541CHAPTER 48 Pediatric Acute Respiratory Distress Syndrome and Ventilator Associated Lung Injury pressure (MAP) during high frequency ventilation may prevent atelectrauma by limiting cyclic opening a[.]
CHAPTER 48 Pediatric Acute Respiratory Distress Syndrome and Ventilator-Associated Lung Injury pressure (MAP) during high-frequency ventilation may prevent atelectrauma by limiting cyclic opening and closing of alveoli Limiting tidal stretch (by limiting tidal volume and/or peak inspiratory pressure) prevents overdistention, particularly of relatively spared alveoli with shorter inspiratory time constants Despite these theoretical constructs, there is limited high-level evidence regarding the optimal methods or targets to achieve these strategies in children Considerations for Ventilator Mode There is limited evidence to support that one mode of ventilation is superior to another for PARDS However, volume control (constant flow pattern), used in the ARDS Network ARMA trial in adults, is infrequently used in pediatrics in favor of a decelerating flow pattern of pressure control or volume-targeted pressure control.138–141 This factor, among others, may limit the direct applicability of adult ARDS data to pediatrics However, regardless of the mode of ventilation, the principles of lung-protective ventilation are applicable and should be used for children with ARDS Tidal Volume The benefits of targeted Vt ventilation were established in the landmark ARDS Network ARMA trial.141 Mortality was reduced by 22% in the group receiving Vt of mL/kg ideal body weight (IBW) compared with patients receiving Vt of 12 mL/kg IBW Unlike the adult population, the pediatric data are inconclusive without a randomized control trial for Vt Observational pediatric studies have previously demonstrated lower mortality for patients treated with higher Vt to 10 mL/kg.142 This is likely due to Vt commonly being a dependent versus the set variable in pediatric mechanical ventilation Higher Vt for a set pressure represents better respiratory system compliance, implying that the patient is less ill Location of measurement of Vt (proximal airway vs at the ventilator without compensation for ventilator tubing compliance), IBW versus actual body weight, and correction for leakage around endotracheal tubes are practice differences between adult and pediatric ICU providers that complicate extrapolation of adult Vt data to children.143 Nevertheless, current recommendations advocate use of Vt in or below the physiologic range (5–8 mL/kg) IBW, with lower Vt targets in children with more compromised respiratory system compliance.144 Peak or Plateau Pressure There is sparse evidence to support a limit for peak or plateau pressure in pediatrics These terms are commonly interchanged when pressure control ventilation is used There may be few differences between peak and plateau pressure for children with ARDS managed with the decelerating flow pattern of pressure control ventilation if flow fully decelerates (dependent on inspiratory time and time constant of the lung) unless they concurrently have significant lower airway disease Measuring plateau pressure requires a period of no flow during inspiration (an inspiratory hold) This maneuver may not be implemented routinely or consistently in pediatric critical care, and “plateau” pressure is often mislabeled However, recent recommendations are to limit plateau pressure to 28 cm H2O for children with normal chest wall compliance, allowing slightly higher pressures when chest wall compliance is reduced.144 Ultimately, the shear stress induced by positive pressure ventilation is a function of transpulmonary pressure (alveolar pressure minus pleural pressure), potentially affording 541 the use of higher inspiratory pressure when pleural pressure is also increased (e.g., obesity, anasarca) Vt often gets the most attention, but the ARDS Network lung-protective mL/kg strategy recommends decreasing Vt below mL/kg if needed to limit plateau pressure to 30 cm H2O.141 High-driving pressure (difference between plateau pressure and PEEP), independent of both plateau pressure and Vt, is associated with higher mortality in adults with ARDS.145 Positive End-Expiratory Pressure PEEP should be set to prevent lung collapse and recruitmentderecruitment injury during tidal ventilation Unfortunately, given the heterogeneity of lung disease in PARDS, it is difficult to use this principle to guide specific PEEP recommendations for individual patients The optimal method to set PEEP for an individual patient remains a research question, and existing data not support a single PEEP level (high or low) that improves outcome for adults or children with ARDS Adult studies that protocolize PEEP/Fio2 for oxygenation targets support higher levels of PEEP.146,147 Recent adult data suggest that transpulmonary pressure-guided PEEP via esophageal pressure measurements rendered no mortality benefit compared with empirical high PEEP/ Fio2.148 Adult studies of recruitment maneuvers combined with increased PEEP were the rationale for a multicenter, phase II randomized controlled trial in adults that did not improve ventilator-free days.149 A novel approach has been used to determine the ratio of the compliance of recruited lung versus “baby lung” during expiration, which may be a functional test of determining responders to higher PEEP.150 Pediatric practice appears highly variable with respect to PEEP application, and PEEP is uncommonly increased to levels frequently used in adults with ARDS.151,152 In a study of pediatric patients with PARDS, 27% were managed with lower PEEP relative to the amount recommended by the ARDS Network PEEP/ Fio2 protocol, and lower PEEP was independently associated with increased mortality among these patients.153 Pediatric evidence is lacking, but moderately elevated levels of PEEP (10–15 cm H2O) titrated to oxygenation and hemodynamic responses are recommended for children with severe PARDS, with potential for higher levels of PEEP in the most severe patients.144 Importantly, plateau pressure should still be limited, and markers of oxygen delivery, respiratory system compliance, and hemodynamics should be closely monitored as PEEP is increased Nonconventional Ventilation Strategies Various forms of nonconventional ventilation modes are considered for children with PARDS, particularly those with severe disease The most common nonconventional mode is high-frequency oscillatory ventilation (HFOV) Although many practitioners use HFOV in PARDS, there are no data supporting improved outcomes; however, there are data suggesting improved gas exchange As such, HFOV is frequently used as a rescue modality The concept of HFOV is to ventilate with Vt approximating the anatomic dead space, leading many to believe that it is an optimal form of lung-protective ventilation that should be considered earlier in the course of ARDS However, animal studies suggest that treatment with high amplitude combined with low frequency can deliver high convective Vt and cause ventilator-associated lung injury.154–156 Recent adult and observational pediatric data not support use 542 S E C T I O N V Pediatric Critical Care: Pulmonary of HFOV early in ARDS.157–160 Current recommendations are to consider HFOV for patients with moderate to severe ARDS when adequate gas exchange cannot be maintained without exceeding suggested limits of plateau pressure (i.e., when lung protection cannot be maintained with conventional ventilation).144 However, optimal strategies to guide management of the different ventilator parameters on HFOV are an active area of investigation, with an ongoing pediatric interventional clinical trial investigating the use of HFOV on the outcomes of children with ARDS Alternative modes of nonconventional ventilation, such as airway pressure release ventilation (APRV) and high frequency jet ventilation (HFJV), may have some theoretical benefit for patients with moderate to severe ARDS, but there are no controlled data demonstrating their superiority to conventional modes of ventilation or HFOV for children with PARDS Ventilator-Associated Lung Injury Mechanical ventilation is the lifesaving support for patients with ARDS The earliest observations of ARDS suggested that adding PEEP improved survival, and limiting Vt remains the single most significant improvement to the care of patients with ARDS.141,161 However, the converse is also true—mechanical ventilation may worsen lung injury.162 Ventilator-associated lung injury (VALI) describes the potential contribution of mechanical ventilation to patients with existing lung injury; ventilator-induced lung injury (VILI) is used to describe injury directly caused by mechanical forces Many carefully designed laboratory studies have established multiple mechanisms by which the mechanical forces imposed on the respiratory system cause injuries in the lungs, but, because all patients with ARDS have a known clinical insult, VALI will be used throughout the rest of this chapter VALI may occur by shear stretch (volutrauma), repeated opening and closing of atelectatic lung (atelectrauma), production of proinflammatory cytokines via mechanotransduction (biotrauma), and oxidative stress.163,164 Barotrauma is a term that continues to be used to describe lung injury resulting in air leaks (pneumothorax, pneumomediastinum, and so on) as well as lung injury associated with high airway pressure However, barotrauma is likely somewhat of a misnomer, as an elegant study by Dreyfuss and Saumon showed that pressure, in the absence of high absolute lung volume, did not cause lung injury.165 The apparent discrepancy between volutrauma and barotrauma in the ARDS patient with significant portions of derecruited lung and high airway pressures can be reconciled by recognizing that, in heterogeneous lung disease, the energy of each Vt is delivered to only the fraction of lung that inflates.166,167 Amato’s work, showing that driving pressure was the variable that most accurately stratified risk, is consistent with the concept that mechanical power is the sum of the forces needed to recruit atelectatic and stretch inflated regions, divided by the time in which those forces are applied.145,168,169 This can be thought of as two related concepts: stress and strain.170–172 The stress of the lung is characterized by the driving pressure or, more precisely, the transpulmonary driving pressure This should be limited The strain is characterized by the Vt applied/FRC Hence, patients with more atelectasis and lower FRC will be more subject to strain-related injury with higher Vt ventilation than those with more normal levels of FRC This reinforces the importance of reducing the Vt (and driving pressure) for those with the most severe disease, where FRC is most reduced PEEP and prone positioning have the potential to recruit atelectatic regions and thereby reduce the fraction of tidal stretch delivered to individual lung regions by increasing the total amount of inflated lung (i.e., improving FRC and potentially reducing strain).173,174 This is the most likely physiologic rationale for studies that have shown improved outcomes in adult and pediatric patients with ARDS treated with higher PEEP.153,175 However, if additional PEEP does not recruit atelectatic regions, then the remaining lung regions will rest at higher levels of inflation at end expiration and the fractional tidal stretch will be increased, thus, worsening volutrauma.176 In a study of children with ARDS, airway pressures were inadequate measures of stress and strain.177 Although HFOV has the potential to improve lung recruitment with elevated MAPs and avoid volutrauma by delivering ultra-low, subphysiologic dead space Vt, it may also cause VALI The HFOV frequency is inversely related to convective Vt Considering that the inspiratory time in which that Vt is delivered is very short, there is potential for disproportionate forces to be applied to inflated lung.154,156,169,178 There are many benefits to having patients breathe spontaneously while being treated with mechanical ventilation, but high amounts of power, causing worse direct injury to the lung, may be difficult to discern during spontaneous breathing.179 In order to reduce the power delivered to the lung, there was early recognition that hypercapnia should be tolerated.180 Although data suggesting that hypercapnia may even be therapeutic, patient dyspnea from the attendant respiratory acidosis remained a barrier to effective implementation of “lung-protective ventilation.”180,181 Significant negative inspiratory forces generated at a high rate by the dyspneic patient with lung injury are likely to contribute to VALI—this situation is often called P-SILI for patient selfinduced (or inflicted) lung injury.179,182 Pulmonary Ancillary Therapies Exogenous Surfactant The efficacy of exogenous surfactant for PARDS may depend on the concentration of individual surfactant proteins and other phospholipids.80,82 Recent investigations have used exogenous surfactant preparations rich in either SP-B or SP-C given their direct properties on alveolar surface tension.183–185 Preclinical or Adult Data Lung injury studies in animals suggest that exogenous surfactant improves oxygenation, pulmonary compliance, alveolar edema, total lung water, and alveolar protein concentrations; plus, it may have an effect on lung inflammation.186–190 Heterogeneous patient populations and study designs make interpreting adult data difficult Exogenous surfactant appears to transiently improve oxygenation without affecting mortality, but some studies suggest harm related to adverse events such as hypoxemia (7%–50%), hypotension (9%–35%), transient airway obstruction, or rare events such as bradycardia, leukopenia, air leak syndrome and pneumonia.183,191–196 Post-hoc analyses suggesting that treatment with recombinant protein-C surfactant benefited the subgroup of adults with ARDS due to direct injury were not confirmed in subsequent randomized trials.183,197–199 Pediatric Data Early pediatric studies of exogenous surfactant for ARDS showed improvements in oxygenation and suggested reduced duration of ventilation and reduced mortality.200 Unfortunately, subsequent multicenter, randomized, placebo-controlled, blinded trials of calfactant did not show improved mortality or ventilator-free days.185,193 CHAPTER 48 Pediatric Acute Respiratory Distress Syndrome and Ventilator-Associated Lung Injury A phase II placebo-controlled, double-blind, randomized controlled trial of a synthetic surfactant preparation (lucinactant) that mimics the actions of SP-B was performed in 165 nonpremature children with persistent hypoxemia.184 The most common diagnoses were bronchiolitis and pneumonia, and only 37 children met criteria for ARDS Lucinactant was shown to be safe and improved oxygenation, but without an effect on duration of mechanical ventilation or mortality In summary, there is no evidence to suggest that exogenous surfactant reduces mortality for children or adults with ARDS Exogenous surfactant can be safely administered in children, and oxygenation may transiently improve The effects of surfactant seem to be confounded by the dosing regimen, drug delivery, drug concentration, surfactant formulation, degree of lung recruitment, lung disease severity, etiology of ARDS, comorbidities, and a multitude of other factors Future research is warranted to identify whether subgroups of patients benefit from exogenous surfactant Nitric Oxide Physiologic Rationale Nitric oxide (NO) is normally synthesized in the vascular endothelium and causes vasodilation by relaxing smooth muscle via intracellular cyclic guanosine monophosphate (cGMP) Nitric oxide also affects inflammation by altering endothelial interactions with leucocytes and platelets Since inhaled NO (iNO) is theoretically delivered only to ventilated lung units, its major effect is improved V/Q by increasing blood flow to ventilated units, thereby reducing physiologic dead space and improving oxygenation.201,202 iNO may also be important for lowering pulmonary vascular resistance and supporting the right ventricle in patients with ARDS and pre-existing pulmonary hypertension.203–208 Preclinical and Adult Studies In addition to effects on pulmonary vascular resistance, animal data suggest that iNO may both aggravate and ameliorate lung injury Some lung injury models show that iNO reduces neutrophil migration and oxidative burst, decreases lung inflammation, decreases platelet aggregation, and promotes lung repair.209–216 iNO may also improve pulmonary bacterial clearance through mechanisms related to endothelial permeability.217,218 Other models suggest that iNO has no salutary effect or may potentiate lung injury through proinflammatory mechanisms.219–222 Meta-analyses of iNO for adults with ARDS suggest that iNO does not reduce mortality.223,224 Most studies demonstrate transient improvements in oxygenation within the first 24 hours, but there may be an increased risk of renal impairment (relative risk [RR], 1.59; 95% confidence interval [CI], 1.17–2.16) among adults treated with iNO as compared with controls Despite these challenges, iNO continues to be used as a rescue therapy.225 Pediatric There have been a number of uncontrolled trials and small randomized controlled trials demonstrating improvements in oxygenation but not mortality or duration of ventilation with iNO administration for children with ARDS or acute hypoxemic respiratory failure.208,223,224,226–230 A third small randomized controlled trial on 32 children with ARDS examined the potential synergistic effects of prone positioning and iNO, demonstrating more sustained improvements in oxygenation with the combination of prone positioning and iNO over the first 24 hours of ventilation.231 A recent multicenter trial has shown that iNO 543 reduced the length of mechanical ventilation, mostly through lower use of ECMO.232 Unlike in adult studies, there does not appear to be evidence of significant toxicity with iNO administration in pediatric ARDS Pediatric and adult evidence suggest that iNO is probably best reserved for situations in which refractory hypoxemia needs to be temporarily ameliorated (e.g., as a bridge to extracorporeal support) or for patients with a true clinical indication, such as documented pulmonary hypertension with right heart dysfunction.233 Nonpulmonary Therapies Prone Positioning Physiologic Rationale The best described and cited rationale for placing patients with ARDS in the prone position is to improve regional V/Q matching due to more uniform distribution of aerated lung, particularly in dorsal lung regions, thereby reducing physiologic dead space and improving oxygenation.234,235 The effects of prone positioning on gas exchange are conventionally thought to be due to gravitational effects on the distribution of atelectasis and edema as well as the effects of the weight of the heart and position of the dorsal diaphragm on the expansion of dorsal lung units.236,237 Interestingly, prone positioning also appears to improve the cephalocaudal distribution of ventilation, because the heart, mediastinal structures, and abdominal contents rest on the sternum The prone position reduces regional differences in pleural pressure near the diaphragm that are normally present when upright or supine.237–240 Prone positioning may also reduce inequalities in regional time constants and promote more effective alveolar ventilation to “slower” compartments.241,242 These effects ultimately may influence lung strain and reduce the development of VALI.243,244 When used in conjunction with high PEEP strategies currently recommended for ARDS, prone positioning may also increase alveolar recruitment and prevent cyclic recruitment/derecruitment and atelectrauma.245 Minimizing derecruitment may be a physiologic explanation of why additional recruitment strategies such as HFOV sustain temporary improvements obtained during prone positioning.246 Patients with more compliant chest walls may have more benefit from prone positioning due to the reduction in chest wall compliance caused by limiting expansion of the sternum This reduction in chest wall compliance, in addition to decreasing compression of the lungs by the heart and decreasing the vertical pleural pressure gradient in the lungs, theoretically allows preferential distribution of ventilation to the dorsal lung.237 However, there is contradictory evidence for this mechanism and the overall effect of chest wall properties on the oxygenation response to prone positioning of ARDS patients.247 It is also important to note that none of these studies was performed in children Other potential mechanisms for the beneficial effects of prone positioning include improved airway secretion clearance and lowering pulmonary artery pressure via attenuation of hypoxic pulmonary vasoconstriction However, due to compromised preload, this effect may not directly translate into improvements in cardiac index.237,248,249 Adult Data Adult data demonstrate that the gas exchange response to prone positioning is not universal and benefits only a subset of patients.237,250,251 Moreover, the immediate improvement in oxygenation is inconsistently associated with a survival advantage 544 S E C T I O N V Pediatric Critical Care: Pulmonary in adults with ARDS.252–254 However, prone positioning has been associated with improved survival in adults for whom dead space ventilation improved.255,256 There have been numerous randomized controlled trials of prone positioning for ARDS in adults.252,254,257–262 Meta-analyses highlight heterogeneity in these trials due to duration of prone positioning, use of concurrent lung-protective ventilation, Vt, hypoxemia severity, use of HFOV, and duration of respiratory failure prior to prone positioning.261,262 Nevertheless, these metaanalyses concluded that prone positioning affords a survival advantage for adults with ARDS, with the effect most pronounced in those who receive a longer duration of prone positioning, are managed with lung-protective ventilation strategies with regard to PEEP and Vt, and who have more severe lung injury and hypoxemia However, when pooling the adverse events, those in the prone-positioning group had a higher incidence of pressure ulcers, airway problems, and endotracheal tube obstruction.261 The PROSEVA trial in adults is a major driver of the conclusions with regard to survival advantage in patients positioned prone.258 Prone positioning was maintained for a minimum of 16 consecutive hours, and ventilator management was standardized with a lung protective ventilation protocol Mortality was 32.8% in the supine group, and 16% in the prone group at 28 days (P , 001) Unlike other studies, there were no increased adverse events in the prone group as compared with controls The study suggests that prone positioning may benefit adults with severe ARDS when done by experienced providers, long consecutive duration of prone positioning, and meticulous lung protective ventilation Pediatric Data The results of the Proning Severe ARDS Patients (PROSEVA) trial question existing data on prone positioning in children Multiple uncontrolled trials and one randomized controlled trial on prone positioning have not demonstrated a survival advantage in children with ARDS.263–267 The highest level of pediatric evidence comes from a multicenter randomized controlled trial from 2005, which had detailed multidisciplinary protocols and guidelines for lung-protective ventilation, sedation, extubation readiness, hemodynamic support, nutrition, and skin care.268,269 This unblinded clinical trial was stopped early secondary to futility: there were no differences in the primary outcome of ventilator-free days or the secondary outcomes of mortality, time to recovery of lung injury, organ failure, cognitive impairment, or functional health Most of those patients would now be considered to have moderate ARDS; at the time that study procedures began, nearly half of the children had P/F ratios greater than 150 These results may be further confounded because adult data support more benefit from prone positioning for those with severe hypoxemia Finally, while theory supports that children may have more pronounced benefits from prone positioning due to chest wall compliance, this benefit may be limited by less substantial compression of the lungs by the heart when supine as compared with adults Future studies may benefit from the inclusion of measurements of transpulmonary pressure gradients and chest wall versus static lung compliance changes with prone positioning There is an active pediatric interventional clinical trial investigating the use of prone positioning on the outcomes of children with severe ARDS Monitoring Pediatric patients with or at risk of PARDS should receive at least clinical monitoring of respiratory frequency, heart rate, continuous pulse oximetry, and noninvasive blood pressure.270 Exhaled Vt should be measured at the endotracheal tube, especially in the smallest patients, or corrected for tubing compliance if measured at the ventilator Exhaled Vt should likely be normalized to IBW, although spinal deformities and contractures may complicate measurement of height for calculation of ideal body weight in some patients Inspiratory pressure (peak pressure in pressure modes, and plateau pressure in volume modes), flow, and volume should be measured continuously Continuous monitoring of Spo2 (with titration of Fio2 titrated to keep Spo2 #97%), PEEP, and MAP are essential to diagnose PARDS and monitor disease progression Continuous capnography is important to determine the adequacy of support provided and to monitor physiologic dead space, which is associated with disease severity Arterial blood sampling may be required when the accuracy of noninvasive monitoring is insufficient, and placement of arterial catheters may be indicated for hemodynamic assessments Standard plainfilm chest radiographs are indicated for diagnosis, determining appropriate position of equipment, and diagnosis of complications (e.g., pneumothorax) Noninvasive Support Despite the widespread increased use of noninvasive support for pediatric and adult patients with acute respiratory failure, there is a paucity of data to determine the utility of these modes of respiratory support in ARDS Noninvasive support of patients with ARDS has theoretical benefits, including avoidance of complications of intubation, preservation of spontaneous breathing and airway clearance, and reduced need for sedation Noninvasive respiratory support can be considered for children with mild PARDS in a setting where trained and experienced staff can closely monitor for response to therapy and rapidly identify and treat deterioration.271 A multicenter observational study of children with PARDS suggests that approximately half of children with PARDS who are initially treated with NIV are intubated; mortality in these patients is similar to those with moderate to severe PARDS.28 Although this study showed that some children with PARDS can be managed without invasive ventilation, at this time there is not a means to determine which children will require intubation However, the severity of underlying disease and an early response to noninvasive support appear to be primary determinants of success Presence of a second organ failure, Fio2 greater than 0.6 or Spo2:Fio2 ratio less than 190, high severity of illness scores (Pediatric Logistic Organ Dysfunction [PELOD] or Pediatric Risk of Mortality [PRISM]), or moderate to severe ARDS suggest that noninvasive support will not be sufficient.271–274 Once a patient is started on noninvasive support for respiratory failure, the patient must be closely monitored for clinical response Failure to respond to noninvasive respiratory support within the first few hours has been associated with need for intubation, higher complication rates at the time of intubation, and higher mortality in adults Evidence that a patient has failed to respond to noninvasive respiratory support may include absence of reduction in respiratory rate, pH less than 7.25 after hours, increased oxygen requirement (Fio2 80% after hour), a decreased P/F ratio or an S/F ratio less than 190, an increase of PaCO2, or an altered level of consciousness.271,274 However, patients with very high respiratory drive may also be at high risk for poor outcome when left on NIV, by exacerbating P-SILI Adult data, in fact, support worse outcomes for ARDS patients who CHAPTER 48 Pediatric Acute Respiratory Distress Syndrome and Ventilator-Associated Lung Injury achieve higher Vt when on NIV This is a population of pediatric patients and mode of support that requires study, as it is not clear whether early identification of patients that will require invasive mechanical ventilation could be more safely managed by avoiding noninvasive support with high patient work of breathing Extracorporeal Life Support There are data from clinical trials of extracorporeal life support (ECLS) for neonates and adults with severe respiratory failure, but none in children Data from the Extracorporeal Life Support Organization (ELSO) registry indicates that the average survival of more than 7000 children treated with ECLS for respiratory failure is 58%.275 ECLS should be considered for children with severe PARDS from reversible causes in centers with clearly defined ECLS teams.276 Clinical factors, including lower precannulation blood pH and precannulation mechanical ventilatory support greater than weeks was associated with higher mortality.277 In a large cohort study involving 2449 children, children with severe ARDS treated with ECMO did not have better outcomes relative to children with severe ARDS who were not treated with ECMO.278 Improvements in diagnosis and risk stratification of PARDS will provide a means to perform better comparative effectiveness trials for ECLS with “lung rest” versus conventional lung protective ventilation.279–281 545 Key References Amato MBP, Meade MO, Slutsky AS, et al Driving pressure and survival in the acute respiratory distress syndrome N Engl J Med 2015; 372(8):747-755 Beitler JR, Shaefi S, Montesi SB, et al Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis Intensive Care Med 2014;40(3):332-341 Khemani RG, Smith LS, Zimmerman JJ, Erickson S, et al Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the pediatric acute lung injury consensus conference Pediatr Crit Care Med 2015;16(5 suppl):S23-S40 Khemani RG, Smith L, López-Fernández YM, et al Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study Lancet Respir Med 2019;7(2):115-128 Marini JJ, Rocco PRM, Gattinoni L Static and dynamic contributors to VILI in clinical practice: pressure, energy, and power Am J Respir Crit Care Med 2020;201(7):767-774 The Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, et al Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome N Engl J Med 2000;342(18):1301-1308 The Pediatric Acute Lung Injury Consensus Conference Group Pediatric acute respiratory distress syndrome: consensus recommendations from the pediatric acute lung injury consensus conference Pediatr Crit Care Med 2015;16(5):428-439 The full reference list for this chapter is available at ExpertConsult.com ... those with moderate to severe PARDS.28 Although this study showed that some children with PARDS can be managed without invasive ventilation, at this time there is not a means to determine which... and stretch inflated regions, divided by the time in which those forces are applied.145,168,169 This can be thought of as two related concepts: stress and strain.170–172 The stress of the lung... is characterized by the driving pressure or, more precisely, the transpulmonary driving pressure This should be limited The strain is characterized by the Vt applied/FRC Hence, patients with more