Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium
Authors: Jessica Spence, P. J. Devereaux, Shun-Fu Lee, Frédérick D’Aragon, Michael S. Avidan, Richard P. Whitlock, C. David Mazer, Nicolas Rousseau-Saine, Raja Ramaswamy Rajamohan, Kane O. Pryor, Rael Klein, Edmund Tan, Matthew J. Cameron, Emily Di Sante, Erin DeBorba, Mary E. Mustard, Etienne J. Couture, Raffael Pereira Cezar Zamper, Michael W. Y. Law, George Djaiani, Tarit Saha, Stephen Choi, Peter Hedlin, D. Ryan Pikaluk, Wing Lam, Alain Deschamps, Chinthanie F. Ramasundarahettige, Jessica Vincent, William F. McIntyre, Simon J. W. Oczkowski, Braden J. Dulong, Christopher Beaver, Shelley A. Kloppenburg, Andre Lamy, Eric Jacobsohn, Emilie P. Belley-Côté, George Wyse, John Eikelboom, Tara Robinson, Gladys Marfo, Kumar Balasubramanian, Peter Koh, Courtney Mullen, Leah Hayward, Matthew Ryan McFarling, Kim Botsford, Summer Syed, Maia Shen, Renée Fournier, Morvarid Kavosh, Kate MacKenzie, Marita Monterola, Linda Girling, Mathilde St-Pierre, Michel-Antoine Perreault, Étienne de Medicis, Jonathan Gaulin, Nicola Edward, Ron Ree, Iris Yao, Clement Chui, Michelle Biferie, Connie Game, Juliet Ann Atherstone, Darren Mullane, Juliet Atherstone, Michelle Mozel, Mikaela Barton, Ashlee Hughes, Aiman Hasnat, Ramiro Arellano, Robert Tanzola, Debbie DuMerton, Michael Cummings, Ahmad Alli, Samson Moses, Niloufar Siadati-Fini, Kyle Chin, Greg Hare, Maliha Muneer, Izabela M Panek, Kaela H Fraser, Flynn A Bonazza, Sharon E Amey, Shelley Roulston, Sophie Robichaud, Marco Julien, Antoine Rochon, Marie-Eve Chamberland, Meggie Raymond, Jennifer Cogan, Georges Desjardins, Jean-Sébastien Lebon, Christian Ayoub, Pierre Couture, Athanase Courbe, Maria Rosal Martins, André Y Denault, An Ni Wu, Kristofer Beggs, Stéphanie Jarry, Sarah Bendaoud, Ester Cisneros-Aguilera, Lana Agoian, Melissa Laurendeau, Elaine Duval, Anya Chabane, Martine Lacroix, Liam J Kennedy, Robert Christopher Mayer, Michelle Clunie, Azeez Akinlade, Hugo Tremblay, Nathalie Gagné, Annie Bergeron, François Laforge, Audrey Grenier, Valérie Morin, Sandrine Bellavance, Valérie Lafrenière-Bessi, Béatrice Martin, Joanie Lachance, Olivier Audet, Léa Vachon-Zicat, Yasmine Babaki, Élizabeth St-Onge, Nelson Lavoie, Mathilde Bisson, Marie-Ève Charest, Angela Jerath, Lilia Kaustov, Andrew Fleet, Sophia Wong, Elizabeth Lappin, Saba Shaheen, Mohammad Helwani, Thaddeus Budelier, Arianna Montes de Oca, Alex Kronzer, Meghann M Fitzgerald, Natalia I Girardi, Leonard N Girardi, Michele L Steinkamp, Lisbeth A Evered, Hannah R Leibowitz, Dylan R Bitensky, Lisbeth Evered, Alexis Turgeon, André Denault, Daniel McIssac, Kathryn Sparrow, Manoj Lalu, Stuart McCluskey, Richard Hall, William Scott Beattie
Journal: JAMA Surgery (2025)

Importance Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial. Objective To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium. Design, Setting, and Participants This pragmatic, multiperiod, patient- and assessor-blinded, cluster randomized crossover trial took place at 20 North American cardiac surgical centers. All adults undergoing open cardiac surgery at participating centers during the trial period were included through a waiver of individual patient consent between November 2019 and December 2022. Intervention Institutional policies of restrictive vs liberal intraoperative benzodiazepine administration were compared. Hospitals (clusters) were randomized to cross between the restricted and liberal benzodiazepine policies 12 to 18 times over 4-week periods. Main Outcomes and Measures The primary outcome was the incidence of delirium within 72 hours of surgery as detected in routine clinical care, using either the Confusion Assessment Method–Intensive Care Unit or the Intensive Care Delirium Screening Checklist. Intraoperative awareness by patient report was assessed as an adverse event. Results During the trial, 19 768 patients (mean [SD] age, 65 [12] years; 14 528 [73.5%] male) underwent cardiac surgery, 9827 during restricted benzodiazepine periods and 9941 during liberal benzodiazepine periods. During restricted periods, clinicians adhered to assigned policy in 8928 patients (90.9%), compared to 9268 patients (93.2%) during liberal periods. Delirium occurred in 1373 patients (14.0%) during restricted periods and 1485 (14.9%) during liberal periods (adjusted odds ratio [aOR], 0.92; 95% CI, 0.84-1.01; P = .07). No patient spontaneously reported intraoperative awareness. Conclusions and Relevance In intention-to-treat analyses, restricting benzodiazepines during cardiac surgery did not reduce delirium incidence but was also not associated with an increase in the incidence of patient-reported intraoperative awareness. Given that smaller effect sizes cannot be ruled out, restriction of benzodiazepines during cardiac surgery may be considered. Research is required to determine whether restricting intraoperative benzodiazepines at the patient level can reduce the incidence of postoperative delirium. Trial Registration ClinicalTrials.gov Identifier: NCT03928236