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Background: Mechanical power is a summary variable quantifying the risk of ventilator-induced lung injury. The original mechanical power equation was developed using square flow ventilation. However, most children are ventilated using decelerating flow. It is unclear whether mechanical power differs according to mode of flow delivery. This study compared mechanical power in children with acute respiratory distress syndrome who received both square and decelerating flow ventilation., Methods: This was a secondary analysis of a prospectively enrolled cohort of pediatric acute respiratory distress syndrome. Patients were ventilated on decelerating flow and then placed in square flow and allowed to stabilize. Ventilator metrics from both modes were collected within 24 h of acute respiratory distress syndrome onset. Paired t tests were used to compare differences in mechanical power between the modes., Results: This study enrolled 185 subjects with a median oxygenation index of 9.5 (interquartile range, 7 to 13) and median age of 8.3 yr (interquartile range, 1.8 to 14). Mechanical power was lower in square flow mode (mean, 0.46 J · min-1 · kg-1; SD, 0.25; 95% CI, 0.42 to 0.50) than in decelerating flow mode (mean, 0.49 J · min-1 · kg-1; SD, 0.28; 95% CI, 0.45 to 0.53) with a mean difference of 0.03 J · min-1 · kg-1 (SD, 0.08; 95% CI, 0.014 to 0.038; P < 0.001). This result remained statistically significant when stratified by age of less than 2 yr in square flow compared to decelerating flow and also when stratified by age of 2 yr or greater in square flow compared to decelerating flow. The elastic contribution in square flow was 70%, and the resistive contribution was 30%., Conclusions: Mechanical power was marginally lower in square flow than in decelerating flow, although the clinical significance of this is unclear. Upward of 30% of mechanical power may go toward overcoming resistance, regardless of age. This is nearly three-fold greater resistance compared to what has been reported in adults., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Pediatric ARDS is associated with significant morbidity and mortality. High-quality data from clinical trials in children are limited due to numerous barriers to their design and execution. Here we describe the collaborative development of a master protocol as a tool to address some of these barriers and support the conduct of pediatric ARDS studies., Methods: Using PubMed, we performed a literature search of randomized controlled trials (RCTs) in pediatric ARDS to characterize the current state and evaluate potential benefit of harmonized master protocols. We used a multi-stakeholder, collaborative, and team science-oriented process to develop a master protocol template with links to common data elements (CDEs) for pediatric ARDS trials., Results: We identified 11 RCTs that enrolled between 14-200 total subjects per trial. Interventions included mechanical ventilation, prone positioning, corticosteroids, and surfactant. Studies displayed significant heterogeneity in ARDS definition, design, inclusion and exclusion criteria, and reported outcomes. Mortality was reported in 91% of trials and ventilator-free days in 73%. The trial heterogeneity made pooled analysis unfeasible. These findings underscore the need for a method to facilitate combined analysis of future trials through standardization of trial elements. As a potential solution, we developed a master protocol, iteratively revised with input from a multidisciplinary panel of experts and organized into 3 categories: instructions and general information, templated language, and a series of text options of common pediatric ARDS trial scenarios. Finally, we linked master protocol sections to relevant CDEs previously defined for pediatric ARDS and captured in a series of electronic case report forms., Conclusions: The majority of pediatric ARDS trials identified were small and heterogeneous in study design and outcome reporting. Using a master protocol template for pediatric ARDS trials with CDEs would support combining and comparing pediatric ARDS trial findings and increase the knowledge base., Competing Interests: Mr Miller discloses a relationship with Fisher and Paykel, S2N Health, MedEx Research, and Aerogen. Mr Miller is a section editor for Respiratory Care. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Objectives: The Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model (PARDSEVERE) used age and three plasma biomarkers measured within 24 hours of pediatric acute respiratory distress syndrome (ARDS) onset to predict mortality in a pilot cohort of 152 patients. However, longitudinal performance of PARDSEVERE has not been evaluated, and it is unclear whether the risk model can be used to prognosticate after day 0. We, therefore, sought to determine the test characteristics of PARDSEVERE model and population over the first 7 days after ARDS onset., Design: Secondary unplanned post hoc analysis of data from a prospective observational cohort study carried out 2014-2019., Setting: University-affiliated PICU., Patients: Mechanically ventilated children with ARDS., Interventions: None., Measurements and Main Results: Between July 2014 and December 2019, 279 patients with ARDS had plasma collected at day 0, 266 at day 3 (11 nonsurvivors, two discharged between days 0 and 3), and 207 at day 7 (27 nonsurvivors, 45 discharged between days 3 and 7). The actual prevalence of mortality on days 0, 3, and 7, was 23% (64/279), 14% (38/266), and 13% (27/207), respectively. The PARDSEVERE risk model for mortality on days 0, 3, and 7 had area under the receiver operating characteristic curve (AUROC [95% CI]) of 0.76 (0.69-0.82), 0.68 (0.60-0.76), and 0.74 (0.65-0.83), respectively. The AUROC data translate into prevalence thresholds for the PARDSEVERE model for mortality (i.e., using the sensitivity and specificity values) of 37%, 27%, and 24% on days 0, 3, and 7, respectively. Negative predictive value (NPV) was high throughout (0.87-0.90 for all three-time points)., Conclusions: In this exploratory analysis of the PARDSEVERE model of mortality risk prediction in a population longitudinal series of data from days 0, 3, and 7 after ARDS diagnosis, the diagnostic performance is in the "acceptable" category. NPV was good. A major limitation is that actual mortality is far below the prevalence threshold for such testing. The model may, therefore, be more useful in cohorts with higher mortality rates (e.g., immunocompromised, other countries), and future enhancements to the model should be explored., Competing Interests: Drs. Whitney and Varisco received support for article research from the National Institutes of Health (NIH). Dr. Varisco received funding from Society of Critical Care Medicine Discovery Award 2020 (R01HL141229). Dr. Raby received support for article research from the NIH (R01HL130974, R01HL118455, P01HL132825, P01HL114501, R01HL118455, RK08HL155892, U01AI160087, U19AI095219, and U01TR001810); he received funding from Chan Zuckerberg Initiative 2022-316770, UpToDate, and royalties as Genetics Section Editor. Dr. Yehya’s institution received funding from the National Heart, Lung, and Blood Institute and the NIH (K23HL136688 and R01HL148054); he received funding from AstraZeneca. Ms. Johnson has disclosed that she does not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Fluid overload is associated with worse outcomes in adult and pediatric acute respiratory distress syndrome. However, the time-course of fluid overload and its relationship to outcome has not been described. We aimed to determine the relationship between the timing of fluid overload and outcomes over the first 7 days after acute respiratory distress syndrome onset in children., Design: Retrospective cohort study., Setting: Single tertiary care PICU., Patients: Intubated children with acute respiratory distress syndrome between 2011 and 2019., Interventions: None., Measurements and Main Results: Daily and cumulative total fluid intake, total output, urine output, and fluid balance were collected for each 24-hour period from days 1 to 7 after acute respiratory distress syndrome onset. We tested the association between daily cumulative fluid metrics with PICU mortality and probability of extubation by 28 days using multivariable logistic and competing risk regression, respectively. In a subset of children, plasma was collected on day 1 and day 3 of acute respiratory distress syndrome and angiopoietin-2 quantified. Of 723 children with acute respiratory distress syndrome, 132 died (18%). In unadjusted analysis, nonsurvivors had higher cumulative fluid balance starting on day 3. In multivariable analysis, a positive cumulative fluid balance on days 5 through 7 was associated with increased mortality. Higher cumulative fluid balance on days 4 to 7 was associated with lower probability of extubation. Elevated angiopoietin-2 on day 1 predicted early (within 3 d) fluid overload greater than or equal to 10%, and elevated angiopoietin-2 on day 3 predicted late (between days 4 and 7) fluid overload., Conclusions: Fluid overload after day 4 of acute respiratory distress syndrome, but not before, was associated with worse outcomes. Higher angiopoietin-2 predicted subsequent fluid overload. Our results suggest that future interventions aimed at managing fluid overload may have differential efficacy depending on when in the time-course of acute respiratory distress syndrome they are initiated., Competing Interests: Dr. Yehya’s institution received funding from the National Institutes of Health (NIH) and Pfizer; he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: There is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors., Design: Secondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days., Setting: Large academic tertiary-care PICU., Patients: Children with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation., Interventions: Implementation of a ventilator-weaning pathway on May 2016., Measurements and Main Results: Of 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders., Conclusions: Ventilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials., Competing Interests: Dr. Yehya’s institution received funding from the National institutes of Health (NIH), and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Mechanical power and driving pressure have been proposed as indicators, and possibly drivers, of ventilator-induced lung injury. We tested the utility of these different measures as targets to derive maximally protective ventilator settings., Design: A high-fidelity computational simulator was matched to individual patient data and used to identify strategies that minimize driving pressure, mechanical power, and a modified mechanical power that removes the direct linear, positive dependence between mechanical power and positive end-expiratory pressure., Setting: Interdisciplinary Collaboration in Systems Medicine Research Network., Subjects: Data were collected from a prospective observational cohort of pediatric acute respiratory distress syndrome from the Children's Hospital of Philadelphia (n = 77) and from the low tidal volume arm of the Acute Respiratory Distress Syndrome Network tidal volume trial (n = 100)., Interventions: Global optimization algorithms evaluated more than 26.7 million changes to ventilator settings (approximately 150,000 per patient) to identify strategies that minimize driving pressure, mechanical power, or modified mechanical power., Measurements and Main Results: Large average reductions in driving pressure (pediatric: 23%, adult: 23%), mechanical power (pediatric: 44%, adult: 66%), and modified mechanical power (pediatric: 61%, adult: 67%) were achievable in both cohorts when oxygenation and ventilation were allowed to vary within prespecified ranges. Reductions in driving pressure (pediatric: 12%, adult: 2%), mechanical power (pediatric: 24%, adult: 46%), and modified mechanical power (pediatric: 44%, adult: 46%) were achievable even when no deterioration in gas exchange was allowed. Minimization of mechanical power and modified mechanical power was achieved by increasing tidal volume and decreasing respiratory rate. In the pediatric cohort, minimum driving pressure was achieved by reducing tidal volume and increasing respiratory rate and positive end-expiratory pressure. The Acute Respiratory Distress Syndrome Network dataset had limited scope for further reducing tidal volume, but driving pressure was still significantly reduced by increasing positive end-expiratory pressure., Conclusions: Our analysis identified different strategies that minimized driving pressure or mechanical power consistently across pediatric and adult datasets. Minimizing standard and alternative formulations of mechanical power led to significant increases in tidal volume. Targeting driving pressure for minimization resulted in ventilator settings that also reduced mechanical power and modified mechanical power, but not vice versa.

Ventilator-free days (VFDs) are a commonly reported composite outcome measure in acute respiratory distress syndrome trials. VFDs combine survival and duration of ventilation in a manner that summarizes the "net effect" of an intervention on these two outcomes. However, this combining of outcome measures makes VFDs difficult to understand and analyze, which contributes to imprecise interpretations. We discuss the strengths and limitations of VFDs and other "failure-free day" composites, and we provide a framework for when and how to use these outcome measures. We also provide a comprehensive discussion of the different analytic methods for analyzing and interpreting VFDs, including Student's t tests and rank-sum tests, as well as competing risk regressions treating extubation as the primary outcome and death as the competing risk. Using simulations, we illustrate how the statistical test with optimal power depends on the relative contributions of mortality and ventilator duration on the composite effect size. Finally, we recommend a simple analysis and reporting framework using the competing risk approach, which provides clear information on the effect size of an intervention, a statistical test and measure of confidence with the ability to adjust for baseline factors and allow interim monitoring for trials. We emphasize that any approach to analyzing a composite outcome, including other "failure-free day" constructs, should also be accompanied by an examination of the components.

Objectives: The impact of tidal volume on outcomes in mechanically ventilated children with pediatric acute respiratory distress syndrome remains unclear. To date, observational investigations have failed to calculate tidal volume based on standardized corrections of weight. We investigated the impact of tidal volume on mortality and probability of extubation in pediatric acute respiratory distress syndrome using ideal body weight-adjusted tidal volume., Design: Retrospective analysis of an ongoing prospective cohort of pediatric acute respiratory distress syndrome patients. Tidal volume was calculated based on actual body weight and two different formulations of ideal body weight., Setting: PICU at a large, tertiary care children's hospital., Patients: Pediatric acute respiratory distress syndrome patients on conventional ventilation with a documented height or length., Interventions: None., Measurements and Main Results: There were 483 patients with a measured height or length at pediatric acute respiratory distress syndrome onset included in the final analysis, with 73 nonsurvivors (15%). At 24 hours, there remained 400 patients on conventional ventilation. When calculating tidal volume based on ideal body weight by either method, volumes were larger both at onset and at 24 hours compared with tidal volume based on actual body weight (all p < 0.001), and the proportion of patients being ventilated with tidal volumes greater than 10 mL/kg based on ideal body weight was larger both at onset (12.4% and 15.5%) and 24 hours (10.3% and 11.5%) compared with actual body weight at onset (3.5%) and 24 hours (4.0%) (all p < 0.001). Tidal volume, based on both actual body weight and ideal body weight, was not associated with either increased mortality or decreased probability of extubation after adjusting for oxygenation index in the whole cohort, whereas associations between higher tidal volume and poor outcomes were seen in subgroup analyses in overweight children and in severe pediatric acute respiratory distress syndrome., Conclusions: Our retrospective analysis of a cohort of pediatric acute respiratory distress syndrome patients did not find a consistent association between tidal volume adjusted for ideal body weight and outcomes, although an association may exist in certain subgroups. Although it remains to be shown in a prospective trial whether high volumes or pressures are injurious in pediatric acute respiratory distress syndrome, tidal volume is likely an imprecise parameter for titrating lung-protective ventilation.

Objectives: Investigations of acute respiratory distress syndrome in adults suggest hypoxemia is an uncommon cause of death. However, the epidemiology of death in pediatric acute respiratory distress syndrome is not well characterized. We aimed to describe the cause, mode, and timing of death in pediatric acute respiratory distress syndrome nonsurvivors. We hypothesized that most deaths would be due to nonpulmonary factors, rather than hypoxemia., Design: Retrospective, decedent-only analysis., Setting: Two large, academic PICUs., Patients: Nonsurvivors with pediatric acute respiratory distress syndrome., Interventions: None., Measurements and Main Results: Of 798 subjects with pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19% mortality). Median time to death was 6 days (interquartile range, 3-13 d) after pediatric acute respiratory distress syndrome onset. Patients dying less than 7 days after pediatric acute respiratory distress syndrome onset had greater illness severity and worse oxygenation. Patients dying less than 7 days were more likely to die of a neurologic cause, including brain death. Patients dying greater than or equal to 7 days after pediatric acute respiratory distress syndrome onset were more commonly immunocompromised. Multisystem organ failure predominated in deaths greater than or equal to 7 days. Withdrawal of therapy was the most common mode of death at all timepoints, accounting for 66% of all deaths. Organ dysfunction was common at time of death, irrespective of cause of death. Refractory hypoxemia accounted for only a minority of pediatric acute respiratory distress syndrome deaths (20%)., Conclusions: In pediatric acute respiratory distress syndrome, early deaths were due primarily to neurologic failure, whereas later deaths were more commonly due to multisystem organ failure. Deaths from neurologic causes accounted for a substantial portion of nonsurvivors. Refractory hypoxemia accounted for only a minority of deaths. Our study highlights limitations associated with using death as an endpoint in therapeutic pediatric acute respiratory distress syndrome trials.

Objectives: Much of the research related to pediatric acute respiratory distress syndrome has focused on inhospital mortality and interventions affecting this outcome. Limited data exist on survivors' morbidity, hospital disposition, and 1-year survival. The aim of this study was to determine new morbidity rate, discharge disposition, and 1-year mortality for survivors of pediatric acute respiratory distress syndrome., Design: Secondary analysis of prospective cohort study., Setting: Quaternary children's hospital., Patients: Three-hundred sixteen mechanically ventilated children with pediatric acute respiratory distress syndrome (Berlin and Pediatric Acute Lung Injury Consensus Conference criteria) between July 2011 and December 2014., Interventions: None., Measurements and Main Results: We performed secondary analysis of a prospectively recruited cohort of 316 mechanically ventilated children with pediatric acute respiratory distress syndrome between July 2011, and December 2014. Preillness and hospital discharge Functional Status Scale score were determined via chart review, and factors associated with new morbidity, defined as an increase of Functional Status Scale score of 3 or more, were analyzed. Demographic variables, pediatric acute respiratory distress syndrome characteristics, and ventilator management were tested for association with development of new morbidity, discharge disposition, and 1-year mortality. Inhospital mortality of pediatric acute respiratory distress syndrome was 13.3% (42/316). Of 274 survivors to hospital discharge, new morbidity was seen in 63 patients (23%). Discharge to rehabilitation rate was 24.5% (67/274) and associated with development of new morbidity. One- and 3-year mortality of survivors was 5.5% (15 deaths) and 8% (22 deaths) and was associated with baseline Functional Status Scale, immunocompromised status, Pediatric Risk of Mortality III, and organ failures at pediatric acute respiratory distress syndrome onset, but not with pediatric acute respiratory distress syndrome severity., Conclusions: New morbidity was common after pediatric acute respiratory distress syndrome and appears to be intermediate phenotype between survival without morbidity and death, making it a useful metric in future interventional and outcome studies in pediatric acute respiratory distress syndrome.

Objectives: Diaphragm atrophy is associated with delayed weaning from mechanical ventilation and increased mortality in critically ill adults. We sought to test for the presence of diaphragm atrophy in children with acute respiratory failure., Design: Prospective, observational study., Setting: Single-center tertiary noncardiac PICU in a children's hospital., Patients: Invasively ventilated children with acute respiratory failure., Measurements and Main Results: Diaphragm thickness at end-expiration and end-inspiration were serially measured by ultrasound in 56 patients (median age, 17 mo; interquartile range, 5.5-52), first within 36 hours of intubation and last preceding extubation. The median duration of mechanical ventilation was 140 hours (interquartile range, 83-201). At initial measurement, thickness at end-expiration was 2.0 mm (interquartile range, 1.8-2.5) and thickness at end-inspiration was 2.5 mm (interquartile range, 2-2.8). The change in thickness at end-expiration during mechanical ventilation between first and last measurement was -13.8% (interquartile range, -27.4% to 0%), with a -3.4% daily atrophy rate (interquartile range, -5.6 to 0%). Thickening fraction = ([thickness at end-inspiration - thickness at end-expiration]/thickness at end-inspiration) throughout the course of mechanical ventilation was linearly correlated with spontaneous breathing fraction (beta coefficient, 9.4; 95% CI, 4.2-14.7; p = 0.001). For children with a period of spontaneous breathing fraction less than 0.5 during mechanical ventilation, those with exposure to a continuous neuromuscular blockade infusion (n = 15) had a significantly larger decrease in thickness at end-expiration compared with children with low spontaneous breathing fraction who were not exposed to a neuromuscular blockade infusion (n = 18) (-16.4%, [interquartile range, -28.4% to -7.0%] vs -7.3%; [interquartile range, -10.9% to -0%]; p = 0.036)., Conclusions: Diaphragm atrophy is present in children on mechanical ventilation for acute respiratory failure. Diaphragm contractility, measured as thickening fraction, is strongly correlated with spontaneous breathing fraction. The combination of exposure to neuromuscular blockade infusion with low overall spontaneous breathing fraction is associated with a greater degree of atrophy.

Objective: Oxygenation measured 24 hours after acute respiratory distress syndrome onset more accurately stratifies risk, relative to oxygenation at onset, in both children and adults. However, waiting 24 hours is problematic, especially for interventions that are more efficacious early in the disease course. We aimed to delineate whether oxygenation measured at timepoints earlier than 24 hours would retain predictive validity in pediatric acute respiratory distress syndrome., Design: Observational cohort study., Setting: Two large, academic PICUs., Patients: Invasively ventilated children with acute respiratory distress syndrome., Interventions: None., Measurements and Main Results: PaO2/FIO2 and oxygenation index (mean airway pressure × FIO2 × 100)/PaO2) were measured at acute respiratory distress syndrome onset, at 6, 12, 18, and 24 hours after in 459 children at the Children's Hospital of Philadelphia. Neither PaO2/FIO2 nor oxygenation index at acute respiratory distress syndrome onset discriminated outcome. Between 6 and 24 hours, both PaO2/FIO2 (area under receiver operating curve for mortality between 0.57 and 0.62; p = 0.049-0.002) and oxygenation index (area under receiver operating curve, 0.60-0.62; p = 0.006-0.001) showed good discrimination and calibration across multiple outcomes, including mortality, ventilator-free days at 28 days, ventilator days in survivors, and probability of extubation, given competing risk of death. The utility of oxygenation at 12 hours was confirmed in an independent cohort from the Children's Hospital of Los Angeles., Conclusion: Oxygenation measured between 6 and 12 hours of acute respiratory distress syndrome onset accurately stratified outcomes in children. Our results have critical implications for the design of trials, especially for interventions with greater impact in early acute respiratory distress syndrome.

Objectives: Blood products are often transfused in critically ill children, although recent studies have recognized their potential for harm. Translatability to pediatric acute respiratory distress syndrome is unknown given that hypoxemia has excluded pediatric acute respiratory distress syndrome patients from clinical trials. We aimed to determine whether an association exists between blood product transfusion and survival or duration of ventilation in pediatric acute respiratory distress syndrome., Design: Retrospective analysis of prospectively enrolled cohort., Setting: Large, academic PICU., Patients: Invasively ventilated children meeting Berlin Acute Respiratory Distress Syndrome and Pediatric Acute Lung Injury Consensus Conference Pediatric Acute Respiratory Distress Syndrome criteria from 2011 to 2015., Interventions: We recorded transfusion of RBC, fresh frozen plasma, and platelets within the first 3 days of pediatric acute respiratory distress syndrome onset. Each product was tested for independent association with survival (Cox) and duration of mechanical ventilation (competing risk regression with extubation as primary outcome and death as competing risk). A sensitivity analysis using 1:1 propensity matching was also performed., Measurements and Main Results: Of 357 pediatric acute respiratory distress syndrome patients, 155 (43%) received RBC, 82 (23%) received fresh frozen plasma, and 92 (26%) received platelets. Patients who received RBC, fresh frozen plasma, or platelets had higher severity of illness score, lower PaO2/FIO2, and were more often immunocompromised (all p < 0.05). Patients who received RBC, fresh frozen plasma, or platelets had worse survival and longer duration of ventilation by univariate analysis (all p < 0.05). After multivariate adjustment for above confounders, no blood product was associated with survival. After adjustment for the same confounders, RBC were associated with decreased probability of extubation (subdistribution hazard ratio, 0.65; 95% CI, 0.51-0.83). The association between RBC and prolonged ventilation was confirmed in propensity-matched subgroup analysis., Conclusions: RBC transfusion was independently associated with longer duration of mechanical ventilation in pediatric acute respiratory distress syndrome. Hemoglobin transfusion thresholds should be tested specifically within pediatric acute respiratory distress syndrome to establish whether a more restrictive transfusion strategy would improve outcomes.

Objectives: Literature regarding appropriate use of inhaled nitric oxide for pediatric acute respiratory distress syndrome is sparse. This study aims to determine if positive response to inhaled nitric oxide is associated with decreased mortality and duration of mechanical ventilation in pediatric acute respiratory distress syndrome., Design: Retrospective cohort study., Setting: Large pediatric academic medical center., Patients or Subjects: One hundred sixty-one children with pediatric acute respiratory distress syndrome and inhaled nitric oxide exposure for greater than or equal to 1 hour within 3 days of pediatric acute respiratory distress syndrome onset., Interventions: Patients with greater than or equal to 20% improvement in oxygenation index or oxygen saturation index by 6 hours after inhaled nitric oxide initiation were classified as "responders.", Measurements and Main Results: Oxygenation index, oxygen saturation index, and ventilator settings were evaluated prior to inhaled nitric oxide initiation and 1, 6, 12, and 24 hours following inhaled nitric oxide initiation. Primary outcomes were mortality and duration of mechanical ventilation. Baseline characteristics, including severity of illness, were similar between responders and nonresponders. Univariate analysis showed no difference in mortality between responders and nonresponders (21% vs 21%; p = 0.999). Ventilator days were significantly lower in responders (10 vs 16; p < 0.001). Competing risk regression (competing risk of death) confirmed association between inhaled nitric oxide response and successful extubation (subdistribution hazard ratio = 2.11; 95% CI, 1.41-3.17; p < 0.001). Response to inhaled nitric oxide was associated with decreased utilization of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation and lower hospital charges (difference in medians of $424,000)., Conclusions: Positive response to inhaled nitric oxide was associated with fewer ventilator days, without change in mortality, potentially via reduced use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. Future studies of inhaled nitric oxide for pediatric acute respiratory distress syndrome should stratify based on oxygenation response, given the association with favorable outcomes.

Objectives: Both oxygenation and peak inspiratory pressure are associated with mortality in pediatric acute respiratory distress syndrome. Since oxygenation and respiratory mechanics are linked, it is difficult to identify which variables, pressure or oxygenation, are independently associated with outcome. We aimed to determine whether respiratory mechanics (peak inspiratory pressure, positive end-expiratory pressure, ΔP [PIP minus PEEP], tidal volume, dynamic compliance [Cdyn]) or oxygenation (PaO2/FIO2) was associated with mortality., Design: Prospective, observational, cohort study., Setting: University affiliated PICU., Patients: Mechanically ventilated children with acute respiratory distress syndrome (Berlin)., Interventions: None., Measurements and Main Results: Peak inspiratory pressure, positive end-expiratory pressure, ΔP, tidal volume, Cdyn, and PaO2/FIO2 were collected at acute respiratory distress syndrome onset and at 24 hours in 352 children between 2011 and 2016. At acute respiratory distress syndrome onset, neither mechanical variables nor PaO2/FIO2 were associated with mortality. At 24 hours, peak inspiratory pressure, positive end-expiratory pressure, ΔP were higher, and Cdyn and PaO2/FIO2 lower, in nonsurvivors. In multivariable logistic regression, PaO2/FIO2 at 24 hours and ΔPaO2/FIO2 (change in PaO2/FIO2 over the first 24 hr) were associated with mortality, whereas pressure variables were not. Both oxygenation and pressure variables were associated with duration of ventilation in multivariable competing risk regression., Conclusions: Improvements in oxygenation, but not in respiratory mechanics, were associated with lower mortality in pediatric acute respiratory distress syndrome. Future trials of mechanical ventilation in children should focus on oxygenation (higher PaO2/FIO2) rather than lower peak inspiratory pressure or ΔP, as oxygenation was more consistently associated with outcome.