ArticlesUK collaborative randomised trial of neonatal extracorporeal membrane oxygenation
Introduction
Extracorporeal membrane oxygenation (ECMO) is a complex technique for providing life support in respiratory failure. This technique oxygenates blood outside the body, obviating the need for gas exchange in the lungs, and, if necessary, provides cardiovascular support. ECMO is most commonly used to support mature newborn infants. This application is controversial, principally because of varying interpretation of the available evidence.1 Most claims about the value of ECMO in comparison with less invasive forms of life support have been based on case series from the Extracorporeal Life Support Organisation2 and on studies with historical controls. Such studies have suggested large reductions in mortality but they were conducted at a time when neonatal death rates were falling.3, 4 The three small randomised controlled trials of neonatal ECMO that have been reported suggested reductions in mortality but were not conclusive.5, 6, 7, 8 The first two5, 6 used adaptive designs, which may have introduced bias if the threshold for ECMO became more lenient over time, leading to the inclusion of very few infants managed with conventional ventilation. Their results are therefore hard to interpret. The third trial used a standard randomised controlled design, but the number of infants recruited was small and the study has been reported only as conference abstracts.7, 8
Neonatal ECMO was introduced into the UK in 1989. Some clinicians were reluctant to refer potentially suitable infants for ECMO because of concerns that improved survival with the technique might be offset by an increased risk of long-term disability. Others were concerned about the costs of ECMO while uncertainty about its clinical effectiveness and cost-effectiveness persisted.
Against this background, British clinicians agreed to limit neonatal ECMO to use within a randomised controlled trial. This national study compared a policy of transfer for consideration of ECMO with continued conventional management without transfer. Because of concern about quality of survival, the principal outcome measure was death or severe disability at 1 year of age. Our hypothesis was that a policy of referral for ECMO would reduce the proportion of infants who died or survived with severe disability in comparison with conventional management. This report concentrates on the findings to hospital discharge, with preliminary information from the 1-year follow-up.
Section snippets
Trial organisation
The trial was overseen by a multidisciplinary steering group supported by advisory groups on technical aspects of ECMO, developmental follow-up, health economics, pathology, respiratory follow-up, and liaison with parents and relevant voluntary organisations. The clinical coordinating centre was in Leicester and the data-coordinating centre in Oxford. An independent data-monitoring committee was established to review accumulating data; its terms of reference stated that interim results should
Results
185 infants were enrolled in the trial (93 allocated ECMO and 92 allocated conventional management). A further 48 infants were registered but not formally enrolled because of death (14), improvement (19, of whom four later died) and parental refusal (15, of whom nine later died). This report describes outcome up to hospital discharge for all 185 infants, with further information about the status at 1 year for the 124 infants who were enrolled before December, 1994.
At trial entry (table 1) about
Discussion
The trial results leave little doubt that allocation to the ECMO policy reduced the risk of death or severe disability. Potential bias was kept to a minimum by strict random allocation, complete follow-up, and assessment of outcome without knowledge of treatment allocation. Estimates of improved survival were sufficiently large and sufficiently precise to rule out an absence of effect, even in the subgroup analyses. No other study of ECMO has these strengths. There are, nevertheless, other
References (23)
- et al.
Extracorporeal membrane oxygenation and neonatal respiratory failure: experience from the Extracorporeal Life Support Organization
J Pediatr Surg
(1991) - et al.
Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomised prospective trial
J Pediatr
(1985) - et al.
Hidden mortality associated with extracorporeal membrane oxygenation
J Pediatr
(1990) - et al.
ECMO and outcome of mechanical ventilation in infants of birthweight over 2 kg
Lancet
(1990) Statist Sci
(1989)Persistent fetal circulation and extracorporeal membrane oxygenation
Lancet
(1988)- et al.
Survival of infants with persistent pulmonary hypertension without extracorporeal membrane oxygenation
Pediatrics
(1989) - et al.
Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomised study
Pediatrics
(1989) Extracorporeal life support for cardiopulmonary failure
Curr Probl Surg
(1990)- et al.
Prospective randomized controlled trial of conventional treatment or transport for ECMO in infants with persistent pulmonary hypertension (PPHN)
Pediatr Res
(1992)
Prospective randomized controlled trial of conventional treatment or transport for ECMO in infants with severe persistent pulmonary hypertension (PPHN): two year follow up
Pediatr Res
Cited by (0)
Study organisation and participants listed at end of article