In the Literature

Summary of "Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial"

Summary published January 26, 2026

Summary by Jeffrey Huang, MD, FASA

JAMA Surgery | March 2025

Spence J, Devereaux PJ, Lee SF, D'Aragon F, Avidan MS, Whitlock RP, Mazer CD, Rousseau-Saine N, Rajamohan RR, Pryor KO, Klein R, Tan E, Cameron MJ, Di Sante E, DeBorba E, Mustard ME, Couture EJ, Zamper RPC, Law MWY, Djaiani G, Saha T, Choi S, Hedlin P, Pikaluk DR, Lam W, Deschamps A, Ramasundarahettige CF, Vincent J, McIntyre WF, Oczkowski SJW, Dulong BJ, Beaver C, Kloppenburg SA, Lamy A, Jacobsohn E, Belley-Côté EP; B-Free Investigators and the Canadian Perioperative Anesthesia Clinical Trials Group. Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial. JAMA Surg. 2025 Mar 1;160(3):286-294. doi: 10.1001/jamasurg.2024.6602. Erratum in: JAMA Surg. 2025 May 1;160(5):604. doi: 10.1001/jamasurg.2025.0799. Erratum in: JAMA Surg. 2026 Jan 1;161(1):104. doi: 10.1001/jamasurg.2025.5476. PMID: 39878960; PMCID: PMC11780505.

doi: https://doi.org/10.1001/jamasurg.2024.6602

  • Cardiac surgery is associated with a high incidence of postoperative delirium.
  • Perioperative benzodiazepine administration may also be associated with postoperative delirium, yet the majority of patients undergoing cardiac surgery receive benzodiazepines under the belief that these medications reduce intraoperative awareness.
  • In this pragmatic, multiperiod, patient-and assessor-blinded, cluster randomized crossover trial, the authors sought to determine whether an institutional policy of restricted intraoperative benzodiazepine administration, compared with liberal use, would reduce the incidence of postoperative delirium following cardiac surgery.
  • 20 North American cardiac surgical centers were randomized to implement either a restricted or liberal benzodiazepine policy during twelve to eighteen 4-week crossover periods.
  • The restricted policy prohibited benzodiazepine administration during cardiac surgery, while the liberal policy mandated administration of at least 0.03 mg/kg ideal body weight of midazolam equivalent during surgery.
  • The primary outcome was the incidence of postoperative delirium within 72 hours of surgery, as assessed during routine clinical care with either the Confusion Assessment Method–ICU or the Intensive Care Delirium Screening Checklist.
  • Secondary outcomes included ICU length of stay, hospital length of stay, and all-cause in-hospital mortality.
  • 19,768 patients met inclusion criteria (mean age 65 +/- 12 years), with 9,827 undergoing surgery during restricted periods and 9,941 during liberal periods.
  • Delirium occurred in 14.0% of patients during restricted periods and 14.9% during liberal periods (adjusted odds ratio 0.92; 95% CI, 0.84–1.01; P = .07). ICU length of stay did not differ between groups (adjusted mean difference 0.04 days; 95% CI, −0.12 to 0.27; P = .68).
  • No incidents of intraoperative awareness were reported in either group.
  • The authors suggested that restricting the administration of intraoperative benzodiazepine use did not significantly reduce the incidence of delirium within 72 hours following cardiac surgery.
  • However, the authors note that a small effect size could not be ruled out, and that further research is needed to determine whether benzodiazepine restriction at the patient level (rather than the institutional level) might reduce the risk of postoperative delirium after cardiac surgery.