Effects of early indomethacin administration on oxygenation and surfactant requirement in low birth weight infants

Abstract

A previous study found that early intravenous indomethacin administration prolonged respiratory support in very low birth weight infants. We have, therefore, designed a randomized, double blind controlled study to evaluate the oxygenation, and surfactant requirements in preterm low birth weight infants receiving early indomethacin administration. Premature neonates who received surfactant therapy and on mechanical ventilation were prospectively randomized to receive either placebo or indomethacin (0.2 mg/kg intravenously at 12 postnatal hours and every 24 h for two more doses). Oxygenation was assessed by FiO2 required and arterial/alveolar oxygen (a/A O2) ratio during the first 48 h of life. The doses of surfactant were compared between the two groups. Twenty-seven infants (n = 14 of early indomethacin and n = 13 of placebo group) fulfilled inclusion criteria. At admission to the study, there were no differences in the birth weight, gestational age, sex, Apgar scores, a/A O2 ratio, and FiO2. The control group exhibited a significant improvement in oxygenation (FiO2 requirement and a/A O2 compared with the early indomethacin group at 24 (P = 0.026 and 0.02, respectively) and 48 h of life (P = 0.037 and 0.026, respectively). The requirement of surfactant was significantly larger in the early indomethacin group (P = 0.029). Early indomethacin administration increases oxygen and surfactant requirement.

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

“…In a randomized-controlled trial of early prophylactic indomethacin, indomethacin-treated infants required significantly more oxygen, had larger alveolar-arterial oxygen gradients, and needed more doses of surfactant. 104 In the Trial of Indomethacin Prophylaxis in Preterms, 123 infants given prophylactic indomethacin required more oxygen on days 3 through day 7 (Figure 7a). In a third trial, earlier use of indomethacin (day 3 vs day 7) in infants <28 weeks gestation was associated with higher oxygen (Figure 7b) and mean airway pressure (Figure 7c) requirements.…”

Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis

“…The exact method of randomisation was specified in 12 of the studies. [3][4][5][6][7][8][9][10][11][12][13][14] Methods included telephone randomisation, sealed envelopes, and coded drug vials. In the remaining seven trials it was not possible to determine how well the process of randomisation was blinded.…”

Patent ductus arteriosus: to treat or not to treat?

“…Surgical ligation is also associated with diaphragmatic paresis,8 life-long paresis of the left vocal cord9 and late development of scoliosis 10. Randomised trials of early indomethacin demonstrated prolongation of ventilator support,11 worse oxygenation and increased surfactant requirements,12 and requirements for higher mean airway pressures13 and inspired oxygen concentrations 13 14. Treatment with indomethacin has been associated with spontaneous intestinal perforation,15 impaired renal function16 and altered cerebrovascular autoregulation 17.…”