Effects of two rescue doses of synthetic surfactant in 344 infants with respiratory distress syndrome weighing 750 to 1249 grams: a double-blind, placebo-controlled multicenter Canadian trial. Canadian Exosurf Neonatal Study Group

Abstract

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 13 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 344 infants with birth weights of 750 to 1249 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio less than 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to the infants remaining on mechanical ventilation. Infants were stratified at study entry by birth weight and gender. The trial was terminated short of the targeted sample size because significant reductions in mortality were observed in another rescue trial completed in the United States in the same weight class of infants. Despite premature termination of the trial, the rate of survival without bronchopulmonary dysplasia was increased (61% vs 52%; p = 0.046) in infants treated with surfactant. In addition, there was a significant reduction in the incidence of overall pulmonary air leak (46% vs 32%; p = 0.009), pneumothorax (27% vs 17%; p = 0.023), and pulmonary interstitial emphysema (40% vs 28%; p = 0.018) in infants treated with synthetic surfactant. There was no difference in the incidence of bronchopulmonary dysplasia, apnea, or pulmonary hemorrhage. Significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7 were present. These findings indicate that rescue therapy with synthetic surfactant can improve outcome for premature infants weighing 750 to 1249 gm with respiratory distress syndrome.