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ABSTRACT
Intro: Extracorporeal membrane oxygenation for neonatal and pediatric respiratory failure continues to demonstrate improving outcomes, largely due to advances in technology along with refined management strategies despite mounting patient acuity and complexity. Successful use of ECMO requires thoughtful initiation and candidacy strategies, along with reducing the risk of ventilator induced lung injury and the progression to multiorgan failure.
Areas Covered: This review describes current ECMO management strategies for neonatal and pediatric patients with acute refractory respiratory failure and summarizes relevant published literature. ECMO initiation and candidacy, along with ventilator and sedation management, are highlighted. Additionally, rapidly expanding areas of interest such as anticoagulation strategies, transfusion thresholds, rehabilitation on ECMO, and drug pharmacokinetics are described.
Expert Opinion: Over the last few decades, published studies supporting ECMO use for acute refractory respiratory failure, along with institutional experience, have resulted in increased utilization although more randomized-controlled trials are needed. Future research should focus on filling the knowledge gaps that remain regarding anticoagulation, transfusion thresholds, ventilator strategies, sedation, and approaches to rehabilitation to subsequently implement into clinical practice. Additionally, efforts should focus on well-designed trials, including population pharmacokinetic studies, to develop dosing recommendations.
Article highlights
As no validated tool exists for extracorporeal membrane oxygenation inclusion/exclusion criteria for neonatal and pediatric patients with acute respiratory failure, of the utmost importance is the presence of a reversible disease process where ECMO serves to support organ rest and allow recovery. Further specific criteria for ECMO are institution-specific and highly variable; most candidacy decisions are made through multidisciplinary discussions.
Early initiation of ECMO before the development of multiorgan failure and ventilator induced lung injury may improve outcomes. However, the survivable duration of ventilation prior to ECMO has been extended in the era of lung protective ventilation.
Ventilator management on ECMO should prioritize lung protective ventilation to avoid ventilator-induced lung injury. Data on ancillary management strategies including bronchoscopy and surfactant administration are lacking but are likely to be safe.
Bleeding and clotting remain among the most common complications on ECMO. Recent data suggest most centers still use heparin, although a small number have moved to exclusive use of bivalirudin. Antithrombin continues to be of interest in those who use heparin and studies to date yield conflicting results regarding supplementation and outcomes such as bleeding and thrombotic complications.
As studies have shown increased mortality associated with volume of transfusion on ECMO, along with the development of guidelines, the overall trend of transfusions on ECMO has grown more conservative yet remains highly variable among centers.
Sedation should be minimal, as the patient’s safety allows, and efforts focused on rehabilitation – particularly in the bridge to lung transplant.
Drug pharmacokinetics in ECMO have been shown to be varied, either by direct extraction via the circuit, changed volume of distribution, or altered clearance. Antimicrobials, anticonvulsants, and sedative and analgesic agents have been studied mostly in the neonatal population; pediatric studies are lacking.
High membrane pressures, air in the circuit, circuit clotting, tamponade physiology from multiple etiologies and cannula dislodgement are among the ECMO emergencies team members must know how to troubleshoot.
Areas of future research include anticoagulation and transfusion management, pharmacokinetics, ventilator strategies, ancillary therapies and sedation management while on ECMO.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Annotated Bibliography: * of interest, ** of considerable interest
1: ECLS Registry Report 2020
**Most recent registry report from ELSO highlighting outcome trends, center volume, annual neonatal and pediatric runs as well as complications.
8: Maratta 2020
**Most recent pediatric respiratory failure ELSO guidelines.
9: Wild 2020
**Most recent neonatal respiratory failure ELSO guidelines.
15: Zabrocki 2011
*Retrospective analysis of the ELSO database, highlighting predictors of mortality and the increasing complexity of patients supported with ECMO.
21: ELSO Guidelines
**Current general ELSO guidelines.
23: Friedman 2020
**Multicenter retrospective study evaluating whether mechanical ventilation practices were associated with clinical outcomes with results demonstrating the only ventilator setting associated with mortality was FiO2.
24: Pediatric acute respiratory distress syndrome 2015
**Consensus recommendations for pediatric acute respiratory distress syndrome from the Pediatric Acute Lung Injury Consensus Conference.
38: ELSO Anticoagulation Guidelines
**Current ELSO guidelines for anticoagulation.
39: Ozment 2021
**Recent survey of neonatal and pediatric ECMO medical directors in the United States regarding anticoagulation and transfusion practices.
45: Chlebowski 2020
*Recent review of complexities in anticoagulation monitoring and antithrombin supplementation
53: Sanfilippo 2017
*Systematic review of bivalirudin use in adult and pediatric ECMO which
56: Bembea 2018
*From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative – recommendations on indications for red blood cell transfusion in critically ill children receiving extracorporeal support
60: Schneider 2017
*Multicenter analysis comparing sedation strategies in children supported with ECMO with resulting demonstrating substantial sedative exposure after ECMO initiation and increased frequency of iatrogenic withdrawal syndrome.
61: Sutiman 2020
** Systemic review of pharmacokinetics in the most commonly used drugs in critically ill children on ECMO which found significant PK alterations in the majority of drugs studied.
101: Freeman 2014
*Retrospective analysis of center volume and its impact on mortality demonstrating significantly higher mortality in centers with low annual case volume.
102: Gonzalez 2019
*Study evaluating pediatric ECMO center volume and mortality, finding that among high volume centers, there were significantly lower mortality rates.