Pediatric Acute Lung Injury Research Articles

Self-Reported Management of IV Fluids and Fluid Accumulation in Children With Acute Respiratory Failure.

Observational studies have shown that fluid overload is independently associated with increased morbidity in critically ill children, especially with respiratory pathology. It is unknown if recent evidence has influenced clinical practice. We sought to describe current IV fluid management in pediatric acute respiratory distress syndrome. Multinational, cross-sectional electronic survey. Pediatric Acute Lung Injury and Sepsis Investigators Network. Pediatric intensivists. None. One-hundred fifty-four respondents (43% response rate) had a median 10 years of experience (Q1-Q3, 4-17.8), in ICUs with a median 24 beds (18-36), where 86% provided extracorporeal membrane oxygenation. For maintenance IV fluid, 96% used the "4-2-1" rule to determine rate, and 59% used dextrose with normal saline for content. For fluid resuscitation, 77% use normal saline in 10 milliliters per kilogram aliquots (42%) or as fluid challenges (37%). Less than 20% of respondents reported resuscitating with 20 mL/kg boluses. Documented intake over output is the favored vital sign to assess (75% vs 57%) and guide fluid management (97% vs 14%) over central venous pressure. The majority of respondents chose 10% fluid overload as the threshold to act in children with pediatric acute respiratory distress syndrome. The majority (77%) agreed that fluid accumulation contributes to worse outcomes in pediatric acute respiratory distress syndrome and should be treated. Ninety-one percent reported conservative fluid management in pediatric acute respiratory distress syndrome is likely to be beneficial or protective. Pediatric intensivists agree that acting on 10% fluid overload in children with pediatric acute respiratory distress syndrome is important. Decisions are being made largely using intake and output documentation, not central venous pressure. These findings are important for future pediatric acute respiratory distress syndrome interventional trials.

Differences Between Pulmonary and Extrapulmonary Pediatric Acute Respiratory Distress Syndrome: A Multicenter Analysis.

Extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome are poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome. This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality. Ten multidisciplinary PICUs in Asia. Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015. None. Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]). Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.

The Pediatric Critical Care Transfusion and Anemia Expertise Initiative Consensus Conference Methodology.

This article describes the methodology used for Pediatric Critical Care Transfusion and Anemia Expertise Initiative Consensus Conference. Consensus conference of international experts in pediatric critical care and transfusion medicine, following standards set by the Institute of Medicine, using the Research and Development/UCLA Appropriateness Method, modeled after the Pediatric Acute Lung Injury Consensus Conference. Topics related to RBC transfusion in children with or at risk for critical illness were divided into nine subgroups with a systematic review of the literature. The panel of 38 content and four methodology experts met three times over the course of 2 years and collaborated to develop evidence-based and, when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children or those at risk for critical illness. Electronic searches were conducted using PubMed, Embase, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. We used a standardized data extraction form to construct evidence tables and graded the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. The consensus conference resulted in 102 recommendation statements, of which 57 were clinical (20 evidence based and 37 based on expert consensus) and 45 detailed recommendations for future research. Dissemination was done via decision tree, a primary publication listing all statements, and separate publications for each subtopic that include supporting arguments for each recommendation. A consensus conference of experts from around the world developed recommendations for RBC transfusions in critically ill children or children at risk for critical illness, the identification of current research gaps, and future research priorities.

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice

Pediatric acute lung injury, usually because of pneumonia, has a mortality rate of more than 20% and an incidence that rivals that of all childhood cancers combined. CD4+ T-cells coordinate the immune response to pneumonia but fail to function robustly among the very young, who have poor outcomes from lung infection. We hypothesized that DNA methylation represses a mature CD4+ T-cell transcriptional program in neonates with pneumonia. Here, we found that neonatal mice (3-4 days old) aspirated with Escherichia coli bacteria had a higher mortality rate than juvenile mice (11-14 days old). Transcriptional profiling with an unsupervised RNA-Seq approach revealed that neonates displayed an attenuated lung CD4+ T-cell transcriptional response to pneumonia compared with juveniles. Unlike neonates, juveniles up-regulated a robust set of canonical T-cell immune response genes. DNA methylation profiling with modified reduced representation bisulfite sequencing revealed 44,119 differentially methylated CpGs, which preferentially clustered around transcriptional start sites and CpG islands. A methylation difference-filtering algorithm detected genes with a high likelihood of differential promoter methylation regulating their expression; these 731 loci encoded important immune response and tissue-protective T-cell pathway components. Disruption of DNA methylation with the hypomethylating agent decitabine induced plasticity in the lung CD4+ T-cell marker phenotype. Altogether, multidimensional profiling suggested that DNA methylation within the promoters of a core set of CD4+ T-cell pathway genes contributes to the hyporesponsive neonatal immune response to pneumonia. These findings also suggest that DNA methylation could serve as a mechanistic target for disease-modifying therapies in pediatric lung infection and injury.

Abstract P-595: IMPLEMENTATION OF RECLASSIFICATION AT 24 HOURS AFTER THE DIAGNOSIS OF ACUTE RESPIRATORY DISTRESS SYNDROME IN CHILDREN

Aims & Objectives: Definition of pediatric acute respiratory distress syndrome (PARDS) is a pragmatic snippet based on the degree of hypoxia at the time of its onset. We aimed to determine whether reclassification by PARDS definition 24 hours after meeting PARDS criteria could have better prognostic ability for risk stratification. Methods A total of 1,101 children who admitted to the intensive care unit (ICU) at Severance hospital were screened. And 283 patients diagnosed as PARDS according to the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition were retrospectively analyzed. Reclassification based on data measured at 24 hours after diagnosis were compared with the initial classification. Primary outcome was in-hospital mortality. Results Overall mortality rate of PARDS in ICU was 36.1%. Multivariate analysis revealed that the risk for mortality was significantly increased according to severity stratification based on metrics collected at 24 hours after the diagnosis (HR [95%CI], 4.809 [2.821–8.197]) for severe PARDS. And mortality risk increased for severe PARDS (2.279 [1.414–3.672]) using the initial classification. Oxygenation index (OI) at the time of diagnosis and at 24 hours after onset showed associations with mortality (aOR [95%CI], 1.042 [1.026–1.058] for initial OI; 1.073 [1.056–1.091] for OI at 24 hours after diagnosis). Change in OI over the first 24 hours were also associated with mortality (1.047 [1.019–1.076]). Conclusions Improvements in oxygenation over the first 24 hours were associated with lower mortality. Implementation of reclassification based on oxygenation metrics 24 hours after the initial diagnosis of PARDS seems valid and may contribute to more individualized treatment in PARDS.

Re-recognition of infectious acute respiratory distress syndrome

From 1903, when Ophuls elaborated infectious pulmonary edema pathologically for the first time, till to 2015, acute respiratory distress syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference was defined by Pediatric Acute Lung Injury Consensus Conference(PALICC), the development of infectious pulmonary edema experienced more than 110 years.In order to improve the re-recognition of infectious pulmonary edema, infectious acute respiratory distress syndrome was expounded on the infectious pathogeny, infection sites, risk factors, diagnosis and treatment in this review. Key words: Infection; Pulmonary edema; Acute respiratory distress syndrome,

Comparison of Prevalence and Outcomes of Pediatric Acute Respiratory Distress Syndrome Using Pediatric Acute Lung Injury Consensus Conference Criteria and Berlin Definition

Our objective was to compare the prevalence and outcomes of pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria and Berlin definitions. We screened case records of all children aged 1 month to 17 years of age admitted to the Pediatric Intensive Care Unit (PICU) over a 3-year period (2015-2017) for presence of any respiratory difficulty at admission or during PICU stay. We applied both PALICC and Berlin criteria to these patients. Data collection included definition and outcome related variables. Data were compared between the "PALICC only group" and the "Berlin with or without PALICC" group using Stata 11. Of a total of 615 admissions, 246 were identified as having respiratory difficulty at admission or during PICU stay. A total of 61 children (prevalence 9.9%; 95% CI: 7.8-12.4) fulfilled the definition of acute respiratory distress syndrome (ARDS) with either of the two criteria. While 60 children (98%) fulfilled PALICC criteria, only 26 children (43%) fulfilled Berlin definition. There was moderate agreement between the two definitions (Kappa: 0.51; 95% CI: 0.40-0.62; observed agreement 85%). Greater proportion of patients had severe ARDS in the "Berlin with or without PALICC group" as compared to the "PALICC only" group (50 vs. 19%). There was no difference between the groups with regard to key clinical outcomes such as duration of ventilation (7 vs. 8 days) or mortality [51.4 vs. 57.7%: RR (95% CI): 0.99 (0.64-1.5)]. In comparison to Berlin definition, the PALICC criteria identified more number of patients with ARDS. Proportion with severe ARDS and complications was greater in the "Berlin with or without PALICC" group as compared to the "PALICC only" group. There were no differences in clinical outcomes between the groups.

Inflammatory Monocytes Drive Influenza A Virus-Mediated Lung Injury in Juvenile Mice.

Healthy children are more likely to die of influenza A virus (IAV) infection than healthy adults. However, little is known about the mechanisms underlying the impact of young age on the development of life-threatening IAV infection. We report increased mortality in juvenile mice compared with adult mice at each infectious dose of IAV. Juvenile mice had sustained elevation of type I IFNs and persistent NLRP3 inflammasome activation in the lungs, both of which were independent of viral titer. Juvenile mice, but not adult mice, had increased MCP-1 levels that remained high even after viral clearance. Importantly, continued production of MCP-1 was associated with persistent recruitment of monocytes to the lungs and prolonged elevation of inflammatory cytokines. Transcriptional signatures of recruited monocytes to the juvenile and adult IAV-infected lungs were assessed by RNA-seq. Genes associated with a proinflammatory signature were upregulated in the juvenile monocytes compared with adult monocytes. Depletion of monocytes with anti-CCR2 Ab decreased type I IFN secretion, NLRP3 inflammasome activation, and lung injury in juvenile mice. This suggests an exaggerated inflammatory response mediated by increased recruitment of monocytes to the lung, and not an inability to control viral replication, is responsible for severe IAV infection in juvenile mice. This study provides insight into severe IAV infection in juveniles and identifies key inflammatory monocytes that may be central to pediatric acute lung injury secondary to IAV.

Face and content validity of variables associated with the difficult-to-sedate child in the paediatric intensive care unit: A survey of paediatric critical care clinicians

BackgroundClinicians recognise that some critically ill children are difficult-to-sedate. It may be possible to identify this clinical phenotype for sedation response using statistical modelling techniques adopted from machine learning. This requires identification of a finite number of variables to include in the statistical model. ObjectiveTo establish face and content validity for 17 candidate variables identified in the international literature as characteristic of the difficult-to-sedate child phenotype. MethodsPaediatric critical care clinicians rated the relevance of 17 variables characterising the difficult-to-sedate child using a four-point scale ranging from not (1) to highly relevant (4). Face and content validity of these variables were assessed by calculating a mean score for each item and computing an item-level content validity index. Items with a mean score >1 were rated as having adequate face validity. An item-level content validity index ≥0.70 indicated good to excellent content validity. Setting and participantsWeb-based survey emailed to members of the Pediatric Acute Lung Injury and Sepsis Investigators Network or the Society of Critical Care Medicine Pediatric Sedation Study Group. ResultsOf 411 possible respondents, 121 useable surveys were returned for a response rate of 29%. All items had a mean score >1, indicating adequate face validity. Ten of 17 items scored an item-level content validity index ≥0.70. The highest scoring items were requiring three or more sedation classes simultaneously, daily modal sedation score indicating agitation, sedation score indicating agitation for 2 consecutive hours, receiving sedatives at a dose >90th percentile of the usual starting dose, and receiving intermittent paralytic doses for sedation. ConclusionsComputation of an item-level content validity index validated variables to include in statistical modelling of the difficult-to-sedate phenotype. The results indicate consensus among paediatric critical care clinicians that the majority of candidate variables identified through literature review are characteristic of the difficult-to-sedate child.

RBC Transfusions Are Associated With Prolonged Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome*

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. Retrospective analysis of prospectively enrolled cohort. Large, academic PICU. 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. 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. 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. 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.

Practice Variation in the Immediate Postoperative Care of Pediatric Kidney Transplantation: A National Survey

IntroductionAdvances in organ allocation, surgical technique, immunosuppression, and long-term follow-up have led to a significant improvement in kidney transplant outcomes. Although there are clear recommendations for several aspects of kidney transplant management, there are no pediatric-specific guidelines for immediate postoperative care. The aim of this survey is to examine practice variations in the immediate postoperative care of pediatric kidney transplant patients. MethodsWe surveyed medical directors of Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)-affiliated pediatric intensive care units regarding center-specific immediate postoperative management of pediatric kidney transplantation. ResultsThe majority of PALISI centers admit patients to the pediatric intensive care unit postoperatively, and 97% of the centers involve a pediatric nephrologist in immediate postoperative care. Most patients undergo invasive hemodynamic monitoring; 97% of centers monitor invasive arterial blood pressure and 88% monitor central venous pressure. Most centers monitor serum electrolytes every 4 to 6 hours. Wide variation exists regarding blood pressure goal, fluid replacement type, frequency of obtaining kidney ultrasound, and use of prophylactic anticoagulation. ConclusionThere is consistent practice across PALISI centers in regards to many aspects of immediate postoperative management of pediatric kidney transplantation. However, variation still exists in some management aspects that warrant further discussions to reach a national consensus.

Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A Multicenter Observational Study.

The Pediatric Acute Lung Injury Consensus Conference developed a pediatric specific definition for acute respiratory distress syndrome (PARDS). In this definition, severity of lung disease is stratified into mild, moderate, and severe groups. We aim to describe the epidemiology of patients with PARDS across Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference risk stratification accurately predicts outcome in PARDS. A multicenter, retrospective, descriptive cohort study. Ten multidisciplinary PICUs in Asia. All mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for PARDS between 2009 and 2015. None. Data on epidemiology, ventilation, adjunct therapies, and clinical outcomes were collected. Patients were followed for 100 days post diagnosis of PARDS. A total of 373 patients were included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild, moderate, and severe PARDS, respectively. The most common risk factor for PARDS was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16 [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate, and severe, respectively). Overall PICU mortality for PARDS was 113 of 373 (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site, presence of comorbidities and severity of illness in the multivariate Cox proportional hazard regression model, patients with moderate (hazard ratio, 1.88 [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI, 1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with mild PARDS. Mortality from PARDS is high in Asia. The Pediatric Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for risk stratification.

A retrospective analysis of the factors related to pediatric acute respiratory distress syndrome′s prognosis

Objective To investigate the prognostic factors of pediatric acute respiratory distress syndrome(pARDS), according to pARDS criteria from the 2015 Pediatric Acute Lung Injury Consensus Conference. Methods Clinical data of 69 cases with pARDS in PICU of Beijing Children′s Hospital affiliated to Capital Medical University from January 2009 to December 2015 were retrospectively analyzed. Results Among the 69 cases of pARDS, there were 13 cases with mild ARDS, 19 cases with moderate ARDS and 37 cases with severe ARDS.Seventeen pARDS were dead in PICU, including 2 mild pARDS, 3 moderate pARDS and 12 severe pARDS, and 14 pARDS of them were female, 3 pARDS were male.Gender and chronic complication were related to the outcomes of pARDS, and the difference was significant(P<0.05). The mortality of pARDS with chronic complication was up to 69.23%.Duration of mechanical ventilation was related to PICU hospital stay and total length of hospital stay (correlation: 0.324, 0.181, P<0.01). Duration of mechanical ventilation was also related to weight(correlation 0.491, P<0.01), and weight was a protective factor. Conclusion pARDS is one of the most critical diseases in PICU with low morbidity and high mortality, the mortality of pARDS in this study is 24.64%.Female or chronic co-morbidities pARDS may have poor prognosis.Duration of mechanical ventilation determines the PICU length of stay and total hospital length of stay, and weight is the protective factor of the duration of mechanical ventilation. Key words: Acute respiratory distress syndrome; Children; Prognosis

Recent Advances in Pediatric Acute Respiratory Distress Syndrome (PARDS)

The purpose of this review is to summarize the recent literature on pediatric acute respiratory distress syndrome (PARDS). This review will focus on, but not be limited to, literature using the recent definition of PARDS established by the Pediatric Acute Lung Injury Consensus Conference (PALICC) group in 2015. Mortality rates for PARDS have recently decreased to 10–15%. Clinical trials in PARDS have (1) emphasized the relative importance of early oxygenation in predicting mortality; (2) suggested a role for protocolized sedation in patients managed with extracorporeal membrane oxygenation (ECMO); (3) found no mortality benefit to high-frequency oscillatory ventilation (HFOV), exogenous surfactant, or corticosteroids; and (4) suggested biomarkers and whole exome sequencing as methods for personalizing management. Recent laboratory studies have suggested differences in responsiveness to high tidal volume injury in juvenile rodents. The near future of PARDS management could include earlier risk stratification of patients by (1) oxygenation within 24 h of PARDS diagnosis and (2) use of biomarkers and subphenotypes. Despite challenges in performing clinical trials in children, the PALICC definition presents an opportunity to explore these and more research questions in PARDS separately from adult cohorts.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents, Part 3: Focus on Cardiorespiratory Dysfunction, Infections, Liver Dysfunction, and Delirium

Some patients with veno-occlusive disease (VOD) have multiorgan dysfunction, and multiple teams are involved in their daily care in the pediatric intensive care unit. Cardiorespiratory dysfunction is critical in these patients, requiring immediate action. The decision of whether to use a noninvasive or an invasive ventilation strategy may be difficult in the setting of mucositis or other comorbidities in patients with VOD. Similarly, monitoring of organ functions may be very challenging in these patients, who may have fulminant hepatic failure with or without hepatic encephalopathy complicated by delirium and/or infections. In this final guideline of our series on supportive care in patients with VOD, we address some of these questions and provide evidence-based recommendations on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2—Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues

Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provide standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. We consider the available evidence using the GRADE criteria.

Pediatric ARDS.

The Pediatric Acute Lung Injury Consensus Conference (PALICC) has provided the critical care community with the first pediatric-focused definition for ARDS. The PALICC recommendations provide guidance on conventional ventilator management, gas exchange goals, use of high-frequency ventilation, adjunct management approaches, and the application of extracorporeal membrane oxygenation for pediatric ARDS (PARDS). Although outcomes for PARDS have improved over the past decade, mortality and morbidity remain significant. Pediatric-specific criteria may provide the ability to more promptly recognize and diagnose PARDS in clinical practice. Improvements in prognostication and stratification of disease severity may help to guide therapeutic interventions. Improved comparisons between patients and studies may help to promote future clinical investigations. Hopefully, the recommendations provided by PALICC, in terms of defining and managing ARDS, will stimulate additional research to better guide therapy and further improve outcomes for critically ill infants and children with ARDS.

Extracorporeal Membrane Oxygenation for Severe Pediatric Respiratory Failure.

Extracorporeal membrane oxygenation (ECMO) was developed initially in the 1960s to support refractory respiratory failure in addition to the cardiac support inherent in a venoarterial bypass circuit. Early successes occurred predominantly in the neonatal population with subsequent randomized controlled trials and comprehensive reviews concluding therapeutic efficacy for ECMO in neonatal respiratory failure. In contrast, the evidence supporting ECMO for respiratory failure in children is less definitive. However, although pediatric randomized controlled trials have not been completed, sufficient evidence in support of ECMO as a beneficial therapy for pediatric respiratory failure exists. The acceptance of clinical utility and benefit from ECMO for pediatric ARDS and the trend toward increasing venovenous ECMO use have led to its inclusion in the Pediatric Acute Lung Injury Consensus Conference as a strongly agreed upon recommendation for severe pediatric ARDS. However, the Pediatric Acute Lung Injury Consensus Conference recommendations supporting the use of ECMO for pediatric ARDS highlight the lack of evidence-based selection criteria when determining ECMO candidacy in pediatric patients with ARDS. Ultimately, decisions to proceed with ECMO and the concomitant risk of potential life-threatening complications must consider multiple factors that balance potential risks and likelihood of benefit, pre-morbid conditions and impact on potential post-ECMO quality of life, candidacy for lung transplantation, and patient and family goals of care. This review will discuss ECMO for the support of pediatric respiratory failure, ventilator management during ECMO, considerations impacting timing of decannulation, and developing techniques.

Surfactants in Acute Respiratory Distress Syndrome in Infants and Children: Past, Present and Future.

There is a lack of definitive data on the effective management of acute respiratory distress syndrome (ARDS) in infants and children. The development and validation of the Berlin definition (BD) for ARDS and the Pediatric Acute Lung Injury Consensus Conference (PALICC) recommendations in children represented a major advance in optimizing research and treatment, mainly due to the introduction of a severe ARDS category. Proposed reasons for the lack of consistent results with surfactants in children and infants compared with neonates include different causes, type of lung damage (direct or indirect), timing and mode of administration as well as the type of surfactant used. Secretory phospholipase A2 plays an important role in inflammation and possible dysfunction of surfactants in ARDS. Bronchoalveolar lavage (BAL) with normal saline and surfactant allows the removal of inhaled material, the recruitment of non-ventilating areas and the maintenance of the surfactant pool size. BAL with diluted surfactant allows rapid absorption of the surfactant at the air/liquid interface, which blocks the progression of pathological lung disease and in turn disrupts the inflammatory cycle. Importantly, it is now recognized that the type of surfactant, the time of administration and the method of administration could all play an important role in the management of ARDS, and there is evidence that surfactant is effective and well tolerated in children and infants with ARDS.

Pediatric Acute Respiratory Distress Syndrome in Pediatric Allogeneic Hematopoietic Stem Cell Transplants: A Multicenter Study.

Immunodeficiency is both a preexisting condition and a risk factor for mortality in pediatric acute respiratory distress syndrome. We describe a series of pediatric allogeneic hematopoietic stem cell transplant patients with pediatric acute respiratory distress syndrome based on the recent Pediatric Acute Lung Injury Consensus Conference guidelines with the objective to better define survival of this population. Secondary analysis of a retrospective database. Twelve U.S. pediatric centers. Pediatric allogeneic hematopoietic stem cell transplant recipients requiring mechanical ventilation. None. During the first week of mechanical ventilation, patients were categorized as: no pediatric acute respiratory distress syndrome or mild, moderate, or severe pediatric acute respiratory distress syndrome based on oxygenation index or oxygen saturation index. Univariable logistic regression evaluated the association between pediatric acute respiratory distress syndrome and PICU mortality. A total of 91.5% of the 211 patients met criteria for pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition: 61.1% were severe, 27.5% moderate, and 11.4% mild. Overall survival was 39.3%. Survival decreased with worsening pediatric acute respiratory distress syndrome: no pediatric acute respiratory distress syndrome 66.7%, mild 63.6%, odds ratio = 1.1 (95% CI, 0.3-4.2; p = 0.84), moderate 52.8%, odds ratio = 1.8 (95% CI, 0.6-5.5; p = 0.31), and severe 24.6%, odds ratio = 6.1 (95% CI, 2.1-17.8; p < 0.001). Nonsurvivors were more likely to have multiple consecutive days at moderate and severe pediatric acute respiratory distress syndrome (p < 0.001). Moderate and severe patients had longer PICU length of stay (p = 0.01) and longer mechanical ventilation course (p = 0.02) when compared with those with mild or no pediatric acute respiratory distress syndrome. Nonsurvivors had a higher median maximum oxygenation index than survivors at 28.6 (interquartile range, 15.5-49.9) versus 15.0 (interquartile range, 8.4-29.6) (p < 0.0001). In this multicenter cohort, the majority of pediatric allogeneic hematopoietic stem cell transplant patients with respiratory failure met oxygenation criteria for pediatric acute respiratory distress syndrome based on the Pediatric Acute Lung Injury Consensus Conference definition within the first week of invasive mechanical ventilation. Length of invasive mechanical ventilation, length of PICU stay, and mortality increased as the severity of pediatric acute respiratory distress syndrome worsened.