Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome

Objective: To compare efficacy and side effects of early versus late indome thacin treatment for patent ductus arteriosus (PDA) in premature infants. Methods: One hundred twenty-seven neonates receiving ventilatory assistance (gestational age: 26-31 weeks) with PDA confirmed by echocardiography were randomly assigned in a prospective multicenter trial to either early (day 3, n = 64) or late (day 7 n = 63) intravenous indomethacin treatment (3 x 0 .2 mg/kg every 12 hours). Treatment history and side effects were registere d. Results: The PDA closure rate was higher in the early treatment group at bo th 6 (73% vs 44%, P =.0008) and 9 days of age (91% vs 78%, P =.047). Howeve r there was no significant difference in PDA ligation. Urine output was sig nificantly lower (P <.0001), serum creatinine level was higher (P =.016), a nd more indomethacin courses were administered in the early treatment group (70 vs 26). Respiratory support, number of deaths, and intraventricular he morrhages were similar in both groups. However, on the whole, major adverse events (death, necrotizing enterocolitis, and/or localized perforation, ex tension of hemorrhage, or cystic leukomalacia) occurred more frequently in the early treatment group (P =.017). Conclusion: Early indomethacin treatment improves PDA closure but is associ ated with increased renal side effects and more severe complications and ha s no respiratory advantage over late indomethacin administration in ventila ted, surfactant-treated, preterm infants <32 weeks' gestational age.