Priorities for Clinical Research in Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From the Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: The management of bleeding and thrombotic complications of ECMO. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.

Protocol for the Prone and Oscillation Pediatric Clinical Trial (PROSpect).

OBJECTIVES: Respiratory management for pediatric acute respiratory distress syndrome (PARDS) remains largely supportive without data to support one approach over another, including supine versus prone positioning (PP) and conventional mechanical ventilation (CMV) versus high-frequency oscillatory ventilation (HFOV). DESIGN: We present the research methodology of a global, multicenter, two-by-two factorial, response-adaptive, randomized controlled trial of supine versus PP and CMV versus HFOV in high moderate-severe PARDS, the Prone and Oscillation Pediatric Clinical Trial (PROSpect, www.ClinicalTrials.gov, NCT03896763). SETTING: Approximately 60 PICUs with on-site extracorporeal membrane oxygenation support in North and South America, Europe, Asia, and Oceania with experience using PP and HFOV in the care of patients with PARDS. PATIENTS: Eligible pediatric patients (2 wk old or older and younger than 21 yr) are randomized within 48 h of meeting eligibility criteria occurring within 96 h of endotracheal intubation. INTERVENTIONS: One of four arms, including supine/CMV, prone/CMV, supine/HFOV, or prone/HFOV. We hypothesize that children with high moderate-severe PARDS treated with PP or HFOV will demonstrate greater than or equal to 2 additional ventilator-free days (VFD). MEASUREMENTS AND MAIN RESULTS: The primary outcome is VFD through day 28; nonsurvivors receive zero VFD. Secondary and exploratory outcomes include nonpulmonary organ failure-free days, interaction effects of PP with HFOV on VFD, 90-day in-hospital mortality, and among survivors, duration of mechanical ventilation, PICU and hospital length of stay, and post-PICU functional status and health-related quality of life. Up to 600 patients will be randomized, stratified by age group and direct/indirect lung injury. Adaptive randomization will first occur 28 days after 300 patients are randomized and every 100 patients thereafter. At these randomization updates, new allocation probabilities will be computed based on intention-to-treat trial results, increasing allocation to well-performing arms and decreasing allocation to poorly performing arms. Data will be analyzed per intention-to-treat for the primary analyses and per-protocol for primary, secondary, and exploratory analyses. CONCLUSIONS: PROSpect will provide clinicians with data to inform the practice of PP and HFOV in PARDS.

Obesity and Extracorporeal Membrane Oxygenation.

Obesity is increasing in prevalence worldwide and carries a theoretical increased risk of morbidity and mortality in critical illness, including hypercoagulability, thrombosis, and renal dysfunction. Obesity has historically been considered a relative contraindication to candidacy for extracorporeal membrane oxygenation (ECMO); however, recent research has suggested that obesity may be associated with improved outcomes in ECMO. This review was conducted to assess and synthesize the existing literature on ECMO outcomes in the obese population. We searched PubMed, Scopus, and CENTRAL databases for obesity and ECMO outcomes, and articles were screened independently by 2 authors. The selection process yielded 29 articles, with one ambispective and 28 retrospective cohort studies. Analyses of these studies show no evidence of globally increased mortality or complications in obesity. Prospective evaluation is needed to further investigate this relationship, but there is currently no evidence to support using body mass index as exclusionary criteria for ECMO.

Challenges of Nutrition Support in Pediatric Patients Requiring Extracorporeal Membrane Oxygenation.

Nutrition support in critically ill infants and children remains an integral part of providing optimal care for these patients. The pediatric patient requiring extracorporeal membrane oxygenation therapy faces specific challenges to the provision of suitable nutrition support. In this review, we aimed to summarize the existing literature around some of the more challenging aspects of delivering appropriate nutrition to children receiving extracorporeal membrane oxygenation.

Optimization of the IntraVascular Oxygenator Catheter Using Angular Oscillation.

We demonstrate a methodology which both improves oxygen transport and reduces or eliminates bubble formation in a novel hyperbaric membrane oxygenator catheter model system. Angular oscillations were introduced to a bundle of hollow fiber membranes (HFMs) supplied with hyperbaric 100% oxygen at average gauge pressures up to 0.35 barg. Oscillating bundles enabled delivery of an oxygen flux of up to 400 mL min-1 m-2 in an aqueous solution, a doubling over a previous non-oscillating setup. Similarly, the addition of angular oscillations facilitated a five-fold reduction in pressure to achieve similar oxygen flux. The increased angular speed of oscillation improved flux, while the addition of angular micro-oscillation variations resulted in flux reductions of 7-20% compared to continuous macro-oscillation only, depending on mixing conditions. However, semi-quantitative visual observation demonstrated that angular oscillations reduced or eliminated the instance of oxygen bubble formation on the HFMs. The modeled mass transfer coefficients indicated a quasi linear relationship between rotational velocity and flux, suggesting that faster oscillation speeds could further improve oxygen mass transport allowing for HFM bundles to maintain high oxygen fluxes while eliminating bubble formation. This encourages further development of our compact oxygenating catheter that could be used intravascularly.

Mechanical ventilation during pediatric extracorporeal life support.

PURPOSE OF REVIEW: To discuss the role of ventilator induced lung injury (VILI) and patient self-inflicted lung injury in ventilated children supported on extracorporeal membrane oxygenation (ECMO). RECENT FINDINGS: While extracorporeal life support is used routinely used every day around the globe to support neonatal, pediatric, and adult patients with refractory cardiac and/or respiratory failure, the optimal approach to mechanical ventilation, especially for those with acute respiratory distress syndrome (ARDS), remains unknown and controversial. Given the lack of definitive data in this population, one must rely on available evidence in those with ARDS not supported with ECMO and extrapolate adult observations. Ventilatory management should include, as a minimum standard, limiting inspiratory and driving pressures, providing a sufficient level of positive end-expiratory pressure, and setting a low rate to reduce mechanical power. Allowing for spontaneous breathing and use of pulmonary specific ancillary treatment modalities must be individualized, while balancing the risk and benefits. Future studies delineating the best strategies for optimizing MV during pediatric extracorporeal life support are much needed. SUMMARY: Future investigations will hopefully provide the needed evidence and better understanding of the overall goal of reducing mechanical ventilation intensity to decrease risk for VILI and promote lung recovery for those supported with ECMO.

Update on percutaneous and perventricular device closure of congenital ventricular septal defect.

INTRODUCTION: Ventricular septal defect is the most common congenital heart defect. Surgical repair has been standard therapy for symptomatic ventricular septal defects since the 1950s. Catheter-based device closure of ventricular septal defects emerged in the 1980s and has become a safe and effective alternative in select patients. AREAS COVERED: This review focuses on patient selection and procedural techniques for device closure of ventricular septal defects, including percutaneous and hybrid perventricular approaches. The available devices used for these procedures and outcomes of their use are reviewed. EXPERT OPINION: Percutaneous and perventricular device closure of ventricular septal defects is safe and effective in select patients. However, the majority of ventricular septal defects requiring closure continue to be managed with conventional surgery. Further development and investigation of transcatheter and hybrid surgical approaches for closing ventricular septal defects is required.

Hemodynamic Effects of a High-Frequency Oscillatory Ventilation Open-Lung Strategy in Critically Ill Children With Acquired or Congenital Cardiac Disease.

OBJECTIVES: To study the hemodynamic consequences of an open-lung high-frequency oscillatory ventilation (HFOV) strategy in patients with an underlying cardiac anomaly with or without intracardiac shunt or primary pulmonary hypertension with severe lung injury. DESIGN: Secondary analysis of prospectively collected data. SETTING: Medical-surgical PICU. PATIENTS: Children less than 18 years old with cardiac anomalies (± intracardiac shunt) or primary pulmonary hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 52 subjects were analyzed, of whom 39 of 52 with cardiac anomaly (23/39 with intracardiac shunt) and 13 of 52 with primary pulmonary hypertension. Fourteen patients were admitted postoperatively, and 26 patients were admitted with acute respiratory failure. Five subjects (9.6%) were canulated for ECMO (of whom four for worsening respiratory status). Ten patients (19.2%) died during PICU stay. Median conventional mechanical ventilation settings prior to HFOV were peak inspiratory pressure 30 cm H 2 O (27-33 cm H 2 O), positive end-expiratory pressure 8 cm H 2 O (6-10 cm H 2 O), and F io2 0.72 (0.56-0.94). After transitioning to HFOV, there was no negative effect on mean arterial blood pressure, central venous pressure, or arterial lactate. Heart rate decreased significantly over time ( p < 0.0001), without group differences. The percentage of subjects receiving a fluid bolus decreased over time ( p = 0.003), especially in those with primary pulmonary hypertension ( p = 0.0155) and without intracardiac shunt ( p = 0.0328). There were no significant differences in the cumulative number of daily boluses over time. Vasoactive Infusion Score did not increase over time. Pa co2 decreased ( p < 0.0002) and arterial pH significantly improved ( p < 0.0001) over time in the whole cohort. Neuromuscular blocking agents were used in all subjects switched to HFOV. Daily cumulative sedative doses were unchanged, and no clinically apparent barotrauma was found. CONCLUSIONS: No negative hemodynamic consequences occurred with an individualized, physiology-based open-lung HFOV approach in patients with cardiac anomalies or primary pulmonary hypertension suffering from severe lung injury.

Nutritional Support in Children Meeting the At-Risk for Pediatric Acute Respiratory Distress Syndrome Criteria.

Pediatric acute respiratory distress syndrome (PARDS) is a prevalent condition in the PICU with a high morbidity and mortality, but effective preventative strategies are lacking. OBJECTIVES: To examine associations between early enteral nutrition (EN) and PICU outcomes in a cohort of children meeting the 2015 Pediatric Acute Lung Injury Consensus Conference "at-risk" for pediatric acute respiratory distress syndrome (ARF-PARDS) criteria. DESIGN SETTING AND PARTICIPANTS: This was a single-center, electronic health record-based retrospective chart review. We included children less than or equal to 18 years-old admitted to our mixed medical-surgical PICU from January 2017 to December 2018 who met ARF-PARDS criteria within 48 hours of admission. Children were categorized as receiving "early" EN if feeds were initiated within 48 hours of admission. All others were categorized as "delayed" EN. MAIN OUTCOMES AND MEASURES: Extracted data included demographics, illness characteristics including primary diagnosis and Pediatric Risk of Mortality (PRISM) III score, respiratory support and oxygenation indices, nutritional data, and PICU length of stay (LOS). The primary outcome of interest was subsequent diagnosis of PARDS. RESULTS: Of 201 included children, 152 (75.6%) received early EN. The most common admission diagnoses were pneumonia, bronchiolitis, and influenza. Overall, 21.4% (n = 43) of children developed PARDS. Children receiving early EN had a subsequent diagnosis of PARDS less often then children receiving delayed EN (15.1% vs 40.8%; p < 0.001), an association that persisted after adjusting for patient demographics and illness characteristics, including PRISM III and diagnosis (adjusted odds ratio, 0.24; 95% CI, 0.10-0.58; p = 0.002). Early EN was also associated with a shorter PICU LOS in univariate analysis (2.2 d [interquartile range, 1.5-3.4 d] vs 4.2 d [2.7-8.9 d]; p < 0.001). CONCLUSIONS AND RELEVANCE: In this single-center, retrospective cohort study, compared with children with ARF-PARDS who received late EN, those who received early EN demonstrated a reduced odds of subsequent diagnosis of PARDS, and an unadjusted reduction in PICU LOS when compared with delayed EN. Prospective studies should be designed to confirm these findings.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Invasive Ventilatory Support in Patients With Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: To provide evidence for the Second Pediatric Acute Lung Injury Consensus Conference updated recommendations and consensus statements for clinical practice and future research on invasive mechanical ventilation support of patients with pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included clinical studies of critically ill patients undergoing invasive mechanical ventilation for PARDS, January 2013 to April 2022. In addition, meta-analyses and systematic reviews focused on the adult acute respiratory distress syndrome population were included to explore new relevant concepts (e.g., mechanical power, driving pressure, etc.) still underrepresented in the contemporary pediatric literature. DATA EXTRACTION: Title/abstract review, full text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations, good practice statements and research statements. We identified 26 pediatric studies for inclusion and 36 meta-analyses or systematic reviews in adults. We generated 12 recommendations, two research statements, and five good practice statements related to modes of ventilation, tidal volume, ventilation pressures, lung-protective ventilation bundles, driving pressure, mechanical power, recruitment maneuvers, prone positioning, and high-frequency ventilation. Only one recommendation, related to use of positive end-expiratory pressure, is classified as strong, with moderate certainty of evidence. CONCLUSIONS: Limited pediatric data exist to make definitive recommendations for the management of invasive mechanical ventilation for patients with PARDS. Ongoing research is needed to better understand how to guide best practices and improve outcomes for patients with PARDS requiring invasive mechanical ventilation.

Cardiovascular effects of COVID-19 in children.

Introduction: Although severe acute respiratory failure is the primary cause of morbidity and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this viral infection leads to cardiovascular disease in some individuals. Cardiac effects of the virus include myocarditis, pericarditis, arrhythmias, coronary aneurysms and cardiomyopathy, and can result in cardiogenic shock and multisystem organ failure. Method: This review summarises cardiac manifesta-tions of SARS-CoV-2 in the paediatric population. We performed a scoping review of cardiovascular disease associated with acute coronavirus disease 2019 (COVID-19) infection, multisystem inflammatory syndrome in children (MIS-C), and mRNA COVID-19 vaccines. Also examined are special considerations for paediatric athletes and return to play following COVID-19 infection. Results: Children presenting with acute COVID-19 should be screened for cardiac dysfunction and a thorough history should be obtained. Further cardiovascular evaluation should be considered following any signs/symptoms of arrhythmias, low cardiac output, and/or myopericarditis. Patients admitted with severe acute COVID-19 should be monitored with continuous cardiac monitoring. Laboratory testing, as clinically indicated, includes tests for troponin and B-type natriuretic peptide or N-terminal pro-brain natriuretic peptide. Echocardiography with strain evaluation and/or cardiac magnetic resonance imaging should be considered to evaluate diastolic and systolic dysfunction, coronary anatomy, the pericardium and the myocardium. For patients with MIS-C, combination therapy with intravenous immunoglobulin and glucocorticoid therapy is safe and potentially disease altering. Treatment of MIS-C targets the hyperimmune response. Supportive care, including mechanical support, is needed in some cases. Conclusion: Cardiovascular disease is a striking feature of SARS-CoV-2 infection. Most infants, children and adolescents with COVID-19 cardiac disease fully recover with no lasting cardiac dysfunction. However, long-term studies and further research are needed to assess cardiovascular risk with variants of SARS-CoV-2 and to understand the pathophysiology of cardiac dysfunction with COVID-19.

Pediatric Acute Lung Injury and Sepsis Investigators (PALISI): Evolution of an Investigator-Initiated Research Network.

The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network originated over 20 years ago to foster research to optimize the care of critically ill infants and children. Over this period, PALISI has seen two major evolutions: formalization of our network infrastructure and a broadening of our clinical research focus. First, the network is unique in that its activities and meetings are funded by subscriptions from members who now comprise a multidisciplinary group of investigators from over 90 PICUs all over the United States (US) and Canada, with collaborations across the globe. In 2020, the network converted into a standalone, nonprofit organizational structure (501c3), making the PALISI Network formally independent of academic and clinical institutions or professional societies. Such an approach allows us to invest in infrastructure and future initiatives with broader opportunities for fund raising. Second, our research investigations have expanded beyond the original focus on sepsis and acute lung injury, to incorporate the whole field of pediatric critical care, for example, efficient liberation from mechanical ventilator support, prudent use of blood products, improved safety of intubation practices, optimal sedation practices and glucose control, and pandemic research on influenza and COVID-19. Our network approach in each field follows, where necessary, the full spectrum of clinical and translational research, including: immunobiology studies for understanding basic pathologic mechanisms; surveys to explore contemporary clinical practice; consensus conferences to establish agreement about literature evidence; observational prevalence and incidence studies to measure scale of a clinical issue or question; case control studies as preliminary best evidence for design of definitive prospective studies; and, randomized controlled trials for informing clinical care. As a research network, PALISI and its related subgroups have published over 350 peer-reviewed publications from 2002 through September 2022.

Current evidence for pharmacologic therapy following stage 1 palliation for single ventricle congenital heart disease.

INTRODUCTION: Infants with single ventricle congenital heart disease are vulnerable to complications between stage 1 and stage 2 of palliation. Pharmaceutical treatment during this period is varied and often dependent on institutional practices as there is little evidence supporting a particular treatment path. AREAS COVERED: This review focuses on medical management of patients following stage I palliation. We performed a scoping review of the current literature regarding angiotensin converting enzyme inhibitors and digoxin treatment in the interstage period. In addition, we discuss other medication classes frequently used in these patients. EXPERT OPINION: Due to significant heterogeneity of anatomy, rarity of disease, and other confounding factors, there is limited evidence to support most commonly used medications within the interstage period. Digoxin is associated with improved mortality within the interstage period and should be considered; however, no large randomized controlled trial exists supporting its use. Prevention of thrombotic complication with aspirin is also associated with improved outcomes and should be considered unless a contraindication exists. The addition of other prescriptions in this patient population should be considered only after an evaluation of the risks and benefits of each medication, recognizing the burden and risk of polypharmacy in this fragile patient population.

Trends in Time to Extubation for Pediatric Postoperative Cardiac Patients and Its Correlation With Changes in Clinical Outcomes: A Virtual PICU Database Study.

OBJECTIVES: Mechanical ventilation is often used in children after cardiac surgery but can impair hemodynamics and cause lung injury. Early extubation may improve ICU length of stay and survival. We aimed to describe trends in early extubation rates and evaluate if centers that more commonly practice early extubation have better severity-adjusted outcomes. DESIGN: Retrospective analysis was performed of admissions in the Virtual Pediatric Systems (VPS, LLC) database from 2009 to 2018. Early extubation was defined as patients extubated in the operating room or within 6 hours of PICU admission. SETTING: PICUs participating in the VPS database. PATIENTS: Children in the VPS database who underwent cardiac surgery. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Among 69,739 subjects, 20% were neonates, 47% underwent early extubation, 5.3% failed extubation, and 2.5% died. Overall, early extubation rates did not change over the study period. Centers were placed in one of four groups based on their early extubation rate in lower complexity surgeries. Centers that most commonly used early extubation had more ICU-free time among all patients in univariable analysis (lowest early extubation group, 23.8 d [interquartile range, 18.2-25.9 d]; highest early extubation group, 24.7 d [20.0-26.2 d]; p < 0.001). After adjusting for center volume, sex, age, surgical complexity, and preoperative ICU admission, increasing center-level early extubation rates were not associated with more ICU-free days. Higher center-level early extubation rate was not associated with mortality in univariable or multivariable analysis but was associated with decreased extubation failure rate (lowest early extubation group, 6.4%; highest early extubation group, 3.6%; p < 0.001). CONCLUSIONS: In this large, multicenter database study, early extubation rates in postoperative cardiac patients did not significantly change between 2009 and 2018. Centers that performed early extubation more frequently did not have shorter ICU stays or difference in mortality rates but did have lower reintubation rates.

Flexible Bronchoscopy in Pediatric Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Pediatric patients with ARDS will on occasion need venovenous extracorporeal membrane oxygenation (VV-ECMO) for organ support. As these patients recover, they may benefit from lung recruitment maneuvers including flexible bronchoscopy (FB). The objective of this study was to assess the clinical course of patients who underwent FB while on VV-ECMO for ARDS. METHODS: This was a secondary analysis of a retrospective multi-center cohort at 10 United States pediatric academic quaternary care centers. Data were collected on 204 subjects age 14 d-18 y on VV-ECMO. RESULTS: 271 FBs were performed on 129 (63%) subjects. Pre-FB tidal volume was 1.8 mL/kg compared to 2.22 mL/kg following FB (P = .007). Dynamic compliance also improved from pre-FB to post-FB (2.23 vs 3.04 mL/cm H2O, P = .005). There was a low incidence of complications following FB (3.1%). Subjects in the FB group had fewer ECMO-free days (EFDs) (17.9 vs 22.1 d, P < .001), fewer ventilator-free days (VFDs) (40.0 vs 46.5 d, P = .001), and longer ICU length of stay (LOS) (18 vs 32 d, P < .001). Subjects in the early versus late FB group had more EFDs (19.4 vs 15.2 d, P = .003), more VFDs (43.0 vs 34.0 d, P = .004), and shorter ICU LOS (27.5 vs 35.5 d, P = .045). Mortality in the subjects who had at least one FB was 27.1% compared to 40% in the subjects who did not have a FB while on VV-ECMO (P = .057). CONCLUSIONS: FB can be performed on patients while anticoagulated on VV-ECMO with a low incidence of complications. FB may be beneficial especially when performed early in the course of VV-ECMO.

Intravascular Gas Exchange: Physiology, Literature Review, and Current Efforts.

Acute respiratory failure with inadequate oxygenation and/or ventilation is a common reason for ICU admission in children and adults. Despite the morbidity and mortality associated with acute respiratory failure, few proven treatment options exist beyond invasive ventilation. Attempts to develop intravascular respiratory assist catheters capable of providing clinically important gas exchange have had limited success. Only one device, the IVOX catheter, was tested in human clinical trials before development was halted without FDA approval. Overcoming the technical challenges associated with providing safe and effective gas exchange within the confines of the intravascular space remains a daunting task for physicians and engineers. It requires a detailed understanding of the fundamentals of gas transport and respiratory physiology to optimize the design for a successful device. This article reviews the potential benefits of such respiratory assist catheters, considerations for device design, previous attempts at intravascular gas exchange, and the motivation for continued development efforts.