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.