening was conducted upon admission and on weekly basis for all the patients. the choice of antibiotherapy if indicated, was guided by the most recent colonization results. if the patient has received at least one active in vitro antibiotic against the isolated bacteria, the empiric antibiotherapy was considered appropriate. results: patients were included in the study. mean age and saps ii were respectively ± years and ± . the median length of stay was days. ( %) patients were colonized by amrb upon admission. the most frequent isolated microorganisms were-escherichia coli ( %) and klebsiella pneumonia ( %). were assessed hospital-acquired infections (hai)- ( %) in amrb colonized patients and ( %) in uncolonized ones. the antibiotherapy was considered appropriate in infections ( %). out of the colonized patients, ( %) developed hai. ( %) patients had a concordant colonization body site to the infection. of the nosocomial infections, ventilator-associated pneumonias and central venous catheter infections were the most frequent, both at % (n = and n = ) + followed by urinary tract infections % (n = ) and infective endocarditis % (n = ). ( ). overall, the isolates were-extended spectrum betalactamase productrice-enterobacteria ( %), imipenem resistant-acinetobacter baumanii ( %), and multi resistant-pseudomonas aeroguinosa ( %). ni were documented including caused by mdr bacteria and distributed as follows-ventilator acquired pneumonia-vap (n = ), bacteraemia (n = ), vap with bacteraemia (n = ), catheter related infection-cri (n = ), cri with vap (n = ) and catheter-related bacteraemia-crb (n = ). the performance of mdr bacteria-screening in predicting ni was poor with % of sensitivity, % of specificity, . % of negative predictive value (npv), and % of positive predictive value (ppv). nevertheless, the performance of the nasal swab in the prediction of vap was better with % of sensitivity and . % of npv. conclusion: mdr bacteria-screening is useful as it allows to identifying the mdr bacteria-carriers and helps for a rational use of antibiotics in severe ni. however, its diagnostic contribution in the occurrence of ni is poor except the interest of the nasal swab in the prediction of vap owing to its good npv. we aimed at determining the respective weight of these phenomenon and the physiological determinants of the respiratory variations of the ivc diameter. patients and methods: in mechanically ventilated patients (tidal volume- . ± . ml kg of predicted body weight) haemodynamic, respiratory and the intra-abdominal pressure (iap) signals were continuously computerised. cvp, iap and the ivc diameter (transthoracic echocardiography) were recorded during -second end-inspiratory and end-expiratory occlusions separated by s, before and after the infusion of -ml of saline. patients in whom fluid administration induced an increase in cardiac index (picco- ) > % were defined as "responders". the respiratory variations of the ivc diameter, cvp and iap were calculated as the (end-inspiratory-end-expiratory values) mean value. the compliance of the ivc was estimated by the ratio (end-expiratory-end-inspiratory ivc diameter) (end-expiratoryend-inspiratory cvp). results: fluid administration increased cardiac index by more than % ( . ± . to . ± . l min m , p = . ) in patients. the respiratory variations of the ivc diameter predicted fluid responsiveness (area under the roc curve- . ( % ci . - . ), p < . ). before fluid administration, the ratio of changes in ivc diameter over changes in cvp was not different between responders and non-responders ( . ± . vs. . ± . mm mmhg, p = . ). before fluid administration, the respiratory variations of the cvp tended to be higher in responders than in non-responders ( ± vs. ± %, p = . ). the respiratory variations of the ivc diameter were associated with the respiratory variations of cvp (r = . , p = . ) but not with the respiratory variations of iap (r = - . , p = . ). the respiratory variations of the ivc diameter were not explained by a higher ivc compliance but rather by higher respiratory variations of the cvp in responders than in non-responders. interestingly, it seems that iap, the ivc extramural pressure, was not involved in the respiratory variations of the ivc diameter. inclusions are ongoing. during the hospitalization in icu, there was no significant difference between the two groups regarding the proportion of patients with aki through icu discharge. in the intervention group, % of the patients had a glomerular filtration rate lower than ml min . m compared to . % in the control group (p = . ) at day- . we found no significant difference between the two groups neither on hematopoietic effects of epo or serious adverse events. in patients resuscitated from an ohca of presumed cardiac cause, early administration of erythropoietin compared to standard therapy did not confer any renal protective effect. salvetti marie , and the ratio of end-diastolic areas of both the right and left ventricle in the long axis view of the heart (rveda lveda) were measured. a lvef < % defined lv systolic dysfunction, a ci < l min m defined low cardiac output, and a rveda lveda ratio > . (± associated with a paradoxical septal motion in the short axis of the heart) defined rv dysfunction (± acute cor pulmonale). the preload-dependence was evaluated using deltasvc or deltavmaxao. front-line hemodynamic and metabolic parameters were recorded at the time of tee assessment. results: lvef and ci could be simultaneously measured in of patients ( %). patients ( %) had a low ci related to lv systolic dysfunction (lactate- . ± . mmol l), patients ( %) had a low ci and a preserved lvef related to a rv dysfunction or to a sustained preload-dependence (lactate- . ± . mmol l), patients ( %) had preserved ci and lvef (lactate- . ± . mmol l) including only patients ( %) with a hyperkinetic profile (high ci and lvef > %), and patients ( %) had preserved ci but altered lvef (lactate- . ± . mmol l) due to a marked tachycardia. none of the front-line hemodynamic parameters was discriminatory to identify the circulatory profile identified by tee assessment (table) . introduction: aortic end-systolic pressure (esp) is considered as a reliable index of left ventricular afterload. recently, the effective arterial elastance (ea), i.e., the ratio of esp over stroke volume (sv), has also been proposed as a reliable afterload index. our aim was to document peripheral estimates of ea (eapsap) at the bedside in critically ill patients, and to investigate the haemodynamic mechanisms responsible for ea changes after fluid administration (fa). in the validation study, carotid tonometry (complior) was prospectively performed on haemodynamically stable spontaneously breathing patients equipped with an arterial femoral (n = ) or radial (n = ) catheter. ea was defined as the ( . × csap) sv ratio, where csap was the central systolic arterial pressure directly measured from the calibrated carotid waveform. eapsap was calculated as the ( . x peripheral systolic arterial pressure) sv ratio. sv was obtained by transpulmonary thermodilution or transthoracic echocardiography. in the clinical study, we included patients with invasive haemodynamic monitoring (picco- ), in whom fa was planned. results: in the validation study, the complior allowed estimating ea in all patients (ea = . ± . mmhg ml). the (eapsap-ea) bias was smaller at the femoral than radial artery level ( . ± . vs. . ± . mmhg ml, p < . ) and was strongly related to the systolic pressure amplification between the carotid and peripheral artery (r = . , p < . ). ea was more strongly related to sv (r = − . ) than to esp (r = . ) (each p < . ). the four-quadrant plot analysis indicated that patients ( %) exhibited a concordant low ea high sv pattern or high ea low sv pattern, while only patients ( %) exhibited concordant high ea high esp pattern or low ea low esp pattern (p < . ). there was a negative relationship between changes in eapsap and changes in sv in the whole population, in fluid responders (cardiac index increases > % after fa), in pressure responders (mean arterial pressure increases > % after fa) and in non-responders, while no consistent relationship between eapsap and esp changes was documented. conclusion: ea may be reliably estimated at bedside by using the ( . x femoralsap) sv ratio. ea value and ea changes induced by fa were related to sv rather than to esp. thus, ea should be considered as an index reflecting sv rather than left ventricular afterload in critically ill patients. this study included a sham group (n = ), a cpb group (n = ), an ir group (n = ) and a cpb-ir group (n = ). rats were exposed to min of cec, min of left pulmonary ischemia and min of reperfusion. fonctional endothelial dysfunction was evaluated by measurement of the pulmonary artery reactivity. systemic inflammation was evaluated by the plasma assay of il- beta, il- and tnf-alpha. the endothelial glycocalyx was evaluated by plasma assay syndecan- and electron microscopy. the statistics were performed using an anova test, p < . . we showed that cpb associated with ir induce an endothelial vasorelaxation dysfunction mainly mediated by nitric oxyde (no introduction: during circulatory shock, the goal of increasing cardiac output is to correct tissue hypoxia, which can be manifested by an increase in oxygen consumption (vo ) associated with an increase in oxygen delivery. we hypothesized that, in patients in circulatory shock, veno-arterial co gradients (pv-aco ) could be a good predictor of an increase in vo in fluid responders. patients and methods: we included patients with circulatory shock who received a fluid challenge. circulatory shock was defined by the association of vasopressor requirements to maintain mean arterial pressure (map) and a blood lactate concentration ≥ mmol l. we measured cardiac index (ci) and arterial and central venous blood gases and arterial lactate before and after a volume expansion ( ml of plasmalyte ® ). cardiac index (ci) was measured using a pulse contour analysis method (picco + pulsion, munich, germany). ci responders were the patients in whom ci increased (Δci) by > %. in those patients, vo responders were those in whom vo increased (Δvo ) by > %. receiver operating characteristic (roc) curves were performed. the data was presented as median ( th percentile- th percentile). a p < . was considered as statistically significant. introduction: the autonomic nervous system (ans) is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of ans activity and a relation between hrv and outcome has been proposed in various types of patients. while electrocardiographic hrv assessment seems to be the gold standard, we evaluated the feasibility of an automated hrv monitoring based on standard photoplethysmographic monitoring. this project is based on a prospective physiological tracing data-warehousing program (rea stoc, clinicaltrials.gov # nct ) that aims to record more than icu patients over a -years period. introduction: diabetic ketoacidosis is an acute complication of diabetes, defined as metabolic acidosis with a high anionic gap, associating hyperglycemia > mmol l ( g l), positive ketonuria, or superior or equal ketonuria to ++, it is a medical emergency which can occur in a known diabetic patient, or not. objective-to describe the clinical therapeutic and prognostic aspects of diabetic ketoacidosis in the intensive pediatric care unit at the ehs canastel oran, algeria. patients and methods: retrospective study carried out over a period of years. from january , to january , , in the intensive pediatric care service. the data was entered and analyzed using excel . results: cases were retained on hospitalizations per year, % of cases had no history with diabetes, % occurred in known diabetics with insulin, but are not followed medically. our patients were aged from months to years, but the average age of these patients was years and months, with a slight female predominance, coma was preceeded by % of cases polydipsy polyuria syndrome and % weight loss, triggered by an infectious syndrome including % of ent cases, % of respiratory infections and % of cases with digestive infections characterized by fever, abdominal pain, vomiting. the delay between diagnosis and admission to ice was - days. at admission % of patients were scored at on the glasgow scale, with presence of the cough reflex, and % were scored at < requiring tracheal intubation and mechanical ventilation of h with signs of dehydration and ionic disorders, namely hypokalemia and hypernatremia, blood glucose at admission varies between . and g l with glycosuria at +++ and ketonesuria between ++ and ++++ in only % of the patients had metabolic acidosis, a cerebral computed tomography (ct) performed in % of cases found a slight cerebral edema. therapeutic management was the rehydration, correction of metabolic disorders and introduction of insulin into sap, with monitoring and subcutaneous relaying due to ketonuria negativity. the outcome was favorable for all patients. conclusion: diabetic ketoacidosis is a major complication of diabetes which can be avoided by a good prevention campaign and systematic screening of any child suspected of diabetes, recognition of risk situations such as infections and clinical manifestations in order not to delay the management. introduction: scorpion sting is a public health problem world wide with a global distribution of species. in algeria, scorpionic envenomation occupies a prominent place in declarations. in , cases were reported. the objective of our study is to describe the epidemiological, diagnostic, therapeutic and evolutionary characteristics of the scorpion sting in children. retrospective study of cases of scorpionic envenomation hospitalized in the pediatric resuscitation department of the ehs canastel oran conducted during the year the inclusion criteria were the presence of traces with at least one locoregional or general clinical signs. the parameters studied-age, sex, city of origin, time of bite, time of management, initial first aid, time limit for admission to pediatric intensive care, and severity criteria. results: % of these cases were boys and % girls. the mediane age . % of the punctures occurred during the day, the site of the injection was the lower limb in % of the cases and there were bites scorpion cases in the west of algeria and exactly in oran and tiaret. of the cases was the upper limb. the delay of the management was from to h for of the cases who were classified in the third classed according to the clinical signs of gravity. the type of the scorpion was not identified. we can classify all the patients that we received in our service into three classes − % in class i, with local signs such as pruritus, redness, abnormalities and local pain. eva - , calmed by the infusion of mg kg iv of paracetamol and application of xylocaine cream at the site of the sting. introduction: the residence of children in intensive care is most often due to the existence of one or more organ dysfunction which requires heavy treatment (intubation, ventilation, drainage, venous tract) and this in a hostile environment which amplifies the aggression organic. the main objective of our work is to study the consequences of hospitalization of children in pediatric resuscitation. patients and methods: this is a descriptive prospective study on the outpatient consultation file of canastel's ehs multipurpose resuscitation. we studied files and assessed memory, perception of contact and nuisance factors felt by sick children. results: out of children seen in post resuscitation. the sex ratio is . . the average age of children is years ( months- years). the average hospital stay is days. the average gos (glasgow out scale) is . ( ) ( ) ( ) ( ) . the average duration of ventilation is days. % of children had central vascular access. three children describe a total memory of the stay, some memory and none. three children have a good perception about the staff, one child dissatisfied and three others indifferent. the nuisance factors described by the children are pain ( ), cold ( ), noise ( ), hunger ( ) and light ( ) . conclusion: consequences of psychological trauma, insufficiently evaluated especially by the staff, which result in the appearance of psychological disorders (nightmares and anxiety) with sometimes even severe post-traumatic neurosis. hence the need to adapt the environment and mainly noise and respect for sleep. [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the median treatment duration time was at ( - ) minutes. femoral vein was used as vascular access ( %) and most of pe procedures ( %) were performed with citrate anticoagulation. median exchange volume was at [ - ] ml and renal replacement fluid was fresh frozen plasma (ffp) in %, % ffp and % human albumin % in % and human albumin only in % of procedures. adverse effects were observed in less than % of procedures and % were lifethreathening including cardiac arrest, heart rhythm disorders, cerebral oedema and hemolysis. other remaining complications were secondary infections %, hemorrhage %, and pulmonary oedema % in all patients. twenty patients deceaded (icu mortality %). icu and hospital lenght of stay was at ± and ± days respectively. of survived patients still underwent pe after their icu discharge + totally recovered whereas ( %) were on partial remission. conclusion: pe is a routine and feasible technique in icu. this study showed that tpp was the most commonly indication of its use and that outcome was fair. adverse effects frequently occured but most of them were not severe. further studies would benefit form larger cohort to improve indications, delay of initiation and practice of this treatment. renal replacement therapy was required in % of elderly versus % (p = . ). frequency of ttp, hus and ahus was similar beetween groups. tma was more frequently associated with ongoing cancer and drug use in elderly ( vs. %, p < . and vs. %, p < . , respectively). gastro-intestinal bleeding during icu occurred more often among elderly ( vs. % (p = . )). icu mortality rate was higher ( vs. %, p = . ). no difference was found concerning plasma-exchange therapy, steroids use, and rescue treatments for refractory-ttp. discussion: increased complication and mortality rates in the elderly group might be ascribed to more cardiovascular morbidity in this population. the association between tma and ongoing cancer suggests a routine oncological workup among elderly. introduction: neutropenia, defined by an absolute count of polymorphonuclear neutrophils less than < mm , exposes patients to infectious complications that can lead to sepsis or septic shock. the mortality risk is higher. the french guidelines published in were formulated to homogenize the clinical practices and improve survival. we performed a monocentric retrospective study including all consecutive patients admitted to the medical icu of a tertiary hospital to a neutropenia with sepsis or septic shock, between the th of december and the th of december . the study protocol was approved by the local ethics committee ( . ce ) and published on clinical trial (nct ). results: patients were admitted in icu during this period. patients ( %) presented a neutropenia with sepsis or septic shock. among these patients, % had hematologic malignancies and % had solid tumour. patients ( %) was treated empirically with antipseudomonal beta-lactam or carbapenem and aminoglycoside. ( %) skin or suspected catheter-related infections were treated with anti-mrsa (methicillin-resistant staphylococcus aureus), vancomycin or linezolid. adequate antibiotics as described in guidelines was performed to patients ( %). patients ( %) received aminoglycoside ( patients received initial dose in icu, patients complement dose) and ( %) received anti-mrsa with antipseudomonal betalactam or cabapenem. patients ( %) had microbiologically documented infections with, % of bacteria ( % of gram-posit cocci, % of gram-negative cocci, % of gram-negative bacillus), % of fungi and % of viral infection ( table ) . among of them, % ( ) of esbl, % ( ) of mrsa and % ( ) of emerging highly resistant bacteria (bhre). the icu-mortality rate was % ( ) with % of -day mortality ( ). the curves of the cumulative incidence of death risk between d and d were no different according to adequate empirical antibiotic treatment as like french guidelines (fig ) . by multivariate analysis, independent factors of adequate antibiotic treatment were septic shock (or, . + % ci . - . ) and febrile neutropenia > days (or, . + % ci . - . ) at icu admission. conclusion: according to the usual clinical practice, septic neutropenic patients was already treated empirically by bitherapy including antipseudomonal or anti-mrsa if there is a skin or suspected catheter-related infection. adjunction of aminoglycoside in of the symptomatology in case of overdose, make the diagnosis difficult, especially since the drug in question is often unspecified and the toxicological analysis is not exhaustive. introduction: carbon monoxide intoxication is a public health problem in tunisia and around the world. currently, it is unclear the impact of this type of poisoning in our country for lack of declarations. we propose in our work to study the epidemiological characteristics of fatal carbon monoxide intoxications collected in the forensic pathology department of the university hospital in sfax, tunisia, to describe the different steps used in forensic diagnosis of fatal carbon monoxide intoxication and to propose preventive measures to reduce the rate of these intoxications. patients and methods: it is a retrospective study of cases of fatal carbon monoxide intoxications collected in the forensic pathology department of the university hospital in sfax, tunisia during years ( january to december ). commemoratives were collected from medical and police records. a forensic autopsy and a toxicological analysis were carried out in all cases. results: fatal carbon monoxide intoxication is the leading cause of toxic death in sfax during the period of our study. we notice a decrease in the incidence of this type of intoxication. the average age of deaths was years and months with male predominance. the peak frequency of intoxication was in cold season. the most frequent form of intoxication was accidental. the source of carbon monoxide was mainly the defective water heater often placed in poorly ventilated areas. the classic carmine red-color of lividity was found in the majority of cases. myocardial distress, favored by hypoxia, has been reported in two subjects with a pathological coronary artery. the mean hbco level was . %. however, account must be taken of the survival time and the time elapsed between death and dosing of hbco. the incidence of fatal carbon monoxide intoxication has decreased since and the victim profile has not changed too much. the fatal carbon monoxide intoxication is still persists as a public health problem in tunisia. the reduction of its frequency requires the implementation of a well-structured prevention plan based on epidemiological data from a national registry. the identification of these data requires mandatory reporting of this type of intoxication in tunisia. introduction: olanzapine is an atypical antipsychotic drug frequently prescribed in the treatement of bipolar disorder and schizophrenia. acute poisoning with this molecule is rarely reported. through this study we aimed to evaluate the incidence and describe the different clinical features of acute olanzapine poisoning. patients and methods: retrospective analysis of all cases of olanzapine intoxication admitted in -bed teaching icu between january and decembre . inclusion criteria were patient age ≥ year, acute olanzapine intoxication, the intoxication severity was assessed by the poisoning severity score (pss) of the european association of poison centres and clinical toxicologists. the evaluation of electrocardiograms was performed in the first day of hospitalization. the durations of qrs and qtc was measured and arrhythmias and conduction disorders was identified. results: patients were included, the mean age was ± years. they were males and females. long term treatment with olanzapine was noted in patients ( %) who suffered from psychiatic desease. the supposed ingestion dose ranged from to mg. the mean consulting time was ± h after the ingestion. olanzapine was co-ingested with others drugs in patients ( %). co-ingested drugs were-benzodiazepine (n = ), levomepromazine (n = ), serotonin recapture inhibitor (n = ), amitriptilyne (n = ) and biperiden (n = ). the pss was moderate in cases ( . %), severe in cases ( %) and fatal in case. the main clinical signs were tachycardia and miosis in % of cases each of them (n = ), agitation in % of cases (n = ). ecg abnormalities has been detected such as prolonged qtc in cases with a mean duration of ± ms. in the group of monointoxication ( patients) the pss was moderate in cases ( . %), severe in cases ( %) and fatal in one case. the coma glosgow scale was < fig. kaplan-meier survival between admission and -day according to adequate empirical antibiotic therapy guidelines (log rank, p = . ) in cases. mechanical ventilation was required in % of cases (n = %) with a mean duration of ± heures. the mean duration of icu stay was of ± h. twenty three patients recovered during the hospitalisation, one patient died with severe poisoning. conclusion: as showed in this study, acute olazapine poisoning could be severe, and lead to death sometimes. introduction: voluntary drug intoxication (vdi) continues to be a major health problem in many developed and developing countries. in algeria, this has become a worrying concern. awareness-raising is launched to prevent the public from these dangers. vdi are intentional or rarely accidental and can be individual or collective and affect all age groups. the vdi represents the first reason for hospitalization in the emergency department university hospital of oran. in algeria there is no national or regional register of voluntary intoxication. knowledge of the causes of drug poisoning should therefore be extrapolated from foreign studies. to draw up an assessment of the imvs, a retrospective study was carried out over the years ( - ) . this survey consisted of collecting data on the nature of the drug, age, sex, major toxidromes, severe imvs requiring hospitalization in icu, mortality, e.t.c scores and glasgo scores. results: cases of acute poisoning were collected, with a predominance in patients aged between and , a percentage of . %. in addition, most patients were female with . %, a sex ratio of . with p < . . the main toxidromes were-opioid syndrome in % of cases and anticholinergic syndrome in % of cases. etc with a score of > % accounted for % of patients. severe vdi requiring resuscitation hospitalization were %. conclusion: acute poisoning remains high and steady in the oran region and the under- age group represents the most affected category. awareness campaigns must be launched throughout the year to better conserve and store medicines, phytosanitary products and other chemicals. improved socio-economic conditions would help to reduce voluntary intoxication. introduction: scorpionic envenomation is unevenly distributed throughout the world and is particularly frequent in some regions of the world, notably north africa. the purpose of this work is to describe the epidemiological profile of the scorpionic envenomations admitted to the resuscitation department of mahres. patients and methods: a prospective study conducted at the mahres intensive care unit over a period of months ( until ), including all patients admitted for scorpion envenomation. results: we collected cases of patients admitted to the resuscitation department of mahres from to , including cases of scorpionic envenomations, i.e. . %. the median age was years with extremes ranging from to years. the sex ratio was . scorpion stings occurred at night in % of patients, % in the first half of the night (between pm and - pm) and % in the second half of the night ( to h). venom inoculation points were in the lower limbs in % of cases, followed by upper limbs ( %). the color of the incriminated scorpion was yellow in %, black in % and unspecified in % of the cases. for admission classes, there were % class i, % class ii and % class iii. the traditional therapeutic gestures practiced by the patients or their entourage were the laying scarification ( %) and the suction ( %). all patients received anti-scorpion serum, an analgesic, serum and tetanus vaccine. the progression was favorable in all cases after an average hospital stay of ± days. conclusion: scorpionic envenomations are indeed a reality in mahres with a non-negligible frequency despite under-reporting of cases treated by traditional medicine or in other hospitals. they mostly affect young people and the associated clinical manifestations often remain benign. introduction: severe pediatric poisoning is defined by the need for intensive care monitoring due to the nature, quantity of the substance and or clinical manifestations. it is one of the frequent reasons for admission to emergency and resuscitation. the purpose of this work is to identify poisoning in children admitted to pediatric intensive care units in order to assess the frequency, identify the products involved, and the clinical and evolutionary aspects. patients and methods: this is a descriptive study over a -month period in the canastel oran multi-purpose pediatric intensive care unit from july to july . we included all children aged - years admitted for ingestion and inhalation of products toxic. results: children admitted to pediatric intensive care, mean age was years, % under years with extremes of months and years, a female predominance of % was observed with a slight predominance of accidental poisoning ( %) compared to voluntary poisoning ( %). in % the toxic is ingested orally. the most frequent toxicants were drugs with cases ( %), mostly antidepressants and antiepileptics, followed by organophosphates with cases ( %), co cases ( %), petroleum products and plants with cases ( %). the main clinical signs were neurological signs ( %) with predominance of coma and convulsions in cases ( %), respiratory distress was present in cases ( %) and digestive signs cases ( %). for therapeutic management gastric lavage, charcoal and antidotes were the most frequent treatments. the evolution was marked by a mortality of % or a death secondary to a poly-medicinal intoxication voluntary in a girl of years. mechanical ventilation in cases ( %) and an average hospital stay of days. conclusion: acute poisoning is a medical emergency that may require resuscitation. young children are most exposed with drugs are the most frequently incriminated. we propose, as a preventive measure, companions of information on the dangers of toxic products and especially of medicines by the surveillance of the child and the regulation of certain products. introduction: the place of neuron specific enolase (nse) dosing remains uncertain as an indicator of neurological prognosis after a cardiac arrest, the threshold value for predicting an unfavorable evolution being variable from one study to another. our objective was to determine a nse cut-off value predictive of poor neurological outcome after a cardiac arrest. patients and methods: we realized a monocentric prospective trial in a medical icu of a french university hospital from january st to december th . all patients over years old hospitalized for a cardiac arrest in medical icu were included. patients who died during the first h or admitted for cardiac arrest with a neurological cause were excluded. serum nse values (elecsys nse test, cobas ® analyzer) were assessed at h and h after cardiac arrest. somatosensory evoked potentials were recorded between h and h . the primary endpoint was neurological outcome at month using the cerebral performance category scale (cpcs). cpcs or was considered as favorable outcome and cpcs higher than as poor outcome. data were collected using cardiologic or neurologic consultations report, or by phone call to the patient. using a roc curve we determined the nse value at h with higher specificity and acceptable sensitivity. results: we included patients. average age was years old. noflow time and low-flow time were respectively . and min. hypothermia was performed in ( %) patients. patients ( %) died in the icu. the -day and -months survival rates were respectively and % with a favorable outcome of % at months. on the roc curve we found a cut-off value of ng ml with specificity of . ci % ( . - . ) and a sensibility of . ci %( . - . ). area under curve was . ci % ( . - . ). out of the patients with a rising nse between h and h had an unfavorable outcome. among patients with nse > ng ml, the cortical n responses were bilaterally present in of them. conclusion: in our study nse value over than ng ml at h was predictive of poor neurological outcome after cardiac arrest. nse may prove to be a useful marker in patients with present n responses, possibly limiting the duration of hospitalization by introducing therapeutic limitation or withdrawal of support. physicians assessment of prognosis in icu patients with brain introduction: outcome prediction in icu patients with severe brain damage is a difficult task with observed heterogeneity in physicians estimation. the aim of the survey was to evaluate the prognostic estimates and treatment recommendation of intensivists in real patients with various causes of severe brain damage. patients and methods: a web anonymous survey including a summarized clinical report of four patients who stayed in the icu was submitted to french intensivists. patient presented with prolonged hypoglycemic coma, patient with intracerebral hemorrhage, patient with central and extra pontine myelinolysis, patient with a brainstem hemorrhage. all these patients received full treatment in the icu and had a -month follow-up. physicians were provided with the four clinical vignettes including clinical history, brain imaging and other relevant exams (csf, eeg,…), evolution of symptoms within the first days of the icu stay. they had to estimate -month outcome using modified rankin scale (mrs) where a score from to was considered as a good outcome and to as a poor outcome. they had to provide a recommendation about care among the following-full treatment, care limitation, care withdrawal. results: physicians completed the survey. there were ( . %) female. ( %) respondents were residents and ( . %) had a > -year of experience. patients and had a good -month outcome with mrs and mrs respectively while patients and had a poor outcome, both with mrs . correct prognosis estimations were ( %), ( . %), ( %) and ( . %) in patients to respectively. care limitation or withdrawal was recommended by ( . %), ( . %), ( %) and ( %) respondents in patients to respectively. of interest, care withdrawal was recommended by ( . %), ( . %), ( . %) and ( . %) respondents in patients to respectively. univariate analysis did not display any factor related with a good prediction of prognosis. conclusion: in this study, overall predictions were pessimistic with important variations among respondents. although decisions to withdraw life sustaining care were relatively low with regard to estimated prognosis, both inappropriate care limitation leading to self-fulfilling prophecies and unreasonable prolonged life supportive care could result from these estimations. introduction: organ harvesting is a national priority because of the shortage of organs, responsible each year for the lengthening of transplant waiting lists. among the identified potential donors, the main cause of non-harvesting is the refusal of organ donation (od), which exceeds % in france and % in paris area. patients and methods: in a network of hopitals, each procedure on a potential donor by the donor co-ordinator is recorded in a report. after selection of the reports with interviews with relatives about od between and , the data in the reports were collected and a multivariate logistic regression was performed to identify the factors associated with the refusal. results: reports with interviews about od was found. the overall opposition rate is . %. among the children ( . % of cases) the opposition rate is . %. among adults, ( . %) expressed their will about od during their lifetime, with an opposition rate of . % and for the ( . %) of them who never expressed their will, the opposition rate is . %. the factors associated with opposition in multivariate analysis are presented in table . when the deceased had never expressed their will, the reasons given by the relatives to justify the refusal are specified in . % of the reports. these are religious grounds ( %), cultural grounds ( %), respect for physical integrity ( %). in % of the cases, relatives believe that the deceased would have been opposed, and in % of the cases, they choose to refuse because they do not know the deceased's opinion. discussion: french law is based on presumed consent. despite this, it is noted that when patients had never expressed their opinion about od (and therefore had not refused it), the opposition rate reached . % and was comparable to the patients who had expressed themselves. conclusion: in our study, factors related to refusal of od are mainly related to the characteristics of the deceased (religion, culture, history of ethylism) and those of relatives (disagreement, presence of a spouse), but little to the way of doing the interview. however, there is a trend for less opposition when the interview is conducted during the day (between - and - ). on the other hand, when relatives first address the issue of od, the opposition rate is lower. introduction: french intensive care society guidelines and the claes-leonnetti law recommend that intensive care teams organize collegiate and multidisciplinary discussions regarding limitation and withdrawal of care decisions. these moments, coined ethical staffs in our unit, require freedom and safety of speech, which can be difficult to obtain when people are caught in hierarchical and or power relations. we sought to assess the representations, perceptions and opinions of icu personnel regarding ethical staffs. patients and methods: a questionnaire, developed by the icu psychologist, was distributed to the entire unit (secretaries, nurses, nursing auxiliaries, doctors) over a period of months. this -question questionnaire covered session organization and power relations between participants. results: among the questionnaires distributed in the icu, were retrieved and analyzed. medical function was associated by respondents with roles linked with power (leading, knowledge, decision, explanation) whereas paramedical function was associated with roles linked with care (perception, account, spokesperson) (fig. ) . regarding representations of decision making, nurses were considered as decision makers in cases ( %) and doctors in cases ( %). discussion: although ethical staffs are presented as a place where each opinion counts, stereotypes representation appear in the different roles assigned-on one side doctors are in charge of explanation and decision, and on the other side, nurses are taking care of patient's feelings and assume a role of spokesperson. these stereotypes correspond to gender stereotypes assigning women to positions of care, empathy and relationship, and men to more intellectual and leading skills. these gender stereotypes attest a hierarchy internalized by each one, as highlighted by social sciences and gender studies. conclusion: our results highlight the existence of a global idea, shared by the majority-doctors are decision makers and therefore are in a power relation regarding paramedical staff. this hierarchical relationship persists in this moment wished egalitarian (each opinion would count equally). these is a linkage between professional power relations and gender power relations, which show an association between doctor and masculine "qualities" and caretakers and feminine "qualities". these power relations are rarely acknowledged but could have a significant impact on the decision process of these meetings, and should be further investigated. results. despite the diary, % had a qspt score > , indicating a higher post traumatic disorders. patients ( %) presented a anxiety score > and patients ( . %) had a depression score > . these results underline the need of psychological support after the stay. conclusion: many survivors of intensive care unit reported a high level of psychological distress. it seems important offer at this patient a psychological support after an intensive care unit stay. most patients needs return in intensive care unit to understand some elements of hospitalization. actually, this support lack to screening and treatment this psychological morbidity. prevalence and description of the complications following a percutaneous coronary intervention for a myocardial infarction in non-cardiac critically ill patients: a retrospective single-center introduction: type myocardial infarction (mi) is an emergency, which immediate invasive strategy by a percutaneous coronary intervention (pci) is based on guidelines for cardiologic patients. conversely, the invasive strategy remains uncertain for patients hospitalized in the intensive care unit (icu) for a primary non-cardiac disease with mi as a complication, given the ischemic and hemorrhagic risks. we aimed to assess the prevalence of-and describe the major adverse cardiac and hemorrhagic events occurring in the icu after an invasive strategy by pci in this context. we conducted a retrospective single-center -year ( - ) study. all the consecutive icu patients with a suspected mi undergoing a coronarography were screened. patients treated with an invasive strategy (pci performed within days of mi) were included. patients hospitalized in icu for cardiac disease were excluded. the major adverse cardiac events (mace) were defined as post-procedure events occurring in the icu, including death from cardiovascular causes, mi recurrence, need for emergent revascularization and stroke. the major adverse hemorrhagic events (mahe) were defined as post-procedure events occurring in the icu, according to the bleeding academic research consortium. results: icu patients suspected of mi underwent a coronarography. patients ( %) had significant coronary lesions. twelve patients were excluded-tri-truncular coronary involvement (n = ), delayed procedure (n = ), cardiogenic shock (n = ). patients were included ( men, years [iqr - - - ], patients mechanically ventilated, patients with sepsis septic shock, median sofa score at the time of mi [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ). a pci was performed during the first day after diagnosis of mi in patients ( %) (median time- day [iqr - - - ]). a mace occurred in patients ( %), including stroke (n = ) and mi recurrence without revascularization (n = ). no patients deceased from cardiovascular causes in the icu, neither at months post-procedure (table ) . a mahe occurred in patients ( %), of whom had a mace. altogether, the prevalence of major adverse cardiovascular events combining mace and mahe was . ( % ci . - . ). there was no difference between septic and non septic patients regarding the prevalence of mace or mahe. the prevalence of adverse cardiovascular events after an invasive strategy by pci is high in non-cardiac critically ill patients with mi. larger studies are needed to determine which patients may benefit from this procedure. introduction: resuscitated cardiac arrest (ca) lead to immune alteration including lymphopenia, decreased monocyte hla-dr (mhla-dr) expression and dysregulated production of cytokines. in a recent multicenter randomized clinical trial, we tested the hypothesis that cyclosprine a (csa) would limit organ failures following out-of-hospital cardiac arrest (ohca). in a substudy, we aimed to determine the influence of csa on ohca-induced immune dysfunction. this study is a predefined substudy of the randomized cyrus trial (cyclosporine in ca resuscitation). patients with non-shockable ohca randomly received either an intravenous bolus injection of csa ( . mg kg) at the onset of advanced cardiovascular life support (csa group) or no additional intervention (control group). patients from the coordinating center were sampled at admission (d ) and at h (d ). complete blood count, cd + lymphocytes count and mhla-dr were evaluated by flow cytometry. serum levels of il- , il- , il- , il- and tnf&# + were measured by elisa test on frozen samples. results: a total of patients were sampled- patients from the csa group and from the control group. the characteristics of the patients, including resuscitation data, were also similar between the two groups at admission. the severity of organ failure as assessed by the sofa score at admission was similar between groups. all patients introduction: critically ill patients experience major insults that lead to increased protein catabolism and a significant loss of lean body mass with an impact on weaning from the ventilator and muscle recovery. in critically ill patients, severe and persistent testosterone deficiency is very common after icu admission. administration of testosterone may induce skeletal muscle fiber hypertrophy and decreases protein breakdown. the aim of this work is to assess testosterone levels in critical ill patients and to evaluate the safety of testosterone gel administration. this is a single center study realized in a university icu of beds. total testosterone levels were measured in critical ill men with at least one organ dysfunction with sofa > . the study drug was androgel, a formulation of % testosterone in an alcohol-water gel, approved by the ansm for treatment of hypogonadism in men. androgel was applied to the abdomen, shoulders or upper arms once a day at the same time to dry and intact skin during icu stay. the daily dose was mg in men and mg in women daily. patients with history of prostate or breast cancer or psa > ng ml were excluded. results: total testosterone levels were measured in men. median length of stay at the time of measurement was days in icu and days in the hospital. plasma testosterone levels were low in all but patient. median testosterone level was ng dl (normal values - ng dl). testosterone levels were not correlated with score sofa or length of icu stay. we found a moderate positif correlation between testosterone levels and length of hospital stay (r = . =). testosterone gel was administered in men and in women. in these patients, the median score sofa was , icu death occurred in patients ( % icu mortality), median length of ventilation was days and median length of stay in icu days. all patients received mechanical ventilation and vasoactive treatment. patients needed renal replacement therapy. androgel was well tolerated. no ischemic cardiovascular events were described. there was no application site reaction or acne. median length of testosterone gel administration was days. conclusion: critical ill patients have low testosterone levels. testosterone gel may be safely administered during the acute phase in icu. randomized clinical trials are needed to evaluate the impact of testosterone gel on physical performance. introduction: stroke is the leading cause of physical disability and the second leading cause of death worldwide. two thirds of all strokes occur in developing countries and is increasingly a public health problem. the aim of this study was to evaluate the epidemiology of strokes in oran, algeria in order to create a stroke registry. patients and methods: a cross-sectional study was conducted on all patients admitted for stroke at the oran chu between january and september . sociodemographic data, modifiable and nomodifiable risk factors, type of stroke, degree of disability, severity scores (glasgow and nihss) were studied. the spss software, log rank test, was used for data analysis and statistical testing as well as kaplan-meier for survival studies. results: a total of stroke patients were enumerated, aged - years (mean ± sd = . ± . ), . % had an ischemic stroke and % had a haemorrhagic stroke. % of the patients were men and % of the women. high blood pressure, diabetes, emboligenous heart disease and smoking were the most common risk factors. intra-hospital mortality was . % and the overall survival rate at days was %. conclusion: this epidemiological study demonstrates that strokes at oran hospital may be similar to other locations. however, it seems necessary and useful to design a continuous patient registration system. introduction: the prevalence of hyperosmolar states and the relationship with mortality nevertheless remain unquantified and not objectively demonstrated. the aim of this work is to determine whether hyperosmolarity is a prognosis factor, and to assess the impact of hyperosmolarity on the evolution of patients. patients and methods: this is a retrospective descriptive and analytical study performed at the medical intensive care unit at the university teaching hospital ibn rushd in casablanca on the cases admitted during year. we noted epidemiological, clinical, biological and evolutionary parameters of all the patients and divided them into two groups according to their osmolar states, the first non-hyperosmolar group with plasma osmolarity of less than mosm l, called the control group and the second hyperosmolar group, plasma osmolarity greater than or equal to mosm l. results: patients were included. the first group comprised patients ( %) and the second comprised patients ( %). the two groups did not differ significantly about sex and age. hyperosmolar patients had more diabets . %. patients in the two groups did not show significant differences in clinical outcomes, including apache ii and saps ii scores. significant differences are reported between the two groups, in natremia, creatinemia, liver transaminases. the plasma osmolarity was significantly different between the two groups with a mean in the control group of . ± . mol l while in the hyperosmolar group it was . ± . mosmol l (p = . ). the prevalence of hyperosmolar states in the study was % with % mortality. in the control group % were intubated-ventilated + . % received vasoactive drugs and . % received antibiotic therapy. in the control group + %of the patients were complicated by nosocomial infection, . % by septic shock and % diseased by thromboembolic complications. the deceased subgroup used intubation artificial ventilation in . %, vasoactive drugs in %, and antibiotic therapy in . %. in the surviving subgroup, . % only contracted the nosocomial infection. in the subgroup died . % are of mixed hyperosmolar type + . % hyperglycemic hyperuremic + . % hyperglycemic hypernatremic type. conclusion: hyperosmolar states are an independent a prognosis factor. intubation and ventilation, vasoactive drugs and antibiotic therapy increases considerably in hyperosmolar states. furthermore, it induced serious complications as nosocomial infections and septic shocks that further aggravate the prognosis even within hyperosmolar states. introduction: hyperthermia represents a major life-threatening medical emergency, and is also one of the leading causes of death in young athletes worldwide. its incidence is rare and little understood, but its mortality is on the rise. the objective of this study was to describe the population of patients admitted for exertional hyperthermia in martinique and guadeloupe and to determine the prognostic factors. patients and methods: retrospective and prospective study, including all patients admitted for exertional hyperthermia in both emergency and resuscitation services in martinique and guadeloupe from january to june . results were expressed as mean ± sd or %. results: in years, patients were observed (age- ± , men and women), the main antecedents of which were- hypertension, chronic oh, psychoses, stress hyperthermia. ( %) of the patients had seizures initially. the pre-hospital management was < min. nevertheless, ( %) patients were admitted to icu due to organ failure (neurologic %, hemodynamic %, liver %). the progression was favorable, deaths, including fulminant hepatitis and multi-visceral failure. the average length of stay in intensive care units was days (± ). conclusion: despite considerable preventive measures, stress hyperthermia represents a major problem within the military, soldiers and other athletes, with a mortality rate about % in most published series. the most effective method is immersion in ice water. there is an urgent need to provide the region with a clear preventive policy, including a relief action plan, training for doctors, athletes and other health professionals at risk of hyperthermia. chapoutot anne-gaëlle , leteurtre stéphane , chamouine abdourahim ( ) . the university hospital of lille is a pediatric center including several itecus in its pediatric hematology or gastrology departments, and more recently in its pediatric surgical department. moreover, there are - itecu extra-beds within the - bed pediatric intensive care unit (ivecu). the hospital of mayotte has no pediatric ivecu but a polyvalent one for adults, which receives children when necessary, as well as a bed itecu. the aim of this study was to describe prospectively the pediatric population which was admitted in the itecus of lille and mayotte over a one-year period from june to may . patients and methods: in this twin-center, prospective and observational study, data were collected for each patient admitted during the test period in itecus of both lille and mayotte pediatric hospitalsgeneral information about the patient, characteristics of each stay, severity scores on admission, type of treatments implemented, the report of the stay and patient's evolution. a standard declaration was made with an authorization granted by the local commission on informatics and liberty (french commission informatique et liberté, cil). results: during the course of the study, about children were admitted in each center. the collected data allow to describe and compare both populations in terms of severity of each patient's condition. this study based on a very large cohort has permitted to compare the population of a regional hospital with that of a university hospital and to demonstrate that a health-care provision including a pediatric intensive care unit is needed on mayotte island. introduction: simulation in intensive care is an innovative method for teaching. respiratory settings are responsible for some morbi-mortality of our patients. for this reason we develop a simulator of artificial ventilation (simva) and virtual patients. mathematical model resolved differential equations of chest and lung movements in order to match with a clinical data base. the goal of this study was to evaluate and compare virtual patients respiratory mechanic with the results of different protocols of ventilation from large randomised controlled trial-arma ( ) and express ( ). patients and methods: virtual patients had ards, and were defined by different thoracic and pulmonar compliance, total resistance, lung volumes, pressure-volume relation, and pressure and volume recruitment coefficients. ventilatory protocols were high versus low vt (arma study) and max versus min distension according to pep (express study). each virtual patient was titrated on the simulator with the protocols. respiratory frequency was set around cycles minute and adapted to protocols. respiratory mechanic after titration was recorded and compared to results of the studies. results: results are summarised in the table-the difference between virtual and real patients were not significant. vm l/min . ( . ) . ( . ) . ( . ) . ( . ) . ctp: tharacopulmanar compliance (ml/cmh o) discussion: inspiratory plateau pressure and thoraco-pulmonary compliance were able to change according to pep or vt settings within the same range as the large rct studies. mathematical model of recruitment was adapted to create many different results while pep was titrated according to respiratory mechanics with the express protocol. conclusion: simulation of artificial ventilation with a software can be realistic and might be an interesting pedagogical tool to teach interactively and repetidly ventilatory settings and respiratory mechanics interactions in ards without any risk for the patient in our units. introduction: expiratory flow limitation (efl) has previously been investigated in ards patients on zero peep by using negative expiratory pressure (nep) technique on tidal breath. in ards patients with efl peep improved oxygenation from intrinsic peep homogenization rather than lung recruitment. the nep technique is no longer available. as efl should reflect airway closure it is important to assess it. we described a new technique to assess efl. patients and methods: thirty-nine ards patients ( mild, moderate, severe) were investigated at peep and . they were intubated, mechanically ventilated (evita xl) in volume controlled mode (tidal volume ± ml kg predicted body weight) in the semi-recumbent position. airway pressure and flow measured proximal the endotracheal tube were continuously recorded (biopac ). we measured respiratory mechanics by the occlusion technique at each peep and recruited lung volume between peep and by using low flow inflation method associated with measurement in change in end-expiratory lung volume. for the latter, patient was manually disconnected at the end of baseline tidal inflation downstream pneumotachograph to atmosphere til zero flow, then reconnected at previous settings. efl was assessed offline by superimposing flow-volume loops of disconnected and baseline breath. efl was defined if no change in flow occurred over all or part of the disconnected expiration as compared to the baseline breath and no efl (nfl) if any increase in flow during the expiration was present (fig. ) . the percentage of the tidal volume involved in efl was measured. results: efl was present in patients ( %) over % of the tidal expiration. patients with efl had significant higher body mass index ( ± vs. ± kg m , p < . ) and totalpeep at peep ( ± vs. ± cmh o, p < . ) than nfl patients and tended to be more hypoxemic. at peep efl patients had a significant better compliance ( ± vs. ± ml cm h o, p < . ) with no change in recruited lung volume ( ± vs. ± ml) and tended to be more hypoxemic than nfl patients. mortality at icu discharge was % in efl versus % in nfl (p = . ). conclusion: measurement of efl is feasible without the nep technique. at higher peep ards patients with efl markedly improved compliance of the respiratory system not related to lung recruitment. further studies are required to better understand efl in ards patients and to assess its impact on patient outcome. limiting factor being carbon dioxide accumulation and hypercapnic acidosis. extra corporeal carbon dioxide removal (ecco r) intervenes by maintaining ph and pco within physiological ranges. this combination is called ultra-protective ventilation. we report our experience with ecco r in ards and non ards patients with a focus on feasibility and safety. patients and methods: from june to july all patients who have undergone ecco r in our icu were included consecutively and prospectively. venovenous ecco r was used through a dual lumen venous catheter (femoral or jugular). results: nineteen patients underwent ecco r for a total of sessions. ecco r was implemented through a dual lumen venous catheter (femoral or jugular) with different devices-hemolung respiratory assist system ® (alung) (n = ), ila activve ® (novalung) (n = ) and prismalung ® (prismaflex system) (n = ). sessions were (iqr . - . ) days long. catheter diameters were fr (n = ), fr (n = ), fr (n = ) and fr (n = ). thirteen patients suffered from ards and had non ards indications for ecco r, including ultraprotective ventilation. tidal volume decreased during ecco r from . (iqr . - . ) to . (iqr . - . ) ml kg of predicted body weight (p < . ) while ecco r allowed maintaining of ph and pco within acceptable range (fig. ). driving pressure decreased from (iqr - ) to (iqr - ) cm h o (p < . ). the main adverse effect was thrombocytopenia ( patients). six selected patients had no anticoagulation during ecco r because of high bleeding risk. discussion: ultra-protective ventilation was achieved with a decrease of tidal volumes (vt < ml kg) and positive pressures. few data on ecco r are available in patients at high risk of hemorrhagic complications, we report here a subgroup of patients who underwent efficiently ecco r without anticoagulation. six patients underwent ecco r for non ards indications, of them had no structural damages to the lungs which has never been reported and eccor allowed implementing ultra-protective ventilation with no major adverse effect. we report our experience on ecco r for ards and non ards indications. ultra-protective ventilation (vt < ml kg) was safe and feasible. the impact of general practitioners consultation on ards complicating community acquired pneumonia donval ulysse , tadie introduction: community-acquired pneumonia (cap) is a potentially severe infection that results in numerous general practitioner (gp) visits and hospital admissions each year. cap is also the most frequent single cause of acute respiratory distress syndrome (ards). risk factors for development of ards in the course of cap are not clearly defined although prognostic factors associated with mortality have been extensively studied. gp visits, as an early diagnosis and earlier access to antibiotics prescription could significantly affect the course of cap. the aim of the present study was to evaluate the impact of general practitioners consultation on ards complicating cap admitted to our icu. patients and methods: we retrospectively reviewed the medical records of all patients aged over years admitted between october , and december , , for ards complicating community acquired pneumonia with a pao fio ratio < mmhg after at least h of lung protective mechanical ventilation (mv). ventilatory modalities for ards had been protocolized over the study period as our icu was recruiting patients for two consecutive multicenter trials (acurasys and proseva). consequently, the protective ventilatory strategy used in these two clinical trials was applied to every patient with ards. patients were divided into two groups according to whether or not they visited a gp before icu admission. : patients were admitted for ards complicating cap. patients ( %) had visited a gp before admission in icu (gp +) and did not (gp-). analysis of demographic data, respiratory microbiology patterns, ards severity at admission did not show any differences between the two groups. sofa score at admission was significantly higher in gp-compared to gp + patients ( . ( - ) vs. . ( - ) respectively + p = . ) although respiratory sofa scores were not different ( ( - ) vs. ( - ) respectively + p = . ). ( %) gp-( %) and ( %) gp + patients presented septic shock at icu admission (p = . ). multivariate analysis found that gp consultation ( . [ . - . ] + p = . ) with antibiotics prescription ( . [ . - . ] + p = . ) were associated with decreased mortality at day ( fig. ) . in patients admitted to our icu for ards complicating community acquired pneumonia, gp visits prior to icu admission was associated with a better outcome. the beneficial effect may be due to earlier antibiotic prescription which could significantly lowered severe infection and septic shock. introduction: optimal peep level during ards remains controversial because of its beneficial and adverse effects. the optimal level of recruitment and its effect on oxygenation are not well defined and no technique is currently validated. the aim of our study was to evaluate the correlation between the recruited pulmonary volume estimated by a new technique (crf inview ® ) and the evolution of pao as well as the respiratory and hemodynamic tolerance of the application of an increasing levels of peep . patients and methods: a prospective, monocentric study that will last years (january -january ), taking place in the intensive care unit at the military teaching hospital of tunis and including patients if they met standard criteria for ards (berlin criteria). the main criterion for judgment was the correlation between the recruited pulmonary volume estimated by a new technique (crf inview ® ) and the evolution of the pao after application of three increasing levels of peep ( - - ). the other secondary criteria were the respiratory and hemodynamic tolerance of the application of increasing levels of peep measured by the picco ® technique. aimed to investigate the concordance between the onset of three vae tiers and valrti, and their impact on outcomes. we performed a retrospective analysis of prospectively collected data from patients requiring mechanical ventilation for more than days in a -bed mixed icu of a tertiary university teaching hospital, between january and december , . vat and vap episodes were assessed by prospective surveillance of nosocomial infections, according to the american thoracic society criteria. vae were identified retrospectively, according to current cdc definitions. the agreement between vac, ivac, pvap and valrti was assessed by k statistic. the impact of vae and valrti on duration of mechanical ventilation, icu and hospital length of stay and mortality was also assessed for the first episode of vat and vap. results: we included patients ( ventilator days). vap ( . per ventilator-days), vat ( . per ventilator-days) and vae ( . per ventilator-days) were diagnosed. there was no agreement between vat and vae and the agreement was poor between vap and vac (k = . , % ci . - . ), vap and ivac (k = . , % ci . - . ) or vap and pvap (k = . , % ci . - . ). patients who developed vat, vap or vae had significantly longer duration of mechanical ventilation, icu and hospital length of stay, compared to patients who did not, with similar mortality rates. conclusion: vae are not relevant for vat diagnosis and have low agreement with vap, despite their negative impact on ventilation duration, icu and hospital length of stay ( fig. ) . the introduction: post-operative pneumonia (pop) is a frequent and severe complication of major lung resection surgery. in , we changed our surgical antibioprophylaxis protocol from cefamandole to amoxicillin-clavulanate and observed a significant decrease of pop incidence and mortality. in , we additionally implemented in the respiratory intensive care unit (ricu) an antimicrobial stewardship program based on a local antimicrobial guideline and a weekly multidisciplinary review of all antibiotic therapies by ricu physicians, infectious diseases specialists and microbiologists. our objectives were to describe our current epidemiology of severe pop and to assess the quality of antibiotic prescriptions. patients and methods: all patients with severe pop occurring within days after lung resection between january and december were included. we collected data on clinical presentation, results of microbiological investigations, antibiotic regimen and outcomes. the quality of antibiotic use was assessed using indicators previously validated in the literature. results: over patients who underwent major lung resection in our center, matched criteria for severe pop and were included. most were males (n = , %). the median age was years (minimum- + maximum- ). most patients had chronic obstructive pulmonary disease (n = , %) and ( %) a history of non-pulmonary cancer. the resection consisted in lobectomy in % (n = ). the median length of stay in ricu was days ( + ), and -day mortality was % (n = ). respiratory microbiological samples were obtained in all patients, in most cases invasively per bronchoscopy ( %). microorganisms were cultured at a significant level in ( %) patients. predominant species were enterobacteriacae ( %), haemophilus influenzae ( %), staphylococcus aureus ( %) and pseudomonas aeruginosa ( %). microorganisms were sensitive to third generation cephalosporins in ( %) and to piperacillin-tazobactam in ( %). in patients treated empirically, antibiotics were prescribed according to the guideline in % ( ). in documented pop, empiric antibiotics were active against documented micro-organisms in ( %), and were correctly changed to pathogen-directed therapy in ( %). the median duration of antibiotics was of days ( + ). conclusion: ten years after implementation of amoxicillin-clavulanate as surgical antibioprophylaxis, the proportion of enterobacteriacae increased. the -day postoperative mortality rate remained below %. we report high adherence to the guideline for the choice of empirical therapy and treatment duration. the rate of de-escalation to pathogen-directed therapy could however be improved considering the high rate of bacteriologically-documented pop. resistance of pa has reduced between both periods from % to % (p < . ) for ceftazidim, from % to % (p < . ) for cirpofloxacin and from % to % (p < . ) for imipenem. nevertheless, among the cases, the p period did not change the risk of developing an infection (rr = . , ci % . - . ), a vap (rr = . , ci % . - . ), a septicemia (rr = , ci % . - . ) or the mortality rates (rr = . , ci % . - . ). conclusion: colonization and infection with pa are risk factors of increased mortality rates and alos in icu. an antibiotic stewardship program allows to reduce the incidence of patients having a positive sample with pa, and the antibiotic resistance of pa strains, without reducing the infection rate of these patients. impact of a local care protocol on the duration of antibiotic therapy in community-acquired peritonitis: years of experience introduction: the use of antibiotics is a major public health, economic and ecological challenge. in , a french national warning plan was created to manage the use of antibiotics. it advocates monitoring of the prescription of antibiotics and the implementation of measures to assess professional practices. the great majority of guidelines concerning the duration of antibiotic therapy in community-acquired peritonitis are based on studies with low level of evidence. the objective of this study is to evaluate the implementation of a standardized operational report (sor) with a local antibiotic protocol in the management of community-acquired peritonitis at our institution. patients and methods: this is a monocentric, prospective cohort study-before and after the establishment of the sor. the primary endpoint is duration of antibiotic therapy. secondary endpoints are length of hospitalization, infectious complications, mortality, and changes in local bacterial ecology. we have also evaluated retrospectively these different criteria on cohort was constituted since . results: a total of patients were enrolled from january to june and patients from may to may . the duration of antibiotic therapy was decreased by to days in localized peritonitis (p < . ) and to days in generalized peritonitis (p < . ) (figure) . however, the compliance to the protocol was only %, which leads to an increase in the duration of antibiotic therapy and hospital stay when not used (p < . ). the hospital stay decreased from to days in the localized peritonitis (p < . ). amoxicillin clavulanic acid (amc) is the most used antibiotic with an efficiency of %. there was no impact on morbidity and mortality when amc was inadequate. the bacterial ecology was not modified, the rate of extended-spectrum beta-lactamase (esbl) producing enterobacteria (esble) was %. the use of a standardized antibiotic protocol reduced antibiotic therapy duration and hospital stay, particularly in localized peritonitis despite incomplete compliance to the protocol. to achieve full compliance, we need to continue the training of different physicians and continue the spread of the protocol. introduction: bacterial meningitis is an important public health problem because of its frequency and severity. they remain a major cause of mortality and morbidity in developing countries. the aim of our work is to establish the epidemiological characteristics and the prognostic factors . patients and methods: we did a retrospective descriptive and analytical study and we included all the patients admitted for severe meningitis for year in the medical intensive care unit of the university teaching hospital ibn rushd at casablanca-morocco. results: patients were included. the incidence of severe meningtis was . %, the mean age was years old and the sex ratio h f was , . , % were pneumococcal meningitis and % were tuberculosis in univariate analysis, factors influencing mortality significantly-the male sex patients with pulmonary tuberculosis as an antecedent.• a low glasgow score at admission. the presence of a neurological deficit arterial ph, mean (sd) arterial lactate, mean (sd) kidney disease-improving global outcomes chronic kidney disease guideline development work group members. evaluation and management of chronic kidney disease-synopsis of the kidney disease-improving global outcomes clinical practice guideline dramatic increase in venous thromboembolism in children's hospitals in the united states from antithrombotic therapy in neonates and children acute childhood arterial ischemic and hemorrhagic stroke in the emergency department childhood hemorrhagic stroke-an important but understudied problem emergency management of deeply comatose children with acute rupture of a cerebral arteriovenous malformation goulmane mourad -m.goulmane@hotmail.com annals of intensive care we recorded episodes of nosocomial infections-pneumonia (n = , . %), bacteremia (n = , . %), catheter related infections cri (n = , . %) and urinary infections (n = , . %). pathogens isolated were largely dominated by non-fermentent gram-negative bacilli (n = , . %)-acinetobacter baumanii (n = , . %) with % resistance to imipenem and tygecycline, pseudomonas aeruginosa (n = , . %) with . % resistance to ceftazidim and stenotrophomonas maltophila (n = ). other gram-negative bacilli were enterobacteries (n = ), which were wide-spectrum betalactamase secreting (n = ) and carbapenemase (n = ). gram-positive cocci were the second highest (n = , . %)-coagulase negative staphylococcus (n = ) which were resistant to methicilline ( %), enterococcus (n = ) which were resistant to vancomycin (n = , . %), staphylococcus aureus sensitive to methicilline (n = ) and streptococcus (n = ). candida was incriminated in cases of cri we report here that neonates had a reduction in hla-dr expression after cpb, and those with prolonged decreased hla-dr in the early postoperative period (day ) could represent a subpopulation at greatly increased risk of later ni. if confirmed in a larger cohort of patients, our findings could indicate that hla-dr may be a useful biomarker of immunosuppression after cpb in neonates. non-traumatic hemorrhagic stroke (nths) in comatose children: epidemiological features and clinical presentation conclusion: compared to normobaric ltot the fio is lower during niv with the same o flow. compensation for intentional and nonintentional leaks and so an increase of air flow despite a constant o input might explain this. in intermediate care the use of hv for niv may be interesting alternative in which case the clinician must keep in mind that the fio decreases compared to standard oxygen therapy. concerning home usage we hypothesize that this partial removal of o treatment could contribute to the poor results of niv in chronic copd. introduction: in february , we opened a beds-post icu rehabilitation center (service de rééducation post réanimation, «srpr»), dedicated to weaning from mechanical ventilation and global post icu rehabilitation. objectives-description of the characteristics and main outcomes of the patients admitted over the first year of activity. patients and methods: retrospective analysis of data extracted from the medical files. results: patients were admitted times in the unit over its st year, from different icus (median duration of stay in the icu . days (iqr - )). % were ventilated ( % with niv). % had a tracheostomy. % had icu acquired weakness + % were able to walk. an underlying chronic respiratory disease was present in % of cases. % were obese. difficult weaning was found to have one or several respiratory components in % of cases (including post surgery diaphragmatic paralysis), cardiac in %, neurologic in %. significant complications occured in % of cases. median duration of stay was . ( - . ) days. ten patients died in the unit, patients were re-transferred in the icu, where of them died. over half of the patients were discharged at home, in a rehabilitation unit (ssr) or in a hospital ward awaiting a rehabilitation bed. the remaining %, that still needed some form of medical or surgical care were discharged in the ward (fig ) . in intention to treat, successful weaning from invasive ventilation was obtained in % of patients. of the patients discharged alive from the unit after completing the rehabilitation program (n = ), % were completely weaned from mechanical ventilation, % were discharged with niv or cpap + patients ( %) were considered not weanable from invasive ventilation + decanulation of tracheostomy was obtained in % of cases + % of the patients could walk. conclusion: srprs offer a new concept of care for difficult to wean patients, with promising results. introduction: scarce data about patients with prolonged weaning from the mechanical ventilation are available in the literature. patients without successful weaning days after their first weaning attempt were classified in the group of the weaning according new definition (wind) classification ( ) . we here describe specific data concerning weaning and hospital evolution of group patients included in this prospective cohort. among the patients included in the wind study, were classified in the group . additional data concerning comorbidities, cause of weaning failure and hospital evolution were collected for ( %) of these patients. results: these patients had median [interquartile range] duration of invasive mechanical ventilation of [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days and [ ] [ ] [ ] separation attempts. etiology of icu hospitalization was medical in ( %). they had a copd in ( %), hearth disease in ( %) and immusoppression in ( %). we noticed a mean saps ii of ± , a mean sofa d of ± and d of ± . tracheostomy for weaning was performing in ( %). at the end of their follow-up, ( %) were still alive- ( %) were still tracheostomized, still intubated and ventilated, ( %) treated with vni and ( %) were extubated (or decannulated) and breathed without assistance. among the patients still tracheostomized at the end of the follow-up, ( %) were still ventilated (permanently for of them, and partially for ) and ( %) had spontaneous breathing through their tracheostomy. these patients had a total icu length of stay of days. the destination at discharge from the icu is known for only of the survivors- ( %) in medical ward, ( %) in intermediate care units, ( %) in sub acute care, ( %) in icu and in surgical ward. conclusion: a third of the patients of the wind study classified in group and with available additional data died in hospital in months following intubation. at the end of the follow-up, % had spontaneous breathing without assistance, and % were still tracheostomized. among these tracheostomized patients, one third still required mechanical ventilation. ( )-béduneau, g., pham, t. and co ( ) . epidemiology of weaning outcome according to a new definition. the wind study. ajrccm, ( ) , - . introduction: copd patients have often polyglobulia because of associated hypoxemia especially in patients at the stage of chronic respiratory failure. we recently reported that anemia was present in % of patients with severe aecopd admitted to icu without impact on short-term prognosis. the aim of the present study was to assess the long-term impact of haemoglobin (hb) levels on outcomes of aecopd patients. patients and methods: in a prospectively collected database including consecutive patients admitted between and for aecopd in our icu. long-term status of patients following the first icu admission (surviving or deceased) has been verified by consulting the civil status registers. anemia was defined according to who criteria-hb < g dl in males + hb < g dl in females. long-term survival was assessed by kaplan-meier curve. results: the cohort included patients (median age , median ph . , . % males, niv as first ventilator mode in . %). anemia was observed in of the patients ( . %) with median haemoglobin levels at . and . g dl, in patients with and without anemia, respectively. anemia was associated with significantly lower years survival (log rank p = . ) (fig. ). the final model included age, saps ii score, comorbidities, home oxygen therapy, initial ventilatory mode, niv failure and haemoglobin levels. multivariate analysis identified age (or . per year + ic % . - . + p = . ), home oxygen therapy prior to exacerbation (or . + ic % . - . + p = . ), intubation at icu admission (or . + ic % . - . + p < . ), niv failure (or . + ic % . - . + p < . ), and haemoglobin (or . per decrease of g dl + ic % . - . + p = . ) as independently associated factors with years mortality . we conducted a prospective observational study including all patients who visited the sis during the last months. the collection of the usual anonymous demographic, medical and toxicological data was performed by the care-givers and social workers in charge of the drug users. data were declarative and no analytical confirmation was available except for the patients admitted in the icu. results discussion during months, drug users [f m sex ratio . + median age . years ( - ) + patients without resources ( %), without medical insurance ( %), unstable housing homelessness ( %)] visited the sis for drug injection or inhalation, representing , drug use including , inhalations and , injections by drug users day. drug users had no addictology ( %) or sociomedical ( %) follow-up. they were infected by hepatitis virus c ( %) and or hiv ( %). they declared to continue injecting in the public space ( %), sharing material ( %), and needles syringes ( %). the injected inhaled drugs in the sis were skenan ® (morphine, . %), crack ( % including injections), methadone ( . %), buprenorphine ( . %), heroine ( . %), and cocaine ( . %). these drugs were self-administered by polydrug users declaring concomitantly consuming crack ( . %), illicit morphine ( . %), cocaine ( . %), ethanol ( . %), cannabis ( . %), heroin ( . %), illicit methadone ( . %), benzodiazepines ( . %) and illicit buprenorphine ( . %). forty-five patients required a paramedical intervention in the sis resulting in calls to the emergency department and hospital admissions including transfers to the icu in relation to opioid overdose. no cardiac arrest and no death occurred. conclusion: sis visit for recreational drug self-administration rapidly becomes popular among drug users. illicit morphine (skenan ® ) glycemia (mmol/l) . ( - ) . ( - )ketones in the effluent liquid (g/l) . ( . - . ) ( - ) patients and methods: physiological tracings were recorded from the standard monitoring system (intelliview mp philips), using a dedicated network and extraction software (synapse v , ltsi inserm u ) that enables photoplethysmographic recordings from oximetry monitoring at a native resolution of hz. raw data were subsequently stored on a dedicated local server, before anonymization and analysis. all consecutive patients were recorded for a -hours period during the -hours following icu admission. all measurements were recorded with the patient laying supine, with a ° bed head angulation. physiological recordings were associated with metadata collection by a dedicated research assistant.hrv parameters defined in a previous study were derived using kubios hrv premium ( introduction: preventing post liver transplantation (lt) hepatic artery and portal vein thrombosis is challenging and includes enoxaparin administration. enoxaparin pharmacokinetics (pk) has not been investigated in children following lt. between-subject variability and critical illness may alter pk, leading to the risk of subtherapeutic exposure. patients and methods: clinical, biological and kinetic data were retrospectively collected in a single pediatric intensive care unit center from january to july . we described an enoxaparin pk model in children the first week following the lt. anti-xa activity timecourses were analyzed using a non linear mixed effects approach with monolix version r. results: anti-xa activity time-courses were well described by a one-compartment open model with first order absorption and elimination. body weight prior the surgery (bwpreop) and the related postoperative variation (bw(t)) were the main covariates explaining cl and v between subject variabilities. parameter estimates were cli = cltyp*(bwpreop ) + vi = vtyp*(bw(t) ) + where typical clearance (cltyp) and typical volume of distribution (vtyp) were . l h − and . l, respectively. standard dosing regimens of iu kg h were insufficient to reach the target range of anti-xa activity of . to . iu ml. specifically, children ( %) did never attain the target range during the whole period of treatment and all children were at least once under dosed. according to the final results, we simulated individualized dosing regimens within h following the first administration. more than iu kg h are suggested to reach the target range of anti-xa activity of . to . iu ml from the first day. standard enoxaparin dosing regimens is not appropriate to reach the target in pediatric liver transplantation patients. enoxaparin pk modeling should help the physician to achieve the target range from the initial dose and during the maintenance doses. higher dosing regimens, especially in youngest children are suggested to achieve the prophylactic target range. pharmacokinetic analysis of unfractionated heparin in critically ill children during extracorporeal membrane oxygenation: do we achieve the target? introduction: preventing thrombosis in children under extracorporeal membrane oxygenation (ecmo) requiring unfractionated heparin administration. unfractionated heparin pharmacokinetics (pk) has not been well investigated in children under ecmo. we described the unfractionated heparin dosing regimens and resulting anti-xa activities in children with ecmo. patients and methods: this is a single center retrospective study from march to september . were included children (< years old age) who were under ecmo for refractory hemodynamic failure related to (i) myocarditis or (ii) septic shock. anti-xa activity timecourses were analyzed using a non linear mixed effects approach with monolix version r. results: a total of children were included (septic shock, n = + myocarditis + n = with a median age of months ( - ), a median weight of . kg ( . - ) and median admission pelod- score of ( - ). bleeding occurred in children and thrombosis in . an initial bolus of unfractionated heparin ranging from to iu kg was infused and then continued by continuous perfusion with an initial dosing ranging from iu kg h to iu kg h. a total of anti-xa activity measurements were performed between h empirically antibiotics for these patients with severe infection may be recommended. introduction: prognosis of allogeneic hematopoietic stem cell transplant (hsct) recipients admitted to icu has improved with advances in hsct procedures and critical care management, but also with evolution in icu triage policy. our aim was to describe the outcome of hsct recipients admitted to icu according to a wide admission policy. patients and methods: retrospective multicenter study including all consecutive allogeneic hematopoietic stem cell transplant (hsct) recipients admitted to saint-antoine hospital medical icu, paris, france from to january to april . admissions were identified through a systematic review of icu database using icd- codes z and t . data were extracted from medical charts. qualitative and quantitative values are expressed as number and percentage, and median and interquartile range, respectively. comparisons between groups were performed using fisher's exact test and mann-whitney test for qualitative and quantitative variables, respectively. a p-value < . was considered to be significant. results: one hundred seventeen patients- men ( . %), median age [ - ] years-were included in the study. underlying hematological malignancies were: acute myeloid leukemia (n = , . %), myelodysplastic/myeloproliferative neoplasms (n = , . %), acute lymphoid leukemia (n = , . %), lymphoma (n = , . %), other ( . %). complete remission was achieved before hsct in ( %) patients. forty-nine ( . %) patients underwent myeloablative conditioning regimen and ( . %) received haploidentical grafts. twenty-eight ( . %) patients experienced disease relapse after hsct and ( %) graft versus host disease prior icu admission. median saps ii was and sofa score at day one [ - ]. the icu, hospital and -day mortality rates were respectively . , . and . %. in univariate analysis, factors associated with -day mortality were: saps ii (p = . ), invasive mechanical ventilation (p < . ), vasopressors (p = . ) and renal replacement therapy (p = . ). mechanical ventilation was the only independent factor of -day mortality (or . - . ], p < . ) with mortality rate reaching . % and even . % among patients with uncontrolled hematological disease. conclusion: prognosis of unselected hsct recipients admitted to icu remains poor, particurlaly among those receiving mechanical ventilation, and even more if hematological disease is not controlled. these results suggest that the implementation of an icu triage policy determined both by intensivits and hematologists would be helpful to identify good candidates for icu admission. introduction: acute respiratory failure (arf) is a common event in patients with primary malignant brain tumors (pmbt). even if many factors (corticosteroid therapy, swallowing disorders) suggest a specific etiologic spectrum, few data are available regarding its precipitating factors. our first aim was to compare the causes of arf between patients with pmbt and those with other type solid tumors. our second aim was to identify, among pmbt, the factors influencing survival in icu. patients and methods: bicentric case-control study from march to may . patients with pmbt (cases, primary central nervous system lymphoma included) admitted for arf were compared to patients with other kind of solid tumors (controls). the reason for admission "arf" as well as the causes of arf was determined by three experienced respiratory physicians and were required for inclusion: a respiratory rate > cycles/min and a pao /fio < for patients in spontaneous breathing and only a pao /fio < for patients under mechanical ventilation. in both groups were excluded patients with metastatic solid tumors, benign tumors or tumors with more than years of complete remission, recent post-operative patients, and patients with other immunodeficiency. results: a total of cases and controls were included. main patients' characteristics are reported in the table . acute infectious pneumonia was the leading cause of arf in both groups but was more frequent among cases ( vs. %, p < . ). cardiogenic pulmonary edema and exacerbation of chronic respiratory diseases were more frequents in controls ( vs. %, p < . ). pulmonary embolism was similar between the two groups ( vs. %, p = . ). among acute infectious pneumonia, pneumocystis pneumonia (pcp) and aspiration pneumonia were more frequent in cases ( vs. %, p < . and vs. %, p < . respectively). in multivariate analysis cancer progression (or- . %ic [ . - . ], p = . ), need for intubation (or- . %ic [ . - . ], p = . ) and respiratory rate (or- . % ci [ . - . ], p = . ) independently predicted icu mortality of pmbt patients. conclusion: in pmbt patients, the causes of arf differ significantly from other cancer patients. up to % of the admissions was related to preventable causes (pulmonary embolism, pcp) and a curable cause was identified in the majority of cases. our results suggest that pmbt alone is not a relevant criterion for icu recusal. introduction: drug intoxication is a common problem encountered in emergency departments. poisoning remains a major cause of hospitalization for young people, and that of the elderly is constantly increasing. objectives . determine the epidemiological characteristics of addicted patients . know the clinical manifestations of poisoning. patients and methods: a retrospective study of cases of acute poisoning recorded at the university hospital center chuoran between january and december was carried out. seizure on data processing by epi-info version . results: cases of acute poisoning, with an age ranging from to years. female patients predominated with %. people between the ages of and are the people most affected by poisoning. the nature of poisoning is varied. in this series, analgesics were found to be the leading cause of acute intoxication, with cases, % followed by psychotropic drugs ( %), benzodiazepines ( %), neuroleptics ( %), antiepileptics%) and antihistamines ( %). the majority of acute intoxications were managed within an average time of . ± . h with an interval between . and h. in % of cases the poisoning was asymptomatic, there were digestive manifestations in % of patients, % neurological, % cardiovascular and % respiratory. we deplore death in this series secondary to many drug poisoning. conclusion: acute drug poisoning is a common reason for admission to the emergency department of oran university hospital. the large number of drug families offered for sale, as well as the heterogeneity introduction: selective serotonin reuptake inhibitors (ssris) have been considered for their low toxicity comparatively to antidepressant agents. the present study aims to describe clinical features and prognosis of poisoning ssris. patients and methods: a retrospective study of patients admitted to our -bed teaching icu for acute ssris poisoning over a period of years from january to december . ssris poisoning was retained on a history of over dose ingestion, clinical signs and positive urine samples for ssris. results: thirty seven patients were collected, the middle age was ± years with a female predominance ( . %). a psychiatric history with depressive syndrome was noted in . % and a history of suicide in . %. paroxetine was the main invoked drug (n = ), followed by sertaline (n = ), then fluoxetine (n = ), venlafaxine (n = ) citalopram (n = ). the mean supposed ingestion dose was . mg. intoxication was pure in cases and associated with other drugs in cases-benzodiazepines (n = ), klippal (n = ), amisulpride (n = ), non-steroidal anti-inflammatory drug (n = ), prazin (n = ) and promethazine (n = ). neurological examination found drowsiness and mydriasis in % of cases (n = ), coma in . % (n = ), agitation (n = ), tremor (n = ), hyperreflexia (n = ), hypersudation (n = ), fever (n = ) and diarrhea in one patient. the qt was lengthened in five cases. treatment was symptomatic. five patients ( . %) required mechanical ventilation with average of ventilation duration of . h. all patients discharged alive the icu. conclusion: ssris poisoning is mainly manifested by serotonergic syndrome. evolution is favorable in the majority of cases. mechanical ventilation could be required. hemodynamic profile of shocks induced by dihydropyridine calcium channel blocker poisoning khzouri takoua introduction: acute calcium channel blockers (ccb) poisoning remains infrequent despite their increasing use. in our country, dihydropiridines are the most prescribed ones. very few works have studied the hemodynamic profile of acute dihydropyridines poisoning either by invasive means (right cardiac catheterization, transpulmonary thermodilution) or non-invasive (cardiac ultrasound). in this perspective, we carried out this study whose main objective was to illustrate the different hemodynamic profiles of shocks induced by dihydropyridine ccb poisoning. patients and methods: it was an observational retrospective study spread over months from st january to th december in a teaching toxicological icu, including all patients admitted for acute dihydropyridine ccb poisoning, who presented a shock and underwent right hemodynamic exploration.results: during the study period, ccb poisoning accounted for . % (n = ) of all the acute poisoinings requiring hospitalization in our intensive care unit. among them, had taken dihydropyridine which represents . %. four women aged of [ , ] were eligible. all the exposures were single-drug. the dihydropyridines involved were amlodipine in cases with a median value of supposed ingested dose (sid) of . mg and nicardipine in the other two ones, the median sid was mg. the delay of consultation was of . ± h after ingestion. gastrointestinal decontamination was performed in one patient with activated charcoal. the patients developed a shock within h, treated by initial vascular filling on average ml of crystalloids, noradrenaline alone in cases and with a combination of dobutamine in one patient. other adjuvant treatments (high dose insulin, calcium salts) have been used in all patients. their hemodynamic profile evaluation by right-handed catheterization swan-ganz was in favour of vasoplegia in cases with median values of systemic vascular resistances (svr) of dynes.s.cm- , of cardiac output (co) of (l min), and of the arteriovenous oxygen difference of . . the fourth patient's shock had mixed nature with svr of dynes.s.cm- and co of . (l min). all patients were discharged from the icu with a mean length of stay of days. conclusion: the dihydropyridine calcium channel blockers poisoning exposes to the shock risk due to several mechanisms. the clinician must be warned to look for signs of severity and understand its mechanisms by using the hemodynamic study in order to improve its management. goulmane mourad , alachaher djamel , djebli houria introduction: in daily practice, admission to the intensive care unit (icu) usually does not raise any major ethical problems. difficulties arise mainly in acute situations requiring intensive care that have not been anticipated and therefore, not adequately prepared and discussed. we hypothesized that non-admission of a patient to the icu must occur in the following circumstances-( ) with the patient's agreement, expressed either directly or through advance directives (ad), or as relayed by a surrogate or the family + ( ) according to a collegial decision-making process (if the patient is decisionally incapacitated) + and ( ) after seeking the opinion of an external consultant. the decision-making process must be documented in the patient's medical file. patients and methods: prospective, observational study in two hospitals (one large university hospital, one regional non-acamedic hospital) over a period of months. inclusion criteria were-patients aged ≥ years presenting with failure of at least organ that was directly life-threatening and requiring life-sustaining therapies. complete data collection was performed for each patient. results: a total of patients were included ( % from the emergency department and % from medical wards). the decision not to admit the patient to the icu was taken-( ) during night duty for patients ( %) + ( ) by a senior physician in %, and ( ) after clinical examination in ( %). the main reasons justifying the decision not to admit to the icu were-( ) metastatic cancer in patients ( %) + ( ) total loss of autonomy in ( %) + ( ) severe cognitive impairment in ( %) + ( ) premorbid state in ( %) + ( ) chronic organ failure for ( %) + and ( ) presence of ad (written or oral) specifying that the patient did not wish to be admitted to the icu in ( %). this study raises several points concerning the decision-making process for patients requiring intensive care. first, collegiality is observed in almost all situations of non-admission ( %). second, an outside consultant was contacted in around % of cases. third, % of patients had ad. fourth, the family or entourage were consulted in less than % of cases and finally, in around % of cases, the decision-making process was documented. conclusion: this study shows that in emergency situations, it is more difficult to take adequately structured decisions regarding icu admission than, for example, decisions regarding limitation or withdrawal of treatment in the icu. introduction: as known, tracheostomy is performed to improve quality of life (qol) in patients requiring prolonged mechanical ventilation. it is indicated to facilitate care of critically ill patients, in order to minimize risks of oro-tracheal intubation, and enhance recovery, allowing early discharge from icu with home ventilation. we aimed by this study to evaluate long-term survival and qol in tunisian patients discharged from the icu with tracheostomy, as well as related burden assumed by their relatives. patients and methods: patients who were admitted to the icu between and were eligible for inclusion in this retrospective cohort if they had a tracheostomy during their icu stay, and were discharged at home with a tracheostomy canula. for survivors, we used the short form health survey (sf ) to assess their qol at home. we estimated the degree of autonomy using the adl scale. to assess burden assumed by caregivers (family members most of the time) we used the short version of zarit burden interview. exclusion criteria were refusal of the interview or unavailability on the phone call. results: fourteen patients were discharged at home with a tracheostomy canula. only twelve responded to the phone call. four patients died month later. amoung the survivors, the removal of the tracheostomy canula was successful in patients after a mean duration of days. main findings are summarized in table . conclusion: tracheostomy shows good acceptance and acceptable qol. it allowed shorter length of stay in the icu and long-term survival after discharge from the icu, and should be encouraged for tunisian patients. in contrast, the qol of patients' relatives was more affected, with significant burden and work load. introduction: intensive care survivors present often some psychological disorders linked with experience memory loss or nightmares. the use of patient diaries has been developed and implemented by clinical staff to improve the quality of life after intensive care. patients received their diaries at icu discharge. this study was conducted in order to understand the potential benefits for patients the diary on prevalence anxiety, depression and post traumatic disorders during recovery. patients and methods: a structured interview study was administered to adult critical illness survivors who received ≥ h of mechanical ventilation in a medical and surgical intensive care unit. after months, this patients answered at two questionnaire-hospital anxiety and depression scale (had) and a screening instrument for ptsd (qspt). results: from the survivors at months, patients answered the questionnaires. we have two groups- patients had a diary and patients no diary. but these group are so low currently to compare introduction: in ards patients under ecmo common ventilator strategy aims at resting the lung by lowering tidal volume (vt) in the - ml kg predicted body weight range found in the literature analysis. we tested on the bench the not previously explored hypothesis that vt was not delivered in the % accuracy by most of icu ventilators in this low range. patients and methods: pneumatic test lung set at ml/cmh o compliance and cm h o/l/s resistance was attached to any of icu ventilators (v (drager), carescape r (ge healthcare), servo u (maquet), pb (covidien) and g (hamilton)) equipped with heated humidifier (fisher-paykel mr ) set off and adult ventilator circuit (rt evaqua fisher paykel). each icu ventilator was set in btps condition, at peep cm h o and fio . . airway pressure and airflow (hans-rudolph pneumotachograph) were measured (biopac m ) proximal to the lung model. for each ventilator a series of vt ranging from to ml was delivered for breaths each, at then at breaths/min respiratory rate (rr). the relationship of vt measured to vt set was assessed by linear regression over the icu ventilators for each circuit-rr combination. in each model, the change from the mean effect was assessed for each ventilator. for each model we obtained the mean effect of the ventilators then we compared the effect of each ventilator to the mean effect. results: for each combination of f and circuit, the mean slope was significantly lower than indicating that, on average, the set vt was under delivered (table) . there were differences in change in slope from the mean across the ventilators with interaction between ventilators and combinations. as an example, for the adult circuit f , carestation, pb and servo u performed better than g and v . across the combinations, v had consistent negative (greater underestimation than average) slopes and servo u consistent positive (lower underestimation than average) slopes whilst the slope sign in the three others changed direction. biomarkers. yet, hla-dr expression on alveolar monocytes was lower in ards than in controls, consistent with sepsis-induced immunosuppression at the alveolar level. functional differences observed between ards and controls suggested a tolerogenic profile of ards monocytes. introduction: despite their recommendation in the prevention of ventilator-associated pneumonia, oral care is not still clearly standardized. it generally includes a time for oropharyngeal and tracheal suctions which can induce a cough reflex in non-paralyzed patients leading to the mobilization of the endotracheal tube and a consecutively increased risk of tracheal microaspirations. during the oral care procedure, drainage of subglottic secretions at particular times before oro-tracheal suctions is expected to reduce microaspiration. the aim of this study is to assess whether this "optimized" oral care including subglottic drainage can reduce microaspirations. this is an open prospective study, including icu ventilated patients. two procedures have been compared in two randomized cross-over consecutive periods of one day each ( oral cares a day)-on day, they received routine oral care (oral care (o) then tracheal suction (t)) and on the other day they received optimized oral care (subglottic suction (sg ) then o then sg then t). the amylase enzymatic activity has been measured in o, t, sg and sg suctions as a surrogate for the oropharyngeal content. if present in t suctions, it defines microaspiration. since the amylase o content is not similar from a patient to another, the primary outcome was the median amylaset o ratio after routine versus optimized oral care. results: after informed consent, patients were included. were analyzed due to incomplete follow-up in patients. patients (sapsii ± ) were ventilated since . ± . days for a majority of respiratory indications. at day , and patients received routine oral or optimized oral car respectively without significant baseline difference. a trend in the reduction (− %) of amylase t o median ratio was observed after optimized versus routine oral care ( . % [ . - vs. . % [ . - ], p = . . conclusion: despite protection of trachea by the cuff of the endotracheal tube, amylase has been found in tracheal suctions (which represents the last step of oral care). in this pilot study with a limited sample of patients, a trend in the reduction of microaspirations was observed when subglottic suctions were interleaved between oral and tracheal suctions. an increased sample power could show more significant results, but we cannot eliminate that this weak effect could also be due to the inability of subglottic suctions to prevent microaspiration of the oral content. the study has been founded by teleflex. introduction: although necessary, mechanical ventilation can lead to ventilator-induced lung injury (vili) even when using protective ventilation strategies that combine low tidal volume (vt)( ml kg predicted body weight) and plateau pressure (pplat) <= cmh . lower positive pressures and tidal volumes could enhance lung protection + the hla-dr and pd-l expressions were higher on alveolar than on blood monocytes in both ards patients and controls (figure) . yet, hla-dr expression on alveolar monocytes was higher in controls compared to ards patients (p = . ). circulating monocytes had a higher phagocytic activity than alveolar monocytes (p < . ), but no significant difference was observed between ards patients and controls. an lps challenge increased the phagocytic activity of monocytes in controls (p = . ) but not in ards monocytes (p = . ). tnf-α intracellular synthesis was increased after lps exposure in circulating and alveolar monocytes of controls (p < . ) but only tended to do so in ards (p = . ). conclusion: differences in the phenotype of alveolar and circulating monocytes were observed in ards but also in controls, suggesting a physiological lung blood gradient in the expression of these results: until , ten patients were included and analyzed for the study. there was a significant difference between the volumes recruited at the three peep levels (p = . ). the recruitment evaluated was not correlated with pao . there is a significant decrease in cardiac index and pam caused by the increase in peep. conclusion: preliminary results from our study suggest that the estimated recruited lung volume estimated by crf inview ® technology appears to be poorly correlated with measured pao . the hemodynamic repercussions observed should also be considered in order to propose an optimal strategy for the optimal adjustment of peep. were compliant with the re-evaluation. ( %) patients received carbapenems according to the recommendations. a compliant prescription had no impact on hospital or icu length of stay and no impact on duration of mechanical ventilation but seemed associated with increase mortality (p = . ). discussion: the high rate of compliant prescriptions can be explained by the broad indications of carbapenems in the icu, especially in patients with septic shock. the increase mortality of patients with a compliant prescription is probably due to the severity of the infections. in order to achieve % compliance, we could suggested regularly updating the knowledge of carbapenems prescriptions, collaborating with bacteriology and infectiology teams, and establishing a computerized or paper prescription with feedback control. conclusion: the prescription of carbapenems appears most often in accordance with the recommendations in this icu. however, there is a need for improvement. introduction: bacterial infections are frequent triggers for diabetic ketoacidosis and a significant increase in morbimortality is observed in case of delayed antibiotic treatment. however the unnecessary administration of antimicrobial therapy can also lead to bacterial resistance. early sepsis markers are thus particularly useful for patients admitted in icu for diabetic ketoacidosis. patients and methods: we retrospectively studied cases of patients admitted in icu at avicenne french universitary hospital for ketoacidosis defined by ph < . and glycemia > . mmol l. clinical and biological data were analyzed at admission (d ) and on day (d ). results: between and , among patients admitted for diabetic ketoacidosis, were included. twelve out of were infected ( urosepsis, pneumonia, others). demographic data and comorbidities did not significantly differ between the infected and non infected group (ig and nig). antibiotics were administered to patients- ( %) in the infected group versus ( . %) in the non infected group. on d , there was no difference for-ph, temperature, leukocytes, neutrophils-to-lymphocytes count ratio and pct (table ) . on d , temperature, leukocytes, neutrophils-to-lymphocytes count ratio and pct were significantly higher in the ig. in the ig, the biological markers did not vary between d and d , whereas in the nig, leukocytes (p < . ), pnn (p < . ) and neutrophils-to-lymphocytes count ratio (p < . ) significantly decreased. surprisingly average pct levels seem to be particularly high in the nig on do as well as on d . conclusion: at admission, pct as well as other usual markers do not appear to be useful to differentiate infected from non infected patients admitted for ketoacidosis. however, on day , two different patterns can be drawn and help detecting non-infected patients and thus reduce exposure to antibiotics. these results should be confirmed by a prospective study, including a larger number of patients. ventilator-associated events (vae), reflecting worsening oxygenation, are defined as a persistent and significant increase in fio or peep level after a period of stability on the ventilator. vae definition includes ventilator-associated conditions (vac), infection-related ventilatorassociated complications (ivac) and probable ventilator-associated pneumonia (pvap). the relevance of vae for ventilator-associated pneumonia (vap) is low. however, the correlation between the three vac, ivac, and pvap, and the onset of ventilator-associated low respiratory tract infection (valrti), including ventilator-associated tracheobronchitis (vat) and pneumonia (vap), has never been studied yet. we on clinical examination. gravity scores-apache ii and saps ii. for lumbar puncture data, there is the proteinuria, glycorrhaphy resuscitation measures-drug intake and intubationin multivariate analysis, the factors of pejorative evolution-the male sex presence of meningeal syndrome. high proteinorachia. taking vasoactive drugs. the saps ii score. conclusion: according to this work, many factors influence the prognosis of acute meningitis in our population such as severity general scores, hemodynamic state and initial lumbar puncture data. we will need more investigations and prospective multicentric study to have more discrimination parameters. introduction: the emergence of atb-resistant bacteria has become an important public health problem, particularly in resuscitation environments, surveillance and monitoring of atb consumption is essential to combat this threat ecologically and economically. the aim of this work was to evaluate the consumption of atb in surgical resuscitation, to establish the cost, and to list the risk factors for bacterial resistance. patients and methods: it is a retrospective analytical study spread over year, studying patients who have received antibiotic therapy, the data on the consumption of atb were collected from the patient's medical records, the delivered doses were converted into ddd, according to the who standards and the end result is expressed in ddd days of hospitalization. the statistical analysis was carried out by the spss software. results: in our study, the mean age was . ± . , with male predominance + sex ratio . , traumatic pathology is the most common reason for admission, pneumopathy was the most frequent infection. overall atb consumption was . ddd dh, dominated by the class of betalactamins (cephalosporins . ddd dh, carbapenemes . ddd dh), the direct cost of atbs rises to . million dirhams, these are accounting for a large part of the pharmaceutical budget of the ibn rochd university hospital. bacteria found in order of frequency were acinetobacter baummanii, beta-lactamaseproducing enterobacteria, s. aureus and p. aeruginosa. acinetobacter baumannii showed the highest resistance rate. several risk factors for bacterial resistance were studied, notably the correlation between the use of atb and the emergence of resistant strains, only piperacillintazobactam was associated with the emergence of resistant strains of eblse, as well as other factors that were retained as significantly related to bacterial resistance by multivariate analysis-duration of hospitalization and perfusion of albumin. discussion: despite the limited number of studies done on atb consumption, it seemed that our results were similar to other national and foreign studies, the consumption of atbs is increased in hospital giving rise to the appearance of many multi-resistant bacteria. conclusion: in conclusion, resistance to antibiotics is a serious threat to public health both nationally and globally. it is therefore crucial to implement measures to counter this phenomenon + this is only possible through the proper use of atbs and gaits to prevent nosocomial infections. introduction: ventilaor-associated pneumonia (vap), the leading cause of infection in resuscitation, is also the main respiratory complication in cranial trauma. the aim of this study is to determine the specific risk factors for the occurrence of vap in this type of patient in an intensive care unit. patients and methods: we performed a retrospective study in our intensive care unit for an -month period (january , june ). all patients admitted for cranial trauma were included in the study and ventilated more than h in intensive care. vap is defined as late as of the th day of occurrence. the quantitative and qualitative variables studied were recorded at admission and during hospitalization. a univariate and multivariate analysis using the fischer and mann-whitney tests was performed. p is said to be significant if it is < . . results: our study included traumatic brain injury in older adults, of whom ( %) had one or more episodes of vap during their resuscitation. late vap accounted for almost of the cases ( patients). four independent variables were significantly related to the occurrence of vap-advanced age (p = . ), glasgow score (gcs) at admission < (p = . ), diabetes (p = , ), and the use of proton pump inhibitors for the prevention of stress ulcers (p = . ). the duration of intubation ( ± vs. ± days) and on intensive care ( ± vs. ± days) are significantly longer in the case of vap. mortality was significantly higher in vap- versus % (p = . ). the majority of early vap were due to both strepococcus ppneumoniae and haemophilus influenzae. the ecology of late vap was dominated by klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumanii. conclusion: of the four independent risk factors found in our study, glycemic balance and rapid airway safety by orotracheal intubation in the case of initial gcs < represent the relevant prevention axes of vap in traumatic brain injury in older adults. unfortunately, it is accompanied by a significant increase in bacterial resistance to antibiotics, leading to an increase in morbidity and mortality in intensive care units. patients and methods: this is a retrospective study carried out in our intensive care unit, covering all patients hospitalized between january and june and having contracted a nosocomial urinary infection. patients whose hospital stay was less than h and those fig. agreement between vae and lrti diagnostic with a nosocomial urinary tract infection acquired in another service were excluded. results: the study of resistance of the germs responsible for nosocomial urinary tract infection showed that-escherichia-coli was resistant to third generation cephalosporins in % of cases, at imipenem in % of cases, and without resistance to ertapenem and amikacin. pseudomonas was resistant to ceftazidime in % of cases, to imipenem in % of cases and to amikacin in % of cases. acinetobacter baumannii was resistant to imipenem in % of cases and to amikacin in % of cases. enterococcus faecalis had no resistance to vancomycin and ampicillin. staphylococcus aureus was resistant to methicillin in % of cases and without any resistance to vancomycin. mortality directly associated with nosocomial urinary tract infection was %. the comparison with previous studies has shown a significant increase in the bacterial resistance responsible for nosocomial urinary tract infection, which is of interest in monitoring the ecology of intensive care units and the resistance profile as well as the improvement of the management of antibiotics. introduction: nosocomial enterococcus infections are a constant concern in intensive care units due to their increasing frequency and the emergence of resistant strains to vancomycin. the aim of our study was to compare outcome findings of patients with nosocomial enterococcus infections according to their sensibility to vancomycin, and then to investigate predictive factors of mortality. patients and methods: it was a retrospective descriptive study, including all hospitalized patients in intensive care, between january st, and april st, , with nosocomial enterococcus infections. we recorded demographic and clinical findings, severity scores igs ii, apache ii, initial sofa and sofa at the time of infection, microbiological, therapeutic and outcome data. patients infected with vancomycin-susceptible enterococcus (vse) were compared to those having vancomycin-resistant enterococcus (vre) + then we searched for independent risk factors for vre. finally, a multivariate logistic regression was conducted to investigate independent predictive mortality factors. results: during the study period ( years and months), patients presented a nosocomial enterococcus infection with a median age of years [ - ] and a sex-ratio of . . at admission, patients ( . %) had respiratory distress. the median scores of igs ii, apache ii, initial sofa and sofa at the time of infection were respectively + + and . the infection sites were-urinary infection (n = , . %), bacteremia (n = , . %) and central line associated infection (n = , . %). patients had a vre nosocomial infections and vse. a septic shock complicated enterococcus infection in cases including cases of vre and cases of vse (p = . ). vre nosocomial infections were significantly related to arterial (p = . ) and venous (p = . ) femoral catheterization, to a duration of venous femoral catheterization > days (p = . ) and to e. faecium species (p < - ). no independent risk factor of vre was found. the median duration of hospitalization was days and the overall mortality rate was . %. multivariate analysis identified independent predictive factors of attributable mortality-patients in coma (or . + ic % = . - . + p = . ) and the occurrence of septic shock (or . + ic % = . - . + p = . ). conclusion: attributable mortality to nosocomial enterococcus infections was high and independent of the susceptibility of the strain to vancomycin. mortality was independently associated to septic schock occurrence and neurologic dysfonction. introduction: ventilator-associated pneumonia (vap) is defined by a lung infection contracted h after the putting under mechanically assisted breathing. risk factors predisposing to the development of vap among mechanically ventilated patients are many. some are related to the patient as age, history of copd, presence of an altered state of consciousness + others are related to care providing. patients and methods: a prospective nested case control study was conducted from marsh through april . all icu patients mechanically ventilated for more than h with endotracheal intubation or tracheostomy were included. cases of community-acquired pneumonia, non-mechanical ventilated hospital-acquired pneumonia, end-life patients and those aged less than years were excluded. the included patients with vap and those without vap were matched based on the age, the severity score and the comorbidities. for all patients included, preventive measures as assessed by the recent guidelines for preventing vap were applied after an education period of all medical and paramedical staff of the icu. the collected data are-age, comorbidities, admission severity scores, time to onset of vap, prior antibiotic therapy at the onset of vap, need for tracheostomy, duration of mechanical ventilation, length of stay in icu and become. results: during the study period, patients were mechanically ventilated. vap was observed in % of cases. vap was observed in cases with an incidence of % and incidence density of per patient-days of mechanical ventilation (mv). in univariate analysis, significant difference was found between the group with vap and the group without vap regarding admission for poly trauma, acute respiratory failure, the concept of prior antibiotic therapy, the need tracheostomy, the number of days alive without antibiotics and without mv, the duration of mechanical ventilation, length of stay and mortality. multivariate analysis showed that prior antibiotic therapy and the use of tracheotomy were independent factors for developing vap. prolonged duration of mechanical ventilation was an independent predictor of mortality in multivariate analysis with or . + % [ . to . ], p = . . the occurrence of vap was not an independent predictor to mortality. conclusion: the incidence of vap found in our study is similar to that found in the literature. an active strategy of rationalizing the prescription of antibiotics in intensive care units and a well-defined protocol of weaning from mechanical ventilation may reduce the incidence of vap and over-all morbidity and mortality. introduction: hyperoxemia is common in critically ill patients. hyperoxic acute lung injury (hali), reduced bacterial clearance, atelectasis and higher mortality rates were reported in mechanically ventilated patients with hyperoxemia. the aim of our study was to determine the relationship between hyperoxemia and mortality in patients with ventilator-associated pneumonia (vap). this retrospective observational single center study was performed in a -bed mixed intensive care unit (icu) during a -year period, from january to january . all patients with vap were included. vap was defined using clinical, radiological and quantitative microbiological criteria. hyperoxemia was defined as peripheral capillary oxygen saturation-spo ≥ %. spo was hourly collected in all study patients during the whole period of mechanical ventilation. the daily percentage of time spent with hyperoxemia was calculated as the number of hours with hyperoxemia divided by . results: among the patients receiving invasive mechanical ventilation (mv) > h during the study period, the incidence rate of vap was . vap per ventilator-days. patients developed vap and were all included in this study. ( %) vap patients died in the icu. the mean daily time spent with hyperoxemia was %. no significant difference was found in mean percentage of time spent with hyperoxemia between survivors and nonsurvivors at icu admission, before, after or at the vap diagnosis. age, and sequential organ dysfunction assessment (sofa) at the day of vap occurrence were independently associated with icu mortality (or . [ . - . ] per year, p = . + . [ . - . ] per point, p = . + respectively). no significant impact was found of time spent with hyperoxemia before vap occurrence, on mv free days, or icu length of stay (fig. ). discussion: several potential explanations could be provided for the absence of negative impact on mortality of hyperoxemia. first, the definition used for hyperoxemia could be debated, as no consensus exists. however, the definition used in our study was rather stringent and the mean daily time spent with hyperoxemia was in line with that reported by studies. second, the impact of hyperoxemia on mortality could have been confounded by a large number of patients included with pulmonary lesions at admission. third, the number of included patients was small. conclusion: our study found no significant impact of hyperoxemia at icu admission, or during icu stay, on icu mortality in vap patient. results: patients collected during this period. distal protected specimens were performed in patients suspected of vap. the diagnosis of this infection was made. in of them with other diagnostic criteria ( %) which represents an incidence density of . per , days. % of pavm are due to gram negative bacilli. the first germ involved in our series and pseudomonas ( %) followed by klebsielles ( %) followed by acintobacter baumanii ( %) enterobacteries representing the rest. % lung infection with gram-positive cocci (principally sensitive methicillin) pseudomonas was imipenem resistant in . %, baumanii was imipenem resistant in %. the resistance profile of the recovered germs (baumanii and pseudomonas) encourages the utmost rigor in the management of these patients, prevention is better attitude to adopt. introduction: the ventilator associated pneumonia (vap) appear in the second rank of the infections acquired in hospital after the urinary infections. the diagnosis is based on a beam of clinical, biological, radiological and bacteriological arguments. this work consisted of an epidemiologic analysis of the vap and aimed at evaluating of it the frequency, the risk factors, the antibioresistance of the isolated bacteria and the mortality factors. patients and methods: this retrospective study related to patients hospitalized in icu during a period of years from january to december . the study included all patients over years and ventilated more than h and developing vap. results: bgn predominant and represent . % of identified germs, the acinetobacter baumanni leads with . %, followed by klebsiella pneumonia ( . %), followed by pseudomonas aeruginosa ( . %), followed by e. coli ( . %), followed by enterobacter cloacae ( . %) and citrobacter frendi ( . %). the cocci gram positive (cgp) constitue . % of isolated germs of witch . % staphylococcus aureus, . % of non aureus staphylococci, . % streptococcus sp. the polymicrobism was found in % cases. the isolated germs were multiresistants. in this study, we find a very high mortality and a major additional morbidity of the np by prolongation of hospitalization, of mechanical ventilation and a major additional cost.conclusion: it appears in the light of this work that a strategy of prevention based on the strict application of hygiene measurements, the maintenance of the material of ventilation and the respect of care procedures prove to be urgent in our context. introduction: burns induce modification of distribution volume, increased clearance of drugs and decrease of protein binding. amikacin pharmacokinetics (pk) was altered with subthera-peutic serum concentrations. the aim of our study was to assess the pk of amikacin in burns after a loading dose given once a day according to this equation-dose(mg kg) = *pi( * , *dp ) + ( * , * dp ). threshold for therapeutic efficacy was a ratio of ≥ between the concentration achieved h after beginning the infusion (c peak) and the minimal inhibitory concentration (mic) of the isolated pathogen. patients and methods: this study was conducted in burn center in tunis. patients with documented and or suspected infections were included. were excluded pregnant women and patients with renal failure. enrolled patients received amikacin at a loading dose in h infusion. blood samples for pk analysis were assessed during days (total duration of amikacin)-immediately after the end of the first infusion (t ) and min after (t ) at day . for the nd, rd, th and th day, blood samples were taken before the infusion (t ), at the end (t ) and min after the end of it (t ). results: burned patients were included. the mean age was ± years with a body weight of ± kg. the mean dose of amikacin was mg kg day [ - mg kg day]. a peak between and μg/ml was reached in % of cases, corresponding to times the mic, break-points for enterobactericeae and pseudomonas aeuroginosa. total volume of distribution was . l kg ( . - . ) l kg, half-life time (t ) was . h [ . - h] and the amikacin clearance was . l h. a correlation was found between cpeak at day and cpeak at day (r = . ). conclusion: our study shows that an early achievement of an optimal cpeak mic ratio of amikacin was reached in half of cases with a correlation between cpeak in the beginning and at the end of treatment. so, initial cpeak was useful tu adjuste amk therapy in burns and predicts treatment efficacy. *pi-ideal weight + dp -admission weight-ideal weight + dp -actuel weight-admission weight. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -o hr mox authors: nan title: proceedings of réanimation , the french intensive care society international congress date: - - journal: ann intensive care doi: . /s - - - sha: doc_id: cord_uid: o hr mox nan rationale: expiratory muscles has recently been stated as the «neglected component» in mechanically ventilated patient. several authors stated these muscles importance in cough capacity, contractile efficiency of the diaphragm or reduction of hyperinflation. however, few studies reported potential factors leading to expiratory muscle weakness and its importance on weaning success or survival after mechanical ventilation. patients and methods: this study is a secondary analysis of our previously described cohort of patients ventilated for at least h assessed for respiratory muscles function. maximal expiratory pressure (mep) measurement was carried out during spontaneous breathing trial using a manometer with an unidirectional valve. mep diagnostic accuracy to predict icu-aw (icu acquired weakness), weaning success and sursvival within days were assessed using expiratory muscle strength as absolute values (cmh o), as %predicted values and as %lower limit of normal. results: due to the paucity of data reporting threshold value for expiratory muscle weakness, we considered our median value ( cmh o (iqr )) as the threshold value for expiratory muscle weakness group (mep ≤ cmh o) and normal expiratory muscle group (mep > cmh o). patients with low mep received more catecholamines (p = . ) and a higher duration of mechanical ventilation (p = . ). inversely, higher body mass index was associated with higher mep. patients with low mep presented more icu-aw compared to normal mep patients ( % vs. %; p = . ). no other outcomes were different between groups. mep was statistically able to predict icu-aw but area under (auc) receiving operating curves showed weak predictive ability (auc: . ( % ic . - . ; p < . ) for a threshold value ≤ cmh o. expiratory muscle weakness was unable to predict critical outcomes when adjusting mep to the %predicted or lower limit of normal. discussion: possible explanation is that contrary to inspiratory muscle weakness, cough inefficacy after weaning from mechanical ventilation could be managed with cough supplementation techniques (i.e. mechanical in-exsufflation). conclusion: in our cohort, mep was not associated with mechanical ventilation weaning or death. despite our results, different clinical techniques for quantifying expiratory muscle weakness may provide more beneficial results. compliance with ethics regulations: yes rationale: venoarterial extracorporeal membrane oxygenation (va-ecmo) is used to support tissue perfusion during extracorporeal cardiopulmonary resuscitation (e-cpr). shock, resuscitation and the extracorporeal circuit may trigger a capillary leakage and a vasoplegic shock. currently, in these situations, high doses of norepinephrine (ne) are required. because high ne doses may have significant cardiovascular side effects, alternative options to support arterial blood pressure are needed. in recent years, several approaches to decrease the administration of high ne doses have been tested, one of them is the administration of vasopressin (avp). randomized trials have shown that avp infusion increases arterial pressure and systemic vascular resistance, decreases catecholamine requirements in patients with or at high risk of vasoplegic syndrome and attenuates vascular dysfunction. currently, no data are available for the study of the effects of avp in shock state in post refractory cardiac arrest. patients and methods: pigs were randomized into two groups, in order to receive avp or ne. a refractory cardiac arrest of ischemic origin was surgically created and va-ecmo was started after a min period of cardio-pulmonary resuscitation. then, resuscitation lasted h in each randomization group. the evolution of the consequences of the shock was evaluated by lactatemia and microcirculation (sdf and nirs) at baseline hour, h (when ecmo starts), h and h . renal and hepatic functions were assessed. results: experimental conditions were met for animals (avp, n = ; ne, n = ). the groups were comparable on the shock impact and its severity. no significant differences were found between populations for ecmo flow and map. there was a significant difference on fluid volume resuscitation amount ( [ . - . ] ml in the ne group versus ml in the avp group, p < . ) (fig. ). no significant difference between the ne and avp groups for lactate clearance between h and h ( . [− . to . ]% vs . [ . - . ]%, p = . ). we did not find any significant for sublingual microcirculation indices and nirs values. renal and liver function evolution were similar in the two groups during the protocol. conclusion: avp administration in refractory cardiac arrest resuscitated by va-ecmo when compared to ne is associated with less fluid volume for similar global and regional hemodynamic effects. compliance with ethics regulations: yes. patients and methods: a single-center prospective study. patients younger than months with severe bronchiolitis and supported by niv or hfnc were included. niv/hfnc was discontinued according to the local practices and no protocol existed. exceptt the principal investigator, the attending team was blinded to the study. weaning failure was defined as the need to reinstate niv/hfnc in the h after discontinuation. ethical approval was not necessary for this study in accordance with the french data protection autority methodology reference number mr- . results: a total of patients (median age days, ( %) males) were included. respectively, ( %) and patients ( %) were supported by niv and hfnc at admission (fig. ) . regarding the mode of niv, a bilevel mode was used in patients ( %) (fig. ). in patients supported by hfnc, the ventilatory support was discontinued progressively by decreasing air flow in patients ( %) while it was stopped abruptly in ( %). in patients supported by niv, the respiratory support was stopped abruptly in ( %) of them while hfnc was used as a weaning method for ( %) patients. a total of ( %) patients experienced a weaning failure. patients supported by niv/ hfnc who experienced a prompt weaning had a lower pediatric intensive care unit (picu) length of stay as compared to patients in whom hfnc was used as a weaning method ( ± h versus ± h, p = . ). however, the hospital length of stay was similar according to the weaning method ( ± days versus ± days for prompt and progressive methods respectively, p = . ). the duration of the weaning process did not differ according to the bed-availability in picu. in patients with severe bronchiolitis, a prompt weaning from niv/hfnc was associated with a lower length of stay in picu. however, the hospital length of stay was similar according to the weaning method. we suggest that a prompt weaning should be preferred in order to reduce the risk of picu related complications. compliance with ethics regulations: yes. information and incitation to open a twitter account and to follow critical care journal feeds) or group (control group). ict were interrogated on their recent medical literature knowledge at and month on trials published in pre-selected journals. results: during the study period, on the french ict contacted, agree to participate: were already on twitter, were randomized to twitter incitation and to control group. at month, there were who answered electronic questionnaire. self-declaration of article knowledge was not different between groups (p = . ). knowledge of primary outcome of each trial was not significantly better in groups (p = . ). in per-protocol analysis of ict on twitter or not, knowledge of article and primary outcome were also not significantly different (respectively p = . and p = . ). short incitation to open a twitter account and follow major medical journals with specific focus on cardiac arrest did not improve knowledge of medical literature by intensive care trainees at month. further trials are needed to better imply intensive care trainees in scientific medical literature. compliance with ethics regulations: yes. - . ] ; p = . ) as independently associated with in-hospital mortality ( fig. ). discussion: triple therapy is the recommended first-line treatment of caps. however, herein, it was not significantly associated with better survival in critically ill, thrombotic aps patients. for the subgroup of "definite/probable caps" patients, double and triple regimens were associated with survival. but the bivariable analyses including the day- saps ii showed that survival was linked to in-icu anticoagulation and corticosteroids-not ivig or plasmapheresis. our findings indicate that corticosteroids should probably be added to in-icu anticoagulation to treat "definite/probable caps". frequent fever and elevated c-reactive protein in all thrombotic aps patients suggest a marked inflammatory state that could explain corticosteroid efficacy. neither plasmapheresis nor ivig impacted the prognosis of "definite/ probable caps", but that finding could be explained by a lack of power compared to caps registry data. conclusion: in-icu anticoagulation was the only aps-specific treatment independently associated with survival for all patients. doublebut not triple-therapy was independently associated with better survival of "definite/probable caps" patients. in these patients, double therapy should be used as first-line therapy while the role of triple therapy requires further evaluation. compliance with ethics regulations: yes. motor deficiency ( %) ( %) ( %) . cognitive impairment ( %) ( %) ( %) . intra-individual relationships between Δpdi and tfdi for mechanically ventilated (mv) patients (a) and healthy subjects (c). relationships between Δpdi and tfdi when breathing cycles were averaged for all participants during each condition for mv patients (b) and healthy subjects (d). − %: initial settings minus % inspiratory help, + %: initial settings plus % more inspiratory help, pep : zero positive end-expiratory pressure, sbt: spontaneous breathing trial. healthy subjects performed spontaneousbreathing (sb) and ventilation against inspiratory threshold at , , , and % of maximal inspiratorypressure (mip) groups. airway closure occurrence increased with bmi ( %, % and %, p = . ). when present, airway opening pressure was . cmh o ( . - . ) and similar between the groups. with increasing bmi, total peep increased from . to . cmh o between groups (p = . ). all values of esophageal pressure increased with bmi. endexpiratory esophageal pressure was strongly correlated with bmi (rho = . , p < . ), as illustrated in fig. . consequently end-expiratory transpulmonary pressure decreased from − . to − . cm h o with increasing bmi (p = . ). the ratio of eelv to predicted functional residual capacity was negatively correlated with end-expiratory pressure (rho = − . , p = . ), but not with bmi. driving pressure and elastance of the respiratory system, chest wall and lung were similar across all ranges of bmi. likewise, eelv was similar between groups. conclusion: in ards, increasing bmi is associated with increased occurrence of airway closure and increased values of esophageal pressure. conversely, chest wall elastance is not influenced by bmi, as well as lung elastance. including bmi in interpreting respiratory mechanics in ards patients can provide additional information for the clinical management. compliance with ethics regulations: yes. rationale: low tidal volume is the cornerstone of protective ventilation inthe initial phase of ards ( ) . whether such low tidal volume can still be achieved when the patient is allowed to breathe spontaneously under pressure support ventilation (psv) is unknown. in moderate-tosevere ards patients receiving neuromuscular blockade, we assessed the tidal volume and its potential association with the outcome during the "transition period" following neuromuscular blockade. patients and methods: retrospective observational study in two university intensive care units. patients fulfilling moderate-to-severe ards criteria less than h after intubation and receiving neuromuscular blockers were included upon entry in the "transition period". we defined the "transition period" as the h following neuromuscular blockers cessation. ventilatory and hemodynamic parameters were recorded every h during the "transition period". primary outcome was the association between mean tidal volume under pressure support ventilation (psv) during the "transition period" and the -day mortality after adjustment for confounding factors. data are reported as median [ st- rd quartile] or number (percentage). results: one hundred nine patients were included, with a pao /fio ratio of mmhg at intubation and mmhg at inclusion and a sofa score at [ . - ] . patients had been ventilated days [ - . ] before inclusion. during the "transition period", patients ( . %) were switched to psv. the median duration of psv was h . the mean tidal volume under psv was significantly lower in survivors than in non survivors at day ( . ml/kg [ . - . ] vs. . ml/kg [ . - . ] respectively, p = . ). by multivariate analysis (cox proportional hazards regression model), mean tidal volume during psv remained independently associated with the -day mortality after adjusting for sofa score and immunosuppression. patients with a mean tidal volume above ml/kg under psv during the "transition period" had a lower cumulative probability of survival at day as compared with others (log rank test, p = . ) (fig. ) . conclusion: in patients with moderate-to-severe ards, a higher tidal volume under psv within the h following neuromuscular blockers cessation is independently associated with the -day mortality.compliance with ethics regulations: yes. kaplan-meier estimate of the cumulative probability of survival according to the mean tidal volume (vt)-lower of higher than ml/ kg-under pressure support ventilation (psv) during the "transition period" transfusion is associated with adverse events, and equipoise remains on the optimal transfusion strategy in oncologic patients in surgical setting. patients and methods: this is a retrospective, single center study. all adults admitted to the intensive care unit (icu) after oncologic surgery from january to december were eligible. the following types of surgery for cancer or metastasis resection with a high risk of bleeding were eligible: thoracic, abdominal, neurosurgery, gynecologic, urologic, otorhinolaryngology or spinal surgery. the primary outcome was a composite outcome including post-operative complications (respiratory, cardiac, renal, thromboembolic, infectious and/or hemorrhagic) and/or hospital mortality. results: of the patients included, patients ( . %) had anemia (based on the who definition: hemoglobin level - . g/dl for female; hemoglobin level - . g/dl for male), patients ( %) had moderate anemia (hemoglobin level: - . g/dl) and patients ( . %) severe anemia (hemoglobin level < g/dl). fifty-six patients ( . %) received at least one rbc transfusion during their hospital stay. patients exposed to moderate and severe anemia required more often renal replacement therapy (rrt) for acute kidney injury (aki) ( . % vs. . %; p = . ), had more surgery-related infections ( . % vs. . %; p = . ). patients who received rbc had more often aki with rrt ( . % vs. . %; p < . ), thromboembolic events ( . % vs. . %; p = . ), sepsis ( . % vs. . %; p = . ), pneumonia ( . % vs. . %; p = . ), surgical site infections ( . % vs. . ; p < . ) and second surgery for infection ( % vs. . %; p = . ). the multivariate analysis found an association between moderate and severe anemia (moderate anemia: or . [ . - . ] ; severe anemia: or . [ . - . ]; p = . ) and severe post-operative complications (fig. a) . there was also an association between rbc transfusion and severe post-operative complications ]; p < . ) (fig. b) . conclusion: anemia was frequent in oncologic surgical patients. anemia, including moderate anemia, was independently associated to patient outcomes; however, rbc transfusion also negatively impacts on patients' prognosis. our study highlights the need for further research to identify the optimal hemoglobin threshold for rbc transfusion in surgical oncologic patients. compliance with ethics regulations: yes. rationale: right ventricular (rv) failure is a common complication in moderate to severe acute respiratory distress syndrome (ards). rv failure is exacerbated by hypercapnic acidosis and overdistension induced by mechanical ventilation. veno-venous extracorporeal co removal (ecco r) might allow ultraprotective mechanical ventilation strategy with a low tidal volume (vt) and plateau pressure (pplat). this study investigated if ecco r therapy could have beneficial effects on rv function. patients and methods: this prospective monocentric pilot study was conducted in a french icu from january to march . patients with moderate to severe ards with pao /fio ratio between to mmhg were enrolled. ventilation parameters, arterial blood gases, echocardiographic parameters performed by transthoracic echocardiography (tte), low-flow ecco r system operational characteristics, outcomes and adverse events were collected during the protocol. primary end point was evolution of rv echocardiographic parameters with ultraprotective ventilation strategy at ml/kg pbw during the -h following the start of ecco r. results: eighteen patients were included. efficacy of ecco r allowed an ultraprotective strategy in all patients. we observed a significant improvement of rv systolic function parameters assessed by tte (fig. ). tricuspid annular plane systolic excursion (tapse) increased significantly under ultraprotective ventilation compared to baseline (from . to . mm; p < . ). systolic excursion velocity (s') also increased after -day protocol (from . m/s to . m/s; p < . ). a significant improvement of aortic velocity time integral (vtiao) under ultraprotective ventilation settings was observed. there were no significant differences in the values of systolic pulmonary arterial pressure (spap). when patients were separated in two groups according to baseline paco level above or under mmhg, we showed the deleterious effect of hypercapnia on rv function, and observed in both groups a beneficial impact of an ultraprotective ventilation strategy on tapse. no severe adverse events directly related to ecco r were observed in our small cohort. conclusion: the low-flow ecco r allows ultraprotective ventilation strategy and improve rv function in moderate to severe ards patients. similarly to prone positioning, ecco r could become a strategy that enables to reconcile lung protective approach with rv protective approach in ards patients. large-scale clinical studies, including patients with severe rv dysfunction, will be required to confirm these results and to assess the overall benefits, in particular the best timing of beginning ecco r in ards patients. compliance with ethics regulations: yes. rationale: bronchoalveolar lavage (bal) is usually deemed to allow the diagnosis of a large array of pulmonary diseases and is usually considered as well tolerated in intensive care unit (icu) patients. however, recent data suggest that the diagnostic yield of bal could be rather low ( ) , and may question its innocuity ( ) . the present study aimed at assessing the benefit-to-risk balance of bal in icu patients. patients and methods: the study was approved by the appropriate ethics committee and registered with clinicaltrials.gov (nct ). in icus, from april to october , we prospectively collected adverse events (ae) during or within h after bal and assessed the bal input for decision-making in consecutive adult patients. aes were categorized in grades of increasing severity. the occurrence of a clinical ae at least of grade , i.e. sufficiently severe to need therapeutic action (s), including modification (s) in respiratory support, defined poor bal tolerance. the bal input for decision-making was declared satisfactory if it allowed to interrupt or initiate one or several treatments. results: we included bal in patients (age yrs ; female gender: [ . %]; simplified acute physiology score ii: ; immunosuppression [ . %], chronic pulmonary disease [ / ( . %)]). bal was performed either in non-intubated patients receiving standard o therapy (n = [ . %]), or noninvasive ventilation (n = [ . %]), or high-flow nasal cannula o therapy ( [ . %]), or in patients under invasive mechanical ventilation (n = [ . %]). a total of aes were observed in ( . %) patients. sixty-seven ( . %) patients reached the grade of ae or higher. the main predictor of poor bal tolerance identified by logistic regression was the association of a bal performed by a non-experienced physician (non-pulmonologist, or intensivist with less than years in the specialty or less than bal performed) in non-intubated patients (or: . [ % confidence interval . - . ] ; p < . ). ordinal regression also showed that when bal was performed by a non-experienced physician in a non-intubated patient, this was associated with an increased risk of ae of any grade (or: . [ . - . ]). a satisfactory bal input for decision-making was observed in ( . %) cases and was not predictable using logistic regression. conclusion: adverse events related to bal in icu patients are frequent, and sometimes serious. our findings call for an extreme caution when envisaging a bal in icu patients and for a mandatory accompaniment of the less experienced physicians. compliance with ethics regulations: yes. meningitis is a rare complication of critically ill patients with severe pneumococcal community-acquired pneumonia paul jaubert, julien charpentier, jean-daniel chiche, frédéric pene, alain cariou, guillaume savary, marine paul, jean-paul mira, mathieu jozwiak cochin, paris, france; mignot, versailles, france correspondence: paul jaubert (paul.jaubert@gmail.com) ann. intensive care , (suppl ): rationale: severe pneumococcal community-acquired pneumonia (pcap) is a frequent infection requiring intensive care unit (icu) admission. pneumococcal meningitis associated with pcap has been reported and could worsen the prognosis of patients. however, this complication is difficult to predict and lumbar puncture is not systematically performed, regardless the severity of pcap. thus, we investigated the characteristics of patients with pcap associated with pneumococcal meningitis. patients and methods: we retrospectively included all patients admitted for pcap in our icu between (inception of our electronic medical sheet) and the end of . community-acquired pneumonia was defined according to the criteria of the american thoracic society. we excluded all patients admitted in icu with initial suspicion of meningitis. variables regarding epidemiology, clinical and microbiological characteristics, management and prognosis of these patients were collected and analyzed. results: among the patients admitted for pcap ( ± years old, saps ii ± , % of men), % of the patients required mechanical ventilation and % vasopressors infusion. the icu mortality was %. s. pneumoniae was documented by a positive antigen test in % of the patient and/or by a positive sputum smear, tracheal aspirate or distal protected airway specimen in % of the patients, and/or by pleural aspirate in % of the patients and/or by positive blood culture in % (n = ) of the patients. a lumbar puncture was performed in % (n = ) of the patients with bacteriemia and in % (n = ) of the patients without bacteriemia, with a median delay of h [interquartile range: after the onset of antibiotherapy. alllumbar punctures (n = ) were performed for neurological signs: % of coma, % of confusion and % of seizures. when a lumbar puncture was performed, meningitis was diagnosed in % (n = ) of the patients with bacteriemia and in % (n = ) of the patients without bacteriemia (p < . ). the icu mortality ( % vs. %, respectively), age ( ± vs. ± years old, respectively), saps ii ( ± vs. ± , respectively) or icu length of stay ( ± vs. ± days, respectively) were not different between patients with and without meningitis (each p = ns). conclusion: meningitis is a rare complication of pcap and is more frequent in patients with bacteriemia. suprisingly, meningitis is not associated with higher icu mortality. further analyses are ongoing to identify independent risk factors of meningitis in patients with pcap. compliance with ethics regulations: yes. rationale: shock is the clinical expression of a circulatory failure that results in inadequate cellular oxygen utilization. whereas the host response to septic shock has been extensively described, knowledge of the pathogenesis of non-septic shocks remains limited. we aimed to characterize the systemic host response in shock related to non-septic conditions (nssh) as compared with septic shock (ssh). patients and methods: we performed a prospective study in two intensive care units (icus) in patients admitted for ssh (n = ) or nssh (n = ). immune responses were determined upon icu admission by measuring plasma biomarkers reflecting host response pathways implicated in the pathogenesis of critical illness (in ssh and nssh patients), and by applying genome-wide blood mrna expression profiling (in ssh and nssh patients). results: compared with nssh, patients with ssh had more chronic comorbidities, greater disease severity (apache iv score vs. , p < . ) and worse outcomes resulting in higher mortality rates up to one year after icu admission ( . % vs. . %, p < . ). plasma biomarker analysis revealed severely disturbed host responses in both ssh and nssh patients. however, ssh patients displayed more prominent inflammatory responses, endothelial cell activation, loss of vascular integrity and a more pro-coagulant state relative to nssh patients. blood leukocyte genomic responses were more than % common between ssh and nssh patients relative to health (fig. a) , comprising overexpression of innate pro-and anti-inflammatory pathways, and underexpression of lymphocyte and antigen-presentation gene sets. direct comparison of ssh to nssh patients matched for severity (fig. b) showed overexpression of genes involved in mitochondrial dysfunction and specific metabolic pathways, and underexpression of lymphocyte, nf-κb and cytokine pathways. conclusion: patients with ssh and nssh present with largely similar host response aberrations at icu admission; however, patients with septic shock show more dysregulated inflammatory and vascular host responses, as well as specific leukocyte transcriptome alterations consistent with greatermetabolic reprogrammingand more severe immune suppression. compliance with ethics regulations: yes. rationale: aki is associated with short and long term mortality and morbidity. although recovery has been demonstrated to be associated with outcome of critically ill patients, interpretation of available data is limited by time dependent nature of recovery and by competing risks. our objective was to describe renal recovery, pattern of recovery according to adqi definitions and risk factor of this later. monocenter retrospective cohort study. adult patients admitted in our icu from july to december were included. aki was defined according to kdigo criteria and recovery according to adqi definition. incidence of recovery at each time point was depicted using competing risk survival analysis. risk of transition between aki and no-aki was assessed by a semi-markov model. last, a trajectoire analysis was performed to depict most frequent recovery patterns. results are reported as n (%) or median (iqr). results: patients were included with a median age of ( - ). median sofa score at admission was [ ] [ ] [ ] [ ] [ ] [ ] . at icu admission, patients ( . %) had an aki stage , patients ( . %) an aki stage and patients ( . %) an aki stage . according to adqi criteria, aki was defined as rapidly reversed in patients ( . % of aki patients), persistent aki in patients ( . %) and as acute kidney disease (akd) in patients ( . %), remaining patients couldn't be classified (n = ). risk of recovery was of % per day until day then % per day (fig. a) . fine and gray model, taking into account death as competing risk, identified risk factors negatively associated with renal recovery, namely sofa score (shr = . per point; % ic = [ . - . ]), preexisting hypertension (shr = . ; % ic = [ . - . ]) and aki severity (stage vs. stage shr = . ; % ic = [ . - . ]). risk of de novo aki was maximal during the first days and ranged from to % per day. trajectoire model identified clusters of patients ( fig. b) , closely associated with patients' outcome: a) low patients' severity and no or mild aki (n = ; hospital mortality: %); b) moderate to severe aki but little associated organ dysfunction (n = , hospital mortality: . %); c) severe aki and multiple organ failure (n = ; hospital mortality: . %). conclusion: this study, assessing aki recovery patterns, is the first to our knowledge using adqi definition. despite the high rate of early recovery and of rapidly reversed aki, up to % of aki patients had not recovered at day and could therefore be classified has having akd. compliance with ethics regulations: yes. rationale: sepsis is the most frequent cause of acute kidney injury (aki). the "acute disease quality initiative workgroup" recently proposed new definitions for aki, classifying it as transient or persistent. we aimed to determine the incidence, attributable mortality and host response characteristics of transient and persistent aki in patients with sepsis. patients and methods: we performed a prospective observational study comprising consecutive admissions for sepsis in intensive care units (icus) in the netherlands, stratified according to the presence and evolution of aki. attributable mortality fraction (excess risk for dying with persistent aki relative to transient aki) was determined using a logistic regression model adjusting for confounding variables. in a subset of sepsis patients, plasma biomarkers indicative of major pathways involved in sepsis pathogenesis were measured. in a second subset of patients, whole-genome blood-leukocyte transcriptomes were analyzed. results: sepsis patients were included. aki occurred in . % (n = ), of which . % (n = ) was transient and . % (n = ) persistent. patients with persistent aki had higher disease severity scores on admission than patients with transient aki or without aki and more frequently had severe (injury of failure) rifle aki-stages on admission (n = , . %) than transient aki patients (n = , . %, p < . ). persistent aki, but not transient aki, was associated with increased mortality by day- (adjusted or . , % ci . - . ; p = . ) ( figure) and up to -year (adjusted or . , % ci . - . ;p = . ). the attributable mortality of persistent relative to transient aki by day- was . % ( % ci . - . %). persistent aki was associated with enhanced and sustained inflammatory and procoagulant responses during the first days, and a more severe loss of vascular integrity compared with transient aki. baseline blood gene expression showed minimal differences with respect to the presence or evolution of aki. conclusion: persistent aki is associated with higher sepsis severity, sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient aki, and independently contributes to sepsis mortality. compliance with ethics regulations: yes. rationale: to address the paucity of data on the epidemiology of patients admitted to intensive care units (icus) with in-hospital cardiac arrest (ihca), we examined key features, mortality and trends in mortality in a large cohort of patients admitted in french icus over the past years. patients and methods: from to database of the collège des utilisateurs de bases de données en réanimation (cub-réa), we determined temporal trends in the characteristics of ihca, patients' outcomes and predictors of icu mortality. results: of the icu admissions, ( . %) were cardiac arrests and were ihca ( . %). during the study period, the age of ihca patients increased by . years (p = . ) and patients presented more comorbidities (chronic heart disease, chronic kidney disease and cancer). patients were also more critically ill over the period as reflected by the increase of saps-ii by . % (p < . ). paradoxically, in-hospital management became lighter through the time with reduced respiratory support (p < . ), renal support (p < . ) and use of vasoactive drugs (p < . ). crude in-icu mortality decreased from % to . % over the past eighteen years (p < . ), fig. rationale: in surgery, prophylaxis antibiotic aims at preventing the occurrence of post-operative infections. for adults, it is currently recommended to only use prophylactic antibiotic therapy during the time of the intervention. but in pediatric cardiac surgery, there is no consensus around the optimal duration of use of antibiotic prophylaxis. the protocol was modified in in the icu and its time reduced to h. we aimed to determine whether h of post-sternotomy antibiotic prophylaxis was not less effective than h treatment to help prevent care-associated infections. patients and methods: after agreement of the ethics committee of our institution, we performed a retrospective non inferiority study, with an inferiority margin to %. the primary objective is to compare the incidence of care-related infections between a second-generation cephalosporin (c g) antibiotic prophylaxis during h and a -h protocols. the secondary objectives are to determine the infection's incidence, to identify the risk factors for nosocomial infections and to compare the incidence of multidrug-resistant infections. results: between january and july , children underwent cardiac surgeries with sternal opening. received h of c g antibiotic prophylaxis and received h of c g treatment. five previously infected children have been excluded. both groups were demographically and surgically similar. the median age was months (range a few hours of life to . years old) and the median weight was . kg. in the intent-to-treat analysis, incidence of care-related infections is at . % in the c g- h group and . % in the c g- h group. a multivariate analysis shows that the shorter -h time antibiotic prophylaxis is not inferior regarding infection prevention compared to h of antibiotic prophylaxis, p = . . as in the per protocole analysis, the c g- h group rate was . % and . % for the g g- h group. conclusion: it demonstrates that shortening the antibiotic prophylaxis treatment time to h does not affect or increase the rate of infections after a pediatric sternotomy surgery compared to -h protocole. prophylaxis in pediatric cardiac surgery should be short-lived. a multicenter prospective study would allow a consensus and confirm this decision. compliance with ethics regulations: yes. rationale: the use of "big data" is getting increasingly popular in the medical field, especially in intensive care where large amounts of data are continuously generated. however, big data can be misleading when essential clinical data are missing. the adequate adjustment for potential confounding factors (e.g., severity of respiratory distress) should be the key procedure in the big data analyses; however, it is challenging to capture the clinical severity within large electronic databases. bronchiolitis is one main reason for admission to pediatric intensive care unit (picu). the modified wood's clinical asthma score (mwcas) is widely used to assess the severity of bronchiolitis. the objective of the study is to build an automated mwcas (a-mwcas) to continuously assess the severity of respiratory distress in critically ill children. this retrospective study included all infants < years old with a clinical diagnosis of bronchiolitis, ventilated with non-invasive neurally adjusted ventilatory assist, in a canadian picu, between october and june . we developed an algorithm, using python . , which was directly connected to the electronic medical record. the components of the score were collected using structured query language (sql) queries and processed to derive the a-mwcas. for validation, the a-mwcas score was compared to the mwcas manually computed by a clinical expert (m-mwcas) . results: sixty-four infants were included in the study, for which of a-mwcas and m-mwcas were generated respectively. the cohen's kappa coefficient was applied to estimate the agreement between the two scores which was . ( % confidence interval) ( table ) which corresponds to . % of complete agreement. . % of the a-mwcas scores were within ± . of the m-mwcas. the kappa coefficient for the each score component were: . for the oxygen saturation, . for the expiratory wheezing, . for the inspiratory breath sounds, . for the use of accessories muscles and . for the mental status, respectively. discussion: the largest discrepancy was observed in the mental status, which clinical evaluation is relatively subjective and varies among care team members (doctor, nurse, respiratory therapist…). the automated score likely decreases this variability by consistently using the same source (respiratory therapist), but its validity should be confirmed in a prospective study. the a-mwcas provides a valid estimation of the mwcas that is fast and robust. after external prospective validation, it may help to add some clinical sense within large electronic databases, with improved assessment of the respiratory distress. compliance with ethics regulations: yes. rationale: in paediatric intensive care units (picu), survival rates have dramatically improved. this has been accompanied by increased morbidity, including psychological morbidity. these new impairments, that can affect the survivors and their families have been conceptualized under the frame of post-intensive care syndrome (pics) and picsfamily. the aim of this study was to explore the experience of critically ill children parent's during the stay in picu, and its impact on the family. patients and methods: we planned a prospective, single centre study for months. we collected qualitative written data from parents whose child had been admitted to the picu for the first time, for at least two nights. results: fifty-seven questionnaires were analysed from thirty-seven admissions. picu admissions were mostly unplanned. among parents % experienced very painful memories during admission and % have feared for their child's life. during the stay, noise has bothered % of parents, and many have described difficulties to rest at night. % had the sensation that their child was suffering, mostly from pain, tiredness, anxiety or fear. during picu stay, % of parents had to stop working, and siblings schooling was impacted in % of cases, % of parents considered themselves to be useful for their child and % have participated to nursing care. more than % were satisfied about information given and communication, % appreciated empathy and support from care givers. parents received support from family, friends, and also from other parents of hospitalized children. parents expressed relief ( %) and serenity ( %) to leave picu, % of them were in demand to meet picu staff again after discharge. conclusion: picu parent's experience is tough, and the impact on family is clear. these are known risks factors for pics. on a very positive note, parents seemed to be satisfied by family-centred care, and were able to preserve their parental role. however, there is still room for improvement of practices. compliance with ethics regulations: yes. the gut has been suspected to be involved in multiple organs dysfunction syndrome (mods) in the intensive care unit (icu). studies suggested a link between gastrointestinal dysfunction (gid) and outcomes. but these studies included very few patients and most of them were retrospective. patients and methods: this study is a secondary analysis of data from a previous study that included patients from french icus. gid is defined as the association of vomiting and constipation or diarrhea during the first week after icu admission. patients included were treated with vasopressors and mechanical ventilation. the first goal was to determine if gid is a risk factor of -day mortality in this population. secondary goals were to assess the impact of gid on nosocomial infections. results: among included patients, ( . %) had gid. by day- , ( %) of the patients with gid and ( %) of the patients without gid had died (odds ratio . [ . - . ]; p = . ). multivariable regression model did not show any association between gastrointestinal dysfunction and increased risk of -day mortality in patients (odds ratio . [ . - . ], p = . ). gastrointestinal dysfunction was strongly associated with other secondary outcomes ( table ). patients with gid had longer ventilation duration, icu length of stay and hospital length of stay. they also had more nosocomial infections, in particularly ventilator-associated pneumonia. this association still existed in a multivariable regression model for prediction of nosocomial infection including the same variables than the previous model (odds ratio . [ . - . ], p = . ). no association with day- mortality was observed. conclusion: gastrointestinal dysfunction was not a risk factor of day- mortality but was associated with an increased risk of nosocomial infection and an increased length of stay. this study is observational and no causality link can be done. however, our data suggest further studies on strategies aimed to limit gid. compliance with ethics regulations: yes. rationale: acute cholangitis (ac), a bacterial infection related to an obstruction of the biliary tree, may be responsible for life-threatening organ failure. however, little is known about the outcome and the predictive factors of mortality of critically ill patients admitted in icu for acute cholangitis. we aimed to describe characteristics of patients admitted in icu for ac and to analyze predictive factors of in-hospital mortality including the time to biliary drainage procedure. patients and methods: retrospective study of all cases of acute cholangitis admitted in french icus ( tertiary hospitals and non-ter- [ . ; . ] µg/l. % of patients (n = ) have positive blood culture, mostly gram negative bacilli ( %) and % producing extended spectrum beta lactamase enterobacteriaecae. at icu admission, persisting obstruction was frequent ( %) and therapeutic endoscopic retrograde cholangiopancreatography was performed in % of them. in a multivariable analysis, at icu admission, several factors were significantly associated with in-hospital mortality: sofa score (or = . [ % ic . ; . ] by point, p = . ), arterial lactate (or = . [ . ; . ] by mmol/l, p < . ), total serum bilirubin (or = . [ . ; . ] by umol/l, p < . ), obstruction nonrelated to gallstones (p < . ) and ac complications (liver abcess and/or pancreatitis) (or = . [ . ; . ] p = . ). in addition, time > h between icu admission and biliary drainage was associated to in-hospital mortality (adjusted or = . [ . ; . ] p = . ). conclusion: acute cholangitis is responsible for high mortality in icu. organ failure severity, causes and local complications of cholangitis are predictive factors of mortality as well as delayed biliary drainage. compliance with ethics regulations: yes. the united kingdom) were included (n = ). predictors of one-year mortality were retrospectively screened and tested on a single center training cohort. a predictive score was developed and tested on an independent multicenter cohort. results: four independent pre-transplantation risk factors were associated with one-year mortality after transplantation in the training cohort: age ≥ years (or = . , % ci = . - . , p = . ), pre-transplantation arterial lactate level ≥ mml/l (or = . , % ci = . - . , p = . ), mechanical ventilation with pao / fio ≤ mmhg (or = . , % ci = . - . , p = . ) and pretransplantation leukocyte count ≤ g/l (or = . , % ci = . - . , p = . ). a simplified version of the model was derived by assigning point to each risk factor: the transplantation for aclf- model (tam) score. a cut-off at points distinguished a high-risk group (score > ) from a low-risk group (score ≤ ) with one-year survival of . % vs. . % respectively (p < . ). the model and its simplified version were validated on the independent multicenter cohort. there was a significant difference between the high-risk and low-risk group with one-year survival of % vs. . % respectively (p < . ). conclusion: liver transplantation can be an effective treatment for critically ill cirrhotic patients with hepatic and extra hepatic organ failure provided patients are carefully selected and that they are transplanted at the optimal time in the intensive care. the tam score can help stratify post-transplantation survival and assist clinicians in the transplantation decision-making process at the bedside of aclf- patients. compliance with ethics regulations: yes. rationale: trans-thoracic echocardiography (tte) is commonly used in the initial management of patients with shock in icu. there is little published evidence for any mortality benefit. we compared the effect of echocardiography protocol versus standard care for survival and clinical outcomes. patients and methods: this randomized controlled trial included selected shocked patients (systolic blood pressure < mm hg and signs of organ hypoperfusion) randomized to early tte plus standard care versus standard care without tte. the primary outcome measure was survivalto days. secondary outcome measures included initial treatment and vasopressor weaning. results: consecutive subjects with circulatory shock (low systolic arterial blood pressure (sap) and signs of organ hypoperfusion) at the time of icu admission are included in the study. in the tte group: fluid prescription during the first h was significantly lower rationale: both the negative prognostic value and reversibility of left ventricular (lv) diastolic dysfunction in septic patients remain debated. the excess of mortality in septic shock patients with hyperdynamic profile has only been reported by small-size studies. accordingly, the primary objective of the prodiasys study was to assess the impact of lv diastolic dysfunction (and its severity) and of lv hyperkinesia echocardiographically identified during the initial phase of septic shock on -day survival. the secondary objective was to assess the potential link between lv diastolic dysfunction, cumulative water balance (on day ), and outcome. patients and methods: this was a multicenter, prospective, observational, cohort study. patients older than years hospitalized in icu for septic shock (sepsis- definition) were eligible. exclusion criteria were administration of inotropes, severe left valvular disease, constrictive pericarditis and moribund patients. in each patient, echocardiography was first performed within h after the diagnosis of septic shock and then daily until day , after vasopressor discontinuation, at icu discharge and on day or at hospital discharge, whichever occurred first. vital and biological parameters usually monitored for septic shock management were collected at each echocardiographic assessment. vital status was collected on day . associations between lv diastolic dysfunction or lv hyperkinesia and day- mortality were analyzed using a chi test. adjusted analyses were performed using logistic regression models, including variables known to be linked with the prognosis of septic shock (e.g., severity scores, delay of antibiotherapy). the relationship between the grade (i to iii) of lv diastolic dysfunction and -day survival were analyzed using a logistic regression model. the relationship between the presence of lv diastolic dysfunction and cumulated water balance on day were analyzed using a linear regression model adjusted on the body weight on admission. the relationship between the grade of lv diastolic dysfunction and cumulated water balance on day were analyzed using a linear regression model. diaphragm dysfunction and weaning induced pulmonary edema are two frequent causes of weaning failure but their coexistence and interaction have been poorly investigated. we hypothesized that diaphragm dysfunction may not induce a sufficient decrease in intra-thoracic pressure to increase venous return and generate a weaning induced pulmonary edema. we therefore investigated whether weaning induced pulmonary edema and diaphragm dysfunction are or not associated and evaluated the effect of diaphragm dysfunction on cardiac function and lung aeration during a spontaneous breathing trial (sbt). patients and methods: patients with readiness to wean criteria who had failed a first sbt were eligible. before and after a second sbt, diaphragm function was assessed by measuring the change in tracheal pressure induced by a bilateral phrenic nerve stimulation (ptr, stim), cardiac function (cardiac output, systolic pulmonary arterial pressure) was evaluated with echocardiography and lung aeration was estimated from the lung ultrasound score (lus). plasma protein concentration and hemoglobin were also sampled before and after the sbt. diaphragm dysfunction was defined by ptr, stim < − cmh o and weaning induced pulmonary edema was diagnosed in case of sbt failure associated with ) increase in plasma protein concentration or hemoglobin > % during the spontaneous breathing trial and/or ) early (e) over late peak diastolic velocity ratio > . or e over peak diastolic velocity ratio > . . results: fifty-three patients were included and / ( %) failed the sbt. diaphragm dysfunction was present in / ( %) of patients with weaning induced pulmonary edema, in / ( %) patients with sbt success and in / ( %) patients with other causes of sbt failure (p < . ). during the sbt, diaphragm dysfunction induced a significant increase in systolic pulmonary arterial pressure but no change in cardiac output. patients with diaphragm dysfunction had a higher lus as compared to their counterparts ( ± vs. ± , respectively, p < . ). conclusion: diaphragm dysfunction induces a loss of lung recruitment and a significant increase in systolic pulmonary arterial pressure during the sbt. coexistence of diaphragm dysfunction and weaning induced pulmonary edema is common in case of sbt failure but weaning induced pulmonary edema appears more likely to be involved than diaphragm dysfunction. compliance with ethics regulations: yes. rationale: diaphragmatic weakness in the intensive care unit (icu) is associated with poor outcome. prolonged mechanical ventilation is associated either with a decrease (atrophy) or an increase (supposed injury) in diaphragmatic thickness, both associated with prolonged weaning. shear wave elastography is a non-invasive technique that measures diaphragm shear modulus (sm), a surrogate of its mechanical properties. the aim of this study was to describe the diaphragm shear modulus during the icu stay and to describe its relation with diaphragm thickness. patients and methods: this prospective and monocentric study included all consecutive critically ill patients. ultrasound examination of the diaphragm (aixplorer; supersonic-imagine, aix-en-provence, france) was obtained by two investigatorsevery other day until icu discharge. demographics, diaphragm thickness, sm and outcomes were collected. a mixed model regression was used to study the relation between sm and diaphragm thickness. results: we enrolled patients from december st to june st, being invasively mechanically ventilated during the stay. diaphragm ultrasound evaluation was feasible in / ( %) patients. the duration of mechanical ventilation during the icu stay was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] days with [ ] [ ] [ ] [ ] [ ] days spent on controlled mechanical ventilation. sm was . ± . kpa and diaphragm end-expiratory thickness was . ± . cm upon icu admission. increase and decrease ≥ % during icu stay occured in and percent of the patients respectively for diaphragmatic thickness, and in and percent of the patients respectively for diaphragmatic sm. diaphragm thickness over time was inversely correlated with diaphragm sm and with time spent under mechanical ventilation (table) . diaphragm sm over time was correlated with time spent under pressure support ventilation or under spontaneous breathing (compared to controlled ventilation) and with time spent under deep sedation. diaphragm sm was inversely correlated with age, sepsis, exposition to steroids (table) . no association was found between diaphragm sm and outcomes. discussion: our results are in line with the myotrauma concept, suggesting alteration in diaphragm mechanical properties associated with increased diaphragm thickness in critically ill patients. we hypothesize that this observation most likely reflects muscle injury and tissue infiltration with edema and inflammatory cells. conclusion: shear wave ultrasound elastography suggests that in critically ill patients, the increase in diaphragmatic mass is associated with an alteration in diaphragm mechanical properties as measured by sm. compliance with ethics regulations: yes. rationale: diaphragm dysfunction and intensive care unit (icu) acquired weakness (icu-aw) are associated with poor outcomes in the icu but their long term impact on prognosis and health-related quality of life (hrqol) is poorly established. this study sought to determine whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and icu-aw has a particular impact on two-year survival and hrqol. patients and methods: we used a previous cohort study conducted in our institution to follow up mechanically ventilated patients in whom diaphragm and limb muscle functions were investigated at the time of liberation from mechanical ventilation. diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < cmh o and icu-acquired weakness was defined by medical research council (mrc) score < . hrqol was evaluated with the sf- questionnaire. results: sixty-nine of the patients enrolled in the original study were included in the survival analysis and were interviewed. overall two-year survival was % ( / ): % ( / ) in patients with diaphragm dysfunction, % ( / ) in patients without diaphragm dysfunction, % ( / ) in patients with icu-acquired weakness and % ( / ) in patients without icu-acquired weakness. patients with concomitant diaphragm dysfunction and icu-acquired weakness had a poorer outcome with a -year survival rate of % ( / ) compared to patients without diaphragm function and icu-acquired weakness ( % ( / ) (p < . )). hrqol was not influenced by the presence of icu-acquired weakness, diaphragm dysfunction or their coexistence. conclusion: icu-acquired weakness but not diaphragm dysfunction has a strong negative impact on two-year survival of critically ill patients. the presence of diaphragm dysfunction appears more likely to be a determinant of early prognosis and does not appear to have a significant impact on long-term survival. compliance with ethics regulations: yes. rationale: influenza can lead to severe condition with acute respiratory failure and acute respiratory distress syndrome due to a massive pulmonary inflammatory in response to the viral invasion. lung bacteriobiota has been described to be associated with pulmonary inflammation in chronic respiratory diseases such as chronic obstructive pulmonary disease or cystic fibrosis. lung mycobiota has been poorly investigated despite the well-known role for fungi in numerous respiratory diseases. the aim of our study was to assess the prognostic value of lung bacteriobiota and mycobiota among critically ill influenza patients. patients and methods: we prospectively included influenza patients admitted to icu. sputum were stored a - °c. bacterial and fungal dna were extracted thanks to qiaamp ® powerfecal ® pro dna kit. s rrna gene v -v regions and its regions were amplified by pcr and sequenced on illumina miseq ® . taxonomic assignation was obtained by dada pipeline and microbiota analysis were performed according to day- mortality by the mean of phyloseq package on r . . software. results: thirty-nine patients were admitted to icu for influenza with sputa available and finally dna samples available after extraction. bacteriobiota alpha diversity was significantly lower among non-survivors than survivors when expressed by the mean of shannon index, simpson index or evenness (respectively p = . , p = . , p = . ). area under the curve to predict day- mortality was . , ci [ . ; . ] for shannon index, . ci [ . ; . ] for simpson index and . ci [ . ; . ] for evenness. β-diversity analysis also demonstrated significant differences between survivors and non-survivors (adjusted permutational multivariate anova, p = . ). nonsurvivors had a higher abundance of staphylococcus, haemophilus, streptococcus and moraxella. none of the fungal alpha-diversity index nor beta-diversity were significantively different between survivors and non-survivors. non-survivors had a higher proportion of candida albicans and malassezia but not of aspergillus. conclusion: the lung bacteriobiota profile, but not the mycobiota one, of critically ill influenza patients is associated with day- mortality and may be used to identify subjects with a poor prognosis at the time of admission. compliance with ethics regulations: yes. that takes into account the interaction between multiple cellular pathways. the pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. results: patients ( severe and moderate influenza patients) and healthy control subjects were included in the study. severe influenza was associated with upregulation in several neutrophilrelated pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (net) formation. the degree of upregulation in neutrophil-related pathways was significantly higher in severely infected patients compared to moderately infected patients. severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation, cd + t-cell co-stimulation, cd + t cell and natural killer (nk) cells effector functions. apoptosis pathways were also downregulated in severe influenza patients compared to moderate and healthy controls. conclusion: these findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection. compliance with ethics regulations: yes. rationale: herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ards). however, few is known about herpes simplex virus (hsv) and cytomegalovirus (cmv) reactivation occurring in patients with severe ards under venovenous extracorporeal membrane oxygenation (ecmo). we tried to determine the frequency of herpesviridae reactivation and its impact on patients'prognosis during ecmo for severe ards. patients and methods: we conducted an observational, retrospective study in a medical icu (ards and ecmo referee center) between and . patients with a severe ards requiring a venovenous ecmo for days or more were included. hsv and/or cmv reactivation occurring after ecmo insertion was screened for these patients. patients with immunosuppression, antiviral therapy against hsv and/ or cmv prior to inclusion, or hsv/cmv reactivation known at the time of ecmo insertion were excluded. hsv reactivation was defined by a positive qualitative throat sample (virocult ® ) pcr or positive bronchoalveolar lavage (bal) pcr. cmv reactivation was defined by a positive quantitative blood or bal pcr. results: during a five-year period, non-immunocompromised patients with a severe ards necessitating a veno-venous ecmo were included. sixty-seven ( %) experienced hsv and/or cmv reactivation during ecmo course ( viral co-infection, hsv alone and cmv alone). hsv reactivation occurred earlier than cmv after the beginning of mv ( ( - ) vs. ( - ) days; p < . ) and after ecmo implementation ( ( - ) vs. ( - ) days; p < . ). in univariate analysis, hsv/cmv reactivation was associated with a longer duration of mechanical ventilation ( ( - . ) vs. . ( - ) days; p < . ), a longer duration of . ) vs. ( - ) days;p < . ), and a prolonged vs. ( - ) days; p < . ) and hospital stay ( ( - . ) vs. ( - ) days; p < . ). however, in multivariate analysis, viral reactivation remained associated with prolonged mv only. when comparing patients having cmv (alone or combined with hsv) vs. hsv reactivation alone, cmv positive patients had a longer mechanical ventilation duration and fewer ventilator-free days at day- and a longer icu and hospital length of stay. conclusion: herpesviridae reactivation is frequent among patients with sevre ards under veno-venous ecmo and is associated with a longer duration of mechanical ventilation. cmv seems to have a proper negative role on pulmonary fiunction as compared to hsv alone. hsv and cmv deserve to be researched in severe ards patients under ecmo. compliance with ethics regulations: yes. charlotte vandueren , benjamin zuber , eve garrigues , antoine gros , nicolas epaillard , guillaume voiriot , yacine tandjaoui rationale: respiratory syncytial virus (rsv) is a common cause of pediatric bronchiolitis and influenza-like illness in adults. its involvement in severe infections in adults remains unclear. the captif study aimed at comparing characteristics and prognosis of icu patients infected with rsv and influenza, assuming that, based on the limited evidence, the mortality of rsv infection would be lower than the influenza related one. patients and methods: multicenter franco-belgian retrospective study. adults admitted to icus between /nov/ and / apr/ with respiratory rsv infection were included and matched : to influenza patients on center and icu admission date. patients' characteristics, clinical presentation, and outcome were compared between groups using univariate and multivariable analyses. results: we report here the results for the first cases among included patients. mean age was . ( . ) years and saps- score was ( ), not different between groups. compared to influenza patients, rsv patients more frequently had chronic respiratory failure ( % vs %, p < . ) or immune suppression ( vs %, p = . ). frequencies of cardiac, renal and hepatic chronic diseases were similar. almost all patients had respiratory symptoms (> %), extrarespiratory symptoms were more frequent in influenza patients ( vs %, = . ). rsv patients more frequently had bronchospasm ( vs %, p = . ). clinical presentation such as ards ( %), shock ( %) and pulmonary coinfection ( %) were similar, however sofa score was higher in rsv patients ( . ( . ) vs . ( ), p = . ). the p/f ratio was around mmhg in both groups, paco was higher in rsv patients ( vs mmhg, < . ). respiratory assistance at diagnosis tended to differ (p = . ), rsv patients receiving more non invasive ventilation ( vs %) and less high flow oxygen therapy ( vs %) but invasive ventilation was required similarly ( vs %). during icu stay, ards was more frequent in rsv patients ( vs %, p = . ), accordingly prone position ( . vs . %) and ecmo ( . vs . %) were more frequently needed. length of mechanical ventilation ( days ( - ) ) and icu los ( days ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ) were not different. icu mortality was similar in rsv and influenza patients ( . % and . %), the multivariate analysis did not find an association between type of virus and mortality. conclusion: rsv infection is frequent in adult icu patients. it presents more frequently than influenza as an acute on chronic respiratory failure with bronchospasm. despite difference in case mix and clinical presentation, vrs severity and burden appear similar to influenza justifying effort to prevent and treat it. compliance with ethics regulations: yes. rationale: mortality in acute stroke patients requiring mechanical ventilation ranges from to % at year. studies evaluating indicators of outcome in these patients have limitations, including singlecenter, retrospective designs and no adjustment for withholding/ withdrawal of life-sustaining treatments (wlst). our objective was to identify factors associated with -year survival in acute stroke patients requiring mechanical ventilation. patients and methods: retrospective analysis of a prospective multicenter database between and . icu stroke patients entered in the database and requiring mechanical ventilation within h were included. were excluded patients with stroke of traumatic origin, subdural hematoma or venous cerebral thrombosis. factors associated with -year survival were identified using a cox model stratified on inclusion center, adjusted on wflst occurring during the first h. data are presented as median [q -q ] or percentages. cox model results are presented as hazard ratios (hr) and % confidence intervals (ci). results: we identified patients from icus, aged [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] years and % males. on admission, the glasgow coma score (gcs) was [ ] [ ] [ ] [ ] [ ] [ ] and the saps score was . types of strokes were ischemic ( %), hemorrhagic ( %) and subarachnoid hemorrhage (sah) ( %). ischemic stroke patients received thrombolysis or thromboaspiration in / ( %) cases, and hemorrhagic stroke/ sah patients received neurosurgery or embolization in / ( %) cases. reasons for endotracheal intubation were coma ( %), acute respiratory failure ( %), seizures ( %), cardiac arrest ( %) and elective procedure ( %). sixty-five ( %) patients received a decision of wflst in the first h. one-year survival year was %. variables independently associated with -year survival were stroke type (ischemic as reference, hemorrhagic hr . (fig. ) . inclusion period ( inclusion period ( - inclusion period ( / inclusion period ( - inclusion period ( / inclusion period ( - or having a stroke unit on site was not associated with -year survival. conclusion: in acute stroke patients requiring mechanical ventilation, the reason for intubation and the opportunity to receive a specific stroke therapy are independently associated with long-term survival. these variables should be integrated in the decision process regarding initiation of mv in acute stroke patients. compliance with ethics regulations: yes. rationale: international guidelines recommend targeted temperature management (ttm) between ° and °c for out-of-hospital cardiac arrest (ca) patients. however, it is unknown if this treatment is effective whatever the severity of the insult. we aimed to examine the association between ttm and long-term neurological outcome according to the risk evaluated at time of admission in intensive care unit (icu) using a dedicated and validated score. patients and methods: we used data prospectively collected in the sudden death expert center (sdec) registry (great paris area, france) between may and december and in the resuscitation outcome consortium-continuous chest compression (roc-ccc) between june and may . we used a modified version of the cardiac arrest hospital prognosis (mcahp) score to assess the risk of poor outcome at icu admission in each of datasets. we finally studied the association between ttm use and long-term neurological prognosis according to mcahp score at icu admission divided into tertiles of severity in each of the datasets. results: there were patients analyzed in the french dataset and in the north-american dataset. the mcahp identified categories: low risk (score < points, % of unfavourable outcome), medium risk ( ≤ score < , % of unfavourable outcome) and high-risk group (score > , % of unfavourable outcome). according to the mcahp score at icu admission, ttm was associated with a better long-term neurological prognosis in patients with low risk (aor = . [ . - . rationale: acute ischaemic stroke is associated with a high risk of mortality, morbidity and healthcare-related costs. over the last decades new treatments, such as thrombolysis and thrombectomy, have been introduced. because of their further improvement, complications have been decreasing. this also led to extending indications for treatment to patients who were previously not eligible. the impact of this evolution on long-term outcome and cost-effectiveness has mainly been assessed in clinical trials and simulation studies. patients and methods: this single-centre retrospective study included patients treated for stroke between january and february . functional outcome at days was assessed by the modified rankin scale (mrs). cost data were retrieved from individual invoices of patients. undiscounted total healthcare costs were calculated for the index hospital stay, capped at days. contribution of cost categories to total costs was analysed. mrs at days was used as a proxy for utilities to define quality-adjusted life years (qalys). multivariate analysis was done for gender, age, charlson comorbidity index, pre-stroke mrs, stroke severity (nihss) and treatment modality (thrombectomy, thrombolysis, thrombectomy + thrombolysis, no intervention). incremental cost-effectiveness ratios (icers), associated to each treatment modality, were calculated. results: no intervention was done in patients ( . %). patients ( . %) required thrombolysis, ( . %) thrombectomy and ( . %) the combination. total costs were mean , eur ) . hospitalisation costs (mean , eur, iqr - , ) represented % of total costs, compared with drug costs ( eur, iqr - ), procedural costs ( eur, iqr - ), honoraria ( eur, iqr - ), lab ( eur, iqr - ) and imaging ( eur, iqr - ). mean total costs differed between treatment modalities: , (iqr - , ) eur for no intervention, , ) eur for thrombolysis, , (iqr , ) eur for thrombectomy and , (iqr , ) eur for the combination (p < . ). drivers for total costs were treatment modality (p < . ) and nihss-stroke severity (p < . ). utility scores were . rationale: emergency endotracheal intubation (eti) in the intensive care unit (icu) often concerns hypoxemic patients with hemodynamic instability. a cardiovascular collapse (cvc) after eti is a life-threatening complication. french guidelines suggested systematic fluid loading prior to eti. our study aimed to predict cvc after eti, while using echocardiography, and to evaluate the impact of fluid loading. patients and methods: a prospective study of consecutive intubations was performed from june to november in three icus. patients were selected if mean blood pressure measurements ≥ mmhg before eti. cvc was defined as mean blood pressure < mmhg within min following eti. four echocardiographic examinations were performed: - min before and - min after eti (or when a cvc occurred); -after passive leg raising; - h following eti. patients were classified as fluid responders when the left ventricular outflow tract velocity-time integral increased by at least % compared with baseline. results: echocardiographic examinations were performed. cvc occurred in / procedures ( %). in cvc group, mean dose of diprivan, used for fast sequence induction, was higher ( . ± mg/kg vs . ± . mg/kg, p = . ). in the cvc group, fluid responsiveness was considered in % patients and left ventricular (lv) systolic dysfunction %. lv diastolic dysfunction did not concern any patient in the cvc group. systolic blood pressure (sbp) < mmhg was the sole independent risk factor for cvc occurrence in multivariate analysis: or . ci % . - . , p = . . fluid responsiveness independent risk factors for cvc patients was sbp < mmhg (or . , ci % . rationale: the autonomic nervous system is highly adaptable and allows the organism to maintain its balance when experiencing stress. heart rate variability (hrv) is a mean to evaluate cardiac effects of autonomic nervous system activity and a relation between hrv and outcome has been proposed in various types of patients. we attempted to evaluate the best determinants of such variation in survival prediction using a physiological data-warehousing program (reastoc clinicaltrials identifier nct ). patients and methods: physiological tracings were recorded at hz from the standard monitoring system (intelliview philips mp ) using the synapse software (ltsi inserm umr ), for a h period, during the h following icu admission. all measurements were recorded while patients were laying in bed, with the head at ° and without any medical intervention. physiological data were associated with metadata collection by a dedicated research assistant. hrv was derived using kubios hrv, in either temporal ( (sdnn), (rmssd) and triangular index (ti)), frequency ( (lf), (hf)), non-linear domains (poincaré plotting) and entropy. results: consecutive patients were recorded between may and april . a lower lf/hf (< . ) and sd /sd (< . ) ratios on admission were associated with a higher icu mortality. multivariate analysis enabled to develop a mortality predictive model (bicus) associating spo /fio and hrv parameters (lf/hf and shannon entropy) with an auc = . (p < . ) for a bicus value > (fig. ) . conclusion: hrv measured on admission enables to predict prognosis in the icu, independently of the admission diagnosis, treatment and mv requirements. bicus may help predict prognosis on a real time basis, using parameters derived from standard routine monitoring. compliance with ethics regulations: yes. rationale: stroke, in the context of type diabetes (t d) is associated with a worse outcome than in non-diabetic conditions, reflected by an increased ischemic volume and more intracerebral hemorrhage. an unbalanced diet is one of major risk for developing t d. we aimed at creating a reproducible mouse model of stroke in impaired glucose tolerance condition induced by high fat diet. patients and methods: adult c bl mice ( male and female) were fed for months with either high fat diet (hfd, % lipids, % proteins, % carbohydrates) or a normal diet (nd, . % lipids, . % proteins, . % carbohydrates) . we used a model of middle cerebral artery occlusion (mcao) by a monofilament for min. oral glucose tolerance test and insulin tolerance test were used for evaluating the pre-diabetic state. mice were euthanized h after reperfusion. systemic inflammation, cerebral infarct volume and hemorrhagic transformation were determined. results: hfd was associated with an increased glycaemia following the oral glucose tolerance test. plasma leptinlevels in stroke conditions were significantly higher in hfd vs nd group. the hfd group presented a significant increase of infarct volume (hfd: . ± . mm vs nd: . ± . mm p = . ) and hemorrhagic transformation (hfd: . ± . vs nd: . ± . p = . ) (fig. ) compared to nd group. discussion: in humans, one of the mechanisms leading to insulin resistance is low-grade inflammation. hfd increases gut permeability, which leads microbiota dysbiosis, thereby promoting metabolic endotoxaemia and a low-grade inflammation state. experimental mouse models available for diabetes studies use leptin receptor deficient mice which develop t d or destruction of pancreatic beta cells by streptozotocine injection (t d). studies using diet-induced insulin resistance models generally feed the mice for weeks or more. however, metabolic disorders could appear earlier such as increase inflammatory markers. in our model, a short exposition to hfd ( weeks) leads to an increase of the pro-inflammatory markers as plasma leptin and a more severe stroke status (infarct and hemorrhagic transformation). conclusion: two months of hfd in adult mice altered hyperglycemia control. this metabolic disorder was associated with significantly higher leptin production, increased infarct volume and hemorrhagic complications than in normal-fed mice. this new model is particularly relevant to study stroke under pre-diabetic conditions induced by hfd. compliance with ethics regulations: yes. eight weeks of hfd increase ischemic volume and hemorrhagic transformation. (a)-infarct volume (v) h after reperfusion, all value are mean ± sem, hfd: v = . ± . mm , n = , nd: v = . ± . mm , n = , *p = . (b)-hemorrhage transformation (ht) score h after mcao. all value are mean ± sem hfd: ht score = . ± . , n = , nd: ht score = . +/+ . , n = *p = . rationale: cardiac arrest (ca), as massive ischemia reperfusion (ir), is an universal health issue. medication taken at the time of the ca could have prognosis consequences. no medication has proven its benefit on ca prognosis. pharmacological pre-or postconditioning aims to reduce ir injury but with disappointing results. metformin (met) is a worldwide-prescribed antidiabetic drug, and several clinical reports plead for a potential protective effect in various settings of sterile and non sterile inflammation, including ir. our hypothesis is that met act as a preconditioning drug against ca-induced ir. patients and methods: retrospective single academic medical center survival study (french west indies) on resuscitated ca in icu (institutional ethical committee approval). data were extracted from medical charts, pmsi, and laboratory dbsynergy ™ software. anonymized data were entered on a excel ™ and transferred to ibm ® -spss ® software (v . . . ) for analysis. univariate study (chi- , fisher exact tests, student-t test, mann-whitney u-test if required) was followed by a multivariate model (odd ratio or and % ic: kaplan-meier estimator and non parametric logrank test-mantel cox model). assuming an overall in-hospital mortality for ca in icu of % with an expected mortality decrease of % by met, the number of patients to be included is . results: the inclusion period was to , with included patients ( diabetic patients among whom took met). the d mortality was % in met+ patients (n = ) versus % in nomet patients (n = ), p < . . comparing alive (n = ) versus deceased (n = ) at d in univariate then multivariate analysis, asystole on the first ekg, number of iterative cardiac arrest,sofa, no-flow, lactate, low-flow and sapsii appear as independent criteria associated with d mortality.conversely, met intake showed up as a protective criterion (or . , ci . - . ). the survival curve, including strata of low-flow duration at the cut-off min, is reported on the fig. . among diabetic patients (n = ), the mortality of patients in the met+ (n = ) was % versus % in the nomet (n = ), p = . . conclusion: in diabetic patients suffering of massive ir related to resuscitated ca, a current treatment by met is associated with a better survival. these results support a protective effect of met and are important to initiate prospective evaluations, because of millions diabetic people around the world and the potential benefit of met. the potential benefit in non diabetic patients and in sterile as well as non sterile inflammation should be addressed. compliance with ethics regulations: yes. rationale: during systemic inflammation, the accumulation of misfolded proteins in the endoplasmic reticulum (er) induces er stress (ers). in animal models, the inhibition of ers reduces inflammatory response and organ failure. cardiopulmonary bypass (cpb) induces a significant systemic inflammatory response but ers expression has never been described in cardiac surgery patients. our objective was to describe the variations of the glucose related protein of kda (grp ), the final effector of the ers, during cpb. patients and methods: we conducted a prospective monocenter study including patients undergoing cardiac surgery with cpb. two samples (paxgene ® tube + edta tube) were taken at three times: before cpb, h after the end of cpb (h -cpb) and h after (h -cpb). after rna isolation and reverse transcription, we performed a quantitative polymerase chain reaction to evaluate the expression of gene encoding for grp and determined the plasma level of grp using enzyme-linked immunosorbent assay. our main objective was to study the variation of grp between pre-cpb and h -cpb samples. our secondary objectives were to evaluate the association of ers with morbi-mortality: organ failure at h (catecholamines and/or invasive ventilation and/or acute renal failure), troponinemia and pao /fio ratio (lung damage control). fig. ). we found an inverse correlation between grp plasma level and troponinemia at h (r = − . ; % ci[− . ; − . ]; p = . ) and a correlation between the pao /fio ratio and grp plasma level at h (r = . ; % ci[ . ; . ]; p = . ). we showed a significant relationship between the variation in plasma concentration of grp and post-operative organ failure after cpb. further studies are needed to better understand the molecular mechanisms of ers in acute inflammatory organ failure in humans. compliance with ethics regulations: yes. patients and methods: in a retrospective monocentric study ( / - / ) conducted in cardio-vascular surgical intensive care unit (icu) in henri mondor teaching hospital, all consecutive adult patients who underwent peripheral va-ecmo were included, with exclusion of those dying in the first h. diagnosis of acute mesenteric ischemia was performed using digestive endoscopy, abdominal ct-scan or fist-line laparotomy. significative results in the univariate analysis were analyzed in a multivariate analysis using logistic regression. results: va-ecmo were implanted. median age was ( - ) years and median . va-ecmo was implanted after a cardiotomy in % of the cases and for a medical reason in % of the cases including % of refractory cardiac arrest. patients characteristics are reported in the table. acute mesenteric ischemia was suspected in patients, with a delay of ( - ) days after ecmo implantation. digestive endoscopy was performed in patients, ctscan in five patients and first-line laparotomy in three patients. acute mesenteric ischemia was confirmed in patients, i.e. an incidence of %. laparotomy was performed in six of the patients, two having a stage i colitis ischemitis with stable conditions and being considered too severe to undergo futile surgery. overall mortality was %. all the patients with acute mesenteric ischemia died in the icu. independent risk factors of developing acute mesenteric ischemia were renal replacement therapy , p = . )) and onset of a second shock state within the first days of icu stay (or . ( % ic . - . , p = . )). conversely, early enteral nutrition was negatively associated with acute mesenteric ischemia (or . ( % ic . - . ), p . ). conclusion: acute mesenteric ischemia is a relatively frequent condition among patients under va-ecmo for cardiogenic shock. its extremely poor prognosis requires low threshold of suspicion. compliance with ethics regulations: yes. ( ). it allows the computation of trans-pulmonary pressure ( ) and can be used to set positive end-expiratory pressure (peep) ( . ) . prone position(pp) can reduce mortality in patients with acute respiratory distress syndrome (ards), but peep selection in pp is controversial. in human ards end-expiratory pes at zero flow (peept,es) was not different between supine (sp) and pp at same peep ( ). as no study measured ppl in sp and pp in ards we aimed at comparing peept,es and end-expiratory ppl at zero flow (peept,ppl) in this condition. our hypothesis was that peept,es was close to dorsal peept,ppl (peept,ppldorsal) in sp and to ventral peept,ppl (peept,pplventral) in pp. in eight female pigs of kgs intubated, sedated, paralyzed and mechanically ventilated, ards was induced by repeated saline lavage until pao /fio < mmhg under fio and peep cmh o. pes was measured by nutrivent catheter. ppl was measured by custom-made pouch sensors inserted surgically into the right anterior and posterior sixth intercostal space. ppl sensors were filled with air. after ards induction animals were randomly assigned to sp or pp. in each position, a recruitment manoeuver was performed and peep decreased from to cmh o by steps of cmh o lasting min each, then the animals were crossed over into the alternate position where the same procedure was done. at the end of each step nonstressed volume and correct position (baydur maneuver) were determined for pes and ppl sensors, then a -s end-expiratory occlusion was performed and pes and ppl recorded. linear mixed model was used to compare the value of pes and ppl at each peep and position. results: box-and-whisker plots of pes and ppl in sp and pp are shown in fig. . there is marked dorsal-to-ventral gradient in ppl at each peep in sp, which is reverted in pp at peep and only. there was no interaction between pressures and peep or position. with increasing peep pes increased significantly from peep in sp and pp. peept,pplventral was significantly lower than peept,es in sp but not in pp. (medtronic) , carescape (ge)) were set in pressure support cmh o, peep cmh o, fio % and equipped with the same double limb ventilator circuit (intersurgical) without any humidification device. asl bench model was set with inspiratory/expiratory resistance (r) and compliance (c) combinations: r / -c , r / -c and r / -c mimicking normal, ards and copd conditions, respectively ( ) . inspiratory effort generated by asl consisted of consecutive breaths obtained from the esophageal pressure in a real patient at the time of a spontaneous breathing trial. for each icu ventilator and rc combination, two steps were performed: in the first, atc was not activated and ventilator attached to asl without ett (atc-ett-); in the second, atc was set on at % compensation for an ett mm id and such an ett (shiley hi contour, covidien) joined icu ventilator to asl (atc+ ett+). the null hypothesis is that vtatc+ ett+ minus vtatc-ett-is . primary end point was the breath by breath paired difference betwen atc+ ett+ and atc-ett-. it was tested to zero for each ventilator in each rc condition. results: median vt was ml. table displays mean (± sd) difference in vt (ml) between atc+ ett+ and atc-ett-: a negative value means that atc under delivers and a positive value that atc over delivers vt for a given patient's inspiratory effort and rc. in four ventilators (c , s , elisa and ) atc almost systematically under delivered vt. in several instances under compensation was greater than % median vt. by contrast atc performed better with the other three ventilators (evita xl, v and carescape ). conclusion: atc tended to under deliver vt. furthermore, there were marked differences between icu ventilators the clinician should be aware of when using the atc option. compliance with ethics regulations: na. rationale: during the last decades, identification of factors associated with ventilation-induced lung injury has led to improved survival in patients with ards. the mechanical power of ventilation is the total energy transmitted from the ventilator to the respiratory system per unit of time and comprises three different components: elastic related to peep, elastic related to tidal volume and resistive. this integrative variable has been recently proposed as an useful predictor of ventilationinduced lung injury and death among ventilated patients. our goal was to determine the respective impact of the total mechanical power and its three components on the outcome of patients with ards. patients and methods: we performed a post hoc analysis of a randomized, controlled study of patients with ards with a pao /fio ratio < . themechanical power at inclusion and averaged on the first days after inclusion (total and its three different components) was computed according to the following equation: powerrs (j/ min) = . respiratory rate tidal volume [peep ( ) + ½ driving pressure ( ) + (peak pressure-plateau pressure) ( )], where the ( ), ( ) and ( ) parts correspond respectively to the elastic related to peep, elastic related to tidal volume and resistive components. the association between each of these four types of mechanical power evaluated during the first days after inclusion and mortality at d was assessed one after the other through multiple logistic regression, allowing control for potential confounding variables at inclusion (age, igs score without age, group of randomization, pao /fio , arterial ph). results: data from patients were analyzed, among which ( . %) died before d . there was no difference concerning the mechanical power at inclusion between survivors and non survivors (either total or its three components). among the four different types of mechanical power tested during the first days after inclusion, the elastic component related to tidal volume was the only one that was independently associated with mortality at d (or . ; % ci . - . ; p = . ) (figure) . conclusion: our study shows that only the elastic component of the mechanical power related to tidal volume independently predicted mortality at d among patients with ards, whereas the total mechanical power, its elastic component related to peep and its resistive component did not. further studies are needed to better define how the mechanical power of ventilation could be useful to synthetize the risk of ventilation-induced lung injury. compliance with ethics regulations: yes. probability of death at d as a factor of mean value (on d -d ) of the elastic component related to tidal volume of the mechanical power. to examine the effect of early-stage mechanical ventilation (mv) on diaphragmatic contractility. in the nd step, if a diaphragmatic dysfunction was detected, we assessed its influence on the weaning from ventilator. patients and methods: we measured prospectively the ultrasounddiaphragmatic thickening fraction (dtf) between groups: a study group versus a control group (n = for each). the study group included all adult patients receiving mv, in whom, the dtf was measured within a minimum of h and a maximum of days of mv. for the control group, were enrolled after their approval for participation, adult volunteers in spontaneous ventilation (sv). patients with factors affecting the diaphragmatic contractility (neuromuscular disease, severe obesity, and neuromuscular blockers…) were excluded. the ultrasound measurements were obtained at the zone of apposition of the right hemithorax. teleinspiratory and telexpiratory diameters (tid/ ted) were taken on the medio-axillary lines: posterior, median and anterior. the dtf was calculated as following: dtf = (tid-ted/ted) x . at the st step, the dtfs were compared and at the nd step: the relationship between dtf and weaning was analysed. results: our groups were comparable in corpulence and co morbidities. the sv group was younger ( vs. years, p < . ) with a predominant female composition. the diaphragmatic exploration concluded that in the mv group, the mean tid tended to be higher but without significant difference ( . + versus . + mm, p = . ), the mean ted was significantly higher ( . + versus . + . mm, p = . ) and dtf was significantly lower ( . + . % versus + . %, p = . ). the ventilation mode had no effect on dtf ( . + % for control volume vs. . + % for psv mode, p = . ). fourteen among ventilated patients had a successful weaning with a mean duration of days. a negative correlation was found close to significance between dtf and weaning duration (rho = − . and p = . ). a dtf value > % wasassociated with weaning success (or = , % ci = [ . - . ] and p = . ) with sensitivity = . %, specificity = %, ppv = % and npv = %. conclusion: the diaphragmatic contractile function was altered from the first days of mv. weaning duration seemed to be negatively correlated with dtf, and a dtf at the first days of mv greater than % was predictive of weaning success. compliance with ethics regulations: yes. rationale: mechanical ventilation is a life-saving treatment that is however associated with lung injury and/or diaphragm dysfunction. the optimal ventilator settings to provide lung protective ventilation while maintaining safe diaphragm activity are difficult to determine. a noninvasive and bedside evaluation of the diaphragm activity could be helpful in this context. the present study investigated whether changes in diaphragm shear modulus (i.e. stiffness, Δsmdi) assessed by ultrasound shear wave elastography (swe) may be used as a surrogate of changes in transdiaphragmatic pressure (Δpdi) in mechanically ventilated patients. patients and methods: patients had to be ventilated for at least h without contraindications for the placement of an oeso-gastric catheter. pdi was monitored continuously and smdi was measured at the zone of apposition of the right hemi-diaphragm, at hz sampling rate. measurements were performed twice under initial ventilator settings and at the end of a weaning trial. pearson correlation coefficients (r) were computed to determine within-individual correlations between pdi and smdi and changes in pdi and in smdi occurring between initial ventilator settings and the end of the sbt were compared by a paired test. results: twenty-five patients were enrolled and displayed a significant correlation between Δsmdi and Δpdi (mean r = . , range = . - . , all p < . ) (fig. a ). compared to their counterparts, patients with significant within correlations had a lower respiratory rate ( . ± . vs . ± . breath/min. respectively; p < . ) and a significant increase in Δsmdi ( . ± . kpa vs . ± . kpa. p < . ) between initial ventilator settings and the sbt. patients without Δsmdi-Δpdi correlation only displayed an increase in Δpdi ( . ± . vs . ± . cmh o, p < . ) at the end of the sbt with no concomitant significant increase in Δsmdi ( . ± . kpa vs . ± . kpa, p > . ). (fig. b) . conclusion: smdi obtained by swe appears as a promising technique to assess diaphragm activity in mechanically ventilated patients but technological improvements are necessary to increase swe sampling rate before enabling its generalization in the icu. compliance with ethics regulations: yes. rationale: end-inspiratory (eip) and end-expiratory (eep) pauses are commonly used during volume assist control ventilation to assess plateau pressure and total positive end-expiratory pressure (peeptot). they can also be used during assisted ventilation (av) for muscle pressure assessment. it requires ventilators able to perform eip during av. plateau pressure (pplat) usually increases in av during eip due to "hidden" inspiratory effort. pressure muscular index (pmi) is equal to pplat minus the sum of peeptot (measured during an eep) and set pressure support (ps); it theoretically reflects patient's effort without esophageal pressure (pes) monitoring. pes is the gold standard method to assess inspiratory muscle pressure (pmus, difference of pes drop at neural end-inspiration and correction factor for chest wall elastance and tidal volume). we aimed to illustrate the feasibility of measuring pmi using a standard icu ventilator at the bedside and study the correlation between pmus and pmi. patients and methods: measurements were recorded in icu patients. pes was measured using an nasogastric probe (equipped with an esophageal balloon) inserted for advanced monitoring (severe acute respiratory distress syndrome-ards) or for a study protocol (difficult weaning after copd exacerbation). recorded eip, eep and pes were used for post hoc analyses. results reported as ranges and median [iqr] . correlation between pmus and pmi tested with spearman correlation test. results: out of eip and eep duos could be analyzed ( -esophageal spasm/ -calibration error). ventilator mode was pressure support ventilation (ps - cmh o). cmh o, pmus = . [ . - . ] cmh o, pmi = . [ . - . ]. for all recordings, spearman r coefficient between pmus and pmi was . (p = . ). conclusion: muscular effort can be assessed in av using eip and eep using icu ventilators. however, recordings can be influenced by expiratory muscles contraction. patient's ability to follow directions during the maneuvers is an important factor to obtain reliable values. there seem to be a correlation in our small sample between muscular pressure assessed without and with pes. compliance with ethics regulations: yes. rationale: severe pneumonia can culminate in acute respiratory distress syndrome (ards). an uncontrolled inflammatory response is a key feature favoring transition towards ards. however, the underlying mechanisms remain poorly understood. in this context, the contribution of "innate t cells" (itc) -a family of non-peptide reactive t cells comprising nkt cells, mucosal associated invariant t (mait) cells and γδt cells-has never been explored. itc have emerged as key players in orchestration of the host response during infections and inflammation processes. for these reasons, these cells are already seen as potential therapeutic targets in other medical fields (especially oncology). here, we hypothesized that a tight regulation of their functions could be paramount to control the inflammatory response and to prevent ards development. patients and methods: to explore this, we combined a murinemodel of influenza a virus (iav) infection mimicking ardssymptoms and a clinical study recruiting patients admitted in icu for severe pneumonia. using flow-cytometry approaches, we investigated ( ) the abundance and dynamics of itc in various compartments, ( ) their pattern of activation/regulation markers (respectively cd and pd- ) and ( ) their cytokine production. results: during experimental iav pneumonia, itc were transiently recruited into the airways. unlike γδt and nkt, mait cells phenotype was largely changed, displaying a progressive cd overexpression and increased il- a production. during the resolution phase, up to % of pulmonary maits expressed pd- (versus < % in controls), which can suggest emergence of regulatory functions. last, using gene-targeted mice, we suggested that mait cells confer a protective effect during pneumonia. in the ongoing clinical study, the proportion of circulating mait cells in patients was markedly decreased compared to controls ( . ± . % versus . ± . % of t cells), but not for nkt or γδt cells. notably, some patients with severe ards presented detectable levels of maits in their respiratory fluids. in addition, circulating mait cells in patients overexpressed cd and pd- ( . % and % respectively), but with a reduced proportion able to produce il- and ifnγ, compared to healthy controls. lastly, proportion of activated (cd +) mait cells significantly decreased with clinical improvement. conclusion: this translational approach combining in vivo animal experiments and clinical samples with ex vivo experiments indicates a preferential modulation in mait cells functions during severe pneumonia. these data justify an in-depth analysis of mait cells activation mechanisms and functions in this context, in order to further explore a potential use as a disease-progression marker and -in a long term perspective-as a potential therapeutic target. compliance with ethics regulations: yes. representative flow-cytometry dot-plots of mait cells labelling using fluorophore-conjugated mr tetramers loaded with -op-ru from lungs of an infected mouse (a) and blood sample of a patient with pneumonia (b). c: frequency of mait cells, proportion of cd and pd- + mait cells in bronchoalveolar lavage during experimental murine pneumonia. d: blood frequency of mait cells in patients with pneumonia compared with healthy controls (as % of total t cells) rationale: immune paralysis following hyperinflammatory states increases the risk of secondary infections and death. reversing t-cells exhaustion using recombinant il or immune checkpoints inhibitors may improve the prognosis of patients with sepsis admitted to the icu. however, there is an unmet need to better characterize the state of t-cells exhaustion in these patients, its reproducibility and its correlation with the outcomes before implementing immunotherapy in the therapeutic armamentarium against sepsis. patients and methods: prospective observational cohort study performed in two tertiary-care icus in a university hospital. peripheral blood mononuclear cells were collected at day in adult patients with sepsis admitted to the icu. the level of cd + and cd + t-cells exhaustion was quantified using multi-color flux cytometry targeting the following exhaustion markers: pd- , b and cd . cd + regulatory t-cells (cd + cd + cd hi cd lo cells) were also assessed. results: the patients included in the study could be split in five clusters according to their dominant pattern of exhaustion markers on cd + t-cell (i.e. no markers, pd- +, b +, b + cd + and b + pd- +) and independently of their underlying morbidities. no patients harbored a fully exhausted triple-positive pattern. by multivariate analysis, saps gravity score at day (p = . ), a dominant b and/or pd- cd + pattern (p = . ) and lung sepsis (p = . ) where associated with the risk of death at day , whereas hemoglobin level was associated with survival (p = . ). no cd + or cd + exhaustion pattern independently predicted the risk of secondary infections. neither the level of cd + regulatory t-cells nor the dominant cd + exhaustion pattern was associated with the outcomes. rationale: there is growing use of multiplex polymerase chain reaction (mpcr) for respiratory virus testing in patients with communityacquired pneumonia (cap). data on one-year outcomes in patients with severe cap of bacterial, viral and unidentified etiology are scarce. patients and methods: a single-center retrospective study was performed in intensive care unit (icu) patients with known one-year survival status who had undergone respiratory virus testing for cap by mpcr. one year after icu admission, mortality rates and functional status were compared in patients with cap of bacterial, viral or unidentified etiology. results: there were ( . %) patients in the bacterial group, ( . %) in the viral group and ( . %) with unidentified etiology. one-year mortality was . % (n = / ), % (n = / ) and . % (n = / ), respectively (p = . ). in multivariate analysis, one-year mortality was higher in the bacterial group than in the viral group (hr . , % ic . - . , p = . ), had a trend to be higher in the bacterial group compared to the unidentified etiology group (hr . , % ic . - . , p = . ) and was not different between the viral and unidentified etiology groups (hr . , % ic . - . , p = . ). severe dyspnea (mmrc score = or death), major adverse respiratory events (new homecare ventilatory support or death) and severe autonomy deficiencies (adl katz score ≤ ordeath) were observed in / ( . %), / ( . %) and / ( . %) patients, respectively, with no difference between groups. conclusion: cap of bacterial origin was associated with a poorer prognosis than viral or unidentified etiology. impaired functional status was observed in a substantial proportion at one-year, irrespective of the causative microorganisms involved. compliance with ethics regulations: yes. interest of unyvero multiplex pcr (curetis) for bal rapid microbiologic and antibiotic susceptibility documentations in immunocompromised patients under antibiotic therapy jean-luc baudel , jacques tankovic , redouane dahoumane , salah gallah , laurent benzerara , jean-remy lavillegrand , razach abdallah , geoffroy hariri , naike bige , hafid ait-oufella , nicolas veziris , eric maury , bertrand guidet rationale: our aim was to evaluate the interest of the unyvero rapid ( . h) multiplex pcr assay (performed on bronchoalveolar lavage [bal] samples) for the management of immunocompromised patients already treated with antibiotics and diagnosed with pneumonia (according to clinical and radiological findings). we thus performed an observational study that compared the results (and the length of time to obtain them) of routine microbiological evaluation and unyvero assay. patients and methods: from july to january and from april to august , we examined bal samples from immunocompromised patients (coming from hematology, oncology, hepatology, gastroenterology, internal medicine, and neurology units) diagnosed with pneumonia (based on clinical and radiological findings), and already receiving antibiotic treatment. the following data were collected: age, gender, saps score, lung ct scan ( %) or x-ray ( %) results, duration and content of prior antibiotic therapy, direct examination, culture, antibiogram and unyvero results, secondary confirmation of pneumonia or not, possible changes in antibiotic therapy that could have been made after obtention of unyvero results. informed consent was obtained from all patients. results: bal samples were analyzed in immunocompromised patients (m/f ratio . , saps . ± . ) mostly with hematologic ( %) or oncologic ( %) diseases. the patients received either corticosteroids ( %), or chemotherapy ( %), or immunotherapy ( %). % of the patients were under mechanical ventilation, % under optiflow. % presented a shock, % had aplasia or neutropenia, % were allografted, % were autografted. the duration of prior antibiotic therapy at the time of bal were . ± . days. direct examination was positive in . % of the cases, culture (both above and under the classical threshold of cfu/ml) in %, unyvero in . %. a retrospective analysis of all the cases confirmed the initial diagnosis of pneumonia in only % of the cases. compared to culture, the sensitivity of unyvero was %, its specificity %. unyvero could permit to rapidly deescalate antibiotic therapy in % of the cases and to rapidly stop it in %. the unyvero assay on bal samples is useful in this specific population for rapid obtention of microbiological results and also for confirmation of the negativity of cultures and thus permits a better management of antibiotic therapy, leading to a reduction of antibiotic resistance selection pressure in the icu. compliance with ethics regulations: yes. do not underestimate rsv pneumonia among critically ill patients erwan begot , suzanne champion , charline sazio , benjamin clouzeau , alexandre boyer , hoang-nam bui , marie-edith lafon , camille ciccone , julia dina , didier gruson , renaud prével chu bordeaux, medical intensive care unit, bordeaux, france; chu bordeaux, virology laboratory, bordeaux, france; national reference center for measles mumps and rubella, chu de caen, caen, france correspondence: erwan begot (erwan.begot@chu-bordeaux.fr) ann. intensive care , (suppl ):f- rationale: respiratory syncitial virus (rsv) is a well-known cause of respiratory failure among neonates but its pathogenicity in adults is now emerging as a potential cause of viral pneumonia. data are limited with conflicting results regarding rsv pneumonia severity in adults. data are lacking about critically ill rsv patients' characteristics and outcomes. the aim of this study is to compare rsv patients' characteristics, care and outcomes to influenza patients' ones. patients and methods: patients diagnosed with rsv and influenza pneumonia admitted to our medical icu were included. data were retrospectively recorded. quantitative data are expressed by median and interquartile range and compared by use of mann-whitney test. qualitative data are expressed by number and percentages and compared by use of fischer exact t-test. rsv strains were prospectively collected. results: eighteen critically ill patients with rsv pneumonia and with influenza pneumonia were included. rsv and influenza patients had the same characteristics at admission except for age (respectively yo [ ; ] and acute respiratory distress syndrome rates (respectively / ( %) vs / ( %), p = . ). they received similar treatment as suggested by oro-tracheal intubation rates (respectively / ( %) vs / ( %), p: . ) and antibiotics prescription (respectively / ( %) vs / ( %), p: . ). rsv and influenza patients also had the same rates of bacterial co-infections ( / ( %) vs ( %), p: . ). invasive aspergillosis remained a rare event but also occurred among rsv patients ( / ( %) vs / ( %), p: . ). acute coronary syndromes were as frequent in both groups (respectively / ( %) vs / ( %), p = . ). day- mortality was similar between rsv and influenza patients (respectively / ( %) rationale: respiratory distress from seawater drowning is commonly considered multifactorial. etiologies are debatable and include heart failure, infection and acute respiratory distress syndrome (ards). documented bacterial infections seems mostly related to the site of drowning. data in this regard are scarce with prospective studies lacking. the objective of our study was to describe prospectively the characteristics and determinants of respiratory distress from seawater drowning. patients and methods: all patients admitted for seawater drowning to seven intensive care units (icu) on the french riviera in the summers of and were prospectively included. recorded data included clinical features on examination, personal history, chest x-rays, echocardiography and biological results obtained within the first h. a paired student's t-test was used to study statistical differences between quantitative variables on admission and during early evaluation (i.e. first h). results: forty-eight patients were admitted to seven centers of which ( %) were diagnosed as having ards, ( %) early pneumonia and ( %) acute cardiogenic pulmonary edema. twenty-one ( %) respiratory samples were collected but bacterial culture was positive in only cases. multidrug-resistant bacteria were not observed, and amoxicillin-clavulanate as first-line treatment was effective in all cases. echocardiography performed in ( %) patients was normal and unable to identify specific patient profiles. the median clinical pulmonary infection score (cpis) on admission was (iqr, - ) and decreased rapidly and significantly (p < . ) within h to (iqr, - ) (fig. ) . conclusion: data from this multicenter cohort suggest that respiratory distress following seawater drowning can mimic bacterial pneumonia during the first h with subsequent rapid clinical improvement in patients admitted to the icu. probabilistic antibacterial therapy should therefore be limited to the most severe patients. isolate ards is often the only etiology found and is resolutive within h. this prospective cohort is the largest of its kind and gives a better insight into the limited impact of cardiogenic and infectious processes on sea drowning-related respiratory distress. compliance with ethics regulations: yes. rationale: patients treated with "extracorporeal membrane oxygenation" (ecmo) are at a higher risk of developing nosocomial infections and they are consequently often treated with beta-lactams. french guidelines recommend obtaining beta-lactam trough concentrations above four times the minimal inhibitory concentration (mic) of the causative bacteria. the ecmo device may alter the pharmacokinetics of these medications, which may result in underexposure to beta-lactam antibiotics. patients and methods: this observational, prospective, multicenter, case-control study was performed in the intensive care units of two tertiary care hospitals in france. ecmo patients with sepsis treated with piperacillin-tazobactam were enrolled. control patients were matched according to sofa score and creatinine clearance. the pharmacokinetics of piperacillin was described based on a population pharmacokinetic model, allowing to calculate the time spent above × the mic breakpoint for pseudomonas aeruginosa susceptibility after the first dose and at steady state between two piperacillin infusions. results: forty-two patients were included. the median age was years [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , the sofa score was [ ] [ ] [ ] [ ] [ ] [ ] , and median creatinine clearance was ml/min . there was no significant difference in the time above x mic in patients treated with ecmo and controls during the first administration (p = . ) and at steady state (p = . ). there was no significant difference between the trough at steady state (p = . ), with / patients ( %) exhibiting concentrations of piperacillin lower than x mic. ecmo support was not associated with a steady state trough concentration below x mic (or = . [ . - . ], p = . ). the only variable independently associated with this risk was a creatinine clearance ≥ ml/min, (or = . [ . - . ], p = . ). conclusion: ecmo support has no significant impact on piperacillin exposure. intensive care unit patients with sepsis are, however, frequently underexposed with piperacillin, which suggest that therapeutic drug monitoring should be strongly recommended for severe infections. impact of a visual support dedicated to prognosis of patients on symptoms of stress of family members rationale: family members commonly have inaccurate expectations of patient's prognosis. adding to classic oral information a visual support, depicting day by day the evolution of the condition of the patient, improves the concordance in prognosis estimate between physicians and family members. the objective of this study was to evaluate the impact of this support on symptoms of anxiety/depression of family members. patients and methods: we conducted a bi-center prospective beforeafter study. all consecutive patients admitted in the two icus were eligible. in the before period ( months), family members received classic oral information. in the after period ( months) , in addition to classic oral information, the visual support ( fig. ) was available for family members in the patient's room from the day of admission until discharge from the icu. at day and from admission, symptoms of anxiety/depression of referent family member were evaluated by hospital anxiety and depression scale (hads). results: patients and their referent family members were included ( in period before and after). characteristics of patients of the two groups were similar regarding age, reason for admission, saps ii at admission and sofa score at day . also characteristics of referent family members were comparable in terms of age, sex ratio, type of relationship with the patient and number of visits since admission. at day , total had score was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the group before without the support and [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the group after with the support (p = . ). the prevalence of symptoms of anxiety (had-a score > ) and depression (had-d score > ) was similar in the two groups (respectively . % and . % in the group before, and . % and . % in the group after (ns)). at day , total had score was in the group before [ - ] and [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the group after (p = . ). by multivariate analysis the following factors were significantly associated with total had score > at day : age of patient ]), number of visits of referent ) and previous or current treatment of referent for anxiety or depression . ]). conclusion: in this study, the use of a visual support dedicated to prognosis of patients did not modify the level of stress of family members. compliance with ethics regulations: yes. rationale: the use of sedation and opioids at the end of life is a topic of considerable ethical debate. incidence of discomfort during the end-of-life of icu patients and impact of sedation on discomfort are poorly known. patients and methods: post-hoc analysis of an observational prospective multicenter study comparing terminal weaning vs. immediate extubation for end-of-life in icu patients, aimed at assessing the incidence of discomfort events according to levels of sedation. discomforts including gasps, significant bronchial obstruction or high behavioral pain scale score, were prospectively assessed by nurses from mechanical ventilation withdrawal until death. level of sedation was assessed using the richmond agitation sedation scale (rass). results: among the patients included in the original study, ( %) experienced discomfort after mechanical ventilation withdrawal. patients with discomfort received lower doses of midazolam and equivalent morphine, and less frequently had deep sedation (rass - ) than patients without discomfort ( % vs %, p < . ). after multivariate logistic regression, immediate extubation was the only factor associated with discomfort whereas deep sedation and administrations of vasoactive drugs were two factors independently associated with no discomfort. death occurred less rapidly in patient with discomfort than in those without discomfort ( . h [ . - . ] vs . [ . - . ], p < . ) (figure) . long-term evaluation of psychological disorders in family members of dead patients did not differ between those with discomfort and the others. discussion: despite the theoretically expected anticipatory titrated doses of opioids and benzodiazepines to alleviate any discomfort after withdrawal of mechanical ventilation, half of the patients did not receive sedation or opiate when the decision to withdraw mechanical ventilation was taken. a major point that could interfere with the continuous deep sedation practice until death is the fear of potentially hastening death, and there is much controversy regarding its proper use in end-of-life care. conclusion: discomfort was frequent during end-of-life of icu patients and was mainly associated with terminal extubation and less profound sedation. compliance with ethics regulations: yes. rationale: bereavement in intensive care unit (icu) is associated with psychiatric disorders on relatives called post-intensive care syndrome family (pics-f). no isolated intervention (such as condolence letter) has shown a positive effect on these disorders, despite a well acceptance by relatives. we thought that a more integrated bereavement program should be considered. the goal of this study is to evaluate a combined psychologist-physician post-death meeting (pdm) in a bereavement program to evaluate needs and adhesion of relatives, and the effect on symptoms of anxiety and depression. patients and methods: monocentric, prospective study focused on relatives of patient admitted > h and deceased in icu. during patient's stay, relatives' presence was allowed on a h-basis and they could meet a clinician psychologist. formal meeting between relatives and the staff was realized at patient's admission and after important decision-making treatment. two weeks after patient's death, the psychologist called relatives to offer emotional support and to invite to a pdm. pdm occurs weeks after patient's death with the psychologist and the physician in charge of the patient. the objectives of the meeting were to provide emotional support, to answer medical question, and to detect symptoms of anxiety and/or depression with the hospital anxiety and depression scale (hads). we hypothesized that pmd would be able to alleviate pics-f at months. we aimed to enroll families to detect a % lowering of hads. results: the rate of pdm acceptance was lower than expected. after inclusions, only relatives accepted the pdm, whereas the phone call was well perceived ( %). main association with acceptance of pmd was a short duration of icu stay ( . days [ - . ] vs . days [ . - . ] p = . ) and icu admission for acute respiratory failure ( . % vs . %, p = . ) ( table ) . we found no relation between the number of in icu meeting (psychologist of medical staff) and pmd acceptance. for relatives who accept pmd we found a high proportion of symptoms of anxiety and depression ( % and %) with a hads at . [ - . ] (median, iqr). no evaluation was performed at months. conclusion: post death contact appears well perceived by relatives but pmd quite useless. this result may be explained by the inclusion of only late death (> h) where psychologist and medical staff had the opportunity to support relatives. further study should focus on early death (< h). compliance with ethics regulations: yes. rationale: pediatric intensivists frequently question themselves on the issue of limitation or termination of life-sustaining treatments (llst) carried out on children. such a decision comes under the claeys-leonetti law which forbids doctors from applying unreasonable treatment however, every so often, parents oppose themselves to a collegial llst decision that the medical and paramedical team had taken. such cases can even end up in court. in order to sort out this problem, this study focused on the factors that underlie the disagreement and the solution brought forward by pediatricians whenever parents demand to persue treatments although considered as unreasonable obstinacy. patients and methods: we carried out a qualitative study involving three multipurpose pediatric critical care unit. all pediatricians operating within these units were contacted. those who volonteered were met individually for a semi-directed interview. every interview was recorded and entitled to a complete hand-written retranscription. the interviews were analysed following the phenomenological interpretive analysis method and were subject to dual listing. results: pediatricians out of took part in the study. / claimed they would increase treatments or carry out cardiopulmonary resuscitation acts if asked to do so by parents, even if this went against the initial collegial decision. / claimed they would persue treatments although not beyond the current level. / said they would oppose themselves to parents concerning blood transfusion for comfort reasons. several key factors were identified as leading a doctor to the non-application of a llst decision: the certainty regarding the child's death on a short or mid-term basis ( / ), the litigiousness risk ( / ), the apprehension of mediatic pressure ( / ), the fear of a violent reaction from parents ( / ), other self-interest positions within the medical team ( / ), empathy towards parents ( / ), the uncertainty concerning the neurological prognosis ( / ), the lapse of time needed to fully accept the application in force of a decision ( / ). pediatricians out of admitted their own-suffering when confronted to the situation. conclusion: this study points out that pediatricians tend to follow parents' position when confronted to parental opposition. in such situations, pediatricians go against their own decision in order to safeguard the parental alliance even if it leads to unreasonable obstinacy, thus conflicting with medical deontological code obligations. compliance with ethics regulations: yes. rationale: end-of-life management strategies are clearly a worldwide issue of major importance that intensivists have to deal with on a daily basis. advance directives may be the solution sought to guide physicians to take such difficult decisions. yet, health care directives are not legislated in tunisia. the objective of this project was to draw a general descriptive overview to assess patients' wishes in tunisia. patients and methods: data were collected from a -item-questionnaire based on the french intensive care society's form for advance directives which was filled by people of general population in tunisia, including doctors and paramedics, from may to mid-september . all people included were or older and well informed of the form's utility. results: a total of participants were included. the mean age was . ± . years with extremes of and and a sex ratio of . . fourty-one ( . %) were either doctors or nurses and ( %) did suffer from a severe medical condition. among all the participants, ( . %) thought that end-of-life decisions were up to the doctor. for the rest, they willingly chose to be hospitalized in an icu, to undergo cardiopulmonary rescuscitation and to have ventilation support with orotracheal intubation or tracheostomy respectively in ( . %), ( . %) and ( . %) of the cases. only ( . %) refused temporary dialysis. when asked about sequelae they can live with, participants accepted hemiplegia in . % and paraplegia in . % of the cases. on the contrary, ( . %) refused to live in permanent coma and ( . %) disagreed to undergo tracheostomy and ventilation for life. moreover, ( . %) found that serious un aesthetic sequelae was a fatal consequence they could not survive. as well, only ( . %) consented to live with deep intellectual deficiency. regarding palliative care, ( . %) participants wished to be profoundly sedated until death, ( . %) prefered to die home over ( . %) in hospital. sixtytwo ( . %) desired to see a representative of their religion. furthermore, ( %) were for organ donnation. gender, being a health care professional and age under versus equal or over were not significant in dependent factors (p > . ). conclusion: it is our duty ashealth care professionals to spread advance directives awareness and education. nevertheless, the law should keep the pace with ethics evolution. compliance with ethics regulations: yes. rationale: adapted organ support techniques are needed to enhance reliability of preclinical animal experiments in the intensive care setting (guillon, annals of intensive care- ). a few renal replacement therapy (rrt) models have already been developed in rats, mostly hemodialysis in chronic kidney disease models or hemofiltration techniques in sepsis experiments. mounting evidence from clinical (gaudry, nejm- ) and histopathological studies suggest that rrt for acute kidney injury (aki) could impair renal recovery by acting as a 'second hit' leading to a maladaptive repair of tubular epithelium. we aimed to study this hypothesis in a hemodialysis model in rats with septic aki. patients and methods: on day , sprague-dawley rats were injected with lipopolysaccharide or placebo (nacl . %) intraperitoneally. on day , anesthetized rats underwent femoral artery catheterization for hemodynamic parameters monitoring. at the same time, one femoral vein and one carotid artery were catheterized for arterio-venous sterile extracorporeal circulation with or without passing through a miniature sterile polyester sulfone hemodialyzer ( cm surface, kda pores, microkros ® ) filled with dialyzate liquid in the outer compartment (table ) . vessels were ligated after the procedure and rats allowed to awaken. on day , rats were sacrificed. results: all rats injected with lipopolysaccharides o :b mg/kg survived at day . anesthesia was much challenging: ketamine + xylazine and tiletamine-zolazepam + xylazine required induction and maintenance intraperitoneal injections. these medications induced important hemodynamic parameters fluctuations and high mortality. isoflurane gas inhalation enabled better stability, less hypothermia and quick awakening. adequate temperature was controlled with a heating pad during the procedure and an incubator after. supine position was maintained. the whole circuit was anticoagulated with ml of heparinized saline ui/ml, since clots occurred in the absence of anticoagulation and bleeding when higher dosing was used. circuit (< . ml including dialyzer) was filled with saline solution before initiation, and total restitution of blood at the end of the experiment prevented any blood transfusion requirement. hematocrit was determined at beginning ( %) and end of experiment ( %). a peristaltic pump provided a blood flow rate of . ml/min, (higher rate was not tolerated) for h. of note, rats who underwent sham procedure (vessels ligature only) survived and did not display aki. circulation of a counterflow dialysate in the dialyzer is planned but has not been performed yet. conclusion: this hemodialysis system for rats is feasible at a reasonable price and might help research involving rrt in either ckd or aki. compliance with ethics regulations: yes. there were no significant relationship between rri and past medical history or severity score. we observed a significant negative correlation between rri and diastolic arterial pressure (p = . ) and heart rate (p = . ) as it could be expected by rri formula. an increased rri was associated with higher potassium (p = . ) and higher creatinine levels (p = . ). although not significant, we found a higher rate of subsequent rrt in the high rri group ( % vs %, p = . ). over the first days, fluid balance was significantly different between groups ( ml vs - ml respectively for low and high rri group, p = . ). since standard of care were similar, this suggests different fluid volume status between the two groups. in the low rri group, the cause of aki could predominantly be prerenal since positive fluid balance was not explained by more severe aki with refractory oliguria as shown by the low rrt rate. nevertheless, we did not observed any relationship between rri and the evolution of serum urea or creatinine levels, nor with the presumed aetiology of aki. conclusion: when focussing on the first rri measurement once stage aki was reached, rri ≤ . seems to be in favour of prerenal and transient renal dysfunction even if this is not supported by creatinine serum evolution. compliance with ethics regulations: yes. rationale: critically ill patients are at higher risk of bleeding but also dialysis filter clotting (inflammatory state). intermittent hemodialysis with calcium-free citrate-containing ( . mmol/l) dialysate (cafcit-ihd) recently emerged as a new safe and simple alternative to continuous renal replacement therapy allowing heparin-free extended dialysis sessions (> h). in this study, we aimed to answer to two issues still unresolved: (i) can citrate contained in the dialysate accumulate and lead to citrate intoxication in patients with liver disorders, and (ii) can citrate be avoided using citrate-and calcium-free dialysate (ccf-ihd)? patients and methods: monocentric retrospective study. among the sessions performed with cafcit-ihd, the ihd sessions ( critically ill patients) with citrate measurement available before and after the dialysis filter were reviewed. estimation of the liver clearance was performed using the picco lemon ® system (pulsion). in addition, sessions performed using ccf-ihd were reviewed. results: all the patients had liver disorders (post-liver transplantation period n = ; cirrhosis with child > a ). among the eighteen cafcit-ihd patients, fifteen ( %) and six ( %) received mechanical ventilation or vasopressive drugs, respectively. the median time of the dialysis session was h [ ] [ ] [ ] [ ] , with hourly ultrafiltration rate of ml (one premature termination not related to dysfunctional catheter). in all patients, ionized calcium (ica) decreased below . mmol/l after the filter, whereas post-filter calcium reinjection according to ionic dialysance led to a stable pre-filter (i.e. patient) ica. median citrate concentrations were all below . mmol/l after the filter (minimal concentration to obtain anticoagulation mmol/l) and all except one below the normal value (< µmol/l) before the filter. during all the sessions, ionized to total calcium ratio was below . and the strong ionized gap decreased. when available (n = ), no correlation could be identified between serum citrate concentration and liver clearance. last, in ccf-ihd sessions performed in critically ill patients, no premature termination occurred (median time of the sessions h) and post-filter ica also decreased below . mmol/l. no citrate accumulation could be identified in critically ill patients (even with liver disorders) and receiving extended dialysis sessions ( h or more) using calcium-free citrate containing-ihd. interestingly, we demonstrated that citrate is not required to obtain optimal regional anticoagulation (i.e. post-filter ica < . mmol/l), and a citrate-and calcium-free dialysate could be a safe alternative. compliance with ethics regulations: yes. rationale: ventilator induced diaphragmatic dysfunction is highly prevalent in adult critical care and associated with worse outcomes. specificities in pediatric respiratory physiology suggest that critically ill children may be at high risk of developing this complication, but no study has described the evolution of diaphragmatic function in critically ill children undergoing mechanical ventilation. this study aims to validate a method to quantify diaphragmatic function in mechanically ventilated children. in this prospective single-center observational study, children between week and years old intubated for elective ent surgery and without pre-existing neuromuscular disease or recent muscle paralysis were recruited. immediately after intubation, diaphragmatic function was evaluated using brief airway occlusion maneuvers during which airway pressure at the endotracheal tube (paw) and electrical activity of the diaphragm (eadi) were simultaneously measured for consecutive spontaneous breaths, while the endotracheal tube was occluded with a specific valve. occlusion maneuvers were repeated times. in order to account for central respiratory drive and sedation use, we recorded the neuromechanical efficiency ratio (nme, paw/eadi), in addition to the maximal inspiratory force (mif). in order to determine the optimal measure of nme during an occlusion, the variability over the three occlusion maneuvers of different variables (first breath, last breath, breath with maximal paw deflection, breath with maximal nme value, and median nme value) was assessed using coefficients of variation and repeatability coefficients. results: patients had a median age of . years (interquartile range . - . ), a median weight of kg ( - ), and were male ( %). the median evolution of paw, eadi, and nme ratio over the occluded breaths are represented on fig. . nme values corresponding to the last breath and the breath with maximal paw deflection were the least variable, with median coefficient of variation of % and % and repeatability coefficients of . and . , respectively. conclusion: brief airway occlusions can be used to assess diaphragmatic function in intubated children through both mif and nme ratio, and the latter should ideally be computed on the last breath or the breath with the largest pressure deflection to improve repeatability and decrease variation. compliance with ethics regulations: yes. epidemiology is poorly understood due to the rare use of validated diagnostic tools. the main objective of the study was to determine, by systematically calculating the wat- score, the incidence of ws in our surgical picu. the secondary objective was to analyze the risk factors, consequences and management modalities of ws. patients and methods: following institutional review board approval, we conducted a prospective monocentric study between july and january . all consecutive mechanically ventilated children admitted in our surgical picu with sedation/analgesia by continuous intra-venous (iv) benzodiazepines (bzd) and/or opioids for at least h were included. as soon as sedation was decreased and during h following their total discontinuation, wat- score was assessed twice a day. ws was defined by a wat- score > . the search for risk factors and consequences associated with ws was performed by univariate analysis (mann-whitney and chi test). ethical standards were satisfied and the lack of opposition from patients and their parents was systematically checked. results: the incidence of ws was % among the patients of our cohort including % of children admitted postoperatively and % after severe traumatic brain injury (tbi). significant results are reported in table . our results show that even for sedation time less than days, children could develop ws ( / patients). on the other hand, age, severity (pelod score), number of previous surgeries and severe tbi were not associated with ws. our study also demonstrated that cessation of sedation and prevention of ws was not uniform in our unit. the high incidence of withdrawal syndrome in our study, even in children sedated for less than days, and its consequences require thinking about prevention. we suggest a systematic monitoring of the occurrence of this adverse event using a validated score, from days of continuous iv sedation/analgesia. compliance with ethics regulations: yes. rationale: severe traumatic brain injury (tbi) is a major healthcare problem. amplitude and duration of intracranial hypertension is highly associated with patient outcome. the intracranial pressure (icp) is therefore one key parameter to monitor in the acute phase. when icp is monitored with an external ventricular drain, the pressure recorded by the monitor does not always correspond to the real icp, depending on the status (open/closed) of the -way tap. misleading values could therefore be sent to the patient medical record. our hypothesis is that a machine-learning algorithm will be able to identify automatically and in real time the reliable and non-reliable values of the icp signal. we retrospectively studied pediatric patients having an external ventricular drain between july and july , in a single pediatric intensive care unit. the icp signals were extracted from a high-frequency database ( hz) and pre-processed adequately. to train the algorithms, an annotated database was manually created with two classes: reliable icp vs. non-reliable icp (drain system opened to allow cerebrospinal fluid removal). eleven signal characteristics were compared between the two classes (mann-whitney test), and significantly differing variables were tested in the algorithms. we compared the performance of two machine-learning algorithms: the k-nearest neighbors (knn) and the support vector machine (svm). using -fold cross-validation method, % of the data was used to train the algorithms and % was used for testing. the best classifier was further validated by simulating a real-time icp analysis, using a s sliding-window approach with % overlap. the study was approved by the localresearch ethics committee. results: sixteen patients were included in the study. the training database created from patients, contained segments (of s duration) per class and per patient. eight signal variables were identified and kept to define the segments. the knn algorithm, with k = , led to the best performance, with a mean of % (mean ± sd: % ± . %). the knn was then visually validated on icp signals from the remaining two patients ( figure) . by simulating a real-time icp extraction, our algorithm was able to efficiently identify the reliable icp segments, and to display a mean value only for valid segments. university hospital picu (paris). all consecutive children ( month- years) admitted for acute encephalitis were included and diagnosis was confirmed using the consensus conference criteria's. data regarding clinical, biological and radiological presentations were collected as well as data on the therapeutics used and outcomes at discharge and at the last medical consultation. results: patients were included with a mean age of . years (range . to years old). infectious causes were identified in % (n = ), autoimmune causes in % (n = ) and acute demyelinating encephalomyelitis in % (n = ) of cases. etiology remained undetermined in % of cases (n = ). the most common pathogens were, in order of frequency, influenzae virus, mycoplasma pneumoniae and epstein-bar virus. the main clinical features were fever ( % n = ); epileptic seizures ( % n = ) and coma ( % n = ). regarding therapeutics, % of patients required mechanical ventilation and % of patients required hemodynamic support. % received corticosteroids, % intravenous immunoglobulins and % plasmatic exchanges. the use of these specific treatments was heterogeneous, especially in infectious and undetermined encephalitis, where respectively % and % received boluses of corticoids. the mean length of stay in picu was . days (range - days). the mortality rate was % and the overall rate of sequelae at discharge was % and % at distance, with % considered as severe (gose-ped score > ). the use of mechanical ventilation and young age at diagnosis were risk factors associated with poor prognosis at discharge. the etiology of acute encephalitis remains indeterminate in more than % cases with a clear predominance of infectious causes when an etiology is found. this is a severe pathology responsible for significant mortality and morbidity requiring long-term follow-up. compliance with ethics regulations: yes. rationale: preserving neurological outcome of children under extracorporeal membrane oxygenation (ecmo) remains challenging. acute brain injury (abi) is a frequent complication of ecmo that could be prevented by continuous neuromonitoring. cerebral near infrared spectroscopy (nirs) is routinely used for detecting cerebral complications of cardiac surgery. in adults and infants under prolonged ecmo, cerebral hypoxia is associated with poor neurological outcome. the aim of this study was to assess the value of an impaired cerebral oxygenation on mortality and occurrence of an abi in children under ecmo. patients and methods: children under years old were included in this observational retrospective monocentric study if they needed veno-venous (v-v) or veno-arterial (v-a) ecmo for respiratory and/ or circulatory failure and had concomittant nirs monitoring. cerebral desaturation was defined as a rsco value under % or under % from the baseline; cerebral hyperoxia was defined as a rsco value above %. proportion of time in cerebral desaturation and hyperoxia were recorded. neurological lesions were identified on imaging (mri or scan) by blinded radiologist and classified as major or minor. abi was defined as any hemorragic or ischemic lesion on cerebral imaging, including brain death. results: patients were included. ecmo duration was [ ; ] days. the mortality rate was ( . %), and the proportion of abi was ( %) including brain deaths, ( . %) major lesions, and ( . %) minor lesions. mean rsco was ± % in the right hemisphere, and ± % in the left hemisphere. there was no significant difference in cerebral hypoxia between survivors and non survivors, and between patients with and without an abi. cerebral hyperoxia was associated with a better survival (p = . in the right hemisphere, and p = . in the left hemisphere). in v-v ecmo and at the right conclusion: in our study, cerebral hypoxia was not associated with poor neurological outcome, but cerebral hyperoxia seems to be protective especially in v-v ecmo. this is the first study assessing the value of cerebral oxymetry in all age ranges pediatric ecmo. in this population, multimodal monitoring might be better than nirs alone to predict neurological impairment. further prospective studies are needed to assess first the feasibility, then the impact of such a monitoring. compliance with ethics regulations: yes. cerebral autoregulation impairment is associated with acute neurological events during pediatric extracorporeal membrane rationale: children supported by extracorporeal membrane oxygenation (ecmo) present a high risk of adverse neurological complications. as some animal studies have shown, cerebral autoregulation (ca) impairment after exposure to ecmo, may be a key factor. our main objective was to investigate the feasibility of ca continuous monitoring during ecmo treatment. the second objective was to analyze the relationship between ca impairment and neurological outcome. patients and methods: an observational prospective study including children treated by ecmo in centers was conducted. a correlation coefficient between the variations of regional cerebral oxygen saturation (rsco ) and the variations of mean arterial blood pressure(map) was calculated as an index of ca (cerebral oxygenation reactivity index, cox) during ecmo. a cox > . was considered as indicative for dysautoregulation. cox values were averaged inside mmhg-map bins, allowing determining optimal map (mapopt) and lower (lla) and upper (ula) limits of autoregulation in -h periods. neurological outcome was assessed by the onset of an acute neurologic event (ane) defined by occurrence of hemorrhagic or ischemic stroke and/ or clinical or electrical seizure and/or brain death during the ecmo treatment. rationale: myocardial ischemia reperfusion (ir) injury is the leading cause of perioperative morbi-mortality. protective effect of pharmacologic preconditioning such as anesthetic preconditioning (apc) with sevoflurane (sev) has been widely demonstrated in animal and human models. apc seems to protect myocardial cells from apoptosis, a programmed process of cell death tightly controlled by bcl- family proteins. however, the involved mechanisms in apc have yet to be characterized. we hypothesized that apc protects against myocardial apoptotic cell death by regulating bcl- anti-apoptotic members. to study the sev-induced apc mechanisms against myocardial ir, we used a validated in vitro model reproducing ir injury. rat cardiomyoblast cells h c were cultivated in . % o hypoxia in the presence of ischemia-mimicking medium. after min of ischemia, the reperfusion injuries are induced by replacing the culture medium with a krebs-henseleit normoxic medium for min. apc was performed by adding sev directly into the culture medium at an initial concentration of mm, prior to ischemia, for min. we then used another preconditioning agent, metformin (met), to explore the same signaling pathways. apoptotic cell death was measured by caspase activity assay and western blotting (expression of cleaved caspase ) under ir and apc conditions. results: our model faithfully reproduced the protective effect of apc which results in a significant decreased apoptosis under ir ( % reduction of the caspase enzymatic activity, correlated with a decrease of caspase cleavage). we showed that sev induces overexpression of the anti-apoptotic protein bcl-xl, which is responsible for the protective effect of apc. furthermore, these observations were confirmed in vivo in mouse heart lysates. we demonstrated that bcl-xl overexpression was due to the activation of the protein kinase akt. interestingly, we were able to show that preconditioning with met reproduces the protective effect of sev by inducing an akt-dependent bcl-xl overexpression. indeed, sev and met, which are both complex inhibitors of mitochondrial respiratory chain, seem to share a common reactive oxygenated species-dependent protective mechanism responsible for bcl-xl protein regulation. rationale: despite early endovascular treatment with successful recanalization, % of acute ischemic stroke (ais) patients experience a poor functional outcome after a large vessel occlusion. sepsis is frequent at the acute phase of stroke and is associated with poorer short and long term outcomes. we aimed to investigate the cerebral consequences of sepsis after recanalized ais and explore possible mechanisms involved. patients and methods: male c bl mice were randomly assigned to a x factorial plan to one of the following groups: ) a -minute middle cerebral artery (t-mcao) transient occlusion under inhaled general anesthesia, followed min after recanalization by intraperitoneal (i.p.) sepsis (lps, µg/g diluted in µl of nacl . %), (tmcao/ lps group); ) t-mcao followed by i.p. placebo ( µl of nacl . %) (tmcao/placebo group); ) sham operation (cervicotomy without carotid catheterization) followed by i.p. lps. (sham/lps group); ) sham operation followed by i.p. placebo, (sham/placebo group). in all groups, animals received subcutaneous fluid resuscitation ( µl nacl . %) immediately after the procedure and h later. twenty-four hours after recanalization, animals were scored for sepsis features and neurological deficit (on the modified neurological severity scale), (mnss) before sacrifice. the primary outcome measurement was a composite of death and hemorrhagic transformation at h. secondary outcome measurements included neurological deficit, sepsis features, neutrophil activation reflected by plasmatic myeloperoxydase (mpo) levels, stroke volume, and microglial activation in brain parenchyma (infarct core, perilesional area, controlateral hemisphere). results: t-mcao/lps animals had higher mnss ( . fold, p = . ) and sepsis ( fold, p = . ) scores at h with increased plasma mpo levels at h ( . fold, p < . ) and h ( . fold, p < . ), as well as, lower temperature ( . °c reduction, p = . ) and glycemia ( . g/l reduction, p = . ) as compared to tmcao/placebo animals. t-mcao/lps animals had a higher risk of unfavorable outcome at h ( -group comparison: p = . ; x analysis: t-mcao/lps, / − %vs. t-mcao/placebo / - %-, p < . ), whereas stroke volumes were not significantly different between groups. detailed results are presented in table . compared to t-mcao/placebo group, t-mcao/ lps animals had . fold increase (p = . ) in the mean number of microglial cells in the hemisphere controlateral to t-mcao, whereas no significant difference was observed in infarct core or peri-infarct parenchyma. conclusion: early sepsis after experimental ais worsens outcome and neurological deficit, without impacting stroke volume. early sepsisinduced systemic activation of neutrophils and increased microglial activation in the hemisphere contralateral to ischemia may have an important role on neurological outcomes observed in this setting. compliance with ethics regulations: yes. rationale: extracellular vesicles (evs) regulate diverse cellular and biological processes via facilitating intercellular cross-talk. several studies have suggested an association between lung injury and the generation of evs derived from platelets, neutrophils, monocytes, lymphocytes, red blood cells, endothelial cells, and epithelial cells. every year more than , patients require cardiac surgery with cardiopulmonary bypass (cpb). this cpb allows a substitution of the heart pump function and an oxygenation of the blood permitting a stop of the mechanical ventilation (mv). stopping mv during cpb is responsible for lung damage, leading to postoperative systemic inflammation while maintaining mv with positive expiratory pressure (peep) diminished the occurrence of atelectasis and the postoperative inflammatory response. in addition, this surgery is marked by immune dysfunction, leading to real immunosuppression of patients in postoperative care. a link between pulmonary injury and postoperative immunosuppression has been established, however, the mechanisms underlying this association are not fully known and evs may have a role in this post-operative immunosuppression. the purpose of this study is to investigate whether lung injury induced during cardiac surgery with cpb lead to the emergence of evs. the effect of mv during cpb on the production of these evs has also been studied. patients and methods: patients were prospectively divided into two groups: without mv during cpb and dead space mv with positive end-expiratory pressure during cpb. pao (arterial oxygen tension)/ fio (inspired oxygen fraction) ratio, biological markers of lung injury (cxcl , ccl , tnf-α, il- β, il- , rage, il- ) and blood cell count were collected before, h and days after surgery. the quantification of plasma evs was performed using turnable resistive pulse sensing and characterization of evs was performed using flow cytometry before, h and days after surgery. rationale: the benefit of prone positioning (pp) during moderate to severe acute respiratory distress syndrome (ards) may be related to its impact on the inflammatory response to ventilator-induced lung injuries. [ c]-pk is a positron emission tomography (pet) radiotracer that allows the non-invasive quantification of macrophages. we aimed to evaluate the effects of pp on [ c]-pk lung uptake in animals with experimental ards. patients and methods: experimental ards (by hydrochloric acid) was induced in pigs in supine position (sp), to obtain a pao / fio < mmhg. animals were under general anesthesia, neuromuscular blockade, and ventilated with a ml kg − tidal volume, and cmh o of positive end-expiratory pressure (peep). immediately after experimental ards, animals were randomized to be prone positioned, or to remain in sp. pet and computerized tomography (ct) were acquired h after randomization (h ). [ c]-pk uptake was measured on the whole lungs, and by dividing the lungs into regions or slices-of-interest (soi) along the ventro-dorsal axis, and was quantified by the standardized uptake value (suv), corrected for lung tissue density. results: pp was performed in animals, and sp in . after ards induction, pao /fio was [iqr, [ . - . ] in sp animals (p = . ). in pp animals, [ c]-pk suv was significantly lower in ventral soi, compared to sp, and significantly increased in dorsal soi ( fig. , *: p < . between groups in a given soi). in univariate analysis, [ c]-pk regional suv was positively associated with regional ct-measured peep-related increase in gas volume, and negatively with peep-related lung recruitment, but not with regional tidal volume. conclusion: during experimental ards, pp redistributed lung macrophage recruitment estimated by [ c]-pk uptake from ventral lung regions to dorsal regions, without affecting global macrophage influx. the intensity of macrophage recruitment was associated with peep-related lung inflation. compliance with ethics regulations: yes. rationale: acute respiratory distress syndrome (ards) is a pleiomorphic disease characterized by a severe respiratory failure associated with an increased mortality. nowadays, predicting clinical outcome of patients suffering from ards remains difficult. therefore, identifying new biomarkers to predict patient outcome, to evaluate response to therapy and to identify new potential pathways of interest are highly needed. exosomes are extracellular vesicles involved in cell-cell communication by transferring micrornas (mirnas) from donor to recipient cells. thus, exosomal mirnas can significantly affect biological pathways within recipient cells resulting in alterations of cellular function and the development of a pathological state. as biomarkers are highly needed in the particular field of ards, we realized a monocentric and prospective study to identify a new potential biomarker of interest. therefore, a prospective plasma sampling at the diagnosis of moderate to severe ards according to the definition of "berlin" has been performed. we analysed mirna content of exosomes from plasma ards patients compared to healthy subjects (hs) in order to identify new potential predictive biomarkers in ards. during one-year period, patients hospitalized in the icu of chu sart tilman suffering from infectious moderate-to-severe ards have been included. the ethical committee review boards of the hospital approved the research protocol (b , ref: / ), and informed consents were obtained. exosomes were isolated from plasma samples of ards patients and hs with standard ultracentrifugation protocol. exosomal mirna content was analyzed using small rna sequencing method, and diseases/biological processes associated to altered mirs were determined by bioinformatic analysis. results: for the first time, exosomal mirna expression modifications were studied in patients with moderate-to-severe infectious ards. we identified a new signature statistically significant composed of three up-regulated mirnas (mir- , mir- a and mir- ) and one downregulated (mir-let- b). conclusion: we identified potential biomarkers for ards from plasma exosomes. our findings may thus lead to predict ards outcome but also a better understanding about the roles of these mirs in the pathogenesis of ards and thus open new avenues for therapeutic approaches. in particular, exploit and develop the pro-fibrotic pathway induced by down-expression of mir-let- b. but also confirm in the future the current interest about mir- in its ability to restore pulmonary integrity after trauma. compliance with ethics regulations: yes. rationale: diabetic ketoacidosis (dka) is a life-threatening emergency. microvascular hyporeactivity was reported in these patients and was completely reversibly when ph was corrected with treatment: aggressive rehydration, electrolyte replacement and insulin therapy ( ) . red blood cell (rbc), a component of the microcirculation, showed alterations oftheir shape in diabetic patients ( ) but no data were available concerning the time course of the rbc deformability during treatment for dka. we aimed to assess the rbc deformability during dka treatment in icu patients. patients and methods: after approval by the ethics committee, rbcs deformability was assessed, in all icu patients admitted for dka and without infection, by ektacytometry technique (laser-assisted optical rotational red cell analyzer-lorrca): at icu admission, + h, + h and at the end of the icu stay ( - h). elongation index (ei) was defined as (l − w)/(l + w), where l is the length and w is the width. at °c, ei values were determined in the function of shear stress (ss) in a range of . - pa, based upon the laser diffraction pattern changes. a higher ei indicates greater rbc deformation. rbc deformability from patients with dka was compared at icu admission to healthy volunteers (v) and to diabetic patients followed in consultation (d). we also studied the evolution of deformability during treatment. results: icu dka patients compared to d and v were studied. as expected, glycemia and glycated hemoglobin were significantly higher in dka compared to d (respectively: glycemia: ( - ) vs ( - ) mg/dl and . % ( . - . ) vs . ( . - . ); all p < . ). dka patients received ( - ) ml of fluids and . ui/ kg bw ( . - . ) of insulin during their first h of icu stay. rbcs deformability from dka patients was significantly more altered at icu admission compared to others groups ( fig. ) and these alterations persists despite treatment. no correlations were observed between these alterations and quantity of fluids or insulin received, glycemia, glycated hemoglobin, ph, natremia, age or length of diabetes history. conclusion: in contrast of reversible microvascular hyporeactivity, rbc deformability from dka patients was already altered at icu admission and remains altered despite treatment. these alterations could contribute to the blood flow abnormalities observed in these patients. compliance with ethics regulations: yes. rationale: sepsis remains the first cause of acute circulatory failure in the emergency department (ed). standardized fluid resuscitation may not be adapted in certain patients, especially those with early sepsisinduced cardiac dysfunction in whom excessive fluid administration could be deleterious. information on early hemodynamic profile of septic patients in the ed are scarce. accordingly, we aimed at describing hemodynamic profiles encountered in septic patients assessed shortly after their ed admission using focused echocardiography. patients and methods: we prospectively enrolled adult patients with sepsis (qsofa score ≥ ) from january to july in the ed (nct ). focused echocardiography were performed by emergency physicians previously trained to ecmu level. each patient was evaluated according to a standardized protocol based on a limited number of simple binary clinical questions. investigators interpreted on-line the echocardiographic examination, determined the hemodynamic profile based on simple yet robust criteria (hypovolemia, left ventricular [lv] or right ventricular [rv] failure, vasoplegia with hyperdynamic state, tamponade, severe mitral or aortic regurgitation, or apparently normal profile), and recorded any substantial change in planned therapeutic management (surviving sepsis campaign ). data were digitally stored and validated off-line by an expert in critical care echocardiography. results: focused echocardiography were performed in patients (mean age: ± years; men: %; source of infection: pulmonary %, urinary %, abdominal %) after a median fluid loading of ml (iqr: - ml). according to sepsis- definition, patients had sepsis and sustained septic shock. mean sofa score was . ± . (hemodynamic failure %, respiratory failure %, renal failure %), mean lactate reached . ± . mmol/l, icu admission involved % of patients and overall -day mortality reached %. hemodynamic profile was hypovolemia in patients ( %), vasoplegia in patients ( %), cardiac failure in patients ( %) (lv failure: n = ; rv failure: n = ) and without relevant hemodynamic abnormality in patients ( %). ongoing therapy was altered based on early echocardiographic assessment in % of cases. mortality rate was not significantly different between groups (p = . ). conclusion: although hypovolemia was predominantly identified in patients presenting to the ed with sepsis during hemodynamic assessment, early ventricular dysfunction involved one-quarter of patients. these results suggest that early focused echocardiographic assessment promises to help the front-line physician tailoring the therapeutic management of septic patients in ed, especially regarding fluid resuscitation. compliance with ethics regulations: yes. right ventricular failure in septic shock characterization, incidence and impact on fluid-responsiveness guillaume geri , amélie prigent , xavier repessé , marine goudelin , gwenael prat , bruno evrard , cyril charron , philippe vignon , antoine vieillard-baron ambroise paré hospital, boulogne-billancourt, france; ambroise paré hospital, medical icu, aphp, boulogne-billancourt, france; chu limoges, limoges, france; chu brest, brest, france correspondence: guillaume geri (guillaume.geri@aphp.fr) ann. intensive care , (suppl ):f- rationale: right ventricular (rv) failure was defined by rv dilatation with systemic congestion. tricuspid annular plane systolic excursion (tapse) could be of limited value. we report the incidence of rv failure in patients with septic shock, its potential impact on the response to fluids, as well as tapse values. patients and methods: ancillary study of the hemopred prospective multicenter study including patients under mechanical ventilation with circulatory failure. with septic shock were analyzed. patients were classified in groups based on central venous pressure (cvp) and rv size (rv/lv end-diastolic area, eda). in group , patients had no rv dilatation (rv/lveda < . ). in group , patients had rv dilatation (rv/ lveda ≥ . ) with a cvp < mmhg (no venous congestion). rv failure was defined in group by rv dilatation and a cvp ≥ mmhg. passive leg raising (plr) was performed. results: % of patients were in group , % in group and % in group . in group and , rv/lv eda was higher than in group , . [ . ; . ] versus . [ . ; . ]. cvp was [ ; . ] mmhg in group . a correlation between rv size and cvp was only observed in group . higher rv size was associated with a lower response to plr (figure) . a large overlap of tapse values was observed between the groups. . % of patients with rv failure had an abnormal tapse. conclusion: rv failure is frequent in septic shock and alters fluid responsiveness. tapse was not accurate enough to diagnose rv failure. compliance with ethics regulations: yes. rationale: weaning-induced pulmonary oedema (wipo) is a leading cause of weaning failure in high-risk patients (heart failure, copd, obesity). we hypothesized that hypervolemia associated with positive fluid balance facilitates wipo in high-risk patients. patients and methods: in this prospective, observational, singlecenter study, patients with copd and/or heart failure with reduced ejection fraction (< %) were studied. exclusion criteria were nonsinus rhythm, severe mitral valve disease and inability to obtain adequate echocardiographic views. echocardiography was performed immediately before and during spontaneous breathing trial (sbt, -min t-tube). patients who failed sbt were treated according to echocardiographic results before undergoing a second sbt. fluid balance and body weight were collected at each sbt. shows interesting performance to predict fluid responsiveness in spontaneously breathing patients. nevertheless, measurement sites of inferior vena cava (ivc) diameters remain controversial for that purpose. the aim of the study was to test the accuracy of different measurement sites of civc to predict fluid responsiveness in spontaneously breathingpatients. this study is a post hoc analysis of two prospective cohorts. we included spontaneously breathing patients without mechanical ventilation presenting with sepsis-related acute circulatory failure and considered for volume expansion (ve). we assessed hemodynamic status at baseline and after a fluid challenge (fc) induced by a min-infusion of ml-gelatin %. the ivc diameters were measured off-line with ultrasonography using the bi-dimensional mode on a subcostal long-axis view. the civc was calculated as [ (expiratory-inspiratory)/expiratory] diameters during standardized (civc-st) and unstandardized breathing (civc-ns) conditions. breathing standardization consisted of a deep inspiration with concomitant control of buccal pressures and passive exhalation. patients were referred to be responders to fc (i.e. fluid responsive) when the stroke volume increased by ≥ %. results: among the patients included in the study, ( %) were responders to fc. the accuracy of civc-st and civc-ns before fc to predict fluid responsiveness differed significantly by measurement sites (interaction p value < . and < . , respectively). measuring ivc diameters cm from the junction of the ivc and the right atrium provided the best accuracy to predict fluid responsiveness ( fig. ). at cm caudal to the right atrium, civc-st was significantly better than civcns to predict fluid responsiveness: area under roc curve . ( % ci . - . ) versus . ( % ci . - . ), p < . . at cm, a civcst ≥ % and a civc-ns ≥ % predicted fluid responsiveness with sensitivity of % and %, and specificity of % and %, respectively. conclusion: accuracy of civc to predict fluid responsiveness in spontaneously breathing patients depends on both measurement sites of ivc diameters and breathing conditions. measuring ivc diameters during a standardized inspiration maneuver at cm caudal to the right atrium is the most relevant mean to optimize civc performance to guide ve. compliance with ethics regulations: yes. rationale: intermittent hemodialysis (ihd) is increasingly used in patients admitted to intensive care unit (icu) with acute kidney injury (aki) requiring renal replacement therapy (rrt). however, this technique is associated with nearly % of episodes of perdialytic hemodynamic instability (hi), a common cause of increased morbidity and mortality. at the same time, trans-thoracic echocardiography (tte) has become widely used in intensive care units and is now one of the hemodynamic monitoring methods used daily in the icu setting. patients and methods: search for one or more pre-dialysis tte criteria predictive of perdialytic hi, defined by a systolic blood pressure (sbp) lesser than mmhg or a suddain decrease in sbp of more than mmhg. prospective, observational study of standard care in a medical icu. collection of demographic, clinical and pre-dialysis echocardiographic data from included patients. results: twenty-five patients with a total of sessions of ihd between november and november were included in the study. tte was performed for each patient before each ihd session. hi occurred in hemodialysis sessions. in univariate analysis, the existence of prior heart disease ( % vs %, p = . ), a greater diameter of the left atrium ( . vs . cm, p = . ), a lower cardiac output ( . vs . l/min, p = . ), a right dysfunction assessed by lowered tapse and s-wave ( vs mm, p < . and . vs . cm/s, p = . , respectively) and an increase in paps ( vs mmhg, p = . ) were significantly associated with the occurrence of perdialytic hi (fig. rationale: several transthoracic echocardiography (tte) parameters of left (lv) and right ventricular (rv) systolic function are available. we compared the ability of these different parameters to track changes in lv or rv systolic function and to detect lv or rv systolic dysfunction in critically-ill patients. in patients ( mechanically ventilated and with atrial fibrillation), tte examinations were performed before and after i) infusion of -ml of saline (n = ), ii) changes in norepinephrine (n = ), iii) or in dobutamine (n = ) dosage. for the lv systolic function, we compared the mitral annular plane systolic excursion (mapse), the systolic (s') peak velocity of the lateral mitral annulus and the global longitudinal strain (glslv) to the lv ejection fraction (lvef), considered as the gold standard. for the rv systolic function, we compared the tricuspid annular plane systolic excursion (tapse), the systolic peak (s) velocity of the tricuspid annulus and the global longitudinal strain (glsrv) to the rv fractional area change (fac), considered as the gold standard. results: after pooling all values, lvef ( ± % at baseline) was better correlated to glslv (r = . ) than to mapse (r = . ) and s' wave (r = . ) (each p < . ). the concordance rate between changes (in %) in lvef and in the other parameters of lv systolic function was % for glslv, % for mapse and % for s' wave. both mapse and s' wave could not reliably detect moderate ( % ≤ lvef ≤ %) or severe (lvef < %) lv dysfunction. conversely, a glslv > − % predicted moderate lv dysfunction with a sensitivity of % ( % ic: - %) and a specificity of % ( % ic: - %) and a glslv > − . % predicted severe lv dysfunction with a sensitivity of % ( % ic: - %) and a specificity of % ( % ic: - %). after pooling all values, fac ( ± % at baseline) was better correlated to glsrv (r = . ) than to tapse (r = . ) and s wave (r = . ) (each p < . ). the concordance rate between changes (in %) in fac and in the other parameters of rv systolic function was % for glsrv, % for tapse and % for s wave.both tapse and s wave could detect rv dysfunction (fac ≤ %) with moderate reliability only. conversely, a glsrv > − % detected rv dysfunction with a sensitivity of % ( % ic: - %) and a specificity of % ( % ic: - %). in critically-ill patients, glslv and glsrv seem to be the best tte parameters of lv and rv systolic function. enrolments are still ongoing, which may allow further analysis. compliance with ethics regulations: yes. rationale: passive leg raising (plr), pulse pressure variation (ppv), and the -second end-expiratory occlusion test (eexpo) are frequently used to assess preload responsiveness. however, there are conditions in which they are not valid or feasible, which may preclude their applicability in the daily clinical practice. the aim of this study was to estimate the prevalence of such conditions in critically ill patients with acute circulatory failure. between january and april , all patients of a -bed medical icu were daily screened and those with acute circulatory failure, defined by norepinephrine infusion or fluid therapy > l during the previous h, were included. in each of them, we screened the criteria of validity/feasibility of ppv, plr and eexpo. results: eighty-four patients ( % with septic shock, % with cardiogenic shock, % with hypovolemic shock, % with non-septic vasoplegic shock) were enrolled in the study. among them, norepinephrine infusion was ongoing at the time of enrolment in % of the patients whilst % were under mechanical ventilation, and % with acute respiratory distress syndrome. plr was not applicable in % of cases. this was mainly due to venous compression stocking ( % of cases), intra-abdominal hypertension ( % of cases), and either an absence of cardiac output monitoring or impossibility to perform echocardiography ( % of cases). among the intubated patients, ppv was applicable in % of cases, including cases with high ppv under conditions generating false negatives (low tidal volume or lung compliance) or low ppv values under conditions generating false positives (spontaneous breathing, cardiac arrythmias). however, ppv was not interpretable in % of cases. this was mainly due to low tidal volume ventilation ( % of cases), spontaneous breathing activity ( % of cases), while the remaining non-interpretable cases ( %) had more than one reason. in the intubated patients, eexpo was not applicable in % of cases. this was due to impossibility for patients to sustain a -s hold of mechanical ventilation in % of cases, and either an absence of cardiac output monitoring or the impossibility to perform echocardiography in % of cases. plr and eexpo were both valid and feasible in % of the patients, and the three tests were all feasible in only % of patients. rationale: comorbid association between chronic respiratory diseases and sleep apnea syndrome (sas) revealed frequent with systematic search in icu following icu stay. this association carries prognosis impact depending whether specific treatment is implemented or not. nosas and stop bang scores are proposed for screening of sas in general population. the aim of the present study is to report the prevalence of sas in icu patients admitted for hypercapnic respiratory failure and compare association of nosas and stop bang score with sas severity. the study was conducted between january and september . patients consecutively admitted in the icu for hypercapnic respiratory failure had calculation of a no sas and stop bang scores at admission. in survivors nocturnal polygraphic records was performed to weeks following icu discharge. the association between the number of apnea-hypopnea episodes, bmi, and clinical variables suggestive of sas, was tested by poisson regression model. results: during the study-period, patients (mean age: ± years, ph . ± . , paco ± ) were admitted for hypercapnic respiratory failure. non invasive ventilation was used in % and death occurred in six patients. polygraphic records were performed in ( lost to follow-up) mean apnea-hypopnea index was ± with a minimum of and a maximum of . poisson logistic regression showed that no sas (p = . ) but not stop bang (p = . ) was associated with the level of apnea-hypopnea index. rationale: patients with severe acute exacerbations of chronic obstructive pulmonary disease (copd) may benefit from high-flow nasal oxygen regarding its physiological effects and good tolerance. bronchodilator vibrating mesh nebulization through high-flow nasal oxygen circuit has been described to induce similar effect to standard facial mask jet nebulization in stable copd patients. we aim to evaluate whether vibrating mesh nebulization of salbutamol through highflow nasal oxygen circuit is efficient in unstable patients with copd. patients and methods: we conducted a monocenter non-randomized physiological prospective cross-over study, between january and september , including icu patients with severe acute exacerbation of copd and respiratory acidosis treated by salbutamol nebulization. spirometry and airway resistances records were performed after a -h wash-out period without bronchodilator, before and after vibrating mesh nebulization of mg salbutamol through high-flow nasal oxygen circuit. the primary endpoint was forced expiratory volume in s after salbutamol nebulization. secondary endpoints included other spirometry parameters, clinical parameters, dyspnea assessed by a borg scale. results: fourteen consecutive patients were included, forced expiratory volume in s increased significantly after salbutamol nebulization through high-flow nasal oxygen ( ± ml, p = . ), as well as forced vital capacity ( ml ± , p = . ). airway resistances were not significantly changed after nebulization (− . ± . , p = . ) as well as peak expiratory flow (+ ml ± , p = . ). no difference was observed on borg scale (p = . ) and respiratory rate (p = . ) after salbutamol nebulization, while heart rate increased significantly (p = . ). discussion: salbutamol nebulization using vibrating mesh nebuliser placed on high-flow nasal oxygen circuit induces a significant but moderate bronchodilation in patients with severe acute exacerbation of copd. moreover, improvement of forced vital capacity after salbutamol nebulization suggests a reduction of dynamic hyperinflation. conclusion: salbutamol vibrating mesh nebulization through highflow nasal oxygen circuit increases significantly forced expiratory volume in s. compliance with ethics regulations: yes. t-piece versus sub-therapeutic pressure support for weaning from invasive mechanical ventilation in patients with chronic obstructive pulmonary disease: a comparative prospective study amira jamoussi, fatma jarraya, samia ayed, takoua merhabene, jalila ben khelil, mohamed besbes abderrahmen mami hospital, tunis, tunisia correspondence: amira jamoussi (dr.amira.jamoussi@gmail.com) ann. intensive care , (suppl ):f- rationale: the best weaning strategy for patients with chronic obstructive pulmonary disease (copd) remains unknown. the spontaneous breathing trial (sbt) represents a crucial step of weaning, but the choice between the t-piece (sv-tube) or the sub-therapeutic setting of the level of pressure support without positive expiratory pressure (psv) is still a matter of debate. we aimed to compare the success of extubation between two groups of copd patients according to the sbt type (vs-tube vs psv). patients and methods: it was a prospective and comparative study, from april to march , at the abderrahmen mami hospital's intensive care unit (icu). copd patients who underwent invasive mechanical ventilation (mv) for at least h and met the criteria for weaning were included and randomized to sv-tube or psv. a multivariate analysis was performed to determine the association between the sbt modality and the success of extubation (no re-intubation during the h following extubation). results: during the two years' study, patients were included. the mean age was ± years, the sex-ratio was . . weaning process was simple in patients ( %), difficult in patients ( %) and prolonged in patients ( %). fifteen and patients were respectively randomized to the sv-tube and psv groups. the mean duration of mv before randomization was comparable between the groups (sv-tube . ± . days vs psv . ± . days, p = . ). mean weaning time (days) was . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] for the sv-tube group and . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] for the psv group. the mean total mv duration (days) was higher in the sv-tube group than in the psv group ( . vs . , p = . ). the number of re-intubated patients within h following extubation was higher in the psv group ( / vs / , p = . ) as well as the overall reintubation rate ( . % vs %, p = . ). in multivariate analysis, the sbt's trial was independently associated to the success of extubation (or = . , ic [ . - . ], p = . ) in favor of sv-tube' modality. the median length of stay in intensive care was days [ ; ]. the mortality was higher in the psv group ( / vs / , p = . ). extubation failure was a factor associated with mortality (or = . , ci [ . , . ], p = . ). conclusion: ventilation weaning was easy in % of intubated copd patients. sv-tube as sbt modality was associated to success of extubation in patients with copd. mortality in intensive care was significantly higher in re-intubated patients. compliance with ethics regulations: yes. rationale: non-invasive ventilation has become the mainstay in hypercapnic respiratory failure. delaying intubation and invasive ventilation is associated with a worse outcome in these patients. although a predictive score of niv failure has been validated for hypoxemic respiratory failure no such score exists in hypercapnic respiratory failure. the aim of our study is to compare the performance of two scores in the predictive niv failure hypercapnic respiratory failure. patients and methods: consecutive patients admitted between january and july for hypercapnic respiratory failure, were included. hacor score and rox score were calculated in each patient at admission. in patients ventilated non-invasively, the outcome (niv success or failure) was noted. the area under curve (auc) and operative characteristics were computed for both scores. results: during the study-period, out of patients admitted for hypercapnic respiratory failure received niv as the primary ventilatory mode. these patients were mainly men ( / ), had a mean age of . ± years and had the following pulmonary disease: copd exacerbation . %, obesity-hypoventilation syndrome . %, bronchiectasis . %, and other diseases: . %. niv failure occurred in patients ( . %) and icu mortality in . %. mean hacor score and rox score were . ± . and . ± , respectively. the auc under roc was higher for hacor than rox ( . and . respectively) ( fig. ). the hacor score (cut-off ) had a sensitivity of . and specificity of . . conclusion: hacor score seems more accurate in predicting niv failure in hypercapnic respiratory failure. further prospective validation is needed. compliance with ethics regulations: na. rationale: published data on outcomes in respiratory weaning centers are limited and seem to depend on the organisation of healthcare systems and patient case-mix. the weaning center of our university hospital (post intensive care rehabilitation unit) admits for weaning and rehabilitation patients from medical and surgical intensive care units without severe neurological pathologies. the aim of this study was to describe patient's characteristics and outcome (weaning outcomes and survival) and to compare in subgroups according to the initial medical, surgical or cardiac surgical context. patients and methods: we conducted a monocentric retrospective observational study between / / and / / . «successful outcome» was defined by the association of survival and weaning from invasive ventilation. factors associated with evolution were investigated by uni-and multivariate analysis. survival after discharge was analysed according to the initial context and according to the type of ventilation at discharge. results: among patients included, ( . %) had a successful outcome with high use of non-invasive ventilation (niv) ( %). respiratory history (p = . ), female gender (p < . ), igs score at admission to the srpr (p = . ) and non-cardiac surgical setting (p < . ) were associated with an adverse course. the -month survival rate was % in discharged patients. the outcome was not different in the tree subgroups. niv rate at discharge was high in the subgroup of cardiac surgery patients. a multidisciplinary and personalised approach by a specialized weaning unit can provide a successful service model for patients who require liberation from prolonged invasive mechanical ventilation. compliance with ethics regulations: yes. rationale: high-dose insulin euglycemic therapy (hiet) is recommended as first line therapy for calcium channel blockers (ccbs) poisoning because of its inotropic effect. our first objective was to study its hemodynamic impact. we performed a retrospective cohort study of all consecutive patients admitted for ccbs poisoning treated with hiet, in one icu at the university hospital of lille between january and july . the hemodynamic impact was studied through mean arterial pressure (map), vasoactive-inotropic score (vis) and map/vis ratio during the h following hiet initiation. metabolic parameters were also collected. results: patients admitted for ccbs poisoning. patients treated with hiet in icu ( patients without circulatory shock, patients with shock after hiet and patients with shock at baseline before hiet). among shocked patients at baseline (n = ), no hemodynamic improvement was found except an increased map/vis ratio at h (p < . ). on the contrary, an initial worsening of vis ( [ rationale: ketamine is used in the induction and maintenance of general anesthesia. recently, there were concerns regarding its liver toxicity. we conducted a study to investigate the link between ketamine use and liver dysfunction (ld) in intensive care unit (icu) patients. patients and methods: data were extracted from the [anonymized] study, a randomized controlled trial designed to evaluate the effect of cisatracurium on -day mortality rate in moderate and severe acute respiratory distress syndrome (ards) patients. the main endpoint was the occurrence of a ld defined as a total serum bilirubin superior or equal to micromol/l. a matched case-control cohort was created: cases, receiving at least day of continuous ketamine infusion, were paired for with controls according to treatment with cisatracurium, hepatic and cardiovascular sofa sub-score, total serum bilirubin level at the time of inclusion, age, sex, ards from septic origin, shock anytime after inclusion. an analysis was also made on the whole cohort comparing the patients receiving at least day of continuous ketamine infusion to all patients who did not fulfill this criterion. results: cases were identified and matched to controls. in the ketamine group, the median ketamine duration was ( - ) days, and median total cumulative dose . ( . - . ) g. the occurrence of ld was higher in the ketamine group than in the matched control group ( . % versus . %, p = . , fig. ). the hazard ratio (hr) for ld in the ketamine group was . ( % ci . - . , p = . ). there was an increased risk of ld of . % per day of exposure to ketamine (hr . , % ci . - . p = . ) and of . % per gram of ketamine infused (hr . , % ci . - . , p = . ), with a risk starting to be statistically significant after days and gr. in multivariate analysis on the whole cohort, ketamine exposure (hr . , % ci . - . , p = . ), cumulative dose in gram (hr: . , % ic: . - . , p = . ) and ketamine exposure in days (hr: . , % ic: . - . , p < . ) remained independent risk factors for ld occurrence. conclusion: ketamine use in critically ill patients treated for ards is associated to a higher risk of liver dysfunction, assessed by total serum bilirubin. this risk is dose-dependent and increases with duration of treatment. the prescription of high doses or prolonged treatment with ketamine should probably be avoided in critically ill patients. compliance with ethics regulations: yes. rationale: ciguatera is one of the most common cases of marine poisoning associated with fish consumption in the world. the incidence of this intoxication is largely unreported. in martinique, the incidence of this intoxication seems constantly increasing. during the last years, numerous cases of large collective poisonings have been reported in martinique, especially during summer. the spectrum of clinical manifestations is large including gastrointestinal, neurological andcardiovascular symptoms. ciguatoxin, the toxin responsible for ciguatera fish poisoning is considered as a sodium channel agonist with cholinergic and adrenergic activity. it is rarely fatal and management of poisoned patients is essentially based on supportive care. the objective of this study was to describe the clinical characteristics and complications of ciguatera poisoning in martinique, focusing on the cardiovascular ones. observational, retrospective, single-center study covering six-year period from october to september , including all patients admitted to the emergency department of the university hospital of martinique (chu), and all patients who were declared to the regional health agency (ars) for ciguatera intoxication. results: one hundred and forty-nine patients ( ) who were ciguatera-affected were included. the incidence rate found was to be . cases per . patient-years in martinique over the period. about % of patients had gastrointestinal symptoms such as nausea, vomiting, diarrhea, or abdominal pain; % neurological disorders and % cardiovascular symptoms including, bradycardia, hypotension and interventricular block. ingestion of carangue fish was related to a major risk of chronic signs. conclusion: the incidence of ciguatera in martinique is increasing, with . cases/ . patient-years. the clinical presentation is defined mainly by digestive signs, followed by peripheral neurological disorders and cardiovascular symptoms. ciguatera fish poisoning in martinique presents similar clinical presentation to that of the other caribbean islands. there is no specific treatment. acute ciguatera poisoning is responsible for significant cardiovascular complications. physicians should be aware of the potential cardiovascular risk of ciguatera poisoning. compliance with ethics regulations: yes. rationale: pesticides have represented the most incriminated products in severe acute poisonings, in the developing countries, due to the availability of these products. organophosphate poisoning accounts for million poisonings/year worldwide. organophosphate (op) pesticides are used mainly as insecticides in agriculture. the moroccan anti-poison and pharmacovigilance centrer shows that op poisoning are responsible for % of all poisonings combined. the aim of our study: epidemiological, clinical, management and prognostic factors. patients and methods: a retrospective study was conducted on patients with op poisoning admitted to our nine-bed medical intensive care unit between january and december . inclusion criteria were: all patients over years of age and the exlusion criteria were: pesticide poisoning other than op, alcohol poisoning, drug poisoning, scorpionic poisoning and snake bites. statistical analysis was performed with spss software. results: forty patients were admitted for acute op poisoning. in morocco, organophosphores are available over-the-counter in several forms: rodentocides, malathion, cockroach trap, baygon insecticide ( fig. ). the average age was years with a female prévalence of . %. the intoxications were mostly intentional ( %). the symptomatology was determined by the three syndromes: central syndrome in %, muscarinic syndrome in %, nicotinic syndrome in %. rhythm disorders in %, and cardiovascular collapse in %. the symptomatic treatment was applied to all patients, antidotic treatment was administered in % of patients. the average length of hospitalization was days. conclusion: acute op poisoning is a real public health problem. its associated symptomatic treatment (respiratory and neurological resuscitation) and antidotic treatment. the mortality remains high in our context, therefore, we must attach great importance to the prevention. compliance with ethics regulations: yes. ( ). over an -month period, health officials in guadeloupe and martinique reported more than . such cases. assault of these brown algae represents not only an environmental and economic disaster, but also a threat for human health. after h on seashore, large amounts of toxic gas are produced by matter decomposition, including hydrogen sulfide (h s) and ammoniac (nh ). the acute effects on humans after exposure to high concentrations of h s are well described and of increasing severity with concentration, leading to potentially fatal hypoxic pulmonary, neurological and cardiovascular injuries (table ) ; however, the association of long-term exposure to sargassum and health events is unknown. although less documented, long term exposures may result in conjunctiva and upper airways irritation, headaches, vestibular syndrome, memory loss, and modification of learning abilities. in the absence of any available antidote, management of h s intoxication relies on supportive care and prevention using individual protection. the objective of this study was to evaluate the clinical characteristics and consequences of long-term exposure to sargassum among the local population. we conducted a prospective observational cohort study including all patients admitted to the emergency department at the university hospital of martinique from march to december due to exposure to sargassum. patients were managed according to the protocol established by the research group on sargassum in martinique. we assessed the patients exposure to sargassum and air pollutants using monitor located near of the patient's residence. demographics and clinical data (including cardiovascular, neurological and respiratory events) were collected. data are presented as mean ± sd or %.comparisons were performed using univariate analysis. results: in months, patients were included (age: ± years, m/ w, past history: hypertension (n = ), diabetes (n = ), asthma ( ). patients arrived with referral letter from their general practitioner ( %) and presented headaches ( %), developed gastrointestinal disturbances ( %), dizziness ( %), skin lesions ( %), cough ( %) and conjunctivitis ( %). not all patients were clinically symptomatic. in the patients presented in june ( %), symptoms more frequently occurred in the workplace or at home (p < . ). initial lung function tests were normal ( %). three patients were admitted in intensive care unit. conclusion: our study indicates that the magnitude of health effects following long-term exposure to sargassum may be larger than previously recognized. efforts to limit long-term exposure are mandatory. compliance with ethics regulations: yes. rationale: liver consequences of out-of-hospital cardiac arrest (ohca) have been poorly studied. the aim of this study was to describe the characteristics of ohca-induced acute liver dysfunction and its association with outcomes. we analyzed all consecutive ohca patients admitted to two academic centers between and . patients treated with vitamin k antagonist were not included. acute hepatocellular insufficiency (ahi), liver failure (lf) and hypoxic hepatitis (hh) were defined as a prothrombin (pt) ratio < %, a hepatic sofa sub-score > and an increase in transaminases > times the normal values, respectively. indocyanine green (icg) clearance was used as the reference measure of liver function in a subset of patients. multivariate logistic regression was used to identify potential risk factors for day mortality. rationale: neuron-specific-enolase (nse) is commonly used as a biomarker reflecting the extent of brain injury in different settings. in post-cardiac arrest patients, previous clinical studies reported that an increase in nse was predictive of a poor outcome but did not specifically focused on neurological outcome. in this prospective study, we aimed to determine the nse performance for prediction of severe brain damage in post-cardiac arrest patients. patients and methods: all consecutive patients admitted in our icu after cardiac arrest between january and february that were still comatose at h and had at least one measurement of serum nse were included. blood samples for nse measurement were serially collected at (h ) and h (h ) after cardiac arrest and serum nse levels were measured within h. we used the following criteria for the definition of severe brain damage (primary endpoint): cerebral performance categories (cpc) or level at discharge, brain death or withdrawal of life-sustaining treatments (wlst) based on neurological status. we also assessed the predictive value of serum nse using allcause mortality as a secondary endpoint. results: during the study period, patients were available for the analysis. they were mostly male ( . %), with an age of . years. among these patients, ( . %) had a good neurologic outcome (cpc - ) and patients were classified as having a severe brain damage ( wlst based on neurological status, brain deaths and survivors with . in univariate analysis, patients with severe brain damage less frequently received bystander cpr, had longer duration of no-flow, less initial shockable rhythm, more post-resuscitation shock and higher nse values: mean at h were . versus . ; and . versus . at h (p < . ). nse levels at h and h were strong predictors of severe brain damage (auc of . and . respectively, figure ) and also predicted all-cause mortality (auc of . and . respectively). to predict severe brain damage with % specificity, best nse cutoff values at h and h were . and . µg/l, with a sensitivity of . and . % respectively. conclusion: a high serum nse measured at h and h after cardiac arrest accurately predicted severe brain damage with a high specificity. our results support the use of nse for neuroprognostication after cardiac arrest, in combination with other predictors. compliance with ethics regulations: yes. rationale: the psychological care of patients, their relatives and of healthcare workers is a major issue in the intensive care unit (icu). psychologists may provide emotional support during trying times. the intervention of a psychologist may alleviate long term mental health issues such as post-traumatic stress disorder. the main objective of our study was to describe the availability of psychologists in french-speaking icus. patients and methods: internet survey conducted between march and may using surveymonkey (san mateo, usa). survey consisting of questions sent to subscribers of the srlf mailing list via mailchimp software (atlanta, usa). frequencies and percentages were determined for categorical variables and median and interquartile range for continuous variables. the icus with or without psychologist were compared using nonparametric fisher exact test. stata used (lakeway drive, te, usa). results: responses were obtained from unique icus in france (n = ), belgium (n = ), switzerland (n = ), algeria (n = ), morocco (n = ) and tunisia (n = ). ( %) icus were part of public hospitals, ( %) of private facilities. ( %) icus cared for adult patients, ( %) for children. the median number of beds was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . ( %) icus were open to visitors / , ( %), to visitors > h/day and ( %) to visitors < h/day. psychological consults were established in ( %) wards ( icus did not answer). pediatric icus employed more psychologists than adult icus (p = . ). comparison of icus based on the presence or not of a psychologist appears in table . in icus where a consulting psychologist is available, their effective availability is . [ . - ] full time equivalent. consults are delivered to: patients ( %), families ( %) or healthcare workers ( %). out of the icus without a psychological consult, responders from ( . %) icus believe that a psychological consult is undesirable. out of the icus without psychological consult, ( %) responders cannot obtain a psychological consult, whatever the circumstances, ( %) can require an outside psychological consult when needed, while ( %) can require assistance from a psychologist working in another unit (several answers possible for each respondent). conclusion: psychologists consult in only half of adult icus but in almost all pediatric icus. % of icus are unable to provide a psychological consult. psychological consults are delivered in similar proportions to patients, their family and to a lesser extent to healthcare workers. responders from . % icus without an established psychological consult believe that the availability of a psychologist is undesirable. compliance with ethics regulations: na. rationale: comfort of patients in intensive care unit (icu) is now a real concern for the healthcare teams. perceived patient discomfort assessment is a daily practice for our staff. the primary objective of our study was to assess whether the overall discomfort score reported by patients hospitalized in a separate intermediate care unit differs from that reported by patients hospitalized in icu. a tailored multicomponent program consisting of assessment of icu-related self-perceived discomforts with a -item questionnaire, immediate and monthly feedback to healthcare teams and site-specific tailored interventions, was applied in our department, located in a general hospital, and comprising a -bed icu and a separate -bed intermediate care unit rationale: the transition period surrounding the discharge from icu to hospital ward is a critical period in the course of the patient. handoff of complex patients is at high risk for communication failures between providers, inaccurate cares and icu readmission. a transition program including a post icu follow-up has been proposed to improve handoff quality. post icu consults by icu team represent, also, an opportunity for improving feedback on the quality of icu cares. the goal of the present study is to assess the feasibility and the impact of a systematic early post-icu consult (epicuc) program on handoff quality in a bed mixed icu. patients and methods: before the development of the epicuc program, standardized handoffs were already applied including identified day and hour of discharge and both verbally communicate and written medical and nurse information for receiving team. from st march to th october , all patients who were discharged to the ward of our hospital were candidates for epicuc. epicuc were performed by icu staff (at least one icu physician) within the days following discharge. the epicuc consisted of a face-to-face discussion with the receiver team to assess the accuracy, completeness and understanding of passing information and of a patient visit. a standardized form was used for collecting data. the impact of epicuc on handoff quality was assessed by the number of communication failures and the number of patients in whom epicuc resulted in a management change. personal feeling of epicuc providers on its usefulness was assessed by a - rating scale. results: among the candidates for epicuc, were dead and already discharged alive from hospital at epicuc time. epicuc were performed in patients ( %) within ± days after icu discharge. epicuc ( %) were performed by both, nurse and icu physician. ( %) patients and receiver teams ( %) were available at epi-cuc time. epicuc duration was ± min. a communication failure was identified in epicuc ( %), either a rectification of passing information (n = ; %) and/or a change in patient management (n = ; %). the usefulness of the epicuc was rated at ± and ± by icu physicians and nurses, respectively. conclusion: the time spent for epicuc appears reasonable. epi-cuc identified a communication failure in one-third of handoffs and allowed care readjustment in one quarter of patients. factors associated with handoff failures will be presented during the congress. compliance with ethics regulations: yes. rationale: surviving a critical illness is a challenging condition for patients and relatives. the psychological aspects are directly affected by physical status and performance. patients can feel depressed or anxious facing difficulties during recovery time. the aim of this study was to correlate patients' perceptions of his health status and his clinical performance measured after icu discharge. patients and methods: this is a prospective pilot study of an icu follow-up clinic conducted in a single center from january to july . this clinic is multidisciplinary and includes two visits at and months after icu discharge. patients with more than days of icu los were eligible. all patients at and -m visit were evaluated with sf- , mwt, mrc and time-up-and-go test. we conducted an analysis comparing clinical performance data and qualitative data between and months after icu discharge. the investigation included patients who had at least days of icu length of stay. patients attended the consult at -m and patients attended the consult both times. the median age (iqr) was ( - ) and % were men. %, % and % of patients had medical, scheduled surgical and emergency surgical admission causes respectively, with median (iqr) saps iii score ( - ). %, % and % of patients had sepsis, delirium and mechanical ventilation as a support. the physical status was progressively increased overtime likewise the physical capacity assessed by sf- score with p-value . between and -m. however, no significant difference between the subjective dimension of sf- , which analyses the perception of the patient about his physical capacity, assessed at -m and at -m was demonstrated (p . ). in this pilot-phase of following a cohort of critically ill patients, the natural physical improvement does not seem to change the patient's perception of their performances. this paradigm rouses a different perspective that should take into account when setting up rehabilitation programs. compliance with ethics regulations: yes. post-traumatic stress disorder after discharge from an acute medical unit basma lahmer , naoufel madani , , jihane belayachi , , redouane abouqal rationale: post-traumatic stress disorder (ptsd) occurs after exposure to a traumatic event and comprises of symptoms of repeated re-experiencing of the said event, avoidance of reminders, emotional numbing and persistent hyperarousal. in individuals exposed to "medical stress", various studies found evidence of ptsd occurring after the onset, diagnosis, or treatment of physical illness. our study aims to determine ptsd's risk factors in patients of an acute medical unit (amu) after their discharge. patients and methods: it was a prospective, analytical study conducted over a period of months at an acute medical unit. we collected sociodemographic and clinical data, patients' medical history, and evaluated the symptoms of anxiety and depression during their stay using the hospital anxiety and depression scale (hads). the prevalence of severe ptsd symptoms was assessed with the impact of events scale-revised (ies-r) at weeks and months using a cutoff of . associations between ptsd as evaluated by ies-r at months and patients' characteristics, including hads scores at admission were investigated using unadjusted linear regression, for univariate and multivariate regression analysis. statistical analyses were carried out using spss for windows (spss, inc., chicago, il, usa). we included patients in our study with a mean age of . ± . . in our population, . % of patients scored higher than a ies-r cutoff at weeks compared to . % at months. the mean hads-anxiety score is . ± and that of the hads-depression score is . ± . . on one hand, higher hads-anxiety score during the stay in the amu was linked to higher ies-r scores at months β: rationale: objective of critical care includes restoration of functional capacities. prompt identification of muscle acquired weakness (icu-aw) is crucial to target efficient rehabilitation. in published literature, data of quadriceps strength (qs) cannot be compared because of insufficient standardization of measurement protocols. we recently validated a highly standardized protocol of qs measurement. in order to build basic and comparable knowledge and to identify the weakest patients, this study aimed to describe qs of critically ill (ci) patients during their short-term evolution, and to compare them to surgical (s) and healthy (h) subjects. patients and methods: this observational study included ci patients who spent at least days in icu, patients scheduled for elective colorectal surgery (s) and young healthy volunteers (h). maximal isometric qs was assessed using a handheld dynamometer (microfet ® ) and expressed in newton/kg (n/kg). dominant leg was tested in supine position using a highly standardized procedure. ci and s patients were tested at t (as soon as collaborative in icu) and month after discharge (m rationale: the post intensive care syndrome (pics) gathers various disabilities, associated with a substantial healthcare use. however, patients' comorbidities and active medical conditions prior to intensive care unit (icu) admission may partly drive healthcare use after icu discharge. to delineate the relative contribution of critical illness and pics per se to post-critical illness increased healthcare use, as opposed to pre-existing comorbidities, we conducted a population-based evaluation of patients' healthcare use trajectories. patients and methods: using discharge databases in a . -million-people region in france, we retrieved, over three years, all adult patients admitted in icu for septic shock or acute respiratory distress syndrome (ards), intubated at least days and discharged alive from hospital. healthcare use (days spent in healthcare facilities) was analyzed two years before and two years after icu admission. healthcare trajectories were next explored at individual level: patients were assembled according to their individual pre-icu healthcare use trajectory by clusterization with the k-means method. results: eight-hundred and eighty-two ( ) patients were included. median duration of mechanical ventilation was days (interquartile ranges [iqr] ; ), mean saps was , and median hospital length of stay was days (iqr ; ). prior to icu admission, we observed, at the scale of the whole study population, a progressive increase in healthcare use. however, clusterization of individual according to pre-icu healthcare trajectories identified patients with elevated and increasing healthcare use (n = ), and two main groups with low (n = ) or no (n = ) pre-icu healthcare use. patients with high healthcare use had significantly more comorbidities than those with low healthcare use. in icu, however, saps , duration of mechanical ventilation and length of stay were not different across the groups. interestingly, analysis of post-icu healthcare trajectories for each group revealed that patients with low or no pre-icu healthcare (which represented % of the population) switched to a persistent and elevated healthcare use during the two years post-icu. conclusion: for % of ards/septic shock survivors, critical illness appears to have a pivotal role in healthcare trajectories, with a switch from a low and stable healthcare use prior to icu, to a sustained higher healthcare recourse two-years after icu discharge. this underpins the hypothesis of long-term critical illness and pics-related quantifiable consequences in healthcare use, measurable at a population level. compliance with ethics regulations: yes. ( ) to describe the pre-hospital grading protocol developed by the northern french alps emergency network (trenau) for children, ( ) to evaluate its quality to detect the most severe trauma patients and ( ) to assess the accuracy of this procedure to perform an adequate triage. patients and methods: our regional trauma system included hospitals categorized as level i, ii or iii pediatric trauma centers. eachpatient was graded a, b or c by an emergency physician, according to the seriousness of their injuries at presentation on scene. the triage was performed according to this grading and the categorization of centers. this study is a registry analysis of an -year period ( to ). results: a total of children (mean age years, % were boys) with severe trauma were included in the cohort. fifty-seven, % and % of patients were admitted to a level i, ii and iii, respectively. road accident was the main mechanism of injury ( % of patients). thirtysix percent of patients had a severe trauma, defined as an injury severity score (iss) higher than . one quarter of patients had at least severe lesions and one-third of patients had a trauma brain injury. the pre-hospital gradation was closely related with injury severity score (iss) and intra-hospital mortality rate. the triage protocol had a sensitivity of % and a specificity of % to predict adequate admission of patients with iss more than . using a specific trauma score (including occurrence of death, an admission in intensive care unit and the need for urgent surgery), sensitivity and specificity reached and %, respectively. fourty-six percent of patients were not graded at the scene (non-graded group). undertriage rate was significantly reduced in the graded group compared with the non-graded group, ( % versus %), without significant modification of the overtriage rate ( % versus %). overall, mortality at discharge from hospital was %, but % in grade a patients. conclusion: implementation of a regional pediatric trauma system with a specific pre-hospital triage procedure was effective in detecting severe pediatric trauma patients and in lowering the rate of prehospital undertriage. compliance with ethics regulations: yes. rationale: critically ill children suffer from pathophysiological changes, leading to large between-subject variability in drug clearance. since piperacillin is eliminated mainly via the kidney, changes in renal function go along with a modified elimination, and possible subtherapeutic or toxic drug concentrations. we aimed to determine the most accurate glomerular filtration rate (gfr) estimation formula for assessing piperacillin clearance in critically-ill children. patients and methods: all children hospitalized in pediatric intensive care unit and receiving piperacillin were included. piperacillin was quantified by high performance liquid chromatography. pharmacokinetics were described using the non-linear mixed effect modeling software monolix. in the initial pharmacokinetics model, gfr was estimated according to the schwartz formula. in the study, gfr was estimated with additional formulas, developed with plasma creatinine and/or cystatin c. biases, precisions, spearman's rank correlation coefficient and normalized prediction distribution error (npde) were used to assess the models. results: we included children with a median (range) postnatal age of . ( . - ) years, body weight of . ( . - ) kg and estimated gfr according to the schwartz formula of . ( - ) ml min- . . m . piperacillin concentrations were best predicted with the model using the creatinine clearance. the correlations were most accurate: r = . between the population-predicted and the observed concentrations, r = . and r = . for the npde versus population-predicted concentrations and time, respectively. concerning the individual predicted concentrations, bias and precision were respectively − . mg l − and . mg l − . gfr estimations based on serum creatinine were higher than those based on cystatin c (p = . ). conclusion: in summary, the -h creatinine clearance is the best predictor of piperacillin clearance and this could be investigated for drugs with renal elimination. as a whole, literature and our findings strongly suggest using creatinine clearance to also estimate gfr in critically ill children. the gap between the gfr estimations is large depending on the formulas, with higher estimations with equations based on serum creatinine. compliance with ethics regulations: yes. rationale: acute pancreatitis (ap) incidence have increased dramatically over the past years. new guidelines in were recently published in order to standardize the definition and management of ap. the aim of this study is to describe the management of children that were diagnosed with ap from the pediatric intensive care unit (picu) in two french hospitals. patients and methods: this retrospective cohort study included children aged under years old, who were admitted to the picu of robert-debré hospital and trousseau from to with a discharge diagnosis of ap. data collected included management, severity and outcomes. we have also obtained data on clinical, biological and radiological presentation. results: sixty patients were included, the median age was years ( - ) and % had a co-morbidity mainly hematologic ( / ). most of the ap were moderate ( %) or severe ( %). hemodynamic failure was the main reason for picu admission requiring a median fluid resuscitation ml/kg complemented by a median intravenous fluid therapy of ml/kg/h ( - ) during the first h. twenty patients ( %) required mechanical ventilation. fasting has been instituted in patients ( %) for a median of days ( - ), whereas patients ( %) received parenteral nutrition, only patients ( %) received enteral nutrition. antibiotic therapy was given to patients ( %) including % for curative therapy. the median length of stay in picu was days ( ) ( ) ( ) ( ) ( ) . the mortality rate was %. conclusion: this is the first french study which precisely described the management of patients with ap in picu. it highlighted the differences withthe new international guidelines. this study could improve the management of pa in picu and open research perspectives. compliance with ethics regulations: yes. rationale: apheresis and therapeutic plasma exchange (tpe) for children diseases has been poorly investigated in mostly small-uncontrolled studies. the purpose of this study is to describe indications and safety of tpe in children. patients and methods: in this single center and retrospective study, we included patients who underwent tpe with an age < years old in the pediatric center of necker-enfants-malades hospital from january to december . data were retrospectively collected in an electronic case report form via a web-based data collection system. results: patients with a median age of . years [range . ; . ] were selected. they achieved a total number of procedures. indications were antibody-mediated rejection (n = ; %) or desensitization therapy (n = ; %) for solid organ or hematopoietic transplantations; microangiopathy (n = ; %); renal diseases (n = ; %) and pediatric inflammatory diseases (n = ; %); or hyperviscosity syndrome (n = ; %). each patient had an average of procedures for the first session [range ; ] with a median volume of ml [range ; ml] corresponding to a median (rang) total plasma volume (tpv) equivalent of . l/m [ . - . ]. within days since the beginning of sessions, patients ( %) present a total of adverse events (aes) potentially related to tpe. there was a median (range) of aes/patients [ - ]. there was no association between aes and diseases, severity of patients, venous access, plasma substitute and body weight. few of aes (n = for patients) were potentially life-threatening and concerned mostly critically ill children. allergic reactions represented only aes for patients (grade i n = ; grade ii n = ; grade iii n = ). at the months endpoint, ( %) patients died and ( %) patients had severe persistent disease. no death had been related to the tpe process. we describe one of the largest retrospective pediatric cohort updated to the last international recommendations. tpe in children is performed for specific and potentially refractory disease. it is feasible without a major risk of life threatening adverse events. compliance with ethics regulations: yes. yacine benhocine university hospital nedir mohamed, tizi-ouzou, algeria correspondence: yacine benhocine (yacine @yahoo.fr) ann. intensive care , (suppl ):f- rationale: although analysis of literature data shows that implantable chamber catheters (iccs) are less at risk of infectious complications than other central venous catheters, these complications can be serious, which may differ from ongoing treatments such as chemotherapy, and may lead to the removal of the implanted device. the literature on preventing these infections is quite disparate, as practices. purpose: to evaluate the incidence of infections, to identify responsible germs and to measure the impact of preventive measures. patients and methods: prospective, descriptive, mono-centric study, from january to january . all patients under the age of who have benefited from an implantable chamber catheter, whose insertion procedure is as follows: local anesthesia, surgical asepsis (polyvidone iodine) in an operating room, double disinfection, no antibiotic prophylaxis, routes used: subclavian ( %), internal jugular ( %) by anatomic registration. the main criteria of judgment are: the incidence of local and general infections, their time of onset, responsible microorganisms. statistical analysis used the statistical package for the social sciences software. results: patients were included, the average incidence density of early infection is . / day-catheters. the time of onset of infection is essentially between the nd and rd week post-exposure, of which % is general infection. ablation involved % of infected catheters. the causative organisms are mainly gram-positive cocci ( . %), gram-negative bacilli are less involved ( . %), with a significant number of candida infections ( %). discussion: higher incidence of data from the literature. to remedy this requires the implementation of additional hygiene measures: antiseptic showers preoperatively, chlorhexidine??, and practice changes: echo guidance, antibiotic prophylaxis or locks? second generation catheters? our practices are disparate especially since the recommendations specifically concerning the prevention of infectious risk associated with internationally published iccs are rare. conclusion: at the end of this work, our perspectives are to: update the procedure, highlight risk factors on which it is possible to act, the adhesion of the different staff to the protocols. compliance with ethics regulations: yes. rationale: the sepsis and septic shock pediatric guidelines advise to treat patients using care bundles. in the first hour, the «resuscitation bundle» contains an appropriate fluid resuscitation, a broad-spectrum antibiotics administration after blood cultures, and initiation of inotrope if needed. the objectives were to evaluate the resuscitation bundle compliance in a cohort of septic children with cardiovascular dysfunction, and to analyze the effect on severity and outcome in pediatric intensive care unit (picu). patients and methods: retrospective analysis of the diabact iii study. this study analyzed the care course of children with severe community-acquired bacterial infection, hospitalized in picus in france's west departments, between august and january . children with severe sepsis and cardiovascular dysfunction were retrospectively included. results: we included children of whom ( . %) had compliant bundled care. the severity scores at picu's admission were similar between groups (p = . for the prism score and . for the pelod ). there was the same proportion of fluid-refractory shock (p = . ), mechanical ventilation (p = . ), neurological dysfunction (p = . ) and cardiac arrest (p = . ). in the «resuscitation bundle compliant» group, . % died versus . % in the other group (p = . ). we highlighted a severity bias: the sickest patients were more likely to receive compliant bundled care. conclusion: in our cohort, the resuscitation bundle's compliance was low. we did not show some effect on morbidity nor mortality. however, this study helps understand the factors associated with resuscitation bundle's compliance. rationale: nosocomial infections with extended-spectrum β-lactamase (esbl) producing gram-negative bacilli (gnb) are an important cause of hospital morbidity and mortality. the objective of this study was to determine the incidence and risk factors of nosocomial esbl-producing gnb infections in a paediatric intensive care unit (picu). patients and methods: a prospective surveillance study was performed from january through march in a picu. all patients hospitalized for more than h were included. centers for disease control and prevention criteria were applied for the diagnosis of nosocomial infection. results: during the study period, patients (median age: ± days) were included. the average length of stay was ± days with a total of , days of hospitalization. newborns accounted for . % of patients. sixty-two per cent of patients were colonized with multi drug resistant gram-negative rods, on admission or during their stay in the picu. one hundred and nineteen bacterial infectious episodes were registered ( . / patient days). one hundred infectious episodes were caused by a gnb and ( . %) by esbls producing gnb with an incidence of . / patient days (bloodstream infections: episodes, ventilator acquired pneumonia: episodes). esbls producing gnb infection had a specific incidence of . per catheter-days, and . per mechanical ventilation-days. fifty-nine percent of patients infected with esbls producing gnb had a prior digestive colonization with a multidrug-resistant gnb. forty-one episodes ( %) occurred in patients with central venous catheters. klebsiella pneumoniae was the most frequently isolated bacteria ( . %). mortality in the esbls producing gnb group was high ( . %). associated factors of nosocomial esbls producing gnb infection were mechanical vrntilation (p < . ), central venous catheterization (p < . ) and colonization with multiple drug-resistant gram-negative bacteria (p < . ). conclusion: nosocomial esbl-producing gnb infection had an incidence of . per patient days in our unit and seems to increase the mortality rate. factors associated with this infection were identified. marie lemerle , aline schmidt , valérie thepot-seegers , achille kouatchet , valérie moal , mélina raimbault , corentin orvain , jean-francois augusto , julien demiselle chu angers, médecine intensive réanimation, angers, france; chu angers, maladie du sang, angers, france; chu angers-ico, angers, france; chu angers, pharmacie, angers, france; chu angers, labora-toire de biochimie, angers, france; chu angers, néphrologie dialyse transplantation, angers, france correspondence: marie lemerle (marielemerle@yahoo.fr) ann. intensive care , (suppl ):f- rationale: acute kidney injury (aki) is associated with high morbidity and mortality in the setting of tumor lysis syndrome (tls). thus, strategies aimed at preventing aki occurrence represent a major goal to improve prognosis of patients with tls. the role of hyperphosphatemia as a risk factor of tls has been poorly analyzed. the aim of this study was to study the association between hyperphosphatemia and aki, and to determine whether a cut-off value of phosphatemia or phosphatemia's variation was associated with aki development during tls. patients and methods: in this retrospective and monocentric study, we included all patients with tls and whithout aki at admission, admitted to hematology, nephrology and intensive care units of the university hospital of angers between / / and / / . results: one hundred and thirty tls episodes were identified in patients. aki developed during episodes of tls ( %). hospital mortality was much higher in aki patients ( . % versus . %, p = . ). phosphate maximal values ( . ± . versus . ± . ) and ldh maximal values ( . ± . versus . ± . ) were higher in tls with aki, before aki occurrence (p = . and p = . , respectively). we found no association between the other biological parameters of tls and aki (serum calcium, uric acid and potassium). after adjustment for cofounders, there was a strong association between a rise in phosphate level of . mmol/l (hr . ic % [ . - . ], p < . ), exposure to platinum salts (hr . ic % [ . - . ], p = . ) and increasing maximal ldh value (hr per ui/l increase . ic % [ . - . ], p = . ) with aki. conclusion: this study highlights the utmost importance of serum phosphate in the setting of tls: phosphate is an early relevant biomarker for the risk of aki development. further studies are needed to assess whether aggressive prophylactic treatment to control serum phosphate concentration, such as renal replacement therapy before aki onset, constitutes a valuable approach. compliance with ethics regulations: yes. retrospective cohort of patients admitted to the medical icu of university affiliated hospital after carts treatment between august and august . results: of the patients treated by carts in the haematology department, ( %) were subsequently admitted to icu. median age was [ . - . ] years, and ( . %) were female. carts were indicated for r/r lymphoma. the median time between carts injection and icu admission was [ . - . ] days. all patients had cytokine release syndrome (crs), and ( . %) developed car-related encephalopathy syndrome (cres). median sofa score and saps were [ - . ] and [ . - . ], respectively. four ( . %) patients had hypotension treated by fluid bolus (n = ) or vasopressors (n = ), and ( . %) had acuterespiratory failure requiring oxygen therapy (n = ) or mechanical ventilation (n = ). six ( . %) patients had neurological symptoms (impaired consciousness n = , confusion n = , transient aphasia n = ), of whom one developed refractory convulsive status epilepticus afterwards. all patients received broad spectrum antibiotics, of whom ( . %) had documented infections. six ( . %) patients received interleukin- inhibitor (single dose n = , multiple doses n = ), and ( . %) received intravenous dexamethasone. one patient died in the icu from septic shock. median icu and hospital length of stays were [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and [ . - . ] days, respectively. two ( . %) patients died from relapsing malignancy before hospital discharge. three months after icu admission, four ( . %) patients were alive in complete remission. conclusion: more than % of patients treated with carts required icu admission for the management of a crs or a cres. early icu admission, close collaboration between haematologists and intensivists, and prompt administration of appropriate therapy (il- inhibitor and/or dexamethasone) and supportive care resulted in a good prognosis. compliance with ethics regulations: yes. rationale: tisagenlecleucel (ctl ) is a chimeric antigen receptor t cell therapy that reprograms autologous t cells to target cd + leukemia cells, approved in the us since august and in the eu since august for children and young adult (< years old) with relapsed/refractory b-cell acute lymphoblastic leukemia (b-all). this study reports the experience of picu management of ctl toxicity in patients treated in robert-debré university hospitals. patients and methods: all patients (age < years old) treated by tisagenlecleucel infusions between march , and september , , included in sponsored-clinical trials or treated within the french compassionate program or with the commercial product, were retrospectively analyzed. results: twenty-four patients were infused and patients ( %) were managed in picu for stays. ( stays: n = and stays: n = ). median age at picu admission was . years old [ . ; . ] with a median delay after car-t cells infusions of days [ . ; ] . the median length of stay in picu was days [ . ; ] with a max at days. cytokine release syndrome (crs) was the main indication of picu hospitalization ( . %, n = ) with grade (n = ) and grade (n = ) according to american society for transplantation and cellular therapy (astct) consensus grading system and treated by corticosteroid (n = . ) and tocilizumab (n = , only one infusion). norepinephrine was the only vasopressor used. the median vaso-inotrope score (vis) for grade was [ . ; . ] with a maximum at . neurologic toxicity was observed in patients with a grade (status epilepticus) and grade (focal edema on neuroimaging with depressed level of consciousness) according to immune effector cell-associated neurotoxicity syndrome (icans) grading system from astct consensus. the status epilepticus was managed with anti-epileptic drugs without mechanical ventilation. the focal edema was related to hhv and toxoplasmosis encephalitis. evolution was positive with foscavir and ganciclovir and days of mechanical ventilation. one patient was hospitalized for septic shock secondary to gram-negative central line bloodstream infection in aplasia, with a vis score at . evolution was favorable with antibiotics and central line removal. no death in picu from severe tisagenlecleucel toxicity was observed since the beginning of the car-t cells program. conclusion: toxicity profile of tisagenlecleucel required frequent and early picu hospitalization after infusions for severe crs and icans management. compliance with ethics regulations: yes. rationale: car-t cell (chimeric antigen receptor t) therapy is a promising treatment in refractory acute lymphoid leukemia (all) and diffuse large b cell lymphoma (dlbcl). the main complication consists in a cytokine release syndrome (crs) leading to an inflammatory state that can be very severe with life-threatening organ failure. neurological toxicity is also reported. we aim to describe car-t cells-related complications in icu patients. patients and methods: this is a single-center prospective study conducted between july and august . all the patients who have received car-t cells and who required icu admission were included. crs grading was defined according to the most recent classification of the asbmt and neurological toxicity was assessed with the cartox scale. each admission is considered independent and therefore corresponds to one patient. results: admissions, representing patients ( men and women), were considered. the median age was years . twothirds of the patients have been diagnosed with dlbcl (n = , %) and one-third with all (n = , %), months [ - ] ago. they had received lines [ ] [ ] of chemotherapy and had a high tumor burden ( % of lymphomas classified stage iv). the majority of the patients was admitted because of hemodynamic failure (n = , %) or respiratory failure (n = , %), days [ ] [ ] [ ] [ ] [ ] after car-t cells infusion. sofa at admission was [ ] [ ] [ ] [ ] [ ] . all the patients presented at least one complication ( figure) , the most common being crs (n = , %) with a median grade of [ ] [ ] . neurological toxicity was reported in ( %) patients (worst grade at [ ] [ ] [ ] ). documented bacterial infection involved % of the patients and consisted in catheter-related infections for half of the cases. in the icu patients were managed with fluid resuscitation (n = , %) during the first day, vasopressors (n = , %) and broad spectrum antibiotics ( %). a single patient required mechanical ventilation and two patients underwent dialysis. tocilizumab (anti-il receptor) was given to patients ( % of crs) in a median time of . h [ . - . ] after icu admission. patients ( %) received corticosteroids. the median icu length of stay was . days [ ] [ ] [ ] [ ] . patients ( %) died in the icu and hospital mortality was %. the -fluorouracil ( -fu)-induced hyperammonemic encephalopathy is a rare but serious -fu adverse drug reaction, which could require the admission of patients in intensive care unit (icu). given the paucity of data regarding this -fu adverse drug reaction, we performed a retrospective national survey from the french pharmacovigilance database to better characterize -fu-induced hyperammonemic encephalopathy and its management. patients and methods: since the inception of the french pharmacovigilance database, we identified all patients that experienced -fu-induced encephalopathy. variables regarding epidemiology, characteristics, management and prognosis of these patients were collected and analyzed. results: from from to years-old, % of women) were included. overall mortality was % (n = ) and % (n = ) of patients were admitted in icu. the -fu-induced hyperammonemic encephalopathy started [ ] [ ] [ ] [ ] days after the onset of -fu infusion. the most common neurological disorders were consciousness impairment, confusion and seizures. abnormalities in ct scan, mri, electroencephalogram and lumbar puncture were found in %, %, % and % of the whole population respectively, similar in icu and non-icu patients. ammonemia was dosed in % of the whole population and in % of icu patients. hyperammonemia tended to be higher in icu than in non-icu patients ( [ - ] vs. [ - ] µmol/l, respectively, p = ns) and in patients with the lowest glasgow outcome scale, but was not different between survivors and non-survivors. among icu patients, % required mechanical ventilation and % anti-epileptic drugs administration. besides -fu discontinuation, lactulose intake, renal replacement therapy or ammonium chelators were used to decrease hyperammonemia in %, % and % of patients respectively. a complete neurological recovery was observed in up to % of icu and non-icu patients within a delay of [ - ] days. a dihydropyrimidine deshydrogenase (dpd) deficiency was found in % of tested patients. a -fu rechallenge was considered in % (n = ) of patients with complete neurological recovery, including a patient with a partial dpd deficiency, within a delay of [ - ] days after recovery. a -fu-induced hyperammonemic encephalopathy relapse was observed in % of patients with -fu rechallenge. no relapse was observed when -fu rechallenge was performed with a decreased -fu dosage. conclusion: we report the first national survey and the largest cohort of patients with -fu-induced hyperammonemic encephalopathy so far. this serious -fu adverse drug reaction must be known by intensivists, since more than half of patients are admitted in icu and specific treatments are available. compliance with ethics regulations: yes. immune related adverse events: a retrospective look into the future of oncology in the intensive care unit adrien joseph , annabelle stoclin , antoine vieillard-baron , guillaume geri , jean-marie michot rationale: immune checkpoint inhibitors (ici) represent a paradigmatic shift in oncology. with their new position as a mainstay in cancer treatment, new toxicities called immune related adverse events (iraes) have emerged. patients and methods: retrospective study including patients admitted in the icu within days after treatment with an ici in french hospitals. patients were classified into groups according to the reason for admission: irae, intercurrent adverse event (intae) or event related to tumor progression (tumprog). results: patients were admitted during the course of an ici treatment, including irae, intae and tumprog, with a significant increase between (n = ) and (n = patients, p for trend < . ). irae included pneumonitis, colitis, diabetes complications, hypophysitis, nephritis, myocarditis and cardiac disorders, hepatitis or allergic reaction and meningitis. the immune related nature of the complication was known before admission in only ( %) cases. mean age was (± ) years and % had a performance status of - . primary tumors were melanomas ( , %), non-small cell lung cancers ( , %) , urothelial carcinomas ( , %) and hodgkin lymphomas ( , %) . ici at the time of admission included anti-ctla ( , %), anti-pd /pdl ( , %) and anti-ctla /anti-pd combination in ( %) patients. mean duration of stay in the icu was . (± ) days. three patients required vasopressor therapy alone, with mechanical ventilation and one with extracorporeal membrane oxygenation. three patients required non-invasive ventilation and renal replacement therapy alone. six required only endocrine or electrolytic equilibration and others did not receive any form of organ support. icu mortality was %. compared with other admissions, anti-ctla or anti-ctla /anti-pd combination treatments were associated with irae diagnosis (or = . [ . - . ] , p = . for anti-ctla and . [ . - . ] for anti-ctla /anti-pd , p = . ) and so was the diagnosis of melanoma ( . [ . - . ] , p = . ). there was no difference in terms of icu and post-icu survival between irae (median post-icu survival months [ -na]), intae ( . [ . -na]) and ). six patients admitted for an irae were rechallenged with the same ici after icu discharge and achieved complete response. conclusion: we conducted the first study describing patients admitted in the icu for iraes. their specific and heterogeneous profile, along with the expected increase in the number of admissions, underlines the need for an in-depth knowledge for icu physicians in order to take part in the multidisciplinary care required by these patients. compliance with ethics regulations: yes. rationale: patients with advanced-stage non-small-cell lung cancer have high mortality rates in the intensive care unit (icu). in this context, acute respiratory failure due to cancer involvement is the worst situation. in the last two decades, targeted therapies have changed the prognostic of patients with lung cancer outside the icu. unlike cytotoxic chemotherapy, the fast efficacy of targeted therapies led some intensivists to use them as rescue therapy for icu patients. we sought to investigate the outcomes of patients with lung cancer involvement responsible for acute respiratory failure and who received tyrosine kinase inhibitor during icu stay. patients and methods: we performed a national multicentric retrospective study with the participation of the grrroh (groupe de recherche en réanimation respiratoire en onco-hématologie). all patients with non-small-cell lung cancer admitted to the icu for acute respiratory failure between and were included in the study if a tyrosine kinase inhibitor was initiated during icu stay. cases were identified using hospital-pharmacies records. we collected demographic and clinical data in icu charts. vital status was assessed at the time of study completion (august ). the primary outcome was overall survival days after icu admission. results: twenty-nine patients (age: ± years old) admitted to a total of icus throughout france were included. seventeen patients ( %) were nonsmoker. the most frequent histological type was adenocarcinoma (n = , %) and a majority had metastatic cancer (n = , %). epithelial growth factor receptor mutation was the most common oncologic driver identified (n = , %). during the icu stay, ( %) patients required invasive mechanical ventilation, ( %) catecholamine infusion, ( %) renal replacement therapy and one ( %) extracorporeal membrane oxygenation. in addition to tyrosine kinase inhibitor, ( %) patients received steroids (beyond . mg/kg/day) and ( %) cytotoxic chemotherapy during icu stay. seventeen patients ( %) were discharged alive from icu and ( %) were still alive after days (see kaplan-meier curve figure) . moreover, patients ( %) were alive one year after icu discharge. conclusion: despite a small sample size this study showed that, in the context of lung cancer involvement responsible for acute respiratory failure, the use of tyrosine kinase inhibitor should not be refrained in patients with severe condition in icu. compliance with ethics regulations: yes. rationale: acute respiratory failure is the leading reason for intensive care unit (icu) admission in immunocompromised patients and the need for invasive mechanical ventilation has become a major clinical end-point in randomized controlled trials (rct). however, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. this study explores how this outcome varies across icus. patients and methods: hierarchical models and permutation procedures for testing multiple random effects were applied on both data from observational cohort (the trial-oh study: patients, icus) and randomized controlled trial (the high trial: patients, icus) to characterize icu variation in intubation risk across centers. results: the crude intubation rate varied across icus from % to % in the observational cohort and from to % in the rct. this center effect on the mean icu intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p-value = . , median or . [ . - . ]; rct: p-value: . , median or . [ . - . ]). two icu-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to icu admission) and could partly explain this center effect. in the rct that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. conclusion: invasive mechanical ventilation has become an important endpoint in immunocompromised patients with acute respiratory failure. however, we found significant variation in intubation risk across icu in both an observational cohort and a randomized controlled trial. our results highlight the need to take into account center effect in analysis because it could be an important confounder. reasons for heterogeneity are various (case-mix differences, center practices). this gives opportunities to future improvement in care management and study design. compliance with ethics regulations: yes. rationale: influenza virus (iv) infection is a major cause of ards that has been the focus of attention since the pandemic h n (h n pdm ) iv. although iv-mediated damage of the airway has beenextensively studied emphasizing specificity compared to other causes of ards, the impact of iv infection on the prognosis of ards patients, compared to the other causes of ards, has been few assessed. patients and methods: systematic detection of iv in times of epidemic using rt-pcr in respiratory specimen is routine practice in our icu along with prospective data collection of patients admitted to our icu for ards with pao /fio ratio ≤ mmhg. all patients received lung-protective ventilation, the sequential organ failure assessment (sofa) score was calculated on the first days of mechanical ventilation. the primary endpoint compared the -day survival from the diagnosis of ards between patients with and without iv infection. results: from october, to may, , patients (pts) [median saps ii score = ( - ); age years ( - ); pao / fio ≤ mmhg, n = ( %)] were admitted to our icu for ards with pao /fio ratio ≤ mm/hg, including pts ( %) with iv infection (h n pdm iv a, n = ; h n a virus, n = ; b virus, n = ; associated bacteria, n = ). other main causes of ards were bacterial pneumonia without iv ( %), aspiration ( %), non-pulmonary sepsis ( %). ( %) received prone positioning, and ( %) extra-corporeal membrane oxygenation. the overall mortality rate at day- for the entire population was % ( pts ( %) with iv infection versus pts ( %) without iv infection, p = . ). kaplan-meier survival curves showed that survival was significantly higher in patients with iv infection than in those without iv infection. iv infection remained independently associated with a better prognosis at day- when entered as dichotomous variable (iv infection, yes/no) (adjusted hazard ratio (hr) = . , % ci . - . , p = . ) and when iv infection only was distinguished from other causes of ards including mixed infection iv plus bacteria (adjusted hr = . , % ci . - . , p = . ). of note, within the first days of mechanical ventilation, non-pulmonary sofa scores were significantly lower in iv patients although similar pulmonary sofa scores. conclusion: our results suggest that patients with iv related ards have less severe non-pulmonary organ dysfunctions than those with ards from other and a lower mortality at day- despite similar ards severity. compliance with ethics regulations: yes. rationale: acute respiratory distress syndrome (ards) remains frequent in intensive care unit (icu) with % to % mortality. according to joint theater trauma system, ards occurs among % of war casualties: direct lung trauma, blast lesions, burn, massive transfusion and systemic inflammatory response syndrome lead to ards development. however, there is no data reporting ards among french evacuated casualties from forward environment. our study's aim is to describe ards incidence and its severity concerning medical evacuations from war theater. patients and methods: this is an observational retrospective multicentric study analyzing all evacuated patient from war theater and admitted in icu. all patients developing ards according to berlin definition have been included. study has been approved by local ethic committee. primary study endpoint was ards developing. second study endpoints were ards severity, duration of invasive ventilation, ards treatments, icu length of stay and mortality. results: patients have been admitted in icu between and . have been excluded. a total of patients have been analyzed. % (n = ) were military aged ( - ) years. % (n = ) developed ards. we found % (n = ) war casualties, % (n = ) trauma not related to war and % (n = ) medical patients. among severe trauma, median iss was ( - ), ais thorax ( ) ( ) ( ) , and % benefited from surgery on forward environment and % (n = ) received massive transfusion. % (n = ) suffered from mild ards, % (n = ) moderate ards and % (n = ) severe ards. evacuation time was ( - ) h. at admission in icu, pao /fio ratio was ( - ) (fig. ). all patients were intubated. ards treatments used were curarization ( %, n = ), prone position ( %, n = ), inhaled nitric oxide (noi) ( %, n = ), almitrine ( %, n = ) and extracorporeal life support (ecls) ( %, n = ). invasive ventilation duration was ( - ) days, length of stay ( - ) days, and -month mortality % (n = ). conclusion: according to our study, ards among french evacuated patients from war theaters remains frequent: it occurs on % among icu admitted patients. % suffer from severe ards with % global mortality. those datas are consistent with us studies. also, we wonder if we must adapt our treatment capacities on forward environment for the most severe patients. in us army, a specialized team (acute lung rescue team) is trained to care the most hypoxemic war casualties with more treatment options as noi, ecls. compliance with ethics regulations: yes. rationale : we recently reported that septic shock patients with pneumonia exhibit a high risk of icu-acquired pneumonia, suggesting that a primary pulmonary insult may drive profound alterations in lung defence towards secondary infections ( ) . given their importance in lung immune surveillance, alveolar macrophages (am) are likely to play a pivotal role in this setting. the objective of this experimental study is to address the impact of primary pulmonary or non-pulmonary infectious insults on lung immunity. patients and methods: we established relevant double-hit experimental models that mimic common clinical situations. c bl/ j mice were first subjected either to polymicrobial peritonitis induced by caecal ligation and puncture (clp), or to bacterial pneumonia induced by intra-tracheal instillation of staphylococcus aureus or escherichia coli. respective control mice were subjected to sham laparotomy or intratracheal instillation of phosphate-buffered saline. seven days later, mice that survived the primary insult were subjected to intra-tracheal instillation of pseudomonas aeruginosa (pao strain). we assessed survival and pulmonary bacterial clearance of post-septic animals subjected to p. aeruginosa pneumonia, as well as the distribution and functional changes in alveolar macrophages. results: when compared to sham-operated mice, post-clp animals exhibited increased susceptibility to secondary p. aeruginosa pneumonia as demonstrated by defective lung bacterial clearance and increased mortality rate ( % vs. %, p < . ). in contrast, all postpneumonia mice survived and even exhibited improved bacterial clearance as compared to their control counterparts. when addressing whole-lung immune cell distribution at the time of second hit (day ), amounts of am were decreased in post-clp mice while preserved or even increased in post-pneumonia mice. antigen-presenting functions of am appeared similar in all conditions. percentages of apoptotic (annexinv + ) and necrotic ( -aad + ) am were comparable at day and day after the first hit. interestingly, both ly c high and ly c low monocytes were sustainably increased in the lungs of post-clp mice, while only transiently expanded following pneumonia, suggesting that differences in am counts could be related to modulated turnover from precursor monocytes. conclusion: using clinically relevant double-hit experimental models, a primary pulmonary infection conferred resistance to secondary bacterial pneumonia. ongoing investigations are aimed at addressing the antibacterial am functions, as well as the turnover-driving mechanisms.compliance with ethics regulations: yes. rationale: little is known on the role of exit-site signs in predicting intravascular catheter infections. the current study aimed to describe the association between local signs at the exit-site and catheter-related bloodstream infection (crbsi), which factors substantially influenced local signs and which clinical conditions may predict crb-sis if inflammation at insertion site is present. patients and methods: we used individual data from multicenter randomized-controlled trials in intensive care units (icus) that evaluated various prevention strategies regarding colonization and crbsi in central venous and arterial catheters. we used univariate and multivariate logistic regression stratifying by center in order to identify variables associated with redness, pain, non-purulent discharge, purulent discharge and ≥ local sign and subsequently evaluate the association between crbsi and local signs. moreover, weevaluated the role of thedifferent local signs for developing crbsi in subgroups of clinically relevant conditions. results: a total of patients, , catheters ( , catheterdays) and crbsi ( . %) from icus withdescribed local signs were included. redness, pain, non-purulent discharge, purulent discharge and ≥ local signs at removal were observed in ( . %), ( . %), ( . %), ( . %) and ( . %) episodes, respectively. the sensitivity of ≥ local sign for crbsi was by . %, whereas the highest specificities were observed for pain ( . %) and purulent discharge ( . %). positive predictive value (ppv) was low for redness ( %), pain ( %), non-purulent discharge ( %) and ≥ local sign ( %), but increased for purulent discharge ( . %). negative predictive values were high for all local signs. after adjusting on confounders, crbsi was associated with redness, non-purulent discharge, purulent discharge and ≥ local sign (fig. ). conditions independently associated with ≥ local sign were age ≤ years old (or . , % ci . - . , p < . ), sofa score (sofa < or . , % ci . - . , p < . ), non-immunosuppression (or . , % ci . - . , p < . ), catheter maintenance > days (or . , % ci . - . , p < . ) and insertion site (or for subclavian site . , % ci . - . , p < . ). however, the presence of ≥ local sign was more predictive for crbsi in the first days of catheter maintenance (or . , % ci . - . vs. > catheter-days or . , % ci . - . , p heterogeneity = . ). conclusion: this post hoc analysis showed that local signs were related to crbsis in the icu. local signs were independently associated with specific patient's and catheter's conditions. in the first days of catheter maintenance, local signs were predictive for crbsi. compliance with ethics regulations: yes. rationale: pneumococcal meningitis (pm) is the leading cause of bacterial meningitis in adult patients requiring icu admission and is associated with a high case fatality rate (cfr), ranging from to more than % ( ) ( ) ( ) . patients with pm may develop sepsis or septic shock that may impact management and outcomes. we aim to describe the epidemiology and outcomes of pm associated with sepsis in adult patients in france. we analysed the occurrence of pm with sepsis from to in adult patients, using the national french hospital database pmsi (programme de médicalisation des systèmes d'information). for all analyses, only the first hospital admission was considered. cases were identified using a combination of a diagnosis code for pm plus a diagnosis code for sepsis (either a code for organ failure or a procedure code for organ support). data recorded included comorbidities ( ), characteristics of the hospital stay, severity of the patients including major intracranial complications and characteristics of the infection. costs and endpoints were determined at the end of all the hospital stays related to the first admission for pm with sepsis. standardized incidence, hospital mortality, and cfr were estimated. temporal trends were assessed using cochran armitage tests of trends and linear trend analyses. results: a total of pm with sepsis aged ≥ years were hospitalized in france during - . the incidence of pm decreased from . to . per m inhabitants (p < . ) (fig. ) . most of them came from home ( %), were admitted in an academic institution ( %) and benefited from icu ( %). their median age was [ ; ] years. twothird of them had at least one comorbidity. the initial neurological presentations included coma ( %), focal signs ( %), seizures ( %) and brain stem involvements ( %). the saps ii score was [ ; ] points. the main neurological complications were cerebrovascular complications ( %), cerebral abscess ( %) and hydrocephaly ( %). pm was associated with pneumococcal septicaemia or pneumococcal pneumonia in % and % of cases respectively. the length of icu and hospital stays were [ ; ] and [ ; ] days respectively and only icu length of stay decreased over time (p < . ). the prognosis was poor since only . % of the patients were discharged to home. indeed, . % of them died and % were transferred to rehabilitation units. no temporal trends could be observed for these outcomes. the average hospital costs per case were , € [ . ; . ] . conclusion: pm with sepsis in adult in france remained a real burden associated with a high mortality rate, and disability. compliance with ethics regulations: na. rationale: mucormycosis is an emerging fungal infection, especially in patients with hematological malignancies. although this infection may lead to multi organ failure, no study has been dedicated to critically ill patients with hematological malignancy. the primary objective was to assess outcome in this setting. the secondary objective was to assess prognostic factors. patients and methods: this retrospective cohort study was performed in icus. critically ill adult patients with hematological malignancies and mucormycosis were included between and . mucormycosiswas classified as "probable"or "proven" regarding eortc criteria. variables are reported as median [iqr] or number (%). adjusted analysis was performed using cox model. results: twenty-six patients were included with a median age of years [iqr, . acute leukemia was the most frequent underlying disease (n = , %). nine patients ( %) were allogeneic stem cell transplantation (sct) recipients. nineteen patients ( %) had neutropenia and patients ( %) had received steroids. the main reason for admission was acute respiratory failure (n = , %) followed by shock (n = , %). the median sofa score at admission was [iqr, - ] points. only patients ( %) had received prior anti-fungal prophylaxis effective against mucorales. mucormycosis was "proven" in patients and "probable" in patients. diagnosis was made by histopathologic examination in patients, direct microscopy or culture in , and polymerase chain reaction in . rhizopus and mucor were the most frequent documented species. seven patients ( %) had concurrent aspergillus infection. mucormycosis was diagnosed day [− to + ] after icu admission. ten patients ( %) had pulmonary involvement whereas five patients ( %) had rhino-cerebral involvement. infection was disseminated in eight patients ( %). twenty-two patients ( %) were treated with liposomal amphotericin b. twelve patients ( %) received antifungal combination including posaconazole in . eight patients ( %) underwent curative surgery. multiple organ failure was frequent, patients ( %) requiring invasive mechanical ventilation (imv), ( %) vasopressors, and ( %) renal replacement therapy. icu and hospital mortality rates were % and %, respectively. only two patients were alive at day . three variables were associated with mortality in a cox model including allogeneic sct . ]; figure), sofa score (hr . [ % ic . - . ]) and dual therapy (hr . [ % ic . - . ]) (fig. ) . conclusion: mucormycosis is associated with a high mortality rate in patients with hematological malignancies, especially in allogeneic sct recipients. futility of icu management in these patients is to be considered and strategies aiming to improve these patients' outcome are urgently needed. compliance with ethics regulations: yes. rationale: sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. several mediators, alone or in combination, were proposed to characterize individual response, but none was proven to have good external validity. the aim of this work was to establish whether some combinations are linked to clinical phenotypes in patients with presumed sepsis, using the data collected in the captain multicenter cohort which methods and first results were previously published (parlato, icm ). patients and methods: patients were prospectively included at the time of sepsis criteria, ( %) of whom with a secondary confirmed infection. community acquired pneumonia was causal in % of infections. saps score = points [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , age = years , male sex = %. patients were followed for more than days, in whom usual icu clinical and biological parameters were collected, as well as plasma biomarkers and leucocyte associated rnas. patients were clinically classified according to their acute severity (sofa score, serum lactate), confirmed initial infection, outcome (secondary infection occurrence, icu survival). non-supervised principal component analysis of the maximal values of biomarkers assessed on first days of sepsis, and varimax rotation technique of the selected components using sas software. results: patients, med sofa day = pts, med serum lactates day = . meq/l, bacterial infection = ( %), enterobacteriaceae infection = ( %), vap and/or bacteremia after day = ( %), alive at icu d/c = ( %). five components explain % of the variance of the biomarkers. the first component ( % of the variance) was not linked to the clinical predetermined phenotypes. the second component ( % of the variance) was principally made of hla-dr rna, cd rna and cx cr rna, and linked to a lower initial severity (r = − . , p = . ), a less frequent confirmation of initial infection (p = . ), a lower occurrence of pneumonia or bacteremia (p = . ) or death (p = . ). conclusion: in our cohort, using non supervised analysis, we could separate a biomarker association linked to lower initial severity, lower rate of a bacterial cause to sepsis, and better outcome. the markers found are among those which are regularly considered as describers of the peripheral alteration of the immune system observed during sepsis (pachot, ccm ; friggeri, cc ; peronnet icm ) . compliance with ethics regulations: yes. ( ) compared a standard of care to a procalcitonin (pct) oriented use of antimicrobials for sepsis in icus. serial blood samples were biobanked in / icus ( / patients enrolled for pro-adrenomedullin (proadm) and pct concentrations). patients and methods: the aim of the study was to evaluate the respective impact of serial pct and proadm measurements in predicting relapse or superinfection and death on day *. relapse was defined as the growth of one or more of the initial causative bacterial strains (i.e., same genus, species) from a second sample taken from the same infection site at h or more after stopping of antibiotics, combined with clinical signs or symptoms of infection. superinfection was defined as the isolation from the same or another site of one or more pathogens different from that identified during the first infectious episode, together with clinical signs or symptoms of infection [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] points at amission, medical admission: ( %), immunocompromised: ( %), on mechanical ventilation ( %), pct and proadm at inclusion were [ . - . ] ng/ml and . [ . - . ] nm/l respectively. ( %) patients developed a first episode of recurrence or supereinfection after a median delay of days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and ( %) died before d . the hr maximization process proposed an optimal cut point of ng/ml for pct and nm/l for pro adm to predict d death. in the multivariate cox model, both pct and proadm were associated with death but not with relapse or superinfection (table ) . conclusion: conclusion: both serial measurements of pct and proadm are independent predictors of death in patients treated for sepsis in icu. our study confirmed the use of nm/l as a good prognosis cut point for proadm. . compliance with ethics regulations: yes. rationale: the performance of serum ( - )-β-d-glucan (bdg) and its evolution to predict the occurrence of invasive fungal infection (ifi) in a high risk non immunocompromized population remains to be determined ( ). in a post hoc analysis of the empiricus randomized clinical trial ( ), we aimed to assess the prognostic value of repeated measures of bdg on the occurrence of invasive fungal infections. patients and methods: non-neutropenic, non-transplanted, critically ill patients with icu-acquired sepsis, multiple candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between july and february in french icus were included. bdg were collected in icu at day , , , and after inclusion. a value time of more than pg/ ml, pg/ml and an increase by more than % from the previous measurement (threshold of measurement error) were assessed at baseline and overtime. for that purpose, we conducted cause specific hazard models with death as a competing risk. we also planned subgroup analyses on the placebo and the micafungin groups. cumulative risk (cumrisk) of ifi at day were derived from models. [ . ; . ] ). neither a bdg > pg/ml, nor an increase by % of bdg over time were associated with the occurrence of ifi. similar results were found in the placebo subgroup. conclusion: among high risk patients, a first measurement of bdg over pg/ml was highly associated with the occurrence of ifi. neither a cut-off of pg/ml, nor repeated measurements of bdg over time seemed to be useful to predict the occurrence of ifi. the cumulative risk of ifi in the placebo group if bdg > pg/ml is . % questioning about the potential interest of empirical therapy in this subgroup. compliance with ethics regulations: yes. rationale: since the sepsis- conference, the distinction between sepsis and septic shock is based on blood lactate value. septic shock may be encountered in the pre-hospital setting. in order to reduce the mortality, the precocity of treatments implementation has been emphasized, particularly early antibiotic administration. prior antibiotic administration, and blood culture drawing must be performed. the aim of this survey was to clarify the capabilities of french prehospital emergency service (pems) to measure blood lactate and to draw blood culture prior to hospital admission for septic shock. patients and methods: we performed an electronic survey of auto-questions addressed to the deputy chair of the french pems in . results: sixty pems ( %) participated in the survey. twenty-five percent are able to measure blood lactate and % are able to draw blood culture in the prehospital setting. ninety-five percent declared lactate measurement is helpful in assessing severity. ninety percent claimed that the lactate value influences the hospital facility, emergency department vs. intensive care unit. twenty-eight percent believe that the impossibility to draw blood culture precludes prehospital antibiotic administration. sixty-three percent estimate that a protocol for septic shock management would be beneficial. conclusion: few french pems are able to measure lactate and draw blood culture in the prehospital setting. the impact of blood lactate measurement and blood culture drawing by pems on septic shock outcome requires further studies. compliance with ethics regulations: yes. rationale: head injury is a common cause of morbidity and mortality in the first four decades of life, accounting for approximately , annual hospital admissions in the united kingdom. the majority of patients recover without intervention, however some may develop a long-term disability or even die. the early detection of pathology is therefore absolutely critical in determining patients' prognosis, helping to provide appropriate timely management. the national institute for health and care excellence (nice) adult head injury guidelines, recommend that head injuries with specific risk factors should have a ct scan within h of risk factors being identified. furthermore the provisional report should be made available within h of the scan. this audit assessed the compliance of staff to the nice adult head injury guidelines. patients and methods: the previous adult ct head scans, requested due to head injury, from the emergency department (ed) at london north west healthcare nhs trust were analysed for compliance to the nice guidelines. the standards measured were: ( ) time from request of scan to completion of scan should be within h; ( ) time from completion of scan to publication of provisional report should be within h. the locally agreed target for both standards was %. results: on review of the ct scans, ( %) were completed within h of request. from the scans ( %) not completed within the hour, were due to porter unavailability, due to an uncooperative patient and the remaining reasons were not clear from documentation. following completion of the scan, scans ( %) were provisionally reported within h. conclusion: this study highlighted a good compliance by hospital staff in ensuring patients with head injuries are managed appropriately, following detection of risk factors indicating a ct head scan. having said that, the locally agreed targets were just short of being met. one factor resulting in delayed scans was porter availability. an intervention recently introduced is the use of the "e-portering" application, which will endeavour to save time for referrers requesting porters and allow patient tracking. it is also worth educating porters, via email bulletins, on the importance of priority scans, such as ct head following injury. furthermore, the findings of the audit were relayed to the radiology department to help improve reporting times and to the ed to re-emphasize prompt requesting of ct head scans when clinically indicated. compliance with ethics regulations: yes. rationale: continuous insufflation of oxygen (cio) performed with specific endotracheal tube during cardiopulmonary resuscitation (cpr) is as effective as intermittent ventilation on endotracheal tube. experimental data suggest that cio improves the efficacy of external cardiac massage and reduces gastric dilatation. as endotracheal intubation is a cause of cpr interruption and requires skilled staff, a specific device has been developed to perform cio without intubation. this device has been implemented progressively in our fire department since . we evaluated this practice. patients and methods: longitudinal study comparing the patients with out-of-hospital cardiac arrest managed by our fire department with cio or bag-valve ventilation between january and april . patients who received mechanical chest compression were excluded. the main outcome was hospital survival. secondary outcomes were the return of spontaneous circulation (rosc) and cpr quality. univariate and multivariate analysis was performed in the whole cohort and in the sub-groups of patient with shockable and non-shockable rhythms to take into account factors associated with survival (shockable rhythm, witness, age). results: among the patients included, have been ventilated with cio and with valve-bag. the mortality was similar in the two groups (cio: . % valve-bag: . % p . ). mortality and rosc were not associated with cio in the multivariate analysis (odds ratio or . %-confidence interval ci [ . - . ] and . [ . - . ], respectively). cpr quality was better with cio than with valve-bag regarding cpr fraction (ratio of duration of chest compressions on total duration of cpr, versus % p < . ) and adequacy to the guidelines of the rhythm and depth of chest compressions ( % vs % p < . and % vs % p < . , respectively). in both subgroups of patients, cpr quality was still better with cio than with valve-bag. in the subgroup of patients with shockable rhythm, univariate analysis showed a lower mortality among the patients with cio than among the patients with valve-bag ( . % vs . % p < . ) but this difference was not confirmed by the multivariate analysis (or . ci [ . - . ], p . ). conclusion: cio without intubation is associated with an improvement of cpr quality but neither with mortality nor return of spontaneous circulation in case of out-of-hospital cardiac arrest. compliance with ethics regulations: yes. rationale: cardiovascular accidents are a leading cause of death. a cardiopulmonary resuscitation (cpr) of quality has well shown that can reduce the mortality; despite this, survival rate has not changed significantly during last years. the aim of this study is to test a new wearable glove to provide lay people with instructions during out-ofhospital cpr. patients and methods: we performed a blinded, controlled trial on an electronic mannequin ambuman to test the performance of adult volunteers, non-healthcare professionals performing a simulated cpr both, without and with glove, following the glove instructions. the group without glove, also called "no-glove" is intended as control group. each compression performed on the electronic mannequin ambuman was recorded by a connected laptop computer, drawing a depth frequency curve over the time. primary outcome was to compare the accuracy of the two simulated cpr sessions in terms of depth and frequency of chest compressions performed by the same lay volunteers. secondary outcome was to compare the decay of performance and percentage of time in which the candidate performed accurate cpr. finally, the participants were asked if the glove was useful for cpr maneuvers. the difference between the two groups in regard to change in chest compression depth over time due to fatigue, defined as decay were also analyzed. results: chest compressions were included: in control group, in glove group (table ) . mean depth of compression in the control group was . mm versus . mm in the glove-group (p = . ). compressions with an appropriate depth were not statistically different ( . % vs . %, p = . ). mean frequency of compressions in the group with glove was . rpm vs . rpm in the control group (p < . ). the percentage of compression cycles with an appropriate rate (> rpm) was . % in the group with the glove versus % in the control group, with an observed difference of . % between the two groups, which was statistically significant (p < . ,ci = %). a mean reduction over time of compressions depth of . mm (sd . ) was observed in the control group versus a mean reduction of . mm in the group wearing the glove (sd . ), but this mean difference in the decay of compressions delivery was not statistically significant (f-ratio = . , ss = . , df = , ms = . , p = . ). conclusion: the visual and acoustic feedbacks provided by the device were useful in dictating the correct rhythm for non-healthcare professionals, translating in a significantly more accurate cpr. compliance with ethics regulations: yes. rationale: neuroprognostication after cardiac arrest (ca) is a crucial issue and current guidelines recommend delayed multimodal approach. we aimed to describe reasons for death in a prospective cohort of ca patients and evaluate the diagnostic accuracy of early combined neurological prognostication tools such as automated pupillometry (ap), continuous amplitude electroencephalography (aeeg) and cardiac arrest hospital prognosis (cahp) score performed h after return of spontaneous circulation (rosc). we set up a monocentric prospective cohort of adult ca patients admitted in icu after sustained rosc and collected data according to utstein style recommendations. reasons for death were described under recently proposed classification: withdrawal of life-sustaining therapies (wlst) for neurological reasons, wlst due to comorbidities, refractory shock or recurrence of sudden ca or respiratory failure. for patients who kept abnormal neurologic state after rosc with glasgow coma scale < , we analysed accuracy of early neuroprognostication tools (ap, aeeg and cahp score) to predict poor neurological outcome, i.e. cerebral performance category (cpc) > at hospital discharge. results: patients were admitted after sustained rosc from ca during the period ( . . to . . ). in-hospital mortality was %. neurological wlst was the first reason for death ( %). exhaustive early neuroprognostication with ap, aeeg and cahp score was available for patients. among them, poor neurological outcome at hospital discharge (cpc > ) was observed for patients ( % (fig. ) . this strategy would falsely misclassificate % of patients in a good neurologic outcome category. other survivors ( %) should then be investigated with further classical delayed neuroprognostication tools. compliance with ethics regulations: yes. rationale: management delay is one of the determining factors in the assessment of emergency department quality of care. asking for a specialized advice seems to increase the time of delay. our study aimed at measuring the delays in obtaining specialized advice and identify their major causes. patients and methods: we conducted a prospective study over the period of month. we included all adult patients presenting to the emergency department who required specialized advice. data of all patients was collected. waiting times and influencing factors were studied. results: a total of patients were included. the main reason for calling for a specialized advice was to ask for a department transfer in % of cases. the time of the day when specialized advice was solicited (n (%)): in the morning ( ); in the afternoon ( ); in the evening ( ). the main solicited specialties were (n (%)): visceral surgery ( ), trauma medicine ( ), cardiology ( ), urology ( ), and pulmonology ( ). the average waiting time between calling for and getting the specialized advice was ± min. seventy-five percent of the specialized advice was obtained within h. the causes of the delay were (n (%)): physician busy in the operating room ( ), unreachable physician ( ), physician in the outpatient clinics ( ). the impact of the waiting time was (n (%)): conflict ( ), worsening patient state ( ). the average time between calling for the specialized advice and reaching a management decision was ± min. conclusion: the increasing length of stay of patients in the ed is strongly correlated to the delay in obtaining specialized advice. the implementation of a strategy to reduce the waiting time is necessary to avoid overcrowding the emergency departments and provide optimal care. compliance with ethics regulations: yes. rationale: hypnoanalgesia has been used since few years to reduce icu-patients physical and psychological discomfort during invasive procedures. however, feasibility of overall well-being management of intubated patients with hypnosis has not been described. patients and methods: we report here the hypnotic accompaniment of a -year old patient without significant medical history hospitalized in our icu for a severe gbs during months. the gbs was diagnosed by electrophysiological study and immunologic markers. patient had nearly complete paralysis of all extremities, but no facial or bulbar muscles. he received mechanical ventilation during days, including weaning time. tracheotomy was performed at day . sedative drugs were stopped days after intubation. hypnosis sessions were startedvery early after intubation by one of our trained intensivist. eight hypnotic sessions of hypnoanalgesia or hypnotherapy were performed after approval of the patient and his parents. time distribution is reported in fig. . first and second sessions were performed in order to induce relaxation and reduce anxiety. following sessions were dedicated to: ) decrease pain intensity (initially neuropathic, then induced by physiotherapy), ) attenuate the negative perception of paralysis, ) reduce the discomfort of tracheotomy ) promote the belief in healing ) facilitate swallowing exercises. furthermore the patient was quickly trained to use self-hypnosis in order to dissociate him from pain, anxiety and icu pollutions. results: feasibility of hypnosis was judged satisfactory by the operating physician, despite mechanical ventilation. after extubation, final debriefing with the patient indicates that the most efficient sessions were those focused on anxiety disorders (using the suggestion of a safe place) and suggestions of mobility (using a mangas metaphor). the patient reported very positive perception of hypnosis use. he explained that self-hypnosis was effective to reduce many discomfort. he used it frequently (generally twice a day) for a puff of anxiety or before enoxaparin injection. our observation suggests that hypnosis seems feasible in icu-awake patients and may be an interesting way to improve their icu lived experience in combination with validated measures. further investigations are needed to evaluate its effects on post-traumaticstress disorder. compliance with ethics regulations: yes. rationale: there is little medical reference for hypnosis in the intensive care field. closed specialties such as anesthesia, emergency medicine can help and refer to hypnosis for certain technical procedures. objective: to propose landmarks for a successful implementation of hypnosis by intensivists within the intensive care unit. patients and methods: this monocentric prospective observational study was performed from february to june in the -bed medical icu of brest university hospital. collected data were: characteristics of patients and hypnosis sessions performed, demographic data, physiological parameters (heart and respiratory rates) and objective and subjective evaluation of hypnosis sessions quality. results: patients were included (mean age . ± years, saps ii . ± points). hypnosis sessions were performed, of which / under mechanical ventilation. patterns of hypnosis sessions were: anxiety/comfort ( %), during a technical procedure ( %): toe, cvc placement, thoracic drainage, upper digestive or bronchial endoscopy), initiation of noninvasive ventilation or before intubation. most of time, the hypnotic trance was permitted by formal hypnosis techniques with travel and nature themes suggestion. efficacy was qualitatively assessed and rated as "total effectiveness" for % of sessions. qualitative evaluation by hypnotherapist, technical operator and observers was respectively . ± . , . ± . and ± / . heart rate decreased from ± to ± bpm and respiratory rate/min decreased from ± to . ± rpm during sessions. discussion: after a meeting, the healthcare team carried out a brainstorming to propose hypnosis in our unit. several difficulties were observed to explain implementation failures such as: finding competent patient, respiratory assistance, difficult communication, noisy environment, many nursing care, unexpected emergencies, etc.…). this experience allowed writing a vademecum to perform hypnosis in intensive care. our aims are to get more trained caregivers and to integrate hypnosis during our postresuscitation consultation, especially for post-traumatic stress. conclusion: hypnotic tools can facilitate technical procedures and improve patients' and caregivers' quality of life within the icu. compliance with ethics regulations: yes. effect of a musical intervention during central venous catheterization in an intensive care unit: the music cat prospective randomized pilot study sophie jacquier, brice sauvage, gregoire muller, thierry boulain, mai-anh nay chr, orléans, france correspondence: sophie jacquier (sophie.jacquier@chr-orleans.fr) ann. intensive care , (suppl ):f- rationale: evaluate the effect of a musical intervention on patient anxiety during a central venous access or a dialysis catheter implantation in an intensive care unit. patients and methods: the music cat study was a prospective, single-centre, controlled, open-label, two-arm randomized trial, conducted from february to february . central venous catheterization with musical intervention was compared to standard care, i.e., the usual procedure of central venous catheterization without listening to music. eligible patients had to be able to hear, understand explanations and consent. randomisation was stratified according to ventilation type (mechanical ventilation or not) and catheter site (superior vena cava or femoral vein). the music care ® (paris, france) application was used to make the patients listen to music through headphones. each patient chose his/her musical topic on a digital tablet, just before the catheterization. the primary outcome was the change in anxiety visual analogic scale (vas) between the beginning and the end of the catheterization procedure (t -tf anxiety vas). secondary outcomes included the patient's pain vas at the end of the procedure (tf pain vas). results: patients were included in the standard care group versus in the musical intervention group. main reasons for admission were the need of central catheter for chemotherapy ( , %), and sepsis and/or shock in both groups ( , %). catheters were inserted in the internal jugular vein in most cases ( , %) and about one-third were tunnelled in both groups. there was no between-group difference regarding median t -tf anxiety vas: [iqr:− to ] in the standard care group versus − [− to ] in the music intervention group (p = . ) (fig. ) , with no significant interaction between the variables of stratification or the operator experience and the intervention. the median tf pain vas was not statistically different between groups: [ to . ] in standard care group and [ to ] in music intervention group (p = . ), with no significant interaction between the variables of stratification or the operator experience and the intervention. conclusion: in this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared to usual care. as the study may have been underpowered, larger size trials are needed. compliance with ethics regulations: yes. rationale: sleep is markedly altered in icu-patients under mechanical ventilation and may be due to noise, light, patient-care activities, patient-ventilator asynchronies, or the result of acute brain dysfunction induced by sedative drugs. to our knowledge, sleep has never been studied at icu admission before any sedation. our study aimed at assessing sleep quality of non-intubated sedation-free patients admitted to icu for acute respiratory failure. patients and methods: observational study performed in a single centre of a teaching hospital. patients admitted to icu for acute respiratory failure (respiratory rate ≥ breaths/min and pao / fio < mm hg under high-flow nasal oxygen) could be enrolled. patients with hypercapnia, central nervous disease, intubated early after admission and those with a do-not-intubate order were excluded. sleep was evaluated by complete polysomnography (psg) that started in the afternoon following admission and was continuously performed until the next morning. results: over a -year period patients were screened and patients were included. among them, patients were excluded for the following reasons: patient was intubated shortly after psg initiation, psg was lost, and eeg recordings ( %) were stopped before midnight (electrodes turned off or loss of signal). therefore, patients in whom psg was complete during the nocturnal period were retained in the analysis ( rationale: convulsive status epilepticus (cse) is a common neurological emergency associated with high mortality and morbidity rates. there are strong experimental data suggesting a potential impact of secondary brain insults (sbi) on outcome after cse. however, there is no clinical proof to support this hypothesis. our objective was to evaluate the association between sbi (mean arterial blood pressure, arterial partial pressure of carbon dioxide, arterial partial pressure of oxygen, temperature, natremia, and glycemia) at day and neurological outcomes days after cse. patients and methods: this was a post hoc analysis of the hyber-natus multicenter open-label clinical trial randomized critically ill patients with cse requiring mechanical ventilation to either therapeutic hypothermia ( - °c for h) plus standard care or standard care alone. patients still alive at day after inclusion were enrolled from march to january in french medico-surgical icus. the primary outcome was favourable outcome days after cse defined as a glasgow outcome scale score of . results: median age was of years . a previous history of epilepsy was noted in ( %) patients. most episodes ( / , %) occurred out-of-hospital, and ( %) were witnessed from their onset. cse was refractory in ( %) patients and total seizure duration was min ( - ). a favorable -day outcome occurred in ( %) patients. maximal glycemia value and hyperglycemia > . mmol/l at day were the only sbi variables associated with outcome in univariate analysis. by multivariate analysis, age > years (or, . ; % ic, . - . ; p = . ), refractory cse (or, . ; % ic, . - . ; p = . ), and primary brain insult (or, . ; % ic, . - . ; p = . ) were associated with an increased risk of poor outcome, and a bystander-witnessed onset of cse (or, . ; % ic, . - . ; p = . ) was associated with a decreased risk of poor outcome. conclusion: in our population, secondary brain insults were not associated with outcome in critically ill patients with convulsive status epilepticus; whereas age, bystander-witnessed onset of status epilepticus, refractory status epilepticus and primary brain insult were identified as strong predictors of -day functional impairment. further studies are warranted to confirm our findings. compliance with ethics regulations: yes. rationale: acute stroke (as) is a leading cause of morbidity and mortality worldwide. however, data on the prognosis andfunctional outcome of patients with as requiring icu management is limited. our purpose was to identify factors associated with good outcome (defined by a modified rankin score (mrs) of - ) months after icu admission. patients and methods: retrospective cohort of patients admitted to the medical icu of a university-affiliated hospital between january and december and coded for acute stroke using the icd- criteria. patients with traumatic stroke and isolated subarachnoid hemorrhage were excluded. results: we identified patients. median age was [ . - ] years and ( . %) were males. main reasons for icu admission were coma ( %), hemodynamic instability ( . %), acute respiratory failure ( %), and cardiac arrest ( . %). glasgow coma score at icu admission was [ ] [ ] [ ] [ ] [ ] [ ] [ ] and points. types of stroke were hemorrhagic in ( . %) patients and ischemic in ( . %). mechanical ventilation was required in patients ( . %). seizures occurred in . % of the patients and convulsive status epilepticus in . %. pneumonia was diagnosed in ( . %) patients (aspiration pneumonia n = , ventilator associated pneumonia n = ). thrombolysis or thromboaspiration were performed in ( %) patients with ischemic stroke. surgical evacuation of expanding hematoma was performed in ( . %) patients, ( . %) had craniectomy, and ( . %) had external shunt for hydrocephalus. icu and hospital mortality were . % and %, respectively. six months after icu admission, ( . %) patients had a good outcome (mrs - ), ( . %) had significant disability (mrs - ), and ( . %) were deceased (lost follow-up n = , . %). on multivariable analysis, age (or . per year ( . - . ), p = . ), saps (or . per point ( . - . ), p = . ), and hemorrhagic stroke (or . ( . - . ), p = . ) reduced the likelihood of good outcome (mrs - ) months after icu admission. conclusion: in our study, prognosis of acute stroke requiring icu admission was poor and a good functional outcome occurred in less than % of the patients at months. age, severity at icu admission, and type of stroke predicted outcome. compliance with ethics regulations: yes. rationale: in intensive care units, severe spontaneous hemorrhagic brain injuries have a poor prognosis for mortality and functional outcomes. affected patients face particular ethical issues regarding the difficulty of anticipating their eventual recovery. in this context, prognostic scores can help clinicians in patients/relatives counseling and therapeutic decisions. the previous reviews pointed out many prognostic tools for intracranial hemorrhage and subarachnoid hemorrhage but did not focus on injuries explicitly severe nor assessed the methodological limitations of the models. our systematic review aimed to assess methodologically prognostic tools for functional outcomes in severe spontaneous haemorrhagic brain, with particular attention to their clinical utilities. patients and methods: following prisma recommendations, we queried medline, embase, web of science, and the cochrane by february , . we included multivariate prognostic models explicitly developed or validated on adults with severe intracranial or subarachnoid haemorrhage. we evaluated the articles following the charms recommendations (checklist for critical appraisal and data extraction for systematic reviews of prediction modelling studies) and the tri-pod statements (transparent reporting of a multivariable prediction model for individual prognosis. results: our review confirmed the multiple publications of prognostic scores, as we found articles aiming to develop or validate prognostic tools. relying on guidelines, we discarded articles due to the lack of prognostic capacities, validation, or predictor selection. articles developed and validated a prognostic tool and externally validated existing models (fig. ) . no score was of good methodological quality in intracranial hemorrhage. we highlighted two prognostic scores in subarachnoid hemorrhages: the sahit predicting unfavorable outcome or mortality at months and the fresh predicting unfavorable outcome at months. conclusion: although prognostic studies on haemorrhagic brain injuries abound in the literature, they generally lack of methodological robustness or show incomplete reporting. with the numerous published scores, we believe that it is time to stop developing new scores. ongoing validation, recalibration, and impact studies would keep improving existing good tools. the use of "patient-centered" approaches could also enhance them, and be more appropriate to inform patients and families about their long-term potential recovery. these considerations should drive future research in the modern era of neurocritical care prognosis. compliance with ethics regulations: na. rationale: respiratory pattern analysis by a visual examination is an important part of clinical assessment but is dependent on caregiver expertise and is subjective. furthermore, there is no easy medical device used in picu to measure tidal volume (vt) and minute ventilation (mv) in spontaneous breathing patients. the clinical research unit in critical care of chusj and ets have developed a non-invasive computerized d video analyzing system (retract system) to detect and perform a video analysis of respiratory status in children. the aim of this study is to test the reliability of the retract system to monitor respiratory distress in critically ill children. the retract system is detailed in reference . in summary, cameras reproduce in d the thorax and abdomen of a subject. the respiratory status (respiratory rate (rr), tidal volume (vt), minute ventilation (mv)) assessed by the retract system was compared on a bench test (high-fidelity mannequin) and in critically ill children, to the ventilator measurements and clinician expert evaluation (gold standard). bland-altman plots were used for comparison. results: we observed a significant agreement, on mannequin, between retract system and gold standard method in estimating vt, rr and mv, i.e. % of the paired differences were within the limits of agreement in bland-altman plots, as illustrated in fig. . in critically ill children (n = ), the correlation between the pairs of measures was also high (r > . , p < . ) and thecoefficient of determination with a high fit ( . < r < . , p < . ). for good correlation, the retract system needed to have a visual access to thorax and abdomen in a quiet subject. the retract system measurements of vt, rr and mv for respiratory distress monitoring in patients seems reliable. more testing are required to validate this method in usual practice and to develop the retractions signs video analysis. compliance with ethics regulations: yes. rationale: severe bronchiolitis requires hospitalization in paediatric intensive care unit (picu). non-invasive ventilation (niv) has been demonstrated to treat them since twenty years, its use is well defined but there is no consensus for the weaning. this study evaluated the application of a nurse-driven niv weaning protocol in hospitalized infants with severe bronchiolitis and verified its safety. this was a retrospective monocentric study in a picu of robert debré hospital-paris, france. in the epidemic period of bronchiolitis between and , all patients under one year old with severe bronchiolitis and requiring niv were included. two groups were compared: one group using the nurse-driven niv weaning protocol and one group without using this protocol. occurrences of complications, duration of ventilatory support and length of stay (los) in picu and total los were compared. results: patients were included in the study, in the no-protocol group, and in the protocol group. the nurse-driven protocol was using at the rate of % (n = / in the protocol group (p = . ). picu los were . days [ ] [ ] [ ] in the no-protocol group versus days [ - . ] in the protocol group (p = . ), hospital los was days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the no-protocol group versus days [ ] [ ] [ ] [ ] [ ] [ ] in the protocol group (p = . ) (fig. ) . the use of this first nurse-driven niv weaning protocol was feasible and simple with a very good application rate. its utilization was safe. the occurrence of complications did not increase by the use of this protocol. it would allow an optimal niv weaning without prolonging the ventilatory support duration nor picu los or hospital los. the professional practices appeared to be coordinated and the nurses appeared to be more autonomous. compliance with ethics regulations: yes. no-protocol and protocol groups comparison: cpap duration ( ), ventilatory support duration ( ), picu los ( ), hospital los ( ) rationale: first-line management of severe acute bronchiolitis in infants is mainly based on non-invasive ventilation (niv) and high-flow nasal cannula (hfnc) therapy. however, pediatric data regarding weaning from niv/hfnc are lacking. this study aims to identify the weaning practices from niv/hfnc in children with severe bronchiolitis. the weaniv-survey is a cross-sectional survey. a questionnaire was sent to french-speaking physicians with key roles in pediatric intensive care units. results: a total of % ( / ) of french university hospital were represented in the study. only % of pediatric centers used a protocol for weaning from niv/hfnc and nurses were considered as key-actors of the weaning process for half of participants. continuous positive airway pressure (cpap) was the mode of ventilation mainly used as the first-line therapy in clinical practice. the main criteriaconsidered toinitiate weaning process were: noor slight respiratory distress, a fio < %, a respiratory rate < /min and no significant apnea. three strategies to discontinue niv/hfnc were identified: /gradual decrease of ventilatory parameters (pressure or flow), /abrupt discontinuation and /gradual increase in off-ventilation time. abrupt weaning strategy was the most commonly used, no matter the mode of ventilation. a significant level of respiratory distress, the presence of apneas, an increase in oxygen requirement, and a respiratory rate > / min were identified as weaning failure criteria by most pediatric intensive care physicians. conclusion: in most centers, the weaning process does not follow any protocol. abrupt weaning seems to be commonly used as weaning strategy in children with severe bronchiolitis supported by niv/hfnc. based on the study findings, we suggest that criteria for weaning initiation and for weaning failure must be defined and weaning protocols generated. compliance with ethics regulations: yes. complications secondary to prone positioning occured for patients ( . %). conclusion: this first study, which evaluate prone positioning efficacy in severe p-ards shows evidence that prone positioning improves oxygenation parameters and survival rate. these results highlight the necessity to develop a multicentric prospective randomized study to confirm these conclusions. compliance with ethics regulations: yes. ( vs ) and vasoactive-inotropic score (vis) ( vs ) were significantly higher in the non-survivor group. cannulation was veno-venous ( %) or veno-arterial ( %) and patients ( %) were finally not initiated on ecmo. we observed an increase of patients cannulated in our picu over time (fig. ). there was no significant difference in mortality between patients transported on ecmo after cannulation in our picu and those who were transported to be cannulated in a referral ecmo center. the median time between the decision and the cannulation was . h and the median time taken in charge by picu transport team was approximately h. these periods were not significantly different between cannulation on site or in an ecmo center and between survivors and not-survivors. conclusion: in our study, multiple organ dysfunction, particularly hematologic and acuterenal failures, seems to be a risk factor of mortality. the delay between decision and management is similar whatever the cannulation site. specific ecmo mobile team and picu transport team seem to be essential, fast and trained to transfer these patients. it would be interesting to compare our cohort with children requiring ecmo already hospitalized in a referral ecmo center. compliance with ethics regulations: yes. rationale: life expectancy in patients with metastatic breast cancer (mbc) has substantially improved over the last decade. life threatening complications result from advanced diseases, infection and treatment-related toxicity. only few studies have assessed outcomes in this setting. we performed a hospital-wide study to investigate how icu resources are needed in patients with mbc. patients and methods: all patients with mbc managed at our hospital between and were retrospectively included. the primary outcome was overall survival (os). factors associated with icu mortality were identified using a multivariable cox proportional hazard model with sensitivity analysis. results are expressed as median [interquartile ranges] unless stated otherwise. results: among the patients managed at our hospital, ( %, including male) were admitted to the icu ( [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] patients per year). age was [ - ] years. patients were receiving their nd [ st- rd] line of treatment and had [ ] [ ] metastatic sites. sofa score at admission was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . main reason for icu admission was sepsis (n = , %), acute respiratory failure (n = , %), coma (n = , %) and metabolic disorder (n = , %). invasive mechanical ventilation was required for patients ( %) and renal replacement therapy for ( %). sixteen ( %) patients died in icu. following icu discharge, median os was . months ( % ci [ . - . ]) and / ( . %) patients died within months. an antineoplastic treatment was resumed for / ( %) patients alive after icu discharge. factors independently associated with mortality were performance status ≥ (hr . , % ic [ . - . ] ) and sofa score at day (hr . per point, % ic [ . - . ] ). after sensitivity analysis, the number of treatment lines at icu admission was not associated with mortality. conclusion: icu admission is required in the course of the mbc disease for % of the patients. determinants of short term outcomes rely on performance status and disease severity but not on the characteristics of the underlying disease. ongoing analyses will assess whether icu survivors reach life expectancy of patients never admitted to the icu. compliance with ethics regulations: yes. hubert gheerbrant , jean-françois timsit , nicolas terzi , stephane ruckly , mathieu laramas , matteo giaj levra , emmanuelle jacquet , loic falque , denis moro-sibilot , anne-claire toffart chu grenoble alpes, grenoble, france; aphp, paris, france; outcom-erea, bobigny, france correspondence: hubert gheerbrant (hgheerbrant@chu-grenoble.fr) ann. intensive care , (suppl ):p- rationale: the prognosis of critically ill cancer patients admitted in intensive care unit (icu), remains an issue. our objective was to assess the factors associated with -and -month survival of icu cancer survivors. patients and methods: based on the french outcomerea ™ database, we included solid cancer patients discharged alive, between december and november , from the medical icu of the university hospital in grenoble, france. patient characteristics and outcome at and months following icu discharge were extracted from available database. results: of the cancer patients with unscheduled admissions, ( %) were discharged alive from icu. the main primary cancer sites were digestive ( %) and thoracic ( %). the -and -month mortality rates were % and %, respectively. factors independently associated with -month mortality included ecog performance status (ecog-ps) of [ ] [ ] . . - . ). interestingly, cancer chemotherapy prior to icu admission was independently associated with lower -month mortality (or, . ; % ic: . - . ). among patients with an ecog-ps - at admission, % (n = ) and % (n = ) displayed an ecog-ps - at and months, respectively. at months, ( %) patients received anticancer treatment, ( %) were given exclusive palliative care. discussion: factors associated with -month mortality are almost the same as those known to be associated with icu mortality. we highlighted that most patients recovered an ecog-ps of - at and months, in particular those with a good ecog-ps at icu admission, and could benefit from an anticancer treatment following icu discharge. conclusion: these results should be taken into account when deciding upon icu admission. it is of paramount importance to have an evaluation of both patient's general condition and anticancer treatment opportunities following icu discharge. compliance with ethics regulations: yes. rationale: the decision to urgently initiate medical anti-cancer treatment in cancer patients admitted to intensive care unit for cancerrelated organ failure is an issue. we currently lack criteria to select patients who may benefit from the treatment initiation. the purpose of our exploratory study was therefore to evaluate the characteristics of patients whose medical anti-cancer treatment is initiated in icu and to identify prognostic factors for in-hospital mortality. in these patients. patients and methods: we analyzed retrospectively, over a period of years ( / / to / / ), cancer patients over -year old admitted to our icu bordet and in whose anti-cancer medicaltreatment was initiated during in-icu stay. to identify prognostic factors for in-hospital mortality, we carried out a multivariate analysis of the factors influencing this mortality, considered as a binary. we also analyzed the long term survival of patients alive after their hospital stay (from the day of going out of hospital). results: overall, patients were included, men ( %) and women ( %), with a median age of years ( - ). of these, patients ( %) had a solid tumor and ( %) had a hematological tumor. in-icu mortality is % ( % ci - %) and in-hospital mortality % ( % ci - %). the prognostic factors for in-hospital mortality were age (mean vs in those who survived), the sofa score (median vs ), the saps ii score (mean vs ), the charlson score (mean vs. . ), the number of organ failure (mean . vs . ) and the presence of a therapeutic limitation (ntbr stated within h: % vs %). survival at year of patients who survived the hospital stay was % and median survival time was estimated to be . year ( % ci . - . ). in patients with a solid tumor, -year survival was % and % in those with a hematological tumor (p < . ). conclusion: we observed, in selected cancer patients admitted to the icu for a cancer-related complication, that the initiation of an anti-cancer medical treatment is feasible and can lead to interesting results, particularly in patients with a hematological tumor. compliance with ethics regulations: yes. rationale: considerable progress in the management of onco-hematology (oh) malignancies led to an increase in the number of patients proposed for intensive care unit (icu) admission. several guidelines offer decision models for icu transfer of these patients. we aimed to describe prognosis, adequacy of icu admission and denial in oncohematology patients. we included all oh patients proposed for icu admission in a tunisian medical icu, between january and july . from an admission proposal registry, were collected patient underlying condition, functional status, malignancy and predicted prognosis, acute critical illness and its reversibility, adequacy of icu rationale: cancer patients frequently need intensive care support for a life-threatening condition due to the underlying neoplasm or an adverse therapy-related event. however, there are poor data on their characteristics and outcomes in the intensive care setting. the aim of the present study was to describe clinical characteristics and to identify factors associated with in-icu mortality in critically ill cancer patients. patients and methods: it is a retrospective study conducted in the medical icu of farhat hached teaching hospital between january and december . all cancer patients with complete records were included. baseline characteristics, clinical parameters, severity of illness, primary tumor location and outcomes were collected. univariate and multivariate regression analyses were carried out to identify factors independently associated to poor prognosis. rationale: prognostic impact of underlying malignancy seems limited in most studies assessing outcome of critically ill cancer patients [ ] . however, only limited number of characteristics, namely disease progression status and preexisting stem cell transplantation, were usually assessed [ ] . primary objective of this study was to assess influence of hematological malignancy aggressiveness on hospital outcome. secondary objective was to assess influence hematological malignancy aggressiveness on type of infection. patients and methods: post-hoc analysis of prospective multicenter cohort performed in hospitals in france and belgium and including critically ill adults with underlying hematological malignancy admitted in icu from jan to may . a cox model was used to adjust for confounding variables then a propensity score matching on characteristics associated with underlying malignancy aggressiveness was performed. results: of the included patients, ( . %) had low grade malignancy (lg), the most frequent being myeloma (n = ), chronic lymphocytic leukemia (n = ), and myelodysplasia (n = ). patients with lg malignancy were older, underwent more frequently autologous stem cell transplantation (sct) and had less frequently altered performans status. they had more severe organ failure at icu admission (sofa score [ ] [ ] [ ] [ ] [ ] [ ] vs. [ ] [ ] [ ] [ ] [ ] [ ] , p = . ). before adjustment, mortality was % (n = ) and . % (n = ) respectively in patients with and without lg malignancy (p = . ). after adjustment for confounder using a cox model, a higher mortality was associated with nonlow grade malignancy (or . ; % ic . - . ). a propensity score then allowed a : matching upon variable associated with malignancy aggressiveness. after matching unadjusted mortality was % (n = ) in patients with lg malignancy and . % (n = ) in patients with high grade malignancy (p = . ) (figure) . in the matched cohort and after adjustment for confounder, high grade malignancies were associated with lower mortality (or . ; % ic . - . ). risk of fungal infection was unchanged by underlying malignancy before adjustment ( % vs. . % of patients with and without lg malignancy; p = . ) or after adjustment (hr . ; % ic . - . ). conclusion: despite anti-cancer advances, aggressiveness of hematological malignancies is associated with overall icu outcome. lowgrade malignancies displaying a better prognosis than non-low grade. aggressiveness of the underlying malignancy is not associated with risk of fungal infection. compliance with ethics regulations: yes. rationale: guillain-barré syndrome is the most common cause of acute flaccid paralysis and is associated with pulmonary embolism due to the mobility limitation. the aim of this study is to describe the incidence, the severity of pulmonory embolism in patients admitted to an intensive care unit (icu) for guillain-barre syndrome (gbs). patients and methods: twenty-eight adults patients with confirmed diagnosis of gbs were admitted to the icu in our university hospital center over a -year period and they were all included. prevalence, risk factors and course of vte were analyzed in icu patients with various forms and severity of gbs. results: during the study period, adult gbs patients were included. five ( . %) developped pulmonary embolism. the mean age was . ± . years and the sex ratio was . . the comparaison betewen the groups with and without pe showed that factors associated with the development of this complication were: respiratory failure requiring mecanical ventilation (p = . ), infectious complications (p < . ), blood pressure lability (p = . ), the delay of icu admission (p = . ), the delay to treatment initiation (p = . ), the sofa score (p = . ) and the presence of quadriplegia (p = . ). conclusion: pulmonary embolism is a frequent complication in patients with gbs. factors associated with this complication were: respiratory failure requiring mecanical ventilation, infectious complications, the delay of icu admission, the delay to treatment initiation, a high sofa score and the presence of quadriplegia. preventive measures in this category of patients have to be improved. rationale: acute respiratory distress syndrome (ards) is a life-threatening pathology associated with very high morbidity and mortality ( - %) in intensive care units (icu) and with even higher mortality among the severly burned patients worldwide ( à %). the aim of our study was to describe in tunisia burn patients with ards and to identify prognosis factors. patients and methods: we conducted a descriptive retrospective study between - - to - - , in burns icu, in ben arous, in tunisia. all burns who presented an ards, according to the berlin definition, during their stay in the icu, were included. when clinical or gasometric data was uncomplete, these patients were excluded. results: during the study period, patients were admitted to our burn unit including ventilated patients. fifty patients presented an ards: fifteen patients were excluded for lack of information, and patients were retained. the sex ratio was . . patients had a mean age of ± years, an average burned area of % ± %, an average unit of burn skin score (ubs score) of ± and an average sequential organ failure assessment score (sofa score) of . none of the patients had a history of cardiovascular or pulmonary diseases. the average time of onset of ards was ± days. ards was mild in case, moderate in and severe in . the etiology of ards was pulmonary in cases ( %) and extra-pulmonary in ( %). the pulmonary ards had as cause pneumonia isolated in patients, an isolated pulmonary burn in patients and a combination of pneumonia and lung burns in patients. extra-pulmonary ards were all due to sepsis and mainly to bacteremia. septic shock was associated with ards in patients ( %). the treatment was a conventional treatment based on protective ventilation, curarization and prone positioning in addition to the etiological treatment. the average length of stay in icu was days and mortality was % in these patients. conclusion: mortality from ards in burns in tunisia, is important especially in those with pulmonary burns as well as those with sepsis. the introduction of new treatments, such as extracorporeal membrane oxygenation, remains essential to improve the prognosis of burn patients. compliance with ethics regulations: yes. rationale: aspiration pneumonia (ap) is common in intensive care unit (icu). the incidence of ap among adults hospitalized with pneumonia ranges between and . %. usually one or more risk factors are identified to be involved in ap. the aim of this study was to determine the risk factors and predictors of mortality on patients with ap. patients and methods: we retrospectively included patients aged more than years and who were hospitalized in our icu for ap. patients were excluded if they had history of tuberculosis, if they have bronchiectasis or metastatic brain tumor. results: a total of patients were included. history of diabetes, hypertension, epilepsy and ischemic stroke were found respectively in . %, . %, . %, and . % of cases. the reason of icu admission were coma ( %), acute respiratory failure ( %), poisoning ( %) and cardiac arrest ( %). the incidence of acute respiratory distress syndrome (ards) was %. the most common organism isolated was staphylococcus aureus ( cases). risk factors for ap were epilepsy ( %), swallowing disorders ( %), ischemic stroke ( %), copd ( %) and degenerative neurological disease ( %). the mortality rate was . %. the median duration of mechanical ventilation was days [iqr - ]. in multivariate logistic regression analysis; saps ii score (or = . , % ic [ . - . ], p = . ) and ards (or = . , % ic [ . - . ], p = . ) were independently associated with mortality. conclusion: risk factors for aspiration pneumonia were epilepsy, swallowing disorders and ischemic stroke. ards and saps ii score were independent predictive factors of mortality. compliance with ethics regulations: yes. undetermined. the aim of this study was to evaluate the impact of hyperoxia on morbidity and mortality. patients and methods: this was a prospective study performed in the icu of abderrahmen mami hospital during a -month period. all patients admitted in icu during the study-period were included. those who didn't need oxygen therapy or in end of life stage were excluded. arterial blood gases were analyzed daily and each day with at least one value of oxygen arterial saturation (sao ) > % was considered as a day with hyperoxia. for each patient included, the number of times and days spent in hyperoxia was recorded as well as complications during the icu stay and the outcome. results: during the study-period, patients were included but only were eligible. mean age was ± years. acute on chronic respiratory failure was the most frequent reason of admission ( %). non-invasive ventilation was required for % of patients and invasive mechanical ventilation was necessary in % of cases. overall mortality was %. hyperoxia was observed in % of cases, with an average of ± times during the icu stay and ± days. a statistically significant association was observed between a long duration of hyperoxia and the occurrence of ventilator acquired pneumonia (p < - ), ventilator acquired bronchitis (p = . ), acute respiratory distress syndrome (p < - ), atelectasis (p < - ), septic shock (p < - ), rythm disorders (p = . ), reintubation (p < - ) and tracheostomy (p = . ). on multivariate analysis, independent factors of mortality were: simplified acute physiology score ii, cardiac failure, need for invasive mechanical ventilation and septic shock. hyperoxia was not independently associated with mortality. conclusion: hyperoxia is frequent in icu. it is significantly associated with icu complications but not independently associated with mortality. compliance with ethics regulations: yes. experience of the practice of prone position in patientswith acute respiratory distress syndrome in intensive care (chu oran) nabil ghomari, soumia benbernou, djebli houria faculté de medecine d'oran, oran, algeria correspondence: nabil ghomari (nabilghomari@hotmail.fr) ann. intensive care , (suppl ):p- rationale: mechanical ventilation (mv) in the prone position (pp) and low tidal volume have become recommendations with a high level of scientific evidence in recent years. the pp has been practiced for years in the chu oran emergency resuscitation service. we wanted to report the service experience in the practice of pp in patients with ards. patients and methods: retrospective study performed in patients with severe hypoxia ards with spo < % under fio > % or pao /fio < during the period march to december . results: patients received ventilation in pp. ards was secondary to thoracic trauma in % of patients, septic shock in % and aspiration pneumonitis in %. analysis of the success factors and improvement of oxygenation found that lobar ards, the delay < h and a duration of pp ≥ h were statistically significant. conclusion: the pp must be integrated into the arsenal of care of the patients in ards especially in our country where we do not have all the therapeutic options. compliance with ethics regulations: yes. julien goutay, nicolas cousin, thibault duburcq, erika parmentier-decrucq chu de lille, pôle de réanimation, hôpital salengro, lille, france correspondence: julien goutay (julien.goutay@gmail.com) ann. intensive care , (suppl ):p- rationale: in veno-venous extracorporeal membrane oxygenation (vv-ecmo) therapy, blood flow is the main determinant of arterial oxygenation and should be - ml/kg/min in adults. this flow rate is determined by several factors including the size of the inflow cannula. the impact on clinical outcomes of arterial cannula's size in veno-arterial ecmo (va-ecmo) has already been studied, and showed no difference for survival to discharge, weaning success rate and initial flow rate between a small cannula group and a larger one. our first objective was to describe the impact of inlet cannula size on the assistance flow rate in patients treated with vv-ecmo. secondary objectives were to analyze its impact on ecmo weaning, mechanical ventilation characteristics and mortality. patients and methods: we retrospectively reviewed all cases of respiratory failure treated with vv-ecmo admitted in the medical intensive care unit (icu) of lille's teaching hospital from january st, through march st, . inlet cannula size was collected and divided into two groups: the "small cannula" group had inlet cannula less than or equal to fr, while "large cannula" were larger than fr. primary endpoint was the initial flow rate according to the inlet cannula size, and its changes during the first h of assistance. secondary endpoints were the analysis of predictive factors associated with the choice of a larger inlet cannula, and the impact of its size on clinical outcomes such as successful ecmo weaning. results: patients treated with vv-ecmo were admitted in our hospital. eleven ( %) were cannulated with a large inlet device. mean initial ecmo flow rate was statistically higher in the "large cannula" group than in the "small cannula" one: . l/min (± . ) versus . (± . ) respectively, p < . . the difference was also significant during the first h of assistance. we found no difference between the two groups on clinical outcomes such as ecmo weaning time. in univariate analysis, weight was heavier in the "large cannula" group [ (± ) kg] than "small cannula" [ (± )], p < . . conclusion: ecmo initial flow rate was higher in a "large inlet cannula" group (internal diameter more than fr) compared with a "small cannula" group. we found no correlation with cannula-related haemorrhagic or thrombotic complications. inlet cannula size did not influence ecmo weaning, and duration time, but this may be a lack of statistical power. further prospective studies should confirm this results. compliance with ethics regulations: yes. rationale: burn patients are at risk of multidrug-resistant (mdr) bacterial infections with high mortality rate. therefore, monitoring the emergence of mdr pathogens in these vulnerable patients is important. this study aimed to assess digestive colonization with carbapenemase-producing gram-negative bacilli (cp-gnb) in patients admitted to the burn intensive care unit. patients and methods: our study was prospective and conducted over a one-year period (january to december ). every admitted patient was subjected to the screening. a double swab set was used to collect rectal swab specimens. one swab was used for mdr screening by disk diffusion method on selective media; the other for multiplex real-time pcr (cepheid's genexpert ® ) allowing detection of the most common carbapenemase-encoding genes (ceg) (blaoxa- , blakpc, blandm, blavim and blaimp). results: among the studied patients, ( . %) were detected positive at admission for cp-gnb by the genexpert ® carba-r assay. eleven patients, initially not colonized, acquired positive faecal carriage subsequently during their hospital stay. forty-two colonized patients ( . %) developed cp-gnb infection during their hospitalization. the ceg blandm quantitatively dominated by far with detections; either alone ( cases) or associated with other ceg ( cases). the second most frequent gene was blaoxa- . it was detected alone eight times and in association with other ceg times. forty-three patients carried blavim gene, usually in association with other ceg ( %). however, only one patient carried blakpc gene. the parallel screening by classical microbiology methods (disk diffusion on selective media) detected the presence of cp-gnb in all molecular positive samples. conclusion: our study describes the characterization of carbapenemase in burn patients and highlights their alarming spread. this emphasizes the importance of an active surveillance program by early detection of cp-gnb carriers and an isolation policy to limit the mdr infections expansion. compliance with ethics regulations: yes. rationale: invasive fungal infections are increasingly observed in the icus especially in burn units. inthe absence of simple and accessible techniques for early microbiological diagnosis, the use of antifungal treatment is increasing. little is known about the extent of the problem of antifungal prescription in burn icus. we aimed to evaluate the antifungal prescription in major burn patients. patients and methods: during the study period ( - ), all prescriptions of antifungals were analysed. analysis concerned demographics, clinical circumstances, as well as the basis of antifungal prescribing (targeted vs. empiric). among the patients admitted in this period, patients were treated with antifungals (sex ratio: . ; mean age: ± years, with low associated comorbidity). the tbsa was . % [ . - . ], ubs was [ . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . most of the patients ( . %) were transferred from another hospital structure within ± h. antifungal treatment was started at the average of the seventh day post wound injury, more often on an empiric basis. sofa score at the beginning of the treatment was ± . . lymphopenia was present in % and thrombopenia was present in %. index of colonisation was positif only in cases. the average candida score was . ± . . microbiological results were tardily collected, within weeks, in %. fungal urine infections were found in cases. candidemia and catheter-related infections were considered only in cases. the risk factors of fungal infection as described in literature were found in most of the patients including mechanical ventilation ( . %), length period of stay ( days [ . - . ]), central venous line ( %), severe sepsis or septic shock ( %), large-spectrum antibiotherapy for more than days ( %). conclusion: the management of antifungal infections in major burn patients is still challenging. antifungal prescription is based on clinical presumption. the empirical prescription reflects the lack of efficient laboratory support and late microbiological results prompting physicians to rely on clinical informations. the management of fungal infections is based on the improvement of mycological investigations. compliance with ethics regulations: na. rationale: invasive candidiasis is a widespread and alarming infection in intensive care units (icu) patients. its diagnosis is often difficult because of the lack of specificity of clinical signs and the low sensitivity of blood cultures. while the candida albicans species remain the most common cause of bloodstream infections, non-albicans are emerging. these infections are serious, associated with high mortality rate and requiring early diagnosis and appropriate treatment. in tunisia, few data are available. we aimed to determine the epidemiological profile of a series of candidemia in icu, the risk factors associated with the occurrence of candidemia and to describe the modalities of the mycological diagnosis of candidemia and their etiological profile. patients and methods: a retrospective longitudinal descriptive study conducted in the parasitology-mycology laboratory with the collaboration of the medical icu of la rabta hospital-tunis over a -year period from january , to december , . all hospitalized icu patients with at least one candida-positive blood culture were included. results: forty-three patients among hospitalized patients during the study period had at least one candidemia infection. the main risk factors for development of candidemia infection include invasive procedures, a prior use of antibiotics and parenteral nutrition. c. albicans was the most common species, detected in . % of patients. nonalbicans candida species were prominent ( . %), represented by c parapsilosis, followed by c. tropicalis and c. krusei then c. glabrata and finally c. lusitaniae. all the isolates tested were sensitive to the common antifungal agents. the mortality rate of our patients was high ( . %), and the detection of the albicans species in blood cultures was the only prognostic factor identified (or = . [ . - . ], p = . ). conclusion: candidemia in the medical icu patients is common and is associated with high mortality rate. despite the progress of biological tools, the diagnosis is difficult and needs to take into account the risk factors of the patients as well as scores based on clinical and microbiological parameters. a better identification of risk patients may help to early initiate empirical antifungal treatment. compliance with ethics regulations: yes. necrotizing soft-tissue infections in the intensive care unit: a retrospective hospital-based study kais regaieg, sabrine nakaa, arnaud mailloux, madjid boukari, johana cohen, dany goldgran-toledano groupe hospitalier intercommunal le raincy-montfermeil, montfermeil, france correspondence: kais regaieg (kais.regaieg@gmail.com) ann. intensive care , (suppl ):p- rationale: the objective of our study is to describe the epidemiological and clinical characteristics of necrotizing soft-tissue infections (nsti) and to improve therapeutic management. we conducted a retrospective observational study that included patients admitted in the intensive care unit (icu) of general hospital between september and aout with a primary or secondary diagnosis of nsti. we collected demographic and clinical data, cultured pathogens, lengths of stay, and in-icu mortality. results: during the study period, a total of patients admitted to the icu were diagnosed with nsti ( . % of the total number of patients). the mean of age was years. the sex ratio (m/w) was . . ten patients ( %) were directly admitted to the icu, others were transferred from medical or surgical wards. the mean of saps ii was . ( . ). the main indication to admission in icu was shock ( %). the most common comorbidity was diabetes ( %). the other co-morbidities associated with nsti were cardiovascular diseases ( %), obesity ( %) and carelessness ( %). the sites most commonly affected were extremities in patients ( %) and abdomen/ano-genital in patients ( %). in icu, a total of patients ( %) were mechanically ventilated [ (median duration: . days ( . )], patients ( %) were given vasopressors, and patients ( %) underwent renal-remplacement. all patients underwent one or more chirurgical intervention. patients ( %) underwent radical necrosectomy. in cases, an amputation was necessary. polymicrobian infection was seen in patients ( %). in patients ( %), we used vacuum assited closure therapy, which in patients was followed by definitive reconstruction by split skin grafts. the mortality in icu was %. the mean stay in icu was days . the mean duration of hospitalization of the patients who survived was days ( - ). on the basis of a univariate analysis, higher saps ii score and lactate levels were associated with increased mortality (p < . ). conclusion: ntsi is rare in icu but it's a life-threatening and disabling disease with a high mortality requiring a multidisciplinary management. early diagnosis and adequate treatment are necessary to improve clinical outcome and must be known by everyone. more studies are needed to estimate the interest and delay of new strategies such as negative pressure therapy. compliance with ethics regulations: yes. rationale: nosocomial infections remain a major cause of mortality and morbidity in burn patients. providing information about the main causative bacterial agents and determination of their susceptibility to antibiotics may improve empiric therapy and early detection of emerging antimicrobial resistance. the aim of our study was to investigate the species distribution and antibiotic susceptibility of isolated strains from a burn intensive care unit (icu). patients and methods: this study was performed retrospectively on all bacteriological samples taken from the burn icu at the trauma and burn center in tunisia during a seven year period (from january to december ). all isolated microorganisms were identified on the basis of standard microbiological techniques. antibiotic susceptibility testing was carried out by the agar disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. minimum inhibitory concentration of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may . results: during the study period, the most frequent identified species were pseudomonas aeruginosa ( . %), staphylococcus aureus ( %), klebsiella pneumoniae ( . %) and acinetobacter baumannii ( %). these strains have been mainly isolated from blood cultures ( %) and skin samples ( . %). pseudomonas aeruginosa resistance to ceftazidime increased from . % in to . % in and resistance to imipenem and ciprofloxacin was . % and . %, respectively. four strains were resistant to colistin. rationale: community-acquired peritonitis is a heterogeneous condition characterized by peritoneum inflammation in response to a bacteria injury. the aim of our study is to describe the epidemiological, clinical, bacteriological, etiological, therapeutic characteristics of community peritonitis, and to evaluate the prognostic factors. patients and methods: this is a retrospective descriptive and analytical study spanning three years (between january and december ) involving cases of community peritonitis, hospitalized in the surgical emergency resuscitation department p ibn rochd casablanca university hospital. our study included adult patients with community-acquired peritonitis who underwent medical and surgical management. the studied parameters are the demographic data, the clinical and paraclinical signs, the care taken and the evolution of the patients. the study showed that the mean age was . ± . years, with a sex ratio of . . patients medical history included tobacco ( . %), extra-abdominal signs [hemodynamic failure ( %), renal failure (n = , %), hematological disorders (n = , %) and respiratory disorders (n = , %)]. therapeutic management was based on perioperative resuscitation, treatment of organ failure, probabilistic antibiotic therapy and median laparotomy surgery. the main etiologies of community peritonitis were: digestive perforation ( . %), purulent effusion ( %), intestinal necrosis ( . %), cholecystitis ( . %). intraoperative bacteriological specimens yielded the following bacteriological profile: predominance of ngb ( . %) dominated by e. coli ( . %) followed by klebsiella pneumoniae and enterobacter cloacae ( . %) the mean hospital stay was . ± . days. the mortality rate was . %. conclusion: improvement in the prognosis of community-acquired peritonitis can only be achieved by constant assessment of very early diagnosis and initiation of appropriate resuscitation and antibiotic therapy associated with a complete surgery carefully codified according to guidelines. compliance with ethics regulations: yes. rationale: klebsiella pneumoniae carbapenemase (kpc)-producing bacteria are a group of emerging highly drug-resistant gram-negative bacilli causing infections associated with significant morbidity and mortality. the aim of our study is to point out the incidence of bloodstream infections (bsi) caused by kpc in icu patients, its clinical presentation and course. patients and methods: we conducted a retrospective descriptive study. all patients hospitalized in the icu of our hospital who developed bsi caused by kpc from january , to december , were included. results: during the study period, patients were included. the mean age was . ± . years ranging from to years. sex ratio (m/f) was . trauma was the major cause of hospitalization in cases ( %). the most common past medical diseases were arterial hypertension in patients ( %). length of hospital stay prior to icu admission was ± . days. at infection onset, mean saps ii was ± . , mean sofa was . ± . and mean apache ii was . ± . . during icu hospitalization, all patients required invasive mechanical ventilation during . ± . days, had a central venous catheter (cvc) and an indwelling urinary catheter in place, patients ( . %) had tracheotomy, ( %) underwent surgery, ( %) presented acute kidney failure and ( %) needed hemodialysis. before the isolation of kpc, all patients presented infections. antibiotics prescript were: colistin in patients ( %), carbapenems in patients ( %), amoxicillin/clavulanic acid in patients ( %), cephalosporins in patients ( %), fluoroquinolones in patients ( %), tigecycline in patients ( %), aminosids in patients ( %), rifampicin in patients ( %), fosfomycin in patients ( %), glycopeptides in patients ( %). the delay for kpc-bsi onset was . ± . days. the most common infection sources responsible of kpc-bsi were: cvc in patients ( %) and pneumonia in patients ( %). kpc infection was responsible of septic shock in patients ( %). resistance rates were: gentamycin ( %), amikacin ( %), colistin ( %), fosfomycin ( %) and tigecycline ( %). antibiotics used to treat kpc bloodstream infection were resumed in table . the mean length of icu stay was . ± . days. out of the included patients, patients died (the mortality rate was %). death was related to kpc infection in patients. conclusion: the high prevalence of kpc-bsi in icu patients dictates the importance of implementation of infection control measures and strict antibiotic policies. compliance with ethics regulations: not applicable. we identified episodes of nosocomial infections in patients, representing a cumulative incidence rate of . per exposed patients. the incidence density was . infections per days of hospitalization. the prevalence of pneumonia was . %, followed by urinary tract infections . %, central venous catheterization infections . %, bacteriemia . %, meningitis . % and surgical site infections . %. the incidence rate of intubation-related pneumonia was . / day of exposure. the incidence rate of bladder-related urinary tract infection was . / day of exposure. the incidence rate of positive culture of the central venous catheter was . / day of exposure. the incidence rate of bacteremia related to stay was . / day of exposure. the mortality rate was . % with a significant difference between infected and uninfected patients (p = . ). microorganisms were gram negative bacteria in % of cases. conclusion: epidemiological surveillance of healthcare-associated infections is needed to establish prevention plans. compliance with ethics regulations: not applicable. in the prehospital setting, early identification of septic shock (ss) with high risk of mortality is essential to guide hospital orientation (emergency department (ed) or intensive care unit (icu)) prior to early treatment initiation. in this context, the severity assessment is most of the time restricted to clinical tools. in this study, we describe the association between prehospital shock index (si) and mortality at day of patients with ss initially cared for in the prehospital setting by a mobile intensive care unit (micu in this study, we reported an association between prehospital si and mortality of patients with prehospital ss. a si > . is a simple tool to assess severity and to optimize prehospital triage between ed and icu of patients with ss initially cared for in the prehospital setting by a micu. the association of si with biomarkers may be helpful to improve the screening for ss and decision making of ss in the prehospital setting. compliance with ethics regulations: yes. the failure rate and complications were comparable between the groups, but the ultrasound-guided internal jugular catheter appears to be faster to insert and requires fewer punctures, so it could be an alternative to the femoral one in emergency situations. rationale: neuromyelitis optica (nmo) is a rare but severe disease. the prognosis of treated nmo attacks remains unclear. we evaluated our practice, the early evolution and the prognosis of nmo patients. patients and methods: an observational study was performed on patients with nmo attacks presenting with visual or medullar symptoms admitted for plasma exchange (pe) therapy from january to august . treatment efficiency was defined as a negative shift of the visual or motor disability score (edss). nonparametric mann-whitney and fisher exact tests were used for statistical analysis as required. results: twenty-four patients had pe sessions. characteristics of the cohort are described in table . ( . %) died from complications of nmo attacks. treatment had an effect in ( . %) patients. the shift in the ambulatory and visual edss was respectively − . + . and − . + . . the non-survivor patients had all aqp antibodies (p < . ). residual edss was higher in the non-survivor group ( . + . vs . + . , p < . ). pulse steroids were administered in ( %) patient in the non-survivor group vs ( %) patients in the survivor group (p < . ). twelve ( %) patients previously given pulse steroid therapy responded to pe. discussion: we assessed the handling of nmo attacks and identified our flaws. we concluded that pulse steroid therapy should not be withheld or replaced by lower dosage. we also need to find a way to make attacks identified by physicians earlier to shorten the delay between its onset and patient's admission in a specialized care unit. we observed that the mean improvement is modest during the early phase of our treatment. but a modest improvement in the edss can have a great impact in the patient's quality of life and even survival. conclusion: nmo attacks remain a threatening disease despite aggressive treatment. shortening the delay of treatment and ensure adequate pulse steroid therapy coupled to pe could be a way to improve the prognosis. compliance with ethics regulations: yes. rationale: acute kidney injury in trauma patients is a problem that has been little studied in the intensive care unit (icu). its occurrence has been shown to be associated with high morbidity and mortality. we aim to determine the outcome of icu trauma patients with acute kidney injury (aki), including the incidence of death in the icu, of nonreversible renal impairment and icu complications. patients and methods: this is a prospective study, conducted in the department of emergencies and icu, including trauma patients with a minimum icu stay of days. renal failure was defined based on the new kdigo classification. predictors of mortality and poor outcome were identified using univariate and then multivariate analysis. results: one hundred and fifty patients were admitted during the study period for the management of post-traumatic injuries, among which patients were included. the incidence of aki in the studied population was % ( cases) with ( %) diagnosed with stage one, ten ( %) with stage two and ten ( %) with stage three. the overall mortality of patients with post-traumatic aki was . % ( patients) with a mean icu lengh of stay (los) at ± days and of days on ventilator at ± . eight patients ( . %) needed renal replacement therapy and thirty-four had non-reversible renal impairement ( %). during icu stay, eight patients ( %) were diagnosed with pulmonary embolism. on univariate analysis, the following variables were associated to mortality in patients with post-tramatic aki including; age, hemodynamic instability on the day of diagnosis and bilirubin levels on the day of aki diagnosis. besides, according to our analysis, the use of renal replacement therapy and the non-reversibility of renal impairment during icu stay were also associated to icu mortality. among these factors, the non-reversibility of renal impairment in the icu was a predictor of mortality on multivariate analysis (p = . , or = , . in this cohort, the following variables were predictive of non-reversible renal impairment during icu stay; including age (with a best cut-off of years old), medical history of hypertension, higher iss and diuretics' administration. on multivariate analysis, the age (p = . , or = . , ci . - . ) and use of diuretics (p = . , or = , ci . - ) were associated to non-reversible aki in the icu. conclusion: our study confirms that post-traumatic aki in the icu is associated to high morbidity and mortality. the identification of outcome predictors could be valuable to guide the management of aki. compliance with ethics regulations: yes. rationale: the occurrence of acute kidney injury (aki) in trauma patients is a problem that has been little studied to date. its presence has been shown to be associated with an increased risk of morbidity and mortality in affected individuals. to determine the incidence of post-traumatic aki and identify its predictive risk factors that could be eventually prevented. patients and methods: this is a -month long prospective cohortstudy, conducted in the department of emergencies and intensive care unit (icu) of a university hospital, including trauma patients with a minimum icu stay of days. renal failure was defined based on the new kdigo classification. predictors of aki were identified using univariate and then multivariate analysis. results: one hundred thirty patients were admitted during the study period for the management of post-traumatic injuries, among which patients were included. the incidence of aki in the studied population was % ( cases) with ( %) diagnosed with stage one, ten ( %) with stage two and ten ( %) with stage three. on univariate analysis, older age and medical history of diabetes or hypertension were predictors of aki. injury assessment found traumatic brain injury (ais > ), glasgow (gcs) on admission, and the diagnosis of fat embolism to be associated to post-traumatic aki. moreover, hemodynamic instability on admission and during icu stay, shock-index on admission, the amount of fluid administered the use of vasoactive drugs, sepsis, hyperbilirubinemia, p/f ratio and acute respiratory distress syndrome (ards) were also associated to post-traumatic aki. among these factors, ards (p = . , or = , ci - ), fat embolism (p = . , or = , ci . ) without preload-dependence, and were unclassified. multivariate analysis (using variables collected prior to hypotension) identified the following variables as risk factors for the occurrence of hypotension associated with preload-dependence: preload-dependence before hypotension (odds ratio = . , p < . ), fluid removal rate by crrt (or = . per increase in sd, p < . ), and lactate levels (or = . per increase in sd, p < . ). in this single center study, preload dependence-associated hypotension was slightly more frequent than hypotension without preload dependence in icu patients undergoing crrt. testing for preload dependence to adjust fluid removal could help prevent hypotension incidence during crrt. rationale: few studies report the relation between functionnal brain alterations during and after icu stay and abnormalities of cbf displayed on tcd. using vti as hemodynamic parameter is unusual for evaluation of cbf. the purpose of this preliminary study was to compare the values of vti of healthy controls (c) versus icu (p) with usual parameters (i.e. diastolic (vd) and mean velocities (vm), resistance (ir) and pulsatility index (ip)). rationale: accurate diagnosis of the level of consciousness is a challenge and different states such as coma, vegetative state (vs) or minimally conscious state (mcs) are often confused while they convey meaningful prognostic information. this distinction rely on the coma recovery scale-revised (crs-r) gold-standard. however, this clinical scale is imperfect since unresponsive patients can exhibit genuine signs of consciousness using advance neuroimaging techniques. expanding the range of behaviors indexing consciousness at bedside is thus of decisive importance. patients and methods: we designed and proposed a new clinical sign of mcs, the habituation to auditory startle reflex (asr), based on the blink response to repeated sounds: either inhibition of the automatic asr response (extinguishable) or nohabituation (inextinguishable response). we prospectively tested this new sing in patients suffering from disorders of consciousness after severe brain injury and first compared its diagnostic performances with the current gold-standard (crs-r) using standard discrimination metrics (auc, sensitivity, specificity, likelihood ratios) and their % confidence interval. we then investigated the correlates of this new sign on two validated neuroimaging diagnostic procedures (multivariate eeg-based classification of the state of consciousness and fdg-pet metabolic index of the best preserved hemisphere) using an anova with the state of consciousness and the asr response as independent variable. rationale: although continuous electroencephalography (ceeg) is commonly recommended in neurocritical care patients, implementation of this monitoring in routine is facing the need for a specific training of professionals. we evaluated the effectiveness of a training program for the basic interpretation of ceeg to critical care staffs in a prospective multicentre study. patients and methods: after completion of a pre-test, participants (physicians and nurses) recruited in french intensive care units (icu) received a face-to-face eeg learning course, followed by additional e-learning sessions at day- (post-course), day- , day- and day- , based on training tests followed by illustrated and commented answers. each test was designed in order to evaluate knowledge and skills through correct recognition of predefined eeg sequences covering the most common normal and abnormal patterns. the primary objective was to achieve a success rate of more than % of correct answers at day- in at least % of participants. results: among participants, ( . %) completed the full training program and of these ( . %) full-training participants achieved at least % of correct answers at day- . paired comparisons between scores obtained at each evaluation demonstrated a statistically significant increase over time. at day , rates of correct answers were greater than % for all predefined usual eeg sequences, excepted for the recognition of periodic and burst-suppression patterns and reactivity, which were identified in only . % ( % ci . - . ) and . % ( . - . ) and . ( . - . ) tests, respectively. discussion: this multicentric prospective study, which evaluated a training program for the basics of electroencephalography offered to critical care teams, provides interesting information about the training process and its impact on learners according to their different characteristics. we believe that participants reflect the heterogeneity of the various use of ceeg in the critical care setting. participants came from university and non-university icus, and whereas some of them used to monitor patients with ceeg, others were in an implementation process when the last monitored neurocritical care patients with intermittent eeg. in accordance with previous studies, we focused to the entire medical and nursing icu staffs. conclusion: a -months training program aiming to teach the basic interpretation of continuous eeg in the intensive care units was associated with a significant attrition in participation over time. however, participants who received the full training program were capable to accurately recognize the vast majority of eeg patterns that are encountered in critically ill patients. compliance with ethics regulations: yes. mourad goulmane oran hospital and university center, oran, algeria correspondence: mourad goulmane (goulmane.mourad@univ-oran . dz) ann. intensive care , (suppl ):p- rationale: cerebral venous thrombosis (cvt) is a rare but very serious disease with various clinical and etiological aspects. unlike ischemic arterial accidents, epidemiological studies are limited. the aim of our work was to study the clinical, etiological and evolutionary features of cvt in the algerian population from a sample of patients. patients and methods: this is a retrospective observational study conducted in the neurology department of the chu d'oran between january and december . in a clinical context suggestive of cvt, the diagnosis of certainty was provided by brain mri coupled with mra. all subjects benefited from a complete etiological assessment. the anticoagulant treatment was based on the low molecular weight heparin relayed by the anti-vitamin k. the duration of the follow-up was months. results: the mean age was . ± . years, the sex ratio was ( f/ h), the onset was subacute in % of cases. the main early signs were headache ( . %), visual disturbances ( %), epileptic seizures ( . %) and motor deficit ( . %). thrombosis predominated in the upper sagittal sinus and lateral sinuses; parenchymal lesions were associated in / of the cases. gynecologic obstetric causes were by far the most frequent. the evolution was favorable in . % of the cases. discussion: cvt is characterized by its clinical polymorphism, its predominance in young women, and its most often favorable evolution. the causes are multiple and often intricate requiring the realization of a systematic etiological assessment even if the cause seems obvious. the treatment of choice remains early anticoagulation, based on heparinotherapy even in case of hemorrhagic softening. the characteristics of cvt in the algerian population are distinguished by a high frequency of gynecological obstetric causes. awareness campaigns for women of childbearing age are useful. compliance with ethics regulations: not applicable. rationale: the ct-dragon score was developed to predict longterm functional outcome after acute stroke in the anterior circulation treated by thrombolysis. its implementation in clinical practice is hampered by the plethora of variables included. in addition, the score has not been validated in important subgroups such as stroke patients undergoing thrombectomy. given these limitations, the current study was designed to evaluate the use of a simplified score based on machine learning, as a possible alternative. this single-centre retrospective study included patients treated for stroke, in the anterior and posterior cerebral circulation, between - and - . at days, favourable (modified rankin scale (mrs): - ) and miserable outcome (mrs: - ) were predicted by ct-dragon. machine learning selected the aim was to describe the adherence rates to gold guidelines in critically ill copd patients and to identify predictors of low adherence. patients and methods: a prospective cohort study conducted from december to april in a -bed medical intensive care unit of farhat hached hospital. all adult patients admitted for aecopd during the period of the study were included. demographic and clinical data were recorded. adherence to gold was evaluated. univariate and multivariate regression analyses were carried out to identify factors independently associated to non-adherence to gold guidelines. results: seventy-seven patients were recruited. patients' characteristics were : mean age, . ± years; male ( . %); median duration of the disease, [ - ] years; mmrc scale ≥ , ( . %); health insurance coverage rate, ( %); pulmonologist follow up, ( , %); frequent exacerbator (≥ exacerbations in the last year), ( . %); median exacerbations episodes, [ ] [ ] [ ] . long-term oxygen use and home mechanical ventilation were respectively used in ( . %) and ( . %). eight ( . %), ( . %) and ( . %) belonged to copd groups b, c and d, respectively. pharmacological treatment included: saba-ics combination, ( . %), laba-ics, ( . %), laba-lama, ( . %) and lama-laba-ics, ( . %). overall adherence to gold guidelines treatment recommendations for the different stages of copd was ( . %). two patients ( . %) were over treated and ( . %) were undertreated. inappropriate treatment rate was ( %) in gold b, ( . %) in gold c and ( . %) in gold d. univariate analysis identified two factors associated with non-adherence to gold : the absence of pulmonologist follow-up ( % vs. . %; p = . ) and the low income ( . % vs. . %; p = . ). in multivariate analysis only the lack of pulmonologist follow-up was identified as an independent risk factor associated with gold guidelines discrepancies (or, ; % ci [ . - . ]; p = . ). there is a lack of adherence to gold guideline treatment recommendations in tunisian copd patients. this may lead to severe exacerbations. discrepancies were due to the poor access of severe copd patients to an appropriate pulmonologist follow-up. compliance with ethics regulations: yes. the operating theaters concerned were: the otolaryngology block, ophthalmology, vascular and thoracic surgery, and gynecological surgery. all patients over years of age were enrolled using the clinical parameters of difficult intubation (arne score > ), which will benefit from orotracheal intubation. the main judgment criteria were: first-pass success rate, intubation time, which is defined as the time between inserting the slide into the patient's mouth and obtaining the capnography curve, the cormack-lehane score and the pogo score (percentage of opening of the glottis). statistical analysis used spss software. results: a total of patients were included. no cases of failure with this device were observed, the duration of intubation was on average . s (only cases required more than min). the cormack-lehane score and involved patients ( . %), and the pogo score greater than % involved patients ( . %). one case required the features of the simplified score. discrimination, calibration and misclassification of both models were tested. results: % had proximal anterior stroke, % proximal posterior stroke and % lacunar infarcts in either circulation. in % no thrombus was objectivated. % of patients were treated with thrombectomy, % received thrombolysis and % underwent both thrombolysis and thrombectomy. % only received anti-platelet therapy. the area under the receiver-operating-characteristic curve (auc-roc) for ct-dragon was . ( % ci . - . ) for favourable and . ( % ci . - . ) for miserable outcome. r ofct-dragon was . and . for favourable (lack of fit, p = . ) and miserable (lack of fit, p = . ) outcome respectively. misclassification rate was % for favourable and % for miserable outcome with ct-dragon. selection of predictors from the ct-dragon was done by logistic regression, bootstrap forest and decision tree analysis. nih stroke scale, pre-stroke mrs and age were identified as the strongest contributors to favourable and miserable outcome, and included in the simplified score. auc-roc was . ( ci% . - . ) and . ( ci% . - . ) for the prediction of favourable and miserable outcome respectively. r was . and . for the prediction of favourable (lack of fit p = . ) and miserable (lack of fit p = . ) outcome respectively. misclassification rate was % for favourable and % for miserable outcome with the simplified score. the simplified score had better discriminative power than ct-dragon for both outcomes (both p < . ). the ct-dragon score revealed acceptable discrimination in our cohort of both anterior and posterior circulation strokes, receiving a variety of treatment modalities. the simplified score had a better discrimination, while maintaining comparable and good specificity and misclassification rate for miserable outcome. the simplified score needs further validation in a prospective, multi-centre study. compliance with ethics regulations: yes. rationale: the gold report represents a major revision to gold strategy guidelines. it brings new recommendations regarding diagnosis, severity assessment, and both pharmacologic and non-pharmacologic treatment of copd. however, adherence to evidence-based therapeutic guidelines is often poor in low-income developing countries and represents a significant barrier to optimal management. the setting up of an lma-fastrach (desaturation). a case of glottic edema has been noted. discussion: this study shows a very high success rate with this technique ( . % in the first trial and . % in the second trial), in the context of a predictable difficult intubation. the video-airtraq allows a very good visualization of laryngeal structures, a shortening of the duration of intubation, and is rarely responsible for immediate or secondary complications. all the data in the literature go in the same direction. conclusion: at the end of this work, our perspectives are to update the difficult intubation procedure, integrating the video-airtraq into our algorithm, as well as into our difficult intubation trolley. to take into consideration the cost of this device to eventually generalize it to all our structures. compliance with ethics regulations: yes. ) and beds of continuous monitoring. the activity of the cp is organized in a medical visit in the morning and in conducting projects in the afternoon. the activity is presented using a -years balance sheet results: the activity of pharmaceutical interventions (pi) or answers to requests from teams is shown in table . the solicitations doubled the second year. the cp is involved in the conduct of internal or polar projects (set up of cooperative sedation, nutrition…), the good use of health products (relay iv/po, infusion, crushed tablets and compatibility with gastric probe, drug incompatibilities, proton pump inhibitors…), the efficiency of the drug circuit (link with the pharmacy, reflection on the improvement of the circuit, regular meetings with nurses), medico-economic analysis of health products spending and the formalization of actions by protocolisation. he is also very involved in clinical research: patient screening, clinical study setup: blipic study (beta-lactam's dosing in pneumonia in icu in patients treated by continuous renal replacement therapy; clinicaltrials nct ) or in candiarea project (invasive infections to candida and preemptive treatment guided by biomarkers; in progress). a satisfaction survey submitted at months to nurses ( answers/ ) or to doctors/ residents ( / ) reported cp competence in the accompaniment of teams (> %) [in medico-economical, contribution of knowledge, vigilance reflex…], relevance of information transmitted (> %) [administration of drugs, dosage adjustments, …] and his relationship adapted to the units (> %) [communication, availability] . the development of clinical pharmacy in icu involves mastery of the specificities of icu by the cp, requiring a learning period and relationships adapted to clinical situations and teams. many health products projects specific to critical care are coordinated by the cp and made possible by medical and paramedical involvement. the cp appears as a vector of good use both in medical (reasoned prescription) and paramedical (good practices) with increasing solicitation of teams since his arrival. this reception has been facilitated by an innovative approach of clinical pharmacy deployment in our icu on an impulse of the clinical pole compliance with ethics regulations: yes. predicting models such as the news has been developed in the emergency department, but it has only been fewly evaluated in the icu. heart rate variability (hrv) reflects the autonomic nervous system response in various pathological situations and may vary according to patients' physiological status. the rox index, which reflects the acute respiratory failure severity, seems to be a good predictor of high-flow nasal canula failure. the aim of this study was to evaluate the potential value of news, hrv and irox (inversed rox) as poor outcome predictors, using artificial intelligence and machine learning. a retrospective analysis of a prospective datawarehousing project (reastoc clinicaltrials identifier nct ) on icu patients who did not require invasive ventilation. physiological parameters were collected on admission, within a -h delay. news, hrv (in time, frequency, and non-linear domains), and irox were computed and integrated into the prediction model. analysis was performed using medcalc and matlab machine-learning work-package. results: one hundred and twelve patients were included. patients who died in the icu (n = ) had highest news as compared with icu survivors ( . [ . - . ] vs. . [ . - . ] respectively; p = . ). the irox was higher ( . [ . - . ] vs. . [ . - . ], p = . ) and most hrv parameters also depicted higher values for icu survivors. considering a composite icu prognostic outcome parameter (mortality and/or need for any form of respiratory assistance and/or an icu los > median los), there was also a difference for news, hrv and irox (p < . ). the best value to predict icu mortality for news was (auc = . , p = . ), irox > . (auc = . , p = . ) and hrv (shannon entropy) > . (auc = . , p = . ). the best model to predict the need fo respiratory assistance combines irox and hrv (sd /sd ; auc = . , p = . ). adding shannon entropy on this model predicts either the need for respiratory assistance and icu survival (respectively auc . , p = . and auc . , p = . ). in icu spontaneously breathing patients, news, irox and hrv are different in between survivors and patients who died. the best model to predict the need for respiratory assistance combines irox and hrv (sd /sd ). compliance with ethics regulations: yes. rationale: sepsis is known for its important mortality in critically ill patients. the last guidelines defined sepsis as life threatening organ dysfunction. it rejected the concept of systemic inflammatory response syndrome (sirs) associated to suspected or confirmed infection, and considered the concept of dysregulated response to infection. actual guidelines recommend the quick sequential organ failure assessment score (qsofa) to identify patients with sepsis especially when outside intensive care unit. thus, outcomes have mainly to judge the value of sirs in the sepsis- era. the purpose of our study was to compare whereas qsofa score or the sirs criterion are superior to predict in-hospital mortality, shock and mechanical ventilation use in sepsis. our study includes patients in whom the sepsis- definition is met. therefore, this inclusion was retrospectively performed throughout emergency department (ed) admission cases for clinically suspected infection. we collected patients admitted to ed for sepsis. mean age was years ± with bornes of and . men were % of the patients. death occurs in . % of patients, sepstic shock in % and the use of mechanical ventilation in . %. qsofa ≥ has a significant association with in-hospital mortality (p < . ) but not sirs ≥ ( . ). neither qsofa ≥ nor sirs ≥ has association with the use of mechanical ventilation (p = . vs. p = ). whereas, both have a significant association for prediction of septic shock. the absolute sensitivity and negative predictive value in our study can be explained by the small size of our sample. this needs confirmation with literature data about the fact that sirs criterion are superior in term of sensitivity and npv than qsofa to predict septic shock. despite the weak odds ratio (or) of sirs before that of qsofa and the poor specificity and positive predictive value (ppv), we can conclude that sirs according to its sensitivity and npv, seems to persist useful in the sepsis- era as a reliable prognostic tool in the ed. this may need more large studies for confirmation. conclusion: despite sirs has no significant association with mortality in sepsis, it has largely higher sensitivity and superior npv to predict septic shock than qsofa in ed. compliance with ethics regulations: yes. our study aimed to determine the predictive factors of mortality in our patients. retrospective study over years in the intensive care unit of the hospital august. all patients with septic shock were included. a p value < . was considered significant. results: patients were collected. the age ranged from to years old. the average duration of hospitalization in pre-intensive care was days. the reasons for admission: (febrile respiratory distress: % of cases, polytrauma: % and % for sepsis), the most frequent infections: pulmonary ( %) and blood ( %). % received prior antibiotic therapy and % were immunocompromised. the overall mortality was %. the analytical study of the data shows that the age, the length of stay before admission in intensive care and that in intensive care, fever, hypothermia, slimming, hypotension, collapse, failures (respiratory, hematological, renal, hepatic and neurological) and the use of catecholamines are correlated with mortality, whereas sex, chest pain, tachycardia or bradycardia and mottling are not predictive of mortality. conclusion: despite improved techniques for the diagnosis and treatment of patients with septic shock, mortality remains high, especially in the presence of certain risk factors, hence the value of prevention in immunocompromised patients and the reduction in their length of stay in a hospital setting. compliance with ethics regulations: yes. conclusion: p. mirabilis is among the leading bacteria responsible for nosocomial infections in icu. they are emerging highly drug resistant pathogens whose incidence is rapidly increasing in icu. so that, it early identification with in vitro testing is of paramount importance to the success of infectioncontrol efforts. compliance with ethics regulations: not applicable. rationale: influenza is a potential lethal disease causing dozens of thousands excess deaths per year both in europe and in the united states. besides hygiene procedures, vaccination is a cornerstone of influenza prevention and guidelines recommend for vaccination among health workers (hw), especially if they are in close contact with frail people. despite these recommendations, the vaccination coverage is low among health workers both in europe and in the us. the relevance of a mandatory vaccination for health workers is currently a hot topic but data are scarce regarding intensive care unit health workers' opinion. patients and methods: health workers from medical, surgical and polyvalent icus received a link to the electronic record of the survey. results: among the icus, icu health workers (hw) (medical: and paramedical: ) were questioned. three hundred and forty-one icu ( %) answered, ( %) medical health workers (mhw) and ( %) paramedical health workers (phw) (p < . ). among mhw / ( %) were vaccinated vs only / ( %) phw (p < . ). discrepancies exist between medical and paramedical icu health workers' opinions and beliefs about vaccination for influenza and its acceptance. medical health workers were more prone to consider influenza as a potentially lethal disease occurring not only among frail people but also in healthy people, to consider the vaccine efficient and safe. to agree with "vaccination for influenza is mostly related with gain for pharmaceutical industry" (or: [ . - ] ) and to disagree with "the risk of guillain-barré syndrome is higher after an episode of influenza than after vaccination for influenza" (or: . [ . - ] ) were independently associated to the disagreement with a mandatory vaccination for icu hw. conclusion: vaccination for influenza should be strongly recommended as a tool of individual protection for icu health workers as for general population. as confidence in vaccine efficacy and concerns about vaccine side-effects impact the vaccination rate, objective information should be provided to icu health workers about the efficacy and the side effects of vaccination for influenza. compliance with ethics regulations: yes. rationale: intra-abdominal infections are a major cause of morbidity and mortality. sfar recommendations on this topic were published in february . the purpose of this work was to evaluate whether our antibiotic therapy was adequate for these recommendations and whether they were adapted to our unit. the secondary objectives were to look for different risk factors for mortality, to evaluate the impact of inappropriate antibiotic therapy, to evaluate the relevance of carbapenem prescription. this is a single-center retrospective observational study of secondary peritonitis in the tourcoing intensive care unit. for each peritonitis, the epidemiological data and the co-morbidities of the patients were collected. bacteriology and anti-infectious therapies were described to determine the rates of adaptation of our antibiotic therapy and that recommended by sfar. the adequacy of our treatments to the recommendations was also quantifiable. the description of the stay, the occurrence of a death was specified. results: peritonitis were included. the rate of adaptation of the sfar antibiotic therapy was %. the rate of adaptation of our antibiotic therapy was % and its adequacy rate of %. the main differences in prescriptions concerned over-prescription of antifungals, molecule against gram positive bacillus and a sub-prescription of aminoglycosides and beta-lactams, in particular carbapenems. the different mortality risk factors found were sofa score > (or . % ci . - . ), the charlson score > (or . % ci . - . ), the hollow organ perforation (or . % ci . - . ). a comparison of the appropriate or not antibiotic groups did not reveal a significant difference in mortality, number of surgical revision and length of stay. in % of nosocomial peritonitis, antibiotic therapy with carbapenem was recommended. after recovery of microbiological data, it was only necessary for . % of cases. conclusion: our work showed a low rate of compliance with sfar recommendations. these recommendations are applicable to our service by providing a particular reflection for fungal infections. our study does not show a correlation between mortality and inadequate antibiotic therapy, surgery remaining the major treatment. compliance with ethics regulations:yes. rationale: acinetobacter baumannii is a gram-negative opportunistic bacteria that has gained several drug resistance mechanisms over the last decades. analysis of a. baumanii's resistance profile helps to establish a prompt control and a prevention program. the aim of this study was to evaluate the epidemiology and antimicrobial resistance of a. baumannii isolates in a trauma and burn center in tunisia. patients and methods: retrospectively, we studied all strains of acinetobacter baumannii isolated over a -year period (from january to december ). conventional methods were used for identification. antimicrobial susceptibility testing was performed with the disk diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. data were analyzed using the sir-system. minimum inhibitory concentration (mic) of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may . results: during the study period, non-repetitive strains of acinetobacter baumannii were isolated representing . % of all isolates, % of gram-negative bacilli (gnb) and . % of non-fermenting gnb. in our center, infections due to a. baumannii were endemic with epidemic peaks. a. baumannii was mainly isolated from burn intensive care unit ( %) and anesthesiology department ( . %). the most frequent sites of isolation were blood cultures ( . %), catheters ( %), respiratory specimens ( . %) and skin samples ( % sampling duration is also reduced, improving workflow. evaluators consider that bronchosampler rationalizes the cumbersome sampling process and that the closed system design reduces the risk of losing sample or sample contamination. the set-up, the suction capacity, the sampling quality and quantity have all been evaluated better or far better than that usually observed with usual sampling techniques and devices. finally, ( %) of users prefer bronchosampler to commonly used method. conclusion: this satisfaction survey shows that with its simple but revolutionary design, bronchosampler brings a real effective benefit in sampling procedure enabling the clinician to perform it alone, and ( %) of the survey evaluators consider that bronchosampler should replace their current practice. compliance with ethics regulations: yes. rationale: the possibility of having a sensitive, specific and prognostic biological marker for bacterial infections is a considerable challenge. a step was taken with the discovery of pracalcitonin. patients and methods: this is a prospective observational cohort study of patients in the medical resuscitation department of the university hospital of casablanca during the -month period, including patients in whom the pct was dosed. the data collected allowed us to form two groups according to the pct value: pct+ group with pct > ng/ml and pct− group with pct < ng/ml. the statistical analysis of these different data was carried out using epi info software version . . . results: % of our patients had a bacterial infection and % did not have one. we also distinguished community infections ( % of i+ patients) and nosocomial infections ( % of i+ patients). we found that the highest rates of pct were in nosocomial infections and the lowest pct rates were found in community-acquired infections. then, in each type of organ involvement we tried to vary the pct thresholds to . - and ng/ml in order to find the best threshold for which pct allowed to diagnose bacterial infection, justifying our choice of departure. we concluded that the best pct cut-off value in general was ng/ml, because it gave us the best sensitivity/specificity ratio ( % and % respectively) with a positive predictive value of % and a negative predictive value of %. the link between pct and bacterial infection was moderate (yule q-factor at . ). by analyzing the different therapeutic aspects, we showed that % of our patients had been treated with atb before the pct assay and that the broadest spectrum antibiotics available to our service were used in patients with pct levels the highest. finally, concerning the evolution, the higher the rate of pct, the higher the death rate, especially since % of patients with pct > ng/ml died. conclusion: procalcitonin is considered to be one of the best markers of systemic bacterial infection. indeed, its elevation is earlier than that of crp and its specificity is better compared to il- and il- . the rate of procalcitonin remains low in the presence of viral infection. procalcitonin is also a prognostic marker, its elevation is correlated with the severity of the infection, and its decrease is a good indicator of the effectiveness of antibiotic therapy. compliance with ethics regulations: not applicable. rationale: due to induction immunosuppression infection is the most common cause of mortality within the first year after lung transplantation (ltx). the management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. we sent by email a survey to ltx centers around the world dealing with daily clinical vignettes concerning perioperative antibiotic therapy. we considered perioperative period as the period of the transplant surgery (per operative) and the postsurgery time before any infection occurrence (postoperative). after general questions on local practices, we asked each center for colonization definition and their diagnostic methods for microbial screening in recipients and donors. the clinical cases were related to specific issues concerning the management of antibiotic therapy in different clinical situations, including no prior colonization, prior colonization with sensitive or multi-drug resistant (mdr) microorganisms including prior colonization with mdr bacteria not sensitive to beta-lactams. the invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center between june and september . we received a total of responses from countries, mostly from western europe (n = ) and the usa (n = ), (fig. ) . systematic screening for bronchial colonization before ltx was mostly performed with sputum samples ( %), regardless of the underlying lung disease. definition of colonization was very heterogeneous and the delay between the last bacterial isolation in pre-transplant and the ltx to consider if the therapy should target these bacteria varied between week and more than year. in recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin/tazobactam, cefepime, ceftazidime, carbapenems) were reported in % of the centers, and antibiotics with activity against methicillin-resistant staphylococcus aureus (mainly vancomycin) were reported in % of the centers. for these recipients, the duration of antibiotics reported was days ( %) or less ( %) or stopped when cultures of donor and recipients were reported negatives ( %). in recipients with pre-transplant colonization, antibiotics were adapted to the susceptibility of the most resistant strain isolated in pre-transplant samples and given for at least days ( %). conclusion: practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. the antibiotic duration reported was longer for colonized recipients. compliance with ethics regulations: not applicable. the vancomycin was therefore considered as justified or not and appropriate or not. occurrence of nephrotoxicity and supratherapeutic exposure in this study group was compared to critically ill children control group. results: thirty one children receiving vancomycin lines of treatment whose ( %) observed a risk of acute kidney injury (aki) (n = ) and an aki (n = ) during the vancomycin treatment period were included. there was a trend to inversed relationship between plasmatic concentrations of vancomycin and estimated creatinine clearance (r = . ). seven patients observed a nephrotoxicity related to vancomycin, they had a higher plasmatic concentration of vancomycin (p = . ). seven patients ( %) had a supratherapeutic exposure to vancomycin. nephrotoxicity and supratherapeutic exposure were higher in children with or combined liver-kidney transplantation than in comparative critically ill children group. we found blood stream infection due to the central catheter and blood stream infections probably due to the central catheter. one hundred thirtyfive bacteria were identified of which ( %) were staphylococcus coagulase negative. nineteen ( %) lines of vancomycin were appropriate and ( %) were justified. conclusion: vancomycin could have been avoided in one third of children with liver or combined liver-kidney transplantation during the early phase of postoperative stage. vancomycin is associated with a risk of both nephrotoxicity and supratherapeuric exposure. vancomycin should be used with caution, appropriate indications and dosing in this vulnerable population. compliance with ethics regulations: yes. rationale: early bacterial infection is a major and severe complication occurring within the first month after pediatric liver transplantation (lt). the rise of antimicrobial resistance, especially extended-spectrum beta lactamase producing enterobacteriaceae (esbl-pe), is henceforth a concern for these patients. this study aimed to assess the epidemiology of early bacterial infections, including those caused by multidrugresistant (mdr) pathogens, and to identify the risk factors for infection. rationale: the number of cancer patients admitted to emergencies is clearly increasing and digestive oncology is the leading cause of consultation. the aim of this work is to identify the epidemiological factors, the therapeutic modalities as well as the predictive factors of mortality and to compare them with the data of the literature. patients and methods: patients admitted to visceral emergencies for an urgent syndrome revealing or complicating a primary or secondary digestive cancer, and who required immediatemedical and/or surgical intervention and who had stayed at the surgical resuscitation level in our hospital center for a duration of years. several data were entered on excel and analyzed using the spss version software.-epidemiological, concerning age and sex; -clinics including risk factors, history, general condition of the patient and clinical examination data; -para-clinical, interesting biological assessments, and morphological examinations-medical and surgical therapeutics; -postoperative follow-up-treatment results. the three most frequent sites were rated in order of increasing frequency: colo-rectum ( %), pancreas ( %), and stomach ( %). the age group most found was age over years with % of cases, % of patients had under years. this series includes men and women with a sex ratio of , . the installation method was mostly gradual with % of cases. our patients have consulted for urgent clinical presentations mainly occlusive syndrome noted in % of patients. abdominal ct was the first examination performed, followed by abdominal ultrasonography in % and %, respectively. the therapeutic management was medico-surgical. the surgery done in % of patients, % for palliative indication: % were operated for an ostomy discharge, % for a digestive bypass, % for a palliative resection and % for a stoma feeding. postoperative outcomes were % morbidity and % mortality. the main cause of death was septic shock in % of cases, thanks to multivariate statistical analysis three factors were deduced significantly related to mortality: the asa score: p = . ; or = . ; ic: [ . ; . icu and hospital mortality rates were % (n = ) and . % (n = ), respectively. ten patients were alive months after with a median rankin score at [ - ]. more than half of the patients without stupor had a favorable neurological outcome (fig. ) . in univariate analysis, mechanical ventilation and stupor were correlated with mortality, whereas dic and apl were not. by multivariate analysis stupor was the only factor significantly associated with a higher mortality (hr: . [ . - . ] ). conclusion: intracranial hemorrhage is associated with a high mortality rate in al patients, stupor at the onset of intracranial bleeding being independently associated with poor outcome. up to one third of patients will nevertheless survive and experience a favorable neurological outcome. compliance with ethics regulations: yes. neurological outcome assessing by modified rankin scale according to stupor or coma at intracranial hemorrhage diagnosis (blank reflect missing data) rationale: sinusoidal obstruction syndrome (sos, previously known as veno-occlusive disease) is a complication of high dose chemotherapy, frequently occurring during bone marrow transplantation (bmt). severe sos is associated with a high mortality rate, related to multi-organ failure (mof). defibrotide being the only available option for prevention and treatment. prognosis of patients with sos requiring intensive care unit (icu) admission remains unknown. the primary objective was to assess the outcome of these patients. secondary objective was to assess risk factors associated with hospital mortality. patients and methods: retrospective study conducted between january and july in french icus. critically ill adult patients with sos (according to ebmt classification) who received defibrotide were included. results are reported as median [iqr] or number (%). adjusted analysis was performed using cox model. results: seventy-one patients were included with a median age of years . underlying hematologic diseases were acute myeloid leukemia ( %), lymphoma ( %),myelodysplasia/myeloproliferative neoplasm ( %) or acute lymphoid leukemia ( %). sos occurred during myeloablative allogeneic bmt ( %), reduced conditioning allogeneic bmt ( %), autologous bmt ( %) or chemotherapy ( %, including gemtuzumab ozogamycin in patients). median sofa score at icu admission was ]. ebmt prognostic score was often "very severe" ( %). main reasons for icu admission were respiratory failure (n = ), acute renal injury (n = ), shock (n = ), liver failure (n = ), coma (n = ) and monitoring (n = ). median bilirubin level at icu admission was µmol/l [iqr - ] and platelets count g/l . mechanical ventilation (mv), vasopressors, and renal replacement therapy (rrt) were required in % (n = ), % (n = ) and % (n = ) of patients, respectively. sixteen patients receiving defibrotide experienced bleeding events. icu and hospital mortality rates were % and % respectively, mainly related to organ dysfunction. in univariate analysis, delayed defibrotide initiation, bilirubin level, organ supports, sofa, and ebmt scores were associated with hospital mortality. cox model identified older age (hr . , % ci . - . ), mv (hr . , % ci . - . ), rrt (hr . , % ci . - . ), as associated with mortality. prophylactic defibrotide was correlated with a better outcome (hr . , % ci . - . ). similar results were observed after adjustment for center effect. conclusion: when organ support is required, icu management is associated with high mortality. organ support (namely rrt and mv) and older age were associated with poor outcome. prophylactic defibrotide was associated with survival either due to selection process or to efficacy in this setting. additional studies are needed to confirm these results. compliance with ethics regulations: yes. rationale: prognosis of critically ill immunocompromised patients (ciip) has improved over time. neutropenia is common and is found in one third of these patients. prognostic impact of neutropenia remains controversial and little data focus on ciip admitted in a context of acute respiratory failure (arf). primary objective was to assess prognostic impact of neutropenia on outcome of these patients. secondary objective was to assess etiology of arf according to neutropenia. patients and methods: retrospective analysis of prospective multicenter multinational dataset. adults immunocompromized patients with arf were included. adjusted analyses included ( ) a hierarchical model with center as random effect; ( ) propensity score (ps) matched cohort; and ( ) adjusted analysis in the matched cohort. results: overall, patients were included in this study. median age was [iqr - ] and patients ( . %) were of female gender. median sofa score was [ ] [ ] [ ] [ ] [ ] [ ] [ ] and ps was [ ] [ ] [ ] [ ] . main immune defect were hematological malignancy in patients ( %), solid tumor in ( %), systemic disease in ( . %), and other immunosuppressive drugs in ( %). neutropenia at admission was observed in patients ( %). initial oxygenation strategy was oxygen in patients ( %), high flow nasal oxygen in ( %), non-invasive ventilation in ( %) and invasive mechanical ventilation in ( %). before adjustment, hospital mortality was significantly higher in neutropenic patients ( % vs. % in non-neutropenic patients; p = . ). after adjustment for confounder in a mixed model, neutropenia was no longer associated with outcome (or . , % ci . - . ). after ps matching, neutropenic and non-neutropenic patients were compared. hospital mortality was similar in both groups ( % vs. % respectively; p = . ). after adjustment for variables associated with mortality, neutropenia was not associated with hospital mortality (or . , % ci . - . ). arf etiologies were distributed similarly in both neutropenic and non-neutropenic patients (fig. ) , main etiologies being bacterial pneumonia ( % vs. %), invasive fungal infection ( % vs. %), pneumocystis jiroveci pneumonia ( % vs. . %), and undetermined etiology ( % vs. %) (p = . ). conclusion: neutropenia at icu admission is not associated with hospital mortality in this cohort of ciip admitted for arf. surprisingly, arf etiology did not differ despite the multiplicity of observed immune defects. compliance with ethics regulations: yes. rationale: hepatic dysfunction (hd) is commonly observed in patients with hematologic malignancies and associated with an increased mortality in allogeneic hematopoietic stem cell transplantation patients. we aimed to assess incidence, risk factors and prognostic impact of hd in a large multicenter cohort study of critically ill patients with hematologic malignancies. patients and methods: this research was a post hoc analysis of a franco-belgian multicenter prospective study assessing the prognosis of patients with hematologic malignancies admitted to intensive care unit (icu) between january and may . hd was defined as serum total bilirubin ≥ µmol/l at icu admission. for patients with hd, a review of medical hospital records was performed by an expert panel to assess management of hd by attending physicians. results: among the patients with hematologic malignancies admitted to icu, were included in the study, mainly patients with non-hodgkin lymphoma ( . %) or acute myeloid leukemia ( . %). hd at icu admission occurred in patients ( . %). factors independently associated with hd were the use of cyclosporine (or = . , % ci . - . , p < . ) and antimicrobial treatment (or = . , % ci . - . , p = . ) before icu admission, abdominal symptoms at icu admission (or = . , % ci . - . , p < . ), ascites (or = . , % ci . - . , p = . ), hepatic charlson comorbidity (or = . , % ci . - . , p = . ), increased creatinine at icu admission (or = . , % ci - . , p = . ), neutropenia (or = . , % ci . - . , p = . ) and myeloma (or = . , % ci . - . , p = . ). hospital mortality was . % and . % in patients with hd and patients with no hd respectively (p < . ). hd appeared as an independent factor of hospital mortality after adjustment with other organ failure (oradj = . , % ci . - . , p = . ). factors independently associated with hospital mortality among patients with hd at icu admission are reported in table . etiologic diagnoses for hd by physicians were undetermined for patients ( . %) including ( . %) for whom the existence of hd has not even been mentioned in the medical record. investigations were performed in % and only % of patients received a specific treatment for hd. conclusion: hd at icu admission is common, underestimated, poorly investigated, and impairs outcome in critically ill patients with hematologic malignancies. hd should be considered and managed as other organ dysfunctions. it raises the importance of an early severity assessment of hd and a development of diagnosis strategies to get therapeutic options, in close collaboration between hematologists and intensivists. compliance with ethics regulations: yes. rationale: acute respiratory failure (arf) is the main cause for admission to the icu for patients with hematological malignancies (hm). viral pneumonia is poorly described in this population. respiratory viruses pcr is a rapid and sensitive diagnostic tool. thoracic ct allows to guide the diagnosis but is also poorly described. the primary objective was to describe ct features suggesting viral pathogenicity. secondaryobjectives were to assess risk factors associated with the use of invasive mechanical ventilation (imv) and icu mortality. rationale: high-dose methotrexate (hd-mtx) is commonly used in the treatment of solid tumours and hematological malignancies. severe toxicities are frequent, leading to organ dysfunction, multiple organ failure and death. outcome of these patients when critical illness occurs is poorly studied. this study aims to describe mtx-induced toxicities and to assess outcome in critically ill patients. in this retrospective study conducted in the icu of one university hospital between january and december , all the patients who were given hd-mtx (single dose greater than mg/m ) in the icu were included. results are presented as median [interquartile range] and number (percent). results: patients ( men and women) aged years [ - ], were included. b-cell lymphoma had been diagnosed in patients (burkitt, n = ; diffuse large b cell lymphoma with cns (central nervous system) involvement, n = ; primary cns lymphoma, n = ) and t-cell lymphoma in two patients. patients were mainly admitted for coma (n = ; %) or acute kidney injury (n = ; %). mtx was administered at a median dose of . g [ - ] . fourteen patients had concomitant medication interacting with mtx. median mtx clearance was days [ ] [ ] . frequent mtx-related complication were mucositis (n = , %), diarrhea (n = , %) or hepatic failure (n = , %). during icu stay, patients experienced acute kidney injury (kdigo stage . [ ] [ ] ). two patients received carboxypeptidase and three underwent dialysis. overall, patients ( %) required mechanical ventilation, ( %) vasopressors. hospital mortality was % (n = ). cox model identified mtx concentration h after administration higher than . µmol/l as associated with hospital mortality (hr . , % ci . - . ) (fig. ) . conclusion: to our knowledge this is the first study assessing characteristics and outcome of critically ill patients receiving hd-mtx. mtx concentration at h was associated with hospital mortality. despite underlying malignancy, icu support of these patients was associated with a meaningful survival. compliance with ethics regulations: yes. rationale: high-dose methotrexate ( g/m ; hdmtx) is the cornerstone of chemotherapy in acute lymphoblastic leukemia (all) and several high-grade non-hodgkin lymphoma (hnhl). despite standardized prevention, acute kidney injury (aki) and other life-threatening complications still occur. given the cost of glucarpidase, an enzyme that metabolizes mtx in few minutes, and the complexity of hematological patients admitted to the icu, a better comprehensive view of the factors that predict hdmtx toxicity, as well as the role of glucarpidase as rescue therapy in patients with organ failure, is mandatory. patients and methods: retrospective monocenter study including all the adult patients referred for all or hnhl in a french university hospital, and who received hdmtx. aki was defined according to the kdigo classification. univariate analysis (fischer exact or mann-withney tests) followed by multivariate analysis (stepwise logistic regression) were used to identify before hdmtx the clinical and biological predictive factors of aki. outcomes following glucarpidase were also addressed. results: from dec- to sept- , patients received hdmtx (median dose g/m ; all n = , hnhl n = ), totalizing hdmtx pulses. sixty-nine patients ( . %) developed aki after a median time of days (stage n = , stage n = , stage n = including one requiring dialysis in the first week). by multivariate analysis, only age, body mass index and a diagnosis of all were significantly and independently associated with the risk to develop aki. mtx exposure (maximal serum concentration at h - ) was also associated with aki (auc . , p < . ). glucarpidase was used in patients ( %) that differed by a higher age and bmi, and a lower basal egfr. glucarpidase was followed by a rapid renal improvement but serum creatinine did not return to baseline ( vs. micromol/l). thirty patients with aki or delayed mtx elimination did not receive glucarpidase but none required renal replacement therapy and egfr was only slightly but not significantly reduced at the end of follow-up. extra-renal adverse-events (rbc and platelets transfusions, neutropenia, hepatitis, severe diarrhea, mucitis) were more frequent in patients that developed aki. eighteen patients were admitted to the icu, including and that required mechanical ventilation or vasopressor drugs, respectively. conclusion: few actionable factors predict the development of aki after hdmtx, suggesting additional genetic factors. aki was reversed by glucarpidase but progression toward ckd was the rule. further studies will have to identify patients that will actually beneficiate from glucarpidase. compliance with ethics regulations: yes. khaoula ben ismail, sana khedher, ameni khaled, nassereddine foudhaili, mohamed salem usi digestif-service de gastroenterologie-eps charles nicolles.tunis-tunisie., tunisia, tunisia correspondence: khaoula ben ismail (khaoula @hotmail.fr) ann. intensive care , (suppl ):p- rationale: infection is common and accounts for major morbidity and mortality in cirrhosis. patients with cirrhosis are immunocompromised and have increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. we aimed to evaluate the impact of infection on hepatic encephalopathy. patients and methods: this is a prospective study, conducted over a period of years from january to december . consecutive patients with approved decompensated cirrhosis admitted to our department are included. all clinical and biological data were collected from the medical records. univariate and multivariate analysis were used to identify the impact of infection on hepatic encephalopathy. results: a total of patients diagnosed with decompensated cirrhosis were enrolled in this study. mean of age was years ( - ). sex ratio was . . hcv ( %) was the main etiology of cirrhosis. the reasons of hospitalization were: oedema with ascitic syndrome ( % of cases), digestive bleeding ( % of cases), fever ( % of cases), and encephalopathy ( % of cases). patients with infection seemed to have a high incidence of hepatic encephalopathy with % versus % when the patients are none infections. the results also showed that in those with hepatic encephalopathy, an effective antibiotic treatment accelerates significantly wakefulness under h with a rate of % vs. % (p < . ) . in addition, the infection does not influence mortality or length of stay compared to other complications such as digestive bleeding. conclusion: we found that infection caused more episodic hepatic encephalopathy than other complication and an effective antibiotherapy accelerate wakefulness. compliance with ethics regulations: yes. rationale: hepatic encephalopathy (he) is a common cause of hospitalization in patients with cirrhosis. pharmacologic treatment for acute (overt) he has remained the same for decades. to compare polyethylene glycol electrolyte solution (peg) and lactulose treatments in patients with cirrhosis admitted to the hospital for he. we hypothesized that rapid catharsis of the gut using peg may resolve he more effectively than lactulose. patients and methods: this is a prospective study, conducted over a period of years. from janury to december , we have been interested in cirrhotic patients with hepatic encephalopathy. all clinical and biological data were collected from the medical records. univariate and multivariate analysis were used to identify the difference beteween peg and lactulose in the treatement of hepatic encephalopathy. results: a total of patients diagnosed with decompation of cirrhosis were enrolled in this study. mean of age was years ( - ). sex ratio was . . hcv ( %) was the main etiology of cirrhosis. the hospitalization reasons were: edematous-ascitic syndrome in %, gastro-intestinal bleeding %, fever in %, and encephalopathy was present in % of cases. a total of patients were randomized to each treatment arm. baseline clinical features at admission were similar in the groups. twelve of patients in the standard therapy arm ( %) had an improvement of or more in hesa score, thus meeting the primary outcome measure, compared with of evaluated patients receiving peg ( %) (p < . ). the mean ± sd hesa score at h for patients receiving standard therapy changed from . ± . to . ± . compared with a change from . ± . to . ± . for the peg-treated groups (p = . ). the median time for he resolution was days for standard therapy and day for peg (p = . ). adverse events were uncommon, and none wasdefinitely study related. conclusion: we found that peg led to more rapid he resolution than standard therapy, suggesting that peg may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute he. compliance with ethics regulations: yes. acute pancreatitis and pregnancy janati adnane, lina berrada obstetric intensive care unit, casablanca, morocco correspondence: janati adnane (adnanejanati@gmail.com) ann. intensive care , (suppl ):p- rationale: the association of acute pancreatitis and pregnancy is rare but not negligible, it often cause a diagnostic problem given the gravidal context that can lead to serious repercussions. the objective of our study is to assess the particularities in the diagnosis, management and prognosis of acute pancreatitis during pregnancy patients and methods: this is a retrospective study about cases of acute pancreatitis occurred during pregnancy over a -year period ( - ) at the obstetric intensive care unit of the meriem maternity hospital in the chu ibn rochd casablanca. a retrospective analysis of the medical files of these patients was carried out, considering epidemiological and etiological criteria, the treatments administered and maternal/fetal fate. we found cases during this period, with an incidence of / . the average age of onset was years, % of cases occurred in the rd trimester. epigastric pain and vomiting were the common symptomatology. ultrasound showed biliary lithiasis in % of cases with increased pancreas size in % of cases. maternal mortality was zero. uncomplicated benign forms are the most common ( %). severe hypokalemia was found in % of patients. neonatal morbidity was marked by six premature deliveries. among them, a newborn died at day- of life discussion: the association of acute pancreatitis and pregnancy is rare, more frequent during the rd trimester, it mainly affects the young woman. lithiasic biliary pathology remains by far the most frequent etiology. the diagnosis is clinical most often represented by epigastralgia with vomiting and biological via lipasemia and amylasemia dosage. uncomplicated benign forms are the most common. hydroelectrolytic disorders are often found. abdominal ultrasound allows the etiological diagnosis. the treatment is above all symptomatic whose objective is the digestive rest, the correction of the hydroelectrolyte disorders but first of all relieve the pain. conclusion: acute pancreatitis is a rare event in pregnant women, but can have a maternal and fetal prognosis. it must be systematically evoked in front of the acute abdominal pains of the pregnant woman because the confirmation of the diagnosis is easy and the maternal results depend mainly on therapeutic management. prematurity remains the predominant factor in neonatal morbidity. compliance with ethics regulations: not applicable. rationale: aclf is a clinical concept defined in patients with chronic liver disease who presented organ failure(s) secondary to an acute decompensated event. liver transplantation in this indication showed good results in selected patients. the aim of this prospective study was to evaluate the outcome and the factors associated with a favorable selection to liver transplantation in this population. patients and methods: all consecutive patients admitted to the icu with cirrhosis and aclf, were recruited. patient with age < years or with fulminant hepatitis were excluded. results: between july and february , cirrhotic patients were admitted to icu. mean age was . ± . years ( . % male). cirrhosis was due to alcohol in . % of the patients. aclf grading at admission was: . % aclf (n = ), . % aclf (n = ), . % aclf (n = ), and . % aclf (n = ). of the patients, . % (n = ) were considered to be eligible for a transplant project and were assessed for liver transplantation. the main reasons were alcohol abuse ( . %, n = ), death within days after admission ( . %, n = ) and rapid improvement of the liver disease. of the eligible patients, % were transplanted with a mean time between admission to icu and liver transplantation of . ± . days. twelve patients died on the waiting list ( % of the listed patients), mainly of septic shock. among those who were assessed for liver transplantation but not listed (n = ), . % died before the listing (n = ) and . % were not listed because of severe comorbidities (n = ). the global mortality rate was . % (n = ). the and days rate mortality were respectively . % and . %. the overall -month patient survival was respectively % and % in the transplant and non-transplant group (p < . ) for the entire cohort. among eligible patients, factors associated with the absence of liver transplantation, in the multivariate analyses, were mechanical ventilation (hr . , % ci rationale: body composition is known to be a prognostic factor in cirrhotic patients. however, the link between this and the prognosis of patients in intensive care unit (icu) is unknown. the computed tomography offer accurate estimations of muscle mass by analysing a cross-section usually going through the third lumbar vertebrae. this retrospective study aimed to assess the feasibility of body composition (bc) analysis in cirrhotic patients with septic shock, using computed tomography (ct) and evaluate the impact of bc (muscle mass, subcutaneous and visceral fat) on outcome. patients and methods: this retrospective study included cirrhotic patients with septic shock hospitalized in icu who underwent an abdomino pelvic ct scan within h of admission. we collected the surface areas of muscle mass and adipose tissue on the ct scans. we compared bc data with mortality and with the number of organ failures. the average age was years . the average child and meld scores were respectively . [ - ] and . . the prevalence of sarcopenia was %. it was not associated with a higher mortality rate at day (p = . ) or with a higher number of organ failures at day (p = . ). we observed a higher subcutaneous adiposity index in patients who died at day (p = . ) and in patients with renal insufficiency at admission (p = . ). there was a trend (p = . ) towards more visceral fat in patients who died in icu. the assessment by ct of body composition reveal evaluation of bc using ct is feasible and reproducible and may constitute a promising tool to evaluate in cirrhosis critically ill patients. visceral fat mass seems associated with poor outcome in cirrhotic patients with septic shock compliance with ethics regulations: yes. rachid jabi, mohammed bouziane chu mohammed vi, oujda, morocco correspondence: rachid jabi (jabirachid@gmail.com) ann. intensive care , (suppl ):p- rationale: the infection of the necrosis constitutes a pejorative element in the management of the necrotico-haemorrhagic pancreatitis, in the absence of the drainage the mortality approaches %. the morbidity and mortality of surgery can be avoided with minimally invasive treatments. purpose: to compare the morbidity and mortality of the two groups of post-ercp pancreatitis and the other etiologies. patients and methods: a retrospective study over years between and and a comparison between pancreatitis secondary to post-ercp and other etiologies of pancreatitis. a p value of . is considered significant. the surgical treatment used in cases of superinfection post ercp against seven cases of other etiologies of pancreatitis. high mortality in post-ercp pancreatic arm % vs. % (p = . ). high morbidity in the operated group % vs. % (p = . ) represented mainly digestive haemorrhages. duration of stay was significantly longer in the operated group vs. days (p = . ). thrombocytopenia and beta-lactamase-producing enterobacteria have further complicated management in the post-ercp infected pancreatitis arm. the antibiotic resistance of infected pancreatitis in post-ercp patients is . % for ciprofloxacin, . % for imipenem and % for amikacin. conclusion: pancreatitis the most common adverse effect of ercp with significant morbidity and mortality. the collaboration between the intensive care unit gastroenterologist and the surgeon improves management since the risk factors are mainly related to the patient and can not be modified. compliance with ethics regulations: yes. gautier nitel, aghiles hamroun, anne bignon, gilles lebuffe chru lille, lille, france correspondence: gautier nitel (gautier.nitel@gmail.com) ann. intensive care , (suppl ):p- rationale: liver transplantation (lt) has been recently experiencing an expansion of its indications, allowing patients with potentially more co-morbidities to access to transplantation. in our era of graft shortage, we should focus on the identification of the best lt candidates. the aim of our work is to study the determinants of early morbidity and mortality after lt from three angles: occurrence of a major cardiovascular event (mace) or acute renal failure (kdigo stage - aki) in the first days postoperative, and death in the year following lt. retrospective study investigating the occurrence of mace or aki (kdigo - ) within days post-operative and mortality at year after lt, including patients who received a first lt between january and december in our center. analysis of risk factors by a multivariate step-by-step analysis. statistical significance for p < . . data presented in odds ratio (or) rationale: infectious complications are frequently reported in critically ill patients supported by veno-arterial extracorporeal membrane oxygenation (va-ecmo) for refractory cardiogenic shock, but their diagnosis is challenging. no study has specifically studied bloodstream infection (bsi) in this population and some recommendations suggest performing systematic blood culture (bc). in our unit, systematic bc are daily sampled. we investigated the interest of systematic bc to detect bsi under va-ecmo. patients and methods: in a retrospective analysis ( - ), and after exclusion of patients dying within h, all adult patients from cardio-vascular intensive care unit supported by va-ecmo were included. systematic daily and "on demand" bc (at the physician's discretion) performed from va-ecmo implantation to days after withdrawal were analyzed. bsi was defined as at least one bc positive to a pathogen (except for contaminants bsi which required at least two positive bc with the same bacteria in h). multivariable logistic regression was performed to identify risk factors for positivity of systematic bc. rationale: fungal infections are constantly increasing in hospitals. indeed, the increase in these infections and especially candida yeast infections is almost parallel to the increase in the widespread use of a wide range of implanted medical devices such as catheters. for this reason, we have been investigating, isolating and identifying candida yeast colonizing vascular catheters and studying the epidemiological and clinical characteristics of patients with colonized catheters. patients and methods: it is a prospective, transversal study conducted at the intensive care and neurosurgery services of the sétif university hospital, evaluating the fungal colonization of vascular catheters. these are collected from hospitalized patients for a period of months. a culture of the distal end of the catheter is performed directly after its ablation. the results obtained showed that among the samples taken, six are colonized by the yeasts, the incidence is %. six yeast of candida spp were isolated, % of them were candida albicans species, . % candida parapsilosis and . % were candida glabrata. conclusion: it appears that colonization of catheters occurs most frequently in patients with the following characteristics: extreme ages of life, male sex, antibiotic therapy and length of hospitalization or prolonged catheterization. compliance with ethics regulations: yes. rationale: the threat of emergent extensively drug-resistant bacteria (exdr) dissemination worldwide is real. it has become a global public health issue. in fact, glycopeptides-resistant enterococcus faecium (gre) and carbapenemase-producing enterobacteriaceae (cpe) are the lead microorganisms in the high resistant bacteria category. the aim of our study was to characterize the molecular mechanisms and to determinate the antimicrobial susceptibility profiles of gre and cpe isolated from burn patients. patients and methods: prospectively, we studied all cpe and gre strains isolated from burn patients between january and december . all isolated microorganisms were identified on the basis of conventional microbiological techniques. antibiotic susceptibility testing was carried out by the agar disc diffusion method, and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. molecular characterization was performed by multiplex real-time pcr (cepheid, genexpert ® ) allowing detection of the most prevalent carbapenemase encoding genes (blavim, blandm, blaimp, (blaoxa- and blakpc) as well as the genes vana and vanb of gre. results: during the study period, exdr were isolated from burn patients. the most frequent sites of isolation were blood cultures ( %) and skin samples ( . %). cpe represented . % of isolated exdr ( strains). among them, the most frequently identified species was klebsiella pneumoniae ( . %) followed by enterobacter cloacae ( %). twenty-four cpe ( . %) expressed the blandm gene. the blaoxa- gene was found in strains ( . %) and ten strains ( . %) carried both genes. of the cpe, . % revealed ertapenem mic > mg/l whereas most strains were susceptible to imipinem and meropenem with . % and . % of susceptibility, respectively. the antibiotics showing the highest resistance rates were cefotaxime ( . %), piperacillin-tazobactam ( . %), ciprofloxacin ( . %) and amikacin ( . %). the most active agents were colistin and fosfomycin with . % of resistance for each. seven strains of gre were isolated ( . % of exdr). all of them expressed the vana gene, with vancomycin mic > mg/l. however, teicoplanin mics ranged from to mg/l. all gre strains were beta-lactam resistant and highly resistant to aminosides. linezolid and tigecycline were the only active antibiotics. the dissemination of these extensively drug-resistant bacteria must be contained by implementation of strict isolation methods and better hygienic procedures in order to limit their economical and health consequences. compliance with ethics regulations: yes. rationale: stenotrophomonas maltophilia has emerged as an important pathogen that induces nosocomial infections. it is a non-fermentative, gram-negative bacillus that causes severe infectious diseases, particularly bacteremia in the hospital setting. morbidity and mortality due to stenotrophomonas maltophilia seems to be high, particularly in critically ill patient. the aim of this study was to describe the clinical features, management and outcome of patients with stenotrophomonas maltophilia infections. patients and methods: this was a retrospective analysis of prospectively collected data of patients hospitalized in intensive care unit (icu) between january and december . collected data were: age, gender, comorbidities, severity scores on admission, prior infections, use of antibiotics, use of invasive devices (urinary tract catheter, or mechanical ventilation), microbiological data, and antimicrobial therapy and outcome. results: during the study period, patients with stenotrophomonas maltophilia infection were included, with a mean age of ± years. the simplified acute physiology score ii and acute physiology and chronic health evaluation ii on admission were respectively ± and ± . bacteremia caused by stenotrophomonas maltophilia was observed in patients ( %) and ventilator acquired pneumonia in two patients ( %). twenty four episodes were classified as primary bacteraemia and only one as secondary bacteraemia due to urinary infection. four patients ( %) developed septic shock. mean sofa on the day of stenotrophomonas maltophilia infection was ± . prior antibiotic use was observed in % including an antipseudomonal agent in % of cases. infection due to stenotrophomonas maltophilia was considered in cases. empiric antibiotic therapy was administered to patients ( %) and had included an appropriate agent in only five cases ( %). after adapting antibiotics, monotherapy was the choice for six ( %) patients while a combination of two antibiotics was indicated in the others ( %). the most used antibiotic was the colistin in episodes ( %). intensive care mortality was %. univariate comparison between dead and survivors showed a significant difference in prior nosocomial infection and respiratory comorbidities. no independent risk factor of mortality was found in multivariate analysis. rationale: thrombocytopenia is a frequent disorder in critically ill patients, and several studies have reported its correlation with poor prognosis. considering the major role of platelets in hemostasis, a significant drop in platelet count is an alarming sign in septic patients. the aim of this study was to show the relationship between thrombocytopenia and platelet level changes and mortality in septic patients. patients with criteria for septic shock (based on the third international consensus definitions for sepsis and septic shock) at admission or at any time during hospitalization were included in a prospective study conducted for a period of months (january -august , ) in a medical surgical intensive care unit. patients hospitalized for less than h were excluded. thrombocytopenia was defined as a platelet count less than . /mm , and recovery was defined as returning to levels more than . /mm after presenting thrombocytopenia. we assessed the platelet count during the hospitalization and its outcomes. we included patients. the mean ± sd age was . ± . years. sex ratio was . . thrombocytopenia during sepsis (group ) was found in patients ( %) with a mortality rate at %. the mortality rate among patients not showing thrombocytopenia (group ) was significantly lower % (p = . ). the receiver operating characteristic showed that in (group ), a drop in the platelet count (from admission to septic shock day) more than % was associated with poor outcome (sensibility = %, specificity = %, auc = . ). among the (group ), % showed recovered platelet counts. the mortality was significantly higher in the patients with uncovered thrombocytopenia ( % vs. %, p = . ). conclusion: thrombocytopenia was shown to be an indicatorof poor prognosis in our study. in addition, drops of > % and failure to recover the platelet counts were further determinants of unfavorable outcomes. compliance with ethics regulations: yes. mehdi gaddas , sarra dhraief , karim mechri , imen jami , amenallah messaadi , lamia thabet rationale: pseudomonas aeruginosa is known as an opportunistic pathogen frequently causing serious infections. multidrug resistance in this bacterium is increasing worldwide and poses a major problem in the treatment of infections due to this microorganism. analysis of resistance profile to antibiotics of p. aeruginosa helps to establish a prompt control and prevention program. the aim of this study was to evaluate epidemiological profile and antimicrobial resistance of p. aeruginosa isolates in a trauma and burn center. patients and methods: retrospectively, we studied all p. aeruginosa isolates over a -year period (from january to december ). conventional methods were used for identification. antimicrobial susceptibility testing was performed with disk diffusion method and susceptibility results were interpreted using clinical breakpoints according to ca-sfm guidelines. data were analyzed using the sirsystem. minimum inhibitory concentration of colistin was determined using the e-test ® method (biomérieux), then using the eucast broth micro-dilution method (umic, biocentric ® ) since may . results: during study period, non-repetitive strains of p. aeruginosa were isolated, representing % of all isolates. in our center, infections due to p. aeruginosa were endemic with epidemic peaks. p. aeruginosa was mainly isolated from burn intensive care unit ( . %) and anesthesiology department ( . %). the most frequent sites of isolation were skin samples ( . %), blood cultures ( . %), catheters ( . %) and urines ( . %). the survey of antibiotic susceptibility showed high percentage of resistance to the different antibiotics: . % of strains were resistant to ceftazidime, % to ticarcillin, . % to pipercaillin-tazobactam, % to imipenem, . % to ciprofloxacin and % to gentamicin. resistance to colistin was rare. it concerned only four strains, isolated from burn patients. the survey of antibiotic susceptibility evolution have shown a global increase of resistance to commonly prescribed antibiotics between and : from % to . % to imipenem, from . to . % to ticarcillin-clavulanate, from . % to % to ceftazidime and from . to % to gentamicin. whereas ciprofloxacin resistance rate have decreased from . to %. antibiotic resistant strains were mainly isolated from burn intensive care unit, with % of resistance to imipenem and . % to ceftazidime. the dissemination of multidrug-resistant strains of p. aeruginosa in our center must be contained by the implementation of strict isolation methods and better hygienic procedures. compliance with ethics regulations: yes. acinetobacter baumanii: therapeutic impasse sabah benhamza, mohamed lazraq, abdelhak bensaid, youssef miloudi, najib el harrar réanimation de l'hôpital du août, casablanca, morocco correspondence: sabah benhamza (benhamzasabah @gmail.com) ann. intensive care , (suppl ):p- rationale: acinetobacter baumanii (ab) is frequently responsible for nosocomial infection in the intensive care units, and its resistance to antibiotics continues to increase. the objective of our study is to determine the epidemiological profile and antibiotic sensitivity of isolated bacteria in the intensive care unit august , in order to optimize the probabilistic antibiotherapy of bacteremia in intensive care. patients and methods: this is a retrospective study performed in the intensive care unit of the hospital august , , spread over a period of years from january to january . results: the incidence of ab infection in our department was . % for all patients admitted to intensive care. the average age was years ± , male predominance (sex ratio . ). the average time to onset of infection was days. during the study period, ab strains were isolated, % of which were pulmonary, % blood, and % urinary. resistance to c g reached % in , % in and % in . for imipenem resistance was % in , % in , % in . for amikacin, resistance was % in , % in , and % in . for fluoroquinolones resistance was % in , % in and % in . cotrimoxazole resistance was around % in the last years conclusion: the resistance of ab to antibiotics has reached very alarming levels, especially for carbapenems. this requires resuscitators to change their antibiotic prescription behavior and to invest in the prevention of nosocomial infections. compliance with ethics regulations: yes. this is a prospective observational study conducted at the ed during the period of year. data of all patients admitted with suspected infection of any cause were collected. poor outcomes were defined as death and transfer to an icu within h. results: during the study period, a total of patients with a mean age of ± were included. % were male. within h of management in the ed, % of patients were transferred to the icu and % died. independent predictors of icu-transfer and death included low systolic blood pressure, fever and tachycardia. a prediction model containing these independent predictors had a good predictive accuracy with an area under the curve of . ( % ci . - . ). sensitivity was %, specificity %, positive predictive value % and negative predictive value %. conclusion: assessing readily available clinical variables at arrival to the ed can aid in predicting poor outcomes. [ ] [ ] [ ] [ ] [ ] [ ] . the most common co-morbidities were chronic respiratory failure (crf, n = ) and hypertension (n = ). respiratory distress (n = ) and coma (n = ) were the major indications for iv. us diaphragmatic exploration was performed at a median delay of iv at days [ ] [ ] [ ] [ ] [ ] [ ] . % of patients received sedation and . % received neuromuscular blockers. the ventilator mode was control volume in patients via endotracheal tube (n = ) and tracheostomy cannula (n = ). no major incident was detected during the turning of patients. both tid and ted decreased from the sp to the pp (fig. ) : tid (mm) ( in sp vs. . in pp, p = . ), ted (mm) ( . in sp vs. in pp, p = . ). the observed dtf was lower in the pp but without significance ( . vs. . %, p = . ). no difference was showed when the comparison between sp-dtf and pp-dtf was adjusted on the ventilator mode, obesity, neuromuscular blockers and crf. the positioning in pp in ventilated patients reduces both tele-inspiratory and tele-expiratory diameters of the diaphragm but not altered its contractile function. compliance with ethics regulations: yes. significance was considered at p < . . results: results are presented in the table below. discussion: nebuliser type influences the efficiency of aerosol delivery, with the vmn delivering a significantly higher % aerosol dose than the jn at the two circuit positions (p = . on inspiratory limb; p = . at the dry side of humidifier). in agreement with previous reports using bias flow, for both nebulisers, the location within the circuit has a significant effect, with the nebuliser on the dry side of the humidifier delivering more aerosol than on the inspiratory limb (p = . for vmn; p = . for jn). conclusion: for a mechanically ventilated adult tracheotomy patient, the type of nebuliser and the location of the nebuliser within the circuit influences aerosol delivery. rationale: automatic tube compensation (atc) is a mode available in most icu ventilators. it compensates for the resistive pressure into endotracheal tube/tracheostomy canula by continuously providing a pressure assistance based on internal diameter of a new endotracheal tube/tracheostomy tube. its use in icu is unclear. we designed a survey to further explore this. patients and methods: the survey was endorsed by the acute respiratory failure section and the clinicaltrials group of the european society of intensive care medicine (esicm). the pool was sent out via an email on june to the esicm members worldwide. the following closed questions were: country, years in icu, kind of icu, kind of hospitals, kind of respirators, atc use (never, always or in some patients), reasons to or not to use atc, ventilatory mode in which atc was used. the database was frozen on august st after two reminders. we used the gross national income per capita (usd) provided by the world bank to transform the respondent's country into a geographical-economical variable with levels: high-europe, high-noneurope and middle ( ) . atc use was coded as yes or no. the primary end-point was atc rate of use and the hypothesis was that less than % of the respondents do use it. variables were expressed as counts. groups were compared by chi square test. a logistic regression analysis was performed to explore the contributing factors to atc use. we received responses without any doublons, of which six were empty, from countries. four-hundred and nine respondents used atc always or in some patients ( % atc rate of use). this rate was not different between economical-geographical regions, icu, hospitals and years in icu. for those respondents who did not use atc the reasons were: atc mode not available in icu ventilators ( . %), atc not helpful mode ( . %), atc not known ( . %) and atc provides too much pressure assistance ( . %). for those respondents who used atc the reasons were: helpful in weaning ( . %), set by default ( . %) and physiological benefit ( . %). they used atc during spontaneous breathing trial ( . %), with any assisted mode ( . %) and with specific modes ( . %). we found no risk factor for atc use in the logistic regression model (fig. ) . the atc rate of use was unexpectedly high in this survey. this may result from respondents selection bias or from an a priori underestimation of its use. compliance with ethics regulations: yes. rationale: during pressure support ventilation (psv), adjusting the level of assistance mainly aims at maintaining the patient's respiratory effort within a normal range. however, respiratory effort measurement is impeded in clinical routine by the need of esophageal pressure recording. in this study, we evaluated the accuracy of assessing the respiratory effort from the flow and airway pressure signals using several machine learning algorithms based on the equation of motion of the respiratory system. patients and methods: using the asl simulator (ingmar medical) connected to a pb ventilator (medtronic) set in psv, we simulated a massive number of different respiratory cycles. each simulated cycle represented a unique combination of compliance and resistance of the respiratory system, duration and intensity of the muscle pressure (pmus), positive end-expiratory pressure (peep) and pressure support levels. using least squares regression methods, the flow waveform was fitted according to the equation of motion of the respiratory system to determine the compliance and resistance of the respiratory system, and the pmus. the hypothesis used (alone or in combination) to constrain the system were: linearity of pmus at the onset of the inspiratory effort, nullity of pmus at the end of insufflation, and nullity of pmus during expiration. thus, nine methods were built and tested. calculated and actual peak pmus values were compared using the bland-altman method. the nine methods of pmus assessment were evaluated using different simulated cycles. by limiting the analysis to selected cycles with a predefined applicability criterion (intrinsic peep less than cmh o), a limited inspiratory effort (peak pmus less than cmh o) and a high quality of fitting (r > . ), the method using the three hypothesis together to constrain the system was characterized by a bias of . cmh o and limits of agreement of - . and . cmh o. however, when widening the analysis to all the simulated conditions, no method allowed an accurate estimation of the peak pmus : the best one exhibited a bias of - . cmh o and limits of agreement of − . and . cmh o. conclusion: among the nine machine learning methods tested, some provided an accurate estimate of the respiratory effort in selected cycles but none allowed such accuracy across all simulated conditions. this incites to assess automated methods using a more complex physiological and physical model. compliance with ethics regulations: not applicable. rationale: there is a growing interest in esophageal pressure monitoring in mechanically ventilated patients. esophageal pressure can be measured with a specific nasogastric catheter equipped with esophageal balloon and connected to a pressure transducer. it is used as a surrogate for pleural pressure and may be considered as a corner stone in advanced care of ventilated patients to better assess lung and chest wall mechanics and easily detect patient-ventilator asynchronies. however, this promising technique is still seldom used in clinical practice. trained icu nurses may perform oesophageal pressure measurements which may help facilitate its implementation in the usual patient care. this study aimed at assessing whether a specific educational program to train nurses to perform esophageal pressure monitoring allowed reliable measurements. this was a prospective monocenter study performed in an academic icu. written informed consent was obtained from the nurses before inclusion in the study. the specific educational program consisted of a -min online theoretical course, a -h group theoretical teaching and a -min simulation training on a mannequin. then each participating nurse performed three esophageal pressure measurements (using nutrivent ® catheters and an icu monitor connected to arterial line pressure transducers system) on three different mechanically ventilated paralysed patients under supervision. a knowledge assessment was performed with a short written mcq test. the skill evaluation was by two trained experts. concretely the trained nurses performed an esophageal pressure measurement without assistance. their ability to control the esophageal balloon position by an occlusion test, to measure the inspiratory and expiratory airway and transpulmonary pressures and to calculate of respiratory system, lung and chest wall compliances was assessed at the bedside using a standardized evaluation form. we present here the preliminary results of the first nine included nurses. the written knowledge assessment was considered as rationale: several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation. we conducted this study to compare t-piece and pressure support ventilation (psv) ( cmh and peep ) in the process of weaning of mechanical ventilation in burns. patients and methods: it was a prospective randomized trial in burn icu in tunisia during months. mechanically ventilated patients who met standard weaning criteria were included [ ] . patients were randomized into two groups: group under t-piece and group under psv. duration of the test: - min. the tolerance of the vs test should be judged on clinical criteria. stopping the test if occurred: agitation, tachypnea > cycles/ min, tachycardia > / min, spo < %. successful withdrawal was defined as the ability to maintain spontaneous respiration for h after extubation. results: thirty patients were included, randomized into two groups. the mean age was ± years with a ratio sex of . the average tbsa was ± %. the cause of mechanical ventilation was essentially a face neck burned ( %). the following table shows the weaning outcome of both modalities. eighty percent of succeeded extubation for both groups (n = / ). the cause of failure of extubation was secretion retention and clutter in majority of cases followed by neurological and cardiac distress. the duration of mechanical ventilation does not influence the outcome of the weaning test (p < . ), with a mean of duration of ± days. conclusion: our study did not show any difference between the two weaning modalities in the matter of outcome of extubation. the choice of weaning test of mechanical ventilation is to be judged by the clinician according of the state of his patient. compliance with ethics regulations: not applicable. rationale: when expiratory tidal flow does not go up after increasing expiratory driving pressure expiratory flow limitation (efl) occurs. it is thought that efl heralds airway closure (ac). we investigated the role of chest wall elastance (ecw) in both efl and ac in acute respiratory distress syndrome (ards) patients. our hypothesis was that the lower the ecw to lung elastance (el) ratio the higher the likelihood of efl and ac. patients and methods: twenty-five moderate to severe ards patients were prospectively included in two centers. mechanical ventilation was delivered in volume-controlled mode with tidal volume ml/kg predicted body weight at positive end-expiratory pressure cmh o in semi-recumbent position. airway (paw) and esophageal (pes) pressures and flow were continuously recorded during min by a data logger (biopac ). then, end-expiratory and end-inspiratory occlusions were performed for s, then respiratory system was slowly inflated at constant flow. finally, patient was allowed to breathe out freely to atmosphere by using a three-way stop lock by-passing expiratory valve. ac and airway opening pressure (aop) were determined according to chen et al. ( ) . efl was assessed by the atmospheric method ( ) . dynamic elastance of chest wall (edyn,cw) and lung (edyn,l) were obtained from least square linear regression method over consecutive breaths. static elastance (est,cw and est,l) were determined by classic formulas and also by taking into account aop (est,cw_aop and est,l_aop, respectively). the performance of ecw/el ratio to predict efl and ac was assessed by the area under receiver operating characteristic (aucroc) curve. results: efl was observed in patients ( %) and ac in ( %). median aop was . cmh o ( % ci . - . ) . aucrocs for ecw/el ratios to detect efl and ac are shown in table . edyn,cw/edyn,l ratio was better to detect efl than est,cw/est,l ratio with edyn,cw/edyn,l ≤ . % sensitivity and % specificity. correction for aop made the performance of est,cw/est,l ratio as good as that of the edyn ratio. ac was poorly predicted by edyn and est ratios but its prediction greatly improved with aop correction. however, with the est,cw/ est,l_aop the critical ratio was . (sensitivity %, specificity %) and . (sensitivity and specificity %) for predicting efl and ac, respectively. conclusion: efl and ac are frequent in ards at peep cmh o. edyn,cw/edyn,l ratio lower than best predicted efl occurrence. once ac is taken into account est,cw/est,l ratio greater than accurately predicts ac. efl and ac are two distinct phenomena. compliance with ethics regulations: yes. rationale: anesthesia outside the operatingroom (aoor) in a pediatric environment was giving increasingly increasing indications and a lot of progress because of its interest in carrying out diagnostic and/or therapeutic explorations: % of the acts of anesthesia are performed outside the operating room. the objective of our study is: to clarify the importance and the frequency of the practice of the ahbo, to define its particularities, as well as an evaluation of the ratio: benefit/risk in order to reduce the morbidity and mortality. patients and methods: we report in this study the experience of the service of the resuscitation mother-child on the gestures of aoor. this is a prospective observational study, spread over a period of months: from / / to / / , dealing with acts performed for endoscopic digestive and bronchial procedures, cures in dermatology and radiotherapy, and medical imaging (ct and mri). results: of the procedures performed: were performed for ct, for mri, for arteriography and for endoscopic digestive procedures, for bronchoscopies, for radiotherapy treatments, for laser treatments in dermatology. anesthesia techniques use intravenous induction in % of cases using: hypnotics (propofol, midazolam, ketamine), morphine (remifentanyl, fentanyl), inhalation induction in % of cases (sevoflurane, halothane) and curare for cases of bronchoscopy (rocuronium). this anesthesia was marked by the occurrence of accidents in order of frequency: cardiac in % of cases (tachycardia, hypotension and rhythm disorders), and then respiratory in % of cases. the most serious accidents were admitted in reality and are represented by cases, of which required an intubation (bronchoscopy), a case of cardiorespiratory arrest recovered, cases of severe hypoxia associated with bradycardia and which required the ventilation with the mask (radiotherapy), and cases of bronchospasm requiring the deepening of the anesthesia (absence of tci). a good knowledge of the patient and the intervention, and difficulties specific to each specialty is necessary, as well as a preanesthetic consultation. the aoor must obey the same safety rules as in the operating theater and that in terms of: equipment, monitoring (integrate the capnograph to respiratory monitoring whenever deep sedation and when the continuous control of vas is difficult), anesthetic technique (tcbi) and post-procedure wakefulness management that must meet the same requirements as the sspi, especially for prolonged sedation. compliance with ethics regulations: yes. umbilical vein catheterization through wharton's jelly: a possibility for a fast and safe way to deliver treatments in the delivery room? suzanne borrhomée hôpital rené dubos, france correspondence: suzanne borrhomée (suzanne.borrhomee@gmail. com) ann. intensive care , (suppl ):p- rationale: a fast and safe venous access can be a critical issue in the delivery room during neonatal cardiopulmonary resuscitation, or before endotracheal intubation. here, we describe a new method to inject drugs using the umbilical vein, directly punctured through wharton's jelly. this method was performed in newborns between november and may . umbilical vein was identified and punctured easily and a reflux was obtained in all patients. the first step was antisepsis, and then the umbilical vein was punctured. the puncture was made approximately to cm above the navel. after checking for blood reflux, the nurse injected the treatment. the cannula was left in the vein during the injection and removed as soon as the intervention was over (intubation was performed, or the heart rate had increased). results: here, we report ten cases of emergency injection in the delivery room using this method: -four cases of cardiopulmonary resuscitation using this method to deliver epinephrine. cardiac massage was performed on all patients.-six cases of intubations in the delivery room using this method to administer the premedication. in all patients, the umbilical vein was identified easily. the equipment was the one usually used for venous injection in our unit and was manipulated and handled with ease. venous access was obtained in a matter of seconds, and blood reflux was observed in all patients. the treatments were efficient in all but two patients, which was imputable to the method in one patient. discussion: although this method has been known in our nicu for several years, there has been no publication regarding this method in neonates. inserting an umbilical vein catheter in the delivery room has been validated for resuscitation but this technique is lengthy and requires some sterility conditions that makes it even longer, and thus non-fitting for an emergency tracheal intubation. our method is fast and can be performed easily with no specific training. the whole manipulation procedure, from the beginning of the puncture to the end of the flush-out takes to s. we only identified few specific risks related to this method, mostly infectious, and the risk of drug diffusion. we describe a new route for administration of drugs in the delivery room that was successfully used in nine neonates. umbilical vein needle catheterization is not only safe and efficient, but is also fast and easy to perform without any special training. compliance with ethics regulations: yes. rationale: liver transplantation (lt) is the only option for children with end stage liver disease. recent advances in surgical procedure and immunosuppression have permitted a better patient and long term graft survival. however, acute cellular rejection remains a frequent complication occuring in to % of the cases according to different studies. it is more likely to occur during the first weeks post lt. many predictive factors of acute rejection have been described in litterature and results differ from one study to another. pediatric studies regarding this topic are few. the aim of this work is to study acute cellular rejection prevalence in the days following lt and to determine predictive factors. rationale: sedation practices for pediatric magnetic resonance imaging (mri) are highly heterogenous. the main challenge is to keep children immobile while being alone in a traumatizing environment for a long time. clinicians have to ensure hemodynamic and respiratory stability in this isolated environment while minimizing sedation neurologic adverse effects. in this series, we report the potential usefulness, feasibility, efficacy and safety of dexmedetomidine sedation for pediatric mri. patients and methods: a single center retrospective review of six children sedated with dexmedetomidine for mri in an emergency context. all children were hospitalized in the pediatric intensive care unit of a university hospital at the time of mri. results: data on six patients aged months to years is reported. five patients received dexmedetomidine by intravenous route (bolus of - µg/kg over min, followed by a continuous infusion of µg/ kg/h). one child received dexmedetomidine by intranasal route ( µg/ kg with atomization device). one child experienced bradycardia that did not require any intervention. very few movements were recorded during the mris for which images were rated as good quality. conclusion: dexmedetomidine seems a promisingly useful sedation agent for pediatric mri, thanks to its efficient sedative properties and good tolerability without respiratory compromise. compliance with ethics regulations: yes. rationale: computational models, or virtual patients, could be used to teach cardiorespiratory physiology and ventilation, determine optimal ventilation management as well as forecast the effect of various ventilatory support strategies. currently, there is no virtual patient specifically designed for modelling children cardiorespiratory system. thus, our research team has developed a cardiorespiratory simulator for children called "simulresp©". according to summers et al., the quality of a physiologic model is evaluated by three specific criteria: qualitatively, which relates to the model's ability to provide directionally appropriate predictions; quantitatively in steady states and in dynamics, which is the ability of the model to provide accurate predictions in steady state situations as well as dynamic transitions. the purpose of this study was to evaluate the quality ofsimulresp© according to these criteria. this study consisted in a prospective evaluation of the simulresp©'s predictions with simulated healthy subjects. the tests were performed with patients from to years old ( , , , , , years), with different characteristics; gender (m, f) and weight ( th, th and th percentile). blood gas values (ph, pco , po and spo ) were simulated for several virtual healthy patients with different characteristics. this study was conducted for both spontaneously breathing and mechanically ventilated patients. simulresp©'s quality and reliability were evaluated in terms of accuracy, robustness, repeatability and reproducibility. results: simulresp©'s validation procedures are ongoing. we intend simulresp© to be accurate when simulating healthy spontaneously breathing patients. but we hypothezised that simulresp© would not be able to simulate accurate blood gas values of mechanically ventilated patients conclusion: simulresp© is a promising computational model that will serve to perform calibration and validation procedures of clinical decision support systems and help clinican to determine optimal respiratory support strategies at bedside. further calibration procedures are yet required. compliance with ethics regulations: yes. the isthmic surgical tracheostomy, which was performed in the operating room by otolaryngologist under general anesthesia. the cutaneous incision was transversal in all cases.the choice of the cannula was adapted to the age, and the decanulation was carried out according to the evolution of the underlying disease. complications associated with tracheotomy are diverse, and common complications are such as careassociated pneumonia ( . %), tracheostomy tube obstruction ( . %), accidental decannulation ( . %), pneumothorax ( . %) and cases of tracheal stenosis ( . %). the mortality rate amounted to . %, where in most cases was due to the poor prognosis of the underlying diseases. the main factors of evolution are the patient's previous condition, cranial trauma, guillain-barré syndrome, tracheostomy time, prolonged tracheal intubation and the presence of complications. conclusion: regardless of the indication, the tracheotomy is an act of survival whose usefulness and effectiveness are certain. rationale: aspiration pneumonia (ap) is a frequently suspected complication of drug overdose requiring mechanical ventilation (mv) and admission to intensive care unit (icu). in the absence of reliable biomarkers for distinguishing between aspiration pneumonia and aspiration pneumonitis, antibiotic therapy is frequently prescribed. latest studies suggest that a care protocol could better select patients requiring antibiotic therapy. the objective was to determine the impact of a care protocol on the antibiotic prescription among patient admitted to icu for toxic coma with mv. we conducted a prospective observational cohort study in four icu. we included all patients admitted for toxic coma with mv. in the university-affiliated icu, a care protocol was applied. in the three others icu, physicians declared that they did not follow formalized conduct within the service and did as usual. results: we included patients in care protocol group and in control group. the mean saps ii was . (± . ) with a mean glasgow coma scale score at . (± . ) before intubation. within the total population, patients ( %) had a pulmonary bacteriologic sample (pbs), mostly because purulent tracheobronchial aspirate and new infiltrates on the chest x-ray (respectively . % and . % of the population with a bacteriological sample). among the patients with a bacteriological sample, ( %) were culture positive. the incidence of probabilistic antibiotherapy did not differ between the care protocol group (n = ) and the control group (n = ) . there was no difference for the incidence of pbs ( in each group). the others secondary outcomes did not differ either (table ) . conclusion: our study does not show that a care protocol allows a reduction of antibiotic prescription among patient admitted to icu for toxic coma with mv. our incidence of antibiotic prescription is lower than the previous studies. the absence of difference can be explain by two reasons: some of the physicians of the control group had been trained in the university-affiliated icu in the last years and may follow a management approach similar to that of the control group; despite our precautions, the existence of the study could have modify the practices in the control group. compliance with ethics regulations: yes. rationale: pancreatic surgery is associated with high morbidity, mostly due to infectious complications, so that many centers introduce post-operative antibiotics for all patients. such systematic prescriptions are not consensual and often rely on local practices. the aims of the study were to describe the occurrence of surgical site infection (ssi) and the antibiotic (atb) prescription after pancreatic surgery, and to determine the risk factors of post-operative surgical site infection, in order to better define the clinical indications for the prescription of antibiotics after major pancreatic surgery. patients and methods: all patients undergoing a scheduled major pancreatic surgery from january to november were included in the study. patients were classified in four groups according to the occurrence of a surgical site infection and to the post-operative antibiotic prescription as follows (ssi+/atb+; ssi-/atb+; ssi+/atb-, ssi-/ atb-). in addition, risk factors (fever and pre-operative biliary prosthesis) associated with the occurrence of a surgical site infection and with the antibiotic prescription, were analyzed using a logistic regression model. results: data from patients ( pancreaticoduodenectomies and splenopancreatectomies) were analyzed and classified as presented in the table. thirty patients ( . %) experienced a surgical site infection and ( . %) received post-operative antibiotics. we did not find any difference on post-operative antibiotic prescriptions ( . % versus . %, p = . ) between patients who developed a surgical site infection and those who did not. amongst the patients who were not prescribed antibiotics post-operatively, ( . %) did not develop a surgical site infection while ( . %) did. in-icu mortality did not differ between infected and non-infected patients ( versus %, p = . ). post-operative fever was different between ssi+ and ssi-( . versus . %, p < . ), while the prevalence of pre-operative biliary prosthesis was similar ( . versus . %, p = . ). amongst patients who did not develop a surgical site infection, antibiotic prescription was not associated with fever (p = ), but associated with a higher prevalence of preoperative biliary prosthesis ( . versus . %, p = . ). conclusion: non-systematic antibiotic prescription after major pancreatic surgery allowed to appropriately spare antibiotics in ( %) patients at the cost of under prescription in ( . %) patients. these results suggest that systematic post-operative antibiotic prescription could be excessive. fever appears to be a relevant clinical sign for individual-based prescription, whereas the presence of a biliary prosthesis does not. compliance with ethics regulations: yes. ( , ) . however, there is little evidence to support those recommendations ( ) . we aimed to describe care paths of pm with sepsis in french hospitals and to assess outcomes depending on their hospital trajectory. we conducted a retrospective analysis of the french medico administrative (pmsi) database of consecutive patients with pm and sepsis admitted to french hospitals, between and . only the first hospital admission was considered. cases were identified using a combination of a diagnosis code for pm plus a diagnosis code for organ failure or a procedure code for organ support. hospital trajectories were determined from the first admission to death or discharge, taking into account all potential transfers. costs and endpoints were determined at the end of patients' trajectories. five groups of patients were defined, according to care pathways: direct icu admission ( sticu); secondary icu admission, after initial admission to another unit including wards (ward ndicu) rationale: new-onset atrial fibrillation (af) is a common complication in patients with sepsis and is associated with increased mortality and morbidity rates. this condition results from a complex chain of events in response to infection, involving immunologic, humoral and cellular process and sympathetic overactivity. landiolol, the new injectable beta-blocker, with high beta selectivity and minimal impact on arterial blood pressure, may have beneficial effects in such a context. in this study, we aimed to investigate whether landiolol decrease the newonset of atrial fibrillation in a mice model of endotoxin-induced sepsis. patients and methods: thirty c bl/ male mice were randomly allocated to the following groups: sham (administration of µl of isotonic saline intraperitoneally-ip), septic (administration of µl of isotonic saline with mg/kg of lipopolysaccharide-lps-of e. coli o :b ip) and septic + landiolol (administration of isotonic saline with mg/kg of lps and, two hours later mg/kg of landiolol ip). four hours later, an attempt of af occurrence was triggered by a transesophageal electric pacing at fixed rate (as previously reported) in all mice previously anesthetized by isoflurane %. ekg was continuously recorded. results: ten mice per group (mean weight: ± g) have been included and analyzed. among the sham group the mean heart rate was at bpm versus bpm in the septic group. among the septic + landiolol group the mean heart rate was at bpm (p < , ). after transesophageal stimulation, none mice in the sham group had af, seven mice ( %) in the septic group had an af, and mice ( %) in the septic + landiolol group had an af. landiolol decreased the incidence of new-onset, sepsis-induced atrial fibrillation in mice (p = . ). conclusion: landiolol seems to have a protective effect against sepsis-induced af in mice. however, the mechanisms, including sympathetic activation and inflammasome pathways, should be investigated before drawn definitive conclusion regarding to efficiency of landiolol to prevent new-onset af during sepsis. compliance with ethics regulations: yes. - mg/l at or h, proportion of patients with a vancomycin serum concentration < mg/l, previously associated with resistance emergence and assessment of mortality and test of cure. results: a serum vancomycin concentration between - mg/l was reported in out of included patients ( %). a serum vancomycin concentration < ml/l and > mg/l were reported in patients ( %) and patients ( %), respectively. vancomycin serum concentrations during follow-up are shown in fig. . in multivariate regression analysis, a longer time between admission and initiation of vancomycin was the only parameter associated with a serum vancomycin out of this target, while acute kidney injury (aki) was associated with a lower incidence of subtherapeutic concentration. acute kidney injury rate was significantly higher in patients with a serum vancomycin concentration > mg/l. discussion: an adequate therapeutic target of serum vancomycin concentration was reached in % patients with nearly % < mg/l, which was similar to previous studies. aki and rrt requirement were higher in patients with serum vancomycin concentration > mg/l, whereas it is hardly to know whether it is a cause or a consequence. conclusion: these findings highlight the importance of a larger loading dose, vancomycin monitoring and measured creatinin clearance to improve vancomycin dosing protocol. compliance with ethics regulations: yes. rationale: suicide is a global phenomenon and one of the leading causes of death in the world. tunisia ranks second in the suicide rate in the maghreb, with . cases of suicide per , inhabitants. the aim of this study was to reconstruct the state of suicidal subjects before the act in order to identify their psychiatric profile. patients and methods: a -year prospective observational singlecenter ( -bed intensive care unit) study including all patients hospitalized for suicide attempt (sa). psychiatric evaluation of patients and contact with their families were done before intensive care unit discharge. results: seventy-one patients were enrolled with female predominance (sex ratio . ). mean age was ± years. familial or personal history of mental illness were found in ( %) and cases ( %) respectively. personal mental disorders were depression ( %), bipolar disorder ( %), schizophrenia ( %) and border line personality disorder ( %). twenty-five per cent had prior sa. sixty-three per cent were single, % married and % divorced. the common methods of suicide included drug ( %), chloralose ( %) and pesticide ( %) poisoning. mean igs ii and apache ii scores were ± and ± respectively. on admission, % of all patients were in coma, % had shock and % developed aspiration pneumonia. mechanically ventilation was done in % of all cases with mean duration of days. the mean length of stay in intensive care unit was days. mortality rate was %. psychiatric evaluation and contact with families deduced that the main precipitating factors for suicide were traumatic events. in fact: relationship problems (familial, marital or breakups), school failure and mourning were found in %, % and % of all cases respectively. reactional sa accounted for %. rationale: poisoning is a worldwide problem, associated with high morbidity and moratlity. in tunisia, the rate of fatal poisoning has been increasing in the last years, with emergence of new toxic substances. regardless of the toxic, fatal poisining is considered as a non natural death, that requires medico-legal investigation, to assess whether it is suicidial, crimnal or accidental death. this study aimes to determine the epidemiological characteristics of the cases of fatal poisoning in south, to identify the toxics used in oder to deduce the preventive measures. patients and methods: we conducted a retrospective study of all cases of fatal poisoning recorded in the forensic department of habib bourguiba university hospital in sfax, tunisia, over a -years period ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . results: during the study period, cases of fatal poisoning were autopsied. the number of victims recorded per year varied between and cases with an average of cases per year. the average age was years with extrems ranging from months to years. nearly half ( . %) were younger than years. a male predominance was noted with a sex-ratio of . . the majority of victims were single, loweducated and from rural origin. personal antecedent of psychiatric pathology was found in . % of cases. psychotic disorders (schizophrenia) and depression were the most common pathologies. in our study we noticed that death occured every weekday without significant difference between days. however, the frequency of fatal poisoning was slightly higher in cold seassons ( . %). in . % of cases, victims were found dead at home. accidental fatal poisoning was the most common ( %). no criminal cases have been observed. we noted a male predominance in accidental forms and a female predominance in suicidal forms. carbon monoxide poisoning was the most common ( cases) followed by the organophosphorus poisoning which was noted in cases. conclusion: decreasing the mortality rate from poison ingestion requires increasing public awareness about poisons and improving emergency service equipment and health personnel training. compliance with ethics regulations: yes. severe acute poisoning by organophosphate pesticides: report of cases at the oran hospital and university center mourad goulmane hospital and university center of oran, oran, algeria correspondence: mourad goulmane (goulmane.mourad@univ-oran . dz) ann.intensive care , (suppl ):p- rationale: organophosphate pesticides are synthetic organic pesticides widely used in agriculture mainly as an insecticide, nemacid or acaricide. these are the agricultural products, the most incriminated in poisoning in our context. the objective of this work was to determine the clinical, paraclinical, and progressive characteristics of this poisoning in a resuscitation environment. patients and methods: retrospective study of cases admitted to intensive care (january -december ). inclusion criteria were clinical, para-clinical, therapeutic and progressive. results: cases were identified: women and men, mean age = . ± years. the suicide attempt was the main reason for the intoxication ( cases). the glasgow coma score averaged ± . the central syndrome was present in % of our patients, followed by muscarinic syndrome % and nicotinic syndrome in % of cases. therapeutic management consisted of mechanical ventilation in % of cases, the use of vasoactive drugs in % of cases and the administration of antidotal treatment in % of cases. the overall mortality was . %. conclusion: organophosphate pesticides intoxication is a real health problem in algeria. it is a serious condition dominated by the respiratory and neurological distress that causes most deaths. it concerns in our context especially young women who ingest the product for the purpose of autolysis. the diagnosis is based on the clinical and dosage of cholinesterase activity in the plasma. treatment combines symptomatic measures that rely primarily on respiratory and neurological resuscitation to antidotal treatment. the clinical course in this type of intoxication is generally favorable under treatment with regression of signs in a few days. mortality is high in our context, so it should be considered a diagnostic and therapeutic emergency. the commercial availability of these products is worrisome, justifying the use of a broad prevention program to inform the public and authorities of the danger of organophosphate pesticides compliance with ethics regulations: not applicable. . the clinical examination revealed that five patients met the criteria for serious intoxication with the following signs: coma in four patients requiring the use of mechanical ventilation, seizures (n = ), rhabdomyolysis (n = ), shock (n = ), toxic takotsubo (n = ) and hepatocellular failure (n = ) leading to patient's death. the use of mechanical ventilation was necessary in patients. the analysis of the severity factors did not show a statistically significant association between severity, age (p = . ), sex (p = ) and chronic consumption of psychoactive substances (p = . ). on the other hand, we did not find a statistically significant association between serious intoxication, the number of tablets ingested (p = . ), the apacheii score (p = . ) and the average length of stay (p = . ). conclusion: ecstasy acute poisoning is becoming more common in our country and can potentially be very serious regardless of age, sex, medical history or number of tablets ingested. on the other hand, the concentration of nmda could be the only factor to be taken into consideration upon admission. compliance with ethics regulations: yes. quarter of early trauma-related mortality, in some series. early identification of poor outcome predictors could be valuable to guide the most appropriate care. we aim to determine factors associated to mortality in patients with severe non-penetrating chest trauma admitted to the icu. patients and methods: this is a prospective cohort study, including all patients with isolated severe blunt chest trauma (abbreviated injury scale ais > ) admitted to the intensive care unit of a university hospital, over a one-year period. the primary objective was to analyse risk factors associated to death and poor outcome using univariate and multivariate analysis. results: one hundred-thirty patients were admitted to the icu for blunt chest trauma among them were diagnosed with severe isolated chest trauma and were included. the mean age was at ± , mean iss at ± and mean tts at ± . twenty-eight ( %) patients were diagnosed with acute respiratory distress syndrome, ( %) with post-traumatic acute kidney injury and fourteen ( %) with post-traumatic pulmonary embolism. the mean length of icu stay (los) was at ± days and mean number of days on ventilator was at ± days. thirty-two ( %) patients underwent elective tracheostomy for prolonged intubation. thirty-seven patients ( %) developed infections, among them thirty ( %) were diagnosed with pulmonary infection and seven ( %) with non-thoracic infections. overall mortality had an incidence of . % ( patients rationale: early hyperglycaemia in traumatic brain injury (tbi) is a part of the stress response. it is an important indicator of severity and a reliable predictor of prognosis. we aimed to describe the epidemiological, clinical and paraclinical characteristics and to assess the prognostic impact of this hyperglycaemia on the tbi. we conducted a retrospective study in the intensive care unit (icu) of our hospital between and . were included all patients with tbi and blood glucose > mmol/l at the first h post-trauma. results: during the study period, patients were hospitalized in our icu with tbi. early hyperglycemia (> mmol / l) was found in patients ( . %). in univariate analysis, glycaemia > . mmol/l (= mg/dl) at admission was significantly associated with mortality (p = . ). we observed that glycaemia > . mmol/l at h , > . mmol/l at h , > . mmol/l at h and > . mmol/l at h was significantly associated with mortality (p = . ; p < . ; p = . and p = . , respectively). the risk factors significantly associated with mortality were age > years (p < . ), saps ii > (p < . ), initial shock (p < . ), glasgow coma scale (gcs) < / (p < . ), coma period > days (p = . ). the ct scan lesions statistically associated with mortality were: subdural hematoma (p < . ), cerebral oedema (p < . ), intra cerebral haemorrhage (p = . ), cortical contusion (p = . ), contusion of cerebral trunk (p = . ), contusion of the corpus callosum (p = . ), thalamus contusion (p = . ). in multivariate analysis, independent risk factors statistically associated with mortality were age > years old (or = . ic [ . - . ]; (p = . )), glycaemia > . mmol/l at admission (or = . ic [ . - . ]; (p = . )),gcs < / (or = . ic [ . - . ]; p < . ), intracerebral hematoma (or = . ic [ . - . ]; p = . ). we recommend a mandatory control of the blood glucose levels during a tbi with a target between . and . mmol/l in the acute phase. compliance with ethics regulations: not applicable. the fat embolism syndrome (fes) is a set of clinical, biological and radiological signs resulting in the obstruction of microcirculation by micro-droplets of insoluble fats.the clinical signs of the fes are not very specific, the diagnosis is difficult and the risk of misunderstanding this syndrome is very real.the fes appears after a trauma, often few days later. however, it sometimes occurs without previous trauma; and it is particularly difficult to recognize in these cases. the aim of this work is to define the epidemiological profile, the clinical and para-clinical features of this syndrome and its therapeutic management. rationale: sedative and analgesic treatment administered to critically ill patients with mechanical ventilation need to beregularly assessed to ovoid complications of oversedation mainly in elderly patients. our objective is to evaluate our sedation practice in the elderlyin our unit patients and methods: it was a prospective observational study, including elderly patients over years of age without acute brain injury requiring sedation more than h of hospitalization in the intensive care unit of our university hospital between april and december . thirty patients were included. the aged was . years, the sex ratio was . . respiratory distress was the most common reason for hospitalization %. the most accepted diagnoses were the decompensation of copd in % of cases and septic shock in % of cases. the saps ii averaged ± points, sofa averaged ± . points. renal failure was found in patients ( %), hepatic impairment was noted in patients ( %), hypoproteinemia was marked in patients ( %). midazolam was used in % of patients. it was in combination with fentanyl in % of cases and remifentanyl in % of cases. the median ramsay score . ± . on the first day of sedation and . ± . on the second day of sedation. the median rass scale was − . ± . on the first day of sedation and − . ± . on the second day of sedation. the median bps scale . ± . on the first day of sedation and . ± . on the second day of sedation. the mean wake up time was ± , days. neuromyopathy of resuscitation was suspected in seven patients ( %), withdrawal syndrome was observed in two patients ( %) and acute cognitive dysfunction in two patients ( %). the median duration of sedation was . days ± . days, the median duration of mechanical ventilation was . ± . days, the median length of stay was . ± . days. ventilator-associated pneumonia was diagnosis among % of patients. the mortality in intensive care was %. conclusion: sedation analgesia in the elderly person should be adapted according to age, ideal weight and renal and hepatic function by decreasing the initial doses. it should be evaluated by the recommended scores by setting a sedation objective according to the pathology. compliance with ethics regulations: not applicable. rationale: more than original articles are newly indexed in pub-med every day. journal club (jc) is one way to cope with this abyssal amount of medical information. we aimed at ( ) describing journals and articles analyzed during our jc sessions ( ), reporting the proportion of published articles being analyzed during jc sessions and ( ) assessing the clinical impact on our daily practices for each journal. patients and methods: a retrospective analysis of prospectively collected data over a -year period from to in a universityaffiliated icu. jc sessions were scheduled weekly and participants were free to choose and expose orally an article recently published in any medical journal (general, icu or non-icu specialized). clinical impact of a journal was retrospectively and independently assessed by two attending intensivists (dc, hm) and was defined by the ratio of articles considered as having a direct impact on our daily practices over the number of articles of the same journal read during the same period. results: from august to august , jc sessions were held and articles-mostly original (n = / ; %)-from journals were analyzed, accounting for . % of the articles ( . % of the original articles) referenced in pubmed during the same period. median number of articles exposed per session was [ ] [ ] [ ] [ ] . median number of doctors attending each session was [ ] [ ] [ ] (attendings: [ ] [ ] , fellows: [ ] [ ] , residents: [ ] [ ] ). general, icu and non-icu specialized journals accounted for %, % and % of the exposed articles, respectively. most of the reported articles dealt with intensive care (n = , %) especially infectious diseases (n = / ; %), hemodynamics (n = / ; %) or icu-organization (n = / ; %). compared to general and non-icu specialized journals, the proportion of read-over-published articles was higher for icu-specialized journals ( . % vs. . % vs. . %, respectively; p < . ). among original articles, only ( . %) [interventional (n = / ; %); observational (n = / ; %) studies] were considered as having a clinical impact on our daily practices. compared to icu and non-icu specialized journals, general journals had a higher clinical impact ( . % vs. . % vs. . %, respectively; p = . ). data regarding the most read general, icu and non-icu specialized journals are detailed in table . in a french university-affiliated icu with regular jc sessions, the proportion of read-over-published articles and the clinical impact of medical journals appear minor. in the ocean of medical literature, general medical journals appear more worth reading by intensivists than icu-specialized journals. compliance with ethics regulations: yes. rationale: the world's population is aging and the and over's age group is growing fast (+ . % per year). this aging population is impacting intensive care units with exponential rates of elderly patients ( . % in , % in ) , associated with significant mortality (from % to %). the evolution and the prognostic factors of these elderly patients in intensive care are therefore a public health issue for optimal management. patients and methods: we included all patients aged and over who were operated and admitted to surgical resuscitation in our center, with a duration of stay greater than h, from april to july . the data collected were: general characteristics of this population, mortality in intensive care, at day and at months and the prognostic factors guiding their evolution in intensive care and at months. results: of the patients included in our study, mortality was . % in intensive care, . % at day and . % at months. the prognostic factors in the intensive care unit were the average dose of noradrenaline at day (threshold at . mg/h), the sofa score at day (threshold at points) and the igs score (threshold at points). the prognostic factors at months were ventilatory autonomy on day (spontaneous ventilation, non-invasive ventilation, invasive ventilation), the reason for admission to intensive care (acute respiratory distress or septic shock) and the fragility score (clinical failure scale with a threshold at ). conclusion: the mortality of patients aged and over is influenced by prognostic factors easily obtained daily at patient's bed. these prognostic factors could be an aid for the resuscitation teams to evaluate the relevance of the care undertaken in elderly or even very elderly patients admitted in an acute situation. compliance with ethics regulations: not applicable. assessing patient safety culture perception in the intensive care unit in tunisia oussama jaoued, chaoueh sabrina, sik ali habiba, wael chemli, gharbi rim, fekih hassen mohamed, elatrous souheil hôpital taher sfar, mahdia, tunisia correspondence: oussama jaoued (oussamajaoued@gmail.com) ann. intensive care , (suppl ):p- rationale: in tunisia health care system, patient safety has become a priority of quality assessment. the aim of our study was to describe the safety culture perception of the intensive care unit staff. patients and methods: the safety attitude questionnaire (saq-icu) was distributed to all intensive care unit staff by email. the questionnaire explores safety culture domains: "team work", "safety climate", "job satisfaction", "stress recognition", "perception of the hospital and intensive care unit management" and "work condition". results: eighty participants responded to the questionnaire, % of them were women. participants were doctors in . %. the coordination between physicians and nurses was very good only in %. thirtynine participants thought that the workload was high and % like their work. medical errors are handled appropriately in % of cases and it was difficult to discuss errors in % of cases. the hospital is a good place to work in % of participants, % of participants were less effective at work when there were tired. the hospital did a good effort of training new personal in % of cases. the number of medical staff was lower than expected in % of cases. half of participants would feel safe being treated as patients in their respective units. all domains explored by saq-icu could be improved according to attendants. conclusion: safety culture perception among intensive care unit staff had several deficiencies, mainly the working conditions, the ignorance of medical error reporting procedures and the lack of communication. rationale: the simplified acute physiology score ii (saps ii) is an icu scoring system used to predict the mortality risk in patients presenting at the icu. however the majority of critically ill patients present initially at the ed and their transfer to the icu may be delayed for hours. therefore, the ability to accurately assess mortality risk at ed may have a great impact. the purpose of this study was to evaluate the performance of saps ii in predicting early and late mortality in ed patients. patients and methods: this prospective study was conducted at the ed during a -month period. data for adult ed patients were evaluated. saps ii score was used to predict early and late mortality rates at -h and -day respectively. discrimination was evaluated by calculating the area under the receiver operating characteristic curve (auroc). results: during the study period patients were enrolled. the mean age was ± years, % of the patients were men. the mean saps ii was . the early mortality rate was % and late mortality rate was %. saps ii was efficient in predicting early mortality, with an auroc of . ( % ci . - . ). however, it demonstrated no value in predicting late mortality with an auroc of . ( % ci . - . ) conclusion: in this study, saps ii score was accurate in predicting early mortality, however this tool appears less suitable for predicting late mortality. compliance with ethics regulations: yes. oussama jaoued, chaoueh sabrina, sik ali habiba, yosri ben ali, fekih hassen mohamed, elatrous souheil hôpital taher sfar, mahdia, tunisia correspondence: oussama jaoued (oussamajaoued@gmail.com) ann. intensive care , (suppl ):p- rationale: the aging of the population increased the number of hospitalizations in icu. the aim of our study was to determine the impact of hospitalization of patients over the age of on morbi-mortality and consumption of care (omega score). patients and methods: this is a retrospective study carried out in the icu in the hospital of taher sfar in mahdia over a period of years. all patients hospitalized in the icu were included in this study. two groups of patients were individualized: g : patients over years old, g : patients under years old. results: during the study period, patients ( < years old and ≥ years old) with a mean age ± years and with a mean sapsii ± were included. the common reason for hospitalization was acute respiratory failure in % of cases. comparing the two groups, the severity score sapsii was higher among patients older than years ( ± vs ± , p < . ). the use of mechanical ventilation was more common in the first group ( % vs. %, p < . ). the incidence of nosocomial infections was similar in both groups ( % in the group g and % in group g , p = . ) and the use of renal replacement therapy was also similar in tow groups ( % in the g group and % in the g group, p = . ). the duration of mechanical ventilation and length of stay were similar between the two groups. workload evaluated by the omega score was higher in the first group ( rationale: icu outcome depends on quality of pre-icu care. we aimed to assess the chain of care of deteriorating ward patients (dwp), through evaluation of preadmission severity and delays before admission, and association with outcome. patients and methods: retrospective observational study in a single center ( beds general hospital) for year-may th of to . all adult patients admitted in the icu from the wards were included, except for scheduled surgery, or unexpected event in the operative theater. preadmission severity was assessed through levels of national early warning score (news ): group with news inferior to , group with news between and , and group with news superior to . these scores were established from vital signs during the h before icu admission. patterns of patients, including sofa and saps , knaus index, charlson comorbidity score, cause of admission and technics used in the icu, length of stay in the icu and in the hospital, limitations of life-supporting care, and mortality at and days after icu stay. satistical analysis was performed through chi and fisher tests on qualitative parameters, and with kruskal-wallis, student and mann-whitney tests for quantitave data. results: sixty-eight patients were studied: in group , in group and in group . most patients (all except ) had not respiratory rate monitoring before icu admission. icu mortality was associated with rising preadmission severity (group : . %; group : . %; group : . %). base patterns (charlson comorbidity score, knaus index) did not differ between the groups, and . % of patients presented with sepsis. main causes of admission were respiratory ( . %), hemodynamic ( %) or neurologic ( . %) failures. all patients admitted after cardiac arrest resuscitation ( patients) belonged to group . acute severity scores (sofa and saps ) followed preadmission severity. limitation or withdrawing of life support in the icu was higher in group ( . %) than in groups ( %) and ( . %) . median delay between first news equal or superior to and icu admission was h, and h between news equal or superior to . diffrences in delays were not associated with outcome. discussion: our study outlines weaknesses in the chain of care of dwp. emphasis should be put on respiratory rate monitoring and better assessment of severity. rationale: access to critical care is controversial in older patients for reasons: lack of available icu-beds and speculation on induced costs. in contrast, admission of young patients aged or under is infrequently questioned even though they develop catastrophic multiple-organ failure requiring full care. in addition, emotive reaction triggered in staff by these patients often represents a heavy psychological burden when icu-stay is < h. information on the epidemiology, clinical information and induced costs regarding such patients is lacking. patients and methods: this study retrospectively assessed the records of patients aged or under, and admitted from january to august . cost-related expenses charged to care-payers were obtained from our medical information department. data (number, percentages or medians) were reported and discussed by comparison with those of nonagenarians during the same period. results: of , icu-admissions, were aged or under ( %), of whom ( . %) died within the icu, with ( %) dying within h of admission despite full intensive care. the latter represent our study population ( . % of the screened population). the median age was . years , male gender was prevalent ( %). half the patients (n = , %) were referred from the emergency department, ( . %) from hematology, from oncology ( . %), from medical intermediate care units ( . %), and one from digestive surgery ( . %). the first diagnosis at admission was septic shock (n = , . %), followed by post-anoxic encephalopathy (n = , . %), coma (n = , . %), acute respiratory failure (n = , . %) and cardiogenic shock (n = , . %). sapsii was . all patients were ventilated and infused norepinephrine. two patients underwent ecmo, and others mars. mean (± sem) retribution per stay was , ± €, and mean retribution per "day of stay" €. discussion: full care of these icu-patients, with early mortality has a financial impact similar to that of nonagenarians at , ± , €; the cost per "day of stay" is therefore on average % higher than that of nonagerians (mean length of stay: . days), and, in our experience, % higher than that of average patients. conclusion: icu-patients aged or under represent a small percentage of admissions and display half our overall mortality: one third of them die within h of admission with a not insignificant financial impact for cost-payers. septic shock is the first cause of referral, followed by unexpected cardiac arrest. compliance with ethics regulations: yes. rationale: severity scores in patients with sepsis are useful for triaging and predicting mortality. mortality in emergency department sepsis (meds) score is validated in patients with sepsis in the emergency department. curb- is validated in patients with communityacquired pneumonia but not in sepsis. curb- is a simple bedside tool that has many common elements with new sepsis identification score-q sofa. the study aimed to assess the accuracy of curb- score in predicting icu admittance and mortality compared to meds score. patients and methods: this prospective study was conducted at the ed during a -month period. we enrolled all adult patients with sepsis admitted to the ed. meds and the curb- scores were calculated at admission. patients were studied using curb- score and their icu admission and in-hospital mortality were ascertained. results: a total of patients were enrolled. the mean age was ± years. % of the patients were men. % of patients had a curb- score ≥ points with a mean meds score of %. among these patients, % were admitted to icu and % died. the curb- score,was efficient in predicting both icu admittance and in-hospital mortality with an auroc of . ( % ci . - . ) and . ( % ci . - . ), respectively. conclusion: a higher curb- score was correlated with higher rates of icu admittance and mortality in patients with sepsis due to any cause. compliance with ethics regulations: yes. abderrahim achouri, hadil mhadhbi, khedija zaouche, hamida maghraoui, radhia boubaker, kamel majed university hospital center rabta of tunis, tunis, tunisia correspondence: abderrahim achouri (achouryabderrahim@gmail. com) ann. intensive care , (suppl ):p- rationale: sepsis is a major cause of mortality. in other hand, preexistent chronic diseases seem to worsen outcomes among critically ill patients. the acknowledgement of this fact may motivate studies in this type of situations in order to improve survival in sepsis. on that purpose, our study tried to check the impact of chronic pre-existent illnesses on outcomes in this type of emergency patients. patients and methods: we have included patients in whom the sepsis- definition was met throughout emergency department admission cases for infection. in this study, considered outcomes were in-hospital mortality, shock occurence and the use of mechanical ventilation. results: we collected patients admitted to ed for sepsis. mean age was years ± with bornes of and . men were % of the patients. cormorbidities were: insulin dependent diabetes mellitus in . % of patients, non insulin dependent diabetes mellitus in . %, chronic obstructive lung disease in . %, chronic renal failure in . % with % in chronic replacement therapy from total patients, coronary artery disease in . %, with stent in . % and . % with aortic coronary graft from total patients, arterial hypertension in %, chronic heart failure in . %, atrial fibrillation in . %,. death occurs in . % of total patients, septic shock in % and the use of mechanical ventilation in . %. we did not find any association between comorbidity and the use of mechanical ventilation, but association with in-hospital mortality was found in pre-existent coronary artery disease (p = . ) and in patients with coronary artery stent (p = . ). odds ratio (or) was respectively . ( % ic = [ . - . ]) and . ( % ic = [ . - . ] ). we found significant association between chronic heart failure and shock (p = . ) with or = . ( % ic = [ . - . ] ). discussion: the small size of our sample may enlimit the contibution of other comorbidities on outcomes in sepsis such chronic renal failure, especially with renal replacement therapy and diabetes mellitus. whereas, we can conclude that cardiac diseases have the most important impact on outcomes in sepsis. outcomes in sepsis can be affected by comorbidities, especially cardiac diseases. therefore, that needs large studies to check it. compliance with ethics regulations: yes. micafungin population pk analysis in critically ill patients receiving continuous veno-venous hemofiltration or continuous veno-venous hemodiafiltration nicolas garbez , litaty mbatchi , steven c. wallis , laurent muller , jeffrey lipman , jason a. roberts , jean-yves lefrant , claire roger chu nîmes, nîmes, france; university of queensland, brisbane, australia correspondence: nicolas garbez (nicolas.garbez@umontpellier.fr) ann. intensive care , (suppl ):p- rationale: to compare the population pharmacokinetics (pk) of micafungin in critically ill patients receiving continuous veno-venous hemofiltration (cvvh, ml/kg/h) to those receiving equidoses of hemodiafiltration (cvvhdf, ml/kg/h + ml/kg/h). critically ill patients in septic shock undergoing continuous renal replacement therapy (crrt) and receiving mg micafungin once daily were eligible for inclusion. total micafungin plasma concentrations were analyzed using pmetrics ® . probability of target attainment (pta) was calculated from monte carlo simulations using -hour area under curve/minimum inhibitory concentration (auc - /mic) cut-offs (c. parapsilosis), (all candida species) and (c. non parapsilosis). daily dosing regimens of , and mg were simulated for the first days of treatment. results: eight patients were included in the study. micafungin concentrations were best described by a two-compartmental pk model. no covariate, including crrt modality (cvvh and cvvhdf), was retained in the final model, confirmed by internal validation. the mean parameter estimates (standarddeviation) were . ( . ) l/h for clearance, . ( . ) l for the volume of the central compartment, . ( . ) /h and . ( . ) /h for rate constants. the standard mg daily dosing was unable to reach % of pta for all candida species except c. albicans on the second day of therapy (fig. ) . conclusion: there was no difference in micafungin pk between equidoses of cvvh and cvvhdf. a dose escalation to mg is suggested to achieve the pk/pd target of candida species with mics exceeding . mg/l in this population. these "off-label" dosing regimens should be further investigated in clinical trials knowing the favourable toxicity profile and the post-antifungal effect of micafungin in order to ensure efficacy and to prevent the emergence of resistance due to an inadequate initial antifungal dosing regimen. compliance with ethics regulations: yes. rationale: sepsis is an important cause of morbidity and mortality in hospitalized patients. recognizing and responding to patients who experience clinical deterioration remains challenging in daily practice. our purpose was to assess the ability of the quick sequential organ failure assessment (qsofa) score to identify, among patients reviewed by an intensivist, those at risk of adverse outcomes. patients and methods: retrospective cohort of patients with suspected infection reviewed by an intensivist in a university-affiliated hospital between january and june . outcomes of interest were hospital mortality and a combined criterion of hospital mortality or icu stay of days or more. results: during the study period, patients were reviewed by an intensivist, of whom ( . %) had suspected infection according to the sepsis- criteria. at the time of review, ( . %) patients with suspected infection were qsofa positive (≥ ) and ( . %) were qsofa negative ( - ). following the review, ( . %) patients were admitted to the icu, among whom ( . %) had a prolonged stay (≥ days). in-hospital mortality was . %, and . % of the patients met the combined criterion of in-hospital mortality or prolonged icu stay. qsofa positive patients required more frequently mechanical ventilation ( . % vs. . %, p = . ) and vasopressor support ( . % vs. . %, p < . ) than qsofa negative patients. moreover, qsofa positive patients had higher hospital mortality than qsofa negative patients ( . % vs. . %, p = . ). for the prediction of in-hospital mortality, a positive qsofa had a predictive positive value (ppv) of %, and a negative predictive value (npv) of %. for the prediction of in-hospital mortality or prolonged icu stay, a positive qsofa had a ppv of % and a npv of %. conclusion: hospitalized patients with suspected infection for whom a review by an intensivist was requested, are at high risk of hospital mortality. although the accuracy of qsofa for identifying patients at risk of adverse outcomes is limited, its integration in a multimodal risk assessment approach may help distinguish the subset of patients who will benefit from an escalation of care. compliance with ethicsregulations: yes. rationale: according to the sepsis- consensus, sepsis is identified as an increase of at least points in the sepsis-related organ failure assessment (sofa) score in patients who presented infection. the quick sofa or qsofa is considered as a predictive tool of sepsis and mortality when it is equal to points or more. systemic inflammatory response syndrome (sirs) criteria are of limited utility because of their low sensitivity. hyperlactatemia, as known is a determinant of tissue hypoperfusion. our objective was to evaluate the prognostic value of sofa > , sirs > , qsofa > and lactate level > mmol/l in infected patients. nine-month prospective cohort study. patients aged years or older who had a proven or suspected infection were included. sofa score, sris criteria, sofa q and lactate levels were determined within the first h of infection. the primary endpoint was hospital mortality at days. the predictive power of the studied parameters was determined using using the area under the receiver operating characteristic curve (auroc). results: a cohort of cases was studied with mean age at . years. bacterial pneumonia was the most common infection site ( %). in the first h of onset of infection the medians [iqr - ] of the sofa, sris, and sofa scores and lactate levels were respectively [ ] [ ] [ ] [ ] [ ] [ ] [ ] , [ ] [ ] , [ - ] and . [ . - . ] . the progression to severe septic status was observed in patients ( %) and norepinephrine was introduced in cases. median length of stay was days [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] and mortality was %. overall, the accuracy in predicting mortality of the studied parameters was poor. an increase of sofa score by at least points had greater accuracy with auroc = . [ . - . ], sensitivity = % and specificity = %. conclusion: in infected patients, the sofa score had greater prognostic accuracy than the sirs criteria, the qsofa score or the lactate level. these results suggest that sirs, qsofa, and high lactate level may be useful in screening for sepsis, but this utility is limited in predicting mortality. compliance with ethics regulations: yes. rationale: quick sequential organ failure assessement (qsofa) has been validated for patients with presumed sepsis and others in general emergency department (ed) population. however, it has not been validated in specific subgroups of patients with a high mortality. the aim of this study is to evaluate the ability of qscore to predict prognosis in patients with decompensated liver cirrhosis. patients and methods: this is a retrospective study, conducted over a period of years from january to december . consecutive patients with decompensated cirrhosis, admitted in our department are included. data of all patients were collected and the qsofa score was calculated at admission. the main study endpoints were length of stay, complications and in-hospital mortality. results: a total of patients diagnosed with decompensated cirrhosis were enrolled. mean of age was years ( - ). sex ratio was . . hcv ( %) was the main etiology of cirrhosis. the reasons of hospitalization were: oedema with ascitic syndrome in % of cases, digestive haemorrhage ( % of cases), fevers ( % of cases), and hepatic encephalopathy was present in % of cases. the mean duration of stay was days ± . in-hospital mortality rate was % and mean score qsofa was . .the qsofa score was significantly correlated with length of stay (p = . ) and complications(p = . ) but not with in-hospital mortality (p = . ). conclusion: the qsofa score was not useful for predicting in hospital mortality in patients with decompensated liver cirrhosis but it was significantly correlated to the length of stay and complications. compliance with ethics regulations: yes. angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study clara vigneron , aldéric lécluse , thomas ronzière , sonia alamowitch , olivier fain , nicolas javaud médecine interne, centre de référence associé sur les angioedèmes à kinines (créak), hôpital saint-antoine, aphp, paris, france; neurologie, chu angers, angers, france; neurologie, chu pontchaillou, rennes, france; neurologie, hôpital saint-antoine, aphp, paris, france; urgences, centre de référence associé sur les angioedèmes à kinines (créak), hôpital louis mourier, aphp, colombes, france correspondence: clara vigneron (claravigneron@hotmail.fr) ann. intensive care , (suppl ):p- rationale: bradykinin-mediated angioedema is a complication associated with thrombolysis for acute ischemic stroke. risk factors are unknow and management is discussed. the aim of this study was to clarify risk factors associated with bradykinin-mediated angioedema after thrombolysis for acute ischemic stroke. patients and methods: in a case-control study conducted at a french reference center for bradykinin angioedema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angioedema, were compared to controls treated with thrombolysis treatment without angioedema. two matched control subjects were analyzed for each case. results: thrombolysis-related angioedema were matched to control subjects. the sites of attacks following thrombolysis for ischemic stroke mainly included tongue ( / , %) and lips ( / , %). the upper airways were involved in ( %) cases. three patients required mechanical ventilation. patients with bradykinin-mediated angioedema were more frequently women ( ( %) vs. ( %); p = . ), had higher frequency of prior ischemic stroke ( ( %) vs ( %); p = . ), hypertension ( ( %) vs. ( %); p = . ), were more frequently treated with angiotensinconverting enzyme inhibitor ( ( %) vs. ( %); p < . ) and were more frequently hospitalized in intensive care unit ( ( %) vs. ( %); p = . ). in multivariate analysis, factors associated with thrombolysisrelated angioedema were female sex (odds ratio [or], . ; % confident interval [ci], . - . ; p = . ) and treatment with angiotensin-converting enzyme inhibitors ([or], . ; % [ci], . - . ; p < . ). discussion: because of theretrospective case-control design and the lack of the total number of thrombolysis for ischemic stroke, the incidence of this complication could not be evaluated in our study. previous studies reported an incidence of . to . % of angioedema in patients treated with a thrombolytic therapy for acute ischemic stroke. our case-control study permits for the first time to analyse more cases to evaluate associated risk factors of this rare complication. conclusion: this case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykininangioedema associated with thrombolysis for ischemic stroke. compliance with ethics regulations: yes. rationale: patients with inflammatory bowel disease (ibd), frequently treated by immunosuppressive drugs, are more susceptible to be admitted to the intensive care unit (icu). however, outcome and predictive factors of mortality are little known. therefore, we aimed to assess the outcome and prognostic factors for critically ill ibd patients. patients and methods: we retrospectively studied data of consecutive ibd (i.e. crohn's disease and ulcerative colitis) patients admitted in icus between and . in-icu and one-year mortalities were estimated and predictive factors of in-icu mortality were identified by univariate and multivariate analysis. results: seventy-six patients (male: %, median age: . [ . - . ] years, charlson index: [ . - . ]) entered the study. ibd type was largely represented by crohn's disease ( . %) and its localization was mostly extensive: l ( . % of crohn's disease) or e ( % of ulcerative colitis) according to the montreal classification. twenty-seven patients ( . %) were treated with corticosteroids and ( %) with immunosuppressive therapy (azathioprine: . % and anti-tnfα: %). reasons for admission were shock/sepsis ( . %) and acute respiratory failure ( . %). icu diagnoses were infection ( %), ibd flare-up ( . %) or both ( . %), and pulmonary embolism ( . %). at admission, sofa score was [ . - . ] and . fifty-three patients ( . %) required mechanical ventilation, ( . %) vasoactive drugs, and ( . %) renal replacement therapy. twenty-three patients underwent emergency surgery ( . %) and six urgent endoscopic treatment ( . %). in-icu and one-year mortality rate were . % and . %, respectively. prognostic factors of in-icu mortality were sofa score (hr . , % ci [ . - . ], p < . ) and azathioprine treatment before icu admission (hr . , % ci [ . - . ], p < . ) (fig. ) . previous immunosuppressive treatment with anti-tnf did not alter the prognosis and even the type of ibd. conclusion: our study showed that more than % of ibd critically ill patients were discharged alive from the icu and a majority of them survived after one-year ( . %). we also found that sofa score and previous azathioprine immunosuppressive treatment worsened icu outcome. higher severity of the acute event affected short-term prognosis and should be taken into account for best icu triage and management. intensivists should pay particular attention to patients treated by azathioprine. compliance with ethics regulations: yes. fig. outcome of ibd patients admitted to the icu according to precious treatment with azathioprine status all aps patients with any new thrombotic manifestation(s) admitted to icus. results: one hundred and thirty-four patients (male/female ratio: . ; mean age at admission: . ± . years), who experienced caps episodes, required icu admission. the numbers of definite, probable or no-caps episodes (fig. ) , respectively, were: ( . %), ( . %) and ( . %). no histopathological proof of microvascular thrombosis was the most frequent reason for not being classified as definite caps. overall, / ( . %) episodes were fatal, with comparable rates for definite/probable caps and no caps ( % vs. . % respectively, p = . ). the kaplan-meier curve of estimated probability of survival showed no between-group survival difference (log-rank test p = . ). discussion: our results suggest that the caps criteria do not sufficiently encompass all the parameters responsible for thrombotic aps patients' disease severity in the icu. the absence of items referring to organ dysfunction/failure in the caps criteria probably limited their ability to predict mortality. albeit useful for the retrospective classification and comparison of patients, the caps criteria may be too stringent and not yet ready-to-use for the management of icu patients. for physicians outside expert aps centres, the absence of caps criteria could be misleading and lead to rejection of the diagnosis for near-caps patients, thereby preventing them from receiving the appropriate aggressive treatment they indeed require. we think that, when confronted with a critically-ill thrombotic aps patient, caps criteria should be interpreted with caution and should not be the only elements taken into account to decide the intensity of the therapeutic management. rationale: % of resuscitation patients develop anemia during their stay, it can worsen the prognosis, prolong the length of stay and lead to transfusions that can be the cause of complications. the objective of our work is to specify the incidence of anemia in our unit, its etiologies and its therapeutic management. patients and methods: we conducted a descriptive and analytical retrospective study within the surgical emergency resuscitation department of ibn rochd university hospital of casablanca, over a period of years from to . we included all anemic patients. statistical analysis was performed with spss statistics . p < . was considered significant. results: we included patients with an estimated incidence of %, the average age was years, the sex ratio h / f was . . % of admissions were for traumatic pathology and % postoperative digestive surgery. % had hypotension at admission and the mean temperature was . % .the onset of anemia and its depth were related to length of stay with . % of patients who were anemic beyond the th day of hospitalization with a hemoglobin level that became < . g / dl beyond the th day. % of the patients had a normochromic normocytic anemia becoming microcytic with the lengthening of the duration of stay. ferritinemia dosed in % of patients and was normal. % of our patients had exclusive parenteral nutrition while % had an enteral / parenteral combination. % were transfused in red blood cells (rbc) and % of patients were transfused more than once. % received between and rbc units. in patients who received transfusion episodes costing euros, the transfusion was inappropriate. the total cost of the transfusion was estimated at around , euros. % were supplemented with oral iron with an increase in hemoglobin in % of them. % of the patients came out of the intensive care unit with a hemoglobin level < g/dl/l. the mortality rate of our patients was % with as predictive factors in multivariate analysis, hyperthermia, coagulopathy, the transfusion appears as a factor of good prognosis. the prevention of blood spoliation and the fight against inflammation and nosocomial infection remain the pillars of the management of anemia in intensive care but in view of our results and the protective role of transfusion it would be interesting to see again the transfusion thresholds in our context. compliance with ethics regulations: yes. (fig. ). discussion: we described a series of patients with severe acute viral myopericarditises associated with anti-rnapol autoantibodies, an association that has never been reported previously. the fortuitous association of these autoantibodies with acute myopericarditis is highly unlikely. acute myocarditis is a very rare disease with a reported incidence of / , inhabitants. anti-rnapol -antibody detection is also very rare: . % positive tests (including the patients in this series) out of samples during a -year period in our immunology laboratory. this % proportion of patients with proven influenza-virus infections suggest that such severe infections could trigger anti-rnapol autoantibody production. however, influenza is a common disease and anti-rnapol autoantibodies are very rare. furthermore, no anti-rnapol autoantibodies were detected in the patients with severe influenza-related ards. last, anti-rnapol autoantibodies remained detectable several months after the viral infection had been cured. conclusion: this previously unknown association between severe acute viral myopericarditis and anti-rnapol autoantibodies is probably not fortuitous. anti-rnapol antibody detection in acute myopericarditis patients could imply individual susceptibility to severe viral infection. further studies are needed to investigate the pathophysiological mechanisms involved in this entity and potential specific therapeutic strategies. fig. relative frequencies of digestive manifestations in critically ill tma patients rationale: arrhythmia-induced cardiomyopathy has been recognized for several decades, but most severe forms, i.e. cardiogenic shock and refractory cardiogenic shock requiring mechanical circulatory support, were rarely described in adults. in this retrospective study, we described patients admitted in our tertiary care center for non-ischemic acute cardiac dysfunction (or worsening of previously known cardiac dysfunction) and recent onset supraventricular arrhythmia who developed cardiogenic shock requiring veno-arterial ecmo (va-ecmo). results: in a years period, patients had va-ecmo for acute non ischemic cardiac dysfunction and recent onset supraventricular arrhythmia (table ). fourteen ( %) patients had known nonischemic cardiomyopathy and ( %) known paroxystic atrial fibrillation. cardiogenic shock was the first manifestation of the disease in patients. atrial fibrillation was the main cause of arrythmia ( % of cases). at ecmo implantation, sofa score was [ - ], inotropic score , lvef % [ - ] and lactate level was [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] mmol/l. twelve patients had sustained successful reduction after amiodarone and/or electric shock, all were weaned from ecmo and survived without transplantation nor long term assist device. among the patients with failure of reduction, underwent an atrio-ventricular ablation while on ecmo and had atrial tachycardia ablation; all were weaned from ecmo and survived. among the remaining patients without reduction and without ablation procedure, only the patients who were bridged to heart transplantation or left ventricular assist device survived. in univariate analysis, factors associated with unfavorable outcome were previously known heart disease, heart rate, renal replacement therapy, nt-probnp level, failure of rhythm reduction after amiodarone load and/or electric shock. among the patients who recovered and survived ( with successful reduction and with successful ablation), lvef increased from [ - ]% before ecmo implantation to [ - ]% at long term follow-up. discussion: this is the largest cohort of arrhythmia induced cardiomyopathies on va-ecmo and the first description of atrio-ventricular node ablation with favorable outcome in this setting. conclusion: arrhythmia induced cardiomyopathy is probably underrecognized and should be considered in any patient with nonischemic acute cardiac dysfunction and recent onset supraventricular arrhythmia. recovery is possible in the most severely ill patients on va-ecmo, even with severe left ventricular dilation. aggressive rate control by av-node ablation may be warranted in case of failure of reduction, and may allow recovery and favorable outcome. compliance with ethics regulations: yes. rationale: diagnosis of sepsis is a major challenge in intensive care units and is associated with a high morbidity and mortality. sepsis identification is even more difficult in patients with extracorporeal membrane oxygenation (ecmo) because of many confounding factors. the primary objective was to study the ability of c-reactive protein (crp) and procalcitonin (pct) values measured at ecmo support initiation (day ) to predict the occurrence of early sepsis in patients undergoing venoarterial ecmo (va-ecmo) or venovenous ecmo (vv-ecmo). the secondary objectives were to study the association between these biomarkers and mortality rate during ecmo support and in-hospital mortality rate. furthermore, we investigated the relationship between early sepsis and mortality. patients and methods: we performed a retrospective, monocentric study in the cardiovascular intensive care unit of the university hospitals of lille, france. between november , and december , , we included patients over years old, who underwent an ecmo support for a medical or surgical indication, and for whom biomarkers (crp and pct) levels were available for at least the first days of admission. biomarkers and blood cultures were daily assessed for the first ecmo support days. early sepsis was defined by sepsis diagnosis in the first days after circulatory assistance initiation. in-hospital mortality rate was censored at days. after univariate analysis, a cox multivariate regression model was used to assess if the association between biomarkers levels and early sepsis or mortality rate was independent. a kaplan-meier survival plot was used to describe the association between early sepsis and mortality. results: among patients included, underwent va-ecmo and underwent vv-ecmo. an early sepsis diagnosis was made in . % of va-ecmo patients and in % of vv-ecmo patients. pct and crp levels on day were significantly associated with early sepsis diagnosis (fig. rationale: fluids are one of the most prescribed drug in intensive care, particularly among patient with circulatory failure. yet, very little is known about their pharmacodynamic properties and this topic has been left largely unexplored. several factors may impact the haemodynamic efficacy of fluids among which the infusion rate. the aim of this study was to investigate the influence of the rate of fluid administration on the fluid pharmacodynamics, in particular by studying mean systemic pressure (pms). we conducted a prospective observational study in patients with septic shock to compare two volume expansion strategies. a fluid bolus, ml of normal saline were administered and several haemodynamic variables were recorded continuously: cardiac output (co), arterial pressure (ap), mean systemic pressure (pms, estimated from ci, pvc and map). infusion rate was left at the discretion of the attending physician. a "slow" and a "fast" groups were determined based on the median of the infusion duration. fluids effect was measured by the area under the curve (auc), maximal effect (emax) and time to maximal effect (tmax) for each haemodynamic variable. the effects of fluid on psm disappeared in one hour on average. compared to patients of the "slow" group, those of the "fast" group had a shorter tmax and a higher emax for pms (p = . and . respectively). the auc for pms was identical between group, while in case of similar effect of infusion rates, it should be larger in the "slow" group. regarding co, tmax was also shorter in the "fast" than in the "slow" group (p = . ). the decreasing slope from maximal effect was comparable between groups, for pms as for co. the effect of a ml fluid bolus with normal saline in septic shock patients vanished within one hour. a faster infusion rate increased the maximal and total effect of the fluid bolus and shortened the delay to reach the maximal effect. rationale: significant hypotension following spinal anesthesia is a common issue in everyday clinical practice. toavoid this potentially harming situation, an empirical fluid administration is usually performed before the procedure. inferior vena cava (ivc) ultrasound has been demonstrated effective in guiding fluid therapy in critical care patients. the purpose of this study was to evaluate the ivc ultrasound guided volemic status optimization in order to decrease post-spinal hypotension rate. patients and methods: in this prospective, controlled, randomised study, consecutive patients were recruited and patients were randomly assigned to a control group, consisting of pre-anesthesia empirical fluid administration (itt), an ivc ultrasound group in which fluid management was based on an ivc ultrasound evaluation, and a passive leg raising test (plrt) group in which volume optimization was performed following the above mentioned test. primary outcome was the hypotension rate reduction after spinal anaesthesia following fluid optimization therapy between the groups. secondary outcomes were the total fluid amount administered, the total vasoactive drug amount used and the time needed to realize the whole anaesthetic procedure in all three groups. results: % reduction in hypotension rate ( % ci - %, p = . ) was observed between the echocardiography group and the control group, and there was a reduction of hypotension rate by % (ci % - %, p = . ) between the echocardiography group and the plrt group. the total fluid amount administered was significantly greater in the ultrasound group than in the control group ( ml; sd ml, versus ml; sd ml, p = . ). the total amine consumption was % in control group, % in ivc group and % in plrt group. an increased of total study time was observed for the echocardiography group min (sd min) in comparison with the control group min (sd min) and ptlr group min (sd min), (p < . ). the study showed a faint but positive trend toward the use of ivc-ultrasound to identify patients in spontaneous breathing needing fluid optimization before spinal anesthesia compliance with ethics regulations: yes. rationale: we performed a systematic review and a meta-analysis of studies investigating the ability of the end-expiratory occlusion (eexpo) test to predict preload responsiveness, through the changes in cardiac output (co) or its surrogates, in adult patients. this meta-analysis was prospectively registered on prospero (crd- ). we screened pubmed, embase and cochrane database to identify all original articles published between and evaluating the ability of the eexpo test to predict a significant increase in co or surrogate, compared to the one induced by a subsequent volume expansion or by passive leg raising (plr). the meta-analysis determined the pooled area under the receiver operating characteristics curve (auroc) of eexpo testinduced changes in co to detect preload responsiveness, as well as pooled sensitivity and specificity and the best diagnostic threshold. subgroup analysis and sensitivity analysis were planned to investigate potential sources of heterogeneity. results: thirteen studies ( patients) were identified and included in the analysis. nine studies were performed in the intensive care unit and four in the operating room. preload responsiveness was defined according to co changes induced by fluid administration in studies (fluid-induced increase in co ≥ % or ≥ %) and according to co changes induced by plr in one study. the duration of the respiratory hold ranged between and s. for the eexpo test-induced changes in co, the pooled sensitivity and specificity were [ - ]% and [ - ]%, respectively, while the pooled auroc curve was . ± . (fig. ) . the corresponding best diagnostic threshold was . ± . %. when changes in co were monitored through pulse contour analysis compared to other methods the accuracy of the test was significantly higher ( ( ). continuing (decrease to % of peak level) or modification (decrease < %) of antibiotic therapy was guided by a serum pct assay from the third day of treatmentand every h until antibiotic was stopped. this last was stopped when pct levels had decreased of % from the initial value. results: a total of patients had been diagnosed as sepsis (n = , %) and septic shoc (n = , %). mean age was years ± . an average ubs and absi score of % and . the average length of stay in icu was days. patients were assigned into two groups: group a (favorable evolution, n = ); group b (unfavorable evolution, n = ). the therapeutic attitude according to the kinetics of the pct are presented in the table . we found a significant difference between patients with unfavorable evolution compared to those with a favorable evolution (in whom we stopped antibiotics) (p < . ), in terms of hemodynamic state, pct concentration and renal clearance. pctguided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in our patients. the average duration of antibiotic was . ± days. conclusion: pct measurement may help with the decision to initiate antibiotic therapy in low risk acuity of infection and allows more judicious antibiotic use by reducing antibiotic exposure. compliance with ethics regulations: not applicable. rationale: reducing the risk of severe hypoxemia during endotracheal-intubation (eti) is a major concern in intensive care unit but little attention was paid to co variations during this period. we conducted a prospective observational study to describe transcutaneous co (ptcco ) throughout intubation in patients who received preoxygenation with standardoxygen therapy (sot), non-invasive ventilation (niv), or high flow nasal cannula oxygen therapy (hfncot). patients and methods: patients over years undergoing eti in icu were continuously monitored for ptcco during intubation and the following h under mechanical ventilation (mv). haemodynamics and respiratory parameters were also recorded as well as arterial partial pressure of co (paco ) to evaluate reliability of the transcutaneous measure. results: two hundred and two patients were included in the study. we found a strong correlation between ptcco recorded at preoxygenation and the last paco available before intubation (r = . , p < . ). in % of patients ptcco values recorded at initiation of mv were out of - mmhg ranges. ptcco recorded at eti, at initiation of mv, min and h of mv were significantly higher than ptcco during preoxygenation (p < . by anova). variations of ptcco were significantly different according to the preoxygenation method (p < . for interaction in anova). lastly, a decrease in ptcco higher than mmhg within half an hour after the beginning of mv was independently associated with postintubation hypotension (pih) (odds ratio = . , % confident interval . - . , p = . ). conclusion: ptcco is a valuable tool to record paco variation in patients requiring invasive mechanical ventilation and could be useful to prevent pih. compliance with ethics regulations: yes. rationale: intubation in intensive care unit (icu) is a critical procedure which leads to serious adverse event in to % of cases. several recent trials were conducted to help physicians to choose medications, devices and modality of intubation. especially, videolaryngoscope (vl) led to several publications in the last few years, with increasing tools marketed and spread use (difficult airway management, routineintubation). we designed an online survey to take a picture of intubation process and devices availability in france. toolbox. it was positioned as a first line laryngoscope for every intubation in critically ill patients to reinforce the vl skill training. present study was performed using prospectively collected data from a continuous quality improvement database about airway management in a -beds french teaching hospital medical icu. all consecutive intubation procedure performed with vl from september to june were included. "first attempt success" group and "first attempt failure" group were compared by univariate and multivariate analysis in order to analyze the first attempt intubation success rate according to the level of operators' expertise, identify factors associated with first pass intubation failure and describe the intubation related complications. results: we enrolled consecutive endotracheal intubations. overall first attempt success rate was ( %). comorbidities, junior operator, the presence of cardiac arrest and coma were associated with a lower first attempt success rate. the first attempt success rate was less than % in novice operators ( - previous experiences with vl, independently of airway expertise with direct laryngoscopies) and % in expert operators (greater than previous experiences with vl) (fig. rationale: tracheostomy in intensive care unit (icu) has many advantages. but only patient comfort and shorter icu and hospital stay were demonstrated. the timing of this procedure is still debated. the aim of this study was to determine the impact of early tracheostomy on prognosis. we performed a retrospective study in a medical icu ( beds unit) from january to november . the technique of tracheostomy was exclusively surgical in the operating room made by the surgeon. the primary endpoint was mortality in icu. the secondary outcomes were post-tracheostomy incidence of ventilator acquired pneumonia, duration of mechanical ventilation and length of stay in icu. these criteria were assessed in relation to timing of the tracheostomy defined as early when performed before day of mechanical ventilation. results: forty-two patients were enrolled during the study period. mean age of patients was ± years. median length of stay in icu was of days. mortality rate was of %. comparing the two groups, early vs late tracheostomy, no difference was found with respect to mortality ( % vs. %, p = . ), vap occurrence ( % vs. %, p = . ), post-tracheostomy duration of mechanical ventilation ( ± d vs. ± d, p = . ), or length of stay in icu ( ± d vs. ± d, p = . ). in multivariate analysis, the only factor independently related to mortality was the sofa score patient on tracheostomy day with p = . and or = . (ci % [ . - . ] ). conclusion: tracheostomy in the intensive care unit remains a justified alternative despite the discordant data in the literature. in our study, the delay of the procedure didn't interfere with the evolution. however, the patient severity as attested by sofa score at the day of tracheostomy, was the only independent prognostic factor. those results should be confirmed by other large prospective studies. compliance with ethics regulations: not applicable. sabah benhamza, mohamed lazraq, youssef miloudi, abdelhak bensaid, najib el harrar réanimation de l'hôpital du août, casablanca, morocco correspondence: sabah benhamza (benhamzasabah @gmail.com) ann. intensive care , (suppl ):p- rationale: many unknowns remain as to the place of tracheostomy in intensive care. reluctance to perform a tracheotomy is numerous, especially when pre-exists chronic respiratory failure, but some data suggest benefits. we report in this work our experience in tracheotomy in the intensive care unit of the august hospital, casablanca. patients and methods: this is a retrospective descreptive study over years (january to january ) including all patients that have been tracheostomized in the intensive care unit of the august hospital . results: during the study period, patients were tracheostomized with a prevalence of . % in years, the predominance was male (sex ratio . ). the average age was ± years old. the indication for tracheostomy was prolonged ventilation in % of cases, extubation failure in % of cases, and intubation failure in % of cases. tracheostomy was performed on average on the th day of intubation. all patients were tracheostomized in the operating room by ent surgeons. the main complications attributable to tracheotomy were hemorrhage of the tracheostomy orifice in patients ( %) immediately resumed, cases of subcutaneous emphysema ( %), case of pneumothorax ( %), cases of orifice infection ( %). no patient died of a tracheostomy related cause. the tracheotomy in intensive care is still a subject of debate especially concerning the time of its realization. however it seems to reduce the duration of mechanical ventilation, facilitates the care and also the ventilatory weaning. compliance with ethics regulations: yes. rationale: hfnco is a frequently used device providing heated and humidified high flow oxygen with several advantages: decreased work of breathing, decreased dead space, increased end expiratory lung volume (eelv), more stable fio . the increase in eelv is relying of the positive expiratory effect generated by the device. the level of generated pep seems however to largely depend on whether the mouth is open or not. this study was aimed to assess the impact of mouth opening on eelv increase induced by hfnco using electric impedance tomography. patients and methods: the following hfnco trial was proposed to healthy subjects who used hfnco on a regular basis for patients care. oxygen flow was set successively during min periods at , and l/min (optiflowtm; fisher & paykel healthcare, auckland, nz). these three conditions were tested in semi recumbent and supine position chosen at random. measurement started in supine position with no flow (baseline) and each period was separated from the following by a wash out period on min during which the subject could breath normally with no supplemental oxygen. electric impedance tomography (pulmovista ® , dräger medical gmbh, lündbeck, germany) was performed applying a electrodes belt placed between the th and th intercostal space, including a reference electrode located on the abdomen. as no spirometer was used, the data of eelv computed on the eit device were expressed as percentage of variation of the value measured in supine or semi recumbent position with no flow. demographic data were expressed as median and extreme values. comparisons were performed using u mann whitney test. [ . - . ] accepted to participate to the study. when subjects received hfnco with open mouth (whatever position) no modification of eelv was observed (table ) . conversely, a significant increase in eelv was noted with closed mouth, whatever position. in the semi recumbent position the increase in eelv was even more important with l/min. conclusion: electrical impedance tomography illustrates the impact of mouth closure on eelv increase among healthy subjects receiving hfnco. compliance with ethics regulations: yes. rationale: in stable copd patients, nasal high flow oxygen (nhf) use can be associated with reduction in respiratory rate (rr) and minute ventilation (mv). in thesepatients, paco remains stable or decreases under nhf. this suggests a possible dead space reduction related to a washout effect of nhf. the aim of this study was to assess the physiological effects of nhf in hypercapnic patients with acute copd exacerbation. patients and methods: crossover study in hypercapnic patients suffering from acute copd exacerbation and treated with intermittent non-invasive ventilation (niv). nhf l/min or standard oxygenotherapy (stand o ) were randomly administered during h between niv treatments. rr, tidal volumes (vt), mv and corrected mv (cormv = mv x paco / ) variations were recorded during the last min of each study period using a respiratory inductive plethysmography vest. blood gas analysis was performed at the end of each oxygen administration period. visual analogic dyspnea score (vas) quoted from to was assessed by the patient after and min. results given as median [iqr] . wilcoxon tests were used to compare data between stand o and nhf. results: twelve patients were included and data could be recorded in ( (fig. ). dyspnea scores were not different between the modalities. conclusion: in case of acute copd exacerbation, using nhf between niv treatments was associated with paco and rr decrease. mv concomitantly decreased suggesting a deadspace volume reduction related to a washout effect of nhf. corrected mv decreased in all the patients except one. these results suggest that nhf could be used to deliver oxygen between niv treatments to copd patients suffering from acute exacerbation and could contribute reducing paco . compliance with ethics regulations: yes. rationale: the role of atypical micro-organisms in acute exacerbation of chronic obstructive pulmonary disease (copd) that require mechanical ventilation is poorly none. the aim of this study was to determine the role of atypical pathogens in severe acute exacerbation of copd. patients and methods: in this prospective study we included all patients admitted for acute exacerbation of copd requiring mechanical ventilation. atypical pathogens (chlamydophila pneumoniae and mycoplasma pneumoniae) were searched by serological diagnosis and by culture of sputum samples. in this study we included patients aged ± years. sixty-eight percent of sputum culture were considered significant. six cultures were positive with different microorganisms. neither chlamydophila pneumoniae nor mycoplasma pneumoniae were found. the prevalence of chlamydophila pneumoniae was . % (positive igg serum). the demographic characteristics was similar between patients with and without positive culture. the rate of noninvasive ventilation (niv) failure was % in positive serology group versus % in negative serology group (p = . ). the mortality was similar in both groups. in multivariate logistic regression analysis only positive serology (or = . ; % ic [ . - . ], p = . ) was an independent factor of niv failure. conclusion: a positive serology of chlamydophila pneumoniae was a predictive factor of niv failure without an impact on the morbidity and mortality of copd patient treated with mechanical ventilation. compliance with ethics regulations: yes. rationale: emergency departments (ed) receive a growing up number of patients with acute exacerbation of chronic obstructive pulmonary disease (copd) .non-invasive ventilation (niv) could be a good alternative to achieve a respiratory support, avoiding as much as possible the complications of invasive ventilation. the study aimed to assess the clinical outcomes of using niv in acute exacerbation of copd at ed and to identify whether clinical variables present at admission are predictive of niv failure. we conducted a prospective study conducted at the ed over a period of one year. data of all patients admitted for acute exacerbation of copd for all causes and requiring non-invasive ventilation were collected. niv failure was defined as need for endotracheal intubation or death. results: during the study period, a total of patients with a mean age of years (± ) were included. acute exacerbation of copd was due to bronchitis in %, to pneumonia in % of cases. % of patients had no apparent etiology of acute exacerbation of copd. bilevel positive airway pressure was performed on all patients, during a mean period of h (± ). clinical niv success was observed in patients ( %). the predictors of niv failure were advanced age, tachycardia, and hypercapnia. conclusion: the efficiency of niv in the management of acute exacerbations of copd at ed is well documented. this is further supported by our study which showed a clinical success in % of patients with acute exacerbation of copd. compliance with ethics regulations: yes. rationale: non invasive ventilation (niv) is often performed in elderly patients with acute respiratory failure (arf) at emergency department (ed). this technique may be subject to many difficulties, due to the presence of frequent co-morbidities. the aim of this study was to identify the predictive factors of niv failure in elderly patients with arf at ed. patients and methods: this was a retrospective study conducted at ed on year and months including patients aged more than years and who required the use of niv for an arf. all data were collected and analyzed using the spss software. patients were divided into two groups: niv failure and niv success. niv failure was defined by inhospital mortality, requirement of intubation or hospitalization at intensive care unit. results: during the study period, a total of elderly patients that required niv for arf were included. median age was years (min = , max = ) and sex ratio was . . the median charlson index was (min = , max = ). the etiological diagnoses of arf were acute decompensation of chronic obstructive pulmonary disease ( %), acute heart failure ( %), pneumonia ( %) and pulmonary embolism ( %). the arf was hypercapnic in % of cases and nonhypercapnic in %. niv failure concerned %. predictive factors of niv failure were clinical signs of right heart dysfunction (p < . ), c reactive protein (p = . ), initial ph (p = . ) and kidney dysfunction (p < . ). conclusion: in our study, niv failure in elderly patients with arf at ed was influenced by clinical signs of right heart dysfunction, c reactive protein, initial ph and kidney dysfunction. these clinical and biological factors could be useful to identify the most critical elderly patients and to better guide therapeutic decisions. compliance with ethics regulations: yes. rationale: the interest of ecco r in the management of very severe acute asthma exacerbations is still unclear. since it could help to control respiratory acidosis and /or to limit dynamic hyperinflation, its clinical benefits are uncertain, even in mechanically ventilated patients. the rexecor observatory is a prospective ecco r cohort in the great paris area. tencases of severe asthma treated by ecco r were retrospectively reviewed. mainly, arterial blood gases (abg), duration of ecco r and imv were collected and in-icu mortality were assessed. data are reported as median (iqr). results: ten patients ( men, age: (ic: - ) years, bmi: . (ic: . - . ) kg/m , fev- : . (ic: . - . ) l, ( (ic: - ) %), saps : . (ic: . - . ) points) were included. one patient suffered from cardiac arrest before admission and one had pneumothorax at icu admission. nine patients were under imv (started on the day of admission for ). before ecco r, patients received systemic corticosteroids, paralyzing agents, epinephrine and salbutamol. two patients suffered from pneumonia. ecco r was started (ic: - . ) days after intubation. venous vascular access was achieved via the right internal jugular route in patients and via the femoral route in . the hemolung device was used in patients, the ila activve in and the prismalung in . abg before and after day of ecco r are reported in table . duration of ecco r was (ic: . - ) days and patients were weaned from imv under ecco r. for the remaining patients, duration of imv after ecco r was (ic: - . ) days. icu stay was . (ic: - . ) days. the only one niv patient was not intubated. ecco r as stopped in patients because of complications (one hemolysis, one internal bleeding and one membrane clotting). one patient died in icu after limitation of life-sustaining therapy decision. we report a preferential use of ecco r in imv patients, contrasting with a marginal use in only one niv patient to prevent intubation. the mortality rate was low, in line with previous case series of severe acute asthma with ecmo or ecco r support. more studies are needed ( ) to better delineate the pathophysiological benefits of ecco r in asthma patients and ( ) to confirm strong clinical benefits. compliance with ethics regulations: not applicable. rationale: acute exacerbations of chronic obstructive pulmonary disease (aecopd) are the most important events characterizing respiratory illness progression. their management often needs noninvasive or invasive ventilation (iv). data of literature confirm that the mortality of aecopd requiring iv is high but are discordant about prognostic factors. the aim of our study was to describe the epidemiologic and clinical features of patients admitted for aecopd requiring iv, the treatment and the evolution in intensive care unit in order to deduce the independent factors of mortality. patients and methods: a -year retrospective analytic observational single-center study including patients hospitalized for aecopd requiring iv. results: fifty-eight patients were enrolled. mean age was ± years with sex-ratio of . . eighty one percent were smokers and % were classified gold stage . history of intensive care hospitalization and prior iv were found in % and % of all cases respectively. mean apache ii score was ± . the predominant precipitating factor for aecopd was respiratory tract infection ( % of all cases). twenty two percent of all patients presented septic shock. iv was initiated on admission in % of all cases and after noninvasive ventilation failure in % of all cases. forty-eight per cent of all patients developed septic shock as evolutionary complication. mortality rate was %. in univariate analysis: male gender (p = . ), duration of respiratory disease progression (p = . ), annual exacerbations frequency (p < − ), gold stage (p = . ), prior iv (p < − ), duration of symptoms before hospitalization (p = . ), apache ii score (p = . ), ph (p = . ), shock on admission (p = . ) and septic shock as evolutionary complication (p = . ) were predictors of mortality in our study. besides; shock on admission (p = . ) and as evolutionary complication (p = . ) were the two independent prognostic factors in multivariate analysis. conclusion: vital and functional prognosis of aecopd requiring iv depends on the severity of the underlying respiratory illness, the severity of the exacerbation and the quality of an early management. this emphasizes the importance of controlling modifiable risk factors including smoking cessation, basic treatment improvement and early appropriate treatment of these exacerbations. compliance with ethics regulations: yes. medical background, biological parameters, death-rate and outcome of patients have been compared. results: in total, patients have been included in the "hlh" population. death-rate in intensive care unit was % in the "hlh" group compared to % in the "not hlh" group (p = . ). we used more extrarenal cleansing in the "hlh" group ( % vs. %, p < . ), the duration of assisted ventilation was longer ( . days vs. . days, p < . ), as well as the duration of extrarenal cleansing ( . days vs. . days, p < . ) and those of amines ( . days vs. . days, p = . ). the average time of hospitalization was significantly longer in the "hlh" group ( . days vs. . days, p < . ). the secondary hlh to sepsis in intensive care unit, not well known and understudied, seems to have a different profile and a more serious outcome but no change in death-ratehas been found considering the pairing with the sofa. further studies are needed to plan a better therapeutic strategy within this population. compliance with ethics regulations: not applicable. serum and peritoneal exudate concentrations after high doses of ß-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study lisa leon, philippe guerci, elise pape, nathalie thilly, amandine luc, adeline germain, anne-lise butin-druoton, marie-reine losser, julien birckener, julien scala bertola, emmanuel novy chru nancy, vandoeuvre les nancy, france correspondence: lisa leon (lisaleon @gmail.com) ann. intensive care , (suppl ):p- rationale: critically ill patients with severe intra-abdominal infections (iais) requiring urgent surgery may undergo several pharmacokinetic alterations that can lead to ß-lactam under dosage. the aim of this study is to measure serum and peritoneal exudate concentrations of ß-lactams after high doses and optimal administration schemes. patients and methods: this observational prospective study included critically ill patients with suspicion of iai who required surgery and a ß-lactam antibiotic as empirical therapy. serum and peritoneal exudate concentrations were measured during surgery and after a h steady-state period. the pharmacokinetic/pharmacodynamic (pk/ pd) target was to obtain ß-lactam concentrations of % ƒt> x mic (minimum inhibitory concentration) based on a worst-case scenario (highest ecoff value) before bacterial documentation (a priori) and redefined on the mic of the isolated bacteria (a posteriori). results: forty-eight patients were included with a median [iqr] age of [ - ] and a saps ii score of . septic shock occurred in % of cases. the main diagnosis was secondary nosocomial peritonitis. piperacillin/tazobactam was the most administered ß-lactam antibiotic ( %). prior to bacterial documentation, patients ( . %) achieved the a priori pk/pd target. iai was documented in patients ( %). enterobacteriaceae were the most isolated bacteria. based on the mic (n = ) of isolated bacteria, % of the patients achieved the pk/pd target ( % ƒt> xmic). in the fig. we presented serum ß-lactams pk/pd target attainment and observed total concentrations of piperacillin-tazobactam at each timepoint in serum and peritoneal exudate. in critically ill patients with severe iais, high doses of ß-lactams ensured % ƒt> xmic in % of critically ill patients with severe iais within the first h. a personalized ß-lactam therapeutic scheme with a pk/pd target based on local ecology should be warranted. compliance with ethics regulations: yes. rationale: intensive care unit acquired bloodstream infections (icu-bsi) are frequent, and associated with high morbidity and mortality rates. the objective of our study was to describe the epidemiology and the prognosis of icu-bsi in our icu (cayenne general hospital). secondary objectives were to search for factors associated to icu-bsi caused by esbl-pe, and those associated with mortality at days. patients and methods: we retrospectively studied icu-bsi in the medical-surgical intensive care unit of the cayenne general hospital, during months (january to june ). we assessed survival at days from the diagnosis of icu-bsi. results: icu-bsi was diagnosed in . % of admissions giving a density incidence of . icu-bsi/ days. the median delay to the first rationale: necrotizing soft tissue infections (nsti) are a heterogenous group of severe infections. among them, group a streptococcal (gas) infection represent a subgroup that could benefit from specific therapies targeting the toxinic pathway, such as intravenous immunoglobulins or clindamycin. nevertheless, previous trials evaluating these treatments suffered from a low rate of gas infection among the study population. early identification of patients at high risk of gas infection would allow for assessing targeted treatment strategies. patients and methods: we conducted a secondary analysis of a previously published cohort of patients admitted to our tertiary center for surgically proven nsti between and . admission characteristics and microbiological documentation based on surgical samples, blood cultures or subcutaneous puncture were recorded. we compared patients with a documented gas infection to all other patients regarding admission characteristics. a generalized linear regression model was used to identify admission characteristics associated with a subsequent documentation of gas infection. results: among patients, ( %) had a gas infection, which was monomicrobial in ( %) cases. admission characteristics associated with gas infections by univariate analysis were nsaid treatment before admission ( ( . %) for gas infections vs ( . %) for others, p = . ) and leukocytosis as a continuous variable ( , /mm [ , - , ] vs. , [ - , ], p = . ). those inversely correlated with gas infections were immunodeficiency ( ( %) vs. ( . %), p = . ), and an abdominoperineal topography ( ( . %) vs. ( . %), p > . ). after multivariate analysis only immunodeficiency (or = . [ . - . ], p = . ) and an abdominoperineal infection (or = . [ . - . ], p = . ) remained associated with the absence of gas infection. using these criteria allowed for identifying subgroups of patients with increased likelihood of gas infections: from % overall (n = ) to % for non-abdominoperineal infections (n = ), % for patients without immunodeficiency (n = ) and % for both non abdominoperineal infections in patients without immunodeficiency (n = ). a sensitivity analysis for monomicrobial gas infections yielded similar results with the addition of younger age and non-nosocomial infections as predictors. conclusion: upon admission, the absence of immunodeficiency and of an abdominoperineal infection in nsti patients were covariables associated with gas infection. compliance with ethics regulations: yes. rationale: sickle-cell disease is the most common genetic disorder in the world. a complication of this disease is the acute chest syndrome (acs) which is associated with a high risk of death. respiratory tract infections are often mixed up and the introduction of betalactam antibiotics is recommended. glomerular hyperfiltration is common and responsible of a high risk of underdosing. this study compares cefotaxim continuous infusion to intermittent bolus in adult patients with acs. patients and methods: this observational retrospective monocentric study included acs admitted in intensive care unit and treated by cefotaxim with at least one plasmatic dosing between may and august . results: thirty patients received bolus administration while the others received continuous infusion. we observed patients ( %) and patients ( %) with a cefotaxim trough level ≥ mg/l in the bolus and continuous group, respectively (p < . ). the median residual concentration was mg/l [ - ] and . mg/l [ . - . ] in the bolus and continuous group, respectively (p < . ). there was no toxic effect induced by overdosing of cefotaxim. conclusion: compared to intermittent bolus infusion, continuous cefotaxim administration maximizes the pharmacokinetics parameters by obtaining a plasmatic concentration times above the minimal inhibitory concentration of usual germs associated with acs. continuous infusion of time-dependant antibiotics seems to decrease the risk of underdosing in patients with sickle cell disease. compliance with ethics regulations: not applicable. (n = , %), followed by esophageal varices rupture (n = , %), ulcer bleeding (n = , %) and diverticular hemorrhage (n = , %). infectious diseases were diagnosed in three patients ( %), including one clostridium colitis, one erosive gastritis with helicobacter pylori and one esophageal candidiasis. conclusion: gib is associated with a high mortality rate in immunocompromised patients, especially in patients with hematological malignancies. specific malignant lesions were the main etiology and may be difficult to treat. comparison with critically ill non-immunocompromised patients with gib will help physicians to provide specific therapeutic strategies in this population. compliance with ethics regulations: yes. risk factors for delayed defecation and impact on outcome in critically ill patients: a multicenter prospective non-interventional study benoît painvin ,* , arnaud gacouin , antoine roquilly , claire dahyot-fizelier , sigsimond lasocki , chloe rousseau , denis frasca , philippe seguin anesthésie-réanimation/chu rennes, rennes, france; réanimation médicale/chu rennes, rennes, france; réanimation chirurgicale/ chu nantes, nantes, france; réanimation chirurgicale/chu poitiers, poitiers, france; anesthésie-réanimation/chu angers, angers, france; centre investigation clinique/chu rennes, rennes, france; anesthésie-réanimation/chu poitiers, poitiers, france; réanimation chirurgicale/chu rennes, rennes, france correspondence: benoît painvin (painvinbe@gmail.com) ann. intensive care , (suppl ):p- rationale: delayed defecation is very common in intensive care units (icu) and it increases length of mechanical ventilation (mv), icu length of stay (los) and possibly mortality. the objective of this prospective multicenter study was to determine risks factors for constipation in icu and to evaluate their impact on mortality. patients and methods: it was a prospective multicenter non-interventional trial performed in university icus in france from january to october . all patients ≥ years old who had an expected los of days and mechanically ventilated for at least days were eligible. defecation was defined as the time of the first stool passage. results: patients were included in the analysis. a stool passage was observed in % of the patients during their icu stay with a mean delay of ± days. in multivariate analysis, risk factors for delayed passage of stool were non-invasive ventilation use and time spent under invasive ventilation whereas alcoholism, laxative treatment (before and after icu admission) and nutrition ≤ h favoured passage of stool (table ) . no relations between constipation and mortality were found. conclusion: we highlighted new and important independent factors for constipation in critically ill patients leading to a better prevention of this phenomenon.. compliance with ethics regulations: yes. rationale: community peritonitis is a frequent medical-surgical emergency of the adult, acquired by the patient in a non-hospital setting. careful multidisciplinary care is essential, involving surgeons, anesthetists, microbiologists and radiologists. the objective of our study is to determine the bacteriological aspects of intra-abdominal sepsis, to describe their sensitivity profiles and to propose treatment regimens for the management of community peritonitis. we conducted a descriptive retrospective study spanning a period of two years from january to january involving cases of community abdominal sepsis operated in the operating room of surgical emergencies of our hospital. we included in our study adult patients admitted for suspected or confirmed abdominal sepsis who had undergone bacteriological examinations on the abdominal collections. samples taken are sent directly to the bacteriology laboratory for bacteriological analysis of the results. the studies showed the mean age is . years old, with a sex ratio of . . we found positive results mainly of peritoneal origin with a percentage of . % peritonitis, dominate by intestinal peritonitis . % followed by the appendicular origin . % then peritonitis by perforation of ulcer. the most incriminated organism in intraabdominal sepsis is e. coli with a percentage of . % of the total germs found, followed by streptococcus spp . %, enterococci . %, non-fermenting bgn composed mainly of pseudomonas aeruginosa . %, staphylococci . % and acinetobacter baumanii . %. note also the presence of bacteroides fragilis is %. e. coli had a very low sensitivity profile for amoxicillin/clavulanic acid ( . %), unlike ceftriaxone, gentamicin, amikacin and ertapenem, which had a sensitivity of . %, respectively. . %, %, . %. conclusion: knowledge of the bacterial ecology of intraabdominal sepsis is important in the choice of probabilistic antibiotherapy, pending bacteriological findings. no data are yet available about nutritional management and risk of malnutrition in tunisian medical intensive care units (icu). the purpose of this study was to describe nutritional management in medical intensive care patients and to evaluate the risk of malnutrition. patients and methods: we conducted a prospective observational cross-sectional study in medical icus all around the tunisian country on the th september . all participant units received a questionary form about routine nutritional management and data of all patients hospitalized in icu on the study day. collected data were: demographic characteristics, reason for admission, severity scores and subjective evaluation of nutritional status on admission, type and volume of nutritional support on the study day and the day before, nutritional status, nutric score and biological data on the study day, reasons for nutritional interruption and other supports prescribed. results: thirteen icu all around tunisia participated to the study. no icu had a nutrition team and only one had a written nutrition protocol. four icus evaluated systematically the nutritional status on admission. all icus were aware and practiced early enteral nutrition in patients unable to maintain oral intake with a systematic supplementation of oligoelements and minerals. neither target energy nor protein intake were calculated. on the study day, patients were hospitalized with an occupation rate of %. mean age was ± years. mean body mass index was ± and % of patients were judged well nourished. enteral nutrition support was prescribed on admission in % of cases with a mean caloric intake of ± kcal/day. the mean caloric target on the study day was ± kcal/day with a mean caloric intake of ± kcal/day and a mean caloric gap of ± kcal/day. the mean nutric score and body mass index on the study day were ± and ± respectively. twenty patients were judged malnourished by the nutric score and twenty two by clinical evaluation. a good correlation was found between nutric score and clinical evaluation of nutritional status (k = . ). conclusion: tunisian icus don't have nutrition team or nutritional written protocol. early enteral feeding and supplementation is common. a good correlation exists between nutric score and clinical nutrition status evaluation. compliance with ethics regulations: yes. rationale: whether more intensive glycemic control (gc) is beneficial or harmful forcritically ill patient has been debated over the last decades. gc has been shown hard to achieve safely and effectively in intensive care. the associated increased hypoglycemia and glycemic variability is associated with worsened outcomes. however, modelbased risk-based dosing approach have recently shown potential benefits, improving significantly gc safety and performances. the stochastic targeted (star) gc framework is a model-based controller using a unique risk-based dosing approach. star identifies modelbased patient-specific insulin sensitivity and assesses its potential variability over the next hours. these predictions are used to assess hypoglycemic risks associated with a specific insulin and/or nutrition intervention to reach a specific target band. this study analyzes preliminary clinical trial results of star in a belgian icu compared to the local standard protocol (sp). the mean age in our series was . years with a male predominance (sex ratio = . ). the main revealing symptoms were epigastralgia, weight loss and vomiting. subtotal gastrectomy was performed in . % of cases and total gastrectomy in . % of cases. curative resection could only be performed in . % of cases. operative mortality was . % and morbidity was . %. the main factor influencing operative mortality was age greater than years. in univariate analysis the main prognostic factors; tumor size, degree of parietal invasion, presence of ganglionic invasion, presence of more than ganglia invaded, presence of metastases, locally advanced tumor, tumor stage and curative nature of resection. patient-related factors such as age associated blemishes and biological factors have a significant influence on the patient's prognosis. the prognosis of gastrectomies, although it has improved overall, remains mediocre. the only way to improve the prognosis remains the early diagnosis with an effective surgical management and the introduction of an adapted resuscitation. compliance with ethics regulations: yes. efficacy of multiple second line agents in refractory status epilepticus in a pediatric intensive care unit lea savary, claire le reun chu tours, tours, france correspondence: lea savary (lea.savary@hotmail.com) ann. intensive care , (suppl ):p- rationale: convulsive status epilepticus (cse) is the most common neurological emergency in children. refractory status epilepticus (rse) occurs whenseizures are not controlled with first-and secondline agents. in adults, rse requires pharmacological induced coma. in pediatric patients, association of second line treatment is often used to avoid general anesthesia although there is currently no data on the efficacy of this association. we performed a monocentric retrospective study to assess the efficacy of multiple second line agents in pediatric rse. all children admitted to clocheville hospital (tours) between january and december with a diagnosis of rse were included. our population was divided into two groups: need of general anesthesia (midazolam+) or not (midazolam-). results: children were included ( in group midazolam+, in group midazolam−) during the study period. among the patients with multiple second line agents, % did not need general anesthesia (n = ). in group midazolam+, cse was % longer in patients treated with multiple second line agents ( rationale: drowning is an acute respiratory failure resulting from immersion or submersion in a liquid. patients and methods: we report cases of drowning collated in the pediatric reanimation department during a period from to . the aim of our retrospective study was to analyze and compare the different epidemiological, clinical, parcalinical, therapeutic and evolutionary of drowning in our study. results: our study contains boys and girls, with a sex ratio (m/f) of , in an age between months and years. for cases studied, no one was classified stage i, . % classified stage ii, % stage iii, and . % stage iv. all cases collected by ou service were victim of accidental drowning, . % were secondary to the lack of parental supervision. among cases, had respiratory complications, cases of hydroelectrolytic disorders, case with infectious complications, cases of neurological and cases of cardiac or hypothermic complication. in our study, cases recovered well and cases died. the survival of the drowned person depends on the speed and efficiency of the intervention, which in thefirst place is prehospital, thus ensuring the first actions at the scene of the accident, which will have repercussions on the hospital care. this has an equal share in the improvement of the victim's prognosis. compliance with ethics regulations: not applicable. epidemiology of severe pediatric trauma following winter sport accidents in the northern french alps emilien maisonneuve , nadia roumeliotis , pierre bouzat , guillaume mortamet chu grenoble, grenoble, france; chu sainte-justine, montréal, canada correspondence: emilien maisonneuve (emilienmaisonneuve@orange. fr) ann. intensive care , (suppl ):p- rationale: this study describes the epidemiology of severe injuries related to winter sports (skiing, snowboarding and sledding) in children, and assesses potential preventive actions. we did a single-center retrospective study in our pediatric intensive care unit in the french alps. we include all patients less than years old, admitted to the intensive care unit following a skiing, snowboarding or sledding accident from to . results: we included patients (mean age . years and % were male); of which ( %), ( %) and ( %) had skiing, snowboarding and sledding accidents, respectively. the average iss (injury severity score) was . the major lesions were head (n = patients, %) and intra-abdominal (n = patients, %) injuries. compared to skiing and snowboarding, sledding accidents affected younger children ( vs. years, p < . ); most of whom did not wear a helmet ( % vs. %, p < . ). severity scores were similar amongst winter sports (iss = for skiing, for snowboarding and for sledding accident, p = . ). rationale: best strategies for the management of severe pediatric traumatic brain injury (tbi) are still not clearly established and wide variations among professional practices have been reported in the literature. unfortunately, these variations in practice have an impact on the patient's outcome. the objectives of this work were to assess the adequacy of professional practices to the guidelines for the management of severe head injury and to assess the level of agreement of respondents in the absence of guideline. patients and methods: a practice survey was conducted in frenchspeaking hospitals in canada, belgium, switzerland and france from april st to june th, . the survey was conducted as a progressive clinical case with questions based on guidelines and the literature from to . the questions related to the assessment and management of tbi during the acute and intensive care phase. results: seventy-eight questionnaires were included. the adherence to guidelines was good, with items out of obtaining an adherence rate of more than % regardless of the annual number of tbi managed by the centre. there was strong agreement among clinicians on the intracranial pressure (pic) (> %) and cerebral perfusion pressure (> %) thresholds used according to age. guidelines for indication of pic monitoring were almost perfectly followed in the case of glasgow score < and abnormal brain ct scan (n = , %). on the other hand, the natremia and glycemia thresholds and the role of transcranial doppler were not consistent. strong adherence to recent recommendations was achieved: seizure prophylaxis with levitracetam (n = / , %) and capnia threshold (n = , %). assessment of o pressure in brain tissue (n = , %) and autoregulation (n = ; %) was not a common practice. conclusion: overall, practices for the management of tbi appear to be standardised. variations persist in areas where there is a lack of literature and guidelines in paediatrics, so clinicians seem to refer to adult guidelines. compliance with ethics regulations: yes. choubeila guetteche chu constantine, constantine, algeria correspondence: choubeila guetteche (cguetteche@gmail.com) ann. intensive care , (suppl ):p- rationale: ingesting a coin cell is a common household accident in children, which can have serious consequences. the goal is to determine prognostic factors to improve management and reduce complications. patients and methods: we conducted a retrospective study including children under admitted in pediatric intensive care between january and may for ingestion of button cells, with epidemiological, clinical and paraclinical data collection. results: twenty-six children boys ( %), and girls ( %) were included, with an average age of months ( - ), increased incidence in recent years. clinical signs indicative were dysphasia with hyper-sialorrhea in cases, cervical pain in one case, respiratory distress in one case, the cell was located in the upper third of the esophagus in cases, third average in cases, third inferior in cases, the mean time before extraction was h. complications: cases of mediastinitis, cases of oesotracheal fistula, a case of perforation. conclusion: the young age of the child, the diameter of the battery, and especially the time of care are risk factors for the occurrence of complications, the prevention passes through the education of the general public and creation of channel of taking into account fast charge. compliance with ethics regulations: not applicable. yacine benhocine university hospital center nedir mohamed, tizi-ouzou, algeria correspondence: yacine benhocine (yacine @yahoo.fr) ann. intensive care , (suppl ):p- rationale: inhalation of foreign bodies is a common and serious accident in children, especially between and years old. at this age, children use their mouth to explore their environment. asphyxia is the immediate risk and respiratory sequelae may appear secondarily. the severity of this incident has been considerably reduced due to the progress of the instrumentation and anesthesia which condition the smooth running of the therapeutic act. aim: to evaluate the anesthetic modalities of the extraction of the foreign bodies of the airways in children, in order to optimize our care with a maximum of security. a prospective, mono-centric, descriptive study from january to november of patients treated for inhalation of foreign bodies in the airways. study population wasdefined by: age, sex, hospitalization context, physical and radiological examination data, anestheticmanagement. results: the average age of the patients was . months, the male predominated ( %), and the hospitalization context was polymorphic. general anesthesia was necessary in all cases, sevoflurane mainly for narcosis; the combination of an opioid in . % of cases and a curare in . %. spontaneous ventilation is desirable, but % was manually broken down intermittently between extraction attempts. cases of desaturation, bronchospasm, bradycardia, and pneumothorax have been reported. . % had a good evolution. discussion: the results of the epidemiological data are consistent with those of the literature. the penetration syndrome is very revealing. the chest x-ray is the key examination, the diagnosis is often based on indirect signs. in case of asphyxia by foreign body enclosed above or between the vocal cords, laryngoscopy and oxygenation is the first step to perform. in other cases, a rigid bronchoscopy is performed under general anesthesia; inhalation induction with sevoflurane is the technique of choice for many experienced authors. controlled ventilation is used in the majority of cases because spontaneous ventilation is not often not possible. the heterogeneity of anesthetic practices accounts for the multiplicity of clinical situations. conclusion: the inhalation of a foreign body is a diagnostic and therapeutic emergency. extraction of the foreign body takes place under general anesthesia, which is difficult and at risk. compliance with ethics regulations: yes. non-invasive neurally adjusted ventilatory assist (nava) in infants with bronchiolitis: a retrospective cohort study alex lepage-farrell, sally al omar, atsushi kawaguchi, sandrine essouri, philippe jouvet, guillaume emeriaud chu sainte justine, université de montréal, montréal, canada correspondence: alex lepage-farrell (alex.lepage-farrell@umontreal.ca) ann. intensive care , (suppl ):p- rationale: bronchiolitis is one main reason for admission to pediatric intensive care unit. most infants are successfully managed with nasal cpap or high-flow nasal cannula, but about a third of these patients are not sufficiently supported and require an alternative support. non-invasive neurally adjusted ventilatory assist (niv-nava) improves patient-ventilator interactions and could therefore improve the effectiveness of non-invasive support. our hypothesis is that niv-nava is feasible in infants with bronchiolitis and that it reduces the respiratory effort. patients and methods: we retrospectively studied all patients under years of age with a clinical diagnosis of bronchiolitis ventilated with niv-nava in our pediatric intensive care unit, between october and june . patients characteristics, respiratory and physiologic parameters, including diaphragmatic electrical activity (edi) were extracted from an electronic medical database (data collected every s). respiratory effort was estimated using the modified wood clinical score for asthma (mwcas) and the inspiratory peak edi, and -h periods before and after niv-nava initiation were compared (wilcoxon rank test). the study was approved by the local research ethics committee. results: during the study period, patients were admitted with bronchiolitis; infants ( boys) with a median ( th- th percentile) age of ( - ) days were treated with niv-nava after a failure of other non-invasive support methods, and all were included. twentyfive subjects ( %) had at least one comorbidity. the interfaces used were predominantly face masks ( %). the maximum ventilatory settings were nava level of . ( . - . ), peep of ( - ) cmh o, fio of % ( - ) and maximal pressure of ( - ) cmh o. total duration of non-invasive ventilation was ( - ) hours, including ( - ) hours in niv-nava. as detailed in the table , mwcas significantly decreased after niv-nava initiation, from . ( . - . ) to . ( . - . ), p < . . a decrease in inspiratory peak edi was also observed, which was particularly clinically relevant in infants with high baseline edi (> mcv). capillary blood ph and pco also significantly improved after niv-nava introduction. six patients ( %) needed escalation to endotracheal intubation. conclusion: this study confirms the feasibility of niv-nava in infants with bronchiolitis after failure of first line non-invasive support, with a low failure rate. niv-nava initiation was followed by a decrease in respiratory effort and an improvement in blood gases. this observational study supports the needs for prospective interventional trial. compliance with ethics regulations: yes. rationale: the use of blood transfusion is frequent in pediatric intensive care units and has increased significantly since . considered as therapeutic, it requires an assessment of the benefit / risk balance before making the transfusion decision. the aim of our study is to describe the transfusion practices in the pediatric resuscitation department of the ehs canastel, algeria. patients and methods: a retrospective observational study over a -month period from january of any blood transfusion performed in hospitalized patients, in the pediatric intensive care unit. we studied : the age, the sex, the history of blood transfusion, the indication of transfusion, the haemodynamic and respiratory parameters, the transfusional accidents, the length of stay in intensive care, the evolution after a blood transfusion. results: these included transfusion patients out of hospitalizations during the -month period, mean age was months.all patients had no transfusion history, % of patients had their anemia admission and % developed it during their stay. the reason for hospitalization was respiratory distress in %, convulsive condition in %, polytrauma in %, and head trauma in %. the indication of the transfusion was placed on a hb inferior or equal to g / dl in % of cases, in % on an hb superior to g / dl in addition to the clinical criteria of intolerance to anemia; in % of the cases no clinical or biological criteria found, the nature of the blood products was of the red cell in % of the cases and of the plasma concentrate in / of the cases and pfc in %. % received a+, % of a-, % of b+, % of o+ and % of o-. % of the patients had a transfusion-like reaction at min after the start of the transfusion; % of the patients were under artificial ventilation and % were under hemodynamic support, % under diuretic.the average length of stay was days; the favorable outcome was % of the patients after the transfusion with an increase in the hb level beginning, % of the patients had complications of their pathology and the death in % of the cases. conclusion: current transfusion practices in children often do not reflect the implementation of our current knowledge of the need for transfusion. hence the need to review the protocols and practice other transfusion alternatives to avoid complications and improve the quality of care. compliance with ethics regulations: not applicable. rationale: bacterial multi drug resistance is medical actuality nowadays, because of its morbidity and mortality especially in intensive care, it constitutes a real problem in our hospitals. we conducted a retrospective descriptive study, to identify bacterial drug resistance profile of patients with cross infections in the department of intensive care in august hospital. this study included patients hospitalized between st january and st december . the data was collected from medical records of this unit as from the register of the bacteriology service of ibn rochd university hospital. results: patients were hospitalized in the resuscitation service, of which had nosocomial infection, an incidence of . %. the mean age of the patients was years with male predominance (sex ratio . ), the average stay in intensive care was days. the site of infection was pulmonary in % of cases, blood in % of cases, urinary in % of cases, central catheter in %, neuro-meningeal in . % of cases. the germs isolated were: acinetobacter baumanii in . % of cases, pseudomonas aeroginosa in . % of cases, klebsiella pneumonia in . % of cases, enterococcus feacalis in . % of cases, e.coli in . % of cases and staphylococcus aureus in % of cases. acinteobacter baumanii showed resistance rates of up to % for the impenem and % for amikacin. regarding pseudomonas, it was resistant to impenem in % of cases and in % of cases to amikacin. compared to klebsiella, resistance to imipenem was % and % for amikacin. the mortality rate of infected patients was % conclusion: in the light of this work, we found that important emergence of multidrug resistance bacteria in intensive care unit is related to not only the immunocompomised state of patients but also to daily bad practices of health professionals such as the misuse of antibiotics. compliance with ethics regulations: yes. overnight culture of escherichia coli, klebsiella pneumoniae, staphylococcus aureus and pseudomonas aeruginosa, was also sequenced. results: twenty-four samples and the pc were analyzed. amplicon sequence analyses found similar results with the two primer pairs in % of cases. cultured pathogen was found in % ( / ) for human primer pair and in % ( / ) for earth primer pair. for each eta, ngs revealed bacteria unknown as pathogen globally identified as oropharyngeal flora in conventional microbiology (table ) . alpha diversity decreased for all vap patients overtime, average shannon . ( ; . ) versus ( . ; . ), and was higher in upper respiratory tract (os) versus lower respiratory tract (eta): average shannon . ( . ; . ) vs. . ( . ; . ) (ns). conclusion: this pilot study highlights the impact of s rdna amplification procedures (especially oligonucleotide sequences) used on the results in microbiome research. concordance between ngs and bacterial culture, as well as similar evolution of the alpha diversity than previously described ( ), enables us to validate our methodology using the "gut primers" pair f- r. these findings allow furthers major studies on the pulmonary microbiome of icu ventilated patients including comparison according to the occurrence of a vap or not. compliance with ethics regulations: yes. rationale: in the field of intensive care only few studies have explored bacterial microbiota whereas virome remained hardly considered. it appears essential to describe both evolution in mechanically-ventilated patients to improve the pathophysiological understanding of ventilator-associated pneumonia (vap) development. to date no study had been simultaneously conducted on lower respiratory tract with a single nucleic acid extraction before metagenomics analysis of bacterial microbiota and virome. we conducted a preliminary study to validate our methodology based on a common automated extraction of nucleic acids. patients and methods: twelve mechanically ventilated patients were selected: five who developped (vap) and seven controls (c) who did not. endotracheal aspirate (eta) were collected between intubation and day (or dvap for vap patients). conventional bacterial microbiology and multiplex respiratory viruses pcr were also performed. total nucleic acids were extracted using nuclisens easymag extractor. for the bacterial microbiota, region v of the s rrna genes was amplified. for the virome, the nextera dna xt kit (illumina) and rna seq trio kit (nugen) protocols were used to prepare viral dna and rna libraries. libraries underwent paired-end sequencing on the illumina miseq (bacteria) or nextseq- (virus) platform. after bioinformatics analysis we compared the performance of metagenomics analysis with conventional bacterial culture and other common viral detection methods. results: for culturable bacteria, concordance between conventional microbiology and sequencing was found in % ( / table . our preliminary results confirm the feasability of exploring both bacterial microbiota and virome on the same sample using a common extraction method. data from metagenomics were highly concordant with conventionnal detection methods for known pathogenic viruses and bacteria in lower tract respiratory sample and enables identification of other microorganisms. this is the first step for a large cohort study that aims to compare evolution of global lung microbiome in patients at risk of vap and assess how bacteria and virus interplay. compliance with ethics regulations: yes. references . clancy department of medical and toxicological critical care, lariboisière hospital one microorganism was isolated in . % and two in . % of cases. the main isolated microorganism were enterobacteriaceae in . % of patients. they were esbl-producers in . % of cases. initial antibiotic therapy was appropriate in . % of cases. factors independently associated with esbl-pe as the causative microorganism of icu-bsi were esbl-pe carriage prior to icu-bsi the sensitivity of esbl-pe carriage to predict esbl-pe as the causative microorganism of icu-bsi was . %, and specificity was . %. mortality at days was . % in the general population in multivariable analysis, there was no parameter which was independently associated to mortality at day from the occurrence of icu-bsi. conclusion: icu-bsi complicates . % of admission to icu and was associated with % in-hospital mortality assessing and applying individualized treatment for group a streptococcal necrotizing soft-tissue infection is possible service de réanimation médicale intensive care decompressive craniectomy in traumatic brain injury: about cases karama bouchaala sex ratio of . . the mean (sd) length of stay in icu was . ± . days. the mean glasgow coma score (gcs) (sd) was . ± . and gcs ≤ in . %. sofa score > was found in patients ( . %) and sapsii score ≥ in patients ( . %). the cerebral ctscan at admission showed acute subdural hematoma (asdh) in ( . %), cerebral oedema ( . %) and cerebral contusions ( %) teaching: fresenius medical care; patent or product inventor: gml czech republic banydeen rishika: no conflict of interest baptiste amandine: no conflict of interest baptiste olivier: no conflict of interest barbar saber davide: no disclosure barbier françois: no disclosure barbierlouise: trainings, teaching: ethicon, astellas; invitation to national or international congresses: sandoz, astellas barnerias christine: no disclosure baron aurore: no disclosure baron elodie: no conflict of interest barr att -due andreas: no disclosure barrau stephanie: no disclosure barraud damien: no disclosure barraud helene: no disclosure barrois brigitte: no conflict of interest baruchel andré: no disclosure bastide marie anaïs: no conflict of interest baudel jean-luc: no conflict of interest baudin florent: invitation to national or international congresses: dr baudin has received speaking fees from maquet critical care (epnv teaching: drager; invitation to national or international congresses: msd; hill rom beganton frankie: no conflict of interest begot erwan: no disclosure beinse guillaume: research support/scientific studies: association pour la recherche contre le cancer ion and fresenius kabi bensaid abdelhak: no disclosure bensardi fatimazahra: no disclosure benyamina mourad: no disclosure benzerara laurent: patent or product inventor: aphp benzerdjeb nazim: research support/scientific studies: amarape, icap; consultancy, expert: alphasights, msd; trainings, teaching: msd beqiri erta: no disclosure bÉranger agathe: no conflict of interest berard emilie: no conflict of interest berdai adnane: no disclosure berger patrick: no disclosure bernal william: no disclosure bernardin gilles: no disclosure berrada lina: no conflict of interest berthaud romain: no conflict of interest berthet guillaume: no conflict of interest berti enora: no conflict of interest bertoli sarah: no disclosure bertrand pierre-marie no conflict of interest besbes lamia: no disclosure besbes mohamed: no conflict of interest besch camille: invitation to national or international congresses: abbvie no conflict of interest boisseau chloé: no disclosure boissel nicolas: no disclosure boissier florence: no conflict of interest boivin alexandra: no conflict of interest bonacorsi stéphane: no conflict of interest bongiovanni filippo: no conflict of interest bonnardel eline: no conflict of interest bonnefoy-cudraz eric: no disclosure bonnet sixtine: no conflict of interest bonnevie tristan: research support/scientific studies invitation to national or international congresses: fresenius kabi and fresenius medi-calcare bucur petru: no disclosure buetti niccolo: research support/scientific studies: swiss national science foundation research grant and bangerter rhyner foundation supporting my postdoc bui hoang-nam: no disclosure burelli gabrielle: no conflict of interest burgel pierre-régis: no disclosure burghi g: no conflict of interest bustarret olivier: no conflict of interest butin-druoton anne-lise: invitation to national or international congresses expert: astra-zeneca; invitation to national or international congresses expert: hamilton medical; invitation to national or international congresses: hamilton medical chemli wael: no conflict of interest chenouard alexis: no conflict of interest cherkab rachid: no conflict of interest chevret sylvie: no disclosure chhun stephanie: no conflict of interest chiche jean-daniel: no disclosure chicoisneau maxence: no conflict of interest chlilek abdelaziz: no disclosure chocron richard: consultancy, expert: aspen chommeloux juliette: no conflict of interest chomton maryline: no conflict of interest chosidow olivier: no disclosure chouchana laurent expert: biotest; invitation to national or international congresses: sanofi research support/scientific studies: fresenius medical care; consultancy, expert: fresenius medical care; invitation to national or international congresses: xenios novalung, heilbronn, germany dachraoui fahmi: no disclosure dahoumane redouane: no conflict of interest dahyot-fizelier claire: no disclosure daix thomas: no conflict of interest daly foued: no conflict of interest damonti lauro: no conflict of interest dantan etienne: no conflict of interest darmon michaël: research support/scientific studies: msd no disclosure das vincent: no disclosure daubin cedric: no conflict of interest daubin delphine: no conflict of interest daudon michel: no disclosure daufresne pierre: no conflict of interest dauger stéphane: no conflict of interest daviet florence: invitation to national or international congresses: sandosz de courson hugues: no conflict of interest de jong audrey: trainings, teaching: baxter, medtronic; invitation to national or international congresses teaching: cardiosleep delhaes laurence: no disclosure delignette marie-charlotte: no conflict of interest dellamonica jean: trainings, teaching: medtronic; invitation to national or international congresses: msd, general electrics delpierre clément: no conflict of interest delville marianne: no conflict of interest demailly zoé: research support/scientific studies: srlf demarest elsa: no disclosure demaret pierre: no conflict of interest demiselle julien: no conflict of interest demondion pierre: no conflict of interest demoule alexandre: research support/scientific studies: drager, philips; consultancy, expert: baxter, respinor, lungpacer; trainings, teaching: fisher & paykel, hamilton, baxter; invitation to national or international congresses: fisher & paykel denis manon: no conflict ofinterest depeyre fanny: invitation to national or international congresses: pfizer deplante yvon: no conflict of interest dequin pierre-françois: research support/scientific studies: medimmune combioxin ferring pharmaceuticals a/s asahi kasei pharma america corporation derauglaudre lucie: no conflict of interest derbel karim: no disclosure derkaoui ali: no disclosure dervin krystel: no conflict of interest desaive thomas: no conflict of interest desguerre isabelle: research support/scientific studies: ptc inc, avexis; consultancy, expert: avexis, ptc inc, biogene; trainings, teaching: roche, ptc inc, avexis; invitation to national or international congresses: sarepta, biogen, avexis, biomarin desnos cyrielle: no conflict of interest desroys du roure françois: no conflict of interest detollenaere charles: no conflict of interest devaquet jérôme: invitation to national or international congresses expert: lungpacer; invitation to national or international congresses: lungpacer dreyfuss didier: research support/scientific studies: grant from french ministry of health drouot xavier: no disclosure du cheyron damien: no conflict of interest dubÉ bruno-pierre: consultancy, expert: novartis, gsk dubert marie: no conflict of interest dubost baptiste: no conflict of interest dubost jean-louis: no conflict of interest duburcq thibault: no conflict of interest duchemann boris: consultancy, expert: bms, msd, roche; invitation to national or international congresses no conflict of interest frÉrou aurélien: no conflict of interest fritz caroline: no disclosure fromentin mélanie: research support/scientific studies: msd; invitation to national or international congresses: msd frouin antoine: no conflict of interest frugier alexandre: no disclosure gaboriau louise: no conflict of interest gaci rostane: invitation to national or international congresses: bard gacouin arnaud: no disclosure gaddas mehdi: no conflict of interest gaillard arnaud: trainings, teaching: zoll medical gaimard sophie: no conflict of interest gainnier marc: no conflict of interest galbois arnaud: no conflict of interest galerneau louis-marie: invitation to national or international congresses: agir À domicile galicier lionel: consultancy, expert: novartis, eusapharma; trainings, teaching: baxalta, pfizer; invitation to national or international congresses no conflict of interest ichaÏ philippe: no conflict of interest imen sioud: no conflict of interest ioos vincent: no disclosure iserin franck: no disclosure issa nahema: no conflict of interest jaber samir: consultancy, expert: drager, fisher-paykel; medtronic; baxter xenios fresenius; invitation to national or international congresses: drager no conflict of interest jacq gwenaëlle: no conflict of interest jacquet emmanuelle: research support/scientific studies: unicancer (esme and storm studies invitation to national or international congresses: pfizer université laval-qc-ca labbe vincent: no disclosure labro laura: no disclosure lacaille florence: no conflict of interest lacampagne alain: no disclosure lacan claire: no conflict of interest lacherade jean-claude: no conflict of interest ladjemi maha-zohra: no conflict of interest lafon charles: no conflict of interest lafon marie-edith: no disclosure lafon thomas: no conflict of interest lagache laurie: invitation to national or international congresses advertising documents: philips; trainings, teaching: novartis, gsk, astra zeneca, boeringher; invitation to national or international congresses: chiesi, astra zeneca, sos oxygene, novartis, boeringher lamoth frédéric: consultancy, expert: gilead, msd, basilea; invitation to national or international congresses: msd expert: norgine; trainings, teaching: fujifilm, boston scientific lebreton guillaume: no disclosure lebrun-vignes benedicte: research support/ scientific studies: novartis; consultancy, expert: ansm lebuffe gilles: no disclosure leclerc maxime: no conflictof interest lÉcluse aldéric: research support/scientific studies: pgrx avc study; consultancy, expert: bms-pfizer, boerhinger ingelheim, bayer; invitation to national or international congresses: bms-pfizer, boerhinger ingelheim ledoux didier: no disclosure lefebvre francois: no conflict of interest macloughlin ronan: research support/scientific studies: aerogen ltd no conflict of interest mari arnaud: no conflict of interest marie damien: no conflict of interest marijon eloi: no disclosure mariotte eric: consultancy, expert: sanofi-aventis marjanovic nicolas: no disclosure marjanovic zora: no disclosure maroni arielle: no conflict of interest marot benoit: no conflict of interest marque sophie: no conflict of interest marti teaching: zambon, chiesi; invitation to national or international congresses no conflict of interest matusik elodie: no conflict of interest mauchien benedicte: no conflict of interest maury eric: research support/scientific studies: doran international, drager; trainings, teaching: vygon maxime virginie: no conflict of interest mayaux julien: invitation to national or international congresses stock shareholder: tanderev; patent or product inventor: tanderev mercat alain: research support/scientific studies: fisher-paykel, general electric; consultancy, expert: faron pharmaceuticals no disclosure merhabene takoua: no conflict of interest merle jean-claude: no disclosure mesotten dieter: no conflict of interest messaadi amenallah: no conflict of interest messika jonathan: invitation to national or international congresses: cslbehring; fisher&paykel metaxa victoria: no disclosure metogo mbengono junette arlette: no conflict of interest meunier anne: no conflict of interest meurice jean-claude: no disclosure meybeck agnes: consultancy, expert: janssen, gilead; 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consultancy, expert: msd, gilead, pfizer; invitation to national or international congresses: gilead, pfizer nesseler nicolas: no conflict of interest neviere remi: no disclosure nguyen alexandre: no disclosure nguyen khoa thao: no conflict of interest nicolau-travers marie-laure: no disclosure niÉrat marie cécile: no conflict of interest nieszkowska ania: no disclosure nigeon olivier: no conflict of interest nitel gautier: no conflict of interest nodea elena madalina: no conflict of interest noel marine: no conflict of interest nogier marie-béatrice: no disclosure noorah zaid: no disclosure nouira wiem: no conflict of interest noumeir rita: stock shareholder: softmedical noury norbert: no conflict of interest novy emmanuel: research support/scientific studies: msd; invitation to national or international congresses: pfizer expert: air liquide medical system ollivier veronique: no conflict of interest onimus thierry: no conflict of interest oppenheimer anne: invitation to national or international congresses: gedeon richter orkisz maciej: no conflict of interest orliaguet gilles: research support/scientific studies research support/scientific studies: oxynov; patent or product inventor: oxynov patrier juliette: no conflict of interest paugam catherine: no disclosure paul marine: no conflict of interest paul-bellon rachel: no disclosure paulo nicolas: no conflict of interest pavot arthur: invitation to national or international congresses: fresenius medical care france pehlivan jonathan: no conflict of interest peigne vincent: invitation to national or international congresses: air liquide pÉju edwige: no conflict of interest pene frédéric: consultancy, expert: alexion pÉpin-lehalleur adrien: invitation to national or international congresses: chiesi pere morgane: no conflict of interest pereira bruno: no disclosure perez didier: no disclosure perez pierre: no disclosure perez yonatan: no conflict of interest perier françois: no disclosure perin nicolas: no conflict of interest biomerieux robin emmanuel: no conflict of interest robin nicolas: no disclosure robineau olivier: no disclosure roch antoine: no disclosure roche anne: no conflict of interest roger claire: consultancy, expert: pfizer, fre-senius medical care; 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consultancy, expert: fresenius medical care france; invitation to national or international congresses: xenios novalung, heilbronn no conflict of interest sirault bruno: no disclosure sirodot michel: no disclosure slama michel: no disclosure slim amine: no disclosure smielewski peter: no disclosure soares marcio: stock shareholder: epimed solutions teaching: gilead; invitation to national or international congresses: pfizer spagnoletti marco: no conflict of interest steckelmacher claire: no disclosure stockx luc: research support/scientific studies: phenox, medtronic; consultancy no conflict of interest voiriot guillaume: research support/scientific studies: biomérieux, sos oxygène, janssen; consultancy, expert: biomérieux; invitation to national or international congresses: biomérieux von kietzell matthias: invitation to national or international congresses expert: aguettant; invitation to national or international congresses: vifor yacoubi wejden: no conflict of interest yager hélène: no conflict of interest yahya yosra: no conflict of interest yakini khalid: no disclosure yakouben karima: no disclosure yonis hodane: invitation to national or international congresses: lvl medical et pfizer younan romy: no conflict of interest youssoufa atika: no disclosure zacharia mahi: no disclosure zafrani lara: research support/scientific studies: jazz pharmaceuticals zambon olivier: no disclosure zaouak nadia: no conflict of interest zaouche khedija: no conflict of interest zarrougui wafa: no conflict of interest ze minkande jacqueline: no disclosure zeghdoud dalila: no disclosure zerbib yoann: no conflict of interest zerhouni amel: no conflict of interest zerhouni amine: no conflict of interest zerimech farid: no conflict of interest zerouali khalid: no disclosure zheng yi: no conflict of interest zimmerli stefan: research support/scientific studies: msd, pfizer, gilead; consultancy, expert: msd, pfizer; trainings, teaching: gilead; invitation to national or international congresses springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations farhat hached hospital, sousse, tunisia; yassminet regional hospital, ben arous, tunisia; habib bougatfa regional hospital, bizerte, tunisia; larabta hospital, tunis, tunisia; carthagene private hospital, tunis, tunisia; regional hospital of zaghouan, zaghouan, tunisia; regional hospital of tozeur, tozeur, tunisia; habib thameur hospital, tunis, tunisia correspondence: samia ayed (samia.ayed@yahoo.fr) ann. intensive care , (suppl ):p- geoffroy hariri, kyann hodjat-panah, laurene blum, jean-rémi lavillegrand, idriss razach, naike bige, jean-luc baudel, bertrand guidet, eric maury, hafid ait-oufella médecine intensive-réanimation, hôpital saint-antoine, paris, france correspondence: geoffroy hariri (geoffroyhariri@hotmail.com) ann. intensive care , (suppl ):p- rationale: hemolytic anemia (ha) is a common condition in intensive care unit but its diagnosis remains challenging. free hemoglobin (and heme) degradation leads to co release that can bind to hemoglobin to form carboxyhemoglobin (hbco). we hypothesized that hbco concentration could be used as a reliable diagnosis tool for ha. patients and methods: we performed a monocentric retrospective study in a -bed intensive care unit at st antoine hospital, paris, between and . all patients hospitalized for ha with arterial hbco dosage at admission were included. arterial hbco was measured in routine in our department with an il system ph/ blood gas analyzer. demographic and biological data were collected. a group control of patients with non-hemolytic anemia (hb < g/ dl) (nha) was also included. finally, we analyzed patients outcome according to hbco changes during icu stay. results: between and , patients with ha were included. nha patients were included in the control group. patients with ha were younger than patients with nha ( [ ; ] vs. [ ; ] years old, p = . ) but admission sofa was not different between groups ( [ ; ] , vs. [ ; ] , p = ns). among patients with ha, % had thrombotic microangiopathy, % had autoimmune hemolytic anemia and % had sickle cell disease. at icu admission, ha patients had higher hbco level than patients with nha ( . [ . ; . ] vs. . [ . ; . ] %; p < . ). hbco was a reliable biomarker of hemolysis (auc . ( . ; . ) p < . ). an hbco level threshold at . % identify hemolysis with a sensitivity ( - ) % and a specificity ( - ) %. in ha group, hbco was negatively correlated to hb level (r = . ; p < . ). in ha patients, changes of hbco level during icu management were associated with outcome, decreasing in survivors ( . [ ; . ] vs. . [ . ; . ] ; p = . ) but not in non-survivors ( . [ . ; . ] vs. . [ . ; . ] %; p = . ). conclusion: carboxyhemoglobin is a reliable diagnosis and prognosis biomarker for hemolytic anemia in icu compliance with ethics regulations: yes. rationale: thrombocytopenia is the most commonly hemostatic disorder encountered in intensive care, present in to % of patients. the mortality associated with this thrombocytopenia, the numerous pathological contexts associated with resuscitation and the lack of a recommended management strategy led to the establishment of these guidelines. the aim of our study was to determine the incidence, causes and risk factors associated with the occurrence of thrombocytopenia, as well as the impact of thrombocytopenia on the mortality and length of stay in the icu ibn medical resuscitation unit. rochd de casablanca, over a period of months. patients and methods: this was a prospective study, carried out in the medical resuscitation department of ibn rochd university hospital in casablanca over a period of months. there were two groups: ''sick'' group with thrombocytopenia with a platelets count < , / mm , and a ''control'' group without thrombocytopenia. patients with previous platelet disorders, hematologic malignancies, and patients undergoing chemotherapy were excluded. of the patients included, episodes of thrombocytopenia were identified, anoverall incidence of . %. sepsis was incriminated times ( . %), followed by ards in patients ( . %), massive filling in patients ( . %), disseminated intravascular coagulation in patients ( . %), and massive transfusion in patients ( . %). the drug origin was incriminated in patients ( . %). it was due to quinolones and imipenem. the mortality rate was deaths ( . %) which was inversely proportional to the lowest platelet count in the thrombocytopenia group, compared to deaths ( %) in the control group. the mean duration of stay in the thrombocytopenia group was ± days with extremes ranging from to days. conclusion: thrombocytopenia was a common abnormality in the intensive care system, it occured in many pathological situations and was a factor of morbidity and excess mortality. the most common etiology in this study was sepsis. the diagnostic and therapeutic approach depended on the particular clinical context in which thrombocytopenia occurs. its onset may constitute a hematological emergency, particularly when there is a major mucocutaneous and / or visceral hemorrhagic syndrome, which necessitates a rapid etiological diagnosis, and the establishment of an effective treatment, both symptomatic and specific. compliance with ethics regulations: not applicable. marc pineton de chambrun , romaric larcher , frédéric pene , laurent argaud , alexandre demoule , rémi coudroy , elie azoulay , yacine tandjaoui-lambiotte , stanislas faguer , alain combes , charles-edouard luyt , zahir amoura sorbonne université, aphp, hôpital la pitié-salpêtrière, institut de cardiométabolisme et nutrition (ican), service de médecine intensive-réanimation, paris, paris, france; rationale: catastrophic antiphospholipid syndrome (caps), the most severe manifestation of antiphospholipid syndrome (aps), is characterised by simultaneous thromboses in multiple organs. diagnosing caps can be challenging but its early recognition and management is crucial for a favourable outcome. this study was undertaken to evaluate the frequencies, distributions and ability to predict mortality of "definite/probable" or "no-caps" categories of thrombotic aps patients requiring admission to the intensive care unit (icu rationale: septic acute kidney injury (s-aki) is a frequent complication in critically ill patients and is associated with high morbidity and mortality. it is well known that chronic kidney disease increases the risk of pulmonary embolism (pe), but few studies have investigated the relationship between acute kidney injury (aki) and pe occurrence in septic patients. the aim of this study is to determine whether patients with aki are at increased risk of developing pe. patients and methods: were included, in a prospective study conducted over months (january -june , ) in a medical surgical intensive care unit, all the patients older than years with septic shock at admission or during hospitalization. two groups were compared: patients with kidney injury (aki+ group) and patients without kidney injury (aki− group). we studied the occurrence of pe in these two groups. results: we included patients. the mean (sd) age was . ( ± ) years. sex ratio was . . thirty one ( . %) patients developed pe. the occurrence of pe was significantly higher in (aki + group) [ patients ( %) vs. patients ( %); p = . ]. the incidence of pe according to kidney injury severity was patients ( %) kdigo i, patients ( %) kdigo ii, patients ( %) kdigo iii. in the aki+ group, pe was significantly associated with increased sofa score at admission ( points vs. points; p = . ), lower platelets count ( , vs. , ; p = . ), higher lacatatemia at septic shock day [ . vs. . mmol/l; p = . ] and higher c reactive protein level [ mg/l vs. mg/l; p = . ]. in a multivariate analysis the pe risk factors in (aki+ group) were thrombopenia (odds ratio = . ; ci [ . - . ], p = . ) and c-reactive protein value (odds ratio = . ; ci[ . - . ], p = . ). discussion: the increased risk for pe with aki may be due to endothelial involvement, vascular injury and the related changes found in procoagulant proteins (increased levels of fibrinogen, factor vii, factor viii, von willebrand factor, and plasminogen activator inhibitor- ). in our study, lower platelet and higher c reactive protein level were found in patients with pe, suggesting the participation of disseminated intravascular coagulation. these factors may contribute to increase pe risk. conclusion: the risk of pe is higher in septic patients with aki than in those with normal kidney function. therefore, because of paucity of evidence, larger studies are needed to understand pe pathway in septic aki and to establish efficient prophylaxis protocols. compliance with ethics regulations: yes. and of these patients ( . %) required intensive care. the lasted were males ( %) and a majority ( %) were younger than years of age. in intensive care patients, only ( . %) had nosocomial infection, majority were community acquired infections ( . %) with ( %) pneumoniae, ( . %) profound abscess, pyelonephritis ( . %), ( %) meningitidis. patients( %) required mechanical ventilation for days ( % ci - ), length of stay in icu was days ( % ci - ) and mortality rate was %. conclusion: hmkp infections lead young patients in intensive care unit in one third of case with a majority of pneumoniae requiring mechanical ventilation and with a high rate of mortality. furthers studies are needed to investigate the role of this particular strain in severity. compliance with ethics regulations: yes. rationale: infections secondary to snakebite occur in a number of patients, and are potentially life-threatening. bothrops lanceolatus bites in martinique average thirty cases per year and may result in severe thrombotic and infectious complications. we aimed to investigate the infectious complications related to bothrops lanceolatus bite. patients and methods: a retrospective single-center observational study over seven years ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) was carried out, including all patients admitted to the hospital due to bothrops lanceolatus bite. clinical and biological data were reported using the dx care, x-plore et cyberlab softwares of the emergency medicine and analyzed. one hundred and seventy snake-bitten patients ( males and females) were included. thirty-nine patients ( %) presented grade or envenoming. twenty patients ( %) developed wound infections. the isolated bacteria were aeromonas hydrophila ( cases), morganella morganii ( cases), group a streptococuss, and group b streptococcus (one case each). patients were treated empirically with third-generation cephalosporin (or amoxicillin/clavulanate), aminoglycoside and metronidazole combinations. outcome was favorable. the main factor significantly associated with the occurrence of infection following snakebite was the severity of envenoming (p < . ). our findings clearly point towards the frequent onset of infectious complications in b. lanceolatusbitten patients presenting with grade and envenoming. conclusion: infectious bite-related complications of bothrops lanceolatus account for approximately % of the cases, with a strong predominance for grade iii and iv. thus, based on the bacteria identified in the wounds; we suggest that empiric antibiotic therapy including third-generation cephalosporin should be administered to those patients on hospital admission. compliance with ethics regulations: yes. rationale: endocrine abnormalities have been reported with varying frequencies, following traumatic brain injury (tbi). few studies have examined the clinical features and outcomes of isolated acute thyrotropic hormone deficiencies after tbi. theaim of the study was to evaluate the early changes in thyrotropic hormone levels after traumatic brain injury (tbi) and to evaluate whether hormone changes are related to outcome patients and methods: we conducted a months long prospective cohort, including all patients admitted to a university hospital icu with moderate to severe traumatic brain injury (tbi), defined as a glasgow coma scale below twelve (gcs < ). blood samples for basal hormone values of thyroid-stimulating hormone (tsh) and free thyroxine (ft ) were obtained on days , , and . tsh serum concentrations were considered normal at > . mu/l; ft at > pmol/l. a thyrotropic insufficiency was defined as low ft and low tsh plasma levels. all patients were screened with a brain mri. patients were also monitored for neurological deterioration, including cognitive decline, convulsive seizures, increase in cerebral edema and brain herniation that were simultaneous to the diagnosis. results: during our study period's, trauma patients were admitted to our icu and met the inclusion criteria. on admission, our patients had a mean age at . ± , a mean injury severity score (iss) at ± , a mean abbreviated injury severity (ais) of the head at . ± . and a mean gcs at ± . of the patients a thyrotropic insufficiency was diagnosed in patients ( %) during the first days. the median delay to thyrotropic insufficiency diagnosis was days. in three of ( %), the thyrotropic insufficiency was nonrecovering during the patient's icu stay and was transient for the rest. none of the patients with acute thyrotropic insufficiency had direct hypothalamic or pituitary lesions on the brain mri. factors associated to the occurrence of acute thyrotropic insufficiency were: the ais of the head ( . ± . vs. ± . , p = . ), cerebral contusions ( % vs. %, p = . ), subarachnoid haemorrhage ( % vs. %, p = . ) and subdural haematoma ( % vs. %, p = . ). thyrotropic insufficiency was associated to neurological deterioration (p = . ) on the day of diagnosis but did not affect icu mortality ( % vs. %, p = . ). in this study, low pituitary-thyrotropic axis hormone levels were found in the acute phase of tbi and were associated to neurological deterioration but with no perceived effect on icu mortality. compliance with ethics regulations: yes. rationale: acute diabetes insipidus following head injury and its effect on patients outcome have not been sufficiently evaluated in large prospective studies. the aim of this study was to determine the incidence of acute cdi, delay of onset predictive factors and its impact on tbi patients. we conducted a prospective cohort, including all patients admitted to icu with moderate to severe tbi, defined as a glasgow coma scale (gcs) below twelve. for each tbi patient plasma sodium was measured daily, and if abnormally high, urine specific gravity and osmolality were measured. cdi was diagnosed using the seckl and dunger criteria. acute cdi was defined as cdi diagnosed in the first week following injury. all patients were screened with a brain mri. results: during our study's period, trauma patients were admitted to our icu, presented with moderate to severe tbi and were included. on admission, our patients had a mean age at . ± , a mean injury severity score (iss) at ± , a mean abbreviated injury severity (ais) of the head at . ± . and a mean gcs at ± . twenty-three percents ( patients) of the patients developed hypernatremia and % ( patients) were diagnosed with acute cdi. in of ( %), the cdi was nonrecovering. the median delay to develop transient cdi was h and for non-recoviring cdi was h (p = . ). none of the patients with acute cdi had direct hypothalamic or pituitary lesions. factors associated to the occurrence of acute cdi were: younger age ( ± vs ± , p = . ), neuro-surgery ( % vs. %, p < . ), hemorrhagic shock ( % vs. %), p < . ), cerebral edema ( % vs. %), p < . ), and fractures to the base of the skull ( % vs. %, p = . ). patients who developed cdi had a significantly higher mortality than those who did not ( of ( %) vs. of ( %), p < . ). there were no difference in terms of mortality between non-recovering and transient cdi ( % vs. %, p = . ), similarly the onset of cdi did not affect mortality ( h vs. h, p = . ). patients with acute cdi had poor glasgow outcome scale ( ± . vs. . ± . , p < . ) and longer icu los ( ± vs. ± , p = . ). conclusion: acute cdi is associated with higher mortality and poor outcome. therefore it is essential to diagnose and treat it promptly and correctly. compliance with ethics regulations: yes. acute glucocorticoid deficiency following traumatic brain injury mariem dlela, rania ammar zayani, abir bouattour, najeh baccouche, mounir bouaziz habib bourguiba hospital, sfax, tunisia correspondence: mariem dlela (mariem @gmail.com) ann. intensive care , (suppl ):p- rationale: published data demonstrates that long-term hypopituitarism could be common after traumatic brain injury (tbi).however, few studies focused on radiological, clinical, and repetitive endocrine assessment in the acute phase. the aim of the study was to evaluate the early changes in the adrenal axis following (tbi) and to evaluate whether hormone changes affect patient's outcome. we conducted a prospective study, including all patients admitted to a university hospital icu with moderate to severe traumatic brain injury (tbi), defined as a glasgow coma scale below twelve (gcs < ). each patient underwent sequential measurement of plasma cortisol (pc) on days , , and after tbi. we defined adrenal insufficiency as pc less than ng/ml. patients who received glucocorticosteroid therapy were excluded. outcome was measured by incidence of death, and glasgow outcome scale (gos) on day thirty. souhila sadat, dalila zeghdoud, dalila bougdal, kamel guenane ehs salim zemirli, alger, algeria correspondence: souhila sadat (sadatsouhila@hotmail.fr) ann. intensive care , (suppl ):p- rationale: the renewed interest in the pathophysiology of severe traumatic brain injury (tcg), allowed the understanding of the pathophysiological mechanisms leading to neuronal death.the non-invasive, easy, patient-based technical dtc allows evaluation of cerebral blood flow. purpose of the study: to determine the contribution of transcranial doppler (dtp) in the prevention of post-traumatic ischemia. patients and methods: a monocentric, observational, prospective study over a period of years, including tcg in the monitoring of cerebral blood flow (dsc) was provided by the dtc. we collected the following data: age, gender, lesion mechanism, lesion association, glasgow score at admission, time to perform the initial scan, time to perform the initial doppler, various abnormalities found at the initial dtp, the analysis of the level of map according to each situation of cerebral blood flow, the proposed therapies, the time to obtain a correct dtc. ( %), the statistical analysis showed no difference between the delay in setting up a hypohemia and the presence of a correct cerebral blood flow (p = . ), the statistical analysis of the map in the dtc group hypohemia compared to the correct dtc group objectified the absence significant difference between the two groups. the realization of dtp allowed therapeutic prioritization, the introduction of norepinephrine was in % of cases, osmotherapy in % of cases, optimization of sedation in . % of cases, the introduction of penthotal in . % of cases and the completion of decompressive in . % of cases. statistical analysis of mortality showed a significant difference in mortality (p = . ) in the hypohemic dtc group compared with the correct doppler . conclusion: ttc is an essential monitoring tool of cerebral hemodynamics, which may in prove the neurologic outiome of tcg. compliance with ethics regulations: yes. rationale: hyponatremia is a frequent electrolyte disturbance in hospitalized patients. it is particularly common in brain-injured patients with significantly elevated morbidity and mortality. the aim was to study the prevalence of hyponatremia in the acute phase of post-traumatic cerebral aggression, its degree of severity, its predictive factors as well as its prognostic impact in the population of post-traumatic brain injury. patients and methods: this is a retrospective study, carried out over a period of years about all traumatized head patients who developed hyponatremia during the first h of their stay. the descriptive part treated all patients who developed hyponatremia by detailing its different stages of severity.the analytical part treated the patients who developed a hypo-osmolar hyponatremia with a threshold of mmol/l retained to define the severity. during the study period, the incidence of hyponatremia in head trauma patients was . %. the occurrence of hyponatremia was associated only with the occurrence of early seizures (p = . ).severe hyponatraemia was associated with paroxysmal occurrence (p = . ), mass effect (p = . ), and hemostasis disorders. the multivariate study revealed that severe hyponatremia was associated with the glasgow score (p < . ) and pupillary changes (p = . ). on the other hand, it is the initial variation in serum sodium that was associated with both the severity of the initial neurological examination; glasgow (p < . ), saps (p = . ), pts (p = . ) and prism scores (p = . ), haemodynamic instability (p = . ) and neurovegetative disorders (p = . ). lesional features have also been found.regarding the prognosis, the occurrence of initial hyponatremia had a protective effect: a more favorable gos score p = . and a lower mortality (p = . ). a poor neurologic prognosis as well as a high mortality were associated with the most severe hyponatraemia and particularly with the initial variation of the sodium level (p = . ;). the mortality was . %. it was also particularly related to the initial change in sodium levels (p < . , . ). we concluded that there is no association between post traumatic early hyponatremia and the severity of the initial clinical presentation. however, the depth of hyponatremia and especially the initial change in sodium levels have been associated with more severe clinical pictures and a more limited prognosis. compliance with ethics regulations: yes. rationale: post-traumatic epilepsy (pte) is one of the complications described in the aftermath of headtrauma. its incidence is variable in the literature because of its clinical polymorphism. objectives of the study was to analyze the epidemiological profile (clinico-biological, radiological, therapeutic and evolutionary) of the patients having presented pte and to determine the risk factors for this pathology by comparing them with the rest of the traumatized brain patients. patients and methods: our study was retrospective. it was conducted in the intensive care unit (icu) of our university hospital between and . were included in our study all patients admitted to the service with brain injury and a glycaemia above mmol/l during the first h post-trauma. results: the incidence of pte was . %. ( among ) the average age was . ± . years. the sex ratio was . . the average of gcs was . ± . . three ( . %) patients had initial motor impairment. seizures were observed in ( . %) patients during the first h of hospitalization. the mean delay of occurrence of pte was ± . months. pte was diagnosed before the end of the first post-traumatic year in patients ( % of cases). the most commonly observed brain lesions were cortical brain contusions ( rationale: electrolytic disorders are common in neuro-resuscitation, especially dysnatremias and dyskalemias. hyponatremias are the most frequent, including the main etiologies: the syndrome of inappropriate secretion of antidiuretic hormone (siadh) and the "cerebral salt wasting" syndrome (csw). diabetes insipude of central origin secondary to a lack of dha secretion is the second most common disorder. patients and methods: it is a prospective study, analysing all the brains injured admitted to the a intensive care unit of chu hassan in fez, morocco. study spread over a -month period from / / to / / . the objective of the study is to detect the most frequent hydro-electrolytic disorders and to evaluate the therapeutic effectiveness of the service protocols. results: all these brains injured have caused he disorders over a period of time varying between d and d : * cases of hyponatremia ( %)/ cases of hypernatremia ( %), * cases of hypokaliemia ( %)/ cases of hyperkaliemia ( %), * cases of hyperchloremia, or %/ cases of hypochloremia ( %). * cases of diabetes insipidus, or . %. * cases without he disorder ( . %). the treatment for these disorders was: *for hypona; it reached mmol/l, initially corrected by a -hour water restriction, followed by an increase in the basic ration and furosemide boluses according to the ecv, even sodium loads for a single case of salt loss syndrome, while the main etiology remains the siadh. *for hyperna, it has reached mmol/l, evaluated by the extracellular volume, corrected by enteral tap water after calculation of the hydric deficit. if hperna is associated with polyuria greater than cc/kg/h; we speak of: *insipude diabetes, with polyuria up to cc/kg/h, compensated with potassium-containing solutions and blood ionogram monitored every h. desmopressin was used in titration, by bolus of . µg, with a diuresis objective between and . ml/kg/h. *for hypokalemia, up to . g/dl, observed mainly in the acute phase of brain aggression, corrected by increase in br for a k between . and g/l, and by potassium loads if k below . g/l. the evolution: deaths or . % ( cases of uncorrected diabetes insipidus), the restriction of disorders were corrected. conclusion: a knowledge of the hydroelectrolytic disorders encountered in this context is essential, as well as the implementation of a diagnostic and therapeutic protocol, which will reduce the time required to correct these disorders. compliance with ethics regulations: yes. . ] u/h). however, workload was increased under star ( vs. measurements per day), as expected from measurement interval difference between star ( -hourly) and the sp ( -hourly). conclusion: this unique patient-specific risk-based dosing approach gc framework was successful in controlling all patients safely and effectively. these preliminary results are encouraging and show gc can be achieved safely and effectively at lower target bands. in turns, these improved gc outcomes could improve patient outcomes. compliance with ethics regulations: yes. rationale: although its incidence has declined in recent years, gastric cancer remains common worldwide and is the leading cause of gastrectomy. his treatment is mainly surgical, but his prognosis remains poor. many studies on survival and prognostic factors have been carried out in foreign series. patients and methods: this is a retrospective study covering a period of three years from january to december interesting patients who had a gastrectomy and hospitalized in emergency resuscitation department surgical uhc ibnou rochd from casablanca. the statistical analysis of the different clinical, paraclinical and therapeutic data was carried out thanks to an exploitation sheet. rationale: gram-negative bloodstream infections (gnbsi) require timely appropriate antimicrobial therapy in intensive care units (icu) patients. conventional techniques usually take - h for antimicrobial susceptibility testing (ast). innovative approaches (accelerate pheno ™ system) provide pathogen identification in ~ h and ast including minimal inhibitory concentrations (mics) in ~ h. we report, in icu patients with gnbsi, results of implementation of the accelerate pheno ™ in our laboratory. we prospectively screened all gnbsi episodes reported in adult icu patients between september and september . to allow integration into the laboratory workflow, the accelerate pheno ™ was run on blood bottles positive before am (day ), in parallel with routine procedures: maldi-tof identification after short incubation on solid media (day ), β lacta (bio-rad ® ) test (day ) and disk diffusion method for ast (day+ ). for each episode, antimicrobial regimen was reassessed by a multidisciplinary team of bacteriologists, infectious diseases and icu physicians by the end of day . we measured: (i) concordance of accelerate pheno ™ results with conventional techniques, (ii) number of antibiotic adaptations on day and (iii) number of patients within the therapeutic range (free fraction over x mic and below concentration at risk of adverse events), based on real-time measurement of beta-lactams concentrations. results: of patients reported with gnbsi over the study period, were included. mean age was of ± . years, / were males. main sources of gnbsi were pulmonary (n = ) and digestive (n = ). bacterial identification of the accelerate pheno ™ was concordant with standard techniques in ( %): enterobacteriacae (n = ), pseudomonas aeruginosa (n = ). overall categorical agreement for ast was of % ( errors including very major errors). by the end of day , the antibiotic regimen was de-escalated in ( %) patients, which was appropriate in ( %). in cases, de-escalation was possible, but not fulfilled by icu physicians. twenty patients had beta-lactams concentrations measurements: were in the therapeutic range, below and over. conclusion: accelerate pheno ™ provided rapid and accurate results for most microorganisms isolated in blood cultures of icu patients with gnbsi. however, in a laboratory with routine maldi-tof early identification and β lacta test performed on day , the impact on early adaptation of the antibiotic regimen was evident in around patient over . compliance with ethics regulations: not applicable. jean-luc baudel , jacques tankovic , redouane dahoumane , jean-remy lavillegrand , razach abdallah , geoffroy hariri , naike bige , hafid ait-oufella , nicolas veziris , eric maury , bertrand guidet service bactériologie, hôpital saint-antoine, paris, france; service réanimation médicale, hôpital saint-antoine, paris, france correspondence: jean-luc baudel (jean-luc.baudel@aphp.fr) ann. intensive care , (suppl ):p- rationale: evaluation of the accurateness of the accelerate phenotest bc kit for rapid analysis ( . h for microorganism identification and additional hours for antibiotic susceptibility testing) of positive blood cultures from icu and hematology patients. patients and methods: from february to august , we included patients from the icu and hematology units with positive blood cultures. the following informations were collected : gender, age, duration of prior antibiotherapy, source of the infection, results obtained by conventional microbiological methods and by phenotest (data obtained and time to obtention of results). informed consent was obtained from all patients. results: blood cultures were analyzed in patients (m/f ratio . , age . ±, from the icu and from hematology). % of the patients were receiving antibiotics at the time of blood culture collection (mean duration : . days). the source of infection was unknown in % of cases, urinary in %, catheter-related in %, ascites in %, pneumonia in %. in cases ( %), there was a perfect match between phenotest and conventional results (identification and antibiotic susceptibility testing). in cases ( %), the bacterium responsible was not present in the phenotest panel. in cases ( %), phenotest identification was correct, but some discrepancies were observed regarding antibiogram. in cases ( %) phenotest identification was again correct but no antibiogram was available. in cases ( %), where two bacteria were present, phenotest could not identify one of them. in cases, phenotest did not provide bacterial identification because too few bacteria were present in the blood culture bottle. conclusion: the phenotest panel covered % of the bacteria implicated in this study. when the bacterium responsible was present in the panel, the results given by the phenotest correlated in % of cases with those of conventional methods. some rare discrepancies were observed regarding antibiotic susceptibility testing that have to be analyzed further. in the remaining % of cases, where too few bacteria or two different bacteria were present in the blood culture bottle, technical limitations did not permit to correctly identify microorganism(s) present or to obtain an antibiogram. compliance with ethics regulations: yes. mélanie fromentin, antoine bridier-nahmias, constance vuillard, jean-damien ricard, damien roux inserm umr iame infection antimicrobials modelling evolution, paris, france correspondence: mélanie fromentin (mel.fromentin@wanadoo.fr) ann. intensive care , (suppl ):p- rationale: studying human lower respiratory tract microbiota by using ngs (new generation sequencing) method is complex because of many unexpected biases due to dna extraction and amplification procedures. lung microbiota evolution under mechanical ventilation evolution may be highly informative to evaluate the actual risk of vap (ventilator-associated pneumonia) development. before starting a large study on the lung microbiome of ventilated icu patients, a methodological study was mandatory. patients and methods: five control and three vap patients were selected. endotrachealaspirate (eta) and oropharyngeal swab (os) were collected at icu admission for control patients and, days before and on the day of vap diagnosis for vap patients. after automated extraction of total dna, hypervariable region v of the s rdna genes was amplified with two different pairs of primers f- r: oligonucleotides from the earth microbiome project (earth primer pair) and from the gut microbiome project (gut primer pair), followed by sequencing on illumina miseq plateform. after bioinformatics analysis with mothur ® software, we compared the performance of ngs alongsideconventional bacterial culture. differences in alpha diversity (microbial diversity in a sample), expressed as the shannon index, across respiratory tract site (upper or lower) and across time (before and at vap time) has been investigated. a positive control (pc), rationale: colistin is used as a last-line treatment to combat multidrug-resistant (mdr) gram-negative bacilli (gnb). worryingly, colistin resistance in klebsiella pneumoniae, pseudomonas aeruginosa and acinetobacter baumannii is increasingly reported worldwide. we hereby report the prevalence of colistin resistance among gnb isolated from burn patients in tunisia. the study was carried out on strains of gnb isolated from microbiological samples of burn patients hospitalized in the intensive care unit between october and december . identification was performed by conventional methods. antimicrobial susceptibility was tested by disk diffusion method and the results were interpreted according to ca-sfm guidelines. minimum inhibitory concentration (mic) of colistin was determined using the eucast broth micro-dilution method (umic, biocentric ® ) results: pseudomonas aeruginosa was the most frequently isolated bacteria ( strains), followed by acinetobacter baumannii ( strains) and klebsiella pneumoniae ( strains). the most common sites of isolation were blood cultures ( %), catheters ( %) and skin samples ( %). most of p. aeruginosa isolates were multidrug-resistant with high levels of resistance to imipenem ( . %), ceftazidime ( %) and ciprofloxacin ( . %). however, all of them were susceptible to colistin. in fact, mics of colistin against all p.aeruginosa isolates were less than or equal to . mg/l. a. baumannii strains had high resistance rates to beta-lactams : % to ceftazidime and % to imipenem. only one strain was resistant to colistin with a mic equal to mg/l. all k. pneumoniae isolates were resistant to extended-spectrum cephalosporins. one third of these strains were resistant to imipenem and more than half ( . %) were resistant to amikacin. two strains were resistant to colistin with high mics (> mg/l). both were carbapenemase-producers, carrying oxa- and ndm carbapenemase encoding genes. conclusion: these data suggest that colistin-resistant or pan-drug resistant gnb clinical isolates are still relatively rare. however, they have important global public health implications because of the therapeutic problems they present, especially for vulnerable populations such as severely burned patients. hence the need to test colistin regularly in the laboratory and to set up a monitoring program for mdr pathogens. compliance with ethics regulations: yes. rationale: descending necrotizing mediastinitis (dnm) are medicosurgical emergencies whose forecast is closely related to the precocity of the therapeutic assumption. the purpose of our work is to profile these patients as well as the therapeutic and evolutionary aspects. patients and methods: retrospective study over years in the intensive care unit of the hospital august. all patients with dnm on cervicofacial cellulitis were included. results: cases were collected, % of cellulitis, incidence of . patients / year. average age , sex ratio of . . smoking, chronic alcoholism and diabetes are the most common antecedents. the favoring factors were: (poor dental conditions: % of cases, non steroidien anti-inflammatory drugs: %, diabetes: %). in % of cases the front door was dental. average time taken to take care of days. c-reactive protein and procalcitonin were positive in all patients. in % the chest x-ray was normal. all patients received tri-antibiotic therapy. intubation were difficult in all patients, we used nasofibroscope in % of cases and a rescue tracheotomy in one patient. only one patient had a cervico-thoracic surgical approach; for all the others she was cervical alone. streptococcus was the most isolated germ. the complications were (septic shock: %, ards: %). the average hospital stay was days with a mortality rate of %. conclusion: dnms are poorly prognostic. the best treatment remains prevention by better management of dental abscesses and tonsillar phlegmons. rationale: the initial, empirical antibiotic therapy of ventilator-associated pneumonia (vap) is often based on timing of its occurrence in relation to the onset of mechanical ventilation. this is due to reported differences between causal pathogens associated with early-onset (e-vap < - days of mechanical ventilation) compared to late-onset vap (l-vap ≥ - days of mv). e-vap is most often reported to be due to antibiotic-sensitive pathogens while l-vap is frequently attributed to antibiotic-resistant pathogens. however, there is emerging evidence that the isolated microorganisms may be similar regardless of onset time. the aim of our study was to compare the clinical outcomes of critically ill patients developing e-vap and l-vap and to compare the causative pathogens of the two groups. patients and methods: all the patients with the diagnosis of vap admitted between january and december were retrospectively included. vap was suspected on the basis of clinical and chest x-ray findings. the identification of the causative organisms was performed with endotracheal aspirate (eta) cultures. results: ninety patients developed vap. e-vap was observed in patients ( , %), whereas patients ( , %) developed l-vap. among patients with early-onset vap, % received antibiotics prior to the development of pneumonia, compared to % with late-onset vap (p = . ). otherwise, no differences (sociodemographic factors, antecedents, severity score, length of stay, length of mv) between the two groups were observed. the most common pathogens associated with e-vap were enterobacter species ( . %), pseudomonas aeruginosa ( . %) and oxacillin-resistant staphylococcus aureus (orsa , %). enterobacter species ( . %), acinetobacter baumannii ( . %) and pseudomonas aeruginosa ( %) were the most common pathogens associated with l-vap. no difference was noted in the contribution of multidrug resistant bacteria mdr ( % vs. %). hospital mortality was significantly greater for patients with l-vap caused by mdr ( %) compared to patients with e-vap ( %) (p = . ). conclusion: this classification is no longer helpful for empirical antibiotic therapy, since both early-onset and late-onset vap were caused by mdr bacteria. this justifies the need of intensive care unit-specific knowledge of causal agents associated with vap to reduce the rate of administration of inadequate antimicrobial therapy. compliance with ethicsregulations: yes.