Elsevier

The Journal of Pediatrics

Volume 138, Issue 2, February 2001, Pages 205-211
The Journal of Pediatrics

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

https://doi.org/10.1067/mpd.2001.110528Get rights and content

Abstract

Objective: To compare efficacy and side effects of early versus late indomethacin 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 × 0.2 mg/kg every 12 hours). Treatment history and side effects were registered. Results: The PDA closure rate was higher in the early treatment group at both 6 (73% vs 44%, P =.0008) and 9 days of age (91% vs 78%, P =.047). However, there was no significant difference in PDA ligation. Urine output was significantly lower (P <.0001), serum creatinine level was higher (P =.016), and more indomethacin courses were administered in the early treatment group (70 vs 26). Respiratory support, number of deaths, and intraventricular hemorrhages were similar in both groups. However, on the whole, major adverse events (death, necrotizing enterocolitis, and/or localized perforation, extension of hemorrhage, or cystic leukomalacia) occurred more frequently in the early treatment group (P =.017). Conclusion: Early indomethacin treatment improves PDA closure but is associated with increased renal side effects and more severe complications and has no respiratory advantage over late indomethacin administration in ventilated, surfactant-treated, preterm infants <32 weeks’ gestational age. (J Pediatr 2001;138:205-11)

Section snippets

Subjects

Neonates admitted to 4 neonatal intensive care units were eligible for enrollment if they met the following inclusion criteria: (1) gestational age <32 weeks, (2) respiratory distress syndrome for which ventilatory support was needed by means of mechanical ventilation (either conventional or prophylactic high-frequency oscillatory ventilation) or continuous positive airway pressure with additional oxygen requirements above 30% fraction of inspired oxygen, (3) age of 3 days, and (4)

Study population

Of the 380 preterm infants with respiratory distress syndrome who were eligible for entry into the study, 127 (33%) had moderate to severe PDA shunting and were randomly assigned to treatment groups (Table I).At the start of the study, echocardiographic evaluations were comparable between early and late treatment groups: ductal diameter (2.5 ± 0.7 mm vs 2.3 ± 0.8 mm; mean ± SD), ductal maximal left-to-right shunt velocity (1.50 ± 0.49 m/s vs 1.52 ± 0.48 m/s), and number of infants with moderate

Discussion

We found that when indomethacin treatment was postponed until the end of the first week of life in infants with PDA confirmed by echocardiography, there was a spontaneous PDA closure in 43% (27/63) of them and a diminution of the ductal left-to-right shunt, alleviating the need for further treatment in another 16% (10/63). Although significantly more infants had a PDA on days 6 and 9 in this late treatment group, the final closure rate and the need for surgical ligation were comparable with

Acknowledgements

We thank the nurses and the staff of the neonatal units for collecting the urine samples and all the clinical data used in this report.

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  • Cited by (0)

    Reprint requests: Bart Van Overmeire, MD, PhD, Department of Pediatrics, Division of Neonatology, University Hospital Antwerpen, Wilrijkstraat 10, B-2650 Edegem, Belgium.

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