PROPHYLACTIC INDOMETHACIN THERAPY IN THE FIRST 24 HOURS OF LIFE FOR THE PREVENTION OF PATENT DUCTUS-ARTERIOSUS IN PRETERM INFANTS TREATED PROPHYLACTICALLY WITH SURFACTANT IN THE DELIVERY ROOM

Objective: To determine whether a course of low-dose indomethacin ther apy, when initiated within 24 hours of birth, would decrease ductal sh unting in premature infants who received prophylactic surfactant in th e delivery room. Design: Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less t han 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after t reatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonrespond ers were treated with standard indomethacin or ligation. Results: Fort y-three infants received indomethacin (birth weight, 915 +/- 209 gm; g estational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (p = not significant), Of 90 infants, 77 (86%) had a PDA by ech ocardiogram on the first day of life before study treatment; 84% of th ese PDAs were moderate or large in size in the indomethacin-treated gr oup compared with 93% in the placebo group. Nine of forty indomethacin -treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018), There were no signifi cant differences between both groups in any of the long-term outcome v ariables, including intraventricular hemorrhage, duration of oxygen th erapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma c reatinine concentration, thrombocytopenia, pulmonary hemorrhage, or ne crotizing enterocolitis. Conclusion: The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delive ry room, decreases the incidence of left-to-right shunting at the leve l of the ductus arteriosus.