COMPARISON OF THE EFFECT OF 3 DOSES OF A SYNTHETIC SURFACTANT ON THE ALVEOLAR-ARTERIAL OXYGEN GRADIENT IN INFANTS WEIGHING GREATER-THAN-OR-EQUAL-TO-1250 GRAMS WITH RESPIRATORY-DISTRESS SYNDROME

The effect of a 50% increment or decrement in the recommended 5 ml/kg dose of a commercially available surfactant (Exosurf Neonatal) on the alveolar-arterial oxygen gradient was investigated in a multicenter, d ouble-blind, placebo-controlled rescue trial conducted at 15 hospitals in the United States. Two doses of three different volumes (2.5, 5.0, and 7.5 ml/kg) were compared with two 5.0 ml/kg doses of air in 281 i nfants weighing greater than or equal to 1250 gm who had respiratory d istress syndrome requiring mechanical ventilation and an arterial/alve olar oxygen ratio < 0.22. The first dose was given between 2 and 26 ho urs of age, and the second dose was given 12 hours later to all infant s who still required mechanical ventilation. Infants were stratified a t entry by gender and the magnitude of the arterial/alveolar oxygen ra tio. The air placebo arm of the study was terminated early when reduct ions in mortality rates were proved in another rescue trial of this su rfactant in infants with the same birth weights. For the first 48 hour s, administration of a 2.5 ml/kg dose of surfactant provided less impr ovement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5 ml/kg, which were equivalent. Similar results were observed in me an airway pressure (p < 0.05). There were no significant differences a mong the three dosage groups in mortality rate, air leak, bronchopulmo nary dysplasia, and other complications of prematurity. There were no pulmonary hemorrhages in any group. Reflux of surfactant occurred more frequently in the 5.0 and 7.5 ml/kg groups. These results indicate th at more sustained improvements in oxygenation are provided, with equal safety, by the standard two 5.0 ml/kg rescue doses of this surfactant than by the 2.5 ml/kg dose. No further benefit is gained from two lar ger doses given 12 hours apart.