A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Prevention of gram-positive sepsis in neonates weighing less than 1500 grams.

A prospective, randomized study to evaluate the effectiveness of a continuous low-dose vancomycin infusion to prevent nosocomial gram-positive bacteremia was initiated within the first 2 weeks of life in neonates weighing < 1500 gm. Seventy-one infants received constant infusion of vancomycin (25 micrograms/ml) mixed with their total parenteral nutrition solution; 70 infants served as control subjects. The groups were clinically similar in birth weight, estimated gestational age, and severity of illness. Administration of vancomycin was begun at a mean age of 5.4 +/- 2.9 days. Infants had mean serum vancomycin concentrations of 2.4 micrograms/ml, and received vancomycin for a mean of 11 +/- 7 days. No vancomycin-resistant organisms were detected in surveillance cultures during the 2-year study period. Twenty-four of seventy control infants, in comparison with 1 of 71 infants receiving vancomycin, had gram-positive bacteremia (p < 0.001). The addition of a low dose of vancomycin to alimentation fluids virtually eliminated the incidence of gram-positive bacteremia in an at-risk population of very low birth weight infants. However, the widespread use of vancomycin in total parenteral nutrition solution is not recommended until better data on the emergence of vancomycin-resistant organisms are available.

Effect of heparin infusates in umbilical arterial catheters on frequency of thrombotic complications.

We studied 111 infants requiring an umbilical artery catheter, 59 with heparin and 52 without. Thirty-four thrombi were detected, 16 in the heparin group and 18 in the control group. The numbers of thrombi in the two groups was not significantly different, but the number of clotted or nonfunctioning umbilical artery catheters was greater in the control group (P less than 0.05), as was the incidence of hypertension (P less than 0.05). There were no other significant differences between the two groups. We conclude that the use of low doses of heparin may not change the incidence of umbilical artery catheter-related thrombi, but it does appear to lower the incidence of their sequelae.