Exemplar Trial Overview - B-Free. (18-min video & 27-slide presentation)

• Summary: Existing evidence suggests that patients receiving benzodiazepines in the intensive care unit after cardiac surgery may be at elevated risk of delirium; postoperative delirium is associated with increased morbidity, mortality, and health care costs. Dr. Jessica Spence overviews the Benzodiazepine-Free Cardiac Anesthesia (B-Free) pragmatic, multiple-period, cluster randomized crossover trial (Nov. 2019 - Dec. 2022) to determine whether an institutional policy of restricted intraoperative benzodiazepine administration, compared to a policy of liberal use, would reduce the incidence of delirium after cardiac surgery.

Spence J, et al. Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial. JAMA Surg. 2025 Mar 1;160(3):286-294. Erratum in: JAMA Surg. 2025 May 1;160(5):604. (9-page paper)

• Summary: Delirium is common after cardiac surgery, and it is associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial. This publication in JAMA Surgery describes the B-Free pragmatic, multiperiod, patient- and assessor-blinded, cluster randomized crossover trial. This trial took place at 20 North American cardiac surgical centres and answered the question: “Does an institutional policy restricting benzodiazepines during cardiac anesthesia reduce the incidence of postoperative delirium?”

Exemplar Trial - B-Free. (13-min video & 15-slide presentation)

• Summary: Dr. Jessica Spence breaks down the B-Free pragmatic trial across sections of the curriculum wheel.

Spence J, et al. JAMA Surgery Visual Abstract. JAMA Surg. 2025 Mar 1;160(3):286-294. (1-page image)

• Summary: An image summarizing the population, settings/locations, intervention, primary outcome, and findings of the B-Free trial.

Spence J, et al. The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial. Can J Anaesth. 2018 Jul;65(7):813-821. (9-page paper)

• Summary: Uses the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial to discuss the concept of randomized cluster crossover trials as a means of answering research questions related to comparative effectiveness in anesthesia.

Spence J, et al. Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial. CJC Open. 2023 Jun 8;5(9):691-699. (9-page paper)

• Summary: A clinical trial protocol describing the Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial, a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration, as compared with a policy of liberal intraoperative benzodiazepine administration, reduces delirium.

Spence J, et al. Restricted versus liberal intraoperative benzodiazepine use in cardiac anaesthesia for reducing delirium (B-Free Pilot): a pilot, multicentre, randomised, cluster crossover trial. Br J Anaesth. 2020 Jul;125(1):38-46. (9-page paper)

• Summary: A two-centre, pilot, randomized cluster crossover trial (with four 4-week crossover periods) to inform the feasibility of a large randomized cluster crossover trial (the B-Free trial) which examined whether an institutional policy of restricted benzodiazepine administration during cardiac surgery (compared with liberal administration) would reduce delirium.

Critical Care Reviews Podcast - B-Free Trial (with Dr. Jessica Spence - April 7, 2024): 41-min podcast.

• Summary: Dr. Rob Mac Sweeney discusses the B-Free trial with Dr. Jessica Spence on the Critical Care Reviews podcast. 

Kleiman, AM, et al. Benzodiazepines Not Main Suspect in Cardiac Surgery Delirium. JAMA Surg. 2025 160(3):294-295. (2-page commentary)

• Summary: A brief invited commentary on the B-Free trial.

Spence J, et al. Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free). ClinicalTrials.gov identifier: NCT03928236. Updated 2025-03-04. (8-section website)

• Summary: Public registration of the trial (i.e., study overview, contacts and locations, study plan, collaborators and investigators, publications, study record dates).