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.

The Influence of the Extracorporeal Membrane Oxygenation Circuit and Components on Anticoagulation Management: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: Management of ECMO anticoagulation in the setting of different ECMO circuit components. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. 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 or good practice statements for the influence of ECMO circuit and components on anticoagulation management. 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. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented. CONCLUSIONS: The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes.

Transcatheter Axial Pump Use in Pediatric Patients on Veno-Arterial Extracorporeal Membrane Oxygenation: An ACTION Collaborative Experience.

We report the largest pediatric multicenter experience with Impella pump use and peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Utilizing the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) collaborative database, we conducted a retrospective, multicenter study of all patients with cardiogenic shock requiring VA-ECMO support with subsequent Impella implant between October 2014 and December 2021. The primary outcome was defined as death while on Impella support. Secondary outcomes were recovery, transplantation, and transition to durable ventricular assist device (VAD) at the time of Impella explantation. Adverse events were defined according to the ACTION registry criteria. Twenty subjects were supported with Impella; Impella 2.5 (n = 3), CP (n = 12), 5.0/5.5 (n = 5). The median Interquartile range (IQR) age, weight, and body surface area at implantation were 15.6 years (IQR = 13.9-17.2), 65.7 kg (IQR = 53.1-80.7), and 1.74 m2 (IQR = 1.58-1.98). Primary cardiac diagnoses were dilated cardiomyopathy/myocarditis in nine (45%), congenital heart disease in four (20%), graft failure/rejection in four (20%), and three (15%) others. Most common adverse events included hemolysis (50%) and bleeding (20%). There were two deaths (10%) in the cohort. Nine patients (45%) were explanted for recovery, eight (40%) were transitioned to a durable VAD, and one (5%) underwent heart transplantation. Impella percutaneous pump support should be considered in the older pediatric population supported with peripheral VA-ECMO, as a means of left heart decompression, and a strategy to come off ECMO to achieve endpoints of myocardial recovery, transition to a durable VAD, or transplantation.

Successful Use of Intravenous Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Pediatric Patients.

Objectives Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC). Case series have described the use of methylnaltrexone for OIC in the pediatric oncology population. There are limited data describing its intravenous use in critically ill pediatric patients. Methods We conducted a retrospective observational study at St. Louis Children's Hospital. Patients less than 18 years old who received at least one dose of intravenous methylnaltrexone while admitted to an intensive care unit between January 2016 and August 2019 were included. The primary outcome was documented laxation within 24 hours of methylnaltrexone administration. Results Sixteen patients received a total of 34 doses of intravenous methylnaltrexone. Patients received a median of 1.69 (interquartile range [IQR], 0.9-4.86) morphine milligram equivalents per kilogram per 24 hours, over a median of 14 days (IQR, 11-30), before methylnaltrexone administration. The median dose of methylnaltrexone was 0.15 mg/kg (IQR, 0.15-0.16). Ten patients (63%) responded to the first dose of methylnaltrexone, and 14 patients (88%) responded to at least one dose. Overall, 26 doses (76%) led to patient response. Four patients (25%) experienced adverse events (emesis, abdominal pain) after methylnaltrexone administration. No signs or symptoms of opioid withdrawal were documented. Conclusions Intravenous methylnaltrexone appears to be safe and effective in treating OIC in critically ill pediatric patients. No serious adverse events or signs of opioid withdrawal were observed after single and repeat dosing. Patients responded to methylnaltrexone with varying opioid dosing and durations prior to administration.

An International Survey of Extracorporeal Membrane Oxygenation Education and Credentialing Practices.

Background: The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly over the past decades because of evolving indications, advances in circuit technology, and encouraging results from modern trials. Because ECMO is a complex and highly invasive therapy that requires a multidisciplinary team, optimal education, training, and credentialing remain a challenge. Objective: The primary objectives of this study were to investigate the prevalence and application of ECMO education and ECMO practitioner credentialing at ECMO centers globally. In addition, we explored differences among education and credentialing practices in relation to various ECMO center characteristics. Methods: We conducted an observational study of ECMO centers worldwide using a survey querying participants in two major domains: ECMO education and ECMO practitioner credentialing. Of note, the questionnaire included ECMO program characteristics, such as type and size of hospital and ECMO experience and volume, to explore the association with the two domains. Results: A total of 241 (32%) of the 732 identified ECMO centers responded to the survey, representing 41 countries across the globe. ECMO education was offered at 221 (92%) of the 241 centers. ECMO education was offered at 105 (98.0%) high-ECMO volume centers compared with 136 (87.5%) low-ECMO volume centers (P = 0.005). Credentialing was established at 101 (42%) of the 241 centers. Credentialing processes existed at 52 (49.5%) high-ECMO volume centers compared with 51 (37.5%) low-ECMO volume centers (P = 0.08) and 101 (49.3%) Extracorporeal Life Support Organization centers compared with 1 (2.7%) non-Extracorporeal Life Support Organization center (P < 0.001). Conclusion: We found significant variability in whether ECMO educational curricula are offered at ECMO centers. We also found fewer than half of the ECMO centers surveyed had established credentialing programs for ECMO practitioners. Future studies that assess variability in outcomes among centers with and without standardized educational and credentialing practices are needed.

In vivo measurement of pediatric extracorporeal oxygenator insensible losses; a single center pilot study.

Introduction: Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous in vitro studies have attempted to quantify oxygenator-related insensible losses, as failure to account for this fluid loss may lead to inaccurate fluid balance assessment and potentially harmful clinical management, such as unnecessary exposure to diuretics, slow continuous ultrafiltration (SCUF), or continuous kidney replacement therapy (CKRT). We performed a novel in vivo study to measure insensible fluid losses in pediatric ECMO patients. Methods: Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow. Results and discussion: Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m2 IQR [0.315, 1.3725]. Overall, the cohort had a median sweep of 2.5 L/min [0.9, 4], ECMO flow of 3.975 L/m2/min [0.75, 4.51], and a set ECMO temperature of 37 degrees Celsius [36.6, 37.2]. The calculated net water loss per L/min of sweep was 75.93 ml/day, regardless of oxygenator size or patient weight. There was a significant difference in median documented vs. calculated fluid balance incorporating the insensible fluid loss, irrespective of oxygenator size (pediatric oxygenator: 7.001 ml/kg/day [-12.37, 28.59] vs. -6.11 ml/kg/day [-17.44, 13.01], respectively, p = 0.005 and adult oxygenator: 14.36 ml/kg/day [1.54, 25.77] and 9.204 ml/kg/day [-1.28, 22.05], respectively, p = <0.001). We present this pilot study of measured oxygenator-associated insensible fluid losses on ECMO. Our results are consistent with prior in vitro methods and provide the basis for future studies evaluating the impact of incorporating these fluid losses into patients' daily fluid balance on patient management and outcomes.

Single Ventricular Assist Device Care and Outcomes for Failed Stage I Palliation: A Single-Center Decade of Experience.

Single ventricular assist device (SVAD) use before and after stage I palliation (S1P) is increasing with limited data on outcomes. To address this knowledge gap, we conducted a single-center retrospective review to assess pre- and post-SVAD clinical status, complications, and outcomes. We leveraged a granular, longitudinal, local database that captures end-organ support, procedural interventions, hematologic events, laboratory data, and antithrombotic strategy. We identified 25 patients between 2013 and 2023 implanted at median age of 53 days (interquartile range [IQR] = 16-130); 80% had systemic right ventricles and underwent S1P. Median SVAD days were 54 (IQR = 29-86), and 40% were implanted directly from ECMO. Compared to preimplant, there was a significant reduction in inotrope use ( p = 0.013) and improved weight gain ( p = 0.008) post-SVAD. Complications were frequent including bleeding (80%), stroke (40%), acute kidney injury (AKI) (40%), infection (36%), and unanticipated catheterization (56%). Patients with in-hospital mortality had significantly more bleeding complications ( p = 0.02) and were more likely to have had Blalock-Thomas-Taussig shunts pre-SVAD ( p = 0.028). Survival to 1 year postexplant was 40% and included three recovered and explanted patients. At 1 year posttransplant, all survivors have technology dependence or neurologic injury. This study highlights the clinical outcomes and ongoing support required for successful SVAD use in failed single-ventricle physiology before or after S1P.

Long-Term Neurobehavioral and Functional Outcomes of Pediatric Extracorporeal Membrane Oxygenation Survivors.

There are limited reports of neurobehavioral outcomes of children supported on extracorporeal membrane oxygenation (ECMO). This observational study aims to characterize the long-term (≥1 year) neurobehavioral outcomes, identify risk factors associated with neurobehavioral impairment, and evaluate the trajectory of functional status in pediatric ECMO survivors. Pediatric ECMO survivors ≥1-year postdecannulation and ≥3 years of age at follow-up were prospectively enrolled and completed assessments of adaptive behavior (Vineland Adaptive Behavior Scales, Third Edition [Vineland-3]) and functional status (Functional Status Scale [FSS]). Patient characteristics were retrospectively collected. Forty-one ECMO survivors cannulated at 0.0-19.8 years (median: 2.4 [IQR: 0.0, 13.1]) were enrolled at 1.3-12.8 years (median: 5.5 [IQR: 3.3, 6.5]) postdecannulation. ECMO survivors scored significantly lower than the normative population in the Vineland-3 Adaptive Behavior Composite (85 [IQR: 70, 99], P < 0.001) and all domains (Communication, Daily Living, Socialization, Motor). Independent risk factors for lower Vineland-3 composite scores included extracorporeal cardiopulmonary resuscitation, electrographic seizures during ECMO, congenital heart disease, and premorbid developmental delay. Of the 21 patients with impaired function at discharge (FSS ≥8), 86% reported an improved FSS at follow-up. Pediatric ECMO survivors have, on average, mild neurobehavioral impairment related to adaptive functioning years after decannulation. Continued functional recovery after hospital discharge is likely.