Reassessing pharmacologic amnesia: benzodiazepines and intraoperative awareness in adults: a perspective on the limits of the evidence and the primacy of anesthetic depth

Perioperative benzodiazepines (BZDs) have long been given to adults in part for their anterograde amnestic effect: a pharmacologic safety net intended to prevent explicit memories of intraoperative awareness, should it occur. Recent evidence calls for a reassessment of that rationale, though not for its abandonment. In the 2025 B-Free trial (n = 19,768), a cluster-randomized crossover trial in adult cardiac surgery, no patient in either the BZD-free or the BZD-liberal group spontaneously reported awareness. Awareness is rare, however, and the trial ascertained it by spontaneous report rather than structured interview, so this observation says little about small or infrequent effects. The trial was powered for postoperative delirium. Its primary intention-to-treat analysis was neutral (14.0% vs 14.9%; adjusted odds ratio 0.92, 95% confidence interval 0.84 to 1.01; P = 0.07). A per-protocol analysis suggested lower odds of delirium (odds ratio 0.90, 95% confidence interval 0.82 to 0.99; P = 0.02), an exploratory result open to selection and adherence bias. Systematic reviews and randomized trials do not establish a reliable awareness-preventive benefit of routine BZD administration, and several suggest possible harm. We argue that prevention of intraoperative awareness should rest on the assurance of adequate anesthetic depth, supported by preoperative risk stratification, monitoring beyond vital signs, and protocolized depth management. We also set out the principal limitations of the evidence base.