Comparison of the effect of three doses of a synthetic surfactant on the alveolar-arterial oxygen gradient in infants weighing > or = 1250 grams with respiratory distress syndrome. American Exosurf Neonatal Study Group II.

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, double-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 infants weighing > or = 1250 gm who had respiratory distress syndrome requiring mechanical ventilation and an arterial/alveolar oxygen ratio < 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to all infants who still required mechanical ventilation. Infants were stratified at entry by gender and the magnitude of the arterial/alveolar oxygen ratio. The air placebo arm of the study was terminated early when reductions in mortality rates were proved in another rescue trial of this surfactant in infants with the same birth weights. For the first 48 hours, administration of a 2.5 ml/kg dose of surfactant provided less improvement in the alveolar-arterial oxygen gradient than doses of 5.0 and 7.5 ml/kg, which were equivalent. Similar results were observed in mean airway pressure (p < 0.05). There were no significant differences among the three dosage groups in mortality rate, air leak, bronchopulmonary 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 that 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 larger doses given 12 hours apart.

The role of host factors in an outbreak of necrotizing enterocolitis.

During an outbreak investigation of necrotizing enterocolitis (NEC) in a neonatal intensive care unit, we identified nine definite and six suspected cases of NEC on the basis of histopathologic, clinical, and roentgenographic findings. Neonates of low birth weight (less than 1,250 g) had the highest incidence of NEC, supporting a role for prematurity in this disease. Patients with definite NEC and those with severe clinical features had significantly lower birth weights and postconception ages (gestational age at birth plus postnatal age at onset of NEC) than the patients with suspected NEC. In a case-control study using birth weight-matched control subjects, maternal toxemia was identified as a possible protective factor for NEC. To our knowledge, this is the first report of the relationship between NEC disease severity and postconception age. These findings also suggest that toxemia may be an important protective factor in NEC and should be examined in subsequent studies.