2 DOSES OF EARLY INTRAVENOUS DEXAMETHASONE FOR THE PREVENTION OF BRONCHOPULMONARY DYSPLASIA IN BABIES WITH RESPIRATORY-DISTRESS SYNDROME

Bronchopulmonary dysplasia is an important complication of ventilation in babies for which treatment with steroids has been advocated. We re port the results of a phase I study of early i.v. dexamethasone to pre vent the development of bronchopulmonary dysplasia in a high-risk popu lation of ventilated premature babies, < 30 wk gestation, with surfact ant-treated respiratory distress syndrome. This study used a limited d examethasone dosing regimen to minimize toxicity but used administrati on early in the course of acute lung disease to interrupt the injury c ycle. Forty babies were enrolled; 19 were randomized to receive dexame thasone (0.5 mg/kg birth weight at 12-18 h of age and a second dose 12 h later) and 21 were randomized to receive placebo (i.v. saline). The dexamethasone group required less ventilatory support (mean airway, p eak inspiratory and end expiratory pressures, and intermittent mandato ry ventilation) and supplemental oxygen after study d 4 (all p < 0.05, repeated measures analysis of variance). Improved tidal volume in the dexamethasone group, as measured by pulmonary function testing of inf ants who remained intubated, was seen on study d 7 (p = 0.02, t test). The dexamethasone group required shorter hospitalizations (median of 95 d versus 106 d, p = 0.01) (proportional hazards regression). Surviv al in the dexamethasone group was 89% versus 67% in the placebo group (p = 0.08, chi(2) analysis). Survival without bronchopulmonary dysplas ia, diagnosed at 36 wk corrected gestational age, was 68% in the dexam ethasone group versus 43% in the placebo group (p = 0.14). Mean blood pressure was elevated on study d 4 through 7 in the dexamethasone grou p, but this difference resolved by study d 10 without pharmacologic in tervention. No differences in hyperglycemia, incidence of intraventric ular hemorrhage (or its severity), or days to regain birth weight were seen. Early administration of dexamethasone resulted in short-term an d suggested long-term benefits without significant complications. The results of this trial justify a large scale, broader-based (phase II) trial in premature babies with respiratory distress syndrome to determ ine the limits of effectiveness and the incidence of less-frequent pot ential side effects.