Postoperative delirium incidence is not reduced while restricting benzodiazepines during cardiac surgery, according to an intention-to-treat analysis. However, an analysis of patients treated according to policy showed an approximate 10% reduction in delirium after cardiac surgery with restricted benzodiazepine use during surgery, a new randomized trial shows. These data were presented by Jessica Spence, MD, PhD, of the Population Health Research Institute, Hamilton, Ontario, in a Featured Clinical Research session Sunday at the American College of Cardiology (ACC) Scientific Sessions 2024 in Atlanta. Delirium impacts more than 15% of patients post-cardiac surgery and is considered an acute cognition disorder. These patients can develop post-traumatic stress disorder and exceed their predicted hospital stay by 13 days. Benzodiazepines before and after cardiac surgery are often used to treat this, but no trial has offered results on restricting benzodiazepines. The investigators in the B-FREE trial sought to show the 72-hour post-operative effects of restricting benzodiazepine use on cardiac surgery patients. This multi-period, cluster, randomized, multi-center, crossover study compared liberal versus restrictive use of benzodiazepines in patients who underwent cardiac surgery at 20 hospitals in Canada and the U.S. through 12 to 18 four-week crossover periods. Hospitals were randomized to liberal or restrictive use. Restricted use was defined as no routine administration of benzodiazepines. Liberal use was defined as ≥0.03 mg/kg midazolam equivalent administered. The primary outcome of the study was delirium up to 72 hours post-cardiac surgery. The safety outcome was intraoperative awareness. The post hoc outcome was the number of positive delirium assessments. A total of 19,768 patients (mean age=64.9 years, 26.5% male) underwent cardiac surgery (9,827 restrictive and 9,941 liberal). The policy was applied to 90.9% of restrictive period patients and 93.2% of liberal period patients, with a total adherence to policy rate of 92%. Nearly half (49%) of the surgical procedures were isolated coronary artery bypass graft, and the second most common procedure was isolated valvular surgery (17%). Emergency surgery was performed in 7.8% of trial patients. In the restrictive group, 14% of patients had delirium within 72 hours. In the liberal group, 14.9% of patients had delirium within 72 hours (adjusted odds ratio=0.92, 95% confidence interval [CI]=0.84-1.01; p=0.07). When only patients who were treated according to policy were analyzed, 13.7% of patients in the restrictive group experienced delirium within 72 hours and 14.8% of patients in the liberal group experienced delirium within 72 hours (adjusted risk ratio [aRR]=0.90; 95% CI=0.82-0.99; p=0.02). The difference in postoperative delirium was even more pronounced when patients managed according to policy were analyzed excluding those from the restrictive arm who had received benzodiazepine within 24 hours of surgery (restrictive 13.4% vs. liberal 14.8%; aRR=0.87; 95% CI: 0.79-0.96; p=0.005). Overall, in the intention-to-treat analysis, a restricted benzodiazepine policy did not reduce postoperative delirium. However, when only the on-policy patients were analyzed, there was a 10% reduction in delirium with restrictive benzodiazepine use, and the difference was even larger when all benzodiazepine exposure within 24 hours before surgery was eliminated. The investigators recommended the consideration of restricting benzodiazepines during cardiac surgery. Photo Credit: Jason Wermers/CRTonline.org Photo Caption: Jessica Spence, MD, PhD, presents results from the B-FREE trial Sunday at ACC.24