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

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.