Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

Fetal Diagn Ther. 2019;45(5):339-344. doi: 10.1159/000491748. Epub 2018 Aug 29.

Abstract

Introduction: The use of perioperative tocolytic agents in fetal surgery is imperative to prevent preterm labor. Indomethacin, a well-known tocolytic agent, can cause ductus arteriosus (DA) constriction. We sought to determine whether a relationship exists between preoperative indomethacin dosing and fetal DA constriction.

Materials and methods: This is an IRB-approved, single-center retrospective observational case series of 42 pregnant mothers who underwent open fetal myelomeningocele repair. Preoperatively, mothers received either 1 (QD) or 2 (BID) indomethacin doses. Maternal anesthetic drug exposures and fetal cardiac dysfunction measures were collected from surgical and anesthesia records and intraoperative fetal echocardiography. Pulsatility Index was used to calculate DA constriction severity. Comparative testing between groups was performed using t- and chi-square testing.

Results: DA constriction was observed in all fetuses receiving BID indomethacin and in 71.4% of those receiving QD dosing (p = 0.0002). Severe DA constriction was observed only in the BID group (35.7%). QD indomethacin group received more intraoperative magnesium sulfate (p < 0.0001). Minimal fetal cardiac dysfunction (9.5%) and bradycardia (9.5%) were observed in all groups independent of indomethacin dosing.

Conclusions: DA constriction was the most frequent and severe in the BID indomethacin group. QD indomethacin and greater magnesium sulfate dosing was associated with reduced DA constriction.

Keywords: Bradycardia; Cardiac dysfunction; Doppler; Ductus arteriosus; Fetal surgery; Indomethacin; Magnesium sulfate; Myelomeningocele.

Publication types

  • Observational Study

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Constriction
  • Dose-Response Relationship, Drug
  • Ductus Arteriosus / diagnostic imaging
  • Ductus Arteriosus / drug effects
  • Ductus Arteriosus / surgery*
  • Female
  • Fetal Therapies / methods*
  • Humans
  • Indomethacin / administration & dosage*
  • Meningomyelocele / diagnostic imaging
  • Meningomyelocele / drug therapy
  • Meningomyelocele / surgery*
  • Pregnancy
  • Retrospective Studies
  • Tocolytic Agents / administration & dosage*
  • Ultrasonography, Prenatal / methods

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Tocolytic Agents
  • Indomethacin