Opioid-free cardiac anaesthesia: a positive trial that says so itself with caution

Design

randomised, controlled, blinded, multicentre superiority trial, two French tertiary hospitals, 2021-2023

Population

320 adults undergoing elective cardiac surgery with cardiopulmonary bypass, mean age 66.4 years, 77.2% men

Primary outcome

composite of neurological, respiratory, cardiovascular or renal complications, or death, within 30 days

Effect

75.4% vs 84.5%, RR 0.90 (95% CI 0.80 to 0.99), P = 0.049; fragility index 1

OFACAR randomised 320 adults having elective cardiac surgery with cardiopulmonary bypass at two French tertiary hospitals to an opioid-free technique — intravenous ketamine, dexamethasone, lidocaine and magnesium sulfate — or to sufentanil. The primary endpoint was a 30-day composite of neurological, respiratory, cardiovascular or renal complications, or death. It occurred in 75.4% of the opioid-free group and 84.5% of the control group (RR 0.90, 95% CI 0.80 to 0.99, P = 0.049).

The honest reading is in the fragility index, which was 1. One patient moving between groups would have taken the result across the line into non-significance. The investigators say plainly that the finding is hypothesis-generating and needs a larger trial. Two component results are harder to dismiss: digestive complications fell from 11.2% to 2.5% (RR 0.22, 95% CI 0.08 to 0.65), and there were no deaths in the opioid-free arm against six in the control arm.

So this is not yet a reason to rewrite a cardiac anaesthesia protocol, but it is a reason to stop treating opioid-free technique in this population as unproven in principle. The event rate is the striking number: more than three-quarters of patients in both arms met the composite. A composite that common is easy to move and hard to interpret, and the mortality and gastrointestinal signals deserve a trial powered to test them directly.

• Record which components of any composite you are actually trying to prevent before adopting a technique on composite evidence
• If trialling the regimen, the tested combination was ketamine, dexamethasone, lidocaine and magnesium sulfate — not any opioid-sparing mixture
• Watch postoperative ileus and gastrointestinal recovery, where the largest single effect sat
• Baseline complication rates above 75% mean your own case mix may behave differently; audit locally before and after
• Blinded but two-centre and elective only — do not extend to emergency or redo bypass surgery on this evidence

The statistics, in plain English

A fragility index of 1 means the entire result rests on a single patient's outcome; had one more opioid-free patient had a complication, P would have exceeded 0.05. The upper confidence limit of 0.99 sits almost exactly on no effect, so the data are compatible with a benefit anywhere from substantial to negligible. The mortality difference (0 vs 6) was not the primary endpoint and comes from small numbers, so it is a signal to test rather than an effect size to quote.

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