Surfactant Replacement Therapy for Severe Neonatal Respiratory Distress Syndrome: An International Randomized Clinical Trial

In a randomized multicenter trial, involving the collaboration of eight European neonatal intensive care units, the efficacy of replacement therapy with a new surfactant preparation (Curosurf) was tested in 146 patients with severe neonatal respiratory distress syndrome. Criteria for entry included birth weight 700 to 2,000 g, age when treated two to 15 hours, and requirement of artificial ventilation with Fio2 ≥ 0.6. The babies were treated with a single large dose of surfactant (200 mg/kg) at a median age of nine hours (range two to 15 hours). Average Fio2 before treatment was the same (0.80) for both surfactant-treated patients and control patients. Babies receiving surfactant showed, within five minutes, a dramatic improvement of oxygenation as reflected by a nearly threefold increase of the Pao2/Fio2 ratio. Six hours after randomization, the Pao2/Fio2 ratio still showed a 98% improvement in surfactant-treated patients compared with controls (P < .001), and statistically significant differences in favor of the treated babies persisted until 48 hours after randomization, when surviving control infants began to recover. Treatment with surfactant decreased neonatal (≤28 days) mortality from 51% to 31% (P < .05). Compared with control babies, the surfactant-treated group also had a decreased incidence of pulmonary interstitial emphysema (23% v 39%; P < .05) and pneumothorax (18% v 35%; P < .05). The percentage of survivors without bronchopulmonary dysplasia in the treated group was more than twice that of the control group (55% v 26%; P < .001). Treatment with this surfactant appears to effectively improve lung function and short-term outcome in infants with severe respiratory distress syndrome.