key: cord-0036014-sm937muh
authors: Argent, Andrew C.; Kissoon, Niranjan “Tex”
title: Mechanical Ventilation in Infection, Sepsis and Organ Failure
date: 2013-10-08
journal: Pediatric and Neonatal Mechanical Ventilation
DOI: 10.1007/978-3-642-01219-8_54
sha: f57cdefffc3099f3b849b71e5eb13111d987610b
doc_id: 36014
cord_uid: sm937muh

Each day thousands of children across the world die as a result of infection. Sepsis, severe sepsis and septic shock represent a continuum of increasing severity for which present definitions are not wholly satisfactory (Levy et al. 2003; Brilli and Goldstein 2005). The term sepsis refers to the presence of an infection caused by a microbe that invades tissue, fluid or a body cavity that is normally sterile, plus the presence of clinical and/or laboratory evidence of the systemic inflammatory response syndrome (SIRS, temperature or leucocyte abnormalities and abnormal vital signs) (Goldstein et al. 2005). When sepsis is complicated by multi-organ failure, it is regarded as severe, while septic shock is diagnosed when sepsis coexists with a state of acute circulatory failure (Levy et al. 2003).

Each day thousands of children across the world die as a result of infection. Sepsis, severe sepsis and septic shock represent a continuum of increasing severity for which present defi nitions are not wholly satisfactory (Levy et al. 2003 ; Brilli and Goldstein 2005 ) . The term sepsis refers to the presence of an infection caused by a microbe that invades tissue, fl uid or a body cavity that is normally sterile, plus the presence of clinical and/or laboratory evidence of the systemic infl ammatory response syndrome (SIRS, temperature or leucocyte abnormalities and abnormal vital signs) . When sepsis is complicated by multi-organ failure, it is regarded as severe, while septic shock is diagnosed when sepsis coexists with a state of acute circulatory failure (Levy et al. 2003 ) .

Sepsis may be related to a wide variety of different microorganisms (including bacteria, viruses, protozoa, rickettsiae and fungi) with many different toxins and pathogenetic mechanisms. In addition, the clinical features of infection in a patient may vary due to a variety of factors including the genetic predisposition (Opal 2007 ) ; infective dose, route of infection and virulence factors of the particularly organism; possible co-infections; and underlying illness, nutritional status, medication; and the organs affected by the infection (and responses) (Opal 2005 ) .

Thus septic patients who require ventilation make up a very broad spectrum of contexts and specifi c situations. The indications for and the goals of ventilation may therefore vary considerably in patients (Table 54 .1 ).

• Consider an approach to ventilation in patients with sepsis of all kinds. • Discuss some of the possible modes of ventilatory support, with particular attention to their potential use in patients with sepsis or organ failure. • Consider anaesthesia for initiation of invasive ventilation in patients with sepsis. • Defi ne the goals of ventilation in patients with severe sepsis or organ failure. • Review the cardiovascular implications of ventilatory support in patients with sepsis. • Consider processes to minimize lung damage during ventilation. • Consider specifi c infections and some of the implications for ventilation. • Briefl y address issues of infection control. (SIRS) The presence of at least two of the following four criteria, one of which must be abnormal temperature or leucocyte count Core temperature of >38.5 °C or <36 °C Tachycardia, defi ned as a mean heart rate >2 SD above normal for age in the absence of external stimulus, chronic drugs or painful stimuli or otherwise unexplained persistent elevation over a 0.5-to 4-h time period, OR, for children <1 year old, bradycardia, defi ned as a mean heart rate <10th percentile for age in the absence of external vagal stimulus, β-blocker drugs or congenital heart disease or otherwise unexplained persistent depression over a 0.5-h time period Mean respiratory rate >2 SD above normal for age or mechanical ventilation for an acute process not related to underlying neuromuscular disease or general anaesthesia Leucocyte count elevated or depressed for age (not secondary to chemotherapy-induced leucopenia) or >10 % immature neutrophils 

Strategies for assisting ventilation include endotracheal intubation and positive pressure ventilation and recently several other modes including noninvasive techniques. Ventilatory support using high-fl ow humidifi ed nasal oxygen has been introduced into neonatal practice for respiratory support. There are limited reports of its use in older children with respiratory distress (Spentzas et al. 2009 ; McGinley et al. 2009 ). There are a number of commercial systems available. There is considerable variability in the pressures and fl ows delivered to infants with these systems (Dani et al. 2009 ; Lampland et al. 2009 ), and it is suggested that pressure limitation devices should be incorporated (Lampland et al. 2009 ). More research is required before these can be recommended for respiratory support in children (Randolph 2009 ) with acute respiratory distress.

Noninvasive ventilation has been attempted in children with acute respiratory failure due to a wide variety of conditions (Teague 2005 ) including neuromuscular conditions (Katz et al. 2004 ; Reddy et al. 2004 ; Hartmann et al. 1994 ) , asthma (Haggenmacher et al. 2005 ; Ram et al. 2005 ) as well as acute respiratory failure due to infections (Prado et al. 2005 ; Piastra et al. 2004 ; Fortenberry et al. 1995 ) .

After an initial report of nCPAP in an infant with apnoea related to RSV infection (McNamara and Sullivan 1997 ), Thia et al. ( 2008 ) demonstrated that nCPAP administered to infants with bronchiolitis and hypercapnia was associated with signifi cant improvement.

A report on 14 patients from Chile (Prado et al. 2005 ) showed that nCPAP or BiPAP administered via nasal mask in acute respiratory failure due to infection was associated with signifi cant improvement and that most children did not need invasive ventilation.

A recent Cochrane review of negative pressure ventilation in acute respiratory failure (Shah et al. 2005 ) concluded that there was not enough evidence available to make a recommendation as to its clinical applicability.

Thus it may be possible to use conventional or noninvasive (including nCPAP, BiPAP and mask) ventilation in children with acute respiratory failure related to infection. Unfortunately fi rm recommendations cannot be made until challenges in terms of masks (including fi t), indications and techniques are elucidated (Teague 2005 ; Loh et al. 2007 ) and proposed predictors of success (Bernet et al. 2005 ) 

Anaesthesia for endotracheal intubation for conventional ventilation is essential, but there is considerable controversy regarding the optimal agents for anaesthesia in acute sepsis (Zelicof-Paul et al. 2005 ) . Selection of appropriate agents will depend on experience and training.

Etomidate has been used in a number of studies, but there remains considerably concern regarding possible adrenal suppression following its use in sepsis (Zed et al. 2006 ; Zuckerbraun et al. 2006 ) . It does however create favourable conditions for intubation (Zelicof-Paul et al. 2005 ) and is less likely to cause hypotension than agents such as midazolam (Choi et al. 2004 ).

Ketamine has been used extensively in many settings with a very low complication rate (Melendez and Bachur 2009 ; Jankiewicz and Nowakowski 1991 ) and is an agent of choice in many emergencies, while propofol and thiopentone have been used with some success.

There is a theoretical benefi t for giving atropine when manipulating the airway of infants under 1 year of age due to their disproportionate predominance in vagal tone coupled with a relatively greater dependency on HR for cardiac output (Rothrock and Pagane 2005 ) . However recent evidence suggests that it may be unnecessary (Brown et al. 2008 ) when ketamine alone is used for anaesthesia. Most bradycardias are due to hypoxia or are a transient vagally mediated refl ex response that resolves spontaneously. In special circumstances, such as infants less than 1 year of age, atropine is still considered an option by some practitioners especially prior to a second or repeat dose of succinylcholine.

The choice of agent for paralysis in intubation under emergency conditions remains controversial. Recent reviews of the adult literature have concluded that there is no benefi t to rocuronium and that succinylcholine remains the safest agent (Perry et al. 2008 ). In the 1990s reviews of the use of succinylcholine vs. rocuronium concluded that succinylcholine remained the recommended choice although this was essentially a matter of personal preference (Robinson et al. 1996 ; Weir 1997 ) . There have been concerns about the possibility of hyperkalaemic cardiac arrest in the setting of undiagnosed neuromuscular disease. A recent paediatric review (Ching and Baum 2009 ) has concluded that rocuronium may be a safer agent for use in emergency intubation in children.

A signifi cant concern that has been raised recently (Kendrick et al. 2009 ) is that the duration of action of agents such as rocuronium or atracurium is signifi cantly longer than that of etomidate. Thus patients who are intubated using the combinations of etomidate and rocuronium or atracurium should receive sedation after intubation to avoid the possibility of awareness while paralysed.

Mechanical ventilation in respiratory failure has been one of the core functions of intensive care since the earliest days of the speciality (Grenvik and Pinsky 2009 ). The goals of mechanical ventilation have primarily been focused on the maintenance of acceptable blood gases in patients with failure of the respiratory system, but there is also a considerable body of literature related to cardiopulmonary interactions and the effect of mechanical ventilation on cardiovascular function (Bronicki and Anas 2009 ) .

Essentially the goals of ventilation in sepsis and organ failure could be summarized as: Maintenance of blood gas values that are appropriate to the overall management of the patient (taking into account the effects of sepsis of all organ systems) Optimization of cardiovascular function Minimizing damage to the lungs and the respiratory system Minimizing deleterious effects on other organ systems

The priorities of ventilation in sepsis, from the immediate resuscitation at the time of presentation through the recovery phases of the illness, may differ as the physiology changes. Thus acceptable goals will depend on the stage of the illness.

It has been generally accepted that mechanical ventilation in patients with respiratory disease should not always be aimed at the maintenance of normal blood gas values, and recent reviews refer to both permissive hypoxaemia (Cheifetz and Hamel 2006 ) and hypercapnia (Hickling 2002 ) and even to therapeutic hypercapnia (Laffey et al. 2000 (Laffey et al. , 2004a Kavanagh and Laffey 2006 ) .

Tissue oxygen delivery in sepsis may be complex and is affected by the interrelationship of multiple factors (Table 54 .2 ). Optimal oxygen delivery globally or to specifi c organs is important (particularly in the setting of organ failure).

On the other hand, it is possible that high oxygen concentrations may be problematic, particularly if there are defi ciencies in antioxidant defences (Salvemini and Cuzzocrea 2002 ) which may occur in several settings, including malnutrition.

Deleterious effects of high oxygen concentrations on the lung have been well documented for many years (Pagano and Barazzone-Argiroffo 2003 ) .

There is considerable animal evidence that high inspired oxygen concentrations in combination with mechanical ventilation may be related to increased pulmonary infl ammation and lung damage (Sinclair et al. 2004 ; Altemeier and Sinclair 2007 ) . Sinclair et al. also showed that in rabbit model ventilation with moderate tidal volumes using 50 % oxygen (previously regarded as relatively safe) was associated with signifi cant lung damage as compared to ventilation with room air (Sinclair et al. 2004 ) . Experience in neonatology (Ehlert et al. 2006 ) has also highlighted the deleterious effects of high tidal volumes and hyperoxia.

Apart from effects on the lung, ventilation with high oxygen concentrations adversely affects alveolar macrophage and other immune functions (Baleeiro et al. 2003 (Baleeiro et al. , 2006 and increases mortality from Legionella pneumophila (Tateda et al. 2003 ) in animal models.

Studies on the effect of hyperoxia on surgical site infections and outcomes following major surgery have yielded confl icting results (Pryor et al. 2004 ; Greif et al. 2000 ) .

The effects of high oxygen concentrations on tissue in the setting of sepsis are controversial with studies reporting that high oxygen concentrations during resuscitation from haemorrhagic shock are associated with signifi cant benefi ts (Brod et al. 2006 ) , while other studies report opposite effects. These reports may be germane to patients with sepsis and multi-organ dysfunction which is associated with high oxidative stress (Alonso de Vega et al. 2000 Vega et al. , 2002 Motoyama et al. 2003 ) .

However, the fi ndings are diffi cult to reconcile. In a model of porcine faecal peritonitis, ventilation with 100 % oxygen (PEEP of 12-15 cm H 2 O, tidal volumes of 8 ml/kg, long inspiratory Multiple components of microvascular dysfunction have been described in sepsis and may affect tissue oxygen delivery (Bateman et al. 2003 ) times) was associated with improved splanchnic and renal blood fl ow together with improved organ function and reduced apoptosis in both the liver and lung when instituted either at the time of early peritonitis (Barth et al. 2008 ) or after established shock (Hauser et al. 2009 ).

Thus it would appear that in the early phases of resuscitation and ventilation for sepsis, the benefi ts of high inspired oxygen concentrations may outweigh its side effects. However once resuscitation is well underway, the benefi ts of high FiO 2 may be outweighed by increased lung damage and potentiation of infl ammation throughout the body.

Permissive hypercarbia has been well recognized as a reasonable approach to lung protection in severe lung disease (Sevransky et al. 2004 ) and has been associated with improved outcomes in preterm neonates with respiratory failure (Mariani et al. 1999 ). In addition there is evidence that the acidosis related to hypercapnia may have lung protective effects (Laffey et al. 2000 (Laffey et al. , 2004b . More recently hypercarbic acidosis has been shown to have protective effects on the lung in experimental sepsis (Laffey et al. 2004a ; Ni Chonghaile et al. 2008 ; Chonghaile et al. 2008 ) and also other organs (Costello et al. 2009 ).

Therefore, in respiratory failure due to sepsis, lung protective strategies such as permissive hypercapnia may need to be balanced against the possible deleterious effects due to pathology in other organs (e.g. the brain in meningitis) (Tasker and Peters 1998 ) .

Although permissive hypercapnia has been accepted, there is little evidence published defi ning either upper levels of acceptable pCO 2 or limits of pH (Sevransky et al. 2004 ).

Haemodynamic instability is a common feature of severe sepsis in children . While adults are likely to have normal to high cardiac output with low systemic vascular resistance in septic shock, children are more likely to have low cardiac output with high systemic vascular resistance (Ceneviva et al. 1998 ; Carcillo et al. 2002 ) . The impact of mechanical ventilation on haemodynamics depends on the interaction of many factors (Luecke and Pelosi 2005 ) including lung and chest wall mechanics (O'Quin et al. 1985 ) and characteristics of ventricular function (whether there is right, left or biventricular failure) (Bronicki and Anas 2009 ) . Cardiopulmonary interactions are generally complex (Bronicki and Anas 2009 ), more so in the critically ill (Pinsky 1985 (Pinsky , 1990 (Pinsky , 1994 (Pinsky , 1997 (Pinsky , 2005 (Pinsky , 2007 Jellinek et al. 2000 ) , and may be affected by a wide variety of issues in sepsis. Ventilation may alter venous return in patient with sepsis. For instance, in sepsis cardiac output may be decreased because of venodilatation and reduced venous return as well as high right atrial pressures due to positive pressure ventilation (Bronicki and Anas 2009 ). The relationship between ventilator pressures and right atrial pressure depends on the interaction between respiratory efforts and ventilator pressures, lung resistance and compliance, chest and abdominal wall compliance and the characteristics of the pericardium and cardiac muscle (Kingma et al. 1987 ) . Generally lung compliance in children is relatively low, while chest wall compliance is high, with the result that ventilator pressures are poorly transmitted to the right atrium. This may however not be true in sepsis, where the chest wall may become very non-compliant as a result of oedema, infl ammation and raised intraabdominal pressure.

Ventilation may also affect both right and left ventricular outputs. Right ventricular output varies depending on pulmonary vascular tone and resistance which is highest at low and high lung volumes and lowest at functional residual capacity (Bronicki and Anas 2009 ; Jardin 1997 ; Jardin and Vieillard-Baron 2003 ) . Thus positive pressure ventilation in sepsis may reduce pulmonary vascular resistance (and impedance) and improve right ventricular function by optimizing FiO 2 , pH and lung volumes. However, over-distension of the alveoli may be associated with deterioration of right ventricular function.

Left ventricular afterload is also increased if negative intrathoracic pressures are generated during respiration (Bronicki and Anas 2009 ) , and thus positive pressure ventilation may substantially reduce left ventricular afterload of patients in respiratory distress who have been generating very low intrathoracic pressures (as may be seen in sepsis). This may in turn improve cardiac output.

However, the left and right ventricles do not function in isolation and ventricular interactions that may determine the effect of ventilation on cardiac output (Tyberg et al. 2000 ; Biondi et al. 1988 ) .

For instance, if respiratory distress and suboptimal cardiac output coexist, the respiratory muscles may consume a signifi cant proportion of cardiac output. Mechanical ventilation may thus contribute signifi cantly to an improvement in organ perfusion by reducing respiratory muscle activity (Aubier et al. 1981 ; Viires et al. 1983 ) .

If left ventricular dysfunction is present in the septic patient, positive pressure ventilation may be associated with signifi cant improvements in cardiac output (Bronicki and Anas 2009 ) , while positive pressure ventilation may substantially reduce cardiac output if the patient is hypovolaemic.

In patients with acute lung injury recruitment, manoeuvres have been used in an attempt to improve respiratory function. These manoeuvres have been associated with signifi cant decreases in cardiac output in both animal and human adult studies (Lim et al. 2004 ; Toth et al. 2007 ) .

Cardiac function in severe sepsis can therefore be profoundly affected adversely or positively by positive pressure ventilation. The exact effects will depend on the specifi c situation and may have to be established by careful consideration of the physiological state and sometimes a process of trial and error.

The optimal ventilatory pattern to minimize damage to the lungs will depend both on the disease and on the specifi c lung pathology. Although the interplay is complex, the presence of predisposing factors (such as haemorrhagic shock) may exacerbate lung injury from inadequate ventilation (Bouadma et al. 2007 ), while inadequate ventilation may also exacerbate the infl ammatory response to shock.

The presence of infection (or infl ammation) also increases the lung and global infl ammatory response to ventilation with high tidal volumes and low PEEP. Nahum et al. ( 1997 ) demonstrated in a dog model that injurious patterns of ventilation (low PEEP and high tidal volume) signifi cantly increased the translocation of bacteria from the lung into the circulation and the infl ammatory responses within the lung. Altemeier et al. showed in rabbits that ventilation with 10 ml/kg tidal volume had a synergistic effect, increasing lung injury, with the systemic administration of LPS . Bregeon et al. using a rabbit model showed that when E. coli lipopolysaccharide was administered intravenously, ventilation with zero PEEP and 10 ml/kg of tidal volume was associated with signifi cant deterioration in lung mechanics, hypoxaemia and histological damage. Both authors demonstrated that mechanical ventilation alone did not induce lung injury, but mechanical ventilation together with aspiration of LPS was associated with an augmented infl ammatory response and the development of ARDS changes (Altemeier et al. 2005 ) .

Similar fi ndings have been reported by others O'Mahony et al. 2006 ; Bem et al. 2009 ) using a variety of models of ventilation during sepsis.

Thus a consistent theme in much experimental work in sepsis, mechanical ventilation (particularly with tidal volumes of 10 ml/kg or more) and high FiO 2 is associated with exacerbation of infl ammatory responses both in the lung and throughout the body. There is little experimental data available on children, but it would seem reasonable to use "lung protective" strategies of ventilation in the setting of sepsis. There may also be a place for cautious use of "recruitment" followed by reduced pressure ventilation to minimize lung damage (Rimensberger et al. 1999 ) .

Another consideration is the very common presence of fever in patients with sepsis. In an experimental study of ventilator-induced lung injury in rabbits, Suzuki et al. ( 2004 ) demonstrated that lung damage using potentially injurious forms of ventilation was exacerbated by hyperthermia relative to hypothermia.

Severe sepsis is the most common cause of both ALI and ARDS in a population-based study of ALI and ARDS in the USA (Zimmerman et al. 2009 ). Pneumonia and sepsis were described as the main causes of ARDS in children in study from China (Yu et al. 2009 ). ARDS/ALI has also been described in patients with malaria (less frequently in children) (Taylor et al. 2006 ; Mohan et al. 2008 ) , dengue (Lum et al. 1995 ) , Aspergillus (Anaissie 2008 ), tuberculosis and a whole host of viral infections.

Many studies have highlighted the potential benefi ts of ventilation with lower tidal volumes in adults with ARDS (Amato et al. 1995 (Amato et al. , 1998  The Acute Respiratory Distress Syndrome Network 2000 ; Meade et al. 2008 ; Brochard et al. 1998 ) . Although there are fewer studies in the paediatric literature, the overwhelming weight of evidence is that paediatric mortality with ARDS has decreased substantially with lower tidal volume ventilation (Hanson and Flori 2006 ; Mehta and Arnold 2004 ; Albuali et al. 2007 ), higher PEEP levels and permissive hypercapnia. The importance of careful attention to ventilation is highlighted in a study of children in septic shock in which hand ventilation for greater than 6 h doubled mortality (Santhanam et al. 2008 ).

The specifi c effect of various modes of ventilation depends on the underlying lung pathology (Naik et al. 1998 ). Greenough ( 2009 ) has recently reported a wide spectrum of lung disease in RSV infection ranging from obstructive lung disease with air trapping through restrictive lung disease with pneumonitis (Table 54 .4 ). In response ventilatory support from CPAP through ECMO may be required in these children.

Tuberculosis may be responsible for a range of lung pathology in acute infection including ARDS (Agarwal et al. 2005a , b ; Malhotra et al. 2005 ) , expansile pneumonia (Goussard et al. 2004 ) and pneumonia (Goussard et al. 2008a ), bronchopleural and broncho-oesophageal fi stulae (Goussard et al. 2008b (Goussard et al. , 2007 Gie et al. 1998 ), laryngeal tuberculosis (du Plessis and Hussey 1987 ) and phrenic nerve damage related to mediastinal adenopathy (Goussard et al. 2009 ). Good outcomes can be achieved in children less than 6 months of age requiring ventilation for tuberculosis, but early diagnosis and therapy are essential (Goussard et al. 2008a ) .

A particular concern when ventilating children with tuberculosis is safety of staff and the need to identify family members with infectious tuberculosis as a potential source of nosocomial infection (Heyns et al. 2006 ; Schaaf et al. 2003 ) .

Pertussis as a cause of severe pneumonia requiring intubation and ventilation has been underdiagnosed in some settings (Greenberg et al. 2007 ). The lung pathology in fatal cases reveals severe pulmonary hypertension and high white cell counts both of which may limit blood fl ow to the lung and poses signifi cant challenges with ventilation (Table 54 .3 ) (Paddock et al. 2008 ).

There are many potential reasons for reduction in chest wall compliance in patients with sepsis (Table 54 .4 ). The decreased chest wall compliance may result increased pressures seen during ventilation even with modest tidal volumes, but may also limit the chances of lung damage. Complications in the pleural space such as pneumothorax and other air leaks seen with a number of organisms including Pneumocystis jirovecii , Staphylococcus aureus and Streptococcus pneumoniae (Sivit et al. 1995 ; Wong et al. 2000 ) may also decrease overall compliance and may pose challenges in ventilation.

Similarly, infections with organisms such as Staphylococcus aureus and Streptococcus pneumoniae have a higher incidence of empyema which may also decrease compliance of the chest (Li and Tancredi 2009 ; Soares et al. 2009 ; Langley et al. 2008 ) . Effective drainage of fl uid, air and pus collections is essential to effective ventilation and management of these children. Thickening and changes of chest wall characteristics related to the fl uid shifts and infl ammatory processes in sepsis Changes in muscle function and particularly in diaphragmatic function related to the infl ammatory processes Abdomen

Abdominal distension with raised intra-abdominal pressure Organomegaly related to processes such as acute or even chronic hepatic failure Cardiovascular concerns Deterioration in cardiac muscle function related to infl ammatory process Development of large intrathoracic pressure changes related to acidosis and increased respiratory effort. This may signifi cantly increase cardiac afterload Fluid overload related to fl uid resuscitation attempts Renal concerns Renal dysfunction is common in sepsis and may be associated with acidosis, electrolyte abnormalities and fl uid overload. All of these may have adverse effects on the lungs Hepatic concerns Large liver (and ascites) may compromise diaphragmatic function In the setting of chronic hepatic failure, there may be an increase in intrapulmonary shunting with associated hypoxaemia Musculoskeletal concerns Muscle weakness related to sepsis, organ failure or therapy

Mechanical ventilation of infected patients poses a risk to staff and other patients. Effective antibiotic therapy will usually render bacterial pathogens noninfective rapidly, but there are considerable concerns with viral pathogens and organisms such as tuberculosis.

Ventilator care of infected patients may be associated with nosocomial spread of infection via a variety of methods including aerosolization of organisms and contamination of ventilators, and considerable care must be implemented to prevent this risk.

Staff caring for patients with respiratory disease are also at risk of infection, particularly during procedures such as intubation or endotracheal suctioning. The experience from epidemics such as SARS suggests that health-care workers in the intensive care environment need substantial training in the use of self-protective strategies (Chia et al. 2005 ) , while organizations need to consider the processes for staff protection (Moore et al. 2005 ) , and ongoing research is required to assess the risk related to aerosolization of organisms and related issues (Yassi et al. 2005 ) .

A particular concern is patients with immune defi ciencies who may continue to shed pathogens a long time after the initial presentation (Arbiza et al. 2006 ).

It is generally accepted that sputum characteristics are altered in patients with infection.

Children are particularly at risk of airway obstruction from secretions as a result of the relatively small endotracheal airway utilized during endotracheal intubation and ventilation. Particular attention needs to be paid to the issues of adequate airway humidifi cation during ventilation although the literature on this topic is extremely limited (Branson 2007 ; Niel-Weise et al. 2007 ; Ricard et al. 2006 ) . Suctioning is required to maintain patency of endotracheal tubes but may be associated with many and varied adverse effects (Morrow and Argent 2008 ) . The recommendations for suctioning were recently reviewed (Morrow and Argent 2008 ) and include the following: no routine suctioning (except perhaps in patients on neuromuscular blockade), use appropriate size suction catheters (2X the internal diameter of the endotracheal tube (mm) will give the approximate size (FG) of the suction catheter to be used), use the minimum suction pressure required to remove secretions (with a maximum of 360 mmHg), do not use saline routinely, and limit the duration of any particular suctioning manoeuvre.

Sepsis in children is associated with a wide range of clinical syndromes and challenges. Appropriate ventilation in patients with sepsis requires a broad understanding of the effects of ventilation on the cardiovascular and respiratory systems, as well as local and global infl ammatory responses.

In addition, it is extremely important to ensure that nosocomial spread of infection is limited and that staff are protected from the possibility of acquiring infections from their patients. 

• Sepsis may be associated with a wide variety of problems in multiple organs. • Aims of ventilatory support will be related to the particular organs that are affected by sepsis. • Ventilatory support must be focused on providing appropriate blood gases for the particular patient context while causing the least possible damage to the lungs. • The effects of ventilatory support on the cardiovascular system are closely related to the specifi c pathophysiology in a particular patient. Cardiovascular responses to ventilation must be carefully monitored with appropriate adjustment of ventilation. • Infection control measures, to protect both the ventilated patient and the staff and other patients, are an essential component of ventilatory support. • Patients with sepsis may need special attention to the adequate clearance of secretions on ventilation, but this must be done with great care.

Experience with ARDS caused by tuberculosis in a respiratory intensive care unit

Noninvasive ventilation in ARDS caused by Mycobacterium tuberculosis: report of three cases and review of literature

Have changes in ventilation practice improved outcome in children with acute lung injury?

Plasma redox status relates to severity in critically ill patients

Oxidative stress in critically ill patients with systemic infl ammatory response syndrome

Hyperoxia in the intensive care unit: why more is not always better

Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin

Modulation of lipopolysaccharide-induced gene transcription and promotion of lung injury by mechanical ventilation

Benefi cial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation

Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome

A bad bug takes on a new role as a cause of ventilator-associated pneumonia

Genetic characterization of respiratory syncytial viruses isolated from consecutive acute respiratory infections in a HIV infected child

Respiratory muscle fatigue during cardiogenic shock

Sublethal hyperoxia impairs pulmonary innate immunity

GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress

Effects of ventilation with 100% oxygen during early hyperdynamic porcine fecal peritonitis

Bench-tobedside review: microvascular dysfunction in sepsis -hemodynamics, oxygen transport, and nitric oxide

Mechanical ventilation enhances lung infl ammation and caspase activity in a model of mouse pneumovirus infection

Predictive factors for the success of noninvasive mask ventilation in infants and children with acute respiratory failure

Effects of mechanical ventilation on right and left ventricular function

Mechanical ventilation and hemorrhagic shock-resuscitation interact to increase infl ammatory cytokine release in rats

Secretion management in the mechanically ventilated patient

Pediatric sepsis defi nitions: past, present, and future

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Adjunctive atropine is unnecessary during ketamine sedation in children

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Hemodynamic support in fl uid-refractory pediatric septic shock

Is permissive hypoxemia a benefi cial strategy for pediatric acute lung injury?

Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore

Newer agents for rapid sequence intubation: etomidate and rocuronium

Midazolam is more likely to cause hypotension than etomidate in emergency department rapid sequence intubation

Hypercapnic acidosis attenuates lung injury induced by established bacterial pneumonia

Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis

High fl ow nasal cannula therapy as respiratory support in the preterm infant

Mechanical ventilation induces infl ammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia

Laryngeal tuberculosis in childhood

Hyperoxia and tidal volume: independent and combined effects on neonatal pulmonary infl ammation

Management of pediatric acute hypoxemic respiratory insuffi ciency with bilevel positive pressure (BiPAP) nasal mask ventilation

Tuberculous broncho-esophageal fi stula in children: a description of two cases

International pediatric sepsis consensus conference: defi nitions for sepsis and organ dysfunction in pediatrics

Expansile pneumonia in children caused by Mycobacterium tuberculosis: clinical, radiological, and bronchoscopic appearances

Esophageal stent improves ventilation in a child with a broncho-esophageal fi stula caused by Mycobacterium tuberculosis

The outcome of infants younger than 6 months requiring ventilation for pneumonia caused by Mycobacterium tuberculosis

Fibrin glue closure of persistent bronchopleural fi stula following pneumonectomy for post-tuberculosis bronchiectasis

Phrenic nerve palsy in children associated with confi rmed intrathoracic tuberculosis: diagnosis and clinical course

Pertussis is under diagnosed in infants hospitalized with lower respiratory tract infection in the pediatric intensive care unit

Role of ventilation in RSV disease: CPAP, ventilation, HFO, ECMO

Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. Outcomes Research Group

Evolution of the intensive care unit as a clinical center and critical care medicine as a discipline

Non-invasive bi-level ventilation in paediatric status asthmaticus

Application of the acute respiratory distress syndrome network low-tidal volume strategy to pediatric acute lung injury

Negative extrathoracic pressure ventilation in central hypoventilation syndrome

Hemodynamic, metabolic, and organ function effects of pure oxygen ventilation during established fecal peritonitis-induced septic shock

Nosocomial transmission of Mycobacterium tuberculosis in kangaroo mother care units: a risk in tuberculosis-endemic areas

Ketamine and succinylcholine for emergency intubation of pediatric patients

The hemodynamic consequences of mechanical ventilation

Right ventricular function and positive pressure ventilation in clinical practice: from hemodynamic subsets to respirator settings

Right atrial pressure predicts hemodynamic response to apneic positive airway pressure

Outcome of non-invasive positive pressure ventilation in paediatric neuromuscular disease

Hypercapnia: permissive and therapeutic

Sedation after intubation using etomidate and a long-acting neuromuscular blocker

Left ventricular external constraint: relationship between pericardial, pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs

Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion

Hypercapnic acidosis attenuates endotoxin-induced acute lung injury

Permissive hypercapnia -role in protective lung ventilatory strategies

Observational study of humidifi ed high-fl ow nasal cannula compared with nasal continuous positive airway pressure

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SCCM/ESICM/ACCP/ATS/SIS International Sepsis Defi nitions Conference

Empyema hospitalizations increased in US children despite pneumococcal conjugate vaccine

Transient hemodynamic effects of recruitment maneuvers in three experimental models of acute lung injury

Noninvasive ventilation in children: a review

Clinical review: positive endexpiratory pressure and cardiac output

Dengueassociated adult respiratory distress syndrome

Successful management of ARDS with bronchopleural fi stula secondary to miliary tuberculosis using a conventional ventilator

Randomized trial of permissive hypercapnia in preterm infants

Effect of a high-fl ow open nasal cannula system on obstructive sleep apnea in children

Nasal CPAP treatment in an infant with respiratory syncytial virus-associated apnea

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Mechanical ventilation in children with acute respiratory failure

Serious adverse events during procedural sedation with ketamine

Acute lung injury and acute respiratory distress syndrome in malaria

BC Interdisciplinary Respiratory Protection Study Group (2005) Protecting health care workers from SARS and other respiratory pathogens: organizational and individual factors that affect adherence to infection control guidelines

A comprehensive review of pediatric endotracheal suctioning: effects, indications, and clinical practice

Possible role of increased oxidant stress in multiple organ failure after systemic infl ammatory response syndrome

Effect of mechanical ventilation strategy on dissemination of intratracheally instilled Escherichia coli in dogs

Manoeuvres to elevate mean airway pressure, effects on blood gases and lung function in children with and without pulmonary pathology

Hypercapnic acidosis attenuates severe acute bacterial pneumonia-induced lung injury by a neutrophil-independent mechanism

Humidifi cation policies for mechanically ventilated intensive care patients and prevention of ventilatorassociated pneumonia: a systematic review of randomized controlled trials

Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

Transmission of airway pressure to pleural space during lung edema and chest wall restriction

Concept of PIRO as a new conceptual framework to understand sepsis

The host response to endotoxin, antilipopolysaccharide strategies, and the management of severe sepsis

Pathology and pathogenesis of fatal Bordetella pertussis infection in infants

Alveolar cell death in hyperoxia-induced lung injury

Rocuronium versus succinylcholine for rapid sequence induction intubation

Treatment of acute respiratory failure by helmet-delivered non-invasive pressure support ventilation in children with acute leukemia: a pilot study

The infl uence of positive-pressure ventilation on cardiovascular function in the critically ill

The effects of mechanical ventilation on the cardiovascular system

Heart-lung interactions during positive-pressure ventilation

The hemodynamic consequences of mechanical ventilation: an evolving story

Heart-lung interactions

Pediatric non-invasive ventilation for acute respiratory failure in an Intermediate Care Unit

Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: a randomized controlled trial

Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma

Management of acute lung injury and acute respiratory distress syndrome in children

Role of non-invasive ventilation in diffi cult-to-wean children with acute neuromuscular disease

The effect of humidifi cation on the incidence of ventilatorassociated pneumonia

Lung recruitment during small tidal volume ventilation allows minimal positive endexpiratory pressure without augmenting lung injury

Routine suxamethonium in children. A regional survey of current usage

Pediatric rapid sequence intubation incidence of refl ex bradycardia and effects of pretreatment with atropine

Microvascular response to red blood cell transfusion in patients with severe sepsis

Oxidative stress in septic shock and disseminated intravascular coagulation

A prospective randomized controlled study of two fl uid regimens in the initial management of septic shock in the emergency department

Adult-to-child transmission of tuberculosis: household or community contact?

Mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome: an evidence-based review

Continuous negative extrathoracic pressure or continuous positive airway pressure for acute hypoxemic respiratory failure in children

Augmented lung injury due to interaction between hyperoxia and mechanical ventilation

Spectrum of chest radiographic abnormalities in children with AIDS and Pneumocystis carinii pneumonia

Pediatric parapneumonic pleural effusions: experience in a university central hospital

Children with respiratory distress treated with high-fl ow nasal cannula

Effect of core body temperature on ventilator-induced lung injury

Combined lung injury, meningitis and cerebral edema: how permissive can hypercapnia be?

Hyperoxia mediates acute lung injury and increased lethality in murine Legionella pneumonia: the role of apoptosis

Pulmonary manifestations of malaria: recognition and management

Non-invasive positive pressure ventilation: current status in paediatric patients

Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis

Hemodynamic and respiratory changes during lung recruitment and descending optimal positive end-expiratory pressure titration in patients with acute respiratory distress syndrome

Effects of positive intrathoracic pressure on pulmonary and systemic hemodynamics

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

Regional blood fl ow distribution in dog during induced hypotension and low cardiac output. Spontaneous breathing versus artifi cial ventilation

Anaesthesia for appendicectomy in childhood: a survey of practice in Northern Ireland

Necrotising pneumonitis in children

Research gaps in protecting healthcare workers from SARS and other respiratory pathogens: an interdisciplinary, multi-stakeholder, evidence-based approach

Collaborative Study Group of Pediatric Respiratory Failure (2009) The epidemiology of acute respiratory distress syndrome in pediatric intensive care units in China

Etomidate for rapid sequence intubation in the emergency department: is adrenal suppression a concern

Controversies in rapid sequence intubation in children

Incidence and outcomes of pediatric acute lung injury

Use of etomidate as an induction agent for rapid sequence intubation in a pediatric emergency department