BACKGROUND: Opioid-free anesthesia (OFA) may reduce postoperative complications in cardiac surgery, but evidence from large randomized trials is limited.

METHODS: This study was a randomized, controlled, blinded, multicenter superiority trial at two tertiary university hospitals in France from August 2021 to December 2023. The study 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 neurologic, respiratory, cardiovascular, or renal complications and/or death within 30 days after surgery.

RESULTS: Among 320 participants (mean age, 66.4 ± 10.5 yr; 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% CI, 0.80 to 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 to 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 to 0.65; P = 0.007). No death occurred in the OFA group compared with six deaths 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 indicates that these results should be considered hypothesis generating and warrant confirmation in larger trials.

Anesthesiology rater

This well-conducted multi-centre RCT of 320 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass compared opioid-free anaesthesia (OFA) vs conventional anaesthesia with sufentanil infusion. The authors found a reduction in postoperative complications or death at 30 days (RR 0.90, 95% CI 0.80–0.99). There are several limitations. The primary outcome is a broad composite of complications, with the observed difference largely driven by cardiovascular ones. A low fragility index means that the primary finding is sensitive to small changes in event numbers. The OFA had 4 drugs, making it impossible to determine whether the observed effect is attributable to opioid avoidance or to components of the multimodal regimen. The comparator was also limited to sufentanil; the findings may not be generalisable to other opioids.

Anesthesiology rater

This is an interesting article and should be considered essential reading for cardiac anaesthetists. There are some issues with the conclusions, and I think that the between-group difference in mortality is likely by chance, as it seems too good to be true. I doubt whether these findings are likely to be reproduced, but all cardiac anaesthetists should read this and consider the implications.