Dexamethasone for Patients Undergoing Major Noncardiac Surgery: A Multicenter, Double-Blind, Controlled Randomized Trial

Background: Surgery initiates inflammation which contributes to postoperative morbidity and mortality. We aim ed to assess the effects of dexamethasone on postoperative complications in patients undergoing major surgery. Methods: In a multicenter, randomized, double-blind trial, patients over 50 years of age undergoing non-cardiac surgery with expected duration of more than 90 minutes were recruited from 34 centers. We randomly assigned patients to dexamethasone (0·2 mg.kg-1 after the procedure, and on day+1) or to placebo. Randomization was stratified on two criteria: cancer and thoracic procedure. The primary outcome was a composite of major complications and all-cause mortality assessed: i) in the intention-to-treat population (ITT) with multiple imputation methods for missing data and adjusted on stratification factors and center as random effect and ii) in the modified intention to treat population. Findings: Of the 1,222 patients enrolled from the 13th of December 2017 through the 19th of February 2019, 613 patients were randomized to dexamethasone, and 609 to placebo in ITT. 104 patients (17.1%) in the dexamethasone group and 123 patients (20 · 4%) in the placebo group had major complications or died within 14 days after surgery (adjusted odds ratio, 0 · 78; 95% confidence interval [CI], 0 · 59-1 · 04; P=0 · 09, crude odds ratio 0 · 79; 95%CI, 0 · 60-1 · 07, P=0 · 13). In the stratum of patients having non-thoracic surgery (n=1061 patients), the adjusted odd ratio of primary outcome with dexamethasone was 0 · 71 (95%CI 0 · 53-0 · 96). The adjusted hazard ratio with dexamethasone for mechanical ventilation was 0 · 68 (95%CI 0 · 53-0 · 88, P=0 · 003). Adverse events were reported in 47% and 48 · 6% of patients who received dexamethasone or placebo (odd ratio: 0 · 92; 95%CI 0 · 74-1 · 15, P=0 · 46). Interpretation: After major non-cardiac surgery, dexamethasone did not result in significantly less mortality or fewer major complications 14 days after surgery. Trial Registration: The trial was registered with clinicaltrial.gov NCT03218553. Funding Statement: Funded by French Ministry of Health, PHRCN 2016, RC16_0442. Declaration of Interests: Dr Asehnoune reports receiving lecture fees from Baxter, Fisher & Paykel, LFB and consulting fees from Edward Lifesciences, LFB. Dr. Boisson reports receiving consulting fees from BD. Dr. Jaber reports receiving personal fees from Drager, Medtronic, Baxter, Medtronic and Fisher & Paykel, Fresenius-Xenios. Dr Leone reports receiving consulting fees from Aspen, Orion, MSD, Pfizer, 3M, Octapharma and Edward. Dr Futier reports receiving consulting fees from Drager Medical, GE Healthcare, Edwards Lifesciences, and Orion Pharma and lectures fees from Fresenius Kabi, Baxter and Fisher & Paykel. Dr. Roquilly reports receiving consulting fees from Merck and bioMerieux. Other authors declare that they have no conflicts of interest involving the work under consideration for publication. No compensation was received for this study. Ethics Approval Statement: The PACMAN trial was approved in June 2017 by an institutional review board (Sud Mediterranee V) and was conducted in accordance with the Declaration of Helsinki. Patients provided written informed consent before participation.