Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants: a study protocol for a randomized controlled trial

Trials. 2018 Jun 13;19(1):318. doi: 10.1186/s13063-018-2705-5.

Abstract

Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement.

Methods: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36 months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%.

Discussion: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36 months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36 months old.

Trial registration: Dutch Trial Registry ( www.trialregister.nl ): NTR5448 on September 1, 2015. Institutional review board approval (MEC2015-646), current protocol version: July 3, 2017.

Keywords: Pain, Sedation, Opioids, Children, Intensive care, Cardiac surgery, PK, PD.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Acetaminophen / administration & dosage*
  • Acetaminophen / adverse effects
  • Administration, Intravenous
  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Belgium
  • Cardiac Surgical Procedures* / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / surgery*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Morphine / administration & dosage*
  • Morphine / adverse effects
  • Multicenter Studies as Topic
  • Pain Measurement
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Treatment Outcome

Substances

  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Acetaminophen
  • Morphine

Grants and funding