Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

Highlighted lines and questions below provide links to the pertinent description of criteria in The EBM User's Guide, now available at the Canadian Centres for Health Evidence

Article Reviewed:

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UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation.

UK Collaborative ECMO Trial Group.

Lancet 1996; 348: 75-82. [abstract]

and a Commentary by Roger Soll; Lancet 1996; 348: 70-71.)

Reviewed by Adrienne Randolph

Review posted March 17, 1997

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I. What is being studied?:

The study objective:

To assess whether referral for ECMO has a beneficial effect on survival.

The patients included:

Between 1993-95, 185 newborns (gestational age > or = 35 weeks, birthweight > or = 2 kg) with severe respiratory failure (oxygenation index > or = 40) were enrolled from 55 hospitals in the UK. [oxygenation index (OI) calculator from University of Washington ECLS]

The interventions compared:

ECMO support (both venoarterial and venovenous) using a protocol versus conventional management guidelines which included continued ventilation with liberal use of oxygen, correction of acidosis, paralysis, maintenance of adequate blood pressure, and use of any available pulmonary vasodilator (including nitric oxide). Use of high frequency ventilation and surfactant was allowed.

The outcomes evaluated:

Death or severe disability at 1 year of age.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes. Randomization was done using a computerised minimisation algorithm to ensure balance on key prognostic variables - primary diagnosis, disease severity, referral centre, and the ECMO centre in which a cot was reserved.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes. All 185 infants who were randomized were followed up but the neurologic outcomes at 1 year were only available for the 124 infants enrolled before December 1994.

Were patients analyzed in the groups to which they were randomized?

Yes. One patient randomized to conventional ventilation got ECMO owing to a series of randomization errors. Fifteen patients in the ECMO group did not get ECMO because they were too well (3%), too ill (2%), died before transfer (5%), had congenital heart disease (5%) or failed cannulation (1%). However, the analysis was done according to intention-to-treat.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

No. It is impossible to blind the health care workers to ECMO. However, the outcome assessors who performed the developmental evaluation at one year were blind to ECMO status and the area where the ECMO scars would have been was concealed.

4. Were the groups similar at the start of the trial?

Yes. There were similar (<10% difference) numbers of infants in both groups on each individual primary diagnosis, the entry oxygenation index, the age at entry in days, sex, gestational age, birthweight, number of days of high pressure ventilation, use of pulmonary vasodilators, use of high frequency ventilation, and use of surfactant.

5. Aside from the experimental intervention, were the groups treated equally?

No. Between trial entry and hospital discharge fewer infants allocated to ECMO received pulmonary vasodilators (83% versus 96%), surfactant (41% versus 33%), and high frequency ventilation (11% versus 33%). Use of nitric oxide was similar (20% ECMO group versus 22% conventional).

III. What were the results?

1. How large was the treatment effect?

The relative risk of death before discharge was 0.51, with an absolute risk reduction of 29%. This means that for every 3 infants treated with referral for ECMO, one life is saved over treatment with conventional management at the initial center. [Read more about NNT: Number Needed to Treat from NHS Centre for EBM.] The relative risk of known death before age 1 year was 0.55 for ECMO. For the 124 patients who were enrolled before December 1994, the relative risk of death or severe disability at one year was 0.54 for the ECMO referral group versus conventional management.

2. How precise was the estimate of the treatment effect?

The 95% confidence interval for the relative risk of death before discharge was 0.36 to 0.73 for ECMO referral versus conventional therapy. The confidence interval for the absolute risk reduction was 15 to 42. The 95% confidence interval for the relative risk of known death before age 1 year was 0.39 to 0.77 for ECMO referral versus conventional therapy. For the 124 patients who were enrolled before December 1994, the 95% confidence for the relative risk of death or severe disability at one year using ECMO referral was 0.36 to 0.80.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Maybe. The group of patients enrolled was representative of the underlying disorders leading to severe respiratory failure in neonates. About 19% had congenital diaphragmatic hernia, and 37% had persistent pulmonary hypertention due to meconium aspiration. About 17% had isolated persistent fetal circulation, 10% had sepsis, and 11% had IRDS. The management of the patients in the conventional management arm across the 55 centres may differ markedly from your own ventilatory management and no ventilator management protocol is described.

2. Were all clinically important outcomes considered?

Yes. Neurologic disability was evaluated in survivors and mortality was reported up to one year after discharge. The authors also mention that cost and respiratory function is being evaluated and the results will be reported in later studies.

3. Are the likely treatment benefits worth the potential harms and costs?

Yes. Referral for ECMO resulted in a significantly larger number of neurologically functional survivors than conventional management and preliminary cost analysis revealed that the cost (in British pounds) for each survivor would be 24,123 for ECMO and 23,450 for conventional management.

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