Randomized European Multicenter Trial of Surfactant Replacement Therapy for Severe Neonatal Respiratory Distress Syndrome: Single Versus Multiple Doses of Curosurf
There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial effects of a single large dose of Curosurf (200 mg/kg) in babies with severe respiratory distress syndrome (arterial to alveolar oxygen tension ratio ∼0.10) could be enhanced by using multiple doses of surfactant. Preterm neonates (birth weight 700 to 2000 g) with severe respiratory distress syndrome requiring artificial ventilation with fraction of inspired oxygen ≥0.6 were randomized into two groups at an age of 2 to 15 hours. Both groups received the usual dose of Curosurf(200 mg/kg) immediately after randomization. In neonates randomized to receive multiple-dose treatment, two additional doses of Curosurf (100 mg/kg each) were instilled into the airways (12 and 24 hours after the initial dose) provided that the patients still needed artificial ventilation with fraction of inspired oxygen >0.21. In both groups (single dose: n = 176, multiple doses: n = 167) there was a rapid improvement in oxygenation as reflected by a threefold increase in arterial to alveolar oxygen tension ratio within 5 minutes after surfactant instillation (P < .001), and peak inspiratory pressure and mean airway pressure could be reduced significantly during the first 6 hours after surfactant treatment. In addition, ventilatory requirement (peak inspiratory pressure, ventilatory efficiency index) was reduced in the multiple-dose group 2 to 4 days after randomization (P < .05 to .01). Sixty-five percent of the patients randomized to the multiple-dose regimen and 68% of the single-dose group needed supplemental oxygen 12 hours after the first treatment. Analysis of 28-day outcome data showed a reduction of the incidence of pneumothorax in the multiple-dose group (9% vs 18%, P < .01). The primary end point, of combined incidence of mortality and bronchopulmonary dysplasia, was 33% in the single-dose group and 27% in the multiple-dose group (P = .08). Mortality at 28 days was reduced from 21% in the single-dose group to 13% in the multiple-dose group (P < .05 by logistic regression). It is concluded that treatment with multiple doses of surfactant is more effective than single-dose treatment in severe neonatal respiratory distress syndrome, further reducing pneumothorax mortality.
- Received March 12, 1991.
- Accepted June 13, 1991.
- Copyright © 1992 by the American Academy of Pediatrics