Opioid Free anesthesia in cardiac surgery: The OFACAR randomized clinical trial

Background: Opioid-free anesthesia (OFA) may reduce postoperative complications in cardiac surgery, but evidence from large randomized trials is limited. Methods: We conducted a randomized, controlled, blinded, multicenter superiority trial at two tertiary university hospitals in France from August 2021 to December 2023. We enrolled 320 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either OFA (n=159) consisting of intravenous ketamine, dexamethasone, lidocaine, and magnesium sulfate, or opioid anesthesia with sufentanil (n=161). The primary outcome was a composite of postoperative neurological, respiratory, cardiovascular, renal complications, and/or death within 30 days after surgery. Results: Among 320 participants (mean age 66.4 ± 10.5 years; 247 men [77.2%]), the primary outcome occurred in 120 patients (75.4%) in the OFA group compared with 136 patients (84.5%) in the control group (Risk Ratio [RR], 0.90; 95% confidence interval [CI], 0.80-0.99; P = 0.049). The fragility index for the primary outcome was 1. OFA was associated with significant reductions in cardiovascular complications (64.2% vs. 75.2%; RR, 0.86; 95% CI, 0.74-0.99; P = 0.031), particularly postoperative myocardial damage (61.6% vs. 72.1%), and digestive complications (2.5% vs. 11.2%; RR, 0.22; 95% CI, 0.08-0.65; P = 0.007). No death occurred in the OFA group compared with 6 patients in the control group (P=0.014). Conclusions: In patients undergoing cardiac surgery with cardiopulmonary bypass, opioid-free anesthesia may reduce composite postoperative complications compared with opioid anesthesia. The primary endpoint composite fragility index indicate that these results should be considered hypothesis-generating and warrant confirmation in larger trials. Trial registration: NCT04886453