Effects of Prophylactic Indomethacin on Vasopressor-Dependent Hypotension in Extremely Preterm Infants

J Pediatr. 2017 Mar:182:21-27.e2. doi: 10.1016/j.jpeds.2016.11.008. Epub 2016 Dec 1.

Abstract

Objective: To determine whether a moderate-to-large patent ductus arteriosus (PDA) is responsible for vasopressor-dependent hypotension, occurring at the end of the first postnatal week.

Study design: We performed a retrospective, double cohort controlled study of infants delivered at ≤27+6 weeks' gestation (n = 313). From January 2004 through April 2011, all infants were treated with prophylactic indomethacin ([PINDO] epoch). From May 2011 through December 2015, no infant was treated with indomethacin until at least 8 postnatal days (conservative epoch). Echocardiograms were performed on postnatal days 6 or 7. Hypotension was managed by a predefined protocol. The primary outcome was the incidence of dopamine-dependent hypotension, defined as having received at least 6 µg/kg/min dopamine for at least 24 hours during postnatal days 4-7.

Results: As expected, the incidence of moderate-to-large PDA at the end of the first week differed significantly between epochs (PINDO = 8%; conservative = 64%). In multivariate analyses, infants in the PINDO epoch had a significantly lower incidence of vasopressor-dependent hypotension (11%) than infants in the conservative epoch (21%; OR = 0.40, 95% CI 0.20-0.82). Infants in the PINDO epoch also required less mean airway pressure, had a lower respiratory severity score, and lower mode of ventilation score than infants in the conservative epoch during postnatal days 4-7. The effects of PINDO on both the incidence of vasopressor-dependent hypotension and the need for respiratory support were no longer significant when analyses were adjusted for "presence or absence of a moderate-to-large PDA."

Conclusion: PINDO decreases vasopressor-dependent hypotension and the need for respiratory support at the end of the first postnatal week. These effects are mediated by closure of the PDA.

Keywords: dopamine; hypotension; newborn; premature birth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Agents / therapeutic use*
  • Cohort Studies
  • Dopamine / therapeutic use*
  • Ductus Arteriosus, Patent / complications
  • Ductus Arteriosus, Patent / drug therapy*
  • Ductus Arteriosus, Patent / epidemiology
  • Echocardiography
  • Female
  • Humans
  • Hypotension / drug therapy
  • Hypotension / epidemiology*
  • Hypotension / etiology
  • Incidence
  • Indomethacin / therapeutic use*
  • Infant, Extremely Premature
  • Infant, Newborn
  • Male
  • Retrospective Studies

Substances

  • Cardiovascular Agents
  • Dopamine
  • Indomethacin