Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial

BMJ. 2021 Jun 2:373:n1162. doi: 10.1136/bmj.n1162.

Abstract

Objective: To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery.

Design: Phase III, randomised, double blind, placebo controlled trial.

Setting: 34 centres in France, December 2017 to March 2019.

Participants: 1222 adults (>50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months.

Interventions: Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure.

Main outcomes measures: The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered).

Results: Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46).

Conclusions: Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness.

Trial registration: ClinicalTrials.gov NCT03218553.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Pragmatic Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / administration & dosage*
  • Dexamethasone / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • France
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Operative Time
  • Postoperative Care
  • Postoperative Complications / mortality*
  • Postoperative Complications / prevention & control*

Substances

  • Anti-Inflammatory Agents
  • Dexamethasone

Associated data

  • ClinicalTrials.gov/NCT03218553