Adam S. Himebauch

Objectives: To develop and internally validate a multivariable prediction model for survival to hospital discharge after pediatric extracorporeal cardiopulmonary resuscitation (ECPR) for in-hospital cardiac arrest (IHCA), and to use this model to derive risk-standardized survival rates (RSSRs) and quantify between-hospital variation in outcomes. Design: Retrospective multicenter cohort study. Setting: Hospitals contributing to the Extracorporeal Life Support Organization (ELSO) registry between 2020 and 2023. Patients: Children (< 18 yr) treated with ECPR for IHCA. Interventions: None. Measurements and Main Results: Eligible patients were identified from the ELSO Registry and split into derivation ( N = 1060) and validation ( N = 317) cohorts using a hospital-stratified split to preserve within-hospital clustering. Survival prediction models were derived using penalized logistic regression with the least absolute shrinkage and selection operator. A full-event model incorporating 14 routinely available clinical variables demonstrated fair discrimination (area under the curve, 0.728 in the derivation cohort and 0.678 in the validation cohort) and good calibration (observed-to-expected ratio, 0.995; Brier score, 0.222 in the validation cohort). This model was embedded in a multilevel logistic regression model to generate hospital-level RSSRs for centers reporting five or more ECPR cases. Between-hospital variation was quantified using the median odds ratio, which was 1.30 (95% CI, 1.11–1.93), indicating significant differences in survival likelihood between centers after adjusting for patient-level risk. Conclusions: In a large, international cohort of pediatric ECPR patients, we developed and internally validated a clinically interpretable model for survival to hospital discharge. The model performance as a discriminator likely limits its use as a standalone tool for clinical decision-making. However, strong internal calibration allowed for determination of hospital-level RSSRs, which revealed significant inter-hospital variability. These findings demonstrate the feasibility of developing a risk-adjustment model capable of estimating hospital-level RSSRs. Additional external validation and evaluation of residual case-mix differences are needed before such models can be used for benchmarking across pediatric ECPR centers.

Objective: Fluid overload (FO) after pediatric septic shock resuscitation increases the risk of secondary organ failure and long-term morbidity. We hypothesized that early hemodynamic point-of-care ultrasound (hPOCUS) use in pediatric septic shock would be associated with decreased FO. Methods: Retrospective, observational study between 2015 and 2018 in a large academic Pediatric Intensive Care Unit (PICU) of children < 18 years receiving ≥ 40 mL/kg of bolus fluids or vasoactive infusion for treatment of septic shock. %FO and severe FO (%FO ≥ 15%) at 72 h after shock onset were compared between children with hPOCUS exposure < 6 h after shock onset and those without. %FO was calculated: [(fluid in – out)/weight on PICU admission]*100. The association between hPOCUS < 6 h after septic shock onset and %FO and severe FO were evaluated. Results: Of 591 children included, 115 (19.4%) had hPOCUS within 6 h. Children with early hPOCUS vs. without had higher PIM-3; median 4.3, IQR 2.9–9.4 vs. 3.2, IQR 0.9–5.7, p = 0.0012. %FO was not significantly different in the early hPOCUS group, median difference -1.6%, 95% CI -3.2 to 0.03, p = 0.06. After controlling for confounders, %FO was significantly lower in the early hPOCUS group, ß-coefficient= -2.76, 95% CI -4.7 to -0.6, p = 0.012. Those with early hPOCUS had lower occurrence of severe FO 11.3% vs. 22.9%, p = 0.006; adjusted OR 0.41, 95% CI 0.22 to 0.76, p = 0.005. Conclusions: Early hPOCUS assessment during septic shock resuscitation was independently associated with decreased FO. Prospective research is needed to optimize hPOCUS use in pediatric septic shock management.

Introduction: Air leak is a common complication of necrotizing pneumonia in critically ill children. Severe air leaks impact effective oxygenation and ventilation, oftentimes necessitating multiple thoracostomy tubes and extracorporeal support. Endobronchial valves (EBV) are a minimally invasive intervention to control air leak that may expedite de-escalation of care for critically ill children with necrotizing pneumonia. Methods: A retrospective case series was conducted on patients at the Children's Hospital of Philadelphia who were hospitalized in the pediatric intensive care unit, required extracorporeal membrane oxygenation (ECMO), and underwent placement of one or more EBVs for air leak from July 2023 through August 2024. Results: Six patients, median age 12 years (range 18 months to 18 years), were hospitalized for necrotizing pneumonia complicated by severe air leak and required ECMO. The most common etiology was a viral infection with bacterial co-infection. The median number of EBVs placed per patient was five. The median total time on ECMO was 10 days, with a median duration of 3.5 days after valve placement. The median duration of antibiotic therapy was 47 days (range 24 to 126 days). One patient had a contralateral pneumothorax after valve placement, and another died due to progression of multiorgan failure that began before EBV placement. The five surviving patients were discharged from the hospital, weaned from all respiratory support, and their valves were removed without complication. Conclusion: Endobronchial valves are a feasible intervention for severe air leak in critically ill children with necrotizing pneumonia and may expedite liberation from ECMO.

IMPORTANCE: Right atrial (RA) dysfunction is associated with worse outcomes in some populations with pulmonary hypertension or respiratory failure but the prevalence and correlates of RA dysfunction in pediatric acute respiratory distress syndrome (PARDS) are unknown. OBJECTIVES: The aim of this study was to evaluate RA function by characterizing the prevalence and pattern of RA dysfunction within the first 24 hours of PARDS onset. We hypothesized that RA dysfunction would be common and correlate with the presence of pulmonary hypertension and right ventricular (RV) systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, single-center cohort study at a tertiary care PICU of children (< 18 yr) with a clinically obtained echocardiogram within 24 hours following PARDS diagnosis and healthy controls without cardiopulmonary disease. MAIN OUTCOMES AND MEASURES: Echocardiograms were evaluated for conventional and speckle-tracking (or strain) echocardiographic measures of RA and RV systolic function. Nonparametric summary statistics, comparisons, and correlational analyses were completed. RESULTS: Ninety-two PARDS patients and 55 controls were included. Using a priori thresholds (> 2 sds of control values), 49% (n = 45) of PARDS patients demonstrated RA dysfunction in at least one RA functional metric. The maximal RA strain during the reservoir phase was reduced in PARDS compared with controls (median 40.2% vs. 53.7%; p < 0.001). Patients with echocardiographic evidence of pulmonary hypertension had lower maximal RA strain during the reservoir phase (31.7%) compared with patients without (40.5%; p < 0.05). Patients with higher brain-type natriuretic peptide plasma concentrations had worse RA function. RA function significantly correlated with conventional and strain measures of RV systolic function. CONCLUSIONS AND RELEVANCE: RA dysfunction is common within the first 24 hours of PARDS onset. RA dysfunction during the reservoir phase is associated with pulmonary hypertension and RV systolic dysfunction. Future studies investigating trajectories of RA function and their association with outcomes in PARDS patients are needed.

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.

OBJECTIVE: To determine the association of venovenous extracorporeal membrane oxygenation (VV-ECMO) initiation with changes in vasoactive-inotropic scores (VISs) in children with pediatric acute respiratory distress syndrome (PARDS) and cardiovascular instability. DESIGN: Retrospective cohort study. SETTING: Single academic pediatric ECMO center. PATIENTS: Children (1 mo to 18 yr) treated with VV-ECMO (2009–2019) for PARDS with need for vasopressor or inotropic support at ECMO initiation. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas values, VIS, mean airway pressure (mPaw), and oxygen saturation (Spo ₂) values were recorded hourly relative to the start of ECMO flow for 24 hours pre-VV-ECMO and post-VV-ECMO cannulation. A sharp kink discontinuity regression analysis clustered by patient tested the difference in VISs and regression line slopes immediately surrounding cannulation. Thirty-two patients met inclusion criteria: median age 6.6 years (interquartile range [IQR] 1.5–11.7), 22% immunocompromised, and 75% had pneumonia or sepsis as the cause of PARDS. Pre-ECMO characteristics included: median oxygenation index 45 (IQR 35–58), mPaw 32 cm H₂ o (IQR 30–34), 97% on inhaled nitric oxide, and 81% on an advanced mode of ventilation. Median VIS immediately before VV-ECMO cannulation was 13 (IQR 8–25) with an overall increasing VIS trajectory over the hours before cannulation. VISs decreased and the slope of the regression line reversed immediately surrounding the time of cannulation (robust p < 0.0001). There were pre-ECMO to post-ECMO cannulation decreases in mPaw (32 vs 20 cm H₂ o, p < 0.001) and arterial Pco ₂ (64.1 vs 50.1 mm Hg, p = 0.007) and increases in arterial pH (7.26 vs 7.38, p = 0.001), arterial base excess (2.5 vs 5.2, p = 0.013), and SpO₂ (91% vs 95%, p = 0.013). CONCLUSIONS: Initiation of VV-ECMO was associated with an immediate and sustained reduction in VIS in PARDS patients with cardiovascular instability. This VIS reduction was associated with decreased mPaw and reduced respiratory and/or metabolic acidosis as well as improved oxygenation.