Elsevier

The Lancet

Volume 348, Issue 9020, 13 July 1996, Pages 75-82
The Lancet

Articles
UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation

https://doi.org/10.1016/S0140-6736(96)04100-1Get rights and content

Summary

Background

Extracorporeal membrane oxygenation (ECMO) is a complex and expensive technology that can be used to provide temporary support during respiratory failure. Its value for mature newborn infants is controversial because of varying interpretation of the available evidence. We undertook a collaborative trial throughout the UK to assess whether a policy of referral for ECMO has a beneficial effect on survival to 1 year without severe disability in comparison with conventional management.

Methods

Between 1993 and 1995, 185 mature (gestational age at birth ⩾35 weeks, birthweight ⩾2 kg) newborn infants with severe respiratory failure (oxygenation index ⩾40) were enrolled from 55 hospitals in a randomised comparison of either referral to one of five specialist centres for consideration of ECMO or continued intensive conventional management at the original hospital. The most common diagnoses were persistent pulmonary hypertension due to meconium aspiration, congenital diaphragmatic hernia, isolated persistent fetal circulation, sepsis, and idiopathic respiratory distress syndrome. Of the infants allocated ECMO, 84% received this support. Recruitment to the trial was stopped early (November, 1995) by the trial steering committee on the advice of the independent data-monitoring committee, because the data accumulated showed a clear advantage with ECMO. 124 children were enrolled before December, 1994; those who survived to 1 year of age have undergone neurological assessment at that age (by one of three developmental paediatricians unaware of treatment allocation).

Findings

Overall, 81 (44%) infants died before leaving hospital, and two are known to have died later. Death rates differed between the two trial groups; 30 of 93 infants allocated ECMO died compared with 54 of 92 allocated conventional care. The relative risk was 0·55 (95% CI 0·39–0·77; p=0·0005), which is equivalent to one extra survivor for every three to four infants allocated ECMO. The difference in survival applied irrespective of the primary diagnosis, disease severity, and type of referral centre. The benefit of ECMO was also found for the primary outcome measure of death or disability at 1 year (among 124 children enrolled before December, 1994). One child in each group has severe disability (overall Griffiths' developmental quotient <50, or untestable), and 16 (ten ECMO, six conventional management) have impairments with a lesser degree of disability.

Interpretation

These preliminary results demonstrate the clinical effectiveness of a well-staffed and organised neonatal ECMO service. ECMO support should be actively considered for neonates with severe but potentially reversible respiratory failure.

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

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  • Cited by (0)

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