Restricting Intraoperative Benzodiazepines During Cardiac Surgery Does Not Significantly Reduce Delirium

In a cluster randomized crossover trial including nearly 20,000 patients undergoing open cardiac surgery, an institutional policy of restricting intraoperative benzodiazepine use during cardiac anesthesia was not associated with a statistically significant reduction in postoperative delirium. According to the results of the study, published in JAMA Surgery, delirium occurred in 14.0% of patients during restricted periods and 14.9% during liberal periods.

Delirium is a common and serious postoperative complication following cardiac surgery, associated with prolonged hospital stays, cognitive decline, and increased mortality. Benzodiazepines have long been suspected to contribute to postoperative delirium, but according to the study authors, no randomized trial has previously assessed whether restricting their use during surgery reduces this risk.

This multiperiod, cluster randomized crossover trial was conducted at 20 North American cardiac surgery centers between November 2019 and December 2022. Adult patients (n = 19,768) undergoing open cardiac surgery were enrolled through a waiver of individual consent. Centers were randomized to implement either a restrictive or liberal intraoperative benzodiazepine policy for alternating 4-week periods, with 12 to 18 crossovers occurring at each site over the study duration. The primary outcome was incidence of delirium within 72 hours postoperatively, assessed using either the Confusion Assessment Method–Intensive Care Unit or the Intensive Care Delirium Screening Checklist.

Of the 19,768 patients, 9827 underwent surgery during restricted periods and 9941 during liberal periods. The mean age of the patients was 65 years, and 73.5% of the cohort were men. Adherence to policy was high in both arms (90.9% in restricted periods vs 93.2% in liberal periods). Delirium incidence did not differ significantly between groups (P = .07), though there was a trend toward reduced delirium with benzodiazepine restriction. Additionally, no patients reported intraoperative awareness, indicating the restrictive policy did not compromise intraoperative sedation.

“Given that smaller effect sizes cannot be ruled out, restriction of benzodiazepines during cardiac surgery may be considered,” the authors concluded. “Research is required to determine whether restricting intraoperative benzodiazepines at the patient level can reduce the incidence of postoperative delirium.”

Reference
Spence J, Devereaux PJ, Lee SF, et al. Benzodiazepine-free cardiac anesthesia for reduction of postoperative delirium: a cluster randomized crossover trial. JAMA Surg. 2025;160(3):286-294. doi:10.1001/jamasurg.2024.6602