Surfactant replacement therapy in respiratory distress syndrome. Meta-analysis of clinical trials of single-dose surfactant extracts
H. M. Hennes, M. B. Lee, A. A. Rimm and D. L. Shapiro
Department of Pediatrics, Children's Hospital of Wisconsin, Milwaukee 53201.
Replacement therapy with surfactant extracts in premature infants with
respiratory distress syndrome has been evaluated in several clinical
trials. The results of individual trials do not provide conclusive evidence
that administration of a single dose of surfactant improves morbidity or
mortality. Meta-analysis is a statistical method to combine the results of
such clinical trials, and combined analysis provides a means to overcome
the problem of not being able to detect significant small differences in
individual trials due to these small sample sizes. Seven clinical trials
(277 patients treated with nonhuman surfactant extract and 263 controls)
met the criteria for analysis; five outcome measurements (mortality, patent
ductus arteriosus, pneumothorax, intraventricular hemorrhage, and
bronchopulmonary dysplasia) were selected to estimate the treatment effect.
The meta-analysis showed that a single dose of surfactant administered
before the first breath or within 15 hours of birth significantly decreased
the mortality rate (95% confidence interval = -0.19 to -0.03) and the risk
of developing pneumothorax (95% confidence interval = -0.28 to 0.14) in
infants with respiratory distress syndrome. Further clinical trials are
needed to evaluate other aspects of surfactant replacement therapy in
premature infants because inconsistent results were observed among the
seven analyzed studies.
