Dr. Murphy of the Medical University of South Carolina has no relevant financial relationships to disclose.)
This article includes discussion of extracorporeal membrane oxygenation, extracorporeal life support, and ECMO. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Extracorporeal membrane oxygenation (ECMO), also referred to as extracorporeal life support (ECLS), is an advanced life-support system that provides cardiopulmonary bypass for critically ill patients with select, amenable diseases. In neonatal patients, ECMO is most commonly utilized to support infants with respiratory failure secondary to reversible pulmonary diseases; ECMO has significantly improved the survival and neurodevelopmental outcome in these neonates. In this article, the authors describe the history, patient selection criteria, and medical technology involved in ECMO as well as the neonatal outcomes.
• ECMO is an effective therapy for hypoxic respiratory failure due to reversible pulmonary disease in neonates.
• ECMO is also utilized as adjunctive therapy in the management of neonates with congenital cardiac defects and for neonates requiring emergent cardiopulmonary support.
• ECMO is a cost-effective therapy with excellent neonatal survival rates as well as good long-term outcomes to school age and beyond.
Historical note and terminology
ECMO is a cutting-edge, life-saving technology used most commonly for management of hypoxic respiratory failure in the newborn. ECMO can be provided in one of two ways: (1) venovenous ECMO provides respiratory support in the setting of respiratory failure secondary to reversible, pulmonary, and pulmonary vascular disease processes or (2) venoarterial ECMO 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 ECMO in the neonatal population.
In the past, investigators have attempted to provide extracorporeal circulation to support patients with cardiorespiratory problems. Gibbon, who began work on extracorporeal circulation in 1937, is considered the father of cardiopulmonary bypass. Over the next 20 years, the technique was further refined. In the 1950s it was applied mainly to infants and children requiring surgery for congenital heart disease but with poor results. 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 (Bartlett 1993). Bartlett is credited with pioneering the technique to successfully provide ECMO for neonates with hypoxic respiratory failure. In 1976 he reported the first neonatal patient who survived ECMO, named “Esperanza” (meaning “hope”) by the nurses.
There are now over 300 ECMO centers in the world divided among 60 countries that contribute ECMO data to the International Registry of Extracorporeal Life Support Organization (ELSO). The ELSO registry provides these centers international and center-specific ECMO outcome data for neonatal, pediatric, and adult patients annually.
In 1975, the National Institutes of Health sponsored a randomized control trial of venoarterial ECMO versus conventional treatment in the management of adult respiratory distress syndrome. The trial was stopped in 1979 because less than 10% of patients survived (Zapol et al 1979). Study failure has been attributed to various factors including lack of prior experience with ECMO, a nationwide influenza and pneumonia epidemic during the study period, and significant bleeding complications. Following these discouraging results, more trials in the adult population were discontinued. However, Bartlett, who continued his work on the technique and its application, successfully reported the use of ECMO in the management of neonatal respiratory failure in 1982 (Bartlett et al 1985).
Several notable randomized controlled trials lead the way for ECMO to be common practice today. Bartlett and colleagues conducted a randomized control trial that reported significantly improved survival when enrolled neonatal patients received venoarterial ECMO rather than conventional treatment (Bartlett et al 1985). However, the adaptive randomization technique they utilized, called “play the winner" (ie, if one treatment is more successful, more patients 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 ECMO versus conventional therapy, this time in neonates with persistent pulmonary hypertension (O Rourke et al 1989). Overall survival in the ECMO treated group was higher than in the conventional therapy group (97% ECMO 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 ECMO, it was felt by many to be unethical to randomize patients to the conventional therapy arm. The third randomized control trial of neonatal ECMO included both venoarterial and venovenous ECMO support and was carried out in the United Kingdom from 1993 to 1995. Again, patients treated with ECMO had decreased mortality (32% ECMO vs. 59% conventional; p=0.005; NNT 3-4) compared to those treated with conventional management (UK Collaborative Study Group 1996). A 4-year follow-up showed that death or severe disability was less frequent in ECMO versus the conventional treatment group survivors (37% ECMO vs. 59% Conventional; p=0.004) (Bennett et al 2001). A 7-year follow-up assessed 90 of 100 children and recorded that 66 patients had a cognitive level that was within normal limits. The distribution of learning difficulties was similar between groups. A higher level of behavioral problems was noted in conventionally-treated children, and there was some evidence of reduced morbidity in the ECMO group (McNally et al 2006).
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