General Child Neurology
May. 31, 2021
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Extracorporeal life support (ECLS), also referred to as extracorporeal membrane oxygenation (ECMO), is an advanced life-support system that provides cardiopulmonary bypass for critically ill patients with select, amenable diseases. Extracorporeal life support is offered to adult, pediatric, and neonatal patients; however, here we will review neonatal ECLS primarily.
In infants, extracorporeal life support is most commonly utilized to support those with respiratory failure secondary to reversible pulmonary diseases; extracorporeal life support has significantly improved survival and neurodevelopmental outcomes in these neonates. In this article, the authors describe the history, patient selection criteria, and medical technology involved in providing neonatal extracorporeal life support as well as neonatal extracorporeal life support outcomes.
• Extracorporeal life support is an effective therapy for hypoxic respiratory failure due to reversible pulmonary disease in neonates.
• Extracorporeal life support is also utilized as adjunctive therapy in the management of neonates with congenital cardiac defects, neonates with congenital diaphragmatic hernias, and neonates requiring emergent cardiopulmonary support.
• Extracorporeal life support is a lifesaving therapy with excellent neonatal survival rates as well as good long-term outcomes to school age and beyond.
Extracorporeal life support is a cutting-edge, life-saving technology used in all patient populations for those with severe but amenable disease processes. In newborns, ECLS is most commonly utilized for management of hypoxic respiratory failure. Extracorporeal life support can be provided in 1 of 2 ways: (1) venovenous ECLS provides respiratory support in the setting of respiratory failure secondary to reversible, pulmonary, and pulmonary vascular disease processes or (2) venoarterial ECLS provides both cardiac and respiratory support for patients with acute cardiac arrest or cardiorespiratory failure in the setting of congenital heart disease or reversible processes affecting cardiac output. The focus here will be on ECLS in the neonatal population.
Historically, investigators have attempted to provide extracorporeal circulation to support patients with cardiorespiratory problems since the 1930s. Gibbon, who began work on extracorporeal circulation in 1937, is considered the father of cardiopulmonary bypass. However, it was not until the mid-1960s that prolonged extracorporeal circulation was attempted in humans, with the first successful report by Hill and colleagues in 1972 (04). Dr. Robert H. Bartlett, credited with pioneering the technique to successfully provide ECLS for neonates with hypoxic respiratory failure, reported the first successful neonatal ECLS case in a newborn named “Esperanza” (meaning “hope”) in 1975 (03).
Several notable randomized controlled trials lead the way for extracorporeal life support to be common practice today. Bartlett and colleagues conducted a randomized control trial that reported significantly improved survival when enrolled neonatal patients received venoarterial ECLS rather than conventional treatment (03). However, the adaptive randomization technique they utilized, called “play the winner" (ie, if one treatment is more successful, more subjects are randomly assigned to that treatment), was not an established statistical method accepted in the scientific community at the time. In 1989, O’Rourke and associates reported results of a second randomized trial of venoarterial ECLS versus conventional therapy, this time in neonates with persistent pulmonary hypertension (26). Overall survival in the extracorporeal life support treated group was higher than in the conventional therapy group (97% ECLS vs. 60% conventional; p< 0.05). Results of this trial were also not widely accepted due to concerns regarding the study design. In this case, randomization was conducted with a more traditional 50/50 allocation strategy; however, following the deaths of 4 patients in a single study arm, an adaptive favor-the-winner strategy was adopted. Given the promising results seen in patients who received extracorporeal life support, it was felt by many to be unethical to randomize patients to the conventional therapy arm. The third randomized control trial of neonatal extracorporeal life support included both venoarterial and venovenous ECLS support and was carried out in the United Kingdom from 1993 to 1995. Again, patients treated with extracorporeal life support had decreased mortality (32% ECLS vs. 59% conventional; p=0.005; NNT 3-4) compared to those treated with conventional management (30). A 4-year follow-up showed that death or severe disability was less frequent in extracorporeal life support versus the conventional treatment group survivors (37% ECLS vs. 59% Conventional; p=0.004) (07).
Today, the ELSO leads the efforts in collecting extracorporeal life support data. ELSO is an “international, non-profit consortium of health care institutions who are dedicated to the development and evaluation of novel therapies for support of failing organ systems” (ELSO.org). As part of this work, ELSO maintains a registry of extracorporeal life support use in active ELSO centers across the world. There are now over 400 ECLS centers in the world divided among 60 countries. Current regional ECLS chapters include EuroELSO, Asia-Pacific ELSO, Latin American ELSO, and South and West Asian ELSO. Active ELSO centers contribute extracorporeal life support data to the International Registry and the ELSO provides these centers international and center-specific ECLS outcome data for neonatal, pediatric, and adult patients annually. In the most recent ELSO Registry Report (containing registry data through July 2, 2016), information was provided on more than 78,000 extracorporeal life support patients with 58% survival to hospital discharge (29). Historically, neonatal patients have been the largest group represented in the ELSO registry. However, in 2012 to 2013 the annual number of adult extracorporeal life support cases worldwide exceeded pediatric and neonatal cases for the first time following the influenza A (H1N1) pandemic (20).
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